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https://www.readbyqxmd.com/read/28743058/oral-nanotherapeutics-redox-nanoparticles-attenuate-ultraviolet-b-radiation-induced-skin-inflammatory-disorders-in-kud-hr-hairless-mice
#1
Chitho P Feliciano, Yukio Nagasaki
The active participation of an anti-inflammatory drug in the biological pathways of inflammation is crucial for the achievement of beneficial and therapeutic effects. This study demonstrated the development of redox nanoparticles that can circulate in the blood at significantly high levels, thus increasing their efficacy as an oral treatment against the deleterious effects of reactive oxygen species (ROS) in an in vivo inflammatory skin model. To confirm the blood bioavailability of the nanoparticles, mice were injected with the nanoparticles solution (RNP(N)) via oral gavage...
July 12, 2017: Biomaterials
https://www.readbyqxmd.com/read/28741687/a-distinct-plasma-lipid-signature-associated-with-poor-prognosis-in-castration-resistant-prostate-cancer-authors
#2
H-M Lin, K L Mahon, J M Weir, P A Mundra, C Spielman, K Briscoe, H Gurney, G Mallesara, G Marx, M R Stockler, PRIMe Consortium, R G Parton, A J Hoy, R J Daly, P J Meikle, L G Horvath
Lipids are known to influence tumour growth, inflammation, and chemoresistance. However, the association of circulating lipids with the clinical outcome of metastatic castration-resistant prostate cancer (CRPC) is unknown. We investigated associations between the plasma lipidome and clinical outcome in CRPC. Lipidomic profiling by liquid chromatography-tandem mass spectrometry was performed on plasma samples from a Phase 1 discovery cohort of 96 CRPC patients. Results were validated in an independent Phase 2 cohort of 63 CRPC patients...
July 25, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28739304/role-of-nadphox-rho-kinase-signaling-in-the-cyclosporine-nsaids-interactions-on-blood-pressure-and-baroreflexes-in-female-rats
#3
Hanan M El-Gowelli, Karim S Ibrahim, Ahmed F El-Yazbi, Mahmoud M El-Mas
AIMS: The hypertensive effect of the immunosuppressant drug cyclosporine (CSA) is paralleled, and probably triggered, by impaired arterial baroreceptor sensitivity (BRS). Here we asked if these effects of CSA are influenced by co-administration of nonsteroidal antiinflammatory drugs (NSAIDs) and if the oxidative NADPH-oxidase (NADPHox)/Rho-kinase (ROCK) pathway mediates this interaction. MATERIALS AND METHODS: Female rats were treated for 10days with CSA (25mg/kg/day), diclofenac (DIC, COX-1/COX-2 inhibitor, 1mg/kg/day), celecoxib (COX-2 inhibitor, 10mg/kg/day), or their combinations...
July 21, 2017: Life Sciences
https://www.readbyqxmd.com/read/28736231/serial-or-parallel-metastasis-of-cutaneous-melanoma-a-study-of-the-german-central-malignant-melanoma-registry
#4
Maximilian Gassenmaier, Thomas Kurt Eigentler, Ulrike Keim, Matthias Goebeler, Eckhard Fiedler, Gerold Schuler, Ulrike Leiter, Benjamin Weide, Eva-Maria Grischke, Peter Martus, Claus Garbe
For more than a century the Halstedian hypothesis of contiguous metastasis from the primary tumor through the lymphatics to distant sites shaped the lymph node surgery for melanoma. We challenge this dogma of serial metastatic dissemination. A single-center series of 2299 patients with cutaneous metastatic melanoma was investigated to analyze overall survival (OS) and distant metastasis-free survival (DMFS) of stage IV patients with or without primary lymphatic metastasis. Results were then compared with those of 2134 patients from three independent centers of the German Central Malignant Melanoma Registry...
July 20, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28732488/expression-of-the-scaffold-connector-enhancer-of-kinase-suppressor-of-ras-1-cnksr1-is-correlated-with-clinical-outcome-in-pancreatic-cancer
#5
Humair S Quadri, Taylor J Aiken, Michael Allgaeuer, Radim Moravec, Sean Altekruse, S Perwez Hussain, Markku M Miettinen, Stephen M Hewitt, Udo Rudloff
BACKGROUND: Despite the near universal occurrence of activating codon 12 KRAS somatic variants in pancreatic cancer, there is considerable heterogeneity in the molecular make-up, MAPK/ERK pathway activation states, and clinical outcome in this disease. We analyzed the expression levels of CNKSR1, a scaffold that influences MAPK/ERK pathway activity, in clinical pancreas cancer specimens and their impact on survival of patients with pancreatic cancer. METHODS: Immunohistochemical staining for CNKSR1 expression was performed on 120 specimens from three independent pancreatic cancer tissue registries, phospho-ERK levels were measured in 86 samples...
July 21, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28732309/zebularine-induces-replication-dependent-double-strand-breaks-which-are-preferentially-repaired-by-homologous-recombination
#6
Manuel Luis Orta, Nuria Pastor, Estefanía Burgos-Morón, Inmaculada Domínguez, José Manuel Calderón-Montaño, Carlos Huertas Castaño, Miguel López-Lázaro, Thomas Helleday, Santiago Mateos
Zebularine is a second-generation, highly stable hydrophilic inhibitor of DNA methylation with oral bioavailability that preferentially target cancer cells. It acts primarily as a trap for DNA methyl transferases (DNMTs) protein by forming covalent complexes between DNMT protein and zebularine-substrate DNA. It's well documented that replication-blocking DNA lesions can cause replication fork collapse and thereby to the formation of DNA double-strand breaks (DSB). DSB are dangerous lesions that can lead to potentially oncogenic genomic rearrangements or cell death...
July 12, 2017: DNA Repair
https://www.readbyqxmd.com/read/28729955/identification-of-four-prognostic-lncrnas-for-survival-prediction-of-patients-with-hepatocellular-carcinoma
#7
Zhonghao Wang, Qian Wu, Shu Feng, Yanhua Zhao, Chuanmin Tao
BACKGROUND: As the fifth most common cancer worldwide, Hepatocellular carcinoma (HCC) is also the third most common cause of cancer-related death in China. Several lncRNAs have been demonstrated to be associated with occurrence and prognosis of HCC. However, identification of prognostic lncRNA signature for HCC with expression profiling data has not been conducted yet. METHODS: With the reuse of public available TCGA data, expression profiles of lncRNA for 371 patients with HCC were obtained and analyzed to find the independent prognostic lncRNA...
2017: PeerJ
https://www.readbyqxmd.com/read/28729482/brca1-and-brca2-tumor-suppressors-protect-against-endogenous-acetaldehyde-toxicity
#8
Eliana Mc Tacconi, Xianning Lai, Cecilia Folio, Manuela Porru, Gijs Zonderland, Sophie Badie, Johanna Michl, Irene Sechi, Mélanie Rogier, Verónica Matía García, Ankita Sati Batra, Oscar M Rueda, Peter Bouwman, Jos Jonkers, Anderson Ryan, Bernardo Reina-San-Martin, Joannie Hui, Nelson Tang, Alejandra Bruna, Annamaria Biroccio, Madalena Tarsounas
Maintenance of genome integrity requires the functional interplay between Fanconi anemia (FA) and homologous recombination (HR) repair pathways. Endogenous acetaldehyde, a product of cellular metabolism, is a potent source of DNA damage, particularly toxic to cells and mice lacking the FA protein FANCD2. Here, we investigate whether HR-compromised cells are sensitive to acetaldehyde, similarly to FANCD2-deficient cells. We demonstrate that inactivation of HR factors BRCA1, BRCA2, or RAD51 hypersensitizes cells to acetaldehyde treatment, in spite of the FA pathway being functional...
July 20, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28726275/cpkc%C3%AE-mediated-down-regulation-of-uchl1-alleviates-ischaemic-neuronal-injuries-by-decreasing-autophagy-via-erk-mtor-pathway
#9
Dan Zhang, Song Han, Shizun Wang, Yanlin Luo, Li Zhao, Junfa Li
Stroke is one of the leading causes of death in the world, but its underlying mechanisms remain unclear. Both conventional protein kinase C (cPKC)γ and ubiquitin C-terminal hydrolase L1 (UCHL1) are neuron-specific proteins. In the models of 1-hr middle cerebral artery occlusion (MCAO)/24-hr reperfusion in mice and 1-hr oxygen-glucose deprivation (OGD)/24-hr reoxygenation in cortical neurons, we found that cPKCγ gene knockout remarkably aggravated ischaemic injuries and simultaneously increased the levels of cleaved (Cl)-caspase-3 and LC3-I proteolysis product LC3-II, and the ratio of TUNEL-positive cells to total neurons...
July 20, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28722677/prognostic-role-of-gli1-expression-in-breast-cancer-a-meta-analysis
#10
Bilan Wang, Ting Yu, Yuzhu Hu, Mengmeng Xiang, Haoning Peng, Yunzhu Lin, Lu Han, Lingli Zhang
Glioma-associated oncogene 1 (Gli1) is a critical transcriptional factor of Sonic hedgehog pathway which has been proved to participate in the initiation and progression of tumor in mammalians. However, its clinical value in breast cancer remains unknown. Thus, a meta-analysis was performed to clarify the association of Gli1 over-expression, clinic-pathological characteristics, molecular subtypes and prognosis in breast cancer. According to included criteria, 13 eligible studies containing 2816 patients all around the world were selected in this study...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722212/active-human-papillomavirus-involvement-in-barrett-s-dysplasia-and-oesophageal-adenocarcinoma-is-characterized-by-wild-type-p53-and-aberrations-of-the-retinoblastoma-protein-pathway
#11
Shanmugarajah Rajendra, Tao Yang, Wei Xuan, Prateek Sharma, Darren Pavey, Cheong Soon Lee, Son Le, Josephine Collins, Bin Wang
We have previously demonstrated that transcriptionally active high-risk HPV (hr-HPV) is strongly incriminated in Barrett's dysplasia (BD) and oesophageal adenocarcinoma (OAC) using mainly fresh frozen tissue. This study aimed to identify biomarkers of active HPV infection in Barrett's metaplasia, (BM)/BD/OAC by immunohistochemical staining (IHC) of formalin-fixed paraffin embedded (FFPE) tissue for aberrations of p53 and the retinoblastoma (pRb) pathway which are targets for the viral oncoproteins, E6/E7 respectively...
July 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28714850/high-resolution-mapping-of-heteroduplex-dna-formed-during-uv-induced-and-spontaneous-mitotic-recombination-events-in-yeast
#12
Yi Yin, Margaret Dominska, Eunice Yim, Thomas D Petes
In yeast, DNA breaks are usually repaired by homologous recombination (HR). An early step for HR pathways is formation of a heteroduplex, in which a single-strand from the broken DNA molecule pairs with a strand derived from an intact DNA molecule. If the two strands of DNA are not identical, there will be mismatches within the heteroduplex DNA (hetDNA). In wild-type strains, these mismatches are repaired by the mismatch repair (MMR) system, producing a gene conversion event. In strains lacking MMR, the mismatches persist...
July 17, 2017: ELife
https://www.readbyqxmd.com/read/28714573/assessment-of-the-dna-damaging-potential-of-environmental-chemicals-using-a-quantitative-high-throughput-screening-approach-to-measure-p53-activation
#13
Kristine L Witt, Jui-Hua Hsieh, Stephanie L Smith-Roe, Menghang Xia, Ruili Huang, Jinghua Zhao, Scott S Auerbach, Junguk Hur, Raymond R Tice
Genotoxicity potential is a critical component of any comprehensive toxicological profile. Compounds that induce DNA or chromosomal damage often activate p53, a transcription factor essential to cell cycle regulation. Thus, within the US Tox21 Program, we screened a library of ∼10,000 (∼8,300 unique) environmental compounds and drugs for activation of the p53-signaling pathway using a quantitative high-throughput screening assay employing HCT-116 cells (p53(+/+) ) containing a stably integrated β-lactamase reporter gene under control of the p53 response element (p53RE)...
July 17, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28714283/association-between-maternal-social-capital-and-infant-complementary-feeding-practices-in-rural-ethiopia
#14
Yunhee Kang, Jane Kim, Eunkyo Seo
Few studies have explored the potential of social capital in improving child nutritional status; however, most components of pathways between social capital and nutritional status have remained unexplained. Complementary feeding practice is a strong mediator of child nutritional status. This study examined the association between complementary feeding practice and maternal social capital in rural Ethiopia, using cross-sectional data of infant aged 6-12 months and their mother pairs (n = 870). The Short Social Capital Assessment Tool was used to assess maternal structural (i...
July 17, 2017: Maternal & Child Nutrition
https://www.readbyqxmd.com/read/28711786/exo1-suppresses-double-strand-break-induced-homologous-recombination-between-diverged-sequences-in-mammalian-cells
#15
Chun-Chin Chen, Elena Avdievich, Yongwei Zhang, Yu Zhang, Kaichun Wei, Kyeryoung Lee, Winfried Edelmann, Maria Jasin, Jeannine R LaRocque
DNA double-strand breaks (DSBs) can be repaired through several mechanisms, including homologous recombination (HR). While HR between identical sequences is robust in mammalian cells, HR between diverged sequences is suppressed by DNA mismatch-repair (MMR) components such as MSH2. Exonuclease I (EXO1) interacts with the MMR machinery and has been proposed to act downstream of the mismatch recognition proteins in mismatch correction. EXO1 has also been shown to participate in extensive DSB end resection, an initial step in the HR pathway...
July 10, 2017: DNA Repair
https://www.readbyqxmd.com/read/28704710/dissecting-the-biological-heterogeneity-within-hormone-receptor-positive-her2-negative-breast-cancer-by-gene-expression-markers-identifies-indolent-tumors-within-late-stage-disease
#16
Jyothi S Prabhu, Aruna Korlimarla, C E Anupama, Annie Alexander, Rohini Raghavan, Roma Kaul, Krisha Desai, Savitha Rajarajan, Suraj Manjunath, Marjorrie Correa, R Raman, Anjali Kalamdani, Msn Prasad, Shekar Patil, K S Gopinath, B S Srinath, T S Sridhar
Hormone receptor positive (HR+) breast cancers are a heterogeneous class with differential prognosis. Although more than half of Indian women present with advanced disease, many such patients do well. We have attempted identification of biologically indolent tumors within HR+HER2- tumors based on gene expression using histological grade as a guide to tumor aggression. 144 HR+HER2- tumors were divided into subclasses based on scores derived by using transcript levels of multiple genes representing survival, proliferation, and apoptotic pathways and compared to classification by Ki-67 labeling index (LI)...
July 11, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28704416/genetic-variation-in-the-eicosanoid-pathway-is-associated-with-non-small-cell-lung-cancer-nsclc-survival
#17
Lindsay N Sausville, Carissa C Jones, Melinda C Aldrich, William J Blot, Ambra Pozzi, Scott M Williams
Globally, lung cancer results in more deaths worldwide than any other cancer, indicating a need for better treatments. Members of the eicosanoid metabolism pathway represent promising therapeutic targets, as several enzymes involved in the generation of these lipids are dysregulated in many cancers and their inhibition reduces lung cancer growth in mouse models. However, genetic variation of enzymes involved in eicosanoid metabolism has not been adequately examined for association with lung cancer. The goal of this study was to determine whether germline genetic variation altering eicosanoid producing enzyme function and/or expression are associated with differences in lung cancer survival...
2017: PloS One
https://www.readbyqxmd.com/read/28699513/parp-inhibitor-drugs-in-the-treatment-of-breast-ovarian-prostate-and-pancreatic-cancers-an-update-of-clinical-trials
#18
Dalia Kamel, Christopher Gray, Jagdeeb Walia, Vikaash Kumar
PARP inhibitors appear to offer a promising role in the accompaniment of many of the cytotoxic agents used in the present day to combat cancer proliferation in BRCA1/2 deficient tumors. Current species of PARP inhibitors have yet to demonstrate a superior effect to that of existing therapies when administered as a single agent; however, they have appeared to amplify the effect of these existing chemotherapies when utilized together. This suggests that PARP inhibitors could play an effective maintenance role in current cancer-combating strategies...
July 11, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28698370/g9a-coordinates-with-the-rpa-complex-to-promote-dna-damage-repair-and-cell-survival
#19
Qiaoyan Yang, Qian Zhu, Xiaopeng Lu, Yipeng Du, Linlin Cao, Changchun Shen, Tianyun Hou, Meiting Li, Zhiming Li, Chaohua Liu, Di Wu, Xingzhi Xu, Lina Wang, Haiying Wang, Ying Zhao, Yang Yang, Wei-Guo Zhu
Histone methyltransferase G9a has critical roles in promoting cancer-cell growth and gene suppression, but whether it is also associated with the DNA damage response is rarely studied. Here, we report that loss of G9a impairs DNA damage repair and enhances the sensitivity of cancer cells to radiation and chemotherapeutics. In response to DNA double-strand breaks (DSBs), G9a is phosphorylated at serine 211 by casein kinase 2 (CK2) and recruited to chromatin. The chromatin-enriched G9a can then directly interact with replication protein A (RPA) and promote loading of the RPA and Rad51 recombinase to DSBs...
July 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28684452/lower-tsh-and-higher-free-thyroxine-predict-incidence-of-prostate-but-not-breast-colorectal-or-lung-cancer
#20
Yi Xian Chan, Matthew Knuiman, Mark L Divitini, Suzanne J Brown, John P Walsh, Bu Beng Yeap
CONTEXT: Thyroid hormones modulate proliferative, metabolic and angiogenic pathways, however few studies have examined associations of thyroid hormones with cancer risk. OBJECTIVES: To explore associations of thyrotropin (TSH), free thyroxine (FT4) and anti-thyroperoxidase antibodies (TPOAb) with the incidence of all (non-skin) cancers and specific common cancers. DESIGN AND SETTING: A prospective cohort study of a community-dwelling population aged 25-84 years in Western Australia...
July 6, 2017: European Journal of Endocrinology
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