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https://www.readbyqxmd.com/read/28525744/ctf4-prevents-genome-rearrangements-by-suppressing-dna-double-strand-break-formation-and-its-end-resection-at-arrested-replication-forks
#1
Mariko Sasaki, Takehiko Kobayashi
Arrested replication forks lead to DNA double-strand breaks (DSBs), which are a major source of genome rearrangements. Yet DSB repair in the context of broken forks remains poorly understood. Here we demonstrate that DSBs that are formed at arrested forks in the budding yeast ribosomal RNA gene (rDNA) locus are normally repaired by pathways dependent on the Mre11-Rad50-Xrs2 complex but independent of HR. HR is also dispensable for DSB repair at stalled forks at tRNA genes. In contrast, in cells lacking the core replisome component Ctf4, DSBs are formed more frequently, and these DSBs undergo end resection and HR-mediated repair that is prone to rDNA hyper-amplification; this highlights Ctf4 as a key regulator of DSB end resection at arrested forks...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28525417/assessing-frailty-in-patients-undergoing-destination-therapy-left-ventricular-assist-device-observations-from-interagency-registry-for-mechanically-assisted-circulatory-support
#2
Lauren B Cooper, Bradley G Hammill, Larry A Allen, JoAnn Lindenfeld, Robert J Mentz, Joseph G Rogers, Carmelo A Milano, Chetan B Patel, Karen P Alexander, Adrian F Hernandez
Frailty and heart failure share common pathways with symptoms that often coexist. Assessment of frailty may inform patient selection for left ventricular assist device (LVAD) therapy. Using Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) data of destination therapy (DT) LVAD patients from January 1, 2012, to March 31, 2014, we examined preimplantation provider-assessed frailty and gait speed testing and the association with 1 year postimplantation outcomes. Of 2,469 patients, 227 (9...
May 18, 2017: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
https://www.readbyqxmd.com/read/28524155/statin-use-candidate-mevalonate-pathway-biomarkers-and-colon-cancer-survival-in-a-population-based-cohort-study
#3
Ronan T Gray, Maurice B Loughrey, Peter Bankhead, Chris R Cardwell, Stephen McQuaid, Roisin F O'Neill, Kenneth Arthur, Victoria Bingham, Claire McGready, Anna T Gavin, Jacqueline A James, Peter W Hamilton, Manuel Salto-Tellez, Liam J Murray, Helen G Coleman
BACKGROUND: Statin use after colorectal cancer diagnosis may improve survival but evidence from observational studies is conflicting. The anti-cancer effect of statins may be restricted to certain molecular subgroups. In this population-based cohort study, the interaction between p53 and 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMGCR) expression, KRAS mutations, and the association between statin use and colon cancer survival was assessed. METHODS: The cohort consisted of 740 stage II and III colon cancer patients diagnosed between 2004 and 2008...
May 18, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28524096/itraq-mitoproteome-analysis-reveals-mechanisms-of-programmed-cell-death-in-arabidopsis-thaliana-induced-by-ochratoxin-a
#4
Yan Wang, Xiaoli Peng, Zhuojun Yang, Weiwei Zhao, Wentao Xu, Junran Hao, Weihong Wu, Xiao Li Shen, Yunbo Luo, Kunlun Huang
Ochratoxin A (OTA) is one of the most common and dangerous mycotoxins in the world. Previous work indicated that OTA could elicit spontaneous HR-like lesions formation Arabidopsis thaliana, reactive oxygen species (ROS) play an important role in OTA toxicity, and their major endogenous source is mitochondria. However, there has been no evidence as to whether OTA induces directly PCD in plants until now. In this study, the presence of OTA in Arabidopsisthaliana leaves triggered accelerated respiration, increased production of mitochondrial ROS, the opening of ROS-dependent mitochondrial permeability transition pores and a decrease in mitochondrial membrane potential as well as the release of cytochrome c into the cytosol...
May 18, 2017: Toxins
https://www.readbyqxmd.com/read/28523293/-triple-positive-breast-cancer-a-novel-category
#5
George Iancu, DănuŢ Vasile, Raluca Claudia Iancu, Dragoş Virgil DaviŢoiu
Breast cancer (BC) biology is of outmost importance for its therapeutic management and for establishing patients' outcome. Breast cancer has been divided in subtypes depending on the presence of hormone receptors (HRs) for estrogen and progesterone and human epidermal growth factor receptor 2 (HER2) gene amplification. Recently, a distinct subcategory has been analyzed from the group of HER2-enriched BC with positive HR, namely HER2 positive with high levels of hormone receptor expression, suggestively named "triple positive" breast cancer...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28523230/targeting-resolution-of-neuroinflammation-after-ischemic-stroke-with-a-lipoxin-a4-analog-protective-mechanisms-and-long-term-effects-on-neurological-recovery
#6
Kimberly E Hawkins, Kelly M DeMars, Jon C Alexander, Lauren G de Leon, Sean C Pacheco, Christina Graves, Changjun Yang, Austin O McCrea, Jan C Frankowski, Timothy J Garrett, Marcelo Febo, Eduardo Candelario-Jalil
BACKGROUND: Resolution of inflammation is an emerging new strategy to reduce damage following ischemic stroke. Lipoxin A4 (LXA 4) is an anti-inflammatory, pro-resolution lipid mediator that reduces neuroinflammation in stroke. Since LXA 4 is rapidly inactivated, potent analogs have been synthesized, including BML-111. We hypothesized that post-ischemic, intravenous treatment with BML-111 for 1 week would provide neuroprotection and reduce neurobehavioral deficits at 4 weeks after ischemic stroke in rats...
May 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28521962/the-functional-roles-of-pml-nuclear-bodies-in-genome-maintenance
#7
REVIEW
Hae Ryung Chang, Anudari Munkhjargal, Myung-Jin Kim, Seon Young Park, Eunyoung Jung, Jae-Ha Ryu, Young Yang, Jong-Seok Lim, Yonghwan Kim
In the nucleus, there are several membraneless structures called nuclear bodies. Among them, promyelocytic leukemia nuclear bodies (PML-NBs) are involved in multiple genome maintenance pathways including the DNA damage response, DNA repair, telomere homeostasis, and p53-associated apoptosis. In response to DNA damage, PML-NBs are coalesced and divided by a fission mechanism, thus increasing their number. PML-NBs also play a role in repairing DNA double-strand breaks (DSBs) by homologous recombination (HR). Clinically, the dominant negative PML-RARα fusion protein expressed in acute promyelocytic leukemia (APL) inhibits the transactivation of downstream factors and disrupts PML function, revealing the tumor suppressor role of PML-NBs...
May 5, 2017: Mutation Research
https://www.readbyqxmd.com/read/28521363/a-cisplatin-derivative-tetra-pt-bpy-as-an-oncotherapeutic-agent-for-targeting-alt-cancer
#8
Xiao-Hui Zheng, Xin Nie, Yiming Fang, Zepeng Zhang, Yingnan Xiao, Zongwan Mao, Haiying Liu, Jian Ren, Feng Wang, Lixin Xia, Junjiu Huang, Yong Zhao
Background: In approximately 15% of human cancers, telomere length is maintained independently of telomerase by the homologous recombination (HR)-mediated alternative lengthening of telomeres (ALT) pathway. Whether the ALT pathway can be exploited for therapeutic treatment remains unknown. The purpose of this study is to develop oncotherapeutic agent to target ALT cancers. Methods: Surface plasmon resonance assay, antibody to G-quadruplex, and fluorescence in situ hybridization (FISH) were used to discover Tetra-Pt(bpy), a cisplatin derivative that specifically targets telomeric G-quadruplex...
October 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28520779/church-attendance-allostatic-load-and-mortality-in-middle-aged-adults
#9
Marino A Bruce, David Martins, Kenrik Duru, Bettina M Beech, Mario Sims, Nina Harawa, Roberto Vargas, Dulcie Kermah, Susanne B Nicholas, Arleen Brown, Keith C Norris
IMPORTANCE: Religiosity has been associated with positive health outcomes. Hypothesized pathways for this association include religious practices, such as church attendance, that result in reduced stress. OBJECTIVE: The objective of this study was to examine the relationship between religiosity (church attendance), allostatic load (AL) (a physiologic measure of stress) and all-cause mortality in middle-aged adults. DESIGN, SETTING AND PARTICIPANTS: Data for this study are from NHANES III (1988-1994)...
2017: PloS One
https://www.readbyqxmd.com/read/28516298/modeled-traffic-noise-at-the-residence-and-colorectal-cancer-incidence-a-cohort-study
#10
Nina Roswall, Ole Raaschou-Nielsen, Matthias Ketzel, Kim Overvad, Jytte Halkjær, Mette Sørensen
PURPOSE: Traffic noise has become an increasing public health concern, associated with pervasive negative health effects, most likely through pathways of sleep disruption and stress. Both sleep disruption and stress have been associated with colorectal cancer. The purpose of this study was to investigate the association between residential traffic noise and colorectal cancer incidence. METHODS: Traffic noise was calculated for all residential addresses from 1987 to 2012 for 51,283 Danes in the Diet, Cancer and Health Cohort...
May 17, 2017: Cancer Causes & Control: CCC
https://www.readbyqxmd.com/read/28515316/dna-damage-induced-degradation-of-exo1-limits-dna-end-resection-to-ensure-accurate-dna-repair
#11
Nozomi Tomimatsu, Bipasha Mukherjee, Janelle Louise Harris, Francesca Ludovica Boffo, Molly Hardebeck, Patrick Ryan Potts, Kum Kum Khanna, Sandeep Burma
End resection of DNA double-strand breaks (DSBs) to generate 3'-single-stranded DNA facilitates DSB repair via error-free homologous recombination (HR) while stymieing repair by the error-prone non-homologous end joining (NHEJ) pathway. Activation of DNA end resection involves phosphorylation of the 5' to 3' exonuclease EXO1 by the phosphoinositide 3-kinase-like kinases ATM and ATR, and by the cyclin-dependent kinases 1 and 2. After activation, EXO1 must also be restrained in order to prevent over-resection which is known to hamper optimal HR and trigger global genomic instability...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28515175/role-for-reactive-oxygen-species-in-flow-stimulated-inner-medullary-collecting-duct-endothelin-1-production
#12
Will Wheatley, Donald E Kohan
Inner medullary collecting duct (IMCD)-derived endothelin-1 (ET-1) is stimulated by volume expansion, in part through augmented luminal flow, whereupon it can elicit natriuresis and diuresis. Since flow can alter nitric oxide (NO) and reactive oxygen species (ROS), both of which can affect collecting duct salt transport, we asked whether NO and/or ROS mediate flow-stimulated IMCD ET-1. Mouse IMCD3 cells were exposed to flow and ET-1/GAPDH mRNA assessed. A shear stress of 10 dyne/cm2 for 1 hr increased ET-1 mRNA by 4-fold compared to no flow (ET-1 flow response)...
May 17, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28513830/association-between-mutations-of-critical-pathway-genes-and-survival-outcomes-according-to-the-tumor-location-in-colorectal-cancer
#13
Dae-Won Lee, Sae-Won Han, Yongjun Cha, Jeong Mo Bae, Hwang-Phill Kim, Jaemyun Lyu, Hyojun Han, Hyoki Kim, Hoon Jang, Duhee Bang, Iksoo Huh, Taesung Park, Jae-Kyung Won, Seung-Yong Jeong, Kyu Joo Park, Gyeong Hoon Kang, Tae-You Kim
BACKGROUND: Colorectal cancer (CRC) develops through the alteration of several critical pathways. This study was aimed at evaluating the influence of critical pathways on survival outcomes for patients with CRC. METHODS: Targeted next-generation sequencing of 40 genes included in the 5 critical pathways of CRC (WNT, P53, RTK-RAS, phosphatidylinositol-4,5-bisphosphate 3-kinase [PI3K], and transforming growth factor β [TGF-β]) was performed for 516 patients with stage III or high-risk stage II CRC treated with surgery followed by adjuvant fluoropyrimidine and oxaliplatin chemotherapy...
May 17, 2017: Cancer
https://www.readbyqxmd.com/read/28504856/cell-free-dna-copy-number-variations-in-plasma-from-colorectal-cancer-patients
#14
Jian Li, Rachel L Dittmar, Shu Xia, Huijuan Zhang, Meijun Du, Chiang-Ching Huang, Brooke R Druliner, Lisa Boardman, Liang Wang
To evaluate clinical utility of cell free DNA (cfDNA), we performed whole genome sequencing to systematically examine plasma cfDNA copy number variations (CNVs) in a cohort of patients with colorectal cancer (CRC, n=80), polyps (n=20) and healthy controls (n=35). We initiallycompared cfDNA yield in 20 paired serum-plasma samples and observed significantly higher cfDNA concentration in serum (median=81.20ng, range 7.18-500ng/ml) than in plasma (median=5.09ng, range 3.76-62.8ng/ml) (p<0.0001). However, tumor-derived cfDNA content was significantly lower in serum than in matched plasma samples tested...
May 15, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28504812/overexpression-of-the-yap1-oncogene-in-clear-cell-renal-cell-carcinoma-is-associated-with-poor-outcome
#15
Agnieszka Rybarczyk, Jakub Klacz, Agata Wronska, Marcin Matuszewski, Zbigniew Kmiec, Piotr M Wierzbicki
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC (70-80%). Yes-associated protein 1 (YAP1) protein is a nuclear effector of the Hippo pathway and acts as a transcriptional co-activator of genes involved in the processes of growth and development of tissues. Hippo signaling, with its key kinases, MST2 and large tumor suppressor kinase 1 (LATS1), plays a significant role in the negative regulation of the amount and activity of YAP1 protein. Components of the Hippo pathway and YAP1 levels are frequently dysregulated in a variety of tumors, suggestive of their possible involvement in carcinogenesis...
May 15, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28502721/met-exon-14-skipping-mutations-in-lung-adenocarcinoma-clinicopathologic-implications-and-prognostic-values
#16
Geun Dong Lee, Seung Eun Lee, Doo-Yi Oh, Dan-Bi Yu, Hae Min Jeong, Jooseok Kim, Sungyoul Hong, Hun Soon Jung, Ensel Oh, Ji-Young Song, Mi-Sook Lee, Mingi Kim, Kyungsoo Jung, Jhingook Kim, Young Kee Shin, Yoon-La Choi, Hyeong Ryul Kim
INTRODUCTION: Response to MET inhibitors in non-small cell lung cancer with MET exon 14 (METex14) skipping has fueled molecular screening efforts and search for optimal therapies. However, further work is needed to refine the clinicopathologic and prognostic implications of METex14 skipping METHODS: Among 795 East-Asian patients who underwent surgery for non-small cell lung cancer, we screened 45 patients with quintuple-negative (EGFR-/KRAS-/ALK-/ROS1-/RET-) lung adenocarcinomas using RT-PCR, and found 17 patients (37...
May 10, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28496006/gene-expression-signature-of-gleason-score-is-associated-with-prostate-cancer-outcomes-in-a-radical-prostatectomy-cohort
#17
Min A Jhun, Milan S Geybels, Jonathan L Wright, Suzanne Kolb, Craig April, Marina Bibikova, Elaine A Ostrander, Jian-Bing Fan, Ziding Feng, Janet L Stanford
Prostate cancer (PCa) is a leading cause of cancer-related mortality worldwide. Gleason score (GS) is one of the best predictors of PCa aggressiveness, but additional tumor biomarkers may improve its prognostic accuracy. We developed a gene expression signature of GS to enhance the prediction of PCa outcomes. Elastic net was used to construct a gene expression signature by contrasting GS 8-10 vs. ≤6 tumors in The Cancer Genome Atlas (TCGA) dataset. The constructed signature was then evaluated for its ability to predict recurrence and metastatic-lethal (ML) progression in a Fred Hutchinson (FH) patient cohort (N=408; NRecurrence=109; NMLprogression=27)...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28490533/the-tryptophan-kynurenine-pathway-systemic-inflammation-and-long-term-outcome-after-kidney-transplantation
#18
Laura V de Vries, Isidor Minovic, Casper Fm Franssen, Martijn van Faassen, Jan-Stephan F Sanders, Stefan P Berger, Gerjan Navis, Ido P Kema, Stephan Jl Bakker
BACKGROUND: Tryptophan is metabolized along the kynurenine pathway, initially to kynurenine, and subsequently to cytotoxic 3-hydroxykynurenine. There is increasing interest in this pathway, because of its pro-inflammatory nature, and drugs interfering in it receive increasing attention. We aimed to investigate whether serum and urinary parameters of the tryptophan-kynurenine pathway, and particularly cytotoxic 3-hydroxykynurenine, are associated with systemic inflammation and long-term outcome in renal transplant recipients (RTR)...
May 10, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28489907/anti-oxidative-effects-of-4-hydroxybenzyl-alcohol-in-astrocytes-confer-protective-effects-in-autocrine-and-paracrine-manners
#19
Lidan Luo, Seung-Woo Kim, Hye-Kyung Lee, Il-Doo Kim, Hahnbie Lee, Ja-Kyeong Lee
4-Hydroxybenzyl alcohol (4-HBA) is an important phenolic constituent of Gastrodia elata Blume (GEB), a traditional herbal medicine used in East Asia. Many activities have been reported to underlie the beneficial effects of 4-HBA in the brain, and in particular, its anti-inflammatory, anti-oxidative, and anti-zinc-toxic effects have been implicated in the postischemic brain. Here, the authors investigated the anti-oxidative effect of 4-HBA on astrocytes and sought to identify the underlying molecular mechanisms involved...
2017: PloS One
https://www.readbyqxmd.com/read/28489509/akt-inhibition-in-solid-tumors-with-akt1-mutations
#20
David M Hyman, Lillian M Smyth, Mark T A Donoghue, Shannon N Westin, Philippe L Bedard, Emma J Dean, Hideaki Bando, Anthony B El-Khoueiry, José A Pérez-Fidalgo, Alain Mita, Jan H M Schellens, Matthew T Chang, Jonathan B Reichel, Nancy Bouvier, S Duygu Selcuklu, Tara E Soumerai, Jean Torrisi, Joseph P Erinjeri, Helen Ambrose, J Carl Barrett, Brian Dougherty, Andrew Foxley, Justin P O Lindemann, Robert McEwen, Martin Pass, Gaia Schiavon, Michael F Berger, Sarat Chandarlapaty, David B Solit, Udai Banerji, José Baselga, Barry S Taylor
Purpose AKT1 E17K mutations are oncogenic and occur in many cancers at a low prevalence. We performed a multihistology basket study of AZD5363, an ATP-competitive pan-AKT kinase inhibitor, to determine the preliminary activity of AKT inhibition in AKT-mutant cancers. Patients and Methods Fifty-eight patients with advanced solid tumors were treated. The primary end point was safety; secondary end points were progression-free survival (PFS) and response according to Response Evaluation Criteria in Solid Tumors (RECIST)...
May 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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