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https://www.readbyqxmd.com/read/29332294/detection-of-mapk3-6-phosphorylation-during-hypersensitive-response-hr-associated-programmed-cell-death-in-plants
#1
Qingyu Wu, David Jackson
Programmed cell death (PCD) is an essential component of development, biotic and abiotic responses. Hypersensitive response (HR)-associated cell death activated under pathogen attack is one of the most dramatic manifestations of PCD in plants. Signal transduction through mitogen-activated protein kinase (MAPK) cascades, a very conserved signaling pathway across eukaryotes, is a core mediator for HR-associated PCD. Therefore, monitoring MAPK activation enables the mechanisms underlying HR-associated PCD to be elucidated...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29331750/phosphoinositide-3-kinase-inhibitors-in-advanced-breast-cancer-a-systematic-review-and-meta-analysis
#2
REVIEW
Jacques Raphael, Danielle Desautels, Kathleen I Pritchard, Ekaterina Petkova, Prakeshkumar S Shah
Phosphoinositide 3-kinase (PI3K) inhibitors may overcome drug resistance and improve advanced breast cancer (ABC) outcomes. We conducted a systematic review and meta-analysis to assess the efficacy and safety of adding a PI3K inhibitor to the standard of care (SOC) treatment in ABC. The electronic databases Ovid, PubMed, Cochrane Central Register of Controlled Trials and Embase, were searched for relevant randomised trials. Pooled hazard ratios (HRs) for progression-free survival (PFS) and pooled risk ratios (RRs) for objective response rates (ORRs), disease control rates (DCRs) and toxicity were meta-analysed using the Mantel-Haenszel method and generic inverse variance...
January 10, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29331073/cerebrospinal-fluid-macrophage-biomarkers-in-amyotrophic-lateral-sclerosis
#3
A G Thompson, E Gray, M-L Thézénas, P D Charles, S Evetts, M T Hu, K Talbot, R Fischer, B M Kessler, M R Turner
Objective The neurodegenerative disease amyotrophic lateral sclerosis (ALS) is a heterogeneous clinical syndrome involving multiple molecular pathways. The development of biomarkers for use in therapeutic trials is a priority. We sought to use a high-throughput proteomic method to identify novel biomarkers in individual cerebrospinal fluid samples. Methods Liquid chromatography-tandem mass spectrometry with label-free quantification was used to identify cerebrospinal fluid proteins using samples from a well-characterised longitudinal cohort comprising patients with ALS (n=43), the upper motor neuron variant primary lateral sclerosis (PLS, n=6), cross-sectional healthy (n=20) and disease controls (Parkinsons's n=20, ALS mimic disorders n=12)...
January 13, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29323287/disposition-of-a-glucose-load-into-hepatic-glycogen-by-direct-and-indirect-pathways-in-juvenile-seabass-and-seabream
#4
João Rito, Ivan Viegas, Miguel A Pardal, Isidoro Metón, Isabel V Baanante, John G Jones
In carnivorous fish, conversion of a glucose load to hepatic glycogen is widely used to assess their metabolic flexibility towards carbohydrate utilization, but the activities of direct and indirect pathways in this setting are unclear. We assessed the conversion of an intraperitoneal glucose load (2 g.kg-1) enriched with [U-13C6]glucose to hepatic glycogen in juvenile seabass and seabream. 13C-NMR analysis of glycogen was used to determine the contribution of the load to glycogen synthesis via direct and indirect pathways at 48-hr post-injection...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29320557/high-ahr-expression-in-breast-tumors-correlates-with-expression-of-genes-from-several-signaling-pathways-namely-inflammation-and-endogenous-tryptophan-metabolism
#5
Sophie Vacher, Patrice Castagnet, Walid Chemlali, François Lallemand, Didier Meseure, Marc Pocard, Ivan Bieche, Martine Perrot-Applanat
Increasing epidemiological and animal experimental data provide substantial support for the role of aryl hydrocarbon receptor (AhR) in mammary tumorigenesis. The effects of AhR have been clearly demonstrated in rodent models of breast carcinogenesis and in several established human breast cancer cell lines following exposure to AhR ligands or AhR overexpression. However, relatively little is known about the role of AhR in human breast cancers. AhR has always been considered to be a regulator of toxic and carcinogenic responses to environmental contaminants such as TCDD (dioxin) and benzo[a]pyrene (BaP)...
2018: PloS One
https://www.readbyqxmd.com/read/29316844/pi3k-pathway-and-bcl-2-family-clinicopathological-features-in-prostate-cancer
#6
Norelia Torrealba, Gonzalo Rodriguez-Berriguete, Benito Fraile, Gabriel Olmedilla, Pilar Martínez-Onsurbe, Manuel Sánchez-Chapado, Ricardo Paniagua, Mar Royuela
The phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathways and Bcl-2 family play a central role in prostate cancer (PC). The aim was to determine influence in the biochemical progression in PC. To evaluate the association between clinic pathological and immunohistochemical variables, Spearman's test was performed. Log-rank test and Kaplan-Meier curves were used for survival comparisons. To explore the correlation of the studied immunohistochemical parameters and the established prognostic variables with biochemical progression, univariate and multivariate Cox proportional Hazard regression analyses were performed...
January 9, 2018: Aging Male: the Official Journal of the International Society for the Study of the Aging Male
https://www.readbyqxmd.com/read/29315367/sudden-death-in-patients-with-ebstein-anomaly
#7
Christine H Attenhofer Jost, Nicholas Y Tan, Abdalla Hassan, Emily R Vargas, David O Hodge, Joseph A Dearani, Heidi Connolly, Samuel J Asirvatham, Christopher J McLeod
Aims: Ventricular dysfunction or structural alteration of either ventricle is a well-established risk factor for sudden death (SD). Ebstein anomaly (EA) can present with both right and left heart abnormalities; however, predictors of SD have not been described. We therefore sought to characterize the incidence and risk factors of SD among a large cohort of patients with EA. Methods and results: All EA patients who underwent evaluation at a high-volume institution over a 4-decade period were retrospectively reviewed...
January 5, 2018: European Heart Journal
https://www.readbyqxmd.com/read/29313974/genetic-variants-in-rora-and-dnmt1-associated-with-cutaneous-melanoma-survival
#8
Bo Li, Yanru Wang, Yinghui Xu, Hongliang Liu, Wendy Bloomer, Dakai Zhu, Christopher I Amos, Shenying Fang, Jeffrey E Lee, Xin Li, Jiali Han, Qingyi Wei
Cutaneous melanoma (CM) is considered as a steroid hormone-related malignancy. However, few studies have evaluated the roles of genetic variants encoding steroid hormone receptor genes and their related regulators (SHR-related genes) in CM-specific survival (CMSS). Here, we performed a pathway-based analysis to evaluate genetic variants of 191 SHR-related genes in 858 CMSS patients using a dataset from a genome-wide association study (GWAS) from The University of Texas MD Anderson Cancer Center (MDACC), and then validated the results in an additional dataset of 409 patients from the Harvard GWAS...
January 4, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29313814/biomarker-integrated-neoadjuvant-dasatinib-trial-in-resectable-malignant-pleural-mesothelioma
#9
Anne S Tsao, Heather Lin, Brett W Carter, J Jack Lee, David Rice, Ara Vaporcyan, Steven Swisher, Reza Mehran, John Heymach, Monique Nilsson, Youhong Fan, Maria Nunez, Lixia Diao, Jing Wang, Junya Fujimoto, Ignacio I Wistuba, Waun Ki Hong
Window-of-opportunity trials in malignant pleural mesothelioma (MPM) are challenging but can yield important translational information about a novel agent. We treated MPM patients (n=24) with 4 weeks of oral dasatinib followed by surgery with or without radiotherapy and then an optional 2 years of maintenance dasatinib. The primary endpoint was biomarker modulation of p-SrcTyr419. For all patients, the median PFS was 7.5 months and OS 19.1 months. No significant responses were seen after 4 weeks of dasatinib therapy, however, modulation of p-SrcTyr419 immunohistochemistry (IHC) scores (median (interquartile range) = 70 (37...
December 4, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29307087/targeting-the-prostacyclin-pathway-with-selexipag-in-patients-with-pulmonary-arterial-hypertension-receiving-double-combination-therapy-insights-from-the-randomized-controlled-griphon-study
#10
J Gerry Coghlan, Richard Channick, Kelly Chin, Lilla Di Scala, Nazzareno Galiè, Hossein-Ardeschir Ghofrani, Marius M Hoeper, Irene M Lang, Vallerie McLaughlin, Ralph Preiss, Lewis J Rubin, Gérald Simonneau, Olivier Sitbon, Victor F Tapson, Sean Gaine
BACKGROUND: In pulmonary arterial hypertension (PAH), combination therapy is an important treatment strategy. Although randomized controlled trial data are available to support the combination of two therapies, data regarding triple combination therapy are few. OBJECTIVE: The phase III GRIPHON trial enrolled 1156 patients with PAH, including 376 receiving background double combination therapy. We evaluated the efficacy and safety of selexipag as a third agent in these patients and further analyzed this subgroup according to symptom burden at baseline as indicated by World Health Organization (WHO) functional class (FC)...
January 6, 2018: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
https://www.readbyqxmd.com/read/29306596/diabetes-mellitus-after-injury-in-burn-and-non-burned-patients-a-population-based-retrospective-cohort-study
#11
Janine M Duke, Sean M Randall, Mark W Fear, James H Boyd, Suzanne Rea, Fiona M Wood
OBJECTIVE: To compare hospitalisations for diabetes mellitus (DM) after injury experienced by burn patients, non-burn trauma patients and people with no record of injury admission, adjusting for socio-demographic, health and injury factors. METHODS: Linked hospital and death data for a burn patient cohort (n=30,997) in Western Australia during the period 1980-2012 and two age and gender frequency matched comparison cohorts: non-burn trauma patients (n=28,647); non-injured people (n=123,399)...
January 3, 2018: Burns: Journal of the International Society for Burn Injuries
https://www.readbyqxmd.com/read/29299828/fibroblast-growth-factor-receptor-1-and-3-expression-is-associated-with-regulatory-pi3k-akt-kinase-activity-as-well-as-invasion-and-prognosis-in-human-laryngeal-cancer
#12
Katarzyna Starska, Ewa Forma, Iwona Lewy-Trenda, Olga Stasikowska-Kanicka, Michał Skóra, Magdalena Bryś
PURPOSE: Aberrant fibroblast growth factor receptor (FGFR) expression is thought to contribute to the development of many types of cancer. As yet, however, their impact on the course and prognosis of head and neck cancer remains to be determined. Here, we aimed to investigate the effects of expression of the FGFR family members FGFR1 and FGFR3, as well as their downstream PI3K/AKT signal-regulated kinases, on the aggressiveness and prognosis of laryngeal cancer. METHODS: In total 137 surgically removed squamous cell laryngeal cancer (SCLC) and 100 matched non-cancerous laryngeal mucosa (NCLM) samples were assessed for mRNA expression using quantitative real-time PCR...
January 3, 2018: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/29298992/germline-variants-in-il4-mgmt-and-akt1-are-associated-with-prostate-cancer-specific-mortality-an-analysis-of-12-082-prostate-cancer-cases
#13
L M FitzGerald, S Zhao, A Leonardson, M S Geybels, S Kolb, D W Lin, J L Wright, R Eeles, Z Kote-Jarai, K Govindasami, G G Giles, M C Southey, J Schleutker, T L Tammela, C Sipeky, K L Penney, M J Stampfer, H Gronberg, F Wiklund, P Stattin, J Hugosson, D M Karyadi, E A Ostrander, Z Feng, J L Stanford
BACKGROUND: Prostate cancer (PCa) is a leading cause of mortality and genetic factors can influence tumour aggressiveness. Several germline variants have been associated with PCa-specific mortality (PCSM), but further replication evidence is needed. METHODS: Twenty-two previously identified PCSM-associated genetic variants were genotyped in seven PCa cohorts (12,082 patients; 1544 PCa deaths). For each cohort, Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for risk of PCSM associated with each variant...
January 3, 2018: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/29296784/high-proportions-of-pd-1-and-pd-l1-leukocytes-in-classical-hodgkin-lymphoma-microenvironment-are-associated-with-inferior-outcome
#14
Peter Hollander, Peter Kamper, Karin Ekstrom Smedby, Gunilla Enblad, Maja Ludvigsen, Julie Mortensen, Rose-Marie Amini, Stephen Hamilton-Dutoit, Francesco d'Amore, Daniel Molin, Ingrid Glimelius
Immune checkpoint inhibition targeting the programmed death receptor (PD)-1 pathway is a novel treatment approach in relapsed and refractory classical Hodgkin lymphoma (cHL). Identifying patients with a high risk of treatment failure could support the use of PD-1 inhibitors as front-line treatment. Our aim was to investigate the prognostic impact of PD-1, programmed death-ligand 1 (PD-L1), and PD-L2 in the tumor microenvironment in diagnostic biopsies of patients with cHL. Patients from Denmark and Sweden, diagnosed between 1990 and 2007 and ages 15 to 86 years, were included...
August 8, 2017: Blood Advances
https://www.readbyqxmd.com/read/29291002/mutations-in-the-dna-methylation-pathway-and-number-of-driver-mutations-predict-response-to-azacitidine-in-myelodysplastic-syndromes
#15
M Teresa Cedena, Inmaculada Rapado, Alejandro Santos-Lozano, Rosa Ayala, Esther Onecha, María Abaigar, Esperanza Such, Fernando Ramos, José Cervera, María Díez-Campelo, Guillermo Sanz, Jesús Hernández Rivas, Alejandro Lucía, Joaquin Martínez-López
We evaluated the association of mutations in 34 candidate genes and response to azacitidine in 84 patients with myelodysplastic syndrome (MDS), with 217 somatic mutations identified by next-generation sequencing. Most patients (93%) had ≥1 mutation (mean=2.6/patient). The overall response rate to azacitidine was 42%. No clinical characteristic was associated with response to azacitidine. However, total number of mutations/patient was negatively associated with overall drug response (odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29289609/regulatory-variants-in-cancer-related-pathway-genes-predict-survival-of-patients-with-surgically-resected-non-small-cell-lung-cancer
#16
Kyung Min Shin, Mi Jeong Hong, Shin Yup Lee, Cheng Cheng Jin, Sun Ah Baek, Jang Hyuck Lee, Jin Eun Choi, Hyo-Gyoung Kang, Won Kee Lee, Yangki Seok, Eung Bae Lee, Ji Yun Jeong, Seung Soo Yoo, Jaehee Lee, Seung Ick Cha, Chang Ho Kim, Young Chul Kim, In Jae Oh, Kook Joo Na, Sukki Cho, Sanghoon Jheon, Jae Yong Park
BACKGROUND: We conducted this study to identify genetic variants in cancer-related pathway genes which can predict prognosis of NSCLC patients after surgery, using a comprehensive list of regulatory single nucleotide polymorphisms (SNPs) prioritized by RegulomeDB. METHOD: A total of 509 potentially functional SNPs in cancer-related pathway genes selected from RegulomeDB were evaluated. These SNPs were analyzed in a discovery set (n=354), and a replication study was performed in an independent set (n=772)...
December 28, 2017: Gene
https://www.readbyqxmd.com/read/29285225/the-protective-value-of-mir-204-5p-for-prognosis-and-its-potential-gene-network-in-various-malignancies-a-comprehensive-exploration-based-on-rna-seq-high-throughput-data-and-bioinformatics
#17
Zhi-Hua Ye, Dong-Yue Wen, Xiao-Yong Cai, Liang Liang, Pei-Rong Wu, Hui Qin, Hong Yang, Yun He, Gang Chen
Purpose: The prognostic role of miR-204-5p (previous ID: miR-204) is varied and inconclusive in diverse types of malignant neoplasm. Therefore, the purposes of the study comprehensively explore the overall prognostic role of miR-204-5p based on high-throughput microRNA sequencing data, and to investigate the potential role of miR-204-5p via bioinformatics approaches. Materials and Methods: The data of microRNA sequencing and survival were downloaded from The Cancer Genome Atlas (TCGA), and the prognostic value of miR-204-5p was analyzed by using Kaplan-Meier and univariate cox regressions...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29280853/longitudinal-associations-of-neighborhood-level-racial-residential-segregation-with-obesity-among-blacks
#18
Lindsay R Pool, Mercedes R Carnethon, David C Goff, Penny Gordon-Larsen, Whitney R Robinson, Kiarri N Kershaw
BACKGROUND: Despite nearly 50 years since the passage of the Fair Housing Act of 1968, the majority of black Americans continue to live in highly segregated communities. Differing exposure to obesogenic environments in segregated neighborhoods may contribute to racial disparities in obesity prevalence. METHODS: We used prospective data from the Coronary Artery Risk Development in Young Adults (CARDIA) study to examine associations between levels of neighborhood-level racial residential segregation and incident obesity in black men and women...
December 26, 2017: Epidemiology
https://www.readbyqxmd.com/read/29277410/hiv-related-stigma-racial-discrimination-and-gender-discrimination-pathways-to-physical-and-mental-health-related-quality-of-life-among-a-national-cohort-of-women-living-with-hiv
#19
Carmen H Logie, Ying Wang, Ashley Lacombe-Duncan, Anne C Wagner, Angela Kaida, Tracey Conway, Kath Webster, Alexandra de Pokomandy, Mona R Loutfy
Social inequities compromise health-related quality of life (HR-QoL) among women living with HIV (WLWH). Little is known about health impacts of intersecting stigma based on HIV status, race and gender among WLWH or potential mechanisms to promote HR-QoL. We tested pathways from multiple types of stigma (HIV-related, racial, gender) to physical and mental HR-QoL utilizing baseline survey data from a national cohort of WLWH in Canada (2013-2015). Structural equation modeling was conducted using maximum likelihood estimation methods to test the direct effects of HIV-related stigma, racial discrimination and gender discrimination on HR-QoL and indirect effects via social support and economic insecurity, adjusting for socio-demographic factors...
December 22, 2017: Preventive Medicine
https://www.readbyqxmd.com/read/29275435/homologous-recombination-deficiency-hrd-status-predicts-response-to-standard-neoadjuvant-chemotherapy-in-patients-with-triple-negative-or-brca1-2-mutation-associated-breast-cancer
#20
Melinda L Telli, Jessica Hellyer, William Audeh, Kristin C Jensen, Shikha Bose, Kirsten M Timms, Alexander Gutin, Victor Abkevich, Rebecca N Peterson, Chris Neff, Elisha Hughes, Zaina Sangale, Joshua Jones, Anne-Renee Hartman, Pei-Jen Chang, Shaveta Vinayak, Richard Wenstrup, James M Ford
PURPOSE: Defects in the homologous recombination (HR) DNA repair pathway sensitize tumors to therapeutics that target this pathway. A significant proportion of triple-negative breast cancers (TNBC) carry HR defects. The HRD assay is highly associated with sensitivity to neoadjuvant platinum-based chemotherapy in TNBC. Standard chemotherapy consists of some combination of an anthracycline, cyclophosphamide, and taxane. This study assesses the association of HR deficiency status with response to standard neoadjuvant chemotherapy in TNBC or BRCA1/2 mutation-associated breast cancer...
December 23, 2017: Breast Cancer Research and Treatment
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