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https://www.readbyqxmd.com/read/28646291/application-of-open-access-databases-to-determine-functional-connectivity-between-resveratrol-binding-protein-qr2-and-colorectal-carcinoma
#1
Barbara B Doonan, Evelien Schaafsma, John T Pinto, Joseph M Wu, Tze-Chen Hsieh
Colorectal cancer (CRC) is a major cause of cancer-associated deaths worldwide. Recently, oral administration of resveratrol (trans-3,5,4'-trihydroxystilbene) has been reported to significantly reduce tumor proliferation in colorectal cancer patients, however, with little specific information on functional connections. The pathogenesis and development of colorectal cancer is a multistep process that can be categorized using three phenotypic pathways, respectively, chromosome instability (CIN), microsatellite instability (MSI), and CpG island methylator (CIMP)...
June 23, 2017: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/28645942/mutational-heterogeneity-in-apc-and-kras-arises-at-the-crypt-level-and%C3%A2-leads-to-polyclonality-in-early-colorectal-tumorigenesis
#2
Mireia Gausachs, Ester Borras, Kyle Chang, Sara González, Daniel Azuara, Axel Delgado Amador, Adriana Lopez-Doriga, F Anthony San Lucas, Xavier Sanjuan, Maria jOSE Paules, Melissa Taggart, Gareth Davies, Erik A Ehli, Jerry Fowler, Victor Moreno, Marta Pineda, Y Nancy You, Patrick M Lynch, Conxi Lazaro, Nicholas E Navin, Paul Scheet, Ernest T Hawk, Gabriel Capella, Eduardo Vilar
Purpose:  The majority of genomic alterations causing intratumoral heterogeneity (ITH) in colorectal cancer (CRC) are thought to arise during early stages of carcinogenesis as a burst but only after truncal mutations in APC have expanded a single founder clone. We have investigated if the initial source of ITH is consequent to multiple independent lineages derived from different crypts harboring distinct truncal APC and driver KRAS mutations, thus challenging the prevailing monoclonal monocryptal model. <p>Experimental design: High-depth next-generation sequencing and SNP arrays were performed in whole lesion extracts of 37 FAP colorectal adenomas...
June 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28645718/optimizing-adjuvants-for-intradermal-delivery-of-menc-glycoconjugate-vaccine
#3
Agnese Donadei, Cristiana Balocchi, Maria R Romano, Luigi Panza, Roberto Adamo, Francesco Berti, Derek T O'Hagan, Simona Gallorini, Barbara C Baudner
Intradermal vaccine delivery is a promising alternative to the conventional intramuscular route. The skin layer is immunologically supported by a densely network of antigen presenting cells, while the skeletal muscle is loaded with a relatively sparse population of APCs. Nevertheless, the vaccine to be suitable for intradermal delivery needs a new formulation to facilitate either smaller injection volumes or the introduction into new delivery devises as micro-needles. This study presents a proof of concept for intradermal delivery of the MenC-CRM197 glycoconjugate vaccine using a mouse model...
June 20, 2017: Vaccine
https://www.readbyqxmd.com/read/28644724/modeling-long-term-effects-attributed-to-nitrogen-dioxide-no2-and-sulfur-dioxide-so2-exposure-on-asthma-morbidity-in-a-nationwide-cohort-in-israel
#4
N Greenberg, R S Carel, E Derazne, A Tiktinsky, D Tzur, B A Portnov
Studies have provided extensive documentation that acutely elevated environmental exposures contribute to chronic health problems. However, only attention has been paid to the effects of modificate of exposure assessment methods in environmental health investigations, leading to uncertainty and gaps in our understanding of exposure- and dose-response relationships. The goal of the present study was to evaluate whether average or peak concentration exerts a greater influence on asthma outcome, and which of the exposure models may better explain various physiological responses generated by nitrogen dioxide (NO2) or sulfur dioxide (SO2) air pollutants...
June 23, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28642551/aesthetic-preformed-crowns-for-primary-teeth
#5
Greig D Taylor
Data sourcesMedline, Cochrane central register of controlled trials, US National Institutes of Health Trials Register and the World Health Organization International Clinical Trials Registry Platform.Study selectionEnglish language randomised clinical trials comparing APCs with conventional restorative techniques for primary teeth.Data extraction and synthesisStudy selection and data abstraction were conducted independently by two reviewers. Risk of bias was assessed using the Cochrane risk of bias tool. Study characteristics and results were described qualitatively...
June 23, 2017: Evidence-based Dentistry
https://www.readbyqxmd.com/read/28642280/granulocytes-as-modulators-of-dendritic-cell-function
#6
REVIEW
Annelot Breedveld, Tom Groot Kormelink, Marjolein van Egmond, Esther de Jong
Effector T cell development is directly driven by APCs, in particular, by antigen-primed dendritic cells (DCs). Depending on the pathogenic stimulus and the microenvironment, DCs induce proliferation and polarization of naive CD4(+) T cells into different effector subsets, such as Th1, Th2, Th17, or regulatory T cells (Tregs). During inflammation, DCs are found in close proximity to other innate immune cells, including all granulocyte subtypes, which potentially influence the immunomodulatory capacities of DCs...
June 22, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28641072/overweight-obesity-and-extreme-obesity-among-mississippi-adults-2001-2010-and-2011-2015
#7
Vincent L Mendy, Rodolfo Vargas, Gerri Cannon-Smith, Marinelle Payton
INTRODUCTION: In 2015, about 1.5 million adults in Mississippi were overweight or obese. Obesity is associated with increased risk for diabetes and cardiovascular problems. We examined trends in the prevalence of overweight, obesity, and extreme obesity from 2001 through 2010 and 2011 through 2015. METHODS: We used data from the Mississippi Behavioral Risk Factor Surveillance System to analyze trends in the prevalence of overweight, obesity, and extreme obesity among adults from 2001 through 2010 and 2011 through 2015...
June 22, 2017: Preventing Chronic Disease
https://www.readbyqxmd.com/read/28637901/caveolin-1-influences-lfa-1-redistribution-upon-tcr-stimulation-in-cd8-t-cells
#8
Jessica G Borger, Vicky L Morrison, Andrew Filby, Celine Garcia, Liisa M Uotila, Fabio Simbari, Susanna C Fagerholm, Rose Zamoyska
TCR stimulation by peptide-MHC complexes on APCs requires precise reorganization of molecules into the area of cellular contact to form an immunological synapse from where T cell signaling is initiated. Caveolin (Cav)1, a widely expressed transmembrane protein, is involved in the regulation of membrane composition, cellular polarity and trafficking, and the organization of signal transduction pathways. The presence of Cav1 protein in T cells was identified only recently, and its function in this context is not well understood...
June 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28637009/jagged-2-jag2-enhances-tumorigenicity-and-chemoresistance-of-colorectal-cancer-cells
#9
Vivek Vaish, Joohwee Kim, Minsub Shim
Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality. Recent studies have stated that NOTCH signaling plays an important role in the development and progression of CRC. However, the role of Jagged-2 (JAG2), one of the NOTCH ligands, has not been delineated in colorectal tumorigenesis and drug resistance. In the present study, we have examined the impact of targeting JAG2 on CRC cells. Among all the members of NOTCH ligands, only the expression of JAG2 was found up-regulated in the intestinal tumors of ApcMin/+ mice as compared to the nearby normal mucosa...
June 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636782/changing-trends-in-complications-of-chronic-hepatitis-c
#10
Mei Lu, Jia Li, Loralee B Rupp, Yueren Zhou, Scott D Holmberg, Anne C Moorman, Philip R Spradling, Eyasu H Teshale, Joseph A Boscarino, Yihe G Daida, Mark A Schmidt, Sheri Trudeau, Stuart C Gordon
BACKGROUND AND AIMS: Chronic hepatitis C virus (HCV)-related complications have increased over the past decade. METHODS: We used join-point regression modeling to investigate trends in these complications from 2006-2015, and the impact of demographics on these trends. Using data from the Chronic Hepatitis Cohort Study (CHeCS), we identified points at which the trend significantly changed, and estimated the annual percent change (APC) in rates of cirrhosis, decompensated cirrhosis, and all-cause mortality, adjusted by race, sex, and age...
June 21, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28635239/-an-analysis-of-incidence-trends-and-characteristics-of-soft-tissue-sarcoma-in-beijing-1999-2013
#11
L Yang, Z W Fang, Z F Fan, N Wang, Y N Yuan, H C Li, S Liu
Objective: To analyze the incidence trends and to describe the characteristics of soft tissue sarcoma (STS) among residents in Beijing from 1999 to 2013. Methods: Medical information of the cases diagnosed as STS(ICD10: C47&C49) from 1999 to 2013 in Beijing was extracted from the population-based database of Beijing Cancer Registry.Crude incidence rate, age-standardized incidence rates to Chinese population (ASRC)and the world population(ASRW) were calculated. The characteristics of the STS cases in different gender and age groups from urban and rural areas were respectively analyzed...
June 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28634351/a-dynamical-model-for-activating-and-silencing-the-mitotic-checkpoint
#12
Richard Henze, Peter Dittrich, Bashar Ibrahim
The spindle assembly checkpoint (SAC) is an evolutionarily conserved mechanism, exclusively sensitive to the states of kinetochores attached to microtubules. During metaphase, the anaphase-promoting complex/cyclosome (APC/C) is inhibited by the SAC but it rapidly switches to its active form following proper attachment of the final spindle. It had been thought that APC/C activity is an all-or-nothing response, but recent findings have demonstrated that it switches steadily. In this study, we develop a detailed mathematical model that considers all 92 human kinetochores and all major proteins involved in SAC activation and silencing...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634215/vaccination-with-high-affinity-epitopes-impairs-antitumor-efficacy-by-increasing-pd-1expression-on-cd8-t-cells
#13
Christopher D Zahm, Viswa Colluru, Douglas G McNeel
Antitumor vaccines encoding self-antigens generally have low immunogenicity in clinical trials. Several approaches are aimed at improving vaccine immunogenicity, including efforts to alter encoded epitopes. Immunization with epitopes altered for increased affinity for the major histocompatibility complex (MHC) or T-cell receptor (TCR) elicits greater numbers of CD8 T cells but inferior antitumor responses. Our previous results suggested that programmed death 1 (PD-1) and its ligand (PD-L1) increased on antigen-specific CD8 T cells and tumor cells, respectively, after high-affinity vaccination...
June 20, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28633930/phospholipase-a2-in-the-venom-of-three-cottonmouth-snakes
#14
Ying Jia, Boris Ermolinsky, Aryana Garza, Daniele Provenzano
Two phospholipase A2s (PLA2s), Asp49 (D49) and Lys49 (K49), were purified by one-step reverse-phase high performance liquid chromatography (RP-HPLC) from the venom of each of the three subspecies of cottonmouth snake, Western cottonmouth (Agkistrodon piscivorus leucostoma; Apl), Eastern cottonmouth (Agkistrodon piscivorus piscivorus; App) and Florida cottonmouth (Agkistrodon piscivorus conanti; Apc). Venom protein profiles and PLA2s elution pattern of the three cottonmouth snakes were remarkably similar displaying four similar sharp and two wide peaks; in all cases K49 PLA2 eluted first followed by D49 PLA2...
June 17, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28632731/cd47-overexpression-is-associated-with-decreased-neutrophil-apoptosis-phagocytosis-and-poor-prognosis-in-non-small-cell-lung-cancer-patients
#15
Lourdes Barrera, Edgar Montes-Servín, Juan-Manuel Hernandez-Martinez, María de Los Ángeles García-Vicente, Elizabeth Montes-Servín, Marytere Herrera-Martínez, José C Crispín, José Rafael Borbolla-Escoboza, Oscar Arrieta
BACKGROUND: Non-small-cell lung cancer (NSCLC) patients often exhibit neutrophilia, which has been associated with poor clinical outcomes. However, the mechanisms that lead to neutrophilia have not been fully established. CD47 is an antiphagocytic molecule that promotes neutrophil recruitment. METHODS: Blood was collected from 50 treatment-naive patients with advanced NSCLC and from 25 healthy subjects. The frequency of CD66b(+) cells and the expression of CD47 were determined by flow cytometry...
June 20, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28632502/targeting-activated-protein-c-to-treat-hemophilia
#16
Stéphanie G I Polderdijk, Trevor P Baglin, James A Huntington
PURPOSE OF REVIEW: Hemophilia is a debilitating disease, marked by frequent, painful bleeding events, joint deterioration and early death. All current treatments consist of i.v. infusions of replacement factor or other procoagulant factors, and are incompletely effective, due in part to the short half-lives of the proteins. An alternative approach is to rebalance hemostasis by inhibiting natural anticoagulant mechanisms. In this article, we explain why activated protein C (APC) is an appropriate and safe target for the treatment of hemophilia...
June 16, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28630103/up-regulation-of-ep2-and-ep3-receptors-in-human-tolerogenic-dendritic-cells-boost-the-immunosuppressive-activity-of-pge2
#17
Georgina Flórez-Grau, Raquel Cabezón, Kyra J E Borgman, Carolina España, Juan Jose Lozano, Maria F Garcia-Parajo, Daniel Benítez-Ribas
Dendritic cells (DCs) are APCs essential in regulating the immune response. PGE2, produced during inflammation, has a pivotal role in the maturation of DCs and, therefore, is vital for the immune response. The large variety of biologic functions governed by PGE2 is mediated by its signaling through 4 distinct E-type prostanoid (EP) receptors. Immunogenic DCs express EP2 and EP4, which mediate the PGE2 signaling. However, the expression and function of EP receptors in human tolerogenic DCs (tol-DCs), which present an inhibitory phenotype, have not yet, to our knowledge, been assessed...
June 19, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28629331/depletion-of-p21-activated-kinase-1-up-regulates-the-immune-system-of-apc-%C3%A2-14-mice-and-inhibits-intestinal-tumorigenesis
#18
Nhi Huynh, Kai Wang, Mildred Yim, Chelsea J Dumesny, Mauro S Sandrin, Graham S Baldwin, Mehrdad Nikfarjam, Hong He
BACKGROUND: P21-activated kinase 1 (PAK1) stimulates growth and metastasis of colorectal cancer (CRC) through activation of multiple signalling pathways. Up-regulation of CRC stem cell markers by PAK1 also contributes to the resistance of CRC to 5-fluorouracil. The aim of this study was to investigate the effect of PAK1 depletion and inhibition on the immune system and on intestinal tumour formation in APC(∆14/+) mice. METHODS: The PAK1 KO APC(∆14/+) mice were generated by cross-breeding of PAK1 KO mice with APC(∆14/+) mice...
June 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28628120/intestinal-cancer-progression-by-mutant-p53-through-the-acquisition-of-invasiveness-associated-with-complex-glandular-formation
#19
M Nakayama, E Sakai, K Echizen, Y Yamada, H Oshima, T-S Han, R Ohki, S Fujii, A Ochiai, S Robine, D C Voon, T Tanaka, M M Taketo, M Oshima
Tumor suppressor TP53 is frequently mutated in colorectal cancer (CRC), and most mutations are missense type. Although gain-of-functions by mutant p53 have been demonstrated experimentally, the precise mechanism for malignant progression in in vivo tumors remains unsolved. We generated Apc(Δ716) Trp53(LSL•R270H) villin-CreER compound mice, in which mutant p53(R270H) was expressed in the intestinal epithelia upon tamoxifen treatment, and examined the intestinal tumor phenotypes and tumor-derived organoids...
June 19, 2017: Oncogene
https://www.readbyqxmd.com/read/28628110/colonic-organoids-derived-from-human-induced-pluripotent-stem-cells-for-modeling-colorectal-cancer-and-drug-testing
#20
Miguel Crespo, Eduardo Vilar, Su-Yi Tsai, Kyle Chang, Sadaf Amin, Tara Srinivasan, Tuo Zhang, Nina H Pipalia, Huanhuan Joyce Chen, Mavee Witherspoon, Miriam Gordillo, Jenny Zhaoying Xiang, Frederick R Maxfield, Steven Lipkin, Todd Evans, Shuibing Chen
With the goal of modeling human disease of the large intestine, we sought to develop an effective protocol for deriving colonic organoids (COs) from differentiated human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs). Extensive gene and immunohistochemical profiling confirmed that the derived COs represent colon rather than small intestine, containing stem cells, transit-amplifying cells, and the expected spectrum of differentiated cells, including goblet and endocrine cells. We applied this strategy to iPSCs derived from patients with familial adenomatous polyposis (FAP-iPSCs) harboring germline mutations in the WNT-signaling-pathway-regulator gene encoding APC, and we generated COs that exhibit enhanced WNT activity and increased epithelial cell proliferation, which we used as a platform for drug testing...
June 19, 2017: Nature Medicine
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