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https://www.readbyqxmd.com/read/28212575/upregulation-of-mucin-glycoprotein-muc1-in-the-progression-to-esophageal-adenocarcinoma-and-therapeutic-potential-with-a-targeted-photoactive-antibody-drug-conjugate
#1
Mohammed Adil Butt, Hayley Pye, Rehan J Haidry, Dahmane Oukrif, Saif-U-Rehman Khan, Ignazio Puccio, Michael Gandy, Halla W Reinert, Ellie Bloom, Mohammed Rashid, Gokhan Yahioglu, Mahendra P Deonarain, Rifat Hamoudi, Manuel Rodriguez-Justo, Marco R Novelli, Laurence B Lovat
BACKGROUND: Mucin glycoprotein 1 (MUC1) is a glycosylated transmembrane protein on epithelial cells. We investigate MUC1 as a therapeutic target in Barrett's epithelium (BE) and esophageal adenocarcinoma (EA) and provide proof of concept for a light based therapy targeting MUC1. RESULTS: MUC1 was present in 21% and 30% of significantly enriched pathways comparing BE and EA to squamous epithelium respectively. MUC1 gene expression was x2.3 and x2.2 higher in BE (p=<0...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212528/the-crispr-cas9%C3%A2-system-efficiently-reverts-the-tumorigenic-ability-of-bcr-abl-in-vitro-and-in-a-xenograft-model-of-chronic-myeloid-leukemia
#2
Ignacio García-Tuñón, María Hernández-Sánchez, José Luis Ordoñez, Veronica Alonso-Pérez, Miguel Álamo-Quijada, Rocio Benito, Carmen Guerrero, Jesús María Hernández-Rivas, Manuel Sánchez-Martín
CRISPR/Cas9 technology was used to abrogate p210 oncoprotein expression in the Boff-p210 cell line, a pro-B line derived from interlukin-3-dependent Baf/3, that shows IL-3-independence arising from the constitutive expression of BCR-ABL p210. Using this approach, pools of Boff-p210-edited cells and single edited cell-derived clones were obtained and functionally studied in vitro. The loss of p210 expression in Boff-p210 cells resulted in the loss of ability to grow in the absence of IL-3, as the Baf/3 parental line, showing significantly increased apoptosis levels...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212503/lactobacillus-buchneri-s-layer-as-carrier-for-an-ara-h-2-derived-peptide-for-peanut-allergen-specific-immunotherapy
#3
Julia Anzengruber, Merima Bublin, Eva Bönisch, Bettina Janesch, Angelika Tscheppe, Matthias L Braun, Eva-Maria Varga, Christine Hafner, Heimo Breiteneder, Christina Schäffer
Peanut allergy is an IgE-mediated severe hypersensitivity disorder. The lack of a treatment of this potentially fatal allergy has led to intensive research on vaccine development. Here, we describe the design and initial characterization of a carrier-bound peptide derived from the most potent peanut allergen, Ara h 2, as a candidate vaccine. Based on the adjuvant capability of bacterial surface (S-) layers, a fusion protein of the S-layer protein SlpB from Lactobacillus buchneri CD034 and the Ara h 2-derived peptide AH3a42 was produced...
February 14, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28212395/delayed-apoptosis-allows-islet-%C3%AE-cells-to-implement-an-autophagic-mechanism-to-promote-cell-survival
#4
Heather L Hayes, Brett S Peterson, Jonathan M Haldeman, Christopher B Newgard, Hans E Hohmeier, Samuel B Stephens
Increased β-cell death coupled with the inability to replicate existing β-cells drives the decline in β-cell mass observed in the progression of both major forms of diabetes. Understanding endogenous mechanisms of islet cell survival could have considerable value for the development of novel strategies to limit β-cell loss and thereby promote β-cell recovery. Insulinoma cells have provided useful insight into β-cell death pathways but observations made in cell lines sometimes fail to translate to primary islets...
2017: PloS One
https://www.readbyqxmd.com/read/28212352/rta-occupancy-of-the-origin-of-lytic-replication-during-murine-gammaherpesvirus-68-reactivation-from-b-cell-latency
#5
Alexis L Santana, Darby G Oldenburg, Varvara Kirillov, Laraib Malik, Qiwen Dong, Roman Sinayev, Kenneth B Marcu, Douglas W White, Laurie T Krug
RTA, the viral Replication and Transcription Activator, is essential for rhadinovirus lytic gene expression upon de novo infection and reactivation from latency. Lipopolysaccharide (LPS)/toll-like receptor (TLR)4 engagement enhances rhadinovirus reactivation. We developed two new systems to examine the interaction of RTA with host NF-kappaB (NF-κB) signaling during murine gammaherpesvirus 68 (MHV68) infection: a latent B cell line (HE-RIT) inducible for RTA-Flag expression and virus reactivation; and a recombinant virus (MHV68-RTA-Bio) that enabled in vivo biotinylation of RTA in BirA transgenic mice...
February 16, 2017: Pathogens
https://www.readbyqxmd.com/read/28212310/presence-of-calcium-lowers-the-expansion-of-bacillus-subtilis-colony-biofilms
#6
Eisha Mhatre, Anandaroopan Sundaram, Theresa Hölscher, Mike Mühlstädt, Jörg Bossert, Ákos T Kovács
Robust colony formation by Bacillus subtilis is recognized as one of the sessile, multicellular lifestyles of this bacterium. Numerous pathways and genes are responsible for the architecturally complex colony structure development. Cells in the biofilm colony secrete extracellular polysaccharides (EPS) and protein components (TasA and the hydrophobin BslA) that hold them together and provide a protective hydrophobic shield. Cells also secrete surfactin with antimicrobial as well as surface tension reducing properties that aid cells to colonize the solid surface...
February 16, 2017: Microorganisms
https://www.readbyqxmd.com/read/28211875/a-hyaluronan-hydrogel-scaffold-based-xeno-free-culture-system-for-ex-vivo-expansion-of-human-corneal-epithelial-stem-cells
#7
D Chen, Y Qu, X Hua, L Zhang, Z Liu, S C Pflugfelder, D-Q Li
PurposeTo develop a hyaluronan hydrogel scaffold-based xeno-free culture system for ex vivo cultivation of human corneal epithelial stem cells (CESCs).Patients and MethodsCESCs were cultivated from donor limbal explants on the HyStem-C Hydrogel bio-scaffold in 12-well plates for 3 weeks. Group A used the traditional supplemented hormonal epidermal medium (SHEM) and group B used the defined SHEM (without fetal bovine serum and toxin A, adding 20% serum replacement). The growth and morphology of the cultured cells were assessed by phase contrast microscope...
February 17, 2017: Eye
https://www.readbyqxmd.com/read/28211314/procedure-for-horizontal-transfer-of-patient-derived-xenograft-tumors-to-eliminate-corynebacterium-bovis
#8
Christopher A Manuel Stacey M Bagby Julie A Reisinger Umarani Pugazhenthi Todd M Pitts Stephen B Keysar John J Arcaroli And Jori K Leszczynski
Human patient-derived xenograft (PDX) tumors, propagated in immunodeficient mice, are rapidly growing in use as amodelfor cancer research. Horizontal transfer between mice, without in vitro cell culture, allows these tumors to retainmany of their unique characteristics from their individual patient of origin. However, the immunodeficient mouse strainsused to grow these tumors are susceptible to numerous opportunistic pathogens, including Corynebacterium bovis. At ourinstitution, 2 in vivo tumor banks of PDX tumors had been maintained within nude mouse colonies enzootically infectedwith C...
February 16, 2017: Journal of the American Association for Laboratory Animal Science: JAALAS
https://www.readbyqxmd.com/read/28211154/kir2dl3-and-the-kir-ligand-groups-hla-a-bw4-and-hla-c2-predict-the-outcome-of-hepatitis-b-virus-infection
#9
Danilo Di Bona, Anna Aiello, Claudia Colomba, Massimo Bilancia, Giulia Accardi, Raffaella Rubino, Lidia Giannitrapani, Antonino Tuttolomondo, Antonio Cascio, Maria Filomena Caiaffa, Sergio Rizzo, Gabriele Di Lorenzo, Giuseppina Candore, Luigi Macchia, Giuseppe Montalto, Calogero Caruso
Killer immunoglobulin-like receptors (KIRs) regulate the activation of Natural Killer cells through their interaction with human leukocyte antigens (HLA). KIR and HLA loci are highly polymorphic and certain HLA-KIR combinations have been found to protect against viral infections. In this study we analyzed whether the KIR/HLA repertoire may influence the course of hepatitis B virus (HBV) infection. Fifty-seven subjects with chronic hepatitis B (CHB), 44 subjects with resolved HBV infection, and 60 healthy uninfected controls (HC) were genotyped for KIR and their HLA ligands...
February 17, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28211079/gata3-expression-in-triple-negative-breast-cancers
#10
David J Byrne, Siddhartha Deb, Elena A Takano, Stephen B Fox
AIMS: GATA-binding protein 3 (GATA3) is a well-studied transcription factor found to be essential in the development of luminal breast epithelium and has been identified in a variety of tumour types including breast and urotheilial carcinomas making it a useful immunohistochemistry marker in the diagnosis of both primary and metastatic disease. METHODS AND RESULTS: We investigated GATA3 protein expression in a 106 primary triple negative breast carcinomas (100 basal-like, 6 non-basal-like) using Cell Marque mouse monoclonal anti-GATA3 (L50-823)...
February 17, 2017: Histopathology
https://www.readbyqxmd.com/read/28211049/low-dose-rituximab-and-concurrent-adjuvant-therapy-for-pemphigus-protocol-and-single-centre-long-term-review-of-nine-patients
#11
Aaron J Robinson, Mi Vu, Gary A Unglik, George A Varigos, Laura Scardamaglia
Pemphigus is an autoimmune B-cell mediated blistering disease associated with significant morbidity and mortality. Rituximab has proven effective for the treatment of steroid-refractory pemphigus, although there is controversy over the optimum dosing protocol. Additionally, effective disease control often requires long-term immunosuppression, even in disease-free periods. We present a case series of a single-centre long-term follow up of nine patients with pemphigus, treated with two 500-mg doses of rituximab separated by 14 days along with concurrent adjuvant therapy...
February 17, 2017: Australasian Journal of Dermatology
https://www.readbyqxmd.com/read/28210987/antiviral-activity-of-ctn-15-34-a-cathelicidin-derived-eicosapeptide-against-infectious-myonecrosis-virus-in-litopenaeus-vannamei-primary-hemocyte-cultures
#12
P R N Vieira-Girão, C B Falcão, I R C B Rocha, H M R Lucena, F H F Costa, G Rádis-Baptista
The shrimp farming has been converted into a mature aquaculture industry dealing with over millions of metric tonnes of processed commodities. Nevertheless, the global shrimp productions are constantly threatened by disease outbreaks, mainly triggered by rapidly disseminating viruses. Infectious myonecrosis virus (IMNV) is one of these epizootic agents affecting shrimp production in Brazil, of which no treatment exists. Herein, the antiviral activity against IMNV of an eicosapeptide, named Ctn[15-34], derived from a member of the cathelicidin family of antimicrobial peptides, was demonstrated...
February 16, 2017: Food and Environmental Virology
https://www.readbyqxmd.com/read/28210941/b-lymphocytes-in-renal-interstitial-fibrosis
#13
REVIEW
Fengge Zhu, Xueyuan Bai, Xiangmei Chen
Fibrosis is defined as an excessive deposition of extracellular matrix (ECM), which leads to the destruction of organ structure and impairment of organ function. Fibrosis occurs not only in kidney but also in lung, liver, heart, and skin. Common pathways of fibrosis are thought to exist. Renal interstitial fibrosis is a complex process that involves multiple molecular signaling and multiple cellular components, in which B cells appear to be one of the emerging important players. B cells may affect fibrosis through cytokine production and through interaction with other cells including fibroblasts, macrophages and T cells...
February 16, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28210822/plasma-dna-methylation-of-p16-and-shp1-in-patients-with-b-cell-non-hodgkin-lymphoma
#14
Kai Ding, Xiaoshuang Chen, Yihao Wang, Hui Liu, Wenjing Song, Lijuan Li, Guojin Wang, Jia Song, Zonghong Shao, Rong Fu
BACKGROUND: Early diagnosis and treatment of non-Hodgkin lymphoma (NHL) are progressively important. It has been shown that aberrant promoter methylation contributes to the development and progression of lymphoma. We tried to explore the effect of methylation of p16 and shp1 genes in plasma in the diagnosis of B-NHL patients. METHODS: The methylation of p16 and shp1 genes in plasma were detected by methylation specific polymerase chain reaction in 103 patients with B-NHL, and compared with peripheral blood leukocytes (PBLs) and formaldehyde-fixed paraffin-embedded (FFPE) tumor tissues...
February 16, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28209992/from-basic-apoptosis-discoveries-to-advanced-selective-bcl-2-family-inhibitors
#15
REVIEW
Avi Ashkenazi, Wayne J Fairbrother, Joel D Leverson, Andrew J Souers
Members of the B cell lymphoma 2 (BCL-2) gene family have a central role in regulating programmed cell death by controlling pro-apoptotic and anti-apoptotic intracellular signals. In cancer, apoptosis evasion through dysregulation of specific BCL-2 family genes is a recurring event; accordingly, selective inhibition of specific anti-apoptotic BCL-2 family proteins represents an exciting therapeutic opportunity. A combination of nuclear magnetic resonance (NMR)-based screening and structure-based drug design has yielded the first bona fide BCL-2 homology 3 (BH3) mimetics, including the BCL-2 and BCL-XL dual antagonist navitoclax, which is the first BCL-2 family inhibitor to show efficacy in patients with cancer...
February 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28209758/atorvastatin-decreases-hbx-induced-phospho-akt-in-hepatocytes-via-p2x-receptors
#16
Aram Ghalali, Javier Martin-Renedo, Johan Hogberg, Ulla Stenius
: Hepatocellular carcinoma (HCC) is rated as the fifth most common malignancy and third in cancer related deaths worldwide. Statins, HMG-CoA reductase inhibitors, are potent cholesterol lowering drugs and recent epidemiological evidence suggests that statins prevent aggressive HCC development. Previous experiments revealed that statins downregulate phosphorylated Akt (pAkt). Here, it is demonstrated that atorvastatin decreases nuclear pAkt levels in pancreatic and lung cancer cell lines within minutes and this rapid effect is mediated by the purinergic P2X receptors...
February 16, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28209737/gaba-cells-in-the-central-nucleus-of-the-amygdala-promote-cataplexy
#17
Matthew B Snow, Jimmy J Fraigne, Gabrielle Thibault-Messier, Victoria L Chuen, Aren Thomasian, Richard L Horner, John Peever
Cataplexy is a hallmark of narcolepsy characterized by the sudden uncontrollable onset of muscle weakness or paralysis during wakefulness. It can occur spontaneously, but is typically triggered by positive emotions such as laughter. Although cataplexy was identified over 130 years ago, its neural mechanism remains unclear. Here, we show that a newly identified GABA circuit within the central nucleus of the amygdala (CeA) promotes cataplexy. We used behavioral, electrophysiological, immunohistochemical, and chemogenetic strategies to selectively target and manipulate CeA activity in narcoleptic (orexin(-/-) ) mice to determine its functional role in controlling cataplexy...
February 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28209491/the-preterm-cervix-reveals-a-transcriptomic-signature-in-the-presence-of-premature-pre-labor-rupture-of-membranes
#18
Sofia Makieva, Aurelija Dubicke, Sara F Rinaldi, Emma Fransson, Gunvor Ekman-Ordeberg, Jane E Norman
BACKGROUND: Premature Pre-labor Rupture of Fetal Membranes (PPROM) accounts for 30% of all premature births and is associated with detrimental long-term infant outcomes. Premature cervical remodeling, facilitated by matrix metalloproteinases (MMPs), may trigger rupture at the zone of the fetal membranes overlying the cervix. The similarities and differences underlying cervical remodeling in PPROM and spontaneous preterm labor with intact membranes (PTL) are unexplored. OBJECTIVES: We aimed a) to perform the first transcriptomic assessment of the preterm human cervix to identify differences between PPROM and PTL and b) to compare the enzymatic activities of MMP-2 and 9 between PPROM and PTL...
February 13, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28209203/crizotinib-associated-renal-cysts-carcs-incidence-and-patterns-of-evolution
#19
Laird B Cameron, Damian H S Jiang, Kate Moodie, Catherine Mitchell, Benjamin Solomon, Bimal Kumar Parameswaran
BACKGROUND: Novel therapeutic agents recently introduced for the treatment of cancer have several unusual side effects. An increased incidence of renal cystic lesions, often with features concerning for malignancy or infection, has been reported in patients with anaplastic lymphoma kinase (ALK) - rearranged advanced non-small cell lung cancer (NSCLC) treated with Crizotinib. Many of these lesions undergo spontaneous resolution despite developing complex features on imaging. We assess the incidence and patterns of evolution of Crizotinib Associated Renal Cysts [CARCs] at our institute and provide histopathology correlation of their benign nature...
February 16, 2017: Cancer Imaging: the Official Publication of the International Cancer Imaging Society
https://www.readbyqxmd.com/read/28208616/immunoinformatics-features-linked-to-leishmania-vaccine-development-data-integration-of-experimental-and-in-silico-studies
#20
Rory C F Brito, Frederico G Guimarães, João P L Velloso, Rodrigo Corrêa-Oliveira, Jeronimo C Ruiz, Alexandre B Reis, Daniela M Resende
Leishmaniasis is a wide-spectrum disease caused by parasites from Leishmania genus. There is no human vaccine available and it is considered by many studies as apotential effective tool for disease control. To discover novel antigens, computational programs have been used in reverse vaccinology strategies. In this work, we developed a validation antigen approach that integrates prediction of B and T cell epitopes, analysis of Protein-Protein Interaction (PPI) networks and metabolic pathways. We selected twenty candidate proteins from Leishmania tested in murine model, with experimental outcome published in the literature...
February 10, 2017: International Journal of Molecular Sciences
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