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https://www.readbyqxmd.com/read/27910858/immunosuppression-in-liver-tumors-opening-the-portal-to-effective-immunotherapy
#1
REVIEW
P Guha, J Reha, S C Katz
We have recently witnessed substantial progress with immunotherapy for selected diseases. Checkpoint inhibitors and chimeric antigen receptor T (CAR-T) cells are among the most promising agents. Whereas much of the early success with CAR-T cells has been demonstrated with hematological malignancies, important barriers remain for the application of CAR-T cell therapies for the management of metastatic solid tumors. The challenges are particularly apparent when considering primary and metastatic tumors in the liver...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27909922/production-of-biologically-active-recombinant-goose-fsh-in-a-single-chain-form-with-a-ctp-linker-sequence
#2
Hui Li, Huanxi Zhu, Qinming Qin, Mingming Lei, Zhendan Shi
FSH is a glycoprotein hormone secreted by the pituitary gland that is essential for gonadal development and reproductive function. In avian reproduction study, especially in avian reproduction hormone study, it is hindered by the lack of biologically active FSH. In order to overcome this shortcoming, we prepared recombinant goose FSH as a single chain molecule and tested its biological activities in the present study. Coding sequences for mature peptides of goose FSH α and β subunits were amplified from goose pituitary cDNA...
December 1, 2016: Molecular Biology Reports
https://www.readbyqxmd.com/read/27909701/immunological-quality-and-performance-of-tumor-vessel-targeting-car-t-cells-prepared-by-mrna-ep-for-clinical-research
#3
Kanako Inoo, Ryo Inagaki, Kento Fujiwara, Shigemi Sasawatari, Takashi Kamigaki, Shinsaku Nakagawa, Naoki Okada
We previously reported that tumor vessel-redirected T cells, which were genetically engineered with chimeric antigen receptor (CAR) specific for vascular endothelial growth factor receptor 2 (VEGFR2), demonstrated significant antitumor effects in various murine solid tumor models. In the present study, we prepared anti-VEGFR2 CAR-T cells by CAR-coding mRNA electroporation (mRNA-EP) and analyzed their immunological characteristics and functions for use in clinical research. The expression of anti-VEGFR2 CAR on murine and human T cells was detected with approximately 100% efficiency for a few days, after peaking 6-12 hours after mRNA-EP...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27909438/donor-specific-regulatory-t-cells-acquired-from-tolerant-mice-bearing-cardiac-allograft-promote-mixed-chimerism-and-prolong-intestinal-allograft-survival
#4
Xiao-Fei Shen, Jin-Peng Jiang, Jian-Jun Yang, Wei-Zhong Wang, Wen-Xian Guan, Jun-Feng Du
The induction of donor-specific transplant tolerance has always been a central problem for small bowel transplantation (SBT), which is thought to be the best therapy for end-stage bowel failure. With the development of new tolerance-inducing strategies, mixed chimerism induced by co-stimulation blockade has become most potent for tolerance of allografts, such as skin, kidney, and heart. However, a lack of clinically available co-stimulation blockers has hindered efficient application in humans. Furthermore, unlike those for other types of solid organ transplantation, strategies to induce robust mixed chimerism for intestinal allografts have not been fully developed...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27909054/identification-of-a-substrate-selective-exosite-within-the-metalloproteinase-anthrax-lethal-factor
#5
Allison B Goldberg, Eunice Cho, Chad J Miller, Hua Jane Lou, Benjamin E Turk
The metalloproteinase anthrax lethal factor (LF) is secreted by Bacillus anthracis to promote disease virulence through disruption of host signaling pathways. LF is a highly specific protease, exclusively cleaving mitogen-activated protein kinase kinases (MKKs) and rodent NACHT leucine-rich repeat and pyrin domain containing protein 1B (NLRP1B). How LF achieves such restricted substrate specificity is not understood. Previous studies have suggested the existence of an exosite interaction between LF and MKKs that promotes cleavage efficiency and specificity...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27907215/cd8-t-cells-induce-fatal-brainstem-pathology-during-cerebral-malaria-via-luminal-antigen-specific-engagement-of-brain-vasculature
#6
Phillip A Swanson, Geoffrey T Hart, Matthew V Russo, Debasis Nayak, Takele Yazew, Mirna Peña, Shahid M Khan, Chris J Janse, Susan K Pierce, Dorian B McGavern
Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection that results in thousands of deaths each year, mostly in African children. The in vivo mechanisms underlying this fatal condition are not entirely understood. Using the animal model of experimental cerebral malaria (ECM), we sought mechanistic insights into the pathogenesis of CM. Fatal disease was associated with alterations in tight junction proteins, vascular breakdown in the meninges / parenchyma, edema, and ultimately neuronal cell death in the brainstem, which is consistent with cerebral herniation as a cause of death...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27907167/infusion-advancing-discovery-of-fusion-genes-and-chimeric-transcripts-from-deep-rna-sequencing-data
#7
Konstantin Okonechnikov, Aki Imai-Matsushima, Lukas Paul, Alexander Seitz, Thomas F Meyer, Fernando Garcia-Alcalde
Analysis of fusion transcripts has become increasingly important due to their link with cancer development. Since high-throughput sequencing approaches survey fusion events exhaustively, several computational methods for the detection of gene fusions from RNA-seq data have been developed. This kind of analysis, however, is complicated by native trans-splicing events, the splicing-induced complexity of the transcriptome and biases and artefacts introduced in experiments and data analysis. There are a number of tools available for the detection of fusions from RNA-seq data; however, certain differences in specificity and sensitivity between commonly used approaches have been found...
2016: PloS One
https://www.readbyqxmd.com/read/27907031/in-vitro-pre-clinical-validation-of-suicide-gene-modified-anti-cd33-redirected-chimeric-antigen-receptor-t-cells-for-acute-myeloid-leukemia
#8
Kentaro Minagawa, Muhammad O Jamil, Mustafa Al-Obaidi, Larisa Pereboeva, Donna Salzman, Harry P Erba, Lawrence S Lamb, Ravi Bhatia, Shin Mineishi, Antonio Di Stasi
BACKGROUND: Approximately fifty percent of patients with acute myeloid leukemia can be cured with current therapeutic strategies which include, standard dose chemotherapy for patients at standard risk of relapse as assessed by cytogenetic and molecular analysis, or high-dose chemotherapy with allogeneic hematopoietic stem cell transplant for high-risk patients. Despite allogeneic hematopoietic stem cell transplant about 25% of patients still succumb to disease relapse, therefore, novel strategies are needed to improve the outcome of patients with acute myeloid leukemia...
2016: PloS One
https://www.readbyqxmd.com/read/27906032/infection-of-rhesus-macaques-with-a-pool-of-simian-immunodeficiency-virus-with-the-envelope-genes-from-acute-hiv-1-infections
#9
Kendall C Krebs, Meijuan Tian, Mohammed Asmal, Binhua Ling, Kenneth Nelson, Kenneth Henry, Richard Gibson, Yuejin Li, Weining Han, Robin J Shattock, Ronald S Veazey, Norman Letvin, Eric J Arts, Yong Gao
BACKGROUND: New simian-human immunodeficiency chimeric viruses with an HIV-1 env (SHIVenv) are critical for studies on HIV pathogenesis, vaccine development, and microbicide testing. Macaques are typically exposed to single CCR5-using SHIVenv which in most instances does not reflect the conditions during acute/early HIV infection (AHI) in humans. Instead of individual and serial testing new SHIV constructs, a pool of SHIVenv_B derived from 16 acute HIV-1 infections were constructed using a novel yeast-based SHIV cloning approach and then used to infect macaques...
November 25, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27905838/engineering-hiv-specific-immunity-with-chimeric-antigen-receptors
#10
Scott G Kitchen, Jerome A Zack
HIV remains a highly important public health and clinical issue despite many recent advances in attempting to develop a cure, which has remained elusive for most people infected with HIV. HIV disease can be controlled with pharmacologic therapies; however, these treatments are expensive, may have severe side effects, and are not curative. Consequently, an improved means to control or eliminate HIV replication is needed. Cytotoxic T lymphocytes (CTLs) play a critical role in controlling viral replication and are an important part in the ability of the immune response to eradicate most viral infections...
December 2016: AIDS Patient Care and STDs
https://www.readbyqxmd.com/read/27905258/hla-mismatched-haploidentical-transplantation-using-low-dose-anti-thymocyte-globulin-atg-thymoglobulin
#11
Shinichi Kako, Yu Akahoshi, Naonori Harada, Hirofumi Nakano, Kazuaki Kameda, Tomotaka Ugai, Ryoko Yamasaki, Hidenori Wada, Yuko Ishihara, Koji Kawamura, Kana Sakamoto, Miki Sato, Masahiro Ashizawa, Kiriko Terasako-Saito, Shun-Ichi Kimura, Misato Kikuchi, Hideki Nakasone, Rie Yamazaki, Junya Kanda, Yoshinobu Kanda
Objectives To clarify optimal strategies for human leukocyte antigen (HLA)-mismatched haploidentical hematopoietic stem cell transplantation (HSCT). Methods Twelve patients who underwent HSCT from a haploidentical related donor using low-dose thymoglobulin were analyzed retrospectively. Thymoglobulin was added to conditioning regimens at 2.5 mg/kg/day for 2 days (days -4 and -3). Prophylaxis against graft-versus-host disease (GVHD) was performed with cyclosporine and methotrexate. Results The median age of the patients was 33 years...
December 1, 2016: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/27903760/interactions-between-intersubunit-transmembrane-domains-regulate-the-chaperone-dependent-degradation-of-an-oligomeric-membrane-protein
#12
Teresa M Buck, Alexa S Jordahl, Megan E Yates, Mike Preston, Emily Cook, Thomas R Kleyman, Jeffrey L Brodsky
The Epithelial Sodium Channel (ENaC) in kidney regulates blood pressure through control of sodium and volume homeostasis, and in lung ENaC regulates the volume of airway and alveolar fluids.  ENaC is a heterotrimer of homologous α-, β-, and γ-subunits, and assembles in the Endoplasmic Reticulum (ER) before it traffics and functions at the plasma membrane. Improperly folded or orphaned ENaC subunits are subject to ER quality control and targeted for ER associated degradation (ERAD). We previously established that a conserved, ER lumenal, molecular chaperone, Lhs1/GRP170, selects αENaC, but not β- or γENaC, for degradation when the ENaC subunits were individually expressed...
November 30, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27903531/dream-plays-an-important-role-in-platelet-activation-and-thrombogenesis
#13
Kyungho Kim, Alan Tseng, Andrew Barazia, Joseph E Italiano, Jaehyung Cho
Downstream regulatory element antagonist modulator (DREAM), a transcriptional repressor, is known to modulate pain responses. However, it is unknown whether DREAM is expressed in anucleate platelets and plays a role in thrombogenesis. By using intravital microscopy with DREAM-null mice and their bone marrow chimeras, we demonstrated that both hematopoietic and non-hematopoietic cell DREAM are required for platelet thrombus formation following laser-induced arteriolar injury. In a FeCl3-induced thrombosis model, we found that compared to WT control and non-hematopoietic DREAM knockout (KO) mice, DREAM KO control and hematopoietic DREAM KO mice showed a significant delay in time to occlusion...
November 30, 2016: Blood
https://www.readbyqxmd.com/read/27902881/the-chimeric-nature-of-the-genomes-of-marine-magnetotactic-coccoid-ovoid-bacteria-defines-a-novel-group-of-proteobacteria
#14
Boyang Ji, Sheng-Da Zhang, Wei-Jia Zhang, Zoe Rouy, François Alberto, Claire-Lise Santini, Sophie Mangenot, Séverine Gagnot, Nadège Philippe, Nathalie Pradel, Lichen Zhang, Sébastien Tempel, Ying Li, Claudine Médigue, Bernard Henrissat, Pedro M Coutinho, Valérie Barbe, Emmanuel Talla, Long-Fei Wu
Magnetotactic bacteria (MTB) are a group of phylogenetically and physiologically diverse Gram-negative bacteria that synthesize intracellular magnetic crystals named magnetosomes. MTB are affiliated with three classes of Proteobacteria phylum, Nitrospirae phylum, Omnitrophica phylum and probably with the candidate phylum Latescibacteria. The evolutionary origin and physiological diversity of MTB compared to other bacterial taxonomic groups remain to be illustrated. Here, we analyzed the genome of the marine magneto-ovoid strain MO-1 and found that it is closely related to Magnetococcus marinus MC-1...
November 30, 2016: Environmental Microbiology
https://www.readbyqxmd.com/read/27902705/neuronal-ndrg4-is-essential-for-nodes-of-ranvier-organization-in-zebrafish
#15
Laura Fontenas, Flavia De Santis, Vincenzo Di Donato, Cindy Degerny, Béatrice Chambraud, Filippo Del Bene, Marcel Tawk
Axon ensheathment by specialized glial cells is an important process for fast propagation of action potentials. The rapid electrical conduction along myelinated axons is mainly due to its saltatory nature characterized by the accumulation of ion channels at the nodes of Ranvier. However, how these ion channels are transported and anchored along axons is not fully understood. We have identified N-myc downstream-regulated gene 4, ndrg4, as a novel factor that regulates sodium channel clustering in zebrafish. Analysis of chimeric larvae indicates that ndrg4 functions autonomously within neurons for sodium channel clustering at the nodes...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27902397/vesivirus-2117-capsids-more-closely-resemble-sapovirus-and-lagovirus-particles-than-other-known-vesivirus-structures
#16
Michaela Conley, Edward Emmott, Richard Orton, David Taylor, Daniel Carneiro, Kazuyoshi Murata, Ian Goodfellow, Grant Hansman, David Bhella
Vesivirus 2117 is an adventitious agent that in 2009, was identified as a contaminant of CHO cells propagated in bioreactors at a pharmaceutical manufacturing plant belonging to Genzyme. The consequent interruption in supply of Fabrazyme and Cerezyme (drugs used to treat Fabry and Gaucher disease respectively), caused significant economic losses. Vesivirus 2117 is a member of the Caliciviridae; a family of small icosahedral viruses encoding a positive sense RNA genome. We have used cryo-electron microscopy and three dimensional image reconstruction to calculate a structure of vesivirus 2117 virus like particles as well as feline calicivirus and a chimeric sapovirus...
November 14, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27901085/wide-variation-in-susceptibility-of-transmitted-founder-hiv-1-subtype-c-isolates-to-protease-inhibitors-and-association-with-in-vitro-replication-efficiency
#17
Katherine A Sutherland, Dami A Collier, Daniel T Claiborne, Jessica L Prince, Martin J Deymier, Richard A Goldstein, Eric Hunter, Ravindra K Gupta
The gag gene is highly polymorphic across HIV-1 subtypes and contributes to susceptibility to protease inhibitors (PI), a critical class of antiretrovirals that will be used in up to 2 million individuals as second-line therapy in sub Saharan Africa by 2020. Given subtype C represents around half of all HIV-1 infections globally, we examined PI susceptibility in subtype C viruses from treatment-naïve individuals. PI susceptibility was measured in a single round infection assay of full-length, replication competent MJ4/gag chimeric viruses, encoding the gag gene and 142 nucleotides of pro derived from viruses in 20 patients in the Zambia-Emory HIV Research Project acute infection cohort...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899645/efficient-targeted-dna-methylation-with-chimeric-dcas9-dnmt3a-dnmt3l-methyltransferase
#18
Peter Stepper, Goran Kungulovski, Renata Z Jurkowska, Tamir Chandra, Felix Krueger, Richard Reinhardt, Wolf Reik, Albert Jeltsch, Tomasz P Jurkowski
DNA methylation plays a critical role in the regulation and maintenance of cell-type specific transcriptional programs. Targeted epigenome editing is an emerging technology to specifically regulate cellular gene expression in order to modulate cell phenotypes or dissect the epigenetic mechanisms involved in their control. In this work, we employed a DNA methyltransferase Dnmt3a-Dnmt3L construct fused to the nuclease-inactivated dCas9 programmable targeting domain to introduce DNA methylation into the human genome specifically at the EpCAM, CXCR4 and TFRC gene promoters...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899596/chitars-3-1-the-enhanced-chimeric-transcripts-and-rna-seq-database-matched-with-protein-protein-interactions
#19
Alessandro Gorohovski, Somnath Tagore, Vikrant Palande, Assaf Malka, Dorith Raviv-Shay, Milana Frenkel-Morgenstern
Discovery of chimeric RNAs, which are produced by chromosomal translocations as well as the joining of exons from different genes by trans-splicing, has added a new level of complexity to our study and understanding of the transcriptome. The enhanced ChiTaRS-3.1 database (http://chitars.md.biu.ac.il) is designed to make widely accessible a wealth of mined data on chimeric RNAs, with easy-to-use analytical tools built-in. The database comprises 34 922: chimeric transcripts along with 11 714: cancer breakpoints...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899251/improved-breast-cancer-cell-specific-intracellular-drug-delivery-and-therapeutic-efficacy-by-coupling-decoration-with-cell-penetrating-peptide-and-sp90-peptide
#20
Li-Qiang Fan, Guo-Xiu Du, Peng-Fei Li, Ming-Wei Li, Yao Sun, Li-Ming Zhao
Lack of satisfactory specificity towards tumor cells and poor intracellular delivery efficacy are the major drawbacks with conventional cancer chemotherapy. Conjugated anticancer drugs to targeting moieties e.g. to peptides with the ability to recognize cancer cells and to cell penetrating peptide can improve these characteristics, respectively. Combining a tumor homing peptide with an appropriate cell-penetrating peptide can enhance the tumor-selective internalization efficacy of the carrying cargo molecules...
November 26, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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