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https://www.readbyqxmd.com/read/29222400/nkg2d-based-car-t-cells-and-radiotherapy-exert-synergistic-efficacy-in-glioblastoma
#1
Tobias Weiss, Michael Weller, Matthias Guckenberger, Charles L Sentman, Patrick Roth
Chimeric antigen receptor (CAR) T cell therapy is an emerging immunotherapy against several malignancies including glioblastoma, the most common and most aggressive malignant primary brain tumor in adults. The challenges in solid tumor immunotherapy comprise heterogenously expressed tumor target antigens and restricted trafficking of CAR T cells to and impaired long-term persistence at the tumor site, as well as the unaddressed integration of CAR T cell therapy into conventional anti-cancer treatments. We addressed these questions using a NKG2D-based chimeric antigen receptor construct (chNKG2D) in fully immunocompetent orthotopic glioblastoma mouse models...
December 8, 2017: Cancer Research
https://www.readbyqxmd.com/read/29222325/cells-to-prevent-treat-relapse-following-allogeneic-stem-cell-transplantation
#2
REVIEW
Andrew C Dietz, Alan S Wayne
Relapse of cancer remains one of the primary causes of treatment failure and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). A multitude of approaches have been used in the management of posttransplant relapse. This review focuses on recent data with cellular therapies designed to treat or prevent posttransplant relapse of hematologic malignancies, although many of these therapeutic approaches also have applications to solid tumors and in the nontransplant setting. Currently available cell therapies include second transplant, natural killer cells, monocyte-derived dendritic cell vaccines, and lymphocytes via donor lymphocyte infusion, antigen-primed cytotoxic T lymphocytes, cytokine-induced killer cells, marrow-infiltrating lymphocytes, and chimeric antigen receptor T cells...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222313/developing-t-cell-therapies-for-lymphoma-without-receptor-engineering
#3
REVIEW
Melanie Grant, Catherine M Bollard
T-cell therapy has emerged from the bench for the treatment of patients with lymphoma. Responses to T-cell therapeutics are regulated by multiple factors, including the patient's immune system status and disease stage. Outside of engineering of chimeric antigen receptors and artificial T-cell receptors, T-cell therapy can be mediated by ex vivo expansion of antigen-specific T cells targeting viral and/or nonviral tumor-associated antigens. These approaches are contributing to enhanced clinical responses and overall survival...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222264/incorporation-of-nonchemotherapeutic-agents-in-pediatric-acute-lymphoblastic-leukemia
#4
REVIEW
Lewis B Silverman
With current available therapies, the prognosis for most children and adolescents with acute lymphoblastic leukemia (ALL) is favorable. However, the multiagent chemotherapy regimens used to treat newly diagnosed patients are associated with many acute and long-term complications, and therapy for relapsed disease is intensive and suboptimally effective. Over the last decade, several nonchemotherapeutic approaches have been evaluated, with the goal of identifying more effective, less toxic therapies that can be used in conjunction with, or even replace, current regimens...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29220811/synergistic-effect-of-the-enzyme-complexes-comprising-agarase-carrageenase-and-neoagarobiose-hydrolase-on-degradation-of-the-red-algae
#5
Dae Hee Kang, Seung Kyou You, Young-Chul Joo, Sang Kyu Shin, Jeong Eun Hyeon, Sung Ok Han
In the practice of converting red algae biomass into biofuel or valuable biomaterials, the critical step is the decomposition process of the agarose to give fermentable monomeric sugars. In this study, we selected three enzymes such as agarase, carrageenase and neoagarobiose hydrolase to inducible the simultaneous hydrolysis of the major substrates such as agar and carrageenan constituting the pretreated red algae, and expressed the chimeric enzymes and formed a complexes through optimization of addition ratio...
December 2, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/29220536/cd36-deficiency-attenuates-immune-mediated-hepatitis-in-mice-by-modulating-the-proapoptotic-effects-of-cxcl10
#6
Che Xu, Chen Zhang, Jie Ji, Chao Wang, Jing Yang, Biao Geng, Ting Zhao, Hong Zhou, Xianmin Mu, Jinshun Pan, Shi Hu, Yuanfang Lv, Xingguo Chen, Hao Wen, Qiang You
The scavenger receptor, CD36, recognizes a diverse set of ligands, and has been implicated in a wide variety of normal and pathological processes, including lipid metabolism, angiogenesis, atherosclerosis, and phagocytosis. In particular, recent findings have demonstrated its crucial functions in sterile inflammation and tumor metastasis. However, the role of CD36 in immune-mediated hepatitis remains unclear. Concanavalin A (Con A)-induced liver injury is a well-established experimental T cell-mediated hepatitis...
December 8, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29220291/emerging-targeted-and-immune-based-therapies-in-sarcoma
#7
Seth M Pollack, Matthew Ingham, Matthew B Spraker, Gary K Schwartz
Soft tissue and bone sarcomas are malignancies of mesenchymal origin, and more than 50 subtypes are defined. For most sarcomas, locally advanced or unresectable disease is still treated with cytotoxic chemotherapy. Recently, our understanding of subtype-specific cancer biology has expanded, and it has revealed distinct molecular alterations responsible for tumor initiation and progression. These findings have motivated the development of targeted therapies that are being evaluated in subtype-specific or biomarker-driven clinical trials...
December 8, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29218853/rna-sequencing-identifies-novel-greb1-ncoa2-fusion-gene-in-a-uterine-sarcoma-with-the-chromosomal-translocation-t-2-8-p25-q13
#8
Marta Brunetti, Ioannis Panagopoulos, Ludmila Gorunova, Ben Davidson, Sverre Heim, Francesca Micci
Sarcomas account for 3% of all uterine malignancies and many of them are characterized by acquired, specific fusion genes whose detection has increased pathogenetic knowledge and diagnostic precision. We describe a novel fusion gene, GREB1-NCOA2, detected by transcriptome sequencing and validated by RT-PCR and Sanger sequencing in an undifferentiated uterine sarcoma. The chimeric transcript was an in-frame fusion between exon 3 of GREB1 and exon 15 of NCOA2. The fusion is reported here for the first time, but it involves the GREB1 gene, an important promoter of tumor growth and progression, and NCOA2 which is known to be involved in transcriptional regulation...
December 8, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/29218849/reconstruction-of-full-thickness-cheek-defect-with-chimeric-facial-artery-free-flap-a-case-report
#9
Olindo Massarelli, Luigi Angelo Vaira, Roberta Gobbi, Giovanni Dell'aversana Orabona, Giacomo De Riu
Full-thickness cheek defects represent a difficult challenge for reconstructive surgeons. Multiple techniques have been described, including local, regional, and free flaps. In this report, the reconstruction of a through and through left cheek defect, resulting from a self-inflicted gunshot injury, with a chimeric facial artery free flap is presented. The patient underwent reconstruction with a chimeric full-thickness facial artery free flap, with 9 × 3 cm diameter skin paddle and a 6 × 5 cm myomucosal paddle, was harvested on the contralateral cheek with a 7-cm length of facial pedicle...
December 8, 2017: Microsurgery
https://www.readbyqxmd.com/read/29217780/from-transplant-to-novel-cellular-therapies-in-multiple-myeloma-emn-guidelines-and-future-perspectives
#10
Francesca Gay, Monika Engelhardt, Evangelos Terpos, Ralph Wäsch, Luisa Giaccone, Holger W Auner, Jo Caers, Martin Gramatzki, Niels van de Donk, Stefania Oliva, Elena Zamagni, Laurent Garderet, Christian Straka, Roman Hajek, Heinz Ludwig, Hermann Einsele, Meletios Dimopoulos, Mario Boccadoro, Nicolaus Kröger, Michele Cavo, Hartmut Goldschmidt, Benedetto Bruno, Pieter Sonneveld
Survival of myeloma patients has greatly improved with the use of autologous stem cell transplantation and novel agents, such as proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies. Compared to bortezomib- and lenalidomide-based regimens alone, the addition of high-dose melphalan followed by autologous transplantation significantly improves progression-free survival; although an overall survival benefit was not observed in all trials. Moreover, follow-up of recent trials is still too short to show any difference in survival...
December 7, 2017: Haematologica
https://www.readbyqxmd.com/read/29217660/chimeric-pneumoviridae-fusion-proteins-as-immunogens-to-induce-cross-neutralizing-antibody-responses
#11
Eduardo Olmedillas, Olga Cano, Isidoro Martínez, Daniel Luque, María C Terrón, Jason S McLellan, José A Melero, Vicente Más
Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV), two members of the Pneumoviridae family, account for the majority of severe lower respiratory tract infections worldwide in very young children. They are also a frequent cause of morbidity and mortality in the elderly and immunocompromised adults. High levels of neutralizing antibodies, mostly directed against the viral fusion (F) glycoprotein, correlate with protection against either hRSV or hMPV However, no cross-neutralization is observed in polyclonal antibody responses raised after virus infection or immunization with purified F proteins...
December 7, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29217157/functional-histamine-h3-and-adenosine-a2a-receptor-heteromers-in-recombinant-cells-and-rat-striatum
#12
Ricardo Márquez-Gómez, Meridith T Robins, Citlaly Gutiérrez-Rodelo, Juan-Manuel Arias, Jesús-Alberto Olivares-Reyes, Richard M van Rijn, José-Antonio Arias-Montaño
In the striatum, histamine H3 receptors (H3Rs) are co-expressed with adenosine A2A receptors (A2ARs) in the cortico-striatal glutamatergic afferents and the GABAergic medium-sized spiny neurons that originate from the indirect pathway of the basal ganglia. This location allows H3Rs and A2ARs to regulate the striatal GABAergic and glutamatergic transmission. However, whether these receptors can physically interact has not yet been assessed. To test this hypothesis, a heteromer-selective in vitro assay was used to detect functional complementation between a chimeric A2AR302-Gαqi4 and wild-type H3Rs in transfected HEK-293 cells...
December 4, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29217154/production-of-a-chimeric-protein-and-its-potential-application-in-sero-diagnosis-of-mycoplasma-hominis-infection
#13
Saman Saadat, Mohammad M Sajadi, Mohammad Yousef Alikhani, Zahra Rikhtegaran Tehrani, Rasoul Yousefi Mashouf
INTRODUCTION: Mycoplasma hominis is an opportunistic pathogen of the human genital tract. Detection of antibodies against this organism in human serum or plasma is theoretically unreliable because of high variation in bacterial surface antigens. In this study, we applied the bioinformatics tools to design a chimeric protein constructed of specific, conserved and predicted immuno-dominant epitopes from two different membrane proteins, P120 and P80. MATERIAL AND METHODS: Linear B-cell epitopes of P120 and P80 were predicted and evaluated by bioinformatics tools and the designed chimeric protein was expressed in Escherichia coli...
December 4, 2017: Journal of Microbiological Methods
https://www.readbyqxmd.com/read/29216507/chimeric-hcmv-hsv-1-and-%C3%AE-%C3%AE-134-5-oncolytic-herpes-simplex-virus-elicit-immune-mediated-antigliomal-effect-and-antitumor-memory
#14
Mohammed G Ghonime, Josh Jackson, Amish Shah, Justin Roth, Mao Li, Ute Saunders, Jennifer Coleman, G Yancey Gillespie, James M Markert, Kevin A Cassady
Malignant gliomas are the most common primary brain tumor and are characterized by rapid and highly invasive growth. Because of their poor prognosis, new therapeutic strategies are needed. Oncolytic virotherapy (OV) is a promising strategy for treating cancer that incorporates both direct viral replication mediated and immune mediated mechanisms to kill tumor cells. C134 is a next generation Δγ134.5 oHSV-1 with improved intratumoral viral replication. It remains safe in the CNS environment by inducing early IFN signaling which restricts its replication in non-malignant cells...
December 4, 2017: Translational Oncology
https://www.readbyqxmd.com/read/29215635/mapping-the-small-rna-interactome-in-bacteria-using-ril-seq
#15
Sahar Melamed, Raya Faigenbaum-Romm, Asaf Peer, Niv Reiss, Omer Shechter, Amir Bar, Yael Altuvia, Liron Argaman, Hanah Margalit
Small RNAs (sRNAs) are major post-transcriptional regulators of gene expression in bacteria. To enable transcriptome-wide mapping of bacterial sRNA-target pairs, we developed RIL-seq (RNA interaction by ligation and sequencing). RIL-seq is an experimental-computational methodology for capturing sRNA-target interactions in vivo that takes advantage of the mutual binding of the sRNA and target RNA molecules to the RNA chaperone protein Hfq. The experimental part of the protocol involves co-immunoprecipitation of Hfq and bound RNAs, ligation of RNAs, library preparation and sequencing...
January 2018: Nature Protocols
https://www.readbyqxmd.com/read/29213270/nanobodies-and-nanobody-based-human-heavy-chain-antibodies-as-antitumor-therapeutics
#16
REVIEW
Peter Bannas, Julia Hambach, Friedrich Koch-Nolte
Monoclonal antibodies have revolutionized cancer therapy. However, delivery to tumor cells in vivo is hampered by the large size (150 kDa) of conventional antibodies. The minimal target recognition module of a conventional antibody is composed of two non-covalently associated variable domains (VH and VL). The proper orientation of these domains is mediated by their hydrophobic interface and is stabilized by their linkage to disulfide-linked constant domains (CH1 and CL). VH and VL domains can be fused via a genetic linker into a single-chain variable fragment (scFv)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29212954/inhibition-of-akt-signaling-uncouples-t-cell-differentiation-from-expansion-for-receptor-engineered-adoptive-immunotherapy
#17
Christopher A Klebanoff, Joseph G Crompton, Anthony J Leonardi, Tori N Yamamoto, Smita S Chandran, Robert L Eil, Madhusudhanan Sukumar, Suman K Vodnala, Jinhui Hu, Yun Ji, David Clever, Mary A Black, Devikala Gurusamy, Michael J Kruhlak, Ping Jin, David F Stroncek, Luca Gattinoni, Steven A Feldman, Nicholas P Restifo
Adoptive immunotherapies using T cells genetically redirected with a chimeric antigen receptor (CAR) or T cell receptor (TCR) are entering mainstream clinical practice. Despite encouraging results, some patients do not respond to current therapies. In part, this phenomenon has been associated with infusion of reduced numbers of early memory T cells. Herein, we report that AKT signaling inhibition is compatible with CAR and TCR retroviral transduction of human T cells while promoting a CD62L-expressing central memory phenotype...
December 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/29212740/il-23-interleukin-23-producing-conventional-dendritic-cells-control-the-detrimental-il-17-interleukin-17-response-in-stroke
#18
Mathias Gelderblom, Mattia Gallizioli, Peter Ludewig, Vivien Thom, Priyadharshini Arunachalam, Björn Rissiek, Christian Bernreuther, Markus Glatzel, Thomas Korn, Thiruma Valavan Arumugam, Jan Sedlacik, Christian Gerloff, Eva Tolosa, Anna M Planas, Tim Magnus
BACKGROUND AND PURPOSE: Inflammatory mechanisms can exacerbate ischemic tissue damage and worsen clinical outcome in patients with stroke. Both αβ and γδ T cells are established mediators of tissue damage in stroke, and the role of dendritic cells (DCs) in inducing the early events of T cell activation and differentiation in stroke is not well understood. METHODS: In a murine model of experimental stroke, we defined the immune phenotype of infiltrating DC subsets based on flow cytometry of surface markers, the expression of ontogenetic markers, and cytokine levels...
December 6, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29212222/antitumor-activity-of-a-newly-developed-monoclonal-antibody-against-ror1-in-ovarian-cancer-cells
#19
Zhengna Yin, Mengyun Gao, Sasa Chu, Yiping Su, Chunping Ye, Yiquan Wang, Zhuanqin Pan, Zhuming Wang, Huilin Zhang, Hua Tong, Jin Zhu
Receptor-tyrosine-kinase-like Orphan Receptor 1 (ROR1) is a tyrosine-protein kinase transmembrane receptor and ROR1 overexpression is associated with a poor prognosis in various cancers, including ovarian cancer. Targeting of ROR1 has been evaluated as a novel cancer therapy strategy. This study developed a novel chimeric anti-ROR1 Fab antibody (named ROR1-cFab) and then assessed the antitumor activity of this antibody in ovarian cancer cells, an in vitro model of preclinical cancer therapy. A ROR1-cFab prokaryotic expression vector was constructed from positive fusion cells (splenocytes from mice with high ROR1 immune titers were fused with myeloma cells) after three rounds of sub-clone affinity screening...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29212218/optimized-guide-rna-structure-for-genome-editing-via-cas9
#20
Jianyong Xu, Wei Lian, Yuning Jia, Lingyun Li, Zhong Huang
The genome editing tool Cas9-gRNA (guide RNA) has been successfully applied in different cell types and organisms with high efficiency. However, more efforts need to be made to enhance both efficiency and specificity. In the current study, we optimized the guide RNA structure of Streptococcus pyogenes CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas (CRISPR-associated) system to improve its genome editing efficiency. Comparing with the original functional structure of guide RNA, which is composed of crRNA and tracrRNA, the widely used chimeric gRNA has shorter crRNA and tracrRNA sequence...
November 7, 2017: Oncotarget
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