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https://www.readbyqxmd.com/read/29237129/zap-70-in-signaling-biology-and-disease
#1
Byron B Au-Yeung, Neel H Shah, Lin Shen, Arthur Weiss
T cells possess an array of functional capabilities important for host defense against pathogens and tumors. T cell effector functions require the T cell antigen receptor (TCR). The TCR has no intrinsic enzymatic activity, and thus signal transduction from the receptor relies on additional signaling molecules. One such molecule is the cytoplasmic tyrosine kinase ZAP-70, which associates with the TCR complex and is required for initiating the canonical biochemical signal pathways downstream of the TCR. In this article, we describe recent structure-based insights into the regulation and substrate specificity of ZAP-70, and then we review novel methods for determining the role of ZAP-70 catalytic activity-dependent and -independent signals in developing and mature T cells...
December 13, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/29192596/detection-of-ras-mutations-in-circulating-tumor-cells-applications-in-colorectal-cancer-and-prospects
#2
Jérôme Alexandre Denis, Jean-Marc Lacorte
The somatic mutations in the RAS genes (KRAS and NRAS) are widely associated with non-response to immunotherapies targeting the epidermal growth factor receptor in metastatic colorectal cancer. The detection of these mutations is carried out from tissue biopsies and become mandatory to prescribe these treatments. Nethertheless, this analysis is not possible in about 25% of cases and the development of alternative methods is therefore required. Among them, the search for mutations directly in the blood of patients are promising approaches...
December 1, 2017: Annales de Biologie Clinique
https://www.readbyqxmd.com/read/29180875/effective-treatment-of-low-dose-decitabine-in-myelodysplastic-syndrome-myeloproliferative-neoplasms
#3
Xingnong Ye, Dan Chen, Yan Zheng, Xiaoqiong Zhu, Junkai Fu, Jian Huang
Objective: Primary myelofibrosis (PMF) is one of the Philadelphia negative myeloproliferative neoplasms (MPN). The main clinical features are obvious physical symptoms and symptomatic splenomegaly. It may be converse to leukemia and has a shortened life expectancy. Nowadays, the therapy for PMF is aimed at maintaining comfort and there is no curative treatment. PMF with myelodysplastic syndrome (MDS), called MDS/MPN-u, is rare and the treatment is complex. In this study, we want to discuss an effective treatment for MDS/MPN via a case report and literature review...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29180489/downregulation-of-nfat3-due-to-lack-of-t-box-transcription-factor-tbx5-is-crucial-for-cytokine-expression-in-t-cells
#4
Osamu Kaminuma, Noriko Kitamura, Yasumasa Nishito, Soichi Nemoto, Hideki Tatsumi, Akio Mori, Takachika Hiroi
The NFAT family transcription factors play crucial roles in immunological and other biological activities. NFAT3 is rarely expressed in T cells, and the mechanisms and significance of the specific NFAT3 downregulation in T cells have been unknown. In human CD4+ T cells, overexpression of NFAT1 and NFAT3 enhanced and suppressed IL-2 expression, respectively. NFAT3 downregulation in Jurkat cells using RNA interference technology augmented IL-2 expression, whereas a knockdown of NFAT1, NFAT2, and NFAT4 suppressed it...
November 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29081765/breast-cancer-vaccines-new-insights
#5
REVIEW
Rosaria Benedetti, Carmela Dell'Aversana, Cristina Giorgio, Roberta Astorri, Lucia Altucci
Breast cancer (BC) is a persistent global challenge for its high frequency in women (although it seldom occurs in men), due to the large diffusion of risk factors and gene mutations, and for its peculiar biology and microenvironment. To date, BC can benefit from different therapeutic strategies involving surgery, ablation, chemotherapy, radiotherapy, and more specific approaches such as hormone therapy and the administration of various substances impairing cancer growth, aggressivity, and recurrence with different modalities...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28879168/the-oncopig-cancer-model-an-innovative-large-animal-translational-oncology-platform
#6
REVIEW
Kyle M Schachtschneider, Regina M Schwind, Jordan Newson, Nickolas Kinachtchouk, Mark Rizko, Nasya Mendoza-Elias, Paul Grippo, Daniel R Principe, Alex Park, Nana H Overgaard, Gregers Jungersen, Kelly D Garcia, Ajay V Maker, Laurie A Rund, Howard Ozer, Ron C Gaba, Lawrence B Schook
Despite an improved understanding of cancer molecular biology, immune landscapes, and advancements in cytotoxic, biologic, and immunologic anti-cancer therapeutics, cancer remains a leading cause of death worldwide. More than 8.2 million deaths were attributed to cancer in 2012, and it is anticipated that cancer incidence will continue to rise, with 19.3 million cases expected by 2025. The development and investigation of new diagnostic modalities and innovative therapeutic tools is critical for reducing the global cancer burden...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28874415/cytokine-mediated-regulation-of-human-lymphocyte-development-and-function-insights-from-primary-immunodeficiencies
#7
REVIEW
Stuart G Tangye, Simon J Pelham, Elissa K Deenick, Cindy S Ma
Cytokine-mediated intracellular signaling pathways are fundamental for the development, activation, and differentiation of lymphocytes. These distinct processes underlie protection against infectious diseases after natural infection with pathogens or immunization, thereby providing the host with long-lived immunological memory. In contrast, aberrant cytokine signaling can also result in conditions of immune dysregulation, such as early-onset autoimmunity. Thus, balanced signals provided by distinct cytokines, and delivered to specific cell subsets, are critical for immune homeostasis...
September 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28859112/mathematical-modelling-as-a-proof-of-concept-for-mpns-as-a-human-inflammation-model-for-cancer-development
#8
Morten Andersen, Zamra Sajid, Rasmus K Pedersen, Johanne Gudmand-Hoeyer, Christina Ellervik, Vibe Skov, Lasse Kjær, Niels Pallisgaard, Torben A Kruse, Mads Thomassen, Jesper Troelsen, Hans Carl Hasselbalch, Johnny T Ottesen
The chronic Philadelphia-negative myeloproliferative neoplasms (MPNs) are acquired stem cell neoplasms which ultimately may transform to acute myelogenous leukemia. Most recently, chronic inflammation has been described as an important factor for the development and progression of MPNs in the biological continuum from early cancer stage to the advanced myelofibrosis stage, the MPNs being described as "A Human Inflammation Model for Cancer Development". This novel concept has been built upon clinical, experimental, genomic, immunological and not least epidemiological studies...
2017: PloS One
https://www.readbyqxmd.com/read/28838391/programmed-death-ligand-1-expression-and-t790m-status-in-egfr-mutant-non-small-cell-lung-cancer
#9
Akito Hata, Nobuyuki Katakami, Shigeki Nanjo, Chiyuki Okuda, Reiko Kaji, Katsuhiro Masago, Shiro Fujita, Hiroshi Yoshida, Kota Zama, Yukihiro Imai, Yukio Hirata
BACKGROUND: Differential biology and prognosis between T790M+ and T790M- populations imply immunological differences also. METHODS: We retrospectively analyzed programmed death-ligand 1 (PD-L1) expression and T790M status in rebiopsied samples of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). PD-L1 immunohistochemistry was performed using the SP142 antibody for tumour cell (TC) and tumour-infiltrating immune cell (IC) and the 28-8 antibody for TC...
September 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28805806/lung-tumor-exome-files-with-t-cell-receptor-recombinations-a-mouse-model-of-t-cell-infiltrates-reflecting-mutation-burdens
#10
Yaping N Tu, Wei Lue Tong, Timothy J Fawcett, George Blanck
Tumor exomes and RNASeq data were originally intended for obtaining tumor mutations and gene expression profiles, respectively. However, recent work has determined that tumor exome and RNAseq read files contain reads representing T-cell and B-cell receptor (TcR and BcR) recombinations, presumably due to infiltrating lymphocytes. Furthermore, the recovery of immune receptor recombination reads has demonstrated correlations with specific, previously appreciated aspects of tumor immunology. To further understand the usefulness of recovering TcR and BcR recombinations from tumor exome files, we developed a scripted algorithm for recovery of reads representing these recombinations from a previously described mouse model of lung tumorigenesis...
August 14, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28747311/an-n-terminal-pfs230-domain-produced-in-baculovirus-as-a-biological-active-transmission-blocking-vaccine-candidate
#11
Shwu-Maan Lee, Chia-Kuei Wu, Jordan L Plieskatt, Kazutoyo Miura, John M Hickey, C Richter King
Transmission-blocking vaccines have the potential to accelerate malaria parasite elimination by inducing antibodies that block parasite transmission from humans to mosquitoes. Pfs230, a gametocyte surface protein involved in gamete function, has long been a promising candidate. Due to the large size (3,135 amino acids), complex domains, and repeating six-cysteine (6-Cys) motifs with a multitude of disulfide bonds, the feasibility of expression of a full-length protein has been difficult. A priority focus, therefore, has been on the generation of single domains, including N-terminal fragments...
July 26, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28678791/modeling-the-receptor-pharmacology-pharmacokinetics-and-pharmacodynamics-of-nktr-214-a-kinetically-controlled-interleukin-2-il2-receptor-agonist-for-cancer-immunotherapy
#12
Deborah Charych, Samira Khalili, Vidula Dixit, Peter Kirk, Thomas Chang, John Langowski, Werner Rubas, Stephen K Doberstein, Michael Eldon, Ute Hoch, Jonathan Zalevsky
Cytokines are potent immune modulating agents but are not ideal medicines in their natural form due to their short half-life and pleiotropic systemic effects. NKTR-214 is a clinical-stage biologic that comprises interleukin-2 (IL2) protein bound by multiple releasable polyethylene glycol (PEG) chains. In this highly PEG-bound form, the IL2 is inactive; therefore, NKTR-214 is a biologic prodrug. When administered in vivo, the PEG chains slowly release, creating a cascade of increasingly active IL2 protein conjugates bound by fewer PEG chains...
2017: PloS One
https://www.readbyqxmd.com/read/28652580/immunological-phenotype-of-the-murine-lrba-knockout
#13
Laura Gámez-Díaz, Julika Neumann, Fiona Jäger, Michele Proietti, Felicitas Felber, Pauline Soulas-Sprauel, Lisa Perruzza, Fabio Grassi, Tamara Kögl, Peter Aichele, Manfred Kilimann, Bodo Grimbacher, Sophie Jung
Biallelic mutations in the human lipopolysaccharide responsive beige-like anchor (LRBA) gene lead to a primary immunodeficiency known as LRBA deficiency, characterized by a broad range of clinical manifestations including autoimmunity, organomegaly, hypogammaglobulinemia and recurrent infections. Considering the phenotypic heterogeneity in patients and the severity of the disease, our aim was to assess the role of LRBA in immune cells and to understand the underlying pathomechanisms through the study of a Lrba knockout (Lrba(-/-)) mouse model...
October 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28641617/-biological-characteristics-and-therapeutic-efficacy-of-103-patients-with-acute-erythroleukemia
#14
Yue Yin, Wen-Qi Zhan, Hui-Fang Huang, Chen-Qing Zhang, Dang-Hui Fu, Shu-Juan Xu, Jian-Da Hu, Xin-Ji Chen
OBJECTIVE: To investigate the biological characteristics and therapeutic efficacyt of acute erythroleukemia (AEL,AML-M6). METHODS: Blood cell count, liver function, lactate dehydrogenase level, coagulation, morphology, immunology, cell genetics and molecular biology were retrospectively analyzed in 103 cases of acute erythroleukemia patients admitted in our department from May 2016 to June 2009. The therapeutic efficacy was observed by means of remission rate, relapse rate, relapse-free survival and overall survival...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28611475/murine-lrba-deficiency-causes-ctla-4-deficiency-in-tregs-without-progression-to-immune-dysregulation
#15
Deborah L Burnett, Ian A Parish, Etienne Masle-Farquhar, Robert Brink, Christopher C Goodnow
Inherited mutations in lipopolysaccharide-responsive beige-like anchor (LRBA) cause a recessive human immune dysregulation syndrome with memory B-cell and antibody deficiency (common variable immunodeficiency), inflammatory bowel disease, enlarged spleen and lymph nodes, accumulation of activated T cells and multiple autoimmune diseases. To understand the pathogenesis of the syndrome, C57BL/6 mice carrying a homozygous truncating mutation in Lrba were produced using CRISPR/Cas9-mediated gene targeting. These mice revealed that LRBA has a critical, cell-autonomous role in promoting cytotoxic T-lymphocyte antigen-4 (CTLA-4) accumulation within CD4 effector T cells and FOXP3(+) T-regulatory cells (Tregs)...
October 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28579171/the-ndr-lats-protein-kinases-in-immunology-and-cancer-biology
#16
REVIEW
Ahmad A D Sharif, Alexander Hergovich
The NDR (nuclear Dbf2-related)/LATS (large tumour suppressor) family of kinases represents a subclass of the AGC (protein kinase A (PKA)/PKG/PKC-like) group of serine/threonine protein kinases. Members of the NDR/LATS family are vital components of conserved pathways controlling essential cellular processes, such as proliferation (cell cycle progression) and cell death. In particular, the central involvement of NDR/LATS as YAP/TAZ kinases in the Hippo tissue growth control pathway has gained much interest. In this review, we summarize the roles of mammalian NDR1/2 (aka STK38/STK38L) and LATS1/2 in immunity and cancer biology...
June 1, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28544818/ubiquitination-in-melanoma-pathogenesis-and-treatment
#17
REVIEW
Jinyuan Ma, Weinan Guo, Chunying Li
Melanoma is one of the most aggressive skin cancers with fiercely increasing incidence and mortality. Since the progressive understanding of the mutational landscape and immunologic pathogenic factors in melanoma, the targeted therapy and immunotherapy have been recently established and gained unprecedented improvements for melanoma treatment. However, the prognosis of melanoma patients remains unoptimistic mainly due to the resistance and nonresponse to current available drugs. Ubiquitination is a posttranslational modification which plays crucial roles in diverse cellular biological activities and participates in the pathogenesis of various cancers, including melanoma...
June 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28405017/lectin-pathway-factors-in-patients-suffering-from-juvenile-idiopathic-arthritis
#18
Katarzyna Kasperkiewicz, Łukasz Eppa, Anna S Świerzko, Marcin A Bartłomiejczyk, Zbigniew M Żuber, Katarzyna Siniewicz-Luzeńczyk, Elżbieta Mężyk, Misao Matsushita, Leokadia Bąk-Romaniszyn, Krzysztof Zeman, Mikael Skurnik, Maciej Cedzyński
Both complement activation and certain infections (including those with Yersinia sp.) may contribute to the pathogenesis of juvenile idiopathic arthritis (JIA). We investigated factors specific for the lectin pathway of complement: mannose-binding lectin (MBL), ficolins and MBL-associated serine protease-2 (MASP-2), in 144 patients and 98 controls. One hundred and six patients had oligoarticular disease and 38 had polyarticular disease. In 51 patients (out of 133 tested), Yersinia-reactive antibodies were found (JIA Ye(+) group)...
September 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28373404/precancer-atlas-to-drive-precision-prevention-trials
#19
Avrum Spira, Matthew B Yurgelun, Ludmil Alexandrov, Anjana Rao, Rafael Bejar, Kornelia Polyak, Marios Giannakis, Ali Shilatifard, Olivera J Finn, Madhav Dhodapkar, Neil E Kay, Esteban Braggio, Eduardo Vilar, Sarah A Mazzilli, Timothy R Rebbeck, Judy E Garber, Victor E Velculescu, Mary L Disis, Douglas C Wallace, Scott M Lippman
Cancer development is a complex process driven by inherited and acquired molecular and cellular alterations. Prevention is the holy grail of cancer elimination, but making this a reality will take a fundamental rethinking and deep understanding of premalignant biology. In this Perspective, we propose a national concerted effort to create a Precancer Atlas (PCA), integrating multi-omics and immunity - basic tenets of the neoplastic process. The biology of neoplasia caused by germline mutations has led to paradigm-changing precision prevention efforts, including: tumor testing for mismatch repair (MMR) deficiency in Lynch syndrome establishing a new paradigm, combinatorial chemoprevention efficacy in familial adenomatous polyposis (FAP), signal of benefit from imaging-based early detection research in high-germline risk for pancreatic neoplasia, elucidating early ontogeny in BRCA1-mutation carriers leading to an international breast cancer prevention trial, and insights into the intricate germline-somatic-immunity interaction landscape...
April 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28303031/a-biologically-validated-hcv-e1e2-heterodimer-structural-model
#20
Matteo Castelli, Nicola Clementi, Jennifer Pfaff, Giuseppe A Sautto, Roberta A Diotti, Roberto Burioni, Benjamin J Doranz, Matteo Dal Peraro, Massimo Clementi, Nicasio Mancini
The design of vaccine strategies and the development of drugs targeting the early stages of Hepatitis C virus (HCV) infection are hampered by the lack of structural information about its surface glycoproteins E1 and E2, the two constituents of HCV entry machinery. Despite the recent crystal resolution of limited versions of both proteins in truncated form, a complete picture of the E1E2 complex is still missing. Here we combined deep computational analysis of E1E2 secondary, tertiary and quaternary structure with functional and immunological mutational analysis across E1E2 in order to propose an in silico model for the ectodomain of the E1E2 heterodimer...
March 16, 2017: Scientific Reports
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