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Immunology, mutations, biology

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https://www.readbyqxmd.com/read/29676014/autoinflammatory-disease-in-the-lung
#1
REVIEW
Thomas Scambler, Jonathan Holbrook, Sinisa Savic, Michael F McDermott, Daniel Peckham
Ascertaining the dominant cell type driving an immunological disease is essential to understanding the causal pathology and, therefore, selecting or developing an effective treatment. Classifying immunological diseases in this way has led to successful treatment regimens for many monogenic diseases; however, when the dominant cell type is unclear and there is no obvious causal genetic mutation, then identifying the correct disease classification and appropriate therapy can be challenging. In this review we focus on pulmonary immunological diseases where an innate immune signature has been identified as a predominant aspect of the immunopathology...
April 19, 2018: Immunology
https://www.readbyqxmd.com/read/29666117/novel-insights-into-the-pathogenesis-of-t-cell-lymphomas
#2
John S Van Arnam, Megan S Lim, Kojo S J Elenitoba-Johnson
T-cell lymphomas are a heterogeneous group of rare malignancies with overlapping clinical, immunologic and histologic features. Recent advances in our understanding of T-cell differentiation based on gene expression profiling, next-generation sequencing (NGS) and transgenic mouse modeling studies have better elucidated the pathogenetic mechanisms underlying the diverse biology of T-cell lymphomas. These studies show that while genetic alterations in epigenetic modifiers are implicated in all subtypes of T-cell lymphomas, specific subtypes demonstrate enrichment for particular recurrent alterations targeting specific genes...
April 17, 2018: Blood
https://www.readbyqxmd.com/read/29606053/high-grade-meningiomas-biology-and-implications
#3
Wenya Linda Bi, Vikram C Prabhu, Ian F Dunn
The epochal developments in the treatment of meningioma-microsurgery, skull base techniques, and radiation therapy-will be appended to include the rational application of targeted and immune therapeutics, previously ill-fitting concepts for a tumor that has traditionally been a regarded as a surgical disease. The genomic and immunological architecture of these tumors continues to be defined in ever-greater detail. Grade I meningiomas are driven by NF2 alterations or mutations in AKT1, SMO, TRAF7, PIK3CA, KLF4, POLR2A, SUFU, and SMARCB1...
April 2018: Neurosurgical Focus
https://www.readbyqxmd.com/read/29534030/any-place-for-immunohistochemistry-within-the-predictive-biomarkers-of-treatment-in-lung-cancer-patients
#4
REVIEW
Véronique Hofman, Sandra Lassalle, Coraline Bence, Elodie Long-Mira, Sacha Nahon-Estève, Simon Heeke, Virginie Lespinet-Fabre, Catherine Butori, Marius Ilié, Paul Hofman
The identification of certain genomic alterations ( EGFR , ALK , ROS1 , BRAF ) or immunological markers (PD-L1) in tissues or cells has led to targeted treatment for patients presenting with late stage or metastatic lung cancer. These biomarkers can be detected by immunohistochemistry (IHC) and/or by molecular biology (MB) techniques. These approaches are often complementary but depending on, the quantity and quality of the biological material, the urgency to get the results, the access to technological platforms, the financial resources and the expertise of the team, the choice of the approach can be questioned...
March 13, 2018: Cancers
https://www.readbyqxmd.com/read/29406361/precision-medicine-in-the-treatment-of-primary-immunodeficiency-diseases
#5
Jennifer W Leiding, Mark Ballow
PURPOSE OF THE REVIEW: Since the 1990s with the advances in molecular biology, a number of genetic defects have been described. The International Union of Immunological Sciences has recently updated the classification of genetic defects associated with primary immune deficiencies that now number 354. With the ever-expanding list of new monogenic disorders and a better understanding of the immunobiology and function of these defective genes, new therapies have emerged particularly aimed at the autoimmune and inflammatory conditions that plague these patients...
April 2018: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29387965/cell-biology-of-glioblastoma-multiforme-from-basic-science-to-diagnosis-and-treatment
#6
George S Stoyanov, Deyan Dzhenkov, Peter Ghenev, Bogomil Iliev, Yavor Enchev, Anton B Tonchev
First described in the 1800s, glioblastoma multiforme (GBM), a class IV neoplasm with astrocytic differentiation, as per the revised 2016 World Health Organization classification of tumors of the central nervous system (CNS) is the most common malignant tumor of the CNS. GBM has an extremely wide set of alterations, both genetic and epigenetic, which yield a great number of mutation subgroups, some of which have an established role in independent patient survival and treatment response. All of those components not only represent a closed cycle but are also relevant to the tumor biological behavior and resistance to treatment as they form the pathobiological behavior and clinical course...
January 31, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29363668/leptin-receptor-q223r-polymorphism-influences-neutrophil-mobilization-after-clostridium-difficile-infection
#7
S Jose, M M Abhyankar, A Mukherjee, J Xue, H Andersen, D B Haslam, R Madan
Clostridium difficile is the leading cause of nosocomial infections in the United States. Clinical disease outcomes after C. difficile infection (CDI) are dependent on intensity of host inflammatory responses. Specifically, peak peripheral white blood cell (WBC) count >20 × 109  l-1 is an indicator of adverse outcomes in CDI patients, and is associated with higher 30-day mortality. We show that homozygosity for a common single nucleotide polymorphism (Q to R mutation in leptin receptor that is present in up to 50% of people), significantly increases the risk of having peak peripheral WBC count >20 × 109  l-1 (odds ratio=5...
January 24, 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/29342862/heterogeneous-contributing-factors-in-mpm-disease-development-and-progression-biological-advances-and-clinical-implications
#8
REVIEW
Bhairavi Tolani, Luis A Acevedo, Ngoc T Hoang, Biao He
Malignant pleural mesothelioma (MPM) tumors are remarkably aggressive and most patients only survive for 5-12 months; irrespective of stage; after primary symptoms appear. Compounding matters is that MPM remains unresponsive to conventional standards of care; including radiation and chemotherapy. Currently; instead of relying on molecular signatures and histological typing; MPM treatment options are guided by clinical stage and patient characteristics because the mechanism of carcinogenesis has not been fully elucidated; although about 80% of cases can be linked to asbestos exposure...
January 13, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29237129/zap-70-in-signaling-biology-and-disease
#9
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
#10
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
#11
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
#12
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...
January 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29081765/breast-cancer-vaccines-new-insights
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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...
December 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
#19
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
#20
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
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