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Genetics and immune therapy

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https://www.readbyqxmd.com/read/27922620/relevance-of-necroptosis-in-cancer
#1
REVIEW
Najoua Lalaoui, Gabriela Brumatti
Resistance to caspase-dependent apoptosis is often responsible for treatment failures in cancer. Finding novel therapeutic strategies that can activate alternative cell death programs appears to be appealing. Necroptosis is a form of programmed necrosis that occurs under caspase deficient conditions. This alternative form of cell death has recently emerged as a potential anti-cancer therapy that could overcome apoptosis resistance. A growing understanding of the molecular events triggering necroptosis helped to examine its implication in cancer development and to define new therapeutic strategies...
December 6, 2016: Immunology and Cell Biology
https://www.readbyqxmd.com/read/27917371/hijacker-of-the-antitumor-immune-response-autophagy-is-showing-its-worst-facet
#2
REVIEW
Elodie Viry, Muhammad Zaeem Noman, Tsolère Arakelian, Audrey Lequeux, Salem Chouaib, Guy Berchem, Etienne Moussay, Jérôme Paggetti, Bassam Janji
Macroautophagy (hereafter referred to as autophagy) is a housekeeping process constitutively executed at basal level in all cells to promote cellular homeostasis by regulating organelle and protein turnover. However, autophagy deregulation caused by several stress factors, such as hypoxia, is prevalent in many cancers. It is now well established that autophagy can act as tumor suppressor or tumor promoter depending on tumor type, stage, and genetic context. In developed tumors, autophagy promotes the survival of cancer cells and therefore operates as a cell resistance mechanism...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27916611/cytokine-signatures-in-hereditary-fever-syndromes-hfs
#3
REVIEW
José Noel Ibrahim, Isabelle Jéru, Jean-Claude Lecron, Myrna Medlej-Hashim
Hereditary fever syndromes (HFS) include a group of disorders characterized by recurrent self-limited episodes of fever accompanied by inflammatory manifestations occurring in the absence of infection or autoimmune reaction. Advances in the genetics of HFS have led to the identification of new gene families and pathways involved in the regulation of inflammation and innate immunity. The key role of several cytokine networks in the pathogenesis of HFS has been underlined by several groups, and supported by the rapid response of patients to targeted cytokine blocking therapies...
November 22, 2016: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/27914655/crohn-s-disease
#4
REVIEW
Joana Torres, Saurabh Mehandru, Jean-Frédéric Colombel, Laurent Peyrin-Biroulet
Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract, with increasing incidence worldwide. Crohn's disease might result from a complex interplay between genetic susceptibility, environmental factors, and altered gut microbiota, leading to dysregulated innate and adaptive immune responses. The typical clinical scenario is a young patient presenting with abdominal pain, chronic diarrhoea, weight loss, and fatigue. Assessment of disease extent and of prognostic factors for complications is paramount to guide therapeutic decisions...
November 30, 2016: Lancet
https://www.readbyqxmd.com/read/27914464/immunogenicity-of-human-interferon-beta-containing-pharmaceuticals
#5
V D Nazarov, S V Lapin, A V Mazing, E P Evdoshenko, A A Totolian
Multiple sclerosis is a severe autoimmune disease with inflammatory component that continues to be resistant to treatment. One of the approaches retarding its progression is based on using nonspecific therapy with human interferon-beta (IFN-β)-containing pharmaceuticals. Neutralizing antibodies (NAbs) against genetically engineered pharmaceuticals developed by the patient's immune system, which reduce their therapeutic and biological activity, pose a serious problem. Cell lines sensitive to IFN-β activity also quantifying NAb level are applied because direct measurement of IFN-β antiviral activity is complicated...
November 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27913524/cellular-and-vaccine-immunotherapy-for-multiple-myeloma
#6
Alfred L Garfall, Edward A Stadtmauer
Allogeneic hematopoietic cell transplantation and donor lymphocyte infusion for multiple myeloma (MM) can induce graft-versus-myeloma immunity and long-term survivorship, but limited efficacy and associated toxicities have prevented its widespread use. Cellular immunotherapies and vaccines seek to induce more specific, reliable, and potent antimyeloma immune responses with less treatment-related risk than is possible with allogeneic transplantation. Advances in molecular biology, and basic and applied immunology, have led to promising approaches such as genetically engineered T cells with chimeric antigen receptors and T-cell receptors targeting myeloma-specific epitopes, vaccine primed ex vivo expanded autologous T cells, expanded marrow-infiltrating lymphocytes, and plasma cell/dendritic cell fusion vaccines...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913459/children-with-rare-diseases-of-neutrophil-granulocytes-from-therapeutic-orphans-to-pioneers-of-individualized-medicine
#7
Christoph Klein
Neutrophil granulocytes are the most abundant immune cells in the blood yet the pathways orchestrating their differentiation and biological function remain incompletely understood. Studying (ultra-) rare patients with monogenetic defects of neutrophil granulocytes may open new horizons to understand basic principles of hematopoiesis and innate immunity. Here, recent insights into genetic factors controlling myelopoiesis and their more general role in biology will be presented in a clinical perspective. Advances in supportive care, first and foremost the use of recombinant human granulocyte-colony stimulating factor, has made a substantial difference for the quality of life and life expectancy of patients with congenital neutropenia (CN)...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27912061/tumor-interferon-signaling-regulates-a-multigenic-resistance-program-to-immune-checkpoint-blockade
#8
Joseph L Benci, Bihui Xu, Yu Qiu, Tony J Wu, Hannah Dada, Christina Twyman-Saint Victor, Lisa Cucolo, David S M Lee, Kristen E Pauken, Alexander C Huang, Tara C Gangadhar, Ravi K Amaravadi, Lynn M Schuchter, Michael D Feldman, Hemant Ishwaran, Robert H Vonderheide, Amit Maity, E John Wherry, Andy J Minn
Therapeutic blocking of the PD1 pathway results in significant tumor responses, but resistance is common. We demonstrate that prolonged interferon signaling orchestrates PDL1-dependent and PDL1-independent resistance to immune checkpoint blockade (ICB) and to combinations such as radiation plus anti-CTLA4. Persistent type II interferon signaling allows tumors to acquire STAT1-related epigenomic changes and augments expression of interferon-stimulated genes and ligands for multiple T cell inhibitory receptors...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27909880/il-9-producing-cells-in-the-development-of-ige-mediated-food-allergy
#9
REVIEW
Dana Shik, Sunil Tomar, Jee-Boong Lee, Chun-Yu Chen, Andrew Smith, Yui-Hsi Wang
Food allergy is a harmful immune reaction driven by uncontrolled type 2 immune responses. Considerable evidence demonstrates the key roles of mast cells, IgE, and TH2 cytokines in mediating food allergy. However, this evidence provides limited insight into why only some, rather than all, food allergic individuals are prone to develop life-threatening anaphylaxis. Clinical observations suggest that patients sensitized to food through the skin early in life may later develop severe food allergies. Aberrant epidermal thymic stromal lymphopoietin and interleukin (IL) 33 production and genetic predisposition can initiate an allergic immune response mediated by dendritic cells and CD4(+)TH2 cells in inflamed skin...
December 1, 2016: Seminars in Immunopathology
https://www.readbyqxmd.com/read/27909515/myocardial-biopsy-in-idiopathic%C3%A2-atrial-fibrillation-and-other-arrhythmias-nosological-diagnosis-clinical-and-morphological-parallels-and-treatment
#10
O V Blagova, A V Nedostup, E A Kogan, V A Sulimov, S A Abugov, A G Kupriyanova, V A Zaydenov, A E Donnikov, E V Zaklyazminskaya, E A Okisheva
BACKGROUND: The nosological nature of "idiopathic" arrhythmias and the effect of etiotropic and pathogenetic treatment are often unknown. METHODS AND RESULTS: 19 patients (42.6±11.3 years, 9 women) with atrial fibrillation (n = 16), supraventricular (n = 10) and ventricular (n = 4) premature beats, supraventricular (n = 2) and ventricular tachycardia (n = 1), left bundle branch block (n= 2), AV block (n = 2) without structural heart changes. Viruses were identified (polymerase chain reaction, PCR) along with measurement of anti-heart antibodies (AHA) and endomyocardial biopsy (EMB)...
June 2016: Journal of Atrial Fibrillation
https://www.readbyqxmd.com/read/27906007/what-happens-to-cardiovascular-system-behind-the-undetectable-level-of-hiv-viremia
#11
REVIEW
Gabriella d'Ettorre, Giancarlo Ceccarelli, Paolo Pavone, Pietro Vittozzi, Gabriella De Girolamo, Ivan Schietroma, Sara Serafino, Noemi Giustini, Vincenzo Vullo
Despite the combined antiretroviral therapy has improved the length and quality of life of HIV infected patients, the survival of these patients is always decreased compared with the general population. This is the consequence of non-infectious illnesses including cardio vascular diseases. In fact large studies have indicated an increased risk of coronary atherosclerotic disease, myocardial infarction even in HIV patients on cART. In HIV infected patients several factors may contribute to the pathogenesis of cardiovascular problems: life-style, metabolic parameters, genetic predisposition, viral factors, immune activation, chronic inflammation and side effects of antiretroviral therapy...
April 27, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27894441/nonclassic-inflammatory-bowel-disease-in-young-infants-immune-dysregulation-polyendocrinopathy-enteropathy-x-linked-syndrome-and-other-disorders
#12
REVIEW
Shanmuganathan Chandrakasan, Suresh Venkateswaran, Subra Kugathasan
This article discusses non-classical forms of inflammatory bowel disease (IBD) mainly occurs in infants and very young children. Defects in every aspect of the immune system, such as neutrophils, T-cell and B-cell lymphocytes, and macrophages are associated with IBD in infants. Also, non lympho-hematopoietic defects with primary defects in enterocytes can also lead to IBD-like manifestations. Clinical vignettes are presented and the genetic origins and possible management strategies are outlined. Early evaluation of these patients is important because identification of underlying immune defects would facilitate the use of better-targeted therapy for the specific genetic defect...
February 2017: Pediatric Clinics of North America
https://www.readbyqxmd.com/read/27894110/significant-role-s-of-cxcl12-and-the-sdf-1-3-a-genetic-variant-in-the-pathogenesis-of-multiple-sclerosis
#13
Mojgan Noroozi Karimabad, Soudeh Khanamani Falahati-Pour, Gholamhossein Hassanshahi
Both cellular and molecular components of the immune system are among the substantial factors involved in the pathogenesis of multiple sclerosis (MS). Accumulating evidence confirms that chemokines, as the main members of the immune system, play key roles in the regulation of immune responses. Immune system genetic parameters are believed to influence the onset of immune system-related diseases. Regarding the significant role of the CXCR4/CXCL12 axis in cell differentiation and survival and homing of hematopoietic progenitors to the bone marrow and regulation of neuronal progenitor cell migration in the central nervous system (CNS), genetic factors can cause an increased expression of CXCL12 and induce a vigorous immune response against CNS antigens in MS patients...
November 29, 2016: Neuroimmunomodulation
https://www.readbyqxmd.com/read/27891086/circuits-regulating-pleasure-and-happiness-mechanisms-of-depression
#14
Anton J M Loonen, Svetlana A Ivanova
According to our model of the regulation of appetitive-searching vs. distress-avoiding behaviors, the motivation to display these essential conducts is regulated by two parallel cortico-striato-thalamo-cortical, re-entry circuits, including the core and the shell parts of the nucleus accumbens, respectively. An entire series of basal ganglia, running from the caudate nucleus on one side, to the centromedial amygdala on the other side, controls the intensity of these reward-seeking and misery-fleeing behaviors by stimulating the activity of the (pre)frontal and limbic cortices...
2016: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/27888910/genetic-and-immune-dysregulation-in-chronic-rhinosinusitis
#15
REVIEW
Ashleigh Halderman, Andrew P Lane
Chronic rhinosinusitis (CRS) is a prevalent condition that is heterogeneous in disease characteristics and multifactorial in cause. Although sinonasal mucosal inflammation in CRS is often either reversible or well-managed medically and surgically, a significant proportion of patients has a refractory form of CRS despite maximal therapy. Two of the several described factors thought to contribute to disease recalcitrance are genetic influences and dysfunction of the host immune system. Current evidence for a genetic basis of CRS is reviewed, as it pertains to putative abnormalities in innate and adaptive immune function...
February 2017: Otolaryngologic Clinics of North America
https://www.readbyqxmd.com/read/27888126/understanding-the-complex-evolution-of-rapidly-mutating-viruses-with-deep-sequencing-beyond-the-analysis-of-viral-diversity
#16
REVIEW
Preston Leung, Auda A Eltahla, Andrew R Lloyd, Rowena A Bull, Fabio Luciani
With the advent of affordable deep sequencing technologies, detection of low frequency variants within genetically diverse viral populations can now be achieved with unprecedented depth and efficiency. The high-resolution data provided by next generation sequencing technologies is currently recognised as the gold standard in estimation of viral diversity. In the analysis of rapidly mutating viruses, longitudinal deep sequencing datasets from viral genomes during individual infection episodes, as well as at the epidemiological level during outbreaks, now allow for more sophisticated analyses such as statistical estimates of the impact of complex mutation patterns on the evolution of the viral populations both within and between hosts...
November 22, 2016: Virus Research
https://www.readbyqxmd.com/read/27888038/evidence-of-bottleneck-effect-on-hepatitis-c-virus-transmission-between-a-couple-under-interferon-based-therapy
#17
Rafael Alves da Silva, Isabel Maria Vicente Guedes de Carvalho, Renata Prandini Adum de Matos, Lilian Hiromi Tomonari Yamasaki, Cíntia Bittar, Paula Rahal, Ana Carolina Gomes Jardim
Issues on the correlation of viral genetic diversity and treatment response to the hepatitis C infection remain uncertain. The bottleneck effect dictates the characteristics of the viral population that will establish the infection in a new host and is related to how the immune system and treatment will be effective against the virus. Here we evaluated the phylogenetic characteristics of quasispecies population and the treatment response pattern of a HCV infected couple. We also analyzed whether the viral population of these patients indicated that they were exposed to the same source for primer infection...
November 22, 2016: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/27883926/application-of-genetically-engineered-salmonella-typhimurium-for-interferon-gamma-induced-therapy-against-melanoma
#18
Wonsuck Yoon, Yoo Chang Park, Jinseok Kim, Yang Seok Chae, Jung Hye Byeon, Sang-Hyun Min, Sungha Park, Young Yoo, Yong Keun Park, Byeong Mo Kim
Salmonella have been experimentally used as anti-cancer agents, because they show selective growth in tumours. In this study, we genetically modified attenuated Salmonella typhimurium to express and secrete interferon-gamma (IFN-γ) as a tumouricidal agent to enhance the therapeutic efficacy of Salmonella. IFN-γ was fused to the N-terminal region (residues 1-160) of SipB (SipB160) for secretion from bacterial cells. Attenuated S. typhimurium expressing recombinant IFN-γ (S. typhimurium (IFN-γ)) invaded the melanoma cells and induced cytotoxicity...
November 21, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27883001/psoriasis
#19
Jacqueline E Greb, Ari M Goldminz, James T Elder, Mark G Lebwohl, Dafna D Gladman, Jashin J Wu, Nehal N Mehta, Andrew Y Finlay, Alice B Gottlieb
Psoriasis is a chronic, immune-mediated disorder with cutaneous and systemic manifestations and substantial negative effects on patient quality of life. Psoriasis has a strong, albeit polygenic, genetic basis. Whereas approximately half of the accountable genetic effect of psoriasis maps to the major histocompatibility complex, >70 other loci have been identified, many of which implicate nuclear factor-κB, interferon signalling and the IL-23-IL-23 receptor axis. Psoriasis pathophysiology is characterized by abnormal keratinocyte proliferation and immune cell infiltration in the dermis and epidermis involving the innate and adaptive immune systems, with important roles for dendritic cells and T cells, among other cells...
November 24, 2016: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/27873555/different-gene-therapy-strategies-a-overview-for-prostate-cancer
#20
Aline Gomes de Souza, Victor Alexandre Felix Bastos, Isaura Beatriz Borges Silva, Karina Marangoni, Vivian Alonso Goulart
Gene therapy emerged as a mighty alternative for conventional treatment of multiple diseases. It has been defined as a product "that mediate their effects by transcription and/or translation of transferred genetic material and/or by integrating into the host genome and that are administered as nucleic acids, viruses, or genetically engineered microorganisms. The products may be used to modify cells in vivo or transferred to cells ex vivo prior to administration to the recipient". The first therapeutic gene therapy human trial was conducted in 1990 by Michael R...
November 15, 2016: Current Gene Therapy
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