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cell clonality and senescence

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https://www.readbyqxmd.com/read/29722927/nf-%C3%AE%C2%BAb-signaling-mechanisms-in-htlv-1-induced-adult-t-cell-leukemia-lymphoma
#1
REVIEW
Edward William Harhaj, Chou-Zen Giam
The human T-cell leukemia virus type 1 (HTLV-1) is a complex deltaretrovirus linked to adult T-cell leukemia/lymphoma (ATLL), a fatal CD4+ malignancy in 3-5% of infected individuals. The HTLV-1 Tax regulatory protein plays indispensable roles in regulating viral gene expression and activating cellular signaling pathways that drive the proliferation and clonal expansion of T cells bearing HTLV-1 proviral integrations. Tax is a potent activator of NF-κB, a key signaling pathway that is essential for the survival and proliferation of HTLV-1 infected T cells...
May 3, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29682980/aging-and-senescence-associated-changes-of-mesenchymal-stromal-cells-in-myelodysplastic-syndromes
#2
Domenico Mattiucci, Giulia Maurizi, Pietro Leoni, Antonella Poloni
Hematopoietic stem and progenitor cells reside within the bone marrow (BM) microenvironment. By a well-balanced interplay between self-renewal and differentiation, they ensure a lifelong supply of mature blood cells. Physiologically, multiple different cell types contribute to the regulation of stem and progenitor cells in the BM microenvironment by cell-extrinsic and cell-intrinsic mechanisms. During the last decades, mesenchymal stromal cells (MSCs) have been identified as one of the main cellular components of the BM microenvironment holding an indispensable role for normal hematopoiesis...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29593711/regenerating-immunotolerance-in-multiple-sclerosis-with-autologous-hematopoietic-stem-cell-transplant
#3
REVIEW
Jennifer C Massey, Ian J Sutton, David D F Ma, John J Moore
Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system where evidence implicates an aberrant adaptive immune response in the accrual of neurological disability. The inflammatory phase of the disease responds to immunomodulation to varying degrees of efficacy; however, no therapy has been proven to arrest progression of disability. Recently, more intensive therapies, including immunoablation with autologous hematopoietic stem cell transplantation (AHSCT), have been offered as a treatment option to retard inflammatory disease, prior to patients becoming irreversibly disabled...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29545794/influence-of-inflammation-in-the-process-of-t-lymphocyte-differentiation-proliferative-metabolic-and-oxidative-changes
#4
REVIEW
Marco A Moro-García, Juan C Mayo, Rosa M Sainz, Rebeca Alonso-Arias
T lymphocytes, from their first encounter with their specific antigen as naïve cell until the last stages of their differentiation, in a replicative state of senescence, go through a series of phases. In several of these stages, T lymphocytes are subjected to exponential growth in successive encounters with the same antigen. This entire process occurs throughout the life of a human individual and, earlier, in patients with chronic infections/pathologies through inflammatory mediators, first acutely and later in a chronic form...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29445421/evidence-for-a-pre-malignant-cell-line-in-a-skin-biopsy-from-a-patient-with-nijmegen-breakage-syndrome
#5
Raneem Habib, Heidemarie Neitzel, Aurelie Ernst, John K L Wong, Bozenna Goryluk-Kozakiewicz, Antje Gerlach, Ilja Demuth, Karl Sperling, Krystyna Chrzanowska
Background: Nijmegen breakage syndrome is an autosomal recessive disorder characterized by microcephaly, immunodeficiency, hypersensitivity to X-irradiation, and a high predisposition to cancer. Nibrin, the product of the NBN gene, is part of the MRE11/RAD50 (MRN) complex that is involved in the repair of DNA double strand breaks (DSBs), and plays a critical role in the processing of DSBs in immune gene rearrangements, telomere maintenance, and meiotic recombination. NBS skin fibroblasts grow slowly in culture and enter early into senescence...
2018: Molecular Cytogenetics
https://www.readbyqxmd.com/read/29351238/telomeres-implications-for-cancer-development
#6
REVIEW
Aina Bernal, Laura Tusell
Telomeres facilitate the protection of natural ends of chromosomes from constitutive exposure to the DNA damage response (DDR). This is most likely achieved by a lariat structure that hides the linear telomeric DNA through protein-protein and protein-DNA interactions. The telomere shortening associated with DNA replication in the absence of a compensatory mechanism culminates in unmasked telomeres. Then, the subsequent activation of the DDR will define the fate of cells according to the functionality of cell cycle checkpoints...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29259496/immunosenescence-in-aging-between-immune-cells-depletion-and-cytokines-up-regulation
#7
REVIEW
Maria Teresa Ventura, Marco Casciaro, Sebastiano Gangemi, Rosalba Buquicchio
Background: The immunosenescence is a relatively recent chapter, correlated with the linear extension of the average life began in the nineteenth century and still in progress. The most important feature of immunosenescence is the accumulation in the "immunological space" of memory and effector cells as a result of the stimulation caused by repeated clinical and subclinical infections and by continuous exposure to antigens (inhalant allergens, food, etc.). This state of chronic inflammation that characterizes senescence has a significant impact on survival and fragility...
2017: Clinical and Molecular Allergy: CMA
https://www.readbyqxmd.com/read/29133867/evidence-of-renal-angiomyolipoma-neoplastic-stem-cells-arising-from-renal-epithelial-cells
#8
Ana Filipa Gonçalves, Mojca Adlesic, Simone Brandt, Tomas Hejhal, Sabine Harlander, Lukas Sommer, Olga Shakhova, Peter J Wild, Ian J Frew
Renal angiomyolipomas (AML) contain an admixture of clonal tumour cells with features of several different mesenchymal lineages, implying the existence of an unidentified AML neoplastic stem cell. Biallelic inactivation of TSC2 or TSC1 is believed to represent the driving event in these tumours. Here we show that TSC2 knockdown transforms senescence-resistant cultured mouse and human renal epithelial cells into neoplastic stem cells that serially propagate renal AML-like tumours in mice. mTOR inhibitory therapy of mouse AML allografts mimics the clinical responses of human renal AMLs...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28832180/effect-of-pou5f1-expression-level-in-clonal-subpopulations-of-bovine-fibroblasts-used-as-nuclear-donors-for-somatic-cell-nuclear-transfer
#9
André Luiz Sá, Rafael V Sampaio, Nathália Nogueira da Costa Almeida, Juliano Rodrigues Sangalli, Karynne Nazaré Lins Brito, Fabiana Fernandes Bressan, Joirge Dores Rissino, Simone do Socorro Damasceno Santos, Flavio Vieira Meirelles, Otávio Mitio Ohashi, Moysés Dos Santos Miranda
Somatic cell nuclear transfer (SCNT) success is partially hindered by the low epigenetic reprogramming efficiency of the donor cell. Previous studies suggest cellular heterogeneity among donor nuclei in regard to reprogramming potential, which precludes comparison among different strategies to increase cloning success. In this context, we evaluated the effect of using clonal cell populations (CPs) of bovine adult fibroblasts established by single-cell plating in SCNT. Different CPs were evaluated in regard to proliferation rate, senescence level, and chromosome stability, as well as for POU5F1 (POU class 5 homeobox 1) mRNA expression levels...
October 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28680762/tumor-targeted-il-12-combined-with-local-irradiation-leads-to-systemic-tumor-control-via-abscopal-effects-in-vivo
#10
Franziska Eckert, Ivan Jelas, Moritz Oehme, Stephan M Huber, Katja Sonntag, Christian Welker, Stephen D Gillies, Wolfgang Strittmatter, Daniel Zips, Rupert Handgretinger, Karin Schilbach
NHS-IL12 is an immunocytokine, a fusion protein of IL12's functional domains and a necrosis-targeting antibody, which has shown significant effects against human rhabdomyosarcoma xenografts in a humanized tumor model, including terminal growth arrest and differentiation of the tumor cells. Here, we locally irradiated the tumors, increasing necrosis and consequently intratumoral immune cytokine availability, and asked whether this effect may surmount efficacy of single treatment modality. Humanized mice bearing bilateral rhabdomyosarcoma xenografts were evaluated for tumor burden and survival after irradiation, systemic NHS-IL12 therapy or a combination of both...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28659925/immune-checkpoint-function-of-cd85j-in-cd8-t-cell-differentiation-and-aging
#11
Claire E Gustafson, Qian Qi, Jessica Hutter-Saunders, Sheena Gupta, Rohit Jadhav, Evan Newell, Holden Maecker, Cornelia M Weyand, Jörg J Goronzy
Aging is associated with an increased susceptibility to infection and a failure to control latent viruses thought to be driven, at least in part, by alterations in CD8 T cell function. The aging T cell repertoire is characterized by an accumulation of effector CD8 T cells, many of which express the negative regulatory receptor CD85j. To define the biological significance of CD85j expression on CD8 T cells and to address the question whether presence of CD85j in older individuals is beneficial or detrimental for immune function, we examined the specific attributes of CD8 T cells expressing CD85j as well as the functional role of CD85j in antigen-specific CD8 T cell responses during immune aging...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28588756/immunological-aspects-of-age-related-diseases
#12
REVIEW
Ken-Ichi Isobe, Naomi Nishio, Tadao Hasegawa
The proportion of elderly people rises in the developed countries. The increased susceptibility of the elderly to infectious diseases is caused by immune dysfunction, especially T cell functional decline. Age-related hematopoietic stem cells deviate from lymphoid lineage to myeloid lineage. Thymus shrinks early in life, which is followed by the decline of naïve T cells. T-cell receptor repertoire diversity declines by aging, which is caused by cytomegalovirus-driven T cell clonal expansion. Functional decline of B cell induces antibody affinity declines by aging...
May 26, 2017: World Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28341737/an-abnormal-bone-marrow-microenvironment-contributes-to-hematopoietic-dysfunction-in-fanconi-anemia
#13
Yuan Zhou, Yongzheng He, Wen Xing, Peng Zhang, Hui Shi, Shi Chen, Jun Shi, Jie Bai, Steven D Rhodes, Fengqui Zhang, Jin Yuan, Xianlin Yang, Xiaofan Zhu, Yan Li, Helmut Hanenberg, Mingjiang Xu, Kent A Robertson, Weiping Yuan, Grzegorz Nalepa, Tao Cheng, D Wade Clapp, Feng-Chun Yang
Fanconi anemia is a complex heterogeneous genetic disorder with a high incidence of bone marrow failure, clonal evolution to acute myeloid leukemia and mesenchymal-derived congenital anomalies. Increasing evidence in Fanconi anemia and other genetic disorders points towards an interdependence of skeletal and hematopoietic development, yet the impact of the marrow microenvironment in the pathogenesis of the bone marrow failure in Fanconi anemia remains unclear. Here we demonstrated that mice with double knockout of both Fancc and Fancg genes had decreased bone formation at least partially due to impaired osteoblast differentiation from mesenchymal stem/progenitor cells...
June 2017: Haematologica
https://www.readbyqxmd.com/read/28167050/changing-mutational-and-adaptive-landscapes-and-the-genesis-of-cancer
#14
REVIEW
L Alexander Liggett, James DeGregori
By the time the process of oncogenesis has produced an advanced cancer, tumor cells have undergone extensive evolution. The cellular phenotypes resulting from this evolution have been well studied, and include accelerated growth rates, apoptosis resistance, immortality, invasiveness, and immune evasion. Yet with all of our current knowledge of tumor biology, the details of early oncogenesis have been difficult to observe and understand. Where different oncogenic mutations may work together to enhance the survival of a tumor cell, in isolation they are often pro-apoptotic, pro-differentiative or pro-senescent, and therefore often, somewhat paradoxically, disadvantageous to a cell...
April 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28150695/characterisation-of-a-divergent-progenitor-cell-sub-populations-in-human-osteoarthritic-cartilage-the-role-of-telomere-erosion-and-replicative-senescence
#15
Christopher R Fellows, Rebecca Williams, Iwan R Davies, Kajal Gohil, Duncan M Baird, John Fairclough, Paul Rooney, Charles W Archer, Ilyas M Khan
In recent years it has become increasingly clear that articular cartilage harbours a viable pool of progenitor cells and interest has focussed on their role during development and disease. Analysis of progenitor numbers using fluorescence-activated sorting techniques has resulted in wide-ranging estimates, which may be the result of context-dependent expression of cell surface markers. We have used a colony-forming assay to reliably determine chondroprogenitor numbers in normal and osteoarthritic cartilage where we observed a 2-fold increase in diseased tissue (P  < 0...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28148303/variation-in-human-dental-pulp-stem-cell-ageing-profiles-reflect-contrasting-proliferative-and-regenerative-capabilities
#16
Amr Alraies, Nadia Y A Alaidaroos, Rachel J Waddington, Ryan Moseley, Alastair J Sloan
BACKGROUND: Dental pulp stem cells (DPSCs) are increasingly being recognized as a viable cell source for regenerative medicine. Although significant variations in their ex vivo expansion are well-established, DPSC proliferative heterogeneity remains poorly understood, despite such characteristics influencing their regenerative and therapeutic potential. This study assessed clonal human DPSC regenerative potential and the impact of cellular senescence on these responses, to better understand DPSC functional behaviour...
February 2, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28121388/early-life-infection-but-not-breastfeeding-predicts-adult-blood-telomere-lengths-in-the-philippines
#17
Dan T A Eisenberg, Judith B Borja, M Geoffrey Hayes, Christopher W Kuzawa
OBJECTIVES: Telomeres are repetitive DNA at chromosomes ends that shorten with age due to cellular replication and oxidative stress. As telomeres shorten, this can eventually place limits on cell replication and contribute to senescence. Infections are common during early development and activate cellular immune responses that involve clonal expansion and oxidative stress. As such, a high infectious disease burden might shorten blood telomere length (BTL) and accelerate the pace of immune senescence...
July 8, 2017: American Journal of Human Biology: the Official Journal of the Human Biology Council
https://www.readbyqxmd.com/read/28117106/stress-induced-premature-senescence-of-dermal-papilla-cells-compromises-hair-follicle-epithelial-mesenchymal-interaction
#18
Wen-Yen Huang, Yi-Ching Huang, Kai-Shin Huang, Chih-Chieh Chan, Hsien-Yi Chiu, Ren-Yeu Tsai, Jung-Yi Chan, Sung-Jan Lin
BACKGROUND: Hair follicle is miniorgan constituted by keratinocytes and its distinctive mesenchyme of dermal papilla. Its aging is characterized by organ atrophy and impaired stem cell activation and differentiation. The contribution of dermal papilla to hair follicle aging change is not well understood. OBJECTIVE: This work was aimed at exploring the possible role of premature dermal papilla senescence in the pathogenesis of hair follicle aging. METHODS: Dermal papilla cells were challenged with H2O2 to induce premature senescence and the proliferation, apoptosis, gene expression and protein secretion were characterized...
May 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28076901/nuclear-factor-one-transcription-factors-as-epigenetic-regulators-in-cancer
#19
REVIEW
Mitchell Fane, Lachlan Harris, Aaron G Smith, Michael Piper
Tumour heterogeneity poses a distinct obstacle to therapeutic intervention. While the initiation of tumours across various physiological systems is frequently associated with signature mutations in genes that drive proliferation and bypass senescence, increasing evidence suggests that tumour progression and clonal diversity is driven at an epigenetic level. The tumour microenvironment plays a key role in driving diversity as cells adapt to demands imposed during tumour growth, and is thought to drive certain subpopulations back to a stem cell-like state...
June 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27785870/senescence-associated-dna-methylation-is-stochastically-acquired-in-subpopulations-of-mesenchymal-stem-cells
#20
Julia Franzen, Anne Zirkel, Jonathon Blake, Björn Rath, Vladimir Benes, Argyris Papantonis, Wolfgang Wagner
Replicative senescence has a major impact on function and integrity of cell preparations. This process is reflected by continuous DNA methylation (DNAm) changes at specific CpG dinucleotides in the course of in vitro culture, and such modifications can be used to estimate the state of cellular senescence for quality control of cell preparations. Still, it is unclear how senescence-associated DNAm changes are regulated and whether they occur simultaneously across a cell population. In this study, we analyzed global DNAm profiles of human mesenchymal stem cells (MSCs) and human umbilical vein endothelial cells (HUVECs) to demonstrate that senescence-associated DNAm changes are overall similar in these different cell types...
February 2017: Aging Cell
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