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https://www.readbyqxmd.com/read/28741506/sasp-tumor-suppressor-or-promoter-yes
#1
REVIEW
Sonia G Rao, James G Jackson
Cellular senescence is a permanent growth arrest in cells with damage or stress that could lead to transformation. Some tumor cells also undergo senescence in response to chemotherapy. Senescent cells secrete cytokines and other factors of the senescence-associated secretory phenotype (SASP) that contribute to tumor suppression by enforcing arrest and recruiting immune cells that remove these damaged or oncogene-expressing cells from organisms. However, some cells can develop a SASP comprising factors that are immunosuppressive and protumorigenic by paracrine mechanisms...
November 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28726780/foxq1-regulates-senescence-associated-inflammation-via-activation-of-sirt1-expression
#2
Pan Wang, Cuicui Lv, Tao Zhang, Junling Liu, Jin Yang, Fangxia Guan, Tianpei Hong
Cellular senescence is an initial barrier to tumor development that prevents the proliferation of premalignant cells. However, some of the features of senescent cells seem to promote tumor progression via senescence-associated secretory phenotype (SASP). Here, we demonstrated that the protein level of forkhead box Q1 (FOXQ1), which highly overexpresses in several kinds of tumors, was significantly downregulated during both replicative and oncogene-induced senescence. Moreover, overexpression of FOXQ1 delayed senescence, whereas FOXQ1 silence led to premature senescence in human fibroblasts...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28716705/pathobiology-of-biliary-epithelia
#3
REVIEW
Angela C Cheung, Maria J Lorenzo Pisarello, Nicholas F LaRusso
Cholangiocytes are epithelial cells that line the intra- and extrahepatic biliary tree. They serve predominantly to mediate the content of luminal biliary fluid, which is controlled via numerous signaling pathways influenced by endogenous (e.g., bile acids, nucleotides, hormones, neurotransmitters etc.) and exogenous (microbes/microbial products, drugs etc.) molecules. When injured, cholangiocytes undergo apoptosis/lysis, repair and proliferation. They also become senescent, a form of cell cycle arrest, which may prevent propagation of injury and/or malignant transformation...
July 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28711031/the-sinomenine-enteric-coated-microspheres-suppressed-the-tlr-nf-%C3%AE%C2%BAb-signaling-in-dss-induced-experimental-colitis
#4
Huifang Xiong, Liang Tian, Zihan Zhao, Shuping Chen, Qiaoyun Zhao, Junbo Hong, Yong Xie, Nanjin Zhou, Yingjun Fu
Sinomenine is a pure alkaloid with immunosuppressive effects that is extracted from the Chinese medicinal plant Sinomenium acutum. We studied the therapeutic effects of sinomenine on inflammatory bowel disease. In this study, we randomly divided mice into the following ten groups: Control group; DSS-induced colitis group; Salicylazosulfapyridine (SASP)-treated group; Chitosan-treated group; low-, medium-, and high-dose sinomenine-treated and sinomenine enteric-coated microspheres-treated groups. We recorded changes in colon length, disease activity index (DAI), and colon pathology, measured TLR4, MyD88, SIGIRR, NF-κB p65 protein levels and inflammatory serum cytokine levels...
July 12, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28701312/inflammation-and-premature-aging-in-advanced-chronic-kidney-disease
#5
Jeroen Kooman, Marijke Dekker, Len A Usvyat, Peter Kotanko, Frank Van der Sande, Casper G Schalkwijk, Paul G Shiels, Peter Stenvinkel
Systemic inflammation in end-stage renal disease (ESRD) is an established risk factor for mortality and a catalyst for other complications which are related to a premature aging phenotype, including muscle wasting, vascular calcification and other forms of premature vascular disease, depression, osteoporosis and frailty. Uremic inflammation is also mechanistically related to mechanisms involved in the aging process, such as telomere shortening, mitochondrial dysfunction, and altered nutrient sensing, which can have direct effect on cellular and tissue function...
July 12, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28700735/molecular-mechanisms-by-which-casein-glycomacropeptide-maintains-internal-homeostasis-in-mice-with-experimental-ulcerative-colitis
#6
Yongbo Cui, Chenchen Zhu, Zhu Ming, Jiangming Cao, Yali Yan, Pei Zhao, Guangchang Pang, Zixin Deng, Yi Yao, Qingsen Chen
OBJECTIVES: The aim of this study was to elucidate the molecular mechanisms by which food-derived casein glycomacropeptide (CGMP) maintains internal homeostasis in the intestinal mucosa and to investigate the effects of CGMP on the intestinal mucosal immunological barrier and related signal transduction pathways. METHODS: In this study, a famoxadone (OXZ)-induced mouse experimental ulcerative colitis (UC) model was built. The experimental UC mice were intragastrically administered milk-derived CGMP for four consecutive days...
2017: PloS One
https://www.readbyqxmd.com/read/28699239/analysis-of-individual-cells-identifies-cell-to-cell-variability-following-induction-of-cellular-senescence
#7
Christopher D Wiley, James M Flynn, Christapher Morrissey, Ronald Lebofsky, Joe Shuga, Xiao Dong, Marc A Unger, Jan Vijg, Simon Melov, Judith Campisi
Senescent cells play important roles in both physiological and pathological processes, including cancer and aging. In all cases, however, senescent cells comprise only a small fraction of tissues. Senescent phenotypes have been studied largely in relatively homogeneous populations of cultured cells. In vivo, senescent cells are generally identified by a small number of markers, but whether and how these markers vary among individual cells is unknown. We therefore utilized a combination of single-cell isolation and a nanofluidic PCR platform to determine the contributions of individual cells to the overall gene expression profile of senescent human fibroblast populations...
July 11, 2017: Aging Cell
https://www.readbyqxmd.com/read/28673354/the-footprint-of-the-ageing-stroma-in-older-patients-with-breast-cancer
#8
Barbara Brouwers, Debora Fumagalli, Sylvain Brohee, Sigrid Hatse, Olivier Govaere, Giuseppe Floris, Kathleen Van den Eynde, Yacine Bareche, Patrick Schöffski, Ann Smeets, Patrick Neven, Diether Lambrechts, Christos Sotiriou, Hans Wildiers
BACKGROUND: Tumours are not only composed of malignant cells but also consist of a stromal micro-environment, which has been shown to influence cancer cell behaviour. Because the ageing process induces accumulation of senescent cells in the body, this micro-environment is thought to be different in cancers occurring in old patients compared with younger patients. More specifically, senescence-related fibroblastic features, such as the senescence-associated secretory profile (SASP) and the induction of autophagy, are suspected to stimulate tumour growth and progression...
July 3, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28667792/phase-i-study-of-salazosulfapyridine-in-combination-with-cisplatin-and-pemetrexed-for-advanced-non-small-cell-lung-cancer
#9
Kohei Otsubo, Kaname Nosaki, Chiyo K Imamura, Hiroaki Ogata, Akitaka Fujita, Shinya Sakata, Fumihiko Hirai, Gouji Toyokawa, Eiji Iwama, Taishi Harada, Takashi Seto, Mitsuhiro Takenoyama, Takeshi Ozeki, Taisei Mushiroda, Mieko Inada, Junji Kishimoto, Kenji Tsuchihashi, Kentaro Suina, Osamu Nagano, Hideyuki Saya, Yoichi Nakanishi, Isamu Okamoto
Splice variant isoforms of CD44 (CD44v) are a marker of cancer stem cells (CSCs) in solid tumors. They stabilize the xCT subunit of the transporter system xc(-) and thereby promote synthesis of the antioxidant glutathione. Salazosulfapyridine (SASP) is an inhibitor of xCT and suppresses the proliferation of CD44v-positive cancer cells. Chemotherapy-naïve patients with advanced nonsquamous non-small cell lung cancer were enrolled in a dose-escalation study (standard 3 + 3 design) of SASP in combination with cisplatin and pemetrexed...
July 1, 2017: Cancer Science
https://www.readbyqxmd.com/read/28665427/effects-of-bioactive-compounds-on-senescence-and-components-of-senescence-associated-secretory-phenotypes-in-vitro
#10
REVIEW
Janubová Mária, Žitňanová Ingrid
Senescence is a permanent cell cycle arrest that is accompanied by changes in cell morphology and physiology occurring in vitro and in vivo. Senescence evolved as a beneficial response to damage promoting wound healing, limiting fibrosis, fighting against cancer and helping embryonic development. However, excessive accumulation of senescent cells is considered to play a substantial role in the development of aging-related diseases and other morphological and physiological changes associated with aging. Therefore, the aim of many researchers is to find out a way to eliminate senescent cells and improve the health condition of aging people...
July 19, 2017: Food & Function
https://www.readbyqxmd.com/read/28647344/oncogene-expressing-senescent-melanocytes-upregulate-mhc-class-ii-a-candidate-melanoma-suppressor-function
#11
John van Tuyn, Farah Jaber-Hijazi, Douglas MacKenzie, John J Cole, Elizabeth Mann, Jeff S Pawlikowski, Taranjit Singh Rai, David M Nelson, Tony McBryan, Andre Ivanov, Karen Blyth, Hong Wu, Simon Milling, Peter D Adams
On acquisition of an oncogenic mutation, primary human and mouse cells can enter oncogene-induced senescence (OIS). OIS is characterized by a stable proliferation arrest and secretion of pro-inflammatory cytokines and chemokines, the senescence-associated secretory phenotype (SASP). Proliferation arrest and the SASP collaborate to enact tumor suppression, the former by blocking cell proliferation and the latter by recruiting immune cells to clear damaged cells. However, the interactions of OIS cells with the immune system are still poorly defined...
June 21, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28641152/urea-induced-ros-accelerate-senescence-in-endothelial-progenitor-cells
#12
Maria D'Apolito, Anna Laura Colia, Maria Lasalvia, Vito Capozzi, Maria Pia Falcone, Massimo Pettoello-Mantovani, Michael Brownlee, Angela Bruna Maffione, Ida Giardino
BACKGROUND AND AIMS: The pathogenic events responsible for the reduction of endothelial progenitor cell (EPC) number and function seen in patients with chronic renal failure (CRF) are poorly understood. Here we investigate the hypothesis that increased concentrations of urea associated with CRF increase ROS production directly in EPCs, causing abnormalities associated with coronary artery disease risk. METHODS: Human EPCs were isolated from peripheral blood mononuclear cells of healthy donors and cultured in the presence or absence of 20 mmol/L urea...
June 15, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28592031/-the-stimulation-of-human-pulmonary-artery-endothelial-cells-by-cigarette-smoke-extract-contributed-to-cell-senescence-and-induced-human-pulmonary-artery-smooth-cell-migration
#13
L Cai, P C Zhu, Y E Wang, Y T Gao, Q L Ao
Objective: To observe the senescent effect of human pulmonary arterial endothelial cells (HPAEC) stimulated by cigarette smoke extract (CSE) and the effect of secretion of senescent cells on human pulmonary arterial smooth muscles cell (HPASMC) proliferation and migration. Methods: HPAEC was treated with different concentrations of CSE in vitro and cell proliferation was determined by CCK8, senescence cells analyzed by detecting the β-gal activity, and the senescent proteins of cells measured by Western blot...
June 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28591504/-cellular-senescence-as-a-common-denominator-in-age-related-diseases
#14
Luis Ángel Maciel-Barón, Viviana I Pérez, Carmen Torres, Viridiana Y González-Puertos, Mina Konigsberg, Norma Edith López-Diazguerrero
Cellular senescence has been traditionally characterized by cell cycle arrest of pot-mitotic cells as a response to a cellular damage. Now is known that senescent cells secret a diverse array of cytokines, chemokines, growth factors and other that altogether are called senescence associates secretory phenotype (SASP), which might have beneficial or deleterious effects on neighbor cells. This review describes those effects as well as the relationship between the SASP and several age related diseases. We also analyze the direction that recent investigations are turning in order to modulate or avoid the effect of the SASP in those pathologies...
July 2017: Revista Médica del Instituto Mexicano del Seguro Social
https://www.readbyqxmd.com/read/28536322/-the-role-of-sasp-in-tumor-microenvironment
#15
Naoko Ohtani
Cellular senescence is a state of irreversible cell proliferation arrest provoked by a persistent DNA damage induced by a variety of potentially oncogenic signals, and it functions as a primary tumor-suppression mechanism. Recent studies, however, revealed that senescent cells have the potential to secrete numerous inflammatory cytokines, chemokines, growth factors and matrix-remodeling factors, since unlike apoptotic cells, senescent cells are viable for a long period of time. This newly identified phenotype of cellular senescence, called senescence-associated secretory phenotype(SASP or senescence-associated secretome), could potentially provide beneficial effects, such as tissue repair, but sometimes could induce deleterious side effects, such as cancer progression, depending on the biological context...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28533436/metformin-synergizes-with-bcl-xl-bcl-2-inhibitor-abt-263-to-induce-apoptosis-specifically-in-p53-defective-cancer-cells
#16
Xinzhe Li, Bo Li, Zhenhong Ni, Peng Zhou, Bin Wang, Jintao He, Haojun Xiong, Fan Yang, Yaran Wu, Xilin Lyu, Yan Zhang, Yijun Zeng, Jiqin Lian, Fengtian He
p53 deficiency, a frequent event in multiple kinds of malignancies, decreases the sensitivity of diverse targeted chemotherapeutics including the BCL-XL/BCL-2 inhibitor ABT-263. Loss of p53 function can activate mTOR complex 1 (mTORC1), which may make it a vulnerable target. Metformin has shown anti-neoplastic efficiency partially through suppressing mTORC1. However, it remains unknown whether mTORC1 activation confers ABT-263 resistance and whether metformin can overcome it in the p53-defective contexts. In this study, we for the first time demonstrated that metformin and ABT-263 synergistically elicited remarkable apoptosis through orchestrating the pro-apoptotic machineries in various p53-defective cancer cells...
May 22, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28533362/cgas-is-essential-for-cellular-senescence
#17
Hui Yang, Hanze Wang, Junyao Ren, Qi Chen, Zhijian J Chen
Cellular senescence is a natural barrier to tumorigenesis and it contributes to the antitumor effects of several therapies, including radiation and chemotherapeutic drugs. Senescence also plays an important role in aging, fibrosis, and tissue repair. The DNA damage response is a key event leading to senescence, which is characterized by the senescence-associated secretory phenotype (SASP) that includes expression of inflammatory cytokines. Here we show that cGMP-AMP (cGAMP) synthase (cGAS), a cytosolic DNA sensor that activates innate immunity, is essential for senescence...
June 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28518126/techniques-to-induce-and-quantify-cellular-senescence
#18
Nicole Noren Hooten, Michele K Evans
In response to cellular stress or damage, proliferating cells can induce a specific program that initiates a state of long-term cell-cycle arrest, termed cellular senescence. Accumulation of senescent cells occurs with organismal aging and through continual culturing in vitro. Senescent cells influence many biological processes, including embryonic development, tissue repair and regeneration, tumor suppression, and aging. Hallmarks of senescent cells include, but are not limited to, increased senescence-associated β-galactosidase activity (SA-β-gal); p16(INK4A), p53, and p21 levels; higher levels of DNA damage, including γ-H2AX; the formation of Senescence-associated Heterochromatin Foci (SAHF); and the acquisition of a Senescence-associated Secretory Phenotype (SASP), a phenomenon characterized by the secretion of a number of pro-inflammatory cytokines and signaling molecules...
May 1, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28502821/sasp-regulation-by-noncoding-rna
#19
REVIEW
Amaresh C Panda, Kotb Abdelmohsen, Myriam Gorospe
Noncoding RNAs (ncRNAs), including micro (mi)RNAs, long noncoding (lnc)RNAs, and circular (circ)RNAs, control specific gene expression programs by regulating transcriptional, post-transcriptional, and post-translational processes. Through their broad influence on protein expression and function, ncRNAs have been implicated in virtually all cellular processes such as proliferation, senescence, quiescence, differentiation, apoptosis, and the stress and immune responses. Senescence is a cellular phenotype associated with the physiologic decline of aging and with age-related pathologies...
May 11, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28489601/cellular-senescence-senescence-associated-secretory-phenotype-and-chronic-kidney-disease
#20
REVIEW
Wen-Juan Wang, Guang-Yan Cai, Xiang-Mei Chen
Chronic kidney disease (CKD) is increasingly being accepted as a type of renal ageing. The kidney undergoes age-related alterations in both structure and function. To date, a comprehensive analysis of cellular senescence and senescence-associated secretory phenotype (SASP) in CKD is lacking. Hence, this review mainly discusses the relationship between the two phenomena to show the striking similarities between SASP and CKD-associated secretory phenotype (CASP). It has been reported that replicative senescence, stress-induced premature ageing, and epigenetic abnormalities participate in the occurrence and development of CKD...
April 21, 2017: Oncotarget
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