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https://www.readbyqxmd.com/read/28202625/gut-microbiota-promotes-obesity-associated-liver-cancer-through-pge2-mediated-suppression-of-antitumor-immunity
#1
Tze Mun Loo, Fumitaka Kamachi, Yoshihiro Watanabe, Shin Yoshimoto, Hiroaki Kanda, Yuriko Arai, Yaeko Nakajima-Takagi, Atsushi Iwama, Tomoaki Koga, Yukihiko Sugimoto, Takayuki Ozawa, Masaru Nakamura, Miho Kumagai, Koichi Watashi, Makoto M Taketo, Tomohiro Aoki, Shuh Narumiya, Masanobu Oshima, Makoto Arita, Eiji Hara, Naoko Ohtani
Obesity increases the risk of cancers, including hepatocellular carcinomas (HCCs). However, the precise molecular mechanisms through which obesity promotes HCC development are still unclear. Recent studies have shown that gut microbiota may influence liver diseases by transferring its metabolites and components. Here, we show that the hepatic translocation of obesity-induced lipoteichoic acid (LTA), a Gram positive gut microbial component, promotes HCC development by creating a tumor-promoting microenvironment...
February 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28197538/cancer-cell-cannibalism-and-the-sasp-ripples-in-the-murky-waters-of-tumor-dormancy
#2
Thomas J Bartosh
Relapse in cancer patients following an apparent cure and a prolonged latency period, known as tumor dormancy, remains an unrelenting clinical crisis. Here, I expand on our recent findings that potentially link cancer cell cannibalism of bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) to the senescence-associated secretory phenotype (SASP) and tumor dormancy.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28185345/the-female-reproduction-and-senescence-nexus
#3
Cielo Mae D Marquez, Joyce A Ibana, Michael C Velarde
Successful pregnancy is regulated by several soluble factors that are differentially expressed throughout gestation. These factors are important to initiate and establish embryo implantation and parturition. Senescent cells, which undergo permanent cell proliferation arrest in response to stress, also produce several secreted factors, referred to as the senescence-associated secretory phenotype (SASP). Here, we review some of the secreted factors found during early and late pregnancy and compare their expression profile with those of the SASP...
February 10, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28167236/rapamycin-and-the-inhibition-of-the-secretory-phenotype
#4
Rong Wang, Bharath Sunchu, Viviana I Perez
Senescent cells contribute to age-related pathology and loss of function, and their selective removal improves physiological function and extends longevity. Cell senescence is a complex process that can be triggered by multiple challenges. Recently it has been observed that the composition of the secretory phenotype or SASP depends on the insult that triggers cell senescence. Rapamycin, an inhibitor of mTOR that increases longevity in several species, inhibits cell senescence in vitro, while silencing the Nrf2 gene induces premature senescence...
February 4, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28166834/downregulation-of-mir-130b-301b-cluster-is-mediated-by-aberrant-promoter-methylation-and-impairs-cellular-senescence-in-prostate-cancer
#5
João Ramalho-Carvalho, Inês Graça, Antonio Gomez, Jorge Oliveira, Rui Henrique, Manel Esteller, Carmen Jerónimo
BACKGROUND: Numerous DNA-damaging cellular stresses, including oncogene activation and DNA-damage response (DDR), may lead to cellular senescence. Previous observations linked microRNA deregulation with altered senescent patterns, prompting us to investigate whether epigenetic repression of microRNAs expression might disrupt senescence in prostate cancer (PCa) cells. METHODS: Differential methylation mapping in prostate tissues was carried using Infinium HumanMethylation450 BeadChip...
February 6, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28165648/the-impact-of-sasp-and-its-potential-as-a-therapeutic-target-for-senescence-associated-diseases
#6
Sugiko Watanabe, Shimpei Kawamoto, Naoko Ohtani, Eiji Hara
'Cellular senescence' is a state in which cells undergo irreversible cell cycle arrest in response to a variety of cellular stresses. Once cells senesce, they are strongly resistant to any mitogens, including oncogenic stimuli. Therefore, cellular senescence has been assumed to be a potent anticancer mechanism. Although irreversible cell-cycle arrest is traditionally considered the major characteristic of senescent cells, recent studies have revealed some additional functions. Most noteworthy is the increased secretion of various secretory proteins, such as inflammatory cytokines, chemokines, growth factors, and matrix metalloproteinases, into the surrounding extracellular fluid...
February 6, 2017: Cancer Science
https://www.readbyqxmd.com/read/28143833/the-senescence-associated-secretory-phenotype-induces-cellular-plasticity-and-tissue-regeneration
#7
Birgit Ritschka, Mekayla Storer, Alba Mas, Florian Heinzmann, Mari Carmen Ortells, Jennifer P Morton, Owen J Sansom, Lars Zender, William M Keyes
Senescence is a form of cell cycle arrest induced by stress such as DNA damage and oncogenes. However, while arrested, senescent cells secrete a variety of proteins collectively known as the senescence-associated secretory phenotype (SASP), which can reinforce the arrest and induce senescence in a paracrine manner. However, the SASP has also been shown to favor embryonic development, wound healing, and even tumor growth, suggesting more complex physiological roles than currently understood. Here we uncover timely new functions of the SASP in promoting a proregenerative response through the induction of cell plasticity and stemness...
January 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28119098/anti-inflammatory-effects-of-brucea-javanica-oil-emulsion-by-suppressing-nf-%C3%AE%C2%BAb-activation-on-dextran-sulfate-sodium-induced-ulcerative-colitis-in-mice
#8
Yan-Feng Huang, Jiang-Tao Zhou, Chang Qu, Yao-Xing Dou, Qiong-Hui Huang, Zhi-Xiu Lin, Yan-Fang Xian, Jian-Hui Xie, You-Liang Xie, Xiao-Ping Lai, Zi-Ren Su
ETHNOPHARMACOLOGICAL RELEVANCE: Brucea javanica is an important traditional medicinal herb used for the treatment of dysentery, malaria, inflammation and cancer in southeast Asia for many years. However, the anti-inflammatory mechanism of Brucea javanica in the treatment of dysentery (also known as ulcerative colitis, UC) has not been fully illuminated. Brucea javanica oil emulsion (BJOE) is the major active and most common application form of Brucea javanica oil (BJO), which has a variety of pharmacological activities...
January 21, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28116118/drug-interaction-between-methotrexate-and-salazosulfapyridine-in-japanese-patients-with-rheumatoid-arthritis
#9
Morihiro Okada, Hiroshi Fujii, Yukio Suga, Satoshi Morito, Masae Okada, Jun Nishigami, Mitsuhiro Kawano, Tsutomu Shimada, Yoshimichi Sai
BACKGROUND: Methotrexate (MTX) and salazosulfapyridine (SASP) are disease-modifying drugs that are commonly used in the treatment of rheumatoid arthritis (RA), and combination therapy with MTX and SASP is recommended for RA patients who show an inadequate response to monotherapy with either drug. This study was designed to examine the interaction between the two drugs from the viewpoint of serum MTX concentration in Japanese RA patients, who were receiving combination therapy with relatively low doses of MTX and SASP...
2017: Journal of Pharmaceutical Health Care and Sciences
https://www.readbyqxmd.com/read/28073341/sijunzi-decoction-attenuates-2-4-6-trinitrobenzene-sulfonic-acid-tnbs-induced-colitis-in-rats-and-ameliorates-tnbs-induced-claudin-2-damage-via-nf-%C3%AE%C2%BAb-pathway-in-caco2-cells
#10
Yue Lu, HanJie Lin, JinWei Zhang, JianAn Wei, Jing Sun, Ling Han
BACKGROUND: SijunziDecoction (SJZD) is a traditional Chinese medicine prescription used to treat the diseases of gastrointestinal tract since ancient times. The objective of this study was to investigate the protective effects of SJZD on TNBS-induced colitis in rats and TNBS-damaged Caco2 cells. METHODS: The rat colitis model was induced by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). SJZD (2.8 5.6, 11.2 g/kg) or salazosulfapyridine (SASP) (0.4 g/kg) was administrated orally in rats for 7 days...
January 10, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28055114/quantitative-analysis-of-cellular-senescence-in-culture-and-in-vivo
#11
Jing Zhao, Heike Fuhrmann-Stroissnigg, Aditi U Gurkar, Rafael R Flores, Akaitz Dorronsoro, Donna B Stolz, Claudette M St Croix, Laura J Niedernhofer, Paul D Robbins
Cellular senescence refers to the irreversible growth arrest of normally dividing cells in response to various types of stress. Cellular senescence is induced by telomere shortening due to repeated cell division, which causes a DNA damage response, as well as genotoxic, oxidative, and inflammatory stress. Strong mitogenic signaling, such as oncogene activation, also drives cells into a senescent state. Senescent cells express a specific subset of genes, termed the senescence-associated secretory phenotype (SASP), including pro-inflammatory factors, growth factors, and matrix metalloproteinases, which together promote non-cell autonomous, secondary senescence...
January 5, 2017: Current Protocols in Cytometry
https://www.readbyqxmd.com/read/28039358/stromal-senescence-by-prolonged-cdk4-6-inhibition-potentiates-tumor-growth
#12
Xiangnan Guan, Kyle M LaPak, Rebecca C Hennessey, Christina Y Yu, Reena Shakya, Jianying Zhang, Christin E Burd
: Senescent cells within the tumor microenvironment (TME) adopt a pro-inflammatory, senescence-associated secretory phenotype (SASP) that promotes cancer initiation, progression and therapeutic resistance. Here, exposure to Palbociclib (PD-0332991), a CDK4/6 inhibitor, induces senescence and a robust SASP in normal fibroblasts. Senescence caused by prolonged CDK4/6 inhibition is DNA damage-independent and associated with Mdm2 downregulation, whereas the SASP elicited by these cells is largely reliant upon NF-kappaB activation...
December 30, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27951455/relationship-of-inflammatory-profile-of-elderly-patients-serum-and-senescence-associated-secretory-phenotype-with-human-breast-cancer-cells-proliferation-role-of-il6-il8-ratio
#13
Bertha Alicia Barajas-Gómez, Oscar Rosas-Carrasco, Sandra Lisbeth Morales-Rosales, Gibrán Pedraza Vázquez, Viridiana Yazmín González-Puertos, Teresa Juárez-Cedillo, Jorge Antonio García-Álvarez, Norma Edith López-Diazguerrero, Pablo Damián-Matsumura, Mina Königsberg, Armando Luna-López
Aging is considered a systemic, chronic and low-grade inflammatory state, called "inflammaging", which has been contemplated as a risk factor for cancer development and progression in the elderly population. Cellular senescence is a multifactorial phenomenon of growth arrest and distorted function, which has been recognized as a contributor to aging. Senescent cells have an altered secretion pattern called Senescent Associated Secretory Phenotype (SASP), that comprise a complex mix of factors including cytokines, growth factors, chemokines and matrix metalloproteinases among others...
December 9, 2016: Cytokine
https://www.readbyqxmd.com/read/27931848/human-peripheral-late-exhausted-memory-b-cells-express-a-senescent-associated-secretory-phenotype-and-preferentially-utilize-metabolic-signaling-pathways
#14
Daniela Frasca, Alain Diaz, Maria Romero, Bonnie B Blomberg
The percentage of late/exhausted memory (LM) B cells increases with age and we show here that this is associated with a lower influenza vaccine response. To identify novel contributors to the phenotypic and functional changes observed in aged B cells, we sorted the major peripheral B cell subsets [naïve, IgM memory, switched memory (swIg) and late/exhausted memory (LM)] and determined their percentages in the peripheral blood as well as their level of immune activation by measuring basal levels of expression of multiple senescence-associated secretory phenotype (SASP) markers, such as pro-inflammatory cytokines (TNF-α/IL-6/IL-8), inflammatory micro-RNAs (miRs, miR-155/16/93), cell cycle regulators (p16(INK4))...
January 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/27927801/physiological-aging-links-among-adipose-tissue-dysfunction-diabetes-and-frailty
#15
REVIEW
Michael B Stout, Jamie N Justice, Barbara J Nicklas, James L Kirkland
Advancing age is associated with progressive declines in physiological function that lead to overt chronic disease, frailty, and eventual mortality. Importantly, age-related physiological changes occur in cellularity, insulin-responsiveness, secretory profiles, and inflammatory status of adipose tissue, leading to adipose tissue dysfunction. Although the mechanisms underlying adipose tissue dysfunction are multifactorial, the consequences result in secretion of proinflammatory cytokines and chemokines, immune cell infiltration, an accumulation of senescent cells, and an increase in senescence-associated secretory phenotype (SASP)...
January 2017: Physiology
https://www.readbyqxmd.com/read/27907906/senescent-fibroblast-derived-chemerin-promotes-squamous-cell-carcinoma-migration
#16
Vida Farsam, Abhijit Basu, Martina Gatzka, Nicolai Treiber, Lars A Schneider, Medhanie A Mulaw, Tanja Lucas, Stefan Kochanek, Reinhard Dummer, Mitchell P Levesque, Meinhard Wlaschek, Karin Scharffetter-Kochanek
Aging is associated with a rising incidence of cutaneous squamous cell carcinoma (cSCC), an aggressive skin cancer with the potential for local invasion and metastasis. Acquisition of a senescence-associated secretory phenotype (SASP) in dermal fibroblasts has been postulated to promote skin cancer progression in elderly individuals. The underlying molecular mechanisms are largely unexplored. We show that Chemerin, a previously unreported SASP factor released from senescent human dermal fibroblasts, promotes cSCC cell migration, a key feature driving tumor progression...
November 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27889642/redox-control-of-senescence-and-age-related-disease
#17
REVIEW
Akshaya Chandrasekaran, Maria Del Pilar Sosa Idelchik, J Andrés Melendez
The signaling networks that drive the aging process, associated functional deterioration, and pathologies has captured the scientific community's attention for decades. While many theories exist to explain the aging process, the production of reactive oxygen species (ROS) provides a signaling link between engagement of cellular senescence and several age-associated pathologies. Cellular senescence has evolved to restrict tumor progression but the accompanying senescence-associated secretory phenotype (SASP) promotes pathogenic pathways...
November 16, 2016: Redox Biology
https://www.readbyqxmd.com/read/27883166/effect-of-low-dose-rapamycin-on-senescence-markers-and-physical-functioning-in-older-adults-with-coronary-artery-disease-results-of-a-pilot-study
#18
M Singh, M D Jensen, A Lerman, S Kushwaha, C S Rihal, B J Gersh, A Behfar, T Tchkonia, R J Thomas, R J Lennon, L R Keenan, A G Moore, J L Kirkland
Rapamycin, an mTOR inhibitor affects senescence through suppression of senescence-associated secretory phenotype (SASP). We studied the safety and feasibility of low-dose rapamycin and its effect on SASP and frailty in elderly undergoing cardiac rehabilitation (CR). 13 patients; 6 (0.5mg), 6 (1.0mg), and 1 patient received 2mg oral rapamycin (serum rapamycin <6ng/ml) daily for 12 weeks. Median age was 73.9±7.5 years and 12 were men. Serum interleukin-6 decreased (2.6 vs 4.4 pg/ml) and MMP-3 (26 vs 23.5 ng/ml) increased...
2016: Journal of Frailty & Aging
https://www.readbyqxmd.com/read/27867017/genomic-amplification-of-fanconi-anemia-complementation-group-a-fanca-in-head-and-neck-squamous-cell-carcinoma-hnscc-cellular-mechanisms-of-radioresistance-and-clinical-relevance
#19
Julia Hess, Kristian Unger, Michael Orth, Ulrike Schötz, Lars Schüttrumpf, Verena Zangen, Igor Gimenez-Aznar, Agata Michna, Ludmila Schneider, Ramona Stamp, Martin Selmansberger, Herbert Braselmann, Ludwig Hieber, Guido A Drexler, Sebastian Kuger, Diana Klein, Verena Jendrossek, Anna A Friedl, Claus Belka, Horst Zitzelsberger, Kirsten Lauber
Radio (chemo) therapy is a crucial treatment modality for head and neck squamous cell carcinoma (HNSCC), but relapse is frequent, and the underlying mechanisms remain largely elusive. Therefore, novel biomarkers are urgently needed. Previously, we identified gains on 16q23-24 to be associated with amplification of the Fanconi anemia A (FancA) gene and to correlate with reduced progression-free survival after radiotherapy. Here, we analyzed the effects of FancA on radiation sensitivity in vitro, characterized the underlying mechanisms, and evaluated their clinical relevance...
February 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27856491/excavating-the-surface-associated-and-secretory-proteome-of-mycobacterium-leprae-for-identifying-vaccines-and-diagnostic-markers-relevant-immunodominant-epitopes
#20
Aarti Rana, Shweta Thakur, Nupur Bhardwaj, Devender Kumar, Yusuf Akhter
For centuries, Mycobacterium leprae, etiological agent of leprosy, has been afflicting mankind regardless of extensive use of live-attenuated vaccines and antibiotics. Surface-associated and secretory proteins (SASPs) are attractive targets against bacteria. We have integrated biological knowledge with computational approaches and present a proteome-wide identification of SASPs. We also performed computational assignment of immunodominant epitopes as coordinates of prospective antigenic candidates in most important class of SASPs, the outer membrane proteins (OMPs)...
December 2016: Pathogens and Disease
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