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Senescence

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https://www.readbyqxmd.com/read/28535453/inhibition-of-neddylation-modification-sensitizes-pancreatic-cancer-cells-to-gemcitabine
#1
Hua Li, Weihua Zhou, Lihui Li, Jianfu Wu, Xiaoli Liu, Lili Zhao, Lijun Jia, Yi Sun
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA with a 5-year survival rate less than 3% to 5%. Gemcitabine remains as a standard care for PDAC patients. Although protein neddylation is abnormally activated in many human cancers, whether neddylation dysregulation is involved in PDAC and whether targeting neddylation would sensitize pancreatic cancer cells to gemcitabine remain elusive. Here we report that high expression of neddylation components, NEDD8 and NAE1, are associated with poor survival of PDAC patients...
May 20, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28535128/low-and-high-let-ionizing-radiation-induces-delayed-homologous-recombination-that-persists-for-two-weeks-before-resolving
#2
Christopher P Allen, Hirokazu Hirakawa, Nakako Izumi Nakajima, Sophia Moore, Jingyi Nie, Neelam Sharma, Mayumi Sugiura, Yuko Hoki, Ryoko Araki, Masumi Abe, Ryuichi Okayasu, Akira Fujimori, Jac A Nickoloff
Genome instability is a hallmark of cancer cells and dysregulation or defects in DNA repair pathways cause genome instability and are linked to inherited cancer predisposition syndromes. Ionizing radiation can cause immediate effects such as mutation or cell death, observed within hours or a few days after irradiation. Ionizing radiation also induces delayed effects many cell generations after irradiation. Delayed effects include hypermutation, hyper-homologous recombination, chromosome instability and reduced clonogenic survival (delayed death)...
May 23, 2017: Radiation Research
https://www.readbyqxmd.com/read/28534660/radiation-induced-pulmonary-fibrosis-as-a-model-of-progressive-fibrosis-contributions-of-dna-damage-inflammatory-response-and-cellular-senescence-genes
#3
Tyler A Beach, Carl J Johnston, Angela M Groves, Jacqueline P Williams, Jacob N Finkelstein
Purpose/Aim of Study: Studies of pulmonary fibrosis (PF) have resulted in DNA damage, inflammatory response, and cellular senescence being widely hypothesized to play a role in the progression of the disease. Utilizing these aforementioned terms, genomics databases were interrogated along with the term, "pulmonary fibrosis," to identify genes common among all 4 search terms. Findings were compared to data derived from a model of radiation-induced progressive pulmonary fibrosis (RIPF) to verify that these genes are similarly expressed, supporting the use of radiation as a model for diseases involving PF, such as human idiopathic pulmonary fibrosis (IPF)...
May 23, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28534654/functions-and-substrates-of-plastoglobule-localized-metallopeptidase-pgm48
#4
Nazmul H Bhuiyan, Klaas J van Wijk
Plastoglobules (PGs) in chloroplasts are monolayer lipid-protein particles attached to thylakoids. The size and number of PGs per chloroplast respond dynamically to abiotic environmental stresses and developmental transitions. During senescence, the thylakoid membranes and its constituents are dismantled in controlled fashion. Leaf senescence coincides with a dramatic increase in the size of PGs, which is consistent with a functional role of PG in remobilization of thylakoid membrane components. In a recent publication (1) , we showed that PG-localized metallopeptidase PGM48 promotes natural senescence...
May 23, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28534519/two-forms-of-death-in-ageing-caenorhabditis-elegans
#5
Yuan Zhao, Ann F Gilliat, Matthias Ziehm, Mark Turmaine, Hongyuan Wang, Marina Ezcurra, Chenhao Yang, George Phillips, David McBay, William B Zhang, Linda Partridge, Zachary Pincus, David Gems
Ageing generates senescent pathologies, some of which cause death. Interventions that delay or prevent lethal pathologies will extend lifespan. Here we identify life-limiting pathologies in Caenorhabditis elegans with a necropsy analysis of worms that have died of old age. Our results imply the presence of multiple causes of death. Specifically, we identify two classes of corpse: early deaths with a swollen pharynx (which we call 'P deaths'), and later deaths with an atrophied pharynx (termed 'p deaths'). The effects of interventions on lifespan can be broken down into changes in the frequency and/or timing of either form of death...
May 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28533659/braf-inhibitor-treatment-of-melanoma-causing-colonic-polyps-an-alternative-hypothesis
#6
EDITORIAL
Fergal C Kelleher, Grainne Callaghan, Catriona Gallagher, Hazel O'Sullivan
Colonic polyps may arise from BRAF inhibitor treatment of melanoma, possibly due to paradoxical activation of the mitogen-activated protein (MAP)-kinase pathway. In an alternative evidence based scenario, tubular colonic adenomas with APC gene mutations have also been identified in the context of BRAF inhibitor treatment, in the absence of mutations of MAPK genes. A minority of colorectal cancers develop by an alternative "serrated polyp pathway". This article postulates a novel hypothesis, that the established phenotypic and molecular characteristics of serrated colonic polyps/CRC offer an intriguing insight into the pathobiology of BRAF inhibitor induced colonic polyps...
May 7, 2017: World Journal of Gastroenterology: WJG
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
#7
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
#8
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...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28530706/akt-is-indispensable-for-coordinating-par-4-jnk-cross-talk-in-p21-downmodulation-during-er-stress
#9
R U Rasool, D Nayak, S Chakraborty, M M Faheem, B Rah, P Mahajan, V Gopinath, A Katoch, Z Iqra, S K Yousuf, D Mukherjee, L D Kumar, A Nargotra, A Goswami
The double-edged role of p21 to command survival and apoptosis is emerging. The current investigation highlights ER stress-mediated JNK activation that plausibly triggers cell death by attenuating endogenous p21 level. Here, we demonstrated that ER stress activator 3-AWA diminishes the p21 levels in cancer cells by averting the senescent phenotype to commence G2/M arrest. In essence, the deceleration in p21 level occurs through ER stress/JNK/Caspase-3 axis via activation/induction of proapoptotic Par-4 and inhibition of AKT...
May 22, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28530657/normal-and-cancerous-mammary-stem-cells-evade-interferon-induced-constraint-through-the-mir-199a-lcor-axis
#10
Toni Celià-Terrassa, Daniel D Liu, Abrar Choudhury, Xiang Hang, Yong Wei, Jose Zamalloa, Raymundo Alfaro-Aco, Rumela Chakrabarti, Yi-Zhou Jiang, Bong Ihn Koh, Heath A Smith, Christina DeCoste, Jun-Jing Li, Zhi-Ming Shao, Yibin Kang
Tumour-initiating cells, or cancer stem cells (CSCs), possess stem-cell-like properties observed in normal adult tissue stem cells. Normal and cancerous stem cells may therefore share regulatory mechanisms for maintaining self-renewing capacity and resisting differentiation elicited by cell-intrinsic or microenvironmental cues. Here, we show that miR-199a promotes stem cell properties in mammary stem cells and breast CSCs by directly repressing nuclear receptor corepressor LCOR, which primes interferon (IFN) responses...
May 22, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28530531/the-complexity-of-dek-signaling-in-cancer-progression
#11
Yong Teng, Liwei Lang, Catherine E Jauregui
The DNA binding protein and chromatin structural regulator DEK regulates many cellular processes. These include proliferation, differentiation, apoptosis, senescence, DNA repairing and the maintenance of stem cell phenotype. DEK is increasingly recognized as a crucial player in many steps of cancer initiation and progression, and is precisely regulated by abundant promoting and inhibiting factors directly or indirectly. DEK may serve as an architectural modulating protein to regulate the expression and function of multiple human genes in cancer cells...
May 21, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28529938/senescence-inflammatory-regulation-of-reparative-cellular-reprogramming-in-aging-and-cancer
#12
Javier A Menendez, Tomás Alarcón
The inability of adult tissues to transitorily generate cells with functional stem cell-like properties is a major obstacle to tissue self-repair. Nuclear reprogramming-like phenomena that induce a transient acquisition of epigenetic plasticity and phenotype malleability may constitute a reparative route through which human tissues respond to injury, stress, and disease. However, tissue rejuvenation should involve not only the transient epigenetic reprogramming of differentiated cells, but also the committed re-acquisition of the original or alternative committed cell fate...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28529156/transgenerational-effects-of-maternal-and-grandmaternal-age-on-offspring-viability-and-performance-in-drosophila-melanogaster
#13
Margaret C Bloch Qazi, Paige B Miller, Penny M Poeschel, Mai H Phan, Joseph L Thayer, Christian L Medrano
In non-social insects, fitness is determined by relative lifetime fertility. Fertility generally declines with age as a part of senescence. For females, senescence has profound effects on fitness by decreasing viability and fertility as well as those of her offspring. However, important aspects of these maternal effects, including the cause(s) of reduced offspring performance and carry-over effects of maternal age, are poorly understood. Drosophila melanogaster is a useful system for examining potential transgenerational effects of increasing maternal age, because of their use as a model system for studying the physiology and genetic architecture of both reproduction and senescence...
May 18, 2017: Journal of Insect Physiology
https://www.readbyqxmd.com/read/28529078/hcsgd-an-integrated-database-of-human-cellular-senescence-genes
#14
Qiongye Dong, Hongqing Han, Xuehui Liu, Lei Wei, Wei Zhang, Zhen Zhao, Michael Q Zhang, Xiaowo Wang
Cellular senescence is an irreversible cell cycle arrest program in response to various exogenous and endogenous stimuli like telomere dysfunction and DNA damage. It has been widely accepted as an anti-tumor program and is also found closely related to embryo development, tissue repair, organismal aging and age-related degenerative diseases. In the past decades, numerous efforts have been made to uncover the gene regulatory mechanisms of cellular senescence. There is a strong demand to integrate these data from various resources into one open platform...
April 29, 2017: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/28529064/analysis-of-post-transcriptional-regulation-during-cancer-progression-using-a-donor-derived-isogenic-model-of-tumorigenesis
#15
Laura S Bisogno, Jack D Keene
Post-transcriptional regulation of gene expression by RNA binding proteins (RBPs) and non-coding RNAs plays an important role in global gene expression. Many post-transcriptional regulators are misexpressed and misregulated in cancers, resulting in altered programs of protein biosynthesis that can drive tumor progression. While comparative studies of several RBPs and microRNAs expressed in various cancer types have been reported, a model system that can be used to quantify RBP regulation and functional outcomes during the initiation and early stages of tumorigenesis is lacking...
May 18, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28528951/polysaccharides-from-sargassum-thunbergii-monthly-variations-and-anti-complement-and-anti-tumour-activities
#16
Weihua Jin, Ge Liu, Weihong Zhong, Chaomin Sun, Quanbin Zhang
Monthly variations of polysaccharides from Sargassum thunbergii and their anti-complement and anti-tumour activities were investigated. It was observed that an increase in fucose and total sugar contents occurred during the growth period (from early April to mid-June), accompanied by a decrease in molar ratios of other monosaccharides to fucose. The highest yields were obtained from early July to early September, which was in accordance with the significant increase in molar ratio of glucose to fucose and decrease in molar ratio of other monosaccharides to fucose...
May 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28528915/sphingosine-metabolism-as-a-therapeutic-target-in-cutaneous-melanoma
#17
REVIEW
Mohammed Dany
Melanoma is by far the most aggressive type of skin cancer with a poor prognosis in its advanced stages. Understanding the mechanisms involved in melanoma pathogenesis, response, and resistance to treatment has gained a lot of attention worldwide. Recently, the role of sphingolipid metabolism has been studied in cutaneous melanoma. Sphingolipids are bioactive lipid effector molecules involved in the regulation of various cellular signaling pathways such as inflammation, cancer cell proliferation, death, senescence, and metastasis...
May 4, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28527574/nuclear-receptor-tlx-in-development-and-diseases
#18
Guoqiang Sun, Qi Cui, Yanhong Shi
The nuclear receptor TLX (NR2E1) is a transcription factor that is critical for neural development and adult neurogenesis through its actions in regulating neural stem cell proliferation, self-renewal, and fate determination. These roles are primarily executed by regulating TLX downstream target genes involved in myriad pathways such as cell cycle progression, RNA processing, angiogenesis, and senescence. Recent studies suggest that dysregulation of TLX pathways plays an important role in the pathogenesis of human neurological disorders and brain tumors...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28526997/nafld-as-a-sexual-dimorphic-disease-role-of-gender-and-reproductive-status-in-the-development-and-progression-of-nonalcoholic-fatty-liver-disease-and-inherent-cardiovascular-risk
#19
REVIEW
Stefano Ballestri, Fabio Nascimbeni, Enrica Baldelli, Alessandra Marrazzo, Dante Romagnoli, Amedeo Lonardo
Nonalcoholic fatty liver disease (NAFLD) spans steatosis through nonalcoholic steatohepatis, cirrhosis, and hepatocellular carcinoma (HCC) associated with striking systemic features and excess cardiovascular and liver-related mortality. The pathogenesis of NAFLD is complex and multifactorial. Endocrine derangements are closely linked with dysmetabolic traits. For example, in animal and human studies, female sex is protected from dysmetabolism thanks to young individuals' ability to partition fatty acids towards ketone body production rather than very low density lipoprotein (VLDL)-triacylglycerol, and to sex-specific browning of white adipose tissue...
May 19, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28526854/induction-of-senescence-in-primary-glioblastoma-cells-by-serum-and-tgf%C3%AE
#20
Ritesh Kumar, Alexander Gont, Theodore J Perkins, Jennifer E L Hanson, Ian A J Lorimer
Glioblastoma is the most common type of adult brain tumour and has a median survival after diagnosis of a little more than a year. Glioblastomas have a high frequency of mutations in the TERT promoter and CDKN2A locus that are expected to render them resistant to both replicative and oncogene-induced senescence. However, exposure of PriGO8A primary glioblastoma cells to media with 10% serum induced a senescence-like phenotype characterized by increased senescence-associated β galactosidase activity, PML bodies and p21 and morphological changes typical of senescence...
May 19, 2017: Scientific Reports
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