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Cell Death & Disease

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https://www.readbyqxmd.com/read/28425987/biological-activity-of-tumor-treating-fields-in-preclinical-glioma-models
#1
Manuela Silginer, Michael Weller, Roger Stupp, Patrick Roth
Glioblastoma is the most common and aggressive form of intrinsic brain tumor with a very poor prognosis. Thus, novel therapeutic approaches are urgently needed. Tumor-treating fields (TTFields) may represent such a novel treatment option. The aim of this study was to investigate the effects of TTFields on glioma cells, as well as the functional characterization of the underlying mechanisms. Here, we assessed the anti-glioma activity of TTFields in several preclinical models. Applying TTFields resulted in the induction of cell death in a frequency- and intensity-dependent manner in long-term glioma cell lines, as well as glioma-initiating cells...
April 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28425986/p16ink4a-upregulation-mediated-by-tbk1-induces-retinal-ganglion-cell-senescence-in-ischemic-injury
#2
L U Li, Yin Zhao, Hong Zhang
Glaucoma is a leading cause of irreversible blindness worldwide that is characterized by progressive retinal ganglion cell (RGC) death. However, RGC senescence as a phase before RGC death, and the mechanism of RGC senescence remains unclear. Here, we demonstrate that TANK-binding protein 1 (TBK1) is upregulated in acute IOP elevation-induced ischemic retinas mouse model. Moreover, pre-treatment with the TBK1 inhibitor BX-795 reduced p16INK4a (p16) expression and RGC senescence. Upregulation of TBK1 via plasmid transfection increased Akt phosphorylation at Ser473 and Bmi1 phosphorylation...
April 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28425985/the-cellular-senescence-of-leukemia-initiating-cells-from-acute-lymphoblastic-leukemia-is-postponed-by-%C3%AE-arrestin1-binding-with-p300-sp1-to-regulate-htert-transcription
#3
Shan Liu, Haiyan Liu, Ru Qin, Yi Shu, Zhidai Liu, Penghui Zhang, Caiwen Duan, Dengli Hong, Jie Yu, Lin Zou
Although we previously reported that the self-renewal of leukemia-initiating cells of B-lineage acute lymphoblastic leukemia (B-ALL LICs) was regulated by β-Arrestin1, a multiple-function protein, the cellular senescence is critical for LICs fate and leukemia progress, and worthy for further investigation. Here we found that depletion of β-Arrestin1 extended the population doubling time and the percentage of senile cells, the signatures of cellular senescence, of B-ALL LICs. Moreover, lack of β-Arrestin1 enhanced the expression of proteins (CBX, HIRA) and genes (P53, P16) related to senescence in leukemic Reh cells and B-ALL-LICs-derived leukemic mice...
April 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28425984/withaferin-a-kills-cancer-cells-with-and-without-telomerase-chemical-computational-and-experimental-evidences
#4
Yue Yu, Shashank P Katiyar, Durai Sundar, Zeenia Kaul, Eijiro Miyako, Zhenya Zhang, Sunil C Kaul, Roger R Reddel, Renu Wadhwa
Maintenance of telomere length is the most consistent attribute of cancer cells. Tightly connected to their capacity to overcome replicative mortality, it is achieved either by activation of telomerase or an Alternative mechanism of Lengthening of Telomeres (ALT). Disruption of either of these mechanisms has been shown to induce DNA damage signalling leading to senescence or apoptosis. Telomerase inhibitors are considered as potential anticancer drugs but are ineffective for ALT cancers (~15% of all cancers)...
April 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28406483/apr-246-prima-1-met-inhibits-thioredoxin-reductase-1-and-converts-the-enzyme-to-a-dedicated-nadph-oxidase
#5
Xiaoxiao Peng, Mei-Qiong-Zi Zhang, Francesca Conserva, Gihan Hosny, Galina Selivanova, Vladimir Jn Bykov, Elias Sj Arnér, Klas G Wiman
No abstract text is available yet for this article.
April 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28406482/cisplatin-enriching-cancer-stem-cells-confer-multidrug-resistance-in-non-small-cell-lung-cancer-via-enhancing-trib1-hdac-activity
#6
Lihui Wang, Xing Liu, Yong Ren, Jingyuan Zhang, Junli Chen, Wenlong Zhou, Wei Guo, Xiaoxuan Wang, Huiping Chen, Meng Li, Xiangzhong Yuan, Xun Zhang, Jingyu Yang, Chunfu Wu
Chemotherapeutic agents are generally used as a frontline therapy for non-small cell lung cancer (NSCLC). However, resistance to chemotherapy arises rapidly in NSCLC, and the reasons for chemotherapy resistance have not been fully determined. Here, we found cisplatin, but not paclitaxel and doxorubicin, induced the enrichment of cancer stem cell (CSC) and conferred multidrug resistance in NSCLC cell lines. In vivo study confirmed drug-resistant tumors displayed the enhanced expressions of CSC transcription factors...
April 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28406481/liver-receptor-homolog-1-nr5a2-regulates-cd95-fas-ligand-transcription-and-associated-t-cell-effector-functions
#7
Juliane Schwaderer, Ann-Kathrin Gaiser, Truong San Phan, MEugenia Delgado, Thomas Brunner
CD95/Fas ligand (FasL) is a cell death-promoting member of the tumor necrosis factor family with important functions in the regulation of T-cell homeostasis and cytotoxicity. In T cells, FasL expression is tightly regulated on a transcriptional level involving a complex set of different transcription factors. The orphan nuclear receptor liver receptor homolog-1 (LRH-1/NR5a2) is involved in the regulation of development, lipid metabolism and proliferation and is predominantly expressed in epithelial tissues...
April 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28406480/wdr79-promotes-the-proliferation-of-non-small-cell-lung-cancer-cells-via-usp7-mediated-regulation-of-the-mdm2-p53-pathway
#8
Yang Sun, Lanqin Cao, Xunan Sheng, Jieying Chen, Yu Zhou, Chao Yang, Tanggang Deng, Hongchang Ma, Peifu Feng, Jing Liu, Weihong Tan, Mao Ye
WD repeat protein 79 (WDR79) is a member of the WD-repeat protein family and functions as a scaffold protein during telomerase assembly, Cajal body formation and DNA double strand break repair. We have previously shown that WDR79 is frequently overexpressed in cell lines and tissues derived from non-small cell lung cancer (NSCLC) and it accelerates cell proliferation in NSCLC. However, the detailed mechanism underlying the role of WDR79 in the proliferation of NSCLC cells remains unclear. Here, we report the discovery of a molecular interaction between WDR79 and USP7 and show its functional significance in linking the Mdm2-p53 pathway to the proliferation of NSCLC cells...
April 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28406479/foot-and-mouth-disease-virus-infection-inhibits-lgp2-protein-expression-to-exaggerate-inflammatory-response-and-promote-viral-replication
#9
Zixiang Zhu, Chuntian Li, Xiaoli Du, Guoqing Wang, Weijun Cao, Fan Yang, Huanhuan Feng, Xiangle Zhang, Zhengwang Shi, Huanan Liu, Hong Tian, Dan Li, Keshan Zhang, Xiangtao Liu, Haixue Zheng
The role of the innate immune protein LGP2 (laboratory of genetics and physiology 2) in FMDV-infected cells remains unknown. Here, we demonstrate the antiviral role of LGP2 during FMDV infection. FMDV infection triggered LGP2 mRNA expression but reduced protein expression. Overexpression of LGP2 suppressed FMDV replication, and the inflammatory response was significantly inhibited by LGP2 in virus-infected cells. The N-terminal DExDc and the C-terminal regulatory domain regions of LGP2 were essential for LGP2-mediated antiviral activity against FMDV...
April 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28406478/the-suppression-of-apoptosis-by-%C3%AE-herpesvirus
#10
REVIEW
Yu You, An-Chun Cheng, Ming-Shu Wang, Ren-Yong Jia, Kun-Feng Sun, Qiao Yang, Ying Wu, Dekang Zhu, Shun Chen, Ma-Feng Liu, Xin-Xin Zhao, Xiao-Yue Chen
Apoptosis, an important innate immune mechanism that eliminates pathogen-infected cells, is primarily triggered by two signalling pathways: the death receptor pathway and the mitochondria-mediated pathway. However, many viruses have evolved various strategies to suppress apoptosis by encoding anti-apoptotic factors or regulating apoptotic signalling pathways, which promote viral propagation and evasion of the host defence. During its life cycle, α-herpesvirus utilizes an elegant multifarious anti-apoptotic strategy to suppress programmed cell death...
April 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28406477/mir-21-ablation-and-obeticholic-acid-ameliorate-nonalcoholic-steatohepatitis-in-mice
#11
Pedro M Rodrigues, Marta B Afonso, André L Simão, Catarina C Carvalho, Alexandre Trindade, António Duarte, Pedro M Borralho, Mariana V Machado, Helena Cortez-Pinto, Cecília Mp Rodrigues, Rui E Castro
microRNAs were recently suggested to contribute to the pathogenesis of nonalcoholic fatty liver disease (NAFLD), a disease lacking specific pharmacological treatments. In that regard, nuclear receptors are arising as key molecular targets for the treatment of nonalcoholic steatohepatitis (NASH). Here we show that, in a typical model of NASH-associated liver damage, microRNA-21 (miR-21) ablation results in a progressive decrease in steatosis, inflammation and lipoapoptosis, with impairment of fibrosis. In a complementary fast food (FF) diet NASH model, mimicking features of the metabolic syndrome, miR-21 levels increase in both liver and muscle, concomitantly with decreased expression of peroxisome proliferator-activated receptor α (PPARα), a key miR-21 target...
April 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28406476/wisp-1-positively-regulates-angiogenesis-by-controlling-vegf-a-expression-in-human-osteosarcoma
#12
Hsiao-Chi Tsai, Huey-En Tzeng, Chun-Yin Huang, Yuan-Li Huang, Chun-Hao Tsai, Shih-Wei Wang, Po-Chuan Wang, An-Chen Chang, Yi-Chin Fong, Chih-Hsin Tang
In recent years, much research has focused on the role of angiogenesis in osteosarcoma, which occurs predominantly in adolescents and young adults. The vascular endothelial growth factor-A (VEGF-A) pathway is the key regulator of angiogenesis and in osteosarcoma. VEGF-A expression has been recognized as a prognostic marker in angiogenesis. Aberrant WNT1-inducible signaling pathway protein-1 (WISP-1) expression is associated with various cancers. However, the function of WISP-1 in osteosarcoma angiogenesis is poorly understood...
April 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28406475/depletion-of-polycomb-repressive-complex-2-core-component-eed-impairs-fetal-hematopoiesis
#13
Wenhua Yu, Fang Zhang, Shiyan Wang, Yi Fu, Jiahuan Chen, Xiaodong Liang, Huangying Le, William T Pu, Bing Zhang
Polycomb repressive complex 2 (PRC2), a H3K27me3 methyltransferase complex, promotes the development of many organs by silencing ectopic transcription program. However, currently little is known about the role of PRC2 in blood and vascular development. In this study, we interrogated the function of embryonic ectoderm development (EED), a core PRC2 component, in both endothelial and hematopoietic tissues by inactivating a floxed murine EED allele with Tie2Cre, which catalyzes recombination in endothelial and hematopoietic lineages...
April 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28383563/deregulated-ajap1-%C3%AE-catenin-zeb1-signaling-promotes-hepatocellular-carcinoma-carcinogenesis-and-metastasis
#14
Jihua Han, Changming Xie, Tiemin Pei, Jiabei Wang, Yaliang Lan, Kaihua Huang, Yifeng Cui, Fengyue Wang, Jiewu Zhang, Shangha Pan, Yingjian Liang, Tongsen Zhen, Ruipeng Song, Boshi Sun, Yuejin Li, Huawen Shi, Guangchao Yang, Xirui Liu, Mingxi Zhu, Yan Wang, Keyu Li, Yao Liu, Fanzheng Meng, Fei Liao, Xianzhi Meng, Xuehui Hong, Lianxin Liu
Adherens junctions-associated protein 1 (AJAP1) is an integral membrane protein that is thought to function as a tumor suppressor in various malignancies. Downregulation of AJAP1 mRNA levels may predict recurrence in hepatocellular carcinoma (HCC) patients, but the underlying molecular mechanism is unknown. This was addressed in the present study by examining the role of AJAP1 in HCC cell proliferation, migration, and invasion in vitro as well as in human specimens and mouse xenograft model. We found that AJAP1 expression was reduced in HCC cells and human HCC tissue, which was associated with metastasis...
April 6, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28383562/vps35-regulates-parkin-substrate-aimp2-toxicity-by-facilitating-lysosomal-clearance-of-aimp2
#15
Seung Pil Yun, Hyojung Kim, Sangwoo Ham, Seung-Hwan Kwon, Gum Hwa Lee, Joo-Ho Shin, Sang Hun Lee, Han Seok Ko, Yunjong Lee
Vacuolar protein sorting-associated protein 35 (VPS35) is involved in retrograde transport of proteins from endosomes to trans-Golgi network. Gene mutations in VPS35 are linked to autosomal dominant late-onset Parkinson's disease (PD). Although the identification of VPS35 mutations has provided novel insight about its interactions with several PD-associated genes including leucine-rich repeat kinase 2 (LRRK2) and α-synuclein, little information is available about the molecular mechanisms of cell death downstream of VPS35 dysfunction...
April 6, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28383561/mir-10a-suppresses-colorectal-cancer-metastasis-by-modulating-the-epithelial-to-mesenchymal-transition-and-anoikis
#16
Yankun Liu, Yingnan Zhang, Haidong Wu, Yufeng Li, Yi Zhang, Min Liu, Xin Li, Hua Tang
MicroRNAs (miRNAs) have a critical role in tumorigenesis and metastasis, which are major obstacles of cancer therapy. However, the role of miRNAs in colorectal cancer (CRC) metastasis remains poorly understood. Here, we found that miRNA-10a (miR-10a) was upregulated in primary CRC tissues and cell line (SW480) derived from primary CRC compared with metastatic cancer tissues in lymph node and cell line (SW620). The differential expression of miR-10a was inversely correlated with distant metastasis and invasion depth...
April 6, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28383560/induction-of-autophagy-by-spermidine-is-neuroprotective-via-inhibition-of-caspase-3-mediated-beclin-1-cleavage
#17
Yi Yang, Sicong Chen, Yuqing Zhang, Xiaoxia Lin, Yiyin Song, Zhaoliang Xue, Haoran Qian, Shanshan Wang, Guihua Wan, Xiaoxiang Zheng, Lihui Zhang
Spermidine, a natural polyamine presented widely in mammalian cells, has been implicated to extend the lifespan of several model organisms by inducing autophagy. However, the effect of spermidine against neuronal damage has not yet been fully determined. In this study, neuronal cell injury was induced by treating PC12 cells and cortical neurons with 1 μM staurosporine (STS). We found that STS-induced cell injury could be efficiently attenuated by pretreatment with 1 mM spermidine. Spermidine inhibited the caspase 3 activation induced by STS...
April 6, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28383559/erythropoietin-protects-against-rhabdomyolysis-induced-acute-kidney-injury-by-modulating-macrophage-polarization
#18
Shuo Wang, Chao Zhang, Jiawei Li, Sidikejiang Niyazi, Long Zheng, Ming Xu, Ruiming Rong, Cheng Yang, Tongyu Zhu
Erythropoietin (EPO) is a well-known hormone that is clinically used for the treatment of anemia. Very recently, an increasing body of evidence showed that EPO could still regulate bioactivities of macrophages. However, the details about the immunomodulatory effect of EPO on macrophages are not fully delineated, particularly in the setting of renal damages. Therefore, in the present study, we determined whether EPO could exert an impact on the dynamics of macrophages in a well-established model of rhabdomyolysis-induced acute kidney injury and explored the potential mechanisms...
April 6, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28383558/extracellular-cystatin-sn-and-cathepsin-b-prevent-cellular-senescence-by-inhibiting-abnormal-glycogen-accumulation
#19
Sang-Seok Oh, Soojong Park, Ki-Won Lee, Hamadi Madhi, Sae Gwang Park, Hee Gu Lee, Yong-Yeon Cho, Jiyun Yoo, Kwang Dong Kim
Cystatin SN (CST1), a known inhibitor of cathepsin B (CatB), has important roles in tumor development. Paradoxically, CatB is a member of the cysteine cathepsin family that acts in cellular processes, such as tumor development and invasion. However, the relationship between CST1 and CatB, and their roles in tumor development are poorly understood. In this study, we observed that the knockdown of CST1 induced the activity of senescence-associated β-galactosidase, a marker of cellular senescence, and expression of senescence-associated secretory phenotype genes, including interleukin-6 and chemokine (C-C motif) ligand 20, in MDA-MB-231 and SW480 cancer cells...
April 6, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28383557/silencing-nkg2d-ligand-targeting-mirnas-enhances-natural-killer-cell-mediated-cytotoxicity-in-breast-cancer
#20
Jiaying Shen, Jie Pan, Chengyong Du, Wengong Si, Minya Yao, Liang Xu, Huilin Zheng, Mingjie Xu, Danni Chen, Shu Wang, Peifen Fu, Weimin Fan
NKG2D is one of the major activating receptors of natural killer (NK) cells and binds to several ligands (NKG2DLs). NKG2DLs are expressed on malignant cells and sensitize them to early elimination by cytotoxic lymphocytes. We investigated the clinical importance of NKG2DLs and the mechanism of NKG2DL regulation in breast cancer (BC). Among the NKG2DLs MICA/B and ULBP1/2/3, the expression levels of MICA/B in BC tissues were inversely associated with the Tumor Node Metastasis stage. We first found that the high expression of MICB, but not MICA, was an independent prognostic factor for overall survival in patients with BC...
April 6, 2017: Cell Death & Disease
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