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Cell Death & Disease

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https://www.readbyqxmd.com/read/27906191/discovery-of-a-novel-target-for-cancer-prr14
#1
Shaowen Xiao, Mei Yang
No abstract text is available yet for this article.
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906190/robust-high-throughput-kinetic-analysis-of-apoptosis-with-real-time-high-content-live-cell-imaging
#2
Jesse D Gelles, Jerry Edward Chipuk
Quantitative and kinetic analyses of apoptotic cell death are integral components of exploring cell biology, measuring cellular stress responses, and performing high-throughput genomic/RNAi/drug screens. Here, we present a detailed method that integrates robust kinetic real-time high-content imaging with Annexin V labelling to provide a highly sensitive, accurate, simple and zero-handling approach to quantify extrinsic and intrinsic inducers of apoptosis. The sensitivity of this non-toxic method outperforms previous high-throughput methodologies using viability dyes or caspase-activation reporters...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906189/distinct-outcomes-of-crl-nedd8-pathway-inhibition-reveal-cancer-cell-plasticity
#3
Anastasia V Rulina, Frédérique Mittler, Patricia Obeid, Sophie Gerbaud, Laurent Guyon, Eric Sulpice, Frédérique Kermarrec, Nicole Assard, Monika E Dolega, Xavier Gidrol, Maxim Y Balakirev
Inhibition of protein degradation by blocking Cullin-RING E3 ligases (CRLs) is a new approach in cancer therapy though of unknown risk because CRL inhibition may stabilize both oncoproteins and tumor suppressors. Probing CRLs in prostate cancer cells revealed a remarkable plasticity of cells with TMPRSS2-ERG translocation. CRL suppression by chemical inhibition or knockdown of RING component RBX1 led to reversible G0/G1 cell cycle arrest that prevented cell apoptosis. Conversely, complete blocking of CRLs at a higher inhibitor dose-induced cytotoxicity that was amplified by knockdown of CRL regulator Cand1...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906188/large-scale-pharmacological-profiling-of-3d-tumor-models-of-cancer-cells
#4
Lesley A Mathews Griner, Xiaohu Zhang, Rajarshi Guha, Crystal McKnight, Ian S Goldlust, Madhu Lal-Nag, Kelli Wilson, Sam Michael, Steve Titus, Paul Shinn, Craig J Thomas, Marc Ferrer
The discovery of chemotherapeutic agents for the treatment of cancer commonly uses cell proliferation assays in which cells grow as two-dimensional (2D) monolayers. Compounds identified using 2D monolayer assays often fail to advance during clinical development, most likely because these assays do not reproduce the cellular complexity of tumors and their microenvironment in vivo. The use of three-dimensional (3D) cellular systems have been explored as enabling more predictive in vitro tumor models for drug discovery...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906187/systemic-application-of-3-methyladenine-markedly-inhibited-atherosclerotic-lesion-in-apoe-mice-by-modulating-autophagy-foam-cell-formation-and-immune-negative-molecules
#5
Shen Dai, Bo Wang, Wen Li, Liyang Wang, Xingguo Song, Chun Guo, Yulan Li, Fengming Liu, Faliang Zhu, Qun Wang, Xiaoyan Wang, Yongyu Shi, Jianing Wang, Wei Zhao, Lining Zhang
A growing body of evidence demonstrates that autophagy, an evolutionarily conserved intracellular degradation process, is involved in the pathogenesis of atherosclerosis and has become a potential therapeutic target. Here we tested the effect of two inhibitors of phosphatidylinositol 3-kinase, 3-methyladenine (3-MA) and 2-(4-morpholinyl)-8-phenyl-chromone (LY294002), commonly used as inhibitors of autophagy, in atherosclerosis in apolipoprotein E(-/-) mice. Systemic application of 3-MA but not LY294002 markedly reduced the size of atherosclerotic plaque and increased the stability of lesions in high-fat diet-fed mice as compared with controls...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906186/preimplantation-factor-is-an-anti-apoptotic-effector-in-human-trophoblasts-involving-p53-signaling-pathway
#6
Hadia Moindjie, Esther Dos Santos, Rita-Josiane Gouesse, Nelly Swierkowski-Blanchard, Valérie Serazin, Eytan R Barnea, François Vialard, Marie-Noëlle Dieudonné
From the earliest stages of gestation, embryonic-maternal interaction has a key role in a successful pregnancy. Various factors present during gestation may significantly influence this type of juxta/paracrine interaction. PreImplantation Factor (PIF) is a recently identified factor with activity at the fetomaternal interface. PIF is secreted by viable embryos and directly controls placental development by increasing the invasive capacity of human extravillous trophoblasts (EVTs). To further specify PIF's role in the human placenta, we analyzed the genome-wide expression profile of the EVT in the presence of a synthetic PIF analog (sPIF)...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906185/anti-proliferative-activity-of-the-npm1-interacting-natural-product-avrainvillamide-in-acute-myeloid-leukemia
#7
Vibeke Andresen, Bjarte S Erikstein, Herschel Mukherjee, André Sulen, Mihaela Popa, Steinar Sørnes, Håkon Reikvam, Kok-Ping Chan, Randi Hovland, Emmet McCormack, Øystein Bruserud, Andrew G Myers, Bjørn T Gjertsen
Mutated nucleophosmin 1 (NPM1) acts as a proto-oncogene and is present in ~30% of patients with acute myeloid leukemia (AML). Here we examined the in vitro and in vivo anti-leukemic activity of the NPM1 and chromosome region maintenance 1 homolog (CRM1) interacting natural product avrainvillamide (AVA) and a fully syntetic AVA analog. The NPM1-mutated cell line OCI-AML3 and normal karyotype primary AML cells with NPM1 mutations were significantly more sensitive towards AVA than cells expressing wild-type (wt) NPM1...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906184/1-methyl-tryptophan-attenuates-regulatory-t-cells-differentiation-due-to-the-inhibition-of-estrogen-ido1-mrc2-axis-in-endometriosis
#8
Chunyan Wei, Jie Mei, Lingli Tang, Yukai Liu, Dajin Li, Mingqing Li, Xiaoyong Zhu
Foxp3(+) regulatory T (Treg) cells contribute to the local dysfunctional immune environment in endometriosis, an estrogen-dependent gynecological disease, which affects the function of ectopic endometrial tissue clearance by the immune system. The reason for the high percentage of peritoneal Treg in endometriosis patients is unknown. Here, we show that the proportion of peritoneal Treg cells increases as endometriosis progresses. To determine the probable mechanism, we established a naive T cell-macrophage-endometrial stromal cell (ESC) co-culture system to mimic the peritoneal cavity microenvironment...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906183/male-sterility-in-mcl-1-flox-mice-is-not-due-to-enhanced-mcl1-protein-stability
#9
Casey Ah-Cann, Maximilien Tailler, Andrew J Kueh, Marco J Herold, Joseph T Opferman, Marie-Liesse Asselin-Labat, Philippe Bouillet
No abstract text is available yet for this article.
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906182/bcl-3-regulates-tgf%C3%AE-signaling-by-stabilizing-smad3-during-breast-cancer-pulmonary-metastasis
#10
Xi Chen, Xinwei Cao, Xiaohua Sun, Rong Lei, Pengfei Chen, Yongxu Zhao, Yuhang Jiang, Jie Yin, Ran Chen, Deji Ye, Qi Wang, Zhanjie Liu, Sanhong Liu, Chunyan Cheng, Jie Mao, Yingyong Hou, Mingliang Wang, Ulrich Siebenlist, Y Eugene Chin, Ying Wang, Liu Cao, Guohong Hu, Xiaoren Zhang
Transforming growth factor beta (TGFβ) signaling in breast cancer is selectively associated with pulmonary metastasis. However, the underlying mechanisms remain unclear. Here we show that Bcl-3, a member of the IκB family, serves as a critical regulator in TGFβ signaling to modulate breast cancer pulmonary metastasis. Bcl-3 expression was significantly associated with metastasis-free survival in breast cancer patients. Bcl-3 deletion inhibited the migration and invasion of breast cancer cells in vitro, as well as breast cancer lung metastasis in vivo...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906181/stat6-deficiency-ameliorates-graves-disease-severity-by-suppressing-thyroid-epithelial-cell-hyperplasia
#11
Xuechao Jiang, Bingbing Zha, Xiaoming Liu, Ronghua Liu, Jun Liu, Enyu Huang, Tingting Qian, Jiajing Liu, Zhiming Wang, Dan Zhang, Luman Wang, Yiwei Chu
Signal transducer and activator of transcription 6 (STAT6) is involved in epithelial cell growth. However, little is known regarding the STAT6 phosphorylation status in Graves' disease (GD) and its role in thyroid epithelial cells (TECs). In this study, we found that STAT6 phosphorylation (p-STAT6) was significantly increased in TECs from both GD patients and experimental autoimmune Graves' disease mice and that STAT6 deficiency ameliorated GD symptoms. Autocrine IL-4 signalling in TECs activated the phosphorylation of STAT6 via IL-4 R engagement, and the downstream targets of STAT6 were Bcl-xL and cyclin D1...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906180/mir-148a-3p-represses-proliferation-and-emt-by-establishing-regulatory-circuits-between-erbb3-akt2-c-myc-and-dnmt1-in-bladder-cancer
#12
Xiao Wang, Zhen Liang, Xin Xu, Jiangfeng Li, Yi Zhu, Shuai Meng, Shiqi Li, Song Wang, Bo Xie, Alin Ji, Ben Liu, Xiangyi Zheng, Liping Xie
miR-148a-3p downregulation has emerged as a critical factor in cancer progression yet, the underlying mechanisms of miR-148a-3p expression pattern and its function in bladder cancer remains to be elucidated. Here, we illustrate that miR-148a-3p is frequently downregulated in bladder cancer and that its expression may be regulated by DNA methylation. DNA methyltransferase 1 (DNMT1) and miR-148a-3p function in a positive feedback loop in bladder cancer. miR-148a-3p overexpression functions as a tumor suppressor in bladder cancer cells...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906179/pink1-dependent-phosphorylation-of-pink1-and-parkin-is-essential-for-mitochondrial-quality-control
#13
Na Zhuang, Lin Li, She Chen, Tao Wang
Mitochondrial dysfunction has been linked to the pathogenesis of a large number of inherited diseases in humans, including Parkinson's disease, the second most common neurodegenerative disorder. The Parkinson's disease genes pink1 and parkin, which encode a mitochondrially targeted protein kinase, and an E3 ubiquitin ligase, respectively, participate in a key mitochondrial quality-control pathway that eliminates damaged mitochondria. In the current study, we established an in vivo PINK1/Parkin-induced photoreceptor neuron degeneration model in Drosophila with the aim of dissecting the PINK1/Parkin pathway in detail...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906178/a-mechanism-for-overcoming-p-glycoprotein-mediated-drug-resistance-novel-combination-therapy-that-releases-stored-doxorubicin-from-lysosomes-via-lysosomal-permeabilization-using-dp44mt-or-dpc
#14
Nicole A Seebacher, Des R Richardson, Patric J Jansson
The intracellular distribution of a drug can cause significant variability in both activity and selectivity. Herein, we investigate the mechanism by which the anti-cancer agents, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) and the clinically trialed, di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), re-instate the efficacy of doxorubicin (DOX), in drug-resistant P-glycoprotein (Pgp)-expressing cells. Both Dp44mT and DpC potently target and kill Pgp-expressing tumors, while DOX effectively kills non-Pgp-expressing cancers...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906177/-normalizing-the-malignant-phenotype-of-luminal-breast-cancer-cells-via-alpha-v-beta-3-integrin
#15
Hanan Abu-Tayeh, Keren Weidenfeld, Alisa Zhilin-Roth, Sagi Schif-Zuck, Sonja Thaler, Cristina Cotarelo, Tuan Z Tan, Jean P Thiery, Jeffrey E Green, Geula Klorin, Edmond Sabo, Jonathan P Sleeman, Maty Tzukerman, Dalit Barkan
Reestablishing tissue organization of breast cancer cells into acini was previously shown to override their malignant phenotype. In our study, we demonstrate that alpha(v)beta(3) integrin (Int-αvβ3), previously shown to play a role in cancer progression, promoted differentiation and growth arrest of organoids derived from luminal A breast cancer cells grown in their relevant three-dimensional microenvironment. These organoids differentiated into normal-like acini resembling a benign stage of breast tissue...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906176/epigenetic-programming-of-dnmt3a-mediated-by-ap2%C3%AE-is-required-for-granting-preadipocyte-the-ability-to-differentiate
#16
Wei Guo, Jiangnan Chen, Ying Yang, Jianbei Zhu, Jiarui Wu
Adipogenesis has an important role in regulating energy homeostasis in mammals. 3T3-L1 preadipocytes have been widely used as an in vitro model for analyzing the molecular mechanism of adipogenesis. Previous reports indicated that the stage of contact inhibition (CI), through which the proliferating cells exit from the cell cycle, was required for granting preadipocyte the ability to differentiate. While this kind of the granting mechanism remains elusive. In the present study, we showed that DNA (cytosine-5) methyltransferase 3a (Dnmt3a) was upregulated at both the mRNA and protein level during the CI stage, and resulted in increasing promoter methylation of adipogenic genes...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906175/impaired-haematopoietic-stem-cell-differentiation-and-enhanced-skewing-towards-myeloid-progenitors-in-aged-caspase-2-deficient-mice
#17
Swati Dawar, Nur Hezrin Shahrin, Nikolina Sladojevic, Richard J D'Andrea, Loretta Dorstyn, Devendra K Hiwase, Sharad Kumar
The apoptotic cysteine protease caspase-2 has been shown to suppress tumourigenesis in mice and its reduced expression correlates with poor prognosis in some human malignancies. Caspase-2-deficient mice develop normally but show ageing-related traits and, when challenged by oncogenic stimuli or certain stress, show enhanced tumour development, often accompanied by extensive aneuploidy. As stem cells are susceptible to acquiring age-related functional defects because of their self-renewal and proliferative capacity, we examined whether loss of caspase-2 promotes such defects with age...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906174/therapeutic-advantage-of-pro-electrophilic-drugs-to-activate-the-nrf2-are-pathway-in-alzheimer-s-disease-models
#18
Stuart A Lipton, Tayebeh Rezaie, Anthony Nutter, Kevin M Lopez, James Parker, Kunio Kosaka, Takumi Satoh, Scott R McKercher, Eliezer Masliah, Nobuki Nakanishi
Alzheimer's disease (AD) is characterized by synaptic and neuronal loss, which occurs at least partially through oxidative stress induced by oligomeric amyloid-β (Aβ)-peptide. Carnosic acid (CA), a chemical found in rosemary and sage, is a pro-electrophilic compound that is converted to its active form by oxidative stress. The active form stimulates the Keap1/Nrf2 transcriptional pathway and thus production of phase 2 antioxidant enzymes. We used both in vitro and in vivo models. For in vitro studies, we evaluated protective effects of CA on primary neurons exposed to oligomeric Aβ...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906173/sensitivity-of-gbm-cells-to-camp-agonist-mediated-apoptosis-correlates-with-cd44-expression-and-agonist-resistance-with-mapk-signaling
#19
Paul M Daniel, Gulay Filiz, Theo Mantamadiotis
In some cell types, activation of the second messenger cAMP leads to increased expression of proapoptotic Bim and subsequent cell death. We demonstrate that suppression of the cAMP pathway is a common event across many cancers and that pharmacological activation of cAMP in glioblastoma (GBM) cells leads to enhanced BIM expression and apoptosis in specific GBM cell types. We identified the MAPK signaling axis as the determinant of cAMP agonist sensitivity in GBM cells, with high MAPK activity corresponding to cAMP resistance and low activity corresponding to sensitization to cAMP-induced apoptosis...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906172/inflammatory-macrophages-can-transdifferentiate-into-myofibroblasts-during-renal-fibrosis
#20
Xiao-Ming Meng, Shuang Wang, Xiao-Ru Huang, Chen Yang, Jun Xiao, Yang Zhang, Ka-Fai To, David J Nikolic-Paterson, Hui-Yao Lan
Myofibroblasts play a central role in renal fibrosis although the origin of these cells remains controversial. We recently reported that bone marrow-derived macrophages can give rise to myofibroblasts through macrophage to myofibroblast transition (MMT). However, several important issues remain to be addressed, including whether MMT occurs in human kidney disease and verification of the MMT process through lineage tracing. Biopsies from a cohort of 58 patients with various forms of kidney disease were examined for MMT cells that co-express macrophage (CD68) and myofibroblast (α-smooth muscle actin, α-SMA) markers...
December 1, 2016: Cell Death & Disease
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