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https://www.readbyqxmd.com/read/29333953/the-irreversible-erbb1-2-4-inhibitor-neratinib-interacts-with-the-bcl-2-inhibitor-venetoclax-to-kill-mammary-cancer-cells
#1
Laurence Booth, Jane L Roberts, Francesca Avogadri-Connors, Richard E CutlerJr, Alshad S Lalani, Andrew Poklepovic, Paul Dent
The irreversible ERBB1/2/4 inhibitor, neratinib, down-regulates the expression of ERBB1/2/4 as well as the levels of MCL-1 and BCL-XL. Venetoclax (ABT199) is a BCL-2 inhibitor. At physiologic concentrations neratinib interacted in a synergistic fashion with venetoclax to kill HER2+ and TNBC mammary carcinoma cells. This was associated with the drug-combination: reducing the expression and phosphorylation of ERBB1/2/3; in an eIF2α-dependent fashion reducing the expression of MCL-1 and BCL-XL and increasing the expression of Beclin1 and ATG5; and increasing the activity of the ATM-AMPKα-ULK1 S317 pathway which was causal in the formation of toxic autophagosomes...
January 15, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29333768/-effects-of-geranylgeranyltransferase-%C3%A2-gene-silencing-by-rna-interference-on-the-migration-and-invasion-of-tongue-carcinoma
#2
Chen Zhenggang, Wang Shuren, Li Jinghua, Han Jinhong, Wang Qimin, Tong Lei, Liu Wenjun, Yang Fang, Guo Qingyuan, Guo Dawei, Wang Ying
OBJECTIVE: RNA interference was used to silence geranylgeranyltransferase Ⅰ(GGTase-Ⅰ) in vitro and to study the effect of GGTase-Ⅰ on the migration and invasion of tongue squamous cancer cells. METHODS: Three small interfering RNAs (siRNA) were designed according to the GGTase-Ⅰ sequence by Genebank and were transfected into tongue squamous cancer cells Cal-27 to knock down GGTase-Ⅰ expression. The tested cells were divided into three groups, as follows: the RNA-interfered groups (GGTase-Ⅰ siRNA1, GGTase-Ⅰ siRNA 2, GGTase-Ⅰ siRNA 3), a negative control group (disrupted by random sequence NC-siRNA), and a blank control group...
December 1, 2017: Hua Xi Kou Qiang Yi Xue za Zhi, Huaxi Kouqiang Yixue Zazhi, West China Journal of Stomatology
https://www.readbyqxmd.com/read/29332334/mir429-expression-level-in-renal-cell-cancer-and-its-correlation-with-the-prognosis-of-patients
#3
Zhan-Kun Wang, Lei Luo, Zhao-Jin Du, Gui-Ming Zhang, Li-Jiang Sun
PURPOSE: To test the hypothesis that miR429 expression in renal cancer patients is increased and plays a role in the pathogenesis of the disease. METHODS: Twenty-seven renal cancer patients admitted to our hospital from May 2014 to May 2015 were enrolled as the study group, and 28 non-cancer patients were selected during the same period as the control group. Renal biopsy and serum samples were used to detect miR429 expression levels, and the patient histories were obtained to make relevant associations to clinical outcomes...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29330772/rice-wrky11-plays-a-role-in-pathogen-defense-and-drought-tolerance
#4
Heyoung Lee, Jooyoung Cha, Changhyun Choi, Naeyoung Choi, Hyun-So Ji, Sang Ryeol Park, Seungbum Lee, Duk-Ju Hwang
BACKGROUND: Plants are frequently subjected to abiotic and biotic stresses, and WRKY proteins play a pivotal role in the response to such stress. OsWRKY11 is induced by pathogens, drought, and heat, suggesting a function in biotic and abiotic stress responses. RESULTS: This study identified OsWRKY11, a member of WRKY group IIc. It is a transcriptional activator that localized to the nucleus. Ectopic expression of OsWRKY11 resulted in enhanced resistance to a bacterial pathogen, Xanthomonas oryzae pv...
January 12, 2018: Rice
https://www.readbyqxmd.com/read/29330760/oxidized-phospholipids-stimulate-production-of-stem-cell-factor-via-nrf2-dependent-mechanisms
#5
Taras Afonyushkin, Olga V Oskolkova, Valery N Bochkov
Receptor tyrosine kinase c-Kit and its ligand stem cell factor (SCF) regulate resident vascular wall cells and recruit circulating progenitors. We tested whether SCF may be induced by oxidized palmitoyl-arachidonoyl-phosphatidylcholine (OxPAPC) known to accumulate in atherosclerotic vessels. Gene expression analysis demonstrated OxPAPC-induced upregulation of SCF mRNA and protein in different types of endothelial cells (ECs). Elevated levels of SCF mRNA were observed in aortas of ApoE-/- knockout mice. ECs produced biologically active SCF because conditioned medium from OxPAPC-treated cells stimulated activation (phosphorylation) of c-Kit in naïve ECs...
January 12, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29330493/development-of-versatile-non-homologous-end-joining-based-knock-in-module-for-genome-editing
#6
Shun Sawatsubashi, Yudai Joko, Seiji Fukumoto, Toshio Matsumoto, Shigeo S Sugano
CRISPR/Cas9-based genome editing has dramatically accelerated genome engineering. An important aspect of genome engineering is efficient knock-in technology. For improved knock-in efficiency, the non-homologous end joining (NHEJ) repair pathway has been used over the homology-dependent repair pathway, but there remains a need to reduce the complexity of the preparation of donor vectors. We developed the versatile NHEJ-based knock-in module for genome editing (VIKING). Using the consensus sequence of the time-honored pUC vector to cut donor vectors, any vector with a pUC backbone could be used as the donor vector without customization...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330147/genetic-ablation-of-rbm38-promotes-lymphomagenesis-in-the-context-of-mutant-p53-by-downregulating-pten
#7
Jin Zhang, Enshun Xu, Cong Ren, Hee Jung Yang, Yanhong Zhang, Wenqiang Sun, Xiangmudong Kong, Weici Zhang, Mingyi Chen, Eric C Huang, Xinbin Chen
Mutant p53 exerts gain-of-function effects that drive metastatic progression and therapeutic resistance, but the basis for these effects remain obscure. The RNA binding protein RBM38 limits translation of mutant p53 and is often ablated in tumors harboring it. Here we show how loss of Rbm38 significantly alters cancer susceptibility in mutant p53 knock-in mice, by shortening lifespan, altering tumor incidence and promoting T cell lymphomagenesis. Loss of Rbm38 enhanced mutant p53 expression and decreased expression of the tumor suppressor Pten, a key regulator of T cell development...
January 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29329756/phospholipid-composition-of-the-outer-membrane-of-escherichia-coli-influences-its-susceptibility-against-antimicrobial-peptide-apidaecin-1b
#8
Rico Schmidt, Ding Yonghong, Ralf Hoffmann
Proline-rich antimicrobial peptides (PrAMPs) kill bacteria in a multimodal mechanism by inhibiting the 70S ribosome (i.e., protein translation) as dominant lethal mechanism besides inhibition of several other proteins, such as chaperone DnaK. PrAMPs pass the outer membrane of Gram-negative bacteria, probably by a self-promoted uptake followed by a transporter-mediated uptake from the periplasm. Mutation of transporter protein SbmA is a well-studied resistance mechanism observed in vitro by resistance induction with PrAMPs...
November 21, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/29329586/il-33-st2-signaling-contributes-to-radicular-pain-by-modulating-mapk-and-nf-%C3%AE%C2%BAb-activation-and-inflammatory-mediator-expression-in-the-spinal-cord-in-rat-models-of-noncompressive-lumber-disk-herniation
#9
Si-Jian Huang, Jian-Qin Yan, Hui Luo, Lu-Yao Zhou, Jian-Gang Luo
BACKGROUND: Immune and inflammatory responses occurring in the spinal cord play a pivotal role in the progression of radicular pain caused by intervertebral disk herniation. Interleukin-33 (IL-33) orchestrates inflammatory responses in a wide range of inflammatory and autoimmune disorders of the nervous system. Thus, the purpose of this study is to investigate the expression of IL-33 and its receptor ST2 in the dorsal spinal cord and to elucidate whether the inhibition of spinal IL-33 expression significantly attenuates pain-related behaviors in rat models of noncompressive lumbar disc herniation...
January 12, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29329079/the-interactome-of-ebv-lmp1-evaluated-by-proximity-based-bioid-approach
#10
Mark A Rider, Mujeeb R Cheerathodi, Stephanie N Hurwitz, Dingani Nkosi, Lauren A Howell, Deanna C Tremblay, Xia Liu, Fanxiu Zhu, David G Meckes
Epstein-Barr virus LMP1 is an oncoprotein required for immortalizing B lymphocytes and also plays important roles in transforming non-lymphoid tissue. The discovery of LMP1 protein interactions will likely generate targets to treat EBV-associated cancers. Here, we define the broader LMP1 interactome using the recently developed BioID method. Combined with mass spectrometry, we identified over 1000 proteins across seven independent experiments with direct or indirect relationships to LMP1. Pathway analysis suggests that a significant number of the proteins identified are involved in signal transduction and protein or vesicle trafficking...
January 9, 2018: Virology
https://www.readbyqxmd.com/read/29328485/knockdown-of-hnrnp-a2-b1-inhibits-cell-proliferation-invasion-and-cell-cycle-triggering-apoptosis-in-cervical-cancer-via-pi3k-akt-signaling-pathway
#11
Xiang Shi, Li Ran, Yao Liu, Shu-Huai Zhong, Ping-Ping Zhou, Ming-Xin Liao, Wen Fang
Cervical cancer is currently one of the major threats to women's health. The overexpression of heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) as the biomarker has been investigated in various cancers. In our previous study, we found that lobaplatin induced apoptosis and cell cycle arrest via downregulation of proteins including hnRNP A2/B1 in cervical cancer cells. However, the underlying relationship between hnRNP A2/B1 and cervical cancer remained largely unknown. hnRNP A2/B1 knock‑down in HeLa and CaSki cells was performed by shRNA transfection...
January 5, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29328442/identification-of-differentially-expressed-genes-and-regulatory-relationships-in-huntington-s-disease-by-bioinformatics-analysis
#12
Xiaoyu Dong, Shuyan Cong
Huntington's disease (HD) is an inherited, progressive neurodegenerative disease caused by a CAG expansion in the huntingtin (HTT) gene; various dysfunctions of biological processes in HD have been proposed. However, at present the exact pathogenesis of HD is not fully understood. The present study aimed to explore the pathogenesis of HD using a computational bioinformatics analysis of gene expression. GSE11358 was downloaded from the Gene Expression Omnibus andthe differentially expressed genes (DEGs) in the mutant HTT knock‑in cell model STHdhQ111/Q111 were predicted...
January 9, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29328367/tumorigenic-proteins-upregulated-in-the-mycn-amplified-imr-32-human-neuroblastoma-cells-promote-proliferation-and-migration
#13
Hayat Zaatiti, Jad Abdallah, Zeina Nasr, George Khazen, Anthony Sandler, Tamara J Abou-Antoun
Childhood neuroblastoma is one of the most common types of extra-cranial cancer affecting children with a clinical spectrum ranging from spontaneous regression to malignant and fatal progression. In order to improve the clinical outcomes of children with high-risk neuroblastoma, it is crucial to understand the tumorigenic mechanisms that govern its malignant behaviors. MYCN proto-oncogene, bHLH transcription factor (MYCN) amplification has been implicated in the malignant, treatment-evasive nature of aggressive, high-risk neuroblastoma...
January 4, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29327726/generation-of-knock-in-cynomolgus-monkey-via-crispr-cas9-editing
#14
Xuan Yao, Zhen Liu, Xing Wang, Yan Wang, Yan-Hong Nie, Liang Lai, Ruilin Sun, Linyu Shi, Qiang Sun, Hui Yang
No abstract text is available yet for this article.
January 12, 2018: Cell Research
https://www.readbyqxmd.com/read/29327641/generation-of-an-arrayed-crispr-cas9-library-targeting-epigenetic-regulators-from-high-content-screens-to-in-vivo-assays
#15
Tristan Henser-Brownhill, Josep Monserrat, Paola Scaffidi
The CRISPR-Cas9 system has revolutionized genome engineering, allowing precise modification of DNA in various organisms. The most popular method for conducting CRISPR-based functional screens involves the use of pooled lentiviral libraries in selection screens coupled with next-generation sequencing. Screens employing genome-scale pooled small guide RNA (sgRNA) libraries are demanding, particularly when complex assays are used. Furthermore, pooled libraries are not suitable for microscopy-based high-content screens or for systematic interrogation of protein function...
January 12, 2018: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29327301/lncrna-gas8-as1-inhibits-cell-proliferation-through-atg5-mediated-autophagy-in-papillary-thyroid-cancer
#16
Yuan Qin, Wei Sun, Hao Zhang, Ping Zhang, Zhihong Wang, Wenwu Dong, Liang He, Ting Zhang, Liang Shao, Wenqian Zhang, Changhao Wu
PURPOSE: The long non-coding RNA GAS8 antisense RNA 1 (lncRNA GAS8-AS1) is a tumor suppressor in papillary thyroid cancer (PTC), but the mechanisms underlying how GAS8-AS1 regulates PTC biology remain unclear. Here, we evaluated the molecular function of GAS8-AS1 in regulating autophagy in PTC cell lines. METHODS: GAS8-AS1 was overexpressed and knocked down in PTC cell lines by transfecting with expression plasmids or short interfering RNAs (siRNAs). Cell proliferation was evaluated using the Cell Counting Kit-8 (CCK-8)...
January 11, 2018: Endocrine
https://www.readbyqxmd.com/read/29327155/downregulation-of-mir-503-contributes-to-the-development-of-drug-resistance-in-ovarian-cancer-by-targeting-pi3k-p85
#17
Di Wu, Pan Lu, Xue Mi, Jinwei Miao
OBJECTIVE: Cisplatin is an important chemotherapeutic agent frequently used in the treatment of ovarian cancer. However, resistance to cisplatin is an obstacle to the treatment of ovarian cancer. Recently, many studies have demonstrated that microRNAs (miRNAs) are involved in the drug resistance of ovarian cancer cells. In this study, we explored the role of miR-503 in cisplatin-resistant ovarian cancer. MATERIALS AND METHODS: To investigate the relationship between miR-503 expression and the sensitivity of ovarian cancer cells to cisplatin, the cells were transfected with miR-503 mimics/inhibitors...
January 11, 2018: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/29327067/overexpression-of-nogo-receptor-3-ngr3-correlates-with-poor-prognosis-and-contributes-to-the-migration-of-epithelial-cells-of-nasopharyngeal-carcinoma-patients
#18
Jiang-Yi He, Ping Han, Yu Zhang, Yong-Dong Liu, Shi-Jian Song, Guo-Kai Feng, Yu An, Ai-Jun Zhou, Hong-Bo Wang, Li Yuan, Zhi-Rui Lin, Tian-Liang Xia, Man-Zhi Li, Yan-Min Liu, Xiao-Ming Huang, Hua Zhang, Qian Zhong
Lymph node metastasis (N classification) is one of the most important prognostic factors of nasopharyngeal carcinoma (NPC), and nerve involvement is associated with the transition of the N category in NPC patients. Although the nervous system has been reported to participate in many types of cancer progression, its functions in NPC progression remains unknown. Through analysis of gene profiling data, we demonstrate an enrichment of genes associated with neuronal development and differentiation in NPC tissues and cell lines...
January 11, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29325990/quantitative-proteomics-reveals-a-role-of-jaz7-in-plant-defense-response-to-pseudomonas-syringae-dc3000
#19
Tong Zhang, Li Meng, Wenwen Kong, Zepeng Yin, Yang Wang, Jacqueline D Schneider, Sixue Chen
Jasmonate ZIM-domain (JAZ) proteins are key transcriptional repressors regulating various biological processes. Although many studies have studied JAZ proteins by genetic and biochemical analyses, little is known about JAZ7-associated global protein networks and how JAZ7 contributes to bacterial pathogen defense. In this study, we aim to fill this knowledge gap by conducting unbiased large-scale quantitative proteomics using tandem mass tags (TMT). We compared the proteomes of a JAZ7 knock-out line, a JAZ7 overexpression line, as well as the wild type Arabidopsis plants in the presence and absence of Pseudomonas syringae DC3000 infection...
January 8, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29325778/nonstructural-proteins-nsp2tf-and-nsp2n-of-porcine-reproductive-and-respiratory-syndrome-virus-prrsv-play-important-roles-in-suppressing-host-innate-immune-responses
#20
Y Li, P Shang, D Shyu, C Carrillo, P Naraghi-Arani, Crystal J Jaing, G J Renukaradhya, A E Firth, E J Snijder, Y Fang
Recently, we identified a unique -2/-1 ribosomal frameshift mechanism in PRRSV, which yields two truncated forms of nonstructural protein (nsp) 2 variants, nsp2TF and nsp2N. Here, in vitro expression of individual PRRSV nsp2TF and nsp2N demonstrated their ability to suppress cellular innate immune responses in transfected cells. Two recombinant viruses were further analyzed, in which either nsp2TF was C-terminally truncated (vKO1) or expression of both nsp2TF and nsp2N was knocked out (vKO2). Host cellular mRNA profiling showed that a panel of cellular immune genes, in particular those involved in innate immunity, was upregulated in cells infected with vKO1 and vKO2...
January 8, 2018: Virology
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