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https://www.readbyqxmd.com/read/28935812/mir-130a-deregulates-pten-and-stimulates-tumor-growth
#1
Huijun Wei, Ri Cui, Julian Bahr, Nicola Zanesi, Zhenghua Luo, Wei Meng, Guang Liang, Carlo M Croce
H-RasV12 oncogene has been shown to promote autophagic cell death. Here we provide evidence of a contextual role for H-RasV12 in cell death that is varied by its effects on miR-130a. In E1A-immortalized murine embryo fibroblasts, acute expression of H-RasV12 promoted apoptosis but not autophagic cell death. miRNA screens in this system showed that miR-130a was strongly downregulated by H-RasV12 in this model system. Enforced expression of miR-130a increased cell proliferation in part via repression of PTEN...
September 21, 2017: Cancer Research
https://www.readbyqxmd.com/read/28929492/potent-antitumor-effect-of-tumor-microenvironment-targeted-oncolytic-adenovirus-against-desmoplastic-pancreatic-cancer
#2
Yan Li, JinWoo Hong, Joung-Eun Oh, A-Rum Yoon, Chae-Ok Yun
Pancreatic cancer is a leading cause of cancer-related death. Desmoplastic pancreatic tumors exhibit excessive extracellular matrix (ECM) and are thus highly resistant to anticancer therapeutics, since the ECM restricts drug penetration and dispersion. Here, we designed and generated two hypoxia-responsive and cancer-specific hybrid promoters, H(mT)E and H(E)mT. Transgene expression driven by each hybrid promoter was markedly higher under hypoxic conditions than normoxic conditions. Moreover, H(E)mT-driven transgene expression was highly cancer-specific and was superior to that of H(mT)E-driven expression...
September 20, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28918031/anti-adenoviral-artificial-micrornas-expressed-from-aav9-vectors-inhibit-human-adenovirus-infection-in-immunosuppressed-syrian-hamsters
#3
Katrin Schaar, Anja Geisler, Milena Kraus, Sandra Pinkert, Markian Pryshliak, Jacqueline F Spencer, Ann E Tollefson, Baoling Ying, Jens Kurreck, William S Wold, Robert Klopfleisch, Karoly Toth, Henry Fechner
Infections of immunocompromised patients with human adenoviruses (hAd) can develop into life-threatening conditions, whereas drugs with anti-adenoviral efficiency are not clinically approved and have limited efficacy. Small double-stranded RNAs that induce RNAi represent a new class of promising anti-adenoviral therapeutics. However, as yet, their efficiency to treat hAd5 infections has only been investigated in vitro. In this study, we analyzed artificial microRNAs (amiRs) delivered by self-complementary adeno-associated virus (scAAV) vectors for treatment of hAd5 infections in immunosuppressed Syrian hamsters...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28885709/prenylation-of-viral-proteins-by-enzymes-of-the-host-virus-driven-rationale-for-therapy-with-statins-and-ft-ggt1-inhibitors
#4
REVIEW
Ekaterina S Marakasova, Birgit Eisenhaber, Sebastian Maurer-Stroh, Frank Eisenhaber, Ancha Baranova
Intracellular bacteria were recently shown to employ eukaryotic prenylation system for modifying activity and ensuring proper intracellular localization of their own proteins. Following the same logic, the proteins of viruses may also serve as prenylation substrates. Using extensively validated high-confidence prenylation predictions by PrePS with a cut-off for experimentally confirmed farnesylation of hepatitis delta virus antigen, we compiled in silico evidence for several new prenylation candidates, including IRL9 (CMV) and few other proteins encoded by Herpesviridae, Nef (HIV-1), E1A (human adenovirus 1), NS5A (HCV), PB2 (influenza), HN (human parainfluenza virus 3), L83L (African swine fever), MC155R (molluscum contagiosum virus), other Poxviridae proteins, and some bacteriophages of human associated bacteria...
September 8, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28874135/cytotoxicity-of-replication-competent-adenoviruses-powered-by-an-exogenous-regulatory-region-is-not-linearly-correlated-with-the-viral-infectivity-gene-expression-or-with-the-e1a-activating-ability-but-is-associated-with-the-p53-genotypes
#5
Suguru Yamauchi, Boya Zhong, Kiyoko Kawamura, Shan Yang, Shuji Kubo, Masato Shingyoji, Ikuo Sekine, Yuji Tada, Koichiro Tatsumi, Hideaki Shimada, Kenzo Hiroshima, Masatoshi Tagawa
BACKGROUND: Replication-competent adenoviruses (Ad) produced cytotoxic effects on infected tumors and have been examined for the clinical applicability. A biomarkers to predict the cytotoxicity is valuable in a clinical setting. METHODS: We constructed type 5 Ad (Ad5) of which the expression of E1A gene was activated by a 5' regulatory sequences of survivin, midkine or cyclooxygenase-2, which were highly expressed in human tumors. We also produced the same replication-competent Ad of which the fiber-knob region was replaced by that of Ad35 (AdF35)...
September 5, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28867494/targeting-human-breast-cancer-cells-by-an-oncolytic-adenovirus-using-microrna-targeting-strategy
#6
Mohammad Shayestehpour, Sharareh Moghim, Vahid Salimi, Somayeh Jalilvand, Jila Yavarian, Bizhan Romani, Talat Mokhtari-Azad
MicroRNA-targeting strategy is a promising approach that enables oncolytic viruses to replicate in tumor cells but not in normal cells. In this study, we targeted adenoviral replication toward breast cancer cells by inserting ten complementary binding sites for miR-145-5p downstream of E1A gene. In addition, we evaluated the effect of increasing miR-145 binding sites on inhibition of virus replication. Ad5-control and adenoviruses carrying five or ten copies of miR145-5p target sites (Ad5-5miR145T, Ad5-10miR145T) were generated and inoculated into MDA-MB-453, BT-20, MCF-7 breast cancer cell lines and human mammary epithelial cells (HMEpC)...
September 1, 2017: Virus Research
https://www.readbyqxmd.com/read/28796161/comparison-of-liver-detargeting-strategies-for-systemic-therapy-with-oncolytic-adenovirus-serotype-5
#7
Tien V Nguyen, Mary E Barry, Mallory A Turner, Catherine M Crosby, Miguel A Trujillo, John C Morris, Michael A Barry
Oncolytic viruses would ideally be of use for systemic therapy to treat disseminated cancer. To do this safely, this may require multiple layers of cancer specificity. The pharmacology and specificity of oncolytic adenoviruses can be modified by (1) physical retargeting, (2) physical detargeting, (3) chemical shielding, or (4) by modifying the ability of viral early gene products to selectively activate in cancer versus normal cells. We explored the utility of these approaches with oncolytic adenovirus serotype 5 (Ad5) in immunocompetent Syrian hamsters bearing subcutaneous HaK tumors...
August 10, 2017: Biomedicines
https://www.readbyqxmd.com/read/28789701/a-novel-bladder-cancer-specific-oncolytic-adenovirus-by-cd46-and-its-effect-combined-with-cisplatin-against-cancer-cells-of-car-negative-expression
#8
Wenjuan Cao, Junqiang Tian, Chong Li, Yanjun Gao, Xingchen Liu, Jianzhong Lu, Yuhan Wang, Zhiping Wang, Robert S Svatek, Ronald Rodriguez
BACKGROUND: Conditionally replicative oncolytic adenoviruses (CRAds) display significant anti-tumor effects. However, the traditional adenovirus of serotype 5 (Ad5) entering cancer cells via coxsackie virus and adenovirus receptor (CAR) can't be utilized for bladder cancer with low expression of CAR, which limits the application of Ad5. METHODS: We utilized Ad5/F11p containing the chimeric fiber gene encoding the Ad5 fiber tail domain and Ad11p fiber shaft and knob domains to construct bladder cancer-specific chimeric type viruses Ad5/F11p-PSCAE-UPII-E1A, which can infect bladder cancer cells mediated by CD46 molecule...
August 8, 2017: Virology Journal
https://www.readbyqxmd.com/read/28752543/exonal-switch-down-regulates-the-expression-of-cd5-on-blasts-of-acute-t-cell-leukemia
#9
Ambak Kumar Rai, Amar Singh, Ankit Saxena, Tulika Seth, Vinod Raina, Dipendra Kumar Mitra
CD5 expression and its role in acute T cell lymphoblastic leukemia (T-ALL) have not been elaborately studied so far. We observed a significant reduction in surface expression of CD5 (sCD5) on leukemic T cells compared to autologous non-leukemic T cells. In this study, we have shown the molecular mechanism regulating the expression and function of CD5 on leukemic T cells. Total 250 numbers of patients suffering from leukemia and lymphoma were immunophenotyped. Final diagnosis was based on their clinical presentation, morphological data and flowcytometry based immunophenotyping...
July 28, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28706153/inhibitor-of-growth-protein-4-interacts-with-beclin-1-and-represses-autophagy
#10
Valentina Sica, José Manuel Bravo-San Pedro, Guo Chen, Guillermo Mariño, Sylvie Lachkar, Valentina Izzo, Maria Chiara Maiuri, Mireia Niso-Santano, Guido Kroemer
Beclin 1 (BECN1) is a multifunctional protein that activates the pro-autophagic class III phosphatidylinositol 3-kinase (PIK3C3, best known as VPS34), yet also interacts with multiple negative regulators. Here we report that BECN1 interacts with inhibitor of growth family member 4 (ING4), a tumor suppressor protein that is best known for its capacity to interact with the tumor suppressor protein p53 (TP53) and the acetyltransferase E1A binding protein p300 (EP300). Removal of TP53 or EP300 did not affect the BECN1/ING4 interaction, which however was lost upon culture of cells in autophagy-inducing, nutrient free conditions...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28698142/a-novel-oncolytic-adenovirus-targeting-wnt-signaling-effectively-inhibits-cancer-stem-like-cell-growth-via-metastasis-apoptosis-and-autophagy-in-hcc-models
#11
Jian Zhang, Weijie Lai, Qiang Li, Yang Yu, Jin Jin, Wan Guo, Xiumei Zhou, Xinyuan Liu, Yigang Wang
Cancer stem cells (CSCs), which are highly differentiated and self-renewing, play an important role in the occurrence, therapeutic resistant and metastasis of hepatacellular carcinoma (HCC). Oncolytic adenoviruses have targeted killing effect on tumor cells, and are invoked as candidate drugs for cancer treatment. We designed a dual-regulated oncolytic adenovirus Ad.wnt-E1A(△24bp)-TSLC1 that targets Wnt and Rb signaling pathways respectively, and carries the tumor suppressor gene, TSLC1. Previous studies have demonstrated that oncolytic adenovirus mediated TSLC1can target liver cancer and exhibit significant cytotoxicity...
September 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28651743/the-combination-of-nk-and-cd8-t-cells-with-ccl20-il15-armed-oncolytic-adenoviruses-enhances-the-growth-suppression-of-tert-positive-tumor-cells
#12
Jun-Feng Ye, Wen-Xi Qi, Ming-Yuan Liu, Yang Li
Adoptive immunotherapy and targeted gene therapy have been extensively used to eliminate tumor cells. The combination treatment is capable of efficiently generating an effective antitumor immune response and disrupting tumor-induced tolerance. Moreover, effective antitumor immune responses are dependent on coordinate interaction among various effector cells. This study focused on whether the combination of cytotoxic effector cell-based adoptive immunotherapy and CCL20/IL15-armed oncolytic adenoviruses could induce enhanced antitumor activity...
August 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28643325/surface-expression-of-anti-cd3scfv-stimulates-locoregional-immunotherapy-against-hepatocellular-carcinoma-depending-on-the-e1a-engineered-human-umbilical-cord-mesenchymal-stem-cells
#13
Qing Zhang, Xiang-Fei Yuan, Yang Lu, Zhen-Zhen Li, Shi-Qi Bao, Xiao-Long Zhang, Yuan-Yuan Yang, Dong-Mei Fan, Yi-Zhi Zhang, Chen-Xuan Wu, Hong-Xing Guo, Yan-Jun Zhang, Zhou Ye, Dong-Sheng Xiong
Tumor antigens is at the core of cancer immunotherapy, however, the ideal antigen selection is difficult especially in poorly immunogenic tumors. In this study, we designed a strategy to modify hepatocellular carcinoma (HCC) cells by surface expressing anti-CD3scfv within the tumor site strictly, which depended on the E1A-engineered human umbilical cord mesenchymal stem cells (HUMSC.E1A) delivery system. Subsequently, membrane-bound anti-CD3scfv actived the lymphocytes which lysed HCC cells bypassing the expression of antigens or MHC restriction...
October 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28588706/il-17a-promotes-the-proliferation-of-human-nasopharyngeal-carcinoma-cells-through-p300-mediated-akt1-acetylation
#14
Kemin Cai, Bing Wang, Hongmei Dou, Ronglan Luan, Xueli Bao, Jiusheng Chu
Interleukin (IL)-17A is a T helper (Th)17 cell-secreted cytokine that is able to induce various inflammatory responses. There is emerging evidence that IL-17A is generated in the cancer microenvironment of human nasopharyngeal carcinoma (NPC). However, the role of IL-17A in NPC remains unclear. Thus, the present study aimed to examine the direct influence of IL-17A stimulation on the proliferation of human NPC cells and identify the underlying molecular mechanisms. Furthermore, E1A binding protein p300 (p300)-mediated AKT serine/threonine kinase 1 (Akt1) acetylation and its role in regulating the proliferation of NPC cells was investigated...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28586030/expression-of-the-ep300-tp53-and-bax-genes-in-colorectal-cancer-correlations-with-clinicopathological-parameters-and-survival
#15
Anna E Kowalczyk, Bartlomiej E Krazinski, Janusz Godlewski, Jolanta Kiewisz, Przemyslaw Kwiatkowski, Agnieszka Sliwinska-Jewsiewicka, Jacek Kiezun, Marian Sulik, Zbigniew Kmiec
E1A binding protein P300 (EP300), tumor protein P53 (TP53) and BCL2 associated X, apoptosis regulator (BAX) genes encode proteins which cooperate to regulate important cellular processes. The present study aimed to determine the expression levels of EP300, TP53 and BAX in colorectal cancer (CRC) and to investigate their prognostic value and association with the progression of CRC. Tumor and matched unchanged colorectal tissues were collected from 121 CRC patients. Quantitative polymerase chain reaction and immunohistochemistry were used to assess the mRNA and protein levels of the studied genes...
July 2017: Oncology Reports
https://www.readbyqxmd.com/read/28551630/expression-and-prognostic-significance-of-ep300-tp53-and-bax-in-clear-cell-renal-cell-carcinoma
#16
Janusz Godlewski, Bartlomiej E Krazinski, Anna E Kowalczyk, Jolanta Kiewisz, Jacek Kiezun, Przemyslaw Kwiatkowski, Agnieszka Sliwińska-Jewsiewicka, Piotr W Wierzbicki, Zbigniew Kmieć
BACKGROUND: Histone acetyltransferase E1A-binding protein p300 (EP300), tumor protein p53 (TP53) and B-cell lymphoma-2-associated X protein (BAX) contribute to the regulation of the cell cycle and apoptosis, cellular processes that are often impaired in cancer cells. The aim of this study was to determine the expression levels of EP300, TP53 and BAX genes and their respective proteins in clear cell renal cell carcinoma (ccRCC) and evaluate the value of these factors as prognostic factors...
June 2017: Anticancer Research
https://www.readbyqxmd.com/read/28508477/the-novel-intracellular-protein-creg-inhibits-hepatic-steatosis-obesity-and-insulin-resistance
#17
Quan-Yu Zhang, Ling-Ping Zhao, Xiao-Xiang Tian, Cheng-Hui Yan, Yang Li, Yan-Xia Liu, Pi-Xiao Wang, Xiao-Jing Zhang, Ya-Ling Han
Cellular repressor of E1A-stimulated genes (CREG), a novel cellular glycoprotein, has been identified as a suppressor of various cardiovascular diseases because of its capacity to reduce hyperplasia, maintain vascular homeostasis, and promote endothelial restoration. However, the effects and mechanism of CREG in metabolic disorder and hepatic steatosis remain unknown. Here, we report that hepatocyte-specific CREG deletion dramatically exacerbates high-fat diet and leptin deficiency-induced (ob/ob) adverse effects such as obesity, hepatic steatosis, and metabolic disorders, whereas a beneficial effect is conferred by CREG overexpression...
May 15, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28484034/modeling-the-response-of-a-tumor-suppressive-network-to-mitogenic-and-oncogenic-signals
#18
Xinyu Tian, Bo Huang, Xiao-Peng Zhang, Mingyang Lu, Feng Liu, José N Onuchic, Wei Wang
Intrinsic tumor-suppressive mechanisms protect normal cells against aberrant proliferation. Although cellular signaling pathways engaged in tumor repression have been largely identified, how they are orchestrated to fulfill their function still remains elusive. Here, we built a tumor-suppressive network model composed of three modules responsible for the regulation of cell proliferation, activation of p53, and induction of apoptosis. Numerical simulations show a rich repertoire of network dynamics when normal cells are subject to serum stimulation and adenovirus E1A overexpression...
May 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28463838/engineering-the-rapid-adenovirus-production-and-amplification-rapa-cell-line-to-expedite-the-generation-of-recombinant-adenoviruses
#19
Qiang Wei, Jiaming Fan, Junyi Liao, Yulong Zou, Dongzhe Song, Jianxiang Liu, Jing Cui, Feng Liu, Chao Ma, Xue Hu, Li Li, Yichun Yu, Xiangyang Qu, Liqun Chen, Xinyi Yu, Zhicai Zhang, Chen Zhao, Zongyue Zeng, Ruyi Zhang, Shujuan Yan, Xingye Wu, Yi Shu, Russell R Reid, Michael J Lee, Jennifer Moritis Wolf, Tong-Chuan He
BACKGROUND/AIMS: While recombinant adenoviruses are among the most widely-used gene delivery vectors and usually propagated in HEK-293 cells, generating recombinant adenoviruses remains time-consuming and labor-intense. We sought to develop a rapid adenovirus production and amplification (RAPA) line by assessing human Ad5 genes (E1A, E1B19K/55K, pTP, DBP, and DNA Pol) and OCT1 for their contributions to adenovirus production. METHODS: Stable transgene expression in 293T cells was accomplished by using piggyBac system...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28460470/a-novel-oncolytic-adenovirus-based-on-simian-adenovirus-serotype-24
#20
Tao Cheng, Yufeng Song, Yan Zhang, Chao Zhang, Jieyun Yin, Yudan Chi, Dongming Zhou
Among the oncolytic virotherapy, an emerging treatment for tumor, adenoviruses are widely used at present in preclinical and clinical trials. Traditionally, oncolytic adenoviruses were developed based on the human adenovirus serotype 5 (AdHu5). However, AdHu5 has the drawbacks of preexisting anti-AdHu5 immunity in most populations, and extensive sequestration of Adhu5 by the liver through hexon, blood coagulation factor X (FX), and FX receptor interactions. To tackle these problems, we explored a novel oncolytic adenovirus AdC7-SP/E1A-ΔE3 for cancer treatment...
April 18, 2017: Oncotarget
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