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https://www.readbyqxmd.com/read/28796161/comparison-of-liver-detargeting-strategies-for-systemic-therapy-with-oncolytic-adenovirus-serotype-5
#1
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
#2
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
#3
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
#4
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
#5
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...
July 8, 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
#6
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...
June 7, 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
#7
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
#8
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
#9
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
#10
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
#11
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 (CVDs) 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 (HFD) 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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28459882/creg1-heterozygous-mice-are-susceptible-to-high-fat-diet-induced-obesity-and-insulin-resistance
#15
Xiaoxiang Tian, Chenghui Yan, Meili Liu, Quanyu Zhang, Dan Liu, Yanxia Liu, Shaohua Li, Yaling Han
Cellular repressor of E1A-stimulated genes 1 (CREG1) is a small glycoprotein whose physiological function is unknown. In cell culture studies, CREG1 promotes cellular differentiation and maturation. To elucidate its physiological functions, we deleted the Creg1 gene in mice and found that loss of CREG1 leads to early embryonic death, suggesting that it is essential for early development. In the analysis of Creg1 heterozygous mice, we unexpectedly observed that they developed obesity as they get older. In this study, we further studied this phenotype by feeding wild type (WT) and Creg1 heterozygote (Creg1+/-) mice a high fat diet (HFD) for 16 weeks...
2017: PloS One
https://www.readbyqxmd.com/read/28434229/cell-cycle-dependent-kinase-cdk9-is-a-postexposure-drug-target-against-human-adenoviruses
#16
Vibhu Prasad, Maarit Suomalainen, Silvio Hemmi, Urs F Greber
Human adenoviruses (HAdVs) infect respiratory, gastrointestinal, and urinary tracts and give rise to eye infections and epidemic keratoconjunctivitis (EKC). They persist in lymphoid tissue and cause morbidity and mortality in immunocompromised people. Treatments with significant postexposure efficacy are not available. Here, we report that inhibition of the cell cycle-dependent kinase 9 (Cdk9) by RNA interference, or the compound flavopiridol, blocked infections with HAdV-C2/5, EKC-causing HAdV-D8/37, and progeny formation in human corneal epithelial and cancer cells...
June 9, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28416454/e1a-is-an-exogenous-in%C3%A2-vivo-tumour-suppressor
#17
Francisco J Cimas, Juan L Callejas-Valera, Dolores C García-Olmo, Javier Hernández-Losa, Pedro Melgar-Rojas, María J Ruiz-Hidalgo, Raquel Pascual-Serra, Marta Ortega-Muelas, Olga Roche, Pilar Marcos, Elena Garcia-Gil, Diego M Fernandez-Aroca, Santiago Ramón Y Cajal, J Silvio Gutkind, Ricardo Sanchez-Prieto
The E1a gene from adenovirus has become a major tool in cancer research. Since the discovery of E1a, it has been proposed to be an oncogene, becoming a key element in the model of cooperation between oncogenes. However, E1a's in vivo behaviour is consistent with a tumour suppressor gene, due to the block/delay observed in different xenograft models. To clarify this interesting controversy, we have evaluated the effect of the E1a 13s isoform from adenovirus 5 in vivo. Initially, a conventional xenograft approach was performed using previously unreported HCT116 and B16-F10 cells, showing a clear anti-tumour effect regardless of the mouse's immunological background (immunosuppressed/immunocompetent)...
April 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28356939/identification-of-genes-associated-with-tongue-cancer-in-patients-with-a-history-of-tobacco-and-or-alcohol-use
#18
Yin Zhao, Dongna Fu, Chengbi Xu, Jingpu Yang, Zonggui Wang
The present study aimed to identify genes associated with tongue cancer in patients with a history of tobacco and/or alcohol use. Microarray dataset GSE42023, including 10 tissue samples of tongue cancer from patients with a history of tobacco and/or alcohol use (habit group) and 11 tissue samples of non-habit-associated tongue cancer (non-habit group), were downloaded from the Gene Expression Omnibus database. Differentially-expressed genes (DEGs) between the habit and non-habit groups were identified using the Linear Models for Microarray Data software package...
February 2017: Oncology Letters
https://www.readbyqxmd.com/read/28356341/essential-role-for-centromeric-factors-following-p53-loss-and-oncogenic-transformation
#19
Dan Filipescu, Monica Naughtin, Katrina Podsypanina, Vincent Lejour, Laurence Wilson, Zachary A Gurard-Levin, Guillermo A Orsi, Iva Simeonova, Eleonore Toufektchan, Laura D Attardi, Franck Toledo, Geneviève Almouzni
In mammals, centromere definition involves the histone variant CENP-A (centromere protein A), deposited by its chaperone, HJURP (Holliday junction recognition protein). Alterations in this process impair chromosome segregation and genome stability, which are also compromised by p53 inactivation in cancer. Here we found that CENP-A and HJURP are transcriptionally up-regulated in p53-null human tumors. Using an established mouse embryonic fibroblast (MEF) model combining p53 inactivation with E1A or HRas-V12 oncogene expression, we reproduced a similar up-regulation of HJURP and CENP-A...
March 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28300077/translational-reprogramming-in-tumour-cells-can-generate-oncoselectivity-in-viral-therapies
#20
Eneko Villanueva, Pilar Navarro, Maria Rovira-Rigau, Annarita Sibilio, Raúl Méndez, Cristina Fillat
Systemic treatment of cancer requires tumour-selective therapies that eliminate cancer cells yet preserve healthy tissues from undesired damage. Tumoral transformation is associated with profound effects in translational reprogramming of gene expression, such that tumour-specific translational regulation presents an attractive possibility for generating oncoselective therapies. We recently discovered that mRNA translational control by cytoplasmic polyadenylation element-binding proteins (CPEBs) is reactivated in cancer...
March 16, 2017: Nature Communications
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