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Oncolytic viral therapy

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https://www.readbyqxmd.com/read/29449555/intravenous-injections-of-the-oncolytic-virus-m1-as-a-novel-therapy-for-muscle-invasive-bladder-cancer
#1
Cheng Hu, Ying Liu, Yuan Lin, Jian-Kai Liang, Wen-Wen Zhong, Ke Li, Wen-Tao Huang, De-Juan Wang, Guang-Mei Yan, Wen-Bo Zhu, Jian-Guang Qiu, Xin Gao
Muscle-invasive bladder cancer (MIBC) is associated with low survival and high recurrence rates even in cases in which patients receive systemic treatments, such as surgery and chemotherapy. Here, we found that a naturally existing alphavirus, namely, M1, selectively kills bladder cancer cells but not normal cells, findings supported by our observations of changes in viral replication and MIBC and patient-derived MIBC cell apoptosis. Transcriptome analysis revealed that interferon-stimulated genes (ISGs) are expressed at low levels in sensitive bladder cancer cells and high levels in resistant cells...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29441069/interleukin-6-and-interferon-%C3%AE-signaling-via-jak1-stat-differentially-regulate-oncolytic-versus-cytoprotective-antiviral-states
#2
Oded Danziger, Tal Pupko, Eran Bacharach, Marcelo Ehrlich
Malignancy-induced alterations to cytokine signaling in tumor cells differentially regulate their interactions with the immune system and oncolytic viruses. The abundance of inflammatory cytokines in the tumor microenvironment suggests that such signaling plays key roles in tumor development and therapy efficacy. The JAK-STAT axis transduces signals of interleukin-6 (IL-6) and interferons (IFNs), mediates antiviral responses, and is frequently altered in prostate cancer (PCa) cells. However, how activation of JAK-STAT signaling with different cytokines regulates interactions between oncolytic viruses and PCa cells is not known...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29438228/antitumor-effect-of-the-newcastle-disease-viral-hemagglutinin-neuraminidase-gene-is-expressed-through-an-oncolytic-adenovirus-effect-in-osteosarcoma-cells
#3
Shuang Chen, Qinggao Zhang, Duo Xu, Yiquan Li, Yuanyuan Fan, Wenjie Li, Xunzhe Yin, Yang Zhang, Jingwei Liu, Xiao Li, Lili Sun, Ningyi Jin
Newcastle disease virus (NDV) can specifically kill cancer cells and has less toxicity to normal cells. The hemagglutinin-neuraminidase (HN) protein is an important structural protein in NDV pathogenesis and has been postulated as a promising candidate for antitumor therapy. The aim of this study was to investigate the anticancer potential of recombinant adenovirus Ad-HN-PEG3p-E1a. An MTS assay was performed to determine viral proliferation after viral infection, the data showed that the proliferation ability of osteosarcoma cells decreased, whereas there was no significant change in normal hepatic cells...
March 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29435080/a-novel-approach-to-glioma-therapy-using-an-oncolytic-adenovirus-with-two-specific-promoters
#4
Feng Liu, Kaya Xu, Hua Yang, Yuming Li, Jian Liu, Jixiang Wang, Zhizhong Guan
Gliomas are the most common type of primary brain tumor in adults, where more than half of the cases are malignant, and the prognosis is poor. The early viral 1A (E1A) protein has been widely recognized to be essential for adenoviral replication and production of progeny virions in human cells, a process that is regulated by human telomerase reverse transcriptase. The p53 gene, as a tumor suppressor, regulates diverse cellular processes, including cell cycle arrest, cell autophagy, senescence and apoptosis...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29420595/combination-therapy-for-cancer-with-oncolytic-virus-and-checkpoint-inhibitor-a-mathematical-model
#5
Avner Friedman, Xiulan Lai
Oncolytic virus (OV) is a replication competent virus that selectively invades cancer cells; as these cells die under the viral burden, the released virus particles proceed to infect other cancer cells. Oncolytic viruses are designed to also be able to stimulate the anticancer immune response. Thus, one may represent an OV by two parameters: its replication potential and its immunogenicity. In this paper we consider a combination therapy with OV and a checkpoint inhibitor, anti-PD-1. We evaluate the efficacy of the combination therapy in terms of the tumor volume at some later time, for example, 6 months from initial treatment...
2018: PloS One
https://www.readbyqxmd.com/read/29417403/implementing-a-program-of-talimogene-laherparepvec
#6
Frances Collichio, Lauren Burke, Amber Proctor, Diana Wallack, Anthony Collichio, Patricia K Long, David W Ollila
BACKGROUND: Oncolytic viruses are genetically engineered or naturally occurring viruses that selectively replicate in cancer cells without harming normal cells. Talimogene laherparepvec (Imlygic®), the first oncolytic viral therapy approved for treatment of cancer, was approved for treatment of locally advanced melanoma in October 2015. PURPOSE: As a biologic product, use of T. laherparepvec in the clinical setting requires pretreatment planning and a unique systematic approach to deliver the therapy...
February 7, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29399179/antitumor-and-immunostimulatory-activities-of-a-genotype-v-recombinant-attenuated-veterinary-newcastle-disease-virus-vaccine
#7
Oscar Antonio Ortega-Rivera, J Luis Quintanar, Susana Del Toro-Arreola, Ángel G Alpuche-Solis, Mayra J Esparza-Araiza, Eva Salinas
Antitumor conventional treatments including chemo/radiotherapy result in several side effects and non-specificity. Therapies including the use of oncolytic viruses, particularly the Newcastle disease virus (NDV), have emerged as an attractive alternative due to their capacity to kill cancer cells directly or through stimulation of the immune system. In the present study, a commercial vaccine composed of a recombinant attenuated NDV strain P05 (rNDV-P05) was assessed for antitumor and immunostimulatory activity...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29367943/using-cystine-knot-proteins-as-a-novel-approach-to-retarget-oncolytic-measles-virus
#8
Sangeet Lal, Corey Raffel
Modified measles virus (MV) has effective oncolytic activity preclinically and is currently being investigated in clinical trials for various types of cancer. We investigated the use of cystine knot proteins (CKPs) to direct MV activity. CKPs are short polypeptides that bind their targets with high affinity. We used a CKP that binds αvβ3, αvβ5, and α5β1 integrins with single-digit nanomolar affinity to retarget MV to the integrins (MV-CKPint). MV-CKPint infected, replicated in, and killed human glioblastoma, medulloblastoma, diffuse intrinsic pontine glioma (DIPG), and melanoma cancer cells in vitro, all of which express the target integrins...
December 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/29362367/a-hypoxia-and-telomerase-responsive-oncolytic-adenovirus-expressing-secretable-trimeric-trail-triggers-tumour-specific-apoptosis-and-promotes-viral-dispersion-in-trail-resistant-glioblastoma
#9
Eonju Oh, JinWoo Hong, Oh-Joon Kwon, Chae-Ok Yun
Glioblastoma is a highly aggressive and malignant type of cancer that is apoptosis resistant and difficult to cure by conventional cancer therapies. In this regard, an oncolytic adenovirus that selectively targets the tumour tissue and induces tumour cell lysis is a promising treatment option. We designed and constructed a hypoxia-responsive and cancer-specific modified human telomerase reverse transcriptase (H5CmTERT) promoter to drive replication of an oncolytic adenovirus (H5CmTERT-Ad). To enhance the anti-tumour efficacy of H5CmTERT-Ad against malignant glioblastoma, we also generated an H5CmTERT-Ad expressing secretable trimeric tumour necrosis factor-related apoptosis-inducing ligand (H5CmTERT-Ad/TRAIL)...
January 23, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343567/parainfluenza-virus-infection-sensitizes-cancer-cells-to-dna-damaging-agents-implications-for-oncolytic-virus-therapy
#10
Candace R Fox, Griffith D Parks
We have previously shown that the Parainfluenza virus 5 (PIV5) mutant P/V-CPI- is restricted for spread in normal cells but not in cancer cells in vitro and is effective at reducing tumor burden in mouse model systems. Here we show that P/V-CPI- infection of human laryngeal cancer HEp-2 cells results in the majority of the cells dying, but unexpectedly, over time there is an emergence of a population of cells which survive as P/V-CPI- persistently infected (PI) cells. P/V-CPI- PI cells had elevated levels of basal caspase activation, and viability was highly dependent on activity of cellular inhibitors of apoptosis (IAPs) such as Survivin and XIAP...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29327081/neutrophils-in-viral-infection
#11
REVIEW
Victor Naumenko, Madison Turk, Craig N Jenne, Seok-Joo Kim
Neutrophils are the first wave of recruited immune cells to sites of injury or infection and are crucial players in controlling bacterial and fungal infections. Although the role of neutrophils during bacterial or fungal infections is well understood, their impact on antiviral immunity is much less studied. Furthermore, neutrophil function in tumor pathogenesis and cancer treatment has recently received much attention, particularly within the context of oncolytic virus infection where neutrophils produce antitumor cytokines and enhance oncolysis...
January 11, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29275471/oncolytic-virotherapy-and-the-tumor-microenvironment
#12
Sara E Berkey, Steve H Thorne, David L Bartlett
Oncolytic viral therapy is a promising approach to treat many malignancies, including breast, colorectal, hepatocellular, and melanoma. The best results are seen when using "targeted and armed" viruses. These are viruses that have been genetically modified to selectively replicate within cancer cells and express specific transgenes that alter the tumor microenvironment to inhibit tumor progression. The products of these transgenes induce cell death, make the virus less virulent, compromise tumor vascularity, and are capable of modulating or enhancing the immune system-such as cytokines and chemokines...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29275092/antitumor-benefits-of-antiviral-immunity-an-underappreciated-aspect-of-oncolytic-virotherapies
#13
REVIEW
Shashi Gujar, Jonathan G Pol, Youra Kim, Patrick W Lee, Guido Kroemer
Oncolytic viruses (OVs) represent a new class of cancer immunotherapeutics. Administration of OVs to cancer-bearing hosts induces two distinct immunities: antiviral and antitumor. While antitumor immunity is beneficial, antiviral immune responses are often considered detrimental for the efficacy of OV-based therapy. The existing dogma postulates that anti-OV immune responses restrict viral replication and spread, and thus reduce direct OV-mediated killing of cancer cells. Accordingly, a myriad of therapeutic strategies aimed at mitigating anti-OV immune responses is presently being tested...
December 20, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/29259007/amplification-of-oncolytic-vaccinia-virus-widespread-tumor-cell-killing-by-sunitinib-through-multiple-mechanisms
#14
Minah Kim, Maximilian Nitschké, Barbara Sennino, Patrizia Murer, Brian J Schriver, Alexander M Bell, Aishwarya Subramanian, Corry E McDonald, Jiahu Wang, Howard Cha, Marie-Claude Bourgeois-Daigneault, David H Kirn, John C Bell, Naomi De Silva, Caroline J Breitbach, Donald M McDonald
Oncolytic viruses pose many questions in their use in cancer therapy. In this study, we assessed the potential of mpJX-594 (mouse-prototype JX-594), a replication-competent vaccinia virus administered by intravenous injection, to target the tumor vasculature, produce immune activation and tumor cell killing more widespread than the infection, and suppress invasion and metastasis. These actions were examined in RIP-Tag2 transgenic mice with pancreatic neuroendocrine tumors (PNET) that developed spontaneously and progress as in humans...
December 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/29228615/combined-therapy-of-colon-carcinomas-with-an-oncolytic-adenovirus-and-valproic-acid
#15
Christian Bressy, Dragomira Majhen, Najat Raddi, Wael Jdey, Gaétan Cornilleau, Léna Zig, Josée Guirouilh-Barbat, Bernard S Lopez, Olivia Bawa, Paule Opolon, Elodie Grellier, Karim Benihoud
The anti-tumor potential of oncolytic adenoviruses (CRAds) has been demonstrated in preclinical and clinical studies. While these agents failed to eradicate tumors when used as a monotherapy, they may be more effective if combined with conventional treatments such as radiotherapy or chemotherapy. This study seeks to evaluate the combination of a CRAd bearing a ∆24 deletion in E1A with valproic acid (VPA), a histone deacetylase inhibitor, for the treatment of human colon carcinomas. This combination led to a strong inhibition of cell growth both in vitro and in vivo compared to treatment with CRAd or VPA alone...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29216507/chimeric-hcmv-hsv-1-and-%C3%AE-%C3%AE-134-5-oncolytic-herpes-simplex-virus-elicit-immune-mediated-antigliomal-effect-and-antitumor-memory
#16
Mohammed G Ghonime, Josh Jackson, Amish Shah, Justin Roth, Mao Li, Ute Saunders, Jennifer Coleman, G Yancey Gillespie, James M Markert, Kevin A Cassady
Malignant gliomas are the most common primary brain tumor and are characterized by rapid and highly invasive growth. Because of their poor prognosis, new therapeutic strategies are needed. Oncolytic virotherapy (OV) is a promising strategy for treating cancer that incorporates both direct viral replication mediated and immune mediated mechanisms to kill tumor cells. C134 is a next generation Δγ134.5 oHSV-1 with improved intratumoral viral replication. It remains safe in the CNS environment by inducing early IFN signaling which restricts its replication in non-malignant cells...
December 4, 2017: Translational Oncology
https://www.readbyqxmd.com/read/29200874/simultaneous-overexpression-of-mir-126-and-mir-34a-induces-a-superior-antitumor-efficacy-in-pancreatic-adenocarcinoma
#17
Shu-De Feng, Ziming Mao, Chunying Liu, Yu-Song Nie, Bin Sun, Minggao Guo, Changqing Su
Background: Pancreatic adenocarcinoma (PAC) is one of the most fatal cancers due to its high degree of malignancy, increasing incidence, high mortality, and unsatisfactory treatment efficacy. Evidence has suggested that numerous microRNAs (miRNAs), including miR-126 and miR-34a, have potent tumor-suppressing effects on PAC, implicating a possible application of miRNA in tumor therapy. However, the therapeutic effect of a single miRNA on pancreatic cancer is limited. Methods: We simultaneously delivered miR-126 and miR-34a into PAC cells by a carcinoembryonic antigen promoter-driven oncolytic adenovirus (AdCEAp-miR126/34a), and examined the antitumor efficacy of the therapeutic system in in vitro and in vivo experiments...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29179527/hitting-the-nail-on-the-head-combining-oncolytic-adenovirus-mediated-virotherapy-and-immunomodulation-for-the-treatment-of-glioma
#18
REVIEW
Wojciech K Panek, J Robert Kane, Jacob S Young, Aida Rashidi, Julius W Kim, Deepak Kanojia, Maciej S Lesniak
Glioblastoma is a highly aggressive malignant brain tumor with a poor prognosis and the median survival 14.6 months. Immunomodulatory proteins and oncolytic viruses represent two treatment approaches that have recently been developed for patients with glioblastoma that could extend patient survival and result in better treatment outcomes for patients with this disease. Together, these approaches could potentially augment the treatment efficacy and strength of these anti-tumor therapies. In addition to oncolytic activities, this combinatory approach introduces immunomodulation locally only where cancerous cells are present...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29179469/bioluminescence-imaging-of-a-tumor-selective-thymidine-kinase-defective-vaccinia-virus-guang9-strain-after-intratumoral-or-intraperitoneal-administration-in-mice
#19
Yuedi Ding, Jun Fan, Lili Deng, Ying Peng, Jue Zhang, Biao Huang
Vaccinia virus has been used as an oncolytic virus because of its capacity to preferentially infect tumors rather than normal tissues. The vaccinia Tian Tan strain, used as a vaccine against smallpox for millions of people in China, is a promising candidate for cancer therapy. In this study, we constructed an attenuated Tian Tan strain of Guang9 with a disrupted thymidine kinase gene to enhance tumor selectivity and an inserted firefly luciferase to monitor the viral distribution by in vivo bioluminescence imaging...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29169830/rapamycin-enhances-lytic-replication-of-epstein-barr-virus-in-gastric-carcinoma-cells-by-increasing-the-transcriptional-activities-of-immediate-early-lytic-promoters
#20
Man Wang, Wei Wu, Yinfeng Zhang, Guoliang Yao, Bianli Gu
Epstein-Barr virus (EBV), a human herpesvirus, is linked to both epithelial and lymphoid malignancies. Induction of EBV reactivation is a potential therapeutic strategy for EBV-associated tumors. In this study, we assessed the effects of rapamycin on EBV reactivation in gastric carcinoma cells. We found that rapamycin upregulated expression of EBV lytic proteins and increased the viral proliferation triggered by the EBV lytic inducer sodium butyrate. Reverse transcription-qPCR, luciferase activity assays, chromatin immunoprecipitation and western blotting were employed to explore the mechanism by which rapamycin promotes EBV reactivation...
November 20, 2017: Virus Research
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