Enhanced genomic stability of new miRNA-regulated oncolytic coxsackievirus B3.

Genetic modification of coxsackievirus B3 (CVB3) by inserting target sequences (TS) of tumor-suppressive and/or organ-selective microRNAs (miRs) into viral genome can efficiently eliminate viral pathogenesis without significant impacts on its oncolytic activity. Nonetheless, reversion mutants (loss of miR-TS inserts) were identified as early as day 35 post-injection in ∼40% immunodeficient mice. To improve the stability, here we re-engineered CVB3 by (1) replacing the same length of viral genome at the non-coding region with TS of cardiac-selective miR-1/miR-133 and pancreas-enriched miR-216/miR-375 or (2) inserting the above miR-TS into the coding region (i.

Erratum: MicroRNA Modification of Coxsackievirus B3 Decreases Its Toxicity, while Retaining Oncolytic Potency against Lung Cancer.

[This corrects the article DOI: 10.1016/j.omto.

MicroRNA Modification of Coxsackievirus B3 Decreases Its Toxicity, while Retaining Oncolytic Potency against Lung Cancer.

We recently discovered that coxsackievirus B3 (CVB3) is a potent oncolytic virus against mutant lung adenocarcinoma. Nevertheless, the evident toxicity restricts the use of wild-type (WT)-CVB3 for cancer therapy. The current study aims to engineer the CVB3 to decrease its toxicity and to extend our previous research to determine its safety and efficacy in treating / mutant small-cell lung cancer (SCLC).

Coxsackievirus Type B3 Is a Potent Oncolytic Virus against -Mutant Lung Adenocarcinoma.

mutant ( ) lung adenocarcinoma is a refractory cancer without available targeted therapy. The current study explored the possibility to develop coxsackievirus type B3 (CVB3) as an oncolytic agent for the treatment of lung adenocarcinoma. In cultured cells, we discovered that CVB3 selectively infects and lyses lung adenocarcinoma cells (A549, H2030, and H23), while sparing normal lung epithelial cells (primary, BEAS2B, HPL1D, and 1HAEo) and lung adenocarcinoma cells (HCC4006, PC9, H3255, and H1975).

MicroRNA-145 regulates oncolytic herpes simplex virus-1 for selective killing of human non-small cell lung cancer cells.

Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide, and novel treatment modalities to improve the prognosis of patients with advanced disease are highly desirable. Oncolytic virotherapy is a promising approach for the treatment of advanced NSCLC. MicroRNAs (miRNAs) may be a factor in the regulation of tumor-specific viral replication.

Transcriptional and translational dual-regulated oncolytic herpes simplex virus type 1 for targeting prostate tumors.

The aim of this project was to demonstrate that an oncolytic herpes simplex virus type 1 (HSV-1) can replicate in a tissue- and tumor-specific fashion through both transcriptional (prostate-specific promoter, ARR(2)PB) and translational (5'-untranslated regions (5'UTRs) of rFGF-2) regulation of an essential viral gene, ICP27. We generated two recombinant viruses, ARR(2)PB-ICP27 (A27) and ARR(2)PB-5'UTR-ICP27 (AU27) and tested their efficacy and toxicity both in vitro and in vivo. The ARR(2)PB promoter caused overexpression of ICP27 gene in the presence of activated androgen receptors (ARs) and increased viral replication in prostate cells.

MicroRNA regulation of oncolytic herpes simplex virus-1 for selective killing of prostate cancer cells.

Purpose: Advanced castration-resistant prostate cancer, for which there are few treatment options, remains one of the leading causes of cancer death. MicroRNAs (miRNA) have provided a new opportunity for more stringent regulation of tumor-specific viral replication. The purpose of this study was to provide a proof-of-principle that miRNA-regulated oncolytic herpes simplex virus-1 (HSV-1) virus can selectively target cancer cells with reduced toxicity to normal tissues.

20S-protopanaxadiol-induced programmed cell death in glioma cells through caspase-dependent and -independent pathways.

20S-Protopanaxadiol (1) is an aglycon metabolic derivative of the protopanaxadiol-type ginseng saponins. In the present study, 1 was used to induce cytotoxicity for two human glioma cell lines, SF188 and U87MG. For the SF188 cells, 1 activated caspases-3, -8, -7, and -9 within 3 h and induced rapid apoptosis, which could be partially inhibited by a general caspase blocker and completely abolished when the caspase blocker was used in combination with an antioxidant.

Oncolytic herpesvirus with secretable angiostatic proteins in the treatment of human lung cancer cells.

Background: The wild-type herpes simplex virus type 1 (HSV-1) has strong infectivity and cytolytic effect on almost all types of mammalian cells. Genetic engineering can now restrict this cytolysis to only malignant cells. G207 is an oncolytic HSV-1 vector developed based on this strategy.

Rh2, a compound extracted from ginseng, hypersensitizes multidrug-resistant tumor cells to chemotherapy.

Rh2 is a ginsenoside extracted from ginseng that has drawn attention in a few laboratories in Asian countries because of its potential tumor-inhibitory effect. In the present study, we tested Rh2 on many tumor-cell lines for its effects on cell proliferation, induction of apoptosis, and potential interaction with conventional chemotherapy agents. Our results showed that Rh2 inhibited cell growth by G1 arrest at low concentrations and induced apoptosis at high concentrations in a variety of tumor-cell lines, possibly through activation of caspases.