This study aimed to investigate the cell-killing effect of HSV-tk/GCV suicide gene system driven by β-globin matrix attachment region (MAR) on ECA109 cells and its bystander effect. The integration and expression of lentivirus vectors HSV-tk and MAR-HSV-tk in ECA109 were identified using RT-PCR and Western blot; the cell survival rate and cell-killing bystander effect were detected in different...

Brostallicin is a DNA minor groove binder in phase II clinical trials. Here, we show that brostallicin induces gamma-H2AX nuclear foci that colocalize with 53BP1 and are dependent on glutathione, as shown by inhibition of those gamma-H2AX foci by l-buthionine sulfoximine. To differentiate brostallicin from the clinically approved minor groove binder trabectedin (ecteinascidin 743), we tested wh...

background: h2ax is a histone variant that is systematically found and ubiquitously distributed throughout the genome. dna double-strand breaks (dsbs) induce phosphorylation of h2ax at serine 139 (γh2ax), an immunocytochemical assay with antibodies recognizing γh2ax has become the gold standard for the detection of dsbs. the importance of this assay to investigate different individual responses...

BACKGROUND To investigate the effects of S-phase kinase protein 2 (SKP2) expression on the radiation induced bystander effect (RIBE) in esophageal cancer (EC) cells. MATERIALS AND METHODS Western blot was used to detect the levels of SKP2, Rad51, and Ku70 in EC cells. Positive transfection, RNAi, micronucleus (MN), and γ-H2AX focus formation assay were used to investigate the effects of SKP2 ...

Matrix metalloproteinase (MMP)-1 promotes ultraviolet (UV)-triggered long-term detrimental effects such as cancer formation and premature skin aging. Although histone modifications may play a crucial role in the transcriptional regulation of MMP-1, the relationship between UV-induced histone modification and MMP-1 expression is not completely understood. Here, we identify regulators of histone ...

The histone H2A variant H2AX is rapidly phosphorylated in response to DNA double-stranded breaks to produce gamma-H2AX. gamma-H2AX stabilizes cell-cycle checkpoint proteins and DNA repair factors at the break site. We previously found that the protein phosphatase PP2A is required to resolve gamma-H2AX foci and complete DNA repair after exogenous DNA damage. Here we describe a three-protein PP4 ...

Background: Studies have reported the beneficial effects of exercise, ozone therapy, and stem cell therapy for the treatment of knee osteoarthritis.  Objectives: To reduce the duration of the treatment, we decided to investigate the synergistic effects of Endurance Training (ET), ozone therapy, and mesenchymal stem cell (MSCs) therapy separately or in combination on the cannabinoid receptors 1...

Background: Recently, the Flattening Filter Free (FFF) beams, which allow a dose rate increase of up to four times compared to the normal dose rate, have been incorporated into radiation therapy machines. The aim of this study is to evaluate antitumor activity in hypoxic cells irradiated with different dose rates using FFF beams and to identify the casual mechanism for cellular damage during ir...

A major focus of gene therapy for cancer has been the effort to introduce into cancer cells a number of foreign genes that encode enzymes that will selectively convert nontoxic prodrugs into toxic compounds, producing high local concentrations that result in tumor cell killing—so-called “suicide” gene therapy. A number of enzyme/prodrug systems have been described [reviewed in (1)], including h...