MLN4924 is an investigational small-molecule inhibitor of the Nedd8-activating enzyme currently in phase I clinical trials. MLN4924 induces DNA damage via rereplication in most cell lines. This distinct mechanism of DNA damage may affect its ability to combine with standard-of-care agents and may affect the clinical development of MLN4924. As such, we studied its interaction with other DNA-dama...

PURPOSE To compare various techniques of pterygium surgery including bare sclera, intraoperative mitomycin C application, conjunctival flap reconstruction, and conjunctival autografting technique. METHODS This study is designed to compare 4 currently used techniques in order to determine the complication and recurrence rates after pterygium exision. Included in the study were 77 eyes from 60 ...

We have previously reported the isolation of CHO cell lines resistant to mitomycin C under aerobic conditions of drug exposure. Here it is reported that these cell lines have the same response to mitomycin C under hypoxic conditions as do controls. The cells are shown to have lower levels of DT-diaphorase activity than controls, but similar levels of activity of NADPH:cytochrome c reductase, an...

BACKGROUND Mitomycin C is used in the immediate post-operative period to prevent tumor re-implantation, but it has adverse effects on the bladder. This study devised an animal model to investigate the effects of intravesical mitomycin C on wound healing. METHODS AND MATERIALS A cystotomy was made in the dome of the bladder of female rats. The mucosa of the posterior wall was scratch with clos...

Hypoxic cells of solid tumors are relatively resistant to therapeutic assault. Studies have demonstrated that oxygen-deficient tumor cells exist in an environment conducive to reductive reactions making hypoxic cells particularly sensitive to bioreductive alkylating agents. Mitomycin C, the prototype bioreductive alkylating agent available for clinical use, is capable of preferentially killing ...

BACKGROUND The purpose of the present study is to quantify the in vitro antiproliferative and cytotoxic effects of mitomycin-C on human keratocytes for their potential to modulate corneal stromal wound healing. METHODS Cultured human keratocytes were exposed to various concentrations of mitomycin-C for periods of 5 minutes and 1 hour. Keratocyte proliferation and viability were assessed by ph...

The use of histone deacetylase inhibitors has been proposed as a promising approach to increase the cell killing effect of DNA damage-inducing drugs in chemotherapy. However, the molecular mechanism of their action remains understudied. In the present article, we have assessed the effect of the histone deacetylase inhibitor sodium butyrate on the DNA damage response induced by the crosslinking ...

background: photorefractive keratectomy is a popular mean to correct refractive errors of the eye and haze formation is one of the most important complications of the surgery. although standard dose of intraoperative mitomycin c has shown to be effective in reduction of this complication, potential side effects of mitomycin c promote us to show if the lower concentration of mitomycin c has t he...

OBJECTIVES The aim of the present study was to evaluate the efficacy and short-term safety of topical mitomycin-C, an antifibrotic agent, in preventing the recurrence of anastomotic strictures after surgical repair of esophageal atresia (EA). METHODS We retrospectively reviewed the medical records of patients with recurrent anastomotic strictures after EA surgery who underwent at least 3 esop...

Both the ERCC1-XPF complex and the proteins involved in homoIogous recombination (HR) have critical roles in inter-strand cross-link (ICL) repair. Here, we report that mitomycin C-induced lesions inhibit replication fork elongation. Furthermore, mitomycin C-induced DNA double-strand breaks (DSBs) are the result of the collapse of ICL-stalled replication forks. These are not formed through repli...