PURPOSE To establish a novel, targeted lentivirus-mediated LEP503-HSV-tk/GCV suicide gene therapy system combined with all trans-retinoic acid (ATRA) for the inhibition of human lens epithelial cell (HLEC) proliferation and treatment of posterior capsular opacification (PCO) after cataract surgery; to estimate the enhancement of the bystander effect by ATRA; and to explore the role of Connexin4...

The efficacy of cancer gene therapy depends critically on "bystander effects" by which genetic modification of tumor cells results in killing of unmodified cells in the local microenvironment. In gene-dependent enzyme-prodrug therapy, expression of a prodrug-activating suicide gene is used to generate a cytotoxic metabolite that diffuses to nontransduced cells. The objective of this study was t...

Radiation-induced bystander effects have been observed in vitro and in cell and tissue culture models, however, there are few reported studies showing these effects in vivo. To our knowledge, this is the first reported study on bystander effects induced by microbeam irradiation in an intact living mammal. The mouse ear was used to investigate radiation-induced bystander effects in keratinocytes...

BACKGROUND The response of eukaryotic cells to double-strand breaks in genomic DNA includes the sequestration of many factors into nuclear foci. Recently it has been reported that a member of the histone H2A family, H2AX, becomes extensively phosphorylated within 1-3 minutes of DNA damage and forms foci at break sites. RESULTS In this work, we examine the role of H2AX phosphorylation in focus...

Biological effectiveness varies with the linear energy transfer (LET) of ionizing radiation. During cancer therapy or long-term interplanetary manned explorations, humans are exposed to high-LET energetic heavy ions that inactivate cells more effectively than low-LET photons like X-rays and gamma-rays. Recent biological studies have illustrated that heavy ions overcome tumor radioresistance cau...

Background: Radio-adaptive response and bystander effects are known phenomena occurring in cells following exposure to ionizing radiation (IR). In this study we examined possible radio-adaptation of lymphocytes following bystander effects induced by CHO-K1 cells. Materials and Methods: Whole blood and CHO-K1 cells were cultured in RPMI-1640 complete medium. Cells were separately irradiated with...

BACKGROUND To test our hypothesis that eutopic secretory phase endometrium from women with endometriosis is similar to proliferative phase endometrium from fertile women without endometriosis, we explored the expression of regulators of cell fate across the menstrual cycle. METHODS Endometrial biopsies were taken from 73 women, comprising 38 women with surgically diagnosed active peritoneal e...

The success of criminal acts can sometimes depend critically on the oversight or negligence of uninvolved bystanders (e.g., someone leaving a first-floor window open). Four studies examined how the contribution of a negligent bystander affects blame for the perpetrator of a crime. Although participants stated that discounting blame for the perpetrator was normatively inappropriate in this conte...

Gene directed enzyme prodrug therapy (GDEPT) of cancer aims to improve the selectivity of chemotherapy by gene transfer, thus enabling target cells to convert nontoxic prodrugs to cytotoxic drugs. A zone of cell kill around gene-modified cells due to transfer of toxic metabolites, known as the bystander effect, leads to tumour regression. Here we discuss the implications of either striving for ...