1. Abstract 2. Introduction 3. Molecular Biologic Targets in Pancreatic Cancer 3.1. p53 3.2. K-ras 3.3. DPC-4, p16, and Rb 3.4. Bcl-2 3.5. Others 4. Methods for Gene Transfer 4.1. Viruses 4.1.1. Retroviruses 4.1.2. Adenoviruses 4.1.3. Adeno-associated viruses 4.2. Liposomes 4.3. Naked DNA technology 5. Manipulation of Genetic Targets 5.1. Restoration of Tumor Suppressor Genes and Anti-Oncogene ...

Tumor cells become sensitive to the inert prodrug cyclophosphamide (CPA) after transfer of the gene encoding cytochrome P450 2B1. This enzyme activates CPA into 4-hydroxycyclophosphamide, which ultimately degrades into acrolein and phosphoramide mustard, the anticancer and DNA-alkylating metabolite. It is imperative that any prodrug-activating gene therapy strategy against cancer possess the ca...

Agents stabilizing G-quadruplexes have the potential to destroy the functional structure of telomere and could therefore act as antitumor agents. We previously reported that SYUIQ-5 could stabilize G-quadruplex, induce senescence, and inhibit c-myc gene promoter activity. In this study, we showed that SYUIQ-5 inhibited proliferation of CNE2 and HeLa cancer cells, triggered a rapid and potent te...

Clustering of apoptotic cells is a characteristic of many developing or renewing systems, suggesting that apoptotic cells kill bystanders. Bystander killing can be triggered experimentally by inducing apoptosis in single cells and may be based on the exchange of as yet unidentified chemical cell death signals between nearby cells without the need for cell-to-cell communication via gap junctions...

Current anticancer therapy may be one of the most important exogenous sources of exposure to genotoxic agents in US, Japan, and Europe, where approximately 40-55 percent of the population is diagnosed with cancer at a certain point in their life. This review focuses on recent efforts to integrate a novel biomarker, gamma-H2AX, into anticancer drug screening to classify the mode of action (MoA) ...

Phosphorylation of histone H2AX on serine 139 (gamma-H2AX, gammaH2AX) occurs at sites flanking DNA double-strand breaks (DSBs) and can provide a measure of the number of DSBs within a cell. Here we describe a rapid and simple flow-cytometry-based method, optimized to measure gamma-H2AX in non-fixed peripheral blood cells. No DSB induced signal was observed in H2AX-/- cells indicating that our F...

Background: Protection of hematopoietic system has become a primary goal in the development of novel medical countermeasures against ionization radiation and radiotherapy. This study was to explore the role of rapamycin in normal tissues against radiation. Materials and Methods: Mice were pretreated with rapamycin by i.p. every other day for five times before 5 Gy or 8.5 Gy γ-ray whole bo...

Direct cellular DNA damage may lead to genome destabilization in unexposed, bystander, cells sharing the same milieu with directly damaged cells by means of the bystander effect. One proposed mechanism involves double strand break (DSB) formation in S phase cells at sites of single strand lesions in the DNA of replication complexes, which has a more open structure compared with neighboring DNA....

Double-strand break (DSB) damage in yeast and mammalian cells induces the rapid ATM (ataxia telangiectasia mutated)/ATR (ataxia telangiectasia and Rad3 related)-dependent phosphorylation of histone H2AX (gamma-H2AX). In budding yeast, a single endonuclease-induced DSB triggers gamma-H2AX modification of 50 kb on either side of the DSB. The extent of gamma-H2AX spreading does not depend on the c...