Cisplatin-controlled p53 gene therapy for human non-small cell lung cancer xenografts in athymic nude mice via the CArG elements.

Cisplatin, a commonly used chemotherapeutic agent, causes tumor cell death by producing DNA damage and generating reactive oxygen intermediates, which have been reported to activate the early growth response-1 (Egr-1) promoter through specific cis-acting sequences, termed CArG elements. The aim of this study was to construct an adenoviral vector containing CArG elements cloned upstream of the cDNA for human wt-p53, and to observe the effect of this vector on human non-small cell lung cancer (NSCLC) xenografts in athymic nude mice when combined with cisplatin treatment. The adenoviral vector AdEgr-p53 was generated by inserting CArG elements upstream of human wt-p53 cDNA.

Detecting normal cell radiosensitivity via assay of DNA damage in lymphocytes for individualizing radiotherapy in head and neck cancer patients.

Purpose: The purpose of this study was to determine whether the distribution of radiosensitivities in normal tissues of head and neck cancer patients, measured using a DNA damage assay on lymphocytes, is likely to provide sufficient discrimination to enable reliable identification of patients with abnormal sensitivities.

Material And Methods: Radiosensitivity was assessed in 307 lymphocyte samples from unselected head and neck cancer patients and was quantified as the initial number of DNA double-strand breaks (dsb) induced per Gray and per DNA unit (200 Mbp).

Results: The existence of an inter-individual variation in the radiosensitivity parameter is described by the range (0.

Correlation between DNA repair capacity in lymphocytes and acute side effects to skin during radiotherapy in nasopharyngeal cancer patients.

Purpose: Repair of radiation-induced DNA damage plays a critical role for both the susceptibility of patients to side effects after radiotherapy and their subsequent cancer risk. The study objective was to evaluate whether DNA repair data determined in vitro are correlated with the occurrence of acute side effects during radiotherapy.

Experimental Design: Nasopharyngeal cancer patients receiving radiation therapy were recruited in a prospective epidemiologic study.

[HSV-TK gene therapy of lung adenocarcinoma xenografts using a hypoxia/radiation dual-sensitive promoter].

Background & Objective: Radio-genetic therapy is a novel strategy for cancer treatment; however, a limited success was shown due to lower sensitivity of tumor cells to radiation under hypoxia, which is a unique feature for solid tumors. In order to improve the efficacy of radiogenetic therapy for lung cancer, a hypoxia/radiation dual-sensitive promoter was constructed to enhance the expression of HSV-TK in transfected cells exposed to radiation under hypoxia.

Methods: The chimeric promoter HRE-Egr was generated by insertion of hypoxia response elements (HREs) upstream of the Egr-1 (early growth response gene-1) promoter.

[Oncostatin M gene therapy in mice bearing lung adenocarcinoma xenograft using a hypoxia/radiation dual-sensitive promoter].

Objective: To improve the efficacy of radiogenetic therapy for lung cancer, a hypoxia/radiation dual-sensitive promoter was constructed to enhance the expression of oncostatin M (OSM) in transfected cells exposed to radiation under hypoxia.

Methods: The chimeric promoter HRE-Egr was generated by insertion of hypoxia response elements (HREs) upstream of the Early growth response gene-1 (Egr-1) promoter. OSM expression vector was constructed by cloning HRE-Egr promoter upstream of OSM gene, which was transfected into A549 cells.