-
[show abstract]
[hide abstract]
ABSTRACT: A major concern in cancer therapy is resistance of tumors such as human non-small cell lung cancer and esophageal cancer to radiotherapy. Intrinsic radioresistance of these cancer cells limits therapeutic efficiency. Here, we determined in two cancer cell lines the potential radiosensitizing activity of Tat-SmacN7, a small molecule compound, which mimics the activity of Smac, a mitochondrial protein released during apoptosis. We found that Tat-SmacN7 can enter the cells and promote RNA expression and the activity of caspase-3, -8 and -9 and sensitized the cancer cells to radiation with a sensitization enhancement ratio (SER) of 1.5-1.6. Tat-SmacN7 radiosensitization was mediated by both extrinsic and intrinsic apoptosis pathways through activation of caspases. Consistently, blockage of caspase activation, through treatment with a caspase inhibitor, z-VAD-fmk, inhibited apoptosis and abrogated Tat-SmacN7 radiosensitization. Our study demonstrates that Tat-SmacN7 also has radiosensitization effects in vivo, so it could be further developed as a novel class of radiosensitizers for the treatment of radioresistant human non-small cell lung cancer and esophageal cancer.
International Journal of Oncology 01/2013; · 2.40 Impact Factor
-
Physica Medica 05/2012; · 1.07 Impact Factor
-
Environmental Science and Pollution Research 04/2012; 19(6):2460-2. · 2.65 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This paper introduces a software program that was developed with the aims to improve the efficiency and veracity of calibration curve fitting and data processing in radiation biological dosimetry and other biological experiments, and which is termed BioDoser. BioDoser uses least squares and loop testing of monotonicity method and algorithm of non-uniformed confidence interval. In addition, this program enables integration of multiple different biomarkers typically used in biological dosimetry. These include partial body exposure, minimum number of cells to be analyzed, G function correction modules that are helpful in dose estimation when using chromosome aberration frequencies, micronucleus rate, comet assay and other biological methods. The software is freely available at http://bit.ly/kKBSNR.
Computer methods and programs in biomedicine 04/2012; 108(1):402-6. · 1.14 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Osteosarcoma is the common primary bone malignancy in children and young adults in Eastern countries. Resistance to ionizing radiation (IR) or drugs is an underlying mechanism contributing to the failure of therapy in these patients. Rad51 is the key protein of DNA homologous recombination repair. Although high expression of Rad51 is associated with enhanced resistance to DNA damage induced by chemicals and/or ionizing radiation, the relevance of Rad51 expression in osteosarcoma and its relationship with IR sensitivity and chemo-resistance is not well understood. In this study, we elucidated the possibility of using Rad51 in the treatment of human osteosarcoma in vitro. Changes in chemo- and radiation sensitivity in cultured osteosarcoma cells occurred after suppression of Rad51 expression, using a plasmid vector-mediated short hairpin RNA (shRNA) expression system. The suppression of Rad51 correlated with cell cycle arrest in the G2 phase and inhibited tumor cell proliferation. Our results suggest that Rad51 expression levels might play an important role in radiation- and chemo-sensitivity of human osteosarcoma.
Medical Oncology 12/2011; 28(4):1481-7. · 2.14 Impact Factor
-
Radiology 10/2011; 261(1):329-30. · 5.73 Impact Factor
-
Qiang Liu, Jia Cao,
Ying Liu,
Yu Min Lü,
Bin Qin,
Bo Jiang,
Li Ping Jiang,
Bao Hua Fu,
Feng Ling Zhao,
En Hai Jiang,
Xu Su,
Fei Yue Fan
[show abstract]
[hide abstract]
ABSTRACT: The goal of this study was to assess the persistence of chromosomal aberrations and micronuclei of three victims 2 y after accidental radiation exposure to Co gamma rays. Traditional chromosome aberration analysis was performed by scoring the dicentric chromosomes (dic) and rings (r) in peripheral blood lymphocytes. Micronuclei were detected using the cytokinesis block micronucleus assay. G-banding and semi-automatic karyotype analysis was used to record translocations (t), inversions (inv) and deletions (del). The frequency of unstable chromosomal aberrations (dicentrics and rings) remained at high levels 6 mo after the accident. Two years after exposure, the frequency was reduced to 4-11% in the three victims. However, stable chromosome aberrations, which were detected by G-banding and included t, inv, and del, remained at a high level and have an obvious dose-dependent relationship even 2 y post-exposure. The frequency of micronuclei decreased faster than that of chromosome aberrations, reaching almost a normal level two years after the accident, especially for the child victim. Unstable chromosome aberrations reduced gradually, but the stable aberration remained at a high level along with the time-lapse. The micronucleus assay was less valuable for assessing long-term effects after high dose irradiation.
Health physics 06/2010; 98(6):885-8. · 0.92 Impact Factor
-
Environmental Science and Pollution Research 12/2009; 17(2):247-9. · 2.65 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: It has been known that the pollutants of electronic wastes (E-wastes) can lead to severe pollution to the environment. It has been reported that about 50% to 80% of E-wastes from developed countries are exported to Asia and Africa. It has become a major global environmental problem to deal with 'E-wastes'. E-waste recycling has remained primitive in Jinghai, China. This not only produces enormous environmental pollution but also can bring about toxic or genotoxic effects on the human body, threatening the health of both current residents and future generations living in the local environment. The concentration of lead in the blood of children in the E-waste polluted area in China is higher than that of the control area. But little is known about the cytogenetic effect to human beings caused by the pollution of E-wastes. In the present study, experiments have been performed to investigate the genetics of permanent residents of three villages with numerous E-waste disposal sites and to analyze the harmful effects of exposure to E-wastes.
In total, 171 villagers (exposed group) were randomly selected from permanent residents of three villages located in Jinghai County of Tianjin, China, where there has been massive disposal of E-wastes. Thirty villagers were selected from the neighboring towns without E-waste disposal sites to serve as controls. Chromosomal aberrations and cytokinesis blocking micronucleus were performed to detect the cytogenetic effect, dic + r (dicentric and ring chromosome), monomer, fragments (acentric fragments, minute chromosomes, and acentric rings), translocation, satellite, quadriradial, total aberrations, and micronuclear rate were scored for each subject. DNA damage was detected using comet assay; the DNA percentage in the comet tail (TDNA%), tail moment (TM), and Olive tail moment (OTM) were recorded to describe DNA damage to lymphocytes.
The total chromosome aberration rates (5.50%) and micronuclear rates (16.99%) of the exposure group were significantly higher than in the control group (P = 0.000). The percentage of DNA in the comet tail, tail moment, and Olive tail moment detected by comet assay showed that there was a significant difference in DNA damage in the exposure group (P = 0.000). The chromosome aberration, micronucleus rate, and DNA damage observed in women were significantly higher than those in men. Chromosome aberration and micronuclear rates of both smokers and non-smokers in the exposure group are obviously higher than that in the control group (P = 0.000).
The use of outdated (and unsafe) ways to deal with E-wastes can lead to exposure to a variety of substances harmful to human health. The components of pollution may enter the human body through the air, drinking water, and food chain to damage human genetic material, resulting in genomic instability. The rates of chromosomal aberration, micronucleus formation, and the degree of DNA damage in women in the group exposed to electronic waste were significantly higher than in men. The reason for this may be concerned with the traditional lifestyle of the local residents or the difference of sensitivity to the exposure to E-wastes or any others. Further investigations are needed to provide evidence to demonstrate this.
Here, we report the obviously cytogenetic toxicity to the exposure population by the E-waste pollution for the first time. E-waste pollution may be a potential agent of genetic mutation, and may induce cytogenetic damage within the general population exposed to the pollution. These findings need to be considered, and steps should be taken to protect the current population and future generations from the effects of pollution with E-wastes.
The above results remind us that the impact of E-waste recycling on environmental quality of Jinghai should be evaluated soon. Moreover, it is urgent for the government to prohibit E-waste import and its processing by outdated ways. The future studies such as pollutant details of drinking water, air, and soil in the area as well as epidemiological investigations on the harmful effect to children must be performed eagerly. All the data available do provide a compelling case for immediate action in both countries to address workplace health and safety and waste management.
Environmental Science and Pollution Research 01/2009; 16(3):329-38. · 2.65 Impact Factor
