• BMB Reports
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• v.57 no.7
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• pp.336-341
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• 2024

Lung cancer is one of the most significant malignancies, with both high morbidity and mortality. CDK10 is closely related to cancer progression and metastasis. However, its role in lung cancer radioresistance demands further clarification. In this study, we demonstrated that CDK10 was downregulated in lung cancer tissues, and CDK10 expression level was associated with the clinical prognosis in lung cancer patients. We also found that silencing CDK10 promoted lung cancer cell proliferation, migration, and radioresistance. We further verified that silencing CDK10 facilitated the activation of JNK/c-Jun signaling, and c-Jun depletion could reverse the effects of CDK10 knockdown in lung cancer cells. Our findings revealed that CDK10 plays an important role in cell growth and radioresistance by inhibiting JNK/c-Jun signaling pathway in lung cancer. Therefore, CDK10 might be a promising therapeutic target in lung cancer.

• Environmental Mutagens and Carcinogens
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• v.25 no.2
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• pp.51-59
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• 2005

Overexpression of HSP25 delayed cell growth, increased the level of $p21^{waf}$, reduced the levels of cyclin D1, cylcin A and cdc2, and induced radioresistance in L929 cells. We demonstrated that extracellular regulated kinase (ERK) and MAP kinase/ERK kinase (MEK) expressions as well as their activation (phospho-forms) were inhibited by hsp25 overexpression. To confirm the relationship between ERK1/2 and hsp25-mediated radioresistance, ERK1 or ERK2 cDNA was transiently transfected into the hsp25 overexpressed cells and their radioresistance was examined. HSP25-mediated radioresistance was abolished by overexpression of ERK2, but not by overexpression of ERK1. Alteration of cell cycle distribution and cell cycle related protein expressions (cyclin D, cyclin A and cdc2) by hsp25 overexpression were also recovered by ERK2 cDNA transfection. Increase in Bc1-2 protein by hsp25 gene transfection was also reduced by subsequent ERK2 cDNA-transfection. In addition, HSP25 overexpression reduced reactive oxygen species (ROS) and increased expression of manganese superoxide dismutase (MnSOD) gene. Increased activation of NF-kB (IkB degradation) was also found in hsp25-overexpressed cells. Moreover, transfection of hsp25 antisense gene abrogated all the HSP25-mediated phenomena. To further elucidate the exact relationship between MnSOD induction and NF-kB activation, dominant negative $I-kB\alpha(I-kB\alpha-DN)$ construction was transfected to HSP25 overexpressed cells. $I-kB\alpha-DN$ inhibited HSP25 mediated MnSOD gene expression. In addition, HSP25 mediated radioresistance was blocked by $I-kB\alpha-DN$ transfection. Blockage of MnSOD with antisense oligonucleotides in HSP25 overexpressed cells, prevented apoptosis and returned the ERK1/2 activation to the control level. From the above results, we suggest for the first time that reduced oxidative damage by HSP25 was due to MnSOD-mediated down regulation of ERK1/2.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10115-10119
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• 2015

Purpose: The aim of this study was to investigate effects of adipose-derived mesenchymal stem cells (AMSCs) on radioresistance of breast cancer cells. Materials and Methods: MTT assays were used to detect any influence of AMSC supernatants on proliferation of breast cancer cells; cell migration assays were used to determine the effect of breast cancer cells on the recruitment of AMSCs; the cell survival fraction post-irradiation was assessed by clonogenic survival assay; ${\gamma}$-H2AX foci number post-irradiation was determined via fluorescence microscopy; and expression of IGF-1R was detected by Western blotting. Results: AMSC supernatants promoted proliferation and radioresistance of breast cancer cells. Breast cancer cells could recruit AMSCs, especially after irradiation. IGF-1 derived from AMSCs might be responsible for the radioresistance of breast cancer cells. Conclusions: Our results suggest that AMSCs in the tumor microenvironment may affect the outcome of radiotherapy for breast cancer in vitro.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5725-5730
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• 2013

Cancer patients often suffer from local tumor recurrence after radiation therapy. Cell cycling, an intricate sequence of events which guarantees high genomic fidelity, has been suggested to affect DNA damage responses and eventual radioresistant characteristics of cancer cells. Here, we established a radioresistant lung cancer cell line, A549R, by exposing the parental A549 cells to repeated ${\gamma}$-ray irradiation with a total dose of 60 Gy. The radiosensitivity of A549 and A549R was confirmed using colony formation assays. We then focused on examination of the cell cycle distribution between A549 and A549R and found that the proportion of cells in the radioresistant S phase increased, whereas that in the radiosensitive G1 phase decreased. When A549 and A549R cells were exposed to 4 Gy irradiation the total differences in cell cycle redistribution suggested that G2-M cell cycle arrest plays a predominant role in mediating radioresistance. In order to further explore the possible mechanisms behind the cell cycle related radioresistance, we examined the expression of Cdc25 proteins which orchestrate cell cycle transitions. The results showed that expression of Cdc25c increased accompanied by the decrease of Cdc25a and we proposed that the quantity of Cdc25c, rather than activated Cdc25c or Cdc25a, determines the radioresistance of cells.

• Genomics & Informatics
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• v.11 no.4
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• pp.245-253
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• 2013

A radioresistant cell line was established by fractionated ionizing radiation (IR) and assessed by a clonogenic assay, flow cytometry, and Western blot analysis, as well as zymography and a wound healing assay. Microarray was performed to profile global expression and to search for differentially expressed genes (DEGs) in response to IR. H460R cells demonstrated increased cell scattering and acidic vesicular organelles compared with parental cells. Concomitantly, H460R cells showed characteristics of increased migration and matrix metalloproteinase activity. In addition, H460R cells were resistant to IR, exhibiting reduced expression levels of ionizing responsive proteins (p-p53 and ${\gamma}$-H2AX); apoptosis-related molecules, such as cleaved poly(ADP ribose) polymerase; and endoplasmic reticulum stress-related molecules, such as glucose-regulated protein (GRP78) and C/EBP-homologous protein compared with parental cells, whereas the expression of anti-apoptotic X-linked inhibitor of apoptosis protein was increased. Among DEGs, syntrophin beta 2 (SNTB2) significantly increased in H460R cells in response to IR. Knockdown of SNTB2 by siRNA was more sensitive than the control after IR exposure in H460, H460R, and H1299 cells. Our study suggests that H460R cells have differential properties, including cell morphology, potential for metastasis, and resistance to IR, compared with parental cells. In addition, SNTB2 may play an important role in radioresistance. H460R cells could be helpful in in vitro systems for elucidating the molecular mechanisms of and discovering drugs to overcome radioresistance in lung cancer therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1289-1295
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• 2012

The use of herbal products as radiosensitizers is a promising approach to increase the efficacy of radiotherapy. However, adverse effects related to the use of herbal medicine on radiotherapy are not well characterized. The present study concerns the impact of Derris scandens Benth extract on the radiosensitivity of Hep-2 laryngeal cancer cells. Pretreatment with D. scandens extract prior to gamma irradiation significantly increased clonogenic survival and decreased the proportion of radiation-induced abnormal nuclei of Hep-2 cells. Furthermore, the extract was found to enhance radiation-induced G2/M phase arrest, induce Akt activation, and increase motility of Hep-2 cells. The study thus indicated that D. scandens extract potentiates radioresistance of Hep-2 cells, further demonstrating the importance of cellular background for the adverse effect of D. scandens extract on radiation response in a laryngeal cancer cell line.

• Korean Journal of Microbiology
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• v.18 no.1
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• pp.1-6
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• 1980

Five species of food decay fungl, Aspergillus flavus, Asp. uiger, Penicillum sp., Botrytis cinerea, and Rhizopus stolonifer, were examined for their radio sensitivity in several suspension media. Asp. flavus, Asp. niger and Penicillum sp. have almost the same sensitivity toward gamma rays. with D value in the range of 30 to 35 K rad, whereas Botrytis cinerea has a D value of approximately 55K rad and Rhizopus stolonifer, the most re4sistant fungus studied, has a crease in their radioresistnace when compared with spores irradiated in water. Asp. flavus and penicillium sp. spores irradiated in citrate buffer at pH3-7 showed almost no change in their radisensitiity with pH, but Botryis cinerea spores showed a distinct decrease in their radioresistnace at pH 6 and 7. Penicillum sp. spores irradiated in sucrose solutions showed no sinificant change in their radioresistance. Botrytis cinerea spores displayed a higher radioresistance when they were irradiated in sucrose solution than in water.

• Journal of Radiation Protection and Research
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• v.21 no.2
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• pp.99-105
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• 1996

After high-dose irradiation(8 Gy). the viability of lymphocyte with a prior low-dose irradiation was 3.7-fold higher than that without a prior low-dose irradiation The viability could be increased by the reduction of oxygen radicals or the removal of damaged molecules-DNA, protein. lipid membrane. or the removal of damaged cells. In this paper. we studied the radioresistance mechanism in lymphocytes and lymphoma cells by examining the activities of radical scavengers(catalase. peroxidase, superoxide dismutase, and glucose-6-phosphate dehydrogenase), and a radical protector(glutathione). Different enzymes were induced in lymphocyte and lymphoma with low-dose irradiation. The activity of peroxidase increased most(133.3%) in lymphoma while the enzymes increased most in lymphocyte were superoxide dismutase (138.5%), glucose-6-phosphate dehydrogenase (122.4%) and glutathione(120.8%). The activities of these enzymes were highest when the interval was 7 hours between low-dose and high-dose irradiation.

• FLOWER RESEARCH JOURNAL
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• v.19 no.2
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• pp.119-125
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• 2011

Acorus calamus is an indigenous hydrophyte used as phytoremediation and water purification as well as medicinal herb. Irradiation of gamma ray was performed to investigate the effect on radioresistance of A. calamus on in vitro. Various doses (20-500 Gy) of gamma rays were irradiated to in vitro plantlets. The effect of irradiation was studied on survival rate, shoot formation and growth rate. The survival and multiplication rate was remarkably decreased with the increase of radiation dose. The growth of plantlets was significantly increased in comparison to the control at low doses. The hermetic effect of radiation was appeared in A. calamus. It was significantly decreased or interrupted above 250 Gy. The mean 50% lethal dose ($LD_{50}$) was extremely high as 240 Gy. We conclude that A. calamus had remarkably high radioresistance compared with other plant species.

• Parasites, Hosts and Diseases
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• v.49 no.4
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• pp.423-426
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• 2011

In the genus Cryptosporidium, there are more than 14 species with different sizes and habitats, as well as different hosts. Among these, C. parvum and C. hominis are known to be human pathogens. As C. parvum can survive exposure to harsh environmental conditions, including various disinfectants or high doses of radiation, it is considered to be an important environmental pathogen that may be a threat to human health. However, the resistance of other Cryptosporidium species to various environmental conditions is unknown. In this study, resistance against ${\gamma}$-irradiation was compared between C. parvum and C. muris using in vivo infection in mice. The capability of C. muris to infect mice could be eliminated with 1,000 Gy of ${\gamma}$-irradiation, while C. parvum remained infective in mice after up to 1,000 Gy of ${\gamma}$-irradiation, although the peak number of oocysts per gram of feces decreased to 16% that of non-irradiated oocysts. The difference in radioresistance between these 2 Cryptosporidium species should be investigated by further studies.