• Nuclear Engineering and Technology
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• v.54 no.4
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• pp.1439-1448
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• 2022

Background: We investigated the feasibility of in vitro radiosensitivity prediction with gene expression using deep learning. Methods: A microarray gene expression of the National Cancer Institute-60 (NCI-60) panel was acquired from the Gene Expression Omnibus. The clonogenic surviving fractions at an absorbed dose of 2 Gy (SF2) from previous publications were used to measure in vitro radiosensitivity. The radiosensitivity prediction model was based on the convolutional neural network. The 6-fold cross-validation (CV) was applied to train and validate the model. Then, the leave-one-out cross-validation (LOOCV) was applied by using the large-errored samples as a validation set, to determine whether the error was from the high bias of the folded CV. The criteria for correct prediction were defined as an absolute error<0.01 or a relative error<10%. Results: Of the 174 triplicated samples of NCI-60, 171 samples were correctly predicted with the folded CV. Through an additional LOOCV, one more sample was correctly predicted, representing a prediction accuracy of 98.85% (172 out of 174 samples). The average relative error and absolute errors of 172 correctly predicted samples were 1.351±1.875% and 0.00596±0.00638, respectively. Conclusion: We demonstrated the feasibility of a deep learning-based in vitro radiosensitivity prediction using gene expression.

• Asian-Australasian Journal of Animal Sciences
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• v.2 no.3
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• pp.509-510
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• 1989

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.5975-5979
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• 2012

Background: To investigate the influence of telomerase activity, apoptosis, radiosensitivity of cervical cancer after siRNA-mediated knockdown of telomerase RNA and evaluate in vivo growth with gene interference. Methods: We studied siRNA-targeting-telomerase RNA transfection into the Hela cell line. Expression of hTERC mRNA was detected by RT-PCR and telomerase activity was measured by the TRAP assay. Growth inhibition was determined by MTT assay and radiosensitivity of the cervical cancer cells was examined by colony formation assay. In addtion, effects of hTERC inhibition in vivo were studied by injection of siRNA-transfected Hela cells into nude mice. Results: The hTERC siRNA effectively downregulated the expression of hTERC mRNA and also reduced the telomerase activity to 30% of the untreated control vlaue. The viability of hTERC siRNA transfected Hela cells was reduced by 44.7% after transfection. After radiation treatment, the radiosensitivity of Hela cells with hTERC knockdown was increased. In vivo, the tumors developing from the hTERC siRNA-transfected cells were of reduced size, indicating that the hTERT siRNA also depressed the tumorigenic potential of the Hela cells. Conclusions: Our results supported the concept of siRNA-mediated inhibition of telomerase mRNA which could inhibit the expression of hTERC and telomerase activity. Furthermore, radiosensitivity was upregulated after knockdown the hTERC in vivo and in vitro.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.193-203
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• 1993

In understanding radiosensitivity a new concept of inherent radiosensitivity based on individuality and heterogeneity within a population has recently been explored. There has been some discussion of possible mechanism underlying differences in radiosensitivity between cells. Ataxia telangiectasia (AT), a rare autosomal recessive genetic disorder, is characterized by hypersensitivity to ionizing radiation and other DNA damaging agents at the cellular level. There have been a lot of efforts to describe the cause of this hypersensitivity to radiation. At the cellular level, chromosome repair kinetics study would be an appropriate approach. The purpose of this study was to better understand radiosensitivity En an approach to investigate kinetics of induction and repair of $G_2$ chromatic bleaks using normal, AT heterozygous (ATH), and AT homozygous lymphoblastoid cell lines. In an attempt to estimate initial damage, $9-{\beta}-D-arabinosyl-2-fluoroadenine,$ an inhibitor of DNA synthesis and repair, was used in this study. It was found from this study that radiation induces higher chromatid breaks in AT than in normal and ATH cells. There was no significant differences of initial chromatid breaks between normal and ATH cells. Repair kinetics was the same for all. So the higher level of breaks in AT $G_2$ cells is thought to be a reflection of the increased initial damage. The amount of initial damage correlated well with survival fraction at 2 Gy of cell survival curve following radiation. Therefore, the difference of radiosensitivity in terms of $G_2$ chromosomal sensitivity is thought to result from the difference of initial damage.

• Nuclear Engineering and Technology
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• v.54 no.8
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• pp.3027-3033
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• 2022

Background: In this study, various types of deep-learning models for predicting in vitro radiosensitivity from gene-expression profiling were compared. Methods: The clonogenic surviving fractions at 2 Gy from previous publications and microarray gene-expression data from the National Cancer Institute-60 cell lines were used to measure the radiosensitivity. Seven different prediction models including three distinct multi-layered perceptrons (MLP), four different convolutional neural networks (CNN) were compared. Folded cross-validation was applied to train and evaluate model performance. The criteria for correct prediction were absolute error < 0.02 or relative error < 10%. The models were compared in terms of prediction accuracy, training time per epoch, training fluctuations, and required calculation resources. Results: The strength of MLP-based models was their fast initial convergence and short training time per epoch. They represented significantly different prediction accuracy depending on the model configuration. The CNN-based models showed relatively high prediction accuracy, low training fluctuations, and a relatively small increase in the memory requirement as the model deepens. Conclusion: Our findings suggest that a CNN-based model with moderate depth would be appropriate when the prediction accuracy is important, and a shallow MLP-based model can be recommended when either the training resources or time are limited.

• Korean journal of applied entomology
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• v.4
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• pp.67-74
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• 1965

The work on the 'Studies of radiosensitivity' in Korea has been initiated since 1959 by the author at various institutions in home and foreign countries, and more than 20000 of plant materials in 73 varieties and 41 kinds are treated under varied conditions for the studies of radiosensitivity in plants. However, a study of the susceptibility to radiation in insect pests as well as their biological effects has not been previously reported in this country. During the year of 1964 and 1965, near 50000 of insects at the stages of adult, egg, larva and pupa in 14 different kinds are irradiated under acute X and gamma rays to investigate the behavior of growth and lethality after irradiation, and thrir general tolerances to radiations are compared by the kind of insects, stage of growth, radiation sources and exposured dosages. Through the experiments, it is shown that the lethality in most of insects are high as several kilo roentgens above and no significant effects on pupation. emergence, and oviposition in the treated generation at the dose of 3 Kr. below, but in the following generation , the rice stem borer for instance, no oviposition or decreased laying is observed from the dosages at 3 Kr. to 1 Kr., and the hatching was possible from 1.5 Kr. below of irradiated larvae although laying and hatching are seemed in normal. In general, the lethal dose $50\%$ of tested infect materials at the larval stage can he classified some what 60-80 Kr. for Pine caterpillar, Fall webworm, Camphor silk moth and their relatives, at 40-60 Kr. for Gypsy moth, Monley prominent and some relatives and at 20-30 Kr. for House fly, Rice weevil, Pine sawfly etc. Plant parasitic nematodes such as Hirschmannia and Paratylenchus shown very high resistance to radiation and the LD-50 is observed from 100 Kr. or above. A concept to evaluate the radiosensitivity in insects by taxological family line as a practical measure is not answerable yet, but it ran he solved within the near future through the continuing experiments.

• Korean Journal of Environmental Agriculture
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• v.16 no.3
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• pp.216-219
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• 1997

Thirty day old rice seedlings, Ilpoom and Taeback variety, grown under deficient condition of several elements in nutrition solution of sand culture were exposed to 20Gy, 40Gy, 80Gy of gamma ray $(^{60}Co)$ to study the effect of their radiosensitivity. The results obtained are summarized as follows : Plant height and fresh weight of nutrient deficient rice plants were far less than those of control. The effect was different with nutrient element and rice variety, as show increasing effect of radiosensitivity in the Ilpoom variety was high in the Fe deficient whereas that of Taeback was high in the P deficient. Growth inhibition of rice plant irradiated with 20Gy was highly occurred in the Fe and Zn deficient plot in Ilpoom variety and P and Zn deficient plot in Taeback variety. In 80Gy irradiated group, radiosensitivity of rice plant was high in the P and Ca deficient plot of both Ilpoom and Taeback variety.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2975-2979
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• 2015

Background: Telomere length is closely associated with cellular radiosensitivity and WRAP53 is required for telomere addition by telomerase. In this research we assessed radiosensitivity of laryngeal squamous cell carcinoma Hep-2 cell lines after WRAP53 inhibition, and analyzed the molecular mechanisms. Materials and Methods: phWRAP53-siRNA and pNeg-siRNA were constructed and transfected into Hep-2 cells with lipofectamine. Expression of WRAP53 was analyzed by RT-PCR and Western-blottin, radiosensitivity of Hep-2 cells was assessed colony formation assay, and the relative length of telomeres was measured by QPCR. Results: The data revealed that the plasmid of phWRAP53-siRNA was constructed successfully, and the mRNA and protein levels of WRAP53 were both obviously reduced in the Hep-2 cell line transfected with phWRAP53-siRNA. After Hep-2 cells were irradiated with X-rays, the $D_0$ and $SF_2$ were 2.481 and 0.472, respectively, in the phWRAP53-siRNA group, much lower than in the control group ($D_0$ and $SF_2$ of 3.213 and 0.592) (P<0.01). The relative telomere length in the phWRAP53-siRNA group was $0.185{\pm}0.01$, much lower than in the untreated group ($0.523{\pm}0.06$) and the control group ($0.435{\pm}0.01$). Conclusions: Decreasing the expression of WRAP53 using RNA interference technique can enhance the radiosensitivity of Hep-2 cell lines by influencing the telomere length. WRAP53 is expected to be a new target to regulate the radiosensitization of tumor cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3301-3306
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• 2015

Nucleolin (C23) is an important anti-apoptotic protein that is ubiquitously expressed in exponentially growing eukaryotic cells. In order to understand the impact of C23 in radiation therapy, we attempted to investigate the relationship of C23 expression with the radiosensitivity of human non-small cell lung cancer (NSCLC) cells. We investigated the role of C23 in activating the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), which is a critical protein for DNA double-strand breaks (DSBs) repair. As a result, we found that the expression of C23 was negatively correlated with the radiosensitivity of NSCLC cell lines. In vitro clonogenic survival assays revealed that C23 knockdown increased the radiosensitivity of a human lung adenocarcinoma cell line, potentially through the promotion of radiation-induced apoptosis and adjusting the cell cycle to a more radiosensitive stage. Immunofluorescence data revealed an increasing quantity of ${gamma}$-H2AX foci and decreasing radiation-induced DNA damage repair following knockdown of C23. To further clarify the mechanism of C23 in DNA DSBs repair, we detected the expression of DNA-PKcs and C23 proteins in NSCLC cell lines. C23 might participate in DNA DSBs repair for the reason that the expression of DNA-PKcs decreased at 30, 60, 120 and 360 minutes after irradiation in C23 knockdown cells. Especially, the activity of DNA-PKcs phosphorylation sites at the S2056 and T2609 was significantly suppressed. Therefore we concluded that C23 knockdown can inhibit DNA-PKcs phosphorylation activity at the S2056 and T2609 sites, thus reducing the radiation damage repair and increasing the radiosensitivity of NSCLC cells. Taken together, the inhibition of C23 expression was shown to increase the radiosensitivity of NSCLC cells, as implied by the relevance to the notably decreased DNA-PKcs phosphorylation activity at the S2056 and T2609 clusters. Further research on targeted C23 treatment may promote effectiveness of radiotherapy and provide new targets for NSCLC patients.

• Radiation Oncology Journal
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• v.11 no.1
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• pp.17-27
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• 1993

To investigate the relationship between radiosensitivity and postirradiation recovery in human cancer cells, a study was performed using human cancer cell lines-A549, CaSki, SNU-C5 and PCI-13. For the study of radiosensitivity, single doses of 2, 4, 6, 8, 10, 12, and 14 Gy were given and for postirradiation recovery, two fractions of 4 Gy were separated with a time interval of 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, or 6 hours. Surviving fraction was estimated using colony forming ability. Surviving fractions at 2 Gy (SF2) were 0.496 (0.570-0.412) for A549, 0.496 (0.660-0.332) for CaSki, 0.386 (0.576-0.216) for SNU-C5, and 0.185 (0.247-0.123) for PCI-13. By statistical analysis the SF2 of PCI-13 was lower significantly than those of others (p<0.05). This difference was also observed at 4, 6 and 8 Gy dose levels. At 6 and 8 Gy the surviving fractions of SNU-C5 were also lower significantly than A549 and CaSki (p<0.05). By the analysis with linear quadratic model, the values of ${\alpha}$ for A549, CaSki, SNU-C5 and PCI-13 were 0.3016, 0.3212, 0.4327 and 0.8423, respectively, and those of ${\beta}$ were 0.02429, 0.02009, 0.03349 and 0.00059, respectively. So, the value of ${\alpha}$ showed increasing tendency with decreasing SF2. By the multitarget single hit model the values of Do for A549, CaSki, SUN-C5 and PCI-13 were 1.97, 1.97, 1.46 and 0.81, respectively, and those of n were 1.53, 1.50, 1.56 and 2.28, respectively. So, the value of Do decreased with decreasing SF2. Post-irradiation recovery reached plateau at around 2 hours. Recovery ratio at plateau phase ranged from 1.2 to 4.2; the value were 1.2 for PCI-13, 3.2 for CaSki, 3.3 for SNU-C5, and 4.2 for A549. Recovery rate well correlated with SF2, and increased with increasing Do and decreasing ${\alpha}$. According to above results, the intrinsic radiosensitivity was quite different among the tested cell lines; PCI-13 was the most sensitive and A549 and CaSki was similar. This difference of radiosensitivity is thought to be partly due to the difference in amount of postirradiation recovery. By linear quadratic model the difference of ${\alpha}$ values was very high, and by multitarget single hit model the difference of Do value was significantly high among four cell lines.