• Radiation Oncology Journal
• /
• v.28 no.4
• /
• pp.238-248
• /
• 2010

Purpose: To compare the dose distributions between three-dimensional (3D) and four-dimensional (4D) radiation treatment plans calculated by Ray-tracing or the Monte Carlo algorithm, and to highlight the difference of dose calculation between two algorithms for lung heterogeneity correction in lung cancers. Materials and Methods: Prospectively gated 4D CTs in seven patients were obtained with a Brilliance CT64-Channel scanner along with a respiratory bellows gating device. After 4D treatment planning with the Ray Tracing algorithm in Multiplan 3.5.1, a CyberKnife stereotactic radiotherapy planning system, 3D Ray Tracing, 3D and 4D Monte Carlo dose calculations were performed under the same beam conditions (same number, directions, monitor units of beams). The 3D plan was performed in a primary CT image setting corresponding to middle phase expiration (50%). Relative dose coverage, D95 of gross tumor volume and planning target volume, maximum doses of tumor, and the spinal cord were compared for each plan, taking into consideration the tumor location. Results: According to the Monte Carlo calculations, mean tumor volume coverage of the 4D plans was 4.4% higher than the 3D plans when tumors were located in the lower lobes of the lung, but were 4.6% lower when tumors were located in the upper lobes of the lung. Similarly, the D95 of 4D plans was 4.8% higher than 3D plans when tumors were located in the lower lobes of lung, but was 1.7% lower when tumors were located in the upper lobes of lung. This tendency was also observed at the maximum dose of the spinal cord. Lastly, a 30% reduction in the PTV volume coverage was observed for the Monte Carlo calculation compared with the Ray-tracing calculation. Conclusion: 3D and 4D robotic radiotherapy treatment plans for lung cancers were compared according to a dosimetric viewpoint for a tumor and the spinal cord. The difference of tumor dose distributions between 3D and 4D treatment plans was only significant when large tumor movement and deformation was suspected. Therefore, 4D treatment planning is only necessary for large tumor motion and deformation. However, a Monte Carlo calculation is always necessary, independent of tumor motion in the lung.

• Radiation Oncology Journal
• /
• v.26 no.4
• /
• pp.257-262
• /
• 2008

Purpose: Oral mucositis induced by radiotherapy to the head and neck area, is a common acute complication and is considered as the most severe symptom for cancer patients in the early stages of treatment. This study was proposed to establish the oral mucositis mouse model induced by a single dose of radiation for the facility of testing therapeutic candidates which can be used for the oral mucositis treatments. Materials and Methods: Fifty-five BALB/c mice were divided into four groups: control, 16 Gy, 18 Gy, and 20 Gy. Oral mucositis was induced by a single dose of radiation to the head and neck using 6 MV x-Ray from linear accelerator. After irradiation, body weight and physical abnormalities were checked daily. Tongue tissues from all groups were taken on days 1, 2, 3, 5, 7, 9, and 14, respectively and H&E staining was conducted to examine morphological changes. Results: Body weight dramatically decreased after day 5 in all irradiated mice. In the 16 Gy treatment group, body weight was recovered on day 14. The histology data showed that the thickness of the epithelial cell layer was decreased by the accumulated time after radiation treatment, up to day 9. Severe ulceration was revealed on day 9. Conclusion: A single dose of 16 Gy is sufficient dose to induce oral mucositis in Balb/C mice. Significant changes were observed in the Balb/C mice on days 7 and 9 after radiation. It is suggested that this mouse model might be a useful standard tool for studying oral mucositis induced by radiation.

• Radiation Oncology Journal
• /
• v.26 no.4
• /
• pp.289-294
• /
• 2008

Purpose: To improve the quality of the statistical analysis of papers published in the Journal of the Korean Society for Therapeutic Radiology and Oncology (JKOSTRO) by evaluating commonly encountered errors. Materials and Methods: Papers published in the JKOSTRO from January 2006 to December 2007 were reviewed for methodological and statistical validity using a modified version of Ahn's checklist. A statistician reviewed individual papers and evaluated the list items in the checklist for each paper. To avoid the potential assessment error by the statistician who lacks expertise in the field of radiation oncology; the editorial board of the JKOSTRO reviewed each checklist for individual articles. A frequency analysis of the list items was performed using SAS (version 9.0, SAS Institute, NC, USA) software. Results: A total of 73 papers including 5 case reports and 68 original articles were reviewed. Inferential statistics was used in 46 papers. The most commonly adopted statistical methodology was a survival analysis (58.7%). Only 19% of papers were free of statistical errors. Errors of omission were encountered in 34 (50.0%) papers. Errors of commission were encountered in 35 (51.5%) papers. Twenty-one papers (30.9%) had both errors of omission and commission. Conclusion: A variety of statistical errors were encountered in papers published in the JKOSTRO. The current study suggests that a more thorough review of the statistical analysis is needed for manuscripts submitted in the JKOSTRO.

• Korean Journal of Veterinary Research
• /
• v.41 no.2
• /
• pp.203-210
• /
• 2001

Here, we compared the effectiveness of 50 MeV($p{\to}RBe^+$) cyclotron fast neutrons versus $^{60}Co$ ${\gamma}$-rays by the apoptotic fragment frequency in both rat peripheral lymphocytes and crypt cells to check a radiobiological endpoint. The incidence of apoptotic cell death was increased in all irradiated groups, and radiation at all doses trigger rapid changes in both crypt cells and peripheral lymphocytes. These data suggest that apoptosis may play an important role in homeostasis of damaged radiosensitive target organ by removing damaged cells. The curve of dose-effect relationship for these data of apoptotic fragments frequencies was $y=0.3+(6.512{\pm}0.279)D(r^2=0.975)$ after neutrons, while $y=0.3+(4.435{\pm}0.473)D+(-1.300{\pm}0.551)D^2(r^2=0.988)$ after ${\gamma}$-rays. In addition, $y=3.5+(118.410{\pm}10.325)D+(-33.548{\pm}12.023)D^2(r^2=0.992)$ after ${\gamma}$-rays in rat lymphocytes. A significant dose-response relationship was found between the frequency of apoptotic cell and dose. These data show a trend towards increase of the numbers of apoptotic cells with increasing dose. Dose-response curves for high and low linear energy transfer (LET) radiation modalities in these studies were different. The relative biological effectiveness (RBE) value for crypt cells was 1.919. In addition, there were significant peaks on apoptosis induction at 4 and 6h after irradiation, and the morphological findings of the irradiated groups were typical apoptotic fragments in crypt cells that were hardly observed in the control group. Thus, apoptosis induction in both crypt cells and peripheral lymphocytes could be a useful endpoint of rat model for studying screening test and microdosimetic indicator to evaluate the biological effects of radiation-induced cell damage.

• Journal of Life Science
• /
• v.25 no.7
• /
• pp.801-809
• /
• 2015

Homotypic cell adhesion (homotypic aggregation) in activated monocytes plays a central role in physiological and pathological processes including inflammatory responses, differentiation and migration. The extract of the Prunus mume Sieb. et Zucc. fruit (Maesil) has potential benefits to human health; such as anti-viral, anti-microbial, and anti-cancer activities. Indeed, Maesil extract may modulate inflammatory responses via interference with homotypic aggregation in monocytes. In the present study, the molecular mechanisms underpinning the therapeutic efficacy of Maesil extract in inflammatory diseases were investigated. It was found that Maesil extract inhibited homotypic aggregation in lipopolysaccharide (LPS)-activated monocytes. This was mediated by reduction of nitric oxide (NO) production, partly via inhibition of inducible nitric oxide synthase (iNOS) expression in LPS-activated THP-1 cells. It was confirmed that NO inhibition is a key mechanism in Maesil induced blockade of monocyte aggregation through identification of reversal of this inhibitory effect by the NO-producing agent S-nitroso-N-acetyl penicillamine (SNAP). In addition, Maesil extract significantly attenuated LPS-induced IκB-α phosphorylation and NF-κB translocation into the nucleus. In conclusion, Maesil extract exerts anti-inflammatory effects via inhibition of homotypic aggregation of LPS-activated monocytes through mechanisms involving the suppression of NO production and NF-κB activity, suggesting Maesil extract as a potential therapeutic candidate for the prevention and treatment of chronic inflammatory diseases.

• Journal of Life Science
• /
• v.18 no.1
• /
• pp.16-22
• /
• 2008

In this study to evaluate the involvement of EGFR, HER-2/neu and ALCAM (CD166) oncogene products in canine mammary neoplastic lesions, sections of archived paraffin-embedded samples of 49 mammary tumors were analyzed immunohistochemically using antibodies against human EGFR and HER-2/neu and ALCAM. These 49 tumors were divided into 2 groups: 22 benign (19 adenoma, 3 benign mixed tumors) and 27 malignant tumors (2 simple adenocarcinomas, 5 complex adenocarcinomas, 3 solid carcinoma, 5 sclerosing carcinoma, 8 malignant mixed tumors and 4 malignant myoepithelioma). As a result of immunostaining, 31.8% (7/22) of the benign tumors and 29.6% (8/27) of the malignant tumors expressed the HER-2/neu oncogene product, EGFR expression was detected in 27.3% (6/22) of benign tumors and in 22.2% (6/27) of the malignant tumors. ALCAM expression was detected in 40.9% (9/22) of benign tumors and in 7.4% (2/27) of the malignant tumors. These results suggest that some of the biological and morphological characteristics of the tumor are associated with canine mammary gland tumors, as also reported for human breast cancer, the possibility of using anti-HER-2/neu antibodies in the treatment of canine mammary tumors.

• Journal of Life Science
• /
• v.19 no.11
• /
• pp.1637-1643
• /
• 2009

Shikonin, a component of Lithospermum erythrorhizon Sieb. et Zucc, exerts various characteristics such as anti-inflammatory, anti-cancer and anti-obesity functions. To elucidate the molecular mechanism of shikonin-induced inhibition of adipogenesis, we analyzed the mRNA expression level of various adipogenesis-related factors including C/EBPs (CCAAT/enhancerbinding proteins) and $PPAR{\gamma}$ (peroxisome proliferator-activated receptor $\gamma$). The data showed that mRNA expressions of C/$EBP{\beta}$ and C/$EPB{\delta}$ were only slightly changed by shikonin treatment, but mRNA expressions of $PPAR{\gamma}$ and C/$EPB{\alpha}$ were significantly down-regulated. Then, we tested whether upstream regulators of C/$EBP{\beta}$ and $PPAR{\gamma}$ were involved in anti-adipogenesis of shikonin. C/$EBP{\gamma}$ and CHOP (C/EBP homologous protein), which are upstream regulators of C/$EBP{\beta}$, were not affected by shikonin treatment. On the contrary, the mRNA level of KROX20 was markedly down-regulated by shikonin treatment. These results suggest that KROX20 might regulate downstream factors of adipogenesis through C/$EBP{\beta}$-independent pathway. The expression of KLF15 (Kruppel-like factor15), which is a member of KLF family and is a upstream regulator of $PPAR{\gamma}$, was dramatically decreased by shikonin treatment, but KLF2 was not changed. Shikonin had no impact on the expression of KLF5 in the early stage of adipogenesis, but shikonin increased expression of KLF5 in the late stage of adipogenesis. Even though mRNA expression of KLF5 was moderately changed by shikonin treatment, its effect may be small compared with the effect of KLF15, which was markedly inhibited. Taken together, these results suggest that shikonin inhibits adipogenesis through the down-regulation of $PPAR{\gamma}$ and C/$EPB{\alpha}$, which is mediated by the down-regulation of two pro-adipogenic factors, KROX20 and KLF15.

• Journal of Life Science
• /
• v.19 no.8
• /
• pp.1152-1158
• /
• 2009

For the toxicological pathologic study of amanita muscaria, we have investigated single and repeated dose toxicity in Sprague-Dawley (SD) rats. Single dose toxicity study was identified as catalepsy, incline and tail pinch methods (control 0 mg/kg, low 3.3 mg/kg, middle 16.5 mg/kg, high 33.0 mg/kg). Repeated dose toxicity study was carried out in blood tests, serum tests and histopathological methods. Neurotoxicity - muscle paralysis, and convulsion and loss of movement - was observed at 33.0 mg/kg group in the single dose toxicity study. Dysfunction of liver and kidney were shown in the repeated oral administration of the amanita muscaria at 3${\sim}$4 weeks. Serum chemistry results revealed a marked increase of LDH [Lactate Dehydrogenase (3181.5 IU/L; normal 230-460 IU/l)], ALT [Alanine transaminase (124.0 IU/l; normal <40 IU/l)] but the kidney was normal. Histopathological results show interstitial edema and tubular epithelial necrosis in the kidney. These results suggest that amanita muscaria has a neurotoxic effect and causes dysfunction of liver and kidney in the SD rat.

• Journal of Life Science
• /
• v.23 no.5
• /
• pp.710-720
• /
• 2013

Radiotherapy is commonly used in treating many kinds of cancers which cannot be cured by other therapeutic strategies. However, radiotherapy also induces the damages on the normal tissues. Radiation-induced fibrosis is frequently observed in the patients undergoing radiotherapy, and becomes a major obstacle in the treatment of intrahepatic cancer. Hedgehog (Hh) that is an essential in the liver formation during embryogenesis is not detected in the healthy liver, but activated and modulates the repair process in damaged livers in adult. The expression of Hh increases with the degree of liver damage, regulating the proliferation of hepatic progenitors and hepatic stellate cells (HSC). In addition, Hh induces epithelial-to-mesencymal transition (EMT) and activation of myofibroblasts. In the irradiated livers, up-regulated expression of Hh signaling was associated with proliferation of progenitors, EMT induction, and increased fibrosis. Female-specific expression of Hh leaded to the expansion of progenitors and the accumulation of collagen in the irradiated livers of female mice, indicating that gender disparity in Hh expression may be related with radiation-susceptibility in female. Hence, Hh signaling becomes a novel object of studies for fibrogenesis induced by radiation. However, the absence of the established experimental animal models showing the similar physiopathology with human liver diseases and fibrosis-favorable microenvironment hamper the studies for the radiation-induced fibrosis, providing a few descriptive results. Therefore, further research on the association of Hh with radiation-induced fibrosis can identify the cell and tissue-specific effects of Hh and provides the basic knowledge for underlying mechanisms, contributing to developing therapies for preventing the radiation-induced fibrosis.

• Journal of Life Science
• /
• v.23 no.4
• /
• pp.501-509
• /
• 2013

Formaldehyde (FA) is widely used in industries, and it is an indoor and outdoor pollutant. Exposure to FA may cause inflammation and respiratory oxidative stress. Studies have demonstrated that FA can cause cancer in animal models. During the regeneration process of injured starfish (Asterina pectinifera), several changes have been observed in the expression of cytokines. In particular, higher TGF-${\beta}1$ expression has been detected in arm cut starfish extract after eight days. The current study was designed to elucidate the in-vitro and the in-vivo pharmacological effects of starfish extract on FA exposure. We investigated the protective effects of intact starfish extract and arm cut starfish extract on an IMR-90 cell line and on mouse lung injury in response to FA exposure. In the presence of FA, inhalation of the arm cut starfish extract was associated with more promising cell proliferation, TNF-${\alpha}$, NF-${\kappa}B$ decrement, and $I{\kappa}-B{\alpha}$ increment. In the experimental group, the pulmonary structure of the arm cut starfish extract-treated group in the presence of FA exposure was similar to the control group, whereas the FA exposure group showed damage to the pulmonary structure. Moreover, the arm cut starfish extracts was more effective than the intact starfish extracts in terms of the expression of TNF-${\alpha}$, NF-${\kappa}B$, $I{\kappa}-B{\alpha}$, and surfactant protein A. The results obtained in this study demonstrate that arm cut starfish extracts are more effective in protecting pulmonary structure and function against FA exposure than intact starfish extracts.