• Molecules and Cells
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• v.47 no.3
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• pp.100033.1-100033.13
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• 2024

Considering the recent increase in the number of colorectal cancer (CRC) cases in South Korea, we aimed to clarify the molecular characteristics of CRC unique to the Korean population. To gain insights into the complexities of CRC and promote the exchange of critical data, RNA-sequencing analysis was performed to reveal the molecular mechanisms that drive the development and progression of CRC; this analysis is critical for developing effective treatment strategies. We performed RNA-sequencing analysis of CRC and adjacent normal tissue samples from 214 Korean participants (comprising a total of 381 including 169 normal and 212 tumor samples) to investigate differential gene expression between the groups. We identified 19,575 genes expressed in CRC and normal tissues, with 3,830 differentially expressed genes (DEGs) between the groups. Functional annotation analysis revealed that the upregulated DEGs were significantly enriched in pathways related to the cell cycle, DNA replication, and IL-17, whereas the downregulated DEGs were enriched in metabolic pathways. We also analyzed the relationship between clinical information and subtypes using the Consensus Molecular Subtype (CMS) classification. Furthermore, we compared groups clustered within our dataset to CMS groups and performed additional analysis of the methylation data between DEGs and CMS groups to provide comprehensive biological insights from various perspectives. Our study provides valuable insights into the molecular mechanisms underlying CRC in Korean patients and serves as a platform for identifying potential target genes for this disease. The raw data and processed results have been deposited in a public repository for further analysis and exploration.

• The Journal of Korean Society for Radiation Therapy
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• v.29 no.2
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• pp.9-17
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• 2017

Purpose: The tissue description and electron density indicated by the Computed Tomography(CT) number (also known as Hounsfield Unit) in radiotherapy are important in ensuring the accuracy of CT-based computerized radiotherapy planning. The internal metal implants, however, not only reduce the accuracy of CT number but also introduce uncertainty into tissue description, leading to development of many clinical algorithms for reducing metal artifacts. The purpose of this study was, therefore, to investigate the accuracy and the clinical applicability by analyzing date from SMART MAR (GE) used in our institution. Methode: and material: For assessment of images, the original images were obtained after forming ROIs with identical volumes by using CIRS ED phantom and inserting rods of six tissues and then non-SMART MAR and SMART MAR images were obtained and compared in terms of CT number and SD value. For determination of the difference in dose by the changes in CT number due to metal artifacts, the original images were obtained by forming PTV at two sites of CIRS ED phantom CT images with Computerized Treatment Planning (CTP system), the identical treatment plans were established for non-SMART MAR and SMART MAR images by obtaining unilateral and bilateral titanium insertion images, and mean doses, Homogeneity Index(HI), and Conformity Index(CI) for both PTVs were compared. The absorbed doses at both sites were measured by calculating the dose conversion constant (cCy/nC) from ylinder acrylic phantom, 0.125cc ionchamber, and electrometer and obtaining non-SMART MAR and SMART MAR images from images resulting from insertions of unilateral and bilateral titanium rods, and compared with point doses from CTP. Result: The results of image assessment showed that the CT number of SMART MAR images compared to those of non-SMART MAR images were more close to those of original images, and the SD decreased more in SMART compared to non-SMART ones. The results of dose determinations showed that the mean doses, HI and CI of non-SMART MAR images compared to those of SMART MAR images were more close to those of original images, however the differences did not reach statistical significance. The results of absorbed dose measurement showed that the difference between actual absorbed dose and point dose on CTP in absorbed dose were 2.69 and 3.63 % in non-SMRT MAR images, however decreased to 0.56 and 0.68 %, respectively in SMART MAR images. Conclusion: The application of SMART MAR in CT images from patients with metal implants improved quality of images, being demonstrated by improvement in accuracy of CT number and decrease in SD, therefore it is considered that this method is useful in dose calculation and forming contour between tumor and normal tissues.

• Journal of Applied Biological Chemistry
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• v.59 no.3
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• pp.179-188
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• 2016

This study is aimed to evaluate the protective effect of Gastrodiae rhizoma and steamed, dried & fermented Gastrodiae rhizoma on Lipopolysaccharide (LPS)-induced hepatic injury in the mice model. Sample was selected to GR0F0 (not processed gastrodia rhizome) and GR6F4 (fermented with Saccharomyces cerevisiae before steamed and dried 6 times) based on 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid, and High-performance liquid chromatography analysis. Mice were randomly divided into 4 groups - Normal group, vehicle group (LPS treated), GR0F0 group (fed GR0F0 before LPS treated) and GR6F4 group (fed GR6F4 before LPS treated) with 6 mice in each group. GR0F0 group and GR6F4 group were fed each extract 200 mg/kg/day during 8 days. LPS 20 mg/kg injected to the experimental groups as abdominal injection. We measured aspartate aminotransferase, alanine amino-transferase in serum. GR0F0 and GR6F4 showed a significant decrease compared to the vehicle group. As a result of measuring the ROS, GR6F4 group showed a significant reduction in both the serum and liver tissues compared to the vehicle group. GR0F0 group showed a significant reduction only in the liver tissues. Activator protein-1, cyclooxygenase-2, and Inducible nitric oxide synthase were significantly decreased GR0F0 group and GR6F4 group. But tumor necrosis factor alpha only showed a significant reduction in GR6F4 group. GR0F0 and GR6F4 groups against liver damage in mice with LPS. That showed significant effects on anti-oxidant and anti-inflammatory action. The effects of GR6F4 group showed superior results compared to GR0F0 group. Therefore, Steamed, dried & fermented Gastrodia rhizoma was might have a protective effect on liver injury.

• Applied Microscopy
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• v.32 no.4
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• pp.385-398
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• 2002

The purpose of the present study is to investigate whether stromal cells supporting specific microenvironment for hematopoiesis of bone marrow are affected by toxicants and therapeutic drugs such as antibiotics and anticancer drugs and whether laminin-1 is associated with such effects. SD rats were intraperitoneally injected with 75 mg/kg of cyclophosphamide which is widely used to treat infant's solid tumor, leukemia and myeloma and sacrificed after 3 days, 1 week, 3 weeks or 5 weeks of injection. The bone marrow extracted and paraffin-sectioned was analyzed using immunohistochemical staining. A part of tissues was subjected to electron microscopy following reaction with rabbit anti-laminin antibody, biotinylated goat anti-rabbit IgG conjugated with 12 nm gold particles, and staining with uranyl acetate. 1. The bone marrow tissue at day 3 post injection with cyclophosphamide displayed dilated venous sinus, partial necrotic death, and decreased number of hematopoietic cells. Laminin-1 was intensively stained in the reticular and adipose tissues. 2. Up to 5 weeks post injection, laminin-1 was stained at a low level in the stromal tissue of bone marrow and the number of hematopoietic cell was increased. 3. Deposition of the gold particle which represents laminin-1 expression was observed at the highest level in the stromal cells of bone marrow obtained 3 days after injection, and decreased after 1 to 5 weeks. These results suggest that stromal cells which play a role in supporting microenvironment for bone marrow hematopoiesis augment induction of laminin-1 expression and activation upon administration of cyclophosphamide.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.7
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• pp.929-937
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• 2016

The purpose of this study was to investigate the effect of Acanthopanax senticosus extract (ASE) (ethanol : DW=1:1, v/v) on inhibition of type 2 diabetes using an OLETF rat model via regulation of HbA1c and AGEs levels. Supplementation with ASE 0.1% and 0.5% effectively lowered levels of glucose, insulin, oral glucose tolerance test, and Homa-insulin resistance, suggesting reduced insulin resistance. Blood levels of HbA1c and AGEs were significantly reduced in a dose-dependent manner. As oxidative stress plays a key role in accelerating production of HbA1c and AGEs, which worsen symptoms of type 2 diabetes, levels of malonaldehyde and pro-inflammatory cytokines were measured. Lipid peroxidation in both blood and liver tissues was significantly reduced, and induction of pro-inflammatory cytokines interleukin-${\beta}$ and tumor necrosis factor-${\alpha}$, which elevate production of HbA1c and AGEs, was inhibited (P<0.05). To evaluate the possible cellular events after AGEs receptor activation, genetic expression of protein kinase C (PKC)-${\delta}$ and transforming growth factor (TGF)-${\beta}$ was measured by real-time polymerase chain reaction. Supplementation with both ASE 0.1% and 0.5% significantly inhibited mRNA expression of PKC-${\delta}$ and TGF-${\beta}$, indicating that ASE may have beneficial effects on preventing insulin-resistant cells or tissues from progressing to diabetic complications. Taken together, ASE has potential to improve type 2 diabetes by inhibiting insulin resistance and protein glycosylation, including production of HbA1c and AGEs. Anti-oxidative activities of ASE are a main requisite for reducing production of HbA1c and AGEs and are also related to regulation of the PKC signaling pathway, resulting in suppression of TGF-${\beta}$, which increases synthesis of collagen, prostaglandin, and disease-related proteins.

• Journal of the Korean Society of Radiology
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• v.15 no.7
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• pp.965-973
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• 2021

Since radiation therapy is irradiated with high-energy X-rays in a variety of at least 20 Gy to 80 Gy, a high dose is administered to the local area where the tumor is located, and various side effects of some normal tissues are expected. Currently, in clinical practice, lead, a representative material, is used as an effort to shield normal tissues, but lead is classified as a heavy metal harmful to the human body, and a large amount of skin contact can cause poisoning. Therefore, this study intends to manufacture a measurement sheet that can compensate for the limitations of lead using the materials Tungsten, Brass, and Copper of the 3D printer of the FDM (Fused Deposition Modeling) method and to investigate the penetration performance. Tungsten mixed filament transmission measurement sheet size was 70 × 70 mm and thickness 1, 2, 4 mm using a 3D printer, and a linear accelerator (TrueBeam STx, S/N: 1187) was measured by irradiating 100 MU at SSD 100 cm and 5 cm in water using a water phantom, an ion chamber (FC-65G), and an elcetrometer (PTW UNIDOSE), and the permeability was evaluated. As a result of increasing the measurement sheet of each material by 1 mm, in the case of Tungsten sheet at 3.8 to 3.9 cm in 6 MV, the thickness of the lead shielding body was thinner than 6.5 cm, and in case of Tungsten sheet at 4.5 to 4.6 cm in 15 MV. The sheet was thinner than the existing lead shielding body thickness of 7 cm, and equivalent performance was confirmed. Through this study, the transmittance measurement sheet produced using Tungsten alloy filaments confirmed the possibility of transmission shielding in the high energy region. It has been confirmed that the usability as a substitute is also excellent. It is thought that it can be provided as basic data for the production of shielding agents with 3D printing technology in the future.

• Radiation Oncology Journal
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• v.22 no.4
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• pp.237-246
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• 2004

Purpose: To investigate the effects of radiation dose-escalation on the treatment outcome, complications and the other prognostic variables for glioblastoma patients treated with 3D-conformal radiotherapy (3D-CRT). Materials and Methods: Between Jan 1997 and July 2002, a total of 75 patients with histologically proven diagnosis of glioblastoma were analyzed. The patients who had a Karnofsky Performance Score (KPS) of 60 or higher, and received at least 50 Gy of radiation to the tumor bed were eligible. All the patients were divided into two arms; Arm 1, the high-dose group was enrolled prospectively, and Arm 2, the low-dose group served as a retrospective control. Arm 1 patients received $63\~70$ Gy (Median 66 Gy, fraction size $1.8\~2$ Gy) with 3D-conformal radiotherapy, and Arm 2 received 59.4 Gy or less (Median 59.4 Gy, fraction size 1.8 Gy) with 2D-conventional radiotherapy. The Gross Tumor Volume (GTV) was defined by the surgical margin and the residual gross tumor on a contrast enhanced MRI. Surrounding edema was not included in the Clinical Target Volume (CTV) in Arm 1, so as to reduce the risk of late radiation associated complications; whereas as in Arm 2 it was included. The overall survival and progression free survival times were calculated from the date of surgery using the Kaplan-Meier method. The time to progression was measured with serial neurologic examinations and MRI or CT scans after RT completion. Acute and late toxicities were evaluated using the Radiation Therapy Oncology Group neurotoxicity scores. Results: During the relatively short follow up period of 14 months, the median overall survival and progression free survival times were $15{\pm}1.65$ and $11{\pm}0.95$ months, respectively. The was a significantly longer survival time for the Arm 1 patients compared to those in Arm 2 (p=0.028). For Arm 1 patients, the median survival and progression free survival times were $21{\pm}5.03$ and $12{\pm}1.59$ months, respectively, while for Arm 2 patients they were $14{\pm}0.94$ and $10{\pm}1.63$ months, respectively. Especially in terms of the 2-year survival rate, the high-dose group showed a much better survival time than the low-dose group; $44.7\%$ versus $19.2\%$. Upon univariate analyses, age, performance status, location of tumor, extent of surgery, tumor volume and radiation dose group were significant factors for survival. Multivariate analyses confirmed that the impact of radiation dose on survival was independent of age, performance status, extent of surgery and target volume. During the follow-up period, complications related directly with radiation, such as radionecrosis, has not been identified. Conclusion: Using 3D-conformal radiotherapy, which is able to reduce the radiation dose to normal tissues compared to 2D-conventional treatment, up to 70 Gy of radiation could be delivered to the GTV without significant toxicity. As an approach to intensify local treatment, the radiation dose escalation through 3D-CRT can be expected to increase the overall and progression free survival times for patients with glioblastomas.

• The Journal of the Korean bone and joint tumor society
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• v.6 no.1
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• pp.22-29
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• 2000

Purpose : The purpose of the current study was to report the results of curettage and en bloc excision as well as to introduce how to excise the nidus percutaneously with Halo-mill. Material and Methods : Twenty patients(14 men and 6 women) were evaluated, who had operative treatments after diagnosed as osteoid osteoma from March 1990 to January 1998. These patients ranged in age from 7 to 42 years(average: 20.8 years). Locations were 9 femurs, 6 tibias, 2 vertebras, 1 ulna, 1 maxilla and 1 skull. Nine femoral lesions included 5 proximal metaphysis, 2 neck and 2 diaphysis, while 5 tibial lesions included 3 diaphysis, 1 proximal metaphysis and 1 distal metaphysis. We used simple radiography, bone scan, CT and MRI for the accurate diagnosis and localization. As for surgical treatments, while excision and curettage had to need open-exposure of lesion, the percutaneous excision of nidus did not need openexposure : guided Halo-mill into K-wire inserted to nidus under image intensifier. Results : Simple radiography showed that 10 cases had typical nidus and others had only cortical sclerosis. Bone scan was performed at 14 cases and all had hot uptake except one case. We used CT in 10 cases and MRI in 4 cases as diagnostic methods, of which 1 case didn't reveal nidus at CT. Surgical treatment consisted of 6 curettages, 11 excisions, 2 percutaneous excisions with halo-mill and 1 total elbow arthroplasty. We used 7mm sized Halo-mill. During the follow-up period, all patient relieved symptoms and there were no recurrences. All had histologically typical findings except one which had hyperostosis without nidus. Conclusion : Complete removal of the nidus is the most important factor in the treatment. We could excise the nidus percutaneously in 2 cases with the minimal injury to surrounding soft tissues. If we could evaluate the precise location, size of nidus and percutaneous acccesibility, the percutaneous excision of nidus with Halo-mill could be an alternative method as a treatment of osteoid osteoma.

• Journal of Life Science
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• v.21 no.5
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• pp.631-646
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• 2011

Mesenchymal stem cells (MSC) are multipotent and can be isolated from diverse human tissues including bone marrow, fat, placenta, dental pulp, synovium, tonsil, and the thymus. They function as regulators of tissue homeostasis. Because of their various advantages such as plasticity, easy isolation and manipulation, chemotaxis to cancer, and immune regulatory function, MSCs have been considered to be a potent cell source for regenerative medicine, cancer treatment and other cell based therapy such as GVHD. However, relating to its supportive feature for surrounding cell and tissue, it has been frequently reported that MSCs accelerate tumor growth by modulating cancer microenvironment through promoting angiogenesis, secreting growth factors, and suppressing anti-tumorigenic immune reaction. Thus, clinical application of MSCs has been limited. To understand the underlying mechanism which modulates MSCs to function as tumor supportive cells, we co-cultured human adipose tissue derived mesenchymal stem cells (ASC) with cancer cell lines H460 and U87MG. Then, expression data of ASCs co-cultured with cancer cells and cultured alone were obtained via microarray. Comparative expression analysis was carried out using DAVID (Database for Annotation, Visualization and Integrated Discovery) and PANTHER (Protein ANalysis THrough Evolutionary Relationships) in divers aspects including biological process, molecular function, cellular component, protein class, disease, tissue expression, and signal pathway. We found that cancer cells alter the expression profile of MSCs to cancer associated fibroblast like cells by modulating its energy metabolism, stemness, cell structure components, and paracrine effect in a variety of levels. These findings will improve the clinical efficacy and safety of MSCs based cell therapy.

• Tuberculosis and Respiratory Diseases
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• v.45 no.3
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• pp.587-595
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• 1998

Background: Recombinant adenovirus hold promise as vectors to carry therapeutic genes for several reasons: 1) they can infect both dividing and non-dividing cells; 2) they have the ability to directly transduce tissues in vivo; 3) they can easily be produced in high titer; and 4) they have an established record of safety as vaccination material. However, one of the major limitation in the use of adenoviruses is that transgene expression is quite short because adenovirusees insert their DNA genome episomally rather than by chromosomal integration, and an immune response against the virus destroys cells expressing the therapeutic gene. Since sodium butyrate has been reported to induce adenovirus-mediated gene expression, we hypothesized that treatment of tumor cells, transduced with herpes simples virus thymidine kinase(HSVtk) gene using adenoviral vector, with butyrate could augment the effect of gene therapy. Methods: We transduced HSVtk gene, driven by the cytomegalovirus promoter, into REN cell line(human mesothelioma cell line). Before proceeding with the comparison of HSVtk/ganciclovir mediated bystander killing, we evaluated the effect of butyrate on the growth of tumor cells in order to rule out a potential antitumor effect of butyrate alone, and also on expression of HSVtk gene by Western blot analysis. Then we determined the effects of butyrate on bystander-mediated cell killing in vitro. Results: There was no inhibition of growth of cells exposed to butyrate for 24 hours at a concentration of 1.5mM/L. Toxic effects were seen when the concentration of butyrate was greater than 2.0mM/L. Gene expression was more stable and bystander effect was augmented by butyrate treatment of a concentration of 1.5mM/L. Conclusion: These results provide evidence that butyrate can augment the efficiency of cell killing with HSVtk/GCV system by inducing transgene expression and may thus by a promising new approach to improve responses in gene therapy using adenoviral vectors.