• The Korean Journal of Nuclear Medicine
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• v.27 no.1
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• pp.118-122
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• 1993

To evaluate the genotoxic effect of $^{131}I$, lymphocytes from 9 patients who underwent large dose (150 mCi) $^{131}I$ therapy after total thyroidectomy were studied for sister chromatid exchanges (SCE) before and after their first radioiodine treatments. Frequency of SCE (FSCE) was counted in chromosomes of 30 lymphocytes in each patients, and was expressed as numbers of SCE per cell. Numbers of leukocytes were also observed during $^{131}I$ therapy. Pretreatment FSCE ($4.2{\pm}0.7$) was not different from the control ($3.8{\pm}0.4$, p=0.17). However, the frequency was significantly elevated after $^{131}I$ administration (at the second day, $7.9{\pm}0.8$, p<0.001) and was diminished but still significantly elevated after a week (at 9th day, $6.4{\pm}0.6$, p<0.001). While counts of leukocytes in the peripheral blood showed no change (p> 0.05). In conclusion, chromatids of human lymphocytes were significantly damaged after $^{131}I$ treatment without any bone marrow supression. And the repair of SCE was not complete within one week.

• Journal of Life Science
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• v.26 no.1
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• pp.91-100
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• 2016

Angiogenesis is essential for the pathophysiological processes of embryogenesis, tissue growth, diabetic retinopathy, psoriasis, wound healing, rheumatoid arthritis, cardiovascular diseases, and tumor growth. Inhibition of angiogenesis represents an attractive therapeutic approach for the treatment of angiogenic diseases such as cancer. However, uncontrolled angiogenesis is also necessary for tumor development and metastasis. Inhibition of vascular endothelial growth factor (VEGF) signaling, a critical factor in the induction of angiogenesis, cause robust and rapid changes in blood vessels of tumors and therefore VEGF constitutes a target for such anti-angiogenic therapy. Recently, since natural compounds pose significantly less risk of deleterious side effects than synthetic compounds, a great many natural resources have been assessed for useful substance for anti-angiogenic treatment. Here we evaluated the anti-angiogenic effects of a hot water extract of Scutellaria baicalensis (SBHWE) using in vitro assays and ex vivo animal experiments. Our results show that SBHWE dose-dependently abrogated vascular endothelial responses by inhibiting VEGF-stimulated migration and invasion as well as tube formation in a human umbilical vein endothelial cell (HUVEC) model, without cytotoxicity, as determined by a cell viability assay. Further study revealed that SBHWE prevented VEGF-induced neo-vascularization in a rat aortic ring sprouting model. Taken together, our findings reveal an anti-angiogenic activity of Scutellaria baicalensis and suggest that SBHWE is a novel candidate inhibitor of VEGF-induced angiogenesis.

• Journal of Periodontal and Implant Science
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• v.36 no.3
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• pp.783-796
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• 2006

The periodontium is a topographically complex organ consisting of epithelial tissue, soft and mineralized tissues. Structures comprising the periodontium include the gingiva, periodontal ligament (PDL) , cementum and the alveolar bone. The molecular mechanism of differentiation in PDL fibroblast cells remain unclear. Amino acid transporters play an important role in supplying nutrition to normal and cancer cells and for cell proliferation. Amino acid transport system L is a major nutrient transport system responsible for the Na+-independent transport of neutral amino acids including several essential amino acids. The system L is divided into two major subgroups, the L-type amino acid transporter 1 (LAT1) and the L-type amino acid transporter 2 (LAT2). In this study, the expression pattern of amino acid transport system L was, therefore, investigated in the differentiation of PDL fibroblast cells. To determine the expression level of amino acid transport system L participating in intracellular transport of amino acids in the differentiation of PDL fibroblast cells, it was examined by RT-PCR, observation of cell morphology, Alizaline red-S staining and uptake analysis after inducing experimental differentiation in PDL fibroblast cells isolated from mouse molar teeth. The results are as follows. 1. The LAT1 mRNA was expressed in the early stage of PDL fibroblast cell differentiation. This expression level was gradually reduced by differentiation- inducing time and it was not observed after the late stage. 2. The expression level of LAT2 mRNA was increased in time-dependent manner during differentiation induction of PDL fibroblast cells. 3. There was no changes in. the expression level of 4F2hc mRNA, the cofactor of LAT1 and LAT2, during differentiation of PDL fibroblast cells. 4. The expression level of ALP mRNA was gradually increased and the expression level of Col I mRNA was decreased during differentiation of PDL fibroblast cells. 5. The L-leucine transport was reduced by time from the early stage to the late stage in PDL fibroblast cell differentiation. As the results, it is considered that among neutral ammo acid transport system L in differentiation of PDL fibroblast cells, the LATl has a key role in cell proliferation in the early stage of cell differentiation and the LAT2 has an important role in the late stage of cell differentiation for providing cells with neutral amino acids including several essential amino acids.

• Tuberculosis and Respiratory Diseases
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• v.53 no.2
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• pp.196-201
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• 2002

Malignant melanoma is a highly malignant form of cutaneous cancer derived from melanocytes. The lesion frequently metastasizes to the lymph nodes, lung, liver and bone. However, an endobronchial metastasis and a primary malignant. melanoma of the lung are quite rare. We report a case of an unknown primary malignant melanoma with a pulmonary and endobronchial metastasis in a 34 years old male. He complained of coughing and black-colored sputum. Abnormal skin and mucosal lesions were not found during a physical examination. A chest X-ray revealed multiple nodular masses in both lung fields. A flexible bronchoscopy showed two yellowish small nodules at the entry of left lower bronchus. Vimentin, the S-100 protein, and HMB-45 stain positive melanoma cells were detected at the bronchoscopic biopsy specimen.

• Journal of Life Science
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• v.21 no.12
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• pp.1778-1783
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• 2011

Hematopoietic cytokines regulate production of blood cells by stimulating proliferation and differentiation of bone marrow cells. Among these hematopoietic cytokines, called hematopoitic growth factors, glranulocyte-colony stimulating Factor (G-CSF), which regulates growth of neutrophils, is one of important therapeutic factors because cancer patients suffer with neutropenia which is severe reduction of neutrophils after chemotherapy. Two groups of recombinant G-CSF have approved and used for therapeutic purposes and many researches are still on-going to produce recombinant G-CSF by different techniques. We engineered human G-CSF with Bombyx specific endoplasmic reticulum (ER) signal sequence, therefore, secretion of human G-CSF protein was improved in Bombyx mori-origined cell line, Bm5. The Bombyx ER signal sequence and human G-CSF matured protein region chimera was further remodeled at the N-terminus of matured G-CSF protein to understand roles of N-terminus on outer cellular secretion and/or production. Three different mutants were generated deleting three amino acids in non alpha-helical region in N-terminus in order to scan important amino acids for G-CSF secretion. One of 3 different N-terminal deletion mutants showed dramatically reduction of secreted amount of G-CSF indicating its important role on secretion. The data suggest that remodeling in non alpha-helical region of N-terminus is also important for recombinant G-CSF production.

• The Journal of the Korean bone and joint tumor society
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• v.15 no.1
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• pp.26-33
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• 2009

Purpose: This study was performed to investigate the maspin gene expression from osteosarcoma and to determine whether its expression correlates with clinical course of the cancer. Materials and Methods: Between 2001 and 2006, 39 patients who were diagnosed and treated surgically for osteosarcoma were included in the present study. We estimated the maspin gene expression from osteosarcoma tissue samples using RT-PCR. And we examined the correlations between the maspin expression and clinical data (post-chemotherapeutic response, local relapse or metastases). Results: Maspin was over expressed in 21 cases of 39 osteosarcoma tissues. There were significant correlations between maspin expression and the response to neoadjuvant chemotherapy, distant metastases & metastasis-free survival. In multivariate analysis, maspin low-expression was significant risk factor for distant metastases. Also, there was significant difference in metastasis-free survivals between maspin hi- expression group ($69.0{\pm}10.5%$) and low-expression group ($25.4{\pm}13.0%$). Conclusion: The degree of maspin expression in osteosarcoma was significant risk factor for distant metastases and predictive factor for metastasis-free of overall survivals. Maspin may be a useful biologic marker in evaluating the prognosis in patients with osteosarcoma and could be used as a therapeutic target clinically.

• Journal of Korean Medical Science
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• v.33 no.51
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• pp.325.1-325.10
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• 2018

Background: To evaluate survival outcomes and prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) who received sunitinib (SU) and pazopanib (PZ) as first-line therapy in real-world Korean clinical practice. Methods: Data of 554 patients with mRCC who received SU or PZ at eight institutions between 2012 and 2016 were retrospectively reviewed. Based on the targeted therapy, the patients were divided into SU (n = 293) or PZ (n = 261) groups, and the clinicopathological variables and survival rates of the two groups were compared. A multivariable Cox proportional hazard model was used to determine the prognostic factors for OS. Results: The median follow-up was 16.4 months (interquartile range, 8.3-31.3). Patients in the PZ group were older, and no significant difference was observed in the performance status (PS) between the two groups. In the SU group, the dose reduction rate was higher and the incidence of grade 3 toxicity was more frequent. The objective response rates were comparable between the two groups (SU, 32.1% vs. PZ, 36.4%). OS did not differ significantly between the two groups (SU, 36.5 months vs. PZ, 40.2 months; log-rank, P = 0.955). Body mass index, Eastern Cooperative Oncology Group PS > 2, synchronous metastasis, poor Heng risk criteria, and liver and bone metastases were associated with a shorter OS. Conclusion: Our real-world data of Korean patients with mRCC suggested that SU and PZ had similar efficacies as first-line therapy for mRCC. However, PZ was better tolerated than SU in Korean patients.

• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.166-174
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• 2021

Multiple myeloma is a malignant cancer of plasma cells. Despite recent progress with immunomodulatory drugs and proteasome inhibitors, it remains an incurable disease that requires other strategies to overcome its recurrence and non-response. Based on the high expression levels of programmed death-ligand 1 (PD-L1) in human multiple myeloma isolated from bone marrow and the murine myeloma cell lines, NS-1 and MOPC-315, we propose PD-L1 molecule as a target of anti-multiple myeloma therapy. We developed a novel anti-PD-L1 antibody containing a murine immunoglobulin G subclass 2a (IgG2a) fragment crystallizable (Fc) domain that can induce antibody-dependent cellular cytotoxicity. The newly developed anti-PD-L1 antibody showed significant antitumor effects against multiple myeloma in mice subcutaneously, intraperitoneally, or intravenously inoculated with NS-1 and MOPC-315 cells. The anti-PD-L1 effects on multiple myeloma may be related to a decrease in the immunosuppressive myeloid-derived suppressor cells (MDSCs), but there were no changes in the splenic MDSCs after combined treatment with lenalidomide and the anti-PD-L1 antibody. Interestingly, the newly developed anti-PD-L1 antibody can induce antibody-dependent cellular cytotoxicity in the myeloma cells, which differs from the existing anti-PD-L1 antibodies. Collectively, we have developed a new anti-PD-L1 antibody that binds to mouse and human PD-L1 and demonstrated the antitumor effects of the antibody in several syngeneic murine myeloma models. Thus, PD-L1 is a promising target to treat multiple myeloma, and the novel anti-PD-L1 antibody may be an effective anti-myeloma drug via antibody-dependent cellular cytotoxicity effects.

• The Journal of the Korean bone and joint tumor society
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• v.17 no.2
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• pp.79-86
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• 2011

Purpose: Modular tumor prosthesis is the most popular recontructive modality after resection of malignat tumor in extremity. Complications and survival of tumor prosthesis reconstruction are well-known. however, reports on the long-term outcome of tumor prosthesis in osteosarcoma patientss are scarece. Materials and Methods: In 158 cases as diagnosed as osteosarcoma from feburary 1989 to December 2006 in a single cancer center. We retrospectively reviewd 48 osteosarcoma patients who under went tumor prosthetic reconstruction. Mean follow up preiod was 75.6 months (range; 60 to 179 months). There were 28 males, 20 females and mean age was 22.4 years (range; 11-71). Pathologic subtypes were conventional central osteosarcoma in 46 cases and periosteal in 2 cases. The location of the tumor was proximal tibia (26 cases), distal femor (20 cases), femor diaphysis (1 case), and tibia diaphysis (1 case). In 41 cases built-up-type tumor prosthesis have been used and 7 cases expansion-type tumor prosthesis have been used. We used Musculoskeletal tumor society (MSTS) grading system to asses post operation function, and we analyzed survival rate of patient and tumor prosthesis and complication. Results: The overall survival rate was 77.7% and disease free survival rate was 68.9%. The survival rate of tumor prosthesis was 73%, in last follow up tumor prosthesis has been removed in 12 cases. All of them, 17 complications occurred, which included infection in 16 cases, Periprosthetic Fracture and Loosening of tumor prosthesis in 4 cases, articular instability in 4 cases. MSTS functional score was 74.1% in post operation. Conclusion: In long term follow up result, Primary tumor prosthesis -a reconstruction method after a wide extensional resecion of a bone tumor- can be a effective treatment method in asepect of survival rate, functional assesment and complication.

• The Journal of Korean Society for Radiation Therapy
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• v.16 no.1
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• pp.57-65
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• 2004

Introduction : The phantom that includes high density materials such as steel was custom-made to fix lung and bone in order to evaluation inhomogeneity correction at the time of conducting radiation therapy to treat lung cancer. Using this, values resulting from the inhomogeneous correction algorithm are compared on the 2 and 3 dimensional radiation therapy planning systems. Moreover, change in dose calculation was evaluated according to inhomogeneous by comparing with the actual measurement. Materials and Methods : As for the image acquisition, inhomogeneous correction phantom(Pig's vertebra, steel(8.21g/cm3), cork(0.23 g/cm3)) that was custom-made and the CT(Volume zoom, Siemens, Germany) were used. As for the radiation therapy planning system, Marks Plan(2D) and XiO(CMS, USA, 3D) were used. To compare with the measurement value, linear accelerator(CL/1800, Varian, USA) and ion chamber were used. Image, obtained from the CT was used to obtain point dose and dose distribution from the region of interest (ROI) while on the radiation therapy planning device. After measurement was conducted under the same conditions, value on the treatment planning device and measured value were subjected to comparison and analysis. And difference between the resulting for the evaluation on the use (or non-use) of inhomogeneity correction algorithm, and diverse inhomogeneity correction algorithm that is included in the radiation therapy planning device was compared as well. Results : As result of comparing the results of measurement value on the region of interest within the inhomogeneity correction phantom and the value that resulted from the homogeneous and inhomogeneous correction, gained from the therapy planning device, margin of error of the measurement value and inhomogeneous correction value at the location 1 of the lung showed $0.8\%$ on 2D and $0.5\%$ on 3D. Margin of error of the measurement value and inhomogeneous correction value at the location 1 of the steel showed $12\%$ on 2D and $5\%$ on 3D, however, it is possible to see that the value that is not correction and the margin of error of the measurement value stand at $16\%$ and $14\%$, respectively. Moreover, values of the 3D showed lower margin of error compared to 2D. Conclusion : Revision according to the density of tissue must be executed during radiation therapy planning. To ensure a more accurate planning, use of 3D planning system is recommended more so than the 2D Planning system to ensure a more accurate revision on the therapy plan. Moreover, 3D Planning system needs to select and use the most accurate and appropriate inhomogeneous correction algorithm through actual measurement. In addition, comparison and analysis through TLD or film dosimetry are needed.