• The Journal of the Korean bone and joint tumor society
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• v.20 no.1
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• pp.1-6
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• 2014

Purpose: To examine the expression of Connective Tissue Growth Factor (CTGF) in osteosarcoma and to evaluate its role in osteosarcoma invasion and proliferation. Materials and Methods: The mRNA expression of CTGF from 23 patient-derived osteosarcoma cell lines was examined, and the role of CTGF in cell invasion and proliferation was examined using siRNA transfection. Results: The over-expression of CTGF mRNA was observed in 17 cell lines (74%). CTGF-specific siRNA transfection into SaOS-2 and MG63 cell lines resulted in efficient knockdown of CTGF expression on Western blot analysis. siRNA transfected cells showed decreased migration on Matrigel invasion assay and decreased cell proliferation on WST-1 assay. Conclusion: These results indicated that the CTGF expression may play an important role in osteosarcoma progression, and may be a therapeutic target of osteosarcoma.

• The Journal of the Korean bone and joint tumor society
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• v.11 no.1
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• pp.46-53
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• 2005

Purpose: Bisphosphonates (BPs) are the analogues of endogenous pyrophosphates: they have been used in the treatment of skeletal diseases such as Paget's disease, osteoporosis, and tumorinducing ostelysis, and are used in treatment of osteolytic metastasis of breast cancer recently. They are also used as one of the therapeutic agents for metastasis of prostatic cancer of which metastasis makes the mixed nature of osteolysis and ostegenesis. Although the action mechanism of BPs are well known for diseases with excessive osteoclastic bone resorption, the direct effect of BPs has not been known yet. This study was intended to see the tumor suppression capability of Zoledronic acid(ZOL) using nude mouse with osteosarcoma. Materials and Methods: MG-63 and HOS osteosarcoma cell lines were used and the transforemed MG-63-GFP and HOS-GFP cells, which were made for detection under fluorescent light, were subcutaneously injected to make osteosarcoma. The five 6-week male mice were used for the experiment at each group. After the injection, mice were cultivated until tumor pieces grow up to $3{\times}3{\times}3$ $mm^3$ and ZOL of 120 ug/kg was subcutaneously injected twice a week. Sizes of tumor were measured twice a week and photographed under fluorescent light. Results: In in vivo test with HOS osteosarcoma cell lines, mean size of tumors was 2,520 $mm^3$ in control group and was 131 $mm^3$ in ZOL group, which showed 94% of reduction comparing with the control ; with MG-63 osteosarcoma cell lines, mean size of tumors was 2,866 $mm^3$ in control group and was 209 $mm^3$ in test group with 72% of reduction (p<0.05). Conclusion: In in vivo tests with nude mice, we suggest that ZOL has direct effect on osteosarcoma cells and it would be used as one of the therapeutic agents for osteosarcoma, especially to ZOL-sensitive osteosarcoma cells.

• Journal of Acupuncture Research
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• v.20 no.3
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• pp.63-74
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• 2003

목적 : 한의학에서 관절염이나 진통치료에 사용되어 왔던 봉독약침액이 인간 골육종 세포주인 MG-63 세포에서 항종양효과가 있는지 연구하고자 한다. 특히 본 실험에서는 이러한 봉독의 종양발생 억제작용이 세포사멸과 관련이 있는지, 그리고 프로스타글란딘 합성 효소인 cyclooxygenase(COX)-2의 억제와 관련이 있는지를 연구하고자 한다. 방법 : 인간 골육종 세포주에서 세포사멸의 변화를 관찰하기 위해서 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium brimide(MTT) assay, 4,6-diamidino-2-phenylindole (DAPI), DNA fragmentation assay 및 reverse transcription-polymerase chain reaction(RT-PCR) 방법을 이용하였다. 결과 : 세포독성 검사에서 봉독은 MG-63 세포에서 농도-의존적으로 세포독성을 나타내었다. 이러한 봉독의 세포독성이 세포사멸로 인한 것인지를 여러 가지 형태로 검사한 결과 봉독에 의한 세포독성은 TUNEL 검사와 DAPI 염색시 세포사멸의 특징적인 소견들을 나타내었고, flow cytometric 분석에서도 세포사멸을 의미하는 세포주기의 변화들을 나타내었다. 봉독이 COX-2의 발현에 미치는 영향을 RT-PCR로 실험한 결과 봉독은 COX-2 mRNA의 발현을 선택적으로 억제하였다. 결론 : 본 실험의 결과 봉독은 COX-2 mRNA의 발현을 억제함으로써 골육종 세포에서 세포사멸을 유발하고 그 결과 항종양효과를 나타내는 것으로 보여진다.

• The Journal of the Korean bone and joint tumor society
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• v.13 no.2
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• pp.88-95
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• 2007

Purpose: The purpose of this study was to compare the proapoptotic effects of matrix metal-loproteinase inhibitor (MMPI) and doxorubicin on wild-type p53 osteosarcoma cell line, socalled U2OS cell line. Materials and Methods: U2OS cells were treated with MMP inhibitor III (MMPI III) and doxorubicin, either respectively or simultaneously. In cells treated with doxorubicin, Fas-neutralizing antibody so called ZB4 was additionally treated to examine whether the doxorubicin played a role through the Fas/FasL pathway. Cells were analysed regarding to apoptosis and cell death by flow cytometry. Results: U2OS cells incubated with doxorubicin showed significant amount of cell death in dose-dependent manner. However, those incubated with MMPI III mostly remained viable state. In addition, there is no relationship between two drugs. Cells treated with doxorubicin and ZB4 at the same time did not show down regulation of apoptosis through inhibition of Fas/FasL pathway. Conclusion: It is important to re-examine MMP inhibitor's effect on other osteosarcoma cell line with wild-type p14 as well as wild-type p53 to evaluate its proapoptotic effect.

• The Journal of the Korean bone and joint tumor society
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• v.13 no.2
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• pp.167-172
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• 2007

Malignant transformation of giant cell tumor (GCT) is known to be rare. Most of malignant transformation is reported to occur after radiation and malignant transformation without prior radiation is extremly rare. Both radiographic and pathologic findings are confusing to make a correct diagnosis. Due to the poor prognosis, early aggressive treatment is mandatory. We report this rare case together with the review of the literature.

• The Journal of the Korean bone and joint tumor society
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• v.17 no.1
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• pp.23-29
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• 2011

Purpose: We investigated the effects of phosphatase and tensin homologue deleted on chromosome 10 gene phosphatase and tensin homologue deleted on chromosome 10 gene (PTEN) expression on the cell proliferation and on the responsiveness of troglitazone in osteosarcoma cells. Materials and Methods: Western blotting alnalysis was performed to detect the expression of PTEN in U-2OS cells treated with troglitazone. WST (water-soluble tetrazolium) assay was used to evaluate cell proliferation. Flow cytometry was used to determine cell apoptosis. Further, transfection of wild-type PTEN plasmid DNA was used to upregulate PTEN expression. Results: Troglitazone treatment induced growth inhibition of U2-OS cells in a dose- and time-dependent manner. Troglitazone increased the expression of PTEN in a dose-dependent manner. PTEN upregulation induced by troglitazone treatment resulted in cell growth inhibition and apoptosis in U-2OS cells. PTEN over-expression by plasmid transfection enhanced these effects of troglitazone. Moreover, no changes were observed in the mutant type-PTEN group. Conclusion: Upregulation of PTEN is involved in the inhibition of cell growth and induction of cell apoptosis by troglitazone. Further, PTEN over-expression can cause cell growth inhibition in osteosarcoma cells and these cell growth inhibitions could be enhance by troglitazone treatment.

• Journal of Yeungnam Medical Science
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• v.16 no.2
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• pp.364-368
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• 1999

A rare case of telangiectatic osteosarcoma of the sphenoid bone was reported. The patient was a 27-year-old male and had suffered from left eye protrusion and diplopia for three months. Radiologically, a lobulated osteolytic lesion was located between sphenoid and left temporal bone. Pathologically, the tumor had multiloculated blood filled cystic vascular spaces and osteoid formation by malignant spindle osteoblast cells. The differential diagnosis of this rare entity from aneurysmal bone cyst was important radiologically and pathologically. This case is the second case of telangiectatic osteosarcoma of the sphenoid bone followed by a case of Whitehead RE and Melhem ER in 1998.

• The Journal of the Korean bone and joint tumor society
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• v.15 no.2
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• pp.111-121
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• 2009

Background: Osteosarcoma is one of the most common primary malignant tumors of bone occurring mainly in children and adolescents. Although surgery combined with chemotherapy has markedly improved patient survival during the last years, the use of anticancer drugs is still associated with serious problem, such as the frequent acquisition of drug-resistant phenotypes and occurrence of "secondary malignancies". Several solid tumors display enhanced expression of matrix metalloproteinases (MMPs), and recently clinical trials have been initiated on MMP-inhibitors. On the other hand, bisphosphonates (BPs) are inhibitors of bone resorption, and widely used to treat osteoclast-mediated bone diseases. Also they appear to possess direct antitumor activity. Methods: One osteosarcoma cell line (U2OS) was treated with ibandronate (0, 0.1, 1, $10{\mu}M$) for 48 hours. Cell viabilities were determined using MTT assay, the mRNA levels of MMP-2 and MT1-MMP were detected by reverse-transcription polymerase chain reaction, the amount of MMP-2 and MT1-MMP protein were measured by Westernblot, the activities of MMP-2 were observed by Gelatin zymography, and Matrigel invasion assays were used to investigate the invasive potential of osteosarcoma cell lines before and after ibandronate treatment. Results: The invasiveness of U2OS cell line was reduced dose-dependently following 48 hour treatment of up to $10{\mu}M$ of the ibandronate at which concentration no cytotoxicity occurred. Furthermore, the gelatinolytic activities and protein and mRNA levels of MMP-2 and MT1-MMP were also suppressed by increasing ibandronate concentrations. Conclusion: Given that MMP-2 is instrumental in tumor cell invasion, it is very likely that the reduction in osteosarcoma cell invasion by ibandronate is a consequence, at least in part, of suppressed expression of both MMP-2 and MT1-MMP. Isolation of a molecule (s) responsible for the bisphosphonate inhibition of tumor cell invasion would pave the way for the development of a new generation of metastasis inhibitors.

• The Journal of the Korean bone and joint tumor society
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• v.20 no.2
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• pp.47-53
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• 2014

Purpose: We analyzed the diagnosis and the treatment outcomes of patients with central low grade osteosarcoma. Materials and Methods: We retrospectively reviewed 16 patients with central low grade osteosarcoma were treated at out institution between 1994 and 2011. Results: There were 4 men and 12 women with mean age of 26 years. Eleven patients were correctly diagnosed but 5 patients were misdiagnosed as osteoid osteoma, non ossifying fibroma, aneurysmal bone cyst, desmoplastic fibroma. 15 patients finally received wide margin en bloc excision and one of them treated under neoadjuvant chemotherapy. Final survival status was continuous disease free in 14 and 1 patient died of renal cell cancer. Remaining 1 with multifocal lesions is alive with disease for 7 years only treated radiation therapy on residual tumors. Nine (56%) of 16 tumors showed extra-osseous extension of tumor (56%) and 1 of them showed extra-compartmental tumors. Conclusion: The diagnosis of central low grade osteosarcoma is challenging, however, considering of the clinical suspicion, the typical findings of radiologic and pathologic features, proper diagnosis is needed. This tumor should be treated with wide excision, even after an intralesional excision, to avoid local recurrence or transformation to higher histologic grade.

• Journal of Life Science
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• v.26 no.2
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• pp.147-154
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• 2016

Osteosarcoma (OS) is the most common and malignant bone tumors. Although many types of resection surgery and experimental agents were developed, median survival and clinical prognosis are poorly investigated. Recently, several researches have reported that Eucheuma cottonii has potent as protective effects of coal dust-induced lung damage via inhibition of malondialdehyde (MDA) and oxidative stress in bronchoalveolar lavage fluids (BALF). However, anti-cancer effects and specific molecular mechanism of extract from Eucheuma cottonii (EE) has not been clearly studied yet. This study evaluated that anti-cancer potential of EE in human osteosarcoma Saos-2 cells. EE indicated cytotoxicity on Saos-2 cells in a dose-dependent manner. Morphological degradation and nucleic condensation were also observed under the EE treatment. However, it did not significantly affect on non-cancerous kidney HEK-293 cells under the same concentration which is shown cytotoxicity on Saos-2 cells. The phosphorylation of Fas-Associated Death Domain (FADD) and expression of cleaved caspase-8, -7 and -3 were upregulated in a dose-dependent manner. In immunofluorescence staining, expression level of Fas and cleaved PARP were upregulated by EE treatment. Furthermore, treatment of EE induces upregulation of sub G1 phase by flow cytometry analysis. The results demonstrated that EE has a therapeutic potential against osteosarcoma via FADD mediated caspase cascade apoptosis signal pathway.