• 대한골관절종양학회지
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• 제13권2호
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• pp.88-95
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• 2007

목적: wild-type p53 단백질을 가지고 있는 U2OS 인간 골육종 세포주의 세포자멸사에서 MMP억제제와 doxorubicin의 작용을 비교하고자 하였다. 대상 및 방법: 배양한U2OS 세포주에 Doxorubicin, MMP억제제(MMPI III)를 따로 투여한 것과 두 약물을 동시에 투여한 것을 비교하였다. 또한 Doxorubicin의 작용이 Fas/FasL 경로를 통해 유발되는지 알아보기 위해 Fas 중화항체를 doxorubicin과 함께 투여하였다. 약물을 처리하여 배양한 세포에서 발생한 세포자멸사와 세포괴사를 확인하기 위해서 유세포 검사를 시행하였다. 결과: Doxorubicin을 처리한 세포가 처리하지 않은 세포보다 약물 농도에서 더 많은 세포괴사(p=0.000)를 보였다. 이에 반해 MMPI III를 처리한 세포는 약물 농도와 반응시간에 따른 세포자멸사 및 세포괴사에서 차이를 보이지 않았다. 두 약물을 동시에 투여한 군은 그렇지 않은 군에 비해 세포 자멸사 및 세포괴사에서 차이가 없었다. Doxorubicin에 Fas 중화항체를 추가한 군과 doxorubicin 단독 투여 군 사이에 세포자멸사 및 세포괴사에서 차이가 없었다. 결론: Doxorubicin과 같이 MMP 억제제를 골육종 치료에 사용하려면 wild-type p53 뿐만 아니라 wild-type p14를 가지고 있는 골육종 세포에 대한 검사가 필요할 것으로 사료된다.

• 대한한의학회지
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• 제23권2호
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• pp.190-197
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• 2002

Objectives : This study was performed to examine the effect of Yukmigiwhang-tang kamibang, a mixture of oriental herbal extracts, on the transcription of bone fonnation genes, BMP4 (bone morphogenetic protein 4) and TG2 (transglutaminase-2). Methods : Bone-related cells, MG-63 (human male osteosarcoma), HOS-TE85 (human female osteosarcoma), and KG-l (bone marrow) were cultured with portions of Yukmigiwhang-tang kamibang and the transcription activities of bone-related genes, BMP4 (bone morphogenetic protein 4) and TG2 (transglutaminase-2), were determined by Reverse-Transcription Polymerase Chain Reaction (RT-PCR). Results : Transcription of BMP4 gene in HOS-TE85 cell increased up to 40% at 0.3% (v/v) of Yukmigiwhang- tang kamibang extract and that of TG2 gene in MG-63 cells also increased up to 40% at 0.3-0.4% of the same extract. Although it was less significant when compared to those in other cells, the transcription of BMP4 gene in KG-l cells also increased up to 10 to 25%. Conclusions : These results clearly demonstrated that Yukmigiwhang-tang kamibang have an effect on transcription activity of bone-related genes, TG2 and BMP4, suggesting that it may play an important role in bone formation.

• The Korean Journal of Physiology and Pharmacology
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• 제10권3호
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• pp.143-147
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• 2006

Carthamus tinctorius L.is known to improve fracture healing, and bone morphogenetic proteins (BMPs) are associated with the formation and healing process of bone. BMP-2 and BMP-7 are two of the most important BMPs during the bone healing process. Human osteosarcoma MG63 cells and rats were used to determine the effects of Carthamus tinctorius L. extract (CTE) on BMP-2 gene expression. BMP-2 gene expression by CTE treatment in human osteosarcoma MG63 cells was not different from the control group until 8 hours of incubation, but was significantly higher, by 31%, than that of the control group at 16 hr of incubation. Microscopic findings of the 9th rib 3 weeks after fracture showed typical rimming of the osteoblast and immature bone formation in control and CTE groups. BMP-2 gene expression by in situ hybridization was remarkably increased by a CTE-supplemented diet in the fracture group compared to the control group. In conclusion, Carthamus tinctorius L. increased BMP-2 gene expression in human osteosarcoma cells and fractured bone. But further studies would be needed to elucidate the effect of CTE on fracture healing in vivo because our results did not show any evidence of healing improvement histologically $3^{rd}$ week after fracture.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제22권1호
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• pp.92-97
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• 2000

하악골에서 low grade 골육종은 매우 드물게 보고되고 있으며 조직검사상 conventional osteosarcoma와는 달리 pleomorphism을 보이지 않기 때문에 양성종양으로 underdiagnosis되기 쉽다. 그러나 정확한 환자의 진단은 적절한 치료와 환자의 예후에 영향을 큰 영향을 미친다. 그러므로 조기에 정확한 진단을 위하여는 의심되는 여러부위에서 조직검사를 시행하고 임상소견과 방사선소견 등을 병리의사와 공유하여야 한다. 이에 저자들은 초기에 진단이 어려웠던 하악골에 발생된 low grade 골육종을 경험하였기에 문헌고찰과 함께 보고하는 바이다.

• 대한골관절종양학회지
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• 제5권4호
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• pp.221-228
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• 1999

The purpose of this study was to verify the importance of apoptosis in genesis of osteosarcoma and whether apoptosis may play an important role as a predictive factor for the response to chemotherapy. Of the patients who were diagnosed osteosarcoma between January 1995 and June 1999, ten patients were selected. All specimens were obtained before and after preoperative chemotherapy and examined for the occurrence of apoptosis. Apoptosis was investigated by in situ end-labeling technique on paraffin-embedded sections and apoptotic indices were calculated before and after chemotherapy. The ages of ten patients ranged from 15 to 59 with equal sex ratio. All patients completed the planned pre-operative chemotherapy. Apoptosis occurs in osteosarcoma and apoptotic indices are increased after chemotherapy. Mean apoptotic index (AI) before and after chemotherapy were 17.2 (range 6-28.9) and 26.3 (9.6-46.2), respectively. Apoptotic cells were usually present around the necrotic area. The AI was increased as the progression of stage and in responder group more than in non-responder. Apoptosis is induced by pre-operative chemotherapy and the response is variable. Changes in AI levels before and after chemotherapy may possibly predict an individual patient's overall response.

• Biomolecules & Therapeutics
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• 제21권3호
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• pp.204-209
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• 2013

Osteoprotegerin (OPG) is a secreted glycoprotein and a member of the tumor necrosis factor receptor superfamily. It usually functions in bone remodeling, by inhibiting osteoclastogenesis through interaction with a receptor activator of the nuclear factor ${\kappa}B$ (RANKL). Transglutaminases-2 (Tgase-2) is a group of multifunctional enzymes that plays a role in cancer cell metastasis and bone formation. However, relationship between OPG and Tgase-2 is not studied. Therefore, we investigated the involvement of 12-O-Tetradecanoylphorbol 13-acetate in the expression of OPG in MG-63 osteosarcoma cells. Interleukin-$1{\beta}$ time-dependently induced OPG and Tgase-2 expression in cell lysates and media of the MG-63 cells by a Western blot. Additional 110 kda band was found in the media of MG-63 cells. 12-O-Tetradecanoylphorbol 13-acetate also induced OPG and Tgase-2 expression. However, an 110 kda band was not found in TPA-treated media of MG-63 cells. Cystamine, a Tgase-2 inhibitor, dose-dependently suppressed the expression of OPG in MG-63 cells. Gene silencing of Tgase-2 also significantly suppressed the expression of OPG in MG-63 cells. Next, we examined whether a band of 110 kda of OPG contains an isopeptide bond, an indication of Tgase-2 action, by monoclonal antibody specific for the isopeptide bond. However, we could not find the isopeptide bond at 110 kda but 77 kda, which is believed to be the band position of Tgase-2. This suggested that 110 kda is not the direct product of Tgase-2's action. All together, OPG and Tgase-2 is induced by IL-$1{\beta}$ or TPA in MG-63 cells and Tgase-2 is involved in OPG expression in MG-63 cells.

• Natural Product Sciences
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• 제13권1호
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• pp.1-5
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• 2007

Dietary flavonoids have antioxidant and antitumor promoting effects. Rhus verniciflua Stokes (RVS) is a flavonoid-rich herbal medicine and has long been used as a food additive and an antitumor agent in Korea. Previous study demonstrated that a purified flavonoid fraction prepared from RVS, herein named RCMF (the RVS chloroform-methanol fraction), exhibited growth inhibition and induced apoptosis in human osteosarcoma(HOS) cells. This study evaluated if p53-mediated pathway is associated with the RCMF-induced apoptosis in HOS cells. RCMF was shown to be capable of inducing apoptosis of the cells, as expected, and transparently increased p53 expression in the cells. However, the RCMF-induced cytotoxicity was suppressed by transfecting the cells with antisense p53 oligonucleotide, which also inhibited the decrease of Bcl-2 and the increase of Bax in mitochondria, and the release of cytochrome c into cytosol. This finding suggests that p53-mediated mitochondrial stress is required for RCMF-induced apoptosis in HOS cells.

• 대한수의학회지
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• 제57권1호
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• pp.59-61
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• 2017

A 15-year-old castrated mixed breed dog presented due to a 5-month history of cough and difficulty in ambulation. Necropsy showed multiple periosteal and intramedullary infiltrative masses in the appendicular skeleton. In addition, single and multiple neoplastic nodules were observed in several organs, including the lungs, liver, kidney, and heart. Microscopically, several skeletal neoplastic masses and nodules in the parenchymal organs revealed similar changes. The neoplastic cells were spindle- to polygonal-shaped with prominent osteoid production and occasional cartilaginous and bone formation. Based on the gross findings and histopathology results, the case was diagnosed as multicentric osteosarcoma with systemic metastases.

• BMB Reports
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• 제40권6호
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• pp.1069-1076
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• 2007

Cancer cells, characterized by local invasion and distant metastasis, are very much dependant on the extracellular matrix. The expression of matrix metalloproteinases (MMPs) has been implicated in the invasion and metastasis of cancer cells. In this study, we reported the effects of disulfiram, a clinically used anti-alcoholism drug, on tumor invasion suppression, as well as its effects on the activity of MMP-2 and MMP-9 in human osteosarcoma cells (U2OS). Disulfiram has been used for alcohol aversion therapy. However, recent reports have shown that disulfiram may have potential in the treatment of human cancers. Herewith, we showed that the anti-tumor effects of disulfiram, in an invasion assay using U2OS cells and that disulfiram has a type IV collagenase inhibitory activity that inhibits expression of genes and proteins responsible for both cell and non-cell mediated invasion on pathways. In conclusion, disulfiram inhibited expression of MMP-2 and MMP-9 and it regulated the invasion of human osteosarcoma cells. These observations raise the possibility of disulfiram being used clinical for the inhibition of cancer invasion.

• 대한골관절종양학회지
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• 제3권2호
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• pp.119-126
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• 1997

1980년부터 1997년까지 본 대학부속 성모병원에서 치료한 동측 대퇴골에 발생한 골육종 3예의 도약전이를 경험하였다. 도약전이는 골육종 환자 총 19례중 3례(15%)에서 발견되었고, 방사선 골주사나 자기공명영상이 진단에 필수적이었고, 고관절 이단술로 치료하였다. 도약전이의 기전은 확실하지 않았으나, 이시발생(metachronous) 기전의 초기단계로 보는것이 타당한 것으로 사료되었다. 증례 수가 적어 통계적 의미는 부여할 수 없으나, 도약전이가 있는 장관골의 골육종의 치료는 그 예후가 특히 불량하므로, 확실한 항암요법이 보장되지 않는 한 원발 종양이 발생한 장관골의 전체를 절제하거나 병소 상부관절에서 이단술을 시행하는 것이 바람직하다고 판단되었다.