• 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.

• Korean Journal of Clinical Pharmacy
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• v.16 no.1
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• pp.1-8
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• 2006

Methotrexate(MTX)는 소아 골육종 환자에서 $12g/m^2$의 고용량을 사용하고 있다. 현재, 소아 골육종 환자에서 신기 능에 따른 고용량 MTX의 임상 약동학은 연구되어 있지 않다. 따라서 본 연구에서는 신기능에 따른 MTX 약동학을 이용하여 구내염을 최소화하는 방법을 제시하고자 하였다. 방법: 환자들의 의무기록지를 후향적 방법으로 검토하였다. 한 병원에서 골육종으로 진단받고, 치료 받은 환자들을 대상으로 정상 신기능군과 비정상 신기능군으로 나누었다. 두 군에 MTX 투여 후 혈중 농도를 각각 비교하였고, 최고 혈중농도도 비교하였다. 혈중 농도와 구내염의 관련성, CL, AUC와 구내염의 상관관계를 분석하였다. 각 군의 terminal half-life, CL, Vss의 평균과 mea residence time(MRT)의 평균을 구하였고, 두 군간 각각을 비교하였다 $({\alpha}=0.05)$. 결과: 환자는 6명이었고, 평가 가능한 총 MTX 투여 회수는 34회였다. MTX 투여 후 최고혈중 농도, 24,48 시간의 혈중농도는 통계적으로 유의성 있는 차이가 있었고, 72,96 시간에서의 농도는 두 군간 유의성이 없었다. 각 군에서 혈중농도와 구내염의 상관관계, 그리고 CL, AUC와 구내염의 상관관계는 발견되지 않았다. Vss를 제외한 모든 파라미터들(terminal half-life, CL, MRT)은 통계적으로 유의성 있는 차이가 있었다. 결론: 비정상 신기능 군에서 MTX 투여 시작 후 24, 48 시간에서의 혈중농도가 더 높고, 변동이 심했다. 또한 MTX의 CL는 감소했고, 혈중농도는 증가하였다. 이러한 사실로 MTX 투여 전 후 혈중 크레아티닌이나 또는 크레아티닌 청소율 모니터링이 필요하다는 것을 알 수 있으며, MTX 투여가 끝난 직후 그리고 그 이후 24 시간 간격으로 혈중 농도를 측정해야함을 알 수 있다.

• The Journal of the Korean bone and joint tumor society
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• v.18 no.1
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• pp.14-19
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• 2012

Purpose: We analyzed the oncologic outcome of the malignant transformed benign giant cell tumor of bone. Materials and Methods: Between January 2000 and February 2012, 5 cases were referred with suspicious malignant transformation of benign giant cell tumor. No patients underwent radiation therapy. Results: After referral, all patients received the wide excision of the tumor and its' pathologic diagnosis were osteosarcoma. As classified by the location of tumor lesion, 3 cases were located in the distal femur, 1 case was in the distal radius and 1 case was in the proximal femur. The average latent period between diagnosis of benign giant cell tumor and diagnosis of secondary malignant giant cell tumor was 49.2 months. (range, 24-126 months) The mean follow-up period was 21.6 months. There were subsequent local recurrence in 2 cases and 3 patients developed distant metastasis. All patients with lung metastasis were dead. Conclusion: Malignant transformation of benign giant cell tumor of bone can be occurred within 5 years. Therefore, when benign giant cell tumor suspicious malignant transformation, it is necessary to do more aggressive treatment.

• The Journal of the Korean bone and joint tumor society
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• v.11 no.2
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• pp.118-125
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• 2005

Purpose: The expression of apoptosis-related genes, such as survivin, bcl-2, and bax has been examined in the human osteosarcoma and then evaluated the correlation with clinical data of patients. Materials and Methods: Fifty human osteosarcoma specimens were established from incisional biopsy and examination of survivin, bcl-2, and bax by immunohistochemical study was performed. We investigated the correlation of survivin, bcl-2, bax and their two or three combined expressions with clinical data including the response of chemotherapy, local recurrence, distance metastasis, and oncologic outcome. Results: Survivin was showed in 26 cases (52%), bcl-2 in 23 cases (46%), and bax in 21 cases (42%) osteosarcoma. And coexpression of survivin and bcl-2 was showed in 19 cases (38%), survivin and bax in 13 cases (26%), bcl-2 and bax in 8 cases (16%), and all three expression was showed in 8 cases (16%). There was no correlation between their apoptosis related gene and histologic difference, the presence of local recurrence and distant metastasis. Whereas neoadjuvant chemotherapy response correlated with bcl-2 expression (P=0.04), and survivin and bcl-2 coexpression (P=0.044) with poor chemoresponse. The rate of died of disease was correlated with bcl-2 (P=0.001), survivin and bcl-2 coexpression (P=0.027) with bad outcome. Survival curves of bcl-2 (P=0.0075), survivin and bcl-2 (P=0.0012) was showed negative correlation in the Kaplan-Meier method. Conclusion: The apoptosis related gene expression was relatively high in osteosarcoma, bcl-2 expression was correlated with poor chemotherapy response and poor survival rate, but survivin was correlated with this oncologic outcome only in the bcl-2 coexpression. The examination of immunohistochemical stain of apoptosis related gene in osteosarcoma could be helpful in the judgment of osteosarcoma prognosis.

• 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.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 the Korean bone and joint tumor society
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• v.20 no.2
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• pp.66-73
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• 2014

Purpose: Various diagnostic imaging modalities have been used to evaluate the effect of neoadjuvant chemotherapy for osteosarcoma early and noninvasively. We evaluated the effectiveness of imaging studies of plain radiographs and positron-emission tomography/computed tomography (PET/CT) in predicting neoadjuvant chemotherapy effect for osteosarcoma and tried to establish a general principle in interpretation of PET/CT parameters. Materials and Methods: Eighteen patients who underwent two cycles of neoadjuvant chemotherapy and surgical excision for osteosarcoma were enrolled. There were 13 males and 5 females, with a median age of 19 (11-63) years. Fifteen patients of 18 had the American Joint Committe on Cancer (AJCC) stage IIB. They had plain radiographs and PET/CT before and after neoadjuvant chemotherapy. The resected tumor specimens were pathologically examined to determine histological response grade using a conventional mapping method. Statistical analysis was performed to evaluate the correlation between histopathological necrosis rate, and radiographic finding category, post-chemotherapy maximum standardized uptake value (SUVmax), average standardized uptake value and metabolic tumor volume (MTV) as well as reduction rates of them. Results: Eight patients were good responders to neoadjuvant chemotherapy based on histological evaluation. Median SUVmax reduction rate was 73 (23-77) % in good responders and 42 (-32-76) % in poor responders. Median MTV reduction rate was 93.5 (62-99) % in good responders and 46 (-81-100) % in poor responders. While radiographic finding category was not different according to histological response (p=1.0), SUVmax reduction rate was significantly different (p=0.041). Difference in MTV reduction rates approached statistical significance as well (p=0.071). Conclusion: While radiographic finding category was not reliable to assess neoadjuvant chemotherapy effect for osteosarcoma, reduction rate of SUVmax was a useful indicator in this study. As parameters of PET/CT can be influenced by various factors of settings, different centers have to make an effort to establish their own standard of judgement with reference of previous studies.

• Journal of Chest Surgery
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• v.40 no.9
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• pp.607-612
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• 2007

Background: Surgical resection is a standard treatment for pulmonary metastases in patients with osteosarcoma, but the role of performing repeated resections is not clear. This study was designed to clarify the feasibility of performing a repeated pulmonary metastasectomy and the prognostic factors for pulmonary metastases in patients with osteosarcoma. Material and Method: Between January 1990 and July 2005, 62 patients with osteosarcoma were diagnosed with pulmonary metastases and 36 patients underwent pulmonary resection. We reviewed the patients retrospectively. Result: The total number of pulmonary metastasectomies was 62 in 30 patients. Among 36 patients, 18 had a second metastasectomy, 7 had a third metastasectomy, and one patient had a fourth metastasectomy. There was no distinctive difference between the first and second metastatectomy in terms of median survival time, and the 3-year and 5-year survival rate (first resection: 20.5 months, 32.0% and 29,4%; second resection: 11.3 months, 34.9% and 34.%). However, the median survival time (7.1 months) was shorter in patients with a third metastatectomy than in patients with one metastatectomy (p=0.01). In long-term survivors, the number of female patients, patients with a disease free time longer than 12 months, patients with a single metastasis and patients with anatomic resection was larger when compared to non-long term survivors, but showed no statistical significance. Conclusion: Repeated pulmonary metastasectomy is expected to prolong survival time in patients with osteosarcoma, and is expected to increase long-term survival in selected cases. Further studies with a large number of patients are necessary.

• The Journal of the Korean bone and joint tumor society
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• v.14 no.2
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• pp.140-145
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• 2008

After limb salvage operation becomes popular, reconstruction method of epi-metaphyseal osteosarcoma is relatively standardized though it may be operator's matter of preference. Most limb salvage techniques presently used are prosthesis reconstruction and osteoarticular allograft. In the case of prosthesis, it is very stable and shows good postoperative functional score, however, finally, it has a weak point of requirement for removal procedure due to failure. In the long run, allograft reconstruction has a good merit. But, it has a weak point of difficulties in securing the demanded size and shape. Allograft reconstruction should be performed only in the case of safe margin and established indication. In limb salvage operation, intercalary reconstruction is useful method in diaphyseal osteosarcoma, however, in metaphyseal osteosarcoma, the indication is not confirmed. We treated 17 year old osteosarcoma patient with localized in the tibial medial condyle with proximal medial condylectomy and pasteurized bone reconstruction in the conviction of safe surgical margin. We report this case because we guess if this procedure may be applied to premature patients, despite failure hemiarthroplasty can be tried successfully.

• Journal of Veterinary Clinics
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• v.27 no.5
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• pp.588-592
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• 2010

A 15-year-old neutered male Yorkshire terrier was presented with a gait disorder of the pelvic limbs. For differential diagnosis of neural disease, magnetic resonance imaging (MRI) and computed tomography (CT) scan were performed. CT showed bone defect in the 4th lumbar vertebra and adjacent soft tissue mass. MRI revealed a mass in left side of the 4th lumbar vertebra. The mass was uniformly enhanced on contrast-enhanced T1-weighted imaging (T1W1). Excision of the mass alleviated back pain. Vertebral osteosarcoma was identified by the histopathological examination. Therefore, CT and MRI were helpful to diagnose vertebral osteosarcoma in the dog and to plan surgical excision of the mass.