• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.5967-5976
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• 2014

Treating the osteosarcoma (OSA) remains a challenge. Current strategies focus on the primary tumor and have limited efficacy for metastatic OSA. A better understanding of the OSA pathogenesis may provide a rational basis for innovative treatment strategies especially for metastases. The aim of this review is to give an overview of the molecular mechanisms of OSA tumorigenesis, OSA cell proliferation, apoptosis, migration, and chemotherapy resistance, and how improved understanding might contribute to designing a better treatment target for OSA.

• The Journal of the Korean bone and joint tumor society
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• v.18 no.2
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• pp.59-65
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• 2012

Purpose: Multidisciplinary approaches of surgical resection and chemotherapy have been widely used for the treatment of non-metastatic osteosarcomas. We aimed to assess the effect of neoadjuvant chemotherapy for metastasis and disease-specific survival. Materials and Methods: Authors retrospectively reviewed 225 young (<30 years old) and non-metastatic osteosarcoma patients who underwent surgical resection and postoperative chemotherapy between February 1984 and July 2010. Mean age was 14.4 years old (ranged: 4-29 years old) and average follow-up period was 9.1 years (2-28 years). The patients were divided into two groups according to the application of preoperative chemotherapy. Both groups were compared with clinical characteristics, metastasis-free survival and disease-specific survival. Results: All of 225 patients, 32 patients were treated with postoperative chemotherapy and 193 patients were performed preoperative and postoperative chemotherapy. Postoperative chemotherapy group showed significantly high rate of amputation (p<0.001). Metastasis was occurred in 101 patients. Postoperative chemotherapy group indicated significant higher rate of metastasis (69% vs 41%, p=0.004) and early development of metastasis (mean: 11.5 vs 20.3 months, p=0.045) than pre-and postoperative chemotherapy group. Fifty-seven patients were died of osteosarcoma. Postoperative chemotherapy group revealed significant lower rate of 5-year disease-specific survival than pre-and postoperative chemotherapy group (51% vs 84%, p=0.001). Adult (>15 years) and large sized tumor (>8 cm) were meaningful risk factors of metastasis and disease-specific survival. Although, local recurrences were occurred in 13 patients, there was no significant difference. Conclusion: Neoadjuvant chemotherapy offers better disease-specific survival and metastasis-free survival.

• Journal of Chest Surgery
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• v.25 no.10
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• pp.1030-1034
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• 1992

There are follow-up data according to thirteen patients recieved the surgical resection for metastatic lung cancer arising from different primary tumor. The patients were received the surgical resection at Korean Cancer Center Hospital from July 1987 to Setember 1991 and followed-up to August 1992. There were 9 men and 4 women, ranging in age from 16 to 70 years[mean age, 42.8 years]. The primary tumors were 2 synovial sarcoma, 2 sarcoma, 2 osteosarcoma, 3 laryngeal ca, 1 melanoma, 1 ovarian ca and 1 bladder ca. The operative procedures were 5 wedge resections, 1 segmental resection, 5 lobectomies, 1 bil-obectomy and 1 pneumonectomy. There was no operative and hospital death. There were 3 deaths[each survival period: 2, 9 and 20 months, average 10.3 months]and 5 tumor recurrence during follow-up. At now, the average survival period of aliving patients is 29.1 months.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9823-9829
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• 2014

Background: High-dose methotrexate (HD-MTX) is recognized as an efficient component of therapy against pediatric osteosarcoma in combination with other drugs such as cisplatin (CDP), carboplatin (CBDCA), doxorubicin (ADM), etoposide (VP-16) and ifosfamide (IFO). Objectives: To demonstrate the feasibility and effectiveness of the HD-MTX/CDP/DOX/VP-16/IFO [MTX(+)] protocol comparable to CDP/ADM/CBDCA/IFO [MTX(-)] for treating childhood osteosarcoma at Ramathibodi Hospital (1999-2014). Materials and Methods: A retrospective analysis was conducted of osteosarcoma patients aged less than 18 years treated with two chemotherapeutic regimens between 1999 and 2014. A total of 45 patients received the MTX(-) and 21 the MTX(+) protocol. Results: Overall limb-salvage and amputation rate were 12.9% and 77.7%, respectively. Kaplan-Meier analysis results for 3-year disease free survival (DFS) and overall survival (OS) regardless of treatment regimens were $43.4{\pm}6.0%$ and $53.2{\pm}6.1%$ respectively. The 3-year DFS and OS were improved significantly with the MTX(+) protocol compared to MTX(-) protocol (p=0.010 and p=0.009, log rank test) [$69.8{\pm}10.5%$, $79.8{\pm}9.1%$ for MTX(+) and $31.1{\pm}6.9%$, $42.2{\pm}7.4%$ for MTX(-) protocol, respectively]. Patients with metastatic osteosarcoma treated with the MTX(+) protocol had statistically significant higher 3-year DFS and OS than those treated with the MTX(-) protocol ($66.7{\pm}13.6%$ and $15.0{\pm}8.0%$ for 3-year DFS, p=0.010, $73.3{\pm}13.2%$ and $20{\pm}8.9%$ for 3-year OS, p=0.006, respectively). The independent risk factors for having inferior 3-year DFS and OS were poor histological response (tumor necrosis <90%) and treatment with the MTX(-) protocol. The multivariate analysis identified only the treatment with the MTX(-) protocol as an independent predictor of inferior OS with a hazard ratio (HR) of 3.53 (95% confidence interval of 1.2-10.41, p=0.022). Conclusions: Our study demonstrated the tolerability, feasibility and efficacy of the HDMTX-based regimen improving the survival rate in pediatric osteosarcoma cases, in line with reports from developed countries.

• The Journal of the Korean bone and joint tumor society
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• v.13 no.2
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• pp.195-200
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• 2007

Dedifferentiated parosteal osteosarcoma is an uncommon variant of osteosarcoma. Dedifferentiation is known to be associated with a greater metastatic potential and a more rapid lethal clinical course. Thus recognition of dedifferentiation is important to establish the treatment strategy. But there may be few significant clinical clues to distinguish between dedifferentiated parosteal osteosarcoma and conventional one. A 29-year-old woman presented with 2-year history of discomfort and swelling in her proximal thigh. Examination showed a large, hard, non-mobile mass. Radiographs revealed a large ossified mass attached to the proximal femur. Diagnosis of parosteal osteosarcoma was established by MRI and needle biopsy. But she had a history of abrupt severe thigh pain and increased swelling before surgery. Follow up MRI showed enlargement of mass with invasion to muscle around tumor. The patient underwent an en-bloc resection of tumor and reconstruction. Histological examination showed parosteal sarcoma with dedifferentiation. The patient expired due to local recurrence of tumor and distant lung metastasis 2 months after the surgery. In case with rapid growth of a lesion or unusual severe pain, one must have a high index of suspicion with regard to dedifferentiation.

• Journal of Chest Surgery
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• v.13 no.4
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• pp.486-489
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• 1980

16 cases of the chest wall tumors that had been treated at the dept. of thoracic & cardiovascular surgery, Chungnam National University Hospital, for 3.5 years from Jan. 1977 to Jun. 1980 were analyzed. The results were as follows; 1. Generally the chest wall tumors were most frequent in the thirties, the youngest age was 2 years, and the oldest 65 years. The incidence rate of male to female was 1.3:1. The malignant tumors were common in the fifties & sixties, the incidence rate of male to female 5:1. 2. The common disease entities were rib tuberculosis [43.7%] and metastatic tumor [25.0%], and the another chondrosarcoma, osteosarcoma, fibrous dysplasia, chronic osteomyelitis, and granuloma accompanying with acute osteomyelitis by Klebsiella infection were 6.3%, respectively. 3. The common manifestations were local swelling [100.0%] and local chest pain [43.8%].

• Molecules and Cells
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• v.41 no.6
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• pp.523-531
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• 2018

Tumour metastasis is one of the most serious challenges of cancer as it is the major cause of mortality in patients with solid tumours, including osteosarcoma (OS). In this regard, anti-metastatic genes have potential for metastasis inhibition strategies. Recent evidence showed the importance of breast cancer metastasis suppressor 1 (BRMS1) in control of OS invasiveness, but the regulation of BRMS1 in OS remains largely unknown. Here, we used bioinformatics analyses to predict BRMS1-targeting microRNAs (miRNAs), and the functional binding of miRNAs to BRMS1 mRNA was evaluated using a dual luciferase reporter assay. Among all BRMS1-targeting miRNAs, only miR-151b, miR-7-5p and miR-3200-5p showed significant expression in OS specimens. Specifically, we found that only miR-3200-5p significantly inhibited protein translation of BRMS1 via pairing to the 3'-UTR of the BRMS1 mRNA. Moreover, we detected significantly lower BRMS1 and significantly higher miR-3200-5p in the OS specimens compared to the paired adjacent non-tumour bone tissues. Furthermore, BRMS1 and miR-3200-5p levels were inversely correlated to each other. Low BRMS1 was correlated with metastasis and poor patient survival. In vitro, overexpression of miR-3200-5p significantly decreased BRMS1 levels and promoted OS cell invasion and migration, while depletion of miR-3200-5p significantly increased BRMS1 levels and inhibited OS cell invasion and migration. Thus, our study revealed that miR-3200-5p may be a critical regulator of OS cell invasiveness.

• Molecules and Cells
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• v.22 no.3
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• pp.291-299
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• 2006

Vitexin, a natural flavonoid compound identified as apigenin-8-C-${\beta}$-D-glucopyranoside, has been reported to exhibit antioxidative and anti-inflammatory properties. In this study, we investigated its effect on hypoxiainducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) in rat pheochromacytoma (PC12), human osteosarcoma (HOS) and human hepatoma (HepG2) cells. Vitexin inhibited HIF-$1{\alpha}$ in PC12 cells, but not in HOS or HepG2 cells. In addition, it diminished the mRNA levels of hypoxia-inducible genes such as vascular endothelial growth factor (VEGF), smad3, aldolase A, enolase 1, and collagen type III in the PC12 cells. We found that vitexin inhibited the migration of PC12 cells as well as their invasion rates, and it also inhibited tube formation by human umbilical vein endothelium cells (HUVECs). Interestingly, vitexin inhibited the hypoxia-induced activation of c-jun N-terminal kinase (JNK), but not of extracellular-signal regulated protein kinase (ERK), implying that it acts in part via the JNK pathway. Overall, these results suggest the potential use of vitexin as a treatment for diseases such as cancer.

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.285-293
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• 2002

Background : The lung is the most common site for a metastasis of extrapulmonary malignant tumors. however, reports on an endobronchial metastasis are rare. An endobronchial metastasis is defined as a documented extrapulmonary neoplasms metastatic to the segmental or more proximal central bronchus within a bronchoscopically visible range. The purpose of this study was to define the clinical characteristics of an endobronchial metastasis of extrapulmonary malignancies. Materials and Methods : The clinical features and treatment outcomes of 27 endobronchial metastatic cancer cases were reviewed from June, 1991 to May, 2001 in the Severance Hospital. Results : The patients' age ranged from 18 to 75. There were 17 men and 10 women. The primary tumors included the colorectum in 7, the uterine cervix in 4, the stomach and the breast in 3 patients each, and an osteosarcoma in 2 patients. The main complaint of most patients was coughing and a chest X-ray revealed a hilar mass, a parenchymal, and an atelectasis. The mean recurrence interval time was 45.5 months. The median and mean survival times were 10 and 12.3 months, respectively. Conclusion : An endobronchial metastasis is an ominous finding, and is associated with advanced-stage diseases. It requires differential diagnosis with a primary bronchogenic carcinoma. If atypical clinical features are present or an atypical cell type is discovered by a biopsy of the lesion in the lung mass, the appropriate diagnostic studies should be undertaken.

• Journal of Yeungnam Medical Science
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• v.20 no.2
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• pp.187-196
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• 2003

The cytokines are the hormone-like proteins, which are produced in the mononuclear cells. They have many roles, such as immune mediators, cell differentiations, angiogenesis. The chemokines have chemotactic effects which control the host immune response. There were few reports about the cytokines associated with musculoskeletal tumors. From late 1980s, the cytokine studies of bone tumors such as osteosarcoma were started, but most studies for benign and malignant musculoskeletal tumors were left to be explored. To evaluate the characteristics of the cytokines in variable musculoskeletal tumors, tissues were obtained from the seven patients who visited the Yeungnam University hospital from February to July 2000. They were lipoma (1 case), parosteal osteoma (1 case), enchondroma (2 cases), pigmented villonodular synovitis (1 case), ganglion (1 case), and metastaic squamous cell carcinoma (1 case). The gene experession of the cytokines were analyzed by RNase protection assay (RPA) and reverse transcription-polymerase chain reaction (RT-PCR). The lipoma and parosteal osteoma expressed MIP-$1{\beta}$, and IP-10 genes. The two enchondromas showed different results, one expressed all of MIP-$1{\alpha}$, MIP-$1{\beta}$ and IP-10 genes but the other expressed none of above. The pigmented villonodular synovitis strongly expressed MIP-$1{\alpha}$ and IP-10 when compared with the other cases. The ganglion did not express all of the chemokines mentioned above. And the metastatic squamous cell carcinoma expressed all of the chemokines and especially IP-10 was highly expressed. Even though this study has only a few cases, these results provide a basis for the cytokine mediating network study in musculoskeletal tumors.