• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3821-3824
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• 2012

Aim: SNPs of ERCC1 and ERCC2 genes have been found to be associated with response to platinum therapy in different clinical settings. In the current study, we investigated the relationship of SNPs in ERCC1 and ERCC2 to cisplain response and survival in osteosarcoma patients. Methods: 267 consecutive patients diagnosed with osteosarcoma between January 2003 to January 2005 were followed up until the end of January 2010. ERCC1 Asn118Asn, ERCC1 Gln504Lys, ERCC2 Asp312Asn and ERCC2 Lys751Gln polymorphisms were detected based upon the Sequenom MassARRAY platform.Results: For ERCC1 Asn118Asn, the variant genotype T/T was strongly significantly associated with a higher event free survival when compared with the wild-type C/C, with an adjusted OR (95% CI) of 0.39 (0.14-0.95). ERCC2 751 A/A genotype showed increased event free survival of osteosarcoma (HR=0.44; 95%CI=0.10-0.87). However, we did not find significant association of ERCC1 Gln504Lys and ERCC2 Asp312Asn polymorphisms with prognosis of osteosarcoma. Conclusions: We first report associations of four SNPs, ERCC1 Asn118Asn, ERCC1 Gln504Lys, ERCC2 Asp312Asn and ERCC2 Lys751Gln, with risk of death from osteosarcoma in a Chinese population, indicating ERCC1 118T/T and ERCC2 A/A may be used as surrogate markers for clinical outcome of osteosarcoma treatmetn with cisplain.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3103-3107
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• 2012

Osteosarcoma, the most common primary mesenchymal malignant tumor, usually has bad prognosis in man, with cancer stem-like cells (CSCs) considered to play a critical role in tumorigenesis and drug-resistance. It is known that phosphatidylinositol 3-kinase (PI3K) is involved in regulation of tumor cell fates, such as proliferation, cell cycling, survival and apoptosis. Whether and how PI3K and inhibitors might cooperate in human osteosarcoma CSCs is still unknown. We therefore evaluated the effects of LY294002, a PI3K inhibitor, on the cell cycle and apoptosis of osteosarcoma CSCs in vitro. LY294002 prevented phosphorylation of protein kinase B (PKB/Akt) by inhibition of PI3K phosphorylation activity, thereby inducing G0/G1 cell cycle arrest and apoptosis in osteosarcoma CSCs. Further studies also demonstrated that apoptosis induction by LY294002 is accompanied by activation of caspase-9, caspase-3 and PARP, which are involved in the mitochondrial apoptosis pathway. Therefore, our results indicate PI3K inhibitors may represent a potential strategy for managing human osteosarcoma via affecting CSCs.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3455-3458
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• 2016

Osteosarcoma is a common primary malignant bone tumor in children and adolescents. Recent worldwide average incidences of osteosarcoma in people aged 0 to 24 years were 4.3 and 3.4 per million, respectively, with a ratio of 1.4:1. However, data on the incidence of osteosarcoma in Thailand are limited. This study analyzed the incidence of osteosarcoma in the upper northern region of Thailand, with a population of 5.85 million people (8.9% of the total Thai population), using data for the years 1998 to 2012, obtained from the Chiang Mai Cancer Registry (CMCR) at Chiang Mai University Hospital and the Lampang Cancer Registry (LCR) at the Lampang Cancer Hospital, a total of 144 cases. The overall annual incidence of osteosarcoma was 1.67 per million with a male:female ratio of 1.36:1. Incidences by age group (male and female) at 0 to 24, 25 to 59 and over 60 years were 3.5 (3.9 and 3.0), 0.8 (0.9 and 0.6), and 0.7 (0.8 and 0.5), respectively. The peak incidence occurred at 15 to 19 years for males and at 10 to 14 years for females. The median survival time was 18 months with a 5-year survival rate of 43%. Neither the age group nor the 5-year interval period of treatment was significantly correlated with survival during the 15-year period studied.

• Clinical and Experimental Pediatrics
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• v.59 no.9
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• pp.374-380
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• 2016

Purpose: Patients with unresectable, relapsed, or refractory osteosarcoma need a novel therapeutic agent. Metformin is a biguanide derivative used in the treatment of type II diabetes, and is recently gaining attention in cancer research. Methods: We evaluated the effect of metformin against human osteosarcoma. Four osteosarcoma cell lines (KHOS/NP, HOS, MG-63, U-2 OS) were treated with metformin and cell proliferation was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle progression and apoptosis were evaluated using flow cytometric analysis, and migration and wound healing assay were performed. Fourteen female Balb/c-nude mice received KHOS/NP cell grafts in their thigh, and were allowed access to metformin containing water (2 mg/mL) ad libitum. Tumor volume was measured every 3-4 days for a period of 4 weeks. Results: Metformin had a significant antiproliferative effect on human osteosarcoma cells. In particular, metformin inhibited the proliferation and migration of KHOS/NP cells by activation of AMP-activated protein kinase and consequent inhibition of the mammalian target of rapamycin pathway. It also inhibited the proliferation of cisplatin-resistant KHOS/NP clone cells. Analysis of KHOS/NP xenograft Balb/c-nude models indicated that metformin displayed potent in vivo antitumor effects. Conclusion: Further studies are necessary to explore metformin's therapeutic potential and the possibilities for its use as an adjuvant agent for osteosarcoma.

• The Journal of the Korean bone and joint tumor society
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• v.4 no.1
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• pp.65-70
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• 1998

Osteosarcoma is the most common primary bone tumor except for multiple myeloma. Hematogenous spread of osteosarcoma presents the t1susal route of dissemination. Lung metastasis is the most common, however the lymph node involvement is quite rare. In addition, according to Mirra, radiologically detectable involvement of lymph node is an extremely rare manifestation of osteosarcoma. The authors had experienced a patient with an osteosarcoma of the right distal femur which spread to the right inguinal lymph node and lung. After preoperative chemotheraphy, a limb salvage operation was performed around the lesion of right distal femur and the right inguinal lymph nodes were dissected. A adjuvant postoperative chemotheraphy was performed. After the treatment, there was no recurrence of osteosarcoma or any other metastatic evidence for two years and 8 months.

• The Journal of the Korean bone and joint tumor society
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• v.15 no.2
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• pp.104-110
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• 2009

Purpose: Compared to soft tissue sarcoma, the relative risk of extraskeletal osteosarcoma is still not clear. The purpose of this study is to identify the difference in survival and local recurrence rate between two soft tissue sarcomas. Materials and Methods: Twelve patients with pathologically confirmed extraskeletal osteosarcoma were analysed. For retrospective matched case-control study, we selected 72 patients who were confirmed as high grade soft tissue sarcoma and had similar tumor location, tumor size and age to extraskeletal osteosarcoma. Results: Median age was 50 years old. Five cases were located in upper extremity, four in the buttocks, three in the lower extremity. Overall survival rate of extraskeletal osteosarcoma group and high grade soft tissue sarcoma group at 5 years were 52% and 55%. There is no significant difference (p=0.8). Local recurrence rate and metastasis rate were 58%, 67% in extraskeletal osteosarcoma group and 36%, 51% in soft tissue sarcoma group, which were not stastistically significant(p=0.2, p=0.4). Conclusion: Extraskeletal osteosarcoma have similar local recurrence, metastasis and survival rate compare to high grade soft tissue sarcoma. The number of patients of this study were too small to identify outcome of extraskeletal osteosarcoma. Further multi-institutional study should be attempted.

• The Journal of the Korean bone and joint tumor society
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• v.11 no.1
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• pp.100-104
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• 2005

Osteosarcoma is the most common tumor in malignant bone tumors. The peak age incidence in osteosarcoma is between 10 to 14 years of age. This tumor rarely develops under 6 years of age and the youngest patient in the previous literature was a 13 months old girl who had an osteosarcoma involving the second metacarpal bone. We report a case of an 8 month old male infant, who had an osteosarcoma involving the right proximal tibia. This patient was treated by wide excision with transepiphyseal resection and reconstruction with allograft. At 20 months after operation, the varus deformity was developed at the proximal junctional site of allograft. Thereafter, the revision was performed with correction of deformity and augmentation with the proximal fibula transfer. At 51 months after operation, he has been remained as free of disease, and he has recovered the knee motion ranged from 15 degree to 75 degree. The osteosarcoma in infant is very rare but it should be considered the osteosarcoma in the differential diagnosis of any bone lesion. Instead of amputation, the limb sparing operation and the solutions for limb length inequility in growing period should be carefully considered in the infantile osteosarcoma.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5883-5886
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• 2012

Osteosarcoma is the most common primary bone malignancy in children and adolescents, and its clinical outcome is poor. We evaluated the response of GSTP1, ERCC1 and ERCC2 to chemotherapy among osteosarcoma patients, and the role of these genes on the prognosis of osteosarcoma. 187 patients with osteosarcoma were administered with methotrexate, cisplatin/adriamycin, actinomycin D, cyclophosphamide, or vincristine treatment. GSTP1, ERCC1 and ERCC2 polymorphism was genotyped by PCR-RFLP assay. The results showed the average survival time of 187 patients were 38.4 months. 97 patients showed response to neoadjuvant chemotherapy. The GSTP1 Val and ERCC2 A/A genotypes had significantly higher rates of response to chemotherapy, with adjusted OR (95% CI) of 2.19 (1.15-6.21) and 2.88 (1.14-13.25). Individuals with ERCC2 A/A genotype were likely to have a lower risk of death from oseosarcoma, and the adjusted HR was 0.32 (0.13-0.95). Our study indicated test of GSTP1 and ERCC2 Lys751Gln polymorphisms might be a candidate pharmacogenomic factors to be explored in the future to identify the osteosarcoma patients who might benefit from chemotherapy.

• Journal of Veterinary Clinics
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• v.25 no.3
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• pp.182-186
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• 2008

An 11-year-old mixed breed male dog was presented with a thoracoabdominal wall mass of 3-year duration. Initial tentative diagnosis of osteosarcoma was made. Despite chemotherapy treatment, 72 days following the date of presentation, the dog was euthanized. Based upon necropsy and histopathologic findings, the tumor was definitely diagnosed as a combined type osteosarcoma of the rib. At necropsy examination, the tumor extended the left kidney and diaphragm, but distant metastasis was not found. The tumor's weight was 2.3kg and that was 38.3% of the dog's weight. This case report describes the clinicopathological, computed tomographic, histopathologic and immunohistochemical findings of extensive rib osteosarcoma in a small breed dog.

• Journal of Korean Neurosurgical Society
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• v.29 no.5
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• pp.680-683
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• 2000

Osteosarcoma is the most frequently encountered primary malignant tumor of the bone. But primary osteosarcoma of the skull(POS) is rare. The author presents a case of skull neoplasm identified as osteogenic sarcoma. A twentyseven-years-old male patient was admitted because of painful swelling at left temporal and zygomatic area with impairment of extraocular movement. Chest film and long bone series showed no evidence of abnormality. Skull films revealed round irregular bony destructive area at the left pterional area. CT and MRI revealed expansile destruction of the left sphenoid bone, lateral orbital wall and temporal bone within the hemorrhagic mass lesions which showed wall enhancement. Histologic examination confirmed a rare variant of osteosarcoma of the telangiectatic type.