Osteosarcoma in Asian Populations Over the Age of 40 Years: A Multicenter Study

Joo, Min Wook; Shin, Seung Han; Kang, Yong Koo; Kawai, Akira; Kim, Han‐Soo; Asavamongkolkul, Apichat; Jeon, Dae‐Geun; Kim, Jae Do; Niu, Xiaohui; Tsuchiya, Hiroyuki; Puri, Ajay; Wang, Edward H. M.; Chung, So Hak; Chung, Yang Guk

doi:10.1245/s10434-015-4414-6

Cited by 36 publications

(38 citation statements)

References 22 publications

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“…Thirty‐five studies met the inclusion criteria (Table ): very high HDI (n = 23), high HDI (n = 7), and medium/low HDI (n = 5) . Figure depicts the prevalence of metastatic OS at diagnosis stratified by HDI group.…”

Section: Resultsmentioning

confidence: 99%

“…Thirty-five studies met the inclusion criteria (Table I): very high HDI (n = 23), [1,6,8,10,[13][14][15][16][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] high HDI (n = 7), [3,11,12,[36][37][38][39] and medium/low HDI (n = 5). [2,[40][41][42][43] Figure 1 depicts the prevalence of metastatic OS at diagnosis stratified by HDI group.…”

Section: Resultsmentioning

confidence: 99%

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Prevalence of Metastasis at Diagnosis of Osteosarcoma: An International Comparison

Marko

Diessner

Spector

2016

Pediatric Blood & Cancer

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Background Osteosarcoma is the most common primary malignant bone tumor in many countries, with metastatic disease responsible for most patient deaths. This study compares the prevalence of metastatic osteosarcoma at diagnosis across countries to inform the critical question of whether diagnostic delay or tumor biology drives metastases development prior to diagnosis. Procedure A literature search of the PubMed database was conducted to compare the prevalence of metastatic disease at the time of OS diagnosis between countries. A pooled prevalence with 95% confidence intervals was calculated for each study meeting inclusion criteria. Studies were grouped for analysis based on human development index (HDI) scores. Results Our analysis found an 18% (95% CI: 15%, 20%) average global pooled proportion of metastasis at osteosarcoma diagnosis. The average prevalence of metastasis at diagnosis increased as HDI groupings decreased, with very high HDI, high HDI, and medium/ low HDI groups found to be 15% (95% CI: 13%, 17%), 20% (95% CI: 14%, 28%), and 31% (95% CI: 15%, 52%), respectively. Conclusions Our evidence suggests there is a biological baseline for metastatic OS at diagnosis, which is observed in countries with very high HDI. In countries with medium/ low HDI, where there are more barriers to accessing healthcare, the higher prevalence of metastasis may result from treatment delay or an artificial prevalence inflation due to patients with less severe symptoms not presenting to clinic. Additional research in countries with medium/ low HDI may reveal that earlier detection and treatment could improve patient outcomes in those countries.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Prevalence of Metastasis at Diagnosis of Osteosarcoma: An International Comparison

Marko

Diessner

Spector

2016

Pediatric Blood & Cancer

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“…The role of chemotherapy in elderly patients has remained controversial. Several studies have shown that the currently available systemic chemotherapies are not effective in the elderly patients . However, some reports do suggest the benefits of chemotherapy in elderly patients with osteosarcoma .…”

Section: Discussionmentioning

confidence: 99%

“…The differences include a more frequent involvement of the axial bones, a lower tolerance to aggressive chemotherapy, and often secondary to Paget's disease or radiation therapy . Secondary osteosarcoma was reported as accounting for one‐third to one‐half of all elderly patients with osteosarcoma, while the corresponding figures in Asian population has been reported to range from 12.6% to 22% . Elderly patients with primary osteosarcoma tend to respond poorly to chemotherapy .…”

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confidence: 99%

Establishment and characterization of a novel osteosarcoma cell line: CHOS

Liu¹,

Feng²,

Zhang³

et al. 2016

Journal Orthopaedic Research

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Osteosarcoma has a well-recognized bimodal distribution, with the first peak in adolescence and another in the elderly age-group. The elderly patients have different clinical features and a poorer prognosis as compared to adolescents. To better understand the biological features of osteosarcoma in the elderly population, we established a new human osteosarcoma cell line from a 58-year-old man with primary chondroblastic osteosarcoma. After 6 months of continuous culture in vitro for over 50 passages, an immortalized cell line CHOS was established. The cell line was well-characterized by cytogenetic, biomarker, functional, and histological analyses. The CHOS cells exhibited a spindle-shaped morphology and a doubling time of 36 h. Cytogenetic analysis of CHOS cells revealed the loss of chromosome Y and the gain of chromosome 12. Quantitative real-time polymerase chain reaction (RT-PCR), Western blotting and/or immunofluorescence revealed the expression of chondroblastic, mesenchymal and tumor metastasis markers in the CHOS cells. Compared with the osteosarcoma cell line, the CHOS cells were found to be more sensitive to cisplatin and doxorubicin, but were resistant to methotrexate. The cell line was highly tumorigenic and maintained the histological characteristics and invasive nature of the original tumor. Furthermore, on immunohistochemical analysis, the xenografts and metastases were found to co-express collagen II, aggrecan, vimentin and S100A4 that resembled the original tumor cells. Our results indicate, the potential of CHOS cell line to serve as a useful tool for further studies on the molecular biology of osteosarcoma, especially in the elderly patients. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2116-2125, 2016.

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“…In pediatric patients with localized disease, ~80-90% of 5-year overall survival is achieved when treated at experienced centers (3)(4)(5); however, in adult patients (6,7) and patients with recurrent or metastatic disease (3,8,9), response to chemotherapy is less satisfactory, and survival of such patients is generally poor.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic mechanism of PLK1 inhibitor GSK461364 against osteosarcoma: Mitotic arrest, apoptosis, cellular senescence, and synergistic effect with paclitaxel

Chou

Yen

Chen

et al. 2016

International Journal of Oncology

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Abstract. Polo-like kinase 1 (PLK1), a serine/threonine kinase and an oncogene, is crucial in regulating cell cycle progression. PLK1 also has been demonstrated as a potential target of osteosarcoma (OS) by using short hairpin RNA libraries in lentiviral vectors for screening of protein kinase. In preclinical studies, GSK461364, a potent and selective ATP-competitive PLK1 inhibitor, showed antiproliferative activity against multiple tumor cell lines. In the present study, we evaluated the expression level of PLK1 in OS and explored the cytotoxic mechanism of GSK461364 against OS. PLK1 was significantly overexpressed in OS compared with normal osteoblasts and other types of sarcoma. GSK461364 inhibited PLK1 and caused mitotic arrest by inducing G2/M arrest in OS cells. Moreover, GSK461364 exerted a cytotoxic effect by inducing apoptosis in OS, and induced cellular senescence in OS cell lines, as indicated by an increased senescenceassociated β-galactosidase activity and enhanced DcR2 and interleukin-1α expression. In addition, we demonstrated a synergistic cytotoxic effect of GSK461364 and paclitaxel, possibly resulting from combined mitotic arrest. In conclusion, the present study revealed that PLK1 was overexpressed in OS and that GSK461364 exerted its cytotoxic effect on OS by inducing mitotic arrest and subsequent apoptosis and induced cellular senescence; therefore, senescence-associated markers can be used as treatment biomarkers, and a combination of GSK461364 and paclitaxel can potentially treat OS.

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Osteosarcoma in Asian Populations Over the Age of 40 Years: A Multicenter Study

Cited by 36 publications

References 22 publications

Prevalence of Metastasis at Diagnosis of Osteosarcoma: An International Comparison

Prevalence of Metastasis at Diagnosis of Osteosarcoma: An International Comparison

Establishment and characterization of a novel osteosarcoma cell line: CHOS

Cytotoxic mechanism of PLK1 inhibitor GSK461364 against osteosarcoma: Mitotic arrest, apoptosis, cellular senescence, and synergistic effect with paclitaxel

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