Prognosis of Osteosarcoma With Pulmonary Metastases at Initial Presentation Is Not Dismal

Yonemoto, Tsukasa; Tatezaki, Shin-ichiro; Ishii, Takeshi; Satoh, Tetsuzo; Kimura, Hideki; Iwai, Naomichi

doi:10.1097/00003086-199804000-00024

Cited by 53 publications

(41 citation statements)

References 10 publications

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“…The survival curves demonstrated that, in patients with osteosarcoma, increased HMGB1 expression is associated with a poorer recurrence-free survival rate. The present study confirmed that the TNM stage and tumor size were predictive prognostic markers for the recurrence-free survival rate in patients with osteosarcoma, which was consistent with the findings of previous studies (6,46,47). Cox's multivariate regression revealed that independent prognostic factors for osteosarcoma consisted of tumor stage, tumor grade and HMGB1 reactivity, while the age and tumor size were not prognostic factors.…”

Section: Hmgb1 Staining ---------------------------------------------supporting

confidence: 92%

Expression of high mobility group box 1 protein predicts a poorer prognosis for patients with osteosarcoma

Zhang

et al. 2015

Oncology Letters

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Abstract. The high mobility group box 1 (HMGB1) protein functions as an extracellular signaling molecule that is critical in inflammation and carcinogenesis. The HMGB1 protein is actively secreted by natural killer cells, monocytes and macrophages, and acts as an inflammatory cytokine. The present study enrolled 174 patients that underwent a tumorectomy between 2006 and 2013 in Shandong Provincial Hospital. The age of the patients ranged between 13 and 74 years, with a median age of 27 years. The tumors of the patients were staged according to the Union for International Cancer Control 2009 tumor-node-metastasis tumor staging system. Nuclear grading was based on the Fuhrman grading system. In the osteosarcoma tissue samples, HMGB1 expression was detected in 84 samples (48.3%) with a low immunoreactivity and in 90 samples (51.7%) with a high immunoreactivity. The association between clinicopathological characteristics and tumor cell HMGB1 expression (low vs. high) was summarized. The association between HMGB1 expression and tumor size, tumor stage and nuclear grade was statistically significant (P=0.034, 0.008 and 0.019, respectively). There was no significant association between HMGB1 expression and the age of the patients (P= 0.335; Table I). The current study demonstrated that patients with a high HMGB1 expression (>50% cells expressing HMGB1) had poorer survival rates, and therefore a poorer prognosis, compared with patients with low HMGB1 immunostaining (10-50% cells expressing HMGB1). The results of the present study suggest that higher expression levels of HMGB1 are significantly associated with a poorer prognosis and may act as a marker for prognosis in osteosarcoma, particularly osteosarcoma recurrence. Additional studies investigating the biological features of HMGB1 may confirm the potential role of HMGB1 as a novel target for anticancer therapy in osteosarcoma.

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Section: Hmgb1 Staining ---------------------------------------------supporting

confidence: 92%

Expression of high mobility group box 1 protein predicts a poorer prognosis for patients with osteosarcoma

Zhang

et al. 2015

Oncology Letters

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“…The genetic events that lead to the development and metastasis of OS are not known and may be a reflection of the complexity of OS (Letson and Muro-Cacho, 2001;Fuchs and Pritchard, 2002;Ragland et al, 2002). Although approximately 80% of OS patients have metastatic disease at the time of diagnosis, only 10-15% of these lesions are detectable with current radiographic imaging modalities (Yonemoto et al, 1998;Kaste et al, 1999). Therefore, there is a clinical need to identify genetic markers that not only provide insight into the pathogenesis of OS, but also its metastasis.…”

mentioning

confidence: 99%

Insulin-like growth factor binding protein 5 suppresses tumor growth and metastasis of human osteosarcoma

et al. 2011

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Osteosarcoma (OS) is the most common primary malignancy of bone. There is a critical need to identify the events that lead to the poorly understood mechanism of OS development and metastasis. The goal of this investigation is to identify and characterize a novel marker of OS progression. We have established and characterized a highly metastatic OS subline that is derived from the less metastatic human MG63 line through serial passages in nude mice via intratibial injections. Microarray analysis of the parental MG63, the highly metastatic MG63.2 subline, as well as the corresponding primary tumors and pulmonary metastases revealed insulin-like growth factor binding protein 5 (IGFBP5) to be one of the significantly downregulated genes in the metastatic subline. Confirmatory quantitative RT-PCR on 20 genes of interest demonstrated IGFBP5 to be the most differentially expressed and was therefore chosen to be one of the genes for further investigation. Adenoviral mediated overexpression and knockdown of IGFBP5 in the MG63 and MG63.2 cell lines, as well as other OS lines (143B and MNNG/HOS) that are independent of our MG63 lines, were employed to examine the role of IGFBP5. We found that overexpression of IGFBP5 inhibited in vitro cell proliferation, migration and invasion of OS cells. Additionally, IGFBP5 overexpression promoted apoptosis and cell cycle arrest in the G1 phase. In an orthotopic xenograft animal model, overexpression of IGFBP5 inhibited OS tumor growth and pulmonary metastases. Conversely, siRNA-mediated knockdown of IGFBP5 promoted OS tumor growth and pulmonary metastases in vivo. Immunohistochemical staining of patient-matched primary and metastatic OS samples demonstrated decreased IGFBP5 expression in the metastases. These results suggest 1) a role for IGFBP5 as a novel marker that has an important role in the pathogenesis of OS, and 2) that the loss of IGFBP5 function may contribute to more metastatic phenotypes in OS.

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“…The survival rate for patients can be as high as 60%-75% when both the primary tumor and the solitary lung metastasis are adequately resected (Yonemoto et al, 1997;Bacci et al, 2006). The rate of surgical site recurrence is 4% to 6% for both limb-salvage and amputations.…”

Section: Surgerymentioning

confidence: 99%

“…Pulmonary recurrence is most common secondary to micro-metastatic disease. Regardless of poor prognosis, repeated tumor excisions can be performed (of primary site or metastatic one), because many studies have shown improved survival rates (Yonemoto, 1997;Bacci et al, 2001). The role of "second-line" chemotherapy regimen remains controversial because no standard regimen exists for the recurrence of the tumor.…”

Section: Prognosismentioning

confidence: 99%

Effects of Neoadjuvant Chemotherapy in High-Grade Non-Metastatic Osteosarcoma of Extremities

Samardziski¹,

Janevska²,

Zafirova-Ivanovska³

et al. 2012

Neoadjuvant Chemotherapy - Current Applications in Clinical Practice

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Prognosis of Osteosarcoma With Pulmonary Metastases at Initial Presentation Is Not Dismal

Cited by 53 publications

References 10 publications

Expression of high mobility group box 1 protein predicts a poorer prognosis for patients with osteosarcoma

Expression of high mobility group box 1 protein predicts a poorer prognosis for patients with osteosarcoma

Insulin-like growth factor binding protein 5 suppresses tumor growth and metastasis of human osteosarcoma

Effects of Neoadjuvant Chemotherapy in High-Grade Non-Metastatic Osteosarcoma of Extremities

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