High-Dose Chemotherapy in the Treatment of Relapsed Osteosarcoma: An Italian Sarcoma Group Study

Fagioli, Franca; Aglietta, Massimo; Tienghi, A.; Ferrari, Stefano; Prever, A Brach del; Vassallo, Elena; Palmero, Alessandra; Biasin, Eleonora; Bacci, Gaetano; Picci, Piero; Madon, E

doi:10.1200/jco.2002.08.081

Cited by 131 publications

(83 citation statements)

References 38 publications

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“…Patients who received standard chemotherapy before and after surgery and then radiation had the 5-year survival rate of 60-70% (Sampson et al 2015). Moreover, patients with metastatic and advanced tumors have only 23 months of median survival time (Fagioli et al 2002). Current clinical trials have not improved the overall survival of osteosarcoma patients, and the understanding of molecular pathogenesis of osteosarcoma is limited.…”

Section: Introductionmentioning

confidence: 99%

Transcription Factor SOX9 Promotes Osteosarcoma Cell Growth by Repressing Claudin-8 Expression [Retraction]

Yang

Hao

et al. 2017

Tohoku J. Exp. Med.

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Osteosarcoma is a malignant bone cancer that mainly affects children. SOX9 plays a key role in bone formation and osteosarcoma, and Claudin-8 (CLDN8), a tight junction protein, contributes to proliferation of osteosarcoma cells. The aim of this study was to investigate the relationship between SOX9 and CLDN8 in osteosarcoma. The expression levels of SOX9 and CLDN8 were determined in osteosarcoma specimens (n = 25) by qRT-PCR and Western blot analyses. The levels of SOX9 mRNA and protein were significantly higher in osteosarcoma tissues than those in adjacent non-tumor tissues, whereas the expression levels of CLDN8 mRNA and protein were significantly lower in osteosarcoma tissues. Immunohistochemical analysis showed the high expression of SOX9 in 56 out of 97 osteosarcoma tissues (57.7%). By contrast, the low expression of immunoreactive CLDN8 was observed in 62 of 97 osteosarcoma tissues (63.9%). There was the inverse correlation between the expression levels of SOX9 and CLDN8 proteins (R = −0.633, P < 0.001). The overall survival was poorer in the patients with high SOX9 expression. Subsequently, using two human osteosarcoma cell lines, we showed that knockdown of SOX9 inhibited cell proliferation and migration but promoted cell apoptosis. Importantly, knockdown of SOX9 increased the expression levels of CLDN8 protein. The transient luciferase-reporter assays suggest that SOX9 may inhibit the promoter activity of the CLDN8 gene in osteosarcoma cells. In conclusion, we provide the evidence demonstrating that SOX9 may promote cell growth by repressing the expression of CLDN8. Thus, SOX9 may be a therapeutic target for osteosarcoma.

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Section: Introductionmentioning

confidence: 99%

Transcription Factor SOX9 Promotes Osteosarcoma Cell Growth by Repressing Claudin-8 Expression [Retraction]

Yang

Hao

et al. 2017

Tohoku J. Exp. Med.

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“…9,10 Although methotrexate, doxorubicin, cisplatin and ifosfamide were shown to be active agents in osteosarcoma, their uses in high doses are limited owing to their toxicities. 11 However, high doses of etoposide and carboplatin have been shown to have antitumor effect with suitable toxicity profiles.…”

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confidence: 99%

“…11 However, high doses of etoposide and carboplatin have been shown to have antitumor effect with suitable toxicity profiles. 9,12 Previous studies on HDCT and ASCT in osteosarcoma used heterogeneous conditioning regimens and showed varying outcomes. 3,13,14 The current analysis of high-risk osteosarcoma patients treated with HDCT and ASCT with a uniform conditioning regimen MEC at our institute showed promising results.…”

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confidence: 99%

High-dose chemotherapy and autologous stem cell transplantation with melphalan, etoposide and carboplatin for high-risk osteosarcoma

et al. 2015

Bone Marrow Transplant

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“…3,4,5 The tumor necrosis rate may be increased by multiple drug combinations, whereas HDC is found to be the most effective way of increasing the response rate among other conventional therapy modalities. HDC and APBSCT were reported previously to be used predominantly in metastatic osteosarcoma 7,8 and in various bone tumors with a poor prognosis. 9 In the current study, we examined the feasibility of HDC in patients with nonmetastatic, high-grade osteosarcoma.…”

Section: Discussionmentioning

confidence: 99%

“…Hovewer, peripheral blood stem cell support can decrease the myelosupressive toxicities in several tumors, including sarcomas. 6 High-dose chemotherapy (HDC) and autologous peripheral blood stem cell support or transplantation (APBSCT) were reported to be the dominant modalities used in patients with metastatic osteosarcoma 7,8 and various bone tumors with poor prognosis. 9 In the current study, we planned to harvest and transplant PBSC after two cycles of an induction chemotherapy regimen.…”

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confidence: 99%

The feasibility of neoadjuvant high‐dose chemotherapy and autologous peripheral blood stem cell transplantation in patients with nonmetastatic high grade localized osteosarcoma

Arpacı

Ataergin

Özet

et al. 2005

Cancer

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BACKGROUNDThe primary and secondary objectives of the current study were to improve the ≥ 90% tumor necrosis rate and assess the toxicity profile of the neoadjuvant high‐dose chemotherapy (HDC) regimen, respectively.METHODSTwenty‐two patients with AJCC Stage IIB high‐grade osteosarcoma were included in the current study. Two cycles of an induction chemotherapy regimen including cisplatin, doxorubicin, and ifosfamide followed by HDC and autologous peripheral blood stem cell support or transplantation (APBSCT) were given. After engraftment was achieved, the patients underwent limb‐sparing surgery (LSS) followed by three to six cycles of postoperative chemotherapy depending on the tumor necrosis rate.RESULTSThe median follow‐up, the total duration of treatment, and the time to surgery were 23.7 months, 5.96 months, and 3.03 months, respectively. The necrosis rate was at least 90% in 82% of the cases. The 3‐year overall survival (OS) and disease‐free survival (DFS) rates were 83% and 70%, respectively. Leukopenia, anemia, thrombocytopenia, nausea and emesis, and mucositis were the most frequent Grade 3 and Grade 4 toxicities (according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) of induction, high‐dose, and adjuvant chemotherapies. At the time of last follow‐up, no patient had died of chemotherapeutic toxicity. LSS was performed in all patients. Surgery‐related complications were reported in 3 of 22 patients. Functional scoring results were excellent in eight patients, good in nine patients, fair in two patients, and poor in three patients.CONCLUSIONSThe results of the current Phase II study suggest that neoadjuvant HDC provides a greater than 90% necrosis rate with acceptable toxicity. A short duration of therapy and the feasibility of LSS in all patients are additional advantages of this approach. Cancer 2005. © 2005 American Cancer Society.

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High-Dose Chemotherapy in the Treatment of Relapsed Osteosarcoma: An Italian Sarcoma Group Study

Cited by 131 publications

References 38 publications

Transcription Factor SOX9 Promotes Osteosarcoma Cell Growth by Repressing Claudin-8 Expression [Retraction]

Transcription Factor SOX9 Promotes Osteosarcoma Cell Growth by Repressing Claudin-8 Expression [Retraction]

High-dose chemotherapy and autologous stem cell transplantation with melphalan, etoposide and carboplatin for high-risk osteosarcoma

The feasibility of neoadjuvant high‐dose chemotherapy and autologous peripheral blood stem cell transplantation in patients with nonmetastatic high grade localized osteosarcoma

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