Dedifferentiated chondrosarcoma.

Capanna, Rodolfo; Bertoni, Francesco; Bettelli, G; Picci, Piero; Bacchini, P; Present, David; Giunti, A; Campanacci, Mario

doi:10.2106/00004623-198870010-00010

Cited by 99 publications

(65 citation statements)

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“…Several preclinical efforts are currently underway to develop targeted therapy for dedifferentiated chondrosarcoma based on molecular approaches [14,15,17]. The low survival rates of patients we observed with dedifferentiated chondrosarcoma are comparable to those reported in previous studies (Table 3) [3,5,9,10,13,18,21,22]. This indicates the need for more systemic options.…”

Section: Discussionsupporting

confidence: 84%

“…Studies performed to date have not identified efficacious chemotherapy agents [3,5,9,10,13,18,21,22]. We therefore sought to determine diseasespecific survivorship (as well as local recurrences and metastases), prognostic variables associated with patient survival, and toxicities associated with ifosfamide-based chemotherapy for patients diagnosed with dedifferentiated chondrosarcoma.…”

Section: Discussionmentioning

confidence: 99%

“…This is likely the result of the small number of patients in our study. Studies performed to date have not shown a significant prognostic impact of adjuvant chemotherapy in patients with dedifferentiated chondrosarcoma [3,5,9,10,13,18,21,22]. Ifosfamide has been identified as one of the active drugs for bone and soft tissue sarcomas and was incorporated into chemotherapeutic regimens for osteosarcoma in the 1980s [6,11,19].…”

Section: Discussionmentioning

confidence: 99%

“…Treatment of dedifferentiated chondrosarcoma remains a major challenge. As a result of the rarity of the disease, only two institutes [3,5,9,18,22] have reported the outcomes of more than 30 cases.…”

Section: Introductionmentioning

confidence: 99%

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Does Ifosfamide Therapy Improve Survival of Patients With Dedifferentiated Chondrosarcoma?

Kawaguchi

Sun²,

Lin

et al. 2014

Clinical Orthopaedics &Amp; Related Research

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Background Dedifferentiated chondrosarcoma remains a significant therapeutic challenge. Studies performed to date have not identified efficacious chemotherapy regimens for this disease. Questions/purposes We sought to (1) evaluate the disease-specific survival at 2 and 5 years of patients with dedifferentiated chondrosarcoma; (2) assess the prognostic variables (both patient-and treatment-related), including the use of chemotherapy with ifosfamide, that relate to survivorship; and (3) assess specific toxicities associated with ifosfamide use. Methods Data from 41 patients with dedifferentiated chondrosarcoma diagnosed and treated at the University of Texas MD Anderson Cancer Center from 1986 to 2010 were analyzed for demographics, treatments, oncologic outcomes, and prognostic variables. There were 14 women and 27 men. The mean age at diagnosis was 58 years (range, 26-86 years). Seven patients presented with metastasis. Surgical resection alone was performed in 11 patients; resection and chemotherapy in 26 patients; resection and radiotherapy in two patients; and resection, chemotherapy, and radiotherapy in two patients. Ifosfamide-based regimens were used for 16 patients. In general, ifosfamide was used when the tumor was located in the trunk or if cisplatin was discontinued as a result of toxicity. Minimum followup was 8 months (median, 68 months; range, 8-281 months). Survival was estimated using Kaplan-Meier plots and analyzed by using the Cox proportional hazards model. Results Disease-specific survival rates at 2 and 5 years were 33% and 15%, respectively. Multivariate analysis revealed that treatment without ifosfamide-based chemotherapy was the only independent negative prognostic factor for disease-specific survival (hazard ratio, 0.4; 95% confidence interval, 0.17-0.92; p = 0.03). Ifosfamide was discontinued in a patient as a result of renal dysfunction and was decreased in dose in another patient who developed encephalopathy. Conclusions In this small retrospective study, it appeared that ifosfamide-based adjuvant chemotherapy combined with surgical resection offered a treatment advantage compared with patients who did not receive the drug in Each author certifies that he or she, or a member of his or her immediate family, has no funding or commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request. Each author certifies that his or her institution approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained. This work was performed at

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Does Ifosfamide Therapy Improve Survival of Patients With Dedifferentiated Chondrosarcoma?

Kawaguchi

Sun²,

Lin

et al. 2014

Clinical Orthopaedics &Amp; Related Research

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“…Chondrosarcomas are difficult tumors to cure, because they are unresponsive to the standard adjuvant treatment, chemotherapy (3) and radiation therapy (4), resulting in cure rates of less than 10% (5,6), with the vast majority of patients succumbing to pulmonary metastases. Angiogenesis is critical for both tumor growth and development of metastases, and inhibiting angiogenesis has become a therapeutic strategy.…”

mentioning

confidence: 99%

HDAC4 Represses Vascular Endothelial Growth Factor Expression in Chondrosarcoma by Modulating RUNX2 Activity

Sun

Wei

Chen

et al. 2009

Journal of Biological Chemistry

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Chondrosarcoma is a primary bone tumor with a dismal prognosis; most patients with this disease develop fatal pulmonary metastases, suggesting the need for a better systemic treatment. Anti-angiogenesis treatment may be useful, because angiogenesis is critical for both tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is the most potent pro-angiogenic factor and is regulated by pathways related to the normal physiologic response to hypoxia and genetic alterations related to the malignant phenotype. Our prior work has shown that VEGF is overexpressed in high grade chondrosarcoma and chondrosarcoma cell lines. Working on the premise that developmental pathways giving a selective growth advantage are often recapitulated in tumors, we investigated the regulation of VEGF by HDAC4 and Runx2 in chondrosarcoma. We tested the hypothesis that there is dysregulation of HDAC4/Runx2/VEGF gene expression and that decreased HDAC4 expression accounts for at least some of the increased VEGF expression seen in chondrosarcoma. We show that reduced expression of HDAC4 in chondrosarcoma cells increases expression of Runx2 leading to increased expression of VEGF and in vitro angiogenesis. Thus, both hypoxia and dysregulated expression of a developmental pathway are causes of increased VEGF expression in chondrosarcoma.Chondrosarcomas are mesenchymal tumors in which the primary tissue is cartilage; they include 20% of primary bone tumors and occur in patients of all ages (1, 2). Chondrosarcomas are difficult tumors to cure, because they are unresponsive to the standard adjuvant treatment, chemotherapy (3) and radiation therapy (4), resulting in cure rates of less than 10% (5, 6), with the vast majority of patients succumbing to pulmonary metastases. Angiogenesis is critical for both tumor growth and development of metastases, and inhibiting angiogenesis has become a therapeutic strategy. We have demonstrated that grade II and III chondrosarcomas have more microvascularity than benign or grade I tumors (7) and that these tumors overexpress vascular endothelial growth factor (VEGF) 2 (8).Because VEGF is the most important proangiogenic molecule and is overexpressed in high grade chondrosarcoma, we have focused on the regulation of VEGF in this tumor. VEGF expression is determined by normal physiologic hypoxia-related pathways and genetic abnormalities. We know that both of these broad categories of gene regulation are operational in chondrosarcomas. Included in genetic abnormalities are epigenetic phenomena such as DNA methylation and histone modification that regulate chromatin structure and gene expression (9). Both histone acetylases and histone deacetylases (HDACs) are key enzymes that catalyze the reversible acetylation/deacetylation of core histone tails, which is an essential mechanism of the epigenetic control of gene expression (10). HDACs function as transcriptional co-repressors. HDACs can deacetylate DNA binding transcription factors, thereby decreasing their binding affinity, localization, and half-life...

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Is dedifferentiated chondrosarcoma a ?de-differentiated? chondrosarcoma?

Aigner

Unni

1999

J. Pathol.

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Since its first description 30 years ago, dedifferentiated chondrosarcoma has been the prototype of all dedifferentiated sarcomas. The presence of two tumour portions of different mesenchymal differentiation lineages in these neoplasms gives rise to three key questions, which are on the way to being resolved. Does it split up? And if so, how does it split up and when does it split up? Accumulating data provide evidence for a common monoclonal origin of both tumour portions and suggest that dedifferentiated chondrosarcoma is a paradigmatic neoplasm of mesenchymal transdifferentiaton in vivo. Two categories emerge of dedifferentiated chondrosarcomas with different cell biology: the classical one, with a low‐grade chondroid component splitting up late, and a second type, with a high‐grade chondroid component splitting up early in tumour development. Copyright © 1999 John Wiley & Sons, Ltd.

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Dedifferentiated chondrosarcoma.

Cited by 99 publications

References 0 publications

Does Ifosfamide Therapy Improve Survival of Patients With Dedifferentiated Chondrosarcoma?

Does Ifosfamide Therapy Improve Survival of Patients With Dedifferentiated Chondrosarcoma?

HDAC4 Represses Vascular Endothelial Growth Factor Expression in Chondrosarcoma by Modulating RUNX2 Activity

Is dedifferentiated chondrosarcoma a ?de-differentiated? chondrosarcoma?

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