Myxofibrosarcoma primary cultures: molecular and pharmacological profile

Alessandro De Vita, Federica Recine, Laura Mercatali, Giacomo Miserocchi, Chiara Liverani, Chiara Spadazzi, Roberto Casadei, Alberto Bongiovanni, Federica Pieri, Nada Riva, Dino Amadori, Toni Ibrahim

Research output: Contribution to journalArticle

Abstract

Background: Myxofibrosarcoma (MFS), formerly considered as a myxoid variant of malignant fibrous histiocytoma, is the most common sarcoma of the extremities in adults and is characterized by a high frequency of local recurrence. The clinical behavior of MFS is unpredictable and the efficacy of chemotherapy is still not well documented. Furthermore, given the relatively recent recognition of MFS as a distinct pathologic entity its cellular and molecular biology has still not been extensively studied in patient-derived preclinical models. We examined the molecular biology and treatment outcomes of high-grade, patient-derived MFS primary cultures.

Methods: A total of three patient-derived MFS primary cultures were analyzed. We evaluated the role of CD109 expression and also looked for a correlation between transforming growth factor-beta (TGF-β) expression and sensitivity of the primary cultures to different drugs.

Results: CD109 was a promising marker for the identification of more aggressive high-grade MFS and a potential therapeutic target. The results also highlighted the potential role of TGF-β in chemoresistance. Pharmacological analysis confirmed the sensitivity of the cultures to chemotherapy. The most active treatments were epirubicin alone and epirubicin in combination with ifosfamide, the latter representing the current standard of care for soft tissue sarcomas (STSs), including MFS.

Conclusions: Our results provide a starting point for further research aimed at improving the management of MFS patients undergoing chemotherapy.

Original languageEnglish
Pages (from-to)755-767
Number of pages13
JournalTherapeutic Advances in Medical Oncology
Volume9
Issue number12
DOIs
Publication statusPublished - Dec 2017

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Pharmacology
Epirubicin
Drug Therapy
Sarcoma
Transforming Growth Factor beta
Molecular Biology
Malignant Fibrous Histiocytoma
Ifosfamide
Standard of Care
Cell Biology
Extremities
Recurrence
Therapeutics
Research
Pharmaceutical Preparations

Keywords

  • Journal Article

Cite this

Myxofibrosarcoma primary cultures : molecular and pharmacological profile. / De Vita, Alessandro; Recine, Federica; Mercatali, Laura; Miserocchi, Giacomo; Liverani, Chiara; Spadazzi, Chiara; Casadei, Roberto; Bongiovanni, Alberto; Pieri, Federica; Riva, Nada; Amadori, Dino; Ibrahim, Toni.

In: Therapeutic Advances in Medical Oncology, Vol. 9, No. 12, 12.2017, p. 755-767.

Research output: Contribution to journalArticle

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AU - De Vita, Alessandro

AU - Recine, Federica

AU - Mercatali, Laura

AU - Miserocchi, Giacomo

AU - Liverani, Chiara

AU - Spadazzi, Chiara

AU - Casadei, Roberto

AU - Bongiovanni, Alberto

AU - Pieri, Federica

AU - Riva, Nada

AU - Amadori, Dino

AU - Ibrahim, Toni

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N2 - Background: Myxofibrosarcoma (MFS), formerly considered as a myxoid variant of malignant fibrous histiocytoma, is the most common sarcoma of the extremities in adults and is characterized by a high frequency of local recurrence. The clinical behavior of MFS is unpredictable and the efficacy of chemotherapy is still not well documented. Furthermore, given the relatively recent recognition of MFS as a distinct pathologic entity its cellular and molecular biology has still not been extensively studied in patient-derived preclinical models. We examined the molecular biology and treatment outcomes of high-grade, patient-derived MFS primary cultures.Methods: A total of three patient-derived MFS primary cultures were analyzed. We evaluated the role of CD109 expression and also looked for a correlation between transforming growth factor-beta (TGF-β) expression and sensitivity of the primary cultures to different drugs.Results: CD109 was a promising marker for the identification of more aggressive high-grade MFS and a potential therapeutic target. The results also highlighted the potential role of TGF-β in chemoresistance. Pharmacological analysis confirmed the sensitivity of the cultures to chemotherapy. The most active treatments were epirubicin alone and epirubicin in combination with ifosfamide, the latter representing the current standard of care for soft tissue sarcomas (STSs), including MFS.Conclusions: Our results provide a starting point for further research aimed at improving the management of MFS patients undergoing chemotherapy.

AB - Background: Myxofibrosarcoma (MFS), formerly considered as a myxoid variant of malignant fibrous histiocytoma, is the most common sarcoma of the extremities in adults and is characterized by a high frequency of local recurrence. The clinical behavior of MFS is unpredictable and the efficacy of chemotherapy is still not well documented. Furthermore, given the relatively recent recognition of MFS as a distinct pathologic entity its cellular and molecular biology has still not been extensively studied in patient-derived preclinical models. We examined the molecular biology and treatment outcomes of high-grade, patient-derived MFS primary cultures.Methods: A total of three patient-derived MFS primary cultures were analyzed. We evaluated the role of CD109 expression and also looked for a correlation between transforming growth factor-beta (TGF-β) expression and sensitivity of the primary cultures to different drugs.Results: CD109 was a promising marker for the identification of more aggressive high-grade MFS and a potential therapeutic target. The results also highlighted the potential role of TGF-β in chemoresistance. Pharmacological analysis confirmed the sensitivity of the cultures to chemotherapy. The most active treatments were epirubicin alone and epirubicin in combination with ifosfamide, the latter representing the current standard of care for soft tissue sarcomas (STSs), including MFS.Conclusions: Our results provide a starting point for further research aimed at improving the management of MFS patients undergoing chemotherapy.

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