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
Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014 Meldola (FC), Italy.
Ther Adv Med Oncol. 2017 Dec;9(12):755-767. doi: 10.1177/1758834017737472. Epub 2017 Oct 28.
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.
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.
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.
Our results provide a starting point for further research aimed at improving the management of MFS patients undergoing chemotherapy.
黏液纤维肉瘤（MFS）曾被认为是恶性纤维组织细胞瘤的黏液样变体，是成人四肢最常见的肉瘤，其特点是局部复发频率高。MFS的临床行为不可预测，化疗疗效仍未得到充分证实。此外，鉴于MFS作为一种独特病理实体的认识相对较新，其细胞和分子生物学在患者来源的临床前模型中仍未得到广泛研究。我们研究了高级别、患者来源的MFS原代培养物的分子生物学和治疗结果。
共分析了三种患者来源的MFS原代培养物。我们评估了CD109表达的作用，并寻找转化生长因子-β（TGF-β）表达与原代培养物对不同药物敏感性之间的相关性。
CD109是识别更具侵袭性的高级别MFS的有前景的标志物和潜在治疗靶点。结果还突出了TGF-β在化疗耐药中的潜在作用。药理学分析证实了培养物对化疗的敏感性。最有效的治疗方法是单独使用表柔比星以及表柔比星与异环磷酰胺联合使用，后者是包括MFS在内的软组织肉瘤（STS）当前的护理标准。
我们的结果为进一步研究提供了一个起点，旨在改善接受化疗的MFS患者的管理。
