AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan.
AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA.
Biomed Pharmacother. 2019 Mar;111:835-840. doi: 10.1016/j.biopha.2018.12.110. Epub 2019 Jan 4.
Undifferentiated/unclassified soft-tissue sarcomas (USTS) is recalcitrant neoplasms that is usually treated with doxorubicin (DOX)-containing regimens as first-line therapy. Nanoparticle albumin-bound paclitaxel (nab-PTX) is a nanotechnology-based drug and is widely used in pancreatic cancer in combination with gemcitabine (GEM). The major goal of the present study was to determine the efficacy of nab-PTX in combination with GEM, compared to conventional drugs such as docetaxel (DOC), GEM combined with DOC, or first-line drug DOX on a USTS not-otherwise specified (USTS/NOS) from a striated muscle implanted in the right biceps femoris muscle of nude mice to establish a patient-derived orthotopic xenograft (PDOX) model. USTS PDOX models were randomized into six groups: untreated control; DOX; DOC; nab-PTX; GEM combined with DOC; and GEM combined with nab-PTX. Tumor size and body weight were measured. Tumor growth was inhibited to the greatest extent by GEM combined with nab-PTX. Tumors treated with GEM combined with nab-PTX had the most necrosis. Body weight of the treated mice was not significantly different from the untreated controls. The present study demonstrates the power of the PDOX model to identify a novel effective treatment strategy of the combination of GEM and nab-PTX for recalcitrant soft-tissue sarcomas. These results suggest that combination of GEM and nab-PTX could be a promising therapeutic strategy for USTS.
未分化/未分类软组织肉瘤（USTS）是一种难治性肿瘤，通常采用含多柔比星（DOX）的方案作为一线治疗。纳米白蛋白结合紫杉醇（nab-PTX）是一种基于纳米技术的药物，广泛用于联合吉西他滨（GEM）治疗胰腺癌。本研究的主要目的是确定 nab-PTX 联合 GEM 与传统药物（如多西紫杉醇（DOC）、DOC 联合 GEM 或一线药物 DOX）治疗右股二头肌植入的 USTS/NOS（未另作说明）的疗效，以建立一个患者来源的原位异种移植（PDOX）模型。将 USTS PDOX 模型随机分为六组：未治疗对照组；DOX；DOC；nab-PTX；GEM 联合 DOC；和 GEM 联合 nab-PTX。测量肿瘤大小和体重。GEM 联合 nab-PTX 抑制肿瘤生长的效果最显著。用 GEM 联合 nab-PTX 治疗的肿瘤坏死最多。治疗小鼠的体重与未治疗对照组无显著差异。本研究证明了 PDOX 模型在确定吉西他滨联合 nab-PTX 治疗难治性软组织肉瘤的新有效治疗策略方面的强大作用。这些结果表明，GEM 联合 nab-PTX 可能是 USTS 的一种有前途的治疗策略。
