Okada Seiji, Boonnate Piyanard, Panaampon Jutatip, Saisuwan Krittamate, Ogata-Aoki Hiromi, Abe Makoto, Hirabayashi Kaoru, Nakagawa Rumi, Kikuta Kazutaka
Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, JPN.
Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok, THA.
Cureus. 2024 Nov 29;16(11):e74781. doi: 10.7759/cureus.74781. eCollection 2024 Nov.
Soft tissue and bone tumors are rare, and their low frequency and diverse histological types make conducting large-scale clinical trials challenging. Patient-derived xenografts (PDX), entailing implantation of cancer specimens in immunocompromised mice, are emerging as a valuable translational model because PDX keeps the original tumors' character and drug sensitivity. We sequentially transplanted 166 surgical and biopsy specimens from orthopedic surgeries, including 138 soft tissue and bone tumors (81 malignant, 23 intermediate, and 34 benign), 16 metastatic bone tumors, 9 hematological malignancies, and 3 non-tumor tissues. Every specimen was cutaneously transplanted into both flanks of BALB/c Rag-2/Jak3 double deficient (BRJ) mice, and tumor formation was observed for up to 6 months. We defined PDX models as successfully generated if the tumors were passaged more than three times while retaining the histological characteristics of the original tumor. The rates of PDX generation were 28.1% (39/138) for all soft tissue and bone tumors, 42.6% (35/81) for malignant tumors, 4.3% (1/23) for intermediate tumors, and 8.8% (3/34) for benign tumors. Our models of PDX would be a useful platform for soft tissue and bone tumor precision medicine.
软组织和骨肿瘤较为罕见，其低发病率和多样的组织学类型使得开展大规模临床试验颇具挑战性。患者来源的异种移植模型（PDX），即将癌症标本植入免疫缺陷小鼠体内，正逐渐成为一种有价值的转化模型，因为PDX保留了原始肿瘤的特征和药物敏感性。我们相继移植了166份来自骨科手术的手术和活检标本，其中包括138例软组织和骨肿瘤（81例恶性、23例中间型和34例良性）、16例转移性骨肿瘤、9例血液系统恶性肿瘤以及3份非肿瘤组织。每份标本均经皮移植到BALB/c Rag-2/Jak3双缺陷（BRJ）小鼠的双侧胁腹，并观察肿瘤形成情况长达6个月。如果肿瘤能够传代超过三次，同时保留原始肿瘤的组织学特征，我们则定义为成功构建了PDX模型。所有软组织和骨肿瘤的PDX模型构建率为28.1%（39/138），恶性肿瘤为42.6%（35/81），中间型肿瘤为4.3%（1/23），良性肿瘤为8.8%（3/34）。我们构建的PDX模型将成为软组织和骨肿瘤精准医学的一个有用平台。
