A comparative in vivo study of hyperthermic intraperitoneal chemotherapy with cisplatin versus doxorubicin versus cisplatin plus doxorubicin for the treatment of intra-abdominally disseminated alveolar rhabdomyosarcoma in mice

IF 2.4 3区医学 Q2 HEMATOLOGY

Pediatric Blood & Cancer Pub Date : 2024-10-07 DOI:10.1002/pbc.31366

Illya Martynov, Jens Gesche, Lajwanti Dhaka, Luca Tobi, Paul Hoyer, Guido Seitz

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引用次数: 0

Abstract

Background

Treatment options for advanced intra-abdominal pediatric rhabdomyosarcoma (RMS) with peritoneal sarcomatosis (PS) include cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). However, optimal dosages and combination regimens of drugs used for HIPEC are underexplored. We aimed to evaluate the efficacy of HIPEC with cisplatin, doxorubicin, and their combination in vivo.

Methods

We established PS/RMS mouse model by intraperitoneally injecting RH30 cells into NOD/LtSz-scid IL2Rγ-null mice. Two weeks post xenotransplantation, mice underwent a single HIPEC procedure at 42°C for 60 minutes. Treatment groups received cisplatin (50, 100, and 150 mg/m²) and doxorubicin (30, 45, and 60 mg/m²), administered alone or combined. The control group underwent an intraperitoneal lavage with isotonic saline. Peritoneal cancer index (PCI) was used to quantify the extent of peritoneal tumor spread. Tissue samples were evaluated regarding proliferation (Ki-67) and apoptosis (caspase 3).

Results

Mice treated with cisplatin at 100 mg/m² (PCI of 3.875, p = .007) and 150 mg/m² (PCI of 4.556, p = .026), and doxorubicin at 30 mg/m² (PCI of 2.875, p < .001) and 45 mg/m² (PCI of 4.143, p = .021) showed reduced PCI, with the combination of cisplatin 50 mg/m² and doxorubicin 30 mg/m² showing the most prominent effect (PCI of 3.333, p < .001) compared to the control group (PCI of 8.615). Histologically, there was no difference in Ki-67 or caspase 3 expression among the groups.

Conclusions

The cisplatin- and doxorubicin-based HIPEC significantly reduces peritoneal tumor dissemination in vivo. Further investigations are needed to explore the underlying molecular responses to optimize therapeutic strategies.

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用顺铂和多柔比星与顺铂加多柔比星的腹腔热化疗治疗小鼠腹腔播散性肺泡横纹肌肉瘤的体内对比研究。

背景：晚期腹腔内小儿横纹肌肉瘤（RMS）合并腹膜肉瘤病（PS）的治疗方案包括细胞还原手术（CRS）和腹腔内热化疗（HIPEC）。然而，HIPEC的最佳用药剂量和联合用药方案尚未得到充分探索。我们的目的是评估顺铂、多柔比星及其联合用药在体内HIPEC的疗效：方法：我们将 RH30 细胞腹腔注射到 IL2Rγ 缺失的 NOD/LtSz-scid 小鼠体内，建立了 PS/RMS 小鼠模型。异种移植两周后，小鼠在 42°C 下接受 60 分钟的单次 HIPEC 治疗。治疗组接受顺铂（50、100和150毫克/平方米）和多柔比星（30、45和60毫克/平方米）单独或联合给药。对照组用等渗生理盐水进行腹腔灌洗。腹膜癌指数（PCI）用于量化腹膜肿瘤扩散的程度。对组织样本的增殖（Ki-67）和凋亡（caspase 3）进行评估：结果：用 100 毫克/平方米（PCI 为 3.875，p = .007）和 150 毫克/平方米（PCI 为 4.556，p = .026）的顺铂和 30 毫克/平方米（PCI 为 2.875，p 2（PCI 为 4.143，p = .021）的多柔比星治疗小鼠后，PCI 有所降低，其中顺铂 50 毫克/平方米和多柔比星 30 毫克/平方米的组合效果最显著（PCI 为 3.333，p 结论）：以顺铂和多柔比星为基础的HIPEC能显著减少腹膜肿瘤在体内的扩散。为优化治疗策略，还需进一步研究潜在的分子反应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pediatric Blood & Cancer 医学-小儿科

CiteScore

4.90

自引率

9.40%

发文量

546

审稿时长

1.5 months

期刊介绍： Pediatric Blood & Cancer publishes the highest quality manuscripts describing basic and clinical investigations of blood disorders and malignant diseases of childhood including diagnosis, treatment, epidemiology, etiology, biology, and molecular and clinical genetics of these diseases as they affect children, adolescents, and young adults. Pediatric Blood & Cancer will also include studies on such treatment options as hematopoietic stem cell transplantation, immunology, and gene therapy.