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纳武单抗在小鼠模型恶性黑色素瘤腹膜转移中的作用

Effects of nivolumab in peritoneal carcinamatosis of malign melanoma in mouse model.

作者信息

Duzgun Ozgul, Sarici Inanc Samil, Gokcay Serkan, Ates Kivilcim Eren, Yılmaz Mehmet Bertan

机构信息

MD, Department of Surgical Oncology, Umraniye Training and Research Hospital, Istanbul, Turkey. Conception, design, scientific, and intellectual content of the study; technical procedures.

MD, Department of General Surgery, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey. Statistical analysis, manuscript writing, final approval.

出版信息

Acta Cir Bras. 2017 Dec;32(12):1006-1012. doi: 10.1590/s0102-865020170120000002.

DOI:10.1590/s0102-865020170120000002
PMID:29319729
Abstract

PURPOSE

To evaluate the efficacy of nivolumab and comparison with dacarbazine (DTIC) on peritoneal carcinomatosis of malignant melanoma in mouse model.

METHODS

Mouse skin melanoma cells was injected under the capsule of the peritoneal surface in the left side of the abdomen. On postoperative day ten, mouses randomised into three groups. Group 1: Control, Group 2: HIPEC (Hyperthermic intraperitoneal chemotherapy) with DTIC and Group 3: HIPEC with Nivolumab. After the sacrification on postoperative day fifteen, peritoneum evaluated macroscopically and histopathologically by using peritoneal regression grading score (PRGS).

RESULTS

In the 15th day exploration, all animals developed extensive intraperitoneal tumor growth in Group 1. In Group 2 and Group 3 median tumor size was 0.7±0.3cm and 0.3±0.2cm respectively (p: 0.023). Peritoneal carcinomatosis index (PCI) were significantly lower in Group 3 than other groups (p: 0.019). The lowest total tumor nodules in group 3 was 4 ± 2. The PGRS score was found significantly lower in Group 3 than other groups (p: 0.03). Lymphocytic response rate was found higher in the Group 3.

CONCLUSIONS

It has been found that nivolumab significantly better than DTIC on peritoneal metastases of malign melanoma in mouse models. Nivolumab treatment gives promising results with pathological evidence in the treatment of metastatic disease of malignant melanoma.

摘要

目的

在小鼠模型中评估纳武单抗治疗恶性黑色素瘤腹膜转移癌的疗效,并与达卡巴嗪(DTIC)进行比较。

方法

将小鼠皮肤黑色素瘤细胞注射到腹部左侧腹膜表面包膜下。术后第10天,将小鼠随机分为三组。第1组:对照组;第2组:采用DTIC的腹腔热灌注化疗(HIPEC)组;第3组:采用纳武单抗的HIPEC组。术后第15天处死小鼠后,通过腹膜消退分级评分(PRGS)对腹膜进行宏观和组织病理学评估。

结果

在第15天的探查中,第1组所有动物均出现广泛的腹腔内肿瘤生长。第2组和第3组的肿瘤中位数大小分别为0.7±0.3cm和0.3±0.2cm(p:0.023)。第3组的腹膜癌指数(PCI)明显低于其他组(p:0.019)。第3组的总肿瘤结节数最低,为4±2。发现第3组的PGRS评分明显低于其他组(p:0.03)。第3组的淋巴细胞反应率较高。

结论

已发现纳武单抗在小鼠模型中治疗恶性黑色素瘤腹膜转移方面明显优于DTIC。纳武单抗治疗在恶性黑色素瘤转移性疾病的治疗中取得了有病理证据支持的 promising 结果。 (注:“promising”直译为“有希望的”,结合语境这里用“良好”等词替代可能更合适,但按要求未做修改)

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