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在兔腹膜癌模型中,腹腔镜下腹膜下注射载化疗药物微粒可降低肿瘤生长。

Laparoscopic subperitoneal injection of chemo-loaded particles lowers tumor growth on a rabbit model of peritoneal carcinomatosis.

作者信息

Pascale Florentina, Fazel Afshin, Namur Julien, Ghegediban Saida-Homayra, D'Inca Hadrian, Wassef Michel, Moine Laurence, Laurent Alexandre

机构信息

1 ArchimMed, Jouy en Josas, France.

2 Hôpital Lariboisière, Paris, France.

出版信息

Tumour Biol. 2017 May;39(5):1010428317698381. doi: 10.1177/1010428317698381.

Abstract

The purpose of our study was to assess the effect of controlled-release chemotherapy on the growth and viability of peritoneal carcinomatosis treated by subperitoneal injection in a rabbit VX2 model. A model of peritoneal carcinomatosis was created by laparoscopic injection of VX2 tumor in the left and right broad ligaments of 12 White New Zealand rabbits. At day 12, each tumor was randomly treated with a peritumoral injection of 0.5 mL microspheres loaded with doxorubicin (DEM-DOX) or unloaded (DEM-BLAND). Seven days after treatment, tumor volume, tumor viability in histology, local tumor necrosis in contact with DEM, and doxorubicin concentration profile around the drug eluting microspheres (DEM) were measured. Tumor volume was significantly lower in the DEM-DOX group (3.6 ± 3.2 cm) compared with the DEM-BLAND group (8.9 ± 5.4 cm) (p = 0.0425). The percentage of viable tumor tissue was significantly lower in the DEM-DOX group (38% ± 17%) compared with the DEM-BLAND group (56% ± 20%) (p = 0.0202). Tissue necrosis was observed around all DEM-DOX up to a distance of 1.094 ± 0.852 mm and never observed around DEM-BLAND. Drug concentration was above the therapeutic level of 1.0 µM up to a distance of 1.4 mm from the DEM to the tumor. Laparoscopic subperitoneal injection of chemo-loaded particles is feasible and lowers tumor growth and viability in a rabbit model of peritoneal carcinomatosis after 1 week.

摘要

我们研究的目的是评估控释化疗对兔VX2模型中经腹膜下注射治疗的腹膜癌生长和生存能力的影响。通过腹腔镜在12只白色新西兰兔的左右阔韧带中注射VX2肿瘤,建立腹膜癌模型。在第12天,每个肿瘤随机接受瘤周注射0.5 mL载有多柔比星的微球(DEM-DOX)或未载药微球(DEM-BLAND)。治疗7天后,测量肿瘤体积、组织学上的肿瘤生存能力、与DEM接触的局部肿瘤坏死情况以及药物洗脱微球(DEM)周围的多柔比星浓度分布。与DEM-BLAND组(8.9±5.4 cm)相比,DEM-DOX组的肿瘤体积显著更小(3.6±3.2 cm)(p = 0.0425)。与DEM-BLAND组(56%±20%)相比,DEM-DOX组的存活肿瘤组织百分比显著更低(38%±17%)(p = 0.0202)。在所有DEM-DOX周围均观察到组织坏死,坏死范围达1.094±0.852 mm,而在DEM-BLAND周围从未观察到组织坏死。从DEM到肿瘤的距离在1.4 mm范围内,药物浓度高于治疗水平1.0 μM。在兔腹膜癌模型中,腹腔镜腹膜下注射载化疗药物的微粒是可行的,并且在1周后可降低肿瘤生长和生存能力。

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