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创伤促进卵巢癌进展,并降低顺铂在同源小鼠模型中的疗效。

Wounding promotes ovarian cancer progression and decreases efficacy of cisplatin in a syngeneic mouse model.

机构信息

Division of Gynecologic Oncology, Princess Margaret Hospital Cancer Centre, Toronto, ON, Canada.

Lunenfeld-Tanenbaum Research Institute at Sinai Health Systems, Mt. Sinai Hospital, 60 Murray Street, 6-10016-3, Toronto, ON, M5T 3L9, Canada.

出版信息

J Ovarian Res. 2018 Jul 4;11(1):56. doi: 10.1186/s13048-018-0428-6.

DOI:10.1186/s13048-018-0428-6
PMID:29973223
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6032528/
Abstract

BACKGROUND

Primary cytoreductive surgery followed by adjuvant chemotherapy is the standard treatment for advanced epithelial ovarian cancer. The average interval between surgery and chemotherapy initiation is approximately 4-weeks at most centers; however, since surgery may accelerate residual tumor growth, a shorter interval may be more beneficial.

METHODS

The murine ID8 cell model of ovarian cancer was used to examine the efficacy of cisplatin treatment administered perioperatively or 7 days after surgical wounding. Luciferase-expressing cells ID8 cells were injected intraperitoneally (i.p.) into female C57/Bl6 mice. Fourteen days post-injection, animals received an abdominal incision or anesthesia alone and received i.p. cisplatin either on the surgical day or 7 days later, or received no chemotherapy. Additional animals received cisplatin 28 days after wounding for comparison.

RESULTS

Abdominal tumor mass increased 2.5-fold in wounded vs. unwounded animals as determined by bioluminescent in vivo tumor imaging. Cisplatin administered on the day of wounding decreased tumor burden by 50%, as compared to 90% in unwounded animals. Cisplatin on day 7 or day 28 decreased tumor burden by 80 and 37% respectively.

CONCLUSIONS

Surgical wounding increases ovarian tumor mass and decreases perioperative cisplatin efficacy in this animal model. Administration of cisplatin 1 week after surgery was more effective than cisplatin administered perioperatively or 4 weeks after surgery.

摘要

背景

初次细胞减灭术联合辅助化疗是治疗晚期上皮性卵巢癌的标准方法。大多数中心的手术和化疗起始之间的平均间隔时间约为 4 周;然而,由于手术可能加速残留肿瘤生长,因此较短的间隔时间可能更有益。

方法

使用小鼠 ID8 卵巢癌细胞模型来研究围手术期或手术后 7 天给予顺铂治疗的疗效。将表达荧光素酶的 ID8 细胞经腹腔内(i.p.)注射到雌性 C57/Bl6 小鼠中。注射后 14 天,动物接受腹部切口或单独麻醉,并在手术当天或 7 天后接受 i.p.顺铂治疗,或不接受化疗。其他动物在创伤后 28 天接受顺铂治疗以进行比较。

结果

通过体内肿瘤成像的生物发光确定,与未受伤的动物相比,受伤的动物腹部肿瘤质量增加了 2.5 倍。与未受伤的动物相比,在受伤当天给予顺铂可使肿瘤负担减少 50%,而在未受伤的动物中则减少 90%。在第 7 天或第 28 天给予顺铂可使肿瘤负担分别减少 80%和 37%。

结论

在该动物模型中,手术创伤会增加卵巢肿瘤的体积,并降低围手术期顺铂的疗效。手术后 1 周给予顺铂比围手术期或手术后 4 周给予顺铂更有效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/defb/6032528/edf687e40ac2/13048_2018_428_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/defb/6032528/3f65e3b5c5de/13048_2018_428_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/defb/6032528/01deb61dc087/13048_2018_428_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/defb/6032528/e8144cb6a930/13048_2018_428_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/defb/6032528/46a9794c77e5/13048_2018_428_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/defb/6032528/6de465aadcb9/13048_2018_428_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/defb/6032528/edf687e40ac2/13048_2018_428_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/defb/6032528/3f65e3b5c5de/13048_2018_428_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/defb/6032528/01deb61dc087/13048_2018_428_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/defb/6032528/e8144cb6a930/13048_2018_428_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/defb/6032528/46a9794c77e5/13048_2018_428_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/defb/6032528/6de465aadcb9/13048_2018_428_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/defb/6032528/edf687e40ac2/13048_2018_428_Fig6_HTML.jpg

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