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在雌性 CB17 SCID 小鼠的卵巢癌原位肿瘤模型中,丁丙诺啡的作用。

Effects of Buprenorphine in a Preclinical Orthotopic Tumor Model of Ovarian Carcinoma in Female CB17 SCID Mice.

机构信息

Office of Animal Welfare, AbbVie, North Chicago, Illinois; Development Sciences, AbbVie, North Chicago, Illinois;, Email:

Oncology In Vivo Biology, AbbVie, North Chicago, Illinois; Drug Discovery, AbbVie, North Chicago, Illinois.

出版信息

J Am Assoc Lab Anim Sci. 2019 Sep 1;58(5):583-588. doi: 10.30802/AALAS-JAALAS-18-000127. Epub 2019 Aug 14.

DOI:10.30802/AALAS-JAALAS-18-000127
PMID:31412976
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6774455/
Abstract

In the development of cancer therapeutics, no suitable replacements for the use of animals that are capable of modeling such complex disease processes are currently available. In orthotopic models, surgery is often required to access the target organ for tumor cell inoculation. Historically analgesics have been withheld in such models in light of potential effects on tumor development. The current study evaluated the effect of the opioid buprenorphine on tumor growth of a human ovarian cancer cell line (OVCAR5 OT luc2 mCherry). Female CB17 SCID mice ( = 150) underwent surgery for orthotopic inoculation and were assigned to 1 of 3 treatment groups: vehicle control, 1 dose of buprenorphine, or 2 doses of buprenorphine administered perioperatively. Bioluminescence imaging revealed no significant difference on tumor engraftment rate or growth between control and analgesia-treated groups. These data demonstrate that acute, perioperative analgesia with buprenorphine did not alter tumor growth. Although further research is needed to evaluate potential effects of buprenorphine in other cell lines and mouse strains, the justification for withholding analgesia and the potential influence of pain and stress due to insufficient analgesia in these models should be considered thoroughly.

摘要

在癌症治疗的发展过程中,目前还没有合适的替代品来替代能够模拟这种复杂疾病过程的动物。在原位模型中,通常需要手术才能进入目标器官进行肿瘤细胞接种。由于担心对肿瘤发展有潜在影响,历史上在这些模型中一直不使用镇痛药。本研究评估了阿片类药物丁丙诺啡对人卵巢癌细胞系(OVCAR5 OT luc2 mCherry)生长的影响。雌性 CB17 SCID 小鼠(n=150)接受了原位接种手术,并被分配到 3 个治疗组中的 1 个:载体对照组、1 剂量丁丙诺啡组或围手术期给予 2 剂量丁丙诺啡组。生物发光成像显示,对照组和镇痛治疗组之间在肿瘤植入率或生长方面没有显著差异。这些数据表明,丁丙诺啡的急性围手术期镇痛不会改变肿瘤生长。尽管需要进一步研究来评估丁丙诺啡在其他细胞系和小鼠品系中的潜在作用,但应仔细考虑在这些模型中因不充分镇痛而保留镇痛和潜在的疼痛和应激影响的合理性。

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本文引用的文献

1
Analgesics promote welfare and sustain tumour growth in orthotopic 4T1 and B16 mouse cancer models.在原位4T1和B16小鼠癌症模型中,镇痛药可促进机体健康并维持肿瘤生长。
Lab Anim. 2018 Aug;52(4):351-364. doi: 10.1177/0023677217739934. Epub 2017 Dec 5.
2
Quantification of Induced Hypothermia from Aseptic Scrub Applications during Rodent Surgery Preparation.啮齿动物手术准备期间无菌擦洗应用导致的体温过低的量化。
J Am Assoc Lab Anim Sci. 2017 Sep 1;56(5):562-569.
3
Clearance of systemic hematologic tumors by venetoclax (Abt-199) and navitoclax.依鲁替尼(Abt-199)和 navitoclax 清除全身血液系统肿瘤。
Pharmacol Res Perspect. 2015 Oct;3(5):e00178. doi: 10.1002/prp2.178. Epub 2015 Sep 1.
4
Surgery as a double-edged sword: a clinically feasible approach to overcome the metastasis-promoting effects of surgery by blunting stress and prostaglandin responses.手术犹如双刃剑:一种可行的临床方法,通过钝化应激和前列腺素反应来克服手术促进转移的作用。
Cancers (Basel). 2010 Nov 24;2(4):1929-51. doi: 10.3390/cancers2041929.
5
Can anaesthetic and analgesic techniques affect cancer recurrence or metastasis?麻醉和镇痛技术会影响癌症的复发或转移吗?
Br J Anaesth. 2012 Dec;109 Suppl 1:i17-i28. doi: 10.1093/bja/aes421.
6
Using the Mouse Grimace Scale to reevaluate the efficacy of postoperative analgesics in laboratory mice.使用小鼠面部表情评分法重新评估实验小鼠术后镇痛药的疗效。
J Am Assoc Lab Anim Sci. 2012 Jan;51(1):42-9.
7
Morphine and tumor growth and metastasis.吗啡与肿瘤生长和转移。
Cancer Metastasis Rev. 2011 Jun;30(2):225-38. doi: 10.1007/s10555-011-9285-0.
8
The novel role of the mu opioid receptor in lung cancer progression: a laboratory investigation.μ 阿片受体在肺癌进展中的新作用:一项实验室研究。
Anesth Analg. 2011 Mar;112(3):558-67. doi: 10.1213/ANE.0b013e31820568af. Epub 2010 Dec 14.
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Burrowing behavior as an indicator of post-laparotomy pain in mice.打洞行为作为小鼠剖腹术后疼痛的一个指标。
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Effect of anaesthetic technique and other perioperative factors on cancer recurrence.麻醉技术及其他围手术期因素对癌症复发的影响。
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