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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。

Analgesics promote welfare and sustain tumour growth in orthotopic 4T1 and B16 mouse cancer models.

作者信息

Lofgren Jennifer, Miller Amy L, Lee Claudia Chui Shan, Bradshaw Carla, Flecknell Paul, Roughan Johnny

机构信息

1 Unit for Laboratory Animal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.

2 School of Agriculture, Food and Rural Development, Newcastle University, Newcastle upon Tyne, UK.

出版信息

Lab Anim. 2018 Aug;52(4):351-364. doi: 10.1177/0023677217739934. Epub 2017 Dec 5.

Abstract

Murine orthotopic cancer models often require surgery, potentially causing pain or distress. However, analgesics are often withheld because they may alter tumour development. Two orthotopically implanted cancers were investigated in mice pre-treated with meloxicam (10 mg/kg), buprenorphine (0.2 mg/kg) or saline (1 ml/kg). Tumours were imaged and welfare was assessed using body weight, behaviour and nociceptive responses. In study 1, BALB/c mice were inoculated with 4T1 mammary carcinoma or saline during surgery or anaesthesia. As pre-treatment with a single buprenorphine dose appeared beneficial to cancer growth consistency, a second cohort of mice additionally received saline or buprenorphine at 12 and 24 h. Surgery resulted in increased mammary tumour growth and lung metastases. These unwanted effects were lessened by buprenorphine pre-treatment, especially when given repeatedly. Mammary tumour-bearing mice became less active and nociceptive thresholds declined over time, indicating some discomfort as tumours grew. In study 2, C57BL/6 mice received B16 melanoma. This non-surgical model was used to determine whether meloxicam or buprenorphine affected cancer seeding of the lungs. While meloxicam reduced B16 lung seeding, buprenorphine did not. Mechanical thresholds decreased as cancer developed in mice bearing melanoma, but the magnitude of this was insufficient to conclude that there were any significant welfare concerns. This study highlights the scientific value in utilising non-surgical models, where possible. When surgery must be performed at the time of tumour inoculation, the effects of this should be controlled with appropriate analgesics to enhance the value and possibly translation of the research.

摘要

小鼠原位癌模型通常需要进行手术,这可能会导致疼痛或痛苦。然而,镇痛药往往不使用,因为它们可能会改变肿瘤的发展。对两组原位植入癌的小鼠进行了研究,这些小鼠预先接受了美洛昔康(10毫克/千克)、丁丙诺啡(0.2毫克/千克)或生理盐水(1毫升/千克)处理。对肿瘤进行成像,并通过体重、行为和伤害性反应评估动物健康状况。在研究1中,BALB/c小鼠在手术或麻醉期间接种4T1乳腺癌细胞或生理盐水。由于单次给予丁丙诺啡似乎有利于癌症生长的一致性,第二组小鼠在12小时和24小时时额外接受了生理盐水或丁丙诺啡。手术导致乳腺肿瘤生长增加和肺转移。丁丙诺啡预处理减轻了这些不良影响,尤其是重复给药时。随着肿瘤生长,荷乳腺肿瘤小鼠的活动减少,伤害性阈值下降,表明存在一些不适。在研究2中,C57BL/6小鼠接种了B16黑色素瘤。这个非手术模型用于确定美洛昔康或丁丙诺啡是否影响肺部的癌症播种。虽然美洛昔康减少了B16在肺部的播种,但丁丙诺啡没有。在荷黑色素瘤小鼠中,随着癌症发展,机械阈值降低,但降低幅度不足以得出存在任何重大动物健康问题的结论。这项研究强调了在可能的情况下使用非手术模型的科学价值。当在接种肿瘤时必须进行手术时,应使用适当的镇痛药来控制其影响,以提高研究的价值并可能促进研究成果的转化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/6068963/d1ff27d7161a/10.1177_0023677217739934-fig1.jpg

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