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关于犬淋巴瘤模型在人类医学中已知与未知的内容——当前知识状况

英文原题:What We Know and Do Not Yet Know About the Canine Model of Lymphoma in Human Medicine-The Current State of Knowledge.

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What We Know and Do Not Yet Know About the Canine Model of Lymphoma in Human Medicine-The Current State of Knowledge.

PubMed 2025/02/10(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

这篇综述全面比较了人类和犬类淋巴瘤,强调犬类模型在转化研究中的实用性。犬淋巴瘤(cL)以弥漫性大B细胞淋巴瘤(DLBCL)为主,其临床表现与人类非霍奇金淋巴瘤(NHL)相似,包括淋巴结肿大、全身症状(如发热、体重减轻)和血液学异常。在形态学上,cL和NHL在DLBCL亚型(中心母细胞型、免疫母细胞型、间变性)方面具有相似性,尽管存在一些差异,例如犬多形性中心母细胞性淋巴瘤中存在巨核中等大小细胞,而人类中未观察到。犬和人类淋巴瘤共享分子机制,包括NF-κB和mTOR等关键通路的激活,以及遗传和表观遗传改变。肿瘤微环境在两种物种中均影响肿瘤生长和免疫逃逸。

两种物种对化疗(主要基于CHOP的方案)表现出相似的反应,尽管犬淋巴瘤通常进展更快,为更短的临床试验提供了优势。分子靶向治疗正成为一种有前景的治疗方法,人类疗法如rituximab和CAR-T 细胞疗法显示出疗效,而犬类治疗仍在发展中。流行病学数据揭示了重叠的风险因素,包括暴露于环境致癌物(如家用化学品、污染)以及性激素的潜在影响,尽管性激素在犬类中的作用需要进一步研究。虽然分期系统略有不同(人类采用Ann Arbor的Lugano修改版,犬采用WHO系统),但两者均考虑疾病范围和全身受累情况。预后因素,如乳酸脱氢酶(LDH)水平,在人类NHL中具有相关性,但在cL中尚未显示出一致的实用性。

本研究得出结论,在免疫功能正常的犬中自发性发生cL,加之其与人类NHL在临床、组织学和治疗方面的相似性,使该犬模型对于临床前研究具有不可估量的价值,可加速开发针对人类和犬淋巴瘤的新型诊断工具和疗法。共同的环境风险因素以及犬中更短的疾病进展进一步增强了该模型的转化潜力,促进了癌症研究的One Health方法。

展开英文摘要原文

This review comprehensively compares lymphoma in humans and dogs, highlighting the canine model's utility in translational research. Canine lymphoma (cL), predominantly diffuse large B-cell lymphoma (DLBCL), mirrors human non-Hodgkin's lymphoma (NHL) in its clinical presentation, including lymphadenopathy, systemic symptoms (e. g. , fever, weight loss), and hematological abnormalities. Morphologically, cL and NHL share similarities in DLBCL subtypes (centroblastic, immunoblastic, anaplastic), although some variations exist, such as the presence of macronuclear medium-sized cells in canine polymorphonuclear centroblastic lymphoma, not observed in humans. Canine and human lymphomas share molecular mechanisms, including the activation of key pathways like NF-κB and mTOR, and genetic and epigenetic alterations. The tumor microenvironment influences tumor growth and immune evasion in both species.

Both species exhibit similar responses to chemotherapy, primarily CHOP-based protocols, although canine lymphoma often progresses more rapidly, offering advantages for shorter clinical trials. Molecular targeted therapy is emerging as a promising treatment, with human therapies like rituximab and chimeric antigen receptor T-cell therapy showing efficacy, and canine treatments still developing. Epidemiological data reveal overlapping risk factors, including exposure to environmental carcinogens (e.

g. , household chemicals, pollution) and the potential influence of sex hormones, although the role of sex hormones requires further investigation in canines. While staging systems differ slightly (Lugano modification of Ann Arbor for humans, WHO system for dogs), both consider disease extent and systemic involvement. Prognostic factors, such as lactate dehydrogenase (LDH) levels, are relevant in human NHL but have not shown consistent utility in cL.

This study concludes that the spontaneous development of cL in immunocompetent dogs, coupled with its clinical, histological, and therapeutic similarities to human NHL, makes the canine model invaluable for preclinical research, accelerating the development of novel diagnostic tools and therapies for both human and canine lymphoma. The shared environmental risk factors and shorter disease progression in dogs further enhance the translational potential of this model, promoting a One Health approach to cancer research.

论文信息

作者
Będkowska D、Al-Ameri S、Wieczorek A、Bubak J、Miszczak M
第一作者单位
EZA Student Science Club, Department of Epizootiology and Clinic of Birds and Exotic Animals, Division of Infectious Diseases and Veterinary Administration, The Faculty of Veterinary Medicine, Wrocław University of Environmental and Life Sciences, Grunwaldzki Sq. 45, 50-366 Wrocław, Poland.Poland
通讯作者单位
Department of Epizootiology and Clinic of Birds and Exotic Animals, Division of Infectious Diseases and Veterinary Administration, The Faculty of Veterinary Medicine in Wroclaw, Wrocław University of Environmental and Life Sciences, Grunwaldzki Sq. 45, 50-366 Wrocław, Poland.Poland
文献类型
综述
期刊
Cancers2025 Feb 10
原文标识
PubMed 40002191 · DOI 10.3390/cancers17040596