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Abstracts from the 2024 Veterinary Cancer Society (VCS) Annual Conference, 17-19 October 2024. 2024年兽医癌症协会(VCS)年会摘要,2024年10月17-19日。
IF 2.3 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-12-01 DOI: 10.1111/vco.13028
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引用次数: 0
Blood Neutrophil-to-Lymphocyte Ratio as a Potential Prognostic Marker in Dogs ≤10 kg With Multicentric Lymphoma. 血液中的中性粒细胞与淋巴细胞比值是≤10 千克多中心淋巴瘤患犬的潜在预后标志。
IF 2.3 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-12-01 Epub Date: 2024-08-01 DOI: 10.1111/vco.12992
SoYoung Park, Sehoon Kim, Yeon-Jung Hong, Jung-Hoon Park, Mangil Han, Younghee Lee, Min-Ok Ryu, Hwa-Young Youn, KyoungWon Seo

Canine lymphoma, the most prevalent haematopoietic tumour in dogs, presents significant challenges in veterinary oncology. This study investigates the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in small-sized dogs (≤10 kg) with multicentric lymphoma. In this retrospective study, we examined medical records and haematological data from 35 dogs to assess the association between NLR and two key outcomes: time-to-progression (TTP) and lymphoma-specific survival (LSS) using Cox proportional hazards models. Our findings revealed a significant correlation between elevated NLR and a worse prognosis, as evidenced by TTP (p = 0.005) and LSS (p = 0.001). NLR is linked to increased hazard ratios (HRs) for the time-to-progression rate (TTPR) at 180, 360 and 540 days (p = 0.001, p = 0.003 and p = 0.005, respectively) and the lymphoma-specific survival rate (LSSR) at the same intervals (p = 0.016, p = 0.001 and p = 0.001, respectively). Cutoff value of 3.764 for NLR was established, above which there is a significantly increased risk of early disease progression and decreased survival. Additionally, our analysis indicates that dogs with substage b exhibited earlier progression than those with substage a, evident in overall (p = 0.026) and TTPR at 180 days (p = 0.004), 360 days (p = 0.018), 540 days (p = 0.026) and LSSR at 180 days (p = 0.033). The results underscore the potential of NLR as a prognostic marker in cases of dogs ≤10 kg with multicentric lymphoma, suggesting that higher NLR is associated with a poorer prognosis.

犬淋巴瘤是犬中最常见的造血肿瘤,给兽医肿瘤学带来了巨大挑战。本研究探讨了中性粒细胞与淋巴细胞比值(NLR)在患有多中心淋巴瘤的小型犬(体重≤10 千克)中的预后价值。在这项回顾性研究中,我们检查了 35 只犬的病历和血液学数据,并使用 Cox 比例危险模型评估了 NLR 与两个关键结果之间的关系:进展时间(TTP)和淋巴瘤特异性生存率(LSS)。我们的研究结果表明,NLR 升高与预后恶化之间存在明显的相关性,TTP(p = 0.005)和 LSS(p = 0.001)证明了这一点。NLR与180天、360天和540天的进展时间率(TTPR)(分别为p = 0.001、p = 0.003和p = 0.005)和相同时间间隔的淋巴瘤特异性生存率(LSSR)(分别为p = 0.016、p = 0.001和p = 0.001)的危险比(HRs)增加有关。NLR 的临界值为 3.764,超过这一临界值,疾病早期恶化和存活率下降的风险会显著增加。此外,我们的分析表明,与亚阶段 a 的犬相比,亚阶段 b 的犬表现出更早的病情进展,这在总体(p = 0.026)、180 天时的 TTPR(p = 0.004)、360 天时的 TTPR(p = 0.018)、540 天时的 TTPR(p = 0.026)和 180 天时的 LSSR(p = 0.033)方面都很明显。这些结果表明,在体重≤10 千克的犬患多中心淋巴瘤的病例中,NLR 有可能是一种预后标志物,表明较高的 NLR 与较差的预后有关。
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引用次数: 0
Hotspot Exon 15 Mutations in BRAF Are Uncommon in Feline Tumours. BRAF 第 15 号外显子热点突变在猫科动物肿瘤中并不常见。
IF 2.3 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-09-01 Epub Date: 2024-07-17 DOI: 10.1111/vco.12997
Kei Kuroki, Christine Tran Hoang, Anita M Rogic, Hans Rindt, Angelynn Simenson, Lucie G Noall, Jeffrey N Bryan, Gayle C Johnson, Shirley Chu

BRAF is one of multiple RAF proteins responsible for the activation of the MAPK cell signalling cascade involved in cell growth, differentiation, and survival. A hotspot BRAFV600E mutation, in exon 15, was determined to be a driver in 100% hairy cell leukaemias, 50%-60% of human melanomas, 30%-50% of human thyroid carcinomas and 10%-20% of human colorectal carcinomas. The orthologous BRAFV595E mutation was seen in 67% and 80% of canine bladder transitional cell carcinomas and prostatic adenocarcinomas, respectively. Since veterinary and human cancers exploit similar pathways and BRAF is highly conserved across species, BRAF can be expected to be a driver in a feline cancer. Primers were developed to amplify exon 15 of feline BRAF. One hundred ninety-six feline tumours were analysed. Sanger sequencing of the 211 bp PCR amplicon was done. A BRAF mutation was found in one tumour, a cutaneous melanoma. The mutation was a BRAFV597E mutation, orthologous to the canine and human hotspot mutations. A common synonymous variant, BRAFT586T, was seen in 23% (47/196) of tumours. This variant was suspected to be a single nucleotide polymorphism. BRAF was not frequently mutated in common feline tumours or in tumour types that frequently harbour BRAF mutations in human and canine cancers. As is seen in canine cancer genomics, the mutational profile in feline tumours may not parallel the histologic equivalent in human oncology.

BRAF 是多种 RAF 蛋白之一,负责激活 MAPK 细胞信号级联,参与细胞生长、分化和存活。第 15 号外显子中的热点 BRAFV600E 突变被确定为 100%毛细胞白血病、50%-60% 人类黑色素瘤、30%-50% 人类甲状腺癌和 10%-20% 人类结直肠癌的驱动因素。在犬膀胱过渡细胞癌和前列腺腺癌中,分别有 67% 和 80% 出现了同源的 BRAFV595E 突变。由于兽类和人类癌症利用类似的途径,而且 BRAF 在不同物种间高度保守,因此 BRAF 可能是猫科动物癌症的驱动因素。我们开发了扩增猫科动物 BRAF 第 15 外显子的引物。对 196 例猫科动物肿瘤进行了分析。对 211 bp PCR 扩增片段进行了 Sanger 测序。在一个皮肤黑色素瘤中发现了 BRAF 突变。该突变为 BRAFV597E 突变,与犬和人类的热点突变同源。23%(47/196)的肿瘤中出现了常见的同义变异 BRAFT586T。该变异被怀疑是单核苷酸多态性。在常见的猫科动物肿瘤中,或在人类和犬科动物癌症中经常出现 BRAF 突变的肿瘤类型中,BRAF 突变并不常见。正如犬类癌症基因组学所显示的那样,猫科动物肿瘤的突变情况可能与人类肿瘤学的组织学特征不尽相同。
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引用次数: 0
Identification of hypoxia-induced metabolism-associated genes in canine tumours. 犬肿瘤中缺氧诱导代谢相关基因的鉴定。
IF 2.3 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-09-01 Epub Date: 2024-05-07 DOI: 10.1111/vco.12979
Taiki Kato, Masashi Sakurai, Kenji Watanabe, Yoichi Mizukami, Takayuki Nakagawa, Kenji Baba, Takuya Mizuno, Masaya Igase

Canine tumours including urothelial carcinoma, lung adenocarcinoma, mammary gland tumour, squamous cell carcinoma, and melanoma have been identified as causes of death, but effective therapies are limited due to insufficient knowledge of the molecular mechanisms involved. Within the tumour microenvironment, hypoxia activates hypoxia-inducible factor 1α (HIF1α) in tumour cells. High HIF1α expression correlates with enhanced glycolysis and poorer outcomes in human cancers. However, the molecular mechanisms underlying hypoxic tumour cells remain elusive in dogs. In our study, we investigated upregulated genes in a canine malignant melanoma cell line during hypoxia using RNA-sequencing analysis. Glycolysis and HIF1 signalling pathways were upregulated in hypoxic melanoma cells. HIF1α knockout melanoma cells revealed that the glycolysis marker MCT4 is regulated by HIF1α activation. Hypoxia induces high lactate secretion due to enhanced glycolysis in canine melanoma cells. Furthermore, we examined monocarboxylate transporter 4 (MCT4) expression in malignant melanoma and eight other types of canine tumour tissues using immunohistochemistry (IHC). Membrane-localized MCT4 protein was mostly detected in urothelial carcinoma and lung adenocarcinoma rather than malignant melanoma. We conclude that canine MCT4 protein plays a role in lactic acid efflux from glycolytic cells and may serve as a marker for hypoxia and glycolysis in canine tumours. These findings could inform future therapeutic strategies targeting MCT4.

包括尿道癌、肺腺癌、乳腺肿瘤、鳞状细胞癌和黑色素瘤在内的犬肿瘤已被确定为死亡原因,但由于对其中涉及的分子机制了解不足,有效的疗法受到限制。在肿瘤微环境中,缺氧会激活肿瘤细胞中的缺氧诱导因子 1α(HIF1α)。HIF1α 的高表达与糖酵解增强和人类癌症的不良预后有关。然而,狗体内肿瘤细胞缺氧的分子机制仍然难以捉摸。在我们的研究中,我们利用 RNA 序列分析研究了犬恶性黑色素瘤细胞系在缺氧过程中的上调基因。缺氧黑色素瘤细胞中糖酵解和 HIF1 信号通路上调。HIF1α基因敲除黑色素瘤细胞显示,糖酵解标志物MCT4受HIF1α激活的调节。在犬黑色素瘤细胞中,由于糖酵解增强,缺氧会诱导高乳酸分泌。此外,我们还利用免疫组化(IHC)技术检测了单羧酸盐转运体4(MCT4)在恶性黑色素瘤和其他八种犬肿瘤组织中的表达。膜定位的 MCT4 蛋白主要在尿路上皮癌和肺腺癌中检测到,而不是在恶性黑色素瘤中。我们的结论是,犬 MCT4 蛋白在糖酵解细胞的乳酸外流中发挥作用,可作为犬肿瘤缺氧和糖酵解的标记物。这些发现可为未来针对 MCT4 的治疗策略提供依据。
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引用次数: 0
DNA Methylation and Its Effects on TRIM29 Gene Expression in the Equine Sarcoid Tissue. 马肉瘤组织中的 DNA 甲基化及其对 TRIM29 基因表达的影响
IF 2.3 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-09-01 Epub Date: 2024-07-10 DOI: 10.1111/vco.12994
Semik-Gurgul Ewelina, Zaborowska Anna, Pędziwiatr Rafał, Witkowski Maciej

Sarcoids are the most frequently diagnosed dermatological tumour in horses. It is a disease that can affect various species of equids, such as donkeys, mules and zebras. This type of tumour can develop in all horse breeds, regardless of age and gender. Treatment options depend on many factors, such as the type of lesion, location, extent, owner preference and financial considerations. In the present study, we investigated the TRIM29 expression, the methylation status of its first exon and its involvement in the formation of equine sarcoids. Bisulfite sequencing PCR (BSP) was used to determine DNA methylation at CpG sites and real-time quantitative polymerase chain reaction (qPCR) was used to detect TRIM29 expression level. Our results showed that TRIM29 is significantly downregulated in lesional samples (FC = -3.72; p < 0.001). Furthermore, TRIM29 expression was significantly correlated (R = -0.73; p < 0.001) with hypermethylation of its specific CpG sites in the first exon of this gene. Our research has demonstrated that the identification of increased methylation of CpG sequences in horse sarcoids, along with the decreased expression of the TRIM29 gene, is an important step towards understanding the molecular mechanisms underlying the disease. These findings can serve in the future as a diagnostic biomarker for horse sarcoids and help in detecting the disease.

肉瘤是马最常见的皮肤肿瘤。驴、骡和斑马等不同种类的马都可能患上这种疾病。无论年龄和性别,所有品种的马都可能患上这种肿瘤。治疗方案取决于多种因素,如病变类型、位置、范围、马主偏好和经济考虑。在本研究中,我们调查了 TRIM29 的表达、其第一个外显子的甲基化状态及其与马肉瘤形成的关系。亚硫酸氢盐测序 PCR(BSP)用于确定 CpG 位点的 DNA 甲基化,实时定量聚合酶链反应(qPCR)用于检测 TRIM29 的表达水平。结果显示,TRIM29在病变样本中明显下调(FC = -3.72; p
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引用次数: 0
Molecular and Pathobiology of Canine Mammary Tumour: Defining a Translational Model for Human Breast Cancer. 犬乳腺肿瘤的分子和病理生物学:确定人类乳腺癌的转化模型。
IF 2.3 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-09-01 Epub Date: 2024-07-16 DOI: 10.1111/vco.12996
Adália F Oliveira-Lopes, Marcelo M Götze, Belarmino E Lopes-Neto, Denise D Guerreiro, Ivan Cunha Bustamante-Filho, Arlindo Alencar Moura

Canine mammary tumours (CMT) have histological, clinicopathological and molecular resemblances to human breast cancer (HBC), positioning them as viable models for studying the human disease. CMT initiation and progression occur spontaneously in immune-competent animals, which challenge the suggested limitations of genetically modified mice, also enabling the evaluation of immunotherapies in canine patients. Dogs have shorter life expectancy compared to humans, and cancer advances more rapidly in this species. This makes it possible to perform studies about the clinical efficacy of new therapeutic modalities in a much shorter time than in human patients. The identification of biomarkers for tumour subtypes, progression and treatment response paves the way for the development of novel therapeutic and diagnostic approaches. This review addresses the similarities between CMT and HBC and the molecular signatures identified in CMT samples that have been explored to date. We proposed a detailed molecular exploration of the CMT stroma using state-of-the-art methods in transcriptomics and proteomics. Using CMT as an analog for HBC not only helps to understand the complexities of the disease, but also to advance comparative oncology to the next level to prove the claim of dogs as a valid translational model.

犬乳腺肿瘤(CMT)在组织学、临床病理学和分子学方面与人类乳腺癌(HBC)相似,因此可作为研究人类疾病的可行模型。乳腺肿瘤的发生和发展是在免疫功能正常的动物体内自发进行的,这对转基因小鼠的局限性提出了挑战,同时也有利于对犬病患者的免疫疗法进行评估。与人类相比,狗的预期寿命较短,癌症在这一物种中发展得更快。因此,可以在比人类患者短得多的时间内对新治疗方法的临床疗效进行研究。确定肿瘤亚型、进展和治疗反应的生物标志物为开发新型治疗和诊断方法铺平了道路。本综述探讨了 CMT 和 HBC 之间的相似性,以及迄今为止在 CMT 样本中发现的分子特征。我们建议使用最先进的转录组学和蛋白质组学方法对 CMT 基质进行详细的分子探索。将 CMT 作为 HBC 的类似物不仅有助于了解该疾病的复杂性,还能将比较肿瘤学推向新的高度,证明狗是一种有效的转化模型。
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引用次数: 0
Use of Lomustine and Prednisolone as First-Line Treatment in Canine Multicentric Lymphoma. 将洛莫司汀和泼尼松龙作为犬多中心淋巴瘤的一线治疗药物
IF 2.3 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-09-01 Epub Date: 2024-06-18 DOI: 10.1111/vco.12990
Chiara Catalucci, Marco Luigi Bianchi, Elisabetta Treggiari, Marta Pieri, Katja Ruess, Paola Valenti

Multiagent chemotherapy is considered the most effective treatment for canine high-grade lymphoma; however, due to cost and time requirements, single-agent protocols have also been described. The aim of our study was to evaluate the outcome and prognostic factors of dogs affected by multicentric lymphoma treated with lomustine and prednisolone as first-line treatment. Cases of medium-large-cell multicentric lymphoma treated with lomustine and prednisolone were included in the study. Response to therapy, time to progression (TTP), median disease-free interval (MDFI) and median survival time (MST) were retrospectively described. Thirty cases were included. Eleven (36.67%) were T cell, 11 (36.67%) were B cell and 8 (26.66%) had unknown immunophenotype. The overall response rate (RR) was 87%, with 15 patients achieving CR (50%) and 11 patients PR (37%). The median TTP, MDFI and MST were 42, 63 and 90 days, respectively. The only factor significantly associated with MDFI and MST was the stage. Dogs with multicentric lymphoma treated with lomustine and prednisolone have lower RR, TTP, MDFI and MST compared with dogs receiving multiagent protocols. Based on the short-lasting response, this study confirms that this protocol might have minimal utility beyond palliation.

多药化疗被认为是犬高级淋巴瘤最有效的治疗方法;然而,由于成本和时间要求,也有描述单药方案的。我们的研究旨在评估以洛莫司汀和泼尼松龙作为一线疗法的多中心淋巴瘤患犬的疗效和预后因素。研究对象包括接受洛莫司汀和泼尼松龙治疗的中大细胞多中心淋巴瘤病例。对治疗反应、进展时间(TTP)、中位无病间隔时间(MDFI)和中位生存时间(MST)进行了回顾性描述。研究共纳入 30 个病例。11例(36.67%)为T细胞,11例(36.67%)为B细胞,8例(26.66%)免疫表型不明。总反应率(RR)为87%,其中15名患者达到CR(50%),11名患者达到PR(37%)。中位TTP、MDFI和MST分别为42天、63天和90天。与MDFI和MST明显相关的唯一因素是分期。与接受多药方案治疗的犬相比,接受洛莫司汀和泼尼松龙治疗的多中心淋巴瘤犬的RR、TTP、MDFI和MST均较低。由于反应持续时间较短,本研究证实该方案除了缓解病情外,可能作用甚微。
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引用次数: 0
Immunohistochemical and transcriptomic characterization of T and myeloid cell infiltrates in canine malignant melanoma. 犬恶性黑色素瘤中 T 细胞和骨髓细胞浸润的免疫组织化学和转录组学特征。
IF 2.3 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-09-01 Epub Date: 2024-05-16 DOI: 10.1111/vco.12981
Kathryn E Cronise, Jonathan Coy, Steven Dow, Marlene L Hauck, Daniel P Regan

Immune checkpoint inhibitor therapy can provide significant clinical benefit in patients with certain cancer types including melanoma; however, objective responses are only observed for a subset of patients. Mucosal melanoma is a rare melanoma subtype associated with a poor prognosis and, compared with cutaneous melanoma, is significantly less responsive to immune checkpoint inhibitors. Spontaneous canine tumours have emerged as valuable models to inform human cancer studies. In contrast to human melanoma, most canine melanomas are mucosal-an incidence that may be leveraged to better understand the subtype in humans. However, a more comprehensive understanding of the immune landscape of the canine disease is required. Here, we quantify tumour infiltrative T and myeloid cells in canine mucosal (n = 13) and cutaneous (n = 5) melanomas using immunohistochemical analysis of CD3 and MAC387 expression, respectively. Gene expression analysis using the Canine IO NanoString panel was also performed to identify genes and pathways associated with immune cell infiltration. T and myeloid cell densities were variable with geometric means of 158.7 cells/mm2 and 166.7 cells/mm2, respectively. Elevated T cell infiltration was associated with increased expression of cytolytic genes as well as genes encoding the coinhibitory checkpoint molecules PD-1, CTLA-4, TIM-3 and TIGIT; whereas increased myeloid cell infiltration was associated with elevated expression of protumourigenic cytokines. These data provide a basic characterization of the tumour microenvironment of canine malignant melanoma and suggest that, like human melanoma, inherent variability in anti-tumour T cell responses exists and that a subset of canine melanomas may respond better to immunomodulation.

免疫检查点抑制剂疗法可为包括黑色素瘤在内的某些癌症类型患者带来显著的临床获益;然而,只有一部分患者能观察到客观反应。粘膜黑色素瘤是一种罕见的黑色素瘤亚型,预后较差,与皮肤黑色素瘤相比,对免疫检查点抑制剂的反应明显较弱。自发性犬肿瘤已成为人类癌症研究的重要参考模型。与人类黑色素瘤不同的是,犬黑色素瘤大多为粘膜瘤--这种发病率可用于更好地了解人类黑色素瘤的亚型。然而,我们需要更全面地了解犬类疾病的免疫状况。在这里,我们分别使用 CD3 和 MAC387 表达的免疫组化分析方法对犬粘膜(13 例)和皮肤(5 例)黑色素瘤中的肿瘤浸润性 T 细胞和髓细胞进行了量化。还使用犬 IO NanoString 面板进行了基因表达分析,以确定与免疫细胞浸润相关的基因和通路。T 细胞和骨髓细胞密度各不相同,几何平均数分别为 158.7 个细胞/mm2 和 166.7 个细胞/mm2。T细胞浸润的增加与细胞溶解基因以及共同抑制检查点分子PD-1、CTLA-4、TIM-3和TIGIT的编码基因的表达增加有关;而髓样细胞浸润的增加与原发肿瘤细胞因子的表达增加有关。这些数据提供了犬恶性黑色素瘤肿瘤微环境的基本特征,并表明与人类黑色素瘤一样,抗肿瘤 T 细胞反应也存在固有的变异性,而且犬黑色素瘤亚群可能对免疫调节反应更好。
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引用次数: 0
Distribution of Inflammatory Infiltrate in Feline Mammary Lesions: Relationship With Clinicopathological Features. 猫科动物乳腺病变中炎性浸润的分布:与临床病理特征的关系
IF 2.3 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-09-01 Epub Date: 2024-06-11 DOI: 10.1111/vco.12987
Joana Rodrigues-Jesus, Ana Canadas-Sousa, Pedro Oliveira, Ana Catarina Figueira, Carla Marrinhas, Gonçalo N Petrucci, Hugo Gregório, Flora Tinoco, Andrea Goulart, Helena Felga, Hugo Vilhena, Patrícia Dias-Pereira

Inflammation is a frequent finding in feline mammary neoplasms. Recent research suggests that the presence and location of tumour-associated immune cells might play a significant role in the clinical outcome of feline mammary carcinomas. The present study aimed to characterise the overall inflammatory infiltrates in healthy, hyperplastic/dysplastic, benign and malignant lesions of the feline mammary gland, and to evaluate its association with clinicopathological features. Perilesional and intralesional inflammatory foci were evaluated in 307 lesions from 185 queens, and categorised according to its distribution and intensity. The presence, location and density of tertiary lymphoid structures were also assessed. A control group included 24 queens without mammary changes. The presence of intralesional and perilesional inflammatory infiltrate was observed in a majority of the lesions (80.8% and 90.2%, respectively), but differed according to the type of mammary lesion, being more remarkable in malignant neoplasms. Only scarce individual cells were observed in 28.1% of the normal mammary glands. Data analysis revealed statistically significant associations (p < 0.05) between the presence of a more prominent intralesional and perilesional inflammatory reaction and several clinicopathological features associated with worse prognosis, including clinical stage, tumour size, mitotic count, lymphovascular invasion and lymph node metastasis. Furthermore, tertiary lymphoid structures were significantly more frequent in tumours with an infiltrative growth and lymph node metastasis. According to our results, the inflammatory reaction present in different types of feline mammary lesions is associated with the development of more aggressive tumours.

炎症是猫科动物乳腺肿瘤的常见症状。最近的研究表明,肿瘤相关免疫细胞的存在和位置可能对猫乳腺癌的临床结果起着重要作用。本研究旨在描述猫乳腺健康、增生/发育不良、良性和恶性病变中整体炎症浸润的特征,并评估其与临床病理特征的关联。对来自 185 只猫科动物的 307 个病灶的周围和内部炎症病灶进行了评估,并根据其分布和强度进行了分类。此外,还评估了三级淋巴结构的存在、位置和密度。对照组包括 24 只没有乳腺病变的皇后。在大多数病变(分别为 80.8% 和 90.2%)中都观察到了乳腺内部和周围的炎症浸润,但根据乳腺病变的类型而有所不同,恶性肿瘤中的炎症浸润更为明显。在 28.1%的正常乳腺中仅观察到稀少的单个细胞。数据分析显示,在统计意义上(p
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引用次数: 0
Pilot study to evaluate isolation by size of circulating tumour cells in canine oral melanoma. 评估犬口腔黑色素瘤循环肿瘤细胞大小分离的试点研究。
IF 2.3 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2024-09-01 Epub Date: 2024-06-04 DOI: 10.1111/vco.12982
Victor Nowosh, Alexcia Camila Braun, Anna Paula Carreta Ruano, Ludmilla Thomé Domingos Chinén, Cristina de Oliveira Massoco

Liquid biopsy for circulating tumour cell (CTC) detection is generally unexplored in veterinary medicine. Dogs with highly aggressive and heterogeneous tumours, such as oral malignant melanoma (OMM), could benefit from studies involving size-based isolation methods for CTCs, as they do not depend on specific antibodies. This pilot study aimed to detect CTCs from canine OMM using Isolation by Size of Epithelial Tumor Cells (ISET), a microfiltration methodology, followed by immunocytochemistry (ICC) with Melan-A, PNL2, and S100 antibodies. Ten canine patients diagnosed by histopathology and confirmed as OMM by immunohistochemistry were enrolled, their prognostic data was assessed, and blood samples were collected for CTC analysis. Results have shown the detection of intact cells in 9/10 patients. ICC has shown 3/9 Melan-A-positive, 3/9 PNL2-positive, and 8/9 S100-positive patients, confirming the importance of opting for a multimarker assay. A significant number of negative-stained CTCs were found, suggesting their high heterogeneity in circulation. Microemboli stained with either PNL2 or S100 were found in a patient with a high isolated cell count and advanced clinical stage. Preliminary statistical analysis shows a significant difference in CTC count between patients with and without lymph node metastasis (p < .05), which may correlate with tumour metastatic potential. However, we recommend further studies with more extensive sampling to confirm this result. This pilot study is the first report of intact CTC detection in canine OMM and the first application of ISET in veterinary medicine, opening new possibilities for liquid biopsy studies in canine OMM and other tumours.

在兽医领域,用于循环肿瘤细胞(CTC)检测的液体活检技术通常还未得到开发。口腔恶性黑色素瘤(OMM)等具有高度侵袭性和异质性肿瘤的狗可以从基于大小的 CTC 分离方法研究中获益,因为这种方法不依赖于特异性抗体。这项试验性研究的目的是利用微滤方法 "上皮肿瘤细胞大小分离"(ISET)检测犬口腔恶性黑色素瘤的 CTC,然后用 Melan-A、PNL2 和 S100 抗体进行免疫细胞化学分析(ICC)。十名经组织病理学诊断并通过免疫组化确诊为 OMM 的犬类患者被纳入研究,他们的预后数据得到了评估,并被采集血液样本用于 CTC 分析。结果显示,9/10 的患者检测到了完整的细胞。ICC显示3/9的患者Melan-A阳性,3/9的患者PNL2阳性,8/9的患者S100阳性,这证实了选择多标记检测的重要性。发现了大量阴性染色的 CTC,这表明它们在血液循环中具有高度异质性。在一名孤立细胞数量较多且处于临床晚期的患者身上,发现了被 PNL2 或 S100 染色的微栓子。初步统计分析表明,有淋巴结转移和没有淋巴结转移的患者之间的 CTC 数量存在显著差异(p
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引用次数: 0
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Veterinary and comparative oncology
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