Vicente Igor Simões Tiagua, de Moura Fernanda Barthelson Carvalho, Rozolen Juliana Moreira, Dos Anjos Denner Santos, Sobral Renata Afonso, Alves Carlos Eduardo Fonseca
Veterinarian, DSc., VetPrecision Laboratory, Botucatu, SP, Brazil.
Veterinarian, Departamento de Cirurgia Veterinária e Reprodução Animal, Escola de Medicina Veterinária e Zootecnia, Universidade Estadual de São Paulo (UNESP), Botucatu, SP, Brazil.
Braz J Vet Med. 2024 Aug 6;46:e001524. doi: 10.29374/2527-2179.bjvm001524. eCollection 2024.
Splenic tumors are very common in dogs, and canine hemangiosarcoma (HSA) is one of the most important malignant splenic tumors. Surgery followed by chemotherapy (anthracycline-based protocols) is recommended for treating canine HSA; however, patients still do not achieve long-term survival. Therefore, this research aimed to assess vascular endothelial growth factor receptor-2 () and platelet-derived growth factor receptor-β () gene expression in formalin-fixed tissues, evaluate the quality of mRNA for quantitative polymerase chain reaction (qPCR) analysis and identify drug repositioning candidates based on VEGFR-2 and PDGFR-β. qPCR analysis identified the relative expression of heterogeneous VEGFR-2 and PDGFR-β, with samples showing no transcripts or very low expression and those with higher relative quantification for both genes. We then used immunohistochemistry to correlate the relative quantification of VEGFR-2 and PDGFR-β transcripts with respective higher protein expression to validate our results. In the next step, we evaluated drug repositioning candidates and identified small molecule inhibitors (i.e. sorafenib) and natural compounds (curcumin and resveratrol) with the ability to block VEGFR-2 and PDGFR-β genes. Overall, our results indicated that VEGFR-2 and PDGFR-β expression is highly variable among canine HSA samples and different drugs can block the expression of both genes. Therefore, a personalized approach could be useful for selecting anti-VEGFR-2 and PDGFR-β therapies and both genes are potential candidates for future oncological panels.
脾脏肿瘤在犬类中非常常见，犬血管肉瘤（HSA）是最重要的恶性脾脏肿瘤之一。对于犬HSA的治疗，建议采用手术联合化疗（基于蒽环类药物的方案）；然而，患者仍无法实现长期存活。因此，本研究旨在评估福尔马林固定组织中血管内皮生长因子受体-2（）和血小板衍生生长因子受体-β（）基因的表达，评估用于定量聚合酶链反应（qPCR）分析的mRNA质量，并基于VEGFR-2和PDGFR-β确定药物重新定位的候选药物。qPCR分析确定了异质性VEGFR-2和PDGFR-β的相对表达，样本显示无转录本或表达极低，以及这两个基因相对定量较高的样本。然后，我们使用免疫组织化学将VEGFR-2和PDGFR-β转录本的相对定量与各自较高的蛋白表达相关联，以验证我们的结果。在下一步中，我们评估了药物重新定位的候选药物，并确定了具有阻断VEGFR-2和PDGFR-β基因能力的小分子抑制剂（即索拉非尼）和天然化合物（姜黄素和白藜芦醇）。总体而言，我们的结果表明，VEGFR-2和PDGFR-β在犬HSA样本中的表达高度可变，不同药物可阻断这两个基因的表达。因此，个性化方法可能有助于选择抗VEGFR-2和PDGFR-β疗法，并且这两个基因都是未来肿瘤学检测的潜在候选基因。
