Drug dose and drug choice: Optimizing medical therapy for veterinary cancer

Although novel agents hold great promise for the treatment of animal neoplasia, there may be room for significant improvement in the use of currently available agents. These improvements include altered dosing schemes, novel combinations, and patient‐specific dosing or selection of agents. Previous studies have identified surrogates for “individualized dose intensity,”, for example, patient size, development of adverse effects, and pharmacokinetic parameters, as potential indicators of treatment efficacy in canine lymphoma, and strategies for patient‐specific dose escalation are discussed. Strategies for treatment selection in individual patients include conventional histopathology, protein‐based target assessment (eg, flow cytometry, immunohistochemistry, and mass spectrometry), and gene‐based target assessment (gene expression profiling and targeted or global sequencing strategies). Currently available data in animal cancer evaluating these strategies are reviewed, as well as ongoing studies and suggestions for future directions.     

The controversial histologic classification of canine subcutaneous whorling tumours: The path to perivascular wall tumours

Subcutaneous spindle cell tumours characterized by whorling growth patterns are common in dogs and are identified as a distinct entity. These tumours were misnamed as hemangiopericytomas (HPCs) because of some minor morphological parallels with their human counterparts. In veterinary medicine, the cell of origin of HPC has been under debate for a long time. Some authors have suggested a perivascular origin while others a perineural one. The evidence of the orientation of the neoplastic cells around the vessels and the expression of contractile proteins supported a perivascular origin while S100 expression and an inconsistent vascular connection supported a perineural origin. Despite the morphological similarities with peripheral nerve sheath tumours in humans, the perineural origin was supported mainly by the expression of markers with low specificity. On the contrary, the majority of studies have supported the perivascular origin of ‘old’ canine HPC. Since a variable degree of myoid‐pericytic differentiation was described, the term perivascular wall tumours (PWTs) were suggested to substitute HPC. Once the diagnostic criteria of PWTs were defined, the clinical behaviour and prognostic variables were investigated, demonstrating differences as compared with the group of canine soft tissue sarcomas (STSs) in general. PWTs are less aggressive, mostly locally invasive, and rarely metastasizing. Their behaviour seems to be less influenced by histological grade, suggesting that canine STSs are heterogeneous. The study of the biological behaviour of specific STS tumour types may be valuable in detecting differences which have passed unnoticed when STSs have been studied concomitantly.     

犬猫冠状病毒研究进展

犬冠状病毒（canine coronavirus,CCoV）与猫冠状病毒（feline coronavirus,FCoV）同属于冠状病毒科冠状病毒属α属,与其同属的病毒还有猪传染性胃肠炎病毒（porcine transmissible gastroenteritis virus,TGEV）、猪流行性腹泻病毒（porcine epidemic diarrhea virus,PEDV）等。遗传进化分析表明,该种属不同基因型病毒通过基因重组能产生新型变异毒株,为疾病的诊断与防控造成了很大的阻碍。β属冠状病毒包括牛冠状病毒（bovine coronavirus,BCoV）、犬呼吸道冠状病毒（canine respiratory coronavirus,CRCoV）、严重急性呼吸综合征冠状病毒（severe acute respiratory syndrome coronavirus,SARS-CoV）等,其中CRCoV与BCoV同源性较高,该类病毒与α属冠状病毒在基因组结构、致病机制、感染症状等方面差异较大。CCoV与FCoV在全球范围内广泛传播,具有发病率高、死亡率低的特点。由于RNA病毒本身的特点和环境选择压力的影响,这两种病毒不断变异进化,新的强致病力毒株相继出现。经FCoV基因突变演化而来的猫传染性腹膜炎病毒（feline infectious peritonitis virus,FIPV）毒力大大增强,病毒基因组中某些特异性的点突变使得针对宿主的细胞嗜性发生改变,该病毒的致病机制主要依赖于病毒感染后诱导机体产生的抗体依赖性增强作用（ADE）。针对犬猫冠状病毒的流行病学调查及防控不能仅依赖于疫苗免疫单一因素,还应综合考虑病毒毒力、环境条件、宠物自身免疫抵抗力状态等。针对犬猫冠状病毒的诊断应根据临床症状,结合常规血液学检查、血清生化检查和实验室诊断技术来进行全面的鉴定,防止出现假阳性及假阴性结果。     

犬肺表面活性蛋白A的克隆及其在昆虫杆状病毒系统的表达

利用RT-PCR方法扩增犬肺表面活性蛋白Ａ（canine lung surfactant protein A, cSP-A）基因,将其连接至pMD18-T载体,经测序正确后,使用DNAMAN软件比对不同种属SP-A基因序列;将cSP-A基因片段经双酶切后连接至pFastbac1载体得到pFastbac1-cSP-A;再将其转化至DH10Bac感受态细胞,获得重组Bacmid质粒,然后转染sf9细胞得到P1代重组杆状病毒P1 rBv-cSP-A,P1 代病毒连续扩增3代后,取P4 rBv-cSP-A感染sf9细胞表达cSP-A重组蛋白,利用蛋白免疫印迹和间接免疫荧光试验鉴定表达产物。结果显示cSP-A基因大小为699 bp;不同种属间SP-A 的C末端碳水化合物识别结构域的同源性为49.1% ～95.5%;经Western Blot和IFA鉴定,重组cSP-A蛋白在细胞内表达未分泌到胞外,分子量大小约为31.84 kDa。