Canine Tumour Suppressor Gene p53 - Mutation in a Case of Adenoma of Circumanal Glands

Highly conserved regions of the tumour suppressor gene p53, including the typical human tumour hot spots (codons 175, 245, 248, 249, 273 and 282), were investigated in various canine neoplasms. A mutation CGG TGG (arginine tryptophan) was detected in codon 249 in an adenoma of the circumanal gland.     

犬乳腺肿瘤手术治疗及其预后的调查

本研究采用单个乳腺切除、区域乳腺切除、单侧乳腺切除对临床31例犬乳腺肿瘤病例进行手术治疗,调查不同手术方法及肿瘤质量对良性、恶性乳腺肿瘤术后预后的影响。结果显示,犬乳腺肿瘤的大小与其预后相关,随着犬瘤体质重的增加,其术后预后不良愈加明显,复发率、死亡率呈上升趋势;区域乳腺摘除术或乳腺完全根除术对乳腺肿瘤患犬的预后有一定影响。     

Novel Canine Tumour Suppressor Gene p53 Mutations in Cases of Skin and Mammary Neoplasms

Exons 4 to 8 of the tumour suppressor gene p53 were analysed in 25 skin and 25 mammary tumours of 50 dogs. A 1 bp deletion (ACCAC) was detected in codon 89 in exon 4 in a squamous cell carcinoma. A missense mutation CGCCAC (argininehistidine) was present in codon 162 in exon 5 in a mammary adenocarcinoma. Moreover, a silent mutation occurred in codon 103 (serine) of exon 4 in a mammary adenoma. The somatic nature of the three mutations was demonstrated.     

p53基因与肿瘤形成

肿瘤抑制基因的研究已经成为继癌基因之后肿瘤遗传学、分子生物学领域的前沿和热点,尤其是抑癌基因p53越来越被人们重视。研究表明正常的p53,又称野生型p53,在细胞损伤后的修复过程中发挥重要作用。正常p53的功能像"分子警察"一样监视着基因组DNA的完整性。在细胞发生DNA损伤时,p53蛋白能使细胞分裂终止在G1/S期,以使细胞有足够的时间修复损伤,恢复正常状态。若不能修复,野生型p53还能启动细胞的凋亡过程从而引发细胞的程序性死亡,阻止具有癌变倾向的突变细胞产生。而突变型p53基因会导致肿瘤的发生,大多数肿瘤与p53的突变有关。文章着重阐述了p53的表达与突变、p53的稳定调节及p53的转录调控等。     

PTEN 基因在犬乳腺肿瘤组织中的表达及临床意义

有关酪氨酸磷酸酶基因（Phosphatase and tensin homolog deleted on chromosometen,PTEN）在乳腺肿瘤中的检测在人医早有报道。为了研究PTEN基因在犬乳腺肿瘤组织中的表达情况,笔者运用实时荧光PCR定量检测了38例不同的犬乳腺肿瘤组织（包括15例良性乳腺肿瘤和23例恶性乳腺肿瘤）、4例正常犬乳腺组织。结果发现：PTEN基因在犬恶性乳腺肿瘤组织中表达量明显低于其在良性乳腺肿瘤和正常乳腺组织中的表达量,两者差异极显著（P〈0.001）;PTEN在良性乳腺肿瘤组织中的表达与正常犬乳腺组织相比,差异不显著（P〉0.05）;发生了淋巴结转移的乳腺癌PTEN基因的表达量与未发生转移的乳腺癌组织的表达量间差异亦不显著（P〉0.05）,且PTEN的表达量与肿瘤组织的大小和发病动物年龄无关。结论：PTEN蛋白表达异常可能与乳腺肿瘤发生、发展相关,可考虑作为判断犬乳腺肿瘤生物学行为和预测的指标。     

犬瘟热病毒H基因变异及其细胞受体研究进展

犬瘟热(CD)是由犬瘟热病毒(CDV)引起的一种急性、高度接触性传染病。通过对CDV血凝蛋白(H)基因序列分析证实,野生动物暴发CDV野毒株感染与CDV H蛋白变异有极大关系。H蛋白主要影响CDV的抗原性、宿主范围和组织嗜性,其高变异率使CDV种间传播现象加剧,并扩大CDV宿主范围至灵长类猕猴。目前已发现2种CDV的细胞受体,即信号淋巴细胞激活因子(SLAM)和黏连蛋白4(PVRL-4/nectin-4),PVRL-4是2011年新发现的上皮细胞受体。SLAM和PVRL-4受体在哺乳动物体内的广泛存在为解释CDV对多种肉食动物具有易感性这一现象提供理论基础。论文对CDV H蛋白功能和其高变异率进行了概述,并结合H蛋白变异和其2个受体在CDV感染中的作用,以及对CDV宿主范围扩大现象进行阐述。     

奶牛NUCB2基因突变及其与产奶量关联的分析

利用PCR-SSCP和DNA测序技术首次研究了中国荷斯坦牛NUCB2基因的变异。结果表明在NUCB2基因外显子9发现两个沉默突变:27451GA和27472TC,两个碱基变化没有导致氨基酸的改变,但两个位点沉默突变同时发生,表现出3个基因型,即MM、MN和NN,经过对不同基因型与奶牛产奶量性状的关联分析,发现这些突变对奶牛产奶量产生显著影响(P0.05)。     

Canine tumour suppressor gene p53 mutation in a case of anaplastic carcinoma of the intestine

Tumours localised in the large bowel of dogs were subjected to molecular genetic studies. Highly conserved regions of the tumour suppressor gene p53, including typical tumour hot spots (codons 175, 245, 248, 249, 273 and 282), were analysed. A mutation CGG-->TGG (arginine-->tryptophan) was present in codon 249 in an anaplastic carcinoma in the caecum.     

野猪ASIP基因的突变位点及其与毛色表型的相关性研究

 本试验旨在研究影响动物被毛颜色变化的功能基因ASIP在野猪群体里的变异及其与被毛表型之间的相关性。通过直接测序法搜寻ASIP基因编码区、5′ UTR、3′ UTR和部分内含子区域突变位点。结果表明：在ASIP基因的3′ UTR区域识别了一个T→C突变位点（ASIP.c 695 T→C）,而在其它区域没用发现。通过群体内多态性检测,7个毛色类型的野猪在此突变位点都是CC或CT基因型,而长白猪群全部是TT基因型。从这个结果得出具有不同毛色的野猪群体可能是由突变位点C等位基因引起,不能排除还有其它毛色功能基因参与野猪被毛的形成。研究为进一步了解野猪ASIP毛色功能基因在其群体内的遗传变异奠定了理论基础。     

犬肥大细胞瘤诊断方法研究进展

肥大细胞瘤是犬最常见的皮肤肿瘤,其恶性率和转移率都较高,因此,探寻诊断、治疗犬肥大细胞瘤的新型有效方法就显得十分必要。论文详细介绍了两种诊断犬肥大细胞瘤的病理学分级体系,即Patnaik分级体系与Kiupel分级体系,同时解释了c-kit基因的生理作用及诊断价值,介绍了国外常用的犬肥大细胞瘤c-kit基因突变诊断方法,重点阐述了c-kit基因突变与犬肥大细胞瘤诊断、病理学分级、治疗方案的确定及预后的关系,以期能对我国小动物临床的医生和科研工作者有所启发。     

The Prognostic Significance of Angiogenesis in Canine Mammary Tumors

The purpose of the study was to determine if neovascularization, a measure of angiogenesis, is correlated with metastasis of mammary tumors in dogs. Forty-six paraffin-embedded tissue blocks of benign and malignant canine mammary tumors obtained from 42 clinical cases at the Iowa State University Veterinary Teaching Hospital were retrieved from the archives of the Department of Veterinary Pathology. Of the dogs with malignant tumors, cases with and without lymph node metastasis were chosen. Neovascularization was quantified by light microscopy on formalin-fixed, paraffin-embedded sections of canine mammary tumors using an avidin biotin immunoperoxidase assay for factor VIII-related antigen. Mean microvessel counts for each group were statistically evaluated using analysis of variance. The mean number of microvessels was highest in the malignant tumors of dogs with lymph node metastasis (44). This number was significantly different from the mean number of microvessels in the benign tumors (28; P = .03) and a trend occurred toward higher microvessel counts in malignant tumors with lymph node metastasis versus malignant tumors of dogs without metastasis (32; P = .1). No significant difference was found between the number of microvessels found in malignant tumors without metastasis versus benign tumors. The trend toward higher microvessel counts in mammary tumors that have metastasized supports the premise that angiogenesis may be an independent and significant prognostic indicator in dogs with malignant mammary tumors, as it is in women with breast cancer.     

38例犬肿瘤的病理诊断及分析

收集深圳市2010年－2012年部分宠物医院的犬肿瘤病例41例,采用组织病理学方法对犬肿瘤病例进行组织学分类,并对患病动物的年龄、性别和发生部位进行了统计分析。38例确诊肿瘤病例中,皮肤肿瘤有19例,包括鳞状细胞癌4例、基底细胞癌5例、乳头状瘤3例,皮脂腺瘤和肛周腺癌各2例,脂肪瘤、黑色素瘤、角化棘皮瘤各1例;乳腺肿瘤9例,包括乳腺癌3例、乳腺鳞状细胞癌2例、乳腺癌肉瘤2例、黏液癌1例,患犬以雌性为主;其他部位肿瘤分别有纤维肉瘤2例,血管瘤、肺癌、淋巴瘤、睾丸精原细胞瘤、睾丸支柱细胞瘤、组织细胞癌、鳞状细胞癌、乳头状瘤各1例。上述结果显示,犬肿瘤的高发部位是皮肤,其次是乳腺,其发生年龄以7岁以上为多,在发病动物的品种上没有明显差别;除乳腺肿瘤外,其余肿瘤的性别差异不大。本研究为犬肿瘤的流行病学及诊断提供了参考依据。     

Efficacy of Vinblastine for Treatment of Canine Mast Cell Tumors

Background: The optimal dosage and clinical efficacy of vinblastine (VBL) for treatment of mast cell tumors (MCTs) in dogs has not been established. Hypothesis: Single‐agent VBL has antitumor activity against MCTs in dogs. Animals: Fifty‐one dogs with nonresectable grade II or III cutaneous MCTs. Methods: Prospective, open clinical trial. Dogs were systematically allocated (by hospital record number) to receive IV treatment with VBL at a dosage of 2.0 mg/m² (weekly for 4 treatments then biweekly for 4 treatments; VBL 2.0) or treatment with VBL at a dosage of 3.5 mg/m² (biweekly for 5 treatments; VBL 3.5). The primary outcome measure was reduction in tumor size. Results: Twenty‐five dogs were allocated to the VBL 2.0 group and 26 were allocated to the VBL 3.5 group. In the VBL 2.0 group, 3 (12%) had a partial response (PR) for a median of 77 days (range, 48–229 days). Overall response rate in the VBL 3.5 group was 27%. One dog (4%) had a complete response for 63 days and 6 dogs (23%) had a PR for a median of 28 days (range, 28–78 days). Toxicoses were uncommon in the VBL 2.0 group. Twelve (46%) dogs in the VBL 3.5 group had <500 neutrophils/μL 7 days after treatment; 2 dogs with neutropenia developed concurrent fevers. Conclusions and Clinical Importance: VBL, when used as a single‐agent, has activity against MCTs in dogs although the response rate is lower than those reported for VBL‐containing combination protocols. Further, findings suggest VBL at a dosage of 3.5 mg/m² should be considered for use in future phase II/III trials.     

Removal of Five Canine Cardiac Tumors Using a Stapling Instrument

Cardiac tumors in five dogs, including four right atrial appendage hemangiosarcomas and one heartbase chemodectoma, were removed, and the excisional edges were closed with a thoracic-abdominal (TA) stapling instrument. All five dogs recovered from surgery and were discharged from the hospital within 4 days. The four dogs with atrial appendage hemangiosarcomas developed extensive metastasis, although no evidence of tumor recurrence was found at the surgical site in two dogs that were necropsied. The dog with a chemodectoma was alive with no clinical or radiographic evidence of recurrence or metastasis 17 months following surgery.     

Association between single nucleotide polymorphisms in p53 and abortion in Thoroughbred mares

Single nucleotide polymorphisms (SNPs) in the p53 gene have been studied extensively in humans. The aims of this study were to determine the frequency of the Arg/Pro SNP in p53 in Thoroughbred mares on one stud in Brazil and to correlate p53 genotypes with reproductive performance. SNPs were detected by PCR-restriction fragment length polymorphism in blood samples from 105 horses and confirmed by sequencing. The allele frequency in Thoroughbred mares at codon 72 in exon 4 was 73.3% Arg/Pro, 17.1% Arg/Arg and 9.6% Pro/Pro. The presence of Arg/Pro was significantly associated with abortion (P=0.02), while Pro/Pro mares had a lower probability of abortion (P<0.05). Using a logistic regression model, the dominance effect was significant (P=0.044; odds ratio 7.94) for abortion and additive effects were not significant (P=0.26). p53 may play a role in equine reproduction.     

A Retrospective Study of Canine Hemangiosarcoma and its Association with Acanthocytosis

A retrospective study was conducted on cases of canine hemangiosarcoma diagnosed at the Western College of Veterinary Medicine between 1969 and 1979. A total of 33 dogs were assessed with respect to breed, age, sex and site of neoplasia. Hemangiosarcoma was most common in older dogs and there was no sex predilection. Incidence was highest in German Shepherds. The primary sites in order of most frequent occurrence were spleen, right atrium and liver. Acanthocytes were found in six of 12 dogs examined. There was no association between acanthocytosis and such factors as breed, primary site of the neoplasm and splenic or hepatic involvement.