血管内皮生长因子在犬乳腺癌裸鼠模型中的表达及其意义

乳腺是犬肿瘤常发的部位，母犬乳腺瘤发病率约占全部肿瘤性疾病的25％～42％，这种疾病在公犬很少发病（低于3％）。乳腺肿瘤疾病在犬5岁之前很少发生，但随着年龄的增长，发病率逐渐上升。大多数的试验证明犬的乳腺肿瘤疾病发病年龄集中在10～12岁。乳腺肿瘤中约有一半是恶性的，并且发生转移的比率很高。据报道，母犬患乳腺肿瘤的机率是人类女性患乳腺肿瘤的3倍，犬乳腺肿瘤在组织形态学与生理学上与人类乳腺肿瘤基本一致。因此犬的原发性乳腺肿瘤是研究人类乳腺肿瘤极好的模型。     

实时荧光定量PCR对犬乳腺肿瘤组织TNFR1基因的定量检测

乳腺肿瘤是母犬中最为常见的肿瘤,运用实时荧光定量PCR检测了37例犬乳腺肿瘤病例和37份正常乳腺组织.结果表明:犬乳腺肿瘤组织中肿瘤坏死因子受体(TNFR1)的表达量显著低于正常对照组织(P<0.05).该试验结果说明,犬乳腺肿瘤的发生很可能与TNFR1表达降低有关,为深人研究肿瘤形成的分子机理提供了重要参考.     

10例犬乳腺肿瘤病理组织学分析

犬乳腺肿瘤的研究受到国内外学者的重视.一方面是因为它是兽医临床中的常见病,约占雌犬所有肿瘤的50%(Nakagawa,2001),占母犬生殖系统疾病的82%,是犬肿瘤性疾病中最为重要的类型之一;另一方面是因为犬乳腺肿瘤在发病原因、组织学来源、分类以及转移等方面都与人乳腺肿瘤相似,是很好的人乳腺癌的动物模型(Jia-Lin Lee等,2004).     

手术治疗犬的乳腺肿瘤

肿瘤是机体正常组织细胞在不同始动与促进因素的长期作用下形成的病理性产物，在医学上有良性肿瘤与乳腺肿瘤之分。母犬的乳腺肿瘤发病率较高，约占犬肿瘤疾病的25％～42％，其中约有50％为恶性肿瘤。大量临床研究表明，犬的乳腺肿瘤多发生于10岁以上的成年母犬，     

一例老年犬乳腺肿瘤的诊治

乳腺肿瘤是一种常见的肿瘤性疾病，多发于未绝育的老年雌性犬，其发病年龄主要在8～12岁，雄性犬病例少见。详细介绍了一例犬乳腺肿瘤的诊断与治疗方案，患犬为10岁老年雌性犬，经临床检查及病理学检查最终确诊为恶性肿瘤，经手术及药物治疗后出院。     

犬的乳腺肿瘤切除手术的体会

犬的乳腺肿瘤是犬生殖系统最常见的肿瘤，占生殖系统肿瘤的82％。有良性肿瘤和恶性肿瘤之分。常发生于10～1l岁老年母犬，2岁以下的犬少发。纯种犬发病率高于杂种犬，无产仔犬高于产仔犬；肿瘤中恶性肿瘤约占40％，良性肿瘤主要有腺瘤、纤维腺瘤约占50％，此外肉瘤与混合瘤各占4％。乳腺肿瘤发生与激素有关，摘除后易复发或转移到其它脏器。治疗最佳方法是手术。结合本人实践要做好肿瘤切除几个要点，现报道如下：     

犬猫乳腺肿瘤的病理诊断方法与临床治疗

乳腺肿瘤疾病是兽医临床上常见的一种母犬母猫肿瘤疾病,约占母犬母猫肿瘤疾病总发病率的50%,但在公犬公猫并不常见.根据对乳腺肿瘤病理学检查的统计,50%以上的乳腺肿瘤为良性.据国外文献记载乳腺肿瘤是犬猫(不论公母)所有常见肿瘤中排名第2的肿瘤(排名第1的是皮肤肿瘤),而全世界所记载的犬猫乳腺肿瘤发生频率并没有地理上的差别.     

犬乳腺瘤治疗的观察分析

通过对21例犬乳腺肿瘤临床病例的调查,得到如下结论:犬乳腺肿瘤的易患犬类型为德国牧羊犬、京巴犬和西施犬;易患犬发病年龄为5～8岁;易发病位置为犬的倒数第一二对乳腺;在21例病例中良性肿瘤16例,所占比例为76.19%;恶性肿瘤5例,占23.81%。良性肿瘤质地坚硬,有较完整的包膜覆盖,并形成较为明显的肿块。恶性     

犬乳腺肿瘤的诊治1例

犬乳腺肿瘤在母犬中非常常见,是仅次于皮肤肿瘤的最常见肿瘤,母犬的发生率约0.2%,大约50%的犬乳腺肿瘤是恶性的。犬后面几个乳腺发生肿瘤的可能性更大,因它们相对大一些,含的细胞略多一些,恶变的可能性也大一些。笔者近日诊断并治疗了一病例,     

microRNA在犬乳腺肿瘤中的研究进展

犬乳腺肿瘤(CMT)在许多方面与人类乳腺癌(HBC)相似，是雌犬死亡率最高的常见肿瘤。到目前为止，大多数犬乳腺肿瘤仅在临床上乳腺发生可见变化时才被发现，手术切除肿块是较为有效的治疗方法。为了在肉眼可见变化之前发现恶性肿瘤，应考虑评估血清或体液中生物标志物。微核糖核酸(miRNA)作为转录后基因调控因子，已成为肿瘤研究中具有吸引力的生物标志物。本文从miRNA的来源、作用机制、与肿瘤发生发展的关系、检测方法、作为生物标志物的应用前景和局限性等方面，综述了miRNA在犬乳腺肿瘤中的研究现状和作为生物标志物在早期临床诊断或癌症进展监测中的应用价值，为犬乳腺肿瘤早期诊断和预后分析应用提供参考。     

Cyclooxygenase-2 expression in canine mammary tumors

Mammary tumors are the most common neoplasms in female dogs. Induction of cyclooxygenase-2 (COX-2) has been implicated in various cancers in humans. However, expression of COX-2 has not been investigated in canine mammary tumors. Normal mammary gland (n = 4), simple or complex adenomas (n = 63), and simple or complex adenocarcinomas (n = 84) were studied by immunohistochemistry. Results showed that COX-2 was not expressed in the normal gland but was detected in 24% of adenomas and in 56% of adenocarcinomas (P < 0.001). The incidence of COX-2 expression and the intensity of the COX-2 signal were higher in adenocarcinomas than in adenomas (P < 0.001). These results demonstrate for the first time that COX-2 is induced in a proportion of canine mammary tumors and that COX-2 expression is more frequent and more intense in malignant than in benign tumors, suggesting a potential role for COX-2 in canine mammary tumorigenesis.     

Immunohistochemical analysis of cyclin A, cyclin D1 and P53 in mammary tumors, squamous cell carcinomas and basal cell tumors of dogs and cats

The involvement of cyclin A, cyclin D1 and p53 proteins in canine and feline tumorigenesis was analyzed immunohistochemically. In the present study, a total of 176 cases were examined, among which there were 108 canine cases (75 mammary lesions, 16 squamous cell carcinomas and 17 basal cell tumors) and 68 feline cases (43 mammary lesions, 20 squamous cell carcinomas and 5 basal cell tumors). Speckled nuclear staining for cyclin A was observed in 19/38 (50%) canine malignant mammary tumors and 18/37 (48.6%) feline mammary carcinomas, while this was not seen in benign mammary tumors of either dogs or cats. Marked intense nuclear cyclin A staining was seen in 7/16 (43.8%) canine squamous cell carcinomas and 18/20 (90.0%) feline squamous cell carcinomas. Only 3/17 (17.6%) canine basal cell tumors showed slight and scattered staining for cyclin A. Expression of cyclin D1 was very rare in both canine and feline tumors. Nuclear staining of p53 was found in 7/37 (18.9%) feline mammary carcinomas. Intense immunoreactivity for p53 was found in 6/16 (37.5%) canine squamous cell carcinomas and 8/20 (40%) feline squamous cell carcinomas. These results suggest that cyclin A may have a role in the proliferation of canine malignant mammary tumors, feline mammary carcinomas and squamous cell carcinomas of dogs and cats, and p53 may associate with the tumorigenesis of feline mammary carcinomas and squamous cell carcinomas of dogs and cats.     

Amplification of the cyclin A gene in canine and feline mammary tumors

DNAs from 33 canine mammary tumors and 8 feline mammary carcinomas were examined by Southern blot analysis to clarify genomic abnormalities of the cyclin A gene. Amplification of cyclin A was detected in 27.3% (9/33) of canine mammary tumors and 87.5% (7/8) of feline mammary carcinomas. It was suggested that amplification of cyclin A do not correlate directly with the tumorigenesis of canine mammary tumors, because there was no significant difference of incidence of cyclin A amplification between the benign and malignant tumors. In feline mammary carcinomas, the high frequency of cyclin A amplification raised the possibility that the amplification lead to the protein overexpression and play an important role in the tumorigenesis.     

Immunohistochemical expression of estrogen receptor beta in normal and tumoral canine mammary glands

To date, two isoforms of estrogen receptors (ER) have been identified, cloned, and characterized from several species, estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta). Although the presence of ERalpha has been demonstrated in normal and tumoral canine mammary tissues, the issue of ERbeta expression has not been addressed in the dog. In this study, we have analyzed the expression of ERbeta in formalin-fixed, paraffin-embedded tissue samples of nonaltered mammary gland, 30 malignant (six complex carcinoma, 12 simple carcinoma, three carcinosarcoma, and nine carcinoma or sarcoma in benign tumor), and five benign (one fibroadenoma, one complex papilloma, one complex adenoma, and two benign mixed tumors) mammary tumors of the dog by using a polyclonal ERbeta antibody and the avidin-biotin-peroxidase complex immunohistochemical technique. Our results show that high numbers of normal ductal and acinar epithelium and approximately one third of canine mammary tumors express ERbeta. This expression was higher in benign than in malignant tumors. Furthermore, expression was higher in complex and mixed histologic subtypes of malignant tumors when compared with simple subtypes.     

一例犬乳腺导管乳头状癌的诊断与治疗

犬乳腺导管乳头状癌是犬乳腺肿瘤的一种,为恶性肿瘤,多发于中老年未绝育母犬。临床症状为乳腺出现肿块,大小不等,生长快速,肿瘤可以在一个或多个腺体中发展。在晚期转移的情况下,癌变会扩散到淋巴结,肺,结肠,肾脏,有时还会扩散到骨骼,及早施行手术通常预后良好。本文对一例8岁母犬的乳腺导管内乳头状癌病例的临床诊断与手术治疗情况作详细介绍,以期为犬乳腺肿瘤的临床诊治提供参考。     

Abnormal structure of the canine oncogene, related to the human c-yes-1 oncogene, in canine mammary tumor tissue.

Cellular oncogenes of genomic DNA in 6 canine primary mammary tumors were screened by Southern blot analysis, using 7 oncogene probes. A canine genomic oncogene related to the human c-yes-1 oncogene was detected as abnormal bands in solid carcinoma genomic DNA digested with EcoRI, HindIII, HindIII-EcoRI, or HindIII-BamHI. Comparison was made between other tumor specimens and control specimens obtained from 4 clinically normal dogs--1 mixed breed and 3 Shiba Inu dogs (the same breed as the dog from which the solid carcinoma was obtained). These abnormal bands were 0.1 to 1 kilobase shorter than the normal gene. However, digestion of genomic DNA obtained from normal WBC of this dog also produced all of the abnormal bands as observed in digested DNA from the solid carcinoma tissue. Therefore, in this dog, the genomic DNA of all somatic cells from the ontogenic stage still had the abnormal sequences related to the human c-yes-1 oncogene, and it is possible that this abnormal structure may have some role (eg, as an initiator) in tumorigenesis or the progression of this tumor.     

Molecular carcinogenesis of canine mammary tumors: news from an old disease

Studies focusing on the molecular basis of canine mammary tumors (CMT) have long been hampered by limited numbers of molecular tools specific to the canine species. The lack of molecular information for CMT has impeded the identification of clinically relevant tumor markers beyond histopathology and the introduction of new therapeutic concepts. Additionally, the potential use for the dog as a model for human breast cancer is debatable until questions are answered regarding cellular origin, mechanisms, and cellular pathways. During the past years, increasing numbers of canine molecular tools have been developed on the genomic, RNA, and protein levels, and an increasing number of studies have shed light on specific aspects of canine carcinogenesis, particularly of the mammary gland. This review summarizes current knowledge on the molecular carcinogenesis of CMT, including the role of specific oncogenes, tumor suppressors, regulators of apoptosis and DNA repair, proliferation indices, adhesion molecules, circulating tumor cells, and mediators of angiogenesis in CMT progression and clinical behavior. Whereas the data available are far from complete, knowledge of molecular pathways has a significant potential to complement and refine the current diagnostic and therapeutic approach to this tumor type. Furthermore, current data show that significant similarities and differences exist between canine and human mammary tumors at the molecular level. Clearly, this is only the beginning of an understanding of the molecular mechanisms of CMT and their application in clinical patient management.     

Novel variations and loss of heterozygosity of BRCA2 identified in a dog with mammary tumors

OBJECTIVE: To establish novel polymorphic markers for analysis of loss of heterozygosity (LOH), so as to study the possible involvement of BRCA2 in mammary tumors obtained from dogs. SAMPLE POPULATION: Blood samples, mammary gland specimens, or mammary tumors from 3 tumor-bearing dogs and 10 tumor-free dogs. PROCEDURES: Nucleotide sequence analysis was performed with a DNA autosequencer. Loss of heterozygosity analysis was performed for markers established in the present study. The expression level of canine BRCA2 was quantified by real-time PCR analysis. RESULTS: 3 novel microsatellite markers with high heterozygosity rates (> 50%) were established, and the previously reported marker for canine BRCA2 gene locus was improved. These markers were used for the analysis of DNA from formalin-fixed and paraffin-embedded samples. By use of these markers, LOH in canine BRCA2 was identified as a result of recombination. In mammary tumor DNA that corresponded to the LOH-positive dog, the level of canine BRCA2 expression was decreased compared with that of nonneoplastic mammary gland tissue; the open reading frame contained 4 missense variations, 1 insertion variation, and 1 silent variation, some of which were localized to functional domains. CONCLUSIONS AND CLINICAL RELEVANCE: 3 novel polymorphic markers were developed for LOH analysis of canine BRCA2 and identified a dog with LOH with some variations in the functional domains. These markers could be useful for assessing the relevance of BRCA2 variation in mammary tumors of dogs.     

Expression patterns of the BRCA1 splicing variants in canine normal tissues and mammary gland tumors

Human BRCA1 is familial breast cancer susceptibility gene. Recently, decreased BRCA1 mRNA and protein expression has been identified in sporadic breast tumors. In the reported human BRCA1 splicing variants, delta11b lacks the majority of exon11 and is suspected to have a distinct function in normal tissues. The splicing variants display a variety of expression pattern in breast cancer samples. Although mammary gland tumor is important disease in dog, there are few reports for BRCA1 in the canine tumors. In this study, we examined the relative amounts of BRCA1 splicing variants mRNA in canine normal and mammary tumor samples by RT-PCR to investigate whether there is the altered expression of variant mRNAs in the canine tumor as reported in human. The exon11b-defecting RT-PCR products were observed in all the normal tissues examined and the nucleotide sequence was quite similar to that of human BRCA1 delta11b. In some tumor samples, we did not detect the products targeted for exon10-13 and exon14-15, while these products were observed in all the normal samples examined. Especially, the relative amounts of the exon11-defecting products were remarkably decreased in most of the tumors (11/16).