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Marek Szczubiał Marta Kankofer Jacek Wawrzykowski Roman Dąbrowski Wojciech Łopuszyński Mariola Bochniarz Piotr Brodzki 《Reproduction in domestic animals》2020,55(10):1404-1410
In the present study, the concentration of decorin in canine normal and neoplastic mammary gland tissues was examined to understand the potential role of decorin in development and progression of canine mammary tumours. The homogenates of 48 mammary gland tumours (10 benign and 38 malignant) and 10 samples of normal canine mammary gland tissue were used in the study. The presence and quantification of decorin was examined in the homogenates using Western blot and specific canine ELISA. Western blotting confirmed the presence of decorin both in the normal mammary gland tissues and in the mammary gland tumours. The concentration of decorin was significantly higher (p < .05) in the benign tumours and non-metastatic malignant tumours than in the normal mammary gland. The concentration of decorin was significantly lower (p < .05) in the malignant tumours with metastasis to regional lymph nodes compared with benign tumours and non-metastatic malignant tumours. No significant differences were found in the level of decorin between the benign and the non-metastatic malignant tumours. Both the histological type of malignant tumours and the histological grade did not significantly affect the concentration of decorin. These findings suggest that neoplastic transformation in the canine mammary gland leads to increase in the decorin protein synthesis. The reducing decorin concentration in canine malignant mammary tumours appears to facilitate the metastatic spread of these tumours. 相似文献
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To explore the expression and clinical importance of the anti-oncogene phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in canine mammary gland tumours, PTEN expression was compared in 50 cases of canine mammary tumour and four examples of normal mammary tissue using real-time quantitative PCR. PTEN expression was similar in benign mammary tumours and normal mammary tissues (P>0.05), but was lower in malignant tumours than in normal mammary tissues or benign mammary tumours (P<0.001). PTEN expression was also low in the lymph node metastases of malignant mammary tumours. The expression profile of PTEN in malignant mammary tumours compared to those without lymph node metastasis varied significantly. Low-level PETN expression might play an important role in carcinogenesis and the progression of canine mammary tumours, and PTEN protein detection might be useful in evaluating tumour development and prognosis. 相似文献
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Properties of the feline tumour suppressor reduced expression in immortalized cells (REIC/Dkk‐3) 
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下载免费PDF全文 K. Ochiai H. Oda S. Shono Y. Kato S. Sugihara S. Nakazawa D. Azakami M. Michishita E. Onozawa M. Bonkobara T. Sako L. Shun‐Ai H. Ueki M. Watanabe T. Omi 《Veterinary and comparative oncology》2017,15(4):1181-1186
Reduced expression in immortalized cells (REIC/Dkk‐3), a member of the human Dickkopf (Dkk) family, is a growth suppressor in human and canine mammary tumours. Mammary gland tumours are common neoplasms with high malignancy in female cats. The purpose of this study was to clone the feline REIC/Dkk‐3 homolog, investigate its expression in cell lines established from feline mammary gland tumours, and test its tumour suppressor function. Western blot analysis revealed that expression of the REIC/Dkk‐3 protein was reduced in feline mammary carcinoma cell lines. Forced expression of REIC/Dkk‐3 induced apoptosis in feline mammary tumour cell lines. These results demonstrate that REIC/Dkk‐3 expression, which is downregulated in feline mammary tumour cell lines, results in the induction of apoptosis in these cells. Our findings suggest that feline REIC/Dkk‐3 represents a potential molecular target for the development of therapies against feline mammary cancers. 相似文献
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Murai K Nakagawa T Endo Y Kamida A Yoshida K Mochizuki M Nishimura R Sasaki N 《Research in veterinary science》2012,93(1):468-472
We produced 23 cloned cell lines from parental CHMp, which was previously established from a canine mammary adenocarcinoma patient in our laboratory. Two representative cloned cell lines, namely, CHMp-5b and -13a, were selected and characterized for cellular morphology, growth potential and expression of some tumour-related proteins. Subsequently, we transplanted the 2 tumour cell lines orthotopically into female nude mice to examine their tumorigenicity and metastatic potential. Interestingly, despite sharing the same origin, only CHMp-5b cells metastasized to the lung. Our results indicate that a comparison between these 2 cell lines at the molecular level will help us understand mechanisms of tumour progression, especially in the context of distant metastases originating from canine mammary gland tumours. 相似文献
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Fifty-two spontaneous canine mammary gland tumours (fibroadenomas (n = 8), tubulopapillary carcinomas (n = 9), solid carcinomas (n = 6), anaplastic carcinomas (n = 7), fibrosarcomas (n = 9), liposarcomas (n = 9) and osteosarcomas (n = 4) were analysed by computer-assisted nuclear morphometry in Hemacolor-stained cytological specimens. Computerized cytomorphometry
was performed and the nuclear area, nuclear perimeter and mean nuclear diameter of investigated tumours were assessed. A minimum
of 100 nuclei per lesion were examined. The statistical analysis revealed statistically significant differences between benign
and malignant neoplasms. The results indicated that computer-assisted nuclear morphometry could be used as an additional method
for differentiation of benign from malignant canine mammary gland tumours in cytological specimens. 相似文献
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Dual targeting of EGFR and ERBB2 pathways produces a synergistic effect on cancer cell proliferation and migration in vitro 下载免费PDF全文
下载免费PDF全文 M. E. Gray S. Lee A. L. McDowell M. Erskine Q. T. M. Loh O. Grice D. J. Argyle G. T. Bergkvist 《Veterinary and comparative oncology》2017,15(3):890-909
Members of the epidermal growth factor receptor (EGFR/ERBB) gene family are frequently dysregulated in a range of human cancers, and therapeutics targeting these proteins are in clinical use. We hypothesized that similar pathways are involved in feline and canine tumours and that the same drugs may be of clinical use in veterinary patients. We investigated EGFR and ERBB2 targeting using a panel of feline and canine cell lines. EGFR and ERBB2 were targeted with siRNAs or tyrosine kinase inhibitors (TKIs) and their effect on cellular proliferation, colony formation and migration was investigated in vitro. Here we report that EGFR and ERBB2 combined siRNA targeting produced synergistic effects in feline and canine cell lines similar to that reported in human cell lines. We conclude that dual EGFR and ERBB2 targeting using TKIs should be further evaluated as a potential new therapeutic strategy in feline head and neck and mammary tumours and canine mammary tumours. 相似文献
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Masaya IGASE Chung Chew HWANG Matt COFFEY Masaru OKUDA Shunsuke NOGUCHI Takuya MIZUNO 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2015,77(5):541-548
Oncolytic virotherapy is a new strategy for cancer treatment for humans and
dogs. Reovirus has been proven to be a potent oncolytic virus in human medicine. Our
laboratory has previously reported that canine mast cell tumor and canine lymphoma were
susceptible to reovirus. In this study, canine solid tumor cell lines (mammary gland
tumor, osteosarcoma and malignant melanoma) were tested to determine their susceptibility
towards reovirus. We demonstrated that reovirus induces more than 50% cell death in three
canine mammary gland tumors and one canine malignant melanoma cell line. The
reovirus-induced cell death occurred via the activation of caspase 3. Ras activation has
been shown to be one of the important mechanisms of reovirus-susceptibility in human
cancers. However, Ras activation was not related to the reovirus-susceptibility in canine
solid tumor cell lines, which was similar to reports in canine mast cell tumor and canine
lymphoma. The results of this study highly suggest that canine mammary gland tumor and
canine malignant melanoma are also potential candidates for reovirus therapy in veterinary
oncology. 相似文献
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K. U. Sorenmo V. M. Kristiansen M. A. Cofone F. S. Shofer A.‐M. Breen M. Langeland C. M. Mongil A. M. Grondahl J. Teige M. H. Goldschmidt 《Veterinary and comparative oncology》2009,7(3):162-172
This study describes the clinical and histopathological findings in dogs with mammary gland tumours, and compares the histopathological and clinical evidence consistent with progression from benign to malignant to human breast cancer epidemiology. Clinical and histopathological data on 90 female dogs with 236 tumours was included. Dogs with malignant tumours were significantly older than dogs with benign tumours (9.5 versus 8.5 years), P = 0.009. Malignant tumours were significantly larger than benign tumours (4.7 versus 2.1 cm), P = 0.0002. Sixty‐six percent had more than one tumour, and evidence of histological progression was noted with increasing tumour size. Dogs with malignant tumours were significantly more likely to develop new primary tumours than dogs with benign tumours, P = 0.015. These findings suggest that canine mammary tumours progress from benign to malignant; malignant tumours may be the end stage of a histological continuum with clinical and histopathological similarities to human breast carcinogenesis. 相似文献
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Petterino C Rossetti E Bertoncello D Martini M Zappulli V Bargelloni L Castagnaro M 《Journal of veterinary medicine. A, Physiology, pathology, clinical medicine》2006,53(4):174-178
Elevated levels of P-glycoprotein have been reported in multidrug-resistant tumours in both humans and dogs. In the present study, we investigated the expression of P-glycoprotein in 57 canine mammary gland tumours, 10 mammary gland hyperplasia and seven normal mammary glands by immunohistochemistry. Tissue sections were incubated with an anti-Pgp monoclonal antibody and visualized with En Vision-DAB polymer. Normal and hyperplastic mammary tissues were negative or showed slight cytoplasmic immunoreactivity. Neoplastic cells in benign mammary tumours showed diffuse cytoplasmic staining, in contrast to malignant tumours that showed mainly a membranous staining pattern for Pgp (C494). We observed statistically significant differences among all the different groups of tissues analysed except for benign tumours versus hyperplasia (P = 0.221). Receiver-operating characteristic analysis showed that the best cut-off point to differentiate the threshold to differentiate negative from positive tissue samples was 18.40% of immunostained cells. These results provide a first indication that routine evaluation of Pgp expression in canine mammary gland tumours, taking into consideration a cut-off point for positivity, may be useful for selecting cases for chemotherapy. 相似文献
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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。 相似文献
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J.H. Vos T.S.G.A.M. van den Ingh W. Misdorp R.F. Molenbeek F.N. van Mil G.R. Rutteman 《The Veterinary quarterly》2013,33(3):96-102
Summary Ten malignant canine mammary gland tumours and five metastases from three of these tumours were studied immunohistochemically with monoclonal antibodies (MoAbs) directed against different human keratin types (K), α‐smooth muscle actin, vimentin, and desmin. In all tumours the neoplastic epithelium was rather homogeneously labelled with the keratin MoAbs RCK 102 (K 5 and 8) and CAM 5.2 (K 8). The adenocarcinomas (n=5), the solid carcinomas (n=2), and the carcinosarcoma (n=1) showed heterogeneous labelling with the MoAbs specific for luminal cell antigens in the normal canine mammary gland, i.e., K 18, K 7 and K 19 MoAbs. These cells were also immunoreactive with K 4 and K 10 MoAbs. The spindle cell carcinomas (n=2), however, did not react with these MoAbs. All tumours except one adenocarcinoma were characterized by the absence of immunoreactive labelling with the α‐smooth muscle actin MoAb. In the solid carcinomas this was associated with the absence of labelling with one or both basal cell specific keratin MoAbs, i.e., 8.7 (K 14 and 17) and RCK 107 (K 14), respectively. In contrast, the other malignant tumours showed marked labelling of neoplastic epithelium with these MoAbs. Another remarkable finding was the labelling of a limited to moderate number of neoplastic epithelial cells with the vimentin MoAb. The presence of such labelling patterns in canine mammary gland tumours may be indicative of malignancy. Metastatic tumour tissues had a labelling pattern largely similar to that of the primary tumour, although also loss of reactivity for some keratin MoAbs was seen. 相似文献
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C Cocola P Anastasi S Astigiano E Piscitelli P Pelucchi L Vilardo G Bertoli M Beccaglia MC Veronesi S Sanzone O. Barbieri RA Reinbold GC Luvoni I Zucchi 《Reproduction in domestic animals》2009,44(S2):214-217
Recent data suggest that mammary carcinogenesis may be driven by cancer stem cells (CSCs) derived from mutated adult stem cells, which have acquired aberrant cell self-renewal or by progenitor cells that have acquired the capacity for cell self-renewal. Spontaneous mammary cancers in cats and dogs are important models for the understanding of human breast cancer and may represent alternative species model systems that can significantly contribute to the study of human oncogenesis. With the goal of identifying markers for isolating human breast CSCs, we have generated a canine model system to isolate and characterize normal and CSCs from dog mammary gland. Insight into the hierarchical organization of canine tumours may contribute to the development of universal concepts in oncogenesis by CSCs. Cells with stem cell properties were isolated from normal and tumoural canine breast tissue and propagated as mammospheres and tumourspheres in long-term non-adherent culture conditions. We showed that cells obtained from spheres that display self-renewing properties, have multi-lineage differentiation potential, could generate complex branched tubular structures in vitro and form tumours in NOD/SCID mice. We analysed these cells for the expression of human stem and CSC markers and are currently investigating the tumour-initiating properties of these cells and the hierarchical organization of normal and neoplastic canine mammary tissue. 相似文献
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Gama A Paredes J Gärtner F Alves A Schmitt F 《Veterinary journal (London, England : 1997)》2008,177(1):45-53
Cadherin-catenin complexes play a critical role in intercellular adhesion, and their altered expression has been implicated in tumour progression. In this study, the expression of E-cadherin, P-cadherin and beta-catenin was analysed in 65 canine malignant mammary tumours and correlated with clinicopathological parameters, proliferation and survival. Reduction in E-cadherin expression was significantly associated with increased tumour size, high histological and invasion grades, lymph node metastasis and high mitotic index. Reduced beta-catenin expression was associated with high histological and invasion grades. Anomalous expression of P-cadherin was only associated with invasion. In 39 cases for which follow-up data were available, reduced E-cadherin and beta-catenin expression was significantly associated with shorter overall survival and disease free survival. Abnormal expression of adhesion molecules is a common phenomenon in canine mammary malignant tumours and may play a central role in tumour progression. 相似文献
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F G?rtner M Geraldes G Cassali A Rema F Schmitt 《Veterinary journal (London, England : 1997)》1999,158(1):39-47
DNA measurement by image cytometry, and a detailed immunohistochemical study using monoclonal antibodies directed against different human cytokeratin types, muscle-specific actin, vimentin and S100 protein were carried out on normal canine mammary tissue (n =4), benign canine mammary mixed tumours (n =20) and malignant canine mammary mixed tumours (n =13). The results showed that ductal and alveolar luminal cells in normal and neoplastic tissue were immunoreactive with CAM5.2 and AE1/AE3 antibodies recognizing human keratins.Basal/myoepithelial cells were clearly differentiated from ductal and alveolar epithelial cells, since the latter only expressed cytokeratins, whereas the former also expressed vimentin and muscle-specific actin. This immunohistochemical study showed that there is loss of expression of muscle-specific actin and cytokeratins in areas of myoepithelial proliferation, and enhanced expression of vimentin and S100 protein in proliferative areas with osseous and/or chondroid metaplasia. The ploidy studies revealed that 20% (4/20) of benign and 54% (7/13) of malignant mixed tumours of canine mammary gland were aneuploid and that the epithelial and myoepithelial components of the mixed tumours had identical DNA content.Our results reinforce the role of myoepithelial cells in mesenchymal metaplasia in mixed mammary tumours and suggest the possibility of a common origin of both components from a totipotential stem cell with capacity for divergent differentiation. 相似文献
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To investigate the relationship between the expression of the PTEN (phosphatase and tensin homolog deleted on chromosometen) and VEGF (vascular endothelial growth factor) and the clinicopathological features in canine mammary gland tumours, the expression levels of PTEN and VEGF protein were assessed in 50 cases of canine mammary gland tumours tissues and 4 cases of normal mammary gland tissues with using immunohistochemical method. The over-expression rate of PTEN protein was 100% in normal and well-differentiated mammary gland tissues and 67% in breast cancer cases respectively with a significant difference between the two groups (P<0.01). Expression of PTEN was not related to age and tumour size, but closely correlated to lymph node metastasis (P<0.01). The over-expression rate of VEGF protein was 33.3% in normal mammary gland tissues, and 78% in canine mammary gland tumours with a significant difference between the two groups (P<0.01).Expression of VEGF was not related to age or tumour size, but closely correlated with lymph node metastasis and clinical stage (P<0.05).Therefore the combination detection of PTEN and VEGF could serve as an important index to estimate the biological behavior and prognosis of canine mammary gland tumours. Reduced expression of PTEN might be involved in carcinogenesis and progression of canine breast cancer by up-regulating the VEGF expression to enhance angiogenesis. 相似文献
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Polymorphism of P53‐Ets/AP1 transactivation region of MDM2 oncogene and its immunohistochemical analysis in canine tumours 下载免费PDF全文
下载免费PDF全文 Mouse Double Minute‐2 (MDM2) is an ubiquitin ligase which is overexpressed or its promoter polymorphism has been reported in different tumours. The objective of this study was to examine the MDM2 protein expression and its promoter polymorphism in some canine tumours. Twenty specimens were collected from 20 dogs with 15 mammary gland carcinomas, 3 lymphomas, 1 transmissible venereal tumour and 1 trichoblastoma. Samples were analysed immunohistochemically using human antibody against MDM2 protein. PCR and DNA sequencing were carried out to identify MDM2 promoter polymorphism. MDM2 gene was expressed in 13 of 20 samples including 11 mammary carcinomas, 1 lymphoma and 1 trichoblastoma. We found 94% homology between canine and human sequences. Four mutations including G169C, A177G, G291T and A177G were identified in different types of breast carcinomas. An extra p53 response element was found in a mixed mammary carcinoma. 相似文献