首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献，搜索用时 62 毫秒
1.
The canine transmissible venereal tumour (CTVT) is a transmissible cancer that is spread naturally between dogs, with the ability to develop and evade the immune system, despite strict immune surveillance of the host. Furthermore, molecular signalling between cells of the immune system and the tumour microenvironment appear to influence the behaviour and development of the tumour. Thus, this study aimed to quantify the expression of genes related to the immune system such as IL‐6, IFN‐γ, and TGF‐β, as well as angiogenic factors (VEGF, CXCR4), in CTVT cells in vivo and in vitro (primary culture), correlating with the clinical response of the animals treated with vincristine. As expected, the most prevalent subtype was plasmacytoid cells, although lymphocytic cells were also found, indicating the possibility of polyclonality. When we compared the gene expressions of IFN‐γ and IL‐6, we mostly found low expression, concluding that MHC expression was probably not occurring in tumour cells, and no activation of immune cells to eliminate the tumour. The TGF‐β gene was normal in the majority of animals but demonstrated decreased expression in vincristine resistant animals, leading to the hypothesis that the concentration of tumour‐derived TGF‐β was affecting and even suppressing the real TGF‐β expression, favouring tumour proliferation and progression in these cases. VEGF expression was extremely high, demonstrating its angiogenic role in tumour growth, while CXCR4 was decreased, possibly because of CTVT’s low metastatic potential. Thus, we concluded that the tumour microenvironment, together with the immune system of the host, influences CTVT, presumably altering its tumorigenesis and the animal’s clinical response to treatment.  相似文献   

2.
Four new pairs of canine mammary carcinoma cell lines derived from both primary and metastatic lesions were established. The cells were cultured in RPMI‐1640 with 10% fetal bovine serum and they showed stable growth for more than 120 passages. Using these cell lines, the expression of E‐cadherin was measured by flow cytometry and the function of E‐cadherin was evaluated by cell aggregation assay and results from the primary and metastatic lesions were compared statistically. E‐cadherin was strongly expressed in all of the cell lines, without a notable difference between cells of primary and metastatic origin. In the cell aggregation assay, the function of E‐cadherin was significantly weaker in the cells of primary origin (p < 0.05), as compared with cells of metastatic origin. The present results suggest that a reduction in E‐cadherin function may be implicated in the invasive and metastatic potential of canine mammary tumour cells; however, further study will be needed to clarify E‐cadherin function in the context of the metastasis of canine mammary carcinoma.  相似文献   

3.
Our lack of understanding of the immune microenvironment in canine osteosarcoma (cOSA) has limited the identification of potential immunotherapeutic targets. In particular, our ability to utilize readily available tissue from a dog's primary tumour to predict the type and extent of immune response in their pulmonary metastatic lesions is unknown. We, therefore, collected 21 matched pairs of primary tumours and pulmonary metastatic lesions from dogs with OSA and performed immunohistochemistry to quantify T‐lymphocyte (CD3), FOXP3+ cell, B‐lymphocyte (Pax‐5), and CD204+ macrophage infiltration. We found that T‐lymphocytes and FOXP3+ infiltrates in primary tumours positively correlated with that of metastatic lesions (ρ = 0.512, P = 0.038 and ρ = 0.698, P = 0.007, respectively), while a strong trend existed for CD204+ infiltrates (ρ = 0.404, P = 0.087). We also observed T‐ and B‐lymphocytes, and CD204+ macrophages to be significantly higher in a dog's pulmonary metastasis compared to their primary tumour (P = 0.018, P = 0.018, P = 0.016, respectively), while FOXP3+ cells were only significantly higher in metastases when all primary tumour and metastasis lesions were compared without pairing (P = 0.036). Together, these findings suggest that the metastatic immune microenvironment may be influenced by that of the primary cOSA, and that primary tumour immune biomarkers could potentially be applied to predict immunotherapeutic responses in gross metastatic disease. We, therefore, provide a rationale for the treatment of cOSA pulmonary metastases with immunotherapeutics that enhance the anti‐tumour activity of these immune cells, particularly in dogs with moderate to high immune cell infiltration in their primary tumours.  相似文献   

4.
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   

5.
Glutamine metabolism is an important metabolic pathway for cancer cell survival, and there is a critical connection between tumour growth and glutamine metabolism. Because of their similarities, canine mammary carcinomas are useful for studying human breast cancer. Accordingly, we investigated the correlations between the expression of glutamine metabolism‐related proteins and the pathological features of canine mammary tumours. We performed immunohistochemical and western blot analysis of 39 mammary tumour tissues. In immunohistochemical analysis, the expression of glutaminase 1 (GLS1) in the epithelial region increased according to the histological grade (P < .005). In the stromal region, complex‐type tumours displayed significantly higher GLS1 intensity than simple‐type tumours. However, glutamate dehydrogenase expression did not show the same tendencies as GLS1. The western blot results were consistent with the immunohistochemical findings. These results suggest that the expression of GLS1 is correlates with clinicopathological factors in canine mammary tumours and shows a similar pattern to human breast cancer.  相似文献   

6.
Spatial/temporal controls of development are regulated by the homeotic (HOX) gene complex and require integration with oncogenes and tumour suppressors regulating cell cycle exit. Spontaneously derived neoplastic canine mammary carcinoma cell models were investigated to determine if HOX expression profiles were associated with neoplasia as HOX genes promote neoplastic potential in human cancers. Comparative assessment of human and canine breast cancer expression profiles revealed remarkable similarity for all four paralogous HOX gene clusters and several unlinked HOX genes. Five canine HOX genes were overexpressed with expression profiles consistent with oncogene‐like character (HOXA1, HOXA13, HOXD4, HOXD9 and SIX1) and three HOX genes with underexpressed profiles (HOXA11, HOXC8 and HOXC9) were also identified as was an apparent nonsense mutation in HOXC6. This data, as well as a comparative analysis of similar data from human breast cancers suggested expression of selected HOX genes in canine mammary carcinoma could be contributing to the neoplastic phenotype.  相似文献   

7.
  相似文献   

8.
Cancer stem‐like cells (CSCs)/cancer‐initiating cells (CICs) are a small subpopulation of cancer cells that are responsible for the initiation, recurrence and metastasis of cancer. We previously demonstrated that, using the Hoechst 33342 dye‐based side population technique, CSCs/CICs in canine lung adenocarcinoma cell line exist. In this study, as CSCs/CICs are known to form spheres in anchorage‐independent environment in vitro, we evaluated the stemness of spheroid cells derived from canine lung adenocarcinoma and osteosarcoma cells by expression of stemness markers, and investigated radioresistance. Spheroid cells showed greater expression of stemness markers Oct‐4 and CD133 gene than those of adherent‐cultured cells. In nude mouse xenograft models, spheroid cells showed higher tumourigenic ability than adherent‐cultured cells. In addition, spheroid cells showed significantly resistant against radioactivity as compared with adherent‐cultured cells. These results suggest that spheroid cells could possess stemness and provide a CSCs/CICs research tool to investigate CSCs/CICs of canine tumour cells.  相似文献   

9.
Tumour‐associated macrophages (TAMs) have been implicated in carcinogenesis including an important role in angiogenesis. In this study, we describe the relationship between TAMs and angiogenesis in canine mammary tumours (CMT). Formalin‐fixed paraffin‐embedded CMT samples [(n = 128: malignant (n = 97) and benign (n = 31)] were submitted to immunohistochemical staining to detect MAC387, vascular endothelial growth factor VEGF and CD31 expression. A statistical analysis was carried out to assess possible associations with clinicopathological variables and biological markers of tumour angiogenesis. TAMs, detected by MAC387 expression, were significantly associated with malignant CMT (P < 0.001) and VEGF positive tumours (P = 0.002) and also associated with VEGF expression within malignant CMT (P = 0.043). Associations with clinicopathological variables were found between TAMs and the presence of infiltrative growth (P = 0.031), low tubule formation (P = 0.040) and lymph node metastasis (P = 0.016). The results support the hypothesis that TAMs influence angiogenesis in CMT suggesting TAMs may represent a therapeutic target in this disease.  相似文献   

10.
Human inflammatory breast cancer (IBC) and canine inflammatory mammary cancer (CIMC) are the most aggressive forms of mammary cancer. Current research aims to identify new therapeutic targets. Here, we investigated gene expression levels of biomarkers associated with the inflammatory microenvironment. A total of 32 formalin‐fixed paraffin‐embedded samples of canine mammary carcinoma (CIMC = 26; non‐CIMC = 6) were used and their cDNA subjected to quantitative polymerase chain reaction (qPCR) to establish gene expression levels for mediators commonly implicated in linking carcinogenesis with inflammation. Gene expression differences between CIMC and non‐CIMC types were obtained for cyclooxygenase 2 (COX‐2) (P = 0.004), synuclein gamma (SNCG) (P = 0.006), tribbles 1 (P = 0.025), vascular endothelial growth factor (VEGF) (P = 0.017) and CSF1R (P = 0.045). Among these biomarkers correlations were found, particularly between SNCG and tribbles 1 (r = 0.512, P = 0.001). The efficient metastasis of CIMC is intimately linked to components in the tumour microenvironment. This study suggests that upregulation and correlation of SNCG and tribbles 1 deserves to be further explored.  相似文献   

11.
The cancer stem cell (CSC) hypothesis proposes that tumour growth is maintained by a distinct subpopulation of ‘CSC’. This study applied flow cytometric methods, reported to detect CSC in both primary and cultured cancer cells of other species, to identify candidate canine subpopulations. Cell lines representing diverse canine malignancies, and cells derived from spontaneous canine tumours, were evaluated for expression of stem cell‐associated surface markers (CD34, CD44, CD117 and CD133) and functional properties [Hoecsht 33342 efflux, aldehyde dehydrogenase (ALDH) activity]. No discrete marker‐defined subsets were identified within established cell lines; cells derived directly from spontaneous tumours demonstrated more heterogeneity, although this diminished upon in vitro culture. Functional assays produced variable results, suggesting context‐dependency. Flow cytometric methods may be adopted to identify putative canine CSC. Whilst cell lines are valuable in assay development, primary cells may provide a more rewarding model for studying tumour heterogeneity in the context of CSC. However, it will be essential to fully characterize any candidate subpopulations to ensure that they meet CSC criteria.  相似文献   

12.
E‐cadherin is a cell adhesion molecule that participates in several cellular processes that guarantee the maintenance of structural and functional integrity of epithelial tissues. E‐cadherin plays an important role in mammary carcinogenesis, and various studies have demonstrated the effect of CDH1 genetic variation in risk, progression and biological behaviour of human breast cancer. Although there are some recognized genetic variations in canine CDH1 gene, their influence in canine mammary tumour development and progression has not been previously evaluated. In this study, we aim to assess the influence of CDH1 SNPs rs850805755, rs852280880 and rs852639930 in the risk, clinicopathological features and clinical outcome of canine mammary tumours. A case‐control study was conducted involving 206 bitches with mammary tumours and 161 bitches free of mammary neoplasia. CDH1 SNPs rs850805755 and rs852280880 were associated with a decreased risk and a later onset of mammary tumour development. Furthermore, these SNPs were related to the development of small size carcinomas, of low histological grade and low nuclear pleomorphism. SNP rs852639930 was associated with the development of small size tumours with a non‐infiltrative, non‐invasive growth pattern. Data from the present investigation demonstrate that these CDH1 genetic variants could have a protective role in canine mammary tumours, by being associated with low risk of tumour development, delayed onset of the disease and less aggressive clinicopathological features.  相似文献   

13.
The involvement of epidermal growth factor receptor (EGFR) is well established in human breast cancer, however, in canine mammary tumours (CMT), including inflammatory mammary carcinomas (IMC), still needs to be clarified. Enzyme immune assay techniques were used for EGFR determinations in tumour tissue from 45 bitches with CMT and in normal mammary glands from eight control dogs. Higher tissue EGFR levels were found in CMT compared with controls (P < 0.05). In malignant CMT, tissue EGFR elevated concentrations were statistically significantly associated with tumour relapse and/or distant metastasis during follow‐up and with reduced disease‐free and overall survival times. The IMC cases had the highest tissue EGFR levels compared with other malignant non‐IMC tumours (P < 0.001). The results support the hypothesis that EGFR levels influence prognosis in malignant CMT, suggesting that EGFR may represent a therapeutic target in cases of high histological aggressiveness and especially in cases of metastatic phenotype and poor prognosis.  相似文献   

14.
Therapy of canine mammary tumours (CMTs) with classical antitumour drugs is problematic, so better therapeutic options are needed. Palbociclib (PD‐0332991) is an innovative and effective anticancer drug for the treatment of breast cancer in women. Palbociclib is an inhibitor of cyclin‐dependent kinase 4 (CDK4) and CDK6, which are key regulators of the cell cycle machinery and thus cell proliferation. In the present in vitro study, we investigated whether Palbociclib also represents a candidate drug to combat CMT. For this purpose, the effect of Palbociclib was analysed in P114 and CF41 cells, two CMT cell lines with an endogenous CDK4/6 co‐expression. Incubation of P114 and CF41 cells with Palbociclib resulted in a dose‐ and time‐dependent loss of phosphorylated retinoblastoma protein (pRb), a classical CDK4/6 substrate within the cell cycle machinery. Moreover, treatment of CMT cells with Palbociclib‐induced cell cycle arrest affected cell viability, prevented colony formation and impaired cell migration activity. Palbociclib also inhibited the growth of P114 and CF41 cell spheroids. Immunohistochemical analysis of canine patient samples revealed a consistent expression of CDK6 in different canine mammary carcinoma types, but an individual and tumour‐specific expression pattern of phosphorylated pRb independent of the tumour grade. Together, our findings let us suggest that Palbociclib has antitumour effects on CMT cells and that canine patients may represent potential candidates for treatment with this CDK4/6 inhibitor.  相似文献   

15.
The study of the immune response in several types of tumours has been rapidly increasing in recent years with the dual aim of understanding the interactions between neoplastic and immune cells and their importance in cancer pathogenesis and progression, as well as identifying targets for cancer immunotherapy. Despite being considered one of the most immunogenic tumour types, melanoma can progress in the presence of abundant lymphocytic infiltration, therefore suggesting that the immune response is not able to efficiently control tumour growth. The purpose of this study was to investigate whether the density, distribution and grade of tumour‐infiltrating lymphocytes (TILs) in 97 canine melanocytic tumours is associated with histologic indicators of malignancy and can be considered a prognostic factor in the dog. As a further step in the characterization of the immune response in melanocytic tumours, an immunohistochemical investigation was performed to evaluate the two main populations of TILs, T‐lymphocytes (CD3+) and B‐lymphocytes (CD20+). The results of our study show that TILs are present in a large proportion of canine melanocytic tumours, especially in oral melanomas, and that the infiltrate is usually mild. The quantity of CD20+ TILs was significantly associated with some histologic prognostic factors, such as the mitotic count, the cellular pleomorphism and the percentage of pigmented cells. Remarkably, a high infiltration of CD20+ TILs was associated with tumour‐related death, presence of metastasis/recurrence, shorter overall and disease‐free survival, increased hazard of death and of developing recurrence/metastasis, hence representing a potential new negative prognostic factor in canine melanocytic tumours.  相似文献   

16.
  相似文献   

17.
Mammary tumours represent the most common neoplastic disease of the female dog, and the incidence in female dogs is much higher than in women. Whereas the influence of sexual steroids on breast cancer (BC) development in dogs has been studied, very little is known about the role of prolactin (PRL). New studies show that until recently, the importance of PRL in human BC development and progression has been highly underestimated. PRL plays a role in promoting benign as well as malignant neoplastic cell growth in BC in vitro and in vivo. Sporadic publications proposed a tumour promotor role in the dog. The goal of this review is to summarize our knowledge about PRL and human BC as well as canine mammary tumourigenesis, and propose future research in this area.  相似文献   

18.
  相似文献   

19.
Klotho is an anti-ageing gene and is known to act as a tumour suppressor in human hepatocellular carcinoma (HCC). According to a previous study, Klotho is present in normal canine mammary glands, and down-expression in tumours is positively associated with negative prognosis. However, the presence and significance of Klotho in canine HCC has not yet been reported. This study aimed to confirm Klotho expression in normal canine liver tissues using western blotting and immunohistochemistry, and whether the expression differed in non-neoplastic liver disease and HCC. Furthermore, correlation between clinicopathologic features and expression of Klotho was evaluated. All of the normal liver tissues showed the presence of Klotho, and Klotho expression was significantly decreased in the HCC tissue as compared to the non-neoplastic hepatic tissue. Additionally, Klotho expression was significantly associated with tumour size (P = .045), liver enzyme (alanine aminotransferase (ALT)) (P = .018), and metastasis (P = .024). Analysis of the survival curve revealed that reduced Klotho expression was significantly associated with poor disease-free survival (P = .041) in HCC. These results show that Klotho expression is present in normal canine liver tissue and that reduced Klotho expression is associated with poor prognosis in canine HCC. Thus, Klotho was presumed to be a potential clinical prognostic marker for canine HCC.  相似文献   

20.
COX‐2 expression affects mammary tumourigenesis by promoting angiogenesis and cell proliferation, encouraging metastatic spread and tumour‐associated inflammation. Samples of canine mammary tumours (n = 109) were submitted to immunohistochemistry to detect COX‐2, CD31, VEGF, Ki‐67, CD3 and MAC387 expression. Concurrent high expression of COX‐2/CD31, COX‐2/VEGF, COX‐2/Ki‐67, COX‐2/CD3 and COX‐2/MAC was associated with elevated grade of malignancy, presence of intravascular emboli and presence of lymph node metastasis. Tumours with high COX‐2 (P < 0.001) and tumours with concurrent expression of high COX‐2 and high CD31 (P = 0.008); high VEGF (P < 0.001); high Ki‐67 (P < 0.001); high CD3+ T‐lymphocytes (P = 0.002) and elevated MAC387 macrophages (P = 0.024) were associated with shorter overall survival (OS) time. Interestingly the groups with high COX‐2/CD31 and high COX‐2/VEGF retained their significance after multivariate analysis arising as independent predictors of OS. Present data highlight the importance of COX‐2 in canine mammary tumourigenesis.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号