Is There a Malignant Progression Associated with a Linear Change in Protein Expression Levels from Normal Canine Mammary Gland to Metastatic Mammary Tumors?

2011 ◽  
Vol 10 (10) ◽  
pp. 4405-4415 ◽  
Author(s):  
Patricia Klose ◽  
Christoph Weise ◽  
Angelika Bondzio ◽  
Gerd Multhaup ◽  
Ralf Einspanier ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Protein Expression ◽  
Mammary Tumors ◽  
Malignant Progression ◽  
Linear Change ◽  
Expression Levels ◽  
Canine Mammary Gland

scholarly journals Proinflammatory and Anti-Inflammatory Cytokines Mediated by NF-κB Factor as Prognostic Markers in Mammary Tumors

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Gustavo Rodrigues Martins ◽  
Gabriela Bottaro Gelaleti ◽  
Marina Gobbe Moschetta ◽  
Larissa Bazela Maschio-Signorini ◽  
Debora Ap. Pires de Campos Zuccari
Keyword(s):  
Protein Expression ◽  
Survival Time ◽  
Inflammatory Cytokines ◽  
Prognostic Markers ◽  
Tumor Development ◽  
Mammary Tumors ◽  
Clinicopathological Characteristics ◽  
Expression Levels ◽  
Gene And Protein Expression ◽  
High Gene

Inflammation results in the production of cytokines, such as interleukin- (IL-) 4 and IL-10 with immunosuppressive properties or IL-6 and TNF-αwith procarcinogenic activity. Furthermore, NF-κB is the major link between inflammation and tumorigenesis. This study verified the interaction between active inflammatory cytokines in the tumor microenvironment and serum of female dogs with mammary tumors and their correlation with the clinicopathological characteristics and overall survival. Measurement of gene expression was performed by qPCR and protein levels by ELISA/Luminex. High gene and protein expression levels of NF-κB, IL-6, and TNF-αwere found in association with characteristics that reflect worse prognosis and a negative correlation between TNF-αprotein expression and survival time was observed (p<0.05). In contrast, high gene and protein expression levels of IL-4 and IL-10 were associated with characteristics of better prognosis and an increased level of IL-4 and a longer survival time of animals were obtained (p<0.05). In addition, there was a positive correlation between TNF-αand IL-6 expression in association with NF-κB. The results show a significant correlation of these cytokines with tumor development, associated with NF-κB expression and cytokines promodulation, showing that these biological factors could be used as predictive and prognostic markers in breast cancer.

scholarly journals Expression of Bone Morphogenetic Protein-6 (BMP-6) in Myoepithelial Cells in Canine Mammary Gland Tumors

2001 ◽  
Vol 38 (6) ◽  
pp. 703-709 ◽  
Author(s):  
S. Tateyama ◽  
K. Uchida ◽  
T. Hidaka ◽  
M. Hirao ◽  
R. Yamaguchi
Keyword(s):  
Mammary Gland ◽  
Basement Membrane ◽  
Bone Morphogenetic Protein ◽  
Mammary Tumors ◽  
Myoepithelial Cells ◽  
Cytokeratin 19 ◽  
Mammary Gland Tumors ◽  
Morphogenetic Protein ◽  
Canine Mammary Gland ◽  
Mixed Tumors

Seventy-three mammary tumors and three mammary tissue specimens were examined to elucidate the expression of bone morphogenetic protein (BMP)-6 in the myoepithelial cells of canine mammary gland tumors. Morphologically, the myoepithelial cells were classified into four types: resting and proliferating cells inside the basement membrane, and spindle- and star-shaped cells proliferating in the outer area of the basement membrane. The characteristics of these myoepithelial cells were confirmed by immunohistochemistry using antibodies raised against keratin, cytokeratin 19, alpha-smooth muscle actin, and vimentin. In simple adenoma, a small number of resting myoepithelial cells was immunopositive for BMP-6. In complex adenomas and benign mixed tumors, all types of myoepithelial cells, depending in some cases on their specific location within the tumor, were immunopositive for BMP-6, but almost all of the tubular epithelial cells were immunonegative. Foci consisting of a proliferation of BMP-6–positive star- and spindle-shaped cells had mucinous stroma with marked hyaline and chondroid changes. In contrast, the foci with BMP-6–negative spindle- and star-shaped cells tended to have mucinous stroma without chondroid change. Several types of mesenchymal cells including chondrocytes, osteoblasts, and fibroblastlike cells in the mixed tumors, showed an intense immunopositive reaction for the BMP-6 antibody, and were located close to the ectopic cartilage and bone matrix. No significant immunoreactivity for BMP-6 was observed in most of the malignant mammary tumors; only one malignant mixed tumor was examined. All of these findings indicate that BMP-6 expression in myoepithelial cells may increase in complex adenomas and benign mixed tumors in canine mammary glands, and that BMP-6 expression is most intense in the vicinity of chondroid matrix in these tumors.

Cyclopedic protein expression analysis of cultured canine mammary gland adenocarcinoma cells from six tumours

2006 ◽  
Vol 80 (3) ◽  
pp. 317-323 ◽  
Author(s):  
T. Nakagawa ◽  
M. Watanabe ◽  
E. Ohashi ◽  
R. Uyama ◽  
S. Takauji ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Protein Expression ◽  
Expression Analysis ◽  
Adenocarcinoma Cells ◽  
Canine Mammary Gland

Relationship between receptors for insulin-like growth factor - I, steroid hormones and apoptosis-associated proteins in canine mammary tumors

2011 ◽  
Vol 14 (2) ◽  
pp. 245-251 ◽  
Author(s):  
I. Dolka ◽  
T. Motyl ◽  
E. Malicka ◽  
R. Sapierzyński ◽  
M. Fabisiak
Keyword(s):  
Mammary Gland ◽  
Growth Factor ◽  
Mammary Tumors ◽  
Insulin Like Growth Factor ◽  
Histologic Type ◽  
Factor I ◽  
Mammary Gland Tumors ◽  
Canine Mammary Tumors ◽  
Associated Proteins ◽  
Canine Mammary Gland

Relationship between receptors for insulin-like growth factor - I, steroid hormones and apoptosis-associated proteins in canine mammary tumors In the veterinary literature there are few data concerning the expression of insulin-like growth factor type I (IGF-IR) in the canine mammary gland tumors. The aim of the present study was the evaluation of IGF-IR expression and its correlation to the expression of estrogen receptor α (ERα) and progesterone receptor (PR), proteins: Bcl-2, Bax, p53 in canine mammary gland tumors, and also a correlation with other features: bitch's age, tumor diameter, histologic type of tumor, degree of histologic malignancy, proliferate activity. The study was done on 112 epithelial neoplasms: 21 (19%) were adenoma, 38 (34%) complex carcinoma (adenocarcinoma), 47 (42%) simple carcinoma (adenocarcinoma) and 6 (5%) solid carcinoma. Histochemistry and immunohistochemistry methods were employed. It was shown that more common and/or higher IGF-IR expression in cells of canine mammary gland tumors was related to the histologic type of cancer of worse prognostic (solid and simple carcinoma), high histologic degree of malignancy (III°) but the statistical analysis did not reveal any significant differences. We observed the high degree of IGF-IR expression in tumors which displayed the high ERα and PR expression. These results suggest the involvement of IGF-IR in the development of hormonosensitive canine mammary tumors. Additionally, the significant positive correlation between expression of IGF-IR and p53, Bax was found. Our study provides some evidence that interactions exist between the IGF-IR and these apoptosis-associated proteins may contribute to the development and progression of canine mammary gland tumors. These results require further investigations.

scholarly journals Sox4 Regulates the Sensitivity of Canine Mammary Gland Tumor Cells to Cisplatin via the Wnt/β-catenin Signaling Pathway

2021 ◽  
Author(s):  
Mengxin Hu ◽  
Siqi Huang ◽  
Enshuang Xu ◽  
Danning Tong ◽  
Shengzi Jin ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Cell Line ◽  
Signaling Pathway ◽  
Cisplatin Resistance ◽  
Epithelial Mesenchymal Transition ◽  
Mammary Gland Tumor ◽  
Gland Tumor ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Canine Mammary Gland

Abstract Background: The development of cisplatin resistance is one of the major causes of breast cancer treatment failure, and is associated with changes in Sox4 gene expression. In this study, a cisplatin-resistant cell line, CHMpCIS, was constructed from the cell line CHMp, which was isolated from the primary lesion of a malignant canine mammary gland tumor (CMGT). Sox4 expression was evaluated to assess its roles in cisplatin sensitivity, proliferation and apoptosis, epithelial-mesenchymal transition (EMT), cancer stem cell (CSC) features, and activation of the Wnt/β-catenin signaling pathway in CMGT cells.Results: CHMpCIS Cells exhibited changes in morphology, slower proliferation, and greater anti-apoptotic ability, EMT and CSC features, and the Wnt/β-catenin pathway was activated in CHMpCIS cells. In CMGT tissues, Sox4 expression was elevated. In CHMpCIS cells, silencing Sox4 inhibited cisplatin resistance, EMT and CSC features, and Wnt/β-catenin signaling activation. Then activating the Wnt/β-catenin signaling pathway increased Sox4 expression levels.Conclusions: Silencing Sox4 inhibited the above-mentioned cancer cell characteristics in CHMpCIS cells compared with CHMp cells. In addition, activating the Wnt/β-catenin signaling pathway increased Sox4 expression levels, as part of a positive feedback loop. These findings may provide new targets and therapeutic strategies for the clinical treatment of CMGT as well as a reference for human mammary gland tumor (HMGT) research.

c-erbB2 receptor and P53 protein expression in canine mammary gland carcinoma

2011 ◽  
Vol 21 (6) ◽  
pp. 1633-1636 ◽  
Author(s):  
Annahita Rezaie ◽  
Abbas Tavasoli ◽  
Mitra Mehrazma ◽  
Alireza Bahonar
Keyword(s):  
Mammary Gland ◽  
Protein Expression ◽  
P53 Protein ◽  
P53 Protein Expression ◽  
Mammary Gland Carcinoma ◽  
Erbb2 Receptor ◽  
Gland Carcinoma ◽  
Canine Mammary Gland

scholarly journals Quantification of Global DNA Methylation in Canine Mammary Gland Tumors via Immunostaining of 5-Methylcytosine: Histopathological and Clinical Correlations

2021 ◽  
Vol 8 ◽  
Author(s):  
Luiz Roberto Biondi ◽  
Marcello Vannucci Tedardi ◽  
Luciana Boffoni Gentile ◽  
Patricia Pereira Costa Chamas ◽  
Maria Lucia Zaidan Dagli
Keyword(s):  
Dna Methylation ◽  
Mammary Gland ◽  
Mammary Tumor ◽  
Malignant Tumors ◽  
Large Diameter ◽  
Mammary Tumors ◽  
Global Dna Methylation ◽  
Mammary Gland Tumors ◽  
Clinical Correlations ◽  
Canine Mammary Gland

Mammary tumors are the most prevalent neoplasms in non-neutered female dogs, with genetic and epigenetic alterations contributing to canine mammary carcinogenesis. This study quantified global DNA methylation in 5-methylcytosine (5mC)-immunostained canine mammary tumor samples and established histopathological and clinical correlations. A total of 91 formalin-fixed paraffin-embedded mammary tumor samples from female dogs were retrospectively selected and subjected to immunohistochemistry using an anti-5mC mouse monoclonal antibody. We evaluated 5mC+ stained nuclei of neoplastic epithelial cells in canine mammary glands to obtain semiquantitative histoscores based on staining intensity. Survival rates were estimated based on owners' or veterinary records. Histological samples comprised 28 and 63 benign and malignant canine mammary gland tumors, respectively. Results revealed significant differences between global DNA methylation patterns when mammary samples were categorized as benign or malignant (p = 0.024), with hypomethylated patterns more prevalent in malignant tumors and those with higher relapse behavior (p = 0.011). Of note, large diameter (&gt;5 cm) tumors revealed a lower methylation pattern (p = 0.028). Additionally, we found non-statistically significant differences when tumors were grouped by histopathological characteristics, clinical parameters, or survival. These findings propose global DNA methylation assessment as a promising tool for detecting canine mammary tumors with relapse propensity.

scholarly journals Pirfenidone attenuates synovial fibrosis and postpones the progression of osteoarthritis by anti-fibrotic and anti-inflammatory properties in vivo and in vitro

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qilu Wei ◽  
Ning Kong ◽  
Xiaohui Liu ◽  
Run Tian ◽  
Ming Jiao ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay ◽  
Fast Green ◽  
Expression Levels ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Safranin O ◽  
Tgf Β1

Abstract Background Osteoarthritis (OA) is a disease of the entire joint involving synovial fibrosis and inflammation. Pathological changes to the synovium can accelerate the progression of OA. Pirfenidone (PFD) is a potent anti-fibrotic drug with additional anti-inflammatory properties. However, the influence of PFD on OA is unknown. Methods Proliferation of human fibroblast-like synoviocytes (FLSs) after treatment with TGF-β1 or PFD was evaluated using a Cell Counting Kit-8 assay and their migration using a Transwell assay. The expression of fibrosis-related genes (COL1A1, TIMP-1, and ACTA-2) and those related to inflammation (IL-6 and TNF-α) was quantified by real-time quantitative PCR. The protein expression levels of COL1A1, α-SMA (coded by ACTA-2), IL-6 and TNF-α were measured by enzyme-linked immunosorbent assay. A rabbit model of OA was established and then PFD was administered by gavage. The expression of genes related to fibrosis (COL1A1, TIMP-1, and ADAM-12) and inflammation (IL-6 and TNF-α) was measured using RNA extracted from the synovium. Synovial tissue was examined histologically after staining with H&E, Masson’s trichrome, and immunofluorescence. Synovitis scores, the volume fraction of collagen, and mean fluorescence intensity were calculated. Degeneration of articular cartilage was analyzed using a Safranin O-fast green stain and OARSI grading. Results The proliferation of FLSs was greatest when induced with 2.5 ng/ml TGF-β1 although it did not promote their migration. Therefore, 2.5 ng/ml TGF-β1 was used to stimulate the FLSs and evaluate the effects of PFD, which inhibited the migration of FLSs at concentrations as low as 1.0 mg/ml. PFD decreased the expression of COL1A1 while TGF-β1 increased both mRNA and protein expression levels of IL-6 but had no effect on α-SMA or TNF-α expression. PFD decreased mRNA expression levels of COL1A1, IL-6, and TNF-α in vivo. H&E staining and synovitis scores indicated that PFD reduced synovial inflammation, while Masson’s trichrome and immunofluorescence staining suggested that PFD decreased synovial fibrosis. Safranin O-Fast Green staining and the OARSI scores demonstrated that PFD delayed the progression of OA. Conclusions PFD attenuated synovial fibrosis and inflammation, and postponed the progression of osteoarthritis in a modified Hulth model of OA in rabbits, which was related to its anti-fibrotic and anti-inflammatory properties.

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