• BMB Reports
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• v.53 no.12
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• pp.664-669
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• 2020

Breast cancer is one of the most frequently diagnosed cancers. Although biomarkers are continuously being discovered, few specific markers, rather than classification markers, representing the aggressiveness and invasiveness of breast cancer are known. In this study, we used samples from canine mammary tumors in a comparative approach. We subjected 36 fractions of both canine normal and mammary tumor plasmas to high-performance quantitative proteomics analysis. Among the identified proteins, LCAT was selectively expressed in mixed tumor samples. With further MRM and Western blot validation, we discovered that the LCAT protein is an indicator of aggressive mammary tumors, an advanced stage of cancer, possibly highly metastatic. Interestingly, we also found that LCAT is overexpressed in high-grade and lymph-node-positive breast cancer in silico data. We also demonstrated that LCAT is highly expressed in the sera of advanced-stage human breast cancers within the same classification. In conclusion, we identified a possible common plasma protein biomarker, LCAT, that is highly expressed in aggressive human breast cancer and canine mammary tumor.

• Journal of Veterinary Clinics
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• v.40 no.6
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• pp.445-451
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• 2023

An 8-year-old female pet rabbit presented at the veterinary clinic for mammary gland palpation due to the presence of a mass. Upon physical examination, a mass was identified in the left fourth mammary gland. Abdominal ultrasonography revealed a 3 × 2 cm mass in the right uterus and general thickening of the endometrium, suggesting uterine sinusitis. Multiple pulmonary nodules suspected to be metastatic lesions were identified on chest radiography. Surgery was performed to mastectomy and ovariohysterectomy (OHE). The histopathological examination of the tumor revealed mammary gland adenocarcinoma (simple-type) with multiple nodules consisting of the proliferation of tumor cells forming tubules containing secretory materials, cellular debris, and solid nests with a central area of necrosis. Metronomic chemotherapy was performed with cyclophosphamide and lomustine (CCNU) based on the histopathological findings. The quality of life has been well maintained, with no specific clinical symptoms observed for 8 months after metronomic chemotherapy. To the best of authors' knowledge, this study is the first to examine the effects of metronomic chemotherapy with cyclophosphamide and lomustine in a pet rabbit.

• Development and Reproduction
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• v.5 no.2
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• pp.175-180
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• 2001

The ectopic expression of gonadotropin releasing hormone(GnRH and luteinizing hormone(LH) in several tissues is a quite intriguing phenomenon. Recently, the presence of GnRH and its receptor has been clearly demonstrated in rodents and human mammary gland. In this context, one can postulate that the presence of local circuit composed of GnRH and LH in the gland. The present study was undertaken to elucidate whether there is a correlation between the LH expression in rat mammary gland and physiological status during the process of mammary differentiation. LH contents in mammary gland from cycling to weaning rats were measured by radioimmunoassay(RIA). In cycling rats, changes of the LH level in both serum and mammary gland showed similar pattern as the highest level in proestrus and the lowest level in diestrus II stage. While the serum LH levels were fluctuated from pregnant through involution stage, a sharp decline of mammary LH contents was observed in the lactating rats. This decrement was recovered in involuting rats to the level of proestrus stage. Reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot analyses demonstrated that the transcriptional activities of the mammary LH and GnRH were increased from diestrus I stage to estrus stage, and the increased levels were maintained in pregnant, lactation and involution stages. To test the hypothesis that the alteration in mammary LH expression might be steroid-dependant, ovariectomy(OVX) and steroid supplement model was employed. As expected, supplement of estradiol(E$_2$) after OVX remarkably decreased serum LH level compared to that in serum from vehicle-only treated rats. Likewise, administration of E$_2$ significantly reduced the mammary LH content. The present study demonstrated that (i) the LH expression in mammary gland could be altered by some physiological parameters such as estrous cycle, pregnancy, lactation and involution, and (ii) ovarian steroid especially estrogen seems to be one of major endocrine factors which are responsible for regulation of mammary LH expression.

• The Journal of Korean Medicine
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• v.34 no.2
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• pp.29-40
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• 2013

Objectives: To investigate therapeutic mechanisms of Gyejibokryeong-hwan (GJBRH) against gynaecological diseases, articles on biological assay were gathered and analyzed. Methods: The articles were classified as being from domestic or international journals, and by their year of publication. The mechanisms of the biological effects against gynaecological diseases were noted. Results: Of the 14 articles analyzed, 13 were published in China and 1 was from Japan. GJBRH showed therapeutic effect against uterine and mammary gland diseases. Uterine-related diseases such as endometriosis, hysteromyoma, adenomyosis, cancer, and inflammation can be improved by the administration of GJBRH through anti-angiogenesis, anti-inflammation, the modulation of immune cell and immunoglobulin, and the regulation of hormone secretion. GJBRH also reduced mammary hyperplasia by regulating hormone and cytokine release. Conclusions: We speculate that the inhibitory effect against uterine and mammary gland diseases could be related to the therapeutic efficacy of GJBRH in improving gynaecological diseases.

• Proceedings of the Korean Society of Veterinary Pathology Conference
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• 2003.10a
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• pp.40-40
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• 2003

The c-erbB2/neu oncogene (alias HER2, NEU) encoding a tyrosine kinase receptor protein, the overexpression of which correlates with a more rapid progression and a worse prognosis in human breast cancer [1]. Otherwise, this gene is still poorly investigated in veterinary oncology [2,3]. To gain insight into the patterns of c-erbB2/neu status in canine mammary tumor, we constructed one such mammary tumor tissue microarray (TMA) from 60 tumors from our lab. This enabled the amplification of c-erbB2/neu oncogene of all 60 tumors to be simultaneously analyzed by chromogenic in situ hybridization (CISH). The aim of this study was to evaluate status of c-erbB2/neu oncogene in canine mammary tumors and to correlate this status with the differentiation grade of neoplasm. (omitted)

• Korean Journal of Veterinary Research
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• v.28 no.2
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• pp.241-249
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• 1988

In order to investigate the morphological characteristics of dendritic cells in the mammary gland of the mouse (C57 BL/6), rat(W), rabbit and cat, the fine structures of the dendritic cells have been observed by the electron microscope. The results obtained were summarized as follows: The dendritic cells with the well-developed processes had an irregular shape, and lacked the desmosome. The pinocytotic vesicles and tubular invaginations of the cell membrane were frequently observed, and the mitochondria with the well-developed cristae were located in the restricted region in the cytoplasm of the dendritic cells. The nuclei of dendritic cells were indented, In the mice and rats, the dendritic cells had a few Langerhans cell granules(Birbeck granules). From the above results, it is confirmed that the ATPase-positive dendritic cells in the mammary gland are the Langerhans cells.

• Journal of Dairy Science and Biotechnology
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• v.37 no.1
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• pp.15-26
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• 2019

A common belief is that human milk is sterile. However, the development of culture-independent molecular methods, especially Next Generation Sequencing, has revealed that human milk harbors diverse and rich bacterial communities. Although studies aimed at characterizing the microbiota of human milk have produced different findings, Staphylococcus and Streptococcus are presumed to be normal members of the microbiota. Factors that influence variation in the microbiota are unclear; however, the postpartum time, route of delivery, maternal obesity, and health status may be influential. The origin of the microbiota is a hotly debated topic. Human milk bacteria are thought to be introduced through bacterial exposure of the mammary duct during breast feeding and/or the entero-mammary pathway from the maternal gastrointestinal tract. Although the exact mechanism related to the entero-mammary pathway is unknown, it is presumed that bacteria penetrate the intestinal epithelium and then migrate to the mammary gland, dendritic cells, and macrophages. In this review, various relevant studies are introduced.

• Proceedings of the KSAR Conference
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• 2001.03a
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• pp.59-59
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• 2001

Interleukin-10 (IL-10) is known as a regulator of inflammation and pathogenesis in mammalian organs, but its precise role is little known in the mammary gland. Our initial experiment showed that IL-10 expression levels in mice decreased at the lactation stage otherwise increased at the involution stage. To reveal the effects of IL-10 on the involution of mammary gland, expression profiles of the apoptosis-related genes were examined in transgenic mice expressing human IL-10 as well as in knock-out mice (IL-10-/-). Mild inflammatory legions by lymphocytes were observed in the mammary glands of transgenic lines at the lactation stage. The expression of TRAIL (Tumor necrosis factor-Related Apoptosis-Inducing Ligand) among the apoptosis-related genes was highly elevated in the transgenic mice while others were not significantly changed. Furthermore, TRAIL was down regulated by four fold in the IL-10-/- mice at the involution stage. The expression of DR4 was elevated at the involution stage of normal mice. DR4 was detected in the milk of transgenic mice but absent in that of normal mice. Our results proposed that the elevated IL-10 at the involution stage recruit lymphocytes and induce TRAIL and DR4 genes, therefore, lead to enter involution stage of mammary glands.

• Journal of Life Science
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• v.10 no.1
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• pp.22-36
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• 2000

The mammary gland contains a subpopulation of epithelial cells with large proliferative potentials which are the likely targets for carcinogens. These clonogenic cells can proliferate and differentiate into functional glandular structures. Multicellular secretory alveolar units (AU) develop from these clonogens in grafts of monodispersed rat mammary epithelial cells (RMEC) in gland-free mammary fat pads in intact recipient F344 rats co-grafted with mammotropic hormone-secreting pituitary tumors (MtT F4). Multicellular nonsecretory ductal units (DU) develop in grafts of monodispersed RMEC in gland-free fat pads in adrenalectomized recipient WF rats co-grafted with MtT W10. However, this effect were reversed by hydrocortisone replacement therapy. RMEC were isolated from appropriate donor rats as monodispersed mixed cells or, alternatively, RNA＋ cells were sorted by flow cytometry of mixed RMEC stained with FITC-RNA and PE-anti-Thy-1.1 monoclonal antibody. We grafted mixed or sorted PNA+ cells in gland-free mammary fat pads in recipient rats that were endocrinologically manipulated to induce AU or DU. Cells were also isolated from these AU or DU as mixed or sorted RNA＋ cells and sub-transplanted in recipient rats treated appropriately to induce AU or DU, respectively. Cells obtained from AU in grafts gave rise to clonal AU and from DU in grafts to DU on sub-transplantation in appropriate recipients. When adrenalectomized recipient WF rats co-grafted with MtT W10 received daily subcutaneous injections of hydrocortisone for periods of 21 days following the PHA＋ cell transplantation, AU, instead of DU, were developed. The histologies of these secondary AU and DU were not different from those of the primary AU and DU. Casein and laminin proteins were demonstrated by immunocytochemical staining of primary and secondary AU. Electron micrographs also demonstrated that AU were composed of secretory cells with milk protein in the cytoplasm. DU were composed of little or non-secretory ductal epithelial cells. These AU and DU also secreted large amounts of lipids. Clonogenic cells were more common in DU than in AU. Thus, AU and DU contain persistent subpopulations of clonogenic stem-like cells.

• International Journal of Stem Cells
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• v.9 no.2
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• pp.186-191
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• 2016

Background and Objectives: With the global demand for dairy protein for consumption growing annually, there has been increasing activity in the research field of dairy protein synthesis and production. From a manipulation perspective, it is more difficult to use live cattle for laboratory studies on the production of milk as well as of dairy protein such as casein, as compared with using laboratory animals like rodents. Therefore, we aimed to develop a mouse model of bovine mammary alveolar ducts for laboratory-scale studies. We studied the formation of the bovine mammary gland ductal structure by transplanting the MAC-T bovine alveolar cell line into mice. Methods and Results: MAC-T cells ($1{\times}10^7$) were suspended in Matrigel and injected into the dorsal tissue of 8-week-old male BALB/C nude mice. Histological analysis of tissue dissected from the MAC-T cell-transplanted mice after 6 weeks showed the typical morphology of the tubuloalveolar female gland, as well as glands made up of branching ducts that were surrounded by smooth muscle with small alveoli budding off the ducts. In addition, the epithelial markers CK14 and CK18 were expressed within the duct-like structure. Prolactin was detected in the duct interior in these CK14+ and CK18+ cells but not in the non-transplanted MAC-T cells. Conclusions: These results showed that duct-like tissue had been successfully formed after 6 weeks of transplantation of the CK14+ and CK18+ MAC-T cells into mice dorsal tissue. This mouse model will be a useful tool for further research on the bovine mammary gland.