• 대한수의학회지
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• 제62권1호
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• pp.9.1-9.6
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• 2022

Canine mammary gland tumors are the most common neoplasms in intact female dogs. Approximately half of all mammary tumors are malignant, and there is a risk of metastasis, which is associated with a poor prognosis. This study was to evaluate the prognostic factors of canine mammary gland tumors and the risk factors associated with the development of malignant tumors. From 2014 to 2020, 60 dogs with mammary gland tumors that underwent surgical treatment were evaluated in this retrospective study. Tumor size, TNM stage, and histopathological results were prognostic factors for 2-year survival after surgery. Every 10 mm increase in tumor size, increased the risk of death within 2 years after surgery 1.213 times. Dogs with TNM stage IV or V had 8.667 fold risk of death within 2 years after surgery. The 2-year survival rate for dogs with benign tumors was 90.2% and for malignant tumors was 67.3%. Tumor size is the most important prognostic factor for canine mammary gland tumors. As tumor size increased by 10 mm, the risk for development of malignant tumors increased by 1.487 times. Tumors larger than 30 mm are highly likely to be malignant, and metastatic evaluation and wide resection should be considered.

• 대한수의학회지
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• 제37권4호
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• pp.843-854
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• 1997

Sixteen mammary gland tumors were collected from Seoul National University and Kangwon National University. The average age of the bitches with mammary gland tumor was 10 years. Total 17(60.7%) out of 28 tumor masses observed in 4th and 5th glands. Classification of these tumors according to Hampe and Misdorp were simple adenoma, complex adenoma, benign mixed tumor, papillary adenocarcinoma, solid adenocarcinoma and malignant mixed tumor. Immunohistochemical reaction of the intermediate filaments against normal canine mammary gland showed as followed; anti-cytokeratin 18 was strong and anti-cytokeratin 14 was moderate to the luminal epithelium. Anti-cytokeratin 14 and anti-pancytokeratin to the myoepithelium were showed strong, but anti-vimentin was weak in reactivity. Anti-vimentin to the interstitial cells was represented strong reactivity. The origin of cartilage in mixed tumor of canine mammary gland was studied immunohistochemically with antibodies against intermediate filament. In mammary gland mixed tumors, cartilage tumor tissues were surrounded with the irregularly demarcated three zones composed of adjacent star shaped cells in myxoid areas, proliferative spindle shaped cells and basal located proliferated cells. From basal proliferated cells to star shaped cells, the immunohistochemical reactivity of myoepithelium specific anti-pancytokeratin was decreased gradually and the reactivity of interstitial cell specific anti-vimentin was increased gradually. Based on these immunohistochemical staining patterns, we suggested that the origin of cartilagenous components in canine mammary gland mixed tumor is most likely to the proliferation and metaplsia of myoepithelium.

• 한국임상수의학회지
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• 제38권6호
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• pp.274-278
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• 2021

An 11-year-old, intact female, Miniature Poodle presented with an abdominal mass. The abdominal mass was located around the right fifth mammary gland. The surgically removed mammary mass was subjected to histopathological examination. Based on the microscopic interpretation, a final diagnosis of an intermediate grade infiltrative mammary comedocarcinoma was established. Computed tomography for metastasis evaluation after surgical resection of the tumor showed enlarged right medial iliac and right inguinal lymph nodes, and a micronodule in the accessory lung lobe, suggesting metastasis of the mammary gland tumor. Doxorubicin, a chemotherapeutic drug, was administered six times at three week intervals. However, despite chemotherapy, the masses around the fourth and fifth mammary gland on the right side enlarged in size, and the treatment was discontinued at the request of the owner. The anticancer response to mammary comedocarcinoma is poor and the patient is in hospice management. This is the first attempt to treat a case of canine mammary comedocarcinoma in South Korea.

• 한국수의병리학회:학술대회논문집
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• 한국수의병리학회 2003년도 추계학술대회초록집
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• pp.48-48
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• 2003

Mammary cancer is the most common malignant neoplasm in the bitch. It constitute 40 percent of all tumors in female dogs, which is three times higher than incidence of mammary tumors in humans[2]. Cytological differentiation between benign and malignant canine mammary tumors is difficult, however, an irregular chromatin pattern was reported to be a significant criterion for malignancy[1]. It can be estimated that approximately 30 percent of the surgically removed mammary tumors are malignant[4]. Malignant mammary tumors often have some degree of infiltrative/destructive growth into adjacent tissues and/or invasion of vessels. Malignant mammary tumors often metastasize into local lymph nodes and lungs, and less frequently into other organs[3]. Based on histological and cytological criteria, this case was diagnosed as tubulopapillary carcinoma of the mammary gland. (omitted)

• Journal of Veterinary Science
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• 제21권2호
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• pp.23.1-23.10
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• 2020

The identification of biomarkers that distinguish diseased from healthy individuals is of great interest in human and veterinary fields. In this research area, a metabolomic approach and its related statistical analyses can be useful for biomarker determination and allow non-invasive discrimination of healthy volunteers from breast cancer patients. In this study, we focused on the most common canine neoplasm, mammary gland tumor, and herein, we describe a simple method using ultra-high-performance liquid chromatography to determine the levels of tyrosine and its metabolites (epinephrine, 3,4-dihydroxy-L-phenylalanine, 3,4-dihydroxyphenylacetic acid, and vanillylmandelic acid), tryptophan and its metabolites (5-hydroxyindolacetic acid, indoxyl sulfate, serotonin, and kynurenic acid) in canine mammary cancer urine samples. Our results indicated significantly increased concentrations of three tryptophan metabolites, 5-hydroxyindolacetic acid (p < 0.001), serotonin, indoxyl sulfate (p < 0.01), and kynurenic acid (p < 0.05), and 2 tyrosine metabolites, 3,4-dihydroxy-L-phenylalanine (p < 0.001), and epinephrine (p < 0.05) in urine samples from the mammary gland tumor group compared to concentrations in urine samples from the healthy group. The results indicate that select urinary tyrosine and tryptophan metabolites may be useful as non-invasive diagnostic markers as well as in developing a therapeutic strategy for canine mammary gland tumors.

• 생명과학회지
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• 제31권2호
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• pp.248-255
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• 2021

유선종양은 암컷 개에서 가장 흔한 암 중의 하나이며 종양 타입에 따라 조직학적으로 다양한 종류의 세포들이 존재한다. 특히, 복합 상피암종(complex carcinoma)의 경우 내강상피세포(luminal epithelium)와 근상피세포(myoepithelium)가 혼재되어 종양 내 세포 이형성(intra-tumoral heterogeneity)을 보인다. 하지만, 이러한 다양한 종양세포의 기원과 종양의 악성화에 미치는 영향에 대해서는 아직 밝혀진 바 없다. 최근, 여러 종류의 사람 종양에서 알려진 종양줄기세포는 종양 내 세포의 다양성(diversity)에 관여하고 악성화에도 기여할 수 있다고 보고되었다. 흥미롭게도 종양줄기세포는 자가재생능과 다분화능을 갖는 정상줄기세포와 동일한 능력을 가지고 있지만 종양 특이 유전자의 돌연변이와 줄기세포성격유지를 조절하는 신호전달체계에 문제가 있어 종양의 발생 시작부터 다른 조직으로의 전이에 관여하여 개체의 생존률에 직접적인 영향을 준다. 뿐만 아니라, 방사선 및 화학항암제에 대한 저항성을 보이기 때문에 종양 재발에 밀접하게 연관되어 있다. 본 리뷰 논문은 개 유선종양의 특성 및 종류, 종양줄기세포의 정의, 분리 방법, 임상학적 중요성에 대해서 정리하였다.

• Journal of Veterinary Science
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• 제25권1호
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• pp.1.1-1.15
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• 2024

Background: Axitinib, a potent and selective inhibitor of vascular endothelial growth factor (VEGF) receptor (VEGFR) tyrosine kinase 1,2 and 3, is used in chemotherapy because it inhibits tumor angiogenesis by blocking the VEGF/VEGFR pathway. In veterinary medicine, attempts have been made to apply tyrosine kinase inhibitors with anti-angiogenic effects to tumor patients, but there are no studies on axitinib in canine mammary gland tumors (MGTs). Objectives: This study aimed to confirm the antitumor activity of axitinib in canine mammary gland cell lines. Methods: We treated canine MGT cell lines (CIPp and CIPm) with axitinib and conducted CCK, wound healing, apoptosis, and cell cycle assays. Additionally, we evaluated the expression levels of angiogenesis-associated factors, including VEGFs, PDGF-A, FGF-2, and TGF-β1, using quantitative real-time polymerase chain reaction. Furthermore, we collected canine peripheral blood mononuclear cells (PBMCs), activated them with concanavalin A (ConA) and lipopolysaccharide (LPS), and then treated them with axitinib to investigate changes in viability. Results: When axitinib was administered to CIPp and CIPm, cell viability significantly decreased at 24, 48, and 72 h (p < 0.001), and migration was markedly reduced (6 h, p < 0.05; 12 h, p < 0.005). The apoptosis rate significantly increased (p < 0.01), and the G2/M phase ratio showed a significant increase (p < 0.001). Additionally, there was no significant change in the viability of canine PBMCs treated with LPS and ConA. Conclusion: In this study, we confirmed the antitumor activity of axitinib against canine MGT cell lines. Accordingly, we suggest that axitinib can be applied as a new treatment for patients with canine MGTs.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6415-6421
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• 2012

Background: Canine mammary gland tumors (CMGTs) are the most common tumor found in bitches. Changes in HER-2/neu genes in human breast cancer (HBC) lead to decrease in disease-free survival (DFS) and overall survival rate (OSR). Previous studies have demonstrated that the biological behavior of malignant mammary gland tumors (MMGTs) is similar to that of HBC. The present study aimed at evaluating the relationship between overexpression of HER-2/neu and clinicopathological features in MMGTs to represent a model of prognostic factors for HBC. Materials and Method: The clinicopathological data of 35 MMGTs were obtained. Immunohistochemical staining with HER-2, Ki-67 and CD34 markers was conducted with sections from paraffin-embedded blocks. According to standard protocols, histological type, grade, margin status, lymphovascular invasion (LVI), HER-2/neu score, proliferation rate and microvessel density (MVD) of tumors were determined and the association of HER-2/neu overexpression with these parameters was assessed statistically. Results: The IHC results showed that 12 (34.3%) cases were HER-2/neu positive. Statistical analyses indicated a significant relationship between HER-2 positivity and tumor grade (p=0.043), which also was demonstrated with cancer stage (p=0.035), tumor margin involvement (p=0.016), proliferation index (p=0.001) and MVD (p=0.001); however, there was no statistical relationship between LVI and tumor size. Overexpression of the HER-2/neu gene in MMGTs results in similar biological behavior as that of HBC; as a result, these tumors have can be considered to have important similarities in clinicopathological characteristics. Conclusions: MMGTs can be regarded as an HBC animal model. Further studies in this field would result in new treatments that could be beneficial for both dogs and humans.

• 생명과학회지
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• 제34권6호
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• pp.434-441
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• 2024

유선 종양은 중성화되지 않은 암컷 반려견에서 가장 빈번하게 발견되는 종양으로, 중요한 임상 문제로 대두되고 있다. 반려견 유선 종양(CMT)과 인간 유방암(HBC)의 강한 유사성으로 인해, 인간 유방암에서 확인된 바이오 마커는 반려견 유선종양에서도 검출될 수 있다. 이러한 바이오 마커는 조기 진단, 예후 및 치료 전략에 유용한 통찰력을 제공하는 것으로 나타났다. 본 논문은 연구되어진 반려견 유선종양 바이오 마커에 대한 간략한 개요를 제공하고자 한다. 반려견 유선 종양의 전통적인 치료는 외과적 수술로 시작하여 화학요법, 방사선 요법, 또는 호르몬 요법이 뒤따르지만, 이러한 치료법만으로는 항상 충분하지 않을 수 있다. 반려견 유선 종양 특이적 발암 기전 이해의 바탕으로 개발된 바이오 마커는 환견에게 더 나은 결과를 제공할 희망을 준다. 단일 세포 RNA 시퀀싱 분석은 종양 내 및 종양 간 이질성에 대한 유익한 정보를 제공할 수 있다. 본 리뷰 논문은 반려견 유선 종양 바이오 마커에 대한 현재 연구를 탐구하고 그 발전 방향을 제안한다.

• 한국임상수의학회지
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• 제27권3호
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• pp.232-239
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• 2010

개에서 자연발생한 유선종양으로부터 채취, 배양된 세포주 2개를 확립하고 특성을 분석하였다. 9세 령의 퍼그 종 개와 동일연령의 토이푸들 종의 개에 발생한 종양을 무균 상태를 유지하여 수술적으로 채취한 후 primary culture를 실시하였다. 두 종양의 조직병리검사에서는 각각 선암종과 혼합암종이 진단되었으며, 이후 두 마리 모두 전이로 인해 폐사하였다. 배양된 종양세포는 1년 이상의 기간 동안 60회 이상 계대를 반복하면서 형태학적으로 일관성을 유지하였고, 특성분석을 위해 광학현미경검사, 성장곡선 산출, 배가 시간 계산, 누드 마우스에 이종이식, 면역조직 화학검사를 실시하였다. 각 세포주는 다각형의 긴 세포형태를 보였으며, 세포질 연결을 형성하였으며, 배가 시간은 각각 47.1 시간과 18.6 시간이었다. 암컷 누드마우스의 등 부위에 피하이식 후 4주 이내에 10마리 중 9마리에서 촉진이 가능한 종괴의 형성이 확인되었으며, 면역조직화학검사 시 한 세포주에서는 keratin과 cytokeratin 8에서 다른 세포주에서는 smooth muscle actin과 cytokeratin 8에서 강한 염색성이 확인되었다. 두 세포주는 개의 유선종양의 시험관내, 체내 연구에 있어 모두 유용하게 사용될 수 있을 것으로 생각된다.