• Title/Summary/Keyword: mammary

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In vitro evaluation of the antitumor activity of axitinib in canine mammary gland tumor cell lines

  • Hye-Gyu Lee;Ga-Hyun Lim;Ju-Hyun An;Su-Min Park;Kyoung-Won Seo;Hwa-Young Youn
    • Journal of Veterinary Science
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    • v.25 no.1
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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.

The cooperative regulatory effect of the miRNA-130 family on milk fat metabolism in dairy cows

  • Xiaofen Li;Yanni Wu;Xiaozhi Yang;Rui Gao;Qinyue Lu;Xiaoyang Lv;Zhi Chen
    • Animal Bioscience
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    • v.37 no.7
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    • pp.1289-1302
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    • 2024
  • Objective: There is a strong relationship between the content of beneficial fatty acids in milk and milk fat metabolic activity in the mammary gland. To improve milk quality, it is therefore necessary to study fatty acid metabolism in bovine mammary gland tissue. In adipose tissue, peroxisome proliferator-activated receptor gamma (PPARG), the core transcription factor, regulates the fatty acid metabolism gene network and determines fatty acid deposition. However, its regulatory effects on mammary gland fatty acid metabolism during lactation have rarely been reported. Methods: Transcriptome sequencing was performed during the prelactation period and the peak lactation period to examine mRNA expression. The significant upregulation of PPARG drew our attention and led us to conduct further research. Results: According to bioinformatics prediction, dual-luciferase reporter system detection, real-time quantitative reverse transcription polymerase chain reaction and Western blotting, miR-130a and miR-130b could directly target PPARG and inhibit its expression. Furthermore, triglyceride and oil red O staining proved that miR-130a and miR-130b inhibited milk fat metabolism in bovine mammary epithelial cells (BMECs), while PPARG promoted this metabolism. In addition, we also found that the coexpression of miR-130a and miR-130b significantly enhanced their ability to regulate milk fat metabolism. Conclusion: In conclusion, our findings indicated that miR-130a and miR-130b could target and repress PPARG and that they also have a functional superposition effect. miR-130a and miR-130b seem to synergistically regulate lipid catabolism via the control of PPARG in BMECs. In the long-term, these findings might be helpful in developing practical means to improve high-quality milk.

Mammary Performance of First Lactation Bali Cows (Bibos banteng) Fed Grass-Legume Based Diets in Relation to the Role of Glucose

  • Sukarini, I.A.M.;Sastradipradja, Djokowoerjo;Nusada, N.;Mahardika, I.G.;Kiranadi, B.
    • Asian-Australasian Journal of Animal Sciences
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    • v.14 no.5
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    • pp.615-623
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    • 2001
  • A study of mammary function in relation to glucose metabolism of first lactation Bali cows on grass-legume diets was carried out using 12 primiparous cows (initial BW $263.79{\pm}21.66kg$) for 16 weeks starting immediately post calving. The animals were randomly allocated into 4 dietary treatment groups R1, R2, R3 and R4, receiving from the last 2 months of pregnancy onwards, rations based on a mixture of locally available grass and legume feed ad libitum. On a DM basis R1 contained 70% elephant grass (PP, Penicetum purpureum) plus 30% Gliricidia sepia leaves (GS), R2 was 30% PP plus 25% GS supplemented with 55% Hibiscus tilliacius leaves (HT, defaunating effect), R3 and R4 were 22.5% PP+41.25% GS+11.25% HT+25% concentrate, with R4 supplemented with zinc-diacetate. TDN, CP and zinc contents of the diets were 58.2%, 12.05% and 18.3 mg/kg respectively for R1, 65.05%, 16.9% and 25.6 mg/kg respectively for R2, 66.03%, 16.71% and 29.02 mg/kg respectively for R3 and 66.03%, 16.71% and 60.47 mg/kg respectively for R4. Milk production and body weights were monitored, an energy and protein balance trial conducted, overall glucose kinetics parameters assessed, mammary blood flow (MBF) and metabolite arteriovenous differences (${\Delta}AVs$) measured to get uptake data and mammary performance relationships. Parameters of glucose kinetics at peak lactation or during dry condition were not affected by ration quality. Glucose pool size, space of distribution and flux increased by 61.77, 62.26 and 82.08%, respectively, during lactation compared to the dry period. Mean glucose flux of lactating Bali cows was $5.52mg/min.kgBW^{0.807}$ which resembles the range of values of temperate dairy cows. Calculation showed that glucose requirements for maintenance, milk lactose and fat-glycerol synthesis, and the formation of NADPH reached 461.69 g for a yield of 1 kg/d or equal to 320.62 mg/min, which was less than the average glucose flux of lactating Bali cows of 481.35 mg/min. Mammary blood flow (MBF) values ranged from 56 to 83 l/h for the different treatments and the ratio MBF per kg milk produced improved from av. 1540 l/kg for R1 to av. 967 l/kg for R4 treated cows. Mammary glucose uptake ranged from 6.27 to 12.03 g/h or 120 to 140 g/kg milk. Glucose uptake was mass-wise 2 to 4 times the amount secreted as lactose, which indicated values less than the calculated mammary glucose needs and that little lactose was synthesized. The excess glucose taken-up was used for other metabolic processes. Linear relationships between metabolite ${\Delta}AVs$ and arterial blood plasma concentration [A] showed that in Bali cows triglycerides (TG), phenylalanine (Phe) and tyrosine (Tyr) have high coefficients of determination, i.e. 0.77, 0.81 and 0.69, respectively. For glucose, the relationship is quadratic with an $R^2$ value of 0.49. It was concluded that lactose synthesis was inadequate, which led to a speculation that milk yield could be improved by increased lactose synthesis.

Immunity of the Buffalo Mammary Gland during Different Physiological Stages

  • Dang, A.K.;Kapila, Suman;Tomar, Parveen;Singh, Charan
    • Asian-Australasian Journal of Animal Sciences
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    • v.20 no.8
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    • pp.1174-1181
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    • 2007
  • To study the immunity of the buffalo mammary gland during involution and around parturition and compare it with the mastitic mammary gland, milk samples were collected from 9 Murrah buffaloes during the above critical periods. SCC of buffalo milk increased significantly (p<0.01) by day 21 of involution and one week prepartum. SCC was significantly higher around parturition but became normal at 14 days postpartum. Phagocytic activity (PA) and phagocytic index (PI) of the buffalo milk neutrophils decreased as the duration of the dry period increased. Elevated levels of immunoglobulins at calving improved the PA and PI, but the lowest PA of 18.8% and PI of 1.75 were recorded at 7 days postpartum. Buffaloes suffering from clinical mastitis had PA of 12.3% and PI of 1.46 that increased significantly (p<0.01) on the third day of treatment. Distance of teat from ground level was found to be minimum at one week before parturition. The investigation showed that in vitro phagocytic activity of buffalo neutrophils was weakest at one week postpartum.

Case Report of a Mammary Analogue Secretory Carcinoma of the Parotid Gland (이하선에서 발생한 유선 유사 분비성 암종의 증례보고)

  • Han, Sung Min;Park, Sang Man;Kwon, Hyeong Ju;Kim, Ji Hoon
    • Korean Journal of Head & Neck Oncology
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    • v.33 no.2
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    • pp.85-88
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    • 2017
  • Mammary analogue secretory carcinoma (MASC) is a rare malignant tumor of the salivary gland, which was first described in 2010. In this case report, we describe a 62-year-old woman with a MASC of the parotid gland, who initially presented with an asymptomatic preauricular mass. At first, computed tomography (CT) and fine needle aspiration cytology were performed; these suggested a possible Warthin's tumor but also some suspicious malignant findings. For the main treatment, adequate parotidectomy was conducted via modified Blair incision to remove the tumor. Postoperative pathology report revealed a MASC of the parotid gland. Specific MASC findings were observed upon immunohistochemical examination.

Expression of Human Lactoferrin in the Mammary Glands of Transgenic Mice using Regulatory Elements of Rat $\beta$-Casein Gene (흰쥐 베타-카제인 유전자의 발현조절 부위를 이용하여 유선에서 사람 락토페린을 발현하는 형질전환 생쥐의 개발)

  • 김선정;이고운;배수경;조용연;한용만;이철상;이경광;유대열
    • Korean Journal of Animal Reproduction
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    • v.18 no.2
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    • pp.133-139
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    • 1994
  • Two human lactoferrin expression vectors(pCChcLf and pCChcLf-1) were constructed using rat $\beta$-casein gene and human lactoferrin cDNA. The recombinant DNAs containing human lactoferrin cDNA were microinjected into the fertilized eggs of hybrid mice (BDF1 : C57BL$\times$DBA) and the DNA-injected eggs were treansferred into the oviducts of foster mothers. Genomic DNAs were isolated from the tails of mice born from the microinjected eggs and analyzed by Southern blot analysis. As a result, 5 and 9 transgenic mice with CChcLf and CChcLf-1 gene were produced, respectively. To determine tissue-specificity of transgene expression, Northern blot analysis was performed. Female transgenic mice were killed at day 10 of lactation and total RNAs from various tissues were isolated. Based on Northern blot analysis, it was shown that transgene was mainly expressed in the mammary glands of transgenic mice. In addition, the human lactoferrin in milk was detected by enzyme-linked immunosorbent assay. For this study, milk was obtained from the mammary glands of the transgenic mice at day 10 of lactation. In line #2 of CChcLf and line #7 of CChcLf-1 transgenic mice, human lactoferrin was secreted into the milk at concentration levels of 340ng/ml and 60ng/ml, respectively.

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Treatment of Malignant Melanoma by Downregulation of XIAP and Overexpression of TRAIL with a Conditionally Replicating Oncolytic Adenovirus

  • Li, Xin-Qiu;Ke, Xian-Zhu;Wang, Yu-Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1471-1476
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    • 2012
  • Background and Aim: Currently available systemic therapies for malignant melanoma produce low response rates in patients, and more effective treatment modalities are clearly needed. The tumor necrosis factor (TNF)-related apoptosis-inducing ligand has a significant impact on therapy for patients with X-linked inhibitor of apoptosis protein-downregulation malignant melanoma. The primary objective of this study was to assess its therapeutic potential. Materials and Methods: We employed a conditionally replicating oncolytic adenoviral vector, named CRAd5.TRAIL/siXIAP, with the characteristics of over-expression of the therapeutic gene TRAIL and downregulation of XIAP in one vector. B16F10-luc cells were employed to detect anti-tumor activity of CRAd5.TRAIL/siXIAP in vitro and in vivo. Results: CRAd5.TRAIL/siXIAP enhanced caspase-8 activation and caspase-3 maturation in B16F10 cells in vitro. Furthermore, it more effectively infected and killed melanoma cells in vitro and in vivo than other adenoviruses. Conclusion: Taken together, the combination of upregulation of TRAIL and downregulation of siXIAP with one oncolytic adenoviral vector holds promise for development of an effective therapy for melanomas and other common cancers.

Effect on Factors Related Lactation after Administration of Palmul-tang (팔물탕(八物湯) 복용이 산후 유즙분비 관련인자에 미치는 영향)

  • Song, Yun-Hui;Kim, Tae-Hee
    • The Journal of Korean Obstetrics and Gynecology
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    • v.23 no.1
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    • pp.12-29
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    • 2010
  • Purpose: This study was conducted to investigate the effect on factors related lactation after administration of Palmul-tang in postpartum C57BL/6N mice. Materials and Methods: Experimental groups were divided into control group post-par group and pre-par group. Pre-par and post-par group were administered Palmul-tang(p.o) twice a week for 4 weeks or 3 weeks respectively. Control group was administered normal saline for 3 weeks. Then we observed morphological change, immunohistochemical density and milk protein gene expression of factors related lactation within mammary gland of postpartum mice. Results: In post-par and pre-par groups, adipose tissue within mammary gland significantly decreased, and ductal branch and alveoli prominently developed than that of control group at 1~3 weeks after administraion of Palmul-tang. In post-par and pre-par groups, density of immunoreactivity on oxytocin, prolactin, estrogen and progesterone receptors in mammary glandular tissue significantly increased than that of control group. mRNA expression of $\beta$-casein and placental lactogen (PL)-1 in post-par group was more increased than that of control and pre-par groups. Conclusion: These results suggest that Palmul-tang significantly improved factors related lactation at postpartum period.

Effects of Controlled Compensatory Growth on Mammary Gland Development and Lactation in Rats

  • Moon, Yang S.;Park, Chung S.
    • Asian-Australasian Journal of Animal Sciences
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    • v.15 no.9
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    • pp.1364-1370
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    • 2002
  • The objective of this study was to examine the effect of compensatory growth nutritional regimen on mammary gland growth and lactation. One hundred twenty-two Sprague Dawley female rats (35 days of age) were randomly assigned to either a control or a stair-step compensatory nutrition (SSCN) feeding regimen or an alternating 2-2-3-3-week schedule beginning with 40% energy restriction for 2 weeks followed by re-alimentation (control diet) for 2 weeks. Pup weight gain and milk yield were improved 8% and 8 to 15%, respectively, by the SSCN regimen. The gene expression of $\beta$-casein was 2.3-fold greater in the SSCN group than in the control group during early lactation, but they were greater at all stages of the second lactation. The gene expression of insulin-like growth factor-I was 40% lower in the SSCN group than in the control group during early lactation of the second lactation, but during late lactation it was 80% greater than in the control group. The concentration of serum corticosterone tended to be higher in the SSCN group during the late stage of the first lactation. These results suggest that the stair-step compensatory nutrition regimen improves lactation performance and persistency by modulation of cell differentiation and apoptotic cell death.

Rapamycin Inhibits Expression of Elongation of Very-long-chain Fatty Acids 1 and Synthesis of Docosahexaenoic Acid in Bovine Mammary Epithelial Cells

  • Guo, Zhixin;Wang, Yanfeng;Feng, Xue;Bao, Chaogetu;He, Qiburi;Bao, Lili;Hao, Huifang;Wang, Zhigang
    • Asian-Australasian Journal of Animal Sciences
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    • v.29 no.11
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    • pp.1646-1652
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    • 2016
  • Mammalian target of rapamycin complex 1 (mTORC1) is a central regulator of cell growth and metabolism and is sufficient to induce specific metabolic processes, including de novo lipid biosynthesis. Elongation of very-long-chain fatty acids 1 (ELOVL1) is a ubiquitously expressed gene and the product of which was thought to be associated with elongation of carbon (C) chain in fatty acids. In the present study, we examined the effects of rapamycin, a specific inhibitor of mTORC1, on ELOVL1 expression and docosahexaenoic acid (DHA, C22:6 n-3) synthesis in bovine mammary epithelial cells (BMECs). We found that rapamycin decreased the relative abundance of ELOVL1 mRNA, ELOVL1 expression and the level of DHA in a time-dependent manner. These data indicate that ELOVL1 expression and DHA synthesis are regulated by mTORC1 in BMECs.