Lactogenesis in mammary gland is under the control of various lactogenic hormones including hypophysial growth hormone and prolactin. Recent studies reported that such pituitary lactogenic hormones are also expressed in mammary cells as well as in pituitary. For the purpose to analyze the role of these non-pituitary hormones in mammary cells, $\beta$ -lactoglobulin (BLG) gene promoter was selected as a model system. The growth hormone suppressed BLG promoter activity when it was applied alone on cultured mammary HCll cells. Along with lactogenic hormones such as insulin, prolactin and glucocorticoid, however, it significantly enhanced expression of BLG promoter activity in a dosage- dependent manner. Exogenous expression of the growth hormone gene in cultured mammary cells also strongly promoted cell proliferation and BLG promoter activity. Bovine growth hormone promoter, on the contrary, did not revealed any notable activity. Above results suggest that endogenous expression of the pituitary hormone genes in mammary cells is not a regulation leakage but a physiological control. Moreover, artificial overproduction of the growth hormone in mammary gland may help increase milk production.
Park, Ji-Sung;Jung, Ji-Youl;Jo, Suk Hee;Cheong, Jongtae;Kang, Tae-Young;Kim, Jae-Hoon
Korean Journal of Veterinary Research
/
v.48
no.3
/
pp.311-316
/
2008
A 7-year-old female Shih Tzu dog with lots of masses in the whole mammary gland was presented to the surgery department of the Veterinary Teaching Hospital in the Cheju National University. After surgical excision, all mammary samples were referred to Pathology Department of Veterinary Medicine. Grossly, masses were measuring up to $6.5{\times}4{\times}1cm$ and on cut surface of masses in right 1st, 3rd, 4th, 5th and left 1st, 3rd, 4th, 5th mammary masses were well delineated and firm, sulphur yellow, solid round to oval shape. Microscopically, most neoplastic sweat glands were severely proliferated in dermis and subcutis. Most tubules were lined by round to oval shaped epithelium with eosinophilic cytoplasm, hyperchromatic nuclei with high mitotic figures and severe central necrosis. The neoplastic epithelium also had PAS-positive diastase-resistant cytoplasmic granules, but negative with Perls iron stain. The left 2nd mass was well delineated, and had several dark brown areas and yellowish white glittered areas. Mass was well circumscribed with dense connective tissue. Neoplastic areas contained irregular sized mammary gland with papillary grown luminal epithelial cells in single or double cells layer with mitotic figures and small amounts of proliferated myoepithelial cells. Proliferated myoepithelial cells also produced slightly basophilic mucinous materials. Based on the gross, histopathologic and special staining characteristics, this dog was diagnosed as 90% of apocrine sweat gland aenocarcinoma and 10% mammary. complex adenomas in mammary masses. In our best knowledge, this is the first report for concurrent occurrence of apocrine sweat gland adenocarcinoma and mammary gland complex adenoma in mammary masses of the same dog.
This study was examined on the effect of ex-vivo immunotherapy in 7, 12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinogenesis. Sprague-Dawley female 40 rats were divided into Jour groups. As a positive control, Group I was intubated with DMBA, 5 mg /100 g body weight and single dose, at experimental onset. Group II was treated ex-vivo immunotherapy with polyinosinic-polycytidylic acid (Poly I : C) and Group III was treated with Interleukin-2 (IL-2). Group IV was negative control. All rats were sacrificed at 16 weeks after DMBA intubation. Mammary gland wet weight, dry fat free tissue weight, incidence of tumor, and the number of lobules, alveolar buds, terminal end buds, and terminal ducts were examined. Morphological changes of the mammary gland after treated with DMBA were analyzed by whole mount and histopathological method. As results, the induced mammary tumors of Group I, II and III were 60%, 33% and 0%, respectively. Histopathological types of induced-mammary tumors were adenoma, adenocarcinoma and carcinosarcoma. In analysis of the whole mount method, the number of the terminal end buds, terminal ducts and lobules were significantly lower in Group II (p<0.01) and III (p<0.01) than DMBA alone treated Group I. In microscopic observation, hyperplastic alveolar nodules were significantly lower in Group III than Group I (p<0.01). In conclusion, IL-2 had strong inhibitory effect on the mammary gland tumorigenesis induced by DMBA in rats. Whole mount method may be a useful technique to assess the mammary carcinogenesis. Moreover, hyperplastic alveolar nodules were very sensitive parameter to assess the mammary carcinogenesis.
The present study was carried out to observe the histopathological changes in the mammary gland of lactating rats and rabbits injected with dexamethasone. White rats were intramuscularly injected with 0.25mg, 0.5mg or 1.0mg of dexamethasone sodium phosphate (containing $9{\alpha}$-fluoro-$16{\alpha}$-methylprednisolone, 5.0mg/ml) daily for 3 to 10 days on the 3rd day after parturition and white rabbits were intramammary infused with 4mg or 20mg of dexamethasone daily for 4 days on 7th day after parturition. The histopathological changes of the mammary glands, ovaries and adrenal glands of rats and rabbits were observed with light microscope. In the mammary glands of rats, the microscopic findings encountered were decrease of the milk in the alveolar lumina, necrosis and desquamation of epithelial cells, atrophy of alveoli, proliferation of fibroblasts and thickness of alveolar walls, destruction of alveoli, presence of fat droplets within the glandular epithelial cells, infiltration of mononuclear cells and proliferation of adipose tissue, which were relative to the dose and duration of injection. Especially, in the cases of the administration of large doses or long duration, there were severe fibrosis and focal necrosis of glandular tissue. In the mammary glands of rabbits, the morphological changes were similar to those findings in the rats. The milk in the alveolar lumina was decreased gradually according to the dose and duration of injection, while milk fat concentration regarded to increase. In the histological findings of ovaries, necrosis of granulosa cellos, vacuolization and necrosis of luteal cells, atrophy and necrotic foci in the corpora lutes were observed. In the adrenal glands, hyperemia, hemorrhage, vacuolization of adrenal cortical cells, necrotic foci and atrophy of adrenal cortex were observed.
Kim, Yong-baek;Seo, Il-bok;Kim, Jae-hoon;Bak, Eun-jung;Kim, Dae-yong;Han, Jeong-hee
Korean Journal of Veterinary Research
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v.37
no.4
/
pp.843-854
/
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.
Twenty-four Javanese thin-tail ewes (11, 9, and 4 ewes giving birth to 1, 2, and 3 lambs, respectively) with similar body weight and age at breeding were used to study serum progesterone concentrations during pregnancy, milk production during lactation, and mammary gland indices at the end of lactation (3 months postpartum). The results of the experiment showed that averages serum progesterone concentrations during pregnancy in the ewes giving birth to twin and triplet lambs were higher (p < 0.01) than those giving birth to a single lamb. Ewes giving birth to 3 lambs had higher (p < 0.01) mammary dry fat-free tissue (DFFT) (by 31 and 34%), DNA concentration (by 25 and 16%) and RNA concentration (by 29 and 16%) at the end of lactation than those giving birth to 1 and 2 lambs. There was no difference in mammary collagen, protein and glycogen concentrations at the end of lactation among litter sizes. Ewes giving birth to 3 lambs had higher (p < 0.01) total mammary DNA content (by 64 and 61%) and RNA content (by 69 and 53%) at the end of lactation than those giving birth to 1 and 2 lambs. There was no difference in total mammary collagen, protein and glycogen contents at the end of lactation among litter sizes. Even though ewes with higher litter size had numerically higher milk production, there was no significant difference in milk production per 4 h among litter sizes. The results of the experiment indicated that ewes having higher litter size had greater mammary cell number and synthetic activities at the end of lactation. The results suggested that ewes with higher progesterone concentrations and better developed mammary glands during pregnancy could maintain higher cell number and activities throughout lactation.
Background: The most common incident cancer and cause of cancer-related deaths in women is breast cancer. The Myc gene is upregulated in many cancer types including breast cancer, and it is considered as a potential anti-cancer drug target. The present study was conducted to evaluate the Myc (gene and protein) expression pattern in an experimental mammary tumour model in rats. Materials and Methods: Thirty six Sprague Dawley rats were divided into: Experimental group (26 animals), which received the chemical carcinogen N-methyl nitrosourea (MNU) and a control group (10 animals), which received vehicle only. c-Myc oncoprotein and its mRNA expression pattern were evaluated using immunohistochemistry (IHC) and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), respectively, in normal rat mammary tissue and mammary tumours. The rat glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene was used as internal control for semi-quantitative RT-PCR. Results: Histopathological examination of mammary tissues and tumours from MNU treated animals revealed the presence of premalignant lesions, benign tumours, in situ carcinomas and invasive carcinomas. Immunohistochemical evaluation of tumour tissues showed upregulation and heterogeneous cellular localization of c-Myc oncoprotein. The expression levels of c-Myc oncoprotein were significantly elevated (75-91%) in all the tumours. Semi-quantitative RT-PCR revealed increased expression of c-Myc mRNA in mammary tumours compared to normal mammary tissues. Conclusions: Further large-scale investigation study is needed to adopt this experimental rat mammary tumour model as an in vivo model to study anti-cancer strategies directed against Myc or its downstream partners at the transcriptional or post-transcriptional level.
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.
In order to observe the distribution of mast cell on the stages of the mammary carcinogenesis, the numerical changes of mast cells in the mammary tumor development in rats treated with DMBA and compound 48/80 have been investigated by the light microscope. The results observed were summarized as follows: The appearance of tumor were not observed during the whole experimental period in the rats of the control group received injection of sterile saline, but tumors appeared in 100% of the animals, the tumor induction time that represented the number of days elapsing between the 3rd DMBA administration until a first tumor became $10{\times}10mm$ in diameter was $42.5{\pm}4.7$ days and the mean number of tumor masses per rat was $3.4{\pm}1.2$ in the DMBA treated group. And the majority of the DMBA-induced mammary neoplasms were appeared cervical mammary gland and thoracic mammary gland. The histological findings of mammary carcinoma were recognized adenocarcinoma in the DMBA treated group. Mast cells were distributed within the adipose tissues and the interglandular connective tissue in the control, but found to be randomly dispersed within the tumor cell masses, in the connective tissues adjacent to the periphery of the tumor, the adipose tissues and the subcutaneous tissues contiguous to the region of tumor development in the DMBA treated group. Numerical alterations of mast cells were observed in the mammary tumors that separated into three major classes of tumors: hyperplasia, atypical hyperplasia and carcinoma. The number of mast cells were distributed in the connective tissues adjacent to the mammary gland was $45.3{\pm}3.4$ cells in the control group, but was $50.2{\pm}4.9$ cells, $126.7{\pm}10.5$ cells and $340.3{\pm}19.2$ cells according to each stages of mammary tumorigenesis in the DMBA treated group.
The renewed interest in the use of hyperthermia in cancer therapy is based on radiobiological and clinical evidence indicating that there may be significant thereapeutic advantages with the use of hyperthermia alone or combined with irradiation plus heat. Authors performed the experiment using the chemically induced mammary carcinoma of rats to observe the difference in temperature changes between tumor and normal tissue during heat, and to compare the response of the tumors to radiation alone and to radiation plus hyperthermia. The results were as follows 1. Temperature of tumors was significantly higher than in the normal tissue during heating and the difference was about $1.5^{\circ}C$. 2. $TCD_{50}$ in radiation alone and hyperthermia immediately following radiation was 1,282 rad and 795 rad, respectively and TER value was 1.81.
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