Mammary hyperplasia (MHP) is the most commonly encountered mammary disease in women at the child-bearing stage. Especially, atypical hyperplasia which belongs to the precancerous category, is the disease for class I prevention of breast cancer. Therefore, advancing the clinical efficacy of MHP treatment is of critical importance. Chinese medicine (CM) and drugs show a peculiar effect in this field; the clinical or experimental researches concerning MHP treatment by CM compounds or patent drugs have been increasing gradually in recent years, but the thinking paths and methods for establishing the MHP animal model are divergent. Particularly, the disease/CM syndrome conjugated model (D/S model) has rarely been studied. For this reason, the pathogenetic mechanism, the establishment of an animal disease model, as well as the thinking paths and methods for establishing the D/S model of MHP are discussed and summarized preliminarily in this paper by the authors. This could provide a new way of thinking and method for creating the MHP model in modern medicine.
Animals ; Disease Models, Animal ; Hyperplasia ; pathology ; Mammary Glands, Animal ; pathology ; Medicine, Chinese Traditional ; Syndrome

A fibroadenoma was diagnosed in the left udder of a 3-month-old female Chios lamb. No recurrence was observed after surgery. Grossly, the tumor had a whitishgray lobular appearance, and the lobules were interlaced with thin septa. Microscopically, the tumor was composed of proliferating fibroepithelial tissue, including differentiated ducts lined by whorls and interlacing bundles of abundant loose fibrovascular stroma. Immunohistochemistry revealed the ductal epithelium to be positive for pancytokeratin (AE1/AE3) and loose fibrovascular stroma was positive for vimentin and basal cells covering the ductal epithelium of alpha-smooth-muscle actin. Immunostaining for the estrogen and progesterone receptors was negative. A diagnosis of mammary fibroadenoma was made based on the histological and immunohistochemical findings.
Animals ; Female ; Fibroadenoma/pathology/*veterinary ; Keratins/metabolism ; Mammary Glands, Animal/*pathology ; Mammary Neoplasms, Animal/*pathology ; Sheep ; Sheep Diseases/*pathology ; Vimentin/metabolism

OBJECTIVETo research the effects of Guizhi Fuling capsule on sex hormones levels in blood serum and breast issue morphology of hyperplasia of mammary glands model rats.

METHODThe unpregnancy SD rat models of hyperplasia of mammary glands were established by injecting 0.5 mg x kg(-1) benzoate estradiol. After five weeks doses,the effects of Guizhi Fuling capsule 2.0, 1.0, 0.5 g x kg(-1) and Rupixiao tablet 0.5 g x kg(-1) on the changes of papilla diameter, height and breast issue morphology of the naimal models were explored, and sex hormones levels in blood serum were measured.

RESULTGuizhi Fuling capsule can inhibitnipple swell, improve breast tissue morphology pathological profiles of the animal models, and decrease oestradiol (E2) level and increase progesterone (P) level in blood serum.

CONCLUSIONThese results suggested that Guizhi Fuling capsule could, improve mammary gland pathological profiles. Regulating sex hormone levels may be its important mechanism for treatment of hyperplasia of mammary glands.

Animals ; Capsules ; Drugs, Chinese Herbal ; pharmacology ; Female ; Gonadal Steroid Hormones ; blood ; Hyperplasia ; Mammary Glands, Animal ; drug effects ; pathology ; Rats

The tissue distribution and cellular localization of viral antigens in three cattle with persistent bovine viral diarrhea virus (BVDV) infection was studied. In three cases, necropsy findings of oral ulcers, abmasal ulcers and necrosis of Peyer's patches were suspected have been caused by BVDV infection. Non-cytopathic BVDV was isolated from a tissue pool of liver, kidneys and spleen. Immunohistochemical detection of BVDV showed that BVDV antigens were detected in both epithelial and nonepithelial cells in all examined organs, including the gastrointestinal tract, liver, pancreas, lung, lymphatic organs (spleen, lymph nodes), adrenal gland, ovary, uterus, and the mammary gland. These findings support the hypothesis that animals with persistent BVDV infection spread BVDV through all routes, and that infertility in BVDV infection is associated with the infection of BVDV in the ovaries and uteri.
Adrenal Glands/pathology/virology ; Animals ; Antigens, Viral/*isolation & purification ; Bovine Virus Diarrhea-Mucosal Disease/pathology/physiopathology/*virology ; Cattle ; Diarrhea Viruses, Bovine Viral/immunology/*isolation & purification ; Digestive System/pathology/virology ; Female ; Immunohistochemistry/veterinary ; Infertility, Female/virology ; Kidney/pathology/virology ; Lung/pathology/virology ; Lymphatic System/pathology/virology ; Mammary Glands, Animal/virology ; Ovary/pathology/virology ; Uterus/pathology/virology

Interferon-γ (IFN-γ) has been used to control cancers in clinical treatment. However, an increasing number of reports have suggested that in some cases effectiveness declines after a long treatment period, the reason being unclear. We have reported previously that long-term IFN-γ treatment induces malignant transformation of healthy lactating bovine mammary epithelial cells (BMECs) in vitro. In this study, we investigated the mechanisms underlying the malignant proliferation of BMECs under IFN-γ treatment. The primary BMECs used in this study were stimulated by IFN-γ (10 ng/mL) for a long term to promote malignancy. We observed that IFN-γ could promote malignant cell proliferation, increase the expression of cyclin D1/cyclin-dependent kinase 4 (CDK4), decrease the expression of p21, and upregulate the expression of cellular-abelsongene (c-Abl) and histone deacetylase 2 (HDAC2). The HDAC2 inhibitor, valproate (VPA) and the c-Abl inhibitor, imatinib, lowered the expression level of cyclin D1/CDK4, and increased the expression level of p21, leading to an inhibitory effect on IFN-γ-induced malignant cell growth. When c-Abl was downregulated, the HDAC2 level was also decreased by promoted proteasome degradation. These data suggest that IFN-γ promotes the growth of malignant BMECs through the c-Abl/HDAC2 signaling pathway. Our findings suggest that long-term application of IFN-γ may be closely associated with the promotion of cell growth and even the carcinogenesis of breast cancer.
Animals ; Carcinogenesis/pathology* ; Cattle ; Cell Cycle Proteins/metabolism* ; Cell Proliferation/drug effects* ; Cell Transformation, Neoplastic/pathology* ; Cells, Cultured ; Epithelial Cells/pathology* ; Female ; Histone Deacetylase 2/metabolism* ; Imatinib Mesylate/pharmacology* ; Interferon-gamma/pharmacology* ; Mammary Glands, Animal/pathology* ; Mammary Neoplasms, Experimental/pathology* ; Proto-Oncogene Proteins c-abl/metabolism* ; Signal Transduction ; Valproic Acid/pharmacology*

During normal postnatal mammary gland development and adult remodeling related to the menstrual cycle, pregnancy, and lactation, ovarian hormones and peptide growth factors contribute to the delineation of a definite epithelial cell identity. This identity is maintained during cell replication in a heritable but DNA-independent manner. The preservation of cell identity is fundamental, especially when cells must undergo changes in response to intrinsic and extrinsic signals. The maintenance proteins, which are required for cell identity preservation, act epigenetically by regulating gene expression through DNA methylation, histone modification, and chromatin remodeling. Among the maintenance proteins, the Trithorax (TrxG) and Polycomb (PcG) group proteins are the best characterized. In this review, we summarize the structures and activities of the TrxG and PcG complexes and describe their pivotal roles in nuclear estrogen receptor activity. In addition, we provide evidence that perturbations in these epigenetic regulators are involved in disrupting epithelial cell identity, mammary gland remodeling, and breast cancer initiation.
Animals ; Breast Neoplasms ; genetics ; pathology ; physiopathology ; Cell Transformation, Neoplastic ; Chromatin ; genetics ; metabolism ; Epigenesis, Genetic ; physiology ; Epithelial Cells ; cytology ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Histone-Lysine N-Methyltransferase ; Humans ; Mammary Glands, Animal ; cytology ; growth & development ; Mammary Glands, Human ; cytology ; growth & development ; Myeloid-Lymphoid Leukemia Protein ; genetics ; physiology ; Polycomb-Group Proteins ; genetics ; physiology ; Receptors, Estrogen ; metabolism

Cows infected with Escherichia (E.) coli usually experience severe clinical symptoms, including damage to mammary tissues, reduced milk yield, and altered milk composition. In order to investigate the host response to E. coli infection and discover novel markers for mastitis treatment, mammary tissue samples were collected from healthy cows and bovines with naturally occurring severe E. coli mastitis. Changes of mammary tissue proteins were examined using two-dimensional gel electrophoresis and label-free proteomic approaches. A total of 95 differentially expressed proteins were identified. Of these, 56 proteins were categorized according to molecular function, cellular component, and biological processes. The most frequent biological processes influenced by the proteins were response to stress, transport, and establishment of localization. Furthermore, a network analysis of the proteins with altered expression in mammary tissues demonstrated that these factors are predominantly involved with binding and structural molecule activities. Vimentin and alpha-enolase were central "functional hubs" in the network. Based on results from the present study, disease-induced alterations of protein expression in mammary glands and potential markers for the effective treatment of E. coli mastitis were identified. These data have also helped elucidate defense mechanisms that protect the mammary glands and promote the pathogenesis of E. coli mastitis.
Animals ; Cattle ; Electrophoresis, Gel, Two-Dimensional/veterinary ; Escherichia coli/*physiology ; Escherichia coli Infections/genetics/immunology/microbiology/*veterinary ; Female ; Mammary Glands, Animal/*immunology/pathology ; Mastitis, Bovine/*genetics/immunology/microbiology ; Proteome/*genetics/metabolism ; *Proteomics

OBJECTIVETo observe the effect of Ruxian Pill I (RXP I) on mammary gland hyperplasia (MGH) in rabbits and to explore its mechanism.

METHODSSixty rabbits were divided into the high, medium and low dose of RXP I groups, the Xiaoyao Pill (XYP) group, the model group and the normal control group with 10 in each group. The former 5 groups were injected with diethylstilbestrol and progesterone intramuscularly for one month to induce the MGH model and then given respective medicines via gastrogavage for 3 months. The changes in morphology of mammary gland were observed using light and electronic microscope, the levels of estradiol (E2) and progestogen (P) were measured by radioimmunoassay, and the expression of estradiol receptor (ER) and progestogen receptor (PR) were detected with immunohistochemistry before, at the end of and 3 months after the treatment.

RESULTSCompared with those before treatment and those in the model group, in the high and midium dose of RXP I groups after treatment, obvious decrease of acini number in hyper-plastic lobuli mammae, connective tissues and blood capillaries, layers of glandular epithelium cells and organellers were seen with partial of hyperplastic cell apoptosis in them. Besides, the serum E2 level decreased obviously (P < 0.05), while the serum P level increased, and the ER expression down-regulated significantly (P < 0.05), but no obvious changes of PR expression was found. Three months later, all the above indexes maintained stable without rebound.

CONCLUSIONRXP I treatment could alleviate the hyperplasia of mammary glands, reduce E2 level, and down-regulate ER expression in rabbits with MGH, showing a significant therapeutical effect.

Animals ; Diethylstilbestrol ; Drugs, Chinese Herbal ; therapeutic use ; Estradiol ; blood ; Female ; Hyperplasia ; blood ; chemically induced ; prevention & control ; Immunohistochemistry ; Mammary Glands, Animal ; drug effects ; metabolism ; pathology ; Phytotherapy ; Progesterone ; Progestins ; blood ; Rabbits ; Radioimmunoassay ; Receptors, Estradiol ; analysis

OBJECTIVETo study on the inhibitory action of combined acupuncture and medicine therapy on the model rat of hyperplasia of mammary glands and the mechanism.

METHODSThe model rat of hyperplasia of mammary glands were prepared. After modelling, they were randomly divided into an acupuncture group, a Chinese drug group and a combined acupuncture and drug group, a control group and a model group. Except both the control group and the model group, other 4 groups were treated respectively with acupuncture, Chinese drug, combined acupuncture and Chinese drug, and Premormine, once each day, 9 sessions constituting one course. After treatment of 3 courses (30 days), changes of the breast tissue form were observed, and the diameter and the area of the acina cavity were determined and expressions of estrogen receptor subgroups (ERalpha and ERbeta) were detected with immunohistochamical methods.

RESULTSThe diameter and the area of the acina cavity were increased in the model group as compared with those in the normal group (both P < 0.01), and in the treatment group they were decreased as compared with those in the model group (P < 0.05 or P < 0.01)); both acupuncture and Chinese drug could up-regulate the expression of ERbeta and down-regulate the expression of ERalpha.

CONCLUSIONBoth acupuncture and moxibustion, and Chinese medicine have inhibitory action on hyperplasia of mammary glands in the rat, with the strongest inhibitory action of the combined acupuncture and medicine treatment which is basically close to the level of Premormine. The mechanism is possily related with the up-regulation of ERbeta expression and down-regulation of ERalpha expression.

Acupuncture Points ; Acupuncture Therapy ; Animals ; Combined Modality Therapy ; Estrogen Receptor alpha ; analysis ; Estrogen Receptor beta ; analysis ; Female ; Hyperplasia ; Mammary Glands, Animal ; chemistry ; drug effects ; pathology ; Medicine, Chinese Traditional ; Rats ; Rats, Wistar

OBJECTIVETo study galactagogue effect of Maidang Rutong granule on the lactation rats.

METHODThe experiments were designed to observe the efficiency of Maidang Rutong granule on lactescence, serum prolactin, and morphology of mammary gland with rat galactozemia model established by injecting l-dopa.

RESULTMaidang Rutong granule showed significant enhancement for lactescence and the offspring's body weight. It could antagonize the decrease of serum prolactin and the atrophy of mammary gland induced by l-dopa.

CONCLUSIONMaidang Rutong granule exhibited significant galactagogue effect on the l-dopa-induced galactozemia in rats.

Animals ; Animals, Newborn ; Atrophy ; Body Weight ; drug effects ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; Female ; Lactation ; drug effects ; Lactation Disorders ; blood ; chemically induced ; physiopathology ; Levodopa ; Male ; Mammary Glands, Animal ; drug effects ; pathology ; Prolactin ; blood ; Random Allocation ; Rats ; Rats, Sprague-Dawley