Sample records for ultrasonography mammary

  1. B-mode and Doppler sonography of the mammary glands in dairy goats for mastitis diagnosis.

    PubMed

    Santos, Vjc; Simplício, K; Sanchez, D; Coutinho, L; Teixeira, P; Barros, F; Almeida, V; Rodrigues, L; Bartlewski, P; Oliveira, M; Feliciano, M; Vicente, W

    2015-04-01

    This study aimed to evaluate the sonographic characteristics of the udder and teats and to determine the Doppler indexes of mammary artery in healthy and undergoing subclinical and clinical mastitis goats. Thirty animals among Saanen and Alpine Brown goats were arranged in three groups, healthy goats (HG), goats with subclinical mastitis (SMG) and goats with clinical mastitis (CMG). Using the B-mode, the sonographic characteristics (echotexture and echogenicity) and biometry (diameter and area of the udder cistern, diameter and area of the teat cistern and thickness of the teat wall) were evaluated. Using Doppler ultrasonography, the vascular indexes of the mammary artery were obtained. It was observed hyperechogenicity with solid component in the gland cistern when comparing animals with clinical mastitis and healthy mammary tissue. Regarding the echotexture of the breast tissue, there was heterogeneity in the mammary parenchyma on the three groups, for the milk, it was observed homogeneity for animals on HG and SMG and heterogeneity for animals on CMG. Grey-scale quantitative assessment revealed increase in echogenicity (mean value) for all the structures when comparing the three groups. Biometry did not reveal statistical difference between groups, for none of the evaluated structures. Doppler examination of the mammary artery showed the decrease of end diastolic velocity and raise of pulsatility index between groups. The association of B-mode and Doppler ultrasonography is useful for the evaluation of the udder of dairy goats with mastitis. It is a sensitive and specific method for the study of this disease. Doppler mode was unable to establish reliable criteria for diagnosis of subclinical mastitis. Moreover, the quantification of echogenicity is a useful technique for the evaluation of the milk in animals with mastitis; therefore, it is suggested that it can be used as complementary technique for the diagnosis of mastitis in goats. © 2015 Blackwell Verlag

  2. Physiologically activated mammary fibroblasts promote postpartum mammary cancer

    PubMed Central

    Guo, Qiuchen; Burchard, Julja; Spellman, Paul

    2017-01-01

    Women diagnosed with breast cancer within 5 years of childbirth have poorer prognosis than nulliparous or pregnant women. Weaning-induced breast involution is implicated, as the collagen-rich, immunosuppressive microenvironment of the involuting mammary gland is tumor promotional in mice. To investigate the role of mammary fibroblasts, isolated mammary PDGFRα+ cells from nulliparous and postweaning mice were assessed for activation phenotype and protumorigenic function. Fibroblast activation during involution was evident by increased expression of fibrillar collagens, lysyl oxidase, Tgfb1, and Cxcl12 genes. The ability of mammary tumors to grow in an isogenic, orthotopic transplant model was increased when tumor cells were coinjected with involution-derived compared with nulliparous-derived mammary fibroblasts. Mammary tumors in the involution-fibroblast group had increased Ly6C+ monocytes at the tumor border, and decreased CD8+ T cell infiltration and tumor cell death. Ibuprofen treatment suppressed involution-fibroblast activation and tumor promotional capacity, concurrent with decreases in tumor Ly6C+ monocytes, and increases in intratumoral CD8+ T cell infiltration, granzyme levels, and tumor cell death. In total, our data identify a COX/prostaglandin E2 (PGE2)–dependent activated mammary fibroblast within the involuting mammary gland that displays protumorigenic, immunosuppressive activity, identifying fibroblasts as potential targets for the prevention and treatment of postpartum breast cancer. PMID:28352652

  3. Mammary stem cells: angels or demons in mammary gland?

    PubMed

    Chen, Xueman; Liu, Qiang; Song, Erwei

    2017-01-01

    A highly dynamic development process exits within the epithelia of mammary gland, featuring morphogenetic variation during puberty, pregnancy, lactation, and regression. The identification of mammary stem cells (MaSCs) via lineage-tracing studies has substantiated a hierarchical organization of the mammary epithelia. A single MaSC is capable of reconstituting the entirely functional mammary gland upon orthotopic transplantation. Although different mammary cell subpopulations can be candidate cells-of-origin for distinct breast tumor subtypes, it still lacks experimental proofs whether MaSCs, the most primitive cells, are the 'seeds' of malignant transformation during most, if not all, tumorigenesis in the breast. Here, we review current knowledge of mammary epithelial hierarchy, highlighting the roles of mammary stem/progenitor cells and breast cancer stem cells (BCSCs) along with their key molecular regulators in organ development and cancer evolution. Clarifying these issues will pave the way for developing novel interventions toward stem/progenitor cells in either prevention or treatment of breast cancer (BrCa).

  4. Mammary stem cells: angels or demons in mammary gland?

    PubMed Central

    Chen, Xueman; Liu, Qiang; Song, Erwei

    2017-01-01

    A highly dynamic development process exits within the epithelia of mammary gland, featuring morphogenetic variation during puberty, pregnancy, lactation, and regression. The identification of mammary stem cells (MaSCs) via lineage-tracing studies has substantiated a hierarchical organization of the mammary epithelia. A single MaSC is capable of reconstituting the entirely functional mammary gland upon orthotopic transplantation. Although different mammary cell subpopulations can be candidate cells-of-origin for distinct breast tumor subtypes, it still lacks experimental proofs whether MaSCs, the most primitive cells, are the ‘seeds’ of malignant transformation during most, if not all, tumorigenesis in the breast. Here, we review current knowledge of mammary epithelial hierarchy, highlighting the roles of mammary stem/progenitor cells and breast cancer stem cells (BCSCs) along with their key molecular regulators in organ development and cancer evolution. Clarifying these issues will pave the way for developing novel interventions toward stem/progenitor cells in either prevention or treatment of breast cancer (BrCa). PMID:29263909

  5. Mammary Adipose Tissue-derived Lysophospholipids Promote Estrogen Receptor-negative Mammary Epithelial Cell Proliferation

    PubMed Central

    Volden, Paul A.; Skor, Maxwell N.; Johnson, Marianna B.; Singh, Puneet; Patel, Feenalie N.; McClintock, Martha K.; Brady, Matthew J.; Conzen, Suzanne D.

    2016-01-01

    Lysophosphatidic acid (LPA), acting in an autocrine or paracrine fashion through G protein-coupled receptors, has been implicated in many physiological and pathological processes including cancer. LPA is converted to lysophosphatidylcholine (LPC) by the secreted phospholipase, autotaxin (ATX). Although various cell types can produce ATX, adipocyte-derived ATX is believed to be the major source of circulating ATX and also to be the major regulator of plasma LPA. In addition to ATX, adipocytes secrete numerous other factors (adipokines); although several adipokines have been implicated in breast cancer biology, the contribution of mammary adipose tissue-derived LPC/ATX/LPA (LPA-axis) signaling to breast cancer is poorly understood. Using mammary fat-conditioned medium, we investigated the contribution of LPA signaling to mammary epithelial cancer cell biology and identified LPA signaling as a significant contributor to the oncogenic effects of the mammary adipose tissue secretome. To interrogate the role of mammary fat in the LPA-axis during breast cancer progression, we exposed mammary adipose tissue to secreted factors from estrogen receptor-negative mammary epithelial cell lines and monitored changes in the mammary fat pad LPA-axis. Our data indicate that bidirectional interactions between mammary cancer cells and mammary adipocytes alter the local LPA-axis and increase ATX expression in the mammary fat pad during breast cancer progression. Thus, the LPC/ATX/LPA axis may be a useful target for prevention in patients at risk of ER-negative breast cancer. PMID:26862086

  6. TRIENNIAL LACTATION SYMPOSIUM/BOLFA: Plasticity of mammary development in the prepubertal bovine mammary gland.

    PubMed

    Akers, R M

    2017-12-01

    Although peripubertal mammary development represents only a small fraction of the total mass of mammary parenchyma present in the udder at the end of gestation and into lactation, there is increasing evidence that the tissue foundations created in early life can affect future mammary development and function. Studies on expression of estrogen and progesterone receptors seem to confirm the relevance of these steroids in prepubertal mammary development, but connections with other growth factors, hormones, and local tissue factors remain elusive. Enhanced preweaning feeding in the bovine appears to enhance the capacity of mammary tissue to response to mammogenic stimulation. This suggests the possibility that improved early nutrition might allow for creation of stem or progenitor cell populations to better support the massive ductal growth and lobulo-alveolar development during gestation. Increasing evidence that immune cells are involved in mammary development suggests there are unexpected and poorly understood connections between the immune system and mammary development. This is nearly unexplored in ruminants. Development of new tools to identify, isolate, and characterize cell populations within the developing bovine mammary gland offer the possibility of identifying and perhaps altering populations of mammary stem cells or selected progenitor cells to modulate mammary development and, possibly, mammary function.

  7. Pleiotrophin (PTN) Expression and Function and in the Mouse Mammary Gland and Mammary Epithelial Cells

    PubMed Central

    Rosenfield, Sonia M.; Bowden, Emma T.; Cohen-Missner, Shani; Gibby, Krissa A.; Ory, Virginie; Henke, Ralf T.; Riegel, Anna T.; Wellstein, Anton

    2012-01-01

    Expression of the heparin-binding growth factor, pleiotrophin (PTN) in the mammary gland has been reported but its function during mammary gland development is not known. We examined the expression of PTN and its receptor ALK (Anaplastic Lymphoma Kinase) at various stages of mouse mammary gland development and found that their expression in epithelial cells is regulated in parallel during pregnancy. A 30-fold downregulation of PTN mRNA expression was observed during mid-pregnancy when the mammary gland undergoes lobular-alveolar differentiation. After weaning of pups, PTN expression was restored although baseline expression of PTN was reduced significantly in mammary glands of mice that had undergone multiple pregnancies. We found PTN expressed in epithelial cells of the mammary gland and thus used a monoclonal anti-PTN blocking antibody to elucidate its function in cultured mammary epithelial cells (MECs) as well as during gland development. Real-time impedance monitoring of MECs growth, migration and invasion during anti-PTN blocking antibody treatment showed that MECs motility and invasion but not proliferation depend on the activity of endogenous PTN. Increased number of mammospheres with laminin deposition after anti-PTN blocking antibody treatment of MECs in 3D culture and expression of progenitor markers suggest that the endogenously expressed PTN inhibits the expansion and differentiation of epithelial progenitor cells by disrupting cell-matrix adhesion. In vivo, PTN activity was found to inhibit ductal outgrowth and branching via the inhibition of phospho ERK1/2 signaling in the mammary epithelial cells. We conclude that PTN delays the maturation of the mammary gland by maintaining mammary epithelial cells in a progenitor phenotype and by inhibiting their differentiation during mammary gland development. PMID:23077670

  8. Preserved hyperaemic response in (distal) string sign left internal mammary artery grafts.

    PubMed

    Hartman, Joost; Kelder, Hans; Ackerstaff, Rob; van Swieten, Henry; Vermeulen, Freddy; Bogers, Ad

    2007-02-01

    To correlate supraclavicular ultrasonography at rest and in hyperaemic response with angiographically patent and (distal) 'string sign' left internal mammary artery (LIMA) to left anterior descending (LAD) area grafts. Fifty-three patients with LIMA to LAD area grafting were prospectively entered in a follow-up study. Arteriography (native and LIMA) was performed at 1.4+/-0.8 years postoperatively and ultrasonography was performed at rest, in hyperaemic response and 2min after hyperaemic response at 1.8+/-0.8 years postoperatively and was compared to arteriography. Ultrasonographic parameters analysed were systolic and diastolic peak velocity, systolic and diastolic velocity integral, diastolic/systolic peak velocity ratio and diastolic/total velocity integral ratio. One patient was excluded because obesity hampered ultrasonography. Arteriography demonstrated functional grafts in 43 patients (group I), sequential distal 'string sign grafts' in 4 patients (group II) and total 'string sign grafts' in 5 patients (group III). Between the groups all ultrasonographic velocities showed a significant linear relation (p

  9. Malignant neoplasm in the axilla of a male: suspected primary carcinoma of an accessory mammary gland.

    PubMed

    Takeyama, Hiroshi; Takahashi, Hiroyuki; Tabei, Isao; Fukuchi, Osamu; Nogi, Hiroko; Kinoshita, Satoki; Uchida, Ken; Morikawa, Toshiaki

    2010-04-01

    A 58-year-old Japanese male patient visited our hospital for evaluation of an elastic hard mass, measuring 80 x 50 mm, in the right axillary area. Incisional biopsy for suspected malignancy was performed, and histopathologic examination by hematoxylin-eosin (H&E) staining yielded a diagnosis of poorly differentiated adenocarcinoma metastatic from an unknown primary. As the tumor was immunohistochemically positive for both ER and PgR, metastatic breast cancer was strongly suspected. Ultrasonography, CT, and MRI revealed no evidence of tumors in the bilateral mammary glands. Detailed examination of the head and neck region, lung, and upper and lower gastrointestinal tract also revealed no evidence of a primary tumor. After chemotherapy, the patient underwent tumor resection with axillary lymph node dissection. On the basis of the histological features of H&E-stained specimens and immunohistochemistry of the resected tumor, this case was diagnosed as breast cancer of unknown origin in a male. The tumor could have been an axillary lymph node metastasis from an occult breast carcinoma, or primary cancer arising in an accessory mammary gland.

  10. [Intraoperative ultrasonography during laparoscopic surgery].

    PubMed

    Alecu, L; Lungu, C; Pascu, A; Costan, I; Corodeanu, G; Deacu, A; Marin, A

    2000-01-01

    Of this study is the introduction and the results evaluation of laparoscopic ultrasonography performed. We realize a prospective study about laparoscopic ultrasonography performed in 37 cases with laparoscopic surgical treatment. The Aloka SSD 2000 mobile scanner is used. This system make possible the use of an linear-array transducer, with mechanical flexibility and availability of Doppler analysis. Most frequently we used intraoperative ultrasonography in laparoscopic cholecystectomy as an alternative for cholangiography to exclude CBD pathology. Because of various surgical pathology with laparoscopic approach, the laparoscopic ultrasonography utilization range was vastly. In all the cases we could performed the laparoscopic ultrasonography. In 6 of 27 cases with laparoscopic cholecystectomy we found pathological disorders of bile ducts. CBD with diameter found between 5-12 mm. We properly saw the distal segment of CBD in 23 cases (89.2%), and common hepatic duct in 26 cases (97.3%). The quality of visualization was very good in 21 cases (83.8%) and moderate in 6 cases (16.2%). We easy identify CBD stones and we successfully used Doppler color mode in differentiating vascular from non-vascular from non-vascular structures. Laparoscopic ultrasonography performed in a case with left colon cancer excluded liver metastasis and lymph nodes metastasis. 1. Laparoscopic ultrasonography combines the advantages of diagnostic laparoscopy and intraoperative contact ultrasonography; 2. Laparoscopic ultrasonography is a simple and very efficient intraoperative examination procedure; 3. Laparoscopic ultrasonography is the technique to choose in CBD intraoperative exploration; 4. Laparoscopic ultrasonography improve abdominal malignancy exploration, thus modifying therapeutic decisions; 5. Color Doppler mode guides the surgeon's steps in difficult directions.

  11. Mouse Mammary Tumor Virus c-rel Transgenic Mice Develop Mammary Tumors

    PubMed Central

    Romieu-Mourez, Raphaëlle; Kim, Dong W.; Min Shin, Sang; Demicco, Elizabeth G.; Landesman-Bollag, Esther; Seldin, David C.; Cardiff, Robert D.; Sonenshein, Gail E.

    2003-01-01

    Amplification, overexpression, or rearrangement of the c-rel gene, encoding the c-Rel NF-κB subunit, has been reported in solid and hematopoietic malignancies. For example, many primary human breast cancer tissue samples express high levels of nuclear c-Rel. While the Rev-T oncogene v-rel causes tumors in birds, the ability of c-Rel to transform in vivo has not been demonstrated. To directly test the role of c-Rel in breast tumorigenesis, mice were generated in which overexpression of mouse c-rel cDNA was driven by the hormone-responsive mouse mammary tumor virus long terminal repeat (MMTV-LTR) promoter, and four founder lines identified. In the first cycle of pregnancy, the expression of transgenic c-rel mRNA was observed, and levels of c-Rel protein were increased in the mammary gland. Importantly, 31.6% of mice developed one or more mammary tumors at an average age of 19.9 months. Mammary tumors were of diverse histology and expressed increased levels of nuclear NF-κB. Analysis of the composition of NF-κB complexes in the tumors revealed aberrant nuclear expression of multiple subunits, including c-Rel, p50, p52, RelA, RelB, and the Bcl-3 protein, as observed previously in human primary breast cancers. Expression of the cancer-related NF-κB target genes cyclin D1, c-myc, and bcl-xl was significantly increased in grossly normal transgenic mammary glands starting the first cycle of pregnancy and increased further in mammary carcinomas compared to mammary glands from wild-type mice or virgin transgenic mice. In transient transfection analysis in untransformed breast epithelial cells, c-Rel-p52 or -p50 heterodimers either potently or modestly induced cyclin D1 promoter activity, respectively. Lastly, stable overexpression of c-Rel resulted in increased cyclin D1 and NF-κB p52 and p50 subunit protein levels. These results indicate for the first time that dysregulated expression of c-Rel, as observed in breast cancers, is capable of contributing to mammary

  12. Mammary Gland Development

    PubMed Central

    Macias, Hector

    2012-01-01

    The mammary gland develops through several distinct stages. The first transpires in the embryo as the ectoderm forms a mammary line that resolves into placodes. Regulated by epithelial/mesenchymal interactions, the placodes descend into the underlying mesenchyme and produce the rudimentary ductal structure of the gland present at birth. Subsequent stages of development – pubertal growth, pregnancy, lactation and involution – occur postnatally under the regulation of hormones. Puberty initiates branching morphogenesis, which requires growth hormone and estrogen, as well as IGF1, to create a ductal tree that fills the fat pad. Upon pregnancy the combined actions of progesterone and prolactin generate alveoli, which secrete milk during lactation. Lack of demand for milk at weaning initiates the process of involution whereby the gland is remodeled back to its pre-pregnancy state. These processes require numerous signaling pathways that have distinct regulatory functions at different stages of gland development. Signaling pathways also regulate a specialized subpopulation of mammary stem cells that fuel the dramatic changes in the gland occurring with each pregnancy. Our knowledge of mammary gland development and mammary stem cell biology has significantly contributed to our understanding of breast cancer and has advanced the discovery of therapies to treat this disease. PMID:22844349

  13. VHL deletion impairs mammary alveologenesis but is not sufficient for mammary tumorigenesis.

    PubMed

    Seagroves, Tiffany N; Peacock, Danielle L; Liao, Debbie; Schwab, Luciana P; Krueger, Robin; Handorf, Charles R; Haase, Volker H; Johnson, Randall S

    2010-05-01

    Overexpression of hypoxia inducible factor-1 (HIF-1)alpha, which is common in most solid tumors, correlates with poor prognosis and high metastatic risk in breast cancer patients. Because HIF-1alpha protein stability is tightly controlled by the tumor suppressor von Hippel-Lindau (VHL), deletion of VHL results in constitutive HIF-1alpha expression. To determine whether VHL plays a role in normal mammary gland development, and if HIF-1alpha overexpression is sufficient to initiate breast cancer, Vhl was conditionally deleted in the mammary epithelium using the Cre/loxP system. During first pregnancy, loss of Vhl resulted in decreased mammary epithelial cell proliferation and impaired alveolar differentiation; despite these phenotypes, lactation was sufficient to support pup growth. In contrast, in multiparous dams, Vhl(-/-) mammary glands exhibited a progressive loss of alveolar epithelium, culminating in lactation failure. Deletion of Vhl in the epithelium also impacted the mammary stroma, as there was increased microvessel density accompanied by hemorrhage and increased immune cell infiltration. However, deletion of Vhl was not sufficient to induce mammary tumorigenesis in dams bred continuously for up to 24 months of age. Moreover, co-deletion of Hif1a could not rescue the Vhl(-/-)-dependent phenotype as dams were unable to successfully lactate during the first lactation. These results suggest that additional VHL-regulated genes besides HIF1A function to maintain the proliferative and regenerative potential of the breast epithelium.

  14. Characterization of Human Mammary Epithelial Stem Cells

    DTIC Science & Technology

    2010-10-01

    This term reflects the method used to detect murine mammary stem cells which is based on their individual ability to regenerate an entire mammary tree......mammary stem cells. We now describe a method for detecting an analogous subpopulation in normal human mammary tissue. Dissociated cells are suspended

  15. Lactation stage-dependent expression of transporters in rat whole mammary gland and primary mammary epithelial organoids.

    PubMed

    Gilchrist, Samuel E; Alcorn, Jane

    2010-04-01

    Since solute carrier (SLC) and ATP-binding cassette (ABC) transporters play pivotal roles in the transport of both nutrients and drugs into breast milk, drug-nutrient transport interactions at the lactating mammary gland are possible. Our purpose was to characterize lactation stage-dependent changes in transporter expression in rat mammary gland and isolated mammary epithelial organoids (MEO) to provide additional insight for the safe use of maternal medications during breastfeeding. We used quantitative reverse transcription-polymerase chain reaction to assess the temporal expression patterns of SLC and ABC transporters in rat mammary gland and isolated MEO at different stages of lactation. In whole mammary gland five distinct patterns of expression emerged relative to late gestation: (i) decreasing throughout lactation (Mdr1a, Mdr1b, Mrp1, Octn2, Ent2, Ent3, Ncbt2, Mtx1); (ii) prominent increase in early lactation, which may remain elevated or decline with advancing lactation (Octn1, Cnt2, Cnt3, Ent1, Pept1, Pept2); (iii) constant but decreasing later in lactation (Octn3, Dmt1); (iv) increasing until mid-to-late lactation (Oct1, Cnt1); and (v) prominent increase late in lactation (Ncbt1). In isolated MEO (an enriched source of mammary epithelial cells) major differences in expression patterns were noted for Octn3, Ncbt1, and Mtx1, but otherwise were reasonably similar with the whole mammary gland. In conclusion our study augments existing data on transporter expression in the lactating mammary gland. These data should facilitate investigations into lactation-stage dependent changes in drug or nutrient milk-to-serum concentration ratios, the potential for drug- or disease-transporter interactions, and mechanistic studies of transporter function in the lactating mammary gland.

  16. Establishment of mammary gland model in vitro: culture and evaluation of a yak mammary epithelial cell line.

    PubMed

    Fu, Mei; Chen, Yabing; Xiong, Xianrong; Lan, Daoliang; Li, Jian

    2014-01-01

    This study aimed to establish yak mammary epithelial cells (YMECs) for an in vitro model of yak mammary gland biology. The primary culture of YMECs was obtained from mammary gland tissues of lactating yak and then characterized using immunocytochemistry, RT-PCR, and western blot analysis. Whether foreign genes could be transfected into the YMECs were examined by transfecting the EGFP gene into the cells. Finally, the effect of Staphylococcus aureus infection on YMECs was determined. The established YMECs retained the mammary epithelial cell characteristics. A spontaneously immortalized yak mammary epithelial cell line was established and could be continuously subcultured for more than 60 passages without senescence. The EGFP gene was successfully transferred into the YMECs, and the transfected cells could be maintained for a long duration in the culture by continuous subculturing. The cells expressed more antimicrobial peptides upon S.aureus invasion. Therefore, the established cell line could be considered a model system to understand yak mammary gland biology.

  17. Pim-1 kinase expression during murine mammary development

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gapter, Leslie A.; School of Molecular Biosciences, Washington State University, Pullman, WA 99164-4234; Magnuson, Nancy S.

    2006-07-07

    Pim-1 kinase phosphorylates substrates whose activities are linked to proliferation, survival, differentiation, and apoptosis. Although pim-1 is induced by hormones and cytokines, the hormonal control and contribution of Pim-1 to mammary gland development have not been evaluated. We examined Pim-1 expression in mammary cell lines, investigated whether Pim-1 levels could be altered in breast epithelia by mammogenic hormones, and evaluated Pim-1 expression during mammary development. We found that Pim-1 was elevated in most mammary carcinoma cell lines and progesterone increased Pim-1 protein to some extent in non-tumorigenic mammary epithelia. Pim-1 expression in situ was consistent with the documented profile ofmore » progesterone activity in mouse mammary glands. Pim-1 nuclear localization correlated with cytoplasmic distribution for its substrate, p21{sup CIP/Waf1}, and we found that Pim-1 and p21 associate in vitro. Our results suggest that Pim-1 expression may be regulated by progesterone during mammary development and Pim-1 associates with p21 in mammary epithelial cells.« less

  18. Preserved hyperaemic response in supraclavicular ultrasonography demonstrates function on demand of the LIMA to LAD string sign graft after CABG.

    PubMed

    Hartman, J M; Kelder, H C; Ackerstaff, R G A; Swieten, H A; Vermeulen, F E E; Bogers, A J J C

    2007-02-01

    To correlate supraclavicular ultrasonography with angiographically patent and string sign left internal mammary artery (LIMA) to left anterior descending artery (LAD) grafts. Sixteen patients with a single LIMA anastomosis to the LAD were prospectively entered in a follow-up study. The supraclavicular ultrasonography of the LIMA origin was studied preoperatively and at 5.3+/-3.6 months and 1.7+/-0.4 year postoperatively. At the late postoperative ultrasonography electrocardiographically controlled hyperemic response was also studied for 6 min. Control angiography was performed at 1.5+/-0.8 year. Differences within groups were tested with a paired t-test and between groups with an unpaired t-test. Control angiography showed in 13 patients (group I) a patent LIMA graft and in 3 patients (group II) a string sign LIMA graft. Preoperative blood velocities were not significantly different between groups. Postoperatively, both groups revealed higher diastolic and lower systolic blood velocities compared to preoperative values. The blood velocities at rest did not change in group I and all velocities decreased in group II in time postoperatively. The blood velocities in maximal hyperemic response increased significantly within the groups and were not significantly different between the groups. No ischemia could be detected electrocardiographically during hyperemic response and no patient presented angina. Both groups showed a shift towards coronary type diastolic blood velocities at rest and at hyperaemic response. Significant hyperemic response was also present in string sign LIMA grafts and demonstrates response capacity to increased myocardial oxygen demand.

  19. Mammary and extramammary Paget's disease

    PubMed Central

    Lloyd, J; Flanagan, A

    2000-01-01

    Mammary and extramammary Paget's disease are uncommon intraepithelial adenocarcinomas. Both conditions have similar clinical features, which mimic inflammatory and infective diseases. Histological diagnostic confusion can arise between Paget's disease and other neoplastic conditions affecting the skin, with the most common differential diagnoses being malignant melanoma and atypical squamous disease. The glandular differentiation of both mammary Paget's disease and extramammary Paget's disease is indicated by morphological appearances, the presence of intracellular mucin in many cases, and positive immunohistochemical staining for glandular cytokeratins, epithelial membrane antigen, and carcinoembryonic antigen. This article provides an overview of mammary and extramammary Paget's disease and discusses recent evidence regarding the cell of origin. The concepts of primary and secondary Paget's disease are presented and the differential diagnosis is discussed with reference to immunohistochemical markers that might be of diagnostic value. Key Words: mammary Paget's disease • extramammary Paget's disease PMID:11064666

  20. B-mode ultrasound examination of canine mammary gland neoplastic lesions of small size (diameter < 2 cm).

    PubMed

    Vannozzi, Iacopo; Tesi, Matteo; Zangheri, Marta; Innocenti, Viola Maria; Rota, Alessandra; Citi, Simonetta; Poli, Alessandro

    2018-06-01

    Ultrasonography is a valuable tool for the evaluation of neoplastic lesions in the dog and there is a growing interest in the use of this technique for the stadiation of canine mammary tumours. An accurate assessment of small sized nodules facilitates the stadiation of the mammary lesions and helps the clinician in the choice of the most indicated surgical therapy. The aim of this study was to identify those ultrasound criteria that may be useful in discriminating between benign and malignant lesions of small size (diameter smaller than 2 cm). Sixty-two nodules, < 2 cm in larger diameter, belonging to thirty-five bitches presented between January 2012 and February 2014 were evaluated. Tumours were observed by conventional ultrasound and assessed for: shape (regular-irregular), limit (defined-ill-defined), margins (regular-irregular), echogenicity (hypoechoic-isoechoic-hyperecoic), echotexture (homogeneus-heterogeneus), presence of hyperecoic halo, distal acoustic enhancement or shadowing and surrounding tissue alterations. Among the alterations in surrounding tissues, the disruption of the glandular tissue and the increase in echogenicity of the peritumoral tissues were assessed. Thereafter, bitches were subjected to mastectomy and nodules were evaluated histologically. None of the ultasound criteria considered in the current study showed a statistically significant relation with malignancy, except for the presence of alterations in the tissue surrounding the nodules. According to our results, this characteristic may indicate malignancy, however its subjectivity may affect the applicability in clinical practice. In conclusions, conventional ultrasound in bitches had a limited ability in discriminating benign and malignant mammary gland neoplastic lesions of small size (diameter < 2 cm).

  1. A mammary cell-specific enhancer in mouse mammary tumor virus DNA is composed of multiple regulatory elements including binding sites for CTF/NFI and a novel transcription factor, mammary cell-activating factor.

    PubMed Central

    Mink, S; Härtig, E; Jennewein, P; Doppler, W; Cato, A C

    1992-01-01

    Mouse mammary tumor virus (MMTV) is a milk-transmitted retrovirus involved in the neoplastic transformation of mouse mammary gland cells. The expression of this virus is regulated by mammary cell type-specific factors, steroid hormones, and polypeptide growth factors. Sequences for mammary cell-specific expression are located in an enhancer element in the extreme 5' end of the long terminal repeat region of this virus. This enhancer, when cloned in front of the herpes simplex thymidine kinase promoter, endows the promoter with mammary cell-specific response. Using functional and DNA-protein-binding studies with constructs mutated in the MMTV long terminal repeat enhancer, we have identified two main regulatory elements necessary for the mammary cell-specific response. These elements consist of binding sites for a transcription factor in the family of CTF/NFI proteins and the transcription factor mammary cell-activating factor (MAF) that recognizes the sequence G Pu Pu G C/G A A G G/T. Combinations of CTF/NFI- and MAF-binding sites or multiple copies of either one of these binding sites but not solitary binding sites mediate mammary cell-specific expression. The functional activities of these two regulatory elements are enhanced by another factor that binds to the core sequence ACAAAG. Interdigitated binding sites for CTF/NFI, MAF, and/or the ACAAAG factor are also found in the 5' upstream regions of genes encoding whey milk proteins from different species. These findings suggest that mammary cell-specific regulation is achieved by a concerted action of factors binding to multiple regulatory sites. Images PMID:1328867

  2. Postoperative ultrasonography of the musculoskeletal system.

    PubMed

    Chun, Kyung Ah; Cho, Kil-Ho

    2015-07-01

    Ultrasonography of the postoperative musculoskeletal system plays an important role in the accurate diagnosis of abnormal lesions in the bone and soft tissues. Ultrasonography is a fast and reliable method with no harmful irradiation for the evaluation of postoperative musculoskeletal complications. In particular, it is not affected by the excessive metal artifacts that appear on computed tomography or magnetic resonance imaging. Another benefit of ultrasonography is its capability to dynamically assess the pathologic movement in joints, muscles, or tendons. This article discusses the frequent applications of musculoskeletal ultrasonography in various postoperative situations including those involving the soft tissues around the metal hardware, arthroplasty, postoperative tendons, recurrent soft tissue tumors, bone unions, and amputation surgery.

  3. Mammary gland involution is associated with rapid down regulation of major mammary Ca**2+-ATPases

    USDA-ARS?s Scientific Manuscript database

    Sixty percent of calcium in milk is transported across the mammary cells apical membrane by the plasma membrane Ca**2+-ATPase 2 (PMCA2). The effect of abrupt cessation of milk production on the Ca**2+-ATPases and mammary calcium transport is unknown. We found that 24 hours after stopping milk prod...

  4. Ultrasonography versus computed tomography for suspected nephrolithiasis.

    PubMed

    Smith-Bindman, Rebecca; Aubin, Chandra; Bailitz, John; Bengiamin, Rimon N; Camargo, Carlos A; Corbo, Jill; Dean, Anthony J; Goldstein, Ruth B; Griffey, Richard T; Jay, Gregory D; Kang, Tarina L; Kriesel, Dana R; Ma, O John; Mallin, Michael; Manson, William; Melnikow, Joy; Miglioretti, Diana L; Miller, Sara K; Mills, Lisa D; Miner, James R; Moghadassi, Michelle; Noble, Vicki E; Press, Gregory M; Stoller, Marshall L; Valencia, Victoria E; Wang, Jessica; Wang, Ralph C; Cummings, Steven R

    2014-09-18

    There is a lack of consensus about whether the initial imaging method for patients with suspected nephrolithiasis should be computed tomography (CT) or ultrasonography. In this multicenter, pragmatic, comparative effectiveness trial, we randomly assigned patients 18 to 76 years of age who presented to the emergency department with suspected nephrolithiasis to undergo initial diagnostic ultrasonography performed by an emergency physician (point-of-care ultrasonography), ultrasonography performed by a radiologist (radiology ultrasonography), or abdominal CT. Subsequent management, including additional imaging, was at the discretion of the physician. We compared the three groups with respect to the 30-day incidence of high-risk diagnoses with complications that could be related to missed or delayed diagnosis and the 6-month cumulative radiation exposure. Secondary outcomes were serious adverse events, related serious adverse events (deemed attributable to study participation), pain (assessed on an 11-point visual-analogue scale, with higher scores indicating more severe pain), return emergency department visits, hospitalizations, and diagnostic accuracy. A total of 2759 patients underwent randomization: 908 to point-of-care ultrasonography, 893 to radiology ultrasonography, and 958 to CT. The incidence of high-risk diagnoses with complications in the first 30 days was low (0.4%) and did not vary according to imaging method. The mean 6-month cumulative radiation exposure was significantly lower in the ultrasonography groups than in the CT group (P<0.001). Serious adverse events occurred in 12.4% of the patients assigned to point-of-care ultrasonography, 10.8% of those assigned to radiology ultrasonography, and 11.2% of those assigned to CT (P=0.50). Related adverse events were infrequent (incidence, 0.4%) and similar across groups. By 7 days, the average pain score was 2.0 in each group (P=0.84). Return emergency department visits, hospitalizations, and diagnostic

  5. Number and location of mouse mammary tumor virus proviral DNA in mouse DNA of normal tissue and of mammary tumors.

    PubMed Central

    Groner, B; Hynes, N E

    1980-01-01

    The Southern DNA filter transfer technique was used to characterize the genomic location of the mouse mammary tumor proviral DNA in different inbred strains of mice. Two of the strains (C3H and CBA) arose from a cross of a Bagg albino (BALB/c) mouse and a DBA mouse. The mouse mammary tumor virus-containing restriction enzyme DNA fragments of these strains had similar patterns, suggesting that the proviruses of these mice are in similar genomic locations. Conversely, the pattern arising from the DNA of the GR mouse, a strain genetically unrelated to the others, appeared different, suggesting that its mouse mammary tumor proviruses are located in different genomic sites. The structure of another gene, that coding for beta-globin, was also compared. The mice strains which we studied can be categorized into two classes, expressing either one or two beta-globin proteins. The macroenvironment of the beta-globin gene appeared similar among the mice strains belonging to one genetic class. Female mice of the C3H strain exogenously transmit mouse mammary tumor virus via the milk, and their offspring have a high incidence of mammary tumor occurrence. DNA isolated from individual mammary tumors taken from C3H mice or from BALB/c mice foster nursed on C3H mothers was analyzed by the DNA filter transfer technique. Additional mouse mammary tumor virus-containing fragments were found in the DNA isolated from each mammary tumor. These proviral sequences were integrated into different genomic sites in each tumor. Images PMID:6245257

  6. Lgr6 labels a rare population of mammary gland progenitor cells that are able to originate luminal mammary tumours

    PubMed Central

    Messal, Hendrik A.; Andersson, Agneta B.; Ruiz, E. Josue; Gerling, Marco; Douagi, Iyadh; Spencer-Dene, Bradley; Musch, Alexandra; Mitter, Richard; Bhaw, Leena; Stone, Richard; Bornhorst, Dorothee; Sesay, Abdul K.; Jonkers, Jos; Stamp, Gordon; Malanchi, Ilaria; Toftgård, Rune; Behrens, Axel

    2018-01-01

    The mammary gland is composed of a complex cellular hierarchy with unusual postnatal plasticity. The identities of stem/progenitor cell populations, as well as tumour-initiating cells that give rise to breast cancer, are incompletely understood. Here we show that Lgr6 marks rare populations of cells in both basal and luminal mammary gland compartments in mice. Lineage tracing analysis showed that Lgr6+ cells are unipotent progenitors, which expand clonally during puberty but diminish in adulthood. In pregnancy or upon stimulation with ovarian hormones, adult Lgr6+ cells regained proliferative potency and their progeny formed alveoli over repeated pregnancies. Oncogenic mutations in Lgr6+ cells resulted in expansion of luminal cells, culminating in mammary gland tumours. Conversely, depletion of Lgr6+ cells in the MMTV-PyMT model of mammary tumourigenesis significantly impaired tumour growth. Thus, Lgr6 marks mammary gland progenitor cells that can initiate tumours, and cells of luminal breast tumours required for efficient tumour maintenance. PMID:27798604

  7. Microenvironmental Regulation of Mammary Carcinogenesis

    DTIC Science & Technology

    2008-06-01

    cells. These models share many of the hallmarks of multistage human breast cancer development including histological disease progression and immune cell... developed by Muller and colleagues20, represents a reasonable recapitulation of late-stage human breast cancer as determined by histological progression ...Annual Progress Report d. Develop a profile of proteolytic activities in normal and neoplastic mammary tissues from mouse models of mammary

  8. Mammary Cancer and Activation of Transposable Elements

    DTIC Science & Technology

    2015-03-01

    EGFP). No other cell type in the mammary fat pad was observed to express EGFP. Wholemount and FACS analyses of mammary fat pads after involution from...were sacrificed for PI-MEC isolation in groups of up to 4 control or cancer-prone uniparous or triparous females. Both 4 th mammary fat pads were...to unknown reason (n=46), and smaller numbers of animals with various conditions (malocclusion, head tilt , dystocia, respiratory complaints, identity

  9. SOCS3 promotes apoptosis of mammary differentiated cells.

    PubMed

    Le Provost, Fabienne; Miyoshi, Keiko; Vilotte, Jean-Luc; Bierie, Brian; Robinson, Gertraud W; Hennighausen, Lothar

    2005-12-30

    Growth and function of the mammary gland is regulated by cytokines and modulated by suppressor of cytokine signalling (SOCS) proteins. In vitro experiments demonstrated that SOCS3 can inhibit PRL induction of milk protein gene expression and STAT5 activation. We explored the SOCS3 expression pattern during mouse mammary development and its regulation by PRL and GH in wild-type and STAT5a-null mammary tissue. Our results suggest that, in vivo, PRL stimulates SOCS3 expression in stromal adipocytes, independently of STAT5a stimulation. In mammary epithelial cells, SOCS3 expression appears to be related to STAT3 activation. Together, our results are consistent with a role of SOCS3 in the mammary gland by promoting apoptosis of differentiated cells (adipocytes during gestation and epithelial cells during involution).

  10. CLINICOPATHOLOGIC FEATURES OF MAMMARY MASSES IN CAPTIVE LIONS (PANTHERA LEO).

    PubMed

    Sadler, Ryan A; Craig, Linden E; Ramsay, Edward C; Helmick, Kelly; Collins, Darin; Garner, Michael M

    2016-03-01

    A multi-institutional retrospective analysis of 330 pathology accessions from 285 different lions found 15 captive, female African lions (Panthera leo) with confirmed mammary masses. Aside from the presence of a mammary mass, the most common initial clinical sign was inappetence. Histologic diagnoses were predominantly adenocarcinoma (n = 12), though two benign masses (mammary hyperplasia and a mammary cyst) and one squamous cell carcinoma were identified. Nine of 13 malignant tumors had metastasized to lymph nodes or viscera at the time of necropsy. Six lions with adenocarcinoma and two lions with benign mammary masses had received hormonal contraception, though little evidence of mammary lobular hyperplasia was seen in association with the adenocarcinomas. The most common concurrent disease processes found at necropsy were chronic urinary tract disease and other malignancies. These cases demonstrate that mammary malignancies occur in captive lions and frequently metastasize.

  11. Value of ultrasonography for detecting chronic injury of the lateral ligaments of the ankle joint compared with ultrasonography findings.

    PubMed

    Cheng, Y; Cai, Y; Wang, Y

    2014-01-01

    The aim of this study was to assess the accuracy of ultrasonography in the diagnosis of chronic lateral ankle ligament injury. A total of 120 ankles in 120 patients with a clinical suspicion of chronic ankle ligament injury were examined by ultrasonography by using a 5- to 17-MHz linear array transducer before surgery. The results of ultrasonography were compared with the operative findings. There were 18 sprains and 24 partial and 52 complete tears of the anterior talofibular ligament (ATFL); 26 sprains, 27 partial and 12 complete tears of the calcaneofibular ligament (CFL); and 1 complete tear of the posterior talofibular ligament (PTFL) at arthroscopy and operation. Compared with operative findings, the sensitivity, specificity and accuracy of ultrasonography were 98.9%, 96.2% and 84.2%, respectively, for injury of the ATFL and 93.8%, 90.9% and 83.3%, respectively, for injury of the CFL. The PTFL tear was identified by ultrasonography. The accuracy of identification between acute-on-chronic and subacute-chronic patients did not differ. The accuracies of diagnosing three grades of ATFL injuries were almost the same as those of diagnosing CFL injuries. Ultrasonography provides useful information for the evaluation of patients presenting with chronic pain after ankle sprain. Intraoperative findings are the reference standard. We demonstrated that ultrasonography was highly sensitive and specific in detecting chronic lateral ligments injury of the ankle joint.

  12. Pueraria mirifica Exerts Estrogenic Effects in the Mammary Gland and Uterus and Promotes Mammary Carcinogenesis in Donryu Rats

    PubMed Central

    Kakehashi, Anna; Yoshida, Midori; Tago, Yoshiyuki; Ishii, Naomi; Okuno, Takahiro; Gi, Min; Wanibuchi, Hideki

    2016-01-01

    Pueraria mirifica (PM), a plant whose dried and powdered tuberous roots are now widely used in rejuvenating preparations to promote youthfulness in both men and women, may have major estrogenic influence. In this study, we investigated modifying effects of PM at various doses on mammary and endometrial carcinogenesis in female Donryu rats. Firstly, PM administered to ovariectomized animals at doses of 0.03%, 0.3%, and 3% in a phytoestrogen-low diet for 2 weeks caused significant increase in uterus weight. Secondly, a 4 week PM application to non-operated rats at a dose of 3% after 7,12-dimethylbenz[a]anthracene (DMBA) initiation resulted in significant elevation of cell proliferation in the mammary glands. In a third experiment, postpubertal administration of 0.3% (200 mg/kg body weight (b.w.)/day) PM to 5-week-old non-operated animals for 36 weeks following initiation of mammary and endometrial carcinogenesis with DMBA and N-ethyl-N′-nitro-N-nitrosoguanidine (ENNG), respectively, resulted in significant increase of mammary adenocarcinoma incidence. A significant increase of endometrial atypical hyperplasia multiplicity was also observed. Furthermore, PM at doses of 0.3%, and more pronouncedly, at 1% induced dilatation, hemorrhage and inflammation of the uterine wall. In conclusion, postpubertal long-term PM administration to Donryu rats exerts estrogenic effects in the mammary gland and uterus, and at a dose of 200 mg/kg b.w./day was found to promote mammary carcinogenesis initiated by DMBA. PMID:27827907

  13. Pueraria mirifica Exerts Estrogenic Effects in the Mammary Gland and Uterus and Promotes Mammary Carcinogenesis in Donryu Rats.

    PubMed

    Kakehashi, Anna; Yoshida, Midori; Tago, Yoshiyuki; Ishii, Naomi; Okuno, Takahiro; Gi, Min; Wanibuchi, Hideki

    2016-11-04

    Pueraria mirifica (PM), a plant whose dried and powdered tuberous roots are now widely used in rejuvenating preparations to promote youthfulness in both men and women, may have major estrogenic influence. In this study, we investigated modifying effects of PM at various doses on mammary and endometrial carcinogenesis in female Donryu rats. Firstly, PM administered to ovariectomized animals at doses of 0.03%, 0.3%, and 3% in a phytoestrogen-low diet for 2 weeks caused significant increase in uterus weight. Secondly, a 4 week PM application to non-operated rats at a dose of 3% after 7,12-dimethylbenz[a]anthracene (DMBA) initiation resulted in significant elevation of cell proliferation in the mammary glands. In a third experiment, postpubertal administration of 0.3% (200 mg/kg body weight (b.w.)/day) PM to 5-week-old non-operated animals for 36 weeks following initiation of mammary and endometrial carcinogenesis with DMBA and N -ethyl- N '-nitro- N -nitrosoguanidine (ENNG), respectively, resulted in significant increase of mammary adenocarcinoma incidence. A significant increase of endometrial atypical hyperplasia multiplicity was also observed. Furthermore, PM at doses of 0.3%, and more pronouncedly, at 1% induced dilatation, hemorrhage and inflammation of the uterine wall. In conclusion, postpubertal long-term PM administration to Donryu rats exerts estrogenic effects in the mammary gland and uterus, and at a dose of 200 mg/kg b.w./day was found to promote mammary carcinogenesis initiated by DMBA.

  14. Compression ultrasonography of the lower extremity with portable vascular ultrasonography can accurately detect deep venous thrombosis in the emergency department.

    PubMed

    Crisp, Jonathan G; Lovato, Luis M; Jang, Timothy B

    2010-12-01

    Compression ultrasonography of the lower extremity is an established method of detecting proximal lower extremity deep venous thrombosis when performed by a certified operator in a vascular laboratory. Our objective is to determine the sensitivity and specificity of bedside 2-point compression ultrasonography performed in the emergency department (ED) with portable vascular ultrasonography for the detection of proximal lower extremity deep venous thrombosis. We did this by directly comparing emergency physician-performed ultrasonography to lower extremity duplex ultrasonography performed by the Department of Radiology. This was a prospective, cross-sectional study and diagnostic test assessment of a convenience sample of ED patients with a suspected lower extremity deep venous thrombosis, conducted at a single-center, urban, academic ED. All physicians had a 10-minute training session before enrolling patients. ED compression ultrasonography occurred before Department of Radiology ultrasonography and involved identification of 2 specific points: the common femoral and popliteal vessels, with subsequent compression of the common femoral and popliteal veins. The study result was considered positive for proximal lower extremity deep venous thrombosis if either vein was incompressible or a thrombus was visualized. Sensitivity and specificity were calculated with the final radiologist interpretation of the Department of Radiology ultrasonography as the criterion standard. A total of 47 physicians performed 199 2-point compression ultrasonographic examinations in the ED. Median number of examinations per physician was 2 (range 1 to 29 examinations; interquartile range 1 to 5 examinations). There were 45 proximal lower extremity deep venous thromboses observed on Department of Radiology evaluation, all correctly identified by ED 2-point compression ultrasonography. The 153 patients without proximal lower extremity deep venous thrombosis all had a negative ED compression

  15. The mammary cellular hierarchy and breast cancer.

    PubMed

    Oakes, Samantha R; Gallego-Ortega, David; Ormandy, Christopher J

    2014-11-01

    Advances in the study of hematopoietic cell maturation have paved the way to a deeper understanding the stem and progenitor cellular hierarchy in the mammary gland. The mammary epithelium, unlike the hematopoietic cellular hierarchy, sits in a complex niche where communication between epithelial cells and signals from the systemic hormonal milieu, as well as from extra-cellular matrix, influence cell fate decisions and contribute to tissue homeostasis. We review the discovery, definition and regulation of the mammary cellular hierarchy and we describe the development of the concepts that have guided our investigations. We outline recent advances in in vivo lineage tracing that is now challenging many of our assumptions regarding the behavior of mammary stem cells, and we show how understanding these cellular lineages has altered our view of breast cancer.

  16. Mammary Stem Cells: Premise, Properties, and Perspectives.

    PubMed

    Lloyd-Lewis, Bethan; Harris, Olivia B; Watson, Christine J; Davis, Felicity M

    2017-08-01

    Adult mammary stem cells (MaSCs) drive postnatal organogenesis and remodeling in the mammary gland, and their longevity and potential have important implications for breast cancer. However, despite intense investigation the identity, location, and differentiation potential of MaSCs remain subject to deliberation. The application of genetic lineage-tracing models, combined with quantitative 3D imaging and biophysical methods, has provided new insights into the mammary epithelial hierarchy that challenge classical definitions of MaSC potency and behaviors. We review here recent advances - discussing fundamental unresolved properties of MaSC potency, dynamics, and plasticity - and point to evolving technologies that promise to shed new light on this intractable debate. Elucidation of the physiological mammary differentiation hierarchy is paramount to understanding the complex heterogeneous breast cancer landscape. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Genistein-mediated inhibition of mammary stromal adipocyte differentiation limits expansion of mammary stem/progenitor cells by paracrine signaling

    USDA-ARS?s Scientific Manuscript database

    Mammary adiposity may contribute to breast cancer development and progression by releasing cytokines and other inflammatory mediators that promote mammary epithelial proliferation. We evaluated the effects of soy isoflavone genistein (GEN) on the adipogenic differentiation of a SV40-immortalized mou...

  18. Elevated circulating IGF-I promotes mammary gland development and proliferation.

    PubMed

    Cannata, Dara; Lann, Danielle; Wu, Yingjie; Elis, Sebastien; Sun, Hui; Yakar, Shoshana; Lazzarino, Deborah A; Wood, Teresa L; Leroith, Derek

    2010-12-01

    Animal studies have shown that IGF-I is essential for mammary gland development. Previous studies have suggested that local IGF-I rather than circulating IGF-I is the major mediator of mammary gland development. In the present study we used the hepatic IGF-I transgenic (HIT) and IGF-I knockout/HIT (KO-HIT) mouse models to examine the effects of enhanced circulating IGF-I on mammary development in the presence and absence of local IGF-I. HIT mice express the rat IGF-I transgene under the transthyretin promoter in the liver and have elevated circulating IGF-I and normal tissue IGF-I levels. The KO-HIT mice have no tissue IGF-I and increased circulating IGF-I. Analysis of mammary gland development reveals a greater degree of complexity in HIT mice as compared to control and KO-HIT mice, which demonstrate similar degrees of mammary gland complexity. Immunohistochemical evaluation of glands of HIT mice also suggests an enhanced degree of proliferation of the mammary gland, whereas KO-HIT mice exhibit mammary gland proliferation similar to control mice. In addition, HIT mice have a higher percentage of proliferating myoepithelial and luminal cells than control mice, whereas KO-HIT mice have an equivalent percentage of proliferating myoepithelial and luminal cells as control mice. Thus, our findings show that elevated circulating IGF-I levels are sufficient to promote normal pubertal mammary epithelial development. However, HIT mice demonstrate more pronounced mammary gland development when compared to control and KO-HIT mice. This suggests that both local and endocrine IGF-I play roles in mammary gland development and that elevated circulating IGF-I accelerates mammary epithelial proliferation.

  19. Prenatal Imaging: Ultrasonography and Magnetic Resonance Imaging

    PubMed Central

    Reddy, Uma M.; Filly, Roy A.; Copel, Joshua A.

    2009-01-01

    The Eunice Kennedy Shriver National Institute of Child Health and Human Development held a workshop on September 18–19, 2006, to summarize the available evidence on the role and performance of current fetal imaging technology and to establish a research agenda. Ultrasonography is the imaging modality of choice for pregnancy evaluation due to its relatively low cost, real-time capability, safety, and operator comfort and experience. First-trimester ultrasonography extends the available window for fetal observation and raises the possibility of performing an early anatomic survey. Three-dimensional ultrasonography has the potential to expand the clinical application of ultrasonography by permitting local acquisition of volumes and remote review and interpretation at specialized centers. New advances allow performance of fetal magnetic resonance imaging (MRI) without maternal or fetal sedation, with improved characterization and prediction of prognosis of certain fetal central nervous system anomalies such as ventriculomegaly when compared with ultrasonography. Fewer data exist on the usefulness of fetal MRI for non–central nervous system anomalies. PMID:18591320

  20. Downregulation of ATM Gene and Protein Expression in Canine Mammary Tumors.

    PubMed

    Raposo-Ferreira, T M M; Bueno, R C; Terra, E M; Avante, M L; Tinucci-Costa, M; Carvalho, M; Cassali, G D; Linde, S D; Rogatto, S R; Laufer-Amorim, R

    2016-11-01

    The ataxia telangiectasia mutated (ATM) gene encodes a protein associated with DNA damage repair and maintenance of genomic integrity. In women, ATM transcript and protein downregulation have been reported in sporadic breast carcinomas, and the absence of ATM protein expression has been associated with poor prognosis. The aim of this study was to evaluate ATM gene and protein expression in canine mammary tumors and their association with clinical outcome. ATM gene and protein expression was evaluated by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, respectively, in normal mammary gland samples (n = 10), benign mammary tumors (n = 11), nonmetastatic mammary carcinomas (n = 19), and metastatic mammary carcinomas (n = 11). Lower ATM transcript levels were detected in benign mammary tumors and carcinomas compared with normal mammary glands (P = .011). Similarly, lower ATM protein expression was observed in benign tumors (P = .0003), nonmetastatic mammary carcinomas (P < .0001), and the primary sites of metastatic carcinomas (P < .0001) compared with normal mammary glands. No significant differences in ATM gene or protein levels were detected among benign tumors and nonmetastatic and metastatic mammary carcinomas (P > .05). The levels of ATM gene or protein expression were not significantly associated with clinical and pathological features or with survival. Similar to human breast cancer, the data in this study suggest that ATM gene and protein downregulation is involved in canine mammary gland tumorigenesis. © The Author(s) 2016.

  1. Value of ultrasonography for detecting chronic injury of the lateral ligaments of the ankle joint compared with ultrasonography findings

    PubMed Central

    Cheng, Y; Cai, Y

    2014-01-01

    Objective: The aim of this study was to assess the accuracy of ultrasonography in the diagnosis of chronic lateral ankle ligament injury. Methods: A total of 120 ankles in 120 patients with a clinical suspicion of chronic ankle ligament injury were examined by ultrasonography by using a 5- to 17-MHz linear array transducer before surgery. The results of ultrasonography were compared with the operative findings. Results: There were 18 sprains and 24 partial and 52 complete tears of the anterior talofibular ligament (ATFL); 26 sprains, 27 partial and 12 complete tears of the calcaneofibular ligament (CFL); and 1 complete tear of the posterior talofibular ligament (PTFL) at arthroscopy and operation. Compared with operative findings, the sensitivity, specificity and accuracy of ultrasonography were 98.9%, 96.2% and 84.2%, respectively, for injury of the ATFL and 93.8%, 90.9% and 83.3%, respectively, for injury of the CFL. The PTFL tear was identified by ultrasonography. The accuracy of identification between acute-on-chronic and subacute–chronic patients did not differ. The accuracies of diagnosing three grades of ATFL injuries were almost the same as those of diagnosing CFL injuries. Conclusion: Ultrasonography provides useful information for the evaluation of patients presenting with chronic pain after ankle sprain. Advances in knowledge: Intraoperative findings are the reference standard. We demonstrated that ultrasonography was highly sensitive and specific in detecting chronic lateral ligments injury of the ankle joint. PMID:24352708

  2. Peroxisomal membrane channel Pxmp2 in the mammary fat pad is essential for stromal lipid homeostasis and for development of mammary gland epithelium in mice.

    PubMed

    Vapola, Miia H; Rokka, Aare; Sormunen, Raija T; Alhonen, Leena; Schmitz, Werner; Conzelmann, Ernst; Wärri, Anni; Grunau, Silke; Antonenkov, Vasily D; Hiltunen, J Kalervo

    2014-07-01

    To understand the functional role of the peroxisomal membrane channel Pxmp2, mice with a targeted disruption of the Pxmp2 gene were generated. These mice were viable, grew and bred normally. However, Pxmp2(-/-) female mice were unable to nurse their pups. Lactating mammary gland epithelium displayed secretory lipid droplets and milk proteins, but the size of the ductal system was greatly reduced. Examination of mammary gland development revealed that retarded mammary ductal outgrowth was due to reduced proliferation of epithelial cells during puberty. Transplantation experiments established the Pxmp2(-/-) mammary stroma as a tissue responsible for suppression of epithelial growth. Morphological and biochemical examination confirmed the presence of peroxisomes in the mammary fat pad adipocytes, and functional Pxmp2 was detected in the stroma of wild-type mammary glands. Deletion of Pxmp2 led to an elevation in the expression of peroxisomal proteins in the mammary fat pad but not in liver or kidney of transgenic mice. Lipidomics of Pxmp2(-/-)mammary fat pad showed a decrease in the content of myristic acid (C14), a principal substrate for protein myristoylation and a potential peroxisomal β-oxidation product. Analysis of complex lipids revealed a reduced concentration of a variety of diacylglycerols and phospholipids containing mostly polyunsaturated fatty acids that may be caused by activation of lipid peroxidation. However, an antioxidant-containing diet did not stimulate mammary epithelial proliferation in Pxmp2(-/-) mice. The results point to disturbances of lipid metabolism in the mammary fat pad that in turn may result in abnormal epithelial growth. The work reveals impaired mammary gland development as a new category of peroxisomal disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Dicer in Mammary Tumor Stem Cell Maintenance

    DTIC Science & Technology

    2006-03-01

    we are cloning small RNAs from mammary stem cells in order to determine the regulatory niches that miRNAs may fill in this cell type. Our ultimate goal is to assess the role of Dicer in mammary tumor stem cell maintenance.

  4. How useful is abdominal ultrasonography in dogs with diarrhoea?

    PubMed

    Mapletoft, E K; Allenspach, K; Lamb, C R

    2018-01-01

    To assess the utility of abdominal ultrasonography in the diagnostic work-up of dogs with diarrhoea. Retrospective cross-sectional study based on a referral population of dogs with diarrhoea. Associations between the clinical signs, use of abdominal ultrasonography, results of abdominal ultrasonography and subsequent work-up were examined. The utility of abdominal ultrasonography was scored as high, moderate, none or counterproductive based on review of medical records. Medical records of 269 dogs were reviewed, of which 149 (55%) had abdominal ultrasonography. The most frequent result was no ultrasonographic abnormalities affecting the intestine in 65 (44%) dogs. Ultrasonography results were associated with subsequent work-up as follows: (1) no detected abnormalities and dietary trial; (2) focal thickening of the intestinal wall, loss of intestinal wall layers or enlarged abdominal lymph nodes and ultrasound-guided fine-needle aspirates; (3) diffuse thickening of the intestinal wall or hyperechoic striations in the small intestinal mucosa and endoscopy; and (4) small intestinal foreign body and coeliotomy. Abdominal ultrasonography was considered to be diagnostic without further testing in only four (3%) dogs: two had a portosystemic shunt identified ultrasonographically, one had a linear foreign body and one had a perforated pyloric ulcer. Abdominal ultrasonography had moderate utility in 56 (38%) dogs and no utility in 79 (53%) dogs. Abdominal ultrasonography was considered counterproductive in 10 (7%) dogs because results were either falsely negative or falsely positive. These results should prompt clinicians to reconsider routine use of abdominal ultrasonography in dogs with diarrhoea. © 2017 British Small Animal Veterinary Association.

  5. Mammary Hypertrophy in an Ovariohysterectomized Cat

    PubMed Central

    Pukay, B.P.; Stevenson, D.A.

    1983-01-01

    A four year old ovariohysterectomized domestic short-haired cat under treatment for behavioral urine spraying and idiopathic alopecia developed mammary gland hypertrophy following treatment with megestrol acetate. Withdrawal of the progestin and treatment with androgen failed to cause regression of the hypertrophy. The affected mammary gland was surgically excised and recovery was uneventful. ImagesFigure 1. PMID:17422254

  6. The spectrum of STAT functions in mammary gland development

    PubMed Central

    Hughes, Katherine; Watson, Christine J.

    2012-01-01

    The signal transducer and activator of transcription (STAT) family of transcription factors have a spectrum of functions in mammary gland development. In some cases these roles parallel those of STATs in other organ systems, while in other instances the function of individual STATs in the mammary gland is specific to this tissue. In the immune system, STAT6 is associated with differentiation of T helper cells, while in the mammary gland, it has a fundamental role in the commitment of luminal epithelial cells to the alveolar lineage. STAT5A is required for the production of luminal progenitor cells from mammary stem cells and is essential for the differentiation of milk producing alveolar cells during pregnancy. By contrast, the initiation of regression following weaning heralds a dramatic and specific activation of STAT3, reflecting its pivotal role in the regulation of cell death and tissue remodeling during mammary involution. Although it has been demonstrated that STAT1 is regulated during a mammary developmental cycle, it is not yet determined whether it has a specific, non-redundant function. Thus, the mammary gland constitutes an unusual example of an adult organ in which different STATs are sequentially activated to orchestrate the processes of functional differentiation, cell death and tissue remodeling. PMID:24058764

  7. Cutaneous metastases of a mammary carcinoma in a llama.

    PubMed Central

    Leichner, T L; Turner, O; Mason, G L; Barrington, G M

    2001-01-01

    An 8-year-old, female llama was evaluated for nonhealing, ulcerative, cutaneous lesions, which also involved the mammary gland. Biopsies of the lesions distant from and within the mammary gland area revealed an aggressive carcinoma. The tumor was confirmed at necropsy to be a mammary gland adenocarcinoma with cutaneous metastasis. Images Figure 1. PMID:11265189

  8. Growth Hormone and Insulin-Like Growth Factor-I in the Transition from Normal Mammary Development to Preneoplastic Mammary Lesions

    PubMed Central

    Kleinberg, David L.; Wood, Teresa L.; Furth, Priscilla A.; Lee, Adrian V.

    2009-01-01

    Adult female mammary development starts at puberty and is controlled by tightly regulated cross-talk between a group of hormones and growth factors. Although estrogen is the initial driving force and is joined by luteal phase progesterone, both of these hormones require GH-induced IGF-I in the mammary gland in order to act. The same group of hormones, when experimentally perturbed, can lead to development of hyperplastic lesions and increase the chances, or be precursors, of mammary carcinoma. For example, systemic administration of GH or IGF-I causes mammary hyperplasia, and overproduction of IGF-I in transgenic animals can cause the development of usual or atypical hyperplasias and sometimes carcinoma. Although studies have clearly demonstrated the transforming potential of both GH and IGF-I receptor in cell culture and in animals, debate remains as to whether their main role is actually instructive or permissive in progression to cancer in vivo. Genetic imprinting has been shown to occur in precursor lesions as early as atypical hyperplasia in women. Thus, the concept of progression from normal development to cancer through precursor lesions sensitive to hormones and growth factors discussed above is gaining support in humans as well as in animal models. Indeed, elevation of estrogen receptor, GH, IGF-I, and IGF-I receptor during progression suggests a role for these pathways in this process. New agents targeting the GH/IGF-I axis may provide a novel means to block formation and progression of precursor lesions to overt carcinoma. A novel somatostatin analog has recently been shown to prevent mammary development in rats via targeted IGF-I action inhibition at the mammary gland. Similarly, pegvisomant, a GH antagonist, and other IGF-I antagonists such as IGF binding proteins 1 and 5 also block mammary gland development. It is, therefore, possible that inhibition of IGF-I action, or perhaps GH, in the mammary gland may eventually play a role in breast cancer

  9. Runx2 contributes to the regenerative potential of the mammary epithelium.

    PubMed

    Ferrari, Nicola; Riggio, Alessandra I; Mason, Susan; McDonald, Laura; King, Ayala; Higgins, Theresa; Rosewell, Ian; Neil, James C; Smalley, Matthew J; Sansom, Owen J; Morris, Joanna; Cameron, Ewan R; Blyth, Karen

    2015-10-22

    Although best known for its role in bone development and associated structures the transcription factor RUNX2 is expressed in a wide range of lineages, including those of the mammary gland. Previous studies have indicated that Runx2 can regulate aspects of mammary cell function and influence the properties of cancer cells. In this study we investigate the role of Runx2 in the mammary stem/progenitor population and its relationship with WNT signalling. Results show that RUNX2 protein is differentially expressed throughout embryonic and adult development of the murine mammary gland with high levels of expression in mammary stem-cell enriched cultures. Importantly, functional analysis reveals a role for Runx2 in mammary stem/progenitor cell function in in vitro and in vivo regenerative assays. Furthermore, RUNX2 appears to be associated with WNT signalling in the mammary epithelium and is specifically upregulated in mouse models of WNT-driven breast cancer. Overall our studies reveal a novel function for Runx2 in regulating mammary epithelial cell regenerative potential, possibly acting as a downstream target of WNT signalling.

  10. Runx2 contributes to the regenerative potential of the mammary epithelium

    PubMed Central

    Ferrari, Nicola; Riggio, Alessandra I.; Mason, Susan; McDonald, Laura; King, Ayala; Higgins, Theresa; Rosewell, Ian; Neil, James C.; Smalley, Matthew J.; Sansom, Owen J.; Morris, Joanna; Cameron, Ewan R.; Blyth, Karen

    2015-01-01

    Although best known for its role in bone development and associated structures the transcription factor RUNX2 is expressed in a wide range of lineages, including those of the mammary gland. Previous studies have indicated that Runx2 can regulate aspects of mammary cell function and influence the properties of cancer cells. In this study we investigate the role of Runx2 in the mammary stem/progenitor population and its relationship with WNT signalling. Results show that RUNX2 protein is differentially expressed throughout embryonic and adult development of the murine mammary gland with high levels of expression in mammary stem-cell enriched cultures. Importantly, functional analysis reveals a role for Runx2 in mammary stem/progenitor cell function in in vitro and in vivo regenerative assays. Furthermore, RUNX2 appears to be associated with WNT signalling in the mammary epithelium and is specifically upregulated in mouse models of WNT-driven breast cancer. Overall our studies reveal a novel function for Runx2 in regulating mammary epithelial cell regenerative potential, possibly acting as a downstream target of WNT signalling. PMID:26489514

  11. Mammary Duct Ectasia

    MedlinePlus

    ... tenderness or inflammation of the clogged duct (periductal mastitis). Mammary duct ectasia most often occurs in women ... that's turned inward (inverted) A bacterial infection called mastitis also may develop in the affected milk duct, ...

  12. The male mammary gland: a target for the xenoestrogen bisphenol A

    PubMed Central

    Vandenberg, Laura N; Schaeberle, Cheryl M.; Rubin, Beverly S.; Sonnenschein, Carlos; Soto, Ana M.

    2014-01-01

    Males of some strains of mice retain their mammary epithelium even in the absence of nipples. Here, we have characterized the mammary gland in male CD-1 mice both in whole mounts and histological sections. We also examined the effects of bisphenol A (BPA), an estrogen mimic that alters development of the female mouse mammary gland. BPA was administered at a range of environmentally relevant doses (0.25 – 250 μg/kg/day) to pregnant and lactating mice and then the mammary glands of male offspring were examined at several periods in adulthood. We observed age- and dose-specific effects on mammary gland morphology, indicating that perinatal BPA exposures alter the male mammary gland in adulthood. These results may provide insight into gynecomastia, the most common male breast disease in humans, where proliferation of the mammary epithelium leads to breast enlargement. PMID:23348055

  13. Sequencing the transcriptome of milk production: milk trumps mammary tissue

    PubMed Central

    2013-01-01

    Background Studies of normal human mammary gland development and function have mostly relied on cell culture, limited surgical specimens, and rodent models. Although RNA extracted from human milk has been used to assay the mammary transcriptome non-invasively, this assay has not been adequately validated in primates. Thus, the objectives of the current study were to assess the suitability of lactating rhesus macaques as a model for lactating humans and to determine whether RNA extracted from milk fractions is representative of RNA extracted from mammary tissue for the purpose of studying the transcriptome of milk-producing cells. Results We confirmed that macaque milk contains cytoplasmic crescents and that ample high-quality RNA can be obtained for sequencing. Using RNA sequencing, RNA extracted from macaque milk fat and milk cell fractions more accurately represented RNA from mammary epithelial cells (cells that produce milk) than did RNA from whole mammary tissue. Mammary epithelium-specific transcripts were more abundant in macaque milk fat, whereas adipose or stroma-specific transcripts were more abundant in mammary tissue. Functional analyses confirmed the validity of milk as a source of RNA from milk-producing mammary epithelial cells. Conclusions RNA extracted from the milk fat during lactation accurately portrayed the RNA profile of milk-producing mammary epithelial cells in a non-human primate. However, this sample type clearly requires protocols that minimize RNA degradation. Overall, we validated the use of RNA extracted from human and macaque milk and provided evidence to support the use of lactating macaques as a model for human lactation. PMID:24330573

  14. Sequencing the transcriptome of milk production: milk trumps mammary tissue.

    PubMed

    Lemay, Danielle G; Hovey, Russell C; Hartono, Stella R; Hinde, Katie; Smilowitz, Jennifer T; Ventimiglia, Frank; Schmidt, Kimberli A; Lee, Joyce W S; Islas-Trejo, Alma; Silva, Pedro Ivo; Korf, Ian; Medrano, Juan F; Barry, Peter A; German, J Bruce

    2013-12-12

    Studies of normal human mammary gland development and function have mostly relied on cell culture, limited surgical specimens, and rodent models. Although RNA extracted from human milk has been used to assay the mammary transcriptome non-invasively, this assay has not been adequately validated in primates. Thus, the objectives of the current study were to assess the suitability of lactating rhesus macaques as a model for lactating humans and to determine whether RNA extracted from milk fractions is representative of RNA extracted from mammary tissue for the purpose of studying the transcriptome of milk-producing cells. We confirmed that macaque milk contains cytoplasmic crescents and that ample high-quality RNA can be obtained for sequencing. Using RNA sequencing, RNA extracted from macaque milk fat and milk cell fractions more accurately represented RNA from mammary epithelial cells (cells that produce milk) than did RNA from whole mammary tissue. Mammary epithelium-specific transcripts were more abundant in macaque milk fat, whereas adipose or stroma-specific transcripts were more abundant in mammary tissue. Functional analyses confirmed the validity of milk as a source of RNA from milk-producing mammary epithelial cells. RNA extracted from the milk fat during lactation accurately portrayed the RNA profile of milk-producing mammary epithelial cells in a non-human primate. However, this sample type clearly requires protocols that minimize RNA degradation. Overall, we validated the use of RNA extracted from human and macaque milk and provided evidence to support the use of lactating macaques as a model for human lactation.

  15. Mammary gland tumors in captive African hedgehogs.

    PubMed

    Raymond, J T; Gerner, M

    2000-04-01

    From December 1995 to July 1999, eight mammary gland tumors were diagnosed in eight adult captive female African hedgehogs (Atelerix albiventris). The tumors presented as single or multiple subcutaneous masses along the cranial or caudal abdomen that varied in size for each hedgehog. Histologically, seven of eight (88%) mammary gland tumors were malignant. Tumors were classified as solid (4 cases), tubular (2 cases), and papillary (2 cases). Seven tumors had infiltrated into the surrounding stroma and three tumors had histologic evidence of neoplastic vascular invasion. Three hedgehogs had concurrent neoplasms. These are believed to be the first reported cases of mammary gland tumors in African hedgehogs.

  16. A novel approach for the generation of genetically modified mammary epithelial cell cultures yields new insights into TGFβ signaling in the mammary gland

    PubMed Central

    2010-01-01

    Introduction Molecular dissection of the signaling pathways that underlie complex biological responses in the mammary epithelium is limited by the difficulty of propagating large numbers of mouse mammary epithelial cells, and by the inability of ribonucleic acid interference-based knockdown approaches to fully ablate gene function. Here we describe a method for the generation of conditionally immortalized mammary epithelial cells with defined genetic defects, and we show how such cells can be used to investigate complex signal transduction processes using the transforming growth factor beta (TGFβ)/Smad pathway as an example. Methods We intercrossed the previously described H-2Kb-tsA58 transgenic mouse (Immortomouse), which expresses a temperature-sensitive mutant of the simian virus-40 large T-antigen (tsTAg), with mice of differing Smad genotypes. Conditionally immortalized mammary epithelial cell cultures were derived from the virgin mammary glands of offspring of these crosses and were used to assess the Smad dependency of different biological responses to TGFβ. Results IMECs could be propagated indefinitely at permissive temperatures and had a stable epithelial phenotype, resembling primary mammary epithelial cells with respect to several criteria, including responsiveness to TGFβ. Using this panel of cells, we demonstrated that Smad3, but not Smad2, is necessary for TGFβ-induced apoptotic, growth inhibitory and epithelial-to-mesenchymal transition responses, whereas either Smad2 or Smad3 can support TGFβ-induced invasion as long as a threshold level of total Smad is exceeded. Conclusions The present work demonstrates the practicality and utility of generating conditionally immortalized mammary epithelial cell lines from genetically modified Immortomice for detailed investigation of complex signaling pathways in the mammary epithelium. PMID:20942910

  17. Point-of-care ultrasonography by pediatric emergency medicine physicians.

    PubMed

    Marin, Jennifer R; Lewiss, Resa E

    2015-04-01

    Emergency physicians have used point-of-care ultrasonography since the 1990 s. Pediatric emergency medicine physicians have more recently adopted this technology. Point-of-care ultrasonography is used for various scenarios, particularly the evaluation of soft tissue infections or blunt abdominal trauma and procedural guidance. To date, there are no published statements from national organizations specifically for pediatric emergency physicians describing the incorporation of point-of-care ultrasonography into their practice. This document outlines how pediatric emergency departments may establish a formal point-of-care ultrasonography program. This task includes appointing leaders with expertise in point-of-care ultrasonography, effectively training and credentialing physicians in the department, and providing ongoing quality assurance reviews. Copyright © 2015 by the American Academy of Pediatrics.

  18. Mammary microbiota of dairy ruminants: fact or fiction?

    PubMed

    Rainard, Pascal

    2017-04-17

    Explorations of how the complex microbial communities that inhabit different body sites might contribute to health and disease have prompted research on the ways the harmonious relationship between a host and its microbiota could be used to keep animals healthy in their production conditions. In particular, there is a growing interest in the bacterial signatures that can be found in the milk of healthy or mastitic dairy cows. The concept of sterility of the healthy mammary gland of dairy ruminants has been challenged by the results of studies using bacterial DNA-based methodology. The newly obtained data have led to the concept of the intramammary microbiota composed of a complex community of diverse bacteria. Accordingly, mammary gland infections are not mere infections by a bacterial pathogen, but the consequence of mammary dysbiosis. This article develops the logical implications of this paradigm shift and shows how this concept is incompatible with current knowledge concerning the innate and adaptive immune system of the mammary gland of dairy ruminants. It also highlights how the concept of mammary microbiota clashes with results of experimental infections induced under controlled conditions or large field experiments that demonstrated the efficacy of the current mastitis control measures.

  19. STAT signaling in mammary gland differentiation, cell survival and tumorigenesis.

    PubMed

    Haricharan, S; Li, Y

    2014-01-25

    The mammary gland is a unique organ that undergoes extensive and profound changes during puberty, menstruation, pregnancy, lactation and involution. The changes that take place during puberty involve large-scale proliferation and invasion of the fat-pad. During pregnancy and lactation, the mammary cells are exposed to signaling pathways that inhibit apoptosis, induce proliferation and invoke terminal differentiation. Finally, during involution the mammary gland is exposed to milk stasis, programmed cell death and stromal reorganization to clear the differentiated milk-producing cells. Not surprisingly, the signaling pathways responsible for bringing about these changes in breast cells are often subverted during the process of tumorigenesis. The STAT family of proteins is involved in every stage of mammary gland development, and is also frequently implicated in breast tumorigenesis. While the roles of STAT3 and STAT5 during mammary gland development and tumorigenesis are well studied, others members, e.g. STAT1 and STAT6, have only recently been observed to play a role in mammary gland biology. Continued investigation into the STAT protein network in the mammary gland will likely yield new biomarkers and risk factors for breast cancer, and may also lead to novel prophylactic or therapeutic strategies against breast cancer. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. STAT signaling in mammary gland differentiation, cell survival and tumorigenesis

    PubMed Central

    Haricharan, S; Li, Y

    2013-01-01

    The mammary gland is a unique organ that undergoes extensive and profound changes during puberty, menstruation, pregnancy, lactation and involution. The changes that take place during puberty involve large-scale proliferation and invasion of the fat-pad. During pregnancy and lactation, the mammary cells are exposed to signaling pathways that inhibit apoptosis, induce proliferation and invoke terminal differentiation. Finally, during involution the mammary gland is exposed to milk stasis, programed cell death and stromal reorganization to clear the differentiated milk-producing cells. Not surprisingly, the signaling pathways responsible for bringing about these changes in breast cells are often subverted during the process of tumorigenesis. The STAT family of proteins is involved in every stage of mammary gland development, and is also frequently implicated in breast tumorigenesis. While the roles of STAT3 and STAT5 during mammary gland development and tumorigenesis are well studied, others members, e.g. STAT1 and STAT6, have only recently been observed to play a role in mammary gland biology. Continued investigation into the STAT protein network in the mammary gland will likely yield new biomarkers and risk factors for breast cancer, and may also lead to novel prophylactic or therapeutic strategies against breast cancer. PMID:23541951

  1. Leptin expression in human mammary epithelial cells and breast milk.

    PubMed

    Smith-Kirwin, S M; O'Connor, D M; De Johnston, J; Lancey, E D; Hassink, S G; Funanage, V L

    1998-05-01

    Leptin has recently been shown to be produced by the human placenta and potentially plays a role in fetal and neonatal growth. Many functions of the placenta are replaced by the mammary gland in terms of providing critical growth factors for the newborn. In this study, we show that leptin is produced by human mammary epithelial cells as revealed by RT/PCR analysis of total RNA from mammary gland and immunohistochemical staining of breast tissue, cultured mammary epithelial cells, and secretory epithelial cells present in human milk. We also verify that immunoreactive leptin is present in whole milk at 30- to 150-fold higher concentrations than skim milk. We propose that leptin is secreted by mammary epithelial cells in milk fat globules, which partition into the lipid portion of breast milk.

  2. The Type 7 Serotonin Receptor, 5-HT7, Is Essential in the Mammary Gland for Regulation of Mammary Epithelial Structure and Function

    PubMed Central

    Pai, Vaibhav P.; Hernandez, Laura L.; Stull, Malinda A.; Horseman, Nelson D.

    2015-01-01

    Autocrine-paracrine activity of serotonin (5-hydroxytryptamine, 5-HT) is a crucial homeostatic parameter in mammary gland development during lactation and involution. Published studies suggested that the 5-HT7 receptor type was important for mediating several effects of 5-HT in the mammary epithelium. Here, using 5-HT7 receptor-null (HT7KO) mice we attempt to understand the role of this receptor in mediating 5-HT actions within the mammary gland. We demonstrate for the first time that HT7KO dams are inefficient at sustaining their pups. Histologically, the HT7KO mammary epithelium shows a significant deviation from the normal secretory epithelium in morphological architecture, reduced secretory vesicles, and numerous multinucleated epithelial cells with atypically displaced nuclei, during lactation. Mammary epithelial cells in HT7KO dams also display an inability to transition from lactation to involution as normally seen by transition from a columnar to a squamous cell configuration, along with alveolar cell apoptosis and cell shedding. Our results show that 5-HT7 is required for multiple actions of 5-HT in the mammary glands including core functions that contribute to changes in cell shape and cell turnover, as well as specialized secretory functions. Understanding these actions may provide new interventions to improve lactation performance and treat diseases such as mastitis and breast cancer. PMID:25664318

  3. Single-cell RNA-Seq reveals cell heterogeneity and hierarchy within mouse mammary epithelia.

    PubMed

    Sun, Heng; Miao, Zhengqiang; Zhang, Xin; Chan, Un In; Su, Sek Man; Guo, Sen; Wong, Chris Koon Ho; Xu, Xiaoling; Deng, Chu-Xia

    2018-06-01

    The mammary gland is very intricately and well organized into distinct tissues, including epithelia, endothelia, adipocytes, and stromal and immune cells. Many mammary gland diseases, such as breast cancer, arise from abnormalities in the mammary epithelium, which is mainly composed of two distinct lineages, the basal and luminal cells. Because of the limitation of traditional transcriptome analysis of bulk mammary cells, the hierarchy and heterogeneity of mammary cells within these two lineages remain unclear. To this end, using single-cell RNA-Seq coupled with FACS analysis and principal component analysis, we determined gene expression profiles of mammary epithelial cells of virgin and pregnant mice. These analyses revealed a much higher heterogeneity among the mammary cells than has been previously reported and enabled cell classification into distinct subgroups according to signature gene markers present in each group. We also identified and verified a rare CDH5 + cell subpopulation within a basal cell lineage as quiescent mammary stem cells (MaSCs). Moreover, using pseudo-temporal analysis, we reconstructed the developmental trajectory of mammary epithelia and uncovered distinct changes in gene expression and in biological functions of mammary cells along the developmental process. In conclusion, our work greatly refines the resolution of the cellular hierarchy in developing mammary tissues. The discovery of CDH5 + cells as MaSCs in these tissues may have implications for our understanding of the initiation, development, and pathogenesis of mammary tumors. © 2018 Sun et al.

  4. Growth hormone mRNA in mammary gland tumors of dogs and cats.

    PubMed Central

    Mol, J A; van Garderen, E; Selman, P J; Wolfswinkel, J; Rijinberk, A; Rutteman, G R

    1995-01-01

    We have shown recently that in the dog progestin administration results in mammary production of immunoreactive growth hormone (GH). At present we demonstrate the expression of the gene encoding GH in the mammary gland of dogs and cats using reverse-transcriptase PCR. GH mRNA was found in the great majority of normal mammary tissues as well as benign and malignant mammary tumors of the dog and was associated with the presence of immunoreactive GH in cryostat sections. The mammary PCR product proved to be identical to that of the pituitary. The highest expression levels were found after prolonged treatment with progestins. In carcinomas GH mRNA was also found in progesterone receptor-negative tissue samples, indicating that after malignant transformation GH gene expression may become progestin independent. GH mRNA was also present in mammary tissues of cats with progestin-induced fibroadenomatous changes. It is concluded that GH gene expression occurs in normal, hyperplastic, and neoplastic mammary tissue of the dog. The expression in normal tissue is stimulated by progestins and might mediate the progestin-stimulated development of canine mammary tumors. The demonstration of progestin-stimulated GH expression in mammary tissue of cats indicates that the phenomenon is more generalized among mammals. Images PMID:7738169

  5. Mammary fibroadenomatous hyperplasia in a male cat.

    PubMed

    Mayayo, Saray Lorna; Bo, Stefano; Pisu, Maria Carmela

    2018-01-01

    Mammary fibroadenomatous hyperplasia (MFH) is a benign pathology characterised by extensive proliferation of the ductal epithelium and mammary stroma. It typically occurs in young female cats, and seems to result from hypersensitivity to progesterone. A 2-year-old entire male European Shorthair cat presented to the veterinary clinic with enlargement of several mammary glands, which had developed within the previous 10 days. There was no prior administration of progestin in the cat's medical history. Diagnostic tests were performed to assess the basal progesterone concentration and the concentration after stimulation with gonadotropin-releasing hormone, which ruled out the presence of functional ovarian tissue. Histological examination of the testes excluded hormone-secreting testicular tumours. Histological examination of the mammary gland confirmed the diagnosis of MFH. Treatment was started with aglepristone, a selective competitor for progesterone receptors, administered subcutaneously at 15 mg/kg at days 1, 2, 8 and 15. A reduction in the size of the mammary glands was evident 6 days after the first administration, with complete remission observed after 4 weeks. To the best of our knowledge, this is the first full report of MFH in a male cat. Although the origin of the progestins responsible for MFH in this case could not be confirmed, in the light of the diagnostic tests performed and the results obtained, accidental contact with hormone-like substances seems to be the only plausible explanation for the cat's clinical signs. Inhibitor therapy was successful.

  6. Folic Acid Supplementation Promotes Mammary Tumor Progression in a Rat Model

    PubMed Central

    Deghan Manshadi, Shaidah; Ishiguro, Lisa; Sohn, Kyoung-Jin; Medline, Alan; Renlund, Richard; Croxford, Ruth; Kim, Young-In

    2014-01-01

    Folic acid supplementation may prevent the development of cancer in normal tissues but may promote the progression of established (pre)neoplastic lesions. However, whether or not folic acid supplementation can promote the progression of established (pre)neoplastic mammary lesions is unknown. This is a critically important issue because breast cancer patients and survivors in North America are likely exposed to high levels of folic acid owing to folic acid fortification and widespread supplemental use after cancer diagnosis. We investigated whether folic acid supplementation can promote the progression of established mammary tumors. Female Sprague-Dawley rats were placed on a control diet and mammary tumors were initiated with 7,12-dimethylbenza[a]anthracene at puberty. When the sentinel tumor reached a predefined size, rats were randomized to receive a diet containing the control, 2.5x, 4x, or 5x supplemental levels of folic acid for up to 12 weeks. The sentinel mammary tumor growth was monitored weekly. At necropsy, the sentinel and all other mammary tumors were analyzed histologically. The effect of folic acid supplementation on the expression of proteins involved in proliferation, apoptosis, and mammary tumorigenesis was determined in representative sentinel adenocarcinomas. Although no clear dose-response relationship was observed, folic acid supplementation significantly promoted the progression of the sentinel mammary tumors and was associated with significantly higher sentinel mammary tumor weight and volume compared with the control diet. Furthermore, folic acid supplementation was associated with significantly higher weight and volume of all mammary tumors. The most significant and consistent mammary tumor-promoting effect was observed with the 2.5x supplemental level of folic acid. Folic acid supplementation was also associated with an increased expression of BAX, PARP, and HER2. Our data suggest that folic acid supplementation may promote the progression

  7. Development of novel murine mammary imaging windows to examine wound healing effects on leukocyte trafficking in mammary tumors with intravital imaging

    PubMed Central

    Sobolik, Tammy; Su, Ying-Jun; Ashby, Will; Schaffer, David K.; Wells, Sam; Wikswo, John P.; Zijlstra, Andries; Richmond, Ann

    2016-01-01

    ABSTRACT We developed mammary imaging windows (MIWs) to evaluate leukocyte infiltration and cancer cell dissemination in mouse mammary tumors imaged by confocal microscopy. Previous techniques relied on surgical resection of a skin flap to image the tumor microenvironment restricting imaging time to a few hours. Utilization of mammary imaging windows offers extension of intravital imaging of the tumor microenvironment. We have characterized strengths and identified some previously undescribed potential weaknesses of MIW techniques. Through iterative enhancements of a transdermal portal we defined conditions for improved quality and extended confocal imaging time for imaging key cell-cell interactions in the tumor microenvironment. PMID:28243517

  8. Development of novel murine mammary imaging windows to examine wound healing effects on leukocyte trafficking in mammary tumors with intravital imaging.

    PubMed

    Sobolik, Tammy; Su, Ying-Jun; Ashby, Will; Schaffer, David K; Wells, Sam; Wikswo, John P; Zijlstra, Andries; Richmond, Ann

    2016-01-01

    We developed mammary imaging windows (MIWs) to evaluate leukocyte infiltration and cancer cell dissemination in mouse mammary tumors imaged by confocal microscopy. Previous techniques relied on surgical resection of a skin flap to image the tumor microenvironment restricting imaging time to a few hours. Utilization of mammary imaging windows offers extension of intravital imaging of the tumor microenvironment. We have characterized strengths and identified some previously undescribed potential weaknesses of MIW techniques. Through iterative enhancements of a transdermal portal we defined conditions for improved quality and extended confocal imaging time for imaging key cell-cell interactions in the tumor microenvironment.

  9. Genomic and Phenomic Study of Mammary Pathogenic Escherichia coli

    PubMed Central

    Blum, Shlomo E.; Heller, Elimelech D.; Sela, Shlomo; Elad, Daniel; Edery, Nir; Leitner, Gabriel

    2015-01-01

    Escherichia coli is a major etiological agent of intra-mammary infections (IMI) in cows, leading to acute mastitis and causing great economic losses in dairy production worldwide. Particular strains cause persistent IMI, leading to recurrent mastitis. Virulence factors of mammary pathogenic E. coli (MPEC) involved pathogenesis of mastitis as well as those differentiating strains causing acute or persistent mastitis are largely unknown. This study aimed to identify virulence markers in MPEC through whole genome and phenome comparative analysis. MPEC strains causing acute (VL2874 and P4) or persistent (VL2732) mastitis were compared to an environmental strain (K71) and to the genomes of strains representing different E. coli pathotypes. Intra-mammary challenge in mice confirmed experimentally that the strains studied here have different pathogenic potential, and that the environmental strain K71 is non-pathogenic in the mammary gland. Analysis of whole genome sequences and predicted proteomes revealed high similarity among MPEC, whereas MPEC significantly differed from the non-mammary pathogenic strain K71, and from E. coli genomes from other pathotypes. Functional features identified in MPEC genomes and lacking in the non-mammary pathogenic strain were associated with synthesis of lipopolysaccharide and other membrane antigens, ferric-dicitrate iron acquisition and sugars metabolism. Features associated with cytotoxicity or intra-cellular survival were found specifically in the genomes of strains from severe and acute (VL2874) or persistent (VL2732) mastitis, respectively. MPEC genomes were relatively similar to strain K-12, which was subsequently shown here to be possibly pathogenic in the mammary gland. Phenome analysis showed that the persistent MPEC was the most versatile in terms of nutrients metabolized and acute MPEC the least. Among phenotypes unique to MPEC compared to the non-mammary pathogenic strain were uric acid and D-serine metabolism. This study

  10. Keeping abreast of the mammary epithelial hierarchy and breast tumorigenesis.

    PubMed

    Visvader, Jane E

    2009-11-15

    The epithelium of the mammary gland exists in a highly dynamic state, undergoing dramatic morphogenetic changes during puberty, pregnancy, lactation, and regression. The recent identification of stem and progenitor populations in mouse and human mammary tissue has provided evidence that the mammary epithelium is organized in a hierarchical manner. Characterization of these normal epithelial subtypes is an important step toward understanding which cells are predisposed to oncogenesis. This review summarizes progress in the field toward defining constituent cells and key molecular regulators of the mammary epithelial hierarchy. Potential relationships between normal epithelial populations and breast tumor subtypes are discussed, with implications for understanding the cellular etiology underpinning breast tumor heterogeneity.

  11. Role of ultrasonography in the management of twin gestation.

    PubMed

    Smith, Jessica; Treadwell, Marjorie C; Berman, Deborah R

    2018-06-01

    Twins represent 1%-2% of all pregnancies, yet continue to account for a disproportionate share of neonatal adverse events including neonatal intensive care admission, morbidity, and mortality. Ultrasonography is central to the proper diagnosis of the type of twinning. Ideally, ultrasonography is performed before 14 weeks of gestation to determine chorionicity and amnionicity. Correct identification of the chorionicity in a twin pregnancy facilitates proper counseling and management of the gestation, including ultrasonography follow-up. Herein, the different types of twinning are reviewed, together with the implications for ultrasonography monitoring of each specific type of twin gestation. © 2018 International Federation of Gynecology and Obstetrics.

  12. Mechanical strain induces involution-associated events in mammary epithelial cells

    PubMed Central

    Quaglino, Ana; Salierno, Marcelo; Pellegrotti, Jesica; Rubinstein, Natalia; Kordon, Edith C

    2009-01-01

    Background Shortly after weaning, a complex multi-step process that leads to massive epithelial apoptosis is triggered by tissue local factors in the mouse mammary gland. Several reports have demonstrated the relevance of mechanical stress to induce adaptive responses in different cell types. Interestingly, these signaling pathways also participate in mammary gland involution. Then, it has been suggested that cell stretching caused by milk accumulation after weaning might be the first stimulus that initiates the complete remodeling of the mammary gland. However, no previous report has demonstrated the impact of mechanical stress on mammary cell physiology. To address this issue, we have designed a new practical device that allowed us to evaluate the effects of radial stretching on mammary epithelial cells in culture. Results We have designed and built a new device to analyze the biological consequences of applying mechanical stress to cells cultured on flexible silicone membranes. Subsequently, a geometrical model that predicted the percentage of radial strain applied to the elastic substrate was developed. By microscopic image analysis, the adjustment of these calculations to the actual strain exerted on the attached cells was verified. The studies described herein were all performed in the HC11 non-tumorigenic mammary epithelial cell line, which was originated from a pregnant BALB/c mouse. In these cells, as previously observed in other tissue types, mechanical stress induced ERK1/2 phosphorylation and c-Fos mRNA and protein expression. In addition, we found that mammary cell stretching triggered involution associated cellular events as Leukemia Inhibitory Factor (LIF) expression induction, STAT3 activation and AKT phosphorylation inhibition. Conclusion Here, we show for the first time, that mechanical strain is able to induce weaning-associated events in cultured mammary epithelial cells. These results were obtained using a new practical and affordable device

  13. Mammary fibroadenomatous hyperplasia in a male cat

    PubMed Central

    Mayayo, Saray Lorna; Bo, Stefano; Pisu, Maria Carmela

    2018-01-01

    Case summary Mammary fibroadenomatous hyperplasia (MFH) is a benign pathology characterised by extensive proliferation of the ductal epithelium and mammary stroma. It typically occurs in young female cats, and seems to result from hypersensitivity to progesterone. A 2-year-old entire male European Shorthair cat presented to the veterinary clinic with enlargement of several mammary glands, which had developed within the previous 10 days. There was no prior administration of progestin in the cat’s medical history. Diagnostic tests were performed to assess the basal progesterone concentration and the concentration after stimulation with gonadotropin-releasing hormone, which ruled out the presence of functional ovarian tissue. Histological examination of the testes excluded hormone-secreting testicular tumours. Histological examination of the mammary gland confirmed the diagnosis of MFH. Treatment was started with aglepristone, a selective competitor for progesterone receptors, administered subcutaneously at 15 mg/kg at days 1, 2, 8 and 15. A reduction in the size of the mammary glands was evident 6 days after the first administration, with complete remission observed after 4 weeks. Relevance and novel information To the best of our knowledge, this is the first full report of MFH in a male cat. Although the origin of the progestins responsible for MFH in this case could not be confirmed, in the light of the diagnostic tests performed and the results obtained, accidental contact with hormone-like substances seems to be the only plausible explanation for the cat’s clinical signs. Inhibitor therapy was successful. PMID:29568542

  14. Stromal and Epithelial Caveolin-1 Both Confer a Protective Effect Against Mammary Hyperplasia and Tumorigenesis

    PubMed Central

    Williams, Terence M.; Sotgia, Federica; Lee, Hyangkyu; Hassan, Ghada; Di Vizio, Dolores; Bonuccelli, Gloria; Capozza, Franco; Mercier, Isabelle; Rui, Hallgeir; Pestell, Richard G.; Lisanti, Michael P.

    2006-01-01

    Here, we investigate the role of caveolin-1 (Cav-1) in breast cancer onset and progression, with a focus on epithelial-stromal interactions, ie, the tumor microenvironment. Cav-1 is highly expressed in adipocytes and is abundant in mammary fat pads (stroma), but it remains unknown whether loss of Cav-1 within mammary stromal cells affects the differentiated state of mammary epithelia via paracrine signaling. To address this issue, we characterized the development of the mammary ductal system in Cav-1−/− mice and performed a series of mammary transplant studies, using both wild-type and Cav-1−/− mammary fat pads. Cav-1−/− mammary epithelia were hyperproliferative in vivo, with dramatic increases in terminal end bud area and mammary ductal thickness as well as increases in bromodeoxyuridine incorporation, extracellular signal-regulated kinase-1/2 hyperactivation, and up-regulation of STAT5a and cyclin D1. Consistent with these findings, loss of Cav-1 dramatically exacerbated mammary lobulo-alveolar hyperplasia in cyclin D1 Tg mice, whereas overexpression of Cav-1 caused reversion of this phenotype. Most importantly, Cav-1−/− mammary stromal cells (fat pads) promoted the growth of both normal mammary ductal epithelia and mammary tumor cells. Thus, Cav-1 expression in both epithelial and stromal cells provides a protective effect against mammary hyperplasia as well as mammary tumorigenesis. PMID:17071600

  15. Effects of rumen-undegradable protein on intake, performance, and mammary gland development in prepubertal and pubertal dairy heifers.

    PubMed

    Silva, A L; Detmann, E; Dijkstra, J; Pedroso, A M; Silva, L H P; Machado, A F; Sousa, F C; Dos Santos, G B; Marcondes, M I

    2018-04-04

    The objective of this study was to evaluate the influence of different amounts of rumen-undegradable protein (RUP) on intake, N balance, performance, mammary gland development, carcass traits, and hormonal status of Holstein heifers at different physiological stages (PS). Sixteen prepubertal (PRE) heifers (initial BW = 106 ± 7.6 kg; age = 4.3 ± 0.46 mo) and 16 pubertal (PUB) heifers (initial BW = 224 ± 7.9 kg; age = 12.6 ± 0.45 mo) were used in an experiment over a period of 84 d. Four diets with increasing RUP contents (38, 44, 51, and 57% of dietary crude protein) and heifers at 2 PS (PRE or PUB) were used in a 4 × 2 factorial arrangement of treatments in a completely randomized design. Throughout the experiment, 2 digestibility trials were performed over 5 consecutive days (starting at d 36 and 78) involving feed and ort sampling and spot collections of feces and urine. At d 0 and 83, body ultrasound images were obtained for real-time carcass trait evaluation. The mammary gland was ultrasonically scanned at d 0 and every 3 wk during the experiment. Blood samples were taken at d 0 and 84 to determine serum concentrations of progesterone, estrogen, insulin-like growth factor I (IGF-I), and insulin. No interaction between PS and the level of RUP was found for any trait. Apparent digestibility of dry matter, organic matter, and neutral detergent fiber corrected for ash and protein was not affected by RUP level but was lower for PRE compared with PUB heifers. Sorting against neutral detergent fiber corrected for ash and protein (tendency only) and for crude protein was greater for PUB than PRE heifers. Pubertal heifers had greater average daily gain (905 vs. 505 g/d) and N retention (25.9 vs. 12.5 g/d) than PRE heifers. In addition, average daily gain and N retention were greatest at 51% RUP of dietary protein. Mammary ultrasonography indicated no effects of RUP amounts on mammary gland composition, whereas PRE heifers had greater pixel values than PUB

  16. The Origin and Significance of Mammary Intraductal Foam Cells

    DTIC Science & Technology

    2005-09-01

    hematopoeitic origin developed in mammary tissue with both benign and malignant differentiation, depending on environmental cues. Progression of the cells...contribution of hematopoeitic precursors to the heterogeneity of cell types in benign and malignant mammary tissue.

  17. Ectodysplasin/NF-κB Promotes Mammary Cell Fate via Wnt/β-catenin Pathway

    PubMed Central

    Voutilainen, Maria; Lönnblad, Darielle; Shirokova, Vera; Elo, Teresa; Rysti, Elisa; Schmidt-Ullrich, Ruth; Schneider, Pascal; Mikkola, Marja L.

    2015-01-01

    Mammary gland development commences during embryogenesis with the establishment of a species typical number of mammary primordia on each flank of the embryo. It is thought that mammary cell fate can only be induced along the mammary line, a narrow region of the ventro-lateral skin running from the axilla to the groin. Ectodysplasin (Eda) is a tumor necrosis factor family ligand that regulates morphogenesis of several ectodermal appendages. We have previously shown that transgenic overexpression of Eda (K14-Eda mice) induces formation of supernumerary mammary placodes along the mammary line. Here, we investigate in more detail the role of Eda and its downstream mediator transcription factor NF-κB in mammary cell fate specification. We report that K14-Eda mice harbor accessory mammary glands also in the neck region indicating wider epidermal cell plasticity that previously appreciated. We show that even though NF-κB is not required for formation of endogenous mammary placodes, it is indispensable for the ability of Eda to induce supernumerary placodes. A genome-wide profiling of Eda-induced genes in mammary buds identified several Wnt pathway components as potential transcriptional targets of Eda. Using an ex vivo culture system, we show that suppression of canonical Wnt signalling leads to a dose-dependent inhibition of supernumerary placodes in K14-Eda tissue explants. PMID:26581094

  18. Luminal Progenitors Restrict Their Lineage Potential during Mammary Gland Development

    PubMed Central

    Rodilla, Veronica; Dasti, Alessandro; Huyghe, Mathilde; Lafkas, Daniel; Laurent, Cécile; Reyal, Fabien; Fre, Silvia

    2015-01-01

    The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used the expression of the Notch1 receptor, previously implicated in mammary gland development and tumorigenesis, to elucidate the hierarchical organization of mammary stem/progenitor cells by lineage tracing. We found that Notch1 expression identifies multipotent stem cells in the embryonic mammary bud, which progressively restrict their lineage potential during mammary ductal morphogenesis to exclusively generate an ERαneg luminal lineage postnatally. Importantly, our results show that Notch1-labelled cells represent the alveolar progenitors that expand during pregnancy and survive multiple successive involutions. This study reveals that postnatal luminal epithelial cells derive from distinct self-sustained lineages that may represent the cells of origin of different breast cancer subtypes. PMID:25688859

  19. Luminal progenitors restrict their lineage potential during mammary gland development.

    PubMed

    Rodilla, Veronica; Dasti, Alessandro; Huyghe, Mathilde; Lafkas, Daniel; Laurent, Cécile; Reyal, Fabien; Fre, Silvia

    2015-02-01

    The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used the expression of the Notch1 receptor, previously implicated in mammary gland development and tumorigenesis, to elucidate the hierarchical organization of mammary stem/progenitor cells by lineage tracing. We found that Notch1 expression identifies multipotent stem cells in the embryonic mammary bud, which progressively restrict their lineage potential during mammary ductal morphogenesis to exclusively generate an ERαneg luminal lineage postnatally. Importantly, our results show that Notch1-labelled cells represent the alveolar progenitors that expand during pregnancy and survive multiple successive involutions. This study reveals that postnatal luminal epithelial cells derive from distinct self-sustained lineages that may represent the cells of origin of different breast cancer subtypes.

  20. Mammary duct ectasia: a cause of bloody nipple discharge.

    PubMed Central

    Leung, Alexander K. C.; Kao, C. Pion

    2004-01-01

    We report a 13-year-old girl with bloody nipple discharge as a result of mammary duct ectasia. Our patient is the second reported case of mammary duct ectasia in a pubertal girl. Images Figure 1 PMID:15101674

  1. Metallothionein expression in canine and feline mammary and melanotic tumours.

    PubMed

    Dincer, Z; Jasani, B; Haywood, S; Mullins, J E; Fuentealba, I C

    2001-01-01

    Moderate to strong immunohistochemical metallothionein (MT) positivity (MT expression) is associated with a poor prognosis in some human tumours. The aim of this study was to determine MT expression in mammary tumours and cutaneous melanomas in dogs and cats. Canine (67) and feline (47) mammary tumours, and cutaneous melanomas (canine 40, feline 26) were immunolabelled with MT monoclonal antibody E9. The overall incidence of MT expression of these tumours was similar to that observed in various human neoplasms. However, a striking interspecies difference was detected. In dogs, MT expression occurred in 100% of benign and 57% of malignant mammary tumours. In cats, however, 30% of malignant mammary tumours expressed MT but benign mammary tumours and cases of fibroadenomatous hyperplasia did not. Moderate to strong MT immunoreactivity was detected in 30% of benign and 25% of malignant cutaneous melanomas in dogs, and in 6% of malignant melanomas in cats. The findings in feline mammary tumours resembled findings reported in human breast cancer, but the cause of tumour-associated MT expression is unknown. Studies are in progress to determine whether the MT state (apo [metal-free] or holo [metal-bound]) accounts for the paradoxical association of MT expression with individual types of tumours and the animal species in which they arise. Copyright Harcourt Publishers Ltd.

  2. A Spectrum of Monoclonal Antibodies Reactive with Human Mammary Tumor Cells

    NASA Astrophysics Data System (ADS)

    Colcher, D.; Horan Hand, P.; Nuti, M.; Schlom, J.

    1981-05-01

    Splenic lymphocytes of mice, immunized with membrane-enriched fractions of metastatic human mammary carcinoma tissues, were fused with the NS-1 non-immunoglobulin-secreting murine myeloma cell line. This resulted in the generation of hybridoma cultures secreting immunoglobulins reactive in solid-phase radioimmunoassays with extracts of metastatic mammary carcinoma cells from involved livers, but not with extracts of apparently normal human liver. As a result of further screening of immunoglobulin reactivities and double cloning of cultures, 11 monoclonal antibodies were chosen that demonstrated reactivities with human mammary tumor cells and not with apparently normal human tissues. These monoclonal antibodies could be placed into at least five major groups on the basis of their differential binding to the surface of various live human mammary tumor cells in culture, to extracts of mammary tumor tissues, or to tissue sections of mammary tumor cells studied by the immunoperoxidase technique. Whereas a spectrum of reactivities to mammary tumors was observed with the 11 monoclonal antibodies, no reactivity was observed to apparently normal cells of the following human tissues: breast, lymph node, lung, skin, testis, kidney, thymus, bone marrow, spleen, uterus, thyroid, intestine, liver, bladder, tonsils, stomach, prostate, and salivary gland. Several of the antibodies also demonstrated a ``pancarcinoma'' reactivity, showing binding to selected non-breast carcinomas. None of the monoclonal antibodies showed binding to purified ferritin or carcinoembryonic antigen. Monoclonal antibodies of all five major groups, however, demonstrated binding to human metastatic mammary carcinoma cells both in axillary lymph nodes and at distal sites.

  3. In vitro expansion of the mammary stem/progenitor cell population by xanthosinetreatment

    USDA-ARS?s Scientific Manuscript database

    Background: Mammary stem cells are critical for growth and maintenance of the mammary gland and therefore of considerable interest for improving productivity and efficiency of dairy animals. Xanthosine (Xs) treatment has been demonstrated to promote expansion of putative mammary stem cells in vivo ...

  4. Mammary blood flow regulation in the nursing rabbit

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Katz, M.; Creasy, R.K.

    Cardiac output and mammary blood flow distribution prior to and after suckling were studied in 10 nursing rabbits by means of radionuclide-labeled microspheres. Suckling was followed by a 5.8% rise in cardiac output and a 20.4% rise in mammary blood flow. Determinations of intraglandular blood flow distribution have shown that there was a 43% increase in blood flow to the glands suckled from as compared to a 22.7% rise to the contralateral untouched glands and a 4.9% rise in the remainder of untouched glands. The conclusion is that a local mechanism may be involved in the regulation of mammary bloodmore » flow in the nursing rabbit.« less

  5. Mammary stem cells have myoepithelial cell properties

    PubMed Central

    Prater, Michael D.; Petit, Valérie; Russell, I. Alasdair; Giraddi, Rajshekhar; Shehata, Mona; Menon, Suraj; Schulte, Reiner; Kalajzic, Ivo; Rath, Nicola; Olson, Michael F.; Metzger, Daniel; Faraldo, Marisa M.; Deugnier, Marie-Ange; Glukhova, Marina A.; Stingl, John

    2014-01-01

    Contractile myoepithelial cells dominate the basal layer of the mammary epithelium and are considered to be differentiated cells. However, we observe that up to 54% of single basal cells can form colonies when seeded into adherent culture in the presence of agents that disrupt acin-myosin interactions, and on average, 65% of the single-cell-derived basal colonies can repopulate a mammary gland when transplanted in vivo. This indicates that a high proportion of basal myoepithelial cells can give rise to a mammary repopulating unit (MRU). We demonstrate that myoepithelial cells, flow-sorted using 2 independent myoepithelial-specific reporter strategies, have MRU capacity. Using an inducible lineage tracing approach we follow the progeny of α-smooth muscle actin-expressing myoepithelial cells and show that they function as long-lived lineage-restricted stem cells in the virgin state and during pregnancy. PMID:25173976

  6. Bovine mammary stem cells: Cell biology meets production agriculture

    USDA-ARS?s Scientific Manuscript database

    Mammary stem cells (MaSC) provide for net growth, renewal and turnover of mammary epithelial cells, and are therefore potential targets for strategies to increase production efficiency. Appropriate regulation of MaSC can potentially benefit milk yield, persistency, dry period management and tissue ...

  7. Six1 expands the mouse mammary epithelial stem/progenitor cell pool and induces mammary tumors that undergo epithelial-mesenchymal transition

    PubMed Central

    McCoy, Erica L.; Iwanaga, Ritsuko; Jedlicka, Paul; Abbey, Nee-Shamo; Chodosh, Lewis A.; Heichman, Karen A.; Welm, Alana L.; Ford, Heide L.

    2009-01-01

    Six1 is a developmentally regulated homeoprotein with limited expression in most normal adult tissues and frequent misexpression in a variety of malignancies. Here we demonstrate, using a bitransgenic mouse model, that misexpression of human Six1 in adult mouse mammary gland epithelium induces tumors of multiple histological subtypes in a dose-dependent manner. The neoplastic lesions induced by Six1 had an in situ origin, showed diverse differentiation, and exhibited progression to aggressive malignant neoplasms, as is often observed in human carcinoma of the breast. Strikingly, the vast majority of Six1-induced tumors underwent an epithelial-mesenchymal transition (EMT) and expressed multiple targets of activated Wnt signaling, including cyclin D1. Interestingly, Six1 and cyclin D1 coexpression was found to frequently occur in human breast cancers and was strongly predictive of poor prognosis. We further show that Six1 promoted a stem/progenitor cell phenotype in the mouse mammary gland and in Six1-driven mammary tumors. Our data thus provide genetic evidence for a potent oncogenic role for Six1 in mammary epithelial neoplasia, including promotion of EMT and stem cell–like features. PMID:19726883

  8. Keratinocyte growth factor is a growth factor for mammary epithelium in vivo. The mammary epithelium of lactating rats is resistant to the proliferative action of keratinocyte growth factor.

    PubMed Central

    Ulich, T. R.; Yi, E. S.; Cardiff, R.; Yin, S.; Bikhazi, N.; Biltz, R.; Morris, C. F.; Pierce, G. F.

    1994-01-01

    Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor (FGF) family. KGF is secreted by stromal cells and affects epithelial but not mesenchymal cell proliferation. KGF injected intravenously was found to cause dramatic proliferation of mammary epithelium in the mammary glands of rats. KGF causes ductal neogenesis and intraductal epithelial hyperplasia but not lobular differentiation in nulliparous female rats. KGF causes ductal and lobular epithelial hyperplasia in male rats. KGF causes proliferation of ductal and acinar cells in the mammary glands of pregnant rats. On the other hand, the ductal epithelium of lactating postpartum rats is resistant to the proliferative action of KGF. The mammary glands of lactating rats did not express less KGF receptor mRNA than the glands of pregnant rats, suggesting that the resistance of the ductal epithelium to KGF during lactation is not related to KGF receptor mRNA down-regulation. The mammary glands of both pregnant and postpartum lactating rats express KGF mRNA with more KGF present in the glands of lactating rats. In conclusion, the KGF and KGF receptor genes are expressed in rat mammary glands and recombinant KGF is a potent growth factor for mammary epithelium. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8178937

  9. Isolation of Endoplasmic Reticulum Fractions from Mammary Epithelial Tissue.

    PubMed

    Chanat, Eric; Le Parc, Annabelle; Lahouassa, Hichem; Badaoui, Bouabid

    2016-06-01

    In the mammary glands of lactating animals, the mammary epithelial cells that surround the lumen of the acini produce and secrete copious amounts of milk. Functional differentiation of these mammary epithelial cells depends on the development of high-efficiency secretory pathways, notably for protein and lipid secretion. Protein secretion is a fundamental process common to all animal cells that involves a subset of cellular organelles, including the endoplasmic reticulum and the Golgi apparatus. In contrast, en masse secretion of triglycerides and cholesterol esters in the form of milk fat globules is a unique feature of the mammary epithelial cell. Cytoplasmic lipid droplets, the intracellular precursors of milk fat globules, originate from the endoplasmic reticulum, as do most milk-specific proteins. This organelle is therefore pivotal in the biogenesis of milk components. Fractionation of the cell into its subcellular parts is an approach that has proven very powerful for understanding organelle function and for studying the specific role of an organelle in a given cell activity. Here we describe a method for the purification of both smooth and rough microsomes, the membrane-bound endoplasmic reticulum fragments that form from endoplasmic reticulum domains when cells are broken up, from mammary gland tissue at lactation.

  10. Autocrine-paracrine regulation of the mammary gland.

    PubMed

    Weaver, S R; Hernandez, L L

    2016-01-01

    The mammary gland has a remarkable capacity for regulation at a local level, particularly with respect to its main function: milk secretion. Regulation of milk synthesis has significant effects on animal and human health, at the level of both the mother and the neonate. Control by the mammary gland of its essential function, milk synthesis, is an evolutionary necessity and is therefore tightly regulated at a local level. For at least the last 60 yr, researchers have been interested in elucidating the mechanisms underpinning the mammary gland's ability to self-regulate, largely without the influence from systemic hormones or signals. By the 1960s, scientists realized the importance of milk removal in the capacity of the gland to produce milk and that the dynamics of this removal, including emptying of the alveolar spaces and frequency of milking, were controlled locally as opposed to traditional systemic hormonal regulation. Using both in vitro systems and various mammalian species, including goats, marsupials, humans, and dairy cows, it has been demonstrated that the mammary gland is largely self-regulating in its capacity to support the young, which is the evolutionary basis for milk production. Local control occurs at the level of the mammary epithelial cell through pressure and stretching negative-feedback mechanisms, and also in an autocrine fashion through bioactive factors within the milk which act as inhibitors, regulating milk secretion within the alveoli themselves. It is only within the last 20 to 30 yr that potential candidates for these bioactive factors have been examined at a molecular level. Several, including parathyroid hormone-related protein, growth factors (transforming growth factor, insulin-like growth factor, epidermal growth factor), and serotonin, are synthesized within and act upon the gland and possess dynamic receptor activity resulting in diverse effects on growth, calcium homeostasis, and milk composition. This review will focus on the

  11. The role of orbital ultrasonography in distinguishing papilledema from pseudopapilledema

    PubMed Central

    Carter, S B; Pistilli, M; Livingston, K G; Gold, D R; Volpe, N J; Shindler, K S; Liu, G T; Tamhankar, M A

    2014-01-01

    Purpose To determine the sensitivity and specificity of orbital ultrasonography in distinguishing papilledema from pseudopapilledema in adult patients. Methods The records of all adult patients referred to the neuro-ophthalmology service who underwent orbital ultrasonography for the evaluation of suspected papilledema were reviewed. The details of history, ophthalmologic examination, and results of ancillary testing including orbital ultrasonography, MRI, and lumbar puncture were recorded. Results of orbital ultrasonography were correlated with the final diagnosis of papilledema or pseudopapilledema on the basis of the clinical impression of the neuro-ophthalmologist. Ultrasound was considered positive when the optic nerve sheath diameter was ≥3.3 mm along with a positive 30° test. Results The sensitivity of orbital ultrasonography for detection of papilledema was 90% (CI: 80.2–99.3%) and the specificity in detecting pseudopapilledema was 79% (CI: 67.7–90.7%). Conclusions Orbital ultrasonography is a rapid and noninvasive test that is highly sensitive, but less specific in differentiating papilledema from pseudopapilledema in adult patients, and can be useful in guiding further management of patients in whom the diagnosis is initially uncertain. PMID:25190532

  12. Prevention of mammary carcinogenesis by short-term estrogen and progestin treatments

    PubMed Central

    Rajkumar, Lakshmanaswamy; Guzman, Raphael C; Yang, Jason; Thordarson, Gudmundur; Talamantes, Frank; Nandi, Satyabrata

    2004-01-01

    Introduction Women who have undergone a full-term pregnancy before the age of 20 have one-half the risk of developing breast cancer compared with women who have never gone through a full-term pregnancy. This protective effect is observed universally among women of all ethnic groups. Parity in rats and mice also protects them against chemically induced mammary carcinogenesis. Methods Seven-week-old virgin Lewis rats were given N-methyl-N-nitrosourea. Two weeks later the rats were treated with natural or synthetic estrogens and progestins for 7–21 days by subcutaneous implantation of silastic capsules. Results In our current experiment, we demonstrate that short-term sustained exposure to natural or synthetic estrogens along with progestins is effective in preventing mammary carcinogenesis in rats. Treatment with 30 mg estriol plus 30 mg progesterone for 3 weeks significantly reduced the incidence of mammary cancer. Short-term exposure to ethynyl estradiol plus megesterol acetate or norethindrone was effective in decreasing the incidence of mammary cancers. Tamoxifen plus progesterone treatment for 3 weeks was able to confer only a transient protection from mammary carcinogenesis, while 2-methoxy estradiol plus progesterone was effective in conferring protection against mammary cancers. Conclusions The data obtained in the present study demonstrate that, in nulliparous rats, long-term protection against mammary carcinogenesis can be achieved by short-term treatments with natural or synthetic estrogen and progesterone combinations. PMID:14680498

  13. DNMT1 is essential for mammary and cancer stem cell maintenance and tumorigenesis

    PubMed Central

    Pathania, Rajneesh; Ramachandran, Sabarish; Elangovan, Selvakumar; Padia, Ravi; Yang, Pengyi; Cinghu, Senthilkumar; Veeranan-Karmegam, Rajalakshmi; Arjunan, Pachiappan; Gnana-Prakasam, Jaya P.; Fulzele, Sadanand; Pei, Lirong; Chang, Chang-Sheng; Choi, Hyeon; Shi, Huidong; Manicassamy, Santhakumar; Prasad, Puttur D.; Sharma, Suash; Ganapathy, Vadivel; Jothi, Raja; Thangaraju, Muthusamy

    2015-01-01

    Mammary stem/progenitor cells (MaSCs) maintain self-renewal of the mammary epithelium during puberty and pregnancy. DNA methylation provides a potential epigenetic mechanism for maintaining cellular memory during self-renewal. Although DNA methyltransferases (DNMTs) are dispensable for embryonic stem cell maintenance, their role in maintaining MaSCs and cancer stem cells (CSCs) in constantly replenishing mammary epithelium is unclear. Here we show that DNMT1 is indispensable for MaSC maintenance. Furthermore, we find that DNMT1 expression is elevated in mammary tumors, and mammary gland-specific DNMT1 deletion protects mice from mammary tumorigenesis by limiting the CSC pool. Through genome-scale methylation studies, we identify ISL1 as a direct DNMT1 target, hypermethylated and downregulated in mammary tumors and CSCs. DNMT inhibition or ISL1 expression in breast cancer cells limits CSC population. Altogether, our studies uncover an essential role for DNMT1 in MaSC and CSC maintenance and identify DNMT1-ISL1 axis as a potential therapeutic target for breast cancer treatment. PMID:25908435

  14. DNMT1 is essential for mammary and cancer stem cell maintenance and tumorigenesis.

    PubMed

    Pathania, Rajneesh; Ramachandran, Sabarish; Elangovan, Selvakumar; Padia, Ravi; Yang, Pengyi; Cinghu, Senthilkumar; Veeranan-Karmegam, Rajalakshmi; Arjunan, Pachiappan; Gnana-Prakasam, Jaya P; Sadanand, Fulzele; Pei, Lirong; Chang, Chang-Sheng; Choi, Jeong-Hyeon; Shi, Huidong; Manicassamy, Santhakumar; Prasad, Puttur D; Sharma, Suash; Ganapathy, Vadivel; Jothi, Raja; Thangaraju, Muthusamy

    2015-04-24

    Mammary stem/progenitor cells (MaSCs) maintain self-renewal of the mammary epithelium during puberty and pregnancy. DNA methylation provides a potential epigenetic mechanism for maintaining cellular memory during self-renewal. Although DNA methyltransferases (DNMTs) are dispensable for embryonic stem cell maintenance, their role in maintaining MaSCs and cancer stem cells (CSCs) in constantly replenishing mammary epithelium is unclear. Here we show that DNMT1 is indispensable for MaSC maintenance. Furthermore, we find that DNMT1 expression is elevated in mammary tumours, and mammary gland-specific DNMT1 deletion protects mice from mammary tumorigenesis by limiting the CSC pool. Through genome-scale methylation studies, we identify ISL1 as a direct DNMT1 target, hypermethylated and downregulated in mammary tumours and CSCs. DNMT inhibition or ISL1 expression in breast cancer cells limits CSC population. Altogether, our studies uncover an essential role for DNMT1 in MaSC and CSC maintenance and identify DNMT1-ISL1 axis as a potential therapeutic target for breast cancer treatment.

  15. Embryonic mammary signature subsets are activated in Brca1-/- and basal-like breast cancers

    PubMed Central

    2013-01-01

    Introduction Cancer is often suggested to result from development gone awry. Links between normal embryonic development and cancer biology have been postulated, but no defined genetic basis has been established. We recently published the first transcriptomic analysis of embryonic mammary cell populations. Embryonic mammary epithelial cells are an immature progenitor cell population, lacking differentiation markers, which is reflected in their very distinct genetic profiles when compared with those of their postnatal descendents. Methods We defined an embryonic mammary epithelial signature that incorporates the most highly expressed genes from embryonic mammary epithelium when compared with the postnatal mammary epithelial cells. We looked for activation of the embryonic mammary epithelial signature in mouse mammary tumors that formed in mice in which Brca1 had been conditionally deleted from the mammary epithelium and in human breast cancers to determine whether any genetic links exist between embryonic mammary cells and breast cancers. Results Small subsets of the embryonic mammary epithelial signature were consistently activated in mouse Brca1-/- tumors and human basal-like breast cancers, which encoded predominantly transcriptional regulators, cell-cycle, and actin cytoskeleton components. Other embryonic gene subsets were found activated in non-basal-like tumor subtypes and repressed in basal-like tumors, including regulators of neuronal differentiation, transcription, and cell biosynthesis. Several embryonic genes showed significant upregulation in estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and/or grade 3 breast cancers. Among them, the transcription factor, SOX11, a progenitor cell and lineage regulator of nonmammary cell types, is found highly expressed in some Brca1-/- mammary tumors. By using RNA interference to silence SOX11 expression in breast cancer cells, we found evidence that SOX11 regulates breast cancer cell

  16. Mammary artery harvesting using the Da Vinci Si robotic system

    PubMed Central

    Canale, Leonardo Secchin; Bonatti, Johannes

    2014-01-01

    Internal mammary artery harvesting is an essential part of any coronary artery bypass operation. Totally endoscopic coronary artery bypass graft surgery has become reality in many centers as a safe and effective alternative to conventional surgery in selected patients. Internal mammary artery harvesting is the initial part of the procedure and should be performed equally safely if one wants to achieve excellence in patency rates for the bypass. We here describe the technique for mammary harvesting with the Da Vinci Si robotic system. PMID:24896171

  17. Amphiregulin mediates self-renewal in an immortal mammary epithelial cell line with stem cell characteristics

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Booth, Brian W., E-mail: brbooth@clemson.edu; Institute for Biological Interfaces of Engineering, Clemson University, Clemson, SC 29634; Boulanger, Corinne A.

    2010-02-01

    Amphiregulin (AREG), a ligand for epidermal growth factor receptor, is required for mammary gland ductal morphogenesis and mediates estrogen actions in vivo, emerging as an essential growth factor during mammary gland growth and differentiation. The COMMA-D {beta}-geo (CD{beta}geo) mouse mammary cell line displays characteristics of normal mammary progenitor cells including the ability to regenerate a mammary gland when transplanted into the cleared fat pad of a juvenile mouse, nuclear label retention, and the capacity to form anchorage-independent mammospheres. We demonstrate that AREG is essential for formation of floating mammospheres by CD{beta}geo cells and that the mitogen activated protein kinase signalingmore » pathway is involved in AREG-mediated mammosphere formation. Addition of exogenous AREG promotes mammosphere formation in cells where AREG expression is knocked down by siRNA and mammosphere formation by AREG{sup -/-} mammary epithelial cells. AREG knockdown inhibits mammosphere formation by duct-limited mammary progenitor cells but not lobule-limited mammary progenitor cells. These data demonstrate AREG mediates the function of a subset of mammary progenitor cells in vitro.« less

  18. Amphiregulin mediates self-renewal in an immortal mammary epithelial cell line with stem cell characteristics.

    PubMed

    Booth, Brian W; Boulanger, Corinne A; Anderson, Lisa H; Jimenez-Rojo, Lucia; Brisken, Cathrin; Smith, Gilbert H

    2010-02-01

    Amphiregulin (AREG), a ligand for epidermal growth factor receptor, is required for mammary gland ductal morphogenesis and mediates estrogen actions in vivo, emerging as an essential growth factor during mammary gland growth and differentiation. The COMMA-D beta-geo (CDbetageo) mouse mammary cell line displays characteristics of normal mammary progenitor cells including the ability to regenerate a mammary gland when transplanted into the cleared fat pad of a juvenile mouse, nuclear label retention, and the capacity to form anchorage-independent mammospheres. We demonstrate that AREG is essential for formation of floating mammospheres by CDbetageo cells and that the mitogen activated protein kinase signaling pathway is involved in AREG-mediated mammosphere formation. Addition of exogenous AREG promotes mammosphere formation in cells where AREG expression is knocked down by siRNA and mammosphere formation by AREG(-/-) mammary epithelial cells. AREG knockdown inhibits mammosphere formation by duct-limited mammary progenitor cells but not lobule-limited mammary progenitor cells. These data demonstrate AREG mediates the function of a subset of mammary progenitor cells in vitro. Copyright 2009 Elsevier Inc. All rights reserved.

  19. Stromal matrix metalloproteinase-11 is involved in the mammary gland postnatal development.

    PubMed

    Tan, J; Buache, E; Alpy, F; Daguenet, E; Tomasetto, C-L; Ren, G-S; Rio, M-C

    2014-07-31

    MMP-11 is a bad prognosis paracrine factor in invasive breast cancers. However, its mammary physiological function remains largely unknown. In the present study we have investigated MMP-11 function during postnatal mammary gland development and function using MMP-11-deficient (MMP-11-/-) mice. Histological and immunohistochemical analyses as well as whole-mount mammary gland staining show alteration of the mammary gland in the absence of MMP-11, where ductal tree, alveolar structures and milk production are reduced. Moreover, a series of transplantation experiments allowed us to demonstrate that MMP-11 exerts an essential local paracrine function that favors mammary gland branching and epithelial cell outgrowth and invasion through adjacent connective tissues. Indeed, MMP-11-/- cleared fat pads are not permissive for wild-type epithelium development, whereas MMP-11-/- epithelium transplants grow normally when implanted in wild-type cleared fat pads. In addition, using primary mammary epithelial organoids, we show in vitro that this MMP-11 pro-branching effect is not direct, suggesting that MMP-11 acts via production/release of stroma-associated soluble factor(s). Finally, the lack of MMP-11 leads to decreased periductal collagen content, suggesting that MMP-11 has a role in collagen homeostasis. Thus, local stromal MMP-11 might also regulate mammary epithelial cell behavior mechanically by promoting extracellular matrix stiffness. Collectively, the present data indicate that MMP-11 is a paracrine factor involved during postnatal mammary gland morphogenesis, and support the concept that the stroma strongly impact epithelial cell behavior. Interestingly, stromal MMP-11 has previously been reported to favor malignant epithelial cell survival and promote cancer aggressiveness. Thus, MMP-11 has a paracrine function during mammary gland development that might be harnessed to promote tumor progression, exposing a new link between development and malignancy.

  20. Effect of Ultrasonography on Student Learning of Shoulder Anatomy and Landmarks.

    PubMed

    de Vries, Kristen D; Brown, Rebecca; Mazzie, Joseph; Jung, Min-Kyung; Yao, Sheldon C; Terzella, Michael J

    2018-01-01

    Ultrasonography is becoming more common in clinical use, and it has been shown to have promising results when introduced into medical school curricula. To determine whether the use of ultrasonography as an educational supplement can improve osteopathic medical students' confidence and ability to locate 4 specific shoulder anatomical landmarks: the coracoid process, the transverse process of T1, the long head of the biceps within the bicipital groove, and the supraspinatus tendon. In this randomized controlled study, first-year osteopathic medical students aged 18 years or older were recruited and randomly assigned to a group with exposure (ultrasonography group) or without exposure (control group) to an ultrasonography machine. First, a survey was administered to measure students' baseline knowledge of shoulder anatomy, confidence in palpation skills, and opinion on anatomical landmark identification teaching methods. Next, students were shown presentations on shoulder anatomy and allowed to practice locating and palpating the specified landmarks. Students in the ultrasonography group were also given instruction on the use of ultrasonography. All students were asked to locate each of the 4 specified anatomical landmarks and then given a follow-up survey. A Mann Whitney U test was used to compare the confidence of the students before and after the intervention. A secondary analysis was performed to compare the degree of deviance from the correct position of the specified anatomical landmark between the ultrasonography and control groups. P values less than .05 were considered statistically significant. Sixty-four students participated. Compared with the control group, students in the ultrasonography group had a greater increase in confidence after the session in their ability to locate the coracoid process, bicipital tendon, and supraspinatus tendon (P=.022, P=.029, P=.44, respectively). Students in the ultrasonography group were also able to more accurately palpate

  1. Serum acute phase protein concentrations in female dogs with mammary tumors.

    PubMed

    Tecles, Fernando; Caldín, Marco; Zanella, Anna; Membiela, Francisco; Tvarijonaviciute, Asta; Subiela, Silvia Martínez; Cerón, José Joaquín

    2009-03-01

    Acute phase proteins (APPs) are proteins whose concentrations in serum change after any inflammatory stimulus or tissue damage. The aim of the current study was to evaluate 3 positive APPs (C-reactive protein, serum amyloid A, and haptoglobin) and 1 negative APP (albumin) in female dogs with mammary neoplasia. Acute phase proteins were studied in 70 female dogs aged 8-12 years in the following groups: healthy (n = 10); mammary tumors in stages I (n = 19), II (n = 5), III (n = 6), IV (n = 5), and V (n = 7); and with mammary neoplasia plus a concomitant disease (n = 18). In animals with mammary neoplasia, significant increases of positive APPs were only detected in those that had metastasis or a neoplasm with a diameter greater than 5 cm and ulceration. Dogs with mammary neoplasia and a concomitant disease also had high C-reactive protein concentrations. Albumin concentration was decreased in animals with metastasis and with a concomitant disease. The results of the present study indicate that the acute phase response could be stimulated in female dogs with mammary gland tumors because of different factors, such as metastasis, large size of the primary mass, and ulceration or secondary inflammation of the neoplasm.

  2. [Diagnostic utility of endoscopic ultrasonography elastography and contrast-enhanced harmonic endoscopic ultrasonography in a patient with type 2 autoimmune pancreatitis].

    PubMed

    Yokode, Masataka; Shiomi, Hideyuki; Itai, Ryosuke; Mikami, Sakae; Yamashita, Yukimasa; Nakano, Ryota; Ezaki, Takeshi; Masuda, Atsuhiro; Zen, Yoh

    2018-01-01

    A referring hospital diagnosed a 57-year-old man with a pancreatic head mass. The initial endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) was inconclusive because of the small sample size. Endoscopic ultrasonography elastography (EUS-EG) and contrast-enhanced harmonic endoscopic ultrasonography (CE-EUS), conducted at our institute, raised the possibility of mass-forming pancreatitis or autoimmune pancreatitis (AIP). A repeat EUS-FNA revealed inflammatory changes, including a neutrophilic duct injury suggestive of type 2 AIP. The pancreatic lesion responded well to the steroid therapy. The present case suggests that EUS-EG and CE-EUS may be useful for diagnostic exclusion of pancreatic cancers, and the combined use of EUS-EG and CE-EUS, with EUS-FNA, may help characterize inflammatory pancreatic lesions.

  3. Cardiovascular ultrasonography detection of embolic sources in trauma.

    PubMed

    Saranteas, Theodosios; Mavrogenis, Andreas F; Poularas, John; Kostroglou, Andreas; Mandila, Christina; Panou, Fotios

    2018-06-01

    Venous thromboembolism (deep vein thrombosis and pulmonary embolism) and bone cement implantation syndrome are major sources of embolic events in trauma patients. In these patients, embolic events due to venous thromboembolism and bone cement implantation syndrome have been detected with cardiac and vascular ultrasonography in the emergency setting, during the perioperative period, and in the intensive care unit. This article discusses the ultrasonography modalities and imaging findings of embolic events related to venous thromboembolism and bone cement implantation syndrome. The aim is to present a short review with exceptional illustrations that can enable physicians to identify sources of emboli in trauma patients with cardiovascular ultrasonography. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Th-POK regulates mammary gland lactation through mTOR-SREBP pathway.

    PubMed

    Zhang, Rui; Ma, Huimin; Gao, Yuan; Wu, Yanjun; Qiao, Yuemei; Geng, Ajun; Cai, Cheguo; Han, Yingying; Zeng, Yi Arial; Liu, Xiaolong; Ge, Gaoxiang

    2018-02-01

    The Th-inducing POK (Th-POK, also known as ZBTB7B or cKrox) transcription factor is a key regulator of lineage commitment of immature T cell precursors. It is yet unclear the physiological functions of Th-POK besides helper T cell differentiation. Here we show that Th-POK is restrictedly expressed in the luminal epithelial cells in the mammary glands that is upregulated at late pregnancy and lactation. Lineage restrictedly expressed Th-POK exerts distinct biological functions in the mammary epithelial cells and T cells in a tissue-specific manner. Th-POK is not required for mammary epithelial cell fate determination. Mammary gland morphogenesis in puberty and alveologenesis in pregnancy are phenotypically normal in the Th-POK-deficient mice. However, Th-POK-deficient mice are defective in triggering the onset of lactation upon parturition with large cellular lipid droplets retained within alveolar epithelial cells. As a result, Th-POK knockout mice are unable to efficiently secret milk lipid and to nurse the offspring. Such defect is mainly attributed to the malfunctioned mammary epithelial cells, but not the tissue microenvironment in the Th-POK deficient mice. Th-POK directly regulates expression of insulin receptor substrate-1 (IRS-1) and insulin-induced Akt-mTOR-SREBP signaling. Th-POK deficiency compromises IRS-1 expression and Akt-mTOR-SREBP signaling in the lactating mammary glands. Conversely, insulin induces Th-POK expression. Thus, Th-POK functions as an important feed-forward regulator of insulin signaling in mammary gland lactation.

  5. Th-POK regulates mammary gland lactation through mTOR-SREBP pathway

    PubMed Central

    Wu, Yanjun; Qiao, Yuemei; Geng, Ajun; Cai, Cheguo; Han, Yingying; Zeng, Yi Arial

    2018-01-01

    The Th-inducing POK (Th-POK, also known as ZBTB7B or cKrox) transcription factor is a key regulator of lineage commitment of immature T cell precursors. It is yet unclear the physiological functions of Th-POK besides helper T cell differentiation. Here we show that Th-POK is restrictedly expressed in the luminal epithelial cells in the mammary glands that is upregulated at late pregnancy and lactation. Lineage restrictedly expressed Th-POK exerts distinct biological functions in the mammary epithelial cells and T cells in a tissue-specific manner. Th-POK is not required for mammary epithelial cell fate determination. Mammary gland morphogenesis in puberty and alveologenesis in pregnancy are phenotypically normal in the Th-POK-deficient mice. However, Th-POK-deficient mice are defective in triggering the onset of lactation upon parturition with large cellular lipid droplets retained within alveolar epithelial cells. As a result, Th-POK knockout mice are unable to efficiently secret milk lipid and to nurse the offspring. Such defect is mainly attributed to the malfunctioned mammary epithelial cells, but not the tissue microenvironment in the Th-POK deficient mice. Th-POK directly regulates expression of insulin receptor substrate-1 (IRS-1) and insulin-induced Akt-mTOR-SREBP signaling. Th-POK deficiency compromises IRS-1 expression and Akt-mTOR-SREBP signaling in the lactating mammary glands. Conversely, insulin induces Th-POK expression. Thus, Th-POK functions as an important feed-forward regulator of insulin signaling in mammary gland lactation. PMID:29420538

  6. Short-term exposure to pregnancy levels of estrogen prevents mammary carcinogenesis

    PubMed Central

    Rajkumar, Lakshmanaswamy; Guzman, Raphael C.; Yang, Jason; Thordarson, Gudmundur; Talamantes, Frank; Nandi, Satyabrata

    2001-01-01

    It is well established that pregnancy early in life reduces the risk of breast cancer in women and that this effect is universal. This phenomenon of parity protection against mammary cancer is also observed in rodents. Earlier studies have demonstrated that short-term administration of estradiol (E) in combination with progesterone mimics the protective effect of parity in rats. In this study, the lowest effective E dosage for preventing mammary cancer was determined. Rats were injected with N-methyl-N-nitrosourea at 7 weeks of age; 2 weeks later, the rats were subjected to sustained treatment with 20 μg, 100 μg, 200 μg, or 30 mg of E in silastic capsules for 3 weeks. Treatments with 100 μg, 200 μg, and 30 mg of E resulted in serum levels of E equivalent to those of pregnancy and were highly effective in preventing mammary cancer. E treatment (20 μg) did not result in pregnancy levels of E and was not effective in reducing the mammary cancer incidence. In another set of experiments, we determined the effect of different durations of E with or without progesterone treatments on mammary carcinogenesis. These experiments indicate that a period as short as one-third the period of gestation is sufficient to induce protection against mammary carcinogenesis. The pioneering aspect of our study in contrast to long-term estrogen exposure, which is thought to increase the risk of breast cancer, is that short-term sustained treatments with pregnancy levels of E can induce protection against frank mammary cancer. PMID:11573010

  7. [A Multimedia Tutorial to Train Ultrasonography of the Thyroid for Medical Students].

    PubMed

    Ritter, Julia; Wolfram, Maximilian; Schuler, Stefan; Guntinas-Lichius, Orlando

    2017-11-01

    Physicians in education often have poor experience in practice and assessment of ultrasonography on entering their profession, due to a deficiency of training offers during their study of medicine. Hence, a multimedia device for stepwise learning and training ultrasonography of the thyroid was developed. A software for a portable ultrasonography system was used to design a multimedia device for ultrasonography of the thyroid. It allows the user to illustrate texts and pictorial material simultaneously with ultrasound examination in order to compare own findings with examples from a database. The device was evaluated by 8 medical students and compared to a tutor-guided training. A structured, stepwise manual for ultrasonography of the thyroid with a large content of examples in different sectional images was designed for simultaneous reconstruction with the ultrasonography device. The informative content of the device and the replicability of the examination procedure were evaluated positively. Assessment respecting clarity, eligibility for users without experience and learning success was varying. The tutorial to learn and train ultrasonography of the thyroid is an instrument for self-learning and improving practical education in ultrasonography in medical education. In the next version, the manual for the examination will be structured in greater detail. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Immortalized bovine mammary epithelial cells express stem cell markers and differentiate in vitro.

    PubMed

    Hu, Han; Zheng, Nan; Gao, Haina; Dai, Wenting; Zhang, Yangdong; Li, Songli; Wang, Jiaqi

    2016-08-01

    The bovine mammary epithelial cell is a secretory cell, and its cell number and secretory activity determine milk production. In this study, we immortalized a bovine mammary epithelial cell line by SV40 large T antigen gene using a retrovirus based on Chinese Holstein primary mammary epithelial cells (CMEC) cultured in vitro. An immortalized bovine mammary epithelial cell line surpassed the 50-passage mark and was designated the CMEC-H. The immortalized mammary epithelial cells grew in close contact with each other and exhibited the typical cobblestone morphology characteristic with obvious boundaries. The telomerase expression of CMEC-H has consistently demonstrated the presence of telomerase activity as an immortalized cell line, but the cell line never induced tumor formation in nude mice. CMEC-H expressed epithelial (cytokeratins CK7, CK8, CK18, and CK19), mesenchymal (vimentin), and stem/progenitor (CD44 and p63) cell markers. The induced expression of milk proteins, αS1 -casein, β-casein, κ-casein, and butyrophilin, indicated that CMEC-H maintained the synthesis function of the mammary epithelial cells. The established immortalized bovine mammary epithelial cell line CMEC-H is capable of self-renewal and differentiation and can serve as a valuable reagent for studying the physiological mechanism of the mammary gland. © 2016 International Federation for Cell Biology.

  9. The RhoGEF Net1 Is Required for Normal Mammary Gland Development

    PubMed Central

    Zuo, Yan; Berdeaux, Rebecca

    2014-01-01

    Neuroepithelial transforming gene 1 (Net1) is a RhoA subfamily-specific guanine nucleotide exchange factor that is overexpressed in human breast cancer and is required for breast cancer cell migration and invasion. However, the role of Net1 in normal mammary gland development or function has never been assessed. To understand the role of Net1 in the mammary gland, we have created a conditional Net1 knockout mouse model. Whole-body deletion of Net1 results in delayed mammary gland development during puberty characterized by slowed of ductal extension and reduced ductal branching. Epithelial cells within the developing ducts show reduced proliferation that is accompanied by diminished estrogen receptor-α expression and activity. Net1-deficient mammary glands also exhibit reduced phosphorylation of regulatory subunits of myosin light chain and myosin light-chain phosphatase, indicating that RhoA-dependent actomyosin contraction is compromised. Net1 deficiency also leads to disorganization of myoepithelial and ductal epithelial cells and increased periductal collagen deposition. Mammary epithelial cell transplantation experiments indicate that reduced ductal branching and disorganization are cell autonomous. These data identify for the first time a role for NET1 in vivo and indicate that NET1 expression is essential for the proliferation and differentiation of mammary epithelial cells in the developing mammary gland. PMID:25321414

  10. Progesterone facilitates chromosome instability (aneuploidy) in p53 null normal mammary epithelial cells

    NASA Technical Reports Server (NTRS)

    Goepfert, T. M.; McCarthy, M.; Kittrell, F. S.; Stephens, C.; Ullrich, R. L.; Brinkley, B. R.; Medina, D.

    2000-01-01

    Mammary epithelial cells from p53 null mice have been shown recently to exhibit an increased risk for tumor development. Hormonal stimulation markedly increased tumor development in p53 null mammary cells. Here we demonstrate that mammary tumors arising in p53 null mammary cells are highly aneuploid, with greater than 70% of the tumor cells containing altered chromosome number and a mean chromosome number of 56. Normal mammary cells of p53 null genotype and aged less than 14 wk do not exhibit aneuploidy in primary cell culture. Significantly, the hormone progesterone, but not estrogen, increases the incidence of aneuploidy in morphologically normal p53 null mammary epithelial cells. Such cells exhibited 40% aneuploidy and a mean chromosome number of 54. The increase in aneuploidy measured in p53 null tumor cells or hormonally stimulated normal p53 null cells was not accompanied by centrosome amplification. These results suggest that normal levels of progesterone can facilitate chromosomal instability in the absence of the tumor suppressor gene, p53. The results support the emerging hypothesis based both on human epidemiological and animal model studies that progesterone markedly enhances mammary tumorigenesis.

  11. Mammary gigantism and D-penicillamine.

    PubMed

    Finer, N; Emery, P; Hicks, B H

    1984-09-01

    Mammary gigantism is a rare complication of D-penicillamine treatment. We report a further case with pathological and endocrine details together with a review of the seven cases previously reported and possible mechanisms.

  12. Investigating the Role of FIP200 in Mammary Carcinogenesis Using a Transgenic Mouse Model

    DTIC Science & Technology

    2006-04-01

    I analyzed virgin and lactating female mice in which FAK is specifically deleted in the mammary epithelium. No morphological abnormalities were found...in the mammary gland of virgin mice however, lactating mice have severe lobulo-alveolar hypoplasia in the mammary gland. 15. SUBJECT TERMS... virgin and lactating female mice in which FAK is specifically deleted in the mammary epithelium. No morphological abnormalities were found in the

  13. Brca1 regulates in vitro differentiation of mammary epithelial cells.

    PubMed

    Kubista, Marion; Rosner, Margit; Kubista, Ernst; Bernaschek, Gerhard; Hengstschläger, Markus

    2002-07-18

    Murine Brca1 is widely expressed during development in different tissues. Why alterations of BRCA1 lead specifically to breast and ovarian cancer is currently not clarified. Here we show that Brca1 protein expression is upregulated during mammary epithelial differentiation of HC11 cells, during differentiation of C2C12 myoblasts into myotubes and during neuronal differentiation of N1E-115 cells. Ectopic overexpression of BRCA1 and downregulation of endogenous Brca1 expression specifically affect the regulation of mammary epithelial cell differentiation. Accelerated mammary epithelial cell differentiation upon high ectopic BRCA1 expression is not a consequence of the anti-proliferative capacity of this tumor suppressor and independent of functional p53. Overexpression of the BRCA1 variant lacking the large central exon 11 has no effects on mammary epithelial cell differentiation. These data provide new insights into the cellular role of Brca1.

  14. The mammary gland in domestic ruminants: a systems biology perspective.

    PubMed

    Ferreira, Ana M; Bislev, Stine L; Bendixen, Emøke; Almeida, André M

    2013-12-06

    Milk and dairy products are central elements in the human diet. It is estimated that 108kg of milk per year are consumed per person worldwide. Therefore, dairy production represents a relevant fraction of the economies of many countries, being cattle, sheep, goat, water buffalo, and other ruminants the main species used worldwide. An adequate management of dairy farming cannot be achieved without the knowledge on the biological mechanisms behind lactation in ruminants. Thus, understanding the morphology, development and regulation of the mammary gland in health, disease and production is crucial. Presently, innovative and high-throughput technologies such as genomics, transcriptomics, proteomics and metabolomics allow a much broader and detailed knowledge on such issues. Additionally, the application of a systems biology approach to animal science is vastly growing, as new advances in one field of specialization or animal species lead to new lines of research in other areas or/and are expanded to other species. This article addresses how modern research approaches may help us understand long-known issues in mammary development, lactation biology and dairy production. Dairy production depends upon the knowledge of the morphology and regulation of the mammary gland and lactation. High-throughput technologies allow a much broader and detailed knowledge on the biology of the mammary gland. This paper reviews the major contributions that genomics, transcriptomics, metabolomics and proteomics approaches have provided to understand the regulation of the mammary gland in health, disease and production. In the context of mammary gland "omics"-based research, the integration of results using a Systems Biology Approach is of key importance. © 2013.

  15. Ultrasonography of the hand, wrist, and elbow.

    PubMed

    Bodor, Marko; Fullerton, Brad

    2010-08-01

    High-frequency diagnostic ultrasonography of the hand, wrist and elbow has significant potential to improve the quality of diagnosis and care provided by neuromuscular and musculoskeletal specialists. In patients referred for weakness, pain and numbness of the hand, wrist or elbow, diagnostic ultrasonography can be an adjunct to electrodiagnosis and help in identifying ruptured tendons and treating conditions such as carpal tunnel syndrome or trigger finger. Use of a small high-frequency (>10-15 MHz) transducer, an instrument with a blunt pointed tip to enhance sonopalpation and a model of the hand, wrist and elbow is advised to enhance visualization of small anatomical structures and complex bony contours. A range of conditions, including tendon and ligament ruptures, trigger finger, de Quervain tenosynovitis, intersection syndrome, lateral epicondylitis, and osteoarthritis, is described along with detailed ultrasonography-guided injection techniques for carpal tunnel syndrome and trigger finger. Copyright 2010 Elsevier Inc. All rights reserved.

  16. Phenotypic conversion of human mammary carcinoma cells by autocrine human growth hormone

    PubMed Central

    Mukhina, Svetlana; Mertani, Hichem C.; Guo, Ke; Lee, Kok-Onn; Gluckman, Peter D.; Lobie, Peter E.

    2004-01-01

    We report here that autocrine production of human growth hormone (hGH) results in a phenotypic conversion of mammary carcinoma cells such that they exhibit the morphological and molecular characteristics of a mesenchymal cell, including expression of fibronectin and vimentin. Autocrine production of hGH resulted in reduced plakoglobin expression and relocalization of E-cadherin to the cytoplasm, leading to dissolution of cell-cell contacts and decreased cell height. These phenotypic changes were accompanied by an increase in cell motility, elevated activity of specific matrix metalloproteinases, and an acquired ability to invade a reconstituted basement membrane. Forced expression of plakoglobin significantly decreased mammary carcinoma cell migration and invasion stimulated by autocrine hGH. In vivo, autocrine hGH stimulated local invasion of mammary carcinoma cells concomitant with a prominent stromal reaction in comparison with well delineated and capsulated growth of mammary carcinoma cells lacking autocrine production of hGH. Thus, autocrine production of hGH by mammary carcinoma cells is sufficient for generation of an invasive phenotype. Therapeutic targeting of autocrine hGH may provide a mechanistic approach to prevent metastatic extension of human mammary carcinoma. PMID:15353581

  17. The Role of DN-GSK3beta in Mammary Tumorigenesis

    DTIC Science & Technology

    2006-07-01

    factors and dramatically increases their transcriptional activity. Genes up- regulated by TCF/LEF include embryologic genes, such as siamois and engrailed...and increased apoptosis occurs in the mammary epithelia (33). Overexpression of the regulator CK2a also promotes mammary tumorigenesis (34). In this

  18. Familial intra-areolar polythelia with mammary hypoplasia.

    PubMed

    Rintala, A; Norio, R

    1982-01-01

    Dysplastic divided nipples (intra-areolar polythelia) have been found bilaterally in a mother, her two daughters and one son. Two of the patients had mammary hypoplasia, one had unilateral hypoplasia of the pectoral muscle and duplication of the renal pelvis and ureter. The mammary findings are consistent with autosomal dominant inheritance. Whether they represent a new mammo-renal syndrome is uncertain. Reconstructive surgery was performed on two patients. Due to the deformity the mother was unable to nurse her children; following reconstructive surgery the daughter was able to feed her baby normally.

  19. Over-expression of mammaglobin-B in canine mammary tumors.

    PubMed

    Pandey, Mamta; Sunil Kumar, B V; Gupta, Kuldip; Sethi, Ram Saran; Kumar, Ashwani; Verma, Ramneek

    2018-06-15

    Mammaglobin, a member of secretoglobin family has been recognized as a breast cancer associated protein. Though the exact function of the protein is not fully known, its expression has been reported to be upregulated in human breast cancer.We focused on studying the expression of mammaglobin-B gene and protein in canine mammary tumor (CMT) tissue. Expression of mammaglobin-B mRNA and protein were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC), respectively. High levels of mammaglobin-B mRNA expression (6.663 ± 0.841times) was observed in CMT as compared to age and breed matched healthy controls. Further, expression of mammaglobin-B protein was detected in paraffin-embedded mammary tumor tissues from the same subjects by IHC. Mammaglobin-B protein was overexpressed only in 6.67% of healthy mammary glands while, a high level of its expression was scored in 76.7% of the CMT subjects. Moreover, no significant differences in terms of IHC score and qRT-PCR score with respect to CMT histotypes or tumor grades were observed, indicating that mammaglobin-B over-expression occurred irrespective of CMT types or grades. Overall, significantly increased expression of mammaglobin-B protein was found in CMTs with respect to healthy mammary glands, which positively correlates to its transcript. These findings suggest that overexpression of mammaglobin-B is associated with tumors of canine mammary glands.

  20. Mammary fibroadenomatous hyperplasia in a young cat attributed to treatment with megestrol acetate.

    PubMed

    MacDougall, Lori D

    2003-03-01

    A male, neutered cat was presented for lethargy, reluctance to walk, and mammary enlargement after recent treatment with megestrol acetate. Mammary fibroadenomatous hyperplasia was diagnosed on the basis of history, clinical signs, and histopathological findings. Pathogenesis, clinical signs, and treatment options for mammary fibroadenomatous hyperplasia attributed to megestrol acetate treatment are discussed.

  1. Notch3 marks clonogenic mammary luminal progenitor cells in vivo.

    PubMed

    Lafkas, Daniel; Rodilla, Veronica; Huyghe, Mathilde; Mourao, Larissa; Kiaris, Hippokratis; Fre, Silvia

    2013-10-14

    The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive "triple negative" human breast cancer. However, the specific cells expressing this Notch paralogue in the mammary gland remain unknown. Using a conditionally inducible Notch3-CreERT2(SAT) transgenic mouse, we genetically marked Notch3-expressing cells throughout mammary gland development and followed their lineage in vivo. We demonstrate that Notch3 is expressed in a highly clonogenic and transiently quiescent luminal progenitor population that gives rise to a ductal lineage. These cells are capable of surviving multiple successive pregnancies, suggesting a capacity to self-renew. Our results also uncover a role for the Notch3 receptor in restricting the proliferation and consequent clonal expansion of these cells.

  2. Notch3 marks clonogenic mammary luminal progenitor cells in vivo

    PubMed Central

    Lafkas, Daniel; Rodilla, Veronica; Huyghe, Mathilde; Mourao, Larissa; Kiaris, Hippokratis

    2013-01-01

    The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive “triple negative” human breast cancer. However, the specific cells expressing this Notch paralogue in the mammary gland remain unknown. Using a conditionally inducible Notch3-CreERT2SAT transgenic mouse, we genetically marked Notch3-expressing cells throughout mammary gland development and followed their lineage in vivo. We demonstrate that Notch3 is expressed in a highly clonogenic and transiently quiescent luminal progenitor population that gives rise to a ductal lineage. These cells are capable of surviving multiple successive pregnancies, suggesting a capacity to self-renew. Our results also uncover a role for the Notch3 receptor in restricting the proliferation and consequent clonal expansion of these cells. PMID:24100291

  3. Relationship between histology, development and tumorigenesis of mammary gland in female rat

    PubMed Central

    LÍŠKA, Ján; BRTKO, Július; DUBOVICKÝ, Michal; MACEJOVÁ, Dana; KISSOVÁ, Viktória; POLÁK, Štefan; UJHÁZY, Eduard

    2015-01-01

    The mammary gland is a dynamic organ that undergoes structural and functional changes associated with growth, reproduction, and post-menopausal regression. The postnatal transformations of the epithelium and stromal cells of the mammary gland may contribute to its susceptibility to carcinogenesis. The increased cancer incidence in mammary glands of humans and similarly of rodents in association with their development is believed to be partly explained by proliferative activity together with lesser degree of differentiation, but it is not completely understood how the virgin gland retains its higher susceptibility to carcinogenesis. During its developmental cycle, the mammary gland displays many of the properties associated with breast cancer. An early first full-term pregnancy may have a protective effect. Rodent models are useful for investigating potential breast carcinogens. The purpose of this review is to help recognizing histological appearance of the epithelium and the stroma of the normal mammary gland in rats, and throughout its development in relation to tumorigenic potential. PMID:26424555

  4. [Analysis of eye ultrasonography in patients with trinitrotoluene cataract].

    PubMed

    Huang, Dongmei; Zhu, Linping; Yang, Jinping; Wu, Donping

    2015-04-01

    To evaluate the diagnostic value of ultrasonography for trinitrotoluene (TNT) cataract. The morphology and internal echoes of 90 lenses of 45 TNT cataract patients and 120 lenses of 60 healthy adults were observed and compared using ultrasonography and slit lamp, and the hemodynamic parameters of the post-ophthalmic artery were also measured. The findings of the slit-lamp microscope were regarded as diagnostic criteria, and the sensitivity, specificity, and accordance rate of ultrasonography in the diagnosis of TNT cataract were calculated. The sensitivity, specificity, and accordance rate of ultrasonography in the diagnosis of TNT cataract were 93.33%, 100.00%, and 97.14%, respectively; the positive and negative predictive values were 100% and 95.23%, respectively; the positive and negative likelihood ratios were 93.33 and 0.67, especuvey. With the progression TNT cataract, utrasonography showed that the lenses demonstrated morphological changes (spindle-shaped, spherical, and discoid morphologies), and the arc echoes of the posterior capsule were thickened and enhanced. The TNT cataract patients showed significantly lower peak systolic velocity and end-diastolic velocity of the ophthalmic artery (OA) and central retinal artery (P<0.01) and a significantly higher resistance index (P<0.05) than the healthy adults. The sensitivity of ultrasonography in the diagnosis of TNT cataract is similar to that of slit lamp. Ultrasonography can demonstrate objectively the shape, range, and degree of lens opacity in an efficient manner, which is conducive to the diagnosis and staging of TNT cataract by slit lamp, and can also provide hemodynamic information of the OA, thus providing new ideas for clinical physicians in evaluating the disease and clinical efficacy as well as exploring therapies.

  5. The Analysis of Cell Population Dynamics in Mammary Gland Development and Tumorigenesis

    DTIC Science & Technology

    2005-08-01

    AD Award Number: DAMD17-03-1-0498 TITLE: The Analysis of Cell Population Dynamics in Mammary Gland Development and Tumorigenesis PRINCIPAL...Summary 1 Aug 2004 - 31 Jul 2005 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER The Analysis of Cell Population Dynamics in Mammary Gland Development and...STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The mammary gland is made up of several epithelial cell

  6. From genes to milk: genomic organization and epigenetic regulation of the mammary transcriptome.

    PubMed

    Lemay, Danielle G; Pollard, Katherine S; Martin, William F; Freeman Zadrowski, Courtneay; Hernandez, Joseph; Korf, Ian; German, J Bruce; Rijnkels, Monique

    2013-01-01

    Even in genomes lacking operons, a gene's position in the genome influences its potential for expression. The mechanisms by which adjacent genes are co-expressed are still not completely understood. Using lactation and the mammary gland as a model system, we explore the hypothesis that chromatin state contributes to the co-regulation of gene neighborhoods. The mammary gland represents a unique evolutionary model, due to its recent appearance, in the context of vertebrate genomes. An understanding of how the mammary gland is regulated to produce milk is also of biomedical and agricultural importance for human lactation and dairying. Here, we integrate epigenomic and transcriptomic data to develop a comprehensive regulatory model. Neighborhoods of mammary-expressed genes were determined using expression data derived from pregnant and lactating mice and a neighborhood scoring tool, G-NEST. Regions of open and closed chromatin were identified by ChIP-Seq of histone modifications H3K36me3, H3K4me2, and H3K27me3 in the mouse mammary gland and liver tissue during lactation. We found that neighborhoods of genes in regions of uniquely active chromatin in the lactating mammary gland, compared with liver tissue, were extremely rare. Rather, genes in most neighborhoods were suppressed during lactation as reflected in their expression levels and their location in regions of silenced chromatin. Chromatin silencing was largely shared between the liver and mammary gland during lactation, and what distinguished the mammary gland was mainly a small tissue-specific repertoire of isolated, expressed genes. These findings suggest that an advantage of the neighborhood organization is in the collective repression of groups of genes via a shared mechanism of chromatin repression. Genes essential to the mammary gland's uniqueness are isolated from neighbors, and likely have less tolerance for variation in expression, properties they share with genes responsible for an organism's survival.

  7. ATM is required for SOD2 expression and homeostasis within the mammary gland.

    PubMed

    Dyer, Lisa M; Kepple, Jessica D; Ai, Lingbao; Kim, Wan-Ju; Stanton, Virginia L; Reinhard, Mary K; Backman, Lindsey R F; Streitfeld, W Scott; Babu, Nivetha Ramesh; Treiber, Nicolai; Scharffetter-Kochanek, Karin; McKinnon, Peter J; Brown, Kevin D

    2017-12-01

    ATM activates the NF-κB transcriptional complex in response to genotoxic and oxidative stress. The purpose of this study was to examine if the NF-κB target gene and critical antioxidant SOD2 (MnSOD) in cultured mammary epithelium is also ATM-dependent, and what phenotypes arise from deletion of ATM and SOD2 within the mammary gland. SOD2 expression was studied in human mammary epithelial cells and MCF10A using RNAi to knockdown ATM or the NF-κB subunit RelA. To study ATM and SOD2 function in mammary glands, mouse lines containing Atm or Sod2 genes containing LoxP sites were mated with mice harboring Cre recombinase under the control of the whey acidic protein promoter. Quantitative PCR was used to measure gene expression, and mammary gland structure was studied using histology. SOD2 expression is ATM- and RelA-dependent, ATM knockdown renders cells sensitive to pro-oxidant exposure, and SOD mimetics partially rescue this sensitivity. Mice with germline deletion of Atm fail to develop mature mammary glands, but using a conditional knockout approach, we determined that Atm deletion significantly diminished the expression of Sod2. We also observed that these mice (termed Atm Δ/Δ ) displayed a progressive lactation defect as judged by reduced pup growth rate, aberrant lobulo-alveolar structure, diminished milk protein gene expression, and increased apoptosis within lactating glands. This phenotype appears to be linked to dysregulated Sod2 expression as mammary gland-specific deletion of Sod2 phenocopies defects observed in Atm Δ/Δ dams. We conclude that ATM is required to promote expression of SOD2 within the mammary epithelium, and that both ATM and SOD2 play a crucial role in mammary gland homeostasis.

  8. Ultrasonography in diagnosing chronic pancreatitis: New aspects

    PubMed Central

    Dimcevski, Georg; Erchinger, Friedemann G; Havre, Roald; Gilja, Odd Helge

    2013-01-01

    The course and outcome is poor for most patients with pancreatic diseases. Advances in pancreatic imaging are important in the detection of pancreatic diseases at early stages. Ultrasonography as a diagnostic tool has made, virtually speaking a technical revolution in medical imaging in the new millennium. It has not only become the preferred method for first line imaging, but also, increasingly to clarify the interpretation of other imaging modalities to obtain efficient clinical decision. We review ultrasonography modalities, focusing on advanced pancreatic imaging and its potential to substantially improve diagnosis of pancreatic diseases at earlier stages. In the first section, we describe scanning techniques and examination protocols. Their consequences for image quality and the ability to obtain complete and detailed visualization of the pancreas are discussed. In the second section we outline ultrasonographic characteristics of pancreatic diseases with emphasis on chronic pancreatitis. Finally, new developments in ultrasonography of the pancreas such as contrast enhanced ultrasound and elastography are enlightened. PMID:24259955

  9. Mammary fibroadenomatous hyperplasia in a young cat attributed to treatment with megestrol acetate

    PubMed Central

    MacDougall, Lori D.

    2003-01-01

    A male, neutered cat was presented for lethargy, reluctance to walk, and mammary enlargement after recent treatment with megestrol acetate. Mammary fibroadenomatous hyperplasia was diagnosed on the basis of history, clinical signs, and histopathological findings. Pathogenesis, clinical signs, and treatment options for mammary fibroadenomatous hyperplasia attributed to megestrol acetate treatment are discussed. PMID:12677692

  10. Immersion ultrasonography: simultaneous A-scan and B-scan.

    PubMed

    Coleman, D J; Dallow, R L; Smith, M E

    1979-01-01

    In eyes with opaque media, ophthalmic ultrasound provides a unique source of information that can dramatically affect the course of patient management. In addition, when an ocular abnormality can be visualized, ultrasonography provides information that supplements and complements other diagnostic testing. It provides documentation and differentiation of abnormal states, such as vitreous hemorrhage and intraocular tumor, as well as differentiation of orbital tumors from inflammatory causes of exophthalmos. Additional capabilities of ultrasound are biometric determinations for calculation of intraocular lens implant powers and drug-effectiveness studies. Maximal information is derived from ultrasonography when A-scan and B-scan techniques are employed simultaneously. Flexibility of electronics, variable-frequency transducers, and the use of several different manual scanning patterns aid in detection and interpretation of results. The immersion system of ultrasonography provides these features optimally.

  11. Biological and genetic properties of the p53 null preneoplastic mammary epithelium

    NASA Technical Reports Server (NTRS)

    Medina, Daniel; Kittrell, Frances S.; Shepard, Anne; Stephens, L. Clifton; Jiang, Cheng; Lu, Junxuan; Allred, D. Craig; McCarthy, Maureen; Ullrich, Robert L.

    2002-01-01

    The absence of the tumor suppressor gene p53 confers an increased tumorigenic risk for mammary epithelial cells. In this report, we describe the biological and genetic properties of the p53 null preneoplastic mouse mammary epithelium in a p53 wild-type environment. Mammary epithelium from p53 null mice was transplanted serially into the cleared mammary fat pads of p53 wild-type BALB/c female to develop stable outgrowth lines. The outgrowth lines were transplanted for 10 generations. The outgrowths were ductal in morphology and progressed through ductal hyperplasia and ductal carcinoma in situ before invasive cancer. The preneoplastic outgrowth lines were immortal and exhibited activated telomerase activity. They are estrogen and progesterone receptor-positive, and aneuploid, and had various levels of tumorigenic potential. The biological and genetic properties of these lines are distinct from those found in most hyperplastic alveolar outgrowth lines, the form of mammary preneoplasia occurring in most traditional models of murine mammary tumorigenesis. These results indicate that the preneoplastic cell populations found in this genetically engineered model are similar in biological properties to a subset of precurser lesions found in human breast cancer and provide a unique model to identify secondary events critical for tumorigenicity and invasiveness.

  12. Histochemical properties of bovine and ovine mammary glands during fetal development.

    PubMed

    Hara, Asuka; Abe, Tomoyuki; Hirao, Atsushi; Sanbe, Kazuhiro; Ayakawa, Hiromichi; Sarantonglaga, Borjigin; Yamaguchi, Mio; Sato, Akane; Khurchabilig, Atchalalt; Ogata, Kazuko; Fukumori, Rika; Sugita, Shoei; Nagao, Yoshikazu

    2018-02-20

    In order to obtain more information on the development of bovine and ovine fetal mammary glands, a series of mammary glands from fetuses of different ages were analyzed. A total of 16 bovine fetuses with curved crown rump lengths ranging from 12 cm (80 days) to 75 cm (240 days) and 15 ovine fetuses ranging from 55 days to 131 days were examined. We used hematoxylin and eosin stain and Oil-Red-O stain to analyze the developmental and morphogenetic processes of mammary glands. In addition, we used immunohistochemical staining to determine the pattern of expression of cytokeratin 18 (CK18) during luminal epithelial differentiation, α-smooth-muscle actin (α-SMA) for myoepithelial differentiation, Ki-67 for cell proliferation, and estrogen receptor α (ERα). Our analyzes showed: (a) The primary mammary duct begin to proliferate in a lengthwise within the teat at 90 days in bovine fetuses and 63 days in ovine fetus; (b) luminal epithelial cells and myoepithelial cells appeared from 90 days in bovine fetuses and 63 days in ovine fetus; (c) proliferation of epithelial cells appeared to coincide with the development of the primary and secondary ducts; and (d) ERα was not found in the fetal mammary gland, but adipocytes showed the presence of ERα. Overall, these results indicate that the sequence of events in the prenatal development of the mammary gland of sheep is similar to that of cattle.

  13. Histochemical properties of bovine and ovine mammary glands during fetal development

    PubMed Central

    HARA, Asuka; ABE, Tomoyuki; HIRAO, Atsushi; SANBE, Kazuhiro; AYAKAWA, Hiromichi; SARANTONGLAGA, Borjigin; YAMAGUCHI, Mio; SATO, Akane; KHURCHABILIG, Atchalalt; OGATA, Kazuko; FUKUMORI, Rika; SUGITA, Shoei; NAGAO, Yoshikazu

    2017-01-01

    In order to obtain more information on the development of bovine and ovine fetal mammary glands, a series of mammary glands from fetuses of different ages were analyzed. A total of 16 bovine fetuses with curved crown rump lengths ranging from 12 cm (80 days) to 75 cm (240 days) and 15 ovine fetuses ranging from 55 days to 131 days were examined. We used hematoxylin and eosin stain and Oil-Red-O stain to analyze the developmental and morphogenetic processes of mammary glands. In addition, we used immunohistochemical staining to determine the pattern of expression of cytokeratin 18 (CK18) during luminal epithelial differentiation, α-smooth-muscle actin (α-SMA) for myoepithelial differentiation, Ki-67 for cell proliferation, and estrogen receptor α (ERα). Our analyzes showed: (a) The primary mammary duct begin to proliferate in a lengthwise within the teat at 90 days in bovine fetuses and 63 days in ovine fetus; (b) luminal epithelial cells and myoepithelial cells appeared from 90 days in bovine fetuses and 63 days in ovine fetus; (c) proliferation of epithelial cells appeared to coincide with the development of the primary and secondary ducts; and (d) ERα was not found in the fetal mammary gland, but adipocytes showed the presence of ERα. Overall, these results indicate that the sequence of events in the prenatal development of the mammary gland of sheep is similar to that of cattle. PMID:29249731

  14. Learning curve of office-based ultrasonography for rotator cuff tendons tears.

    PubMed

    Ok, Ji-Hoon; Kim, Yang-Soo; Kim, Jung-Man; Yoo, Tae-Wook

    2013-07-01

    To compare the accuracy of ultrasonography and MR arthrography (MRA) imaging in detecting of rotator cuff tears with arthroscopic finding used as the reference standard. The ultrasonography and MRA findings of 51 shoulders that underwent the arthroscopic surgery were prospectively analysed. Two orthopaedic doctors independently performed ultrasonography and interpreted the findings at the office. The tear size measured at ultrasonography and MRA was compared with the size measured at surgery using Pearson correlation coefficients (r). The sensitivity, specificity, accuracy, positive predictive value, negative predictive value and false-positive rate were calculated for a diagnosis of partial-and full-thickness rotator cuff tears. The kappa coefficient was calculated to verify the inter-observer agreement. The sensitivity of ultrasonography and MRA for detecting partial-thickness tears was 45.5 and 72.7 %, and that for full-thickness tears was 80.0 and 100 %, respectively. The accuracy of ultrasonograpy and MRA for detecting partial-thickness tears was 45.1 and 88.2 %, and that for full-thickness tears was 82.4 and 98 %, respectively. Tear size measured based on ultrasonography examination showed a poor correlation with the size measured at arthroscopic surgery (r = 0.21; p < 0.05). However, tear size estimated by MRA showed a strong correlation (r = 0.75; p < 0.05). The kappa coefficient was 0.47 between the two independent examiners. The accuracy of office-based ultrasonography for beginner orthopaedic surgeons to detect full-thickness rotator cuff tears was comparable to that of MRA but was less accurate for detecting partial-thickness tears and torn size measurement. Inter-observer agreement on the interpretation was fair. These results highlight the importance of the correct technique and experience in operation of ultrasonography in shoulder joint. Diagnostic study, Level II.

  15. Diagnostic accuracy of transabdominal ultrasonography for gallbladder polyps: systematic review.

    PubMed

    Martin, Erin; Gill, Richdeep; Debru, Estifanos

    2018-06-01

    Previous research has shown variable but generally poor accuracy of transabdominal ultrasonography in the diagnosis of gallbladder polyps. We performed a systematic review of the literature with the aim of helping surgeons interpret and apply these findings in the preoperative assessment and counselling of their patients. We searched PubMed, MEDLINE and the Cochrane database using the keywords "gallbladder," "polyp," "ultrasound," "pathology" and "diagnosis" for English-language articles published after 1990 with the full-text article available through our institutional subscriptions. Polyps were defined as immobile features that on transabdominal ultrasonography appear to arise from the mucosa and that lack an acoustic shadow, and pseudopolyps were defined as features such as inflammation, hyperplasia, cholesterolosis and adenomyomatosis that convey no risk of malignant transformation. The search returned 1816 articles, which were narrowed down to 14 primary sources involving 15 497 (range 23-13 703) patients who had preoperative transabdominal ultrasonography, underwent cholecystectomy and had postoperative pathology results available. Among the 1259 patients in whom a gallbladder polyp was diagnosed on ultrasonography, 188 polyps were confirmed as true polyps on pathologic examination, and 81 of these were found to be malignant. Of the 14 238 patients for whom a polyp was not seen on ultrasonography, 38 had a true polyp on pathologic examination, none of which were malignant. For true gallbladder polyps, transabdominal ultrasonography had a sensitivity of 83.1%, specificity of 96.3%, positive predictive value of 14.9% (7.0% for malignant polyps) and negative predictive value of 99.7%. Transabdominal ultrasonography has a high false-positive rate (85.1%) for the diagnosis of gallbladder polyps. Further study of alternative imaging modalities and reevaluation of existing management guidelines are warranted.

  16. INDUCTION OF MAMMARY GLAND DEVELOPMENT IN ESTROGEN RECEPTOR-ALPHA KNOCKOUT MICE

    EPA Science Inventory

    Mammary glands from the estrogen receptor knockout ( ERKO) mouse do not undergo ductal morphogenesis or alveolar development. Disrupted Er signaling may result in reduced estrogen-responsive gene products in the mammary gland or reduced mammotropic hormones that contribute t...

  17. Gestational high-fat diet and bisphenol A exposure heightens mammary cancer risk

    PubMed Central

    Leung, Yuet-Kin; Govindarajah, Vinothini; Cheong, Ana; Veevers, Jennifer; Song, Dan; Gear, Robin; Zhu, Xuegong; Ying, Jun; Kendler, Ady; Medvedovic, Mario; Belcher, Scott

    2017-01-01

    In utero exposure to bisphenol A (BPA) increases mammary cancer susceptibility in offspring. High-fat diet is widely believed to be a risk factor of breast cancer. The objective of this study was to determine whether maternal exposure to BPA in addition to high-butterfat (HBF) intake during pregnancy further influences carcinogen-induced mammary cancer risk in offspring, and its dose–response curve. In this study, we found that gestational HBF intake in addition to a low-dose BPA (25 µg/kg BW/day) exposure increased mammary tumor incidence in a 50-day-of-age chemical carcinogen administration model and altered mammary gland morphology in offspring in a non-monotonic manner, while shortening tumor-free survival time compared with the HBF-alone group. In utero HBF and BPA exposure elicited differential effects at the gene level in PND21 mammary glands through DNA methylation, compared with HBF intake in the absence of BPA. Top HBF + BPA-dysregulated genes (ALDH1B1, ASTL, CA7, CPLX4, KCNV2, MAGEE2 and TUBA3E) are associated with poor overall survival in The Cancer Genomic Atlas (TCGA) human breast cancer cohort (n = 1082). Furthermore, the prognostic power of the identified genes was further enhanced in the survival analysis of Caucasian patients with estrogen receptor-positive tumors. In conclusion, concurrent HBF dietary and a low-dose BPA exposure during pregnancy increases mammary tumor incidence in offspring, accompanied by alterations in mammary gland development and gene expression, and possibly through epigenetic reprogramming. PMID:28487351

  18. Xeroradiography and ultrasonography in the evaluation of a penile injury.

    PubMed

    Oesterling, J E; Bromberg, W D; Albertsen, P C

    1986-04-01

    A 34-year-old white man presented with severe penile cellulitis following injection of epoxy glue into the shaft of the penis. Preoperative xeroradiography and ultrasonography localized the hardened masses of glue to the left corpus cavernosum and subcutaneous tissues. Under the guidance of intraoperative ultrasonography this foreign material was removed surgically. Postoperatively, the cellulitis resolved promptly and xeroradiography demonstrated no residual fragments. Although various modalities, including computerized tomography and roentgenography, are available to detect foreign bodies in soft tissues, xeroradiography and ultrasonography are ideally suited for use in the male external genitalia.

  19. Effects of milk replacer formulation on measures of mammary growth and composition in Holstein heifers.

    PubMed

    Daniels, K M; Capuco, A V; McGilliard, M L; James, R E; Akers, R M

    2009-12-01

    Overfeeding prepubertal heifers may impair mammary parenchymal growth and reduce milk production, but evidence suggests that increased intake of a high-protein milk replacer before weaning may be beneficial. This study was designed to evaluate effects of milk replacer (MR) composition on mass and composition of mammary parenchyma and fat pad, growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis gene expression, and putative mammary epithelial stem cells. Specifically, we hypothesized that positive effects of faster rates of gain during the preweaning period alter the development, persistence, or activity of populations of putative mammary epithelial stem cells, possibly through involvement of GH/IGF-I axis molecules. Twenty-four newborn heifers were fed 1 of 4 MR diets (n = 6/diet): control [20% crude protein (CP), 21% fat MR fed at 441 g of dry matter (DM)/d], high protein, low fat (28% CP, 20% fat MR fed at 951 g of DM/d), high protein, high fat (27% CP, 28% fat MR fed at 951 g of DM/d), and high protein, high fat+ (27% CP, 28% fat MR fed at 1,431 g of DM/d). Water and starter (20% CP, 1.43% fat) were offered ad libitum. Animals were killed on d 65 and mammary tissue was subjected to biochemical, molecular, and histological examination. No differences in mammary parenchymal mass or composition, with or without adjusting for empty body weight, were detected. Mass was increased and composition of the mammary fat pad was altered by nutrient intake. No diet differences in putative mammary epithelial stem cell abundance or abundance of transcripts for genes of the GH/IGF-I axis were detected. In this study, growth of the mammary epithelium, size of the mammary epithelial stem cell population, and components of the GH/IGF-I axis did not depend on diet. However, an underlying positive correlation between telomerase, a marker of mammary stem cells, and growth of the mammary parenchyma was detected. Implications of diet-induced effects on mammary fat pad and

  20. ApcMin, A Mutation in the Murine Apc Gene, Predisposes to Mammary Carcinomas and Focal Alveolar Hyperplasias

    NASA Astrophysics Data System (ADS)

    Moser, Amy Rapaich; Mattes, Ellen M.; Dove, William F.; Lindstrom, Mary J.; Haag, Jill D.; Gould, Michael N.

    1993-10-01

    ApcMin (Min, multiple intestinal neoplasia) is a point mutation in the murine homolog of the APC gene. Min/+ mice develop multiple intestinal adenomas, as do humans carrying germ-line mutations in APC. Female mice carrying Min are also prone to develop mammary tumors. Min/+ mammary glands are more sensitive to chemical carcinogenesis than are +/+ mammary glands. Transplantation of mammary cells from Min/+ or +/+ donors into +/+ hosts demonstrates that the propensity to develop mammary tumors is intrinsic to the Min/+ mammary cells. Long-term grafts of Min/+ mammary glands also gave rise to focal alveolar hyperplasias, indicating that the presence of the Min mutation also has a role in the development of these lesions.

  1. Mammary stem cells and the differentiation hierarchy: current status and perspectives

    PubMed Central

    Visvader, Jane E.; Stingl, John

    2014-01-01

    The mammary epithelium is highly responsive to local and systemic signals, which orchestrate morphogenesis of the ductal tree during puberty and pregnancy. Based on transplantation and lineage tracing studies, a hierarchy of stem and progenitor cells has been shown to exist among the mammary epithelium. Lineage tracing has highlighted the existence of bipotent mammary stem cells (MaSCs) in situ as well as long-lived unipotent cells that drive morphogenesis and homeostasis of the ductal tree. Moreover, there is accumulating evidence for a heterogeneous MaSC compartment comprising fetal MaSCs, slow-cycling cells, and both long-term and short-term repopulating cells. In parallel, diverse luminal progenitor subtypes have been identified in mouse and human mammary tissue. Elucidation of the normal cellular hierarchy is an important step toward understanding the “cells of origin” and molecular perturbations that drive breast cancer. PMID:24888586

  2. Proliferation of human mammary cancer cells exposed to 27-hydroxycholesterol

    PubMed Central

    CRUZ, PAMELA; TORRES, CRISTIAN; RAMÍREZ, MARÍA EUGENIA; EPUÑÁN, MARÍA JOSÉ; VALLADARES, LUIS EMILIO; SIERRALTA, WALTER DANIEL

    2010-01-01

    The aim of the present study was to identify the possible mechanisms by which certain estradiol receptor (ER)-positive mammary tumor cells remain resistant to treatment with anti-estrogens or inhibitors of local estradiol (E2) production. To this end, we compared the proliferative effects on mammary cancer cells of the novel selective ER modulator 27-hydroxycholesterol (27OHC) to those of E2, and evaluated their inhibition by ICI 182,780 (ICI). Analysis of the effects on the cell cycle of 27OHC and E2 in the absence or presence of ICI was conducted. In ER-positive mammary tumor cells, we detected the blocking of 27OHC proliferation-stimulatory activity by simvastatin, as well as the inhibition of E2-stimulated proliferation by an α-fetoprotein-derived cyclic nonapeptide. The effects reported herein may be extrapolated to infiltrating mammary cancer, where the activity of local macrophages may stimulate tumor growth. We suggest that increased breast cancer growth in obese patients may be related to increased 27OHC circulatory levels. PMID:22993572

  3. Proliferation of human mammary cancer cells exposed to 27-hydroxycholesterol.

    PubMed

    Cruz, Pamela; Torres, Cristian; Ramírez, María Eugenia; Epuñán, María José; Valladares, Luis Emilio; Sierralta, Walter Daniel

    2010-05-01

    The aim of the present study was to identify the possible mechanisms by which certain estradiol receptor (ER)-positive mammary tumor cells remain resistant to treatment with anti-estrogens or inhibitors of local estradiol (E(2)) production. To this end, we compared the proliferative effects on mammary cancer cells of the novel selective ER modulator 27-hydroxycholesterol (27OHC) to those of E(2), and evaluated their inhibition by ICI 182,780 (ICI). Analysis of the effects on the cell cycle of 27OHC and E(2) in the absence or presence of ICI was conducted. In ER-positive mammary tumor cells, we detected the blocking of 27OHC proliferation-stimulatory activity by simvastatin, as well as the inhibition of E(2)-stimulated proliferation by an α-fetoprotein-derived cyclic nonapeptide. The effects reported herein may be extrapolated to infiltrating mammary cancer, where the activity of local macrophages may stimulate tumor growth. We suggest that increased breast cancer growth in obese patients may be related to increased 27OHC circulatory levels.

  4. Point-of-care ultrasonography by pediatric emergency physicians. Policy statement.

    PubMed

    Marin, Jennifer R; Lewiss, Resa E

    2015-04-01

    Point-of-care ultrasonography is increasingly being used to facilitate accurate and timely diagnoses and to guide procedures. It is important for pediatric emergency physicians caring for patients in the emergency department to receive adequate and continued point-of-care ultrasonography training for those indications used in their practice setting. Emergency departments should have credentialing and quality assurance programs. Pediatric emergency medicine fellowships should provide appropriate training to physician trainees. Hospitals should provide privileges to physicians who demonstrate competency in point-of-care ultrasonography. Ongoing research will provide the necessary measures to define the optimal training and competency assessment standards. Requirements for credentialing and hospital privileges will vary and will be specific to individual departments and hospitals. As more physicians are trained and more research is completed, there should be one national standard for credentialing and privileging in point-of-care ultrasonography for pediatric emergency physicians.

  5. Progesterone receptor isoforms in the mammary gland of cats and dogs.

    PubMed

    Gracanin, A; de Gier, J; Zegers, K; Bominaar, M; Rutteman, G R; Schaefers-Okkens, A C; Kooistra, H S; Mol, J A

    2012-12-01

    Progesterone exerts its effect by binding to specific progesterone receptors (PR) within the cell. In dogs and cats, no data are available on PR isoforms as found in other species. We therefore investigated the sequence of the PR gene and encoded protein in dogs and cats, the expression of PR isoforms in mammary tissue using Western blots and the presence of PR in mammary tissue using immunohistochemistry. Comparison of the amino acid sequence of the canine and feline PR with human PR revealed major differences in the PR-B-specific upstream segment (BUS). However, the essential activation function 3 (AF3) domain was intact in the cat but mutated in the dog. The DNA and ligand-binding domains were highly similar among the species. In cats with fibroadenomatous hyperplasia (FAH), high expression of PR mRNA together with growth hormone (GH), GH receptor (GHR) and IGF-I mRNA was found in comparison with feline mammary carcinomas. Immunohistochemical analysis showed strong nuclear as well as cytoplasmic staining for PR in FAH. Western blot analysis revealed expression of the PR-A and PR-B isoforms in the feline mammary gland. In canine mammary tissue, the most abundant PR staining was found in proliferative zones of the mammary gland. Western blot analyses showed mainly staining for PR-A with lower PR-B staining. It is concluded that in dogs and cats both PR isoforms are expressed. The role of mutations found in the canine PR-B is discussed. © 2012 Blackwell Verlag GmbH.

  6. Evaluation of serum haptoglobin and C-reactive protein in dogs with mammary tumors.

    PubMed

    Planellas, Marta; Bassols, Anna; Siracusa, Carlo; Saco, Yolanda; Giménez, Mercè; Pato, Raquel; Pastor, Josep

    2009-09-01

    In veterinary medicine, there is increasing interest in measuring acute phase proteins as a tool in the diagnosis and monitoring of neoplastic diseases. Although mammary neoplasms are the most common type of cancer in dogs, acute phase proteins have not been extensively evaluated in dogs with mammary tumors. The aim of this study was to evaluate serum haptoglobin (Hp) and C-reactive protein (CRP) concentrations in the dogs with mammary tumors and assess their potential association with malignancy. A retrospective study of dogs with mammary tumors was performed. Serum concentrations of CRP and Hp were determined in healthy control dogs (n=20) and dogs with mammary tumors before surgery (n=41). Mammary tumors were grouped as carcinomas (n=24), fibrosarcoma (n=1), malignant mixed tumors (n=7), benign mixed tumors (n=6), and adenomas (n=3). CRP and Hp concentrations were compared in dogs with different tumor types and were also compared based on tumor size, lymph node infiltration, skin ulceration, fixation to underlying tissue, and time between tumor identification and removal. Hp concentration was significantly (P<.043) higher in dogs with mammary tumors (median 2.03 g/L, range 0.09-2.94 g/L) compared with controls (1.38 g/L, range 0.08-3.00 g/L), but the range of values overlapped considerably. CRP concentration was higher in dogs with carcinomas (4.70 mg/L, range 0.63-128.96 mg/L) vs controls (2.11 mg/L, range 0.25-6.57 mg/L) (P=.0008) and in dogs with ulcerated skin (14.8 mg/L, range 5.7-128.9 mg/L, n=3) compared with those without ulceration (2.4 mg/L, range 0.11-30.3 mg/L, n=38) (P=.048). Serum Hp and CRP do not appear to have value in diagnosing or predicting malignancy of mammary tumors in dogs. Higher CRP concentrations in dogs with mammary carcinoma suggest a role for inflammation in this tumor type.

  7. From Genes to Milk: Genomic Organization and Epigenetic Regulation of the Mammary Transcriptome

    PubMed Central

    Lemay, Danielle G.; Pollard, Katherine S.; Martin, William F.; Freeman Zadrowski, Courtneay; Hernandez, Joseph; Korf, Ian; German, J. Bruce; Rijnkels, Monique

    2013-01-01

    Even in genomes lacking operons, a gene's position in the genome influences its potential for expression. The mechanisms by which adjacent genes are co-expressed are still not completely understood. Using lactation and the mammary gland as a model system, we explore the hypothesis that chromatin state contributes to the co-regulation of gene neighborhoods. The mammary gland represents a unique evolutionary model, due to its recent appearance, in the context of vertebrate genomes. An understanding of how the mammary gland is regulated to produce milk is also of biomedical and agricultural importance for human lactation and dairying. Here, we integrate epigenomic and transcriptomic data to develop a comprehensive regulatory model. Neighborhoods of mammary-expressed genes were determined using expression data derived from pregnant and lactating mice and a neighborhood scoring tool, G-NEST. Regions of open and closed chromatin were identified by ChIP-Seq of histone modifications H3K36me3, H3K4me2, and H3K27me3 in the mouse mammary gland and liver tissue during lactation. We found that neighborhoods of genes in regions of uniquely active chromatin in the lactating mammary gland, compared with liver tissue, were extremely rare. Rather, genes in most neighborhoods were suppressed during lactation as reflected in their expression levels and their location in regions of silenced chromatin. Chromatin silencing was largely shared between the liver and mammary gland during lactation, and what distinguished the mammary gland was mainly a small tissue-specific repertoire of isolated, expressed genes. These findings suggest that an advantage of the neighborhood organization is in the collective repression of groups of genes via a shared mechanism of chromatin repression. Genes essential to the mammary gland's uniqueness are isolated from neighbors, and likely have less tolerance for variation in expression, properties they share with genes responsible for an organism's survival

  8. Mouse mammary tumour virus (MMTV) and human breast cancer with neuroendocrine differentiation.

    PubMed

    Js, Lawson; Cc, Ngan; Wk, Glenn; Dd, Tran

    2017-01-01

    Mouse mammary tumour viruses (MMTVs) may have a role in a subset of human breast cancers. MMTV positive human breast cancers have similar histological characteristics to neuroendocrine breast cancers and to MMTV positive mouse mammary tumours. The purpose of this study was to investigate the expression of neuroendocrine biomarkers - synaptophysin and chromogranin, to determine if these histological characteristics and biomarker expression were due to the influences of MMTV. Immunohistochemistry analyses to identify synaptophysin and chromogranin were conducted on a series of human breast cancers in which (i) MMTV had been previously identified and had similar histological characteristics to MMTV positive mouse mammary tumours and (ii) MMTV positive mouse mammary tumours. The expression of synaptophysin and chromogranin in MMTV positive mouse mammary tumors were all positive (7 of 7 specimens - 100% positive). The expression of synaptophysin and chromogranin in MMTV positive human breast cancers was much less prevalent (3 of 22 - 14%). There was no expression of synaptophysin and chromogranin in the normal breast tissue control specimens. It is not possible to draw any firm conclusions from these observations. However, despite the small numbers of MMTV positive mouse mammary tumours in this study, the universal expression in these specimens of synaptophysin and chromogranin proteins is striking. This pattern of synaptophysin and chromogranin expression is very different from their expression in MMTV positive human breast cancers. The reason for these differences is not known. The high prevalence of positive expression of synaptophysin and chromogranin in MMTV positive mouse mammary tumours and low expression of synaptophysin and chromogranin in MMTV positive human breast cancers indicates that MMTV is not usually associated with neuroendocrine human breast cancers.

  9. Mammary development, hyperestrogenemia, and hypocortisolemia in a male cat with an adrenal cortical carcinoma.

    PubMed

    Nadolski, Amy C; Markovich, Jessica E; Jennings, Samuel H; Mahony, Orla M

    2016-10-01

    A 14-year-old neutered male domestic shorthaired cat was diagnosed with an adrenal cortical carcinoma causing hyperestrogenemia that resulted in mammary hyperplasia and sexual behavior. A right adrenalectomy and mammary gland biopsy were performed. Adrenal cortical neoplasia should be ruled out in any neutered male cat with mammary development and/or exhibiting sexual behavior.

  10. Expression of novel, putative stem cell markers in prepubertal and lactating mammary glands of bovine

    USDA-ARS?s Scientific Manuscript database

    Mammary stem cells (MaSC) are essential for growth and maintenance of the mammary epithelium. Two main phases of mammary growth include ductal elongation prior to puberty and lobulo-alveolar growth and development during pregnancy. Some studies have utilized morphological characteristics and retenti...

  11. Genistein and resveratrol: mammary cancer chemoprevention and mechanisms of action in the rat.

    PubMed

    Whitsett, Timothy G; Lamartiniere, Coral A

    2006-12-01

    The environment, including diet, plays a critical role in a woman's subsequent risk of breast cancer. Two dietary polyphenols that have received attention from the health and research communities for their ability to protect against breast cancer are: genistein, a component of soy; and resveratrol, a phytoalexin found in red grapes and red wine. We and others have shown that both genistein and resveratrol can protect against mammary cancer in rodents. The timing of exposure to genistein appears critical for its mammary protective effects. It has been reported that genistein early in life causes enhanced mammary gland differentiation, alterations in cell proliferation and apoptosis, and upregulation of tumor-suppressor genes. With resveratrol in the diet, changes in cell proliferation and apoptosis in terminal ductal structures of the mammary gland might help to explain its protective effects. We conclude that genistein and resveratrol can protect against breast cancer by regulating important mammary growth and differentiation pathways.

  12. Polyurethane-covered mammary implants: a 12-year experience.

    PubMed

    Gasperoni, C; Salgarello, M; Gargani, G

    1992-10-01

    Polyurethane-covered mammary implants are the implants of choice in aesthetic and reconstructive mammary surgery. These implants give very good results in regard to breast contour and consistency, and have a very low complication rate. We present our 12-year experience using polyurethane-covered prostheses. We place the implant mostly in the subglandular or subcutaneous site, and their capsular contracture rate is extremely low (3.3%). Based on our experience, we also review the other complications and side effects occurring with polyurethane prostheses and discuss them in detail.

  13. The contribution of growth hormone to mammary neoplasia

    PubMed Central

    Perry, Jo K; Mohankumar, Kumarasamypet M; Emerald, B Starling; Mertani, Hichem C; Lobie, Peter E

    2008-01-01

    While the effects of growth hormone (GH) on longitudinal growth are well established, the observation that GH contributes to neoplastic progression is more recent. Accumulating literature implicates GH-mediated signal transduction in the development and progression of a wide range malignancies including breast cancer. Recently autocrine human GH been demonstrated to be an orthotopically expressed oncogene for the human mammary gland. This review will highlight recent evidence linking GH and mammary carcinoma and discuss GH-antagonism as a potential therapeutic approach for treatment of breast cancer. PMID:18253708

  14. Human Breast Cancer Cells Are Redirected to Mammary Epithelial Cells upon Interaction with the Regenerating Mammary Gland Microenvironment In-Vivo

    PubMed Central

    Bussard, Karen M.; Smith, Gilbert H.

    2012-01-01

    Breast cancer is the second leading cause of cancer deaths in the United States. At present, the etiology of breast cancer is unknown; however the possibility of a distinct cell of origin, i.e. a cancer stem cell, is a heavily investigated area of research. Influencing signals from the tissue niche are known to affect stem cells. Literature has shown that cancer cells lose their tumorigenic potential and display ‘normal’ behavior when placed into ‘normal’ ontogenic environments. Therefore, it may be the case that the tissue microenvironment is able to generate signals to redirect cancer cell fate. Previously, we showed that pluripotent human embryonal carcinoma cells could be redirected by the regenerating mammary gland microenvironment to contribute epithelial progeny for ‘normal’ gland development in-vivo. Here, we show that that human metastatic, non-metastatic, and metastasis-suppressed breast cancer cells proliferate and contribute to normal mammary gland development in-vivo without tumor formation. Immunochemistry for human-specific mitochondria, keratin 8 and 14, as well as human-specific milk proteins (alpha-lactalbumin, impregnated transplant hosts) confirmed the presence of human cell progeny. Features consistent with normal mammary gland development as seen in intact hosts (duct, lumen formation, development of secretory acini) were recapitulated in both primary and secondary outgrowths from chimeric implants. These results suggest the dominance of the tissue microenvironment over cancer cell fate. This work demonstrates that cultured human breast cancer cells (metastatic and non-metastatic) respond developmentally to signals generated by the mouse mammary gland microenvironment during gland regeneration in-vivo. PMID:23155468

  15. Mammary development, hyperestrogenemia, and hypocortisolemia in a male cat with an adrenal cortical carcinoma

    PubMed Central

    Nadolski, Amy C.; Markovich, Jessica E.; Jennings, Samuel H.; Mahony, Orla M.

    2016-01-01

    A 14-year-old neutered male domestic shorthaired cat was diagnosed with an adrenal cortical carcinoma causing hyperestrogenemia that resulted in mammary hyperplasia and sexual behavior. A right adrenalectomy and mammary gland biopsy were performed. Adrenal cortical neoplasia should be ruled out in any neutered male cat with mammary development and/or exhibiting sexual behavior. PMID:27708447

  16. Characterization of microRNA profile in mammary tissue of dairy and beef breed heifers.

    PubMed

    Wicik, Z; Gajewska, M; Majewska, A; Walkiewicz, D; Osińska, E; Motyl, T

    2016-02-01

    MicroRNAs (miRNAs) are small non-coding RNAs that participate in the regulation of gene expression. Their role during mammary gland development is still largely unknown. In this study, we performed a microarray analysis to identify miRNAs associated with high mammogenic potential of the bovine mammary gland. We identified 54 significantly differentially expressed miRNAs between the mammary tissue of dairy (Holstein-Friesian, HF) and beef (Limousin, LM) postpubertal heifers. Fifty-two miRNAs had higher expression in the mammary tissue of LM heifers. The expression of the top candidate miRNAs (bta-miR-10b, bta-miR-29b, bta-miR-101, bta-miR-375, bta-miR-2285t, bta-miR-146b, bta-let7b, bta-miR-107, bta-miR-1434-3p) identified in the microarray experiment was additionally evaluated by qPCR. Enrichment analyses for targeted genes revealed that the major differences between miRNA expression in the mammary gland of HF versus LM were associated with the regulation of signalling pathways that are crucial for mammary gland development, such as TGF-beta, insulin, WNT and inflammatory pathways. Moreover, a number of genes potentially targeted by significantly differentially expressed miRNAs were associated with the activity of mammary stem cells. These data indicate that the high developmental potential of the mammary gland in dairy cattle, leading to high milk productivity, depends also on a specific miRNA expression pattern. © 2015 Blackwell Verlag GmbH.

  17. Clinical utility of colour flow Doppler ultrasonography in planning anterolateral thigh flap harvest.

    PubMed

    Patel, Rajan S; Higgins, Kevin M; Enepekides, Danny J; Hamilton, Paul A

    2010-10-01

    The anatomic variability of cutaneous perforators contributes to the technical challenges of anterolateral thigh (ALT) free flap harvest. The objective of this study was to assess the accuracy and clinical utility of preoperative colour flow Doppler (CFD) ultrasonography in evaluating planned ALT flap donor sites. A prospective study of the infrainguinal vasculature (profunda femoris and lateral circumflex femoral arteries) in 16 consecutive patients scheduled for ALT free flap transfer for reconstruction of head and neck surgical defects was undertaken. All patients underwent CFD ultrasonography. The location of perforators and the thigh thickness determined by CFD ultrasonography were correlated with the actual intraoperative findings using a scatter plot and paired t-test. Two patients were diagnosed with bilateral silent infrainguinal claudication, which precluded safe use of the ALT donor site. In two other patients, the planned ALT donor site ipsilateral to the defect was not used because of silent infrainguinal claudication diagnosed by CFD ultrasonography. In the 14 patients who underwent ALT flap harvest, CFD ultrasonography identified 48 perforators, which coincided with 43 actual perforators found intraoperatively. CFD ultrasonography demonstrated a statistically significant correlation with the actual perforator locations (Spearman coefficient .76; p = .55). Although CFD ultrasonography tended to underestimate flap thickness, there was a statistically significant correlation (Spearman coefficient .94; p ≤ .0001) with the actual flap thickness. CFD ultrasonography has clinical utility in facilitating decision making and planning ALT flap harvest.

  18. Precocious mammary development in an 8-month-old Holstein heifer

    PubMed Central

    Ambrose, Divakar J.; Emmanuel, Daya G.V.

    2008-01-01

    An 8-month-old, virgin Holstein heifer with precocious mammary development was presented for examination. Protein, fat, and lactose in the mammary secretion were 14.90%, 0.12%, and 0.20%, respectively; somatic cell count was 3.9 × 106/mL, with no bacterial infection. The heifer was inseminated at 15 months of age, confirmed pregnant, and subsequently slaughtered. PMID:18978977

  19. Reliability, validity and feasibility of nail ultrasonography in psoriatic arthritis.

    PubMed

    Arbault, Anaïs; Devilliers, Hervé; Laroche, Davy; Cayot, Audrey; Vabres, Pierre; Maillefert, Jean-Francis; Ornetti, Paul

    2016-10-01

    To determine the feasibility, reliability and validity of nails ultrasonography in psoriatic arthritis as an outcome measure. Pilot prospective single-centre study of eight ultrasonography parameters in B mode and power Doppler concerning the distal interphalangeal (DIP) joint, the matrix, the bed and nail plate. Intra-observer and inter-observer reliability was evaluated for the seven quantitative parameters (ICC and kappa). Correlations between ultrasonography and clinical variables were searched to assess external validity. Feasibility was assessed by the time to carry out the examination and the percentage of missing data. Twenty-seven patients with psoriatic arthritis (age 55.0±16.2 years, disease duration 13.4±9.4 years) were included. Of these, 67% presented nail involvement on ultrasonography vs 37% on physical examination (P<0.05). Reliability was good (ICC and weighted kappa>0.75) for the seven quantitative parameters, except for synovitis of the DIP joint in B mode. The synovitis of the DIP joint revealed by ultrasonography correlated with the total number of clinical synovitis and Doppler US of the nail (matrix and bed). Doppler US of the matrix correlated with VAS pain but not with the ASDAS-CRP or with clinical enthesitis. No significant correlation was found with US nail thickness. The feasibility and reliability of ultrasonography of the nail in psoriatic arthritis appear to be satisfactory. Among the eight parameters evaluated, power Doppler of the matrix which correlated with local inflammation (DIP joint and bed) and with VAS pain could become an interesting outcome measure, provided that it is also sensitive to change. Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  20. Diagnostic utility of abdominal ultrasonography in dogs with chronic diarrhea.

    PubMed

    Leib, M S; Larson, M M; Grant, D C; Monroe, W E; Troy, G C; Panciera, D L; Rossmeisl, J H; Werre, S R

    2012-01-01

    Chronic diarrhea is common in dogs and has many causes. Ultrasonographic descriptions of many gastrointestinal diseases have been published, but the diagnostic utility of ultrasonography in dogs with chronic diarrhea has not been investigated. Diagnostic utility of abdominal ultrasound will be highest in dogs with GI neoplasia and lowest in those with inflammatory disorders. 87 pet dogs with chronic diarrhea. Prospective study in which medical records were reviewed and contribution of abdominal ultrasound toward making diagnosis was scored. In 57/87 (66%) of dogs, the same diagnosis would have been reached without ultrasonography. In 13/87 (15%) of dogs, the ultrasound examination was vital or beneficial to making the diagnosis. Univariable analysis identified that increased diagnostic utility was associated with weight loss (P = .0086), palpation of an abdominal or rectal mass (P = .0031), diseases that commonly have mass lesions visible on ultrasound examination (P < .0001), and a final diagnosis of GI neoplasia. Multivariable regression indicated that utility of abdominal ultrasonography would be 30 times more likely to be high in dogs in which an abdominal or rectal mass was palpated (odds ratio 30.5, 95% CI 5.5-169.6) (P < .0001) versus dogs without a palpable mass. In 15/87 (17%) of dogs, additional benefits of ultrasonography to case management, independent of the contribution to the diagnosis of diarrhea, were identified. Overall, the diagnostic utility of abdominal ultrasonography was low in dogs with chronic diarrhea. Identification of factors associated with high diagnostic utility is an indication to perform abdominal ultrasonography in dogs with chronic diarrhea. Copyright © 2012 by the American College of Veterinary Internal Medicine.

  1. Maternal handling during pregnancy reduces DMBA-induced mammary tumorigenesis among female offspring.

    PubMed Central

    Hilakivi-Clarke, L.

    1997-01-01

    The present study investigated whether handling of pregnant rats would affect mammary tumorigenesis in their female offspring. Pregnant Sprague-Dawley rats were injected daily with 0.05 ml of vehicle between days 14 and 20 of gestation or were left undisturbed. Handling did not have any effects on pregnancy or early development of the offspring. The female offspring were administered 10 mg of 7,12-dimethylbenz(a)anthracene (DMBA) at the age of 55 days. The rats whose mothers were handled during pregnancy had a significantly reduced mammary tumour incidence when compared with the offspring of non-handled mothers. Thus, on week 18 after DMBA exposure, 15% of the handled offspring had developed mammary tumours, whereas 44% of the non-handled offspring had tumours. No significant differences in the latency to tumour appearance, in the size of the tumours or in their growth rates were noted. Daily handling performed during post-natal days 5 and 20 produced similar data to that obtained for prenatal handling; on week 18 after DMBA exposure, the mammary tumour incidence among the post-natally handled rats was 22% and among the non-handled rats 44%. Possible deviations in hormonal parameters were also studied in adult female rats exposed in utero to handling. The onset of puberty tended to occur later among the handled offspring, but no differences in the uterine wet weights or serum oestradiol levels between the groups were noted. In conclusion, maternal handling reduced the offspring's risk to develop mammary tumours, and this effect was independent of the oestrogenic environment at adulthood. We propose that handling of a pregnant rat reduces mammary tumorigenesis in her offspring by means of changing the morphology of the mammary gland, the pattern of expression of specific genes and/or immune functions. PMID:9231913

  2. Retrospective comparison of abdominal ultrasonography and radiography in the investigation of feline abdominal disease

    PubMed Central

    Won, Wylen Wade; Sharma, Ajay; Wu, Wenbo

    2015-01-01

    Abdominal radiography and ultrasonography are commonly used as part of the initial diagnostic plan for cats with nonspecific signs of abdominal disease. This retrospective study compared the clinical usefulness of abdominal radiography and ultrasonography in 105 feline patients with signs of abdominal disease. The final diagnosis was determined more commonly with ultrasonography (59%) compared to radiography (25.7%). Ultrasonography was also able to provide additional clinically relevant information in 76% of cases, and changed or refined the diagnosis in 47% of cases. Based on these findings, ultrasonography may be sufficient as an initial diagnostic test for the investigation of feline abdominal disease. PMID:26483582

  3. Teaching of clinical ultrasonography to undergraduates: students as mentors.

    PubMed

    García de Casasola Sánchez, G; González Peinado, D; Sánchez Gollarte, A; Muñoz Aceituno, E; Peña Vázquez, I; Torres Macho, J

    2015-05-01

    Ultrasonography is a highly useful diagnostic technique that supplements traditional physical examinations. To demonstrate that students previously trained in clinical ultrasonography are capable of instructing other students in a similar manner in a short period of time ("peer mentoring"). Five medical students in their 5th year, trained in abdominal and cardiac ultrasonography by physicians with experience, instructed 24 other students in the same procedure. The training consisted of an online theoretical course and practical training lasting about 12hours, in which each student had to perform 6 basic abdominal planes and 4 basic cardiac planes on 20 healthy volunteers. Subsequently, the students underwent an objective assessment test on healthy models performed by expert physicians in clinical ultrasonography. The students managed to correctly identify 90.2% of the basic abdominal planes, except for the left coronal (spleen and left kidney) and subcostal (gallbladder) planes, with slightly lower success rates of 82.5% and 80%, respectively. Due to the greater difficulty of obtaining cardiac planes, the success rate was lower: 70.3%, in the subxiphoid, short parasternal and four chamber planes. The cardiac plane with the fewest errors in identification was the parasternal long plane (90% success). We observed no statistically significant differences between the results (teaching capacity) of the various mentors. Medical students are capable of instructing other colleagues (peer mentoring) on the basic aspects of abdominal and cardiac ultrasonography after a relatively short training period. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  4. DNA Methylation Status of the Estrogen Receptor α Gene in Canine Mammary Tumors.

    PubMed

    Brandão, Yara de Oliveira; Toledo, Mariana Busato; Chequin, Andressa; Cristo, Thierry Grima; Sousa, Renato Silva; Ramos, Edneia Amancio Souza; Klassen, Giseli

    2018-01-01

    Estrogen receptor α (ERα) has an important role in mammary carcinogenesis, prognosis, and treatment. In human and canine mammary cancer, the most aggressive tumors show loss of ERα expression, which in human breast cancer has been attributed to methylation of the cytosine followed by guanine (CpG) island within the estrogen receptor α gene ( ESR1) promoter. This study aimed to investigate the role of ESR1 CpG island (CGI) methylation in ERα expression in canine mammary tumors. Twenty-one canine mammary samples were sorted into three groups: malignant tumor (n = 9), benign tumor (n = 8), and normal gland (n = 4). Immunohistochemical analysis and reverse-transcription quantitative real-time PCR were performed to assess ERα expression and ESR1 mRNA levels. The methylation status was determined using sodium-bisulfite-treated DNA sequencing. All normal mammary glands and benign tumors showed high ERα expression (score range, 5-8). Six of the nine malignant tumors did not show ERα expression (score 0), two had score 2, and one had score 4. Lower ERα ( P < .005) and ESR1 mRNA levels ( P < .005) were found in malignant mammary tumors than in the other two groups. Canine ESR1 has an intragenic and non-promoter-associated CGI, different from humans. No significant variation in methylation percentage was observed among the groups, suggesting that ESR1 is not regulated by DNA methylation, unlike that in humans. This difference should be considered in further research using ERα as a biomarker for mammary tumors in canine studies on ERα-targeting therapy.

  5. Early detection, aggressive therapy: optimizing the management of feline mammary masses.

    PubMed

    Giménez, Fernanda; Hecht, Silke; Craig, Linden E; Legendre, Alfred M

    2010-03-01

    This article reviews the incidence, etiology, diagnosis, treatment and prognosis of mammary tumors in cats. Approximately 80% of feline mammary masses are malignant, with adenocarcinoma being the most common tumor type. Early diagnosis is, therefore, essential to improve the prognosis and quality of life of affected cats. Surgery is the most widely used treatment for malignant tumors. However, as mammary tumors are often advanced and metastasis has already occurred by the time of diagnosis, surgery routinely does not provide a cure. Ovariohysterectomy or hormonal therapy are the treatments of choice for fibroadenomatous hyperplasia (the most common benign mass) and usually lead to a successful outcome. Copyright 2010. Published by Elsevier Ltd.

  6. Linear array ultrasonography to stage rectal neoplasias suitable for local treatment.

    PubMed

    Ravizza, Davide; Tamayo, Darina; Fiori, Giancarla; Trovato, Cristina; De Roberto, Giuseppe; de Leone, Annalisa; Crosta, Cristiano

    2011-08-01

    Because of the many therapeutic options available, a reliable staging is crucial for rectal neoplasia management. Adenomas and cancers limited to the submucosa without lymph node involvement may be treated locally. The aim of this study is to evaluate the diagnostic accuracy of endorectal ultrasonography in the staging of neoplasias suitable for local treatment. We considered all patients who underwent endorectal ultrasonography between 2001 and 2010. The study population consisted of 92 patients with 92 neoplasias (68 adenocarcinomas and 24 adenomas). A 5 and 7.5MHz linear array echoendoscope was used. The postoperative histopathologic result was compared with the preoperative staging defined by endorectal ultrasonography. Adenomas and cancers limited to the submucosa were considered together (pT0-1). The sensitivity, specificity, overall accuracy rate, positive predictive value, and negative predictive value of endorectal ultrasonography for pT0-1 were 86%, 95.6%, 91.3%, 94.9% and 88.7%. Those for nodal involvement were 45.4%, 95.5%, 83%, 76.9% and 84%, with 3 false positive results and 12 false negative. For combined pT0-1 and pN0, endorectal ultrasonography showed an 87.5% sensitivity, 95.9% specificity, 92% overall accuracy rate, 94.9% positive predictive value and 90.2% negative predictive value. Endorectal linear array ultrasonography is a reliable tool to detect rectal neoplasias suitable for local treatment. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  7. Changes in ultrasonography indicators of abnormally invasive placenta during pregnancy.

    PubMed

    Calì, Giuseppe; Timor-Trisch, Ilan E; Palacios-Jaraquemada, Josè; Monteaugudo, Ana; Forlani, Francesco; Minneci, Gabriella; Foti, Francesca; Buca, Danilo; Familiari, Alessandra; Scambia, Giovanni; Liberati, Marco; D'Antonio, Francesco

    2018-03-01

    To ascertain whether the prevalence of ultrasonography signs of abnormally invasive placenta (AIP) changes during pregnancy. The present retrospective analysis included women with a prenatal diagnosis of AIP that was confirmed at delivery between January 1, 2007, and April 30, 2017, at the Department of Obstetrics and Gynaecology, Arnas Civico Hospital, Palermo, Italy. Ultrasonography signs of AIP were recorded at four different intervals during pregnancy: early first (6-9 weeks), first (11-14 weeks), second (15-24 weeks), and third trimester (25-36 weeks). There were 105 pregnancies included. Low implantation of the gestational sac was present on all ultrasonography images from the early first trimester compared with on 23 of 83 (27.7%) images from 11-14 weeks of pregnancy. The identification of loss of the clear space, placental lacunae, bladder wall interruption, and uterovesical hypervascularity all increased (all P<0.001) from the early first trimester onwards; these could all be identified in a majority of patients at 11-14 weeks of pregnancy. The prevalence of ultrasonography signs suggestive of AIP varied throughout pregnancy. During the early first trimester, indicators of AIP were similar to those of a cesarean scar pregnancy; classical ultrasonography signs of AIP were already present at 11-14 weeks of pregnancy for most patients. © 2017 International Federation of Gynecology and Obstetrics.

  8. Polythelia pilosa: a particular form of accessory mammary tissue.

    PubMed

    Camacho, F; González-Cámpora, R

    1998-01-01

    The old Kajawa classification which considered eight possible forms of aberrant mammary tissue has been recently modified into a simpler one that considers this condition only when there is glandular parenchyma or when the aberrant tissue is not a glandular tissue but a nipple, an areola or both. This new classification disregards 'polythelia pilosa' defined as an 'isolated patch of hairs only'. To demonstrate that polythelia pilosa is at least a marker of subjacent accessory mammary tissue and, consequently, that the term should be incorporated into the current classification. Among 72 cases of aberrant or accessory mammary tissue, we have studied 14 cases (7 men and 7 women) that were clinically diagnosed as 'visible isolated patches of hairs, apparently without pigmentation nor structures of areola or nipple'. We excised such isolated patches in 3 women. The histopathological examination showed an acanthotic and hyperpigmented epithelium with central depression closed by keratin plugs; in the dermis there were follicles with hairs surrounded by hypertrophic sebaceous glands. In the deepest portion, abundant secretory glomerules and excretory ducts of apocrine gland type could be observed. Since the biopsy of isolated patches of hairs demonstrated structures of either areolar or apocrine glandular tissue, we think that the term 'polythelia pilosa' should be reinstated into the classification as it is at least a marker of true aberrant mammary structures in men and hirsute women.

  9. The Efficacy of Thoracic Ultrasonography in Postoperative Newborn Patients after Cardiac Surgery

    PubMed Central

    Ozturk, Erkut; Tanidir, Ibrahim Cansaran; Yildiz, Okan; Ergul, Yakup; Guzeltas, Alper

    2017-01-01

    Objective In this study, the efficacy of thoracic ultrasonography during echocardiography was evaluated in newborns. Methods Sixty newborns who had undergone pediatric cardiac surgery were successively evaluated between March 1, 2015, and September 1, 2015. Patients were evaluated for effusion, pulmonary atelectasis, and pneumothorax by ultrasonography, and results were compared with X-ray findings. Results Sixty percent (n=42) of the cases were male, the median age was 14 days (2-30 days), and the median body weight was 3.3 kg (2.8-4.5 kg). The median RACHS-1 score was 4 (2-6). Atelectasis was demonstrated in 66% (n=40) of the cases. Five of them were determined solely by X-ray, 10 of them only by ultrasonography, and 25 of them by both ultrasonography and X-ray. Pneumothorax was determined in 20% (n=12) of the cases. Excluding one case determined by both methods, all of the 11 cases were diagnosed by X-ray. Pleural effusion was diagnosed in 26% (n=16) of the cases. Four of the cases were demonstrated solely by ultrasonography, three of them solely by X-ray, and nine of the cases by both methods. Pericardial effusion was demonstrated in 10% (n=6) of the cases. Except for one of the cases determined by both methods, five of the cases were diagnosed by ultrasonography. There was a moderate correlation when all pathologies evaluated together (k=0.51). Conclusion Thoracic ultrasonography might be a beneficial non-invasive method to evaluate postoperative respiratory problems in newborns who had congenital cardiac surgery. PMID:28977200

  10. Atypical chemokine receptor ACKR2 controls branching morphogenesis in the developing mammary gland

    PubMed Central

    Hewit, Kay D.; Pallas, Kenneth J.; Cairney, Claire J.; Lee, Kit M.; Hansell, Christopher A.; Stein, Torsten

    2017-01-01

    Macrophages are important regulators of branching morphogenesis during development and postnatally in the mammary gland. Regulation of macrophage dynamics during these processes can therefore have a profound impact on development. We demonstrate here that the developing mammary gland expresses high levels of inflammatory CC-chemokines, which are essential in vivo regulators of macrophage migration. We further demonstrate that the atypical chemokine receptor ACKR2, which scavenges inflammatory CC-chemokines, is differentially expressed during mammary gland development. We have previously shown that ACKR2 regulates macrophage dynamics during lymphatic vessel development. Here, we extend these observations to reveal a novel role for ACKR2 in regulating the postnatal development of the mammary gland. Specifically, we show that Ackr2−/− mice display precocious mammary gland development. This is associated with increased macrophage recruitment to the developing gland and increased density of the ductal epithelial network. These data demonstrate that ACKR2 is an important regulator of branching morphogenesis in diverse biological contexts and provide the first evidence of a role for chemokines and their receptors in postnatal development processes. PMID:27888192

  11. Sasa health exerts a protective effect on Her2/NeuN mammary tumorigenesis.

    PubMed

    Ren, Mingqiang; Reilly, R Todd; Sacchi, Nicoletta

    2004-01-01

    Bamboo grass leaves of different Sasa species have been widely used in food and medicine in Eastern Asia for hundreds of years. Of special interest are Kumazasa (Sasa senanensis rehder) leaves used to prepare an alkaline extract known as Sasa Health. This extract was reported to inhibit both the development and growth of mammary tumors in a mammary tumor strain of virgin SHN mice (1). We found that Sasa Health exerts a significant protective effect on spontaneous mammary tumorigenesis in another mouse model of human breast cancer, the transgenic FVB-Her2/NeuN mouse model. Two cohorts of Her2/NeuN female mice of different age (eleven-week-old and twenty-four-week-old) chronically treated with Sasa Health in drinking water showed both a delay in the development of tumors and reduced tumor multiplicity. Sasa Health also induced inhibition of mammary duct branching and side bud development in association with reduced angiogenesis. Altogether these findings indicate that Sasa Health contains phytochemicals that can effectively retard spontaneous mammary tumorigenesis.

  12. The Mammary Stem Cell Hierarchy: A Looking Glass into Heterogeneous Breast Cancer Landscapes

    PubMed Central

    Sreekumar, Amulya; Roarty, Kevin; Rosen, Jeffrey M.

    2015-01-01

    The mammary gland is a dynamic organ that undergoes extensive morphogenesis during the different stages of embryonic development, puberty, estrus, pregnancy, lactation and involution. Systemic and local cues underlie this constant tissue remodeling and act by eliciting an intricate pattern of responses in the mammary epithelial and stromal cells. Decades of studies utilizing methods such as transplantation and lineage tracing have identified a complex hierarchy of mammary stem cells, progenitors and differentiated epithelial cells that fuel mammary epithelial development. Importantly, these studies have extended our understanding of the molecular crosstalk between cell types, and signaling pathways maintaining normal homeostasis that often are deregulated during tumorigenesis. While several questions remain, this research has many implications for breast cancer. Fundamental among these are the identification of the cells of origin for the multiple subtypes of breast cancer and the understanding of tumor heterogeneity. A deeper understanding of these critical questions will unveil novel breast cancer drug targets and treatment paradigms. In this review, we provide a current overview of normal mammary development and tumorigenesis from a stem cell perspective. PMID:26206777

  13. Morphological and immunohistochemical characterization of spontaneous mammary tumours in European hedgehogs (Erinaceus europaeus).

    PubMed

    Döpke, C; Fehr, M; Thiele, A; Pohlenz, J; Wohlsein, P

    2007-07-01

    Mammary tumour samples (11 surgical and five post-mortem) from 16 adult European hedgehogs submitted between 1980 and 2004 were examined. Histologically, the tumours were classified as simple tubulo-papillary carcinomas with local invasive growth. In six cases, tumour cell emboli were present in blood vessels or lymphatic vessels, or both. However, metastasis to regional lymph nodes was found only in one hedgehog. Malignant neoplastic epithelial cells were immunolabelled by antibodies specific for various cytokeratins (CKs), including CK1-8, 10, 13-16, 19 and 20. CK expression did not differ from that in normal mammary gland tissue. CK20 was expressed in the mammary tissue of hedgehogs, in contrast to that of dogs and cats; CK7 immunolabelling, however, which commonly occurs in mammary epithelial cells, was negative. CK20 expression, together with the lack of CK7 as determined by a protein-specific antibody, represented an important difference from the CK profile shown by mammary epithelial cells of other mammalian species, including the dog and cat.

  14. Oxytocin binding sites in bovine mammary tissue

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhao, Xin.

    1989-01-01

    Oxytocin binding sites were identified and characterized in bovine mammary tissue. ({sup 3}H)-oxytocin binding reached equilibrium by 50 min at 20{degree}C and by 8 hr at 4{degree}C. The half-time of displacement at 20{degree}C was approximately 1 hr. Thyrotropin releasing hormone, adrenocorticotropin, angiotensin I, angiotensin II, pentagastrin, bradykinin, xenopsin and L-valyl-histidyl-L-leucyl-L-threonyl-L-prolyl-L-valyl-L-glutamyl-L-lysine were not competitive. In the presence of 10 nM LiCl, addition of oxytocin to dispersed bovine mammary cells, in which phosphatidylinositol was pre-labelled, caused a time and dose-dependent increase in radioactive inositiol monophosphate incorporation. The possibility that there are distinct vasopressin receptors in bovine mammary tissue was investigated. ({sup 3}H)-vasopressinmore » binding reached equilibrium by 40 min at 20{degree}. The half-time of displacement at 20{degree}C was approximately 1 hr. The ability of the peptides to inhibit ({sup 3}H)-vasopressin binding was: (Thr{sup 4},Gly{sup 7})-oxytocin > Arg{sup 8}-vasopressin > (lys{sup 8})-vasopressin > (Deamino{sup 1},D-arg{sup 8})-vasopressin > oxytocin > d (CH{sub 2}){sub 5}Tyr(Me)AVP.« less

  15. Induction of a Pregnancy-Like Mammary Gland Differentiation by Docosapentaenoic Omega-3 Fatty Acid

    DTIC Science & Technology

    2008-09-01

    xylenes, and stored in methyl salicylate . Morphological Assessment of Mammary Gland—Whole inguinal mammary glands were removed from virgin control as...respectively, defatted in xylenes, and stored in methyl salicylate . Quantitative RT-PCR analyses RNA was isolated and subjected to real time PCR analysis... methylation , and fatty acid analysis were performed as previously described [28,48]. Briefly, an ali- quot of mammary tissue homogenate in a glass

  16. Screening ultrasonography of 2,204 patients with blunt abdominal trauma in the Wenchuan earthquake.

    PubMed

    Zhou, Jixiang; Huang, Jiwei; Wu, Hong; Jiang, Hui; Zhang, Heqing; Prasoon, Pankaj; Xu, Yinglong; Bai, Yannan; Qiu, Jianguo; Zeng, Yong

    2012-10-01

    Abdominal injuries constitute a small proportion of all earthquake-related traumas; however, it often resulted in fatal hemorrhage. Ultrasonography has been described as an effective triage tool in the evaluation of blunt abdominal trauma. We aimed to present an overview of the diagnostic accuracy of screening ultrasonography for patients with blunt abdominal trauma admitted to various hospitals during the Wenchuan earthquake in China. We retrospectively analyzed the patients with blunt abdominal trauma who underwent ultrasonography after admission to various hospitals. Ultrasonography findings were considered positive if evidence of free fluid or a parenchymal injury was identified. Ultrasonography findings were compared with the findings of computed tomography, diagnostic peritoneal lavage, repeated ultrasonography, cystography, operation, and/or the clinical course. Findings from 2,204 ultrasonographic examinations were evaluated. Findings of 199 ultrasonographic examinations (9.0%) were considered positive. Of the patients, 12 (0.5%) had a false-negative ultrasonographic findings; of this group, 3 (25%) required exploratory laparotomy. Ultrasonography had a sensitivity of 91.9%, specificity of 96.9%, and an accuracy of 96.6% for detection of abdominal injuries. Positive predictive value was 68.3%, and negative predictive value was 99.4%. Screening ultrasonography is highly reliable in the setting of blunt abdominal trauma after earthquake. It should be used as an initial diagnostic modality in the evaluation of most blunt abdominal trauma. Diagnostic study, level III.

  17. Effects of Chronic Genistein Treatment in Mammary Gland, Uterus, and Vagina

    PubMed Central

    Rimoldi, Guillermo; Christoffel, Julie; Seidlova-Wuttke, Dana; Jarry, Hubertus; Wuttke, Wolfgang

    2007-01-01

    Background The isoflavone genistein (GEN) is found in soy (Glycine max) and red clover (Trifolium pratense). The estrogenic activity of GEN is known, and it is widely advertised as a phytoestrogen useful in alleviating climacteric complaints and other postmenopausal disorders. Knowledge of effects of long-term administration of GEN in laboratory animals is scarce, and effects in the uterus and mammary gland after long-term administration have not been studied. The uterus and mammary gland are known to be negatively influenced by estrogens used in hormone therapy. Objectives We administered two doses of GEN [mean daily uptake 5.4 (low) or 54 mg/kg (high) body weight (bw)] orally over a period of 3 months to ovariectomized (ovx) rats and compared the effects with a treatment with two doses of 17β-estradiol [E2; 0.17 (low) or 0.7 mg/kg bw (high)]. Mammary glands, vaginae, and uteri were investigated morphologically and immunohistochemically. We quantified the expression of proliferating cell nuclear antigen (PCNA) and progesterone receptor (PR) in the mammary gland. Results In rats treated with either of the E2 doses or the high GEN dose, we found increased uterine weight, and histologic analysis showed estrogen-induced features in the uteri. In vaginae, either E2 dose or GEN high induced hyperplastic epithelium compared with the atrophic controls. In the mammary gland, E2 (either dose) or GEN increased proliferation and PR expression. Serum levels of luteinizing hormone were decreased by E2 (both doses) but not by GEN. Conclusions In summary, E2 and GEN share many effects in the studied organs, particularly in the vagina, uterus, and mammary gland but not in the hypothalamo/pituitary unit. PMID:18174952

  18. Adipose and mammary epithelial tissue engineering.

    PubMed

    Zhu, Wenting; Nelson, Celeste M

    2013-01-01

    Breast reconstruction is a type of surgery for women who have had a mastectomy, and involves using autologous tissue or prosthetic material to construct a natural-looking breast. Adipose tissue is the major contributor to the volume of the breast, whereas epithelial cells comprise the functional unit of the mammary gland. Adipose-derived stem cells (ASCs) can differentiate into both adipocytes and epithelial cells and can be acquired from autologous sources. ASCs are therefore an attractive candidate for clinical applications to repair or regenerate the breast. Here we review the current state of adipose tissue engineering methods, including the biomaterials used for adipose tissue engineering and the application of these techniques for mammary epithelial tissue engineering. Adipose tissue engineering combined with microfabrication approaches to engineer the epithelium represents a promising avenue to replicate the native structure of the breast.

  19. Adipose and mammary epithelial tissue engineering

    PubMed Central

    Zhu, Wenting; Nelson, Celeste M.

    2013-01-01

    Breast reconstruction is a type of surgery for women who have had a mastectomy, and involves using autologous tissue or prosthetic material to construct a natural-looking breast. Adipose tissue is the major contributor to the volume of the breast, whereas epithelial cells comprise the functional unit of the mammary gland. Adipose-derived stem cells (ASCs) can differentiate into both adipocytes and epithelial cells and can be acquired from autologous sources. ASCs are therefore an attractive candidate for clinical applications to repair or regenerate the breast. Here we review the current state of adipose tissue engineering methods, including the biomaterials used for adipose tissue engineering and the application of these techniques for mammary epithelial tissue engineering. Adipose tissue engineering combined with microfabrication approaches to engineer the epithelium represents a promising avenue to replicate the native structure of the breast. PMID:23628872

  20. Mammary molecular portraits reveal lineage-specific features and progenitor cell vulnerabilities.

    PubMed

    Casey, Alison E; Sinha, Ankit; Singhania, Rajat; Livingstone, Julie; Waterhouse, Paul; Tharmapalan, Pirashaanthy; Cruickshank, Jennifer; Shehata, Mona; Drysdale, Erik; Fang, Hui; Kim, Hyeyeon; Isserlin, Ruth; Bailey, Swneke; Medina, Tiago; Deblois, Genevieve; Shiah, Yu-Jia; Barsyte-Lovejoy, Dalia; Hofer, Stefan; Bader, Gary; Lupien, Mathieu; Arrowsmith, Cheryl; Knapp, Stefan; De Carvalho, Daniel; Berman, Hal; Boutros, Paul C; Kislinger, Thomas; Khokha, Rama

    2018-06-19

    The mammary epithelium depends on specific lineages and their stem and progenitor function to accommodate hormone-triggered physiological demands in the adult female. Perturbations of these lineages underpin breast cancer risk, yet our understanding of normal mammary cell composition is incomplete. Here, we build a multimodal resource for the adult gland through comprehensive profiling of primary cell epigenomes, transcriptomes, and proteomes. We define systems-level relationships between chromatin-DNA-RNA-protein states, identify lineage-specific DNA methylation of transcription factor binding sites, and pinpoint proteins underlying progesterone responsiveness. Comparative proteomics of estrogen and progesterone receptor-positive and -negative cell populations, extensive target validation, and drug testing lead to discovery of stem and progenitor cell vulnerabilities. Top epigenetic drugs exert cytostatic effects; prevent adult mammary cell expansion, clonogenicity, and mammopoiesis; and deplete stem cell frequency. Select drugs also abrogate human breast progenitor cell activity in normal and high-risk patient samples. This integrative computational and functional study provides fundamental insight into mammary lineage and stem cell biology. © 2018 Casey et al.

  1. Basic fibroblast growth factor in an animal model of spontaneous mammary tumor progression.

    PubMed

    Kao, Steven; Mo, Jeffrey; Baird, Andrew; Eliceiri, Brian P

    2012-06-01

    Although basic fibroblast growth factor (FGF2) was the first pro-angiogenic molecule discovered, it has numerous activities on the growth and differentiation of non-vascular cell types. FGF2 is both stimulatory and inhibitory, depending on the cell type evaluated, the experimental design used and the context in which it is tested. Here, we investigated the effects of manipulating endogenous FGF2 on the development of mammary cancer to determine whether its endogenous contribution in vivo is pro- or anti-tumorigenic. Specifically, we examined the effects of FGF2 gene dosing in a cross between a spontaneous breast tumor model (PyVT+ mice) and FGF2-/- (FGF KO) mice. Using these mice, the onset and progression of mammary tumors was determined. As predicted, female FGF2 WT mice developed mammary tumors starting around 60 days after birth and by 80 days, 100% of FGF2 WT female mice had mammary tumors. In contrast, 80% of FGF2 KO female mice had no palpable tumors until nearly three weeks later (85 days) at times when 100% of the WT cohort was tumor positive. All FGF KO mice were tumor-bearing by 115 days. When we compared the onset of mammary tumor development and the tumor progression curves between FGF het and FGF KO mice, we observed a difference, which suggested a gene dosing effect. Analysis of the tumors demonstrated that there were significant differences in tumor size depending on FGF2 status. The delay in tumor onset supports a functional role for FGF2 in mammary tumor progression, but argues against an essential role for FGF2 in overall mammary tumor progression.

  2. Lgr4 regulates mammary gland development and stem cell activity through the pluripotency transcription factor Sox2.

    PubMed

    Wang, Ying; Dong, Jie; Li, Dali; Lai, Li; Siwko, Stefan; Li, Yi; Liu, Mingyao

    2013-09-01

    The key signaling networks regulating mammary stem cells are poorly defined. The leucine-rich repeat containing G protein-coupled receptor (Lgr) family has been implicated in intestinal, gastric, and epidermal stem cell functions. We investigated whether Lgr4 functions in mammary gland development and mammary stem cells. We found that Lgr4(-/-) mice had delayed ductal development, fewer terminal end buds, and decreased side-branching. Crucially, the mammary stem cell repopulation capacity was severely impaired. Mammospheres from Lgr4(-/-) mice showed decreased Wnt signaling. Wnt3a treatment prevented the adverse effects of Lgr4 loss on organoid formation. Chromatin immunoprecipitation analysis indicated that Sox2 expression was controlled by the Lgr4/Wnt/β-catenin/Lef1 pathway. Importantly, Sox2 overexpression restored the in vivo mammary regeneration potential of Lgr4(-/-) mammary stem cells. Therefore, Lgr4 activates Sox2 to regulate mammary development and stem cell functions via Wnt/β-catenin/Lef1. © AlphaMed Press.

  3. Synergistic effects of androgen and estrogen on the mouse uterus and mammary gland.

    PubMed

    Zhang, Jian; Sun, Yibin; Liu, Yunhai; Sun, Yi; Liao, Dezhong Joshua

    2004-10-01

    Many studies have suggested that elevated estrogens and androgens may be etiologically related to the development of breast cancer, endometrial cancer and uterine leiomyomas. We and other investigators have previously shown that estrogen and androgen are synergistic in the induction of mammary carcinogenesis in the Noble rat. However, the mechanisms behind the synergy is unknown, and it is unclear whether such synergy is unique for the Noble rat and for the mammary gland. In this study we treated female FVB mice with 17beta-estradiol (E2) and 5alpha-dihydrotestosterone-bezonate (DHT-B), alone and in combination, using silastic tubing for 2-7 months. The results showed that DHT-B alone induced proliferation of uterine endometrial epithelium and myometrial smooth muscle cells, whereas E2 alone induced much more pronounced growth of endometrial epithelium without affecting smooth muscle cells. Combined treatment with E2+DHT-B caused an even more severe hyperplasia of endometrial epithelium and myometrial muscle cells, compared with the treatment with each hormone alone. Uterine leiomyomas were observed in 2 of 6 mice at 7 months of combined treatment but not in any of 6 or 7 mice receiving each single hormone. DHT-B alone induced growth and secretion of mammary ductal cells, as well as growth of mammary stroma. E2 alone stimulated much more pronounced growth of both ductal cells and alveolar cells and secretion of alveolar cells, but had no effect on mammary stroma. Treatment with both E2 and DHT-B caused more severe hyperplasia of mammary ducts and alveoli, compared to the treatment with each hormone alone. Intraductal hyperplasia occurred early and frequently in the E2+DHT-B- treated mice, but no mammary tumors were observed. These results suggest that E2 and DHT-B have synergistic effects on the growth of uterine endometrial epithelium and myometrial muscle cells, as well as mammary epithelial ducts and alveoli.

  4. Physical Confirmation and Comparative Genomics of the Rat Mammary carcinoma susceptibility 3 Quantitative Trait Locus.

    PubMed

    Le, Saasha; Martin, Zachary C; Samuelson, David J

    2017-06-07

    Human breast and rat mammary cancer susceptibility are complex phenotypes where complete sets of risk associated loci remain to be identified for both species. We tested multiple congenic rat strains to physically confirm and positionally map rat Mammary carcinoma susceptibility 3 ( Mcs3 )-a mammary cancer resistance allele previously predicted at Rattus norvegicus chromosome 1 ( RNO1 ). The mammary cancer susceptible Wistar Furth (WF) strain was the recipient, and the mammary cancer resistant Copenhagen (Cop) strain was the RNO1 -segment donor for congenics. Inbred WF females averaged 6.3 carcinogen-induced mammary carcinomas per rat. Two WF.Cop congenic strains averaged 2.8 and 3.4 mammary carcinomas per rat, which confirmed Mcs3 as an independently acting allele. Two other WF.Cop congenic strains averaged 6.6 and 8.1 mammary carcinomas per rat, and, thus, did not contain Mcs3 Rat Mcs3 was delimited to 27.8 Mb of RNO1 from rs8149408 to rs105131702 ( RNO1 :143700228-171517317 of RGSC 6.0/rn6). Human genetic variants with p values for association to breast cancer risk below 10 -7 had not been reported for Mcs3 orthologous loci; however, human variants located in Mcs3 -orthologous regions with potential association to risk (10 -7  <  p  < 10 -3 ) were listed in some population-based studies. Further, rat Mcs3 contains sequence orthologous to human 11q13/14 -a region frequently amplified in female breast cancer. We conclude that Mcs3 is an independently acting mammary carcinoma resistance allele. Human population-based, genome-targeted association studies interrogating Mcs3 orthologous loci may yield novel breast cancer risk associated variants and genes. Copyright © 2017 Le et al.

  5. The diagnosis of neonatal pulmonary atelectasis using lung ultrasonography.

    PubMed

    Liu, Jing; Chen, Shui-Wen; Liu, Fang; Li, Qiu-Ping; Kong, Xiang-Yong; Feng, Zhi-Chun

    2015-04-01

    Ultrasonography has been used for the diagnosis of many kinds of lung conditions, but few studies have investigated ultrasound for the diagnosis of neonatal pulmonary atelectasis (NAP). In this study, we evaluated the usefulness of lung ultrasonography for the diagnosis of NPA. From May 2012 to December 2013, 80 neonates with NPA and 50 neonates without lung disease were enrolled in this study. Each lung of every infant was divided into the anterior, lateral, and posterior regions by the anterior and posterior axillary lines. Each region was scanned carefully with the probe perpendicular or parallel to the ribs. The ultrasound findings were confirmed by chest radiograph (CXR) or CT scan. Sixty of the 80 patients with signs of NPA on lung ultrasound also had signs of NPA on CXR (termed focal-type atelectasis), and the other 20 patients had signs of NPA on chest CT scan while there were no abnormal findings on CXR (termed occult lung atelectasis). In patients with NPA, the main ultrasound findings were large areas of lung consolidation with clearly demarcated borders, air bronchograms, pleural line abnormalities, and absence of A-lines, as well as the presence of lung pulse and absence of lung sliding on real-time ultrasound. The sensitivity of lung ultrasonography for the diagnosis of NPA was 100%, whereas the sensitivity of CXR was 75%. Large areas of lung consolidation with clearly demarcated borders were only observed in patients with NPA. Lung ultrasonography is an accurate and reliable method for diagnosing NPA; most importantly, it can find those occult lung atelectasis that could not be detected on CXR. Routine lung ultrasonography is a useful method of diagnosing or excluding NPA in neonates.

  6. Mammary stem cells: Novel markers and novel approaches to increase lactation efficiency

    USDA-ARS?s Scientific Manuscript database

    Mammary stem cells (MaSC) provide for net growth, renewal and turnover of mammary epithelial cells, and are therefore potential targets for strategies to increase production efficiency. Appropriate regulation of MaSC can potentially benefit milk yield, persistency, dry period management and tissue r...

  7. Un(MaSC)ing Stem Cell Dynamics in Mammary Branching Morphogenesis.

    PubMed

    Greenwood, Erin; Wrenn, Emma D; Cheung, Kevin J

    2017-02-27

    The properties of stem cells that participate in mammary gland branching morphogenesis remain contested. Reporting in Nature, Scheele et al. (2017) establish a model for post-pubertal mammary branching morphogenesis in which position-dependent, lineage-restricted stem cells undergo cell mixing in order to contribute to long-term growth. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Canonical Wnt Signaling as a Specific Marker of Normal and Tumorigenic Mammary Stem Cells

    DTIC Science & Technology

    2010-02-01

    for mammary stem cells and be a target for transformation that results in the formation of aggressive mammary tumors. Breast cancer stem cells, Wnt...tumorigenesis, and human breast cancer. In addition, increasing evidence suggests that tumors arise from either normal stem or progenitor cells...population of mammary tumor cells that are CD24+/CD49++. Since Wnt pathway activation occurs in human breast cancer and is required for

  9. Investigating the Role of FIP200 in Mammary Carcinogenesis Using a Transgenic Mouse Model

    DTIC Science & Technology

    2007-04-01

    analysis of virgin and lactating female mice in which FAK was specifically deleted in the mammary epithelium. No morphological abnormalities were found in...the mammary gland of virgin mice however, lactating mice have severe lobulo-alveolar hypoplasia in the mammary gland. After completing the analysis...were collected to prepare protein extracts. Organs were first snap-frozen in liquid nitrogen and then were ground using a mortar and a pestle

  10. Metabolic Alterations in Mammary Cancer Prevention by Withaferin A in a Clinically Relevant Mouse Model

    PubMed Central

    2013-01-01

    Background Efficacy of withaferin A (WA), an Ayurvedic medicine constituent, for prevention of mammary cancer and its associated mechanisms were investigated using mouse mammary tumor virus–neu (MMTV-neu) transgenic model. Methods Incidence and burden of mammary cancer and pulmonary metastasis were scored in female MMTV-neu mice after 28 weeks of intraperitoneal administration with 100 µg WA (three times/week) (n = 32) or vehicle (n = 29). Mechanisms underlying mammary cancer prevention by WA were investigated by determination of tumor cell proliferation, apoptosis, metabolomics, and proteomics using plasma and/or tumor tissues. Spectrophotometric assays were performed to determine activities of complex III and complex IV. All statistical tests were two-sided. Results WA administration resulted in a statistically significant decrease in macroscopic mammary tumor size, microscopic mammary tumor area, and the incidence of pulmonary metastasis. For example, the mean area of invasive cancer was lower by 95.14% in the WA treatment group compared with the control group (mean = 3.10 vs 63.77mm2, respectively; difference = –60.67mm2; 95% confidence interval = –122.50 to 1.13mm2; P = .0536). Mammary cancer prevention by WA treatment was associated with increased apoptosis, inhibition of complex III activity, and reduced levels of glycolysis intermediates. Proteomics confirmed downregulation of many glycolysis-related proteins in the tumor of WA-treated mice compared with control, including M2-type pyruvate kinase, phospho glycerate kinase, and fructose-bisphosphate aldolase A isoform 2. Conclusions This study reveals suppression of glycolysis in WA-mediated mammary cancer prevention in a clinically relevant mouse model. PMID:23821767

  11. [Clinical results of double versus single mammary artery myocardiac revascularization: 15 years of follow-up].

    PubMed

    López Rodríguez, F J; Voces, R; Lima, P; Reyes, G; Silva, J; Ruiz, M; Rico, M; González De Diego, F; Fortuny, R; Garrido, G; González Santos, J M; Albertos, J; Fernández Calella, D; Vallejo, J L

    2001-07-01

    Use of the left internal mammary artery to bypass the left anterior descending coronary artery reduces cardiac events and increases survival. However, there is some controversy as to the benefits of using both mammary arteries. To assess the long-term outcome of the use of both mammary arteries in comparison with the use of only one. A retrospective cohort study with a mean follow-up of 9.0 +/- 4.2 years was performed including 108 patients consecutively revascularized using both mammary arteries (II) and 108 patients randomly chosen in whom one mammary artery (I) was used for this purpose. Both groups were similar. There were no differences between the groups in operative morbidity or mortality. The survival at 10 years was similar (II: 84.61 +/- 4%; I: 85.18 +/- 3.8%), whereas recurrence of angina (II: 29.63 +/- 5.3%; I: 47.55 +/- 5.6%) (p = 0.012), the requirement for percutaneous angioplasty (II: 3.98 +/- 2%; I: 12.99 +/- 4.1%) (p = 0.009) and cardiologic events (II: 33.48 +/- 5.5%; I: 48.48 +/- 5.5%)(p = 0.022) were all lower in the group in which both mammary arteries were used. In the multivariate analysis, the use of both mammary arteries was an independent protective factor against angina recurrence (RR = 0.55), angioplasty (RR = 0.18) and cardiologic event (RR = 0.60). The use of both mammary arteries for revascularization does not increase operative morbidity. Since this procedure acts as an independent factor against angina recurrence, angioplasty and cardiologic event

  12. Diagnostic utility of abdominal ultrasonography in dogs with chronic vomiting.

    PubMed

    Leib, M S; Larson, M M; Panciera, D L; Troy, G C; Monroe, W E; Rossmeisl, J H; Forrester, S D; Herring, E S

    2010-01-01

    Chronic vomiting is a common problem in dogs that has many causes. Ultrasonographic descriptions of many gastrointestinal (GI) diseases have been published. However, diagnostic utility of ultrasonography in dogs with chronic vomiting has not been investigated. Diagnostic utility of abdominal ultrasound will be highest in dogs with GI neoplasia and lowest in those with inflammatory disorders. Eighty-nine pet dogs with chronic vomiting. Medical records were reviewed and the contribution of abdominal ultrasound to the clinical diagnosis was subjectively scored. In 68.5% of dogs, the reviewers thought that the same diagnosis would have been reached without performing ultrasonography. In 22.5% of dogs, the ultrasound examination was considered to be vital or beneficial to the diagnosis. Univariable analysis identified that increased diagnostic utility was associated with increasing age, a greater number of vomiting episodes per week, presence of weight loss, a greater percentage of lost body weight, and a final diagnosis of GI lymphoma or gastric adenocarcinoma. However, multivariate analysis only identified increasing age and a final diagnosis of gastric adenocarcinoma or GI lymphoma to be associated with increased diagnostic utility. In 12.4% of dogs, additional benefits of ultrasonography to case management, excluding the contribution to the vomiting problem, were identified. The diagnostic utility of abdominal ultrasonography was high in 27% of dogs. The presence of factors that are associated with high diagnostic utility is an indication to perform abdominal ultrasonography in dogs with chronic vomiting.

  13. Regulation of gene expression in human mammary epithelium: effect of breast pumping

    USDA-ARS?s Scientific Manuscript database

    Little is known of the molecular regulation of human milk production because of limitations in obtaining mammary tissue from lactating women. Our objectives were to evaluate whether RNA isolated from breast milk fat globules (MFGs) could be an alternative to mammary biopsies and to determine whether...

  14. [Degradation of prolactin 125-I in the mammary gland of lactating rats].

    PubMed

    Marinchenko, G V; Taranenko, A G

    1977-01-01

    Prolactin-125I metabolism in the mammary gland of lactating rats was studied; the hormone was injected intraperitoneally. Radioactive products accumulated by the mammary gland tissue were extracted with isotonic medium. Tissue extracts, blood serum and milk were analyzed by gel filtration on Sephadex G-200. The Blood displayed a gradual reduction of prolactin-125I content as a result of its splitting in the organs and binding with blood proteins; as to the mammary gland--there occurred accumulation of the products of prolactin-125I degradation. Some hormone was inactivated losing immunological properties without any significant changes in the molecular weight. Besides, the mammary gland displayed an intensive accumulation of the products of prolactin-125I splitting in the other organs and in the gland proper. Radioactivity accumulated in the milk was mainly referred to the products of prolactin-125I degradation. There was also shown the presence of immunologically active prolactin-125I in the milk.

  15. Principles of treatment for mammary gland tumors.

    PubMed

    Novosad, C Andrew

    2003-05-01

    The mammary glands are frequent locations for the development of tumors. In the dog and cat, early detection and rapid therapy are necessary to prevent both local and distant metastasis. In the dog, this disease can have a range of biologic behaviors, whereas in the cat it is almost always an extremely aggressive disease. Treatment options depend on tumor staging and can include surgery, radiation therapy, chemotherapy, or a combination. As we become better at early diagnosis and are able to implement aggressive therapy, we are becoming more and more successful in the treatment of this disease. In the following article, we will discuss current thoughts surrounding the diagnosis and treatment options for both canine and feline mammary gland tumors.

  16. An economic evaluation of second-trimester genetic ultrasonography for prenatal detection of down syndrome.

    PubMed

    Vintzileos, A M; Ananth, C V; Fisher, A J; Smulian, J C; Day-Salvatore, D; Beazoglou, T; Knuppel, R A

    1998-11-01

    The objective of this study was to perform an economic evaluation of second-trimester genetic ultrasonography for prenatal detection of Down syndrome. More specifically, we sought to determine the following: (1) the diagnostic accuracy requirements (from the cost-benefit point of view) of genetic ultrasonography versus genetic amniocentesis for women at increased risk for fetal Down syndrome and (2) the possible economic impact of second-trimester genetic ultrasonography for the US population on the basis of the ultrasonographic accuracies reported in previously published studies. A cost-benefit equation was developed from the hypothesis that the cost of universal genetic amniocentesis of patients at increased risk for carrying a fetus with Down syndrome should be at least equal to the cost of universal genetic ultrasonography with amniocentesis used only for those with abnormal ultrasonographic results. The main components of the equation included the diagnostic accuracy of genetic ultrasonography (sensitivity and specificity for detecting Down syndrome), the costs of the amniocentesis package and genetic ultrasonography, and the lifetime cost of Down syndrome cases not detected by the genetic ultrasonography. After appropriate manipulation of the equation a graph was constructed, representing the balance between sensitivity and false-positive rate of genetic ultrasonography; this was used to examine the accuracy of previously published studies from the cost-benefit point of view. Sensitivity analyses included individual risks for Down syndrome ranging from 1:261 (risk of a 35-year-old at 18 weeks' gestation) to 1:44 (risk of a 44-year-old at 18 weeks' gestation). This economic evaluation was conducted from the societal perspective. Genetic ultrasonography was found to be economically beneficial only if the overall sensitivity for detecting Down syndrome was >74%. Even then, the cost-benefit ratio depended on the corresponding false-positive rate. Of the 7

  17. The transcriptome of estrogen-independent mammary growth reveals that not all mammary glands are created equally

    USDA-ARS?s Scientific Manuscript database

    Allometric growth of ducts in the mammary glands (MG) is widely-held to be estrogen (E)-dependent. We previously discovered that the dietary fatty acid trans-10, cis-12 conjugated linoleic acid (CLA) stimulates E-independent allometric growth and TEB formation in ovariectomized mice. Given the simil...

  18. Imaging of juvenile spondyloarthritis. Part II: Ultrasonography and magnetic resonance imaging

    PubMed Central

    Znajdek, Michał; Gietka, Piotr; Vasilevska-Nikodinovska, Violeta; Patrovic, Lukas; Salapura, Vladka

    2017-01-01

    Juvenile spondyloarthropathies are mainly manifested by symptoms of peripheral arthritis and enthesitis. Early involvement of sacroiliac joints and spine is exceptionally rare in children; this usually happens in adulthood. Conventional radiographs visualize late inflammatory lesions. Early diagnosis is possible with the use of ultrasonography and magnetic resonance imaging. The first part of the article presented classifications and radiographic presentation of juvenile spondyloarthropathies. This part discusses changes seen on ultrasonography and magnetic resonance imaging. In patients with juvenile spondyloarthropathies, these examinations are conducted to diagnose inflammatory lesions in peripheral joints, tendon sheaths, tendons and bursae. Moreover, magnetic resonance also shows subchondral bone marrow edema, which is considered an early sign of inflammation. Ultrasonography and magnetic resonance imaging do not show specific lesions for any rheumatic disease. Nevertheless, they are conducted for early diagnosis, treatment monitoring and identifying complications. This article presents a spectrum of inflammatory changes and discusses the diagnostic value of ultrasonography and magnetic resonance imaging. PMID:29075522

  19. Selective expression of neuropeptides in the rat mammary gland: somatostatin gene is expressed during lactation.

    PubMed

    Chen, A; Laskar-Levy, O; Koch, Y

    1999-12-01

    The existence of numerous neuropeptides in milk, in concentrations that exceed those in maternal plasma, is well established. It is still unclear whether these neuropeptides are produced by the mammary gland or that the gland concentrates them from the general circulation. In this study, we have examined the possibility that the genes of these neuropeptides are expressed in the rat mammary gland. RNA was extracted from the mammary glands of female rats during different stages of reproduction as well as from other tissues such as hypothalami, pancreas, pineal glands, small intestine, and ovaries. Following RT reaction, the resulting cDNA were amplified by radioactive PCR using specific oligonucleotide primers. We have used specific primers for the following neuropeptides: galanin, somatostatin, vasoactive intestinal peptide, TRH, GH-releasing hormone, cholecystokinin, neurotensin, oxytocin, and relaxin. We have also used primers for serotonin N-acetyl-transferase, the enzyme that is involved in melatonin biosynthesis. The ribosomal protein S-16 served as an internal control. Among all the neuropeptides that have been examined, somatostatin was the only one that was found to be expressed in the mammary gland. Somatostatin was expressed in the mammary gland of lactating rats, but not of virgin rats. Expression of the somatostatin gene was confirmed by Southern blot analysis and by sequencing of the PCR products. Immunohistochemical studies demonstrated somatostatin immunoreactivity in the epithelial cells that compose the secretory alveoli and in the secretory material. In addition, we have found that the mammary glands of the lactating rat express the PC-1 proteinase gene that process prosomatostatin to generate somatostatin-14, but do not express furin, the enzyme that is responsible for somatostatin-28 production. This finding substantiates previous studies that demonstrated that only somatostatin-14 is present in milk. The finding that most of the neuropeptides

  20. Endocrine hormones and local signals during the development of the mouse mammary gland.

    PubMed

    Brisken, Cathrin; Ataca, Dalya

    2015-01-01

    Most of mammary gland development occurs postnatally under the control of female reproductive hormones, which in turn interact with other endocrine factors. While hormones impinge on many tissues and trigger very complex biological responses, tissue recombination experiments with hormone receptor-deficient mammary epithelia revealed eminent roles for estrogens, progesterone, and prolactin receptor (PrlR) signaling that are intrinsic to the mammary epithelium. A subset of the luminal mammary epithelial cells expresses the estrogen receptor α (ERα), the progesterone receptor (PR), and the PrlR and act as sensor cells. These cells convert the detected systemic signals into local signals that are developmental stage-dependent and may be direct, juxtacrine, or paracrine. This setup ensures that the original input is amplified and that the biological responses of multiple cell types can be coordinated. Some key mediators of hormone action have been identified such as Wnt, EGFR, IGFR, and RANK signaling. Multiple signaling pathways such as FGF, Hedgehog, and Notch signaling participate in driving different aspects of mammary gland development locally but how they link to the hormonal control remains to be elucidated. An increasing number of endocrine factors are appearing to have a role in mammary gland development, the adipose tissue is increasingly recognized to play a role in endocrine regulation, and a complex role of the immune system with multiple different cell types is being revealed. For further resources related to this article, please visit the WIREs website. © 2015 Wiley Periodicals, Inc.

  1. Apples prevent mammary tumors in rats.

    PubMed

    Liu, Rui Hai; Liu, Jiaren; Chen, Bingqing

    2005-03-23

    Regular consumption of fruits and vegetables has been consistently shown to be associated with reduced risk of developing chronic diseases such as cancer and cardiovascular disease. Apples are commonly consumed and are the major contributors of phytochemicals in human diets. It was previously reported that apple extracts exhibit strong antioxidant and antiproliferative activities and that the major part of total antioxidant activity is from the combination of phytochemicals. Phytochemicals, including phenolics and flavonoids, are suggested to be the bioactive compounds contributing to the health benefits of apples. Here it is shown that whole apple extracts prevent mammary cancer in a rat model in a dose-dependent manner at doses comparable to human consumption of one, three, and six apples a day. This study demonstrated that whole apple extracts effectively inhibited mammary cancer growth in the rat model; thus, consumption of apples may be an effective strategy for cancer protection.

  2. Social isolation induces autophagy in the mouse mammary gland: link to increased mammary cancer risk

    PubMed Central

    Sumis, Allison; Cook, Katherine L; Andrade, Fabia O; Hu, Rong; Kidney, Emma; Zhang, Xiyuan; Kim, Dominic; Carney, Elissa; Nguyen, Nguyen; Yu, Wei; Bouker, Kerrie B; Cruz, Idalia; Clarke, Robert; Hilakivi-Clarke, Leena

    2018-01-01

    Social isolation is a strong predictor of early all-cause mortality and consistently increases breast cancer risk in both women and animal models. Because social isolation increases body weight, we compared its effects to those caused by a consumption of obesity-inducing diet (OID) in C57BL/6 mice. Social isolation and OID impaired insulin and glucose sensitivity. In socially isolated, OID-fed mice (I-OID), insulin resistance was linked to reduced Pparg expression and increased neuropeptide Y levels, but in group-housed OID fed mice (G-OID), it was linked to increased leptin and reduced adiponectin levels, indicating that the pathways leading to insulin resistance are different. Carcinogen-induced mammary tumorigenesis was significantly higher in I-OID mice than in the other groups, but cancer risk was also increased in socially isolated, control diet-fed mice (I-C) and G-OID mice compared with that in controls. Unfolded protein response (UPR) signaling (GRP78; IRE1) was upregulated in the mammary glands of OID-fed mice, but not in control diet-fed, socially isolated I-C mice. In contrast, expression of BECLIN1, ATG7 and LC3II were increased, and p62 was downregulated by social isolation, indicating increased autophagy. In the mammary glands of socially isolated mice, but not in G-OID mice, mRNA expressions of p53 and the p53-regulated autophagy inducer Dram1 were upregulated, and nuclear p53 staining was strong. Our findings further indicated that autophagy and tumorigenesis were not increased in Atg7+/− mice kept in social isolation and fed OID. Thus, social isolation may increase breast cancer risk by inducing autophagy, independent of changes in body weight. PMID:27550962

  3. Social isolation induces autophagy in the mouse mammary gland: link to increased mammary cancer risk.

    PubMed

    Sumis, Allison; Cook, Katherine L; Andrade, Fabia O; Hu, Rong; Kidney, Emma; Zhang, Xiyuan; Kim, Dominic; Carney, Elissa; Nguyen, Nguyen; Yu, Wei; Bouker, Kerrie B; Cruz, Idalia; Clarke, Robert; Hilakivi-Clarke, Leena

    2016-10-01

    Social isolation is a strong predictor of early all-cause mortality and consistently increases breast cancer risk in both women and animal models. Because social isolation increases body weight, we compared its effects to those caused by a consumption of obesity-inducing diet (OID) in C57BL/6 mice. Social isolation and OID impaired insulin and glucose sensitivity. In socially isolated, OID-fed mice (I-OID), insulin resistance was linked to reduced Pparg expression and increased neuropeptide Y levels, but in group-housed OID fed mice (G-OID), it was linked to increased leptin and reduced adiponectin levels, indicating that the pathways leading to insulin resistance are different. Carcinogen-induced mammary tumorigenesis was significantly higher in I-OID mice than in the other groups, but cancer risk was also increased in socially isolated, control diet-fed mice (I-C) and G-OID mice compared with that in controls. Unfolded protein response (UPR) signaling (GRP78; IRE1) was upregulated in the mammary glands of OID-fed mice, but not in control diet-fed, socially isolated I-C mice. In contrast, expression of BECLIN1, ATG7 and LC3II were increased, and p62 was downregulated by social isolation, indicating increased autophagy. In the mammary glands of socially isolated mice, but not in G-OID mice, mRNA expressions of p53 and the p53-regulated autophagy inducer Dram1 were upregulated, and nuclear p53 staining was strong. Our findings further indicated that autophagy and tumorigenesis were not increased in Atg7(+/-) mice kept in social isolation and fed OID. Thus, social isolation may increase breast cancer risk by inducing autophagy, independent of changes in body weight. © 2016 Society for Endocrinology.

  4. Ultrasonography evaluation during the weaning process: the heart, the diaphragm, the pleura and the lung.

    PubMed

    Mayo, P; Volpicelli, G; Lerolle, N; Schreiber, A; Doelken, P; Vieillard-Baron, A

    2016-07-01

    On a regular basis, the intensivist encounters the patient who is difficult to wean from mechanical ventilatory support. The causes for failure to wean from mechanical ventilatory support are often multifactorial and involve a complex interplay between cardiac and pulmonary dysfunction. A potential application of point of care ultrasonography relates to its utility in the process of weaning the patient from mechanical ventilatory support. This article reviews some applications of ultrasonography that may be relevant to the process of weaning from mechanical ventilatory support. The authors have divided these applications of ultrasonography into four separate categories: the assessment of cardiac, diaphragmatic, and lung function; and the identification of pleural effusion; which can all be evaluated with ultrasonography during a dynamic process in which the intensivist is uniquely positioned to use ultrasonography at the point of care. Ultrasonography may have useful application during the weaning process from mechanical ventilatory support.

  5. Shear-wave elastography in breast ultrasonography: the state of the art

    PubMed Central

    2017-01-01

    Shear-wave elastography (SWE) is a recently developed ultrasound technique that can visualize and measure tissue elasticity. In breast ultrasonography, SWE has been shown to be useful for differentiating benign breast lesions from malignant breast lesions, and it has been suggested that SWE enhances the diagnostic performance of ultrasonography, potentially improving the specificity of conventional ultrasonography using the Breast Imaging Reporting and Data System criteria. More recently, not only has SWE been proven useful for the diagnosis of breast cancer, but has also been shown to provide valuable information that can be used as a preoperative predictor of the prognosis or response to chemotherapy. PMID:28513127

  6. [Pathomorphosis of the mammary gland tissue during radical interventions using high-frequency electrosurgical welding].

    PubMed

    Bondar', G V; Sedakov, I E; Kobets, R A

    2011-04-01

    High-frequency electric welding of a live soft tissues (HFEW LST) is applied widely in all surgical specialties. Its application in surgery of mammary gland cancer constitutes a perspective trend. The impact of HFEW LST and monopolar electrocoagulation on tissues while performing radical operations in patients-women for mammary gland cancer was studied up. Basing on analysis of pathomorphological investigations data, the possibility and perspective of the welding technologies application, while performing radical operations on mammary glands, were established.

  7. Sequestration of human cytomegalovirus by human renal and mammary epithelial cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Twite, Nicolas; Andrei, Graciela; Kummert, Caroline

    2014-07-15

    Urine and breast milk represent the main routes of human cytomegalovirus (HCMV) transmission but the contribution of renal and mammary epithelial cells to viral excretion remains unclear. We observed that kidney and mammary epithelial cells were permissive to HCMV infection and expressed immediate early, early and late antigens within 72 h of infection. During the first 24 h after infection, high titers of infectious virus were measured associated to the cells and in culture supernatants, independently of de novo synthesis of virus progeny. This phenomenon was not observed in HCMV-infected fibroblasts and suggested the sequestration and the release of HCMVmore » by epithelial cells. This hypothesis was supported by confocal and electron microscopy analyses. The sequestration and progressive release of HCMV by kidney and mammary epithelial cells may play an important role in the excretion of the virus in urine and breast milk and may thereby contribute to HCMV transmission. - Highlights: • Primary renal and mammary epithelial cells are permissive to HCMV infection. • HCMV is sequestered by epithelial cells and this phenomenon does not require viral replication. • HCMV sequestration by epithelial cells is reduced by antibodies and IFN-γ.« less

  8. Role of ultrasonography in detecting mammographically occult breast carcinoma in women with dense breasts.

    PubMed

    Corsetti, V; Ferrari, A; Ghirardi, M; Bergonzini, R; Bellarosa, S; Angelini, O; Bani, C; Ciatto, S

    2006-04-01

    The purpose of this study was to assess the usefulness of routine ultrasonography in women with negative mammography and dense breasts [Breast Imaging Reporting and Data System (BIRADS D3-4)]. We applied a protocol involving routine ultrasonography in a consecutive series of subjects with negative mammography and dense breasts. After evaluation by internal and external reviewers of cancers detected by ultrasonography performed to confirm negative mammography, we determined the additional cancer detection rate of ultrasonography and the cost of the protocol. Out of 17,883 total mammographies, 167 cancers were diagnosed (detection rate: 0.93%). Out of 257 suspicious mammographies, 138 cancers were detected. Out of 17,626 negative mammographies, 6,449 (36.5%) were classified as "dense breast" and underwent ultrasonography: 29 cancers were detected (detection rate: 0.44%, or 17.3% of total cancers). Out of 25 cancer cases reviewed, negative mammography and asymptomatic status was confirmed in 15 (detection rate 0.23%, or 8.9% of total cancers). The cancer detection rate was 0.11%, 0.22%, 0.32% and 0.14% for age groups <40, 40-49, 50-59 and >59, respectively. The cost per additional carcinoma detected by ultrasonography alone was euro 25,847.85 whereas that per examined woman was euro 21.68. The study confirms the possibility that ultrasonography can detect mammographically occult breast carcinoma in dense breasts. The evidence is insufficient to recommend this policy in routine screening practice but suggests that, at least in current clinical practice, adding ultrasonography in dense breasts may be useful despite the substantial costs.

  9. Tammar wallaby mammary cathelicidins are differentially expressed during lactation and exhibit antimicrobial and cell proliferative activity.

    PubMed

    Wanyonyi, Stephen S; Sharp, Julie A; Khalil, Elie; Lefevre, Christophe; Nicholas, Kevin R

    2011-11-01

    Cathelicidins secreted in milk may be central to autocrine feedback in the mammary gland for optimal development in addition to conferring innate immunity to both the mammary gland and the neonate. This study exploits the unique reproductive strategy of the tammar wallaby (Macropus eugenii) model to analyse differential splicing of cathelicidin genes and to evaluate the bactericidal activity and effect of the protein on mammary epithelial cell proliferation. Two linear peptides, Con73 and Con218, derived from the heterogeneous carboxyl end of cathelicidin transcripts, MaeuCath1 and MaeuCath7 respectively, were evaluated for antimicrobial activity. Both Con73 and Con218 significantly inhibited the growth of Staphylococcus aureus, Pseudomonas aureginosa, Enterococcus faecalis and Salmonella enterica. In addition both MaeuCath1 and MaeuCath7 stimulated proliferation of primary tammar wallaby mammary epithelial cells (WallMEC). Lactation-phase specific alternate spliced transcripts were determined for MaeuCath1 showing utilisation of both antimicrobial and proliferative functions are required by the mammary gland and the suckled young. The study has shown for the first time that temporal regulation of milk cathelicidins may be crucial in antimicrobial protection of the mammary gland and suckled young and mammary cell proliferation. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Advanced Imaging Approaches to Characterize Stromal and Metabolic Changes in In Vivo Mammary Tumor Models

    DTIC Science & Technology

    2013-03-01

    characterization and toward future intravital studies. Preliminary fluorescence lifetime images were also collected intravitally through a mammary imaging window...intend to use this characterization to understand shifts in fluorescence lifetime collected by intravital imaging using a mammary imaging window...collected intravitally through a mammary imaging window implanted in a female, PyVT positive, Col1a1 heterozygote, mouse (Figure 7). A paper has

  11. Characterization of immortalized human mammary epithelial cell line HMEC 2.6.

    PubMed

    Joshi, Pooja S; Modur, Vishnu; Cheng, JiMing; Robinson, Kathy; Rao, Krishna

    2017-10-01

    Primary human mammary epithelial cells have a limited life span which makes it difficult to study them in vitro for most purposes. To overcome this problem, we have developed a cell line that was immortalized using defined genetic elements, and we have characterized this immortalized non-tumorigenic human mammary epithelial cell line to establish it as a potential model system. human mammary epithelial cells were obtained from a healthy individual undergoing reduction mammoplasty at SIU School of Medicine. The cells were transduced with CDK4R24C followed by transduction with human telomerase reverse transcriptase. Post all manipulation, the cells displayed a normal cell cycle phase distribution and were near diploid in nature, which was confirmed by flow cytometry and karyotyping. In vitro studies showed that the cells were anchorage dependent and were non-invasive in nature. The cell line expressed basal epithelial markers such as cytokeratin 7, CD10, and p63 and was negative for the expression of estrogen receptor and progesterone receptor. Upon G-band karyotyping, the cell line displayed the presence of a few cytogenic abnormalities, including trisomy 20 and trisomy 7, which are also commonly present in other immortalized mammary cell lines. Furthermore, the benign nature of these cells was confirmed by multiple in vitro and in vivo experiments. Therefore, we think that this cell line could serve as a good model to understand the molecular mechanisms involved in the development and progression of breast cancer and to also assess the effect of novel therapeutics on human mammary epithelial cells.

  12. Varying Susceptibility of the Female Mammary Gland to In Utero Windows of BPA Exposure.

    PubMed

    Hindman, Andrea R; Mo, Xiaokui Molly; Helber, Hannah L; Kovalchin, Claire E; Ravichandran, Nanditha; Murphy, Alina R; Fagan, Abigail M; St John, Pamela M; Burd, Craig J

    2017-10-01

    In utero exposure to the endocrine disrupting compound bisphenol A (BPA) is known to disrupt mammary gland development and increase tumor susceptibility in rodents. It is unclear whether different periods of in utero development might be more susceptible to BPA exposure. We exposed pregnant CD-1 mice to BPA at different times during gestation that correspond to specific milestones of in utero mammary gland development. The mammary glands of early-life and adult female mice, exposed in utero to BPA, were morphologically and molecularly (estrogen receptor-α and Ki67) evaluated for developmental abnormalities. We found that BPA treatment occurring before mammary bud invasion into the mesenchyme [embryonic day (E)12.5] incompletely resulted in the measured phenotypes of mammary gland defects. Exposing mice up to the point at which the epithelium extends into the precursor fat pad (E16.5) resulted in a nearly complete BPA phenotype and exposure during epithelial extension (E15.5 to E18.5) resulted in a partial phenotype. Furthermore, the relative differences in phenotypes between exposure windows highlight the substantial correlations between early-life molecular changes (estrogen receptor-α and Ki67) in the stroma and the epithelial elongation defects in mammary development. These data further implicate BPA action in the stroma as a critical mediator of epithelial phenotypes. Copyright © 2017 Endocrine Society.

  13. Trans-Fatty Acid-Stimulated Mammary Gland Growth in Ovariectomized Mice is Fatty Acid Type and Isomer Specific.

    PubMed

    Berryhill, Grace E; Miszewski, Susan G; Trott, Josephine F; Kraft, Jana; Lock, Adam L; Hovey, Russell C

    2017-03-01

    We previously reported that the trans-18:2 fatty acid trans-10, cis-12 conjugated linoleic acid (t10,c12-CLA) stimulates mammary gland development independent of estrogen and its receptor. Given the negative consequences of dietary trans-fatty acids on various aspects of human health, we sought to establish whether other trans-fatty acids could similarly induce ovary-independent mammary gland growth in mice. Prepubertal BALB/cJ mice were ovariectomized at 21 days of age then were fed diets enriched with cis-9, trans-11 CLA (c9,t11-CLA), or mixtures of trans-18:1 fatty acids supplied by partially hydrogenated sunflower, safflower, or linseed oil. The resultant mammary phenotype was evaluated 3 weeks later and compared to the growth response elicited by t10,c12-CLA, or the defined control diet. Whereas partially hydrogenated safflower oil increased mammary gland weight, none of the partially hydrogenated vegetable oils promoted mammary ductal growth. Similarly, the c9,t11-CLA supplemented diet was without effect on mammary development. Taken together, our data emphasize a unique effect of t10,c12-CLA in stimulating estrogen-independent mammary gland growth manifest as increased mammary ductal area and elongation that was not recapitulated by c9,t11-CLA or the partially hydrogenated vegetable oil diets.

  14. EMMPRIN (basigin/CD147) expression is not correlated with MMP activity during adult mouse mammary gland development.

    PubMed

    Szymanowska, Malgorzata; Hendry, Kay A K; Robinson, Claire; Kolb, Andreas F

    2009-01-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN/basigin/CD147) is a cell surface protein, which has been associated with the induction of matrix metalloproteinase (MMP) genes during cancer metastasis. EMMPRIN plays a role in a variety of physiological processes as is evident by the diverse deficiencies detectable in EMMPRIN knockout mice. We have analysed the role of EMMPRIN in the induction of MMP genes during mammary gland differentiation and involution. Co-transfection studies showed that EMMPRIN has diverse effects on MMP promoter activity in different mammary and non-mammary cell lines. Expression of EMMPRIN mRNA is enhanced markedly by insulin in a mammary gland cell line but appears to have no direct effect on MMP gene expression in these cells. Microarray analysis and quantitative PCR show that EMMPRIN is expressed throughout mammary gland differentiation in the mouse. Its expression decreases during early pregnancy and briefly after induction of mammary gland involution by litter removal. Immunohistochemical analysis shows that EMMPRIN expression is limited to the stromal compartment during pregnancy, whereas it is strongly expressed in the epithelium during lactation. In summary the data argue against a causal role for EMMPRIN for the induction of MMP gene expression during adult mammary gland development. These data therefore support a physiological role for EMMPRIN other than MMP induction in mammary gland biology. 2008 Wiley-Liss, Inc.

  15. CLOCK regulates mammary epithelial cell growth and differentiation

    PubMed Central

    Crodian, Jennifer; Suárez-Trujillo, Aridany; Erickson, Emily; Weldon, Bethany; Crow, Kristi; Cummings, Shelby; Chen, Yulu; Shamay, Avi; Mabjeesh, Sameer J.; Plaut, Karen

    2016-01-01

    Circadian clocks influence virtually all physiological processes, including lactation. Here, we investigate the role of the CLOCK gene in regulation of mammary epithelial cell growth and differentiation. Comparison of mammary morphology in late-pregnant wild-type and ClockΔ19 mice, showed that gland development was negatively impacted by genetic loss of a functional timing system. To understand whether these effects were due, in part, to loss of CLOCK function in the gland, the mouse mammary epithelial cell line, HC11, was transfected with short hairpin RNA that targeted Clock (shClock). Cells transfected with shClock expressed 70% less Clock mRNA than wild-type (WT) HC11 cultures, which resulted in significantly depressed levels of CLOCK protein (P < 0.05). HC11 lines carrying shClock had four-fold higher growth rates (P < 0.05), and the percentage of cells in G1 phase was significantly higher (90.1 ± 1.1% of shClock vs. 71.3 ± 3.6% of WT-HC11) following serum starvation. Quantitative-PCR (qPCR) analysis showed shClock had significant effects (P < 0.0001) on relative expression levels of Ccnd1, Wee1, and Tp63. qPCR analysis of the effect of shClock on Fasn and Cdh1 expression in undifferentiated cultures and cultures treated 96 h with dexamethasone, insulin, and prolactin (differentiated) found levels were reduced by twofold and threefold, respectively (P < 0.05), in shClock line relative to WT cultures. Abundance of CDH1 and TP63 proteins were significantly reduced in cultures transfected with shClock. These data support how CLOCK plays a role in regulation of epithelial cell growth and differentiation in the mammary gland. PMID:27707717

  16. Effects of the Insulin-like Growth Factor Pathway on the Regulation of Mammary Gland Development.

    PubMed

    Ha, Woo Tae; Jeong, Ha Yeon; Lee, Seung Yoon; Song, Hyuk

    2016-09-01

    The insulin-like growth factor (IGF) pathway is a key signal transduction pathway involved in cell proliferation, migration, and apoptosis. In dairy cows, IGF family proteins and binding receptors, including their intracellular binding partners, regulate mammary gland development. IGFs and IGF receptor interactions in mammary glands influence the early stages of mammogenesis, i.e., mammary ductal genesis until puberty. The IGF pathway includes three major components, IGFs (such as IGF-I, IGF-II, and insulin), their specific receptors, and their high-affinity binding partners (IGF binding proteins [IGFBPs]; i.e., IGFBP1-6), including specific proteases for each IGFBP. Additionally, IGFs and IGFBP interactions are critical for the bioactivities of various intracellular mechanisms, including cell proliferation, migration, and apoptosis. Notably, the interactions between IGFs and IGFBPs in the IGF pathway have been difficult to characterize during specific stages of bovine mammary gland development. In this review, we aim to describe the role of the interaction between IGFs and IGFBPs in overall mammary gland development in dairy cows.

  17. The Role of Nuclear Receptor Coactivator A1B1 in Growth Factor-Mediated Mammary Tumorigenesis

    DTIC Science & Technology

    2007-03-01

    study display dwarfism and the retardation of mammary gland growth [9]. At the 4-month time point, I similarly observed an overall decrease in mammary...Coactivator A1B1 in Growth Factor- Mediated Mammary Tumorigenesis PRINCIPAL INVESTIGATOR: Mark P Fereshteh (BS) CONTRACTING ORGANIZATION...U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION

  18. Management of mastitis and abscessation of mammary glands secondary to fibroadenomatous hyperplasia in a primiparturient cat.

    PubMed

    Burstyn, Uri

    2010-02-01

    A 1-year-old sexually intact female domestic shorthair cat was evaluated because of an 8-week history of pronounced mammary gland hyperplasia that had progressed to mastitis and abscessation of the mammary glands since parturition 7 days earlier. The cat was anorectic, was febrile, and had signs of discomfort. Its kittens were weak and appeared to have difficulty nursing. Physical examination revealed pyrexia, mastitis with abscessation in the 6 caudal mammary glands, skin ulceration over the nipples, and areas of skin necrosis over the abscessed mammary glands. A CBC revealed nonregenerative anemia and leukocytosis with a left shift (2.160 x 10(9) band cells/L) and toxic changes. Mastitis and incipient septicemia were considered the most likely causes. The history of mammary gland hyperplasia since the second week of pregnancy suggested a diagnosis of fibroadenomatous hyperplasia that predisposed the cat to subsequent mastitis. Surgical drainage of the abscessed mammary glands, debridement of necrotic skin, and placement of a Penrose drain resulted in rapid improvement in clinical status. Broad-spectrum antimicrobial treatment (amoxicillin-clavulanic acid) was prescribed, and the cat was discharged from the hospital. Mastitis and fibroadenomatous mammary gland hyperplasia resolved rapidly afterward. Management of abscessed mammary glands through surgical drainage and drain placement is an option for treatment of cats with complications of fibroadenomatous hyperplasia. In the cat of this report, the treatment approach resulted in rapid resolution of mastitis, was less invasive than mastectomy, and avoided the potential complications of treatment with a progesterone-receptor antagonist.

  19. A simple ductal mammary papilloma in a male maned wolf (Chrysocyon brachyurus).

    PubMed

    Cassali, Geovanni D; Bertagnolli, Angélica C; Ferreira, Enio; Malta, Marcelo C C

    2009-01-01

    A 1-cm-diameter nodule was identified in the left inguinal mammary gland of a 9-year-old male maned wolf (Chrysocyon brachyurus). The mass was surgically excised and examined histologically. Microscopically, the neoplasm consisted of papillary proliferations of epithelial cells on well-defined fibrovascular stalks. A myoepithelial layer was located between the single layer of epithelial cells and the fibrovascular stalk. This histologic appearance was compatible with a diagnosis of simple ductal mammary papilloma. Immunohistochemical staining was positive for p63, cytokeratins AE1/AE3, and estrogen receptors. The clinical and histologic observations in the present case indicate that male maned wolves may develop mammary tumors that are similar to those observed in domestic dogs and humans.

  20. FOXA1 is an essential determinant of ERα expression and mammary ductal morphogenesis

    PubMed Central

    Bernardo, Gina M.; Lozada, Kristen L.; Miedler, John D.; Harburg, Gwyndolen; Hewitt, Sylvia C.; Mosley, Jonathan D.; Godwin, Andrew K.; Korach, Kenneth S.; Visvader, Jane E.; Kaestner, Klaus H.; Abdul-Karim, Fadi W.; Montano, Monica M.; Keri, Ruth A.

    2010-01-01

    FOXA1, estrogen receptor α (ERα) and GATA3 independently predict favorable outcome in breast cancer patients, and their expression correlates with a differentiated, luminal tumor subtype. As transcription factors, each functions in the morphogenesis of various organs, with ERα and GATA3 being established regulators of mammary gland development. Interdependency between these three factors in breast cancer and normal mammary development has been suggested, but the specific role for FOXA1 is not known. Herein, we report that Foxa1 deficiency causes a defect in hormone-induced mammary ductal invasion associated with a loss of terminal end bud formation and ERα expression. By contrast, Foxa1 null glands maintain GATA3 expression. Unlike ERα and GATA3 deficiency, Foxa1 null glands form milk-producing alveoli, indicating that the defect is restricted to expansion of the ductal epithelium, further emphasizing the novel role for FOXA1 in mammary morphogenesis. Using breast cancer cell lines, we also demonstrate that FOXA1 regulates ERα expression, but not GATA3. These data reveal that FOXA1 is necessary for hormonal responsiveness in the developing mammary gland and ERα-positive breast cancers, at least in part, through its control of ERα expression. PMID:20501593

  1. Inhibition of rat mammary microsomal oxidation of ethanol to acetaldehyde by plant polyphenols.

    PubMed

    Maciel, María Eugenia; Castro, José Alberto; Castro, Gerardo Daniel

    2011-07-01

    We previously reported that the microsomal fraction from rat mammary tissue is able to oxidize ethanol to acetaldehyde, a mutagenic-carcinogenic metabolite, depending on the presence of NADPH and oxygen but not inhibited by carbon monoxide or other cytochrome P450 inhibitors. The process was strongly inhibited by diphenyleneiodonium, a known inhibitor of NADPH oxidase, and by nordihydroguaiaretic acid, an inhibitor of lipoxygenases. This led us to suggest that both enzymes could be involved. With the purpose of identifying natural compounds present in food with the ability to decrease the production of acetaldehyde in mammary tissue, in the present studies, several plant polyphenols having inhibitory effects on lipoxygenases and of antioxidant nature were tested as potential inhibitors of the rat mammary tissue microsomal pathway of ethanol oxidation. We included in the present screening study 32 polyphenols having ready availability and that were also tested against the rat mammary tissue cytosolic metabolism of ethanol to acetaldehyde. Several polyphenols were also able to inhibit the microsomal ethanol oxidation at concentrations as low was 10-50 μM. The results of these screening experiments suggest the potential of several plant polyphenols to prevent in vivo production and accumulation of acetaldehyde in mammary tissue.

  2. Effects of glucose on lactose synthesis in mammary epithelial cells from dairy cow.

    PubMed

    Lin, Ye; Sun, Xiaoxu; Hou, Xiaoming; Qu, Bo; Gao, Xuejun; Li, Qingzhang

    2016-05-26

    Lactose, as the primary osmotic component in milk, is the major determinant of milk volume. Glucose is the primary precursor of lactose. However, the effect of glucose on lactose synthesis in dairy cow mammary glands and the mechanism governing this process are poorly understood. Here we showed that glucose has the ability to induce lactose synthesis in dairy cow mammary epithelial cells, as well as increase cell viability and proliferation. A concentration of 12 mM glucose was the optimum concentration to induce cell growth and lactose synthesis in cultured dairy cow mammary epithelial cells. In vitro, 12 mM glucose enhanced lactose content, along with the expression of genes involved in glucose transportation and the lactose biosynthesis pathway, including GLUT1, SLC35A2, SLC35B1, HK2, β4GalT-I, and AKT1. In addition, we found that AKT1 knockdown inhibited cell growth and lactose synthesis as well as expression of GLUT1, SLC35A2, SLC35B1, HK2, and β4GalT-I. Glucose induces cell growth and lactose synthesis in dairy cow mammary epithelial cells. Protein kinase B alpha acts as a regulator of metabolism in dairy cow mammary gland to mediate the effects of glucose on lactose synthesis.

  3. Ultrasonography and magnetic resonance imaging in the diagnosis of Morton's neuroma.

    PubMed

    Fazal, Muhammad Ali; Khan, Ishrat; Thomas, Cherian

    2012-01-01

    Magnetic resonance imaging (MRI) and ultrasonography are used widely for the diagnosis of Morton's neuroma. The aim of this study was to assess the accuracy of these two modalities as diagnostic tools in Morton's neuroma. Fifty feet of 47 consecutive patients (39 women and 8 men; mean age, 46 years; age range, 36-64 years) who presented between January 1, 2005, and June 30, 2008, were included in the study. Twenty-five feet were investigated with ultrasonography and 25 with MRI. Morton's neuroma was confirmed surgically and histologically in all of the patients. A Student unpaired t test was applied. Twenty-two MRIs were diagnostic (sensitivity, 88%). Three patients with negative MRI findings underwent ultrasonography and were found to have a neuroma smaller than 5 mm. Twenty-four ultrasound scans demonstrated the neuroma (sensitivity, 96%), with five neuromas being smaller than 5 mm. Ultrasonography has a slightly higher sensitivity in the diagnosis of Morton's neuroma, particularly of neuromas smaller than 5 mm, and should be the preferred imaging modality in suspected cases, and MRI should be reserved for cases with equivocal diagnosis.

  4. Comparison of Radiography and Ultrasonography for Diagnosis of Diaphragmatic Hernia in Bovines

    PubMed Central

    Athar, Hakim; Mohindroo, Jitender; Singh, Kiranjeet; Kumar, Ashwani; Raghunath, Mulinti

    2010-01-01

    The present study was conducted on 101 animals suffering from thoracoabdominal disorders; out of which twenty seven animals (twenty six buffaloes and one cow) were diagnosed with diaphragmatic hernia based on clinical signs, radiography, ultrasonography, and left flank laparorumenotomy. Radiography alone confirmed diaphragmatic hernia in 18 cases (66.67%) with a sac-like structure cranial to the diaphragm. In 15 animals the sac contained metallic densities while in three cases a sac-like structure with no metallic densities was present. Ultrasonography was helpful in confirming diaphragmatic hernia in 23 cases (85.18%) and ultrasonographically reticular motility was evident at the level of 4th/5th intercostal space in all the animals. B+M mode ultrasonography was used for the first time for diagnosis of diaphragmatic hernia in bovines and the results suggested that ultrasonography was a reliable diagnostic modality for diaphragmatic hernia in bovines. PMID:20445795

  5. Performance of physical examination versus ultrasonography to detect stenosis in haemodialysis arteriovenous fistula.

    PubMed

    Maldonado-Cárceles, Ana B; García-Medina, José; Torres-Cantero, Alberto M

    2017-01-18

    The overall purpose of this study is to compare the accuracy of physical examination (PE) versus ultrasonography (US) in people with arteriovenous fistula (AVF). This is a cross-sectional study with a total of 99 patients attended by the vascular radiology unit for AVF evaluation during January - March 2015. PE and ultrasonography were blinded performed by different radiologists. For complete and individual signs of PE, sensitivity, specificity, predictive positive (PPV) and negative (PNV) value, likelihood ratios (LR) and Cohen's κ value were measured. According to ultrasonography, the presence of stenosis was identified in 57 (58%) patients, and 61 (62%) by PE. The accuracy of PE for the diagnosis of AVF was sensitivity 82%, specificity 67%, PPV 77%, NPV 74%, LR 2.74 and 0.26. There was a moderate agreement beyond chance between PE and ultrasonography (κ = 0.5). PE has shown a moderate accuracy to detect stenosis. With non-ultrasonography availability Haemodialysis Units can get benefit to optimize VA survival and professionals should improve its basic skills.

  6. Microcalcifications in breast cancer: novel insights into the molecular mechanism and functional consequence of mammary mineralisation

    PubMed Central

    Cox, R F; Hernandez-Santana, A; Ramdass, S; McMahon, G; Harmey, J H; Morgan, M P

    2012-01-01

    Background: Mammographic microcalcifications represent one of the most reliable features of nonpalpable breast cancer yet remain largely unexplored and poorly understood. Methods: We report a novel model to investigate the in vitro mineralisation potential of a panel of mammary cell lines. Primary mammary tumours were produced by implanting tumourigenic cells into the mammary fat pads of female BALB/c mice. Results: Hydroxyapatite (HA) was deposited only by the tumourigenic cell lines, indicating mineralisation potential may be associated with cell phenotype in this in vitro model. We propose a mechanism for mammary mineralisation, which suggests that the balance between enhancers and inhibitors of physiological mineralisation are disrupted. Inhibition of alkaline phosphatase and phosphate transport prevented mineralisation, demonstrating that mineralisation is an active cell-mediated process. Hydroxyapatite was found to enhance in vitro tumour cell migration, while calcium oxalate had no effect, highlighting potential consequences of calcium deposition. In addition, HA was also deposited in primary mammary tumours produced by implanting the tumourigenic cells into the mammary fat pads of female BALB/c mice. Conclusion: This work indicates that formation of mammary HA is a cell-specific regulated process, which creates an osteomimetic niche potentially enhancing breast tumour progression. Our findings point to the cells mineralisation potential and the microenvironment regulating it, as a significant feature of breast tumour development. PMID:22233923

  7. Comparison of the diagnostic value of ultrasonography and standing radiography for pelvic-femoral disorders in horses.

    PubMed

    Geburek, Florian; Rötting, Anna K; Stadler, Peter M

    2009-04-01

    To assess agreement between ultrasonography (transcutaneous and transrectal) and standing radiography in horses with fractures in the pelvic region and disorders of the coxofemoral joint. Case series. Warmblood horses (n=23) and 2 ponies. Medical records (1999-2008) of equids with pelvic or coxofemoral disorders that had pelvic radiography and ultrasonography were retrieved and results of both techniques compared. Radiography and ultrasonography each identified equal numbers of fractures of the tuber coxa (n=4), ilial shaft (2), ischium (3), femoral neck (2), and osteoarthritis/osis of the coxofemoral joint (6). Fractures of the ilial wing (4) were only identified by ultrasonography not by standing radiography. Of 9 acetabular fractures, 3 were identified on radiographs only, 5 were identified with both modalities. One pubic fracture was identified using ultrasonography and radiography. One acetabular and 1 pubic fracture were only diagnosed on necropsy. We found reasonable agreement (73%; 24/33) between ultrasonography and standing radiography for diagnosis of pelvic-femoral disorders. Ultrasonography was more useful for ilial wing fractures and radiography for acetabular fractures. Ultrasonography is a rapid, safe imaging technique for detecting disorders of the pelvic region with a high diagnostic yield and is a preferred initial approach in horses with severe hindlimb lameness.

  8. Transcriptome difference and potential crosstalk between liver and mammary tissue in mid-lactation primiparous dairy cows.

    PubMed

    Bu, Dengpan; Bionaz, Massimo; Wang, Mengzhi; Nan, Xuemei; Ma, Lu; Wang, Jiaqi

    2017-01-01

    Liver and mammary gland are among the most important organs during lactation in dairy cows. With the purpose of understanding both the different and the complementary roles and the crosstalk of those two organs during lactation, a transcriptome analysis was performed on liver and mammary tissues of 10 primiparous dairy cows in mid-lactation. The analysis was performed using a 4×44K Bovine Agilent microarray chip. The transcriptome difference between the two tissues was analyzed using SAS JMP Genomics using ANOVA with a false discovery rate correction (FDR). The analysis uncovered >9,000 genes differentially expressed (DEG) between the two tissues with a FDR<0.001. The functional analysis of the DEG uncovered a larger metabolic (especially related to lipid) and inflammatory response capacity in liver compared with mammary tissue while the mammary tissue had a larger protein synthesis and secretion, proliferation/differentiation, signaling, and innate immune system capacity compared with the liver. A plethora of endogenous compounds, cytokines, and transcription factors were estimated to control the DEG between the two tissues. Compared with mammary tissue, the liver transcriptome appeared to be under control of a large array of ligand-dependent nuclear receptors and, among endogenous chemical, fatty acids and bacteria-derived compounds. Compared with liver, the transcriptome of the mammary tissue was potentially under control of a large number of growth factors and miRNA. The in silico crosstalk analysis between the two tissues revealed an overall large communication with a reciprocal control of lipid metabolism, innate immune system adaptation, and proliferation/differentiation. In summary the transcriptome analysis confirmed prior known differences between liver and mammary tissue, especially considering the indication of a larger metabolic activity in liver compared with the mammary tissue and the larger protein synthesis, communication, and proliferative

  9. Transcriptome difference and potential crosstalk between liver and mammary tissue in mid-lactation primiparous dairy cows

    PubMed Central

    Bu, Dengpan; Bionaz, Massimo; Wang, Mengzhi; Nan, Xuemei; Ma, Lu; Wang, Jiaqi

    2017-01-01

    Liver and mammary gland are among the most important organs during lactation in dairy cows. With the purpose of understanding both the different and the complementary roles and the crosstalk of those two organs during lactation, a transcriptome analysis was performed on liver and mammary tissues of 10 primiparous dairy cows in mid-lactation. The analysis was performed using a 4×44K Bovine Agilent microarray chip. The transcriptome difference between the two tissues was analyzed using SAS JMP Genomics using ANOVA with a false discovery rate correction (FDR). The analysis uncovered >9,000 genes differentially expressed (DEG) between the two tissues with a FDR<0.001. The functional analysis of the DEG uncovered a larger metabolic (especially related to lipid) and inflammatory response capacity in liver compared with mammary tissue while the mammary tissue had a larger protein synthesis and secretion, proliferation/differentiation, signaling, and innate immune system capacity compared with the liver. A plethora of endogenous compounds, cytokines, and transcription factors were estimated to control the DEG between the two tissues. Compared with mammary tissue, the liver transcriptome appeared to be under control of a large array of ligand-dependent nuclear receptors and, among endogenous chemical, fatty acids and bacteria-derived compounds. Compared with liver, the transcriptome of the mammary tissue was potentially under control of a large number of growth factors and miRNA. The in silico crosstalk analysis between the two tissues revealed an overall large communication with a reciprocal control of lipid metabolism, innate immune system adaptation, and proliferation/differentiation. In summary the transcriptome analysis confirmed prior known differences between liver and mammary tissue, especially considering the indication of a larger metabolic activity in liver compared with the mammary tissue and the larger protein synthesis, communication, and proliferative

  10. Cystic Mammary Adenocarcinoma Associated with a Prolactin-secreting Pituitary Adenoma in a New Zealand White Rabbit (Oryctolagus cuniculus)

    PubMed Central

    Sikoski, Paul; Trybus, James; Cline, J Mark; Muhammad, F Salih; Eckhoff, Andrew; Tan, Josh; Lockard, Mandy; Jolley, Tammy; Britt, Susan; Kock, Nancy D

    2008-01-01

    A 44-mo-old, female, nulliparous New Zealand White Rabbit (Oryctolagus cuniculus) presented with bilaterally diffusely enlarged mammary glands with enlarged, discolored teats that exuded brown, mucoid discharge. The complete blood count and serum chemistry panels were within normal limits, bacteria were not isolated from a culture of the discharge, and the clinical signs did not resolve with antibiotic treatment. Computed tomography and serum prolactin levels supported the diagnosis of mammary gland dysplasia, possibly due to a prolactin-secreting pituitary adenoma. Histologic evaluation confirmed the presence of a pituitary adenoma, mammary hyperplasia, dysplasia, and cystic mammary adenocarcinoma. Immunohistochemical staining confirmed the presence of abundant prolactin secreting cells in the pituitary adenoma. This is the second report of hyperprolactinemia with mammary dysplasia in rabbits, and the first report of cystic mammary adenocarcinoma associated with a prolactin-secreting pituitary adenoma in a rabbit. PMID:18589874

  11. Brain Ultrasonography Findings in Neonatal Seizure; a Cross-sectional Study.

    PubMed

    Nabavi, Seyed Saeed; Partovi, Parinaz

    2017-01-01

    Screening of newborns with seizure, who have curable pathologic brain findings, might be able to improve their final outcome by accelerating treatment intervention. The present study aimed to evaluate the brain ultrasonography findings of newborns hospitalized with complaint of seizure. The present cross-sectional study designed to evaluate brain ultrasonography findings of hospitalized newborns complaining seizure. Neonatal seizure was defined as presence of tonic, clonic, myoclonic, and subtle attacks in 1 - 28 day old newborns. 100 newborns with the mean age of 5.82 ± 6.29 days were evaluated (58% male). Most newborns were in the < 10 days age range (76%), term (83%) and with normal birth weight (81%). 22 (22%) of the ultrasonography examinations showed a pathologic finding. A correlation was only found between birth age and probability of the presence of a pathologic problem in the brain as the frequency of these problems was significantly higher in pre-term newborns (p = 0.023). Based on the findings of the present study, frequency of pathologic findings in neonatal brain ultrasonography was 22%. Hemorrhage (12%) and hydrocephaly (7%) were the most common findings. The only factor correlating with increased probability of positive findings was the newborns being pre-term.

  12. Peripheral Serotonin Regulates Maternal Calcium Trafficking in Mammary Epithelial Cells during Lactation in Mice

    PubMed Central

    Laporta, Jimena; Keil, Kimberly P.; Vezina, Chad M.; Hernandez, Laura L.

    2014-01-01

    Lactation is characterized by massive transcellular flux of calcium, from the basolateral side of the mammary alveolar epithelium (blood) into the ductal lumen (milk). Regulation of calcium transport during lactation is critical for maternal and neonatal health. The monoamine serotonin (5-HT) is synthesized by the mammary gland and functions as a homeostatic regulation of lactation. Genetic ablation of tryptophan hydroxylase 1 (Tph1), which encodes the rate-limiting enzyme in non-neuronal serotonin synthesis, causes a deficiency in circulating serotonin. As a consequence maternal calcium concentrations decrease, mammary epithelial cell morphology is altered, and cell proliferation is decreased during lactation. Here we demonstrate that serotonin deficiency decreases the expression and disrupts the normal localization of calcium transporters located in the apical (PMCA2) and basolateral (CaSR, ORAI-1) membranes of the lactating mammary gland. In addition, serotonin deficiency decreases the mRNA expression of calcium transporters located in intracellular compartments (SERCA2, SPCA1 and 2). Mammary expression of serotonin receptor isoform 2b and its downstream pathways (PLCβ3, PKC and MAP-ERK1/2) are also decreased by serotonin deficiency, which might explain the numerous phenotypic alterations described above. In most cases, addition of exogenous 5-hydroxy-L-tryptophan to the Tph1 deficient mice rescued the phenotype. Our data supports the hypothesis that serotonin is necessary for proper mammary gland structure and function, to regulate blood and mammary epithelial cell transport of calcium during lactation. These findings can be applicable to the treatment of lactation-induced hypocalcemia in dairy cows and can have profound implications in humans, given the wide-spread use of selective serotonin reuptake inhibitors as antidepressants during pregnancy and lactation. PMID:25299122

  13. SU-E-I-59: Investigation of the Usefulness of a Standard Deviation and Mammary Gland Density as Indexes for Mammogram Classification.

    PubMed

    Takarabe, S; Yabuuchi, H; Morishita, J

    2012-06-01

    To investigate the usefulness of the standard deviation of pixel values in a whole mammary glands region and the percentage of a high- density mammary glands region to a whole mammary glands region as features for classification of mammograms into four categories based on the ACR BI-RADS breast composition. We used 36 digital mediolateral oblique view mammograms (18 patients) approved by our IRB. These images were classified into the four categories of breast compositions by an experienced breast radiologist and the results of the classification were regarded as a gold standard. First, a whole mammary region in a breast was divided into two regions such as a high-density mammary glands region and a low/iso-density mammary glands region by using a threshold value that was obtained from the pixel values corresponding to a pectoral muscle region. Then the percentage of a high-density mammary glands region to a whole mammary glands region was calculated. In addition, as a new method, the standard deviation of pixel values in a whole mammary glands region was calculated as an index based on the intermingling of mammary glands and fats. Finally, all mammograms were classified by using the combination of the percentage of a high-density mammary glands region and the standard deviation of each image. The agreement rates of the classification between our proposed method and gold standard was 86% (31/36). This result signified that our method has the potential to classify mammograms. The combination of the standard deviation of pixel values in a whole mammary glands region and the percentage of a high-density mammary glands region to a whole mammary glands region was available as features to classify mammograms based on the ACR BI- RADS breast composition. © 2012 American Association of Physicists in Medicine.

  14. Cripto-1 Ablation Disrupts Alveolar Development in the Mouse Mammary Gland through a Progesterone Receptor–Mediated Pathway

    PubMed Central

    Klauzinska, Malgorzata; McCurdy, David; Rangel, Maria Cristina; Vaidyanath, Arun; Castro, Nadia P.; Shen, Michael M.; Gonzales, Monica; Bertolette, Daniel; Bianco, Caterina; Callahan, Robert; Salomon, David S.; Raafat, Ahmed

    2016-01-01

    Cripto-1, a member of the epidermal growth factor–Cripto-1/FRL-1/Cryptic family, is critical for early embryonic development. Together with its ligand Nodal, Cripto-1 has been found to be associated with the undifferentiated status of mouse and human embryonic stem cells. Several studies have clearly shown that Cripto-1 is involved in regulating branching morphogenesis and epithelial-mesenchymal transition of the mammary gland both in vitro and in vivo and together with the cofactor GRP78 is critical for the maintenance of mammary stem cells ex vivo. Our previous studies showed that mammary-specific overexpression of human Cripto-1 exhibited dramatic morphological alterations in nulliparous mice mammary glands. The present study shows a novel mechanism for Cripto-1 regulation of mammary gland development through direct effects on progesterone receptor expression and pathways regulated by progesterone in the mammary gland. We demonstrate a strict temporal regulation of mouse Cripto-1 (mCripto-1) expression that occurs during mammary gland development and a stage-specific function of mCripto-1 signaling during mammary gland development. Our data suggest that Cripto-1, like the progesterone receptor, is not required for the initial ductal growth but is essential for subsequent side branching and alveologenesis during the initial stages of pregnancy. Dissection of the mechanism by which this occurs indicates that mCripto-1 activates receptor activator NF-κB/receptor activator NF-κB ligand, and NF-κB signaling pathways. PMID:26429739

  15. The Ron Receptor Tyrosine Kinase Negatively Regulates Mammary Gland Branching Morphogenesis

    PubMed Central

    Meyer, Sara E.; Zinser, Glendon M.; Stuart, William D.; Pathrose, Peterson; Waltz, Susan E.

    2009-01-01

    The Ron receptor tyrosine kinase is expressed in normal breast tissue and is overexpressed in approximately 50% of human breast cancers. Despite the recent studies on Ron in breast cancer, nothing is known about the importance of this protein during breast development. To investigate the functional significance of Ron in the normal mammary gland, we compared mammary gland development in wild-type mice to mice containing a targeted ablation of the tyrosine kinase (TK) signaling domain of Ron (TK−/−). Mammary glands from RonTK−/− mice exhibited accelerated pubertal development including significantly increased ductal extension and branching morphogenesis. While circulating levels of estrogen, progesterone, and overall rates of epithelial cell turnover were unchanged, significant increases in phosphorylated MAPK, which predominantly localized to the epithelium, were associated with increased branching morphogenesis. Additionally, purified RonTK−/− epithelial cells cultured ex vivo exhibited enhanced branching morphogenesis, which was reduced upon MAPK inhibition. Microarray analysis of pubertal RonTK−/− glands revealed 393 genes temporally impacted by Ron expression with significant changes observed in signaling networks regulating development, morphogenesis, differentiation, cell motility, and adhesion. In total, these studies represent the first evidence of a role for the Ron receptor tyrosine kinase as a critical negative regulator of mammary development. PMID:19576199

  16. Experimental infection of bovine mammary gland with prototheca zopfii genotype 1.

    PubMed

    Ito, Takaaki; Kano, Rui; Sobukawa, Hideto; Ogawa, Jin; Honda, Yayoi; Hosoi, Yoshihiro; Shibuya, Hisashi; Sato, Tsuneo; Hasegawa, Atsuhiko; Kamata, Hiroshi

    2011-01-01

    Prototheca zopfii is divided into three genotypes, one of which, P. zopfii genotype 2, appears to be the main causative agent of bovine protothecal mastitis. However, the difference in pathogenicity between genotypes 1 and 2 has not been well investigated. In the present study, we experimentally infected normal bovine mammary gland with P. zopfii genotype 1 to investigate its pathogenicity. The mammary gland infected with P. zopfii genotype 1 showed no clinical signs. However, the histopathologic features of the infected mammary gland consisted of interstitial infiltrates of macrophages, plasma cells, lymphocytes, and fibroblasts with neutrophils in acinar lumens. Algae were present in macrophages and free in the alveolar lumens and the interstitium. Histopathology of the resultant tissue samples revealed that genotype 1 also induced a granulomatous lesion in the cow teat, similar to the mastitis lesion due to genotype 2.

  17. Neem leaf extract inhibits mammary carcinogenesis by altering cell proliferation, apoptosis, and angiogenesis

    PubMed Central

    Arumugam, Arunkumar; Agullo, Pamela; Boopalan, Thiyagarajan; Nandy, Sushmita; Lopez, Rebecca; Gutierrez, Christina; Narayan, Mahesh; Rajkumar, Lakshmanaswamy

    2014-01-01

    Plant-based medicines are useful in the treatment of cancer. Many breast cancer patients use complementary and alternative medicine in parallel with conventional treatments. Neem is historically well known in Asia and Africa as a versatile medicinal plant with a wide spectrum of biological activities. The experiments reported herein determined whether the administration of an ethanolic fraction of Neem leaf (EFNL) inhibits progression of chemical carcinogen-induced mammary tumorigenesis in rat models. Seven-week-old female Sprague Dawley rats were given a single intraperitoneal injection of N-methyl-N-nitrosourea (MNU). Upon the appearance of palpable mammary tumors, the rats were divided into vehicle-treated control groups and EFNL-treated groups. Treatment with EFNL inhibited MNU-induced mammary tumor progression. EFNL treatment was also highly effective in reducing mammary tumor burden and in suppressing mammary tumor progression even after the cessation of treatment. Further, we found that EFNL treatment effectively upregulated proapoptotic genes and proteins such as p53, B cell lymphoma-2 protein (Bcl-2)-associated X protein (Bax), Bcl-2-associated death promoter protein (Bad) caspases, phosphatase and tensin homolog gene (PTEN), and c-Jun N-terminal kinase (JNK). In contrast, EFNL treatment caused downregulation of anti-apoptotic (Bcl-2), angiogenic proteins (angiopoietin and vascular endothelial growth factor A [VEGF-A]), cell cycle regulatory proteins (cyclin D1, cyclin-dependent kinase 2 [Cdk2], and Cdk4), and pro-survival signals such as NFκB, mitogen-activated protein kinase 1 (MAPK1). The data obtained in this study demonstrate that EFNL exert a potent anticancer effect against mammary tumorigenesis by altering key signaling pathways. PMID:24146019

  18. Left-right analysis of mammary gland development in retinoid X receptor-α+/- mice.

    PubMed

    Robichaux, Jacqulyne P; Fuseler, John W; Patel, Shrusti S; Kubalak, Steven W; Hartstone-Rose, Adam; Ramsdell, Ann F

    2016-12-19

    Left-right (L-R) differences in mammographic parenchymal patterns are an early predictor of breast cancer risk; however, the basis for this asymmetry is unknown. Here, we use retinoid X receptor alpha heterozygous null (RXRα +/- ) mice to propose a developmental origin: perturbation of coordinated anterior-posterior (A-P) and L-R axial body patterning. We hypothesized that by analogy to somitogenesis-in which retinoic acid (RA) attenuation causes anterior somite pairs to develop L-R asynchronously-that RA pathway perturbation would likewise result in asymmetric mammary development. To test this, mammary glands of RXRα +/- mice were quantitatively assessed to compare left- versus right-side ductal epithelial networks. Unlike wild-type controls, half of the RXRα +/- thoracic mammary gland (TMG) pairs exhibited significant L-R asymmetry, with left-side reduction in network size. In RXRα +/- TMGs in which symmetry was maintained, networks had bilaterally increased size, with left networks showing greater variability in area and pattern. Reminiscent of posterior somites, whose bilateral symmetry is refractory to RA attenuation, inguinal mammary glands (IMGs) also had bilaterally increased network size, but no loss of symmetry. Together, these results demonstrate that mammary glands exhibit differential A-P sensitivity to RXRα heterozygosity, with ductal network symmetry markedly compromised in anterior but not posterior glands. As TMGs more closely model human breast development than IMGs, these findings raise the possibility that for some women, breast cancer risk may initiate with subtle axial patterning defects that result in L-R asymmetric growth and pattern of the mammary ductal epithelium.This article is part of the themed issue 'Provocative questions in left-right asymmetry'. © 2016 The Author(s).

  19. Ultrasonography of hydronephrosis in the newborn: a practical review

    PubMed Central

    2016-01-01

    Widespread use of fetal ultrasonography is accompanied by more frequent detection of antenatal hydronephrosis. Therefore, sonographic evaluation of neonates with a history of antenatal hydronephrosis is becoming more widespread. As an initial postnatal non-invasive imaging modality, ultrasonography is used to screen for persistence of hydronephrosis, determine the level and severity of obstruction, and contribute to appropriate diagnosis and treatment. This review aims to provide a practical overview of the sonographic evaluation of neonatal hydronephrosis and to describe the sonographic findings of conditions associated with hydronephrosis in the newborn. PMID:27156562

  20. Distinct Luminal-Type Mammary Carcinomas Arise from Orthotopic Trp53-Null Mammary Transplantation of Juvenile versus Adult Mice

    DOE PAGES

    Nguyen, David H.; Ouyang, Haoxu; Mao, Jian-Hua; ...

    2014-12-01

    Age and physiologic status, such as menopause, are risk factors for breast cancer. Less clear is what factors influence the diversity of breast cancer. In this study, we investigated the effect of host age on the distribution of tumor subtypes in mouse mammary chimera consisting of wild-type hosts and Trp53 nullizygous epithelium, which undergoes a high rate of neoplastic transformation. Wild-type mammary glands cleared of endogenous epithelium at 3 weeks of age were subsequently transplanted during puberty (5 weeks) or at maturation (10 weeks) with syngeneic Trp53-null mammary tissue fragments and monitored for one year. Tumors arose sooner from adultmore » hosts (AH) compared with juvenile hosts (JH). However, compared with AH tumors, JH tumors grew several times faster, were more perfused, exhibited a two-fold higher mitotic index, and were more highly positive for insulin-like growth factor receptor phosphorylation. Most tumors in each setting were estrogen receptor (ER)-positive (80% JH vs. 70% AH), but JH tumors were significantly more ER-immunoreactive (P = 0.0001) than AH tumors. A differential expression signature (JvA) of juvenile versus adult tumors revealed a luminal transcriptional program. Centroids of the human homologs of JvA genes showed that JH tumors were more like luminal A tumors and AH tumors were more like luminal B tumors. Hierarchical clustering with the JvA human ortholog gene list segregated luminal A and luminal B breast cancers across datasets. Lastly, these data support the notion that age-associated host physiology greatly influences the intrinsic subtype of breast cancer.« less

  1. Distinct Luminal-Type Mammary Carcinomas Arise from Orthotopic Trp53-Null Mammary Transplantation of Juvenile versus Adult Mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nguyen, David H.; Ouyang, Haoxu; Mao, Jian-Hua

    Age and physiologic status, such as menopause, are risk factors for breast cancer. Less clear is what factors influence the diversity of breast cancer. In this study, we investigated the effect of host age on the distribution of tumor subtypes in mouse mammary chimera consisting of wild-type hosts and Trp53 nullizygous epithelium, which undergoes a high rate of neoplastic transformation. Wild-type mammary glands cleared of endogenous epithelium at 3 weeks of age were subsequently transplanted during puberty (5 weeks) or at maturation (10 weeks) with syngeneic Trp53-null mammary tissue fragments and monitored for one year. Tumors arose sooner from adultmore » hosts (AH) compared with juvenile hosts (JH). However, compared with AH tumors, JH tumors grew several times faster, were more perfused, exhibited a two-fold higher mitotic index, and were more highly positive for insulin-like growth factor receptor phosphorylation. Most tumors in each setting were estrogen receptor (ER)-positive (80% JH vs. 70% AH), but JH tumors were significantly more ER-immunoreactive (P = 0.0001) than AH tumors. A differential expression signature (JvA) of juvenile versus adult tumors revealed a luminal transcriptional program. Centroids of the human homologs of JvA genes showed that JH tumors were more like luminal A tumors and AH tumors were more like luminal B tumors. Hierarchical clustering with the JvA human ortholog gene list segregated luminal A and luminal B breast cancers across datasets. Lastly, these data support the notion that age-associated host physiology greatly influences the intrinsic subtype of breast cancer.« less

  2. Differences in the ribosomes prepared from lactating and non-lactating bovine mammary gland

    PubMed Central

    Herrington, M. D.; Hawtrey, A. O.

    1971-01-01

    1. Ribosomes prepared from bovine lactating mammary gland are able to synthesize protein, whereas similar preparations from non-lactating glands are not. Washing the ribosome suspensions through a medium containing 0.5m-ammonium chloride enhanced their ability to incorporate phenylalanine into polyphenylalanine. 2. Ribosomes isolated from non-lactating bovine mammary gland, in contrast with those from rat liver and lactating mammary gland, contained significant amounts of extraneous nucleases. These enzymes could be removed by washing with a medium A buffer containing 0.5m-ammonium chloride. 3. Only those ribosomes from functionally active tissues were able to bind polyuridylic acid and phenylalanyl-tRNA. PMID:5165653

  3. Mammary and femoral hydatid cysts.

    PubMed

    Shamim, Muhammad

    2010-08-01

    Hydatid cyst disease most commonly affects liver and lungs, but it can affect all viscera and soft tissues of the body. Simultaneous mammary and femoral hydatid cysts, without any other visceral involvement, are extremely rare. This is a case report of 25-years-old female, presenting with lump in left breast mimicking fibroadenoma and lump in right thigh mimicking fibroma. Both turned out to be hydatid cysts.

  4. Repressor of Estrogen Receptor Activity (REA) Is Essential for Mammary Gland Morphogenesis and Functional Activities: Studies in Conditional Knockout Mice

    PubMed Central

    Park, Sunghee; Zhao, Yuechao; Yoon, Sangyeon; Xu, Jianming; Liao, Lan; Lydon, John; DeMayo, Franco; O'Malley, Bert W.

    2011-01-01

    Estrogen receptor (ER) is a key regulator of mammary gland development and is also implicated in breast tumorigenesis. Because ER-mediated activities depend critically on coregulator partner proteins, we have investigated the consequences of reduction or loss of function of the coregulator repressor of ER activity (REA) by conditionally deleting one allele or both alleles of the REA gene at different stages of mammary gland development. Notably, we find that heterozygosity and nullizygosity for REA result in very different mammary phenotypes and that REA has essential roles in the distinct morphogenesis and functions of the mammary gland at different stages of development, pregnancy, and lactation. During puberty, mice homozygous null for REA in the mammary gland (REAf/f PRcre/+) showed severely impaired mammary ductal elongation and morphogenesis, whereas mice heterozygous for REA (REAf/+ PRcre/+) displayed accelerated mammary ductal elongation, increased numbers of terminal end buds, and up-regulation of amphiregulin, the major paracrine mediator of estrogen-induced ductal morphogenesis. During pregnancy and lactation, mice with homozygous REA gene deletion in mammary epithelium (REAf/f whey acidic protein-Cre) showed a loss of lobuloalveolar structures and increased apoptosis of mammary alveolar epithelium, leading to impaired milk production and significant reduction in growth of their offspring, whereas body weights of the offspring nursed by females heterozygous for REA were slightly greater than those of control mice. Our findings reveal that REA is essential for mammary gland development and has a gene dosage-dependent role in the regulation of stage-specific physiological functions of the mammary gland. PMID:21862609

  5. Mena deficiency delays tumor progression and decreases metastasis in polyoma middle-T transgenic mouse mammary tumors.

    PubMed

    Roussos, Evanthia T; Wang, Yarong; Wyckoff, Jeffrey B; Sellers, Rani S; Wang, Weigang; Li, Jiufeng; Pollard, Jeffrey W; Gertler, Frank B; Condeelis, John S

    2010-01-01

    The actin binding protein Mammalian enabled (Mena), has been implicated in the metastatic progression of solid tumors in humans. Mena expression level in primary tumors is correlated with metastasis in breast, cervical, colorectal and pancreatic cancers. Cells expressing high Mena levels are part of the tumor microenvironment for metastasis (TMEM), an anatomical structure that is predictive for risk of breast cancer metastasis. Previously we have shown that forced expression of Mena adenocarcinoma cells enhances invasion and metastasis in xenograft mice. Whether Mena is required for tumor progression is still unknown. Here we report the effects of Mena deficiency on tumor progression, metastasis and on normal mammary gland development. To investigate the role of Mena in tumor progression and metastasis, Mena deficient mice were intercrossed with mice carrying a transgene expressing the polyoma middle T oncoprotein, driven by the mouse mammary tumor virus. The progeny were investigated for the effects of Mena deficiency on tumor progression via staging of primary mammary tumors and by evaluation of morbidity. Stages of metastatic progression were investigated using an in vivo invasion assay, intravital multiphoton microscopy, circulating tumor cell burden, and lung metastases. Mammary gland development was studied in whole mount mammary glands of wild type and Mena deficient mice. Mena deficiency decreased morbidity and metastatic dissemination. Loss of Mena increased mammary tumor latency but had no affect on mammary tumor burden or histologic progression to carcinoma. Elimination of Mena also significantly decreased epidermal growth factor (EGF) induced in vivo invasion, in vivo motility, intravasation and metastasis. Non-tumor bearing mice deficient for Mena also showed defects in mammary gland terminal end bud formation and branching. Deficiency of Mena decreases metastasis by slowing tumor progression and reducing tumor cell invasion and intravasation. Mena

  6. Salvia officinalis L. induces alveolar bud growing in adult female rat mammary glands

    PubMed Central

    Monsefi, Malihezaman; Abedian, Mehrnaz; Azarbahram, Zahra; Ashraf, Mohammad Javad

    2015-01-01

    Objectives: In traditional medicine Salvia officinalis (sage) has been used as menstrual cycle regulator. In the present study the effects of sage extract on breast tissue were examined. Materials and Methods: Fourteen female rats were divided into two groups: 1) Distilled water-treated rats (Con) that were gavaged with 1ml distilled water and 2) Saliva officinalis hydroalcoholic extract (SHE)-treated rats that were gavaged with 30mg/kg/body weight of sage extract for 30 days. The estrus cycle changes were monitored by daily examination of vaginal smear. Whole mounts of right pelvic breast were spread on the slide and stained by carmine. The number of alveolar buds (ABs) type 1 and 2 and lobules of mammary gland were scored. Tissue sections of left pelvic mammary gland were prepared and its histomorphometrical changes were measured. Blood samples were taken from dorsal aorta and estradiol and progesterone concentrations were measured using radioimmunoassay. Results: Estrous cycles decreased significantly in SHE-treated animals. The number of alveolar buds and lobules in mammary gland whole mount of SHE-treated group were higher than the Con group. The number and diameter of ducts in histological section of mammary gland in SHE-treated group increased as compared to the Con group. Conclusion: Sage promotes alveologenesis of mammary glands and it can be used as a lactiferous herb. PMID:26693413

  7. Identification of genetic loci that control mammary tumor susceptibility through the host microenvironment

    DOE PAGES

    Zhang, Pengju; Lo, Alvin; Huang, Yurong; ...

    2015-03-09

    The interplay between host genetics, tumor microenvironment and environmental exposure in cancer susceptibility remains poorly understood. Here we assessed the genetic control of stromal mediation of mammary tumor susceptibility to low dose ionizing radiation (LDIR) using backcrossed F1 into BALB/c (F1Bx) between cancer susceptible (BALB/c) and resistant (SPRET/EiJ) mouse strains. Tumor formation was evaluated after transplantation of non-irradiated Trp53-/- BALB/c mammary gland fragments into cleared fat pads of F1Bx hosts. Genome-wide linkage analysis revealed 2 genetic loci that constitute the baseline susceptibility via host microenvironment. However, once challenged with LDIR, we discovered 13 additional loci that were enriched for genesmore » involved in cytokines, including TGFβ1 signaling. Surprisingly, LDIR-treated F1Bx cohort significantly reduced incidence of mammary tumors from Trp53-/- fragments as well as prolonged tumor latency, compared to sham-treated controls. We demonstrated further that plasma levels of specific cytokines were significantly correlated with tumor latency. Using an ex vivo 3-D assay, we confirmed TGFβ1 as a strong candidate for reduced mammary invasion in SPRET/EiJ, which could explain resistance of this strain to mammary cancer risk following LDIR. Our results open possible new avenues to understand mechanisms of genes operating via the stroma that affect cancer risk from external environmental exposures.« less

  8. Identification of genetic loci that control mammary tumor susceptibility through the host microenvironment

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Pengju; Lo, Alvin; Huang, Yurong

    The interplay between host genetics, tumor microenvironment and environmental exposure in cancer susceptibility remains poorly understood. Here we assessed the genetic control of stromal mediation of mammary tumor susceptibility to low dose ionizing radiation (LDIR) using backcrossed F1 into BALB/c (F1Bx) between cancer susceptible (BALB/c) and resistant (SPRET/EiJ) mouse strains. Tumor formation was evaluated after transplantation of non-irradiated Trp53-/- BALB/c mammary gland fragments into cleared fat pads of F1Bx hosts. Genome-wide linkage analysis revealed 2 genetic loci that constitute the baseline susceptibility via host microenvironment. However, once challenged with LDIR, we discovered 13 additional loci that were enriched for genesmore » involved in cytokines, including TGFβ1 signaling. Surprisingly, LDIR-treated F1Bx cohort significantly reduced incidence of mammary tumors from Trp53-/- fragments as well as prolonged tumor latency, compared to sham-treated controls. We demonstrated further that plasma levels of specific cytokines were significantly correlated with tumor latency. Using an ex vivo 3-D assay, we confirmed TGFβ1 as a strong candidate for reduced mammary invasion in SPRET/EiJ, which could explain resistance of this strain to mammary cancer risk following LDIR. Our results open possible new avenues to understand mechanisms of genes operating via the stroma that affect cancer risk from external environmental exposures.« less

  9. Targeted overexpression of EZH2 in the mammary gland disrupts ductal morphogenesis and causes epithelial hyperplasia.

    PubMed

    Li, Xin; Gonzalez, Maria E; Toy, Katherine; Filzen, Tracey; Merajver, Sofia D; Kleer, Celina G

    2009-09-01

    The Polycomb group protein enhancer of zeste homolog 2 (EZH2), which has roles during development of numerous tissues, is a critical regulator of cell type identity. Overexpression of EZH2 has been detected in invasive breast carcinoma tissue samples and is observed in human breast tissue samples of morphologically normal lobules up to 12 years before the development of breast cancer. The function of EZH2 during preneoplastic progression in the mammary gland is unknown. To investigate the role of EZH2 in the mammary gland, we targeted the expression of EZH2 to mammary epithelial cells using the mouse mammary tumor virus long terminal repeat. EZH2 overexpression resulted in aberrant terminal end bud architecture. By the age of 4 months, 100% of female mouse mammary tumor virus-EZH2 virgin mice developed intraductal epithelial hyperplasia resembling the human counterpart accompanied by premature differentiation of ductal epithelial cells and up-regulation of the luminal marker GATA-3. In addition, remodeling of the mammary gland after parturition was impaired and EZH2 overexpression caused delayed involution. Mechanistically, we found that EZH2 physically interacts with beta-catenin, inducing beta-catenin nuclear accumulation in mammary epithelial cells and activating Wnt/beta-catenin signaling. The biological significance of these data to human hyperplasias is demonstrated by EZH2 up-regulation and colocalization with beta-catenin in human intraductal epithelial hyperplasia, the earliest histologically identifiable precursor of breast carcinoma.

  10. Targeted Overexpression of EZH2 in the Mammary Gland Disrupts Ductal Morphogenesis and Causes Epithelial Hyperplasia

    PubMed Central

    Li, Xin; Gonzalez, Maria E.; Toy, Katherine; Filzen, Tracey; Merajver, Sofia D.; Kleer, Celina G.

    2009-01-01

    The Polycomb group protein enhancer of zeste homolog 2 (EZH2), which has roles during development of numerous tissues, is a critical regulator of cell type identity. Overexpression of EZH2 has been detected in invasive breast carcinoma tissue samples and is observed in human breast tissue samples of morphologically normal lobules up to 12 years before the development of breast cancer. The function of EZH2 during preneoplastic progression in the mammary gland is unknown. To investigate the role of EZH2 in the mammary gland, we targeted the expression of EZH2 to mammary epithelial cells using the mouse mammary tumor virus long terminal repeat. EZH2 overexpression resulted in aberrant terminal end bud architecture. By the age of 4 months, 100% of female mouse mammary tumor virus-EZH2 virgin mice developed intraductal epithelial hyperplasia resembling the human counterpart accompanied by premature differentiation of ductal epithelial cells and up-regulation of the luminal marker GATA-3. In addition, remodeling of the mammary gland after parturition was impaired and EZH2 overexpression caused delayed involution. Mechanistically, we found that EZH2 physically interacts with β-catenin, inducing β-catenin nuclear accumulation in mammary epithelial cells and activating Wnt/β-catenin signaling. The biological significance of these data to human hyperplasias is demonstrated by EZH2 up-regulation and colocalization with β-catenin in human intraductal epithelial hyperplasia, the earliest histologically identifiable precursor of breast carcinoma. PMID:19661437

  11. Complex mammary carcinoma with metastases to lymph nodes, subcutaneous tissue, and multiple joints in a dog.

    PubMed

    McCourt, Maggie R; Dieterly, Alexandra M; Mackey, Paige E; Lyon, Shane D; Rizzi, Theresa E; Ritchey, Jerry W

    2018-05-07

    An 8-year-old, intact female, mixed-breed dog presented to the Oklahoma State University Boren Veterinary Medical Teaching Hospital for evaluation of progressive lameness and joint effusion of multiple joints. Physical examination revealed joint effusion of the elbow, hock, and stifle joints bilaterally, enlarged left axillary and right popliteal lymph nodes, a subcutaneous mass over the left elbow, and a subcutaneous mass involving the left second and third mammary glands. Cytologic examination of the mammary mass, enlarged lymph nodes, and joint fluid from most affected joints revealed a monomorphic population of loosely cohesive neoplastic epithelial cells. The patient was humanely euthanized, and subsequent necropsy with histopathologic examination revealed a complex mammary carcinoma with metastases to enlarged lymph nodes, subcutaneous tissue over the left elbow, and the synovium of multiple joints. Immunohistochemical stains were performed and showed diffusely positive pan cytokeratin, CK8/18, and CK19 staining in the neoplastic luminal epithelial cells of the mammary carcinoma, synovium, and lymph nodes, and showed diffusely positive vimentin staining of the myoepithelial cells. Myoepithelial calponin positivity was diffuse in the mammary mass and lymph nodes but minimal in the synovium. Only the mammary mass showed p63 positivity. Metastatic mammary neoplasia is relatively common in dogs; however, metastasis to the synovium has only been reported once previously in the literature. This is the first case utilizing immunohistochemistry for confirmation and characterization of metastases. © 2018 American Society for Veterinary Clinical Pathology.

  12. Metabolomics Reveals Aryl Hydrocarbon Receptor Activation Induces Liver and Mammary Gland Metabolic Dysfunction in Lactating Mice.

    PubMed

    Belton, Kerry R; Tian, Yuan; Zhang, Limin; Anitha, Mallappa; Smith, Philip B; Perdew, Gary H; Patterson, Andrew D

    2018-04-06

    The liver and the mammary gland have complementary metabolic roles during lactation. Substrates synthesized by the liver are released into the circulation and are taken up by the mammary gland for milk production. The aryl hydrocarbon receptor (AHR) has been identified as a lactation regulator in mice, and its activation has been associated with myriad morphological, molecular, and functional defects such as stunted gland development, decreased milk production, and changes in gene expression. In this study, we identified adverse metabolic changes in the lactation network (mammary, liver, and serum) associated with AHR activation using 1 H nuclear magnetic resonance (NMR)-based metabolomics. Pregnant mice expressing Ahr d (low affinity) or Ahr b (high affinity) were fed diets containing beta naphthoflavone (BNF), a potent AHR agonist. Mammary, serum, and liver metabolomics analysis identified significant changes in lipid and TCA cycle intermediates in the Ahr b mice. We observed decreased amino acid and glucose levels in the mammary gland extracts of Ahr b mice fed BNF. The serum of BNF fed Ahr b mice had significant changes in LDL/VLDL (increased) and HDL, PC, and GPC (decreased). Quantitative PCR analysis revealed ∼50% reduction in the expression of key lactogenesis mammary genes including whey acid protein, α-lactalbumin, and β-casein. We also observed morphologic and developmental disruptions in the mammary gland that are consistent with previous reports. Our observations support that AHR activity contributes to metabolism regulation in the lactation network.

  13. Radiation induces genomic instability and mammary ductal dysplasia in Atm heterozygous mice

    NASA Technical Reports Server (NTRS)

    Weil, M. M.; Kittrell, F. S.; Yu, Y.; McCarthy, M.; Zabriskie, R. C.; Ullrich, R. L.

    2001-01-01

    Ataxia-telangiectasia (AT) is a genetic syndrome resulting from the inheritance of two defective copies of the ATM gene that includes among its stigmata radiosensitivity and cancer susceptibility. Epidemiological studies have demonstrated that although women with a single defective copy of ATM (AT heterozygotes) appear clinically normal, they may never the less have an increased relative risk of developing breast cancer. Whether they are at increased risk for radiation-induced breast cancer from medical exposures to ionizing radiation is unknown. We have used a murine model of AT to investigate the effect of a single defective Atm allele, the murine homologue of ATM, on the susceptibility of mammary epithelial cells to radiation-induced transformation. Here we report that mammary epithelial cells from irradiated mice with one copy of Atm truncated in the PI-3 kinase domain were susceptible to radiation-induced genomic instability and generated a 10% incidence of dysplastic mammary ducts when transplanted into syngenic recipients, whereas cells from Atm(+/+) mice were stable and formed only normal ducts. Since radiation-induced ductal dysplasia is a precursor to mammary cancer, the results indicate that AT heterozygosity increases susceptibility to radiogenic breast cancer in this murine model system.

  14. Repression of mammary adipogenesis by genistein limits mammosphere formation of human MCF-7 cells

    USDA-ARS?s Scientific Manuscript database

    Mammary adipose tissue may contribute to breast cancer development and progression by altering neighboring epithelial cell behavior and phenotype through paracrine signaling. Dietary exposure to soy foods is associated with lower mammary tumor risk and reduced body weight and adiposity in humans and...

  15. Experimental study on the clinical effects of Xiaoru Sanjie Jiaonang on mammary glands hyperplasia and ki-67

    PubMed Central

    Zheng, Zi-Hao; Liu, Lin; Zou, Shi-Fang; Xu, Yu-Ting; Chen, Cui-Cui; Liang, Wen-Long; Guo, Bao-Liang; Wang, Yu; Zhu, Kai-Yuan; Liu, Jie-Na; Xu, Dan-Dan; Wang, Ji-Yan; Lin, Jia-Yan; Liu, Li; Zhang, Jian Guo; Chen, Xi

    2018-01-01

    Objective: This study aims to observe the effect and mechanism of Xiaoru Sanjie Jiaonang (XRSJ) on the treatment of mammary gland hyperplasia, and provide a theoretical basis and clinical evidence for clinical expansion. Methods: Japanese white rabbits were randomly divided into three groups: high-, middle- and low-dose groups; Xiaoyao Pill group; model control group; normal control group. The observation points were as follows: before XRSJ administration, three months after XRSJ administration, and three months after XRSJ discontinuance. Changes in breast height, morphological changes of the mammary gland under a light and electron microscope, and the expression of ki-67 were observed. At the same time, patients diagnosed with mammary gland hyperplasia at an Outpatient Clinic were selected and divided into treatment groups. These patients received XRSJ and Xiaoyao Pills, respectively, for one month, while patients in the control group did not receive any drug treatment. Clinical efficacy was observed while rechecking at the Outpatient Clinic after three months. Treatment with a therapeutic dose of XRSJ could significantly reduce breast height, decrease the number of lobules and acini in hyperplastic mammary glands and the layer number of ductal glandular epithelial cells, substantially lower the content of serum estradiol (E2), significantly downregulate the expression of ki-67 protein in mammary tissues, and inhibit mammary gland hyperplasia. Conclusion: XRSJ treatment can relieve mammary tissue hyperplastic lesions, reduce E2 levels and downregulate the expression of ki-67. It has a significant therapeutic effect on mammary gland hyperplasia. PMID:29636873

  16. Cripto-1 ablation disrupts alveolar development in the mouse mammary gland through a progesterone receptor-mediated pathway.

    PubMed

    Klauzinska, Malgorzata; McCurdy, David; Rangel, Maria Cristina; Vaidyanath, Arun; Castro, Nadia P; Shen, Michael M; Gonzales, Monica; Bertolette, Daniel; Bianco, Caterina; Callahan, Robert; Salomon, David S; Raafat, Ahmed

    2015-11-01

    Cripto-1, a member of the epidermal growth factor-Cripto-1/FRL-1/Cryptic family, is critical for early embryonic development. Together with its ligand Nodal, Cripto-1 has been found to be associated with the undifferentiated status of mouse and human embryonic stem cells. Several studies have clearly shown that Cripto-1 is involved in regulating branching morphogenesis and epithelial-mesenchymal transition of the mammary gland both in vitro and in vivo and together with the cofactor GRP78 is critical for the maintenance of mammary stem cells ex vivo. Our previous studies showed that mammary-specific overexpression of human Cripto-1 exhibited dramatic morphological alterations in nulliparous mice mammary glands. The present study shows a novel mechanism for Cripto-1 regulation of mammary gland development through direct effects on progesterone receptor expression and pathways regulated by progesterone in the mammary gland. We demonstrate a strict temporal regulation of mouse Cripto-1 (mCripto-1) expression that occurs during mammary gland development and a stage-specific function of mCripto-1 signaling during mammary gland development. Our data suggest that Cripto-1, like the progesterone receptor, is not required for the initial ductal growth but is essential for subsequent side branching and alveologenesis during the initial stages of pregnancy. Dissection of the mechanism by which this occurs indicates that mCripto-1 activates receptor activator NF-κB/receptor activator NF-κB ligand, and NF-κB signaling pathways. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  17. Inducible transgenics. New lessons on events governing the induction and commitment in mammary tumorigenesis.

    PubMed

    Hulit, J; Di Vizio, D; Pestell, R G

    2001-01-01

    Breast cancer arises from multiple genetic events that together contribute to the established, irreversible malignant phenotype. The development of inducible tissue-specific transgenics has allowed a careful dissection of the events required for induction and subsequent maintenance of tumorigenesis. Mammary gland targeted expression of oncogenic Ras or c-Myc is sufficient for the induction of mammary gland tumorigenesis in the rodent, and when overexpressed together the rate of tumor onset is substantially enhanced. In an exciting recent finding, D'Cruz et al discovered tetracycline-regulated c-Myc overexpression in the mammary gland induced invasive mammary tumors that regressed upon withdrawal of c-Myc expression. Almost one-half of the c-Myc-induced tumors harbored K-ras or N-ras gene point mutations, correlating with tumor persistence on withdrawal of c-Myc transgene expression. These findings suggest maintenance of tumorigenesis may involve a second mutation within the Ras pathway.

  18. Regulation of mammary gland sensitivity to thyroid hormones during the transition from pregnancy to lactation.

    PubMed

    Capuco, A V; Connor, E E; Wood, D L

    2008-10-01

    Thyroid hormones are galactopoietic and help to establish the mammary gland's metabolic priority during lactation. Expression patterns for genes that can alter tissue sensitivity to thyroid hormones and thyroid hormone activity were evaluated in the mammary gland and liver of cows at 53, 35, 20, and 7 days before expected parturition, and 14 and 90 days into the subsequent lactation. Transcript abundance for the three isoforms of iodothyronine deiodinase, type I (DIO1), type II (DIO2) and type III (DIO3), thyroid hormone receptors alpha1 (TRalpha1), alpha2 (TRalpha2) and beta1 (TRbeta1), and retinoic acid receptors alpha (RXRalpha) and gamma (RXRgamma), which act as coregulators of thyroid hormone receptor action, were evaluated by quantitative RT-PCR. The DIO3 is a 5-deiodinase that produces inactive iodothyronine metabolites, whereas DIO1 and DIO2 generate the active thyroid hormone, triiodothyronine, from the relatively inactive precursor, thyroxine. Low copy numbers of DIO3 transcripts were present in mammary gland and liver. DIO2 was the predominant isoform expressed in mammary gland and DIO1 was the predominant isoform expressed in liver. Quantity of DIO1 mRNA in liver tissues did not differ with physiological state, but tended to be lowest during lactation. Quantity of DIO2 mRNA in mammary gland increased during lactation (P < 0.05), with copy numbers at 90 days of lactation 6-fold greater than at 35 and 20 days prepartum. When ratios of DIO2/DIO3 mRNA were evaluated, the increase was more pronounced (>100-fold). Quantity of TRbeta1 mRNA in mammary gland increased with onset of lactation, whereas TRalpha1 and TRalpha2 transcripts did not vary with physiological state. Conversely, quantity of RXRalpha mRNA decreased during late gestation to low levels during early lactation. Data suggest that increased expression of mammary TRbeta1 and DIO2, and decreased RXRalpha, provide a mechanism to increase thyroid hormone activity within the mammary gland during

  19. Goat mammary gland expression of Cecropin B to inhibit bacterial pathogens causing mastitis.

    PubMed

    Luo, Chao-chao; Yin, De-yun; Gao, Xue-jun; Li, Qing-zhang; Zhang, Li

    2013-01-01

    The antibacterial peptide Cecropin B (CB), isolated from the giant silk moth, has been shown to effectively eliminate bacteria. In this study, the effects of transgenic CB on dairy goat mammary epithelial cells (DGMECs) and dairy goat mammary gland were investigated. The DNA of CB from silkworm was amplified by reverse transcription PCR (RT-PCR) and then fused to the eukaryotic expression vector pECFP-C1. The recombinant plasmid pECFP-Cecropin B (pECFP-CB) was used for the transfection of DGMECs, and the expression of transgenic CB and the antibacterial activity of it were confirmed by western blot and agar diffusion reaction respectively. The stable DGMEC line transfected by pECFP-CB was obtained by screening with G418. In vivo experiment, pECFP-CB was injected into dairy goat mammary gland, and also the expression and antibacterial activity of transgenic CB were confirmed. Results of this study: transgenic CB can be expressed in DGMECs and dairy goat mammary gland, and inhibit the mastitis caused by Staphylococcus aureus.

  20. Establishment and characterization of a lactating dairy goat mammary gland epithelial cell line.

    PubMed

    Tong, Hui-Li; Li, Qing-Zhang; Gao, Xue-Jun; Yin, De-Yun

    2012-03-01

    To study milk synthesis in dairy goat mammary gland, we had established an in vitro lactating dairy goat mammary epithelial cell (DGMEC) line. Mammary tissues of Guan Zhong dairy goats at 35 d of lactation were dispersed and cultured in a medium containing epithelial growth factor, insulin-like growth factor-1, insulin transferrin serum, and fetal bovine serum. Epithelial cells were enriched by digesting with 0.25% trypsin repeatedly to remove fibroblast cells and were identified as epithelial origin by staining with antibody against cytokeratine 18. The DGMECs displayed monolayer, cobble-stone, epithelial-like morphology, and formed alveoli-like structures and island monolayer aggregates which were the typical characteristics of mammary epithelial cells. A one-half logarithmically growth curve and cytoplasmic lipid droplets in these cells were observed. In this paper, we also studied the lactating function of DGMECs. Results showed that DGMECs could secrete lactose and β-casein. Lactating function of the cells had no obvious change after 48 h treated by insulin, while prolactin could obviously raise the secretion of milk proteins and lactose.

  1. The effects of spaceflight on mammary metabolism in pregnant rats

    NASA Technical Reports Server (NTRS)

    Plaut, K.; Maple, R.; Vyas, C.; Munaim, S.; Darling, A.; Casey, T.; Alberts, J. R.

    1999-01-01

    The effects of spaceflight on mammary metabolism of 10 pregnant rats was measured on Day 20 of pregnancy and after parturition. Rats were flown on the space shuttle from Day 11 through Day 20 of pregnancy. After their return to earth, glucose oxidation to carbon dioxide increased 43% (P < 0.05), and incorporation into fatty acids increased 300% (P < 0.005) compared to controls. It is unclear whether the enhanced glucose use is due to spaceflight or a response to landing. Casein mRNA and gross histology were not altered at Day 20 of pregnancy. Six rats gave birth (on Day 22 to 23 of pregnancy) and mammary metabolic activity was measured immediately postpartum. The earlier effects of spaceflight were no longer apparent. There was also no difference in expression of beta-casein mRNA. It is clear from these studies that spaceflight does not impair the normal development of the mammary gland, its ability to use glucose, nor the ability to express mRNA for a major milk protein.

  2. Hierarchy within the mammary STAT5-driven Wap super-enhancer

    PubMed Central

    Zeng, Xianke; Wang, Chaochen; Metser, Gil; Hennighausen, Lothar

    2016-01-01

    Super-enhancers comprise of dense transcription factor platforms highly enriched for active chromatin marks. A paucity of functional data led us to investigate their role in the mammary gland, an organ characterized by exceptional gene regulatory dynamics during pregnancy. ChIP-Seq for the master regulator STAT5, the glucocorticoid receptor, H3K27ac and MED1, identified 440 mammary-specific super-enhancers, half of which were associated with genes activated during pregnancy. We interrogated the Wap super-enhancer, generating mice carrying mutations in STAT5 binding sites within its three constituent enhancers. Individually, only the most distal site displayed significant enhancer activity. However, combinatorial mutations showed that the 1,000-fold gene induction relied on all enhancers. Disabling the binding sites of STAT5, NFIB and ELF5 in the proximal enhancer incapacitated the entire super-enhancer, suggesting an enhancer hierarchy. The identification of mammary-specific super-enhancers and the mechanistic exploration of the Wap locus provide insight into the complexity of cell-specific and hormone-regulated genes. PMID:27376239

  3. Enhanced mammary progesterone receptor-A isoform activity in the promotion of mammary tumor progression by dietary soy in rats

    USDA-ARS?s Scientific Manuscript database

    Dietary contribution to breast cancer risk, recurrence, and progression remains incompletely understood. Increased consumption of soy and soy isoflavones is associated with reduced mammary cancer susceptibility in women and in rodent models of carcinogenesis. In rats treated with N-Methyl-N-Nitrosou...

  4. Economic analysis of bedside ultrasonography (US) implementation in an Internal Medicine department.

    PubMed

    Testa, Americo; Francesconi, Andrea; Giannuzzi, Rosangela; Berardi, Silvia; Sbraccia, Paolo

    2015-12-01

    The economic crisis, the growing healthcare demand, and Defensive Medicine wastefulness, strongly recommend the restructuring of the entire medical network. New health technology, such as bedside ultrasonography, might successfully integrate the clinical approach optimizing the use of limited resources, especially in a person-oriented vision of medicine. Bedside ultrasonography is a safe and reliable technique, with worldwide expanding employment in various clinical settings, being considered as "the stethoscope of the 21st century". However, at present, bedside ultrasonography lacks economic analysis. We performed a Cost-Benefit Analysis "ex ante", with a break-even point computing, of bedside ultrasonography implementation in an Internal Medicine department in the mid-term. Number and kind estimation of bedside ultrasonographic studies were obtained by a retrospective study, whose data results were applied to the next 3-year period (foresight study). All 1980 foreseen bedside examinations, with prevailing multiorgan ultrasonographic studies, were considered to calculate direct and indirect costs, while specific and generic revenues were considered only after the first semester. Physician professional training, equipment purchase and working time represented the main fixed and variable cost items. DRG increase/appropriateness, hospitalization stay shortening and reduction of traditional ultrasonography examination requests mainly impacted on calculated revenues. The break-even point, i.e. the volume of activity at which revenues exactly equal total incurred costs, was calculated to be 734 US examinations, corresponding to € 81,998 and the time considered necessary to reach it resulting 406 days. Our economic analysis clearly shows that bedside ultrasonography implementation in clinical daily management of an Internal Medicine department can produce consistent savings, or economic profit according to managerial choices (i.e., considering public or private targets

  5. Stromal fibroblasts derived from mammary gland of bovine with mastitis display inflammation-specific changes

    PubMed Central

    Chen, Qing; He, Guiliang; Zhang, Wenyao; Xu, Tong; Qi, Hongliang; Li, Jing; Zhang, Yong; Gao, Ming-Qing

    2016-01-01

    Fibroblasts are predominant components of mammary stromal cells and play crucial roles in the development and involution of bovine mammary gland; however, whether these cells contribute to mastitis has not been demonstrated. Thus, we have undertaken biological and molecular characterization of inflammation-associated fibroblasts (INFs) extracted from bovine mammary glands with clinical mastitis and normal fibroblasts (NFs) from slaughtered dairy cows because of fractured legs during lactation. The functional contributions of INFs to normal epithelial cells were also investigated by using an in vitro co-culture model. We present evidence that the INFs were activated fibroblasts and showed inflammation-related features. Moreover, INFs significantly inhibited the proliferation and β-casein secretion of epithelial cells, as well as upregulated the expression of tumor necrosis factor-α and interleukin-8 in epithelial cells. These findings indicate that functional alterations can occur in stromal fibroblasts within the bovine mammary gland during mastitis, demonstrating the importance of stromal fibroblasts in bovine mastitis and its treatment. PMID:27272504

  6. Mammary Gland Involution Provides a Unique Model to Study the TGF-β Cancer Paradox

    PubMed Central

    Guo, Qiuchen; Betts, Courtney; Pennock, Nathan; Mitchell, Elizabeth; Schedin, Pepper

    2017-01-01

    Transforming Growth Factor-β (TGF-β) signaling in cancer has been termed the “TGF-β paradox”, acting as both a tumor suppresser and promoter. The complexity of TGF-β signaling within the tumor is context dependent, and greatly impacted by cellular crosstalk between TGF-β responsive cells in the microenvironment including adjacent epithelial, endothelial, mesenchymal, and hematopoietic cells. Here we utilize normal, weaning-induced mammary gland involution as a tissue microenvironment model to study the complexity of TGF-β function. This article reviews facets of mammary gland involution that are TGF-β regulated, namely mammary epithelial cell death, immune activation, and extracellular matrix remodeling. We outline how distinct cellular responses and crosstalk between cell types during physiologically normal mammary gland involution contribute to simultaneous tumor suppressive and promotional microenvironments. We also highlight alternatives to direct TGF-β blocking anti-cancer therapies with an emphasis on eliciting concerted microenvironmental-mediated tumor suppression. PMID:28098775

  7. Stromal fibroblasts derived from mammary gland of bovine with mastitis display inflammation-specific changes.

    PubMed

    Chen, Qing; He, Guiliang; Zhang, Wenyao; Xu, Tong; Qi, Hongliang; Li, Jing; Zhang, Yong; Gao, Ming-Qing

    2016-06-07

    Fibroblasts are predominant components of mammary stromal cells and play crucial roles in the development and involution of bovine mammary gland; however, whether these cells contribute to mastitis has not been demonstrated. Thus, we have undertaken biological and molecular characterization of inflammation-associated fibroblasts (INFs) extracted from bovine mammary glands with clinical mastitis and normal fibroblasts (NFs) from slaughtered dairy cows because of fractured legs during lactation. The functional contributions of INFs to normal epithelial cells were also investigated by using an in vitro co-culture model. We present evidence that the INFs were activated fibroblasts and showed inflammation-related features. Moreover, INFs significantly inhibited the proliferation and β-casein secretion of epithelial cells, as well as upregulated the expression of tumor necrosis factor-α and interleukin-8 in epithelial cells. These findings indicate that functional alterations can occur in stromal fibroblasts within the bovine mammary gland during mastitis, demonstrating the importance of stromal fibroblasts in bovine mastitis and its treatment.

  8. Discovery of Novel Mammary Developmental and Cancer Genes Using ENU Mutagenesis

    DTIC Science & Technology

    2002-10-01

    death rates we need new therapeutic targets, currently a major challenge facing cancer researchers This requires an understanding of the undiscovered pathways that operate to drive breast cancer cell proliferation, cell survival and cell differentiation, pathways which are also likely to operate during normal mammary development, and which go awry in cancer The discovery of signalling pathways operative in breast cancer has utilised examination of mammary gland development following systemic endocrine ablation or viral insertion, positional cloning in affected families and

  9. Expression of truncated Int6/eIF3e in mammary alveolar epithelium leads to persistent hyperplasia and tumorigenesis

    PubMed Central

    Mack, David L; Boulanger, Corinne A; Callahan, Robert; Smith, Gilbert H

    2007-01-01

    Introduction Int6 has been shown to be an interactive participant with the protein translation initiation complex eIF3, the COP9 signalosome and the regulatory lid of the 26S proteasome. Insertion of mouse mammary tumor virus into the Int6 locus creates a C-terminally truncated form of the protein. Expression of the truncated form of Int6 (Int6sh) in stably transfected human and mouse mammary epithelial cell lines leads to cellular transformation. In addition, decreased expression of Int6/eIF3e is observed in approximately one third of all human breast carcinomas. Methods To validate that Int6sh has transforming activity in vivo, a transgenic mouse model was designed using the whey acidic protein (Wap) promoter to target expression of truncated Int6 to differentiating alveolar epithelial cells in the mammary gland. Microarray analyses were performed on normal, premalignant and malignant WapInt6sh expressing tissues. Results Mammary tumors developed in 42% of WapInt6sh heterozygous parous females at an average age of 18 months. In WapInt6sh mice, the contralateral mammary glands from both tumorous and non-tumorous tissues contained widespread focal alveolar hyperplasia. Only 4% of WapInt6sh non-breeding females developed tumors by 2 years of age. The Wap promoter is active only during estrus in the mammary tissue of cycling non-pregnant mice. Microarray analyses of mammary tissues demonstrated that Int6sh expression in the alveolar tissue altered the mammary transcriptome in a specific manner that was detectable even in the first pregnancy. This Int6sh-specific transcriptome pattern subsequently persisted in both the Int6sh-expressing alveolar hyperplasia and mammary tumors. These observations are consistent with the conclusion that WapInt6sh-expressing alveolar cells survive involution following the cessation of lactation, and subsequently give rise to the mammary tumors that arise in aging multiparous females. Conclusion These observations provide direct in vivo

  10. Calmodulin-mediated activation of Akt regulates survival of c-Myc-overexpressing mouse mammary carcinoma cells.

    PubMed

    Deb, Tushar B; Coticchia, Christine M; Dickson, Robert B

    2004-09-10

    c-Myc-overexpressing mammary epithelial cells are proapoptotic; their survival is strongly promoted by epidermal growth factor (EGF). We now demonstrate that EGF-induced Akt activation and survival in transgenic mouse mammary tumor virus-c-Myc mouse mammary carcinoma cells are both calcium/calmodulin-dependent. Akt activation is abolished by the phospholipase C-gamma inhibitor U-73122, by the intracellular calcium chelator BAPTA-AM, and by the specific calmodulin antagonist W-7. These results implicate calcium/calmodulin in the activation of Akt in these cells. In addition, Akt activation by serum and insulin is also inhibited by W-7. EGF-induced and calcium/calmodulin-mediated Akt activation occurs in both tumorigenic and non-tumorigenic mouse and human mammary epithelial cells, independent of their overexpression of c-Myc. These results imply that calcium/calmodulin may be a common regulator of Akt activation, irrespective of upstream receptor activator, mammalian species, and transformation status in mammary epithelial cells. However, only c-Myc-overexpressing mouse mammary carcinoma cells (but not normal mouse mammary epithelial cells) undergo apoptosis in the presence of the calmodulin antagonist W-7, indicating the vital selective role of calmodulin for survival of these cells. Calcium/calmodulin-regulated Akt activation is mediated directly by neither calmodulin kinases nor phosphatidylinositol 3-kinase (PI-3 kinase). Pharmacological inhibitors of calmodulin kinase kinase and calmodulin kinases II and III do not inhibit EGF-induced Akt activation, and calmodulin antagonist W-7 does not inhibit phosphotyrosine-associated PI-3 kinase activation. Akt is, however, co-immunoprecipitated with calmodulin in an EGF-dependent manner, which is inhibited by calmodulin antagonist W-7. We conclude that calmodulin may serve a vital regulatory function to direct the localization of Akt to the plasma membrane for its activation by PI-3 kinase.

  11. Effect of DETA-NONOate and papaverine on vasodilation of human internal mammary artery.

    PubMed

    Rahimi, Nastaran; Dehpour, Ahmad R; Javadi-Paydar, Mehrak; Sohanaki, Hamid; Rabbani, Shahram; Ansari, Mohammad; Tafti, Seyed Hossein Ahmadi

    2011-12-01

    In this study, the relaxatory effect of DETA-NONOate is compared with that of papaverine on isolated human internal mammary artery. We investigated the inhibitory effects of DETA-NONOate and papaverine on phenylephrine-induced contractile response in internal mammary artery segments. The internal mammary artery segments, taken from methodologically matched patients who underwent coronary artery bypass grafting, were prepared, placed in an organ bath, and contracted with phenylephrine (10(-9) to 10(-4) mol/L) to investigate their relaxatory response to DETA-NONOate or papaverine. Phenylephrine dose-response contraction was obtained after 1, 2, and 3 h in segments pre-incubated with DETA-NONOate or papaverine for 30 min. The EC50 that presented for internal mammary artery segments incubated with DETA-NONOate was 3.523 ± 1.2696 × 10(-7) mol/L, and for papaverine was 3.467 ± 1.2145 × 10(-6) mol/L. In segments pre-incubated with DETA-NONOate, the contractile response to phenylephrine was suppressed in the first 2 h post-incubation, compared with control responsive groups (p < 0.05), but this inhibition was revoked after 3 h post-incubation. We showed that DETA-NONOate has a more significant relaxative effect by comparison with papaverine; moreover, continuous and long-lasting nitric oxide production by DETA-NONOate might be of great importance for the outcome from coronary artery bypass grafting, when internal mammary artery is used as a conduit.

  12. Duodenal infusions of palmitic, stearic or oleic acids differently affect mammary gland metabolism of fatty acids in lactating dairy cows.

    PubMed

    Enjalbert, F; Nicot, M C; Bayourthe, C; Moncoulon, R

    1998-09-01

    The effect of dietary lipids on the fatty acid (FA) profile of cows' milk fat is mainly dependent on digestive processes and mammary gland uptake and metabolism of FA. The objective of this study was to determine the separate effects of high arterial concentrations of 16:0, 18:0 and cis-18:1(n-9) on uptake, synthesis and 18:0 desaturation rate in the mammary gland of lactating dairy cows, via arterio-venous differences and mammary gland balance of FA. In a 4 x 4 Latin square, four lactating Holstein cows with cannula in the proximal duodenum were infused duodenally with a mixture providing daily 0 (C treatment) or 500 g FA with mainly 16:0 (P treatment), 18:0 (S treatment) or cis-18:1(n-9) (O treatment). Significantly higher arterial concentrations of infused FA in arterial plasma nonesterified FA and triglycerides (NETGFA) were observed with P and O treatments, but the effect of the S treatment was much lower. Arterio-venous differences of NETGFA increased with arterial concentrations. The number of synthesized FA in the mammary gland was not significantly affected by duodenal infusion of FA. Mean chain length was significantly reduced by P and O treatments, suggesting an effect of mammary gland uptake of long-chain FA on the termination process of mammary gland synthesis of FA. Across all treatments, 4:0 mammary gland balance increased linearly (r = 0.67, P = 0.004) with mammary gland FA uptake. Mammary gland desaturation of 18:0 to cis-18:1(n-9) averaged 52% and was not significantly affected by treatments, but was reduced by trans-18:1 mammary gland uptake. Uptake, synthesis and desaturation of FA by the mammary gland of dairy cows are affected by arterial concentrations of 16:0, 18:0 and cis-18:1(n-9).

  13. Evaluation of clinical breast examination and breast ultrasonography among pregnant women in Abakaliki, Nigeria

    PubMed Central

    Ezeonu, Paul Olisaemeka; Ajah, Leonard Ogbonna; Onoh, Robinson Chukwudi; Lawani, Lucky Osaheni; Enemuo, Vincent Chidi; Agwu, Uzoma MaryRose

    2015-01-01

    Background Breast cancer in pregnancy accounts for 2%–3% of all breast cancers. The increased vascularity and lymphatic drainage from the breast during pregnancy potentiate the metastatic spread of the cancer to the regional lymph nodes. However, the increased breast density in pregnancy makes it difficult to detect breast lesions early. Aim To evaluate and compare the detection rate of breast lesions using clinical breast examination (CBE) and breast ultrasonography among pregnant women. Methodology A cross-sectional comparative study involving antenatal clinic attendees at the Federal Teaching Hospital, Abakaliki, was conducted between March 3, 2014, and December 31, 2014. CBE and breast ultrasonography were done in the participants at booking and repeated at 6 weeks postpartum. Fine-needle aspiration cytology and histology were done in women with suspicious breast lesions on CBE or breast ultrasonography or both. Data analysis was both descriptive and inferential at the 95% confidence level using the Statistical Package for the Social Sciences (SPSS) software version 17.0. Test of significance was done using chi-square test. A P-value of less than or equal to 0.05 was considered statistically significant. Results A total of 320 pregnant women participated in the study. Of these, 267 (83.4%) were aware of breast cancer. Although more lesions were detected with breast ultrasonography than by CBE, there was no statistically significant difference between them (25 versus 17; P=0.26). The histology of the lesions revealed 21 benign lesions and 4 normal breast tissues. The sensitivity of breast ultrasonography was 95.2%, while that of CBE was 66.7%. The specificity, positive predictive value, and negative predictive value were similar between CBE and breast ultrasonography. Conclusion The detection rates of breast lesions by both CBE and breast ultrasonography were equivalent during pregnancy and 6 weeks postpartum, making CBE a convenient and very cost

  14. Follow-up of renal and mesenteric artery revascularization with duplex ultrasonography

    PubMed Central

    Taylor, David C.; Houston, Gordon T.M.; Anderson, Caroline; Jameson, Margot; Popatia, Shelley

    1996-01-01

    Objective To evaluate the long-term anatomic results of renal revascularization procedures using duplex ultrasonography. Design A case series. Setting A university-affiliated hospital. Patients Twenty-five patients who had undergone renal percutaneous transluminal angioplasty (PTA) (18 arteries), renal bypass (10 arteries) and mesenteric bypass (6 arteries). The mean follow-up was 22 months (range from 3 to 48 months) for those who underwent renal PTA, 23 months (range from 1.5 to 70 months) for those who underwent renal bypass and 34 months (range from 8 to 144 months) for those who underwent mesenteric bypass. Main Outcome Measures Patency rates for the three procedures as assessed by duplex ultrasonography. Results Duplex ultrasonography demonstrated patency without stenosis after renal and mesenteric artery revascularization in 14 arteries subjected to renal PTA, 9 arteries subjected to renal bypass and 6 arteries subjected to mesenteric bypass. Three arteries that had renal PTA had recurrent vessel stenosis and one had occlusion. One artery that had renal bypass showed occlusion. Conclusions Renal PTA, renal bypass and mesenteric bypass are durable procedures at 2 years of follow-up, and duplex ultrasonography is a valuable method for assessing the patency of arteries after renal and mesenteric revascularization. PMID:8599785

  15. Prevention of Human Mammary Carcinogenesis

    DTIC Science & Technology

    1995-06-30

    selected naturally-occurring agents (-)- epigallocatechin gallate ( EGCG ), indole-3-carbinol (13C) and genistein (GEN) for growth inhibition of 184-B5...mechanisms of BP-induced and GEN-induced alterations in cell cycle are being investigated in the ongoing studies. In addition, effects of 13C and EGCG are...rodent mammary tumorigenesis. The maximally nontoxic doses of EGCG , 13C and GEN identified by initial dose-response experiments, were used. The data

  16. Isoenzymes of protein kinase C in rat mammary tissue: changes in properties and relative amounts during pregnancy and lactation.

    PubMed

    Connor, K; Clegg, R A

    1993-05-01

    Protein kinase isoenzymes belonging to the protein kinase C (PK-C) family present in rat mammary tissue have been resolved from one another by chromatography on hydroxyapatite, and characterized. PK-C alpha is the predominant isoenzyme and is present at a constant level of activity throughout mammary-gland development and differentiation. In contrast, marked changes in the relative abundance of other mammary PK-C isoenzymes accompany the transition from pregnancy to lactation. The sensitivity of mammary PK-C alpha to Ca2+ is greater in tissue from pregnant than from lactating rats. This isoenzyme has other atypical properties consistent with its being more highly phosphorylated than PK-C alpha in rat brain and spleen. One of the protein kinase isoenzymes resolved from mammary tissue recognizes the peptide substrate used to assay AMP-activated kinase and may thus interfere in the determination of this activity. Another is fully active in the absence of Ca2+ and is more than 80% active in the absence of added lipid effectors. A 'housekeeping' role is proposed for PK-C alpha in mammary tissue, whereas the less abundant PK-C isoenzymes may be involved in mammary cell proliferation and differentiation.

  17. Increased levels of interleukins 8 and 10 as findings of canine inflammatory mammary cancer.

    PubMed

    de Andrés, Paloma Jimena; Illera, Juan Carlos; Cáceres, Sara; Díez, Lucía; Pérez-Alenza, Maria Dolores; Peña, Laura

    2013-04-15

    Inflammatory mammary cancer (IMC) is a distinct form of mammary cancer that affects dogs and women [in humans, IMC is known as inflammatory breast cancer (IBC)], and is characterized by a sudden onset and an aggressive clinical course. Spontaneous canine IMC shares epidemiologic, histopathological and clinical characteristics with the disease in humans and has been proposed as the best spontaneous animal model for studying IBC, although several aspects remain unstudied. Interleukins (ILs) play an important role in cancer as potential modulators of angiogenesis, leukocyte infiltration and tumor growth. The aims of the present study were to assess serum and tumor levels of several ILs (IL-1α, IL-1β, IL-6, IL-8 and IL-10) by enzyme-immunoassay in dogs bearing benign and malignant mammary tumors, including dogs with IMC, for a better understanding of this disease. Forty-eight dogs were prospectively included. Animals consisted of 7 healthy Beagles used as donors for normal mammary glands (NMG) and serum controls (SCs), 10 dogs with hyperplasias and benign mammary tumors (HBMT), 24 with non-inflammatory malignant mammary tumors (non-IMC MMT) and 7 dogs with clinical and pathological IMC. IL-8 (serum) and IL-10 (serum and tissue homogenate) levels were higher in the dogs with IMC compared with the non-IMC MMT group. ILs were increased with tumor malignancy as follows: in tumor homogenates IL-6 levels were higher in malignant tumors (IMC and non-IMC MMT) versus HBMT and versus NMG and tumor IL-8 was increased in malignant tumors versus NMG; in serum, IL-1α and IL-8 levels were higher in the malignant groups respect to HBMT and SCs; interestingly, IL-10 was elevated only in the serum of IMC animals. To the best of our knowledge, this is the first report that analyzes ILs in IMC and IL-10 in canine mammary tumors. Our results indicate a role for IL-6, IL-8 and IL-10 in canine mammary malignancy and specific differences in ILs content in IMC versus non-IMC MMT that could

  18. Canine mammary tumors as a model for human disease.

    PubMed

    Abdelmegeed, Somaia M; Mohammed, Sulma

    2018-06-01

    Animal models for examining human breast cancer (HBC) carcinogenesis have been extensively studied and proposed. With the recent advent of immunotherapy, significant attention has been focused on the dog as a model for human cancer. Dogs develop mammary tumors and other cancer types spontaneously with an intact immune system, which exhibit a number of clinical and molecular similarities to HBC. In addition to the spontaneous tumor presentation, the clinical similarities between human and canine mammary tumors (CMT) include the age at onset, hormonal etiology and course of the diseases. Furthermore, factors that affect the disease outcome, including tumor size, stage and lymph node invasion, are similar in HBC and CMT. Similarly, the molecular characteristics of steroid receptor, epidermal growth factor, proliferation marker, metalloproteinase and cyclooxygenase expression, and the mutation of the p53 tumor suppressor gene in CMT, mimic HBC. Furthermore, ductal carcinomas in situ in human and canine mammary glands are particularly similar in their pathological, molecular and visual characteristics. These CMT characteristics and their similarities to HBC indicate that the dog could be an excellent model for the study of human disease. These similarities are discussed in detail in the present review, and are compared with the in vitro and other in vivo animal models available.

  19. Reconstruction of Mammary Gland Structure Using Three-Dimensional Computer-Based Microscopy

    DTIC Science & Technology

    2001-08-01

    Segmentation of Mammary Gland Ductal Structure Using Geometric Methods. P.l.’s Malladi R . and Ortiz de Solorzano C. Submitted to the LBNL Laboratory...mammary gland biology". Fernandez-Gonzalez, R ., Jones A., Garcia-Rodriguez E., Knowles D., Sudar D. Ortiz de Solorzano, C. Proceedings of Microscopy...the text. 25 3DRcn4rclr FieC4 eto m oosOtosMCUCP suto 5 2 3p4 eto 6 ’lw r 26o W ~Fl. Case Section Area Tools Opt~ons Micoscope

  20. A Study of Using Massage Therapy Accompanied with Stretching Exercise for Rehabilitation of Mammary Gland Hyperplasia.

    PubMed

    Lv, Pin; Chong, Yuping; Zou, Huagang; Chen, Xiangxian

    2016-01-01

    To apply massage therapy accompanied with stretching exercises for treatment of mammary gland hyperplasia, evaluate the clinical outcome in patients, and estimate the therapy as a novel treatment method for mammary hyperplasia. 28 adult female patients were selected and treated with massage therapy and stretching exercises focusing on skeleton muscles of chest, abdomen, and axilla. The mammary gland oxyhemoglobin (OxyHb) and deoxyhemoglobin (DeoxyHb) levels were detected before and after treatment after 15, 30, and 45 days. In this cohort, pretreatment OxyHb (mean ± SD) is 1.32 ± 0.14 (medium-high), and DeoxyHb is 0.87 ± 0.13 (normal). All patients were clinically diagnosed with benign mammary gland hyperplasia and mastitis. The posttreatment OxyHb levels are 1.23 ± 0.09 (normal-medium, 15-day), 1.16 ± 0.08 (normal, 30-day), and 1.05 ± 0.04 (normal, 45-day), and DeoxyHb levels are 0.90 ± 0.11 (normal, 15-day), 0.94 ± 0.18 (normal, 30-day), and 0.98 ± 0.12 (normal, 45-day). Patients were diagnosed with decreased hyperplasia 15 and 30 days after treatment and with no symptom of hyperplasia in mammary gland 45 days after treatment. Mammary gland hyperplasia is closely correlated with pathological changes of skeletal muscles and could be significantly improved by massage therapy and stretching exercises targeting neighboring skeletal muscles.

  1. Validation of ultrasonography of the thyroid gland for epidemiological purposes.

    PubMed

    Knudsen, N; Bols, B; Bülow, I; Jørgensen, T; Perrild, H; Ovesen, L; Laurberg, P

    1999-11-01

    Ultrasonography of the thyroid is often used in epidemiological surveys, thus thorough characterization of the interobserver variation of the different parameters obtained is important. Various methods have been used for measuring thyroid volume, and different formulas have been used for calculation of thyroid volume from the measured dimensions. In this article, two principles of thyroid volume measurement are described in detail: the wellknown method based on the three axes of each lobe and a new principle based on planimetry in two planes. The interobserver variation of the examination and the measuring procedure in itself were tested on 25 participants in a population study. A comparison of postmortem ultrasonography of the thyroid and results of an autopsy was performed. Good correlation and agreement between observers was found for thyroid volume (r = 0.98) and prevalence of thyroid nodules (kappa = 0.72), whereas echogenecity and echopattern showed little agreement. The correlation of thyroid volume by ultrasonography to autopsy results was satisfactory (r = 0.93), but the volume tended to be slightly underestimated even when using the formula pi/6(= 0.52)*length*width*depth. No major differences were found between the performance of the two principles of volume calculation. We conclude that when the measuring procedure is well defined, results of ultrasonography are comparable between observers for thyroid volume and prevalence of thyroid nodules, but not for echogenecity or echopattern. The formula of length*depth*width*pi/6 is suitable for thyroid volume measurement.

  2. Portable ultrasonography in mass casualty incidents: The CAVEAT examination.

    PubMed

    Stawicki, Stanislaw Peter; Howard, James M; Pryor, John P; Bahner, David P; Whitmill, Melissa L; Dean, Anthony J

    2010-11-18

    Ultrasonography used by practicing clinicians has been shown to be of utility in the evaluation of time-sensitive and critical illnesses in a range of environments, including pre-hospital triage, emergency department, and critical care settings. The increasing availability of light-weight, robust, user-friendly, and low-cost portable ultrasound equipment is particularly suited for use in the physically and temporally challenging environment of a multiple casualty incident (MCI). Currently established ultrasound applications used to identify potentially lethal thoracic or abdominal conditions offer a base upon which rapid, focused protocols using hand-carried emergency ultrasonography could be developed. Following a detailed review of the current use of portable ultrasonography in military and civilian MCI settings, we propose a protocol for sonographic evaluation of the chest, abdomen, vena cava, and extremities for acute triage. The protocol is two-tiered, based on the urgency and technical difficulty of the sonographic examination. In addition to utilization of well-established bedside abdominal and thoracic sonography applications, this protocol incorporates extremity assessment for long-bone fractures. Studies of the proposed protocol will need to be conducted to determine its utility in simulated and actual MCI settings.

  3. Ultrasonography of the equine shoulder: technique and normal appearance.

    PubMed

    Tnibar, M A; Auer, J A; Bakkali, S

    1999-01-01

    This study was intended to document normal ultrasonographic appearance of the equine shoulder and anatomic landmarks useful in clinical imaging. Both forelimbs of five equine cadavers and both forelimbs of six live adult horses were used. To facilitate understanding of the images, a zoning system assigned to the biceps brachii and to the infraspinatus tendon was developed. Ultrasonography was performed with a real-time B-mode semiportable sector scanner using 7.5- and 5-MHz transducers. On one cadaver limb, magnetic resonance imaging (MRI) was performed using a system at 1.5 Tesla, T1-weighted spin-echo sequence. Ultrasonography images were compared to frozen specimens and MRI images to correlate the ultrasonographic findings to the gross anatomy of the shoulder. Ultrasonography allowed easy evaluation of the biceps brachii and the infraspinatus tendon and their bursae, the supraspinatus muscle and tendons, the superficial muscles of the shoulder, and the underlying humerus and scapula. Only the lateral and, partially, the caudal aspects of the humeral head could be visualized with ultrasound. Ultrasonographic appearance, orientation, and anatomic relationships of these structures are described. Ultrasonographic findings correlated well with MRI images and with gross anatomy in the cadavers' limbs.

  4. Protein quality and quantity and insulin control of mammary gland glucose utilization during lactation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Masor, M.L.

    1987-01-01

    Virgin Sprague-Dawley rats were bred, and fed laboratory stock (STOCK), 13% casein plus methionine, 13% wheat gluten, or 5% casein plus methionine through gestation and 4 days of lactation. Diets were switched at parturition to determine the effects of dietary protein quality and quantity fed during gestation and/or lactation on insulin stimulation of mammary glucose utilization. On day 20 of gestation (20G) and day 4 of lactation (4L) the right inguinal-abdominal mammary glands were removed, and acini and tissue slices were incubated in Krebs buffer with or without insulin containing (U-/sup 14/C)-glucose and 5mM glucose for 1 hour at 37/degrees/C.more » Glucose incorporation into CO/sub 2/, lipid and lactose was determined. Glucose incorporation into CO/sub 2/ and lipid, but not lactose was stimulated by insulin in mammary slices. Diet effects on glucose utilization in acini were confirmed in slices for basal and insulin stimulated levels. Treatment affected the absolute increase of insulin stimulation. Regression analysis significantly correlated pup weight gain with total glucose utilization. Poor dietary protein quality and quantity fed during gestation impaired both overall response of mammary glucose utilization to insulin stimulation, and mammary development during pregnancy. Improving protein value at parturition did not overcome those deficits by 4L.« less

  5. Epithelial Xbp1 Is Required for Cellular Proliferation and Differentiation during Mammary Gland Development

    PubMed Central

    Hasegawa, Daisuke; Calvo, Veronica; Avivar-Valderas, Alvaro; Lade, Abigale; Chou, Hsin-I; Lee, Youngmin A.; Farias, Eduardo F.; Aguirre-Ghiso, Julio A.

    2015-01-01

    Xbp1, a key mediator of the unfolded protein response (UPR), is activated by IRE1α-mediated splicing, which results in a frameshift to encode a protein with transcriptional activity. However, the direct function of Xbp1 in epithelial cells during mammary gland development is unknown. Here we report that the loss of Xbp1 in the mammary epithelium through targeted deletion leads to poor branching morphogenesis, impaired terminal end bud formation, and spontaneous stromal fibrosis during the adult virgin period. Additionally, epithelial Xbp1 deletion induces endoplasmic reticulum (ER) stress in the epithelium and dramatically inhibits epithelial proliferation and differentiation during lactation. The synthesis of milk and its major components, α/β-casein and whey acidic protein (WAP), is significantly reduced due to decreased prolactin receptor (Prlr) and ErbB4 expression in Xbp1-deficient mammary epithelium. Reduction of Prlr and ErbB4 expression and their diminished availability at the cell surface lead to reduced phosphorylated Stat5, an essential regulator of cell proliferation and differentiation during lactation. As a result, lactating mammary glands in these mice produce less milk protein, leading to poor pup growth and postnatal death. These findings suggest that the loss of Xbp1 induces a terminal UPR which blocks proliferation and differentiation during mammary gland development. PMID:25713103

  6. The mouse mammary gland as a sentinel organ: distinguishing 'control' populations with diverse environmental histories.

    PubMed

    Kolla, SriDurgaDevi; Pokharel, Aastha; Vandenberg, Laura N

    2017-03-09

    There are numerous examples of laboratory animals that were inadvertently exposed to endocrine disrupting chemicals (EDCs) during the process of conducting experiments. Controlling contaminations in the laboratory is challenging, especially when their source is unknown. Unfortunately, EDC contaminations can interfere with the interpretation of data during toxicological evaluations. We propose that the male CD-1 mouse mammary gland is a sensitive bioassay to evaluate the inadvertent contamination of animal colonies. We evaluated mammary glands collected from two CD-1 mouse populations with distinct environmental histories. Population 1 was born and raised in a commercial laboratory with unknown EDC exposures; Population 2 was the second generation raised in an animal facility with limited exposures to xenoestrogens from caging, feed, etc. Mammary glands were collected from all animals and evaluated using morphometric techniques to quantify morphological characteristics of the mammary gland. Population 1 (with suspected history of environmental chemical exposure) and Population 2 (with known limited history of xenoestrogen exposure) were morphologically distinguishable in adult males, prepubertal females, and pubertal females. Mammary glands from males raised in the commercial animal facility were significantly more developed, with larger ductal trees and more branching points. The appearance of these mammary glands was consistent with prior reports of male mice exposed to low doses of bisphenol A (BPA) during early development. In females, the two populations were morphologically distinct at both prepuberty and puberty, with the most striking differences observed in the number, size, and density of terminal end buds, e.g. highly proliferative structures found in the developing mammary gland. Collectively, these results suggest that the mouse mammary gland has the potential to be used as a sentinel organ to evaluate and distinguish animal colonies raised in different

  7. Inhibition of peripubertal sheep mammary gland development by cysteamine through reducing progesterone and growth factor production.

    PubMed

    Zhao, Yong; Feng, Yanni; Zhang, Hongfu; Kou, Xin; Li, Lan; Liu, Xinqi; Zhang, Pengfei; Cui, Liantao; Chu, Meiqiang; Shen, Wei; Min, Lingjiang

    2017-02-01

    Cysteamine has been used for treating cystinosis for many years, and furthermore it has also been used as a therapeutic agent for different diseases including Huntington's disease, Parkinson's disease (PD), nonalcoholic fatty liver disease, malaria, cancer, and others. Although cysteamine has many potential applications, its use may also be problematic. The effects of low doses of cysteamine on the reproductive system, especially the mammary glands are currently unknown. In the current investigation, low dose (10 mg/kg BW/day) of cysteamine did not affect sheep body weight gain or organ index of the liver, spleen, or heart; it did, however, increase the levels of blood lymphocytes, monocytes, and platelets. Most interestingly, it inhibited mammary gland development after 2 or 5 months of treatment by reducing the organ index and the number of mammary gland ducts. Plasma growth hormone and estradiol remained unchanged; however, plasma progesterone levels and the protein level of HSD3β1 in sheep ovaries were decreased by cysteamine. In addition to steroid hormones, growth factors produced in the mammary glands also play crucial roles in mammary gland development. Results showed that protein levels of HGF, GHR, and IGF1R were decreased after 5 months of cysteamine treatment. These findings together suggest that progesterone and local growth factors in mammary glands might be involved in cysteamine initiated inhibition of pubertal ovine mammary gland development. Furthermore, it may lead to a reduction in fertility. Therefore, cysteamine should be used with great caution until its actions have been further investigated and its limitations overcome. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Maternal dioxin exposure combined with a diet high in fat increases mammary cancer incidence in mice.

    PubMed

    La Merrill, Michele; Harper, Rachel; Birnbaum, Linda S; Cardiff, Robert D; Threadgill, David W

    2010-05-01

    RESULTS from previous studies have suggested that breast cancer risk correlates with total lifetime exposure to estrogens and that early-life 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure or diets high in fat can also increase cancer risk. Because both TCDD and diet affect the estrogen pathway, we examined how TCDD and a high-fat diet (HFD) interact to alter breast cancer susceptibility. We exposed pregnant female FVB/NJ mice (12.5 days postcoitus) to 1 microg/kg TCDD or vehicle; at parturition, the dams were randomly assigned to a low-fat diet (LFD) or a high-fat diet (HFD). Female offspring were maintained on the same diets after weaning and were exposed to 7,12-dimethylbenz[a]anthracene on postnatal days (PNDs) 35, 49, and 63 to initiate mammary tumors. A second cohort of females was treated identically until PND35 or PND49, when mammary gland morphology was examined, or PND50, when mammary gland mRNA was analyzed. We found that maternal TCDD exposure doubled mammary tumor incidence only in mice fed the HFD. Among HFD-fed mice, maternal TCDD exposure caused rapid mammary development with increased Cyp1b1 (cytochrome P450 1B1) expression and decreased Comt (catechol-O-methyltransferase) expression in mammary tissue. Maternal TCDD exposure also increased mammary tumor Cyp1b1 expression. Our data suggest that the HFD increases sensitivity to maternal TCDD exposure, resulting in increased breast cancer incidence, by changing metabolism capability. These results provide a mechanism to explain epidemiological data linking early-life TCDD exposure and diets high in fat to increased risk for breast cancer in humans.

  9. Stromal adipocyte enhancer-binding protein (AEBP1) promotes mammary epithelial cell hyperplasia via proinflammatory and hedgehog signaling.

    PubMed

    Holloway, Ryan W; Bogachev, Oleg; Bharadwaj, Alamelu G; McCluskey, Greg D; Majdalawieh, Amin F; Zhang, Lei; Ro, Hyo-Sung

    2012-11-09

    Disruption of mammary stromal-epithelial communication leads to aberrant mammary gland development and induces mammary tumorigenesis. Macrophages have been implicated in carcinogenesis primarily by creating an inflammatory microenvironment, which promotes growth of the adjacent epithelial cells. Adipocyte enhancer-binding protein 1 (AEBP1), a novel proinflammatory mediator, promotes macrophage inflammatory responsiveness by inducing NF-κB activity, which has been implicated in tumor cell growth and survival by aberrant sonic hedgehog (Shh) expression. Here, we show that stromal macrophage AEBP1 overexpression results in precocious alveologenesis in the virgin AEBP1 transgenic (AEBP1(TG)) mice, and the onset of ductal hyperplasia was accelerated in AEBP1(TG) mice fed a high fat diet, which induces endogenous AEBP1 expression. Transplantation of AEBP1(TG) bone marrow cells into non-transgenic (AEBP1(NT)) mice resulted in alveolar hyperplasia with up-regulation of NF-κB activity and TNFα expression as displayed in the AEBP1(TG) mammary macrophages and epithelium. Shh expression was induced in AEBP1(TG) macrophages and RAW264.7 macrophages overexpressing AEBP1. The Shh target genes Gli1 and Bmi1 expression was induced in the AEBP1(TG) mammary epithelium and HC11 mammary epithelial cells co-cultured with AEBP1(TG) peritoneal macrophages. The conditioned AEBP1(TG) macrophage culture media promoted NF-κB activity and survival signal, Akt activation, in HC11 cells, whereas such effects were abolished by TNFα neutralizing antibody treatment. Furthermore, HC11 cells displayed enhanced proliferation in response to AEBP1(TG) macrophages and their conditioned media. Our findings highlight the role of AEBP1 in the signaling pathways regulating the cross-talk between mammary epithelium and stroma that could predispose the mammary tissue to tumorigenesis.

  10. Stromal Adipocyte Enhancer-binding Protein (AEBP1) Promotes Mammary Epithelial Cell Hyperplasia via Proinflammatory and Hedgehog Signaling*

    PubMed Central

    Holloway, Ryan W.; Bogachev, Oleg; Bharadwaj, Alamelu G.; McCluskey, Greg D.; Majdalawieh, Amin F.; Zhang, Lei; Ro, Hyo-Sung

    2012-01-01

    Disruption of mammary stromal-epithelial communication leads to aberrant mammary gland development and induces mammary tumorigenesis. Macrophages have been implicated in carcinogenesis primarily by creating an inflammatory microenvironment, which promotes growth of the adjacent epithelial cells. Adipocyte enhancer-binding protein 1 (AEBP1), a novel proinflammatory mediator, promotes macrophage inflammatory responsiveness by inducing NF-κB activity, which has been implicated in tumor cell growth and survival by aberrant sonic hedgehog (Shh) expression. Here, we show that stromal macrophage AEBP1 overexpression results in precocious alveologenesis in the virgin AEBP1 transgenic (AEBP1TG) mice, and the onset of ductal hyperplasia was accelerated in AEBP1TG mice fed a high fat diet, which induces endogenous AEBP1 expression. Transplantation of AEBP1TG bone marrow cells into non-transgenic (AEBP1NT) mice resulted in alveolar hyperplasia with up-regulation of NF-κB activity and TNFα expression as displayed in the AEBP1TG mammary macrophages and epithelium. Shh expression was induced in AEBP1TG macrophages and RAW264.7 macrophages overexpressing AEBP1. The Shh target genes Gli1 and Bmi1 expression was induced in the AEBP1TG mammary epithelium and HC11 mammary epithelial cells co-cultured with AEBP1TG peritoneal macrophages. The conditioned AEBP1TG macrophage culture media promoted NF-κB activity and survival signal, Akt activation, in HC11 cells, whereas such effects were abolished by TNFα neutralizing antibody treatment. Furthermore, HC11 cells displayed enhanced proliferation in response to AEBP1TG macrophages and their conditioned media. Our findings highlight the role of AEBP1 in the signaling pathways regulating the cross-talk between mammary epithelium and stroma that could predispose the mammary tissue to tumorigenesis. PMID:22995915

  11. [Pancreatic ultrasonography].

    PubMed

    Fernández-Rodríguez, T; Segura-Grau, A; Rodríguez-Lorenzo, A; Segura-Cabral, J M

    2015-04-01

    Despite the recent technological advances in imaging, abdominal ultrasonography continues to be the first diagnostic test indicated in patients with a suspicion of pancreatic disease, due to its safety, accessibility and low cost. It is an essential technique in the study of inflammatory processes, since it not only assesses changes in pancreatic parenchyma, but also gives an indication of the origin (bile or alcoholic). It is also essential in the detection and tracing of possible complications as well as being used as a guide in diagnostic and therapeutic punctures. It is also the first technique used in the study of pancreatic tumors, detecting them with a sensitivity of around 70% and a specificity of 90%. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  12. Infant formula feeding alters the proliferative status of neonatal mammary glands independent of estrogen signaling

    USDA-ARS?s Scientific Manuscript database

    Soy infant formula contains many phytochemicals, including phytoestrogens, which are structurally similar to estradiol (E2). The mammary gland is particularly sensitive to estrogens, and there are concerns that use of soy-based infant formulas may potentially have adverse effects on mammary tissue ...

  13. Morinda citrifolia (Noni) Juice Augments Mammary Gland Differentiation and Reduces Mammary Tumor Growth in Mice Expressing the Unactivated c-erbB2 Transgene.

    PubMed

    Clafshenkel, William P; King, Tracy L; Kotlarczyk, Mary P; Cline, J Mark; Foster, Warren G; Davis, Vicki L; Witt-Enderby, Paula A

    2012-01-01

    Morinda citrifolia (noni) is reported to have many beneficial properties, including on immune, inflammatory, quality of life, and cancer endpoints, but little is known about its ability to prevent or treat breast cancer. To test its anticancer potential, the effects of Tahitian Noni Juice (TNJ) on mammary carcinogenesis were examined in MMTV-neu transgenic mice. Mammary tumor latency, incidence, multiplicity, and metastatic incidence were unaffected by TNJ treatment, which suggests that it would not increase or decrease breast cancer risk in women taking TNJ for its other benefits. However, noni may be useful to enhance treatment responses in women with existing HER2/neu breast cancer since TNJ resulted in significant reductions in tumor weight and volume and in longer tumor doubling times in mice. Remarkably, its ability to inhibit the growth of this aggressive form of cancer occurred with the mouse equivalent of a recommended dose for humans (<3 oz/day). A 30-day treatment with TNJ also induced significant changes in mammary secondary ductule branching and lobuloalveolar development, serum progesterone levels, and estrous cycling. Additional studies investigating TNJ-induced tumor growth suppression and modified reproductive responses are needed to characterize its potential as a CAM therapy for women with and without HER2(+) breast cancer.

  14. Morinda citrifolia (Noni) Juice Augments Mammary Gland Differentiation and Reduces Mammary Tumor Growth in Mice Expressing the Unactivated c-erbB2 Transgene

    PubMed Central

    Clafshenkel, William P.; King, Tracy L.; Kotlarczyk, Mary P.; Cline, J. Mark; Foster, Warren G.; Davis, Vicki L.; Witt-Enderby, Paula A.

    2012-01-01

    Morinda citrifolia (noni) is reported to have many beneficial properties, including on immune, inflammatory, quality of life, and cancer endpoints, but little is known about its ability to prevent or treat breast cancer. To test its anticancer potential, the effects of Tahitian Noni Juice (TNJ) on mammary carcinogenesis were examined in MMTV-neu transgenic mice. Mammary tumor latency, incidence, multiplicity, and metastatic incidence were unaffected by TNJ treatment, which suggests that it would not increase or decrease breast cancer risk in women taking TNJ for its other benefits. However, noni may be useful to enhance treatment responses in women with existing HER2/neu breast cancer since TNJ resulted in significant reductions in tumor weight and volume and in longer tumor doubling times in mice. Remarkably, its ability to inhibit the growth of this aggressive form of cancer occurred with the mouse equivalent of a recommended dose for humans (<3 oz/day). A 30-day treatment with TNJ also induced significant changes in mammary secondary ductule branching and lobuloalveolar development, serum progesterone levels, and estrous cycling. Additional studies investigating TNJ-induced tumor growth suppression and modified reproductive responses are needed to characterize its potential as a CAM therapy for women with and without HER2+ breast cancer. PMID:22619689

  15. Ultrasonography of ovarian hyperandrogenemia

    NASA Astrophysics Data System (ADS)

    Kuzmina, Svetlana A.; Zharkin, Nikolay A.

    2001-05-01

    The method of ultrasonography is high informative and widely used in diagnostics of ovarian hyperandrogenaemia. The majority of authors consider that a hyperplasia of a stroma is the main pathognomonic marker of polycystic ovaries (PCO). Still recently swell of a stroma was valued visually, that had subjective nature. We offer for the first time a way of diagnostics of stromal hyperplasia grounded on measurement of a volume of a stroma and ovary with ultrasound method, calculation of the ratio of a volume of the ovary to a volume of a stroma for every patient.

  16. Real-time tracheal ultrasonography for confirmation of endotracheal tube placement during cardiopulmonary resuscitation.

    PubMed

    Chou, Hao-Chang; Chong, Kah-Meng; Sim, Shyh-Shyong; Ma, Matthew Huei-Ming; Liu, Shih-Hung; Chen, Nai-Chuan; Wu, Meng-Che; Fu, Chia-Ming; Wang, Chih-Hung; Lee, Chien-Chang; Lien, Wan-Ching; Chen, Shyr-Chyr

    2013-12-01

    This study aimed to evaluate the accuracy of tracheal ultrasonography for assessing endotracheal tube position during cardiopulmonary resuscitation (CPR). We performed a prospective observational study of patients undergoing emergency intubation during CPR. Real-time tracheal ultrasonography was performed during the intubation with the transducer placed transversely just above the suprasternal notch, to assess for endotracheal tube positioning and exclude esophageal intubation. The position of trachea was identified by a hyperechoic air-mucosa (A-M) interface with posterior reverberation artifact (comet-tail artifact). The endotracheal tube position was defined as endotracheal if single A-M interface with comet-tail artifact was observed. Endotracheal tube position was defined as intraesophageal if a second A-M interface appeared, suggesting a false second airway (double tract sign). The gold standard of correct endotracheal intubation was the combination of clinical auscultation and quantitative waveform capnography. The main outcome was the accuracy of tracheal ultrasonography in assessing endotracheal tube position during CPR. Among the 89 patients enrolled, 7 (7.8%) had esophageal intubations. The sensitivity, specificity, positive predictive value, and negative predictive value of tracheal ultrasonography were 100% (95% confidence interval [CI]: 94.4-100%), 85.7% (95% CI: 42.0-99.2%), 98.8% (95% CI: 92.5-99.0%) and 100% (95% CI: 54.7-100%), respectively. Positive and negative likelihood ratios were 7.0 (95% CI: 1.1-43.0) and 0.0, respectively. Real-time tracheal ultrasonography is an accurate method for identifying endotracheal tube position during CPR without the need for interruption of chest compression. Tracheal ultrasonography in resuscitation management may serve as a powerful adjunct in trained hands. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  17. Dietary genistein stimulates mammary development in gilts

    USDA-ARS?s Scientific Manuscript database

    The possible role of the phytoestrogen, genistein, on prepubertal development of mammary glands, hormonal status and bone resorption was investigated in gilts. Forty-five gilts were fed a control diet containing soya (CTLS, n = 15), a control diet without soya (CTL0, n = 15) or the CTLS diet supplem...

  18. The CAR agonist TCPOBOP inhibits lipogenesis and promotes fibrosis in the mammary gland of adolescent female mice.

    PubMed

    Xu, Pengfei; Hong, Fan; Wang, Jing; Dai, Shu; Wang, Jialin; Zhai, Yonggong

    2018-06-15

    Constitutive androstane receptor (CAR) is a nuclear receptor that not only regulates drug-metabolizing enzymes but also influences energy metabolism. TC, 1, 4-bis [2-(3, 5-dichloropyridyloxy)] benzene (TCPOBOP) has been shown to inhibit lipogenesis in the liver and adipose tissues. The mammary gland is mainly composed of fat pads and duct systems in adolescent female mice. Here, activation of CAR by TC reduces the mammary gland weight, blocks lipid accumulation by inhibiting lipogenesis and gluconeogenesis, and accelerates collagen formation and fibrosis in the mammary fat pad of adolescent female mice. This information provides a reference for CAR activation, which may affect mammary gland development in adolescent females. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. MMTV insertional mutagenesis identifies genes, gene families and pathways involved in mammary cancer.

    PubMed

    Theodorou, Vassiliki; Kimm, Melanie A; Boer, Mandy; Wessels, Lodewyk; Theelen, Wendy; Jonkers, Jos; Hilkens, John

    2007-06-01

    We performed a high-throughput retroviral insertional mutagenesis screen in mouse mammary tumor virus (MMTV)-induced mammary tumors and identified 33 common insertion sites, of which 17 genes were previously not known to be associated with mammary cancer and 13 had not previously been linked to cancer in general. Although members of the Wnt and fibroblast growth factors (Fgf) families were frequently tagged, our exhaustive screening for MMTV insertion sites uncovered a new repertoire of candidate breast cancer oncogenes. We validated one of these genes, Rspo3, as an oncogene by overexpression in a p53-deficient mammary epithelial cell line. The human orthologs of the candidate oncogenes were frequently deregulated in human breast cancers and associated with several tumor parameters. Computational analysis of all MMTV-tagged genes uncovered specific gene families not previously associated with cancer and showed a significant overrepresentation of protein domains and signaling pathways mainly associated with development and growth factor signaling. Comparison of all tagged genes in MMTV and Moloney murine leukemia virus-induced malignancies showed that both viruses target mostly different genes that act predominantly in distinct pathways.

  20. Mammary candidiasis: A medical condition without scientific evidence?

    PubMed Central

    Jiménez, Esther; Arroyo, Rebeca; Cárdenas, Nivia; Marín, María; Serrano, Pilar; Fernández, Leonides

    2017-01-01

    Many physicians, midwives and lactation consultants still believe that yeasts (particularly Candida spp.) play an important role as an agent of nipple and breast pain despite the absolute absence of scientific proofs to establish such association. In this context, the objective of this study was to investigate the microorganisms involved in sore nipples and/or painful “shooting” breastfeeding by using a variety of microscopy techniques, as well as culture-dependent and–independent identification methods. Initially, 60 women (30 diagnosed as suffering “mammary candidiasis” and 30 with no painful breastfeeding) were recruited to elucidate the role of their pumps on the milk microbial profiles. After realizing the bias introduced by using such devices, manual expression was selected as the collection method for the microbiological analysis of milk samples provided by 529 women with symptoms compatible with “mammary candidiasis”. Nipple swabs and nipple biopsy samples were also collected from the participating women. Results showed that the role played by yeasts in breast and nipple pain is, if any, marginal. In contrast, our results strongly support that coagulase-negative staphylococci and streptococci (mainly from the mitis and salivarius groups) are the agents responsible for such cases. As a consequence, and following the recommendations of the US Library of Medicine for the nomenclature of infectious diseases, the term “mammary candidiasis” or “nipple thrush” should be avoided when referring to such condition and replaced by “subacute mastitis”. PMID:28704470

  1. Prevalence of the Prefoldin Subunit 5 Gene Deletion in Canine Mammary Tumors

    PubMed Central

    Bornemann-Kolatzki, Kirsten; Neumann, Stephan; Escobar, Hugo Murua; Nolte, Ingo; Hammer, Susanne Conradine; Hewicker-Trautwein, Marion; Junginger, Johannes; Kaup, Franz-Josef; Brenig, Bertram; Schütz, Ekkehard

    2015-01-01

    Background A somatic deletion at the proximal end of canine chromosome 27 (CFA27) was recently reported in 50% of malignant mammary tumors. This region harbours the tumor suppressor gene prefoldin subunit 5 (PFDN5) and the deletion correlated with a higher Ki-67 score. PFDN5 has been described to repress c-MYC and is, therefore, a candidate tumor-suppressor and cancer-driver gene in canine mammary cancer. Aim of this study was to confirm the recurrent deletion in a larger number of tumors. Methods Droplet digital PCR for PFDN5 was performed in DNA from 102 malignant, 40 benign mammary tumors/dysplasias, 11 non-neoplastic mammary tissues and each corresponding genomic DNA from leukocytes. The copy number of PFDN5 was normalized to a reference amplicon on canine chromosome 32 (CFA32). Z-scores were calculated, based on Gaussian distributed normalized PFDN5 copy numbers of the leukocyte DNA. Z-scores ≤ -3.0 in tissue were considered as being indicative of the PFDN5 deletion and called as such. The Ki-67 proliferation index was assessed in a subset of 79 tissue samples by immunohistochemistry. Results The deletion was confirmed in 24% of all malignant tumors, detected in only 7.5% of the benign tumors and was not present in any normal mammary tissue sample. The subgroup of solid carcinomas (n = 9) showed the highest frequency of the deletion (67%) and those malignomas without microscopical high fraction of benign tissue (n = 71) had a 32% frequency (p<0.01 vs. benign samples). The Ki-67 score was found to be significantly higher (p<0.05) in the PFDN5-deleted group compared to malignant tumors without the deletion. Conclusions A somatic deletion of the PFDN5 gene is recurrently present in canine mammary cancer, supporting a potential role in carcinogenesis. The association of this deletion with higher Ki-67 indicates an increased proliferation rate and thus a link to tumor aggressiveness can be hypothesized. The confirmation of earlier results warrants further studies

  2. Role of peptidylarginine deiminase 2 (PAD2) in mammary carcinoma cell migration.

    PubMed

    Horibata, Sachi; Rogers, Katherine E; Sadegh, David; Anguish, Lynne J; McElwee, John L; Shah, Pragya; Thompson, Paul R; Coonrod, Scott A

    2017-05-26

    Penetration of the mammary gland basement membrane by cancer cells is a crucial first step in tumor invasion. Using a mouse model of ductal carcinoma in situ, we previously found that inhibition of peptidylarginine deiminase 2 (PAD2, aka PADI2) activity appears to maintain basement membrane integrity in xenograft tumors. The goal of this investigation was to gain insight into the mechanisms by which PAD2 mediates this process. For our study, we modulated PAD2 activity in mammary ductal carcinoma cells by lentiviral shRNA-mediated depletion, lentiviral-mediated PAD2 overexpression, or PAD inhibition and explored the effects of these treatments on changes in cell migration and cell morphology. We also used these PAD2-modulated cells to test whether PAD2 may be required for EGF-induced cell migration. To determine how PAD2 might promote tumor cell migration in vivo, we tested the effects of PAD2 inhibition on the expression of several cell migration mediators in MCF10DCIS.com xenograft tumors. In addition, we tested the effect of PAD2 inhibition on EGF-induced ductal invasion and elongation in primary mouse mammary organoids. Lastly, using a transgenic mouse model, we investigated the effects of PAD2 overexpression on mammary gland development. Our results indicate that PAD2 depletion or inhibition suppresses cell migration and alters the morphology of MCF10DCIS.com cells. In addition, we found that PAD2 depletion suppresses the expression of the cytoskeletal regulatory proteins RhoA, Rac1, and Cdc42 and also promotes a mesenchymal to epithelial-like transition in tumor cells with an associated increase in the cell adhesion marker, E-cadherin. Our mammary gland organoid study found that inhibition of PAD2 activity suppresses EGF-induced ductal invasion. In vivo, we found that PAD2 overexpression causes hyperbranching in the developing mammary gland. Together, these results suggest that PAD2 plays a critical role in breast cancer cell migration. Our findings that EGF

  3. Development of mammary hyperplasia, dysplasia, and invasive ductal carcinoma in transgenic mice expressing the 8p11 amplicon oncogene NSD3

    PubMed Central

    Turner-Ivey, Brittany; Smith, Ericka L.; Rutkovsky, Alex C.; Spruill, Laura S.; Mills, Jamie N.

    2018-01-01

    Purpose NSD3 has been implicated as a candidate driver oncogene from the 8p11-p12 locus, and we have previously published evidence for its amplification and overexpression in human breast cancer. This aim of this study was to further characterize the transforming function of NSD3 in vivo. Methods We generated a transgenic mouse model in which NSD3 gene expression was driven by the MMTV promoter and expressed in mammary epithelium of FVB mice. Mammary glands were fixed and whole mounts were stained with carmine to visualize gland structure. Mammary tumors were formalin-fixed, and paraffin embedded (FFPE) tumors were stained with hematoxylin and eosin. Results Pups born to transgenic females were significantly underdeveloped compared to pups born to WT females due to a lactation defect in transgenic female mice. Whole mount analysis of the mammary glands of transgenic female mice revealed a profound defect in functional differentiation of mammary gland alveoli that resulted in the lactation defect. We followed parous and virgin NSD3 transgenic and control mice to 50 weeks of age and observed that several NSD3 parous females developed mammary tumors. Whole mount analysis of the mammary glands of tumor-bearing mice revealed numerous areas of mammary hyperplasia and ductal dysplasia. Histological analysis showed that mammary tumors were high-grade ductal carcinomas, and lesions present in other mammary glands exhibited features of alveolar hyperplasia, ductal dysplasia, and carcinoma in situ. Conclusions Our results are consistent with our previous studies and demonstrate that NSD3 is a transforming breast cancer oncogene. PMID:28484924

  4. Hierarchy within the mammary STAT5-driven Wap super-enhancer.

    PubMed

    Shin, Ha Youn; Willi, Michaela; HyunYoo, Kyung; Zeng, Xianke; Wang, Chaochen; Metser, Gil; Hennighausen, Lothar

    2016-08-01

    Super-enhancers comprise dense transcription factor platforms highly enriched for active chromatin marks. A paucity of functional data led us to investigate the role of super-enhancers in the mammary gland, an organ characterized by exceptional gene regulatory dynamics during pregnancy. ChIP-seq analysis for the master regulator STAT5A, the glucocorticoid receptor, H3K27ac and MED1 identified 440 mammary-specific super-enhancers, half of which were associated with genes activated during pregnancy. We interrogated the Wap super-enhancer, generating mice carrying mutations in STAT5-binding sites within its constituent enhancers. Individually, the most distal site displayed the greatest enhancer activity. However, combinatorial mutation analysis showed that the 1,000-fold induction in gene expression during pregnancy relied on all enhancers. Disabling the binding sites of STAT5, NFIB and ELF5 in the proximal enhancer incapacitated the entire super-enhancer. Altogether, these data suggest a temporal and functional enhancer hierarchy. The identification of mammary-specific super-enhancers and the mechanistic exploration of the Wap locus provide insights into the regulation of cell-type-specific expression of hormone-sensing genes.

  5. Paracrine-acting adiponectin promotes mammary epithelial differentiation and synergizes with genistein to enhance transcriptional response to estrogen receptor beta signaling

    USDA-ARS?s Scientific Manuscript database

    Mammary stromal adipocytes constitute an active site for the synthesis of the adipokine adiponectin (APN) that may influence the mammary epithelial microenvironment. The relationship between 'local', mammary tissue-derived APN and breast cancer risk is poorly understood. Herein, we identify a novel ...

  6. Initiation of oncogenic transformation in human mammary epithelial cells by charged particles

    NASA Technical Reports Server (NTRS)

    Yang, T. C.; Georgy, K. A.; Craise, L. M.; Durante, M.

    1997-01-01

    Experimental studies have shown that high linear-energy transfer (LET) charged particles can be more effective than x-rays and gamma-rays in inducing oncogenic transformation in cultured cells and tumors in animals. Based on these results, experiments were designed and performed with an immortal human mammary epithelial cell line (H184B5), and several clones transformed by heavy ions were obtained. Cell fusion experiments were subsequently done, and results indicate that the transforming gene(s) is recessive. Chromosome analysis with fluorescence in situ hybridization (FISH) techniques also showed additional translocations in transformed human mammary epithelial cells. In addition, studies with these cell lines indicate that heavy ions can effectively induce deletion, break, and dicentrics. Deletion of tumor suppressor gene(s) and/or formation of translocation through DNA double strand breaks is a likely mechanism for the initiation of oncogenic transformation in human mammary epithelial cells.

  7. MicroRNAs in the development and neoplasia of the mammary gland.

    PubMed

    Jena, Manoj Kumar

    2017-01-01

    Study on the role of microRNAs (miRs) as regulators of gene expression through posttranscriptional gene silencing is currently gaining much interest,due to their wide involvement in different physiological processes. Understanding mammary gland development, lactation, and neoplasia in relation to miRs is essential. miR expression profiling of the mammary gland from different species in various developmental stages shows their role as critical regulators of development. miRs such as miR-126, miR-150, and miR-145 have been shown to be involved in lipid metabolism during lactation. In addition, lactogenic hormones influence miR expression as evidenced by overexpression of miR-148a in cow mammary epithelial cells, leading to enhanced lactation. Similarly, the miR-29 family modulates lactation-related gene expression by regulating DNA methylation of their promoters. Besides their role in development, lactation and involution, miRs are responsible for breast cancer development. Perturbed estrogen (E2) signaling is one of the major causes of breast cancer. Increased E2 levels cause altered expression of ERα, and ERα-miR cross-talk promotes tumour progression. miRs, such as miR-206, miR-34a, miR-17-5p, and miR-125 a/b are found to be tumour suppressors; whereas miR-21, miR-10B, and miR-155 are oncogenes. Oncogenic miRs like miR-21, miR-221, and miR-210 are overexpressed in triple negative breast cancer cases which can be diagnostic biomarker for this subtype of cancer.  This review focuses on the recent findings concerning the role of miRs in developmental stages of the mammary gland (mainly lactation and involution stages) and their involvement in breast cancer progression. Further studies in this area will help us to understand the molecular details of mammary gland biology, as well as miRs that could be therapeutic targets of breast cancer.

  8. Oxidative stress and inflammatory response biomarkers in dogs with mammary carcinoma.

    PubMed

    Machado, Vanessa S; Crivellenti, Leandro Z; Bottari, Nathieli B; Tonin, Alexandre A; Pelinson, Luana P; Borin-Crivellenti, Sofia; Santana, Aureo E; Torbitz, Vanessa D; Moresco, Rafael N; Duarte, Thiago; Duarte, Marta M M F; Schetinger, Maria Rosa C; Morsch, Vera M; Jaques, Jeandre A; Tinucci-Costa, Mirela; Da Silva, Aleksandro S

    2015-09-01

    Mammary carcinoma is the most common cancer that affects dogs, and in many cases it leads to death. Thus, given the importance of this disease, to clarify its pathogenesis is an important measure. In this sense, the aim of this study was to investigate the levels of cytokines and nitric oxide (NO), oxidative and antioxidant status, as well as the activity of adenosine deaminase (ADA) and butyrylcholinesterase (BChE) in dogs diagnosed with mammary carcinoma. With this purpose, thirty-three (33) serum samples from female dogs with histopathological diagnosis of mammary carcinoma, without evidence of metastasis, were used (group B). The material was classified based on the degree of malignancy, as follows: subgroup B1 (low-grade malignancy; n=26) and subgroup B2 (high grade of malignancy; n=7). Serum samples from healthy females (group A; n=10) were used as negative control. Our results showed that levels of cytokines (TNF-α, INF-γ, IL-1, and IL-6), NOx (nitrite/nitrate), AOPP (protein oxidation), and FRAP (antioxidant power) were significantly (P<0.05) increased in dogs with mammary carcinoma (group B), when compared with group A. On the other hand, ADA activity was significantly decreased (P<0.05) in both subgroups B1 and B2, when compared with group A. BChE activity, however, was reduced (P<0.05) only in subgroup B2 when compared with group A and subgroup B1. Unlike other variables, NO, AOPP, and IFN-γ were influenced by the degree of tumor malignancy, i.e., their levels were even higher in subgroup B2. Therefore, based on these results, we can conclude that all variables investigated are related to the pathogenesis of this disease, since they were altered in dogs with mammary tumor. Additionally, we suggest that ADA activity had an anti-inflammatory effect on these tumor samples, probably in order to modulate the inflammatory response. Copyright © 2015 Elsevier GmbH. All rights reserved.

  9. Flor-Essence? Herbal Tonic Promotes Mammary Tumor Development in Sprague Dawley Rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bennett, L; Montgomery, J; Steinberg, S

    Background: Women who are diagnosed with breast cancer often self-administer complementary and alternative medicines to augment their conventional treatments, improve health, or prevent recurrence. Flor-Essence{reg_sign} Tonic is a complex mixture of herbal extracts used by cancer patients because of anecdotal evidence that it can treat or prevent disease. Methods: Female Sprague Dawley rats were given water or exposed to 3% or 6% Flor-Essence{reg_sign} beginning at one day of age. Mammary tumors were induced with a single oral 40 mg/kg/bw dose of dimethylbenz(a)anthracene at 50 days of age and sacrificed at 23 weeks. Rats were maintained on AIN-76A diet. Results: Controlmore » rats had palpable mammary tumor incidence of 51.0% at 19 weeks of age compared to 65.0% and 59.4% for the 3% and 6% Flor-Essence{reg_sign} groups respectively. Overall, no significant difference in time until first palpable tumor was detected among any of the groups. At necropsy, mammary tumor incidence was 82.5% for controls compared to 90.0% and 97.3% for rats consuming 3% and 6% Flor-Essence{reg_sign}, respectively. Mean mammary tumor multiplicity ({+-}SES) for the controls was 2.8 ({+-} 0.5) and statistically different from the 3% or 6% Flor- Essence{reg_sign} groups with 5.2 ({+-} 0.7), and 4.8 ({+-} 0.6), respectively (p{<=}0.01). As expected, the majority of isolated tumors were diagnosed as adenocarcinomas. Conclusions: Flor-Essence{reg_sign} can promote mammary tumor development in the Sprague Dawley rat model. This observation is contrary to widely available anecdotal evidence as well as the desire of the consumer that this commercially available herbal tonic will suppress and/or inhibit tumor growth.« less

  10. Is intravenous urography required when ultrasonography and KUB evidence a ureteroscopy plan?

    PubMed

    Aghamir, Seyed Mohammad Kazem; Modaresi, Seyed Saeed; Salavati, Alborz; Aloosh, Mehdi; Meysami, Ali Pasha

    2012-01-01

    To determine whether pre-ureteroscopic stone extraction (USE) evaluation by intravenous urography (IVU) can change the clinical decision made on the basis of a plain X-ray of the kidneys, ureters, and bladder (KUB) plus an ultrasonography in the case of ureteral calculi. From October 2005 to November 2007, 139 USE candidates were selected based on ultrasonography and KUB, and were randomly divided into two groups. Each group was assessed by an expert urologist to decide about the treatment plans. Thereafter, all the patients underwent an IVU pre-operatively and were evaluated for the second time by the other urologist considering IVU. Presence of a hydronephrotic kidney on the ultrasonography, existence of a density in the probable tract of the ureter on KUB, and previous episodes of renal colic were considered as inclusion criteria. Exclusion criteria were non-opaque stones on KUB, hypersensitivity to contrast media, and serum creatinine > 1.5 mg/dL. On the basis of ultrasonography and KUB assessment, all of the patients were identified candidate for USE. According to secondary IVU-based planning, of 139 patients, 127 (91.3%) required USE, 10 (7.1%) ureteroscopy, and 2 (1.4%) non-operative treatment. About 8.7% of treatment plans was changed by IVU, which was not statistically significant (P = .35). Positive predictive value of ultrasonography plus KUB to diagnose a ureteral stone which needed USE was 92.8% while IVU is the gold standard (95% confidence interval: 92.38 to 93.22). Intravenous urography is not useful enough to be performed routinely before entire USEs.

  11. Use of ultrasonography to make management decisions

    USDA-ARS?s Scientific Manuscript database

    Transrectal ultrasonography has been available for making management decisions since the mid 1980’s. This technology allows for the real-time visualization of internal structures (i.e. ovary and fetus) that are otherwise difficult to evaluate. The use of this technology in making reproductive manag...

  12. Activation of int-1 and int-2 loci in GRf mammary tumors.

    PubMed

    Gray, D A; Jackson, D P; Percy, D H; Morris, V L

    1986-10-30

    The Mtv-2 locus is known to be associated with a high mammary tumor incidence (97%) and early development of mammary tumors (3-13 months) in GR mice. However, it was not previously known whether the provirus which resides at the Mtv-2 locus is tumorigenic in and of itself or whether reintegration of proviruses generated from Mtv-2 is required for tumorigenesis. Foster-nursing GR mice on C57/BL mice eliminates the milk-borne source of GR virus, and allows the study of Mtv-2 derived proviruses alone. Using this approach, we have tested predictions which follow from the "positional" versus "reintegrational" models of tumorigenesis. Specifically, we have examined tumors from primary foster-nursed (GRf) mice to determine if MMTV proviruses derived from Mtv-2 were scattered randomly throughout the genome or were clustered in the vicinity of the int-1 and int-2 loci, which are thought to be associated with mammary tumorigenesis. It was found that the majority of spontaneous GRf mammary tumors that were tested have MMTV proviral integrations in either or both of the int-1 and int-2 loci and have transcription of either or both of the int loci. Tumors induced by Mtv-2, therefore, appear to have arisen via a mechanism similar to the activation of the int loci by exogenous (milk-borne) MMTV proviruses.

  13. Carotid artery Doppler ultrasonography in retinal macroaneurysms.

    PubMed

    Thurairajan, G; Potamitis, T; Naylor, G; Gibson, J

    1998-01-01

    It is postulated that retinal arterial macroaneurysms (RAMs) occur at the site of incomplete embolic occlusion of a branch retinal artery. Embolic events of the retinal vessels are related to the state of the carotid artery tree and therefore Doppler ultrasonography of the carotid arteries in these patients is of particular interest. We have examined 13 patients with retinal artery macroaneurysms with carotid artery Doppler ultrasonography (CADU). Eight of these patients (61.5%) exhibited atheromatous plaques on the same side as the RAM with a moderate degree of arterial narrowing. Although our group of patients did not show advanced carotid artery disease, alterations of the arterial wall found at the level of the carotid artery were higher than expected in a similar hypertensive population. To our knowledge this is the first study of the carotid arterial tree in these patients. Our results support the theory that RAMs may be of embolic origin. Furthermore they demonstrate that CADU is a useful investigation in patients with RAMs.

  14. Multidisciplinary Biomarkers of Early Mammary Carcinogenesis

    DTIC Science & Technology

    2009-04-01

    ABSTRACT The purpose of the proposed research is to develop novel optical technologies to identify high-risk premalignant changes in the breast ...Our proposed research will first test specific optical parameters in breast cancer cell lines and models of early mammary carcinogenesis, and then...develop methods to test the optical parameters in random periareolar fine needle aspirate (RPFNA) samples from women at high-risk for developing breast

  15. Creation and Validation of a Simulator for Neonatal Brain Ultrasonography: A Pilot Study.

    PubMed

    Tsai, Andy; Barnewolt, Carol E; Prahbu, Sanjay P; Yonekura, Reimi; Hosmer, Andrew; Schulz, Noah E; Weinstock, Peter H

    2017-01-01

    Historically, skills training in performing brain ultrasonography has been limited to hours of scanning infants for lack of adequate synthetic models or alternatives. The aim of this study was to create a simulator and determine its utility as an educational tool in teaching the skills that can be used in performing brain ultrasonography on infants. A brain ultrasonography simulator was created using a combination of multi-modality imaging, three-dimensional printing, material and acoustic engineering, and sculpting and molding. Radiology residents participated prior to their pediatric rotation. The study included (1) an initial questionnaire and resident creation of three coronal images using the simulator; (2) brain ultrasonography lecture; (3) hands-on simulator practice; and (4) a follow-up questionnaire and re-creation of the same three coronal images on the simulator. A blinded radiologist scored the quality of the pre- and post-training images using metrics including symmetry of the images and inclusion of predetermined landmarks. Wilcoxon rank-sum test was used to compare pre- and post-training questionnaire rankings and image quality scores. Ten residents participated in the study. Analysis of pre- and post-training rankings showed improvements in technical knowledge and confidence, and reduction in anxiety in performing brain ultrasonography. Objective measures of image quality likewise improved. Mean reported value score for simulator training was high across participants who reported perceived improvements in scanning skills and enjoyment from simulator use, with interest in additional practice on the simulator and recommendations for its use. This pilot study supports the use of a simulator in teaching radiology residents the skills that can be used to perform brain ultrasonography. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  16. Functional adaptations of the transcriptome to mastitis-causing pathogens: the mammary gland and beyond.

    PubMed

    Loor, Juan J; Moyes, Kasey M; Bionaz, Massimo

    2011-12-01

    Application of microarrays to the study of intramammary infections in recent years has provided a wealth of fundamental information on the transcriptomics adaptation of tissue/cells to the disease. Due to its heavy toll on productivity and health of the animal, in vivo and in vitro transcriptomics works involving different mastitis-causing pathogens have been conducted on the mammary gland, primarily on livestock species such as cow and sheep, with few studies in non-ruminants. However, the response to an infectious challenge originating in the mammary gland elicits systemic responses in the animal and encompasses tissues such as liver and immune cells in the circulation, with also potential effects on other tissues such as adipose. The susceptibility of the animal to develop mastitis likely is affected by factors beyond the mammary gland, e.g. negative energy balance as it occurs around parturition. Objectives of this review are to discuss the use of systems biology concepts for the holistic study of animal responses to intramammary infection; providing an update of recent work using transcriptomics to study mammary and peripheral tissue (i.e. liver) as well as neutrophils and macrophage responses to mastitis-causing pathogens; discuss the effect of negative energy balance on mastitis predisposition; and analyze the bovine and murine mammary innate-immune responses during lactation and involution using a novel functional analysis approach to uncover potential predisposing factors to mastitis throughout an animal's productive life.

  17. Histopathological and in vivo evidence of regucalcin as a protective molecule in mammary gland carcinogenesis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Marques, Ricardo; Vaz, Cátia V.; Maia, Cláudio J.

    Regucalcin (RGN) is a calcium-binding protein, which has been shown to be underexpressed in cancer cases. This study aimed to determine the association of RGN expression with clinicopathological parameters of human breast cancer. In addition, the role of RGN in malignancy of mammary gland using transgenic rats overexpressing the protein (Tg-RGN) was investigated. Wild-type (Wt) and Tg-RGN rats were treated with 7,12-dimethylbenz[α]anthracene (DMBA). Carcinogen-induced tumors were histologically classified and the Ki67 proliferation index was estimated. Immunohistochemistry analysis showed that RGN immunoreactivity was negatively correlated with the histological grade of breast infiltrating ductal carcinoma suggesting that progression of breast cancer ismore » associated with loss of RGN. Tg-RGN rats displayed lower incidence of carcinogen-induced mammary gland tumors, as well as lower incidence of invasive forms. Moreover, higher proliferation was observed in non-invasive tumors of Wt animals comparatively with Tg-RGN. Overexpression of RGN was associated with diminished expression of cell-cycle inhibitors and increased expression of apoptosis inducers. Augmented activity of apoptosis effector caspase-3 was found in the mammary gland of Tg-RGN. RGN overexpression protected from carcinogen-induced mammary gland tumor development and was linked with reduced proliferation and increased apoptosis. These findings indicated the protective role of RGN in the carcinogenesis of mammary gland. - Highlights: • RGN immunoreactivity was negatively correlated with breast cancer differentiation. • Transgenic overexpression of RGN diminished incidence of carcinogen-induced tumors. • Transgenic overexpression of RGN restricted proliferation and fostered apoptosis. • RGN has a protective role in the carcinogenesis of mammary gland.« less

  18. Precursors of hexoneogenesis within the human mammary gland

    USDA-ARS?s Scientific Manuscript database

    The human mammary gland is capable of de novo synthesis of glucose and galactose (hexoneogenesis); however, the carbon source is incompletely understood. In this study, we investigated the role of acetate, glutamine, lactate and glycerol as potential carbon sources for hexoneogenesis. Healthy breast...

  19. [Color Doppler ultrasonography--a new imaging procedure in maxillofacial surgery].

    PubMed

    Reinert, S; Lentrodt, J

    1991-01-01

    Colour Doppler ultrasonography shows blood flow in real time and colour by combining the features of real time B mode ultrasound and Doppler. At each point in the image the returning signal is interrogated for both amplitude and frequency information. The resulting image shows all non-moving structures in shades of gray and moving structures in shades of red or blue depending on direction and velocity. The technique of colour Doppler ultrasonography and our experiences in 63 examinations are described. The clinical application of this new simple non-invasive method in maxillo-facial surgery is discussed.

  20. SDF-1 in Mammary Fibroblasts of Bovine with Mastitis Induces EMT and Inflammatory Response of Epithelial Cells.

    PubMed

    He, Guiliang; Ma, Mengru; Yang, Wei; Wang, Hao; Zhang, Yong; Gao, Ming-Qing

    2017-01-01

    Fibroblasts constitute the majority of the stromal cells within bovine mammary gland, yet the functional contributions of these cells to mastitis and fibrosis and the mechanism are poorly understood. In this study, we demonstrate that inflammation-associated fibroblasts (INFs) extracted from bovine mammary glands with clinical mastitis had different expression pattern regarding to several extracellular matrix (ECM) proteins, chemokines and cytokines compared to normal fibroblasts (NFs) from dairy cows during lactation. The INFs induced epithelial-mesenchymal transition (EMT) and inflammatory responses of mammary epithelial cells in a vitro co-culture model. These functional contributions of INFs to normal epithelial cells were mediated through their ability to secrete stromal cell-derived factor 1 (SDF-1). SDF-1 was highly secreted/expressed by INFs, lipopolysaccharide (LPS) -treated NFs, lipoteichoic acid (LTA) -treated NFs, as well as mastitic tissue compared to their counterparts. Exogenous SDF-1 promoted EMT on epithelial cells through activating NF-κB pathway, induced inflammation response and inhibited proliferation of epithelial cells. In addition, SDF-1 was able to induce mastitis and slight fibrosis of mouse mammary gland, which was attenuated by a specific inhibitor of the receptor of SDF-1. Our findings indicate that stromal fibroblasts within mammary glands with mastitis contribute to EMT and inflammatory responses of epithelial cells through the secretion of SDF-1, which could result in the inflammation spread and fibrosis within mammary gland.

  1. Mixed tocopherols prevent mammary tumorigenesis by inhibiting estrogen action and activating PPAR-γ

    PubMed Central

    Lee, Hong Jin; Ju, Jihyeung; Paul, Shiby; So, Jae-Young; DeCastro, Andrew; Smolarek, Amanda; Lee, Mao-Jung; Yang, Chung S.; Newmark, Harold L.; Suh, Nanjoo

    2009-01-01

    Purpose Tocopherols are lipophilic antioxidants present in vegetable oils. Although the antioxidant and anticancer activities of α-tocopherol (vitamin E) have been studied for decades, recent intervention studies with α-tocopherol have been negative for protection from cancer in humans. The tocopherols consist of 4 isoforms, α, β, γ, and δ variants, and recent attention is being made to other isoforms. In the present study, we investigated the inhibitory effect of a tocopherol mixture rich in γ- and δ-tocopherols against mammary tumorigenesis. Experimental Design Female Sprague Dawley rats were treated with N-methyl-N-nitrosourea (NMU), and then fed diets containing 0.1%, 0.3%, or 0.5% mixed tocopherols rich in γ- and δ-tocopherols for 9 weeks. Tumor burden and multiplicity were determined, and the levels of markers of inflammation, proliferation and apoptosis were evaluated in the serum and in mammary tumors. The regulation of nuclear receptor signaling by tocopherols was studied in mammary tumors and in breast cancer cells. Results Dietary administration of 0.1%, 0.3%, or 0.5% mixed tocopherols suppressed mammary tumor growth by 38%, 50%, or 80%, respectively. Tumor multiplicity was also significantly reduced in all three mixed tocopherol groups. Mixed tocopherols increased the expression of p21, p27, caspase-3 and peroxisome proliferator activated receptor-γ (PPAR-γ), and inhibited AKT and estrogen signaling in mammary tumors. Our mechanistic study found that γ- and δ-tocopherols, but not α-tocopherol, activated PPAR-γ and antagonized estrogen action in breast cancer. Conclusion The results suggest that γ- and δ-tocopherols may be effective agents for the prevention of breast cancer. PMID:19509159

  2. Evolution of immune functions of the mammary gland and protection of the infant.

    PubMed

    Goldman, Armond S

    2012-06-01

    Abstract The evolution of immunological agents in milk is intertwined with the general aspects of the evolution of the mammary gland. In that respect, mammalian precursors emerged from basal amniotes some 300 million years ago. In contrast to the predominant dinosaurs, proto-mammals possessed a glandular skin. A secondary palate in the roof of the mouth that directed airflow from the nostrils to the oropharynx and thus allowed mammals to ingest and breathe simultaneously first appeared in cynodonts 230 million years ago. This set the stage for mammalian newborns to nurse from the future mammary gland. Interplays between environmental and genetic changes shaped mammalian evolution including the mammary gland from dermal glands some 160 millions of years ago. It is likely that secretions from early mammary glands provided nutrients and immunological agents for the infant. Natural selection culminated in milks uniquely suited to nourish and protect infants of each species. In human milk, antimicrobial, anti-inflammatory, and immunoregulatory agents and living leukocytes are qualitatively or quantitatively different from those in other mammalian milks. Those in human milk compensate for developmental delays in the immunological system of the recipient infant. Consequently, the immune system in human milk provided by evolution is much of the basis for encouraging breastfeeding for human infants.

  3. Canonical Wnt Signaling as a Specific Mark of Normal and Tumorigenic Mammary Stem Cells

    DTIC Science & Technology

    2011-02-01

    aggressive mammary tumors. 15. SUBJECT TERMS Breast cancer stem cells, Wnt signaling, canonical Wnt signaling, B-catenin, normal stem cells, adult stem...Wnt pathway is associated with abnormal mouse mammary development, tumorigenesis, and human breast cancer. In addition, increasing evidence suggests...activation occurs in human breast cancer and is required for proliferation of various other stem cell compartments, addressing how Wnt signaling promotes

  4. Primary mammary mucinous cystadenocarcinoma: cytological and histological findings.

    PubMed

    Sentani, Kazuhiro; Tashiro, Takashi; Uraoka, Naohiro; Aosaki, Yoriyuki; Yano, Satomi; Takaeko, Fumio; Yasui, Wataru

    2012-07-01

    Mucinous cystadenocarcinoma (MCA), commonly encountered in the ovary or pancreas, is rare in the breast and was only recently described as a distinct variant of invasive ductal carcinoma of the breast. Only 11 cases of primary mammary MCA have been reported. In this article, we report a case of primary mammary MCA with focus on cytological and histological findings. A 65-year-old female noticed right palpable breast mass. Sonography showed an irregularly shaped 2.8 × 2.4 cm lesion in the upper outer quadrant of the right breast. Fine-needle aspiration cytology was performed on the right breast nodule, and cytopathologic examination suggested an adenocarcinoma composed of tall columnar cells with mucin. A partial mastectomy of the right breast and the axillary lymph nodes dissection was performed. The gross examination revealed a well-demarcated and mucus-filled tumor. Histologically, it had complex papillae, some of which were supported by delicate fibrovascular stroma lined by simple to slightly stratified columnar neoplastic epithelial cells with intracellular mucin, coexisting with MCA in situ and ordinary intraductal carcinoma component (ICC). Immunohistochemically, ICC was HER2-negative and estrogen receptor/progesterone receptor-positive, while MCA was triple negative. MCA might be derived from a metaplasia of ordinary ICC, but its pathogenesis and biologic behavior remains unclear. Despite the invasive nature of mammary MCA, these carcinomas appear to be associated with a good prognosis. The patient has remained well and disease-free for 6 months after the operation. Copyright © 2011 Wiley Periodicals, Inc.

  5. Mammary gland-specific nuclear factor activity is positively regulated by lactogenic hormones and negatively by milk stasis.

    PubMed

    Schmitt-Ney, M; Happ, B; Hofer, P; Hynes, N E; Groner, B

    1992-12-01

    The mammary gland-specific nuclear factor (MGF) is a crucial contributor to the regulation of transcription from the beta-casein gene promoter. The beta-casein gene encodes a major milk protein, which is expressed in mammary epithelial cells during lactation and can be induced by lactogenic hormones in the clonal mammary epithelial cell line HC11. We have investigated the specific DNA-binding activity of MGF in mammary epithelial cells in vivo and in vitro. Comparison of MGF in HC11 cells and mammary gland cells from lactating mice revealed molecules with identical DNA-binding properties. Bandshift and UV cross-linking experiments indicated that MGF in HC11 cells has a higher mol wt than MGF found in mice. Little MGF activity was detected in nuclear extracts from HC11 cells cultured in the absence of lactogenic hormones. Lactogenic hormone treatment of HC11 cells led to a strong induction of MGF activity. The induction of MGF activity as well as utilization of the beta-casein promoter were suppressed when epidermal growth factor was present in the tissue culture medium simultaneously with the lactogenic hormones. In lactating animals, MGF activity is regulated by suckling, milk stasis, and systemic hormone signals. The mammary glands from maximally lactating animals, 16 days postpartum, contain drastically reduced MGF activity after removal of the pups for only 8 h. The down-regulation of MGF by pup withdrawal was slower in early lactation, 6 days postpartum. We also investigated the relative contributions of local signals, generated by milk stasis, and systemic hormone signals to the regulation of MGF activity. The access to one row of mammary glands of lactating mothers was denied to the pups for 24 h. High levels of MGF were found in the accessible mammary glands, and intermediate levels of MGF were found in the inaccessible glands of the same mouse. Very low MGF levels were detected when the pups were removed from the dams for 24 h. We conclude that systemic as

  6. Accuracy of ultrasonography and magnetic resonance imaging in the diagnosis of placenta accreta.

    PubMed

    Riteau, Anne-Sophie; Tassin, Mikael; Chambon, Guillemette; Le Vaillant, Claudine; de Laveaucoupet, Jocelyne; Quéré, Marie-Pierre; Joubert, Madeleine; Prevot, Sophie; Philippe, Henri-Jean; Benachi, Alexandra

    2014-01-01

    To evaluate the accuracy of ultrasonography and magnetic resonance imaging (MRI) in the diagnosis of placenta accreta and to define the most relevant specific ultrasound and MRI features that may predict placental invasion. This study was approved by the institutional review board of the French College of Obstetricians and Gynecologists. We retrospectively reviewed the medical records of all patients referred for suspected placenta accreta to two university hospitals from 01/2001 to 05/2012. Our study population included 42 pregnant women who had been investigated by both ultrasonography and MRI. Ultrasound images and MRI were blindly reassessed for each case by 2 raters in order to score features that predict abnormal placental invasion. Sensitivity in the diagnosis of placenta accreta was 100% with ultrasound and 76.9% for MRI (P = 0.03). Specificity was 37.5% with ultrasonography and 50% for MRI (P = 0.6). The features of greatest sensitivity on ultrasonography were intraplacental lacunae and loss of the normal retroplacental clear space. Increased vascularization in the uterine serosa-bladder wall interface and vascularization perpendicular to the uterine wall had the best positive predictive value (92%). At MRI, uterine bulging had the best positive predictive value (85%) and its combination with the presence of dark intraplacental bands on T2-weighted images improved the predictive value to 90%. Ultrasound imaging is the mainstay of screening for placenta accreta. MRI appears to be complementary to ultrasonography, especially when there are few ultrasound signs.

  7. Bioengineered silk scaffolds in 3D tissue modeling with focus on mammary tissues.

    PubMed

    Maghdouri-White, Yas; Bowlin, Gary L; Lemmon, Christopher A; Dréau, Didier

    2016-02-01

    In vitro generation of three-dimensional (3D) biological tissues and organ-like structures is a promising strategy to study and closely model complex aspects of the molecular, cellular, and physiological interactions of tissue. In particular, in vitro 3D tissue modeling holds promises to further our understanding of breast development. Indeed, biologically relevant 3D structures that combine mammary cells and engineered matrices have improved our knowledge of mammary tissue growth, organization, and differentiation. Several polymeric biomaterials have been used as scaffolds to engineer 3D mammary tissues. Among those, silk fibroin-based biomaterials have many biologically relevant properties and have been successfully used in multiple medical applications. Here, we review the recent advances in engineered scaffolds with an emphasis on breast-like tissue generation and the benefits of modified silk-based scaffolds. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Comparison of the transcriptpmes of long-tern label retaining-cells and C cells microdissected from mammary epithelium: an initial study to character potential stem/progenitor cells

    USDA-ARS?s Scientific Manuscript database

    Mammary stem cells (MaSC) account for the cell lineage of mammary epithelia and provide for mammary growth, development and tissue homeostasis. The presence of MaSC was clearly demonstrated by the generation of an entire mammary gland from a single cell implanted into epithelium-ablated mammary fat...

  9. Presence of hyperplastic pectoral mammary glands in a white-footed mouse (Peromyscus leucopus) from a Superfund Site in Oklahoma, USA.

    PubMed

    Hays, Kimberly A; Breshears, Melanie A

    2011-01-01

    Laboratory experiments have documented the effects of hormones and endocrine-disrupting compounds on mammary development in mammals. However, few observations of mammary hyperplasia have been presented for wild rodents. We describe hyperplastic mammary glands in a wild-caught white-footed mouse (Peromyscus leucopus) from an area contaminated with heavy metals.

  10. Diagnostic accuracy of oblique chest radiograph for occult pneumothorax: comparison with ultrasonography.

    PubMed

    Matsumoto, Shokei; Sekine, Kazuhiko; Funabiki, Tomohiro; Orita, Tomohiko; Shimizu, Masayuki; Hayashida, Kei; Kazamaki, Taku; Suzuki, Tatsuya; Kishikawa, Masanobu; Yamazaki, Motoyasu; Kitano, Mitsuhide

    2016-01-01

    An occult pneumothorax is a pneumothorax that is not seen on a supine chest X-ray but is detected by computed tomography scanning. However, critical patients are difficult to transport to the computed tomography suite. We previously reported a method to detect occult pneumothorax using oblique chest radiography (OXR). Several authors have also reported that ultrasonography is an effective technique for detecting occult pneumothorax. The aim of this study was to evaluate the usefulness of OXR in the diagnosis of the occult pneumothorax and to compare OXR with ultrasonography. All consecutive blunt chest trauma patients with clinically suspected pneumothorax on arrival at the emergency department were prospectively included at our tertiary-care center. The patients underwent OXR and ultrasonography, and underwent computed tomography scans as the gold standard. Occult pneumothorax size on computed tomography was classified as minuscule, anterior, or anterolateral. One hundred and fifty-nine patients were enrolled. Of the 70 occult pneumothoraces found in the 318 thoraces, 19 were minuscule, 32 were anterior, and 19 were anterolateral. The sensitivity and specificity of OXR for detecting occult pneumothorax was 61.4 % and 99.2 %, respectively. The sensitivity and specificity of lung ultrasonography was 62.9 % and 98.8 %, respectively. Among 27 occult pneumothoraces that could not be detected by OXR, 16 were minuscule and 21 could be conservatively managed without thoracostomy. OXR appears to be as good method as lung ultrasonography in the detection of large occult pneumothorax. In trauma patients who are difficult to transfer to computed tomography scan, OXR may be effective at detecting occult pneumothorax with a risk of progression.

  11. Ultrasonography in gastroenterology.

    PubMed

    Ødegaard, Svein; Nesje, Lars B; Hausken, Trygve; Gilja, Odd Helge

    2015-06-01

    Ultrasonography (US) is a safe and available real-time, high-resolution imaging method, which during the last decades has been increasingly integrated as a clinical tool in gastroenterology. New US applications have emerged with enforced data software and new technical solutions, including strain evaluation, three-dimensional imaging and use of ultrasound contrast agents. Specific gastroenterologic applications have been developed by combining US with other diagnostic or therapeutic methods, such as endoscopy, manometry, puncture needles, diathermy and stents. US provides detailed structural information about visceral organs without hazard to the patients and can play an important clinical role by reducing the need for invasive procedures. This paper presents different aspects of US in gastroenterology, with a special emphasis on the contribution from Nordic scientists in developing clinical applications.

  12. Diagnostic ultrasonography in cattle with abdominal fat necrosis.

    PubMed

    Tharwat, Mohamed; Buczinski, Sébastien

    2012-01-01

    This study describes the ultrasonographic findings in 14 cows with abdominal fat necrosis. Ultrasonography of the abdomen revealed the presence of heterogeneous hyperechoic masses and hyperechoic omentum with localized masses floating in a hypoechoic peritoneal fluid. A hyperechogenic rim was imaged around both kidneys. The intestines were coated with hyperechoic capsules and the intestinal lumens were constricted. Ultrasonographic examination of the pancreatic parenchyma showed an overall increased echogenicity which was homogenously distributed in 3 cases. A diagnosis of abdominal fat necrosis was made with ultrasound-guided biopsy of the echogenic masses, and thereafter at postmortem examination. Results from this study demonstrate the efficacy of ultrasonography as an imaging modality for antemortem diagnosis of abdominal lipomatosis in cattle. To the authors' knowledge, this study is the first that illustrates ultrasonographic findings in cattle affected with abdominal lipomatosis.

  13. Diagnosis of Nipple Discharge: Value of Magnetic Resonance Imaging and Ultrasonography in Comparison with Ductoscopy.

    PubMed

    Yılmaz, Ravza; Bender, Ömer; Çelik Yabul, Fatma; Dursun, Menduh; Tunacı, Mehtap; Acunas, Gülden

    2017-04-05

    Pathologic nipple discharge, which is a common reason for referral to the breast imaging service, refers to spontaneous or bloody nipple discharge that arises from a single duct. The most common cause of nipple discharge is benign breast lesions, such as solitary intraductal papilloma and papillomatosis. Nevertheless, in rare cases, a malignant cause of nipple discharge can be found. To study the diagnostic value of ultrasonography, magnetic resonance imaging, and ductoscopy in patients with pathologic nipple discharge, compare their efficacy, and investigate the importance of magnetic resonance imaging in the diagnosis of intraductal pathologies. Diagnostic accuracy study. Fifty patients with pathologic nipple discharge were evaluated by ultrasonography and magnetic resonance imaging. Of these, 44 ductoscopic investigations were made. The patients were classified according to magnetic resonance imaging, ultrasonography, and ductoscopy findings. A total of 25 patients, whose findings were reported as intraductal masses, underwent surgery oincluding endoscopic excision for two endoscopic excision. Findings were compared with the pathology results that were accepted as the gold standard in the description of the aetiology of nipple discharge. In addition, magnetic resonance imaging, ultrasonography and ductoscopy findings were analysed comparatively in patients who had no surgery. Intraductal masses were reported in 26 patients, 20 of whom operated and established accurate diagnosis of 18 patients on magnetic resonance imaging. According to the ultrasonography, intraductal masses were identified in 22 patients, 17 of whom underwent surgery. Ultrasonography established accurate diagnoses in 15 patients. Intraductal mass was identified in 22 patients and ductoscopy established accurate diagnoses based on histopathologic results in 16 patients. The sensitivities of methods were 75% in ultrasonography, 90% in magnetic resonance imaging, and 94.6% in ductoscopy. The

  14. Comparative proteomic analysis of proteins expression changes in the mammary tissue of cows infected with Escherichia coli mastitis.

    PubMed

    Zhao, Xiao-wei; Yang, Yong-xin; Huang, Dong-wei; Cheng, Guang-long; Zhao, Hui-ling

    2015-01-01

    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 a-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.

  15. Comparative proteomic analysis of proteins expression changes in the mammary tissue of cows infected with Escherichia coli mastitis

    PubMed Central

    Zhao, Xiao-wei; Huang, Dong-wei; Cheng, Guang-long; Zhao, Hui-ling

    2015-01-01

    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 α-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. PMID:25549220

  16. Carcinoma of the pancreatic head and periampullary region. Tumor staging with laparoscopy and laparoscopic ultrasonography.

    PubMed Central

    John, T G; Greig, J D; Carter, D C; Garden, O J

    1995-01-01

    OBJECTIVE: The authors performed a prospective evaluation of staging laparoscopy with laparoscopic ultrasonography in predicting surgical resectability in patients with carcinomas of the pancreatic head and periampullary region. SUMMARY BACKGROUND DATA: Pancreatic resection with curative intent is possible in a select minority of patients who have carcinomas of the pancreatic head and periampullary region. Patient selection is important to plan appropriate therapy and avoid unnecessary laparotomy in patients with unresectable disease. Laparoscopic ultrasonography is a novel technique that combines the proven benefits of staging laparoscopy with high resolution intraoperative ultrasound of the liver and pancreas, but which has yet to be evaluated critically in the staging of pancreatic malignancy. METHODS: A cohort of 40 consecutive patients referred to a tertiary referral center and with a diagnosis of potentially resectable pancreatic or periampullary cancer underwent staging laparoscopy with laparoscopic ultrasonography. The diagnostic accuracy of staging laparoscopy alone and in conjunction with laparoscopic ultrasonography was evaluated in predicting tumor resectability (absence of peritoneal or liver metastases; absence of malignant regional lymphadenopathy; tumor confined to pancreatic head or periampullary region). RESULTS: "Occult" metastatic lesions were demonstrated by staging laparoscopy in 14 patients (35%). Laparoscopic ultrasonography demonstrated factors confirming unresectable tumor in 23 patients (59%), provided staging information in addition to that of laparoscopy alone in 20 patients (53%), and changed the decision regarding tumor resectability in 10 patients (25%). Staging laparoscopy with laparoscopic ultrasonography was more specific and accurate in predicting tumor resectability than laparoscopy alone (88% and 89% versus 50% and 65%, respectively). CONCLUSIONS: Staging laparoscopy is indispensable in the detection of "occult" intra

  17. Prenatal diagnosis of placenta accreta by colour Doppler ultrasonography: 5-year review.

    PubMed

    Pongrojpaw, Densak; Chanthasenanont, Athita; Nanthakomon, Tongta; Suwannarurk, Komsun

    2014-08-01

    To determine the accuracy of colour Doppler ultrasonography to diagnose placenta accreta. The authors reviewed cases of placenta accreta between January, 2008 and December, 2012. Ultrasonographic images consistent with signs ofplacenta accreta (numerous vascular lacunae, loss ofsubplacentalsonolucent space, absent lower uterine segment between bladder-placenta, turbulent or complicated blood flow at the uteroplacental interface) were correlated with findings at the time of surgery and pathologic examination. Over 60 months, 12 cases (0.48/1,000 deliveries) with suspected placenta accreta by ultrasonography were studied. The median gestational age atfirst diagnosis was 24 weeks. All cases had at least one previous cesarean delivery. At surgery, all cases had an adherent placenta requiring hysterectomy (five accreta, three increta, andfourpercreta). Four cases (33%) had accidental tear of urinary bladder Nine cases (75%) required blood transfusions. Colour Doppler ultrasonography appears useful in antenatal diagnosis ofplacenta accreta.

  18. Amplification of tumor inducing putative cancer stem cells (CSCs) by vitamin A/retinol from mammary tumors

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sharma, Rohit B.; Wang, Qingde; Khillan, Jaspal S., E-mail: khillan@pitt.edu

    Highlights: •Vitamin A supports self renewal of putative CSCs from mammary tumors. •These cells exhibit impaired retinol metabolism into retinoic acid. •CSCs from mammary tumors differentiate into mammary specific cell lineages. •The cells express mammary stem cell specific CD29 and CD49f markers. •Putative CSCs form highly metastatic tumors in NOD SCID mouse. -- Abstract: Solid tumors contain a rare population of cancer stem cells (CSCs) that are responsible for relapse and metastasis. The existence of CSC however, remains highly controversial issue. Here we present the evidence for putative CSCs from mammary tumors amplified by vitamin A/retinol signaling. The cells exhibitmore » mammary stem cell specific CD29{sup hi}/CD49f{sup hi}/CD24{sup hi} markers, resistance to radiation and chemo therapeutic agents and form highly metastatic tumors in NOD/SCID mice. The cells exhibit indefinite self renewal as cell lines. Furthermore, the cells exhibit impaired retinol metabolism and do not express enzymes that metabolize retinol into retinoic acid. Vitamin A/retinol also amplified putative CSCs from breast cancer cell lines that form highly aggressive tumors in NOD SCID mice. The studies suggest that high purity putative CSCs can be isolated from solid tumors to establish patient specific cell lines for personalized therapeutics for pre-clinical translational applications. Characterization of CSCs will allow understanding of basic cellular and molecular pathways that are deregulated, mechanisms of tumor metastasis and evasion of therapies that has direct clinical relevance.« less

  19. Pharmacodynamics and Medicinal Chemistry of an External Chinese Herbal Formula for Mammary Precancerous Lesions

    PubMed Central

    Zhang, Guijuan; Ma, Yi; Fan, Hongxia

    2017-01-01

    Ruyan Neixiao Cream (RYNXC) is a traditional Chinese herbal formula for treating mammary precancerous disease. This study was carried out to investigate in vivo anticancer effect of RYNXC and multiple constituents. 32 virginal Sprague-Dawley rats were randomly divided into blank control group (BC), mammary precancer models group (MODEL), tamoxifen group (TAM), and Ruyan Neixiao Cream group (RYNXC). TAM was intervened by tamoxifen; RYNXC was intervened by Ruyan Neixiao Cream. The chromatographic separation was performed by high performance liquid chromatography (HPLC) coupled with mass spectrometry (MS). RYNXC showed significant improvement in erythrocyte aggregation index (EAI), hematocrit (HCT), fibrinogen (FIB), spleen coefficient, and uterus coefficient compared with MODEL. In RYNXC and TAM groups, atypical hyperplasia was observed in pathological mammary tissues; meanwhile in MODEL group, ductal carcinoma was observed in situ. Moreover, fifteen compounds were characterized according to HPLC-MS data, including organic acids, tannin, alkaloid, volatile oil, anthraquinones, and flavonoids. The study suggests that RYNXC was an effective Chinese herbal formula for mammary precancerous lesions and provides a scientific basis for the quality standard and the pharmacology of RYNXC. It will be beneficial to the future clinical application of RYNXC. PMID:28811827

  20. Effects of xanthosine in isoform switch and splice variants of expressed genes in mammary epithelial cells

    USDA-ARS?s Scientific Manuscript database

    Although intramammary xanthosine (XS) treatment was reported to increase the mammary stem cell population and milk yield in bovine and caprine, underlying molecular mechanisms remain unclear. The goal of this study was to evaluate effects of XS treatment on the mammary transcriptome in early-lactati...

  1. Apical electrolyte concentration modulates barrier function and tight junction protein localization in bovine mammary epithelium.

    PubMed

    Quesnell, Rebecca R; Erickson, Jamie; Schultz, Bruce D

    2007-01-01

    In vitro mammary epithelial cell models typically fail to form a consistently tight barrier that can effectively separate blood from milk. Our hypothesis was that mammary epithelial barrier function would be affected by changes in luminal ion concentration and inflammatory cytokines. Bovine mammary epithelial (BME-UV cell line) cells were grown to confluence on permeable supports with a standard basolateral medium and either high-electrolyte (H-elec) or low-electrolyte (L-elec) apical medium for 14 days. Apical media were changed to/from H-elec medium at predetermined times prior to assay. Transepithelial electrical resistance (R(te)) was highest in monolayers continuously exposed to apical L-elec. A time-dependent decline in R(te) began within 24 h of H-elec medium exposure. Change from H-elec medium to L-elec medium time-dependently increased R(te). Permeation by FITC-conjugated dextran was elevated across monolayers exposed to H-elec, suggesting compromise of a paracellular pathway. Significant alteration in occludin distribution was evident, concomitant with the changes in R(te), although total occludin was unchanged. Neither substitution of Na(+) with N-methyl-d-glucosamine (NMDG(+)) nor pharmacological inhibition of transcellular Na(+) transport pathways abrogated the effects of apical H-elec medium on R(te). Tumor necrosis factor alpha, but not interleukin-1beta nor interleukin-6, in the apical compartment caused a significant decrease in R(te) within 8 h. These results indicate that mammary epithelium is a dynamic barrier whose cell-cell contacts are acutely modulated by cytokines and luminal electrolyte environment. Results not only demonstrate that BME-UV cells are a model system representative of mammary epithelium but also provide critical information that can be applied to other mammary model systems to improve their physiological relevance.

  2. Epigenetic Modifications Unlock the Milk Protein Gene Loci during Mouse Mammary Gland Development and Differentiation

    PubMed Central

    Rijnkels, Monique; Freeman-Zadrowski, Courtneay; Hernandez, Joseph; Potluri, Vani; Wang, Liguo; Li, Wei; Lemay, Danielle G.

    2013-01-01

    Background Unlike other tissues, development and differentiation of the mammary gland occur mostly after birth. The roles of systemic hormones and local growth factors important for this development and functional differentiation are well-studied. In other tissues, it has been shown that chromatin organization plays a key role in transcriptional regulation and underlies epigenetic regulation during development and differentiation. However, the role of chromatin organization in mammary gland development and differentiation is less well-defined. Here, we have studied the changes in chromatin organization at the milk protein gene loci (casein, whey acidic protein, and others) in the mouse mammary gland before and after functional differentiation. Methodology/Principal Findings Distal regulatory elements within the casein gene cluster and whey acidic protein gene region have an open chromatin organization after pubertal development, while proximal promoters only gain open-chromatin marks during pregnancy in conjunction with the major induction of their expression. In contrast, other milk protein genes, such as alpha-lactalbumin, already have an open chromatin organization in the mature virgin gland. Changes in chromatin organization in the casein gene cluster region that are present after puberty persisted after lactation has ceased, while the changes which occurred during pregnancy at the gene promoters were not maintained. In general, mammary gland expressed genes and their regulatory elements exhibit developmental stage- and tissue-specific chromatin organization. Conclusions/Significance A progressive gain of epigenetic marks indicative of open/active chromatin on genes marking functional differentiation accompanies the development of the mammary gland. These results support a model in which a chromatin organization is established during pubertal development that is then poised to respond to the systemic hormonal signals of pregnancy and lactation to achieve the

  3. Chemoprevention and therapy of mouse mammary carcinomas with doxorubicin encapsulated in sterically stabilized liposomes.

    PubMed

    Vaage, J; Donovan, D; Loftus, T; Abra, R; Working, P; Huang, A

    1994-05-01

    The objective of this study was to determine the ability of doxorubicin, encapsulated in sterically stabilized liposomes (Doxil [Liposome Technology, Inc., Menlo Park, CA]), to inhibit the spontaneous development of mammary carcinomas in mice. Monthly prophylactic intravenous injections of 6 mg/kg doses of Doxil were started when retired breeding C3H/He mice were 26 weeks old. Mice that developed a mammary carcinoma were then given weekly intravenous injections of 6 mg/kg doses to determine whether the tumors were susceptible or resistant to Doxil therapy. The monthly injections reduced the incidence of first mammary carcinomas in up to 88-week-old retired breeding C3H/He mice from 65 of 66 (98%) in untreated mice to 22 of 47 (47%) in treated mice. The first 15 mice that developed a mammary tumor while on the prophylactic protocol were then placed on a weekly therapeutic protocol. The therapeutic use of Doxil cured 3 of 15 mice and inhibited the growth of 12 tumors. Drug resistance as a result of treatments was not observed. The mean survival of tumor-bearing mice was extended from 24 days in untreated mice to 87 days in treated mice. Toxic side effects were limited to transient weight loss during the weekly Doxil treatments and to epidermal necrosis and dermal fibrosis due to drug extravasation at the sites of intravenous injections. The authors concluded that doxorubicin in sterically stabilized liposomes deserves to be explored further in comparative studies with free doxorubicin for the prophylaxis and therapy of mammary cancer.

  4. Reproductive experience alters prolactin receptor expression in mammary and hepatic tissues in female rats.

    PubMed

    Bridges, Robert S; Scanlan, Victoria F; Lee, Jong-O; Byrnes, Elizabeth M

    2011-08-01

    Recent studies have reported that reproductive experience in female rats alters prolactin (PRL) receptor gene expression in the brain as well as neural sensitivity to PRL. Given PRL's actions in nonneural tissues, that is, mammary tissue and liver, it was asked whether reproductive experience may also alter prolactin receptor (Prlr) gene expression in these tissues. Groups of age-matched female rats were generated with varying reproductive histories. Separate groups of primiparous (first lactation) and multiparous (second lactation) had mammary tissue and liver samples collected on Day 3 or 10 of lactation. A fifth group raised one litter to weaning and then resumed estrous cyclicity. This group and a final group of age-matched, virgin controls were killed on diestrus. Tissue was processed by quantitative PCR for expression rates of the long and short forms of Prlr mRNA as well as casein beta mRNA (mammary tissue only). Western blots were performed to quantify receptor protein content. Multiple lactations as well as lactation itself resulted in alterations in Prlr expression. Prlr gene expression in mammary tissue was increased in primiparous mothers compared with that in multiparous dams, whereas in the liver, Prlr expression was reduced during an initial lactation. In contrast, PRLR protein levels declined during lactation in mammary, but not hepatic, tissues. Overall, the results demonstrate that the prolactin receptor system is altered in nonneural tissues as a result of the female's reproductive history. The findings are discussed in the context of milk and bile production and PRL's possible role in breast cancer.

  5. PGE2 /EP4 Signaling Controls the Transfer of the Mammary Stem Cell State by Lipid Rafts in Extracellular Vesicles.

    PubMed

    Lin, Meng-Chieh; Chen, Shih-Yin; Tsai, Ho-Min; He, Pei-Lin; Lin, Yen-Chun; Herschman, Harvey; Li, Hua-Jung

    2017-02-01

    Prostaglandin E 2 (PGE 2 )-initiated signaling contributes to stem cell homeostasis and regeneration. However, it is unclear how PGE 2 signaling controls cell stemness. This study identifies a previously unknown mechanism by which PGE 2 /prostaglandin E receptor 4 (EP 4 ) signaling regulates multiple signaling pathways (e.g., PI3K/Akt signaling, TGFβ signaling, Wnt signaling, EGFR signaling) which maintain the basal mammary stem cell phenotype. A shift of basal mammary epithelial stem cells (MaSCs) from a mesenchymal/stem cell state to a non-basal-MaSC state occurs in response to prostaglandin E receptor 4 (EP 4 ) antagonism. EP 4 antagonists elicit release of signaling components, by controlling their trafficking into extracellular vesicles/exosomes in a lipid raft/caveolae-dependent manner. Consequently, EP 4 antagonism indirectly inactivates, through induced extracellular vesicle/exosome release, pathways required for mammary epithelial stem cell homeostasis, e.g. canonical/noncanonical Wnt, TGFβ and PI3K/Akt pathways. EP 4 antagonism causes signaling receptors and signaling components to shift from non-lipid raft fractions to lipid raft fractions, and to then be released in EP 4 antagonist-induced extracellular vesicles/exosomes, resulting in the loss of the stem cell state by mammary epithelial stem cells. In contrast, luminal mammary epithelial cells can acquire basal stem cell properties following ingestion of EP 4 antagonist-induced stem cell extracellular vesicles/exosomes, and can then form mammary glands. These findings demonstrate that PGE 2 /EP 4 signaling controls homeostasis of mammary epithelial stem cells through regulating extracellular vesicle/exosome release. Reprogramming of mammary epithelial cells can result from EP 4 -mediated stem cell property transfer by extracellular vesicles/exosomes containing caveolae-associated proteins, between mammary basal and luminal epithelial cells. Stem Cells 2017;35:425-444. © 2016 The Authors STEM CELLS

  6. Roles of Breast Cancer Susceptibility Genes BRCA’s in Mammary Epithelial Cell Differentiation

    DTIC Science & Technology

    2006-03-01

    1-0322 TITLE: Roles of Breast Cancer Susceptibility Genes BRCA’s in Mammary Epithelial Cell Differentiation PRINCIPAL...Summary 3. DATES COVERED (From - To) 1 MAR 2005 - 28 FEB 2006 4. TITLE AND SUBTITLE Roles of Breast Cancer Susceptibility Genes BRCA’s in Mammary...reverse the phenotype of differentiation-defective breast cancer cells bearing reduced BRCA1 functions. This result implies BRCA1 is involved in

  7. Immunomodulation of Host Chitinase 3-Like 1 During a Mammary Pathogenic Escherichia coli Infection

    PubMed Central

    Breyne, Koen; Steenbrugge, Jonas; Demeyere, Kristel; Lee, Chun Geun; Elias, Jack A.; Petzl, Wolfram; Smith, David G. E.; Germon, Pierre; Meyer, Evelyne

    2018-01-01

    Chitin is a N-acetyl-d-glucosamine biopolymer that can be recognized by chitin-binding proteins. Although mammals lack chitin synthase, they induce proteins responsible for detecting chitin in response to bacterial infections. Our aim was to investigate whether chitinase 3-like 1 (CHI3L1) has a potential role in the innate immunity of the Escherichia coli (E. coli) infected mammary gland. CHI3L1 protein was found to be secreted in whey of naturally coliform-affected quarters compared to whey samples isolated from healthy udders. In addition, gene expression of CHI3L1 was confirmed in udder tissue of cows experimentally infected with a mammary pathogenic E. coli (MPEC) strain. Despite the known anatomical differences, the bovine udders’ innate immune response was mimicked by applying an experimental mouse model using MPEC or non-MPEC isolates. The effect of CHI3L1 expression in the murine mammary gland in response to coliform bacteria was investigated through the use of CHI3L1−/− mice as well as through treatment with either a pan-caspase inhibitor or chitin particles in wild-type mice. The local induction of CHI3L1 postinfection with different E. coli strains was demonstrated to be independent of both bacterial growth and mammary interleukin (IL)-8 levels. Indeed, CHI3L1 emerged as a regulator impacting on the transcytosis of Ly6G-positive cells from the interstitial space into the alveolar lumen of the mammary tissue. Furthermore, CHI3L1 was found to be upstream regulated by caspase activity and had a major downstream effect on the local pro-inflammatory cytokine profile, including IL-1beta, IL-6, and RANTES/CCL5. In conclusion, CHI3L1 was demonstrated to play a key role in the cytokine and caspase signaling during E. coli triggered inflammation of the mammary gland. PMID:29892291

  8. Pleural ultrasonography versus chest radiography for the diagnosis of pneumothorax: review of the literature and meta-analysis.

    PubMed

    Alrajab, Saadah; Youssef, Asser M; Akkus, Nuri I; Caldito, Gloria

    2013-09-23

    Ultrasonography is being increasingly utilized in acute care settings with expanding applications. Pneumothorax evaluation by ultrasonography is a fast, safe, easy and inexpensive alternative to chest radiographs. In this review, we provide a comprehensive analysis of the current literature comparing ultrasonography and chest radiography for the diagnosis of pneumothorax. We searched English-language articles in MEDLINE, EMBASE and Cochrane Library dealing with both ultrasonography and chest radiography for diagnosis of pneumothorax. In eligible studies that met strict inclusion criteria, we conducted a meta-analysis to evaluate the diagnostic accuracy of pleural ultrasonography in comparison with chest radiography for the diagnosis of pneumothorax. We reviewed 601 articles and selected 25 original research articles for detailed review. Only 13 articles met all of our inclusion criteria and were included in the final analysis. One study used lung sliding sign alone, 12 studies used lung sliding and comet tail signs, and 6 studies searched for lung point in addition to the other two signs. Ultrasonography had a pooled sensitivity of 78.6% (95% CI, 68.1 to 98.1) and a specificity of 98.4% (95% CI, 97.3 to 99.5). Chest radiography had a pooled sensitivity of 39.8% (95% CI, 29.4 to 50.3) and a specificity of 99.3% (95% CI, 98.4 to 100). Our meta-regression and subgroup analyses indicate that consecutive sampling of patients compared to convenience sampling provided higher sensitivity results for both ultrasonography and chest radiography. Consecutive versus nonconsecutive sampling and trauma versus nontrauma settings were significant sources of heterogeneity. In addition, subgroup analysis showed significant variations related to operator and type of probe used. Our study indicates that ultrasonography is more accurate than chest radiography for detection of pneumothorax. The results support the previous investigations in this field, add new valuable information

  9. Leukocyte populations and cytokine expression in the mammary gland in a mouse model of Streptococcus agalactiae mastitis.

    PubMed

    Trigo, Gabriela; Dinis, Márcia; França, Angela; Bonifácio Andrade, Elva; Gil da Costa, Rui M; Ferreira, Paula; Tavares, Delfina

    2009-07-01

    Streptococcus agalactiae is a contagious, mastitis-causing pathogen that is highly adapted to survive in the bovine mammary gland. This study used a BALB/c mouse model of Streptococcus agalactiae mastitis to evaluate leukocyte populations in regional lymph nodes and cytokine expression in the mammary gland involved in the immune response against Streptococcus agalactiae. It was found that the bacteria replicated efficiently in the mammary gland, peaking after 24 h and increasing by 100-fold. Dissemination of bacteria to systemic organs was observed 6 h after infection. At the same time, a massive infiltration of polymorphonuclear cells and an increase in the inflammatory cytokines interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha were detected in mammary glands, indicating an early inflammatory response. A decrease in the levels of inflammatory cytokines in mammary glands was observed 72 h after infection, accompanied by an increase in the levels of IL-12 and IL-10, which were related to a gradual decrease in bacterial load. An increase in the number of macrophages and B220(+) lymphocytes and similar increases in both CD4(+) and CD8(+) T cells in regional lymph nodes were observed, being most pronounced 5 days after infection. Moreover, increased levels of anti-Streptococcus agalactiae antibodies in the mammary gland were observed 10 days after infection. Overall, these data suggest that the host exhibits both innate and acquired immune responses in response to Streptococcus agalactiae mastitis.

  10. [Abdominal ultrasonography in patients with diabetes mellitus. Part 1: Liver].

    PubMed

    Jenssen, C; Pietsch, C; Gottschalk, U; Barreiros, A P; Teufel, A; Cui, X W; Dietrich, C F

    2015-04-01

    In patients with diabetes mellitus, abdominal ultrasonography is the appropriate diagnostic technique to detect and to follow-up secondary and accompanying diseases of the liver, the kidneys, the pancreas, the gastrointestinal tract and of abdominal vessels. Moreover, pancreatic and hepatic diseases may be realized which are of etiological importance for diabetes mellitus. Based on a systematic survey of the published literature, this review in 3 parts will describe the value of abdominal ultrasonography in patients with diabetes mellitus. Part 1 deals with the diagnostic relevance and particular findings of ultrasonographic methods in hepatic manifestations and complications of diabetes mellitus. © Georg Thieme Verlag KG Stuttgart · New York.

  11. Type 1 receptor tyrosine kinases are differentially phosphorylated in mammary carcinoma and differentially associated with steroid receptors.

    PubMed Central

    Bacus, S. S.; Chin, D.; Yarden, Y.; Zelnick, C. R.; Stern, D. F.

    1996-01-01

    The neu/erbB-2/HER-2 proto-oncogene is amplified and/or overexpressed in up to 30% of mammary carcinomas and has been variably correlated with poor prognosis. The signaling activity of the encoded receptor tyrosine kinase is regulated by interactions with other type 1 receptors and their ligands. We have used a novel approach, phosphorylation-sensitive anti-Neu antibodies, to quantify signaling by Neu and epidermal growth factor receptor in a panel of frozen sections of mammary carcinoma specimens. We also determined the relationship of Neu, phosphorylated Neu (and epidermal growth factor receptor), and phosphotyrosine to the expression of Neu-related receptors (epidermal growth factor receptor, HER-3, and HER-4) and to prognostic factors (estrogen and progesterone receptor). We found that tyrosine phosphorylation of Neu (and hence signaling activity) is highly variable among mammary carcinomas. Neu and HER-4 were associated with divergent correlates, suggesting that they have profoundly different biological activities. These results have implications for etiology of mammary carcinoma for clinical evaluation of mammary carcinoma patients, and for development of Neu-targeted therapeutic strategies. Images Figure 1 Figure 2 PMID:8579117

  12. Oncogene-Induced Changes in Mammary Cell Fate and EMT in Breast Tumorigenesis

    DTIC Science & Technology

    2015-04-01

    have worked on the project? Name: Lauren Walheim Project Role: Chemistry pre-medicine undergraduate student Researcher Identifier (e.g. ORCID ID...Distribution Unlimited The views, opinions and/or findings contained in this report are those of the author( s ) and should not be construed as an...Examine if IGF1R alters mammary cell fate in vivo and the effect this has on mammary tumorigenesis (months 13-30) ...…………………………………………….......11 2a

  13. Biological Function of Plasma Kallikrein in Mammary Gland Stromal Development and Tumor Metastasis

    DTIC Science & Technology

    2008-03-01

    mammary gland as well as to identify targets of PKal activity during involution. Furthermore, mast cells are required for normal mammary duct branching...litters were generated, and no live homozygous mutant animals were identified . Wild-type and heterozygous mice appeared in nearly all litters, and of...to identify homozygous mutants in utero. F2 litters from heterozygous crosses were analyzed at embryonic day (E) 12, 10.5, 9.5, 8, and 7.5. At E12

  14. Expression of the glutamine metabolism-related proteins glutaminase 1 and glutamate dehydrogenase in canine mammary tumours.

    PubMed

    Ryu, J-E; Park, H-K; Choi, H-J; Lee, H-B; Lee, H-J; Lee, H; Yu, E-S; Son, W-C

    2018-06-01

    Glutamine metabolism is an important metabolic pathway for cancer cell survival, and there is a critical connection between tumour growth and glutamine metabolism. Because of their similarities, canine mammary carcinomas are useful for studying human breast cancer. Accordingly, we investigated the correlations between the expression of glutamine metabolism-related proteins and the pathological features of canine mammary tumours. We performed immunohistochemical and western blot analysis of 39 mammary tumour tissues. In immunohistochemical analysis, the expression of glutaminase 1 (GLS1) in the epithelial region increased according to the histological grade (P < .005). In the stromal region, complex-type tumours displayed significantly higher GLS1 intensity than simple-type tumours. However, glutamate dehydrogenase expression did not show the same tendencies as GLS1. The western blot results were consistent with the immunohistochemical findings. These results suggest that the expression of GLS1 is correlates with clinicopathological factors in canine mammary tumours and shows a similar pattern to human breast cancer. © 2017 John Wiley & Sons Ltd.

  15. Silencing of Kv4.1 potassium channels inhibits cell proliferation of tumorigenic human mammary epithelial cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jang, Soo Hwa; Choi, Changsun; Hong, Seong-Geun

    2009-06-26

    Potassium channel activity has been shown to facilitate cell proliferation in cancer cells. In the present study, the role of Kv4.1 channels in immortal and tumorigenic human mammary epithelial cells was investigated. Kv4.1 protein expression was positively correlated with tumorigenicity. Moreover, transfection with siRNAs targeting Kv4.1 mRNA suppressed proliferation of tumorigenic mammary epithelial cells. Experiments using mRNA isolated from human breast cancer tissues revealed that the level of Kv4.1 mRNA expression varied depending on the stage of the tumor. Kv4.1 protein expression increased during stages T2 and T3 compared to normal tissue. These results demonstrated that Kv4.1 plays a rolemore » in proliferation of tumorigenic human mammary epithelial cells. In addition, elevated Kv4.1 expression may be useful as a diagnostic marker for staging mammary tumors and selective blockers of Kv4.1 may serve to suppress tumor cell proliferation.« less

  16. TFAP2C governs the luminal epithelial phenotype in mammary development and carcinogenesis.

    PubMed

    Cyr, A R; Kulak, M V; Park, J M; Bogachek, M V; Spanheimer, P M; Woodfield, G W; White-Baer, L S; O'Malley, Y Q; Sugg, S L; Olivier, A K; Zhang, W; Domann, F E; Weigel, R J

    2015-01-22

    Molecular subtypes of breast cancer are characterized by distinct patterns of gene expression that are predictive of outcome and response to therapy. The luminal breast cancer subtypes are defined by the expression of estrogen receptor-alpha (ERα)-associated genes, many of which are directly responsive to the transcription factor activator protein 2C (TFAP2C). TFAP2C participates in a gene regulatory network controlling cell growth and differentiation during ectodermal development and regulating ESR1/ERα and other luminal cell-associated genes in breast cancer. TFAP2C has been established as a prognostic factor in human breast cancer, however, its role in the establishment and maintenance of the luminal cell phenotype during carcinogenesis and mammary gland development have remained elusive. Herein, we demonstrate a critical role for TFAP2C in maintaining the luminal phenotype in human breast cancer and in influencing the luminal cell phenotype during normal mammary development. Knockdown of TFAP2C in luminal breast carcinoma cells induced epithelial-mesenchymal transition with morphological and phenotypic changes characterized by a loss of luminal-associated gene expression and a concomitant gain of basal-associated gene expression. Conditional knockout of the mouse homolog of TFAP2C, Tcfap2c, in mouse mammary epithelium driven by MMTV-Cre promoted aberrant growth of the mammary tree leading to a reduction in the CD24(hi)/CD49f(mid) luminal cell population and concomitant gain of the CD24(mid)/CD49f(hi) basal cell population at maturity. Our results establish TFAP2C as a key transcriptional regulator for maintaining the luminal phenotype in human breast carcinoma. Furthermore, Tcfap2c influences development of the luminal cell type during mammary development. The data suggest that TFAP2C has an important role in regulated luminal-specific genes and may be a viable therapeutic target in breast cancer.

  17. Mammary and extramammary Paget's disease*

    PubMed Central

    Lopes, Lauro Lourival; Lopes, Ione Maria Ribeiro Soares; Lopes, Lauro Rodolpho Soares; Enokihara, Milvia M. S. S.; Michalany, Alexandre Osores; Matsunaga, Nobuo

    2015-01-01

    Paget's disease, described by Sir James Paget in 1874, is classified as mammary and extramammary. The mammary type is rare and often associated with intraductal cancer (93-100% of cases). It is more prevalent in postmenopausal women and it appears as an eczematoid, erythematous, moist or crusted lesion, with or without fine scaling, infiltration and inversion of the nipple. It must be distinguished from erosive adenomatosis of the nipple, cutaneous extension of breast carcinoma, psoriasis, atopic dermatitis, contact dermatitis, chronic eczema, lactiferous ducts ectasia, Bowen's disease, basal cell carcinoma, melanoma and intraductal papilloma. Diagnosis is histological and prognosis and treatment depend on the type of underlying breast cancer. Extramammary Paget's disease is considered an adenocarcinoma originating from the skin or skin appendages in areas with apocrine glands. The primary location is the vulvar area, followed by the perianal region, scrotum, penis and axillae. It starts as an erythematous plaque of indolent growth, with well-defined edges, fine scaling, excoriations, exulcerations and lichenification. In most cases it is not associated with cancer, although there are publications linking it to tumors of the vulva, vagina, cervix and corpus uteri, bladder, ovary, gallbladder, liver, breast, colon and rectum. Differential diagnoses are candidiasis, psoriasis and chronic lichen simplex. Histopathology confirms the diagnosis. Before treatment begins, associated malignancies should be investigated. Surgical excision and micrographic surgery are the best treatment options, although recurrences are frequent. PMID:25830993

  18. Effects of Pleurotomy on Respiratory Sequelae after Internal Mammary Artery Harvesting

    PubMed Central

    Iyem, Hikmet; Islamoglu, Fatih; Yagdi, Tahir; Sargin, Murat; Berber, Ozbek; Hamulu, Ahmet; Buket, Suat; Durmaz, Isa

    2006-01-01

    The preservation of pleural integrity during mammary artery harvesting may decrease atelectasis and pleural effusion during the postoperative period. We designed this retrospective study to evaluate the effects on postoperative pulmonary function of pleural integrity versus opened pleura, in patients who receive a left internal mammary artery graft. The study group consisted of 1,141 patients who underwent elective coronary artery bypass grafting. The patients were retrospectively evaluated and divided into 2 groups: those who underwent internal mammary artery harvesting with opened pleura (n=873) or with pleural integrity (n=268). To monitor pleural effusion and atelectasis, chest radiography was performed routinely 1 day before operation and on the 2nd, 5th, and 7th postoperative days. The preoperative, after extubation, and 1st postoperative day values of partial oxygen pressure (PaO2), partial carbon dioxide pressure (PaCO2), and oxygen (O2) saturation were recorded for comparison, as was the hematocrit. The mean age of the patients was 57.4 ± 8.81 years. There were no significant differences between the groups in mean values of PaO2, PaCO2, O2 saturation, and hematocrit after extubation or on the 1st postoperative day. Atelectasis on the 5th and 7th postoperative days, pleural effusion on the 2nd, 5th, and 7th days, and postoperative bleeding were significantly less in the group with preserved pleural integrity. We showed that preservation of pleural integrity during internal mammary artery harvesting decreases postoperative bleeding, pleural effusion, and atelectasis. We conclude that preservation of pleural integrity, when possible, can decrease these postoperative complications of coronary artery bypass grafting. PMID:16878610

  19. Aluminium chloride promotes anchorage-independent growth in human mammary epithelial cells.

    PubMed

    Sappino, André-Pascal; Buser, Raphaële; Lesne, Laurence; Gimelli, Stefania; Béna, Frédérique; Belin, Dominique; Mandriota, Stefano J

    2012-03-01

    Aluminium salts used as antiperspirants have been incriminated as contributing to breast cancer incidence in Western societies. To date, very little or no epidemiological or experimental data confirm or infirm this hypothesis. We report here that in MCF-10A human mammary epithelial cells, a well-established normal human mammary epithelial cell model, long-term exposure to aluminium chloride (AlCl(3) ) concentrations of 10-300 µ m, i.e. up to 100 000-fold lower than those found in antiperspirants, and in the range of those recently measured in the human breast, results in loss of contact inhibition and anchorage-independent growth. These effects were preceded by an increase of DNA synthesis, DNA double strand breaks (DSBs), and senescence in proliferating cultures. AlCl(3) also induced DSBs and senescence in proliferating primary human mammary epithelial cells. In contrast, it had no similar effects on human keratinocytes or fibroblasts, and was not detectably mutagenic in bacteria. MCF-10A cells morphologically transformed by long-term exposure to AlCl(3) display strong upregulation of the p53/p21(Waf1) pathway, a key mediator of growth arrest and senescence. These results suggest that aluminium is not generically mutagenic, but similar to an activated oncogene, it induces proliferation stress, DSBs and senescence in normal mammary epithelial cells; and that long-term exposure to AlCl(3) generates and selects for cells able to bypass p53/p21(Waf1) -mediated cellular senescence. Our observations do not formally identify aluminium as a breast carcinogen, but challenge the safety ascribed to its widespread use in underarm cosmetics. Copyright © 2012 John Wiley & Sons, Ltd.

  20. Accuracy of Ultrasonography and Magnetic Resonance Imaging in the Diagnosis of Placenta Accreta

    PubMed Central

    Riteau, Anne-Sophie; Tassin, Mikael; Chambon, Guillemette; Le Vaillant, Claudine; de Laveaucoupet, Jocelyne; Quéré, Marie-Pierre; Joubert, Madeleine; Prevot, Sophie; Philippe, Henri-Jean; Benachi, Alexandra

    2014-01-01

    Purpose To evaluate the accuracy of ultrasonography and magnetic resonance imaging (MRI) in the diagnosis of placenta accreta and to define the most relevant specific ultrasound and MRI features that may predict placental invasion. Material and Methods This study was approved by the institutional review board of the French College of Obstetricians and Gynecologists. We retrospectively reviewed the medical records of all patients referred for suspected placenta accreta to two university hospitals from 01/2001 to 05/2012. Our study population included 42 pregnant women who had been investigated by both ultrasonography and MRI. Ultrasound images and MRI were blindly reassessed for each case by 2 raters in order to score features that predict abnormal placental invasion. Results Sensitivity in the diagnosis of placenta accreta was 100% with ultrasound and 76.9% for MRI (P = 0.03). Specificity was 37.5% with ultrasonography and 50% for MRI (P = 0.6). The features of greatest sensitivity on ultrasonography were intraplacental lacunae and loss of the normal retroplacental clear space. Increased vascularization in the uterine serosa-bladder wall interface and vascularization perpendicular to the uterine wall had the best positive predictive value (92%). At MRI, uterine bulging had the best positive predictive value (85%) and its combination with the presence of dark intraplacental bands on T2-weighted images improved the predictive value to 90%. Conclusion Ultrasound imaging is the mainstay of screening for placenta accreta. MRI appears to be complementary to ultrasonography, especially when there are few ultrasound signs. PMID:24733409

  1. Reversible Causes in Cardiovascular Collapse at the Emergency Department Using Ultrasonography (REVIVE-US).

    PubMed

    Chua, Mui Teng; Chan, Gene Wh; Kuan, Win Sen

    2017-08-01

    Ultrasonographic evaluation of patients in cardiac arrest is currently not protocolised in the advanced cardiac life support (ACLS) algorithm. Potentially reversible causes may be identified using bedside ultrasonography that is ubiquitous in most emergency departments (EDs). This study aimed to evaluate the incidence of sonographically detectable reversible causes of cardiac arrest by incorporating an ultrasonography protocol into the ACLS algorithm. Secondary objectives include rates of survival to hospital admission, hospital discharge, and 30-day mortality. We conducted a prospective study using bedside ultrasonography to evaluate for potentially reversible causes in patients with cardiac arrest at the ED of National University Hospital, Singapore, regardless of the initial electrocardiogram rhythm. A standardised ultrasonography protocol was performed during the 10-second pulse check window. Between June 2015 and April 2016, 104 patients were recruited, corresponding to 65% of all out-of-hospital cardiac arrest patients conveyed to the ED. Median age was 71 years (interquartile range, 55 to 80) and 71 (68.3%) patients were male. The most common rhythm on arrival was asystole (45.2%). Four (3.8%) patients had ultrasonographic findings suggestive of massive pulmonary embolism while 1 received intravenous thrombolysis and survived until discharge. Pericardial effusion without tamponade was detected in 4 (3.8%) patients and 6 (5.8%) patients had intra-abdominal free fluid. Twenty (19.2%) patients survived until admission, 2 of whom (1.9%) survived to discharge and beyond 30 days. Bedside ultrasonography can be safely incorporated into the ACLS protocol. Detection of any reversible causes may alter management and improve survival in selected patients.

  2. Wnt proteins are self-renewal factors for mammary stem cells and promote their long-term expansion in culture.

    PubMed

    Zeng, Yi Arial; Nusse, Roel

    2010-06-04

    Adult stem cells have the ability to self-renew and to generate specialized cells. Self-renewal is dependent on extrinsic niche factors but few of those signals have been identified. In addition, stem cells tend to differentiate in the absence of the proper signals and are therefore difficult to maintain in cell culture. The mammary gland provides an excellent system to study self-renewal signals, because the organ develops postnatally, arises from stem cells, and is readily generated from transplanted cells. We show here that adult mammary glands contain a Wnt-responsive cell population that is enriched for stem cells. In addition, stem cells mutant for the negative-feedback regulator Axin2 and therefore sensitized to Wnt signals have a competitive advantage in mammary gland reconstitution assays. In cell culture experiments, exposure to purified Wnt protein clonally expands mammary stem cells for many generations and maintains their ability to generate functional glands in transplantation assays. We conclude that Wnt proteins serve as rate-limiting self-renewal signals acting directly on mammary stem cells. Copyright 2010 Elsevier Inc. All rights reserved.

  3. Differences in the Rate of In Situ Mammary Gland Development and Other Developmental Endpoints in Three Strains of Female Rat Commonly Used in Mammary Carcinogenesis Studies: Implications for Timing of Carcinogen Exposure

    PubMed Central

    Stanko, Jason P.; Kissling, Grace E.; Chappell, Vesna A.; Fenton, Suzanne E.

    2016-01-01

    The potential of chemicals to alter susceptibility to mammary tumor formation is often assessed using a carcinogen-induced study design in various rat strains. The rate of mammary gland development must be considered so that the timing of carcinogen administration is impactful. In this study, in situ mammary gland (MG) development was assessed in females of the Harlan Sprague Dawley (Hsd:SD), Charles River Sprague Dawley (Crl:SD), and Charles River Long Evans (Crl:LE) rat strains at postnatal day (PND) 25, 33, and 45. Development was evaluated by physical assessment of growth parameters, developmental scoring, and quantitative morphometric analysis. Though body weight was consistently lower and day of vaginal opening (VO) occurred latest in female Hsd:SD rats, they exhibited accelerated pre-and peripubertal MG development compared to other strains. Glands of Crl:SD and Crl:LE rats exhibited significantly more terminal end buds (TEBs) and TEB/mm than Hsd:SD rats around the time of VO. These data suggest a considerable difference in rate of MG development across commonly used strains, which is independent of body weight and timing of VO. In mammary tumor induction studies employing these strains, administration of the carcinogen should be timed appropriately, based on strain, to specifically target the peak of TEB occurrence. PMID:27613105

  4. Laminin and biomimetic extracellular elasticity enhance functional differentiation in mammary epithelia

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Alcaraz, Jordi; Xu, Ren; Mori, Hidetoshi

    2008-10-20

    In the mammary gland, epithelial cells are embedded in a 'soft' environment and become functionally differentiated in culture when exposed to a laminin-rich extracellular matrix gel. Here, we define the processes by which mammary epithelial cells integrate biochemical and mechanical extracellular cues to maintain their differentiated phenotype. We used single cells cultured on top of gels in conditions permissive for {beta}-casein expression using atomic force microscopy to measure the elasticity of the cells and their underlying substrata. We found that maintenance of {beta}-casein expression required both laminin signalling and a 'soft' extracellular matrix, as is the case in normal tissuesmore » in vivo, and biomimetic intracellular elasticity, as is the case in primary mammary epithelial organoids. Conversely, two hallmarks of breast cancer development, stiffening of the extracellular matrix and loss of laminin signalling, led to the loss of {beta}-casein expression and non-biomimetic intracellular elasticity. Our data indicate that tissue-specific gene expression is controlled by both the tissues unique biochemical milieu and mechanical properties, processes involved in maintenance of tissue integrity and protection against tumorigenesis.« less

  5. Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model.

    PubMed

    Zheng, Ming-Jie; Wang, Jue; Xu, Lu; Zha, Xiao-Ming; Zhao, Yi; Ling, Li-Jun; Wang, Shui

    2015-02-01

    During the past decades, many efforts have been made in mimicking the clinical progress of human cancer in mouse models. Previously, we developed a human breast tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions between "species-specific" mammary microenvironment of human origin and human breast cancer cells. However, detailed evidences are absent. The present study (in vivo, cellular, and molecular experiments) was designed to explore the regulatory role of human mammary microenvironment in the progress of human breast cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were developed for in vivo comparisons. Then, the orthotopic tumor masses from three different mouse models were collected for primary culture. Finally, the biology of primary cultured human breast cancer cells was compared by cellular and molecular experiments. Results of in vivo mouse models indicated that human breast cancer cells grew better in human mammary microenvironment. Cellular and molecular experiments confirmed that primary cultured human breast cancer cells from HB mouse model showed a better proliferative and anti-apoptotic biology than those from SUB to MFP mouse models. Meanwhile, primary cultured human breast cancer cells from HB mouse model also obtained the migratory and invasive biology for "species-specific" tissue metastasis to human tissues. Comprehensive analyses suggest that "species-specific" mammary microenvironment of human origin better regulates the biology of human breast cancer cells in our humanized mouse model of breast cancer, which is more consistent with the clinical progress of human breast cancer.

  6. Alcohol consumption promotes mammary tumor growth and insulin sensitivity

    PubMed Central

    Hong, Jina; Holcomb, Valerie B.; Tekle, Samrawit A.; Fan, Betty; Núñez, Nomelí P.

    2010-01-01

    Epidemiological data show that in women, alcohol has a beneficial effect by increasing insulin sensitivity but also a deleterious effect by increasing breast cancer risk. These effects have not been shown concurrently in an animal model of breast cancer. Our objective is to identify a mouse model of breast cancer whereby alcohol increases insulin sensitivity and promotes mammary tumorigenesis. Our results from the glucose tolerance test and the homeostasis model assessment show that alcohol consumption improved insulin sensitivity. However, alcohol-consuming mice developed larger mammary tumors and developed them earlier than water-consuming mice. In vitro results showed that alcohol exposure increased the invasiveness of breast cancer cells in a dose-dependent manner. Thus, this animal model, an in vitro model of breast cancer, may be used to elucidate the mechanism(s) by which alcohol affects breast cancer. PMID:20202743

  7. A first immunohistochemistry study of transketolase and transketolase-like 1 expression in canine hyperplastic and neoplastic mammary lesions.

    PubMed

    Burrai, Giovanni Pietro; Tanca, Alessandro; Cubeddu, Tiziana; Abbondio, Marcello; Polinas, Marta; Addis, Maria Filippa; Antuofermo, Elisabetta

    2017-01-31

    Canine mammary tumors represent the most common neoplasm in female dogs, and the discovery of cancer biomarkers and their translation to clinical relevant assays is a key requirement in the war on cancer. Since the description of the 'Warburg effect', the reprogramming of metabolic pathways is considered a hallmark of pathological changes in cancer cells. In this study, we investigate the expression of two cancer-related metabolic enzymes, transketolase (TKT) and transketolase-like 1 (TKTL1), involved in the pentose phosphate pathway (PPP), an alternative metabolic pathway for glucose breakdown that could promote cancer by providing the precursors and energy required for rapidly growing cells. TKT and TKTL1 protein expression was investigated by immunohistochemistry in canine normal (N = 6) and hyperplastic glands (N = 3), as well as in benign (N = 11) and malignant mammary tumors (N = 17). TKT expression was higher in hyperplastic lesions and in both benign and malignant tumors compared to the normal mammary gland, while TKTL1 levels were remarkably higher in hyperplastic lesions, simple adenomas and simple carcinomas than in the normal mammary glands (P < 0.05). This study reveals that the expression of a key PPP enzyme varies along the evolution of canine mammary neoplastic lesions, and supports a role of metabolic changes in the development of canine mammary tumors.

  8. The Ets transcription factor Elf5 specifies mammary alveolar cell fate

    PubMed Central

    Oakes, Samantha R.; Naylor, Matthew J.; Asselin-Labat, Marie-Liesse; Blazek, Katrina D.; Gardiner-Garden, Margaret; Hilton, Heidi N.; Kazlauskas, Michael; Pritchard, Melanie A.; Chodosh, Lewis A.; Pfeffer, Peter L.; Lindeman, Geoffrey J.; Visvader, Jane E.; Ormandy, Christopher J.

    2008-01-01

    Hormonal cues regulate mammary development, but the consequent transcriptional changes and cell fate decisions are largely undefined. We show that knockout of the prolactin-regulated Ets transcription factor Elf5 prevented formation of the secretory epithelium during pregnancy. Conversely, overexpression of Elf5 in an inducible transgenic model caused alveolar differentiation and milk secretion in virgin mice, disrupting ductal morphogenesis. CD61+ luminal progenitor cells accumulated in Elf5-deficient mammary glands and were diminished in glands with Elf5 overexpression. Thus Elf5 specifies the differentiation of CD61+ progenitors to establish the secretory alveolar lineage during pregnancy, providing a link between prolactin, transcriptional events, and alveolar development. PMID:18316476

  9. Ability of Ultrasonography in Detection of Different Extremity Bone Fractures; a Case Series Study

    PubMed Central

    Bozorgi, Farzad; Shayesteh Azar, Massoud; Montazer, Seyed Hossein; Chabra, Aroona; Heidari, Seyed Farshad; Khalilian, Alireza

    2017-01-01

    Introduction: Despite radiography being the gold standard in evaluation of orthopedic injuries, using bedside ultrasonography has several potential supremacies such as avoiding exposure to ionizing radiation, availability in pre-hospital settings, being extensively accessible, and ability to be used on the bedside. The aim of the present study is to evaluate the diagnostic accuracy of ultrasonography in detection of extremity bone fractures. Methods: This study is a case series study, which was prospectively conducted on multiple blunt trauma patients, who were 18 years old or older, had stable hemodynamic, Glasgow coma scale 15, and signs or symptoms of a possible extremity bone fracture. After initial assessment, ultrasonography of suspected bones was performed by a trained emergency medicine resident and prevalence of true positive and false negative findings were calculated compared to plain radiology. Results: 108 patients with the mean age of 44.6 ± 20.4 years were studied (67.6% male). Analysis was done on 158 sites of fracture, which were confirmed with plain radiography. 91 (57.6%) cases were suspected to have upper extremity fracture(s) and 67 (42.4%) to have lower ones. The most frequent site of injuries were forearm (36.7%) in upper limbs and leg (27.8%) in lower limbs. Prevalence of true positive and false negative cases for fractures detected by ultrasonography were 59 (64.8%) and 32 (35.52%) for upper and 49 (73.1%) and 18 (26.9%) for lower extremities, respectively. In addition, prevalence of true positive and false negative detected cases for intra-articular fractures were 24 (48%) and 26 (52%), respectively. Conclusion The present study shows the moderate sensitivity (68.3%) of ultrasonography in detection of different extremity bone fractures. Ultrasonography showed the best sensitivity in detection of femur (100%) and humerus (76.2%) fractures, respectively. It had low sensitivity in detection of in intra-articular fractures. PMID:28286822

  10. Ability of Ultrasonography in Detection of Different Extremity Bone Fractures; a Case Series Study.

    PubMed

    Bozorgi, Farzad; Shayesteh Azar, Massoud; Montazer, Seyed Hossein; Chabra, Aroona; Heidari, Seyed Farshad; Khalilian, Alireza

    2017-01-01

    Despite radiography being the gold standard in evaluation of orthopedic injuries, using bedside ultrasonography has several potential supremacies such as avoiding exposure to ionizing radiation, availability in pre-hospital settings, being extensively accessible, and ability to be used on the bedside. The aim of the present study is to evaluate the diagnostic accuracy of ultrasonography in detection of extremity bone fractures. This study is a case series study, which was prospectively conducted on multiple blunt trauma patients, who were 18 years old or older, had stable hemodynamic, Glasgow coma scale 15, and signs or symptoms of a possible extremity bone fracture. After initial assessment, ultrasonography of suspected bones was performed by a trained emergency medicine resident and prevalence of true positive and false negative findings were calculated compared to plain radiology. 108 patients with the mean age of 44.6 ± 20.4 years were studied (67.6% male). Analysis was done on 158 sites of fracture, which were confirmed with plain radiography. 91 (57.6%) cases were suspected to have upper extremity fracture(s) and 67 (42.4%) to have lower ones. The most frequent site of injuries were forearm (36.7%) in upper limbs and leg (27.8%) in lower limbs. Prevalence of true positive and false negative cases for fractures detected by ultrasonography were 59 (64.8%) and 32 (35.52%) for upper and 49 (73.1%) and 18 (26.9%) for lower extremities, respectively. In addition, prevalence of true positive and false negative detected cases for intra-articular fractures were 24 (48%) and 26 (52%), respectively. The present study shows the moderate sensitivity (68.3%) of ultrasonography in detection of different extremity bone fractures. Ultrasonography showed the best sensitivity in detection of femur (100%) and humerus (76.2%) fractures, respectively. It had low sensitivity in detection of in intra-articular fractures.

  11. Ultrasonography in determining pubertal growth and bone age.

    PubMed

    Torenek Ağırman, Kubra; Bilge, Osman Murat; Miloğlu, Özkan

    2018-05-02

    The purpose of this study is to evaluate the compatibility of ultrasonographic data with hand-wrist radiographs taken to determine the extent of pubertal growth and bone age in patients and investigate the usability of ionizing radiation-free ultrasonography instead of conventional radiography. In this study, a total of 120 children from 10 to 17 years old (mean age was 168 months ± 27.5 months) were treated with routine radiographs before orthodontic treatment, and ultrasonographic imaging was performed on the wrists the same day. Researchers examined the phalanges, sesamoid bone, and radial bone distal epiphysis-diaphysis comparatively in each patient by both imaging methods and statistical evaluation. There was no statistically significant difference between conventional radiography and ultrasonography values at 13 points except for PP1 (proximal phalanges of the first finger), PP2 (proximal phalanges of the second finger), and radial epiphysis (p > 0.05). PP1, PP2, and radial epiphysis showed a statistically significant difference (p < 0.05). The CBA (bone age obtained from conventional radiographs) of the females was found to be larger than their CA (chronological age) and their UBA (ultrasonographic bone age). For males; the means of the CBA, UBA and CA values close to each other. In females and males; there was a strong correlation between the CA, the UBA and the CBA (p < 0.01). Ultrasonography gives detailed information about epiphyseal diaphysis relations. It can be used as an alternative to conventional radiography in the detection of bone age and pubertal growth, owing to the absence of ionizing radiation.

  12. The transcriptional co-factor RIP140 regulates mammary gland development by promoting the generation of key mitogenic signals.

    PubMed

    Nautiyal, Jaya; Steel, Jennifer H; Mane, Meritxell Rosell; Oduwole, Olayiwola; Poliandri, Ariel; Alexi, Xanthippi; Wood, Nicholas; Poutanen, Matti; Zwart, Wilbert; Stingl, John; Parker, Malcolm G

    2013-03-01

    Nuclear receptor interacting protein (Nrip1), also known as RIP140, is a co-regulator for nuclear receptors that plays an essential role in ovulation by regulating the expression of the epidermal growth factor-like family of growth factors. Although several studies indicate a role for RIP140 in breast cancer, its role in the development of the mammary gland is unclear. By using RIP140-null and RIP140 transgenic mice, we demonstrate that RIP140 is an essential factor for normal mammary gland development and that it functions by mediating oestrogen signalling. RIP140-null mice exhibit minimal ductal elongation with no side-branching, whereas RIP140-overexpressing mice show increased cell proliferation and ductal branching with age. Tissue recombination experiments demonstrate that RIP140 expression is required in both the mammary epithelial and stromal compartments for ductal elongation during puberty and that loss of RIP140 leads to a catastrophic loss of the mammary epithelium, whereas RIP140 overexpression augments the mammary basal cell population and shifts the progenitor/differentiated cell balance within the luminal cell compartment towards the progenitors. For the first time, we present a genome-wide global view of oestrogen receptor-α (ERα) binding events in the developing mammary gland, which unravels 881 ERα binding sites. Unbiased evaluation of several ERα binding sites for RIP140 co-occupancy reveals selectivity and demonstrates that RIP140 acts as a co-regulator with ERα to regulate directly the expression of amphiregulin (Areg), the progesterone receptor (Pgr) and signal transducer and activator of transcription 5a (Stat5a), factors that influence key mitogenic pathways that regulate normal mammary gland development.

  13. Mammary ductal growth is impaired in mice lacking leptin-dependent signal transducer and activator of transcription 3 signaling.

    PubMed

    Thorn, Stephanie R; Giesy, Sarah L; Myers, Martin G; Boisclair, Yves R

    2010-08-01

    Mice lacking leptin (ob/ob) or its full-length receptor (db/db) are obese and reproductively incompetent. Fertility, pregnancy, and lactation are restored, respectively, in ob/ob mice treated with leptin through mating, d 6.5 post coitum, and pregnancy. Therefore, leptin signaling is needed for lactation, but the timing of its action and the affected mammary process remain unknown. To address this issue, we used s/s mice lacking only leptin-dependent signal transducer and activator of transcription (STAT)3 signaling. These mice share many features with db/db mice, including obesity, but differ by retaining sufficient activity of the hypothalamic-pituitary-ovarian axis to support reproduction. The s/s mammary epithelium was normal at 3 wk of age but failed to expand through the mammary fat pad (MFP) during the subsequent pubertal period. Ductal growth failure was not corrected by estrogen therapy and did not relate to inadequate IGF-I production by the MFP or to the need for epithelial or stromal leptin-STAT3 signaling. Ductal growth failure coincided with adipocyte hypertrophy and increased MFP production of leptin, TNFalpha, and IL6. These cytokines, however, were unable to inhibit the proliferation of a collection of mouse mammary epithelial cell lines. In conclusion, the very first step of postnatal mammary development fails in s/s mice despite sufficient estrogen IGF-I and an hypothalamic-pituitary-ovarian axis capable of supporting reproduction. This failure is not caused by mammary loss of leptin-dependent STAT3 signaling or by the development of inflammation. These data imply the existence of an unknown mechanism whereby leptin-dependent STAT3 signaling and obesity alter mammary ductal development.

  14. MAMMARY GLAND ADENOCARCINOMA IN A MALE BORNEAN ORANGUTAN (PONGO PYGMAEUS).

    PubMed

    Carpenter, Nancy A; Crook, Erika K

    2017-03-01

    An adult male Bornean orangutan ( Pongo pygmaeus ) was diagnosed with invasive, poorly differentiated grade 9/9 mammary gland adenocarcinoma from a subcutaneous mass that was surgically removed during a routine preventative health examination. The tumor was tested for estrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2), and HER2 fluorescence in situ hybridization (HER2 FISH). Whole blood was tested for breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) genes. The orangutan was treated orally with two common human breast cancer drugs; tamoxifen and anastrozole. The orangutan lived for 4.5 yr postdetection, dying from an unrelated cause. This is the first reported case of mammary gland adenocarcinoma in a male great ape.

  15. Assessment of Oropharyngeal Dysphagia in Patients With Parkinson Disease: Use of Ultrasonography.

    PubMed

    Oh, Eun Hyun; Seo, Jin Seok; Kang, Hyo Jung

    2016-04-01

    To compare tongue thickness, the shortest hyoid-thyroid approximation (distance between the hyoid bone and thyroid cartilage), and the time interval between the initiation of tongue movement and the time of the shortest hyoid-thyroid approximation, by using ultrasonography in healthy controls and patients with Parkinson disease (PD). Healthy controls and PD patients with dysphagia were compared. Ultrasonography was performed 3 times for the evaluation of tongue thickness, the shortest hyoid-thyroid approximation, and the time between the initiation of tongue movement and the shortest hyoid-thyroid approximation. A total of 24 healthy controls and 24 PD patients with dysphagia were enrolled. No significant differences were demonstrated between the two groups for the shortest hyoid-thyroid approximation (controls, 1.19±0.34 cm; PD patients, 1.37±0.5 cm; p=0.15) and tongue thickness (controls, 4.42±0.46 cm; PD patients, 4.27±0.51 cm; p=0.3). In contrast, the time to the shortest hyoid-thyroid approximation was significantly different between the two groups (controls, 1.53±0.87 ms; PD patients, 2.4±1.4 ms, p=0.048). Ultrasonography can be useful in evaluating dysphagia in patients with PD by direct visualization and measurement of the hyoid bone. Moreover, ultrasonography might contribute to a greater understanding of the pathophysiology of dysphagia in PD.

  16. A moderate elevation of circulating levels of IGF-I does not alter ErbB2 induced mammary tumorigenesis

    PubMed Central

    2011-01-01

    Background Epidemiological evidence suggests that moderately elevated levels of circulating insulin-like growth factor-I (IGF-I) are associated with increased risk of breast cancer in women. How circulating IGF-I may promote breast cancer incidence is unknown, however, increased IGF-I signaling is linked to trastuzumab resistance in ErbB2 positive breast cancer. Few models have directly examined the effect of moderately high levels of circulating IGF-I on breast cancer initiation and progression. The purpose of this study was to assess the ability of circulating IGF-I to independently initiate mammary tumorigenesis and/or accelerate the progression of ErbB2 mediated mammary tumor growth. Methods We crossed heterozygous TTR-IGF-I mice with heterozygous MMTV-ErbB2 mice to generate 4 different genotypes: TTR-IGF-I/MMTV-ErbB2 (bigenic), TTR-IGF-I only, MMTV-ErbB2 only, and wild type (wt). Virgin females were palpated twice a week and harvested when tumors reached 1000 mm3. For study of normal development, blood and tissue were harvested at 4, 6 and 9 weeks of age in TTR-IGF-I and wt mice. Results TTR-IGF-I and TTR-IGF-I/ErbB2 bigenic mice showed a moderate 35% increase in circulating total IGF-I compared to ErbB2 and wt control mice. Elevation of circulating IGF-I had no effect upon pubertal mammary gland development. The transgenic increase in IGF-I alone wasn't sufficient to initiate mammary tumorigenesis. Elevated circulating IGF-I had no effect upon ErbB2-induced mammary tumorigenesis or metastasis, with median time to tumor formation being 30 wks and 33 wks in TTR-IGF-I/ErbB2 bigenic and ErbB2 mice respectively (p = 0.65). Levels of IGF-I in lysates from ErbB2/TTR-IGF-I tumors compared to ErbB2 was elevated in a similar manner to the circulating IGF-I, however, there was no effect on the rate of tumor growth (p = 0.23). There were no morphological differences in tumor type (solid adenocarcinomas) between bigenic and ErbB2 mammary glands. Conclusion Using the first

  17. Effects of Dietary Xanthophylls, Canthaxanthin and Astaxanthin on N-Methyl-N-nitrosourea-induced Rat Mammary Carcinogenesis.

    PubMed

    Yuri, Takashi; Yoshizawa, Katsuhiko; Emoto, Yuko; Kinoshita, Yuichi; Yuki, Michiko; Tsubura, Airo

    Natural xanthophylls, canthaxanthin and astaxanthin are known to exhibit anticancer activity. However, the dietary effects of canthaxanthin and astaxanthin on N-methyl-N-nitrosourea (MNU)-induced mammary cancer remain controversial, and their mechanisms of action have not been clearly identified. Three-week-old female Sprague-Dawley rats were fed a xanthophyll-free (basal diet) diet or experimental diets containing canthaxanthin or astaxanthin (0.04% and 0.4%) for 5 weeks (until 8 weeks of age), after which all rats were provided the basal diet (n=15 each). Rats were administered MNU at 6 weeks of age, and the incidence of mammary tumors at 20 weeks of age was compared. The expression of adiponectin in mammary adipose tissues taken at 7 weeks of age was also compared. Compared to the basal diet group, the 0.4% (but not the 0.04%) astaxanthin diet significantly reduced the incidence of palpable mammary carcinoma (92% vs. 42%; p<0.05), while the low and high canthaxanthin diets produced no significant inhibition. Adiponectin immunoblotting showed significantly higher expression in the 0.4% astaxanthin diet group, while the other groups were similar to the basal diet group. High concentrations of astaxanthin suppress MNU-induced mammary carcinoma. Changes in adiponectin may be involved in the mechanism of action. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  18. Advanced Imaging Approaches to Characterize Stromal and Metabolic Changes in In Vivo Mammary Tumor Models

    DTIC Science & Technology

    2015-02-01

    Optical imaging , metabolism, tumor microenvironment, NADH, FAD, intravital imaging , collagen, metastasis 3.Overall Project Summary Our preliminary...Keely, KW Eliceiri. Novel Intravital Imaging Approaches to Characterize Collagen Alignment in Defined Mammary Tumor Models. Microscopy and...fixturing for intravital FLIM imaging through a rodent mammary imaging window. Stage is raised to accommodate tall 20xW objective. 14     Figure

  19. Canine mammary minute oncocytomas with neuroendocrine differentiation associated with multifocal acinar cell oncocytic metaplasia.

    PubMed

    Nagahara, Rei; Kimura, Masayuki; Itahashi, Megu; Sugahara, Go; Kawashima, Masashi; Murayama, Hirotada; Yoshida, Toshinori; Shibutani, Makoto

    2016-11-01

    Two solitary and minute tumors of 1 and 1.5 mm diameter were identified by microscopy in the left fourth mammary gland of a 13-year-old female Labrador Retriever dog, in addition to multiple mammary gland tumors. The former tumors were well circumscribed and were composed of small-to-large polyhedral neoplastic oncocytes with finely granular eosinophilic cytoplasm, and were arranged in solid nests separated by fine fibrovascular septa. Scattered lumina of variable sizes containing eosinophilic secretory material were evident. Cellular atypia was minimal, and no mitotic figures were visible. One tumor had several oncocytic cellular foci revealing cellular transition, with perivascular pseudorosettes consisting of columnar epithelial cells surrounding the fine vasculature. Scattered foci of mammary acinar cell hyperplasia showing oncocytic metaplasia were also observed. Immunohistochemically, the cytoplasm of neoplastic cells of the 2 microtumors showed diffuse immunoreactivity to anti-cytokeratin antibody AE1/AE3, and finely granular immunoreactivity for 60-kDa heat shock protein, mitochondrial membrane ATP synthase complex V beta subunit, and chromogranin A. One tumor also had oncocytic cellular foci forming perivascular pseudorosettes showing cellular membrane immunoreactivity for neural cell adhesion molecule. The tumors were negative for smooth muscle actin, neuron-specific enolase, vimentin, desmin, S100, and synaptophysin. Ultrastructural observation confirmed the abundant mitochondria in the cytoplasm of both neoplastic and hyperplastic cells, the former cells also having neuroendocrine granule-like electron-dense bodies. From these results, our case was diagnosed with mammary oncocytomas accompanied by neuroendocrine differentiation. Scattered foci of mammary oncocytosis might be related to the multicentric occurrence of these oncocytomas. © 2016 The Author(s).

  20. Transabdominal ultrasonography as a screening test for second-trimester placenta previa.

    PubMed

    Quant, Hayley S; Friedman, Alexander M; Wang, Eileen; Parry, Samuel; Schwartz, Nadav

    2014-03-01

    To determine the test characteristics of transabdominal ultrasonography as a screening test for second-trimester placenta previa. This secondary analysis of a prospective cohort study evaluated the distance from the placental edge to the internal os (placenta-cervix distance) through both transabdominal and transvaginal ultrasonography during the anatomic survey. Patients were recruited in the Maternal-Fetal Medicine Ultrasound Unit at the Hospital of the University of Pennsylvania, an urban tertiary care center. Transabdominal placenta-cervix distance cutoffs with high sensitivity for detection of previa and low-lying placenta were identified, and test characteristics were calculated. Follow-up ultrasound data, pregnancy, and delivery outcomes for those with second-trimester previa or low-lying placenta were obtained. One thousand two hundred fourteen women were included in the analysis. A transabdominal placenta-cervix distance cutoff of 4.2 cm was 93.3% sensitive and 76.7% specific for detection of previa with a 99.8% negative predictive value at a screen-positive rate of 25.0%. A cutoff of 2.8 cm was 86.7% sensitive and 90.5% specific with a 99.6% negative predictive value at a screen-positive rate of 11.4%. Only 9.8% (four of 41) of previas and low-lying placentas persisted through delivery. Transabdominal ultrasonography is an effective screening test for second-trimester placenta previa. At centers not performing universal transvaginal ultrasonography at the time of the anatomic survey, evidence-based transabdominal placenta-cervix distance cutoffs can optimize the identification of patients who require further surveillance for previa.

  1. The benefits and limitations of using ultrasonography to supplement anatomical understanding.

    PubMed

    Sweetman, Greg M; Crawford, Gail; Hird, Kathryn; Fear, Mark W

    2013-01-01

    Anatomical understanding is critical to medical education. With reduced teaching time and limited cadaver availability, it is important to investigate how best to utilize in vivo imaging to supplement anatomical understanding and better prepare medical graduates for the proliferation of point-of-care imaging in the future. To investigate whether using short sessions of in vivo imaging using ultrasonography could benefit students' anatomical knowledge and clinical application, we conducted a 2-hour session on abdominal anatomy using ultrasonography in small groups of five to six students, for both first- and second-year student cohorts. Individual feedback was collected to assess student perceptions. To measure retention and understanding, a short examination containing ultrasound images and questions and performance of a clinical skill (gastrointestinal' tract examination) were assessed. Ultrasonography sessions were highly valued by the students, with 90% of the students reporting their understanding was improved, and over 70% reporting increased confidence in their anatomical knowledge. However, the assessments showed no appreciable impact on skills or understanding related to abdominal anatomy and examination. We conclude that the risk associated with limited exposure increasing confidence without increasing skills remains real and that in vivo imaging is not effective when used as a short adjunct teaching tool. The widespread use of ultrasonography means finding the best way to incorporate ultrasound into medical education remains important. To this end, we are currently implementing an extended program including echocardiography and multiple anatomical sessions that will determine if frequency and repetition of use can positively impact on student performance and understanding. Copyright © 2012 American Association of Anatomists.

  2. Endovascular repair of an internal mammary artery aneurysm in a patient with SMAD-3 mutation.

    PubMed

    Burke, Chris; Shalhub, Sherene; Starnes, Benjamin W

    2015-08-01

    Aneurysms of the internal mammary artery are rare. We describe a case of a 49-year-old woman with a SMAD3 mutation who presented with left internal mammary artery aneurysm that was thought to have ruptured, causing a large spontaneous left mediastinal hematoma. The aneurysm was treated successfully months after initial presentation with coil embolization. SMAD3 mutations are linked to familial thoracic aortic aneurysms and dissections, peripheral aneurysms, and early-onset osteoarthritis, with an estimated incidence of 2% in families with familial thoracic aortic aneurysms and dissections. To our knowledge, this is the first case in the literature to link a SMAD3 mutation with internal mammary artery aneurysm. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  3. 5-Fluorouracil may enrich cancer stem cells in canine mammary tumor cells in vitro.

    PubMed

    Zhou, Bin; Jin, Yipeng; Zhang, Di; Lin, Degui

    2018-05-01

    Mammary gland carcinomas are the most common neoplasms in women and unsterilized female dogs. Owing to the existence of cancer stem cells (CSCs), chemotherapy is not able to cure these types of diseases completely. A number of studies have demonstrated that CSCs are resistant to chemotherapeutic drugs, but whether canine mammary tumor cells that have acquired resistance to 5-fluorouracil (5-FU) exhibited properties of CSCs remains unknown. The aim of the present study was to investigate whether 5-fluorouracil-resistant canine mammary tumor cells exhibited properties of CSCs. CSCs were analyzed using western blot assays, ultra-low attachment sphere cultures, flow cytometry and migration (wound healing and Transwell) assays. The results indicated that, compared with parental cells, proteins associated with the Wnt/β-catenin signaling pathway and aldehyde dehydrogenase 1 were overexpressed, the number and size of spheres in the 5-FU-resistant cells were increased, the ratio of CD44 + /CD24 -/low cells was increased and the migratory ability was improved in vitro compared with the 5-FU-susceptible cells. In conclusion, stimulation with chemotherapeutic drugs including 5-FU is a good method for increasing the proportion of canine mammary tumor stem cells in vitro , which may provide further understanding of chemotherapeutic methods and CSCs.

  4. Sterol regulatory element-binding proteins are regulators of the sodium/iodide symporter in mammary epithelial cells.

    PubMed

    Wen, G; Pachner, L I; Gessner, D K; Eder, K; Ringseis, R

    2016-11-01

    The sodium/iodide symporter (NIS), which is essential for iodide concentration in the thyroid, is reported to be transcriptionally regulated by sterol regulatory element-binding proteins (SREBP) in rat FRTL-5 thyrocytes. The SREBP are strongly activated after parturition and throughout lactation in the mammary gland of cattle and are important for mammary epithelial cell synthesis of milk lipids. In this study, we tested the hypothesis that the NIS gene is regulated also by SREBP in mammary epithelial cells, in which NIS is functionally expressed during lactation. Regulation of NIS expression and iodide uptake was investigated by means of inhibition, silencing, and overexpression of SREBP and by reporter gene and DNA-binding assays. As a mammary epithelial cell model, the human MCF-7 cell line, a breast adenocarcinoma cell line, which shows inducible expression of NIS by all-trans retinoic acid (ATRA), and unlike bovine mammary epithelial cells, is widely used to investigate the regulation of mammary gland NIS and NIS-specific iodide uptake, was used. Inhibition of SREBP maturation by treatment with 25-hydroxycholesterol (5 µM) for 48h reduced ATRA (1 µM)-induced mRNA concentration of NIS and iodide uptake in MCF-7 cells by approximately 20%. Knockdown of SREBP-1c and SREBP-2 by RNA interference decreased the mRNA and protein concentration of NIS by 30 to 50% 48h after initiating knockdown, whereas overexpression of nuclear SREBP (nSREBP)-1c and nSREBP-2 increased the expression of NIS in MCF-7 cells by 45 to 60%, respectively, 48h after initiating overexpression. Reporter gene experiments with varying length of NIS promoter reporter constructs revealed that the NIS 5'-flanking region is activated by nSREBP-1c and nSREBP-2 approximately 1.5- and 4.5-fold, respectively, and activation involves a SREBP-binding motif (SRE) at -38 relative to the transcription start site of the NIS gene. Gel shift assays using oligonucleotides spanning either the wild-type or the

  5. Epigenetic dysregulation of key developmental genes in radiation-induced rat mammary carcinomas.

    PubMed

    Daino, Kazuhiro; Nishimura, Mayumi; Imaoka, Tatsuhiko; Takabatake, Masaru; Morioka, Takamitsu; Nishimura, Yukiko; Shimada, Yoshiya; Kakinuma, Shizuko

    2018-02-13

    With the increase in the number of long-term cancer survivors worldwide, there is a growing concern about the risk of secondary cancers induced by radiotherapy. Epigenetic modifications of genes associated with carcinogenesis are attractive targets for the prevention of cancer owing to their reversible nature. To identify genes with possible changes in functionally relevant DNA methylation patterns in mammary carcinomas induced by radiation exposure, we performed microarray-based global DNA methylation and expression profiling in γ-ray-induced rat mammary carcinomas and normal mammary glands. The gene expression profiling identified dysregulation of developmentally related genes, including the downstream targets of polycomb repressive complex 2 (PRC2) and overexpression of enhancer of zeste homolog 2, a component of PRC2, in the carcinomas. By integrating expression and DNA methylation profiles, we identified ten hypermethylated and three hypomethylated genes that possibly act as tumor-suppressor genes and oncogenes dysregulated by aberrant DNA methylation; half of these genes encode developmental transcription factors. Bisulfite sequencing and quantitative PCR confirmed the dysregulation of the polycomb-regulated developmentally related transcription-factor genes Dmrt2, Hoxa7, Foxb1, Sox17, Lhx8, Gata3 and Runx1. Silencing of Hoxa7 was further verified by immunohistochemistry. These results suggest that, in radiation-induced mammary gland carcinomas, PRC2-mediated aberrant DNA methylation leads to dysregulation of developmentally related transcription-factor genes. Our findings provide clues to molecular mechanisms linking epigenetic regulation and radiation-induced breast carcinogenesis and underscore the potential of such epigenetic mechanisms as targets for cancer prevention. © 2018 UICC.

  6. Scribble Modulates the MAPK/Fra1 Pathway to Disrupt Luminal and Ductal Integrity and Suppress Tumour Formation in the Mammary Gland

    PubMed Central

    Godde, Nathan J.; Sheridan, Julie M.; Smith, Lorey K.; Pearson, Helen B.; Britt, Kara L.; Galea, Ryan C.; Yates, Laura L.; Visvader, Jane E.; Humbert, Patrick O.

    2014-01-01

    Polarity coordinates cell movement, differentiation, proliferation and apoptosis to build and maintain complex epithelial tissues such as the mammary gland. Loss of polarity and the deregulation of these processes are critical events in malignant progression but precisely how and at which stage polarity loss impacts on mammary development and tumourigenesis is unclear. Scrib is a core polarity regulator and tumour suppressor gene however to date our understanding of Scrib function in the mammary gland has been limited to cell culture and transplantation studies of cell lines. Utilizing a conditional mouse model of Scrib loss we report for the first time that Scrib is essential for mammary duct morphogenesis, mammary progenitor cell fate and maintenance, and we demonstrate a critical and specific role for Scribble in the control of the early steps of breast cancer progression. In particular, Scrib-deficiency significantly induced Fra1 expression and basal progenitor clonogenicity, which resulted in fully penetrant ductal hyperplasia characterized by high cell turnover, MAPK hyperactivity, frank polarity loss with mixing of apical and basolateral membrane constituents and expansion of atypical luminal cells. We also show for the first time a role for Scribble in mammalian spindle orientation with the onset of mammary hyperplasia being associated with aberrant luminal cell spindle orientation and a failure to apoptose during the final stage of duct tubulogenesis. Restoring MAPK/Fra1 to baseline levels prevented Scrib-hyperplasia, whereas persistent Scrib deficiency induced alveolar hyperplasia and increased the incidence, onset and grade of mammary tumours. These findings, based on a definitive genetic mouse model provide fundamental insights into mammary duct maturation and homeostasis and reveal that Scrib loss activates a MAPK/Fra1 pathway that alters mammary progenitor activity to drive premalignancy and accelerate tumour progression. PMID:24852022

  7. Ultrasonography of the male breast.

    PubMed

    Draghi, F; Tarantino, C C; Madonia, L; Ferrozzi, G

    2011-09-01

    The male breast has been insufficiently explored in the medical literature, particularly that dealing with ultrasonography, although this topic is almost as vast and varied as that of the female breast. The purpose of this article is to provide a schematic review of the most frequent breast lesions encountered in males and their sonographic appearances. After a brief introduction on the anatomy of the male breast, the authors review the non-neoplastic (gynecomastia, pseudogynecomastia, cysts, inflammatory diseases, and Mondor disease) and neoplastic (benign and malignant) lesions encountered in this organ.

  8. Ultrasonography of the male breast

    PubMed Central

    Draghi, F.; Tarantino, C.C.; Madonia, L.; Ferrozzi, G.

    2011-01-01

    The male breast has been insufficiently explored in the medical literature, particularly that dealing with ultrasonography, although this topic is almost as vast and varied as that of the female breast. The purpose of this article is to provide a schematic review of the most frequent breast lesions encountered in males and their sonographic appearances. After a brief introduction on the anatomy of the male breast, the authors review the non-neoplastic (gynecomastia, pseudogynecomastia, cysts, inflammatory diseases, and Mondor disease) and neoplastic (benign and malignant) lesions encountered in this organ. PMID:23397020

  9. Active Plasma Kallikrein Localizes to Mast Cells and Regulates Epithelial Cell Apoptosis, Adipocyte Differentiation, and Stromal Remodeling during Mammary Gland Involution*

    PubMed Central

    Lilla, Jennifer N.; Joshi, Ravi V.; Craik, Charles S.; Werb, Zena

    2009-01-01

    The plasminogen cascade of serine proteases directs both development and tumorigenesis in the mammary gland. Plasminogen can be activated to plasmin by urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), and plasma kallikrein (PKal). The dominant plasminogen activator for mammary involution is PKal, a serine protease that participates in the contact activation system of blood coagulation. We observed that the prekallikrein gene (Klkb1) is expressed highly in the mammary gland during stromal remodeling periods including puberty and postlactational involution. We used a variant of ecotin (ecotin-PKal), a macromolecular inhibitor of serine proteases engineered to be highly specific for active PKal, to demonstrate that inhibition of PKal with ecotin-PKal delays alveolar apoptosis, adipocyte replenishment, and stromal remodeling in the involuting mammary gland, producing a phenotype resembling that resulting from plasminogen deficiency. Using biotinylated ecotin-PKal, we localized active PKal to connective tissue-type mast cells in the mammary gland. Taken together, these results implicate PKal as an effector of the plasminogen cascade during mammary development. PMID:19297327

  10. Lauric Acid Stimulates Mammary Gland Development of Pubertal Mice through Activation of GPR84 and PI3K/Akt Signaling Pathway.

    PubMed

    Meng, Yingying; Zhang, Jing; Zhang, Fenglin; Ai, Wei; Zhu, Xiaotong; Shu, Gang; Wang, Lina; Gao, Ping; Xi, Qianyun; Zhang, Yongliang; Liang, Xingwei; Jiang, Qingyan; Wang, Songbo

    2017-01-11

    It has been demonstrated that dietary fat affects pubertal mammary gland development. However, the role of lauric acid (LA) in this process remains unclear. Thus, this study aimed to investigate the effects of LA on mammary gland development in pubertal mice and to explore the underlying mechanism. In vitro, 100 μM LA significantly promoted proliferation of mouse mammary epithelial cell line HC11 by regulating expression of proliferative markers (cyclin D1/3, p21, PCNA). Meanwhile, LA activated the G protein-coupled receptor 84 (GPR84) and PI3K/Akt signaling pathway. In agreement, dietary 1% LA enhanced mammary duct development, increased the expression of GPR84 and cyclin D1, and activated PI3K/Akt in mammary gland of pubertal mice. Furthermore, knockdown of GPR84 or inhibition of PI3K/Akt totally abolished the promotion of HC11 proliferation induced by LA. These results showed that LA stimulated mammary gland development of pubertal mice through activation of GPR84 and PI3K/Akt signaling pathway.

  11. Role of Mammary Prolactin in Carcinogenesis

    DTIC Science & Technology

    1998-10-01

    severity jectives were to 1) demonstrate local expression of both of breast cancer, and treatments that suppress pituitary PRL PRL and PRL receptor, and 2...factors in the haemopoietic system. Immunol Today 14: mammary tumors and effect of antiestrogen treatment on the de- 212-214 velopment and growth of...PRL is stimulated by interleukin-2 (IL-2), is quence analysis of decidual PRL cDNA (103) has established maximal within 6 h of treatment , and is

  12. Use of ultrasonography to make reproductive management decisions

    USDA-ARS?s Scientific Manuscript database

    Transrectal ultrasonography has been available for making management decisions since the mid 1980’s. This technology allows for the real-time visualization of internal structures (i.e. ovary and fetus) that are otherwise difficult to evaluate. The use of this technology in making reproductive manag...

  13. Mechanisms Underlying the Very High Susceptibility of the Immature Mammary Gland to Carcinogenic Initiation.

    DTIC Science & Technology

    1998-07-01

    adducts (DMBA) and alkylating small adducts (NMU)? In vivo cytotoxicity of 3 versus 8 week old F344 mammary gland following exposure to either NMU or...bacteria, but no plaques. Pinpoint mutants and ex- vivo mutations are another problem; when replated, these will produce a combination of clear and...radiation-induced carcinogenesis than is the mature rat mammary gland in an intact 8 week old F344 rat. Dosimetry : Anesthetized rats were irradiated

  14. Vascular access: the impact of ultrasonography

    PubMed Central

    de Almeida, Carlos Eduardo Saldanha

    2016-01-01

    ABSTRACT Vascular punctures are often necessary in critically ill patients. They are secure, but not free of complications. Ultrasonography enhances safety of the procedure by decreasing puncture attempts, complications and costs. This study reviews important publications and the puncture technique using ultrasound, bringing part of the experience of the intensive care unit of the Hospital Israelita Albert Einstein, São Paulo (SP), Brazil, and discussing issues that should be considered in future studies. PMID:28076607

  15. Endoscopic ultrasonography in chronic pancreatitis: a comparative prospective study with conventional ultrasonography, computed tomography, and ERCP.

    PubMed

    Buscail, L; Escourrou, J; Moreau, J; Delvaux, M; Louvel, D; Lapeyre, F; Tregant, P; Frexinos, J

    1995-04-01

    The usefulness and accuracy rate of endoscopic ultrasonography (EUS) in the diagnosis of chronic pancreatitis (CP) were prospectively evaluated in 81 patients with suspected pancreatic disease. All underwent EUS, abdominal ultrasonography (AUS), and computed tomography (CT), and endoscopic retrograde cholangiopancreatography (ERCP) was performed in 55 of the cases. The diagnosis of CP was established in 44 patients (CP group) including 24 with a calcified form. No pancreatic disease was observed in 18 patients (control group), and 19 patients had a pancreatic tumor. In the CP group AUS was less accurate than EUS in visualizing the pancreas, performances of CT scan being identical to EUS in this respect. A good correlation was observed between EUS and ERCP for visualization and measurement of the Wirsung duct. The most significant changes observed by EUS in the CP group were dilatation of the main pancreatic duct, heterogeneous echogenicity of the pancreatic parenchyma, and cysts < 20 mm in size even in noncalcified CP or with normal pancreatograms. Sensitivity of EUS for diagnosis of CP was 88% (AUS, 58%; ERCP, 74%; CT scan, 75%), the specificity being 100% for ERCP and EUS, 95% for CT scan, and 75% for AUS. The good performances of EUS allow early diagnosis of CP in symptomatic patients since heterogeneous echogenicity of the pancreatic parenchyma seems to be almost specifically associated with the disease.

  16. MAMMARY GLAND DEVELOPMENT: EARLY LIFE EFFECTS FROM THE ENVIRONMENT

    EPA Science Inventory

    Mammary Gland Development: Early Life Effects from the Environment

    S.E. Fenton. Reproductive Toxicology Division, National Health and Environmental Effects Laboratory, ORD, U.S. EPA, Research Triangle Park, NC 27711.

    As signs of precocious puberty in girls reach ...

  17. A 3D Fibroblast-Epithelium Co-culture Model for Understanding Microenvironmental Role in Branching Morphogenesis of the Mammary Gland.

    PubMed

    Koledova, Zuzana; Lu, Pengfei

    2017-01-01

    The mammary gland consists of numerous tissue compartments, including mammary epithelium, an array of stromal cells, and the extracellular matrix (ECM). Bidirectional interactions between the epithelium and its surrounding stroma are essential for proper mammary gland development and homeostasis, whereas their deregulation leads to developmental abnormalities and cancer. To study the relationships between the epithelium and the stroma, development of models that could recapitulate essential aspects of these interacting systems in vitro has become necessary. Here we describe a three-dimensional (3D) co-culture assay and show that the addition of fibroblasts to mammary organoid cultures promotes the epithelium to undergo branching morphogenesis, thus allowing the role of the stromal microenvironment to be examined in this essential developmental process.

  18. Diagnostic PET Imaging of Mammary Microcalcifications Using 64Cu-DOTA-Alendronate in a Rat Model of Breast Cancer

    PubMed Central

    Ahrens, Bradley J.; Li, Lin; Ciminera, Alexandra K.; Chea, Junie; Poku, Erasmus; Bading, James R.; Weist, Michael R.; Miller, Marcia M.; Colcher, David M.

    2017-01-01

    The development of improved breast cancer screening methods is hindered by a lack of cancer-specific imaging agents and effective small-animal models to test them. The purpose of this study was to evaluate 64Cu-DOTA-alendronate as a mammary microcalcification-targeting PET imaging agent, using an ideal rat model. Our long-term goal is to develop 64Cu-DOTA-alendronate for the detection and noninvasive differentiation of malignant versus benign breast tumors with PET. Methods: DOTA-alendronate was synthesized, radiolabeled with 64Cu, and administered to normal or tumor-bearing aged, female, retired breeder Sprague–Dawley rats for PET imaging. Mammary tissues were subsequently labeled and imaged with light, confocal, and electron microscopy to verify microcalcification targeting specificity of DOTA-alendronate and elucidate the histologic and ultrastructural characteristics of the microcalcifications in different mammary tumor types. Tumor uptake, biodistribution, and dosimetry studies were performed to evaluate the efficacy and safety of 64Cu-DOTA-alendronate. Results: 64Cu-DOTA-alendronate was radiolabeled with a 98% yield. PET imaging using aged, female, retired breeder rats showed specific binding of 64Cu-DOTA-alendronate in mammary glands and mammary tumors. The highest uptake of 64Cu-DOTA-alendronate was in malignant tumors and the lowest uptake in benign tumors and normal mammary tissue. Confocal analysis with carboxyfluorescein-alendronate confirmed the microcalcification binding specificity of alendronate derivatives. Biodistribution studies revealed tissue alendronate concentrations peaking within the first hour, then decreasing over the next 48 h. Our dosimetric analysis demonstrated a 64Cu effective dose within the acceptable range for clinical PET imaging agents and the potential for translation into human patients. Conclusion: 64Cu-DOTA-alendronate is a promising PET imaging agent for the sensitive and specific detection of mammary tumors as well as

  19. CXCR4 expression in feline mammary carcinoma cells: evidence of a proliferative role for the SDF-1/CXCR4 axis.

    PubMed

    Ferrari, Angelo; Petterino, Claudio; Ratto, Alessandra; Campanella, Chiara; Wurth, Roberto; Thellung, Stefano; Vito, Guendalina; Barbieri, Federica; Florio, Tullio

    2012-03-14

    Mammary tumours frequently develop in female domestic cats being highly malignant in a large percentage of cases. Chemokines regulate many physiological and pathological processes including organogenesis, chemotaxis of inflammatory cells, as well as tumour progression and metastasization. In particular, the chemokine/receptor pair SDF-1/CXCR4 has been involved in the regulation of metastatic potential of neoplastic cells, including breast cancer. The aim of this study was the immunohistochemical defininition of the expression profile of CXCR4 in primary and metastatic feline mammary carcinomas and the evaluation of the role of SDF-1 in feline mammary tumour cell proliferation. A total of 45 mammary surgical samples, including 33 primary tumours (31 carcinomas and 2 adenomas), 6 metastases, and 4 normal mammary tissues were anlyzed. Tumor samples were collected from a total number of 26 animals, as in some cases concurrent occurrence of neoplasm in more than one mammary gland was observed. Tissues were processed for standard histological examination, and all lesions were classified according to the World Health Organization criteria. CXCR4 expression in neoplastic cells was evaluated by immunohistochemistry. The level of CXCR4 immunoreactivity was semi-quantitatively estimated as CXCR4 score evaluating both the number of positive cells and the intensity of staining. Six primary, fibroblast-free primary cultures were obtained from fresh feline mammary carcinomas and characterized by immunofluorescence for CXCR4 and malignant mammary cell marker expression. SDF-1-dependent in vitro proliferative effects were also assayed. CXCR4 expression was observed in 29 out of 31 malignant tissues with a higher CXCR4 score observed in 4 out of 6 metastatic lesions than in the respective primary tumours. In 2 benign lesions analyzed, only the single basaloid adenoma showed a mild positive immunostaining against CXCR4. Normal tissue did not show CXCR4 immunoreactivity. CXCR4 score

  20. Fetal alcohol exposure and mammary tumorigenesis in offspring: role of the estrogen and insulin-like growth factor systems.

    PubMed

    Cohick, Wendie S; Crismale-Gann, Catina; Stires, Hillary; Katz, Tiffany A

    2015-01-01

    Fetal alcohol spectrum disorders affect a significant number of live births each year, indicating that alcohol consumption during pregnancy is an important public health issue. Environmental exposures and lifestyle choices during pregnancy may affect the offspring's risk of disease in adulthood, leading to the idea that a woman's risk of breast cancer may be pre-programmed prior to birth. Exposure of pregnant rats to alcohol increases tumorigenesis in the adult offspring in response to mammary carcinogens. The estrogen and insulin-like growth factor (IGF-I) axes occupy central roles in normal mammary gland development and breast cancer. 17-β estradiol (E2) and IGF-I synergize to regulate formation of terminal end buds and ductal elongation during pubertal development. The intracellular signaling pathways mediated by the estrogen and IGF-I receptors cross-talk at multiple levels through both genomic and non-genomic mechanisms. Several components of the E2 and IGF-I systems are altered in early development in rat offspring exposed to alcohol in utero, therefore, these changes may play a role in the enhanced susceptibility to mammary carcinogens observed in adulthood. Alcohol exposure in utero induces a number of epigenetic alterations in non-mammary tissues in the offspring and other adverse in utero exposures induce epigenetic modifications in the mammary gland. Future studies will determine if fetal alcohol exposure can induce epigenetic modifications in genes that regulate E2/IGF action at key phases of mammary development, ultimately leading to changes in susceptibility to carcinogens.

  1. Transgenes expressing the Wnt-1 and int-2 proto-oncogenes cooperate during mammary carcinogenesis in doubly transgenic mice.

    PubMed Central

    Kwan, H; Pecenka, V; Tsukamoto, A; Parslow, T G; Guzman, R; Lin, T P; Muller, W J; Lee, F S; Leder, P; Varmus, H E

    1992-01-01

    The Wnt-1 and int-2 proto-oncogenes are transcriptionally activated by mouse mammary tumor virus insertion mutations in virus-induced tumors and encode secretory glycoproteins. To determine whether these two genes can cooperate during carcinogenesis, we have crossed two previously characterized lines of transgenic mice to obtain bitransgenic animals carrying both Wnt-1 and int-2 transgenes under the control of the mouse mammary tumor virus long terminal repeat. Mammary carcinomas appear earlier and with higher frequency in the bitransgenic animals, especially the males, than in either parental line. Nearly all bitransgenic males develop mammary neoplasms within 8 months of birth, whereas only 15% of Wnt-1 transgenic males and none of the int-2 transgenic males have tumors. In virgin bitransgenic females, tumors occur approximately 2 months earlier than in their Wnt-1 transgenic siblings; int-2 transgenic females rarely exhibit tumors. Preneoplastic glands from the bitransgenic animals of either sex demonstrate pronounced epithelial hyperplasia similar to that seen in Wnt-1 transgenic virgin females and males, and both transgenes are expressed in the hyperplastic glands and mammary tumors. RNA from the int-2 transgene is more abundant in mammary glands from bitransgenic animals than from int-2 transgenic animals; the increase is associated with high levels of RNA specific for keratin genes 14 and 18, suggesting that Wnt-1-induced epithelial hyperplasia is responsible for the observed increase in expression of the int-2 transgene. Images PMID:1530875

  2. Neuroendocrine carcinoma of the mammary gland in a dog.

    PubMed

    Nakahira, R; Michishita, M; Yoshimura, H; Hatakeyama, H; Takahashi, K

    2015-01-01

    A 10-year-old female border collie was presented with a mass (2 cm diameter) in the fifth mammary gland. The mass was located in the subcutis and the cut surface was grey-white in colour. Microscopically, the mass was composed of tumour cells arranged in nests of various sizes separated by delicate fibrovascular stroma. The tumour cells had small, round hypochromatic nuclei and abundant cytoplasm. Metastases were observed in the inguinal lymph node. Immunohistochemically, most tumour cells expressed cytokeratin (CK) 20, chromogranin A, neuron-specific enolase, synaptophysin and oestrogen receptor-β, but not low molecular weight CK (CAM5.2), p63 and insulin. Ultrastructurally, the tumour cells contained a large number of electron-dense granules corresponding to neuroendocrine granules. Based on these findings, this case was diagnosed as a neuroendocrine carcinoma of the mammary gland. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Modeling and analysis of transport in the mammary glands

    NASA Astrophysics Data System (ADS)

    Quezada, Ana; Vafai, Kambiz

    2014-08-01

    The transport of three toxins moving from the blood stream into the ducts of the mammary glands is analyzed in this work. The model predictions are compared with experimental data from the literature. The utility of the model lies in its potential to improve our understanding of toxin transport as a pre-disposing factor to breast cancer. This work is based on a multi-layer transport model to analyze the toxins present in the breast milk. The breast milk in comparison with other sampling strategies allows us to understand the mass transport of toxins once inside the bloodstream of breastfeeding women. The multi-layer model presented describes the transport of caffeine, DDT and cimetidine. The analysis performed takes into account the unique transport mechanisms for each of the toxins. Our model predicts the movement of toxins and/or drugs within the mammary glands as well as their bioaccumulation in the tissues.

  4. Use of contrast ultrasonography in the diagnosis of metastatic feline visceral haemangiosarcoma.

    PubMed

    Webster, Natalie; Holloway, Andrew

    2008-08-01

    A 12-year-old cat was presented for investigation of weight loss and inappetence. Radiography and conventional grey-scale ultrasonography showed a large mid-body splenic mass. Contrast enhanced ultrasonography of the liver demonstrated a hypoechoic left lateral lobe nodular mass during the peak and late portal-phases of liver enhancement. Histopathology of the splenic mass and hepatic nodular mass confirmed haemangiosarcoma. The use of ultrasound microbubble contrast media in the diagnosis of hepatic metastasis in the cat has not been previously reported in the cat.

  5. c-myc as a mediator of accelerated apoptosis and involution in mammary glands lacking Socs3

    PubMed Central

    Sutherland, Kate D; Vaillant, François; Alexander, Warren S; Wintermantel, Tim M; Forrest, Natasha C; Holroyd, Sheridan L; McManus, Edward J; Schutz, Gunther; Watson, Christine J; Chodosh, Lewis A; Lindeman, Geoffrey J; Visvader, Jane E

    2006-01-01

    Suppressor of cytokine signalling (SOCS) proteins are critical attenuators of cytokine-mediated signalling in diverse tissues. To determine the importance of Socs3 in mammary development, we generated mice in which Socs3 was deleted in mammary epithelial cells. No overt phenotype was evident during pregnancy and lactation, indicating that Socs3 is not a key physiological regulator of prolactin signalling. However, Socs3-deficient mammary glands exhibited a profound increase in epithelial apoptosis and tissue remodelling, resulting in precocious involution. This phenotype was accompanied by augmented Stat3 activation and a marked increase in the level of c-myc. Moreover, induction of c-myc before weaning using an inducible transgenic model recapitulated the Socs3 phenotype, and elevated expression of likely c-myc target genes, E2F-1, Bax and p53, was observed. Our data establish Socs3 as a critical attenuator of pro-apoptotic pathways that act in the developing mammary gland and provide evidence that c-myc regulates apoptosis during involution. PMID:17139252

  6. Regulation of exosome release from mammary epithelial and breast cancer cells - a new regulatory pathway.

    PubMed

    Riches, Andrew; Campbell, Elaine; Borger, Eva; Powis, Simon

    2014-03-01

    Exosomes are small 50-100nm sized extracellular vesicles released from normal and tumour cells and are a source of a new intercellular communication pathway. Tumour exosomes promote tumour growth and progression. What regulates the release and homoeostatic levels of exosomes, in cancer, in body fluids remains undefined. We utilised a human mammary epithelial cell line (HMEC B42) and a breast cancer cell line derived from it (B42 clone 16) to investigate exosome production and regulation. Exosome numbers were quantified using a Nanosight LM10 and measured in culture supernatants in the absence and presence of exosomes in the medium. Concentrated suspensions of exosomes from the normal mammary epithelial cells, the breast cancer cells and bladder cancer cells were used. The interaction of exosomes with tumour cells was also investigated using fluorescently labelled exosomes. Exosome release from normal human mammary epithelial cells and breast cancer cells is regulated by the presence of exosomes, derived from their own cells, in the extracellular environment of the cells. Exosomes from normal mammary epithelial cells also inhibit exosome secretion by breast cancer cells, which occurs in a tissue specific manner. Labelled exosomes from mammary epithelial cells are internalised into the tumour cells implicating a dynamic equilibrium and suggesting a mechanism for feedback control. These data suggest a previously unknown novel feedback regulatory mechanism for controlling exosome release, which may highlight a new therapeutic approach to controlling the deleterious effects of tumour exosomes. This regulatory mechanism is likely to be generic to other tumours. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Bisphenol A Increases Mammary Cancer Risk in Two Distinct Mouse Models of Breast Cancer1

    PubMed Central

    Weber Lozada, Kristen; Keri, Ruth A.

    2011-01-01

    Bisphenol A (BPA) is an industrial plasticizer that leaches from food containers during normal usage, leading to human exposure. Early and chronic exposure to endocrine-disrupting environmental contaminants such as BPA elevates the potential for long-term health consequences. We examined the impact of BPA exposure on fetal programming of mammary tumor susceptibility as well as its growth promoting effects on transformed breast cancer cells in vivo. Fetal mice were exposed to 0, 25, or 250 μg/kg BPA by oral gavage of pregnant dams. Offspring were subsequently treated with the known mammary carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA). While no significant differences in postnatal mammary development were observed, both low- and high-dose BPA cohorts had a statistically significant increase in susceptibility to DMBA-induced tumors compared to vehicle-treated controls. To determine if BPA also promotes established tumor growth, MCF-7 human breast cancer cells were subcutaneously injected into flanks of ovariectomized NCR nu/nu female mice treated with BPA, 17beta-estradiol, or placebo alone or combined with tamoxifen. Both estradiol- and BPA-treated cohorts formed tumors by 7 wk post-transplantation, while no tumors were detected in the placebo cohort. Tamoxifen reversed the effects of estradiol and BPA. We conclude that BPA may increase mammary tumorigenesis through at least two mechanisms: molecular alteration of fetal glands without associated morphological changes and direct promotion of estrogen-dependent tumor cell growth. Both results indicate that exposure to BPA during various biological states increases the risk of developing mammary cancer in mice. PMID:21636739

  8. Reproductive Experience Alters Prolactin Receptor Expression in Mammary and Hepatic Tissues in Female Rats1

    PubMed Central

    Bridges, Robert S.; Scanlan, Victoria F.; Lee, Jong-O; Byrnes, Elizabeth M.

    2011-01-01

    Recent studies have reported that reproductive experience in female rats alters prolactin (PRL) receptor gene expression in the brain as well as neural sensitivity to PRL. Given PRL's actions in nonneural tissues, that is, mammary tissue and liver, it was asked whether reproductive experience may also alter prolactin receptor (Prlr) gene expression in these tissues. Groups of age-matched female rats were generated with varying reproductive histories. Separate groups of primiparous (first lactation) and multiparous (second lactation) had mammary tissue and liver samples collected on Day 3 or 10 of lactation. A fifth group raised one litter to weaning and then resumed estrous cyclicity. This group and a final group of age-matched, virgin controls were killed on diestrus. Tissue was processed by quantitative PCR for expression rates of the long and short forms of Prlr mRNA as well as casein beta mRNA (mammary tissue only). Western blots were performed to quantify receptor protein content. Multiple lactations as well as lactation itself resulted in alterations in Prlr expression. Prlr gene expression in mammary tissue was increased in primiparous mothers compared with that in multiparous dams, whereas in the liver, Prlr expression was reduced during an initial lactation. In contrast, PRLR protein levels declined during lactation in mammary, but not hepatic, tissues. Overall, the results demonstrate that the prolactin receptor system is altered in nonneural tissues as a result of the female's reproductive history. The findings are discussed in the context of milk and bile production and PRL's possible role in breast cancer. PMID:21508351

  9. Obesity-Associated Alterations in Inflammation, Epigenetics, and Mammary Tumor Growth Persist in Formerly Obese Mice.

    PubMed

    Rossi, Emily L; de Angel, Rebecca E; Bowers, Laura W; Khatib, Subreen A; Smith, Laura A; Van Buren, Eric; Bhardwaj, Priya; Giri, Dilip; Estecio, Marcos R; Troester, Melissa A; Hair, Brionna Y; Kirk, Erin L; Gong, Ting; Shen, Jianjun; Dannenberg, Andrew J; Hursting, Stephen D

    2016-05-01

    Using a murine model of basal-like breast cancer, we tested the hypothesis that chronic obesity, an established breast cancer risk and progression factor in women, induces mammary gland epigenetic reprogramming and increases mammary tumor growth. Moreover, we assessed whether the obesity-induced epigenetic and protumor effects are reversed by weight normalization. Ovariectomized female C57BL/6 mice were fed a control diet or diet-induced obesity (DIO) regimen for 17 weeks, resulting in a normal weight or obese phenotype, respectively. Mice on the DIO regimen were then randomized to continue the DIO diet or were switched to the control diet, resulting in formerly obese (FOb) mice with weights comparable with control mice. At week 24, all mice were orthotopically injected with MMTV-Wnt-1 mouse mammary tumor cells. Mean tumor volume, serum IL6 levels, expression of proinflammatory genes in the mammary fat pad, and mammary DNA methylation profiles were similar in DIO and FOb mice and higher than in controls. Many of the genes found to have obesity-associated hypermethylation in mice were also found to be hypermethylated in the normal breast tissue of obese versus nonobese human subjects, and nearly all of these concordant genes remained hypermethylated after significant weight loss in the FOb mice. Our findings suggest that weight normalization may not be sufficient to reverse the effects of chronic obesity on epigenetic reprogramming and inflammatory signals in the microenvironment that are associated with breast cancer progression. Cancer Prev Res; 9(5); 339-48. ©2016 AACR. ©2016 American Association for Cancer Research.

  10. Garlic and associated allyl sulfur components inhibit N-methyl-N-nitrosourea induced rat mammary carcinogenesis.

    PubMed

    Schaffer, E M; Liu, J Z; Green, J; Dangler, C A; Milner, J A

    1996-04-19

    Our previous studies demonstrated that dietary garlic powder supplementation inhibits N-nitrosamine induced DNA alkylation in liver and mammary tissue. The present studies compared the impact of dietary supplementation with garlic powder or two garlic constituents, water-soluble S-allyl cysteine (SAC) and oil-soluble diallyl disulfide (DADS), on the incidence of mammary tumorigenesis induced by N-methyl-N-nitrosourea (MNU). Female Sprague-Dawley rats were fed semi-purified casein based diets with or without supplements of garlic powder(20g/kg), SAC (57 micromol/kg) or DADS (57 micromol/kg) for 2 weeks prior to treatment with MNU (15 mg/kg body wt). Garlic powder, SAC and DADS supplementation significantly delayed the onset of mammary tumors compared to rats receiving the unsupplemented diet. Tumor incidence 23 weeks after MNU treatment was reduced by 76, 41 and 53% in rats fed garlic, SAC and DADS, respectively, compared to controls (P<0.05). Total tumor number was reduced 81, 35 and 65% by these supplements, respectively (P<0.05). In a separate study the quantity of mammary DNA alkylation occurring 3 h after MNU treatment was reduced in rats fed garlic, SAC or DADS (P<0.05). Specifically, O(6)-methylguanine adducts were reduced by 27, 18 and 23% in rats fed supplemental garlic, SAC and DADS, respectively, compared to controls. N(7)-Methylguanine adducts decreased by 48, 22 and 21% respectively, compared to rats fed the control diet. These studies demonstrate that garlic and associated allyl sulfur components, SAC and DADS, are effective inhibitors of MNU-induced mammary carcinogenesis.

  11. Developmental regulation of mitochondrial biogenesis and function in the mouse mammary gland during a prolonged lactation cycle

    USDA-ARS?s Scientific Manuscript database

    The regulation of mitochondrial biogenesis and function in the lactating mammary cell is poorly understood. The goal of this study was to use proteomics to relate temporal changes in mammary cell mitochondrial function during lactation to changes in the proteins that make up this organelle. The hypo...

  12. Effect of increasing amounts of milk replacer powder added to whole milk on postweaning performance, reproduction, glucose metabolism, and mammary fat pad in dairy heifers.

    PubMed

    Lage, C F A; Azevedo, R A; Machado, F S; Campos, M M; Pereira, L G R; Tomich, T R; Carvalho, B C; Alves, B R C; Santos, G B; Brandão, F Z; Coelho, S G

    2017-11-01

    The aim of this study was to evaluate the effects of increasing the total solids (TS) content of liquid feed, by adding increasing amounts of milk replacer powder to whole milk, on age at puberty and postweaning performance, glucose metabolism, and mammary fat pad of dairy heifers. Crossbreed Holstein × Gyr heifers (n = 58) were distributed into 4 different treatments during the preweaning period. Treatments consisted of liquid feeds with TS content of 12.5 (actual TS = 13.5 ± 0.53%; n = 15), 15.0 (actual TS = 16.1 ± 0.03%; n = 15), 17.5 (actual TS = 18.2 ± 0.14%; n = 13), or 20.0% (actual TS = 20.4 ± 0.24%; n = 15), which were provided up to 59 d old. From 60 to 89 d old, the animals received the same starter offered during the preweaning period in addition to corn silage ad libitum starting at 70 d old. From 90 to 104 d old, the animals were adapted to a total mixed ration. At 105 d old, the animals were distributed in 4 paddocks equipped with electronic feed and water bins and were fed the same total mixed ration ad libitum. A period of adaptation to the electronic feed bins occurred from 105 to 119 d old. Feed and water intake and body weight and body frame development were assessed until puberty. Mammary gland evaluations were performed monthly by ultrasonography from 120 d of age until puberty onset. Puberty onset was determined as plasma progesterone concentration greater than 1 ng/mL in 2 consecutive samples collected 7 d apart. The date of puberty onset was recorded as the collection day of the first of these samples. A glucose tolerance test was performed at 280 d of age. The increased TS content of the liquid feed fed during the preweaning period did not affect dry matter intake, performance, age at puberty, glucose metabolism, or mammary gland fat pad at later stages of rearing process. Conversely, hip width and heart girth increased linearly up to 150 and 240 d of age, respectively, as a result of the increased TS concentration of the liquid feed

  13. Advanced Imaging Approaches to Characterize Stromal and Metabolic Changes in in Vivo Mammary Tumor Models

    DTIC Science & Technology

    2014-03-01

    then locks into the microscope stage for extreme stability. Extremely stable intravital images can then be collected with nearly no breathing...Szulczewski, PJ Keely, KW Eliceiri. Novel Intravital Imaging Approaches to Characterize Collagen Alignment in Defined Mammary Tumor Models. Microscopy and...repeated 3 times on different days. 13   Figure 5: New fixturing for intravital FLIM imaging through a rodent mammary imaging window. Stage is raised

  14. Effect of Provider Experience on Clinician-Performed Ultrasonography for Hydronephrosis in Patients With Suspected Renal Colic

    PubMed Central

    Herbst, Meghan K.; Rosenberg, Graeme; Daniels, Brock; Gross, Cary P.; Singh, Dinesh; Molinaro, Annette M.; Luty, Seth; Moore, Christopher L.

    2016-01-01

    Study objective Hydronephrosis is readily visible on ultrasonography and is a strong predictor of ureteral stones, but ultrasonography is a user-dependent technology and the test characteristics of clinician-performed ultrasonography for hydronephrosis are incompletely characterized, as is the effect of ultrasound fellowship training on predictive accuracy. We seek to determine the test characteristics of ultrasonography for detecting hydronephrosis when performed by clinicians with a wide range of experience under conditions of direct patient care. Methods This was a prospective study of patients presenting to an academic medical center emergency department with suspected renal colic. Before computed tomography (CT) results, an emergency clinician performed bedside ultrasonography, recording the presence and degree of hydronephrosis. CT data were abstracted from the dictated radiology report by an investigator blinded to the bedside ultrasonographic results. Test characteristics of bedside ultrasonography for hydronephrosis were calculated with the CT scan as the reference standard, with test characteristics compared by clinician experience stratified into 4 levels: attending physicians with emergency ultrasound fellowship training, attending physicians without emergency ultrasound fellowship training, ultrasound experienced non–attending physician clinicians (at least 2 weeks of ultrasound training), and ultrasound inexperienced non–attending physician clinicians (physician assistants, nurse practitioners, off-service rotators, and first-year emergency medicine residents with fewer than 2 weeks of ultrasound training). Results There were 670 interpretable bedside ultrasonographic tests performed by 144 unique clinicians, 80.9% of which were performed by clinicians directly involved in the care of the patient. On CT, 47.5% of all subjects had hydronephrosis and 47.0% had a ureteral stone. Among all clinicians, ultrasonography had a sensitivity of 72.6% (95

  15. Effect of provider experience on clinician-performed ultrasonography for hydronephrosis in patients with suspected renal colic.

    PubMed

    Herbst, Meghan K; Rosenberg, Graeme; Daniels, Brock; Gross, Cary P; Singh, Dinesh; Molinaro, Annette M; Luty, Seth; Moore, Christopher L

    2014-09-01

    Hydronephrosis is readily visible on ultrasonography and is a strong predictor of ureteral stones, but ultrasonography is a user-dependent technology and the test characteristics of clinician-performed ultrasonography for hydronephrosis are incompletely characterized, as is the effect of ultrasound fellowship training on predictive accuracy. We seek to determine the test characteristics of ultrasonography for detecting hydronephrosis when performed by clinicians with a wide range of experience under conditions of direct patient care. This was a prospective study of patients presenting to an academic medical center emergency department with suspected renal colic. Before computed tomography (CT) results, an emergency clinician performed bedside ultrasonography, recording the presence and degree of hydronephrosis. CT data were abstracted from the dictated radiology report by an investigator blinded to the bedside ultrasonographic results. Test characteristics of bedside ultrasonography for hydronephrosis were calculated with the CT scan as the reference standard, with test characteristics compared by clinician experience stratified into 4 levels: attending physicians with emergency ultrasound fellowship training, attending physicians without emergency ultrasound fellowship training, ultrasound experienced non-attending physician clinicians (at least 2 weeks of ultrasound training), and ultrasound inexperienced non-attending physician clinicians (physician assistants, nurse practitioners, off-service rotators, and first-year emergency medicine residents with fewer than 2 weeks of ultrasound training). There were 670 interpretable bedside ultrasonographic tests performed by 144 unique clinicians, 80.9% of which were performed by clinicians directly involved in the care of the patient. On CT, 47.5% of all subjects had hydronephrosis and 47.0% had a ureteral stone. Among all clinicians, ultrasonography had a sensitivity of 72.6% (95% confidence interval [CI] 65.4% to 78

  16. The effect of dietary zinc - and polyphenols intake on DMBA-induced mammary tumorigenesis in rats

    PubMed Central

    2012-01-01

    Background The aim of the study was to investigate the effect of dietary supplementation with zinc and polyphenol compounds, i.e. resveratrol and genistein, on the effectiveness of chemically induced mammary cancer and the changes in the content of selected elements (Zn, Cu, Mg, Fe, Ca) in tumors as compared with normal tissue of the mammary gland. Methods Female Sprague-Dawley rats were divided into study groups which, apart from the standard diet and DMBA (7,12-dimethyl-1,2- benz[a]anthracene), were treated with zinc ions (Zn) or zinc ions + resveratrol (Zn + resveratrol) or zinc ions + genistein (Zn + genistein) via gavage for a period from 40 days until 20 weeks of age. The ICP-OES (inductively coupled plasma optical emission spectrometry) technique was used to analyze the following elements: magnesium, iron, zinc and calcium. Copper content in samples was estimated in an atomic absorption spectrophotometer. Results Regardless of the diet (standard; Zn; Zn + resveratrol; Zn + genistein), DMBA-induced breast carcinogenesis was not inhibited. On the contrary, in the Zn + resveratrol supplemented group, tumorigenesis developed at a considerably faster rate. On the basis of quantitative analysis of selected elements we found - irrespectively of the diet applied - great accumulation of copper and iron, which are strongly prooxidative, with a simultaneous considerable decrease of the magnesium content in DMBA-induced mammary tumors. The combination of zinc supplementation with resveratrol resulted in particularly large differences in the amount of the investigated elements in tumors as compared with their content in normal tissue. Conclusions Diet supplementation with zinc and polyphenol compounds, i.e. resveratrol and genistein had no effect on the decreased copper level in tumor tissue and inhibited mammary carcinogenesis in the rat. Irrespectively of the applied diet, the development of the neoplastic process in rats resulted in changes of the iron and magnesium

  17. Bisected, complex N-glycans and galectins in mouse mammary tumor progression and human breast cancer

    PubMed Central

    Miwa, Hazuki E; Koba, Wade R; Fine, Eugene J; Giricz, Orsi; Kenny, Paraic A; Stanley, Pamela

    2013-01-01

    Bisected, complex N-glycans on glycoproteins are generated by the glycosyltransferase MGAT3 and cause reduced cell surface binding of galectins. Previously, we showed that MGAT3 reduces growth factor signaling and retards mammary tumor progression driven by the Polyoma middle T antigen (PyMT) expressed in mammary epithelium under the mouse mammary tumor virus (MMTV) promoter. However, the penetrance of the tumor phenotype became variable in mixed FVB/N and C57BL/6 female mice and we therefore investigated a congenic C57BL/6 Mgat3−/−/MMTV-PyMT model. In the absence of MGAT3, C57BL/6 Mgat3−/−/MMTV-PyMT females exhibited accelerated tumor appearance and increased tumor burden, glucose uptake in tumors and lung metastasis. Nevertheless, activation of extracellular signal-regulated kinase (ERK)1/2 or protein kinase B (AKT) was reduced in ∼20-week C57BL/6 MMTV-PyMT tumors lacking MGAT3. Activation of focal adhesion kinase (FAK), protein tyrosine kinase Src, and p38 mitogen-activated protein kinase were similar to that of controls. All the eight mouse galectin genes were expressed in mammary tumors and tumor epithelial cells (TECs), but galectin-2 and -12 were not detected by western analysis in tumors, and galectin-7 was not detected in 60% of the TEC lines. From microarray data reported for human breast cancers, at least 10 galectin and 7 N-glycan N-acetylglucosaminyl (GlcNAc)-transferase (MGAT) genes are expressed in tumor tissue, and expression often varies significantly between different breast cancer subtypes. Thus, in summary, while MGAT3 and bisected complex N-glycans retard mouse mammary tumor progression, genetic background may modify this effect; identification of key galectins that promote mammary tumor progression in mice is not straightforward because all the eight galectin genes are expressed; and high levels of MGAT3, galectin-4, -8, -10, -13 and -14 transcripts correlate with better relapse-free survival in human breast cancer. PMID:24037315

  18. Serotoninergic and Circadian Systems: Driving Mammary Gland Development and Function

    PubMed Central

    Suárez-Trujillo, Aridany; Casey, Theresa M.

    2016-01-01

    Since lactation is one of the most metabolically demanding states in adult female mammals, beautifully complex regulatory mechanisms are in place to time lactation to begin after birth and cease when the neonate is weaned. Lactation is regulated by numerous different homeorhetic factors, all of them tightly coordinated with the demands of milk production. Emerging evidence support that among these factors are the serotonergic and circadian clock systems. Here we review the serotoninergic and circadian clock systems and their roles in the regulation of mammary gland development and lactation physiology. We conclude by presenting our hypothesis that these two systems interact to accommodate the metabolic demands of lactation and thus adaptive changes in these systems occur to maintain mammary and systemic homeostasis through the reproductive cycles of female mammals. PMID:27471474

  19. Mammary gland neoplasia in long-term rodent studies.

    PubMed Central

    Russo, I H; Russo, J

    1996-01-01

    Breast cancer, the most frequent spontaneous malignancy diagnosed in women in the western world, is continuously increasing in incidence in industrialized nations. Although breast cancer develops in women as the result of a combination of external and endogenous factors such as exposure to ionizing radiation, diet, socioeconomic status, and endocrinologic, familial, or genetic factors, no specific etiologic agent(s) or the mechanisms responsible of the disease has been identified as yet. Thus, experimental models that exhibit the same complex interactions are needed for testing various mechanisms and for assessing the carcinogenic potential of given chemicals. Rodent mammary carcinomas represent such a model to a great extent because, in these species, mammary cancer is a multistep complex process that can be induced by either chemicals, radiation, viruses, or genetic factors. Long-term studies in rodent models have been particularly useful for dissecting the initiation, promotion, and progression steps of carcinogenesis. The susceptibility of the rodent mammary gland to develop neoplasms has made this organ a unique target for testing the carcinogenic potential of specific genotoxic chemicals and environmental agents. Mammary tumors induced by indirect- or direct-acting carcinogens such as 7, 12-dimethlbenz(a)anthracene or N-methyl-N-nitrosourea are, in general, hormone dependent adenocarcinomas whose incidence, number of tumors per animal, tumor latency, and tumor type are influenced by the age, reproductive history, and endocarinologic milieu of the host at the time of carcinogen exposure. Rodent models are informative in the absence of human data. They have provided valuable information on the dose and route of administration to be used and optimal host conditions for eliciting maximal tumorigenic response. Studies of the influence of normal gland development on the pathogenesis of chemically induced mammary carcinomas have clarified the role of differentiation

  20. Endoanal ultrasonography in fecal incontinence: Current and future perspectives.

    PubMed

    Albuquerque, Andreia

    2015-06-10

    Fecal incontinence has a profound impact in a patient's life, impairing quality of life and carrying a substantial economic burden due to health costs. It is an underdiagnosed condition because many affected patients are reluctant to report it and also clinicians are usually not alert to it. Patient evaluation with a detailed clinical history and examination is very important to indicate the type of injury that is present. Endoanal ultrasonography is currently the gold standard for sphincter evaluation in fecal incontinence and is a simple, well-tolerated and non-expensive technique. Most studies revealed 100% sensitivity in identifying sphincter defect. It is better than endoanal magnetic resonance imaging for internal anal sphincter defects, equivalent for the diagnosis of external anal sphincter defects, but with a lower capacity for assessment of atrophy of this sphincter. The most common cause of fecal incontinence is anal sphincter injury related to obstetric trauma. Only a small percentage of women are diagnosed with sphincter tears immediately after vaginal delivery, but endoanal ultrasonography shows that one third of these women have occult sphincter defects. Furthermore, in patients submitted to primary repair of these tears, ultrasound revealed a high frequency of persistent sphincter defects after surgery. Three-dimensional endoanal ultrasonography is currently largely used and accepted for sphincter evaluation in fecal incontinence, improving diagnostic accuracy and our knowledge of physiologic and pathological sphincters alterations. Conversely, there is currently no evidence to support the use of elastography in fecal incontinence evaluation.

  1. Lactation-induced WAP-SV40 Tag transgene expression in C57BL/6J mice leads to mammary carcinoma.

    PubMed

    Hüsler, M R; Kotopoulis, K A; Sundberg, J P; Tennent, B J; Kunig, S V; Knowles, B B

    1998-07-01

    Two transgenic lineages were generated by directing the expression of SV40 T antigen to the mammary gland of inbred C57BL/6J mice using the whey acidic protein (WAP) promoter. In one lineage, WAPTag 1, multiparous female mice developed mammary adenocarcinoma with an average latency period of 13 months. The histopathological phenotype was heterogeneous, tumours occurred in a stochastic fashion, normal tissue was located next to neoplastic tissue, the mammary tumours usually developed and were remarkably similar to that observed in human cases. In addition, male and virgin females developed a poorly differentiated SV40 T antigen-positive soft tissue sarcoma, also at 13 months of age. In the other lineage, WAPTag 3, some parous females developed mammary tumours, but most mice succumbed to osteosarcomas arising from the os petrosum at 5.5 to 6 months of age and on necropsy, renal adenocarcinomas were also found. Appearance of these unexpected tumour types demonstrates the non-specific expression of SV40 Tag under the control of the WAP promoter. The expression of SV40 Tag in mammary glands at different stages of development was also examined, and only actively lactating glands were positive. This suggests that the abundant cyclic synthesis of SV40 Tag associated with pregnancy is required for mammary tumorigenesis in these lineages.

  2. [NUCLEAR STRUCTURE IN THE SECRETORY CELLS OF MAMMARY GLANDS IN LACTATING AND NON-LACTATING RATS].

    PubMed

    Tyutina, K V; Skopichev, V G; Bogolyubov, D S; Bogolyubova, I O

    2016-01-01

    The features of structural and functional organization of the main nuclear compartments and distribution of their key molecular components (chromatin-remodeling protein ATRX, RNA polymerase I and II, and the splicing factor SC35) has been studied in the nuclei of mammary gland cells at different functional states. No significant differences between the nuclei of the cells in the lactating and non-lactating mammary glands have been revealed at the ultrastructural level. At the same time, photometric analysis has revealed higher intensity of nucleoplasmic immunofluorescent staining of mammary glands in the lactating animals when antibodies against the proteins ATRX and SC35 were used. Apparently, this observation reflects the changes of the structural and functional status of chromatin as well as the redistribution of splicing factors between the sites of their deposition and transcription.

  3. Electrophysiological examination and high frequency ultrasonography for diagnosis of radial nerve torsion and compression

    PubMed Central

    Shi, Miao; Qi, Hengtao; Ding, Hongyu; Chen, Feng; Xin, Zhaoqin; Zhao, Qinghua; Guan, Shibing; Shi, Hao

    2018-01-01

    Abstract This study aims to evaluate the value of electrophysiological examination and high frequency ultrasonography in the differential diagnosis of radial nerve torsion and radial nerve compression. Patients with radial nerve torsion (n = 14) and radial nerve compression (n = 14) were enrolled. The results of neurophysiological and high frequency ultrasonography were compared. Electrophysiological examination and high-frequency ultrasonography had a high diagnostic rate for both diseases with consistent results. Of the 28 patients, 23 were positive for electrophysiological examination, showing decreased amplitude and decreased conduction velocity of radial nerve; however, electrophysiological examination cannot distinguish torsion from compression. A total of 27 cases showed positive in ultrasound examinations among all 28 cases. On ultrasound images, the nerve was thinned at torsion site whereas thickened at the distal ends of torsion. The diameter and cross-sectional area of torsion or compression determined the nerve damage, and ultrasound could locate the nerve injury site and measure the length of the nerve. Electrophysiological examination and high-frequency ultrasonography can diagnose radial neuropathy, with electrophysiological examination reflecting the neurological function, and high-frequency ultrasound differentiating nerve torsion from compression. PMID:29480857

  4. Cyclic-glycine-proline accelerates mammary involution by promoting apoptosis and inhibiting IGF-1 function.

    PubMed

    Singh-Mallah, Gagandeep; McMahon, Christopher D; Guan, Jian; Singh, Kuljeet

    2017-12-01

    In rodents, post-lactational involution of mammary glands is characterized by the loss of mammary epithelial cells via apoptosis, which is associated with a decline in the expression of insulin-like growth factor-1 (IGF-1). Overexpression of IGF-1 delays involution by inhibiting apoptosis of epithelial cells and preserving the remaining secretory alveoli. Cyclic-glycine-proline (cGP), a metabolite of IGF-1, normalizes IGF-1 function under pathological conditions by regulating the bioavailability of IGF-1. The present study investigated the effect of cGP on the physiological decline in IGF-1 function during post-lactational mammary involution. Rat dams were gavaged with either cGP (3 mg/kg) or saline once per day from post-natal d8-22. Before collecting tissue on post-natal d23, a pair of mammary glands were sealed on d20 (72 hr-engorgement, thus representative of late-involution) and d22 (24 hr-engorgement, thus representative of mid-involution), while the remaining glands were allowed to involute naturally (early-involution). During early-involution, cGP accelerated the loss of mammary cells through apoptosis, resulting in an earlier clearance of intact secretory alveoli compared with the control group. This coincided with an earlier up-regulation of the cell survival factors, Bcl-xl and IGF-1R, in the early-involution cGP glands compared with the control glands. During late-involution, cGP reduced the bioactivity of IGF-1, which was evident through decreased phosphorylation of IGF-1R in the regressed alveoli. Maternal administration of cGP did not alter milk production and composition during early-, peak-, or late-stage of lactation. These data show that cGP accelerates post-lactational involution by promoting apoptosis and the physiological decline in IGF-1 function. © 2017 Wiley Periodicals, Inc.

  5. A Novel Mammary Fat Pad Transplantation Technique to Visualize the Vessel Generation of Vascular Endothelial Stem Cells.

    PubMed

    Yu, Qing Cissy; Song, Wenqian; Lai, Dengwen; Zeng, Yi Arial

    2017-08-03

    Endothelial cells (ECs) are the fundamental building blocks of the vascular architecture and mediate vascular growth and remodeling to ensure proper vessel development and homeostasis. However, studies on endothelial lineage hierarchy remain elusive due to the lack of tools to gain access as well as to directly evaluate their behavior in vivo. To address this shortcoming, a new tissue model to study angiogenesis using the mammary fat pad has been developed. The mammary gland develops mostly in the postnatal stages, including puberty and pregnancy, during which robust epithelium proliferation is accompanied by extensive vascular remodeling. Mammary fat pads provide space, matrix, and rich angiogenic stimuli from the growing mammary epithelium. Furthermore, mammary fat pads are located outside the peritoneal cavity, making them an easily accessible grafting site for assessing the angiogenic potential of exogenous cells. This work also describes an efficient tracing approach using fluorescent reporter mice to specifically label the targeted population of vascular endothelial stem cells (VESCs) in vivo. This lineage tracing method, coupled with subsequent tissue whole-mount microscopy, enable the direct visualization of targeted cells and their descendants, through which the proliferation capability can be quantified and the differentiation commitment can be fate-mapped. Using these methods, a population of bipotent protein C receptor (Procr) expressing VESCs has recently been identified in multiple vascular systems. Procr + VESCs, giving rise to both new ECs and pericytes, actively contribute to angiogenesis during development, homeostasis, and injury repair. Overall, this manuscript describes a new mammary fat pad transplantation and in vivo lineage tracing techniques that can be used to evaluate the stem cell properties of VESCs.

  6. In utero and lactational exposure to vinclozolin and genistein induces genomic changes in the rat mammary gland.

    PubMed

    El Sheikh Saad, H; Toullec, A; Vacher, S; Pocard, M; Bieche, I; Perrot-Applanat, M

    2013-02-01

    Exposure to low doses of environmental estrogens such as bisphenol A and genistein (G) alters mammary gland development. The effects of environmental anti-androgens, such as the fungicide vinclozolin (V), on mammary gland morphogenesis are unknown. We previously reported that perinatal exposure to G, V, and the GV combination causes histological changes in the mammary gland during the peripubertal period, suggesting alterations to the peripubertal hormone response. We now investigate whether perinatal exposure to these compounds alters the gene expression profiles of the developing glands to identify the dysregulated signaling pathways and the underlying mechanisms. G, V, or GV (1 mg/kg body weight per day) was added to diet of Wistar rats, from conception to weaning; female offspring mammary glands were collected at postnatal days (PNDs) 35 and 50. Genes displaying differential expression and belonging to different functional categories were validated by quantitative PCR and immunocytochemistry. At PND35, G had little effect; the slight changes noted were in genes related to morphogenesis. The changes following exposure to V concerned the functional categories associated with development (Cldn1, Krt17, and Sprr1a), carbohydrate metabolism, and steroidogenesis. The GV mixture upregulated genes (Krt17, Pvalb, and Tnni2) involved in muscle development, indicating effects on myoepithelial cells during mammary gland morphogenesis. Importantly, at PND50, cycling females exposed to GV showed an increase in the expression of genes (Csn2, Wap, and Elf5) related to differentiation, consistent with the previously reported abnormal lobuloalveolar development previously described. Thus, perinatal exposure to GV alters the mammary gland hormone response differently at PND35 (puberty) and in animals with established cycles.

  7. Beneficial bacteria stimulate host immune cells to counteract dietary and genetic predisposition to mammary cancer in mice.

    PubMed

    Lakritz, Jessica R; Poutahidis, Theofilos; Levkovich, Tatiana; Varian, Bernard J; Ibrahim, Yassin M; Chatzigiagkos, Antonis; Mirabal, Sheyla; Alm, Eric J; Erdman, Susan E

    2014-08-01

    Recent studies suggest health benefits including protection from cancer after eating fermented foods such as probiotic yogurt, though the mechanisms are not well understood. Here we tested mechanistic hypotheses using two different animal models: the first model studied development of mammary cancer when eating a Westernized diet, and the second studied animals with a genetic predilection to breast cancer. For the first model, outbred Swiss mice were fed a Westernized chow putting them at increased risk for development of mammary tumors. In this Westernized diet model, mammary carcinogenesis was inhibited by routine exposure to Lactobacillus reuteri ATCC-PTA-6475 in drinking water. The second model was FVB strain erbB2 (HER2) mutant mice, genetically susceptible to mammary tumors mimicking breast cancers in humans, being fed a regular (non-Westernized) chow diet. We found that oral supplement with these purified lactic acid bacteria alone was sufficient to inhibit features of mammary neoplasia in both models. The protective mechanism was determined to be microbially-triggered CD4+CD25+ lymphocytes. When isolated and transplanted into other subjects, these L. reuteri-stimulated lymphocytes were sufficient to convey transplantable anti-cancer protection in the cell recipient animals. These data demonstrate that host immune responses to environmental microbes significantly impact and inhibit cancer progression in distal tissues such as mammary glands, even in genetically susceptible mice. This leads us to conclude that consuming fermentative microbes such as L. reuteri may offer a tractable public health approach to help counteract the accumulated dietary and genetic carcinogenic events integral in the Westernized diet and lifestyle. © 2013 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

  8. Humanization of the mouse mammary gland by replacement of the luminal layer with genetically engineered preneoplastic human cells.

    PubMed

    Verbeke, Stephanie; Richard, Elodie; Monceau, Elodie; Schmidt, Xenia; Rousseau, Benoit; Velasco, Valerie; Bernard, David; Bonnefoi, Herve; MacGrogan, Gaetan; Iggo, Richard D

    2014-12-20

    The cell of origin for estrogen receptor α-positive (ERα+) breast cancer is probably a luminal stem cell in the terminal duct lobular units. To model these cells, we have used the murine myoepithelial layer in the mouse mammary ducts as a scaffold upon which to build a human luminal layer. To prevent squamous metaplasia, a common artifact in genetically-engineered breast cancer models, we sought to limit activation of the epidermal growth factor receptor (EGFR) during in vitro cell culture before grafting the cells. Human reduction mammoplasty cells were grown in vitro in WIT medium. Epidermal growth factor in the medium was replaced with amphiregulin and neuregulin to decrease activation of EGFR and increase activation of EGFR homologs 3 and 4 (ERBB3 and ERBB4). Lentiviral vectors were used to express oncogenic transgenes and fluorescent proteins. Human mammary epithelial cells were mixed with irradiated mouse fibroblasts and Matrigel, then injected through the nipple into the mammary ducts of immunodeficient mice. Engrafted cells were visualized by stereomicroscopy for fluorescent proteins and characterized by histology and immunohistochemistry. Growth of normal mammary epithelial cells in conditions favoring ERBB3/4 signaling prevented squamous metaplasia in vitro. Normal human cells were quickly lost after intraductal injection, but cells infected with lentiviruses expressing CCND1, MYC, TERT, BMI1 and a short-hairpin RNA targeting TP53 were able to engraft and progressively replace the luminal layer in the mouse mammary ducts, resulting in the formation of an extensive network of humanized ducts. Despite expressing multiple oncogenes, the human cells formed a morphologically normal luminal layer. Expression of a single additional oncogene, PIK3CA-H1047R, converted the cells into invasive cancer cells. The resulting tumors were ERα+, Ki67+ luminal B adenocarcinomas that were resistant to treatment with fulvestrant. Injection of preneoplastic human mammary

  9. An unanticipated diagnosis with bedside ultrasonography in patients with acute abdominal pain: rectus hematoma.

    PubMed

    Ünlüer, Erden Erol; Kaykısız, Eylem Kuday

    2017-01-01

    Although abdominal pain is a common presentation in emergency departments, rectus sheath hematoma (RSH) is among the rarest diagnosis. Here we present 2 cases of RSH likely caused by coughing due to upper respiratory tract infection. The two described cases were diagnosed by bedside ultrasonography and confirmed as RSH by computed tomography. Review of patient history and use of ultrasonography are important to avoid misdiagnosisof RSH.

  10. Xanthosine administration does not affect the proportion of epithelial stem cells in bovine mammary tissue, but has a latent negative effect on cell proliferation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rauner, Gat, E-mail: gat.rauner@mail.huji.ac.il; The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem; Barash, Itamar, E-mail: itamar.barash@mail.huji.ac.il

    The challenge in manipulating the proportion of somatic stem cells lies in having to override tissue homeostasis. Xanthosine infusion via the teat canal has been reported to augment the number of label-retaining cells in the mammary gland of 3-month-old bovine calves. To further delineate xanthosine's effect on defined stem cells in the mammary gland of heifers—which are candidates for increased prospective milk production following such manipulation—bovine mammary parenchymal tissue was transplanted and integrated into the cleared mammary fat pad of immunodeficient mice. Xanthosine administration for 14 days did not affect the number of label-retaining cells after 10- and 11-week chases.more » No change in stem cell proportion, analyzed according to CD49f and CD24 expression, was noted. Clone formation and propagation rate of cultured cells, as well as expression of stem cell markers, were also unaffected. In contrast, a latent 50% decrease in bovine mammary cell proliferation rate was observed 11 weeks after xanthosine administration. Tumor development in mice was also limited by xanthosine administration. These effects may have resulted from an initial decrease in expression of the rate-limiting enzyme in guanine synthesis, IMPDH. The data indicate that caution should be exerted when considering xanthosine for stem cell manipulation. - Highlights: • Novel “bovinized“ mouse model for exogenous effects on bovine mammary gland. • Xanthosine did not affect stem cell number/function in bovine mammary gland. • Xanthosine caused an immediate decrease in IMPDH expression in bovine mammary gland. • Xanthosine had latent negative effect on cell proliferation in bovine mammary gland. • Xanthosine administration limited mammary tumor growth.« less

  11. Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent

    PubMed Central

    Cardiff, Robert D.; Trott, Josephine F.; Hovey, Russell C.; Hubbard, Neil E.; Engelberg, Jesse A.; Tepper, Clifford G.; Willis, Brandon J.; Khan, Imran H.; Ravindran, Resmi K.; Chan, Szeman R.; Schreiber, Robert D.; Borowsky, Alexander D.

    2015-01-01

    Female 129:Stat1-null mice (129S6/SvEvTac-Stat1tm1Rds homozygous) uniquely develop estrogen-receptor (ER)-positive mammary tumors. Herein we report that the mammary glands (MG) of these mice have altered growth and development with abnormal terminal end buds alongside defective branching morphogenesis and ductal elongation. We also find that the 129:Stat1-null mammary fat pad (MFP) fails to sustain the growth of 129S6/SvEv wild-type and Stat1-null epithelium. These abnormalities are partially reversed by elevated serum progesterone and prolactin whereas transplantation of wild-type bone marrow into 129:Stat1-null mice does not reverse the MG developmental defects. Medium conditioned by 129:Stat1-null epithelium-cleared MFP does not stimulate epithelial proliferation, whereas it is stimulated by medium conditioned by epithelium-cleared MFP from either wild-type or 129:Stat1-null females having elevated progesterone and prolactin. Microarrays and multiplexed cytokine assays reveal that the MG of 129:Stat1-null mice has lower levels of growth factors that have been implicated in normal MG growth and development. Transplanted 129:Stat1-null tumors and their isolated cells also grow slower in 129:Stat1-null MG compared to wild-type recipient MG. These studies demonstrate that growth of normal and neoplastic 129:Stat1-null epithelium is dependent on the hormonal milieu and on factors from the mammary stroma such as cytokines. While the individual or combined effects of these factors remains to be resolved, our data supports the role of STAT1 in maintaining a tumor-suppressive MG microenvironment. PMID:26075897

  12. Failure of pre-natal ultrasonography to prevent urinary infection associated with underlying urological abnormalities.

    PubMed

    Lakhoo, K; Thomas, D F; Fuenfer, M; D'Cruz, A J

    1996-06-01

    To analyse the reasons underlying the failure of routine pre-natal ultrasonography to prevent the subsequent development of urinary tract infection (UTI) in children with predisposing urological abnormalities. This retrospective study comprised 39 children (22 females and 17 males) who had at least one documented UTI, the presence of an anatomical anomaly of the urinary tract recognized as predisposing to UTI and had undergone ultrasonography of the urinary tract undertaken in fetal life as part of routine maternal ante-natal ultrasonography. Four categories of patients were defined: Group A, those with normal findings on pre-natal ultrasonography and no urological abnormality detected; Group B, those with a urological abnormality detected but where there was a subsequent failure of communication among clinicians; Group C, those with a urological abnormality but who received inappropriate or sub-optimal post-natal management and; Group D, those with a urological abnormality but who had a UTI despite appropriate post-natal management. In each case, the most severe documented episode of UTI was categorized as: Grade I, asymptomatic bacteriuria; Grade II, mild/moderate symptomatic UTI and; Grade III, severe symptomatic UTI necessitating hospital admission. Group A comprised 22 (56%), Group B three (9%), Group C two (5%) and Group D 12 children (31%). Of the 22 children in Group A, nine experienced a UTI of sufficient severity to necessitate hospital admission. Of the 12 children in Group D only one required hospital admission. The failure of pre-natal ultrasonography to identify the underlying predisposing urological abnormality was the most important factor contributing to subsequent UTI in post-natal life. Failure of communication and inappropriate post-natal management were numerically unimportant. In some children, UTI occurred despite pre-natal detection of their underlying anomaly and appropriate post-natal management. However, in this group the UTI was less

  13. GosB Inhibits Triacylglycerol Synthesis and Promotes Cell Survival in Mouse Mammary Epithelial Cells.

    PubMed

    Xu, Gaoxiao; Duan, Saixing; Hou, Jianye; Wei, Zhongxin; Zhao, Guangwei

    2017-01-01

    It has been demonstrated that the activator protein related transcription factor Finkel-Biskis-Jinkins murine osteosarcoma B (GosB) is involved in preadipocyte differentiation and triacylglycerol synthesis. However, the role of GosB in regulating the synthesis of milk fatty acid in mouse mammary glands remains unclear. This research uncovered potentially new roles of GosB in suppressing milk fatty acid synthesis. Results revealed that GosB had the highest expression in lung tissue and showed a higher expression level during nonlactation than during lactation. GosB inhibited the expression of fatty acid synthase (FASN) , stearoyl-CoA desaturase (SCD) , fatty acid binding protein 4 (FABP4) , diacylglycerol acyltransferase 1 (DGAT1) , perilipin 2 (PLIN2) , perilipin 3 (PLIN3) , and C/EBPα in mouse mammary gland epithelial cells (MEC). In addition, GosB reduced cellular triglyceride content and the accumulation of lipid droplets; in particular, GosB enhanced saturated fatty acid concentration (C16:0 and C18:0). The PPAR γ agonist, rosiglitazone (ROSI), promoted apoptosis and inhibited cell proliferation. GosB increased the expression of Bcl-2 and protected MEC from ROSI-induced apoptosis. Furthermore, MECs were protected from apoptosis through the GosB regulation of intracellular calcium concentrations. These findings suggest that GosB may regulate mammary epithelial cells milk fat synthesis and apoptosis via PPAR γ in mouse mammary glands.

  14. [The diagnostic value of ultrasonic elastography and ultrasonography comprehensive score in cervical lesions].

    PubMed

    Lu, R; Xiao, Y

    2017-07-18

    Objective: To evaluate the clinical value of ultrasonic elastography and ultrasonography comprehensive scoring method in the diagnosis of cervical lesions. Methods: A total of 116 patients were selected from the Department of Gynecology of the first hospital affiliated with Central South University from March 2014 to September 2015.All of the lesions were preoperatively examined by Doppler Ultrasound and elastography.The elasticity score was determined by a 5-point scoring method. Calculation of the strain ratio was based on a comparison of the average strain measured in the lesion with the adjacent tissue of the same depth, size, and shape.All these ultrasonic parameters were quantified, added, and arrived at ultrasonography comprehensive scores.To use surgical pathology as the gold standard, the sensitivity, specificity, accuracy of Doppler Ultrasound, elasticity score and strain ratio methods and ultrasonography comprehensive scoring method were comparatively analyzed. Results: (1) The sensitivity, specificity, and accuracy of Doppler Ultrasound in diagnosing cervical lesions were 82.89% (63/76), 85.0% (34/40), and 83.62% (97/116), respectively.(2) The sensitivity, specificity, and accuracy of the elasticity score method were 77.63% (59/76), 82.5% (33/40), and 79.31% (92/116), respectively; the sensitivity, specificity, and accuracy of the strain ratio measure method were 84.21% (64/76), 87.5% (35/40), and 85.34% (99/116), respectively.(3) The sensitivity, specificity, and accuracy of ultrasonography comprehensive scoring method were 90.79% (69/76), 92.5% (37/40), and 91.38% (106/116), respectively. Conclusion: (1) It was obvious that ultrasonic elastography had certain diagnostic value in cervical lesions. Strain ratio measurement can be more objective than elasticity score method.(2) The combined application of ultrasonography comprehensive scoring method, ultrasonic elastography and conventional sonography was more accurate than single parameter.

  15. Cooperative Interactions During Human Mammary Epithelial Cell Immortalization

    DTIC Science & Technology

    2005-07-01

    papilloma virus 16 E6 or E7. Proc. Nat. Acad. Sci. USA, 92: 3687-3691, 1995. 6. Huschtscha, L. I., Neumann, A. A., Noble, J. R., and Reddel, R. R. Effects...Oncology, In press. 5. Wazer, D. E., Liu, X.-L., Chu, Q., Gao, Q., and Band, V. Immortalization of distinct human mammary epithelial cell types by human

  16. Inhibition of benzo(a)pyrene-induced mammary carcinogenesis by retinyl acetate. [Rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    McCormick, D.L.; Burns, F.J.; Albert, R.E.

    1981-03-01

    The administration of a 250-ppM retinyl acetate dietary supplement for various periods relative to intragastric administration of 50 mg benzo(a)pyrene (BP) significantly inhibited the induction of mammary cancers in virgin female inbred LEW/Mai rats. With day of BP administration taken as time 0, groups receiving the retinoid from weeks -2 to +1, +1 to +90, +20 to +90, and -2 to +90 showed a significant reduction in tumor response as compared to controls. The inhibition of carcinogenesis achieved by a +1 to +20 administration schedule was temporary. A 2-week exposure to supplemental retinyl acetate significantly reduced the mammary gland parenchymalmore » cell labeling index in ductal, alveolar, and terminal end bud structures. Beginning the retinyl acetate supplement 1 week after the administration of BP significantly reduced the number of terminal ductal hyperplasias. The inhibition of carcinogenesis achieved by a short period of retinyl acetate administration before and during the period of carcinogen availability as well as the inhibition achieved by long-term postcarcinogen retinoid exposure may involve an antiproliferative effect on the rat mammary gland.« less

  17. Comparison of the accuracy of radiography and ultrasonography for detection of articular lesions in horses.

    PubMed

    Hinz, Antje; Fischer, Andrew T

    2011-10-01

    To compare the accuracy of ultrasonographic and radiographic examination for evaluation of articular lesions in horses. Cross-sectional study. Horses (n = 137) with articular lesions. Radiographic and ultrasonographic examinations of the affected joint(s) were performed before diagnostic or therapeutic arthroscopic surgery. Findings were recorded and compared to lesions identified during arthroscopy. In 254 joints, 432 lesions were identified by arthroscopy. The overall accuracy was 82.9% for ultrasonography and 62.2% for radiography (P < .0001) with a sensitivity of 91.4% for ultrasonography and 66.7% for radiography (P < .0001). The difference in specificity was not statistically significant (P = .2628). The negative predictive value for ultrasonography was 31.5% and 13.2% for radiography (P = .0022), the difference for the positive predictive value was not statistically significant (P = .3898). The accuracy for ultrasonography and radiography for left versus right joints was equal and corresponded with the overall results. Ultrasonographic evaluation of articular lesions was more accurate than radiographic evaluation. © Copyright 2011 by The American College of Veterinary Surgeons.

  18. Pomegranate exerts chemoprevention of experimentally induced mammary tumorigenesis by suppression of cell proliferation and induction of apoptosis.

    PubMed

    Bishayee, Anupam; Mandal, Animesh; Bhattacharyya, Piyali; Bhatia, Deepak

    2016-01-01

    Breast cancer is the second leading cause of cancer-related death in women in the United States and discovery and development of safe chemopreventive drugs is urgently needed. The fruit pomegranate (Punica granatum) is gaining importance because of its various health benefits. This study was initiated to investigate chemopreventive potential of a pomegranate emulsion (PE) against 7,12-dimethylbenz(a)anthracene (DMBA) rat mammary carcinogenesis. The animals were orally administered with PE (0.2-5.0 g/kg), starting 2 wk before and 16 wk following DMBA treatment. PE exhibited a striking reduction of DMBA-induced mammary tumor incidence, total tumor burden, and reversed histopathological changes. PE dose-dependently suppressed cell proliferation and induced apoptosis in mammary tumors. Immunohistochemical studies showed that PE increased intratumor Bax, decreased Bcl2 and manifested a proapoptotic shift in Bax/Bcl2 ratio. In addition, our gene expression study showed PE-mediated upregulation of Bad, caspase-3, caspase-7, caspase-9, poly (ADP ribose) polymerase and cytochrome c in mammary tumors. Thus, PE exerts chemoprevention of mammary carcinogenesis by suppressing cell proliferation and inducing apoptosis mediated through upregulation of Bax and downregulation of Bcl2 in concert with caspase cascades. Pomegranate bioactive phytoconstituents could be developed as a chemopreventive drug to reduce the risk of breast cancer.

  19. Prenatal Exposure to Unconventional Oil and Gas Operation Chemical Mixtures Altered Mammary Gland Development in Adult Female Mice.

    PubMed

    Sapouckey, Sarah A; Kassotis, Christopher D; Nagel, Susan C; Vandenberg, Laura N

    2018-03-01

    Unconventional oil and gas (UOG) operations, which combine hydraulic fracturing (fracking) and directional drilling, involve the use of hundreds of chemicals, including many with endocrine-disrupting properties. Two previous studies examined mice exposed during early development to a 23-chemical mixture of UOG compounds (UOG-MIX) commonly used or produced in the process. Both male and female offspring exposed prenatally to one or more doses of UOG-MIX displayed alterations to endocrine organ function and serum hormone concentrations. We hypothesized that prenatal UOG-MIX exposure would similarly disrupt development of the mouse mammary gland. Female C57Bl/6 mice were exposed to ~3, ~30, ~ 300, or ~3000 μg/kg/d UOG-MIX from gestational day 11 to birth. Although no effects were observed on the mammary glands of these females before puberty, in early adulthood, females exposed to 300 or 3000 μg/kg/d UOG-MIX developed more dense mammary epithelial ducts; females exposed to 3 μg/kg/d UOG-MIX had an altered ratio of apoptosis to proliferation in the mammary epithelium. Furthermore, adult females from all UOG-MIX-treated groups developed intraductal hyperplasia that resembled terminal end buds (i.e., highly proliferative structures typically seen at puberty). These results suggest that the mammary gland is sensitive to mixtures of chemicals used in UOG production at exposure levels that are environmentally relevant. The effect of these findings on the long-term health of the mammary gland, including its lactational capacity and its risk of cancer, should be evaluated in future studies. Copyright © 2018 Endocrine Society.

  20. Mammary gland tumors in irradiated and untreated guinea pigs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hoch-Ligeti, C.; Liebelt, A.G.; Congdon, C.C.

    1986-01-01

    This is a report of mammary gland tumors from 62 guinea pigs. The tumors arose in the terminal ductal-lobular units as either lobular acinar carcinoma or cystadenocarcinoma or as papillary carcinomas within large ducts near the mammilla. About half the number of the males had terminal ductal-lobular carcinomas and all but 2 of the papillary duct carcinomas also arose in males. Large tumors frequently exhibited squamous, chondromatous, osseous, fatty and myoepitheliomatous types of tissues. In 2 irradiated males and 1 female the tumors metastasized. Whole-body irradiation did not produce significant changes in the number or sex distribution or in themore » morphology of mammary gland tumors in inbred or outbred guinea pigs. All females had cystic ovaries without increase in granulosa cells, 24 (66.6%) had uterine tumors and 13 (34.2%) had adrenal gland tumors; all males had atrophic testes, 5 (16.5%) had testicular and 6 (22.2%) had adrenal gland tumors.« less

  1. CXCR4 expression in feline mammary carcinoma cells: evidence of a proliferative role for the SDF-1/CXCR4 axis

    PubMed Central

    2012-01-01

    Background Mammary tumours frequently develop in female domestic cats being highly malignant in a large percentage of cases. Chemokines regulate many physiological and pathological processes including organogenesis, chemotaxis of inflammatory cells, as well as tumour progression and metastasization. In particular, the chemokine/receptor pair SDF-1/CXCR4 has been involved in the regulation of metastatic potential of neoplastic cells, including breast cancer. The aim of this study was the immunohistochemical defininition of the expression profile of CXCR4 in primary and metastatic feline mammary carcinomas and the evaluation of the role of SDF-1 in feline mammary tumour cell proliferation. Results A total of 45 mammary surgical samples, including 33 primary tumours (31 carcinomas and 2 adenomas), 6 metastases, and 4 normal mammary tissues were anlyzed. Tumor samples were collected from a total number of 26 animals, as in some cases concurrent occurrence of neoplasm in more than one mammary gland was observed. Tissues were processed for standard histological examination, and all lesions were classified according to the World Health Organization criteria. CXCR4 expression in neoplastic cells was evaluated by immunohistochemistry. The level of CXCR4 immunoreactivity was semi-quantitatively estimated as CXCR4 score evaluating both the number of positive cells and the intensity of staining. Six primary, fibroblast-free primary cultures were obtained from fresh feline mammary carcinomas and characterized by immunofluorescence for CXCR4 and malignant mammary cell marker expression. SDF-1-dependent in vitro proliferative effects were also assayed. CXCR4 expression was observed in 29 out of 31 malignant tissues with a higher CXCR4 score observed in 4 out of 6 metastatic lesions than in the respective primary tumours. In 2 benign lesions analyzed, only the single basaloid adenoma showed a mild positive immunostaining against CXCR4. Normal tissue did not show CXCR4

  2. Effects of xanthosine on gene expression of mammary epithelial cells using RNA sequencing of goat milk fat globules

    USDA-ARS?s Scientific Manuscript database

    Although intramammary xanthosine (XS) treatment was reported to increase the mammary stem cell population and milk yield in bovine and caprine, underlying molecular mechanisms remain unclear. The goal of this study was to evaluate effects of XS treatment on the mammary transcriptome in early lactati...

  3. The calcium-sensing receptor regulates mammary gland parathyroid hormone–related protein production and calcium transport

    PubMed Central

    VanHouten, Joshua; Dann, Pamela; McGeoch, Grace; Brown, Edward M.; Krapcho, Karen; Neville, Margaret; Wysolmerski, John J.

    2004-01-01

    The transfer of calcium from mother to milk during lactation is poorly understood. In this report, we demonstrate that parathyroid hormone–related protein (PTHrP) production and calcium transport in mammary epithelial cells are regulated by extracellular calcium acting through the calcium-sensing receptor (CaR). The CaR becomes expressed on mammary epithelial cells at the transition from pregnancy to lactation. Increasing concentrations of calcium, neomycin, and a calcimimetic compound suppress PTHrP secretion by mammary epithelial cells in vitro, whereas in vivo, systemic hypocalcemia increases PTHrP production, an effect that can be prevented by treatment with a calcimimetic. Hypocalcemia also reduces overall milk production and calcium content, while increasing milk osmolality and protein concentrations. The changes in milk calcium content, milk osmolality, and milk protein concentration were mitigated by calcimimetic infusions. Finally, in a three-dimensional culture system that recapitulates the lactating alveolus, activation of the basolateral CaR increases transcellular calcium transport independent of its effect on PTHrP. We conclude that the lactating mammary gland can sense calcium and adjusts its secretion of calcium, PTHrP, and perhaps water in response to changes in extracellular calcium concentration. We believe this defines a homeostatic system that helps to match milk production to the availability of calcium. PMID:14966569

  4. Chemoprevention of Rat Mammary Carcinogenesis by Apiaceae Spices.

    PubMed

    Aqil, Farrukh; Jeyabalan, Jeyaprakash; Munagala, Radha; Ravoori, Srivani; Vadhanam, Manicka V; Schultz, David J; Gupta, Ramesh C

    2017-02-16

    Scientific evidence suggests that many herbs and spices have medicinal properties that alleviate symptoms or prevent disease. In this study, we examined the chemopreventive effects of the Apiaceae spices, anise, caraway, and celery seeds against 17β-estrogen (E2)-mediated mammary tumorigenesis in an ACI (August-Copenhagen Irish) rat model. Female ACI rats were given either control diet (AIN 93M) or diet supplemented with 7.5% ( w / w ) of anise, caraway, or celery seed powder. Two weeks later, one half of the animals in each group received subcutaneous silastic implants of E2. Diet intake and body weight were recorded weekly, and animals were euthanized after 3 and 12 weeks. E2-treatment showed significantly (2.1- and 3.4-fold) enhanced growth of pituitary gland at 3 and 12 weeks, respectively. All test spices significantly offset the pituitary growth by 12 weeks, except celery which was effective as early as three weeks. Immunohistochemical analysis for proliferative cell nuclear antigen (PCNA) in mammary tissues showed significant reduction in E2-mediated mammary cell proliferation. Test spices reduced the circulating levels of both E2 and prolactin at three weeks. This protection was more pronounced at 12 weeks, with celery eliciting the highest effect. RT-PCR and western blot analysis were performed to determine the potential molecular targets of the spices. Anise and caraway diets significantly offset estrogen-mediated overexpression of both cyclin D1 and estrogen receptor α (ERα). The effect of anise was modest. Likewise, expression of CYP1B1 and CYP1A1 was inhibited by all test spices. Based on short-term molecular markers, caraway was selected over other spices based on its enhanced effect on estrogen-associated pathway. Therefore, a tumor-end point study in ACI rats was conducted with dietary caraway. Tumor palpation from 12 weeks onwards revealed tumor latency of 29 days in caraway-treated animals compared with first tumor appearance at 92 days in

  5. Chemoprevention of Rat Mammary Carcinogenesis by Apiaceae Spices

    PubMed Central

    Aqil, Farrukh; Jeyabalan, Jeyaprakash; Munagala, Radha; Ravoori, Srivani; Vadhanam, Manicka V.; Schultz, David J.; Gupta, Ramesh C.

    2017-01-01

    Scientific evidence suggests that many herbs and spices have medicinal properties that alleviate symptoms or prevent disease. In this study, we examined the chemopreventive effects of the Apiaceae spices, anise, caraway, and celery seeds against 17β-estrogen (E2)-mediated mammary tumorigenesis in an ACI (August-Copenhagen Irish) rat model. Female ACI rats were given either control diet (AIN 93M) or diet supplemented with 7.5% (w/w) of anise, caraway, or celery seed powder. Two weeks later, one half of the animals in each group received subcutaneous silastic implants of E2. Diet intake and body weight were recorded weekly, and animals were euthanized after 3 and 12 weeks. E2-treatment showed significantly (2.1- and 3.4-fold) enhanced growth of pituitary gland at 3 and 12 weeks, respectively. All test spices significantly offset the pituitary growth by 12 weeks, except celery which was effective as early as three weeks. Immunohistochemical analysis for proliferative cell nuclear antigen (PCNA) in mammary tissues showed significant reduction in E2-mediated mammary cell proliferation. Test spices reduced the circulating levels of both E2 and prolactin at three weeks. This protection was more pronounced at 12 weeks, with celery eliciting the highest effect. RT-PCR and western blot analysis were performed to determine the potential molecular targets of the spices. Anise and caraway diets significantly offset estrogen-mediated overexpression of both cyclin D1 and estrogen receptor α (ERα). The effect of anise was modest. Likewise, expression of CYP1B1 and CYP1A1 was inhibited by all test spices. Based on short-term molecular markers, caraway was selected over other spices based on its enhanced effect on estrogen-associated pathway. Therefore, a tumor-end point study in ACI rats was conducted with dietary caraway. Tumor palpation from 12 weeks onwards revealed tumor latency of 29 days in caraway-treated animals compared with first tumor appearance at 92 days in control

  6. Proteomics and pathway analysis of N-glycosylated mammary gland proteins in response to Escherichia coli mastitis in cattle.

    PubMed

    Yang, Yongxin; Shen, Weijun; Zhao, Xiaowei; Zhao, Huiling; Huang, Dongwei; Cheng, Guanglong

    2014-06-01

    The aim of this study was to investigate the N-linked glycosylated protein profile of mammary tissue from healthy cows and cows with mastitis due to Escherichia coli, in order to understand the molecular mechanisms of the host response to mastitis. N-glycopeptides were enriched with a lectin mixture and identified through high-accuracy mass spectrometry. A total of 551 N-glycosylation sites, corresponding to 294 proteins, were identified in the mammary tissues of healthy cows; these glycoproteins were categorised into three functional groups and clustered into 11 specific pathways. A total of 511 N-glycosylation sites, corresponding to 283 glycosylated proteins, were detected in the mammary tissues of cows with E. coli mastitis. There were differences in N-glycosylation sites in 98 proteins in the mammary tissues of healthy cows and cows with mastitis due to E. coli. Most proteins with altered glycosylation were those involved in responses to stress, cell adhesion and the immune response, and were assigned to five specific pathways based on their gene ontology annotation. The results from this study show that the glycosylated protein profile in the mammary tissues of healthy and mastitic cows are different, and altered glycoproteins are associated with several pathways, including the lysosome and O-glycan biosynthesis pathways. Copyright © 2014. Published by Elsevier Ltd.

  7. Ultrasonography and progesterone concentration at a single time point for the detection of puberty in dairy heifers.

    PubMed

    Archbold, H; Buckley, F; Pierce, K M; Begley, N; Mee, J F

    2012-06-01

    Data were available from 1657 heifers across 48 dairy farms which were visited once, on average 9 days (± 5.2) prior to the mating start date (23 April, ± 12.6). Blood samples were collected via coccygeal venepuncture for progesterone (P4) analysis, and animals were scanned for the presence or absence of corpora lutea (CL), to determine the luteal status. A comparison of luteal status between ultrasound (CL identified) and P4 (≥ 1 ng/ml), based on a single measurement point, showed poor agreement (K = 0.32). The majority of animals were classified as luteal (76%) using both ultrasonography and P4. There was excellent agreement between luteal status detected by ultrasonography alone and luteal status assigned by a combination of ultrasonography and P4 (K = 0.93). The agreement between luteal status assigned by P4 and luteal status assigned by the combination of ultrasonography and P4 was poor (K = 0.37). These results indicate that at a single examination, ultrasonography is the preferred modality to determine the luteal status of maiden heifers. © 2011 Blackwell Verlag GmbH.

  8. Ocular melanoma and mammary mucinous carcinoma in an African lion.

    PubMed

    Cagnini, Didier Q; Salgado, Breno S; Linardi, Juliana L; Grandi, Fabrizio; Rocha, Rafael M; Rocha, Noeme S; Teixeira, Carlos R; Del Piero, Fabio; Sequeira, Julio L

    2012-09-25

    Reports of neoplasms in Panthera species are increasing, but they are still an uncommon cause of disease and death in captive wild felids. The presence of two or more primary tumor in large felids is rarely reported, and there are no documented cases of ocular melanoma and mammary mucinous carcinoma in African lions. An ocular melanoma and a mammary mucinous carcinoma are described in an African lion (Panthera leo). The first tumour was histologically characterized by the presence of epithelioid and fusiform melanocytes, while the latter was composed of mucus-producing cells with an epithelial phenotype that contained periodic acid-Schiff (PAS) and Alcian blue staining mucins. Metastases of both tumor were identified in various organs and indirect immunohistochemistry was used to characterize them. Peribiliary cysts were observed in the liver. This is the first description of these tumor in African lions.

  9. Bone morphogenetic protein-4 strongly potentiates growth factor-induced proliferation of mammary epithelial cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Montesano, Roberto; Sarkoezi, Rita; Schramek, Herbert

    2008-09-12

    Bone morphogenetic proteins (BMPs) are multifunctional cytokines that elicit pleiotropic effects on biological processes such as cell proliferation, cell differentiation and tissue morphogenesis. With respect to cell proliferation, BMPs can exert either mitogenic or anti-mitogenic activities, depending on the target cells and their context. Here, we report that in low-density cultures of immortalized mammary epithelial cells, BMP-4 did not stimulate cell proliferation by itself. However, when added in combination with suboptimal concentrations of fibroblast growth factor (FGF)-2, FGF-7, FGF-10, epidermal growth factor (EGF) or hepatocyte growth factor (HGF), BMP-4 potently enhanced growth factor-induced cell proliferation. These results reveal a hithertomore » unsuspected interplay between BMP-4 and growth factors in the regulation of mammary epithelial cell proliferation. We suggest that the ability of BMP-4 to potentiate the mitogenic activity of multiple growth factors may contribute to mammary gland ductal morphogenesis as well as to breast cancer progression.« less

  10. Luminal epithelial cells within the mammary gland can produce basal cells upon oncogenic stress.

    PubMed

    Hein, S M; Haricharan, S; Johnston, A N; Toneff, M J; Reddy, J P; Dong, J; Bu, W; Li, Y

    2016-03-17

    In the normal mammary gland, the basal epithelium is known to be bipotent and can generate either basal or luminal cells, whereas the luminal epithelium has not been demonstrated to contribute to the basal compartment in an intact and normally developed mammary gland. It is not clear whether cellular heterogeneity within a breast tumor results from transformation of bipotent basal cells or from transformation and subsequent basal conversion of the more differentiated luminal cells. Here we used a retroviral vector to express an oncogene specifically in a small number of the mammary luminal epithelial cells and tested their potential to produce basal cells during tumorigenesis. This in-vivo lineage-tracing work demonstrates that luminal cells are capable of producing basal cells on activation of either polyoma middle T antigen or ErbB2 signaling. These findings reveal the plasticity of the luminal compartment during tumorigenesis and provide an explanation for cellular heterogeneity within a cancer.

  11. Luminal Epithelial Cells within the Mammary Gland Can Produce Basal Cells upon Oncogenic Stress

    PubMed Central

    Hein, Sarah M.; Haricharan, Svasti; Johnston, Alyssa N.; Toneff, Michael J.; Reddy, Jay P.; Dong, Jie; Bu, Wen; Li, Yi

    2015-01-01

    In the normal mammary gland, the basal epithelium is known to be bi-potent and can generate either basal or luminal cells, whereas the luminal epithelium has not been demonstrated to contribute to the basal compartment in an intact and normally developed mammary gland. It is not clear whether cellular heterogeneity within a breast tumor results from transformation of bi-potent basal cells or from transformation and subsequent basal conversion of the more differentiated luminal cells. Here, we used a retroviral vector to express an oncogene specifically in a small number of the mammary luminal epithelial cells and tested their potential to produce basal cells during tumorigenesis. This in vivo lineage tracing work demonstrates that luminal cells are capable of producing basal cells upon activation of either Polyoma Middle T antigen (PyMT) or ErbB2 signaling. These findings reveal the plasticity of the luminal compartment during tumorigenesis and provide an explanation for cellular heterogeneity within a cancer. PMID:26096929

  12. An unanticipated diagnosis with bedside ultrasonography in patients with acute abdominal pain: rectus hematoma

    PubMed Central

    Ünlüer, Erden Erol; Kaykısız, Eylem Kuday

    2017-01-01

    Although abdominal pain is a common presentation in emergency departments, rectus sheath hematoma (RSH) is among the rarest diagnosis. Here we present 2 cases of RSH likely caused by coughing due to upper respiratory tract infection. The two described cases were diagnosed by bedside ultrasonography and confirmed as RSH by computed tomography. Review of patient history and use of ultrasonography are important to avoid misdiagnosisof RSH. PMID:28748020

  13. Periareolar techniques for mammary reduction and elevation.

    PubMed

    de Benito, J; Sanza, I F

    1993-01-01

    Between June 1990 and June 1992 we carried out 56 breast operations: 18 reductions, 32 mastopexies, and 6 implant changes. The surgical techniques used in all cases basically consisted of three phases: the periareolar incision, the creation of the superior pedicle with two medial and lateral flaps, and the "anchoring," crossed by both flaps in order to hold up the mammary gland. The diameter of the "doughnut" of skin that we had to deepidermize varied between 5 and 15 cm, thus raising the nipple-areola complex by as much as 10 cm. The volume of tissue removed from the hypertrophic breast ranged from 70 to 520 g. In 24 of the 32 mastopexies, the use of a silicone implant was necessary in order to provide greater volume, texture, and better mammary contour. In these cases the size of the prostheses varied between 120 and 300 cc. All patients completed the postop followup in the normal way. Only three patients suffered a slight dehiscence of the periareolar suture, which was solved within a few days of the operation by means of a Friedreich. The periareolar cutaneous pleats and the hardness of the breast gradually disappeared, as predicted, within a period of 3-4 months; afterward the breast looked perfectly natural.

  14. Casein gene expression in mouse mammary epithelial cell lines: Dependence upon extracellular matrix and cell type

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Medina, D.; Oborn, C.J.; Li, M.L.

    1987-09-01

    The COMMA-D mammary cell line exhibits mammary-specific functional differentiation under appropriate conditions in cell culture. The cytologically heterogeneous COMMA-D parental line and the clonal lines DB-1, TA-5, and FA-1 derived from the COMMA-D parent were examined for similar properties of functional differentiation. In monolayer cell culture, the cell lines DB-1, TA-5, FA-1, and MA-4 were examined for expression of mammary-specific and epithelial-specific proteins by an indirect immunofluorescence assay. The clonal cell lines were relatively homogeneous in their respective staining properties and seemed to represent three subpopulations found in the heterogeneous parental COMMA-D lines. None of the four clonal lines appearedmore » to represent myoepithelial cells. The cell lines were examined for expression of {beta}-casein mRNA in the presence or absence of prolactin. The inducibility of {beta}-casein in the COMMA-D cell line was further enhanced by a reconstituted basement membrane preparation enriched in laminin, collagen IV, and proteoglycans. These results support the hypothesis that the functional response of inducible mammary cell populations is a result of interaction among hormones, multiple extracellular matrix components, and specific cell types.« less

  15. Relative quantification of beta-casein expression in primary goat mammary epithelial cell lines.

    PubMed

    Ogorevc, J; Dovč, P

    2015-04-15

    Primary mammary epithelial cell cultures were established from mammary tissue of lactating and non-lactating goats to assess the expression of beta-casein (CSN2) in vitro. Primary cell cultures were established by enzymatic digestion of mammary tissue and characterized using antibodies against cytokeratin 14, cytokeratin 18, and vimentin. The established primary cell lines in the second passage were grown in basal medium on plastic and in hormone-supplemented (lactogenic) medium on plastic and on an extracellular matrix-covered surface, respectively. CSN2 gene expression was evaluated using quantitative reverse transcription PCR. The presence of CSN2 transcripts was detected in all samples, including cells originating from non-lactating goat, grown in basal medium. The presence of CSN2 protein was confirmed using immunofluorescence. Response to the hormonal treatment and cell morphology differed between the cell lines and treatments. In 2 cell lines supplemented with lactogenic hormones in the medium, CSN2 expression was increased, while CSN2 levels in one of the cell lines remained constant, regardless of the treatment. Addition of extracellular matrix showed positive effects on CSN2 transcription activity in 1 of the cell lines, while in the other 2 showed no statistically significant effects. CSN2 expression appeared to depend on subtle differences in physiological state of the starting tissue material, growth conditions, cell types present in the culture, and methods used for cell culture establishment. Further studies are necessary to identify factors that determine hormone-responsiveness and transcriptional activity of milk protein genes in goat primary mammary cell cultures.

  16. Can contrast-enhanced ultrasonography improve Zone III REBOA placement for prehospital care?

    PubMed

    Chaudery, Muzzafer; Clark, James; Morrison, Jonathan J; Wilson, Mark H; Bew, Duncan; Darzi, Ara

    2016-01-01

    Torso hemorrhage is the primary cause of potentially preventable mortality in trauma. Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been advocated as an adjunct to bridge patients to definitive hemorrhage control. The primary aim of this study was to assess whether contrast-enhanced ultrasonography can improve the accuracy of REBOA placement in the infrarenal aorta (Zone III). A fluoroscopy-free "enhanced" Zone III REBOA technique was developed using a porcine cadaver model. A "standard" over-the-wire Seldinger technique was used, which was enhanced with the addition of a microbubble contrast medium to inflate the balloon, observed with ultrasonography. Following this, attending- and resident-level physicians were randomized into two groups. They were taught either the enhanced with ultrasonography guidance (Group A) or the standard measuring length of catheter insertion (Group B) technique as part of a human cadaver trauma skills course. Outcomes assessed included time (seconds) from insertion to inflation, accuracy, and missed targets. All results were benchmarked against three endovascular experts. There were 20 participants who performed REBOA with Group A (51 [31]) being significantly faster than Group B (90 [63]) (p = 0.003) and more accurate (p = 0.023) with no missed targets. Group B had five missed targets, the most common error being inflation within Zone II. For Zone III REBOA, contrast-enhanced ultrasonography technique is faster and more accurate than the standard technique. This may have value in time-critical and austere environments. Clinical studies are now required to evaluate this approach further.

  17. A cyclized peptide derived from alpha fetoprotein inhibits the proliferation of ER-positive canine mammary cancer cells.

    PubMed

    Torres, Cristian Gabriel; Pino, Ana María; Sierralta, Walter Daniel

    2009-06-01

    The effects of estradiol (E2) and of an AFP-derived cyclized peptide (cP) on the proliferation of primary cultures of cancer cells isolated from spontaneous canine mammary tumors were studied. The cellular response to E2 and cP was related to the expression of estradiol receptor (isoforms alpha and beta). In ER-positive cells, 2 nM estradiol increased cell proliferation and the phosphorylation of ERK1/2; 2 microg/ml cP inhibited all these effects. Estradiol also increased HER2 immunoreactivity in ER-positive cells, an effect that was reverted to its basal values by cP. Estradiol stimulated in these cells the release of MMP2 and MMP9 and the shedding of HB-EGF, effects that the cP did not affect. ER-negative cells were refractory to estradiol or cP. All canine mammary tumor cells in culture responded to treatments analogously to human mammary cancer cells. Our results support the proposal of cP as a new, potentially effective therapeutic agent for the management of mammary cancer.

  18. Expansion of stem cells counteracts age-related mammary regression in compound Timp1/Timp3 null mice.

    PubMed

    Jackson, Hartland W; Waterhouse, Paul; Sinha, Ankit; Kislinger, Thomas; Berman, Hal K; Khokha, Rama

    2015-03-01

    Age is the primary risk factor for breast cancer in women. Bipotent basal stem cells actively maintain the adult mammary ductal tree, but with age tissues atrophy. We show that cell-extrinsic factors maintain the adult stem cell pool during ageing and dictate tissue stoichiometry. Mammary stem cells spontaneously expand more than 11-fold in virgin adult female mice lacking specific genes for TIMPs, the natural metalloproteinase inhibitors. Compound Timp1/Timp3 null glands exhibit Notch activation and accelerated gestational differentiation. Proteomics of mutant basal cells uncover altered cytoskeletal and extracellular protein repertoires, and we identify aberrant mitotic spindle orientation in these glands, a process that instructs asymmetric cell division and fate. We find that progenitor activity normally declines with age, but enriched stem/progenitor pools prevent tissue regression in Timp mutant mammary glands without affecting carcinogen-induced cancer susceptibility. Thus, improved stem cell content can extend mouse mammary tissue lifespan without altering cancer risk in this mouse model.

  19. High-resolution ultrasonography in assessment of nail-related disorders.

    PubMed

    Singh, R; Bryson, D; Singh, H P; Jeyapalan, K; Dias, J J

    2012-09-01

    Disorders of the nail can pose a diagnostic challenge, and non-invasive imaging is frequently required to clarify diagnosis and delineate anatomy pre-operatively. We explored the use of high-resolution ultrasonography in the assessment of patients with nail disorders attending orthopaedic hand clinics. A search of a university teaching hospital musculoskeletal radiology database identified 36 patients (mean age 54.2 years) where ultrasonography was used to assess nail-related disorders between April 2003 and January 2007. Clinical, surgical and histological findings were correlated in these cases with ultrasound reports. Ultrasound findings correlated with the provisional diagnosis in 20 (61%) of 33 patients and provided a diagnosis in 3 patients where a provisional diagnosis was unavailable. In 7 of the 13 cases where the clinical diagnosis differed from ultrasound findings, a lump originally diagnosed as cystic in origin was shown to be solid on ultrasound. Different nail pathologies showed different characteristics on ultrasonography, including differences in vascularity, echogenicity, changes in nail structure/shape and extension into the nail bed, matrix, fold or evidence of bony erosion. The ultrasound findings correlated with histological analysis and intra-operative assessment in 10 of 15 patients who underwent operative treatment. Ultrasound provides important information on the anatomy of the nail apparatus and can differentiate solid and cystic lesions. It can be used as a diagnostic tool and can therefore help in pre-operative planning of nail-related disorders. In our series ultrasound supported or improved upon the clinical diagnosis in 31 (86%) out of the 36 patients presenting with nail-related disorders.

  20. Spontaneous feline mammary intraepithelial lesions as a model for human estrogen receptor- and progesterone receptor-negative breast lesions

    PubMed Central

    2010-01-01

    Background Breast cancer is the most frequently diagnosed cancer in women. Intraepithelial lesions (IELs), such as usual ductal hyperplasia (UH), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) are risk factors that predict a woman's chance of developing invasive breast cancer. Therefore, a comparative study that establishes an animal model of pre-invasive lesions is needed for the development of preventative measures and effective treatment for both mammary IELs and tumors. The purpose of this study was to characterize the histologic and molecular features of feline mammary IELs and compare them with those in women. Methods Formalin-fixed, paraffin-embedded specimens (n = 205) from 203 female cats with clinical mammary disease were retrieved from the archives of the Purdue University Animal Disease Diagnostic Laboratory and Veterinary Teaching Hospital (West Lafayette, IN), and the Department of Pathology and Veterinary Clinic, School of Veterinary Medicine (Sassari, Italy). Histologic sections, stained with hematoxylin and eosin (HE), were evaluated for the presence of IELs in tissue adjacent to excised mammary tumors. Lesions were compared to those of humans. Immunohistochemistry for estrogen receptor (ER-alpha), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2/neu) and Ki-67 was performed in IELs and adjacent tumor tissues. Results Intraepithelial lesions were found in 57 of 203 (28%) feline mammary specimens and were categorized as UH (27%), ADH (29%), and DCIS (44%). Most IELs with atypia (ADH and DCIS) were associated with mammary cancer (91%), whereas UH was associated with benign lesions in 53% of cases. Feline IELs were remarkably similar to human IELs. No ER or PR immunoreactivity was detected in intermediate-grade or high-grade DCIS or their associated malignant tumors. HER-2 protein overexpression was found in 27% of IELs. Conclusion The remarkable similarity of feline mammary IELs to those of humans

  1. Diagnostic PET Imaging of Mammary Microcalcifications Using 64Cu-DOTA-Alendronate in a Rat Model of Breast Cancer.

    PubMed

    Ahrens, Bradley J; Li, Lin; Ciminera, Alexandra K; Chea, Junie; Poku, Erasmus; Bading, James R; Weist, Michael R; Miller, Marcia M; Colcher, David M; Shively, John E

    2017-09-01

    The development of improved breast cancer screening methods is hindered by a lack of cancer-specific imaging agents and effective small-animal models to test them. The purpose of this study was to evaluate 64 Cu-DOTA-alendronate as a mammary microcalcification-targeting PET imaging agent, using an ideal rat model. Our long-term goal is to develop 64 Cu-DOTA-alendronate for the detection and noninvasive differentiation of malignant versus benign breast tumors with PET. Methods: DOTA-alendronate was synthesized, radiolabeled with 64 Cu, and administered to normal or tumor-bearing aged, female, retired breeder Sprague-Dawley rats for PET imaging. Mammary tissues were subsequently labeled and imaged with light, confocal, and electron microscopy to verify microcalcification targeting specificity of DOTA-alendronate and elucidate the histologic and ultrastructural characteristics of the microcalcifications in different mammary tumor types. Tumor uptake, biodistribution, and dosimetry studies were performed to evaluate the efficacy and safety of 64 Cu-DOTA-alendronate. Results: 64 Cu-DOTA-alendronate was radiolabeled with a 98% yield. PET imaging using aged, female, retired breeder rats showed specific binding of 64 Cu-DOTA-alendronate in mammary glands and mammary tumors. The highest uptake of 64 Cu-DOTA-alendronate was in malignant tumors and the lowest uptake in benign tumors and normal mammary tissue. Confocal analysis with carboxyfluorescein-alendronate confirmed the microcalcification binding specificity of alendronate derivatives. Biodistribution studies revealed tissue alendronate concentrations peaking within the first hour, then decreasing over the next 48 h. Our dosimetric analysis demonstrated a 64 Cu effective dose within the acceptable range for clinical PET imaging agents and the potential for translation into human patients. Conclusion: 64 Cu-DOTA-alendronate is a promising PET imaging agent for the sensitive and specific detection of mammary tumors as

  2. Survival of mouse mammary gland transplants of normal, hyperplastic, and tumor tissues exposed to X-rays

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Faulkin, L.J.; Mitchell, D.J.; Cardiff, R.D.

    1982-04-01

    Mouse mammary tissues, including ducts, prelactating lobules, hyperplastic outgrowth lines, and tumors, were exposed to varying doses of X-rays and then transplanted to fat pads of nonirradiated BALB/c mice for study. Estimates of the dose of radiation that would allow survival of 50% of the transplants (SD50) were made with the use of probit analysis. Nearly all duct and lobule transplants survived doses of X-rays from 0 to 800 rad. The survival rate declined rapidly following doses above 800 rad, and the calculated SD50 was 1,020 and 1,260 rad for mammary ducts and lobules, respectively. The three hyperplastic outgrowth linesmore » tested gave very different results. Hyperplastic line Z5C1 transplants had better than 90% survival at doses up to 1,200 rad and an SD50 between 1,200 and 1,600 rad. Hyperplastic line Z5D transplants had an SD50 of between 800 and 1,200 rad. Hyperplastic line D1 transplants had a better than 90% survival following doses of 0-600 rad and an SD50 between 600 and 800 rad. The survival of tumor transplants was 100% following doses of X-rays up to 1,200 rad; the SD50 was in excess of 1,600 rad. The mouse mammary transplantation system can be used to study the direct effect of X-rays on normal, premalignant, and malignant mammary tissues and provides a basis for the study of the radiobiology of mammary tissues.« less

  3. Mechanisms Underlying the Very High Susceptibility of the Immature Mammary Gland to Carcinogenic Initiation

    DTIC Science & Technology

    1999-07-01

    the in vivo cytotoxicity of 3 versus 8 week old F344 mammary gland following exposure to either NMU or DMBA using a mammary cell transplantation assay...Epithelial Cell Mutant Frequencies 30E6 with Expression Period following NMU Treatment in vivo 250E-6 ]5WeExrsinPio S200E-6 S150E-6 !! i 50E-6... Dosimetry : Anesthetized rats were irradiated with 6 Mev electrons from a Clinac 2300 medical linear accelerator. The rats were laid supine on the

  4. Hormonally active doses of isoflavone aglycones promote mammary and endometrial carcinogenesis and alter the molecular tumor environment in Donryu rats.

    PubMed

    Kakehashi, Anna; Tago, Yoshiyuki; Yoshida, Midori; Sokuza, Yui; Wei, Min; Fukushima, Shoji; Wanibuchi, Hideki

    2012-03-01

    Our research is focused on modifying effects of an isoflavone aglycones (IAs)-rich extract at a hormonally active dose of 150 mg/kg body weight/day on mammary and endometrial carcinogenesis in female Donryu rats. IA administered for 2 weeks in a phytoestrogen-low diet exerted estrogenic activity and induced cell proliferation in the uterus of ovariectomized rats. Furthermore, administration for 4 weeks resulted in elevation of cell proliferation in the mammary glands of 7,12-dimethylbenz[a]anthracene (DMBA)-treated animals. Forty weeks of postpubertal administration of IA to 5-week-old rats after initiation of mammary and endometrial carcinogenesis with DMBA and N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) caused significant increase of incidence and multiplicity of mammary adenocarcinoma, multiplicities of endometrial atypical hyperplasia, adenomatous polyps, and an increased trend of uterine adenocarcinomas. Liquid chromatography with tandem mass spectrometry and immunohistochemical analyses revealed significant elevation of tumorigenesis-related proteins such as S100 calcium-binding protein A8, kininogen 1, and annexins 1 and 2 in mammary adenocarcinomas and cadherin EGF LAG seven-pass G-type receptor 2, DEAD box polypeptide 1, and cysteine- and glycine-rich protein 1 in uterine proliferative lesions of IA-treated animals. Those changes are likely to be related to modulation of estrogen receptor (ER), AP1, nuclear factor-kappa B, and actin signaling pathways. Our results indicate that the postpubertal exposure of Donryu rats to IA at an estrogenic dose results in promotion of mammary and uterine carcinogenesis induced by DMBA and ENNG, which might be related to the activation of ER-dependent signaling and alteration of the molecular tumor environment in the mammary gland and endometrium.

  5. MRI versus ultrasonography to assess meniscal abnormalities in acute knees.

    PubMed

    Cook, James L; Cook, Cristi R; Stannard, James P; Vaughn, Gavin; Wilson, Nichole; Roller, Brandon L; Stoker, Aaron M; Jayabalan, Prakash; Hdeib, Moses; Kuroki, Keiichi

    2014-08-01

    While magnetic resonance imaging (MRI) is often considered the "gold standard" diagnostic imaging modality for detection of meniscal abnormalities, it is associated with misdiagnosis in as high as 47% of cases, is costly, and is not readily available to a large number of patients. Ultrasonographic examination of the knee has been reported to be an effective diagnostic tool for this purpose with the potential to overcome many of the shortcomings of MRI. The purpose of this study is to determine the clinical usefulness of ultrasonography for diagnosis of meniscal pathology in patients with acute knee pain and compare its diagnostic accuracy to MRI in a clinical setting. With Institutional Review Board approval, patients (n = 71) with acute knee pain were prospectively enrolled with informed consent. Preoperative MRI (1.5 T) was performed on each affected knee using the hospital's standard equipment and protocols and read by faculty radiologists trained in musculoskeletal MRI. Ultrasonographic assessments of each affected knee were performed by one of two faculty members trained in musculoskeletal ultrasonography using a 10 to 14 MHz linear transducer. Arthroscopic evaluation of affected knees was performed by one of three faculty orthopedic surgeons to assess and record all joint pathology, which served as the reference standard for determining presence, type, and severity of meniscal pathology. All evaluators for each diagnostic modality were blinded to all other data. Data were collected and compared by a separate investigator to determine sensitivity (Sn), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), correct classification rate (CCR), likelihood ratios (LR[+] and LR[-]), and odds ratios. Preoperative ultrasonographic assessment of meniscal pathology was associated with Sn = 91.2%, Sp = 84.2%, PPV = 94.5%, NPV = 76.2%, CCR = 89.5%, LR(+) = 5.78, and LR(-) = 0.10. Preoperative MRI assessment of

  6. Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses

    PubMed Central

    Huang, Stephen S. H.; Almansa, Raquel; Leon, Alberto; Xu, Luoling; Bartoszko, Jessica; Kelvin, David J.; Kelvin, Alyson A.

    2015-01-01

    Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus

  7. Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses.

    PubMed

    Paquette, Stéphane G; Banner, David; Huang, Stephen S H; Almansa, Raquel; Leon, Alberto; Xu, Luoling; Bartoszko, Jessica; Kelvin, David J; Kelvin, Alyson A

    2015-10-01

    Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus

  8. Cathelicidin production and release by mammary epithelial cells during infectious mastitis.

    PubMed

    Cubeddu, Tiziana; Cacciotto, Carla; Pisanu, Salvatore; Tedde, Vittorio; Alberti, Alberto; Pittau, Marco; Dore, Simone; Cannas, Agnese; Uzzau, Sergio; Rocca, Stefano; Addis, Maria Filippa

    2017-07-01

    Cathelicidins are well-characterized antimicrobial peptides (AMPs) that are present in significant amounts in mastitic milk. Neutrophils are believed to be the main producers of these AMPs, while the role of mammary epithelial cells (MECs) in their production and release is still unclear. In this work, cathelicidin production patterns were investigated in mammary tissues of ewes infected by Staphylococcus aureus, Streptococcus uberis, or Mycoplasma agalactiae, with a combined approach including immunohistochemistry, immune-colocalization, and fluorescent in situ hybridization. Our results confirm that MECs produce and release cathelicidins in response to different mastitis pathogens. As opposed to neutrophils, however, MECs do not seem to store the preformed protein precursor in their cytoplasm, but appear to synthesize and release it only upon exposure to the microorganisms. Cathelicidin production by MECs appears to occur before leukocyte influx in the milk, suggesting a role for these cells in the initial response of the mammary epithelium to microbial infection. Once in the milk, infiltrating neutrophils release massive amounts of cathelicidin by degranulation and production of neutrophil extracellular traps, acting as the main contributor for cathelicidin abundance in mastitic milk. Taken together, our results support the active contribution of MECs to cathelicidin production and release, and reinforce the value of cathelicidins as sensitive and pathogen-independent mastitis markers. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Comparison of ultrasonography and physical examination in the diagnosis of incisional hernia in a prospective study.

    PubMed

    Bloemen, A; van Dooren, P; Huizinga, B F; Hoofwijk, A G M

    2012-02-01

    Incisional hernia is a frequent complication of abdominal surgery (incidence 2-20%). Diagnosis by physical examination is sometimes difficult, especially in small incisional hernias or in obese patients. The additional diagnostic value of standardized ultrasonography was evaluated in this prospective study. A total of 456 patients participating in a randomized trial comparing two suture materials for closure of the abdominal fascia underwent physical examination and ultrasonography at 6-month intervals. Wound complaints and treatment of incisional hernia were also noted. Statistical analysis was performed using the Chi-squared and Fisher's exact tests (SPSS). Interest variability analysis was performed. During a median follow-up of 31 months, 103 incisional hernias were found. A total of 82 incisional hernias were found by physical examination and an additional 21 with ultrasonography. Six of these additional hernias were symptomatic and only one of the additional hernias received operative treatment. The false-negative rates for physical examination and ultrasonography were 25.3 and 24.4%, respectively. Interest variability was low, with a Kappa of 0.697 (P < 0.001). There are no clear diagnostic criteria for incisional hernia available in the literature. Standardized combination of ultrasonography with physical examination during follow-up yields a significant number of, mostly asymptomatic, hernias, which would not be found using physical examination alone. This is especially relevant in research settings.

  10. In-utero diagnosis of Norrie disease by ultrasonography.

    PubMed

    Redmond, R M; Vaughan, J I; Jay, M; Jay, B

    1993-03-01

    Obstetric ultrasonography of an obligate Norrie disease carrier revealed bilateral retinal detachments in a third trimester male fetus. Postnatal examination confirmed the diagnosis of Norrie disease. DNA linkage analysis with the markers L1.28 and MAO had been uninformative for this family. This report suggests that retinal detachment occurs late in the gestation of the affected fetus.

  11. Deletion of IL-33R attenuates VEGF expression and enhances necrosis in mammary carcinoma

    PubMed Central

    Pejnovic, Nada N.; Mitrovic, Slobodanka L. J.; Arsenijevic, Nebojsa N.; Simovic Markovic, Bojana J.; Lukic, Miodrag L.

    2016-01-01

    Interleukin-33 (IL-33)/IL-33 receptor (IL-33R, ST2) signaling pathway promotes mammary cancer growth and metastasis by inhibiting anti-tumor immunity. However, the role of IL-33/IL-33R axis in neoangiogenesis and tumor necrosis is not elucidated. Therefore, the aim of this study was to investigate the role of IL-33/IL-33R axis in mammary tumor necrosis. Deletion of IL-33R (ST2) gene in BALB/c mice enhanced tumor necrosis and attenuated tumor growth in 4T1 breast cancer model, which was associated with markedly decreased expression of vascular endothelial growth factor (VEGF) and IL-33 in mammary tumor cells. We next analyzed IL-33, IL-33R and VEGF expression and microvascular density (MVD) in breast tumors from 40 female patients with absent or present tumor necrosis. We found significantly higher expression of IL-33, IL-33R and VEGF in breast cancer tissues with absent tumor necrosis. Both, IL-33 and IL-33R expression correlated with VEGF expression in tumor cells. Further, VEGF expression positively correlated with MVD in perinecrotic zone. Taking together, our data indicate that IL-33/IL-33R pathway is critically involved in mammary tumor growth by facilitating expression of pro-angiogenic VEGF in tumor cells and attenuating tumor necrosis. These data add an unidentified mechanism by which IL-33/IL-33R axis facilitates tumor growth. PMID:26919112

  12. Deletion of IL-33R attenuates VEGF expression and enhances necrosis in mammary carcinoma.

    PubMed

    Milosavljevic, Milos Z; Jovanovic, Ivan P; Pejnovic, Nada N; Mitrovic, Slobodanka L J; Arsenijevic, Nebojsa N; Simovic Markovic, Bojana J; Lukic, Miodrag L

    2016-04-05

    Interleukin-33 (IL-33)/IL-33 receptor (IL-33R, ST2) signaling pathway promotes mammary cancer growth and metastasis by inhibiting anti-tumor immunity. However, the role of IL-33/IL-33R axis in neoangiogenesis and tumor necrosis is not elucidated. Therefore, the aim of this study was to investigate the role of IL-33/IL-33R axis in mammary tumor necrosis. Deletion of IL-33R (ST2) gene in BALB/c mice enhanced tumor necrosis and attenuated tumor growth in 4T1 breast cancer model, which was associated with markedly decreased expression of vascular endothelial growth factor (VEGF) and IL-33 in mammary tumor cells. We next analyzed IL-33, IL-33R and VEGF expression and microvascular density (MVD) in breast tumors from 40 female patients with absent or present tumor necrosis. We found significantly higher expression of IL-33, IL-33R and VEGF in breast cancer tissues with absent tumor necrosis. Both, IL-33 and IL-33R expression correlated with VEGF expression in tumor cells. Further, VEGF expression positively correlated with MVD in perinecrotic zone. Taking together, our data indicate that IL-33/IL-33R pathway is critically involved in mammary tumor growth by facilitating expression of pro-angiogenic VEGF in tumor cells and attenuating tumor necrosis. These data add an unidentified mechanism by which IL-33/IL-33R axis facilitates tumor growth.

  13. Identification of an immune modulation locus utilising a bovine mammary gland infection challenge model.

    PubMed

    Littlejohn, Mathew D; Turner, Sally-Anne; Walker, Caroline G; Berry, Sarah D; Tiplady, Kathryn; Sherlock, Ric G; Sutherland, Greg; Swift, Simon; Garrick, Dorian; Lacy-Hulbert, S Jane; McDougall, Scott; Spelman, Richard J; Snell, Russell G; Hillerton, J Eric

    2018-05-01

    Inflammation of the mammary gland following bacterial infection, commonly known as mastitis, affects all mammalian species. Although the aetiology and epidemiology of mastitis in the dairy cow are well described, the genetic factors mediating resistance to mammary gland infection are not well known, due in part to the difficulty in obtaining robust phenotypic information from sufficiently large numbers of individuals. To address this problem, an experimental mammary gland infection experiment was undertaken, using a Friesian-Jersey cross breed F2 herd. A total of 604 animals received an intramammary infusion of Streptococcus uberis in one gland, and the clinical response over 13 milkings was used for linkage mapping and genome-wide association analysis. A quantitative trait locus (QTL) was detected on bovine chromosome 11 for clinical mastitis status using micro-satellite and Affymetrix 10 K SNP markers, and then exome and genome sequence data used from the six F1 sires of the experimental animals to examine this region in more detail. A total of 485 sequence variants were typed in the QTL interval, and association mapping using these and an additional 37 986 genome-wide markers from the Illumina SNP50 bovine SNP panel revealed association with markers encompassing the interleukin-1 gene cluster locus. This study highlights a region on bovine chromosome 11, consistent with earlier studies, as conferring resistance to experimentally induced mammary gland infection, and newly prioritises the IL1 gene cluster for further analysis in genetic resistance to mastitis.

  14. PKCθ promotes c-Rel–driven mammary tumorigenesis in mice and humans by repressing estrogen receptor α synthesis

    PubMed Central

    Belguise, Karine; Sonenshein, Gail E.

    2007-01-01

    The vast majority of primary human breast cancer tissues display aberrant nuclear NF-κB c-Rel expression. A causal role for c-Rel in mammary tumorigenesis has been demonstrated using a c-Rel transgenic mouse model; however, tumors developed with a long latency, suggesting a second event is needed to trigger tumorigenesis. Here we show that c-Rel activity in the mammary gland is repressed by estrogen receptor α (ERα) signaling, and we identify an epigenetic mechanism in breast cancer mediated by activation of what we believe is a novel PKCθ-Akt pathway that leads to downregulation of ERα synthesis and derepression of c-Rel. ERα levels were lower in c-Rel–induced mammary tumors compared with normal mammary gland tissue. PKCθ induced c-Rel activity and target gene expression and promoted growth of c-Rel- and c-RelxCK2α–driven mouse mammary tumor–derived cell lines. RNA expression levels of PKCθ and c-Rel target genes were inversely correlated with ERα levels in human breast cancer specimens. PKCθ activated Akt, thereby inactivating forkhead box O protein 3a (FOXO3a) and leading to decreased synthesis of its target genes, ERα and p27Kip1. Thus we have shown that activation of PKCθ inhibits the FOXO3a/ERα/p27Kip1 axis that normally maintains an epithelial cell phenotype and induces c-Rel target genes, thereby promoting proliferation, survival, and more invasive breast cancer. PMID:18037997

  15. Proliferation of Estrogen Receptor alpha Positive Mammary Epithelial Cells is Restrained by TGFbeta1 in Adult Mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ewan, Kenneth B.R.; Oketch-Rabah, Hellen A.; Ravani, Shraddha A.

    2005-03-03

    Transforming growth factor {beta}1 (TGF{beta}1) is a potent inhibitor of mammary epithelial proliferation. In human breast, estrogen receptor {alpha} (ER{alpha}) cells rarely co-localize with markers of proliferation, but their increased frequency correlates with breast cancer risk. To determine whether TGF{beta}1 is necessary for the quiescence of ER{alpha}-positive population, we examined mouse mammary epithelial gland at estrus. Approximately 35% of cells showed TGF{beta}1 activation, which co-localized with nuclear receptor-phosphorylated Smad 2/3, indicating that TGF{beta} signaling is autocrine. Furthermore, nuclear Smad co-localized with nuclear ER{alpha}. To test whether TGF{beta} was functional, we examined genetically engineered mice with different levels of TGF{beta}1. ER{alpha}more » co-localization with markers of proliferation (i.e. Ki-67 or BrdU) at estrus was significantly increased in the mammary glands of Tgf{beta}1 C57/bl/129SV heterozygote mice. This relationship was maintained following pregnancy, but was absent at puberty. Conversely, mammary epithelial expression of constitutively active TGF{beta}1 via the MMTV promoter suppressed proliferation of ER{alpha} positive cells. Thus, TGF{beta}1 activation functionally restrains ER{alpha} positive cells from proliferating in adult mammary gland. Accordingly, we propose that TGF{beta}1 dysregulation may promote proliferation of ER{alpha} positive cells associated with breast cancer risk in humans.« less

  16. Antiproliferative Effects of Oxytocin and Desmopressin on Canine Mammary Cancer Cells

    PubMed Central

    Benavente, Micaela Andrea; Bianchi, Carolina Paula; Imperiale, Fernanda; Aba, Marcelo Alfredo

    2016-01-01

    Neoplasms of the mammary gland represent the most frequent tumor type in the female dog, and according to the histologic criteria, approximately 50% of them are malignant. In the most aggressive cases of mammary cancer, surgery is not enough to warrant a favorable outcome, and adjuvant therapies are needed to improve the patient’s overall survival. The aim of the present study was to evaluate the effects of two peptides on proliferation of a canine mammary cancer cell line derived from a simple carcinoma. The cell line CMT-U27 was grown in 96-well plates, at two cell densities (4 × 103 and 8 × 103 cells/well). Cultures were treated with oxytocin (OT) or desmopressin at five concentrations (10, 50, 100, 500, and 1000 nM). After 72 h of incubation, cell proliferation was determined by the MTT assay. Results showed that with 4 × 103 cells/well, OT at 50, 500, and 1000 nM was growth inhibitory for the cells, being statistically significant at 1000 nM. On the contrary, no antiproliferative effect was observed with 10 or 100 nM. At 8 × 103 cells/well, OT showed a significant antiproliferative effect only with the highest concentration (1000 nM). Desmopressin at 4 × 103 cells/well decreased cell viability at concentrations of 50, 100, 500, and 1000 nM (statistically significant with the highest concentration), while no effect was observed with 10 nM. With 8 × 103 cells/well, this peptide reduced cell growth at 100, 500, and 1000 nM. In conclusion, we suggest that these peptides may be potential and promising compounds for the treatment of dogs with simple carcinomas of the mammary gland. In vivo studies are required to confirm this hypothesis. PMID:28083539

  17. Antiproliferative Effects of Oxytocin and Desmopressin on Canine Mammary Cancer Cells.

    PubMed

    Benavente, Micaela Andrea; Bianchi, Carolina Paula; Imperiale, Fernanda; Aba, Marcelo Alfredo

    2016-01-01

    Neoplasms of the mammary gland represent the most frequent tumor type in the female dog, and according to the histologic criteria, approximately 50% of them are malignant. In the most aggressive cases of mammary cancer, surgery is not enough to warrant a favorable outcome, and adjuvant therapies are needed to improve the patient's overall survival. The aim of the present study was to evaluate the effects of two peptides on proliferation of a canine mammary cancer cell line derived from a simple carcinoma. The cell line CMT-U27 was grown in 96-well plates, at two cell densities (4 × 10 3 and 8 × 10 3 cells/well). Cultures were treated with oxytocin (OT) or desmopressin at five concentrations (10, 50, 100, 500, and 1000 nM). After 72 h of incubation, cell proliferation was determined by the MTT assay. Results showed that with 4 × 10 3 cells/well, OT at 50, 500, and 1000 nM was growth inhibitory for the cells, being statistically significant at 1000 nM. On the contrary, no antiproliferative effect was observed with 10 or 100 nM. At 8 × 10 3 cells/well, OT showed a significant antiproliferative effect only with the highest concentration (1000 nM). Desmopressin at 4 × 10 3 cells/well decreased cell viability at concentrations of 50, 100, 500, and 1000 nM (statistically significant with the highest concentration), while no effect was observed with 10 nM. With 8 × 10 3 cells/well, this peptide reduced cell growth at 100, 500, and 1000 nM. In conclusion, we suggest that these peptides may be potential and promising compounds for the treatment of dogs with simple carcinomas of the mammary gland. In vivo studies are required to confirm this hypothesis.

  18. Does ultrasonography accurately diagnose acute cholecystitis? Improving diagnostic accuracy based on a review at a regional hospital

    PubMed Central

    Hwang, Hamish; Marsh, Ian; Doyle, Jason

    2014-01-01

    Background Acute cholecystitis is one of the most common diseases requiring emergency surgery. Ultrasonography is an accurate test for cholelithiasis but has a high false-negative rate for acute cholecystitis. The Murphy sign and laboratory tests performed independently are also not particularly accurate. This study was designed to review the accuracy of ultrasonography for diagnosing acute cholecystitis in a regional hospital. Methods We studied all emergency cholecystectomies performed over a 1-year period. All imaging studies were reviewed by a single radiologist, and all pathology was reviewed by a single pathologist. The reviewers were blinded to each other’s results. Results A total of 107 patients required an emergency cholecystectomy in the study period; 83 of them underwent ultrasonography. Interradiologist agreement was 92% for ultrasonography. For cholelithiasis, ultrasonography had 100% sensitivity, 18% specificity, 81% positive predictive value (PPV) and 100% negative predictive value (NPV). For acute cholecystitis, it had 54% sensitivity, 81% specificity, 85% PPV and 47% NPV. All patients had chronic cholecystitis and 67% had acute cholecystitis on histology. When combined with positive Murphy sign and elevated neutrophil count, an ultrasound showing cholelithiasis or acute cholecystitis yielded a sensitivity of 74%, specificity of 62%, PPV of 80% and NPV of 53% for the diagnosis of acute cholecystitis. Conclusion Ultrasonography alone has a high rate of false-negative studies for acute cholecystitis. However, a higher rate of accurate diagnosis can be achieved using a triad of positive Murphy sign, elevated neutrophil count and an ultrasound showing cholelithiasis or cholecystitis. PMID:24869607

  19. The epigenetic landscape of mammary gland development and functional differentiation

    USDA-ARS?s Scientific Manuscript database

    Most of the development and functional differentiation in the mammary gland occur after birth. Epigenetics is defined as the stable alterations in gene expression potential that arise during development and proliferation. Epigenetic changes are mediated at the biochemical level by the chromatin conf...

  20. Ethanol potentiates the genotoxicity of the food-derived mammary carcinogen PhIP in human estrogen receptor-positive mammary cells: mechanistic support for lifestyle factors (cooked red meat and ethanol) associated with mammary cancer.

    PubMed

    Malik, Durr-E-Shahwar; David, Rhiannon M; Gooderham, Nigel J

    2018-04-01

    Consumption of cooked/processed meat and ethanol are lifestyle risk factors in the aetiology of breast cancer. Cooking meat generates heterocyclic amines such as 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Epidemiology, mechanistic and animal studies indicate that PhIP is a mammary carcinogen that could be causally linked to breast cancer incidence; PhIP is DNA damaging, mutagenic and oestrogenic. PhIP toxicity involves cytochrome P450 (CYP1 family)-mediated metabolic activation to DNA-damaging species, and transcriptional responses through Aryl hydrocarbon receptor (AhR) and estrogen-receptor-α (ER-α). Ethanol consumption is a modifiable lifestyle factor strongly associated with breast cancer risk. Ethanol toxicity involves alcohol dehydrogenase metabolism to reactive acetaldehyde, and is also a substrate for CYP2E1, which when uncoupled generates reactive oxygen species (ROS) and DNA damage. Here, using human mammary cells that differ in estrogen-receptor status, we explore genotoxicity of PhIP and ethanol and mechanisms behind this toxicity. Treatment with PhIP (10 -7 -10 -4 M) significantly induced genotoxicity (micronuclei formation) preferentially in ER-α positive human mammary cell lines (MCF-7, ER-α+) compared to MDA-MB-231 (ER-α-) cells. PhIP-induced CYP1A2 in both cell lines but CYP1B1 was selectively induced in ER-α(+) cells. ER-α inhibition in MCF-7 cells attenuated PhIP-mediated micronuclei formation and CYP1B1 induction. PhIP-induced CYP2E1 and ROS via ER-α-STAT-3 pathway, but only in ER-α (+) MCF-7 cells. Importantly, simultaneous treatments of physiological concentrations ethanol (10 -3 -10 -1 M) with PhIP (10 -7 -10 -4 M) increased oxidative stress and genotoxicity in MCF-7 cells, compared to the individual chemicals. Collectively, these data offer a mechanistic basis for the increased risk of breast cancer associated with dietary cooked meat and ethanol lifestyle choices.

  1. Hormone-induced protection against mammary tumorigenesis is conserved in multiple rat strains and identifies a core gene expression signature induced by pregnancy.

    PubMed

    Blakely, Collin M; Stoddard, Alexander J; Belka, George K; Dugan, Katherine D; Notarfrancesco, Kathleen L; Moody, Susan E; D'Cruz, Celina M; Chodosh, Lewis A

    2006-06-15

    Women who have their first child early in life have a substantially lower lifetime risk of breast cancer. The mechanism for this is unknown. Similar to humans, rats exhibit parity-induced protection against mammary tumorigenesis. To explore the basis for this phenomenon, we identified persistent pregnancy-induced changes in mammary gene expression that are tightly associated with protection against tumorigenesis in multiple inbred rat strains. Four inbred rat strains that exhibit marked differences in their intrinsic susceptibilities to carcinogen-induced mammary tumorigenesis were each shown to display significant protection against methylnitrosourea-induced mammary tumorigenesis following treatment with pregnancy levels of estradiol and progesterone. Microarray expression profiling of parous and nulliparous mammary tissue from these four strains yielded a common 70-gene signature. Examination of the genes constituting this signature implicated alterations in transforming growth factor-beta signaling, the extracellular matrix, amphiregulin expression, and the growth hormone/insulin-like growth factor I axis in pregnancy-induced alterations in breast cancer risk. Notably, related molecular changes have been associated with decreased mammographic density, which itself is strongly associated with decreased breast cancer risk. Our findings show that hormone-induced protection against mammary tumorigenesis is widely conserved among divergent rat strains and define a gene expression signature that is tightly correlated with reduced mammary tumor susceptibility as a consequence of a normal developmental event. Given the conservation of this signature, these pathways may contribute to pregnancy-induced protection against breast cancer.

  2. Megalin-Mediated Endocytosis of Vitamin D Binding Protein Correlates with 25-Hydroxycholecalciferol Actions in Human Mammary Cells1

    PubMed Central

    Rowling, Matthew J.; Kemmis, Carly M.; Taffany, David A.; Welsh, JoEllen

    2007-01-01

    The major circulating form of vitamin D is 25-hydroxycholecalciferol [25(OH)D3], which is delivered to target tissues in complex with the serum vitamin D binding protein (DBP). We recently observed that mammary cells can metabolize 25(OH)D3 to 1,25-dihydroxycholecalciferol [1,25(OH)2D3], the vitamin D receptor (VDR) ligand, and the objective of our study was to elucidate the mechanisms by which the 25(OH)D3-DBP complex is internalized by mammary cells prior to metabolism. Using fluorescent microscopy and temperature-shift techniques, we found that T-47D breast cancer cells rapidly internalize DBP via endocytosis, which is blunted by receptor-associated protein, a specific inhibitor of megalin-mediated endocytosis. Endocytosis of DBP was associated with activation of VDR by 25(OH)D3 but not 1,25(OH)2D3 (as measured by induction of the VDR target gene, CYP24). We also found that megalin and its endocytic partner, cubilin, are coexpressed in normal murine mammary tissue, in nontransformed human mammary epithelial cell lines, and in some established human breast cancer cell lines. To our knowledge, our studies are the first to demonstrate that mammary-derived cells express megalin and cubilin, which contribute to the endocytic uptake of 25(OH)D3-DBP and activation of the VDR pathway. PMID:17056796

  3. Effect of dietary protein quality and feeding level on milk secretion and mammary protein synthesis in the rat

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sampson, D.A.; Jansen, G.R.

    1985-04-01

    Protein synthesis was studied in mammary tissue of rats fed diets deficient in protein quality and/or restricted in food intake throughout gestation and lactation. Diets containing 25% wheat gluten (WG), wheat gluten plus lysine and threonine (WGLT), or casein (C) were pair-fed from conception until day 15 of lactation at 100% or 85% of WG ad libitum consumption (PF100 and PF85, respectively). A seventh group was fed C ad libitum. Rates of protein synthesis were measured in vivo at day 15 of lactation from incorporation of (3-/sup 3/H)phenylalanine. At both PF100 and PF85, fractional and absolute rates of mammary glandmore » protein synthesis were two- to three-fold higher in rats fed C than in those fed WG. Pup weights showed similar treatment effects. Both mammary protein synthesis rates and pup weights were significantly higher in rats fed C at PF85 than rats fed WG ad libitum. Food restriction from PF100 to PF85 depressed pup weights and mammary protein synthesis rates in rats fed WGLT, but had no effect in rats fed WG. These results demonstrate that when food intake is restricted, improvement of protein quality of the maternal diet increases milk output in the rat in association with increased rates of mammary protein synthesis.« less

  4. Cost-effectiveness analysis of ultrasonography screening for nonalcoholic fatty liver disease in metabolic syndrome patients.

    PubMed

    Phisalprapa, Pochamana; Supakankunti, Siripen; Charatcharoenwitthaya, Phunchai; Apisarnthanarak, Piyaporn; Charoensak, Aphinya; Washirasaksiri, Chaiwat; Srivanichakorn, Weerachai; Chaiyakunapruk, Nathorn

    2017-04-01

    Nonalcoholic fatty liver disease (NAFLD) can be diagnosed early by noninvasive ultrasonography; however, the cost-effectiveness of ultrasonography screening with intensive weight reduction program in metabolic syndrome patients is not clear. This study aims to estimate economic and clinical outcomes of ultrasonography in Thailand. Cost-effectiveness analysis used decision tree and Markov models to estimate lifetime costs and health benefits from societal perspective, based on a cohort of 509 metabolic syndrome patients in Thailand. Data were obtained from published literatures and Thai database. Results were reported as incremental cost-effectiveness ratios (ICERs) in 2014 US dollars (USD) per quality-adjusted life year (QALY) gained with discount rate of 3%. Sensitivity analyses were performed to assess the influence of parameter uncertainty on the results. The ICER of ultrasonography screening of 50-year-old metabolic syndrome patients with intensive weight reduction program was 958 USD/QALY gained when compared with no screening. The probability of being cost-effective was 67% using willingness-to-pay threshold in Thailand (4848 USD/QALY gained). Screening before 45 years was cost saving while screening at 45 to 64 years was cost-effective. For patients with metabolic syndromes, ultrasonography screening for NAFLD with intensive weight reduction program is a cost-effective program in Thailand. Study can be used as part of evidence-informed decision making. Findings could contribute to changes of NAFLD diagnosis practice in settings where economic evidence is used as part of decision-making process. Furthermore, study design, model structure, and input parameters could also be used for future research addressing similar questions.

  5. Mammary candidiasis: molecular-based detection of Candida species in human milk samples.

    PubMed

    Mutschlechner, W; Karall, D; Hartmann, C; Streiter, B; Baumgartner-Sigl, S; Orth-Höller, D; Lass-Flörl, C

    2016-08-01

    In this prospective and monocentric study, we investigated the performance of a commercialized real-time polymerase chain reaction (RT-PCR) test system for the specific detection of DNA from Candida albicans, C. dubliniensis, C. glabrata, C. krusei, C. lusitaniae, C. parapsilosis, and C. tropicalis in human milk samples of patients suspicious of mammary candidiasis. For this purpose, 43 breast-feeding women with characteristic symptoms of mammary candidiasis and 40 asymptomatic controls were enrolled. By culture, Candida spp. were detected in 8.8 % (4/46) and 9.3 % (4/43) of patient and control samples, respectively. Candida albicans (2/46), C. parapsilosis (1/46), and C. guilliermondii (1/46) were present in patient samples, and C. lusitaniae (3/43) and C. guilliermondii (1/43) were present in the controls. After RT-PCR was applied, Candida spp. were found to be present in 67.4 % (31/46) and 79.1 % (34/43) of patient and control samples investigated, respectively. PCR detection of C. albicans and C. parapsilosis revealed only a low sensitivity and specificity of 67.4 % and 41.9 %, respectively. Our data do not support the use of Candida RT-PCR for sensitive and specific diagnosis of mammary candidiasis.

  6. Role of ultrasonography in the differential diagnosis of thyrotoxicosis: a noninvasive, cost-effective, and widely available but underutilized diagnostic tool.

    PubMed

    Alzahrani, Ali S; Ceresini, Graziano; Aldasouqi, Saleh A

    2012-01-01

    To explore the use of ultrasonography as a diagnostic alternative to the traditional "gold standard" imaging study of nuclear scintigraphy in the evaluation of thyrotoxicosis. We review the relevant literature and share our own experience to highlight the promising role of ultrasonography in thyrotoxicosis. In addition, we present a diagnostic algorithm suggesting liberal use of ultrasonography in the evaluation of thyrotoxicosis. Ultrasonography has proved effective not only in the differentiation of Graves disease from other types and causes of thyrotoxicosis but also in the detection of subtle thyroid nodules. The latter role is emphasized in light of the recent observation of an increased risk of occurrence of papillary thyroid carcinoma in patients with Graves disease. Ultrasonography is a cost-effective, noninvasive, portable, and safe imaging modality in the evaluation of thyrotoxicosis, both for physiologic assessment and for detection of nonpalpable thyroid cancers that may elude identification on physical examination and nuclear imaging studies. Although thyroid scintigraphy remains a standard radiologic study, thyroid ultrasonography can be a practical alternative in many cases and the primary imaging modality in some situations such as during pregnancy and lactation and for evaluation and management of amiodarone-induced thyrotoxicosis.

  7. Effect of protein quality on /sup 14/C glucose utilization in isolated rat mammary acini

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Masor, M.L.; Grundleger, M.L.; Jansen, G.R.

    1986-03-01

    Poor protein quality has a deleterious effect on lactation in rats. Dams consuming a 13% wheat gluten (WG) diet are unable to maintain litters. Glucose utilization in isolated mammary acini taken from dams at either day 20 of gestation (G20) or day 4 of lactation (L4) was examined in dams consuming 13% WG vs 13% casein-methionine (CM) diets from day of breeding. Dams consuming WG had significantly smaller inguinal-abdominal mammary glands than CM dams at both G20 and L4, and mammary glands of CM but not WG dams were larger at L4 than G20. Both average pup weight and pupmore » daily gain were smaller in WG litters. Basal levels of /sup 14/C glucose oxidation (GO) and /sup 14/C glucose incorporation into lipid (GL) and lactose were examined. A large significant increase in GO and GL occurred in CM dams from G20 to L4 but not in WG dams. Both GO and GL were higher in CM dams on L4 but not at G20. The ratio of GO:GO+GL changed at parturition in CM but not WG dams. The normal changes in glucose utilization by mammary epithelial cells which occur at parturition were impaired by the WG diet.« less

  8. “Nodule in Nodule” on Thyroid Ultrasonography: Possibility of Follicular Carcinoma Transformed from Benign Thyroid Tumor

    PubMed Central

    Kobayashi, Kaoru; Ota, Hisashi; Hirokawa, Mitsuyoshi; Yabuta, Tomonori; Fukushima, Mitsuhiro; Masuoka, Hiroo; Higashiyama, Takuya; Kihara, Minoru; Ito, Yasuhiro; Miya, Akihiro; Miyauchi, Akira

    2017-01-01

    Background It is generally considered impossible to differentiate follicular carcinomas from follicular adenomas by means of ultrasonography or cytology before surgery. Therefore, follicular carcinoma is histopathologically diagnosed by verifying capsular and/or vascular invasion after surgery. However, ultrasonography may play an important role in diagnosing follicular carcinoma preoperatively in a small number of cases. Case Description Four cases of follicular carcinoma or follicular neoplasm that transformed from a benign thyroid tumor and demonstrated a “nodule in nodule” appearance on ultrasonography are presented in this report. Characteristic ultrasound features of such patients are: (1) a “nodule in nodule” appearance, (2) a well-defined boundary line between the nodules, and (3) separate distribution of blood signals within each nodule. Conclusion A small number of patients with follicular carcinomas or follicular neoplasms may present with a “nodule in nodule” appearance on ultrasonography. It was suggested a long time ago that follicular carcinomas may develop from benign thyroid tumors. The fact that follicular carcinomas appear within benign tumors may be evidence of thyroid tumorigenesis. PMID:28589092

  9. Enhancement of NAD+-dependent SIRT1 deacetylase activity by methylselenocysteine resets the circadian clock in carcinogen-treated mammary epithelial cells

    PubMed Central

    Fang, Mingzhu; Guo, Wei-Ren; Park, Youngil; Kang, Hwan-Goo; Zarbl, Helmut

    2015-01-01

    We previously reported that dietary methylselenocysteine (MSC) inhibits N-methyl-N-nitrosourea (NMU)-induced mammary tumorigenesis by resetting circadian gene expression disrupted by the carcinogen at the early stage of tumorigenesis. To investigate the underlying mechanism, we developed a circadian reporter system comprised of human mammary epithelial cells with a luciferase reporter driven by the promoter of human PERIOD 2 (PER2), a core circadian gene. In this in vitro model, NMU disrupted cellular circadian rhythm in a pattern similar to that observed with SIRT1-specific inhibitors; in contrast, MSC restored the circadian rhythms disrupted by NMU and protected against SIRT1 inhibitors. Moreover, NMU inhibited intracellular NAD+/NADH ratio and reduced NAD+-dependent SIRT1 activity in a dose-dependent manner, while MSC restored NAD+/NADH and SIRT1 activity in the NMU-treated cells, indicating that the NAD+-SIRT1 pathway was targeted by NMU and MSC. In rat mammary tissue, a carcinogenic dose of NMU also disrupted NAD+/NADH oscillations and decreased SIRT1 activity; dietary MSC restored NAD+/NADH oscillations and increased SIRT1 activity in the mammary glands of NMU-treated rats. MSC-induced SIRT1 activity was correlated with decreased acetylation of BMAL1 and increased acetylation of histone 3 lysine 9 at the Per2 promoter E-Box in mammary tissue. Changes in SIRT1 activity were temporally correlated with loss or restoration of rhythmic Per2 mRNA expression in NMU-treated or MSC-rescued rat mammary glands, respectively. Together with our previous findings, these results suggest that enhancement of NAD+-dependent SIRT1 activity contributes to the chemopreventive efficacy of MSC by restoring epigenetic regulation of circadian gene expression at early stages of mammary tumorigenesis. PMID:26544624

  10. The effectiveness of ultrasonography in verifying the placement of a nasogastric tube in patients with low consciousness at an emergency center

    PubMed Central

    2012-01-01

    Background This study was designed to compare the effectiveness of using auscultation, pH measurements of gastric aspirates, and ultrasonography as physical examination methods to verify nasogastric tube(NGT) placement in emergency room patients with low consciousness who require NGT insertion. Methods The study included 47 patients who were all over 18 years of age. In all patients, tube placement was verified by chest X-rays. Auscultation, pH analysis of gastric aspirates, and ultrasonography were conducted on each patient in random order. The mean patient age was 57.62 ± 17.24 years, and 28 males (59.6%) and 19 females (40.4%) were included. The NGT was inserted by an emergency room resident. For pH testing, gastric aspirates were dropped onto litmus paper, and the resulting color of the paper was compared with a reference table. Ultrasonography was performed by an emergency medicine specialist, and the chest X-ray examination was interpreted by a different emergency medicine specialist who did not conduct the ultrasonography test. The results of the auscultation, gastric aspirate pH, and ultrasonography examinations were compared with the results of the chest x-ray examination. Results The sensitivity and specificity were 100% and 33.3%, respectively, for auscultation and 86.4% and 66.7%, respectively, for ultrasonography. Kappa values were the highest for auscultation at 0.484 compared to chest x-rays, followed by 0.299 for ultrasonography and 0.444 for pH analysis of the gastric aspirate. The ultrasonography has a positive predictive value of 97.4% and a negative predictive value of 25%. Conclusions Ultrasonography is useful for confirming the results of auscultation after NGT insertion among patients with low consciousness at an emergency center. When ultrasound findings suggest that the NGT placement is not gastric, additional chest X-ray should be performed. PMID:22691418

  11. The effectiveness of ultrasonography in verifying the placement of a nasogastric tube in patients with low consciousness at an emergency center.

    PubMed

    Kim, Hyung Min; So, Byung Hak; Jeong, Won Jung; Choi, Se Min; Park, Kyu Nam

    2012-06-12

    This study was designed to compare the effectiveness of using auscultation, pH measurements of gastric aspirates, and ultrasonography as physical examination methods to verify nasogastric tube(NGT) placement in emergency room patients with low consciousness who require NGT insertion. The study included 47 patients who were all over 18 years of age. In all patients, tube placement was verified by chest X-rays. Auscultation, pH analysis of gastric aspirates, and ultrasonography were conducted on each patient in random order. The mean patient age was 57.62 ± 17.24 years, and 28 males (59.6%) and 19 females (40.4%) were included. The NGT was inserted by an emergency room resident. For pH testing, gastric aspirates were dropped onto litmus paper, and the resulting color of the paper was compared with a reference table. Ultrasonography was performed by an emergency medicine specialist, and the chest X-ray examination was interpreted by a different emergency medicine specialist who did not conduct the ultrasonography test. The results of the auscultation, gastric aspirate pH, and ultrasonography examinations were compared with the results of the chest x-ray examination. The sensitivity and specificity were 100% and 33.3%, respectively, for auscultation and 86.4% and 66.7%, respectively, for ultrasonography. Kappa values were the highest for auscultation at 0.484 compared to chest x-rays, followed by 0.299 for ultrasonography and 0.444 for pH analysis of the gastric aspirate. The ultrasonography has a positive predictive value of 97.4% and a negative predictive value of 25%. Ultrasonography is useful for confirming the results of auscultation after NGT insertion among patients with low consciousness at an emergency center. When ultrasound findings suggest that the NGT placement is not gastric, additional chest X-ray should be performed.

  12. Comparing Magnetic Resonance Imaging and High-Resolution Dynamic Ultrasonography for Diagnosis of Plantar Plate Pathology: A Case Series.

    PubMed

    Donegan, Ryan J; Stauffer, Anthony; Heaslet, Michael; Poliskie, Michael

    Plantar plate pathology has gained noticeable attention in recent years as an etiology of lesser metatarsophalangeal joint pain. The heightened clinical awareness has led to the need for more effective diagnostic imaging accuracy. Numerous reports have established the accuracy of both magnetic resonance imaging and ultrasonography for the diagnosis of plantar plate pathology. However, no conclusions have been made regarding which is the superior imaging modality. The present study reports a case series directly comparing high-resolution dynamic ultrasonography and magnetic resonance imaging. A multicenter retrospective comparison of magnetic resonance imaging versus high-resolution dynamic ultrasonography to evaluate plantar plate pathology with surgical confirmation was conducted. The sensitivity, specificity, and positive and negative predictive values for magnetic resonance imaging were 60%, 100%, 100%, and 33%, respectively. The overall diagnostic accuracy compared with the intraoperative findings was 66%. The sensitivity, specificity, and positive and negative predictive values for high-resolution dynamic ultrasound imaging were 100%, 100%, 100%, and 100%, respectively. The overall diagnostic accuracy compared with the intraoperative findings was 100%. The p value using Fisher's exact test for magnetic resonance imaging and high-resolution dynamic ultrasonography was p = .45, a difference that was not statistically significant. High-resolution dynamic ultrasonography had greater accuracy than magnetic resonance imaging in diagnosing lesser metatarsophalangeal joint plantar plate pathology, although the difference was not statistically significant. The present case series suggests that high-resolution dynamic ultrasonography can be considered an equally accurate imaging modality for plantar plate pathology at a potential cost savings compared with magnetic resonance imaging. Therefore, high-resolution dynamic ultrasonography warrants further investigation in

  13. Lactic Acid Bacteria Isolated from Bovine Mammary Microbiota: Potential Allies against Bovine Mastitis.

    PubMed

    Bouchard, Damien S; Seridan, Bianca; Saraoui, Taous; Rault, Lucie; Germon, Pierre; Gonzalez-Moreno, Candelaria; Nader-Macias, Fatima M E; Baud, Damien; François, Patrice; Chuat, Victoria; Chain, Florian; Langella, Philippe; Nicoli, Jacques; Le Loir, Yves; Even, Sergine

    2015-01-01

    Bovine mastitis is a costly disease in dairy cattle worldwide. As of yet, the control of bovine mastitis is mostly based on prevention by thorough hygienic procedures during milking. Additional strategies include vaccination and utilization of antibiotics. Despite these measures, mastitis is not fully under control, thus prompting the need for alternative strategies. The goal of this study was to isolate autochthonous lactic acid bacteria (LAB) from bovine mammary microbiota that exhibit beneficial properties that could be used for mastitis prevention and/or treatment. Sampling of the teat canal led to the isolation of 165 isolates, among which a selection of ten non-redundant LAB strains belonging to the genera Lactobacillus and Lactococcus were further characterized with regard to several properties: surface properties (hydrophobicity, autoaggregation); inhibition potential of three main mastitis pathogens, Staphylococcus aureus, Escherichia coli and Streptococcus uberis; colonization capacities of bovine mammary epithelial cells (bMEC); and immunomodulation properties. Three strains, Lactobacillus brevis 1595 and 1597 and Lactobacillus plantarum 1610, showed high colonization capacities and a medium surface hydrophobicity. These strains are good candidates to compete with pathogens for mammary gland colonization. Moreover, nine strains exhibited anti-inflammatory properties, as illustrated by the lower IL-8 secretion by E. coli-stimulated bMEC in the presence of these LAB. Full genome sequencing of five candidate strains allowed to check for undesirable genetic elements such as antibiotic resistance genes and to identify potential bacterial determinants involved in the beneficial properties. This large screening of beneficial properties while checking for undesirable genetic markers allowed the selection of promising candidate LAB strains from bovine mammary microbiota for the prevention and/or treatment of bovine mastitis.

  14. Genotoxic Exposure during Juvenile Growth of Mammary Gland Depletes Stem Cell Activity and Inhibits Wnt Signaling

    PubMed Central

    Klos, Kristine S.; Kim, Soyoung; Alexander, Caroline M.

    2012-01-01

    Various types of somatic stem cell have been tested for their response to genotoxic exposure, since these cells are likely to be important to regeneration, aging and cancer. In this study, we evaluated the response of mammary stem cells to genotoxic exposure during ductal growth in juveniles. Exposure to the polycyclic aromatic hydrocarbon (DMBA; 7,12 dimethylbenz[a]anthracene) had no gross effect on outgrowth and morphogenesis of the ductal tree, or upon lobuloalveolar growth during pregnancy. However, by fat pad assay, we found that mammary stem cell activity was reduced by 80% in glands from adults that were exposed to genotoxins as juveniles. The associated basal cell lineage was depleted. Both basal and luminal cells showed a robust response to genotoxic exposure (including γH2AX phosphorylation, pS15p53 and pT68Chk2), with durable hyperproliferation, but little cytotoxicity. Since the phenotype of these glands (low basal cell fraction, low stem cell activity) phenocopies mammary glands with loss of function for Wnt signaling, we measured Wnt signaling in genotoxin-exposed glands, and found a durable reduction in the activation of the canonical signaling Wnt receptors, Lrp5/6. Furthermore, when mammary epithelial cells were treated with Wnt3a, DMBA exposure reduced the basal cell population and Lrp activation was ablated. We conclude that during active ductal growth, Wnt-dependent mammary stem cells are sensitized to cell death by genotoxin exposure. Our conclusion may be important for other tissues, since all solid tumor stem cell activities have been shown to be Wnt-dependent to date. PMID:23185480

  15. Return to contact sports following infectious mononucleosis: the role of serial ultrasonography.

    PubMed

    O'Connor, Tony E; Skinner, Liam J; Kiely, Patrick; Fenton, John E

    2011-08-01

    Splenic rupture is a rare but potentially fatal complication of infectious mononucleosis. Athletes returning to contact sports following infectious mononucleosis are at potential risk of splenic rupture secondary to abdominal trauma. No clear consensus exists as to when it is safe to allow these athletes to return to contact sports. Suggested periods of abstinence have ranged from 2 weeks to 6 months. We outline our experiences with the use of abdominal ultrasonography at 1 month after the diagnosis of infectious mononucleosis as a means of determining when athletes can safely return to contact sports. Our study group was made up of 19 such patients (mean age: 16.7 yr). We found that 16 of these patients (84%) had normal splenic dimensions on ultrasonography 1 month after diagnosis, and they were therefore allowed to return to contact sports. While the remaining 3 patients had an enlarged spleen at 1 month, their splenic dimensions had all returned to normal when ultrasonographic examination was repeated at 2 months postdiagnosis. We conclude that serial abdominal ultrasonography allows for informed decision making in determining when athletes can safely return to contact sports following infectious mononucleosis.

  16. Diagnostic Accuracy of Ultrasonography and Radiography in Initial Evaluation of Chest Trauma Patients.

    PubMed

    Vafaei, Ali; Hatamabadi, Hamid Reza; Heidary, Kamran; Alimohammadi, Hosein; Tarbiyat, Mohammad

    2016-01-01

    Application of chest radiography for all multiple trauma patients is associated with a significant increase in total costs, exposure to radiation, and overcrowding of the emergency department. Ultrasound has been introduced as an alternative diagnostic tool in this regard. The aim of the present study is to compare the diagnostic accuracy of chest ultrasonography and radiography in detection of traumatic intrathoracic injuries. In the present prospective cross-sectional study, patients with traumatic intrathoracic injuries, who were referred to the emergency department from December 2013 to December 2014, were assessed. The patients underwent bedside ultrasound, radiographic and computed tomography (CT) scan examinations based on ATLS recommendations. Screening performance characteristics of ultrasonography and radiography were compared using SPSS 21.0. Chest CT scan was considered as gold standard. 152 chest trauma patients with a mean age of 31.4 ± 13.8 years (range: 4 ‒ 67), were enrolled (77.6% male). Chest CT scan showed pulmonary contusion in 48 (31.6%) patients, hemothorax in 29 (19.1%), and pneumothorax in 55 (36.2%) cases. Area under the ROC curve of ultrasonography in detection of pneumothorax, hemothorax, and pulmonary contusion were 0.91 (95% CI: 0.86‒0.96), 0.86 (95% CI: 0.78‒0.94), and 0.80 (95% CI: 0.736‒0.88), respectively. Area under the ROC curve of radiography was 0.80 (95% CI: 0.736‒0.87) for detection of pneumothorax, 0.77 (95% CI: 0.68‒0.86) for hemothorax, and 0.58 (95% CI: 0.5‒0.67) for pulmonary contusion. Comparison of areas under the ROC curve declared the significant superiority of ultrasonography in detection of pneumothorax (p = 0.02) and pulmonary contusion (p < 0.001). However, the diagnostic value of the two tests was equal in detection of hemothorax (p = 0.08). The results of the present study showed that ultrasonography is preferable to radiography in the initial evaluation of patients with traumatic injuries to the

  17. Purification of PRL receptors from toad kidney: Comparisons with rabbit mammary PRL receptors

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dunand, M.; Kraehenbuhl, J.P.; Rossier, B.C.

    1988-03-01

    The binding characteristics of the prolactin (PRL) receptors present in toad (Bufo marinus) kidneys were investigated and compared to those of PRL receptors present in rabbit mammary glands. The molecular characteristics of the Triton X-100 solubilized renal and mammary PRL receptors were assessed by gel filtration and by migration analysis on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) after affinity labeling of the binding sites with {sup 125}I-human growth hormone. Similar results were obtained for both receptors. Partial purification of the toad PRL receptor could be achieved by affinity chromatography. The molecular weight of this purified receptor could be determined bymore » analysis of SDS-PAGE. With the use of a polyclonal antiserum raised against a purified preparation of rabbit mammary PRL receptor, one or several antigenic epitope(s) could be identified on the core of the toad renal PRL receptor. In conclusion, although the structure and the biological role(s) of PRL have substantially changed during evolution, the receptor for this hormone has retained many of its structural features as could be assessed between an amphibian and a mammalian species on functionally different target tissues.« less

  18. High-resolution ultrasonography in assessing temporomandibular joint disc position.

    PubMed

    Talmaceanu, Daniel; Lenghel, Lavinia Manuela; Bolog, Nicolae; Popa Stanila, Roxana; Buduru, Smaranda; Leucuta, Daniel Corneliu; Rotar, Horatiu; Baciut, Mihaela; Baciut, Grigore

    2018-02-04

    The purpose of this study was to determine the diagnostic value of high-resolution ultrasonography (US) in temporomandibular joint (TMJ) disc displacements. A number of 74 patients (148 TMJs) with signs and symptoms of TMJ disorders, according to the Research Diagnostic Criteria for Temporomandibular Disorders, were included in this study. All patients received US and magnetic resonance imaging (MRI) of both TMJs 1 to 5 days after the clinical examination. MRI examinations were performed using 1.5 T MRI equipment (Siemens Avanto, Siemens, Erlangen). Ultrasonographic examination was performed on a Hitachi EUB 8500 (Hitachi Medical Corp., Tokyo, Japan) scanner with L 54 M6.5-13 MHz linear transducer. MRI depicted 68 (45.95%) normal joints, 47 (31.76%) with disc displacement with reduction, 33 (22.3%) with disc displacement without reduction and 34 (22.97%) with degenerative changes. US detected 78 (52.7%) normal joints, 37 (25%) with disc displacement with reduction, 33 (22.3%) with disc displacement without reduction and 21 (14.19%) with degenerative changes. Compared to MRI, US showed a sensitivity of 93.1%, specificity of 87.88%, accuracy of 90.32%, a positive predictive value of 87.1% and a negative predictive value of 93.55% for overall diagnosis of disc displacement. The Youden index was 0.81. Based on our results, high-resolution ultrasonography showed high sensitivity, specificity and accuracy in the diagnosis of TMJ disc displacement. It could be a valuable imaging technique in assessing TMJ disc position. The diagnostic value of high-resolution ultrasonography depends strictly on the examiner's skills and on the equipment used.

  19. Doppler ultrasonography of the pectinis oculi artery in harpy eagles (Harpia harpyja)

    PubMed Central

    de Moraes, Wanderlei; Ferreira, Thiago A.C.; Somma, André T.; Cubas, Zalmir S.; Moore, Bret A.; Montiani-Ferreira, Fabiano

    2017-01-01

    Twenty harpy eagles (Harpia harpyja) without systemic or ocular diseases were examined to measure blood velocity parameters of the pectinis oculi artery using Doppler ultrasonography. Pectinate artery resistive index (RI) and pulsatility index (PI) were investigated using ocular Doppler ultrasonography. The mean RI and PI values across all eyes were 0.44±0.10 and 0.62±0.20 respectively. Low RI and PI values found in the harpy eagle´s pectinis oculi artery compared with the American pekin ducks one and other tissue suggest indeed a high metabolic activity in pecten oculi and corroborates the hypothesis of a nutritional function and/or intraocular pressure regulation. PMID:28540254

  20. Paracrine Met signaling triggers epithelial–mesenchymal transition in mammary luminal progenitors, affecting their fate

    PubMed Central

    Di-Cicco, Amandine; Petit, Valérie; Chiche, Aurélie; Bresson, Laura; Romagnoli, Mathilde; Orian-Rousseau, Véronique; Vivanco, Maria dM; Medina, Daniel; Faraldo, Marisa M; Glukhova, Marina A; Deugnier, Marie-Ange

    2015-01-01

    HGF/Met signaling has recently been associated with basal-type breast cancers, which are thought to originate from progenitor cells residing in the luminal compartment of the mammary epithelium. We found that ICAM-1 efficiently marks mammary luminal progenitors comprising hormone receptor-positive and receptor-negative cells, presumably ductal and alveolar progenitors. Both cell populations strongly express Met, while HGF is produced by stromal and basal myoepithelial cells. We show that persistent HGF treatment stimulates the clonogenic activity of ICAM1-positive luminal progenitors, controlling their survival and proliferation, and leads to the expression of basal cell characteristics, including stem cell potential. This is accompanied by the induction of Snai1 and Snai2, two major transcription factors triggering epithelial–mesenchymal transition, the repression of the luminal-regulatory genes Elf5 and Hey1, and claudin down-regulation. Our data strongly indicate that paracrine Met signaling can control the function of luminal progenitors and modulate their fate during mammary development and tumorigenesis. DOI: http://dx.doi.org/10.7554/eLife.06104.001 PMID:26165517