Sample records for accelerates mammary tumorprogression

  1. Activated type I TGFbeta receptor (Alk5) kinase confers enhancedsurvival to mammary epithelial cells and accelerates mammary tumorprogression

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    Muraoka-Cook, Rebecca S.; Shin, Incheol; Yi, Jae Youn; Easterly,Evangeline; Barcellos-Hoff, Mary Helen; Yingling, Jonathan M.; Zent, Roy; Arteaga, Carlos L.


    The transforming growth factor-betas (TGF{beta}s) are members of a large superfamily of pleiotropic cytokines that also includes the activins and the bone morphogenetic proteins (BMPs). Members of the TGF{beta} family regulate complex physiological processes such cell proliferation, differentiation, adhesion, cell-cell and cell-matrix interactions, motility, and cell death, among others (Massague, 1998). Dysregulation of TGF{beta} signaling contributes to several pathological processes including cancer, fibrosis, and auto-immune disorders (Massague et al., 2000). The TGF{beta}s elicit their biological effects by binding to type II and type I transmembrane receptor serine-threonine kinases (T{beta}RII and T{beta}RI) which, in turn, phosphorylated Smad 2 and Smad 3. Phosphorylated Smad 2/3 associate with Smad 4 and, as a heteromeric complex, translocate to the nucleus where they regulate gene transcription. The inhibitory Smad7 down regulates TGF{beta} signaling by binding to activated T{beta}RI and interfering with its ability to phosphorylate Smad 2/3 (Derynck and Zhang, 2003; Shi and Massague, 2003). Signaling is also regulated by Smad proteolysis. TGF{beta} receptor-mediated activation results in multi-ubiquitination of Smad 2 in the nucleus and subsequent degradation of Smad 2 by the proteasome (Lo and Massague, 1999). Activation of TGF{beta} receptors also induces mobilization of a Smad 7-Smurf complex from the nucleus to the cytoplasm; this complex recognizes the activated receptors and mediates their ubiquitination and internalization via caveolin-rich vesicles, leading to termination of TGF{beta} signaling (Di Guglielmo et al., 2003). Other signal transducers/pathways have been implicated in TGF{beta} actions. These include the extracellular signal-regulated kinase (Erk), c-Jun N-terminal kinase (Jnk), p38 mitogen-activated protein kinase (MAPK), protein phosphatase PP2A, phosphatidylinositol-3 kinase (PI3K), and the family of Rho GTPases [reviewed in (Derynck and Zhang, 2003)]. Although signaling by Smads has been shown to be causally associated with the anti-proliferative effect of TGF{beta} (Datto et al., 1999; Liu et al., 1997), the role of non-Smad effectors on mediating the cellular effects of TGF{beta} is less well characterized.

  2. Inhibiting prolactin by cabergoline accelerates mammary gland remodeling during the early dry period in dairy cows. (United States)

    Boutinaud, M; Isaka, N; Gandemer, E; Lamberton, P; Wiart, S; Taranilla, A I De Prado; Sordillo, L M; Lollivier, V


    The inhibition of prolactin release using cabergoline, a dopamine agonist, is an effective strategy to accelerate the changes in mammary secretion composition after drying-off. The objective of this study was to determine how cabergoline may affect mammary tissue remodeling during early involution. Holstein dairy cows were treated with either a single i.m. administration of 5.6 mg of cabergoline (Velactis, Ceva Santé Animale, Libourne, France, n = 7) or placebo (n = 7) at the time of drying-off. Mammary biopsy samples were collected 1 wk before drying-off (d -6), after 30 h of milk accumulation (d 1), and again 8 d following drying-off (d 8) to determine changes in gene expression, lactoferrin content, and cell turnover. Blood and mammary secretion samples were collected at d -6 and again at d 1, 2, 3, 4, 8, and 14 following the abrupt cessation of lactation to evaluate indicators of blood-milk barrier integrity and other markers of mammary tissue remodeling. Cabergoline induced less SLC2A1, BAX, CAPN2, and IGFBP5 mRNA expression. In contrast, cabergoline did not modify changes in cell proliferation and apoptosis. Following the cessation of lactation, changes in mammary secretion composition (Na+ and K+) and blood lactose concentrations were indicative of a loss in the blood-milk barrier function in both treatment groups. Cabergoline treatment affected only Na+ and K+ concentrations at d 1, suggesting a moderate increase in tight junction permeability. The increase in the activity of MMP9 and in mammary epithelial cell concentration in mammary secretions was greater in cabergoline-treated cows than in control cows, suggesting more mammary tissue remodeling. The increase in lactoferrin immunostaining in the mammary tissue occurred earlier for cabergoline-treated cows than for control cows, and was essentially localized in the stroma. Changes in some key markers of mammary involution suggest that cabergoline accelerates mammary gland remodeling. Thus, a single

  3. Neutrophils drive accelerated tumor progression in the collagen-dense mammary tumor microenvironment


    Garc?a-Mendoza, Mar?a G.; Inman, David R.; Ponik, Suzanne M.; Jeffery, Justin J; Sheerar, Dagna S.; Van Doorn, Rachel R.; Keely, Patricia J.


    Background High mammographic density has been correlated with a 4-fold to 6-fold increased risk of developing breast cancer, and is associated with increased stromal deposition of extracellular matrix proteins, including collagen I. The molecular and cellular mechanisms responsible for high breast tissue density are not completely understood. Methods We previously described accelerated tumor formation and metastases in a transgenic mouse model of collagen-dense mammary tumors (type I collagen...

  4. Do myoepithelial cells hold the key for breast tumorprogression?

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    Polyak, Kornelia; Hu, Min


    Mammary myoepithelial cells have been the foster child of breast cancer biology and have been largely ignored since they were considered to be less important for tumorigenesis than luminal epithelial cells from which most of breast carcinomas are thought to arise. In recent years as our knowledge in stem cell biology and the cellular microenvironment has been increasing myoepithelial cells are slowly starting to gain more attention. Emerging data raise the hypothesis if myoepithelial cells play a key role in breast tumor progression by regulating the in situ to invasive carcinoma transition and if myoepithelial cells are part of the mammary stem cell niche. Paracrine interactions between myoepithelial and luminal epithelial cells are known to be important for cell cycle arrest, establishing epithelial cell polarity, and inhibiting migration and invasion. Based on these functions normal mammary myoepithelial cells have been called ''natural tumor suppressors''. However, during tumor progression myoepithelial cells seem to loose these properties and eventually they themselves diminish as tumors become invasive. Better understanding of myoepithelial cell function and their role in tumor progression may lead to their exploitation for cancer therapeutic and preventative measures.

  5. Stromal PDGFR-α Activation Enhances Matrix Stiffness, Impedes Mammary Ductal Development, and Accelerates Tumor Growth. (United States)

    Hammer, Anisha M; Sizemore, Gina M; Shukla, Vasudha C; Avendano, Alex; Sizemore, Steven T; Chang, Jonathan J; Kladney, Raleigh D; Cuitiño, Maria C; Thies, Katie A; Verfurth, Quinn; Chakravarti, Arnab; Yee, Lisa D; Leone, Gustavo; Song, Jonathan W; Ghadiali, Samir N; Ostrowski, Michael C


    The extracellular matrix (ECM) is critical for mammary ductal development and differentiation, but how mammary fibroblasts regulate ECM remodeling remains to be elucidated. Herein, we used a mouse genetic model to activate platelet derived growth factor receptor-alpha (PDGFRα) specifically in the stroma. Hyperactivation of PDGFRα in the mammary stroma severely hindered pubertal mammary ductal morphogenesis, but did not interrupt the lobuloalveolar differentiation program. Increased stromal PDGFRα signaling induced mammary fat pad fibrosis with a corresponding increase in interstitial hyaluronic acid (HA) and collagen deposition. Mammary fibroblasts with PDGFRα hyperactivation also decreased hydraulic permeability of a collagen substrate in an in vitro microfluidic device assay, which was mitigated by inhibition of either PDGFRα or HA. Fibrosis seen in this model significantly increased the overall stiffness of the mammary gland as measured by atomic force microscopy. Further, mammary tumor cells injected orthotopically in the fat pads of mice with stromal activation of PDGFRα grew larger tumors compared to controls. Taken together, our data establish that aberrant stromal PDGFRα signaling disrupts ECM homeostasis during mammary gland development, resulting in increased mammary stiffness and increased potential for tumor growth. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Stromal PDGFR-α Activation Enhances Matrix Stiffness, Impedes Mammary Ductal Development, and Accelerates Tumor Growth

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    Anisha M. Hammer


    Full Text Available The extracellular matrix (ECM is critical for mammary ductal development and differentiation, but how mammary fibroblasts regulate ECM remodeling remains to be elucidated. Herein, we used a mouse genetic model to activate platelet derived growth factor receptor-alpha (PDGFRα specifically in the stroma. Hyperactivation of PDGFRα in the mammary stroma severely hindered pubertal mammary ductal morphogenesis, but did not interrupt the lobuloalveolar differentiation program. Increased stromal PDGFRα signaling induced mammary fat pad fibrosis with a corresponding increase in interstitial hyaluronic acid (HA and collagen deposition. Mammary fibroblasts with PDGFRα hyperactivation also decreased hydraulic permeability of a collagen substrate in an in vitro microfluidic device assay, which was mitigated by inhibition of either PDGFRα or HA. Fibrosis seen in this model significantly increased the overall stiffness of the mammary gland as measured by atomic force microscopy. Further, mammary tumor cells injected orthotopically in the fat pads of mice with stromal activation of PDGFRα grew larger tumors compared to controls. Taken together, our data establish that aberrant stromal PDGFRα signaling disrupts ECM homeostasis during mammary gland development, resulting in increased mammary stiffness and increased potential for tumor growth.

  7. Mutant PIK3CA accelerates HER2-driven transgenic mammary tumors and induces resistance to combinations of anti-HER2 therapies (United States)

    Hanker, Ariella B.; Pfefferle, Adam D.; Balko, Justin M.; Kuba, María Gabriela; Young, Christian D.; Sánchez, Violeta; Sutton, Cammie R.; Cheng, Hailing; Perou, Charles M.; Cook, Rebecca S.; Arteaga, Carlos L.


    Human epidermal growth factor receptor 2 (HER2; ERBB2) amplification and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations often co-occur in breast cancer. Aberrant activation of the phosphatidylinositol 3-kinase (PI3K) pathway has been shown to correlate with a diminished response to HER2-directed therapies. We generated a mouse model of HER2-overexpressing (HER2+), PIK3CAH1047R-mutant breast cancer. Mice expressing both human HER2 and mutant PIK3CA in the mammary epithelium developed tumors with shorter latencies compared with mice expressing either oncogene alone. HER2 and mutant PIK3CA also cooperated to promote lung metastases. By microarray analysis, HER2-driven tumors clustered with luminal breast cancers, whereas mutant PIK3CA tumors were associated with claudin-low breast cancers. PIK3CA and HER2+/PIK3CA tumors expressed elevated transcripts encoding markers of epithelial-to-mesenchymal transition and stem cells. Cells from HER2+/PIK3CA tumors more efficiently formed mammospheres and lung metastases. Finally, HER2+/PIK3CA tumors were resistant to trastuzumab alone and in combination with lapatinib or pertuzumab. Both drug resistance and enhanced mammosphere formation were reversed by treatment with a PI3K inhibitor. In sum, PIK3CAH1047R accelerates HER2-mediated breast epithelial transformation and metastatic progression, alters the intrinsic phenotype of HER2-overexpressing cancers, and generates resistance to approved combinations of anti-HER2 therapies. PMID:23940356

  8. Mammary Duct Ectasia (United States)

    ... lumps Mammary duct ectasia Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  9. The role of neutralizing antibodies for mouse mammary tumor virus transmission and mammary cancer development (United States)

    Finke, Daniela; Luther, Sanjiv A.; Acha-Orbea, Hans


    Mouse mammary tumor virus (MMTV) infection establishes chronic germinal centers and a lifelong neutralizing Ab response. We show that removal of the draining lymph node after establishment of the germinal center reaction led to complete loss of neutralizing Abs despite comparable infection levels in peripheral lymphocytes. Importantly, in the absence of neutralization, only the exocrine organs mammary gland, salivary gland, pancreas, and skin showed strikingly increased infection, resulting in accelerated mammary tumor development. Induction of stronger neutralization did not influence chronic infection levels of peripheral lymphoid organs but strongly inhibited mammary gland infection and virus transmission to the next generation. Taken together, we provide evidence that a tight equilibrium in virus neutralization allows limited infection of exocrine organs and controls cancer development in susceptible mouse strains. These experiments show that a strong neutralizing Ab response induced after infection is not able to control lymphoid MMTV infection. Strong neutralization, however, is capable of blocking amplification of mammary gland infection, tumor development, and virus transmission to the next generation. The results also indicate a role of neutralization in natural resistance to MMTV infection.

  10. Immunoglobins in mammary secretions

    DEFF Research Database (Denmark)

    Hurley, W L; Theil, Peter Kappel


    Immunoglobulins secreted in colostrum and milk by the lactating mammal are major factors providing immune protection to the newborn. Immunoglobulins in mammary secretions represent the cumulative immune response of the lactating animal to exposure to antigenic stimulation that occurs through...... interaction with the environment. Extensive species variability exists in how and when maternal immunoglobulins are transferred to the neonate. In addition, there is a range of mechanisms by which the transferred immunoglobulins may play a protective role in the neonate. This chapter reviews...... the immunoglobulins found in mammary secretions in the context of their diversity of structure, origin, mechanisms of transfer, and function....

  11. Mammary gland stem cells

    DEFF Research Database (Denmark)

    Fridriksdottir, Agla J R; Petersen, Ole W; Rønnov-Jessen, Lone


    Distinct subsets of cells, including cells with stem cell-like properties, have been proposed to exist in normal human breast epithelium and breast carcinomas. The cellular origins of epithelial cells contributing to gland development, tissue homeostasis and cancer are, however, still poorly...... and differences between mouse and human gland development with particular emphasis on the identity and localization of stem cells, and the influence of the surrounding microenvironment. It is concluded that while recent advances in the field have contributed immense insight into how the normal mammary gland...... develops and is maintained, significant discrepancies exist between the mouse and human gland which should be taken into consideration in current and future models of mammary stem cell biology....

  12. Humanization of the mouse mammary gland. (United States)

    Wronski, A; Arendt, L M; Kuperwasser, Charlotte


    Although mouse models have provided invaluable information on the mechanisms of mammary gland development, anatomical and developmental differences between human and mice limit full understanding of this fundamental process. Humanization of the mouse mammary gland by injecting immortalized human breast stromal cells into the cleared murine mammary fat pad enables the growth and development of human mammary epithelial cells or tissue. This facilitates the characterization of human mammary gland development or tumorigenesis by utilizing the mouse mammary fat pad. Here we describe the process of isolating human mammary stromal and epithelial cells as well as their introduction into the mammary fat pads of immunocompromised mice.

  13. Bone Morphogenetic Proteins stimulate mammary fibroblasts to promote mammary carcinoma cell invasion.

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    Philip Owens

    Full Text Available Bone Morphogenetic Proteins (BMPs are secreted cytokines that are part of the Transforming Growth Factor β (TGFβ superfamily. BMPs have been shown to be highly expressed in human breast cancers, and loss of BMP signaling in mammary carcinomas has been shown to accelerate metastases. Interestingly, other work has indicated that stimulation of dermal fibroblasts with BMP can enhance secretion of pro-tumorigenic factors. Furthermore, treatment of carcinoma-associated fibroblasts (CAFs derived from a mouse prostate carcinoma with BMP4 was shown to stimulate angiogenesis. We sought to determine the effect of BMP treatment on mammary fibroblasts. A large number of secreted pro-inflammatory cytokines and matrix-metallo proteases (MMPs were found to be upregulated in response to BMP4 treatment. Fibroblasts that were stimulated with BMP4 were found to enhance mammary carcinoma cell invasion, and these effects were inhibited by a BMP receptor kinase antagonist. Treatment with BMP in turn elevated pro-tumorigenic secreted factors such as IL-6 and MMP-3. These experiments demonstrate that BMP may stimulate tumor progression within the tumor microenvironment.

  14. Mammary tuberculosis: percutaneous treatment of a mammary tuberculous abscess

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    Romero, C.; Carreira, C.; Cereceda, C.; Pinto, J. [Servicio de Radiologia, Hospital Virgen de la Salud, Toledo (Spain); Lopez, R.; Bolanos, F. [Servicio de Cirugia, Hospital Virgen de la Salud, Toledo (Spain)


    It is currently very rare to find mammary involvement in cases of tuberculosis, in either primary or secondary form. Diagnosis is classically clinical and microbiological, and the basic techniques used in imaging diagnosis are mammography and ultrasound. Computed tomography may define the involvement of the thoracic wall in those cases which present as mammary masses adhering to deep levels, and is also able to evaluate accompanying pulmonary disease, if it is present. Traditionally, treatment has consisted of quadrantectomy and specific antibiotic therapy. We present a case of tuberculous mammary abscess secondary to pulmonary disease, which was treated by percutaneous drainage controlled by CT and specific antibiotic therapy. We revise the diagnosis, differential diagnosis and treatment of mammary tuberculosis. (orig.)

  15. Mammary Analogue Secretory Carcinoma. (United States)

    Stevens, Todd M; Parekh, Vishwas


    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor that shares the same histologic appearance and ETV6 gene (12p13) rearrangement as secretory carcinoma of the breast. Prior to its recognition, MASC cases were commonly labeled acinic cell carcinoma and adenocarcinoma, not otherwise specified. Despite distinctive histologic features, MASC may be difficult to distinguish from other salivary gland tumors, in particular zymogen-poor acinic cell carcinoma and low-grade salivary duct carcinoma. Although characteristic morphologic and immunohistochemical features form the basis of a diagnosis of MASC, the presence of an ETV6-NTRK3 gene fusion is confirmatory. Given its recent recognition the true prognostic import of MASC is not yet clearly defined.

  16. TBX3 over-expression causes mammary gland hyperplasia and increases mammary stem-like cells in an inducible transgenic mouse model

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    Gulsen Gultekin


    Full Text Available Abstract Background The T-box transcription factor TBX3 is necessary for early embryonic development and for the normal development of the mammary gland. Homozygous mutations, in mice, are embryonic lethal while heterozygous mutations result in perturbed mammary gland development. In humans, mutations that result in the haploinsufficiency of TBX3 causes Ulnar Mammary Syndrome (UMS characterized by mammary gland hypoplasia as well as other congenital defects. In addition to its role in mammary gland development, various studies have also supported a role for Tbx3 in breast cancer development. TBX3 is over-expressed in various breast cancer cell lines as well as cancer tissue and has been found to contribute to breast cancer cell migration. Previous studies have suggested that TBX3 contributes to cancer development by its ability to bypass senescence by repressing the expression of p14ARF-tumor suppressor. Although many studies have shown that a dysregulation of TBX3 expression may contribute to cancer progression, no direct evidence shows TBX3 causes breast cancer. Results In this study, we created doxycycline inducible double transgenic mice (MMTV-rtTA;tet-myc-TBX3-IRES-Luciferase to test whether TBX3 over-expression can induce tumor formation within the mammary gland. Although over-expression of TBX3, alone, did not induce tumor formation it did promote accelerated mammary gland development by increasing mammary epithelial cell proliferation. We also show that TBX3 directly binds to and represses NFκBIB, an inhibitor of the NF-κB pathway known to play a role in regulating cell proliferation. Lastly, we also show that the over-expression of TBX3 is associated with an increase in mammary stem-like cells. Conclusions Overall, our data suggests that over-expression of TBX3 may contribute to breast cancer development by promoting accelerated mammary gland development through the inhibition of the NF-κB pathway and stimulation of both mammary

  17. Canine mammary tumors - clinical survey

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    Elena Atanaskova Petrov


    Full Text Available Mammary tumours are the second most frequent neoplasia in dogs, mainly affecting older female patients. Approximately 50% of the mammary tumours are malignant with high percentage of mortality if not treated in time. The aim of this study was to analyze the data of canine patients with mammary tumours, to evaluate the type of tumours, as well as the relationship between tumour incidence and dogs’ age, reproductive cycle and sterilization. The survey was used to retrieve the information in the period of two years from the patient data base of the University Veterinary Hospital at the Faculty of Veterinary medicine in Skopje. Patients included in this survey were subjected to routine clinical investigation and additional laboratory tests (cytological examination, x-rays imaging, CBC and biochemical profile, histopathology of the tumor samples. Aged female patients (12 – 13 years are the most susceptible category for development of mammary tumours. The reproductive history showed that five of the patients with malignant mammary tumourshave never whelped and were not treated with any exogenous hormones. Malignant tumours (adenocarcinoma were diagnosed in 90% of the patients. Three patients died due to lung metastasis. Late diagnosis is one of the major problems that results in lethal outcome due to lung metastases. Since ovarian steroids play an important role in the aetiology, the most effective prevention of mammary tumoursis elective ovariectomy of the bitch at an early age.

  18. Mammary carcinoma diagnostics and therapy; Diagnostik und Therapie des Mammakarzinoms

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    Fischer, Uwe; Baum, Friedemann (eds.) [Diagnostisches Brustzentrum Goettingen BZG, Goettingen(Germany)


    The book on mammary carcinoma diagnostics and therapy covers the following issues: development, anatomy and physiology of the mammary glands, pathology of benign and malign mammary gland changes, non-imaging diagnostics; mammography; ultrasonic mammography; magnetic resonance tomography of the mammary glands; imaging diagnostics findings; mammary interventions; examination concepts; operative therapy of the mammary carcinoma; chemotherapy of the mammary carcinoma; radio-oncological therapy of the mammary carcinoma; logistics in a medical center for mammary gland diseases; logistics in an interdisciplinary center for mammary diseases; dialogue conduction and psycho-social attendance.

  19. Chronic social isolation is associated with metabolic gene expression changes specific to mammary adipose tissue. (United States)

    Volden, Paul A; Wonder, Erin L; Skor, Maxwell N; Carmean, Christopher M; Patel, Feenalie N; Ye, Honggang; Kocherginsky, Masha; McClintock, Martha K; Brady, Matthew J; Conzen, Suzanne D


    Chronic social isolation is linked to increased mammary tumor growth in rodent models of breast cancer. In the C3(1)/SV40 T-antigen FVB/N (TAg) mouse model of "triple-negative" breast cancer, the heightened stress response elicited by social isolation has been associated with increased expression of metabolic genes in the mammary gland before invasive tumors develop (i.e., during the in situ carcinoma stage). To further understand the mechanisms underlying how accelerated mammary tumor growth is associated with social isolation, we separated the mammary gland adipose tissue from adjacent ductal epithelial cells and analyzed individual cell types for changes in metabolic gene expression. Specifically, increased expression of the key metabolic genes Acaca, Hk2, and Acly was found in the adipocyte, rather than the epithelial fraction. Surprisingly, metabolic gene expression was not significantly increased in visceral adipose depots of socially isolated female mice. As expected, increased metabolic gene expression in the mammary adipocytes of socially isolated mice coincided with increased glucose metabolism, lipid synthesis, and leptin secretion from this adipose depot. Furthermore, application of media that had been cultured with isolated mouse mammary adipose tissue (conditioned media) resulted in increased proliferation of mammary cancer cells relative to group-housed-conditioned media. These results suggest that exposure to a chronic stressor (social isolation) results in specific metabolic reprogramming in mammary gland adipocytes that in turn contributes to increased proliferation of adjacent preinvasive malignant epithelial cells. Metabolites and/or tumor growth-promoting proteins secreted from adipose tissue could identify biomarkers and/or targets for preventive intervention in breast cancer. ©2013 AACR.

  20. Chronic social isolation is associated with metabolic gene expression changes specific to mammary adipose tissue (United States)

    Volden, Paul A.; Wonder, Erin L.; Skor, Maxwell N.; Carmean, Christopher M.; Patel, Feenalie N.; Ye, Honggang; Kocherginsky, Masha; McClintock, Martha K.; Brady, Matthew J.; Conzen, Suzanne D.


    Chronic social isolation is linked to increased mammary tumor growth in rodent models of breast cancer. In the C3(1)/SV40 T-antigen FVB/N (TAg) mouse model of “triple-negative” breast cancer, the heightened stress response elicited by social isolation has been associated with increased expression of metabolic genes in the mammary gland before invasive tumors develop (i.e. during the in situ carcinoma stage). To further understand the mechanisms underlying how accelerated mammary tumor growth is associated with social isolation, we separated the mammary gland adipose tissue from adjacent ductal epithelial cells and analyzed individual cell types for changes in metabolic gene expression. Specifically, increased expression of the key metabolic genes Acaca, Hk2 and Acly was found in the adipocyte, rather than the epithelial fraction. Surprisingly, metabolic gene expression was not significantly increased in visceral adipose depots of socially isolated female mice. As expected, increased metabolic gene expression in the mammary adipocytes of socially isolated mice coincided with increased glucose metabolism, lipid synthesis, and leptin secretion from this adipose depot. Furthermore, application of media that had been cultured with isolated mouse mammary adipose tissue (conditioned media) resulted in increased proliferation of mammary cancer cells relative to group-housed conditioned media. These results suggest that exposure to a chronic stressor (social isolation) results in specific metabolic reprogramming in mammary gland adipocytes that in turn contributes to increased proliferation of adjacent pre-invasive malignant epithelial cells. Metabolites and/or tumor growth-promoting proteins secreted from adipose tissue could identify biomarkers and/or targets for preventive intervention in breast cancer. PMID:23780289

  1. Mammary Gland Evaluation in Juvenile Toxicity Studies: Temporal Developmental Patterns in the Male and Female Harlan Sprague Dawley Rat (United States)

    Filgo, Adam J.; Foley, Julie F.; Puvanesarajah, Samantha; Borde, Aditi R.; Midkiff, Bentley R.; Reed, Casey E.; Chappell, Vesna A.; Alexander, Lydia B.; Borde, Pretish R.; Troester, Melissa A.; Hayes Bouknight, Schantel A.; Fenton, Suzanne E.


    There are currently no reports describing mammary gland development in the Harlan Sprague Dawley (HSD) rat, the current strain of choice for National Toxicology Program (NTP) testing. Our goals were to empower the NTP, contract labs and other researchers in understanding and interpretation of chemical effects in this rat strain. To delineate similarities/differences between the female and male mammary gland, data were compiled starting on embryonic day 15.5 through postnatal day 70. Mammary gland whole mounts, histology sections, and immunohistochemically-stained tissues for estrogen, progesterone and androgen receptors were evaluated in both sexes; qualitative and quantitative differences are highlighted using a comprehensive visual timeline. Research on endocrine disrupting chemicals in animal models has highlighted chemically-induced mammary gland anomalies which may potentially impact human health. In order to investigate these effects within the HSD strain, 2,3,7,8-tetrachlorodibenzo p-dioxin, diethylstilbestrol or vehicle control was gavage dosed on gestation day 15 and 18 to demonstrate delayed, accelerated and control mammary gland growth in offspring, respectively. We provide illustrations of normal and chemically altered mammary gland development in HSD male and female rats to help inform researchers unfamiliar with the tissue and may facilitate enhanced evaluation of both male and female mammary glands in juvenile toxicity studies. PMID:27613106

  2. Ectopic mammary tissue in vulva

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    Đorđević Momčilo


    Full Text Available Background. Ectopic mammary gland tissue is a residual tissue that persists during the embryologic development along ectodermal primitive milk streaks. Incomplete involution anywhere along the primitive milk streak can result in accessory or ectopic mammary tissue. Case report. A woman, 27-year old, admitted to Obstetrics and Gynecology Clinic Kragujevac for surgery, of goose-egg size, vulva tumor, of elastic consistency. Menarche started in 12 years of age, with the regular menstrual cycle, without previous gynecological diseases. The woman had one pregnancy terminated by cesarean section because of the multiple (twin pregnancy. Excision of the tumor was completely done in the total endotracheal anesthesia. Pathohistologic (PH findings was: Dysplasia fibrosa cystica simplex mammae, with focuses of sclerosing adenosis. Expression of estrogen (ER and progesterone receptors (PR were positive. Conclusion. Ectopic mammary tissue in vulva in adult period is very rarely seen, and can be changed pathologically as well as normally positioned breast tissue into benign cystic changes, benign tumors, adenomas and fibroadenomas and tumors. Cells with low ER/PR receptor level grow independently of estrogene stimulation and they could be resistant to hormonal therapy effects.

  3. Effects of maternal dietary exposure to cadmium during pregnancy on mammary cancer risk among female offspring

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    Jennifer Davis


    Full Text Available Background: Since heavy metal cadmium is an endocrine disrupting chemical, we investigated whether maternal exposure to cadmium during the pregnancy alters mammary tumorigenesis among female offspring. Methods: From gestation day 10 to day 19, pregnant rat dams were fed modified American Institute of Nutrition (AIN93G diet containing 39% energy from fat (baseline diet, or the baseline diet containing moderate (75 μg/kg of feed or high (150 μg/kg cadmium levels. Some dams were injected with 10 μg 17β-estradiol (E2 daily between gestation days 10 and 19. Results: Rats exposed to a moderate cadmium dose in utero were heavier and exhibited accelerated puberty onset. Both moderate and high cadmium dose led to increased circulating testosterone levels and reduced the expression of androgen receptor in the mammary gland. The moderate cadmium dose mimicked the effects of in utero E2 exposure on mammary gland morphology and increased both the number of terminal end buds and pre-malignant hyperplastic alveolar nodules (HANs, but in contrast to the E2, it did not increase 7, 12-dimethylbenz (a anthracene-induced mammary tumorigenesis. Conclusions: The effects of in utero cadmium exposure were dependent on the dose given to pregnant dams: Moderate, but not high, cadmium dose mimicked some of the effects seen in the in utero E2 exposed rats, such as increased HANs in the mammary gland.

  4. STAT5 deletion in macrophages alters ductal elongation and branching during mammary gland development. (United States)

    Brady, Nicholas J; Farrar, Michael A; Schwertfeger, Kathryn L


    Macrophages are required for proper mammary gland development and maintaining tissue homeostasis. However, the mechanisms by which macrophages regulate this process remain unclear. Here, we identify STAT5 as an important regulator of macrophage function in the developing mammary gland. Analysis of mammary glands from mice with STAT5-deficient macrophages demonstrates delayed ductal elongation, enhanced ductal branching and increased epithelial proliferation. Further analysis reveals that STAT5 deletion in macrophages leads to enhanced expression of proliferative factors such as Cyp19a1/aromatase and IL-6. Mechanistic studies demonstrate that STAT5 binds directly to the Cyp19a1 promoter in macrophages to suppress gene expression and that loss of STAT5 results in enhanced stromal expression of aromatase. Finally, we demonstrate that STAT5 deletion in macrophages cooperates with oncogenic initiation in mammary epithelium to accelerate the formation of estrogen receptor (ER)-positive hyperplasias. These studies establish the importance of STAT5 in macrophages during ductal morphogenesis in the mammary gland and demonstrate that altering STAT5 function in macrophages can affect the development of tissue-specific disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Mammary Hypertrophy in an Ovariohysterectomized Cat


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


    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.

  6. escherichia coli serotypes confirmed in experimental mammary ...

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    SEROTYPES CONFIRMED IN EXPERIMENTAL MAMMARY GLAND. INFECTIONS. P. A. AKPAN AND ... 037, 02a and 109) in mammary glands of experimental cows (cow 105, 107 and 102 respectively). Pathogenicity of the E. coli which ..... Akpan, P. A and Ikpeme, E. U., 2005. pathology of. Experimental Escherichia Coli ...

  7. Evolution of somatic mutations in mammary tumors in transgenic mice is influenced by the inherited genotype

    Directory of Open Access Journals (Sweden)

    Li Yi


    Full Text Available Abstract Background MMTV-Wnt1 transgenic mice develop mammary hyperplasia early in development, followed by the appearance of solitary mammary tumors with a high proportion of cells expressing early lineage markers and many myoepithelial cells. The occurrence of tumors is accelerated in experiments that activate FGF proto-oncogenes or remove the tumor suppressor genes Pten or P53, implying that secondary oncogenic events are required for progression from mammary hyperplasia to carcinoma. It is not known, however, which oncogenic pathways contribute to Wnt1-induced tumorigenesis – further experimental manipulation of these mice is needed. Secondary events also appear to be required for mammary tumorigenesis in MMTV-Neu transgenic mice because the transgene in the tumors usually contains an acquired mutation that activates the Neu protein-tyrosine kinase. Methods cDNA or DNA from the mammary glands and mammary tumors from MMTV-Wnt1, MMTV-Wnt1/p53-/-, MMTV-Neu transgenic mice, and newly generated MMTV-Wnt1/MMTV-Neu bitransgenic mice, was sequenced to seek activating mutations in H-Ras, K-Ras, and N-Ras genes, or in the MMTV-Neu transgene. In addition, tumors from bitransgenic animals were examined to determine the cellular phenotype. Results We found activating mutations at codons 12, 13, and 61 of H-Ras in just over half of the mammary tumors in MMTV-Wnt1 transgenic mice, and we confirmed the high frequency of activating mutations of Neu in tumors in MMTV-Neu transgenic mice. Tumors appeared earlier in bitransgenic MMTV-Wnt1/MMTV-Neu mice, but no Ras or MMTV-Neu mutations were found in these tumors, which were phenotypically similar to those arising in MMTV-Wnt1 mice. In addition, no Ras mutations were found in the mammary tumors that arise in MMTV-Wnt1 transgenic mice lacking an intact P53 gene. Conclusions Tumorigenic properties of cells undergoing functionally significant secondary mutations in H-Ras or the MMTV-Neu transgene allow selection

  8. Loss of Igfbp7 Causes Precocious Involution in Lactating Mouse Mammary Gland (United States)

    Chatterjee, Sumanta; Bacopulos, Stephanie; Yang, Wenyi; Amemiya, Yutaka; Spyropoulos, Demetri


    Background Insulin like growth factors (IGFs) and their binding proteins (IGFBPs) are secreted peptides that play major roles in regulating the normal development and maturation of mammary gland. While Igfbp7 has been shown to decrease breast tumor growth, its role in regulating the normal mammary gland development has not been studied. To this end, we generated Igfbp7-null mice and examined the development and maturation of mammary glands in the virgin, pregnant and lactating animals. Results We report here that loss of Igfbp7 significantly retards mammary gland development in the virgin animals. More significantly, the pregnant Igfpb7-null glands contained fewer alveolar structures and that during lactation these glands exhibit the morphological changes that are associated with involution. The transcriptome profile of the Igfbp7-null glands on the lactation day 3 revealed a distinct involution-related gene signature compared to the lactating WT glands. Interestingly, we found that the lactating Igfbp7-null glands exhibit increased expression of Stat3 and enhanced activation of (phosphorylated) Stat3, combined with decreased expression of Stat5 suggesting that the absence of Igfbp7 accelerates the onset of involution. We also found that in absence of Igfpb7, the lactating glands contain increased Igfbp5 protein along with decreased expression of IGF-1 Receptor and Akt activation. Finally, we show that during the normal course of involution, Igfbp7 expression is significantly decreased in the mammary gland. Conclusion Our data suggest that loss of Igfbp7 induces precocious involution possibly through diminished cell survival signals. Our findings identify Igfbp7 as major regulator of involution in the mammary gland. PMID:24505323

  9. Metastatic mammary carcinoma in a cow

    Directory of Open Access Journals (Sweden)

    Manoela Marchezan Piva

    Full Text Available ABSTRACT: Mammary gland neoplasms in cattle are rarely observed in the field veterinary diagnostics routine. Therefore, the objective of this study is to report a metastatic mammary carcinoma in a fourteen-year-old Holstein cow in the state of Santa Catarina, Brazil. The animal was diagnosed by the field veterinarian with clinical mastitis that was unresponsive to treatment, and was euthanized due to the poor prognosis. At the necropsy, multiple yellow, firm, and sometimes friable nodules, ranging from 0.1 to 20cm were observed in all mammary glands, lymph nodes, kidneys, spleen, liver, pancreas, mediastinal lymph nodes, heart, and lungs. The final diagnosis of mammary carcinoma was established through the association of clinical, necropsy, histopathological, and immunohistochemical findings. Differential diagnoses included diseases such as bovine tuberculosis and chronic fungal or bacterial mastitis.

  10. Selenium in human mammary carcinogenesis

    DEFF Research Database (Denmark)

    Overvad, Kim; Grøn, P.; Langhoff, Otto


    In a case-referent study on the possible role of selenium in human mammary carcinogenesis, serum selenium was found to be 79 +/- 12 micrograms/l in 66 cases and 81 +/- 12 micrograms/l in 93 referents. An internal trend in serum selenium was observed among cases (TNM stage I 81 +/- 11 micrograms....../l and TNM stage II 76 +/- 13 micrograms selenium/l), indicating disease-mediated changes. The evaluation of selenium as a risk indicator in human breast cancer was therefore restricted to TNM stage I patients (n = 36). Multiple logistic regression analyses including variables associated with selenium levels...... revealed no association between selenium levels and breast cancer risk....

  11. Polarized dermoscopy of mammary Paget disease* (United States)

    de Crignis, Giselly Silva Neto; de Abreu, Luciana; Buçard, Alice Mota; Barcaui, Carlos Baptista


    Mammary Paget's disease is a rare intraepithelial adenocarcinoma, located on the nipple/areola complex, highly associated with breast cancer. Although the international literature emphasizes the dermatoscopic pattern of mammary Paget's disease pigmented variant, the authors describe the dermoscopic findings of classical Paget's disease and demonstrate the presence of chrysalis-like structures, criteria recently described in the literature and not yet reported in Paget's disease. PMID:23739693

  12. Mammary Cancer and Activation of Transposable Elements (United States)


    retrotransposon expression is a later event, and unlikely to play a direct role in cancer ontogeny. 15. SUBJECT TERMS Breast cancer , epigenetic, DNA...transcriptionally activated during pregnancy and lactation, and the mice are predisposed to develop mammary cancer after a minimum of 3 pregnancies and... pregnancy and lactation. After 3 pregnancies and lactations, but not after 1 pregnancy and lactation, females develop mammary cancers at an average

  13. Mammary Adipose Tissue-Derived Lysophospholipids Promote Estrogen Receptor-Negative Mammary Epithelial Cell Proliferation. (United States)

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


    Lysophosphatidic acid (LPA), acting in an autocrine or paracrine fashion through G protein-coupled receptors, has been implicated in many physiologic and pathologic processes, including cancer. LPA is converted from 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 levels. 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 murine 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. Cancer Prev Res; 9(5); 367-78. ©2016 AACR. ©2016 American Association for Cancer Research.

  14. Mammary blood flow and cardiac output during initiated involution of the mammary gland in the rabbit. (United States)

    Jones, C S; Parker, D S


    1. Cardiac output and its distribution to the mammary gland, kidneys, heart, liver and gastrointestinal tract were measured in conscious rabbits at day 1, day 3 and day 6 after removal of the young at day 0. 2. There was no change in cardiac output, proportion of cardiac output delivered to the mammary gland or mammary blood flow 24 hr after the last suckling period. After a further 48 hr there was a significant reduction in the cardiac output, proportion of the cardiac output and blood flow to the mammary gland compared to the values measured in lactating animals. 3. There was no significant difference in blood flow to the other organs although there were changes in the proportion of the cardiac output delivered to the heart, kidney and liver during this period. 4. The change in uptake of glucose, acetate, non-esterified fatty acids and triacylglycerols by the mammary gland are discussed in relation to the reabsorption of milk components.

  15. Scribble modulates the MAPK/Fra1 pathway to disrupt luminal and ductal integrity and suppress tumour formation in the mammary gland.

    Directory of Open Access Journals (Sweden)

    Nathan J Godde


    Full Text Available 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.

  16. Positional Variations in Mammary Gland Development and Cancer


    Veltmaat, Jacqueline M.; Ramsdell, Ann F.; Sterneck, Esta


    Most mammals develop their mammary glands in pairs of which the two counterparts are symmetrically displaced away from the ventral midline. Based on this symmetry and the same functional outcome as a milk-producing organ, the mammary glands are easily presumed to be mere copies of one another. Based on our analysis of published data with inclusion of new results related to mammary development and pathology in mice, we argue that this presumption is incorrect: Between and within pairs, mammary...

  17. Mammary gland stem cells: More puzzles than explanations

    Indian Academy of Sciences (India)

    Mammary gland stem cells (MaSC) have not been identified in spite of extensive research spanning over several decades. This has been primarily due to the complexity of mammary gland structure and its development, cell heterogeneity in the mammary gland and the insufficient knowledge about MaSC markers.

  18. Gynecomastia and mammary gland adenocarcinoma in a Nubian buck. (United States)

    Wooldridge, A A; Gill, M S; Lemarchand, T; Eilts, B; Taylor, H W; Otterson, T


    A 6-year-old Nubian buck was presented for bilateral mammary gland enlargement. Gynecomastia and mastitis were diagnosed, and bilateral mastectomy was performed. Histological examination showed mammary adenocarcinoma, active lactation, hyperplasia, and abscessation. Karyotyping showed a normal male. Clinical, therapeutic, etiologic, and epidemiologic aspects of gynecomastia and mammary gland adenocarcinoma are discussed.

  19. Gynecomastia and mammary gland adenocarcinoma in a Nubian buck.


    Wooldridge, A A; Gill, M S; Lemarchand, T; Eilts, B; Taylor, H. W.; Otterson, T


    A 6-year-old Nubian buck was presented for bilateral mammary gland enlargement. Gynecomastia and mastitis were diagnosed, and bilateral mastectomy was performed. Histological examination showed mammary adenocarcinoma, active lactation, hyperplasia, and abscessation. Karyotyping showed a normal male. Clinical, therapeutic, etiologic, and epidemiologic aspects of gynecomastia and mammary gland adenocarcinoma are discussed.

  20. Mammary fibroadenomatoid hyperplasia in a heifer

    Directory of Open Access Journals (Sweden)

    Lorena Ferreira Silva

    Full Text Available ABSTRACT: This manuscript described the anatomopathological and immunohistochemical findings in a rare case of mammary fibroadenomatoid hyperplasia in a 12-month-old Holstein heifer. A yellow, multilobulated, firm 20cm x 9cm x 6.5cm mass affecting the right quarters of the udder was observed. Total mastectomy was performed. Microscopic evaluation revealed severe hyperplasia of the mammary epithelium and numerous well-differentiated and mildly pleomorphic acini. Additionally, moderate proliferation of the fibrous connective tissue and the myoepithelial cells near the proliferating acini was evident. About 50% of the proliferating epithelial cells showed positive nuclear labeling for estrogen and progesterone receptors, and approximately one-third were positive for Ki-67. In addition, the myoepithelial cells exhibited diffuse nuclear immunoreactivity for p63. Based on the clinical, morphologic, and immunohistochemical findings, a diagnosis of mammary fibroadenomatoid hyperplasia with probable influence of ovarian steroids was made.

  1. Of Microenvironments and Mammary Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    LaBarge, Mark A; Petersen, Ole W; Bissell, Mina J


    In most adult tissues there reside pools of stem and progenitor cells inside specialized microenvironments referred to as niches. The niche protects the stem cells from inappropriate expansion and directs their critical functions. Thus guided, stem cells are able to maintain tissue homeostasis throughout the ebb and flow of metabolic and physical demands encountered over a lifetime. Indeed, a pool of stem cells maintains mammary gland structure throughout development, and responds to the physiological demands associated with pregnancy. This review discusses how stem cells were identified in both human and mouse mammary glands; each requiring different techniques that were determined by differing biological needs and ethical constraints. These studies together create a robust portrait of mammary gland biology and identify the location of the stem cell niche, elucidate a developmental hierarchy, and suggest how the niche might be manipulated for therapeutic benefit.

  2. Mammary tumorigenesis by radiation and its prevention

    Energy Technology Data Exchange (ETDEWEB)

    Onoda, Makoto; Suzuki, Keiko; Inano, Hiroshi [National Inst. of Radiological Sciences, Chiba (Japan)


    Since the breast cancer in women emerged as an important risk associated with exposure to ionizing radiation, we have investigated to clarify the relationship between the induction of mammary tumors by irradiation and the developmental stage of the mammary glands that regulated by the action of endocrine hormones. Besides the radiation, epidemiological studies showed that the process of biosynthesis/metabolism of steroid hormones and hyperlipidemia may be associated with an increased risk of mammary carcinogenesis. In this context, we have undertaken investigations to evaluate the anti-carcinogenic activities of dehydroepiandrosterone (DHEA), a major secretory steroid of the adrenal glands, bezafibrate (BEZF), an anti-hyperlipidemic drug derived from clofibrate, and simvastatin (SIMV), a prodrug of a specific inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, against diethylstilbestrol (DES)-dependent promotion/progression of rat mammary tumors initiated by {gamma}-rays. Pregnant Wistar-MS rats received whole-body irradiation with 2.6 Gy of {gamma}-rays from a {sup 60}Co source at day-20 of pregnancy. The mother rats were fed a diet containing either 0.6% DHEA, 0.15% BEZF or 0.03% SIMV beginning immediately after weaning. They were then implanted subcutaneously with a pellet of DES (3 mg/pellet) in the interscapular area 30 days after termination of nursing and were observed for 1 year for detection of palpable mammary tumors starting from the time of pellet implantation. The administration of dietary DHEA, BEZF or SIMV together with DES implantation in rats irradiated in late pregnancy significantly decreased the total incidence of mammary tumors to 35%, 27% and 36%, respectively, for the 1 year period, while higher tumor incidence (96%, 90% and 88%) was observed in rats fed controldiet. However, neither the number of mammary tumors per tumor-bearing rat nor the latency period in the drug treated groups was different from that observed in the control group

  3. Stromal Effects on Mammary Gland Development and Breast Cancer (United States)

    Wiseman, Bryony S.; Werb, Zena


    Breast cancer manifests itself in the mammary epithelium, yet there is a growing recognition that mammary stromal cells also play an important role in tumorigenesis. During its developmental cycle, the mammary gland displays many of the properties associated with breast cancer, and many of the stromal factors necessary for mammary development also promote or protect against breast cancer. Here we review our present knowledge of the specific factors and cell types that contribute to epithelial-stromal crosstalk during mammary development. To find cures for diseases like breast cancer that rely on epithelial-stromal crosstalk, we must understand how these different cell types communicate with each other.

  4. Tubulopapillary mammary carcinoma in a brown bear (Ursus arctos). (United States)

    Nak, Deniz; Cangul, I Taci; Nak, Yavuz; Cihan, Huseyin; Celimli, Nureddin


    A 28-yr-old, nulliparous female brown bear (Ursus arctos) at the Karacabey Ovakurusu Bear Sanctuary presented with an enlargement of the mammary gland. Three other nodules were also noted in the proximity of the mammary gland and over the vulva. Clinical, hematologic, ultrasonographic, and radiologic examinations were performed; the enlarged mammary gland was removed and the other masses were also excised. Histopathologic examination revealed tubulopapillary carcinoma of the mammary gland, and the other masses were diagnosed as epidermoid cysts. This is the first reported case of tubulopapillary mammary carcinoma accompanied by epidermoid cysts in a bear.

  5. STAT5A Regulates the Survival of Mammary Epithelial Cells and the Development of Mammary Cancer

    National Research Council Canada - National Science Library

    Humphreys, Robin


    The in vivo relationship between epidermal growth factor (EGF) and prolactin/Jak/Stat signaling pathways in mammary gland development and tumorigenesis was explored in transgenic nice overexpressing the TGF alpha gene (TGFalphaTG...

  6. The role of neutralizing antibodies for mouse mammary tumor virus transmission and mammary cancer development


    Finke, Daniela; Luther, Sanjiv A.; Acha-Orbea, Hans


    Mouse mammary tumor virus (MMTV) infection establishes chronic germinal centers and a lifelong neutralizing Ab response. We show that removal of the draining lymph node after establishment of the germinal center reaction led to complete loss of neutralizing Abs despite comparable infection levels in peripheral lymphocytes. Importantly, in the absence of neutralization, only the exocrine organs mammary gland, salivary gland, pancreas, and skin showed strikingly increased infection, resulting i...



    Yu. E. Lyah; V. G. Guryanov; E. A. Yakobson


    Thermography may enable early detection of a cancer tumour within a mammary gland at an early, treatable stage of the illness, but thermogram analysis methods must be developed to achieve this goal. This study analyses the feasibility of applying the Hurst exponent readings algorithm for evaluation of the high dimensionality fractals to reveal any possible difference between normal thermograms (NT) and malignant thermograms (MT).

  8. Future accelerators (?)

    Energy Technology Data Exchange (ETDEWEB)

    John Womersley


    I describe the future accelerator facilities that are currently foreseen for electroweak scale physics, neutrino physics, and nuclear structure. I will explore the physics justification for these machines, and suggest how the case for future accelerators can be made.

  9. Mammary-Stem-Cell-Based Somatic Mouse Models Reveal Breast Cancer Drivers Causing Cell Fate Dysregulation

    Directory of Open Access Journals (Sweden)

    Zheng Zhang


    Full Text Available Cancer genomics has provided an unprecedented opportunity for understanding genetic causes of human cancer. However, distinguishing which mutations are functionally relevant to cancer pathogenesis remains a major challenge. We describe here a mammary stem cell (MaSC organoid-based approach for rapid generation of somatic genetically engineered mouse models (GEMMs. By using RNAi and CRISPR-mediated genome engineering in MaSC-GEMMs, we have discovered that inactivation of Ptpn22 or Mll3, two genes mutated in human breast cancer, greatly accelerated PI3K-driven mammary tumorigenesis. Using these tumor models, we have also identified genetic alterations promoting tumor metastasis and causing resistance to PI3K-targeted therapy. Both Ptpn22 and Mll3 inactivation resulted in disruption of mammary gland differentiation and an increase in stem cell activity. Mechanistically, Mll3 deletion enhanced stem cell activity through activation of the HIF pathway. Thus, our study has established a robust in vivo platform for functional cancer genomics and has discovered functional breast cancer mutations.

  10. Squamous Cell Carcinoma of Mammary Gland in Domestic Cat


    Filgueira,Kilder Dantas; Reche Junior,Archivaldo


    Background: In the feline species, 80% to 93% of neoplasias in the mammary gland are malignant, being the majority carcinomas. Among them, there is the mammary squamous cell carcinoma, which amounts to a very rare neoplasm in the domestic cat, with considerable potential for malignancy. This study aimed to report a case of squamous cell mammary carcinoma in the feline species. Case: A female cat, mixed breed, ten years old, presented history of skin lesion. The cat had been spayed two years b...

  11. Targeting the Prometastatic Microenvironment of the Involuting mammary gland (United States)


    AWARD NUMBER: W81XWH-13-1-0290 TITLE: Targeting the Prometastatic Microenvironment of the Involuting Mammary Gland PRINCIPAL INVESTIGATOR...2016 4. TITLE AND SUBTITLE Targeting the Prometastatic Microenvironment of the Involuting mammary gland 5a. CONTRACT NUMBER Mammary Gland 5b. GRANT...complete) Task 3) Determine the pathological significance of gain and loss of LTBP1 in genetically engineered mouse models. (75% complete) Ø

  12. Electrostatic accelerators


    Hinterberger, F.


    The principle of electrostatic accelerators is presented. We consider Cockcroft– Walton, Van de Graaff and Tandem Van de Graaff accelerators. We resume high voltage generators such as cascade generators, Van de Graaff band generators, Pelletron generators, Laddertron generators and Dynamitron generators. The speci c features of accelerating tubes, ion optics and methods of voltage stabilization are described. We discuss the characteristic beam properties and the variety of possible beams. We ...


    Directory of Open Access Journals (Sweden)

    Yu. E. Lyah


    Full Text Available Thermography may enable early detection of a cancer tumour within a mammary gland at an early, treatable stage of the illness, but thermogram analysis methods must be developed to achieve this goal. This study analyses the feasibility of applying the Hurst exponent readings algorithm for evaluation of the high dimensionality fractals to reveal any possible difference between normal thermograms (NT and malignant thermograms (MT.

  14. Ultrasound appearance of chronic mammary duct ectasia

    Energy Technology Data Exchange (ETDEWEB)

    Duchesne, N. [Ottawa Hospital, Dept. of Radiology, Ottawa, Ontario (Canada)]. E-mail:; Skolnik, S. [Univ. of Toronto, Dept. of Family Medicine, Toronto, Ontario (Canada); Bilmer, S. [Ottawa Hospital, Dept. of Radiology, Ottawa, Ontario (Canada)


    Mammary duct ectasia (MDE), also called periductal mastitis, mammary dysplasia, or plasma cell mastitis, is a benign condition of the mammary gland first described by Haagensen in 1951. The etiology of MDE is unknown and its pathogenesis still controversial; the periductal inflammation could be either the cause or the result of dilated damaged ducts. The process is usually bilateral and asymptomatic, with only a small percentage of patients presenting with symptoms that may include long course of tumour formation, usually subareolar breast lumps, nipple discharge, nipple retraction, mastalgia, and mammary abscess or fistulas. Mammographic presentation of MDE is well known; its features include periductal calcification, benign intraductal calcification, and retroareolar duct dilatation. The periductal calcification results from dystrophic calcification and forms calcified rings or very dense, oval, elongated calcifications, each with a central lucency representing the dilated duct. Intraductal calcifications of duct ectasia represent inspissated intraductal material and are typically of uniform high density, often needle-like, and occasionally branching. Occasionally, there are no mammographic findings, and the diagnosis must rely on sonographic features. Appearance of MDE on ultrasonography (US) depends on the stage of the disease and the contents of the dilated ducts. The acute presentation has been demonstrated in the literature more often than has its chronic counterpart. In the former, duct content can vary from anechoic to isoechoic with surrounding fatty tissue. In chronic MDE, episodes of inflammation are longer. This tends to result in secretions that have a more solid, cheesy texture, partly due to cholesterol crystals, foam cells, and inflammatory cells. For both types of MDE, the appearance can mimic high-grade ductal carcinoma in situ (DCIS) on US. In this essay, 2 chronic MDE cases are presented and their US appearance discussed. Our goal is to explore

  15. Mammary Analogue Secretory Carcinoma Mimicking Salivary Adenoma


    Williams, Lindsay; Chiosea, Simion I.


    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor characterized by ETV6 translocation. It appears that prior studies have identified MASC by reviewing salivary gland carcinomas, such as acinic cell carcinoma and adenocarcinoma, not otherwise specified. To address the possibility of MASC mimicking benign salivary neoplasms we reviewed 12 salivary gland (cyst)adenomas diagnosed prior to the discovery of MASC. One encapsulated (cyst)adenoma of the parotid g...

  16. Electrostatic accelerators

    CERN Document Server

    Hinterberger, F


    The principle of electrostatic accelerators is presented. We consider Cockcroft– Walton, Van de Graaff and Tandem Van de Graaff accelerators. We resume high voltage generators such as cascade generators, Van de Graaff band generators, Pelletron generators, Laddertron generators and Dynamitron generators. The speci c features of accelerating tubes, ion optics and methods of voltage stabilization are described. We discuss the characteristic beam properties and the variety of possible beams. We sketch possible applications and the progress in the development of electrostatic accelerators.

  17. Oxytocin binding sites in bovine mammary tissue

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Xin.


    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)-vasopressin 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.

  18. Accelerating Value Creation with Accelerators

    DEFF Research Database (Denmark)

    Jonsson, Eythor Ivar


    accelerator programs. Microsoft runs accelerators in seven different countries. Accelerators have grown out of the infancy stage and are now an accepted approach to develop new ventures based on cutting-edge technology like the internet of things, mobile technology, big data and virtual reality. It is also...... an approach to facilitate implementation and realization of business ideas and is a lucrative approach to transform research into ventures and to revitalize regions and industries in transition. Investors have noticed that the accelerator approach is a way to increase the possibility of success by funnelling...... with the traditional audit and legal universes and industries are examples of emerging potentials both from a research and business point of view to exploit and explore further. The accelerator approach may therefore be an Idea Watch to consider, no matter which industry you are in, because in essence accelerators...

  19. New insights into lineage restriction of mammary gland epithelium using parity-identified mammary epithelial cells. (United States)

    Chang, Ted H-T; Kunasegaran, Kamini; Tarulli, Gerard A; De Silva, Duvini; Voorhoeve, P Mathijs; Pietersen, Alexandra M


    Parity-identified mammary epithelial cells (PI-MECs) are an interesting cellular subset because they survive involution and are a presumptive target for transformation by human epidermal growth factor receptor 2 (HER2)/neu in mammary tumors. Depending on the type of assay, PI-MECs have been designated lobule-restricted progenitors or multipotent stem/progenitor cells. PI-MECs were reported to be part of the basal population of mammary epithelium based on flow cytometry. We investigated the cellular identity and lineage potential of PI-MECs in intact mammary glands. We performed a quantitative and qualitative analysis of the contribution of PI-MECs to mammary epithelial cell lineages in pregnant and involuted mammary glands by immunohistochemistry, fluorescence-activated cells sorting (FACS), and quantitative polymerase chain reaction. PI-MECs were labeled by the activation of Whey Acidic Protein (WAP)-Cre during pregnancy that results in permanent expression of yellow fluorescent protein. After involution, PI-MECs are present exclusively in the luminal layer of mammary ducts. During pregnancy, PI-MECs contribute to the luminal layer but not the basal layer of alveolar lobules. Strikingly, whereas all luminal estrogen receptor (ER)-negative cells in an alveolus can be derived from PI-MECs, the alveolar ER-positive cells are unlabeled and reminiscent of Notch2-traced L cells. Notably, we observed a significant population of unlabeled alveolar progenitors that resemble PI-MECs based on transcriptional and histological analysis. Our demonstration that PI-MECs are luminal cells underscores that not only basal cells display multi-lineage potential in transplantation assays. However, the lineage potential of PI-MECs in unperturbed mammary glands is remarkably restricted to luminal ER-negative cells of the secretory alveolar lineage. The identification of an unlabeled but functionally similar population of luminal alveolar progenitor cells raises the question of whether PI

  20. Technical note: Mammary gland ultrasonography to evaluate mammary parenchymal composition in prepubertal heifers. (United States)

    Albino, R L; Guimarães, S E F; Daniels, K M; Fontes, M M S; Machado, A F; Dos Santos, G B; Marcondes, M I


    Bovine mammary gland development studies are often terminal or involve invasive biopsy procedures. Therefore, noninvasive means of assessing mammary development should be considered as alternative methods in live animals. The objective was to test if mammary ultrasonography can be used as a noninvasive way to estimate mammary parenchyma (PAR) composition in prepubertal dairy heifers with different average daily body weight gains. In the 84 d preceding, the ultrasound exam heifers were maintained in 1 of 3 treatment groups. Individual heifers were fed a high gain (1 kg/d; n = 6), low gain (0.5 kg/d, n = 6), or maintenance (n = 6) treatment diet. To achieve desired body weight gains, heifers were fed differing amounts of the same silage-based diet. Mammary glands of 18 crossbred heifers Holstein:Gyr underwent a single mammary ultrasound exam immediately before heifer slaughter, which took place when heifers weighed 142.0 ± 8.0 kg and were 200 d old. The 4 mammary glands of each heifer were evaluated using a real-time B-mode ultrasound machine equipped with a 6.5-MHz micro-convex transducer. Digital images (8-bit) of glands were obtained and PAR was identified within gland. Average pixel values per unit of PAR area were determined for each gland and analyzed at the level of heifer. Pixel results were interpreted on the basis that lower average pixel values reflect PAR with relatively high amounts of protein as opposed to fat. To help validate that the pixel value within PAR is associated with composition of PAR, pixel findings were compared with histological [number of adipocytes in PAR (Nad) and epithelial area in PAR (Ep)] and biochemical [percent crude protein in PAR (%CP), percent ether extract in PAR (%EE), PAR weight (WPAR), and mammary fat pad weight (WFAT)] composition of PAR in these same heifers. Within PAR, %EE and WFAT were positively correlated with pixel values, whereas %CP, Ep, and Nad were negatively correlated. Parenchyma weight did not correlate

  1. Mammary extracellular matrix directs differentiation of testicular and embryonic stem cells to form functional mammary glands in vivo. (United States)

    Bruno, Robert D; Fleming, Jodie M; George, Andrea L; Boulanger, Corinne A; Schedin, Pepper; Smith, Gilbert H


    Previously, we demonstrated the ability of the normal mammary microenvironment (niche) to direct non-mammary cells including testicular and embryonic stem cells (ESCs) to adopt a mammary epithelial cell (MEC) fate. These studies relied upon the interaction of transplanted normal MECs with non-mammary cells within the mammary fat-pads of recipient mice that had their endogenous epithelium removed. Here, we tested whether acellular mammary extracellular matrix (mECM) preparations are sufficient to direct differentiation of testicular-derived cells and ESCs to form functional mammary epithelial trees in vivo. We found that mECMs isolated from adult mice and rats were sufficient to redirect testicular derived cells to produce normal mammary epithelial trees within epithelial divested mouse mammary fat-pads. Conversely, ECMs isolated from omental fat and lung did not redirect testicular cells to a MEC fate, indicating the necessity of tissue specific components of the mECM. mECM preparations also completely inhibited teratoma formation from ESC inoculations. Further, a phenotypically normal ductal outgrowth resulted from a single inoculation of ESCs and mECM. To the best of our knowledge, this is the first demonstration of a tissue specific ECM driving differentiation of cells to form a functional tissue in vivo.

  2. LIBO accelerates

    CERN Multimedia


    The prototype module of LIBO, a linear accelerator project designed for cancer therapy, has passed its first proton-beam acceleration test. In parallel a new version - LIBO-30 - is being developed, which promises to open up even more interesting avenues.

  3. Pubertally Initiated High-Fat Diet Promotes Mammary Tumorigenesis in Obesity-Prone FVB Mice Similarly to Obesity-Resistant BALB/c Mice

    Directory of Open Access Journals (Sweden)

    Yirong Zhu


    Full Text Available Premenopausal breast cancer is associated with increased animal fat consumption among normal-weight but not overweight women. Our previous findings in obesity-resistant BALB/c mice showed that a diet high in saturated animal fat (HFD promotes mammary tumorigenesis in both DMBA carcinogenesis and Trp53-null transplant models. Having made these observations in BALB/c mice, which have very modest HFD weight gain, we determined the effects of HFD in FVB mice, which gain significant weight on HFD. Three-week-old FVB mice fed a low-fat diet or HFD were subjected to 7,12-dimethylbenz[a]anthracene-induced carcinogenesis. Like BALB/c mice, HFD promoted mammary tumorigenesis. Development of tumors largely occurred prior to mice becoming obese, indicating the role of animal-derived HFD rather than resulting obesity in tumor promotion. Also similar to BALB/c mice, early-occurring adenosquamous mammary tumors were abundant among HFD-fed FVB mice. Tumors from HFD mice also had increased intra-tumor M2 macrophages. Prior to tumor development, HFD accelerated normal mammary gland development and increased mammary M2 macrophages, similarly to BALB/c mice. The promotional effects of puberty-initiated HFD on carcinogen-induced mammary cancer are thus largely weight gain-independent. Like BALB/c mice, HFD promoted adenosquamous tumors, suggesting a role for early age HFD in promoting this subtype of triple negative mammary cancer. M2 macrophage recruitment was common to both mouse strains. We speculate that a similar effect of HFD on immune function may contribute to epidemiological findings of increased breast cancer risk in young, premenopausal, normal-weight women who consume a diet high in saturated animal fat.

  4. Accelerating Inspire

    CERN Document Server



    CERN has been involved in the dissemination of scientific results since its early days and has continuously updated the distribution channels. Currently, Inspire hosts catalogues of articles, authors, institutions, conferences, jobs, experiments, journals and more. Successful orientation among this amount of data requires comprehensive linking between the content. Inspire has lacked a system for linking experiments and articles together based on which accelerator they were conducted at. The purpose of this project has been to create such a system. Records for 156 accelerators were created and all 2913 experiments on Inspire were given corresponding MARC tags. Records of 18404 accelerator physics related bibliographic entries were also tagged with corresponding accelerator tags. Finally, as a part of the endeavour to broaden CERN's presence on Wikipedia, existing Wikipedia articles of accelerators were updated with short descriptions and links to Inspire. In total, 86 Wikipedia articles were updated. This repo...

  5. Induction accelerators

    CERN Document Server

    Takayama, Ken


    A broad class of accelerators rests on the induction principle whereby the accelerating electrical fields are generated by time-varying magnetic fluxes. Particularly suitable for the transport of bright and high-intensity beams of electrons, protons or heavy ions in any geometry (linear or circular) the research and development of induction accelerators is a thriving subfield of accelerator physics. This text is the first comprehensive account of both the fundamentals and the state of the art about the modern conceptual design and implementation of such devices. Accordingly, the first part of the book is devoted to the essential features of and key technologies used for induction accelerators at a level suitable for postgraduate students and newcomers to the field. Subsequent chapters deal with more specialized and advanced topics.

  6. Melatonin and mammary cancer: a short review. (United States)

    Sánchez-Barceló, E J; Cos, S; Fernández, R; Mediavilla, M D


    Melatonin is an indolic hormone produced mainly by the pineal gland. The former hypothesis of its possible role in mammary cancer development was based on the evidence that melatonin down-regulates some of the pituitary and gonadal hormones that control mammary gland development and which are also responsible for the growth of hormone-dependent mammary tumors. Furthermore, melatonin could act directly on tumoral cells, as a naturally occurring antiestrogen, thereby influencing their proliferative rate. The first reports revealed a low plasmatic melatonin concentration in women with estrogen receptor (ER)-positive breast tumors. However, later studies on the possible role of melatonin on human breast cancer have been scarce and mostly of an epidemiological type. These studies described a low incidence of breast tumors in blind women as well as an inverse relationship between breast cancer incidence and the degree of visual impairment. Since light inhibits melatonin secretion, the relative increase in the melatonin circulating levels in women with a decreased light input could be interpreted as proof of the protective role of melatonin on mammary carcinogenesis. From in vivo studies on animal models of chemically induced mammary tumorigenesis, the general conclusion is that experimental manipulations activating the pineal gland or the administration of melatonin lengthens the latency and reduces the incidence and growth rate of mammary tumors, while pinealectomy usually has the opposite effects. Melatonin also reduces the incidence of spontaneous mammary tumors in different kinds of transgenic mice (c-neu and N-ras) and mice from strains with a high tumoral incidence. In vitro experiments, carried out with the ER-positive MCF-7 human breast cancer cells, demonstrated that melatonin, at a physiological concentration (1 nM) and in the presence of serum or estradiol: (a) inhibits, in a reversible way, cell proliferation, (b) increases the expression of p53 and p21WAF1

  7. Mammary Gland Ontegeny and Neoplasia in Oxytocin Deficient Mice. (United States)


    be protective. The technical objectives of this proposal as follows. 1) Determine the prevalence of mammary neoplasia in the progeny of MMTV-infected...WT mice to develop mammary neoplasia when exposed in vivo to ovarian steroid hormones. If oxytocin is shown to be an important factor in breast cancer, exogenous oxytocin may be a potential safe, non-toxic measure in its prevention.

  8. Identity and dynamics of mammary stem cells during branching morphogenesis

    NARCIS (Netherlands)

    Scheele, Colinda L.G.J.; Hannezo, Edouard; Muraro, Mauro J.; Zomer, Anoek; Langedijk, Nathalia S.M.; Van Oudenaarden, Alexander; Simons, Benjamin D; Van Rheenen, Jacco


    During puberty, the mouse mammary gland develops into a highly branched epithelial network. Owing to the absence of exclusive stem cell markers, the location, multiplicity, dynamics and fate of mammary stem cells (MaSCs), which drive branching morphogenesis, are unknown. Here we show that

  9. Mammary Development and Breast Cancer: A Wnt Perspective (United States)

    Yu, Qing Cissy; Verheyen, Esther M.; Zeng, Yi Arial


    The Wnt pathway has emerged as a key signaling cascade participating in mammary organogenesis and breast oncogenesis. In this review, we will summarize the current knowledge of how the pathway regulates stem cells and normal development of the mammary gland, and discuss how its various components contribute to breast carcinoma pathology. PMID:27420097

  10. Induction of mammary gland tumor in female Sprague- Dawley rats ...

    African Journals Online (AJOL)



    Jul 12, 2010 ... hormone sensitivity and histology. There is no other animal tumor comparable to these models because of the similarity in the function and structure of certain rat mammary tumors to hormone-sensitive human breast cancer (Young and Hallowers, 1973). Mammary gland LA7 cells were isolated in 1979 ...

  11. Resident macrophages influence stem cell activity in the mammary gland

    NARCIS (Netherlands)

    Gyorki, D.E.; Asselin-Labat, M.L.; Rooijen, van N.; Lindeman, G.J.; Visvader, J.E.


    Introduction Macrophages in the mammary gland are essential for morphogenesis of the ductal epithelial tree and have been implicated in promoting breast tumor metastasis. Although it is well established that macrophages influence normal mammopoiesis, the mammary cell types that these accessory cells

  12. Infrared Thermography in Dogs with Mammary Tumors and Healthy Dogs. (United States)

    Pavelski, M; Silva, D M; Leite, N C; Junior, D A; de Sousa, R S; Guérios, S D; Dornbusch, P T


    Infrared thermography is a painless, noninvasive, nonionizing diagnostic imaging exam used in human medicine as an auxiliary tool for breast cancer diagnosis in women. Define thermographic mean temperatures of healthy mammary glands and compare these temperatures with those of mammary glands with tumors in dogs. Fifty client-owned female dogs were evaluated, including 20 with histopathologically confirmed mammary tumor and 30 clinically healthy (control). A randomized study using infrared thermography analyzed each mammary gland of the animals from the control group and mammary glands with tumors from the tumor group, then the thermographic temperatures obtained were compared. Thermographic exam was performed in a temperature-controlled room with a cooled thermographic camera-Flir E-40 (Flir Systems(®) ) There was significantly a higher temperature in the caudal abdominal and inguinal mammary glands than the other glands in the healthy group (P < .05). Dogs with mammary tumors had significantly higher thermographic temperature compared with unaffected glands regardless of the tumor size and the location (P < .05). The technique seems to be able to assess for the presence of neoplasia within the mammary tissue in bitches. Further investigation is necessary to determine the impact of this technique when adopted clinically. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

  13. Lactating Vulva Mammary Tissue in a Nigerian | Igwegbe | Nigerian ...

    African Journals Online (AJOL)

    ... cystic mass in the right labium majus that developed rapidly in the early puerperium following her 5th confinement. Histology of the completely excised cyst revealed a secretory mammary tissue. There was no recurrence ten months after surgery while breastfeeding. Key Words: lactation, vulva, Mammary tissue, Nigerian

  14. Bovine mammary stem cells: Cell biology meets production agriculture (United States)

    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 ...

  15. Cosmic Acceleration (United States)

    Bean, Rachel


    In this series of lectures we review observational evidence for, and theoretical investigations into, cosmic acceleration and dark energy. The notes are in four sections. First I review the basic cosmological formalism to describe the expansion history of the universe and how distance measures are defined. The second section covers the evidence for cosmic acceleration from cosmic distance measurements. Section 3 discusses the theoretical avenues being considered to explain the cosmological observations. Section 4 discusses how the growth of inhomogeneities and large scale structure observations might help us pin down the theoretical origin of cosmic acceleration.

  16. Adiponectin haploinsufficiency promotes mammary tumor development in MMTV-PyVT mice by modulation of phosphatase and tensin homolog activities.

    Directory of Open Access Journals (Sweden)

    Janice B B Lam

    Full Text Available Adiponectin is an adipokine possessing beneficial effects on obesity-related medical complications. A negative association of adiponectin levels with breast cancer development has been demonstrated. However, the precise role of adiponectin deficiency in mammary carcinogenesis remains elusive.In the present study, MMTV-polyomavirus middle T antigen (MMTV-PyVT transgenic mice with reduced adiponectin expressions were established and the stromal effects of adiponectin haploinsufficiency on mammary tumor development evaluated. In mice from both FVB/N and C57BL/6J backgrounds, insufficient adiponectin production promoted mammary tumor onset and development. A distinctive basal-like subtype of tumors, with a more aggressive phenotype, was derived from adiponectin haplodeficient MMTV-PyVT mice. Comparing with those from control MMTV-PyVT mice, the isolated mammary tumor cells showed enhanced tumor progression in re-implanted nude mice, accelerated proliferation in primary cultures, and hyperactivated phosphatidylinositol-3-kinase (PI3K/Akt/beta-catenin signaling, which at least partly attributed to the decreased phosphatase and tensin homolog (PTEN activities. Further analysis revealed that PTEN was inactivated by a redox-regulated mechanism. Increased association of PTEN-thioredoxin complexes was detected in tumors derived from mice with reduced adiponectin levels. The activities of thioredoxin (Trx1 and thioredoxin reductase (TrxR1 were significantly elevated, whereas treatment with either curcumin, an irreversible inhibitor of TrxR1, or adiponectin largely attenuated their activities and resulted in the re-activation of PTEN in these tumor cells. Moreover, adiponectin could inhibit TrxR1 promoter-mediated transcription and restore the mRNA expressions of TrxR1.Adiponectin haploinsufficiency facilitated mammary tumorigenesis by down-regulation of PTEN activity and activation of PI3K/Akt signalling pathway through a mechanism involving Trx1/TrxR1

  17. Luminal progenitors restrict their lineage potential during mammary gland development. (United States)

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


    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.

  18. Huntingtin Regulates Mammary Stem Cell Division and Differentiation

    Directory of Open Access Journals (Sweden)

    Salah Elias


    Full Text Available Little is known about the mechanisms of mitotic spindle orientation during mammary gland morphogenesis. Here, we report the presence of huntingtin, the protein mutated in Huntington’s disease, in mouse mammary basal and luminal cells throughout mammogenesis. Keratin 5-driven depletion of huntingtin results in a decreased pool and specification of basal and luminal progenitors, and altered mammary morphogenesis. Analysis of mitosis in huntingtin-depleted basal progenitors reveals mitotic spindle misorientation. In mammary cell culture, huntingtin regulates spindle orientation in a dynein-dependent manner. Huntingtin is targeted to spindle poles through its interaction with dynein and promotes the accumulation of NUMA and LGN. Huntingtin is also essential for the cortical localization of dynein, dynactin, NUMA, and LGN by regulating their kinesin 1-dependent trafficking along astral microtubules. We thus suggest that huntingtin is a component of the pathway regulating the orientation of mammary stem cell division, with potential implications for their self-renewal and differentiation properties.

  19. Mammary Development and Breast Cancer: The Role of Stem Cells (United States)

    Ercan, C.; van Diest, P.J.; Vooijs, M.


    The mammary gland is a highly regenerative organ that can undergo multiple cycles of proliferation, lactation and involution, a process controlled by stem cells. The last decade much progress has been made in the identification of signaling pathways that function in these stem cells to control self-renewal, lineage commitment and epithelial differentiation in the normal mammary gland. The same signaling pathways that control physiological mammary development and homeostasis are also often found deregulated in breast cancer. Here we provide an overview on the functional and molecular identification of mammary stem cells in the context of both normal breast development and breast cancer. We discuss the contribution of some key signaling pathways with an emphasis on Notch receptor signaling, a cell fate determination pathway often deregulated in breast cancer. A further understanding of the biological roles of the Notch pathway in mammary stem cell behavior and carcinogenesis might be relevant for the development of future therapies. PMID:21506923

  20. Mammary epithelial cells isolated from milk are a valuable, non-invasive source of mammary transcripts

    Directory of Open Access Journals (Sweden)

    Marion eBoutinaud


    Full Text Available Milk is produced in the udder by mammary epithelial cells (MEC. Milk contains MEC, which are gradually exfoliated from the epithelium during lactation. Isolation of MEC from milk using immunomagnetic separation may be a useful non-invasive method to investigate transcriptional regulations in ruminants’ udder. This review aims to describe the process of isolating MEC from milk, to provide an overview on the studies that use this method to analyze gene expression by qRT PCR and to evaluate the validity of this method by analysing and comparing the results between studies. In several goat and cow studies, consistent reductions in alpha-lactalbumin mRNA levels during once-daily milking (ODM and in SLC2A1 mRNA level during feed restriction are observed. The effect of ODM on alpha-lactalbumin mRNA level was similarly observed in milk isolated MEC and mammary biopsy. Moreover, we and others showed decreasing alpha-lactalbumin and increasing BAX mRNA levels with advanced stages of lactation in dairy cows and buffalo. The relevance of using the milk-isolated MEC method to analyze mammary gene expression is proven, as the transcript variations were also consistent with milk yield and composition variations under the effect of different factors such as prolactin inhibition or photoperiod. . However, the RNA from milk-isolated MEC is particularly sensitive to degradation. This could explain the differences obtained between milk-isolated MEC and mammary biopsy in two studies where gene expression was compared using qRT-PCR or RNA Sequencing analyses. As a conclusion, when the RNA quality is conserved, MEC isolated from milk are a valuable, non-invasive source of mammary mRNA to study various factors that impact milk yield and composition (ODM, feeding level, endocrine status, photoperiod modulation and stage of lactation.

  1. Horizontal Accelerator (United States)

    Federal Laboratory Consortium — The Horizontal Accelerator (HA) Facility is a versatile research tool available for use on projects requiring simulation of the crash environment. The HA Facility is...

  2. Accelerated construction (United States)


    Accelerated Construction Technology Transfer (ACTT) is a strategic process that uses various innovative techniques, strategies, and technologies to minimize actual construction time, while enhancing quality and safety on today's large, complex multip...

  3. Mammary gland tumors in a male Cocker Spaniel. (United States)

    Kwon, Soon-Chan; Yoo, Dae-Young; Ko, Minho; Lee, Kwon-Young; Kwak, Ho-Hyun; Park, In-Chul; Hwang, In-Koo; Choi, Jung-Hoon; Chung, Jin-Young


    Mammary gland tumors are the most common tumors in sexually intact female dogs; however, they are rare in male dogs. This study was conducted to investigate the relationship between sexual hormones and mammary gland tumors in a male dog. A 13-year-old, intact male Cocker Spaniel presented to the Veterinary Teaching Hospital of Kangwon National University, Republic of Korea, with an acute right ruptured caudal abdominal mass. Physical examination revealed a 14 × 14 cm ruptured mass in the right caudal abdomen, as well as a 1.5 × 1.5 cm mass in the first right mammary gland. The estrogen and progesterone concentrations in serum were within normal levels. Total mastectomy was done on the right side mammary glands. Following surgery, the site was fully recovered; however, a mass that had grown to 2 × 2 cm was found in the left fifth mammary gland and a testis tumor was also found over the period of 4 months. Mastectomy was performed on the left caudal mammary gland and castration was also performed. After the final surgery, the dog fully recovered. Histopathological examination of all three masses revealed high grade mammary adenocarcinoma in the mammary gland and the testis was diagnosed as Leydig cell adenoma. Immunohistochemical analysis revealed that the estrogen and progesterone receptors were expressed on limited cells in mammary and testis tumors. The results of this study suggest that mammary tumors and testes tumors can occur in male dogs without relationship to female sexual hormone.

  4. Genetic mechanisms in Apc-mediated mammary tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Mari Kuraguchi


    Full Text Available Many components of Wnt/beta-catenin signaling pathway also play critical roles in mammary tumor development, yet the role of the tumor suppressor gene APC (adenomatous polyposis coli in breast oncongenesis is unclear. To better understand the role of Apc in mammary tumorigenesis, we introduced conditional Apc mutations specifically into two different mammary epithelial populations using K14-cre and WAP-cre transgenic mice that express Cre-recombinase in mammary progenitor cells and lactating luminal cells, respectively. Only the K14-cre-mediated Apc heterozygosity developed mammary adenocarcinomas demonstrating histological heterogeneity, suggesting the multilineage progenitor cell origin of these tumors. These tumors harbored truncation mutation in a defined region in the remaining wild-type allele of Apc that would retain some down-regulating activity of beta-catenin signaling. Activating mutations at codons 12 and 61 of either H-Ras or K-Ras were also found in a subset of these tumors. Expression profiles of acinar-type mammary tumors from K14-cre; Apc(CKO/+ mice showed luminal epithelial gene expression pattern, and clustering analysis demonstrated more correlation to MMTV-neu model than to MMTV-Wnt1. In contrast, neither WAP-cre-induced Apc heterozygous nor homozygous mutations resulted in predisposition to mammary tumorigenesis, although WAP-cre-mediated Apc deficiency resulted in severe squamous metaplasia of mammary glands. Collectively, our results suggest that not only the epithelial origin but also a certain Apc mutations are selected to achieve a specific level of beta-catenin signaling optimal for mammary tumor development and explain partially the colon- but not mammary-specific tumor development in patients that carry germline mutations in APC.

  5. LINEAR ACCELERATOR (United States)

    Christofilos, N.C.; Polk, I.J.


    Improvements in linear particle accelerators are described. A drift tube system for a linear ion accelerator reduces gap capacity between adjacent drift tube ends. This is accomplished by reducing the ratio of the diameter of the drift tube to the diameter of the resonant cavity. Concentration of magnetic field intensity at the longitudinal midpoint of the external sunface of each drift tube is reduced by increasing the external drift tube diameter at the longitudinal center region.

  6. Development of mammary glands of fat sheep submitted to restricted feeding during late pregnancy

    DEFF Research Database (Denmark)

    Nørgaard, J V; Nielsen, M O; Theil, P K


    Mammary gland development in sheep occurs mainly during puberty and pregnancy. We have investigated the effects of a late gestation feed restriction on mammary gland development in sheep.......Mammary gland development in sheep occurs mainly during puberty and pregnancy. We have investigated the effects of a late gestation feed restriction on mammary gland development in sheep....

  7. Mammary gland pathologies in the parturient buffalo

    Directory of Open Access Journals (Sweden)

    G N Purohit


    Full Text Available Parturition related mammary gland pathologies in the buffalo appear to be low on accord of anatomic (longer teat length, thicker streak canal and physiologic (lower cisternal storage of secreted milk, lower milk production differences with cattle. Hemolactia, udder edema and hypogalactia usually occur in the buffalo due to physiologic changes around parturition however mastitis involves pathologic changes in the udder and teats; the incidence of mastitis is however lower compared to cattle. The incidence and therapy of hemolactia, udder edema and hypogalactia are mentioned and the risk factors, incidence, diagnosis, therapy and prevention for mastitis in buffalo are also described.

  8. Exploring the gain of function contribution of AKT to mammary tumorigenesis in mouse models.

    Directory of Open Access Journals (Sweden)

    Carmen Blanco-Aparicio

    Full Text Available Elevated expression of AKT has been noted in a significant percentage of primary human breast cancers, mainly as a consequence of the PTEN/PI3K pathway deregulation. To investigate the mechanistic basis of the AKT gain of function-dependent mechanisms of breast tumorigenesis, we explored the phenotype induced by activated AKT transgenes in a quantitative manner. We generated several transgenic mice lines expressing different levels of constitutively active AKT in the mammary gland. We thoroughly analyzed the preneoplastic and neoplastic mammary lesions of these mice and correlated the process of tumorigenesis to AKT levels. Finally, we analyzed the impact that a possible senescent checkpoint might have in the tumor promotion inhibition observed, crossing these lines to mammary specific p53(R172H mutant expression, and to p27 knock-out mice. We analyzed the benign, premalignant and malignant lesions extensively by pathology and at molecular level analysing the expression of proteins involved in the PI3K/AKT pathway and in cellular senescence. Our findings revealed an increased preneoplastic phenotype depending upon AKT signaling which was not altered by p27 or p53 loss. However, p53 inactivation by R172H point mutation combined with myrAKT transgenic expression significantly increased the percentage and size of mammary carcinoma observed, but was not sufficient to promote full penetrance of the tumorigenic phenotype. Molecular analysis suggest that tumors from double myrAKT;p53(R172H mice result from acceleration of initiated p53(R172H tumors and not from bypass of AKT-induced oncogenic senescence. Our work suggests that tumors are not the consequence of the bypass of senescence in MIN. We also show that AKT-induced oncogenic senescence is dependent of pRb but not of p53. Finally, our work also suggests that the cooperation observed between mutant p53 and activated AKT is due to AKT-induced acceleration of mutant p53-induced tumors. Finally, our

  9. Reconstitution of mammary epithelial morphogenesis by murine embryonic stem cells undergoing hematopoietic stem cell differentiation.

    Directory of Open Access Journals (Sweden)

    Shuxian Jiang


    Full Text Available Mammary stem cells are maintained within specific microenvironments and recruited throughout lifetime to reconstitute de novo the mammary gland. Mammary stem cells have been isolated through the identification of specific cell surface markers and in vivo transplantation into cleared mammary fat pads. Accumulating evidence showed that during the reformation of mammary stem cell niches by dispersed epithelial cells in the context of the intact epithelium-free mammary stroma, non-mammary epithelial cells may be sequestered and reprogrammed to perform mammary epithelial cell functions and to adopt mammary epithelial characteristics during reconstruction of mammary epithelium in regenerating mammary tissue in vivo.To examine whether other types of progenitor cells are able to contribute to mammary branching morphogenesis, we examined the potential of murine embryonic stem (mES cells, undergoing hematopoietic differentiation, to support mammary reconstitution in vivo. We observed that cells from day 14 embryoid bodies (EBs under hematopoietic differentiation condition, but not supernatants derived from these cells, when transplanted into denuded mammary fat pads, were able to contribute to both the luminal and myoepithelial lineages in branching ductal structures resembling the ductal-alveolar architecture of the mammary tree. No teratomas were observed when these cells were transplanted in vivo.Our data provide evidence for the dominance of the tissue-specific mammary stem cell niche and its role in directing mES cells, undergoing hematopoietic differentiation, to reprogram into mammary epithelial cells and to promote mammary epithelial morphogenesis. These studies should also provide insights into regeneration of damaged mammary gland and the role of the mammary microenvironment in reprogramming cell fate.

  10. Progesterone induces adult mammary stem cell expansion. (United States)

    Joshi, Purna A; Jackson, Hartland W; Beristain, Alexander G; Di Grappa, Marco A; Mote, Patricia A; Clarke, Christine L; Stingl, John; Waterhouse, Paul D; Khokha, Rama


    Reproductive history is the strongest risk factor for breast cancer after age, genetics and breast density. Increased breast cancer risk is entwined with a greater number of ovarian hormone-dependent reproductive cycles, yet the basis for this predisposition is unknown. Mammary stem cells (MaSCs) are located within a specialized niche in the basal epithelial compartment that is under local and systemic regulation. The emerging role of MaSCs in cancer initiation warrants the study of ovarian hormones in MaSC homeostasis. Here we show that the MaSC pool increases 14-fold during maximal progesterone levels at the luteal dioestrus phase of the mouse. Stem-cell-enriched CD49fhi cells amplify at dioestrus, or with exogenous progesterone, demonstrating a key role for progesterone in propelling this expansion. In aged mice, CD49fhi cells display stasis upon cessation of the reproductive cycle. Progesterone drives a series of events where luminal cells probably provide Wnt4 and RANKL signals to basal cells which in turn respond by upregulating their cognate receptors, transcriptional targets and cell cycle markers. Our findings uncover a dynamic role for progesterone in activating adult MaSCs within the mammary stem cell niche during the reproductive cycle, where MaSCs are putative targets for cell transformation events leading to breast cancer.

  11. Significance of EZH2 expression in canine mammary tumors. (United States)

    Choi, Hyun-Ji; Jang, Sungwoong; Ryu, Jae-Eun; Lee, Hyo-Ju; Lee, Han-Byul; Ahn, Woo-Sung; Kim, Hye-Jin; Lee, Hyo-Jin; Lee, Hee Jin; Gong, Gyung-Yub; Son, Woo-Chan


    Current studies report that aberrations in epigenetic regulators or chromatin modifications are related to tumor development and maintenance. EZH2 (Enhancer of zeste homolog 2) is one of the catalytic subunits of Polycomb repressive complex 2, a crucial epigenetic regulator. EZH2 has a master regulatory function in such processes as cell proliferation, stem cell differentiation, and early embryogenesis. In humans, EZH2 is linked to oncogenic function in several carcinomas, including breast cancer, and dysregulation of EZH2 has been particularly associated with loss of differentiation and the development of poorly differentiated breast cancer. In our present study, we were interested in determining whether EZH2 is increased in canine mammary tumors, which show similarities to human breast cancer. Investigation of the expression of EZH2 in canine mammary tumors revealed that EZH2 protein was overexpressed in canine mammary carcinomas, as in human breast cancer. In addition, the immunohistochemical expression level of EZH2 was associated with the degree of malignancy in canine mammary carcinoma. This is the first report to describe EZH2 expression in canine mammary tumors. Because the expression of EZH2 was similar in canine mammary carcinoma and human breast cancer, spontaneous canine mammary tumors may be a suitable model for studying EZH2 and treatment development.

  12. Disruption of reelin signaling alters mammary gland morphogenesis (United States)

    Khialeeva, Elvira; Lane, Timothy F.; Carpenter, Ellen M.


    Reelin signaling is required for appropriate cell migration and ductal patterning during mammary gland morphogenesis. Dab1, an intracellular adaptor protein activated in response to reelin signaling, is expressed in the developing mammary bud and in luminal epithelial cells in the adult gland. Reelin protein is expressed in a complementary pattern, first in the epithelium overlying the mammary bud during embryogenesis and then in the myoepithelium and periductal stroma in the adult. Deletion in mouse of either reelin or Dab1 induced alterations in the development of the ductal network, including significant retardation in ductal elongation, decreased terminal branching, and thickening and disorganization of the luminal wall. At later stages, some mutant glands overcame these early delays, but went on to exhibit enlarged and chaotic ductal morphologies and decreased terminal branching: these phenotypes are suggestive of a role for reelin in spatial patterning or structural organization of the mammary epithelium. Isolated mammary epithelial cells exhibited decreased migration in response to exogenous reelin in vitro, a response that required Dab1. These observations highlight a role for reelin signaling in the directed migration of mammary epithelial cells driving ductal elongation into the mammary fat pad and provide the first evidence that reelin signaling may be crucial for regulating the migration and organization of non-neural tissues. PMID:21266412

  13. Sequencing the transcriptome of milk production: milk trumps mammary tissue (United States)


    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. Mammary remodeling in primiparous and multiparous dairy goats during lactation

    DEFF Research Database (Denmark)

    Safayi, Sina; Theil, Peter Kappel; Elbrønd, Vibeke Sødring


    obtained from both mammary glands of 3 PP and 6 MP (≥2 parity) dairy goats at parturition (d 1), d 10, 60, and 180 of lactation. Gene transcription relating to MEC turnover and vascular function was quantified by real-time reverse transcription-PCR, mammary morphology was characterized (quantitative......Milk production is generally lower but lactation persistency higher in primiparous (PP) than in multiparous (MP) goats. This may be related to differences in development and maintenance of mammary gland function, but the underlying mechanisms are not well understood. The present study aimed...

  15. Suitability of tissue prints for immunocytochemical diagnosis of mammary cancer. (United States)

    Surowiak, P; Dziegiel, P; Zabel, M; Zasławski, R


    The present study was aimed at evaluating suitability of tissue prints for immunocytochemical evaluation of mammary cancer cells. The prints, originating from 30 cases of mammary cancer were studied using immunocytochemical reactions with monoclonal antibodies against estrogen and progesterone receptors, metallothionein (MT), P-glycoprotein and cytokeratins (clone LP34). Expression of individual antigens was assessed using the scale in which intensity of the colour reaction and percentage of positive cells were taken into account. The obtained results did not differ qualitatively or quantitatively from those obtained in paraffin sections. The studies have shown that tissue prints can be used for reliable immunocytochemical evaluation of expression of various proteins in mammary cancer cells.

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

    Directory of Open Access Journals (Sweden)

    Leonardo Secchin Canale


    Full Text Available 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.

  17. Mammary artery harvesting using the Da Vinci Si robotic system (United States)

    Canale, Leonardo Secchin; Bonatti, Johannes


    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

  18. Delivering the message: epimorphin and mammary epithelial morphogenesis. (United States)

    Radisky, Derek C; Hirai, Yohei; Bissell, Mina J


    The mammary gland consists of a highly branched tubular epithelium surrounded by a complex mesenchymal stroma. Epimorphin is an extracellular protein that is expressed by mammary mesenchymal cells that directs epithelial morphogenesis. Depending upon the context of presentation--polar versus apolar--epimorphin can selectively direct two key processes of tubulogenesis: branching morphogenesis (processes involved in tubule initiation and extension) and luminal morphogenesis (required for enlargement of tubule caliber). Here, we outline the fundamentals of mammary gland development and describe the function of epimorphin in these processes. We conclude with a review of recent studies that suggest similar morphogenic roles for epimorphin in other glandular organs.

  19. Mammary-Specific Ablation of the Calcium-Sensing Receptor During Lactation Alters Maternal Calcium Metabolism, Milk Calcium Transport, and Neonatal Calcium Accrual (United States)

    Mamillapalli, Ramanaiah; VanHouten, Joshua; Dann, Pamela; Bikle, Daniel; Chang, Wenhan; Brown, Edward


    To meet the demands for milk calcium, the lactating mother adjusts systemic calcium and bone metabolism by increasing dietary calcium intake, increasing bone resorption, and reducing renal calcium excretion. As part of this adaptation, the lactating mammary gland secretes PTHrP into the maternal circulation to increase bone turnover and mobilize skeletal calcium stores. Previous data have suggested that, during lactation, the breast relies on the calcium-sensing receptor (CaSR) to coordinate PTHrP secretion and milk calcium transport with calcium availability. To test this idea genetically, we bred BLG-Cre mice with CaSR-floxed mice to ablate the CaSR specifically from mammary epithelial cells only at the onset of lactation (CaSR-cKO mice). Loss of the CaSR in the lactating mammary gland did not disrupt alveolar differentiation or milk production. However, it did increase the secretion of PTHrP into milk and decreased the transport of calcium from the circulation into milk. CaSR-cKO mice did not show accelerated bone resorption, but they did have a decrease in bone formation. Loss of the mammary gland CaSR resulted in hypercalcemia, decreased PTH secretion, and increased renal calcium excretion in lactating mothers. Finally, loss of the mammary gland CaSR resulted in decreased calcium accrual by suckling neonates, likely due to the combination of increased milk PTHrP and decreased milk calcium. These results demonstrate that the mammary gland CaSR coordinates maternal bone and calcium metabolism, calcium transport into milk, and neonatal calcium accrual during lactation. PMID:23782944

  20. Stromal and Epithelial Caveolin-1 Both Confer a Protective Effect Against Mammary Hyperplasia and Tumorigenesis : Caveolin-1 Antagonizes Cyclin D1 Function in Mammary Epithelial Cells


    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.


    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 ...

  1. Age Modifies the Effect of 2-MeV Fast Neutrons on Rat Mammary Carcinogenesis. (United States)

    Imaoka, Tatsuhiko; Nishimura, Mayumi; Daino, Kazuhiro; Hosoki, Ayaka; Takabatake, Masaru; Kokubo, Toshiaki; Doi, Kazutaka; Showler, Kaye; Nishimura, Yukiko; Moriyama, Hitomi; Morioka, Takamitsu; Shimada, Yoshiya; Kakinuma, Shizuko


    The relative biological effectiveness (RBE) of neutrons depends on their physical nature (e.g., energy) and the biological context (e.g., end points, materials). From the perspective of radiological protection, age is an important biological context that influences radiation-related cancer risk, but very few studies have addressed its potential impact on neutron effects. We therefore investigated the influence of age on the effect of accelerator-generated fast neutrons (mean energy, ∼2 MeV) in an animal model of breast carcinogenesis. Female Sprague-Dawley rats at 1, 3 and 7 weeks of age were irradiated with fast neutrons at absorbed doses of 0.0485-0.97 Gy. All animals were kept under specific pathogen-free conditions and screened weekly for mammary tumors by palpation until they were 90 weeks old. Tumors were diagnosed based on histology. Mathematical modeling was used to analyze mammary cancer incidence, collectively using data from this study and a previously reported experiment on 137Cs gamma rays. The results indicate that neutron irradiation elevated the risk of palpable mammary carcinoma with a linear dose response, the slope of which depended on age at time of irradiation. The RBE of neutron radiation was 7.5 ± 3.4, 9.3 ± 3.5 and 26.1 ± 8.9 (mean ± SE) for animals exposed at 1, 3 and 7 weeks of age, respectively. Our results indicate that age of the animal is an important factor influencing the effect of fast neutrons on breast cancer risk.

  2. Activating Transcription Factor-5 Knockdown Reduces Aggressiveness of Mammary Tumor Cells and Attenuates Mammary Tumor Growth

    Directory of Open Access Journals (Sweden)

    Sarit Ben-Shmuel


    Full Text Available Activating transcription factor-5 (ATF5 is an anti-apoptotic factor and has been implicated in enhancing the survival of cancer cells under stress and in regulating the autophagy process. Targeting ATF5 in anticancer therapy may be particularly attractive because of its differential role in cancer cells than in non-transformed cells, thus allowing specificity of the treatment. Using the delivery of short hairpin RNA vectors into the Mvt1 and Met1 cell lines, we tested the role of ATF5 in the development of mammary tumors in vivo and in regulating proliferation and migration of these cells in vitro. In this study, we demonstrate that knockdown of ATF5 (ATF5-KD in both cell lines results in a decreased tumor volume and weight, as well as in a reduced proliferation rate and migratory potential of the cells. In addition, ATF5-KD led to an increased autophagy flux and a shift in the sub-populations comprising Mvt1 cells from the aggressive CD24-positive cells toward less aggressive CD24-negative cells. Taken together, these findings suggest that ATF5 plays an important role in enhancing mammary tumor cells overall aggressiveness and in promoting mammary tumor growth and emphasize the possible benefit of anti-ATF5 therapy in breast cancer patients, particularly, against tumors characterized with the positive expression of cell surface CD24.

  3. Mammary Stem Cell Research in Veterinary Science: An Update (United States)

    Borena, Bizunesh M.; Bussche, Leen; Burvenich, Christian; Duchateau, Luc


    The mammary gland is an organ with a remarkable regenerative capacity that can undergo multiple cycles of proliferation, lactation, and involution. Growing evidence suggests that these changes are driven by the coordinated division and differentiation of mammary stem cell populations (MaSC). Whereas information regarding MaSC and their role in comparative mammary gland physiology is readily available in human and mice, such information remains scarce in most veterinary mammal species such as cows, horses, sheep, goats, pigs, and dogs. We believe that a better knowledge on the MaSC in these species will not only help to gain more insights into mammary gland (patho) physiology in veterinary medicine, but will also be of value for human medicine. Therefore, this review summarizes the current knowledge on stem cell isolation and characterization in different mammals of veterinary importance. PMID:23360296

  4. Chemoprevention of Radiation Induced Rat Mammary Neoplasms (United States)

    Huso, David L.


    Radiations encountered in space include protons and heavy ions such as iron as well as their secondaries. The relative biological effect (RBE) of these ions is not known, particularly at the doses and dose-rates expected for planetary missions. Neutrons, are not particularly relevant to space travel, but have been found experimentally to have an increase in their RBE with decreasing dose. If a similar trend of increasing RBE with decreasing dose is present for heavy ions and protons during irradiation in space, the small doses received during space travel could potentially have substantial carcinogenic risk. Clearly more investigation of the effects of heavy ions and protons is needed before accurate risk assessment for prolonged travel in space can be done. One means to mitigate the increased risk of cancer due to radiation exposure in space is by developing effective countermeasures that can reduce the incidence of tumor development. Tamoxifen has recently been shown to be an effective chemopreventive agent in both animal models and humans for the prevention of mammary tumors. Tamoxifen is a unique drug, with a highly specific mechanism of action affecting a specific radiation-sensitive population of epithelial cells in the mammary gland. In human studies, the annual incidence of a primary tumor in the contralateral breast of women with previous breast cancer is about 8 per 1000, making them an exceedingly high-risk group for the development of breast cancer. In this high risk group, treated with tamoxifen, daily, for 2 years, the incidence of a new primary tumor in the contralateral breast was approximately one third of that noted in the non-tamoxifen treatment group. Tamoxifen antagonizes the action of estrogen by competing for the nuclear receptor complex thereby altering the association of the receptor complex and nuclear binding sites. Its effects in reducing the development of breast cancer could be accomplished by controlling clinically undetectable

  5. Genomic and Phenomic Study of Mammary Pathogenic Escherichia coli (United States)

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


    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

  6. Conserved and variable: Understanding mammary stem cells across species. (United States)

    Rauner, Gat; Ledet, Melissa M; Van de Walle, Gerlinde R


    Postnatal mammary gland development requires the presence of mammary stem and progenitor cells (MaSC), which give rise to functional milk-secreting cells and regenerate the mammary epithelium with each cycle of lactation. These long-lived, tissue-resident MaSC are also targets for malignant transformation and may be cancer cells-of-origin. Consequently, MaSC are extensively researched in relation to their role and function in development, tissue regeneration, lactation, and breast cancer. The basic structure and function of the mammary gland are conserved among all mammalian species, from the most primitive to the most evolved. However, species vary greatly in their lactation strategies and mammary cancer incidence, making MaSC an interesting focus for comparative research. MaSC have been characterized in mice, to a lesser degree in humans, and to an even lesser degree in few additional mammals. They remain uncharacterized in most mammalian species, including "ancient" monotremes, marsupials, wild, and rare species, as well as in common and domestic species such as cats. Identification and comparison of MaSC across a large variety of species, particularly those with extreme lactational adaptations or low mammary cancer incidence, is expected to deepen our understanding of development and malignancy in the mammary gland. Here, we review the current status of MaSC characterization across species, and underline species variations in lactation and mammary cancer through which we may learn about the role of MaSC in these processes. © 2017 International Society for Advancement of Cytometry. © 2017 International Society for Advancement of Cytometry.

  7. Delivering the message: epimorphin and mammary epithelial morphogenesis☆


    Radisky, Derek C.; Hirai, Yohei; Bissell, Mina J.


    The mammary gland consists of a highly branched tubular epithelium surrounded by a complex mesenchymal stroma. Epimorphin is an extracellular protein that is expressed by mammary mesenchymal cells that directs epithelial morphogenesis. Depending upon the context of presentation – polar versus apolar – epimorphin can selectively direct two key processes of tubulogenesis: branching morphogenesis (processes involved in tubule initiation and extension) and luminal morphogenesis (required for enla...

  8. Mammary odor cues and pheromones: mammalian infant-directed communication about maternal state, mammae, and milk. (United States)

    Schaal, Benoist


    Neonatal mammals are exposed to an outstandingly powerful selective pressure at birth, and any mean to alleviate their localization effort and accelerate acceptance to orally grasp a nipple and ingest milk should have had advantageous consequences over evolutionary time. Thus, it is essential for females to display a biological interface structure that is sensorily conspicuous and executively easy for their newborns. Females' strategy to increase the conspicuousness of nipples could only exploit the newborns' most advanced and conserved sensory systems, touch and olfaction, and selection has accordingly shaped tactilely and olfactorily conspicuous mammary structures. This evolutionary modification has worked either by affecting structural features of mammaries or indirectly by affecting maternal behavioral propensities to create olfactory traces on them. These predictions are considered here in mammalian cases that have received empirical attention among marsupials, rodents, lagomorphs, ungulates, carnivores, and primates. It appears that broadcasting chemical cues and/or signals from the mammae is a pan-mammalian reproductive strategy to pilot neonatal arousal, motivation and attraction to the mother, provide assistance in localizing and orally grasping the mammae, and boost up learning. But the ways by which these chemical cues are produced and assembled on the mammae are both diverse between species and complex within species, offering an outstanding opportunity for comparative analyses in chemical communication. Copyright © 2010 Elsevier Inc. All rights reserved.

  9. Epstein–Barr Virus Infection of Mammary Epithelial Cells Promotes Malignant Transformation

    Directory of Open Access Journals (Sweden)

    Hai Hu


    Full Text Available Whether the human tumor virus, Epstein–Barr Virus (EBV, promotes breast cancer remains controversial and a potential mechanism has remained elusive. Here we show that EBV can infect primary mammary epithelial cells (MECs that express the receptor CD21. EBV infection leads to the expansion of early MEC progenitor cells with a stem cell phenotype, activates MET signaling and enforces a differentiation block. When MECs were implanted as xenografts, EBV infection cooperated with activated Ras and accelerated the formation of breast cancer. Infection in EBV-related tumors was of a latency type II pattern, similar to nasopharyngeal carcinoma (NPC. A human gene expression signature for MECs infected with EBV, termed EBVness, was associated with high grade, estrogen-receptor-negative status, p53 mutation and poor survival. In 11/33 EBVness-positive tumors, EBV-DNA was detected by fluorescent in situ hybridization for the viral LMP1 and BXLF2 genes. In an analysis of the TCGA breast cancer data EBVness correlated with the presence of the APOBEC mutational signature. We conclude that a contribution of EBV to breast cancer etiology is plausible, through a mechanism in which EBV infection predisposes mammary epithelial cells to malignant transformation, but is no longer required once malignant transformation has occurred.

  10. Mammary hypoplasia: not every breast can produce sufficient milk. (United States)

    Arbour, Megan W; Kessler, Julia Lange


    Breast milk is considered the optimal form of nutrition for newborn infants. Current recommendations are to breastfeed for 6 months. Not all women are able to breastfeed. Mammary hypoplasia is a primary cause of failed lactogenesis II, whereby the mother is unable to produce an adequate milk volume. Women with mammary hypoplasia often have normal hormone levels and innervation but lack sufficient glandular tissue to produce an adequate milk supply to sustain their infant. The etiology of this rare condition is unclear, although there are theories that refer to genetic predisposition and estrogenic environmental exposures in select agricultural environments. Women with mammary hypoplasia may not exhibit the typical breast changes associated with pregnancy and may fail to lactate postpartum. Breasts of women with mammary hypoplasia may be widely spaced (1.5 inches or greater), asymmetric, or tuberous in nature. Awareness of the history and clinical signs of mammary hypoplasia during the prenatal period and immediate postpartum increases the likelihood that women will receive the needed education and physical and emotional support and encouragement. Several medications and herbs demonstrate some efficacy in increasing breast milk production in women with mammary hypoplasia. © 2013 by the American College of Nurse-Midwives.

  11. Coagulogram of the 35 females dogs with mammary neoplasias

    Directory of Open Access Journals (Sweden)

    Cristina Rauen Ribas


    Full Text Available ABSTRACT. Ribas C.R., Dornbusch P.T., de Faria M.R., Cirio S.M. & Wouk A.F.P. de F. [Coagulogram of the 35 females dogs with mammary neoplasias.] Coagulograma de 35 cadelas com neoplasias mamárias. Revista Brasileira de Medicina Veterinária, 37(1:83-87, 2015. Departamento de Medicina Veteriná- ria, Universidade Federal do Paraná, Rua dos Funcionários 1540, Curitiba, PR, 80035-050, Brasil. E-mail: The mammary neoplasias are easily noticed by the owners, and are increasingly on the rise due to greater longevity of animals in recent years. So often cater to large number of female dogs in routine clinical medical oncology in small animals. Epidemiologically, the mammary neoplasias affecting mainly older dogs not spayed or neutered after several heats, with no racial predisposition. However, hardly possible to report laboratory findings directly or indirectly related to the neoplastic process. Therefore, the aim of this study was to analyze the coagulation of 36 dogs suffering from mammary cancer, diagnosed clinically and confirmed histopathologically. It was possible to identify changes such as decrease of TTPA (activated partial thromboplastin time, thrombocytosis, thrombocytopenia, disseminated intravascular coagulation (DIC. It was concluded that the alterations in coagulation of female dogs with mammary neoplasms were more significant in dogs suffering from mammary tumors in stage V.

  12. The role of tight junctions in mammary gland function. (United States)

    Stelwagen, Kerst; Singh, Kuljeet


    Tight junctions (TJ) are cellular structures that facilitate cell-cell communication and are important in maintaining the three-dimensional structure of epithelia. It is only during the last two decades that the molecular make-up of TJ is becoming unravelled, with two major transmembrane-spanning structural protein families, called occludin and claudins, being the true constituents of the TJ. These TJ proteins are linked via specific scaffolding proteins to the cell's cytoskeleton. In the mammary gland TJ between adjacent secretory epithelial cells are formed during lactogenesis and are instrumental in establishing and maintaining milk synthesis and secretion, whereas TJ integrity is compromised during mammary involution and also as result of mastitis and periods of mammary inflamation (including mastitis). They prevent the paracellular transport of ions and small molecules between the blood and milk compartments. Formation of intact TJ at the start of lactation is important for the establishment of the lactation. Conversely, loss of TJ integrity has been linked to reduced milk secretion and mammary function and increased paracellular transport of blood components into the milk and vice versa. In addition to acting as a paracellular barrier, the TJ is increasingly linked to playing an active role in intracellular signalling. This review focusses on the role of TJ in mammary function of the normal, non-malignant mammary gland, predominantly in ruminants, the major dairy producing species.

  13. Laser acceleration (United States)

    Tajima, T.; Nakajima, K.; Mourou, G.


    The fundamental idea of Laser Wakefield Acceleration (LWFA) is reviewed. An ultrafast intense laser pulse drives coherent wakefield with a relativistic amplitude robustly supported by the plasma. While the large amplitude of wakefields involves collective resonant oscillations of the eigenmode of the entire plasma electrons, the wake phase velocity ˜ c and ultrafastness of the laser pulse introduce the wake stability and rigidity. A large number of worldwide experiments show a rapid progress of this concept realization toward both the high-energy accelerator prospect and broad applications. The strong interest in this has been spurring and stimulating novel laser technologies, including the Chirped Pulse Amplification, the Thin Film Compression, the Coherent Amplification Network, and the Relativistic Mirror Compression. These in turn have created a conglomerate of novel science and technology with LWFA to form a new genre of high field science with many parameters of merit in this field increasing exponentially lately. This science has triggered a number of worldwide research centers and initiatives. Associated physics of ion acceleration, X-ray generation, and astrophysical processes of ultrahigh energy cosmic rays are reviewed. Applications such as X-ray free electron laser, cancer therapy, and radioisotope production etc. are considered. A new avenue of LWFA using nanomaterials is also emerging.

  14. Accelerators and the Accelerator Community

    Energy Technology Data Exchange (ETDEWEB)

    Malamud, Ernest; Sessler, Andrew


    In this paper, standing back--looking from afar--and adopting a historical perspective, the field of accelerator science is examined. How it grew, what are the forces that made it what it is, where it is now, and what it is likely to be in the future are the subjects explored. Clearly, a great deal of personal opinion is invoked in this process.

  15. accelerating cavity

    CERN Multimedia

    On the inside of the cavity there is a layer of niobium. Operating at 4.2 degrees above absolute zero, the niobium is superconducting and carries an accelerating field of 6 million volts per metre with negligible losses. Each cavity has a surface of 6 m2. The niobium layer is only 1.2 microns thick, ten times thinner than a hair. Such a large area had never been coated to such a high accuracy. A speck of dust could ruin the performance of the whole cavity so the work had to be done in an extremely clean environment.

  16. Metabotropic glutamate receptor 1 disrupts mammary acinar architecture and initiates malignant transformation of mammary epithelial cells. (United States)

    Teh, Jessica L F; Shah, Raj; La Cava, Stephanie; Dolfi, Sonia C; Mehta, Madhura S; Kongara, Sameera; Price, Sandy; Ganesan, Shridar; Reuhl, Kenneth R; Hirshfield, Kim M; Karantza, Vassiliki; Chen, Suzie


    Metabotropic glutamate receptor 1 (mGluR1/Grm1) is a member of the G-protein-coupled receptor superfamily, which was once thought to only participate in synaptic transmission and neuronal excitability, but has more recently been implicated in non-neuronal tissue functions. We previously described the oncogenic properties of Grm1 in cultured melanocytes in vitro and in spontaneous melanoma development with 100 % penetrance in vivo. Aberrant mGluR1 expression was detected in 60-80 % of human melanoma cell lines and biopsy samples. As most human cancers are of epithelial origin, we utilized immortalized mouse mammary epithelial cells (iMMECs) as a model system to study the transformative properties of Grm1. We introduced Grm1 into iMMECs and isolated several stable mGluR1-expressing clones. Phenotypic alterations in mammary acinar architecture were assessed using three-dimensional morphogenesis assays. We found that mGluR1-expressing iMMECs exhibited delayed lumen formation in association with decreased central acinar cell death, disrupted cell polarity, and a dramatic increase in the activation of the mitogen-activated protein kinase pathway. Orthotopic implantation of mGluR1-expressing iMMEC clones into mammary fat pads of immunodeficient nude mice resulted in mammary tumor formation in vivo. Persistent mGluR1 expression was required for the maintenance of the tumorigenic phenotypes in vitro and in vivo, as demonstrated by an inducible Grm1-silencing RNA system. Furthermore, mGluR1 was found be expressed in human breast cancer cell lines and breast tumor biopsies. Elevated levels of extracellular glutamate were observed in mGluR1-expressing breast cancer cell lines and concurrent treatment of MCF7 xenografts with glutamate release inhibitor, riluzole, and an AKT inhibitor led to suppression of tumor progression. Our results are likely relevant to human breast cancer, highlighting a putative role of mGluR1 in the pathophysiology of breast cancer and the potential

  17. The Role of SnoN and Ski in Mammary Epithelial Cell Transformation

    National Research Council Canada - National Science Library

    Pan, Deng


    .... Higher level of Ski/SnoN is found in transformed mammary epithelial cells. Ski/SnoN might play a role in regulation of the transformation of mammary epithelial cell by antagonizing TGF signaling pathway...

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

    National Research Council Canada - National Science Library

    Nagy, Tamas


    ...) deletion in mammary-specific polyoma middle-T transgenic mice. We monitored mammary carcinogenesis in positive control (FAKFlox/Flox; MMTV-PyVT) and target (FAKFlox/Flox; MMTV-Cre; MMTV-PyVT) females...

  19. Mechanisms Underlying the Very High Susceptibility of the Immature Mammary Gland to Carcinogenic Initiation

    National Research Council Canada - National Science Library

    Gould, Michael


    The overall goal of this project was to explore the toxic effects of physical and chemical carcinogens on the immature mammary gland as compared to the effects on the young adult mammary gland using a rat model. We have: I...

  20. The Role of Phosphatidylinositol 3' -OH Kinase Signaling in Mammary Tumorigenesis

    National Research Council Canada - National Science Library

    Hutchinson, John


    ...) and its downstream targets such as the Akt kinase in the induction of mammary tumors. To assess the role of Akt in mammary development and tumorigenesis, we have generated transgenic mice that express an activated Akt (Akt-DD...

  1. The Role of Phosphatidylinositol 3' -OH Kinase Signaling in Mammary Tumorigenesis

    National Research Council Canada - National Science Library

    Hutchinson, John


    ...) and its downstream target Akt kinase in the induction of mammary tumors. To assess the role of Akt in mammary development and tumorigenesis, we generated transgenic mice that express an activated Akt (Akt-DD...

  2. ErbB3 drives mammary epithelial survival and differentiation during pregnancy and lactation

    National Research Council Canada - National Science Library

    Michelle M Williams; David B Vaught; Meghan Morrison Joly; Donna J Hicks; Violeta Sanchez; Philip Owens; Bushra Rahman; David L Elion; Justin M Balko; Rebecca S Cook


    ...) signaling, contributes to lactogenic expansion of the mammary gland. Methods We assessed mRNA expression levels by expression microarray of mouse mammary glands harvested throughout pregnancy and lactation...

  3. Mammary remodeling in primiparous and multiparous dairy goats during lactation. (United States)

    Safayi, S; Theil, P K; Elbrønd, V S; Hou, L; Engbaek, M; Nørgaard, J V; Sejrsen, K; Nielsen, M O


    Milk production is generally lower but lactation persistency higher in primiparous (PP) than in multiparous (MP) goats. This may be related to differences in development and maintenance of mammary gland function, but the underlying mechanisms are not well understood. The present study aimed to elucidate whether differences in lactational performance between PP and MP mammary glands are related to the time course of development and maintenance, not only of the mammary epithelial cell (MEC) population, but also of the mammary vasculature that sustains synthetic activity. Mammary biopsies were obtained from both mammary glands of 3 PP and 6 MP (>or=2 parity) dairy goats at parturition (d 1), d 10, 60, and 180 of lactation. Gene transcription relating to MEC turnover and vascular function was quantified by real-time reverse transcription-PCR, mammary morphology was characterized (quantitative histology), and cell turnover was determined (terminal deoxynucleotidyl transferase dUTP nick end labeling assay and Ki-67). Primiparous glands showed higher expression for the genes involved in angiogenesis; namely, vascular endothelial growth factor receptor 2, and angiopoietin 1 and 2 and their receptor, a few days after parturition (d 10). Primiparous glands also had higher rates of MEC proliferation in early lactation. It therefore appears that initiation of lactation is associated with development and growth of the mammary gland into early lactation, which continues for a longer period in PP compared with MP glands. In addition, MEC survival was found to be higher in PP glands throughout lactation, and MEC in PP glands underwent more extensive differentiation. This could explain the reported flatter lactation curve and higher lactation persistency in PP glands. Although some of the genes included in this study were differentially expressed in PP and MP glands during the course of lactation, it was not possible to identify any specific genomic factor(s) that could account for

  4. [Mammary carcinoma in a patient with hyperprolactinemia]. (United States)

    Gola, M; Papi, G; Tavernari, V; Pesenti, M; Ficarra, G; Velardo, A


    In 1990, a 50 year-old man was referred to us for hyperprolactinemia. At 37 years of age the patient had undergone left mastectomy, for a histologically confirmed gynecomastia and, in 1989, he had undergone pituitary adenomectomy, for a PRL secreting macroadenoma (PRL = 3520 ng/ml). Persistently high PRL plasma levels (PRL = 550 ng/ml) showed an incomplete surgical removal of the adenoma and as a consequence, radiotherapy of the pituitary area was performed in 1990. When the patient referred to us, PRL plasma levels were still pathologic and medical therapy with bromocriptine was started. A year later a replacement therapy with cortisone, testosterone, L-thyroxine, was commenced, as the patient presented a post-radiotherapy hypopituitarism. Since the treatment with bromocriptine was unsuccessful, the drug was replaced with cabergoline, but not even the latter was able to normalize PRL plasma levels. In 1996, a nodule of 3 cm in diameter was discovered under his right mammary areola. The nodule biopsy showed a grade II infiltrating ductal breast carcinoma positive to the estrogen and progesterone receptors analysis. A right total mastectomy was performed and the diagnosis was confirmed through histological examination. A case of gynecomastia and breast cancer in a male patient who had been exposed to high PRL plasma levels for several years is reported. In this patient, both elevated PRL plasma levels and a relative hyperestrogenic state may have contributed to originate breast cancer.

  5. Epithelioid mammary myofibroblastoma mimicking invasive lobular carcinoma. (United States)

    Arafah, Maria A; Ginter, Paula S; D'Alfonso, Timothy M; Hoda, Syed A


    A case of a 53-year-old woman with the epithelioid variant of mammary myofibroblastoma, which was initially misinterpreted as invasive lobular carcinoma, is presented. A needle core biopsy of the 1.6 cm mass showed interlacing bundles of epithelioid myofibroblasts amid dense fibrous tissue associated with lobular carcinoma in situ of the classical type. Most epithelioid cells showed nuclear atypia, and a few exhibited signet-ring cytology. Immunoreactivity for estrogen and progesterone receptors further compounded the deception, and the neoplasm was misinterpreted as invasive lobular carcinoma. Excisional biopsy showed a circumscribed stromal tumor with foci suspicious for invasive lobular carcinoma. The latter was excluded by cytokeratin negativity throughout the tumor. The overall histopathological appearance and immunostaining pattern was confirmatory of myofibroblastoma. This case report emphasizes the potential for mistaking epithelioid myofibroblastoma for invasive lobular carcinoma--particularly in the setting of limited sampling, hormone-receptor immunoreactivity of the lesional cells, and synchronous lobular carcinoma in situ. © The Author(s) 2015.

  6. Mammary analogue secretory carcinoma mimicking salivary adenoma. (United States)

    Williams, Lindsay; Chiosea, Simion I


    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor characterized by ETV6 translocation. It appears that prior studies have identified MASC by reviewing salivary gland carcinomas, such as acinic cell carcinoma and adenocarcinoma, not otherwise specified. To address the possibility of MASC mimicking benign salivary neoplasms we reviewed 12 salivary gland (cyst)adenomas diagnosed prior to the discovery of MASC. One encapsulated (cyst)adenoma of the parotid gland demonstrated features of MASC. The diagnosis was confirmed by fluorescence in situ hybridization with an ETV6 break-apart probe. An unusual complex pattern of ETV6 rearrangement with duplication of the telomeric/distal ETV6 probe was identified. This case illustrates that MASC may mimic salivary (cyst)adenomas. To more accurately assess true clinical and morphologic spectrum of MASC, future studies may have to include review of salivary (cyst)adenomas. The differential diagnosis of MASC may have to be expanded to include cases resembling salivary (cyst)adenomas.

  7. Mammary field cancerization: molecular evidence and clinical importance. (United States)

    Heaphy, Christopher M; Griffith, Jeffrey K; Bisoffi, Marco


    The term "field cancerization" originally denoted the presence of histologically abnormal tissue/cells surrounding primary tumors of the head and neck. Similar concepts with different and continuously changing definitions have been used for other types of tumors including breast adenocarcinoma, where field cancerization presently denotes the occurrence of molecular alterations in histologically normal tissues surrounding areas of overt cancer. Human mammary tissue morphology lends itself to the proposed concepts of field cancerization, which may include the gradual accumulation of genetic and other aberrations in stationary epithelial cells with intact morphology, or the spread of histologically normal yet genetically aberrant epithelial cells within mammary tissue. In this report, we review published molecular genetic, epigenetic, and gene expressional data in support of field cancerization in human mammary tissues. We then discuss the clinical implications of mammary field cancerization, including its source for potential biomarkers with diagnostic/prognostic potential, and its relationship to surgical margins and disease recurrence. We conclude with a future outlook on further research on mammary field cancerization addressing experimental methods, as well as the development of possible models and integrated approaches to gain a better understanding of the underlying mechanisms with the ultimate goal of developing clinical applications.

  8. Internal mammary sentinel lymph node biopsy: abandon or persist?

    Directory of Open Access Journals (Sweden)

    Qiu PF


    Full Text Available Peng-Fei Qiu, Yan-Bing Liu, Yong-Sheng Wang Breast Cancer Center, Shandong Cancer Hospital and Institute, Jinan, Shandong, People’s Republic of China Abstract: Although the 2009 American Joint Committee on Cancer incorporated the internal mammary sentinel lymph node biopsy (IM-SLNB concept, there has been little change in surgical practice patterns due to the low visualization rate of internal mammary sentinel lymph nodes with the traditional injection technique. Meanwhile, as internal mammary lymph nodes (IMLN metastases are mostly found concomitantly with axillary lymph nodes (ALN metastases, previous IM-SLNB clinical trials fail to evaluate the status of IMLN in patients who are really in need (only in clinically ALN negative patients. Our modified injection technique (periareolar intraparenchymal, high volume, and ultrasonographic guidance significantly improved the visualization rate of internal mammary sentinel lymph nodes, making the routine IM-SLNB possible in daily practice. IM-SLNB could provide individual minimally invasive staging, prognosis, and decision-making for breast cancer patients, especially for patients with clinically positive ALN. Moreover, IMLN radiotherapy should be tailored and balanced between the potential benefit and toxicity, and IM-SLNB-guided IMLN radiotherapy could achieve this goal. In the era of effective adjuvant therapy, within the changing treatment approach – more systemic therapy, less loco-regional therapy – clinicians should deliberate the application of regional IMLN therapy. Keywords: breast cancer, internal mammary lymph node, axillary lymph node, sentinel lymph node biopsy 

  9. File list: Unc.Brs.05.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. File list: ALL.Brs.05.AllAg.Mammary_stem_cells [Chip-atlas[Archive

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  13. File list: Oth.Brs.10.AllAg.Mammary_stem_cells [Chip-atlas[Archive

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    Full Text Available Oth.Brs.10.AllAg.Mammary_stem_cells mm9 TFs and others Breast Mammary stem cells ...

  14. File list: Pol.Brs.10.AllAg.Mammary_stem_cells [Chip-atlas[Archive

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    Full Text Available Pol.Brs.10.AllAg.Mammary_stem_cells mm9 RNA polymerase Breast Mammary stem cells ...

  15. File list: Unc.Brs.50.AllAg.Mammary_stem_cells [Chip-atlas[Archive

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  16. File list: DNS.Brs.20.AllAg.Mammary_stem_cells [Chip-atlas[Archive

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  17. File list: Oth.Brs.05.AllAg.Mammary_stem_cells [Chip-atlas[Archive

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  19. File list: Unc.Brs.05.AllAg.Mammary_glands [Chip-atlas[Archive

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  20. File list: Oth.Brs.50.AllAg.Mammary_glands [Chip-atlas[Archive

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  2. File list: Pol.Brs.10.AllAg.Mammary_cells [Chip-atlas[Archive

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  3. Mammary carcinogenesis in rats: basic facts and recent results in Brookhaven

    Energy Technology Data Exchange (ETDEWEB)

    Shellabarger, C.J.; Stone, J.P.; Holtzman, s.


    Some research results from experiments investigating neutron-induced mammary carcinogenesis in rats are presented. The additive effects of neutrons and 3-methylcholanthrene on mammary adenocarcinoma were determined. Synergism between diethylstilbestrol and neutrons was likewise studied. Differences in mammary neoplastic response between strains of laboratory rats was also investigated. (ACR)

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  5. File list: His.Brs.10.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

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  6. File list: His.Brs.05.AllAg.Mammary_stem_cells [Chip-atlas[Archive

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  7. File list: Pol.Brs.50.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

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  8. File list: His.Brs.20.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

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  9. File list: Pol.Brs.10.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

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  10. File list: DNS.Brs.20.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

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  11. File list: His.Brs.05.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

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  12. File list: Oth.Brs.20.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

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  13. File list: Oth.Brs.10.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

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  14. File list: DNS.Brs.10.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

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  15. File list: His.Brs.50.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

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  16. File list: Unc.Brs.05.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

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  17. File list: ALL.Brs.50.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

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  18. File list: ALL.Brs.05.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

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  19. File list: Pol.Brs.20.AllAg.Mammary_cells [Chip-atlas[Archive

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    Full Text Available Pol.Brs.20.AllAg.Mammary_cells mm9 RNA polymerase Breast Mammary cells SRX852566,SR...X852567,SRX187510,SRX187515 ...

  20. File list: Oth.Brs.05.AllAg.Mammary_cells [Chip-atlas[Archive

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  1. File list: InP.Brs.20.AllAg.Mammary_cells [Chip-atlas[Archive

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  2. File list: Pol.Brs.05.AllAg.Mammary_cells [Chip-atlas[Archive

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  3. File list: ALL.Brs.20.AllAg.Mammary_cells [Chip-atlas[Archive

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  4. File list: ALL.Brs.10.AllAg.Mammary_cells [Chip-atlas[Archive

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  5. File list: InP.Brs.50.AllAg.Mammary_cells [Chip-atlas[Archive

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  6. File list: InP.Brs.05.AllAg.Mammary_cells [Chip-atlas[Archive

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  7. File list: ALL.Brs.05.AllAg.Mammary_glands [Chip-atlas[Archive

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  8. File list: ALL.Brs.20.AllAg.Mammary_tumor [Chip-atlas[Archive

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  9. File list: Oth.Brs.10.AllAg.Mammary_cells [Chip-atlas[Archive

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  10. File list: His.Brs.20.AllAg.Mammary_cells [Chip-atlas[Archive

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  11. File list: Oth.Brs.20.AllAg.Mammary_cells [Chip-atlas[Archive

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  12. File list: Pol.Brs.50.AllAg.Mammary_glands [Chip-atlas[Archive

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  13. File list: His.Brs.50.AllAg.Mammary_cells [Chip-atlas[Archive

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  14. File list: His.Brs.05.AllAg.Mammary_cells [Chip-atlas[Archive

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  15. File list: Unc.Brs.10.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

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  16. File list: Unc.Brs.20.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

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  17. File list: Pol.Brs.50.AllAg.Mammary_stem_cells [Chip-atlas[Archive

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  18. File list: Unc.Brs.10.AllAg.Mammary_stem_cells [Chip-atlas[Archive

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  19. File list: His.Brs.20.AllAg.Mammary_stem_cells [Chip-atlas[Archive

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  20. File list: His.Brs.10.AllAg.Mammary_stem_cells [Chip-atlas[Archive

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  1. File list: His.Brs.50.AllAg.Mammary_stem_cells [Chip-atlas[Archive

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  2. File list: DNS.Brs.05.AllAg.Mammary_stem_cells [Chip-atlas[Archive

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  3. File list: ALL.Brs.50.AllAg.Mammary_cells [Chip-atlas[Archive

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  4. File list: His.Brs.10.AllAg.Mammary_cells [Chip-atlas[Archive

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  5. File list: His.Brs.05.AllAg.Mammary_glands [Chip-atlas[Archive

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  6. File list: Oth.Brs.05.AllAg.Mammary_glands [Chip-atlas[Archive

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  7. File list: Unc.Brs.50.AllAg.Mammary_glands [Chip-atlas[Archive

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  8. File list: Pol.Brs.10.AllAg.Mammary_glands [Chip-atlas[Archive

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  9. File list: Unc.Brs.20.AllAg.Mammary_glands [Chip-atlas[Archive

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  10. File list: InP.Brs.10.AllAg.Mammary_cells [Chip-atlas[Archive

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  11. File list: InP.Brs.05.AllAg.Mammary_glands [Chip-atlas[Archive

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  12. File list: Unc.Brs.10.AllAg.Mammary_glands [Chip-atlas[Archive

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  13. File list: InP.Brs.20.AllAg.Mammary_glands [Chip-atlas[Archive

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  14. File list: ALL.Brs.20.AllAg.Mammary_glands [Chip-atlas[Archive

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  15. File list: InP.Brs.10.AllAg.Mammary_glands [Chip-atlas[Archive

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  16. File list: Pol.Brs.05.AllAg.Mammary_glands [Chip-atlas[Archive

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  17. File list: Oth.Brs.05.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

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    Full Text Available Oth.Brs.05.AllAg.Mammary_epithelial_cells mm9 TFs and others Breast Mammary epithel...ial cells SRX424872,SRX330635,SRX330636 ...

  18. File list: ALL.Brs.10.AllAg.Mammary_tumor [Chip-atlas[Archive

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  19. File list: Pol.Brs.50.AllAg.Mammary_cells [Chip-atlas[Archive

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  20. File list: ALL.Brs.10.AllAg.Mammary_glands [Chip-atlas[Archive

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  1. File list: Oth.Brs.10.AllAg.Mammary_glands [Chip-atlas[Archive

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  11. FOXC1 is enriched in the mammary luminal progenitor population, but is not necessary for mouse mammary ductal morphogenesis. (United States)

    Sizemore, Gina M; Sizemore, Steven T; Pal, Bhupinder; Booth, Christine N; Seachrist, Darcie D; Abdul-Karim, Fadi W; Kume, Tsutomu; Keri, Ruth A


    Expression of FOXC1, a forkhead box transcription factor, correlates with the human basal-like breast cancer (BLBC) subtype, and functional analyses have revealed its importance for in vitro invasiveness of BLBC cells. Women diagnosed with this breast tumor subtype have a poorer outcome because of the lack of targeted therapies; thus, continued investigation of factors driving these tumors is critical to uncover novel therapeutic targets. Several processes that dictate normal mammary morphogenesis parallel cancer progression, and enforced expression of FOXC1 can induce a progenitor state in more-differentiated mammary epithelial cells. Consequently, evaluating how FOXC1 functions in the normal gland is critical to further understand BLBC biology. Although FOXC1 is well known to control normal development of a number of tissues, its role in the mammary gland has not yet been investigated. Herein, we describe FOXC1 expression patterning in the normal breast, where it is localized to the basal/myoepithelium, suggesting that FOXC1 would be required for normal development. However, mammary glands lacking Foxc1 have no overt defect in ductal outgrowth, alveologenesis, or lineage specification. Of significant interest, we found that expression of FOXC1 is enriched in the normal luminal progenitor population, which is the postulated cell of origin of BLBC. These results indicate that FOXC1 is unnecessary for mammary morphogenesis and that its role in BLBC likely involves processes that are unrelated to cell lineage specification.

  12. Mammary Gland Reprogramming: Metalloproteinases Couple Form with Function (United States)

    Khokha, Rama; Werb, Zena


    The adult mammary structure provides for the rapid growth, development, and immunological protection of the live-born young of mammals through its production of milk. The dynamic remodeling of the branched epithelial structure of the mammary gland in response to physiological stimuli that allow its programmed branching morphogenesis at puberty, cyclical turnover during the reproductive cycle, differentiation into a secretory organ at parturition, postlactational involution, and ultimately, regression with age is critical for these processes. Extracellular metalloproteinases are essential for the remodeling programs that operate in the tissue microenvironment at the interface of the epithelium and the stroma, coupling form with function. Deregulated proteolytic activity drives the transition of a physiological mammary microenvironment into a tumor microenvironment, facilitating malignant transformation. PMID:21106646

  13. Mammary mechanisms for lactoferrin: interactions with IGFBP-3.

    Directory of Open Access Journals (Sweden)

    Baumrucker C.R.


    Full Text Available Lactoferrin (Lf is an iron-binding protein found in high concentrations in mammary secretions but synthesized by many tissues. Bovine mammary tissue secretes microg/ml mass of Lf in milk, but during involution and prepartum periods, 20-80 mg per ml concentrations may be observed. While a number of functions have been ascribed to lactoterrin, only the antimicrobial and lymphocyte interactions have compelling experimental evidence of support. We report a new finding that lactoferrin binds to insulin-like growth factor binding protein-3 (IGFBP-3 and not to other mammary secreted IGFBPs (IGFBP-2, -4. and -5. Furthermore, bovine Lf(bLf is found associated with membranes of mammary cells. We demonstrate that bovine Lf competes with IGF for binding to IGFBP-3 with ED50 competition of 3 microg per ml and displacement of 1 mg per ml to monomeric bLf. The tetrameric form that is favored by high concentrations of Lf and calcium, does not appear to bind IGFBP-3. Both IGFBP-3 and Lf have nuclear localization sequences that are reported to he key components of nuclear localization of proteins. We demonstrate that extracellular IGFBP-3 binds to membrane Lf and that Lf is the key to the entry of IGFBP-3 to mammary cellular nucleus. Additionally, we have shown that the internalization of Lf requires the presence of retinoids that also induces both IGFBP-3 and Lf synthesis in primary cultures of bovine mammary epithelial cells. We hypothesize a new role for Lf in the regulation and integration into the IGF System.

  14. The mammary gland in domestic ruminants: a systems biology perspective. (United States)

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


    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. Malignant mammary tumor in female dogs: environmental contaminants

    Directory of Open Access Journals (Sweden)

    Bissacot Denise Z


    Full Text Available Abstract Mammary tumors of female dogs have greatly increased in recent years, thus demanding rapid diagnosis and effective treatment in order to determine the animal survival. There is considerable scientific interest in the possible role of environmental contaminants in the etiology of mammary tumors, specifically in relation to synthetic chemical substances released into the environment to which living beings are either directly or indirectly exposed. In this study, the presence of pyrethroid insecticide was observed in adjacent adipose tissue of canine mammary tumor. High Precision Liquid Chromatography - HPLC was adapted to detect and identify environmental contaminants in adipose tissue adjacent to malignant mammary tumor in nine female dogs, without predilection for breed or age. After surgery, masses were carefully examined for malignant neoplastic lesions. Five grams of adipose tissue adjacent to the tumor were collected to detect of environmental contaminants. The identified pyrethroids were allethrin, cyhalothrin, cypermethrin, deltamethrin and tetramethrin, with a contamination level of 33.3%. Histopathology demonstrated six female dogs (66.7% as having complex carcinoma and three (33.3% with simple carcinoma. From these tumors, seven (77.8% presented aggressiveness degree III and two (22.2% degree I. Five tumors were positive for estrogen receptors in immunohistochemical analysis. The contamination level was observed in more aggressive tumors. This was the first report in which the level of environmental contaminants could be detected in adipose tissue of female dogs with malignant mammary tumor, by HPLC. Results suggest the possible involvement of pyrethroid in the canine mammary tumor carcinogenesis. Hence, the dog may be used as a sentinel animal for human breast cancer, since human beings share the same environment and basically have the same eating habits.

  16. Vulnerability of Normal Human Mammary Epithelial Cells to Oncogenic Transformation (United States)


    escape senescence and acquire genomic changes. Nature 2001;409:633–7. 10. Olsen CL, Gardie B, Yaswen P, Stampfer MR. Raf-1- induced growth arrest in...p16INK4a. Cell 88:593–602. 10. Olsen CL, Gardie B, Yaswen P, Stampfer MR (2002) Raf-1-induced growth arrest in human mammary epithelial cells is p16...Cycle 3, 244–246. Olsen CL, Gardie B, Yaswen P, Stampfer MR (2002) Raf-1-induced growth arrest in human mammary epithelial cells is p16-independent and

  17. Establishment and characterization of eight feline mammary adenocarcinoma cell lines. (United States)

    Uyama, Rina; Hong, Sung-Hyeok; Nakagawa, Takayuki; Yazawa, Mitsuhiro; Kadosawa, Tsuyoshi; Mochizuki, Manabu; Tsujimoto, Hajime; Nishimura, Ryohei; Sasaki, Nobuo


    Eight new feline mammary adenocarcinoma cell lines derived from either primary or metastatic lesions were established. The morphology of all the cell lines was epithelioid and round to spindle in shape, with cell growth occurring in a monolayer fashion. On immunohistochemistry, these cells reacted with anti-keratin and anti-vimentin antisera. The doubling time of these cells was between 19 and 54 hr. Tumor masses were developed in nude mice by subcutaneous inoculation of the cells that were histologically identical to their original mammary tumor lesions. Telomerase activities measured using the telomeric repeat amplification protocol assay revealed high telemetric activity in all of the cells.

  18. Large mammary hamartoma with focal invasive ductal carcinoma

    Directory of Open Access Journals (Sweden)

    Pervatikar Suneet


    Full Text Available Mammary hamartomas are uncommon benign lesions rarely associated with malignancy. We report a case of a 25-year-old female patient presenting with a lump in the left breast. Fine needle aspiration cytology showed features of invasive ductal carcinoma along with normal benign glands that were mistaken for normal breast tissue. However, the mastectomy specimen revealed the malignant mass within a larger hamartomatous mass. Mammary hamartomas are benign lesions but, on exceedingly rare occasions, they may be involved by incidental, coexisting carcinoma, as illustrated in this case report.

  19. NMR characteristics of rat mammary tumors

    Energy Technology Data Exchange (ETDEWEB)

    Osbakken, M.; Kreider, J.; Taczanowsky, P.


    12 rats were injected intradermally with 13762A rat mammary adenocarcinoma (1 x 10/sup 6/ cells). 3 rats died before completion of the study and 2 rat had tumor regression; the first 3 were excluded from data analysis. NMR imaging with a 1.5K gauss resistive magnet at 2, 3, 4, and 5 weeks after injection demonstrated increasing tumor mass. Saturation recovery (SR), inversion recovery (IR), and spin echo (SE) pulse sequence images and T/sub 1/ calculation were done for tumor characterization. (Tumor size was too small to identify at 2 weeks.) 3 rats were sacrificed after the last 3 imaging periods for histological studies, done to distinguish solid tumor mass from necrosis. Planimetry of tumor areas showed that as tumors grew in size, the ratio of necrotic area to area of solid tumor increased (week 3 = .3 +- .11; week 4 = .45 +- .07; week 5 = .51 +- 05); simultaneous calculated T/sub 1/ values also increased (week 3 = .35 +- .15; week 4 = .45 +- .06; week 5 = .42 +- 03). Qualitative NMR image T/sub 1/ values also increased as evidenced by progression of SR and IR tumor image intensity from very bright compared to the rest of the body at week 3 to less intense than other structures at week 5. These findings indicate that change in T/sub 1/ may be secondary to the pathophysiological change in the tumor (the increasing in necrosis, associated with increased free water). Thus, the range of T/sub 1/ values obtained in tumors in this study (and in previous studies) may be due to change in tumor physiology and anatomy. Careful correlation of histological with NMR data may allow ultimate use of NMR relaxation characteristics for determination of the physiological state of tumors.

  20. Radiogenic neoplasia in thyroid and mammary clonogens

    Energy Technology Data Exchange (ETDEWEB)

    Clifton, K.H.


    We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. Previous results indicated that these clonogens are the precursor cells of radiogenic cancer, and that initiation, is common event at the clonegenic cell level. Detailed information on the physiologic control of clonogen proliferation, differentiation, and total numbers is thus essential to an understanding of the carcinogenic process. We report here studies on investigations on the relationships between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamus-pituitary feedback axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH-(thyrotropin-) responsive sub- population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and a large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cell interactions during the neoplastic process.

  1. Cytopathologic features of mammary analogue secretory carcinoma. (United States)

    Bishop, Justin A; Yonescu, Raluca; Batista, Denise A S; Westra, William H; Ali, Syed Z


    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland neoplasm that is defined by ETV6-NTRK3 gene fusion. To the best of the authors' knowledge, only rare case reports of the cytopathologic features of MASC have been published to date. A wide variety of archival salivary gland tumors were tested for ETV6 translocation by break-apart fluorescent in situ hybridization. Positive cases with preoperative fine-needle aspiration (FNA) specimens or intraoperative touch preparations were retrieved from the archives of The Johns Hopkins Hospital. All smears were reviewed and the cytologic characteristics were described. Five cases of MASC with cytopathologic material (4 FNA specimens and 1 touch preparation) were identified. The cases occurred in 3 men and 2 women ranging in age from 21 years to 78 years (mean, 52 years). On the cytologic smears, the MASCs were variably cellular and exhibited 2 different architectural patterns: 1) intact tissue fragments with isomorphic cells arranged in a sheet-like or papillary configuration; and 2) dispersed and dissociated cells with a mostly "histiocyte-like" appearance with large cells containing abundant vacuolated cytoplasm. No matrix tissue or stromal spindled cells were present. The cells did not display acinic differentiation in the form of cytoplasmic zymogen granules. In each case, the preoperative FNA correctly identified a neoplasm, and the most frequent diagnostic considerations were acinic cell carcinoma, mucoepidermoid carcinoma, and pleomorphic adenoma. MASC is a newly described salivary gland tumor that should be considered in the differential diagnosis of low-grade salivary gland neoplasms. Its cytologic features overlap considerably with those of other tumors, especially acinic cell carcinoma and mucoepidermoid carcinoma. Copyright © 2013 American Cancer Society.

  2. Technical note: Measurement of mammary plasma flow in sows by downstream dilution of mammary vein infused para-aminohippuric acid

    DEFF Research Database (Denmark)

    Larsen, Uffe Krogh; Storm, Adam Christian; Theil, Peter Kappel


    catheter was surgically implanted in the femoral artery, and another 2 were inserted in the right cranial mammary vein of 8 second- and third-parity sows on d 76 ± 2 SEM of gestation. On the 3rd and 17th days in milk, arterial and venous blood samples were drawn in hourly intervals from 0.5 h before until...... 6.5 h after feeding. The MPF in the right cranial mammary vein was measured by downstream dilution of infused pAH (3.0 mmol/h). Total MPF-pAH was calculated assuming that the measured flow constituted the flow from 5 out of 14 suckled glands on the basis of the anatomical structure of the mammary...

  3. Ghrelin is expressed in the pregnant mammary glands of dairy goats and promotes the cell proliferation of mammary epithelial cells. (United States)

    Zhang, Wenlong; Zhang, Zelin; Chen, Jinxuan; Tong, Dewen


    Little is known about ghrelin's effects on cell proliferation in pregnant mammary epithelial cells (MECs) even though it is known 4 to be a mitogen for a variety of other cell types. The objectives of this study were to evaluate the expression and localization of ghrelin and its functional receptor, GHSR-1a, in the mammary glands of dairy goats during pregnancy and to investigate the direct role of ghrelin in cell proliferation of primary cultured MECs. Compared to the early stage (days 30) of pregnancy, the abundance of transcripts and protein of ghrelin and GHSR-1a were significantly greater in mid- and late-phases (between days 90 and days 120) of pregnancy (p < 0.05). Immunohistochemistry analysis showed that ghrelin and GHSR-1a were predominantly localized in the alveolar and ductal mammary epithelial cells at various stages of pregnancy. In our in vitro experiments, ghrelin induced a dose- and time- dependent promotory effect on cell proliferation of MECs. At the dose of 103 pg/mL treatment 24 h, ghrelin augmented the expression of proliferation-related peptides (PCNA and cyclin B1). Furthermore, ghrelin promoted the expression of prolactin (PRL) and GHSR-1a in cultured MECs. Additionally, the the stimulatory effects of ghrelin were blocked by D-Lys3-GHRP6, a selective antagonist of GHSR-1a. As the temporal changes in ghrelin and GHSR-1a expression in pregnant goat mammary glands coincided with the mammary growth and development during the pregnancy, activation of GHSR-1a signal transduction pathways by ghrelin may play a direct role in the regulation of mammary growth in dairy goats. Copyright © 2018. Published by Elsevier Inc.

  4. Clinical Significance of Internal Mammary Lymph Node Biopsy during Microsurgical Breast Reconstruction: Review of 264 Cases. (United States)

    Wright, Eric J; Momeni, Arash; Kraneburg, Ursula M; Otake, Leo R; Echo, Anthony; Lee, Tim; Buchanan, Edward P; Lee, Gordon K


    Despite the knowledge of alternate lymphatic draining patterns of the breast, routine evaluation of the internal mammary lymph node basin is still not considered standard of care. The advent of microsurgical breast reconstruction using the internal mammary vessels as recipients, however, has allowed sampling of internal mammary lymph nodes with technical ease, thus revisiting their role in breast cancer management. In the present study, the authors reviewed their experience with this practice. A retrospective analysis of patients who underwent internal mammary lymph node biopsy at the time of autologous breast reconstruction using the internal mammary vessels between 2004 and 2012 was performed. Parameters of interest included patient age, timing of reconstruction (immediate versus delayed), disease stage, and pathologic findings of internal mammary lymph nodes. A total of 264 autologous breast reconstructions using the internal mammary vessels were performed in 204 patients with a median age of 44.5 years. The majority of reconstructions were immediate [n = 211 (79.9 percent)]. Seventy-two percent of patients had either stage I [72 patients (35.3 percent)] or stage II disease [75 patients (36.8 percent)]. Six patients were found to have internal mammary lymph node metastasis. Stage migration and alteration in adjuvant therapy occurred in all patients. Internal mammary lymph node sampling at the time of autologous breast reconstruction using the internal mammary system should become routine practice, as the morbidity associated with internal mammary lymph node harvest is low and the impact in cases of nodal involvement is quite substantial. Therapeutic, IV.

  5. The male mammary gland: a target for the xenoestrogen bisphenol A. (United States)

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


    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 (0.25-250μg/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. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Diet-induced obesity impairs mammary development and lactogenesis in murine mammary gland. (United States)

    Flint, David J; Travers, Maureen T; Barber, Michael C; Binart, Nadine; Kelly, Paul A


    We have developed a mouse model of diet-induced obesity that shows numerous abnormalities relating to mammary gland function. Animals ate approximately 40% more calories when offered a high-fat diet and gained weight at three times the rate of controls. They exhibited reduced conception rates, increased peripartum pup mortality, and impaired lactogenesis. The impairment of lactogenesis involved lipid accumulation in the secretory epithelial cells indicative of an absence of copius milk secretion. Expression of mRNAs for beta-casein, whey acid protein, and alpha-lactalbumin were all decreased immediately postpartum but recovered as lactation was established over 2-3 days. Expression of acetyl-CoA carboxylase (ACC)-alpha mRNA was also decreased at parturition as was the total enzyme activity, although there was a compensatory increase in the proportion in the active state. By day 10 of lactation, the proportion of ACC in the active state was also decreased in obese animals, indicative of suppression of de novo fatty acid synthesis resulting from the supply of preformed fatty acids in the diet. Although obese animals consumed more calories in the nonpregnant and early pregnant states, they showed a marked depression in fat intake around day 9 of pregnancy before food intake recovered in later pregnancy. Food intake increased dramatically in both lean and obese animals during lactation although total calories consumed were identical in both groups. Thus, despite access to high-energy diets, the obese animals mobilized even more adipose tissue during lactation than their lean counterparts. Obese animals also exhibited marked abnormalities in alveolar development of the mammary gland, which may partially explain the delay in differentiation evident during lactogenesis.

  7. Characterization of the Six1 homeobox gene in normal mammary gland morphogenesis

    Directory of Open Access Journals (Sweden)

    McManaman James L


    Full Text Available Abstract Background The Six1 homeobox gene is highly expressed in the embryonic mammary gland, continues to be expressed in early postnatal mammary development, but is lost when the mammary gland differentiates during pregnancy. However, Six1 is re-expressed in breast cancers, suggesting that its re-instatement in the adult mammary gland may contribute to breast tumorigenesis via initiating a developmental process out of context. Indeed, recent studies demonstrate that Six1 overexpression in the adult mouse mammary gland is sufficient for initiating invasive carcinomas, and that its overexpression in xenograft models of mammary cancer leads to metastasis. These data demonstrate that Six1 is causally involved in both breast tumorigenesis and metastasis, thus raising the possibility that it may be a viable therapeutic target. However, because Six1 is highly expressed in the developing mammary gland, and because it has been implicated in the expansion of mammary stem cells, targeting Six1 as an anti-cancer therapy may have unwanted side effects in the breast. Results We sought to determine the role of Six1 in mammary development using two independent mouse models. To study the effect of Six1 loss in early mammary development when Six1 is normally expressed, Six1-/- embryonic mammary glands were transplanted into Rag1-/- mice. In addition, to determine whether Six1 downregulation is required during later stages of development to allow for proper differentiation, we overexpressed Six1 during adulthood using an inducible, mammary-specific transgenic mouse model. Morphogenesis of the mammary gland occurred normally in animals transplanted with Six1-/- embryonic mammary glands, likely through the redundant functions of other Six family members such as Six2 and Six4, whose expression was increased in response to Six1 loss. Surprisingly, inappropriate expression of Six1 in the adult mammary gland, when levels are normally low to absent, did not inhibit

  8. Radix bupleuri Extract Inhibits Hyperplasia of Mammary Gland in Rats

    African Journals Online (AJOL)

    Purpose: To investigate the effect of Radix bupleuri extract (RBE) on hyperplasia of mammary gland (HMG) in rats. Methods: Forty virgin female Wistar rats were randomly divided into control, HMG model, positive control (Rupisanjie capsule, RPSJC), and low-, middle-, and high-dose RBE groups. Estrogen and ...

  9. Morphogenesis of Mammary Glands in Buffalo (Bubalus bubalis

    Directory of Open Access Journals (Sweden)

    Amit Challana


    Full Text Available The present research was elucidated on the morphogenesis of mammary gland of buffalo during prenatal development. Total of 16 foetuses ranging from 1.2 cm (34 days to 108 cm CVRL (curved crown rump length (317 days were used for study. The study revealed that mammary line was first observed at 1.2 cm CVRL (34 days, mammary hillock at 1.7 cm (37 days, and mammary bud at 2.6 cm CVRL (41 days foetuses. Epidermal cone was found at 6.7 cm CVRL (58 days whereas primary and secondary ducts were observed at 7.4 cm CVRL (62 days and 15 cm CVRL (96 days, respectively. Connective tissue whorls were reported at 18.2 cm CVRL (110 days and internal elastic lamina and muscle layers at 24.1 cm CVRL (129 days. Lobules were observed at 29.3 cm CVRL (140 days, rosette of furstenberg at 39.5 cm CVRL (163 days, and keratin plug at 45.5 cm CVRL (176 days foetus. Primordia of sweat and sebaceous glands around hair follicle were seen at 21.2 cm CVRL (122 days of foetal life. Differentiation of all the skin layers along with cornification was observed at 69 cm (229 days in group III foetuses.

  10. Mammary gland stem cells: More puzzles than explanations

    Indian Academy of Sciences (India)


    Apr 28, 2012 ... 3238–3243. Jiang S, Lee B-C, Fu Y, Avraham S, Lim B and Avraham HK 2010. Reconstitution of mammary epithelial morphogenesis by murine embryonic stem cells undergoing hematopoietic stem cell dif- ferentiation. PLoS One 5 e9707. Jones C, Mackay A, Grigoriadis A, Cossu A, Reis-Filho JS, Fulford.

  11. Aflatoxins ingestion and canine mammary tumors: There is an association? (United States)

    Frehse, M S; Martins, M I M; Ono, E Y S; Bracarense, A P F R L; Bissoqui, L Y; Teixeira, E M K; Santos, N J R; Freire, R L


    The aim of this study was to determine the presence of mycotoxins on dogs feed and to explore the potential association between mycotoxins exposure and the chance of mamary tumors in a case-control study. The study included 256 female dogs from a hospital population, 85 with mammary tumors (case group) and 171 without mammary tumors (control group). An epidemiological questionnaire was applied to both groups, and the data were analyzed by the EpiInfo statistical package. For the study, 168 samples of the feed offered to dogs were analyzed for the presence of aflatoxins, fumonisins and zearalenone by high-performance liquid chromatography. Mycotoxins were found in 79 samples (100%) in the case group and 87/89 (97.8%) in the control group. Mycotoxins were detected in all types of feed, regardless feed quality. Level of aflatoxin B1 (p = 0.0356, OR = 2.74, 95%, CI 1.13 to 6.60), aflatoxin G1 (AFG1) (p = 0.00007, OR = 4.60, 95%, CI = 2.16 to 9.79), and aflatoxin G2 (AFG2) (p = 0.0133, OR = 9.91, 95%, CI 1.21 to 81.15) were statistically higher in case of mammary cancer. In contrast, neutering was a protective factor for mammary cancer (p = 0.0004, OR = 0.32, 95%, CI = 0.17 to 0.60). Copyright © 2015 Elsevier Ltd. All rights reserved.


    Directory of Open Access Journals (Sweden)

    Maja Zečević


    Full Text Available The aim of this study was to estimate ovarian changes in 7,12 dimethylbenz (α anthracene (DMBA induced rat mammary carcinomas. The study was carried out on female virgin albino Wistar rats (n=35, age=35-37days, body mass 120-140g, divided into control (n=10 and experimental group (n=25. Anesthetised animals of experimental group were inoculated with 2 mg mixture (1 mg of DMBA and 1 mg of cholesterol-buffer into the fifth left mammary gland. The animals were sacrificed 90 days after implantation, and ovaries and mammary glands were investigated. Mammary gland carcinomas (in situ and/or invasive were pathohistologically verified in 19 experimental animals. Histological, histochemical, and immunohistochemical (cytokeratin AE1/AE3 and PCNA studies of ovaries were performed.Besides non-neoplastic changes, such as decrease in ovary’s volume, reduction in the rate of follicular development and numerous corpora lutea formation were found in the vicinity of preneoplastic changes: papillomatous epithelial hyperplasia and inclusion cysts, microglandular formations with dysplasia and seromucinous microcystic formation. Intensive diffuse PCNA expression was present in the epithelium of glandlike structures, follicular and inclusion cysts.These morphological changes confirmed that DMBA is a pluripotent carcinogen capable to induce a wide spectrum of preneoplastic lesions in the ovaries. The present dilemma is whether the changes described are the consequence of the direct effects of DMBA or of hormonal activity of the induced breast carcinomas, or both.

  13. Notch3 marks clonogenic mammary luminal progenitor cells in vivo. (United States)

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


    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.

  14. Mammary gland chondrosarcoma in a German Shepherd bitch: A ...

    African Journals Online (AJOL)

    Canine mammary tumours are the most common tumours in intact bitches and they constitute about 25% of the neoplasm in this species followed by skin tumours (Benjamin et al.,1999) and their incidence varies from 198 to 622.6 cases per 100,000 dogs per year (Vail and MacEwen,2000). According to Yager et al.(1993) ...

  15. Ultrastructural changes in porcine mammary tissue during lactogenesis. (United States)

    Kensinger, R S; Collier, R J; Bazer, F W


    Ultrastructural changes occurring in porcine mammary tissue were characterised between Day 90 of pregnancy and Day 4 of lactation. Porcine mammary tissue on Day 90 of pregnancy was composed of alveoli which contained negligible to moderate amounts of secretion. Epithelial cells of these alveoli were relatively undifferentiated. The appearance and distribution of cellular organelles suggested that mammary epithelial differentiation had been initiated by Day 105 of pregnancy in the pig. A further increase in intracellular lipid droplets and granular endoplasmic reticulum suggested that differentiation had progressed by Day 112. On the day of parturition, secretions within the alveolar lumina assumed the appearance of normal milk (as opposed to colostrum) and the epithelia displayed a distinct cellular polarity characteristic of lactating mammary tissue. By Day 4 of lactation, differentiation of epithelial cells appeared to be complete, with dilated cisternae of the granular endoplasmic reticulum and with numerous secretory vesicles. Elongated microvilli were present and numerous cells contained lipid droplets which were being extruded into the lumina. Data from this and previous studies indicate that lactogenesis in the pig occurs in two stages. Stage 1 occurs between Days 90 and 105 of pregnancy, and Stage 2 between Days 112 of pregnancy and early lactation when the predominant feature is active milk secretion. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:3429308

  16. Mammary analogue secretory carcinoma: A rare salivary gland tumour

    African Journals Online (AJOL)

    Salivary gland malignancy is rare, with a global annual incidence of. 3 per 100 000 people.[1,2] A rare salivary gland tumour, mammary analogue secretory carcinoma (MASC), has only recently been described.[3] The few reports and studies concerning MASC have been published in several pathology journals. We report ...

  17. Cat Mammary Tumors: Genetic Models for the Human Counterpart

    Directory of Open Access Journals (Sweden)

    Filomena Adega


    Full Text Available The records are not clear, but Man has been sheltering the cat inside his home for over 12,000 years. The close proximity of this companion animal, however, goes beyond sharing the same roof; it extends to the great similarity found at the cellular and molecular levels. Researchers have found a striking resemblance between subtypes of feline mammary tumors and their human counterparts that goes from the genes to the pathways involved in cancer initiation and progression. Spontaneous cat mammary pre-invasive intraepithelial lesions (hyperplasias and neoplasias and malignant lesions seem to share a wide repertoire of molecular features with their human counterparts. In the present review, we tried to compile all the genetics aspects published (i.e., chromosomal alterations, critical cancer genes and their expression regarding cat mammary tumors, which support the cat as a valuable alternative in vitro cell and animal model (i.e., cat mammary cell lines and the spontaneous tumors, respectively, but also to present a critical point of view of some of the issues that really need to be investigated in future research.

  18. Induction of mammary gland tumor in female Sprague- Dawley rats ...

    African Journals Online (AJOL)

    Evaluation of blood enzymes showed significantly higher (P < 0.005) serum alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in tumor-bearing than in normal rats. This LA7 cell-induced rat mammary gland tumor model may be useful for studies in breast cancer drug or nutraceutical research and development.

  19. Altered oxidative stress and carbohydrate metabolism in canine mammary tumors

    Directory of Open Access Journals (Sweden)

    K. Jayasri


    Full Text Available Aim: Mammary tumors are the most prevalent type of neoplasms in canines. Even though cancer induced metabolic alterations are well established, the clinical data describing the metabolic profiles of animal tumors is not available. Hence, our present investigation was carried out with the aim of studying changes in carbohydrate metabolism along with the level of oxidative stress in canine mammary tumors. Materials and Methods: Fresh mammary tumor tissues along with the adjacent healthy tissues were collected from the college surgical ward. The levels of thiobarbituric acid reactive substances (TBARS, glutathione, protein, hexose, hexokinase, glucose-6-phosphatase, fructose-1, 6-bisphosphatase, and glucose-6-phosphate dehydrogenase (G6PD were analyzed in all the tissues. The results were analyzed statistically. Results: More than two-fold increase in TBARS and three-fold increase in glutathione levels were observed in neoplastic tissues. Hexokinase activity and hexose concentration (175% was found to be increased, whereas glucose-6-phosphatase (33%, fructose-1, 6-bisphosphatase (42%, and G6PD (5 fold activities were reduced in tumor mass compared to control. Conclusion: Finally, it was revealed that lipid peroxidation was increased with differentially altered carbohydrate metabolism in canine mammary tumors.

  20. Epidermal growth factor in mammary glands and milk from rats

    DEFF Research Database (Denmark)

    Thulesen, J; Raaberg, Lasse; Nexø, Ebba


    Epidermal growth factor (EGF) is one of the major growth-promoting agents in milk. Using immunohistochemistry we localized EGF in the mammary glands of lactating rats to the luminal border of the secretory cells. Following proteolytic pretreatment of the histological sections, the EGF...

  1. Laminin Mediates Tissue-specific Gene Expression in Mammary Epithelia

    Energy Technology Data Exchange (ETDEWEB)

    Streuli, Charles H; Schmidhauser, Christian; Bailey, Nina; Yurchenco, Peter; Skubitz, Amy P. N.; Roskelley, Calvin; Bissell, Mina J


    Tissue-specific gene expression in mammary epithelium is dependent on the extracellular matrix as well as hormones. There is good evidence that the basement membrane provides signals for regulating beta-casein expression, and that integrins are involved in this process. Here, we demonstrate that in the presence of lactogenic hormones, laminin can direct expression of the beta-casein gene. Mouse mammary epithelial cells plated on gels of native laminin or laminin-entactin undergo functional differentiation. On tissue culture plastic, mammary cells respond to soluble basement membrane or purified laminin, but not other extracellular matrix components, by synthesizing beta-casein. In mammary cells transfected with chloramphenicol acetyl transferase reporter constructs, laminin activates transcription from the beta-casein promoter through a specific enhancer element. The inductive effect of laminin on casein expression was specifically blocked by the E3 fragment of the carboxy terminal region of the alpha 1 chain of laminin, by antisera raised against the E3 fragment, and by a peptide corresponding to a sequence within this region. Our results demonstrate that laminin can direct tissue-specific gene expression in epithelial cells through its globular domain.

  2. Development and characterization of MCF7 mammary carcinoma ...

    African Journals Online (AJOL)

    Purpose: To investigate the development of mammary tumours in female Sprague-dawley rats through a simple subcutaneous injection of human adenocarcinoma breast cells (MCF7) in combination with basement membrane matrix (BME). Methods: Nine Sprague-Dawley rats were divided into three groups. Group A ...

  3. Ultrastructure of the human mammary gland. II. Postpartum lactogenesis. (United States)

    Tobon, H; Salazar, H


    The history and fine structure of 7 human mammary glands were studied in the post partum. Widespread hypertrophy and hyperplasia of the mammary acini were observed accompanied by dilatation and engorgement of the lumen by milk. Loose strands of connective tissue surrounding the mammary lobules and ductules contained dilated, engorged vascular channels. The lactogenic epithelial cells displayed rich cytoplasm containing prominent layering stacks of rough endoplasmic reticulum closely related to the enlarged oval mitochondria, on occasion surrounding their entire circumference. Also noted were numerous ribosomes and polyribosomes. The markedly hypertrophied golgi apparatus revealed cisternae containing particulate electron dense material and vesicles with dense granules. The latter were frequently seen being discharged in the lumen devoid of limiting membrane. Abundant fat droplets were present in the basal and apical regions and "pinched off" into the lumen, apparently surrounded by a limiting membrane. The lactogenic cells were richly endowed with slender microvilli in their luminal pole and related to one another by cytoplasmic prolongations, desmosomes and tight junctions. The myoepithelium was stretched and thinned out toward the periphery of the acini between the lactogenic epithelium and the basement lamina. Abundant myofilaments were present in the myoepithelial cells. Pinocytotic vesicles were also present, although not very numerous, in both the lactogenic and the myoepithelial cells. In general the human mammary gland during lactopoiesis follows similar structural changes as those previously described in other mammals.

  4. Three-dimensional cultures of mouse mammary epithelial cells. (United States)

    Mroue, Rana; Bissell, Mina J


    The mammary gland is an ideal "model organism" for studying tissue specificity and gene expression in mammals: it is one of the few organs that develop after birth and it undergoes multiple cycles of growth, differentiation and regression during the animal's lifetime in preparation for the important function of lactation. The basic "functional differentiation" unit in the gland is the mammary acinus made up of a layer of polarized epithelial cells specialized for milk production surrounded by myoepithelial contractile cells, and the two-layered structure is surrounded by basement membrane. Much knowledge about the regulation of mammary gland development has been acquired from studying the physiology of the gland and of lactation in rodents. Culture studies, however, were hampered by the inability to maintain functional differentiation on conventional tissue culture plastic. We now know that the microenvironment, including the extracellular matrix and tissue architecture, plays a crucial role in directing functional differentiation of organs. Thus, in order for culture systems to be effective experimental models, they need to recapitulate the basic unit of differentiated function in the tissue or organ and to maintain its three-dimensional (3D) structure. Mouse mammary culture models evolved from basic monolayers of cells to an array of complex 3D systems that observe the importance of the microenvironment in dictating proper tissue function and structure. In this chapter, we focus on how 3D mouse mammary epithelial cultures have enabled investigators to gain a better understanding of the organization, development and function of the acinus, and to identify key molecular, structural, and mechanical cues important for maintaining mammary function and architecture. The accompanying chapter of Vidi et al. describes 3D models developed for human cells. Here, we describe how mouse primary epithelial cells and cell lines--essentially those we use in our laboratory

  5. Comparative expression pathway analysis of human and canine mammary tumors

    Directory of Open Access Journals (Sweden)

    Marconato Laura


    Full Text Available Abstract Background Spontaneous tumors in dog have been demonstrated to share many features with their human counterparts, including relevant molecular targets, histological appearance, genetics, biological behavior and response to conventional treatments. Mammary tumors in dog therefore provide an attractive alternative to more classical mouse models, such as transgenics or xenografts, where the tumour is artificially induced. To assess the extent to which dog tumors represent clinically significant human phenotypes, we performed the first genome-wide comparative analysis of transcriptional changes occurring in mammary tumors of the two species, with particular focus on the molecular pathways involved. Results We analyzed human and dog gene expression data derived from both tumor and normal mammary samples. By analyzing the expression levels of about ten thousand dog/human orthologous genes we observed a significant overlap of genes deregulated in the mammary tumor samples, as compared to their normal counterparts. Pathway analysis of gene expression data revealed a great degree of similarity in the perturbation of many cancer-related pathways, including the 'PI3K/AKT', 'KRAS', 'PTEN', 'WNT-beta catenin' and 'MAPK cascade'. Moreover, we show that the transcriptional relationships between different gene signatures observed in human breast cancer are largely maintained in the canine model, suggesting a close interspecies similarity in the network of cancer signalling circuitries. Conclusion Our data confirm and further strengthen the value of the canine mammary cancer model and open up new perspectives for the evaluation of novel cancer therapeutics and the development of prognostic and diagnostic biomarkers to be used in clinical studies.

  6. Internal mammary lymph node management – further direction

    Directory of Open Access Journals (Sweden)

    Vrana D


    Full Text Available D Vrana,1,2 J Gatek3,4 1Department of Oncology, 2Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, 3Department of Surgery, Atlas Hospital, 4Faculty of Humanities, Tomas Bata University in Zlín, Zlín, Czech Republic We read the article titled “Internal mammary sentinel lymph node biopsy: abandon or persist?” by Qiu et al with high interest. This was an excellent paper regarding the contemporary management of internal mammary lymph nodes (IMLN in early-stage breast cancer1 and we would like to take this opportunity to comment on this paper.There are several unresolved questions regarding early-stage breast management including axillary staging, clear resection margin, or IMLN.2–4 We have been focusing on the issues of IMLN for almost a decade and just recently published our data regarding IMLN management. We absolutely agree that one has to carefully balance the benefit and potential risks of biopsy or radiotherapy of IMLN.  Authors' reply Peng-Fei Qiu, Yong-Sheng WangBreast Cancer Center, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, People’s Republic of China  We appreciate the letter from Professors Vrana and Gatek regarding our article titled “Internal mammary sentinel lymph node biopsy: abandon or persist?”.1 We have been following their publications regarding internal mammary lymph nodes (IMLN management since the publication of their article titled “Prognostic influence of internal mammary node drainage in patients with early-stage breast cancer” in December 20162 and we share their interest on this topic.  View the original paper by Qiu and colleagues.

  7. Internal mammary artery flow in different racial groups of Pakistan. (United States)

    Dar, Mudassir Iqbal; Dar, Asim Hassan; Ahmed, Mansoor; Haseeb, Abdul; Bilal, Muhammad


    To find out any differences in free flow of internal mammary artery among different ethnic groups. This observational, cross-sectional study was conducted at the Civil Hospital, Karachi, from January 2013 to December 2015, and comprised patients who underwent coronary artery bypass grafting. The participants were divided into 5 groups, i.e. Sindhi, Muslim migrants from India, Punjabi, Pathan and Balochi patients. Free flow of internal mammary artery was measured immediately after harvesting within a syringe, and its flow was measured in 30 seconds. SPSS 18 was used for data analysis. Of the 158 patients, 44(27.8%) were Sindhi, 33(20.9%) Punjabi, 8(5%) Baloch, 21(13.3%) Pathan and 52(32.9%) were migrants. The overall mean age was 52±8 years and the mean flow was 11.6±9.6ml per 30 seconds. The flow was 9.3±6 ml, 10±8ml, 13±11ml, 17±14ml and 15±13 ml in 30 seconds among migrants, Sindhi, Punjabi, Pathan and Baloch patients, respectively, with significant higher flow in Pathan patients compared to Sindhi and migrant patients (pflow of less than 5ml/30 sec was mostly found in migrants or Sindhi subjects 30/40(75%), and flow more than 30ml/ 30 seconds was found mostly in Baloch or Pathan patients 4/8(50%). Low flow internal mammary artery, which was used on left anterior descending artery, showed significantly higher need of inotropic support as compared to high flow internal mammary artery (p=0.004), more low cardiac output syndrome (p=0.022) and more use of intra-aortic balloon pump (p=0.028). Internal mammary artery flow was higher in Pathan and Baloch patients and low in migrants and Sindhis.

  8. Lesions of anogenital mammary-like glands: an update. (United States)

    Kazakov, Dmitry V; Spagnolo, Dominic V; Kacerovska, Denisa; Michal, Michal


    Long considered to be ectopic breast tissue representing the caudal remnants of the milk ridges, anogenital mammary-like glands are nowadays thought to represent a normal constituent of the anogenital area. Lesions involving these glands, benign or malignant, epithelial or stromal manifest a striking similarity to their mammary counterparts. This review addresses the recent literature on lesions of anogenital mammary-like glands and our personal experience with various lesions related to these structures. Discussed are the normal anatomy and histology of these glands as well as the clinical presentation, histopathological and immunohistochemical features, molecular biological aspects, and differential diagnosis of various lesions involving anogenital mammary-like glands, including lactating adenoma, hidradenoma papilliferum, hidradenocarcinoma papilliferum, fibroadenomas, phyllodes tumor, pseudoangiomatous stromal hyperplasia, extramammary Paget disease, and other carcinomas. In addition, "nonspecific" epithelial or stromal changes some of which can be likened to similar changes occurring in a range of benign breast disease, including sclerosing adenosis, columnar cell lesions, ductal lesions and various metaplastic changes affecting epithelium and myoepithelium are discussed. Although lesions of anogenital mammary-like glands are often discussed in many dermatopathology textbooks in the context of cutaneous adnexal neoplasms we advocate that the best approach to the diagnosis of these lesions is to relate them to analogous well recognized lesions occurring in the breast, that is, through the eyes of a breast pathologist. This will enable their recognition, precise classification and should introduce greater uniformity in how they are reported in the literature so that more meaningful clinicopathological comparisons and correlations may be made.

  9. Epimorphin Functions as a Key Morphoregulator for Mammary Epithelial Cells

    Energy Technology Data Exchange (ETDEWEB)

    Hirai, H.; Lochter, A.; Galosy, S.; Koshida, S.; Niwa, S.; Bissell, M.J.


    Hepatocyte growth factor (HGF) and EGF have been reported to promote branching morphogenesis of mammary epithelial cells. We now show that it is epimorphin that is primarily responsible for this phenomenon. In vivo, epimorphin was detected in the stromal compartment but not in lumenal epithelial cells of the mammary gland; in culture, however, a subpopulation of mammary epithelial cells produced significant amounts of epimorphin. When epimorphin-expressing epithelial cell clones were cultured in collagen gels they displayed branching morphogenesis in the presence of HGF, EGF, keratinocyte growth factor, or fibroblast growth factor, a process that was inhibited by anti-epimorphin but not anti-HGF antibodies. The branch length, however, was roughly proportional to the ability of the factors to induce growth. Accordingly, epimorphin-negative epithelial cells simply grew in a cluster in response to the growth factors and failed to branch. When recombinant epimorphin was added to these collagen gels, epimorphin-negative cells underwent branching morphogenesis. The mode of action of epimorphin on morphogenesis of the gland, however, was dependent on how it was presented to the mammary cells. If epimorphin was overexpressed in epimorphin-negative epithelial cells under regulation of an inducible promoter or was allowed to coat the surface of each epithelial cell in a nonpolar fashion, the cells formed globular, alveoli-like structures with a large central lumen instead of branching ducts. This process was enhanced also by addition of HGF, EGF, or other growth factors and was inhibited by epimorphin antibodies. These results suggest that epimorphin is the primary morphogen in the mammary gland but that growth factors are necessary to achieve the appropriate cell numbers for the resulting morphogenesis to be visualized.

  10. Mammary gland-specific ablation of focal adhesion kinase reduces the incidence of p53-mediated mammary tumour formation.

    NARCIS (Netherlands)

    Miltenburg, van M.H.; Nimwegen, van M.J.; Tijdens, R.B.; Lalai, R.A.; Kuiper, R.; Klarenbeek, S.; Schouten, P.C.; Vries, de A.; Jonkers, J.M.M.; Water, van de B.


    BACKGROUND Elevated expression of focal adhesion kinase (FAK) occurs in numerous human cancers including colon-, cervix- and breast cancer. Although several studies have implicated FAK in mammary tumour formation induced by ectopic oncogene expression, evidence supporting a role for FAK in

  11. Assessment of mammary gland metabolism in the sow. II. Cellular metabolites in the mammary secretion and plasma during lactogenesis II. (United States)

    Atwood, C S; Toussaint, J K; Hartmann, P E


    The concentrations of lactose, glucose, glucose 6-phosphate, glucose 1-phosphate, UDPglucose, UDPgalactose, UDP, UMP, inorganic phosphate, ADP and AMP (metabolites involved in the lactose synthesis pathway), and cAMP, galactose and fructose were measured in the mammary secretion from sucked (n = 9) and unsucked (n = 4) mammary glands of nine sows during the first 5 d post partum. The concentrations of lactose, glucose, galactose and fructose were also measured in plasma during this time. The progressive increase in the concentration of lactose, and changes in the concentrations of cellular metabolites in the mammary secretion from sucked glands were consistent with an increase in the metabolic activity of those glands during lactogenesis II. In contrast, unsucked glands showed a progressive decrease in the concentration of lactose, while the concentrations of cellular metabolites in the milk generally remained unchanged. These results indicated that there was no increase in the metabolic activity of unsucked glands (no increase in lactose synthesis or utilization of glucose and ATP) and that the rate of lactose synthesis prior to milk removal was limited by the availability of glucose and/or UDPgalactose. Therefore, the removal of colostrum from the mammary gland was necessary for an increase in the rate of lactose synthesis (and probably de novo fatty acid synthesis) and implies that autocrine mechanisms are operating to control the rate of milk synthesis during lactogenesis in the sow. The low concentration of glucose in colostrum compared with that in plasma is discussed in view of the paracellular pathway.

  12. Technical note: Measurement of mammary plasma flow in sows by downstream dilution of mammary vein infused para-aminohippuric acid

    DEFF Research Database (Denmark)

    Larsen, Uffe Krogh; Storm, Adam Christian; Theil, Peter Kappel


    catheter was surgically implanted in the femoral artery, and another 2 were inserted in the right cranial mammary vein of 8 second- and third-parity sows on d 76 ± 2 SEM of gestation. On the 3rd and 17th days in milk, arterial and venous blood samples were drawn in hourly intervals from 0.5 h before until...

  13. Comparative analysis of peptidylarginine deiminase-2 expression in canine, feline and human mammary tumours. (United States)

    Cherrington, B D; Mohanan, S; Diep, A N; Fleiss, R; Sudilovsky, D; Anguish, L J; Coonrod, S A; Wakshlag, J J


    The peptidylarginine deiminase (PAD) enzyme family converts arginine residues in proteins to citrulline. In the canine mammary gland, PAD2 expression is first detected in epithelial cells in oestrus and becomes more widely expressed during dioestrus. PAD2 appears to modify nuclear histones, suggesting a role for the enzyme in chromatin remodelling and gene regulation. Recent evidence suggests that PAD2 plays a role in gene regulation in primary human breast epithelial cells. PAD2 may therefore be involved in gene regulation as it relates to mammary development, the oestrus cycle and potentially to neoplasia. The aim of the present study was to determine whether PAD2 expression was increased or decreased in mammary carcinoma compared with normal mammary tissue. A human mammary tissue microarray and archival surgical biopsy tissues from canine and feline mammary tumours were used to demonstrate differential expression of PAD2 in mammary carcinoma that appeared to be consistent across species. Normal human and canine mammary epithelium showed strong cytoplasmic and nuclear expression of PAD2, but there was reduced PAD2 expression in mammary carcinomas from both species. Feline mammary carcinomas had complete loss of nuclear PAD2 expression. Loss of nuclear PAD2 expression may therefore represent a marker of progression towards more aggressive neoplasia. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Downregulation of ATM Gene and Protein Expression in Canine Mammary Tumors. (United States)

    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


    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 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.

  15. Piezoelectric particle accelerator (United States)

    Kemp, Mark A.; Jongewaard, Erik N.; Haase, Andrew A.; Franzi, Matthew


    A particle accelerator is provided that includes a piezoelectric accelerator element, where the piezoelectric accelerator element includes a hollow cylindrical shape, and an input transducer, where the input transducer is disposed to provide an input signal to the piezoelectric accelerator element, where the input signal induces a mechanical excitation of the piezoelectric accelerator element, where the mechanical excitation is capable of generating a piezoelectric electric field proximal to an axis of the cylindrical shape, where the piezoelectric accelerator is configured to accelerate a charged particle longitudinally along the axis of the cylindrical shape according to the piezoelectric electric field.

  16. Pubertal high fat diet: effects on mammary cancer development (United States)


    Introduction Epidemiological studies linking dietary fat intake and obesity to breast cancer risk have produced inconsistent results. This may be due to the difficulty of dissociating fat intake from obesity, and/or the lack of defined periods of exposure in these studies. The pubertal mammary gland is highly sensitive to cancer-causing agents. We assessed how high fat diet (HFD) affects inflammation, proliferative, and developmental events in the pubertal gland, since dysregulation of these can promote mammary tumorigenesis. To test the effect of HFD initiated during puberty on tumorigenesis, we utilized BALB/c mice, for which HFD neither induces obesity nor metabolic syndrome, allowing dissociation of HFD effects from other conditions associated with HFD. Methods Pubertal BALB/c mice were fed a low fat diet (12% kcal fat) or a HFD (60% kcal fat), and subjected to carcinogen 7,12-dimethylbenz[a]anthracene (DMBA)-induced tumorigenesis. Results HFD elevated mammary gland expression of inflammatory and growth factor genes at 3 and 4 weeks of diet. Receptor activator of nuclear factor kappa-B ligand (RANKL), robustly induced at 4 weeks, has direct mitogenic activity in mammary epithelial cells and, as a potent inducer of NF-κB activity, may induce inflammatory genes. Three weeks of HFD induced a transient influx of eosinophils into the mammary gland, consistent with elevated inflammatory factors. At 10 weeks, prior to the appearance of palpable tumors, there were increased numbers of abnormal mammary epithelial lesions, enhanced cellular proliferation, increased growth factors, chemokines associated with immune-suppressive regulatory T cells, increased vascularization, and elevated M2 macrophages. HFD dramatically reduced tumor latency. Early developing tumors were more proliferative and were associated with increased levels of tumor-related growth factors, including increased plasma levels of HGF in tumor-bearing animals. Early HFD tumors also had increased

  17. Autocrine-paracrine regulation of the mammary gland. (United States)

    Weaver, S R; Hernandez, L L


    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

  18. Proposed classification of the feline "complex" mammary tumors as ductal and intraductal papillary mammary tumors. (United States)

    Zappulli, V; Caliari, D; Rasotto, R; Ferro, S; Castagnaro, M; Goldschmidt, M


    When compared with the canine species, feline mammary tumors (FMTs) are much less heterogeneous, with a predominance of simple malignant neoplasm. Benign FMTs are rare, and it is unclear if complex and mixed tumors exist in the feline. In this study, we selected for immunohistochemical analyses 12 FMTs that had unusual histologic features. A group of 8 (2 benign and 6 malignant) FMTs showed a biphasic epithelial/myoepithelial population and a very regular cord-like distribution in a "Chinese lettering" pattern, within ectatic ducts. A second group (2 benign and 2 malignant) had an intraductal epithelial papillary growth pattern with a basally located monolayer of myoepithelial cells and a supporting fibrovascular stroma. The myoepithelial component always produced a standard immunohistochemical signature. All malignancies were grade I, and the subjects were all alive at 1 year postdiagnosis. On the basis of their morphology, we propose that they be classified as feline ductal adenoma/carcinoma and feline intraductal papillary adenoma/carcinoma, respectively. They overlap with their canine counterparts and lack the typical myoepithelial differentiation patterns seen in canine complex neoplasms, and therefore, the term complex should be avoided in felines. This study will add new information on FMT classification and be useful for prognostic studies.

  19. Similarity of GATA-3 Expression between Rat and Human Mammary Glands. (United States)

    Kinoshita, Yuichi; Yoshizawa, Katsuhiko; Emoto, Yuko; Yuki, Michiko; Yuri, Takashi; Shikata, Nobuaki; Tsubura, Airo


    The GATA family members are zinc finger transcription factors involved in cell differentiation and proliferation. In particular, GATA-3 is necessary for mammary gland maturation and is a useful marker in the characterization of mammary carcinoma in humans. The expression of GATA-3 protein in normal mammary glands, fibroadenomas and carcinomas was immunohistochemically compared in female rats and humans. In normal mammary glands of rats and humans, scattered luminal cells in the acini and whole ductal epithelial cells were positive for GATA-3 in the nuclei. No positive cells were detected in rat or human fibroadenomas. In rat and human mammary carcinomas, the nuclei of proliferating luminal-derived cancer cells expressed GATA-3. Therefore, GATA-3 protein is a candidate marker for mammary carcinoma in rats as well as humans.

  20. Role of T-Box Gene in Mammary Gland Development and Neoplasia (United States)


    Mammary Gland Development and Neoplasia PRINCIPAL INVESTIGATION: Virginia Papaioannou, Ph.D. CONTRACTING ORGANIZATION: Columbia University New York...of T-box Gene in Mammary Gland Development and Neoplasia DAMD17-96-1-6090 6. AUTHOR(S) Virginia E. Papaioannou, Ph.D. 7. PERFORMING ORGANIZATION NAME...hypothesis is that Tbx2 and TMx3 are required in the signalling pathway of nomal mammary gland development, and could also be involved in neoplasia

  1. The Role of BRCA1 in Suppressing Epithelial Mesenchymal Transition in Mammary Gland and Tumor Development (United States)


    pathology and expression of CK5 and CK14 in these samples with mouse mammary tumors. We noticed that both the tumor cell morphology and expression pattern...AWARD NUMBER: W81XWH-13-1-0282 TITLE: The Role of BRCA1 in Suppressing Epithelial-Mesenchymal Transition in Mammary Gland and Tumor...2013 - 31-AUG-2016 4. TITLE AND SUBTITLE The Role of BRCA1 in Suppressing Epithelial-Mesenchymal Transition in Mammary Gland and Tumor Development 5a

  2. Transcriptomic response of goat mammary epithelial cells to Mycoplasma agalactiae challenge – a preliminary study

    DEFF Research Database (Denmark)

    Ogorevc, Jernej; Mihevc, Sonja Prpar; Hedegaard, Jakob


    Mycoplasma agalactiae (Ma) is one of the main aetiological agents of intramammary infections in small ruminants, causing contagious agalactia. To better understand the underlying disease patterns a primary goat mammary epithelial cell (pgMEC) culture was established from the mammary tissue......, steroid metabolism, fatty acid metabolism, apoptosis signalling, transcription regulation, and cell cycle regulation. Based on the results we suggest that mammary epithelial cells in vivo contribute to the immune system by the induced expression of cytokines and other chemotactic agents, activation...

  3. A tumoriform lesion of the vulva with features of mammary-type fibrocystic disease. (United States)

    Konstantinova, Anastasia M; Kacerovska, Denisa; Michal, Michal; Kazakov, Dmitry V


    : Fibrocystic disease is a common benign lesion of the breast. Variably sized cysts, apocrine metaplasia, fibrosis, calcification, chronic inflammation, and epithelial hyperplasia are the basic morphological changes seen in mammary fibrocystic disease. We report a rare tumoriform lesion of the vulva with features of fibrocystic disease, which seems to be the first description of this condition in the vulva. The pertinent literature is discussed. The reported lesion further demonstrates the analogy between tumors of anogenital mammary-like glands and mammary neoplasms.

  4. Stem/progenitor cells in non-lactating versus lactating equine mammary gland


    Spaas, Jan; Chiers, Koen; Bussche, Leen; Burvenich, Christian; Van de Walle, Gerlinde


    The mammary gland is a highly regenerative organ that can undergo multiple cycles of proliferation, lactation, and involution. Based on the facts that (i) mammary stem/progenitor cells (MaSC) are proposed to be the driving forces behind mammary growth and function and (ii) variation exists between mammalian species with regard to physiological and pathological functioning of this organ, we believe that studying MaSC from different mammals is of great comparative interest. Over the years, impo...

  5. Modeling and analysis of transport in the mammary glands (United States)

    Quezada, Ana; Vafai, Kambiz


    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.

  6. Mammary remodelling and metabolic activity in dairy goats

    DEFF Research Database (Denmark)

    Safayi, Sina

    of epithelial cell proliferation and apoptosis; 2) the secretory activity of these cells, which in turn is affected by their differentiation; and 3) the provision of nutrients and removal of metabolic waste products via the blood. The present thesis aimed to address the hypotheses that 1) differences between PP...... is affected by the balance between the rate of epithelial cell proliferation and apoptosis; 2) the secretory activity of these cells, which in turn is affected by their differentiation; and 3) the provision of nutrients and removal of metabolic waste products via the blood. The present thesis aimed to address......, acetate or glucose) and determining the impact on milk yield and mammary nutrient uptake. The necessarily more metabolically active. The explanation why milk yield in dairy goats is relatively unaffected by CL (in contrast to dairy cows) remains to be established. In conclusion, mammary development...

  7. Significance of rat mammary tumors for human risk assessment. (United States)

    Russo, Jose


    We have previously indicated that the ideal animal tumor model should mimic the human disease. This means that the investigator should be able to ascertain the influence of host factors on the initiation of tumorigenesis, mimic the susceptibility of tumor response based on age and reproductive history, and determine the response of the tumors induced to chemotherapy. The utilization of experimental models of mammary carcinogenesis in risk assessment requires that the influence of ovarian, pituitary, and placental hormones, among others, as well as overall reproductive events are taken into consideration, since they are important modifiers of the susceptibility of the organ to neoplastic development. Several species, such as rodents, dogs, cats, and monkeys, have been evaluated for these purposes; however, none of them fulfills all the criteria specified previously. Rodents, however, are the most widely used models; therefore, this work will concentrate on discussing the rat rodent model of mammary carcinogenesis. © 2014 by The Author(s).

  8. Invasive ductal carcinoma of the mammary gland in a mare. (United States)

    Hirayama, K; Honda, Y; Sako, T; Okamoto, M; Tsunoda, N; Tagami, M; Taniyama, H


    A 21-year-old thoroughbred mare had a 35 x 14 x 10 cm mass involving the mammary gland. Metastases were found in the kidneys, lungs, skeletal muscles, and regional lymph nodes. Histopathologic examination of the tumor revealed a ductal solid carcinoma with extensive intraductal and intralobular involvement and focal infiltration of the adjacent stroma. The intralobular neoplasms were divided into irregularly shaped islands and sheets of polygonal and spindle-shaped epithelial cells by thick or thin fibrous connective tissue bundles. The neoplastic cells had a small or moderate amount of cytoplasm that stained faintly with eosin and round or oval hyperchromatic nuclei. Immunohistochemically, the neoplastic cells were strongly positive for Lu-5, weakly positive for AE1/AE3, vimentin, and glial fibrillary acidic protein, and negative for cytokeratin 8, cytokeratin 14, alpha-smooth muscle actin, calponin, and S100. The neoplasm was diagnosed as an invasive ductal carcinoma of the mammary gland with multiple metastases.


    Carpenter, Nancy A; Crook, Erika K


    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.

  10. Nasopharyngeal carcinoma metastasis to the mammary gland: A case report. (United States)

    Li, Shuang; Yang, Jiyuan


    Nasopharyngeal carcinoma is the second most common type of malignancy in Southern China. Metastatic sites are usually multifocal and involve the bones, lungs and distant lymph nodes. To date, there have been no studies with regard to nasopharyngeal carcinoma metastasis to the mammary gland. In the current study, the case of a 56-year-old female with nasal obstruction, epitaxis and a bilateral neck mass is presented. Following a series of examinations, the patient was diagnosed with nasopharyngeal carcinoma (cT3N3M0). Subsequently, the patient received radical radiation therapy. After three months, a mass was identified in the left breast, together with enlargement of multiple lymph nodes in the left axilla. The patient underwent a mastectomy and pathological examination revealed that the breast mass and axillary lymph node tissues were derived from the nasopharynx. To the best of our knowledge, this is the first report of a nasopharyngeal carcinoma that metastasized to the mammary gland.

  11. Mammary gland tumor formation in transgenic mice overexpressing stromelysin-1

    Energy Technology Data Exchange (ETDEWEB)

    Sympson, Carolyn J; Bissell, Mina J; Werb, Zena


    An intact basement membrane (BM) is essential for the proper function, differentiation and morphology of many epithelial cells. The disruption or loss of this BM occurs during normal development as well as in the disease state. To examine the importance of BM during mammary gland development in vivo, we generated transgenic mice that inappropriately express autoactivating isoforms of the matrix metalloproteinase stromelysin-1. The mammary glands from these mice are both functionally and morphologically altered throughout development. We have now documented a dramatic incidence of breast tumors in several independent lines of these mice. These data suggest that overexpression of stromelysin-1 and disruption of the BM may be a key step in the multi-step process of breast cancer.

  12. Perinatal ethinyl oestradiol alters mammary gland development in male and female Wistar rats

    DEFF Research Database (Denmark)

    Mandrup, Karen; Hass, Ulla; Christiansen, Sofie


    Increased attention is being paid to human mammary gland development because of concerns for environmental influences on puberty onset and breast cancer development. Studies in rodents have showed a variety of changes in the mammary glands after perinatal exposure to endocrine disrupting chemicals......, Wistar rats were exposed to 0, 5, 15 or 50 μg/kg of ethinyl oestradiol per day during gestation and lactation. A wide range of morphological parameters were evaluated in whole mounts of mammary glands from male and female offspring PD21–22. This study showed that in both male and female pre...... exposures may alter mammary gland development, disrupt lactation and alter susceptibility to breast cancer....

  13. Mammary alveolar epithelial cells convert to brown adipocytes in post-lactating mice

    DEFF Research Database (Denmark)

    Giordano, Antonio; Perugini, Jessica; Kristensen, David Møbjerg


    During pregnancy and lactation, subcutaneous white adipocytes in the mouse mammary gland transdifferentiate reversibly to milk-secreting epithelial cells. In this study, we demonstrate by transmission electron microscopy that in the post-lactating mammary gland interscapular multilocular adipocytes...... found close to the mammary alveoli contain milk protein granules. Use of the Cre-loxP recombination system allowed showing that the involuting mammary gland of whey acidic protein-Cre/R26R mice, whose secretory alveolar cells express the lacZ gene during pregnancy, contains some X...

  14. Slugging their way to immortality: driving mammary epithelial cells into a stem cell-like state. (United States)

    Soady, Kelly; Smalley, Matthew J


    Delineating the molecular factors that define and maintain the mammary stem cell state is vital for understanding normal development and tumourigenesis. A recent study by Guo and colleagues identifies two master transcriptional regulators of mammary stem cells, Slug and Sox9, ectopic expression of which confers stem cell attributes on differentiated mammary epithelial cells. Slug and Sox9 expression was also shown to determine in vivo metastatic potential of human breast cancer cell lines. Understanding these factors in the context of normal lineage differentiation is an important step toward elucidating the mammary epithelial cell hierarchy and the origins of cancer stem cells.

  15. Combined Telomerase Inhibition and Immunotherapy in the Prevention and Treatment of Mammary Carcinomas

    National Research Council Canada - National Science Library

    Gong, Jianlin


    .... The mammary carcinomas occur in multiple stages. In addition, the progressive malignant transformation is closely correlated with telomerase activity using telomeric repeat amplification protocol (TRAP...

  16. Regulation of Cripto-1 Signaling and Biological Activity by Caveolin-1 in Mammary Epithelial Cells


    Bianco, Caterina; Strizzi, Luigi; Mancino, Mario; Watanabe, Kazuhide; Gonzales, Monica; Hamada, Shin; Raafat, Ahmed; Sahlah, Lawson; Chang, Cindy; Sotgia, Federica; Normanno, Nicola; Lisanti, Michael; Salomon, David S.


    Human and mouse Cripto-1 (CR-1/Cr-1) proteins play an important role in mammary gland development and tumorigenesis. In this study, we examined the relationship between Cripto-1 and caveolin-1 (Cav-1), a membrane protein that acts as a tumor suppressor in the mammary gland. Cripto-1 was found to interact with Cav-1 in COS7 cells and mammary epithelial cells. Using EpH4 mouse mammary epithelial cells expressing Cr-1 (EpH4 Cr-1) or Cr-1 and Cav-1 (EpH4 Cr-1/Cav-1), we demonstrate that Cav-1 exp...

  17. Pro-inflammatory cytokines: Useful markers for the diagnosis of canine mammary tumours? (United States)

    Andaluz, Ana; Yeste, Marc; Rodríguez-Gil, Joan E; Rigau, Teresa; García, Félix; Rivera del Álamo, Maria Montserrat


    The aim of the present study was to analyse the expression of 60 pro-inflammatory cytokines as possible markers of malignancy in canine mammary tumours using a human cytokine antibody array. The cytokines were grouped into two different categories: (1) cytokines in which expression indicated the presence of a mammary tumour and (2) cytokines in which expression differentiated between simple mammary adenoma, tubulopapillary carcinoma or complex carcinoma. These data suggest that specific pro-inflammatory cytokines could be useful as tools for the diagnosis of canine mammary tumours. Copyright © 2016 Elsevier Ltd. All rights reserved.

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


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


    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 offspri...

  19. Developmental Expression of Claudins in the Mammary Gland. (United States)

    Baumgartner, Heidi K; Rudolph, Michael C; Ramanathan, Palaniappian; Burns, Valerie; Webb, Patricia; Bitler, Benjamin G; Stein, Torsten; Kobayashi, Ken; Neville, Margaret C


    Claudins are a large family of membrane proteins whose classic function is to regulate the permeability of tight junctions in epithelia. They are tetraspanins, with four alpha-helices crossing the membrane, two extracellular loops, a short cytoplasmic N-terminus and a longer and more variable C-terminus. The extracellular ends of the helices are known to undergo side-to-side (cis) interactions that allow the formation of claudin polymers in the plane of the membrane. The extracellular loops also engage in head-to-head (trans) interactions thought to mediate the formation of tight junctions. However, claudins are also present in intracellular structures, thought to be vesicles, with less well-characterized functions. Here, we briefly review our current understanding of claudin structure and function followed by an examination of changes in claudin mRNA and protein expression and localization through mammary gland development. Claudins-1, 3, 4, 7, and 8 are the five most prominent members of the claudin family in the mouse mammary gland, with varied abundance and intracellular localization during the different stages of post-pubertal development. Claudin-1 is clearly localized to tight junctions in mammary ducts in non-pregnant non-lactating animals. Cytoplasmic puncta that stain for claudin-7 are present throughout development. During pregnancy claudin-3 is localized both to the tight junction and basolaterally while claudin-4 is found only in sparse puncta. In the lactating mouse both claudin-3 and claudin-8 are localized at the tight junction where they may be important in forming the paracellular barrier. At involution and under challenge by lipopolysaccharide claudins -1, -3, and -4 are significantly upregulated. Claudin-3 is still colocalized with tight junction molecules but is also distributed through the cytoplasm as is claudin-4. These largely descriptive data provide the essential framework for future mechanistic studies of the function and regulation of

  20. Targeting the Prometastatic Microenvironment of the Involuting Mammary Gland (United States)


    information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for daily checking of vaginal plugs, with noon of the day of the plug considered day 0.5. Embryonic stages were confirmed by determining the degree of...LacZ expression underlies a route for axillary cell migration and is an early marker of the mammary mesenchyme We utilized an Ltbp1Llz/+ reporter mouse

  1. Bovine mammary stem cells: cell biology meets production agriculture. (United States)

    Capuco, A V; Choudhary, R K; Daniels, K M; Li, R W; Evock-Clover, C M


    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 repair. Accordingly, we and others have attempted to characterize and alter the function of bovine MaSC. In this review, we provide an overview of current knowledge of MaSC gained from studies using mouse and human model systems and present research on bovine MaSC within that context. Recent data indicate that MaSC retain labeled DNA for extended periods because of their selective segregation of template DNA strands during mitosis. Relying on this long-term retention of bromodeoxyuridine-labeled DNA, we identified putative bovine MaSC. These label-retaining epithelial cells (LREC) are in low abundance within mammary epithelium (laser microdissection and subsequent microarray analysis will hopefully provide markers for MaSC and insights into their regulation. Preliminary analyses of gene expression in laser-microdissected LREC and non-LREC are consistent with the concept that LREC represent populations of stem cells and progenitor cells that differ with regard to their properties and location within the epithelial layer. We have attempted to modulate the MaSC number by infusing a solution of xanthosine through the teat canal and into the ductal network of the mammary glands of prepubertal heifers. This treatment increased the number of putative stem cells, as evidenced by an increase in the percentage of LREC and increased telomerase activity within the tissue. The exciting possibility that stem cell expansion can influence milk production is currently under investigation.

  2. Migrastatin analogues inhibit canine mammary cancer cell migration and invasion.

    Directory of Open Access Journals (Sweden)

    Kinga Majchrzak

    Full Text Available BACKGROUND: Cancer spread to other organs is the main cause of death of oncological patients. Migration of cancer cells from a primary tumour is the crucial step in the complex process of metastasis, therefore blocking this process is currently the main treatment strategy. Metastasis inhibitors derived from natural products, such as, migrastatin, are very promising anticancer agents. Thus, the aim of our study was to investigate the effect of six migrastatin analogues (MGSTA-1 to 6 on migration and invasion of canine mammary adenocarcinoma cell lines isolated from primary tumours and their metastases to the lungs. Canine mammary tumours constitute a valuable tool for studying multiple aspect of human cancer. RESULTS: OUR RESULTS SHOWED THAT TWO OF SIX FULLY SYNTHETIC ANALOGUES OF MIGRASTATIN: MGSTA-5 and MGSTA-6 were potent inhibitors of canine mammary cancer cells migration and invasion. These data were obtained using the wound healing test, as well as trans-well migration and invasion assays. Furthermore, the treatment of cancer cells with the most effective compound (MGSTA-6 disturbed binding between filamentous F-actin and fascin1. Confocal microscopy analyses revealed that treatment with MGSTA-6 increased the presence of unbound fascin1 and reduced co-localization of F-actin and fascin1 in canine cancer cells. Most likely, actin filaments were not cross-linked by fascin1 and did not generate the typical filopodial architecture of actin filaments in response to the activity of MGSTA-6. Thus, administration of MGSTA-6 results in decreased formation of filopodia protrusions and stress fibres in canine mammary cancer cells, causing inhibition of cancer migration and invasion. CONCLUSION: Two synthetic migrastatin analogues (MGSTA-5 and MGSTA-6 were shown to be promising compounds for inhibition of cancer metastasis. They may have beneficial therapeutic effects in cancer therapy in dogs, especially in combination with other anticancer drugs

  3. The mammary gland and the homeobox gene Otx1. (United States)

    Pagani, Ilaria S; Terrinoni, Alessandro; Marenghi, Laura; Zucchi, Ileana; Chiaravalli, Anna M; Serra, Valeria; Rovera, Francesca; Sirchia, Silvia; Dionigi, Gianlorenzo; Miozzo, Monica; Mozzo, Monica; Frattini, Annalisa; Ferrari, Alberta; Capella, Carlo; Pasquali, Francesco; Lo Curto, Francesco; Curto, Francesco L; Albertini, Alberto; Melino, Gerry; Porta, Giovanni


    The mammary gland, the unique organ that primarily form at puberty, is an ideal model to study the functions of homeobox (HB) genes in both development and tumorigenesis. HB genes comprise a large family of developmental regulators that have a critical role in cell growth and differentiation. In the normal mammary gland, homeobox genes are involved in ductal formation, epithelial branching, and lobulo-alveolar development by regulating epithelial proliferation and differentiation. The HB genes are controlled in a spatial and temporal manner in both stromal and epithelial cells. They are coordinately regulated by hormones and extracellular matrix, suggesting that many signaling pathways are involved in homeobox gene functions. When homeobox genes are misexpressed in animal models, different defects are displayed in mammary gland development. Aberrant expression of homeobox genes, overexpressed or downregulated, is found in primary carcinomas and in breast cancer. The Otx1 HB gene is a classic regulatory of nervous system development during embryogenesis. Postnatally Otx1 is transcribed in the anterior pituitary gland, where activates transcription of the pituitary hormones, and plays a role in hematopoiesis, enhancing pluripotent cells, and erythroid differentiation. Otx1 can still be detected in mature cells of the erythroid and megacaryocytic lineage. During cyclical development of mammary gland, the Otx1 gene is overexpressed in lactation, confirming a role of this transcription factor in cell differentiation. Recent studies report that Otx1 is overexpressed in breast cancer. Otx1 is expressed during embryogenesis, and it is expressed again during carcinogenesis, implying its possible function in differentiation of neoplastic cells. © 2010 Wiley Periodicals, Inc.

  4. Construction of mammary gland specific expression plasmid pIN ...

    African Journals Online (AJOL)

    The backbone plasmid pBC1 contained goat β-casein 5′ arm and β-casein 3′ arm, to target mammary gland-specific gene expression. First, the igf-1 gene was cloned from liver tissue harvested from a Saanen dairy goat and inserted downstream of the β-casein 5' arm. Then the neo gene was amplified from plasmid ...

  5. Comparative characteristics of mammary glands cancer in humans and animals

    Directory of Open Access Journals (Sweden)

    Vorobyova О.V.


    Full Text Available


    This review is devoted to a comparative analysis of receptor status, immunity, angiogenesis, metastatic mammal glands cancer expression profiling in humans and animals. Angiogenesis has been assessed by quantitative and immunohistochemical characteristics by means of evaluation of microvascular density (MVD using Claudin-5 (CLDN-5 as a marker of vascular endothelium in tumors of mammary glands in dogs.

  6. The Pathology of EMT in Mouse Mammary Tumorigenesis


    Cardiff, Robert Darrell


    Epithelial-mesenchymal-transition (EMT) tumorigenesis in the mouse was first described over 100?years ago using various terms such as carcinosarcoma and without any comprehension of the underlying mechanisms. Such tumors have been considered artifacts of transplantation and of tissue culture. Recently, EMT tumors have been recognized in mammary glands of genetically engineered mice. This review provides a historical perspective leading to the current status in the context of some of the key m...

  7. Migrastatin analogues inhibit canine mammary cancer cell migration and invasion. (United States)

    Majchrzak, Kinga; Lo Re, Daniele; Gajewska, Małgorzata; Bulkowska, Małgorzata; Homa, Agata; Pawłowski, Karol; Motyl, Tomasz; Murphy, Paul V; Król, Magdalena


    Cancer spread to other organs is the main cause of death of oncological patients. Migration of cancer cells from a primary tumour is the crucial step in the complex process of metastasis, therefore blocking this process is currently the main treatment strategy. Metastasis inhibitors derived from natural products, such as, migrastatin, are very promising anticancer agents. Thus, the aim of our study was to investigate the effect of six migrastatin analogues (MGSTA-1 to 6) on migration and invasion of canine mammary adenocarcinoma cell lines isolated from primary tumours and their metastases to the lungs. Canine mammary tumours constitute a valuable tool for studying multiple aspect of human cancer. OUR RESULTS SHOWED THAT TWO OF SIX FULLY SYNTHETIC ANALOGUES OF MIGRASTATIN: MGSTA-5 and MGSTA-6 were potent inhibitors of canine mammary cancer cells migration and invasion. These data were obtained using the wound healing test, as well as trans-well migration and invasion assays. Furthermore, the treatment of cancer cells with the most effective compound (MGSTA-6) disturbed binding between filamentous F-actin and fascin1. Confocal microscopy analyses revealed that treatment with MGSTA-6 increased the presence of unbound fascin1 and reduced co-localization of F-actin and fascin1 in canine cancer cells. Most likely, actin filaments were not cross-linked by fascin1 and did not generate the typical filopodial architecture of actin filaments in response to the activity of MGSTA-6. Thus, administration of MGSTA-6 results in decreased formation of filopodia protrusions and stress fibres in canine mammary cancer cells, causing inhibition of cancer migration and invasion. Two synthetic migrastatin analogues (MGSTA-5 and MGSTA-6) were shown to be promising compounds for inhibition of cancer metastasis. They may have beneficial therapeutic effects in cancer therapy in dogs, especially in combination with other anticancer drugs. However, further in vivo studies are required to

  8. Nasopharyngeal carcinoma metastasis to the mammary gland: A case report


    Li, Shuang; Yang, Jiyuan


    Nasopharyngeal carcinoma is the second most common type of malignancy in Southern China. Metastatic sites are usually multifocal and involve the bones, lungs and distant lymph nodes. To date, there have been no studies with regard to nasopharyngeal carcinoma metastasis to the mammary gland. In the current study, the case of a 56-year-old female with nasal obstruction, epitaxis and a bilateral neck mass is presented. Following a series of examinations, the patient was diagnosed with nasopharyn...

  9. Automatic segmentation of histological structures in mammary gland tissue sections

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez-Gonzalez, Rodrigo; Deschamps, Thomas; Idica, Adam K.; Malladi, Ravikanth; Ortiz de Solorzano, Carlos


    Real-time three-dimensional (3D) reconstruction of epithelial structures in human mammary gland tissue blocks mapped with selected markers would be an extremely helpful tool for breast cancer diagnosis and treatment planning. Besides its clear clinical application, this tool could also shed a great deal of light on the molecular basis of breast cancer initiation and progression. In this paper we present a framework for real-time segmentation of epithelial structures in two-dimensional (2D) images of sections of normal and neoplastic mammary gland tissue blocks. Complete 3D rendering of the tissue can then be done by surface rendering of the structures detected in consecutive sections of the blocks. Paraffin embedded or frozen tissue blocks are first sliced, and sections are stained with Hematoxylin and Eosin. The sections are then imaged using conventional bright field microscopy and their background is corrected using a phantom image. We then use the Fast-Marching algorithm to roughly extract the contours of the different morphological structures in the images. The result is then refined with the Level-Set method which converges to an accurate (sub-pixel) solution for the segmentation problem. Finally, our system stacks together the 2D results obtained in order to reconstruct a 3D representation of the entire tissue block under study. Our method is illustrated with results from the segmentation of human and mouse mammary gland tissue samples.

  10. Clinicopathologic evaluation of mammary Paget′s disease

    Directory of Open Access Journals (Sweden)

    Meibodi Naser


    Full Text Available Mammary and extramammary Paget′s diseases are rare neoplasms of epidermis and mucosal epithelium. Due to their nonspecific and variable clinical view, they have differential diagnosis with eczema, melanoma, Bowen′s disease, etc. To the best of our knowledge, no such study has been performed in Iran regarding the prevalence, clinical aspects, underlying disease and pathological characteristics of these two diseases. In this study, we have evaluated the clinical and histopathological aspects of this disorder. Materials and Methods: In this retrospective study, all Paget′s biopsied samples referred to the Pathology Department of Imam-Reza hospital, Mashhad, since 1984 till 2004 were evaluated. Collected data were analyzed by descriptive statistical methods. Results: Among 98925 specimens, there were 29 cases of Paget′s disease. All cases were married women suffering from mammary Paget. The mean age was 53 ± 11 years. Left and right breast involvement was observed in 17 and 12 cases, all unilateral. The most common clinical view was ulcerated (27% and then erythematosus exudative plaques. More than 50% of patients were symptomatic. Most common symptoms were itching, pain and burning. The exclusive underlying pathological diagnosis was ductal carcinoma (55%. Discussion: In most cases, the clinical view of mammary Paget′s disease was helpful. Unilateral ulcerated plaque was the most common clinical sign. Majority of the accompanying pathology was ductal carcinoma. We had no cases of extramammary Paget′s disease in our study.

  11. Mammary candidiasis: A medical condition without scientific evidence? (United States)

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


    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".

  12. 2014 CERN Accelerator Schools: Plasma Wake Acceleration

    CERN Multimedia


    A specialised school on Plasma Wake Acceleration will be held at CERN, Switzerland from 23-29 November, 2014.   This course will be of interest to staff and students in accelerator laboratories, university departments and companies working in or having an interest in the field of new acceleration techniques. Following introductory lectures on plasma and laser physics, the course will cover the different components of a plasma wake accelerator and plasma beam systems. An overview of the experimental studies, diagnostic tools and state of the art wake acceleration facilities, both present and planned, will complement the theoretical part. Topical seminars and a visit of CERN will complete the programme. Further information can be found at:

  13. Mammary gland specific knockdown of the physiological surge in Cx26 during lactation retains normal mammary gland development and function.

    Directory of Open Access Journals (Sweden)

    Michael K G Stewart

    Full Text Available Connexin26 (Cx26 is the major Cx protein expressed in the human mammary gland and is up-regulated during pregnancy while remaining elevated throughout lactation. It is currently unknown if patients with loss-of-function Cx26 mutations that result in hearing loss and skin diseases have a greater susceptibility to impaired breast development. To investigate if Cx26 plays a critical role in mammary gland development and differentiation, a novel Cx26 conditional knockout mouse model was generated by crossing Cx26fl/fl mice with mice expressing Cre under the β-Lactoglobulin promoter. Conditional knockdown of Cx26 from the mammary gland resulted in a dramatic reduction in detectable gap junction plaques confirmed by a significant ∼65-70% reduction in Cx26 mRNA and protein throughout parturition and lactation. Interestingly, this reduction was accompanied by a decrease in mammary gland Cx30 gap junction plaques at parturition, while no change was observed for Cx32 or Cx43. Whole mount, histological and immunofluorescent assessment of breast tissue revealed comparatively normal lobuloalveolar development following pregnancy in the conditionally knockdown mice compared to control mice. In addition, glands from genetically-modified mice were capable of producing milk proteins that were evident in the lumen of alveoli and ducts at similar levels as controls, suggesting normal gland function. Together, our results suggest that low levels of Cx26 expression throughout pregnancy and lactation, and not the physiological surge in Cx26, is sufficient for normal gland development and function.

  14. Kinetics of mammary clonogenic cells and rat mammary cancer induction by X-rays or fission neutrons

    Energy Technology Data Exchange (ETDEWEB)

    Kamiya, Kenji [Hiroshima Univ. (Japan). Research Inst. for Radiation Biology and Medicine; Higgins, P.D.; Tanner, M.A.; Gould, M.N.; Clifton, K.H.


    Following the hormonal treatment of rats with high prolactin levels and glucocorticoid deficiency (Prl+/Glc-) for 48 days (Day +48), total recoverable mammary DNA was increased by more than sevenfold, tritiated thymidine uptake by nearly fourfold, and total mammary clonogens by about fivefold. Irradiation with 4, 40, and 80 cGy X-rays on Day +48 increased total mammary carcinomas per rat-day-at-risk linearly with dose, and 40 and 80 cGy significantly decreased first carcinoma latency. A dose of 40 cGy X-rays before hormone treatment (Day -1) yielded tumor latencies and frequencies insignificantly different from unirradiated controls but significantly different from those when the dose was given on Day +48. Total carcinomas per rat-day-at-risk were fitted better by a function of dose to the power 0.4 than by a linear function after exposure to 1, 10. and 20 cGy fission neutrons, and 10 and 20 cGy significantly shortened the time to appearance of the first cancer. In contrast to results with X-rays, 10 cGy neutrons on Day -1 yielded tumor frequencies and latencies insignificantly different from 10 cGy neutrons on Day +48. The carcinogenic action of X-rays, but not of neutrons, was thus influenced by total clonogen numbers and/or proliferation rates. (author)

  15. Mammary gland morphology in Sprague-Dawley rats following treatment with an organochlorine mixture in utero and neonatal genistein

    National Research Council Canada - National Science Library

    Foster, Warren G; Younglai, Edward V; Boutross-Tadross, Odette; Hughes, Claude L; Wade, Michael G

    ... of thoracic mammary glands was observed in female offspring at 200 days of age. Therefore, the objective of this study was to analyze the effect of in utero exposure to a mixture of toxicants on mammary gland morphology...

  16. Human milk protein production in xenografts of genetically engineered bovine mammary epithelial stem cells. (United States)

    Martignani, Eugenio; Eirew, Peter; Accornero, Paolo; Eaves, Connie J; Baratta, Mario


    In the bovine species milk production is well known to correlate with mammary tissue mass. However, most advances in optimizing milk production relied on improvements of breeding and husbandry practices. A better understanding of the cells that generate bovine mammary tissue could facilitate important advances in milk production and have global economic impact. With this possibility in mind, we show that a mammary stem cell population can be functionally identified and isolated from the bovine mammary gland. We also demonstrate that this stem cell population may be a promising target for manipulating the composition of cow's milk using gene transfer. We show that the in vitro colony-forming cell assay for detecting normal primitive bipotent and lineage-restricted human mammary clonogenic progenitors are applicable to bovine mammary cells. Similarly, the ability of normal human mammary stem cells to regenerate functional bilayered structures in collagen gels placed under the kidney capsule of immunodeficient mice is shared by a subset of bovine mammary cells that lack aldehyde dehydrogenase activity. We also find that this activity is a distinguishing feature of luminal-restricted bovine progenitors. The regenerated structures recapitulate the organization of bovine mammary tissue, and milk could be readily detected in these structures when they were assessed by immunohistochemical analysis. Transplantation of the bovine cells transduced with a lentivirus encoding human β-CASEIN led to expression of the transgene and secretion of the product by their progeny regenerated in vivo. These findings point to a common developmental hierarchy shared by human and bovine mammary glands, providing strong evidence of common mechanisms regulating the maintenance and differentiation of mammary stem cells from both species. These results highlight the potential of novel engineering and transplant strategies for a variety of commercial applications including the production of

  17. Quantitative Assessment of Mammary Gland Density in Rodents Using Digital Image Analysis

    Directory of Open Access Journals (Sweden)

    Thompson Henry J


    Full Text Available Abstract Background Rodent models have been used extensively to study mammary gland development and for studies of toxicology and carcinogenesis. Mammary gland gross morphology can visualized via the excision of intact mammary gland chains following fixation and staining with carmine using a tissue preparation referred to as a whole mount. Methods are described for the automated collection of digital images from an entire mammary gland whole mount and for the interrogation of digital data using a "masking" technique available with Image-Pro® plus image analysis software (Mediacybernetics. Silver Spring, MD. Results Parallel to mammographic analysis in humans, measurements of rodent mammary gland density were derived from area-based or volume-based algorithms and included: total circumscribed mammary fat pad mass, mammary epithelial mass, and epithelium-free fat pad mass. These values permitted estimation of absolute mass of mammary epithelium as well as breast density. The biological plausibility of these measurements was evaluated in mammary whole mounts from rats and mice. During mammary gland development, absolute epithelial mass increased linearly without significant changes in mammographic density. Treatment of rodents with tamoxifen, 9-cis-retinoic acid, or ovariectomy, and occurrence of diet induced obesity decreased both absolute epithelial mass and mammographic density. The area and volumetric methods gave similar results. Conclusions Digital image analysis can be used for screening agents for potential impact on reproductive toxicity or carcinogenesis as well as for mechanistic studies, particularly for cumulative effects on mammary epithelial mass as well as translational studies of mechanisms that explain the relationship between epithelial mass and cancer risk.

  18. Folic Acid Supplementation Promotes Mammary Tumor Progression in a Rat Model (United States)

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


    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

  19. Development of novel murine mammary imaging windows to examine wound healing effects on leukocyte trafficking in mammary tumors with intravital imaging. (United States)

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


    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.

  20. High Energy Particle Accelerators

    CERN Multimedia

    Audio Productions, Inc, New York


    Film about the different particle accelerators in the US. Nuclear research in the US has developed into a broad and well-balanced program.Tour of accelerator installations, accelerator development work now in progress and a number of typical experiments with high energy particles. Brookhaven, Cosmotron. Univ. Calif. Berkeley, Bevatron. Anti-proton experiment. Negative k meson experiment. Bubble chambers. A section on an electron accelerator. Projection of new accelerators. Princeton/Penn. build proton synchrotron. Argonne National Lab. Brookhaven, PS construction. Cambridge Electron Accelerator; Harvard/MIT. SLAC studying a linear accelerator. Other research at Madison, Wisconsin, Fixed Field Alternate Gradient Focusing. (FFAG) Oakridge, Tenn., cyclotron. Two-beam machine. Comments : Interesting overview of high energy particle accelerators installations in the US in these early years. .

  1. Improved plasma accelerator (United States)

    Cheng, D. Y.


    Converging, coaxial accelerator electrode configuration operates in vacuum as plasma gun. Plasma forms by periodic injections of high pressure gas that is ionized by electrical discharges. Deflagration mode of discharge provides acceleration, and converging contours of plasma gun provide focusing.

  2. The CERN Accelerator School

    CERN Multimedia


    Introduction to accelerator physics The CERN Accelerator School: Introduction to Accelerator Physics, which should have taken place in Istanbul, Turkey, later this year has now been relocated to Budapest, Hungary.  Further details regarding the new hotel and dates will be made available as soon as possible on a new Indico site at the end of May.

  3. Accelerators and Dinosaurs

    CERN Multimedia

    Turner, Michael Stanley


    Using naturally occuring particles on which to research might have made accelerators become extinct. But in fact, results from astrophysics have made accelerator physics even more important. Not only are accelerators used in hospitals but they are also being used to understand nature's inner workings by searching for Higgs bosons, CP violation, neutrino mass and dark matter (2 pages)

  4. File list: InP.Brs.50.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Brs.50.AllAg.Mammary_stem_cells mm9 Input control Breast Mammary stem cells SRX...185841 ...

  5. File list: InP.Brs.05.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Brs.05.AllAg.Mammary_stem_cells mm9 Input control Breast Mammary stem cells SRX...185841 ...

  6. Comparison between stearoyl-CoA desaturase expression in milk somatic cells and in mammary tissue of lactating dairy cows

    NARCIS (Netherlands)

    Jacobs, A.A.A.; Dijkstra, J.; Hendriks, W.H.; Baal, van J.; Vuuren, van A.M.


    Stearoyl-CoA desaturase (SCD) is an important enzyme in the bovine mammary gland, where it inserts a cis-double bond at the ¿9 position in a wide range of fatty acids. Investigating SCD expression in the bovine mammary gland generally requires invasive biopsy to obtain mammary tissue. The aim of

  7. File list: NoD.Brs.20.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Brs.20.AllAg.Mammary_epithelial_cells mm9 No description Breast Mammary epithel...ial cells ...

  8. File list: InP.Brs.50.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Brs.50.AllAg.Mammary_epithelial_cells mm9 Input control Breast Mammary cells SRX424873,SRX403487,SRX396750,SRX031066,SRX031214 ...

  9. Expression of tissue factor in canine mammary tumours and correlation with grade, stage and markers of haemostasis and inflammation

    DEFF Research Database (Denmark)

    Andreasen, Eva Bartholin; Nielsen, Ole Lerberg; Tranholm, M.


    Tissue factor (TF) expression in human cancers has been associated with a procoagulant state and facilitation of metastasis. This study was conducted in order to evaluate if TF was expressed in canine mammary tumours. Forty epithelial mammary tumours from 28 dogs were included. TF expression...... in a lymph node metastasis classified as anaplastic mammary carcinoma from a dog with concomitant disseminated intravascular coagulation (DIC)....

  10. File list: InP.Brs.10.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Brs.10.AllAg.Mammary_stem_cells mm9 Input control Breast Mammary stem cells SRX...185841 ...

  11. File list: NoD.Brs.50.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Brs.50.AllAg.Mammary_stem_cells mm9 No description Breast Mammary stem cells ...

  12. File list: NoD.Brs.10.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Brs.10.AllAg.Mammary_stem_cells mm9 No description Breast Mammary stem cells ...

  13. File list: InP.Brs.20.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Brs.20.AllAg.Mammary_epithelial_cells mm9 Input control Breast Mammary cells SRX424873,SRX403487,SRX396750,SRX031066,SRX031214 ...

  14. File list: NoD.Brs.05.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Brs.05.AllAg.Mammary_stem_cells mm9 No description Breast Mammary stem cells ...

  15. File list: InP.Brs.10.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Brs.10.AllAg.Mammary_epithelial_cells mm9 Input control Breast Mammary cells SRX424873,SRX031066,SRX031214,SRX396750,SRX403487 ...

  16. File list: InP.Brs.05.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Brs.05.AllAg.Mammary_epithelial_cells mm9 Input control Breast Mammary cells SRX424873,SRX403487,SRX031066,SRX031214,SRX396750 ...

  17. First demonstration of decorin, an extracellular matrix molecule, in bovine mammary tissue (United States)

    In the mammary gland, the extracellular matrix (ECM) is secreted by and surrounds cells located in both mammary parenchyma (PAR) and stroma. Decorin is an ECM proteoglycan with cell growth regulatory effects mediated by its ability to interact with growth factors or up-regulation of cyclin-dependent...

  18. A novel role of microRNA146b in promoting mammary alveolar progenitor cell maintenance. (United States)

    Elsarraj, Hanan S; Hong, Yan; Valdez, Kelli; Carletti, Martha; Salah, Sally M; Raimo, Monica; Taverna, Daniela; Prochasson, Philippe; Bharadwaj, Uddalak; Tweardy, David J; Christenson, Lane K; Behbod, Fariba


    In this report, we have shown that miR146b promotes the maintenance of pregnancy-derived mammary luminal alveolar progenitors. MiR146b expression was significantly higher in the mammary glands of pregnant and lactating mice than in virgin mice. Furthermore, miR146b levels were significantly higher in mouse mammary glands exposed to the sex hormones, estrogen and progesterone, compared with those of untreated control animals. Pregnancy-derived primary mouse mammary epithelial cells in which miR146b was knocked down showed a significant reduction in the number of hollow acinar organoid structures formed on three-dimensional Matrigel and in β-casein expression. This demonstrates that miR146b promotes the maintenance of pregnancy-derived mammary luminal alveolar progenitors. It has been shown that mouse mammary luminal progenitors give rise to hollow organoid structures, whereas solid organoid structures are derived from stem cells. Among several miR146b targets, miR146b knockdown resulted in preferential STAT3β overexpression. In the primary mouse mammary epithelial cells, overexpression of STAT3β isoform caused mammary epithelial cell death and a significant reduction in β-casein mRNA expression. Therefore, we conclude that during pregnancy miR146b is involved in luminal alveolar progenitor cell maintenance, at least partially, by regulating STAT3β.

  19. Regulation of Mammary Gland Sensitivity to Thyroid Hormones during the Transition from Pregnancy to Lactation (United States)

    Thyroid hormones are galactopoietic and appear to assist in establishing 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 Holstei...

  20. Effects of putrescine, cadaverine, spermine, spermidine and beta-phenylethylamine on cultured bovine mammary epithelial cells

    DEFF Research Database (Denmark)

    Fusi, Eleonora; Baldi, Antonella; Cheli, Federica


    A bovine mammary epithelial cell line (BME-UV1) and three-dimensional collagen primary bovine organoids were used to evaluate the effects of cadaverine, putrescine, spermine, spermicline and beta-phenylethylamine on mammary epithelial cells. Each biogenic amine was diluted in several concentratio...

  1. Mammary stem cells: Novel markers and novel approaches to increase lactation efficiency (United States)

    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...

  2. SHARPIN regulates collagen architecture and ductal outgrowth in the developing mouse mammary gland. (United States)

    Peuhu, Emilia; Kaukonen, Riina; Lerche, Martina; Saari, Markku; Guzmán, Camilo; Rantakari, Pia; De Franceschi, Nicola; Wärri, Anni; Georgiadou, Maria; Jacquemet, Guillaume; Mattila, Elina; Virtakoivu, Reetta; Liu, Yuming; Attieh, Youmna; Silva, Kathleen A; Betz, Timo; Sundberg, John P; Salmi, Marko; Deugnier, Marie-Ange; Eliceiri, Kevin W; Ivaska, Johanna


    SHARPIN is a widely expressed multifunctional protein implicated in cancer, inflammation, linear ubiquitination and integrin activity inhibition; however, its contribution to epithelial homeostasis remains poorly understood. Here, we examined the role of SHARPIN in mammary gland development, a process strongly regulated by epithelial-stromal interactions. Mice lacking SHARPIN expression in all cells (Sharpin cpdm ), and mice with a stromal (S100a4-Cre) deletion of Sharpin, have reduced mammary ductal outgrowth during puberty. In contrast, Sharpin cpdm mammary epithelial cells transplanted in vivo into wild-type stroma, fully repopulate the mammary gland fat pad, undergo unperturbed ductal outgrowth and terminal differentiation. Thus, SHARPIN is required in mammary gland stroma during development. Accordingly, stroma adjacent to invading mammary ducts of Sharpin cpdm mice displayed reduced collagen arrangement and extracellular matrix (ECM) stiffness. Moreover, Sharpin cpdm mammary gland stromal fibroblasts demonstrated defects in collagen fibre assembly, collagen contraction and degradation in vitro Together, these data imply that SHARPIN regulates the normal invasive mammary gland branching morphogenesis in an epithelial cell extrinsic manner by controlling the organisation of the stromal ECM. © 2016 The Authors.

  3. Mammary gland leptin in relation to lactogenesis in the periparturient dairy goat

    DEFF Research Database (Denmark)

    Rasmussen, Alice Neess; Nielsen, Mette Olaf; Tauson, Anne-Helene


    The role of leptin in development of mammary gland secretory function was studied during the periparturient period in dairy goats. Changes in mammary leptin and leptin receptor (short cytoplasmic form) expression were evaluated by real-time RT-PCR and related to changes in milk and plasma leptin ...

  4. The Snf1-related kinase, Hunk, is essential for mammary tumor metastasis

    NARCIS (Netherlands)

    Wertheim, Gerald B. W.; Yang, Thomas W.; Pan, Tien-Chi; Ramne, Anna; Liu, Zhandong; Gardner, Heather P.; Dugan, Katherine D.; Kristel, Petra; Kreike, Bas; van de Vijver, Marc J.; Cardiff, Robert D.; Reynolds, Carol; Chodosh, Lewis A.


    We previously identified a SNF1/AMPK-related protein kinase, Hunk, from a mammary tumor arising in an MMTV-neu transgenic mouse. The function of this kinase is unknown. Using targeted deletion in mice, we now demonstrate that Hunk is required for the metastasis of c-myc-induced mammary tumors, but

  5. Cellular Mechanisms in Regulating Mammary Cell Turnover During Lactation and Dry Period in Dairy Cows

    DEFF Research Database (Denmark)

    Nørgaard, J V; Theil, P K; Sørensen, M T


    The mechanisms involved in regulating mammary cell turnover during the pregnancy-lactaion cycle in dairy cows are unclear. The objective of present experiment was to describe expression of genes encoding proteins known to be involved in pathways regulating mammary cell proliferation, apoptosis, d...

  6. Human mammary progenitor cell fate decisions are productsof interactions with combinatorial microenvironments

    DEFF Research Database (Denmark)

    LaBarge, Mark A.; Nelson, Celeste M.; Villadsen, René


    combinations of cell-extrinsic mammary gland proteins and ECM molecules that imposed specific cell fates on bipotent human mammary progenitor cells.Micropatterned cell culture surfaces were fabricated to distinguish between the instructive effects of cell-cell versus cell-ECM interactions, as well......, maintain the progenitor state, and guide progenitor differentiation towards myoepithelial and luminal lineages....

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

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


    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. The Accelerator Reliability Forum

    CERN Document Server

    Lüdeke, Andreas; Giachino, R


    A high reliability is a very important goal for most particle accelerators. The biennial Accelerator Reliability Workshop covers topics related to the design and operation of particle accelerators with a high reliability. In order to optimize the over-all reliability of an accelerator one needs to gather information on the reliability of many different subsystems. While a biennial workshop can serve as a platform for the exchange of such information, the authors aimed to provide a further channel to allow for a more timely communication: the Particle Accelerator Reliability Forum [1]. This contribution will describe the forum and advertise it’s usage in the community.

  9. Cabergoline inhibits prolactin secretion and accelerates involution in dairy cows after dry-off. (United States)

    Boutinaud, M; Isaka, N; Lollivier, V; Dessauge, F; Gandemer, E; Lamberton, P; De Prado Taranilla, A I; Deflandre, A; Sordillo, L M


    cows. Cabergoline treatment also tended to increase fat content and somatic cell count more rapidly following dry-off compared with the control group. These changes in mammary secretion composition following the abrupt cessation of lactation indicate that cabergoline treatment facilitated dry-off and effectively accelerated mammary gland involution. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  10. Relationships between piglet growth rate and mammary gland size of the sow

    DEFF Research Database (Denmark)

    Nielsen, O.L.; Pedersen, Asger Roer; Sørensen, Martin Tang


    An experiment was conducted to study whether piglet growth rate is related to mammary gland size. It involved three primiparous sows and four multiparous sows that were fed ad libitum during the lactation period. The piglets received no creep feed. The weight and teat order of the piglets were......, intermediate in the middle and lowest in the rear glands. Average daily gain of the piglets was of the same magnitude regardless of gland position in the primiparous sows. In the multiparous sows, the piglets suckling the front teats had the highest gain while those suckling the middle teats had intermediate...... gain and those suckling the rear teats had the lowest gain. Average daily gain of the piglets in the lactation period was positively correlated to the amount of mammary tissue (0.35), mammary DNA (0.41) and mammary RNA (0.31), while correlations to mammary RNA concentration (0.28) and RNA/DNA ratio (0...

  11. Mammary adenocarcinomas in three male cats exposed to medroxyprogesterone acetate (1990-2006). (United States)

    Jacobs, Terry M; Hoppe, Bruce R; Poehlmann, Cathy E; Ferracone, Jackie D; Sorenmo, Karin U


    In this case series, three unrelated male housemate cats were treated repeatedly with injections of medroxyprogesterone acetate (MPA) for intercat aggression and urinary house soiling. All three cats subsequently developed multiple recurrent mammary adenocarcinomas and underwent numerous surgical resections. This report describes the clinical, histopathological and immunohistochemical findings in these three cats and highlights the potential for mammary carcinomas to develop in male cats years after receiving MPA injections. Extended survival times and a long delay between the administration of the progestin injections and the onset of mammary neoplasia are noted. Estrogen and progesterone receptor staining was performed on some of the tumors and the complex role of hormones in the pathogenesis and the prognosis of feline mammary carcinoma is discussed. Clinicians using MPA should institute life-long surveillance of their feline patients for mammary tumors. Copyright 2009 ESFM and AAFP. Published by Elsevier Ltd. All rights reserved.

  12. Mammary alveolar epithelial cells convert to brown adipocytes in post-lactating mice. (United States)

    Giordano, Antonio; Perugini, Jessica; Kristensen, David M; Sartini, Loris; Frontini, Andrea; Kajimura, Shingo; Kristiansen, Karsten; Cinti, Saverio


    During pregnancy and lactation, subcutaneous white adipocytes in the mouse mammary gland transdifferentiate reversibly to milk-secreting epithelial cells. In this study, we demonstrate by transmission electron microscopy that in the post-lactating mammary gland interscapular multilocular adipocytes found close to the mammary alveoli contain milk protein granules. Use of the Cre-loxP recombination system allowed showing that the involuting mammary gland of whey acidic protein-Cre/R26R mice, whose secretory alveolar cells express the lacZ gene during pregnancy, contains some X-Gal-stained and uncoupling protein 1-positive interscapular multilocular adipocytes. These data suggest that during mammary gland involution some milk-secreting epithelial cells in the anterior subcutaneous depot may transdifferentiate to brown adipocytes, highlighting a hitherto unappreciated feature of mouse adipose organ plasticity. © 2017 Wiley Periodicals, Inc.

  13. Signalling pathways implicated in early mammary gland morphogenesis and breast cancer.

    Directory of Open Access Journals (Sweden)

    Beatrice Howard


    Full Text Available Specification of mammary epithelial cell fate occurs during embryogenesis as cells aggregate to form the mammary anlage. Within the embryonic mammary bud, a population of epithelial cells exists that will subsequently proliferate to form a ductal tree filling the stromal compartment, and which can produce milk upon terminal differentiation after birth. Subsequently, these structures can be remodelled and returned to a basal state after weaning before regenerating in future pregnancies. The plasticity of the mammary epithelial cell, and its responsiveness to hormone receptors, facilitates this amazing biological feat, but aberrant signalling may also result in unintended consequences in the form of frequent malignancies. Reflecting this intimate connection, a considerable number of signalling pathways have been implicated in both mammary gland morphogenesis and carcinogenesis.

  14. Relationship between histology, development and tumorigenesis of mammary gland in female rat (United States)

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


    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

  15. Industrial Application of Accelerators

    CERN Multimedia

    CERN. Geneva


    At CERN, we are very familiar with large, high energy particle accelerators. However, in the world outside CERN, there are more than 35000 accelerators which are used for applications ranging from treating cancer, through making better electronics to removing harmful micro-organisms from food and water. These are responsible for around $0.5T of commerce each year. Almost all are less than 20 MeV and most use accelerator types that are somewhat different from what is at CERN. These lectures will describe some of the most common applications, some of the newer applications in development and the accelerator technology used for them. It will also show examples of where technology developed for particle physics is now being studied for these applications. Rob Edgecock is a Professor of Accelerator Science, with a particular interest in the medical applications of accelerators. He works jointly for the STFC Rutherford Appleton Laboratory and the International Institute for Accelerator Applications at the Univer...

  16. Industrial Application of Accelerators

    CERN Multimedia

    CERN. Geneva


    At CERN, we are very familiar with large, high energy particle accelerators. However, in the world outside CERN, there are more than 35000 accelerators which are used for applications ranging from treating cancer, through making better electronics to removing harmful micro-organisms from food and water. These are responsible for around $0.5T of commerce each year. Almost all are less than 20 MeV and most use accelerator types that are somewhat different from what is at CERN. These lectures will describe some of the most common applications, some of the newer applications in development and the accelerator technology used for them. It will also show examples of where technology developed for particle physics is now being studied for these applications. Rob Edgecock is a Professor of Accelerator Science, with a particular interest in the medical applications of accelerators. He works jointly for the STFC Rutherford Appleton Laboratory and the International Institute for Accelerator Applications at the Uni...

  17. The proto-oncogene Myc is essential for mammary stem cell function. (United States)

    Moumen, Mejdi; Chiche, Aurélie; Deugnier, Marie-Ange; Petit, Valérie; Gandarillas, Alberto; Glukhova, Marina A; Faraldo, Marisa M


    The mammary epithelium comprises two major cell lineages: basal and luminal. Basal cells (BCs) isolated from the mammary epithelium and transplanted into the mouse mammary fat pad cleared from the endogenous epithelium regenerate the mammary gland, strongly suggesting that the basal epithelial compartment harbors a long-lived cell population with multipotent stem cell potential. The luminal cell layer is devoid of the regenerative potential, but it contains cells with clonogenic capacity, the luminal progenitors. Mammary BCs and luminal progenitors express high levels of the transcription factor Myc. Here, we show that deletion of Myc from mammary basal epithelial cells led to impaired stem cell self-renewal as evaluated by limiting dilution and serial transplantation assays. Luminal progenitor population was significantly diminished in mutant epithelium suggesting control by the BC layer. Colony formation assay performed with isolated BCs showed that clonogenic capacity was abolished by Myc deletion. Moreover, transplanted BCs depleted of Myc failed to produce epithelial outgrowths. Stimulation with ovarian hormones estrogen (E) and progesterone (P) partially rescued the repopulation capacity of Myc-depleted BCs; however, the Myc-deficient mammary epithelium developed in response to E/P treatment lacked stem and progenitor cells. This study provides the first evidence that in the mammary gland, Myc has an essential nonredundant function in the maintenance of the self-renewing multipotent stem cell population responsible for the regenerative capacity of the mammary epithelium and is required downstream from ovarian hormones, for the control of mammary stem and progenitor cell functions. Copyright © 2012 AlphaMed Press.

  18. Canine Mammary Carcinomas: A Comparative Analysis of Altered Gene Expression

    Directory of Open Access Journals (Sweden)

    Farruk M. Lutful Kabir


    Full Text Available Breast cancer represents the second most frequent neoplasm in humans and sexually intact female dogs after lung and skin cancers, respectively. Many similar features in human and dog cancers including, spontaneous development, clinical presentation, tumor heterogeneity, disease progression and response to conventional therapies have supported development of this comparative model as an alternative to mice. The highly conserved similarities between canine and human genomes are also key to this comparative analysis, especially when compared to the murine genome. Studies with canine mammary tumor (CMT models have shown a strong genetic correlation with their human counterparts, particularly in terms of altered expression profiles of cell cycle regulatory genes, tumor suppressor and oncogenes and also a large group of non-coding RNAs or microRNAs (miRNAs. Because CMTs are considered predictive intermediate models for human breast cancer, similarities in genetic alterations and cancer predisposition between humans and dogs have raised further interest. Many cancer-associated genetic defects critical to mammary tumor development and oncogenic determinants of metastasis have been reported and appear to be similar in both species. Comparative analysis of deregulated gene sets or cancer signaling pathways has shown that a significant proportion of orthologous genes are comparably up- or down-regulated in both human and dog breast tumors. Particularly, a group of cell cycle regulators called cyclin-dependent kinase inhibitors (CKIs acting as potent tumor suppressors are frequently defective in CMTs. Interestingly, comparative analysis of coding sequences has also shown that these genes are highly conserved in mammals in terms of their evolutionary divergence from a common ancestor. Moreover, co-deletion and/or homozygous loss of the INK4A/ARF/INK4B (CDKN2A/B locus, encoding three members of the CKI tumor suppressor gene families (p16/INK4A, p14ARF and p15

  19. Chemoprevention of Rat Mammary Carcinogenesis by Apiaceae Spices

    Directory of Open Access Journals (Sweden)

    Farrukh Aqil


    Full Text Available 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

  20. Detection of Mouse Mammary Tumour Virus in house mice

    DEFF Research Database (Denmark)

    Steffensen, Lise K; Leirs, Herwig; Heiberg, Ann-Charlotte

    The prevalence of human breast cancer (HBC) is affected by several parameters. For the past decades MMTV, Mouse Mammary Tumor Virus, known to cause breast cancer in mice, has been hypothesized to affect the frequency of hormone dependent HBC. Though conclusive evidence has not been produced, still...... and the fact that human cells can be infected in vitro strengthen the theory. Results from above mentioned studies indicate that the source of provirus is exogenous. The transmission mechanism is tentatively suggested to be by means of recombination of exogeneous and endogenous viruses obtained from...

  1. Mammary analogue secretory carcinoma: A rare salivary gland tumour

    Directory of Open Access Journals (Sweden)

    B S Jackson


    Full Text Available Mammary analogue secretory carcinoma (MASC is a rare and recently described tumour of the salivary glands. MASC has similar histomorphological and immunohistochemical features of secretory carcinoma of the breast. MASC can be mistaken for other salivary gland tumours, especially acinic cell carcinoma. A 28-year-old man was diagnosed with a rare salivary gland tumour in Pretoria, South Africa (SA. To our knowledge, a report of MASC in SA has not previously been published. The surgeons dealing with salivary gland tumours should be aware of the clinical presentation. Current treatment is similar to that of other salivary gland malignancies.

  2. The mammary myoepithelial cell - Cinderella or ugly sister? (United States)

    Lakhani, Sunil R; O'Hare, Michael J


    The breast myoepithelial cell is the Cinderella of mammary biology. Although its contribution to benign and some malignant pathologies is recognised, it has been largely neglected in molecular and biological studies. The reason for this has been the perception that its role in normal physiology is confined to lactation and the belief that most breast cancers arise from luminal epithelial cells. This review presents our perspective on its broader biological significance and its potential use as a model system for understanding breast carcinogenesis. PMID:11250738

  3. Mammary analogue secretory carcinoma: A rare salivary gland tumour. (United States)

    Jackson, B S; Pratt, T L; Van Rooyen, A


    Mammary analogue secretory carcinoma (MASC) is a rare and recently described tumour of the salivary glands. MASC has similar histomorphological and immunohistochemical features of secretory carcinoma of the breast. MASC can be mistaken for other salivary gland tumours, especially acinic cell carcinoma. A 28-year-old man was diagnosed with a rare salivary gland tumour in Pretoria, South Africa (SA). To our knowledge, a report of MASC in SA has not previously been published. The surgeons dealing with salivary gland tumours should be aware of the clinical presentation. Current treatment is similar to that of other salivary gland malignancies.

  4. [Mammary analog secretory carcinoma of the parotid gland]. (United States)

    Guérin, Maxime; Diedhiou, Abdoulaye; Nallet, Emmanuel; Duflo, Suzy; Laé, Marick; Wassef, Michel


    Mammary analog secretory carcinoma (MASC) of the parotid gland is a rare and recently described lesion. We report the case of a 46-year-old man with a tumor of the parotid gland which was carried to the diagnosis of MASC. Diagnostic was confirmed by highlighting the ETV6-NTRK3 gene translocation. However, some morphologic and immunohistochemical features are suggestive of this entity. This carcinoma should be distinguished from its main differential diagnoses: acinic cell carcinoma and low grade cribriform cystadenocarcinoma. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  5. Differential roles of ERα and ERβ in normal and neoplastic development in the mouse mammary gland. (United States)

    Mehta, Rajendra G; Hawthorne, Michael; Mehta, Rajeshwari R; Torres, Karen E O; Peng, Xinjian; McCormick, David L; Kopelovich, Levy


    The present experiments were performed to determine the roles of estrogen receptors α and β (ERα and ERβ) in normal and neoplastic development in the mouse mammary gland. In wild-type mice, in vivo administration of estradiol (E) + progesterone (P) stimulated mammary ductal growth and alveolar differentiation. Mammary glands from mice in which the ERβ gene has been deleted (βERKO mice) demonstrated normal ductal growth and differentiation in response to E + P. By contrast, mammary glands from mice in which the ERα gene has been deleted (αERKO mice) demonstrated only rudimentary ductal structures that did not differentiate in response to E + P. EGF demonstrates estrogen-like activity in the mammary glands of αERKO mice: treatment of αERKO mice with EGF + P (without E) supported normal mammary gland development, induced expression of progesterone receptor (PR), and increased levels of G-protein-coupled receptor (GPR30) protein. Mammary gland development in βERKO mice treated with EGF + P was comparable to that of wild-type mice receiving EGF + P; EGF had no statistically significant effects on the induction of PR or expression of GPR30 in mammary glands harvested from either wild-type mice or βERKO mice. In vitro exposure of mammary glands to 7,12-dimethylbenz[a]anthracene (DMBA) induced preneoplastic mammary alveolar lesions (MAL) in glands from wild-type mice and βERKO mice, but failed to induce MAL in mammary glands from αERKO mice. Microarray analysis of DMBA-treated mammary glands identified 28 functional pathways whose expression was significantly different in αERKO mice versus both βERKO and wild-type mice; key functions that were differentially expressed in αERKO mice included cell division, cell proliferation, and apoptosis. The data demonstrate distinct roles for ERα and ERβ in normal and neoplastic development in the mouse mammary gland, and suggest that EGF can mimic the ERα-mediated effects of E in this organ.

  6. Embryonic mammary signature subsets are activated in Brca1-/- and basal-like breast cancers (United States)


    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

  7. Accelerator and radiation physics

    CERN Document Server

    Basu, Samita; Nandy, Maitreyee


    "Accelerator and radiation physics" encompasses radiation shielding design and strategies for hadron therapy accelerators, neutron facilities and laser based accelerators. A fascinating article describes detailed transport theory and its application to radiation transport. Detailed information on planning and design of a very high energy proton accelerator can be obtained from the article on radiological safety of J-PARC. Besides safety for proton accelerators, the book provides information on radiological safety issues for electron synchrotron and prevention and preparedness for radiological emergencies. Different methods for neutron dosimetry including LET based monitoring, time of flight spectrometry, track detectors are documented alongwith newly measured experimental data on radiation interaction with dyes, polymers, bones and other materials. Design of deuteron accelerator, shielding in beam line hutches in synchrotron and 14 MeV neutron generator, various radiation detection methods, their characteriza...

  8. Nonparaxial accelerating Talbot effect

    CERN Document Server

    Zhang, Yiqi; Belić, Milivoj R; Li, Changbiao; Zhang, Zhaoyang; Wen, Feng; Zhang, Yanpeng; Xiao, Min


    We demonstrate the Talbot effect of nonpraxial accelerating beams, theoretically and numerically. It is based on the interference of nonparaxial accelerating solutions of the Helmholtz equation in two dimensions. The effect originates from the interference of such solutions that accelerate along concentric semicircular trajectories with different radii. The Talbot images form along certain central angles, which are referred to as the Talbot angles. These angles are inversely proportional to the radial differences between the nearest beams, which are equal and fixed. A single nonparaxial accelerating beam possesses duality - it can be viewed as a Talbot effect of itself with an infinite or zero Talbot angle. By choosing the coefficient for each beam component properly, we also obtain the fractional nonparaxial accelerating Talbot effect. These results improve the understanding of nonparaxial accelerating beams and the Talbot effect among them.

  9. Accelerator reliability workshop

    Energy Technology Data Exchange (ETDEWEB)

    Hardy, L.; Duru, Ph.; Koch, J.M.; Revol, J.L.; Van Vaerenbergh, P.; Volpe, A.M.; Clugnet, K.; Dely, A.; Goodhew, D


    About 80 experts attended this workshop, which brought together all accelerator communities: accelerator driven systems, X-ray sources, medical and industrial accelerators, spallation sources projects (American and European), nuclear physics, etc. With newly proposed accelerator applications such as nuclear waste transmutation, replacement of nuclear power plants and others. Reliability has now become a number one priority for accelerator designers. Every part of an accelerator facility from cryogenic systems to data storage via RF systems are concerned by reliability. This aspect is now taken into account in the design/budget phase, especially for projects whose goal is to reach no more than 10 interruptions per year. This document gathers the slides but not the proceedings of the workshop.

  10. Miniaturization Techniques for Accelerators

    Energy Technology Data Exchange (ETDEWEB)

    Spencer, James E.


    The possibility of laser driven accelerators [1] suggests the need for new structures based on micromachining and integrated circuit technology because of the comparable scales. Thus, we are exploring fully integrated structures including sources, optics (for both light and particle) and acceleration in a common format--an accelerator-on-chip (AOC). Tests suggest a number of preferred materials and techniques but no technical or fundamental roadblocks at scales of order 1 {micro}m or larger.

  11. Power Converters for Accelerators

    CERN Document Server

    Visintini, R.


    Particle accelerators use a great variety of power converters for energizing their sub-systems; while the total number of power converters usually depends on the size of the accelerator or combination of accelerators (including the experimental setup), the characteristics of power converters depend on their loads and on the particle physics requirements: this paper aims to provide an overview of the magnet power converters in use in several facilities worldwide.

  12. ER and PR signaling nodes during mammary gland development. (United States)

    Tanos, Tamara; Rojo, Lucia; Echeverria, Pablo; Brisken, Cathrin


    The ovarian hormones estrogen and progesterone orchestrate postnatal mammary gland development and are implicated in breast cancer. Most of our understanding of the molecular mechanisms of estrogen receptor (ER) and progesterone receptor (PR) signaling stems from in vitro studies with hormone receptor-positive cell lines. They have shown that ER and PR regulate gene transcription either by binding to DNA response elements directly or via other transcription factors and recruiting co-regulators. In addition they cross-talk with other signaling pathways through nongenomic mechanisms. Mouse genetics combined with tissue recombination techniques have provided insights about the action of these two hormones in vivo. It has emerged that hormones act on a subset of mammary epithelial cells and relegate biological functions to paracrine factors. With regards to hormonal signaling in breast carcinomas, global gene expression analyses have led to the identification of gene expression signatures that are characteristic of ERα-positive tumors that have stipulated functional studies of hitherto poorly understood transcription factors. Here, we highlight what has been learned about ER and PR signaling nodes in these different systems and attempt to lay out in which way the insights may converge.

  13. Control of mammary tumor differentiation by SKI-606 (bosutinib). (United States)

    Hebbard, L; Cecena, G; Golas, J; Sawada, J; Ellies, L G; Charbono, A; Williams, R; Jimenez, R E; Wankell, M; Arndt, K T; DeJoy, S Q; Rollins, R A; Diesl, V; Follettie, M; Chen, L; Rosfjord, E; Cardiff, R D; Komatsu, M; Boschelli, F; Oshima, R G


    C-Src is infrequently mutated in human cancers but it mediates oncogenic signals of many activated growth factor receptors and thus remains a key target for cancer therapy. However, the broad function of Src in many cell types and processes requires evaluation of Src-targeted therapeutics within a normal developmental and immune-competent environment. In an effort to understand the appropriate clinical use of Src inhibitors, we tested an Src inhibitor, SKI-606 (bosutinib), in the MMTV-PyVmT transgenic mouse model of breast cancer. Tumor formation in this model is dependent on the presence of Src, but the necessity of Src kinase activity for tumor formation has not been determined. Furthermore, Src inhibitors have not been examined in an autochthonous tumor model that permits assessment of effects on different stages of tumor progression. Here we show that oral administration of SKI-606 inhibited the phosphorylation of Src in mammary tumors and caused a rapid decrease in the Ezh2 Polycomb group histone H3K27 methyltransferase and an increase in epithelial organization. SKI-606 prevented the appearance of palpable tumors in over 50% of the animals and stopped tumor growth in older animals with pre-existing tumors. These antitumor effects were accompanied by decreased cellular proliferation, altered tumor blood vessel organization and dramatically increased differentiation to lactational and epidermal cell fates. SKI-606 controls the development of mammary tumors by inducing differentiation.

  14. Identity and dynamics of mammary stem cells during branching morphogenesis. (United States)

    Scheele, Colinda L G J; Hannezo, Edouard; Muraro, Mauro J; Zomer, Anoek; Langedijk, Nathalia S M; van Oudenaarden, Alexander; Simons, Benjamin D; van Rheenen, Jacco


    During puberty, the mouse mammary gland develops into a highly branched epithelial network. Owing to the absence of exclusive stem cell markers, the location, multiplicity, dynamics and fate of mammary stem cells (MaSCs), which drive branching morphogenesis, are unknown. Here we show that morphogenesis is driven by proliferative terminal end buds that terminate or bifurcate with near equal probability, in a stochastic and time-invariant manner, leading to a heterogeneous epithelial network. We show that the majority of terminal end bud cells function as highly proliferative, lineage-committed MaSCs that are heterogeneous in their expression profile and short-term contribution to ductal extension. Yet, through cell rearrangements during terminal end bud bifurcation, each MaSC is able to contribute actively to long-term growth. Our study shows that the behaviour of MaSCs is not directly linked to a single expression profile. Instead, morphogenesis relies upon lineage-restricted heterogeneous MaSC populations that function as single equipotent pools in the long term.

  15. Retrospective study and immunohistochemical analysis of canine mammary sarcomas. (United States)

    Dolka, Izabella; Sapierzyński, Rafał; Król, Magdalena


    Canine mammary sarcomas (CMSs) are rarely diagnosed in female dogs, which explains the scarcity of immunohistochemical findings concerning those tumors. This paper presents the results of a retrospective study into CMSs and discusses the clinical features of the analyzed tumors, the expression of intermediate filaments CK, Vim, Des and α-SMA, and the expression of p63, Ki67, ERα, PR and p53 protein. Four percent of all canine mammary tumors (CMTs) were classified as CMSs, and they represented 5.1% of malignant CMTs. The mean age at diagnosis was 11.1 ± 2.8 years. Large breed dogs were more frequently affected (38.7%). The majority of observed CMSs were fibrosarcomas (2.1%). All CMSs expressed vimentin, and higher levels of vimentin expression were noted in fibrosarcomas and osteosarcomas. Ki67 expression was significantly correlated with the grade of CMS. Our results revealed that CMSs form a heterogeneous group, therefore, immunohistochemical examinations could support differential and final diagnosis. Although this study analyzed a limited number of samples, the reported results can expand our knowledge about CMSs. Further work is required in this field.

  16. Neovascularization in canine mammary carcinoma – a case report

    Directory of Open Access Journals (Sweden)

    Alexandra Irimie


    Full Text Available The frequency of mammary tumors in canines is three times higher than in women. Contrast enhanced ultrasonography (CEUS is a noninvasive clinical method, that uses special contrast agents (CAs, their role being to layout the microvasculature of different lesions. The aim of this particular method, in this case, was to establish if we can evaluate the malignancy of a mass, given the fact that neovascularization is a malignancy marker. The case is represented by a Silky Terrier breed female dog, 5 years old, that was presented initially with an enlarged polycystic mammary gland and a nervous lactation. The female was initially diagnosed with polycystic mastosis. After 2 more months the mass became denser and enlarged. Before the ovariohisterectomy and unilateral mastectomy surgeries have taken place, a B-Mode standard ultrasound, CEUS and a pulmonary X-ray were performed. Our results integrate this case in “fast in” and “slow in” (type 2 curve. The histological diagnosis was established as a simple cystic papillary carcinoma with a malignancy grade 2. The mean value of the MVD was 13.75 which is a low MVD. We cannot determine a correlation between CEUS and a tumor’s malignancy, and so further studies are needed.


    Directory of Open Access Journals (Sweden)

    A. D. Zikiryakhodzhaev


    Full Text Available Phylloid (leaf-shaped breast tumors are a rare disease and constitute 0.3–0.5% of all breast tumors. Due to the rare frequency of occurrence, as well as the small number of randomized studies that have been conducted on this pathology, there is currently no standardized approach to the diagnosis and treatment of phylloid tumors. The reports about these rare cases appearing in the literature are, as a rule, descriptive, which only emphasizes the difficulty of differential diagnosis, the development of the correct tactics for treating such patients. In connection with the rarity, it is very difficult to diagnose correctly this pathology, which requires a highly qualified doctor as a diagnostician in the initial contact with such a patient, and a pathologist doctor who establishes the final morphological diagnosis. Often, leaf-shaped tumors are mistaken for mammary fibroadenomas. Such difficulties in correct diagnosis in the preoperative period can lead to errors in the planning of treatment. Also, the recommendations for the treatment of patients with this diagnosis are not fully understood, since up to now there are no accepted treatment standards in both Russian and foreign recommendations. Due to the fact that this pathology of mammary glands is rare, the principles of treatment are based on small retrospective studies and clinical observations. In this review, we will discuss the results of major retrospective studies, including data on epidemiology, etiology, diagnostic approach, strategies and results of treatment of this complex group of breast pathologies.

  18. Aberrant E-cadherin staining patterns in invasive mammary carcinoma

    Directory of Open Access Journals (Sweden)

    Brogi Edi


    Full Text Available Abstract Background E-cadherin, a cell surface protein involved in cell adhesion, is present in normal breast epithelium, benign breast lesions, and in breast carcinoma. Alterations in the gene CDH1 on chromosome 16q22 are associated with changes in E-cadherin protein expression and function. Inactivation of E-cadherin in lobular carcinomas and certain diffuse gastric carcinomas may play a role in the dispersed, discohesive "single cell" growth patterns seen in these tumors. The molecular "signature" of mammary lobular carcinomas is the loss of E-cadherin protein expression as evidenced by immunohistochemistry, whereas ductal carcinomas are typically E-cadherin positive. Patients and methods We report on E-cadherin immunostaining patterns in five cases of invasive mammary carcinoma Results These were five exceptional instances in which the E-cadherin immunophenotype did not correspond to the apparent histologic classification of the lesion. These cases which are exceedingly rare in our experience are the subject of this report. Conclusion Findings such as those illustrated in this study occur in virtually all biologic phenomena and they do not invalidate the very high degree of correlation between the expression of E-cadherin and the classification of breast carcinomas as ductal or lobular type on the basis of conventional histologic criteria.

  19. High Gradient Accelerator Research

    Energy Technology Data Exchange (ETDEWEB)

    Temkin, Richard [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Dept. of Physics. Plasma Science and Fusion Center


    The goal of the MIT program of research on high gradient acceleration is the development of advanced acceleration concepts that lead to a practical and affordable next generation linear collider at the TeV energy level. Other applications, which are more near-term, include accelerators for materials processing; medicine; defense; mining; security; and inspection. The specific goals of the MIT program are: • Pioneering theoretical research on advanced structures for high gradient acceleration, including photonic structures and metamaterial structures; evaluation of the wakefields in these advanced structures • Experimental research to demonstrate the properties of advanced structures both in low-power microwave cold test and high-power, high-gradient test at megawatt power levels • Experimental research on microwave breakdown at high gradient including studies of breakdown phenomena induced by RF electric fields and RF magnetic fields; development of new diagnostics of the breakdown process • Theoretical research on the physics and engineering features of RF vacuum breakdown • Maintaining and improving the Haimson / MIT 17 GHz accelerator, the highest frequency operational accelerator in the world, a unique facility for accelerator research • Providing the Haimson / MIT 17 GHz accelerator facility as a facility for outside users • Active participation in the US DOE program of High Gradient Collaboration, including joint work with SLAC and with Los Alamos National Laboratory; participation of MIT students in research at the national laboratories • Training the next generation of Ph. D. students in the field of accelerator physics.

  20. Accelerator Review Report 2014


    Tovey, Dan; Appleby, Rob; Bartolini, Riccardo; Bruning, Oliver; Clarke, Jim; Flint, Jonathan; Kilcoyne, Susan H.; Thomason, John; Jamieson, Charlotte; The Accelerator Science and Technology Centre (ASTeC); The Cockcroft Institute (CI); The John Adams Institute for Accelerator Science (JAI)


    The panel was created to review the accelerator programme and provide information on the breadth and scope of the STFC’s current accelerator R&D portfolio. The review’s prime driver is to underpin the development of the STFC accelerator landscape and strategy. The panel’s report will go to SB for comment and development of a high-level accelerator strategy, taking into account information from parallel reviews on neutron and photon activities. The ASB will then establish a more detailed accel...

  1. Mammary fat of breast cancer: gene expression profiling and functional characterization.

    Directory of Open Access Journals (Sweden)

    Fengliang Wang

    Full Text Available Mammary fat is the main composition of breast, and is the most probable candidate to affect tumor behavior because the fat produces hormones, growth factors and adipokines, a heterogeneous group of signaling molecules. Gene expression profiling and functional characterization of mammary fat in Chinese women has not been reported. Thus, we collected the mammary fat tissues adjacent to breast tumors from 60 subjects, among which 30 subjects had breast cancer and 30 had benign lesions. We isolated and cultured the stromal vascular cell fraction from mammary fat. The expression of genes related to adipose function (including adipogenesis and secretion was detected at both the tissue and the cellular level. We also studied mammary fat browning. The results indicated that fat tissue close to malignant and benign lesions exhibited distinctive gene expression profiles and functional characteristics. Although the mammary fat of breast tumors atrophied, it secreted tumor growth stimulatory factors. Browning of mammary fat was observed and browning activity of fat close to malignant breast tumors was greater than that close to benign lesions. Understanding the diversity between these two fat depots may possibly help us improve our understanding of breast cancer pathogenesis and find the key to unlock new anticancer therapies.

  2. Mammary gland development in transgenic male mice expressing human P450 aromatase. (United States)

    Li, Xiangdong; Wärri, Anni; Mäkelä, Sari; Ahonen, Tommi; Streng, Tomi; Santti, Risto; Poutanen, Matti


    We recently generated a transgenic mouse strain that expresses the human aromatase gene under the ubiquitin C promoter (AROM+). We have previously shown that in these mice the serum estradiol concentration is highly elevated, whereas the testosterone concentration is decreased. In the present study we examined mammary gland development in AROM+ male mice at different ages and found that the mammary glands of AROM+ males undergo ductal and alveolar development morphologically resembling that of terminally differentiated female mammary glands, expressing mRNA for a milk protein gene (beta-casein). The male mammary glands also express multiple hormone receptors typical for female mammary gland: estrogen receptor alpha and beta, progesterone receptor, and PRL receptor. Furthermore, data showed activation of the Stat5 (signal transducer and activator of transcription 5) signaling pathway in the AROM+ male mammary gland. Interestingly, the phenotype observed is in part reversible. Treatment with finrozole, a specific aromatase inhibitor, caused an involution of the differentiated phenotype of the mammary gland, marked by the disappearance of alveolar structures and the majority of the tertiary side branches of the ducts. The present animal model is a valuable tool for better understanding the cellular and molecular mechanisms involved in the development of gynecomastia.

  3. Lgr5-Expressing Cells Are Sufficient and Necessary for Postnatal Mammary Gland Organogenesis

    Directory of Open Access Journals (Sweden)

    Vicki Plaks


    Full Text Available Mammary epithelial stem cells are vital to tissue expansion and remodeling during various phases of postnatal mammary development. Basal mammary epithelial cells are enriched in Wnt-responsive cells and can reconstitute cleared mammary fat pads upon transplantation into mice. Lgr5 is a Wnt-regulated target gene and was identified as a major stem cell marker in the small intestine, colon, stomach, and hair follicle, as well as in kidney nephrons. Here, we demonstrate the outstanding regenerative potential of a rare population of Lgr5-expressing (Lgr5+ mammary epithelial cells (MECs. We found that Lgr5+ cells reside within the basal population, are superior to other basal cells in regenerating functional mammary glands (MGs, are exceptionally efficient in reconstituting MGs from single cells, and exhibit regenerative capacity in serial transplantations. Loss-of-function and depletion experiments of Lgr5+ cells from transplanted MECs or from pubertal MGs revealed that these cells are not only sufficient but also necessary for postnatal mammary organogenesis.

  4. Overexpression of Id1 in transgenic mice promotes mammary basal stem cell activity and breast tumorigenesis (United States)

    Won, Hee-Young; Jang, Ki-Seok; Min, Kyueng-Whan; Jang, Si-Hyong; Woo, Jong-Kyu; Oh, Seung Hyun; Kong, Gu


    Inhibitor of differentiation/DNA binding (Id)1 is a crucial regulator of mammary development and breast cancer progression. However, its effect on stemness and tumorigenesis in mammary epithelial cells remains undefined. Herein, we demonstrate that Id1 induces mammary tumorigenesis by increasing normal and malignant mammary stem cell (MaSC) activities in transgenic mice. MaSC-enriched basal cell expansion and increased self-renewal and in vivo regenerative capacity of MaSCs are observed in the mammary glands of MMTV-Id1 transgenic mice. Furthermore, MMTV-Id1 mice develop ductal hyperplasia and mammary tumors with highly expressed basal markers. Id1 also increases breast cancer stem cell (CSC) population and activity in human breast cancer lines. Moreover, the effects of Id1 on normal and malignant stem cell activities are mediated by the Wnt/c-Myc pathway. Collectively, these findings provide in vivo genetic evidence of Id1 functions as an oncogene in breast cancer and indicate that Id1 regulates mammary basal stem cells by activating the Wnt/c-Myc pathway, thereby contributing to breast tumor development. PMID:25938540

  5. Role of CXCR4 and SDF-1 in mammary tumor metastasis in the cat. (United States)

    Oonuma, Toshina; Morimatsu, Masami; Nakagawa, Takayuki; Uyama, Rina; Sasaki, Nobuo; Nakaichi, Munekazu; Tamamura, Hirokazu; Fujii, Nobutaka; Hashimoto, Shizu; Yamamura, Hozumi; Syuto, Bunei


    It has recently been suggested that the chemokine receptor CXCR4 and its ligand SDF-1 (CXCL12) promote metastasis of various cancers in humans. Since feline mammary tumors also metastasize to distant organs frequently, we used real-time quantitative PCR to examine the expression of feline CXCR4 (fCXCR4) in ten feline mammary tumor cell lines and seven feline mammary tumor tissues, and also the expression of feline SDF-1 (fSDF-1) in various organs. Cell lines derived from metastatic regions expressed more fCXCR4 than those derived from primary tumors. Mammary tumor tissues overexpressed more fCXCR4 than normal mammary tissues. Organs with high levels of fSDF-1 expression represent common sites of metastasis. Migration assays using the feline mammary tumor cell line NAC were also performed to test the activity of TN14003 and TC14012, antagonists of human CXCR4, to antagonize fCXCR4 expressed on NAC cells. TN14003 and TC14012 inhibited migration of NAC cells. We conclude that fCXCR4 may be a therapeutic target for feline mammary tumors.

  6. Redirection of Human Cancer Cells upon the Interaction with the Regenerating Mouse Mammary Gland Microenvironment

    Directory of Open Access Journals (Sweden)

    Sonia M. Rosenfield


    Full Text Available Tumorigenesis is often described as a result of accumulated mutations that lead to growth advantage and clonal expansion of mutated cells. There is evidence in the literature that cancer cells are influenced by the microenvironment. Our previous studies demonstrated that the mouse mammary gland is capable of redirecting mouse cells of non-mammary origins as well as Mouse Mammary Tumor Virus (MMTV-neu transformed cells toward normal mammary epithelial cell fate during gland regeneration. Interestingly, the malignant phenotype of MMTV-neu transformed cells was suppressed during serial transplantation experiments. Here, we discuss our studies that demonstrated the potential of the regenerating mouse mammary gland to redirect cancer cells of different species into a functional tumor-free mammary epithelial cell progeny. Immunochemistry for human specific CD133, mitochondria, cytokeratins as well as milk proteins and FISH for human specific probe identified human epithelial cell progeny in ducts, lobules, and secretory acini. Fluorescent In Situ Hybridization (FISH for human centromeric DNA and FACS analysis of propidium iodine staining excluded the possibility of mouse-human cell fusion. To our knowledge this is the first evidence that human cancer cells of embryonic or somatic origins respond to developmental signals generated by the mouse mammary gland microenvironment during gland regeneration in vivo.

  7. Mammary nutrient uptake in multiparous sows fed supplementary arginine during gestation and lactation

    DEFF Research Database (Denmark)

    Larsen, Uffe Krogh; Oksbjerg, Niels; Storm, Adam Christian


    from d 30 of gestation until weaning on d 28 of lactation and 2) to quantify mammary nutrient uptake in late gestation and in early and at peak lactation. Sows were surgically fitted with indwelling catheters on d 76 ± 2 SEM of gestation. Para-amino hippuric acid (pAH) was infused (3.0 mmol.......03) and net mammary flux (P = 0.01) of Ala were increased in CON sows, while the net flux of most other metabolites (P > 0.05) was unaffected by treatment. The mammary extraction of all essential AA was below 13% in late gestation. The average mammary extraction of essential AA at peak lactation was greatest......, we failed to observe an increased MPF and mammary uptake of AA and energy metabolites in ARG-supplemented sows. The mammary extraction rate of essential AA indicated that AA were not limiting for the mammary glands in late gestation, while Lys and Leu appeared to be the 2 most limiting essential AA...

  8. Premature mammary gland involution with repeated corticosterone injection in interleukin 10-deficient mice. (United States)

    Hwang, Woo-Sung; Bae, Ji-Hyun; Yeom, Su-Cheong


    Recently, we found that maternal stress could induce premature mammary gland involution in interleukin 10 knock out (IL-10 -/- ) mice. To elucidate correlation between stress, IL-10, and mammary gland involution, corticosterone was injected into the lactating wild type and IL-10-deficient mice and assessed mammary gland phenotype. Repetitive corticosterone injection developed premature mammary gland involution only in B6.IL-10 -/- mice; moreover, it induced alopecia in nursing pups. Corticosterone injection induced several typical changes such as mammary gland epithelial cell apoptosis, macrophage infiltration, fat deposition in adipocyte, STAT3 phosphorylation, and upregulation of tyrosine hydroxylase gene in adrenal gland. Overall incidence of pup alopecia and mammary gland involution was relatively high in corticosterone than control B6.IL-10 -/- group (57% vs. 20%). Our finding demonstrates that IL-10 is important for stress modulation, and B6.Il-10 -/- with corticosterone has several advantage such as simple to establish, well-defined onset of mammary gland involution, high incidence, and inducing pup alopecia.

  9. Conditionally reprogrammed normal and transformed mouse mammary epithelial cells display a progenitor-cell-like phenotype.

    Directory of Open Access Journals (Sweden)

    Francisco R Saenz

    Full Text Available Mammary epithelial (ME cells cultured under conventional conditions senesce after several passages. Here, we demonstrate that mouse ME cells isolated from normal mammary glands or from mouse mammary tumor virus (MMTV-Neu-induced mammary tumors, can be cultured indefinitely as conditionally reprogrammed cells (CRCs on irradiated fibroblasts in the presence of the Rho kinase inhibitor Y-27632. Cell surface progenitor-associated markers are rapidly induced in normal mouse ME-CRCs relative to ME cells. However, the expression of certain mammary progenitor subpopulations, such as CD49f+ ESA+ CD44+, drops significantly in later passages. Nevertheless, mouse ME-CRCs grown in a three-dimensional extracellular matrix gave rise to mammary acinar structures. ME-CRCs isolated from MMTV-Neu transgenic mouse mammary tumors express high levels of HER2/neu, as well as tumor-initiating cell markers, such as CD44+, CD49f+, and ESA+ (EpCam. These patterns of expression are sustained in later CRC passages. Early and late passage ME-CRCs from MMTV-Neu tumors that were implanted in the mammary fat pads of syngeneic or nude mice developed vascular tumors that metastasized within 6 weeks of transplantation. Importantly, the histopathology of these tumors was indistinguishable from that of the parental tumors that develop in the MMTV-Neu mice. Application of the CRC system to mouse mammary epithelial cells provides an attractive model system to study the genetics and phenotype of normal and transformed mouse epithelium in a defined culture environment and in vivo transplant studies.

  10. From genes to milk: genomic organization and epigenetic regulation of the mammary transcriptome. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Saasha Le


    Full Text Available 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.

  12. Stromal matrix metalloproteinase-11 is involved in the mammary gland postnatal development. (United States)

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


    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.

  13. ATM is required for SOD2 expression and homeostasis within the mammary gland. (United States)

    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


    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 AtmΔ/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 AtmΔ/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.

  14. Comparative pathology of mammary gland cancers in domestic and wild animals. (United States)

    Munson, Linda; Moresco, Anneke


    Mammary cancer occurs among all taxonomic groups, and comparing the disease in animals with breast cancer in women could greatly improve our understanding of the relevant risk factors and genetic profiles for this disease. Differences in cancer prevalence between carnivores and herbivores and between captive and wild carnivores are striking and support the hypotheses that diet and reproductive history are major risk factors. Domestic dogs and cats have a high prevalence of mammary tumors, and the majority of tumors in cats are aggressive cancers. Many domestic dogs and cats are prevented from breeding, resulting in their being exposed to recurrent estrogen peaks followed by high persistent levels of progesterone. Therefore progesterone appears to be a significant risk factor for cancer development. Supporting this suspicion is the observation that most mammary cancers in zoo cats are in those treated with the potent synthetic progestin contraceptive, melengestrol acetate. The more common morphologic types of mammary cancer in canids and felids include tubulopapillary, solid, cribriform, comedo and anaplastic carcinomas. Dogs also develop complex carcinomas, which likely evolve from the complex adenomas or mixed tumors that are so common in this species and are promoted by exogenous progesterone treatment. Among zoo felids, jaguars are at higher risk for mammary cancer and also have a high prevalence of ovarian papillarycystadenocarcinomas, a profile similar to women with BRCA1 mutations. As for women, estrogen (ER) and progesterone receptor (PR) expression varies in canine and feline mammary cancers. In general, ER expression is low, but PR expression persists in most cancers. Alterations in molecular controls of cell proliferation or survival in breast cancer, such as cyclin A and p53 expression, have been identified in dog and cat mammary cancers. Overall, spontaneous mammary cancers in cats and dogs make excellent models for human breast cancer, and knowledge of

  15. 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 (United States)

    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...

  16. ABC- and SLC-Transporters in Murine and Bovine Mammary Epithelium

    DEFF Research Database (Denmark)

    Yagdiran, Yagmur; Oskarsson, Agneta; Knight, Christopher H.


    , previously reported toinfluence BCRP in mammary cells, was investigated on transporter expression and functionin the two cell lines. Transporters studied were BCRP, MDR1, MRP1, OATP1A5/OATP1A2,OCTN1 and OCT1. Gene expressions of BCRP and OCT1 in murine mammary glandswere increased during gestation...... and lactation, whereas MDR1, MRP1, OATP1A5 and OCTN1 were decreased, compared to expressions in virgins. All transporters measured inmammary glands of mice were detected in bovine mammary tissue and in HC11 cells, while only MDR1 and MRP1 were detected in BME-UV cells. Prochloraz treatment induced MDR1 gene...

  17. Early detection, aggressive therapy: optimizing the management of feline mammary masses. (United States)

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


    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.


    Directory of Open Access Journals (Sweden)

    Paula de Lima Telmo


    Full Text Available Toxocariasis is a widespread zoonosis and is considered an important worldwide public health problem. The aim of this study was to investigate the frequency of trans-mammary Toxocara canis infection in newborn BALB/c mice nursed by females experimentally infected with 1,200 eggs after delivery. After 50 days of age, the presence of larvae in different organs of the offspring was investigated. Trans-mammary infection was confirmed in 73.9% of the mice that had been nursed by infected females. These data show a high trans-mammary transmission of T. canis and confirm the significance of this transmission route in paratenic hosts.

  19. Emerging evidence of the physiological role of hypoxia in mammary development and lactation (United States)


    Hypoxia is a physiological or pathological condition of a deficiency of oxygen supply in the body as a whole or within a tissue. During hypoxia, tissues undergo a series of physiological responses to defend themselves against a low oxygen supply, including increased angiogenesis, erythropoiesis, and glucose uptake. The effects of hypoxia are mainly mediated by hypoxia-inducible factor 1 (HIF-1), which is a heterodimeric transcription factor consisting of α and β subunits. HIF-1β is constantly expressed, whereas HIF-1α is degraded under normal oxygen conditions. Hypoxia stabilizes HIF-1α and the HIF complex, and HIF then translocates into the nucleus to initiate the expression of target genes. Hypoxia has been extensively studied for its role in promoting tumor progression, and emerging evidence also indicates that hypoxia may play important roles in physiological processes, including mammary development and lactation. The mammary gland exhibits an increasing metabolic rate from pregnancy to lactation to support mammary growth, lactogenesis, and lactation. This process requires increasing amounts of oxygen consumption and results in localized chronic hypoxia as confirmed by the binding of the hypoxia marker pimonidazole HCl in mouse mammary gland. We hypothesized that this hypoxic condition promotes mammary development and lactation, a hypothesis that is supported by the following several lines of evidence: i) Mice with an HIF-1α deletion selective for the mammary gland have impaired mammary differentiation and lipid secretion, resulting in lactation failure and striking changes in milk compositions; ii) We recently observed that hypoxia significantly induces HIF-1α-dependent glucose uptake and GLUT1 expression in mammary epithelial cells, which may be responsible for the dramatic increases in glucose uptake and GLUT1 expression in the mammary gland during the transition period from late pregnancy to early lactation; and iii) Hypoxia and HIF-1α increase the

  20. Continuous lactation in dairy cows: Effect on milk production and mammary nutrient supply and extraction

    DEFF Research Database (Denmark)

    Madsen, T. G.; Nielsen, M. O.; Andersen, Jens Bech


    Reports over the past decade have indicated that normal lactational performance can be achieved in genetically superior and high-producing dairy cows, even when the dry period between 2 lactations is omitted. The hypothesis tested in this experiment was that normal lactogenesis I and metabolic...... by the lactating mammary epithelial cells, nor to systemic endocrine changes. This suggests that lowered mammary nutrient uptake must have been associated with reduced mammary blood flow, metabolic activity, or both, most likely as a result of disturbed lactogenesis I prepartum or lactogenesis II postpartum...

  1. 78. Coronary bypass using bilateral internal mammary arteries in an achondroplast

    Directory of Open Access Journals (Sweden)

    Mohamed Abdulwahab Alassal


    Full Text Available Coronary bypass grafting for ischemic heart disease in achondroplastic dwarfs is very rare. Shortage of veins and sometimes, inadequate vein quality can cause difficulties during surgery. Only two achondroplastic cases were reported in literature that underwent coronary bypass surgery, in which the left internal mammary artery and vein grafts were used. To the best of our knowledge using bilateral internal mammary arteries in such patients was not reported. We report here a 55 years old male achondroplastic dwarf who had triple vessels coronary disease that underwent successful coronary bypass surgery using bilateral mammary arteries. Anatomic and surgical challenges in achondroplasia are highlighted

  2. Mifepristone inhibits MPA-and FGF2-induced mammary tumor growth but not FGF2-induced mammary hyperplasia

    Directory of Open Access Journals (Sweden)

    Juan P. Cerliani


    Full Text Available We have previously demonstrated a crosstalk between fibroblast growth factor 2 (FGF2 and progestins inducing experimental breast cancer growth. The aim of the present study was to compare the effects of FGF2 and of medroxyprogesterone acetate (MPA on the mouse mammary glands and to investigate whether the antiprogestin RU486 was able to reverse the MPA- or FGF2-induced effects on both, mammary gland and tumor growth. We demonstrate that FGF2 administered locally induced an intraductal hyperplasia that was not reverted by RU486, suggesting that FGF2-induced effects are progesterone receptor (PR-independent. However, MPA-induced paraductal hyperplasia was reverted by RU486 and a partial agonistic effect was observed in RU486-treated glands. Using C4-HD tumors which only grow in the presence of MPA, we showed that FGF2 administered intratumorally was able to stimulate tumor growth as MPA. The histology of FGF2-treated tumors showed different degrees of gland differentiation. RU486 inhibited both, MPA or FGF2 induced tumor growth. However, only complete regression was observed in MPA-treated tumors. Our results support the hypothesis that stromal FGF2 activates PR inducing hormone independent tumor growth.

  3. Beam Diagnostics for Accelerators

    CERN Document Server

    Koziol, Heribert


    This introductory course aims at a reasonably complete coverage of beam diagnostic devices used in linear and circular accelerators and in primary beam lines. The weight is on the concepts and the indication of variants, while for technical details the reader is referred to the literature. The present updated version replaces those from previous General Accelerator Physics Courses.

  4. Accelerators Beyond The Tevatron?

    Energy Technology Data Exchange (ETDEWEB)

    Lach, Joseph; /Fermilab


    Following the successful operation of the Fermilab superconducting accelerator three new higher energy accelerators were planned. They were the UNK in the Soviet Union, the LHC in Europe, and the SSC in the United States. All were expected to start producing physics about 1995. They did not. Why?

  5. Asia honours accelerator physicists

    CERN Multimedia


    "Steve Meyers of Cern and Jie Wei of Beijing's Tsinghua University are the first recipients of a new prize for particle physics. The pair were honoured for their contributions to numerous particle-accelerator projects - including Cern's Large Hadron Collider - by the Asian Committee for Future Accelerators (ACFA)..." (1 paragraph)

  6. KEK digital accelerator

    Directory of Open Access Journals (Sweden)

    T. Iwashita


    Full Text Available The High Energy Accelerator Research Organization KEK digital accelerator (KEK-DA is a renovation of the KEK 500 MeV booster proton synchrotron, which was shut down in 2006. The existing 40 MeV drift tube linac and rf cavities have been replaced by an electron cyclotron resonance (ECR ion source embedded in a 200 kV high-voltage terminal and induction acceleration cells, respectively. A DA is, in principle, capable of accelerating any species of ion in all possible charge states. The KEK-DA is characterized by specific accelerator components such as a permanent magnet X-band ECR ion source, a low-energy transport line, an electrostatic injection kicker, an extraction septum magnet operated in air, combined-function main magnets, and an induction acceleration system. The induction acceleration method, integrating modern pulse power technology and state-of-art digital control, is crucial for the rapid-cycle KEK-DA. The key issues of beam dynamics associated with low-energy injection of heavy ions are beam loss caused by electron capture and stripping as results of the interaction with residual gas molecules and the closed orbit distortion resulting from relatively high remanent fields in the bending magnets. Attractive applications of this accelerator in materials and biological sciences are discussed.

  7. The Atomki accelerator center (United States)

    Vajda, I.; Fülöp, Zs.; Biri, S.


    Particle accelerators are the driving forces of nuclear physics laboratories and MTA Atomki, the Institute for Nuclear Research of the Hungarian Academy of Sciences is no exception. The Atomki Accelerator Center (AAC) incorporates several low-energy charged-particle accelerators, offering the possibility of choosing ions with various charge states, energies and beam intensities. Currently, the AAC has six main facilities: a cyclotron (K=20), two Van de Graaff accelerators (1 MV, 5 MV), an ECR ion source, an electromagnetic isotope separator and a 2 MV Tandetron installed in 2015. The accelerators, spanning a range of beam energies from 50 eV to 27 MeV, have been designed for a broad range of research projects and applications in various fields - mainly in nuclear and atomic physics, materials science, environmental research and archaeology. The structure of the laboratory with a short description of the most important topics, education and outreach activities are presented.

  8. Bindings of the lectins Griffonia simplicifolia-1 and pokeweed mitogen mark discrete stages of myoepithelial-like differentiation of cell lines from the rat mammary gland. (United States)

    Rudland, P S; Hughes, C M


    Individual single-cell-cloned cell lines of the different rat mammary (Rama) cell types have been tested for their ability to bind the lectins Griffonia simplicifolia-1 (GS-1) and pokeweed mitogen (PWM) using fluorescent, histochemical, and radioactive assays. Myoepithelial-like cell lines isolated from neonatal rat mammary glands and from nonmetastasizing tumors strongly bind GS-1 and PWM, whereas the corresponding epithelial and fibroblastic cell lines do not. When the epithelial cell lines are grown on floating gels of polymerised rat tail collagen, the basally situated or peripheral cells are stained strongly with peroxidase-conjugated lectins, whereas the apically or luminally situated cells are unstained. The capacity of cell lines intermediate in morphology between epithelial and myoepithelial-like cells to bind to GS-1 is as follows: Rama 25 epithelial less than Rama 25-12 less than Rama 25-11 less than Rama 25-14 less than Rama 29 myoepithelial-like cells, the same order as for other markers of myoepithelial cells. Conjugated PWM, however, binds only to the myoepithelial-like cell lines. Treatment of Rama 25 epithelial cells with agents that disrupt microtubules accelerates their conversion to elongated, myoepithelial-like cells in culture. The binding of cells to GS-1 is observed prior to, and that to PWM after, the major morphological change. It is suggested that the stepwise appearances of carbohydrate receptors for GS-1 and PWM mark discrete stages in the differentiation of epithelial to myoepithelial-like cells in culture, in the same way that they mark similar differentiation stages in ductal development in mammary glands of prepubertal rats.

  9. The miniature accelerator

    CERN Multimedia

    Antonella Del Rosso


    The image that most people have of CERN is of its enormous accelerators and their capacity to accelerate particles to extremely high energies. But thanks to some cutting-edge studies on beam dynamics and radiofrequency technology, along with innovative construction techniques, teams at CERN have now created the first module of a brand-new accelerator, which will be just 2 metres long. The potential uses of this miniature accelerator will include deployment in hospitals for the production of medical isotopes and the treatment of cancer. It’s a real David-and-Goliath story.   Serge Mathot, in charge of the construction of the "mini-RFQ", pictured with the first of the four modules that will make up the miniature accelerator. The miniature accelerator consists of a radiofrequency quadrupole (RFQ), a component found at the start of all proton accelerator chains around the world, from the smallest to the largest. The LHC is designed to produce very high-intensity beams ...

  10. Multicavity proton cyclotron accelerator

    Directory of Open Access Journals (Sweden)

    J. L. Hirshfield


    Full Text Available A mechanism for acceleration of protons is described, in which energy gain occurs near cyclotron resonance as protons drift through a sequence of rotating-mode TE_{111} cylindrical cavities in a strong nearly uniform axial magnetic field. Cavity resonance frequencies decrease in sequence from one another with a fixed frequency interval Δf between cavities, so that synchronism can be maintained between the rf fields and proton bunches injected at intervals of 1/Δf. An example is presented in which a 122 mA, 1 MeV proton beam is accelerated to 961 MeV using a cascade of eight cavities in an 8.1 T magnetic field, with the first cavity resonant at 120 MHz and with Δf=8 MHz. Average acceleration gradient exceeds 40 MV/m, average effective shunt impedance is 223 MΩ/m, but maximum surface field in the cavities does not exceed 7.2 MV/m. These features occur because protons make many orbital turns in each cavity and thus experience acceleration from each cavity field many times. Longitudinal and transverse stability appear to be intrinsic properties of the acceleration mechanism, and an example to illustrate this is presented. This acceleration concept could be developed into a proton accelerator for a high-power neutron spallation source, such as that required for transmutation of nuclear waste or driving a subcritical fission burner, provided a number of significant practical issues can be addressed.

  11. Prevention and Treatment of Spontaneous Mammary Carcinoma with Dendritic Tumor Fusion Cell Vaccine

    National Research Council Canada - National Science Library

    Gong, Jianlin


    In the present study, the prevention of cancer development by vaccination with fusion cells was evaluated In a genetically engineered murine model which develops spontaneous mammary carcinomas. The mice (MMT...

  12. Phyllodes Tumor of Anogenital Mammary-like Glands with Diffuse Pseudoangiomatous Stromal Hyperplasia

    Directory of Open Access Journals (Sweden)



    Full Text Available Anogenital mammary-like glands may give rise to various pathologic lesions identical to those known in mammary pathology. Tumor occurring in the anogenital region is extremely rare. The histogenetic origin of this tumor is controversial as it is being debated whether such lesions evolve from ectopic breast tissue and most recently, anogenital mammary-like gland. We report a 28-year-old girl who presented with a painless mass in the anogenital region, which was subsequently excised. Microscopic examination revealed morphologic pattern characteristic of benign phyllodes tumor with pseudoangiomatous stromal hyperplasia. We present this case to emphasize the importance of recognizing this uncommon lesion occurring at an extremely unusual site. We also discuss the histogenesis of phyllodes tumor and related lesions occurring in the anogenital region in light of the current literature along with a brief review of the previously reported cases of anogenital mammary-like glands.

  13. Breast Cancer and Early Onset Childhood Obesity: Cell Specific Gene Expression in Mammary Epithelia and Adipocytes

    National Research Council Canada - National Science Library

    Camarillo, Ignacio G; Nichols, Maxine


    ... information exists regarding its association with mammary tumongenesis Towards better understanding this relationship we have developed and characterized a new rat model of childhood onset Diet Induced Obesity (DIO...

  14. On the Sulfation and Methylation of Catecholestrogens in Human Mammary Epithelial Cells and Breast Cancer Cells

    National Research Council Canada - National Science Library

    Hui, Ying; Yasuda, Shin; Liu, Ming-Yih; Wu, Yi-yong; Liu, Ming-Cheh


    .... The present study was designed to examine the role of sulfation in the metabolism of CEs. MCF-7 breast cancer cells and MCF 10A human mammary epithelial cells were metabolically labeled with [35S...

  15. A Cytogenetic Footprint for Mammary Carcinomas Induced by PhIP in Rats

    Energy Technology Data Exchange (ETDEWEB)

    Christian, A T


    PhIP (2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine), a mutagen/carcinogen belonging to the class of heterocyclic amines (HCAs) found in cooked meats, is a mammary gland carcinogen in rats and has been implicated in the etiology of certain human cancers including breast cancer. To gain insight into the genomic alterations associated with PhIP-induced mammary gland carcinogenesis, we used comparative genomic hybridization (CGH) to examine chromosomal abnormalities in rat mammary carcinomas induced by PhIP, and for comparison, by DMBA (7,12-dimethylbenz[a]anthracene), a potent experimental mammary carcinogen. There was a consistent and characteristic pattern of chromosome-region loss in PhIP-induced carcinomas that clearly distinguished them from carcinomas induced by DMBA.

  16. Control of the Mammary Cell Cycle Clock by Estrogen and Progesterone

    National Research Council Canada - National Science Library

    Weinberg, Robert


    Both the growth and the development of the mammary gland are controlled by the female hormones estrogen, prolactin and progesterone, and by interactions between the epithelial and stromal compartments of the breast...

  17. Msx2 Plays a central Role in Regulating Branching Morphogenesis During Mammary Development

    National Research Council Canada - National Science Library

    Liu, Yi-Hsin


    The purpose of this study is to determine the role of a transcriptional factor, Msx2, in regulating branching events in the development of the mouse mammary gland To define the function of Msx2 gene...

  18. Msx2 Plays a Central Role in Regulating Branching Morphogenesis During Mammary Development

    National Research Council Canada - National Science Library

    Liu, Yi-Hsin


    The purpose of this study is to determine the role of a transcriptional factor, Msx2, in regulating initial induction of mammary anlagen and subsequent branching events that may require cooperative...

  19. Processing and characterization of canine mixed mammary tumor using transmission electron microscopy. (United States)

    Audrey, Beltrán; Alexis, Debut; Andrea, Vaca; Julio, Ortiz; Freddy, Proaño-Pérez


    Canine mammary gland tumors represent the second most frequent type of neoplasm in dogs, being an important problem within veterinary medical field. Canine mixed mammary tumors are the most common; the use of a transmission electron microscope (TEM) can contribute as a tool in its diagnosis by determining the characteristics of cellular components from numerous neoplasms. The aim of this study was to characterize cytologically canine mammary mixed tumor by the use of the TEM. A biopsy collected from an 11 years old bitch Shih-Tzu and analyzed by histopathology was used for ultrastructural analysis. Specimens obtained were double stained using uranyl acetate and lead citrate prior to observation in the TEM. The protocol established to transmission electron microscopy observation allowed the identification of main cellular characteristics of canine mixed mammary tumors; however, it was not possible a detailed visualization of the organelles due to the preservation of the biopsy in formaldehyde. © 2017 Wiley Periodicals, Inc.

  20. Secondary Inflammatory Mammary Carcinoma in a Cat? Clinical and Cytological Findings

    Directory of Open Access Journals (Sweden)

    Tuğba Seval Fatma TOYDEMİR


    Full Text Available A case of secondary feline mammary tumor described and discussed with its clinical features similar to inflammatory mammary carcinoma (IMC in this paper. In cats, there were only very few cases of IMC reported until now. A 14-year-old, longhaired female cat was presented to the clinic for the rapid onset of erythema, local pain and warmth of the inguinal region, with a mild exudative haemorrhagic-ulcereted lesion in association with a good-defined underlying mass. The cat had bilateral mastectomy surgery four years ago. Cytological findings were highly associated with inflammatory mammary carcinoma. Due to diffuse pulmonary metastases of the cat surgery could not be suggested as a treatment. In conclusion 1 feline IMC could be useful as an animal model of human inflammatory breast cancer 2 mammary cancer patients should be approached cautiously after even bilaterally performed mastectomy surgeries.

  1. Unique expression pattern of the three insulin receptor family members in the rat mammary gland

    DEFF Research Database (Denmark)

    Hvid, Henning; Klopfleisch, Robert; Vienberg, Sara Gry


    Supra-pharmacological doses of the insulin analog X10 (AspB10) increased the incidence of mammary tumors in female Sprague-Dawley rats in chronic toxicity studies, most likely via receptor-mediated mechanisms. However, little is known about the expression of the insulin receptor family in the rat...... mammary gland. Using laser micro-dissection, quantitative RT-PCR and immunohistochemistry, we examined the expression of IR (insulin receptor), IGF-1R (IGF-1 receptor), IRR (insulin receptor-related receptor), ERα (estrogen receptor alpha), ERβ (estrogen receptor beta) and PR (progesteron receptor......) in young, virgin, female Sprague-Dawley rats and compared to expression in reference organs. The mammary gland displayed the highest expression of IRR and IGF-1R. In contrast, low expression of IR transcripts was observed in the mammary gland tissue with expression of the IR-A isoform being 5-fold higher...

  2. EGF Regulation of VEGF: Role in Progression of ErbB2 Overexpressing Mammary Tumors

    National Research Council Canada - National Science Library

    Loureiro, Robyn


    .... ErbB2, an epidermal growth factor receptor family member whose overexpression in mammary tumors is correlated with poor patient prognosis, has been previously implicated as a positive modulator of VEGF expression...

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

    National Research Council Canada - National Science Library

    Nagy, Tamas


    .... Since our original plan was to inhibit the activities of FAK indirectly using its inhibitor, FIP200, I decided to directly delete FAK in the mammary epithelium of mice employing the Cre-loxP method...

  4. Extensive expression of craniofacial related homeobox genes in canine mammary sarcomas

    NARCIS (Netherlands)

    Wensman, H.; Goransson, H.; Leuchowius, K.J.; Stromberg, S.; Ponten, F.; Isaksson, A.; Rutteman, G.R.|info:eu-repo/dai/nl/074076663; Heldin, N.; Pejler, G.; Hellmen, E.


    Extensive expression of craniofacial related homeobox genes in canine mammary sarcomas Journal Breast Cancer Research and Treatment Publisher Springer Netherlands ISSN 0167-6806 (Print) 1573-7217 (Online) Issue Volume 118, Number 2 / November, 2009 Category Preclinical Study DOI

  5. Expression of Novel Steroid/Receptors in Mammary Development: Peroxisome Proliferator Activated Receptors

    National Research Council Canada - National Science Library

    Gimble, Jeffrey


    ...) are expressed in the mammary gland and regulated during physiologic and pathologic events. The PPARs are nuclear hormone receptors which bind to fatty acids as ligands and control transcription of lipid metabolic genes...

  6. Abomasal protein infusion in postpartum transition dairy cows: Effect on performance and mammary metabolism

    DEFF Research Database (Denmark)

    Larsen, Mogens; Lapierre, H; Kristensen, Niels Bastian


    The effect of increasing the postpartum metabolizable protein (MP) supply on performance and mammary metabolism was studied using 8 Holstein cows in a complete randomized design. At parturition, cows were assigned to abomasal infusion of water (CTRL) or casein (CAS). Arterial and epigastric venous...... blood samples were taken 14 d before expected parturition and at 4, 15, and 29 d in milk (DIM). To compensate previously estimated deficiency of essential AA and to avoid oversupply, casein protein infusion was graduated with 696 ± 1, 490 ± 9, and 212 ± 10 g/d at 4, 15 and 29 DIM, respectively. Dry...... indicated that Lys, Leu, and Tyr were the first-limiting AA at 4 DIM with CTRL. Mammary plasma flow was unaffected by treatment, indicating similar perfusion of mammary tissue. The greater milk yield with CAS was associated with greater mammary uptake of individual essential AA, tendencies to greater uptake...

  7. Genotype x diet interactions in mice predisposed to mammary cancer: II. Tumors and metastasis

    DEFF Research Database (Denmark)

    Gordon, Ryan R; Hunter, Kent W; Merrill, Michele La


    High dietary fat intake and obesity may increase the risk of susceptibility to certain forms of cancer. To study the interactions of dietary fat, obesity, and metastatic mammary cancer, we created a population of F2 mice cosegregating obesity QTL and the MMTV-PyMT transgene. We fed the F2 mice...... effects of diet on mammary tumor and metastases phenotypes, mapping of tumor/metastasis modifier genes, and the interaction between dietary fat levels and effects of cancer modifiers. Results demonstrate that animals fed a high-fat diet are not only more likely to experience decreased mammary cancer...... latency but increased tumor growth and pulmonary metastases occurrence over an equivalent time. We identified 25 modifier loci for mammary cancer and pulmonary metastasis, likely representing 13 unique loci after accounting for pleiotropy, and novel QTL × diet interactions at a majority of these loci...

  8. Unlocking the milk protein gene loci during mammary gland development and differentiation; a role for chromatin (United States)

    Mammary gland development and differentiation occur mostly postnatally. Chromatin organization plays a key role in transcriptional and epigenetic regulation during development and differentiation. Considerable knowledge of the systemic hormones and local growth factors important for development and ...

  9. Luminol-based bioluminescence imaging of mouse mammary tumors. (United States)

    Alshetaiwi, Hamad S; Balivada, Sivasai; Shrestha, Tej B; Pyle, Marla; Basel, Matthew T; Bossmann, Stefan H; Troyer, Deryl L


    Polymorphonuclear neutrophils (PMNs) are the most abundant circulating blood leukocytes. They are part of the innate immune system and provide a first line of defense by migrating toward areas of inflammation in response to chemical signals released from the site. Some solid tumors, such as breast cancer, also cause recruitment and activation of PMNs and release of myeloperoxidase. In this study, we demonstrate that administration of luminol to mice that have been transplanted with 4T1 mammary tumor cells permits the detection of myeloperoxidase activity, and consequently, the location of the tumor. Luminol allowed detection of activated PMNs only two days after cancer cell transplantation, even though tumors were not yet palpable. In conclusion, luminol-bioluminescence imaging (BLI) can provide a pathway towards detection of solid tumors at an early stage in preclinical tumor models. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Refractive index of carcinogen-induced rat mammary tumours (United States)

    Zysk, Adam M.; Chaney, Eric J.; Boppart, Stephen A.


    Near-infrared optical techniques for clinical breast cancer screening in humans are rapidly advancing. Based on the computational inversion of the photon diffusion process through the breast, these techniques rely on optical tissue models for accurate image reconstruction. Recent interest has surfaced regarding the effect of refractive index variations on these reconstructions. Although many data exist regarding the scattering and absorption properties of normal and diseased tissue, no measurements of refractive index appear in the literature. In this paper, we present near-infrared refractive index data acquired from N-methyl-N-nitrosourea-induced rat mammary tumours, which are similar in pathology and disease progression to human ductal carcinoma. Eight animals, including one control, were employed in this study, yielding data from 32 tumours as well as adjacent adipose and connective tissues.

  11. Staged Management of a Ruptured Internal Mammary Artery Aneurysm

    Directory of Open Access Journals (Sweden)

    O Young Kwon


    Full Text Available The rupture of an internal mammary artery (IMA aneurysm in a patient with type 1 neurofibromatosis (NF-1 is a rare but life-threatening complication requiring emergency management. A 50-year-old man with NF-1 was transferred to the emergency department of Kyungpook National University Hospital, where an IMA aneurysmal rupture and hemothorax were diagnosed and drained. The IMA aneurysmal rupture and hemothorax were successfully repaired by staged management combining endovascular treatment and subsequent video-assisted thoracoscopic surgery (VATS. The patient required cardiopulmonary cerebral resuscitation, the staged management of coil embolization, and a subsequent VATS procedure. This staged approach may be an effective therapeutic strategy in cases of IMA aneurysmal rupture.

  12. Mammary analog secretory carcinoma of thyroid: A case report. (United States)

    Rupp, Aaron P; Bocklage, Thèrése J


    Mammary analog secretory carcinoma (MASC) is a recently described rare neoplasm that was first reported in the salivary gland with an associated ETV6-NTRK3 fusion. We present a case of MASC involving and presumably arising in the thyroid, which was originally diagnosed as papillary thyroid carcinoma on fine needle aspiration and surgical resection. The later correct diagnosis of MASC was confirmed by immunohistochemistry and molecular studies. The cytopathological features of MASC in the salivary gland are previously described; however, we present the first cytopathological description of MASC arising in the thyroid with the unique feature of prominent nuclear grooves. Differentiating MASC from overlapping features of cytopathologic mimics such as papillary thyroid carcinoma may carry crucial therapeutic implications. Diagn. Cytopathol. 2017;45:45-50. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Functional development of the adult ovine mammary gland--insights from gene expression profiling. (United States)

    Paten, Amy M; Duncan, Elizabeth J; Pain, Sarah J; Peterson, Sam W; Kenyon, Paul R; Blair, Hugh T; Dearden, Peter K


    The mammary gland is a dynamic organ that undergoes dramatic physiological adaptations during the transition from late pregnancy to lactation. Investigation of the molecular basis of mammary development and function will provide fundamental insights into tissue remodelling as well as a better understanding of milk production and mammary disease. This is important to livestock production systems and human health. Here we use RNA-seq to identify differences in gene expression in the ovine mammary gland between late pregnancy and lactation. Between late pregnancy (135 days of gestation ± 2.4 SD) and lactation (15 days post partum ± 1.27 SD) 13 % of genes in the sheep genome were differentially expressed in the ovine mammary gland. In late pregnancy, cell proliferation, beta-oxidation of fatty acids and translation were identified as key biological processes. During lactation, high levels of milk fat synthesis were mirrored by enrichment of genes associated with fatty acid biosynthesis, transport and lipogenesis. Protein processing in the endoplasmic reticulum was enriched during lactation, likely in support of active milk protein synthesis. Hormone and growth factor signalling and activation of signal transduction pathways, including the JAK-STAT and PPAR pathways, were also differently regulated, indicating key roles for these pathways in functional development of the ovine mammary gland. Changes in the expression of epigenetic regulators, particularly chromatin remodellers, indicate a possible role in coordinating the large-scale transcriptional changes that appear to be required to switch mammary processes from growth and development during late pregnancy to synthesis and secretion of milk during lactation. Coordinated transcriptional regulation of large numbers of genes is required to switch between mammary tissue establishment during late pregnancy, and activation and maintenance of milk production during lactation. Our findings indicate the remarkable

  14. Direct Laser Acceleration in Laser Wakefield Accelerators (United States)

    Shaw, J. L.; Froula, D. H.; Marsh, K. A.; Joshi, C.; Lemos, N.


    The direct laser acceleration (DLA) of electrons in a laser wakefield accelerator (LWFA) has been investigated. We show that when there is a significant overlap between the drive laser and the trapped electrons in a LWFA cavity, the accelerating electrons can gain energy from the DLA mechanism in addition to LWFA. The properties of the electron beams produced in a LWFA, where the electrons are injected by ionization injection, have been investigated using particle-in-cell (PIC) code simulations. Particle tracking was used to demonstrate the presence of DLA in LWFA. Further PIC simulations comparing LWFA with and without DLA show that the presence of DLA can lead to electron beams that have maximum energies that exceed the estimates given by the theory for the ideal blowout regime. The magnitude of the contribution of DLA to the energy gained by the electron was found to be on the order of the LWFA contribution. The presence of DLA in a LWFA can also lead to enhanced betatron oscillation amplitudes and increased divergence in the direction of the laser polarization. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under Award Number DE-NA0001944.

  15. Bovine Mammary Gene Expression Profiling during the Onset of Lactation (United States)

    Gao, Yuanyuan; Lin, Xueyan; Shi, Kerong; Yan, Zhengui; Wang, Zhonghua


    Background Lactogenesis includes two stages. Stage I begins a few weeks before parturition. Stage II is initiated around the time of parturition and extends for several days afterwards. Methodology/Principal Findings To better understand the molecular events underlying these changes, genome-wide gene expression profiling was conducted using digital gene expression (DGE) on bovine mammary tissue at three time points (on approximately day 35 before parturition (−35 d), day 7 before parturition (−7 d) and day 3 after parturition (+3 d)). Approximately 6.2 million (M), 5.8 million (M) and 6.1 million (M) 21-nt cDNA tags were sequenced in the three cDNA libraries (−35 d, −7 d and +3 d), respectively. After aligning to the reference sequences, the three cDNA libraries included 8,662, 8,363 and 8,359 genes, respectively. With a fold change cutoff criteria of ≥2 or ≤−2 and a false discovery rate (FDR) of ≤0.001, a total of 812 genes were significantly differentially expressed at −7 d compared with −35 d (stage I). Gene ontology analysis showed that those significantly differentially expressed genes were mainly associated with cell cycle, lipid metabolism, immune response and biological adhesion. A total of 1,189 genes were significantly differentially expressed at +3 d compared with −7 d (stage II), and these genes were mainly associated with the immune response and cell cycle. Moreover, there were 1,672 genes significantly differentially expressed at +3 d compared with −35 d. Gene ontology analysis showed that the main differentially expressed genes were those associated with metabolic processes. Conclusions The results suggest that the mammary gland begins to lactate not only by a gain of function but also by a broad suppression of function to effectively push most of the cell's resources towards lactation. PMID:23990904

  16. Bovine mammary gene expression profiling during the onset of lactation.

    Directory of Open Access Journals (Sweden)

    Yuanyuan Gao

    Full Text Available BACKGROUND: Lactogenesis includes two stages. Stage I begins a few weeks before parturition. Stage II is initiated around the time of parturition and extends for several days afterwards. METHODOLOGY/PRINCIPAL FINDINGS: To better understand the molecular events underlying these changes, genome-wide gene expression profiling was conducted using digital gene expression (DGE on bovine mammary tissue at three time points (on approximately day 35 before parturition (-35 d, day 7 before parturition (-7 d and day 3 after parturition (+3 d. Approximately 6.2 million (M, 5.8 million (M and 6.1 million (M 21-nt cDNA tags were sequenced in the three cDNA libraries (-35 d, -7 d and +3 d, respectively. After aligning to the reference sequences, the three cDNA libraries included 8,662, 8,363 and 8,359 genes, respectively. With a fold change cutoff criteria of ≥ 2 or ≤-2 and a false discovery rate (FDR of ≤ 0.001, a total of 812 genes were significantly differentially expressed at -7 d compared with -35 d (stage I. Gene ontology analysis showed that those significantly differentially expressed genes were mainly associated with cell cycle, lipid metabolism, immune response and biological adhesion. A total of 1,189 genes were significantly differentially expressed at +3 d compared with -7 d (stage II, and these genes were mainly associated with the immune response and cell cycle. Moreover, there were 1,672 genes significantly differentially expressed at +3 d compared with -35 d. Gene ontology analysis showed that the main differentially expressed genes were those associated with metabolic processes. CONCLUSIONS: The results suggest that the mammary gland begins to lactate not only by a gain of function but also by a broad suppression of function to effectively push most of the cell's resources towards lactation.

  17. Inhibition of rat mammary tumorigenesis by dietary cholesterol. (United States)

    el-Sohemy, A; Bruce, W R; Archer, M C


    The effects of dietary cholesterol and oxidized cholesterol on mammary tumor development were examined in female Sprague-Dawley rats exposed to the carcinogen N-methyl-N-nitrosourea (MNU). Animals were administered 50 mg/kg MNU at 50 days of age and fed either a control (AIN-76) diet or the control diet supplemented with 0.3% cholesterol or 0.3% oxidized cholesterol for up to 26 weeks. The oxidized cholesterol was prepared by heating cholesterol at 110 degrees C for 48 h. Gas chromatographic analysis of the oxidized cholesterol revealed a 2% yield of oxidation products in addition to a large amount of unchanged cholesterol (> 96%). Tumor incidence in the cholesterol group (67%) was significantly lower than in the control group (96%, P < 0.05), but the oxidized cholesterol group (79%) was not significantly different from the control or cholesterol groups. Average number of tumors per animal was lower in the cholesterol group (1.5) than in the control (2.8) or oxidized cholesterol groups (2.3, P < 0.005). Serum low density lipoprotein (LDL) cholesterol was greater in the cholesterol (185 +/- 38 mg/dl) and the oxidized cholesterol groups (160 +/- 34 mg/dl) than in the controls (55 +/- 4 mg/dl, P < 0.05), although there was no difference between the cholesterol and the oxidized cholesterol groups. These results show that dietary cholesterol inhibits mammary tumor development in this model. Elevated serum LDL cholesterol may inhibit de novo cholesterol synthesis in preneoplastic and/or tumor cells, thereby inhibiting their proliferation.

  18. Pericentriolar Targeting of the Mouse Mammary Tumor Virus GAG Protein.

    Directory of Open Access Journals (Sweden)

    Guangzhi Zhang

    Full Text Available The Gag protein of the mouse mammary tumor virus (MMTV is the chief determinant of subcellular targeting. Electron microscopy studies show that MMTV Gag forms capsids within the cytoplasm and assembles as immature particles with MMTV RNA and the Y box binding protein-1, required for centrosome maturation. Other betaretroviruses, such as Mason-Pfizer monkey retrovirus (M-PMV, assemble adjacent to the pericentriolar region because of a cytoplasmic targeting and retention signal in the Matrix protein. Previous studies suggest that the MMTV Matrix protein may also harbor a similar cytoplasmic targeting and retention signal. Herein, we show that a substantial fraction of MMTV Gag localizes to the pericentriolar region. This was observed in HEK293T, HeLa human cell lines and the mouse derived NMuMG mammary gland cells. Moreover, MMTV capsids were observed adjacent to centrioles when expressed from plasmids encoding either MMTV Gag alone, Gag-Pro-Pol or full-length virus. We found that the cytoplasmic targeting and retention signal in the MMTV Matrix protein was sufficient for pericentriolar targeting, whereas mutation of the glutamine to alanine at position 56 (D56/A resulted in plasma membrane localization, similar to previous observations from mutational studies of M-PMV Gag. Furthermore, transmission electron microscopy studies showed that MMTV capsids accumulate around centrioles suggesting that, similar to M-PMV, the pericentriolar region may be a site for MMTV assembly. Together, the data imply that MMTV Gag targets the pericentriolar region as a result of the MMTV cytoplasmic targeting and retention signal, possibly aided by the Y box protein-1 required for the assembly of centrosomal microtubules.

  19. RF linear accelerators

    CERN Document Server

    Wangler, Thomas P


    Thomas P. Wangler received his B.S. degree in physics from Michigan State University, and his Ph.D. degree in physics and astronomy from the University of Wisconsin. After postdoctoral appointments at the University of Wisconsin and Brookhaven National Laboratory, he joined the staff of Argonne National Laboratory in 1966, working in the fields of experimental high-energy physics and accelerator physics. He joined the Accelerator Technology Division at Los Alamos National Laboratory in 1979, where he specialized in high-current beam physics and linear accelerator design and technology. In 2007

  20. Confronting Twin Paradox Acceleration (United States)

    Murphy, Thomas W.


    The resolution to the classic twin paradox in special relativity rests on the asymmetry of acceleration. Yet most students are not exposed to a satisfactory analysis of what exactly happens during the acceleration phase that results in the nonaccelerated observer's more rapid aging. The simple treatment presented here offers both graphical and quantitative solutions to the problem, leading to the correct result that the acceleration-induced age gap is 2Lβ years when the one-way distance L is expressed in light-years and velocity β ≡v/c .

  1. Accelerator Production of Radionuclides (United States)

    Schlyer, David J.; Ruth, Thomas J.


    While many radioactive isotopes in use today are found in nature, many more are artificially produced by irradiating target materials with nuclear particles. Two different technologies can provide the energetic particles needed: nuclear reactors, which produce a flux of neutrons, and particle accelerators, which produce a flux of charged particles. This chapter will deal with the important aspects of the production of radionuclides with accelerators, along with some details on their applications, commercially-available accelerator systems used for this purpose, and the size of the equipment business.

  2. The Influence of Stromal Transforming Growth Factor-Beta Receptor Signaling on Mouse Mammary Neoplasia (United States)


    AD Award Number: DAMD17-01-1-0201 TITLE: The Influence of Stromal Transforming Growth Factor-r Receptor Signaling on Mouse Mammary Neoplasia ...SUBTITLE 5. FUNDING NUMBERS The Influence of Stromal Transforming Growth Factor-P DAMD17-01-1-0201 Receptor Signaling on Mouse Mammary Neoplasia 6. AUTHOR...stromal fibroblasts resulted in the appearance of intraepithelial neoplasia (10). These results suggest that TGF-P signaling in the stroma and epithelium is

  3. Engineering of Specific Tissue Inhibitors to Block ADAM Type Metalloprotease-Mediated Mammary Neoplasia (United States)


    Mediated Mammary Neoplasia PRINCIPAL INVESTIGATOR: Yibing Yan, Ph.D. Z. Werb, Ph.D. CONTRACTING ORGANIZATION: University of California San Francisco San...Inhibitors to Block ADAM Type DAMD17-98-l-8193 Metalloprotease-Mediated Mammary Neoplasia 6. AUTHOR(S) Yibing Yan, Ph.D. Z. Werb, Ph.D. 7. PERFORMING...cell transformation. Therefore, targeting the matrix metalloprotease mKUZ may prevent early neoplasia . 14. SUBJECT TERMS 15. NUWR"R OF PAGES Breast

  4. Efficacy of fine needle aspiration in the diagnosis of spontaneous mammary tumors


    Colodel, Marcia Moleta [UNESP; Ferreira,Isabelle; Figueiroa, Fernanda Carmello [UNESP; Rocha, Noeme Sousa


    The cytopathology exam has been utilized to diagnose mammary disorders in female dogs. The success of cytopathology results depends on, among other factors, the diagnostic accuracy of the exam. The present study aimed to compare the cytopathological and histopathological findings from mammary disorder cases in female dogs and evaluate the lesion cytopathology exam accuracy. The concordance degree was evaluated between the cytopathology and histopathology exams of 67 female dogs, carriers of p...

  5. Calcarea carbonica derivative complex (M8) as adjuvant treatment of inflammatory mammary carcinoma in a dog


    Simone Domit Guérios; Carolina Camargo de Oliveira; Daniella Matos da Silva; Eneida Janiscki Da Lozzo; Dorly de Freitas Buchi


    Background: Inflammatory mammary carcinoma (IMC) is locally aggressive, fast growing, highly malignant tumor that affects humans and dogs. Affected dogs usually are presented with generalized edema, pain, erythema, and skin ulceration in mammary glands. Surgery is not recommended and an effective treatment has not been established [1]. Calcarea carbonica derivative complex (M8) has demonstrated anticancer properties in a murine model, by improving innate immune response against tumor cells [2...

  6. The assessment of the prevalence of associated benign pathology of thyroid and mammary glands




    Objective: to assess the prevalence of associated benign pathology of thyroid and mammary glands in women with unsuppressed menstrual cycle. Materials and methods: 265 women with unsuppressed menstrual cycle (MC) were examined by the sample method. The examination of the women included ultrasonography of thyroid and mammary glands with the detector-frequency of 7.5 MHz. The thyroid status and clinicolaboratory indicators of the reproductive system were estimated. Results. The prevalence of th...

  7. Oncogene-Induced Changes in Mammary Cell Fate and EMT in Breast Tumorigenesis (United States)


    Snail shRNA (n=125) b. Serial dilution injection into NOD SCID mammary glands with weekly palpation This task is to test the in-vivo tumor initiating...Subaim1a d. Serial dilution injection into NOD SCID mammary glands with weekly palpation As stated above, the HMEC cells are ready and testing has begun...experimental techniques . These optimization experiments are all outlined below. As demonstrated in Aim 1b, we have successfully cloned CD8IGF1R into

  8. The Possible Role of E2F in Rat Mammary Carcinogenesis (United States)


    activity in cancer , I have used two model systems: a rat mammary tumor assay and an NIH 3T3 focus formation assay. While the rat mammary study did not...inhibitory effects of EMF and E2F3. I am currently investigating if E2F can inhibit transformation mediated by oncogenes other than the ras oncogene. 14...SUBJECT TERMS Breast Cancer 15. NUMBER OF PAGES 13 E2F transcription factors, ras, oncogene, transformation, _________ growth inhibition, NIH 3T3

  9. Comparative study of the influence of pregnancy and hormonal treatment on mammary carcinogenesis.


    Russo, I. H.; Koszalka, M.; Russo, J


    Since it has been shown that pregnancy protects the mammary gland from chemically induced carcinogenesis, this study was designed with the dual purpose of determining whether treatment of young virgin rats with the placental hormone chorionic gonadotropin (hCG) mimics pregnancy-induced changes in the tumourigenic response of the mammary gland and also whether the effect induced by both pregnancy and hormonal treatments was transitory, or a more permanent one, exerting the same effect when the...

  10. Characterisation of microRNA expression in post-natal mouse mammary gland development

    Directory of Open Access Journals (Sweden)

    Karagavriilidou Konstantina


    Full Text Available Abstract Background The differential expression pattern of microRNAs (miRNAs during mammary gland development might provide insights into their role in regulating the homeostasis of the mammary epithelium. Our aim was to analyse these regulatory functions by deriving a comprehensive tissue-specific combined miRNA and mRNA expression profile of post-natal mouse mammary gland development. We measured the expression of 318 individual murine miRNAs by bead-based flow-cytometric profiling of whole mouse mammary glands throughout a 16-point developmental time course, including juvenile, puberty, mature virgin, gestation, lactation, and involution stages. In parallel whole-genome mRNA expression data were obtained. Results One third (n = 102 of all murine miRNAs analysed were detected during mammary gland development. MicroRNAs were represented in seven temporally co-expressed clusters, which were enriched for both miRNAs belonging to the same family and breast cancer-associated miRNAs. Global miRNA and mRNA expression was significantly reduced during lactation and the early stages of involution after weaning. For most detected miRNA families we did not observe systematic changes in the expression of predicted targets. For miRNA families whose targets did show changes, we observed inverse patterns of miRNA and target expression. The data sets are made publicly available and the combined expression profiles represent an important community resource for mammary gland biology research. Conclusion MicroRNAs were expressed in likely co-regulated clusters during mammary gland development. Breast cancer-associated miRNAs were significantly enriched in these clusters. The mechanism and functional consequences of this miRNA co-regulation provide new avenues for research into mammary gland biology and generate candidates for functional validation.

  11. An Immunohistochemical study of HER-2 expression in feline mammary tumours. (United States)

    Rasotto, R; Caliari, D; Castagnaro, M; Zanetti, R; Zappulli, V


    The aim of the present study was to evaluate HER-2 expression in feline mammary tumours. Five different immunohistochemical protocols were tested with 73 feline mammary carcinomas (MCs), 10 mammary adenomas and 73 hyperplastic or dysplastic mammary lesions. The histological features of these lesions, clinical follow-up and expression of Ki-67 and p53 were also examined. With an optimized immunohistochemical protocol, HER-2 overexpression was detected in only four of the 73 (5.5%) MCs and did not correlate with histological classification or with the 1 year post-surgical clinical outcome. No correlation was found between the expression of Ki-67 or p53 and HER-2. Five of the 73 (6.8%) hyperplastic or dysplastic lesions and one of the 10 (10%) mammary adenomas were HER-2 positive. These results suggest that HER-2 may not play as significant role in mammary carcinogenesis and prognosis in cats as it does in human patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. The Wnt co-receptor Lrp6 is required for normal mouse mammary gland development.

    Directory of Open Access Journals (Sweden)

    Charlotta Lindvall

    Full Text Available Canonical Wnt signals are transduced through a Frizzled receptor and either the LRP5 or LRP6 co-receptor; such signals play central roles during development and in disease. We have previously shown that Lrp5 is required for ductal stem cell activity and that loss of Lrp5 delays normal mammary development and Wnt1-induced tumorigenesis. Here we show that canonical Wnt signals through the Lrp6 co-receptor are also required for normal mouse mammary gland development. Loss of Lrp6 compromises Wnt/beta-catenin signaling and interferes with mammary placode, fat pad, and branching development during embryogenesis. Heterozygosity for an inactivating mutation in Lrp6 is associated with a reduced number of terminal end buds and branches during postnatal development. While Lrp6 is expressed in both the basal and luminal mammary epithelium during embryogenesis, Lrp6 expression later becomes restricted to cells residing in the basal epithelial layer. Interestingly, these cells also express mammary stem cell markers. In humans, increased Lrp6 expression is associated with basal-like breast cancer. Taken together, our results suggest both overlapping and specific functions for Lrp5 and Lrp6 in the mammary gland.

  13. Redefining the expression and function of the inhibitor of differentiation 1 in mammary gland development.

    Directory of Open Access Journals (Sweden)

    Radhika Nair


    Full Text Available The accumulation of poorly differentiated cells is a hallmark of breast neoplasia and progression. Thus an understanding of the factors controlling mammary differentiation is critical to a proper understanding of breast tumourigenesis. The Inhibitor of Differentiation 1 (Id1 protein has well documented roles in the control of mammary epithelial differentiation and proliferation in vitro and breast cancer progression in vivo. However, it has not been determined whether Id1 expression is sufficient for the inhibition of mammary epithelial differentiation or the promotion of neoplastic transformation in vivo. We now show that Id1 is not commonly expressed by the luminal mammary epithelia, as previously reported. Generation and analysis of a transgenic mouse model of Id1 overexpression in the mammary gland reveals that Id1 is insufficient for neoplastic progression in virgin animals or to prevent terminal differentiation of the luminal epithelia during pregnancy and lactation. Together, these data demonstrate that there is no luminal cell-autonomous role for Id1 in mammary epithelial cell fate determination, ductal morphogenesis and terminal differentiation.

  14. Identification of stable and oestrus cycle-independent housekeeping genes in the rat mammary gland and other tissues

    DEFF Research Database (Denmark)

    Hvid, Henning; Ekstrøm, Claus T; Vienberg, Sara Gry


    The function and development of the rat mammary gland is dependent on the oestrus cycle. Normalization of gene expression in mammary gland samples assessed by quantitative RT-PCR therefore requires housekeeping genes (HKGs) which are stably expressed during the oestrus cycle. mRNA expression of 10...... HKGs was measured in the rat mammary gland at different phases of the oestrus cycle. In addition, mRNA expression of the HKGs was measured in a panel of other rat tissues comprising laser microdissected mammary gland alveolar lobules and interlobular connective tissue and macrodissected mammary gland......, liver, skeletal muscle, colon and ovary samples. Expression and ranking of HKGs varied between tissues and oestrus cycle phases and several HKGs were necessary for normalization between samples. In the mammary gland samples, three HKGs (Sdha, Tbp, and Atp5b) were identified as the optimal combination...

  15. Non-accelerator experiments

    Energy Technology Data Exchange (ETDEWEB)

    Goldhaber, M.


    This report discusses several topics which can be investigated without the use of accelerators. Topics covered are: (1) proton decay, (2) atmospheric neutrinos, (3) neutrino detection, (4) muons from Cygnus X-3, and (5) the double-beta decay.

  16. Macromolecular ion accelerator. (United States)

    Hsu, Yun-Fei; Lin, Jung-Lee; Lai, Szu-Hsueh; Chu, Ming-Lee; Wang, Yi-Sheng; Chen, Chung-Hsuan


    Presented herein are the development of macromolecular ion accelerator (MIA) and the results obtained by MIA. This new instrument utilizes a consecutive series of planar electrodes for the purpose of facilitating stepwise acceleration. Matrix-assisted laser desorption/ionization (MALDI) is employed to generate singly charged macromolecular ions. A regular Z-gap microchannel plate (MCP) detector is mounted at the end of the accelerator to record the ion signals. In this work, we demonstrated the detection of ions with the mass-to-charge (m/z) ratio reaching 30,000,000. Moreover, we showed that singly charged biomolecular ions can be accelerated with the voltage approaching 1 MV, offering the evidence that macromolecular ions can possess much higher kinetic energy than ever before.

  17. The next big accelerator

    CERN Multimedia

    Cramer, J G


    Accelerator physics in the US has been devastated by the cancellation of two high-energy physics colliders facilities. However there are future plans. A suggestion is made to build the new collider in the Australian outback.

  18. Accelerated learning in Afghanistan

    Directory of Open Access Journals (Sweden)

    Christine Capacci Carneal


    Full Text Available Most accelerated learning (AL programmes are ‘catch up’ initiatives to assist out-of-school youth into formal education. But what happens when adults join and complete AL classes?


    Energy Technology Data Exchange (ETDEWEB)

    Sampayan, S; Caporaso, G; Chen, Y; Harris, J; Hawkins, S; Holmes, C; Nelson, S; Poole, B; Rhodes, M; Sanders, D; Sullivan, J; Wang, L; Watson, J


    The dielectric wall accelerator (DWA) is a compact pulsed power device where the pulse forming lines, switching, and vacuum wall are integrated into a single compact geometry. For this effort, we initiated a extensive compact pulsed power development program and have pursued the study of switching (gas, oil, laser induced surface flashover and photoconductive), dielectrics (ceramics and nanoparticle composites), pulse forming line topologies (asymmetric and symmetric Blumleins and zero integral pulse forming lines), and multilayered vacuum insulator (HGI) technology. Finally, we fabricated an accelerator cell for test on ETAII (a 5.5 MeV, 2 kA, 70 ns pulsewidth electron beam accelerator). We review our past results and report on the progress of accelerator cell testing.

  20. Rejuvenating CERN's Accelerators

    CERN Multimedia


    In the coming years and especially in 2005, CERN's accelerators are going to receive an extensive renovation programme to ensure they will perform reliably and effectively when the LHC comes into service.

  1. SPS accelerating cavity

    CERN Multimedia

    CERN PhotoLab


    View towards the downstream end of one of the SPS accelerating cavities (200 MHz, travelling wave structure). See 7603195 and 8011289 for more details, 7411032 for the travelling wave structure, and also 8104138.

  2. Linear Accelerator (LINAC) (United States)

    ... View full size with caption Related Articles and Media External Beam Therapy (EBT) Intensity-Modulated Radiation Therapy (IMRT) Image-guided Radiation Therapy (IGRT) Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiotherapy (SBRT) Images related to Linear Accelerator Sponsored ...

  3. Joint International Accelerator School

    CERN Multimedia

    CERN Accelerator School


    The CERN and US Particle Accelerator Schools recently organised a Joint International Accelerator School on Beam Loss and Accelerator Protection, held at the Hyatt Regency Hotel, Newport Beach, California, USA from 5-14 November 2014. This Joint School was the 13th in a series of such schools, which started in 1985 and also involves the accelerator communities in Japan and Russia.   Photo courtesy of Alfonse Pham, Michigan State University.   The school attracted 58 participants representing 22 different nationalities, with around half from Europe and the other half from Asia and the Americas. The programme comprised 26 lectures, each of 90 minutes, and 13 hours of case study. The students were given homework each day and had an opportunity to sit a final exam, which counted towards university credit. Feedback from the participants was extremely positive, praising the expertise and enthusiasm of the lecturers, as well as the high standard and quality of their lectures. Initial dis...

  4. Amps particle accelerator definition study (United States)

    Sellen, J. M., Jr.


    The Particle Accelerator System of the AMPS (Atmospheric, Magnetospheric, and Plasmas in Space) payload is a series of charged particle accelerators to be flown with the Space Transportation System Shuttle on Spacelab missions. In the configuration presented, the total particle accelerator system consists of an energetic electron beam, an energetic ion accelerator, and both low voltage and high voltage plasma acceleration devices. The Orbiter is illustrated with such a particle accelerator system.

  5. Influence of prevastein (R), an isoflavone-rich soy product, on mammary gland development and Tumorigenesis in Tg.NK (MMTV/c-neu) mice

    DEFF Research Database (Denmark)

    Thomsen, Anni R.; Mortensen, Alicja; Breinholt, Vibeke


    We investigated spontaneous mammary tumor development and mammary gland morphogenesis in female Tg.NK mice postnatally exposed to dietary soy isoflavones (0, 11, 39, and 130 mg aglycones/kg diet) added to a Western-style diet. Instead of preventing mammary tumorigenesis, the highest dose of isofl......We investigated spontaneous mammary tumor development and mammary gland morphogenesis in female Tg.NK mice postnatally exposed to dietary soy isoflavones (0, 11, 39, and 130 mg aglycones/kg diet) added to a Western-style diet. Instead of preventing mammary tumorigenesis, the highest dose...

  6. LHCb GPU Acceleration Project

    CERN Document Server

    AUTHOR|(SzGeCERN)744808; Campora Perez, Daniel Hugo; Neufeld, Niko; Vilasis Cardona, Xavier


    The LHCb detector is due to be upgraded for processing high-luminosity collisions, which will increase the load on its computation infrastructure from 100 GB/s to 4 TB/s, encouraging us to look for new ways of accelerating the Online reconstruction. The Coprocessor Manager is our new framework for integrating LHCb’s existing computation pipelines with massively parallel algorithms running on GPUs and other accelerators. This paper describes the system and analyzes its performance.

  7. Accelerating News Issue 2

    CERN Document Server

    Kahle, K; Wildner, E


    In this summer issue we look at how developments in collimator materials could have applications in aerospace and beyond, and how Polish researchers are harnessing accelerators for medical and industrial uses. We see how the LHC luminosity upgrade is linking with European industry and US researchers, and how the neutrino oscillation community is progressing. We find out the mid-term status of TIARA-PP and how it is mapping European accelerator education resources.

  8. Accelerated Evidence Search Report (United States)


    Accelerated Evidence Search Report IMPORTANT INFORMATIVE STATEMENTS Accelerated Multi-Camera Evidence Search and Retrieval CSSP Project #: CSSP -2013...CD-1063 was supported by the Canadian Safety and Security Program ( CSSP ) which is led by Defence Research and Development Canada’s Centre for...Border Technology Division The CSSP is a federally-funded program to strengthen Canada’s ability to anticipate, prevent/mitigate, prepare for, respond to

  9. Lipoestructura y relleno del polo superior de la mama frente a implantes Structural fat graft and lipofilling of mammary upper pole versus mammary implants

    Directory of Open Access Journals (Sweden)

    J.M. Cervilla Lozano


    Full Text Available La lipoestructura mamaria ofrece nuevas alternativas de tratamiento en la cirugía estética de aumento mamario, cumpliendo en algunos casos las expectativas esperadas y en otros no. Analizamos este hecho en 4 tipos de aplicación de lipoestructura mamaria que hemos venido realizando en los últimos años, centrándonos en un aspecto importante de esta cirugía que es el relleno del polo superior de la mama. Los tipos de aplicación empleados son: aumento mamario simple mediante lipoestructura en comparación con implantes; pexia más lipoestructura frente a pexia más implantes mamarios; reconstrucción de mama tuberosa mediante lipoestructura o implantes y finalmente, relleno periprotésico mediante lipoestructura en mamas sometidas a cirugía de aumento mamario con implantes. En definitiva, podríamos resumir este trabajo en una frase diciendo que la lipoestructura mamaria, a nuestro juicio, no sirve si lo que prima es conseguir el relleno del polo superior de la mama, siendo en este caso de elección la colocación de implantes mamarios. No obstante, en alguno de los casos señalados no solo es una alternativa, sino que obtiene resultados superiores a los logrados sólamente con implantes.The mammary structural fat graft offers news treatment options in breast augmentation cosmetic surgery, but it sometimes meets expectations and sometimes doesn´t. We analyze 4 different types of lipostructure mammary applications that we have been using in the last years, focused in an important aspect of this surgery as it´s the filling of the upper mammary pole. These applications are: mammary augmentation by simple structural fat compared with the use of mammary implants; structural fat graft and mastopexy versus implants and mastopexy; tuberous breast reconstruction using structural fat graft or implants and finally, periprosthetic filling in breast augmentation with mammary implants using structural fat graft. In short, we could summarize this paper

  10. Unexpected severe consequences of Pikfyve deletion by aP2- or Aq-promoter-driven Cre expression for glucose homeostasis and mammary gland development. (United States)

    Ikonomov, Ognian C; Sbrissa, Diego; Delvecchio, Khortnal; Rillema, James A; Shisheva, Assia


    Systemic deficiency of PIKfyve, the evolutionarily conserved phosphoinositide kinase synthesizing cellular PtdIns5P and PtdIns(3,5)P2 and implicated in insulin signaling, causes early embryonic death in mice. In contrast, mice with muscle-specific Pikfyve disruption have normal lifespan but exhibit early-age whole-body glucose intolerance and muscle insulin resistance, thus establishing the key role of muscle PIKfyve in glucose homeostasis. Fat and muscle tissues control postprandial glucose clearance through different mechanisms, raising questions as to whether adipose Pikfyve disruption will also trigger whole-body metabolic abnormalities, and if so, what the mechanism might be. To clarify these issues, here we have characterized two new mouse models with adipose tissue disruption of Pikfyve through Cre recombinase expression driven by adipose-specific aP2- or adiponectin (Aq) promoters. Whereas both mouse lines were ostensibly normal until adulthood, their glucose homeostasis and systemic insulin sensitivity were severely dysregulated. These abnormalities stemmed in part from accelerated fat-cell lipolysis and elevated serum FFA Intriguingly, aP2-Cre-PIKfyve(fl/fl) but not Aq-Cre-PIKfyve(fl/fl) females had severely impaired pregnancy-induced mammary gland differentiation and lactogenesis, consistent with aP2-Cre-mediated Pikfyve excision in nonadipogenic tissues underlying this defect. Intriguingly, whereas mammary glands from postpartum control and Aq-Cre-PIKfyve(fl/fl) mice or ex vivo mammary gland explants showed profound upregulation of PIKfyve protein levels subsequent to prolactin receptor activation, such increases were not apparent in aP2-Cre-PIKfyve(fl/fl) females. Collectively, our data identify for the first time that adipose tissue Pikfyve plays a key role in the mechanisms regulating glucose homeostasis and that the PIKfyve pathway is critical in mammary epithelial differentiation during pregnancy and lactogenesis downstream of prolactin receptor

  11. Time-lapse Imaging of Primary Preneoplastic Mammary Epithelial Cells Derived from Genetically Engineered Mouse Models of Breast Cancer


    Nakles, Rebecca E.; Millman, Sarah L.; Cabrera, M. Carla; Johnson, Peter; Mueller, Susette; Hoppe, Philipp S.; Schroeder, Timm; Furth, Priscilla A.


    Time-lapse imaging can be used to compare behavior of cultured primary preneoplastic mammary epithelial cells derived from different genetically engineered mouse models of breast cancer. For example, time between cell divisions (cell lifetimes), apoptotic cell numbers, evolution of morphological changes, and mechanism of colony formation can be quantified and compared in cells carrying specific genetic lesions. Primary mammary epithelial cell cultures are generated from mammary glands without...

  12. The Role of BRCA1 in Suppressing Epithelial-Mesenchymal Transition in Mammary Gland and Tumor Development (United States)


    Histo- and pathological analysis revealed that, unlike homogeneous and well differentiated T47D-Sh-Ctrl. mammary tumors, T47D-Sh-BRCA1 tumors were...AWARD NUMBER: W81XWH-13-1-0282 TITLE: The Role of BRCA1 in Suppressing Epithelial-Mesenchymal Transition in Mammary Gland and Tumor...2014 - 31 Aug 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER The Role of BRCA1 in Suppressing Epithelial-Mesenchymal Transition in Mammary Gland and

  13. Functional Analyse of GLUT1 and GLUT12 in Glucose Uptake in Goat Mammary Gland Epithelial Cells


    Yu, Qinghua; Zhu, Liqi; Lin, Jian; Zhang, Qiang; Tian, Qi; Hu, Weiwei; Yang, Qian


    Glucose transport, mediated by glucose transporters, is necessary for mammary gland development and lactation. GLUT1 and GLUT12 could both be expressed in the pregnant and lactating mammary gland to participate in the glucose uptake process. In this study, the goat GLUT1 and GLUT12 genes were cloned from Saanen dairy goats and transfected into goat mammary gland epithelial cells to assess their biological functions and distributions. The results showed that both goat GLUT1 and GLUT12 had 12 p...

  14. Prolactin-like activity of anti-prolactin receptor antibodies on casein and DNA synthesis in the mammary gland.


    Djiane, J; Houdebine, L M; Kelly, P A


    Prolactin receptors were partially purified from rabbit mammary gland membranes by using an affinity chromatography technique. Antibodies against this prolactin receptor preparation were obtained in guinea pig and sheep. Both antisera were able to inhibit the binding of 125I-labeled ovine prolactin to rabbit mammary gland membranes. When added to culture media of rabbit mammary explants, the anti-prolactin receptor antiserum inhibited the capacity of prolactin to initiate casein synthesis and...

  15. Loss of EZH2 results in precocious mammary gland development and activation of STAT5-dependent genes (United States)

    Yoo, Kyung Hyun; Oh, Sumin; Kang, Keunsoo; Hensel, Tim; Robinson, Gertraud W.; Hennighausen, Lothar


    Establishment and differentiation of mammary alveoli during pregnancy are controlled by prolactin through the transcription factors STAT5A and STAT5B (STAT5), which also regulate temporal activation of mammary signature genes. This study addressed the question whether the methyltransferase and transcriptional co-activator EZH2 controls the differentiation clock of mammary epithelium. Ablation of Ezh2 from mammary stem cells resulted in precocious differentiation of alveolar epithelium during pregnancy and the activation of mammary-specific STAT5 target genes. This coincided with enhanced occupancy of these loci by STAT5, EZH1 and RNA Pol II. Limited activation of differentiation-specific genes was observed in mammary epithelium lacking both EZH2 and STAT5, suggesting a modulating but not mandatory role for STAT5. Loss of EZH2 did not result in overt changes in genome-wide and gene-specific H3K27me3 profiles, suggesting compensation through enhanced EZH1 recruitment. Differentiated mammary epithelia did not form in the combined absence of EZH1 and EZH2. Transplantation experiments failed to demonstrate a role for EZH2 in the activity of mammary stem and progenitor cells. In summary, while EZH1 and EZH2 serve redundant functions in the establishment of H3K27me3 marks and the formation of mammary alveoli, the presence of EZH2 is required to control progressive differentiation of milk secreting epithelium during pregnancy. PMID:26250110

  16. Small type accelerator. Try for accelerator driven system

    CERN Document Server

    Mori, Y


    FFAG (Fixed-field alternating gradient) accelerator for accelerator driven subcritical reactor, which aims to change from long-lived radioactive waste to short-lived radioactivity, is introduced. It is ring accelerator. The performance needed is proton as accelerator particle, 10MW (total) beam power, about 1GeV beam energy, >30% power efficiency and continuous beam. The feature of FFAG accelerator is constant magnetic field. PoP (Proof-of-principle)-FFAG accelerator, radial type, was run at first in Japan in 2000. The excursion is about some ten cm. In principle, beam can be injected and extracted at any place of ring. The 'multi-fish' acceleration can accelerate beams to 100% duty by repeating acceleration. 150MeV-FFAG accelerator has been started since 2001. It tried to practical use, for example, treatment of cancer. (S.Y.)

  17. Peripheral serotonin regulates maternal calcium trafficking in mammary epithelial cells during lactation in mice.

    Directory of Open Access Journals (Sweden)

    Jimena Laporta

    Full Text Available 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.

  18. Gestational high-fat diet and bisphenol A exposure heightens mammary cancer risk. (United States)

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


    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. © 2017 The authors.

  19. Tocopherols inhibit oxidative and nitrosative stress in estrogen-induced early mammary hyperplasia in ACI rats. (United States)

    Das Gupta, Soumyasri; So, Jae Young; Wall, Brian; Wahler, Joseph; Smolarek, Amanda K; Sae-Tan, Sudathip; Soewono, Kelvin Y; Yu, Haixiang; Lee, Mao-Jung; Thomas, Paul E; Yang, Chung S; Suh, Nanjoo


    Oxidative stress is known to play a key role in estrogen-induced breast cancer. This study assessed the chemopreventive activity of the naturally occurring γ-tocopherol-rich mixture of tocopherols (γ-TmT) in early stages of estrogen-induced mammary hyperplasia in ACI rats. ACI rats provide an established model of rodent mammary carcinogenesis due to their high sensitivity to estrogen. Female rats were implanted with 9 mg of 17β-estradiol (E2) in silastic tubings and fed with control or 0.3% γ-TmT diet for 1, 3, 7, and 14 d. γ-TmT increased the levels of tocopherols and their metabolites in the serum and mammary glands of the rats. Histological analysis revealed mammary hyperplasia in the E2 treated rats fed with control or γ-TmT diet. γ-TmT decreased the levels of E2-induced nitrosative and oxidative stress markers, nitrotyrosine, and 8-oxo-dG, respectively, in the hyperplastic mammary tissues. 8-Isoprostane, a marker of oxidative stress in the serum, was also reduced by γ-TmT. Noticeably, γ-TmT stimulated Nrf2-dependent antioxidant response in the mammary glands of E2 treated rats, evident from the induced mRNA levels of Nrf2 and its downstream antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase. Therefore, inhibition of nitrosative/oxidative stress through induction of antioxidant response is the primary effect of γ-TmT in early stages of E2-induced mammary hyperplasia. Due to its cytoprotective activity, γ-TmT could be a potential natural agent for the chemoprevention of estrogen-induced breast cancer. © 2014 Wiley Periodicals, Inc.

  20. Body condition of gilts at the end of gestation affects their mammary development. (United States)

    Farmer, C; Duarte, C R A; Vignola, M; Palin, M-F


    The impact of body condition at 110 d of gestation on mammary gland development, mammary gene expression, and hormonal and metabolite status of gilts was studied. Thirty-nine gilts were equally divided into 3 groups based on their backfat thickness at the end of gestation: 1) low backfat (LBF; 12-15 mm), 2) medium backfat (MBF; 17-19 mm), or 3) high backfat (HBF; 21-26 mm). Gilts had similar BW (138.1 ± 8.2 kg) and backfat thicknesses (16.4 ± 1.0 mm) at mating and the 3 groups were achieved via ingestion of varying amounts of feed throughout gestation. Jugular blood samples were obtained from all gilts at mating and at 109 d of gestation to assess hormonal and metabolic statuses, and animals were slaughtered on d 110 to collect mammary glands for compositional analyses and for measure of gene expression. The LBF gilts had less extraparenchymal tissue ( gilts. Mammary parenchyma from LBF gilts also tended to contain less DM ( gilts. None of the 15 genes studied in mammary parenchymal tissue differed in terms of expression level, and the rate of mammary cell proliferation was similar among treatments ( > 0.10). There was a tendency for circulating leptin concentrations on d 109 of gestation to be lower in LBF gilts than in MBF gilts ( gilts did not differ from those of the other treatments ( > 0.10). Current results demonstrate that being too thin at the end of gestation (12-15 mm backfat) has a negative impact on mammary development in gilts, whereas having backfats varying from 17 to 26 mm seems to have no detrimental effects on mammogenesis. Backfat thickness in late pregnancy must therefore be considered to achieve optimal sow lactation performance.

  1. Inhibition of peripubertal sheep mammary gland development by cysteamine through reducing progesterone and growth factor production. (United States)

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


    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.

  2. Loss of Panx1 Impairs Mammary Gland Development at Lactation: Implications for Breast Tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Michael K G Stewart

    Full Text Available Pannexin1 (Panx1 subunits oligomerize to form large-pore channels between the intracellular and extracellular milieu that have been shown to regulate proliferation, differentiation and cell death mechanisms. These key cellular responses are ultimately necessary for normal tissue development and function but the role of Panx1 in development, differentiation and function in many tissues remains unexplored, including that of the breast. Panx1 was identified to be expressed in the mammary gland through western blot and immunofluorescent analysis and is dynamically upregulated during pregnancy and lactation. In order to evaluate the role of Panx1 in the context of mammary gland development and function, Panx1-/- mice were evaluated in comparison to wild-type mice in the mammary glands of virgin, lactating and involuting mice. Our results revealed that Panx1 ablation did not affect virgin or involuting mammary glands following histological and whole mount analysis. Panx1 was necessary for timely alveolar development during early lactation based on a decreased number of alveolar lumen following histological analysis and reduced proliferation following Ki67 immunofluorescent labelling. Importantly, the loss of Panx1 in lactating mammary glands did not overtly affect epithelial or secretory differentiation of the mammary gland suggesting that Panx1 is not critical in normal mammary gland function. In addition, PANX1 mRNA expression was correlated with negative clinical outcomes in patients with breast cancer using in silico arrays. Together, our results suggest that Panx1 is necessary for timely alveolar development following the transition from pregnancy to lactation, which may have implications extending to patients with breast cancer.

  3. Conditional Wwox deletion in mouse mammary gland by means of two Cre recombinase approaches.

    Directory of Open Access Journals (Sweden)

    Brent W Ferguson

    Full Text Available Loss of WWOX expression has been reported in many different cancers including breast cancer. Elucidating the function of this gene in adult tissues has not been possible with full Wwox knockout models. Here we characterize the first conditional models of Wwox ablation in mouse mammary epithelium utilizing two transgenic lines expressing Cre recombinase, keratin 5-Cre (BK5-Cre and MMTV-Cre. In the BK5-Cre model we observed very efficient Wwox ablation in KO mammary glands. However, BK5-Cre Wwox KO animals die prematurely for unknown reasons. In the MMTV-Cre model we observed significant ablation of Wwox in mammary epithelium with no effect on survival. In both of these models we found that Wwox deletion resulted in impaired mammary branching morphogenesis. We demonstrate that loss of Wwox is not carcinogenic in our KO models. Furthermore, no evidence of increase proliferation or development of premalignant lesions was observed. In none of the models did loss of a single Wwox allele (i.e. haploinsufficiency have any observable phenotypic effect in mammary gland. To better understand the function of Wwox in the mammary gland, transcriptome profiling was performed. We observed that Wwox ablation results in the deregulation of genes involved in various cellular processes. We found that expression of the non-canonical Wnt ligand, Wnt5a, was significantly upregulated in Wwox KO mammary epithelium. Interestingly, we also determined that components of the Jak/Stat3 signaling pathway were upregulated in KO mice and this correlated with a very robust increase in phospho-Stat3 signaling, which warrants further testing. Even though the loss of Wwox expression in breast and other cancers is very well documented, our findings suggest that Wwox does not act as a classical tumor suppressor as previously thought.

  4. Nuclear repartitioning of galectin-1 by an extracellular glycan switch regulates mammary morphogenesis (United States)

    Bhat, Ramray; Belardi, Brian; Mori, Hidetoshi; Kuo, Peiwen; Tam, Andrew; Hines, William C.; Le, Quynh-Thu; Bertozzi, Carolyn R.; Bissell, Mina J.


    Branching morphogenesis in the mammary gland is achieved by the migration of epithelial cells through a microenvironment consisting of stromal cells and extracellular matrix (ECM). Here we show that galectin-1 (Gal-1), an endogenous lectin that recognizes glycans bearing N-acetyllactosamine (LacNAc) epitopes, induces branching migration of mammary epithelia in vivo, ex vivo, and in 3D organotypic cultures. Surprisingly, Gal-1’s effects on mammary patterning were independent of its glycan-binding ability and instead required localization within the nuclei of mammary epithelia. Nuclear translocation of Gal-1, in turn, was regulated by discrete cell-surface glycans restricted to the front of the mammary end buds. Specifically, α2,6–sialylation of terminal LacNAc residues in the end buds masked Gal-1 ligands, thereby liberating the protein for nuclear translocation. Within mammary epithelia, Gal-1 localized within nuclear Gemini bodies and drove epithelial invasiveness. Conversely, unsialylated LacNAc glycans, enriched in the epithelial ducts, sequestered Gal-1 in the extracellular environment, ultimately attenuating invasive potential. We also found that malignant breast cells possess higher levels of nuclear Gal-1 and α2,6–SA and lower levels of LacNAc than nonmalignant cells in culture and in vivo and that nuclear localization of Gal-1 promotes a transformed phenotype. Our findings suggest that differential glycosylation at the level of tissue microanatomy regulates the nuclear function of Gal-1 in the context of mammary gland morphogenesis and in cancer progression. PMID:27496330

  5. Mutant p53 Amplifies Epidermal Growth Factor Receptor Family Signaling to Promote Mammary Tumorigenesis. (United States)

    Yallowitz, Alisha R; Li, Dun; Lobko, Anthony; Mott, Daniel; Nemajerova, Alice; Marchenko, Natalia


    The EGFR family (ErbB2/Her2 and EGFR/ErbB1/Her1) often modulates the transcriptional program involved in promoting mammary tumorigenesis. In humans, the majority of ErbB2-positive sporadic breast cancers harbor p53 mutations, which correlate with poor prognosis. Also, the extremely high incidence of ErbB2-positive breast cancer in women with p53 germline mutations (Li-Fraumeni syndrome) suggests a key role of mutant p53 specifically in ErbB2-mediated mammary tumorigenesis. To examine the role of mutant p53 during ErbB2-mediated mammary tumorigenesis, a mutant p53 allele (R172H) was introduced into the (MMTV)-ErbB2/Neu mouse model system. Interestingly, we show in heterozygous p53 mice that mutant p53 R172H is a more potent activator of ErbB2-mediated mammary tumorigenesis than simple loss of p53. The more aggressive disease in mutant p53 animals was reflected by earlier tumor onset, increased mammary tumor multiplicity, and shorter survival. These in vivo and in vitro data provide mechanistic evidence that mutant p53 amplifies ErbB2 and EGFR signaling to promote the expansion of mammary stem cells and induce cell proliferation. This study identifies mutant p53 as an essential player in ErbB2 and EGFR-mediated mammary tumorigenesis and indicates the potential translational importance of targeting mutant p53 in this subset of patients with breast cancer. ©2015 American Association for Cancer Research.

  6. Histopathology of mammary gland in Staphylococcus aureus induced mastitis in mice

    Directory of Open Access Journals (Sweden)

    Jayaraj Fakkirappa Chinchali


    Full Text Available Objective: To investigate the histopathological changes of mouse mammary tissue damage in dose and durational pathogenicity of Staphylococcus aureus (S. aureus inoculums. Methods: The minimal tissue inflammation dose of S. aureus inoculum was determined by inoculating the lactating mice mammary gland to observe the mortality rate at 24, 48, 72 and 96 h of infection for each inoculum dilutions. To study dose pathogenicity, lactating mice were divided into one control and four induced groups of 5 mice each. S. aureus inoculums doses of 0.8伊101, 1.4 伊102, 2伊102 and 2.8伊103 colony forming unit were inoculated to the induced groups II, III, IV and V respectively. Mice were sacrificed and mammary gland tissues were harvested after 48 h of infection. Similarly to study of durational pathogenicity, a dose of 2伊102 colony forming unit of S. aureus inoculums was inoculated to the induced groups II, III, IV and V respectively. Mice were sacrificed and mammary gland tissues were harvested after 24, 48, 72 and 96 h of infection. Body and mammary gland were weighed and histopathological responses of the tissue damage were observed for both dose and durational pathogenicity ’s of S. aureus inoculums. Results: The observations indicated mastitis symptoms, decrease in body and mammary gland weights. Histopathological evidences revealed massive infiltration of polymorphonuclear neutrophil leukocytes, damage of alveoli and secretory products as the doses and durations of S. aureus inoculum increased compared to the control. Conclusions: The present study revealed that damage in mammary gland tissue of mice increased as the dose and duration of S. aureus inoculums increased.

  7. Accelerators in Science and Technology

    CERN Document Server

    Kailas, S


    Accelerators built for basic research in frontier areas of science have become important and inevitable tools in many areas of science and technology. Accelerators are examples of science driven high technology development. Accelerators are used for a wide ranging applications, besides basic research. Accelerator based multidisciplinary research holds great promise

  8. Plasma-based accelerator structures

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, Carl B. [Univ. of California, Berkeley, CA (United States)


    Plasma-based accelerators have the ability to sustain extremely large accelerating gradients, with possible high-energy physics applications. This dissertation further develops the theory of plasma-based accelerators by addressing three topics: the performance of a hollow plasma channel as an accelerating structure, the generation of ultrashort electron bunches, and the propagation of laser pulses is underdense plasmas.

  9. Paternal selenium deficiency but not supplementation during preconception alters mammary gland development and 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis in female rat offspring. (United States)

    Guido, Luiza N; Fontelles, Camile C; Rosim, Mariana P; Pires, Vanessa C; Cozzolino, Silvia M F; Castro, Inar A; Bolaños-Jiménez, Francisco; Barbisan, Luis F; Ong, Thomas P


    Breast cancer is a global public health problem and accumulating evidence indicates early-life exposures as relevant factors in the disease risk determination. Recent studies have shown that paternal nutrition can influence offspring health including breast cancer risk. Selenium is a micronutrient with essential role in central aspects of embryogenesis, male fertility and cancer and that has been extensively studied as a chemopreventive agent in several breast cancer experimental models. Thus, we designed an animal study to evaluate whether paternal selenium deficiency or supplementation during preconception could affect the female offspring mammary gland development and breast cancer susceptibility. Male Sprague-Dawley rats were fed AIN93-G diet containing 0.15 ppm (control diet), 0.05 ppm (deficient diet) or 1 ppm (supplemented diet) of selenium for 9 weeks and mated with control female rats. Mammary carcinogenesis was induced with 7,12-dimethylbenz[a]anthracene (DMBA) in their female offspring. Paternal selenium deficiency increased the number of terminal end buds, epithelial elongation and cell proliferation in the mammary gland of the female rat offspring and these effects were associated with higher susceptibility to DMBA-induced mammary tumors (increased incidence and higher grade tumors). On the other hand, paternal selenium supplementation did not influence any of these parameters. These results highlight the importance of father's nutrition including selenium status as a relevant factor affecting daughter's breast cancer risk and paternal preconception as a potential developmental stage to start disease preventive strategies. © 2016 UICC.

  10. Particle accelerator physics

    CERN Document Server

    Wiedemann, Helmut


    Particle Accelerator Physics is an in-depth and comprehensive introduction to the field of high-energy particle acceleration and beam dynamics. Part I gathers the basic tools, recalling the essentials of electrostatics and electrodynamics as well as of particle dynamics in electromagnetic fields. Part II is an extensive primer in beam dynamics, followed in Part III by the introduction and description of the main beam parameters. Part IV is devoted to the treatment of perturbations in beam dynamics. Part V discusses the details of charged particle accleration. Part VI and Part VII introduce the more advanced topics of coupled beam dynamics and the description of very intense beams. Part VIII is an exhaustive treatment of radiation from accelerated charges and introduces important sources of coherent radiation such as synchrotrons and free-electron lasers. Part IX collects the appendices gathering useful mathematical and physical formulae, parameters and units. Solutions to many end-of-chapter problems are give...

  11. Quasar Jet Acceleration (United States)

    Polito, Nicholas; Hough, David


    We observed radio jets in six lobe-dominated quasars (LDQs) from 1995 to 2008 using the NRAO VLBA at 8.4 and 15 GHz. These observations have tracked jet component positions and velocities over that time period. There is a correlation between apparent jet speed and projected core distance in these LDQs at greater than 99 per cent confidence levels (Hough 2008, Extragalactic Jets, eds: Rector and DeYoung, ASP, p. 274). Four of our sources show this effect particularly strongly. We only tracked single jet components over relatively short distances, but the assumption of a unique velocity profile allows us to study component motion on an effective timescale of approximately 20-50 years. Results for 3C207 and 3C263 show a good fit using a constant acceleration model. The cause of such acceleration is still unknown, though ``magnetic acceleration'' by a gradient in magnetic field pressure is one possibility.

  12. Superconducting Accelerator Magnets

    CERN Document Server

    Mess, K H; Wolff, S


    The main topic of the book are the superconducting dipole and quadrupole magnets needed in high-energy accelerators and storage rings for protons, antiprotons or heavy ions. The basic principles of low-temperature superconductivity are outlined with special emphasis on the effects which are relevant for accelerator magnets. Properties and fabrication methods of practical superconductors are described. Analytical methods for field calculation and multipole expansion are presented for coils without and with iron yoke. The effect of yoke saturation and geometric distortions on field quality is studied. Persistent magnetization currents in the superconductor and eddy currents the copper part of the cable are analyzed in detail and their influence on field quality and magnet performance is investigated. Superconductor stability, quench origins and propagation and magnet protection are addressed. Some important concepts of accelerator physics are introduced which are needed to appreciate the demanding requirements ...

  13. Accelerating the culture change! (United States)

    Klunk, S W; Panetta, J; Wooten, J


    Exide Electronics, a major supplier of uninterruptible power system equipment, embarked on a journey of changing a culture to improve quality, enhance customer responsiveness, and reduce costs. This case study examines the evolution of change over a period of seven years, with particular emphasis on the most recent years, 1992 through 1995. The article focuses on the Raleigh plant operations and describes how each succeeding year built on the successes and fixed the shortcomings of the prior years to accelerate the culture change, including corrective action and continuous improvement processes, organizational structures, expectations, goals, achievements, and pitfalls. The real challenge to changing the culture was structuring a dynamic approach to accelerate change! The presentation also examines how the evolutionary process itself can be created and accelerated through ongoing communication, regular feedback of progress and goals, constant evaluation and direction of the process, and measuring and paying for performance.

  14. Artificial seismic acceleration (United States)

    Felzer, Karen R.; Page, Morgan T.; Michael, Andrew J.


    In their 2013 paper, Bouchon, Durand, Marsan, Karabulut, 3 and Schmittbuhl (BDMKS) claim to see significant accelerating seismicity before M 6.5 interplate mainshocks, but not before intraplate mainshocks, reflecting a preparatory process before large events. We concur with the finding of BDMKS that their interplate dataset has significantly more fore- shocks than their intraplate dataset; however, we disagree that the foreshocks are predictive of large events in particular. Acceleration in stacked foreshock sequences has been seen before and has been explained by the cascade model, in which earthquakes occasionally trigger aftershocks larger than themselves4. In this model, the time lags between the smaller mainshocks and larger aftershocks follow the inverse power law common to all aftershock sequences, creating an apparent acceleration when stacked (see Supplementary Information).

  15. Microelectromechanical acceleration-sensing apparatus

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Robb M. (Albuquerque, NM); Shul, Randy J. (Albuquerque, NM); Polosky, Marc A. (Albuquerque, NM); Hoke, Darren A. (Albuquerque, NM); Vernon, George E. (Rio Rancho, NM)


    An acceleration-sensing apparatus is disclosed which includes a moveable shuttle (i.e. a suspended mass) and a latch for capturing and holding the shuttle when an acceleration event is sensed above a predetermined threshold level. The acceleration-sensing apparatus provides a switch closure upon sensing the acceleration event and remains latched in place thereafter. Examples of the acceleration-sensing apparatus are provided which are responsive to an acceleration component in a single direction (i.e. a single-sided device) or to two oppositely-directed acceleration components (i.e. a dual-sided device). A two-stage acceleration-sensing apparatus is also disclosed which can sense two acceleration events separated in time. The acceleration-sensing apparatus of the present invention has applications, for example, in an automotive airbag deployment system.

  16. Monoenergetic laser wakefield acceleration

    Directory of Open Access Journals (Sweden)

    N. E. Andreev


    Full Text Available Three dimensional test particle simulations are applied to optimization of the plasma-channeled laser wakefield accelerator (LWFA operating in a weakly nonlinear regime. Electron beam energy spread, emittance, and luminosity depend upon the proportion of the electron bunch size to the plasma wavelength. This proportion tends to improve with the laser wavelength increase. We simulate a prospective two-stage ∼1GeV LWFA with controlled energy spread and emittance. The input parameters correspond to realistic capabilities of the BNL Accelerator Test Facility that features a picosecond-terawatt CO_{2} laser and a high-brightness electron gun.

  17. Shielding high energy accelerators

    CERN Document Server

    Stevenson, Graham Roger


    After introducing the subject of shielding high energy accelerators, point source, line-of-sight models, and in particular the Moyer model. are discussed. Their use in the shielding of proton and electron accelerators is demonstrated and their limitations noted. especially in relation to shielding in the forward direction provided by large, flat walls. The limitations of reducing problems to those using it cylindrical geometry description are stressed. Finally the use of different estimators for predicting dose is discussed. It is suggested that dose calculated from track-length estimators will generally give the most satisfactory estimate. (9 refs).

  18. Accelerating News Issue 4

    CERN Document Server

    Szeberenyi, A; Wildner, E


    In this winter issue, we are very pleased to announce the approval of EuCARD-2 by the European Commission. We look at the conclusions of EUROnu in proposing future neutrino facilities at CERN, a new milestone reached by CLIC and progress on the SPARC upgrade using C-band technology. We also report on recent events: second Joint HiLumi LHC-LARP Annual Meeting and workshop on Superconducting technologies for the Next Generation of Accelerators aiming at closer collaboration with industry. The launch of the Accelerators for Society brochure is also highlighted.

  19. Evaluation of serum haptoglobin and C-reactive protein in dogs with mammary tumors. (United States)

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


    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 (Pdogs 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.

  20. Lymphoscintigraphic visualization of internal mammary nodes with subtumoral injection of radiocolloid in patients with breast cancer. (United States)

    Shimazu, Kenzo; Tamaki, Yasuhiro; Taguchi, Tetsuya; Motomura, Kazuyoshi; Inaji, Hideo; Koyama, Hiroki; Kasugai, Tsutomu; Wada, Akira; Noguchi, Shinzaburo


    To determine whether subtumoral injection of radiocolloid is useful for lymphoscintigraphic visualization of the internal mammary node and in sentinel lymph node (SLN) biopsy of the axilla in breast cancer patients. The presence of retromammary lymphatics connecting to the axillary and internal mammary basins has been demonstrated by early anatomic studies. Thus, it is hypothesized that some lymph, especially that from the parenchyma under the tumor, may drain into both the axillary and internal mammary basins. Patients (n = 196) with T1-2, N0 breast cancer underwent preoperative lymphoscintigraphy with radiocolloid (technetium 99m tin colloid) injection into various sites of the breast, followed by SLN biopsy using the combined method with blue dye. Patients were divided into four groups: group A (n = 41), peritumoral injection of both radiocolloid and blue dye; group B (n = 70), periareolar radiocolloid and peritumoral blue dye; group C (n = 45), intradermal radiocolloid and periareolar blue dye; and group D (n = 40), subtumoral radiocolloid and intradermal blue dye. A retrospective analysis of 1,297 breast cancer patients who underwent extended radical mastectomy with internal mammary node dissection was also conducted to determine the relationship between vertical tumor location (superficial or deep) and frequency of axillary and internal mammary node metastases. One patient (2%) in group A, 3 (4%) in group B, 0 (0%) in group C, and 15 (38%) in group D exhibited hot spots in the internal mammary region on lymphoscintigraphy (P basin was significantly lower in group D than in the other groups. In contrast, the mismatch rate (some SLNs were identified by radiocolloid and other SLNs were identified by blue dye, but no SLN was identified by both in the same patient) was significantly higher in group D than in the other groups. In patients treated with extended radical mastectomy, positivity of axillary and internal mammary metastases was significantly higher in

  1. Feline mammary adenocarcinoma: tumor size as a prognostic indicator. (United States)

    Viste, Jodi R; Myers, Sherry L; Singh, Baljit; Simko, Elemir


    Mammary carcinomas and adenocarcinomas (MACs) are relatively common tumors in cats. The postexcisional survival period of affected cats is inversely proportional to tumor size, but the reported median survival periods for different tumor size categories is quite variable. This variability diminishes the prognostic value of reported data. In our study, cats with MACs greater than 3 cm in diameter had a 12-month median survival period, whereas those with MACs less than 3 cm in diameter had a 21-month survival period. Survival periods for cats with MACs smaller than 3 cm ranged from 3 to 54 months; therefore, tumor size alone is of limited prognostic value in cats with MACs smaller than 3 cm in diameter. In cats with MACs larger than 3 cm in diameter, tumor size appears to have much higher prognostic relevance, because this study, as well as others, have indicated that cats with MACs greater than 3 cm in diameter have a poor prognosis, with median survival periods ranging from 4 to 12 months.

  2. Influence of mast cells on two murine mammary adenocarcinomas. (United States)

    de Cidre, L L; Eijan, A M; Bertolesi, G; Isturiz, M; Sacerdote de Lustig, E


    A high content of mast cells (MC) is considered characteristic of neoplasias. Some researchers postulate MC as enhancers of tumor development, others as inhibitors. The purpose of this study was to evaluate the ability of peritoneal cavity MC to modulate the in vivo and in vitro growth of two murine mammary adenocarcinomas with low (M3) and high (MM3) metastatic capacity. MC from the peritoneal cavity of normal (NMC) or tumor-bearing mice (TMC) were used. TMC, which by histochemical methods appeared degranulated, were not able to modify the tumorigenicity of both tumors. NMC, in contrast, decreased M3 tumor incidence and cell proliferation in vitro and increased the latency period of only MM3 tumors. No changes in the number of spontaneous lung metastases could be seen in experiments carried out either with NMC or TMC. We conclude that NMC, which are rich in chemical mediators, can modulate some of the first steps of tumor development. Once tumor-mediated degranulation occurs, MC become unable to regulate it.

  3. Culture models of human mammary epithelial cell transformation

    Energy Technology Data Exchange (ETDEWEB)

    Stampfer, Martha R.; Yaswen, Paul


    Human pre-malignant breast diseases, particularly ductal carcinoma in situ (DCIS)3 already display several of the aberrant phenotypes found in primary breast cancers, including chromosomal abnormalities, telomerase activity, inactivation of the p53 gene and overexpression of some oncogenes. Efforts to model early breast carcinogenesis in human cell cultures have largely involved studies in vitro transformation of normal finite lifespan human mammary epithelial cells (HMEC) to immortality and malignancy. We present a model of HMEC immortal transformation consistent with the know in vivo data. This model includes a recently described, presumably epigenetic process, termed conversion, which occurs in cells that have overcome stringent replicative senescence and are thus able to maintain proliferation with critically short telomeres. The conversion process involves reactivation of telomerase activity, and acquisition of good uniform growth in the absence and presence of TFGB. We propose th at overcoming the proliferative constraints set by senescence, and undergoing conversion, represent key rate-limiting steps in human breast carcinogenesis, and occur during early stage breast cancer progression.

  4. Study of aggressiveness prediction of mammary adenocarcinoma by Raman spectroscopy (United States)

    Andrade Bitar, Renata; da Silva Martinho, Herculano; Zambelli Ramalho, Leandra Náira; dos Santos Junior, Arnaldo Rodrigues; Silva Ramalho, Fernando; Raniero, Leandro; Martin, Airton A.


    Although there are many articles focused on in vivo or ex vivo Raman analysis for cancer diagnosis, to the best of our knowledge its potential to predict the aggressiveness of tumor has not been fully explored yet. In this work Raman spectra in the finger print region of ex vivo breast tissues of both healthy mice (normal) and mice with induced mammary gland tumors (abnormal) were measured and associated to matrix metalloproteinase-19 (MMP-19) immunohistochemical exam. It was possible to verify that normal breast, benign lesions, and adenocarcinomas spectra, including the subtypes (cribriform, papillary and solid) could have their aggressiveness diagnosed by vibrational Raman bands. By using MMP- 19 exam it was possible to classify the samples by malignant graduation in accordance to the classification results of Principal Component Analysis (PCA). The spectra NM /MH were classified correctly in 100% of cases; CA/CPA group had 60 % of spectra correctly classified and for PA/AS 54% of the spectra were correctly classified.

  5. Clinicopathological characterization of mammary analogue secretory carcinoma of salivary glands. (United States)

    Chiosea, Simion I; Griffith, Christopher; Assaad, Adel; Seethala, Raja R


    Mammary analogue secretory carcinoma (MASC) is a recently described tumour with ETV6 translocation. We aimed to characterize the clinical significance of recognizing MASC. Thirty-six patients with MASC (27 identified retrospectively and nine prospectively) are presented. Historically, MASC mimicked other salivary tumours, as follows: 14 of 37 (37.8%) adenocarcinoma, not otherwise specified, 11 of 89 (12.4%) acinic cell carcinomas (AciCC), one of five (20%) mucin-producing signet ring adenocarcinomas, and one of 165 (0.6%) mucoepidermoid carcinomas. Demographically, MASC affected males more commonly (1.4:1). The average age at diagnosis was 45.7 years. Parotid gland was the most common site of involvement (26 of 36, 72.2%), although other head and neck sites, including the base of tongue, were affected. Of 18 patients with neck dissection, lymph node involvement was identified in four patients (four of 18, 22.2%). Survival analysis of MASC cases presented here, combined with those reported previously, revealed a mean disease-free survival for patients with MASC of 92 months [n = 29; 95% confidence interval (CI) 71-115 months], compared with a mean DFS of 121 months for patients with AciCC (n = 38; 95% CI 92-149, P = 0.43). Although perhaps slightly more aggressive, MASC clinical outcome mimics that of AciCC. © 2012 Blackwell Publishing Ltd.

  6. Three-dimensional Mammary Epithelial Cell Morphogenesis Model for Analysis of TGFß Signaling. (United States)

    Rashidian, Juliet; Luo, Kunxin


    Culturing mammary epithelial cells in laminin-rich extracellular matrices (three dimensional or 3D culture) offers significant advantages over that in the conventional two-dimensional (2D) tissue culture system in that it takes into considetation the impact of extracellular matrix (ECM) microenvironment on the proliferation, survival, and differentiation of mammary epithelial cells. When grown in the 3D culture, untransformed mammary epithelial cells undergo morphogenesis to form a multicellular and polarized acini-like structure that functionally mimics the differentiated alveoli in the pregnancy mammary gland. This process is subjected to regulation by many growth factors and cytokines. The transforming growth factor-ß (TGFß) is a multipotent cytokine that regulates multiple aspects of development and tumorigenesis. In addition to its effects on epithelial cell proliferation, survival, and differentiation, it is also a potent regulator of the cell-matrix interaction. Thus, the 3D culture model may recapitulate the complex in vivo epithelial cell microenvironment and allow us to fully evaluate the role of TGFß signaling in multiple aspects of normal and cancerous cell behavior. In this chapter we provide detailed protocols for growing mammary epithelial cells in the 3D Matrigel for analysis of signaling pathways.

  7. Cdk2-Null Mice Are Resistant to ErbB-2-Induced Mammary Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Dipankar Ray


    Full Text Available The concept of targeting G1 cyclin-dependent kinases (CDKs in breast cancer treatments is supported by the fact that the genetic ablation of Cdk4 had minimal impacts on normal cell proliferation in majority of cell types, resulting in near-normal mouse development, whereas such loss of Cdk4 completely abrogated ErbB-2/neu-induced mammary tumorigenesis in mice. In most human breast cancer tissues, another G1-regulatory CDK, CDK2, is also hyperactivated by various mechanisms and is believed to be an important therapeutic target. In this report, we provide genetic evidence that CDK2 is essential for proliferation and oncogenesis of murine mammary epithelial cells. We observed that 87% of Cdk2-null mice were protected from ErbB-2-induced mammary tumorigenesis. Mouse embryonic fibroblasts isolated from Cdk2-null mouse showed resistance to various oncogene-induced transformation. Previously, we have reported that hemizygous loss of Cdc25A, the major activator of CDK2, can also protect mice from ErbB-2-induced mammary tumorigenesis [Cancer Res (2007 67(14: 6605–11]. Thus, we propose that CDC25A-CDK2 pathway is critical for the oncogenic action of ErbB-2 in mammary epithelial cells, in a manner similar to Cyclin D1/CDK4 pathway.

  8. Expression of NOS and VEGF in feline mammary tumours and their correlation with angiogenesis. (United States)

    Islam, M S; Matsumoto, M; Hidaka, R; Miyoshi, N; Yasuda, N


    In order to define the role of nitric oxide (NO) in feline mammary tumours, the expression of endothelial or inducible nitric oxide synthase (e/iNOS) and vascular endothelial growth factor (VEGF), and their relationship with angiogenesis, was investigated in 23 feline mammary tumours (two hyperplastic, 19 adenocarcinoma, one osteosarcoma and one squamous cell carcinoma) by immunohistochemistry. Tumour angiogenesis was assessed by CD31 immunostaining and was expressed as microvessel density (MVD). In general, iNOS immunoreactivity was localised in tumour cells and occasionally in stromal myofibroblasts, whereas eNOS and VEGF were localised in the cytoplasm of tumour epithelial cells and endothelium. In malignancy, expression of iNOS increased from well- to less-differentiated phenotypes (Grades 1-3) and was significantly higher in G3 and G2 when compared with G1 cases. However, increasing eNOS expression was limited only in hyperplastic lesions and showed no significant changes among the grades. In addition, expression of iNOS was positively correlated with VEGF and MVD in feline mammary tumours and both measures were significantly greater in less differentiated phenotypes (Pfeline mammary tumours depended on tumour grade, and the positive correlations between iNOS and angiogenic markers suggests that iNOS synthesised by tumour cells promotes tumour growth. Thus, iNOS can be used as an important immunohistochemical marker to determine the degree of malignancy and prognosis of feline mammary carcinoma. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model. (United States)

    Zheng, Ming-Jie; Wang, Jue; Xu, Lu; Zha, Xiao-Ming; Zhao, Yi; Ling, Li-Jun; Wang, Shui


    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.

  10. Immunohistochemical expression of E-cadherin and β-catenin in feline mammary tumours. (United States)

    Zappulli, V; De Cecco, S; Trez, D; Caliari, D; Aresu, L; Castagnaro, M


    E-cadherin and β-catenin have been studied in carcinogenesis and tumour progression and reduced membrane expression of these molecules in canine mammary tumours has been associated with a poor prognosis. The present study investigated immunohistochemically the expression of E-cadherin and β-catenin in 53 mammary tumours and 48 hyperplastic or dysplastic lesions from 57 queens. E-cadherin and β-catenin expression was membranous in all samples and there was a significant decrease in expression in malignant tumours and metastases. Cytoplasmic expression of both markers was inversely correlated to the membrane localization. β-catenin nuclear labelling was detected in one lymph node metastasis (60% positive cells) and in the basal/myoepithelial cells of 6/7 ductal tumours. No correlation with survival was found for either marker. These results confirm the role of these proteins in maintaining tissue architecture and in inhibiting cell invasiveness and potentially indicate the oncogenic potential of the Wnt/β-catenin transduction pathway in feline mammary tumours. In addition, specific independent expression of β-catenin in the nuclei of basal/myoepithelial cells might suggest that this molecule is involved in regulation of the mammary stem/pluripotent cell component. Further studies should include more cases of benign mammary neoplasia and further investigate β-catenin nuclear expression in ductal tumours. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Functional adaptations of the transcriptome to mastitis-causing pathogens: the mammary gland and beyond. (United States)

    Loor, Juan J; Moyes, Kasey M; Bionaz, Massimo


    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.

  12. Salinomycin inhibits canine mammary carcinoma in vitro by targeting cancer stem cells. (United States)

    Du, Hongchao; Zhou, Bin; Zhang, Hong; Jin, Yipeng; Zhang, Di; Lin, Degui


    Salinomycin (SAL), a polyether ionophore antibiotic, has been demonstrated to selectively kill cancer stem cells (CSCs) in various types of human tumor. The aim of the present study was to investigate the effects of SAL on canine mammary CSCs. CSCs in canine mammary carcinoma cell lines (CMT7364 and CIPp) were identified using a sphere formation assay and flow cytometry. The chemoresistance, invasive potential and expression of stem cell-associated proteins of these spheres was then analyzed. This demonstrated that the spheres exhibited characteristics of CSCs, including a cluster of differentiation (CD)44+/CD24-/low phenotype, upregulation of Wnt/β-catenin signaling pathway-associated proteins and chemoresistance. The viability of the spheres was decreased in a concentration- and time-dependent manner following treatment with SAL, and the spheres did not exhibit increased resistance to SAL compared with their parental cells. In addition, exposure to SAL inhibited sphere-formation and invasive potential in canine mammary CSCs in a dose-dependent manner. Furthermore, SAL decreased the CD44+/CD24-/low population and downregulated the expression of Wnt/β-catenin signaling-associated proteins (β-catenin, Cyclin D1 and octamer-binding transcription factor 4) in the spheres. In conclusion, the present study demonstrated that SAL is an effective inhibitor of canine mammary CSCs in vitro, indicating that SAL is a promising chemotherapeutic agent for the treatment of canine mammary carcinoma.

  13. Effects of glucose on lactose synthesis in mammary epithelial cells from dairy cow. (United States)

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


    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.

  14. Numb and Numbl act to determine mammary myoepithelial cell fate, maintain epithelial identity, and support lactogenesis. (United States)

    Zhang, Yue; Li, Fengyin; Song, Yongli; Sheng, Xiaole; Ren, Fazheng; Xiong, Kai; Chen, Lei; Zhang, Hongquan; Liu, Dequan; Lengner, Christopher J; Xue, Lixiang; Yu, Zhengquan


    Mammary epithelium is comprised of an inner layer of luminal epithelial cells and an outer layer of contractile myoepithelial cells with mesenchymal properties. These two compartments interact throughout mammary morphogenesis to form branching ducts during puberty and terminate in secretory alveoli during lactation. It is not known how the myoepithelial cell lineage is specified, nor how signals in myoepithelial cells contribute to lactogenesis. Here, we show that Numb and Numbl are enriched in mammary myoepithelial cells, with their expression peaking during pregnancy. We use conditional Numb- and Numbl-knockout mouse models to demonstrate that loss of Numb/Numbl compromised the myoepithelial layer and expanded the luminal layer, led epithelial cells to undergo epithelial-to-mesenchymal transition, and resulted in lactation failure as a result of abnormal alveolar formation during pregnancy. Numb and Numbl function via repression of the Notch signaling pathway and of the p53-p21 axis during mammary gland development. These findings highlight the importance of Numb and Numbl in the control of myoepithelial cell fate determination, epithelial identity, and lactogenesis.-Zhang Y., Li, F., Song, Y., Sheng, X., Ren, F., Xiong, K., Chen, L., Zhang, H., Liu, D., Lengner, C. J., Xue, L., Yu, Z. Numb and Numbl act to determine mammary myoepithelial cell fate, maintain epithelial identity, and support lactogenesis. © FASEB.

  15. Concentration of citrate in the mammary secretion of sows during lactogenesis II and established lactation. (United States)

    Holmes, M A; Hartmann, P E


    The functional significance of citrate in the mammary secretion of six sows was investigated during the second stage of lactogenesis (lactogenesis II) and established lactation. The changes in the concentrations of progesterone and lactose in the maternal blood, and lactose, Na and K in the mammary secretion, suggested that lactogenesis II began during the final day of pregnancy. The concentration of citrate in the mammary secretion of the sows during lactogenesis II was high and varied from 5.4 (SEM 0.5) mM at day 0.5 post partum to 6.8 (SEM 0.4) mM at day 1.5 post partum. There was a decline of approximately 30% in the concentration of citrate in the milk of sows during the first week of lactation. These findings suggest that, in contrast to all other species studied previously, milk citrate is not a harbinger of lactogenesis II in the sow. However, the changes in the concentration of citrate in the mammary secretions of sows may reflect changes in the rate of de novo synthesis of fatty acids that take place in the mammary glands of sows during lactogenesis II and established lactation.

  16. Genes regulating lipid and protein metabolism are highly expressed in mammary gland of lactating dairy goats. (United States)

    Shi, Hengbo; Zhu, Jiangjiang; Luo, Jun; Cao, Wenting; Shi, Huaiping; Yao, Dawei; Li, Jun; Sun, Yuting; Xu, Huifen; Yu, Kang; Loor, Juan J


    Dairy goats serve as an important source of milk and also fulfill agricultural and economic roles in developing countries. Understanding the genetic background of goat mammary gland is important for research on the regulatory mechanisms controlling tissue function and the synthesis of milk components. We collected tissue at four different stages of goat mammary gland development and generated approximately 25 GB of data from Illumina de novo RNA sequencing. The combined reads were assembled into 51,361 unigenes, and approximately 60.07 % of the unigenes had homology to other proteins in the NCBI non-redundant protein database (NR). Functional classification through eukaryotic Ortholog Groups of Protein (KOG), gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that the unigenes from goat mammary glands are involved in a wide range of biological processes and metabolic pathways, including lipid metabolism and lactose metabolism. The results of qPCR revealed that genes encoding FABP3, FASN, SCD, PLIN2, whey proteins (LALBA and BLG), and caseins (CSN1S1, CSN1S2, CSN2 and CSN3) at 100 and 310 days postpartum increased significantly compared with the non-lactating period. In addition to their role in lipid and protein synthesis, the higher expression at 310 days postpartum could contribute to mammary cell turnover during pregnancy. In conclusion, this is the first study to characterize the complete transcriptome of goat mammary glands and constitutes a comprehensive genomic resource available for further studies of ruminant lactation.

  17. Lineage-Biased Stem Cells Maintain Estrogen-Receptor-Positive and -Negative Mouse Mammary Luminal Lineages

    Directory of Open Access Journals (Sweden)

    Chunhui Wang


    Full Text Available Delineating the mammary differentiation hierarchy is important for the study of mammary gland development and tumorigenesis. Mammary luminal cells are considered a major origin of human breast cancers. However, how estrogen-receptor-positive (ER+ and ER− luminal cells are developed and maintained remains poorly understood. The prevailing model suggests that a common stem/progenitor cell generates both cell types. Through genetic lineage tracing in mice, we find that SOX9-expressing cells specifically contribute to the development and maintenance of ER− luminal cells and, to a lesser degree, basal cells. In parallel, PROM1-expressing cells give rise only to ER+ luminal cells. Both SOX9+ and PROM1+ cells specifically sustain their respective lineages even after pregnancy-caused tissue remodeling or serial transplantation, demonstrating characteristic properties of long-term repopulating stem cells. Thus, our data reveal that mouse mammary ER+ and ER− luminal cells are two independent lineages that are maintained by distinct stem cells, providing a revised mammary epithelial cell hierarchy.

  18. Na(+) /H(+) exchanger 1 (NHE1) function is necessary for maintaining mammary tissue architecture. (United States)

    Jenkins, Edmund C; Debnath, Shawon; Varriano, Sophia; Gundry, Stephen; Fata, Jimmie E


    The mammary gland is an ideal model to study the link between form and function in normal tissue. Perhaps as interesting as the cues necessary to generate this structure are the signals required to maintain its branched architecture over the lifetime of the organism, since likely these pathways are de-regulated in malignancies. Previously, we have shown that the Na(+) /H(+) exchanger 1 (NHE1), a critical regulator of intracellular pH, was necessary for mammary branching morphogenesis. Here we provide strong evidence that NHE1 function is also necessary for maintaining mammary branched architecture. Inhibition of NHE1 with 5-N-Methy-N-isobutyl amiloride (MIA) on branched structures resulted in a rapid (within 24 hr) and reversible loss of branched architecture that was not accompanied by any overt changes in cell proliferation or cell death. NHE1 inhibition led to a significant acidification of intracellular pH in the branched end buds that preceded a number of events, including altered tissue polarity of myoepithelial cells, loss of NHE1 basal polarity, F-actin rearrangements, and decreased E-cadherin expression. Our results implicate NHE1 function and intracellular pH homeostasis as key factors that maintain mammary tissue architecture, thus, indirectly allowing for mammary function as a milk-providing (form) and -producing (function) gland. Copyright © 2013 Wiley Periodicals, Inc.

  19. Survey radiography and computerized tomography imaging of the thorax in female dogs with mammary tumors

    Directory of Open Access Journals (Sweden)

    Giordano Tatiana


    Full Text Available Abstract Background Accurate early diagnosis of lung metastases is important for establishing therapeutic measures. Therefore, the present study aimed to compare survey thoracic radiographs and computerized tomography (CT scans to specifically identify lung metastases in female dogs with mammary tumors. Methods Twenty-one female dogs, weighing 3 to 34 kg and aged from 5 years to 14 years and 10 months, with mammary tumors were studied. In all dogs before the imaging examinations, fine-needle aspiration cytology of the mammary tumors was performed to confirm the diagnosis. Three-view thoracic radiographs were accomplished: right lateral, left lateral and ventrodorsal views. Sequential transverse images of the thorax were acquired on a spiral Scanner, before and after intravenous bolus injection of nonionic iodine contrast. Soft-tissue and lung windows were applied. All the mammary tumors were surgically removed and examined histologically. Results The correlation between the cytological and histological results regarding presence of malignancy was observed in only 17 cases. In radiographic examinations, no dog displayed signs of lung metastases or thorax chest lesions. CT detected lung metastasis in two cases, while small areas of lung atelectasis located peripherally were found in 28.57% of the dogs. Conclusion In this study population, spiral CT showed higher sensitivity than chest radiographies to detect lung metastasis; this indicates that CT should be performed on all female dogs with malignant mammary tumors.

  20. Global changes in the mammary epigenome are induced by hormonal cues and coordinated by Ezh2. (United States)

    Pal, Bhupinder; Bouras, Toula; Shi, Wei; Vaillant, François; Sheridan, Julie M; Fu, Naiyang; Breslin, Kelsey; Jiang, Kun; Ritchie, Matthew E; Young, Matthew; Lindeman, Geoffrey J; Smyth, Gordon K; Visvader, Jane E


    The mammary epithelium is a dynamic, highly hormone-responsive tissue. To explore chromatin modifications underlying its lineage specification and hormone responsiveness, we determined genome-wide histone methylation profiles of mammary epithelial subpopulations in different states. The marked differences in H3K27 trimethylation between subpopulations in the adult gland suggest that epithelial cell-fate decisions are orchestrated by polycomb-complex-mediated repression. Remarkably, the mammary epigenome underwent highly specific changes in different hormonal contexts, with a profound change being observed in the global H3K27me3 map of luminal cells during pregnancy. We therefore examined the role of the key H3K27 methyltransferase Ezh2 in mammary physiology. Its expression and phosphorylation coincided with H3K27me3 modifications and peaked during pregnancy, driven in part by progesterone. Targeted deletion of Ezh2 impaired alveologenesis during pregnancy, preventing lactation, and drastically reduced stem/progenitor cell numbers. Taken together, these findings reveal that Ezh2 couples hormonal stimuli to epigenetic changes that underpin progenitor activity, lineage specificity, and alveolar expansion in the mammary gland. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.