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Sample records for 4t1 murine breast

  1. Human Mesenchymal Stromal Cells Transplantation May Enhance or Inhibit 4T1 Murine Breast Adenocarcinoma through Different Approaches

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    T. Jazedje

    2015-01-01

    Full Text Available The use of Mesenchymal Stromal Cells (MSCs aiming to treat cancer has shown very contradictory results. In an attempt to clarify the contradictory results reported in the literature and the possible role of human fallopian tube Mesenchymal Stromal Cells (htMSCs against breast cancer, the aim of this study was to evaluate the clinical effect of htMSCs in murine mammary adenocarcinoma using two different approaches: (1 coinjections of htMSCs and 4T1 murine tumor cell lineage and (2 injections of htMSCs in mice at the initial stage of mammary adenocarcinoma development. Coinjected animals had a more severe course of the disease and a reduced survival, while tumor-bearing animals treated with 2 intraperitoneal injections of 106 htMSCs showed significantly reduced tumor growth and increased lifespan as compared with control animals. Coculture of htMSCs and 4T1 tumor cells revealed an increase in IL-8 and MCP-1 and decreased VEGF production. For the first time, we show that MSCs isolated from a single source and donor when injected in the same animal model and tumor can lead to opposite results depending on the experimental protocol. Also, our results demonstrated that htMSCs can have an inhibitory effect on the development of murine mammary adenocarcinoma.

  2. Piperine suppresses tumor growth and metastasis in vitro and in vivo in a 4T1 murine breast cancer model

    Institute of Scientific and Technical Information of China (English)

    Li-hua LAI; Qi-hong FU; Yang LIU; Kai JIANG; Qing-ming GUO; Qing-yun CHEN; Bin YAN; Qing-qing WANG; Jian-gen SHEN

    2012-01-01

    Aim:To investigate the effects of piperine,a major pungent alkaloid present in Piper nigrum and Piper Iongum,on the tumor growth and metastasis of mouse 4T1 mammary carcinoma in vitro and in vivo,and elucidate the underlying mechanisms.Methods:Growth of 4T1 cells was assessed using MTT assay.Apoptosis and cell cycle of 4T1 cells were evaluated with flow cytometry,and the related proteins were examined using Western blotting.Real-time quantitative PCR was applied to detect the expression of matrix metalloproteinases (MMPs).A highly malignant,spontaneously metastasizing 4T1 mouse mammary carcinoma model was used to evaluate the in vivo antitumor activity.Piperine was injected into tumors every 3 d for 3 times.Results:Piperine (35-280 μmol/L)inhibited the growth of 4T1 cells in time-and dose-dependent manners (the IC50 values were 105+1.08 and 78.52+1.06 μmol/L,respectively,at 48 and 72 h).Treatment of 4T1 cells with piperine (70-280 μmol/L)dose-dependently induced apoptosis of 4T1 cells,accompanying activation of caspase 3.The cells treated with piperine (140 and 280μmol/L)significantly increased the percentage of cells in G2/M phase with a reduction in the expression of cyclin B1.Piperine (140and 280 μmol/L)significantly decreased the expression of MMP-9 and MMP-13,and inhibited 4T1 cell migration in vitro.Injection of piperine (2.5 and 5 mg/kg)dose-dependently suppressed the primary 4T1 tumor growth and injection of piperine (5 mg/kg)significantly inhibited the lung metastasis.Conclusion:These results demonstrated that piperine is an effective antitumor compound in vitro and in vivo,and has the potential to be developed as a new anticancer drug.

  3. Cancer associated fibroblasts promote tumor growth and metastasis by modulating the tumor immune microenvironment in a 4T1 murine breast cancer model.

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    Debbie Liao

    Full Text Available BACKGROUND: Local inflammation associated with solid tumors commonly results from factors released by tumor cells and the tumor stroma, and promotes tumor progression. Cancer associated fibroblasts comprise a majority of the cells found in tumor stroma and are appealing targets for cancer therapy. Here, our aim was to determine the efficacy of targeting cancer associated fibroblasts for the treatment of metastatic breast cancer. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate that cancer associated fibroblasts are key modulators of immune polarization in the tumor microenvironment of a 4T1 murine model of metastatic breast cancer. Elimination of cancer associated fibroblasts in vivo by a DNA vaccine targeted to fibroblast activation protein results in a shift of the immune microenvironment from a Th2 to Th1 polarization. This shift is characterized by increased protein expression of IL-2 and IL-7, suppressed recruitment of tumor-associated macrophages, myeloid derived suppressor cells, T regulatory cells, and decreased tumor angiogenesis and lymphangiogenesis. Additionally, the vaccine improved anti-metastatic effects of doxorubicin chemotherapy and enhanced suppression of IL-6 and IL-4 protein expression while increasing recruitment of dendritic cells and CD8(+ T cells. Treatment with the combination therapy also reduced tumor-associated Vegf, Pdgfc, and GM-CSF mRNA and protein expression. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that cancer associated fibroblasts promote tumor growth and metastasis through their role as key modulators of immune polarization in the tumor microenvironment and are valid targets for therapy of metastatic breast cancer.

  4. Murine breast carcinoma 4T1 cells are more sensitive to atranorin than normal epithelial NMuMG cells in vitro: Anticancer and hepatoprotective effects of atranorin in vivo.

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    Solár, Peter; Hrčková, Gabriela; Koptašíková, Lenka; Velebný, Samuel; Solárová, Zuzana; Bačkor, Martin

    2016-04-25

    The aim of this study was to evaluate the anticancer effect of atranorin (ATR) on murine 4T1 breast carcinoma cells and compare its sensitivity with normal mammary epithelial NMuMG cells in vitro. Anti-tumor and hepatoprotective activity of ATR-therapy was examined on mouse model of 4T1-induced cancer disease. ATR significantly reduced clonogenic ability of carcinoma 4T1 cells at the concentration of 75 μM, but clonogenicity of normal NMuMG cells was not affected by any of ATR concentrations tested. Moreover, flow cytometric and BrdU incorporation analysis did not confirm the inhibited entry into S-phase of the cell cyle after ATR incubation, and on the contrary, it induced apoptosis associated with the activation of caspase-3 and PARP cleavage in 4T1 cells. Although ATR did not cause any significant changes in Bcl-xL protein expression in NMuMG cells, an apparent depletion of Bcl-xL protein in 4T1 cells after 48 h ATR therapy was confirmed. Based on this result as well as the result of the total cell number decline, we can conclude that 4T1 cells are more sensitive to ATR therapy than NMuMG cells. ATR administration resulted in significantly longer survival time of BALB/c mice inoculated with 4T1 cells, what was associated with reduced tumor size and the higher numbers of apoptotic 4T1 cells. No differences were recorded in the number of BrdU-positive tumor cells between ATR-treated group and controls. Results indicate that ATR has rather proapoptotic than antiproliferative effect on 4T1 cells in vitro and in vivo and normal NMuMG cells are less sensitive to ATR. Furthermore, our studies revealed protective effect of ATR against oxidative stress in the livers of the tumor-bearing mice.

  5. Differential Proteome Analysis Identifies TGF-β-Related Pro-Metastatic Proteins in a 4T1 Murine Breast Cancer Model.

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    Misako Sato

    Full Text Available Transforming growth factor-β (TGF-β has a dual role in tumorigenesis, acting as either a tumor suppressor or as a pro-oncogenic factor in a context-dependent manner. Although TGF-β antagonists have been proposed as anti-metastatic therapies for patients with advanced stage cancer, how TGF-β mediates metastasis-promoting effects is poorly understood. Establishment of TGF-β-related protein expression signatures at the metastatic site could provide new mechanistic information and potentially allow identification of novel biomarkers for clinical intervention to discriminate TGF-β oncogenic effects from tumor suppressive effects. In the present study, we found that systemic administration of the TGF-β receptor kinase inhibitor, SB-431542, significantly inhibited lung metastasis from transplanted 4T1 mammary tumors in Balb/c mice. The differentially expressed proteins in the comparison of lung metastases from SB-431542 treated and control vehicle-treated groups were analyzed by a quantitative LTQ Orbitrap Velos system coupled with stable isotope dimethyl labeling. A total of 36,239 peptides from 6,694 proteins were identified, out of which 4,531 proteins were characterized as differentially expressed. A subset of upregulated proteins in the control group was validated by western blotting and immunohistochemistry. The eukaryotic initiation factor (eIF family members constituted the most enriched protein pathway in vehicle-treated compared with SB-43512-treated lung metastases, suggesting that increased protein expression of specific eIF family members, especially eIF4A1 and eEF2, is related to the metastatic phenotype of advanced breast cancer and can be down-regulated by TGF-β pathway inhibitors. Thus our proteomic approach identified eIF pathway proteins as novel potential mediators of TGF-β tumor-promoting activity.

  6. Synthesis, Characterization and in Vitro Evaluation of Manganese Ferrite (MnFe2O4) Nanoparticles for Their Biocompatibility with Murine Breast Cancer Cells (4T1).

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    Kanagesan, Samikannu; Aziz, Sidek Bin Ab; Hashim, Mansor; Ismail, Ismayadi; Tamilselvan, Subramani; Alitheen, Noorjahan Banu Binti Mohammed; Swamy, Mallappa Kumara; Purna Chandra Rao, Bandaru

    2016-03-11

    Manganese ferrite (MnFe2O4) magnetic nanoparticles were successfully prepared by a sol-gel self-combustion technique using iron nitrate and manganese nitrate, followed by calcination at 150 °C for 24 h. Calcined sample was systematically characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and vibrational sample magnetometry (VSM) in order to identify the crystalline phase, functional group, morphology, particle size, shape and magnetic behavior. It was observed that the resultant spinal ferrites obtained at low temperature exhibit single phase, nanoparticle size and good magnetic behavior. The study results have revealed the existence of a potent dose dependent cytotoxic effect of MnFe2O4 nanoparticles against 4T1 cell lines at varying concentrations with IC50 values of 210, 198 and 171 μg/mL after 24 h, 48 h and 72 h of incubation, respectively. Cells exposed to higher concentrations of nanoparticles showed a progressive increase of apoptotic and necrotic activity. Below 125 μg/mL concentration the nanoparticles were biocompatible with 4T1 cells.

  7. 4T1 Murine Mammary Carcinoma Cells Enhance Macrophage-Mediated Innate Inflammatory Responses

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    Laurence Madera; Anna Greenshields; Power Coombs, Melanie R.; Hoskin, David W.

    2015-01-01

    Tumor progression and the immune response are intricately linked. While it is known that cancers alter macrophage inflammatory responses to promote tumor progression, little is known regarding how cancers affect macrophage-dependent innate host defense. In this study, murine bone-marrow-derived macrophages (BMDM) were exposed to murine carcinoma-conditioned media prior to assessment of the macrophage inflammatory response. BMDMs exposed to 4T1 mammary carcinoma-conditioned medium demonstrated...

  8. Icaritin synergistically enhances the radiosensitivity of 4T1 breast cancer cells.

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    Jinsheng Hong

    Full Text Available Icaritin (ICT is a hydrolytic form of icariin isolated from plants of the genus Epimedium. This study was to investigate the radiosensitization effect of icaritin and its possible underlying mechanism using murine 4T1 breast cancer cells. The combination of Icaritin at 3 µM or 6 µM with 6 or 8 Gy of ionizing radiation (IR in the clonogenic assay yielded an ER (enhancement ratio of 1.18 or 1.28, CI (combination index of 0.38 or 0.19 and DRI (dose reducing index of 2.51 or 5.07, respectively. These strongly suggest that Icaritin exerted a synergistic killing (? effect with radiation on the tumor cells. This effect might relate with bioactivities of ICT: 1 exert an anti-proliferative effect in a dose- and time-dependent manner, which is different from IR killing effect but likely work together with the IR effect; 2 suppress the IR-induced activation of two survival paths, ERK1/2 and AKT; 3 induce the G2/M blockage, enhancing IR killing effect; and 4 synergize with IR to enhance cell apoptosis. In addition, ICT suppressed angiogenesis in chick embryo chorioallantoic membrane (CAM assay. Taken together, ICT is a new radiosensitizer and can enhance anti-cancer effect of IR or other therapies.

  9. Regulation of Wnt signaling activity for growth suppression induced by quercetin in 4T1 murine mammary cancer cells.

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    Kim, Haesung; Seo, Eun-Min; Sharma, Ashish R; Ganbold, Bilguun; Park, Jongbong; Sharma, Garima; Kang, Young-Hee; Song, Dong-Keun; Lee, Sang-Soo; Nam, Ju-Suk

    2013-10-01

    Quercetin is a promising chemopreventive agent against cancer that inhibits tumor progression by inducing cell cycle arrest and promoting apoptotic cell death. Recently, the Wnt/β-catenin signaling pathway has been implicated in mammary tumorigenesis, where its abnormal activation is associated with the development of breast cancer. Thus, the objective of this study was to examine the biological activities of quercetin against mammary cancer cells, and to determine whether quercetin could regulate the Wnt/β-catenin signaling pathway. Quercetin showed dose-dependent inhibition of cell growth and induced apoptosis in 4T1 cells. Treatment of 20 µM quercetin suppressed ~50% of basal TopFlash luciferase activity. Moreover, the inhibitory effect of quercetin on the Wnt/β-catenin signaling pathway was confirmed by the reduced stabilization of the β-catenin protein. Among various antagonists screened for the Wnt/β-catenin signaling pathway, the expression of DKK1, 2 and 3 was induced after treatment with 20 µM of quercetin. Stimulation with recombinant DKK1 protein, showed suppressive cell growth of mammary cancer cells instead of quercetin. When 4T1 cells were treated with recombinant Wnt3a or LiCl along with quercetin, both stimulators for the Wnt/β-catenin signaling pathway were able to restore the suppressed cell viability by quercetin. Thus, our data suggest that quercetin exerts its anticancer activity through the downregulation of Wnt/β-catenin signaling activity. These results indicate for the first time that quercetin decreases cell viability and induces apoptosis in murine mammary cancer cells, which is possibly mediated by DKK-dependent inhibition of the Wnt/β-catenin signaling pathway. In conclusion, our findings suggest that quercetin has great potential value as chemotherapeutic agent for cancer treatment, especially in breast cancer controlled by Wnt/β-catenin signaling activity.

  10. Aspirin Breaks the Crosstalk between 3T3-L1 Adipocytes and 4T1 Breast Cancer Cells by Regulating Cytokine Production.

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    Chia-Chien Hsieh

    Full Text Available Breast cancer is one of the most common cancers in women worldwide. The obesity process is normally accompanied by chronic, low-grade inflammation. Infiltration by inflammatory cytokines and immune cells provides a favorable microenvironment for tumor growth, migration, and metastasis. Epidemiological evidence has shown that aspirin is an effective agent against several types of cancer. The aim of this study is to investigate the anti-inflammatory and anti-cancer effects of aspirin on 3T3-L1 adipocytes, 4T1 murine breast cancer cells, and their crosstalk. The results showed that aspirin treatment inhibited differentiation and lipid accumulation by 3T3-L1 preadipocytes, and decreased the secretion of the inflammatory adipokine MCP-1 after stimulation with tumor necrosis factor (TNF-α or conditioned medium from RAW264.7 cells. In 4T1 cells, treatment with aspirin decreased cell viability and migration, possibly by suppressing MCP-1 and VEGF secretion. Subsequently, culture of 4T1 cells in 3T3-L1 adipocyte-conditioned medium (Ad-CM and co-culture of 3T3-L1 and 4T1 cells using a transwell plate were performed to clarify the relationship between these two cell lines. Aspirin exerted its inhibitory effects in the transwell co-culture system, as well as the conditioned-medium model. Aspirin treatment significantly inhibited the proliferation of 4T1 cells, and decreased the production of MCP-1 and PAI-1 in both the Ad-CM model and co-culture system. Aspirin inhibited inflammatory MCP-1 adipokine production by 3T3-L1 adipocytes and the cell growth and migration of 4T1 cells. It also broke the crosstalk between these two cell lines, possibly contributing to its chemopreventive properties in breast cancer. This is the first report that aspirin's chemopreventive activity supports the potential application in auxiliary therapy against obesity-related breast cancer development.

  11. Aspirin Breaks the Crosstalk between 3T3-L1 Adipocytes and 4T1 Breast Cancer Cells by Regulating Cytokine Production.

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    Hsieh, Chia-Chien; Huang, Yu-Shan

    2016-01-01

    Breast cancer is one of the most common cancers in women worldwide. The obesity process is normally accompanied by chronic, low-grade inflammation. Infiltration by inflammatory cytokines and immune cells provides a favorable microenvironment for tumor growth, migration, and metastasis. Epidemiological evidence has shown that aspirin is an effective agent against several types of cancer. The aim of this study is to investigate the anti-inflammatory and anti-cancer effects of aspirin on 3T3-L1 adipocytes, 4T1 murine breast cancer cells, and their crosstalk. The results showed that aspirin treatment inhibited differentiation and lipid accumulation by 3T3-L1 preadipocytes, and decreased the secretion of the inflammatory adipokine MCP-1 after stimulation with tumor necrosis factor (TNF)-α or conditioned medium from RAW264.7 cells. In 4T1 cells, treatment with aspirin decreased cell viability and migration, possibly by suppressing MCP-1 and VEGF secretion. Subsequently, culture of 4T1 cells in 3T3-L1 adipocyte-conditioned medium (Ad-CM) and co-culture of 3T3-L1 and 4T1 cells using a transwell plate were performed to clarify the relationship between these two cell lines. Aspirin exerted its inhibitory effects in the transwell co-culture system, as well as the conditioned-medium model. Aspirin treatment significantly inhibited the proliferation of 4T1 cells, and decreased the production of MCP-1 and PAI-1 in both the Ad-CM model and co-culture system. Aspirin inhibited inflammatory MCP-1 adipokine production by 3T3-L1 adipocytes and the cell growth and migration of 4T1 cells. It also broke the crosstalk between these two cell lines, possibly contributing to its chemopreventive properties in breast cancer. This is the first report that aspirin's chemopreventive activity supports the potential application in auxiliary therapy against obesity-related breast cancer development.

  12. Differential Contribution of Acute and Chronic Inflammation to the Development of Murine Mammary 4T1 Tumors.

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    Celso Tarso Rodrigues Viana

    Full Text Available Based on the notion that inflammation favors tumorigenesis, our experiments comparatively assessed the influence of acute and chronic inflammation on the development of a murine mammary tumor (4T1. In addition, we characterized angiogenic and inflammatory markers in the tumor tissue and systemically. Subcutaneous implantation of polyether-polyurethane sponge discs in Balb/c mice was used to host 4T1 tumor cells (1x10(6, which were inoculated intraimplant 24 h or 10 days post implantation. Flow cytometric analysis of enzyme-digested implants revealed that, after 24 hours, the population of leukocytes was primarily characterized by neutrophils (42.53% +/- 8.45 and monocytes (37.53% +/- 7.48, with some lymphocytes (16.27% +/- 4.0 and a few dendritic cells (1.82% +/- 0.36. At 10 days, macrophages were predominant (37.10% +/- 4.54, followed by lymphocytes (28.1% +/- 4.77, and monocytes (22.33% +/- 3.05, with some dendritic cells (13.60% +/- 0.55 and neutrophils (11.07% +/- 2.27. A mammary tumor grown in a chronic inflammatory environment was 2-fold when compared with one grown in acute inflammation and 5-fold when compared with tumor alone. The levels of pro-angiogenic cytokine (VEGF-Vascular Endothelial Growth Factor were higher in implant-bearing tumor when 4T1 cells were grown in 10-day old implants as compared to the VEGF levels of the two other groups. Overall, the levels of the inflammatory markers evaluated (NAG -N-acetylglucosaminidase, TNF-α-Tumor Necrosis Factor-α were higher in both groups of implant-bearing tumors and in serum from those animals when compared with the tumor alone levels. This inflammation-related difference in tumor growth may provide new insights into the contribution of different inflammatory cell populations to cancer progression.

  13. Lunasin Attenuates Obesity-Associated Metastasis of 4T1 Breast Cancer Cell through Anti-Inflammatory Property.

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    Hsieh, Chia-Chien; Wang, Chih-Hsuan; Huang, Yu-Shan

    2016-12-15

    Obesity prevalence is increasing worldwide and is accompanied by low-grade inflammation with macrophage infiltration, which is linked with a poorer breast cancer prognosis. Lunasin is a natural seed peptide with chemopreventive properties and multiple bioactivities. This is the first study to explore the chemopreventive effects of lunasin in the obesity-related breast cancer condition using 4T1 breast cancer cells, 3T3-L1 adipocytes, and conditioned media. An obesity-related environment, such as leptin-treatment or adipocyte-conditioned medium (Ad-CM), promoted 4T1 cell proliferation and metastasis. Lunasin treatment inhibited metastasis of breast cancer cells, partially through modestly inhibiting production of the angiogenesis-mediator vascular endothelial growth factor (VEGF) and significantly by inhibiting secretion in the Ad-CM condition. Subsequently, two adipocytes inflammation models, 3T3-L1 adipocytes were stimulated by tumor necrosis factor (TNF)-α, and RAW 264.7 cell-conditioned medium (RAW-CM) was used to mimic the obese microenvironment. Lunasin significantly inhibited interleukin (IL)-6 and macrophage chemoattractant protein (MCP)-1 secretion by TNF-α stimulation, and MCP-1 secretion in the RAW-CM model. This study highlights that lunasin suppressed 3T3-L1 adipocyte inflammation and inhibited 4T1 breast cancer cell migration. Interestingly, lunasin exerted more effective anti-metastasis activity in the obesity-related condition models, indicating that it possesses anti-inflammatory properties and blocks adipocyte-cancer cell cross-talk.

  14. Extract of Azadirachta indica (Neem) Leaf Induces Apoptosis in 4T1 Breast Cancer BALB/c Mice.

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    Othman, Fauziah; Motalleb, Gholamreza; Lam Tsuey Peng, Sally; Rahmat, Asmah; Fakurazi, Sharida; Pei Pei, Chong

    2011-01-01

    Azadirachta indica (Neem) has been used traditionally for many centuries. Some impressive therapeutic qualities have been discovered. However, the therapeutic effect of neem leaf extract in 4T1 breast cancer has not been documented. The purpose of the present study is to investigate the therapeutic effect of ethanolic Neem leaf extract in an in vivo 4T1 breast cancer model in mice. A total of 84 female BALB/c mice were divided randomly into 7 groups (3 non-cancerous groups and 4 cancerous groups) consisting of 12 mice per group. The 3 non-cancerous groups were normal mice treated with 0.5% of Tween 20 in phosphate buffer saline (PBS) (NC), 250 mg/kg Neem (N250) or 500 mg/kg Neem (N500). The 4 cancerous groups were; cancer controls treated with 0.5% of Tween 20 in PBS (CC), and cancerous mice treated with 0.5 µg/mL tamoxifen citrate (CT), 250 mg/kg Neem leaf extract (CN 250) or 500 mg/kg Neem leaf extract (CN 500). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were used to evaluate apoptosis (cell death) in the breast cancer tissues. SPSS software, version 14 was used for statistical analysis. Statistical significance was defined as p≤0.05. Non parametric analysis of variance (ANOVA) was performed with the Kruskal Wallis test for the TUNEL assays. Parametric data among the groups was compared using ANOVA. TUNEL assays showed that the CN 250 and CN 500 groups had a higher incidence of apoptosis compared with the cancer controls. The findings showed that neem leaf extract induces apoptosis in 4T1 breast cancer BALB/c mice.

  15. Extract of Azadirachta indica (Neem Leaf Induces Apoptosis in 4T1 Breast Cancer BALB/c Mice

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    Fauziah Othman

    2011-01-01

    Full Text Available Objective: Azadirachta indica (Neem has been used traditionally for many centuries.Some impressive therapeutic qualities have been discovered. However, the therapeuticeffect of neem leaf extract in 4T1 breast cancer has not been documented. The purposeof the present study is to investigate the therapeutic effect of ethanolic Neem leaf extractin an in vivo 4T1 breast cancer model in mice.Materials and Methods: A total of 84 female BALB/c mice were divided randomly into7 groups (3 non-cancerous groups and 4 cancerous groups consisting of 12 mice pergroup. The 3 non-cancerous groups were normal mice treated with 0.5% of Tween 20 inphosphate buffer saline (PBS (NC, 250 mg/kg Neem (N250 or 500 mg/kg Neem (N500.The 4 cancerous groups were; cancer controls treated with 0.5% of Tween 20 in PBS(CC, and cancerous mice treated with 0.5 μg/mL tamoxifen citrate (CT, 250 mg/kg Neemleaf extract (CN 250 or 500 mg/kg Neem leaf extract (CN 500. Terminal deoxynucleotidyltransferase dUTP nick end labeling (TUNEL assays were used to evaluate apoptosis(cell death in the breast cancer tissues. SPSS software, version 14 was used for statisticalanalysis. Statistical significance was defined as p<0.05. Non parametric analysis ofvariance (ANOVA was performed with the Kruskal Wallis test for the TUNEL assays.Parametric data among the groups was compared using ANOVA.Results: TUNEL assays showed that the CN 250 and CN 500 groups had a higher incidenceof apoptosis compared with the cancer controls.Conclusion: The findings showed that neem leaf extract induces apoptosis in 4T1 breastcancer BALB/c mice.

  16. Fabrication of Docetaxel Surfaced Fe3O4 Magnetite Nanoparticles and their Cytotoxicity on 4 T1 Breast Cancer Cells

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    MH Yazdi

    2012-08-01

    Full Text Available Background:In the recent years, there is an increasing attention to the using of Fe3O4 magnetite nanoparticles (MNPs as drug delivery systems. Application of this nanoparticles could profit advantages of nanomedicine to enhance biological activity of pharmaceutical ingredients. Methods:Fe3O4 MNPs were synthesised by a chemical method and characterized by transmission electron microscopy and energy-dispersive spectroscopy techniques. In the next step, docetaxel-coated Fe3O4 MNPs were prepared, using percipitation method. The surface chemistry of docetaxel-coated Fe3O4 MNPs as well as their thermal decomposition characteristics were examined using fourier transform infrared spectroscopy and thermogravimetric analyzer equipment, respectively. The cytotoxicity assay was conducted on 4 T1 breast cancer carsinoma by MTT assay to evaluate the possible in vitro antiproliferative effects of docetaxel-coated Fe3O4 MNPs. Results:During precipitation process, docetaxel molecules were precipitated on the surface of Fe3O4 MNPs by the ratio of 3:100 w/w which indicates that each milligram of coated Fe3O4 MNPs averagely contained 30 mug pure docetaxel compound. Docetaxel showed aniproliferative effects against mentioned cell line. The higestest concentartion of docetaxel (80 mug/ml caused about 80% cell death. However, the results demostarted that much lower amounts of docetaxel will be needed in combination of Fe3O4 MNPs to produce the potent antiproliferative effect compared to docetaxel alone. Dose response cytotoxicity assay of docetaxel-coated Fe3O4 MNPs against 4 T1 breast cancer cells showed that lower amount of docetaxel (0.6 mug/ml can exhibit higher cytotoxic effect against this cancer cell line (90% cell death.

  17. The immunostimulatory effect of biogenic selenium nanoparticles on the 4T1 breast cancer model: an in vivo study.

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    Yazdi, Mohammad Hossein; Mahdavi, Mehdi; Varastehmoradi, Bardia; Faramarzi, Mohammad Ali; Shahverdi, Ahmad Reza

    2012-10-01

    Selenium salts as well as elemental selenium nanoparticles are attracting the attention of researchers due to their excellent biological properties. The aim of the present work was to study immunomodulation by applying elemental Se NPs to stimulate the immune response of mice bearing 4 T1 breast cancer tumors. Six- to 8-week-old female inbred BALB/c mice were divided into two groups of test and control, each containing 15 mice. Every day, for 2 weeks prior to tumor induction, selenium nanoparticles were orally administered to the mice at a dose of 100 μg/day. Then, 1 × 10(6) cells from a 4 T1 cell line were injected subcutaneously to each mouse. Oral nanoparticle administration was continued daily for 3 weeks after tumor induction. Different immunological parameters were then evaluated including cytokine level, delayed type hypersensitivity (DTH) response as well as tumor growth and the survival rates in all treated or nontreated animals. The production of Th1 cytokines, such as IFN-γ and IL-12, in spleen cell culture was increased in the test mice-administered selenium nanoparticles. The DTH response of test mice also showed a significant increase when compared to the control mice. The survival rate was notably higher for the selenium nanoparticle-treated mice compared to the control mice. Our results suggest that selenium nanoparticle administration can result in considerable induction of the Th1 platform of immune response through the elevation of IFN-γ and IL-12 and may be a cause for better prognosis in mice with tumors.

  18. In vivo antitumor and antimetastatic effects of flavokawain B in 4T1 breast cancer cell-challenged mice

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    Abu N

    2015-03-01

    Full Text Available Nadiah Abu,1,2 Nurul Elyani Mohamed,2 Swee Keong Yeap,3 Kian Lam Lim,4 M Nadeem Akhtar,5 Aimi Jamil Zulfadli,3 Beh Boon Kee,2 Mohd Puad Abdullah,2 Abdul Rahman Omar,3 Noorjahan Banu Alitheen2 1Bright Sparks Unit, Universiti Malaya, Kuala Lumpur, Malaysia; 2Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, 3Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor Darul Ehsan, Malaysia; 4Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Lot PT, Jalan Sungai Long, Bandar Sungai Long, Cheras, Selangor, Malaysia; 5Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang, Lebuhraya Tun Razak, Kuantan Pahang, Malaysia Abstract: Flavokawain B (FKB is a naturally occurring chalcone that can be isolated through the root extracts of the kava-kava plant (Piper methysticum. It can also be synthesized chemically to increase the yield. This compound is a promising candidate as a biological agent, as it is reported to be involved in a wide range of biological activities. Furthermore, FKB was reported to have antitumorigenic effects in several cancer cell lines in vitro. However, the in vivo antitumor effects of FKB have not been reported on yet. Breast cancer is one of the major causes of cancer-related deaths in the world today. Any potential treatment should not only impede the growth of the tumor, but also modulate the immune system efficiently and inhibit the formation of secondary tumors. As presented in our study, FKB induced apoptosis in 4T1 tumors in vivo, as evidenced by the terminal deoxynucleotidyl transferase dUTP nick end labeling and hematoxylin and eosin staining of the tumor. FKB also regulated the immune system by increasing both helper and cytolytic T-cell and natural killer cell populations. In addition, FKB also enhanced the levels of interleukin 2 and interferon gamma but suppressed interleukin 1B. Apart from that, FKB was also found to inhibit

  19. Comparison of the Adipose and Luminal Mammary Gland Compartment as Orthotopic Inoculation Sites in a 4T1-Based Immunocompetent Preclinical Model for Triple-Negative Breast Cancer.

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    Steenbrugge, Jonas; Breyne, Koen; Denies, Sofie; Dekimpe, Melissa; Demeyere, Kristel; De Wever, Olivier; Vermeulen, Peter; Van Laere, Steven; Sanders, Niek N; Meyer, Evelyne

    2016-12-01

    Breast tumorigenesis is classically studied in mice by inoculating tumor cells in the fat pad, the adipose compartment of the mammary gland. Alternatively, the mammary ducts, which constitute the luminal mammary gland compartment, also provide a suitable inoculation site to induce breast cancer in murine models. The microenvironments in these compartments influence tumor cell progression, yet this effect has not been investigated in an immunocompetent context. Here, we compared both mammary gland compartments as distinct inoculation sites, taking into account the immunological aspect by inoculating 4T1 tumor cells in immunocompetent mice. Following tumor cell inoculation in the adipose compartment of non-pretreated/naive, hormonally pretreated/naive and non-pretreated/lactating mice, the primary tumors developed similarly. However, a slower onset of primary tumor growth was found after inoculations in the luminal compartment of non-pretreated/lactating mice. Despite this difference in tumor development rate, metastasis to the liver and lungs was equally observed and was accompanied by lymphatic spreading of tumor cells and progressive splenomegaly with both inoculation types. Chitinase 3-like 1 (CHI3L1) and lipocalin 2 (LCN2) served as innovative biomarkers for disease progression showing increased levels in primary tumors and sera of the non-pretreated/lactating inoculation groups. A slower increase in circulating CHI3L1 but not LCN2 levels, was observed after inoculations in the luminal compartment which corroborated the slower tumor development at this inoculation site. Our results highlight the critical impact of different mammary gland compartments on tumor development in syngeneic murine models and support the use of novel tumor progression biomarkers in an immune-competent environment.

  20. Optimizing non-invasive radiofrequency hyperthermia treatment for improving drug delivery in 4T1 mouse breast cancer model

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    Ware, Matthew J.; Krzykawska-Serda, Martyna; Chak-Shing Ho, Jason; Newton, Jared; Suki, Sarah; Law, Justin; Nguyen, Lam; Keshishian, Vazrik; Serda, Maciej; Taylor, Kimberly; Curley, Steven A.; Corr, Stuart J.

    2017-03-01

    Interactions of high-frequency radio waves (RF) with biological tissues are currently being investigated as a therapeutic platform for non-invasive cancer hyperthermia therapy. RF delivers thermal energy into tissues, which increases intra-tumoral drug perfusion and blood-flow. Herein, we describe an optical-based method to optimize the short-term treatment schedules of drug and hyperthermia administration in a 4T1 breast cancer model via RF, with the aim of maximizing drug localization and homogenous distribution within the tumor microenvironment. This method, based on the analysis of fluorescent dyes localized into the tumor, is more time, cost and resource efficient, when compared to current analytical methods for tumor-targeting drug analysis such as HPLC and LC-MS. Alexa-Albumin 647 nm fluorphore was chosen as a surrogate for nab-paclitaxel based on its similar molecular weight and albumin driven pharmacokinetics. We found that RF hyperthermia induced a 30–40% increase in Alexa-Albumin into the tumor micro-environment 24 h after treatment when compared to non-heat treated mice. Additionally, we showed that the RF method of delivering hyperthermia to tumors was more localized and uniform across the tumor mass when compared to other methods of heating. Lastly, we provided insight into some of the factors that influence the delivery of RF hyperthermia to tumors.

  1. Dietary fat increases solid tumor growth and metastasis of 4T1 murine mammary carcinoma cells and mortality in obesity-resistant BALB/c mice.

    Science.gov (United States)

    Kim, Eun Ji; Choi, Mi-Ran; Park, Heesook; Kim, Minhee; Hong, Ji Eun; Lee, Jae-Yong; Chun, Hyang Sook; Lee, Ki Won; Yoon Park, Jung Han

    2011-08-11

    High-fat diets (HFDs) are known to cause obesity and are associated with breast cancer progression and metastasis. Because obesity is associated with breast cancer progression, it is important to determine whether dietary fat per se stimulates breast cancer progression in the absence of obesity. This study investigated whether an HFD increases breast cancer growth and metastasis, as well as mortality, in obesity-resistant BALB/c mice. The 4-week-old, female BALB/c mice were fed HFD (60% kcal fat) or control diet (CD, 10% kcal fat) for 16 weeks. Subsequently, 4T1 mammary carcinoma cells were injected into the inguinal mammary fat pads of mice fed continuously on their respective diets. Cell-cycle progression, angiogenesis, and immune cells in tumor tissues, proteases and adhesion molecules in the lungs, and serum cytokine levels were analyzed with immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assay (ELISA). In vitro studies were also conducted to evaluate the effects of cytokines on 4T1 cell viability, migration, and adhesion. Spleen and gonadal fat-pad weights, tumor weight, the number and volume of tumor nodules in the lung and liver, and tumor-associated mortality were increased in the HFD group, with only slight increases in energy intake and body weight. HF feeding increased macrophage infiltration into adipose tissues, the number of lipid vacuoles and the expression of cyclin-dependent kinase (CDK)2, cyclin D1, cyclin A, Ki67, CD31, CD45, and CD68 in the tumor tissues, and elevated serum levels of complement fragment 5a (C5a), interleukin (IL)-16, macrophage colony-stimulating factor (M-CSF), soluble intercellular adhesion molecule (sICAM)-1, tissue inhibitors of metalloproteinase (TIMP)-1, leptin, and triggering receptor expressed on myeloid cells (TREM)-1. Protein levels of the urokinase-type plasminogen activator, ICAM-1, and vascular cell adhesion molecule-1 were increased, but plasminogen activator inhibitor-1 levels were

  2. Influence of BMSCs-derived exosome on proliferation and invasion of mouse breast cancer cells 4 T1 and the mechanism%BMSCs 来源的外泌体对小鼠乳腺癌细胞4 T1增殖、侵袭的影响及机制探讨

    Institute of Scientific and Technical Information of China (English)

    王丹丹; 陈建中; 亢春彦

    2015-01-01

    目的:观察骨髓间充质干细胞(BMSCs)来源的外泌体(exosome)对小鼠乳腺癌细胞4T1增殖、侵袭的影响,并探讨其可能机制。方法将小鼠乳腺癌细胞4T1随机分为3组,4T1+vehicle组仅加入400μL无血清培养基,4T1+exosome组加入400μL由无血清培养基配置的exosome,4T1+exosome+磷脂酰肌醇3激酶( PI3K)/Akt信号通路阻断剂( Y294002)组加入400μL终浓度为5μmol/mL Y294002及400μg/mL exosome的培养基。分别采用MTT法、细胞划痕实验、Western blotting法检测各组细胞增殖、迁移和侵袭能力以及PI3K/Akt信号通路相关蛋白。结果4T1+exosome组、4T1+vehicle组、4T1+exosome+Y294002组细胞增殖抑制率分别为0.713%±0.050%、0.401%±0.030%、0.459%±0.800%,4T1+exosome组分别与4T1+vehicle组、4T1+exosome+Y294002组比较,P均<0.05。4T1+exosome组、4T1+vehicle组、4T1+exosome+Y294002组细胞迁移距离分别为(388.0±36.1)、(295.0±34.2)、(275.0±63.5)μm,4T1+exosome组分别与4T1+vehicle组、4T1+exosome+Y294002组比较,P均<0.05。4T1+exosome组p-AKT、β-catenin OD值分别为0.30±0.11、0.30±0.08,4T1+vehicle组分别为1.10±0.41、0.70±0.08,4T1+exosome+Y294002组分别为0.40±0.13、0.30±0.07,4T1+exosome组分别与4T1+vehicle组、4T1+exosome+Y294002组比较,P均<0.05。结论 BMSCs来源的exosome能够增加小鼠乳腺癌细胞4T1的增殖、迁移及侵袭能力,其机制可能与上调PI3K/Akt信号通路有关。%Objective To observe the influence of bone marrow mesenchymal stem cells ( BMSCs)-derived exosome on the proliferation and invasion of mouse breast cancer cells 4T1 and to investigate the mechanism.Methods The mouse breast cancer cells 4T1 were randomly divided into three groups:4T1+vehicle group, 4T1+exosome group and 4T1+exosome+Y294002 (an

  3. Radio-photothermal therapy mediated by a single compartment nanoplatform depletes tumor initiating cells and reduces lung metastasis in the orthotopic 4T1 breast tumor model

    Science.gov (United States)

    Zhou, Min; Zhao, Jun; Tian, Mei; Song, Shaoli; Zhang, Rui; Gupta, Sanjay; Tan, Dongfeng; Shen, Haifa; Ferrari, Mauro; Li, Chun

    2015-11-01

    Tumor Initiating Cells (TICs) are resistant to radiotherapy and chemotherapy, and are believed to be responsible for tumor recurrence and metastasis. Combination therapies can overcome the limitation of conventional cancer treatments, and have demonstrated promising application in the clinic. Here, we show that dual modality radiotherapy (RT) and photothermal therapy (PTT) mediated by a single compartment nanosystem copper-64-labeled copper sulfide nanoparticles ([64Cu]CuS NPs) could suppress breast tumor metastasis through eradication of TICs. Positron electron tomography (PET) imaging and biodistribution studies showed that more than 90% of [64Cu]CuS NPs was retained in subcutaneously grown BT474 breast tumor 24 h after intratumoral (i.t.) injection, indicating the NPs are suitable for the combination therapy. Combined RT/PTT therapy resulted in significant tumor growth delay in the subcutaneous BT474 breast cancer model. Moreover, RT/PTT treatment significantly prolonged the survival of mice bearing orthotopic 4T1 breast tumors compared to no treatment, RT alone, or PTT alone. The RT/PTT combination therapy significantly reduced the number of tumor nodules in the lung and the formation of tumor mammospheres from treated 4T1 tumors. No obvious side effects of the CuS NPs were noted in the treated mice in a pilot toxicity study. Taken together, our data support the feasibility of a therapeutic approach for the suppression of tumor metastasis through localized RT/PTT therapy.Tumor Initiating Cells (TICs) are resistant to radiotherapy and chemotherapy, and are believed to be responsible for tumor recurrence and metastasis. Combination therapies can overcome the limitation of conventional cancer treatments, and have demonstrated promising application in the clinic. Here, we show that dual modality radiotherapy (RT) and photothermal therapy (PTT) mediated by a single compartment nanosystem copper-64-labeled copper sulfide nanoparticles ([64Cu]CuS NPs) could suppress

  4. Effect of Neem Leaf Extract (Azadirachta indica) on c-Myc Oncogene Expression in 4T1 Breast Cancer Cells of BALB/c Mice.

    Science.gov (United States)

    Othman, Fauziah; Motalleb, Gholamreza; Lam Tsuey Peng, Sally; Rahmat, Asmah; Basri, Rusliza; Pei Pei, Chong

    2012-01-01

    Breast cancer is the most common cause of cancer-related deaths in women both worldwide and in Malaysia. Azadirachta indica (A. Juss), commonly known as neem, is one of the most versatile medicinal plants that has gained worldwide prominence due to its medicinal properties. However, the anticancer effect of ethanolic neem leaf extract against breast cancer has not been documented. The purpose of the present study is to investigate the effect of neem leaf extract on c-Myc oncogene expression in 4T1 breast cancer BALB/c mice. In this experimental study, A total of 48 female BALB/c mice were divided randomly into four groups of 12 mice per group: i.cancer control (CC) treated with 0.5% Tween 20 in PBS, ii. 0.5 µg/mL tamoxifen citrate (CT), iii. 250 mg/kg neem leaf extract (C250), and iv. 500 mg/kg neem leaf extract (C500). in situ reverse transcription polymerase chain reaction (in situ RT-PCR) was applied to evaluate suppression of c-Myc oncogene expression in breast cancer tissue. The C500 group showed significant (pneem leaf extract.

  5. Effect of Neem Leaf Extract (Azadirachta indica on c-MycOncogene Expression in 4T1 Breast Cancer Cells of BALB/c Mice

    Directory of Open Access Journals (Sweden)

    Chong Pei Pei

    2012-01-01

    Full Text Available Objective: Breast cancer is the most common cause of cancer-related deaths in women both worldwide and in Malaysia. Azadirachta indica (A. Juss, commonly known as neem, is one of the most versatile medicinal plants that has gained worldwide prominence due to its medicinal properties. However, the anticancer effect of ethanolic neem leaf extract against breast cancer has not been documented. The purpose of the present study is to investigate the effect of neem leaf extract on c-Myc oncogene expression in 4T1 breast cancer BALB/c mice.Materials and Methods: In this experimental study, A total of 48 female BALB/c mice were divided randomly into four groups of 12 mice per group: i.cancer control (CC treated with 0.5% Tween 20 in PBS, ii. 0.5 μg/mL tamoxifen citrate (CT, iii. 250 mg/kg neem leaf extract (C250, and iv. 500 mg/kg neem leaf extract (C500. In situ reverse transcription polymerase chain reaction (in situ RT-PCR was applied to evaluate suppression of c-Myc oncogene expression in breast cancer tissue.Results: The C500 group showed significant (p<0.05 suppression of c-Myc oncogene expression compared to the CC group.Conclusion: c-Myc was found to be down regulated under the effect of 500 mg/kg ethanolicneem leaf extract.

  6. Licoricidin, an Active Compound in the Hexane/Ethanol Extract of Glycyrrhiza uralensis, Inhibits Lung Metastasis of 4T1 Murine Mammary Carcinoma Cells

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    So Young Park

    2016-06-01

    Full Text Available Licorice extracts containing glycyrrhizin exhibit anti-carcinogenic properties. Because glycyrrhizin induces severe hypokalemia and hypertension, we prepared a hexane/ethanol extract of Glycyrrhiza uralensis (HEGU that lacks glycyrrhizin, and showed that HEGU induces apoptosis and G1 cell cycle arrest and inhibits migration of DU145 human prostate cancer cells. Our previous in vitro studies identified two active components in HEGU: isoangustone A, which induces apoptosis and G1 cycle arrest, and licoricidin, which inhibits metastasis. This study examined whether HEGU and licoricidin inhibit metastasis using the 4T1 mammary cancer model. Both HEGU and licoricidin treatment reduced pulmonary metastasis and the expression of CD45, CD31, HIF-1α, iNOS, COX-2, and VEGF-A in tumor tissues. Additionally, a decrease in protein expression of VEGF-R2, VEGF-C, VEGF-R3, and LYVE-1 was noted in tumor tissues of licoricidin-treated mice. Furthermore, the blood concentrations of MMP-9, ICAM-1, VCAM-1, and VEGF-A were decreased in HEGU-treated mice. In vitro 4T1 cell culture results showed that both HEGU and licoricidin inhibited cell migration, MMP-9 secretion, and VCAM expression. The present study demonstrates that the licoricidin in HEGU inhibits lung metastasis of 4T1 mammary carcinoma cells, which may be mediated via inhibition of cancer cell migration, tumor angiogenesis, and lymphangiogenesis.

  7. Recognition of tumor antigens in 4T1 cells by natural IgM from three strains of mice with different susceptibilities to spontaneous breast cancer

    Science.gov (United States)

    Díaz-Zaragoza, Mariana; Hernández-Ávila, Ricardo; Ostoa-Saloma, Pedro

    2017-01-01

    The issue of antibody responses to tumors is potentially important to cancer immunologists. Early detection of cancer represents one of the most promising approaches to reduce the growing cancer burden. Natural immunoglobulin (Ig)M antibodies have been associated with the recognition and elimination of cancerous and precancerous cells. Using natural IgM antibodies, the present study identified a set of antigens in healthy mice from three different strains and examined whether the global patterns of antibodies are able to discriminate between a condition of more or less susceptibility to breast cancer. The current study performed two-dimensional (2D) immunoblotting to detect antigens from 4T1 cells using natural IgM from serum of healthy female mice from three different strains. The t-test was used to analyze the total number of spots. There were no significant differences in the numbers of antigens recognized in each strain. However, differences in patterns were observed on 2D immunoblots among the three strains. The reactivity patterns of natural IgM antibodies to particular antigens exhibited non-random clustering, which discriminated between strains with different susceptibilities to spontaneous breast cancer. The results demonstrated that the patterns of reactivity to defined subsets of antigens are able to provide information regarding differential diagnosis associated with breast cancer sensitivity. Therefore, it may be concluded that it is possible to segregate the IgM humoral immune response toward cancer antigens according to the genetic background of individuals. In addition, it is possible to identify the recognized antigens that allow grouping or discriminate between the different IgM antibodies expressed. The possible association between a particular antigen and cancer susceptibility requires further study, but the methodology exposed in the present study may identify potential candidates for this possible association.

  8. 石榴皮鞣花酸对4T1乳腺癌小鼠免疫功能的影响%Influence of pomegranate peel ellagic acid on immune function of mice with 4T1 breast cancer

    Institute of Scientific and Technical Information of China (English)

    张玉梅; 王家晓

    2014-01-01

    Objective It is to observe the inhibitory action of pomegranate peel ellagic acid on human 4T1 breast cancer cell and its influence on immune function in breast tumor-bearing mice. Methods The growth inhibition rate of pomegranate peel ellagic acid on 4T1 cell cultured in vitro was detected;the tumor cell apoptotic ratio was measured by flow cytometry;the changes of NK,LAK,CTL activity in spleen lymphocytes and serum TNF of tumor-bearing mice were detected after treated by pomegranate peel ellagic acid,and compared with the control group. Results The growth and formation of 4T1 cells were in-hibited by pomegranate peel ellagic acid. Flow cytometry showed that pomegranate peel ellagic acid could induce apoptosis ef-fectively. Pomegranate peel ellagic acid low-dose and high-dose groups could significantly enhance the induction of tumor-bear-ing mouse spleen lymphocytes NK,LAK and CTL activity,and the serum TNF levels were significantly increased,there were significant difference compared with the saline group or DDP group(P0. 05). Conclusion Pomegranate peel ellagic acid can in-hibit the proliferation and induce apoptosis in 4T1 cells. Pomegranate peel ellagic acid can significantly improve tumor-bearing mice induce specific anti-tumor immune response.%目的:探讨石榴皮鞣花酸对人乳腺癌4 T1细胞株生长的抑制作用及对乳腺癌荷瘤小鼠免疫功能的影响。方法测定石榴皮鞣花酸对体外培养的4 T1细胞生长的抑制率;流式细胞仪测定肿瘤细胞凋亡情况;检测应用石榴皮鞣花酸后荷瘤小鼠的脾淋巴细胞的 NK、LAK、CTL活性及血清 TNF活性改变,并与对照组比较。结果石榴皮鞣花酸抑制4T1细胞生长形成;流式细胞仪显示石榴皮鞣花酸可有效诱导细胞凋亡;石榴皮鞣花酸低剂量组和高剂量组均可明显诱导荷瘤小鼠脾淋巴细胞 NK、LAK 和 CTL 活性提高,且血清 TNF 水平明显上升,与生理盐水组、DDP组比

  9. Quantitative analysis on water-soluble metabolites of three kinds of breast carcinoma cells with 9.4T 1H-MRS%9.4T1H-MRS定量分析三种乳腺癌细胞的水溶性代谢物

    Institute of Scientific and Technical Information of China (English)

    张苗苗; 章杰; 徐志峰; 陈耀文; 陈义兵; 吴仁华

    2013-01-01

    Objective To explore the features of spectrum of water-soluble metabolites of 3 kinds of breast cancer cells in vitro with 9.4T 1 H-MRS.Methods Three kinds of human breast carcinoma cells (ZR-75-1,T47-D,SK-BR-3) were cultured and collected.The metabolites were extracted with perchloric acid and prepared for MRS analysis.1H spectra were acquired with 9.4T high resolution MRS,and the concentrations of main metabolites were quantitatively calculated.Results ZR-75-1,T47-D and SK-BR-3 breast cancer cells had characteristics of three different metabolites.The metabolic peak of lactate and choline were observed in all 3 kinds of breast cancer cells.The concentration of choline-compounds and lactate in T47-D were higher than those of ZR-75-1 and SK-BR-3.Conclusion The metabolic profiles of three subtypes of human breast carcinoma cells can be reliably detected and quantified with 9.4T MRS.The metabolic of lactate and choline-compounds of T47-D cell are higher than those of ZR-75-1 and SK-BR-3.%目的 利用9.4T磁共振频谱仪离体检测3种乳腺癌细胞的水溶性代谢物频谱特征.方法 培养获取ZR-751、T47-D及SK-BR-3乳腺癌细胞,用高氯酸提取水溶性代谢物,以9.4T高场磁共振仪检测所提取水溶性代谢物的氢质子频谱,定量计算谱线中相应代谢物的浓度并分析其特征.结果 ZR-75-1、T47-D及SK-BR-3乳腺癌细胞具有3种不同代谢物特征;3种乳腺癌细胞在乳酸及胆碱处均出现波峰,且T47-D的乳酸及胆碱浓度高于ZR-75-1和SK-BR-3.结论 利用9.4T磁共振频谱仪能获取3种乳腺癌细胞的代谢信息;T47-D乳腺癌细胞内乳酸及胆碱代谢高于ZR-75-1和SK-BR-3.

  10. Curcumin improves the therapeutic efficacy of Listeria(at)-Mage-b vaccine in correlation with improved T-cell responses in blood of a triple-negative breast cancer model 4T1.

    Science.gov (United States)

    Singh, Manisha; Ramos, Ilyssa; Asafu-Adjei, Denise; Quispe-Tintaya, Wilber; Chandra, Dinesh; Jahangir, Arthee; Zang, Xingxing; Aggarwal, Bharat B; Gravekamp, Claudia

    2013-08-01

    Success of cancer vaccination is strongly hampered by immune suppression in the tumor microenvironment (TME). Interleukin (IL)-6 is particularly and highly produced by triple-negative breast cancer (TNBC) cells, and has been considered as an important contributor to immune suppression in the TME. Therefore, we hypothesized that IL-6 reduction may improve efficacy of vaccination against TNBC cancer through improved T-cell responses. To prove this hypothesis, we investigated the effect of curcumin, an inhibitor of IL-6 production, on vaccination of a highly attenuated Listeria monocytogenes (Listeria(at)), encoding tumor-associated antigens (TAA) Mage-b in a TNBC model 4T1. Two therapeutic vaccination strategies with Listeria(at)-Mage-b and curcumin were tested. The first immunization strategy involved all Listeria(at)-Mage-b vaccinations and curcumin after tumor development. As curcumin has been consumed all over the world, the second immunization strategy involved curcumin before and all therapeutic vaccinations with Listeria(at)-Mage-b after tumor development. Here, we demonstrate that curcumin significantly improves therapeutic efficacy of Listeria(at)-Mage-b with both immunization strategies particularly against metastases in a TNBC model (4T1). The combination therapy was slightly but significantly more effective against the metastases when curcumin was administered before compared to after tumor development. With curcumin before tumor development in the combination therapy, the production of IL-6 was significantly decreased and IL-12 increased by myeloid-derived suppressor cells (MDSC), in correlation with improved CD4 and CD8 T-cell responses in blood. Our study suggests that curcumin improves the efficacy of Listeria(at)-Mage-b vaccine against metastases in TNBC model 4T1 through reversal of tumor-induced immune suppression.

  11. Silibinin and Paclitaxel Cotreatment Significantly Suppress the Activity and Lung Metastasis of Triple Negative 4T1 Mammary Tumor Cell in Mice

    Directory of Open Access Journals (Sweden)

    Bing-Ying Ho

    2012-10-01

    Full Text Available The in vitro and in vivo bioactivities of silibinin (SB, paclitaxel (PTX and SB and PTX in combination (SB+PTX against murine metastatic mammary 4T1 cancer cell line were investigated. Isobologram and combination index (CI analyses showed that SB and PTX can function synergistically in the inhibition of 4T1 cell proliferation with a CI value<1. Both SB and PTX alone or SB+PTX treatment inhibited 4T1 cell migration and motility possibly through downregulation of the serpin protease nexin-1 (PN-1 and N-cadherin expression, inhibition of matrix metalloprotease (MMP-9 activity, and upregulation of E-cadherin. Flow cytometry and Western blot analyses demonstrated that both drugs deregulated cell-cycle mediators and induced apoptosis in 4T1 cells. A real-time in vivo bioluminescence imaging system to monitor the breast cancer cell metastasis in syngeneic BALB/c mice was established using a stable 4T1pGL−COX−2/Luc cell clone carrying a COX-2 promoter driven-luciferase reporter gene. In vivo study using the allograft 4T1pGL−COX−2/Luc metastatic mouse model indicated that SB co-treated with PTX can significantly suppress lung metastasis of 4T1 cells likely through inhibiting cell proliferation and angiogenesis. Together, this study demonstrates that SB could act synergistically with PTX in 4T1 cells, providing a therapeutic option for highly metastatic triple negative breast cancer.

  12. Effects of metformin alone or in combination with compound C on proliferation and cyclinD1 expression in mouse breast cancer 4T1 cells%二甲双胍单用或联合compound C对小鼠4T1乳腺癌细胞增殖和细胞周期蛋白D1表达的影响

    Institute of Scientific and Technical Information of China (English)

    杜洪泉; 黄丽莉; 贾爱华; 蒋群龙; 张光珍; 白洁

    2014-01-01

    。结论二甲双胍可以抑制小鼠乳腺癌4T1细胞的增殖;compound C可以拮抗二甲双胍的抑制作用;二甲双胍通过激活小鼠乳腺癌4T1细胞内AMPK,下调cyclin D1蛋白表达。%Objective To evaluate the effects of metformin alone or in combination with AMPK inhibitor compound C on proliferation and cyclin D 1 expression in mouse breast cancer 4T1 cells and explore the possible role of AMPK pathway in the antitumor mechanism of metformin .Methods The mouse breast cancer 4T1 cells were cultured in vitro until the logarithm growth period , and then treated with 2.5, 5, 10, 20, 40 mmol/L metformin and 20 μmol/L compound C respectively and 20 μmol/L compound C combined with 10 mmol/L metformin for 24, 48, 72 h.CCK-8 method was used to study the effects of metformin with different concentrations, 20μmol/L compound C+10 mmol/L metformin, 20 μmol/L compound C on cell proliferation . The expression of cyclinD 1 was detected with Western blot method .Multiple group comparison was performed by F test, pairwise comparison by q test, analysis of variance for repeated measurement data before and after treatment.Results CCK-8 test showed that in vitro cell culture , at 24, 48 h after 2.5 mmol/L metformin treatment, there was no significant difference in cell survival compared with control group (24 h:F=2.87,P=0.129;48 h:F=1.63 , P=0.290 ) , but a significant difference was observed at 72 h ( F=6.40 , P=0.000 ) . at 24, 48 and 72 h after 5, 10, 20, 40 mmol/L metformin treatment, the proliferation of mouse breast cancer 4T1 cells was significantly inhibited by metformin in a dose-dependent and time-dependent manner(F=332.89, 363.54 , 352.11 , all P=0.000 ) .Meanwhile in compound C group and 10 mmol/L metformin plus compound C group, cell survival showed no significant difference compared with the control group ( F=1.08 , P=2.283;F=1.92 ,P=0.050 ) .The results in Western blot analysis , the expression of cyclin D 1 decreased with the increase of

  13. B超弹性成像监测下应用吉西他滨耐药乳腺癌细胞4T1构建裸鼠乳腺癌肝转移模型%Application of a gemcitabine-resistant variant of breast cancer cell line (4T1/Gem) to construct nude mouse models of breast cancer with hepatic metastasis under ultrasonic elastography

    Institute of Scientific and Technical Information of China (English)

    叶志东; 黄迪; 黄宇; 张强; 麦振豪; 赵俐; 古维立

    2016-01-01

    目的 构建吉西他滨耐药乳腺癌细胞4T1耐药株并建立裸鼠乳腺癌肝转移模型.方法 采用低浓度加量持续诱导法,诱导吉西他滨耐药乳腺癌细胞4T1耐药株,命名为4T1/Gem;CCK-8法测定4T14T1/Gem细胞的增殖抑制率,计算耐药指数;Western blot法检测细胞P-gp蛋白表达;B超引导下注射4T1/Gem细胞悬液诱导裸鼠肝脏成瘤;HE染色观察肿瘤组织病理情况,免疫组化法检测瘤组织ER、PR、HER2、Ki-67和P-gp蛋白的表达.结果 经过14个月的诱导成功建立4T1/Gem细胞株,可在含40μg/mL的Gem培养液中稳定生长.4T1/Gem细胞耐药指数为4T1细胞的788.547倍.与亲代相比,4T1/Gem处于G1期和G2期的细胞增加,S期细胞减少;上调P-gp蛋白的表达.4T1/Gem细胞成功建立裸鼠乳腺癌肝转移模型,瘤组织中ER、PR、HER2蛋白阴性表达,Ki-67阳性10%和P-gp蛋白阳性表达.结论 成功构建吉西他滨耐药乳腺癌细胞4T1耐药株并建立裸鼠乳腺癌肝转移模型,为开发治疗乳腺癌肝转移化疗耐药的药物提供实验基础.

  14. Thalidomide promotes leukocytosis in mice inoculated with 4T1 mammary carcinoma

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    Diego Carlos dos Reis

    2014-02-01

    Full Text Available The aim of this study was to evaluate the therapy effect of thalidomide in the 4T1 murine mammary carcinoma. 4T1 cell suspension was injected into the posterior left flank of all animals to obtain solid tumors. Five days after inoculation, the treatment group was orally administered 150 mg/kg of thalidomide for seven days. Tumors were measured every 48 hours until the end of treatment. Whole blood was collected for hematology analysis. Our results suggest that thalidomide therapy increase the number of circulating leukocytes in the 4T1 murine mammary carcinoma, and this response is accompanied by a decrease in tumor growth.

  15. A GM-CSF and CD40L bystander vaccine is effective in a murine breast cancer model

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    Soliman H

    2015-12-01

    Full Text Available Hatem Soliman,1 Melanie Mediavilla-Varela,2 Scott J Antonia,3 1Department of Women's Oncology and Experimental Therapeutics, 2Department of Immunology, 3Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, FL, USA Background: There is increasing interest in using cancer vaccines to treat breast cancer patients in the adjuvant setting to prevent recurrence in high risk situations or in combination with other immunomodulators in the advanced setting. Current peptide vaccines are limited by immunologic compatibility issues, and engineered autologous cellular vaccines are difficult to produce on a large scale. Using standardized bystander cell lines modified to secrete immune stimulating adjuvant substances can greatly enhance the ability to produce immunogenic cellular vaccines using unmodified autologous cells or allogeneic medical grade tumor cell lines as targets. We investigated the efficacy of a cellular vaccine using B78H1 bystander cell lines engineered to secrete granulocyte macrophage-colony stimulating factor and CD40 ligand (BCG in a murine model of breast cancer. Methods: Five-week-old female BALB/c mice were injected orthotopically in the mammary fat pad with 4T1 tumor cells. Treatment consisted of irradiated 4T1 ± BCG cells given subcutaneously every 4 days and was repeated three times per mouse when tumors became palpable. Tumors were measured two to three times per week for 25 days. The vaccine's activity was confirmed in a second experiment using Lewis lung carcinoma (LLC cells in C57BL/6 mice to exclude a model specific effect. Interferon-γ (IFN-γ and interleukin-2 (IL-2 enzyme-linked immunospots (ELISPOTS were performed on splenic lymphocytes incubated with 4T1 lysates along with immunohistochemistry for CD3 on tumor sections. Results: Tumor growth was significantly inhibited in the 4T1-BCG and LLC-BCG treatment groups when compared to 4T1 and LLC treatment groups. There were higher levels of IL-2 and IFN

  16. An Improved Syngeneic Orthotopic Murine Model of Human Breast Cancer Progression

    Science.gov (United States)

    Rashid, Omar M.; Nagahashi, Masayuki; Ramachandran, Suburamaniam; Dumur, Catherine; Schaum, Julia; Yamada, Akimitsu; Terracina, Krista P.; Milstien, Sheldon; Spiegel, Sarah; Takabe, Kazuaki

    2014-01-01

    Purpose Breast cancer drug development costs nearly $610 million and 37 months in preclinical mouse model trials with minimal success rates. Despite these inefficiencies, there are still no consensus breast cancer preclinical models. Methods Murine mammary adenocarcinoma 4T1-luc2 cells were implanted subcutaneous (SQ) or orthotopically percutaneous injection in the area of the nipple (OP), or surgically into the chest 2nd mammary fat pad under direct vision (ODV) in Balb/c immunocompetent mice. Tumor progression was followed by in vivo bioluminescence and direct measurements, pathology and survival determined, and tumor gene expression analyzed by genome-wide microarrays. Results ODV produced less variable sized tumors and was a reliable method of implantation. ODV implantation into the chest 2nd mammary pad rather than into the abdominal 4th mammary pad, the most common implantation site, better mimicked human breast cancer progression pattern, which correlated with bioluminescent tumor burden and survival. Compared to SQ, ODV produced tumors that differentially expressed genes whose interaction networks are of importance in cancer research. qPCR validation of 10 specific target genes of interest in ongoing clinical trials demonstrated significant differences in expression. Conclusions ODV implantation into the chest 2nd mammary pad provides the most reliable model that mimics human breast cancer compared from subcutaneous implantation that produces tumors with different genome expression profiles of clinical significance. Increased understanding of the limitations of the different preclinical models in use will help guide new investigations and may improve the efficiency of breast cancer drug development. PMID:25200444

  17. Thrombin-cleaved COOH(-) terminal osteopontin peptide binds with cyclophilin C to CD147 in murine breast cancer cells.

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    Mi, Zhiyong; Oliver, Tim; Guo, Hongtao; Gao, Chengjiang; Kuo, Paul C

    2007-05-01

    Osteopontin is a glycoprotein that has been linked to metastatic function in breast, lung, and prostate cancers. However, the mechanism by which osteopontin acts to induce metastatic properties is largely unknown. One intriguing feature of osteopontin is the presence of a conserved thrombin cleavage site that is COOH-terminal from a well-characterized RGD domain. Although the COOH-terminal fragment may bind to cell surface CD44 receptors, little is known about the COOH-terminal osteopontin fragment. In the current study, we use the murine mammary epithelial tumor cell lines 4T1 and 4T07; these cells are thioguanine-resistant sublines derived from the parental population of 410.4 cells from Balb/cfC3H mice. Using flow cytometry and Forster resonance energy transfer, we show that the COOH-terminal fragment of osteopontin binds with another marker of metastatic function (cyclophilin C or rotamase) to the CD147 cell surface glycoprotein (also known as extracellular matrix metalloproteinase inducer), to activate Akt1/2 and matrix metalloproteinase-2. In in vitro assays, thrombin cleavage of osteopontin to generate short COOH-terminal osteopontin in the presence of cyclophilin C increases migration and invasion of both 4T07 and 4T1 cells. This interaction between osteopontin peptide and cyclophilin C has not been previously described but assigns a heretofore unknown function for the thrombin-cleaved osteopontin COOH-terminal fragment.

  18. DHA诱导小鼠乳癌4T1细胞凋亡及其对死亡受体蛋白表达的影响%APOPTOSIS OF MOUSE 4TI BREAST CANCER CELL INDUCED BY DHA AND ITS DFFECTS ON EXPRESSIONS OF DEATH RECEPTORS

    Institute of Scientific and Technical Information of China (English)

    隋英忠; 薛美兰; 葛银林; 张金玉; 何信佳

    2015-01-01

    目的 研究二十二碳六烯酸(DHA)对小鼠乳癌4T1细胞凋亡的诱导作用及其对死亡受体(DR)蛋白表达的影响.方法 体外培养4T1细胞,应用MTT方法观察不同浓度的DHA对4T1细胞增殖活力的影响;Annexin V/PI双染流式细胞术分析不同浓度DHA对4T1细胞凋亡率影响;采用Western blotting方法检测DR4、DR5和肿瘤坏死因子相关凋亡诱导配体(TRAIL)表达的变化.结果 采用不同浓度DHA处理后,4T1细胞增殖活力较对照组显著下降(F=84.62,q=16.54~25.31,P<0.05);细胞凋亡率明显增高(F=287.68,q=32.74~56.58,P<0.05);DR5和TRAIL表达均明显上调(F=64.75、149.72,q=9.32~51.59,P<0.05).结论 DHA可能通过DR途径抑制小鼠4T1乳癌细胞的生长,诱导其凋亡.

  19. Elimination of Tumor Cells Using Folate Receptor Targeting by Antibody-Conjugated, Gold-Coated Magnetite Nanoparticles in a Murine Breast Cancer Model

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    Evan S. Krystofiak

    2012-01-01

    Full Text Available Background. The chemotherapeutic treatment of cancer suffers from poor specificity for targeting the tumor cells and often results in adverse effects such as systemic toxicity, damage to nontarget tissues, and development of drug-resistant tumors in patients. Increasingly, drug nanocarriers have been explored as a way of lessening or overcoming these problems. In this study, antibody-conjugated Au-coated magnetite nanoparticles, in conjunction with inductive heating produced by exposure to an oscillating magnetic field (OMF, were evaluated for their effects on the viability of tumor cells in a murine model of breast cancer. Treatment effects were evaluated by light microscopy and SEM. Results. 4T1 mammary epithelial carcinoma cells overexpressing the folate receptor were targeted with an anti-folate receptor primary antibody, followed by labeling with secondary antibody-conjugated Au-coated magnetite nanoparticles. In the absence of OMF exposure, nanoparticle labeling had no effect on 4T1 cell viability. However, following OMF treatment, many of the labeled 4T1 cells showed extensive membrane damage by SEM analysis, and dramatically reduced viability as assessed using a live/dead staining assay. Conclusions. These results demonstrate that Au-coated magnetite targeted to tumor cells through binding to an overexpressed surface receptor, in the presence of an OMF, can lead to tumor cell death.

  20. Tetrandrine Suppresses Cancer Angiogenesis and Metastasis in 4T1 Tumor Bearing Mice

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    Jian-Li Gao

    2013-01-01

    Full Text Available Metastasis remains the most deadly aspect of cancer and still evades direct treatment. Thus, there is a great need to develop new treatment regimens to suppress tumor cells that have escaped surgical removal or that may have already disseminated. We have found that tetrandrine (TET exhibits anticolon cancer activity. Here, we investigate the inhibition effect of TET to breast cancer metastasis, angiogenesis and its molecular basis underlying TET’s anticancer activity. We compare TET with chemotherapy drug doxorubicin in 4T1 tumor bearing BALB/c mice model and find that TET exhibits an anticancer metastatic and antiangiogenic activities better than those of doxorubicin. The lung metastatic sites were decreased by TET, which is confirmed by bioluminescence imaging in vivo. On the other hand, laser doppler perfusion imaging (LDI was used for measuring the blood flow of tumor in 4T1-tumor bearing mice. As a result, the local blood perfusion of tumor was markedly decreased by TET after 3 weeks. Mechanistically, TET treatment leads to a decrease in p-ERK level and an increase in NF-κB levels in HUVECs. TET also regulated metastatic and angiogenic related proteins, including vascular endothelial growth factor, hypoxia-inducible factor-1α, integrin β5, endothelial cell specific molecule-1, and intercellular adhesion molecule-1 in vivo.

  1. The Antimetastatic and Antiangiogenesis Effects of Kefir Water on Murine Breast Cancer Cells.

    Science.gov (United States)

    Zamberi, Nur Rizi; Abu, Nadiah; Mohamed, Nurul Elyani; Nordin, Noraini; Keong, Yeap Swee; Beh, Boon Kee; Zakaria, Zuki Abu Bakar; Nik Abdul Rahman, Nik Mohd Afizan; Alitheen, Noorjahan Banu

    2016-12-01

    Kefir is a unique cultured product that contains beneficial probiotics. Kefir culture from other parts of the world exhibits numerous beneficial qualities such as anti-inflammatory, immunomodulation, and anticancer effects. Nevertheless, kefir cultures from different parts of the world exert different effects because of variation in culture conditions and media. Breast cancer is the leading cancer in women, and metastasis is the major cause of death associated with breast cancer. The antimetastatic and antiangiogenic effects of kefir water made from kefir grains cultured in Malaysia were studied in 4T1 breast cancer cells. 4T1 cancer cells were treated with kefir water in vitro to assess its antimigration and anti-invasion effects. BALB/c mice were injected with 4T1 cancer cells and treated orally with kefir water for 28 days. Kefir water was cytotoxic toward 4T1 cells at IC50 (half-maximal inhibitory concentration) of 12.5 and 8.33 mg/mL for 48 and 72 hours, respectively. A significant reduction in tumor size and weight (0.9132 ± 0.219 g) and a substantial increase in helper T cells (5-fold) and cytotoxic T cells (7-fold) were observed in the kefir water-treated group. Proinflammatory and proangiogenic markers were significantly reduced in the kefir water-treated group. Kefir water inhibited tumor proliferation in vitro and in vivo mainly through cancer cell apoptosis, immunomodulation by stimulating T helper cells and cytotoxic T cells, and anti-inflammatory, antimetastatic, and antiangiogenesis effects. This study brought out the potential of the probiotic beverage kefir water in cancer treatment. © The Author(s) 2016.

  2. Antitumor and antimetastatic activities of grape skin polyphenols in a murine model of breast cancer.

    Science.gov (United States)

    Sun, T; Chen, Q Y; Wu, L J; Yao, X M; Sun, X J

    2012-10-01

    Treatment modalities are not effective once breast cancer metastasis has occurred. Dietary botanicals may have a better protective effect. We therefore investigated the effects of grape skin polyphenols on a highly metastatic mouse mammary carcinoma cell line. In vitro treatment of 4T1 cells, with grape skin polyphenols resulted in inhibition of the migration and viability in a dose-dependent manner. The migration of 4T1 cells was significantly inhibited by grape skin polyphenols, even at a very low concentration (5 μg/ml), and was totally inhibited when the concentration was 20 μg/ml. However, 20 μg/ml of grape skin polyphenols inhibited cell viability by only 11.4%. The inhibition of migration is independent of decreased cell viability or apoptosis induction. Further analysis indicated that the inhibition of migration by grape skin polyphenols is involved in blocking the PI3k/Akt and MAPK pathways. The effects of dietary grape skin polyphenols were then examined using an in vivo model in which 4T1 cells were implanted subcutaneously in Balb/c mice. The metastasis of tumor cells to the lungs was inhibited significantly by dietary grape skin extracts (0.5 and 1.0 mg/ml in drinking water) and the survival of the mice enhanced. These data suggest that grape skin polyphenols possess chemotherapeutic efficacy against breast cancer with metastases. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. A novel protein with anti-metastasis activity on 4T1 carcinoma from medicinal fungus Cordyceps militaris.

    Science.gov (United States)

    Yang, Qing; Yin, Yalin; Yu, Guojun; Jin, Yanxia; Ye, Xiangdong; Shrestha, Alok; Liu, Wei; Yu, Wenhui; Sun, Hui

    2015-09-01

    Cordyceps militaris is a famous fungus used in traditional Chinese medicine for nearly one thousand years. And its fruiting body is known to possess anticancer and immunomodulatory activities. This study describes the isolation, characterization, and test of antitumor activity of a C. militaris protein, called here as "C. militaris immunoregulatory protein" (CMIP). CMIP was purified through a three-step chromatographic procedure. The MS analyses showed that CMIP corresponded to an uncharacterized protein (CCM_01955) in the C. militaris transcriptional database. Circular dichroism of CMIP revealed the composition of 35.5% β-sheet, 18.5% α-helix, 17.0% turn and 29.0% random coil. No significant cytotoxicity of CMIP was observed on HeLa, HepG2 and 4T1 tumor cells. However, CMIP demonstrated anti-metastasis activity on a mouse model of 4T1 breast cancer lung metastasis. It reduced the number of tumor nodules in the lung of tumor-bearing mice and prolonged their survival time. Furthermore, proliferation of the 4T1 cells was inhibited by macrophage-CMIP conditioned media. And the mRNA levels of cytokines TNF-α, IL-1β and IL-6 were increased significantly in peritoneal macrophages treated by CMIP. These results reveal the antitumor potential of CMIP, thus reinforcing the importance of biochemical prospecting of C. militaris.

  4. Tocotrienol-adjuvanted dendritic cells inhibit tumor growth and metastasis: a murine model of breast cancer.

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    Sitti Rahma Abdul Hafid

    Full Text Available Tocotrienol-rich fraction (TRF from palm oil is reported to possess anti-cancer and immune-enhancing effects. In this study, TRF supplementation was used as an adjuvant to enhance the anti-cancer effects of dendritic cells (DC-based cancer vaccine in a syngeneic mouse model of breast cancer. Female BALB/c mice were inoculated with 4T1 cells in mammary pad to induce tumor. When the tumor was palpable, the mice in the experimental groups were injected subcutaneously with DC-pulsed with tumor lysate (TL from 4T1 cells (DC+TL once a week for three weeks and fed daily with 1 mg TRF or vehicle. Control mice received unpulsed DC and were fed with vehicle. The combined therapy of using DC+TL injections and TRF supplementation (DC+TL+TRF inhibited (p<0.05 tumor growth and metastasis. Splenocytes from the DC+TL+TRF group cultured with mitomycin-C (MMC-treated 4T1 cells produced higher (p<0.05 levels of IFN-γ and IL-12. The cytotoxic T-lymphocyte (CTL assay also showed enhanced tumor-specific killing (p<0.05 by CD8(+ T-lymphocytes isolated from mice in the DC+TL+TRF group. This study shows that TRF has the potential to be used as an adjuvant to enhance effectiveness of DC-based vaccines.

  5. Green tea (Camellia sinensis) extract inhibits both the metastasis and osteolytic components of mammary cancer 4T1 lesions in mice.

    Science.gov (United States)

    Luo, Ke-Wang; Ko, Chun-Hay; Yue, Grace Gar-Lee; Lee, Julia Kin-Ming; Li, Kai-Kai; Lee, Michelle; Li, Gang; Fung, Kwok-Pui; Leung, Ping-Chung; Lau, Clara Bik-San

    2014-04-01

    Green tea (Camellia sinensis, CS), a kind of Chinese tea commonly consumed as a healthy beverage, has been demonstrated to have various biological activities, including antioxidation, antiobesity and anticancer. Our study aims to investigate the antitumor, antimetastasis and antiosteolytic effects of CS aqueous extract both in vitro and in vivo using metastasis-specific mouse mammary carcinoma 4T1 cells. Our results showed that treatment of 4T1 cells with CS aqueous extract resulted in significant inhibition of 4T1 cell proliferation. CS extract induced 4T1 apoptosis in a dose-dependent manner as assessed by annexin-V and propidium iodide staining and caspase-3 activity. Western blot analysis showed that CS increased the expression of Bax-to-Bcl-2 ratio and activated caspase-8 and caspase-3 to induce apoptosis. CS also inhibited 4T1 cell migration and invasion at 0.06-0.125 mg/ml. In addition, CS extract (0.6 g/kg, orally fed daily for 4 weeks) was effective in decreasing the tumor weight by 34.8% in female BALB/c mice against water treatment control (100%). Apart from the antitumor effect, CS extract significantly decreased lung and liver metastasis in BALB/c mice bearing 4T1 tumors by 54.5% and 72.6%, respectively. Furthermore, micro-computed tomography and in vitro osteoclast staining analysis suggested that CS extract was effective in bone protection against breast cancer-induced bone destruction. In conclusion, the present study demonstrated that the CS aqueous extract, which closely mimics green tea beverage, has potent antitumor and antimetastasis effects in breast cancer and could protect the bone from breast cancer-induced bone destruction.

  6. Delivery-corrected imaging of fluorescently-labeled glucose reveals distinct metabolic phenotypes in murine breast cancer.

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    Amy E Frees

    Full Text Available When monitoring response to cancer therapy, it is important to differentiate changes in glucose tracer uptake caused by altered delivery versus a true metabolic shift. Here, we propose an optical imaging method to quantify glucose uptake and correct for in vivo delivery effects. Glucose uptake was measured using a fluorescent D-glucose derivative 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-ylAmino-2-deoxy-D-glucose (2-NBDG in mice implanted with dorsal skin flap window chambers. Additionally, vascular oxygenation (SO2 was calculated using only endogenous hemoglobin contrast. Results showed that the delivery factor proposed for correction, "RD", reported on red blood cell velocity and injected 2-NBDG dose. Delivery-corrected 2-NBDG uptake (2-NBDG60/RD inversely correlated with blood glucose in normal tissue, indicating sensitivity to glucose demand. We further applied our method in metastatic 4T1 and nonmetastatic 4T07 murine mammary adenocarcinomas. The ratio 2-NBDG60/RD was increased in 4T1 tumors relative to 4T07 tumors yet average SO2 was comparable, suggesting a shift toward a "Warburgian" (aerobic glycolysis metabolism in the metastatic 4T1 line. In heterogeneous regions of both 4T1 and 4T07, 2-NBDG60/RD increased slightly but significantly as vascular oxygenation decreased, indicative of the Pasteur effect in both tumors. These data demonstrate the utility of delivery-corrected 2-NBDG and vascular oxygenation imaging for differentiating metabolic phenotypes in vivo.

  7. Modulation of murine breast tumor vascularity, hypoxia and chemotherapeutic response by exercise.

    Science.gov (United States)

    Betof, Allison S; Lascola, Christopher D; Weitzel, Douglas; Landon, Chelsea; Scarbrough, Peter M; Devi, Gayathri R; Palmer, Gregory; Jones, Lee W; Dewhirst, Mark W

    2015-05-01

    Exercise has been shown to improve postischemia perfusion of normal tissues; we investigated whether these effects extend to solid tumors. Estrogen receptor-negative (ER-, 4T1) and ER+ (E0771) tumor cells were implanted orthotopically into syngeneic mice (BALB/c, N = 11-12 per group) randomly assigned to exercise or sedentary control. Tumor growth, perfusion, hypoxia, and components of the angiogenic and apoptotic cascades were assessed by MRI, immunohistochemistry, western blotting, and quantitative polymerase chain reaction and analyzed with one-way and repeated measures analysis of variance and linear regression. All statistical tests were two-sided. Exercise statistically significantly reduced tumor growth and was associated with a 1.4-fold increase in apoptosis (sedentary vs exercise: 1544 cells/mm(2), 95% CI = 1223 to 1865 vs 2168 cells/mm(2), 95% CI = 1620 to 2717; P = .048), increased microvessel density (P = .004), vessel maturity (P = .006) and perfusion, and reduced intratumoral hypoxia (P = .012), compared with sedentary controls. We also tested whether exercise could improve chemotherapy (cyclophosphamide) efficacy. Exercise plus chemotherapy prolonged growth delay compared with chemotherapy alone (P < .001) in the orthotopic 4T1 model (n = 17 per group). Exercise is a potential novel adjuvant treatment of breast cancer. © The Author 2015. Published by Oxford University Press.

  8. Antitumor and antimetastatic activities of a novel benzothiazole-2-thiol derivative in a murine model of breast cancer.

    Science.gov (United States)

    Hu, XiaoLin; Li, Sen; He, Yan; Ai, Ping; Wu, Shaoyong; Su, Yonglin; Li, Xiaolin; Cai, Lei; Peng, Xingchen

    2017-01-02

    The prognosis of metastatic breast cancer is always very poor. Thus, it is urgent to develop novel drugs with less toxicity against metastatic breast cancer. A new drug (XC-591) derived from benzothiazole-2-thiol was designed and synthesized in our lab. In this study, we tried to assess effects of XC-591 treatment on primary breast cancer and pulmonary metastasis in 4T1 mice model. Furthermore, we tried to discover its possible molecular mechanism of action. MTT experiment showed XC-591 had significant anti-cancer activity on diverse cancer cells. Furthermore, XC-591 significantly suppressed the proliferation of 4T1 cells by colony formation assay. The in vivo results displayed that XC-591 could inhibit the growth and metastasis in 4T1 model. Moreover, histological analysis revealed that XC-591 treatment increased apoptosis, inhibited proliferation and angiogenesis in vivo. In addition, XC-591 did not contribute to obvious drug associated toxicity during the whole study. Molecular mechanism showed XC-591 could inhibit RhoGDI, activate caspase-3 and decrease phosphorylated Akt. The present data may be important to further explore this kind of new small-molecule inhibitor.

  9. Magnetic single-walled carbon nanotubes as efficient drug delivery nanocarriers in breast cancer murine model: noninvasive monitoring using diffusion-weighted magnetic resonance imaging as sensitive imaging biomarker

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    Al Faraj A

    2014-12-01

    Full Text Available Achraf Al Faraj,1 Abjal Pasha Shaik,2 Asma Sultana Shaik1,3 1Department of Radiological Sciences, 2Department of Clinical Lab Sciences, College of Applied Medical Sciences, 3Prince Naif Health Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia Purpose: Targeting doxorubicin (DOX by means of single-walled carbon nanotube (SWCNT nanocarriers may help improve the clinical utility of this highly active therapeutic agent. Active targeting of SWCNTs using tumor-specific antibody and magnetic attraction by tagging the nanotubes with iron oxide nanoparticles can potentially reduce the unnecessary side effects and provide enhanced theranostics. In the current study, the in vitro and in vivo efficacy of DOX-loaded SWCNTs as theranostic nanoprobes was evaluated in a murine breast cancer model.Methods: Iron-tagged SWCNTs conjugated with Endoglin/CD105 antibody with or without DOX were synthetized and extensively characterized. Their biocompatibility was assessed in vitro in luciferase (Luc2-expressing 4T1 (4T1-Luc2 murine breast cancer cells using TiterTACS™ Colorimetric Apoptosis Detection Kit (apoptosis induction, poly (ADP-ribose polymerase (marker for DNA damage, and thiobarbituric acid-reactive substances (oxidative stress generation assays, and the efficacy of DOX-loaded SWCNTs was evaluated by measuring the radiance efficiency using bioluminescence imaging (BLI. Tumor progression and growth were monitored after 4T1-Luc2 cells inoculation using noninvasive BLI and magnetic resonance imaging (MRI before and after subsequent injection of SWCNT complexes actively and magnetically targeted to tumor sites.Results: Significant increases in apoptosis, DNA damage, and oxidative stress were induced by DOX-loaded SWCNTs. In addition, a tremendous decrease in bioluminescence was observed in a dose- and time-dependent manner. Noninvasive BLI and MRI revealed successful tumor growth and subsequent attenuation along with metastasis

  10. Delivery rate affects uptake of a fluorescent glucose analog in murine metastatic breast cancer.

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    Narasimhan Rajaram

    Full Text Available We demonstrate an optical strategy using intravital microscopy of dorsal skin flap window chamber models to image glucose uptake and vascular oxygenation in vivo. Glucose uptake was imaged using a fluorescent glucose analog, 2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-ylamino]-2-deoxyglucose (2-NBDG. SO2 was imaged using the differential absorption properties of oxygenated [HbO2] and deoxygenated hemoglobin [dHb]. This study was carried out on two sibling murine mammary adenocarcinoma lines, 4T1 and 4T07. 2-NBDG uptake in the 4T1 tumors was lowest when rates of delivery and clearance were lowest, indicating perfusion-limited uptake in poorly oxygenated tumor regions. For increasing rates of delivery that were still lower than the glucose consumption rate (as measured in vitro, both 2-NBDG uptake and the clearance rate from the tumor increased. When the rate of delivery of 2-NBDG exceeded the glucose consumption rate, 2-NBDG uptake decreased with any further increase in rate of delivery, but the clearance rate continued to increase. This inflection point was not observed in the 4T07 tumors due to an absence of low delivery rates close to the glucose consumption rate. In the 4T07 tumors, 2-NBDG uptake increased with increasing rates of delivery at low rates of clearance. Our results demonstrate that 2-NBDG uptake in tumors is influenced by the rates of delivery and clearance of the tracer. The rates of delivery and clearance are, in turn, dependent on vascular oxygenation of the tumors. Knowledge of the kinetics of tracer uptake as well as vascular oxygenation is essential to make an informed assessment of glucose demand of a tumor.

  11. High and low mammographic density human breast tissues maintain histological differential in murine tissue engineering chambers.

    Science.gov (United States)

    Chew, G L; Huang, D; Lin, S J; Huo, C; Blick, T; Henderson, M A; Hill, P; Cawson, J; Morrison, W A; Campbell, I G; Hopper, J L; Southey, M C; Haviv, I; Thompson, E W

    2012-08-01

    Mammographic density (MD) is the area of breast tissue that appears radiologically white on mammography. Although high MD is a strong risk factor for breast cancer, independent of BRCA1/2 mutation status, the molecular basis of high MD and its associated breast cancer risk is poorly understood. MD studies will benefit from an animal model, where hormonal, gene and drug perturbations on MD can be measured in a preclinical context. High and low MD tissues were selectively sampled by stereotactic biopsy from operative specimens of high-risk women undergoing prophylactic mastectomy. The high and low MD tissues were transferred into separate vascularised biochambers in the groins of SCID mice. Chamber material was harvested after 6 weeks for histological analyses and immunohistochemistry for cytokeratins, vimentin and a human-specific mitochondrial antigen. Within-individual analysis was performed in replicate mice, eliminating confounding by age, body mass index and process-related factors, and comparisons were made to the parental human tissue. Maintenance of differential MD post-propagation was assessed radiographically. Immunohistochemical staining confirmed the preservation of human glandular and stromal components in the murine biochambers, with maintenance of radiographic MD differential. Propagated high MD regions had higher stromal (p = 0.0002) and lower adipose (p = 0.0006) composition, reflecting the findings in the original human breast tissue, although glands appeared small and non-complex in both high and low MD groups. No significant differences were observed in glandular area (p = 0.4) or count (p = 0.4) between high and low MD biochamber tissues. Human mammary glandular and stromal tissues were viably maintained in murine biochambers, with preservation of differential radiographic density and histological features. Our study provides a murine model for future studies into the biomolecular basis of MD as a risk factor for breast cancer.

  12. Typhonium flagelliforme decreases protein expression in murine breast cancer

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    Chodidjah Chodidjah

    2015-12-01

    Full Text Available BACKGROUND Breast cancer treatment is still ineffective, having also various side effects. Breast cancer growth is affected by human epidermal growth factor receptor 2 (HER2/neu and B cell lymphoma 2 (BCL2 expression. In vitro studies on continuous culture of continuous culture of human lymphoblasts (CEMs showed that Typhonium flagelliforme (TF increases apoptosis. The objective of this study was to evaluate whether TF syrup (TFS could decrease HER2/ neu and BCL2 expression as well as breast cancer volume (BCV in mice. METHODS An experimental post-test only control group design was conducted on 18 C3H mice with breast cancers, randomly allocated to 3 groups of 6. Group 1 received 0.2 ml of distilled water. Group 2 and 3 animals were each given 0.2 ml of 40 mg/ml and 80 mg/ml TFS, respectively. The treatment was given orally once daily for 25 days. Assessment of HER2/neu and BCL2 expression was by immunohistochemistry, whereas BCV was measured by caliper. Anova and LSD were used for data analysis. RESULTS There was a significant difference in HER2/neu and BCL2 expression as well as in BCV among the treatment groups. LSD analysis showed that HER2/neu and BCL2 expression in group 3 (51.60%; 24.60% was significantly lower than in group 1 (245.40%; 114.40% as well as group 2 (235.50%; 54.20% (p=0.000. BCV in group 3 (4392.33 mm3 was significantly greater than BCV in group 1 (253.87 mm3 (p=0.002, but was not significantly different from BCV in group 2 (3667.16 mm3 (p=0.306. CONCLUSION Suplementation with TFS decreases HER2/neu and BCL2 expression. TF appears to be a promising plant demonstarting anti cancer activity.

  13. Essential roles of the interaction between cancer cell-derived chemokine, CCL4, and intra-bone CCR5-expressing fibroblasts in breast cancer bone metastasis.

    Science.gov (United States)

    Sasaki, Soichiro; Baba, Tomohisa; Nishimura, Tatsunori; Hayakawa, Yoshihiro; Hashimoto, Shin-Ichi; Gotoh, Noriko; Mukaida, Naofumi

    2016-08-01

    From a murine breast cancer cell line, 4T1, we established a subclone, 4T1.3, which consistently metastasizes to bone upon its injection into the mammary fat pad. 4T1.3 clone exhibited similar proliferation rate and migration capacity as the parental clone. However, the intra-bone injection of 4T1.3 clone caused larger tumors than that of the parental cells, accompanied with increases in fibroblast, but not osteoclast or osteoblast numbers. 4T1.3 clone displayed an enhanced expression of a chemokine, CCL4, but not its specific receptor, CCR5. CCL4 shRNA-transfection of 4T1.3 clone had few effects on its in vitro properties, but reduced the tumorigenicity arising from the intra-bone injection. Moreover, intra-bone injection of 4T1.3 clone caused smaller tumors in mice deficient in CCR5 or those receiving CCR5 antagonist than in wild-type mice. The reduced tumor formation was associated with attenuated accumulation of CCR5-positive fibroblasts expressing connective tissue growth factor (CTGF)/CCN2. Tumor cell-derived CCL4 could induce fibroblasts to express CTGF/CCN2, which could support 4T1.3 clone proliferation under hypoxic culture conditions. Thus, the CCL4-CCR5 axis can contribute to breast cancer metastasis to bone by mediating the interaction between cancer cells and fibroblasts in bone cavity.

  14. Delivery-Corrected Imaging of Fluorescently-Labeled Glucose Reveals Distinct Metabolic Phenotypes in Murine Breast Cancer

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    Frees, Amy E.; Rajaram, Narasimhan; McCachren, Samuel S.; Fontanella, Andrew N.; Dewhirst, Mark W.; Ramanujam, Nimmi

    2014-01-01

    When monitoring response to cancer therapy, it is important to differentiate changes in glucose tracer uptake caused by altered delivery versus a true metabolic shift. Here, we propose an optical imaging method to quantify glucose uptake and correct for in vivo delivery effects. Glucose uptake was measured using a fluorescent D-glucose derivative 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-deoxy-D-glucose (2-NBDG) in mice implanted with dorsal skin flap window chambers. Additionally, vascular oxygenation (SO2) was calculated using only endogenous hemoglobin contrast. Results showed that the delivery factor proposed for correction, “RD”, reported on red blood cell velocity and injected 2-NBDG dose. Delivery-corrected 2-NBDG uptake (2-NBDG60/RD) inversely correlated with blood glucose in normal tissue, indicating sensitivity to glucose demand. We further applied our method in metastatic 4T1 and nonmetastatic 4T07 murine mammary adenocarcinomas. The ratio 2-NBDG60/RD was increased in 4T1 tumors relative to 4T07 tumors yet average SO2 was comparable, suggesting a shift toward a “Warburgian” (aerobic glycolysis) metabolism in the metastatic 4T1 line. In heterogeneous regions of both 4T1 and 4T07, 2-NBDG60/RD increased slightly but significantly as vascular oxygenation decreased, indicative of the Pasteur effect in both tumors. These data demonstrate the utility of delivery-corrected 2-NBDG and vascular oxygenation imaging for differentiating metabolic phenotypes in vivo. PMID:25526261

  15. Shigella mediated depletion of macrophages in a murine breast cancer model is associated with tumor regression.

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    Katharina Galmbacher

    Full Text Available A tumor promoting role of macrophages has been described for a transgenic murine breast cancer model. In this model tumor-associated macrophages (TAMs represent a major component of the leukocytic infiltrate and are associated with tumor progression. Shigella flexneri is a bacterial pathogen known to specificly induce apotosis in macrophages. To evaluate whether Shigella-induced removal of macrophages may be sufficient for achieving tumor regression we have developed an attenuated strain of S. flexneri (M90TDeltaaroA and infected tumor bearing mice. Two mouse models were employed, xenotransplantation of a murine breast cancer cell line and spontanous breast cancer development in MMTV-HER2 transgenic mice. Quantitative analysis of bacterial tumor targeting demonstrated that attenuated, invasive Shigella flexneri primarily infected TAMs after systemic administration. A single i.v. injection of invasive M90TDeltaaroA resulted in caspase-1 dependent apoptosis of TAMs followed by a 74% reduction in tumors of transgenic MMTV-HER-2 mice 7 days post infection. TAM depletion was sustained and associated with complete tumor regression.These data support TAMs as useful targets for antitumor therapy and highlight attenuated bacterial pathogens as potential tools.

  16. Induction of Monocyte Chemoattractant Proteins in Macrophages via the Production of Granulocyte-macrophage Colony Stimulating Factor by Breast Cancer Cells

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    Teizo eYoshimura

    2016-01-01

    Full Text Available Monocyte chemoattractant protein-1 (MCP-1/CCL2 plays an important role in the initiation and progression of cancer. We previously reported that in 4T1 murine breast cancer, non-tumor stromal cells, including macrophages, were the major source of MCP-1. In the present study, we analyzed the potential mechanisms by which MCP-1 is upregulated in macrophages infiltrating 4T1 tumors. We found that cell-free culture supernatants of 4T1 cells (4T1-sup markedly upregulated MCP-1 production by peritoneal inflammatory macrophages. 4T1-sup also upregulated other MCPs, such as MCP-3/CCL7 and MCP-5/CCL12, but modestly neutrophil chemotactic chemokines, such as KC/CXCL1 or MIP-2/CXCL2. Physicochemical analysis indicated that an approximately 2 to 3 kDa 4T1 cell product was responsible for the capacity of 4T1-sup to upregulate MCP-1 expression by macrophages. A neutralizing antibody against granulocyte-macrophage-colony stimulating factor (GM-CSF, but not macrophage-colony stimulating factor, almost completely abrogated MCP-1-inducing activity of 4T1-sup, and recombinant GM-CSF potently up-regulated MCP-1 production by macrophages. The expression levels of GM-CSF in 4T1 tumors in vivo were higher than other tumors, such as Lewis lung carcinoma. Treatment of mice with anti-GM-CSF antibody significantly reduced the growth of 4T1 tumors at the injection sites but did not reduce MCP-1 production or lung metastasis in tumor-bearing mice. These results indicate that 4T1 cells have the capacity to directly up-regulate MCP-1 production by macrophages by releasing GM-CSF; however, other mechanisms are also involved in increased MCP-1 levels in the 4T1 tumor microenvironment.

  17. Cyclooxygenase-2 inhibition blocks M2 macrophage differentiation and suppresses metastasis in murine breast cancer model.

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    Yi-Rang Na

    Full Text Available Tumor cells are often associated with abundant macrophages that resemble the alternatively activated M2 subset. Tumor-associated macrophages (TAMs inhibit anti-tumor immune responses and promote metastasis. Cyclooxygenase-2 (COX-2 inhibition is known to prevent breast cancer metastasis. This study hypothesized that COX-2 inhibition affects TAM characteristics potentially relevant to tumor cell metastasis. We found that the specific COX-2 inhibitor, etodolac, inhibited human M2 macrophage differentiation, as determined by decreased CD14 and CD163 expressions and increased TNFα production. Several key metastasis-related mediators, such as vascular endothelial growth factor-A, vascular endothelial growth factor-C, and matrix metalloproteinase-9, were inhibited in the presence of etodolac as compared to untreated M2 macrophages. Murine bone marrow derived M2 macrophages also showed enhanced surface MHCII IA/IE and CD80, CD86 expressions together with enhanced TNFα expressions with etodolac treatment during differentiation. Using a BALB/c breast cancer model, we found that etodolac significantly reduced lung metastasis, possibly due to macrophages expressing increased IA/IE and TNFα, but decreased M2 macrophage-related genes expressions (Ym1, TGFβ. In conclusion, COX-2 inhibition caused loss of the M2 macrophage characteristics of TAMs and may assist prevention of breast cancer metastasis.

  18. Inhibition of FGFR signaling by PD173074 improves antitumor immunity and impairs breast cancer metastasis.

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    Ye, Tinghong; Wei, Xiawei; Yin, Tao; Xia, Yong; Li, Deliang; Shao, Bin; Song, Xuejiao; He, Sisi; Luo, Min; Gao, Xiang; He, Zhiyao; Luo, Can; Xiong, Ying; Wang, Ningyu; Zeng, Jun; Zhao, Lifeng; Shen, Guobo; Xie, Yongmei; Yu, Luoting; Wei, Yuquan

    2014-02-01

    Aberrant fibroblast growth factor (FGF) and FGF receptor (FGFR) system have been associated with breast cancer. The objectives of our study were to investigate the effects and mechanisms of FGFR inhibition on tumor growth and metastasis on breast cancer. Our studies showed that the FGFR inhibitor PD173074 decreased the viability of several human breast cancer cells, as well as 4T1 murine mammary tumor cells. Therefore, we chose 4T1 cells to study PD173074's antitumor mechanism. Flow cytometry showed that PD173074 induced 4T1 cell apoptosis in a concentration-dependent manner. Western blot demonstrated that PD173074-induced apoptosis was correlated with the inhibition of Mcl-1 and survivin. Moreover, PD173074 also significantly increased the ratio of Bax/Bcl-2. PD173074 could also block 4T1 cell migration and invasion in vitro. In 4T1 tumor-bearing mice, PD173074 significantly inhibited tumor growth without obvious side effects. Meanwhile, PD173074 functionally reduced microvessel density and proliferation index and induced tumor apoptosis. Importantly, we found that FGFR inhibition by PD173074 reduced myeloid-derived suppressor cells (MDSCs) in the blood, spleens and tumors, accompanied by the increased infiltration of CD4(+) and CD8(+) T cells in the spleens and tumors. Furthermore, PD173074 significantly inhibited breast tumor metastasis to the lung of inoculated 4T1 breast cancer cells, which was accompanied by a reduction in MDSCs. Our findings suggested that FGFR inhibition could delay breast tumor progression, impair lung metastasis and break immunosuppression by effecting on tumor microenvironment, which may provide a promising therapeutic approach for breast cancer patient.

  19. High and low frequency subharmonic imaging of angiogenesis in a murine breast cancer model.

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    Dahibawkar, Manasi; Forsberg, Mark A; Gupta, Aditi; Jaffe, Samantha; Dulin, Kelly; Eisenbrey, John R; Halldorsdottir, Valgerdur G; Forsberg, Anya I; Dave, Jaydev K; Marshall, Andrew; Machado, Priscilla; Fox, Traci B; Liu, Ji-Bin; Forsberg, Flemming

    2015-09-01

    This project compared quantifiable measures of tumor vascularity obtained from contrast-enhanced high frequency (HF) and low frequency (LF) subharmonic ultrasound imaging (SHI) to 3 immunohistochemical markers of angiogenesis in a murine breast cancer model (since angiogenesis is an important marker of malignancy and the target of many novel cancer treatments). Nineteen athymic, nude, female rats were implanted with 5×10(6) breast cancer cells (MDA-MB-231) in the mammary fat pad. The contrast agent Definity (Lantheus Medical Imaging, N Billerica, MA) was injected in a tail vein (dose: 180μl/kg) and LF pulse-inversion SHI was performed with a modified Sonix RP scanner (Analogic Ultrasound, Richmond, BC, Canada) using a L9-4 linear array (transmitting/receiving at 8/4MHz in SHI mode) followed by HF imaging with a Vevo 2100 scanner (Visualsonics, Toronto, ON, Canada) using a MS250 linear array transmitting and receiving at 24MHz. The radiofrequency data was filtered using a 4th order IIR Butterworth bandpass filter (11-13MHz) to isolate the subharmonic signal. After the experiments, specimens were stained for endothelial cells (CD31), vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2). Fractional tumor vascularity was calculated as contrast-enhanced pixels over all tumor pixels for SHI, while the relative area stained over total tumor area was calculated from specimens. Results were compared using linear regression analysis. Out of 19 rats, 16 showed tumor growth (84%) and 11 of them were successfully imaged. HF SHI demonstrated better resolution, but weaker signals than LF SHI (0.06±0.017 vs. 0.39±0.059; p<0.001). The strongest overall correlation in this breast cancer model was between HF SHI and VEGF (r=-0.38; p=0.03). In conclusion, quantifiable measures of tumor neovascularity derived from contrast-enhanced HF SHI appear to be a better method than LF SHI for monitoring angiogenesis in a murine xenograft model of breast cancer

  20. Treatment of Murine Tumor Models of Breast Adenocarcinoma by Continuous Dual-Frequency Ultrasound

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    Amir Hoshang Barati

    2009-03-01

    Full Text Available Introduction: Acoustic transient cavitation is the primary mechanism of sonochemical reaction and has potential use for tumor treatment. In this study, the in vivo anti-tumor effect of simultaneous dual-frequency ultrasound at low-level intensity (ISATA < 6 W/cm2 was investigated in a spontaneous murine model of breast adenocarcinoma in Balb/c mice. Materials and Methods: Forty tumor bearing mice were divided into four groups (10 in each group. The treated groups received 15 or 30 minutes of combined dual-frequency ultrasound in continuous mode (1 MHzcon + 150 kHzcon respectively. The control and the sham groups contained the untreated mice. The tumor growth delay parameters including tumor volume, relative tumor volume, T5 and T2 (the needed time for each tumor to reach 5 and 2 times the initial tumor volume, respectively, survival period and percent of tumor growth inhibition ratio were measured on different days after treatment. Results: The results showed that the 30 min treatment was effective in tumor growth delay and percent of tumor growth inhibitory ratio compared to the sham and the control groups. The tumor volume growth and relative volume of tumors in the same treated group showed an anti-tumor effect relative to the sham and the control groups. There was a significant difference in tumor volume growth between this 30 min treatment group and the sham group 12 days after treatment (p-value

  1. Protoporphyrin IX fluorescence for enhanced photodynamic diagnosis and photodynamic therapy in murine models of skin and breast cancer

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    Rollakanti, Kishore Reddy

    Protoporphyrin IX (PpIX) is a photosensitizing agent derived from aminolevulinic acid. PpIX accumulates specifically within target cancer cells, where it fluoresces and produces cytotoxic reactive oxygen species. Our aims were to employ PpIX fluorescence to detect squamous cell carcinoma (SCC) of the skin (Photodynamic diagnosis, PDD), and to improve treatment efficacy (Photodynamic therapy, PDT) for basal cell carcinoma (BCC) and cutaneous breast cancer. Hyperspectral imaging and a spectrometer based dosimeter system were used to detect very early SCC in UVB-irradiated murine skin, using PpIX fluorescence. Regarding PDT, we showed that low non-toxic doses of vitamin D, given before ALA application, increase tumor specific PpIX accumulation and sensitize BCC and breast cancer cells to ALA-PDT. These optical imaging methods and the combination therapy regimen (vitamin D and ALA-PDT) are promising tools for effective management of skin and breast cancer.

  2. Dynamic changes in high and low mammographic density human breast tissues maintained in murine tissue engineering chambers during various murine peripartum states and over time.

    Science.gov (United States)

    Chew, G L; Huang, D; Huo, C W; Blick, T; Hill, P; Cawson, J; Frazer, H; Southey, M D; Hopper, J L; Henderson, M A; Haviv, I; Thompson, E W

    2013-07-01

    Mammographic density (MD) is a strong heritable risk factor for breast cancer, and may decrease with increasing parity. However, the biomolecular basis for MD-associated breast cancer remains unclear, and systemic hormonal effects on MD-associated risk is poorly understood. This study assessed the effect of murine peripartum states on high and low MD tissue maintained in a xenograft model of human MD. Method High and low MD human breast tissues were precisely sampled under radiographic guidance from prophylactic mastectomy specimens of women. The high and low MD tissues were maintained in separate vascularised biochambers in nulliparous or pregnant SCID mice for 4 weeks, or mice undergoing postpartum involution or lactation for three additional weeks. High and low MD biochamber material was harvested for histologic and radiographic comparisons during various murine peripartum states. High and low MD biochamber tissues in nulliparous mice were harvested at different timepoints for histologic and radiographic comparisons. Results High MD biochamber tissues had decreased stromal (p = 0.0027), increased adipose (p = 0.0003) and a trend to increased glandular tissue areas (p = 0.076) after murine postpartum involution. Stromal areas decreased (p = 0.042), while glandular (p = 0.001) and adipose areas (p = 0.009) increased in high MD biochamber tissues during lactation. A difference in radiographic density was observed in high (p = 0.0021) or low MD biochamber tissues (p = 0.004) between nulliparous, pregnant and involution groups. No differences in tissue composition were observed in high or low MD biochamber tissues maintained for different durations, although radiographic density increased over time. Conclusion High MD biochamber tissues had measurable histologic changes after postpartum involution or lactation. Alterations in radiographic density occurred in biochamber tissues between different peripartum states and over time. These findings

  3. Construction and expression of recombinant prokaryotic vector PGEX-4T-1-BC006151 correlated with multidrug resistant of lung adenocarcinoma

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    Xuejun LI

    2008-06-01

    Full Text Available Background and objective The drug resistance to chemotherapeutics is one of the important causes of low survival rate of lung cancer patients. Our previous study has demonstrated that BC006151 is a gene correlated with multidrug resistance of adenocarcinoma of lung. The aim of this study is to clone the BC006151 gene, and to construct recombinant prokaryotic vector PGEX-4T-1-BC006151, and to express it in E. coli BL21. Methods The primer was designed with restriction endonuclease position, then amplified BC006151 by RT-PCR, cleaved BC006151 cDNA and PGEX-4T-1 by BamH and EcoR I. linked it with PGEX-4T-1. Then the two fragments were linked by T4DNA. The post-linked vector was transformed into E. coli. DH5 and then expressed. Transformed the recombinant plasmids containing the correct clone into E. coli BL21 and protein was highly effective expressed. The production of GST fusion protein was identifisd by SDS-PAGE and Western-Blotting. Results The sequence of BC006151 was amplified and identified with that published in GenBank. The prokaryotic expression plasmid PGEX-4T-1-BC006151 was constructed successfully. And a new fusion protein with relative molecular mass of 13 KD was highly effectively expressed in E. coli. Conclusion The BC006151 gene correlated with multidrug resistance of lung adenocarcinoma is successfully cloned and expressed, which is helpful for the preparation of monoclonal and polyclonal antibodies.

  4. Exon-level transcriptome profiling in murine breast cancer reveals splicing changes specific to tumors with different metastatic abilities.

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    Amandine Bemmo

    Full Text Available BACKGROUND: Breast cancer is the second most frequent type of cancer affecting women. We are increasingly aware that changes in mRNA splicing are associated with various characteristics of cancer. The most deadly aspect of cancer is metastasis, the process by which cancer spreads from the primary tumor to distant organs. However, little is known specifically about the involvement of alternative splicing in the formation of macroscopic metastases. Our study investigates transcript isoform changes that characterize tumors of different abilities to form growing metastases. METHODS AND FINDINGS: To identify alternative splicing events (ASEs that are associated with the fully metastatic phenotype in breast cancer, we used Affymetrix Exon Microarrays to profile mRNA isoform variations genome-wide in weakly metastatic (168FARN and 4T07 and highly metastatic (4T1 mammary carcinomas. Statistical analysis identified significant expression changes in 7606 out of 155,994 (4% exons and in 1725 out of 189,460 (1% intronic regions, which affect 2623 out of 16,654 (16% genes. These changes correspond to putative alternative isoforms-several of which are novel-that are differentially expressed between tumors of varying metastatic phenotypes. Gene pathway analysis showed that 1224 of genes expressing alternative isoforms were involved in cell growth, cell interactions, cell proliferation, cell migration and cell death and have been previously linked to cancers and genetic disorders. We chose ten predicted splice variants for RT-PCR validation, eight of which were successfully confirmed (MED24, MFI2, SRRT, CD44, CLK1 and HNRNPH1. These include three novel intron retentions in CD44, a gene in which isoform variations have been previously associated with the metastasis of several cancers. CONCLUSION: Our findings reveal that various genes are differently spliced and/or expressed in association with the metastatic phenotype of tumor cells. Identification of

  5. Reductions in Myeloid-Derived Suppressor Cells and Lung Metastases using AZD4547 Treatment of a Metastatic Murine Breast Tumor Model

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    Li Liu

    2014-03-01

    Full Text Available Background: AZD4547, a small-molecule inhibitor targeting the tyrosine kinase of Fibroblast Growth Factor Receptors (FGFRs, is currently under phase II clinical study for human subjects having breast cancer, while the underlying mechanism remains elusive. The aim of this study is to explore the potential mechanism by which AZD4547 inhibits breast tumor lung metastases at the level of the tumor microenvironment. Methods: First, through in vitro experiments, we investigated the efficacy of the FGFRs inhibitor AZD4547 on 4T1 tumor cells for their proliferation, apoptosis, migration, and invasion. Second, by in vivo animal experiments, we evaluated the effects of AZD4547 on tumor growth and lung metastases in 4T1 tumor-bearing mice. Finally, we examined the impact of AZD4547 on the infiltration of myeloid-derived suppressor cells (MDSCs in lung, spleens, peripheral blood and tumor. Results: Through this study we found that AZD4547 could efficiently suppress tumor 4T1 cells through restraining their proliferation, blocking migration and invasion, and inducing apoptosis in vitro. In animal model we also demonstrated that AZD4547 was able to inhibit tumor growth and lung metastases, consistent with the decreased MDSCs accumulation in the tumor and lung tissues, respectively. Moreover, the reduced number of MDSCs in peripheral blood and spleens were also observed in the AZD4547-treated mice. Importantly, through the AZD4547 treatment, the CD4+ and CD8+ T-cells were significantly increased in tumor and spleens. Conclusion: Our studies showed that AZD4547 can inhibit breast cancer cell proliferation, induce its apoptosis and block migration and invasion in vitro and suppress tumor growth and lung metastases by modulating the tumor immunologic microenvironment in vivo.

  6. Antitumor effect of conditioned media derived from murine MSCs and 5-aminolevulinic acid (5-ALA) mediated photodynamic therapy in breast cancer in vitro.

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    Mohammadpour, Hemn; Majidzadeh-A, Keivan

    2015-06-01

    Mesenchymal stem cells are multi-potent progenitor cells that inhibit tumor growth by some ligands and releasing factors including TRAIL, DKK-1 and DKK-3. On other hands, photodynamic therapy is commonly used for treatment of different types of cancer. The aims of this study are to investigate of MSCs conditioned media and ALA mediated photodynamic therapy in breast cancer. Condition media was derived after documentation of mouse adipose derived MSCs. For photodynamic therapy (PDT), ALA was used at the final concentrations of 1mM for 4-h followed by exposure to red light with a peak wave length of 632-nm, delivered from diode laser located at 2 cm to achieve a total light dose of 5 Joules (J)/cm(2). Apoptosis and growth of 4T1 cancer cells were analyzed in different groups including MSCs derived condition media, PDT and MSCs derived condition media plus PDT by flow cytometry. Growth of cancer cells were assessed using MTT test. Our findings showed expression of TRAIL on mouse adipose-derived MSCs surfaces. Furthermore, treatment of 4T1 cancer cells with MSCs conditioned media cause to inhibit the cancer cells growth. Also, MSCs conditioned media with PDT have significantly synergic effects to induce apoptosis in breast cancer cells (P photodynamic therapy. This study showed that MSCs conditioned media combined with PDT may be useful as a novel treatment modality into the development of therapeutic strategies for treatment of breast cancer. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Rapamycin Promotes Mouse 4T1 Tumor Metastasis that Can Be Reversed by a Dendritic Cell-Based Vaccine.

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    Lin, Tien-Jen; Liang, Wen-Miin; Hsiao, Pei-Wen; M S, Pradeep; Wei, Wen-Chi; Lin, Hsin-Ting; Yin, Shu-Yi; Yang, Ning-Sun

    2015-01-01

    Suppression of tumor metastasis is a key strategy for successful cancer interventions. Previous studies indicated that rapamycin (sirolimus) may promote tumor regression activity or enhance immune response against tumor targets. However, rapamycin also exhibits immunosuppressant effects and is hence used clinically as an organ transplantation drug. We hypothesized that the immunosuppressive activities of rapamycin might also negatively mediate host immunity, resulting in promotion of tumor metastasis. In this study, the effects of rapamycin and phytochemical shikonin were investigated in vitro and in vivo in a 4T1 mouse mammary tumor model through quantitative assessment of immunogenic cell death (ICD), autophagy, tumor growth and metastasis. Tumor-bearing mice were immunized with test vaccines to monitor their effect on tumor metastasis. We found that intraperitoneal (ip) administration of rapamycin after a tumor-resection surgery drastically increased the metastatic activity of 4T1 tumors. Possible correlation of this finding to human cancers was suggested by epidemiological analysis of data from Taiwan's National Health Insurance Research Database (NHIRD). Since our previous studies showed that modified tumor cell lysate (TCL)-pulsed, dendritic cell (DC)-based cancer vaccines can effectively suppress metastasis in mouse tumor models, we assessed whether such vaccines may help offset this rapamycin-promoted metastasis. We observed that shikonin efficiently induced ICD of 4T1 cells in culture, and DC vaccines pulsed with shikonin-treated TCL (SK-TCL-DC) significantly suppressed rapamycin-enhanced metastasis and Treg cell expansion in test mice. In conclusion, rapamycin treatment in mice (and perhaps in humans) promotes metastasis and the effect may be offset by treatment with a DC-based cancer vaccine.

  8. Near-infrared imaging of adoptive immune cell therapy in breast cancer model using cell membrane labeling.

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    Fatma M Youniss

    Full Text Available The overall objective of this study is to non-invasively image and assess tumor targeting and retention of directly labeled T-lymphocytes following their adoptive transfer in mice. T-lymphocytes obtained from draining lymph nodes of 4T1 (murine breast cancer cell sensitized BALB/C mice were activated in-vitro with Bryostatin/Ionomycin for 18 hours, and were grown in the presence of Interleukin-2 for 6 days. T-lymphocytes were then directly labeled with 1,1-dioctadecyltetramethyl indotricarbocyanine Iodide (DiR, a lipophilic near infrared fluorescent dye that labels the cell membrane. Assays for viability, proliferation, and function of labeled T-lymphocytes showed that they were unaffected by DiR labeling. The DiR labeled cells were injected via tail vein in mice bearing 4T1 tumors in the flank. In some cases labeled 4T1 specific T-lymphocytes were injected a week before 4T1 tumor cell implantation. Multi-spectral in vivo fluorescence imaging was done to subtract the autofluorescence and isolate the near infrared signal carried by the T-lymphocytes. In recipient mice with established 4T1 tumors, labeled 4T1 specific T-lymphocytes showed marked tumor retention, which peaked 6 days post infusion and persisted at the tumor site for up to 3 weeks. When 4T1 tumor cells were implanted 1-week post-infusion of labeled T-lymphocytes, T-lymphocytes responded to the immunologic challenge and accumulated at the site of 4T1 cell implantation within two hours and the signal persisted for 2 more weeks. Tumor accumulation of labeled 4T1 specific T-lymphocytes was absent in mice bearing Meth A sarcoma tumors. When lysate of 4T1 specific labeled T-lymphocytes was injected into 4T1 tumor bearing mice the near infrared signal was not detected at the tumor site. In conclusion, our validated results confirm that the near infrared signal detected at the tumor site represents the DiR labeled 4T1 specific viable T-lymphocytes and their response to immunologic challenge

  9. Silencing of GM3 synthase suppresses lung metastasis of murine breast cancer cells

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    Gu, Yuchao; ZHANG, JUNHUA; Mi, Wenyi; Yang, Jing; Han, Feng; Lu, Xinzhi; Yu, Wengong

    2008-01-01

    Background Gangliosides are sialic acid containing glycosphingolipids that are ubiquitously distributed on vertebrate plasma membranes. GM3, a precursor for most of the more complex ganglioside species, is synthesized by GM3 synthase. Although total ganglioside levels are significantly higher in breast tumor tissue than in normal mammary tissue, the roles played by gangliosides in breast cancer formation and metastasis are not clear. Methods To investigate the roles of gangliosides in breast ...

  10. Doxorubicin in Combination with a Small TGFβ Inhibitor: A Potential Novel Therapy for Metastatic Breast Cancer in Mouse Models

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    Bandyopadhyay, Abhik; Wang, Long; Agyin, Joseph; Tang, Yuping; Lin, Shu; Yeh, I-Tien; De, Keya; Sun, Lu-Zhe

    2010-01-01

    Background Recent studies suggested that induction of epithelial-mesenchymal transition (EMT) might confer both metastatic and self-renewal properties to breast tumor cells resulting in drug resistance and tumor recurrence. TGFβ is a potent inducer of EMT and has been shown to promote tumor progression in various breast cancer cell and animal models. Principal Findings We report that chemotherapeutic drug doxorubicin activates TGFβ signaling in human and murine breast cancer cells. Doxorubicin induced EMT, promoted invasion and enhanced generation of cells with stem cell phenotype in murine 4T1 breast cancer cells in vitro, which were significantly inhibited by a TGFβ type I receptor kinase inhibitor (TβRI-KI). We investigated the potential synergistic anti-tumor activity of TβR1-KI in combination with doxorubicin in animal models of metastatic breast cancer. Combination of Doxorubicin and TβRI-KI enhanced the efficacy of doxorubicin in reducing tumor growth and lung metastasis in the 4T1 orthotopic xenograft model in comparison to single treatments. Doxorubicin treatment alone enhanced metastasis to lung in the human breast cancer MDA-MB-231 orthotopic xenograft model and metastasis to bone in the 4T1 orthotopic xenograft model, which was significantly blocked when TβR1-KI was administered in combination with doxorubicin. Conclusions These observations suggest that the adverse activation of TGFβ pathway by chemotherapeutics in the cancer cells together with elevated TGFβ levels in tumor microenvironment may lead to EMT and generation of cancer stem cells resulting in the resistance to the chemotherapy. Our results indicate that the combination treatment of doxorubicin with a TGFβ inhibitor has the potential to reduce the dose and consequently the toxic side-effects of doxorubicin, and improve its efficacy in the inhibition of breast cancer growth and metastasis. PMID:20442777

  11. Doxorubicin in combination with a small TGFbeta inhibitor: a potential novel therapy for metastatic breast cancer in mouse models.

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    Abhik Bandyopadhyay

    Full Text Available BACKGROUND: Recent studies suggested that induction of epithelial-mesenchymal transition (EMT might confer both metastatic and self-renewal properties to breast tumor cells resulting in drug resistance and tumor recurrence. TGFbeta is a potent inducer of EMT and has been shown to promote tumor progression in various breast cancer cell and animal models. PRINCIPAL FINDINGS: We report that chemotherapeutic drug doxorubicin activates TGFbeta signaling in human and murine breast cancer cells. Doxorubicin induced EMT, promoted invasion and enhanced generation of cells with stem cell phenotype in murine 4T1 breast cancer cells in vitro, which were significantly inhibited by a TGFbeta type I receptor kinase inhibitor (TbetaRI-KI. We investigated the potential synergistic anti-tumor activity of TbetaR1-KI in combination with doxorubicin in animal models of metastatic breast cancer. Combination of Doxorubicin and TbetaRI-KI enhanced the efficacy of doxorubicin in reducing tumor growth and lung metastasis in the 4T1 orthotopic xenograft model in comparison to single treatments. Doxorubicin treatment alone enhanced metastasis to lung in the human breast cancer MDA-MB-231 orthotopic xenograft model and metastasis to bone in the 4T1 orthotopic xenograft model, which was significantly blocked when TbetaR1-KI was administered in combination with doxorubicin. CONCLUSIONS: These observations suggest that the adverse activation of TGFbeta pathway by chemotherapeutics in the cancer cells together with elevated TGFbeta levels in tumor microenvironment may lead to EMT and generation of cancer stem cells resulting in the resistance to the chemotherapy. Our results indicate that the combination treatment of doxorubicin with a TGFbeta inhibitor has the potential to reduce the dose and consequently the toxic side-effects of doxorubicin, and improve its efficacy in the inhibition of breast cancer growth and metastasis.

  12. Gene expression in tumor cells and stroma in dsRed 4T1 tumors in eGFP-expressing mice with and without enhanced oxygenation

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    Moen Ingrid

    2012-01-01

    Full Text Available Abstract Background The tumor microenvironment is pivotal in tumor progression. Thus, we aimed to develop a mammary tumor model to elucidate molecular characteristics in the stroma versus the tumor cell compartment by global gene expression. Secondly, since tumor hypoxia influences several aspects of tumor pathophysiology, we hypothesized that hyperoxia might have an inhibitory effect on tumor growth per se. Finally, we aimed to identify differences in gene expression and key molecular mechanisms, both in the native state and following treatment. Methods 4T1 dsRed breast cancer cells were injected into eGFP expressing NOD/SCID mice. Group 1 was exposed to 3 intermittent HBO treatments (Day 1, 4 and 7, Group 2 to 7 daily HBO treatments (both 2.5bar, 100% O2, à 90 min, whereas the controls were exposed to a normal atmosphere. Tumor growth, histology, vascularisation, cell proliferation, cell death and metastasis were assessed. Fluorescence-activated cell sorting was used to separate tumor cells from stromal cells prior to gene expression analysis. Results The purity of sorted cells was verified by fluorescence microscopy. Gene expression profiling demonstrated that highly expressed genes in the untreated tumor stroma included constituents of the extracellular matrix and matrix metalloproteinases. Tumor growth was significantly inhibited by HBO, and the MAPK pathway was found to be significantly reduced. Immunohistochemistry indicated a significantly reduced microvessel density after intermittent HBO, whereas daily HBO did not show a similar effect. The anti-angiogenic response was reflected in the expression trends of angiogenic factors. Conclusions The present in vivo mammary tumor model enabled us to separate tumor and stromal cells, and demonstrated that the two compartments are characterized by distinct gene expressions, both in the native state and following HBO treatments. Furthermore, hyperoxia induced a significant tumor growth

  13. Pre-osteoblastic MC3T3-E1 cells promote breast cancer growth in bone in a murine xenograft model

    Institute of Scientific and Technical Information of China (English)

    Thomas M. Bodenstine; Benjamin H. Beck; Xuemei Cao; Leah M. Cook; Aimen Ismai; J. Kent Powers; Andrea M. Mastro; Danny R. Welch

    2011-01-01

    The bones are the most common sites of breast cancer metastasis. Upon arrival within the bone microenvironment, breast cancer cells coordinate the activities of stromal cells, resulting in an increase in osteoclast activity and bone matrix degradation. In late stages of bone metastasis, breast cancer cells induce apoptosis in osteoblasts, which further exacerbates bone loss. However, in early stages, breast cancer cells induce osteoblasts to secrete inflammatory cytokines purported to drive tumor progression. To more thoroughly evaluate the role of osteoblasts in early stages of breast cancer metastasis to the bones, we used green fluorescent protein-labeled human breast cancer cell lines MDA-MB-231 and MDA-MB-435, which both induce osteolysis after intra-femoral injection in athymic mice, and the murine pre-osteoblastic cell line MC3T3-E1 to modulate osteoblast populations at the sites of breast cancer metastasis. Breast cancer cells were injected directly into the femur with or without equal numbers of MC3T3-E1 cells. Tumors grew significantly larger when co-injected with breast cancer cells and MC3T3-E1 cells than injected with breast cancer cells alone. Osteolysis was induced in both groups, indicating that MC3T3-E1 cells did not block the ability of breast cancer cells to cause bone destruction. MC3T3-E1 cells promoted tumor growth out of the bone into the extraosseous stroma. These data suggest that breast cancer cells and osteoblasts communicate during early stages of bone metastasis and promote tumor growth.

  14. Blood clot formation does not affect metastasis formation or tumor growth in a murine model of breast cancer.

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    Stephanie Rossnagl

    Full Text Available Cancer is associated with increased fracture risk, due either to metastasis or associated osteoporosis. After a fracture, blood clots form. Because proteins of the coagulation cascade and activated platelets promote cancer development, a fracture in patients with cancer often raises the question whether it is a pathologic fracture or whether the fracture itself might promote the formation of metastatic lesions. We therefore examined whether blood clot formation results in increased metastasis in a murine model of experimental breast cancer metastasis. For this purpose, a clot was surgically induced in the bone marrow of the left tibia of immundeficient mice. Either one minute prior to or five minutes after clot induction, human cancer cells were introduced in the circulation by intracardiac injection. The number of cancer cells that homed to the intervention site was determined by quantitative real-time PCR and flow cytometry. Metastasis formation and longitudinal growth were evaluated by bioluminescence imaging. The number of cancer cells that homed to the intervention site after 24 hours was similar to the number of cells in the opposite tibia that did not undergo clot induction. This effect was confirmed using two more cancer cell lines. Furthermore, no difference in the number of macroscopic lesions or their growth could be detected. In the control group 72% developed a lesion in the left tibia. In the experimental groups with clot formation 79% and 65% developed lesions in the left tibia (p = ns when comparing each experimental group with the controls. Survival was similar too. In summary, the growth factors accumulating in a clot/hematoma are neither enough to promote cancer cell homing nor support growth in an experimental model of breast cancer bone metastasis. This suggests that blood clot formation, as occurs in traumatic fractures, surgical interventions, and bruises, does not increase the risk of metastasis formation.

  15. Human glandular organoid formation in murine engineering chambers after collagenase digestion and flow cytometry isolation of normal human breast tissue single cells.

    Science.gov (United States)

    Huo, Cecilia W; Huang, Dexing; Chew, Grace L; Hill, Prue; Vohora, Ambika; Ingman, Wendy V; Glynn, Danielle J; Godde, Nathan; Henderson, Michael A; Thompson, Erik W; Britt, Kara L

    2016-11-01

    Women with high mammographic density (MD) are at increased risk of breast cancer (BC) after adjustment for age and body mass index. We have developed a murine biochamber model in which both high MD (HMD) and low MD (LMD) tissue can be propagated. Here, we tested whether cells isolated by collagenase digestion and fluorescence-activated cell sorting (FACS) from normal breast can be reconstituted in our biochamber model, which would allow cell-specific manipulations to be tested. Fresh breast tissue was collected from women (n = 7) undergoing prophylactic mastectomy. The tissue underwent collagenase digestion overnight and, in some cases, additional FACS enrichment to obtain mature epithelial, luminal progenitor, mammary stem, and stromal cells. Cells were then transferred bilaterally into biochambers in SCID mice (n = 5-7) and incubated for 6 weeks, before harvesting for histological analyses, and immunohistochemical staining for cytokeratins (CK), vimentin, Ki-67, murine macrophages, and Cleaved Caspase-3. Biochambers inoculated with single cells after collagenase digestion or with flow cytometry contained glandular structures of human origin (human vimentin-positive), which expressed CK-14 and pan-CK, and were proliferating (Ki-67-positive). Glandular structures from the digested tissues were smaller than those in chambers seeded with finely chopped intact mammary tissue. Mouse macrophage infiltration was higher in the chambers arising from digested tissues. Pooled single cells and FACS fractionated cells were viable in the murine biochambers and formed proliferating glandular organoids of human origin. This is among the first report to demonstrate the success of formed human glandular organoids from isolated primary mammary cells in the murine biochamber model.

  16. Endothelial protein C receptor function in murine and human breast cancer development.

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    Florence Schaffner

    Full Text Available Several markers identify cancer stem cell-like populations, but little is known about the functional roles of stem cell surface receptors in tumor progression. Here, we show that the endothelial protein C receptor (EPCR, a stem cell marker in hematopoietic, neuronal and epithelial cells, is crucial for breast cancer growth in the orthotopic microenvironment of the mammary gland. Mice with a hypomorphic allele of EPCR show reduced tumor growth in the PyMT-model of spontaneous breast cancer development and deletion of EPCR in established PyMT tumor cells significantly attenuates transplanted tumor take and growth. We find expansion of EPCR(+ cancer stem cell-like populations in aggressive, mammary fat pad-enhanced human triple negative breast cancer cells. In this model, EPCR-expressing cells have markedly increased mammosphere- and tumor-cell initiating activity compared to another stable progenitor-like subpopulation present at comparable frequency. We show that receptor blocking antibodies to EPCR specifically attenuate in vivo tumor growth initiated by either EPCR(+ cells or the heterogenous mixture of EPCR(+ and EPCR(- cells. Furthermore, we have identified tumor associated macrophages as a major source for recognized ligands of EPCR, suggesting a novel mechanism by which cancer stem cell-like populations are regulated by innate immune cells in the tumor microenvironment.

  17. Optical metabolic imaging measures early drug response in an allograft murine breast cancer model (Conference Presentation)

    Science.gov (United States)

    Sharick, Joe T.; Cook, Rebecca S.; Skala, Melissa C.

    2017-02-01

    Previous work has shown that cellular-level Optical Metabolic Imaging (OMI) of organoids derived from human breast cancer cell-line xenografts accurately and rapidly predicts in vivo response to therapy. To validate OMI as a predictive measure of treatment response in an immune-competent model, we used the polyomavirus middle-T (PyVmT) transgenic mouse breast cancer model. The PyVmT model includes intra-tumoral heterogeneity and a complex tumor microenvironment that can influence treatment responses. Three-dimensional organoids generated from primary PyVmT tumor tissue were treated with a chemotherapy (paclitaxel) and a PI3K inhibitor (XL147), each alone or in combination. Cellular subpopulations of response were measured using the OMI Index, a composite endpoint of metabolic response comprised of the optical redox ratio (ratio of the fluorescence intensities of metabolic co-enzymes NAD(P)H to FAD) as well as the fluorescence lifetimes of NAD(P)H and FAD. Combination treatment significantly decreased the OMI Index of PyVmT tumor organoids (padaptive immunity. Thus, this method is promising for use in humans to predict long-term treatment responses accurately and rapidly, and could aid in clinical treatment planning.

  18. Expression of complement C5a receptor and the viability of 4T1 tumor cells following agonist–antagonist treatment

    Directory of Open Access Journals (Sweden)

    Nurneqman Nashreq Kosni

    2016-01-01

    Conclusion: This experiment shows the presence of C5a receptor on 4T1 cell line. We believe that the antagonist peptide is eligible to be used widely in cancer immunotherapy field; but in vivo studies need to be carried out first in the future, as it will determine how these drugs affect the tumor cell growth.

  19. Radiation-induced lung damage promotes breast cancer lung-metastasis through CXCR4 signaling

    Science.gov (United States)

    Feys, Lynn; Descamps, Benedicte; Vanhove, Christian; Vral, Anne; Veldeman, Liv; Vermeulen, Stefan; De Wagter, Carlos; Bracke, Marc; De Wever, Olivier

    2015-01-01

    Radiotherapy is a mainstay in the postoperative treatment of breast cancer as it reduces the risks of local recurrence and mortality after both conservative surgery and mastectomy. Despite recent efforts to decrease irradiation volumes through accelerated partial irradiation techniques, late cardiac and pulmonary toxicity still occurs after breast irradiation. The importance of this pulmonary injury towards lung metastasis is unclear. Preirradiation of lung epithelial cells induces DNA damage, p53 activation and a secretome enriched in the chemokines SDF-1/CXCL12 and MIF. Irradiated lung epithelial cells stimulate adhesion, spreading, growth, and (transendothelial) migration of human MDA-MB-231 and murine 4T1 breast cancer cells. These metastasis-associated cellular activities were largely mimicked by recombinant CXCL12 and MIF. Moreover, an allosteric inhibitor of the CXCR4 receptor prevented the metastasis-associated cellular activities stimulated by the secretome of irradiated lung epithelial cells. Furthermore, partial (10%) irradiation of the right lung significantly stimulated breast cancer lung-specific metastasis in the syngeneic, orthotopic 4T1 breast cancer model. Our results warrant further investigation of the potential pro-metastatic effects of radiation and indicate the need to develop efficient drugs that will be successful in combination with radiotherapy to prevent therapy-induced spread of cancer cells. PMID:26396176

  20. Effects of Tamoxifen and oestrogen on histology and radiographic density in high and low mammographic density human breast tissues maintained in murine tissue engineering chambers.

    Science.gov (United States)

    Chew, G L; Huo, C W; Huang, D; Blick, T; Hill, P; Cawson, J; Frazer, H; Southey, M C; Hopper, J L; Britt, K; Henderson, M A; Haviv, I; Thompson, E W

    2014-11-01

    Mammographic density (MD) is a strong risk factor for breast cancer. It is altered by exogenous endocrine treatments, including hormone replacement therapy and Tamoxifen. Such agents also modify breast cancer (BC) risk. However, the biomolecular basis of how systemic endocrine therapy modifies MD and MD-associated BC risk is poorly understood. This study aims to determine whether our xenograft biochamber model can be used to study the effectiveness of therapies aimed at modulating MD, by examine the effects of Tamoxifen and oestrogen on histologic and radiographic changes in high and low MD tissues maintained within the biochamber model. High and low MD human tissues were precisely sampled under radiographic guidance from prophylactic mastectomy fresh specimens of high-risk women, then inserted into separate vascularized murine biochambers. The murine hosts were concurrently implanted with Tamoxifen, oestrogen or placebo pellets, and the high and low MD biochamber tissues maintained in the murine host environment for 3 months, before the high and low MD biochamber tissues were harvested for histologic and radiographic analyses. The radiographic density of high MD tissue maintained in murine biochambers was decreased in Tamoxifen-treated mice compared to oestrogen-treated mice (p = 0.02). Tamoxifen treatment of high MD tissue in SCID mice led to a decrease in stromal (p = 0.009), and an increase in adipose (p = 0.023) percent areas, compared to placebo-treated mice. No histologic or radiographic differences were observed in low MD biochamber tissue with any treatment. High MD biochamber tissues maintained in mice implanted with Tamoxifen, oestrogen or placebo pellets had dynamic and measurable histologic compositional and radiographic changes. This further validates the dynamic nature of the MD xenograft model, and suggests the biochamber model may be useful for assessing the underlying molecular pathways of Tamoxifen-reduced MD, and in testing of other

  1. A Multifaceted Role for Myd88-Dependent Signaling in Progression of Murine Mammary Carcinoma

    Science.gov (United States)

    Higgins, Mary J.; Serrano, Antonio; Boateng, Kofi Y.; Parsons, Victoria A.; Phuong, Tiffany; Seifert, Alyssa; Ricca, Jacob M.; Tucker, Kyle C.; Eidelman, Alec S.; Carey, Maureen A.; Kurt, Robert A.

    2016-01-01

    Previous data obtained in our laboratory suggested that there may be constitutive signaling through the myeloid differentiation primary response gene 88 (Myd88)-dependent signaling cascade in murine mammary carcinoma. Here, we extended these findings by showing that, in the absence of an added Toll-like receptor (TLR) agonist, the myddosome complex was preformed in 4T1 tumor cells, and that Myd88 influenced cytoplasmic extracellular signal–regulated kinase (Erk)1/Erk2 levels, nuclear levels of nuclear factor-kappaB (NFκB) and signal transducer and activator of transcription 5 (STAT5), tumor-derived chemokine (C–C motif) ligand 2 (CCL2) expression, and in vitro and in vivo tumor growth. In addition, RNA-sequencing revealed that Myd88-dependent signaling enhanced the expression of genes that could contribute to breast cancer progression and genes previously associated with poor outcome for patients with breast cancer, in addition to suppressing the expression of genes capable of inhibiting breast cancer progression. Yet, Myd88-dependent signaling in tumor cells also suppressed expression of genes that could contribute to tumor progression. Collectively, these data revealed a multifaceted role for Myd88-dependent signaling in murine mammary carcinoma. PMID:27812285

  2. Targeting Metabolic Remodeling in Triple Negative Breast Cancer in a Murine Model

    Science.gov (United States)

    García-Castillo, Verónica; López-Urrutia, Eduardo; Villanueva-Sánchez, Octavio; Ávila-Rodríguez, Miguel Á.; Zentella-Dehesa, Alejandro; Cortés-González, Carlo; López-Camarillo, César; Jacobo-Herrera, Nadia J; Pérez-Plasencia, Carlos

    2017-01-01

    Background: Chemotherapy is the backbone of systemic treatment for triple negative breast cancer (TNBC), which is one of the most relevant breast cancers molecular types due to the ability of tumor cells to develop drug resistance, highlighting the urgent need to design newer and safer drug combinations for treatment. In this context, to overcome tumor cell drug resistance, we employed a novel combinatorial treatment including Doxorubicin, Metformin, and Sodium Oxamate (DoxMetOx). Such pharmacological combination targets indispensable hallmarks of cancer-related to aerobic glycolysis and DNA synthesis. Materials and Methods: Thirty-five female nude mice were transplanted subcutaneously with MDA-MB-231 triple negative human cancer cell line. Once tumors were visible, mice were treated with doxorubicin, metformin, oxamate or all possible pharmacologic combinations. Treatments were administered daily for 15 days and tumors were measured by calipers every day. MicroPET images were taken in three different occasions, basal state, in the middle of the treatment, and at the end of treatment. Western blot analyses, qRT-PCR, flow cytometry, and cytotoxicity assays were performed to elucidate the mechanism of cell death promoted by the drugs in vitro. Results: In this work we assessed the proof of concept of metabolic correction in solid tumors as an effective drug treatment; hence, mice bearing tumors treated with the DoxMetOx therapy showed a complete inhibition of the tumor mass growing in 15 days of treatment depicted by the micro PET images. In vitro studies displayed that the three drugs together act by inhibiting both, mTOR-phosphorylation and expression of LDH-A gene, promoting apoptosis via dependent on the caspase-3 pathway, accompanied by cleavage of PARP. Moreover, induction of autophagy process was observed by the accumulation of LC3-II, a primordial protein implicated in the conformation and elongation of the autophagolysosome. Conclusions: The lack of

  3. The effect of lipocisplatin on cisplatin efficacy and nephrotoxicity in malignant breast cancer treatment.

    Science.gov (United States)

    Li, Qun; Tian, Yuantong; Li, Dandi; Sun, Jianfeng; Shi, Donglei; Fang, Lin; Gao, Yong; Liu, Haiyan

    2014-08-01

    A lipid-cisplatin conjugate was synthesized for super-molecular assembly with lipids to form a new generation of liposomal cisplatin formulation, lipocisplatin. In vitro, lipocisplatin has higher efficacy in human ovarian cancer A2780 and human breast cancer MCF-7 with the murine breast cancer cell line 4T1 which is currently an established model for stage IV breast cancer as the most sensitive strain. Moreover, lipocisplatin demonstrated a greater MTD value and relatively longer blood circulation as compared to cisplatin. Lipocisplatin preferentially accumulate drugs to the tumor site, resulting in a better tumor inhibition efficacy. Moreover, lipocisplatin exceeds the size cutoff for kidney clearance, hence it bypasses the nephrotoxicity of cisplatin which is a major curse of one of the most efficient anticancer drugs nowadays in clinic. The results here indicated lipocisplatin may be translated into a new generation of liposomal based cisplatin drug in clinic.

  4. Expression of a phosphorylated substrate domain of p130Cas promotes PyMT-induced c-Src-dependent murine breast cancer progression.

    Science.gov (United States)

    Zhao, Yingshe; Kumbrink, Joerg; Lin, Bor-Tyh; Bouton, Amy H; Yang, Shi; Toselli, Paul A; Kirsch, Kathrin H

    2013-12-01

    Elevated expression of p130Cas (Crk-associated substrate)/BCAR1 (breast cancer antiestrogen resistance 1) in human breast tumors is a marker of poor prognosis and poor overall survival. p130Cas is a downstream target of the tyrosine kinase c-Src. Signaling mediated by p130Cas through its phosphorylated substrate domain (SD) and interaction with effector molecules directly promotes tumor progression. We previously developed a constitutively phosphorylated p130Cas SD molecule, Src*/SD (formerly referred to as Src*/CasSD), which acts as decoy molecule and attenuates the transformed phenotype in v-crk-transformed murine fibroblasts and human breast cancer cells. To test the function of this molecule in vivo, we established mouse mammary tumor virus (MMTV)-long terminal repeat-Src*/SD transgenic mice in which mammary gland development and tumor formation were analyzed. Transgenic expression of the Src*/SD molecule under the MMTV-long terminal repeat promoter did not interfere with normal mammary gland development or induce tumors in mice observed for up to 11 months. To evaluate the effects of the Src*/SD molecule on tumor development in vivo, we utilized the MMTV-polyoma middle T-antigen (PyMT) murine breast cancer model that depends on c-Src. PyMT mice crossed with Src*/SD mice displayed accelerated tumor formation. The earlier onset of tumors can be explained by the interaction of the Src* domain with PyMT and targeting the fused phosphorylated SD to the membrane. At membrane compartments, it might integrate membrane-associated active signaling complexes leading to increased proliferation measured by phospho-Histone H3 staining. Although these results were unexpected, they emphasize the importance of preventing the membrane association of Src*/SD when employed as decoy molecule.

  5. STC1 expression is associated with tumor growth and metastasis in breast cancer.

    Science.gov (United States)

    Chang, Andy C-M; Doherty, Judy; Huschtscha, Lily I; Redvers, Richard; Restall, Christina; Reddel, Roger R; Anderson, Robin L

    2015-01-01

    Stanniocalcin-1 (STC1) is a secreted glycoprotein implicated in several pathologies including retinal degeneration, cerebral ischemia, angiogenesis and inflammation. Aberrant STC1 expression has been reported in breast cancer but the significance of this is not clear. High levels of STC1 expression were found in the aggressive 4T1 murine mammary tumor cells and in the MDA-MB-231 human breast cancer line. To investigate its significance, stable clones with STC1 down-regulation using shRNA were generated in both tumor models. The consequences of STC1 down-regulation on cell proliferation, chemotactic invasion, tumor growth and metastasis were assessed. Down-regulation of STC1 in the 4T1 murine mammary tumor cells had a major impact on mammary tumor growth. This observation was replicated in a second tumor model with the MDA-MB-231 human breast cancer line, with a significant reduction in primary tumor formation and a major inhibition of metastasis as well. Interestingly, in both models, proliferation in vitro was not affected. Subsequent microarray gene expression profiling identified 30 genes to be significantly altered by STC1 down-regulation, the majority of which are associated with known hallmarks of carcinogenesis. Furthermore, bioinformatic analysis of breast cancer datasets revealed that high expression of STC1 is associated with poor survival. This is the first study to show definitively that STC1 plays an oncogenic role in breast cancer, and indicates that STC1 could be a potential therapeutic target for treatment of breast cancer patients.

  6. Inhibition of Spontaneous Breast Cancer Metastasis by Anti—Thomsen-Friedenreich Antigen Monoclonal Antibody JAA-F11

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    Jamie Heimburg

    2006-11-01

    Full Text Available Thomsen-Friedenreich antigen (TF-Ag is expressed in many carcinomas, including those of the breast, colon, bladder, prostate. TF-Ag is important in adhesion and metastasis and as a potential immunotherapy target. We hypothesized that passive transfer of JAAF11, an anti -TF-Ag monoclonal antibody, may create a survival advantage for patients with TIF-Ag -expressing tumors by cytotoxicity, blocking of tumor cell adhesion, inhibition of metastasis. This was tested using in vitro models of tumor cell growth; cytotoxicity assays; in vitro, ex vivo, in vivo models of cancer metastasis; and, finally, in vivo effects in mice with metastatic breast cancer. Unlike some anti-TF-Ag antibodies, JAA-F11 did not enhance breast carcinoma cell growth. JAA-F11 did not induce the killing of 4T1 tumor cells through complement-dependent cytotoxicity or apoptotic mechanisms. However, JAA-F11 blocked the stages of metastasis that involve the adhesion of human breast carcinoma cells to human endothelial cells (human umbilical vein endothelial cells and human bone marrow endothelial cells 60 in in vitro static adhesion models, in a perfused ex vivo model, in murine lung vasculature in an in vivo metastatic deposit formation assay. JAA-F11 significantly extended the median survival time of animals bearing metastatic 4T1 breast tumors and caused a > 50% inhibition of lung metastasis.

  7. Doxorubicin-enriched, ALDHbr mouse breast cancer stem cells are treatable to oncolytic herpes simplex virus type 1

    Directory of Open Access Journals (Sweden)

    Zhuang Xiufen

    2012-11-01

    Full Text Available Abstract Background The primary objective of this study was to test whether oncolytic herpes simplex virus type 1 (HSV1 could eradicate chemoresistant cancer stem cells (CSCs. Methods The fluorescent aldefluor reagent-based technique was used to identify and isolate ALDHbr cells as CSCs from the 4T1 murine breast cancer cell line. The presence of ALDHbr 4T1 cells was also examined in 4T1 breast cancer transplanted in immune-competent syngeneic mice. Results Compared with ALDHlo cells, ALDHbr cells had a markedly higher ability to form tumor spheres in vitro and a higher tumorigenic potential in vivo. ALDHbr cells also exhibited increased doxorubicin resistance in vitro, which correlated with a selective increase in the percentage of ALDHbr cells after doxorubicin treatment and an increased expression of P-glycoprotein (P-gp, a known chemoresistance factor. In contrast, oncolytic HSV1 was able to kill ALDHbr cells in vitro and even more markedly in vivo. Furthermore, in in vivo studies, systemic administration of doxorubicin followed by intratumoral injection of oncolytic HSV1 resulted in much more significant suppression of tumor growth with increased median survival period compared with each treatment given alone (p+ T lymphocytes were induced by oncolytic HSV1, no significant specific T cell response against CSCs was detected in vivo. Conclusions These results suggested that the use of oncolytic HSV1 following doxorubicin treatment may help eradicate residual chemoresistant CSCs in vivo.

  8. A survey on anticancer effects of artemisinin, iron, miconazole, and butyric acid on 5637 (bladder cancer and 4T1 (Breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Amir Ali Shahbazfar

    2014-01-01

    The groups treated with miconazole showed identical changes, with less severity compared to combination therapy groups. In butyric acid-treated groups, the only detectable changes were, mild cell swelling, few apoptosis, and rare necrosis. Conclusions: A combination therapy with artemisinin can be more effective against cancer cells than monotherapy with that. Butyric acid was not effective on cancer cells. Miconazole deviated the nature of cell death from apoptosis to necrosis and it must be used under caution.

  9. Dopamine D2 receptor antagonist sulpiride enhances dexamethasone responses in the treatment of drug-resistant and metastatic breast cancer.

    Science.gov (United States)

    Li, Jian; Yao, Qing-Yu; Xue, Jun-Sheng; Wang, Li-Jie; Yuan, Yin; Tian, Xiu-Yun; Su, Hong; Wang, Si-Yuan; Chen, Wen-Jun; Lu, Wei; Zhou, Tian-Yan

    2017-09-01

    Recent evidence shows that dopamine D2-like receptor (D2DR) antagonists, such as trifluoperazine and thioridazine, are effective for cancer therapy and inhibition of cancer stem-like cells (CSCs). In this study, we investigated the anti-cancer effects of combination therapy of dexamethasone (DEX) and sulpiride (SUL), an atypical antipsychotic, against drug-resistant and metastatic breast cancers and further explored the underlying mechanisms. Oral administration of SUL (25, 100 mg·kg(-1)·d(-1)) alone did not inhibit the tumor growth in human breast cancer MCF-7/Adr xenograft model, but dose-dependently decreased the proportion of CSCs in vitro and in vivo. In contrast, combination therapy of SUL (50 mg·kg(-1)·d(-1)) and DEX (8 mg·kg(-1)·d(-1)) markedly suppressed the tumor growth in MCF-7/Adr xenograft model with little systemic toxicity and lung metastasis in murine metastatic breast cancer 4T1 xenograft model. Among the metastasis-associated biomarkers analyzed, the combination therapy significantly decreased the levels of MMP-2, but increased E-cadherin levels in 4T1 xenograft tumors. Moreover, the combination therapy significantly inhibited the cell colony formation, migration and invasion of 4T1 and human breast cancer MDA-MB-231 cells in vitro. Addition of a specific D2DR agonist 7-OH-DPAT to the combination therapy reversed the enhanced anti-cancer effects in vivo and CSC population loss in tumor tissues. Our data demonstrate that SUL remarkably enhances the efficacy of DEX in the treatment of drug-resistant and metastatic breast cancer via the antagonism of D2DR, which might result from the eradication of CSCs.

  10. Breast regression protein-39 (BRP-39) promotes dendritic cell maturation in vitro and enhances Th2 inflammation in murine model of asthma

    Institute of Scientific and Technical Information of China (English)

    Qian xu; Shou-jie CHAI; Ying-ying QIAN; Min ZHANG; Kai WANG

    2012-01-01

    Aim: To determine the roles of breast regression protein-39 (BRP-39) in regulating dendritic cell maturation and in pathology of acute asthma.Methods: Mouse bone marrow-derived dendritic cells (BMDCs) were prepared,and infected with adenovirus over-expressing BRP-39.Ovalbumin (OVA)-induced murine model of acute asthma was made in female BALB/c mice by sensitizing and challenging with chicken OVA and Imject Alum.The transfected BMDCs were adoptively transferred into OVA-treated mice via intravenous injection.Airway hyperresponsiveness (AHR),inflammation and pulmonary histopathology were characterized.Results: The expression of BRP-39 mRNA and protein was significantly increased in lung tissues of OVA-treated mice.The BMDCs infected with adenovirus BRP-39 exhibited greater maturation and higher activity in vitro.Adoptive transfer of the cells into OVA-treated mice significantly augmented OVA-induced AHR and eosinophilic inflammation.Meanwhile,BRP-39 further enhanced the production of OVA-induced Th2 cytokines IL-4,IL-5,and IL-13,but significantly attenuated OVA-induced IFN-γ production in bronchoalveolar lavage fluid.Conclusion: In OVA-induced murine model of acute asthma,BRP-39 is over-expressed in lung tissue and augments Th2 inflammatory response and AHR.BRP-39 promotes dendritic cell maturation in vitro.Therefore,BRP-39 may be a potential therapeutic target of asthma.

  11. Intralesional injection of rose bengal induces a systemic tumor-specific immune response in murine models of melanoma and breast cancer.

    Directory of Open Access Journals (Sweden)

    Paul Toomey

    Full Text Available Intralesional (IL injection of PV-10 has shown to induce regression of both injected and non-injected lesions in patients with melanoma. To determine an underlying immune mechanism, the murine B16 melanoma model and the MT-901 breast cancer model were utilized. In BALB/c mice bearing MT-901 breast cancer, injection of PV-10 led to regression of injected and untreated contralateral subcutaneous lesions. In a murine model of melanoma, B16 cells were injected into C57BL/6 mice to establish one subcutaneous tumor and multiple lung lesions. Treatment of the subcutaneous lesion with a single injection of IL PV-10 led to regression of the injected lesion as well as the distant B16 melanoma lung metastases. Anti-tumor immune responses were measured in splenocytes collected from mice treated with IL PBS or PV-10. Splenocytes isolated from tumor bearing mice treated with IL PV-10 demonstrated enhanced tumor-specific IFN-gamma production compared to splenocytes from PBS-treated mice in both models. In addition, a significant increase in lysis of B16 cells by T cells isolated after PV-10 treatment was observed. Transfer of T cells isolated from tumor-bearing mice treated with IL PV-10 led to tumor regression in mice bearing B16 melanoma. These studies establish that IL PV-10 therapy induces tumor-specific T cell-mediated immunity in multiple histologic subtypes and support the concept of combining IL PV10 with immunotherapy for advanced malignancies.

  12. Disrupting Na+,HCO3--cotransporter NBCn1 (Slc4a7) delays murine breast cancer development

    DEFF Research Database (Denmark)

    Lee, S.; Axelsen, T. V.; Andersen, Anne Poder

    2016-01-01

    ) mice. Breast cancer histopathology in NBCn1 KO mice differed from that in WT mice and included less aggressive tumor types. The extracellular tumor microenvironment in NBCn1 KO mice contained higher concentrations of glucose and lower concentrations of lactate than that in WT mice. Independently......Increased metabolism and insufficient blood supply cause acidic waste product accumulation in solid cancers. During carcinogenesis, cellular acid extrusion is upregulated but the underlying molecular mechanisms and their consequences for cancer growth and progression have not been established....... Genome-wide association studies have indicated a possible link between the Na(+),HCO3(-)-cotransporter NBCn1 (SLC4A7) and breast cancer. We tested the functional consequences of NBCn1 knockout (KO) for breast cancer development. NBCn1 protein expression increased 2.5-fold during breast carcinogenesis...

  13. Metabolic reprogramming underlies metastatic potential in an obesity-responsive murine model of metastatic triple negative breast cancer.

    Science.gov (United States)

    O'Flanagan, Ciara H; Rossi, Emily L; McDonell, Shannon B; Chen, Xuewen; Tsai, Yi-Hsuan; Parker, Joel S; Usary, Jerry; Perou, Charles M; Hursting, Stephen D

    2017-01-01

    The vast majority of cancer-related deaths are due to metastatic disease, whereby primary tumor cells disseminate and colonize distal sites within the body. Triple negative breast cancer typically displays aberrant Wnt signaling, lacks effective targeted therapies, and compared with other breast cancer subtypes, is more likely to recur and metastasize. We developed a Wnt-driven lung metastasis model of triple negative breast cancer (metM-Wnt(lung)) through serial passaging of our previously described, nonmetastatic, claudin-low M-Wnt cell line. metM-Wnt(lung) cells displayed characteristics of epithelial-to-mesenchymal transition (e.g., increased invasiveness) with some re-epithealization (e.g., increased adhesion, tight colony formation, increased E-cadherin expression, and decreased Vimentin and Fibronectin expression). When orthotopically transplanted into syngeneic mice, metM-Wnt(lung) cells readily formed tumors and metastasized in vivo, and tumor growth and metastasis were enhanced in obese mice compared with non-obese mice. Gene expression analysis revealed several genes and pathways altered in metM-Wnt(lung) cells compared with M-Wnt cells, including multiple genes associated with epithelial-to-mesenchymal transition, energy metabolism and inflammation. Moreover, obesity caused significant transcriptomic changes, especially in metabolic pathways. Metabolic flux analyses showed greater metabolic plasticity, with heightened mitochondrial and glycolytic energetics in metM-Wnt(lung) cells relative to M-Wnt cells. Similar metabolic profiles were found in a second triple negative breast cancer progression series, M6 and M6C cells. These findings suggest that metabolic reprogramming is a feature of metastatic potential in triple negative breast cancer. Thus, targeting metastases-associated metabolic perturbations may represent a novel strategy for reducing the burden of metastatic triple negative breast cancer, particularly in obese women.

  14. CD4+ and CD8+ T cells have opposing roles in breast cancer progression and outcome

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    Zhang, Qunyuan; Ye, Jian; Wang, Fang; Zhang, Yanping; Hunborg, Pamela; Varvares, Mark A.; Hoft, Daniel F.; Hsueh, Eddy C.; Peng, Guangyong

    2015-01-01

    The Cancer Immunoediting concept has provided critical insights suggesting dual functions of immune system during the cancer initiation and development. However, the dynamics and roles of CD4+ and CD8+ T cells in the pathogenesis of breast cancer remain unclear. Here we utilized two murine breast cancer models (4T1 and E0771) and demonstrated that both CD4+ and CD8+ T cells were increased and involved in immune responses, but with distinct dynamic trends in breast cancer development. In addition to cell number increases, CD4+ T cells changed their dominant subsets from Th1 in the early stages to Treg and Th17 cells in the late stages of the cancer progression. We also analyzed CD4+ and CD8+ T cell infiltration in primary breast cancer tissues from cancer patients. We observed that CD8+ T cells are the key effector cell population mediating effective anti-tumor immunity resulting in better clinical outcomes. In contrast, intra-tumoral CD4+ T cells have negative prognostic effects on breast cancer patient outcomes. These studies indicate that CD4+ and CD8+ T cells have opposing roles in breast cancer progression and outcomes, which provides new insights relevant for the development of effective cancer immunotherapeutic approaches. PMID:25968569

  15. Is tail vein injection a relevant breast cancer lung metastasis model?

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    Rashid, Omar M.; Nagahashi, Masayuki; Ramachandran, Suburamaniam; Dumur, Catherine I.; Schaum, Julia C.; Yamada, Akimitsu; Aoyagi, Tomoyoshi; Milstien, Sheldon; Spiegel, Sarah

    2013-01-01

    Background Two most commonly used animal models for studying breast cancer lung metastasis are: lung metastasis after orthotopic implantation of cells into the mammary gland, and lung implantations produced after tail vein (TV) injection of cells. Tail vein injection can produce lung lesions faster, but little has been studied regarding the differences between these tumors, thus, we examined their morphology and gene expression profiles. Methods Syngeneic murine mammary adenocarcinoma, 4T1-luc2 cells, were implanted either subcutaneously (Sq), orthotopically (OS), or injected via TV in Balb/c mice. Genome-wide microarray analyses of cultured 4T1 cells, Sq tumor, OS tumor, lung metastases after OS (LMet), and lung tumors after TV (TVt) were performed 10 days after implantation. Results Bioluminescence analysis demonstrated different morphology of metastases between LMet and TVt, confirmed by histology. Gene expression profile of cells were significantly different from tumors, OS, Sq, TVt or LMet (10,350 probe sets; FDR≤1%; P1.5-fold-change; P<0.01), with no significant difference between TVt and LMet. Conclusions There were significant differences between the gene profiles of cells in culture and OS versus LMet, but there were no differences between LMet versus TVt. Therefore, the lung tumor generated by TVt can be considered genetically similar to those produced after OS, and thus TVt is a relevant model for breast cancer lung metastasis. PMID:23991292

  16. The CC chemokine CK beta-11/MIP-3 beta/ELC/Exodus 3 mediates tumor rejection of murine breast cancer cells through NK cells.

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    Braun, S E; Chen, K; Foster, R G; Kim, C H; Hromas, R; Kaplan, M H; Broxmeyer, H E; Cornetta, K

    2000-04-15

    CK beta-11 chemoattracts T cells, B cells, dendritic cells, macrophage progenitors, and NK cells and facilitates dendritic cell and T cell interactions in secondary lymphoid tissues. We hypothesized that expression of CK beta-11 in tumor cells may generate antitumor immunity through these interactions. After transduction with the retroviral vector L(CK beta 11)SN, the murine breast cancer cell line C3L5 (C3L5-CK beta 11) showed expression of retroviral mRNA by Northern analysis and production of functional CK beta-11 by chemotaxis of human NK cells to C3L5-CK beta 11 supernatant. Only 10% of mice injected with C3L5-CK beta 11 developed tumors, compared with 100% of mice injected with a transduced control C3L5 line (C3L5-G1N). Importantly, the in vitro growth characteristics of the CK beta-11-transduced cell line were unaffected, suggesting the difference in growth in vivo was a result of chemokine production. Vaccination with C3L5-CK beta 11 partially protected animals from parental C3L5 challenge. Immunodepletion with anti-asialo-GM1 or anti-CD4 during C3L5-CK beta 11 vaccination significantly reduced CK beta-11 antitumor activity compared with control and anti-CD8-treated groups. Splenocytes from NK-depleted animals transferred the acquired immunity generated with C3L5-CK beta 11 vaccination, while splenocytes from the CD4-depleted animals did not. These results indicate, for the first time, that expression of CK beta-11 in a breast cancer cell line mediates rejection of the transduced tumor through a mechanism involving NK and CD4+ cells. Furthermore, CK beta-11-transduced tumor cells generate long-term antitumor immunity that requires CD4+ cells. These studies demonstrate the potential role of CK beta-11 as an adjuvant in stimulating antitumor responses.

  17. Decreased Cortisol and Pain in Breast Cancer: Biofield Therapy Potential.

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    Running, Alice

    2015-01-01

    Breast cancer is one of the leading causes of cancer death among women of all races. Pain is a common symptom associated with cancer; 75-90% of cancer patients experience pain during their illness and up to 50% of that pain is undertreated. Unrelieved pain leads to increased levels of the stress hormone cortisol. The purpose of this study was to examine the impact of bioenergy on fecal cortisol levels for mice injected with murine mammary carcinoma 4T1 in two separate pilot studies. Using a multiple experimental group design, six to eight week old female BALB/c mice were injected with tumor and randomly assigned, in groups of 10, to daily treatment, every other day treatment, and no treatment groups. Five days after tumor cell injection, bioenergy interventions were begun for a period of ten consecutive days. Fecal samples were collected for each study and ELISA analysis was conducted at the end of both studies. For both studies, cortisol levels were decreased in the every other day treatment groups but remained high in the no treatment groups. Future studies utilizing bioenergy therapies on cortisol levels in a murine breast cancer model can begin to describe pain outcomes and therapeutic dose.

  18. Decreased Cortisol and Pain in Breast Cancer: Biofield Therapy Potential

    Directory of Open Access Journals (Sweden)

    Alice Running

    2015-01-01

    Full Text Available Breast cancer is one of the leading causes of cancer death among women of all races. Pain is a common symptom associated with cancer; 75–90% of cancer patients experience pain during their illness and up to 50% of that pain is undertreated. Unrelieved pain leads to increased levels of the stress hormone cortisol. The purpose of this study was to examine the impact of bioenergy on fecal cortisol levels for mice injected with murine mammary carcinoma 4T1 in two separate pilot studies. Using a multiple experimental group design, six to eight week old female BALB/c mice were injected with tumor and randomly assigned, in groups of 10, to daily treatment, every other day treatment, and no treatment groups. Five days after tumor cell injection, bioenergy interventions were begun for a period of ten consecutive days. Fecal samples were collected for each study and ELISA analysis was conducted at the end of both studies. For both studies, cortisol levels were decreased in the every other day treatment groups but remained high in the no treatment groups. Future studies utilizing bioenergy therapies on cortisol levels in a murine breast cancer model can begin to describe pain outcomes and therapeutic dose.

  19. The efficacy of nuclease-resistant Chol-siRNA in primary breast tumors following complexation with PLL-PEG(5K).

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    Ambardekar, Vishakha V; Wakaskar, Rajesh R; Sharma, Bhawna; Bowman, Joy; Vayaboury, Willy; Singh, Rakesh K; Vetro, Joseph A

    2013-07-01

    Modifying the sense strand of nuclease-resistant siRNA with 3'-cholesterol (Chol-*siRNA) increases mRNA suppression after i.v. administration but with relatively low efficacy. We previously found evidence in vitro that suggests complexation of Chol-siRNA with PLL-PEG(5K), a block copolymer of poly-l-lysine and 5 kDa polyethylene glycol, may increase the efficacy of Chol-siRNA in vivo in a PLL block length-dependent manner. In this study, the extent that polyplexes of PLL10-PEG(5K), PLL30-PEG(5K), and PLL50-PEG(5K) protect complexed Chol-siRNA in high concentrations of murine serum and affect the activity of Chol-*siRNA in murine 4T1 breast tumor epithelial cells in vitro and in primary orthotopic tumors of 4T1 was compared. PLL-PEG(5K) required 3'-Chol to protect full-length siRNA from nuclease degradation in 90% (v/v) murine serum and protection was increased by increasing PLL block length and nuclease resistance of Chol-siRNA. Polyplexes of Chol-*siLuc suppressed stably expressed luciferase in 4T1-Luc cells to different levels in vitro where PLL30 > PLL50 > PLL10. In contrast, only polyplexes of Chol-*siLuc and PLL30-PEG(5K) or PLL50-PEG(5K) suppressed high levels of luciferase in primary orthotopic tumors of 4T1-Luc after i.v. administration, whereas polyplexes of Chol-*siLuc and PLL10-PEG(5K), inactive Chol-*siCtrl polyplexes of PLL-PEG(5K), or Chol-*siLuc alone had no detectable activity. As a whole, these results indicate that polyplexes of PLL-PEG(5K) increase the efficacy of nuclease-resistant Chol-siRNA in primary breast tumors after i.v. administration in a PLL block length-dependent manner. Thus, complexation of Chol-siRNA with PLL-PEG(5K) may be a promising approach to increase the efficacy of Chol-siRNA in a wide range of primary tumors, metastases, and other tissues but likely requires a PLL block length that balances polymer-related adverse effects, Chol-siRNA bioavailability, and subsequent activity in the target cell. Copyright © 2013 Elsevier Ltd

  20. Relating Doses of Contrast Agent Administered to TIC and Semi-Quantitative Parameters on DCE-MRI: Based on a Murine Breast Tumor Model.

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    Menglin Wu

    Full Text Available To explore the changes in the time-signal intensity curve(TIC type and semi-quantitative parameters of dynamic contrast-enhanced(DCEimaging in relation to variations in the contrast agent(CA dosage in the Walker 256 murine breast tumor model, and to determine the appropriate parameters for the evaluation ofneoadjuvantchemotherapy(NACresponse.Walker 256 breast tumor models were established in 21 rats, which were randomly divided into three groups of7rats each. Routine scanning and DCE-magnetic resonance imaging (MRI of the rats were performed using a 7T MR scanner. The three groups of rats were administered different dosages of the CA0.2mmol/kg, 0.3mmol/kg, and 0.5mmol/kg, respectively; and the corresponding TICs the semi-quantitative parameters were calculated and compared among the three groups.The TICs were not influenced by the CA dosage and presented a washout pattern in all of the tumors evaluated and weren't influenced by the CA dose. The values of the initial enhancement percentage(Efirst, initial enhancement velocity(Vfirst, maximum signal(Smax, maximum enhancement percentage(Emax, washout percentage(Ewash, and signal enhancement ratio(SER showed statistically significant differences among the three groups (F = 16.952, p = 0.001; F = 69.483, p<0.001; F = 54.838, p<0.001; F = 12.510, p = 0.003; F = 5.248, p = 0.031; F = 9.733, p = 0.006, respectively. However, the values of the time to peak(Tpeak, maximum enhancement velocity(Vmax, and washout velocity(Vwashdid not differ significantly among the three dosage groups (F = 0.065, p = 0.937; F = 1.505, p = 0.273; χ2 = 1.423, p = 0.319, respectively; the washout slope(Slopewash, too, was uninfluenced by the dosage(F = 1.654, p = 0.244.The CA dosage didn't affect the TIC type, Tpeak, Vmax, Vwash or Slopewash. These dose-independent parameters as well as the TIC type might be more useful for monitoring the NAC response because they allow the comparisons of the DCE data obtained using different

  1. Quantifying shape changes of silicone breast implants in a murine model using in vivo micro-CT.

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    Anderson, Emily E; Perilli, Egon; Carati, Colin J; Reynolds, Karen J

    2017-08-01

    A major complication of silicone breast implants is the formation of a capsule around the implant known as capsular contracture which results in the distortion of the implant. Recently, a mouse model for studying capsular contracture was examined using micro-computed tomography (micro-CT), however, only qualitative changes were reported. The aim of this study was to develop a quantitative method for comparing the shape changes of silicone implants using in vivo micro-CT. Mice were bilaterally implanted with silicone implants and underwent ionizing radiation to induce capsular contracture. On day 28 post-surgery mice were examined in vivo using micro-CT. The reconstructed cross-section images were visually inspected to identify distortion. Measurements were taken in 2D and 3D to quantify the shape of the implants in the normal (n = 11) and distorted (n = 5) groups. The degree of anisotropy was significantly higher in the distorted implants in the transaxial view (0.99 vs. 1.19, p = 0.002) and the y-axis lengths were significantly shorter in the sagittal (9.27 mm vs. 8.55 mm, p = 0.015) and coronal (9.24 mm vs. 8.76 mm, p = 0.031) views, indicating a deviation from the circular cross-section and shortening of the long axis. The 3D analysis revealed a significantly lower average thickness (sphere-fitting method) in distorted implants (6.86 mm vs. 5.49 mm, p = 0.002), whereas the volume and surface area did not show significant changes. Statistically significant differences between normal and distorted implants were found in 2D and 3D using distance measurements performed via micro-CT. This objective analysis method can be useful for a range of studies involving deformable implants using in vivo micro-CT. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1447-1452, 2017. © 2016 Wiley Periodicals, Inc.

  2. Inflammatory peroxidases promote breast cancer progression in mice via regulation of the tumour microenvironment.

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    Panagopoulos, Vasilios; Leach, Damien A; Zinonos, Irene; Ponomarev, Vladimir; Licari, Giovanni; Liapis, Vasilios; Ingman, Wendy V; Anderson, Peter; DeNichilo, Mark O; Evdokiou, Andreas

    2017-04-01

    Myeloperoxidase (MPO) and eosinophil peroxidase (EPO) are heme-containing enzymes, well known for their antimicrobial activity, are released in high quantities by infiltrating immune cells in breast cancer. However, the functional importance of their presence within the tumour microenvironment is unclear. We have recently described a new role for peroxidases as key regulators of fibroblast and endothelial cell functionality. In the present study, we investigate for the first time, the ability of peroxidases to promote breast cancer development and progression. Using the 4T1 syngeneic murine orthotopic breast cancer model, we examined whether increased levels of peroxidases in developing mammary tumours influences primary tumour growth and metastasis. We showed that MPO and EPO stimulation increased mammary tumour growth and enhanced lung metastases, effects that were associated with reduced tumour necrosis, increased collagen deposition and neo-vascularisation within the primary tumour. In vitro, peroxidase treatment, robustly stimulated human mammary fibroblast migration and collagen type I and type VI secretion. Mechanistically, peroxidases induced the transcription of pro-tumorigenic and metastatic MMP1, MMP3 and COX-2 genes. Taken together, these findings identify peroxidases as key contributors to cancer progression by augmenting pro-tumorigenic collagen production and angiogenesis. Importantly, this identifies inflammatory peroxidases as therapeutic targets in breast cancer therapy.

  3. Sulindac, a non-steroidal anti-inflammatory drug, mediates breast cancer inhibition as an immune modulator.

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    Yin, Tao; Wang, Guoping; Ye, Tinghong; Wang, Yongsheng

    2016-01-18

    The cooperation of adaptive immunity with pharmacologic therapy influences cancer progression. Though non-steroidal anti-inflammatory drugs (NSAIDs) have a long history of cancer prevention, it is unclear whether adaptive immune system affects the action of those drugs. In present study, we revealed a novel immunological mechanism of sulindac. Our data showed that sulindac had substantial efficacy as a single agent against 4T1 murine breast cancer and prolonged the survival of tumor-bearing mice. However, in the athymic nude mice, sulindac treatment was ineffective. Further in vivo T cell subsets depletion experiments showed that CD8+ T lymphocytes deficiency reversed the anti-tumor effect of sulindac. In addition, sulindac significantly reduced M2 macrophages recruitment, cancer-related inflammation and tumor angiogenesis. Our results advance our understanding of the mechanisms of NSAIDs, and more importantly, this will provide insight into rational drug design or antitumor immunotherapy.

  4. Pre-osteoblastic MC3T3-E1 promote breast cancer cell growth in bone in a murine xenograft model

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    The bones are the most common sites of breast cancer metastasis. Upon arrival within the bone microenvironment, breast cancer cells coordinate the activities of stromal cells, resulting in an increase in osteoclast activity and bone matrix degradation. In late stages of bone metastasis, breast cance...

  5. Cloning of linear T-cell epitops of EG95 antigen of Echinococcus granulosus into pGEX4t1 vector and expression analysis by SDS-PAGE

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    Roghayeh Mesri

    2016-12-01

    Full Text Available Background & Objectives: Echinococcus granulosus causes a common disease between humans and animals that called hydatid cyst or hydatidosis. The recombinant EG95 vaccine based on cloning of the 25 KD oncospheral antigen-Eg95- in pGEX stimulated significant humoral and cellular immunity in sheep, but regarding the effect of TH1cell immunity against this parasite and the influence of the linear T-cell epitopes in stimulating this immunity, only the coding sequence of linear T Cell epitopes of EG95 was cloned in pGEX and analyzed it's expression to optimize the qualification of this available vaccine in this study. Materials & Methods: The coding sequence of EG95 linear epitopes by IEDB software were predicted and synthesized. After PCR, the amplicon and pGEX4T1 were digested by xhoI restriction enzyme, the fragment was cloned into pGEX4T1 by heat shock method, and Positive colonies were selected by direct PCR with specific primers. The recombinant protein expression was evaluated in BL21 cells by 10% SDS-PAGE. Results: The coding sequence of EG95 linear T-cell epitopes was amplified by PCR and cloned into pGEX4T1 vector.  The recombinant plasmid was selected with Colony PCR and size difference between intact and recombinant purificated vectors. Recombinant protein expression with high significant concentration was recognized by SDS-PAGE. Conclusion: The EG95 linear T-cell epitopes coding sequence has been successfully cloned into pGEX4T1 vector and expressed into BL21 cells.

  6. The ruthenium complex cis-(dichloro)tetraammineruthenium(III) chloride presents selective cytotoxicity against murine B cell lymphoma (A-20), murine ascitic sarcoma 180 (S-180), human breast adenocarcinoma (SK-BR-3), and human T cell leukemia (Jurkat) tumor cell lines.

    Science.gov (United States)

    Silveira-Lacerda, Elisângela de Paula; Vilanova-Costa, Cesar Augusto Sam Tiago; Hamaguchi, Amélia; Pavanin, Luiz Alfredo; Goulart, Luiz Ricardo; Homsi-Brandenburgo, Maria Inês; Dos Santos, Wagner Batista; Soares, Andreimar Martins; Nomizo, Auro

    2010-06-01

    The aim of present study was to verify the in vitro antitumor activity of a ruthenium complex, cis-(dichloro)tetraammineruthenium(III) chloride (cis-[RuCl(2)(NH(3))(4)]Cl) toward different tumor cell lines. The antitumor studies showed that ruthenium(III) complex presents a relevant cytotoxic activity against murine B cell lymphoma (A-20), murine ascitic sarcoma 180 (S-180), human breast adenocarcinoma (SK-BR-3), and human T cell leukemia (Jurkat) cell lines and a very low cytotoxicity toward human peripheral blood mononuclear cells. The ruthenium(III) complex decreased the fraction of tumor cells in G0/G1 and/or G2-M phases, indicating that this compound may act on resting/early entering G0/G1 cells and/or precycling G2-M cells. The cytotoxic activity of a high concentration (2 mg mL(-1)) of cis-[RuCl(2)(NH(3))(4)]Cl toward Jurkat cells correlated with an increased number of annexin V-positive cells and also the presence of DNA fragmentation, suggesting that this compound induces apoptosis in tumor cells. The development of new antineoplastic medications demands adequate knowledge in order to avoid inefficient or toxic treatments. Thus, a mechanistic understanding of how metal complexes achieve their activities is crucial to their clinical success and to the rational design of new compounds with improved potency.

  7. Targeting monocyte chemotactic protein-1 synthesis with bindarit induces tumor regression in prostate and breast cancer animal models.

    Science.gov (United States)

    Zollo, Massimo; Di Dato, Valeria; Spano, Daniela; De Martino, Daniela; Liguori, Lucia; Marino, Natascia; Vastolo, Viviana; Navas, Luigi; Garrone, Beatrice; Mangano, Giorgina; Biondi, Giuseppe; Guglielmotti, Angelo

    2012-08-01

    Prostate and breast cancer are major causes of death worldwide, mainly due to patient relapse upon disease recurrence through formation of metastases. Chemokines are small proteins with crucial roles in the immune system, and their regulation is finely tuned in early inflammatory responses. They are key molecules during inflammatory processes, and many studies are focusing on their regulatory functions in tumor growth and angiogenesis during metastatic cell seeding and spreading. Bindarit is an anti-inflammatory indazolic derivative that can inhibit the synthesis of MCP-1/CCL2, with a potential inhibitory function in tumor progression and metastasis formation. We show here that in vitro, bindarit can modulate cancer-cell proliferation and migration, mainly through negative regulation of TGF-β and AKT signaling, and it can impair the NF-κB signaling pathway through enhancing the expression of the NF-κB inhibitor IkB-α. In vivo administration of bindarit results in impaired metastatic disease in prostate cancer xenograft mice (PC-3M-Luc2 cells injected intra-cardially) and impairment of local tumorigenesis in syngeneic Balb/c mice injected under the mammary gland with murine breast cancer cells (4T1-Luc cells). In addition, bindarit treatment significantly decreases the infiltration of tumor-associated macrophages and myeloid-derived suppressor cells in 4T1-Luc primary tumors. Overall, our data indicate that bindarit is a good candidate for new therapies against prostate and breast tumorigenesis, with an action through impairment of inflammatory cell responses during formation of the tumor-stroma niche microenvironment.

  8. Murine Typhus

    Science.gov (United States)

    Dzul-Rosado, Karla R; Zavala Velázquez, Jorge Ernesto; Zavala-Castro, Jorge

    2012-01-01

    Rickettsia typhi: is an intracellular bacteria who causes murine typhus. His importance is reflected in the high frequency founding specific antibodies against Rickettsia typhi in several worldwide seroepidemiological studies, the seroprevalence ranging between 3-36%. Natural reservoirs of R. typhi are rats (some species belonging the Rattus Genus) and fleas (Xenopsylla cheopis) are his vector. This infection is associated with overcrowding, pollution and poor hygiene. Typically presents fever, headache, rash on trunk and extremities, in some cases may occur organ-specific complications, affecting liver, kidney, lung or brain. Initially the disease is very similar to other diseases, is very common to confuse the murine typhus with Dengue fever, therefore, ignorance of the disease is a factor related to complications or non-specific treatments for the resolution of this infection. This paper presents the most relevant information to consider about the rickettsiosis caused by Rickettsia typhi. PMID:24893060

  9. Plant cyclopeptide RA-V kills human breast cancer cells by inducing mitochondria-mediated apoptosis through blocking PDK1–AKT interaction

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    Fang, Xian-Ying; Chen, Wei [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing (China); Fan, Jun-Ting [State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming (China); Song, Ran; Wang, Lu [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing (China); Gu, Yan-Hong [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Zeng, Guang-Zhi [State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming (China); Shen, Yan; Wu, Xue-Feng [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing (China); Tan, Ning-Hua, E-mail: nhtan@mail.kib.ac.cn [State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming (China); Xu, Qiang, E-mail: molpharm@163.com [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing (China); Sun, Yang, E-mail: yangsun@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing (China)

    2013-02-15

    In the present paper, we examined the effects of a natural cyclopeptide RA-V on human breast cancer cells and the underlying mechanisms. RA-V significantly inhibited the growth of human breast cancer MCF-7, MDA-MB-231 cells and murine breast cancer 4T1 cells. In addition, RA-V triggered mitochondrial apoptotic pathway which was indicated by the loss of mitochondrial membrane potential, the release of cytochrome c, and the activation of caspase cascade. Further study showed that RA-V dramatically inhibited phosphorylation of AKT and 3-phosphoinositide dependent protein kinase 1 (PDK1) in MCF-7 cells. Moreover, RA-V disrupted the interaction between PDK1 and AKT in MCF-7 cells. Furthermore, RA-V-induced apoptosis could be enhanced by phosphatidylinositol 3-kinase inhibitor or attenuated by over-expression of AKT in all the three kinds of breast cancer cells. Taken together, this study shows that RA-V, which can induce mitochondria-mediated apoptosis, exerts strong anti-tumor activity against human breast cancer. The underlying anti-cancer mechanism of RA-V is related to the blockage of the interaction between PDK1 and AKT. - Highlights: ► Plant cyclopeptide RA-V kills human breast cancer cells. ► RA-V triggered mitochondrial apoptotic pathway in human breast cancer cells. ► RA-V inhibited phosphorylation of AKT and PDK1 in breast cancer MCF-7 cells. ► Its mechanism is related to the blockage of the interaction between PDK1 and AKT.

  10. Umbelliprenin is Potentially Toxic Against the HT29, CT26, MCF-7, 4T1, A172, and GL26 Cell Lines, Potentially Harmful Against Bone Marrow-Derived Stem Cells, and Non-Toxic Against Peripheral Blood Mononuclear Cells

    Science.gov (United States)

    Rashidi, Mohsen; Ziai, Seyed Ali; Moini Zanjani, Taraneh; Khalilnezhad, Ahad; Jamshidi, Hamidreza; Amani, Davar

    2016-01-01

    Background Resistance to chemotherapy is a growing concern, thus natural anticancer agents are drawing the attention of many scientists and clinicians. One natural anticancer agent, umbelliprenin, is a coumarin produced by many species of Ferula. Objectives We aimed to examine the inhibitory effect of umbelliprenin on human and mouse bone marrow-derived stem cells (BMDSCs), peripheral blood mononuclear cells (PBMCs), and different cancer cell lines. Materials and Methods In this in vitro experimental study, the HT29, CT26, MCF-7, 4T1, A172, and GL26 cancer cells and human and mouse BMDSCs and PBMCs were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS), incubated at 37°C for 24 hours in a 5% CO2 atmosphere, and then were treated with different concentrations of umbelliprenin dissolved in dimethyl sulfoxide (DMSO) (3, 6, 12, 25, 50, 100, and 200 µg/mL) for 24, 48, and 72 hours at 37°C. Each experiment was performed in triplicate. Finally, the cell survival rate was assessed by MTT assay. The IC50 values were calculated based on the log values using GraphPad Prism version 5 software for windows (La Jolla CA, USA) and were expressed as mean ± SEM. Results Umbelliprenin inhibited the cancer cells in a concentration-dependent (P 0.05). The most sensitive and resistant cell lines at the 24-hour incubation time were 4T1 (IC50, 30.9 ± 3.1 µg/mL) and A172 (IC50, 51.9 ± 6.7 µg/mL); at the 48-hour incubation time: 4T1 (IC50, 30.6 ± 2.6 µg/mL) and CT26 (IC50, 53.2 ± 3.6 µg/mL); and at the 72-hour incubation time: HT29 (IC50, 37.1 ± 1.4 µg/mL) and 4T1 (IC50, 62.2 ± 4.8 µg/mL). Both human and mouse BMDSCs showed the highest resistance at the 24-hour incubation time (IC50s, 254.7 ± 21 and 204.4 ± 4.5 µg/mL, respectively) and the highest sensitivity at the 72-hour incubation time (IC50s, 120.4 ± 5 and 159.0 ± 7.3 µg/mL, respectively). The PBMCs of both human and mouse origin revealed very strong resistance to the studied

  11. Understanding Heterogeneity and Permeability of Brain Metastases in Murine Models of HER2-Positive Breast Cancer Through Magnetic Resonance Imaging: Implications for Detection and Therapy

    Directory of Open Access Journals (Sweden)

    Donna H. Murrell

    2015-06-01

    Full Text Available OBJECTIVES: Brain metastases due to breast cancer are increasing, and the prognosis is poor. Lack of effective therapy is attributed to heterogeneity of breast cancers and their resulting metastases, as well as impermeability of the blood–brain barrier (BBB, which hinders delivery of therapeutics to the brain. This work investigates three experimental models of HER2+ breast cancer brain metastasis to better understand the inherent heterogeneity of the disease. We use magnetic resonance imaging (MRI to quantify brain metastatic growth and explore its relationship with BBB permeability. DESIGN: Brain metastases due to breast cancer cells (SUM190-BR3, JIMT-1-BR3, or MDA-MB-231-BR-HER2 were imaged at 3 T using balanced steady-state free precession and contrast-enhanced T1-weighted spin echo sequences. The histology and immunohistochemistry corresponding to MRI were also analyzed. RESULTS: There were differences in metastatic tumor appearance by MRI, histology, and immunohistochemistry (Ki67, CD31, CD105 across the three models. The mean volume of an MDA-MB-231-BR-HER2 tumor was significantly larger compared to other models (F2,12 = 5.845, P < .05; interestingly, this model also had a significantly higher proportion of Gd-impermeable tumors (F2,12 = 22.18, P < .0001. Ki67 staining indicated that Gd-impermeable tumors had significantly more proliferative nuclei compared to Gd-permeable tumors (t[24] = 2.389, P < .05 in the MDA-MB-231-BR-HER2 model. CD31 and CD105 staining suggested no difference in new vasculature patterns between permeable and impermeable tumors in any model. CONCLUSION: Significant heterogeneity is present in these models of brain metastases from HER2+ breast cancer. Understanding this heterogeneity, especially as it relates to BBB permeability, is important for improvement in brain metastasis detection and treatment delivery.

  12. The antioxidant N-acetylcysteine prevents HIF-1 stabilization under hypoxia in vitro but does not affect tumorigenesis in multiple breast cancer models in vivo.

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    Jaclyn Sceneay

    Full Text Available Intratumoral hypoxia is a poor prognostic factor associated with reduced disease-free survival in many cancer types, including breast cancer. Hypoxia encourages tumor cell proliferation, stimulates angiogenesis and lymphangiogenesis, and promotes epithelial-mesenchymal transition and metastasis. Tumor cells respond to a hypoxic state by stabilizing the Hif-1α subunit of the Hypoxia-Inducible Factor (HIF transcription factor to promote expression of various tumor- and metastasis-promoting hypoxic response genes. The antioxidant N-acetylcysteine (NAC was recently shown to prevent Hif-1α stabilization under hypoxia, and has been identified as a potential alternative method to target the hypoxic response in tumors. We utilized three orthotopic syngeneic murine models of breast cancer, the PyMT, EO771 and 4T1.2 models, to investigate the ability of NAC to modulate the hypoxic response in vitro and in vivo. While NAC prevented Hif-1α stabilization under hypoxia in vitro and increased levels of glutathione in the blood of mice in vivo, this did not translate to a difference in tumor growth or the hypoxic state of the tumor compared to untreated control mice. In addition, NAC treatment actually increased metastatic burden in an experimental metastasis model. This work raises questions regarding the validity of NAC as an anti-tumorigenic agent in breast cancer, and highlights the need to further investigate its properties in vivo in different cancer models.

  13. Differential expression and function of breast regression protein 39 (BRP-39 in murine models of subacute cigarette smoke exposure and allergic airway inflammation

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    Coyle Anthony J

    2011-04-01

    Full Text Available Abstract Background While the presence of the chitinase-like molecule YKL40 has been reported in COPD and asthma, its relevance to inflammatory processes elicited by cigarette smoke and common environmental allergens, such as house dust mite (HDM, is not well understood. The objective of the current study was to assess expression and function of BRP-39, the murine equivalent of YKL40 in a murine model of cigarette smoke-induced inflammation and contrast expression and function to a model of HDM-induced allergic airway inflammation. Methods CD1, C57BL/6, and BALB/c mice were room air- or cigarette smoke-exposed for 4 days in a whole-body exposure system. In separate experiments, BALB/c mice were challenged with HDM extract once a day for 10 days. BRP-39 was assessed by ELISA and immunohistochemistry. IL-13, IL-1R1, IL-18, and BRP-39 knock out (KO mice were utilized to assess the mechanism and relevance of BRP-39 in cigarette smoke- and HDM-induced airway inflammation. Results Cigarette smoke exposure elicited a robust induction of BRP-39 but not the catalytically active chitinase, AMCase, in lung epithelial cells and alveolar macrophages of all mouse strains tested. Both BRP-39 and AMCase were increased in lung tissue after HDM exposure. Examining smoke-exposed IL-1R1, IL-18, and IL-13 deficient mice, BRP-39 induction was found to be IL-1 and not IL-18 or IL-13 dependent, while induction of BRP-39 by HDM was independent of IL-1 and IL-13. Despite the importance of BRP-39 in cellular inflammation in HDM-induced airway inflammation, BRP-39 was found to be redundant for cigarette smoke-induced airway inflammation and the adjuvant properties of cigarette smoke. Conclusions These data highlight the contrast between the importance of BRP-39 in HDM- and cigarette smoke-induced inflammation. While functionally important in HDM-induced inflammation, BRP-39 is a biomarker of cigarette smoke induced inflammation which is the byproduct of an IL-1

  14. A comparative small-animal PET evaluation of [{sup 11}C]tariquidar, [{sup 11}C]elacridar and (R)-[{sup 11}C]verapamil for detection of P-glycoprotein-expressing murine breast cancer

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    Wanek, Thomas; Kuntner, Claudia; Sauberer, Michael [AIT Austrian Institute of Technology GmbH, Health and Environment Department, Molecular Medicine, Seibersdorf (Austria); Bankstahl, Jens P.; Bankstahl, Marion; Loescher, Wolfgang [University of Veterinary Medicine Hannover, Department of Pharmacology, Toxicology and Pharmacy, Hannover (Germany); Stanek, Johann; Langer, Oliver [AIT Austrian Institute of Technology GmbH, Health and Environment Department, Molecular Medicine, Seibersdorf (Austria); Medical University of Vienna, Department of Clinical Pharmacology, Vienna (Austria); Mairinger, Severin [AIT Austrian Institute of Technology GmbH, Health and Environment Department, Molecular Medicine, Seibersdorf (Austria); Medical University of Vienna, Department of Clinical Pharmacology, Vienna (Austria); University of Vienna, Department of Medicinal Chemistry, Vienna (Austria); Strommer, Sabine; Wacheck, Volker; Mueller, Markus [Medical University of Vienna, Department of Clinical Pharmacology, Vienna (Austria); Erker, Thomas [University of Vienna, Department of Medicinal Chemistry, Vienna (Austria)

    2012-01-15

    One important mechanism for chemoresistance of tumours is overexpression of the adenosine triphosphate-binding cassette transporter P-glycoprotein (Pgp). Pgp reduces intracellular concentrations of chemotherapeutic drugs. The aim of this study was to compare the suitability of the radiolabelled Pgp inhibitors [{sup 11}C]tariquidar and [{sup 11}C]elacridar with the Pgp substrate radiotracer (R)-[{sup 11}C]verapamil for discriminating tumours expressing low and high levels of Pgp using small-animal PET imaging in a murine breast cancer model. Murine mammary carcinoma cells (EMT6) were continuously exposed to doxorubicin to generate a Pgp-overexpressing, doxorubicin-resistant cell line (EMT6AR1.0 cells). Both cell lines were subcutaneously injected into female athymic nude mice. One week after implantation, animals underwent PET scans with [{sup 11}C]tariquidar (n = 7), [{sup 11}C]elacridar (n = 6) and (R)-[{sup 11}C]verapamil (n = 7), before and after administration of unlabelled tariquidar (15 mg/kg). Pgp expression in tumour grafts was evaluated by Western blotting. [{sup 11}C]Tariquidar showed significantly higher retention in Pgp-overexpressing EMT6AR1.0 compared with EMT6 tumours: the mean {+-} SD areas under the time-activity curves in scan 1 from time 0 to 60 min (AUC{sub 0-60}) were 38.8 {+-} 2.2 min and 25.0 {+-} 5.3 min (p = 0.016, Wilcoxon matched pairs test). [{sup 11}C]Elacridar and (R)-[{sup 11}C]verapamil were not able to discriminate Pgp expression in tumour models. Following administration of unlabelled tariquidar, both EMT6Ar1.0 and EMT6 tumours showed increases in uptake of [{sup 11}C]tariquidar, [{sup 11}C]elacridar and (R)-[{sup 11}C]verapamil. Among the tested radiotracers, [{sup 11}C]tariquidar performed best in discriminating tumours expressing high and low levels of Pgp. Therefore [{sup 11}C]tariquidar merits further investigation as a PET tracer to assess Pgp expression levels in solid tumours. (orig.)

  15. Interleukin-13 receptor α2 DNA prime boost vaccine induces tumor immunity in murine tumor models

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    Puri Raj K

    2010-11-01

    Full Text Available Abstract Background DNA vaccines represent an attractive approach for cancer treatment by inducing active T cell and B cell immune responses to tumor antigens. Previous studies have shown that interleukin-13 receptor α2 chain (IL-13Rα2, a tumor-associated antigen is a promising target for cancer immunotherapy as high levels of IL-13Rα2 are expressed on a variety of human tumors. To enhance the effectiveness of DNA vaccine, we used extracellular domain of IL-13Rα2 (ECDα2 as a protein-boost against murine tumor models. Methods We have developed murine models of tumors naturally expressing IL-13Rα2 (MCA304 sarcoma, 4T1 breast carcinoma and D5 melanoma tumors transfected with human IL-13Rα2 in syngeneic mice and examined the antitumor activity of DNA vaccine expressing IL-13Rα2 gene with or without ECDα2 protein mixed with CpG and IFA adjuvants as a boost vaccine. Results Mice receiving IL-13Rα2 DNA vaccine boosted with ECDα2 protein were superior in exhibiting inhibition of tumor growth, compared to mice receiving DNA vaccine alone, in both prophylactic and therapeutic vaccine settings. In addition, prime-boost vaccination significantly prolonged the survival of mice compared to DNA vaccine alone. Furthermore, ECDα2 booster vaccination increased IFN-γ production and CTL activity against tumor expressing IL-13Rα2. The immunohistochemical analysis showed the infiltration of CD4 and CD8 positive T cells and IFN-γ-induced chemokines (CXCL9 and CXCL10 in regressing tumors of immunized mice. Finally, the prime boost strategy was able to reduce immunosuppressive CD4+CD25+Foxp3+ regulatory T cells (Tregs in the spleen and tumor of vaccinated mice. Conclusion These results suggest that immunization with IL-13Rα2 DNA vaccine followed by ECDα2 boost mixed with CpG and IFA adjuvants inhibits tumor growth in T cell dependent manner. Thus our results show an enhancement of efficacy of IL-13Rα2 DNA vaccine with ECDα2 protein boost and offers an

  16. Inhibition of p38-MAPK signaling pathway attenuates breast cancer induced bone pain and disease progression in a murine model of cancer-induced bone pain

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    Vanderah Todd W

    2011-10-01

    Full Text Available Abstract Background Mechanisms driving cancer-induced bone pain are poorly understood. A central factor implicated to be a key player in the process of tumorigenesis, osteoclastogenesis and nociception is p38 MAPK. We determined the role of p38 MAPK in a mouse model of breast cancer induced bone pain in which mixed osteolytic and osteoblastic remodeling occurs. Results In cancer-treated mice, acute as well as chronic inhibition of p38 MAPK with SB203580 blocked flinching and guarding behaviors in a dose-dependent manner whereas no effect on thresholds to tactile stimuli was observed. Radiographic analyses of bones demonstrated that chronic inhibition of p38 MAPK reduced bone loss and incidence of spontaneous fracture in cancer-treated mice. Histological analysis of bones collected from mice treated with the p38 MAPK inhibitor showed complete absence of osteoblastic growth in the intramedullary space as well as significantly reduced tumor burden. Conclusions Blockade of non-evoked pain behaviors but not hypersensitivity suggests differences in the underlying mechanisms of specific components of the pain syndrome and a possibility to individualize aspects of pain management. While it is not known whether the role of p38 MAPK signaling can be expanded to other cancers, the data suggest a need for understanding molecular mechanisms and cellular events that initiate and maintain cancer-induced bone pain for effective management for both ongoing pain as well as breakthrough pain.

  17. Comparison the treatment effects between simultaneous dual frequency and single frequency irradiation of ultrasound in a murine model of breast adenocarcinoma

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    Mahboobeh Alamolhoda

    2010-12-01

    Full Text Available Introduction: Transient cavitations induced by low frequency irradiation of ultrasound can be used to treat tumors. Previous studies in in-vitro experiments have shown that induced cavitation by dual or multiple frequencies of ultrasound is greater than induced cavitation by single frequency irradiation. In this study, we compared and evaluated the treatment effects of dual frequency irradiation of ultrasound (1 MHz and 150 kHz and single frequency irradiation in in-vivo experiments on breast adenocarcinoma tumors. Material and Method: In this study, the tumor-bearing mice were divided into 5 groups: control, sham, treated group for 30 min with 150 kHz frequency in continuous mode, another group with 1 MHz frequency in pulse mode, and treated group with combined dual frequency ultrasound (150 kHz in continuous mode and 1 MHz in 80% pulse mode. To evaluate the effects of ultrasound irradiation on tumor growth delay, the volumes of the tumors were investigated for 30 days. Tumor growth delay parameters including relative volume, inhibition ratio percentage and the required times for the tumor volume to reach to two (T2 and five (T5 times its initial volume were calculated. Results: The results showed that the treated groups with single frequency irradiation of 150 kHz continuous mode and 1 MHz pulse mode and combined dual frequency had statistically significant differences in tumor relative volume percentage during the period of 3 to 24 days after treatment (p

  18. Visualisation of sentinel lymph node with indium-based near infrared emitting Quantum Dots in a murine metastatic breast cancer model.

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    Marion Helle

    Full Text Available Due to its non-invasiveness, high temporal resolution and lower cost, fluorescence imaging is an interesting alternative to the current method (blue dye and radiocolloid of sentinel lymph node (SLN mapping in breast cancer. Near-infrared (NIR emitting cadmium-based Quantum Dots (QDs could be used for this purpose; however, their wide application is limited because of the toxicity of heavy metals composing the core. Our recent work demonstrated that indium-based QDs exhibit a weak acute local toxicity in vivo compared to their cadmium-based counterparts. In the present study we confirmed the weak toxicity of CuInS(2/ZnS QDs in different in vitro models. Further in vivo studies in healthy mice showed that In-based QDs could be visualised in SLN in a few minutes after administration with a progressive increase in fluorescence until 8 h. The quantity of indium was assessed in selected organs and tissues by inductively coupled plasma - mass spectroscopy (ICP-MS as a function of post-injection time. QD levels decrease rapidly at the injection point in the first hours after administration with a parallel increase in the lymph nodes and to a lesser extent in the liver and spleen. In addition, we observed that 3.5% of the injected indium dose was excreted in faeces in the first 4 days, with only trace quantities in the urine. Metastatic spread to the lymph nodes may hamper its visualisation. Therefore, we further performed non-invasive fluorescence measurement of QDs in SLN in tumour-bearing mice. Metastatic status was assessed by immunohistology and molecular techniques and revealed the utmost metastatic invasion of 36% of SLN. Fluorescence signal was the same irrespective of SLN status. Thus, near-infrared emitting cadmium-free QDs could be an excellent SLN tracer.

  19. Doxorubicin-mediated bone loss in breast cancer bone metastases is driven by an interplay between oxidative stress and induction of TGFβ.

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    Tapasi Rana

    Full Text Available Breast cancer patients, who are already at increased risk of developing bone metastases and osteolytic bone damage, are often treated with doxorubicin. Unfortunately, doxorubicin has been reported to induce damage to bone. Moreover, we have previously reported that doxorubicin treatment increases circulating levels of TGFβ in murine pre-clinical models. TGFβ has been implicated in promoting osteolytic bone damage, a consequence of increased osteoclast-mediated resorption and suppression of osteoblast differentiation. Therefore, we hypothesized that in a preclinical breast cancer bone metastasis model, administration of doxorubicin would accelerate bone loss in a TGFβ-mediated manner. Administration of doxorubicin to 4T1 tumor-bearing mice produced an eightfold increase in osteolytic lesion areas compared untreated tumor-bearing mice (P = 0.002 and an almost 50% decrease in trabecular bone volume expressed in BV/TV (P = 0.0005, both of which were rescued by anti-TGFβ antibody (1D11. Doxorubicin, which is a known inducer of oxidative stress, decreased osteoblast survival and differentiation, which was rescued by N-acetyl cysteine (NAC. Furthermore, doxorubicin treatment decreased Cu-ZnSOD (SOD1 expression and enzyme activity in vitro, and treatment with anti-TGFβ antibody was able to rescue both. In conclusion, a combination therapy using doxorubicin and anti-TGFβ antibody might be beneficial for preventing therapy-related bone loss in cancer patients.

  20. Doxorubicin-Mediated Bone Loss in Breast Cancer Bone Metastases Is Driven by an Interplay between Oxidative Stress and Induction of TGFβ

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    Rana, Tapasi; Chakrabarti, Anwesa; Freeman, Michael; Biswas, Swati

    2013-01-01

    Breast cancer patients, who are already at increased risk of developing bone metastases and osteolytic bone damage, are often treated with doxorubicin. Unfortunately, doxorubicin has been reported to induce damage to bone. Moreover, we have previously reported that doxorubicin treatment increases circulating levels of TGFβ in murine pre-clinical models. TGFβ has been implicated in promoting osteolytic bone damage, a consequence of increased osteoclast-mediated resorption and suppression of osteoblast differentiation. Therefore, we hypothesized that in a preclinical breast cancer bone metastasis model, administration of doxorubicin would accelerate bone loss in a TGFβ-mediated manner. Administration of doxorubicin to 4T1 tumor-bearing mice produced an eightfold increase in osteolytic lesion areas compared untreated tumor-bearing mice (P = 0.002) and an almost 50% decrease in trabecular bone volume expressed in BV/TV (P = 0.0005), both of which were rescued by anti-TGFβ antibody (1D11). Doxorubicin, which is a known inducer of oxidative stress, decreased osteoblast survival and differentiation, which was rescued by N-acetyl cysteine (NAC). Furthermore, doxorubicin treatment decreased Cu-ZnSOD (SOD1) expression and enzyme activity in vitro, and treatment with anti-TGFβ antibody was able to rescue both. In conclusion, a combination therapy using doxorubicin and anti-TGFβ antibody might be beneficial for preventing therapy-related bone loss in cancer patients. PMID:24205081

  1. Metabolic Plasticity of Metastatic Breast Cancer Cells: Adaptation to Changes in the Microenvironment

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    Rui V. Simões

    2015-08-01

    Full Text Available Cancer cells adapt their metabolism during tumorigenesis. We studied two isogenic breast cancer cells lines (highly metastatic 4T1; nonmetastatic 67NR to identify differences in their glucose and glutamine metabolism in response to metabolic and environmental stress. Dynamic magnetic resonance spectroscopy of 13C-isotopomers showed that 4T1 cells have higher glycolytic and tricarboxylic acid (TCA cycle flux than 67NR cells and readily switch between glycolysis and oxidative phosphorylation (OXPHOS in response to different extracellular environments. OXPHOS activity increased with metastatic potential in isogenic cell lines derived from the same primary breast cancer: 4T1 > 4T07 and 168FARN (local micrometastasis only > 67NR. We observed a restricted TCA cycle flux at the succinate dehydrogenase step in 67NR cells (but not in 4T1 cells, leading to succinate accumulation and hindering OXPHOS. In the four isogenic cell lines, environmental stresses modulated succinate dehydrogenase subunit A expression according to metastatic potential. Moreover, glucose-derived lactate production was more glutamine dependent in cell lines with higher metastatic potential. These studies show clear differences in TCA cycle metabolism between 4T1 and 67NR breast cancer cells. They indicate that metastases-forming 4T1 cells are more adept at adjusting their metabolism in response to environmental stress than isogenic, nonmetastatic 67NR cells. We suggest that the metabolic plasticity and adaptability are more important to the metastatic breast cancer phenotype than rapid cell proliferation alone, which could 1 provide a new biomarker for early detection of this phenotype, possibly at the time of diagnosis, and 2 lead to new treatment strategies of metastatic breast cancer by targeting mitochondrial metabolism.

  2. Grape seed proanthocyanidins induce apoptosis and inhibit metastasis of highly metastatic breast carcinoma cells.

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    Mantena, Sudheer K; Baliga, Manjeshwar S; Katiyar, Santosh K

    2006-08-01

    The strategies available for the treatment of metastatic breast cancer are limited. Dietary botanicals may have a better protective effect on this disease. We therefore investigated the effects of grape seed proanthocyanidins (GSPs) on a highly metastatic mouse mammary carcinoma cell line. In vitro treatment of breast cancer cells, 4T1, MCF-7 and MDA-MB-468, with GSPs resulted in significant inhibition of cellular proliferation and viability, and induction of apoptosis in 4T1 cells in a time- and dose-dependent manner. Further analysis indicated an alteration in the ratio of Bax/Bcl-2 proteins in favor of apoptosis, and the knockdown of Bax using Bax siRNA transfection of 4T1 cells resulted in blocking of GSPs-induced apoptosis. Induction of apoptosis was associated with the release of cytochrome c, increased expression of Apaf-1 and activation of caspase 3 and poly (ADP-ribose) polymerase. Treatment with the pan-caspase inhibitor (Z-VAD-FMK) resulted in partial but significant inhibition of apoptosis in 4T1 cells suggesting the involvement of both caspase activation-dependent and activation-independent pathways in the apoptosis of 4T1 cells induced by GSPs. The effects of dietary GSPs were then examined using an in vivo model in which 4T1 cells were implanted subcutaneously in Balb/c mice. Dietary GSPs (0.2 and 0.5%, w/w) significantly inhibited the growth of the implanted 4T1 tumor cells and increased the ratio of Bax:Bcl-2 proteins, cytochrome c release, induction of Apaf-1 and activation of caspase 3 in the tumor microenvironment. Notably, the metastasis of tumor cells to the lungs was inhibited significantly and the survival of the mice enhanced. These data suggest that GSPs possess chemotherapeutic efficacy against breast cancer including inhibition of metastasis.

  3. Alginic acid-coated chitosan nanoparticles loaded with legumain DNA vaccine: effect against breast cancer in mice.

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    Ze Liu

    Full Text Available Legumain-based DNA vaccines have potential to protect against breast cancer. However, the lack of a safe and efficient oral delivery system restricts its clinical application. Here, we constructed alginic acid-coated chitosan nanoparticles (A.C.NPs as an oral delivery carrier for a legumain DNA vaccine. First, we tested its characteristic in acidic environments in vitro. DNA agarose electrophoresis data show that A.C.NPs protected DNA better from degradation in acidic solution (pH 1.5 than did chitosan nanoparticles (C.NPs. Furthermore, size distribution analysis showed that A.C.NPs tended to aggregate and form micrometer scale complexes in pH<2.7, while dispersing into nanoparticles with an increase in pH. Mice were intragastrically administrated A.C.NPs carrying EGFP plasmids and EGFP expression was detected in the intestinal Peyer's patches. Full-length legumain plasmids were loaded into different delivery carriers, including C.NPs, attenuated Salmonella typhimurium and A.C.NPs. A.C.NPs loaded with empty plasmids served as a control. Oral vaccination was performed in the murine orthotopic 4T1 breast cancer model. Our data indicate that tumor volume was significantly smaller in groups using A.C.NPs or attenuated Salmonella typhimurium as carriers. Furthermore, splenocytes co-cultured them with 4T1 cells pre-stimulated with CoCl2, which influenced the translocation of legumain from cytoplasm to plasma membrane, showed a 4.7 and 2.3 folds increase in active cytotoxic T lymphocytes (CD3(+/CD8(+/CD25(+ when treated with A.C.NPs carriers compared with PBS C.NPs. Our study suggests that C.NPs coated with alginic acid may be a safe and efficient tool for oral delivery of a DNA vaccine. Moreover, a legumain DNA vaccine delivered orally with A.C.NPs can effectively improve autoimmune response and protect against breast cancer in mice.

  4. Core Needle Biopsy of Breast Cancer Tumors Increases Distant Metastases in a Mouse Model12

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    Mathenge, Edward Gitau; Dean, Cheryl Ann; Clements, Derek; Vaghar-Kashani, Ahmad; Photopoulos, Steffany; Coyle, Krysta Mila; Giacomantonio, Michael; Malueth, Benjamin; Nunokawa, Anna; Jordan, Julie; Lewis, John D.; Gujar, Shashi Ashok; Marcato, Paola; Lee, Patrick W.K.; Giacomantonio, Carman Anthony

    2014-01-01

    INTRODUCTION: Incisional biopsies, including the diagnostic core needle biopsy (CNB), routinely performed before surgical excision of breast cancer tumors are hypothesized to increase the risk of metastatic disease. In this study, we experimentally determined whether CNB of breast cancer tumors results in increased distant metastases and examine important resultant changes in the primary tumor and tumor microenvironment associated with this outcome. METHOD: To evaluate the effect of CNB on metastasis development, we implanted murine mammary 4T1 tumor cells in BALB/c mice and performed CNB on palpable tumors in half the mice. Subsequently, emulating the human scenario, all mice underwent complete tumor excision and were allowed to recover, with attendant metastasis development. Tumor growth, lung metastasis, circulating tumor cell (CTC) levels, variation in gene expression, composition of the tumor microenvironment, and changes in immunologic markers were compared in biopsied and non-biopsied mice. RESULTS: Mice with biopsied tumors developed significantly more lung metastases compared to non-biopsied mice. Tumors from biopsied mice contained a higher frequency of myeloid-derived suppressor cells (MDSCs) accompanied by reduced CD4 + T cells, CD8 + T cells, and macrophages, suggesting biopsy-mediated development of an increasingly immunosuppressive tumor microenvironment. We also observed a CNB-dependent up-regulation in the expression of SOX4, Ezh2, and other key epithelial-mesenchymal transition (EMT) genes, as well as increased CTC levels among the biopsy group. CONCLUSION: CNB creates an immunosuppressive tumor microenvironment, increases EMT, and facilitates release of CTCs, all of which likely contribute to the observed increase in development of distant metastases. PMID:25425969

  5. Minimally toxic approach for treatment of cutaneous breast cancer metastases: capecitabine-enhanced photodynamic therapy

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    Anand, Sanjay; Bullock, Taylor; Maytin, Edward V.

    2017-02-01

    Cutaneous metastasis (CM) occurs in 20% of patients with breast carcinoma (BCA), and is extremely difficult to treat. These CM are relatively resistant to chemotherapy, generally responding only to ionizing radiation (IR). Multiple rounds of IR, however, lead to debilitating fibrosis and radiation dermatitis. An alternative to IR is needed for better management of BCA/CM. In our laboratory, we have developed differentiation-enhanced combination PDT (cPDT), a concept in which a pro-differentiating agent (methotrexate; vitamin D; or 5-fluorouracil, 5FU) is used as a neoadjuvant prior to PDT. After using these neoadjuvants, levels of protoporphyrin IX (PpIX) were elevated in animal tumor models of skin, prostate, and BCA, leading to better PDT efficacy. However, all the agents have toxicity issues. Here, we use a nontoxic 5FU precursor called Capecitabine (CPBN) for cPDT. CBPN is a standard chemotherapeutic for metastatic BCA, and is metabolized to 5FU specifically within tumor tissue. Murine (4T1) and human (MCF-7) BCA cell lines were injected into breast fat pads of nude mice. After tumor nodules appeared, CPBN (400-600 mg/kg/day) was administered by oral gavage for five days followed by intraperitoneal ALA administration on day 6. Mice were sacrificed and tumors harvested. CPBN pretreatment led to a 4-fold elevation of PpIX levels in tumors, relative to vehicle control. Not only did PpIX levels increase, but also PpIX distribution became more homogeneous after CPBN pretreatment. In summary, the use of non-toxic CPBN as a neoadjuvant prior to PDT is a combination approach with significant potential for translation into the clinic.

  6. Aptamer-conjugated Magnetic Nanoparticles as Targeted Magnetic Resonance Imaging Contrast Agent for Breast Cancer

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    Keshtkar, Mohammad; Shahbazi-Gahrouei, Daryoush; Khoshfetrat, Seyyed Mehdi; Mehrgardi, Masoud A.; Aghaei, Mahmoud

    2016-01-01

    Early detection of breast cancer is the most effective way to improve the survival rate in women. Magnetic resonance imaging (MRI) offers high spatial resolution and good anatomic details, and its lower sensitivity can be improved by using targeted molecular imaging. In this study, AS1411 aptamer was conjugated to Fe3O4@Au nanoparticles for specific targeting of mouse mammary carcinoma (4T1) cells that overexpress nucleolin. In vitro cytotoxicity of aptamer-conjugated nanoparticles was assessed on 4T1 and HFFF-PI6 (control) cells. The ability of the synthesized nanoprobe to target specifically the nucleolin overexpressed cells was assessed with the MRI technique. Results show that the synthesized nanoprobe produced strongly darkened T2-weighted magnetic resonance (MR) images with 4T1 cells, whereas the MR images of HFFF-PI6 cells incubated with the nanoprobe are brighter, showing small changes compared to water. The results demonstrate that in a Fe concentration of 45 μg/mL, the nanoprobe reduced by 90% MR image intensity in 4T1 cells compared with the 27% reduction in HFFF-PI6 cells. Analysis of MR signal intensity showed statistically significant signal intensity difference between 4T1 and HFFF-PI6 cells treated with the nanoprobe. MRI experiments demonstrate the high potential of the synthesized nanoprobe as a specific MRI contrast agent for detection of nucleolin-expressing breast cancer cells. PMID:28028501

  7. Effect of Obesity and Chronic Inflammation on TRAIL-Based Immunotherapy for Advanced Breast Cancer

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    2015-04-01

    Results pertaining to Task 1. Altered serum cytokine profile in female BALB/c diet -induced obese (DIO) mice The majority of prior studies on murine DIO...stromal cell composition . As visceral adipose tissue increases in obese mice and obesity triggers increased production of adipokines like IL-6 and...percentages and/or phenotypes of DC in mice with 4T1 tumors in the absence of any therapy. Diet -induced obese mice were generated by feeding cohorts of

  8. Adoptive transfer of ex vivo expanded Vγ9Vδ2 T cells in combination with zoledronic acid inhibits cancer growth and limits osteolysis in a murine model of osteolytic breast cancer.

    Science.gov (United States)

    Zysk, Aneta; DeNichilo, Mark O; Panagopoulos, Vasilios; Zinonos, Irene; Liapis, Vasilios; Hay, Shelley; Ingman, Wendy; Ponomarev, Vladimir; Atkins, Gerald; Findlay, David; Zannettino, Andrew; Evdokiou, Andreas

    2017-02-01

    Bone metastases occur in over 75% of patients with advanced breast cancer and are responsible for high levels of morbidity and mortality. In this study, ex vivo expanded cytotoxic Vγ9Vδ2 T cells isolated from human peripheral blood were tested for their anti-cancer efficacy in combination with zoledronic acid (ZOL), using a mouse model of osteolytic breast cancer. In vitro, expanded Vγ9Vδ2 T cells were cytotoxic against a panel of human breast cancer cell lines, and ZOL pre-treatment further sensitised breast cancer cells to killing by Vγ9Vδ2 T cells. Vγ9Vδ2 T cells adoptively transferred into NOD/SCID mice localised to osteolytic breast cancer lesions in the bone, and multiple infusions of Vγ9Vδ2 T cells reduced tumour growth in the bone. ZOL pre-treatment potentiated the anti-cancer efficacy of Vγ9Vδ2 T cells, with mice showing further reductions in tumour burden. Mice treated with the combination also had reduced tumour burden of secondary pulmonary metastases, and decreased bone degradation. Our data suggests that adoptive transfer of Vγ9Vδ2 T cell in combination with ZOL may prove an effective immunotherapeutic approach for the treatment of breast cancer bone metastases. Copyright © 2016. Published by Elsevier Ireland Ltd.

  9. Breast lift

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    Mastopexy; Breast lift with reduction; Breast lift with augmentation ... enlargement with implants) when they have a breast lift. ... it for medical reasons. Women usually have breast lifts to lift sagging, loose breasts. Pregnancy, breastfeeding, and ...

  10. WNT5A inhibits metastasis and alters splicing of Cd44 in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Wen Jiang

    Full Text Available Wnt5a is a non-canonical signaling Wnt. Low expression of WNT5A is correlated with poor prognosis in breast cancer patients. The highly invasive breast cancer cell lines, MDA-MB-231 and 4T1, express very low levels of WNT5A. To determine if enhanced expression of WNT5A would affect metastatic behavior, we generated WNT5A expressing cells from the 4T1 and MDA-MB-231 parental cell lines. WNT5A expressing cells demonstrated cobblestone morphology and reduced in vitro migration relative to controls. Cell growth was not altered. Metastasis to the lung via tail vein injection was reduced in the 4T1-WNT5A expressing cells relative to 4T1-vector controls. To determine the mechanism of WNT5A action on metastasis, we performed microarray and whole-transcriptome sequence analysis (RNA-seq to compare gene expression in 4T1-WNT5A and 4T1-vector cells. Analysis indicated highly significant alterations in expression of genes associated with cellular movement. Down-regulation of a subset of these genes, Mmp13, Nos2, Il1a, Cxcl2, and Lamb3, in WNT5A expressing cells was verified by semi-quantitative RT-PCR. Significant differences in transcript splicing were also detected in cell movement associated genes including Cd44. Cd44 is an adhesion molecule with a complex genome structure. Variable exon usage is associated with metastatic phenotype. Alternative spicing of Cd44 in WNT5A expressing cells was confirmed using RT-PCR. We conclude that WNT5A inhibits metastasis through down-regulation of multiple cell movement pathways by regulating transcript levels and splicing of key genes like Cd44.

  11. Systemic siRNA Delivery with a Dual pH-Responsive and Tumor-targeted Nanovector for Inhibiting Tumor Growth and Spontaneous Metastasis in Orthotopic Murine Model of Breast Carcinoma

    Science.gov (United States)

    Fan, Bo; Kang, Lin; Chen, Liqing; Sun, Ping; Jin, Mingji; Wang, Qiming; Bae, You Han; Huang, Wei; Gao, Zhonggao

    2017-01-01

    Phenylboronic acid (PBA)-mediated tumor targeting nanovector is an attractive strategy for enhancing siRNA delivery and treatment of metastatic cancers. However, its nonspecific binding with various biological membranes containing cis-diol moieties restricts its potential application by systematic administration. Herein, we constructed a novel pH-activated “sheddable” PEG-coated nanoparticle for effective treatment of primary tumors and metastases, which was based on the conjugation of catechol group modified poly(ethylene glycol) (PEG-Cat) and PBA-terminated polyethylenimine (PEI-PBA) via the borate ester formed between PBA and Cat. By virtue of the pH-dependent stability of borate ester in an aqueous medium, the PEG-shell could “shield” the PBA ligand in systemic circulation to reduce its “off-target effect”, while PEG was detached at tumor extracellular pH (~6.5) to expose intact PBA moiety. Simultaneously, the PBA ligand could bind with overexpressed sialic acid residues on cancer cells, giving rise to enhanced cellular internalization. In addition, the PBA moieties could also couple with each 3'-end ribose of double-stranded siRNA. siRNAs were used as both a payload and a pH-responsive intermolecular cross-linker, and thereby acquired sufficient stability during circulating in blood and a rapidly triggered release in response to acidic endosomal/lysosomal pH-stimuli. As a result, this dual pH-sensitive nanoparticle showed enhanced siRNA uptake, gene silencing efficacy and anti-metastatic effects in vitro. Furthermore, in vivo studies demonstrated that PBA-based nanoparticles effectively accumulated in tumor and inhibited tumor growth and metastasis in 4T1 orthotopic mammary tumor model after intravenous administration. PMID:28042340

  12. Continuous requirement of ErbB2 kinase activity for loss of cell polarity and lumen formation in a novel ErbB2/Neu-driven murine cell line model of metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Cesar F Ortega-Cava

    2011-01-01

    Full Text Available Background: Well over a quarter of human breast cancers are ErbB2-driven and constitute a distinct subtype with substantially poorer prognosis. Yet, there are substantial gaps in our understanding of how ErbB2 tyrosine kinase activity unleashes a coordinated program of cellular and extracellular alterations that culminate in aggressive breast cancers. Cellular models that exhibit ErbB2 kinase dependency and can induce metastatic breast cancer in immune competent hosts are likely to help bridge this gap. Materials and Methods: Here, we derived and characterized a cell line model obtained from a transgenic ErbB2/Neu-driven mouse mammary adenocarcinoma. Results: The MPPS1 cell line produces metastatic breast cancers when implanted in the mammary fat pads of immune-compromised as well as syngeneic immune-competent hosts. MPPS1 cells maintain high ErbB2 overexpression when propagated in DFCI-1 or related media, and their growth is ErbB2-dependent, as demonstrated by concentration-dependent inhibition of proliferation with the ErbB kinase inhibitor Lapatinib. When grown in 3-dimensional (3-D culture on Matrigel, MPPS1 cells predominantly form large irregular cystic and solid structures. Remarkably, low concentrations of Lapatinib led to a switch to regular acinar growth on Matrigel. Immunofluorescence staining of control vs. Lapatinib-treated acini for markers of epithelial polarity revealed that inhibition of ErbB2 signaling led to rapid resumption of normal mammary epithelium-like cell polarity. Conclusions: The strict dependence of the MPPS1 cell system on ErbB2 signals for proliferation and alterations in cell polarity should allow its use to dissect ErbB2 kinase-dependent signaling pathways that promote loss of cell polarity, a key component of the epithelial mesenchymal transition and aggressiveness of ErbB2-driven breast cancers.

  13. Ultrasound - Breast

    Science.gov (United States)

    ... Physician Resources Professions Site Index A-Z Ultrasound - Breast Ultrasound imaging of the breast uses sound waves ... the Breast? What is Ultrasound Imaging of the Breast? Ultrasound is safe and painless, and produces pictures ...

  14. Breast pain

    Science.gov (United States)

    Pain - breast; Mastalgia; Mastodynia; Breast tenderness ... There are many possible causes for breast pain. For example, hormone level changes from menstruation or pregnancy often cause breast tenderness. Some swelling and tenderness just before your period ...

  15. Breast Reconstruction

    Science.gov (United States)

    ... rebuild the shape of the breast. Instead of breast reconstruction, you could choose to wear a breast form ... one woman may not be right for another. Breast reconstruction may be done at the same time as ...

  16. Tumor-induced inflammation in mammary adipose tissue stimulates a vicious cycle of autotaxin expression and breast cancer progression.

    Science.gov (United States)

    Benesch, Matthew G K; Tang, Xiaoyun; Dewald, Jay; Dong, Wei-Feng; Mackey, John R; Hemmings, Denise G; McMullen, Todd P W; Brindley, David N

    2015-09-01

    Compared to normal tissues, many cancer cells overexpress autotaxin (ATX). This secreted enzyme produces extracellular lysophosphatidate, which signals through 6 GPCRs to drive cancer progression. Our previous work showed that ATX inhibition decreases 4T1 breast tumor growth in BALB/c mice by 60% for about 11 d. However, 4T1 cells do not produce significant ATX. Instead, the ATX is produced by adjacent mammary adipose tissue. We investigated the molecular basis of this interaction in human and mouse breast tumors. Inflammatory mediators secreted by breast cancer cells increased ATX production in adipose tissue. The increased lysophosphatidate signaling further increased inflammatory mediator production in adipose tissue and tumors. Blocking ATX activity in mice bearing 4T1 tumors with 10 mg/kg/d ONO-8430506 (a competitive ATX inhibitor, IC90 = 100 nM; Ono Pharma Co., Ltd., Osaka, Japan) broke this vicious inflammatory cycle by decreasing 20 inflammatory mediators by 1.5-8-fold in cancer-inflamed adipose tissue. There was no significant decrease in inflammatory mediator levels in fat pads that did not bear tumors. ONO-8430506 also decreased plasma TNF-α and G-CSF cytokine levels by >70% and leukocyte infiltration in breast tumors and adjacent adipose tissue by >50%. Hence, blocking tumor-driven inflammation by ATX inhibition is effective in decreasing tumor growth in breast cancers where the cancer cells express negligible ATX.

  17. TWIST Represses Estrogen Receptor-alpha Expression by Recruiting the NuRD Protein Complex in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Junjiang Fu, Lianmei Zhang, Tao He, Xiuli Xiao, Xiaoyan Liu, Li Wang, Luquan Yang, Manman Yang, Tiandan Zhang, Rui Chen, Jianming Xu

    2012-01-01

    Full Text Available Loss of estrogen receptor α (ERα expression and gain of TWIST (TWIST1 expression in breast tumors correlate with increased disease recurrence and metastasis and poor disease-free survival. However, the molecular and functional regulatory relationship between TWIST and ERα are unclear. In this study, we found TWIST was associated with a chromatin region in intron 7 of the human ESR1 gene coding for ERα. This association of TWIST efficiently recruited the nucleosome remodeling and deacetylase (NuRD repressor complex to this region, which subsequently decreased histone H3K9 acetylation, increased histone H3K9 methylation and repressed ESR1 expression in breast cancer cells. In agreement with these molecular events, TWIST expression was inversely correlated with ERα expression in both breast cancer cell lines and human breast ductal carcinomas. Forced expression of TWIST in TWIST-negative and ERα-positive breast cancer cells such as T47D and MCF-7 cells reduced ERα expression, while knockdown of TWIST in TWIST-positive and ERα-negative breast cancer cells such as MDA-MB-435 and 4T1 cells increased ERα expression. Furthermore, inhibition of histone deacetylase (HDAC activity including the one in NuRD complex significantly increased ERα expression in MDA-MB-435 and 4T1 cells. HDAC inhibition together with TWIST knockdown did not further increase ERα expression in 4T1 and MDA-MB-435 cells. These results demonstrate that TWIST/NuRD represses ERα expression in breast cancer cells. Therefore, TWIST may serve as a potential molecular target for converting ERα-negative breast cancers to ERα-positive breast cancers, allowing these cancers to restore their sensitivity to endocrine therapy with selective ERα antagonists such as tamoxifen and raloxifene.

  18. Mechanisms driving local breast cancer recurrence in a model of breast-conserving surgery.

    LENUS (Irish Health Repository)

    Smith, Myles J

    2012-02-03

    OBJECTIVE: We aimed to identify mechanisms driving local recurrence in a model of breast-conserving surgery (BCS) for breast cancer. BACKGROUND: Breast cancer recurrence after BCS remains a clinically significant, but poorly understood problem. We have previously reported that recurrent colorectal tumours demonstrate altered growth dynamics, increased metastatic burden and resistance to apoptosis, mediated by upregulation of phosphoinositide-3-kinase\\/Akt (PI3K\\/Akt). We investigated whether similar characteristics were evident in a model of locally recurrent breast cancer. METHODS: Tumours were generated by orthotopic inoculation of 4T1 cells in two groups of female Balb\\/c mice and cytoreductive surgery performed when mean tumour size was above 150 mm(3). Local recurrence was observed and gene expression was examined using Affymetrix GeneChips in primary and recurrent tumours. Differential expression was confirmed with quantitative real-time polymerase chain reaction (qRT-PCR). Phosphorylation of Akt was assessed using Western immunoblotting. An ex vivo heat shock protein (HSP)-loaded dendritic cell vaccine was administered in the perioperative period. RESULTS: We observed a significant difference in the recurrent 4T1 tumour volume and growth rate (p < 0.05). Gene expression studies suggested roles for the PI3K\\/Akt system and local immunosuppression driving the altered growth kinetics. We demonstrated that perioperative vaccination with an ex vivo HSP-loaded dendritic cell vaccine abrogated recurrent tumour growth in vivo (p = 0.003 at day 15). CONCLUSION: Investigating therapies which target tumour survival pathways such as PI3K\\/Akt and boost immune surveillance in the perioperative period may be useful adjuncts to contemporary breast cancer treatment.

  19. Comparative study of two routes of administration of 5-aminolevulinic acid (oral and intratumoral via) and their effect on the accumulation of PpIX in tissues in murine model of breast cancer

    Science.gov (United States)

    González-Agüero, G.; Ramón-Gallegos, E.

    2012-10-01

    Protoporphyrin IX (PpIX) is a photosensitizer synthesized from 5-aminolevulinic acid (ALA) that has been used in photodynamic therapy (PDT) as a promising treatment for many types of cancer. In this work it was quantified the accumulation of PpIX in tumors and in different tissues of female mice (nu/nu) inoculated with breast cancer cells. Two routes of administration of ALA: gastric probe and intratumoral injection were used to find optimum time of accumulation and the via that induce the higher quantity of PpIX to improve the efficiency of PDT. The results show that the accumulation of PpIX using the intratumoral via is two times bigger than the oral via in tumors at 8 h of treatment. The concentrations obtained in the different tissues are not physiologically significant.

  20. Purification of Murine Monoclonal IgM Antibody

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    This paper presents the purification of a monoclonal IgM antibody against human tumor associated antigen Lewis-Y by ion exchange chromatography and gel filtration.Enzyme-linked immunosorbent assay (ELISA) and SDS-polyacrylamide gel electrophoresis (PAGE) were used to identify purified IgM antibody.In flow cytometry analysis, the purified IgM antibody recognizes human breast tumor cell line MCF-7 which expresses Lewis-Y antigen.This work presents a new way for the purification of murine monoclonal IgM antibody.

  1. An autoimmune-mediated strategy for prophylactic breast cancer vaccination.

    Science.gov (United States)

    Jaini, Ritika; Kesaraju, Pavani; Johnson, Justin M; Altuntas, Cengiz Z; Jane-Wit, Daniel; Tuohy, Vincent K

    2010-07-01

    Although vaccination is most effective when used to prevent disease, cancer vaccine development has focused predominantly on providing therapy against established growing tumors. The difficulty in developing prophylactic cancer vaccines is primarily due to the fact that tumor antigens are variations of self proteins and would probably mediate profound autoimmune complications if used in a preventive vaccine setting. Here we use several mouse breast cancer models to define a prototypic strategy for prophylactic cancer vaccination. We selected alpha-lactalbumin as our target vaccine autoantigen because it is a breast-specific differentiation protein expressed in high amounts in the majority of human breast carcinomas and in mammary epithelial cells only during lactation. We found that immunoreactivity against alpha-lactalbumin provides substantial protection and therapy against growth of autochthonous tumors in transgenic mouse models of breast cancer and against 4T1 transplantable breast tumors in BALB/c mice. Because alpha-lactalbumin is conditionally expressed only during lactation, vaccination-induced prophylaxis occurs without any detectable inflammation in normal nonlactating breast tissue. Thus, alpha-lactalbumin vaccination may provide safe and effective protection against the development of breast cancer for women in their post-child-bearing, premenopausal years, when lactation is readily avoidable and risk for developing breast cancer is high.

  2. Genomic profiling of murine mammary tumors identifies potential personalized drug targets for p53-deficient mammary cancers

    Directory of Open Access Journals (Sweden)

    Adam D. Pfefferle

    2016-07-01

    Full Text Available Targeted therapies against basal-like breast tumors, which are typically ‘triple-negative breast cancers (TNBCs’, remain an important unmet clinical need. Somatic TP53 mutations are the most common genetic event in basal-like breast tumors and TNBC. To identify additional drivers and possible drug targets of this subtype, a comparative study between human and murine tumors was performed by utilizing a murine Trp53-null mammary transplant tumor model. We show that two subsets of murine Trp53-null mammary transplant tumors resemble aspects of the human basal-like subtype. DNA-microarray, whole-genome and exome-based sequencing approaches were used to interrogate the secondary genetic aberrations of these tumors, which were then compared to human basal-like tumors to identify conserved somatic genetic features. DNA copy-number variation produced the largest number of conserved candidate personalized drug targets. These candidates were filtered using a DNA-RNA Pearson correlation cut-off and a requirement that the gene was deemed essential in at least 5% of human breast cancer cell lines from an RNA-mediated interference screen database. Five potential personalized drug target genes, which were spontaneously amplified loci in both murine and human basal-like tumors, were identified: Cul4a, Lamp1, Met, Pnpla6 and Tubgcp3. As a proof of concept, inhibition of Met using crizotinib caused Met-amplified murine tumors to initially undergo complete regression. This study identifies Met as a promising drug target in a subset of murine Trp53-null tumors, thus identifying a potential shared driver with a subset of human basal-like breast cancers. Our results also highlight the importance of comparative genomic studies for discovering personalized drug targets and for providing a preclinical model for further investigations of key tumor signaling pathways.

  3. Paget Disease of the Breast

    Science.gov (United States)

    ... Breast Cancer Breast Cancer Patient Breast Cancer Treatment Male Breast Cancer Treatment Breast Cancer Treatment & Pregnancy Breast Cancer Prevention Breast Cancer Screening Health Professional Breast Cancer Treatment Male ... Treatment Breast Cancer Treatment & Pregnancy Breast Cancer Prevention ...

  4. Breast Implants

    Science.gov (United States)

    ... Medical Procedures Implants and Prosthetics Breast Implants Breast Implants Share Tweet Linkedin Pin it More sharing options Linkedin Pin it Email Print Breast implants are medical devices that are implanted under the ...

  5. Fibroadenoma - breast

    Science.gov (United States)

    Breast lump - fibroadenoma; Breast lump - noncancerous; Breast lump - benign ... The cause of fibroadenomas is not known. There may be a connection to a problem with genes. Fibroadenoma is the most common benign ...

  6. What Is Breast Cancer?

    Science.gov (United States)

    ... Research? Breast Cancer About Breast Cancer What Is Breast Cancer? Breast cancer starts when cells in the breast ... spread, see our section on Cancer Basics . Where breast cancer starts Breast cancers can start from different parts ...

  7. OK432优化的内皮细胞疫苗抗小鼠乳腺癌作用研究%Anti-tumor effects of OK432 optimized umbilical vein endothelial cell vaccine in murine breast cancer

    Institute of Scientific and Technical Information of China (English)

    徐茂磊; 周玲; 杨小平

    2014-01-01

    目的:探讨 OK432优化的人脐静脉内皮细胞( HU-VECs)疫苗对小鼠EAC乳腺癌的生长抑制作用。方法体外培养HUVECs,与佐剂OK432混合,制备HUVECs-OK432疫苗,以小鼠 EAC 乳腺癌皮下移植瘤模型考查 HUVECs-OK432疫苗的抗肿瘤效应,并通过ELISA、脾细胞增殖及细胞毒性T淋巴细胞( CTL)杀伤实验检测疫苗免疫后体液及细胞免疫应答水平。结果在预防性免疫中, HUVECs-OK432疫苗可以明显抑制EAC乳腺癌生长;HUVECs-OK432疫苗诱导小鼠产生了高滴度的特异性 HUVEC 抗体;HU-VECs-OK432疫苗能有效刺激免疫小鼠脾淋巴细胞的增殖;HUVECs-OK432组小鼠脾细胞诱导产生了明显的靶向HU-VEC细胞的CTL杀伤作用。结论 HUVECs-OK432疫苗可以有效诱导机体产生靶向HUVEC的特异性体液及细胞免疫应答,从而有效抑制了小鼠EAC乳腺癌的生长。%Aim To investigate the anti-EAC breast cancer effects of viable human umbilical vein endothe-lial cells ( HUVECs) vaccine. Methods Subconflu-ent HUVECs were mixed with OK432 to prepare HU-VECs-OK432 vaccine, and the anti-tumor efficacy of HUVECs-OK432 was investigated using a subcutaneous tumor model of EAC breast cancer. ELISA, splenic lymphocyte proliferation assay and cytotoxic T lympho-cytes ( CTL ) killing assay were adopted to detect the humoral and cellular immune responses after HUVECs-OK432 immunization. Results HUVECs-OK432 im-munization significantly inhibited the growth of EAC tumor in mice in the prophylactic procedures. High ti-ter of anti-HUVEC antibody was elicited by HUVECs-OK432 immunization. The proliferation activity of splenocytes from mice immunized with HUVECs-OK432 was significantly increased. T lymphocytes iso-lated from HUVECs-OK432-immunized mice were dose dependently killing HUVECs in vitro. Conclusion Strong humoral and cellular immune responses targeting HUVEC are elicited by HUVECs-OK432 immuniza-tion, which results in a significant inhibition on the growth

  8. Breast Diseases

    Science.gov (United States)

    ... bumps, and discharges (fluids that are not breast milk). If you have a breast lump, pain, discharge or skin irritation, see your health care provider. Minor and serious breast problems have similar symptoms. Although many women fear cancer, most breast problems are not cancer. Some common ...

  9. Inhibition of Metastatic Potential in Breast Carcinoma In Vivo and In Vitro through Targeting VEGFRs and FGFRs

    Directory of Open Access Journals (Sweden)

    Ming-Hsien Chien

    2013-01-01

    Full Text Available Angiogenesis and lymphangiogenesis are considered to play key roles in tumor metastasis. Targeting receptor tyrosine kinases essentially involved in the angiogenesis and lymphangiogenesis would theoretically prevent cancer metastasis. However, the optimal multikinase inhibitor for metastasis suppression has yet to be developed. In this study, we evaluated the effect of NSTPBP 0100194-A (194-A, a multikinase inhibitor of vascular endothelial growth factor receptors (VEGFRs/fibroblast growth factor receptors (FGFRs, on lymphangiogenesis and angiogenesis in a mammary fat pad xenograft model of the highly invasive breast cancer cell line 4T1-Luc+. We investigated the biologic effect of 194-A on various invasive breast cancer cell lines as well as endothelial and lymphatic endothelial cells. Intriguingly, we found that 194-A drastically reduced the formation of lung, liver, and lymph node metastasis of 4T1-Luc+ and decreased primary tumor growth. This was associated with significant reductions in intratumoral lymphatic vessel length (LVL and microvessel density (MVD. 194-A blocked VEGFRs mediated signaling on both endothelial and lymphatic endothelial cells. Moreover, 194-A significantly inhibited the invasive capacity induced by VEGF-C or FGF-2 in vitro in both 4T1 and MDA-MB231 cells. In conclusion, these experimental results demonstrate that simultaneous inhibition of VEGFRs/FGFRs kinases may be a promising strategy to prevent breast cancer metastasis.

  10. 荷瘤小鼠髓系来源抑制性细胞对哮喘小鼠气道炎症的影响%Effects of Myeloid Derived Suppressor Cells Derived from 4T1 Tumor-Bearing Mice on Airway Inflammation of Asthmatic Mice

    Institute of Scientific and Technical Information of China (English)

    廖原; 于化鹏; 陈新; 樊慧珍; 龚雨新

    2012-01-01

    Objective To investigate the effect of myeloid derived suppressor cells (MDSCs) on airway inflammation of asthmatic mice. Methods Five male BALB/c mice aged 6 weeks were used for preparing 4T1 tumor bearing mice. Thirty female BALB/c mice aged six weeks were randomly divided into a normal control group,an athmatic model group, and a cell transplantation group. The MDSCs were separated from myeloid tissue of tumor-bearing mice using a magnetic cell sorting system and cultured in RPMI medium 1640 containing GM-CSF. The morphologic characteristics of these cells were observed under light microscope and the phenotypic figures were analyzed with flow cytometry. The mice in the model group and the cell transplantation group were sensitized by ovalbumin and then stimulated with nebulized ovalbumin. The mice in the cell transplantation group were intravenously administered MDSCs which purified by magnetic cell sorting system at 10 days after sensitization. The airway inflammation was evaluated by HE staining. The total and differential cell counts in bronchoalveolar lavage fluid ( BALF) were measured. Results The neutrophil and eosinophil infiltration in pulmonary tissue was dramatically increased in the model group,but not observed in the normal control group and was much milder in the cell transplantation group. The total cell count,the eosinophil and lymphocyte counts in BALF of the model group and the cell transplantation group were significantly higher than those of the normal control group ( P < 0. 05) , and the number of eosinophils in BALF of the cell transplantation group was decreased when compared with that of the model group (P <0. 05). Conclusion MDSCs via intravenous infusion can effectively suppress airway inflammation in a mouse asthma model.%目的 初步探讨髓系来源抑制性细胞( MDSC)对哮喘小鼠气道炎症的影响.方法 将6周龄SPF级BALB/c雄鼠5只制成4T1乳腺癌细胞成瘤小鼠,用于制备MDSC.6周龄SPF级BALB/c雌鼠30只随

  11. A novel histone deacetylase inhibitor augments tamoxifen-mediated attenuation of breast carcinoma growth.

    Science.gov (United States)

    Restall, Christina; Doherty, Judy; Liu, Hong Bin; Genovese, Rosemary; Paiman, Lisa; Byron, Keith A; Anderson, Robin L; Dear, Anthony E

    2009-07-15

    Earlier we generated novel derivatives of the hydroxamate-based histone deacetylase inhibitor (HDACi), Oxamflatin (Ox), which demonstrate considerable HDACi activity. Here the effects of one such derivative, Metacept-1 (MCT-1), alone or in combination with tamoxifen on mammary tumour growth have been assessed in a syngeneic orthotopic model. MCT-1 alone resulted in a trend towards inhibition of growth of 4T1.2 mammary tumours. Since the combination of MCT-1 and tamoxifen up-regulates estrogen receptor expression in 4T1.2 cells in vitro, we tested this combination and found a significant reduction in primary tumour growth over tamoxifen treatment alone. Taken together, these observations suggest that the novel HDACi MCT-1 may warrant further exploration in the treatment of estrogen receptor positive breast carcinoma, particularly when used in combination with conventional agents such as tamoxifen.

  12. Breast Gangrene

    Directory of Open Access Journals (Sweden)

    Husasin Irfan

    2011-08-01

    Full Text Available Abstract Background Breast gangrene is rare in surgical practice. Gangrene of breast can be idiopathic or secondary to some causative factor. Antibiotics and debridement are used for management. Acute inflammatory infiltrate, severe necrosis of breast tissue, necrotizing arteritis, and venous thrombosis is observed on histopathology. The aim of was to study patients who had breast gangrene. Methods A prospective study of 10 patients who had breast gangrene over a period of 6 years were analyzed Results All the patients in the study group were female. Total of 10 patients were encountered who had breast gangrene. Six patients presented with breast gangrene on the right breast whereas four had on left breast. Out of 10 patients, three had breast abscess after teeth bite followed by gangrene, one had iatrogenic trauma by needle aspiration of erythematous area of breast under septic conditions. Four had history of application of belladonna on cutaneous breast abscess and had then gangrene. All were lactating female. Amongst the rest two were elderly, one of which was a diabetic who had gangrene of breast and had no application of belladonna. All except one had debridement under cover of broad spectrum antibiotics. Three patients had grafting to cover the raw area. Conclusion Breast gangrene occurs rarely. Etiology is variable and mutifactorial. Teeth bite while lactation and the iatrogenic trauma by needle aspiration of breast abscess under unsterlised conditions could be causative. Uncontrolled diabetes can be one more causative factor for the breast gangrene. Belladonna application as a topical agent could be inciting factor. Sometimes gangrene of breast can be idiopathic. Treatment is antibiotics and debridement.

  13. Increased utilization of fructose has a positive effect on the development of breast cancer

    Directory of Open Access Journals (Sweden)

    Xiajing Fan

    2017-09-01

    Full Text Available Rapid proliferation and Warburg effect make cancer cells consume plenty of glucose, which induces a low glucose micro-environment within the tumor. Up to date, how cancer cells keep proliferating in the condition of glucose insufficiency still remains to be explored. Recent studies have revealed a close correlation between excessive fructose consumption and breast cancer genesis and progression, but there is no convincing evidence showing that fructose could directly promote breast cancer development. Herein, we found that fructose, not amino acids, could functionally replace glucose to support proliferation of breast cancer cells. Fructose endowed breast cancer cells with the colony formation ability and migratory capacity as effective as glucose. Interestingly, although fructose was readily used by breast cancer cells, it failed to restore proliferation of non-tumor cells in the absence of glucose. These results suggest that fructose could be relatively selectively employed by breast cancer cells. Indeed, we observed that a main transporter of fructose, GLUT5, was highly expressed in breast cancer cells and tumor tissues but not in their normal counterparts. Furthermore, we demonstrated that the fructose diet promoted metastasis of 4T1 cells in the mouse models. Taken together, our data show that fructose can be used by breast cancer cells specifically in glucose-deficiency, and suggest that the high-fructose diet could accelerate the progress of breast cancer in vivo.

  14. Breast; Sein

    Energy Technology Data Exchange (ETDEWEB)

    Bourgier, C.; Garbay, J.R.; Pichenot, C.; Uzan, C.; Delaloge, S.; Andre, F.; Spielmann, M.; Arriagada, R.; Lefkopoulos, D.; Marsigli, H.; Bondiau, P.Y.; Courdi, A.; Lallemand, M.; Peyrotte, I.; Chapellier, C.; Ferrero, J.M.; Chiovati, P.; Baldissera, A.; Frezza, G.; Vicenzi, L.; Palombarini, M.; Martelli, O.; Degli Esposti, C.; Donini, E.; Romagna CDR, E.; Romagna CDF, E.; Benmensour, M.; Bouchbika, Z.; Benchakroun, N.; Jouhadi, H.; Tawfiq, N.; Sahraoui, S.; Benider, A.; Gilliot, O.; Achard, J.L.; Auvray, H.; Toledano, I.; Bourry, N.; Kwiatkowski, F.; Verrelle, P.; Lapeyre, M.; Tebra Mrad, S.; Braham, I.; Chaouache, K.; Bouaouin, N.; Ghorbel, L.; Siala, W.; Sallemi, T.; Guermazi, M.; Frikha, M.; Daou, J.; El Omrani, A.; Chekrine, T.; Mangoni, M.; Castaing, M.; Folino, E.; Livi, L.; Dunant, A.; Mathieu, M.C.; Bitib, G.P.; Arriagada, R.; Marsigli, H

    2007-11-15

    Nine articles treat the question of breast cancer. Three-dimensional conformal accelerated partial breast irradiation: dosimetric feasibility study; test of dose escalation neo-adjuvant radiotherapy focused by Cyberknife in breast cancer; Three dimensional conformal partial irradiation with the technique by the Irma protocol ( dummy run multi centers of the Emilie Romagne area Italy); Contribution of the neo-adjuvant chemotherapy in the treatment of locally evolved cancers of the uterine cervix; Post operative radiotherapy of breast cancers (N0, pN) after neo-adjuvant chemotherapy. Radiotherapy of one or two mammary glands and ganglions areas,The breast cancer at man; breast conservative treatment; breast cancers without histological ganglions invasion; the breast cancer at 70 years old and more women; borderline mammary phyllod tumors and malignant. (N.C.)

  15. Breast Cancer

    Science.gov (United States)

    Breast cancer affects one in eight women during their lives. No one knows why some women get breast cancer, but there are many risk factors. Risks that ... who have family members with breast or ovarian cancer may wish to be tested for the genes. ...

  16. Murine gamma interferon fails to inhibit Toxoplasma gondii growth in murine fibroblasts.

    Science.gov (United States)

    Schwartzman, J D; Gonias, S L; Pfefferkorn, E R

    1990-01-01

    Although treatment of human macrophages or fibroblasts with human gamma interferon results in the inhibition of intracellular Toxoplasma gondii, murine gamma interferon stimulated only murine macrophages, not murine fibroblasts, to inhibit T. gondii. This species difference may be important in understanding the control of acute and chronic toxoplasmosis. PMID:2106497

  17. The kin17 Protein in Murine Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Anelise C. Ramos

    2015-11-01

    Full Text Available kin17 has been described as a protein involved in the processes of DNA replication initiation, DNA recombination, and DNA repair. kin17 has been studied as a potential molecular marker of breast cancer. This work reports the detection and localization of this protein in the murine melanoma cell line B16F10-Nex2 and in two derived subclones with different metastatic potential, B16-8HR and B16-10CR. Nuclear and chromatin-associated protein fractions were analyzed, and kin17 was detected in all fractions, with an elevated concentration observed in the chromatin-associated fraction of the clone with low metastatic potential, suggesting that the kin17 expression level could be a marker of melanoma.

  18. Melanin-originated carbonaceous dots for triple negative breast cancer diagnosis by fluorescence and photoacoustic dual-mode imaging.

    Science.gov (United States)

    Xiao, Wei; Li, Yuan; Hu, Chuan; Huang, Yuan; He, Qin; Gao, Huile

    2017-07-01

    Carbonaceous dots exhibit increasing applications in diagnosis and drug delivery due to excellent photostability and biocompatibility properties. However, relative short excitation and emission of melanin carbonaceous dots (MCDs) limit the applicability in fluorescence bioimaging. Furthermore, the generally poor spatial resolution of fluorescence imaging limits potential in vivo applications. Due to a variety of beneficial properties, in this study, MCDs were prepared exhibiting great potential in fluorescence and photoacoustic dual-mode bioimaging. The MCDs exhibited a long excitation peak at 615nm and emission peak at 650nm, further highlighting the applicability in fluorescence imaging, while the absorbance peak at 633nm renders MCDs suitable for photoacoustic imaging. In vivo, the photoacoustic signal of MCDs was linearly correlated with the concentration of MCDs. Moreover, the MCDs were shown to be taken up into triple negative breast cancer cell line 4T1 in both a time- and concentration-dependent manner. In vivo fluorescence and photoacoustic imaging of subcutaneous 4T1 tumor demonstrated that MCDs could passively target triple negative breast cancer tissue by enhanced permeability and retention effects and may therefore be used for tumor dual-mode imaging. Furthermore, fluorescence distribution in tissue slices suggested that MCDs may distribute in 4T1 tumor with high efficacy. In conclusion, the MCDs studied offer potential application in fluorescence and photoacoustic dual-mode imaging.

  19. Breast augmentation surgery

    Science.gov (United States)

    ... on the underside of your breast, in the natural skin fold. The surgeon places the implant through this ... lift Breast pain Breast reconstruction - implants Breast reconstruction - natural tissue Breast ... wound care - open Review Date 2/10/2015 Updated by: ...

  20. Breast cancer screening

    Science.gov (United States)

    Mammogram - breast cancer screening; Breast exam - breast cancer screening; MRI - breast cancer screening ... performed to screen women to detect early breast cancer when it is more likely to be cured. ...

  1. Breast Reconstruction Alternatives

    Science.gov (United States)

    ... Breast Reconstruction Surgery Breast Cancer Breast Reconstruction Surgery Breast Reconstruction Alternatives Some women who have had a ... chest. What if I choose not to get breast reconstruction? Some women decide not to have any ...

  2. Surgery for Breast Cancer

    Science.gov (United States)

    ... Pregnancy Breast Cancer Breast Cancer Treatment Surgery for Breast Cancer Surgery is a common treatment for breast cancer, ... Relieve symptoms of advanced cancer Surgery to remove breast cancer There are two main types of surgery to ...

  3. Breast Reconstruction with Implants

    Science.gov (United States)

    Breast reconstruction with implants Overview By Mayo Clinic Staff Breast reconstruction is a surgical procedure that restores shape to ... treat or prevent breast cancer. One type of breast reconstruction uses breast implants — silicone devices filled with silicone ...

  4. Breast Cancer Overview

    Science.gov (United States)

    ... Cancer > Breast Cancer > Breast Cancer: Overview Request Permissions Breast Cancer: Overview Approved by the Cancer.Net Editorial Board , ... bean-shaped organs that help fight infection. About breast cancer Cancer begins when healthy cells in the breast ...

  5. Correlation of bone marrow stromal cell-derived exosomes with Hedgehog signaling in the progress of breast cancer%骨髓间充质干细胞源性外泌体与Hedgehog信号通路在乳腺癌发展中的关系研究

    Institute of Scientific and Technical Information of China (English)

    王丹丹; 陈建中; 亢春彦

    2015-01-01

    目的:研究Hedgehog信号通路在骨髓间充质干细胞( BMSCs)来源exosome介导小鼠4T1乳腺癌细胞发展过程中的作用。方法使用梯度离心分离法、差速贴壁培养方法及超速离心法分离C57BL/6小鼠BMSCs及其exosome,使用MTT法、细胞划痕实验及western blot技术分析exosome干预前后4T1癌细胞增殖、迁移和侵袭能力以及Hedgehog信号通路相关蛋白表达情况,之后使用GANT61(Hedgehog信号通路阻断剂)验证Hedgehog信号通路在BM-SCs来源的exosome介导乳腺癌细胞增殖、迁移和侵袭过程中的作用。结果 BMSCs来源的exosome显著上调了4T1细胞Hedgehog信号通路,exosome显著增加了4T1细胞的增殖及迁移、侵袭能力,而这一作用被GANT61所削减。结论 BMSCs来源的exosome能够通过上调Hedgehog信号通路增加4T1小鼠乳腺癌细胞的增殖、迁移及侵袭能力。%Objective To investigate the roles of Hedgehog signaling pathway in the BMSCs derived exosome-in-duced progression of 4T1 mouse breast cancer cells. Methods Prepare the BMSCs and exosome by gradient centrifugation separation, differential adhesion method and ultracentrifugation method;use the MTT test, cell scratch test and western blot to examine the effect of BMSCs-exosome on the proliferation, migration and invasion ability of 4T1 cells, then use the GANT61, an inhibitor of Hedgehog signaling pathway, to test the mechanism of exosome-induced changes in the 4T1 cells. Results BMSCs-exosome significantly up-regulated the Hedgehog signaling pathway of the 4T1 cells. The exosome signifi-cantly increased the proliferation, migaration and invasion ability of 4T1 cells in vitro, and this effect was abolished by GANT61. Conclusions BMSCs derived exosome can promote the proliferation, migration and invasion ability by upregu-late Hedgehog signaling pathway.

  6. Dipyridamole prevents triple-negative breast-cancer progression.

    Science.gov (United States)

    Spano, Daniela; Marshall, Jean-Claude; Marino, Natascia; De Martino, Daniela; Romano, Alessia; Scoppettuolo, Maria Nunzia; Bello, Anna Maria; Di Dato, Valeria; Navas, Luigi; De Vita, Gennaro; Medaglia, Chiara; Steeg, Patricia S; Zollo, Massimo

    2013-01-01

    Dipyridamole is a widely prescribed drug in ischemic disorders, and it is here investigated for potential clinical use as a new treatment for breast cancer. Xenograft mice bearing triple-negative breast cancer 4T1-Luc or MDA-MB-231T cells were generated. In these in vivo models, dipyridamole effects were investigated for primary tumor growth, metastasis formation, cell cycle, apoptosis, signaling pathways, immune cell infiltration, and serum inflammatory cytokines levels. Dipyridamole significantly reduced primary tumor growth and metastasis formation by intraperitoneal administration. Treatment with 15 mg/kg/day dipyridamole reduced mean primary tumor size by 67.5 % (p = 0.0433), while treatment with 30 mg/kg/day dipyridamole resulted in an almost a total reduction in primary tumors (p = 0.0182). Experimental metastasis assays show dipyridamole reduces metastasis formation by 47.5 % in the MDA-MB-231T xenograft model (p = 0.0122), and by 50.26 % in the 4T1-Luc xenograft model (p = 0.0292). In vivo dipyridamole decreased activated β-catenin by 38.64 % (p < 0.0001), phospho-ERK1/2 by 25.05 % (p = 0.0129), phospho-p65 by 67.82 % (p < 0.0001) and doubled the expression of IkBα (p = 0.0019), thus revealing significant effects on Wnt, ERK1/2-MAPK and NF-kB pathways in both animal models. Moreover dipyridamole significantly decreased the infiltration of tumor-associated macrophages and myeloid-derived suppressor cells in primary tumors (p < 0.005), and the inflammatory cytokines levels in the sera of the treated mice. We suggest that when used at appropriate doses and with the correct mode of administration, dipyridamole is a promising agent for breast-cancer treatment, thus also implying its potential use in other cancers that show those highly activated pathways.

  7. Breast Cysts

    Science.gov (United States)

    ... cells may be collected to check for cancer (fine-needle aspiration biopsy). No treatment is necessary for simple breast cysts — those that are fluid-filled and don't cause any symptoms — that are confirmed on breast ultrasound or after a fine-needle aspiration. If the lump persists or feels ...

  8. Flow cytometry of murine spermatocytes.

    Science.gov (United States)

    Gaysinskaya, Valeriya; Bortvin, Alex

    2015-04-01

    Protocols for purification of murine male germ cells by FACS based on Hoechst 33342 (Ho342) dye staining have been reported and optimized. However, the protocols are often challenging to follow, partly due to difficulties related to sample preparation, instrument parameters, data display, and selection strategies. In addition, troubleshooting of flow cytometry experiments usually requires some fluency in technical principles and instrument specifications and settings. This unit describes setup and procedures for analysis and sorting of male meiotic prophase I (MPI) cells and other germ cells. Included are procedures that guide data acquisition, display, gating, and back-gating critical for optimal data visualization and cell sorting. Additionally, a flow cytometry analysis of spermatogenesis-defective testis is provided to illustrate the applicability of the technique to the characterization and purification of cells from mutant testis.

  9. Murine models of ulcerative colitis.

    Science.gov (United States)

    Flynn, Christopher; Levine, Joel; Rosenberg, Daniel W

    2003-06-01

    Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology limited to the large intestine. The disease is prevalent in industrial societies and is associated with specific ethnic populations. A number of murine models, each focused on distinct aspects of the disease process, were developed over the past 20 years to further our understanding of the pathogenesis of UC. These models have been and remain our best resource for the study of the disorder as a result of their homology to human UC and the ease in which they can be manipulated and examined. This review examines and distills what has been leamed from these models and how this information is related back to human UC.

  10. Murine model of TB meningitis.

    Science.gov (United States)

    Gupta, Umesh Datta; Abbas, Ali; Kashyap, Raj Pal Singh; Gupta, Pushpa

    2016-12-01

    Central nervous system (CNS) infections caused by Mycobacterium tuberculosis (MTB) are the most severe forms of extrapulmonary TB (EPTB) due to high levels of mortality and neurological morbidity. Limited studies are available on CNS-TB animal-model development, despite the steady rise in cerebral-TB cases in India over the past decade. This study describes the development of a murine model of CNS-TB using a clinical strain (C3) isolated from the cerebrospinal fluid (CSF) of CNS-TB patients. Groups of mice were infected intravenously with an MTB C3 strain isolated from the CSF of CNS-TB patients in order to mimic the dynamics of actual infection. Brain and lung tissue were evaluated for bacterial burden, as well as histopathology and surrogate markers of TB infection at 30- and 50-days post-infection. Mice infected intravenously with MTB C3 strains showed progressive development of CNS disease, with high bacillary burden in the lungs during the initial stage (30days), which eventually disseminated to the brain at a later stage (50days). All C3-infected mice showed elevated levels of mycobacterial antigens and antibodies, as well as increased T cell adenosine deaminase activity in brain homogenates, which explicitly correlated with mycobacterial load in the brain and chronic brain pathology. High mortality rates (60%) were associated with mice infected with the C3 strain as compared to those of controls. Our findings demonstrated the design of a novel murine model of CNS-TB using a C3 strain and that replicated events of EPTB dissemination. This model will promote efforts to understand the pathogenesis CNS-TB infection for development of improved therapeutic interventions in the future. Copyright © 2016.

  11. Other Considerations for Pregnancy and Breast Cancer

    Science.gov (United States)

    ... Cancer Patient Breast Cancer Patient Breast Cancer Treatment Male Breast Cancer Treatment Breast Cancer Treatment & Pregnancy Breast Cancer Prevention Breast Cancer Screening Health Professional Breast Cancer Treatment Male ... Treatment Breast Cancer Treatment & Pregnancy Breast Cancer Prevention ...

  12. Breast MRI scan

    Science.gov (United States)

    MRI - breast; Magnetic resonance imaging - breast; Breast cancer - MRI; Breast cancer screening - MRI ... radiologist) see some areas more clearly. During the MRI, the person who operates the machine will watch ...

  13. Types of Breast Pumps

    Science.gov (United States)

    ... Devices Consumer Products Breast Pumps Types of Breast Pumps Share Tweet Linkedin Pin it More sharing options ... used for feeding a baby. Types of Breast Pumps There are three basic types of breast pumps: ...

  14. Breast enlargement in males

    Science.gov (United States)

    ... substances can cause breast enlargement: Alcohol Amphetamines Heroin Marijuana Methadone Men who have enlarged breasts may have an increased risk for breast cancer . Breast cancer in men is rare. Signs that ...

  15. Breast Cancer Treatment

    Science.gov (United States)

    ... Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Treatment (PDQ®)–Patient Version General Information About Breast Cancer ... clinical trials before, during, or after starting their cancer treatment. Some clinical trials only include patients who have ...

  16. Breast Cancer Research Update

    Science.gov (United States)

    ... JavaScript on. Feature: Breast Cancer Breast Cancer Research Update Winter 2017 Table of Contents National Cancer Institute ... Addressing Breast Cancer's Unequal Burden / Breast Cancer Research Update Winter 2017 Issue: Volume 11 Number 4 Page ...

  17. Hydrogen-bonded and reduction-responsive micelles loading atorvastatin for therapy of breast cancer metastasis.

    Science.gov (United States)

    Xu, Pengfei; Yu, Haijun; Zhang, Zhiwen; Meng, Qingshuo; Sun, Huiping; Chen, Xianzhi; Yin, Qi; Li, Yaping

    2014-08-01

    Metastasis is one of the major obstacles for the successful therapy of breast cancer. Although increased candidate drugs targeting cancer metastasis are tested, their clinical translation is limited by either serve toxicity or low efficacy. In present work, a nano-drug delivery system loading atorvastatin calcium (Ator) was developed for the efficient suppression of the metastasis of breast cancer. The nano-drug delivery system was constructed by a amphiphilic copolymer of methoxy polyethylene glycol-s-s-vitamin E succinate (mPEG-s-s-VES, PSV), which was consisted of a hydrophilic mPEG1k segment and a hydrophobic VES head, which were conjugated with a linker bearing amide and disulfide groups simultaneously. Self-assembly of PSV and Ator formed Ator-loaded PSV micelles (ASM) with good colloidal stability, high drug loading content (up to 50%) and great encapsulation efficiency (99.09 ± 0.28%). In cellular level, it was found that the ASM could efficiently release the Ator payload into cytosol due to detachment of PEG shell at high intracellular glutathione condition. ASM could significantly inhibit the migration and invasion of 4T1 breast cancer cells with inhibitory rates of 79.2% and 88.5%, respectively. In a 4T1 orthotropic mammary tumor metastatic cancer model, it was demonstrated that ASM could completely blocked the lung and liver metastasis of breast cancer with minimal toxicity owing to enhanced Ator accumulation in tumor and lung as compared with that of free Ator. The down-regulations of metastasis-promoting MMP-9, Twist and uPA proteins were demonstrated as the main underlying mechanism. As a result, ASM could be a promising drug delivery system for the efficient therapy of breast cancer metastasis.

  18. Development of Technologies for Early Detection and Stratification of Breast Cancer

    Science.gov (United States)

    2013-10-01

    fluid phase from fine needle aspirate (FNA) samples from murine tumors in HIM model (Months 1-12). 4b. Develop and submit proposal to IRB for...working to characterize breast cancer biopsy samples with single cell resolution to discover the nature of the underlying heterogeneity in complex...Confirm presence of the single cells in human breast cancer biopsy samples obtained from Buchsbaum (Months 48-60). These studies have not been

  19. Understanding a Breast Cancer Diagnosis

    Science.gov (United States)

    ... Cancer A-Z Breast Cancer Understanding a Breast Cancer Diagnosis If you’ve been diagnosed with breast cancer, ... Prevention Early Detection and Diagnosis Understanding a Breast Cancer Diagnosis Treatment Breast Reconstruction Surgery Living as a Breast ...

  20. Breast Reconstruction with Flap Surgery

    Science.gov (United States)

    Breast reconstruction with flap surgery Overview By Mayo Clinic Staff Breast reconstruction is a surgical procedure that restores shape to ... breast tissue to treat or prevent breast cancer. Breast reconstruction with flap surgery is a type of breast ...

  1. Breast lump

    Science.gov (United States)

    ... a woman are often caused by fibrocystic changes, fibroadenomas, and cysts. Fibrocystic changes are painful, lumpy breasts. ... period, and then improve after your period starts. Fibroadenomas are noncancerous lumps that feel rubbery. They move ...

  2. Breast Reconstruction

    Science.gov (United States)

    ... senos Preguntas Para el Médico Datos Para la Vida Komen El cuidado de sus senos:Consejos útiles ... can help . Cost Federal law requires most insurance plans cover the cost of breast reconstruction. Learn more ...

  3. Breast Augmentation

    Science.gov (United States)

    ... surgery might even improve your body image and self-esteem. If you're looking for perfection, however, you ... www.mayoclinic.org/tests-procedures/breast-augmentation/basics/definition/prc-20021493 . Mayo Clinic Footer Legal Conditions and ...

  4. Breast Lumps

    Science.gov (United States)

    ... You might notice: A distinct lump with definite borders A firm, hard area within your breast A ... MayoClinic.org," "Mayo Clinic Healthy Living," and the triple-shield Mayo Clinic logo are trademarks of Mayo ...

  5. Dense Breasts

    Science.gov (United States)

    ... also appear white on mammography, they can be hidden by or within dense breast tissue. Other imaging ... understanding of the possible charges you will incur. Web page review process: This Web page is reviewed ...

  6. Breast Rash

    Science.gov (United States)

    ... rashes/rash-in-adults. Accessed Dec. 29, 2016. Papadakis MA, et al., eds. Breast disorders. In: Current ... http://www.accessmedicine.com. Accessed Dec. 28, 2016. Papadakis MA, et al., eds. Dermatologic disorders. In: Current ...

  7. Targeting the cancer-associated fibroblasts as a treatment in triple-negative breast cancer

    Science.gov (United States)

    Takai, Ken; Le, Annie; Weaver, Valerie M.; Werb, Zena

    2016-01-01

    Increased collagen expression in tumors is associated with increased risk of metastasis, and triple-negative breast cancer (TNBC) has the highest propensity to develop distant metastases when there is evidence of central fibrosis. Transforming growth factor-β (TGF-β) ligands regulated by cancer-associated fibroblasts (CAFs) promote accumulation of fibrosis and cancer progression. In the present study, we have evaluated TNBC tumors with enhanced collagen to determine whether we can reduce metastasis by targeting the CAFs with Pirfenidone (PFD), an anti-fibrotic agent as well as a TGF-β antagonist. In patient-derived xenograft models, TNBC tumors exhibited accumulated collagen and activated TGF-β signaling, and developed lung metastasis. Next, primary CAFs were established from 4T1 TNBC homograft tumors, TNBC xenograft tumors and tumor specimens of breast cancer patients. CAFs promoted primary tumor growth with more fibrosis and TGF-β activation and lung metastasis in 4T1 mouse model. We then examined the effects of PFD in vitro and in vivo. We found that PFD had inhibitory effects on cell viability and collagen production of CAFs in 2D culture. Furthermore, CAFs enhanced tumor growth and PFD inhibited the tumor growth induced by CAFs by causing apoptosis in the 3D co-culture assay of 4T1 tumor cells and CAFs. In vivo, PFD alone inhibited tumor fibrosis and TGF-β signaling but did not inhibit tumor growth and lung metastasis. However, PFD inhibited tumor growth and lung metastasis synergistically in combination with doxorubicin. Thus, PFD has great potential for a novel clinically applicable TNBC therapy that targets tumor-stromal interaction. PMID:27756881

  8. Histone deacetylase inhibitors improve the replication of oncolytic herpes simplex virus in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    James J Cody

    Full Text Available New therapies are needed for metastatic breast cancer patients. Oncolytic herpes simplex virus (oHSV is an exciting therapy being developed for use against aggressive tumors and established metastases. Although oHSV have been demonstrated safe in clinical trials, a lack of sufficient potency has slowed the clinical application of this approach. We utilized histone deacetylase (HDAC inhibitors, which have been noted to impair the innate antiviral response and improve gene transcription from viral vectors, to enhance the replication of oHSV in breast cancer cells. A panel of chemically diverse HDAC inhibitors were tested at three different doses (LD50 for their ability to modulate the replication of oHSV in breast cancer cells. Several of the tested HDAC inhibitors enhanced oHSV replication at low multiplicity of infection (MOI following pre-treatment of the metastatic breast cancer cell line MDA-MB-231 and the oHSV-resistant cell line 4T1, but not in the normal breast epithelial cell line MCF10A. Inhibitors of class I HDACs, including pan-selective compounds, were more effective for increasing oHSV replication compared to inhibitors that selectively target class II HDACs. These studies demonstrate that select HDAC inhibitors increase oHSV replication in breast cancer cells and provides support for pre-clinical evaluation of this combination strategy.

  9. Genomic analysis of a spontaneous model of breast cancer metastasis to bone reveals a role for the extracellular matrix.

    Science.gov (United States)

    Eckhardt, Bedrich L; Parker, Belinda S; van Laar, Ryan K; Restall, Christina M; Natoli, Anthony L; Tavaria, Michael D; Stanley, Kym L; Sloan, Erica K; Moseley, Jane M; Anderson, Robin L

    2005-01-01

    A clinically relevant model of spontaneous breast cancer metastasis to multiple sites, including bone, was characterized and used to identify genes involved in metastatic progression. The metastatic potential of several genetically related tumor lines was assayed using a novel real-time quantitative RT-PCR assay of tumor burden. Based on this assay, the tumor lines were categorized as nonmetastatic (67NR), weakly metastatic to lymph node (168FARN) or lung (66cl4), or highly metastatic to lymph node, lung, and bone (4T1.2 and 4T1.13). In vitro assays that mimic stages of metastasis showed that highly metastatic tumors lines were more adhesive, invasive, and migratory than the less metastatic lines. To identify metastasis-related genes in this model, each metastatic tumor was array profiled against the nonmetastatic 67NR using 15,000 mouse cDNA arrays. A significant proportion of genes relating to the extracellular matrix had elevated expression in highly metastatic tumors. The role of one of these genes, POEM, was further investigated in the model. In situ hybridization showed that POEM expression was specific to the tumor epithelium of highly metastatic tumors. Decreased POEM expression in 4T1.2 tumors significantly inhibited spontaneous metastasis to the lung, bone, and kidney. Taken together, our data support a role for the extracellular matrix in metastatic progression and describe, for the first time, a role for POEM in this process.

  10. Breast fibromatosis associated with breast implants.

    Science.gov (United States)

    Seo, Yoon Nae; Park, Young Mi; Yoon, Hye Kyoung; Lee, Sun Joo; Choo, Hye Jung; Ryu, Ji Hwa

    2015-09-01

    Fibromatosis refers to an extra-abdominal desmoid tumor or aggressive fibromatosis. Breast fibromatosis can develop in association with the capsule around a breast implant, although reports of cases of fibromatosis associated with breast implants are rare. As the demand for breast augmentation has increased, it is important to understand the diseases associated with breast implants. In the present report, we describe a case of breast fibromatosis that developed adjacent to a breast implant and demonstrated a relatively well-defined border even though it invaded the surrounding structures. We also explore the specific imaging features for diagnosing breast fibromatosis in association with implants by reviewing previous literature.

  11. Apoptosis in irradiated murine tumors.

    Science.gov (United States)

    Stephens, L C; Ang, K K; Schultheiss, T E; Milas, L; Meyn, R E

    1991-09-01

    Early radiation responses of transplantable murine ovarian (OCaI) and hepatocellular (HCaI) carcinomas were examined at 6, 24, 48, 96, and 144 h after single photon doses of 25, 35, or 45 Gy. Previous studies using tumor growth delay and tumor radiocurability assays had shown OCaI tumors to be relatively radiosensitive and HCaI tumors to be radioresistant. At 6 h, approximately 20% of nuclei in OCaI tumors showed aberrations characteristic of cell death by apoptosis. This contrasted to an incidence of 3% in HCaI tumors. Mitotic activity was eliminated in OCaI tumors but was only transiently suppressed in HCaI tumors. At 24-96 h, OCaI tumors continued to display apoptosis and progressive necrosis, whereas HCaI tumors responded by exhibiting marked pleomorphism. Factors other than mitotic activity may influence tumor radiosensitivity, and one of these may be susceptibility to induction of apoptosis (programmed cell death), because this was a prominent early radiation response by the radiosensitive OCaI tumors.

  12. Anti-breast cancer properties and toxicity of Dillenia suffruticosa root aqueous extract in BALB/c mice

    Institute of Scientific and Technical Information of China (English)

    Latifah Saiful Yazan; Yong Sze Ong; Nur Elena Zaaba; Razana Mohd Ali; Jhi Biau Foo; Yin Sim Tor

    2015-01-01

    Objective: To determine the anti-breast cancer activities and the safety oral consumption of Dillenia suffruticosa root aqueous extract (DRAE) in BALB/c mice. Methods: In the anti-breast cancer study, female BALB/c mice were divided into five groups (n = 12), which were (1) positive control (with breast cancer, untreated), (2) negative control (without breast cancer, untreated) and other three groups of mice with breast cancer treated with 1 000, 500 and 250 mg/kg of DRAE, respectively, by oral gavage for 28 days. All mice except from the negative control group were injected into the mammary fat pad with 4T1 cells (1 × 105 4T1 cells/0.1 mL of phosphate buffer solution). DRAE was administered orally on Day 11 after the tumor has developed. Results: The tumor volume of the 1 000 mg/kg of DRAE group reduced significantly compared to the positive control while treatment with 500 mg/kg of DRAE had signif-icantly inhibited metastasis to the heart. In the acute toxicity study, treatment with up to 5 000 mg/kg of DRAE was not toxic to the animals, indicating its safety when a large amount of this plant extract was ingested. Based on the sub-acute toxicity study, treatment of the highest dose of DRAE (1 000 mg/kg) had mild liver toxicity indicated by mild focal hemorrhage. Conclusions: DRAE possesses anti-breast cancer properties but at the same time it shows mild toxicity to the liver. The non observable adverse effect dose for DRAE is 500 mg/kg.

  13. Photo-nano immunotherapy for metastatic breast cancer using synergistic single-walled carbon nanotubes and glycated chitosan

    Science.gov (United States)

    Zhou, Feifan; Hasanjee, Aamr; Doughty, Austin; West, Connor; Liu, Hong; Chen, Wei R.

    2015-03-01

    In our previous work, we constructed a multifunctional nano system, using single-walled carbon nanotube (SWNT) and glycated chitosan (GC), which can synergize photothermal and immunological effects. To further confirm the therapy efficacy, with a metastatic mouse mammary tumor model (4T1), we investigate the therapy effects and immune response induced by SWNT-GC, under laser irradiation. Laser+SWNT-GC treatment not only suppressed the prime tumor, but also induced antitumor immune response. It could be developed into a promising treatment modality for the metastatic breast cancer.

  14. A Combined Nutritional and Immunological Intervention to Activate Natural Cytotoxicity Against Breast Cancer Cells In Vitro and In Vivo

    Science.gov (United States)

    2011-09-01

    hematogenous or lymphatic routes, similar to that of human breast cancer. In addition, 4T1 cells are resistant to growth inhibition by 6-thioguanine...correlated well with the weight of the primary tumor (Fig. 2B, P < 0.0001), suggesting a chronic response of the immune system to the growth of the tumor...2009. 5. Sanz MA and Lo-Coco F: Modern approaches to treating acute promyelo- cytic leukemia . J Clin Oncol 29, 495–503, 2011. 6. Ng SC, Kamm MA

  15. Selenium analogues of raloxifene as promising antiproliferative agents in treatment of breast cancer.

    Science.gov (United States)

    Arsenyan, Pavel; Paegle, Edgars; Domracheva, Ilona; Gulbe, Anita; Kanepe-Lapsa, Iveta; Shestakova, Irina

    2014-11-24

    Synthetic protocols for the preparation of selenium analogues of raloxifene were elaborated. General aim of the current research is to improve the positive impact of selenium atom introduction in drug design. Antiproliferative activity on CCL-8 (mouse sarcoma), MDA-MB-435s (human melanoma), MES-SA (human uterus sarcoma), MCF-7 (human breast adenocarcinoma), HT-1080 (human fibrosarcoma), MG-22A (mouse hepatoma) tumor cell lines, and normal cell line NIH 3T3 (mouse fibroblasts) was studied. Influence of aminoethoxy "tail" and benzoyl group position on SAR was discussed. Results of in vivo studies on BALB/c female mice with 4T1 cell induced breast cancer model showed that selenium analogue of raloxifene is able to suppress estrogen-depending tumor growth.

  16. Hornerin, an S100 family protein, is functional in breast cells and aberrantly expressed in breast cancer

    Directory of Open Access Journals (Sweden)

    Fleming Jodie M

    2012-06-01

    Full Text Available Abstract Background Recent evidence suggests an emerging role for S100 protein in breast cancer and tumor progression. These ubiquitous proteins are involved in numerous normal and pathological cell functions including inflammatory and immune responses, Ca2+ homeostasis, the dynamics of cytoskeleton constituents, as well as cell proliferation, differentiation, and death. Our previous proteomic analysis demonstrated the presence of hornerin, an S100 family member, in breast tissue and extracellular matrix. Hornerin has been reported in healthy skin as well as psoriatic and regenerating skin after wound healing, suggesting a role in inflammatory/immune response or proliferation. In the present study we investigated hornerin’s potential role in normal breast cells and breast cancer. Methods The expression levels and localization of hornerin in human breast tissue, breast tumor biopsies, primary breast cells and breast cancer cell lines, as well as murine mammary tissue were measured via immunohistochemistry, western blot analysis and PCR. Antibodies were developed against the N- and C-terminus of the protein for detection of proteolytic fragments and their specific subcellular localization via fluorescent immunocytochemisty. Lastly, cells were treated with H2O2 to detect changes in hornerin expression during induction of apoptosis/necrosis. Results Breast epithelial cells and stromal fibroblasts and macrophages express hornerin and show unique regulation of expression during distinct phases of mammary development. Furthermore, hornerin expression is decreased in invasive ductal carcinomas compared to invasive lobular carcinomas and less aggressive breast carcinoma phenotypes, and cellular expression of hornerin is altered during induction of apoptosis. Finally, we demonstrate the presence of post-translational fragments that display differential subcellular localization. Conclusions Our data opens new possibilities for hornerin and its

  17. Detection of cellular senescence within human invasive breast carcinomas distinguishes different breast tumor subtypes.

    Science.gov (United States)

    Cotarelo, Cristina L; Schad, Arno; Kirkpatrick, Charles James; Sleeman, Jonathan P; Springer, Erik; Schmidt, Marcus; Thaler, Sonja

    2016-11-15

    Oncogene-induced senescence is thought to act as a barrier to tumorigenesis by arresting cells at risk of malignant transformation. Nevertheless, numerous findings suggest that senescent cells may conversely promote tumor progression through the development of the senescence-associated secretome they produce. It is likely that the composition and the physiological consequences mediated by the senescence secretome are dependent on the oncogenes that trigger the senescence program. Breast cancer represents a heterogenous disease that can be divided into breast cancer subtypes due to different subsets of genetic and epigenetic abnormalities. As tumor initiation and progression of these breast cancer subtypes is triggered by diverse oncogenic stimuli, differences in the senescence secretomes within breast tumors might be responsible for tumor initiation, progression, metastasis and therapeutic response. Many studies have addressed the role of senescence as a barrier to tumor progression using murine xenograft models. However, few investigations have been performed to elucidate the degree to which senescent tumor cells are present within untreated human tumors, and if present, whether these senescent tumor cells may play a role in disease progression. In the present study we analysed the appearance of senescent cells within invasive breast cancers. Detection of cellular senescence by the use of SAβ-galactosidase (SAβ-gal) staining within invasive breast carcinoms from 129 untreated patients revealed differences in the amount of SAβ-gal+ tumor cells between breast cancer subtypes. The highest percentages of SAβ-gal+ tumor cells were found in HER2-positive and luminal A breast carcinomas whereas triple negative tumors showed either little or no positivity.

  18. A mouse model for triple-negative breast cancer tumor-initiating cells (TNBC-TICs exhibits similar aggressive phenotype to the human disease

    Directory of Open Access Journals (Sweden)

    Kau Punit

    2012-03-01

    Full Text Available Abstract Background Triple-negative breast cancer (TNBC exhibit characteristics quite distinct from other kinds of breast cancer, presenting as an aggressive disease--recurring and metastasizing more often than other kinds of breast cancer, without tumor-specific treatment options and accounts for 15% of all types of breast cancer with higher percentages in premenopausal African-American and Hispanic women. The reason for this aggressive phenotype is currently the focus of intensive research. However, progress is hampered by the lack of suitable TNBC cell model systems. Methods To understand the mechanistic basis for the aggressiveness of TNBC, we produced a stable TNBC cell line by sorting for 4T1 cells that do not express the estrogen receptor (ER, progesterone receptor (PgR or the gene for human epidermal growth factor receptor 2 (HER2. As a control, we produced a stable triple-positive breast cancer (TPBC cell line by transfecting 4T1 cells with rat HER2, ER and PgR genes and sorted for cells with high expression of ER and PgR by flow cytometry and high expression of the HER2 gene by Western blot analysis. Results We isolated tumor-initiating cells (TICs by sorting for CD24+/CD44high/ALDH1+ cells from TNBC (TNBC-TICs and TPBC (TPBC-TICs stable cell lines. Limiting dilution transplantation experiments revealed that CD24+/CD44high/ALDH1+ cells derived from TNBC (TNBC-TICs and TPBC (TPBC-TICs were significantly more effective at repopulating the mammary glands of naïve female BALB/c mice than CD24-/CD44-/ALDH1- cells. Implantation of the TNBC-TICs resulted in significantly larger tumors, which metastasized to the lungs to a significantly greater extent than TNBC, TPBC-TICs, TPBC or parental 4T1 cells. We further demonstrated that the increased aggressiveness of TNBC-TICs correlates with the presence of high levels of mouse twenty-five kDa heat shock protein (Hsp25/mouse HspB1 and seventy-two kDa heat shock protein (Hsp72/HspA1A. Conclusions

  19. Breast Cancer Surgery

    Science.gov (United States)

    FACTS FOR LIFE Breast Cancer Surgery The goal of breast cancer surgery is to remove the whole tumor from the breast. Some lymph nodes ... might still be in the body. Types of breast cancer surgery There are two types of breast cancer ...

  20. Breast Lift (Mastopexy)

    Science.gov (United States)

    Tests and Procedures Breast lift By Mayo Clinic Staff A breast lift — also known as mastopexy — is a surgical procedure to change the shape of your breasts. During a breast lift, excess skin is removed and breast tissue is ...

  1. Breast awareness and screening.

    Science.gov (United States)

    Harmer, Victoria

    Breast cancer is the most commonly diagnosed cancer in the UK. Breast awareness and screening, along with better treatment, can significantly improve outcomes, and more women than ever are now surviving the disease. This article discusses breast awareness and screening, symptoms and risk factors for breast cancer, and how nurses can raise breast awareness and screening uptake.

  2. High-field (9.4 T) ~1H magnetic resonance microscopy of mouse brain

    Institute of Scientific and Technical Information of China (English)

    丁广良; 胡红兵; 李丽云; 叶朝辉

    1997-01-01

    The FLASH and STEAM pulse sequences were used to perform the microimaging and localized spectroscopy of brain of living and dead mice, respectively. The phase-shift presaturation approach was used to sup-press water NMR signal. The experimental results show that the differences in localized spectra and MR images of brain between live and dead mice can be observed by means of magnetic resonance microscopy.

  3. Nifuroxazide induces apoptosis and impairs pulmonary metastasis in breast cancer model.

    Science.gov (United States)

    Yang, F; Hu, M; Lei, Q; Xia, Y; Zhu, Y; Song, X; Li, Y; Jie, H; Liu, C; Xiong, Y; Zuo, Z; Zeng, A; Li, Y; Yu, L; Shen, G; Wang, D; Xie, Y; Ye, T; Wei, Y

    2015-03-26

    Breast carcinoma is the most common female cancer with considerable metastatic potential. Signal transducers and activators of the transcription 3 (Stat3) signaling pathway is constitutively activated in many cancers including breast cancer and has been validated as a novel potential anticancer target. Here, we reported our finding with nifuroxazide, an antidiarrheal agent identified as a potent inhibitor of Stat3. The potency of nifuroxazide on breast cancer was assessed in vitro and in vivo. In this investigation, we found that nifuroxazide decreased the viability of three breast cancer cell lines and induced apoptosis of cancer cells in a dose-dependent manner. In addition, western blot analysis demonstrated that the occurrence of its apoptosis was associated with activation of cleaved caspases-3 and Bax, downregulation of Bcl-2. Moreover, nifuroxazide markedly blocked cancer cell migration and invasion, and the reduction of phosphorylated-Stat3(Tyr705), matrix metalloproteinase (MMP) MMP-2 and MMP-9 expression were also observed. Furthermore, in our animal experiments, intraperitoneal administration of 50 mg/kg/day nifuroxazide suppressed 4T1 tumor growth and blocked formation of pulmonary metastases without detectable toxicity. Meanwhile, histological and immunohistochemical analyses revealed a decrease in Ki-67-positive cells, MMP-9-positive cells and an increase in cleaved caspase-3-positive cells upon nifuroxazide. Notably, nifuroxazide reduced the number of myeloid-derived suppressor cell in the lung. Our data indicated that nifuroxazide may potentially be a therapeutic agent for growth and metastasis of breast cancer.

  4. Yin-yang effect of tumor infiltrating B cells in breast cancer: From mechanism to immunotherapy.

    Science.gov (United States)

    Zhang, Zhigang; Zhu, Ying; Wang, Zhen; Zhang, Ting; Wu, Pin; Huang, Jian

    2017-05-01

    Breast cancer cells secrete chemokines, such as CXCL13, and antigens or express high endothelial venules, attracting B cells to infiltrate into the tumor microenvironment and play a "yin-yang" effect. They not only enhance the anti-tumor immune effect via secreting antibodies and influencing the Fas/FasL, CXCR4/CXCL12 and perforin pathways but they also promote the tumor to form a suppressive milieu by producing immunomodulatory factors and cytokines or using cell-to-cell education to induce the generation of Tregs or myeloid-derived suppressor cells (MDSCs). Currently, most studies on breast cancer tissue have indicated that B cell infiltration could predict better survival and response to therapy, but two studies have reported opposite results. In a 4T1 tumor-bearing BALB/c mice model, B cell-based immunotherapies were administered, but the efficiency was unstable. Herein, we review the "yin-yang" effect of B cells in breast cancer and discuss B cell-based immunotherapy. B cells are complex aggregates, and breast cancer is a heterogeneous disease. Further studies are urgently required to define the B cell subsets and to discover ways to use B cell-based immunotherapy in breast cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Cytotoxic Effects of Biosynthesized Zinc Oxide Nanoparticles on Murine Cell Lines

    Directory of Open Access Journals (Sweden)

    Farideh Namvar

    2015-01-01

    Full Text Available The aim of this study is to evaluate the in vitro cytotoxic activity and cellular effects of previously prepared ZnO-NPs on murine cancer cell lines using brown seaweed (Sargassum muticum aqueous extract. Treated cancer cells with ZnO-NPs for 72 hours demonstrated various levels of cytotoxicity based on calculated IC50 values using MTT assay as follows: 21.7 ± 1.3 μg/mL (4T1, 17.45 ± 1.1 μg/mL (CRL-1451, 11.75 ± 0.8 μg/mL (CT-26, and 5.6 ± 0.55 μg/mL (WEHI-3B, respectively. On the other hand, ZnO-NPs treatments for 72 hours showed no toxicity against normal mouse fibroblast (3T3 cell line. On the other hand, paclitaxel, which imposed an inhibitory effect on WEHI-3B cells with IC50 of 2.25 ± 0.4, 1.17 ± 0.5, and 1.6 ± 0.09 μg/mL after 24, 48, and 72 hours treatment, respectively, was used as positive control. Furthermore, distinct morphological changes were found by utilizing fluorescent dyes; apoptotic population was increased via flowcytometry, while a cell cycle block and stimulation of apoptotic proteins were also observed. Additionally, the present study showed that the caspase activations contributed to ZnO-NPs triggered apoptotic death in WEHI-3 cells. Thus, the nature of biosynthesis and the therapeutic potential of ZnO-NPs could prepare the way for further research on the design of green synthesis therapeutic agents, particularly in nanomedicine, for the treatment of cancer.

  6. Krüppel-like Factor 4 Inhibits Tumorigenic Progression and Metastasis in a Mouse Model of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jennifer L Yori

    2011-07-01

    Full Text Available Krüppel-like factor 4 (KLF4 is a zinc finger transcription factor that functions as an oncogene or tumor suppressor in a highly tissue-specific cell-dependent manner. However, its precise role in breast cancer and metastasis remains unclear. Here, we show that transient adenoviral expression of KLF4 in the 4T1 orthotopic mammary cancer model significantly attenuated primary tumor growth as well as micrometastases to the lungs and liver. These results can be attributed, in part, to decreased proliferation and increased apoptosis. Further supporting a tumor-suppressive role for KLF4 in the breast, we found that KLF4 expression is lost in a mouse model of HER2/NEU/ERBB2-positive breast cancer. To determine whether enforced KLF4 expression could alter tumor latency in these mice, we used a doxycycline-inducible expression model in the context of the MMTV-Neu transgene. Surprisingly, tumors that developed in this model also lost KLF4 expression, suggesting negative selection for sustained expression. We have previously reported that KLF4 inhibits epithelial-to-mesenchymal transition (EMT, a preliminary step in metastatic progression. Overexpression of KLF4 in 4T1 cells led to a significant reduction in the expression of Snail, a key mediator of EMT and metastasis. Conversely, KLF4 silencing increased Snail expression in the nontransformed MCF-10A cell line. Collectively, these data demonstrate the first functional, in vivo evidence for KLF4 as a tumor suppressor in breast cancer cells. Furthermore, our findings suggest an inhibitory role for KLF4 during breast cancer metastases that functions, in part, through repression of Snail.

  7. Ultrasound-Guided Breast Biopsy

    Science.gov (United States)

    ... Professions Site Index A-Z Ultrasound-Guided Breast Biopsy An ultrasound-guided breast biopsy uses sound waves ... Guided Breast Biopsy? What is Ultrasound-Guided Breast Biopsy? Lumps or abnormalities in the breast are often ...

  8. Stereotactic (Mammographically Guided) Breast Biopsy

    Science.gov (United States)

    ... Resources Professions Site Index A-Z Stereotactic Breast Biopsy Stereotactic breast biopsy uses mammography – a specific type ... Breast Biopsy? What is Stereotactic (Mammographically Guided) Breast Biopsy? Lumps or abnormalities in the breast are often ...

  9. The synergistic effects of radiofrequency ablation (RFA) with glycated chitosan for inhibiting the metastasis of breast cancer

    Science.gov (United States)

    Chiu, Hsin-Yu; Leu, Jyh-Der; Chen, Wei R.; Lee, Yi-Jang

    2016-03-01

    Breast cancer is increasing with years in Taiwan because of dietary style, life behavior and several social-physiological factors. According to the record of Bureau of Health Promotion in Taiwan, the incidence of breast cancer is top one, and the mortality of that is top one cancer type in women. Compared with USA, most of breast cancer cases found in Taiwanese women have reached to stage 2 or 3. Current therapeutic strategies for breast cancer include surgery, radiation therapy, chemotherapy, hormone therapy and targeted therapy. However, these methods used for curing the late-stage breast cancer remains rare. Because the metastasis is the major problem of late-stage breast cancer, it is of interest to investigate whether a systemic therapy can reduce the symptoms of cancer. The immunotherapy, particularly an induction of autoimmune system, is probably important for the treatment of late-stage breast cancer. Glycated chitosan (GC) is derived from chitosan, a linear polysaccharide composed of D-glucosamine and N-acetyl-D-glucosamine through β-(1-4) linkage. Several lines of evidence have shown that GC is an immunoadjuvant that can target on primary and metastatic tumors formed in animal and human patients. In our previous data, GC was demonstrated to decrease the motility and invasion of mammalian breast cancer cells in vitro and in vivo. Radiofrequency ablation (RFA) is dependent on a small generator that delivers high frequency alternating electric current directly to burn a tumor lesion. Therefore, the temperature may reach up to above 60 °C. In this study, we used 4T1 mouse breast cancer cell that is the approximately equal to stage 4 of human breast cancer. And triple modality reporter gene (3R) was delivered into the cells using transfected piggyBac, a transposable element for observation of tumor growth and metastasis in vivo. Data showed that growth and metastasis of tumors smaller than 500mm3 were entirely suppressed by RFA-GC combination treatment

  10. [Breast ductoscopy].

    Science.gov (United States)

    Sharon, Eran; Avin, Ilan D; Leong, Wey

    2011-02-01

    The majority of benign and malignant breast diseases originate in the ductal system. Breast ductoscopy (BD) allows direct access to this ductal system and thus holds great promise in the diagnosis and surgical management of a number of breast diseases. BD was first developed over 20 years ago to investigate nipple discharge. Indeed, till now, this remains the most common indication. However, BD technology has been further developed for a variety of new clinical applications. For example, BD-guided ductal ravage combined with molecular and genetic analysis can be a powerful screening tool for women at high-risk of breast cancer. BD can also be used during lumpectomy to identify additional radiographically occult disease. This refined intraoperative margin assessment can help surgeons to achieve clear margins at the first excision while optimizing the extent of resection. In the future, this same precise intraoperative margin assessment may facilitate a variety of local ablative techniques including laser Over time, BD is likely to evolve beyond its current technological limitations to realize its full diagnostic and therapeutic potential. The article describes the technique of BD, reviews its evolution and discusses current and future applications.

  11. Breast cancer

    CERN Multimedia

    2002-01-01

    "Cancer specialists will soon be able to compare mammograms with computerized images of breast cancer from across Europe, in a bid to improve diagnosis and treatment....The new project, known as MammoGrid, brings together computer and medical imaging experts, cancer specialists, radiologists and epidemiologists from Bristol, Oxford, Cambridge, France and Italy" (1 page).

  12. Breast reduction

    Science.gov (United States)

    ... may need a mammogram before the surgery. Your plastic surgeon will do a routine breast exam. You may ... the first year, but will then fade. The surgeon will make every ... the scars should not be noticeable, even in low-cut clothing.

  13. Targeting CD81 to Prevent Metastases in Breast Cancer

    Science.gov (United States)

    2015-10-01

    lacking CD81 (4T1CD81KO): We used CRISPR -Cas9 methodology to knockout CD81 in 4T1 parental and 4T1-Luc cells, Figure 5 demonstrates complete lack of CD81...expression in these 4T1 tumors. Figure 5: Generation of 4T1 cell lines in which CD81 was knocked out by CRISPR -Cas9 methodology. Shown is CD81...that expressing exogenous CD81 in a human melanoma cell line enhanced its migrating, invasive and metastatic abilities in a xenograft model (27). This

  14. Breast reconstruction - implants

    Science.gov (United States)

    ... After a mastectomy , some women choose to have cosmetic surgery to remake their breast. This type of surgery ... to the breast or the new nipple. Having cosmetic surgery after breast cancer can improve your sense of ...

  15. Breast lift (mastopexy) - slideshow

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/presentations/100188.htm Breast lift (mastopexy) - series—Incisions To use the sharing features ... to slide 3 out of 3 Overview Breast lift (mastopexy) is usually performed for drooping breasts, which ...

  16. Breast Cancer Disparities

    Science.gov (United States)

    ... 2.65 MB] Read the MMWR Science Clips Breast Cancer Black Women Have Higher Death Rates from Breast ... of Page U.S. State Info Number of Additional Breast Cancer Deaths Among Black Women, By State SOURCE: National ...

  17. Male Breast Cancer

    Science.gov (United States)

    ... breast cancer include exposure to radiation, a family history of breast cancer, and having high estrogen levels, which can happen with diseases like cirrhosis or Klinefelter's syndrome. Treatment for male breast cancer is usually ...

  18. Cloning and expression of murine immune interferon cDNA.

    OpenAIRE

    1983-01-01

    The murine immune interferon (IFN-gamma) gene was cloned and expressed under control of the simian virus 40 early promoter in the monkey COS-1 cell line. A protein is secreted from these cells having the biological, antigenic, and biochemical characteristics of natural murine IFN-gamma. Cloned murine IFN-gamma cDNAs were obtained by using RNA from both mitogen-induced murine spleens and the transfected COS cells, and both code for identical proteins. The mature murine IFN-gamma encoded is 136...

  19. Structure of the murine Thy-1 gene

    NARCIS (Netherlands)

    V. Giguere; K-I. Isobe; F.G. Grosveld (Frank)

    1985-01-01

    textabstractWe have cloned the murine Thy-1.1 (AKR) and Thy-1.2 (Balb/c) genes. The complete exon/intron structure and the nucleotide sequence of the Thy-1.2 gene was determined. The gene contains four exons and three intervening sequences. The complete transcriptional unit gives rise to a tissue an

  20. Reemergence of Murine Typhus in the US

    Centers for Disease Control (CDC) Podcasts

    2015-04-21

    Dr. Lucas Blanton discusses the Reemergence of Murine Typhus in Galveston Texas in 2013.  Created: 4/21/2015 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 4/27/2015.

  1. Breast cancer in pregnancy.

    Science.gov (United States)

    Krishna, Iris; Lindsay, Michael

    2013-09-01

    Pregnancy-associated breast cancer is defined as breast cancer diagnosed during pregnancy or in the first postpartum year. Breast cancer is one of the more common malignancies to occur during pregnancy and, as more women delay childbearing, the incidence of breast cancer in pregnancy is expected to increase. This article provides an overview of diagnosis, staging, and treatment of pregnancy-associated breast cancer. Recommendations for management of breast cancer in pregnancy are discussed.

  2. Breast reconstruction after breast cancer.

    Science.gov (United States)

    Serletti, Joseph M; Fosnot, Joshua; Nelson, Jonas A; Disa, Joseph J; Bucky, Louis P

    2011-06-01

    After reading this article, the participant should be able to: 1. Describe the mental, emotional, and physical benefits of reconstruction in breast cancer patients. 2. Compare the most common techniques of reconstruction in patients and detail benefits and risks associated with each. 3. Outline different methods of reconstruction and identify the method considered best for the patient based on timing of the procedures, body type, adjuvant therapies, and other coexisting conditions. 4. Distinguish between some of the different flaps that can be considered for autologous reconstruction. Breast cancer is unfortunately a common disease affecting millions of women, often at a relatively young age. Reconstruction following mastectomy offers women an opportunity to mollify some of the emotional and aesthetic effects of this devastating disease. Although varying techniques of alloplastic and autologous techniques are available, all strive to achieve the same goal: the satisfactory reformation of a breast mound that appears as natural as possible without clothing and at the very least is normal in appearance under clothing. This article summarizes the various approaches to breast reconstruction and offers a balanced view of the risks and benefits of each, all of which in the end offer the opportunity for excellent and predictable results with a high degree of patient satisfaction.

  3. Transcription factor Fos-related antigen 1 is an effective target for a breast cancer vaccine

    Science.gov (United States)

    Luo, Yunping; Zhou, He; Mizutani, Masato; Mizutani, Noriko; Reisfeld, Ralph A.; Xiang, Rong

    2003-07-01

    Protection against breast cancer was achieved with a DNA vaccine against murine transcription factor Fos-related antigen 1, which is overexpressed in aggressively proliferating D2F2 murine breast carcinoma. Growth of primary s.c. tumor and dissemination of pulmonary metastases was markedly suppressed by this oral DNA vaccine, carried by attenuated Salmonella typhimurium, encoding murine Fos-related antigen 1, fused with mutant polyubiquitin, and cotransformed with secretory murine IL-18. The life span of 60% of vaccinated mice was tripled in the absence of detectable tumor growth after lethal tumor cell challenge. Immunological mechanisms involved activation of T, natural killer, and dendritic cells, as indicated by up-regulation of their activation markers and costimulatory molecules. Markedly increased specific target cell lysis was mediated by both MHC class I-restricted CD8+ T cells and natural killer cells isolated from splenocytes of vaccinated mice, including a significant release of proinflammatory cytokines IFN- and IL-2. Importantly, fluorescence analysis of fibroblast growth factor 2 and tumor cell-induced vessel growth in Matrigel plugs demonstrated marked suppression of angiogenesis only in vaccinated animals. Taken together, this multifunctional DNA vaccine proved effective in protecting against growth and metastases of breast cancer by combining the action of immune effector cells with suppression of tumor angiogenesis. vaccine | tumor | metastases | antiangiogenesis

  4. “Iron-saturated” bovine lactoferrin improves the chemotherapeutic effects of tamoxifen in the treatment of basal-like breast cancer in mice

    Directory of Open Access Journals (Sweden)

    Sun Xueying

    2012-12-01

    Full Text Available Abstract Background Tamoxifen is used in hormone therapy for estrogen-receptor (ER-positive breast cancer, but also has chemopreventative effects against ER-negative breast cancers. This study sought to investigate whether oral iron-saturated bovine lactoferrin (Fe-Lf, a natural product which enhances chemotherapy, could improve the chemotherapeutic effects of tamoxifen in the treatment of ER-negative breast cancers. Methods In a model of breast cancer prevention, female Balb/c mice treated with tamoxifen (5 mg/Kg were fed an Fe-Lf supplemented diet (5 g/Kg diet or the base diet. At week 2, 4T1 mammary carcinoma cells were injected into an inguinal mammary fat pad. In a model of breast cancer treatment, tamoxifen treatment was not started until two weeks following tumor cell injection. Tumor growth, metastasis, body weight, and levels of interleukin 18 (IL-18 and interferon γ (IFN-γ were analyzed. Results Tamoxifen weakly (IC50 ~ 8 μM inhibited the proliferation of 4T1 cells at pharmacological concentrations in vitro. In the tumor prevention study, a Fe-Lf diet in combination with tamoxifen caused a 4 day delay in tumor formation, and significantly inhibited tumor growth and metastasis to the liver and lung by 48, 58, and 66% (all P P  Conclusions The results indicate that Fe-Lf is a potent natural adjuvant capable of augmenting the chemotherapeutic activity of tamoxifen. It could have application in delaying relapse in tamoxifen-treated breast cancer patients who are at risk of developing ER-negative tumors.

  5. SDF-1α mediates wound-promoted tumor growth in a syngeneic orthotopic mouse model of breast cancer.

    Directory of Open Access Journals (Sweden)

    Christina H Stuelten

    Full Text Available Increased growth of residual tumors in the proximity of acute surgical wounds has been reported; however, the mechanisms of wound-promoted tumor growth remain unknown. Here, we used a syngeneic, orthotopic mouse model of breast cancer to study mechanisms of wound-promoted tumor growth. Our results demonstrate that exposure of metastatic mouse breast cancer cells (4T1 to SDF-1α, which is increased in wound fluid, results in increased tumor growth. Both, wounding and exposure of 4T1 cells to SDF-1α not only increased tumor growth, but also tumor cell proliferation rate and stromal collagen deposition. Conversely, systemic inhibition of SDF-1α signaling with the small molecule AMD 3100 abolished the effect of wounding, and decreased cell proliferation, collagen deposition, and neoangiogenesis to the levels observed in control animals. Furthermore, using different mouse strains we could demonstrate that the effect of wounding on tumor growth and SDF-1α levels is host dependent and varies between mouse strains. Our results show that wound-promoted tumor growth is mediated by elevated SDF-1α levels and indicate that the effect of acute wounds on tumor growth depends on the predetermined wound response of the host background and its predetermined wound response.

  6. Breast imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kopans, D.B.; Meyer, J.E.; Sadowsky, N.

    1984-04-12

    The majority of information available today indiates that the most efficient and accurate method of screening women to detect early-stage breast cancer is an aggressive program of patient self-examination, physical examination by well-trained, motivated personnel, and high-quality x-ray mammography. There are two important factors in the implementation of mammographic screening. The first is the availability of facilities to perform high-quality, low-dose mammography, which is directly related to the second factor: the expense to society for support of this large-scale effort. Cost-benefit analysis is beyond the scope of this review. In 1979 Moskowitz and Fox attempted to address this issue, using data from the Breast Cancer Detection Demonstration Project in Cincinnati, but additional analysis is required. The cost for each ''curable'' cancer that is detected must be compared with the psychological, social, and personal losses that accrue, as well as the numerous medical expenses incurred, in a frequently protracted death from breast cancer. All other imaging techniques that have been reviewed should be regarded as adjuncts to rather than replacements for mammographic screening. Ultrasound and computerized tomography are helpful when the physical examination and mammogram are equivocal. Other techniques, such as transillumination, thermography, and magnetic-resonance imaging, should be considered experimental. In patients with clinically evident lesions, x-ray mammography is helpful to evaluate the suspicious area, as well as to ''screen'' the remaining tissue in both breasts and to search for multicentric or bilateral lesions. Mammography is the only imaging technique that has been proved effective for screening.

  7. Breast ultrasound.

    Science.gov (United States)

    Ueno, E

    1996-03-01

    In ultrasound, ultrasonic images are formed by means of echoes among tissues with different acoustic impedance. Acoustic impedance is the product of sound speed and bulk modulus. The bulk modulus expresses the elasticity of an object, and in the human body, the value is increased by conditions such as fibrosis and calcification. The sound speed is usually high in elastic tissues and low in water. In the body, it is lowest in the fatty tissue. Ultrasound echoes are strong on the surface of bones which are hard and have a high sound speed. In organs filled with air such as the lungs, the bulk modulus is low and the sound speed is extremely low at 340 m/s, which produce strong echoes (the sound speed in solid tissues is 1,530 m/s). Human tissue is constructed of units smaller than the ultrasonic beam, and it is necessary to understand back-scattering in order to understand the ultrasonic images of these tissues. When ultrasound passes through tissue, it is absorbed as thermal energy and attenuated. Fiber is a tissue with a high absorption and attenuation rate. When the rate increases, the posterior echoes are attenuated. However, in masses with a high water content such as cysts, the posterior echoes are accentuated. This phenomenon is an important, basic finding for determining the properties of tumors. Breast cancer can be classified into two types: stellate carcinoma and circumscribed carcinoma. Since stellate carcinoma is rich in fiber, the posterior echoes are attenuated or lacking. However, circumscribed carcinoma has a high cellularity and the posterior echoes are accentuated. The same tendency is also seen in benign tumors. In immature fibroadenomas, posterior echoes are accentuated, while in fibroadenomas with hyalinosis, the posterior echoes are attenuated. Therefore, if the fundamentals of this tissue characterization and the histological features are understood, reading of ultrasound becomes easy. Color Doppler has also been developed and has contributed

  8. Advances in Murine Models of Diabetic Nephropathy

    Science.gov (United States)

    Kong, Li-li; Wu, Hao; Cui, Wen-peng; Zhou, Wen-hua; Luo, Ping; Sun, Jing; Yuan, Hang; Miao, Li-ning

    2013-01-01

    Diabetic nephropathy (DN) is one of the microvascular complications of both type 1 and type 2 diabetes, which is also associated with a poor life expectancy of diabetic patients. However, the pathogenesis of DN is still unclear. Thus, it is of great use to establish appropriate animal models of DN for doing research on pathogenesis and developing novel therapeutic strategies. Although a large number of murine models of DN including artificially induced, spontaneous, and genetically engineered (knockout and transgenic) animal models have been developed, none of them develops renal changes sufficiently reflecting those seen in humans. Here we review the identified murine models of DN from the aspects of genetic background, type of diabetes, method of induction, gene deficiency, animal age and gender, kidney histopathology, and phenotypic alterations in the hope of enhancing our comprehension of genetic susceptibility and molecular mechanisms responsible for this disease and providing new clues as to how to choose appropriate animal models of DN. PMID:23844375

  9. Murine Typhus: Clinical and epidemiological aspects

    Directory of Open Access Journals (Sweden)

    Gaspar Peniche Lara

    2012-06-01

    Full Text Available Rickettsia typhi is an intracellular bacteria who causes murine typhus. His importance is reflected in the high frequency founding specific antibodies against R. typhi in several worldwide seroepidemiological studies, the seroprevalence ranging between 3-36%. Natural reservoirs of Rickettsia typhi are rats (some species belonging the Rattus Genus and fleas (Xenopsylla cheopis are his vector. This infection is associated with overcrowding, pollution and poor hygiene. Typically presents fever, headache, rash on trunk and extremities, in some cases may occur organ-specific complications, affecting liver, kidney, lung or brain. Initially the disease is very similar to other diseases, is very common to confuse the murine typhus with Dengue fever, therefore, ignorance of the disease is a factor related to complications or non-specific treatments for the resolution of this infection. This paper presents the most relevant information to consider about the rickettsiosis caused by Rickettsia typhi.

  10. Advances in Murine Models of Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Li-li Kong

    2013-01-01

    Full Text Available Diabetic nephropathy (DN is one of the microvascular complications of both type 1 and type 2 diabetes, which is also associated with a poor life expectancy of diabetic patients. However, the pathogenesis of DN is still unclear. Thus, it is of great use to establish appropriate animal models of DN for doing research on pathogenesis and developing novel therapeutic strategies. Although a large number of murine models of DN including artificially induced, spontaneous, and genetically engineered (knockout and transgenic animal models have been developed, none of them develops renal changes sufficiently reflecting those seen in humans. Here we review the identified murine models of DN from the aspects of genetic background, type of diabetes, method of induction, gene deficiency, animal age and gender, kidney histopathology, and phenotypic alterations in the hope of enhancing our comprehension of genetic susceptibility and molecular mechanisms responsible for this disease and providing new clues as to how to choose appropriate animal models of DN.

  11. Immunodetection of Murine Lymphotoxins in Eukaryotic Cells.

    Science.gov (United States)

    Boitchenko, Veronika E.; Korobko, Vyacheslav G.; Prassolov, Vladimir S.; Kravchenko, Vladimir V.; Kuimov, Alexander N.; Turetskaya, Regina L.; Kuprash, Dmitry V.; Nedospasov, Sergei A.

    2000-10-01

    Lymphotoxins alpha and beta (LTalpha and LTbeta) are members of tumor necrosis factor superfamily. LT heterotrimers exist on the surface of lymphocytes and signal through LTbeta receptor while soluble LTalpha homotrimer can signal through TNF receptors p55 and p75. LT-, as well as TNF-mediated signaling are important for the organogenesis and maintenance of microarchitecture of secondary lymphoid organs in mice and has been implicated in the mechanism of certain inflammatory syndromes in humans. In this study we describe the generation of eukaryotic expression plasmids encoding murine LTalpha and LTbeta genes and a prokaryotic expression construct for murine LTalpha. Using recombinant proteins expressed by these vectors as tools for antisera selection, we produced and characterized several polyclonal antibodies capable of detecting LT proteins in eukaryotic cells.

  12. Breast cancer in men

    Science.gov (United States)

    ... in situ - male; Intraductal carcinoma - male; Inflammatory breast cancer - male; Paget disease of the nipple - male; Breast cancer - male ... The cause of breast cancer in men is not clear. But there are risk factors that make breast cancer more likely in men: Exposure to ...

  13. Breast Cancer -- Male

    Science.gov (United States)

    ... Home > Types of Cancer > Breast Cancer in Men Breast Cancer in Men This is Cancer.Net’s Guide to Breast Cancer in Men. Use the menu below to choose ... social workers, and patient advocates. Cancer.Net Guide Breast Cancer in Men Introduction Statistics Risk Factors and Prevention ...

  14. Co-loaded paclitaxel/rapamycin liposomes: Development, characterization and in vitro and in vivo evaluation for breast cancer therapy

    Science.gov (United States)

    Eloy, Josimar O.; Petrilli, Raquel; Topan, José Fernando; Antonio, Heriton Marcelo Ribeiro; Barcellos, Juliana Palma Abriata; Chesca, Deise L.; Serafini, Luciano Neder; Tiezzi, Daniel G.; Lee, Robert J.; Marchetti, Juliana Maldonado

    2016-01-01

    Paclitaxel and rapamycin have been reported to act synergistically to treat breast cancer. Albeit paclitaxel is available for breast cancer treatment, the most commonly used formulation in the clinic presents side effects, limiting its use. Furthermore, both drugs present pharmacokinetics drawbacks limiting their in vivo efficacy and clinic combination. As an alternative, drug delivery systems, particularly liposomes, emerge as an option for drug combination, able to simultaneously deliver co-loaded drugs with improved therapeutic index. Therefore, the purpose of this study is to develop and characterize a co-loaded paclitaxel and rapamycin liposome and evaluate it for breast cancer efficacy both in vitro and in vivo. Results showed that a SPC/Chol/DSPE-PEG (2000) liposome was able to co-encapsulate paclitaxel and rapamycin with suitable encapsulation efficiency values, nanometric particle size, low polydispersity and neutral zeta potential. Taken together, FTIR and thermal analysis evidenced drug conversion to the more bioavailable molecular and amorphous forms, respectively, for paclitaxel and rapamycin. The pegylated liposome exhibited excellent colloidal stability and was able to retain drugs encapsulated, which were released in a slow and sustained fashion. Liposomes were more cytotoxic to 4T1 breast cancer cell line than the free drugs and drugs acted synergistically, particularly when co-loaded. Finally, in vivo therapeutic evaluation carried out in 4T1-tumor-bearing mice confirmed the in vitro results. The co-loaded paclitaxel/rapamycin pegylated liposome better controlled tumor growth compared to the solution. Therefore, we expect that the formulation developed herein might be a contribution for future studies focusing on the clinical combination of paclitaxel and rapamycin. PMID:26836480

  15. Co-loaded paclitaxel/rapamycin liposomes: Development, characterization and in vitro and in vivo evaluation for breast cancer therapy.

    Science.gov (United States)

    Eloy, Josimar O; Petrilli, Raquel; Topan, José Fernando; Antonio, Heriton Marcelo Ribeiro; Barcellos, Juliana Palma Abriata; Chesca, Deise L; Serafini, Luciano Neder; Tiezzi, Daniel G; Lee, Robert J; Marchetti, Juliana Maldonado

    2016-05-01

    Paclitaxel and rapamycin have been reported to act synergistically to treat breast cancer. Albeit paclitaxel is available for breast cancer treatment, the most commonly used formulation in the clinic presents side effects, limiting its use. Furthermore, both drugs present pharmacokinetics drawbacks limiting their in vivo efficacy and clinic combination. As an alternative, drug delivery systems, particularly liposomes, emerge as an option for drug combination, able to simultaneously deliver co-loaded drugs with improved therapeutic index. Therefore, the purpose of this study is to develop and characterize a co-loaded paclitaxel and rapamycin liposome and evaluate it for breast cancer efficacy both in vitro and in vivo. Results showed that a SPC/Chol/DSPE-PEG (2000) liposome was able to co-encapsulate paclitaxel and rapamycin with suitable encapsulation efficiency values, nanometric particle size, low polydispersity and neutral zeta potential. Taken together, FTIR and thermal analysis evidenced drug conversion to the more bioavailable molecular and amorphous forms, respectively, for paclitaxel and rapamycin. The pegylated liposome exhibited excellent colloidal stability and was able to retain drugs encapsulated, which were released in a slow and sustained fashion. Liposomes were more cytotoxic to 4T1 breast cancer cell line than the free drugs and drugs acted synergistically, particularly when co-loaded. Finally, in vivo therapeutic evaluation carried out in 4T1-tumor-bearing mice confirmed the in vitro results. The co-loaded paclitaxel/rapamycin pegylated liposome better controlled tumor growth compared to the solution. Therefore, we expect that the formulation developed herein might be a contribution for future studies focusing on the clinical combination of paclitaxel and rapamycin.

  16. Cone inputs to murine striate cortex

    Directory of Open Access Journals (Sweden)

    Gouras Peter

    2008-11-01

    Full Text Available Abstract Background We have recorded responses from single neurons in murine visual cortex to determine the effectiveness of the input from the two murine cone photoreceptor mechanisms and whether there is any unique selectivity for cone inputs at this higher region of the visual system that would support the possibility of colour vision in mice. Each eye was stimulated by diffuse light, either 370 (strong stimulus for the ultra-violet (UV cone opsin or 505 nm (exclusively stimulating the middle wavelength sensitive (M cone opsin, obtained from light emitting diodes (LEDs in the presence of a strong adapting light that suppressed the responses of rods. Results Single cells responded to these diffuse stimuli in all areas of striate cortex. Two types of responsive cells were encountered. One type (135/323 – 42% had little to no spontaneous activity and responded at either the on and/or the off phase of the light stimulus with a few impulses often of relatively large amplitude. A second type (166/323 – 51% had spontaneous activity and responded tonically to light stimuli with impulses often of small amplitude. Most of the cells responded similarly to both spectral stimuli. A few (18/323 – 6% responded strongly or exclusively to one or the other spectral stimulus and rarely in a spectrally opponent manner. Conclusion Most cells in murine striate cortex receive excitatory inputs from both UV- and M-cones. A small fraction shows either strong selectivity for one or the other cone mechanism and occasionally cone opponent responses. Cells that could underlie chromatic contrast detection are present but extremely rare in murine striate cortex.

  17. Murine models of human wound healing.

    Science.gov (United States)

    Chen, Jerry S; Longaker, Michael T; Gurtner, Geoffrey C

    2013-01-01

    In vivo wound healing experiments remain the most predictive models for studying human wound healing, allowing an accurate representation of the complete wound healing environment including various cell types, environmental cues, and paracrine interactions. Small animals are economical, easy to maintain, and allow researchers to take advantage of the numerous transgenic strains that have been developed to investigate the specific mechanisms involved in wound healing and regeneration. Here we describe three reproducible murine wound healing models that recapitulate the human wound healing process.

  18. pH-Responsive Wormlike Micelles with Sequential Metastasis Targeting Inhibit Lung Metastasis of Breast Cancer.

    Science.gov (United States)

    He, Xinyu; Yu, Haijun; Bao, Xiaoyue; Cao, Haiqiang; Yin, Qi; Zhang, Zhiwen; Li, Yaping

    2016-02-18

    Cancer metastasis is the main cause for the high mortality in breast cancer patients. Herein, we first report succinobucol-loaded pH-responsive wormlike micelles (PWMs) with sequential targeting capability to inhibit lung metastasis of breast cancer. PWMs can in a first step be delivered specifically to the sites of metastases in the lungs and then enable the intracellular pH-stimulus responsive drug release in cancer cells to improve the anti-metastatic effect. PWMs are identified as nanofibrillar assemblies with a diameter of 19.9 ± 1.9 nm and a length within the 50-200 nm range, and exhibited pH-sensitive drug release behavior in response to acidic intracellular environments. Moreover, PWMs can obviously inhibit the migration and invasion abilities of metastatic 4T1 breast cancer cells, and reduce the expression of the metastasis-associated vascular cell adhesion molecule-1 (VCAM-1) at 400 ng mL(-1) of succinobucol. In particular, PWMs can induce a higher specific accumulation in lung and be specifically delivered to the sites of metastases in lung, thereby leading to an 86.6% inhibition on lung metastasis of breast cancer. Therefore, the use of sequentially targeting PWMs can become an encouraging strategy for specific targeting and effective treatment of cancer metastasis.

  19. Imaging male breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Doyle, S., E-mail: sdoyle2@nhs.net [Primrose Breast Care Unit, Derriford Hospital, Plymouth (United Kingdom); Steel, J.; Porter, G. [Primrose Breast Care Unit, Derriford Hospital, Plymouth (United Kingdom)

    2011-11-15

    Male breast cancer is rare, with some pathological and radiological differences from female breast cancer. There is less familiarity with the imaging appearances of male breast cancer, due to its rarity and the more variable use of preoperative imaging. This review will illustrate the commonest imaging appearances of male breast cancer, with emphasis on differences from female breast cancer and potential pitfalls in diagnosis, based on a 10 year experience in our institution.

  20. Detección de secuencias homologas al Gen Env del virus del tumor mamario murino (MMTV en Cáncer de mama de pacientes argentinas Detection of murine mammary tumor virus (MMTV env gene-like sequences in breast cancer from Argentine patients

    Directory of Open Access Journals (Sweden)

    Stella M. Melana

    2002-08-01

    Full Text Available En los últimos años se ha renovado el interés en la investigación sobre la posible etiología viral del cáncer de mama humano. En publicaciones previas se ha demostrado la presencia de secuencias homólogas al gen env del virus del Tumor Mamario Murino (MMTV en alrededor del 38% de cánceres de mama de mujeres procedentes de Estados Unidos e Italia; estas secuencias están generalmente ausentes en otros tumores y en tejido mamario normal. En el presente trabajo se analizó la presencia de una secuencia de 250 pb similar a la del gen env de MMTV en biopsias de pacientes argentinas con cáncer de mama. Se detectó este fragmento retroviral en el 31% (23/74 de los tumores analizados, mientras que sólo se obtuvo un caso positivo en tejido de mama normal y ninguno en fibroadenomas. En 46 pacientes con cáncer se analizaron células mononucleares de sangre periférica, detectando la secuencia en el 17% (2/12 de las pacientes portadoras de tumores env positivos y en el 3% (1/34 de aquéllas cuyos tumores eran env negativos. Los datos de Argentina son similares a los obtenidos en Estados Unidos e Italia donde la incidencia de cáncer de mama es también semejante. Estos resultados apoyarían la hipótesis de un probable agente viral implicado en la génesis de esta neoplasia y alientan los estudios en marcha.In the last years research on the possible viral etiology of human breast cancer has been revised. Previous studies have demonstrated the presence of a Mouse Mammary Tumor Virus (MMTV env gene-like sequence in about 38% of breast cancers from American and Italian women; these sequences are generally absent in other tumors and in normal mammary tissue. In the present study we have analyzed the presence of a 250-bp sequence of the MMTV env gene in breast cancer biopsies from Argentine patients. The retroviral fragment was present in 31% (23/74 of the tumors, only in one normal mammary tissue and in none of the fibroadenomas analized. Peripheral

  1. Associated expressions of FGFR-2 and FGFR-3: from mouse mammary gland physiology to human breast cancer.

    Science.gov (United States)

    Cerliani, Juan P; Vanzulli, Silvia I; Piñero, Cecilia Pérez; Bottino, María C; Sahores, Ana; Nuñez, Myriam; Varchetta, Romina; Martins, Rubén; Zeitlin, Eduardo; Hewitt, Stephen M; Molinolo, Alfredo A; Lanari, Claudia; Lamb, Caroline A

    2012-06-01

    Fibroblast growth factor receptors (FGFRs) are tyrosine kinase receptors which have been implicated in breast cancer. The aim of this study was to evaluate FGFR-1, -2, -3, and -4 protein expressions in normal murine mammary gland development, and in murine and human breast carcinomas. Using immunohistochemistry and Western blot, we report a hormonal regulation of FGFR during postnatal mammary gland development. Progestin treatment of adult virgin mammary glands resulted in changes in localization of FGFR-3 from the cytoplasm to the nucleus, while treatment with 17-β-estradiol induced changes in the expressions and/or localizations of FGFR-2 and -3. In murine mammary carcinomas showing different degrees of hormone dependence, we found progestin-induced increased expressions, mainly of FGFR-2 and -3. These receptors were constitutively activated in hormone-independent variants. We studied three luminal human breast cancer cell lines growing as xenografts, which particularly expressed FGFR-2 and -3, suggesting a correlation between hormonal status and FGFR expression. Most importantly, in breast cancer samples from 58 patients, we found a strong association (P FGFR-2 and -3 expressions and a weaker correlation of each receptor with estrogen receptor expression. FGFR-4 correlated with c-erbB2 over expression. We conclude that FGFR-2 and -3 may be mechanistically linked and can be potential targets for treatment of estrogen receptor-positive breast cancer patients.

  2. In vivo magnetic resonance imaging investigating the development of experimental brain metastases due to triple negative breast cancer.

    Science.gov (United States)

    Hamilton, Amanda M; Foster, Paula J

    2017-02-01

    Triple negative breast cancer (TNBC), when associated with poor outcome, is aggressive in nature with a high incidence of brain metastasis and the shortest median overall patient survival after brain metastasis development compared to all other breast cancer subtypes. As therapies that control primary cancer and extracranial metastatic sites improve, the incidence of brain metastases is increasing and the management of patients with breast cancer brain metastases continues to be a significant clinical challenge. Mouse models have been developed to permit in depth evaluation of breast cancer metastasis to the brain. In this study, we compare the efficiency and metastatic potential of two experimental mouse models of TNBC. Longitudinal MRI analysis and end point histology were used to quantify initial cell arrest as well as the number and volume of metastases that developed in mouse brain over time. We showed significant differences in MRI appearance, tumor progression and model efficiency between the syngeneic 4T1-BR5 model and the xenogeneic 231-BR model. Since TNBC does not respond to many standard breast cancer treatments and TNBC brain metastases lack effective targeted therapies, these preclinical TNBC models represent invaluable tools for the assessment of novel systemic therapeutic approaches. Further pursuits of therapeutics designed to bypass the blood tumor barrier and permit access to the brain parenchyma and metastatic cells within the brain will be paramount in the fight to control and treat lethal metastatic cancer.

  3. Furanodiene enhances the anti-cancer effects of doxorubicin on ERα-negative breast cancer cells in vitro.

    Science.gov (United States)

    Zhong, Zhang-Feng; Qiang, Wen-An; Wang, Chun-Ming; Tan, Wen; Wang, Yi-Tao

    2016-03-05

    Furanodiene is a natural product isolated from Rhizoma curcumae, and exhibits broad-spectrum anti-cancer activities in vitro and in vivo. Our previous study proved that furanodiene could increase growth inhibition of steroidal agent in ERα-positive breast cancer cells, but whether furanodiene can influence ER status is not clear. In this study, we confirmed that furanodiene down-regulated the ERα protein expression level and inhibited E2-induced estrogen response element (ERE)-driven reporter plasmid activity in ERα-positive MCF-7 cells. Actually, ERα-knockdown cells were more sensitive than ERα positive cells to furanodiene on the cytotoxicity effect. So the anti-cancer effects of furanodiene and non-steroidal agent in breast cancer cells still requires further investigation. Our results showed that furanodiene exposure could enhance growth inhibitory effects of doxorubicin in ERα-negative MDA-MB-231 cells and ERα-low expression 4T1 cells. However, furanodiene did not increase the cytotoxicity of doxorubicin in ERα-positive breast cancer cells, non-tumorigenic breast epithelial cells, macrophage cells, hepatocytes cells, pheochromocytoma cells and cardiac myoblasts cells. Furanodiene enhances the anti-cancer effects of doxorubicin in ERα-negative breast cancer cells through suppressing cell viability via inducing apoptosis in mitochondria-caspases-dependent and reactive oxygen species-independent manners. These results indicate that furanodiene may be a promising and safety natural agent for cancer adjuvant therapy in the future.

  4. Should I Have Breast Reconstruction?

    Science.gov (United States)

    ... Reconstruction Surgery Breast Cancer Breast Reconstruction Surgery Should I Get Breast Reconstruction Surgery? Women who have surgery ... It usually responds well to treatment. What if I choose not to have breast reconstruction? Many women ...

  5. Risks of Breast Cancer Screening

    Science.gov (United States)

    ... of dying from breast cancer. MRI (magnetic resonance imaging) in women with a high risk of breast ... a mammogram , the breast is placed between 2 plates that are pressed together. Pressing the breast helps ...

  6. Ultrasound-Guided Breast Biopsy

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Ultrasound-Guided Breast Biopsy An ultrasound-guided breast biopsy ... limitations of Ultrasound-Guided Breast Biopsy? What is Ultrasound-Guided Breast Biopsy? Lumps or abnormalities in the ...

  7. An MMP13-selective inhibitor delays primary tumor growth and the onset of tumor-associated osteolytic lesions in experimental models of breast cancer.

    Directory of Open Access Journals (Sweden)

    Manisha Shah

    Full Text Available We investigated the effects of the matrix metalloproteinase 13 (MMP13-selective inhibitor, 5-(4-{4-[4-(4-fluorophenyl-1,3-oxazol-2-yl]phenoxy}phenoxy-5-(2-methoxyethyl pyrimidine-2,4,6(1H,3H,5H-trione (Cmpd-1, on the primary tumor growth and breast cancer-associated bone remodeling using xenograft and syngeneic mouse models. We used human breast cancer MDA-MB-231 cells inoculated into the mammary fat pad and left ventricle of BALB/c Nu/Nu mice, respectively, and spontaneously metastasizing 4T1.2-Luc mouse mammary cells inoculated into mammary fat pad of BALB/c mice. In a prevention setting, treatment with Cmpd-1 markedly delayed the growth of primary tumors in both models, and reduced the onset and severity of osteolytic lesions in the MDA-MB-231 intracardiac model. Intervention treatment with Cmpd-1 on established MDA-MB-231 primary tumors also significantly inhibited subsequent growth. In contrast, no effects of Cmpd-1 were observed on soft organ metastatic burden following intracardiac or mammary fat pad inoculations of MDA-MB-231 and 4T1.2-Luc cells respectively. MMP13 immunostaining of clinical primary breast tumors and experimental mice tumors revealed intra-tumoral and stromal expression in most tumors, and vasculature expression in all. MMP13 was also detected in osteoblasts in clinical samples of breast-to-bone metastases. The data suggest that MMP13-selective inhibitors, which lack musculoskeletal side effects, may have therapeutic potential both in primary breast cancer and cancer-induced bone osteolysis.

  8. Breast metastases from rectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    LI Jia; FANG Yu; LI Ang; LI Fei

    2011-01-01

    Metastases to the breast from extramammary neoplasms are very rare, constituting 2.7% of all malignant breast tumours. The most common primary tumor metastatic to the breast is primary breast cancer. Rectal cancer metastasizing to the breast is extremely rare. We report a case of aggressive rectal carcinoma with metastasis to the breast.

  9. Liposomal Nanoparticles Carrying anti-IL6R Antibody to the Tumour Microenvironment Inhibit Metastasis in Two Molecular Subtypes of Breast Cancer Mouse Models

    Science.gov (United States)

    Guo, Chunlei; Chen, Yanan; Gao, Wenjuan; Chang, Antao; Ye, Yujie; Shen, Wenzhi; Luo, Yunping; Yang, Shengyong; Sun, Peiqing; Xiang, Rong; Li, Na

    2017-01-01

    Tumour microenvironment (TME) contributes significantly towards potentiating the stemness and metastasis properties of cancer cells. IL6-Stat3 is one of the important cell signaling pathways in mediating the communication between tumour and immune cells. Here, we have systematically developed a novel anti-CD44 antibody-mediated liposomal nanoparticle delivery system loaded with anti-IL6R antibody, which could specifically target the TME of CD44+ breast cancer cells in different mouse models for triple negative and luminal breast cancer. This nanoparticle had an enhanced and specific tumour targeting efficacy with dramatic anti-tumour metastasis effects in syngeneic BALB/c mice bearing 4T1 cells as was in the syngeneic MMTV-PyMT mice. It inhibited IL6R-Stat3 signaling and moderated the TME, characterized by the reduced expression of genes encoding Stat3, Sox2, VEGFA, MMP-9 and CD206 in the breast tissues. Furthermore, this nanoparticle reduced the subgroups of Sox2+ and CD206+ cells in the lung metastatic foci, demonstrating its inhibitory effect on the lung metastatic niche for breast cancer stem cells. Taken together, the CD44 targeted liposomal nanoparticles encapsulating anti-IL6R antibody achieved a significant effect to inhibit the metastasis of breast cancer in different molecular subtypes of breast cancer mouse models. Our results shed light on the application of nanoparticle mediated cancer immune-therapy through targeting TME. PMID:28255366

  10. Breast Imaging Artifacts.

    Science.gov (United States)

    Odle, Teresa G

    2015-01-01

    Artifacts appear on breast images for a number of reasons. Radiologic technologists play an important role in identifying artifacts that can help or hinder breast cancer diagnosis and in minimizing artifacts that degrade image quality. This article describes various artifacts that occur in breast imaging, along with their causes. The article focuses on artifacts in mammography, with a heavy emphasis on digital mammography, and on magnetic resonance imaging of the breast. Artifacts in ultrasonography of the breast, digital breast tomosynthesis, and positron emission mammography also are discussed.

  11. Accelerated partial breast irradiation

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    @@ Whole breast radiotherapy afier tumor lumpectomy is based on the premise that that the breast cancer recurrence rate is reduced through the elimination of residual cancer foci in the remaining tissue immediately adjacent to the lumpectomy site and occult multicentric areas of in situ or infiltrating cancer in remote areas of the breast. The relevance of remote foci to ipsilateral breast failure rates after breast conserving treatment is debatable, because 65%~100% of recurrences develop in the same quadrant as the initial tumor. This has led several investigators to question whether radiotherapy must be administered to the entire breast.

  12. Pten in the Breast Tumor Microenvironment: Modeling Tumor-Stroma Co-Evolution

    Science.gov (United States)

    Wallace, Julie A.; Li, Fu; Leone, Gustavo; Ostrowski, Michael C.

    2010-01-01

    Solid human tumors and their surrounding microenvironment are hypothesized to co-evolve in a manner that promotes tumor growth, invasiveness and spread. Mouse models of cancer have focused on genetic changes in the epithelial tumor cells and therefore have not robustly tested this hypothesis. We have recently developed a murine breast cancer model that ablates the PTEN tumor suppressor pathway in stromal fibroblasts. Remarkably, the model resembles human breast tumors both at morphologic and molecular levels. We propose that such models reflect subtypes of tumor-stromal co-evolution relevant to human breast cancer, and will therefore be useful in defining the mechanisms that underpin tumor-stroma crosstalk. Additionally, these models should also aid in molecularly classifying human breast tumors based on both the microenvironment subtypes they contain as well as on the tumor subtype. PMID:21303970

  13. Breast cancer screening in Korean woman with dense breast tissue

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Hee Jung [Dept. of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Ko, Eun Sook [Dept. of Radiology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul (Korea, Republic of); Yi, Ann [Dept. of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul (Korea, Republic of)

    2015-11-15

    Asian women, including Korean, have a relatively higher incidence of dense breast tissue, compared with western women. Dense breast tissue has a lower sensitivity for the detection of breast cancer and a higher relative risk for breast cancer, compared with fatty breast tissue. Thus, there were limitations in the mammographic screening for women with dense breast tissue, and many studies for the supplemental screening methods. This review included appropriate screening methods for Korean women with dense breasts. We also reviewed the application and limitation of supplemental screening methods, including breast ultrasound, digital breast tomosynthesis, and breast magnetic resonance imaging; and furthermore investigated the guidelines, as well as the study results.

  14. Irradiation Design for an Experimental Murine Model

    Science.gov (United States)

    Ballesteros-Zebadúa, P.; Lárraga-Gutierrez, J. M.; García-Garduño, O. A.; Rubio-Osornio, M. C.; Custodio-Ramírez, V.; Moreno-Jimenez, S.; Suarez-Campos, J. E.; Paz, C.; Celis, M. A.

    2010-12-01

    In radiotherapy and stereotactic radiosurgery, small animal experimental models are frequently used, since there are still a lot of unsolved questions about the biological and biochemical effects of ionizing radiation. This work presents a method for small-animal brain radiotherapy compatible with a dedicated 6MV Linac. This rodent model is focused on the research of the inflammatory effects produced by ionizing radiation in the brain. In this work comparisons between Pencil Beam and Monte Carlo techniques, were used in order to evaluate accuracy of the calculated dose using a commercial planning system. Challenges in this murine model are discussed.

  15. Efficacy of Ambruticin Analogs in a Murine Model of Coccidioidomycosis

    OpenAIRE

    Shubitz, Lisa F.; Galgiani, John N.; Tian, Zong-Qiang; Zhong, Ziyang; Timmermans, Pieter; Katz, Leonard

    2006-01-01

    Ambruticin S, an antifungal cyclopropyl-pyran acid, showed curative effects against murine coccidioidal infection. Two analogs of this compound with greater in vitro potency were tested against lethal murine Coccidioides infection. Both improved the survival of mice over that of controls; one resulted in near-sterilization of infection.

  16. Murine erythrocytes contain high levels of lysophospholipase activity

    NARCIS (Netherlands)

    Kamp, J.A.F. op den; Roelofsen, B.; Sanderink, G.; Middelkoop, E.; Hamer, R.

    1984-01-01

    Murine erythrocytes were found to be unique in the high levels of lysophospholipase activity in the cytosol of these cells. The specific activity of the enzyme in the cytosol of the murine cells is 10-times higher than in the cytosol of rabbit erythrocytes and approximately three orders of magnitude

  17. Identification of Putative Metastasis Suppressor MicroRNA in Human Breast Cancer

    Science.gov (United States)

    2009-11-01

    Levels Correlate Inversely with Metastatic Ability in Breast Cell Lines (A) RT-PCR for miR-31 in seven human breast cell lines. 5S rRNA was a loading...control. NTC, no template control. n = 3. (B) miR-31 RT-PCR in eight murine mammary cell lines. 5S rRNA was a loading control. n = 3. (C) In situ...nondiseased individuals; metastasis-positive and -free: tumors of the indicated distant metastasis outcome. 5S rRNA was a loading control. n = 4 (normal

  18. Recovery of extracellular vesicles from human breast milk is influenced by sample collection and vesicle isolation procedures

    Science.gov (United States)

    Zonneveld, Marijke I.; Brisson, Alain R.; van Herwijnen, Martijn J. C.; Tan, Sisareuth; van de Lest, Chris H. A.; Redegeld, Frank A.; Garssen, Johan; Wauben, Marca H. M.; Nolte-'t Hoen, Esther N. M.

    2014-01-01

    Extracellular vesicles (EV) in breast milk carry immune relevant proteins and could play an important role in the instruction of the neonatal immune system. To further analyze these EV and to elucidate their function it is important that native populations of EV can be recovered from (stored) breast milk samples in a reproducible fashion. However, the impact of isolation and storage procedures on recovery of breast milk EV has remained underexposed. Here, we aimed to define parameters important for EV recovery from fresh and stored breast milk. To compare various protocols across different donors, breast milk was spiked with a well-defined murine EV population. We found that centrifugation of EV down into density gradients largely improved density-based separation and isolation of EV, compared to floatation up into gradients after high-force pelleting of EV. Using cryo-electron microscopy, we identified different subpopulations of human breast milk EV and a not previously described population of lipid tubules. Additionally, the impact of cold storage on breast milk EV was investigated. We determined that storing unprocessed breast milk at −80°C or 4°C caused death of cells present in breast milk, leading to contamination of the breast milk EV population with storage-induced EV. Here, an alternative method is proposed to store breast milk samples for EV analysis at later time points. The proposed adaptations to the breast milk storage and EV isolation procedures can be applied for EV-based biomarker profiling of breast milk and functional analysis of the role of breast milk EV in the development of the neonatal immune system. PMID:25206958

  19. Recovery of extracellular vesicles from human breast milk is influenced by sample collection and vesicle isolation procedures.

    Science.gov (United States)

    Zonneveld, Marijke I; Brisson, Alain R; van Herwijnen, Martijn J C; Tan, Sisareuth; van de Lest, Chris H A; Redegeld, Frank A; Garssen, Johan; Wauben, Marca H M; Nolte-'t Hoen, Esther N M

    2014-01-01

    Extracellular vesicles (EV) in breast milk carry immune relevant proteins and could play an important role in the instruction of the neonatal immune system. To further analyze these EV and to elucidate their function it is important that native populations of EV can be recovered from (stored) breast milk samples in a reproducible fashion. However, the impact of isolation and storage procedures on recovery of breast milk EV has remained underexposed. Here, we aimed to define parameters important for EV recovery from fresh and stored breast milk. To compare various protocols across different donors, breast milk was spiked with a well-defined murine EV population. We found that centrifugation of EV down into density gradients largely improved density-based separation and isolation of EV, compared to floatation up into gradients after high-force pelleting of EV. Using cryo-electron microscopy, we identified different subpopulations of human breast milk EV and a not previously described population of lipid tubules. Additionally, the impact of cold storage on breast milk EV was investigated. We determined that storing unprocessed breast milk at -80°C or 4°C caused death of cells present in breast milk, leading to contamination of the breast milk EV population with storage-induced EV. Here, an alternative method is proposed to store breast milk samples for EV analysis at later time points. The proposed adaptations to the breast milk storage and EV isolation procedures can be applied for EV-based biomarker profiling of breast milk and functional analysis of the role of breast milk EV in the development of the neonatal immune system.

  20. Recovery of extracellular vesicles from human breast milk is influenced by sample collection and vesicle isolation procedures

    Directory of Open Access Journals (Sweden)

    Marijke I. Zonneveld

    2014-08-01

    Full Text Available Extracellular vesicles (EV in breast milk carry immune relevant proteins and could play an important role in the instruction of the neonatal immune system. To further analyze these EV and to elucidate their function it is important that native populations of EV can be recovered from (stored breast milk samples in a reproducible fashion. However, the impact of isolation and storage procedures on recovery of breast milk EV has remained underexposed. Here, we aimed to define parameters important for EV recovery from fresh and stored breast milk. To compare various protocols across different donors, breast milk was spiked with a well-defined murine EV population. We found that centrifugation of EV down into density gradients largely improved density-based separation and isolation of EV, compared to floatation up into gradients after high-force pelleting of EV. Using cryo-electron microscopy, we identified different subpopulations of human breast milk EV and a not previously described population of lipid tubules. Additionally, the impact of cold storage on breast milk EV was investigated. We determined that storing unprocessed breast milk at −80°C or 4°C caused death of cells present in breast milk, leading to contamination of the breast milk EV population with storage-induced EV. Here, an alternative method is proposed to store breast milk samples for EV analysis at later time points. The proposed adaptations to the breast milk storage and EV isolation procedures can be applied for EV-based biomarker profiling of breast milk and functional analysis of the role of breast milk EV in the development of the neonatal immune system.

  1. [Immediate breast reconstruction for breast cancer].

    Science.gov (United States)

    Yamamoto, Daigo; Tanaka, Yoshihito; Tsubota, Yu; Sueoka, Noriko; Endo, Kayoko; Ogura, Tsunetaka; Nagumo, Yoshinori; Kwon, A-Hon

    2014-11-01

    We performed immediate breast reconstruction after nipple-sparing mastectomy or skin-sparing mastectomy and evaluated the reconstruction procedure, cosmesis, and complications. Among the 30 patients included in the study, 6 received latissimus dorsi flaps, 1 received a transverse rectus abdominis myocutaneous flap, 7 received deep inferior epigastric perforator flaps, 1 received an implant, and 15 received tissue expanders. In addition, the results were excellent in 25 patients, good in 3 patients, and poor in 2 patients. As the number of patients with breast cancer is increasing, the demand for breast reconstruction will increase. Therefore, it is essential to choose an appropriate method of breast reconstruction for each case.

  2. Influence of the Tumor Microenvironment on Genomic Changes Conferring Chemoresistance in Breast Cancer

    Science.gov (United States)

    2013-04-01

    addition, I generated multiple fluorescent labeling technique and a transgenic mouse that would be useful to examine heterogeneous primary tumor cells in...tumor cells to examine tumor hypoxia, I validated endogenous expression of Hif1α in murine breast cancer cells that ara available at our laboratory...This approach was expected to be an effective way to distinguish individual primary tumor cells from heterogeneous population if combined with

  3. Stereotactic Image-Guided Navigation During Breast Reconstruction in Patients With Breast Cancer

    Science.gov (United States)

    2017-04-12

    Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  4. Breast radiation - discharge

    Science.gov (United States)

    Radiation - breast - discharge ... away around 4 to 6 weeks after the radiation treatment is over. You may notice changes in ... breast looks or feels (if you are getting radiation after a lumpectomy). These changes include: Soreness or ...

  5. Learning about Breast Cancer

    Science.gov (United States)

    ... for the genetic terms used on this page Learning About Breast Cancer What do we know about ... for a small fraction of breast cancers. In Learning About the BRCAX Study , researchers discuss a recent ...

  6. Breast milk jaundice

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000995.htm Breast milk jaundice To use the sharing features on this ... otherwise healthy, the condition may be called "breast milk jaundice." Causes Bilirubin is a yellow pigment that ...

  7. Breastfeeding and Breast Milk

    Science.gov (United States)

    ... Clinical Trials Resources and Publications Breastfeeding and Breast Milk: Condition Information Skip sharing on social media links Share this: Page Content Breastfeeding and Breast Milk: Condition Information​ ​​Breastfeeding, also called nursing, is the ...

  8. Cosmetic breast surgery - discharge

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000273.htm Cosmetic breast surgery - discharge To use the sharing features on this page, please enable JavaScript. You had cosmetic breast surgery to change the size or shape ...

  9. Breast cancer staging

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000911.htm Breast cancer staging To use the sharing features on this ... Once your health care team knows you have breast cancer , they will do more tests to stage it. ...

  10. Breast Cancer in Men

    Science.gov (United States)

    ... Older age • B RCA2 gene mutation • F amily history of breast cancer • Gynecomastia (enlargement of the breast tissue) • Klinefelter’s syndrome (a genetic condition related to high levels ...

  11. Posttraumatic Chondrocyte Apoptosis in the Murine Xiphoid

    Science.gov (United States)

    Davis, Christopher G.; Eisner, Eric; McGlynn, Margaret; Shelton, John M.; Richardson, James

    2013-01-01

    Objective. To demonstrate posttraumatic chondrocyte apoptosis in the murine xiphoid after a crush-type injury and to ultimately determine the pathway (i.e., intrinsic or extrinsic) by which chondrocytes undergo apoptosis in response to mechanical injury. Design. The xiphoids of adult female wild-type mice were injured with the use of a modified Kelly clamp. Postinjury xiphoid cartilage was analyzed via 3 well-described independent means of assessing apoptosis in chondrocytes: hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and activated caspase-3 staining. Results. Injured specimens contained many chondrocytes with evidence of apoptosis, which is characterized by cell shrinkage, chromatin condensation, nuclear fragmentation, and the liberation of apoptotic bodies. There was a statistically significant increase in the number of chondrocytes undergoing apoptosis in the injured specimens as compared with the uninjured specimens. Conclusions. Chondrocytes can be stimulated to undergo apoptosis as a result of mechanical injury. These experiments involving predominantly cartilaginous murine xiphoid in vivo establish a baseline for future investigations that employ the genetic and therapeutic modulation of chondrocyte apoptosis in response to mechanical injury. PMID:26069679

  12. Murine Typhus: Clinical and epidemiological aspects

    Directory of Open Access Journals (Sweden)

    Gaspar Peniche Lara

    2012-06-01

    Full Text Available 14.00 Normal 0 21 false false false ES-CO X-NONE X-NONE Rickettsia typhi is an intracellular bacteria who causes murine typhus. His importance is reflected in the high frequency founding specific antibodies against R. typhi in several worldwide seroepidemiological studies, the seroprevalence ranging between 3-36%. Natural reservoirs of Rickettsia typhi are rats (some species belonging the Rattus Genus and fleas (Xenopsylla cheopis are his vector. This infection is associated with overcrowding, pollution and poor hygiene. Typically presents fever, headache, rash on trunk and extremities, in some cases may occur organ-specific complications, affecting liver, kidney, lung or brain. Initially the disease is very similar to other diseases, is very common to confuse the murine typhus with Dengue fever, therefore, ignorance of the disease is a factor related to complications or non-specific treatments for the resolution of this infection. This paper presents the most relevant information to consider about the rickettsiosis caused by Rickettsia typhi.

  13. Splenectomy normalizes hematocrit in murine polycythemia vera.

    Directory of Open Access Journals (Sweden)

    Jan-Rung Mo

    Full Text Available Splenic enlargement (splenomegaly develops in numerous disease states, although a specific pathogenic role for the spleen has rarely been described. In polycythemia vera (PV, an activating mutation in Janus kinase 2 (JAK2(V617 induces splenomegaly and an increase in hematocrit. Splenectomy is sparingly performed in patients with PV, however, due to surgical complications. Thus, the role of the spleen in the pathogenesis of human PV remains unknown. We specifically tested the role of the spleen in the pathogenesis of PV by performing either sham (SH or splenectomy (SPL surgeries in a murine model of JAK2(V617F-driven PV. Compared to SH-operated mice, which rapidly develop high hematocrits after JAK2(V617F transplantation, SPL mice completely fail to develop this phenotype. Disease burden (JAK2(V617 is equivalent in the bone marrow of SH and SPL mice, however, and both groups develop fibrosis and osteosclerosis. If SPL is performed after PV is established, hematocrit rapidly declines to normal even though myelofibrosis and osteosclerosis again develop independently in the bone marrow. In contrast, SPL only blunts hematocrit elevation in secondary, erythropoietin-induced polycythemia. We conclude that the spleen is required for an elevated hematocrit in murine, JAK2(V617F-driven PV, and propose that this phenotype of PV may require a specific interaction between mutant cells and the spleen.

  14. Thermal resistance in a spontaneous murine tumour.

    Science.gov (United States)

    Maher, J; Urano, M; Rice, L; Suit, H D

    1981-12-01

    Resistance to subsequent hyperthermia as a result of prior heating was investigated using a spontaneous murine tumour implanted into the feet of C3H/Sed mice. Tumours were treated by immersing the tumour-bearing foot into a constant-temperature hot water bath set at 45.5 degrees C and were given single and split doses of heat. Response was assessed using a tumour-growth time assay. Three aspects of thermally-induced resistance were particularly considered: the time course of development and decay; the importance of the magnitude of the priming dose and the influence of the size of the tumour at the time of treatment. Substantial resistance was induced in this tumour by short priming doses at 45.5 degrees C, rising rapidly 1-2 days after the first treatment and then starting to decay. There was no significant difference in the kinetics of thermal resistance induced in tumours treated at 4mm and those treated at 8 mm in size, although the large tumours were more sensitive to single doses of heat. Increasing the magnitude of the priming dose of heat resulted in an increase in the magnitude of resistance to the second dose. The results of this study are compared with results of similar studies in this and other laboratories using murine normal tissues and cells in culture. Possible clinical implications are considered.

  15. Benzaldehyde suppresses murine allergic asthma and rhinitis.

    Science.gov (United States)

    Jang, Tae Young; Park, Chang-Shin; Kim, Kyu-Sung; Heo, Min-Jeong; Kim, Young Hyo

    2014-10-01

    To evaluate the antiallergic effects of oral benzaldehyde in a murine model of allergic asthma and rhinitis, we divided 20 female BALB/c mice aged 8-10 weeks into nonallergic (intraperitoneally sensitized and intranasally challenged to normal saline), allergic (intraperitoneally sensitized and intranasally challenged to ovalbumin), and 200- and 400-mg/kg benzaldehyde (allergic but treated) groups. The number of nose-scratching events in 10 min, levels of total and ovalbumin-specific IgE in serum, differential counts of inflammatory cells in bronchoalveolar lavage (BAL) fluid, titers of Th2 cytokines (IL-4, IL-5, IL-13) in BAL fluid, histopathologic findings of lung and nasal tissues, and expressions of proteins involved in apoptosis (Bcl-2, Bax, caspase-3), inflammation (COX-2), antioxidation (extracellular SOD, HO-1), and hypoxia (HIF-1α, VEGF) in lung tissue were evaluated. The treated mice had significantly fewer nose-scratching events, less inflammatory cell infiltration in lung and nasal tissues, and lower HIF-1α and VEGF expressions in lung tissue than the allergic group. The number of eosinophils and neutrophils and Th2 cytokine titers in BAL fluid significantly decreased after the treatment (Pbenzaldehyde exerts antiallergic effects in murine allergic asthma and rhinitis, possibly through inhibition of HIF-1α and VEGF.

  16. Breast Self- Examination Contradiction

    Directory of Open Access Journals (Sweden)

    Ayla Akkas Gursoy

    2008-06-01

    Full Text Available Breast cancer is very important health problem among women in the World and Turkey. Although treatment chance is very rising and survival is getting longer thanks to early diagnosis in breast cancer. Some discussion is making related to breast self examination which is one of the early detection methods in recent years. This article consider the discussions about breast self examination under the historical development light. [TAF Prev Med Bull 2008; 7(3.000: 257-260

  17. Breast Cancer and Infertility

    OpenAIRE

    2015-01-01

    Breast cancer is the most common malignancy among women and may accompany infertility. The relationship between infertility treatment and breast cancer has not yet been proven. However, estrogen exposure is well known to cause breast cancer. Recent advances in treatment options have provided young patients with breast cancer a chance of being mother [Archives Medical Review Journal 2015; 24(3.000): 317-323

  18. A novel combination treatment for breast cancer cells involving BAPTA-AM and proteasome inhibitor bortezomib

    Science.gov (United States)

    YERLIKAYA, AZMI; ERDOĞAN, ELIF; OKUR, EMRAH; YERLIKAYA, ŞERIFE; SAVRAN, BIRCAN

    2016-01-01

    Glucose-regulated protein 78 kDa/binding immunoglobulin protein (GRP78/BIP) is a well-known endoplasmic reticulum (ER) chaperone protein regulating ER stress by facilitating protein folding, assembly and Ca2+ binding. GRP78 is also a member of the heat shock protein 70 gene family and induces tumor cell survival and resistance to chemotherapeutics. Bortezomib is a highly specific 26S proteasome inhibitor that has been approved as treatment for patients with multiple myeloma. The present study first examined the dose- and time-dependent effects of bortezomib on GRP78 expression levels in the highly metastatic mouse breast cancer 4T1 cell line using western blot analysis. The analysis results revealed that GRP78 levels were significantly increased by bortezomib at a dose as low as 10 nM. Time-dependent experiments indicated that the accumulation of GRP78 was initiated after a 24 h incubation period following the addition of 10 nM bortezomib. Subsequently, the present study determined the half maximal inhibitory concentration of intracellular calcium chelator BAPTA-AM (13.6 µM) on 4T1 cells. The combination effect of BAPTA-AM and bortezomib on the 4T1 cells was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and WST-1 assays and an iCELLigence system. The results revealed that the combination of 10 nM bortezomib + 5 µM BAPTA-AM is more cytotoxic compared with monotherapies, including 10 nM bortezomib, 1 µM BAPTA-AM and 5 µM BAPTA-AM. In addition, the present results revealed that bortezomib + BAPTA-AM combination causes cell death through the induction of apoptosis. The present results also revealed that bortezomib + BAPTA-AM combination-induced apoptosis is associated with a clear increase in the phosphorylation of stress-activated protein kinase/Jun amino-terminal kinase SAPK/JNK. Overall, the present results suggest that bortezomib and BAPTA-AM combination therapy may be a novel therapeutic strategy for breast cancer treatment

  19. Chicken Breast Paste

    Institute of Scientific and Technical Information of China (English)

    1994-01-01

    Ingredients: 50 grams of chicken breast, 150 grams of egg white, ham, cucumber and water chestnuts, 50 grams of starch, 50 grams of oil, salt and MSG. Directions: 1. Chop up the chicken breast and water chestnuts. Mix with egg white and starch into chicken breast paste. 2. Heat the oil for a moment and then place chicken paste in pot.

  20. Breast Cancer (For Kids)

    Science.gov (United States)

    ... With Breast Cancer Breast Cancer Prevention en español Cáncer de mama You may have heard about special events, like walks or races, to raise money for breast cancer research. Or maybe you've seen people wear ...

  1. Breast sarcomas. Literature review

    Directory of Open Access Journals (Sweden)

    D. A. Ryabchikov

    2014-01-01

    Full Text Available The article presents an overview of the literature about breast sarcomas (nonepithelial malignances. Primary sarcomas are extremely rare, with less than 1 % of all malignant tumors of the breast. Breast carcinomas cause an increased interest of the scientists due to their unique clinical and pathological features and unpredictable prognosis.

  2. Breast cancer awareness

    OpenAIRE

    2012-01-01

    The incidence of breast cancer is rising among women in many European countries, affecting up to 1 in 16 women and has become the most common cause of cancer in European women. In Malta breast cancer is the commonest oncological cause of death in females. In fact 5.2% of all deaths in females in 2010 was from breast cancer.

  3. Tubercular breast abscess

    Directory of Open Access Journals (Sweden)

    Pradeep S Jadhav

    2013-01-01

    Full Text Available Tubercular breast abscess is a rare clinical entity and affects women from mainly the Indian subcontinent. It often mimics breast carcinoma and pyogenic breast abscess clinically. Routine laboratory investigations are not helpful in the diagnosis. Fine needle aspiration cytology (FNAC or biopsy is essential for diagnosis, and tuberculous culture when positive may be very useful to start antitubercular treatment.

  4. Biology of breast cancer during pregnancy using genomic profiling.

    Science.gov (United States)

    Azim, Hatem A; Brohée, Sylvain; Peccatori, Fedro A; Desmedt, Christine; Loi, Sherene; Lambrechts, Diether; Dell'Orto, Patrizia; Majjaj, Samira; Jose, Vinu; Rotmensz, Nicole; Ignatiadis, Michail; Pruneri, Giancarlo; Piccart, Martine; Viale, Giuseppe; Sotiriou, Christos

    2014-08-01

    Breast cancer during pregnancy is rare and is associated with relatively poor prognosis. No information is available on its biological features at the genomic level. Using a dataset of 54 pregnant and 113 non-pregnant breast cancer patients, we evaluated the pattern of hot spot somatic mutations and did transcriptomic profiling using Sequenom and Affymetrix respectively. We performed gene set enrichment analysis to evaluate the pathways associated with diagnosis during pregnancy. We also evaluated the expression of selected cancer-related genes in pregnant and non-pregnant patients and correlated the results with changes occurring in the normal breast using a pregnant murine model. We finally investigated aberrations associated with disease-free survival (DFS). No significant differences in mutations were observed. Of the total number of patients, 18.6% of pregnant and 23% of non-pregnant patients had a PIK3CA mutation. Around 30% of tumors were basal, with no differences in the distribution of breast cancer molecular subtypes between pregnant and non-pregnant patients. Two pathways were enriched in tumors diagnosed during pregnancy: the G protein-coupled receptor pathway and the serotonin receptor pathway (FDR pregnancy had higher expression of PD1 (PDCD1; P=0.015), PDL1 (CD274; P=0.014), and gene sets related to SRC (P=0.004), IGF1 (P=0.032), and β-catenin (P=0.019). Their expression increased almost linearly throughout gestation when evaluated on the normal breast using a pregnant mouse model underscoring the potential effect of the breast microenvironment on tumor phenotype. No genes were associated with DFS in a multivariate model, which could be due to low statistical power. Diagnosis during pregnancy impacts the breast cancer transcriptome including potential cancer targets.

  5. Induction of murine embryonic stem cell differentiation by medicinal plant extracts.

    Science.gov (United States)

    Reynertson, Kurt A; Charlson, Mary E; Gudas, Lorraine J

    2011-01-01

    Epidemiological evidence indicates that diets high in fruits and vegetables provide a measure of cancer chemoprevention due to phytochemical constituents. Natural products are a rich source of cancer chemotherapy drugs, and primarily target rapidly cycling tumor cells. Increasing evidence indicates that many cancers contain small populations of resistant, stem-like cells that have the capacity to regenerate tumors following chemotherapy and radiation, and have been linked to the initiation of metastases. Our goal is to discover natural product-based clinical or dietary interventions that selectively target cancer stem cells, inducing differentiation. We adapted an alkaline phosphatase (AP) stain to assay plant extracts for the capacity to induce differentiation in embryonic stem (ES) cells. AP is a characteristic marker of undifferentiated ES cells, and this represents a novel approach to screening medicinal plant extracts. Following a survey of approximately 100 fractions obtained from 12 species of ethnomedically utilized plants, we found fractions from 3 species that induced differentiation, decreasing AP and transcript levels of pluripotency markers (Nanog, Oct-4, Rex-1). These fractions affected proliferation of murine ES, and human embryonal, prostate, and breast carcinoma cells in a dose-dependent manner. Several phytochemical constituents were isolated; the antioxidant phytochemicals ellagic acid and gallic acid were shown to affect viability of cultured breast carcinoma cells. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Induction of murine embryonic stem cell differentiation by medicinal plant extracts

    Energy Technology Data Exchange (ETDEWEB)

    Reynertson, Kurt A. [Center for Complementary and Integrative Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States); Department of Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States); Charlson, Mary E. [Center for Complementary and Integrative Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States); Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States); Gudas, Lorraine J., E-mail: ljgudas@med.cornell.edu [Center for Complementary and Integrative Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States); Department of Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States); Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States)

    2011-01-01

    Epidemiological evidence indicates that diets high in fruits and vegetables provide a measure of cancer chemoprevention due to phytochemical constituents. Natural products are a rich source of cancer chemotherapy drugs, and primarily target rapidly cycling tumor cells. Increasing evidence indicates that many cancers contain small populations of resistant, stem-like cells that have the capacity to regenerate tumors following chemotherapy and radiation, and have been linked to the initiation of metastases. Our goal is to discover natural product-based clinical or dietary interventions that selectively target cancer stem cells, inducing differentiation. We adapted an alkaline phosphatase (AP) stain to assay plant extracts for the capacity to induce differentiation in embryonic stem (ES) cells. AP is a characteristic marker of undifferentiated ES cells, and this represents a novel approach to screening medicinal plant extracts. Following a survey of approximately 100 fractions obtained from 12 species of ethnomedically utilized plants, we found fractions from 3 species that induced differentiation, decreasing AP and transcript levels of pluripotency markers (Nanog, Oct-4, Rex-1). These fractions affected proliferation of murine ES, and human embryonal, prostate, and breast carcinoma cells in a dose-dependent manner. Several phytochemical constituents were isolated; the antioxidant phytochemicals ellagic acid and gallic acid were shown to affect viability of cultured breast carcinoma cells.

  7. Impact of tumour epithelial subtype on circulating microRNAs in breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Peadar S Waters

    Full Text Available While a range of miRNAs have been shown to be dysregulated in the circulation of patients with breast cancer, little is known about the relationship between circulating levels and tumour characteristics. The aim of this study was to analyse alterations in circulating miRNA expression during tumour progression in a murine model of breast cancer, and to detemine the clinical relevance of identified miRNAs at both tissue and circulating level in patient samples. Athymic nude mice received a subcutaneous or mammary fat pad injection of MDA-MB-231 cells. Blood sampling was performed at weeks 1, 3 and 6 following tumour induction, and microRNA extracted. MicroRNA microArray analysis was performed comparing samples harvested at week 1 to those collected at week 6 from the same animals. Significantly altered miRNAs were validated across all murine samples by RQ-PCR (n = 45. Three miRNAs of interest were then quantified in the circulation(n = 166 and tissue (n = 100 of breast cancer patients and healthy control individuals. MicroArray-based analysis of murine blood samples revealed levels of 77 circulating microRNAs to be changed during disease progression, with 44 demonstrating changes >2-fold. Validation across all samples revealed miR-138 to be significantly elevated in the circulation of animals during disease development, with miR-191 and miR-106a levels significantly decreased. Analysis of patient tissue and blood samples revealed miR-138 to be significantly up-regulated in the circulation of patients with breast cancer, with no change observed in the tissue setting. While not significantly changed overall in breast cancer patients compared to controls, circulating miR-106a and miR-191 were significantly decreased in patients with basal breast cancer. In tissue, both miRNAs were significantly elevated in breast cancer compared to normal breast tissue. The data demonstrates an impact of tumour epithelial subtype on circulating levels of

  8. Glucocorticoid receptors in murine erythroleukaemic cells

    Energy Technology Data Exchange (ETDEWEB)

    Hammond, K.D.; Torrance, J.M.; DiDomenico, M.

    1987-01-01

    Glucocorticoid receptors in murine erythroleukaemic cells were studied in relation to hexamethylene bisacetamide (HMBA) induced differentiation. Specific binding of dexamethasone was measured. A single class of saturable, high affinity binding sites was demonstrated in intact cells; with cell homogenates or fractions binding was low and could not be reliably quantified. Receptor binding in whole cell suspensions was lower in cells which had been treated with HMBA (36.5 +/- 8.2 pmol/g protein) than in untreated controls (87.9 +/- 23.6 pmol/g protein); dissociation constants were similar in treated (2.7 nM) and untreated cells (2.5 nM). Dexamethasone, hydrocortisone, corticosterone and progesterone competed with tritium-labelled dexamethasone for receptor binding sites; cortisone, deoxycorticosterone and oestradiol had little effect.

  9. Extracellular proteolysis in the adult murine brain.

    Science.gov (United States)

    Sappino, A P; Madani, R; Huarte, J; Belin, D; Kiss, J Z; Wohlwend, A; Vassalli, J D

    1993-08-01

    Plasminogen activators are important mediators of extracellular metabolism. In the nervous system, plasminogen activators are thought to be involved in the remodeling events required for cell migration during development and regeneration. We have now explored the expression of the plasminogen activator/plasmin system in the adult murine central nervous system. Tissue-type plasminogen activator is synthesized by neurons of most brain regions, while prominent tissue-type plasminogen activator-catalyzed proteolysis is restricted to discrete areas, in particular within the hippocampus and hypothalamus. Our observations indicate that tissue-type plasminogen activator-catalyzed proteolysis in neural tissues is not limited to ontogeny, but may also contribute to adult central nervous system physiology, for instance by influencing neuronal plasticity and synaptic reorganization. The identification of an extracellular proteolytic system active in the adult central nervous system may also help gain insights into the pathogeny of neurodegenerative disorders associated with extracellular protein deposition.

  10. Isolation and culture of murine macrophages.

    Science.gov (United States)

    Davies, John Q; Gordon, Siamon

    2005-01-01

    The two most convenient sources of primary murine macrophages are the bone marrow and the peritoneal cavity. Resident peritoneal macrophages can readily be harvested from mice and purified by adherence to tissue culture plastic. The injection of Bio-Gel polyacrylamide beads or thioglycollate broth into the peritoneal cavity produces an inflammatory response allowing the purification of large numbers of elicited macrophages. The production of an activated macrophage population can be achieved by using Bacillus-Calmette-Guerin as the inflammatory stimulus. Resident bone marrow macrophages can be isolated following enzymatic separation of cells from bone marrow plugs and enrichment on 30% fetal calf serum containing medium or Ficoll-Hypaque gradients. Bone marrow-derived macrophages can be produced by differentiating nonadherent macrophage precursors with medium containing macrophage colony-stimulating factor.

  11. Hypoxia increases the metastatic ability of breast cancer cells via upregulation of CXCR4

    LENUS (Irish Health Repository)

    Cronin, Patricia A

    2010-05-21

    Abstract Background Chemokine SDF1α and its unique receptor CXCR4 have been implicated in organ-specific metastases of many cancers including breast cancer. Hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. We hypothesized that hypoxia would upregulate CXCR4 expression and lead to increased chemotactic responsiveness to its specific ligand SDF1α. Methods Three breast cancer cell lines MDA-MB-231, MCF7 and 4T1 were subjected to 48 hrs of hypoxia or normoxia. Cell surface receptor expression was evaluated using flow cytometry. An extracellular matrix invasion assay and microporous migration assay was used to assess chemotactic response and metastatic ability. Results CXCR4 surface expression was significantly increased in the two human breast cancer cell lines, MDA-MB-231 and MCF7, following exposure to hypoxia. This upregulation of CXCR4 cell surface expression corresponded to a significant increase in migration and invasion in response to SDF1-α in vitro. The increase in metastatic potential of both the normoxic and the hypoxic treated breast cancer cell lines was attenuated by neutralization of CXCR4 with a CXCR4 neutralizing mAb, MAB172 or a CXCR4 antagonist, AMD3100, showing the relationship between CXCR4 overexpression and increased chemotactic responsiveness. Conclusions CXCR4 expression can be modulated by the tissue microenvironment such as hypoxia. Upregulation of CXCR4 is associated with increased migratory and invasive potential and this effect can be abrogated by CXCR4 inhibition. Chemokine receptor CXCR4 is a potential therapeutic target in the adjuvant treatment of breast cancer.

  12. Deptor enhances triple-negative breast cancer metastasis and chemoresistance through coupling to survivin expression.

    Science.gov (United States)

    Parvani, Jenny G; Davuluri, Gangarao; Wendt, Michael K; Espinosa, Christine; Tian, Maozhen; Danielpour, David; Sossey-Alaoui, Khalid; Schiemann, William P

    2015-03-01

    Transforming growth factor-β (TGF-β) functions to suppress tumorigenesis in normal mammary tissues and early-stage breast cancers and, paradoxically, acts to promote the metastasis and chemoresistance in late-stage breast cancers, particularly triple-negative breast cancers (TNBCs). Precisely how TGF-β acquires oncogenic characteristics in late-stage breast cancers remains unknown, as does the role of the endogenous mammalian target of rapamycin (mTOR) inhibitor, Dep domain-containing mTOR-interacting protein (Deptor), in coupling TGF-β to TNBC development and metastatic progression. Here we demonstrate that Deptor expression was downregulated in basal-like/TNBCs relative to their luminal counterparts. Additionally, Deptor expression was 1) inversely correlated with the metastatic ability of human (MCF10A) and mouse (4T1) TNBC progression series and 2) robustly repressed by several inducers of epithelial-mesenchymal transition programs. Functional disruption of Deptor expression in 4T07 cells significantly inhibited their proliferation and organoid growth in vitro, as well as prevented their colonization and tumor formation in the lungs of mice. In stark contrast, elevated Deptor expression was significantly associated with poorer overall survival of patients harboring estrogen receptor α-negative breast cancers. Accordingly, enforced Deptor expression in MDA-MB-231 cells dramatically enhanced their 1) organoid growth in vitro, 2) pulmonary outgrowth in mice, and 3) resistance to chemotherapies, an event dependent on the coupling of Deptor to survivin expression. Collectively, our findings highlight the dichotomous functions of Deptor in modulating the proliferation and survival of TNBCs during metastasis; they also implicate Deptor and its stimulation of survivin as essential components of TNBC resistance to chemotherapies and apoptotic stimuli.

  13. Deptor Enhances Triple-Negative Breast Cancer Metastasis and Chemoresistance through Coupling to Survivin Expression

    Directory of Open Access Journals (Sweden)

    Jenny G. Parvani

    2015-03-01

    Full Text Available Transforming growth factor–β (TGF-β functions to suppress tumorigenesis in normal mammary tissues and early-stage breast cancers and, paradoxically, acts to promote the metastasis and chemoresistance in late-stage breast cancers, particularly triple-negative breast cancers (TNBCs. Precisely how TGF-β acquires oncogenic characteristics in late-stage breast cancers remains unknown, as does the role of the endogenous mammalian target of rapamycin (mTOR inhibitor, Dep domain–containing mTOR-interacting protein (Deptor, in coupling TGF-β to TNBC development and metastatic progression. Here we demonstrate that Deptor expression was downregulated in basal-like/TNBCs relative to their luminal counterparts. Additionally, Deptor expression was 1 inversely correlated with the metastatic ability of human (MCF10A and mouse (4T1 TNBC progression series and 2 robustly repressed by several inducers of epithelial-mesenchymal transition programs. Functional disruption of Deptor expression in 4T07 cells significantly inhibited their proliferation and organoid growth in vitro, as well as prevented their colonization and tumor formation in the lungs of mice. In stark contrast, elevated Deptor expression was significantly associated with poorer overall survival of patients harboring estrogen receptor α–negative breast cancers. Accordingly, enforced Deptor expression in MDA-MB-231 cells dramatically enhanced their 1 organoid growth in vitro, 2 pulmonary outgrowth in mice, and 3 resistance to chemotherapies, an event dependent on the coupling of Deptor to survivin expression. Collectively, our findings highlight the dichotomous functions of Deptor in modulating the proliferation and survival of TNBCs during metastasis; they also implicate Deptor and its stimulation of survivin as essential components of TNBC resistance to chemotherapies and apoptotic stimuli.

  14. Breast Cancer Basics and You

    Science.gov (United States)

    ... in both men and women, although male breast cancer is rare. The Breasts Inside a woman's breast are 15 to 20 sections called lobes. Each lobe contains many smaller sections called lobules. These are groups of tiny glands that make breast milk. Breast milk flows through thin tubes called ducts ...

  15. Breast Tissue Composition and Susceptibility to Breast Cancer

    Science.gov (United States)

    Martin, Lisa J.; Bronskill, Michael; Yaffe, Martin J.; Duric, Neb; Minkin, Salomon

    2010-01-01

    Breast density, as assessed by mammography, reflects breast tissue composition. Breast epithelium and stroma attenuate x-rays more than fat and thus appear light on mammograms while fat appears dark. In this review, we provide an overview of selected areas of current knowledge about the relationship between breast density and susceptibility to breast cancer. We review the evidence that breast density is a risk factor for breast cancer, the histological and other risk factors that are associated with variations in breast density, and the biological plausibility of the associations with risk of breast cancer. We also discuss the potential for improved risk prediction that might be achieved by using alternative breast imaging methods, such as magnetic resonance or ultrasound. After adjustment for other risk factors, breast density is consistently associated with breast cancer risk, more strongly than most other risk factors for this disease, and extensive breast density may account for a substantial fraction of breast cancer. Breast density is associated with risk of all of the proliferative lesions that are thought to be precursors of breast cancer. Studies of twins have shown that breast density is a highly heritable quantitative trait. Associations between breast density and variations in breast histology, risk of proliferative breast lesions, and risk of breast cancer may be the result of exposures of breast tissue to both mitogens and mutagens. Characterization of breast density by mammography has several limitations, and the uses of breast density in risk prediction and breast cancer prevention may be improved by other methods of imaging, such as magnetic resonance or ultrasound tomography. PMID:20616353

  16. Breast abscesses after breast conserving therapy for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, Kazuhisa [National Kyoto Hospital (Japan)

    2001-09-01

    Breast abscess after breast conserving therapy is a rare complication and the study of this cause has not been reported. A retrospective review of 190 patients undergoing breast conserving therapy in our institution revealed 4 patients with breast abscess (mean age, 50.6 years; range, 47-57 years and median follow up 4 months; 1-11 months). Risk factors which were common to all patients were: fine needle aspiration (FNA), surgical treatment; wide excision, adjuvant therapy; oral administration of tamoxifen (TAM), radiation therapy (RT) to ipsilateral whole breast; total dose of 50 Gy and skin desquamation by RT; level I or II. Other important risk factors in 3 patients were repeated aspirations of seroma post operatively and 2 patients received chemotherapy; CAF. Cultures from one abscess grew staphylococcus aureus, one grew staphylococcus epidermidis, and two were sterile. Breast abscess may be caused by a variety of factors and it is often difficult to specify the cause. This suggests that careful observation will be necessary to determine the cause. (author)

  17. Breast cancer screening with digital breast tomosynthesis.

    Science.gov (United States)

    Skaane, Per

    2017-01-01

    To give an overview of studies comparing full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) in breast cancer screening. The implementation of tomosynthesis in breast imaging is rapidly increasing world-wide. Experimental clinical studies of relevance for DBT screening have shown that tomosynthesis might have a great potential in breast cancer screening, although most of these retrospective reading studies are based on small populations, so that final conclusions are difficult to draw from individual reports. Several retrospective studies and three prospective trials on tomosynthesis in breast cancer screening have been published so far, confirming the great potential of DBT in mammography screening. The main results of these screening studies are presented. The retrospective screening studies from USA have all shown a significant decrease in the recall rate using DBT as adjunct to mammography. Most of these studies have also shown an increase in the cancer detection rate, and the non-significant results in some studies might be explained by a lack of statistical power. All the three prospective European trials have shown a significant increase in the cancer detection rate. The retrospective and the prospective screening studies comparing FFDM and DBT have all demonstrated that tomosynthesis has a great potential for improving breast cancer screening. DBT should be regarded as a better mammogram that could improve or overcome limitations of the conventional mammography, and tomosynthesis might be considered as the new technique in the next future of breast cancer screening.

  18. Do We Know What Causes Breast Cancer?

    Science.gov (United States)

    ... Research? Breast Cancer About Breast Cancer How Does Breast Cancer Form? Changes or mutations in DNA can cause ... requests, please contact permissionrequest@cancer.org . More In Breast Cancer About Breast Cancer Risk and Prevention Early Detection ...

  19. Breast Cancer Early Detection and Diagnosis

    Science.gov (United States)

    ... En Español Category Cancer A-Z Breast Cancer Breast Cancer Early Detection and Diagnosis Breast cancer is sometimes ... cancer screening is so important. Learn more. Can Breast Cancer Be Found Early? Breast cancer is sometimes found ...

  20. Women with Saethre-Chotzen syndrome are at increased risk of breast cancer.

    Science.gov (United States)

    Sahlin, Pelle; Windh, Per; Lauritzen, Claes; Emanuelsson, Monica; Grönberg, Henrik; Stenman, Göran

    2007-07-01

    The Saethre-Chotzen syndrome is an autosomal, dominantly inherited craniosynostosis caused by mutations in the basic helix-loop-helix transcription factor gene TWIST1. This syndrome has hitherto not been associated with an increased risk of cancer. However, recent studies, using a murine breast tumor model, have shown that Twist may act as a key regulator of metastasis and that the gene is overexpressed in subsets of sporadic human breast cancers. Here, we report a novel association between the Saethre-Chotzen syndrome and breast cancer. In 15 Swedish Saethre-Chotzen families, 15 of 29 (52%) women carriers over the age of 25 had developed breast cancer. At least four patients developed breast cancer before 40 years of age, and five between 40 and 50 years of age. The observed cases with breast cancer (n = 15) are significantly higher than expected (n = 0.89), which gives a standardized incidence ratio (SIR) of 16.80 (95% CI 1.54-32.06). Our finding of a high frequency of breast cancer in women with the Saethre-Chotzen syndrome identifies breast cancer as an important and previously unrecognized symptom characteristic of this syndrome. The results strongly suggest that women carriers of this syndrome would benefit from genetic counseling and enrolment in surveillance programs including yearly mammography. Our results also indicate that the TWIST1 gene may be a novel breast cancer susceptibility gene. Additional studies are, however, necessary to reveal the mechanism by which TWIST1 may predispose to early onset breast cancer in Saethre-Chotzen patients.

  1. Breast Implants: Saline vs. Silicone

    Science.gov (United States)

    ... differ in material and consistency, however. Saline breast implants Saline implants are filled with sterile salt water. ... of any age for breast reconstruction. Silicone breast implants Silicone implants are pre-filled with silicone gel — ...

  2. General Information about Breast Cancer

    Science.gov (United States)

    ... Screening Research Breast Cancer Treatment (PDQ®)–Patient Version General Information About Breast Cancer Go to Health Professional ... are linked by thin tubes called ducts. Enlarge Anatomy of the female breast. The nipple and areola ...

  3. Breast Cancer and Bone Loss

    Science.gov (United States)

    ... Menopause Map Featured Resource Find an Endocrinologist Search Breast Cancer and Bone Loss July 2010 Download PDFs English ... G. Komen Foundation What is the link between breast cancer and bone loss? Certain treatments for breast cancer ...

  4. Breast lump removal - series (image)

    Science.gov (United States)

    ... a breast lump is very important to a patient's prognosis (probable outcome). Most breast lumps are not diagnosed at the ... is required. If the lump is malignant, the outcome depends on the ... lumpectomy does not require a breast replacement (prosthesis).

  5. CDC Vital Signs: Breast Cancer

    Science.gov (United States)

    ... 2.65 MB] Read the MMWR Science Clips Breast Cancer Black Women Have Higher Death Rates from Breast ... of Page U.S. State Info Number of Additional Breast Cancer Deaths Among Black Women, By State SOURCE: National ...

  6. Breast Cancer Rates by State

    Science.gov (United States)

    ... Associated Lung Ovarian Prostate Skin Uterine Cancer Home Breast Cancer Rates by State Language: English Español (Spanish) Recommend ... from breast cancer each year. Rates of Getting Breast Cancer by State The number of people who get ...

  7. Molecular cloning and chromosome assignment of murine N-ras.

    OpenAIRE

    Ryan, J.; Hart, C P; Ruddle, F H

    1984-01-01

    The murine N-ras gene was cloned by screening an EMBL-3 recombinant phage library with a human N-ras specific probe. Hybridization of two separate unique sequence N-ras probes, isolated from the 5' and 3' flanking sequences of the murine gene, to a mouse-Chinese hamster hybrid mapping panel assigns the N-ras locus to mouse chromosome three.

  8. Mimickers of breast malignancy on breast sonography.

    Science.gov (United States)

    Cho, So Hyun; Park, Sung Hee

    2013-11-01

    The aim of this article is to review benign breast lesions that can mimic carcinoma on sonography. Cases of benign lesions mimicking carcinoma on sonography were collected among lesions that were initially assessed as suspicious on sonography according to the American College of Radiology Breast Imaging Reporting and Data System category. Sonographically guided core needle biopsy was performed, and the pathologic types were confirmed to be benign. Cases of benign lesions mimicking carcinoma on sonography were shown to include fat necrosis, diabetic mastopathy, fibrocystic changes, sclerosing adenosis, ruptured inflammatory cysts, inflammatory abscesses, granulomatous mastitis, fibroadenomas, fibroadenomatous mastopathy, and apocrine metaplasia. Benign breast lesions may present with malignant features on imaging. A clear understanding of the range of appearances of benign breast lesions that mimic malignancy is important in radiologic-pathologic correlation to ensure that benign results are accepted when concordant with imaging and clinical features but, when discordant, there is no delay in further evaluation up to and including excisional biopsy.

  9. Anti-breast cancer properties and toxicity of Dillenia suffruticosa root aqueous extract in BALB/c mice

    Institute of Scientific and Technical Information of China (English)

    Latifah; Saiful; Yazan; Yong; Sze; Ong; Nur; Elena; Zaaba; Razana; Mohd; Ali; Jhi; Biau; Foo; Yin; Sim; Tor

    2015-01-01

    Objective:To determine the anti-breast cancer activities and the safety oral consumption of Dillenia suffruticosa root aqueous extract(DRAE)in BALB/c mice.Methods:In the anti-breast cancer study,female BALB/c mice were divided into five groups(n=12),which were(1)positive control(with breast cancer,untreated),(2)negative control(without breast cancer,untreated)and other three groups of mice with breast cancer treated with 1 000,500 and 250 mg/kg of DRAE,respectively,by oral gavage for 28 days.All mice except from the negative control group were injected into the mammary fat pad with 4T1 cells(1×1054T1 cells/0.1 m L of phosphate buffer solution).DRAE was administered orally on Day 11 after the tumor has developed.Results:The tumor volume of the 1 000 mg/kg of DRAE group reduced significantly compared to the positive control while treatment with 500 mg/kg of DRAE had significantly inhibited metastasis to the heart.In the acute toxicity study,treatment with up to5 000 mg/kg of DRAE was not toxic to the animals,indicating its safety when a large amount of this plant extract was ingested.Based on the sub-acute toxicity study,treatment of the highest dose of DRAE(1 000 mg/kg)had mild liver toxicity indicated by mild focal hemorrhage.Conclusions:DRAE possesses anti-breast cancer properties but at the same time it shows mild toxicity to the liver.The non observable adverse effect dose for DRAE is500 mg/kg.

  10. Breast reconstruction after mastectomy

    Directory of Open Access Journals (Sweden)

    Daniel eSchmauss

    2016-01-01

    Full Text Available Breast cancer is the leading cause of cancer death in women worldwide. Its surgical approach has become less and less mutilating in the last decades. However, the overall number of breast reconstructions has significantly increased lately. Nowadays breast reconstruction should be individualized at its best, first of all taking into consideration oncological aspects of the tumor, neo-/adjuvant treatment and genetic predisposition, but also its timing (immediate versus delayed breast reconstruction, as well as the patient’s condition and wish. This article gives an overview over the various possibilities of breast reconstruction, including implant- and expander-based reconstruction, flap-based reconstruction (vascularized autologous tissue, the combination of implant and flap, reconstruction using non-vascularized autologous fat, as well as refinement surgery after breast reconstruction.

  11. Bilateral primary breast lymphoma

    Institute of Scientific and Technical Information of China (English)

    Jung Im Yi; Byung Joo Chae; Ja Seong Bae; Bong Joo Kang; Ahwon Lee; Byung Joo Song; Sang Seol Jung

    2010-01-01

    @@ Primary breast lymphoma (PBL) is rare, accounting for 0.04%-0.50% of breast malignancies and 1.7% of extranodal lymphoma.1,2 The originally described diagnostic criteria for PBL2 remains the standard definition for this disease. These criteria are breast location as the clinical site of presentation, absence of history of previous lymphoma or evidence of widespread disease at diagnosis, close association of lymphoma with breast tissue in pathologic specimens, and involvement of ipsilateral lymph nodes if they develop simultaneously with PBL.

  12. [Breast reconstruction after mastectomy].

    Science.gov (United States)

    Ho Quoc, C; Delay, E

    2013-02-01

    The mutilating surgery for breast cancer causes deep somatic and psychological sequelae. Breast reconstruction can mitigate these effects and permit the patient to help rebuild their lives. The purpose of this paper is to focus on breast reconstruction techniques and on factors involved in breast reconstruction. The methods of breast reconstruction are presented: objectives, indications, different techniques, operative risks, and long-term monitoring. Many different techniques can now allow breast reconstruction in most patients. Clinical cases are also presented in order to understand the results we expect from a breast reconstruction. Breast reconstruction provides many benefits for patients in terms of rehabilitation, wellness, and quality of life. In our mind, breast reconstruction should be considered more as an opportunity and a positive choice (the patient can decide to do it), than as an obligation (that the patient would suffer). The consultation with the surgeon who will perform the reconstruction is an important step to give all necessary informations. It is really important that the patient could speak again with him before undergoing reconstruction, if she has any doubt. The quality of information given by medical doctors is essential to the success of psychological intervention. This article was written in a simple, and understandable way to help gynecologists giving the best information to their patients. It is maybe also possible to let them a copy of this article, which would enable them to have a written support and would facilitate future consultation with the surgeon who will perform the reconstruction.

  13. Overview of Genetically Engineered Mouse Models of Breast Cancer Used in Translational Biology and Drug Development.

    Science.gov (United States)

    Greenow, Kirsty R; Smalley, Matthew J

    2015-01-01

    Breast cancer is a heterogeneous condition with no single standard of treatment and no definitive method for determining whether a tumor will respond to therapy. The development of murine models that faithfully mimic specific human breast cancer subtypes is critical for the development of patient-specific treatments. While the artificial nature of traditional in vivo xenograft models used to characterize novel anticancer treatments has limited clinical predictive value, the development of genetically engineered mouse models (GEMMs) makes it possible to study the therapeutic responses in an intact microenvironment. GEMMs have proven to be an experimentally tractable platform for evaluating the efficacy of novel therapeutic combinations and for defining the mechanisms of acquired resistance. Described in this overview are several of the more popular breast cancer GEMMs, including details on their value in elucidating the molecular mechanisms of this disorder.

  14. Expression and function of the protein tyrosine phosphatase receptor J (PTPRJ) in normal mammary epithelial cells and breast tumors.

    Science.gov (United States)

    Smart, Chanel E; Askarian Amiri, Marjan E; Wronski, Ania; Dinger, Marcel E; Crawford, Joanna; Ovchinnikov, Dmitry A; Vargas, Ana Cristina; Reid, Lynne; Simpson, Peter T; Song, Sarah; Wiesner, Christiane; French, Juliet D; Dave, Richa K; da Silva, Leonard; Purdon, Amy; Andrew, Megan; Mattick, John S; Lakhani, Sunil R; Brown, Melissa A; Kellie, Stuart

    2012-01-01

    The protein tyrosine phosphatase receptor J, PTPRJ, is a tumor suppressor gene that has been implicated in a range of cancers, including breast cancer, yet little is known about its role in normal breast physiology or in mammary gland tumorigenesis. In this paper we show that PTPRJ mRNA is expressed in normal breast tissue and reduced in corresponding tumors. Meta-analysis revealed that the gene encoding PTPRJ is frequently lost in breast tumors and that low expression of the transcript associated with poorer overall survival at 20 years. Immunohistochemistry of PTPRJ protein in normal human breast tissue revealed a distinctive apical localisation in the luminal cells of alveoli and ducts. Qualitative analysis of a cohort of invasive ductal carcinomas revealed retention of normal apical PTPRJ localization where tubule formation was maintained but that tumors mostly exhibited diffuse cytoplasmic staining, indicating that dysregulation of localisation associated with loss of tissue architecture in tumorigenesis. The murine ortholog, Ptprj, exhibited a similar localisation in normal mammary gland, and was differentially regulated throughout lactational development, and in an in vitro model of mammary epithelial differentiation. Furthermore, ectopic expression of human PTPRJ in HC11 murine mammary epithelial cells inhibited dome formation. These data indicate that PTPRJ may regulate differentiation of normal mammary epithelia and that dysregulation of protein localisation may be associated with tumorigenesis.

  15. Research on Growth Behavior of Embryos for Bovine and Murine on Primary Murine Embryos Fibroblast Cell Feeder Layer

    Institute of Scientific and Technical Information of China (English)

    AN Li-long; XIAO Mei; FENG Xiu-Liang; DOU Zhong-ying; QIU Huai; YANG Qi; LEI An-min; YANG Chun-rong; GAO Zhi-min

    2002-01-01

    The difference in growth behavior between bovine embryos and murine embryos was studied on PMEF(primary murine embryos fibroblast)feeder layer. The results showed as follows: With embryos having attached, bovine embryonic trophoblast formed a transparent membranous structure covering on inner cell mass (ICM), however, murine embryonic trophoblast formed disc structure. Bovine embryos formed four kinds of ICM colonies with different morphology including the mass-like, the net-like, the stream-like and the mixture-like colonies. Compared with Murine ICM, the bovine ICM grew more fast. So, the bovine ICM was passaged at first after a culture of approximately 5 - 6 days in vitro, but murine ICM was passaged at first after an attachment of 3 - 4 days on PMEF feeder layer. The mixture colonies of bovine ICM differentiated very early, while the others differentiated very late. Most ICM-like mass of Bovine grew in a defined spot, but bovine ICMs like stream and ICMs like net proliferated fast and dispersed quickly. We found that the single blastomeres derived from late bovine morula and late murine morula formed sub-blastophere; moreover, the bovine ICM cell would differentiate rapidly if the trophoblast was removed.

  16. Dual-wavelength imaging of tumor progression by activatable and targeting near-infrared fluorescent probes in a bioluminescent breast cancer model.

    Directory of Open Access Journals (Sweden)

    Bang-Wen Xie

    Full Text Available Bioluminescence imaging (BLI has shown its appeal as a sensitive technique for in vivo whole body optical imaging. However, the development of injectable tumor-specific near-infrared fluorescent (NIRF probes makes fluorescence imaging (FLI a promising alternative to BLI in situations where BLI cannot be used or is unwanted (e.g., spontaneous transgenic tumor models, or syngeneic mice to study immune effects.In this study, we addressed the questions whether it is possible to detect tumor progression using FLI with appropriate sensitivity and how FLI correlates with BLI measurements. In addition, we explored the possibility to simultaneously detect multiple tumor characteristics by dual-wavelength FLI (~700 and ~800 nm in combination with spectral unmixing. Using a luciferase-expressing 4T1-luc2 mouse breast cancer model and combinations of activatable and targeting NIRF probes, we showed that the activatable NIRF probes (ProSense680 and MMPSense680 and the targeting NIRF probes (IRDye 800CW 2-DG and IRDye 800CW EGF were either activated by or bound to 4T1-luc2 cells. In vivo, we implanted 4T1-luc2 cells orthotopically in nude mice and were able to follow tumor progression longitudinally both by BLI and dual-wavelength FLI. We were able to reveal different probe signals within the tumor, which co-localized with immuno-staining. Moreover, we observed a linear correlation between the internal BLI signals and the FLI signals obtained from the NIRF probes. Finally, we could detect pulmonary metastases both by BLI and FLI and confirmed their presence histologically.Taken together, these data suggest that dual-wavelength FLI is a feasible approach to simultaneously detect different features of one tumor and to follow tumor progression with appropriate specificity and sensitivity. This study may open up new perspectives for the detection of tumors and metastases in various experimental models and could also have clinical applications, such as image

  17. Metabolic syndrome components in murine models.

    Science.gov (United States)

    Lawson, Heather A; Cheverud, James M

    2010-03-01

    Animal models have enriched understanding of the physiological basis of metabolic disorders and advanced identification of genetic risk factors underlying the metabolic syndrome (MetS). Murine models are especially appropriate for this type of research, and are an excellent resource not only for identifying candidate genomic regions, but also for illuminating the possible molecular mechanisms or pathways affected in individual components of MetS. In this review, we briefly discuss findings from mouse models of metabolic disorders, particularly in light of issues raised by the recent flood of human genome-wide association studies (GWAS) results. We describe how mouse models are revealing that genotype interacts with environment in important ways, indicating that the underlying genetics of MetS is highly context dependant. Further we show that epistasis, imprinting and maternal effects each contribute to the genetic architecture underlying variation in metabolic traits, and mouse models provide an opportunity to dissect these aspects of the genetic architecture that are difficult if not impossible to ascertain in humans. Finally we discuss how knowledge gained from mouse models can be used in conjunction with comparative genomic methods and bioinformatic resources to inform human MetS research.

  18. Proteomic analysis of normal murine brain parts.

    Science.gov (United States)

    Taraslia, Vasiliki K; Kouskoukis, Alexandros; Anagnostopoulos, Athanasios K; Stravopodis, Dimitrios J; Margaritis, Lukas H; Tsangaris, George Th

    2013-01-01

    Murine brain is an excellent tool for studying protein expression and brain function in mammals. Although mice are an extensively used model to recapitulate various pathological conditions, the proteome of the normal mouse brain has not been yet reported. In the present study, we identified the total proteins of different parts of the brain of CB7BL/6 mice, a widely used strain, by applying proteomic methodologies. The adult mouse brain was dissected anatomically into the following regions: frontal cortex, olfactory bulb, hippocampus, midbrain, cerebellum, hypothalamus and medulla. Total protein extracts of these regions were separated by two-dimensional gel electrophoresis and analyzed by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry, following in-gel digestion with trypsin. Protein identification was carried out by peptide mass fingerprint. Thus, 515 different single-gene products were identified in total, 54 expressed specifically in the olfactory bulb, 62 in the hippocampus, 36 in the frontal cortex, five in the cerebellum, nine in the midbrain, eight in the hypothamamus and 10 in the medulla. The majority of the proteins were enzymes, structural proteins and transporters. Moreover, the distribution of these molecules appears to exhibit direct correlation with the function of the brain regions where they were expressed. This study leads to the complete characterization of the normal mouse brain proteome as well as the protein expression profile of the different brain regions. These results will aid in addressing unmet scientific needs regarding physiological and pathological brain functions.

  19. Amphotropic murine leukemia viruses induce spongiform encephalomyelopathy.

    Science.gov (United States)

    Münk, C; Löhler, J; Prassolov, V; Just, U; Stockschläder, M; Stocking, C

    1997-05-27

    Recombinants of amphotropic murine leukemia virus (A-MuLV) have found widespread use in retroviral vector systems due to their ability to efficiently and stably infect cells of several different species, including human. Previous work has shown that replication-competent recombinants containing the amphotropic env gene, encoding the major SU envelope glycoprotein that determines host tropism, induce lymphomas in vivo. We show here that these viruses also induce a spongiform encephalomyelopathy in mice inoculated perinatally. This fatal central nervous system disease is characterized by noninflammatory spongiform lesions of nerve and glial cells and their processes, and is associated with moderate astro- and microgliosis. The first clinical symptoms are ataxia, tremor, and spasticity, progressing to complete tetraparesis and incontinence, and finally death of the animal. Sequences within the amphotropic env gene are necessary for disease induction. Coinfection of A-MuLV recombinants with nonneuropathogenic ecotropic or polytropic MuLV drastically increases the incidence, degree, and distribution of the neurodegenerative disorder. The consequence of these results in view of the use of A-MuLV recombinants in the clinic is discussed.

  20. Glycosaminoglycan interactions in murine gammaherpesvirus-68 infection.

    Directory of Open Access Journals (Sweden)

    Laurent Gillet

    Full Text Available Glycosaminoglycans (GAGs commonly participate in herpesvirus entry. They are thought to provide a reversible attachment to cells that promotes subsequent receptor binding. Murine gamma-herpesvirus-68 (MHV-68 infection of fibroblasts and epithelial cells is highly GAG-dependent. This is a function of the viral gp150, in that gp150-deficient mutants are much less GAG-dependent than wild-type. Here we show that the major MHV-68 GAG-binding protein is not gp150 but gp70, a product of ORF4. Surprisingly, ORF4-deficient MHV-68 showed normal cell binding and was more sensitive than wild-type to inhibition by soluble heparin rather than less. Thus, the most obvious viral GAG interaction made little direct contribution to infection. Indeed, a large fraction of the virion gp70 had its GAG-binding domain removed by post-translational cleavage. ORF4 may therefore act mainly to absorb soluble GAGs and prevent them from engaging gp150 prematurely. In contrast to gp70, gp150 bound poorly to GAGs, implying that it provides little in the way of adhesion. We hypothesize that it acts instead as a GAG-sensitive switch that selectively activates MHV-68 entry at cell surfaces.

  1. Sinomenine inhibits breast cancer cell invasion and migration by suppressing NF-κB activation mediated by IL-4/miR-324-5p/CUEDC2 axis

    Energy Technology Data Exchange (ETDEWEB)

    Song, Lingqin, E-mail: qinlingsongxa@163.com [Department of Oncology, The Second Affiliated Hospital, Medical School of Xi' an Jiaotong University, Xi' an 710004 (China); Liu, Di; Zhao, Yang [Department of Oncology, The Second Affiliated Hospital, Medical School of Xi' an Jiaotong University, Xi' an 710004 (China); He, Jianjun [Department of Surgical Oncology, The First Affiliated Hospital, Medical School of Xi' an Jiaotong University, Xi' an 710061 (China); Kang, Huafeng; Dai, Zhijun; Wang, Xijing; Zhang, Shuqun; Zan, Ying [Department of Oncology, The Second Affiliated Hospital, Medical School of Xi' an Jiaotong University, Xi' an 710004 (China)

    2015-08-28

    Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a vital transcription factor that regulates multiple important biological processes, including the epithelial–mesenchymal transition (EMT) and metastasis of breast cancer. Sinomenine is an isoquinoline well known for its remarkable curative effect on rheumatic and arthritic diseases and can induce apoptosis of several cancer cell types. Recently, sinomenine was reported as a tumor suppressor via inhibiting cell proliferation and inducing apoptosis. However, the role and mechanism of sinomenine in invasion and metastasis of breast cancer are largely unknown. Here, we report that sinomenine suppressed the invasion and migration of MDA-MB-231 and 4T1 breast cancer cells in a dose-dependent manner. We detected binding of NF-κB to the inhibitor of NF-κB (IκB) after the MDA-MB-231 cells were treated with 0.25, 0.5, and 1 mM sinomenine. Co-IP analysis revealed that sinomenine enhanced the binding of NF-κB and IκB in a dose-dependent manner, suggesting that sinomenine had an effect on inactivation of NF-κB. Western blotting and ELISA approaches indicated that the suppression effect was closely associated with the phosphorylation of IκB kinase (IKK) and its negative regulator CUEDC2. Sinomenine treatment decreased miR-324-5p expression, thus increased the level of its target gene CUEDC2, and then blocked the phosphorylation of IKK through altering the upstream axis. Finally, transfection of a miR-324-5p mimic inhibited the suppression of invasion and metastasis of MDA-MB-231 and 4T1 cell by sinomenine, providing evidence that sinomenine treatment suppressed breast cancer cell invasion and metastasis via regulation of the IL4/miR-324-5p/CUEDC2 axis. Our findings reveal a novel mechanism by which sinomenine suppresses cancer cell invasion and metastasis, i.e., blocking NF-κB activation. - Highlights: • Sinomenine reduced invasion and migration of MDA-MB-231 and 4T1 breast cancer cells.

  2. The DNA cytosine deaminase APOBEC3B promotes tamoxifen resistance in ER-positive breast cancer

    Science.gov (United States)

    Law, Emily K.; Sieuwerts, Anieta M.; LaPara, Kelly; Leonard, Brandon; Starrett, Gabriel J.; Molan, Amy M.; Temiz, Nuri A.; Vogel, Rachel Isaksson; Meijer-van Gelder, Marion E.; Sweep, Fred C. G. J.; Span, Paul N.; Foekens, John A.; Martens, John W. M.; Yee, Douglas; Harris, Reuben S.

    2016-01-01

    Breast tumors often display extreme genetic heterogeneity characterized by hundreds of gross chromosomal aberrations and tens of thousands of somatic mutations. Tumor evolution is thought to be ongoing and driven by multiple mutagenic processes. A major outstanding question is whether primary tumors have preexisting mutations for therapy resistance or whether additional DNA damage and mutagenesis are necessary. Drug resistance is a key measure of tumor evolvability. If a resistance mutation preexists at the time of primary tumor presentation, then the intended therapy is likely to fail. However, if resistance does not preexist, then ongoing mutational processes still have the potential to undermine therapeutic efficacy. The antiviral enzyme APOBEC3B (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3B) preferentially deaminates DNA C-to-U, which results in signature C-to-T and C-to-G mutations commonly observed in breast tumors. We use clinical data and xenograft experiments to ask whether APOBEC3B contributes to ongoing breast tumor evolution and resistance to the selective estrogen receptor modulator, tamoxifen. First, APOBEC3B levels in primary estrogen receptor–positive (ER+) breast tumors inversely correlate with the clinical benefit of tamoxifen in the treatment of metastatic ER+ disease. Second, APOBEC3B depletion in an ER+ breast cancer cell line results in prolonged tamoxifen responses in murine xenograft experiments. Third, APOBEC3B overexpression accelerates the development of tamoxifen resistance in murine xenograft experiments by a mechanism that requires the enzyme’s catalytic activity. These studies combine to indicate that APOBEC3B promotes drug resistance in breast cancer and that inhibiting APOBEC3B-dependent tumor evolvability may be an effective strategy to improve efficacies of targeted cancer therapies. PMID:27730215

  3. Synchronous bilateral breast cancer in a male

    Science.gov (United States)

    Rubio Hernández, María Caridad; Díaz Prado, Yenia Ivet; Pérez, Suanly Rodríguez; Díaz, Ronald Rodríguez; Aleaga, Zaili Gutiérrez

    2013-01-01

    Male breast cancer, which represents only 1% of all breast cancers, is occasionally associated with a family history of breast cancer. Sporadic male breast cancers presenting with another primary breast cancer are extremely rare. In this article, we report on a 70-year-old male patient with bilateral multifocal and synchronous breast cancer and without a family history of breast cancer. PMID:24319497

  4. Breast Cancer Immunotherapy

    Institute of Scientific and Technical Information of China (English)

    JuhuaZhou; YinZhong

    2004-01-01

    Breast cancer is a leading cause of cancer-related deaths in women worldwide. Although tumorectomy, radiotherapy, chemotherapy and hormone replacement therapy have been used for the treatment of breast cancer, there is no effective therapy for patients with invasive and metastatic breast cancer. Immunotherapy may be proved effective in treating patients with advanced breast cancer. Breast cancer immunotherapy includes antibody based immunotherapy, cancer vaccine immunotherapy, adoptive T cell transfer immunotherapy and T cell receptor gene transfer immunotherapy. Antibody based immunotherapy such as the monoclonal antibody against HER-2/neu (trastuzumab) is successfully used in the treatment of breast cancer patients with over-expressed HER-2/neu, however, HER-2/neu is over-expressed only in 25-30% of breast cancer patients. Cancer vaccine immunotherapy is a promising method to treat cancer patients. Cancer vaccines can be used to induce specific anti-tumor immunity in breast cancer patients, but cannot induce objective tumor regression. Adoptive T cell transfer immunotherapy is an effective method in the treatment of melanoma patients. Recent advances in anti-tumor T cell generation ex vivo and limited clinical trial data have made the feasibility of adoptive T cell transfer immunotherapy in the treatment of breast cancer patients. T cell receptor gene transfer can redirect the specificity of T cells. Chimeric receptor, scFv(anti-HER-2/neu)/zeta receptor, was successfully used to redirect cytotoxic T lymphocyte hybridoma cells to obtain anti-HER-2/neu positive tumor cells, suggesting the feasibility of treatment of breast cancer patients with T cell receptor gene transfer immunotherapy. Clinical trials will approve that immunotherapy is an effective method to cure breast cancer disease in the near future. Cellular & Molecular Immunology.

  5. Breast Cancer Immunotherapy

    Institute of Scientific and Technical Information of China (English)

    Juhua Zhou; Yin Zhong

    2004-01-01

    Breast cancer is a leading cause of cancer-related deaths in women worldwide. Although tumorectomy,radiotherapy, chemotherapy and hormone replacement therapy have been used for the treatment of breast cancer, there is no effective therapy for patients with invasive and metastatic breast cancer. Immunotherapy may be proved effective in treating patients with advanced breast cancer. Breast cancer immunotherapy includes antibody based immunotherapy, cancer vaccine immunotherapy, adoptive T cell transfer immunotherapy and T cell receptor gene transfer immunotherapy. Antibody based immunotherapy such as the monoclonal antibody against HER-2/neu (trastuzumab) is successfully used in the treatment of breast cancer patients with over-expressed HER-2/neu, however, HER-2/neu is over-expressed only in 25-30% of breast cancer patients. Cancer vaccine immunotherapy is a promising method to treat cancer patients. Cancer vaccines can be used to induce specific anti-tumor immunity in breast cancer patients, but cannot induce objective tumor regression. Adoptive T cell transfer immunotherapy is an effective method in the treatment of melanoma patients. Recent advances in anti-tumor T cell generation ex vivo and limited clinical trial data have made the feasibility of adoptive T cell transfer immunotherapy in the treatment of breast cancer patients. T cell receptor gene transfer can redirect the specificity of T cells. Chimeric receptor, scFv(anti-HER-2/neu)/zeta receptor, was successfully used to redirect cytotoxic T lymphocyte hybridoma cells to obtain anti-HER-2/neu positive tumor cells, suggesting the feasibility of treatment of breast cancer patients with T cell receptor gene transfer immunotherapy. Clinical trials will approve that immunotherapy is an effective method to cure breast cancer disease in the near future.

  6. Breast cancer statistics, 2011.

    Science.gov (United States)

    DeSantis, Carol; Siegel, Rebecca; Bandi, Priti; Jemal, Ahmedin

    2011-01-01

    In this article, the American Cancer Society provides an overview of female breast cancer statistics in the United States, including trends in incidence, mortality, survival, and screening. Approximately 230,480 new cases of invasive breast cancer and 39,520 breast cancer deaths are expected to occur among US women in 2011. Breast cancer incidence rates were stable among all racial/ethnic groups from 2004 to 2008. Breast cancer death rates have been declining since the early 1990s for all women except American Indians/Alaska Natives, among whom rates have remained stable. Disparities in breast cancer death rates are evident by state, socioeconomic status, and race/ethnicity. While significant declines in mortality rates were observed for 36 states and the District of Columbia over the past 10 years, rates for 14 states remained level. Analyses by county-level poverty rates showed that the decrease in mortality rates began later and was slower among women residing in poor areas. As a result, the highest breast cancer death rates shifted from the affluent areas to the poor areas in the early 1990s. Screening rates continue to be lower in poor women compared with non-poor women, despite much progress in increasing mammography utilization. In 2008, 51.4% of poor women had undergone a screening mammogram in the past 2 years compared with 72.8% of non-poor women. Encouraging patients aged 40 years and older to have annual mammography and a clinical breast examination is the single most important step that clinicians can take to reduce suffering and death from breast cancer. Clinicians should also ensure that patients at high risk of breast cancer are identified and offered appropriate screening and follow-up. Continued progress in the control of breast cancer will require sustained and increased efforts to provide high-quality screening, diagnosis, and treatment to all segments of the population.

  7. Endocrine determinants of breast density and breast cancer

    NARCIS (Netherlands)

    Verheus, M.

    2007-01-01

    Worldwide, breast cancer is the most common malignancy among females. The total breast area on a mammogram can be dived in a radiologicaly dense area (glandular and stromal tissue) and a non-dense area (mainly fat tissue). Women with a high proportion of dense breast tissue (percent breast density)

  8. Endocrine determinants of breast density and breast cancer

    NARCIS (Netherlands)

    Verheus, M.

    2007-01-01

    Worldwide, breast cancer is the most common malignancy among females. The total breast area on a mammogram can be dived in a radiologicaly dense area (glandular and stromal tissue) and a non-dense area (mainly fat tissue). Women with a high proportion of dense breast tissue (percent breast density)

  9. Girls' Attitudes toward Breast Care and Breast Self-Examination.

    Science.gov (United States)

    Hadranyi, B. T.

    A study explored girls' emerging attitudes toward breast care and breast self-exam (BSE) and the extent to which girls had given thought to these issues. Analyses focused specifically on individual differences related to age, stage of breast development, perceived normalcy of breast development, and body image. The sample consisted of 43 white,…

  10. EPCR promotes breast cancer progression by altering SPOCK1/testican 1-mediated 3D growth

    Directory of Open Access Journals (Sweden)

    Naiara Perurena

    2017-01-01

    Full Text Available Abstract Background Activated protein C/endothelial protein C receptor (APC/EPCR axis is physiologically involved in anticoagulant and cytoprotective activities in endothelial cells. Emerging evidence indicates that EPCR also plays a role in breast stemness and human tumorigenesis. Yet, its contribution to breast cancer progression and metastasis has not been elucidated. Methods Transcriptomic status of EPCR was examined in a cohort of 286 breast cancer patients. Cell growth kinetics was evaluated in control and EPCR and SPARC/osteonectin, Cwcv, and kazal-like domains proteoglycan (SPOCK1/testican 1 silenced breast cancer cells in 2D, 3D, and in co-culture conditions. Orthotopic tumor growth and lung and osseous metastases were evaluated in several human and murine xenograft breast cancer models. Tumor-stroma interactions were further studied in vivo by immunohistochemistry and flow cytometry. An EPCR-induced gene signature was identified by microarray analysis. Results Analysis of a cohort of breast cancer patients revealed an association of high EPCR levels with adverse clinical outcome. Interestingly, EPCR knockdown did not affect cell growth kinetics in 2D but significantly reduced cell growth in 3D cultures. Using several human and murine xenograft breast cancer models, we showed that EPCR silencing reduced primary tumor growth and secondary outgrowths at metastatic sites, including the skeleton and the lungs. Interestingly, these effects were independent of APC ligand stimulation in vitro and in vivo. Transcriptomic analysis of EPCR-silenced tumors unveiled an effect mediated by matricellular secreted proteoglycan SPOCK1/testican 1. Interestingly, SPOCK1 silencing suppressed in vitro 3D growth. Moreover, SPOCK1 ablation severely decreased orthotopic tumor growth and reduced bone metastatic osteolytic tumors. High SPOCK1 levels were also associated with poor clinical outcome in a subset breast cancer patients. Our results suggest that EPCR

  11. Contralateral breast dose from partial breast brachytherapy.

    Science.gov (United States)

    Robinson, R Cole; Nelson, Christopher L; Bloom, Elizabeth S; Kisling, Kelly D; Mason, Bryan E; Fisher, Gary D; Kirsner, Steven M

    2015-11-08

    The purpose of this study was to determine the dose to the contralateral breast during accelerated partial breast irradiation (APBI) and to compare it to external beam-published values. Thermoluminescent dosimeter (TLD) packets were used to measure the dose to the most medial aspect of the contralateral breast during APBI simulation, daily quality assurance (QA), and treatment. All patients in this study were treated with a single-entry, multicatheter device for 10 fractions to a total dose of 34 Gy. A mark was placed on the patient's skin on the medial aspect of the opposite breast. Three TLD packets were taped to this mark during the pretreatment simulation. Simulations consisted of an AP and Lateral scout and a limited axial scan encompassing the lumpectomy cavity (miniscan), if rotation was a concern. After the simulation the TLD packets were removed and the patients were moved to the high-dose-rate (HDR) vault where three new TLD packets were taped onto the patients at the skin mark. Treatment was administered with a Nucletron HDR afterloader using Iridium-192 as the treatment source. Post-treatment, TLDs were read (along with the simulation and QA TLD and a set of standards exposed to a known dose of 6 MV photons). Measurements indicate an average total dose to the contralateral breast of 70 cGy for outer quadrant implants and 181 cGy for inner quadrant implants. Compared to external beam breast tangents, these results point to less dose being delivered to the contralateral breast when using APBI.

  12. Antitumor Activity and Immune Enhancement of Murine Interleukin-23 Expressed in Murine Colon Carcinoma Cells

    Institute of Scientific and Technical Information of China (English)

    Baoen Shan; Jingsheng Hao; Qiaoxia Li; Masatoshi Tagawa

    2006-01-01

    Interleukin (IL)-23, a cytokine composed of p19 and the p40 subunit of IL-12, can enhance the proliferation of memory T cells and production of IFN-γ from activated T cells. It can also induce antitumor effects in murine model. To further evaluate the antitumor activity and immune enhancement of IL-23 in vivo, murine colon carcinoma cells retrovirally transduced with mIL-23 gene were injected subcutaneously (s.c.) into BALB/c mice.Survival time and tumor volume were observed. LDH release assay, [3H]-TdR incorporation assay and ELISA were used to determine CTL activity, proliferation of splenocytes and level of cytokines, respectively. Number of dendritic cells (DCs) was analyzed by flow cytometry (FCM). IL-23 secreted by Colon26/IL-23 cells suppressed the growth of tumor and prolonged the survival time of mice, enhanced proliferation of splenocytes, CTL activity, and number of DCs. IL-23 also promoted the production of Th1 cytokines such as IFN-γ, IL-12 and TNF-o. However,the level of IL-4 was not enhanced significantly. These data suggested that IL-23 secreted by tumor cells can induce antitumor activity by enhancing immune response.

  13. Tumor cell migration screen identifies SRPK1 as breast cancer metastasis determinant

    Science.gov (United States)

    van Roosmalen, Wies; Le Dévédec, Sylvia E.; Golani, Ofra; Smid, Marcel; Pulyakhina, Irina; Timmermans, Annemieke M.; Look, Maxime P.; Zi, Di; Pont, Chantal; de Graauw, Marjo; Naffar-Abu-Amara, Suha; Kirsanova, Catherine; Rustici, Gabriella; Hoen, Peter A.C. ‘t; Martens, John W.M.; Foekens, John A.; Geiger, Benjamin; van de Water, Bob

    2015-01-01

    Tumor cell migration is a key process for cancer cell dissemination and metastasis that is controlled by signal-mediated cytoskeletal and cell matrix adhesion remodeling. Using a phagokinetic track assay with migratory H1299 cells, we performed an siRNA screen of almost 1,500 genes encoding kinases/phosphatases and adhesome- and migration-related proteins to identify genes that affect tumor cell migration speed and persistence. Thirty candidate genes that altered cell migration were validated in live tumor cell migration assays. Eight were associated with metastasis-free survival in breast cancer patients, with integrin β3–binding protein (ITGB3BP), MAP3K8, NIMA-related kinase (NEK2), and SHC-transforming protein 1 (SHC1) being the most predictive. Examination of genes that modulate migration indicated that SRPK1, encoding the splicing factor kinase SRSF protein kinase 1, is relevant to breast cancer outcomes, as it was highly expressed in basal breast cancer. Furthermore, high SRPK1 expression correlated with poor breast cancer disease outcome and preferential metastasis to the lungs and brain. In 2 independent murine models of breast tumor metastasis, stable shRNA-based SRPK1 knockdown suppressed metastasis to distant organs, including lung, liver, and spleen, and inhibited focal adhesion reorganization. Our study provides comprehensive information on the molecular determinants of tumor cell migration and suggests that SRPK1 has potential as a drug target for limiting breast cancer metastasis. PMID:25774502

  14. Delayed breast implant reconstruction

    DEFF Research Database (Denmark)

    Hvilsom, Gitte B.; Hölmich, Lisbet R.; Steding-Jessen, Marianne;

    2012-01-01

    We evaluated the association between radiation therapy and severe capsular contracture or reoperation after 717 delayed breast implant reconstruction procedures (288 1- and 429 2-stage procedures) identified in the prospective database of the Danish Registry for Plastic Surgery of the Breast during...... reconstruction approaches other than implants should be seriously considered among women who have received radiation therapy....

  15. BREAST CANCER AND EXERCISE

    Science.gov (United States)

    2008-03-19

    Prevent Osteoporosis and Osteoporotic Fractures; Improve Quality of Life; Improve Weight Control, and Muscular and Cardiovascular Fitness; Help the Patients to Return to Working Life; Reduce the Risk of Breast Cancer Recurrence; Prevent Other Diseases and Reduce All-Cause Mortality in Patients With Primary Breast Cancer.

  16. Primary osteosarcoma of breast

    Science.gov (United States)

    Gull, Sadaf; Patil, Prashant; Spence, Roy AJ

    2011-01-01

    Primary osteosarcoma of breast is rare. The authors present a case of a 51-year-old female who was admitted with a large necrotising tumour involving the right breast. CT scan confirmed chest wall invasion along with a solitary lung metastasis. She underwent a primary mastectomy with chest wall reconstruction. Unfortunately 3 months later she developed local recurrence. PMID:22688473

  17. Androgens and the breast.

    Science.gov (United States)

    Dimitrakakis, Constantine; Bondy, Carolyn

    2009-01-01

    Androgens have important physiological effects in women while at the same time they may be implicated in breast cancer pathologies. However, data on the effects of androgens on mammary epithelial proliferation and/or breast cancer incidence are not in full agreement. We performed a literature review evaluating current clinical, genetic and epidemiological data regarding the role of androgens in mammary growth and neoplasia. Epidemiological studies appear to have significant methodological limitations and thus provide inconclusive results. The study of molecular defects involving androgenic pathways in breast cancer is still in its infancy. Clinical and nonhuman primate studies suggest that androgens inhibit mammary epithelial proliferation and breast growth while conventional estrogen treatment suppresses endogenous androgens. Abundant clinical evidence suggests that androgens normally inhibit mammary epithelial proliferation and breast growth. Suppression of androgens using conventional estrogen treatment may thus enhance estrogenic breast stimulation and possibly breast cancer risk. Addition of testosterone to the usual hormone therapy regimen may diminish the estrogen/progestin increase in breast cancer risk but the impact of this combined use on mammary gland homeostasis still needs evaluation.

  18. Breast Cancer (For Kids)

    Science.gov (United States)

    ... or sacs) or they can be due to normal breast changes associated with hormone changes or aging. Girls who are beginning puberty might notice a lump underneath the nipple when their breasts start developing. Usually, this is a normal. You can ask a parent or your doctor ...

  19. Breast reconstruction - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100156.htm Breast reconstruction - series—Indication, part 1 To use the sharing ... A.M. Editorial team. Related MedlinePlus Health Topics Breast Reconstruction A.D.A.M., Inc. is accredited by ...

  20. Hormone receptors in breast cancer

    NARCIS (Netherlands)

    Suijkerbuijk, K. P M; van der Wall, E.; van Diest, P. J.

    2016-01-01

    Steroid hormone receptors are critical for the growth and development of breast tissue as well as of breast cancer. The importance of the role estrogens in breast cancer has been delineated for more than 100 years. The analysis of its expression has been used not only to classify breast cancers but

  1. Breast Cancer and Bone Loss

    Science.gov (United States)

    ... Balance › Breast Cancer and Bone Loss Fact Sheet Breast Cancer and Bone Loss July, 2010 Download PDFs English ... JoAnn Pinkerton, MD What is the link between breast cancer and bone loss? Certain treatments for breast cancer ...

  2. Apoptosis and the thymic microenvironment in murine lupus.

    Science.gov (United States)

    Takeoka, Y; Taguchi, N; Shultz, L; Boyd, R L; Naiki, M; Ansari, A A; Gershwin, M E

    1999-11-01

    The thymus of New Zealand black (NZB) mice undergoes premature involution. In addition, cultured thymic epithelial cells from NZB mice undergo accelerated preprogrammed degeneration. NZB mice also have distinctive and well-defined abnormalities of thymic architecture involving stromal cells, defined by staining with monoclonal antibodies specific for the thymic microenvironment. We took advantage of these findings, as well as our large panel of monoclonal antibodies which recognize thymic stroma, to study the induction of apoptosis in the thymus of murine lupus and including changes of epithelial architecture. We studied NZB, MRL/lpr, BXSB/Yaa, C3H/gld mice and BALB/c and C57BL/6 as control mice. Apoptosis was studied both at basal levels and following induction with either dexamethasone or lipopolysaccharide (LPS). The apoptotic cells were primarily found in the thymic cortex, and the frequency of apoptosis in murine lupus was less than 20% of controls. Moreover, all strains of murine lupus had severe abnormalities of the cortical network. These changes were not accentuated by dexamethasone treatment in cultured thymocytes. However, the thymus in murine lupus was less susceptible to LPS-induced apoptosis than control mice. Finally we note that the number of thymic nurse cells (TNC) was lowest in NZB mice. Our findings demonstrate significant abnormalities in the induction of apoptosis and the formation of TNC-like epithelial cells in SLE mice, and suggest that the abnormalities of the thymic microenvironment have an important role in the pathogenesis of murine lupus.

  3. Isotype specific immune responses in murine experimental toxocariasis

    Directory of Open Access Journals (Sweden)

    Cuéllar C

    2001-01-01

    Full Text Available In this work, a murine experimental model of toxocariasis has been developed in BALB/c, C57BL/10 and C3H murine strains orally inoculated with 4,000 Toxocara canis embryonated eggs, in order to investigate the isotype-specific immune responses against excretory-secretory antigens from larvae. T. canis specific IgG+M, IgM, IgG, IgA, IgG1, IgG2a and IgG3 were tested by ELISA. The dynamics of the specific immunoglobulins (IgG+IgM production showed a contrasting profile regarding the murine strain. Conversely to the results obtained with the IgM isotype, the IgG antibody class showed similar patterns to those obtained with IgG+IgM antibodies, only in the case of the BALB/c strain, being different and much higher than the obtained with IgG+IgM antibodies, when the C3H murine strain was used. The antibodies IgG+IgM tested in BALB/c and C57BL/10 were both of the IgM and IgG isotypes. Conversely, in the C3H strain only IgG specific antibody levels were detected. The IgG1 subclass responses showed a similar profile in the three murine strains studied, with high values in BALB/c, as in the case of the IgG responses.

  4. Murine Typhus: An Important Consideration for the Nonspecific Febrile Illness

    Directory of Open Access Journals (Sweden)

    Gurjot Basra

    2012-01-01

    Full Text Available Murine typhus is a widely distributed flea-borne infection caused by Rickettsia typhi. Symptoms of murine typhus are nonspecific and mimic a variety of other infectious diseases. We herein report a case of murine typhus in an area where the broad use of DDT in the mid-20th century has now made it a rare disease. The patient described presented with headache, fever, and a faint macular rash. Initial laboratory studies revealed a slight transaminase elevation. Further questioning revealed exposure to opossums, prompting the consideration of murine typhus as a diagnosis. Although typhus group antibodies were not present during the patient’s acute illness, empiric therapy with doxycycline was initiated, and the patient defervesced. One month after convalescence, the patient returned to clinic with serum that contained typhus group antibodies with an IgG titer of 1 : 1024. Murine typhus is an important consideration during the workup of a patient with a nonspecific febrile illness. Exposure to reservoir hosts and the flea vector place humans at risk for this disease. Clinician recognition of this entity is required for diagnosis and effective therapy.

  5. Analysis of cardiomyocyte movement in the developing murine heart

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Hisayuki [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan); Yuasa, Shinsuke, E-mail: yuasa@a8.keio.jp [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan); Tabata, Hidenori [Department of Anatomy, Keio University School of Medicine, Tokyo (Japan); Tohyama, Shugo; Seki, Tomohisa; Egashira, Toru; Hayashiji, Nozomi; Hattori, Fumiyuki; Kusumoto, Dai; Kunitomi, Akira; Takei, Makoto; Kashimura, Shin; Yozu, Gakuto; Shimojima, Masaya; Motoda, Chikaaki; Muraoka, Naoto [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan); Nakajima, Kazunori [Department of Anatomy, Keio University School of Medicine, Tokyo (Japan); Sakaue-Sawano, Asako; Miyawaki, Atsushi [Life Function and Dynamics, ERATO, JST, 2-1 Hirosawa, Wako-city, Saitama 351-0198 (Japan); Laboratory for Cell Function and Dynamics, Advanced Technology Development Group, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198 (Japan); Fukuda, Keiichi [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan)

    2015-09-04

    The precise assemblage of several types of cardiac precursors controls heart organogenesis. The cardiac precursors show dynamic movement during early development and then form the complicated heart structure. However, cardiomyocyte movements inside the newly organized mammalian heart remain unclear. We previously established the method of ex vivo time-lapse imaging of the murine heart to study cardiomyocyte behavior by using the Fucci (fluorescent ubiquitination-based cell cycle indicator) system, which can effectively label individual G1, S/G2/M, and G1/S-transition phase nuclei in living cardiomyocytes as red, green, and yellow, respectively. Global analysis of gene expression in Fucci green positive ventricular cardiomyocytes confirmed that cell cycle regulatory genes expressed in G1/S, S, G2/M, and M phase transitions were upregulated. Interestingly, pathway analysis revealed that many genes related to the cell cycle were significantly upregulated in the Fucci green positive ventricular cardiomyocytes, while only a small number of genes related to cell motility were upregulated. Time-lapse imaging showed that murine proliferating cardiomyocytes did not exhibit dynamic movement inside the heart, but stayed on site after entering the cell cycle. - Highlights: • We directly visualized cardiomyocyte movement inside the developing murine heart. • Cell cycle related genes were upregulated in the proliferating cardiomyocytes. • Time-lapse imaging revealed that proliferating murine cardiomyocytes stayed in place. • Murine ventricular cardiomyocytes proliferate on site during development.

  6. A novel agent exerts antitumor activity in breast cancer cells by targeting mitochondrial complex II

    Science.gov (United States)

    Cui, Guozhen; Chan, Judy Yuet-Wa; Wang, Li; Li, Chuwen; Shan, Luchen; Xu, Changjiang; Zhang, Qingwen; Wang, Yuqiang; Di, Lijun; Lee, Simon Ming-Yuen

    2016-01-01

    The mitochondrial respiratory chain, including mitochondrial complex II, has emerged as a potential target for cancer therapy. In the present study, a novel conjugate of danshensu (DSS) and tetramethylpyrazine (TMP), DT-010, was synthesized. Our results showed that DT-010 is more potent than its parental compounds separately or in combination, in inhibiting the proliferation of MCF-7 and MDA-MB-231 cells by inducing cytotoxicity and promoting cell cycle arrest. It also inhibited the growth of 4T1 breast cancer cells in vivo. DT-010 suppressed the fundamental parameters of mitochondrial function in MCF-7 cells, including basal respiration, ATP turnover, maximal respiration. Treatment with DT-010 in MCF-7 and MDA-MB-231 cells resulted in the loss of mitochondrial membrane potential and decreased ATP production. DT-010 also promoted ROS generation, while treatment with ROS scavenger, NAC (N-acetyl-L-cysteine), reversed DT-010-induced cytotoxicity. Further study showed that DT-010 suppressed succinate-induced mitochondrial respiration and impaired mitochondrial complex II enzyme activity indicating that DT-010 may inhibit mitochondrial complex II. Overall, our results suggested that the antitumor activity of DT-010 is associated with inhibition of mitochondrial complex II, which triggers ROS generation and mitochondrial dysfunction in breast cancer cells. PMID:27081033

  7. Gene expression profiling during murine tooth development

    Directory of Open Access Journals (Sweden)

    Maria A dos Santos silva Landin

    2012-07-01

    Full Text Available The aim of this study was to describe the expression of genes, including ameloblastin (Ambn, amelogenin X chromosome (Amelx and enamelin (Enam during early (pre-secretory tooth development. The expression of these genes has predominantly been studied at post-secretory stages. Deoxyoligonucleotide microarrays were used to study gene expression during development of the murine first molar tooth germ at 24h intervals, starting at the eleventh embryonic day (E11.5 and up to the seventh day after birth (P7. The profile search function of Spotfire software was used to select genes with similar expression profile as the enamel genes (Ambn, Amelx and Enam. Microarray results where validated using real-time Reverse Transcription-Polymerase Chain Reaction (real-time RT-PCR, and translated proteins identified by Western blotting. In situ localisation of the Ambn, Amelx and Enam mRNAs were monitored from E12.5 to E17.5 using deoxyoligonucleotide probes. Bioinformatics analysis was used to associate biological functions with differentially (p ≤0.05 expressed (DE genes.Microarray results showed a total of 4362 genes including Ambn, Amelx and Enam to be significant differentially expressed throughout the time-course. The expression of the three enamel genes was low at pre-natal stages (E11.5-P0 increasing after birth (P1-P7. Profile search lead to isolation of 87 genes with significantly similar expression to the three enamel proteins. The mRNAs expressed in dental epithelium and epithelium derived cells. Although expression of Ambn, Amelx and Enam were lower during early tooth development compared to secretory stages enamel proteins were detectable by Western blotting. Bioinformatic analysis associated the 87 genes with multiple biological functions. Around thirty-five genes were associated with fifteen transcription factors.

  8. Curcumin-loaded guanidine functionalized PEGylated I3ad mesoporous silica nanoparticles KIT-6: practical strategy for the breast cancer therapy.

    Science.gov (United States)

    Ma'mani, Leila; Nikzad, Safoora; Kheiri-Manjili, Hamidreza; Al-Musawi, Sharafaldin; Saeedi, Mina; Askarlou, Sonia; Foroumadi, Alireza; Shafiee, Abbas

    2014-08-18

    In this research, we have synthesized guanidine functionalized PEGylated mesoporous silica nanoparticles as a novel and efficient drug delivery system (DDS). For this purpose, guanidine functionalized PEGylated I3ad mesoporous silica nanoparticle KIT-6 [Gu@PEGylated KIT-6] was utilized as a promising system for the effective delivery of curcumin into the breast cancer cells. The modified mesoporous silica nanoparticles (MSNs) was fully characterized by different techniques such as transmission and scanning electron microscopy (TEM & SEM), N2 adsorption-desorption measurement, thermal gravimetric analysis (TGA), X-ray powder diffraction (XRD), and dynamic light scattering (DLS). The average particle size of [Gu@PEGylated KIT-6] and curcumin loaded [Gu@PEGylated KIT-6] nanoparticles were about 60 and 70 nm, respectively. This new system exhibited high drug loading capacity, sustained drug release profile, and high and long term anticancer efficacy in human cancer cell lines. It showed pH-responsive controlled characteristics and highly programmed release of curcumin leading to the satisfactory results in in vitro breast cancer therapy. Our results depicted that the pure nanoparticles have no cytotoxicity against human breast adenocarcinoma cells (MCF-7), mouse breast cancer cells (4T1), and human mammary epithelial cells (MCF10A).

  9. Molecular characterizations of Nop16 in murine mammary tumors with varying levels of c-Myc.

    Science.gov (United States)

    Kundel, Donald W; Stromquist, Emily; Greene, Amy L; Zhdankin, Olga; Regal, Ronald R; Rose-Hellekant, Teresa A

    2012-04-01

    NOP16, also known as HSPC111, has been identified as a MYC and estrogen regulated gene in in vitro studies, hence coexpression levels were strongly correlated. Importantly, high expression of NOP16 was associated with poor clinical outcome in breast cancer patients. However, coexpression of NOP16, MYC and estrogen receptor (ESR1) varied widely in tumors and cell lines suggesting that transcriptional regulation differed according to pathological environments. The goal of this study was to determine the expression patterns of Nop16, Myc and Esr1 in murine mammary tumors with disparate histopathological and molecular features. We hypothesized that tumor environments with relatively high Myc levels would have different coexpression patterns than tumor environments with relatively low Myc levels. We measured levels of Myc and Nop16 mRNA and protein in tumors from WAP-c-myc mice that were of high grade and metastasized frequently. In contrast, Myc and Nop16 mRNA and proteins levels were significantly lower in the less aggressive tumors that developed in NRL-TGFα mice. Tumors from both mouse lines express ESR1 protein and we found that Esr1 mRNA levels correlated positively with Myc levels in both models. However, Myc and Nop16 transcript levels correlated positively only in tumors from NRL-TGFα mice. We identified prominent NOP16 protein in nuclei and less prominent staining in the cytoplasm of luminal cells of ducts and lobules from normal mammary glands as well as in hyperplasias and tumors obtained from NRL-TGFα mice. This staining pattern was reversed in tumors from WAP-c-Myc mice as nuclear staining was faint or absent and cytoplasmic staining more pronounced. In summary, the regulation of expression and localization of NOP16 varies in tumor environments with high versus low MYC levels and demonstrate the importance of stratifying clinical breast cancers based on MYC levels.

  10. Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis

    Science.gov (United States)

    Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

    2009-01-01

    Introduction Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. Methods To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. Results We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor

  11. Oncoplastic breast surgery in Denmark

    DEFF Research Database (Denmark)

    Klit, Anders; Henriksen, Trine Foged; Siersen, Hans Erik

    2014-01-01

    With improved survival rates after breast cancer treatment, more attention is drawn to improve the cosmetic outcome after surgical treatment of breast cancer. In this process the oncoplastic breast surgery was conceived. It supplements the traditional surgical treatments (mastectomy and breast...... conserving surgery) with increased focus on individualized therapy. The ambition is to obtain the best possible cosmetic outcome without compromising recurrence rates and survival. This article provides an overview of the current oncoplastic breast surgery treatment offered in Denmark....

  12. The characterization of breast anatomical metrics using dedicated breast CT

    Science.gov (United States)

    Huang, Shih-Ying; Boone, John M.; Yang, Kai; Packard, Nathan J.; McKenney, Sarah E.; Prionas, Nicolas D.; Lindfors, Karen K.; Yaffe, Martin J.

    2011-01-01

    Purpose: Accurate anatomical characterization of the breast is useful in breast phantom development and computer modeling of breast imaging technologies. Capitalizing on the three-dimensional capabilities of dedicated breast CT (bCT), a number of parameters which describe breast shape and fibroglandular distribution are defined. Methods: Among 219 bCT data sets, the effective diameter and length of the pendant breast as well as the breast volume were measured and characterized for each bra cup size. The volume glandular fraction (VGF) was determined as a function of patient age, BIRADS density, bra cup size, and breast diameter. The glandular fraction was examined in coronal and sagittal planes of the breast, and the radial distribution of breast glandular fraction within a coronal bCT image was examined for three breast regions. The areal glandular fraction (AGF) was estimated from two-dimensional projections of the breast (simulated by projecting bCT data sets) and was compared to the corresponding VGF. Results: The effective breast diameter and length increase with increasing bra cup size. The mean breast diameters (± standard error) of bra cup sizes A∕AA, B, C, and D∕DD were 11.1±0.5, 11.4±0.3, 13.0±0.2, and 13.7±0.2 cm, respectively. VGF was lower among older women and those with larger breast diameter and larger bra cup size. VGF increased as a function of the reported BIRADS density. AGF increased with VGF. Fibroglandular tissue was distributed primarily in the central portion of the breast. Conclusions: Breast metrics were examined and a number of parameters were defined which may be useful for breast modeling. The reported data may provide researchers with useful information for characterizing the breast for various imaging or dosimetry tasks. PMID:21626952

  13. Intensity Modulated Accelerated Partial Breast Irradiation Before Surgery in Treating Older Patients With Hormone Responsive Stage 0-I Breast Cancer

    Science.gov (United States)

    2016-05-04

    Ductal Breast Carcinoma in Situ; Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Ductal Breast Carcinoma With Predominant Intraductal Component; Lobular Breast Carcinoma in Situ; Medullary Ductal Breast Carcinoma With Lymphocytic Infiltrate; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Progesterone Receptor-positive Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Tubular Ductal Breast Carcinoma

  14. Herpesviruses and breast milk

    Directory of Open Access Journals (Sweden)

    C. Pietrasanta

    2014-06-01

    Full Text Available Breast milk has always been the best source of nourishment for newborns. However, breast milk can carry a risk of infection, as it can be contaminated with bacterial or viral pathogens. This paper reviews the risk of acquisition of varicella-zoster virus (VZV and cytomegalovirus (CMV, herpesviruses frequently detected in breastfeeding mothers, via breast milk, focusing on the clinical consequences of this transmission and the possible strategies for preventing it. Maternal VZV infections are conditions during which breastfeeding may be temporarily contraindicated, but expressed breast milk should always be given to the infant. CMV infection acquired through breast milk rarely causes disease in healthy term newborns; an increased risk of CMV disease has been documented in preterm infants. However, the American Academy of Pediatrics (AAP does not regard maternal CMV seropositivity as a contraindication to breastfeeding; according to the AAP, in newborns weighing less than 1500 g, the decision should be taken after weighing the benefits of breast milk against the risk of transmission of infection. The real efficacy of the different methods of inactivating CMV in breast milk should be compared in controlled clinical trials, rigorously examining the negative consequences that each of these methods can have on the immunological and nutritional properties of the milk itself, with a view to establish the best risk-benefit ratio of these strategies before they are recommended for use in clinical practice.

  15. Breast feeding in IMD.

    Science.gov (United States)

    MacDonald, A; Depondt, E; Evans, S; Daly, A; Hendriksz, C; Chakrapani A, A; Saudubray, J-M

    2006-01-01

    Breast feeding has proven benefits for many infants with inherited metabolic disorders (IMDs) but, with the exception of phenylketonuria, there are few reports in other conditions. A questionnaire, completed by dietitians and clinicians from 27 IMD centres from 15 countries (caring for a total of over 8000 patients with IMDs on diet) identified breast feeding experience in IMD. Successful, demand breast feeding (in combination with an infant amino acid formula free of precursor amino acids) was reported in 17 infants with MSUD, 14 with tyrosinaemia type I, and 5 with homocystinuria. Eighty-nine per cent were still breast fed at 16 weeks. Fewer infants with organic acidaemias were demand breast fed (7 with propionic acidaemia; 6 with methylmalonic acidaemia and 13 with isovaleric acidaemia) (usually preceded by complementary feeds of a protein-free infant formula or infant amino acid formula free of precursor amino acids). Only 12 infants with urea cycle disorders were given demand breast feeds, but this was unsuccessful beyond 8 days in CPS deficiency. Further work is needed in developing guidelines for feeding and for clinical and biochemical monitoring for breast-fed infants with IMDs.

  16. A rapid murine coma and behavior scale for quantitative assessment of murine cerebral malaria.

    Directory of Open Access Journals (Sweden)

    Ryan W Carroll

    Full Text Available BACKGROUND: Cerebral malaria (CM is a neurological syndrome that includes coma and seizures following malaria parasite infection. The pathophysiology is not fully understood and cannot be accounted for by infection alone: patients still succumb to CM, even if the underlying parasite infection has resolved. To that effect, there is no known adjuvant therapy for CM. Current murine CM (MCM models do not allow for rapid clinical identification of affected animals following infection. An animal model that more closely mimics the clinical features of human CM would be helpful in elucidating potential mechanisms of disease pathogenesis and evaluating new adjuvant therapies. METHODOLOGY/PRINCIPAL FINDINGS: A quantitative, rapid murine coma and behavior scale (RMCBS comprised of 10 parameters was developed to assess MCM manifested in C57BL/6 mice infected with Plasmodium berghei ANKA (PbA. Using this method a single mouse can be completely assessed within 3 minutes. The RMCBS enables the operator to follow the evolution of the clinical syndrome, validated here by correlations with intracerebral hemorrhages. It provides a tool by which subjects can be identified as symptomatic prior to the initiation of trial treatment. CONCLUSIONS/SIGNIFICANCE: Since the RMCBS enables an operator to rapidly follow the course of disease, label a subject as affected or not, and correlate the level of illness with neuropathologic injury, it can ultimately be used to guide the initiation of treatment after the onset of cerebral disease (thus emulating the situation in the field. The RMCBS is a tool by which an adjuvant therapy can be objectively assessed.

  17. Radio-adjuvant effects of ginsan on murine breast carcinoma xenografted model

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Ji Young; Son, Hyeog Jin; Kim, Hyung Doo; Han, Young Soo; Yun, Yeon Sook; Song, Jie Young [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2005-07-01

    In a number of studies, polysaccharide extracted from Panax ginseng C.A. Meyer, ginsan has been demonstrated to be a potent promising biological response modifier (BRM), including proliferation of lymphocyte, generation of lymphokine activated killer cells, and production of several cytokines. Macrophages are the first line of defense to infections or pathogens in host innate immunity. In addition, it plays a prominent role as a professional antigen presenting cells to trigger cellular immunity. In the light of that, the current study was designed to evaluate whether ginsan exhibits anti-tumor effect as well as synergistic function with chemo- or radio-therapy.

  18. Isoforms of murine and human serum amyloid P component

    DEFF Research Database (Denmark)

    Nybo, Mads; Hackler, R; Kold, B

    1998-01-01

    Isoelectric focusing (IEF) and immunofixation of murine serum amyloid P component (SAP), purified and in serum, showed a distinct and strain-dependent isoform pattern with up to seven bands (pI 5.1-5.7). Neuraminidase treatment caused a shift of the isoforms to more basic pI values, but did...... of isoforms of human SAP required the presence of urea and higher SAP concentrations. TEF and immunofixation of SAP monomers showed five to eight isoforms, ranging from pI 4.7-5.7. IEF of SAP in human serum resulted in a less distinct pattern and more acidic isoforms. As with murine SAP, neuraminidase...

  19. CDDO-Me Redirects Activation of Breast Tumor Associated Macrophages.

    Directory of Open Access Journals (Sweden)

    Michael S Ball

    Full Text Available Tumor-associated macrophages can account for up to 50% of the tumor mass in breast cancer patients and high TAM density is associated with poor clinical prognosis. Because TAMs enhance tumor growth, development, and metastatic potential, redirection of TAM activation may have significant therapeutic benefit. Our studies in primary human macrophages and murine breast TAMs suggest that the synthetic oleanane triterpenoid CDDO-methyl ester (CDDO-Me reprograms the activation profile of TAMs from tumor-promoting to tumor-inhibiting. We show that CDDO-Me treatment inhibits expression of IL-10 and VEGF in stimulated human M2 macrophages and TAMs but increases expression of TNF-α and IL-6. Surface expression of CD206 and CD163, which are characteristic of M2 activation, is significantly attenuated by CDDO-Me. In contrast, CDDO-Me up-regulates surface expression of HLA-DR and CD80, which are markers of M1 activation, and importantly potentiates macrophage activation of autologous T cells but inhibits endothelial cell vascularization. These results show for the first time that CDDO-Me redirects activation of M2 macrophages and TAMs from immune-suppressive to immune-stimulatory, and implicate a role for CDDO-Me as an immunotherapeutic in the treatment of breast and potentially other types of cancer.

  20. Why Are My Breasts Sore? (For Teens)

    Science.gov (United States)

    ... sure? Why Do I Have Breasts Anyway? All mammals have breasts and humans are no exception. Breasts, ... Ache? Most PMS symptoms, including breast soreness, should disappear as your period begins. Over-the-counter pain ...

  1. Partial breast radiation therapy - external beam

    Science.gov (United States)

    ... include: Breast redness, tenderness, sensitivity Breast swelling or edema Breast infection (rare) Long-term side effects may begin months or years after treatment and may include: Decreased breast size Increased firmness ...

  2. Mutational dynamics of murine angiogenin duplicates

    Directory of Open Access Journals (Sweden)

    Fares Mario A

    2010-10-01

    Full Text Available Abstract Background Angiogenin (Ang is a protein involved in angiogenesis by inducing the formation of blood vessels. The biomedical importance of this protein has come from findings linking mutations in Ang to cancer progression and neurodegenerative diseases. These findings highlight the evolutionary constrain on Ang amino acid sequence. However, previous studies comparing human Angiogenin with homologs from other phylogenetically related organisms have led to the conclusion that Ang presents a striking variability. Whether this variability has an adaptive value per se remains elusive. Understanding why many functional Ang paralogs have been preserved in mouse and rat and identifying functional divergence mutations at these copies may explain the relationship between mutations and function. In spite of the importance of testing this hypothesis from the evolutionarily and biomedical perspectives, this remains yet unaccomplished. Here we test the main mutational dynamics driving the evolution and function of Ang paralogs in mammals. Results We analysed the phylogenetic asymmetries between the different Ang gene copies in mouse and rat in the context of vertebrate Ang phylogeny. This analysis shows strong evidence in support of accelerated evolution in some Ang murine copies (mAng. This acceleration is not due to non-functionalisation because constraints on amino acid replacements remain strong. We identify many of the amino acid sites involved in signal localization and nucleotide binding by Ang to have evolved under diversifying selection. Compensatory effects of many of the mutations at these paralogs and their key structural location in or nearby important functional regions support a possible functional shift (functional divergence in many Ang copies. Similarities between 3D-structural models for mAng copies suggest that their divergence is mainly functional. Conclusions We identify the main evolutionary dynamics shaping the variability of

  3. Nanoelectroablation therapy for murine basal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nuccitelli, Richard, E-mail: rich@bioelectromed.com [BioElectroMed Corp., 849 Mitten Rd., Suite 104, Burlingame, CA 94010 (United States); Tran, Kevin; Athos, Brian; Kreis, Mark; Nuccitelli, Pamela [BioElectroMed Corp., 849 Mitten Rd., Suite 104, Burlingame, CA 94010 (United States); Chang, Kris S.; Epstein, Ervin H. [The Children' s Hospital Oakland Research Institute, Oakland, CA 94609 (United States); Tang, Jean Y. [The Children' s Hospital Oakland Research Institute, Oakland, CA 94609 (United States); Stanford University, Stanford, CA 94305 (United States)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer Nanoelectroablation is a new, non-thermal therapy that triggers apoptosis in tumors. Black-Right-Pointing-Pointer Low energy, ultrashort, high voltage pulses ablate the tumor with little or no scar. Black-Right-Pointing-Pointer Nanoelectroablation eliminates 99.8% of the BCC but may leave a few remnants behind. Black-Right-Pointing-Pointer Pilot clinical trials on human BCCs are ongoing and leave no remnants in most cases. -- Abstract: When skin tumors are exposed to non-thermal, low energy, nanosecond pulsed electric fields (nsPEF), apoptosis is initiated both in vitro and in vivo. This nanoelectroablation therapy has already been proven effective in treating subdermal murine allograft tumors. We wanted to determine if this therapy would be equally effective in the treatment of autochthonous BCC tumors in Ptch1{sup +/-}K14-Cre-ER p53 fl/fl mice. These tumors are similar to human BCCs in histology and in response to drug therapy . We have treated 27 BCCs across 8 mice with either 300 pulses of 300 ns duration or 2700 pulses of 100 ns duration, all at 30 kV/cm and 5-7 pulses per second. Every nsPEF-treated BCC began to shrink within a day after treatment and their initial mean volume of 36 {+-} 5 (SEM) mm{sup 3} shrunk by 76 {+-} 3% over the ensuing two weeks. After four weeks, they were 99.8% ablated if the size of the treatment electrode matched the tumor size. If the tumor was larger than the 4 mm wide electrode, multiple treatments were needed for complete ablation. Treated tumors were harvested for histological analysis at various times after treatment and exhibited apoptosis markers. Specifically, pyknosis of nuclei was evident as soon as 2 days after nsPEF treatment, and DNA fragmentation as detected via TUNEL staining was also evident post treatment. Nanoelectroablation is effective in triggering apoptosis and remission of radiation-induced BCCs with a single 6 min-long treatment of 2700 pulses.

  4. Breast MRI: guidelines from the European Society of Breast Imaging

    OpenAIRE

    Mann, R. M.; Kuhl, C. K.; Kinkel, K.; BOETES, C.

    2008-01-01

    The aim of breast MRI is to obtain a reliable evaluation of any lesion within the breast. It is currently always used as an adjunct to the standard diagnostic procedures of the breast, i.e., clinical examination, mammography and ultrasound. Whereas the sensitivity of breast MRI is usually very high, specificity—as in all breast imaging modalities—depends on many factors such as reader expertise, use of adequate techniques and composition of the patient cohorts. Since breast MRI will always yi...

  5. Directed evolution and targeted mutagenesis to murinize listeria monocytogenes internalin A for enhanced infectivity in the murine oral infection model

    Directory of Open Access Journals (Sweden)

    Hill Colin

    2010-12-01

    Full Text Available Abstract Background Internalin A (InlA is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells. Results We have created a surface display library of randomly mutated InlA in a non-invasive heterologous host Lactococcus lactis in order to create and screen novel variants of this invasion factor. After sequential passage through a murine cell line (CT-26, multiple clones with enhanced invasion characteristics were identified. Competitive index experiments were conducted in mice using selected mutations introduced into L. monocytogenes EGD-e background. A novel single amino acid change was identified which enhanced virulence by the oral route in the murine model and will form the basis of further engineering approaches. As a control a previously described EGD-InlAm murinized strain was also re-created as part of this study with minor modifications and designated EGD-e InlAm*. The strain was created using a procedure that minimizes the likelihood of secondary mutations and incorporates Listeria-optimized codons encoding the altered amino acids. L. monocytogenes EGD-e InlAm* yielded consistently higher level murine infections by the oral route when compared to EGD-e, but did not display the two-fold increased invasion into a human cell line that was previously described for the EGD-InlAm strain. Conclusions We have used both site-directed mutagenesis and directed evolution to create variants of InlA which may inform future structure-function analyses of this protein. During the course of the study we engineered a murinized strain of L. monocytogenes EGD-e which shows reproducibly higher infectivity in the intragastric murine infection model than the wild type, but does not display enhanced

  6. Directed evolution and targeted mutagenesis to murinize Listeria monocytogenes Internalin A for enhanced infectivity in the murine oral infection model

    LENUS (Irish Health Repository)

    Monk, Ian R

    2010-12-13

    Abstract Background Internalin A (InlA) is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells. Results We have created a surface display library of randomly mutated InlA in a non-invasive heterologous host Lactococcus lactis in order to create and screen novel variants of this invasion factor. After sequential passage through a murine cell line (CT-26), multiple clones with enhanced invasion characteristics were identified. Competitive index experiments were conducted in mice using selected mutations introduced into L. monocytogenes EGD-e background. A novel single amino acid change was identified which enhanced virulence by the oral route in the murine model and will form the basis of further engineering approaches. As a control a previously described EGD-InlAm murinized strain was also re-created as part of this study with minor modifications and designated EGD-e InlA m*. The strain was created using a procedure that minimizes the likelihood of secondary mutations and incorporates Listeria-optimized codons encoding the altered amino acids. L. monocytogenes EGD-e InlA m* yielded consistently higher level murine infections by the oral route when compared to EGD-e, but did not display the two-fold increased invasion into a human cell line that was previously described for the EGD-InlAm strain. Conclusions We have used both site-directed mutagenesis and directed evolution to create variants of InlA which may inform future structure-function analyses of this protein. During the course of the study we engineered a murinized strain of L. monocytogenes EGD-e which shows reproducibly higher infectivity in the intragastric murine infection model than the wild type, but does not display enhanced entry into human

  7. Breast Reconstruction After Mastectomy

    Science.gov (United States)

    ... It also does not involve cutting of the abdominal muscle and is a free flap. This type of ... NCI fact sheet Mammograms . What are some new developments in breast reconstruction after mastectomy? Oncoplastic surgery. In ...

  8. Living Beyond Breast Cancer

    Science.gov (United States)

    ... Styles Common Yoga Poses Special Situations Yoga and Lymphedema Risk Yoga and Metastatic Breast Cancer Side Effects ... Insomnia and Fatigue Treatment for Insomnia and Fatigue Lymphedema Lymphedema Risk Treating Lymphedema Menopausal Symptoms Mouth Sores ...

  9. Fibrocystic breast disease

    Science.gov (United States)

    ... type of lump is common with fibrocystic breasts. Exams and Tests Your health care provider will examine ... bra Some women believe that eating less fat, caffeine, or chocolate helps with their symptoms. There is ...

  10. Recurrent Breast Cancer

    Science.gov (United States)

    ... that can help you cope with distress include: Art therapy Dance or movement therapy Exercise Meditation Music ... mayoclinic.org/diseases-conditions/recurrent-breast-cancer/basics/definition/CON-20032432 . Mayo Clinic Footer Legal Conditions and ...

  11. Premenstrual breast changes

    Science.gov (United States)

    ... org/docs/3091546/Narrative/ . Accessed July 15, 2016. Katz VL, Dotters D. Breast diseases: diagnosis and treatment ... disease. In: Lentz GM, Lobo RA, Gershenson DM, Katz VL, eds. Comprehensive Gynecology . 6th ed. Philadelphia, PA: ...

  12. Breast carcinoma metastases.

    Science.gov (United States)

    Bodzin, G A; Staren, E D; Faber, L P

    1998-02-01

    With careful selection of patients, complete resection of pulmonary metastases from breast carcinoma may be a useful therapeutic option. Such a treatment appears to offer a significant survival benefit when compared with medical treatment alone, or with incomplete resection.

  13. Inflammatory Breast Cancer

    Science.gov (United States)

    ... Other Funding Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training at ... means they developed from cells that line the milk ducts of the breast and then spread beyond ...

  14. Benign Breast Conditions

    Science.gov (United States)

    ... enlarge and feel tender right before your period.Fibroadenomas. These are the most common breast lumps in ... like, thick tissue, or a fluid-filled cyst.Fibroadenomas: This will feel like a small, round, moving ...

  15. Preeclampsia and breast cancer

    DEFF Research Database (Denmark)

    Pacheco, Nadja Livia Pekkola; Andersen, Anne-Marie Nybo; Kamper-Jørgensen, Mads

    2015-01-01

    BACKGROUND: In parous women preeclampsia has been associated with reduced risk of developing breast cancer. Characteristics of births following preeclamptic pregnancies may help understand mechanisms involved in the breast cancer risk reduction inferred by preeclampsia. METHODS: We conducted...... a register-based cohort study of all Danish women giving birth during 1978-2010 (n = 778,701). The association between preeclampsia and breast cancer was evaluated overall and according to birth characteristics by means of incidence rate ratios (IRR) estimated in Poisson regression models. RESULTS: Compared......, and in women giving birth to boys. These findings, however, did not reach statistical significance. Finally, risk reduction was slightly greater following milder forms of preeclampsia. CONCLUSION: Our data is compatible with an approximately 20% reduction in risk of developing breast cancer following...

  16. Risks of Breast Implants

    Science.gov (United States)

    ... an infection or injury. Demonstrated by redness, swelling, warmth, pain and or/loss of function. Lymphedema or ... Overfilling or underfilling of saline-filled breast implants Physical stresses such as trauma or intense physical pressure ...

  17. Contralateral breast cancer

    African Journals Online (AJOL)

    Department of Surgery, Ahmadu Bello University Teaching Hospital, Kaduna, Nigeria ... This second breast cancer remains, however largely sub-clinical. .... therapeutic mastectomy and prophylactic ... basis against the operation's physical and.

  18. Microwave Breast Imaging Techniques

    DEFF Research Database (Denmark)

    Zhurbenko, Vitaliy; Rubæk, Tonny

    2010-01-01

    This paper outlines the applicability of microwave radiation for breast cancer detection. Microwave imaging systems are categorized based on their hardware architecture. The advantages and disadvantages of various imaging techniques are discussed. The fundamental tradeoffs are indicated between v...

  19. Microwave Breast Imaging Techniques

    DEFF Research Database (Denmark)

    Zhurbenko, Vitaliy; Rubæk, Tonny

    2010-01-01

    This paper outlines the applicability of microwave radiation for breast cancer detection. Microwave imaging systems are categorized based on their hardware architecture. The advantages and disadvantages of various imaging techniques are discussed. The fundamental tradeoffs are indicated between...

  20. The evolving breast reconstruction

    DEFF Research Database (Denmark)

    Thomsen, Jørn Bo; Gunnarsson, Gudjon Leifur

    2014-01-01

    The aim of this editorial is to give an update on the use of the propeller thoracodorsal artery perforator flap (TAP/TDAP-flap) within the field of breast reconstruction. The TAP-flap can be dissected by a combined use of a monopolar cautery and a scalpel. Microsurgical instruments are generally...... not needed. The propeller TAP-flap can be designed in different ways, three of these have been published: (I) an oblique upwards design; (II) a horizontal design; (III) an oblique downward design. The latissimus dorsi-flap is a good and reliable option for breast reconstruction, but has been criticized...... for oncoplastic and reconstructive breast surgery and will certainly become an invaluable addition to breast reconstructive methods....

  1. Hormones and Breast Cancer.

    Science.gov (United States)

    1997-10-01

    criteria were: having ever been treated with chemotherapy, or been diagnosed with systemic lupus erythematosus or liver cirrhosis; having smoked the previous...history of breast cancer) was not associated with increased risk of breast cancer. Moreover, OC use before age 25 or first pregnancy was not...radioimmunoassay of unconjugated estriol in Endocrinol Metab 65:792-795 (1987). pregnancy plasma. Steroids 24:225-238 (1974). 47. Longcope C, Gorbach S

  2. Targeting Breast Cancer Metastasis

    OpenAIRE

    2015-01-01

    Metastasis is the leading cause of breast cancer-associated deaths. Despite the significant improvement in current therapies in extending patient life, 30–40% of patients may eventually suffer from distant relapse and succumb to the disease. Consequently, a deeper understanding of the metastasis biology is key to developing better treatment strategies and achieving long-lasting therapeutic efficacies against breast cancer. This review covers recent breakthroughs in the discovery of various me...

  3. Phantom breast syndrome

    Directory of Open Access Journals (Sweden)

    Ramesh

    2009-01-01

    Full Text Available Phantom breast syndrome is a type of condition in which patients have a sensation of residual breast tissue and can include both non-painful sensations as well as phantom breast pain. The incidence varies in different studies, ranging from approximately 30% to as high as 80% of patients after mastectomy. It seriously affects quality of life through the combined impact of physical disability and emotional distress. The breast cancer incidence rate in India as well as Western countries has risen in recent years while survival rates have improved; this has effectively increased the number of women for whom post-treatment quality of life is important. In this context, chronic pain following treatment for breast cancer surgery is a significantly under-recognized and under-treated problem. Various types of chronic neuropathic pain may arise following breast cancer surgery due to surgical trauma. The cause of these syndromes is damage to various nerves during surgery. There are a number of assumed factors causing or perpetuating persistent neuropathic pain after breast cancer surgery. Most well-established risk factors for developing phantom breast pain and other related neuropathic pain syndromes are severe acute postoperative pain and greater postoperative use of analgesics. Based upon current evidence, the goals of prophylactic strategies could first target optimal peri-operative pain control and minimizing damage to nerves during surgery. There is some evidence that chronic pain and sensory abnormalities do decrease over time. The main group of oral medications studied includes anti-depressants, anticonvulsants, opioids, N-methyl-D-asparate receptor antagonists, mexilitine, topical lidocaine, cannabinoids, topical capsaicin and glysine antagonists. Neuromodulation techniques such as motor cortex stimulation, spinal cord stimulation, and intrathecal drug therapies have been used to treat various neuropathic pain syndromes.

  4. Immunohistochemical diagnosis of systemic bovine zygomycosis by murine monoclonal antibodies

    DEFF Research Database (Denmark)

    Jensen, H.E.; Aalbaek, B.; Lind, Peter

    1996-01-01

    Murine monoclonal antibodies (Mabs) against water-soluble somatic antigens (WSSA) and the wall fraction (WF) from Rhizopus arrhizus (Rhizopus oryzae) were produced in vitro by fusion of splenocytes from immunized BALB/c mice with mouse myeloma X63-Ag 8.653 cells. Supernatants reacting only with h...... for the in situ diagnosis of systemic bovine zygomycosis....

  5. Increased rejection of murine allogeneic bone marrow in presensitized recipients

    NARCIS (Netherlands)

    vanOs, R; deWitte, T; Dillingh, JH; Mauch, PM; Down, JD

    1997-01-01

    The role of presensitizing murine recipients with donor spleen cells prior to T cell-depleted or -repleted H-2 compatible allogeneic bone marrow transplantation (BMT) was investigated at two different doses of total body irradiation (TBI). Recipients that were presensitized with 2 x 10(7) irradiated

  6. Murine Sirt3 protein isoforms have variable half-lives

    Science.gov (United States)

    Sirt3 is a NAD+-dependent protein deacetylase mainly localized in mitochondria. Recent studies indicate that the murine Sirt3 gene expresses different transcript variants resulting in three possible Sirt3 protein isoforms with variable lengths at the N-terminus: M1 (aa 1-334), M2 (aa 15-334), and M3...

  7. Macropinocytosis is the Entry Mechanism of Amphotropic Murine Leukemia Virus

    DEFF Research Database (Denmark)

    Rasmussen, Izabela; Vilhardt, Frederik

    2015-01-01

    The entry mechanism of murine amphotropic retrovirus (A-MLV) has not been unambiguously determined. We show here that A-MLV does not internalize by caveolae or other pinocytic mechanism, but by macropinocytosis. Thus A-MLV infection of mouse embryonic fibroblasts deficient for caveolin or dynamin...

  8. Pharmacodynamics of Doxycycline in a Murine Malaria Model▿

    OpenAIRE

    Batty, Kevin T.; Law, Angela S. F.; Stirling, Verity; Moore, Brioni R.

    2007-01-01

    Doxycycline is reported to impair second-generation parasite schizogony. The effects of doxycycline alone and combined with dihydroartemisinin were investigated in a murine malaria model. Doxycycline lowered the rate of parasite growth within 2 days, with maximum effect in 6 days. Addition of dihydroartemisinin led to an additive antimalarial effect.

  9. Turnover of T cells in murine gammaherpesvirus 68-infected mice

    DEFF Research Database (Denmark)

    Hamilton-Easton, A M; Christensen, Jan Pravsgaard; Doherty, P C

    1999-01-01

    Respiratory challenge of C57BL/6 mice with murine gammaherpesvirus 68 induces proliferation of T lymphocytes early after infection, as evidenced by incorporation of the DNA precursor bromodeoxyuridine. Using pulse-chase analysis, splenic and peripheral blood activated T lymphocytes were found...

  10. Immunotherapy of hepatoma with a monoclonal antibody against murine endoglin

    Institute of Scientific and Technical Information of China (English)

    Guang-Hong Tan; Feng-Ying Huang; Hua Wang; Yong-Hao Huang; Ying-Ying Lin; Yue-Nan Li

    2007-01-01

    AIM: To explore the capability of a monoclonal antibody(mAb) against murine endoglin to inhibit tumor angiogenesis and suppression of hepatoma growth in murine models.METHODS: A monoclonal antibody against murine endoglin was purified by affinity chromatography and passively transfused through tail veins in two murine hepatoma models. Tumor volume and survival time were observed at three-day intervals for 48 d. Microvessels in tumor tissues were detected by immunohistochemistry against CD31, and angiogenesis in vivo was determined by alginate encapsulated assay. In addition, tumor cell apoptosis was detected by TUNEL assay.RESULTS: Passive immunotherapy with anti-endoglin mAb could effectively suppress tumor growth, and prolonged the survival time of hepatoma-bearing mice.Angiogenesis was apparently inhibited within the tumor tissues, and the vascularization of alginate beads was also reduced in the mice passively transfused with antiendoglin mAb. In addition, increased apoptotic cells were observed within the tumor tissues from the mice passively transfused with anti-endoglin mAb.CONCLUSION: Passive immunotherapy with antiendoglin mAb effectively inhibits tumor growth via inhibiting tumor angiogenesis and increasing tumor cell apoptosis, which may be highly correlated with the blockage of endoglin-related signal pathway induced by anti-endoglin mAb.

  11. Expression of biologically active murine interleukin-18 in Lactococcus lactis.

    Science.gov (United States)

    Feizollahzadeh, Sadegh; Khanahmad, Hossein; Rahimmanesh, Ilnaz; Ganjalikhani-Hakemi, Mazdak; Andalib, Alireza; Sanei, Mohammad Hossein; Rezaei, Abbas

    2016-11-01

    The food-grade bacterium Lactococcus lactis is increasingly used for heterologous protein expression in therapeutic and industrial applications. The ability of L. lactis to secrete biologically active cytokines may be used for the generation of therapeutic cytokines. Interleukin (IL)-18 enhances the immune response, especially on mucosal surfaces, emphasizing its therapeutic potential. However, it is produced as an inactive precursor and has to be enzymatically cleaved for maturation. We genetically manipulated L. lactis to secrete murine IL-18. The mature murine IL-18 gene was inserted downstream of a nisin promoter in pNZ8149 plasmid and the construct was used to transform L. lactis NZ3900. The transformants were selected on Elliker agar and confirmed by restriction enzyme digestion and sequencing. The expression and secretion of IL-18 protein was verified by SDS-PAGE, western blotting and ELISA. The biological activity of recombinant IL-18 was determined by its ability to induce interferon (IFN)-γ production in L. lactis co-cultured with murine splenic T cells. The amounts of IL-18 in bacterial lysates and supernatants were 3-4 μg mL(-1) and 0.6-0.7 ng mL(-1), respectively. The successfully generated L. lactis strain that expressed biologically active murine IL-18 can be used to evaluate the possible therapeutic effects of IL-18 on mucosal surfaces.

  12. ALDH1-positive cancer stem cells predict engraftment of primary breast tumors and are governed by a common stem cell program.

    Science.gov (United States)

    Charafe-Jauffret, Emmanuelle; Ginestier, Christophe; Bertucci, François; Cabaud, Olivier; Wicinski, Julien; Finetti, Pascal; Josselin, Emmanuelle; Adelaide, José; Nguyen, Tien-Tuan; Monville, Florence; Jacquemier, Jocelyne; Thomassin-Piana, Jeanne; Pinna, Guillaume; Jalaguier, Aurélie; Lambaudie, Eric; Houvenaeghel, Gilles; Xerri, Luc; Harel-Bellan, Annick; Chaffanet, Max; Viens, Patrice; Birnbaum, Daniel

    2013-12-15

    Cancer stem-like cells (CSC) have been widely studied, but their clinical relevance has yet to be established in breast cancer. Here, we report the establishment of primary breast tumor-derived xenografts (PDX) that encompass the main diversity of human breast cancer and retain the major clinicopathologic features of primary tumors. Successful engraftment was correlated with the presence of ALDH1-positive CSCs, which predicted prognosis in patients. The xenografts we developed showed a hierarchical cell organization of breast cancer with the ALDH1-positive CSCs constituting the tumorigenic cell population. Analysis of gene expression from functionally validated CSCs yielded a breast CSC signature and identified a core transcriptional program of 19 genes shared with murine embryonic, hematopoietic, and neural stem cells. This generalized stem cell program allowed the identification of potential CSC regulators, which were related mainly to metabolic processes. Using an siRNA genetic screen designed to target the 19 genes, we validated the functional role of this stem cell program in the regulation of breast CSC biology. Our work offers a proof of the functional importance of CSCs in breast cancer, and it establishes the reliability of PDXs for use in developing personalized CSC therapies for patients with breast cancer.

  13. Breast Cancer In Women

    Science.gov (United States)

    This infographic shows the Breast Cancer Subtypes in Women. It’s important for guiding treatment and predicting survival. Know the Science: HR = Hormone receptor. HR+ means tumor cells have receptors for the hormones estrogen or progesterone, which can promote the growth of HR+ tumors. Hormone therapies like tamoxifen can be used to treat HR+ tumors. HER2 = Human epidermal growth Factor receptor, HER2+ means tumor cells overexpress (make high levels of) a protein, called HE2/neu, which has been shown to be associated with certain aggressive types of breast cancer. Trastuzumab and some other therapies can target cells that overexpress HER2. HR+/HER2, aka “LuminalA”. 73% of all breast cancer cases: best prognosis, most common subtype for every race, age, and poverty level. HR-/HER2, aka “Triple Negative”: 13% of all breast cancer cases, Worst prognosis, Non-Hispanic blacks have the highest rate of this subtype at every age and poverty level. HR+/HER2+, aka “Luminal B”, 10% of all breast cancer cases, little geographic variation by state. HR-/HER2+, aka”HER2-enriched”, 5% of all breast cancer cases, lowest rates for all races and ethnicities. www.cancer.gov Source: Special section of the Annual Report to the Nation on the Status of Cancer, 1975-2011.

  14. Computer aided breast density evaluation in cone beam breast CT

    Science.gov (United States)

    Zhang, Xiaohua; Ning, Ruola

    2011-03-01

    Cone Beam Breast CT is a three-dimensional breast imaging modality with high contrast resolution and no tissue overlap. With these advantages, it is possible to measure volumetric breast density accurately and quantitatively with CBBCT 3D images. Three major breast components need to be segmented: skin, fat and glandular tissue. In this research, a modified morphological processing is applied to the CBBCT images to detect and remove the skin of the breast. After the skin is removed, a 2-step fuzzy clustering scheme is applied to the CBBCT image volume to adaptively cluster the image voxels into fat and glandular tissue areas based on the intensity of each voxel. Finally, the CBBCT breast volume images are divided into three categories: skin, fat and glands. Clinical data is used and the quantitative CBBCT breast density evaluation results are compared with the mammogram-based BIRADS breast density categories.

  15. Breast self examination and breast cancer: Knowledge and practice ...

    African Journals Online (AJOL)

    Medical students must possess the appropriate knowledge .... Table 2: Likert's scale scores on breast cancer-related knowledge levels. Variable. Preclinical. Clinical ... Routine alcohol consumption increases the risk of breast cancer. 50. 41. 9.

  16. Aluminium and the human breast.

    Science.gov (United States)

    Darbre, P D

    2016-06-01

    The human population is exposed to aluminium (Al) from diet, antacids and vaccine adjuvants, but frequent application of Al-based salts to the underarm as antiperspirant adds a high additional exposure directly to the local area of the human breast. Coincidentally the upper outer quadrant of the breast is where there is also a disproportionately high incidence of breast cysts and breast cancer. Al has been measured in human breast tissues/fluids at higher levels than in blood, and experimental evidence suggests that at physiologically relevant concentrations, Al can adversely impact on human breast epithelial cell biology. Gross cystic breast disease is the most common benign disorder of the breast and evidence is presented that Al may be a causative factor in formation of breast cysts. Evidence is also reviewed that Al can enable the development of multiple hallmarks associated with cancer in breast cells, in particular that it can cause genomic instability and inappropriate proliferation in human breast epithelial cells, and can increase migration and invasion of human breast cancer cells. In addition, Al is a metalloestrogen and oestrogen is a risk factor for breast cancer known to influence multiple hallmarks. The microenvironment is established as another determinant of breast cancer development and Al has been shown to cause adverse alterations to the breast microenvironment. If current usage patterns of Al-based antiperspirant salts contribute to causation of breast cysts and breast cancer, then reduction in exposure would offer a strategy for prevention, and regulatory review is now justified. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. Side-stream cigarette smoke accentuates immunomodulation during murine AIDS.

    Science.gov (United States)

    Zhang, Jin; Du Ester, En-Jie; Watson, Ronald Ross

    2002-05-01

    Side-stream cigarette smoke has become a hotly debated social, political, and scientific health and safety issue for nonsmokers. The harmful influences of side-stream cigarette smoke on human health are its adverse effects on the immune system, especially when already compromised by other agents. Acquired immune deficiency syndrome (AIDS) is a clinical disorder caused by human immunodeficiency virus (HIV). To facilitate studies, murine AIDS was induced in C57BL/6 mice by LP-BM5 murine leukemia virus infection, which mimics human AIDS. After 2 weeks of retroviral infection, the mice were exposed to side-stream cigarette smoke for 30 min, 5 days/week for 12 weeks using a side-stream cigarette smoke exposure system. Murine retrovirus infection reduced the in vitro proliferation of T lymphocytes stimulated by concanavalin A, increased the release of pro-inflammatory cytokine interleukin-6 (IL-6) tumor necrosis factor-alpha (TNF-alpha), increased the hepatic lipid peroxidation and decreased the alpha-tocopherol levels in liver, lung and heart. Concomitant side-stream cigarette smoke exposure for 12 weeks further inhibited the proliferation of T cells, increased the release of TNF-alpha, IL-6 cytokines and enhanced the hepatic lipid peroxidation from retrovirus infected mice. The loss of alpha-tocopherol was also further enhanced by side-stream cigarette smoke exposure during retrovirus infection. Our conclusions are that side-stream cigarette smoke induced increasing oxidative stress, reducing nutrient concentrations and suppressing immune function could make mice with murine AIDS more susceptible to opportunistic infections, potentially accelerating murine AIDS progression. Thus, the reduction of side-stream cigarette smoke exposure is an important health issue in AIDS patients to improve the quality and quantity of their lives.

  18. Preclinical Evaluation of Oncolytic Δγ134.5 Herpes Simplex Virus Expressing Interleukin-12 for Therapy of Breast Cancer Brain Metastases

    Directory of Open Access Journals (Sweden)

    James J. Cody

    2012-01-01

    Full Text Available The metastasis of breast cancer to the brain and central nervous system (CNS is a problem of increasing importance. As improving treatments continue to extend patient survival, the incidence of CNS metastases from breast cancer is on the rise. New treatments are needed, as current treatments are limited by deleterious side effects and are generally palliative. We have previously described an oncolytic herpes simplex virus (HSV, designated M002, which lacks both copies of the γ134.5 neurovirulence gene and carries a murine interleukin 12 (IL-12 expression cassette, and have validated its antitumor efficacy in a variety of preclinical models of primary brain tumors. However, M002 has not been yet evaluated for use against metastatic brain tumors. Here, we demonstrate the following: both human breast cancer and murine mammary carcinoma cells support viral replication and IL-12 expression from M002; M002 replicates in and destroys breast cancer cells from a variety of histological subtypes, including “triple-negative” and HER2 overexpressing; M002 improves survival in an immunocompetent model more effectively than does a non-cytokine control virus. Thus, we conclude from this proof-of-principle study that a γ134.5-deleted IL-12 expressing oncolytic HSV may be a potential new therapy for breast cancer brain metastases.

  19. Education and Outreach for Breast Imaging and Breast Cancer Patients

    Science.gov (United States)

    2003-07-01

    the project was the development of an educational intervention ( flip chart ) for physicians to use in the clinic setting when discussing breast...Procedure Scheduling on Breast Biopsy Patient Outcomes The first phase of this project is the development of an educational flip chart for...breast biopsy and breast cancer survivors to guide the content of the flip chart b) Develop outline and overall format c) Identify/develop

  20. Directed evolution and targeted mutagenesis to murinize Listeria monocytogenes internalin A for enhanced infectivity in the murine oral infection model.

    LENUS (Irish Health Repository)

    Monk, Ian R

    2010-01-01

    Internalin A (InlA) is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells.

  1. Comparison of the tumor growth and metastasis of tumors from three luciferase-labeled mouse breast cancer cell lines%三株荧光素酶标记的小鼠乳腺癌细胞在小鼠体内生长及转移的比较

    Institute of Scientific and Technical Information of China (English)

    李小颖; 马元武; 张连峰

    2013-01-01

    luciferase-labeled mouse breast cancer cell lines (4T1-Luc, 66cl4-Luc and 4TO7-Luc) by bioluminescence imaging system, and to develop ideal tumor models and living animal analysis technique for research of tumor metastasis and anti-metastatic therapy. Method A vector containing luciferase gene was constructed and transfected into mouse breast cancer cells and selected with G418 to obtain stable Luc-expressing clones. The cells in logarithmic phase were collected and diluted to 1 × 107 cells/ mL. Then 0. 1 mL cell suspension was inoculated into the second mammary fat pad on the right side of normal BALB/c mice to establish orthotopic tumor models. Another 0. 1 mL cell suspension was intravenously injected into the tail vein of BALB/c mice to establish metastasis models. Their tumorigenesis and metastasis were analyzed in vivo. Result Stable Luc-expressing cell lines were obtained. The whole-body optical imaging revealed that orthotopical tumors formed 7 days after cell inoculation. At 28 days after inoculation, the tumor size of 4T1 cells was the biggest, that of 66cl4 cells was the second, and that of 4TO7 cells was the smallest. At 35 days after intravenous inoculation, the tumor sizes were similar among the three cell lines, while tumor metastasis were found from the 4T1 and 66cl4 tumors. The metastasis of 4T1 tumors was more serious than that of 66cl4 tumors. 4TO7 tumors didn't cause metastasis. At 42 days after intravenous inoculation, the tumor sizes were similar among the three cell lines. The metastasis of 4T1 and 66cl4 tumors became more serious with the time passed, and the metastasis of 4T1 tumors were more extensive than that of 66cl4 tumors. 4TO7 tumors still didn't show metastasis. At 7 days after intravenous inoculation, the whole-body optical imaging showed the presence of tumor formation in the lungs. The strongest fluorescence signal was observed in 4T1 tumors, followed by 4TO7 tumors, and weakest in the 66cl4 tumors. At 14 days after intravenous

  2. In vivo fluorescence imaging reveals the promotion of mammary tumorigenesis by mesenchymal stromal cells.

    Directory of Open Access Journals (Sweden)

    Chien-Chih Ke

    Full Text Available Mesenchymal stromal cells (MSCs are multipotent adult stem cells which are recruited to the tumor microenvironment (TME and influence tumor progression through multiple mechanisms. In this study, we examined the effects of MSCs on the tunmorigenic capacity of 4T1 murine mammary cancer cells. It was found that MSC-conditioned medium increased the proliferation, migration, and efficiency of mammosphere formation of 4T1 cells in vitro. When co-injected with MSCs into the mouse mammary fat pad, 4T1 cells showed enhanced tumor growth and generated increased spontaneous lung metastasis. Using in vivo fluorescence color-coded imaging, the interaction between GFP-expressing MSCs and RFP-expressing 4T1 cells was monitored. As few as five 4T1 cells could give rise to tumor formation when co-injected with MSCs into the mouse mammary fat pad, but no tumor was formed when five or ten 4T1 cells were implanted alone. The elevation of tumorigenic potential was further supported by gene expression analysis, which showed that when 4T1 cells were in contact with MSCs, several oncogenes, cancer markers, and tumor promoters were upregulated. Moreover, in vivo longitudinal fluorescence imaging of tumorigenesis revealed that MSCs created a vascularized environment which enhances the ability of 4T1 cells to colonize and proliferate. In conclusion, this study demonstrates that the promotion of mammary cancer progression by MSCs was achieved through the generation of a cancer-enhancing microenvironment to increase tumorigenic potential. These findings also suggest the potential risk of enhancing tumor progression in clinical cell therapy using MSCs. Attention has to be paid to patients with high risk of breast cancer when considering cell therapy with MSCs.

  3. Increasing Breast Cancer Surveillance Among African American Breast Cancer Survivors

    Science.gov (United States)

    2010-01-01

    Family history of breast cancer  specifically mother or sister diagnosed with breast cancer  Not the same as genetic risk for breast cancer...treatment. Table 5 presents sociodemographic variables for the first 20 SIS participants. The majority of participants were African American, unmarried

  4. Genetics Home Reference: breast cancer

    Science.gov (United States)

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions breast cancer breast cancer Enable ...

  5. PET scan for breast cancer

    Science.gov (United States)

    ... radioactive substance (called a tracer) to look for breast cancer. This tracer can help identify areas of cancer ... only after a woman has been diagnosed with breast cancer. It is done to see if the cancer ...

  6. Causes of breast lumps (image)

    Science.gov (United States)

    ... breast lumps are benign (non-cancerous), as in fibroadenoma, a condition that mostly affects women under age ... with the menstrual cycle, whereas a lump from fibroadenoma does not. While most breast lumps are benign, ...

  7. 6 Common Cancers - Breast Cancer

    Science.gov (United States)

    ... have revolutionized breast cancer treatment: tamoxifen (Nolvadex) and trastuzumab (Herceptin). Bernard Fisher, M.D., of the University of ... breast tumors. Dr. Slamon and his colleagues developed trastuzumab (Herceptin). Trastuzumab, a monoclonal antibody, was the first ...

  8. Inflammatory breast cancer: an overview

    NARCIS (Netherlands)

    Uden, D.J. van; Laarhoven, H.W.M. van; Westenberg, A.H.; Wilt, J.H. de; Blanken-Peeters, C.F.

    2015-01-01

    Inflammatory breast cancer (IBC) is the most aggressive entity of breast cancer. Management involves coordination of multidisciplinary management and usually includes neoadjuvant chemotherapy, ablative surgery if a tumor-free resection margin is expected and locoregional radiotherapy. This multimoda

  9. Benign breast lesions in Kano

    African Journals Online (AJOL)

    Background; Non-malignant diseases of the breast have assumed increased importance ... This was followed by fibroadenoma accounting for 28.8% with a mean age of 21 ... relevance of this study. ... benign breast lesion in Kano accounting.

  10. Preparing for Breast Reconstruction Surgery

    Science.gov (United States)

    ... Cancer Breast Reconstruction Surgery Preparing for Breast Reconstruction Surgery Your surgeon can help you know what to ... The plan for follow-up Costs Understanding your surgery costs Health insurance policies often cover most or ...

  11. Aluminium in human breast tissue.

    Science.gov (United States)

    Exley, Christopher; Charles, Lisa M; Barr, Lester; Martin, Claire; Polwart, Anthony; Darbre, Philippa D

    2007-09-01

    Aluminium is omnipresent in everyday life and increased exposure is resulting in a burgeoning body burden of this non-essential metal. Personal care products are potential contributors to the body burden of aluminium and recent evidence has linked breast cancer with aluminium-based antiperspirants. We have used graphite furnace atomic absorption spectrometry (GFAAS) to measure the aluminium content in breast biopsies obtained following mastectomies. The aluminium content of breast tissue and breast tissue fat were in the range 4-437 nmol/g dry wt. and 3-192 nmol/g oil, respectively. The aluminium content of breast tissue in the outer regions (axilla and lateral) was significantly higher (P=0.033) than the inner regions (middle and medial) of the breast. Whether differences in the regional distribution of aluminium in the breast are related to the known higher incidence of tumours in the outer upper quadrant of the breast remains to be ascertained.

  12. Breast Cancer in Young Women

    Science.gov (United States)

    ... NPCR 2017 CDC National Cancer Conference Stay Informed Breast Cancer in Young Women Recommend on Facebook Tweet Share Compartir Syndicate this page Marleah's family history of breast cancer was her motivation for pursuing a career where ...

  13. Preventing Breast Cancer: Making Progress

    Science.gov (United States)

    ... Navigation Bar Home Current Issue Past Issues Preventing Breast Cancer: Making Progress Past Issues / Fall 2006 Table of ... 000 women will have been diagnosed with invasive breast cancer, and nearly 41,000 women will die from ...

  14. Early detection of breast cancer.

    Science.gov (United States)

    Nettles-Carlson, B

    1989-01-01

    Timely, comprehensive screening for breast cancer is a major, though often overlooked, component of primary health care for women. This article reviews the scientific rationale for screening and outlines the current recommendations of the American Cancer Society and the U.S. Preventive Services Task Force regarding the use of mammography, clinical breast examination (CBE), and breast self-examination (BSE). Nursing interventions to decrease barriers to effective screening are discussed, and an expanded role of nurses in breast cancer screening is proposed.

  15. Breast cancer in young women

    OpenAIRE

    Barnadas, Agustí; Vázquez, Carlos

    2010-01-01

    International audience; Breast surgery in young women is associated with a significant impact on the patient's health-related quality of life due to changes in body image and sexuality. These perceptions are being increasingly considered as integral to understanding health outcomes. Of the available surgical techniques, mastectomy is associated with the highest psychosocial morbidity, and breast-conserving surgery with the least. If breast-conserving surgery is not an option, breast reconstru...

  16. Breast cancer in young women

    OpenAIRE

    2010-01-01

    Abstract Breast surgery in young women is associated with a significant impact on the patient?s health-related quality of life due to changes in body image and sexuality. These perceptions are being increasingly considered as integral to understanding health outcomes. Of the available surgical techniques, mastectomy is associated with the highest psychosocial morbidity, and breast-conserving surgery with the least. If breast-conserving surgery is not an option, breast reconstructio...

  17. The Premenopausal Breast Cancer Collaboration

    DEFF Research Database (Denmark)

    Nichols, Hazel B; Schoemaker, Minouk J; Wright, Lauren B

    2017-01-01

    Breast cancer is a leading cancer diagnosis among premenopausal women around the world. Unlike rates in postmenopausal women, incidence rates of advanced breast cancer have increased in recent decades for premenopausal women. Progress in identifying contributors to breast cancer risk among premen...

  18. Dysregulated expression of Fau and MELK is associated with poor prognosis in breast cancer.

    Science.gov (United States)

    Pickard, Mark R; Green, Andrew R; Ellis, Ian O; Caldas, Carlos; Hedge, Vanessa L; Mourtada-Maarabouni, Mirna; Williams, Gwyn T

    2009-01-01

    Programmed cell death through apoptosis plays an essential role in the hormone-regulated physiological turnover of mammary tissue. Failure of this active gene-dependent process is central both to the development of breast cancer and to the appearance of the therapy-resistant cancer cells that produce clinical relapse. Functional expression cloning in two independent laboratories has identified Finkel-Biskis-Reilly murine sarcoma virus-associated ubiquitously expressed gene (Fau) as a novel apoptosis regulator and candidate tumour suppressor. Fau modifies apoptosis-controller Bcl-G, which is also a key target for candidate oncoprotein maternal embryonic leucine zipper kinase (MELK). We have used RNA interference to downregulate Fau and Bcl-G expression, both simultaneously and independently, in breast cancer cells in vitro to determine the importance of their roles in apoptosis. Expression of Fau, Bcl-G and MELK was measured by quantitative RT-PCR in breast cancer tissue and in matched breast epithelial tissue from the same patients. Expression data of these genes obtained using microarrays from a separate group of patients were related to patient survival in Kaplan-Meier analyses. siRNA-mediated downregulation of either Fau or Bcl-G expression inhibited apoptosis, and the inhibition produced by combining the two siRNAs was consistent with control of Bcl-G by Fau. Fau expression is significantly reduced in breast cancer tissue and this reduction is associated with poor patient survival, as predicted for a candidate breast cancer tumour suppressor. In addition, MELK expression is increased in breast cancer tissue and this increase is also associated with poor patient survival, as predicted for a candidate oncogene. Bcl-G expression is reduced in breast cancer tissue but decreased Bcl-G expression showed no correlation with survival, indicating that the most important factors controlling Bcl-G activity are post-translational modification (by Fau and MELK) rather than

  19. Accessory breast tissue in axilla masquerading as breast cancer recurrence

    Directory of Open Access Journals (Sweden)

    Goyal Shikha

    2008-01-01

    Full Text Available Ectopic or accessory breast tissue is most commonly located in the axilla, though it may be present anywhere along the milk line. Development is hormone dependent, similar to normal breast tissue. These lesions do not warrant any intervention unless they produce discomfort, thus their identification and distinction from other breast pathologies, both benign and malignant, is essential. We report a case with locally advanced breast cancer who presented with an ipsilateral axillary mass following surgery, radiotherapy, and chemotherapy. Subsequent evaluation with excision biopsy showed duct ectasia in axillary breast tissue and the patient was continued on hormone therapy with tamoxifen.

  20. Biodegradable polymeric micelles coencapsulating paclitaxel and honokiol: a strategy for breast cancer therapy in vitro and in vivo

    Science.gov (United States)

    Wang, Ning; Wang, Zhihan; Nie, Shihong; Song, Linjiang; He, Tao; Yang, Suleixin; Yang, Xi; Yi, Cheng; Wu, Qinjie; Gong, Changyang

    2017-01-01

    The combination of chemotherapy drugs attracts more attention in clinical cancer trials. However, the poor water solubility of chemotherapeutic drugs restricts their anticancer application. In order to improve antitumor efficiency and reduce side effects of free drugs, we prepared paclitaxel (PTX) and honokiol (HK) combination methoxy poly(ethylene glycol)–poly(caprolactone) micelles (P–H/M) by solid dispersion method against breast cancer. The particle size of P–H/M was 28.7±2.5 nm, and transmission electron microscope image confirmed that P–H/M were spherical in shape with small particle size. After being encapsulated in micelles, the release of PTX or HK showed a sustained behavior in vitro. In addition, both the cytotoxicity and the cellular uptake of P–H/M were increased in 4T1 cells, and P–H/M induced more apoptosis than PTX-loaded micelles or HK-loaded micelles, as analyzed by flow cytometry assay and Western blot. Furthermore, the antitumor effect of P–H/M was significantly improved compared with PTX-loaded micelles or HK-loaded micelles in vivo. P–H/M were more effective in inhibiting tumor proliferation, inducing tumor apoptosis, and decreasing the density of microvasculature. Moreover, bioimaging analysis showed that drug-loaded polymeric micelles could accumulate more in tumor tissues compared with the free drug. Our results suggested that P–H/M may have potential applications in breast cancer therapy. PMID:28260895

  1. The application of surgical navigation system using optical molecular imaging technology in orthotopic breast cancer and metastasis studies

    Science.gov (United States)

    Chi, Chongwei; Zhang, Qian; Kou, Deqiang; Ye, Jinzuo; Mao, Yamin; Qiu, Jingdan; Wang, Jiandong; Yang, Xin; Du, Yang; Tian, Jie

    2014-02-01

    Currently, it has been an international focus on intraoperative precise positioning and accurate resection of tumor and metastases. The methods such as X-rays, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) have played an important role in preoperative accurate diagnosis. However, most of them are inapplicable for intraoperative surgery. We have proposed a surgical navigation system based on optical molecular imaging technology for intraoperative detection of tumors and metastasis. This system collects images from two CCD cameras for real-time fluorescent and color imaging. For image processing, the template matching algorithm is used for multispectral image fusion. For the application of tumor detection, the mouse breast cancer cell line 4T1-luc, which shows highly metastasis, was used for tumor model establishment and a model of matrix metalloproteinase (MMP) expressing breast cancer. The tumor-bearing nude mice were given tail vein injection of MMP 750FAST (PerkinElmer, Inc. USA) probe and imaged with both bioluminescence and fluorescence to assess in vivo binding of the probe to the tumor and metastases sites. Hematoxylin and eosin (H&E) staining was performed to confirm the presence of tumor and metastasis. As a result, one tumor can be observed visually in vivo. However liver metastasis has been detected under surgical navigation system and all were confirmed by histology. This approach helps surgeons to find orthotopic tumors and metastasis during intraoperative resection and visualize tumor borders for precise positioning. Further investigation is needed for future application in clinics.

  2. Ultrasound characterization of breast masses

    Science.gov (United States)

    Gokhale, Sudheer

    2009-01-01

    A lump in the breast is a cause of great concern. High frequency, high-resolution USG helps in its evaluation. This is exemplified in women with dense breast tissue where USG is useful in detecting small breast cancers that are not seen on mammography. Several studies in the past have addressed the issue of differentiating benign from malignant lesions in the breast. The American College of Radiology has also brought out a BIRADS-US classification system for categorizing focal breast lesions. PMID:19881096

  3. Lactobacillus rhamnosus GG as an Effective Probiotic for Murine Giardiasis

    Directory of Open Access Journals (Sweden)

    Nisha Goyal

    2011-01-01

    Full Text Available The gut microflora is an important constituent in the intestinal mucosal barrier and has been introduced as the concept of probiotic therapy that beneficially affects the host by improving its intestinal microbial balance. Therefore, the main objective of the study was to explore the protective potential of various lactobacilli strains for murine giardiasis. By experimentation, it was found that the probiotic supplementation of either Lactobacillus casei, L. acidophilus, L. plantarum, or L. rhamnosus GG, 7 days prior to inoculation with G. lamblia trophozoites, reduced the rate of cyst excretion compared with Giardia-infected mice. Interestingly, L. GG was found to be the most effective probiotic in reducing the duration of giardia cycle and acts as an effective prophylactic probiotic for murine giardiasis but needs to be clinically correlated due to entirely different human microflora.

  4. Effects of the murine skull in optoacoustic brain microscopy.

    Science.gov (United States)

    Kneipp, Moritz; Turner, Jake; Estrada, Héctor; Rebling, Johannes; Shoham, Shy; Razansky, Daniel

    2016-01-01

    Despite the great promise behind the recent introduction of optoacoustic technology into the arsenal of small-animal neuroimaging methods, a variety of acoustic and light-related effects introduced by adult murine skull severely compromise the performance of optoacoustics in transcranial imaging. As a result, high-resolution noninvasive optoacoustic microscopy studies are still limited to a thin layer of pial microvasculature, which can be effectively resolved by tight focusing of the excitation light. We examined a range of distortions introduced by an adult murine skull in transcranial optoacoustic imaging under both acoustically- and optically-determined resolution scenarios. It is shown that strong low-pass filtering characteristics of the skull may significantly deteriorate the achievable spatial resolution in deep brain imaging where no light focusing is possible. While only brain vasculature with a diameter larger than 60 µm was effectively resolved via transcranial measurements with acoustic resolution, significant improvements are seen through cranial windows and thinned skull experiments.

  5. T Cell Integrin Overexpression as a Model of Murine Autoimmunity

    Directory of Open Access Journals (Sweden)

    Yung Raymond L.

    2003-01-01

    Full Text Available Integrin adhesion molecules have important adhesion and signaling functions. They also play a central role in the pathogenesis of many autoimmune diseases. Over the past few years we have described a T cell adoptive transfer model to investigate the role of T cell integrin adhesion molecules in the development of autoimmunity. This report summarizes the methods we used in establishing this murine model. By treating murine CD4+ T cells with DNA hypomethylating agents and by transfection we were able to test the in vitro effects of integrin overexpression on T cell autoreactive proliferation, cytotoxicity, adhesion and trafficking. Furthermore, we showed that the ability to induce in vivo autoimmunity may be unique to the integrin lymphocyte function associated antigen-1 (LFA-1.

  6. Mindfulness Meditation or Survivorship Education in Improving Behavioral Symptoms in Younger Stage 0-III Breast Cancer Survivors (Pathways to Wellness)

    Science.gov (United States)

    2017-03-21

    Cancer Survivor; Early-Stage Breast Carcinoma; Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  7. Schisandrin B attenuates cancer invasion and metastasis via inhibiting epithelial-mesenchymal transition.

    Directory of Open Access Journals (Sweden)

    Zhen Liu

    Full Text Available BACKGROUND: Metastasis is the major cause of cancer related death and targeting the process of metastasis has been proposed as a strategy to combat cancer. Therefore, to develop candidate drugs that target the process of metastasis is very important. In the preliminary studies, we found that schisandrin B (Sch B, a naturally-occurring dibenzocyclooctadiene lignan with very low toxicity, could suppress cancer metastasis. METHODOLOGY: BALB/c mice were inoculated subcutaneously or injected via tail vein with murine breast cancer 4T1 cells. Mice were divided into Sch B-treated and control groups. The primary tumor growth, local invasion, lung and bone metastasis, and survival time were monitored. Tumor biopsies were examined immuno- and histo-pathologically. The inhibitory activity of Sch B on TGF-β induced epithelial-mesenchymal transition (EMT of 4T1 and primary human breast cancer cells was assayed. PRINCIPAL FINDINGS: Sch B significantly suppressed the spontaneous lung and bone metastasis of 4T1 cells inoculated s.c. without significant effect on primary tumor growth and significantly extended the survival time of these mice. Sch B did not inhibit lung metastasis of 4T1 cells that were injected via tail vein. Delayed start of treatment with Sch B in mice with pre-existing tumors did not reduce lung metastasis. These results suggested that Sch B acted at the step of local invasion. Histopathological evidences demonstrated that the primary tumors in Sch B group were significantly less locally invasive than control tumors. In vitro assays demonstrated that Sch B could inhibit TGF-β induced EMT of 4T1 cells and of primary human breast cancer cells. CONCLUSIONS: Sch B significantly suppresses the lung and bone metastasis of 4T1 cells via inhibiting EMT, suggesting its potential application in targeting the process of cancer metastasis.

  8. Antibody responses against xenotropic murine leukemia virus-related virus envelope in a murine model.

    Directory of Open Access Journals (Sweden)

    Natalia Makarova

    Full Text Available BACKGROUND: Xenotropic murine leukemia virus-related virus (XMRV was recently discovered to be the first human gammaretrovirus that is associated with chronic fatigue syndrome and prostate cancer (PC. Although a mechanism for XMRV carcinogenesis is yet to be established, this virus belongs to the family of gammaretroviruses well known for their ability to induce cancer in the infected hosts. Since its original identification XMRV has been detected in several independent investigations; however, at this time significant controversy remains regarding reports of XMRV detection/prevalence in other cohorts and cell type/tissue distribution. The potential risk of human infection, coupled with the lack of knowledge about the basic biology of XMRV, warrants further research, including investigation of adaptive immune responses. To study immunogenicity in vivo, we vaccinated mice with a combination of recombinant vectors expressing codon-optimized sequences of XMRV gag and env genes and virus-like particles (VLP that had the size and morphology of live infectious XMRV. RESULTS: Immunization elicited Env-specific binding and neutralizing antibodies (NAb against XMRV in mice. The peak titers for ELISA-binding antibodies and NAb were 1:1024 and 1:464, respectively; however, high ELISA-binding and NAb titers were not sustained and persisted for less than three weeks after immunizations. CONCLUSIONS: Vaccine-induced XMRV Env antibody titers were transiently high, but their duration was short. The relatively rapid diminution in antibody levels may in part explain the differing prevalences reported for XMRV in various prostate cancer and chronic fatigue syndrome cohorts. The low level of immunogenicity observed in the present study may be characteristic of a natural XMRV infection in humans.

  9. Osteopontin Is Upregulated in Human and Murine Acute Schistosomiasis Mansoni

    Science.gov (United States)

    Pereira, Thiago Almeida; Syn, Wing-Kin; Amâncio, Frederico Figueiredo; Cunha, Pedro Henrique Diniz; Caporali, Julia Fonseca Morais; Trindade, Guilherme Vaz de Melo; Santos, Elisângela Trindade; Souza, Márcia Maria; Andrade, Zilton Araújo; Witek, Rafal P; Secor, William Evan; Pereira, Fausto Edmundo Lima; Lambertucci, José Roberto; Diehl, Anna Mae

    2016-01-01

    Background Symptomatic acute schistosomiasis mansoni is a systemic hypersensitivity reaction against the migrating schistosomula and mature eggs after a primary infection. The mechanisms involved in the pathogenesis of acute schistosomiasis are not fully elucidated. Osteopontin has been implicated in granulomatous reactions and in acute hepatic injury. Our aims were to evaluate if osteopontin plays a role in acute Schistosoma mansoni infection in both human and experimentally infected mice and if circulating OPN levels could be a novel biomarker of this infection. Methodology/Principal Findings Serum/plasma osteopontin levels were measured by ELISA in patients with acute (n = 28), hepatointestinal (n = 26), hepatosplenic (n = 39) schistosomiasis and in uninfected controls (n = 21). Liver osteopontin was assessed by immunohistochemistry in needle biopsies of 5 patients. Sera and hepatic osteopontin were quantified in the murine model of schistosomiasis mansoni during acute (7 and 8 weeks post infection, n = 10) and chronic (30 weeks post infection, n = 8) phase. Circulating osteopontin levels are increased in patients with acute schistosomiasis (p = 0.0001). The highest levels of OPN were observed during the peak of clinical symptoms (7–11 weeks post infection), returning to baseline level once the granulomas were modulated (>12 weeks post infection). The plasma levels in acute schistosomiasis were even higher than in hepatosplenic patients. The murine model mirrored the human disease. Macrophages were the major source of OPN in human and murine acute schistosomiasis, while the ductular reaction maintains OPN production in hepatosplenic disease. Soluble egg antigens from S. mansoni induced OPN expression in primary human kupffer cells. Conclusions/Significance S. mansoni egg antigens induce the production of OPN by macrophages in the necrotic-exudative granulomas characteristic of acute schistosomiasis mansoni. Circulating OPN levels are upregulated in human and

  10. Breast cancer epidemiology.

    Science.gov (United States)

    Kelsey, J L; Berkowitz, G S

    1988-10-15

    The various risk factors for breast cancer have been recognized for many years. A table lists these established breast cancer risk factors together with the approximate magnitude of the increase in risk associated with them. Breast cancer incidence rates increase with age throughout the life span in Western countries, although the rate of increase is greater up to age 50 years than after 50 years. Breast cancer is more common among women in upper rather than lower social classes, among women who never have been married, among women living in urban areas, among women living in the northern US than in the southern US, and among whites than blacks, at least among those over age 50. Women in North American and Northern European countries have the highest risk for breast cancer, women in Southern European and Latin American countries are at intermediate risk, and women in Africa and Asian countries have the lowest risk. Yet, rapid rates of increase in incident rates have been noted in recent years in many Asian, Central European, and some South American countries. The later the age at which a woman has her 1st full-term pregnancy, the higher her risk for breast cancer; the earlier the age at menarche and the later the age at menopause the higher the risk; and among women who have a premenopausal oophorectomy, the earlier the age at which this occurs the lower the risk. Among postmenopausal women, obesity is associated with an increase in risk. Lactation is negatively associated with subsequent breast cancer risk. Some current research is considering potential risk factors that have not been well studied in the past, including alcohol consumption, cigarette smoking, caffeine consumption, exposure to diethylstilbestrol (DES), emotional stress, exposure to electric power, and lack of physical activity. Other areas of current research reviewed here include radiation, mammographic parenchymal patterns, a high-fat diet, use of oral contraceptives (OCs), use of estrogen

  11. Hamartoma Breast, Chondromatous Type

    Directory of Open Access Journals (Sweden)

    Vidya Bhat

    2011-07-01

    Full Text Available This case report describes an exceedingly rare case of hamartoma of breast with predominantly chondroid stroma. A 45 year old lady presented with a mobile lump in the upper outer quadrant of left breast, clinically diagnosed as fibroadenoma. Mammography and FNAC were not done. She underwent lumpectomy and we received the specimen measuring 7x5x3cm. Cut surface of which revealed grey white nodule with glistening surface. Histopathologically we found a circumscribed lesion with predominantly mature hyaline cartilage separated by fibrocollagenous bands.

  12. [Occult multicentric breast cancer].

    Science.gov (United States)

    Vtorushin, S V; Zab'ialova, M V; Glushchenko, S A; Perel'muter, V M; Slonimskaia, E M

    2009-01-01

    The study included 92 patients with invasive ductal breast cancer (T2-4N0-2M0-1). In 38 cases, tumor growth was unicentric while histologically identifiable ones as multicentric in 44. Multicentricity mostly occurred in cases of macroscopically-identifiable nodes located in the central segments of the breast. Clinically-identifiable nodes of multicentric tumor growth measured more than 3 cm. Multicentric tumors were mostly grade III, featured lower expression of sex hormone receptors and positive Her2 status.

  13. Delayed breast reconstruction with implants after invasive breast cancer does not impair prognosis

    DEFF Research Database (Denmark)

    Hölmich, Lisbet Rosenkrantz; Düring, Maria; Henriksen, Trine Foged;

    2008-01-01

    We investigated if delayed breast implant reconstruction after breast cancer impairs prognosis. Using data from the Danish Breast Cancer Cooperative Group register, we identified all women......We investigated if delayed breast implant reconstruction after breast cancer impairs prognosis. Using data from the Danish Breast Cancer Cooperative Group register, we identified all women...

  14. Diagnostic imaging advances in murine models of colitis.

    Science.gov (United States)

    Brückner, Markus; Lenz, Philipp; Mücke, Marcus M; Gohar, Faekah; Willeke, Peter; Domagk, Dirk; Bettenworth, Dominik

    2016-01-21

    Inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis are chronic-remittent inflammatory disorders of the gastrointestinal tract still evoking challenging clinical diagnostic and therapeutic situations. Murine models of experimental colitis are a vital component of research into human IBD concerning questions of its complex pathogenesis or the evaluation of potential new drugs. To monitor the course of colitis, to the present day, classical parameters like histological tissue alterations or analysis of mucosal cytokine/chemokine expression often require euthanasia of animals. Recent advances mean revolutionary non-invasive imaging techniques for in vivo murine colitis diagnostics are increasingly available. These novel and emerging imaging techniques not only allow direct visualization of intestinal inflammation, but also enable molecular imaging and targeting of specific alterations of the inflamed murine mucosa. For the first time, in vivo imaging techniques allow for longitudinal examinations and evaluation of intra-individual therapeutic response. This review discusses the latest developments in the different fields of ultrasound, molecularly targeted contrast agent ultrasound, fluorescence endoscopy, confocal laser endomicroscopy as well as tomographic imaging with magnetic resonance imaging, computed tomography and fluorescence-mediated tomography, discussing their individual limitations and potential future diagnostic applications in the management of human patients with IBD.

  15. Evaluation of a murine single-blood-injection SAH model.

    Directory of Open Access Journals (Sweden)

    Marcel A Kamp

    Full Text Available The molecular pathways underlying the pathogenesis after subarachnoid haemorrhage (SAH are poorly understood and continue to be a matter of debate. A valid murine SAH injection model is not yet available but would be the prerequisite for further transgenic studies assessing the mechanisms following SAH. Using the murine single injection model, we examined the effects of SAH on regional cerebral blood flow (rCBF in the somatosensory (S1 and cerebellar cortex, neuro-behavioural and morphological integrity and changes in quantitative electrocorticographic and electrocardiographic parameters. Micro CT imaging verified successful blood delivery into the cisterna magna. An acute impairment of rCBF was observed immediately after injection in the SAH and after 6, 12 and 24 hours in the S1 and 6 and 12 hours after SAH in the cerebellum. Injection of blood into the foramen magnum reduced telemetric recorded total ECoG power by an average of 65%. Spectral analysis of ECoGs revealed significantly increased absolute delta power, i.e., slowing, cortical depolarisations and changes in ripples and fast ripple oscillations 12 hours and 24 hours after SAH. Therefore, murine single-blood-injection SAH model is suitable for pathophysiological and further molecular analysis following SAH.

  16. Integrin Based Isolation Enables Purification of Murine Lineage Committed Cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Laura Tarnawski

    Full Text Available In contrast to mature cardiomyocytes which have limited regenerative capacity, pluripotent stem cells represent a promising source for the generation of new cardiomyocytes. The tendency of pluripotent stem cells to form teratomas and the heterogeneity from various differentiation stages and cardiomyocyte cell sub-types, however, are major obstacles to overcome before this type of therapy could be applied in a clinical setting. Thus, the identification of extracellular markers for specific cardiomyocyte progenitors and mature subpopulations is of particular importance. The delineation of cardiomyocyte surface marker patterns not only serves as a means to derive homogeneous cell populations by FACS, but is also an essential tool to understand cardiac development. By using single-cell expression profiling in early mouse embryonic hearts, we found that a combination of integrin alpha-1, alpha-5, alpha-6 and N-cadherin enables isolation of lineage committed murine cardiomyocytes. Additionally, we were able to separate trabecular cardiomyocytes from solid ventricular myocardium and atrial murine cells. These cells exhibit expected subtype specific phenotype confirmed by electrophysiological analysis. We show that integrin expression can be used for the isolation of living, functional and lineage-specific murine cardiomyocytes.

  17. Affluence and Breast Cancer.

    Science.gov (United States)

    Lehrer, Steven; Green, Sheryl; Rosenzweig, Kenneth E

    2016-09-01

    High income, high socioeconomic status, and affluence increase breast cancer incidence. Socioeconomic status in USA breast cancer studies has been assessed by block-group socioeconomic measures. A block group is a portion of a census tract with boundaries that segregate, as far as possible, socioeconomic groups. In this study, we used US Census income data instead of block groups to gauge socioeconomic status of breast cancer patients in relationship with incidence, prognostic markers, and survival. US state breast cancer incidence and mortality data are from the U.S. Cancer Statistics Working Group, United States Cancer Statistics: 1999-2011. Three-Year-Average Median Household Income by State, 2010 to 2012, is from the U.S. Census Bureau, Current Population Survey, 2011 to 2013 Annual Social and Economic Supplements. County incomes are from the 2005-2009 American Community Survey of the U.S. Census Bureau. The American Community Survey is an ongoing statistical survey that samples a small percentage of the population yearly. Its purpose is to provide communities the information they need to plan investments and services. Breast cancer county incidence and survival data are from the National Cancer Institute's Surveillance, Epidemiology and End Results Program (SEER) data base. We analyzed SEER data from 198 counties in California, Connecticut, Georgia, Hawaii, Iowa, New Mexico, Utah, and Washington. SEER uses the Collaborative Stage (CS) Data Collection System. We have retained the SEER CS variables. There was a significant relationship of income with breast cancer incidence in 50 USA states and the District of Columbia in White women (r = 0.623, p breast cancer. Income was not correlated with 5-year survival of Black race (p = 0.364) or other races (p = 0.624). The multivariate general linear model with income as covariate, 5-year survival by race as a dependent variable, showed a significant effect of income and White race on 5-year survival (p breast cancer

  18. Intradermal Infection Model for Pathogenesis and Vaccine Studies of Murine Visceral Leishmaniasis

    OpenAIRE

    2003-01-01

    The levels of protection found in vaccine studies of murine visceral leishmaniasis are significantly lower than for cutaneous leishmaniasis; whether this is due to the high-challenge murine model employed and/or is a consequence of differences required in tissue-specific local immune responses is not understood. Consequently, an intradermal murine model of visceral leishmaniasis has been explored. Intradermal inoculation established a chronic infection in susceptible mice which was associated...

  19. Anti-inflammatory activities of mogrosides from Momordica grosvenori in murine macrophages and a murine ear edema model.

    Science.gov (United States)

    Di, Rong; Huang, Mou-Tuan; Ho, Chi-Tang

    2011-07-13

    Momordica grosvenori (Luo Han Guo), grown primarily in Guangxi province in China, has been traditionally used for thousands of years by the Chinese to make hot drinks for the treatment of sore throat and the removal of phlegm. The natural noncaloric sweetening triterpenoid glycosides (mogrosides) contained in the M. grosvenori fruits are also antioxidative, anticarcinogenic, and helpful in preventing diabetic complications. The aim of this study was to assess the anti-inflammatory properties of mogrosides in both murine macrophage RAW 264.7 cells and a murine ear edema model. The results indicate that mogrosides can inhibit inflammation induced by lipopolysaccharides (LPS) in RAW 264.7 cells by down-regulating the expression of key inflammatory genes iNOS, COX-2, and IL-6 and up-regulating some inflammation protective genes such as PARP1, BCL2l1, TRP53, and MAPK9. Similarly, in the murine ear edema model, 12-O-tetradecanoylphorbol-13-acetate-induced inflammation was inhibited by mogrosides by down-regulating COX-2 and IL-6 and up-regulating PARP1, BCL2l1, TRP53, MAPK9, and PPARδ gene expression. This study shows that the anticancer and antidiabetic effects of M. grosvenori may result in part from its anti-inflammatory activity.

  20. Hereditary breast cancer

    DEFF Research Database (Denmark)

    Larsen, Martin J; Thomassen, Mads; Gerdes, Anne-Marie

    2014-01-01

    Pathogenic mutations in BRCA1 or BRCA2 are only detected in 25% of families with a strong history of breast cancer, though hereditary factors are expected to be involved in the remaining families with no recognized mutation. Molecular characterization is expected to provide new insight into the t......Pathogenic mutations in BRCA1 or BRCA2 are only detected in 25% of families with a strong history of breast cancer, though hereditary factors are expected to be involved in the remaining families with no recognized mutation. Molecular characterization is expected to provide new insight...... into the tumor biology to guide the search of new high-risk alleles and provide better classification of the growing number of BRCA1/2 variants of unknown significance (VUS). In this review, we provide an overview of hereditary breast cancer, its genetic background, and clinical implications, before focusing...... on the pathologically and molecular features associated with the disease. Recent transcriptome and genome profiling studies of tumor series from BRCA1/2 mutation carriers as well as familial non-BRCA1/2 will be discussed. Special attention is paid to its association with molecular breast cancer subtypes as well...

  1. Breast Cancer - Early Diagnosis

    Centers for Disease Control (CDC) Podcasts

    2011-04-28

    This podcast answers a listener's question about how to tell if she has breast cancer.  Created: 4/28/2011 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 4/28/2011.

  2. Sarcoidosis of the breast.

    OpenAIRE

    Banik, S.; Bishop, P W; Ormerod, L P; O'Brien, T.E.

    1986-01-01

    Sarcoid granulomata were found incidentally in the mammary lobules adjacent to an excised fibroadenoma in a case of sarcoidosis of the breast. The diagnosis of sarcoidosis was established by the radiological finding of bilateral hilar lymphadenopathy, raised concentrations of serum angiotensin converting enzyme and lysozyme, and, finally, by a positive Kveim test.

  3. Breast Cancer Research Program

    Science.gov (United States)

    2010-09-01

    tion of tumor cells with red indicating the highest density of tumor cells at the primary tumor (4th mammary fat pad ) and purple/blue showing the...Idea Award Elaine Hardman and Philippe Georgel “ Maternal Consumption of Omega 3 Fatty Acids to Reduce Breast Cancer Risk in Offspring” FY09

  4. [Breast carcinoma in men].

    Science.gov (United States)

    Zigić, B; Balvanović, D; Rac, S; Bilbija, S

    1989-01-01

    The authors describe 8 cases of carcinoma of the male breast treated at the Clinic of Surgery, Clinical Medical Center Banja Luka in the period 1968-1988. In their discussion, the authors review contemporary findings concerning the genesis, evolution and treatment of this carcinoma.

  5. Breast reconstruction - natural tissue

    Science.gov (United States)

    ... another method called the free flap procedure, skin, fat, and muscle tissue are removed from your lower belly. This tissue ... breast that was removed. The surgeon loosens skin, fat, and muscle from this area. This tissue is then tunneled under your skin to the ...

  6. Anti-transforming growth factor ß antibody treatment rescues bone loss and prevents breast cancer metastasis to bone.

    Science.gov (United States)

    Biswas, Swati; Nyman, Jeffry S; Alvarez, JoAnn; Chakrabarti, Anwesa; Ayres, Austin; Sterling, Julie; Edwards, James; Rana, Tapasi; Johnson, Rachelle; Perrien, Daniel S; Lonning, Scott; Shyr, Yu; Matrisian, Lynn M; Mundy, Gregory R

    2011-01-01

    Breast cancer often metastasizes to bone causing osteolytic bone resorption which releases active TGFβ. Because TGFβ favors progression of breast cancer metastasis to bone, we hypothesized that treatment using anti-TGFβ antibody may reduce tumor burden and rescue tumor-associated bone loss in metastatic breast cancer. In this study we have tested the efficacy of an anti-TGFβ antibody 1D11 preventing breast cancer bone metastasis. We have used two preclinical breast cancer bone metastasis models, in which either human breast cancer cells or murine mammary tumor cells were injected in host mice via left cardiac ventricle. Using several in vivo, in vitro and ex vivo assays, we have demonstrated that anti-TGFβ antibody treatment have significantly reduced tumor burden in the bone along with a statistically significant threefold reduction in osteolytic lesion number and tenfold reduction in osteolytic lesion area. A decrease in osteoclast numbers (p = 0.027) in vivo and osteoclastogenesis ex vivo were also observed. Most importantly, in tumor-bearing mice, anti-TGFβ treatment resulted in a twofold increase in bone volume (ptreatment with anti-TGFβ antibody increased the mineral-to-collagen ratio in vivo, a reflection of improved tissue level properties. Moreover, anti-TGFβ antibody directly increased mineralized matrix formation in calverial osteoblast (p = 0.005), suggesting a direct beneficial role of anti-TGFβ antibody treatment on osteoblasts. Data presented here demonstrate that anti-TGFβ treatment may offer a novel therapeutic option for tumor-induced bone disease and has the dual potential for simultaneously decreasing tumor burden and rescue bone loss in breast cancer to bone metastases. This approach of intervention has the potential to reduce skeletal related events (SREs) in breast cancer survivors.

  7. Mucin1 antibody-conjugated dye-doped mesoporous silica nanoparticles for breast cancer detection in vivo

    Science.gov (United States)

    Vivero-Escoto, Juan L.; Moore Jeffords, Laura; Dréau, Didier; Alvarez-Berrios, Merlis; Mukherjee, Pinku

    2017-02-01

    The development of novel methods for tumor detection is a burgeoning area of research. In particular, the use of silica nanoparticles for optical imaging in the near infrared (NIR) represents a valuable tool because their chemical inertness, biocompatibility, and transparency in the ultraviolet-visible and NIR regions of the electromagnetic spectrum. Moreover, silica nanoparticles can be modified with a wide variety of functional groups such as aptamers, small molecules, antibodies and polymers. Here, we report the development of a mucin 1(MUC1)-specific dye-doped NIR emitting mesoporous silica nanoparticles (MUC1-NIR-MSN) platform for the optical detection of breast cancer tissue overexpressing human tumor-associated MUC1. We have characterized the structural properties and the in vitro performance of this system. The MSN-based optical imaging probe is non-cytotoxic and targets efficiently murine mammary epithelial cancer cells overexpressing human MUC1. Finally, the ability of MUC1-NIR-MSN contrast imaging agent to selectively detect breast cancer tumors overexpressing human tumor-associated MUC1 was successfully demonstrated in a transgenic murine mouse model. The NIR imaging experiments on tumor-bearing animals showed specific accumulation of the MSN-based probe in human MUC1-positive tumors and small signal in control tumors. We envision that this MUC1-specific MSN-based optical probe has the potential to greatly aid in screening prospective patients for early breast cancer detection and in monitoring the efficacy of drug therapy.

  8. Three-dimensional cultures modeling premalignant progression of human breast epithelial cells: role of cysteine cathepsins

    Science.gov (United States)

    Mullins, Stefanie R.; Sameni, Mansoureh; Blum, Galia; Bogyo, Matthew; Sloane, Bonnie F.; Moin, Kamiar

    2013-01-01

    The expression of the cysteine protease cathepsin B is increased in early stages of human breast cancer. To assess the potential role of cathepsin B in premalignant progression of breast epithelial cells, we employed a 3D reconstituted basement membrane overlay culture model of MCF10A human breast epithelial cells and isogenic variants that replicate the in vivo phenotypes of hyperplasia (MCF10AneoT) and atypical hyperplasia (MCF10AT1). MCF10A cells developed into polarized acinar structures with central lumens. In contrast, MCF10AneoT and MCF10AT1 cells form larger structures in which the lumens are filled with cells. CA074Me, a cell-permeable inhibitor selective for the cysteine cathepsins B and L, reduced proliferation and increased apoptosis of MCF10A, MCF10AneoT and MCF10AT1 cells in 3D culture. We detected active cysteine cathepsins in the isogenic MCF10 variants in 3D culture with GB111, a cell-permeable activity-based probe, and established differential inhibition of cathepsin B in our 3D cultures. We conclude that cathepsin B promotes proliferation and premalignant progression of breast epithelial cells. These findings are consistent with studies by others showing that deletion of cathepsin B in the transgenic MMTV-PyMT mice, a murine model that is predisposed to development of mammary cancer, reduces malignant progression. PMID:23667900

  9. Progestins and breast cancer.

    Science.gov (United States)

    Pasqualini, Jorge R

    2007-10-01

    Progestins exert their progestational activity by binding to the progesterone receptor (form A, the most active and form B, the less active) and may also interact with other steroid receptors (androgen, glucocorticoid, mineralocorticoid, estrogen). They can have important effects in other tissues besides the endometrium, including the breast, liver, bone and brain. The biological responses of progestins cover a very large domain: lipids, carbohydrates, proteins, water and electrolyte regulation, hemostasis, fibrinolysis, and cardiovascular and immunological systems. At present, more than 200 progestin compounds have been synthesized, but the biological response could be different from one to another depending on their structure, metabolism, receptor affinity, experimental conditions, target tissue or cell line, as well as the biological response considered. There is substantial evidence that mammary cancer tissue contains all the enzymes responsible for the local biosynthesis of estradiol (E(2)) from circulating precursors. Two principal pathways are implicated in the final steps of E(2) formation in breast cancer tissue: the 'aromatase pathway', which transforms androgens into estrogens, and the 'sulfatase pathway', which converts estrone sulfate (E(1)S) into estrone (E(1)) via estrone sulfatase. The final step is the conversion of weak E(1) to the potent biologically active E(2) via reductive 17beta-hydroxysteroid dehydrogenase type 1 activity. It is also well established that steroid sulfotransferases, which convert estrogens into their sulfates, are present in breast cancer tissues. It has been demonstrated that various progestins (e.g. nomegestrol acetate, medrogestone, promegestone) as well as tibolone and their metabolites can block the enzymes involved in E(2) bioformation (sulfatase, 17beta-hydroxysteroid dehydrogenase) in breast cancer cells. These substances can also stimulate the sulfotransferase activity which converts estrogens into the biologically

  10. Breastfeeding, breast milk and viruses

    Directory of Open Access Journals (Sweden)

    Glenn Wendy K

    2007-10-01

    Full Text Available Abstract Background There is seemingly consistent and compelling evidence that there is no association between breastfeeding and breast cancer. An assumption follows that milk borne viruses cannot be associated with human breast cancer. We challenge this evidence because past breastfeeding studies did not determine "exposure" of newborn infants to colostrum and breast milk. Methods We conducted a prospective review of 100 consecutive births of infants in the same centre to determine the proportion of newborn infants who were "exposed" to colostrum or breast milk, as distinct from being fully breast fed. We also report a review of the breastfeeding practices of mothers of over 87,000 newborn infants in the Australian State of New South Wales. This study was approved by the Human Research Ethics Committee of the University of New South Wales (Sydney, Australia. Approval 05063, 29 September 2005. Results Virtually all (97 of 100 newborn infants in this centre were "exposed" to colostrum or breast milk whether or not they were fully breast fed. Between 82.2% to 98.7% of 87,000 newborn infants were "exposed" to colostrum or breast milk. Conclusion In some Western communities there is near universal exposure of new born infants to colostrum and breast milk. Accordingly it is possible for the transmission of human milk borne viruses. This is contrary to the widespread assumption that human milk borne viruses cannot be associated with breast cancer.

  11. For Women Facing a Breast Biopsy

    Science.gov (United States)

    ... Cancer Breast Cancer Early Detection and Diagnosis Breast Biopsy When other tests show that you might have ... before getting a breast biopsy. Fine needle aspiration biopsy In a fine needle aspiration (FNA) biopsy , a ...

  12. What Is Breast Cancer in Men?

    Science.gov (United States)

    ... and bloodstream. At least 8 out of 10 male breast cancers are IDCs (alone or mixed with other types ... is much smaller than the female breast, all male breast cancers start relatively close to the nipple, so they ...

  13. General Information about Breast Cancer and Pregnancy

    Science.gov (United States)

    ... Breast Cancer Treatment and Pregnancy (PDQ®)–Patient Version General Information about Breast Cancer and Pregnancy Go to ... are linked by thin tubes called ducts. Enlarge Anatomy of the female breast. The nipple and areola ...

  14. What to Expect After Breast Reconstruction Surgery

    Science.gov (United States)

    ... En Español Category Cancer A-Z Breast Cancer Breast Reconstruction Surgery Women who have surgery as part of ... and after your surgery. Deciding Whether To Have Breast Reconstruction Many women choose to have reconstruction surgery, but ...

  15. You, Your Teenage Daughter and Breast Cancer.

    Science.gov (United States)

    Brateman, Libby

    1991-01-01

    Discusses breast cancer and teenagers, focusing on how parents can introduce the subject and encourage breast self-examination. The article provides information on breast cancer statistics, mammography, and American Cancer Society services. (SM)

  16. Braving Breast Cancer: Just Do It!

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Breast Cancer Braving Breast Cancer: Just Do It! Past Issues / Spring - Summer 2010 Table of Contents Breast cancer survivor Jana Brightwell, pictured here on the NIH ...

  17. Abortion, Miscarriage, and Breast Cancer Risk

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Abortion, Miscarriage, and Breast Cancer Risk: 2003 Workshop In ... cancer risk, including studies of induced and spontaneous abortions. They concluded that having an abortion or miscarriage ...

  18. Transcription factors link mouse WAP-T mammary tumors with human breast cancer.

    Science.gov (United States)

    Otto, Benjamin; Streichert, Thomas; Wegwitz, Florian; Gevensleben, Heidrun; Klätschke, Kristin; Wagener, Christoph; Deppert, Wolfgang; Tolstonog, Genrich V

    2013-03-15

    Mouse models are important tools to decipher the molecular mechanisms of mammary carcinogenesis and to mimic the respective human disease. Despite sharing common phenotypic and genetic features, the proper translation of murine models to human breast cancer remains a challenging task. In a previous study we showed that in the SV40 transgenic WAP-T mice an active Met-pathway and epithelial-mesenchymal characteristics distinguish low- and high-grade mammary carcinoma. To assign these murine tumors to corresponding human tumors we here incorporated the analysis of expression of transcription factor (TF) coding genes and show that thereby a more accurate interspecies translation can be achieved. We describe a novel cross-species translation procedure and demonstrate that expression of unsupervised selected TFs, such as ELF5, HOXA5 and TFCP2L1, can clearly distinguish between the human molecular breast cancer subtypes--or as, for example, expression of TFAP2B between yet unclassified subgroups. By integrating different levels of information like histology, gene set enrichment, expression of differentiation markers and TFs we conclude that tumors in WAP-T mice exhibit similarities to both, human basal-like and non-basal-like subtypes. We furthermore suggest that the low- and high-grade WAP-T tumor phenotypes might arise from distinct cells of tumor origin. Our results underscore the importance of TFs as common cross-species denominators in the regulatory networks underlying mammary carcinogenesis.

  19. BREAST BIOMECANICAL MODELING FOR COMPRESSION OPTIMIZATION IN DIGITAL BREAST TOMOSYNTHESIS

    OpenAIRE

    Anna, Mîra; Carton, Ann-Katherine; Muller, Serge; Payan, Yohan

    2016-01-01

    International audience; The aim of this work is to develop a biomechanical Finite Element (FE) breast model in order to analyze different breast compression strategies and their impact on image quality. Large breast deformations will be simulated using this FE model. A particular attention will be granted to the computation of the initial stress in the model due to gravity and to boundary conditions imposed by the thorax anatomy. Finally, the model will be validated by comparing the estimated...

  20. Breast cancer fear in African American breast cancer survivors.

    Science.gov (United States)

    Gibson, Lynette M; Thomas, Sheila; Parker, Veronica; Mayo, Rachel; Wetsel, Margaret Ann

    2014-01-01

    The purpose of this study was to describe breast cancer fear according to phase of survivorship, determine whether breast cancer fear levels differed among survivorship phases, and determine the relationship between fear and age in African-American breast cancer survivors. The study utilized secondary data analysis from the study, Inner Resources as Predictors of Psychological Well-Being in AABCS. A new subscale entitled, "Breast Cancer Fear" was adapted from the Psychological Well Being Subscale by Ferrell and Grant. There was no significant difference between fear and phase of survivorship. There was a significant positive relationship between age and fear.

  1. Ultrasound screening of contralateral breast after surgery for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seung Ja [Department of Radiology, Seoul Metropolitan Government Seoul National University, Boramae Medical Center (Korea, Republic of); Chung, Se-Yeong; Chang, Jung Min; Cho, Nariya [Department of Radiology, Seoul National University Hospital (Korea, Republic of); Han, Wonshik [Department of Surgery, Seoul National University Hospital (Korea, Republic of); Moon, Woo Kyung, E-mail: moonwk@snu.ac.kr [Department of Radiology, Seoul National University Hospital (Korea, Republic of)

    2015-01-15

    Highlights: • The addition of supplemental US to mammography depicted additional 5.0 cancers per 1000 postoperative women. • Positive biopsy rate of mammography-detected lesions was 66.7% (4 of 6) and that of US-detected lesions was 40.0% (6 of 15). • US can be helpful to detect mammographically occult breast cancer in the contralateral breast in women with previous history of cancer and dense breast. - Abstract: Objective: To determine whether supplemental screening ultrasound (US) to mammography could improve cancer detection rate of the contralateral breast in patients with a personal history of breast cancer and dense breasts. Materials and methods: During a one-year study period, 1314 screening patients with a personal history of breast cancer and dense breasts simultaneously underwent mammography and breast US. BI-RADS categories were given for mammography or US-detected lesions in the contralateral breast. The reference standard was histology and/or 1-year imaging follow-up, and the cancer rate according to BI-RADS categories and cancer detection rate and positive biopsy rate according to detection modality were analyzed. Results: Of 1314 patients, 84 patients (6.4%) were categorized as category 3 with one interval cancer and one cancer which was upgraded to category 4A after 6-month follow-up US (2.5% cancer rate, 95% CIs 1.5–9.1%). Fifteen patients (1.1%) had category 4A or 4B lesions in the contralateral breast. Four lesions were detected on mammography (two lesions were also visible on US) and 11 lesions were detected on US and 5 cancers were confirmed (33.3%, 95% CIs 15.0–58.5%). Six patients (0.5%) had category 4C lesions, 2 detected on mammography and 4 on US and 4 cancers were confirmed (66.7%, 95% CIs 29.6–90.8%). No lesions were categorized as category 5 in the contralateral breast. Cancer detection rate by mammography was 3.3 per 1000 patients and that by US was 5.0 per 1000 patients, therefore overall cancer detection rate by

  2. Breast-feeding after breast cancer: if you wish, madam.

    Science.gov (United States)

    Azim, Hatem A; Bellettini, Giulia; Gelber, Shari; Peccatori, Fedro A

    2009-03-01

    Breast cancer is the most common malignant tumor-affecting women during the child bearing period. With the rising trend in delaying pregnancy later in life, the issue of subsequent pregnancy and lactation following breast cancer diagnosis has been more frequently encountered. In this context, data is scarce particularly those addressing the issue of lactation. In this review, we discussed different endocrinal, clinical and biological aspects dealing with breast-feeding after breast cancer in an attempt to determine how safe and feasible this approach is.

  3. Breast Imaging after Breast Augmentation with Autologous Tissues

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Kyu Won; Seo, Bo Kyung; Shim, Eddeum; Song, Sung Eun; Cho, Kyu Ran [Dept. of Radiology, Korea University Anam Hospital, Seoul (Korea, Republic of); Yoon, Eul Sik [Korea University Ansan Hospital, Ansan (Korea, Republic of); Woo, Ok Hee [Dept. of Radiology, Korea University Guro Hospital, Seoul (Korea, Republic of)

    2012-06-15

    The use of autologous tissue transfer for breast augmentation is an alternative to using foreign implant materials. The benefits of this method are the removal of unwanted fat from other body parts, no risk of implant rupture, and the same feel as real breast tissue. However, sometimes there is a dilemma about whether or not to biopsy for calcifications or masses detected after the procedure is completed. The purpose of this study is to illustrate the procedures of breast augmentation with autologous tissues, the imaging features of various complications, and the role of imaging in the diagnosis and management of complications and hidden breast diseases.

  4. Opioids and breast cancer recurrence

    DEFF Research Database (Denmark)

    Cronin-Fenton, Deirdre P; Heide-Jørgensen, Uffe; Ahern, Thomas P

    2015-01-01

    BACKGROUND: Opioids may alter immune function, thereby potentially affecting cancer recurrence. The authors investigated the association between postdiagnosis opioid use and breast cancer recurrence. METHODS: Patients with incident, early stage breast cancer who were diagnosed during 1996 through...... 2008 in Denmark were identified from the Danish Breast Cancer Cooperative Group Registry. Opioid prescriptions were ascertained from the Danish National Prescription Registry. Follow-up began on the date of primary surgery for breast cancer and continued until breast cancer recurrence, death......, emigration, 10 years, or July 31, 2013, whichever occurred first. Cox regression models were used to compute hazard ratios and 95% confidence intervals associating breast cancer recurrence with opioid prescription use overall and by opioid type and strength, immunosuppressive effect, chronic use (≥6 months...

  5. Interleukin-19 in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ying-Yin Chen

    2013-01-01

    Full Text Available Inflammatory cytokines within the tumor microenvironment are linked to progression in breast cancer. Interleukin- (IL- 19, part of the IL-10 family, contributes to a range of diseases and disorders, such as asthma, endotoxic shock, uremia, psoriasis, and rheumatoid arthritis. IL-19 is expressed in several types of tumor cells, especially in squamous cell carcinoma of the skin, tongue, esophagus, and lung and invasive duct carcinoma of the breast. In breast cancer, IL-19 expression is correlated with increased mitotic figures, advanced tumor stage, higher metastasis, and poor survival. The mechanisms of IL-19 in breast cancer have recently been explored both in vitro and in vivo. IL-19 has an autocrine effect in breast cancer cells. It directly promotes proliferation and migration and indirectly provides a microenvironment for tumor progression, which suggests that IL-19 is a prognostic marker in breast cancer and that antagonizing IL-19 may have therapeutic potential.

  6. Breast Abscess: A Brief Communication

    Directory of Open Access Journals (Sweden)

    Pradipta Das

    2017-07-01

    Full Text Available Breast infections commonly affect women aged between 18 and 50 years and are categorized as lactational and non-lactational infections. The infection can affect the skin overlying the breast when it can be a primary event or, it may occur secondary to mastitis and/or, secondary to a lesion in the skin. The commoner clinical findings consist of a tender, hard breast mass with erythema of the overlying skin. Needle aspiration yields pus cultures of which yield the infecting microorganisms. In practice, treatment is usually empiric consisting of bed rest, frequent nursing, fluids, Acetaminophen for pain and fever and a course of antibiotics. The other common line of treatment for breast abscess consists of incision and drainage with primary and/or, secondary closure. This brief communication on breast abscess gives an overview of the possible etiologies, clinical signs and symptoms and the treatment lines for breast abscess.

  7. Breast manifestations of systemic diseases

    Directory of Open Access Journals (Sweden)

    Dilaveri CA

    2012-02-01

    Full Text Available Christina A Dilaveri, Maire Brid Mac Bride, Nicole P Sandhu, Lonzetta Neal, Karthik Ghosh, Dietlind L Wahner-RoedlerDivision of General Internal Medicine, Mayo Clinic, Rochester, MN, USAAbstract: Although much emphasis has been placed on the primary presentations of breast cancer, little focus has been placed on how systemic illnesses may affect the breast. In this article, we discuss systemic illnesses that can manifest in the breast. We summarize the clinical features, imaging, histopathology, and treatment recommendations for endocrine, vascular, systemic inflammatory, infectious, and hematologic diseases, as well as for the extramammary malignancies that can present in the breast. Despite the rarity of these manifestations of systemic disease, knowledge of these conditions is critical to the appropriate evaluation and treatment of patients presenting with breast symptoms.Keywords: breast, endocrine, hematologic, infectious, vascular

  8. Extreme oncoplastic breast surgery: A case report

    Directory of Open Access Journals (Sweden)

    Daniele Bordoni

    2016-01-01

    Conclusion: The surgical treatment for multicentric breast cancers remains controversial even though emerging evidences show good oncological and aesthetic outcomes following oncoplastic conserving breast surgery.

  9. Ly6E/K Signaling to TGFβ Promotes Breast Cancer Progression, Immune Escape, and Drug Resistance.

    Science.gov (United States)

    AlHossiny, Midrar; Luo, Linlin; Frazier, William R; Steiner, Noriko; Gusev, Yuriy; Kallakury, Bhaskar; Glasgow, Eric; Creswell, Karen; Madhavan, Subha; Kumar, Rakesh; Upadhyay, Geeta

    2016-06-01

    Stem cell antigen Sca-1 is implicated in murine cancer stem cell biology and breast cancer models, but the role of its human homologs Ly6K and Ly6E in breast cancer are not established. Here we report increased expression of Ly6K/E in human breast cancer specimens correlates with poor overall survival, with an additional specific role for Ly6E in poor therapeutic outcomes. Increased expression of Ly6K/E also correlated with increased expression of the immune checkpoint molecules PDL1 and CTLA4, increased tumor-infiltrating T regulatory cells, and decreased natural killer (NK) cell activation. Mechanistically, Ly6K/E was required for TGFβ signaling and proliferation in breast cancer cells, where they contributed to phosphorylation of Smad1/5 and Smad2/3. Furthermore, Ly6K/E promoted cytokine-induced PDL1 expression and activation and binding of NK cells to cancer cells. Finally, we found that Ly6K/E promoted drug resistance and facilitated immune escape in this setting. Overall, our results establish a pivotal role for a Ly6K/E signaling axis involving TGFβ in breast cancer pathophysiology and drug response, and highlight this signaling axis as a compelling realm for therapeutic invention. Cancer Res; 76(11); 3376-86. ©2016 AACR. ©2016 American Association for Cancer Research.

  10. In vivo imaging of human breast cancer mouse model with high level expression of calcium sensing receptor at 3T.

    Science.gov (United States)

    Baio, Gabriella; Fabbi, Marina; Emionite, Laura; Cilli, Michele; Salvi, Sandra; Ghedin, Piero; Prato, Sabina; Carbotti, Grazia; Tagliafico, Alberto; Truini, Mauro; Neumaier, Carlo Emanuele

    2012-03-01

    To demonstrate that manganese can visualise calcium sensing receptor (CaSR)-expressing cells in a human breast cancer murine model, as assessed by clinical 3T magnetic resonance (MR). Human MDA-MB-231-Luc or MCF7-Luc breast cancer cells were orthotopically grown in NOD/SCID mice to a minimum mass of 5 mm. Mice were evaluated on T1-weighted sequences before and after intravenous injection of MnCl(2). To block the CaSR-activated Ca(2+) channels, verapamil was injected at the tumour site 5 min before Mn(2+) administration. CaSR expression in vivo was studied by immunohistochemistry. Contrast enhancement was observed at the tumour periphery 10 min after Mn(2+) administration, and further increased up to 40 min. In verapamil-treated mice, no contrast enhancement was observed. CaSR was strongly expressed at the tumour periphery. Manganese enhanced magnetic resonance imaging can visualise CaSR-expressing breast cancer cells in vivo, opening up possibilities for a new MR contrast agent. • Manganese contrast agents helped demonstrate breast cancer cells in an animal model. • Enhancement was most marked in cells with high calcium sensing receptor expression. • Manganese uptake was related to the distribution of CaSR within the tumour. • Manganese MRI may become useful to investigate human breast cancer.

  11. Biomarkers in Tissue Samples From Patients With Newly Diagnosed Breast Cancer Treated With Zoledronic Acid

    Science.gov (United States)

    2016-07-12

    Estrogen Receptor-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Progesterone Receptor-positive Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

  12. Bioenergy and Breast Cancer: A Report on Tumor Growth and Metastasis.

    Science.gov (United States)

    Running, Alice; Greenwood, Mark; Hildreth, Laura; Schmidt, Jade

    2016-01-01

    As many as 80% of the 296,000 women and 2,240 men diagnosed with breast cancer in the United States will seek out complementary and alternative medicine (CAM) treatments. One such therapy is Healing Touch (HT), recognized by the National Center for Complementary and Integrative Health (NCCIH) as a treatment modality. Using a multiple experimental groups design, fifty-six six- to eight-week-old Balb/c mice were injected with 4T1 breast cancer tumor cells and randomly divided into intervention and positive control groups. Five days after tumor cell injection, mice in the intervention groups received HT either daily or every other day for 10 minutes by one HT practitioner. At 15 days after tumor cell injection, tumor size was measured, and metastasis was evaluated by a medical pathologist after necropsy. Tumor size did not differ significantly among the groups (F(3,52) = 0.75, p value = 0.53). The presence of metastasis did not differ across groups (chi-square(3) = 3.902, p = 0.272) or when compared within an organ (liver: chi-square(3) = 2.507, p = 0.474; lungs: chi-square(3) = 3.804, p = 0.283; spleen: chi-square(3) = 0.595, p = 0.898). However, these results did indicate a moderate, though insignificant, positive impact of HT and highlight the need for continued research into dose, length of treatment, and measurable outcomes (tumor size, metastasis) to provide evidence to suggest application for nursing care.

  13. Mitochondrial Localized Stat3 Promotes Breast Cancer Growth via Phosphorylation of Serine 727*

    Science.gov (United States)

    Zhang, Qifang; Raje, Vidisha; Yakovlev, Vasily A.; Yacoub, Adly; Szczepanek, Karol; Meier, Jeremy; Derecka, Marta; Chen, Qun; Hu, Ying; Sisler, Jennifer; Hamed, Hossein; Lesnefsky, Edward J.; Valerie, Kristoffer; Dent, Paul; Larner, Andrew C.

    2013-01-01

    Signal transducer and activator of transcription 3 (Stat3) is a key mediator in the development of many cancers. For 20 years, it has been assumed that Stat3 mediates its biological activities as a nuclear localized transcription factor activated by many cytokines. However, recent studies from this laboratory and others indicate that Stat3 has an independent function in the mitochondria (mitoStat3) where it controls the activity of the electron transport chain (ETC) and mediates Ras-induced transformation of mouse embryo fibroblasts. The actions of mitoStat3 in controlling respiration and Ras transformation are mediated by the phosphorylation state of serine 727. To address the role of mitoStat3 in the pathogenesis of cells that are transformed, we used 4T1 breast cancer cells, which form tumors that metastasize in immunocompetent mice. Substitution of Ser-727 for an alanine or aspartate in Stat3 that has a mitochondrial localization sequence, MLS-Stat3, has profound effects on tumor growth, complex I activity of the ETC, and accumulation of reactive oxygen species (ROS). Cells expressing MLS-Stat3(S727A) display slower tumor growth, decreased complex I activity of the ETC, and increased ROS accumulation under hypoxia compared with cells expressing MLS-Stat3. In contrast, cells expressing MLS-Stat3(S727D) show enhanced tumor growth and complex I activity and decreased production of ROS. These results highlight the importance of serine 727 of mitoStat3 in breast cancer and suggest a novel role for mitoStat3 in regulation of ROS concentrations through its action on the ETC. PMID:24019511

  14. OP449 inhibits breast cancer growth without adverse metabolic effects.

    Science.gov (United States)

    Shlomai, Gadi; Zelenko, Zara; Antoniou, Irini Markella; Stasinopoulos, Marilyn; Tobin-Hess, Aviva; Vitek, Michael P; LeRoith, Derek; Gallagher, Emily Jane

    2017-10-01

    Hyperinsulinemia is associated with a decrease in breast cancer recurrence-free survival and overall survival. Inhibition of insulin receptor signaling is associated with glycemic dysregulation. SET is a direct modulator of PP2A, which negatively regulates the PI3K/AKT/mTOR pathway. OP449, a SET inhibitor, decreases AKT/mTOR activation. The effects of OP449 treatment on breast cancer growth in the setting of pre-diabetes, and its metabolic implications are currently unknown. We found that the volumes and weights of human MDA-MB-231 breast cancer xenografts were greater in hyperinsulinemic mice compared with controls (P < 0.05), and IR phosphorylation was 4.5-fold higher in these mice (P < 0.05). Human and murine breast cancer tumors treated with OP449 were 47% and 39% smaller than controls (P < 0.05, for both, respectively). AKT and S6RP phosphorylation were 82% and 34% lower in OP449-treated tumors compared with controls (P < 0.05, P = 0.06, respectively). AKT and S6RP phosphorylation in response to insulin was 30% and 12% lower in cells, pre-treated with OP449, compared with control cells (P < 0.01, P < 0.05, respectively). However, even with decreased AKT/mTOR activation, body weights and composition, blood glucose and plasma insulin, glucose tolerance, serum triglyceride and cholesterol levels were similar between OP449-treated mice and controls. Xenografts and liver tissue from OP449-treated mice showed a 64% and 70% reduction in STAT5 activation, compared with controls (P < 0.01 and P = 0.06, respectively). Our data support an anti-neoplastic effect of OP449 on human breast cancer cells in vitro and in xenografts in the setting of hyperinsulinemia. OP449 led to the inhibition of AKT/mTOR signaling, albeit, not leading to metabolic derangements. © 2017 Society for Endocrinology.

  15. Progress in breast cancer: overview.

    Science.gov (United States)

    Arteaga, Carlos L

    2013-12-01

    This edition of CCR Focus titled Research in Breast Cancer: Frontiers in Genomics, Biology, and Clinical Investigation reviews six topics that cover areas of translational research of high impact in breast cancer. These topics represent areas of breast cancer research where significant progress has occurred but also where very important challenges remain. The papers in this CCR Focus section are contributed by experts in the respective areas of investigation. Herein, key aspects of these contributions and the research directions they propose are reviewed.

  16. Aluminium, antiperspirants and breast cancer.

    Science.gov (United States)

    Darbre, P D

    2005-09-01

    Aluminium salts are used as the active antiperspirant agent in underarm cosmetics, but the effects of widespread, long term and increasing use remain unknown, especially in relation to the breast, which is a local area of application. Clinical studies showing a disproportionately high incidence of breast cancer in the upper outer quadrant of the breast together with reports of genomic instability in outer quadrants of the breast provide supporting evidence for a role for locally applied cosmetic chemicals in the development of breast cancer. Aluminium is known to have a genotoxic profile, capable of causing both DNA alterations and epigenetic effects, and this would be consistent with a potential role in breast cancer if such effects occurred in breast cells. Oestrogen is a well established influence in breast cancer and its action, dependent on intracellular receptors which function as ligand-activated zinc finger transcription factors, suggests one possible point of interference from aluminium. Results reported here demonstrate that aluminium in the form of aluminium chloride or aluminium chlorhydrate can interfere with the function of oestrogen receptors of MCF7 human breast cancer cells both in terms of ligand binding and in terms of oestrogen-regulated reporter gene expression. This adds aluminium to the increasing list of metals capable of interfering with oestrogen action and termed metalloestrogens. Further studies are now needed to identify the molecular basis of this action, the longer term effects of aluminium exposure and whether aluminium can cause aberrations to other signalling pathways in breast cells. Given the wide exposure of the human population to antiperspirants, it will be important to establish dermal absorption in the local area of the breast and whether long term low level absorption could play a role in the increasing incidence of breast cancer.

  17. Male Breast Adenoid Cystic Carcinoma

    Directory of Open Access Journals (Sweden)

    Seung Jin Yoo

    2013-10-01

    Full Text Available Introduction: Adenoid cystic carcinoma (ACC of the breast is a rare condition, and cases in male patients are even less common. Case: We describe a case of ACC of the breast with axillary lymph node metastasis, disseminated osteolytic bone metastasis and bone marrow involvement in a 41-year-old man. Conclusion: Male breast ACC is an extremely rare malignancy; there can be difficulty in obtaining a final diagnosis. We report this case because of its rarity.

  18. Circadian clocks and breast cancer

    OpenAIRE

    Blakeman, Victoria; Jack L. Williams; Meng, Qing-Jun; Streuli, Charles H

    2016-01-01

    Circadian clocks respond to environmental time cues to coordinate 24-hour oscillations in almost every tissue of the body. In the breast, circadian clocks regulate the rhythmic expression of numerous genes. Disrupted expression of circadian genes can alter breast biology and may promote cancer. Here we overview circadian mechanisms, and the connection between the molecular clock and breast biology. We describe how disruption of circadian genes contributes to cancer via multiple mechanisms, an...

  19. Breastfeeding, breast milk and viruses

    OpenAIRE

    Glenn Wendy K; Heads Joy; Lawson James S; Whitaker Noel J

    2007-01-01

    Abstract Background There is seemingly consistent and compelling evidence that there is no association between breastfeeding and breast cancer. An assumption follows that milk borne viruses cannot be associated with human breast cancer. We challenge this evidence because past breastfeeding studies did not determine "exposure" of newborn infants to colostrum and breast milk. Methods We conducted a prospective review of 100 consecutive births of infants in the same centre to determine the propo...

  20. UBMD (untitled breast milk drawings

    Directory of Open Access Journals (Sweden)

    Margaret Morgan

    2013-01-01

    Full Text Available 'UBMD' (2002-present by Margaret Morgan is a series of untitled breast milk drawings rendered in pencil, gouache and human breast milk. The drawings combine two representational systems, the indexical and the mimetic, to appropriate Rosalind Krauss' terms on photography: Milk squirted directly from the artist's breast leaves a dark trace of lines, drips and splashes, a direct record of the action, an index no less immediate than the action of light on a photosensitive surface.

  1. [Organized breast cancer screening].

    Science.gov (United States)

    Rouëssé, Jacques; Sancho-Garnier, Hélèn

    2014-02-01

    Breast screening programs are increasingly controversial, especially regarding two points: the number of breast cancer deaths they avoid, and the problem of over-diagnosis and over-treatment. The French national breast cancer screening program was extended to cover the whole country in 2004. Ten years later it is time to examine the risk/benefit ratio of this program and to discuss the need for change. Like all forms of cancer management, screening must be regularly updated, taking into account the state of the art, new evidence, and uncertainties. All screening providers should keep themselves informed of the latest findings. In the French program, women aged 50-74 with no major individual or familial risk factors for breast cancer are offered screening mammography and clinical breast examination every two years. Images considered non suspicious of malignancy by a first reader are re-examined by a second reader. The devices and procedures are subjected to quality controls. Participating radiologists (both public and private) are required to read at least 500 mammographies per year. The program's national participation rate was 52.7 % in 2012. When individual screening outside of the national program is taken into account (nearly 15 % of women), coverage appears close to the European recommendation of 65 %. Breast cancer mortality has been falling in France by 0.6 % per year for over 30 years, starting before mass screening was implemented, and by 1.5 % since 2005. This decline can be attributed in part to earlier diagnosis and better treatment, so that the specific impact of screening cannot easily be measured. Over-treatment, defined as the detection and treatment of low-malignancy tumors that would otherwise not have been detected in a person's lifetime, is a major negative effect of screening, but its frequency is not precisely known (reported to range from 1 % to 30 %). In view of these uncertainties, it would be advisable to modify the program in order to

  2. Unemployment among breast cancer survivors.

    Science.gov (United States)

    Carlsen, Kathrine; Ewertz, Marianne; Dalton, Susanne Oksbjerg; Badsberg, Jens Henrik; Osler, Merete

    2014-05-01

    Though about 20% of working age breast cancer survivors do not return to work after treatment, few studies have addressed risk factors for unemployment. The majority of studies on occupational consequences of breast cancer focus on non-employment, which is a mixture of sickness absence, unemployment, retirement pensions and other reasons for not working. Unemployment in combination with breast cancer may represent a particular challenge for these women. The aim of the present study is therefore to analyze the risk for unemployment in the years following diagnosis and treatment for breast cancer. This study included 14,750 women diagnosed with breast cancer in Denmark 2001-2009 identified through a population-based clinical database and linked with information from Danish administrative population based registers for information on labour market affiliation, socio-demography and co-morbid conditions. Multivariable analyses were performed by Cox's proportional hazard models. Two years after treatment, 81% of patients were still part of the work force, 10% of which were unemployed. Increasing duration of unemployment before breast cancer was associated with an adjusted HR = 4.37 (95% CI: 3.90-4.90) for unemployment after breast cancer. Other risk factors for unemployment included low socioeconomic status and demography, while adjuvant therapy did not increase the risk of unemployment. Duration of unemployment before breast cancer was the most important determinant of unemployment after breast cancer treatment. This allows identification of a particularly vulnerable group of patients in need of rehabilitation.

  3. Breast health in developing countries.

    Science.gov (United States)

    Yip, C H; Taib, N A

    2014-12-01

    Breast cancer is one of the leading cancers world-wide. While the incidence in developing countries is lower than in developed countries, the mortality is much higher. Of the estimated 1 600 000 new cases of breast cancer globally in 2012, 794 000 were in the more developed world compared to 883 000 in the less developed world; however, there were 198 000 deaths in the more developed world compared to 324 000 in the less developed world (data from Globocan 2012, IARC). Survival from breast cancer depends on two main factors--early detection and optimal treatment. In developing countries, women present with late stages of disease. The barriers to early detection are physical, such as geographical isolation, financial as well as psychosocial, including lack of education, belief in traditional medicine and lack of autonomous decision-making in the male-dominated societies that prevail in the developing world. There are virtually no population-based breast cancer screening programs in developing countries. However, before any screening program can be implemented, there must be facilities to treat the cancers that are detected. Inadequate access to optimal treatment of breast cancer remains a problem. Lack of specialist manpower, facilities and anticancer drugs contribute to the suboptimal care that a woman with breast cancer in a low-income country receives. International groups such as the Breast Health Global Initiative were set up to develop economically feasible, clinical practice guidelines for breast cancer management to improve breast health outcomes in countries with limited resources.

  4. Proteomic classification of breast cancer.

    LENUS (Irish Health Repository)

    Kamel, Dalia

    2012-11-01

    Being a significant health problem that affects patients in various age groups, breast cancer has been extensively studied to date. Recently, molecular breast cancer classification has advanced significantly with the availability of genomic profiling technologies. Proteomic technologies have also advanced from traditional protein assays including enzyme-linked immunosorbent assay, immunoblotting and immunohistochemistry to more comprehensive approaches including mass spectrometry and reverse phase protein lysate arrays (RPPA). The purpose of this manuscript is to review the current protein markers that influence breast cancer prediction and prognosis and to focus on novel advances in proteomic classification of breast cancer.

  5. Vitamin D Deficiency in Human and Murine Sepsis*

    Science.gov (United States)

    Parekh, Dhruv; Patel, Jaimin M.; Scott, Aaron; Lax, Sian; Dancer, Rachel C. A.; D’Souza, Vijay; Greenwood, Hannah; Fraser, William D.; Gao, Fang; Sapey, Elizabeth; Perkins, Gavin D.

    2017-01-01

    Objectives: Vitamin D deficiency has been implicated as a pathogenic factor in sepsis and ICU mortality but causality of these associations has not been demonstrated. To determine whether sepsis and severe sepsis are associated with vitamin D deficiency and to determine whether vitamin D deficiency influences the severity of sepsis. Design, Setting, and Patients: Sixty-one patients with sepsis and severe sepsis from two large U.K. hospitals and 20 healthy controls were recruited. Murine models of cecal ligation and puncture and intratracheal lipopolysaccharide were undertaken in normal and vitamin D deficient mice to address the issue of causality. Measurements and Main Results: Patients with severe sepsis had significantly lower concentrations of 25-hydroxyvitamin D3 than patients with either mild sepsis or age-matched healthy controls (15.7 vs 49.5 vs 66.5 nmol/L; p = 0.0001). 25-hydroxyvitamin D3 concentrations were significantly lower in patients who had positive microbiologic culture than those who were culture negative (p = 0.0023) as well as those who died within 30 days of hospital admission (p = 0.025). Vitamin D deficiency in murine sepsis was associated with increased peritoneal (p = 0.037), systemic (p = 0.019), and bronchoalveolar lavage (p = 0.011) quantitative bacterial culture. This was associated with reduced local expression of the cathelicidin-related antimicrobial peptide as well as evidence of defective macrophage phagocytosis (p = 0.029). In the intratracheal lipopolysaccharide model, 1,500 IU of intraperitoneal cholecalciferol treatment 6 hours postinjury reduced alveolar inflammation, cellular damage, and hypoxia. Conclusions: Vitamin D deficiency is common in severe sepsis. This appears to contribute to the development of the condition in clinically relevant murine models and approaches to correct vitamin D deficiency in patients with sepsis should be developed. PMID:27632669

  6. Characterization of a Novel Murine Model to Study Zika Virus

    Science.gov (United States)

    Rossi, Shannan L.; Tesh, Robert B.; Azar, Sasha R.; Muruato, Antonio E.; Hanley, Kathryn A.; Auguste, Albert J.; Langsjoen, Rose M.; Paessler, Slobodan; Vasilakis, Nikos; Weaver, Scott C.

    2016-01-01

    The mosquito-borne Zika virus (ZIKV) is responsible for an explosive ongoing outbreak of febrile illness across the Americas. ZIKV was previously thought to cause only a mild, flu-like illness, but during the current outbreak, an association with Guillain–Barré syndrome and microcephaly in neonates has been detected. A previous study showed that ZIKV requires murine adaptation to generate reproducible murine disease. In our study, a low-passage Cambodian isolate caused disease and mortality in mice lacking the interferon (IFN) alpha receptor (A129 mice) in an age-dependent manner, but not in similarly aged immunocompetent mice. In A129 mice, viremia peaked at ∼107 plaque-forming units/mL by day 2 postinfection (PI) and reached high titers in the spleen by day 1. ZIKV was detected in the brain on day 3 PI and caused signs of neurologic disease, including tremors, by day 6. Robust replication was also noted in the testis. In this model, all mice infected at the youngest age (3 weeks) succumbed to illness by day 7 PI. Older mice (11 weeks) showed signs of illness, viremia, and weight loss but recovered starting on day 8. In addition, AG129 mice, which lack both type I and II IFN responses, supported similar infection kinetics to A129 mice, but with exaggerated disease signs. This characterization of an Asian lineage ZIKV strain in a murine model, and one of the few studies reporting a model of Zika disease and demonstrating age-dependent morbidity and mortality, could provide a platform for testing the efficacy of antivirals and vaccines. PMID:27022155

  7. Forced recombination of psi-modified murine leukaemia virus-based vectors with murine leukaemia-like and VL30 murine endogenous retroviruses

    DEFF Research Database (Denmark)

    Mikkelsen, J G; Lund, Anders Henrik; Duch, M;

    1999-01-01

    -impaired Akv-MLV-derived vectors, we here examine putative genetic interactions between vector RNAs and copackaged endogenous retroviral RNAs of the murine leukaemia virus (MLV) and VL30 retroelement families. We show (i) that MLV recombination is not blocked by nonhomology within the 5' untranslated region...... harbouring the supposed RNA dimer-forming cis -elements and (ii) that copackaged retroviral RNAs can recombine despite pronounced sequence dissimilarity at the cross-over site(s) and within parts of the genome involved in RNA dimerization, encapsidation and strand transferring during reverse transcription....... We note that recombination-based rescue of primer binding site knock-out retroviral vectors may constitute a sensitive assay to register putative genetic interactions involving endogenous retroviral RNAs present in cells of various species....

  8. Timing of chemotherapy and surgery in a murine osteosarcoma model.

    Science.gov (United States)

    Bell, R S; Roth, Y F; Gebhardt, M C; Bell, D F; Rosenberg, A E; Mankin, H J; Suit, H D

    1988-10-01

    The sequential use of chemotherapy and surgery in the treatment of osteosarcoma developed in an empirical fashion without the benefit of investigations in animal models. The MGH-OGS murine osteosarcoma is a transplantable tumor that resembles the human disease with respect to histology, local invasiveness, metastatic characteristics, tumor ploidy, and its response to chemotherapy. We have used this tumor model to investigate the efficacy of preoperative, perioperative, and postoperative chemotherapy on the development of pulmonary metastases in three different experimental protocols. In each experimental design, perioperative chemotherapy demonstrated a significant advantage in preventing systemic relapse.

  9. Investigation of Murine Models for Sleep, Wakefulness and Target Discovery

    Science.gov (United States)

    2007-10-01

    subjective day, 7pm-7am w R NR 0 50 100 150 200 250 state c o u n t s F2 Females F2 Males Different from humans, mice exhibit polyphasic sleep with many...early trends, e.g., in the 1p.m. (6 hrs of subjective night) group, became non-significant with additional mice tested • The polyphasic sleep ...REPORT Final report - Investigation of Murine Models for Sleep , Wakefulness and Target Discovery 14. ABSTRACT 16. SECURITY CLASSIFICATION OF

  10. Adrenaline influences the release of interleukin-6 from murine pituicytes

    DEFF Research Database (Denmark)

    Christensen, J D; Hansen, E W; Frederiksen, C

    1999-01-01

    In this study, we examined the effect of adrenaline and interleukin-1beta on interleukin-6 secretion from cultured murine neurohypophyseal cells. Cells were cultured from neurohypophyses of 3- to 5-week-old mice and experiments were performed after 13 days in culture. Interleukin-6 was measured...... in 24-h samples using a sandwich fluoroimmunoassay. Unstimulated cells released 19+/-3 fmol interleukin-6/neurohypophysis/24 h (mean +/- S.E.M., n = 42). Adrenaline and interleukin-1beta increased the release of interleukin-6 from the cells in a concentration-dependent manner. Incubation with adrenaline...

  11. Drosophila homolog of the murine Int-1 protooncogene.

    OpenAIRE

    1988-01-01

    We have isolated phage clones from Drosophila melanogaster genomic and cDNA libraries containing a sequence homologous to the murine Int-1 protooncogene. The Drosophila gene is represented by a single locus at position 28A1-2 on chromosome 2. The gene is expressed as a 2.9-kilobase-long polyadenylylated mRNA in embryo, larval, and pupal stages. It is hardly detectable in adult flies. The longest open reading frame of the cDNA clone corresponds to a protein 469 amino acids long. Alignment of t...

  12. Sexual transmission of Trypanosoma cruzi in murine model.

    Science.gov (United States)

    Ribeiro, Marcelle; Nitz, Nadjar; Santana, Camilla; Moraes, Aline; Hagström, Luciana; Andrade, Rafael; Rios, Adriano; Sousa, Alessandro; Dallago, Bruno; Gurgel-Gonçalves, Rodrigo; Hecht, Mariana

    2016-03-01

    Trypanosoma cruzi is mainly transmitted by blood-sucking triatomines, but other routes also have epidemiological importance, such as blood transfusion and congenital transmission. Although the possibility of sexual transmission of T. cruzi has been suggested since its discovery, few studies have been published on this subject. We investigated acquisition of T. cruzi by sexual intercourse in an experimental murine model. Male and female mice in the chronic phase of Chagas disease were mated with naive partners. Parasitological, serological and molecular tests demonstrated the parasites in tissues and blood of partners. These results confirm the sexual transmission of T. cruzi in mice.

  13. Anticonvulsive evaluation of THIP in the murine pentylenetetrazole kindling model

    DEFF Research Database (Denmark)

    Simonsen, Charlotte; Boddum, Kim; von Schoubye, Nadia L

    2017-01-01

    . Evaluation of THIP as a potential anticonvulsant has given contradictory results in different animal models and for this reason, we reevaluated the anticonvulsive properties of THIP in the murine pentylenetetrazole (PTZ) kindling model. As loss of δ-GABAA R in the dentate gyrus has been associated...... the observed upregulation of δ-GABAA Rs. Even in the demonstrated presence of functional δ-GABAA Rs, THIP (0.5-4 mg/kg) showed no anticonvulsive effect in the PTZ kindling model using a comprehensive in vivo evaluation of the anticonvulsive properties....

  14. Using mastectomy specimens to develop breast models for breast tomosynthesis and CT breast imaging

    Science.gov (United States)

    O'Connor, J. Michael; Das, Mini; Didier, Clay; Mah'D, Mufeed; Glick, Stephen J.

    2008-03-01

    Dedicated x-ray computed tomography (CT) of the breast using a cone-beam flat-panel detector system is a modality under investigation by a number of research teams. As previously reported, we have fabricated a prototype, bench-top flat-panel CT breast imaging (CTBI) system and developed computer simulation software to model such a system. We are developing a methodology to use high resolution, low noise CT reconstructions of fresh mastectomy specimens for generating an ensemble of 3D digital breast phantoms that realistically model 3D compressed and uncompressed breast anatomy. These breast models can be used to simulate realistic projection data for both breast tomosynthesis (BT) and CT systems thereby providing a powerful evaluation and optimization mechanism.

  15. Staphylococcal enterotoxin B/texosomes as a candidate for breast cancer immunotherapy.

    Science.gov (United States)

    Imani Fooladi, Abbas Ali; Halabian, Raheleh; Mahdavi, Mehdi; Amin, Mohsen; Mahmoodzadeh Hosseini, Hamideh

    2016-01-01

    A new recombinant construct made up of two components, texosomes (TEX) and staphylococcal enterotoxin B (SEB), showed cytostatic properties against several types of tumor cells in vitro. Here, we aimed to assess the construct's antitumor immunogenicity in a murine tumor model. SEB was anchored onto purified texosomes and was used for immunization of mice before challenge with 4T1 cells. Tumor size, survival time, necrosis, metastasis rate, and the levels of IL-2, IL-4, IL-17, IL-12, TNF-α, and IFN-γ were measured. Immunization of the mice with TEX-SEB increased the stimulation index of splenocytes significantly compared with the PBS-treated mice (p < 0.01). In addition, there was a significant increase of TNF-α, IL-2, and IFN-γ secreted from isolated splenocytes of the mice immunized by either TEX-SEB, TEX + SEB, TEX, or SEB in comparison with PBS (p < 0.001, p < 0.001, and p < 0.05, respectively), whereas no significant change of IL-4 secretion was observed in any treated groups. Finding from tumor tissue homogenate testing showed that the level of IL-17 and IFN-γ among mice immunized with TEX-SEB was significantly lower than PBS-treated group (p < 0.05). IL-12, IL-4, and TNF-α levels were not significantly different from PBS- and TEX-SEB-immunized groups except in the SEB-immunized mice. Although TEX-SEB immunization relatively prolonged the survival of the mice, it had no inhibitory impact on tumor size. Pathologic manifestations showed the significant rise of necrosis after immunization with TEX-SEB compared to PBS (p < 0.01). Overall, our findings suggest that the presence of SEB rescues tumorigenesis effects of TEX making the construct an appropriate candidate for tumor immunotherapy.

  16. Metoclopramide and breast milk.

    Science.gov (United States)

    de Gezelle, H; Ooghe, W; Thiery, M; Dhont, M

    1983-04-01

    Thirteen primiparous nursing mothers participated in this placebo-controlled double blind trial of metoclopramide. Therapy was started on the first postpartum day and continued for 8 days. Seven women received metoclopramide (10 mg, 3 X dd). Serum prolactin and milk yield were measured during the trial. The breast milk composition was analysed during the trial and weekly for 3 wk after the trial. A detailed analysis of the amino acid content was performed on the 6th and 21st postpartum days. During the early puerperium the total milk yield was ca. 50% greater in the metoclopramide-treated group compared to the control group. The evolution of the breast milk composition was similar for both groups, except for the amino acid content. The shift in amino acid composition occurred earlier in the treatment group indicating that metoclopramide enhances the rate of transition from colostrum to mature milk.

  17. Viruses and Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lawson, James S., E-mail: james.lawson@unsw.edu.au; Heng, Benjamin [School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney (Australia)

    2010-04-30

    Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify viruses which may have a role in breast cancer. Despite these efforts, the establishment of conclusive evidence for such a role has been elusive. However, the development of extremely sophisticated new experimental techniques has allowed the recent development of evidence that human papilloma virus, Epstein-Barr virus, mouse mammary tumor virus and bovine leukemia virus may each have a role in the causation of human breast cancers. This is potentially good news as effective vaccines are already available to prevent infections from carcinogenic strains of human papilloma virus, which causes cancer of the uterine cervix.

  18. Estrogens and breast cancer

    Directory of Open Access Journals (Sweden)

    HANKINSON SUSAN E

    1997-01-01

    Full Text Available In this review, we summarize the epidemiologic evidence for the associations of oral contraceptives and postmenopausal hormones with risk of breast cancer. We also describe the biologic plausibility of these relationships. Overall, there appears to be little, if any, increase in risk with oral contraceptive use in general, even among users for 10 or more years. However, compared to never users, current oral contraceptive users appear to have a modest elevation in risk that subsides within about 10 years after cessation of use. For postmenopausal hormones, the weight of the evidence suggests little or no increase in risk among users of short duration, or for use in the past. However, current longer term use is associated with an increased risk of breast cancer that increases with duration. This increase in risk is large enough, and well enough supported, to be considered along with the other risks and benefits of postmenopausal hormone therapy.

  19. Imaging inflammatory breast cancer.

    Science.gov (United States)

    Alunni, J-P

    2012-02-01

    Carcinomatous mastitis is a severe form of breast cancer and its diagnosis is essentially clinical and histological. The first examination to perform is still mammography, not only to provide evidence supporting this diagnosis but also to search for a primary intramammary lesion and assess local/regional spread. It is essential to study the contralateral breast for bilaterality. Ultrasound also provides evidence supporting inflammation, but appears to be better for detecting masses and analysing lymph node areas. The role of MRI is debatable, both from a diagnostic point of view and for monitoring during treatment, and should be reserved for selected cases. An optimal, initial radiological assessment will enable the patient to be monitored during neoadjuvant chemotherapy. Copyright © 2011 Éditions française de radiologie. Published by Elsevier Masson SAS. All rights reserved.

  20. Heterogeneity in breast cancer.

    Science.gov (United States)

    Polyak, Kornelia

    2011-10-01

    Breast cancer is a heterogeneous disease. There is a high degree of diversity between and within tumors as well as among cancer-bearing individuals, and all of these factors together determine the risk of disease progression and therapeutic resistance. Advances in technologies such as whole-genome sequencing and functional viability screens now allow us to analyze tumors at unprecedented depths. However, translating this increasing knowledge into clinical practice remains a challenge in part due to tumor evolution driven by the diversity of cancer cell populations and their microenvironment. The articles in this Review series discuss recent advances in our understanding of breast tumor heterogeneity, therapies tailored based on this knowledge, and future ways of assessing and treating heterogeneous tumors.