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Sample records for breast cancer angiogenesis

  1. Soy and breast cancer: focus on angiogenesis.

    PubMed

    Varinska, Lenka; Gal, Peter; Mojzisova, Gabriela; Mirossay, Ladislav; Mojzis, Jan

    2015-05-22

    Epidemiological studies have revealed that high consumption of soy products is associated with low incidences of hormone-dependent cancers, including breast and prostate cancer. Soybeans contain large amounts of isoflavones, such as the genistein and daidzain. Previously, it has been demonstrated that genistein, one of the predominant soy isoflavones, can inhibit several steps involved in carcinogenesis. It is suggested that genistein possesses pleiotropic molecular mechanisms of action including inhibition of tyrosine kinases, DNA topoisomerase II, 5α-reductase, galectin-induced G2/M arrest, protein histidine kinase, and cyclin-dependent kinases, modulation of different signaling pathways associated with the growth of cancer cells (e.g., NF-κB, Akt, MAPK), etc. Moreover, genistein is also a potent inhibitor of angiogenesis. Uncontrolled angiogenesis is considered as a key step in cancer growth, invasion, and metastasis. Genistein was found to inhibit angiogenesis through regulation of multiple pathways, such as regulation of VEGF, MMPs, EGFR expressions and NF-κB, PI3-K/Akt, ERK1/2 signaling pathways, thereby causing strong antiangiogenic effects. This review focuses on the antiangiogenic properties of soy isoflavonoids and examines their possible underlying mechanisms.

  2. Targeting Angiogenesis in Metastatic Breast Cancer

    PubMed Central

    Reddy, Sangeetha; Raffin, Michael

    2012-01-01

    Angiogenesis has become an important target in the treatment of several solid tumors, including breast cancer. As monotherapy, antiangiogenic agents have demonstrated limited activity in metastatic breast cancer (MBC); therefore, they have generally been developed for use in combination with chemotherapies. Thus far, the experience with antiangiogenic agents for MBC has been mixed. The results from one study assessing addition of the monoclonal antibody bevacizumab to paclitaxel led to approval of bevacizumab for MBC. However, the modest improvement of progression-free survival rates in subsequent MBC studies has led to reappraisal of bevacizumab. Phase III studies have not produced evidence supporting use of the multikinase inhibitor sunitinib alone or in combination with MBC chemotherapy. Experience with sorafenib in a phase IIb program indicates potential when used in select combinations, particularly with capecitabine; however, phase III confirmatory data are needed. Although antiangiogenic therapies combined with chemotherapy have increased progression-free survival rates for patients with MBC, increases in overall survival times have not been observed. Some studies have tried to combine antiangiogenic agents such as bevacizumab and sunitinib or sorafenib, but that approach has been limited because of toxicity concerns. Sequential use of antiangiogenic agents with differing mechanisms of action may be an effective approach. Despite setbacks, angiogenesis will likely remain an important target of treatment for selected patients with MBC. PMID:22843553

  3. Anti-Angiogenesis Therapeutic Indicators in Breast Cancer

    DTIC Science & Technology

    2004-08-01

    Knopp, M. V., Brix , G.. Junkermann, H. J., Sinn. H. P. MR mam- ing angiogenesis using macromolecular contrast media: Status mography with pharmacokinetic...Essig, M., Debus, J., Knopp, M. V.. Engenhart- primary breast cancer to neo-adjuvant chemotherapy. Eur. Radiol. Cabilic, R.. Schonberg, S. 0., Brix ...Engenhart, R.. Knopp, M. V., Brix , G., Grandy, M.. 16. Torts, P. S., Brix , G.. Buckley, D. L., Evelhoch, J. L., Henderson, E., Essig, M., Miltner, P

  4. Characterization of the Role of Heyl in Angiogenesis and Breast Cancer Development

    DTIC Science & Technology

    2005-03-01

    AD Award Number: W81XWH-04- 1 -0382 TITLE: Characterization of the Role of Heyl in Angiogenesis and Breast Cancer Development PRINCIPAL INVESTIGATOR...Characterization of the Role of Heyl in Angiogenesis and W81XWH-04- 1 -0382 Breast Cancer Development 6. A UTHOR(S) Liangfeng Han, M.D. 7. PERFORMING...11 Body 1 . Investigate the angiogenesis role of HEYL in breast cancer in vitro A: Generate adenovirus expressing I IEYL (ref. 1 )and anti-I JEYL

  5. Digital Microscopy Assessment of Angiogenesis in Different Breast Cancer Compartments

    PubMed Central

    Rogojanu, Radu; Croitoru, Camelia; Jitaru, Daniela; Tarniceriu, Cristina; Carasevici, Eugen

    2013-01-01

    Background/Aim. Tumour angiogenesis defined by microvessel density (MVD) is generally accepted as a prognostic factor in breast cancer. However, due to variability of measurement systems and cutoffs, it is questionable to date whether it contributes to predictive outline. Our study aims to grade vascular heterogeneity by comparing clear-cut compartments: tumour associated stroma (TAS), tumour parenchyma, and tumour invasive front. Material and Methods. Computerized vessel area measurement was performed using a tissue cytometry system (TissueFAXS) on slides originated from 50 patients with breast cancer. Vessels were marked using immunohistochemistry with CD34. Regions of interest were manually defined for each tumour compartment. Results. Tumour invasive front vascular endothelia area was 2.15 times higher than that in tumour parenchyma and 4.61 times higher than that in TAS (P < 0.002). Worth to mention that the lymph node negative subgroup of patients show a slight but constant increase of vessel index in all examined compartments of breast tumour. Conclusion. Whole slide digital examination and region of interest (ROI) analysis are a valuable tool in scoring angiogenesis markers and disclosing their prognostic capacity. Our study reveals compartments' variability of vessel density inside the tumour and highlights the propensity of invasive front to associate an active process of angiogenesis with potential implications in adjuvant therapy. PMID:24073397

  6. Regulation of angiogenesis via Notch signaling in breast cancer and cancer stem cells.

    PubMed

    Zhou, Weiqiang; Wang, Guangdi; Guo, Shanchun

    2013-12-01

    Breast cancer angiogenesis is elicited and regulated by a number of factors including the Notch signaling. Notch receptors and ligands are expressed in breast cancer cells as well as in the stromal compartment and have been implicated in carcinogenesis. Signals exchanged between neighboring cells through the Notch pathway can amplify and consolidate molecular differences, which eventually dictate cell fates. Notch signaling and its crosstalk with many signaling pathways play an important role in breast cancer cell growth, migration, invasion, metastasis and angiogenesis, as well as cancer stem cell (CSC) self-renewal. Therefore, significant attention has been paid in recent years toward the development of clinically useful antagonists of Notch signaling. Better understanding of the structure, function and regulation of Notch intracellular signaling pathways, as well as its complex crosstalk with other oncogenic signals in breast cancer cells will be essential to ensure rational design and application of new combinatory therapeutic strategies. Novel opportunities have emerged from the discovery of Notch crosstalk with inflammatory and angiogenic cytokines and their links to CSCs. Combinatory treatments with drugs designed to prevent Notch oncogenic signal crosstalk may be advantageous over λ secretase inhibitors (GSIs) alone. In this review, we focus on the more recent advancements in our knowledge of aberrant Notch signaling contributing to breast cancer angiogenesis, as well as its crosstalk with other factors contributing to angiogenesis and CSCs.

  7. Endothelial Robo4 suppresses breast cancer growth and metastasis through regulation of tumor angiogenesis.

    PubMed

    Zhao, Helong; Ahirwar, Dinesh K; Oghumu, Steve; Wilkie, Tasha; Powell, Catherine A; Nasser, Mohd W; Satoskar, Abhay R; Li, Dean Y; Ganju, Ramesh K

    2016-02-01

    Targeting tumor angiogenesis is a promising alternative strategy for improvement of breast cancer therapy. Robo4 (roundabout homolog 4) signaling has been shown to protect endothelial integrity during sepsis shock and arthritis, and inhibit Vascular Endothelial Growth Factor (VEGF) signaling during pathological angiogenesis of retinopathy, which indicates that Robo4 might be a potential target for angiogenesis in breast cancer. In this study, we used immune competent Robo4 knockout mouse model to show that endothelial Robo4 is important for suppressing breast cancer growth and metastasis. And this effect does not involve the function of Robo4 on hematopoietic stem cells. Robo4 inhibits breast cancer growth and metastasis by regulating tumor angiogenesis, endothelial leakage and tight junction protein zonula occludens protein-1 (ZO-1) downregulation. Treatment with SecinH3, a small molecule drug which deactivates ARF6 downstream of Robo4, can enhance Robo4 signaling and thus inhibit breast cancer growth and metastasis. SecinH3 mediated its effect by reducing tumor angiogenesis rather than directly affecting cancer cell proliferation. In conclusion, endothelial Robo4 signaling is important for suppressing breast cancer growth and metastasis, and it can be targeted (enhanced) by administrating a small molecular drug.

  8. The oncoprotein HBXIP enhances angiogenesis and growth of breast cancer through modulating FGF8 and VEGF.

    PubMed

    Liu, Fabao; You, Xiaona; Wang, Yue; Liu, Qian; Liu, Yunxia; Zhang, Shuqin; Chen, Lingyi; Zhang, Xiaodong; Ye, Lihong

    2014-05-01

    Tumor angiogenesis plays an important role in the development of cancer. Previously, we reported that hepatitis B X-interacting protein (HBXIP) functioned as an oncoprotein in breast cancer. However, the role of HBXIP in angiogenesis in breast cancer remains poorly understood. In the present study, we show that the oncoprotein HBXIP plays crucial roles in the event. We observed that the expression levels of HBXIP were positively correlated with those of fibroblast growth factor 8 (FGF8) or vascular endothelial growth factor (VEGF) in clinical breast cancer tissues. Then, we demonstrated that HBXIP was able to upregulate FGF8 through activation of its promoter involving direct binding to cAMP response element-binding protein (CREB) in breast cancer cells and thereby increased its secretion. Strikingly, we identified another pathway that HBXIP upregulated FGF8 and VEGF through inhibiting miRNA-503, which directly targeted 3' untranslated region of FGF8 or VEGF mRNA in the cells. Moreover, we revealed that HBXIP-induced FGF8 could upregulate VEGF expression through activating phosphoinositide 3-kinase (PI3K)/Akt/hypoxia-inducible factor 1-alpha (HIF1α) signaling and increase its secretion. In function, matrigel angiogenesis assay and hemoglobin content analysis uncovered that HBXIP-enhanced FGF8/VEGF boosted tumor angiogenesis and growth in breast cancer in vitro and in vivo in a paracrine/autocrine manner. Thus, we conclude that HBXIP enhances angiogenesis and growth of breast cancer through modulating FGF8 and VEGF. Our finding provides new insights into the mechanism of tumor angiogenesis in breast cancer. Therapeutically, HBXIP may serve as a novel target of tumor angiogenesis.

  9. Modulation of angiogenesis by dietary phytoconstituents in the prevention and intervention of breast cancer.

    PubMed

    Reuben, Sharon C; Gopalan, Ashwin; Petit, Danielle M; Bishayee, Anupam

    2012-01-01

    Breast cancer is the leading cause of cancer-related deaths for women in the United States and the rest of the world. About 8% of women develop breast cancer during the course of their lives. Dietary habits are closely associated with both the risk and progression of breast cancer. Dietary agents have accumulated increasing importance with regards to the prevention and treatment of breast cancer. One such manner by which these compounds can target breast cancer development and progression is through interference with the angiogenic pathways. Angiogenesis is an intricate process that involves the development of new capillaries from previously existing blood vessels. Disruption of this pathway, therefore, provides a novel and effective avenue for therapeutic intervention of breast cancer. Various phytochemicals found in the diet kill breast cancer cells in vitro and prevent as well as suppress breast cancer progression in various preclinical animal models. This review examines the value of dietary phytoconstituents in the prevention and treatment of breast cancer through modulation of the intricate and complex process of angiogenesis. In addition, the potential benefits, challenges, and future directions of research on anti-angiogenic dietary phytochemicals in the prevention and intervention of breast cancer are also addressed.

  10. Cleavage of galectin-3 by matrix metalloproteases induces angiogenesis in breast cancer

    PubMed Central

    Nangia-Makker, Pratima; Wang, Yi; Raz, Tirza; Tait, Larry; Balan, Vitaly; Hogan, Victor; Raz, Avraham

    2012-01-01

    Galectin-3 cleavage is related to progression of human breast and prostate cancer and is partly responsible for tumor growth, angiogenesis and apoptosis resistance in mouse models. A functional polymorphism in galectin-3 gene, determining its susceptibility to cleavage by matrix metalloproteinases (MMPs)-2/-9 is related to racial disparity in breast cancer incidence in Asian and Caucasian women. The purpose of our study is to evaluate (i) if cleavage of galectin-3 could be related to angiogenesis during the progression of human breast cancer, (ii) the role of cleaved galectin-3 in induction of angiogenesis and (iii) determination of the galectin-3 domain responsible for induction of angiogenic response. Galectin-3 null breast cancer cells BT-459 were transfected with either cleavable full-length galectin-3 or its fragmented peptides. Chemotaxis, chemoinvasion, heterotypic aggregation, epithelial-endothelial cell interactions and angiogenesis were compared to noncleavable galectin-3. BT-549-H64 cells harboring cleavable galectin-3 exhibited increased chemotaxis, invasion and interactions with endothelial cells resulting in angiogenesis and 3D morphogenesis compared to BT-549-P64 cells harboring noncleavable galectin-3. BT-549-H64 cells induced increased migration and phosphorylation of focal adhesion kinase in migrating endothelial cells. Endothelial cells cocultured with BT-549 cells transfected with galectin-3 peptides indicate that amino acids 1–62 and 33–250 stimulate migration and morphogenesis of endothelial cells. Immunohistochemical analysis of blood vessel density and galectin-3 cleavage in a breast cancer progression tissue array support the in vitro findings. We conclude that the cleavage of the N terminus of galectin-3 followed by its release in the tumor microenvironment in part leads to breast cancer angiogenesis and progression. PMID:20162566

  11. Cancer cell CCL5 mediates bone marrow independent angiogenesis in breast cancer

    PubMed Central

    Sax, Michael John; Gasch, Christin; Athota, Vineel Rag; Freeman, Ruth; Rasighaemi, Parisa; Westcott, David Elton; Day, Christopher John; Nikolic, Iva; Elsworth, Benjamin; Wei, Ming; Rogers, Kelly; Swarbrick, Alexander; Mittal, Vivek; Pouliot, Normand; Mellick, Albert Sleiman

    2016-01-01

    It has recently been suggested that the chemokine receptor (CCR5) is required for bone marrow (BM) derived endothelial progenitor cell (EPC) mediated angiogenesis. Here we show that suppression of either cancer cell produced CCL5, or host CCR5 leads to distinctive vascular and tumor growth defects in breast cancer. Surprisingly, CCR5 restoration in the BM alone was not sufficient to rescue the wild type phenotype, suggesting that impaired tumor growth associated with inhibiting CCL5/CCR5 is not due to defects in EPC biology. Instead, to promote angiogenesis cancer cell CCL5 may signal directly to endothelium in the tumor-stroma. In support of this hypothesis, we have also shown: (i) that endothelial cell CCR5 levels increases in response to tumor-conditioned media; (ii) that the amount of CCR5+ tumor vasculature correlates with invasive grade; and (iii) that inhibition of CCL5/CCR5 signaling impairs endothelial cell migration, associated with a decrease in activation of mTOR/AKT pathway members. Finally, we show that treatment with CCR5 antagonist results in less vasculature, impaired tumor growth, reduced metastases and improved survival. Taken as a whole, this work demonstrates that directly inhibiting CCR5 expressing vasculature constitutes a novel strategy for inhibiting angiogenesis and blocking metastatic progression in breast cancer. PMID:27863423

  12. CCL18 from tumor-associated macrophages promotes angiogenesis in breast cancer.

    PubMed

    Lin, Ling; Chen, Yong-Song; Yao, Yan-Dan; Chen, Jing-Qi; Chen, Jia-Ning; Huang, Song-Yin; Zeng, Yun-Jie; Yao, He-Rui; Zeng, Si-Hai; Fu, Yong-Shui; Song, Er-Wei

    2015-10-27

    The infiltration of tumor-associated macrophages (TAMs) is associated with extensive angiogenesis, which contributes to a poor prognosis in breast cancer. However, anti-angiogenic therapy with VEGF-specific monotherapy has been unsuccessful in treating breast cancer, and the molecular mechanisms associated with chemoresistance remain unclear. Here, we investigated whether CCL18, a chemokine produced by TAMs, can stimulate angiogenesis in breast cancer, as well as the underlying mechanisms. Double immunohistochemical staining for CCL18 and CD34/CD31/vWF was performed in 80 breast cancer samples to study the correlation between CCL18+ TAMs and microvascular density (MVD). Cocultures of TAMs with human umbilical vein endothelial cells (HUVECs) were used to model the inflammatory microenvironment, and CCL18-induced angiogenesis was evaluated both in vitro and in vivo. We demonstrated that CCL18+ TAM infiltration positively associated with MVD in breast cancer samples, which was correlated with tumor metastasis and poor prognosis. We confirmed, both in vitro and in vivo, that CCL18 and VEGF synergistically promoted endothelial cell migration and angiogenesis. Conversely, blocking CCL18 or VEGF with neutralizing antibodies synergistically inhibited the promigratory effects of TAMs. Silencing PITPNM3, a putative CCL18 receptor, on the surface of HUVECs abrogated CCL18-mediated promigration and the enhancement of HUVEC tube formation, independently of VEGFR signaling. Moreover, CCL18 exposure induced the endothelial-mesenchymal transformation and activated ERK and Akt/GSK-3β/Snail signaling in HUVECs, thereby contributing to its pro-angiogenic effects. In conclusion, our findings suggest that CCL18 released from TAMs promotes angiogenesis and tumor progression in breast cancer; thus, CCL18 may serve as a novel target for anti-angiogenic therapies.

  13. The anthraquinone derivative Emodin inhibits angiogenesis and metastasis through downregulating Runx2 activity in breast cancer.

    PubMed

    Ma, Junchao; Lu, Hong; Wang, Shan; Chen, Bin; Liu, Zhaojie; Ke, Xiaoqin; Liu, Ting; Fu, Jianjiang

    2015-04-01

    Emodin (EMD) is an anthraquinone derivative extracted from the root and rhizome of Rheum palmatum L. which exhibits a range of activities, including anti-bacterial, antitumor, diuretic and vasorelaxant effects. The ability to inhibit metastasis and angiogenesis was shown in previous pharmacological studies, but clear information to address EMD affecting angiogenesis and metastasis in human breast cancer is still lacking. In the present study, we evaluated a possible role for EMD in angiogenesis and metastasis induced by breast cancer cells. It was revealed here that EMD attenuated tumor cell-induced metastasis and angiogenesis both in vitro and in vivo. Furthermore, it was found that these inhibitory effects were caused by MMPs and VEGFR-2 inhibition in metastatic breast cancer cells and endothelial cells, respectively. Western blot analysis showed reduction of Runx2 activation in the EMD-treated cells. ELISA based Runx2 transcription factor assay showed that the interaction between Runx2 and target sequences was inhibited by EMD. Our findings suggested that the inhibitory effects of EMD on tumor-induced metastasis and angiogenesis were caused by MMPs and VEGFR-2 inhibition, which may be associated with the downregulation of Runx2 transcriptional activity.

  14. A Model for Breast Cancer-Induced Angiogenesis

    DTIC Science & Technology

    1996-09-01

    Terman BI, Carrion ME, Kovacs E, Rasmussen BA, Eddy RL, Shows TB. Identification of a new endothelial cell growth factor receptor tyrosine kinase...Jensen, H. M., Chen, I., DeVault, M. R., and Lewis , A. E. Angio- Cancer Res. Treat., 11: 241-248, 1988. genesis induced by "normal" human breast

  15. Sympathetic Nerves in Breast Cancer: Angiogenesis and Antiangiogenic Therapy

    DTIC Science & Technology

    2013-02-01

    treatment, we measured the NE metabolite normetanephrine (NMN). The production of NMN from NE is catalyzed by catechol-o-methyl transferase ( COMT ...Liverpool, E.B. Brown. 2011. Department of Defense Breast Cancer Research Program Era of Hope Conference. Orlando, FL, August 2-5, 2011. DETECTION

  16. TRPS1 expression promotes angiogenesis and affects VEGFA expression in breast cancer.

    PubMed

    Hu, Jing; Su, Peng; Jia, Ming; Wu, Xiaojuan; Zhang, Hui; Li, Weiwei; Zhou, Gengyin

    2014-04-01

    Angiogenesis is a hallmark of the malignant process in breast cancer in which vascular endothelial growth factor A (VEGFA) plays an important role. Trichorhinophalangeal syndrome type 1 (TRPS1) is a GATA-type transcription factor and is involved in trichorhinophalangeal syndrome type 1. To investigate the role of TRPS1 in breast cancer angiogenesis, we analyzed the expression of TRPS1 and microvessel density (MVD) marker CD31 by immunohistochemistry in 117 paraffin-embedded breast tissues. TRPS1 expression was positively correlated with CD31. We further investigated whether TRPS1 induces human umbilical vein endothelial cell (HUVEC) migration and VEGFA expression of breast cancer cells. The over-expression of TRPS1 induced a significant increase in HUVEC migration accompanied by VEGFA up-regulation in transfected cells. In contrast, knockdown of TRPS1 decreased the induction of HUVEC migration and significantly down-regulated VEGFA expression. Furthermore, endogenous TRPS1 was present in the VEGFA promoter, as determined by chromatin immunoprecipitation assay. Taken together, this study showed that TRPS1 promotes angiogenesis and affects VEGFA expression in breast cancer.

  17. Clinicopathological significance of NGX6 expression in breast cancer and its relationship to angiogenesis.

    PubMed

    Xiao, Jidong; Mao, Yuyao; Zhou, Yuanquan; Xiang, Kaimin

    2015-01-01

    The aim was to explore clinicopathological significance of Nasopharyngeal carcinoma-associated gene 6 (NGX6) expression in breast cancer and its relationship to angiogenesis. Clinicopathological feature of 168 patients with breast cancer were analyzed. NGX6 expression and microvessel density (MVD) in tumor tissue were measured using immunohistochemistry methods. The association of NGX6 expression with MVD and clinicopathological features was assessed. Among 168 cases of breast cancer, NGX6 positive expression were found in 92 (54.8%) cases and NGX6 negative expression were found in 76 (45.2%) cases. Incidence rate of large size tumor, high tumor node metastasis (TNM) stage and lymph node metastasis in NGX6 negative expression group were higher than NGX6 positive expression group in breast cancer (P=0.003, 0.007, and 0.003, respectively). MVD in NGX6 negative expression group is 22.5±4.8, MVD in NGX6 positive expression group is 15.2±4.2. MVD in the NGX6 negative expression group was significantly higher than the NGX6 positive expression group (P<0.05). The expression of NGX6 was closely associated with tumor size, TNM stage, lymph node metastasis and MVD. NGX6 is involved in metastasis and angiogenesis activity of breast cancer. The study may provide a theoretical basis for anti-angiogenic therapy of breast cancer.

  18. miR-195 inhibits tumor growth and angiogenesis through modulating IRS1 in breast cancer.

    PubMed

    Wang, Yilin; Zhang, Xiaolong; Zou, Chao; Kung, Hsiang-Fu; Lin, Marie C; Dress, Andreas; Wardle, Fiona; Jiang, Bing-Hua; Lai, Lihui

    2016-05-01

    Angiogenesis has been found as an attractive target for drug therapy as it is necessary for tumor growth. Accumulating evidences show that microRNAs (miRNAs), which are a group of highly conserved, single-stranded, short non-coding RNAs, play important roles through directly targeting angiogenic factors and protein kinases. The purpose of this study is to investigate the role of miR-195 in breast cancer development and angiogenesis through targeting IRS1. We show that miR-195 is inversely related with Insulin receptor substrate 1 (IRS1) in both breast cancer cells and breast cancer tissues. Induction of miR-195 could suppress IRS1 protein expression through binding to its 3'UTR regions either by transfection with miR-195 oligo or by infection with lentivirus encoding miR-195 gene. Moreover, re-expression of IRS1 reverses miR-195-mediated repression of tumor cell growth and miR-195 inhibits tumor angiogenesis through suppressing IRS1-VEGF axis. These data suggest that miR-195 mimics are potential therapeutic agents for breast cancer diagnose.

  19. Obesity promotes breast cancer by CCL2-mediated macrophage recruitment and angiogenesis.

    PubMed

    Arendt, Lisa M; McCready, Jessica; Keller, Patricia J; Baker, Dana D; Naber, Stephen P; Seewaldt, Victoria; Kuperwasser, Charlotte

    2013-10-01

    Obesity is one of the most important preventable causes of cancer and the most significant risk factor for breast cancer in postmenopausal women. Compared with lean women, obese women are more likely to be diagnosed with a larger, higher grade tumor, an increased incidence of lymph node metastases, and elevated risk of distant recurrence. However, the mechanisms connecting obesity to the pathogenesis of breast cancer are poorly defined. Here, we show that during obesity, adipocytes within human and mouse breast tissues recruit and activate macrophages through a previously uncharacterized CCL2/IL-1β/CXCL12 signaling pathway. Activated macrophages in turn promote stromal vascularization and angiogenesis even before the formation of cancer. Recapitulating these changes using a novel humanized breast cancer model was sufficient to promote angiogenesis and prime the microenvironment prior to neoplastic transformation for accelerated breast oncogenesis. These findings provide a mechanistic role for adipocytes and macrophages before carcinogenesis that may be critical for prevention and treatment of obesity-related cancer. ©2013 AACR.

  20. Pseudogene CYP4Z2P 3′UTR promotes angiogenesis in breast cancer

    SciTech Connect

    Zheng, Lufeng; Li, Xiaoman; Gu, Yi; Ma, Yihua; Xi, Tao

    2014-10-24

    Highlights: • A new critical role of pseudogene CYP4Z2P 3′UTR in breast cancer is proposed. • We examine the level of pseudogene CYP4Z2P 3′UTR in breast cancer tissues. • The functions of CYP4Z2P 3′UTR and mechanism were studied. • The mechanism provides new insights for the breast cancer progression. - Abstract: Pseudogenes have long been marked as “false” genes, which are similar with real genes but have no apparent function. The 3′UTR is well-known to regulate gene expression post-transcriptionally. Our recent evidence, however, indicates novel functional roles of pseudogene CYP4Z2P 3′UTR (Z2P-UTR). We found that ectopic expression of Z2P-UTR in breast cancer cells significantly increased the expression of VEGF-A without affecting cell proliferation in vitro. Meanwhile, conditioned medium (CM) from Z2P-UTR overexpression cells enhanced proliferation, migration and tube formation of HUVEC, and promoted angiogenesis in ex vivo models. Also, CM increased the expression of VEGFR2 in HUVEC. Our data suggest that Z2P-UTR can promote breast cancer angiogenesis partly via paracrine pathway of VEGF-A/VEGFR2.

  1. Effect of Melatonin on Tumor Growth and Angiogenesis in Xenograft Model of Breast Cancer

    PubMed Central

    Jardim-Perassi, Bruna Victorasso; Arbab, Ali S.; Ferreira, Lívia Carvalho; Borin, Thaiz Ferraz; Varma, Nadimpalli R. S.; Iskander, A. S. M.; Shankar, Adarsh; Ali, Meser M.; de Campos Zuccari, Debora Aparecida Pires

    2014-01-01

    As neovascularization is essential for tumor growth and metastasis, controlling angiogenesis is a promising tactic in limiting cancer progression. Melatonin has been studied for their inhibitory properties on angiogenesis in cancer. We performed an in vivo study to evaluate the effects of melatonin treatment on angiogenesis in breast cancer. Cell viability was measured by MTT assay after melatonin treatment in triple-negative breast cancer cells (MDA-MB-231). After, cells were implanted in athymic nude mice and treated with melatonin or vehicle daily, administered intraperitoneally 1 hour before turning the room light off. Volume of the tumors was measured weekly with a digital caliper and at the end of treatments animals underwent single photon emission computed tomography (SPECT) with Technetium-99m tagged vascular endothelial growth factor (VEGF) C to detect in vivo angiogenesis. In addition, expression of pro-angiogenic/growth factors in the tumor extracts was evaluated by membrane antibody array and collected tumor tissues were analyzed with histochemical staining. Melatonin in vitro treatment (1 mM) decreased cell viability (p<0.05). The breast cancer xenografts nude mice treated with melatonin showed reduced tumor size and cell proliferation (Ki-67) compared to control animals after 21 days of treatment (p<0.05). Expression of VEGF receptor 2 decreased significantly in the treated animals compared to that of control when determined by immunohistochemistry (p<0.05) but the changes were not significant on SPECT (p>0.05) images. In addition, there was a decrease of micro-vessel density (Von Willebrand Factor) in melatonin treated mice (p<0.05). However, semiquantitative densitometry analysis of membrane array indicated increased expression of epidermal growth factor receptor and insulin-like growth factor 1 in treated tumors compared to vehicle treated tumors (p<0.05). In conclusion, melatonin treatment showed effectiveness in reducing tumor growth and cell

  2. Kindlin-3 enhances breast cancer progression and metastasis by activating Twist-mediated angiogenesis

    PubMed Central

    Sossey-Alaoui, Khalid; Pluskota, Elzbieta; Davuluri, Gangarao; Bialkowska, Katarzyna; Das, Mitali; Szpak, Dorota; Lindner, Daniel J.; Downs-Kelly, Erinn; Thompson, Cheryl L.; Plow, Edward F.

    2014-01-01

    The FERM domain containing protein Kindlin-3 has been recognized as a major regulator of integrin function in hematopoietic cells, but its role in neoplasia is totally unknown. We have examined the relationship between Kindlin-3 and breast cancer in mouse models and human tissues. Human breast tumors showed a ∼7-fold elevation in Kindlin-3 mRNA compared with nonneoplastic tissue by quantitative polymerase chain reaction. Kindlin-3 overexpression in a breast cancer cell line increased primary tumor growth and lung metastasis by 2.5- and 3-fold, respectively, when implanted into mice compared with cells expressing vector alone. Mechanistically, the Kindlin-3-overexpressing cells displayed a 2.2-fold increase in vascular endothelial growth factor (VEGF) secretion and enhanced β1 integrin activation. Increased VEGF secretion resulted from enhanced production of Twist, a transcription factor that promotes tumor angiogenesis. Knockdown of Twist diminished VEGF production, and knockdown of β1 integrins diminished Twist and VEGF production by Kindlin-3-overexpressing cells, while nontargeting small interfering RNA had no effect on expression of these gene products. Thus, Kindlin-3 influences breast cancer progression by influencing the crosstalk between β1 integrins and Twist to increase VEGF production. This signaling cascade enhances breast cancer cell invasion and tumor angiogenesis and metastasis.—Sossey-Alaoui, K., Pluskota, E., Davuluri, G., Bialkowska, K., Das, M., Szpak, D., Lindner, D. J., Downs-Kelly, E., Thompson, C. L., Plow, E. F. Kindlin-3 enhances breast cancer progression and metastasis by activating Twist-mediated angiogenesis. PMID:24469992

  3. The role of semaphorin 4D in tumor development and angiogenesis in human breast cancer

    PubMed Central

    Jiang, Hongchao; Chen, Ceshi; Sun, Qiangming; Wu, Jing; Qiu, Lijuan; Gao, Change; Liu, Weiqing; Yang, Jun; Jun, Nie; Dong, Jian

    2016-01-01

    Background Semaphorin 4D (Sema4D) is highly expressed in certain types of tumors and functions in the regulation of tumor angiogenesis and growth. However, it is still not clear regarding the roles of Sema4D in breast cancer. This study was designed to explore the effects of Sema4D on proliferation, cell cycle progression, apoptosis, invasion, migration, tumor growth, and angiogenesis in breast cancer. Materials and methods The expression level of Sema4D was investigated in MCF10A, 184A1, HCC1937, MDA-MB-468, MDA-MB-231, Hs578T, BT474, MCF-7, and T47D breast cancer cell lines by Western blotting analysis. Sema4D downregulation or overexpression was established by infection with lentiviruses-encoding Sema4D short hairpin RNA (shRNA) or Sema4D. To evaluate the effects of Sema4D on cell proliferation, cell cycle progression, apoptosis, invasion, and migration of MDA-MB-231 and MDA-MB-468 cells, methods including MTT assay, flow cytometry, wound healing assay, and transwell experiments were applied. BALB/c nude mice were injected with MDA-MB-231 cells, which were respectively infected with lentiviruses-encoding Sema4D, Sema4D shRNA, and GFP, followed by tumor angiogenesis assay. Results Sema4D was expressed at higher levels in breast cancer cell lines compared with the normal human breast epithelial cell lines, especially in MDA-MB-231 and MDA-MB-468 cells. Cell proliferation ability was remarkably inhibited in Sema4D downregulated condition, whereas the proportions of cells in the G0/G1 phase and apoptosis increased in MDA-MB-231 and MDA-MB-468 cells. In addition, the invasion and migration abilities of these cells were obviously reduced. Xenograft growth as well as angiogenesis was inhibited when infected with lentiviruses-encoding Sema4D shRNA in vivo. Conclusion Downregulation of Sema4D had notable influence on cell proliferation ability, invasion, migration, and apoptosis of both MDA-MB-231 and MDA-MB-468 cells. Furthermore, infection with lentiviruses

  4. Increased expression of CYP4Z1 promotes tumor angiogenesis and growth in human breast cancer

    SciTech Connect

    Yu, Wei; Chai, Hongyan; Li, Ying; Zhao, Haixia; Xie, Xianfei; Zheng, Hao; Wang, Chenlong; Wang, Xue; Yang, Guifang; Cai, Xiaojun; Falck, John R.; Yang, Jing

    2012-10-01

    Cytochrome P450 (CYP) 4Z1, a novel CYP4 family member, is over-expressed in human mammary carcinoma and associated with high-grade tumors and poor prognosis. However, the precise role of CYP4Z1 in tumor progression is unknown. Here, we demonstrate that CYP4Z1 overexpression promotes tumor angiogenesis and growth in breast cancer. Stable expression of CYP4Z1 in T47D and BT-474 human breast cancer cells significantly increased mRNA expression and production of vascular endothelial growth factor (VEGF)-A, and decreased mRNA levels and secretion of tissue inhibitor of metalloproteinase-2 (TIMP-2), without affecting cell proliferation and anchorage-independent cell growth in vitro. Notably, the conditioned medium from CYP4Z1-expressing cells enhanced proliferation, migration and tube formation of human umbilical vein endothelial cells, and promoted angiogenesis in the zebrafish embryo and chorioallantoic membrane of the chick embryo. In addition, there were lower levels of myristic acid and lauric acid, and higher contents of 20-hydroxyeicosatetraenoic acid (20-HETE) in CYP4Z1-expressing T47D cells compared with vector control. CYP4Z1 overexpression significantly increased tumor weight and microvessel density by 2.6-fold and 1.9-fold in human tumor xenograft models, respectively. Moreover, CYP4Z1 transfection increased the phosphorylation of ERK1/2 and PI3K/Akt, while PI3K or ERK inhibitors and siRNA silencing reversed CYP4Z1-mediated changes in VEGF-A and TIMP-2 expression. Conversely, HET0016, an inhibitor of the CYP4 family, potently inhibited the tumor-induced angiogenesis with associated changes in the intracellular levels of myristic acid, lauric acid and 20-HETE. Collectively, these data suggest that increased CYP4Z1 expression promotes tumor angiogenesis and growth in breast cancer partly via PI3K/Akt and ERK1/2 activation. -- Highlights: ► CYP4Z1 overexpression promotes human breast cancer growth and angiogenesis. ► The pro-angiogenic effects of CYP4Z1 have

  5. Wogonoside inhibits angiogenesis in breast cancer via suppressing Wnt/β-catenin pathway.

    PubMed

    Huang, Yujie; Zhao, Kai; Hu, Yang; Zhou, Yuxin; Luo, Xuwei; Li, Xiaorui; Wei, Libin; Li, Zhiyu; You, Qidong; Guo, Qinglong; Lu, Na

    2016-11-01

    Wogonoside, a main flavonoid component derived from the root of Scutellaria baicalensis Georgi, has been reported to have anti-angiogenesis and anti-leukemia activities. However, whether it can inhibit tumor angiogenesis is unclear. In this study, we investigate the inhibitory effect of wogonoside on angiogenesis in breast cancer and its underlying mechanisms. ELISA assay shows that wogonoside (25, 50, and 100 µM) decreases the secretion of VEGF in MCF-7 cells by 30.0%, 35.4%, and 40.1%, respectively. We find it inhibits angiogenesis induced by the conditioned media from MCF-7 cells in vitro and in vivo by migration, tube formation, rat aortic ring, and chicken chorioallantoic membrane (CAM) assay. Meanwhile, wogonoside can inhibit the growth and angiogenesis of MCF-7 cells xenografts in nude mice. The reduction of tumor weight can be found both in wogonoside (80 mg/kg) and bevacizumab (20 mg/kg) treated group, and the tumor inhibition rate is 42.1% and 48.7%, respectively. In addition, mechanistic studies demonstrate that wogonoside suppresses the activation of Wnt/β-catenin pathway in MCF-7 cells. Wogonoside (100 µM) decreases the intracellular level of Wnt3a, increases the expression of GSK-3β, AXIN, and promotes the phosphorylation of β-catenin for proteasome degradation significantly. Furthermore, the nuclear accumulation of β-catenin and the DNA-binding activity of β-catenin/TCF/Lef complex are inhibited by 49.2% and 28.7%, respectively, when treated with 100 µM wogonoside. Taken together, our findings demonstrate that wogonoside is a potential inhibitor of tumor angiogenesis and can be developed as a therapeutic agent for breast cancer. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  6. Protective Effect of Perindopril on Tumor Progression and Angiogenesis in Animal Model of Breast Cancer.

    PubMed

    Patel, Snehal S; Nakka, Surender

    2017-01-01

    Studies have shown that the renin angiotensin system via angiogenesis is involved in tumor development. Therefore, objective of the present study was to examine the effect of perindopril on tumor growth and angiogenesis in animal models of breast cancer. In the present study, the effect of perindopril on tumor development of mammary gland cancer induced by 7,12-dimethylbenz[a]anthracene, mouse tumor xenograft and corneal micropocket model has been investigated. Anti-angiogenic effect by chick yolk sac membrane assay has also been studied. In the present study, it has been found that perindopril produced a significant inhibition of tumor growth, in DMBA induced breast cancer. Treatment also produced significant suppression of cancer biomarkers such as lactate dehydrogenase, gamma glutamyl transferase and inflammatory markers such as C-reactive protein, erythrocyte sedimentation rate. Histopathological analysis also showed that perindopril was able to inhibit tumor development by the inhibition of hyperplastic lesions. Perindopril produced significant inhibition of tumor growth, in a mouse xenograft model and caused inhibition of neovascularization in the corneal micropocket model. In chick yolk sac membrane assay, perindopril showed inhibition of vascular growth and reduced blood vessel formation. Therefore, perindopril is widely used in clinical practice, may represent a neo-adjuvant therapy for treatment of breast cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Quercetin inhibits angiogenesis by targeting calcineurin in the xenograft model of human breast cancer.

    PubMed

    Zhao, Xin; Wang, Qiuting; Yang, Shijun; Chen, Chen; Li, Xiaoya; Liu, Jinyu; Zou, Zhongmei; Cai, Dayong

    2016-06-15

    Vascular endothelial growth factor receptor 2 (VEGFR2) mediated calcineurin/nuclear factor of activated T-cells (NFAT) pathway is crucial in the angiogenesis of human breast cancer. Quercetin (Qu), a flavonoid known to possess anti-angiogenesis and antitumor properties, inhibited calcineurin activity in vitro. Herein, we performed a study in vivo to evaluate the effects of Qu on the angiogenesis in breast cancer. Female BALB/c nude mice were injected with MCF-7 cells into the mammary fat and were randomly divided into four groups. The animals were treated with vehicle solution, tamoxifen (TAM, 5.6mg/kg), tacrolimus (FK506, 3mg/kg), or Qu (34mg/kg) for 21 days, respectively. The results showed that, similar to TAM and FK506, Qu decreased tumor growth, limited oncocyte proliferation and promoted tumor necrosis. Anti-angiogenic actions of Qu were demonstrated as decreased serum VEGF (P<0.01), and sparse microvessel density (P<0.05). Qu significantly inhibited tumor calcineurin activities, and the inhibitory rate was 62.73% in Qu treated animals, compared to that was 72.90% in FK506 group (P>0.05). Effects of Qu on calcineurin/NFAT pathway were confirmed as decreased subcellular located levels of VEGF (P<0.05), VEGFR2 (P<0.05) and NFATc3 (P<0.01), downregulated gene expression of VEGF (P<0.05), VEGFR2 (P<0.05) and NFATc3 (P<0.01), reduced protein levels of VEGF (P<0.05), VEGFR2 (P<0.05), and NFATc3 (P<0.01) in tumor tissues. These findings indicate that Qu inhibit angiogenesis of human breast cancer xenograft in nude mice, which was associated with suppressing calcineurin activity and its regulated pathway activation.

  8. The novel VEGF receptor 2 inhibitor YLL545 inhibits angiogenesis and growth in breast cancer

    PubMed Central

    Zhang, Jianbo; Liu, Chen; Shi, Wen; Yang, Lingling; Zhang, Quansheng; Cui, Jianlin; Fang, Yangwu; Li, Yuhao; Ren, Guosheng; Yang, Shuang; Xiang, Rong

    2016-01-01

    Their antiangiogenic effects make vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors useful for cancer treatment. However, most of these drugs have unexpected adverse side effects. Here, we show that the novel VEGFR2 inhibitor YLL545 suppressed tumor angiogenesis and growth in triple-negative breast cancer without adverse effects. YLL545 treatment also markedly inhibited proliferation, migration, invasion, and tube formation by human umbilical vascular endothelial cells (HUVECs) in vitro. These effects of YLL545 were equal to or greater than those seen with sorafenib. In addition, YLL545 inhibited VEGF-induced phosphorylation of VEGFR2 and activation of downstream signaling regulators, such as phospho-STAT3 and phospho-ERK1/2, in HUVECs. Embryonic angiogenesis assays in zebrafish and Matrigel plug assays in mice demonstrated that YLL545 inhibits angiogenesis in vivo. YLL545 also inhibited proliferation and induced apoptosis in MDA-MB-231 breast cancer cells both in vitro and in vivo, and 50 mg/kg/d YLL545 inhibited human tumor xenograft growth by more than 50% in BALB/c nude mice. These observations suggest YLL545 is a potentially useful anticancer drug candidate. PMID:27203384

  9. Lysine demethylase 2A promotes stemness and angiogenesis of breast cancer by upregulating Jagged1

    PubMed Central

    Chen, Jing-Yi; Li, Chien-Feng; Chu, Pei-Yi; Lai, You-Syuan; Chen, Chung-Hsing; Jiang, Shih Sheng; Hou, Ming-Feng; Hung, Wen-Chun

    2016-01-01

    Alterations of histone methylation dynamically regulated by methyltransferases and demethylases are frequently found in human cancers. Here, we showed that expression of lysine demethylase 2A (KDM2A) is markedly increased in human breast cancer and its overexpression is associated with tumor progression and poor prognosis. Knockdown of KDM2A in breast cancer cells reduced proliferation but not viability. Gene set enrichment analysis revealed that inhibition of KDM2A down-regulates angiogenic genes with concurrent reduction of Jagged1 (JAG1), NOTCH1 and HEY1 in the NOTCH signaling. Chromatin immunoprecipitation- quantitative polymerase chain reaction (ChIP-qPCR) demonstrated the binding of KDM2A to the JAG1 promoter and the increase of methylation of Lys-36 of histone H3 (H3K36) in KDM2A-depleted MDA-MB-231 cells. Tumorsphere formation was significantly reduced in KDM2A-depleted cells which could be reversed by ectopic expression of JAG1. A selective KDM2A inhibitor daminozide also decreased the number of tumorsphere and the number of CD24−/CD44hi cells. In addition, daminozide acted synergistically with cisplatin in cell killing. We identified SOX2 as a direct transcriptional target of KDM2A to promote cancer stemness. Depletion of KDM2A in MDA-MB-231 cells attenuated NOTCH activation and tube formation in co-cultured endothelial cells. Two pro-angiogenic factors JAG1 and PDGFA are key mediators for KDM2A to enhance angiogenesis. Finally, inhibition of KDM2A significantly decreased tumor growth and angiogenesis in orthotopic animal experiments. Collectively, we conclude that KDM2A functions as an oncogene in breast cancer by upregulating JAG1 to promote stemness, chemoresistance and angiogenesis. PMID:27029061

  10. Multiscale and multi-modality visualization of angiogenesis in a human breast cancer model.

    PubMed

    Cebulla, Jana; Kim, Eugene; Rhie, Kevin; Zhang, Jiangyang; Pathak, Arvind P

    2014-07-01

    Angiogenesis in breast cancer helps fulfill the metabolic demands of the progressing tumor and plays a critical role in tumor metastasis. Therefore, various imaging modalities have been used to characterize tumor angiogenesis. While micro-CT (μCT) is a powerful tool for analyzing the tumor microvascular architecture at micron-scale resolution, magnetic resonance imaging (MRI) with its sub-millimeter resolution is useful for obtaining in vivo vascular data (e.g. tumor blood volume and vessel size index). However, integration of these microscopic and macroscopic angiogenesis data across spatial resolutions remains challenging. Here we demonstrate the feasibility of 'multiscale' angiogenesis imaging in a human breast cancer model, wherein we bridge the resolution gap between ex vivo μCT and in vivo MRI using intermediate resolution ex vivo MR microscopy (μMRI). To achieve this integration, we developed suitable vessel segmentation techniques for the ex vivo imaging data and co-registered the vascular data from all three imaging modalities. We showcase two applications of this multiscale, multi-modality imaging approach: (1) creation of co-registered maps of vascular volume from three independent imaging modalities, and (2) visualization of differences in tumor vasculature between viable and necrotic tumor regions by integrating μCT vascular data with tumor cellularity data obtained using diffusion-weighted MRI. Collectively, these results demonstrate the utility of 'mesoscopic' resolution μMRI for integrating macroscopic in vivo MRI data and microscopic μCT data. Although focused on the breast tumor xenograft vasculature, our imaging platform could be extended to include additional data types for a detailed characterization of the tumor microenvironment and computational systems biology applications.

  11. Intracellular Expression of PAI-1 Specific Aptamers Alters Breast Cancer Cell Migration, Invasion and Angiogenesis

    PubMed Central

    Fortenberry, Yolanda M.; Brandal, Stephanie M.; Carpentier, Gilles; Hemani, Malvi; Pathak, Arvind P.

    2016-01-01

    Plasminogen activator inhibitor-1 (PAI-1) is elevated in various cancers, where it has been shown to effect cell migration and invasion and angiogenesis. While, PAI-1 is a secreted protein, its intercellular levels are increased in cancer cells. Consequently, intracellular PAI-1 could contribute to cancer progression. While various small molecule inhibitors of PAI-1 are currently being investigated, none specifically target intracellular PAI-1. A class of inhibitors, termed aptamers, has been used effectively in several clinical applications. We previously generated RNA aptamers that target PAI-1 and demonstrated their ability to inhibit extracellular PAI-1. In the current study we explored the effect of these aptamers on intracellular PAI-1. We transiently transfected the PAI-1 specific aptamers into both MDA-MB-231 human breast cancer cells, and human umbilical vein endothelial cells (HUVECs) and studied their effects on cell migration, invasion and angiogenesis. Aptamer expressing MDA-MB-231 cells exhibited a decrease in cell migration and invasion. Additionally, intracellular PAI-1 and urokinase plasminogen activator (uPA) protein levels decreased, while the PAI-1/uPA complex increased. Moreover, a significant decrease in endothelial tube formation in HUVECs transfected with the aptamers was observed. In contrast, conditioned media from aptamer transfected MDA-MB-231 cells displayed a slight pro-angiogenic effect. Collectively, our study shows that expressing functional aptamers inside breast and endothelial cells is feasible and may exhibit therapeutic potential. PMID:27755560

  12. A Model for Breast Cancer-Induced Angiogenesis

    DTIC Science & Technology

    1999-09-01

    M ., Roesel, J. L ., Benz, rally) regulated. For instance, our data show that PD-ECGF C., Mueller, H., Matter, A., Zuber, M ., Luescher, K., Litschgi, M ...Harris, A. L ., and Bicknell, R. 2. Heffelfimger, S. C., Yassin, R., Miller, M . A., and Lower, E. Vascu- Thymidine phosphorylase is angiogenic and promotes... Gullino , P. M . Neovascularization induced by breast precancerous? Arch. Pathol. Lab, Med., 110: 171-173, 1985. intraocular xenografts of normal

  13. [Amphiregulin antisense RNA expression inhibits angiogenesis of human breast cancer in nude mice].

    PubMed

    Ma, Lin; Serova, Maria; Podgorniak, Marie Pierre; Berthois, Yolande; Mourah, Samia; Calvo, Fabien

    2005-09-01

    To investigate the anti-angiogenic effect of amphiregulin (AR) antisense RNA expression in breast cancer. Human AR cDNA antisense plasmid was transfected into NS2T2A1 cells (a human breast cancer cell line). Two selected clones expressed AR antisense RNA (AR AS1 and AR AS3 cell lines) in which AR protein expression was reduced. Control cell line NS2T2A1 V was obtained by empty vector transfection. These cells were injected subcutaneously into nude mice. The effects of conditioned media on proliferation of human microvascular endothelial cells (HMEC) were evaluated and VEGF secreted by the cells was measured by ELISA method. In tumor tissues, VEGF expression levels were measured by quantitative RT-PCR, and CD31-immunostaining was used for intra-tumoral vascular quantification. The proliferation index of HMEC cells grown in conditioned media with AR AS1 and AR AS3 was significantly reduced in comparison with that of control cells, accompanied by a decreased VEGF secretion. In tumors derived from AR AS1 and AR AS3 cells, intra-tumoral vascularization was reduced to about 50% of that derived from control cell line, accompanied with a decrease of VEGF expression. Amphiregulin antisense RNA expression inhibits efficiently the angiogenesis in breast cancer, suggesting this growth factor could represent a novel therapeutic target in breast cancer.

  14. A Model for Breast Cancer-Induced Angiogenesis

    DTIC Science & Technology

    1997-09-01

    524, 1990. 17. Terman BI, Carrion ME, Kovacs E, Rasmussen BA, Eddy RL, Shows TB. Identification of a new endothelial cell growth factor receptor...tetradecanoyl-phorbol-13-acetate on adhesiveness and lung-colonizing ability of Lewis lung carcinoma cells. Cancer Res 46:375-380. iV61 Tamaoki T, Nomoto H

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

    PubMed

    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

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

    PubMed Central

    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

    2015-01-01

    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 5×106 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 low frequency 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 high frequency 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

  17. Inhibition of hyperglycemia-induced angiogenesis and breast cancer tumor growth by systemic injection of microRNA-467 antagonist.

    PubMed

    Krukovets, Irene; Legerski, Matthew; Sul, Pavel; Stenina-Adognravi, Olga

    2015-09-01

    Abnormal angiogenesis in multiple tissues is a key characteristic of the vascular complications of diabetes. However, angiogenesis may be increased in one tissue but decreased in another in the same patient at the same time point in the disease. The mechanisms of aberrant angiogenesis in diabetes are not understood. There are no selective therapeutic approaches to target increased neovascularization without affecting physiologic angiogenesis and angiogenesis in ischemic tissues. We recently reported a novel miRNA-dependent pathway that up-regulates angiogenesis in response to hyperglycemia in a cell- and tissue-specific manner. The goal of the work described herein was to test whether systemic administration of an antagonist of miR-467 would prevent hyperglycemia-induced local angiogenesis in a tissue-specific manner. We examined the effect of the antagonist on hyperglycemia-induced tumor growth and angiogenesis and on skin wound healing in mouse models of diabetes. Our data demonstrated that the systemic injection of the antagonist prevented hyperglycemia-induced angiogenesis and growth of mouse and human breast cancer tumors, where the miR-467 pathway was active in hyperglycemia. In tissues where the miR-467-dependent mechanism was not activated by hyperglycemia, there was no effect of the antagonist: the systemic injection did not affect skin wound healing or the growth of prostate tumors. The data show that systemic administration of the miR-467 antagonist could be a breakthrough approach in the treatment and prevention of diabetes-associated breast cancer in a tissue-specific manner without affecting physiologic angiogenesis and angiogenesis in ischemic tissues.

  18. Estrogen receptor beta inhibits angiogenesis and growth of T47D breast cancer xenografts.

    PubMed

    Hartman, Johan; Lindberg, Karolina; Morani, Andrea; Inzunza, José; Ström, Anders; Gustafsson, Jan-Ake

    2006-12-01

    Estrogens, which are stimulators of growth of both the normal breast and malignant breast, mediate their effects through two estrogen receptors (ER), namely ERalpha and ERbeta. ERalpha mediates the proliferative effect of estrogen in breast cancer cells, whereas ERbeta seems to be antiproliferative. We engineered ERalpha-positive T47D breast cancer cells to express ERbeta in a Tet-Off-regulated manner. These cells were then injected orthotopically into severe combined immunodeficient mice, and the growth of the resulting tumors was compared with tumors resulting from injecting the parental T47D cells that do not express ERbeta. The presence of ERbeta resulted in a reduction in tumor growth. Comparison of the ERbeta-expressing and non-ERbeta-expressing tumors revealed that the expression of ERbeta caused a reduction in the number of intratumoral blood vessels and a decrease in expression of the proangiogenic factors vascular endothelial growth factor (VEGF) and platelet-derived growth factor beta (PDGFbeta). In cell culture, with the Tet-Off-regulated ERbeta-expressing cells, expression of ERbeta decreased expression of VEGF and PDGFbeta mRNA under normoxic as well as hypoxic conditions and reduced secreted VEGF and PDGFbeta proteins in cell culture medium. Transient transfection assays with 1,026 bp VEGF and 1,006 bp PDGFbeta promoter constructs revealed a repressive effect of ERbeta at the promoter level of these genes. Taken together, these data show that introduction of ERbeta into malignant cells inhibits their growth and prevents tumor expansion by inhibiting angiogenesis.

  19. Xanthatin, a novel potent inhibitor of VEGFR2 signaling, inhibits angiogenesis and tumor growth in breast cancer cells.

    PubMed

    Yu, Yao; Yu, Jing; Pei, Chong Gang; Li, Yun Yan; Tu, Ping; Gao, Gui Ping; Shao, Yi

    2015-01-01

    Anti-angiogenesis targeting vascular endothelial growth factor receptor 2 (VEGFR2) has emerged as an important tool for cancer treatment. In this study, we described a novel VEGFR2 inhibitor, xanthatin, which inhibits tumor angiogenesis and growth. The biochemical profiles of xanthatin were investigated using kinase assay, migration assay, tube formation, Matrigel plug assay, western blot, immunofluorescence and human tumor xenograft model. Xanthatin significantly inhibited growth, migration and tube formation of human umbilical vascular endothelial cell as well as inhibited vascular endothelial growth factor (VEGF)-stimulated angiogenesis. In addition, it inhibited VEGF-induced phosphorylation of VEGFR2 and its downstream signaling regulator. Moreover, xanthatin directly inhibit proliferation of breast cancer cells MDA-MB-231. Oral administration of xanthatin could markedly inhibit human tumor xenograft growth and decreased microvessel densities (MVD) in tumor sections. Taken together, these preclinical evaluations suggest that xanthatin inhibits angiogenesis and may be a promising anticancer drug candidate.

  20. Autoantibodies against Muscarinic Receptors in Breast Cancer: Their Role in Tumor Angiogenesis

    PubMed Central

    Lombardi, María Gabriela; Negroni, María Pía; Pelegrina, Laura Tatiana; Castro, María Ester; Fiszman, Gabriel L.; Azar, María Eugenia; Morgado, Carlos Cresta; Sales, María Elena

    2013-01-01

    The presence of autoantibodies in cancer has become relevant in recent years. We demonstrated that autoantibodies purified from the sera of breast cancer patients activate muscarinic acetylcholine receptors in tumor cells. Immunoglobulin G (IgG) from breast cancer patients in T1N0Mx stage (tumor size≤2 cm, without lymph node metastasis) mimics the action of the muscarinic agonist carbachol stimulating MCF-7 cell proliferation, migration and invasion. Angiogenesis is a central step in tumor progression because it promotes tumor invasion and metastatic spread. Vascular endothelial growth factor-A (VEGF-A) is the main angiogenic mediator, and its levels have been correlated with poor prognosis in cancer. The aim of the present work was to investigate the effect of T1N0Mx-IgG on the expression of VEGF-A, and the in vivo neovascular response triggered by MCF-7 cells, via muscarinic receptor activation. We demonstrated that T1N0Mx-IgG (10−8 M) and carbachol (10−9 M) increased the constitutive expression of VEGF-A in tumor cells, effect that was reverted by the muscarinic antagonist atropine. We also observed that T1N0Mx-IgG and carbachol enhanced the neovascular response produced by MCF-7 cells in the skin of NUDE mice. The action of IgG or carbachol was reduced in the presence of atropine. In conclusion, T1N0Mx-IgG and carbachol may promote VEGF-A production and neovascularization induced by breast tumor cells via muscarinic receptors activation. These effects may be accelerating breast tumor progression. PMID:23460876

  1. Autoantibodies against muscarinic receptors in breast cancer: their role in tumor angiogenesis.

    PubMed

    Lombardi, María Gabriela; Negroni, María Pía; Pelegrina, Laura Tatiana; Castro, María Ester; Fiszman, Gabriel L; Azar, María Eugenia; Morgado, Carlos Cresta; Sales, María Elena

    2013-01-01

    The presence of autoantibodies in cancer has become relevant in recent years. We demonstrated that autoantibodies purified from the sera of breast cancer patients activate muscarinic acetylcholine receptors in tumor cells. Immunoglobulin G (IgG) from breast cancer patients in T1N0Mx stage (tumor size≤2 cm, without lymph node metastasis) mimics the action of the muscarinic agonist carbachol stimulating MCF-7 cell proliferation, migration and invasion. Angiogenesis is a central step in tumor progression because it promotes tumor invasion and metastatic spread. Vascular endothelial growth factor-A (VEGF-A) is the main angiogenic mediator, and its levels have been correlated with poor prognosis in cancer. The aim of the present work was to investigate the effect of T1N0Mx-IgG on the expression of VEGF-A, and the in vivo neovascular response triggered by MCF-7 cells, via muscarinic receptor activation. We demonstrated that T1N0Mx-IgG (10(-8) M) and carbachol (10(-9) M) increased the constitutive expression of VEGF-A in tumor cells, effect that was reverted by the muscarinic antagonist atropine. We also observed that T1N0Mx-IgG and carbachol enhanced the neovascular response produced by MCF-7 cells in the skin of NUDE mice. The action of IgG or carbachol was reduced in the presence of atropine. In conclusion, T1N0Mx-IgG and carbachol may promote VEGF-A production and neovascularization induced by breast tumor cells via muscarinic receptors activation. These effects may be accelerating breast tumor progression.

  2. Targeting Notch1 inhibits invasion and angiogenesis of human breast cancer cells via inhibition Nuclear Factor-κB signaling

    PubMed Central

    Liu, Yuan; Su, Chuanfu; Shan, Yuqing; Yang, Shouxiang; Ma, Guifeng

    2016-01-01

    Notch-1, a type-1 transmembrane protein, plays critical roles in the pathogenesis and progression of human malignancies, including breast cancer; however, the precise mechanism by which Notch-1 causes tumor cell invasion and angiogenesis remain unclear. Nuclear factor-κB (NF-κB), interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMP) are critically involved in the processes of tumor cell invasion and metastasis, we investigated whether targeting Notch-1 could be mechanistically associated with the down-regulation of NF-κB, IL-8, VEGF, and MMP-9, resulting in the inhibition of invasion and angiogenesis of breast cancer cells. Our data showed that down-regulation of Notch-1 leads to the inactivation of NF-κB activity and inhibits the expression of its target genes, such as IL-8, VEGF and MMP-9. We also found that down-regulation of Notch-1 decreased cell invasion, and vice versa Consistent with these results, we also found that the down-regulation of Notch-1 not only decreased MMP-9 mRNA and its protein expression but also inhibited MMP-9 active form. Moreover, conditioned medium from Notch-1 siRNA-transfected breast cancer cells showed reduced levels of IL-8 and VEGF and, in turn, inhibited the tube formation of HUVECs, suggesting that down-regulation of Notch-1 leads to the inhibition of angiogenesis. Furthermore, conditioned medium from Notch-1 cDNA-transfected breast cancer cells showed increased levels of IL-8 and VEGF and, in turn, promoted the tube formation of HUVECs, suggesting that Notch-1 overexpression leads to the promotion of angiogenesis.We therefore concluded that down-regulation of Notch-1 leads to the inactivation NF-κB and its target genes (IL-8, MMP-9 and VEGF), resulting in the inhibition of invasion and angiogenesis. PMID:27398151

  3. Dual targeting of ANGPT1 and TGFBR2 genes by miR-204 controls angiogenesis in breast cancer.

    PubMed

    Flores-Pérez, Ali; Marchat, Laurence A; Rodríguez-Cuevas, Sergio; Bautista-Piña, Verónica; Hidalgo-Miranda, Alfredo; Ocampo, Elena Aréchaga; Martínez, Mónica Sierra; Palma-Flores, Carlos; Fonseca-Sánchez, Miguel A; Astudillo-de la Vega, Horacio; Ruíz-García, Erika; González-Barrios, Juan Antonio; Pérez-Plasencia, Carlos; Streber, María L; López-Camarillo, César

    2016-10-05

    Deregulated expression of microRNAs has been associated with angiogenesis. Studying the miRNome of locally advanced breast tumors we unsuspectedly found a dramatically repression of miR-204, a small non-coding RNA with no previous involvement in tumor angiogenesis. Downregulation of miR-204 was confirmed in an independent cohort of patients and breast cancer cell lines. Gain-of-function analysis indicates that ectopic expression of miR-204 impairs cell proliferation, anchorage-independent growth, migration, invasion, and the formation of 3D capillary networks in vitro. Likewise, in vivo vascularization and angiogenesis were suppressed by miR-204 in a nu/nu mice model. Genome-wide profiling of MDA-MB-231 cells expressing miR-204 revealed changes in the expression of hundred cancer-related genes. Of these, we focused on the study of pro-angiogenic ANGPT1 and TGFβR2. Functional analysis using luciferase reporter and rescue assays confirmed that ANGPT1 and TGFβR2 are novel effectors downstream of miR-204. Accordingly, an inverse correlation between miR-204 and ANGPT1/TGFβR2 expression was found in breast tumors. Knockdown of TGFβR2, but not ANGPT1, impairs cell proliferation and migration whereas inhibition of both genes inhibits angiogenesis. Taken altogether, our findings reveal a novel role for miR-204/ANGPT1/TGFβR2 axis in tumor angiogenesis. We propose that therapeutic manipulation of miR-204 levels may represent a promising approach in breast cancer.

  4. Dual targeting of ANGPT1 and TGFBR2 genes by miR-204 controls angiogenesis in breast cancer

    PubMed Central

    Flores-Pérez, Ali; Marchat, Laurence A.; Rodríguez-Cuevas, Sergio; Bautista-Piña, Verónica; Hidalgo-Miranda, Alfredo; Ocampo, Elena Aréchaga; Martínez, Mónica Sierra; Palma-Flores, Carlos; Fonseca-Sánchez, Miguel A.; Astudillo-de la Vega, Horacio; Ruíz-García, Erika; González-Barrios, Juan Antonio; Pérez-Plasencia, Carlos; Streber, María L.; López-Camarillo, César

    2016-01-01

    Deregulated expression of microRNAs has been associated with angiogenesis. Studying the miRNome of locally advanced breast tumors we unsuspectedly found a dramatically repression of miR-204, a small non-coding RNA with no previous involvement in tumor angiogenesis. Downregulation of miR-204 was confirmed in an independent cohort of patients and breast cancer cell lines. Gain-of-function analysis indicates that ectopic expression of miR-204 impairs cell proliferation, anchorage-independent growth, migration, invasion, and the formation of 3D capillary networks in vitro. Likewise, in vivo vascularization and angiogenesis were suppressed by miR-204 in a nu/nu mice model. Genome-wide profiling of MDA-MB-231 cells expressing miR-204 revealed changes in the expression of hundred cancer-related genes. Of these, we focused on the study of pro-angiogenic ANGPT1 and TGFβR2. Functional analysis using luciferase reporter and rescue assays confirmed that ANGPT1 and TGFβR2 are novel effectors downstream of miR-204. Accordingly, an inverse correlation between miR-204 and ANGPT1/TGFβR2 expression was found in breast tumors. Knockdown of TGFβR2, but not ANGPT1, impairs cell proliferation and migration whereas inhibition of both genes inhibits angiogenesis. Taken altogether, our findings reveal a novel role for miR-204/ANGPT1/TGFβR2 axis in tumor angiogenesis. We propose that therapeutic manipulation of miR-204 levels may represent a promising approach in breast cancer. PMID:27703260

  5. A novel bisindole-PBD conjugate inhibits angiogenesis by regulating STAT3 and VEGF in breast cancer cells.

    PubMed

    Sarma, Pranjal; Ramaiah, M Janaki; Pal, Dhananjaya; Bhadra, Utpal; Pal Bhadra, Manika

    2016-04-15

    Breast cancer is highly resistant to chemotherapeutic approach and hence, alternative strategies have been developed to fight against this heterogeneous group of disease. In particular, many studies have demonstrated about various drugs for the treatment of breast cancer. In our study, we assessed the anti-angiogenenic activities of Bisindole-PBD (5b) in MCF-7 and MDA-MB-231 cell lines. In vitro Endothelial Cell (HUVEC) Tube Formation Assay was performed to show inhibitory role of 5b along with its role upon wound healing process in breast cancer cells in vitro. Semi-quantitative reverse transcription PCR (RT-PCR) was also done to examine the expression of VEGF in response to 5b in breast cancer cells and in HUVEC cells. siRNA transfection study explored STAT3 mediated VEGF transcription in breast cancer cells MCF-7 and MDA-MB-231. CAM assay was performed to see the role of 5b on vessel formation in chicken embryo. From in vitro data we have demonstrated that 5b played a role in regulation of breast cancer cell proliferation by inhibiting angiogenesis. Test drug 5b suppressed the expression VEGF at both transcriptional and post transcriptional levels. Apart from this, there was significant down regulation in STAT3 level after drug treatment, which was found to be involved in the VEGF transcription. Metastasis related MMP-2 and MMP-9 expressions were also modulated by 5b. In vivo study by Chick Chorioallantoic Membrane (CAM) Assay also showed anti-angiogenesis role of the test drug which was consistent with the in vitro data. Altogether, our data demonstrated 5b as potent small molecule with anti-angiogenic activities. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Inositol 1, 4, 5-trisphosphate-dependent nuclear calcium signals regulate angiogenesis and cell motility in triple negative breast cancer.

    PubMed

    Guimarães, Erika; Machado, Rodrigo; Fonseca, Matheus de Castro; França, Andressa; Carvalho, Clarissa; Araújo E Silva, Ana Cândida; Almeida, Brígida; Cassini, Puebla; Hissa, Bárbara; Drumond, Luciana; Gonçalves, Carlos; Fernandes, Gabriel; De Brot, Marina; Moraes, Márcio; Barcelos, Lucíola; Ortega, José Miguel; Oliveira, André; Leite, M Fátima

    2017-01-01

    Increases in nuclear calcium concentration generate specific biological outcomes that differ from those resulting from increased cytoplasmic calcium. Nuclear calcium effects on tumor cell proliferation are widely appreciated; nevertheless, its involvement in other steps of tumor progression is not well understood. Therefore, we evaluated whether nuclear calcium is essential in other additional stages of tumor progression, including key steps associated with the formation of the primary tumor or with the metastatic cascade. We found that nuclear calcium buffering impaired 4T1 triple negative breast cancer growth not just by decreasing tumor cell proliferation, but also by enhancing tumor necrosis. Moreover, nuclear calcium regulates tumor angiogenesis through a mechanism that involves the upregulation of the anti-angiogenic C-X-C motif chemokine 10 (CXCL10-IP10). In addition, nuclear calcium buffering regulates breast tumor cell motility, culminating in less cell invasion, likely due to enhanced vinculin expression, a focal adhesion structural protein. Together, our results show that nuclear calcium is essential for triple breast cancer angiogenesis and cell migration and can be considered as a promising strategic target for triple negative breast cancer therapy.

  7. Inositol 1, 4, 5-trisphosphate-dependent nuclear calcium signals regulate angiogenesis and cell motility in triple negative breast cancer

    PubMed Central

    Fonseca, Matheus de Castro; França, Andressa; Carvalho, Clarissa; Araújo e Silva, Ana Cândida; Almeida, Brígida; Cassini, Puebla; Hissa, Bárbara; Drumond, Luciana; Gonçalves, Carlos; Fernandes, Gabriel; De Brot, Marina; Moraes, Márcio; Barcelos, Lucíola; Ortega, José Miguel; Oliveira, André; Leite, M. Fátima

    2017-01-01

    Increases in nuclear calcium concentration generate specific biological outcomes that differ from those resulting from increased cytoplasmic calcium. Nuclear calcium effects on tumor cell proliferation are widely appreciated; nevertheless, its involvement in other steps of tumor progression is not well understood. Therefore, we evaluated whether nuclear calcium is essential in other additional stages of tumor progression, including key steps associated with the formation of the primary tumor or with the metastatic cascade. We found that nuclear calcium buffering impaired 4T1 triple negative breast cancer growth not just by decreasing tumor cell proliferation, but also by enhancing tumor necrosis. Moreover, nuclear calcium regulates tumor angiogenesis through a mechanism that involves the upregulation of the anti-angiogenic C-X-C motif chemokine 10 (CXCL10-IP10). In addition, nuclear calcium buffering regulates breast tumor cell motility, culminating in less cell invasion, likely due to enhanced vinculin expression, a focal adhesion structural protein. Together, our results show that nuclear calcium is essential for triple breast cancer angiogenesis and cell migration and can be considered as a promising strategic target for triple negative breast cancer therapy. PMID:28376104

  8. MiR-578 and miR-573 as potential players in BRCA-related breast cancer angiogenesis.

    PubMed

    Danza, Katia; De Summa, Simona; Pinto, Rosamaria; Pilato, Brunella; Palumbo, Orazio; Merla, Giuseppe; Simone, Gianni; Tommasi, Stefania

    2015-01-01

    The involvement of microRNA (miRNAs), a new class of small RNA molecules, in governing angiogenesis has been well described. Our aim was to investigate miRNA-mediated regulation of angiogenesis in a series of familial breast cancers stratified by BRCA1/2 mutational status in BRCA carriers and BRCA non-carriers (BRCAX). Affymetrix GeneChip miRNA Arrays were used to perform miRNA expression analysis on 43 formalin-fixed paraffin-embedded (FFPE) tumour tissue familial breast cancers (22 BRCA 1/2-related and 21 BRCAX). Pathway enrichment analysis was carried out with the DIANA miRPath v2.0 web-based computational tool, and the miRWalk database was used to identify target genes of deregulated miRNAs. An independent set of 8 BRCA 1/2-related and 11 BRCAX breast tumors was used for validation by Real-Time PCR. In vitro analysis on HEK293, MCF-7 and SUM149PT cells were performed to best-clarify miR-573 and miR-578 role. A set of 16 miRNAs differentially expressed between BRCA 1/2-related and BRCAX breast tumors emerged from the profile analysis. Among these, miR-578 and miR-573 were found to be down-regulated in BRCA 1/2-related breast cancer and associated to the Focal adhesion, Vascular Endothelial Growth Factor (VEGF) and Hypoxia Inducible Factor-1 (HIF-1) signaling pathways. Our data highlight the role of miR-578 and miR-573 in controlling BRCA 1/2-related angiogenesis by targeting key regulators of Focal adhesion, VEGF and HIF-1 signaling pathways.

  9. MiR-578 and miR-573 as potential players in BRCA-related breast cancer angiogenesis

    PubMed Central

    Danza, Katia; Summa, Simona De; Pinto, Rosamaria; Pilato, Brunella; Palumbo, Orazio; Merla, Giuseppe; Simone, Gianni; Tommasi, Stefania

    2015-01-01

    The involvement of microRNA (miRNAs), a new class of small RNA molecules, in governing angiogenesis has been well described. Our aim was to investigate miRNA-mediated regulation of angiogenesis in a series of familial breast cancers stratified by BRCA1/2 mutational status in BRCA carriers and BRCA non-carriers (BRCAX). Affymetrix GeneChip miRNA Arrays were used to perform miRNA expression analysis on 43 formalin-fixed paraffin-embedded (FFPE) tumour tissue familial breast cancers (22 BRCA 1/2-related and 21 BRCAX). Pathway enrichment analysis was carried out with the DIANA miRPath v2.0 web-based computational tool, and the miRWalk database was used to identify target genes of deregulated miRNAs. An independent set of 8 BRCA 1/2-related and 11 BRCAX breast tumors was used for validation by Real-Time PCR. In vitro analysis on HEK293, MCF-7 and SUM149PT cells were performed to best-clarify miR-573 and miR-578 role. A set of 16 miRNAs differentially expressed between BRCA 1/2-related and BRCAX breast tumors emerged from the profile analysis. Among these, miR-578 and miR-573 were found to be down-regulated in BRCA 1/2-related breast cancer and associated to the Focal adhesion, Vascular Endothelial Growth Factor (VEGF) and Hypoxia Inducible Factor-1 (HIF-1) signaling pathways. Our data highlight the role of miR-578 and miR-573 in controlling BRCA 1/2-related angiogenesis by targeting key regulators of Focal adhesion, VEGF and HIF-1 signaling pathways. PMID:25333258

  10. Phellinus linteus suppresses growth, angiogenesis and invasive behaviour of breast cancer cells through the inhibition of AKT signalling

    PubMed Central

    Sliva, D; Jedinak, A; Kawasaki, J; Harvey, K; Slivova, V

    2008-01-01

    The antitumour activity of a medicinal mushroom Phellinus linteus (PL), through the stimulation of immune system or the induction of apoptosis, has been recently described. However, the molecular mechanisms responsible for the inhibition of invasive behaviour of cancer cells remain to be addressed. In the present study, we demonstrate that PL inhibits proliferation (anchorage-dependent growth) as well as colony formation (anchorage-independent growth) of highly invasive human breast cancer cells. The growth inhibition of MDA-MB-231 cells is mediated by the cell cycle arrest at S phase through the upregulation of p27Kip1 expression. Phellinus linteus also suppressed invasive behaviour of MDA-MB-231 cells by the inhibition of cell adhesion, cell migration and cell invasion through the suppression of secretion of urokinase-plasminogen activator from breast cancer cells. In addition, PL markedly inhibited the early event in angiogenesis, capillary morphogenesis of the human aortic endothelial cells, through the downregulation of secretion of vascular endothelial growth factor from MDA-MB-231 cells. These effects are mediated by the inhibition of serine-threonine kinase AKT signalling, because PL suppressed phosphorylation of AKT at Thr308 and Ser473 in breast cancer cells. Taken together, our study suggests potential therapeutic effect of PL against invasive breast cancer. PMID:18362935

  11. Phellinus linteus suppresses growth, angiogenesis and invasive behaviour of breast cancer cells through the inhibition of AKT signalling.

    PubMed

    Sliva, D; Jedinak, A; Kawasaki, J; Harvey, K; Slivova, V

    2008-04-22

    The antitumour activity of a medicinal mushroom Phellinus linteus (PL), through the stimulation of immune system or the induction of apoptosis, has been recently described. However, the molecular mechanisms responsible for the inhibition of invasive behaviour of cancer cells remain to be addressed. In the present study, we demonstrate that PL inhibits proliferation (anchorage-dependent growth) as well as colony formation (anchorage-independent growth) of highly invasive human breast cancer cells. The growth inhibition of MDA-MB-231 cells is mediated by the cell cycle arrest at S phase through the upregulation of p27(Kip1) expression. Phellinus linteus also suppressed invasive behaviour of MDA-MB-231 cells by the inhibition of cell adhesion, cell migration and cell invasion through the suppression of secretion of urokinase-plasminogen activator from breast cancer cells. In addition, PL markedly inhibited the early event in angiogenesis, capillary morphogenesis of the human aortic endothelial cells, through the downregulation of secretion of vascular endothelial growth factor from MDA-MB-231 cells. These effects are mediated by the inhibition of serine-threonine kinase AKT signalling, because PL suppressed phosphorylation of AKT at Thr(308) and Ser(473) in breast cancer cells. Taken together, our study suggests potential therapeutic effect of PL against invasive breast cancer.

  12. The transcription factor GATA1 and the histone methyltransferase SET7 interact to promote VEGF-mediated angiogenesis and tumor growth and predict clinical outcome of breast cancer.

    PubMed

    Zhang, Yanan; Liu, Jie; Lin, Jing; Zhou, Lei; Song, Yuhua; Wei, Bo; Luo, Xiaoli; Chen, Zhida; Chen, Yingjie; Xiong, Jiaxiu; Xu, Xiaojie; Ding, Lihua; Ye, Qinong

    2016-03-01

    Angiogenesis is essential for tumor growth. Vascular endothelial growth factor (VEGF) is the most important regulator of tumor angiogenesis. However, how transcription factors interact with histone-modifying enzymes to regulate VEGF transcription and tumor angiogenesis remains unclear. Here, we show that transcription factor GATA1 associates with the histone methyltransferase SET7 to promote VEGF transcription and breast tumor angiogenesis. Using chromatin immunoprecipitation assay, we found that GATA1 was required for recruitment of SET7, RNA polymerase II and transcription factor II B to VEGF core promoter. GATA1 enhanced breast cancer cell (MCF7, ZR75-1 and MDA-MB-231)-secreted VEGF via SET7, which promoted vascular endothelial cell (HUVEC) proliferation, migration and tube formation. SET7 was required for GATA1-induced breast tumor angiogenesis and growth in nude mice. Immunohistochemical staining showed that expression of GATA1 and SET7 was upregulated and positively correlated with VEGF expression and microvessel number in 80 breast cancer patients. GATA1 and SET7 are independent poor prognostic factors in breast cancer. Our data provide novel insights into VEGF transcriptional regulation and suggest GATA1/SET7 as cancer therapeutic targets.

  13. The quorum sensing peptides PhrG, CSP and EDF promote angiogenesis and invasion of breast cancer cells in vitro.

    PubMed

    De Spiegeleer, Bart; Verbeke, Frederick; D'Hondt, Matthias; Hendrix, An; Van De Wiele, Christophe; Burvenich, Christian; Peremans, Kathelijne; De Wever, Olivier; Bracke, Marc; Wynendaele, Evelien

    2015-01-01

    The role of the human microbiome on cancer progression remains unclear. Therefore, in this study, we investigated the influence of some quorum sensing peptides, produced by diverse commensal or pathogenic bacteria, on breast cancer cell invasion and thus cancer outcome. Based on microscopy, transcriptome and Chick Chorioallantoic Membrane (CAM) analyses, four peptides (PhrG from B. subtilis, CSP from S. mitis and EDF from E. coli, together with its tripeptide analogue) were found to promote tumour cell invasion and angiogenesis, thereby potentially influencing tumour metastasis. Our results offer not only new insights on the possible role of the microbiome, but also further opportunities in cancer prevention and therapy by competing with these endogenous molecules and/or by modifying people's life style.

  14. The Quorum Sensing Peptides PhrG, CSP and EDF Promote Angiogenesis and Invasion of Breast Cancer Cells In Vitro

    PubMed Central

    De Spiegeleer, Bart; Verbeke, Frederick; D’Hondt, Matthias; Hendrix, An; Van De Wiele, Christophe; Burvenich, Christian; Peremans, Kathelijne; De Wever, Olivier; Bracke, Marc; Wynendaele, Evelien

    2015-01-01

    The role of the human microbiome on cancer progression remains unclear. Therefore, in this study, we investigated the influence of some quorum sensing peptides, produced by diverse commensal or pathogenic bacteria, on breast cancer cell invasion and thus cancer outcome. Based on microscopy, transcriptome and Chick Chorioallantoic Membrane (CAM) analyses, four peptides (PhrG from B. subtilis, CSP from S. mitis and EDF from E. coli, together with its tripeptide analogue) were found to promote tumour cell invasion and angiogenesis, thereby potentially influencing tumour metastasis. Our results offer not only new insights on the possible role of the microbiome, but also further opportunities in cancer prevention and therapy by competing with these endogenous molecules and/or by modifying people’s life style. PMID:25780927

  15. Sphingosine-1-phosphate produced by sphingosine kinase 1 promotes breast cancer progression by stimulating angiogenesis and lymphangiogenesis

    PubMed Central

    Nagahashi, Masayuki; Ramachandran, Subramaniam; Kim, Eugene Y.; Allegood, Jeremy C.; Rashid, Omar M.; Yamada, Akimitsu; Zhao, Renping; Milstien, Sheldon; Zhou, Huiping; Spiegel, Sarah; Takabe, Kazuaki

    2011-01-01

    Sphingosine-1-phosphate (S1P) is a pleiotropic bioactive lipid mediator that promotes breast cancer progression by diverse mechanisms that remain somewhat unclear. Here we report pharmacological evidence of a critical role for sphingosine kinase 1 (SphK1) in producing S1P and mediating tumor-induced hemangiogenesis and lymphangiogenesis in a murine model of breast cancer metastasis. S1P levels increased both in the tumor and the circulation. In agreement, serum S1P levels were significantly elevated in stage IIIA human breast cancer patients, compared to age/ethnicity-matched healthy volunteers. However, treatment with the specific SphK1 inhibitor SK1-I suppressed S1P levels, reduced metastases to lymph nodes and lungs and decreased overall tumor burden of our murine model. Both S1P and angiopoietin 2 (Ang2) stimulated hemangiogenesis and lymphangiogenesis in vitro whereas SK1-I inhibited each process. We quantified both processes in vivo from the same specimen by combining Directed In Vivo Angiogenesis Assays (DIVAA) with Fluorescence Activated Cell Sorting (DIVAA/FACS), thereby confirming the results obtained in vitro. Notably, SK1-I decreased both processes not only at the primary tumor but also in lymph nodes, with peritumoral lymphatic vessel density reduced in SK1-I-treated animals. Taken together, our findings demonstrate that SphK1-produced S1P is a crucial mediator of breast cancer-induced hemangiogenesis and lymphangiogenesis. Our results implicate SphK1 along with S1P as therapeutic targets in breast cancer. PMID:22298596

  16. Induction of Ras by SAF-1/MAZ through a feed-forward loop promotes angiogenesis in breast cancer.

    PubMed

    Ray, Alpana; Ray, Bimal K

    2015-02-01

    In the majority of breast cancers, overexpression and hyperactivation of Ras in the tumor microenvironment play significant role in promoting cancer cell growth, angiogenesis, and metastasis. We have previously shown that vascular endothelial growth factor (VEGF) expression in triple negative breast cancer cells is regulated, at least in part, by SAF-1 (serum amyloid A activating factor 1) transcription factor. In this study we show that transformation of normal MCF-10A breast epithelial cells by constitutively active, oncogenic Ras, induces the DNA-binding activity and transcription function of SAF-1. Furthermore, we show that inhibition of MEK/MAPK-signaling pathway prevents Ras-mediated activation of SAF-1. Interestingly, silencing of SAF-1 expression in breast cancer cells by SAF-1-specific short hairpin RNAs (shRNAs) significantly reduced H-Ras and K-Ras mRNA level. We show that SAF-1 is a direct transcriptional regulator of H-Ras and K-Ras and overexpression of SAF-1 increases H-Ras and K-Ras gene expression. Chromatin immunoprecipitation (ChIP) analyses demonstrated in vivo interaction of SAF-1 at highly purine-rich sequences present at the proximal promoter region, upstream of the transcription start site, in H-Ras and K-Ras genes. Previous studies have shown that these sequences are nuclease hypersensitive and capable of forming G4 quadruplex structure. Together, our results show the presence of a novel transactivating loop, in which, Ras and SAF-1 are interconnected. These findings will help defining molecular mechanisms of abnormal overexpression of Ras in breast tumors, which seldom show genetic Ras mutations. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  17. Polysaccharides from Korean Citrus hallabong peels inhibit angiogenesis and breast cancer cell migration.

    PubMed

    Park, J Y; Shin, M S; Kim, S N; Kim, H Y; Kim, K H; Shin, K S; Kang, K S

    2016-04-01

    Although the peel of the hallabong (Citrus sphaerocarpa) fruit is rich in polysaccharides, which are valuable dietary ingredients for human health, it is normally wasted. The present study aimed to utilize the peel waste and identify properties it may have against breast cancer metastasis. Hallabong peel extract containing crude polysaccharides was fractionated by gel permeation chromatography to produce four different polysaccharide fractions (HBE-I, -II, -III, and -IV). The HBE polysaccharides significantly blocked tube formation of human umbilical vein vascular endothelial cells (HUVECs), at a concentration of 12.5 or 25 μg/mL. Tube formation appeared to be more sensitive to HBE-II than to other HBE polysaccharides. HBE-II also inhibited breast cancer cell migration, through downregulation of matrix metalloproteinase-9 (MMP-9) in MDA-MB-231 triple-negative breast cancer cells. Therefore, inhibition of tube formation and MMP-9-mediated migration observed in HUVEC and MDA-MB-231 cells, respectively, are likely to be important therapeutic targets in triple-negative breast cancer metastasis.

  18. Angiomotin and angiomotin like proteins, their expression and correlation with angiogenesis and clinical outcome in human breast cancer

    PubMed Central

    Jiang, Wen G; Watkins, Gareth; Douglas-Jones, Anthony; Holmgren, Lars; Mansel, Robert E

    2006-01-01

    Backgound Angiomotin is a newly discovered molecule that regulates the migration and tubule formation of endothelial cells. It therefore has been implicated in the control of angiogenesis under physiological and pathological conditions. This study examined the expression of angiomotin and its analogues, angiomotin-like 1 (L1) and -like 2 (L2) in breast tumour tissues, and analysed their correlation with angiogenesis and clinical outcomes. Methods Human breast tissues (normal n = 32 and tumours n = 120) were used. The levels of expression of angiomotin, L1 and L2 were determined using reverse transcription PCR. Microvessels were stained using antibodies against PECAM, von Willebrand factor (factor 8, or vWF) and VE-cadherin. The transcript levels of angiomotin and its analogues were assessed against the clinical and pathological background, including long term survival (120 months). Results Breast cancer tissues expressed significantly higher levels of angiomotin transcript, compared with normal mammary tissues (33.1 ± 11 in normal versus 86.5 ± 13.7 in tumour tissues, p = 0.003). Both L1 and L2 were seen at marginally higher levels in tumour than normal tissues but the difference was not statistically significant. Levels of angiomotin were at significantly higher levels in grade 2 and grade 3 tumours compared with grade 1 (p < 0.01 and p = 0.05 respectively). The levels of angiomotin in tumours from patients who had metastatic disease were also significantly higher than those patients who remained disease free (p = 0.03). Multivariate analysis indicated that angiomotin transcript was an independent prognostic factor (p = 0.031). No significant correlations were seen between angiomotin-L1 and L2 with the clinical outcome. Furthermore, high levels of angiomotin transcript were associated with shorter overall survival (p < 0.05). There was a high degree of correlation between levels of vW factor and that of angiomotin (p < 0.05), but not angiomotin-L1 and angiomotin

  19. Upregulation of miRNA-155 promotes tumour angiogenesis by targeting VHL and is associated with poor prognosis and triple-negative breast cancer

    PubMed Central

    Kong, W; He, L; Richards, EJ; Challa, S; Xu, C-X; Permuth-Wey, J; Lancaster, JM; Coppola, D; Sellers, TA; Djeu, JY; Cheng, JQ

    2014-01-01

    MicroRNA-155 (miR-155) is frequently up-regulated in various types of human cancer; however, its role in cancer angiogenesis remains unknown. Here, we demonstrate the role of miR-155 in angiogenesis through targeting von Hippel-Lindau tumour suppressor (VHL) in breast cancer. Ectopic expression of miR-155 induced whereas knockdown of miR-155 inhibited HUVEC network formation, proliferation, invasion, and migration. Furthermore, mammary fat pad xenotransplantation of ectopically expressed miR-155 resulted in extensive angiogenesis, proliferation, tumour necrosis, and recruitment of pro-inflammatory cells such as tumour associated macrophages. Expression of VHL abrogated these miR-155 effects. Moreover, miR-155 expression inversely correlates with VHL expression level and is associated with late stage, lymph node metastasis, and poor prognosis as well as triple-negative tumour in breast cancer. These findings indicate that miR-155 plays a pivotal role in tumour angiogenesis by downregulation of VHL, and provide a basis for miR-155-expressing tumours to embody an aggressive malignant phenotype, and therefore, miR-155 is an important therapeutic target in breast cancer. PMID:23353819

  20. Exosome-mediated microRNA signaling from breast cancer cells is altered by the anti-angiogenesis agent docosahexaenoic acid (DHA).

    PubMed

    Hannafon, Bethany N; Carpenter, Karla J; Berry, William L; Janknecht, Ralf; Dooley, William C; Ding, Wei-Qun

    2015-07-16

    Docosahexaenoic acid (DHA) is a natural compound with anticancer and anti-angiogenesis activity that is currently under investigation as both a preventative agent and an adjuvant to breast cancer therapy. However, the precise mechanisms of DHA's anticancer activities are unclear. It is understood that the intercommunication between cancer cells and their microenvironment is essential to tumor angiogenesis. Exosomes are extracellular vesicles that are important mediators of intercellular communication and play a role in promoting angiogenesis. However, very little is known about the contribution of breast cancer exosomes to tumor angiogenesis or whether exosomes can mediate DHA's anticancer action. Exosomes were collected from MCF7 and MDA-MB-231 breast cancer cells after treatment with DHA. We observed an increase in exosome secretion and exosome microRNA contents from the DHA-treated cells. The expression of 83 microRNAs in the MCF7 exosomes was altered by DHA (>2-fold). The most abundant exosome microRNAs (let-7a, miR-23b, miR-27a/b, miR-21, let-7, and miR-320b) are known to have anti-cancer and/or anti-angiogenic activity. These microRNAs were also increased by DHA treatment in the exosomes from other breast cancer lines (MDA-MB-231, ZR751 and BT20), but not in exosomes from normal breast cells (MCF10A). When DHA-treated MCF7 cells were co-cultured with or their exosomes were directly applied to endothelial cell cultures, we observed an increase in the expression of these microRNAs in the endothelial cells. Furthermore, overexpression of miR-23b and miR-320b in endothelial cells decreased the expression of their pro-angiogenic target genes (PLAU, AMOTL1, NRP1 and ETS2) and significantly inhibited tube formation by endothelial cells, suggesting that the microRNAs transferred by exosomes mediate DHA's anti-angiogenic action. These effects could be reversed by knockdown of the Rab GTPase, Rab27A, which controls exosome release. We conclude that DHA alters breast

  1. A soluble form of GAS1 inhibits tumor growth and angiogenesis in a triple negative breast cancer model.

    PubMed

    Jiménez, Adriana; López-Ornelas, Adolfo; Estudillo, Enrique; González-Mariscal, Lorenza; González, Rosa O; Segovia, José

    2014-10-01

    We previously demonstrated the capacity of GAS1 (Growth Arrest Specific 1) to inhibit the growth of gliomas by blocking the GDNF-RET signaling pathway. Here, we show that a soluble form of GAS1 (tGAS1), decreases the number of viable MDA MB 231 human breast cancer cells, acting in both autocrine and paracrine manners when secreted from producing cells. Moreover, tGAS1 inhibits the growth of tumors implanted in female nu/nu mice through a RET-independent mechanism which involves interfering with the Artemin (ARTN)-GFRα3-(GDNF Family Receptor alpha 3) mediated intracellular signaling and the activation of ERK. In addition, we observed that the presence of tGAS1 reduces the vascularization of implanted tumors, by preventing the migration of endothelial cells. The present results support a potential adjuvant role for tGAS1 in the treatment of breast cancer, by detaining tumor growth and inhibiting angiogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Imaging tumor angiogenesis in breast cancer experimental lung metastasis with positron emission tomography, near-infrared fluorescence, and bioluminescence

    PubMed Central

    Zhang, Yin; Hong, Hao; Nayak, Tapas R.; Valdovinos, Hector F.; Myklejord, Duane V.; Theuer, Charles P.; Barnhart, Todd E.; Cai, Weibo

    2013-01-01

    The goal of this study was to develop a molecular imaging agent that can allow for both positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging of CD105 expression in metastatic breast cancer. TRC105, a chimeric anti-CD105 monoclonal antibody, was labeled with both a NIRF dye (i.e., IRDye 800CW) and 64Cu to yield 64Cu-NOTA-TRC105-800CW. Flow cytometry analysis revealed no difference in CD105 binding affinity/specificity between TRC105 and NOTA-TRC105-800CW. Serial bioluminescence imaging (BLI) was carried out to non-invasively monitor the lung tumor burden in BALB/c mice, after intravenous injection of firefly luciferase-transfected 4T1 (i.e., fLuc-4T1) murine breast cancer cells to establish the experimental lung metastasis model. Serial PET imaging revealed that fLuc-4T1 lung tumor uptake of 64Cu-NOTA-TRC105-800CW was 11.9 ± 1.2, 13.9 ± 3.9, and 13.4 ± 2.1 %ID/g at 4, 24, and 48 h post-injection respectively (n = 3). Biodistribution studies, blocking fLuc-4T1 lung tumor uptake with excess TRC105, control experiments with 64Cu-NOTA-cetuximab-800CW (which served as an isotype-matched control), ex vivo BLI/PET/NIRF imaging, autoradiography, and histology all confirmed CD105 specificity of 64Cu-NOTA-TRC105-800CW. Successful PET/NIRF imaging of tumor angiogenesis (i.e., CD105 expression) in the breast cancer experimental lung metastasis model warrants further investigation and clinical translation of dual-labeled TRC105-based agents, which can potentially enable early detection of small metastases and image-guided surgery for tumor removal. PMID:23471463

  3. Supernatants of Adipocytes From Obese Versus Normal Weight Women and Breast Cancer Cells: In Vitro Impact on Angiogenesis.

    PubMed

    Bougaret, Lauriane; Delort, Laetitia; Billard, Hermine; Lequeux, Charlotte; Goncalves-Mendes, Nicolas; Mojallal, Ali; Damour, Odile; Vasson, Marie-Paule; Caldefie-Chezet, Florence

    2016-11-25

    Breast cancer is correlated with a higher risk of metastasis in obese postmenopausal women. Adipokines, whose plasma concentrations are modulated in obese subjects and adipocytes surround mammary cells, suggesting that adipocyte secretome affect mammary tumorogenesis. We hypothesize that mature adipocyte secretions from obese women conditioned or not by breast neoplasic cells, increase changes on the angiogenesis stages. Supernatants of human mature adipocytes, differentiated from stem cells of either adipose tissue of normal weight (MA20) or obese (MA30) women or obtained from co-cultures between MA20 and MA30 and breast cancer cell line MCF-7, were collected. The impact of these supernatants was investigated on proliferation, migration, and tube formation by endothelial cells (HUVEC). MA20 and MA30 showed a preservation of their "metabolic memory" (increase of Leptin, ObR, VEGF, CYP19A1, and a decrease of Adiponectin expression in MA30 compared to MA20). Supernatants from obese-adipocytes increased HUVEC proliferation, migration, and sprouting like with supernatants obtained from co-cultures of MA/MCF-7 regardless the women's BMI. Additional analyses such as the use of neutralizing antibodies, analysis of supernatants (Milliplex®) and variations in gene expression (qRT-PCR), strongly suggest an implication of IL-6, or a synergistic action among adipokines, probably associated with that of VEGF or IL-6. As a conclusion, supernatants from co-cultures of MA30 and MCF-7 cells increase proliferation, migration, and sprouting of HUVEC cells. These results provide insights into the interaction between adipocytes and epithelial cancer cells, particularly in case of obesity. The identification of synergistic action of adipokines would therefore be a great interest in developing preventive strategies. J. Cell. Physiol. 9999: 1-9, 2016. © 2016 Wiley Periodicals, Inc.

  4. Breast Cancer

    MedlinePlus

    ... version of this page please turn Javascript on. Breast Cancer What is Breast Cancer? How Tumors Form The body is made up ... tumors form in the breast tissue. Who Gets Breast Cancer? Breast cancer is one of the most common ...

  5. Cyclin A1 modulates the expression of vascular endothelial growth factor and promotes hormone-dependent growth and angiogenesis of breast cancer.

    PubMed

    Syed Khaja, Azharuddin Sajid; Dizeyi, Nishtman; Kopparapu, Pradeep Kumar; Anagnostaki, Lola; Härkönen, Pirkko; Persson, Jenny Liao

    2013-01-01

    Alterations in cellular pathways related to both endocrine and vascular endothelial growth factors (VEGF) may contribute to breast cancer progression. Inhibition of the elevated levels of these pathways is associated with clinical benefits. However, molecular mechanisms by which endocrine-related pathways and VEGF signalling cooperatively promote breast cancer progression remain poorly understood. In the present study, we show that the A-type cyclin, cyclin A1, known for its important role in the initiation of leukemia and prostate cancer metastasis, is highly expressed in primary breast cancer specimens and metastatic lesions, in contrasting to its barely detectable expression in normal human breast tissues. There is a statistically significant correlation between cyclin A1 and VEGF expression in breast cancer specimens from two patient cohorts (p<0.01). Induction of cyclin A1 overexpression in breast cancer cell line MCF-7 results in an enhanced invasiveness and a concomitant increase in VEGF expression. In addition, there is a formation of protein-protein complexes between cyclin A1 and estrogen receptor ER-α cyclin A1 overexpression increases ER-α expression in MCF-7 and T47D cells. In mouse tumor xenograft models in which mice were implanted with MCF-7 cells that overexpressed cyclin A1 or control vector, cyclin A1 overexpression results in an increase in tumor growth and angiogenesis, which is coincident with an enhanced expression of VEGF, VEGFR1 and ER-α Our findings unravel a novel role for cyclin A1 in growth and progression of breast cancer, and suggest that multiple cellular pathways, including cell cycle regulators, angiogenesis and estrogen receptor signalling, may cooperatively contribute to breast cancer progression.

  6. A class of extracellular vesicles from breast cancer cells activates VEGF receptors and tumour angiogenesis

    PubMed Central

    Feng, Qiyu; Zhang, Chengliang; Lum, David; Druso, Joseph E.; Blank, Bryant; Wilson, Kristin F.; Welm, Alana; Antonyak, Marc A.; Cerione, Richard A.

    2017-01-01

    Non-classical secretory vesicles, collectively referred to as extracellular vesicles (EVs), have been implicated in different aspects of cancer cell survival and metastasis. Here, we describe how a specific class of EVs, called microvesicles (MVs), activates VEGF receptors and tumour angiogenesis through a unique 90 kDa form of VEGF (VEGF90K). We show that VEGF90K is generated by the crosslinking of VEGF165, catalysed by the enzyme tissue transglutaminase, and associates with MVs through its interaction with the chaperone Hsp90. We further demonstrate that MV-associated VEGF90K has a weakened affinity for Bevacizumab, causing Bevacizumab to be ineffective in blocking MV-dependent VEGF receptor activation. However, treatment with an Hsp90 inhibitor releases VEGF90K from MVs, restoring the sensitivity of VEGF90K to Bevacizumab. These findings reveal a novel mechanism by which cancer cell-derived MVs influence the tumour microenvironment and highlight the importance of recognizing their unique properties when considering drug treatment strategies. PMID:28205552

  7. In vivo monitoring of angiogenesis inhibition via down-regulation of mir-21 in a VEGFR2-luc murine breast cancer model using bioluminescent imaging.

    PubMed

    Zhao, Dongliang; Tu, Yingfeng; Wan, Lin; Bu, Lihong; Huang, Tao; Sun, Xilin; Wang, Kai; Shen, Baozhong

    2013-01-01

    MicroRNA-21 (miR-21) is overexpressed in a wide range of cancers and involved in tumor proliferation and metastasis. However, the potential function of miR-21 in regulating tumor angiogenesis has been little disclosed. In this study, we treated the cultured 4T1 murine breast cancer cells and human umbilical vein endothelial cells (HUVECs) with miR-21 mimic, antagomir-21 or negative control (scramble), which were subjected to MTT, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), quantitative Reverse Transcriptase PCR (qRT-PCR) and immunoblotting analysis. In addition, 4T1 cells were implanted beneath the right breast fat pad of the VEGFR2-luc transgenic mice, which were randomly divided into three groups and received saline, antagomir-21 or scramble treatment once respectively after tumor model establishment. Bioluminescent imaging was used to monitor tumor growth and angiogenesis in vivo at 0d, 3d, 5d, 7d, 10d, and 14d after treatment. Mice were killed at the end of study and tumor tissues were collected for use. The results showed that knockdown of miR-21 by antagomir-21 decreased cell proliferation and induced apoptosis via targeting PTEN both in 4T1 cells and HUVECs. We also found the anti-angiogenesis and anti-tumor effects of antagomir-21 in the VEGFR2-luc transgenic mouse model using bioluminescent imaging. Moreover, the Western blotting data revealed that antagomir-21 inhibited tumor angiogenesis through suppressing HIF-1α/VEGF/VEGFR2-associated signaling pathway. In conclusion, the results from current study demonstrate that antagomir-21 can effectively suppress tumor growth and angiogenesis in VEGFR2-luc mouse breast tumor model and bioluminescent imaging can be used as a tool for noninvasively and continuously monitoring tumor angiogenesis in vivo.

  8. Localization of uPAR and MMP-9 in lipid rafts is critical for migration, invasion and angiogenesis in human breast cancer cells

    PubMed Central

    2010-01-01

    Background uPAR and MMP-9, which play critical roles in tumor cell invasion, migration and angiogenesis, have been shown to be associated with lipid rafts. Methods To investigate whether cholesterol could regulate uPAR and MMP-9 in breast carcinoma, we used MβCD (methyl beta cyclodextrin, which extracts cholesterol from lipid rafts) to disrupt lipid rafts and studied its effect on breast cancer cell migration, invasion, angiogenesis and signaling. Results Morphological evidence showed the association of uPAR with lipid rafts in breast carcinoma cells. MβCD treatment significantly reduced the colocalization of uPAR and MMP-9 with lipid raft markers and also significantly reduced uPAR and MMP-9 at both the protein and mRNA levels. Spheroid migration and invasion assays showed inhibition of breast carcinoma cell migration and invasion after MβCD treatment. In vitro angiogenesis studies showed a significant decrease in the angiogenic potential of cells pretreated with MβCD. MβCD treatment significantly reduced the levels of MMP-9 and uPAR in raft fractions of MDA-MB-231 and ZR 751 cells. Phosphorylated forms of Src, FAK, Cav, Akt and ERK were significantly inhibited upon MβCD treatment. Increased levels of soluble uPAR were observed upon MβCD treatment. Cholesterol supplementation restored uPAR expression to basal levels in breast carcinoma cell lines. Increased colocalization of uPAR with the lysosomal marker LAMP1 was observed in MβCD-treated cells when compared with untreated cells. Conclusion Taken together, our results suggest that cholesterol levels in lipid rafts are critical for the migration, invasion, and angiogenesis of breast carcinoma cells and could be a critical regulatory factor in these cancer cell processes mediated by uPAR and MMP-9. PMID:21106094

  9. Hexachlorobenzene promotes angiogenesis in vivo, in a breast cancer model and neovasculogenesis in vitro, in the human microvascular endothelial cell line HMEC-1.

    PubMed

    Pontillo, Carolina; Español, Alejandro; Chiappini, Florencia; Miret, Noelia; Cocca, Claudia; Alvarez, Laura; Kleiman de Pisarev, Diana; Sales, María Elena; Randi, Andrea Silvana

    2015-11-19

    Exposure to environmental pollutants may alter proangiogenic ability and promotes tumor growth. Hexachlorobenzene (HCB) is an organochlorine pesticide found in maternal milk and in lipid foods, and a weak ligand of the aryl hydrocarbon receptor (AhR). HCB induces migration and invasion in human breast cancer cells, as well as tumor growth and metastasis in vivo. In this study, we examined HCB action on angiogenesis in mammary carcinogenesis. HCB stimulates angiogenesis and increases vascular endothelial growth factor (VEGF) expression in a xenograft model with the human breast cancer cell line MDA-MB-231. Human microvascular endothelial cells HMEC-1 exposed to HCB (0.005, 0.05, 0.5 and 5μM) showed an increase in cyclooxygenase-2 (COX-2) and VEGF protein expression involving AhR. In addition, we found that HCB enhances VEGF-Receptor 2 (VEGFR2) expression, and activates its downstream pathways p38 and ERK1/2. HCB induces cell migration and neovasculogenesis in a dose-dependent manner. Cells pretreatment with AhR, COX-2 and VEGFR2 selective inhibitors, suppressed these effects. In conclusion, our results show that HCB promotes angiogenesis in vivo and in vitro. HCB-induced cell migration and tubulogenesis are mediated by AhR, COX-2 and VEGFR2 in HMEC-1. These findings may help to understand the association among HCB exposure, angiogenesis and mammary carcinogenesis.

  10. Therapeutic Electromagnetic Field (TEMF) and gamma irradiation on human breast cancer xenograft growth, angiogenesis and metastasis

    PubMed Central

    Cameron, Ivan L; Sun, Lu-Zhe; Short, Nicholas; Hardman, W Elaine; Williams, C Douglas

    2005-01-01

    Background The effects of a rectified semi-sinewave signal (15 mT amplitude, 120 pulses per second, EMF Therapeutics, Inc.) (TEMF) alone and in combination with gamma irradiation (IR) therapy in nude mice bearing a human MDA MB231 breast cancer xenograft were tested. Green fluorescence protein transfected cancer cells were injected into the mammary fat pad of young female mice. Six weeks later, mice were randomly divided into four treatment groups: untreated controls; 10 minute daily TEMF; 200 cGy of IR every other day (total 800 cGy); IR plus daily TEMF. Some mice in each group were euthanized 24 hours after the end of IR. TEMF treatment continued for 3 additional weeks. Tumor sections were stained for: endothelial cells with CD31 and PAS or hypoxia inducible factor 1α (HIF). Results Most tumors <35 mm3 were white but tumors >35 mm3 were pink and had a vascularized capsule. The cortex within 100 microns of the capsule had little vascularization. Blood vessels, capillaries, and endothelial pseudopods were found at >100 microns from the capsule (subcortex). Tumors >35 mm3 treated with IR 24 hours previously or with TEMF had decreased blood vessels in the subcortex and more endothelial pseudopods projecting into hypoxic, HIF positive areas than tumors from the control group. Mice that received either IR or TEMF had significantly fewer lung metastatic sites and slower tumor growth than did untreated mice. No harmful side effects were attributed to TEMF. Conclusion TEMF therapy provided a safe means for retarding tumor vascularization, growth and metastasis. PMID:16045802

  11. Glycolytic cancer associated fibroblasts promote breast cancer tumor growth, without a measurable increase in angiogenesis: evidence for stromal-epithelial metabolic coupling.

    PubMed

    Migneco, Gemma; Whitaker-Menezes, Diana; Chiavarina, Barbara; Castello-Cros, Remedios; Pavlides, Stephanos; Pestell, Richard G; Fatatis, Alessandro; Flomenberg, Neal; Tsirigos, Aristotelis; Howell, Anthony; Martinez-Outschoorn, Ubaldo E; Sotgia, Federica; Lisanti, Michael P

    2010-06-15

    Previously, we proposed a new model for understanding the Warburg effect in tumorigenesis and metastasis. In this model, the stromal fibroblasts would undergo aerobic glycolysis (a.k.a., the Warburg effect)--producing and secreting increased pyruvate/lactate that could then be used by adjacent epithelial cancer cells as "fuel" for the mitochondrial TCA cycle, oxidative phosphorylation, and ATP production. To test this model more directly, here we used a matched set of metabolically well-characterized immortalized fibroblasts that differ in a single gene. CL3 fibroblasts show a shift towards oxidative metabolism, and have an increased mitochondrial mass. In contrast, CL4 fibroblasts show a shift towards aerobic glycolysis, and have a reduced mitochondrial mass. We validated these differences in CL3 and CL4 fibroblasts by performing an unbiased proteomics analysis, showing the functional upregulation of 4 glycolytic enzymes, namely ENO1, ALDOA, LDHA and TPI1, in CL4 fibroblasts. Many of the proteins that were upregulated in CL4 fibroblasts, as seen by unbiased proteomics, were also transcriptionally upregulated in the stroma of human breast cancers, especially in the patients that were prone to metastasis. Importantly, when CL4 fibroblasts were co-injected with human breast cancer cells (MDA-MB-231) in a xenograft model, tumor growth was dramatically enhanced. CL4 fibroblasts induced a > 4-fold increase in tumor mass, and a near 8-fold increase in tumor volume, without any measurable increases in tumor angiogenesis. In parallel, CL3 and CL4 fibroblasts both failed to form tumors when they were injected alone, without epithelial cancer cells. Mechanistically, under co-culture conditions, CL4 glycolytic fibroblasts increased mitochondrial activity in adjacent breast cancer cells (relative to CL3 cells), consistent with the "Reverse Warburg Effect". Notably, Western blot analysis of CL4 fibroblasts revealed a significant reduction in caveolin-1 (Cav-1) protein levels

  12. Targeting COX-2 and EP4 to control tumor growth, angiogenesis, lymphangiogenesis and metastasis to the lungs and lymph nodes in a breast cancer model.

    PubMed

    Xin, Xiping; Majumder, Mousumi; Girish, Gannareddy V; Mohindra, Vik; Maruyama, Takayuki; Lala, Peeyush K

    2012-08-01

    We reported that cyclo-oxygenase (COX)-2 expression in human breast cancer stimulated cancer cell migration and invasiveness, production of vascular endothelial growth factor (VEGF)-C and lymphangiogenesis in situ, largely from endogenous PGE2-mediated stimulation of prostaglandin E (EP)1 and EP4 receptors, presenting them as candidate therapeutic targets against lymphatic metastasis. As human breast cancer xenografts in immuno-compromised mice have limitations for preclinical testing, we developed a syngeneic murine breast cancer model of spontaneous lymphatic metastasis mimicking human and applied it for mechanistic and therapeutic studies. We tested the roles of COX-2 and EP receptors in VEGF-C and -D production by a highly metastatic COX-2 expressing murine breast cancer cell line C3L5. These cells expressed all EP receptors and produced VEGF-C and -D, both inhibited with COX-2 inhibitors or EP4 (but not EP1, EP2 or EP3) antagonists. C3H/HeJ mice, when implanted SC in both inguinal regions with C3L5 cells suspended in growth factor-reduced Matrigel, exhibited rapid tumor growth, tumor-associated angiogenesis and lymphangiogenesis (respectively measured with CD31 and LYVE-1 immunostaining), metastasis to the inguinal and axillary lymph nodes and the lungs. Chronic oral administration of COX-1/COX-2 inhibitor indomethacin, COX-2 inhibitor celecoxib and an EP4 antagonist ONO-AE3-208, but not an EP1 antagonist ONO-8713 at nontoxic doses markedly reduced tumor growth, lymphangiogenesis, angiogenesis, and metastasis to lymph nodes and lungs. Residual tumors in responding mice revealed reduced VEGF-C and -D proteins, AkT phosphorylation and increased apoptotic/proliferative cell ratios consistent with blockade of EP4 signaling. We suggest that EP4 antagonists deserve clinical testing for chemo-intervention of lymphatic metastasis in human breast cancer.

  13. Mesenchymal Stem Cells for Vascular Target Discovery in Breast Cancer-Associated Angiogenesis

    DTIC Science & Technology

    2004-09-01

    inadequacy of CD34 expression as a universal surrogate marker for stem cells capable of vascular regeneration and caution must be exercised in cell...factors. From this we identified four growth factors (FGF7, HDGF, NGFb, and BDNF ) which can influence angiogenesis.(19-27) In particular, FGF7 and HDGF are...Madri JA. Paracrine and Autocrine Functions of Brain-derived Neurotrophic Factor ( BDNF ) and Nerve Growth Factor (NGF) in Brain-derived Endothelial Cells

  14. Mesenchymal Stem Cells for Vascular Target Discovery in Breast Cancer-Associated Angiogenesis

    DTIC Science & Technology

    2005-09-01

    highlights the inadequacy of CD34 expression as a universal surrogate marker for stem cells capable of vascular regeneration and caution must be exercised ...ability to act as angiogenic factors. From this we identified four growth factors (FGF7, HDGF, NGFb, and BDNF ) which can influence angiogenesis.(19-27) In...2002; 16(10): 1307-1309. (25) Kim H, Li Q, Hempstead BL, Madri JA. Paracrine and Autocrine Functions of Brain-derived Neurotrophic Factor ( BDNF ) and

  15. Evaluation of Curcumin Capped Copper Nanoparticles as Possible Inhibitors of Human Breast Cancer Cells and Angiogenesis: a Comparative Study with Native Curcumin.

    PubMed

    Kamble, Sonali; Utage, Bhimashankar; Mogle, Pratima; Kamble, Rahul; Hese, Shrikant; Dawane, Bhaskar; Gacche, Rajesh

    2016-10-01

    Synthesis of metal nanoparticles for improving therapeutic index and drug delivery is coming up as an attractive strategy in the mainstream of cancer therapeutic research. In the present study, curcumin-capped copper nanoparticles (CU-NPs) were evaluated as possible inhibitors of in vivo angiogenesis, pro-angiogenic cytokines involved in promoting tumor angiogenesis along with inhibition of cell proliferation and migration of breast cancer cell line MDA-MB-231. The antiangiogenic potential was assessed using in vivo chorioallantoic membrane (CAM) model. 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT)-based cytotoxicity assay was used to assess the effect of CU-NPs against proliferation of breast cancer cell line. The wound healing migration assay was used to evaluate the effects of CU-NPs on the migration ability of breast cancer cell line. Native curcumin (CU) was used as a reference compound for comparison purpose. The result of the present investigation indicates that CU-NPs could not demonstrate impressive antiangiogenic or anticancer activities significantly as compared to native CU. The possible mechanisms of experimental outcomes are discussed in the light of the methods of nanoparticle synthesis in concert with the current state of the art literature.

  16. Gold nanoparticle-conjugated quercetin inhibits epithelial-mesenchymal transition, angiogenesis and invasiveness via EGFR/VEGFR-2-mediated pathway in breast cancer.

    PubMed

    Balakrishnan, S; Bhat, F A; Raja Singh, P; Mukherjee, S; Elumalai, P; Das, S; Patra, C R; Arunakaran, J

    2016-12-01

    Epidermal growth factor plays a critical role in breast malignancies by enhancing cell proliferation, invasion, angiogenesis and metastasis. Epithelial-mesenchymal transition (EMT) is a crucial process by which epithelial cells lose polarity and acquire migratory mesenchymal properties. Gold nanoparticles are an efficient drug delivery vehicle for carrying chemotherapeutic agents to target cancer cells and quercetin is an anti-oxidative flavonoid known with potent anti-malignant cell activity. Cell viability was assessed by MTT assay, and protein expression was examined by Western blotting and immunocytochemistry. Cell invasion was monitored using invasion chambers, and cell migration was analysed by scratch wound-healing assay. In vitro and ex vivo angiogenesis studies were performed by capillary-like tube formation assay and chick embryo angiogenesis assay (CEA). 7,12-dimethylbenz(a)anthracene (DMBA) induced mammary carcinoma in Sprague-Dawley rats. We observed a significant reduction in protein expression of vimentin, N-cadherin, Snail, Slug, Twist, MMP-2, MMP-9, p-EGFR, VEGFR-2, p-PI3K, Akt and p-GSK3β, and enhanced E-cadherin protein expression in response to AuNPs-Qu-5 treatment. AuNPs-Qu-5 inhibited migration and invasion of MCF-7 and MDA-MB-231 cells compared to free quercetin. AuNPs-Qu-5-treated HUVECs had reduced cell viability and capillary-like tube formation. In vitro and in vivo angiogenesis assays showed that AuNPs-Qu-5 suppressed tube and new blood vessel formation. Treatment with AuNPs-Qu-5 impeded tumour growth in DMBA-induced mammary carcinoma in SD rats compared to treatment with free quercetin. Our results suggest that AuNPs-Qu-5 inhibited EMT, angiogenesis and metastasis of the breast cancer cells tested by targeting the EGFR/VEGFR-2 signalling pathway. © 2016 John Wiley & Sons Ltd.

  17. The Use of Novel PET Tracers to Image Breast Cancer Biologic Processes Such as Proliferation, DNA Damage and Repair, and Angiogenesis.

    PubMed

    Kenny, Laura

    2016-02-01

    The balance between proliferation and cell death is pivotal to breast tumor growth. Because of a combination of environmental and genetic factors leading to activation of oncogenes or inactivation of tumor suppressor genes, these processes become deregulated in cancer. PET imaging of proliferation, angiogenesis, and DNA damage and repair offers the opportunity to monitor therapeutic efficacy to detect changes in tumor biology that may precede physical size reduction and simultaneously allows the study of intratumoral and intertumoral heterogeneity.This review examines recent developments in breast cancer imaging using novel probes. The probes discussed here are not licensed for routine use and are at various stages of development ranging from preclinical development (e.g., the DNA repair marker γH2AX) to clinical validation in larger studies (such as the proliferation probe 3'-deoxy-3'-(18)F-fluorothymidine [(18)F-FLT]). In breast cancer, most studies have focused on proliferation imaging mainly based on (18)F-labeled thymidine analogs. Initial studies have been promising; however, the results of larger validation studies are necessary before being incorporated into routine clinical use. Although there are distinct advantages in using process-specific probes, properties such as metabolism need careful consideration, because high background uptake in the liver due to glucuronidation in the case of (18)F-FLT may limit utility for imaging of liver metastases.Targeting angiogenesis has had some success in tumors such as renal cell carcinoma; however, angiogenesis inhibitors have not been particularly successful in the clinical treatment of breast cancer. This could be potentially attributed to patient selection due to the lack of validated predictive and responsive biomarkers; the quest for a successful noninvasive biomarker for angiogenesis could solve this challenge. Finally, we look at cell death including apoptosis and DNA damage and repair probes, the most well

  18. Captopril-polyethyleneimine conjugate modified gold nanoparticles for co-delivery of drug and gene in anti-angiogenesis breast cancer therapy.

    PubMed

    Li, Manhong; Li, Yong; Huang, Xiaohui; Lu, Xizhi

    2015-01-01

    Captopril-polyethyleneimine (CP) containing low molecular weight polyethyleneimine and anti-angiogenesis drug captopril conjugated via an amide bond was fabricated to modify gold nanoparticles and complex with siRNA to construct siRNA/CP/GNP complexes for the co-delivery of drug and siRNA in anti-angiogenesis breast cancer therapy. The self-assembled siRNA/CP/GNP complexes exhibited desirable and homogenous particle size, reasonable positive charges and condensation ability, and effective gene-silencing property in vitro. In addition, siRNA/CP/GNP complexes co-delivering captopril and siRNA achieved combined angiogenesis suppression by more effectively downregulating the expression of vascular endothelial growth factor mRNA and protein via different pathways in vitro, as compared to mono-delivery systems. In vivo investigation on nude mice bearing MDA-MB435 tumor xenografts revealed that siRNA/CP/GNP complexes possessed satisfying tumor homing ability and strong antitumor activity. These findings suggested that siRNA/CP/GNP complexes could be an ideal system for simultaneous transfer of drug and siRNA, which might be a new promising strategy for effective breast cancer therapy.

  19. SCFJFK is a bona fide E3 ligase for ING4 and a potent promoter of the angiogenesis and metastasis of breast cancer

    PubMed Central

    Yan, Ruorong; He, Lin; Li, Zhongwu; Han, Xiao; Liang, Jing; Si, Wenzhe; Chen, Zhe; Li, Lei; Xie, Guojia; Li, Wanjin; Wang, Peiyan; Lei, Liandi; Zhang, Hongquan; Pei, Fei; Cao, Dengfeng

    2015-01-01

    Loss of function/dysregulation of inhibitor of growth 4 (ING4) and hyperactivation of NF-κB are frequent events in many types of human malignancies. However, the molecular mechanisms underlying these remarkable aberrations are not understood. Here, we report that ING4 is physically associated with JFK. We demonstrated that JFK targets ING4 for ubiquitination and degradation through assembly of an Skp1–Cul1–F-box (SCF) complex. We showed that JFK-mediated ING4 destabilization leads to the hyperactivation of the canonical NF-κB pathway and promotes angiogenesis and metastasis of breast cancer. Significantly, the expression of JFK is markedly up-regulated in breast cancer, and the level of JFK is negatively correlated with that of ING4 and positively correlated with an aggressive clinical behavior of breast carcinomas. Our study identified SCFJFK as a bona fide E3 ligase for ING4 and unraveled the JFK–ING4–NF-κB axis as an important player in the development and progression of breast cancer, supporting the pursuit of JFK as a potential target for breast cancer intervention. PMID:25792601

  20. SCF(JFK) is a bona fide E3 ligase for ING4 and a potent promoter of the angiogenesis and metastasis of breast cancer.

    PubMed

    Yan, Ruorong; He, Lin; Li, Zhongwu; Han, Xiao; Liang, Jing; Si, Wenzhe; Chen, Zhe; Li, Lei; Xie, Guojia; Li, Wanjin; Wang, Peiyan; Lei, Liandi; Zhang, Hongquan; Pei, Fei; Cao, Dengfeng; Sun, Luyang; Shang, Yongfeng

    2015-03-15

    Loss of function/dysregulation of inhibitor of growth 4 (ING4) and hyperactivation of NF-κB are frequent events in many types of human malignancies. However, the molecular mechanisms underlying these remarkable aberrations are not understood. Here, we report that ING4 is physically associated with JFK. We demonstrated that JFK targets ING4 for ubiquitination and degradation through assembly of an Skp1-Cul1-F-box (SCF) complex. We showed that JFK-mediated ING4 destabilization leads to the hyperactivation of the canonical NF-κB pathway and promotes angiogenesis and metastasis of breast cancer. Significantly, the expression of JFK is markedly up-regulated in breast cancer, and the level of JFK is negatively correlated with that of ING4 and positively correlated with an aggressive clinical behavior of breast carcinomas. Our study identified SCF(JFK) as a bona fide E3 ligase for ING4 and unraveled the JFK-ING4-NF-κB axis as an important player in the development and progression of breast cancer, supporting the pursuit of JFK as a potential target for breast cancer intervention. © 2015 Yan et al.; Published by Cold Spring Harbor Laboratory Press.

  1. Natural products against cancer angiogenesis.

    PubMed

    Khalid, El Bairi; Ayman, El-Meghawry El-Kenawy; Rahman, Heshu; Abdelkarim, Guaadaoui; Najda, Agnieszka

    2016-11-01

    The process of angiogenesis is quite well-known nowadays. Some medicines and extracts affecting this process are already used routinely in supporting the conventional treatment of many diseases that are considered angiogenic such as cancer. However, we must be aware that the area of currently used drugs of this type is much narrower than the theoretical possibilities existing in therapeutic angiogenesis. Plant substances are a large and diverse group of compounds that are found naturally in fruits, vegetables, spices, and medicinal plants. They also have different anticancer properties. The aim of this literature review article is to present the current state of knowledge concerning the molecular targets of tumor angiogenesis and the active substances (polyphenols, alkaloids, phytohormones, carbohydrates, and terpenes) derived from natural sources, whose activity against cancer angiogenesis has been confirmed.

  2. Nef-M1, a peptide antagonist of CXCR4, inhibits tumor angiogenesis and epithelial‑to‑mesenchymal transition in colon and breast cancers.

    PubMed

    Katkoori, Venkat R; Basson, Marc D; Bond, Vincent C; Manne, Upender; Bumpers, Harvey L

    2015-09-29

    The Nef-M1 peptide competes effectively with the natural ligand of CXC chemokine receptor 4 (CXCR4), stromal cell-derived factor 1-alpha, to induce apoptosis and inhibit growth in colon cancer (CRC) and breast cancer (BC). Its role in tumor angiogenesis, and epithelial-to-mesenchymal transition (EMT) regulation, key steps involved in tumor growth and metastasis, are unknown. We evaluated the angioinhibitory effect of Nef-M1 peptide and examined its role in the inhibition of EMT in these cancers. Colon (HT29) and breast (MDA-MB231) cancer cells expressing CXCR4 were studied in vitro and in xenograft tumors propagated in severe combined immunodeficient mice. The mice were treated intraperitoneally with Nef-M1 or scrambled amino acid sequence of Nef-M1 (sNef-M1) peptide, a negative control, starting at the time of tumor implantation. Sections from tumors were evaluated for tumor angiogenesis, as measured by microvessel density (MVD) based on immunostaining of endothelial markers. In vitro tumor angiogenesis was assessed by treating human umbilical vein endothelial cells with conditioned media from the tumor cell lines. A BC cell line (MDA-MB 468) which does not express CXCR4 was used to study the actions of Nef-M1 peptide. Western blot and immunofluorescence analyses assessed the effect of Nef-M1 on tumor angiogenesis and EMT in both tumors and cancer cells. Metastatic lesions of CRC and BC expressed more CXCR4 than primary lesions. It was also found that tumors from mice treated with sNef-M1 had well established vascularity, while Nef-M1 treated tumors had very poor vascularization. Indeed, the mean MVD was lower in tumors from Nef-M1 treated mice than in sNef-M1 treated tumors. Nef-M1 treated tumor has poor morphology and loss of endothelial integrity. Although conditioned medium from CRC or BC cells supported HUVEC tube formation, the conditioned medium from Nef-M1 treated CRC or BC cells did not support tube formation. Western blot analyses revealed that Nef-M1

  3. Complementary populations of human adipose CD34+ progenitor cells promote growth, angiogenesis, and metastasis of breast cancer.

    PubMed

    Orecchioni, Stefania; Gregato, Giuliana; Martin-Padura, Ines; Reggiani, Francesca; Braidotti, Paola; Mancuso, Patrizia; Calleri, Angelica; Quarna, Jessica; Marighetti, Paola; Aldeni, Chiara; Pruneri, Giancarlo; Martella, Stefano; Manconi, Andrea; Petit, Jean-Yves; Rietjens, Mario; Bertolini, Francesco

    2013-10-01

    Obesity is associated with an increased frequency, morbidity, and mortality of several types of neoplastic diseases, including postmenopausal breast cancer. We found that human adipose tissue contains two populations of progenitors with cooperative roles in breast cancer. CD45(-)CD34(+)CD31(+)CD13(-)CCRL2(+) endothelial cells can generate mature endothelial cells and capillaries. Their cancer-promoting effect in the breast was limited in the absence of CD45(-)CD34(+)CD31(-)CD13(+)CD140b(+) mesenchymal progenitors/adipose stromal cells (ASC), which generated pericytes and were more efficient than endothelial cells in promoting local tumor growth. Both endothelial cells and ASCs induced epithelial-to-mesenchymal transition (EMT) gene expression in luminal breast cancer cells. Endothelial cells (but not ASCs) migrated to lymph nodes and to contralateral nascent breast cancer lesions where they generated new vessels. In vitro and in vivo, endothelial cells were more efficient than ASCs in promoting tumor migration and in inducing metastases. Granulocyte colony-stimulating factor (G-CSF) effectively mobilized endothelial cells (but not ASCs), and the addition of chemotherapy and/or of CXCR4 inhibitors did not increase endothelial cell or ASC blood mobilization. Our findings suggest that adipose tissue progenitor cells cooperate in driving progression and metastatic spread of breast cancer.

  4. What Is Breast Cancer?

    MedlinePlus

    ... 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 ...

  5. The ROS-mediated activation of STAT-3/VEGF signaling is involved in the 27-hydroxycholesterol-induced angiogenesis in human breast cancer cells.

    PubMed

    Zhu, Dongmei; Shen, Zhaoxia; Liu, Jiao; Chen, Juan; Liu, Yun; Hu, Chunyan; Li, Zhong; Li, Yuan

    2016-12-15

    Breast cancer (BC) is the leading cause of cancer-related mortality among females worldwide, and angiogenesis plays a crucial role in BC progression. 27-Hydroxycholesterol (27HC) is an endogenous selective estrogen receptor modulator, which promotes the growth and metastasis of BC. Here, we further found that, 27HC improved the angiogenic ability of BC in a VEGF-dependent manner. For the molecular mechanisms, on one hand, as an estrogen-like factor, 27HC enhanced the expression of VEGF by the classical ERα/VEGF signaling in ER-positive BC cells; on the other hand, in both ER-positive and ER-negative BC cells, 27HC enhanced the generation of ROS, which in turn activated the STAT-3/VEGF signaling in an ER independent manner. Either blocking the generation of ROS or knockdown of STAT-3 attenuated the 27HC-induced autocrine of VEGF and angiogenesis. These findings not only suggested a mechanism whereby 27HC enhanced the angiogenesis, but also helped to recognize the 27HC as a novel potential harmful factor in BC, especially in the menopause patients.

  6. Breast tumor angiogenesis analysis using 3D power Doppler ultrasound

    NASA Astrophysics Data System (ADS)

    Chang, Ruey-Feng; Huang, Sheng-Fang; Lee, Yu-Hau; Chen, Dar-Ren; Moon, Woo Kyung

    2006-03-01

    Angiogenesis is the process that correlates to tumor growth, invasion, and metastasis. Breast cancer angiogenesis has been the most extensively studied and now serves as a paradigm for understanding the biology of angiogenesis and its effects on tumor outcome and patient prognosis. Most studies on characterization of angiogenesis focus on pixel/voxel counts more than morphological analysis. Nevertheless, in cancer, the blood flow is greatly affected by the morphological changes, such as the number of vessels, branching pattern, length, and diameter. This paper presents a computer-aided diagnostic (CAD) system that can quantify vascular morphology using 3-D power Doppler ultrasound (US) on breast tumors. We propose a scheme to extract the morphological information from angiography and to relate them to tumor diagnosis outcome. At first, a 3-D thinning algorithm helps narrow down the vessels into their skeletons. The measurements of vascular morphology significantly rely on the traversing of the vascular trees produced from skeletons. Our study of 3-D assessment of vascular morphological features regards vessel count, length, bifurcation, and diameter of vessels. Investigations into 221 solid breast tumors including 110 benign and 111 malignant cases, the p values using the Student's t-test for all features are less than 0.05 indicating that the proposed features are deemed statistically significant. Our scheme focuses on the vascular architecture without involving the technique of tumor segmentation. The results show that the proposed method is feasible, and have a good agreement with the diagnosis of the pathologists.

  7. Breast Cancer

    MedlinePlus

    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 ... age 35, and having dense breasts. Symptoms of breast cancer may include a lump in the breast, a ...

  8. The novel desmopressin analogue [V4Q5]dDAVP inhibits angiogenesis, tumour growth and metastases in vasopressin type 2 receptor-expressing breast cancer models

    PubMed Central

    GARONA, JUAN; PIFANO, MARINA; ORLANDO, ULISES D.; PASTRIAN, MARIA B.; IANNUCCI, NANCY B.; ORTEGA, HUGO H.; PODESTA, ERNESTO J.; GOMEZ, DANIEL E.; RIPOLL, GISELLE V.; ALONSO, DANIEL F.

    2015-01-01

    Desmopressin (dDAVP) is a safe haemostatic agent with previously reported antitumour activity. It acts as a selective agonist for the V2 vasopressin membrane receptor (V2r) present on tumour cells and microvasculature. The purpose of this study was to evaluate the novel peptide derivative [V4Q5]dDAVP in V2r-expressing preclinical mouse models of breast cancer. We assessed antitumour effects of [V4Q5]dDAVP using human MCF-7 and MDA-MB-231 breast carcinoma cells, as well as the highly metastatic mouse F3II cell line. Effect on in vitro cancer cell growth was evaluated by cell proliferation and clonogenic assays. Cell cycle distribution was analysed by flow cytometry. In order to study the effect of intravenously administered [V4Q5]dDAVP on tumour growth and angiogenesis, breast cancer xenografts were generated in athymic mice. F3II cells were injected into syngeneic mice to evaluate the effect of [V4Q5]dDAVP on spontaneous and experimental metastatic spread. In vitro cytostatic effects of [V4Q5]dDAVP against breast cancer cells were greater than those of dDAVP, and associated with V2r-activated signal transduction and partial cell cycle arrest. In MDA-MB-231 xenografts, [V4Q5]dDAVP (0.3 μg/kg, thrice a week) reduced tumour growth and angiogenesis. Treatment of F3II mammary tumour-bearing immunocompetent mice resulted in complete inhibition of metastatic progression. [V4Q5]dDAVP also displayed greater antimetastatic efficacy than dDAVP on experimental lung colonisation by F3II cells. The novel analogue was well tolerated in preliminary acute toxicology studies, at doses ≥300-fold above that required for anti-angiogenic/antimetastatic effects. Our data establish the preclinical activity of [V4Q5]dDAVP in aggressive breast cancer, providing the rationale for further clinical trials. PMID:25846632

  9. Breast cancer

    MedlinePlus

    ... idea of what to expect in the future. Breast cancer stages range from 0 to IV. The higher the ... is based on many factors, including: Type of breast cancer Stage of the cancer (staging is a tool your ...

  10. Multi-modal Imaging of Angiogenesis in a Nude Rat Model of Breast Cancer Bone Metastasis Using Magnetic Resonance Imaging, Volumetric Computed Tomography and Ultrasound

    PubMed Central

    Bäuerle, Tobias; Komljenovic, Dorde; Berger, Martin R.; Semmler, Wolfhard

    2012-01-01

    Angiogenesis is an essential feature of cancer growth and metastasis formation. In bone metastasis, angiogenic factors are pivotal for tumor cell proliferation in the bone marrow cavity as well as for interaction of tumor and bone cells resulting in local bone destruction. Our aim was to develop a model of experimental bone metastasis that allows in vivo assessment of angiogenesis in skeletal lesions using non-invasive imaging techniques. For this purpose, we injected 105 MDA-MB-231 human breast cancer cells into the superficial epigastric artery, which precludes the growth of metastases in body areas other than the respective hind leg1. Following 25-30 days after tumor cell inoculation, site-specific bone metastases develop, restricted to the distal femur, proximal tibia and proximal fibula1. Morphological and functional aspects of angiogenesis can be investigated longitudinally in bone metastases using magnetic resonance imaging (MRI), volumetric computed tomography (VCT) and ultrasound (US). MRI displays morphologic information on the soft tissue part of bone metastases that is initially confined to the bone marrow cavity and subsequently exceeds cortical bone while progressing. Using dynamic contrast-enhanced MRI (DCE-MRI) functional data including regional blood volume, perfusion and vessel permeability can be obtained and quantified2-4. Bone destruction is captured in high resolution using morphological VCT imaging. Complementary to MRI findings, osteolytic lesions can be located adjacent to sites of intramedullary tumor growth. After contrast agent application, VCT angiography reveals the macrovessel architecture in bone metastases in high resolution, and DCE-VCT enables insight in the microcirculation of these lesions5,6. US is applicable to assess morphological and functional features from skeletal lesions due to local osteolysis of cortical bone. Using B-mode and Doppler techniques, structure and perfusion of the soft tissue metastases can be evaluated

  11. Nelumbo nucifera Gaertn leaves extract inhibits the angiogenesis and metastasis of breast cancer cells by downregulation connective tissue growth factor (CTGF) mediated PI3K/AKT/ERK signaling.

    PubMed

    Chang, Chun-Hua; Ou, Ting-Tsz; Yang, Mon-Yuan; Huang, Chi-Chou; Wang, Chau-Jong

    2016-07-21

    Nelumbo nucifera Gaertn (Nymphaeaceae) has been recognized as a medicinal plant, which was distributed throughout the Asia. The aqueous extract of Nelumbo nucifera leaves extract (NLE) has various biologically active components such as polyphenols, flavonoids, oligomeric procyanidines. However, the role of NLE in breast cancer therapy is poorly understood. The purpose of this study was to identify the hypothesis that NLE can suppress tumor angiogenesis and metastasis through CTGF (connective tissue growth factor), which has been implicated in tumor angiogenesis and progression in breast cancer MDA-MB-231 cells. We examined the effects of NLE on angiogenesis in the chicken chorioallantoic membrane (CAM) model. The data showed that NLE could reduce the chorionic plexus at day 17 in CAM and the duration of this inhibition was dose-dependent. In Xenograft model, NLE treatment significantly reduced tumor weight and CD31 (capillary density) over control, respectively. We examined the role of angiogenesis involved restructuring of endothelium using human umbilical vein endothelial cell (HUVEC) in Matrigel angiogenesis model. The results indicated that vascular-like structure formation was further blocked by NLE treatment. Moreover, knockdown of CTGF expression markedly reduced the expression of MMP2 as well as VEGF, and attenuated PI3K-AKT-ERK activation, indication that these signaling pathways are crucial in mediating CTGF function. The present results suggest that NLE might be useful for treatment in therapy-resistance triple negative breast cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Overexpression of angiotensin II type 1 receptor in breast cancer cells induces epithelial-mesenchymal transition and promotes tumor growth and angiogenesis.

    PubMed

    Oh, Eunhye; Kim, Ji Young; Cho, Youngkwan; An, Hyunsook; Lee, Nahyun; Jo, Hunho; Ban, Changill; Seo, Jae Hong

    2016-06-01

    The angiotensin II type I receptor (AGTR1) has been implicated in diverse aspects of human disease, from the regulation of blood pressure and cardiovascular homeostasis to cancer progression. We sought to investigate the role of AGTR1 in cell proliferation, epithelial-mesenchymal transition (EMT), migration, invasion, angiogenesis and tumor growth in the breast cancer cell line MCF7. Stable overexpression of AGTR1 was associated with accelerated cell proliferation, concomitant with increased expression of survival factors including poly(ADP-ribose) polymerase (PARP) and X-linked inhibitor of apoptosis (XIAP), as well as extracellular signal-regulated kinase (ERK) activation. AGTR1-overexpressing MCF7 cells were more aggressive than their parent line, with significantly increased activity in migration and invasion assays. These observations were associated with changes in EMT markers, including reduced E-cadherin expression and increased p-Smad3, Smad4 and Snail levels. Treatment with the AGTR1 antagonist losartan attenuated these effects. AGTR1 overexpression also accelerated tumor growth and increased Ki-67 expression in a xenograft model. This was associated with increased tumor angiogenesis, as evidenced by a significant increase in microvessels in the intratumoral and peritumoral areas, and enhanced tumor invasion, with the latter response associated with increased EMT marker expression and matrix metallopeptidase 9 (MMP-9) upregulation. In vivo administration of losartan significantly reduced both tumor growth and angiogenesis. Our findings suggest that AGTR1 plays a significant role in tumor aggressiveness, and its inhibition may have therapeutic implications. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Rhus coriaria suppresses angiogenesis, metastasis and tumor growth of breast cancer through inhibition of STAT3, NFκB and nitric oxide pathways

    PubMed Central

    El Hasasna, Hussain; Saleh, Alaaeldin; Samri, Halima Al; Athamneh, Khawlah; Attoub, Samir; Arafat, Kholoud; Benhalilou, Nehla; Alyan, Sofyan; Viallet, Jean; Dhaheri, Yusra Al; Eid, Ali; Iratni, Rabah

    2016-01-01

    Recently, we reported that Rhus coriaria exhibits anticancer activities by promoting cell cycle arrest and autophagic cell death of the metastatic triple negative MDA-MB-231 breast cancer cells. Here, we investigated the effect of Rhus coriaria on the migration, invasion, metastasis and tumor growth of TNBC cells. Our current study revealed that non-cytotoxic concentrations of Rhus coriaria significantly inhibited migration and invasion, blocked adhesion to fibronectin and downregulated MMP-9 and prostaglandin E2 (PgE2). Not only did Rhus coriaria decrease their adhesion to HUVECs and to lung microvascular endothelial (HMVEC-L) cells, but it also inhibited the transendothelial migration of MDA-MB-231 cells through TNF-α-activated HUVECs. Furthermore, we found that Rhus coriaria inhibited angiogenesis, reduced VEGF production in both MDA-MB-231 and HUVECs and downregulated the inflammatory cytokines TNF-α, IL-6 and IL-8. The underlying mechanism for Rhus coriaria effects appears to be through inhibiting NFκB, STAT3 and nitric oxide (NO) pathways. Most importantly, by using chick embryo tumor growth assay, we showed that Rhus coriaria suppressed tumor growth and metastasis in vivo. The results described in the present study identify Rhus coriaria as a promising chemopreventive and therapeutic candidate that modulate triple negative breast cancer growth and metastasis. PMID:26888313

  14. Activation of GPER suppresses migration and angiogenesis of triple negative breast cancer via inhibition of NF-κB/IL-6 signals.

    PubMed

    Liang, Shuwei; Chen, Zhuojia; Jiang, Guanmin; Zhou, Yan; Liu, Qiao; Su, Qiao; Wei, Weidong; Du, Jun; Wang, Hongsheng

    2017-02-01

    Triple-negative breast cancer (TNBC) is characterized by high vascularity and frequent metastasis. Here, we found that activation of G protein-coupled estrogen receptor (GPER) by its specific agonist G-1 can significantly inhibit interleukin 6 (IL-6) and vascular endothelial growth factor A (VEGF-A). TNBC tissue microarrays from 100 TNBC patients revealed GPER is negatively associated with IL-6 levels and higher grade and stage. Activation of GPER or anti-IL-6 antibody can inhibit both in vitro tube formation of human umbilical vein endothelial cells (HUVECs) and migration of TNBC cells. While recombinant IL-6 supplementary can significantly reverse the inhibitory effects of G-1, suggesting the essential role of IL-6 in G-1 induced suppression of angiogenesis and invasiveness of TNBC cells. G-1 treatment decreased the phosphorylation, nuclear localization, transcriptional activities of NF-κB and suppressed its binding with IL-6 promoter. BAY11-7028, the inhibitor of NF-κB, can mimic the effect of G-1 to suppression of IL-6 and VEGF-A. While over expression of p65 can attenuate the inhibitory effects of G-1 on IL-6 and VEGF expression. The suppression of IL-6 by G-1 can further inhibit HIF-1α and STAT3 signals in TNBC cells by inhibition their expression, phosphorylation and/or nuclear localization. Moreover, G-1 also inhibited the in vivo NF-κB/IL-6 signals and angiogenesis and metastasis of MDA-MB-231 xenograft tumors. In conclusion, our study demonstrated that activation of GPER can suppress migration and angiogenesis of TNBC via inhibition of NF-κB/IL-6 signals, therefore it maybe act as an important target for TNBC treatment.

  15. Angiogenesis: a prognostic determinant in pancreatic cancer?

    PubMed

    van der Zee, Jill A; van Eijck, Casper H J; Hop, Wim C J; van Dekken, Herman; Dicheva, Bilyana M; Seynhaeve, Ann L B; Koning, Gerben A; Eggermont, Alexander M M; ten Hagen, Timo L M

    2011-11-01

    Angiogenesis has been associated with disease progression in many solid tumours, however the statement that tumours need angiogenesis to grow, invade and metastasise seems no longer applicable to all tumours or to all tumour subtypes. Prognostic studies in pancreatic cancer are conflicting. In fact, pancreatic cancer has been suggested an example of a tumour in which angiogenesis is less essential for tumour progression. The aim of the present study was therefore to measure angiogenesis in two anatomically closely related however prognostically different types of pancreatic cancer, pancreatic head and periampullary cancer, and investigate its relation with outcome. Vessels were stained by CD31 on original paraffin embedded tissue from 206 patients with microscopic radical resection (R0) of pancreatic head (n=98) or periampullary cancer (n=108). Angiogenesis was quantified by microvessel density (MVD) and measured by computerised image analysis of three randomly selected fields and investigated for associations with recurrence free survival (RFS), cancer specific survival (CSS), overall survival (OS) and conventional prognostic factors. MVD was heterogeneous both between and within tumours. A higher MVD was observed in periampullary cancers compared with pancreatic head cancers (p<.01). Furthermore, MVD was associated with lymph node involvement in pancreatic head (p=.014), but not in periampullary cancer (p=.55). Interestingly, MVD was not associated with RFS, CSS or with OS. In conclusion, angiogenesis is higher in periampullary cancer and although associated with nodal involvement in pancreatic head cancer, pancreatic cancer prognosis seems indeed angiogenesis independent.

  16. Interface between breast cancer cells and the tumor microenvironment using platelet-rich plasma to promote tumor angiogenesis - influence of platelets and fibrin bundles on the behavior of breast tumor cells.

    PubMed

    Andrade, Sheila Siqueira; Sumikawa, Joana Tomomi; Castro, Eloísa Dognani; Batista, Fabricio Pereira; Paredes-Gamero, Edgar; Oliveira, Lilian Carolina; Guerra, Izabel Monastério; Peres, Giovani Bravin; Cavalheiro, Renan Pelluzzi; Juliano, Luiz; Nazário, Afonso Pinto; Facina, Gil; Tsai, Siu Mui; Oliva, Maria Luiza Vilela; Girão, Manoel João Batista Castello

    2017-02-07

    Cancer progression is associated with an evolving tissue interface of direct epithelial-tumor microenvironment interactions. In biopsies of human breast tumors, extensive alterations in molecular pathways are correlated with cancer staging on both sides of the tumor-stroma interface. These interactions provide a pivotal paracrine signaling to induce malignant phenotype transition, the epithelial-mesenchymal transition (EMT). We explored how the direct contact between platelets-fibrin bundles primes metastasis using platelet-rich plasma (PRP) as a source of growth factors and mimics the provisional fibrin matrix between actively growing breast cancer cells and the tumor stroma. We have demonstrated PRP functions, modulating cell proliferation that is tumor-subtype and cancer cell-type-specific. Epithelial and stromal primary cells were prepared from breast cancer biopsies from 21 women with different cancer subtypes. Cells supplemented with PRP were immunoblotted with anti-phospho and total Src-Tyr-416, FAK-Try-925, E-cadherin, N-cadherin, TGF-β, Smad2, and Snail monoclonal antibodies. Breast tumor cells from luminal B and HER2 subtypes showed the most malignant profiles and the expression of thrombin and other classes of proteases at levels that were detectable through FRET peptide libraries. The angiogenesis process was investigated in the interface obtained between platelet-fibrin-breast tumor cells co-cultured with HUVEC cells. Luminal B and HER2 cells showed robust endothelial cell capillary-like tubes ex vivo. The studied interface contributes to the attachment of endothelial cells, provides a source of growth factors, and is a solid substrate. Thus, replacement of FBS supplementation with PRP supplementation represents an efficient and simple approach for mimicking the real multifactorial tumor microenvironment.

  17. Interface between breast cancer cells and the tumor microenvironment using platelet-rich plasma to promote tumor angiogenesis - influence of platelets and fibrin bundles on the behavior of breast tumor cells

    PubMed Central

    Andrade, Sheila Siqueira; Sumikawa, Joana Tomomi; Castro, Eloísa Dognani; Batista, Fabricio Pereira; Paredes-Gamero, Edgar; Oliveira, Lilian Carolina; Guerra, Izabel Monastério; Peres, Giovani Bravin; Cavalheiro, Renan Pelluzzi; Juliano, Luiz; Nazário, Afonso Pinto; Facina, Gil; Tsai, Siu Mui; Oliva, Maria Luiza Vilela; Girão, Manoel João Batista Castello

    2017-01-01

    Cancer progression is associated with an evolving tissue interface of direct epithelial-tumor microenvironment interactions. In biopsies of human breast tumors, extensive alterations in molecular pathways are correlated with cancer staging on both sides of the tumor-stroma interface. These interactions provide a pivotal paracrine signaling to induce malignant phenotype transition, the epithelial-mesenchymal transition (EMT). We explored how the direct contact between platelets-fibrin bundles primes metastasis using platelet-rich plasma (PRP) as a source of growth factors and mimics the provisional fibrin matrix between actively growing breast cancer cells and the tumor stroma. We have demonstrated PRP functions, modulating cell proliferation that is tumor-subtype and cancer cell-type-specific. Epithelial and stromal primary cells were prepared from breast cancer biopsies from 21 women with different cancer subtypes. Cells supplemented with PRP were immunoblotted with anti-phospho and total Src-Tyr-416, FAK-Try-925, E-cadherin, N-cadherin, TGF-β, Smad2, and Snail monoclonal antibodies. Breast tumor cells from luminal B and HER2 subtypes showed the most malignant profiles and the expression of thrombin and other classes of proteases at levels that were detectable through FRET peptide libraries. The angiogenesis process was investigated in the interface obtained between platelet-fibrin-breast tumor cells co-cultured with HUVEC cells. Luminal B and HER2 cells showed robust endothelial cell capillary-like tubes ex vivo. The studied interface contributes to the attachment of endothelial cells, provides a source of growth factors, and is a solid substrate. Thus, replacement of FBS supplementation with PRP supplementation represents an efficient and simple approach for mimicking the real multifactorial tumor microenvironment. PMID:28187434

  18. Expression of connective tissue growth factor (CTGF/CCN2) in breast cancer cells is associated with increased migration and angiogenesis

    PubMed Central

    CHIEN, WENWEN; O’KELLY, JAMES; LU, DANING; LEITER, AMANDA; SOHN, JULIA; YIN, DONG; KARLAN, BETH; VADGAMA, JAY; LYONS, KAREN M.; KOEFFLER, H. PHILLIP

    2013-01-01

    Connective tissue growth factor (CTGF/CCN2) belongs to the CCN family of matricellular proteins, comprising Cyr61, CTGF, NovH and WISP1-3. The CCN proteins contain an N-terminal signal peptide followed by four conserved domains sharing sequence similarities with the insulin-like growth factor binding proteins, von Willebrand factor type C repeat, thrombospondin type 1 repeat, and a C-terminal growth factor cysteine knot domain. To investigate the role of CCN2 in breast cancer, we transfected MCF-7 cells with full-length CCN2, and with four mutant constructs in which one of the domains had been deleted. MCF-7 cells stably expressing full-length CCN2 demonstrated reduced cell proliferation, increased migration in Boyden chamber assays and promoted angiogenesis in chorioallantoic membrane assays compared to control cells. Deletion of the C-terminal cysteine knot domain, but not of any other domain-deleted mutants, abolished activities mediated by full-length CCN2. We have dissected the role of CCN2 in breast tumorigenesis on a structural basis. PMID:21455569

  19. Breast Cancer Prevention

    MedlinePlus

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Prevention (PDQ®)–Patient Version What is prevention? Go ... from starting. Risk-reducing surgery . General Information About Breast Cancer Key Points Breast cancer is a disease in ...

  20. Breast cancer.

    PubMed

    Pearce, Lynne

    2016-08-17

    Essential facts Breast cancer is the most common cancer in the UK, with around 60,000 new cases diagnosed each year, according to the charity Breast Cancer Care. Over a lifetime, women have a one in eight risk of developing it.

  1. A pilot study on plasma levels of micro-RNAs involved in angiogenesis and vascular maturation in patients with breast cancer.

    PubMed

    Kontomanolis, Emmanuel; Mitrakas, Achilleas; Giatromanolaki, Alexandra; Kareli, Dimitra; Panteliadou, Marianthi; Pouliliou, Stamatia; Koukourakis, Michael I

    2017-02-01

    Micro-RNAs (miRNAs) have a complex role in carcinogenesis and tumour progression. Several miRNAs, such as miR-221, miR-27b and miR-132, have been implicated in the regulation of VEGF tumour angiogenic activity. In this pilot study, we assessed angiogenesis and DLL4+ vascular maturation index (VMI) in breast cancer tissues, in parallel with the plasma levels of the above-mentioned miRNAs. Significantly higher than control samples pre-operative levels were recorded in 10/11, 7/11 and 9/11 cases for the miR-221, miR-27b and miR-132, respectively. Seven days after surgery, a significant reduction of these miRNAs was noted in 6/11, 3/11 and 2/11 cases, respectively. High pre-operative levels of miR-27b were linked with node metastasis (p = 0.04). High pre-operative levels of miR-132 were linked with small tumours (p = 0.03) and her2 overexpression (p = 0.003). The DLL4+ VMI ranged from 26 to 69% (median 45%). Patients with poor DLL4+ VMI had significantly high pre-operative and post-operative levels of miR-221 (p = 0.01 and 0.02, respectively) and high post-operative levels of miR-132 (p = 0.02). It is concluded that angiogenesis-related miRs as detected in the plasma of patients may prove of a useful tool in the identification of patients with poor vascular maturation and high risk to develop metastasis. Whether such miRs may identify patients who would benefit from vascular normalization policies is a hypothesis that emerges from the current study.

  2. Anti-αvβ3 antibody guided three-step pretargeting approach using magnetoliposomes for molecular magnetic resonance imaging of breast cancer angiogenesis.

    PubMed

    Yan, Chenggong; Wu, Yuankui; Feng, Jie; Chen, Wufan; Liu, Xiang; Hao, Peng; Yang, Ruimeng; Zhang, Juan; Lin, Bingquan; Xu, Yikai; Liu, Ruiyuan

    2013-01-01

    Pretargeting of biomarkers with nanoparticles in molecular imaging is promising to improve diagnostic specificity and realize signal amplification, but data regarding its targeting potential in magnetic resonance (MR) imaging are limited. The purpose of this study was to evaluate the tumor angiogenesis targeting efficacy of the anti-αvβ3 antibody guided three-step pretargeting approach with magnetoliposomes. Polyethylene glycol-modified and superparamagnetic iron oxide-encapsulated magnetoliposomes with and without biotin were synthesized and characterized. The cytotoxicity of both probes was evaluated using the methyl thiazdyl tetrazolium assay, and their cellular uptake by mouse macrophage was visualized using Prussian blue staining. Three-step pretargeting MR imaging was performed on MDA-MB-435S breast cancer-bearing mice by intravenous administration of biotinylated anti-αvβ3 monoclonal antibodies (first step), followed by avidin and streptavidin (second step), and by biotinylated magnetoliposomes or magnetoliposomes in the targeted or nontargeted group, respectively (third step). The specificity of αvβ3 targeting was assessed by histologic examinations. The developed magnetoliposomes were superparamagnetic and biocompatible as confirmed by cell toxicity assay. The liposomal bilayer and polyethylene glycol modification protected Fe(3)O(4) cores from uptake by macrophage cells. MR imaging by three-step pretargeting resulted in a greater signal enhancement along the tumor periphery, occupying 7.0% of the tumor area, compared with 2.0% enhancement of the nontargeted group (P < 0.05). Histologic analysis demonstrated the targeted magnetoliposomes colocalized with neovasculature, which was responsible for the MR signal decrease. These results indicate that our strategy for MR imaging of αvβ3-integrin is an effective means for sensitive detection of tumor angiogenesis, and may provide a targetable nanodelivery system for anticancer drugs.

  3. Breast cancer screening

    MedlinePlus

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

  4. Endoscopic Breast Surgery in Treating Patients With Breast Cancer

    ClinicalTrials.gov

    2014-02-05

    Male Breast Cancer; 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

  5. Breast Cancer: Treatment Options

    MedlinePlus

    ... Breast Cancer > Breast Cancer: Treatment Options Request Permissions Breast Cancer: Treatment Options Approved by the Cancer.Net Editorial ... recommendations for ovarian ablation . Hormonal therapy for metastatic breast cancer Hormonal therapies are also commonly used to treat ...

  6. Breast Cancer

    MedlinePlus

    ... how early the cancer was diagnosed. Left untreated, breast cancer can spread to other parts of the body, including internal organs. This could cause serious health problems or be fatal. It is very important to get treatment as soon as possible.Living with cancer during ...

  7. Learning about Breast Cancer

    MedlinePlus

    ... genetic terms used on this page Learning About Breast Cancer What do we know about heredity and breast ... Cancer What do we know about heredity and breast cancer? Breast cancer is a common disease. Each year, ...

  8. Surgery for Breast Cancer

    MedlinePlus

    ... Oncology . 5th ed. Philadelphia, Pa: Elsevier; 2014. Last Medical Review: June 1, 2016 Last Revised: August 18, 2016 Breast Cancer Treatment Surgery for Breast Cancer Radiation for Breast Cancer Chemotherapy for Breast Cancer Hormone ...

  9. 6 Common Cancers - Breast Cancer

    MedlinePlus

    ... Home Current Issue Past Issues 6 Common Cancers - Breast Cancer Past Issues / Spring 2007 Table of Contents For ... slow her down. Photo: AP Photo/Brett Flashnick Breast Cancer Breast cancer is a malignant (cancerous) growth that ...

  10. Suppression of NFkB by Tetrathiomolybdate Inhibits Tumor Angiogenesis and Enhances Apoptosis in Human Breast Cancers

    DTIC Science & Technology

    2005-05-01

    Q. P., L. W. B., C. G. K., S. D. M.], University of Michigan Medical tumors, including breast, ovarian, colon, pancreatic, thyroid , School, Ann Arbor...while AP1 and SP1 binding ties, inhibited NFKB activity in DAOY medulloblastoma cells activities were unchanged. Taken together, these results (16

  11. Semaphorin signaling in angiogenesis, lymphangiogenesis and cancer

    PubMed Central

    Sakurai, Atsuko; Doci, Colleen; Gutkind, J Silvio

    2012-01-01

    Angiogenesis, the formation of new blood vessels from preexisting vasculature, is essential for many physiological processes, and aberrant angiogenesis contributes to some of the most prevalent human diseases, including cancer. Angiogenesis is controlled by delicate balance between pro- and anti-angiogenic signals. While pro-angiogenic signaling has been extensively investigated, how developmentally regulated, naturally occurring anti-angiogenic molecules prevent the excessive growth of vascular and lymphatic vessels is still poorly understood. In this review, we summarize the current knowledge on how semaphorins and their receptors, plexins and neuropilins, control normal and pathological angiogenesis, with an emphasis on semaphorin-regulated anti-angiogenic signaling circuitries in vascular and lymphatic endothelial cells. This emerging body of information may afford the opportunity to develop novel anti-angiogenic therapeutic strategies. PMID:22157652

  12. Protective Role of Selenium Compounds on the Proliferation, Apoptosis, and Angiogenesis of a Canine Breast Cancer Cell Line.

    PubMed

    Liu, Yuzhi; Li, Wenyu; Guo, Mengyao; Li, Chengye; Qiu, Changwei

    2016-01-01

    We herein examined the effects of different doses, forms, and compatibilities of selenium on a canine mammary gland tumor cell line, CTM1211, and explored the related mechanisms. Three selenium compounds, sodium selenite (SSE), methylseleninic acid (MSA), and methylselenocysteine (MSC), were selected for these experiments, and cyclophosphamide (CTX) served as a positive control. In the cell viability assay, the cell viability of each group at 48/72 h decreased significantly compared with the control group (p < 0.05), and the cell viability of the CTX + MSA group was lower than that of CTX and MSA groups (p < 0.05). Moreover, the inhibitory effect of selenium on cell proliferation was time-dependent but not concentration-dependent. In the cell apoptosis assay, the apoptosis values of each group increased significantly compared with the control group, and the apoptosis values of the CTX + MSA group increased the most significantly (p < 0.01). The protein and mRNA expression levels of vascular endothelial growth factor-alpha (VEGF-alpha), angiopoietin-2 (Ang-2), and hypoxia inducible factor-1 alpha (HIF-1 alpha) were downregulated in each group, while that of phosphatase and tensin homolog (PTEN) were upregulated (p < 0.05). In conclusion, these three selenium compounds, especially MSA, could significantly inhibit the viability and growth of the CTM1211 cell line, which is partly due to the induction of apoptosis and regulation of tumor angiogenesis.

  13. Risks of Breast Cancer Screening

    MedlinePlus

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Screening (PDQ®)–Patient Version What is screening? Go ... cancer screening: Cancer Screening Overview General Information About Breast Cancer Key Points Breast cancer is a disease in ...

  14. Recurrent Breast Cancer

    MedlinePlus

    ... you may have received after your first breast cancer diagnosis was intended to kill any cancer cells that ... 35 at the time of their original breast cancer diagnosis, face a higher risk of recurrent breast cancer. ...

  15. Inhibition of breast tumor growth and angiogenesis by a medicinal herb: Ocimum sanctum

    PubMed Central

    Nangia-Makker, Pratima; Tait, Larry; Hogan, Victor; Shekhar, Malathy P.V.; Funasaka, Tatsuyoshi; Raz, Avraham

    2013-01-01

    Ocimum sanctum (OS) is a traditionally used medicinal herb, which shows anti-oxidant, anti-carcinogenic, radio-protective and free radical scavenging properties. So far no detailed studies have been reported on its effects on human cancers. Thus, we analyzed its effects on human breast cancer utilizing in vitro and in vivo methodologies. Aqueous extracts were prepared from the mature leaves of Ocimum sanctum cultivated devoid of pesticides. Tumor progression and angiogenesis related processes like chemotaxis, proliferation, apoptosis, 3-dimensional growth and morphogenesis, angiogenesis, and tumor growth were studied in the presence or absence of the extract and in some experiments a comparison was made with purified commercially available eugenol, apigenin and ursolic acid. Aqueous OS leaf extract inhibits proliferation, migration, anchorage independent growth, three dimensional growth and morphogenesis, and induction of COX-2 protein in breast cancer cells. A comparative analysis with eugenol, apigenin and ursolic acid showed that the inhibitory effects on chemotaxis and three dimensional morphogenesis of breast cancer cells were specific to OS extract. In addition, OS extracts also reduced tumor size and neoangiogenesis in a MCF10 DCIS.com xenograft model of human DCIS. This is the first detailed report showing that OS leaf extract may be of value as a breast cancer preventive and therapeutic agent and might be considered as additional additive in the arsenal of components aiming at combating breast cancer progression and metastasis. PMID:17437270

  16. Understanding a Breast Cancer Diagnosis

    MedlinePlus

    ... Category Cancer A-Z Breast Cancer Understanding a Breast Cancer Diagnosis If you’ve been diagnosed with breast ... cancer or how fast it’s growing. Types of Breast Cancer There are several types of breast cancer. The ...

  17. Antiangiogenic therapy for breast cancer

    PubMed Central

    2010-01-01

    Angiogenesis is an important component of cancer growth, invasion and metastasis. Therefore, inhibition of angiogenesis is an attractive strategy for treatment of cancer. We describe existing clinical trials of antiangiogenic agents and the challenges facing the clinical development and optimal use of these agents for the treatment of breast cancer. Currently, the most promising approach has been the use of bevacizumab, a humanized monoclonal antibody directed against the most potent pro-angiogenic factor, vascular endothelial growth factor (VEGF). Small molecular inhibitors of VEGF tyrosine kinase activity, such as sorafenib, appear promising. While, the role of sunitinib and inhibitors of mammalian target of rapamycin (mTOR) in breast cancer has to be defined. Several unanswered questions remain, such as choice of drug(s), optimal duration of therapy and patient selection criteria. PMID:21067536

  18. Targeting Angiogenesis for Treatment of Human Cancer

    PubMed Central

    Somani, R. R.; Bhanushali, U. V.

    2013-01-01

    Recent advances in cancer research highlighted the importance of target-specific drug discovery. In view of these advances, the most important mechanism in tumour growth is its ability to stimulate the formation of blood capillaries around itself called tumour-driven angiogenesis. Hence targeting the angiogenesis, inhibits the growth of blood vessels around it and responsible for death of the tumour due to starvation and accumulation of toxic waste. The therapy, thus, indirectly cytotoxic to the tumour cells by targeting newly developing blood vessels. In this review, we summarised the various antiangiogenic agents with their clinical uses and current status. PMID:23901154

  19. Breast Cancer -- Male

    MedlinePlus

    ... 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 ...

  20. Breast Cancer Overview

    MedlinePlus

    ... are here Home > Types of Cancer > Breast Cancer Breast Cancer This is Cancer.Net’s Guide to Breast Cancer. Use the menu below to choose the Overview/ ... social workers, and patient advocates. Cancer.Net Guide Breast Cancer Introduction Statistics Medical Illustrations Risk Factors and Prevention ...

  1. Impact of ER520, a candidate of selective estrogen receptor modulators, on in vitro cell growth, migration, invasion, angiogenesis and in vivo tumor xenograft of human breast cancer cells.

    PubMed

    Wang, Lijun; Wang, Ying; Du, Huaqing; Jiang, Yao; Tang, Zhichao; Liu, Hongyi; Xiang, Hua; Xiao, Hong

    2015-12-01

    ER520, a derivative of indenoisoquinoline, is a patented compound. This study was designed to screen its biological properties and to evaluate its antineoplastic and antiangiogenic effect. Western blot was employed to monitor the ERα and ERβ protein expression in human breast cancer MCF-7 cells and endometrial carcinoma Ishikawa cells. MTT assay was employed to determine cell proliferation. Cell adhesion, scratch and Transwell assay were utilized to estimate the ability of cellular adhesion, migration and invasion. ELISA kit was applied to detect the VEGF products in culture medium. In addition, the inhibitory effect of ER520 on the vessel-like construction of HUVEC cells and the angiogenesis of chicken embryos was investigated. The efficiency of ER520 on tumor growth in nude mice was also assessed. ER520 inhibited the expression of ERα in MCF-7 and Ishikawa cells, while it increased ERβ protein level. ER520 also suppressed the proliferation of MCF-7 and Ishikawa cells. Due to its remarkably negative role in cell adhesion, migration and invasion, ER520 showed a potential ability of inhibiting tumor metastasis. Meanwhile, ER520 reduced the VEGF secretion of MCF-7 and Ishikawa cells, prevented the formation of VEGF-stimulated tubular structure and the cell migration of HUVEC cells, and inhibited the angiogenesis of chicken chorioallantoic membrane. Animal experiment also demonstrated that ER520 could frustrate the in vivo tumor growth and the inhibitory ratio was 48.5 % compared with control group. Our findings indicate that ER520 possesses the competence to be a candidate against breast cancer and angiogenesis.

  2. Breast Cancer (For Kids)

    MedlinePlus

    ... de los dientes Video: Getting an X-ray Breast Cancer KidsHealth > For Kids > Breast Cancer Print A A ... for it when they are older. What Is Breast Cancer? The human body is made of tiny building ...

  3. Male Breast Cancer

    MedlinePlus

    Although breast cancer is much more common in women, men can get it too. It happens most often to men ... usually aren't cancer. However, most men with breast cancer have lumps. Other breast symptoms can include Dimpled ...

  4. Breast Cancer Trends

    MedlinePlus

    ... Breast Cancer Funding: Young Breast Cancer Survivors Funding: Breast Cancer Genomics Statistics Rates by Race and Ethnicity Rates by State Risk by Age Trends What CDC Is Doing Research African American Women and Mass Media Campaign Public Service Announcements Print ...

  5. Breast Cancer Surgery

    MedlinePlus

    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 ...

  6. Angiogenesis Inhibitors in Breast Cancer

    DTIC Science & Technology

    2005-04-01

    Westling et al., 2002). 3) Cleavage of TSP-I is not shared by ADAMTS-4. ADAMTS-1 and ADAMTS-4 display high sequence homology and more importantly, both...Manzaneque JC, Westling J, Thai SN, Luque A, Knauper V, Murphy G, Sandy JD, Iruela-Arispe ML. ADAMTS1 cleaves aggrecan at multiple sites and is...differentially inhibited by metalloproteinase inhibitors. Biochem Biophys Res Commun. 2002 Apr 26;293(1):501-8. * Sandy JD, Westling J, Kenagy RD, Iruela-Arispe

  7. Molecular Disruption of Breast Tumor Angiogenesis

    DTIC Science & Technology

    2004-07-01

    Release; Distribution Unlimited 13. ABSTRACT (Maximum 200 Words) Endothelial cells must express plasminogen activator inhibitor type-I (PAI-I) in order to...angiogenic target. 14. SUBJECT TERMS 15. NUMBER OF PAGES Angiogenesis, gene therapy, plasminogen activator inhibitor -l 64 16. PRICE CODE 17. SECURITY...highly-dependent on the temporally-regulated and focalized activity of several extracellular proteases and protease inhibitors involving members of both

  8. Breast Cancer Disparities

    MedlinePlus

    ... 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 ...

  9. Breast cancer in men

    MedlinePlus

    ... 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 ...

  10. Angiogenesis in prostate cancer: onset, progression and imaging.

    PubMed

    Russo, Giovanna; Mischi, Massimo; Scheepens, Wout; De la Rosette, Jean J; Wijkstra, Hessel

    2012-12-01

    What's known on the subject? and What does the study add? Today, angiogenesis is known to play a key role in cancer growth and development. Emerging cancer treatments are based on the suppression of angiogenesis, and modern imaging techniques investigate changes in the microvasculature that are caused by angiogenesis. As for other forms of cancers, angiogenesis is well recognised as a fundamental process in the development of prostate cancer. The novelty of this extensive report on angiogenesis in cancer, with particular attention on prostate cancer and the imaging techniques able to detect it, is the new prospective to the subject. In contrast with the other available reviews, this report goes from 'theory' to 'practice', establishing a clear link between angiogenesis development and imaged angiogenesis features. Once the key role of angiogenesis in the development of cancer and in particular prostate cancer has been fully described, attention is turned to the current imaging methods with the potential to assess the angiogenesis process and, as a consequence, to detect and localise prostate cancer. • As confirmed by all available statistics, cancer represents a major clinical and societal problem in the developed world. The form of cancer with the highest incidence in men is prostate cancer. For prostate cancer, as well as for most forms of cancer, detection of the disease at an early stage is critical to reduce mortality and morbidity. • Today, it is well known that pathological angiogenesis represents a crucial step in cancer development and progression. Comparable with most forms of cancer, angiogenesis also plays a fundamental role for prostate cancer growth. • As a consequence, angiogenesis is an ideal target not only for novel anti-angiogenic therapies, but also for modern imaging techniques that aim at cancer localisation by detection of angiogenic microvascular changes. • These techniques are mainly based on magnetic resonance, ultrasound, and

  11. Hypercholesterolemia induces angiogenesis and accelerates growth of breast tumors in vivo.

    PubMed

    Pelton, Kristine; Coticchia, Christine M; Curatolo, Adam S; Schaffner, Carl P; Zurakowski, David; Solomon, Keith R; Moses, Marsha A

    2014-07-01

    Obesity and metabolic syndrome are linked to an increased prevalence of breast cancer among postmenopausal women. A common feature of obesity, metabolic syndrome, and a Western diet rich in saturated fat is a high level of circulating cholesterol. Epidemiological reports investigating the relationship between high circulating cholesterol levels, cholesterol-lowering drugs, and breast cancer are conflicting. Here, we modeled this complex condition in a well-controlled, preclinical animal model using innovative isocaloric diets. Female severe combined immunodeficient mice were fed a low-fat/no-cholesterol diet and then randomized to four isocaloric diet groups: low-fat/no-cholesterol diet, with or without ezetimibe (cholesterol-lowering drug), and high-fat/high-cholesterol diet, with or without ezetimibe. Mice were implanted orthotopically with MDA-MB-231 cells. Breast tumors from animals fed the high-fat/high-cholesterol diet exhibited the fastest progression. Significant differences in serum cholesterol level between groups were achieved and maintained throughout the study; however, no differences were observed in intratumoral cholesterol levels. To determine the mechanism of cholesterol-induced tumor progression, we analyzed tumor proliferation, apoptosis, and angiogenesis and found a significantly greater percentage of proliferating cells from mice fed the high-fat/high-cholesterol diet. Tumors from hypercholesterolemic animals displayed significantly less apoptosis compared with the other groups. Tumors from high-fat/high-cholesterol mice had significantly higher microvessel density compared with tumors from the other groups. These results demonstrate that hypercholesterolemia induces angiogenesis and accelerates breast tumor growth in vivo.

  12. Targeting angiogenesis with integrative cancer therapies.

    PubMed

    Yance, Donald R; Sagar, Stephen M

    2006-03-01

    An integrative approach for managing a patient with cancer should target the multiple biochemical and physiological pathways that support tumor development while minimizing normal tissue toxicity. Angiogenesis is a key process in the promotion of cancer. Many natural health products that inhibit angiogenesis also manifest other anticancer activities. The authors will focus on natural health products (NHPs) that have a high degree of antiangiogenic activity but also describe some of their many other interactions that can inhibit tumor progression and reduce the risk of metastasis. NHPs target various molecular pathways besides angiogenesis, including epidermal growth factor receptor (EGFR), the HER-2/neu gene, the cyclooxygenase-2 enzyme, the NF-kB transcription factor, the protein kinases, Bcl-2 protein, and coagulation pathways. The herbalist has access to hundreds of years of observational data on the anticancer activity of many herbs. Laboratory studies are confirming the knowledge that is already documented in traditional texts. The following herbs are traditionally used for anticancer treatment and are antiangiogenic through multiple interdependent processes that include effects on gene expression, signal processing, and enzyme activities: Artemisia annua (Chinese wormwood), Viscum album (European mistletoe), Curcuma longa (turmeric), Scutellaria baicalensis (Chinese skullcap), resveratrol and proanthocyanidin (grape seed extract), Magnolia officinalis (Chinese magnolia tree), Camellia sinensis (green tea), Ginkgo biloba, quercetin, Poria cocos, Zingiber officinale (ginger), Panax ginseng, Rabdosia rubescens (rabdosia), and Chinese destagnation herbs. Quality assurance of appropriate extracts is essential prior to embarking on clinical trials. More data are required on dose response, appropriate combinations, and potential toxicities. Given the multiple effects of these agents, their future use for cancer therapy probably lies in synergistic combinations

  13. Genetics Home Reference: breast cancer

    MedlinePlus

    ... cancers . A small percentage of all breast cancers cluster in families. These cancers are described as hereditary ... will develop breast cancer . Some breast cancers that cluster in families are associated with inherited mutations in ...

  14. Male Breast Cancer

    MedlinePlus

    ... or to other parts of the body. Where breast cancer begins in men Everyone is born with a ... skin around the nipple. Inherited genes that increase breast cancer risk Some men inherit abnormal (mutated) genes from ...

  15. Breast cancer staging

    MedlinePlus

    ... 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. ...

  16. Breast Cancer Early Detection and Diagnosis

    MedlinePlus

    ... 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 ...

  17. VEGF-mediated angiogenesis links EMT-induced cancer stemness to tumor initiation.

    PubMed

    Fantozzi, Anna; Gruber, Dorothea C; Pisarsky, Laura; Heck, Chantal; Kunita, Akiko; Yilmaz, Mahmut; Meyer-Schaller, Nathalie; Cornille, Karen; Hopfer, Ulrike; Bentires-Alj, Mohamed; Christofori, Gerhard

    2014-03-01

    An epithelial-mesenchymal transition (EMT) underlies malignant tumor progression and metastatic spread by enabling cancer cells to depart from the primary tumor, invade surrounding tissue, and disseminate to distant organs. EMT also enriches for cancer stem cells (CSC) and increases the capacity of cancer cells to initiate and propagate tumors upon transplantation into immune-deficient mice, a major hallmark of CSCs. However, the molecular mechanisms promoting the tumorigenicity of cancer cells undergoing an EMT and of CSCs have remained widely elusive. We here report that EMT confers efficient tumorigenicity to murine breast cancer cells by the upregulated expression of the proangiogenic factor VEGF-A and by increased tumor angiogenesis. On the basis of these data, we propose a novel interpretation of the features of CSCs with EMT-induced, VEGF-A-mediated angiogenesis as the connecting mechanism between cancer cell stemness and tumor initiation.

  18. Breast Cancer (For Kids)

    MedlinePlus

    ... 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 ...

  19. Schizophrenia and cancer: is angiogenesis a missed link?

    PubMed

    Lopes, Rui; Soares, Raquel; Figueiredo-Braga, Margarida; Coelho, Rui

    2014-03-03

    Cancer prevalence and risk in schizophrenia (SZ) patients, as well as their implicated molecular pathways, is a debate that has become increasingly appreciated, despite lacking evidence. Since angiogenesis is imbalanced in both conditions, a non-systematic review of the existing literature using the PubMed database was performed to summarize current knowledge and to elucidate hypothesis regarding the reduced incidence of cancer in SZ, exploring possible angiogenesis biology aspects that can be interrelated both with SZ and cancer. Some lines of evidence based in epidemiology, genetic, molecular and biochemical studies suggest a putative interplay between SZ pathophysiology and angiogenesis, involving different molecular pathways and also influencing cancer biology. Studying angiogenesis in SZ and its implications to cancer is an unexplored field that could provide more insightful knowledge regarding its pathophysiology and promote the development of treatment applications.

  20. Anti-angiogenesis therapy and gap junction inhibition reduce MDA-MB-231 breast cancer cell invasion and metastasis in vitro and in vivo

    PubMed Central

    Zibara, Kazem; Awada, Zahraa; Dib, Leila; El-Saghir, Jamal; Al-Ghadban, Sara; Ibrik, Aida; El-Zein, Nabil; El-Sabban, Marwan

    2015-01-01

    Cancer cells secrete VEGF, which plays a key role in their growth, invasion, extravasation and metastasis. Direct cancer cell-endothelial cell interaction, mediated by gap junctions, is of critical importance in the extravasation process. In this study, we evaluated avastin (Av), an anti-VEGF antibody; and oleamide (OL), a gap junction inhibitor, using MDA-MB-231 human breast cancer cells in vitro and a xenograft murine model in vivo. Results showed that Av/OL significantly decreased proliferation, induced cell cycle arrest and decreased migration and invasion of MDA-MB-231 cells in vitro. In addition, Av/OL significantly decreased homo and hetero-cellular communication interaction between MDA-MDA and MDA-endothelial cells, respectively. The expression levels of several factors including VEGF, HIF1α, CXCR4, Cx26, Cx43, and MMP9 were attenuated upon Av/OL treatment in vitro. On the other hand, avastin, but not oleamide, reduced tumor size of NSG mice injected subdermally (s.d.) with MDA-MB-231 cells, which was also associated with increased survival. Furthermore, Av but also OL, separately, significantly increased the survival rate, and reduced pulmonary and hepatic metastatic foci, of intravenously (i.v.) injected mice. Finally, OL reduced MMP9 protein expression levels, better than Av and in comparisons to control, in the lungs of MDA-MB-231 i.v. injected NSG mice. In conclusion, while avastin has anti-angiogenic, anti-tumor and anti-metastatic activities, oleamide has anti-metastatic activity, presumably at the extravasation level, providing further evidence for the role of gap junction intercellular communication (GJIC) in cancer cell extravasation. PMID:26218768

  1. Breast Cancer Rates by State

    MedlinePlus

    ... 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 ...

  2. Emerging Roles of ADAMTSs in Angiogenesis and Cancer

    PubMed Central

    Kumar, Saran; Rao, Nithya; Ge, Ruowen

    2012-01-01

    A Disintegrin-like And Metalloproteinase with ThromboSpondin motifs—ADAMTSs—are a multi-domain, secreted, extracellular zinc metalloproteinase family with 19 members in humans. These extracellular metalloproteinases are known to cleave a wide range of substrates in the extracellular matrix. They have been implicated in various physiological processes, such as extracellular matrix turnover, melanoblast development, interdigital web regression, blood coagulation, ovulation, etc. ADAMTSs are also critical in pathological processes such as arthritis, atherosclerosis, cancer, angiogenesis, wound healing, etc. In the past few years, there has been an explosion of reports concerning the role of ADAMTS family members in angiogenesis and cancer. To date, 10 out of the 19 members have been demonstrated to be involved in regulating angiogenesis and/or cancer. The mechanism involved in their regulation of angiogenesis or cancer differs among different members. Both angiogenesis-dependent and -independent regulation of cancer have been reported. This review summarizes our current understanding on the roles of ADAMTS in angiogenesis and cancer and highlights their implications in cancer therapeutic development. PMID:24213506

  3. Sorafenib for the treatment of breast cancer.

    PubMed

    Bronte, Giuseppe; Andreis, Daniele; Bravaccini, Sara; Maltoni, Roberta; Cecconetto, Lorenzo; Schirone, Alessio; Farolfi, Alberto; Fedeli, Anna; Serra, Patrizia; Donati, Caterina; Amadori, Dino; Rocca, Andrea

    2017-04-01

    Breast cancer treatment includes many options depending on the tumor clinicopathological profile, which groups breast cancer into various subtypes. Bevacizumab is currently the only drug capable of targeting angiogenesis in breast cancer. Sorafenib has also been studied in combination with other agents. Areas covered: Pharmacological aspects of sorafenib, including results from preclinical studies on breast cancer cells; findings about clinical efficacy and safety in both single-arm and randomized clinical trials; ongoing trials. Expert opinion: Since sorafenib as a single agent has shown limited efficacy in breast cancer, its combination with other drugs is under investigation. Dose reduction is the main challenge when sorafenib is combined with chemotherapy or endocrine therapy. Although randomized phase-II trials on sorafenib plus chemotherapy versus chemotherapy alone have shown potential benefits in progression-free survival, preliminary results from a phase-III study in combination with capecitabine are negative. The definitive results of this trial and results from other ongoing phase-II trials will determine further developments of sorafenib in breast cancer. Although these additional data could help determine the most appropriate dose, drug combination and patient settings, a confirmation of the preliminary negative results reported in the phase-III trial are likely to discourage further use of sorafenib in breast cancer, given its non-negligible toxicity, lack of predicting markers, and the number of more promising drugs for breast cancer.

  4. Pembrolizumab in Treating Patients With Triple-Negative Breast Cancer

    ClinicalTrials.gov

    2017-10-12

    Estrogen Receptor Negative; HER2/Neu Negative; Invasive Breast Carcinoma; Progesterone Receptor Negative; Stage 0 Breast Cancer; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-Negative Breast Carcinoma

  5. Male Breast Cancer

    PubMed Central

    Yalaza, Metin; İnan, Aydın; Bozer, Mikdat

    2016-01-01

    Male breast cancer (MBC) is a rare disease, accounting for less than 1% of all breast cancer diagnoses worldwide. Although breast carcinomas share certain characteristics in both genders, there are notable differences. Most studies on men with breast cancer are very small. Thus, most data on male breast cancer are derived from studies on females. However, when a number of these small studies are grouped together, we can learn more from them. This review emphasizes the incidence, etiology, clinical features, diagnosis, treatment, pathology, survival, and prognostic factors related to MBC.

  6. Predictive value of angiogenesis-related gene profiling in patients with HER2-negative metastatic breast cancer treated with bevacizumab and weekly paclitaxel

    PubMed Central

    Mendiola, Marta; Martínez-Marin, Virginia; Herranz, Jesús; Heredia, Victoria; Yébenes, Laura; Zamora, Pilar; Castelo, Beatriz; Pinto, Álvaro; Miguel, María; Díaz, Esther; Gámez, Angelo; Fresno, Juan Ángel; de Molina, Ana Ramírez; Hardisson, David; Espinosa, Enrique; Redondo, Andrés

    2016-01-01

    Bevacizumab plus weekly paclitaxel improves progression-free survival (PFS) in HER2-negative metastatic breast cancer (mBC), but its use has been questioned due to the absence of a predictive biomarker, lack of benefit in overall survival (OS) and increased toxicity. We examined the baseline tumor angiogenic-related gene expression of 60 patients with mBC with the aim of finding a signature that predicts benefit from this drug. Multivariate analysis by Lasso-penalized Cox regression generated two predictive models: one, named G-model, including 11 genes, and the other one, named GC-model, including 13 genes plus 5 clinical covariates. Both models identified patients with improved PFS (HR (Hazard Ratio) 2.57 and 4.04, respectively) and OS (HR 3.29 and 3.43, respectively). The G-model distinguished low and high risk patients in the first 6 months, whereas the GC-model maintained significance over time. PMID:26992213

  7. Developing phytoestrogens for breast cancer prevention.

    PubMed

    Liu, Mandy M; Huang, Ying; Wang, Jeffrey

    2012-12-01

    Breast cancer is one of the most common types of cancer in women, and is the second leading cause of cancer-related deaths in the United States. Chemoprevention using phytoestrogens (PEs) for breast cancer may be a valid strategy. PEs are phytochemicals with estrogen-like structures and can be classified into four types: isoflavones, lignans, stilbenes and coumestans. They are widely distributed in diet and herbs and have shown anti-cancer activity via mechanisms including estrogen receptor modulation, aromatase inhibition, and anti-angiogenesis. Genistein, daidzein and resveratrol are some of the most studied PE examples. Quality control in product manufacturing and clinical study design is a critical issue in developing them as clinically effective chemopreventive agents for breast cancer.

  8. Targeting SH2 domains in breast cancer.

    PubMed

    Morlacchi, Pietro; Robertson, Fredika M; Klostergaard, Jim; McMurray, John S

    2014-01-01

    Breast cancer is among the most commonly diagnosed cancer types in women worldwide and is the second leading cause of cancer-related disease in the USA. SH2 domains recruit signaling proteins to phosphotyrosine residues on aberrantly activated growth factor and cytokine receptors and contribute to cancer cell cycling, metastasis, angiogenesis and so on. Herein we review phosphopeptide mimetic and small-molecule approaches targeting the SH2 domains of Grb2, Grb7 and STAT3 that inhibit their targets and reduce proliferation in in vitro breast cancer models. Only STAT3 inhibitors have been evaluated in in vivo models and have led to tumor reduction. Taken together, these studies suggest that targeting SH2 domains is an important approach to the treatment of breast cancer.

  9. Cancer growth and spread are saltatory and phase-locked to the reproductive cycle through mediators of angiogenesis.

    PubMed

    Wood, Patricia A; Bove, Kathleen; You, Shaojin; Chambers, Ann; Hrushesky, William J M

    2005-07-01

    The frequency of breast cancer metastatic spread is affected by the menstrual cycle phase of its resection. Breast cancer growth, post-resection spread, and cure frequency are each modulated by the estrous cycle in C(3)HeB/FeJ mice. Tumor metastases are 2- to 3-fold more frequent when the resection is done during diestrus as compared with estrus. Tumor angiogenesis is essential for both cancer growth and lethal metastatic cancer spread. The balance between vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) modulates new blood vessel formation and blood vessel permeability. Sex hormones modulate the expression of these key angiogenesis regulators in the endometrium and uterus. We, therefore, asked whether the estrous cycle modulates the density of CD31-positive vessels within the tumor, the permeability of tumor blood vessels, levels of VEGF and bFGF immunoreactive protein in normal breast and breast cancer, and whether expression of these genes are modulated by the estrous cycle stage in C(3)HeB/FeJ mice. We find that tumor blood vessel density and blood volume do not vary throughout the cycle; however, tumor capillary permeability is regulated by the estrous cycle being highest in diestrus, the cycle stage associated with the highest cancer growth rate and the highest frequency of post-resection cancer metastasis. VEGF protein levels in breast cancer are >100-fold higher than in normal breast. VEGF protein in this mammary tumor varies with the estrus cycle with highest levels in proestrus. In a non-breast tumor, methylcholantrenene A sarcoma, from CD(2)F(1) mice, tumor VEGF protein also varies with the estrus cycle with highest levels in proestrus and diestrus. VEGF gene expression in the mammary tumor does not change significantly across the cycle, but is modulated by the cycle in normal breast tissue. bFGF protein concentration is 6-fold higher in normal breast than in breast cancer. bFGF protein pattern in both tumor and breast

  10. Hypercholesterolemia Induces Angiogenesis and Accelerates Growth of Breast Tumors in Vivo

    PubMed Central

    Pelton, Kristine; Coticchia, Christine M.; Curatolo, Adam S.; Schaffner, Carl P.; Zurakowski, David; Solomon, Keith R.; Moses, Marsha A.

    2015-01-01

    Obesity and metabolic syndrome are linked to an increased prevalence of breast cancer among postmenopausal women. A common feature of obesity, metabolic syndrome, and a Western diet rich in saturated fat is a high level of circulating cholesterol. Epidemiological reports investigating the relationship between high circulating cholesterol levels, cholesterol-lowering drugs, and breast cancer are conflicting. Here, we modeled this complex condition in a well-controlled, preclinical animal model using innovative isocaloric diets. Female severe combined immunodeficient mice were fed a low-fat/no-cholesterol diet and then randomized to four isocaloric diet groups: low-fat/no-cholesterol diet, with or without ezetimibe (cholesterol-lowering drug), and high-fat/high-cholesterol diet, with or without ezetimibe. Mice were implanted orthotopically with MDA-MB-231 cells. Breast tumors from animals fed the high-fat/high-cholesterol diet exhibited the fastest progression. Significant differences in serum cholesterol level between groups were achieved and maintained throughout the study; however, no differences were observed in intratumoral cholesterol levels. To determine the mechanism of cholesterol-induced tumor progression, we analyzed tumor proliferation, apoptosis, and angiogenesis and found a significantly greater percentage of proliferating cells from mice fed the high-fat/high-cholesterol diet. Tumors from hypercholesterolemic animals displayed significantly less apoptosis compared with the other groups. Tumors from high-fat/high-cholesterol mice had significantly higher microvessel density compared with tumors from the other groups. These results demonstrate that hypercholesterolemia induces angiogenesis and accelerates breast tumor growth in vivo. PMID:24952430

  11. Inflammatory Breast Cancer

    MedlinePlus

    ... red, or inflamed. Inflammatory breast cancer is rare, accounting for 1 to 5 percent of all breast ... Publications Site Map Digital Standards for NCI Websites POLICIES Accessibility Comment Policy Disclaimer FOIA Privacy & Security Reuse & ...

  12. Living as a Breast Cancer Survivor

    MedlinePlus

    ... a Breast Cancer Survivor Follow up Care After Breast Cancer Treatment Many women are relieved or excited to ... Menopausal Hormone Therapy After Breast Cancer More In Breast Cancer About Breast Cancer Risk and Prevention Early Detection ...

  13. Treating Male Breast Cancer by Stage

    MedlinePlus

    ... Men Treating Breast Cancer in Men Treatment of Breast Cancer in Men, by Stage Because there have been ... Doctor About Breast Cancer in Men? More In Breast Cancer In Men About Breast Cancer in Men Causes, ...

  14. Breast Cancer Risk in American Women

    MedlinePlus

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Risk in American Women On This Page What ... risk of developing the disease. Personal history of breast cancer : Women who have had breast cancer are more ...

  15. Do We Know What Causes Breast Cancer?

    MedlinePlus

    ... Research? Breast Cancer About Breast Cancer How Does Breast Cancer Form? Changes or mutations in DNA can cause ... please see our Content Usage Policy . More In Breast Cancer About Breast Cancer Risk and Prevention Early Detection ...

  16. Surgery for Breast Cancer in Men

    MedlinePlus

    ... Men Treating Breast Cancer in Men Surgery for Breast Cancer in Men The thought of surgery can be ... Doctor About Breast Cancer in Men? More In Breast Cancer In Men About Breast Cancer in Men Causes, ...

  17. Role of microRNA-34 family in cancer with particular reference to cancer angiogenesis.

    PubMed

    Maroof, Hamidreza; Salajegheh, Ali; Smith, Robert Anthony; Lam, Alfred King-Yin

    2014-10-01

    MicroRNA-34 is involved in pathogenesis in cancer by targeting different tumor-related genes. It could be a biomarker for predicting the prognosis of patients with cancer. In addition, miR-34 is involved in the tumor angiogenesis. Understanding the mechanism of the miR-34 in cancer and tumor angiogenesis will open horizons for development of anti-cancer and anti-angiogenesis drugs.

  18. Breast Cancer and Bone Loss

    MedlinePlus

    ... 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 ...

  19. Dietary Natural Products for Prevention and Treatment of Breast Cancer

    PubMed Central

    Li, Ya; Li, Sha; Meng, Xiao; Zhang, Jiao-Jiao

    2017-01-01

    Breast cancer is the most common cancer among females worldwide. Several epidemiological studies suggested the inverse correlation between the intake of vegetables and fruits and the incidence of breast cancer. Substantial experimental studies indicated that many dietary natural products could affect the development and progression of breast cancer, such as soy, pomegranate, mangosteen, citrus fruits, apple, grape, mango, cruciferous vegetables, ginger, garlic, black cumin, edible macro-fungi, and cereals. Their anti-breast cancer effects involve various mechanisms of action, such as downregulating ER-α expression and activity, inhibiting proliferation, migration, metastasis and angiogenesis of breast tumor cells, inducing apoptosis and cell cycle arrest, and sensitizing breast tumor cells to radiotherapy and chemotherapy. This review summarizes the potential role of dietary natural products and their major bioactive components in prevention and treatment of breast cancer, and special attention was paid to the mechanisms of action. PMID:28698459

  20. Dietary Natural Products for Prevention and Treatment of Breast Cancer.

    PubMed

    Li, Ya; Li, Sha; Meng, Xiao; Gan, Ren-You; Zhang, Jiao-Jiao; Li, Hua-Bin

    2017-07-08

    Breast cancer is the most common cancer among females worldwide. Several epidemiological studies suggested the inverse correlation between the intake of vegetables and fruits and the incidence of breast cancer. Substantial experimental studies indicated that many dietary natural products could affect the development and progression of breast cancer, such as soy, pomegranate, mangosteen, citrus fruits, apple, grape, mango, cruciferous vegetables, ginger, garlic, black cumin, edible macro-fungi, and cereals. Their anti-breast cancer effects involve various mechanisms of action, such as downregulating ER-α expression and activity, inhibiting proliferation, migration, metastasis and angiogenesis of breast tumor cells, inducing apoptosis and cell cycle arrest, and sensitizing breast tumor cells to radiotherapy and chemotherapy. This review summarizes the potential role of dietary natural products and their major bioactive components in prevention and treatment of breast cancer, and special attention was paid to the mechanisms of action.

  1. Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes.

    PubMed

    Dai, Xiaofeng; Xiang, Liangjian; Li, Ting; Bai, Zhonghu

    2016-01-01

    Breast cancer is a complex disease encompassing multiple tumor entities, each characterized by distinct morphology, behavior and clinical implications. Besides estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, novel biomarkers have shown their prognostic and predictive values, complicating our understanding towards to the heterogeneity of such cancers. Ten cancer hallmarks have been proposed by Weinberg to characterize cancer and its carcinogenesis. By reviewing biomarkers and breast cancer molecular subtypes, we propose that the divergent outcome observed from patients stratified by hormone status are driven by different cancer hallmarks. 'Sustaining proliferative signaling' further differentiates cancers with positive hormone receptors. 'Activating invasion and metastasis' and 'evading immune destruction' drive the differentiation of triple negative breast cancers. 'Resisting cell death', 'genome instability and mutation' and 'deregulating cellular energetics' refine breast cancer classification with their predictive values. 'Evading growth suppressors', 'enabling replicative immortality', 'inducing angiogenesis' and 'tumor-promoting inflammation' have not been involved in breast cancer classification which need more focus in the future biomarker-related research. This review novels in its global view on breast cancer heterogeneity, which clarifies many confusions in this field and contributes to precision medicine.

  2. Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes

    PubMed Central

    Dai, Xiaofeng; Xiang, Liangjian; Li, Ting; Bai, Zhonghu

    2016-01-01

    Breast cancer is a complex disease encompassing multiple tumor entities, each characterized by distinct morphology, behavior and clinical implications. Besides estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, novel biomarkers have shown their prognostic and predictive values, complicating our understanding towards to the heterogeneity of such cancers. Ten cancer hallmarks have been proposed by Weinberg to characterize cancer and its carcinogenesis. By reviewing biomarkers and breast cancer molecular subtypes, we propose that the divergent outcome observed from patients stratified by hormone status are driven by different cancer hallmarks. 'Sustaining proliferative signaling' further differentiates cancers with positive hormone receptors. 'Activating invasion and metastasis' and 'evading immune destruction' drive the differentiation of triple negative breast cancers. 'Resisting cell death', 'genome instability and mutation' and 'deregulating cellular energetics' refine breast cancer classification with their predictive values. 'Evading growth suppressors', 'enabling replicative immortality', 'inducing angiogenesis' and 'tumor-promoting inflammation' have not been involved in breast cancer classification which need more focus in the future biomarker-related research. This review novels in its global view on breast cancer heterogeneity, which clarifies many confusions in this field and contributes to precision medicine. PMID:27390604

  3. β-Blockers Reduce Breast Cancer Recurrence and Breast Cancer Death: A Meta-Analysis.

    PubMed

    Childers, W Kurtis; Hollenbeak, Christopher S; Cheriyath, Pramil

    2015-12-01

    The normal physiologic stress mechanism, mediated by the sympathetic nervous system, causes a release of the neurotransmitters epinephrine and norepinephrine. Preclinical data have demonstrated an effect on tumor progression and metastasis via the sympathetic nervous system mediated primarily through the β-adrenergic receptor (β-AR) pathway. In vitro data have shown an increase in tumor growth, migration, tumor angiogenesis, and metastatic spread in breast cancer through activation of the β-AR. Retrospective cohort studies on the clinical outcomes of β-blockers in breast cancer outcomes showed no clear consensus. The purpose of this study was to perform a systematic review and meta-analysis of the effect of β-blockers on breast cancer outcomes. A systematic review was performed using the Cochrane library and PubMed. Publications between the dates of January 2010 and December 2013 were identified. Available hazard ratios (HRs) were extracted for breast cancer recurrence, breast cancer death, and all-cause mortality and pooled using a random effects meta-analysis. A total of 7 studies contained results for at least 1 of the outcomes of breast cancer recurrence, breast cancer death, or all-cause mortality in breast cancer patients receiving β-blockers. In the 5 studies that contained results for breast cancer recurrence, there was no statistically significant risk reduction (HR, 0.67; 95% confidence interval [CI], 0.39-1.13). Breast cancer death results were contained in 4 studies, which also suggested a significant reduction in risk (HR, 0.50; 95% CI, 0.32-0.80). Among the 4 studies that reported all-cause mortality, there was no significant effect of β-blockers on risk (HR, 1.02; 95% CI, 0.75-1.37). Results of this systematic review and meta-analysis suggest that the use of β-blockers significantly reduced risk of breast cancer death among women with breast cancer.

  4. Angiogenesis factors involved in the pathogenesis of colorectal cancer.

    PubMed

    Mihalache, A; Rogoveanu, I

    2014-01-01

    Colorectal cancer stands at the top of oncologic pathology in the world, and in the same measure in Romania because is the third most frequent cancer diagnosed in men and women. Colorectal cancer develops as a result of mutations in genes that control proliferation and cell death. It was established that in the development of a tumor there is originally a prevascular phase followed by a phase of tumor angiogenesis. In the future it is necessary to develop new clinical protocols that angiogenesis inhibitors are associated with chemo or radiotherapy, conventional or other methods such as immunotherapy and gene therapy.

  5. Angiogenesis Factors Involved in the Pathogenesis of Colorectal Cancer

    PubMed Central

    MIHALACHE, A.; ROGOVEANU, I.

    2014-01-01

    Colorectal cancer stands at the top of oncologic pathology in the world, and in the same measure in Romania because is the third most frequent cancer diagnosed in men and women. Colorectal cancer develops as a result of mutations in genes that control proliferation and cell death. It was established that in the development of a tumor there is originally a prevascular phase followed by a phase of tumor angiogenesis. In the future it is necessary to develop new clinical protocols that angiogenesis inhibitors are associated with chemo or radiotherapy, conventional or other methods such as immunotherapy and gene therapy. PMID:24791198

  6. Melatonin, an inhibitory agent in breast cancer.

    PubMed

    Nooshinfar, Elaheh; Safaroghli-Azar, Ava; Bashash, Davood; Akbari, Mohammad Esmaeil

    2017-01-01

    The heterogeneous nature of breast cancer makes it one of the most challenging cancers to treat. Due to the stimulatory effect of estrogen in mammary cancer progression, anti-estrogenic agents like melatonin have found their way into breast cancer treatment. Further studies confirmed a reverse correlation between nocturnal melatonin levels and the development of mammary cancer. In this study we reviewed the molecular inhibitory effects of melatonin in breast cancer therapy. To open access the articles, Google scholar and science direct were used as a motor search. We used from valid external and internal databases. To reach the search formula, we determined mean key words like breast cancer, melatonin, cell proliferation and death. To retrieval the related articles, we continuously search the articles from 1984 to 2015. The relevance and the quality of the 480 articles were screened; at least we selected 80 eligible articles about melatonin molecular mechanism in breast cancer. The results showed that melatonin not only inhibits breast cancer cell growth, but also is capable of inhibiting angiogenesis, cancer cell invasion, and telomerase activity. Interestingly this hormone is able to induce apoptosis through the suppression or induction of a wide range of signaling pathways. Moreover, it seems that the concomitant administration of melatonin with other conventional chemotherapy agents had beneficial effects for patients with breast cancer, by alleviating unfavorable effects of those agents and enhancing their efficacy. The broad inhibitory effects of melatonin in breast cancer make it a promising agent and may add it to the list of potential drugs in treatment of this cancer.

  7. Chemokines: novel targets for breast cancer metastasis

    PubMed Central

    Ali, Simi; Lazennec, Gwendal

    2007-01-01

    Recent studies have highlighted the possible involvement of chemokines and their receptors in breast cancer progression and metastasis. Chemokines and their receptors constitute a superfamily of signalling factors whose prognosis value in breast cancer progression remains unclear. We will examine here the expression pattern of chemokines and their receptors in mammary gland physiology and carcinogenesis. The nature of the cells producing chemokines or harboring chemokine receptors appears to be crucial in certain conditions for example, the infiltration of the primary tumor by leukocytes and angiogenesis. In addition, chemokines, their receptors and the interaction with glycosaminoglycan (GAGs) are key players in the homing of cancer cells to distant metastasis sites. Several lines of evidence, including in vitro and in vivo models, suggest that the mechanism of action of chemokines in cancer development involves the modulation of proliferation, apoptosis, invasion, leukocyte recruitment or angiogenesis. Furthermore, we will discuss the regulation of chemokine network in tumor neovascularity by decoy receptors. The reasons accounting for the deregulation of chemokines and chemokine receptors expression in breast cancer are certainly crucial for the comprehension of chemokine role in breast cancer and are in several cases linked to estrogen receptor status. The targeting of chemokines and chemokine receptors by antibodies, small molecule antagonists, viral chemokine binding proteins and heparins appears as promising tracks to develop therapeutic strategies. Thus there is significant interest in developing strategies to antagonize the chemokine function, and an opportunity to interfere with metastasis, the leading cause of death in most patients. PMID:17717637

  8. Carboplatin and Eribulin Mesylate in Triple Negative Breast Cancer Patients

    ClinicalTrials.gov

    2016-06-30

    Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Male Breast Cancer; Progesterone Receptor-negative 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; Triple-negative Breast Cancer

  9. Mitochondrial activation by inhibition of PDKII suppresses HIF1a signaling and angiogenesis in cancer.

    PubMed

    Sutendra, G; Dromparis, P; Kinnaird, A; Stenson, T H; Haromy, A; Parker, J M R; McMurtry, M S; Michelakis, E D

    2013-03-28

    Most solid tumors are characterized by a metabolic shift from glucose oxidation to glycolysis, in part due to actively suppressed mitochondrial function, a state that favors resistance to apoptosis. Suppressed mitochondrial function may also contribute to the activation of hypoxia-inducible factor 1α (HIF1α) and angiogenesis. We have previously shown that the inhibitor of pyruvate dehydrogenase kinase (PDK) dichloroacetate (DCA) activates glucose oxidation and induces apoptosis in cancer cells in vitro and in vivo. We hypothesized that DCA will also reverse the 'pseudohypoxic' mitochondrial signals that lead to HIF1α activation in cancer, even in the absence of hypoxia and inhibit cancer angiogenesis. We show that inhibition of PDKII inhibits HIF1α in cancer cells using several techniques, including HIF1α luciferase reporter assays. Using pharmacologic and molecular approaches that suppress the prolyl-hydroxylase (PHD)-mediated inhibition of HIF1α, we show that DCA inhibits HIF1α by both a PHD-dependent mechanism (that involves a DCA-induced increase in the production of mitochondria-derived α-ketoglutarate) and a PHD-independent mechanism, involving activation of p53 via mitochondrial-derived H(2)O(2), as well as activation of GSK3β. Effective inhibition of HIF1α is shown by a decrease in the expression of several HIF1α regulated gene products as well as inhibition of angiogenesis in vitro in matrigel assays. More importantly, in rat xenotransplant models of non-small cell lung cancer and breast cancer, we show effective inhibition of angiogenesis and tumor perfusion in vivo, assessed by contrast-enhanced ultrasonography, nuclear imaging techniques and histology. This work suggests that mitochondria-targeting metabolic modulators that increase pyruvate dehydrogenase activity, in addition to the recently described pro-apoptotic and anti-proliferative effects, suppress angiogenesis as well, normalizing the pseudo-hypoxic signals that lead to normoxic HIF1

  10. Breast cancer statistics, 2011.

    PubMed

    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.

  11. Angiogenesis in Schistosoma haematobium-associated urinary bladder cancer.

    PubMed

    Dematei, Anderson; Fernandes, Rúben; Soares, Raquel; Alves, Helena; Richter, Joachim; Botelho, Monica C

    2017-09-28

    Schistosoma haematobium, a parasitic flatworm that infects more than 100 million people, mostly in the developing world, is the causative agent of urogenital schistosomiasis, and is associated with a high incidence of squamous cell carcinoma (SCC) of the bladder. During infection, eggs are deposited in the bladder causing an intense inflammatory reaction. Angiogenesis is defined as the formation of new blood vessels from preexisting ones and is recognized as a key event in cell proliferation and carcinogenesis and spread of malignant lesions. A growing amount of evidence points to angiogenesis playing a key role in schistosomiasis-associated bladder cancer. Thus, identifying biomarkers of this process plays an important role in the study of cancer. Here, we review recent findings on the role of angiogenesis in bladder cancer and the growth factors that induce and assist in their development, particularly SCC of the bladder associated to urogenital schistosomiasis. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  12. BREAST CANCER AND EXERCISE

    ClinicalTrials.gov

    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.

  13. Global breast cancer seasonality.

    PubMed

    Oh, Eun-Young; Ansell, Christine; Nawaz, Hamayun; Yang, Chul-Ho; Wood, Patricia A; Hrushesky, William J M

    2010-08-01

    Human breast cancer incidence has seasonal patterns that seem to vary among global populations. The aggregate monthly frequency of breast cancer diagnosis was collected and examined for 2,921,714 breast cancer cases diagnosed across 64 global regions over spans from 2 to 53 years. Breast cancer is consistently diagnosed more often in spring and fall, both in the Northern and Southern Hemispheres, regardless of presumable menopausal status (50). This seasonality is increasingly more prominent as population distance from the equator increases and this latitude dependence is most pronounced among women living in rural areas. Moreover, the overall annual incidence (2005-2006), per 100,000 population, of breast cancer increased as the latitude of population residence increased. These data make it clear that human breast cancer discovery occurs non-randomly throughout each year with peaks near both equinoxes and valleys near both solstices. This stable global breast cancer seasonality has implications for better prevention, more accurate screening, earlier diagnosis, and more effective treatment. This complex latitude-dependent breast cancer seasonality is clearly related to predictable local day/night length changes which occur seasonally. Its mechanism may depend upon seasonal sunlight mediation of vitamin D and seasonal mediation of nocturnal melatonin peak level and duration.

  14. Synchronous bilateral breast cancer in a male

    PubMed Central

    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

  15. The Role of Vascular Endothelial Growth Factor A Polymorphisms in Breast Cancer

    PubMed Central

    Sa-nguanraksa, Doonyapat; O-charoenrat, Pornchai

    2012-01-01

    Breast cancer is the most common cancer in females and the leading cause of cancer death in women worldwide. Angiogenesis, the formation of new blood vessels, plays an important role in the development and progression of breast cancer. Vascular endothelial growth factor A (VEGFA), the key modulator of angiogenesis, is highly expressed in cancer tissue and correlates with its more aggressive features. Polymorphisms of VEGFA alter the levels of expression and subsequently influence the susceptibility and aggressiveness of breast cancer. Assessment of VEGFA polymorphisms may be used for the identification of patients suitable for anti-VEGFA therapy. PMID:23203097

  16. The role of vascular endothelial growth factor a polymorphisms in breast cancer.

    PubMed

    Sa-Nguanraksa, Doonyapat; O-Charoenrat, Pornchai

    2012-11-13

    Breast cancer is the most common cancer in females and the leading cause of cancer death in women worldwide. Angiogenesis, the formation of new blood vessels, plays an important role in the development and progression of breast cancer. Vascular endothelial growth factor A (VEGFA), the key modulator of angiogenesis, is highly expressed in cancer tissue and correlates with its more aggressive features. Polymorphisms of VEGFA alter the levels of expression and subsequently influence the susceptibility and aggressiveness of breast cancer. Assessment of VEGFA polymorphisms may be used for the identification of patients suitable for anti-VEGFA therapy.

  17. Recent molecular discoveries in angiogenesis and antiangiogenic therapies in cancer.

    PubMed

    Welti, Jonathan; Loges, Sonja; Dimmeler, Stefanie; Carmeliet, Peter

    2013-08-01

    Four decades ago, angiogenesis was recognized as a therapeutic target for blocking cancer growth. Because of its importance, VEGF has been at the center stage of antiangiogenic therapy. Now, several years after FDA approval of an anti-VEGF antibody as the first antiangiogenic agent, many patients with cancer and ocular neovascularization have benefited from VEGF-targeted therapy; however, this anticancer strategy is challenged by insufficient efficacy, intrinsic refractoriness, and resistance. Here, we examine recent discoveries of new mechanisms underlying angiogenesis, discuss successes and challenges of current antiangiogenic therapy, and highlight emerging antiangiogenic paradigms.

  18. CDC Vital Signs: Breast Cancer

    MedlinePlus

    ... 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 ...

  19. Stages of Male Breast Cancer

    MedlinePlus

    ... spread outside the breast . In stage IB , small clusters of breast cancer cells (larger than 0.2 ... centimeters but not larger than 5 centimeters. Small clusters of breast cancer cells (larger than 0.2 ...

  20. Copper and angiogenesis : unraveling a relationship key to cancer progression.

    SciTech Connect

    Finney, L. F.; Vogt, S. V.; Fukai, TF; Glesne, DG; Univ. of Illinois at Chicago

    2009-01-01

    Angiogenesis, the formation of new capillaries from existing vasculature, is a critical process in normal physiology as well as several physiopathologies. A desire to curb the supportive role angiogenesis plays in the development and metastasis of cancers has driven exploration into anti-angiogenic strategies as cancer therapeutics. Key to this, angiogenesis additionally displays an exquisite sensitivity to bioavailable copper. Depletion of copper has been shown to inhibit angiogenesis in a wide variety of cancer cell and xenograft systems. Several clinical trials using copper chelation as either an adjuvant or primary therapy have been conducted. Yet, the biological basis for the sensitivity of angiogenesis remains unclear. Numerous molecules important to angiogenesis regulation have been shown to be either directly or indirectly influenced by copper, yet a clear probative answer to the connection remains elusive. Measurements of copper in biological systems have historically relied on techniques that, although demonstrably powerful, provide little or no information as to the spatial distribution of metals in a cellular context. Therefore, several new approaches have been developed to image copper in a biological context. One such approach relies on synchrotron-derived X-rays from third-generation synchrotrons and the technique of high resolution X-ray fluorescence microprobe (XFM) analysis. Recent applications of XFM approaches to the role of copper in regulating angiogenesis have provided unique insight into the connection between copper and cellular behaviour. Using XFM, copper has been shown to be highly spatially regulated, as it is translocated from perinuclear areas of the cell towards the tips of extending filopodia and across the cell membrane into the extracellular space during angiogenic processes. Such findings may explain the heightened sensitivity of this cellular process to this transition metal and set a new paradigm for the kinds of regulatory

  1. Copper and angiogenesis : unravelling a relationship key to cancer progression.

    SciTech Connect

    Finney, L. A.; Vogt, S.; Fukai, T.; Glesne, D.; Univ. of Illinois

    2009-01-01

    Angiogenesis, the formation of new capillaries from existing vasculature, is a critical process in normal physiology as well as several physiopathologies. A desire to curb the supportive role angiogenesis plays in the development and metastasis of cancers has driven exploration into anti-angiogenic strategies as cancer therapeutics. Key to this, angiogenesis additionally displays an exquisite sensitivity to bioavailable copper. Depletion of copper has been shown to inhibit angiogenesis in a wide variety of cancer cell and xenograft systems. Several clinical trials using copper chelation as either an adjuvant or primary therapy have been conducted. Yet, the biological basis for the sensitivity of angiogenesis remains unclear. Numerous molecules important to angiogenesis regulation have been shown to be either directly or indirectly influenced by copper, yet a clear probative answer to the connection remains elusive. Measurements of copper in biological systems have historically relied on techniques that, although demonstrably powerful, provide little or no information as to the spatial distribution of metals in a cellular context. Therefore, several new approaches have been developed to image copper in a biological context. One such approach relies on synchrotron-derived X-rays from third-generation synchrotrons and the technique of high resolution X-ray fluorescence microprobe (XFM) analysis. Recent applications of XFM approaches to the role of copper in regulating angiogenesis have provided unique insight into the connection between copper and cellular behaviour. Using XFM, copper has been shown to be highly spatially regulated, as it is translocated from perinuclear areas of the cell towards the tips of extending filopodia and across the cell membrane into the extracellular space during angiogenic processes. Such findings may explain the heightened sensitivity of this cellular process to this transition metal and set a new paradigm for the kinds of regulatory

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

    DTIC Science & Technology

    2006-07-01

    the Witness model will be tailored for breast cancer survivors and the peer interventionists (breast cancer survivors and lay health advisors) will be...by a lay health advisor; 4) discussion of concerns and myths about breast cancer and screening /surveillance that are prevalent among AAW; 5) review...Breast cancer screening surveillance Breast cancer screening Treatment/Time of Treatment intention /adherence & physician recommendation

  3. Breast Cancer and Bone Loss

    MedlinePlus

    ... 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 ...

  4. Adipose tissue and breast cancer progression: a link between metabolism and cancer.

    PubMed

    Bertolini, Francesco

    2013-08-01

    Obesity, an excess accumulation of adipose tissue occurring in mammalians when caloric intake exceeds energy expenditure, is associated with an increased incidence, morbidity and mortality from several types of neoplastic diseases including postmenopausal breast cancer. Several investigators have recently studied the role of human white adipose tissue (WAT) progenitors in preclinical models of breast cancer. WAT progenitors were found to promote breast cancer local growth, angiogenesis, EMT, migration and metastatic spreading. Breast cancer patients with intraepithelial neoplasia who received autologous WAT cells for breast reconstruction after surgical removal of breast cancer showed an increased risk of recurrence of local events when compared to controls. There is an urgent need for a better understanding of the role of WAT progenitors in breast cancer local and metastatic growth. A rigorous cancer screening and follow-up of patients enrolled for WAT progenitor-based therapies should be implemented. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Abortion, Miscarriage, and Breast Cancer Risk

    MedlinePlus

    ... Cancers Breast Cancer Screening Research Abortion, Miscarriage, and Breast Cancer Risk: 2003 Workshop In February 2003, the National ... the development of breast cancer. Important Information about Breast Cancer Risk Factors At present, the factors known to ...

  6. Breast cancer and depression.

    PubMed

    Somerset, Wendy; Stout, Steven C; Miller, Andrew H; Musselman, Dominique

    2004-07-01

    Major depression and depressive symptoms, although commonly encountered in patients with medical illnesses, are frequently underdiagnosed and undertreated in women with breast cancer. Depression and its associated symptoms diminish quality of life, adversely affect compliance with medical therapies, and reduce survival. Treatment of depression in women with breast cancer improves their dysphoria and other depressive symptoms, enhances quality of life, and may increase longevity. In this review, studies that investigate pathophysiologic alterations in patients with cancer and comorbid depression are discussed, and the few studies on treatment of depression and related symptoms in women with breast cancer are examined.

  7. Leptin–cytokine crosstalk in breast cancer

    PubMed Central

    Newman, Gale; Gonzalez-Perez, Ruben Rene

    2013-01-01

    Despite accumulating evidence suggesting a positive correlation between leptin levels, obesity, post-menopause and breast cancer incidence, our current knowledge on the mechanisms involved in these relationships is still incomplete. Since the cloning of leptin in 1994 and its receptor (OB-R) 1 year later by Friedman’s laboratory (Zhang et al., 1994) and Tartaglia et al. (Tartaglia et al., 1995), respectively, more than 22,000 papers related to leptin functions in several biological systems have been published (Pubmed, 2012). The ob gene product, leptin, is an important circulating signal for the regulation of body weight. Additionally, leptin plays critical roles in the regulation of glucose homeostasis, reproduction, growth and the immune response. Supporting evidence for leptin roles in cancer has been shown in more than 1000 published papers, with almost 300 papers related to breast cancer (Pubmed, 2012). Specific leptin-induced signaling pathways are involved in the increased levels of inflammatory, mitogenic and pro-angiogenic factors in breast cancer. In obesity, a mild inflammatory condition, deregulated secretion of proinflammatory cytokines and adipokines such as IL-1, IL-6, TNF-α and leptin from adipose tissue, inflammatory and cancer cells could contribute to the onset and progression of cancer. We used an in silico software program, Pathway Studio 9, and found 4587 references citing these various interactions. Functional crosstalk between leptin, IL-1 and Notch signaling (NILCO) found in breast cancer cells could represent the integration of developmental, proinflammatory and pro-angiogenic signals critical for leptin-induced breast cancer cell proliferation/migration, tumor angiogenesis and breast cancer stem cells (BCSCs). Remarkably, the inhibition of leptin signaling via leptin peptide receptor antagonists (LPrAs) significantly reduced the establishment and growth of syngeneic, xenograft and carcinogen-induced breast cancer and, simultaneously

  8. Women with Disabilities and Breast Cancer Screening

    MedlinePlus

    ... and Reasonable Accommodations (RA) Women with Disabilities and Breast Cancer Screening Recommend on Facebook Tweet Share Compartir Finding Breast Cancer Early Can Save Lives Disabilities & Breast Cancer Screening ...

  9. Breast reconstruction after breast cancer.

    PubMed

    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.

  10. Identifying Breast Cancer Oncogenes

    DTIC Science & Technology

    2011-10-01

    which is a study of 3131 human tumor samples and cancer cell lines including 243 breast samples. Tumorscape showed that PAK1 is located in an...chromosome 11q of human tumor samples and cancer cell lines that exhibit highest level of PAK1 amplification divided according to cancer type...breast, non-small cell (NSC) lung, ovarian (Ov), small cell lung (SCL), melanoma (Mel) and esophageal squamous (Esq). PAK1 and CCND1 1oci are marked . B

  11. Oxalate induces breast cancer.

    PubMed

    Castellaro, Andrés M; Tonda, Alfredo; Cejas, Hugo H; Ferreyra, Héctor; Caputto, Beatriz L; Pucci, Oscar A; Gil, German A

    2015-10-22

    Microcalcifications can be the early and only presenting sign of breast cancer. One shared characteristic of breast cancer is the appearance of mammographic mammary microcalcifications that can routinely be used to detect breast cancer in its initial stages, which is of key importance due to the possibility that early detection allows the application of more conservative therapies for a better patient outcome. The mechanism by which mammary microcalcifications are formed is still largely unknown but breast cancers presenting microcalcifications are more often associated with a poorer prognosis. We combined Capillary Electrochromatography, histology, and gene expression (qRT-PCR) to analyze patient-matched normal breast tissue vs. breast tumor. Potential carcinogenicity of oxalate was tested by its inoculation into mice. All data were subjected to statistical analysis. To study the biological significance of oxalates within the breast tumor microenvironment, we measured oxalate concentration in both human breast tumor tissues and adjoining non-pathological breast tissues. We found that all tested breast tumor tissues contain a higher concentration of oxalates than their counterpart non-pathological breast tissue. Moreover, it was established that oxalate induces proliferation of breast cells and stimulates the expression of a pro-tumorigenic gene c-fos. Furthermore, oxalate generates highly malignant and undifferentiated tumors when it was injected into the mammary fatpad in female mice, but not when injected into their back, indicating that oxalate does not induce cancer formation in all types of tissues. Moreover, neither human kidney-epithelial cells nor mouse fibroblast cells proliferate when are treated with oxalate. We found that the chronic exposure of breast epithelial cells to oxalate promotes the transformation of breast cells from normal to tumor cells, inducing the expression of a proto-oncogen as c-fos and proliferation in breast cancer cells

  12. Bone marrow-derived mesenchymal stem cells promote growth and angiogenesis of breast and prostate tumors

    PubMed Central

    2013-01-01

    Introduction Mesenchymal stem cells (MSCs) are known to migrate to tumor tissues. This behavior of MSCs has been exploited as a tumor-targeting strategy for cell-based cancer therapy. However, the effects of MSCs on tumor growth are controversial. This study was designed to determine the effect of MSCs on the growth of breast and prostate tumors. Methods Bone marrow-derived MSCs (BM-MSCs) were isolated and characterized. Effects of BM-MSCs on tumor cell proliferation were analyzed in a co-culture system with mouse breast cancer cell 4T1 or human prostate cancer cell DU145. Tumor cells were injected into nude mice subcutaneously either alone or coupled with BM-MSCs. The expression of cell proliferation and angiogenesis-related proteins in tumor tissues were immunofluorescence analyzed. The angiogenic effect of BM-MSCs was detected using a tube formation assay. The effects of the crosstalk between tumor cells and BM-MSCs on expression of angiogenesis related markers were examined by immunofluorescence and real-time PCR. Results Both co-culturing with mice BM-MSCs (mBM-MSCs) and treatment with mBM-MSC-conditioned medium enhanced the growth of 4T1 cells. Co-injection of 4T1 cells and mBM-MSCs into nude mice led to increased tumor size compared with injection of 4T1 cells alone. Similar experiments using DU145 cells and human BM-MSCs (hBM-MSCs) instead of 4T1 cells and mBM-MSCs obtained consistent results. Compared with tumors induced by injection of tumor cells alone, the blood vessel area was greater in tumors from co-injection of tumor cells with BM-MSCs, which correlated with decreased central tumor necrosis and increased tumor cell proliferation. Furthermore, both conditioned medium from hBM-MSCs alone and co-cultures of hBM-MSCs with DU145 cells were able to promote tube formation ability of human umbilical vein endothelial cells. When hBM-MSCs are exposed to the DU145 cell environment, the expression of markers associated with neovascularization (macrophage

  13. Docosahexaenoic Acid in Preventing Recurrence in Breast Cancer Survivors

    ClinicalTrials.gov

    2016-06-20

    Benign Breast Neoplasm; Ductal Breast Carcinoma In Situ; Invasive Breast Carcinoma; Lobular Breast Carcinoma In Situ; Paget Disease of the Breast; 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

  14. Targeting Breast Cancer Metastasis

    PubMed Central

    Jin, Xin; Mu, Ping

    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 metastatic traits that contribute to the metastasis cascade of breast cancer, which may provide novel avenues for therapeutic targeting. PMID:26380552

  15. Breast Cancer in Young Women

    MedlinePlus

    ... 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 ...

  16. Broccoli Sprout Extract in Treating Patients With Breast Cancer

    ClinicalTrials.gov

    2017-02-14

    Ductal Breast Carcinoma; Ductal Breast Carcinoma In Situ; Estrogen Receptor Negative; Estrogen Receptor Positive; Invasive Breast Carcinoma; Lobular Breast Carcinoma; Postmenopausal; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

  17. Alpha-v Integrin Targeted PET Imaging of Breast Cancer Angiogenesis and Low-Dose Metronomic Anti-Angiogenic Chemotherapy Efficacy

    DTIC Science & Technology

    2008-08-01

    Moderate therapeutic efficacy of positron emission tomography-navigated repetitive transcranial magnetic stimulation for chronic tinnitus: a...the management of stage I and II non-small- cell lung cancer. J Clin Oncol. 2004;22:2357–2362. 14. Higgins JPT, Green S. Cochrane handbook for

  18. Breast Cancer In Women

    Cancer.gov

    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.

  19. Breast size, handedness and breast cancer risk.

    PubMed

    Hsieh, C C; Trichopoulos, D

    1991-01-01

    Bra cup size and handedness were studied as possible risk factors for breast cancer. Data for 3918 cases and 11,712 controls from 7 centres were used to examine the association of handedness with laterality of breast cancer; data for 2325 cases and 7008 controls from 4 centres were used to assess the relation of bra cup size to breast cancer risk. There was a suggestive (P about 0.10) association of handedness with breast cancer laterality: odds ratio of a left-handed (or ambidextrous) woman having a left-sided cancer 1.22 (95% CI 0.96-1.56). Handedness may affect the lateral occurrence of breast cancer, although this tumour is in general more common in the left breast, possibly because this breast is usually slightly larger. Premenopausal women who do not wear bras had half the risk of breast cancer compared with bra users (P about 0.09), possibly because they are thinner and likely to have smaller breasts. Among bra users, larger cup size was associated with an increased risk of breast cancer (P about 0.026), although the association was found only among postmenopausal women and was accounted for, in part, by obesity. These data suggest that bra cup size (and conceivably mammary gland size) may be a risk factor for breast cancer.

  20. Quiz: How much do you know about breast cancer? | NIH MedlinePlus the Magazine

    MedlinePlus

    ... breast cancer late stage breast cancer locally advanced breast cancer Stage III breast cancer is early stage breast cancer late stage breast cancer locally advanced breast cancer Stage IV breast cancer is early stage breast cancer ...

  1. Chemoprevention of Breast Cancer by Dietary Polyphenols.

    PubMed

    Mocanu, Maria-Magdalena; Nagy, Péter; Szöllősi, János

    2015-12-17

    The review will discuss in detail the effects of polyphenols on breast cancer, including both the advantages and disadvantages of the applications of these natural compounds. First, we focus on the characterization of the main classes of polyphenols and then on in vitro and in vivo experiments carried out in breast cancer models. Since the therapeutic effects of the administration of a single type of polyphenol might be limited because of the reduced bioavailability of these drugs, investigations on combination of several polyphenols or polyphenols with conventional therapy will also be discussed. In addition, we present recent data focusing on clinical trials with polyphenols and new approaches with nanoparticles in breast cancer. Besides the clinical and translational findings this review systematically summarizes our current knowledge about the molecular mechanisms of anti-cancer effects of polyphenols, which are related to apoptosis, cell cycle regulation, plasma membrane receptors, signaling pathways and epigenetic mechanisms. At the same time the effects of polyphenols on primary tumor, metastasis and angiogenesis in breast cancer are discussed. The increasing enthusiasm regarding the combination of polyphenols and conventional therapy in breast cancer might lead to additional efforts to motivate further research in this field.

  2. Imaging Cancer Angiogenesis and Metastasis in a Zebrafish Embryo Model.

    PubMed

    Tulotta, C; He, S; van der Ent, W; Chen, L; Groenewoud, A; Spaink, H P; Snaar-Jagalska, B E

    2016-01-01

    Tumor angiogenesis and metastasis are key steps of cancer progression. In vitro and animal model studies have contributed to partially elucidating the mechanisms involved in these processes and in developing therapies. Besides the improvements in fundamental research and the optimization of therapeutic regimes, cancer still remains a major health threatening condition and therefore the development of new models is needed. The zebrafish is a powerful tool to study tumor angiogenesis and metastasis, because it allows the visualization of fluorescently labelled tumor cells inducing vessel remodeling, disseminating and invading surrounding tissues in a whole transparent embryo. The embryo model has also been used to address the contribution of the tumor stroma in sustaining tumor angiogenesis and spreading. Simultaneously, new anti-angiogenic drugs and compounds affecting malignant cell survival and migration can be tested by simply adding the compound into the water of living embryos. Therefore the zebrafish model offers the opportunity to gain more knowledge on cancer angiogenesis and metastasis in vivo with the final aim of providing new translational insights into therapeutic approaches to help patients.

  3. [Remodeling of angiogenesis and lymphangiogenesis in cervical cancer development].

    PubMed

    Kurmyshkina, O V; Belova, L L; Kovchur, P I; Volkova, T O

    2015-01-01

    Ability to stimulate angiogenesis/lymphangiogenesis is recognized as an inherent feature of cancer cells providing necessary conditions for their growth and dissemination. "Angiogenic switch" is one of the earliest consequences of malignant transformation that encompasses a great number of genes and triggers a complex set of signaling cascades in endothelial cells. The processes of tumor microvasculature development are closely connected to the steps of carcinogenesis (from benign lesions to invasive forms) and occur through multiple deviations from the norm. Analysis of expression of proangiogenic factors at successive steps of cervical cancer development (intraepithelial neoplasia, cancer in situ, microinvasive, and invasive cancer) enables to reconstruct the regulatory mechanisms of (lymph-)angiogenesis and to discriminate the most important components. This review presents detailed analysis of literature data on expression of the key regulators of angiogenesis in cervical intraepithelial neoplasia and cervical cancer. Their possible involvement in molecular mechanisms of neoplastic transformation of epithelial cells, as well as invasion and tumor metastasis is discussed. Correlation between expression of proangiogenic molecular factors and various clinicopathological parameters is considered, the potential of their use in molecular diagnostics and targeted therapy of cervical cancer is reviewed. Particular attention is paid to relatively poorly studied regulators of lymphangiogenesis and "non-VEGF dependent", or alternative, angiogenic pathways that constitute the prospect of future research in the field.

  4. Eriocalyxin B, a natural diterpenoid, inhibited VEGF-induced angiogenesis and diminished angiogenesis-dependent breast tumor growth by suppressing VEGFR-2 signaling

    PubMed Central

    Zhou, Xunian; Yue, Grace Gar-Lee; Liu, Minghua; Zuo, Zhili; Lee, Julia Kin-Ming; Li, Mingyue; Tsui, Stephen Kwok-Wing; Fung, Kwok-Pui; Sun, Handong; Pu, Jianxin; Lau, Clara Bik-San

    2016-01-01

    Eriocalyxin B (EriB), a natural ent-kaurane diterpenoid isolated from the plant Isodon eriocalyx var. laxiflora, has emerged as a promising anticancer agent. The effects of EriB on angiogenesis were explored in the present study. Here we demonstrated that the subintestinal vein formation was significantly inhibited by EriB treatment (10, 15 μM) in zebrafish embryos, which was resulted from the alteration of various angiogenic genes as shown in transcriptome profiling. In human umbilical vein endothelial cells, EriB treatment (50, 100 nM) could significantly block vascular endothelial growth factors (VEGF)-induced cell proliferation, tube formation, cell migration and cell invasion. Furthermore, EriB also caused G1 phase cell cycle arrest which was correlated with the down-regulation of the cyclin D1 and CDK4 leading to the inhibition of phosphorylated retinoblastoma protein expression. Investigation of the signal transduction revealed that EriB inhibited VEGF-induced phosphorylation of VEGF receptor-2 via the interaction with the ATP-binding sites according to the molecular docking simulations. The suppression of VEGFR-2 downstream signal transduction cascades was also observed. EriB was showed to inhibit new blood vessel formation in Matrigel plug model and mouse 4T1 breast tumor model. EriB (5 mg/kg/day) treatment was able to decrease tumor vascularization and suppress tumor growth and angiogenesis. Taken together, our findings suggested that EriB is a novel inhibitor of angiogenesis through modulating VEGFR-2 signaling pathway, which could be developed as a promising anti-angiogenic agent for treatment of angiogenesis-related human diseases, such as cancer. PMID:27756875

  5. Cutaneous manifestations of breast cancer.

    PubMed

    Tan, Antoinette R

    2016-06-01

    Breast cancer may present with cutaneous symptoms. The skin manifestations of breast cancer are varied. Some of the more common clinical presentations of metastatic cutaneous lesions from breast cancer will be described. Paraneoplastic cutaneous dermatoses have been reported as markers of breast malignancy and include erythema gyratum repens, acquired ichthyosis, dermatomyositis, multicentric reticulohistiocytosis, and hypertrichosis lanuginosa acquisita. Mammary Paget's disease, often associated with an underlying breast cancer, and Cowden syndrome, which has an increased risk of breast malignancy, each have specific dermatologic findings. Recognition of these distinct cutaneous signs is important in the investigation of either newly diagnosed or recurrent breast cancer.

  6. Stages of Breast Cancer

    MedlinePlus

    ... in lymph and help fight infection and disease. Clusters of lymph nodes are found near the breast ... the tumor is 2 centimeters or smaller. Small clusters of cancer cells (larger than 0.2 millimeter ...

  7. Breast Cancer Treatment

    MedlinePlus

    ... in lymph and help fight infection and disease. Clusters of lymph nodes are found near the breast ... the tumor is 2 centimeters or smaller. Small clusters of cancer cells (larger than 0.2 millimeter ...

  8. Breast Cancer in Men

    MedlinePlus

    ... men may have radiation after surgery. Since most breast cancers in men are hormone receptor-positive, hormone therapy (with tamoxifen) is often used depending on the stage. Chemotherapy may be given before tamoxifen. For men ...

  9. Obesity and Breast Cancer.

    PubMed

    Fortner, Renée T; Katzke, Verena; Kühn, Tilman; Kaaks, Rudolf

    The relationship between adiposity and breast cancer risk and prognosis is complex, with associations that differ depending on when body size is assessed (e.g., pre- vs. postmenopausal obesity) and when breast cancer is diagnosed (i.e., pre- vs. postmenopausal disease). Further, the impact of obesity on risk differs by tumor hormone receptor status (e.g., estrogen (ER) and progesterone (PR) receptor) and, among postmenopausal women, use of exogenous hormones (i.e., hormone replacement therapy (HRT)). In the context of these complexities, this review focuses on associations between childhood and adolescent adiposity, general adiposity, weight changes (i.e., loss and gain), abdominal adiposity, and breast cancer risk and survival. Finally, we discuss potential mechanisms linking adiposity to breast cancer.

  10. The breast cancer conundrum.

    PubMed

    Adams, Patrick

    2013-09-01

    For decades, rates of breast cancer have been going up faster in rich countries than in poor ones. Scientists are beginning to understand more about its causes but unanswered questions remain. Patrick Adams reports.

  11. Breast Cancer - Multiple Languages

    MedlinePlus

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Breast Cancer URL of this page: https://medlineplus.gov/languages/breastcancer.html Other topics A-Z Expand Section ...

  12. Alpha-V Integrin Targeted PET Imagining of Breast Cancer Angiogenesis and Lose-Dose Metronomic Anti-Angiogenic Chemotherapy Efficacy

    DTIC Science & Technology

    2005-08-01

    radiation close estimates, tumour imaging and radionuclide therapy. Int I Cancer. 90: B/ocon/tozte Chem. 15:61-69. 186-198. 1171 Ogawa M, Hatano K, Oishi 5 ...and multimeric RGD peptides would be better than that of monomeric RGD peptide based upon polyvalency (1- 5 ). The receptor binding of the one RGD...min for the tumor. No defluoridation of [18F]FRGD2 was observed. Blood Urine Liver 0 5 10 15 20 0 5 10 15 20 0 5 10 15 20 Time (min) Time (rin) Time

  13. Targeting Angiogenesis in Colorectal Cancer: Tyrosine Kinase Inhibitors.

    PubMed

    Kircher, Sheetal Mehta; Nimeiri, Halla S; Benson, Al B

    2016-01-01

    Colorectal cancer is commonly diagnosed throughout the world, and treatment options have greatly expanded over the last 2 decades. Targeting angiogenesis has been a major focus of study in a variety of malignancy types. Targeting angiogenesis has been achieved by several mechanisms in colorectal cancer, including use of antiangiogenic small molecule tyrosine kinase inhibitors (TKIs). There have been many attempts and failures to prove efficacy of TKIs in the treatment of colorectal cancer including sorafenib, sunitinib, vatalanib, and tivozanib. Regorafenib was the first TKI to demonstrate efficacy and is an orally active inhibitor of angiogenic (including the vascular endothelial growth factor receptors 1, 2, and 3), stromal, and oncogenic receptor tyrosine kinases. There are ongoing investigations of both regorafenib and ninetanib; however, there remains a critical need to better understand novel combinations with TKIs that could prove more efficacious than available options.

  14. Characteristics of invasive breast ductal carcinoma, NOS, diagnosed in a tertiary institution in the East Coast of Malaysia with a focus on tumor angiogenesis.

    PubMed

    Ch'ng, Ewe Seng; Tuan Sharif, Sharifah Emilia; Jaafar, Hasnan

    2012-01-01

    Prognosis of breast cancer depends on classic pathological factors and also tumor angiogenesis. This study aimed to evaluate the clinicopathological factors of breast cancer in a tertiary centre with a focus on the relationship between tumor angiogenesis and clinicopathological factors. Clinicopathological data were retrieved from the archived formal pathology reports for surgical specimens diagnosed as invasive ductal carcinoma, NOS. Microvessels were immunohistochemically stained with anti-CD34 antibody and quantified as microvessel density. At least 50% of 94 cases of invasive breast ductal carcinoma in the study were advanced stage. The majority had poor prognosis factors such as tumor size larger than 50mm (48.9%), positive lymph node metastasis (60.6%), and tumor grade III (52.1%). Higher percentages of estrogen and progesterone receptor negative cases were recorded (46.8% and 46.8% respectively). Her-2 overexpression cases and triple negative breast cancers constituted 24.5% and 22.3% respectively. Significantly higher microvessel density was observed in the younger patient age group (p=0.012). There were no significant associations between microvessel density and other clinicopathological factors (p>0.05). Majority of the breast cancer patients of this institution had advanced stage disease with poorer prognostic factors as compared to other local and western studies. Breast cancer in younger patients might be more proangiogenic.

  15. Paclitaxel targets VEGF-mediated angiogenesis in ovarian cancer treatment

    PubMed Central

    Ai, Bin; Bie, Zhixin; Zhang, Shuai; Li, Ailing

    2016-01-01

    Ovarian cancer is one of the gynecologic cancers with the highest mortality, wherein vascular endothelial growth factor (VEGF) is involved in regulating tumor vascularization, growth, migration, and invasion. VEGF-mediated angiogenesis in tumors has been targeted in various cancer treatments, and anti-VEGF therapy has been used clinically for treatment of several types of cancer. Paclitaxel is a natural antitumor agent in the standard front-line treatment that has significant efficiency to treat advanced cancers, including ovarian cancer. Although platinum/paclitaxel-based chemotherapy has good response rates, most patients eventually relapse because the disease develops drug resistance. We aim to review the recent advances in paclitaxel treatment of ovarian cancer via antiangiogenesis. Single-agent therapy may be used in selected cases of ovarian cancer. However, to prevent drug resistance, drug combinations should be identified for optimal effectiveness and existing therapies should be improved. PMID:27648354

  16. [Trisomy 21 and breast cancer: A genetic abnormality which protects against breast cancer?].

    PubMed

    Martel-Billard, C; Cordier, C; Tomasetto, C; Jégu, J; Mathelin, C

    2016-04-01

    Trisomy 21 (T21) is the most common chromosomal abnormality and one of the main causes of intellectual disability. The tumor profile of T21 patients is characterized by the low frequency of solid tumors including breast cancer. The objective of this work was to analyze the literature to find possible clues for the low frequency of breast cancer in T21 persons with a focus on one hand to the various risks and protective factors against breast cancer for women T21, and on the other hand to changes in the expression of different genes located on chromosome 21. T21 women have hormonal and societal risk factors for breast cancer: frequent nulliparity, lack of breastfeeding, physical inactivity and high body mass index. The age of menopause, earlier in T21 women, has a modest protective effect against breast cancer. The low rate of breast tumors in T21 women is probably mainly linked to the reduced life expectancy compared to the general population (risk of death before the age of onset of the majority of breast cancers) and the presence of a third chromosome 21, characterizing the disease. It might lead to the increased expression of a number of genes contributing directly or undirectly to tumor suppression, decreased tumor angiogenesis and increased cell apoptosis. Moreover, changes in the mammary stroma of persons T21 could have an inhibitory role on the development of breast tumors. The low frequency of breast cancers for T21 patients may not only be explained by hormonal and societal factors, but also by genetic mechanisms which could constitute an interesting axis of research in breast cancer. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. Dietary compounds galangin and myricetin suppress ovarian cancer cell angiogenesis

    PubMed Central

    Huang, Haizhi; Chen, Allen Y.; Rojanasakul, Yon; Ye, Xingqian; Rankin, Gary O.; Chen, Yi Charlie

    2015-01-01

    Galangin and myricetin are flavonoids isolated from vegetables and fruits which exhibit anti-proliferative activity in human cancer cells. In this study, their anti-angiogenic effects were investigated with in vitro (HUVEC) and in vivo (CAM) models, which showed that galangin and myricetin inhibited angiogenesis induced by OVCAR-3 cells. The molecular mechanisms through which galangin and myricetin suppress angiogenesis were also studied. It was observed that galangin and myricetin inhibited secretion of the key angiogenesis mediator vascular endothelial growth factor (VEGF) and decreased levels of p-Akt, p-70S6K and hypoxia-inducible factor-1α (HIF-1α) proteins in A2780/CP70 and OVCAR-3 cells. Transient transfection experiments showed that galangin and myricetin inhibited secretion of VEGF by the Akt/p70S6K/ HIF-1α pathway. Moreover, a novel pathway, p21/HIF-1α/VEGF, was found to be involved in the inhibitory effect of myricetin on angiogenesis in OVCAR-3 cells. These data suggest that galangin and myricetin might serve as potential anti-angiogenic agents in the prevention of ovarian cancers dependent on new blood vessel networks. PMID:26113875

  18. Dietary compounds galangin and myricetin suppress ovarian cancer cell angiogenesis.

    PubMed

    Huang, Haizhi; Chen, Allen Y; Rojanasakul, Yon; Ye, Xingqian; Rankin, Gary O; Chen, Yi Charlie

    2015-05-01

    Galangin and myricetin are flavonoids isolated from vegetables and fruits which exhibit anti-proliferative activity in human cancer cells. In this study, their anti-angiogenic effects were investigated with in vitro (HUVEC) and in vivo (CAM) models, which showed that galangin and myricetin inhibited angiogenesis induced by OVCAR-3 cells. The molecular mechanisms through which galangin and myricetin suppress angiogenesis were also studied. It was observed that galangin and myricetin inhibited secretion of the key angiogenesis mediator vascular endothelial growth factor (VEGF) and decreased levels of p-Akt, p-70S6K and hypoxia-inducible factor-1α (HIF-1α) proteins in A2780/CP70 and OVCAR-3 cells. Transient transfection experiments showed that galangin and myricetin inhibited secretion of VEGF by the Akt/p70S6K/ HIF-1α pathway. Moreover, a novel pathway, p21/HIF-1α/VEGF, was found to be involved in the inhibitory effect of myricetin on angiogenesis in OVCAR-3 cells. These data suggest that galangin and myricetin might serve as potential anti-angiogenic agents in the prevention of ovarian cancers dependent on new blood vessel networks.

  19. Targeting Angiogenesis in Biliary Tract Cancers: An Open Option

    PubMed Central

    Simone, Valeria; Brunetti, Oronzo; Lupo, Luigi; Testini, Mario; Maiorano, Eugenio; Simone, Michele; Longo, Vito; Rolfo, Christian; Peeters, Marc; Scarpa, Aldo; Azzariti, Amalia; Russo, Antonio; Ribatti, Domenico; Silvestris, Nicola

    2017-01-01

    Biliary tract cancers (BTCs) are characterized by a bad prognosis and the armamentarium of drugs for their treatment is very poor. Although the inflammatory status of biliary tract represents the first step in the cancerogenesis, the microenvironment also plays a key role in the pathogenesis of BTCs, promoting tumor angiogenesis, invasion and metastasis. Several molecules, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), are involved in the angiogenesis process and their expression on tumor samples has been explored as prognostic marker in both cholangiocarcinoma and gallbladder cancer. Recent studies evaluated the genomic landscape of BTCs and evidenced that aberrations in several genes enrolled in the pro-angiogenic signaling, such as FGF receptor-2 (FGFR-2), are characteristic of BTCs. New drugs targeting the signaling pathways involved in angiogenesis have been tested in preclinical studies both in vitro and in vivo with promising results. Moreover, several clinical studies tested monoclonal antibodies against VEGF and tyrosine kinase inhibitors targeting the VEGF and the MEK/ERK pathways. Herein, we evaluate both the pathogenic mechanisms of BTCs focused on angiogenesis and the preclinical and clinical data available regarding the use of new anti-angiogenic drugs in these malignancies. PMID:28212293

  20. Targeting Angiogenesis in Biliary Tract Cancers: An Open Option.

    PubMed

    Simone, Valeria; Brunetti, Oronzo; Lupo, Luigi; Testini, Mario; Maiorano, Eugenio; Simone, Michele; Longo, Vito; Rolfo, Christian; Peeters, Marc; Scarpa, Aldo; Azzariti, Amalia; Russo, Antonio; Ribatti, Domenico; Silvestris, Nicola

    2017-02-15

    Biliary tract cancers (BTCs) are characterized by a bad prognosis and the armamentarium of drugs for their treatment is very poor. Although the inflammatory status of biliary tract represents the first step in the cancerogenesis, the microenvironment also plays a key role in the pathogenesis of BTCs, promoting tumor angiogenesis, invasion and metastasis. Several molecules, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), are involved in the angiogenesis process and their expression on tumor samples has been explored as prognostic marker in both cholangiocarcinoma and gallbladder cancer. Recent studies evaluated the genomic landscape of BTCs and evidenced that aberrations in several genes enrolled in the pro-angiogenic signaling, such as FGF receptor-2 (FGFR-2), are characteristic of BTCs. New drugs targeting the signaling pathways involved in angiogenesis have been tested in preclinical studies both in vitro and in vivo with promising results. Moreover, several clinical studies tested monoclonal antibodies against VEGF and tyrosine kinase inhibitors targeting the VEGF and the MEK/ERK pathways. Herein, we evaluate both the pathogenic mechanisms of BTCs focused on angiogenesis and the preclinical and clinical data available regarding the use of new anti-angiogenic drugs in these malignancies.

  1. Human Breast Cancer Histoid

    PubMed Central

    Kaur, Pavinder; Ward, Brenda; Saha, Baisakhi; Young, Lillian; Groshen, Susan; Techy, Geza; Lu, Yani; Atkinson, Roscoe; Taylor, Clive R.; Ingram, Marylou

    2011-01-01

    Progress in our understanding of heterotypic cellular interaction in the tumor microenvironment, which is recognized to play major roles in cancer progression, has been hampered due to unavailability of an appropriate in vitro co-culture model. The aim of this study was to generate an in vitro 3-dimensional human breast cancer model, which consists of cancer cells and fibroblasts. Breast cancer cells (UACC-893) and fibroblasts at various densities were co-cultured in a rotating suspension culture system to establish co-culture parameters. Subsequently, UACC-893, BT.20, or MDA.MB.453 were co-cultured with fibroblasts for 9 days. Co-cultures resulted in the generation of breast cancer histoid (BCH) with cancer cells showing the invasion of fibroblast spheroids, which were visualized by immunohistochemical (IHC) staining of sections (4 µm thick) of BCH. A reproducible quantitative expression of C-erbB.2 was detected in UACC-893 cancer cells in BCH sections by IHC staining and the Automated Cellular Imaging System. BCH sections also consistently exhibited qualitative expression of pancytokeratins, p53, Ki-67, or E-cadherin in cancer cells and that of vimentin or GSTPi in fibroblasts, fibronectin in the basement membrane and collagen IV in the extracellular matrix. The expression of the protein analytes and cellular architecture of BCH were markedly similar to those of breast cancer tissue. PMID:22034518

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

    ClinicalTrials.gov

    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

  3. Preinvasive Breast Cancer

    PubMed Central

    Sgroi, Dennis C.

    2014-01-01

    Preinvasive breast cancer accounts for approximately one-third of all newly diagnosed breast cancer cases in the United States and constitutes a spectrum of neoplastic lesions with varying degrees of differentiation and clinical behavior. High-throughput genetic, epigenetic, and gene-expression analyses have enhanced our understanding of the relationship of these early neoplastic lesions to normal breast tissue, and they strongly suggest that preinvasive breast cancer develops and evolves along two distinct molecular genetic and biological pathways that correlate with tumor grade. Although unique epigenetic and gene-expression changes are not observed in the tumor epithelial compartment during the transition from preinvasive to invasive disease, distinct molecular alterations are observed in the tumor-stromal and myoepithelial cells. This suggests that the stromal and myoepithelial microenvironment of preinvasive breast cancer actively participates in the transition from preinvasive to invasive disease. An improved understanding of the transition from preinvasive to invasive breast cancer will pave the way for novel preventative and therapeutic strategies. PMID:19824828

  4. Gene variants in the angiogenesis pathway and prostate cancer

    PubMed Central

    Amankwah, Ernest K.; Sellers, Thomas A.; Park, Jong Y.

    2012-01-01

    Although the causes of prostate cancer are still unknown, numerous studies support the role of genetic factors in the development and progression of this disease. Single nucleotide polymorphisms (SNPs) in key angiogenesis genes have been studied in prostate cancer. In this review, we provide an overview of the current knowledge of the role of genetic variants in the angiogenesis pathway in prostate cancer risk and progression. Of the 17 prostate cancer genome-wide association studies (GWAS) conducted to date, only one identified disease-associated SNPs in a region of an angiogenesis pathway gene. An association was observed between aggressive disease and three intergenic SNPs (rs11199874, rs10749408 and rs10788165) in a region on chromosome 10q26 that encompasses FGFR2. The majority (27/32, 84.4%) of primary candidate gene studies reviewed had a small (n < 800, 20/32, 62.5%) to medium sample size (n = 800–2000, 7/32, 21.9%), whereas only five (15.6%) had a large sample size (n ≥ 2000). Results from the large studies revealed associations with risk and aggressive disease for SNPs in NOS2A, NOS3 and MMP-2 and risk for HIF1-α. Meta-analyses have so far been conducted on FGFR2, TGF-β, TNF-α, HIF1-α and IL10 and the results reveal an association with risk for SNPs in FGFR2 and TGF-β and aggressive disease for SNPs in IL-10. Thus, existing evidence from GWAS and large candidate gene studies indicates that SNPs from a limited number of angiogenesis pathway genes are associated with prostate cancer risk and progression. PMID:22523086

  5. Reappraising antiangiogenic therapy for breast cancer.

    PubMed

    Kerbel, Robert S

    2011-10-01

    Phase III trials of antiangiogenic drugs for metastatic breast cancer have either had only limited success, e.g. the monoclonal anti-VEGF antibody bevacizumab when used with various conventional chemotherapy regimens, or have failed altogether, e.g. the small molecule oral tyrosine kinase inhibitor (TKI) sunitinib. No phase III trial has yet demonstrated an overall survival benefit and the progression free survival (PFS) benefits, when attained with bevacizumab are short, with perhaps one exception. Together, these results call for a reappraisal of using antiangiogenic drugs for breast cancer and possible strategies to improve their efficacy. Among the reasons to help explain the limited benefits observed thus far include the possibility that angiogenesis may not be a major driver of breast cancer growth, compared to some other types of cancer; that acquired resistance may develop rapidly to VEGF-pathway targeting antiangiogenic drugs, in part due to angiogenic growth factor redundancy; that optimal chemotherapy regimens have not been used in conjunction with an antiangiogenic drug; and that antiangiogenic drugs may secondarily aggravate biologic aggressiveness of the tumors, thereby reducing their overall efficacy after inducing an initial benefit. Several possible strategies are discussed for improving the efficacy of antiangiogenic drugs, including combination with different chemotherapy regimens, e.g. long term and less toxic metronomic chemotherapy protocols; validation of predictive biomarkers to individualize patient therapy; development of improved preclinical therapy models, e.g. involving advanced metastatic breast cancer, and combination with other types of anti-cancer agents especially biologies such as trastuzumab for Her2-positive breast cancer. Reasons for the current concern regarding use of antiangiogenic drug treatments for early stage cancers, including breast cancer, are also discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Viruses and Breast Cancer

    PubMed Central

    Lawson, James S.; Heng, Benjamin

    2010-01-01

    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. PMID:24281093

  7. Expression of the angiogenic factors vascular endothelial cell growth factor, acidic and basic fibroblast growth factor, tumor growth factor beta-1, platelet-derived endothelial cell growth factor, placenta growth factor, and pleiotrophin in human primary breast cancer and its relation to angiogenesis.

    PubMed

    Relf, M; LeJeune, S; Scott, P A; Fox, S; Smith, K; Leek, R; Moghaddam, A; Whitehouse, R; Bicknell, R; Harris, A L

    1997-03-01

    Angiogenesis is a significant prognostic factor in breast cancer, but the factors that control angiogenesis in vivo are not well defined. Multiple angiogenic polypeptides are known, and we have determined the expression of seven of these in primary human breast cancers; the relationship of expression to estrogen receptor and vascular density was also examined. Vascular endothelial growth factor (VEGF) and its four isoforms (121, 165, 189, and 206 amino acids), transforming growth factor (TGF)-beta1, pleiotrophin, acidic and basic fibroblast growth factor (FGF), placental growth factor, and thymidine phosphorylase (platelet-derived endothelial cell growth factor) were quantitated by RNase protection analysis. beta-FGF was also measured by ELISA. The estrogen receptor (ER), epidermal growth factor receptor, and vascular density were analyzed in 64 primary breast cancers. All tumors expressed at least six different vascular growth factors. VEGF was most abundant, and the transcript for the 121-amino acid form predominated. Other angiogenic factors expressed at high levels were thymidine phosphorylase and TGF-beta1. Expression of most of the angiogenic factors did not correlate with that of ER or vascular density. However, thymidine phosphorylase did, with a correlation coefficient of 0.3 (P = 0.03). There were significant associations of pleiotrophin with acidic FGF expression (P = 0.001) and TGF-beta with platelet-derived endothelial cell growth factor expression (P = 0.001). Thus, angiogenesis may involve a coordinate regulation of some vascular growth factors. High VEGF expression correlated with poor prognosis in univariate analysis (P = 0.03), as did ER and epidermal growth factor receptor expression. Basic FGF was also assessed by ELISA and was more highly expressed in tumors than normal breast tissues (median, 346 microg/ml cytosol; range, 54-1323 versus median, 149; range, 32-509; P = 0.01). Implications for therapy are that broad spectrum agents that block

  8. Breast Cancer Detection

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The BioScan System was developed by OmniCorder Technologies, Inc. at the Jet Propulsion Laboratory. The system is able to locate cancerous lesions by detecting the cancer's ability to recruit a new blood supply. A digital sensor detects infrared energy emitted from the body and identifies the minute differences accompanying the blood flow changes associated with cancerous cells. It also has potential use as a monitoring device during cancer treatment. This technology will reduce the time taken to detect cancerous cells and allow for earlier intervention, therefore increasing the overall survival rates of breast cancer patients.

  9. Oral contraceptives and breast cancer.

    PubMed

    Johnson, K H; Millard, P S

    1996-10-01

    The Collaborative Group on Hormonal Factors in Breast Cancer conducted a meta-analysis of data from 10 cohort and 44 case-control studies of the association between combined oral contraceptive (OC) use and breast cancer. 53,297 women with breast cancer and 100,239 women with no breast cancer from 25 countries worldwide were studied. Current OC users faced a 24% increased risk of developing breast cancer (confidence interval = 1.15-1.33). This risk fell steadily after cessation and reached 0 at 10 years and thereafter. Use of OCs with higher doses were associated with a greater risk of breast cancer than medium or low-dose OCs. The number of excess cancers in women while using OCs and up to 10 years after OC cessation stood at 0.5/10,000 women 16-19 years old, 1.5/10,000 women 20-24 years old, and 4.7/10,000 women 25-29 years old. The elevated risk of developing breast cancer did not differ by country of origin, ethnic background, reproductive history, or family history of breast cancer. OC users had less clinically advanced breast cancer than never-users who had breast cancer. This finding plus the moderate reduced risk of breast cancer more than 10 years after OC cessation suggest that OCs may effect earlier diagnosis of existing breast cancer instead of causing new breast cancers. The findings of this meta-analysis along with a plausible biologic mechanism (estrogen stimulates breast cancer cells) suggest a causal relationship between OC use and breast cancer. They also indicate that the risk is small, decreases with time, and is lower among low-dose OC users. It is reassuring that the breast cancers found among OC users is less clinically advanced than those found in never-users.

  10. Preventing Breast Cancer: Making Progress

    MedlinePlus

    ... 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 ...

  11. Understanding your breast cancer risk

    MedlinePlus

    ... ency/patientinstructions/000830.htm Understanding your breast cancer risk To use the sharing features on this page, ... you can do to help prevent breast cancer. Risk Factors You Cannot Control Risk factors you cannot ...

  12. Angiogenesis: prognostic significance in laryngeal cancer.

    PubMed

    Beatrice, F; Cammarota, R; Giordano, C; Corrado, S; Ragona, R; Sartoris, A; Bussolino, F; Valente, G

    1998-01-01

    The aim of this study was to evaluate the role of angiogenesis in the progression of laryngeal squamous cell carcinoma (LSCC). We correlated disease-free survival with microvessel count (MC) in the hot spot areas of 97 randomly selected caucasian males with LSCC followed for 60 to 90 months after surgery with or without radiotherapy. The results obtained indicate that: a) MC higher than 130 microvessels/mm2 is a cut-off value that distinguished patients who relapsed during the follow up period; b) multivariated analysis indicates that MC (p < 0.00001) is an independent predictor of disease free-survival; c) multivariated analysis selectively done on cases with relapse demonstrates that MC correlates with the presence of metastasis (or/and M) with local relapse (T). We suggest that MC is useful in the assessment of prognosis in LSCC and probably will permit selection of patients that could benefit from anti-angiogenic therapy associated with chemotherapy and/or radiotherapy.

  13. Computerized Cognitive Retraining in Improving Cognitive Function in Breast Cancer Survivors

    ClinicalTrials.gov

    2017-03-02

    Cancer Survivor; 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

  14. Cardiac Rehabilitation Program in Improving Cardiorespiratory Fitness in Stage 0-III Breast Cancer Survivors

    ClinicalTrials.gov

    2017-08-17

    Cancer Survivor; 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

  15. Obesity and cancer phenotype: Is angiogenesis a missed link?

    PubMed

    Mendonça, Fernando; Soares, Raquel

    2015-10-15

    Obesity remains nowadays one of the main threats to human health, being a problem of worldwide proportions. It is characterized by augmented storage of fatty acids in an enlarged adipose tissue. This process is possible thanks to a rich capillary network, supported by a mechanism that has also a crucial role on cancer: angiogenesis. Given that several studies point obesity as a risk factor for cancer development, angiogenesis may be approached as the missed link between these two pathologies. Understanding the different pathways behind angiogenesis becomes essential to break this link by developing new anti-angiogenic therapies or improving the actual ones. In the first phase, this paper will focus the structural and cellular changes that adipose tissue suffers in obesity. Then, the main pro-angiogenic players will be reviewed, taking into account the pathways that explain their putative role in obesity-cancer link. Finally, the clinical implications of the presented mechanisms will also be regarded, being the main focus on the anti-angiogenic therapies. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Omega-3 Fatty Acid in Treating Patients With Stage I-III Breast Cancer

    ClinicalTrials.gov

    2017-03-13

    Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Male 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

  17. Hormones and Breast Cancer.

    DTIC Science & Technology

    1997-10-01

    OHE 1 hypothesis are cancer patients and lacto- vegetarians . The evidence is rather clear that certain sparse. Schneider and co-workers used a Both of... Cancer PRINCIPAL INVESTIGATOR: Giske Ursin, M.D., Ph.D. CONTRACTING ORGANIZATION: University of Southern California School of Medicine Los Angeles...TYPE AND DATES COVERED I October 1997 Final (30 Sep 94 - 29 Sep 97) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Hormones and Breast Cancer DAMD17-94-J

  18. Vasopressin and Breast Cancer

    DTIC Science & Technology

    1996-09-01

    receptors7:on-breast cancer cells represents a way in which these peptides might influence cancer cell pathophysiology. However, the expression of...National Institutes of Health . In the conduct of research utilIzing recombinant DNA, the nvestigator(s) adhered to the NIH G.idelines for Research...possible autocrine/paracrine role for this peptide in cancer cells. In support of this hypothesis vasopressin was shown to have a growth-promoting influence

  19. Pregnancy associated breast cancer and pregnancy after breast cancer treatment.

    PubMed

    Doğer, Emek; Calışkan, Eray; Mallmann, Peter

    2011-01-01

    Breast cancer is one of the most common cancers diagnosed during pregnancy and its frequency is increasing as more women postpone their pregnancies to their thirties and forties. Breast cancer diagnosis during pregnancy and lactation is difficult and complex both for the patient and doctors. Delay in diagnosis is frequent and treatment modalities are difficult to accept for the pregnant women. The common treatment approach is surgery after diagnosis, chemotherapy after the first trimester and radiotherapy after delivery. Even though early stage breast cancers have similar prognosis, advanced stage breast cancers diagnosed during pregnancy and lactation have poorer prognosis than similar stage breast cancers diagnosed in non-pregnant women. Women who desire to become pregnant after treatment of breast cancer will have many conflicts. Although the most common concern is recurrence of breast cancer due to pregnancy, the studies conducted showed that pregnancy has no negative effect on breast cancer prognosis. In this review we search for the frequency of breast cancer during pregnancy, the histopathological findings, risk factor, diagnostic and treatment modalities. We reviewed the literature for evidence based findings to help consult the patients on the outcome of breast cancer diagnosed during pregnancy and lactation, and also inform the patients who desire to become pregnant after breast cancer according to current evidences.

  20. Pregnancy associated breast cancer and pregnancy after breast cancer treatment

    PubMed Central

    Doğer, Emek; Çalışkan, Eray; Mallmann, Peter

    2011-01-01

    Breast cancer is one of the most common cancers diagnosed during pregnancy and its frequency is increasing as more women postpone their pregnancies to their thirties and forties. Breast cancer diagnosis during pregnancy and lactation is difficult and complex both for the patient and doctors. Delay in diagnosis is frequent and treatment modalities are difficult to accept for the pregnant women. The common treatment approach is surgery after diagnosis, chemotherapy after the first trimester and radiotherapy after delivery. Even though early stage breast cancers have similar prognosis, advanced stage breast cancers diagnosed during pregnancy and lactation have poorer prognosis than similar stage breast cancers diagnosed in non-pregnant women. Women who desire to become pregnant after treatment of breast cancer will have many conflicts. Although the most common concern is recurrence of breast cancer due to pregnancy, the studies conducted showed that pregnancy has no negative effect on breast cancer prognosis. In this review we search for the frequency of breast cancer during pregnancy, the histopathological findings, risk factor, diagnostic and treatment modalities. We reviewed the literature for evidence based findings to help consult the patients on the outcome of breast cancer diagnosed during pregnancy and lactation, and also inform the patients who desire to become pregnant after breast cancer according to current evidences. PMID:24592003

  1. Affluence and Breast Cancer.

    PubMed

    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 < 0.001). There was a significant relationship between node involvement and income in Whites in 198 USA counties. Income was significantly correlated with 5-year relative survival in Whites with localized breast cancer. Income was not correlated with 5-year survival of Black race (p = 0.364) or other races (p = 0

  2. The effect of cancer procoagulant on expression of metastatic and angiogenic markers in breast cancer and embryonic stem cell lines.

    PubMed

    Kee, Nalise Low Ah; Naudé, Ryno J; Blatch, Gregory L; Frost, Carminita L

    2012-03-01

    Cancer procoagulant is present only in malignant tumours and the undifferentiated tissues of human placenta. Its possible role in angiogenesis and metastasis was investigated. Cancer procoagulant increased the steady-state mRNA level of L1 cell adhesion molecule (L1CAM) in MCF-7 breast cancer cells and E14 mouse embryonic stem cells (MESCs), while an increase in angiogenin mRNA was observed in MDA-MB-231 breast cancer cells. Furthermore, production of vascular endothelial growth factor (VEGF) protein in MCF-7 breast cancer cells and E14 MESCs, but decreased in MDA-MB-231 breast cancer cells. We conclude that cancer procoagulant could potentially play a part in angiogenesis in cancer and vascular development during embryonic development.

  3. Angiogenesis and VEGF expression in pre-invasive lesions of the human breast.

    PubMed

    Viacava, Paolo; Naccarato, Antonio Giuseppe; Bocci, Guido; Fanelli, Giovanni; Aretini, Paolo; Lonobile, Antonino; Evangelista, Giuseppe; Montruccoli, Giancarlo; Bevilacqua, Generoso

    2004-10-01

    Angiogenesis (as microvascular density-MVD) and vascular endothelial growth factor (VEGF) expression were evaluated by immunohistochemistry in all types of human pre-invasive breast lesion, un-associated with invasive carcinoma, including florid ductal hyperplasia of usual type (FDHUT, 40 cases), atypical ductal hyperplasia (ADH, 10), well-differentiated intraductal carcinoma (WDIC, 16), intermediately differentiated intraductal carcinoma (IDIC, 25), poorly differentiated intraductal carcinoma (PDIC, 20), atypical lobular hyperplasia (ALH, 13), and lobular carcinoma in situ (LCIS, 12). Both parameters were also studied in normal glandular structures obtained from normal breasts or from breasts containing pre-invasive lesions. Increased vascularization was present in all lesion types (MVD mean values (expressed as vessel number/mm(2)): 115 +/- 8 in normal lobules, 146 +/- 26 in lesions; p < 0.05) and increased with lesion severity. In ductal lesions, MVDs were significantly higher in PDIC (190 +/- 65) and IDIC (167 +/- 61) than in FDHUT (123 +/- 40) and ADH (122 +/- 47); MVD was much higher in PDIC than in WDIC (p < 0.001). WDIC showed peculiar features, with a degree of vascularization closer to hyperplasia than to the other histological types of in situ ductal cancer; this observation is in line with the hypothesis that IDIC and PDIC may originate 'de novo', without a mandatory transition through WDIC. LCIS was more vascularized than ALH (168 +/- 50 and 125 +/- 40, respectively; p < 0.05), showing MVD values similar to those of PDIC and IDIC. The vascularization of normal lobules was constant, regardless of their association with lesions. VEGF expression in normal glandular structures was lower than in lesions, with the highest levels found in ductal lesions when compared with lobular lesions. No correlation was found between VEGF expression and the degree and/or type of vascularization.

  4. Role of Caveolin-1 in Prostate Cancer Angiogenesis

    DTIC Science & Technology

    2009-12-01

    1996;86:353–64. 26. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases . Nature 2000;407:249–57. 27. Frank PG, Woodman SE, Park DS, Lisanti...several multidrug-resistant and metastatic cancer cell lines. In many of these studies, cav-1 was shown to correlate with aggressive disease ( reviewed ...Prostatic Diseases (2009), 1–6 & 2009 Nature Publishing Group All rights reserved 1365-7852/09 $32.00 www.nature.com/pcan Cav-1 upregulation in prostate

  5. Diet and breast cancer.

    PubMed

    Bradlow, H Leon; Sepkovic, Daniel W

    2002-06-01

    The preponderance of evidence suggests a role for fat and alcohol as risk factors for breast cancer. The role of milk is more controversial with some studies suggesting that milk is a risk factor and others that consumption of milk is protective against breast cancer. No other major nutrient appears to play a significant role in increasing breast cancer risk. On the other hand, there is increasing evidence that a variety of micronutrients and hormones appear to have significant anticancer activity. These range from steroids such as dehydroepiandrosterone (DHEA) and its analysis to indoles, isothiocyanates, and isoflavone derivatives. These compounds act directly by interfering with cyclins and promoting apoptosis as well as indirectly by altering estrogen metabolism in a favorable direction. These effects are not merely theoretical actions in cell culture and tissue explants; they have been demonstrated in human patients as a range of studies have demonstrated.

  6. Targeting HER 2 and angiogenesis in gastric cancer.

    PubMed

    Jomrich, G; Schoppmann, S F

    2016-01-01

    Gastric cancer is one of the most commonly diagnosed and the second leading cause of cancer death worldwide. Surgery combined with multimodal therapy remains the only curative therapy. However, local relapse or distant metastases occur in more than 50% of radically resected patients. Due to molecular therapies, targeting HER2 and angiogenesis, major advances in the treatment of gastric cancer could be achieved. Nevertheless, development of resistance to monoclonal antibodies, such as trastuzumab, is arising. Currently a number of promising new therapeutic are under investigation, combining chemotherapy with newly developed agents to overcome cancer resistance. In this review we report current clinical applications of targeted therapies and overview ongoing trials, investigating the use of monoclonal antibodies in (HER2 positive) gastric cancer.

  7. Virtual Weight Loss Program in Maintaining Weight in African American Breast Cancer Survivors

    ClinicalTrials.gov

    2017-01-19

    Cancer Survivor; Invasive Breast Carcinoma; 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

  8. Targeting angiogenesis for the treatment of prostate cancer

    PubMed Central

    Antonarakis, Emmanuel S; Carducci, Michael A

    2014-01-01

    Introduction While multiple therapies exist that prolong the lives of men with advanced prostate cancer, none are curative. This had led to a search to uncover novel targets for prostate cancer therapy, distinct from those of traditional hormonal approaches, chemotherapies, immunotherapies and bone-targeting approaches. The process of tumor angiogenesis is one target that is being exploited for therapeutic gain. Areas covered The most promising anti-angiogenic approaches for treatment of prostate cancer, focusing on clinical development of selected agents. These include VEGF-directed therapies, tyrosine kinase inhibitors, tumor-vascular disrupting agents, immunomodulatory drugs and miscellaneous anti-angiogenic agents. While none of these drugs have yet entered the market for the treatment of prostate cancer, several are now being tested in Phase III registrational trials. Expert opinion The development of anti-angiogenic agents for prostate cancer has met with several challenges. This includes discordance between traditional prostate-specific antigen responses and clinical responses, which have clouded clinical trial design and interpretation, potential inadequate exposure to anti-angiogenic therapies with premature discontinuation of study drugs and the development of resistance to anti-angiogenic monotherapies. These barriers will hopefully be overcome with the advent of more potent agents, the use of dual angiogenesis inhibition and the design of more informative clinical trials. PMID:22413953

  9. Marine-Derived Angiogenesis Inhibitors for Cancer Therapy

    PubMed Central

    Wang, Ying-Qing; Miao, Ze-Hong

    2013-01-01

    Angiogenesis inhibitors have been successfully used for cancer therapy in the clinic. Many marine-derived natural products and their analogues have been reported to show antiangiogenic activities. Compared with the drugs in the clinic, these agents display interesting characteristics, including diverse sources, unique chemical structures, special modes of action, and distinct activity and toxicity profiles. This review will first provide an overview of the current marine-derived angiogenesis inhibitors based on their primary targets and/or mechanisms of action. Then, the marine-derived antiangiogenic protein kinase inhibitors will be focused on. And finally, the clinical trials of the marine-derived antiangiogenic agents will be discussed, with special emphasis on their application potentials, problems and possible coping strategies in their future development as anticancer drugs. PMID:23502698

  10. COX-2 and Prostate Cancer Angiogenesis

    DTIC Science & Technology

    2002-03-01

    sphingomyelin to ceramide , a mediator of apopto- sis (Figure 1).10 The initial interest in COX-2 grew out of the In colon cancer, much of the focus has been...Sphingomyelin - Ceramide Arachidanic Acid \\\\ COX-1 / COX-2 Prostaglandin G2 Prostaglandin H2 Oxidation of Xenobiolics Prostaglandins Malordialdehyde FIGURE 1...variety of tissues in- corneal model, it was demonstrated that endothe- cluding skin , urinary bladder, gastric mucosa, lial cell COX-2 is essential for

  11. Inflammatory Breast Cancer from Metastatic Ovarian Cancer

    PubMed Central

    Achariyapota, Vuthinun; Chuangsuwanich, Tuenjai

    2016-01-01

    Metastases to the breast from tumors other than breast carcinomas are extremely rare and represent only 0.2–1.3% of all diagnosed malignant breast tumors. Furthermore, while the most common sites for advanced ovarian cancer metastases are the liver, lung, and pleura, metastasis to the breast from a primary ovarian cancer is uncommon and has only been reported in 0.03–0.6% of all breast cancers. Here we describe a case report of a 50-year-old female patient with a rare case of breast metastases from an advanced ovarian cancer, presenting as inflammatory breast cancer. Our observations emphasize the clinical importance of distinguishing between primary and metastatic breast cancer during diagnosis for the purpose of appropriate prognosis and treatment. PMID:27047697

  12. Accelerated Radiation Therapy After Surgery in Treating Patients With Breast Cancer

    ClinicalTrials.gov

    2017-09-21

    Inflammatory Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Tubular Ductal Breast Carcinoma

  13. Early detection of breast cancer.

    PubMed

    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.

  14. Expression of Matrix Metalloproteinases in Human Breast Cancer Tissues

    PubMed Central

    Benson, Chellakkan Selvanesan; Babu, Somasundaram Dinesh; Radhakrishna, Selvi; Selvamurugan, Nagarajan; Sankar, Bhaskaran Ravi

    2013-01-01

    BACKGROUND: Breast cancer is the most common cancer affecting women in the world today. Matrix metalloproteinases (MMPs) are a family of endopeptidases that can degrade extracellular matrix proteins and promote cell invasion and metastasis. MMPs are differentially expressed and their expressions are often associated with a poor prognosis for patients. OBJECTIVE: The aim of this study is to investigate and compare the expression of MMPs in different grades of human breast cancer tissues with normal breast tissues. PATIENTS AND METHODS: We collected 39 breast cancer samples (24 grade II and 15 grade III) along with 16 normal breast tissues from outside the tumor margin during cancer removal surgery. The samples were analysed for the expression of all known MMPs using real-time quantitative PCR. RESULTS: The results indicate that mRNA expressions of MMP-1, -9,-11,-15,-24 and -25 were upregulated in breast cancer tissues when compared to normal breast tissues. But, the mRNA expressions of MMP-10 and MMP-19 were downregulated in cancer tissue. In membrane associated MMPs like MMP-15 and MMP-24 we found a grade dependent increase of their mRNA expression. CONCLUSION: Our studies demonstrate that MMPs are differentially regulated in breast cancer tissues and they might play various roles in tumor invasion, metastasis and angiogenesis. Thus, MMPs are of immense value to be studied as diagnostic markers and drug target. PMID:23568046

  15. Breast cancer epidemiology.

    PubMed

    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

  16. Pertuzumab, Trastuzumab, and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With HER2-Positive Advanced Breast Cancer

    ClinicalTrials.gov

    2016-12-23

    HER2-positive Breast Cancer; Recurrent Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Breast Adenocarcinoma; Inflammatory Breast Carcinoma

  17. Breast cancer screening with digital breast tomosynthesis.

    PubMed

    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. Broad targeting of angiogenesis for cancer prevention and therapy.

    PubMed

    Wang, Zongwei; Dabrosin, Charlotta; Yin, Xin; Fuster, Mark M; Arreola, Alexandra; Rathmell, W Kimryn; Generali, Daniele; Nagaraju, Ganji P; El-Rayes, Bassel; Ribatti, Domenico; Chen, Yi Charlie; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G; Nowsheen, Somaira; Amedei, Amedeo; Niccolai, Elena; Amin, Amr; Ashraf, S Salman; Helferich, Bill; Yang, Xujuan; Guha, Gunjan; Bhakta, Dipita; Ciriolo, Maria Rosa; Aquilano, Katia; Chen, Sophie; Halicka, Dorota; Mohammed, Sulma I; Azmi, Asfar S; Bilsland, Alan; Keith, W Nicol; Jensen, Lasse D

    2015-12-01

    Deregulation of angiogenesis--the growth of new blood vessels from an existing vasculature--is a main driving force in many severe human diseases including cancer. As such, tumor angiogenesis is important for delivering oxygen and nutrients to growing tumors, and therefore considered an essential pathologic feature of cancer, while also playing a key role in enabling other aspects of tumor pathology such as metabolic deregulation and tumor dissemination/metastasis. Recently, inhibition of tumor angiogenesis has become a clinical anti-cancer strategy in line with chemotherapy, radiotherapy and surgery, which underscore the critical importance of the angiogenic switch during early tumor development. Unfortunately the clinically approved anti-angiogenic drugs in use today are only effective in a subset of the patients, and many who initially respond develop resistance over time. Also, some of the anti-angiogenic drugs are toxic and it would be of great importance to identify alternative compounds, which could overcome these drawbacks and limitations of the currently available therapy. Finding "the most important target" may, however, prove a very challenging approach as the tumor environment is highly diverse, consisting of many different cell types, all of which may contribute to tumor angiogenesis. Furthermore, the tumor cells themselves are genetically unstable, leading to a progressive increase in the number of different angiogenic factors produced as the cancer progresses to advanced stages. As an alternative approach to targeted therapy, options to broadly interfere with angiogenic signals by a mixture of non-toxic natural compound with pleiotropic actions were viewed by this team as an opportunity to develop a complementary anti-angiogenesis treatment option. As a part of the "Halifax Project" within the "Getting to know cancer" framework, we have here, based on a thorough review of the literature, identified 10 important aspects of tumor angiogenesis and the

  19. Contrast Enhanced Maximum Intensity Projection Ultrasound Imaging for Assessing Angiogenesis in Murine Glioma and Breast Tumor Models: A Comparative Study

    PubMed Central

    Forsberg, Flemming; Ro, Raymond J.; Fox, Traci B; Liu, Ji-Bin; Chiou, See-Ying; Potoczek, Magdalena; Goldberg, Barry B

    2010-01-01

    The purpose of this study was to prospectively compare noninvasive, quantitative measures of vascularity obtained from 4 contrast enhanced ultrasound (US) techniques to 4 invasive immunohistochemical markers of tumor angiogenesis in a large group of murine xenografts. Glioma (C6) or breast cancer (NMU) cells were implanted in 144 rats. The contrast agent Optison (GE Healthcare, Princeton, NJ) was injected in a tail vein (dose: 0.4ml/kg). Power Doppler imaging (PDI), pulse-subtraction harmonic imaging (PSHI), flash-echo imaging (FEI), and Microflow imaging (MFI; a technique creating maximum intensity projection images over time) was performed with an Aplio scanner (Toshiba America Medical Systems, Tustin, CA) and a 7.5 MHz linear array. Fractional tumor neovascularity was calculated from digital clips of contrast US, while the relative area stained was calculated from specimens. Results were compared using a factorial, repeated measures ANOVA, linear regression and z-tests. The tortuous morphology of tumor neovessels was visualized better with MFI than with the other US modes. Cell line, implantation method and contrast US imaging technique were significant parameters in the ANOVA model (p<0.05). The strongest correlation determined by linear regression in the C6 model was between PSHI and percent area stained with CD31 (r=0.37, p<0.0001). In the NMU model the strongest correlation was between FEI and COX-2 (r=0.46, p<0.0001). There were no statistically significant differences between correlations obtained with the various US methods (p>0.05). In conclusion, the largest study of contrast US of murine xenografts to date has been conducted and quantitative contrast enhanced US measures of tumor neovascularity in glioma and breast cancer xenograft models appear to provide a noninvasive marker for angiogenesis; although the best method for monitoring angiogenesis was not conclusively established. PMID:21144542

  20. Surveying Breast Cancer's Genomic Landscape.

    PubMed

    2016-07-01

    An in-depth analysis has produced the most comprehensive portrait to date of the myriad genomic alterations involved in breast cancer. In sequencing the whole genomes of 560 breast cancers and combining this information with published data from another 772 breast tumors, the research team uncovered several new genes and mutational signatures that potentially influence this disease.

  1. Ultrasound in Detecting Taxane-Induced Neuropathy in Patients With Breast Cancer

    ClinicalTrials.gov

    2017-05-15

    Peripheral Neuropathy; Stage 0 Breast Cancer; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  2. Breast cancer in systemic lupus.

    PubMed

    Bernatsky, S; Ramsey-Goldman, R; Petri, M; Urowitz, M B; Gladman, D D; Fortin, P F; Ginzler, E; Romero-Diaz, J; Peschken, C; Jacobsen, S; Hanly, J G; Gordon, C; Nived, O; Yelin, E H; Isenberg, D; Rahman, A; Bae, S-C; Joseph, L; Witte, T; Ruiz-Irastorza, G; Aranow, C; Kamen, D; Sturfeldt, G; Foulkes, W D; Hansen, J E; St Pierre, Y; Raymer, P Chrétien; Tessier-Cloutier, B; Clarke, A E

    2017-03-01

    Objective There is a decreased breast cancer risk in systemic lupus erythematosus (SLE) versus the general population. We assessed a large sample of SLE patients, evaluating demographic and clinical characteristics and breast cancer risk. Methods We performed case-cohort analyses within a multi-center international SLE sample. We calculated the breast cancer hazard ratio (HR) in female SLE patients, relative to demographics, reproductive history, family history of breast cancer, and time-dependent measures of anti-dsDNA positivity, cumulative disease activity, and drugs, adjusted for SLE duration. Results There were 86 SLE breast cancers and 4498 female SLE cancer-free controls. Patients were followed on average for 7.6 years. Versus controls, SLE breast cancer cases tended to be white and older. Breast cancer cases were similar to controls regarding anti-dsDNA positivity, disease activity, and most drug exposures over time. In univariate and multivariate models, the principal factor associated with breast cancers was older age at cohort entry. Conclusions There was little evidence that breast cancer risk in this SLE sample was strongly driven by any of the clinical factors that we studied. Further search for factors that determine the lower risk of breast cancer in SLE may be warranted.

  3. Breast cancer screening and biomarkers.

    PubMed

    Brooks, Mai

    2009-01-01

    Annual screening mammograms have been shown to be cost-effective and are credited for the decline in mortality of breast cancer. New technologies including breast magnetic resonance imaging (MRI) may further improve early breast cancer detection in asymptomatic women. Serum tumor markers such as CA 15-3, carcinoembyonic antigen (CEA), and CA 27-29 are ordered in the clinic mainly for disease surveillance, and not useful for detection of localized cancer. This review will discuss blood-based markers and breast-based markers, such as nipple/ductal fluid, with an emphasis on biomarkers for early detection of breast cancer. In the future, it is likely that a combination approach to simultaneously measure multiple markers would be most successful in detecting early breast cancer. Ideally, such a biomarker panel should be able to detect breast cancer in asymptomatic patients, even in the setting of normal mammogram and physical examination results.

  4. Broad targeting of angiogenesis for cancer prevention and therapy

    PubMed Central

    Wang, Zongwei; Dabrosin, Charlotta; Yin, Xin; Fuster, Mark M.; Arreola, Alexandra; Rathmell, W. Kimryn; Generali, Daniele; Nagaraju, Ganji P.; El-Rayes, Bassel; Ribatti, Domenico; Chen, Yi Charlie; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G.; Nowsheen, Somaira; Amedei, Amedeo; Niccolai, Elena; Amin, Amr; Ashraf, S. Salman; Helferich, Bill; Yang, Xujuan; Guha, Gunjan; Bhakta, Dipita; Ciriolo, Maria Rosa; Aquilano, Katia; Chen, Sophie; Halicka, Dorota; Mohammed, Sulma I.; Azmi, Asfar S.; Bilsland, Alan; Keith, W. Nicol; Jensen, Lasse D.

    2015-01-01

    Deregulation of angiogenesis – the growth of new blood vessels from an existing vasculature – is a main driving force in many severe human diseases including cancer. As such, tumor angiogenesis is important for delivering oxygen and nutrients to growing tumors, and therefore considered an essential pathologic feature of cancer, while also playing a key role in enabling other aspects of tumor pathology such as metabolic deregulation and tumor dissemination/metastasis. Recently, inhibition of tumor angiogenesis has become a clinical anti-cancer strategy in line with chemotherapy, radiotherapy and surgery, which underscore the critical importance of the angiogenic switch during early tumor development. Unfortunately the clinically approved anti-angiogenic drugs in use today are only effective in a subset of the patients, and many who initially respond develop resistance over time. Also, some of the anti-angiogenic drugs are toxic and it would be of great importance to identify alternative compounds, which could overcome these drawbacks and limitations of the currently available therapy. Finding “the most important target” may, however, prove a very challenging approach as the tumor environment is highly diverse, consisting of many different cell types, all of which may contribute to tumor angiogenesis. Furthermore, the tumor cells themselves are genetically unstable, leading to a progressive increase in the number of different angiogenic factors produced as the cancer progresses to advanced stages. As an alternative approach to targeted therapy, options to broadly interfere with angiogenic signals by a mixture of non-toxic natural compound with pleiotropic actions were viewed by this team as an opportunity to develop a complementary anti-angiogenesis treatment option. As a part of the “Halifax Project” within the “Getting to know cancer” framework, we have here, based on a thorough review of the literature, identified 10 important aspects of tumor

  5. Inhibitory effect of ibuprofen on tumor survival and angiogenesis in gastric cancer cell.

    PubMed

    Akrami, Hassan; Aminzadeh, Saman; Fallahi, Hossein

    2015-05-01

    Numerous epidemiological studies have suggested effectiveness of long-term and regular use of non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and aspirin, in preventing and treatment of certain cancers including prostate, colon, breast, lung, and gastric cancers. We have studied the potential anti-turmeric effect of ibuprofen in adenocarcinoma gastric cell line (AGS). The effects of ibuprofen were investigated on cell proliferation, apoptosis, angiogenesis, and expression of stemness marker genes using real-time RT-PCR, DNA laddering, and tube formation assays via ECM gel and human umbilical vein endothelial cells (HUVECs). Annexin-V-FLUOS and propidium iodide (PI) were used to stain the apoptotic cells. Our findings indicate that ibuprofen at the concentrations of 100, 200, 300, 400, and 500 μM is able to reduce the cancerous characteristics of the AGS cells by inducing apoptosis, inhibition of cell proliferation, and angiogenesis. Real-time RT-PCR showed that ibuprofen altered the expression of several genes including Akt, P53, PCNA, Bax, and Bcl2 in the AGS cells. In addition, reduction in CD44 and OCT3/4 transcript levels revealed that ibuprofen reduces the stemness of the AGS cells and therefore it could be used as a potential anti-tumor drug.

  6. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Dr. Harry Mahtani analyzes the gas content of nutrient media from Bioreactor used in research on human breast cancer. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues.

  7. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Dr. Harry Mahtani analyzes the gas content of nutrient media from Bioreactor used in research on human breast cancer. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues.

  8. Genetic epidemiology of breast cancer.

    PubMed

    Thompson, W D

    1994-07-01

    It has been recognized for some time that a family history of breast cancer is associated rather strongly with a woman's own risk of developing the disease. Recent segregation analyses of population-based data on familial patterns provide evidence for a rare autosomal dominant allele that increases a carrier's susceptibility to breast cancer. The estimated proportion of breast cancer patients who carry this allele declines sharply with age at diagnosis. Empirical estimates of the risk associated with particular patterns of family history of breast cancer indicate the following: (1) having any first-degree relative with breast cancer increases a woman's risk of breast cancer 1.5-3-fold, depending on age, (2) having multiple first degree relatives affected is associated with particularly elevated risks, (3) having a second-degree relative affected increases the risk by approximately 50%, (4) affected family members on the maternal side and the paternal side contribute similarly to the risk, (5) a family history of breast cancer is associated with bilateral disease, and (6) breast cancer in males is associated with breast cancer in female relatives in much the same way as is breast cancer in women. Ovarian cancer clearly has been shown to be associated with breast cancer in families, and genetic linkage has provided strong evidence for a breast-ovarian cancer gene located somewhere on chromosome 17q. At the population level, having a first degree relative with ovarian cancer may be at least as predictive of a woman's risk for developing breast cancer as is having a second-degree relative with breast cancer. Considerably weaker evidence points to a possible familial relationship between breast and endometrial cancer and between breast cancer in women and prostatic cancer in males. The clinical applications of the genetic epidemiology of breast cancer are complicated by uncertainty as to the efficacy of mammographic screening in women under the age of 50. For the vast

  9. Azacitidine in Treating Patients With Triple Negative Stage I-IV Invasive Breast Cancer That Can Be Removed By Surgery

    ClinicalTrials.gov

    2014-02-05

    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; Triple-negative Breast Cancer

  10. Mindfulness Meditation or Survivorship Education in Improving Behavioral Symptoms in Younger Stage 0-III Breast Cancer Survivors (Pathways to Wellness)

    ClinicalTrials.gov

    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

  11. Heterogeneity in breast cancer.

    PubMed

    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.

  12. Hormones, Women and Breast Cancer

    MedlinePlus

    ... diagnosed? The most common way to find breast cancer is through a breast exam or mammogram (x-ray). Some women at high risk may need a screening MRI (magnetic resonance imaging) scan, which is more sensitive than a mammogram. ...

  13. Role of metabolic modulator Bet-CA in altering mitochondrial hyperpolarization to suppress cancer associated angiogenesis and metastasis

    PubMed Central

    Saha, Suchandrima; Ghosh, Monisankar; Dutta, Samir Kumar

    2016-01-01

    Solid tumors characteristically reflect a metabolic switching from glucose oxidation to glycolysis that plays a fundamental role in angiogenesis and metastasis to facilitate aggressive tumor outcomes. Hyperpolarized mitochondrial membrane potential is a manifestation of malignant cells that compromise the intrinsic pathways of apoptosis and confer a suitable niche to promote the cancer associated hallmark traits. We have previously reported that co-drug Bet-CA selectively targets cancer cells by inducing metabolic catastrophe without a manifest in toxicity. Here we report that the same molecule at a relatively lower concentration deregulates the cardinal phenotypes associated with angiogenesis and metastasis. In mice syngeneic 4T1 breast cancer model, Bet-CA exhibited effective abrogation of angiogenesis and concomitantly obliterated lung metastasis consistent with altered mitochondrial bioenergetics. Furthermore, Bet-CA significantly lowered vascular endothelial growth factor (VEGF) levels and obviated matrix metalloproteases (MMP-2/9) production directly to the criterion where abrogation of autocrine VEGF/VEGFR2 signalling loop was documented. In vitro studies anticipatedly documented the role of Bet-CA in inhibiting actin remodeling, lamellipodia formation and cell membrane ruffling to constitutively suppress cell motility and invasion. Results comprehensively postulate that Bet-CA, a mitochondria targeting metabolic modulator may serve as an excellent candidate for combating angiogenesis and metastasis. PMID:27003027

  14. Male breast cancer.

    PubMed

    Reis, Leonardo Oliveira; Dias, Fernando Gf; Castro, Marcos As; Ferreira, Ubirajara

    2011-06-01

    Male breast cancer (MBC) is a rare disease. However, as global populace ages, there is a trend to MBC increasing. Although aetiology is still unclear, constitutional, environmental, hormonal (abnormalities in estrogen/androgen balance) and genetic (positive family history, Klinefelter syndrome, mutations in BRCA1 and specially BRCA2) risk factors are already known. Clinic manifestation is painless hard and fixed nodule in the subareolar region in 75% of cases, with nipple commitment earlier than in women. Breast cancer has similar prognostic factors in males and females, among which axillary adenopathy (present in 40-55% cases) is the most important one. Although mammography, ultrasonography and scintigraphy can be useful tools in diagnosis; clinical assessment, along with a confirmatory biopsy, remains the main step in the evaluation of men with breast lesions. Infiltrating ductal carcinoma is the most frequent histological type. The established standard of care is modified radical mastectomy followed by tamoxifen for endocrine-responsive positive disease, although other options are being explored. While similarities between breast cancer in males and females exist, it is not appropriate to extrapolate data from female disease to the treatment of male. There is a need for specific multi-institutional trials to better understanding of clinicopathologic features and establishment of optimal therapy for this disease.

  15. Pharmacokinetically Guided Everolimus in Patients With Breast Cancer, Pancreatic Neuroendocrine Tumors, or Kidney Cancer

    ClinicalTrials.gov

    2016-12-09

    Estrogen Receptor-positive Breast Cancer; Gastrinoma; Glucagonoma; HER2-negative Breast Cancer; Insulinoma; Mucositis; Oral Complications; Pancreatic Polypeptide Tumor; Progesterone Receptor-positive Breast Cancer; Recurrent Breast Cancer; Recurrent Islet Cell Carcinoma; Recurrent Renal Cell Cancer; Somatostatinoma; Stage III Renal Cell Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Renal Cell Cancer

  16. [Occult multicentric breast cancer].

    PubMed

    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.

  17. What Happens After Treatment for Breast Cancer in Men?

    MedlinePlus

    ... Men After Treatment What Happens After Treatment for Breast Cancer in Men? For many men with breast cancer, ... Breast Cancer in Men Stops Working More In Breast Cancer In Men About Breast Cancer in Men Causes, ...

  18. Increasing Breast Cancer Surveillance among African American Breast Cancer Survivors

    DTIC Science & Technology

    2007-07-01

    predictors of surveillance and follow-up care is Baldwin’s Afrocentric model for describing AA women’s participation in breast and cervical cancer screening...African American women’s participation in breast and cervical cancer early detection and screening. Adv Nurs Sci. 1996;19(2):27Y42. 28. Marin G. Subjective...AD_________________ Award Number: DAMD17-03-1-0454 TITLE: Increasing Breast Cancer Surveillance

  19. Angiogenesis inhibitors for the treatment of ovarian cancer

    PubMed Central

    Gaitskell, Kezia; Martinek, Igor; Bryant, Andrew; Kehoe, Sean; Nicum, Shibani; Morrison, Jo

    2014-01-01

    Background Many women with ovarian cancer eventually develop resistance to conventional chemotherapy drugs, and so novel agents are being developed to target specific molecular pathways. One such class of drugs inhibits angiogenesis (the development of new blood vessels), which is essential for tumour growth. It is important to establish whether the addition of these new drugs to conventional chemotherapy regimens improves survival, and what the side-effects may be. Objectives To compare the effectiveness and toxicities of angiogenesis inhibitors in the treatment of ovarian cancer. Search methods We sought to identify completed randomised controlled trials (RCTs) by searching The Cochrane Gynaecological Cancer Review Group’s Trial Register, The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 10), MEDLINE and EMBASE (1990 to October 2010). We also searched registers of clinical trials, and contacted investigators of completed and ongoing trials for further information. Selection criteria Randomised controlled studies comparing angiogenesis inhibitors with either standard chemotherapy or no treatment, in women with ovarian cancer. Data collection and analysis Two independent authors carried out data collection and extraction. We used a random-effects model for pooling data. Main results We did not find any fully-published, completed RCTs of angiogenesis inhibitors that met our inclusion criteria. We identified five abstracts of completed RCTs of four different angiogenesis-inhibiting agents, with a total of 3701 participants. Meta-analysis of two trials found no statistically significant difference in overall survival (OS) between women with newly-diagnosed advanced ovarian cancer who received concurrent and maintenance bevacizumab compared to those who received chemotherapy (carboplatin and paclitaxel) alone. However, women who received concurrent and maintenance bevacizumab had their risk of disease progression reduced

  20. Educating Normal Breast Mucosa to Prevent Breast Cancer

    DTIC Science & Technology

    2015-05-01

    1 Award Number: W81XWH-12-1-0059 TITLE: Educating normal breast mucosa to prevent breast cancer PRINCIPAL INVESTIGATOR: Keith L Knutson...SUBTITLE Educating Normal Breast Mucosa to Prevent Breast Cancer 5a. CONTRACT NUMBER W81XWH-12-1-0059 5b. GRANT NUMBER W81XWH-12-1-0059 5c...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Breast cancer develops from breast mucosa and breast mucosa has intact immune system to

  1. Breast-Conserving Surgery Followed by Radiation Therapy With MRI-Detected Stage I or Stage II Breast Cancer

    ClinicalTrials.gov

    2011-12-07

    Ductal Breast Carcinoma in Situ; Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Male Breast Cancer; Medullary Ductal Breast Carcinoma With Lymphocytic Infiltrate; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Tubular Ductal Breast Carcinoma

  2. Molecular Imaging of Breast Cancer: Role of RGD Peptides.

    PubMed

    Chakravarty, Rubel; Chakraborty, Sudipta; Dash, Ashutosh

    2015-01-01

    Breast cancer is the leading cause of cancer deaths among women of all ages worldwide. With advances in molecular imaging procedures, it has been possible to detect breast cancer in its early stage, determine the extent of the disease to administer appropriate therapeutic protocol and also monitor the effects of treatment. By accurately characterizing the tumor properties and biological processes involved, molecular imaging can play a crucial role in minimizing the morbidity and mortality associated with breast cancer. The integrin αvβ3 plays an important role in breast cancer angiogenesis and is expressed on tumor endothelial cells as well as on some tumor cells. It is a receptor for the extracellular matrix proteins with the exposed arginine-glycine-aspartic acid (RGD) tripeptide sequence and therefore RGD peptides can preferentially bind to integrin αvβ3. In this context, targeting tumor vasculature or tumor cells by RGD-based probes is a promising strategy for molecular imaging of breast cancer. Using RGD-based probes, several preclinical studies have employed different imaging modalities such as positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), ultrasound and optical imaging for visualization of integrin αvβ3 expression in breast cancer models. Limited clinical trials using (18)F-labeled RGD peptides have also been initiated for non-invasive detection and staging of breast cancer. Herein, we provide a comprehensive overview of the latest advances in molecular imaging of breast cancer using RGD peptide-based probes and discuss the challenges and opportunities for advancement of the field. The reported strategies for molecular imaging of breast cancer using RGD peptide-based probes holds promise for making clinically translatable advances that can positively impact the overall diagnostic and therapeutic processes and result in improved quality of life for breast cancer patients.

  3. You, Your Teenage Daughter and Breast Cancer.

    ERIC Educational Resources Information Center

    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)

  4. How Is Breast Cancer in Men Diagnosed?

    MedlinePlus

    ... Men Early Detection, Diagnosis, and Staging How Is Breast Cancer in Men Diagnosed? Medical history and physical exam ... in Men Survival Rates, by Stage More In Breast Cancer In Men About Breast Cancer in Men Causes, ...

  5. You, Your Teenage Daughter and Breast Cancer.

    ERIC Educational Resources Information Center

    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)

  6. Axillary Lymph Nodes and Breast Cancer

    MedlinePlus

    ... nodes . The axillary nodes are the first place breast cancer is likely to spread. During breast surgery, some ... if cancer cells are present. This helps determine breast cancer stage and guide treatment. So, it is more ...

  7. Breast cancer fear in African American breast cancer survivors.

    PubMed

    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.

  8. Role of Chemokines in Non-Small Cell Lung Cancer: Angiogenesis and Inflammation

    PubMed Central

    Rivas-Fuentes, Selma; Salgado-Aguayo, Alfonso; Pertuz Belloso, Silvana; Gorocica Rosete, Patricia; Alvarado-Vásquez, Noé; Aquino-Jarquin, Guillermo

    2015-01-01

    Non-small cell lung cancer (NSCLC) is one of the most common types of aggressive cancer. The tumor tissue, which shows an active angiogenesis, is composed of neoplastic and stromal cells, and an abundant inflammatory infiltrate. Angiogenesis is important to support tumor growth, while infiltrating cells contribute to the tumor microenvironment through the secretion of growth factors, cytokines and chemokines, important molecules in the progression of the disease. Chemokines are important in development, activation of the immune response, and physiological angiogenesis. Chemokines have emerged as important regulators in the pathophysiology of cancer. These molecules are involved in the angiogenesis/angiostasis balance and in the recruitment of tumor infiltrating hematopoietic cells. In addition, chemokines promote tumor cell survival, as well as the directing and establishment of tumor cells to metastasis sites. The findings summarized here emphasize the central role of chemokines as modulators of tumor angiogenesis and their potential role as therapeutic targets in the inflammatory process of NSCLC angiogenesis. PMID:26316890

  9. Reproduction and Breast Cancer Risk

    PubMed Central

    Hanf, Volker; Hanf, Dorothea

    2014-01-01

    Summary Reproduction is doubtlessly one of the main biological meanings of life. It is therefore not surprising that various aspects of reproduction impact on breast cancer risk. Various developmental levels may become targets of breast tumorigenesis. This review follows the chronologic sequence of events in the life of a female at risk, starting with the intrauterine development. Furthermore, the influence of both contraceptive measures and fertility treatment on breast cancer development is dealt with, as well as various pregnancy-associated factors, events, and perinatal outcomes. Finally, the contribution of breast feeding to a reduced breast cancer risk is discussed. PMID:25759622

  10. Breast Cancer Metastasis

    PubMed Central

    Marino, Natascia; Woditschka, Stephan; Reed, L. Tiffany; Nakayama, Joji; Mayer, Musa; Wetzel, Maria; Steeg, Patricia S.

    2014-01-01

    Despite important progress in adjuvant and neoadjuvant therapies, metastatic disease often develops in breast cancer patients and remains the leading cause of their deaths. For patients with established metastatic disease, therapy is palliative, with few breaks and with mounting adverse effects. Many have hypothesized that a personalized or precision approach (the terms are used interchangeably) to cancer therapy, in which treatment is based on the individual characteristics of each patient, will provide better outcomes. Here, we discuss the molecular basis of breast cancer metastasis and the challenges in personalization of treatment. The instability of metastatic tumors remains a leading obstacle to personalization, because information from a patient’s primary tumor may not accurately reflect the metastasis, and one metastasis may vary from another. Furthermore, the variable presence of tumor subpopulations, such as stem cells and dormant cells, may increase the complexity of the targeted treatments needed. Although molecular signatures and circulating biomarkers have been identified in breast cancer, there is lack of validated predictive molecular markers to optimize treatment choices for either prevention or treatment of metastatic disease. Finally, to maximize the information that can be obtained, increased attention to clinical trial design in the metastasis preventive setting is needed. PMID:23895915

  11. [Immediate breast reconstruction for breast cancer].

    PubMed

    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.

  12. Role of TGF-β in breast cancer bone metastases

    PubMed Central

    Chiechi, Antonella; Waning, David L.; Stayrook, Keith R.; Buijs, Jeroen T.; Guise, Theresa A.; Mohammad, Khalid S.

    2014-01-01

    Breast cancer is the most prevalent cancer among females worldwide leading to approximately 350,000 deaths each year. It has long been known that cancers preferentially metastasize to particular organs, and bone metastases occur in ~70% of patients with advanced breast cancer. Breast cancer bone metastases are predominantly osteolytic and accompanied by increased fracture risk, pain, nerve compression and hypercalcemia, causing severe morbidity. In the bone matrix, transforming growth factor-β (TGF-β) is one of the most abundant growth factors, which is released in active form upon tumor-induced osteoclastic bone resorption. TGF-β, in turn, stimulates bone metastatic tumor cells to secrete factors that further drive osteolytic bone destruction adjacent to the tumor. Thus, TGF-β is a crucial factor responsible for driving the feed-forward vicious cycle of cancer growth in bone. Moreover, TGF-β activates epithelial-to-mesenchymal transition, increases tumor cell invasiveness and angiogenesis and induces immunosuppression. Blocking the TGF-β signaling pathway to interrupt this vicious cycle between breast cancer and bone offers a promising target for therapeutic intervention to decrease skeletal metastasis. This review will describe the role of TGF-β in breast cancer and bone metastasis, and pre-clinical and clinical data will be evaluated for the potential use of TGF-β inhibitors in clinical practice to treat breast cancer bone metastases. PMID:24558636

  13. Cancer-associated fibroblasts promote angiogenesis in gastric cancer through galectin-1 expression.

    PubMed

    Tang, Dong; Gao, Jun; Wang, Sen; Ye, Nianyuan; Chong, Yang; Huang, Yuqin; Wang, Jie; Li, Bin; Yin, Wei; Wang, Daorong

    2016-02-01

    Galectin-1, an evolutionarily conserved glycan-binding protein with angiogenic potential, was recently identified as being overexpressed in cancer-associated fibroblasts (CAFs) of gastric cancer. The role of endogenous CAF-derived galectin-1 on angiogenesis in gastric cancer and the mechanism involved remain unknown. Immunohistochemical staining was used to investigate the correlation between galectin-1 and vascular endothelial growth factor (VEGF) and CD31 expression in gastric cancer tissues and normal gastric tissues. Galectin-1 was knocked down in CAFs isolated from gastric cancer using small interfering ribonucleic acid (RNA), or overexpressed using recombinant lentiviruses, and the CAFs were co-cultured with human umbilical vein endothelial cells (HUVECs) or cancer cells. Subsequently, proliferation, migration, tube formation, and VEGF/VEGF receptor (VEGFR) 2 expression were detected. The role of CAF-derived galectin-1 in tumor angiogenesis in vivo was studied using the chick chorioallantoic membrane (CAM) assay. Galectin-1 was highly expressed in the CAFs and was positively associated with VEGF and CD31 expression. In the co-culture, high expression of galectin-1 in the CAFs increased HUVEC proliferation, migration, tube formation, and VEGFR2 phosphorylation and enhanced VEGF expression in gastric cancer cells. The CAM assay indicated that high expression of galectin-1 in the CAFs accelerated tumor growth and promoted angiogenesis. In contrast, galectin-1 knockdown in the CAFs significantly inhibited this effect. CAF-derived galectin-1 significantly promotes angiogenesis in gastric cancer and may be a target for angiostatic therapy.

  14. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Dr. Robert Richmond extracts breast cell tissue from one of two liquid nitrogen dewars. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues.

  15. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Breast tissue specimens in traditional sample dishes. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues.

  16. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Breast tissue specimens in traditional sample dishes. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues.

  17. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Dr. Robert Richmond extracts breast cell tissue from one of two liquid nitrogen dewars. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues.

  18. Angiogenesis inhibitors in the treatment of lung cancer.

    PubMed

    Shepherd, F A

    2001-12-01

    Numerous inhibitors of angiogenesis are currently under study in lung cancer. Four trials of adjuvant interferon after chemotherapy for small cell lung cancer (SCLC) were negative. Several metalloproteinase inhibitors (MMPIs) are now in study in SCLC and non-small cell lung cancer (NSCLC). Two large randomized trials have closed recently in which Marimastat 10 mg bid was compared to placebo in responding patients with SCLC. Two randomized studies of Prinomastat versus placebo with combination chemotherapy in advanced NSCLC have also completed accrual. The results of these trials are not yet available, but should be reported in mid-2001. A Phase III trial of BMS-275291, a broad-spectrum MMPI in combination with paclitaxel and carboplatin is open for patients with advanced NSCLC. Neovastat, a standardized shark cartilage extract is under study in inoperable Stage III NSCLC. VEG-F gene expression is increased in many tumors including NSCLC, and may act as a paracrine mediator of growth. A randomized Phase II trial of paclitaxel and carboplatin with or without a recombinant humanized anti-VEG-F has been undertaken in NSCLC. Modestly better response and survival were seen with anti-VEG-F and a large Phase III trial is planned. Numerous receptor tyrosine kinases (TK) have been found to be directly or indirectly involved in angiogenesis including Flk-1, Flt-l, Tie-1 and Tie-2. SU5416 is a small molecular TK inhibitor and potent inhibitor of VEG-F-mediated Flk-1 receptor signaling. Another TK inhibitor SU6668 blocks VEG-F, bFGF and PDGF receptor signaling. It is orally available, and it may be evaluated in lung cancer trials in the near future. ZD4190 is an inhibitor of KDR/Flk-1 that may be evaluated in SCLC. Thalidomide has recently been shown in pre-clinical models to be anti-angiogenic. A randomized trial of paclitaxel/carboplatin and radiation with or without thalidomide is open for patients with Stage IIIB NSCLC in the United States. Numerous other anti-angiogenesis

  19. Present and future evolution of advanced breast cancer therapy

    PubMed Central

    2010-01-01

    Although the introduction of novel therapies and drug combinations has improved the prognosis of metastatic breast cancer, the disease remains incurable. Increased knowledge of the biology and the molecular alterations in breast cancer has facilitated the design of targeted therapies. These agents include receptor and nonreceptor tyrosine kinase inhibitors (epidermal growth factor receptor family), intracellular signaling pathways (phosphatidylinositol-3-kinase, AKT, mammalian target of rapamycin) angiogenesis inhibitors and agents that interfere with DNA repair (poly(ADP-ribose) polymerase inhibitors). In the present review, we present the most promising studies of these new targeted therapies and novel combinations of targeted therapies with cytotoxic agents. PMID:21050422

  20. MET deregulation in breast cancer

    PubMed Central

    Landi, Lorenza

    2015-01-01

    Background Mesenchymal-epithelial transition (MET) is an oncogene encoding for a trans-membrane tyrosine kinase receptor activated by the hepatocyte growth factor (HGF). MET has a normal function in organ development during embryogenesis and in tissue homeostasis during adult life. Deregulation of HGF/MET signaling pathway is frequently observed in many cancer types, conferring invasive growth and tendency to progression. MET deregulation is due to gene amplification or increased copy number, gene mutation, receptor over-expression or ligand autocrine loops activation. These events lead to migration, invasion, proliferation, metastatic spread and neo-angiogenesis of cancer cells, suggesting that anti-HGF/MET agents may represent a potential antitumor strategy. In breast cancer (BC), preclinical and clinical data demonstrated the role of HGF/MET signalling pathway in carcinogenesis, disease progression and resistance features. Methods For this review article, all published data on HGF/MET in BC were collected and analyzed. Results Several evidences underline that, in early BC, MET over-expression has an independent negative prognostic significance, regardless of method used for evaluation and BC subtypes. Available data suggest that MET is a relevant target particularly in basal-like (BL) and in triple negative BC. Moreover, preclinical and retrospective data support the critical role of MET deregulation in the development of resistance to target-agents, such as anti-HER2 strategies. Conclusions MET is a promising new target in BC. Several anti-MET agents are under investigation and ongoing clinical trials will clarify its relevance in BC treatment. PMID:26366398

  1. Ginseng Metabolites on Cancer Chemoprevention: An Angiogenesis Link?

    PubMed

    Wang, Chong-Zhi; Cai, Yi; Anderson, Samantha; Yuan, Chun-Su

    2015-09-01

    Cancer is a leading cause of death in the United States. Angiogenesis inhibitors have been introduced for the treatment of cancer. Based on the fact that many anticancer agents have been developed from botanical sources, there is a significant untapped resource to be found in natural products. American ginseng is a commonly used herbal medicine in the U.S., which possess antioxidant properties. After oral ingestion, natural ginseng saponins are biotransformed to their metabolites by the enteric microbiome before being absorbed. The major metabolites, ginsenoside Rg3 and compound K, showed significant potent anticancer activity compared to that of their parent ginsenosides Rb1, Rc and Rd. In this review, the molecular mechanisms of ginseng metabolites on cancer chemoprevention, especially apoptosis and angiogenic inhibition, are discussed. Ginseng gut microbiome metabolites showed significant anti-angiogenic effects on pulmonary, gastric and ovarian cancers. This review suggests that in addition to the chemopreventive effects of ginseng compounds, as angiogenic inhibitors, ginsenoside metabolites could be used in combination with other cancer chemotherapeutic agents in cancer management.

  2. Ginseng Metabolites on Cancer Chemoprevention: An Angiogenesis Link?

    PubMed Central

    Wang, Chong-Zhi; Cai, Yi; Anderson, Samantha; Yuan, Chun-Su

    2015-01-01

    Cancer is a leading cause of death in the United States. Angiogenesis inhibitors have been introduced for the treatment of cancer. Based on the fact that many anticancer agents have been developed from botanical sources, there is a significant untapped resource to be found in natural products. American ginseng is a commonly used herbal medicine in the U.S., which possess antioxidant properties. After oral ingestion, natural ginseng saponins are biotransformed to their metabolites by the enteric microbiome before being absorbed. The major metabolites, ginsenoside Rg3 and compound K, showed significant potent anticancer activity compared to that of their parent ginsenosides Rb1, Rc and Rd. In this review, the molecular mechanisms of ginseng metabolites on cancer chemoprevention, especially apoptosis and angiogenic inhibition, are discussed. Ginseng gut microbiome metabolites showed significant anti-angiogenic effects on pulmonary, gastric and ovarian cancers. This review suggests that in addition to the chemopreventive effects of ginseng compounds, as angiogenic inhibitors, ginsenoside metabolites could be used in combination with other cancer chemotherapeutic agents in cancer management. PMID:26941993

  3. Closantel Suppresses Angiogenesis and Cancer Growth in Zebrafish Models.

    PubMed

    Zhu, Xiao-Yu; Xia, Bo; Liu, Hong-Cui; Xu, Yi-Qiao; Huang, Chang-Jiang; Gao, Ji-Min; Dong, Qiao-Xiang; Li, Chun-Qi

    2016-04-05

    Angiogenesis has emerged as an important therapeutic target in several major diseases, including cancer and age-related macular degeneration. The zebrafish offer the potential for high-throughput drug discovery in a whole vertebrate system. In this study, we have taken advantage of the transgenic Tg (fli1a:EGFP) zebrafish line to screen the U.S. Drug Collection Library and identified 11 old drugs with antiangiogenic activity, including Closantel, an FDA-approved broad-spectrum salicylanilide antiparasitic drug for a variety of types of animals. Closantel was confirmed to have antiangiogenic activity in zebrafish with a half-inhibitory concentration (IC50) at 1.69 μM on the intersegmental vessels and 1.45 μM on the subintestinal vessels. Closantel also markedly suppressed cancer growth in zebrafish xenotransplanted with human lymphoma, cervical cancer, pancreatic cancer, and liver cancer cells, generally in a dose-dependent manner. These data reveal that Closantel has antiangiogenesis and anticancer effects and could be a potential drug candidate for animal and human cancer treatments. Further study is needed to clarify the mechanisms involved in the antiangiogenesis and anticancer effects of Closantel.

  4. [Organized breast cancer screening].

    PubMed

    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

  5. Tumor Angiogenesis as a Target for Dietary Cancer Prevention

    PubMed Central

    Li, William W.; Li, Vincent W.; Hutnik, Michelle; Chiou, Albert S.

    2012-01-01

    Between 2000 and 2050, the number of new cancer patients diagnosed annually is expected to double, with an accompanying increase in treatment costs of more than $80 billion over just the next decade. Efficacious strategies for cancer prevention will therefore be vital for improving patients' quality of life and reducing healthcare costs. Judah Folkman first proposed antiangiogenesis as a strategy for preventing dormant microtumors from progressing to invasive cancer. Although antiangiogenic drugs are now available for many advanced malignancies (colorectal, lung, breast, kidney, liver, brain, thyroid, neuroendocrine, multiple myeloma, myelodysplastic syndrome), cost and toxicity considerations preclude their broad use for cancer prevention. Potent antiangiogenic molecules have now been identified in dietary sources, suggesting that a rationally designed antiangiogenic diet could provide a safe, widely available, and novel strategy for preventing cancer. This paper presents the scientific, epidemiologic, and clinical evidence supporting the role of an antiangiogenic diet for cancer prevention. PMID:21977033

  6. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    High magnification view of human primary breast tumor cells after 56 days of culture in a NASA Bioreactor. The arrow points to bead surface indicating breast cancer cells (as noted by the staining of tumor cell intermediate filaments). NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Jearne Becker, University of South Florida

  7. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    High magnification view of human primary breast tumor cells after 56 days of culture in a NASA Bioreactor. The arrow points to bead surface indicating breast cancer cells (as noted by the staining of tumor cell intermediate filaments). NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Jearne Becker, University of South Florida

  8. Genistein Programming Against Breast Cancer

    DTIC Science & Technology

    2003-09-01

    DEOXYRIBONUCLEIC ACIDS, *GENES, *DIET, *ESTROGENS, *SOY PROTEIN, *BREAST CANCER, RATS , CHEMICALS, MOLECULES, ENZYMES, PROTEINS, SENSITIVITY, WOMEN, SENSE ORGANS, ASIA, MAMMARY GLANDS, METHYLATION, ANDROGENS, TRANSFERASES.

  9. Unemployment among breast cancer survivors.

    PubMed

    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.

  10. Amphiphysin and Breast Cancer

    DTIC Science & Technology

    1998-10-01

    condition appears to represent a novel entity within the emerging family of neurological autoimmune paraneoplastic syndromes , conditions in which...We have recently identified a new human syndrome characterized by breast cancer, autoimmunity directed against the neuronal protein in amphiphysin...and Stiff-Man syndrome (SMS). SMS is a rare disease of the central nervous system characterized by progressive rigidity of the body musculature. This

  11. Erythropoietin and Breast Cancer

    DTIC Science & Technology

    2008-03-01

    and/or findings contained in this report are those of the author( s ) and should not be construed as an official Department of the Army position...CONTRACT NUMBER Erythropoietin and Breast Cancer 5b. GRANT NUMBER W81XWH-06-1-0737 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) 5d. PROJECT...NUMBER Arthur J. Sytkowski, MD 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) 8. PERFORMING

  12. Breast cancer risk factors

    PubMed Central

    Ciszewski, Tomasz; Łopacka-Szatan, Karolina; Miotła, Paweł; Starosławska, Elżbieta

    2015-01-01

    Breast cancer is the most frequently diagnosed neoplastic disease in women around menopause often leading to a significant reduction of these women's ability to function normally in everyday life. The increased breast cancer incidence observed in epidemiological studies in a group of women actively participating in social and professional life implicates the necessity of conducting multidirectional studies in order to identify risk factors associated with the occurrence of this type of neoplasm. Taking the possibility of influencing the neoplastic transformation process in individuals as a criterion, all the risk factors initiating the process can be divided into two groups. The first group would include inherent factors such as age, sex, race, genetic makeup promoting familial occurrence of the neoplastic disease or the occurrence of benign proliferative lesions of the mammary gland. They all constitute independent parameters and do not undergo simple modification in the course of an individual's life. The second group would include extrinsic factors conditioned by lifestyle, diet or long-term medical intervention such as using oral hormonal contraceptives or hormonal replacement therapy and their influence on the neoplastic process may be modified to a certain degree. Identification of modifiable factors may contribute to development of prevention strategies decreasing breast cancer incidence. PMID:26528110

  13. Effect of Nitroxoline on Angiogenesis and Growth of Human Bladder Cancer

    PubMed Central

    Shim, Joong Sup; Matsui, Yoshiyuki; Bhat, Shridhar; Nacev, Benjamin A.; Xu, Jing; Bhang, Hyo-eun C.; Dhara, Surajit; Han, Kee Chung; Chong, Curtis R.; Pomper, Martin G.; So, Alan

    2010-01-01

    Background Angiogenesis plays an important role in tumor growth and metastasis; therefore, inhibition of angiogenesis is a promising strategy for developing new anticancer drugs. Type 2 methionine aminopeptidase (MetAP2) protein is likely a molecular target of angiogenesis inhibitors. Methods Nitroxoline, an antibiotic used to treat urinary tract infections, was identified from a high-throughput screen of a library of 175 000 compounds for MetAP2 inhibitors and from a parallel screen using the Johns Hopkins Drug Library to identify currently used clinical drugs that can also inhibit human umbilical vein endothelial cells (HUVEC) proliferation. To investigate the mechanism of action of nitroxoline, inhibition of MetAP2 activity and induction of senescence were assessed in HUVEC. To test the antiangiogenic activity of nitroxoline, endothelial tube formation in Matrigel and microvessel formation in Matrigel plugs in vivo were assessed. Antitumor efficacy of nitroxoline was evaluated in mouse models of human breast cancer xenograft (n = 10) and bladder cancer orthotopic xenograft (n = 11). Furthermore, the mechanism of action of nitroxoline was investigated in vivo. Results Nitroxoline inhibited MetAP2 activity in vitro (half maximal inhibitory concentration [IC50] = 54.8 nM, 95% confidence interval [CI] = 22.6 to 132.8 nM) and HUVEC proliferation (IC50 = 1.9 μM, 95% CI = 1.54 to 2.39 μM). Nitroxoline inhibited MetAP2 activity in HUVEC in a dose-dependent manner and induced premature senescence in a biphasic manner. Nitroxoline inhibited endothelial tube formation in Matrigel and reduced microvessel density in vivo. Mice (five per group) treated with nitroxoline showed a 60% reduction in tumor volume in breast cancer xenografts (tumor volume on day 30, vehicle vs nitroxoline, mean = 215.4 vs 86.5 mm3, difference = 128.9 mm3, 95% CI = 32.9 to 225.0 mm3, P = .012) and statistically significantly inhibited growth of bladder cancer in an orthotopic mouse model (tumor

  14. Breast-feeding after breast cancer in childbearing women.

    PubMed

    Camune, Barbara; Gabzdyl, Elizabeth

    2007-01-01

    According to the American Cancer Society in 2007, about 178,000 women are diagnosed with breast cancer each year in the United States. Of these, 25% have tumors in their childbearing years and may desire future opportunities for pregnancy and lactation. Although there is a multitude of options related to preserving fertility, little is known about the residual effects of breast cancer treatment and the ability to breast-feed afterward. This article describes the epidemiological relationship between breast cancer and pregnancy and lactation. Basic types of treatment for breast cancer including surgery, chemotherapy, and radiation are reviewed. Practical information on how to support breast-feeding after breast cancer is included.

  15. Simvastatin inhibits tumor angiogenesis in HER2-overexpressing human colorectal cancer.

    PubMed

    Li, Gang; Zheng, Junhua; Xu, Bin; Ling, Jie; Qiu, Wei; Wang, Yongbing

    2017-01-01

    Overexpression of the HER2 oncogene contributes to tumor angiogenesis, which is an essential hallmark of cancer. Simvastatin has been reported to exhibit antitumor activities in several cancers; however, its roles and molecular mechanismsin the regulation of colorectal angiogenesis remain to be clarified. Here, we show that colon cancer cells express high levels of VEGF, total HER2 and phosphorylated HER2, and simvastatin apparently decreased their expression in HER2-overexpressing colon cancer cells. Simvastatin pretreatment reduced endothelial tube formation in vitro and microvessel density in vivo. Furthermore, simvastatin markedly inhibited tumor angiogenesis even in the presence of heregulin (HRG)-β1 (a HER2 co-activator) pretreatment in HER2+ tumor cells. Mechanistic investigation showed that simvastatin significantly abrogated HER2-induced tumor angiogenesis by inhibiting VEGF secretion. Together, these results provide a novel mechanism underlying the simvastatin-induced inhibition of tumor angiogenesis through regulating HER2/VEGF axis.

  16. Ginseng on Cancer: Potential Role in Modulating Inflammation-Mediated Angiogenesis.

    PubMed

    Dai, Daisy; Zhang, Chun-Feng; Williams, Stephanie; Yuan, Chun-Su; Wang, Chong-Zhi

    2017-01-01

    Angiogenesis is a regulated process integral to many physiological and pathological situations, including carcinogenesis and tumor growth. The majority of the angiogenic processes are related to inflammation. The interplay is not only important in the case of pathogen entry but also influential in chronic inflammatory diseases, tumor growth and tissue regeneration. Modulating the interaction between inflammation and angiogenesis could be an important target for cancer treatment and wound healing alike. Ginseng has a wide range of pharmacological effects, including anti-inflammatory and angiogenesis-modulating activities. This paper presents the recent research progresses on the inhibition of angiogenesis by ginseng and its active constituents, with a particular focus on processes mediated by inflammation. The modulatory role of ginseng compounds in inflammation-mediated angiogenesis involving hypoxia and microRNAs are also discussed. With the potential to modulate the angiogenesis at the transcriptional, translational and protein signaling level via various different mechanisms, ginseng could prove to be effective in cancer therapeutics.

  17. Rosuvastatin in Treating Women With Cardiovascular Complications Who Are Undergoing Chemotherapy For Breast Cancer

    ClinicalTrials.gov

    2017-05-25

    Cardiovascular Complications; Recurrent Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  18. Vascular and Cognitive Assessments in Patients With Breast Cancer Undergoing Chemotherapy After Surgery

    ClinicalTrials.gov

    2017-02-20

    Cognitive/Functional Effects; 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

  19. Pathways to Breast Cancer Recurrence

    PubMed Central

    2013-01-01

    Breast cancer remains a deadly disease, even with all the recent technological advancements. Early intervention has made an impact, but an overwhelmingly large number of breast cancer patients still live under the fear of “recurrent” disease. Breast cancer recurrence is clinically a huge problem and one that is largely not well understood. Over the years, a number of factors have been studied with an overarching aim of being able to prognose recurrent disease. This paper attempts to provide an overview of our current knowledge of breast cancer recurrence and its associated challenges. Through a survey of the literature on cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), various signaling pathways such as Notch/Wnt/hedgehog, and microRNAs (miRNAs), we also examine the hypotheses that are currently under investigation for the prevention of breast cancer recurrence. PMID:23533807

  20. Breast cancer statistics and markers.

    PubMed

    Donepudi, Mallika Siva; Kondapalli, Kasturi; Amos, Seelam Jeevan; Venkanteshan, Pavithra

    2014-01-01

    Breast cancer is one of the familiar diseases in women. Incidence and mortality due to cancer, particularly breast cancer has been increasing for last 50 years, even though there is a lacuna in the diagnosis of breast cancer at early stages. According to World Health Organization (WHO) 2012 reports, breast cancer is the leading cause of death in women, accounting 23% of all cancer deaths. In Asia, one in every three women faces the risk of breast cancer in their lifetime as per reports of WHO 2012. Here, the review is been focused on different breast cancer markers, that is, tissue markers (hormone receptors, human epidermal growth factor-2, urokinase plasminogen activator, plasminogen activator inhibitor, p53 and cathepsin D), genetic markers (BRAC1 and 2 and gene expression microarray technique, etc.), and serum markers (CA 15.3, BR 27.29, MCA, CA 549, carcinoembryonic antigen, oncoproteins, and cytokeratins) used in present diagnosis, but none of the mentioned markers can diagnose breast cancer at an early stage. There is a disquieting need for the identification of best diagnosing marker, which can be able to diagnose even in early stage of breast carcinogenesis.

  1. Gene expression profiling of breast cancer in Lebanese women

    PubMed Central

    Makoukji, Joelle; Makhoul, Nadine J.; Khalil, Maya; El-Sitt, Sally; Aldin, Ehab Saad; Jabbour, Mark; Boulos, Fouad; Gadaleta, Emanuela; Sangaralingam, Ajanthah; Chelala, Claude; Boustany, Rose-Mary; Tfayli, Arafat

    2016-01-01

    Breast cancer is commonest cancer in women worldwide. Elucidation of underlying biology and molecular pathways is necessary for improving therapeutic options and clinical outcomes. Molecular alterations in breast cancer are complex and involve cross-talk between multiple signaling pathways. The aim of this study is to extract a unique mRNA fingerprint of breast cancer in Lebanese women using microarray technologies. Gene-expression profiles of 94 fresh breast tissue samples (84 cancerous/10 non-tumor adjacent samples) were analyzed using GeneChip Human Genome U133 Plus 2.0 arrays. Quantitative real-time PCR was employed to validate candidate genes. Differentially expressed genes between breast cancer and non-tumor tissues were screened. Significant differences in gene expression were established for COL11A1/COL10A1/MMP1/COL6A6/DLK1/S100P/CXCL11/SOX11/LEP/ADIPOQ/OXTR/FOSL1/ACSBG1 and C21orf37. Pathways/diseases representing these genes were retrieved and linked using PANTHER®/Pathway Studio®. Many of the deregulated genes are associated with extracellular matrix, inflammation, angiogenesis, metastasis, differentiation, cell proliferation and tumorigenesis. Characteristics of breast cancers in Lebanese were compared to those of women from Western populations to explain why breast cancer is more aggressive and presents a decade earlier in Lebanese victims. Delineating molecular mechanisms of breast cancer in Lebanese women led to key genes which could serve as potential biomarkers and/or novel drug targets for breast cancer. PMID:27857161

  2. Gene expression profiling of breast cancer in Lebanese women.

    PubMed

    Makoukji, Joelle; Makhoul, Nadine J; Khalil, Maya; El-Sitt, Sally; Aldin, Ehab Saad; Jabbour, Mark; Boulos, Fouad; Gadaleta, Emanuela; Sangaralingam, Ajanthah; Chelala, Claude; Boustany, Rose-Mary; Tfayli, Arafat

    2016-11-18

    Breast cancer is commonest cancer in women worldwide. Elucidation of underlying biology and molecular pathways is necessary for improving therapeutic options and clinical outcomes. Molecular alterations in breast cancer are complex and involve cross-talk between multiple signaling pathways. The aim of this study is to extract a unique mRNA fingerprint of breast cancer in Lebanese women using microarray technologies. Gene-expression profiles of 94 fresh breast tissue samples (84 cancerous/10 non-tumor adjacent samples) were analyzed using GeneChip Human Genome U133 Plus 2.0 arrays. Quantitative real-time PCR was employed to validate candidate genes. Differentially expressed genes between breast cancer and non-tumor tissues were screened. Significant differences in gene expression were established for COL11A1/COL10A1/MMP1/COL6A6/DLK1/S100P/CXCL11/SOX11/LEP/ADIPOQ/OXTR/FOSL1/ACSBG1 and C21orf37. Pathways/diseases representing these genes were retrieved and linked using PANTHER(®)/Pathway Studio(®). Many of the deregulated genes are associated with extracellular matrix, inflammation, angiogenesis, metastasis, differentiation, cell proliferation and tumorigenesis. Characteristics of breast cancers in Lebanese were compared to those of women from Western populations to explain why breast cancer is more aggressive and presents a decade earlier in Lebanese victims. Delineating molecular mechanisms of breast cancer in Lebanese women led to key genes which could serve as potential biomarkers and/or novel drug targets for breast cancer.

  3. Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Older Patients With Locally Advanced or Metastatic Breast Cancer

    ClinicalTrials.gov

    2016-10-14

    Male Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer

  4. Therapeutic targets of triple-negative breast cancer: a review

    PubMed Central

    Jamdade, Vinayak S; Sethi, Nikunj; Mundhe, Nitin A; Kumar, Parveen; Lahkar, Mangala; Sinha, Neeraj

    2015-01-01

    Breast cancer (BC) is the second most common cause of cancer deaths. Triple-negative breast cancer (TNBC) does not show immunohistochemical expression of oestrogen receptors, progesterone receptors or HER2. At present, no suitable treatment option is available for patients with TNBC. This dearth of effective conventional therapies for the treatment of advanced stage breast cancer has provoked the development of novel strategies for the management of patients with TNBC. This review presents recent information associated with different therapeutic options for the treatment of TNBC focusing on promising targets such as the Notch signalling, Wnt/β-catenin and Hedgehog pathways, in addition to EGFR, PARP1, mTOR, TGF-β and angiogenesis inhibitors. PMID:26040571

  5. The Role of Cytokines in Breast Cancer Development and Progression

    PubMed Central

    Esquivel-Velázquez, Marcela; Ostoa-Saloma, Pedro; Palacios-Arreola, Margarita Isabel; Nava-Castro, Karen E.; Castro, Julieta Ivonne

    2015-01-01

    Cytokines are highly inducible, secretory proteins that mediate intercellular communication in the immune system. They are grouped into several protein families that are referred to as tumor necrosis factors, interleukins, interferons, and colony-stimulating factors. In recent years, it has become clear that some of these proteins as well as their receptors are produced in the organisms under physiological and pathological conditions. The exact initiation process of breast cancer is unknown, although several hypotheses have emerged. Inflammation has been proposed as an important player in tumor initiation, promotion, angiogenesis, and metastasis, all phenomena in which cytokines are prominent players. The data here suggest that cytokines play an important role in the regulation of both induction and protection in breast cancer. This knowledge could be fundamental for the proposal of new therapeutic approaches to particularly breast cancer and other cancer-related disorders. PMID:25068787

  6. The role of cytokines in breast cancer development and progression.

    PubMed

    Esquivel-Velázquez, Marcela; Ostoa-Saloma, Pedro; Palacios-Arreola, Margarita Isabel; Nava-Castro, Karen E; Castro, Julieta Ivonne; Morales-Montor, Jorge

    2015-01-01

    Cytokines are highly inducible, secretory proteins that mediate intercellular communication in the immune system. They are grouped into several protein families that are referred to as tumor necrosis factors, interleukins, interferons, and colony-stimulating factors. In recent years, it has become clear that some of these proteins as well as their receptors are produced in the organisms under physiological and pathological conditions. The exact initiation process of breast cancer is unknown, although several hypotheses have emerged. Inflammation has been proposed as an important player in tumor initiation, promotion, angiogenesis, and metastasis, all phenomena in which cytokines are prominent players. The data here suggest that cytokines play an important role in the regulation of both induction and protection in breast cancer. This knowledge could be fundamental for the proposal of new therapeutic approaches to particularly breast cancer and other cancer-related disorders.

  7. Drugs Approved for Breast Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for breast cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  8. Hormone Therapy for Breast Cancer

    MedlinePlus

    ... outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P–2 trial. JAMA 2006; 295(23):2727– ... and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: Preventing breast cancer. Cancer Prevention ...

  9. PEG-3, a nontransforming cancer progression gene, is a positive regulator of cancer aggressiveness and angiogenesis.

    PubMed

    Su, Z Z; Goldstein, N I; Jiang, H; Wang, M N; Duigou, G J; Young, C S; Fisher, P B

    1999-12-21

    Cancer is a progressive disease culminating in acquisition of metastatic potential by a subset of evolving tumor cells. Generation of an adequate blood supply in tumors by production of new blood vessels, angiogenesis, is a defining element in this process. Although extensively investigated, the precise molecular events underlying tumor development, cancer progression, and angiogenesis remain unclear. Subtraction hybridization identified a genetic element, progression elevated gene-3 (PEG-3), whose expression directly correlates with cancer progression and acquisition of oncogenic potential by transformed rodent cells. We presently demonstrate that forced expression of PEG-3 in tumorigenic rodent cells, and in human cancer cells, increases their oncogenic potential in nude mice as reflected by a shorter tumor latency time and the production of larger tumors with increased vascularization. Moreover, inhibiting endogenous PEG-3 expression in progressed rodent cancer cells by stable expression of an antisense expression vector extinguishes the progressed cancer phenotype. Cancer aggressiveness of PEG-3 expressing rodent cells correlates directly with increased RNA transcription, elevated mRNA levels, and augmented secretion of vascular endothelial growth factor (VEGF). Furthermore, transient ectopic expression of PEG-3 transcriptionally activates VEGF in transformed rodent and human cancer cells. Taken together these data demonstrate that PEG-3 is a positive regulator of cancer aggressiveness, a process regulated by augmented VEGF production. These studies also support an association between expression of a single nontransforming cancer progression-inducing gene, PEG-3, and the processes of cancer aggressiveness and angiogenesis. In these contexts, PEG-3 may represent an important target molecule for developing cancer therapeutics and inhibitors of angiogenesis.

  10. Breast Cancer Stem Cells

    PubMed Central

    Velasco-Velázquez, Marco A.; Homsi, Nora; De La Fuente, Marisol; Pestell, Richard G.

    2012-01-01

    Breast cancer stem cells (BCSCs) constitute a subpopulation of tumor cells that express stem cell-associated markers and have a high capacity for tumor generation in vivo. Identification of BCSCs from tumor samples or breast cancer cell lines has been based mainly on CD44+/CD24−/low or ALDH+ phenotypes. BCSCs isolation has allowed the analysis of the molecular mechanisms involved in their origin, self-renewal, differentiation into tumor cells, resistance to radiation therapy and chemotherapy, and invasiveness and metastatic ability. Molecular genetic analysis using knockout animals and inducible transgenics have identified NF-κB, c-Jun, p21CIP1, and Forkhead-like-protein Dach1 in BCSC expansion and fate. Clinical analyses of BCSCs in breast tumors have found a correlation between the proportion of BCSCs and poor prognosis. Therefore, new therapies that specifically target BCSCs are an urgent need. We summarize recent evidence that partially explain the biological characteristics of BCSCs. PMID:22249027

  11. Fulvestrant and/or Anastrozole in Treating Postmenopausal Patients With Stage II-III Breast Cancer Undergoing Surgery

    ClinicalTrials.gov

    2017-09-29

    Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Recurrent Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  12. Breast and Colon Cancer Family Registries

    Cancer.gov

    The Breast Cancer Family Registry and the Colon Cancer Family Registry were established by the National Cancer Institute as a resource for investigators to use in conducting studies on the genetics and molecular epidemiology of breast and colon cancer.

  13. Update on Anti-Angiogenesis Therapy in Colorectal Cancer

    PubMed Central

    Ciombor, Kristen K.; Goldberg, Richard M.

    2016-01-01

    Angiogenesis is a complex biologic process critical to growth and proliferation of colorectal cancer. The safety and efficacy of various anti-angiogenic agents have been investigated in many treatment settings. Bevacizumab, an anti-vascular endothelial growth factor agent, has efficacy in both the first-line setting and beyond progression in metastatic colorectal cancer. The decoy vascular endothelial growth factor receptor aflibercept has been approved in combination with 5-fluorouracil, leucovorin and irinotecan-based chemotherapy in metastatic colorectal cancer patients whose disease has progressed on a prior oxaliplatin-based chemotherapy regimen. The multikinase inhibitor regorafenib is modestly effective in the refractory colorectal cancer setting but confers significant toxicity. Ramucirumab, an anti-vascular endothelial growth factor receptor 2 molecule, has efficacy in combination with 5-fluorouracil, leucovorin and irinotecan after disease progression on a first-line bevacizumab-, oxaliplatin- and fluoropyrimidine-containing regimen. Questions regarding optimal treatment setting, predictive biomarkers of response, and cost effectiveness of these anti-angiogenic agents and others are as yet unanswered. PMID:27551256

  14. Benign Breast Disease: Toward Molecular Prediction of Breast Cancer Risk

    DTIC Science & Technology

    2007-06-01

    cancer risk in women with radial scars in benign breast biopsies. Breast cancer Research and Treatment . Published online May 22, 2007... scars and involution. We explored the link between centrosome amplification, COX-2 expression and breast cancer outcomes and are currently exploring...5. Radial Scars The significance of radial scars to subsequent risk of breast cancer has been debated. Radial scars (RS) are benign breast

  15. Breast cancer patient stories project.

    PubMed

    Tanna, Nuttan; Buijs, Helene; Pitkin, Joan; Reichert, Robert

    2012-12-01

    It is estimated that there are almost half a million women living with or beyond a breast cancer diagnosis in the UK, often referred to as the breast cancer survivor population. We report on the setting up of a dedicated breast cancer and menopause symptoms service (BCMS), and present results from research undertaken with breast cancer survivors with the aim of obtaining their perspectives on the BCMS service. An action-oriented approach incorporating improvement science methodology has been used to help develop and drive changes to support a high standard of NHS patient care delivery for women with breast cancer within the BCMS setting. Evaluation was undertaken of this innovative service using qualitative methodology, and included discussion within a focus group setting, patient consent to record discussion, followed by thematic analysis of transcription. Women who have survived breast cancer identified a need for specialist support to help improve their quality of life, which is also affected by menopause type symptomology. This support can be provided within the BCMS service setting. Our recommendations are that the BCMS service model is incorporated into any regional or national breast cancer patient pathway and service redesign work in place. Breast cancer survivors would support the setting up of a BCMS service, and would actively help raise awareness and market this service.

  16. Hereditary breast cancer in Jews.

    PubMed

    Rubinstein, Wendy S

    2004-01-01

    A family history of breast cancer poses higher risks for Jewish versus non-Jewish women, particularly for early-onset breast cancer. This appears to be due in large part to the high prevalence (2.5%) of three BRCA1 and BRCA2 founder mutations in Ashkenazi Jews. About 4 to 8% of non-Jewish male breast cancer cases versus 19% of Jewish male breast cancer cases carry germline BRCA mutations. Jewish women are disproportionately impacted by BRCA mutations throughout life, with a 10% carrier rate for breast cancer diagnosed at any age and a 21 to 30% carrier rate for breast cancer diagnosed by age 40. Comparable rates in non-Jewish populations are 6.1% for breast cancer diagnosed before age 50. Lifetime penetrance estimates based on genotyping of probands have ranged widely in Jewish and non-Jewish populations. However, a study of 1008 Jewish women with breast cancer which extended genotyping to relatives found high penetrance rates with considerably smaller standard errors. This study and studies of early-onset incident breast cancer in non-Jews have found that at least half of high-risk cases would be missed by family history screening alone. While the carrier rate in non-Jewish populations is too low to consider genetic screening, the carrier rate in Ashkenazi Jews is high and genetic screening poses fewer technical barriers. The high genetic attributable cancer risks of Ashkenazi BRCA founder mutations, the sobering lethality of ovarian and early onset breast cancers, and the increasing clarity about effectiveness of medical interventions make imperative further dialogue and research to keep guidelines for genetic screening up to date.

  17. Can Smog Raise Breast Cancer Risk?

    MedlinePlus

    ... gov/news/fullstory_164495.html Can Smog Raise Breast Cancer Risk? Exposure to fine-particle air pollution linked ... have dense breasts, a known risk factor for breast cancer, new research suggests. "It appears that women who ...

  18. Treatment Option Overview (Male Breast Cancer)

    MedlinePlus

    ... spread outside the breast . In stage IB , small clusters of breast cancer cells (larger than 0.2 ... centimeters but not larger than 5 centimeters. Small clusters of breast cancer cells (larger than 0.2 ...

  19. Treatment Options for Male Breast Cancer

    MedlinePlus

    ... spread outside the breast . In stage IB , small clusters of breast cancer cells (larger than 0.2 ... centimeters but not larger than 5 centimeters. Small clusters of breast cancer cells (larger than 0.2 ...

  20. General Information about Male Breast Cancer

    MedlinePlus

    ... spread outside the breast . In stage IB , small clusters of breast cancer cells (larger than 0.2 ... centimeters but not larger than 5 centimeters. Small clusters of breast cancer cells (larger than 0.2 ...

  1. Green Tea and Breast Cancer

    PubMed Central

    Wu, Anna H; Butler, Lesley M

    2014-01-01

    The identification of modifiable lifestyle factors that could reduce the risk of breast cancer is a research priority. Despite the enormous chemo preventive potential of green tea and compelling evidence from animal studies, its role in breast cancer development in humans is still unclear. Part of the uncertainty is related to the relatively small number of epidemiological studies on green tea and breast cancer and that the overall results from case-control studies and prospective cohort studies are discordant. In addition, the mechanisms by which green tea intake may influence risk of breast cancer in humans remains not well studied. We review the human studies that have evaluated the relationship between green tea intake and four biomarkers (sex steroid hormones, mammographic density, insulin-like growth factor, adiponectin) that are believed to be important in breast cancer development. Results from these biomarker studies are also inconclusive. Limitations of human studies and areas of further investigations are discussed. PMID:21538855

  2. Radiation-induced breast cancer

    SciTech Connect

    Finnerty, N.A.; Buzdar, A.U.; Blumenschein, G.R.

    1984-06-01

    Between 1975 and 1983, sixteen patients with a history of irradiation at an early age to the head, neck, or chest areas for a variety of conditions in whom breast cancer subsequently developed were seen at out institute. The median latent period between the irradiation and the development of breast cancer was 420 months. The distribution of patients by stage of the disease and the median age at diagnosis of this subgroup was similar to the breast cancer observed in the general population. The subsequent course of this disease was also similar to the breast cancer observed in the general population. A substantial number of women have been exposed to irradiation at a young age, and these women are at a higher risk of having breast cancer develop. These women should be closely observed to discover the disease in an early curable stage.

  3. [Can breast cancer be prevented?].

    PubMed

    Vatten, L J

    1991-05-30

    More than six-fold variation in incidence between countries, an increasing incidence among immigrants to high incidence areas, and a general increase in the incidence of breast cancer within countries, are factors which suggest a potential for prevention. Reproductive factors such as early menarche, late age at first full term birth, nulliparity, and late age at menopause increase risk of breast cancer, but manipulation of any one of these factors does not seem to be a realistic preventive tool. Nevertheless, the future possibility of using tamoxifen as a chemopreventive agent against breast cancer is discussed, particularly in relation to women at increased risk due to familial clustering. Alcohol consumption by young women, and overweight among postmenopausal women may also increase the incidence of breast cancer. Consequently, reduced alcohol intake by young women, and weight reduction among overweight women after menopause may reduce the risk of breast cancer.

  4. [Therapeutic advances in breast cancer].

    PubMed

    Pestalozzi, B C

    2006-04-01

    The treatment of breast cancer has made significant improvements during the past ten years. For early breast cancer with a clinically negative axilla sentinel node biopsy has become the preferred approach. For endocrine therapy of postmenopausal patients the selective aromatase inhibitors have become standard in metastatic as well as in early breast cancer. Trastuzumab (Herceptin) plays an important role in the treatment of HER2-positive breast cancer in the metastatic and since 2005 also in the adjuvant setting. When chemotherapy is used to treat metastatic breast cancer drug combinations are superior to monotherapy only in terms of response rates. By contrast, in the adjuvant setting combination drug therapy is the standard. New methods of tissue analysis including expression patterns of mRNA and proteins are promising research strategies to further advance the field.

  5. What Are the Key Statistics about Breast Cancer in Men?

    MedlinePlus

    ... in Men What Are the Key Statistics About Breast Cancer in Men? The American Cancer Society estimates for ... Treatment in Breast Cancer in Men? More In Breast Cancer In Men About Breast Cancer in Men Causes, ...

  6. Addition of Carboplatin to Neoadjuvant Therapy for Triple-negative and HER2-positive Early Breast Cancer

    ClinicalTrials.gov

    2016-02-12

    Tubular Breast Cancer Stage II; Mucinous Breast Cancer Stage II; Breast Cancer Female NOS; Invasive Ductal Breast Cancer; Tubular Breast Cancer Stage III; HER-2 Positive Breast Cancer; Inflammatory Breast Cancer Stage IV; Inflammatory Breast Cancer

  7. Carboplatin and Combination Chemotherapy With or Without Veliparib in Treating Patients With Stage IIB-IIIC Breast Cancer

    ClinicalTrials.gov

    2017-05-10

    Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Progesterone Receptor-negative Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer

  8. Functional Magnetic Resonance Imaging in Assessing Affect Reactivity and Regulation in Patients With Stage 0-III Breast Cancer

    ClinicalTrials.gov

    2017-02-27

    Healthy Subject; 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

  9. Optimal breast cancer pathology manifesto.

    PubMed

    Tot, T; Viale, G; Rutgers, E; Bergsten-Nordström, E; Costa, A

    2015-11-01

    This manifesto was prepared by a European Breast Cancer (EBC) Council working group and launched at the European Breast Cancer Conference in Glasgow on 20 March 2014. It sets out optimal technical and organisational requirements for a breast cancer pathology service, in the light of concerns about variability and lack of patient-centred focus. It is not a guideline about how pathology services should be performed. It is a call for all in the cancer community--pathologists, oncologists, patient advocates, health administrators and policymakers--to check that services are available that serve the needs of patients in a high quality, timely way.

  10. Breast Tissue Composition and Susceptibility to Breast Cancer

    PubMed Central

    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

  11. Exercise in Targeting Metabolic Dysregulation in Stage I-III Breast or Prostate Cancer Survivors

    ClinicalTrials.gov

    2017-09-12

    Cancer Survivor; No Evidence of Disease; Obesity; Overweight; Prostate Carcinoma; Sedentary Lifestyle; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  12. Exercise Intervention in Targeting Adiposity and Inflammation With Movement to Improve Prognosis in Breast Cancer

    ClinicalTrials.gov

    2017-08-19

    Cancer Survivor; Central Obesity; Estrogen Receptor Positive; Postmenopausal; Progesterone Receptor Positive; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  13. Multiscale Models of Breast Cancer Progression

    PubMed Central

    Chakrabarti, Anirikh; Verbridge, Scott; Stroock, Abraham D.; Fischbach, Claudia; Varner, Jeffrey D.

    2013-01-01

    Breast cancer initiation, invasion and metastasis span multiple length and time scales. Molecular events at short length scales lead to an initial tumorigenic population, which left unchecked by immune action, acts at increasingly longer length scales until eventually the cancer cells escape from the primary tumor site. This series of events is highly complex, involving multiple cell types interacting with (and shaping) the microenvironment. Multiscale mathematical models have emerged as a powerful tool to quantitatively integrate the convective-diffusion-reaction processes occurring on the systemic scale, with the molecular signaling processes occurring on the cellular and subcellular scales. In this study, we reviewed the current state of the art in cancer modeling across multiple length scales, with an emphasis on the integration of intracellular signal transduction models with pro-tumorigenic chemical and mechanical microenvironmental cues. First, we reviewed the underlying biomolecular origin of breast cancer, with a special emphasis on angiogenesis. Then, we summarized the development of tissue engineering platforms which could provide highfidelity ex vivo experimental models to identify and validate multiscale simulations. Lastly, we reviewed top-down and bottom-up multiscale strategies that integrate subcellular networks with the microenvironment. We present models of a variety of cancers, in addition to breast cancer specific models. Taken together, we expect as the sophistication of the simulations increase, that multiscale modeling and bottom-up agent-based models in particular will become an increasingly important platform technology for basic scientific discovery, as well as the identification and validation of potentially novel therapeutic targets. PMID:23008097

  14. Curing Metastatic Breast Cancer.

    PubMed

    Sledge, George W

    2016-01-01

    Metastatic breast cancer is generally considered incurable, and this colors doctor-patient interactions for patients with metastatic disease. Although true for most patients, there appear to be important exceptions, instances where long-term disease-free survival occurs. Although these instances are few in number, they suggest the possibility of cure. How will we move toward cure for a much larger population of patients with metastatic disease? This article outlines a potential research agenda that might move us toward that distant goal. Copyright © 2016 by American Society of Clinical Oncology.

  15. [Breast cancer in elderly].

    PubMed

    Diab, Sami G

    2007-10-01

    The question of the breast cancer in elderly is enlightened by two constituted epidemiological data bases in the United-States: the data basis of San Antonio and the SEER (Surveillance Epidemology and End Results) which represent a follow-up of 26% of the American population. The listed data allow an approach of the clinical and biological constituents according to the age of the disease as well as the factors of comorbidity. The informations relative to the therapeutic choices are more fragmentary and must be developed first and foremost during the programs. double dagger.

  16. Inhibition of breast cancer growth and metastasis by a biomimetic peptide.

    PubMed

    Lee, Esak; Lee, Seung Jae; Koskimaki, Jacob E; Han, Zheyi; Pandey, Niranjan B; Popel, Aleksander S

    2014-11-20

    Metastasis is the main cause of mortality in cancer patients. Though there are many anti-cancer drugs targeting primary tumor growth, anti-metastatic agents are rarely developed. Angiogenesis and lymphangiogenesis are crucial for cancer progression, particularly, lymphangiogenesis is pivotal for metastasis in breast cancer. Here we report that a novel collagen IV derived biomimetic peptide inhibits breast cancer growth and metastasis by blocking angiogenesis and lymphangiogenesis. The peptide inhibits blood and lymphatic endothelial cell viability, migration, adhesion, and tube formation by targeting IGF1R and Met signals. The peptide blocks MDA-MB-231 tumor growth by inhibiting tumor angiogenesis in vivo. Moreover, the peptide inhibits lymphangiogenesis in primary tumors. MDA-MB-231 tumor conditioned media (TCM) was employed to accelerate spontaneous metastasis in tumor xenografts, and the anti-metastatic activity of the peptide was tested in this model. The peptide prevents metastasis to the lungs and lymph nodes by inhibiting TCM-induced lymphangiogenesis and angiogenesis in the pre-metastatic organs. In summary, a novel biomimetic peptide inhibits breast cancer growth and metastasis by blocking angiogenesis and lymphangiogenesis in the pre-metastatic organs as well as primary tumors.

  17. Inhibition of breast cancer growth and metastasis by a biomimetic peptide

    PubMed Central

    Lee, Esak; Lee, Seung Jae; Koskimaki, Jacob E.; Han, Zheyi; Pandey, Niranjan B.; Popel, Aleksander S.

    2014-01-01

    Metastasis is the main cause of mortality in cancer patients. Though there are many anti-cancer drugs targeting primary tumor growth, anti-metastatic agents are rarely developed. Angiogenesis and lymphangiogenesis are crucial for cancer progression, particularly, lymphangiogenesis is pivotal for metastasis in breast cancer. Here we report that a novel collagen IV derived biomimetic peptide inhibits breast cancer growth and metastasis by blocking angiogenesis and lymphangiogenesis. The peptide inhibits blood and lymphatic endothelial cell viability, migration, adhesion, and tube formation by targeting IGF1R and Met signals. The peptide blocks MDA-MB-231 tumor growth by inhibiting tumor angiogenesis in vivo. Moreover, the peptide inhibits lymphangiogenesis in primary tumors. MDA-MB-231 tumor conditioned media (TCM) was employed to accelerate spontaneous metastasis in tumor xenografts, and the anti-metastatic activity of the peptide was tested in this model. The peptide prevents metastasis to the lungs and lymph nodes by inhibiting TCM-induced lymphangiogenesis and angiogenesis in the pre-metastatic organs. In summary, a novel biomimetic peptide inhibits breast cancer growth and metastasis by blocking angiogenesis and lymphangiogenesis in the pre-metastatic organs as well as primary tumors. PMID:25409905

  18. Breast Cancer: Epidemiology and Etiology.

    PubMed

    Tao, ZiQi; Shi, Aimin; Lu, Cuntao; Song, Tao; Zhang, Zhengguo; Zhao, Jing

    2015-06-01

    Breast cancer, the most frequently occurring cancer in women, is a major public health problem, with 1,384,155 estimated new cases worldwide with nearly 459,000 related deaths. Breast cancer is highly heterogeneous in its pathological characteristics, some cases showing slow growth with excellent prognosis, while others being aggressive tumors. Current predictions and statistics suggest that both worldwide incidence of breast cancer and related mortality are on the rise. According to 2012 GLOBOCAN statistics, nearly 1.7 million women were diagnosed with breast cancer with 522,000 related deaths-an increase in breast cancer incidence and related mortality by nearly 18 % from 2008. According to American Cancer Society, one in eight women in the United States will develop breast cancer in her lifetime. It has been predicted that the worldwide incidence of female breast cancer will reach approximately 3.2 million new cases per year by 2050. These numbers reflect the magnitude of breast cancer incidence, its effect on society worldwide and the need for urgency for preventive and treatment measures. While technological advances in medical sciences and health care have made it possible to detect the disease early and to start the treatment early on to prevent the progress of the disease into a metastatic state, there are several unanswered questions with regard to the molecular mechanisms that underlie the aggressiveness of certain forms of this disease. Epidemiological studies suggest that addressing socio economical issues is utmost important, so that all women have equal access to medical care from screening to advanced treatment, and only such decisive action can help reduce the worldwide burden of breast cancer.

  19. Biomarkers in Tissue Samples From Patients With Newly Diagnosed Breast Cancer Treated With Zoledronic Acid

    ClinicalTrials.gov

    2017-06-07

    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

  20. Neo-adjuvant Therapy With Anastrozole Plus Pazopanib in Stage II and III ER+ Breast Cancer

    ClinicalTrials.gov

    2016-05-24

    Estrogen Receptor-positive Breast Cancer; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Male Breast Cancer; Recurrent Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer

  1. Features of aggressive breast cancer.

    PubMed

    Arpino, Grazia; Milano, Monica; De Placido, Sabino

    2015-10-01

    Aggressive breast cancer is a term commonly used in literature to describe breast cancer with a poor prognosis. Identifying and understanding the factors associated with aggressiveness could be helpful to the management of patients with breast cancer. Breast cancer is a heterogeneous disease, both clinically and biologically, which may be responsible for the wide range of survival durations for patients with metastatic disease. The goal of this study was to identify the factors most often described in association with aggressive metastatic breast cancer (MBC). A systematic review was performed by querying PubMed from January 1, 2012 to June 1, 2014 for "metastatic breast cancer" ("aggressive" or "poor prognosis" or "high risk"). The level of evidence to support each potential prognostic factor of aggressive MBC was also reviewed. The identified factors were grouped into 3 principle categories: clinical, biological, and patient related. Because patient-related factors may not be indicative of inherent cancer aggressiveness, this review focused only on clinical and biological factors. The factors with the highest levels of evidence to support associations with survival in metastatic breast cancer were visceral metastases, number of metastatic sites, disease-free interval, presence of CTCs, triple-negative disease, and tumour grade. Identification of these factors and understanding their contribution to the aggressiveness of MBC and disease progression may lead to more personalized treatment in this patient population. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Oncolytic virotherapy of breast cancer.

    PubMed

    Hartkopf, Andreas D; Fehm, Tanja; Wallwiener, Diethelm; Lauer, Ulrich M

    2011-10-01

    The use of replication competent viruses that selectively target and destroy cancer cells has rapidly evolved over the past decade and numerous innovative oncolytic viruses have been created. Many of these promising anti-cancer agents have recently entered into clinical trials (including those on breast cancer) and demonstrated encouraging safety and efficacy. Virotherapeutic strategies are thus of considerable interest to combat breast cancer in both (i) the primary disease situation in which relapse should be avoided as good as possible and (ii) in the metastatic situation which remains incurable to date. Here, we summarize data from preclinical and clinical trials using oncolytic virotherapy to treat breast cancer. This includes strategies to specifically target breast cancer cells, to arm oncolytic viruses with additional therapeutic transgenes and an outlining of future challenges when translating these promising therapeutics "from bench to bedside".

  3. Molecular basis of breast cancer.

    PubMed

    Al-Mansouri, Layla J; Alokail, Majed S

    2006-01-01

    Breast cancer is the most frequent cancer in women and represents the second leading cause of cancer death among women after lung cancer. A common phenotypic abnormality of breast cancer cells is dysregulation of cell cycle control. The transformation of normal cell to a cancer cell appears to depend on mutation in genes that normally control cell cycle progression, thus leading to loss of the regulatory cell growth. We summarize here the molecular regulation of mammary carcinoma with regards to the most prominent oncogenes and tumor suppressor genes and their outcome in terms of cellular prognosis, and tumor development.

  4. Aluminium, antiperspirants and breast cancer.

    PubMed

    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.

  5. Approach to inflammatory breast cancer

    PubMed Central

    Molckovsky, Andrea; Fitzgerald, Barbara; Freedman, Orit; Heisey, Ruth; Clemons, Mark

    2009-01-01

    Abstract OBJECTIVE To review the definition, clinical presentation, and management of inflammatory breast cancer in primary care. SOURCES OF INFORMATION Relevant research and review articles, as well as personal experience of the authors practising in a specialized locally advanced breast cancer program at a comprehensive cancer centre. Evidence is levels II and III. MAIN MESSAGE Inflammatory breast cancer is a rare disease that typically presents with a rapidly enlarging erythematous breast, often with no discernable breast mass. Identification of warning signs and recognition of clinical symptoms are crucial to prompt diagnosis and appropriate referral. Management in the primary care setting includes treatment of symptoms, psychosocial support, regular surveillance and follow-up, as well as palliative care. CONCLUSION Family physicians are usually the entry point to the health care system and are well positioned to assess inflammation of the breast and recognize the warning signs of an underlying inflammatory breast cancer. They are also important members of the team that provides support for breast cancer patients and their families during treatment, follow-up, and end-of-life care. PMID:19155362

  6. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Time-lapse exposure depicts Bioreactor rotation. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues.

  7. Breast Cancer Center Support Grant

    DTIC Science & Technology

    1999-09-01

    may make potential referral candidates more receptive when medical professionals approach them about being tested. Currently, there are barriers to...1985;253:1908-13. (39) Parazzini F, La Vecchia C, Negri E, Franceschi S, Tozzi L. Family history of breast, ovarian and endometrial cancer and risk of...Raloxifene reduces the risk of breast cancer and may decrease the risk of endometrial cancer in post- menopausal women. Two year findings from the

  8. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Time-lapse exposure depicts Bioreactor rotation. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues.

  9. The Biology of Breast Cancer Metastasis

    DTIC Science & Technology

    2002-10-01

    Breast cancer is the second most common cause of brain metastases, diagnosed in 10 to 15% of breast cancer patients and found at autopsy in 20 to 30...Relatively little is known about how breast cancer cells metastasize to the brain , and what phenotypes characterize these cells. This is due in...breast cancer brain metastases, using intra-carotid artery injection of breast cancer cells into nude mice.

  10. Copanlisib, Letrozole, and Palbociclib in Treating Patients With Hormone Receptor Positive HER2 Negative Stage I-IV Breast Cancer

    ClinicalTrials.gov

    2017-08-17

    Estrogen Receptor Positive; HER2/Neu Negative; Invasive Breast Carcinoma; Multifocal Breast Carcinoma; Postmenopausal; Progesterone Receptor Positive; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  11. Inhibitors of Angiogenesis in Cancer Therapy - Synthesis and Biological Activity.

    PubMed

    Gensicka, Monika; Głowacka, Agnieszka; Dzierzbicka, Krystyna; Cholewinski, Grzegorz

    2015-01-01

    Angiogenesis is the process of formation of new capillaries from preexisting blood vessels. Angiogenesis is involved in normal physiological processes, and plays an important role in tumor invasion and development of metastases. Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis. VEGF is a mitogen for vascular endothelial cells and stimulates their proliferation. By inhibiting the biological activity of VEGF, and then signal cascades with neutralizing VEGF antibodies and signal inhibitors, may negatively regulate the growth and metastasis. Anti-angiogenesis therapy is less toxic than chemotherapy. Angiogenesis is a multistep and multifactorial process, and therefore, can be blocked at different levels. In this review article, the authors present the synthesis of novel inhibitors of angiogenesis, together with the results of biological tests in vitro, and in some cases, state trials.

  12. Mast Cell Tryptase Contributes to Pancreatic Cancer Growth through Promoting Angiogenesis via Activation of Angiopoietin-1.

    PubMed

    Guo, Xiangjie; Zhai, Liqin; Xue, Ruobing; Shi, Jieru; Zeng, Qiang; Gao, Cairong

    2016-05-27

    Pancreatic cancer is a highly lethal malignancy and one of the leading causes of cancer-related death. During the development and progression of cancer, tumor angiogenesis plays a crucial role. A great deal of evidence has revealed that human mast cells (MCs) contributed to tumor angiogenesis through releasing several pro-angiogenetic factors, among which tryptase is one of the most active. However, the role of mast cell tryptase (MCT) in human pancreatic cancer angiogenesis is still not well documented. In this study, we examined the MCT levels in serum from pancreatic cancer patients and evaluated the correlationship of the MCT level and tumor angiogenesis. In addition, the effect of MCT on endothelial cell proliferation and tube formation was investigated both in vitro and in nude mice bearing pancreatic tumor. It was found that MCT contributes to endothelial cell growth and tube formation via up-regulation of angiopoietin-1 expression. Moreover, using the MCT inhibitor nafamostat, tryptase-induced angiogenesis was obviously suppressed both in vitro and in vivo. Our findings suggest that MCT plays an important role in pancreatic cancer angiogenesis and tumor growth via activating the angiopoietin-1 pathway, and tryptase inhibitors may be evaluated as an effective anti-angiogenetic approach in pancreatic cancer therapy.

  13. RUNX3 inhibits the metastasis and angiogenesis of colorectal cancer.

    PubMed

    Kim, Bo Ram; Kang, Myoung Hee; Kim, Jung Lim; Na, Yoo Jin; Park, Seong Hye; Lee, Sun Il; Kang, Sanghee; Joung, Sung Yup; Lee, Suk-Young; Lee, Dae-Hee; Min, Byung Wook; Oh, Sang Cheul

    2016-11-01

    Recent studies have determined that inactivation of runt‑related transcription factor 3 (RUNX3) expression is highly associated with lymph node metastasis and poor prognosis in various types of cancer. However, the mechanism of RUNX3-mediated suppression of tumor metastasis remains unclear. Herein, we aimed to clarify the effect of RUNX3 on metastasis and angiogenesis in colorectal cancer (CRC). Firstly, we found that the reduction in expression of RUNX3 in CRC tissues when compared with tumor adjacent normal colon tissues, as indicated by reduced RUNX3 staining, was significantly correlated with tumor-node-metastasis (TNM) stage. Secondly, we demonstrated that RUNX3 overexpression inhibited CRC cell migration and invasion resulting from the upregulation of matrix metalloproteinase-2 (MMP-2) and MMP-9 expression. In contrast, the knockdown of RUNX3 reduced the inhibition of migration and invasion of CRC cells. Finally, we found that restoration of RUNX3 decreased vascular endothelial growth factor (VEGF) secretion and suppressed endothelial cell growth and tube formation in CRC cells. All in all, our findings may provide insight into the development of RUNX3 for CRC metastasis diagnostics and therapeutics.

  14. Adjuvant Anti-Angiogenesis Drugs Are No Benefit in Kidney Cancer

    Cancer.gov

    Results from a recent clinical trial show that post-surgical therapy with two anti-angiogenesis drugs does not improve progression-free survival for patients with kidney cancer and may cause serious side effects.

  15. Tissue-engineered 3D tumor angiogenesis models: potential technologies for anti-cancer drug discovery.

    PubMed

    Chwalek, Karolina; Bray, Laura J; Werner, Carsten

    2014-12-15

    Angiogenesis is indispensable for solid tumor expansion, and thus it has become a major target of cancer research and anti-cancer therapies. Deciphering the arcane actions of various cell populations during tumor angiogenesis requires sophisticated research models, which could capture the dynamics and complexity of the process. There is a continuous need for improvement of existing research models, which engages interdisciplinary approaches of tissue engineering with life sciences. Tireless efforts to develop a new model to study tumor angiogenesis result in innovative solutions, which bring us one step closer to decipher the dubious nature of cancer. This review aims to overview the recent developments, current limitations and future challenges in three-dimensional tissue-engineered models for the study of tumor angiogenesis and for the purpose of elucidating novel targets aimed at anti-cancer drug discovery.

  16. Family History of Breast Cancer, Breast Density, and Breast Cancer Risk in a U.S. Breast Cancer Screening Population.

    PubMed

    Ahern, Thomas P; Sprague, Brian L; Bissell, Michael C S; Miglioretti, Diana L; Buist, Diana S M; Braithwaite, Dejana; Kerlikowske, Karla

    2017-06-01

    Background: The utility of incorporating detailed family history into breast cancer risk prediction hinges on its independent contribution to breast cancer risk. We evaluated associations between detailed family history and breast cancer risk while accounting for breast density.Methods: We followed 222,019 participants ages 35 to 74 in the Breast Cancer Surveillance Consortium, of whom 2,456 developed invasive breast cancer. We calculated standardized breast cancer risks within joint strata of breast density and simple (1(st)-degree female relative) or detailed (first-degree, second-degree, or first- and second-degree female relative) breast cancer family history. We fit log-binomial models to estimate age-specific breast cancer associations for simple and detailed family history, accounting for breast density.Results: Simple first-degree family history was associated with increased breast cancer risk compared with no first-degree history [Risk ratio (RR), 1.5; 95% confidence interval (CI), 1.0-2.1 at age 40; RR, 1.5; 95% CI, 1.3-1.7 at age 50; RR, 1.4; 95% CI, 1.2-1.6 at age 60; RR, 1.3; 95% CI, 1.1-1.5 at age 70). Breast cancer associations with detailed family history were strongest for women with first- and second-degree family history compared with no history (RR, 1.9; 95% CI, 1.1-3.2 at age 40); this association weakened in higher age groups (RR, 1.2; 95% CI, 0.88-1.5 at age 70). Associations did not change substantially when adjusted for breast density.Conclusions: Even with adjustment for breast density, a history of breast cancer in both first- and second-degree relatives is more strongly associated with breast cancer than simple first-degree family history.Impact: Future efforts to improve breast cancer risk prediction models should evaluate detailed family history as a risk factor. Cancer Epidemiol Biomarkers Prev; 26(6); 938-44. ©2017 AACR. ©2017 American Association for Cancer Research.

  17. The Emerging Regulation of VEGFR-2 in Triple-Negative Breast Cancer

    PubMed Central

    Zhu, Xiaoxia; Zhou, Wen

    2015-01-01

    Vascular endothelial growth factor-A (VEGF) signals vascular development and angiogenesis mainly by binding to VEGF receptor family member 2 (VEGFR-2). Adaptor proteins mediate many VEGFR-2’s functions in the development of blood vessels. Cancer cells secrete VEGF to activate VEGFR-2 pathway in their neighboring endothelial cells in the process of cancer-related angiogenesis. Interestingly, activation of VEGFR-2 signaling is found in breast cancer cells, but its role and regulation are not clear. We highlighted research advances of VEGFR-2, with a focus on VEGFR-2’s regulation by mutant p53 in breast cancer. In addition, we reviewed recent Food and Drug Administration-approved tyrosine kinase inhibitor drugs that can inhibit the function of VEGFR-2. Ongoing preclinical and clinical studies might prove that pharmaceutically targeting VEGFR-2 could be an effective therapeutic strategy in treating triple-negative breast cancer. PMID:26500608

  18. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Human primary breast tumor cells after 56 days of culture in a NASA Bioreactor. A cross-section of a construct, grown from surgical specimens of brease cancer, stained for microscopic examination, reveals areas of tumor cells dispersed throughout the non-epithelial cell background. The arrow denotes the foci of breast cancer cells. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Jearne Becker, University of South Florida

  19. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Human primary breast tumor cells after 56 days of culture in a NASA Bioreactor. A cross-section of a construct, grown from surgical specimens of brease cancer, stained for microscopic examination, reveals areas of tumor cells dispersed throughout the non-epithelial cell background. The arrow denotes the foci of breast cancer cells. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Jearne Becker, University of South Florida

  20. Promising molecular targeted therapies in breast cancer

    PubMed Central

    Munagala, Radha; Aqil, Farrukh; Gupta, Ramesh C.

    2011-01-01

    In recent years, there has been a significant improvement in the understanding of molecular events and critical pathways involved in breast cancer. This has led to the identification of novel targets and development of anticancer therapies referred to as targeted therapy. Targeted therapy has high specificity for the molecules involved in key molecular events that are responsible for cancer phenotype such as cell growth, survival, migration, invasion, metastasis, apoptosis, cell-cycle progression, and angiogenesis. Targeted agents that have been approved for breast cancer include trastuzumab and lapatinib, directed against human epidermal growth factor receptor 2 (HER2) and bevacizumab, directed against vascular endothelial growth factor (VEGF). Several other targeted agents currently under evaluation in preclinical and clinical trials include inhibitors of epidermal growth factor receptor (EGFR), dual EGFR and HER2 inhibitors, VEGF/VEGFR inhibitors, and agents that interfere with crucial signaling pathways such as PI3K/AKT/mTOR and RAS/MEK/ERK; agents against other tyrosine kinases such as Src, insulin-like growth factor (IGF)/IGF-receptor (IGFR); agents that promote apoptosis such as Poly ADP ribose polymerase inhibitors; agents that target invasion and metastasis such as matrix metalloproteinases inhibitors and others. In this review, we highlight the most promising targeted agents and their combination with mainstream chemotherapeutic drugs in clinical trials. PMID:21713084

  1. Promising molecular targeted therapies in breast cancer.

    PubMed

    Munagala, Radha; Aqil, Farrukh; Gupta, Ramesh C

    2011-05-01

    In recent years, there has been a significant improvement in the understanding of molecular events and critical pathways involved in breast cancer. This has led to the identification of novel targets and development of anticancer therapies referred to as targeted therapy. Targeted therapy has high specificity for the molecules involved in key molecular events that are responsible for cancer phenotype such as cell growth, survival, migration, invasion, metastasis, apoptosis, cell-cycle progression, and angiogenesis. Targeted agents that have been approved for breast cancer include trastuzumab and lapatinib, directed against human epidermal growth factor receptor 2 (HER2) and bevacizumab, directed against vascular endothelial growth factor (VEGF). Several other targeted agents currently under evaluation in preclinical and clinical trials include inhibitors of epidermal growth factor receptor (EGFR), dual EGFR and HER2 inhibitors, VEGF/VEGFR inhibitors, and agents that interfere with crucial signaling pathways such as PI3K/AKT/mTOR and RAS/MEK/ERK; agents against other tyrosine kinases such as Src, insulin-like growth factor (IGF)/IGF-receptor (IGFR); agents that promote apoptosis such as Poly ADP ribose polymerase inhibitors; agents that target invasion and metastasis such as matrix metalloproteinases inhibitors and others. In this review, we highlight the most promising targeted agents and their combination with mainstream chemotherapeutic drugs in clinical trials.

  2. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Human primary breast tumor cells after 49 days of growth in a NASA Bioreactor. Tumor cells aggregate on microcarrier beads (indicated by arrow). NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Jearne Becker, University of South Florida

  3. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    High magnification of view of tumor cells aggregate on microcarrier beads, illustrting breast cells with intercellular boundaires on bead surface and aggregates of cells achieving 3-deminstional growth outward from bead after 56 days of culture in a NASA Bioreactor. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Jearne Becker, University of South Florida.

  4. Adjuvant therapy of breast cancer.

    PubMed

    Davidson, N E; Abeloff, M D

    1994-01-01

    About 180,000 American women will be diagnosed with early stage breast cancer during 1993. In many of these patients breast cancer is a systemic disease at diagnosis and thus not curable by local treatment alone. The development of optimal forms of systemic adjuvant therapy has been a major area of research for more than 30 years. The two most widely employed types of adjuvant therapy, cytotoxic chemotherapy and tamoxifen, have been shown to improve relapse-free and overall survival in certain patient subsets. This review highlights recent advances in adjuvant therapy of early stage breast cancer and discusses current treatment guidelines.

  5. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    High magnification of view of tumor cells aggregate on microcarrier beads, illustrting breast cells with intercellular boundaires on bead surface and aggregates of cells achieving 3-deminstional growth outward from bead after 56 days of culture in a NASA Bioreactor. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Jearne Becker, University of South Florida.

  6. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Human primary breast tumor cells after 49 days of growth in a NASA Bioreactor. Tumor cells aggregate on microcarrier beads (indicated by arrow). NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Jearne Becker, University of South Florida

  7. Progress in breast cancer: overview.

    PubMed

    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. ©2013 AACR.

  8. Antiperspirants/Deodorants and Breast Cancer

    MedlinePlus

    ... Directory Cancer Prevention Overview Research Antiperspirants/Deodorants and Breast Cancer On This Page Is there a link between antiperspirants or deodorants and breast cancer? What is known about the ingredients in antiperspirants ...

  9. Breast Cancer Chemotherapy and Your Heart

    MedlinePlus

    ... of the American Heart Association Cardiology Patient Page Breast Cancer Chemotherapy and Your Heart Christine Unitt , Kamaneh Montazeri , ... Disclosures Footnotes Figures & Tables Info & Metrics eLetters Introduction Breast cancer is the most commonly diagnosed cancer in women. ...

  10. Breast Cancer In Women Infographic

    Cancer.gov

    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.

  11. Targeting Breast Cancer Stem Cells In Triple Negative Breast Cancer

    DTIC Science & Technology

    2014-10-01

    breast cancer (TNBC) and drug resistance. We hypothesize that obesity effects on TNBC occur via leptin -signaling stimulation of breast cancer stem...human TNBC cell lines treated with leptin , and novel leptin receptor inhibitor bound to nanoparticles (IONPs-LPrA) alone, and combined with cisplatin...a chemotherapeutic) and Sunitinib (an inhibitor of VEGFR-2 kinase). Our data show that leptin increased cell proliferation and expression of BCSC

  12. Doxorubicin Hydrochloride, Cyclophosphamide, and Filgrastim Followed By Paclitaxel Albumin-Stabilized Nanoparticle Formulation With or Without Trastuzumab in Treating Patients With Breast Cancer Previously Treated With Surgery

    ClinicalTrials.gov

    2013-05-07

    Estrogen Receptor-positive Breast Cancer; HER2-positive 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

  13. Vitamin D and Breast Cancer

    DTIC Science & Technology

    1995-07-15

    Sadler M, Vollmer RT, Lobaugh B, Drezner MK, Vogelman JH, Orentreich N. Vitamin D and prostate cancer: a prediagnostic study with stored sera. Cancer ... Epidemiology , Biomarkers & Prevention 2:467-472,1993. 6. Blot WJ, Fraumeni JF, Stone BJ. Geographic patterns of breast cancer in the United States. J

  14. Aromatase and breast cancer.

    PubMed

    Brodie, A; Sabnis, G; Jelovac, D

    2006-12-01

    Several aromatase inhibitors and also new antiestrogens are now available for treating breast cancer. We have developed a model to compare the antitumor efficacy of these agents and to explore strategies for their optimal use. Results from the model have been predictive of clinical outcome. In this model, tumors are grown in ovariectomized, immunodeficient mice from MCF-7 human breast cancer cells transfected with the aromatase gene (MCF-7Ca). The possibility that blockade of estrogen action and estrogen synthesis may be synergistic was explored by treating mice with the aromatase inhibitor letrozole and the antiestrogen tamoxifen alone and in combination. The results indicated that letrozole alone was better than all other treatments. In addition, when tamoxifen treatment was no longer effective, tumor growth was significantly reduced in mice switched to letrozole treatment. However, tumors ultimately began to grow during continued treatment. To investigate the mechanisms by which tumors eventually adapt and grow during letrozole treatment, we determined the expression of signaling proteins in tumors during the course of letrozole treatment compared to the tumors of control mice. Tumors initially up-regulated the ER while responding to treatment, but subsequently receptor levels decreased in tumors unresponsive to letrozole. Also, Her-2 and adapter proteins (p-Shc and Grb-2) as well as all of the signaling proteins in the MAPK cascade (p-Raf, p-Mekl/2, and p-MAPK), but not in the Pl3/Akt pathway, were increased in tumors no longer responsive to letrozole. To investigate whether sensitivity to letrozole could be regained, cells were isolated from the letrozole resistant tumors (LTLT) and treated with inhibitors of the MAPKinase pathway (PD98059 and UO126). These compounds reduced MAPK activity and increased ER expression. EGFR/Her-2 inhibitors, gefitinib and AEE78S although not effective in the parental MCF-70a cells, restored the sensitivity of LTLT cells to

  15. Do We Know What Causes Breast Cancer in Men?

    MedlinePlus

    ... Factors, and Prevention Do We Know What Causes Breast Cancer in Men? Although certain risk factors may increase ... Breast Cancer in Men Be Prevented? More In Breast Cancer In Men About Breast Cancer in Men Causes, ...

  16. Soy Isoflavones Supplementation in Treating Women at High Risk For or With Breast Cancer

    ClinicalTrials.gov

    2017-04-08

    BRCA1 Mutation Carrier; BRCA2 Mutation Carrier; Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer

  17. Onalespib and Paclitaxel in Treating Patients With Advanced Triple Negative Breast Cancer

    ClinicalTrials.gov

    2017-02-02

    Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  18. Pembrolizumab and Binimetinib in Treating Patients With Locally Advanced or Metastatic Triple Negative Breast Cancer

    ClinicalTrials.gov

    2017-09-27

    Breast Adenocarcinoma; Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  19. Consumer Health Education. Breast Cancer.

    ERIC Educational Resources Information Center

    Arkansas Univ., Fayetteville, Cooperative Extension Service.

    This short booklet is designed to be used by health educators when teaching women about breast cancer and its early detection and the procedure for breast self-examination. It includes the following: (1) A one-page teaching plan consisting of objectives, subject matter, methods (including titles of films and printed materials), target audience,…

  20. The Angiogenic Secretome in VEGF overexpressing Breast Cancer Xenografts

    PubMed Central

    Dore-Savard, Louis; Lee, Esak; Kakkad, Samata; Popel, Aleksander S.; Bhujwalla, Zaver M.

    2016-01-01

    The plasticity of cancer cells and the fluidity of the tumor microenvironment continue to present major challenges in the comprehensive understanding of cancer that is essential to design effective treatments. The tumor interstitial fluid (TIF) encompasses the secretome and holds the key to several of the phenotypic characteristics of cancer. Difficulties in sampling this fluid have resulted in limited characterization of its components. Here we have sampled TIF from triple negative and estrogen receptor (ER)-positive human breast tumor xenografts with or without VEGF overexpression. Angiogenesis-related factors were characterized in the TIF and plasma, to understand the relationship between the TIF and plasma secretomes. Clear differences were observed between the TIF and plasma angiogenic secretomes in triple negative MDA-MB-231 breast cancer xenografts compared to ER-positive MCF-7 xenografts with or without VEGF overexpression that provide new insights into TIF components and the role of VEGF in modifying the angiogenic secretome. PMID:27995973

  1. Triiodothyronine and breast cancer

    PubMed Central

    De Sibio, Maria Teresa; de Oliveira, Miriane; Moretto, Fernanda Cristina Fontes; Olimpio, Regiane Marques Castro; Conde, Sandro José; Luvizon, Aline Carbonera; Nogueira, Célia Regina

    2014-01-01

    The thyroid hormones (THs), triiodothyronine (T3) and thyroxine (T4), are essential for survival; they are involved in the processes of development, growth, and metabolism. In addition to hyperthyroidism or hypothyroidism, THs are involved in other diseases. The role of THs in the development and differentiation of mammary epithelium is well established; however, their specific role in the pathogenesis of breast cancer (BC) is controversial. Steroid hormones affect many human cancers and the abnormal responsiveness of the mammary epithelial cells to estradiol (E2) in particular is known to be an important cause for the development and progression of BC. The proliferative effect of T3 has been demonstrated in various types of cancer. In BC cell lines, T3 may foster the conditions for tumor proliferation and increase the effect of cell proliferation by E2; thus, T3 may play a role in the development and progression of BC. Studies show that T3 has effects similar to E2 in BC cell lines. Despite controversy regarding the relationship between thyroid disturbances and the incidence of BC, studies show that thyroid status may influence the development of tumor, proliferation and metastasis. PMID:25114863

  2. Triiodothyronine and breast cancer.

    PubMed

    De Sibio, Maria Teresa; de Oliveira, Miriane; Moretto, Fernanda Cristina Fontes; Olimpio, Regiane Marques Castro; Conde, Sandro José; Luvizon, Aline Carbonera; Nogueira, Célia Regina

    2014-08-10

    The thyroid hormones (THs), triiodothyronine (T3) and thyroxine (T4), are essential for survival; they are involved in the processes of development, growth, and metabolism. In addition to hyperthyroidism or hypothyroidism, THs are involved in other diseases. The role of THs in the development and differentiation of mammary epithelium is well established; however, their specific role in the pathogenesis of breast cancer (BC) is controversial. Steroid hormones affect many human cancers and the abnormal responsiveness of the mammary epithelial cells to estradiol (E2) in particular is known to be an important cause for the development and progression of BC. The proliferative effect of T3 has been demonstrated in various types of cancer. In BC cell lines, T3 may foster the conditions for tumor proliferation and increase the effect of cell proliferation by E2; thus, T3 may play a role in the development and progression of BC. Studies show that T3 has effects similar to E2 in BC cell lines. Despite controversy regarding the relationship between thyroid disturbances and the incidence of BC, studies show that thyroid status may influence the development of tumor, proliferation and metastasis.

  3. Survivorship Care Plan in Promoting Physical Activity in Breast or Colorectal Cancer Survivors in Wisconsin

    ClinicalTrials.gov

    2017-05-01

    Cancer Survivor; Healthy Subject; Stage I Colorectal Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer; Stage IIC Colorectal Cancer; Stage IIIA Breast Cancer; Stage IIIA Colorectal Cancer; Stage IIIB Breast Cancer; Stage IIIB Colorectal Cancer; Stage IIIC Breast Cancer; Stage IIIC Colorectal Cancer

  4. Association of Breast Cancer Risk loci with Breast Cancer Survival

    PubMed Central

    Barrdahl, Myrto; Canzian, Federico; Lindström, Sara; Shui, Irene; Black, Amanda; Hoover, Robert N.; Ziegler, Regina G.; Buring, Julie E.; Chanock, Stephen J.; Diver, W. Ryan; Gapstur, Susan M.; Gaudet, Mia M.; Giles, Graham G.; Haiman, Christopher; Henderson, Brian E.; Hankinson, Susan; Hunter, David J.; Joshi, Amit D.; Kraft, Peter; Lee, I-Min; Le Marchand, Loic; Milne, Roger L.; Southey, Melissa C.; Willett, Walter; Gunter, Marc; Panico, Salvatore; Sund, Malin; Weiderpass, Elisabete; Sánchez, María-José; Overvad, Kim; Dossus, Laure; Peeters, Petra H; Khaw, Kay-Tee; Trichopoulos, Dimitrios; Kaaks, Rudolf; Campa, Daniele

    2015-01-01

    The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of evidence suggest that alleles influencing breast cancer risk might also be associated with breast cancer survival. We examined the associations between 35 breast cancer susceptibility loci and the disease over-all survival (OS) in 10,255 breast cancer patients from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer. We also conducted a meta-analysis of almost 35,000 patients and 5,000 deaths, combining results from BPC3 and the Breast Cancer Association Consortium (BCAC) and performed in silico analyses of SNPs with significant associations. In BPC3, the C allele of LSP1-rs3817198 was significantly associated with improved OS (HRper-allele=0.70; 95% CI: 0.58–0.85; Ptrend=2.84×10−4; HRheterozygotes=0.71; 95% CI: 0.55–0.92; HRhomozygotes=0.48; 95% CI: 0.31–0.76; P2DF=1.45×10−3). In silico, the C allele of LSP1-rs3817198 was predicted to increase expression of the tumor suppressor cyclin-dependent kinase inhibitor 1C (CDKN1C). In the meta-analysis, TNRC9-rs3803662 was significantly associated with increased death hazard (HRMETA =1.09; 95% CI: 1.04–1.15; Ptrend=6.6×10−4; HRheterozygotes=0.96 95% CI: 0.90–1.03; HRhomozygotes= 1.21; 95% CI: 1.09–1.35; P2DF=1.25×10−4). In conclusion, we show that there is little overlap between the breast cancer risk single nucleotide polymorphisms (SNPs) identified so far and the SNPs associated with breast cancer prognosis, with the possible exceptions of LSP1-rs3817198 and TNRC9-rs3803662. PMID:25611573

  5. Studying the influence of angiogenesis in in vitro cancer model systems.

    PubMed

    Roudsari, Laila C; West, Jennifer L

    2016-02-01

    Tumor angiogenesis is a hallmark of cancer that has been identified as a critical component of cancer progression, facilitating rapid tumor growth and metastasis. Anti-angiogenic therapies have exhibited only modest clinical success, highlighting a need for better models that can be used to gain a more thorough understanding of tumor angiogenesis and screen potential therapeutics more accurately. This review explores how recent progress in in vitro cancer and vascular models individually can be applied to the development of in vitro tumor angiogenesis models. Current in vitro tumor angiogenesis models are also discussed, with a focus on aspects of the process that have been successfully recapitulated and opportunities for applying new technologies to expand model complexity to better represent the tumor microenvironment. Continued advances in vascularized tumor models will provide tools to identify novel therapeutic targets and validate their therapeutic benefit.

  6. Treatment Option Overview (Breast Cancer)

    MedlinePlus

    ... in lymph and help fight infection and disease. Clusters of lymph nodes are found near the breast ... the tumor is 2 centimeters or smaller. Small clusters of cancer cells (larger than 0.2 millimeter ...

  7. General Information about Breast Cancer

    MedlinePlus

    ... in lymph and help fight infection and disease. Clusters of lymph nodes are found near the breast ... the tumor is 2 centimeters or smaller. Small clusters of cancer cells (larger than 0.2 millimeter ...

  8. Palbociclib for Advanced Breast Cancer

    Cancer.gov

    An interim analysis of the PALOMA3 trial shows that women with hormone receptor-positive metastatic breast cancer who received palbociclib plus fulvestrant had longer progression-free survival rates than women who received a placebo plus fulvestrant.

  9. Fostering early breast cancer detection.

    PubMed

    Shackelford, Judy A; Weyhenmeyer, Diana P; Mabus, Linda K

    2014-12-01

    This article examines how faith community nurses (FCNs) fostered early breast cancer detection for those at risk in rural and African American populations throughout nine counties in midwestern Illinois to decrease breast cancer disparities. Flexible methods for breast cancer awareness education through FCNs, effective strategies for maximizing participation, and implications for practice were identified. In addition, networking within faith communities, connecting with complementary activities scheduled in those communities, and offering refreshments and gift items that support educational efforts were identified as effective ways of maximizing outcomes and reinforcing learning. Flexible educational programming that could be adapted to situational and learning needs was important to alleviate barriers in the project. As a result, the number of participants in the breast cancer awareness education program exceeded the grant goal, and the large number of African American participants and an unexpected number of Hispanic and Latino participants exceeded the target.

  10. Tumour markers in breast cancer.

    PubMed Central

    Cove, D. H.; Woods, K. L.; Smith, S. C.; Burnett, D.; Leonard, J.; Grieve, R. J.; Howell, A.

    1979-01-01

    The clinical usefulness of 8 potential tumour markers has been evaluated in 69 patients with Stage I and II breast cancer and 57 patients with Stage III and IV. Serum CEA concentrations were raised in 13% of patients with local and 65% of those with advanced breast cancer. In patients with clinical evidence of progression or regression of tumour, serum CEA levels changed appropriately in 83% of cases. Taking 4 of the markers (carcinoembryonic antigen (CEA), lactalbumin, alpha subunit and haptoglobin) serum concentrations of one or more were raised in 33% of patients with local disease and 81% of those with advanced breast cancer. However, marker concentrations were often only marginally raised, and are unlikely to provide sensitive guide to tumour burden. CEA, lactalbumin and alpha subunit were detectable in 68%, 43% and 40% respectively of extracts of primary breast cancers. PMID:92331

  11. Breast cancer. Part 3: advanced cancer and psychological implications.

    PubMed

    Harmer, Victoria

    This is the last article in this 3-part series on breast cancer. The previous two articles have outlined the principles behind breast awareness and breast health, detailing common benign breast diseases, types of breast cancer and staging, and treatment for breast cancer, including surgery, chemotherapy, radiotherapy and endocrine treatment. The series concludes by giving information on advanced disease, including when a patient presents late with a fungating breast lesion, or if the disease has metastasized from the breast to other organs. Lymphoedema is also described and discussed, and the latter half of this article discusses psychological implications of breast cancer, from diagnosis through the individual treatments.

  12. Metals and Breast Cancer

    PubMed Central

    Byrne, Celia; Divekar, Shailaja D.; Storchan, Geoffrey B.; Parodi, Daniela A.; Martin, Mary Beth

    2014-01-01

    Metalloestrogens are metals that activate the estrogen receptor in the absence of estradiol. The metalloestrogens fall into two subclasses: metal/metalloid anions and bivalent cationic metals. The metal/metalloid anions include compounds such as arsenite, nitrite, selenite, and vanadate while the bivalent cations include metals such as cadmium, calcium, cobalt, copper, nickel, chromium, lead, mercury, and tin. The best studied metalloestrogen is cadmium. It is a heavy metal and a prevalent environmental contaminant with no known physiological function. This review addresses our current understanding of the mechanism by which cadmium and the bivalent cationic metals activate estrogen receptor-α. The review also summarizes the in vitro and in vivo evidence that cadmium functions as an estrogen and the potential role of cadmium in breast cancer. PMID:23338949

  13. Effect of AURKA Gene Expression Knockdown on Angiogenesis and Tumorigenesis of Human Ovarian Cancer Cell Lines.

    PubMed

    Wang, Cong; Yan, Qin; Hu, Minmin; Qin, Di; Feng, Zhenqing

    2016-12-01

    Ovarian cancer is one of the most common malignant gynecological cancers. Higher expression of AURKA has been found in immortalized human ovarian epithelial cells in previous studies, implying the relationship between AURKA and ovarian cancer pathogenesis. We investigated the effect of AURKA on angiogenesis and tumorigenesis of human ovarian cancer cells. Firstly, the expression of AURKA in HO8910 and SKOV3 ovarian cancer cell lines was knocked down using a vector expressing a short hairpin small interfering RNA (shRNA). Next, the effect of knockdown of AURKA on cell angiogenesis, proliferation, migration, and invasion was determined by microtubule formation assay, proliferation assay, transwell migration, and invasion assays. In addition, the effect of AURKA knockdown on angiogenesis and tumorigenesis was also determined in a chicken chorioallantoic membrane (CAM) model and in nude mice. The results of the microtubule formation assay indicated that knockdown of AURKA significantly inhibited ovarian cancer cell-induced angiogenesis of endothelial cells compared to its control (P < 0.001). Knockdown of AURKA also significantly inhibited cell proliferation, migration, and invasion of HO8910 and SKOV3 cells in vitro. Furthermore, the Matrigel plug assay showed that knockdown of AURKA significantly repressed ovarian cancer cell-induced angiogenesis in nude mice (P < 0.05), and the CAMs model also showed that AURKA knockdown significantly attenuated the angiogenesis (P < 0.001) and tumorigenesis (P < 0.001) of HO8910 cells compared to the control. Finally, the tumorigenicity assay in vivo further indicated that AURKA shRNA reduced tumorigenesis in nude mice inoculated with ovarian cancer cells (P < 0.001). These results suggest the potential role of AURKA in angiogenesis and tumorigenesis of ovarian cancer, which may provide a potential therapeutic target for the disease.

  14. High-grade ovarian cancer secreting effective exosomes in tumor angiogenesis.

    PubMed

    Yi, Huan; Ye, Jun; Yang, Xiao-Mei; Zhang, Li-Wen; Zhang, Zhi-Gang; Chen, Ya-Ping

    2015-01-01

    Ovarian cancer, the most lethal gynecological cancer, related closely to tumor stage. High-grade ovarian cancer always results in a late diagnose and high recurrence, which reduce survival within five years. Until recently, curable therapy is still under research and anti-angiogenesis proves a promising way. Tumor-derived exosomes are essential in tumor migration and metastases such as angiogenesis is enhanced by exosomes. In our study, we have made comparison between high-grade and unlikely high-grade serous ovarian cancer cells on exosomal function of endothelial cells proliferation, migration and tube formation. Exosomes derived from high-grade ovarian cancer have a profound impact on angiogenesis with comparison to unlikely high-grade ovarian cancer. Proteomic profiles revealed some potential proteins involved in exosomal function of angiogenesis such as ATF2, MTA1, ROCK1/2 and so on. Therefore, exosomes plays an influential role in angiogenesis in ovarian serous cancer and also function more effectively in high-grade ovarian cancer cells.

  15. Endocrine Therapy of Breast Cancer

    DTIC Science & Technology

    2009-06-01

    obtained breast specimens from breast cancer patients treated with endocrine therapy (or not, i.e., surgery and radiation only in selected...motility in vitro (Hiscox et al., 2006). In models of lung cancer and CML, Dasatinib can reduce AKT activity and expression of the prosurvival protein...measured by terminal deoxynucleotidyl transferse-mediated dUTP nick-end labeling (TUNEL) staining (Wedam et al., 2006). In an in vitro model of lung

  16. Endocrine Therapy of Breast Cancer

    DTIC Science & Technology

    2005-06-01

    breast cancers is whether an aromatase inhibitor, e.g., letrozole (LET) or TAM should be given as first line endocrine therapy . Unfortunately...response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies , e.g., -40% of tumors...effective treatment for hormone receptor positive invasive breast cancer. Such therapy includes antiestrogens (tamoxifen, fulvestrant ) and aromatase

  17. BILATERAL BREAST CANCER: DIAGNOSIS AND PROGNOSIS.

    PubMed

    Ursaru, Manuela; Jari, Irma; Gheorghe, Liliana; Naum, A G; Scripcariu, V; Negru, D

    2016-01-01

    To assess bilateral breast cancer patients, initially diagnosed with stage II unilateral breast cancer. 113 patients with stage 0-II breast cancer diagnosed between 1983 and 2011 were assessed. Of these, 8 patients had bilateral breast cancer: 7 patients with metachronous bilateral breast cancer and 1 patient with synchronous breast cancer. Breast ultrasound, mammography, computed tomography and magnetic resonance imaging were used to diagnose recurrence, loco regional and distant metastasis. Age at diagnosis ranged from 37 to 59 years, with a maximum age incidence in the 4th decade (age between: 31-40 years). The average time interval between the two breast cancers was 8.125 years. The most common histological type was invasive ductal carcinoma. All eight patients with bilateral breast cancer had at least one type of recurrence/metastasis, mostly in the liver, and statistically the pleuropulmonary and liver metastases were the most frequent causes of death. Patients in the 4th decade diagnosed with unilateral breast cancer are at risk of developing bilateral breast cancer. In metachronous breast cancer, the time interval between the detection of the second breast cancer and death is directly proportional to the time interval between the two breast cancers. TASTASES, DEATH.

  18. [Radiotherapy of breast cancer].

    PubMed

    Hennequin, C; Barillot, I; Azria, D; Belkacémi, Y; Bollet, M; Chauvet, B; Cowen, D; Cutuli, B; Fourquet, A; Hannoun-Lévi, J M; Leblanc, M; Mahé, M A

    2016-09-01

    In breast cancer, radiotherapy is an essential component of the treatment. After conservative surgery for an infiltrating carcinoma, radiotherapy must be systematically performed, regardless of the characteristics of the disease, because it decreases the rate of local recurrence and by this way, specific mortality. Partial breast irradiation could not be proposed routinely but only in very selected and informed patients. For ductal carcinoma in situ, adjuvant radiotherapy must be also systematically performed after lumpectomy. After mastectomy, chest wall irradiation is required for pT3-T4 tumours and if there is an axillary nodal involvement, whatever the number of involved lymph nodes. After neo-adjuvant chemotherapy and mastectomy, in case of pN0 disease, chest wall irradiation is recommended if there is a clinically or radiologically T3-T4 or node positive disease before chemotherapy. Axillary irradiation is recommended only if there is no axillary surgical dissection and a positive sentinel lymph node. Supra and infra-clavicular irradiation is advised in case of positive axillary nodes. Internal mammary irradiation must be discussed case by case, according to the benefit/risk ratio (cardiac toxicity). Dose to the chest wall or the breast must be between 45-50Gy with a conventional fractionation. A boost dose over the tumour bed is required if the patient is younger than 60 years old. Hypofractionation (42.5 Gy in 16 fractions, or 41.6 Gy en 13 or 40 Gy en 15) is possible after tumorectomy and if a nodal irradiation is not mandatory. Delineation of the breast, the chest wall and the nodal areas are based on clinical and radiological evaluations. 3D-conformal irradiation is the recommended technique, intensity-modulated radiotherapy must be proposed only in case of specific clinical situations. Respiratory gating could be useful to decrease the cardiac dose. Concomitant administration of chemotherapy in unadvised, but hormonal treatment could be start with

  19. Breast cancer: origins and evolution.

    PubMed

    Polyak, Kornelia

    2007-11-01

    Breast cancer is not a single disease, but rather is composed of distinct subtypes associated with different clinical outcomes. Understanding this heterogeneity is key for the development of targeted cancer-preventative and -therapeutic interventions. Current models explaining inter- and intratumoral diversity are the cancer stem cell and the clonal evolution hypotheses. Although tumor initiation and progression are predominantly driven by acquired genetic alterations, recent data implicate a role for microenvironmental and epigenetic changes as well. Comprehensive unbiased studies of tumors and patient populations have significantly advanced our molecular understanding of breast cancer, but translating these findings into clinical practice remains a challenge.

  20. Cigarette smoking and breast cancer.

    PubMed

    Baron, J A; Newcomb, P A; Longnecker, M P; Mittendorf, R; Storer, B E; Clapp, R W; Bogdan, G; Yuen, J

    1996-05-01

    A priori hypotheses suggest that cigarette smoking could either increase or decrease breast cancer incidence. To clarify these competing hypotheses, we used data from a very large population-based breast cancer case-control study to investigate the impact of smoking on breast cancer risk. Breast cancer patients less than 75 years old were identified from statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire; controls were randomly selected from driver's license lists (age less than 65) or lists of Medicare beneficiaries (age 65-74). Information on reproductive history, medical history, and personal habits including cigarette smoking was obtained by telephone interview. A total of 6,888 cases and 9,529 controls were interviewed. There was virtually no relationship between current smoking and breast cancer risk (multivariate odds ratio, 1.00; 95% confidence interval, 0.92-1.09), and former smokers had a barely increased risk (odds ratio, 1.10; 95% confidence interval, 1.01-1.19). Similar results were observed among both premenopausal and postmenopausal women. There was no suggestion that heavy or long-term smoking increased or decreased risk, nor were there indications that women who began smoking at an early age were at increased risk, as has been hypothesized. The results of this large population-based study indicate that smoking does not influence the risk of breast cancer, even among heavy smokers who began smoking at an early age.

  1. BREAST CANCER, DERMATOFIBROMAS AND ARSENIC

    PubMed Central

    Dantzig, Paul I

    2009-01-01

    Background: Dermatofibromas are common benign tumors in women, and breast cancer is the most common malignancy in women. The aim of this study is to determine if there is any relationship between the two conditions. Materials and Methods: Five patients with dermatofibromas and 10 control patients (two groups) had their skin biopsies measured for arsenic by inductively coupled mass spectrometry. Fifty randomly selected patients with breast cancer and 50 control patients were examined for the presence of dermatofibromas. Results: The dermatofibromas were found to have an arsenic concentration of 0.171 micrograms/gram, compared with 0.06 and 0.07 micrograms/gram of the two control groups. Forty-three out of 50 patients with breast cancer had dermatofibromas and 32/50 patients with breast cancer had multiple dermatofibromas, compared to 10/50 control patients with dermatofibromas and only 1/50 with multiple dermatofibromas. Conclusions: Arsenic is important in the development of dermatofibromas and dermatofibromas represent a reservoir and important sign of chronic arsenic exposure. Dermatofibromas represent an important sign for women at risk for breast cancer, and arsenic may represent the cause of the majority of cases of breast cancer. PMID:20049264

  2. Danish Breast Cancer Cooperative Group

    PubMed Central

    Christiansen, Peer; Ejlertsen, Bent; Jensen, Maj-Britt; Mouridsen, Henning

    2016-01-01

    Aim of database Danish Breast Cancer Cooperative Group (DBCG), with an associated database, was introduced as a nationwide multidisciplinary group in 1977 with the ultimate aim to improve the prognosis in breast cancer. Since then, the database has registered women diagnosed with primary invasive nonmetastatic breast cancer. The data reported from the departments to the database included details of the characteristics of the primary tumor, of surgery, radiotherapy, and systemic therapies, and of follow-up reported on specific forms from the departments in question. Descriptive data From 1977 through 2014, ~110,000 patients are registered in the nationwide, clinical database. The completeness has gradually improved to more than 95%. DBCG has continuously prepared evidence-based guidelines on diagnosis and treatment of breast cancer and conducted quality control studies to ascertain the degree of adherence to the guidelines in the different departments. Conclusion Utilizing data from the DBCG database, a long array of high-quality DBCG studies of various designs and scope, nationwide or in international collaboration, have contributed to the current updating of the guidelines, and have been an instrumental resource in the improvement of management and prognosis of breast cancer in Denmark. Thus, since the establishment of DBCG, the prognosis in breast cancer has continuously improved with a decrease in 5-year mortality from ~37% to 15%. PMID:27822082

  3. Urinary rubidium in breast cancers.

    PubMed

    Su, Yi; Chen, Li-Juan; He, Jian-Rong; Yuan, Xue-Jiao; Cen, Yu-Ling; Su, Feng-Xi; Tang, Lu-Ying; Zhang, Ai-Hua; Chen, Wei-Qing; Lin, Ying; Wang, Shen-Ming; Ren, Ze-Fang

    2011-11-20

    Rubidium is a putative anticancer agent, but no studies have been performed on the association of rubidium levels in biospecimen with breast cancer risk and the potential as a biomarker of the risk assessment. Survey data and urine specimens were collected from 240 women with incident invasive breast cancer before their treatments and 246 age-matched female controls between October 2009 and July 2010. Urinary concentrations of rubidium were determined by inductively coupled plasma mass spectrometry. Creatinine-adjusted levels [median (25th, 75th) ug/g] of rubidium in cases [2253.01(1606.81, 3110.46)] were significantly lower than that in the controls [2921.85 (2367.94, 4142.04)]. After adjustment for potential risk factors of breast cancer, women in the second and highest tertile decreased risk of breast cancer in a dose-dependent manner as compared with those in the lowest tertile [ORs and 95% CIs were 0.45 (0.27-0.73) and 0.22 (0.13-0.38), respectively]. The area under the receive-operating-characteristic curve for urinary rubidium level was 0.697 (95% CI: 0.650-0.743). The urinary levels of rubidium were significantly and inversely associated with risk of breast cancer and had potential to be a biomarker for breast cancer risk assessment. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Iodide transport and breast cancer.

    PubMed

    Poole, Vikki L; McCabe, Christopher J

    2015-10-01

    Breast cancer is the second most common cancer worldwide and the leading cause of cancer death in women, with incidence rates that continue to rise. The heterogeneity of the disease makes breast cancer exceptionally difficult to treat, particularly for those patients with triple-negative disease. To address the therapeutic complexity of these tumours, new strategies for diagnosis and treatment are urgently required. The ability of lactating and malignant breast cells to uptake and transport iodide has led to the hypothesis that radioiodide therapy could be a potentially viable treatment for many breast cancer patients. Understanding how iodide is transported, and the factors regulating the expression and function of the proteins responsible for iodide transport, is critical for translating this hypothesis into reality. This review covers the three known iodide transporters - the sodium iodide symporter, pendrin and the sodium-coupled monocarboxylate transporter - and their role in iodide transport in breast cells, along with efforts to manipulate them to increase the potential for radioiodide therapy as a treatment for breast cancer.

  5. Genetically Engineered Mice as Experimental Tools to Dissect the Critical Events in Breast Cancer

    PubMed Central

    Menezes, Mitchell E.; Das, Swadesh K.; Emdad, Luni; Windle, Jolene J.; Wang, Xiang-Yang; Sarkar, Devanand; Fisher, Paul B.

    2015-01-01

    Elucidating the mechanism of pathogenesis of breast cancer has greatly benefited from breakthrough advances in both genetically engineered mouse (GEM) models and xenograft transplantation technologies. The vast array of breast cancer mouse models currently available is testimony to the complexity of mammary tumorigenesis and attempts by investigators to accurately portray the heterogeneity and intricacies of this disease. Distinct molecular changes that drive various aspects of tumorigenesis, such as alterations in tumor cell proliferation and apoptosis, invasion and metastasis, angiogenesis, and drug resistance have been evaluated using the currently available GEM breast cancer models. GEM breast cancer models are also being exploited to evaluate and validate the efficacy of novel therapeutics, vaccines, and imaging modalities for potential use in the clinic. This review provides a synopsis of the various GEM models that are expanding our knowledge of the nuances of breast cancer development and progression and can be instrumental in the development of novel prevention and therapeutic approaches for this disease. PMID:24889535

  6. Zerumbone inhibits tumor angiogenesis via NF-κB in gastric cancer.

    PubMed

    Tsuboi, Ken; Matsuo, Yoichi; Shamoto, Tomoya; Shibata, Takahiro; Koide, Shuji; Morimoto, Mamoru; Guha, Sushovan; Sung, Bokyung; Aggarwal, Bharat B; Takahashi, Hiroki; Takeyama, Hiromitsu

    2014-01-01

    Zerumbone derived from a subtropical ginger, Zingiber zerumbet Smith, was previously reported to have antitumor growth and anti-inflammatory properties in some types of cancer. However, the effects of zerumbone against cancer angiogenesis have not been fully elucidated. In this study, we clarified the role of zerumbone in gastric cancer angiogenesis. We examined the expression of vascular endothelial growth factor (VEGF) in gastric cancer cell lines both in the basal state and following zerumbone treatment by real-time RT-PCR and enzyme-linked immunosorbent assay (ELISA). Changes in gastric cancer cell proliferation in response to zerumbone treatment were measured by WST-1 assay. Additionally, the effects of zerumbone on NF-κB activity were examined in AGS cells. Finally, the effects of zerumbone on angiogenesis in AGS cells were measured by in vitro angiogenesis assay in which human umbilical vein endothelial cells (HUVECs) and fibroblasts were cocultured with AGS cells. Among the 6 gastric cancer cell lines tested, AGS cells exhibited the highest expression of VEGF. Cell proliferation, VEGF expression and NF-κB activity in AGS cells were all significantly inhibited by zerumbone. Moreover, the tube formation area of HUVECs was increased by coculture with AGS cells, and this effect was inhibited by zerumbone. Both VEGF expression and NF-κB activity in AGS cells were reduced by treatment with zerumbone, thereby inhibiting angiogenesis. Thus, zerumbone may become a new anti-angiogenic and antitumor drug in the treatment of gastric cancer.

  7. Bradykinin promotes vascular endothelial growth factor expression and increases angiogenesis in human prostate cancer cells.

    PubMed

    Yu, Hsin-Shan; Wang, Shih-Wei; Chang, An-Chen; Tai, Huai-Ching; Yeh, Hung-I; Lin, Yu-Min; Tang, Chih-Hsin

    2014-01-15

    Prostate cancer is the most commonly diagnosed malignancy in men and shows a tendency for metastasis to distant organs. Angiogenesis is required for metastasis. Bradykinin (BK) is an inflammatory mediator involved in tumor growth and metastasis, but its role in vascular endothelial growth factor (VEGF) expression and angiogenesis in human prostate cancer remains unknown. The aim of this study was to examine whether BK promotes prostate cancer angiogenesis via VEGF expression. We found that exogenous BK increased VEGF expression in prostate cancer cells and further promoted tube formation in endothelial progenitor cells and human umbilical vein endothelial cells. Pretreatment of prostate cancer with B2 receptor antagonist or small interfering RNA (siRNA) reduced BK-mediated VEGF production. The Akt and mammalian target of rapamycin (mTOR) pathways were activated after BK treatment, and BK-induced VEGF expression was abolished by the specific inhibitor and siRNA of the Akt and mTOR cascades. BK also promoted nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) activity. Importantly, BK knockdown reduced VEGF expression and abolished prostate cancer cell conditional medium-mediated angiogenesis. Taken together, these results indicate that BK operates through the B2 receptor, Akt, and mTOR, which in turn activate NF-κB and AP-1, activating VEGF expression and contributing to angiogenesis in human prostate cancer cells.

  8. Natural Products for Chemoprevention of Breast Cancer

    PubMed Central

    Ko, Eun-Yi; Moon, Aree

    2015-01-01

    Breast cancer is the primary cause of cancer death in women. Although current therapies have shown some promise against breast cancer, there is still no effective cure for the majority of patients in the advanced stages of breast cancer. Development of effective agents to slow, reduce, or reverse the incidence of breast cancer in high-risk women is necessary. Chemoprevention of breast cancer by natural products is advantageous, as these compounds have few side effects and low toxicity compared to synthetic compounds. In the present review, we summarize natural products which exert chemopreventive activities against breast cancer, such as curcumin, sauchinone, lycopene, denbinobin, genipin, capsaicin, and ursolic acid. This review examines the current knowledge about natural compounds and their mechanisms that underlie breast cancer chemopreventive activity both in vitro and in vivo. The present review may provide information on the use of these compounds for the prevention of breast cancer. PMID:26734584

  9. Stroma Cells in Tumor Microenvironment and Breast Cancer

    PubMed Central

    Mao, Yan; Keller, Evan T.; Garfield, David H.; Shen, Kunwei; Wang, Jianhua

    2015-01-01

    Cancer is a systemic disease, encompassing multiple components of both tumor cells themselves and host stromal cells. It is now clear that stromal cells in the tumor microenvironment play an important role in cancer development. Molecular events through which reactive stromal cells affect cancer cells can be defined so that biomarkers and therapeutic targets can be identified. Cancer-associated fibroblasts (CAFs) make up the bulk of cancer stroma and affect the tumor microenvironment such that they promote cancer initiation, angiogenesis, invasion and metastasis. In breast cancer, CAFs not only promote tumor progression, but also induce therapeutic resistances. Accordingly, targeting CAFs provides a novel way to control tumors with therapeutic resistances. This review summarizes the current understanding of tumor stroma in breast cancer with a particular emphasis on the role of CAFs and the therapeutic implications of CAFs. The effects of other stromal components such as endothelial cells, macrophages and adipocytes in breast cancer are also discussed. Finally, we describe the biologic markers to sort patients into a specific and confirmed subtype for personalized treatment. PMID:23114846

  10. Environmental exposures, breast development and cancer risk: Through the looking glass of breast cancer prevention.

    PubMed

    Forman, Michele R; Winn, Deborah M; Collman, Gwen W; Rizzo, Jeanne; Birnbaum, Linda S

    2015-07-01

    This review summarizes the report entitled: Breast Cancer and the Environment: Prioritizing Prevention, highlights research gaps and the importance of focusing on early life exposures for breast development and breast cancer risk. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Environmental pollutants and breast cancer.

    PubMed Central

    Brody, Julia Green; Rudel, Ruthann A

    2003-01-01

    Breast cancer is the most common cancer in women and the leading cause of cancer death among women 35-54 years of age. Rising incidence, increased risk among migrants to higher risk regions, and poor prediction of individual risk have prompted a search for additional modifiable factors. Risk factors for breast cancer include reproductive characteristics associated with estrogen and other hormones, pharmaceutical hormones, and activities such as alcohol use and lack of exercise that affect hormone levels. As a result, investigation of hormonally active compounds in commercial products and pollution is a priority. Compounds that cause mammary tumors in animals are additional priorities. Animal models provide insight into possible mechanisms for effects of environmental pollutants on breast cancer and identify chemical exposures to target in epidemiologic studies. Although few epidemiologic studies have been conducted for chemical exposures, occupational studies show associations between breast cancer and exposure to certain organic solvents and polycyclic aromatic hydrocarbons (PAHs). Population-based studies have been limited to a few organochlorine compounds and PAHs and have been mostly negative. A variety of challenges in studies of breast cancer and the environment may have contributed to negative findings. Lack of exposure assessment tools and few hypothesis-generating toxicologic studies limit the scope of epidemiologic studies. Issues of timing with respect to latency and periods of breast vulnerability, and individual differences in susceptibility pose other challenges. Substantial work is needed in exposure assessment, toxicology, and susceptibility before we can expect a pay-off from large epidemiologic studies of breast cancer and environment. PMID:12826474

  12. A novel assay to assess the effectiveness of antiangiogenic drugs in human breast cancer.

    USDA-ARS?s Scientific Manuscript database

    Many cytotoxic drugs maintain antiangiogenic properties, but there are no human, tumor-based assays to evaluate their antiangiogenic potential. We used a fibrin-thrombin clot-based angiogenesis model to evaluate the angiogenic response of human breast cancer to various cytotoxic agents commonly used...

  13. Targeting breast cancer-initiating/stem cells with melanoma differentiation-associated gene-7/interleukin-24

    PubMed Central

    Bhutia, Sujit K.; Das, Swadesh K.; Azab, Belal; Menezes, Mitchell E.; Dent, Paul; Wang, Xiang-Yang; Sarkar, Devanand; Fisher, Paul B.

    2015-01-01

    Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) displays a broad range of antitumor properties including cancer-specific induction of apoptosis, inhibition of tumor angiogenesis and modulation of antitumor immune responses. In our study, we elucidated the role of MDA-7/IL-24 in inhibiting growth of breast cancer-initiating/stem cells. Ad.mda-7 infection decreased proliferation of breast cancer-initiating/stem cells without affecting normal breast stem cells. Ad.mda-7 induced apoptosis and endoplasmic reticulum stress in breast cancer-initiating/stem cells similar to unsorted breast cancer cells and inhibited the self-renewal property of breast cancer-initiating/stem cells by suppressing Wnt/β-catenin signaling. Prevention of inhibition of Wnt signaling by LiCl increased cell survival upon Ad.mda-7 treatment, suggesting that Wnt signaling inhibition might play a key role in MDA-7/IL-24-mediated death of breast cancer-initiating/stem cells. In a nude mouse subcutaneous xenograft model, Ad.mda-7 injection profoundly inhibited growth of tumors generated from breast cancer-initiating/stem cells and also exerted a potent “bystander” activity inhibiting growth of distant uninjected tumors. Further studies revealed that tumor growth inhibition by Ad.mda-7 was associated with a decrease in proliferation and angiogenesis, two intrinsic features of MDA-7/IL-24, and a reduction in vivo in the percentage of breast cancer-initiating/stem cells. Our findings demonstrate that MDA-7/IL-24 is not only nontoxic to normal cells and normal stem cells but also can kill both unsorted cancer cells and enriched populations of cancer-initiating/stem cells, providing further documentation that MDA-7/IL-24 might be a safe and effective way to eradicate cancers and also potentially establish disease-free survival. PMID:23720015

  14. COX-2 – A Novel Target for Reducing Tumor Angiogenesis and Metastasis | Center for Cancer Research

    Cancer.gov

    Angiogenesis is essential for tumor growth and metastasis, by supplying a steady stream of nutrients, removing waste, and providing tumor cells access to other sites in the body. The vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) play a key role in tumor-mediated angiogenesis, and this pathway is the target of monoclonal antibodies and tyrosine kinase inhibitors (TKIs) that have been approved to treat patients with cancer. Unfortunately, tumors can use alternative angiogenesis mechanisms to escape VEGF pathway blockade, but these alternate pathways are not well understood. Brad St. Croix, Ph.D., of CCR’s Mouse Cancer Genetics Program, along with Lihong Xu, Ph.D., a Postdoctoral Fellow in the St. Croix laboratory, and colleagues set out to identify VEGF-independent mediators of tumor angiogenesis.

  15. New Immunotherapy Strategies in Breast Cancer

    PubMed Central

    Yu, Lin-Yu; Tang, Jie; Zhang, Cong-Min; Zeng, Wen-Jing; Yan, Han; Li, Mu-Peng; Chen, Xiao-Ping

    2017-01-01

    Breast cancer is the most commonly diagnosed cancer among women. Therapeutic treatments for breast cancer generally include surgery, chemotherapy, radiotherapy, endocrinotherapy and molecular targeted therapy. With the development of molecular biology, immunology and pharmacogenomics, immunotherapy becomes a promising new field in breast cancer therapies. In this review, we discussed recent progress in breast cancer immunotherapy, including cancer vaccines, bispecific antibodies, and immune checkpoint inhibitors. Several additional immunotherapy modalities in early stages of development are also highlighted. It is believed that these new immunotherapeutic strategies will ultimately change the current status of breast cancer therapies. PMID:28085094

  16. New Immunotherapy Strategies in Breast Cancer.

    PubMed

    Yu, Lin-Yu; Tang, Jie; Zhang, Cong-Min; Zeng, Wen-Jing; Yan, Han; Li, Mu-Peng; Chen, Xiao-Ping

    2017-01-12

    Breast cancer is the most commonly diagnosed cancer among women. Therapeutic treatments for breast cancer generally include surgery, chemotherapy, radiotherapy, endocrinotherapy and molecular targeted therapy. With the development of molecular biology, immunology and pharmacogenomics, immunotherapy becomes a promising new field in breast cancer therapies. In this review, we discussed recent progress in breast cancer immunotherapy, including cancer vaccines, bispecific antibodies, and immune checkpoint inhibitors. Several additional immunotherapy modalities in early stages of development are also highlighted. It is believed that these new immunotherapeutic strategies will ultimately change the current status of breast cancer therapies.

  17. Breast Cancer Surgery

    MedlinePlus

    ... and nipple-sparing mastectomy If you are having breast reconstruction at the same time as a mastectomy, the ... a few surgeons (and if you are getting breast reconstruction, a few plastic surgeons). Choose one who does ...

  18. VEGF and colon cancer growth beyond angiogenesis: does VEGF directly mediate colon cancer growth via a non-angiogenic mechanism?

    PubMed

    Ahluwalia, Amrita; Jones, Michael K; Matysiak-Budnik, Tamara; Tarnawski, Andrzej S

    2014-01-01

    In this article we review the role of vascular endothelial growth factor (VEGF) in colon cancer growth and the underlying mechanisms. Angiogenesis, the growth of new capillary blood vessels in the body, is critical for tissue injury healing and cancer growth. In 1971, Judah Folkman proposed the concept that tumor growth beyond 2 mm is critically dependent on angiogenesis. Tumors including colon cancers release angiogenic growth factors that stimulate blood vessels to grow into the tumors thus providing oxygen and nutrients that enable exponential growth. VEGF is the most potent angiogenic growth factor. Several studies have highlighted the role of VEGF in colon cancer, specifically in the stimulation of angiogenesis. This role of VEGF is strongly supported by studies showing that inhibition of VEGF using the blocking antibody, bevacizumab, results in decreased angiogenesis and abrogation of cancer growth. In the United States, bevacizumab in combination with chemotherapy is FDA approved for the treatment of metastatic colon cancer. However, the source of VEGF in colon cancer tissue, the mechanisms of VEGF generation in colon cancer cells and the molecular pathways involved in VEGF mediated angiogenesis in colon cancer are not fully known. The possibility that VEGF directly stimulates cancer cell growth in an autocrine manner has not been explored in depth.

  19. Anti-Vascular Endothelial Growth Factor Therapy in Breast Cancer

    PubMed Central

    Kristensen, Tina Bøgelund; Knutsson, Malin L. T.; Wehland, Markus; Laursen, Britt Elmedal; Grimm, Daniela; Warnke, Elisabeth; Magnusson, Nils E.

    2014-01-01

    Neo-angiogenesis is a critical process for tumor growth and invasion and has become a promising target in cancer therapy. This manuscript reviews three currently relevant anti-angiogenic agents targeting the vascular endothelial growth factor system: bevacizumab, ramucirumab and sorafenib. The efficacy of anti-angiogenic drugs in adjuvant therapy or as neo-adjuvant treatment has been estimated in clinical trials of advanced breast cancer. To date, the overall observed clinical improvements are unconvincing, and further research is required to demonstrate the efficacy of anti-angiogenic drugs in breast cancer treatments. The outcomes of anti-angiogenic therapy have been highly variable in terms of tumor response. New methods are needed to identify patients who will benefit from this regimen. The development of biomarkers and molecular profiling are relevant research areas that may strengthen the ability to focus anti-angiogenic therapy towards suitable patients, thereby increase the cost-effectiveness, currently estimated to be inadequate. PMID:25514409

  20. Genomic profiling of breast cancers.

    PubMed

    Curtis, Christina

    2015-02-01

    To describe recent advances in the application of advanced genomic technologies towards the identification of biomarkers of prognosis and treatment response in breast cancer. Advances in high-throughput genomic profiling such as massively parallel sequencing have enabled researchers to catalogue the spectrum of somatic alterations in breast cancers. These tools also hold promise for precision medicine through accurate patient prognostication, stratification, and the dynamic monitoring of treatment response. For example, recent efforts have defined robust molecular subgroups of breast cancer and novel subtype-specific oncogenes. In addition, previously unappreciated activating mutations in human epidermal growth factor receptor 2 have been reported, suggesting new therapeutic opportunities. Genomic profiling of cell-free tumor DNA and circulating tumor cells has been used to monitor disease burden and the emergence of resistance, and such 'liquid biopsy' approaches may facilitate the early, noninvasive detection of aggressive disease. Finally, single-cell genomics is coming of age and will contribute to an understanding of breast cancer evolutionary dynamics. Here, we highlight recent studies that employ high-throughput genomic technologies in an effort to elucidate breast cancer biology, discover new therapeutic targets, improve prognostication and stratification, and discuss the implications for precision cancer medicine.

  1. AR Signaling in Breast Cancer

    PubMed Central

    Rahim, Bilal; O’Regan, Ruth

    2017-01-01

    Androgen receptor (AR, a member of the steroid hormone receptor family) status has become increasingly important as both a prognostic marker and potential therapeutic target in breast cancer. AR is expressed in up to 90% of estrogen receptor (ER) positive breast cancer, and to a lesser degree, human epidermal growth factor 2 (HER2) amplified tumors. In the former, AR signaling has been correlated with a better prognosis given its inhibitory activity in estrogen dependent disease, though conversely has also been shown to increase resistance to anti-estrogen therapies such as tamoxifen. AR blockade can mitigate this resistance, and thus serves as a potential target in ER-positive breast cancer. In HER2 amplified breast cancer, studies are somewhat conflicting, though most show either no effect or are associated with poorer survival. Much of the available data on AR signaling is in triple-negative breast cancer (TNBC), which is an aggressive disease with inferior outcomes comparative to other breast cancer subtypes. At present, there are no approved targeted therapies in TNBC, making study of the AR signaling pathway compelling. Gene expression profiling studies have also identified a luminal androgen receptor (LAR) subtype that is dependent on AR signaling in TNBC. Regardless, there seems to be an association between AR expression and improved outcomes in TNBC. Despite lower pathologic complete response (pCR) rates with neoadjuvant therapy, patients with AR-expressing TNBC have been shown to have a better prognosis than those that are AR-negative. Clinical studies targeting AR have shown somewhat promising results. In this paper we review the literature on the biology of AR in breast cancer and its prognostic and predictive roles. We also present our thoughts on therapeutic strategies. PMID:28245550

  2. AR Signaling in Breast Cancer.

    PubMed

    Rahim, Bilal; O'Regan, Ruth

    2017-02-24

    Androgen receptor (AR, a member of the steroid hormone receptor family) status has become increasingly important as both a prognostic marker and potential therapeutic target in breast cancer. AR is expressed in up to 90% of estrogen receptor (ER) positive breast cancer, and to a lesser degree, human epidermal growth factor 2 (HER2) amplified tumors. In the former, AR signaling has been correlated with a better prognosis given its inhibitory activity in estrogen dependent disease, though conversely has also been shown to increase resistance to anti-estrogen therapies such as tamoxifen. AR blockade can mitigate this resistance, and thus serves as a potential target in ER-positive breast cancer. In HER2 amplified breast cancer, studies are somewhat conflicting, though most show either no effect or are associated with poorer survival. Much of the available data on AR signaling is in triple-negative breast cancer (TNBC), which is an aggressive disease with inferior outcomes comparative to other breast cancer subtypes. At present, there are no approved targeted therapies in TNBC, making study of the AR signaling pathway compelling. Gene expression profiling studies have also identified a luminal androgen receptor (LAR) subtype that is dependent on AR signaling in TNBC. Regardless, there seems to be an association between AR expression and improved outcomes in TNBC. Despite lower pathologic complete response (pCR) rates with neoadjuvant therapy, patients with AR-expressing TNBC have been shown to have a better prognosis than those that are AR-negative. Clinical studies targeting AR have shown somewhat promising results. In this paper we review the literature on the biology of AR in breast cancer and its prognostic and predictive roles. We also present our thoughts on therapeutic strategies.

  3. Breast Cancer Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing breast cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  4. Screening for Breast Cancer: Detection and Diagnosis

    MedlinePlus

    ... page please turn JavaScript on. Feature: Screening For Breast Cancer Detection and Diagnosis Past Issues / Summer 2014 Table ... States Preventive Services Task Force updated recommendations on breast cancer screening, suggesting that women ages 50 to 74 ...

  5. Screening for Breast Cancer: Staging and Treatment

    MedlinePlus

    ... page please turn JavaScript on. Feature: Screening For Breast Cancer Staging and Treatment Past Issues / Summer 2014 Table of Contents Staging The extent (stage) of breast cancer needs to be determined to help choose the ...

  6. Breast Cancer and Estrogen-Alone Update

    MedlinePlus

    ... Current Issue Past Issues Research News From NIH Breast Cancer and Estrogen-Alone Update Past Issues / Summer 2006 ... hormone therapy does not increase the risk of breast cancer in postmenopausal women, according to an updated analysis ...

  7. Breast Cancer and the Environment Research Program

    Cancer.gov

    The Breast Cancer and the Environment Research Program supports a multidisciplinary network of scientists, clinicians, and community partners to examine the effects of environmental exposures that may predispose a woman to breast cancer throughout her life.

  8. What Is Breast Cancer in Men?

    MedlinePlus

    ... or spread (metastasize) to distant areas of the body. Cells in nearly any part of the body can ... if any lobules. Like all cells of the body, a man's breast duct cells can undergo cancerous changes. But breast cancer is ...

  9. Loneliness May Sabotage Breast Cancer Survival: Study

    MedlinePlus

    ... gov/news/fullstory_162498.html Loneliness May Sabotage Breast Cancer Survival: Study Weak social ties linked to higher ... 2016 (HealthDay News) -- Loneliness may impede long-term breast cancer survival, a new study suggests. In the years ...

  10. Hormone Therapy for Breast Cancer in Men

    MedlinePlus

    ... this is largely based on how well they work in women with breast cancer. Tamoxifen and toremifene (Fareston ® ) These anti-estrogen drugs work by temporarily blocking estrogen receptors on breast cancer ...

  11. Contralateral Breast Cancers: Independent Cancers or Metastases?

    PubMed

    Begg, Colin B; Ostrovnaya, Irina; Geyer, Felipe C; Papanastasiou, Anastasios D; Ng, Charlotte Ky; Sakr, Rita; Bernstein, Jonine L; Burke, Kathleen A; King, Tari A; Piscuoglio, Salvatore; Mauguen, Audrey; Orlow, Irene; Weigelt, Britta; Seshan, Venkatraman E; Morrow, Monica; Reis-Filho, Jorge S

    2017-09-16

    A cancer in the contralateral breast in a woman with a previous or synchronous breast cancer is typically considered to be an independent primary tumor. Emerging evidence suggests that in a small subset of these cases the second tumor represents a metastasis. We sought to investigate the issue using massively parallel sequencing targeting 254 genes recurrently mutated in breast cancer. We examined the tumor archives at Memorial Sloan Kettering Cancer Center for the period 1995-2006 to identify cases of contralateral breast cancer where surgery for both tumors was performed at the Center. We report results from 49 patients successfully analyzed by a targeted massively parallel sequencing assay. Somatic mutations and copy number alterations were defined by state-of-the-art algorithms. Clonal relatedness was evaluated by statistical tests specifically designed for this purpose. We found evidence that the tumors in contralateral breasts were clonally related in 3 cases (6%) on the basis of matching mutations at codons where somatic mutations are rare. Clinical data and the presence of similar patterns of gene copy number alterations were consistent with metastasis for all 3 cases. In 3 additional cases there was a solitary matching mutation at a common PIK3CA locus. The results suggest that a subset of contralateral breast cancers represent metastases rather than independent primary tumors. Massively parallel sequencing analysis can provide important evidence to clarify the diagnosis. However, given the inter-tumor mutational heterogeneity in breast cancer, sufficiently large gene panels need to be employed to define clonality convincingly in all cases. This article is protected by copyright. All rights reserved. © 2017 UICC.

  12. Veliparib, Cisplatin, and Vinorelbine Ditartrate in Treating Patients With Recurrent and/or Metastatic Breast Cancer

    ClinicalTrials.gov

    2017-02-27

    Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Hereditary Breast/Ovarian Cancer - BRCA1; Hereditary Breast/Ovarian Cancer - BRCA2; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer

  13. Alternative Dosing of Exemestane Before Surgery in Treating Postmenopausal Patients With Stage 0-II Estrogen Positive Breast Cancer

    ClinicalTrials.gov

    2017-02-17

    Estrogen Receptor Positive; Postmenopausal; Stage 0 Breast Cancer; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

  14. Fulvestrant and Palbociclib in Treating Older Patients With Hormone Responsive Breast Cancer That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-09-21

    Estrogen Receptor and/or Progesterone Receptor Positive; HER2/Neu Negative; 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

  15. Heavy Metal Exposure in Predicting Peripheral Neuropathy in Patients With Stage I-III Breast Cancer Undergoing Chemotherapy

    ClinicalTrials.gov

    2017-06-14

    Male Breast Cancer; Neurotoxicity; Peripheral Neuropathy; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  16. Minocycline Hydrochloride in Reducing Chemotherapy Induced Depression and Anxiety in Patients With Stage I-III Breast Cancer

    ClinicalTrials.gov

    2017-01-28

    Anxiety Disorder; Depression; 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

  17. Saracatinib in Treating Patients With Metastatic or Locally Advanced Breast Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2014-04-02

    Estrogen Receptor-negative Breast Cancer; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Recurrent Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  18. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Isolation of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Same long-term growth human mammary epithelial cells (HMEC), but after 3 weeks in concinuous culture. Note attempts to reform duct elements, but this time in two dimensions in a dish rather that in three demensions in tissue. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Robert Tichmond, NASA/Marshall Space Flight Center (MSFC).

  19. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Isolation of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Isolate of long-term growth human mammary epithelial cells (HMEC) from outgrowth of duct element; cells shown soon after isolation and early in culture in a dish. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Robert Tichmond, NASA/Marshall Space Flight Center (MSFC).

  20. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Isolation of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Outgrowth of cells from duct element in upper right corner cultured in a standard dish; most cells spontaneously die during early cell divisions, but a few will establish long-term growth. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Robert Tichmond, NASA/Marshall Space Flight Center (MSFC).

  1. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Isolation of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Outgrowth of cells from duct element in upper right corner cultured in a standard dish; most cells spontaneously die during early cell divisions, but a few will establish long-term growth. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Robert Tichmond, NASA/Marshall Space Flight Center (MSFC).

  2. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Isolation of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Same long-term growth human mammary epithelial cells (HMEC), but after 3 weeks in concinuous culture. Note attempts to reform duct elements, but this time in two dimensions in a dish rather that in three demensions in tissue. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Robert Tichmond, NASA/Marshall Space Flight Center (MSFC).

  3. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Isolation of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Isolate of long-term growth human mammary epithelial cells (HMEC) from outgrowth of duct element; cells shown soon after isolation and early in culture in a dish. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Robert Tichmond, NASA/Marshall Space Flight Center (MSFC).

  4. Bioluminescence Imaging of Angiogenesis in a Murine Orthotopic Pancreatic Cancer Model

    PubMed Central

    Chen, Monica; Mojadidi, Michelle; Hines, O. Joe; Reber, Howard A.; Eibl, Guido

    2010-01-01

    Purpose Angiogenesis is essential for physiological processes as well as for carcinogenesis. New approaches to cancer therapy include targeting angiogenesis. One target is VEGF-A and its receptor VEGFR2. In this study, we sought to investigate pancreatic cancer angiogenesis in a genetically modified VEGFR2-luc-KI mouse. Procedures Live in vivo bioluminescence imaging of angiogenesis was performed continuously until sacrifice in subcutaneous tumors as well as in orthotopically transplanted tumors. Tumor tissue was immunostained for CD-31 and VEGFR2. Results Peritumoral angiogenesis measured by light emission was detected beginning at week 3 following subcutaneous injection. In the orthotopic model, light emission began at day 4, which likely corresponds to wound healing, and continued throughout the experimental period during tumor growth. Peritumoral CD-31 vessel- and VEGFR2-staining were positive. Conclusions The VEGFR2-luc-KI mouse is a valuable tool to demonstrate tumor angiogenesis and seems to be suitable to evaluate anti-angiogenic approaches in pancreatic cancer. PMID:20376570

  5. The Epidemiology of Male Breast Cancer.

    PubMed

    Ferzoco, Raina M; Ruddy, Kathryn J

    2016-01-01

    Male breast cancer is a rare disease, accounting for only 1% of breast cancer diagnoses in the USA. The current literature suggests that genetic factors including BRCA2 mutations, family history, age, androgen/estrogen imbalance, and environmental exposures may predispose to male breast cancer. In this manuscript, we will review known and possible risk factors for male breast cancer, as well as describe the clinical patterns of the disease.

  6. Pro-Apoptotic Breast Cancer Nanotherapeutics

    DTIC Science & Technology

    2013-07-01

    basal-like breast cancer using a novel nanotechnology platform pioneered by my mentor Prof. Stupp. Our original plan was to combine nanoparticles ...Fellowship has supported my training in translational breast cancer research as part of an interdisciplinary team of scientists using nanotechnology to...basal-like breast cancer . 15. SUBJECT TERMS Nanotechnology ; Peptide Amphiphile; Drug Delivery; Breast Cancer ; Cell Death 16. SECURITY CLASSIFICATION OF

  7. p16 Modulates VEGF Expression via Its Interaction With HIF-1α in Breast Cancer Cells

    PubMed Central

    Zhang, Jun; Lu, Andrew; Li, Liyuan; Yue, Junming; Lu, Yi

    2010-01-01

    The degree of tumor progression (such as growth, angiogenesis, and metastasis) directly correlates with the expression of vascular endothelial growth factor (VEGF), but inversely correlates with the expression of tumor-suppressor gene p16, therefore we examined whether the restoration of p16 in breast cancer cells would modulate VEGF expression. Adenoviral-mediated p16 expression downregulated VEGF gene expression in breast cancer cells, and inhibited breast cancer cell-induced angiogenesis by a dorsal air sac model in mice. Moreover, p16 appears to form a complex with HIF-1α, the transcription factor for the VEGF gene promoter. Taken together, the binding between p16 and HIF-1α protein may alter HIF-1α’s ability to transactivate VEGF expression. PMID:20307196

  8. Multi-epitope Folate Receptor Alpha Peptide Vaccine, Sargramostim, and Cyclophosphamide in Treating Patients With Triple Negative Breast Cancer

    ClinicalTrials.gov

    2017-01-24

    Bilateral Breast Carcinoma; Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma; Unilateral Breast Carcinoma

  9. IL-17 promotes tumor angiogenesis through Stat3 pathway mediated upregulation of VEGF in gastric cancer.

    PubMed

    Wu, Xiaoqin; Yang, Tao; Liu, Xiang; Guo, Jia Nian; Xie, Tingting; Ding, Yuanwei; Lin, Manpeng; Yang, Hui

    2016-04-01

    Gastric cancer is the world's second most common malignancy and is a major threat to global health. IL-17, a CD4 T cell-derived mediator of angiogenesis, plays a major role in stimulating angiogenesis by regulating the production of a variety of proangiogenic factors, including the vascular endothelial growth factor (VEGF). The level of VEGF expression correlates with tumor progression and metastasis in gastric cancer tissues. Abnormal activation of signal transducer and activator of transcription 3 (Stat3) rendered the tumor cells highly angiogenic, which is manifested by an increased microvascular density (MVD) and considered it as a potential molecular marker for poor prognosis in gastric cancer angiogenesis. We determined that IL-17A-induced VEGF upregulation and neovascularization through a Stat3-mediated signaling pathway and hypothesized that blocking the Stat3 activation by using JSI-124, an inhibitor of phosphorylated Stat3, could significantly reduce the VEGF expression and can thus prevent angiogenesis. We showed an inhibition of angiogenesis and tumor progression when JSI-124 was treated with IL-17A in the cells and xenografts in an animal model and suggested that targeting the Stat pathway with JSI-124 could derive an effective therapeutic target for gastric cancers and could be a promising drug in gastric cancer treatment.

  10. Targeting Androgen Receptor in Breast Cancer: Enzalutamide as a Novel Breast Cancer Therapeutic

    DTIC Science & Technology

    2016-09-01

    Award Number: W81XWH-13-1-0091 TITLE: Targeting Androgen Receptor in Breast Cancer : Enzalutamide as a Novel Breast Cancer Therapeutic PRINCIPAL...2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting Androgen Receptor in Breast Cancer : Enzalutamide as a Novel Breast Cancer Therapeutic 5b...activity in breast cancer as a single agent and in combination with exemestane. Activity is seen in both triple negative AR+ BC and also ER+AR+ BC

  11. Targeting of CD151 in Breast Cancer and in Breast Cancer Stem Cells

    DTIC Science & Technology

    2007-04-01

    role in the progression of breast cancer . 15. SUBJECT TERMS CD151 protein, breast cancer progression, ErbB2 amplification, breast carcinoma invasion... malignancy in breast cancer and other types of cancer . Others had found that CD151 knockout mice show normal development, but deficiencies in wound...antagonists can disrupt mammary carcinoma functions. BODY: a. Establishing a mouse model for breast cancer - We attempted to cross our CD151 null

  12. Multicenter Breast Cancer Collaborative Registry

    PubMed Central

    Sherman, Simon; Shats, Oleg; Fleissner, Elizabeth; Bascom, George; Yiee, Kevin; Copur, Mehmet; Crow, Kate; Rooney, James; Mateen, Zubeena; Ketcham, Marsha A.; Feng, Jianmin; Sherman, Alexander; Gleason, Michael; Kinarsky, Leo; Silva-Lopez, Edibaldo; Edney, James; Reed, Elizabeth; Berger, Ann; Cowan, Kenneth

    2011-01-01

    The Breast Cancer Collaborative Registry (BCCR) is a multicenter web-based system that efficiently collects and manages a variety of data on breast cancer (BC) patients and BC survivors. This registry is designed as a multi-tier web application that utilizes Java Servlet/JSP technology and has an Oracle 11g database as a back-end. The BCCR questionnaire has accommodated standards accepted in breast cancer research and healthcare. By harmonizing the controlled vocabulary with the NCI Thesaurus (NCIt) or Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT), the BCCR provides a standardized approach to data collection and reporting. The BCCR has been recently certified by the National Cancer Institute’s Center for Biomedical Informatics and Information Technology (NCI CBIIT) as a cancer Biomedical Informatics Grid (caBIG®) Bronze Compatible product. The BCCR is aimed at facilitating rapid and uniform collection of critical information and biological samples to be used in developing diagnostic, prevention, treatment, and survivorship strategies against breast cancer. Currently, seven cancer institutions are participating in the BCCR that contains data on almost 900 subjects (BC patients and survivors, as well as individuals at high risk of getting BC). PMID:21918596

  13. Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer)

    ClinicalTrials.gov

    2017-03-30

    Breast Tumor; Breast Cancer; Cancer of the Breast; Estrogen Receptor- Negative Breast Cancer; HER2- Negative Breast Cancer; Progesterone Receptor- Negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer; Triple-negative Metastatic Breast Cancer; Metastatic Breast Cancer

  14. Breast Cancer and Posttraumatic Growth

    PubMed Central

    İnan, Figen Şengün; Üstün, Besti

    2014-01-01

    The current methods for early diagnosis and increased treatment options have improved survival rates in breast cancer. Breast cancer diagnosis effects individuals in physical, psychological and social dimensions either positively or negatively. In the literature, usually the negative effects encountered in the period after the diagnosis of breast cancer are mostly described, with limited data on the positive effects. Nevertheless, the identification of positive changes and defining its determinants is important in supporting and strengthening posttraumatic growth in this group. The objective of this review is to explain posttraumatic growth and its determinants in breast cancer during the post-treatment period in accordance with the relevant literature. In our evaluation, it was noticed that breast cancer survivors experience posttraumatic growth in the post-treatment period, but the literature is limited in explaining the nature of posttraumatic growth and its determinants. Both qualitative and quantitative research that will provide in-depth information on the subject, explaining culture-specific posttraumatic growth and related factors, are required. PMID:28331647

  15. MiR-122 targets VEGFC in bladder cancer to inhibit tumor growth and angiogenesis

    PubMed Central

    Wang, Yi; Xing, Qing-Fei; Liu, Xiao-Qiang; Guo, Zhan-Jun; Li, Chang-Ying; Sun, Guang

    2016-01-01

    Previous studies indicate that microRNA-122 (miR-122) is down-regulated in several cancer cells and regulates cell apoptosis, proliferation, metastasis, and tumor angiogenesis. However, the mount of miR-122 in bladder cancer and the pivotal molecular mechanisms of miR-122 used to regulate bladder carcinogenesis and angiogenesis remain to be clarified. Here, we reveal that miR-122 expression is down-regulated in human bladder cancer tissues and cell lines. MiR-122 represses vascular endothelial growth factor C (VEGFC) post-transcriptional expression by directly binding to its 3’-UTR. The protein kinase B (AKT) and mammalian target of rapamycin (mTOR), which are the most important downstream molecules of VEGFC, are also decreased in bladder cancer cell after miR-122 overexpression. Furthermore, miR-122 over-expression decreases bladder cancer cell migration, invasion, colony formation in vitro and slow bladder cancer growth and angiogenesis in vivo. Finally, miR-122 sensitizes bladder cancer cells to cisplatin-induced apoptosis. Taken together, these studies suggest that miR-122 serves as a tumor suppressor and down-regulating VEGFC expression, leading to the inhibition of bladder cancer growth and angiogenesis. PMID:27508026

  16. Prokineticin 2 (PROK2) is an important factor for angiogenesis in colorectal cancer.

    PubMed

    Kurebayashi, Hidetaka; Goi, Takanori; Shimada, Michiaki; Tagai, Noriyuki; Naruse, Takayuki; Nakazawa, Toshiyuki; Kimura, Youhei; Hirono, Yasuo; Yamaguchi, Akio

    2015-09-22

    The Prokineticin 2 (PROK2) is correlated with indispensable in maintaining the homeostasis of healthy human tissues. Herein, we examined the role of PROK2 in human colorectal cancer.After total RNA extraction from 6 colorectal cancer cell lines, we examined the expression of PROK2 mRNA. For investigating angiogenesis and tumor growth in mice, the PROK2 gene was transfected into colorectal cancer cell lines having low PROK2 mRNA expression. In addition, small interfering RNA (siRNA) was transfected into colorectal cancer cell lines having high PROK2 mRNA expression for investigation of angiogenesis and tumor growth in mice.From 6 colorectal cancer cell lines studied, PROK2 mRNA expression was increased in 3 cell lines. When the PROK2 gene was transfected into the colorectal cancer cell line with low PROK2 mRNA expression, angiogenesis and tumor growth in mice increased significantly compared to the cell line with the control vector.When PROK2 siRNA was transfected into colorectal cancer cell lines with high PROK2 mRNA expression, angiogenesis and tumor growth in mice were suppressed significantly compared to the cell line with siRNA (control).This is the first report of the association of PROK2 as an angiogenic growth factor in colorectal cancer.

  17. Vascular endothelial growth factor A (VEGF-A) mRNA expression levels decrease after menopause in normal breast tissue but not in breast cancer lesions

    PubMed Central

    Greb, R R; Maier, I; Wallwiener, D; Kiesel, L

    1999-01-01

    We hypothesized that the regulation of microvascular functions and angiogenesis in breast tissue, a well known target of ovarian steroid action, is dependent on the hormonal exposure of the breast. Relative expression levels of VEGF-A (vascular endothelial growth factor A), a putative key regulator of angiogenesis in breast cancer, were analysed in the tumour and the adjacent non-neoplastic breast tissue of 19 breast cancer patients by quantitative reverse transcriptase polymerase chain reaction. In non-neoplastic breast specimens the expression levels of all detected VEGF-A-isoforms (189, 165, 121) were significantly higher in premenopausal compared to post-menopausal women (P = 0.02) and were inversely correlated with the patient's age (P = 0.006). In contrast, in cancerous tissues menopausal status had no influence on VEGF-A-expression levels. Benign and malignant tissues exhibited a similar expression pattern of VEGF-A-isoforms relative to each other. Thus, the regulation of the vasculature in normal breast tissue, as opposed to breast cancer tissue, appears to be hormonally dependent. Endogenous and therapeutically used hormonal steroids might, therefore, cause clinically relevant changes of the angiogenic phenotype of the human breast. © 1999 Cancer Research Campaign PMID:10496346

  18. Internet Use and Breast Cancer Survivors

    ERIC Educational Resources Information Center

    Muhamad, Mazanah; Afshari, Mojgan; Mohamed, Nor Aini

    2011-01-01

    A survey was administered to 400 breast cancer survivors at hospitals and support group meetings in Peninsular Malaysia to explore their level of Internet use and factors related to the Internet use by breast cancer survivors. Findings of this study indicated that about 22.5% of breast cancer survivors used Internet to get information about breast…

  19. Do underarm cosmetics cause breast cancer?

    PubMed

    Gikas, Panagiotis D; Mansfield, Lucy; Mokbel, Kefah

    2004-01-01

    Although animal and laboratory studies suggest a possible link between certain chemicals used in underarm cosmetics and breast cancer development, there is no reliable evidence that underarm cosmetics use increases breast cancer risk in humans. This article reviews the evidence for and against the possible link between breast cancer and underarm cosmetics and highlights the need for further research to clarify this issue.

  20. Breast cancer in young women.

    PubMed

    Winchester, D P

    1996-04-01

    Breast cancer is an uncommon disease in women under the age of 40 years, reportedly accounting for 7.5% of reported cases. Delay in diagnosis is attributable to a clinically low index of suspicion, difficulty in examining dense and nodular breasts in younger women, and less frequently performed screening mammography. Genetic mutations should be suspected in women with breast cancer who are under the age of 30 years. In relation to older women, younger women have more adverse pathologic features and have a poorer prognosis. Younger age, per se, is not a contraindication to breast-conserving surgery. In node-negative young women, the benefits of adjuvant chemotherapy need to be considered in relation to the short- and long-term risks of treatment. A strong support system should be in place to deal with the adverse psychosocial impact of the disease.

  1. In Vivo Fluorescence Confocal Microscopy to Investigate the Role of RhoC in Inflammatory Breast Cancer

    DTIC Science & Technology

    2005-04-01

    H, Heike Y, Kawamoto S, Brechbiel MW, Kasumi F, Iwanaga T, Konishi F, Terada M, Wakasugi H: Hemodynamics in vasculogenic mimicry and angiogenesis of...inflammatory breast cancer xenograft. Cancer Res 2002, 62: 560-566. 27. Shirakawa K, Tsuda H, Heike Y, Kato K, Asada R, Inomata M, Sasaki H, Kasumi F

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

    ClinicalTrials.gov

    2017-09-18

    Estrogen Receptor-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Ductal Breast Carcinoma With Predominant Intraductal Component; 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

  3. Can We Prevent Breast Cancer?

    PubMed Central

    Saadat, Sabiha

    2008-01-01

    Breast cancer is the second most common cancer in the world and the most common cancer in females accounting to 23% of all cases. Between January 1998 and December 2004–2004, 6,882 cases were reported from all GCC states accounting to 11.8% from all cancers and 22.7% from cancers in females. An ASR/100,000 woman was 46.4 from Bahrain, 44.3 from Kuwait, 35.5 from Qatar, 19.2 from UAE, 14.2 from Oman and 12.9 from KSA. Breast cancer is the most frequent cancer in Arab women constituting 14–42% of all women cancers. Breast cancer in Arab countries presents almost 10 yrs younger than in USA and Europe. Median age at presentation is 48–52 and 50% of all cases are below the age of 50 where as only 25% of cases in industrialized nations are below the age of 50 yrs. What we need to fight this deadly disease is opening of screening centers with trained physicians equipped with ultrasound, x-ray unit, a pathology lab and most of all a system where a patient is seen urgently on referral to a secondary level care. Health education campaigns should be organized, female medical students should be encouraged to be general surgeons in a community where social customs still have value. PMID:21475500

  4. Cytokines, Neovascularization and Breast Cancer

    DTIC Science & Technology

    1995-10-01

    which support tumor growth and metastasis. In order to test our hypothesis, we are examining t ie expression of 11-8 antigen in human breast tissue using...Revised 1985). S4 For the protection of human subjects, the investigator(s) adhered to policies of applicable Federal Law 45 CFR 46. In conducting...Contents INTRODUCTION 5 BODY: EXPERIMENTAL METHODS AND RESULTS 6 Specific Aim I- To characterize IL-8 expression in human breast cancer 6 Study IA- To

  5. Partial breast irradiation for early breast cancer.

    PubMed

    Lehman, Margot; Hickey, Brigid E; Francis, Daniel P; See, Adrienne M

    2014-06-18

    Breast conserving therapy for women with breast cancer consists of local excision of the tumour (achieving clear margins) followed by radiation therapy (RT). RT is given to sterilize tumour cells that may remain after surgery to decrease the risk of local tumour recurrence. Most true recurrences occur in the same quadrant as the original tumour. Whole breast RT may not protect against the development of a new primary cancer developing in other quadrants of the breast. In this Cochrane Review, we investigated the role of delivering radiation to a limited volume of the breast around the tumour bed (partial breast irradiation: PBI) sometimes with a shortened treatment duration (accelerated partial breast irradiation: APBI). To determine whether PBI/APBI is equivalent to or better than conventional or hypofractionated WBRT after breast conservation therapy for early-stage breast cancer. We searched the Cochrane Breast Cancer Group Specialised Register (07 November 2013), CENTRAL (2014, Issue 3), MEDLINE (January 1966 to 11 April 2014), EMBASE (1980 to 11 April 2014), CINAHL (11 April 2014) and Current Contents (11 April 2014). Also we searched the International Standard Randomised Controlled Trial Number Register, the World Health Organization's International Clinical Trials Registry Platform (07 November 2013) and US clinical trials registry (www.clinicaltrials.gov) (22 April 2014). We searched for grey literature: Open Grey (23 April 2014), reference lists of articles, a number of conference proceedings and published abstracts, and did not apply any language restrictions. Randomised controlled trials (RCTs) without confounding and evaluating conservative surgery plus PBI/APBI versus conservative surgery plus whole breast RT. We included both published and unpublished trials. Three review authors (ML, DF and BH) performed data extraction and resolved any disagreements through discussion. We entered data into Review Manager for analysis. BH and ML assessed trials

  6. EGCG, a major green tea catechin suppresses breast tumor angiogenesis and growth via inhibiting the activation of HIF-1α and NFκB, and VEGF expression.

    PubMed

    Gu, Jian-Wei; Makey, Kristina L; Tucker, Kevan B; Chinchar, Edmund; Mao, Xiaowen; Pei, Ivy; Thomas, Emily Y; Miele, Lucio

    2013-05-02

    The role of EGCG, a major green tea catechin in breast cancer therapy is poorly understood. The present study tests the hypothesis that EGCG can inhibit the activation of HIF-1α and NFκB, and VEGF expression, thereby suppressing tumor angiogenesis and breast cancer progression. Sixteen eight-wk-old female mice (C57BL/6 J) were inoculated with 10^6 E0771 (mouse breast cancer) cells in the left fourth mammary gland fat pad. Eight mice received EGCG at 50-100 mg/kg/d in drinking water for 4 weeks. 8 control mice received drinking water only. Tumor size was monitored using dial calipers. At the end of the experiment, blood samples, tumors, heart and limb muscles were collected for measuring VEGF expression using ELISA and capillary density (CD) using CD31 immunohistochemistry. EGCG treatment significantly reduced tumor weight over the control (0.37 ± 0.15 vs. 1.16 ± 0.30 g; P < 0.01), tumor CD (109 ± 20 vs. 156 ± 12 capillary #/mm^2; P < 0.01), tumor VEGF expression (45.72 ± 1.4 vs. 59.03 ± 3.8 pg/mg; P < 0.01), respectively. But, it has no effects on the body weight, heart weight, angiogenesis and VEGF expression in the heart and skeletal muscle of mice. EGCG at 50 μg/ml significantly inhibited the activation of HIF-1α and NFκB as well as VEGF expression in cultured E0771 cells, compared to the control, respectively. These findings support the hypothesis that EGCG, a major green tea catechin, directly targets both tumor cells and tumor vasculature, thereby inhibiting tumor growth, proliferation, migration, and angiogenesis of breast cancer, which is mediated by the inhibition of HIF-1α and NFκB activation as well as VEGF expression.

  7. EGCG, a major green tea catechin suppresses breast tumor angiogenesis and growth via inhibiting the activation of HIF-1α and NFκB, and VEGF expression

    PubMed Central

    2013-01-01

    The role of EGCG, a major green tea catechin in breast cancer therapy is poorly understood. The present study tests the hypothesis that EGCG can inhibit the activation of HIF-1α and NFκB, and VEGF expression, thereby suppressing tumor angiogenesis and breast cancer progression. Sixteen eight-wk-old female mice (C57BL/6 J) were inoculated with 10^6 E0771 (mouse breast cancer) cells in the left fourth mammary gland fat pad. Eight mice received EGCG at 50–100 mg/kg/d in drinking water for 4 weeks. 8 control mice received drinking water only. Tumor size was monitored using dial calipers. At the end of the experiment, blood samples, tumors, heart and limb muscles were collected for measuring VEGF expression using ELISA and capillary density (CD) using CD31 immunohistochemistry. EGCG treatment significantly reduced tumor weight over the control (0.37 ± 0.15 vs. 1.16 ± 0.30 g; P < 0.01), tumor CD (109 ± 20 vs. 156 ± 12 capillary #/mm^2; P < 0.01), tumor VEGF expression (45.72 ± 1.4 vs. 59.03 ± 3.8 pg/mg; P < 0.01), respectively. But, it has no effects on the body weight, heart weight, angiogenesis and VEGF expression in the heart and skeletal muscle of mice. EGCG at 50 μg/ml significantly inhibited the activation of HIF-1α and NFκB as well as VEGF expression in cultured E0771 cells, compared to the control, respectively. These findings support the hypothesis that EGCG, a major green tea catechin, directly targets both tumor cells and tumor vasculature, thereby inhibiting tumor growth, proliferation, migration, and angiogenesis of breast cancer, which is mediated by the inhibition of HIF-1α and NFκB activation as well as VEGF expression. PMID:23638734

  8. Multiparametric Breast MRI of Breast Cancer

    PubMed Central

    Rahbar, Habib; Partridge, Savannah C.

    2015-01-01

    Synopsis Breast MRI has increased in popularity over the past two decades due to evidence for its high sensitivity for cancer detection. Current clinical MRI approaches rely on the use of a dynamic contrast enhanced (DCE-MRI) acquisition that facilitates morphologic and semi-quantitative kinetic assessments of breast lesions. The use of more functional and quantitative parameters, such as pharmacokinetic features from high temporal resolution DCE-MRI, apparent diffusion coefficient (ADC) and intravoxel incoherent motion (IVIM) on diffusion weighted MRI, and choline concentrations on MR spectroscopy, hold promise to broaden the utility of MRI and improve its specificity. However, due to wide variations in approach among centers for measuring these parameters and the considerable technical challenges, robust multicenter data supporting their routine use is not yet available, limiting current applications of many of these tools to research purposes. PMID:26613883

  9. Multiple primary breast and thyroid cancer.

    PubMed Central

    Ron, E.; Curtis, R.; Hoffman, D. A.; Flannery, J. T.

    1984-01-01

    The occurrence of breast and thyroid multiple primary cancers was evaluated using data from the Connecticut Tumor Registry. The study population consisted of 1618 women with primary thyroid cancer and 39,194 women with primary breast cancer diagnosed between 1935 and 1978. Thirty-four thyroid cancer patients subsequently developed breast cancer and 24 breast cancer patients later had thyroid cancer. A significantly elevated risk of thyroid cancer following breast cancer (SIR = 1.68) and breast cancer following thyroid cancer (SIR = 1.89) was demonstrated. The finding was even more notable when compared with the risks obtained for other sites. The elevated risk was particularly evident in women under 40 years of age at time of diagnosis of the first cancer. Analysis by histologic type revealed that the highest risk of second primary breast cancer was found among patients with follicular or mixed papillary-follicular thyroid cancer. Women under age 40 with follicular carcinoma had a 10-fold risk of developing breast cancer (4 observed, 0.4 expected). An enhanced risk of second primary tumours was evident for the entire period after treatment of the first primary, although it was highest within one year after diagnosis of the first primary. This may be due to the close medical surveillance of cancer patients which would increase early diagnosis of second tumours. Our findings suggest that breast and thyroid cancer may share common aetiologic features. PMID:6691901

  10. Multiple primary breast and thyroid cancer.

    PubMed

    Ron, E; Curtis, R; Hoffman, D A; Flannery, J T

    1984-01-01

    The occurrence of breast and thyroid multiple primary cancers was evaluated using data from the Connecticut Tumor Registry. The study population consisted of 1618 women with primary thyroid cancer and 39,194 women with primary breast cancer diagnosed between 1935 and 1978. Thirty-four thyroid cancer patients subsequently developed breast cancer and 24 breast cancer patients later had thyroid cancer. A significantly elevated risk of thyroid cancer following breast cancer (SIR = 1.68) and breast cancer following thyroid cancer (SIR = 1.89) was demonstrated. The finding was even more notable when compared with the risks obtained for other sites. The elevated risk was particularly evident in women under 40 years of age at time of diagnosis of the first cancer. Analysis by histologic type revealed that the highest risk of second primary breast cancer was found among patients with follicular or mixed papillary-follicular thyroid cancer. Women under age 40 with follicular carcinoma had a 10-fold risk of developing breast cancer (4 observed, 0.4 expected). An enhanced risk of second primary tumours was evident for the entire period after treatment of the first primary, although it was highest within one year after diagnosis of the first primary. This may be due to the close medical surveillance of cancer patients which would increase early diagnosis of second tumours. Our findings suggest that breast and thyroid cancer may share common aetiologic features.

  11. MicroRNA-17~92 inhibits colorectal cancer progression by targeting angiogenesis.

    PubMed

    Ma, Huabin; Pan, Jin-Shui; Jin, Li-Xin; Wu, Jianfeng; Ren, Yan-Dan; Chen, Pengda; Xiao, Changchun; Han, Jiahuai

    2016-07-01

    The miR-17~92 microRNA (miRNA) cluster host gene is upregulated in a broad spectrum of human cancers including colorectal cancer (CRC). Previous studies have shown that miR-17~92 promotes tumorigenesis and cancer angiogenesis in some tumor models. However, its role in the initiation and progression of CRC remains unknown. In this study, we found that transgenic mice overexpressing miR-17~92 specifically in epithelial cells of the small and large intestines exhibited decreased tumor size and tumor angiogenesis in azoxymethane and dextran sulfate sodium salt (AOM-DSS)-induced CRC model as compared to their littermates control. Further study showed that miR-17~92 inhibited the progression of CRC via suppressing tumor angiogenesis through targeting multiple tumor angiogenesis-inducing genes, TGFBR2, HIF1α, and VEGFA in vivo and in vitro. Collectively, we demonstrated that miR-17~92 suppressed tumor progression by inhibiting tumor angiogenesis in a genetically engineered mouse model, indicating the presence of cellular context-dependent pro- and anti-cancer effects of miR-17~92.

  12. Inhibition of tumor angiogenesis by tumstatin: insights into signaling mechanisms and implications in cancer regression.

    PubMed

    Sudhakar, Akulapalli; Boosani, Chandra S

    2008-12-01

    Growing tumors develop additional new blood vessels to meet the demand for adequate nutrients and oxygen, a process called angiogenesis. Cancer is a highly complex disease promoted by excess angiogenesis; interfering with this process poses for an attractive approach for controlling tumor growth. This hypothesis led to the identification of endogenous angiogenesis inhibitors generated from type IV collagen, a major component of vascular basement membrane (VBM). Type IV collagen and the angiogenesis inhibitors derived from it are involved in complex roles, than just the molecular construction of basement membranes. Protease degradation of collagens in VBM occurs in various physiological and pathological conditions and produces several peptides. Some of these peptides are occupied in the regulation of functions conflicting from those of their original integral molecules. Tumstatin (alpha3(IV)NC1), a proteolytic C-terminal non-collagenous (NC1) domain from type IV collagen alpha3 chain has been highlighted recently because of its potential role in anti-angiogenesis, however its biological actions are not limited to these processes. alpha3(IV)NC1 inhibits proliferation by promoting endothelial cell apoptosis and suppresses diverse tumor angiogenesis, thus making it a potential candidate for future cancer therapy. The present review surveys the physiological functions of type IV collagen and discovery of alpha3(IV)NC1 as an antiangiogenic protein with a comprehensive overview of the knowledge gained by us towards understanding its signaling mechanisms.

  13. DNA damage and breast cancer

    PubMed Central

    Davis, Jennifer D; Lin, Shiaw-Yih

    2011-01-01

    Cancer is intimately related to the accumulation of DNA damage, and repair failures (including mutation prone repair and hyperactive repair systems). This article relates current clinical categories for breast cancer and their common DNA damage repair defects. Information is included on the potential for accumulation of DNA damage in the breast tissue of a woman during her lifetime and the role of DNA damage in breast cancer development. We then cover endogenous and exogenous sources of DNA damage, types of DNA damage repair and basic signal transduction pathways for three gene products involved in the DNA damage response system; namely BRCA1, BRIT1 and PARP-1. These genes are often considered tumor suppressors because of their roles in DNA damage response and some are under clinical investigation as likely sources for effective new drugs to treat breast cancers. Finally we discuss some of the problems of DNA damage repair systems in cancer and the conundrum of hyper-active repair systems which can introduce mutations and confer a survival advantage to certain types of cancer cells. PMID:21909479

  14. Inhibition of Breast Tumor Cell Growth by Ectopic Expression of p16/INK4A Via Combined Effects of Cell Cycle Arrest, Senescence and Apoptotic Induction, and Angiogenesis Inhibition.

    PubMed

    Lu, Yi; Zhang, Xiongwen; Zhang, Jun

    2012-01-01

    p16-mediated inhibition of cancer cell proliferation and tumor suppression have been studied before,; the common consensus is that p16's cell-cycle arrest function plays a primary role in these actions, with some additional apoptotic induction by p16. However, other effects of p16 that may potentially contribute to p16-mediated anti-tumor ability have not been well studied. The emerging data including ours indicated that p16 contributes its anti-cancer ability by inducing tumor cells to senescence. Moreover, we showed that p16 inhibits breast cancer cell growth by inhibiting the VEGF signaling pathway and angiogenesis. In this study, we used adenoviral-mediated p16 expression (AdRSVp16) and breast cancer cell line MDA-MB-231 as the model to simultaneously analyze all these p16's anti-tumor functions. We demonstrated that adenoviral-mediated p16 expression exhibited multiple anti-tumor functions by simultaneously suppressing in vitro growth and in vivo angiogenesis of breast cancer cells, blocking cell division, as well as inducing senescence and apoptosis. The in vivo study implies that p16's effect on anti-angiogenesis may play a more significant role than its anti-cell proliferation in the overall suppression of tumor growth. These results suggest, for the first time, that AdRSVp16-mediated tumor suppression results from a combination of p16's multiple anti-tumor functions including p16's well-known anti-proliferation/cell division function, apoptotic and senescence induction function, and its lesser-known/under-investigated anti-angiogenesis function. These combined results strongly indicate that p16 gene therapy has a multi-module platform with different anti-tumor functions; therefore, this study justifies and promotes the viral-mediated p16 gene therapy as a promising and powerful treatment approach for cancer patients due to p16's multiple anti-tumor functions.

  15. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues. Here, two High-Aspect Ratio Vessels turn at about 12 rmp to keep breast tissue constructs suspended inside the culture media. Syringes allow scientists to pull for analysis during growth sequences. The tube in the center is a water bubbler that dehumidifies the air to prevent evaporation of the media and thus the appearance of destructive bubbles in the bioreactor.

  16. Inflammatory breast cancer: an overview.

    PubMed

    van Uden, D J P; van Laarhoven, H W M; Westenberg, A H; de Wilt, J H W; Blanken-Peeters, C F J M

    2015-02-01

    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 multimodal therapeutic approach has significantly improved patient survival. However, the median overall survival among women with IBC is still poor. By elucidating the biologic characteristics of IBC, new treatment options may become available. We performed a comprehensive review of the English-language literature on IBC through computerized literature searches. The objective of the current review is to present an overview of the literature related to the biology, imaging and multidisciplinary treatment of inflammatory breast cancer.

  17. Tamoxifen for breast cancer prevention

    SciTech Connect

    Jordan, V.C.

    1995-02-01

    The case for tamoxifen to be tested as a preventive for breast cancer has merit. Animal studies demonstrate that tamoxifen prevents mammary carcinogenesis and clinical studies now confirm that adjuvant tamoxifen therapy is the only systemic treatment that will prevent contralateral breast cancer. Developing clinical studies confirm the laboratory data that tamoxifen will maintain post-menopausal bone density in the lumbar spine and the neck of the femur; two important skeletal sites for the ultimate prevention of osteoporosis. However, a most important target site-specific effect of tamoxifen is the decrease in low-density lipoprotein cholesterol levels in postmenopausal women. This positive property of tamoxifen may be responsible for the recorded decreases in hospital visits for the treatment of cardiac conditions and the significant decrease in fatal myocardial infarction for women treated with 5 years of adjuvant tamoxifen. These data provide the scientific basis to undertake randomized, placebocontrolled clinical trials to test the worth of tamoxifen to prevent breast cancer.

  18. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues. Here, two High-Aspect Ratio Vessels turn at about 12 rmp to keep breast tissue constructs suspended inside the culture media. Syringes allow scientists to pull for analysis during growth sequences. The tube in the center is a water bubbler that dehumidifies the air to prevent evaporation of the media and thus the appearance of destructive bubbles in the bioreactor.

  19. Stabilized epoxygenated fatty acids regulate inflammation, pain, angiogenesis and cancer

    PubMed Central

    Zhang, Guodong; Kodani, Sean; Hammock, Bruce D.

    2014-01-01

    Epoxygenated fatty acids (EpFAs), which are lipid mediators produced by cytochrome P450 epoxygenases from polyunsaturated fatty acids, are important signaling molecules known to regulate various biological processes including inflammation, pain and angiogenesis. The EpFAs are further metabolized by soluble epoxide hydrolase (sEH) to form fatty acid diols which are usually less-active. Pharmacological inhibitors of sEH that stabilize endogenous EpFAs are being considered for human clinical uses. Here we review the biology of ω-3 and ω-6 EpFAs on inflammation, pain, angiogenesis and tumorigenesis. PMID:24345640

  20. Breast cancer risk assessment in primary care.

    PubMed

    Brown, Shannon Lynn; Kartoz, Connie

    2014-01-01

    Breast cancer is the most common cancer (when excluding skin cancers) in women and the second most common cause of cancer death in women, with a lifetime prevalence of 12.5% (, ; ). Breast cancer screening reduces risk of cancer death, thereby increasing rate of survival to up to 89% for women with stage 1 and 2 breast cancer (; ). Despite these data, undue harm may occur with unnecessary screening because overidentification of risk, and excessive, costly biopsies may result. Costs and benefits of screening must be weighed. Nurses at all levels can play a pivotal role in promotion of appropriate breast cancer screening and subsequently breast cancer prevention by using accurate screening tools, such as the Tyrer-Cuzick model. Although there are some limitations with this tool, screening at the primary care level has demonstrated improved clinical outcomes (). Its use can help nurses accurately assess a woman's breast cancer risk, by promoting appropriate screening at the primary care level ().