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Sample records for breast cancer growth

  1. 6 Common Cancers - Breast Cancer

    Science.gov (United States)

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

  2. 6 Common Cancers - Breast Cancer

    Science.gov (United States)

    ... 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 ...

  3. Silencing NOTCH signaling causes growth arrest in both breast cancer stem cells and breast cancer cells

    Science.gov (United States)

    Suman, S; Das, T P; Damodaran, C

    2013-01-01

    Background: Breast cancer stem cells (BCSCs) are characterized by high aldehyde dehydrogenase (ALDH) enzyme activity and are refractory to current treatment modalities, show a higher risk for metastasis, and influence the epithelial to mesenchymal transition (EMT), leading to a shorter time to recurrence and death. In this study, we focused on examination of the mechanism of action of a small herbal molecule, psoralidin (Pso) that has been shown to effectively suppress the growth of BSCSs and breast cancer cells (BCCs), in breast cancer (BC) models. Methods: ALDH− and ALDH+ BCCs were isolated from MDA-MB-231 cells, and the anticancer effects of Pso were measured using cell viability, apoptosis, colony formation, invasion, migration, mammosphere formation, immunofluorescence, and western blot analysis. Results: Psoralidin significantly downregulated NOTCH1 signaling, and this downregulation resulted in growth inhibition and induction of apoptosis in both ALDH− and ALDH+ cells. Molecularly, Pso inhibited NOTCH1 signaling, which facilitated inhibition of EMT markers (β-catenin and vimentin) and upregulated E-cadherin expression, resulting in reduced migration and invasion of both ALDH− and ALDH+ cells. Conclusion: Together, our results suggest that inhibition of NOTCH1 by Pso resulted in growth arrest and inhibition of EMT in BCSCs and BCCs. Psoralidin appears to be a novel agent that targets both BCSCs and BCCs. PMID:24129237

  4. Nonlinear Growth Kinetics of Breast Cancer Stem Cells: Implications for Cancer Stem Cell Targeted Therapy

    OpenAIRE

    Liu, Xinfeng; Johnson, Sara; Liu, Shou; Kanojia, Deepak; Yue, Wei; Singn, Udai; Wang, Qian; Wang, Qi; Nie, Qing; Chen, Hexin

    2013-01-01

    Cancer stem cells (CSCs) have been identified in primary breast cancer tissues and cell lines. The CSC population varies widely among cancerous tissues and cell lines, and is often associated with aggressive breast cancers. Despite of intensive research, how the CSC population is regulated within a tumor is still not well understood so far. In this paper, we present a mathematical model to explore the growth kinetics of CSC population both in vitro and in vivo. Our mathematical models and sup...

  5. Breast Cancer

    Science.gov (United States)

    Breast cancer affects one in eight women during their lives. Breast cancer kills more women in the United States than ... cancer. No one knows why some women get breast cancer, but there are a number of risk factors. ...

  6. What Is Breast Cancer?

    Science.gov (United States)

    ... Next Topic Types of breast cancers What is breast cancer? Breast cancer starts when cells in the breast ... breast cancer? ” and Non-cancerous Breast Conditions . How Breast Cancer Spreads Breast cancer can spread through the lymph ...

  7. Growth Inhibition of Breast Cancer in Rat by AAV Mediated Angiostatin Gene

    Institute of Scientific and Technical Information of China (English)

    LI Ran; CHEN Hong; REN Chang-shan

    2007-01-01

    Objective: To observe growth inhibition effect of adeno-associated viral vectors (AAV) mediated angiostatin (ANG) gene on implanted breast cancer in rat and its mechanism. Methods: Gene transfer technique was used to transfer AAV-ANG to the tumor. Growth curves were drawn to observe the growth of breast cancer implanted in rat, and immunohistochemical method was used to detect the effects of angiostatin on microvesel density (MVD) of breast cancer implanted in rat. Results: Angiostatin inhibited the growth of breast cancer implanted in rat and decreased the microvessel density of tumor. Conclusion: Expression of an angiostatin transgene can suppress the growth of breast cancer implanted in rat through the inhibition of the growth of microvessels, surggesting that angiostatin gene transfer technique may be effective against breast cancer.

  8. Epidermal growth factor receptor (EGFR) polymorphisms and breast cancer among Hispanic and non-Hispanic white women: the Breast Cancer Health Disparities Study

    OpenAIRE

    Connor, Avonne E.; Baumgartner, Richard N.; Baumgartner, Kathy B.; Pinkston, Christina M; John, Esther M.; Torres-Mejía, Gabriela; Hines, Lisa M.; Giuliano, Anna R.; Wolff, Roger K.; Slattery, Martha L.

    2013-01-01

    The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptor tyrosine kinases, functions in cellular processes essential to the development of cancer. Overexpression of EGFR in primary breast tumors has been linked with poor prognosis. We investigated the associations between 34 EGFR tagging SNPs and breast cancer risk and breast cancer-specific mortality in 4,703 Hispanic and 3,030 non-Hispanic white women from the Breast Cancer Health Disparities Study. We evaluated ...

  9. Post-traumatic growth among elderly women with breast cancer compared to breast cancer-free women

    DEFF Research Database (Denmark)

    Brix, Sofie Andersen; Bidstrup, Pernille Envold; Christensen, Jane;

    2013-01-01

    Although breast cancer (BC) may have negative psychological sequelae, it may also be experienced as an existential challenge, which can derive personal growth. Only one study has been conducted, however, on whether women with BC experience more post-traumatic growth (PTG) than BC-free women. We...

  10. Differential Expression of Growth Factor Receptors and Membrane-Bound Tumor Markers for Imaging in Male and Female Breast Cancer

    OpenAIRE

    Vermeulen, Jeroen F.; Robert Kornegoor; Elsken van der Wall; Petra van der Groep; Paul J. van Diest

    2013-01-01

    INTRODUCTION: Male breast cancer accounts for 0.5-1% of all breast cancers and is generally diagnosed at higher stage than female breast cancers and therefore might benefit from earlier detection and targeted therapy. Except for HER2 and EGFR, little is known about expression of growth factor receptors in male breast cancer. We therefore investigated expression profiles of growth factor receptors and membrane-bound tumor markers in male breast cancer and gynecomastia, in comparison with femal...

  11. CXCL12 chemokine expression suppresses human breast cancer growth and metastasis in vitro and in vivo

    OpenAIRE

    Lv, Zhi-Dong; Kong, Bin; Liu, Xiang-Ping; Dong, Qian; Niu, Hai-tao; Wang, Yong-Hua; Li, Fu-Nian; Wang, Hai-Bo

    2014-01-01

    Chemokine receptors are now known to play an important role in cancer growth and metastasis. However, there is little information regarding chemokine expression in breast cancer. The aim of this study was to evaluate CXCL12 expression in breast cancer and to investigate the question of whether reduced expression of CXCL12 may have any pathological significance in breast cancer development or progression. In this study, we performed western blotting and immunohistochemistry to evaluate the exp...

  12. Nonlinear Growth Kinetics of Breast Cancer Stem Cells: Implications for Cancer Stem Cell Targeted Therapy

    Science.gov (United States)

    Liu, Xinfeng; Johnson, Sara; Liu, Shou; Kanojia, Deepak; Yue, Wei; Singn, Udai; Wang, Qian; Wang, Qi; Nie, Qing; Chen, Hexin

    2013-08-01

    Cancer stem cells (CSCs) have been identified in primary breast cancer tissues and cell lines. The CSC population varies widely among cancerous tissues and cell lines, and is often associated with aggressive breast cancers. Despite of intensive research, how the CSC population is regulated within a tumor is still not well understood so far. In this paper, we present a mathematical model to explore the growth kinetics of CSC population both in vitro and in vivo. Our mathematical models and supporting experiments suggest that there exist non-linear growth kinetics of CSCs and negative feedback mechanisms to control the balance between the population of CSCs and that of non-stem cancer cells. The model predictions can help us explain a few long-standing questions in the field of cancer stem cell research, and can be potentially used to predict the efficicacy of anti-cancer therapy.

  13. Can supplementary dietary fibre suppress breast cancer growth?

    OpenAIRE

    Stoll, B. A.

    1996-01-01

    Case-control studies in diverse populations around the world have reported a lower risk of breast cancer in association with higher intake of dietary fibre and complex carbohydrates. Although this has not been confirmed in prospective studies in the USA, the observations have prompted the hypothesis that prolonged use of dietary fibre supplements might reduce breast cancer risk in high-incidence populations. Several possible mechanisms of action have been suggested, all involving a reduction ...

  14. Breast Cancer

    Science.gov (United States)

    ... I found something when I did my breast self-exam. What should I do now? How often should I have mammograms? I have breast cancer. What are my treatment options? How often should I do breast self-exams? I have breast cancer. Is my daughter ...

  15. Inhibition of Human Breast Cancer Xenograft Growth by Cruciferous Vegetable Constituent Benzyl Isothiocyanate

    OpenAIRE

    Warin, Renaud; Xiao, Dong; Arlotti, Julie A.; Bommareddy, Ajay; Singh, Shivendra V

    2010-01-01

    Benzyl isothiocyanate (BITC), a constituent of cruciferous vegetables such as gardencress, inhibits growth of human breast cancer cell lines in culture. The present study was undertaken to determine in vivo efficacy of BITC against MDA-MB-231 human breast cancer xenografts. The BITC administration retarded growth of MDA-MB-231 cells subcutaneously implanted in female nude mice without causing weight loss or any other side effects. The BITC-mediated suppression of MDA-MB-231 xenograft growth c...

  16. Breast Cancer

    Science.gov (United States)

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

  17. Breast Cancer Screening

    Science.gov (United States)

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

  18. Tyrosine kinase signalling in breast cancer: Epidermal growth factor receptor and c-Src interactions in breast cancer

    International Nuclear Information System (INIS)

    Both the non-receptor tyrosine kinase, c-Src, and members of the epidermal growth factor (EGF) receptor family are overexpressed in high percentages of human breast cancers. Because these molecules are plasma membrane-associated and involved in mitogenesis, it has been speculated that they function in concert with one another to promote breast cancer development and progression. Evidence to date supports a model wherein c-Src potentiates the survival, proliferation and tumorigenesis of EGF receptor family members, in part by associating with them. Phosphorylation of the EGF receptor by c-SRC is also critical for mitogenic signaling initiated by the EGF receptor itself, as well as by several G-protein coupled receptors (GPCRs), a cytokine receptor, and the estrogen receptor. Thus, c-Src appears to have pleiotropic effects on cancer cells by modulating the action of multiple growth-promoting receptors

  19. Increased concentrations of growth factors and activation of the EGFR system in breast cancer

    DEFF Research Database (Denmark)

    Aalund Olsen, Dorte; Bechmann, Troels; Østergaard, Birthe;

    2012-01-01

    In this study the total and phosphorylated amount of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) were measured together with EGFR ligands in tissue samples of breast cancer patients in order to investigate interrelations and possible prognostic values.......In this study the total and phosphorylated amount of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) were measured together with EGFR ligands in tissue samples of breast cancer patients in order to investigate interrelations and possible prognostic values....

  20. Relaxins enhance growth of spontaneous murine breast cancers as well as metastatic colonization of the brain.

    OpenAIRE

    Binder, Claudia; Chuang, Eugenia; Habla, Christina; Bleckmann, Annalen; Schulz, Matthias; Bathgate, Ross; Einspanier, Almuth

    2014-01-01

    Relaxins are known for their tissue remodeling capacity which is also a hallmark of cancer progression. However, their role in the latter context is still unclear, particularly in breast cancer. In a mouse model with spontaneously arising breast cancer due to erbB2-overexpression we show that exposure to porcine relaxin results in significantly enhanced tumour growth as compared to control animals. This is accompanied by increased serum concentrations of progesterone and estradiol as well as ...

  1. The subcellular localization of IGFBP5 affects its cell growth and migration functions in breast cancer

    OpenAIRE

    Sahin Aysegul; Hu Limei; Akkiprik Mustafa; Hao Xishan; Zhang Wei

    2009-01-01

    Abstract Background Insulin-like growth factor binding protein 5 (IGFBP5) has been shown to be associated with breast cancer metastasis in clinical marker studies. However, a major difficulty in understanding how IGFBP5 functions in this capacity is the paradoxical observation that ectopic overexpression of IGFBP5 in breast cancer cell lines results in suppressed cellular proliferation. In cancer tissues, IGFBP5 resides mainly in the cytoplasm; however, in transfected cells, IGFBP5 is mainly ...

  2. In vivo measurement of tumor estradiol and Vascular Endothelial Growth Factor in breast cancer patients

    International Nuclear Information System (INIS)

    Angiogenesis, crucial for tumor progression, is a process regulated in the tissue micro-environment. Vascular endothelial growth factor (VEGF) is a potent stimulatory factor of angiogenesis and a negative prognostic indicator of breast cancer. VEGF is biologically active in the extracellular space and hitherto, there has been a lack of techniques enabling sampling of angiogenic molecules such as VEGF in situ. The majority of breast cancers are estrogen-dependent, and estrogen has been shown to regulate VEGF in normal breast tissue and experimental breast cancer. We investigated if microdialysis may be applicable in human breast cancer for sampling of extracellular VEGF in situ and to explore if there is an association with local estradiol and VEGF levels in normal and cancerous breast tissue. Microdialysis was used to sample VEGF and estradiol in tumors and adjacent normal breast tissue in postmenopausal breast cancer patients. VEGF and estradiol were also measured in plasma, and immunohistochemical staining for VEGF was performed on tumor sections. We show that in vivo levels of extracellular VEGF were significantly higher in breast cancer tumors than in normal adjacent breast tissue. There was a significant positive correlation between estradiol and extracellular VEGF in normal breast tissue. However, no correlation was detected between estradiol and VEGF in tumors or between tumor VEGF and plasma VEGF. We conclude that VEGF and estradiol correlates significantly in normal breast tissue. Microdialysis may be used to provide novel insight in breast tumor biology and the regulation of molecules in the extracellular space of human breast tumors in vivo

  3. Breast cancer

    Science.gov (United States)

    ... perform breast self-exams each month. However, the importance of self-exams for detecting breast cancer is ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  4. Treatment with kaempferol suppresses breast cancer cell growth caused by estrogen and triclosan in cellular and xenograft breast cancer models.

    Science.gov (United States)

    Kim, Seung-Hee; Hwang, Kyung-A; Choi, Kyung-Chul

    2016-02-01

    As a phytoestrogen, kaempferol (Kaem) is one of bioflavonoids, which are found in a variety of vegetables including broccoli, tea and tomato. In this study, the antiproliferative effects of Kaem in triclosn (TCS)-induced cell growth were examined in MCF-7 breast cancer cells. TCS promoted the cell viability of MCF-7 cells via estrogen receptor α (ERα) as did 17β-estradiol (E2), a positive control. On the other hand, Kaem significantly suppressed E2 or TCS-induced cell growth. To elucidate the molecular mechanisms of TCS and Kaem, alterations in the expressions of cell cycle, apoptosis and metastasis-related genes were identified using western blot assay. The treatment of the cells with TCS up-regulated the protein expressions of cyclin D1, cyclin E and cathepsin D, while down-regulated p21 and bax expressions. Kaem reversed TCS-induced gene expressions in an opposite manner. The phosphorylation of IRS-1, AKT, MEK1/2 and ERK was increased by TCS, indicating that TCS induced MCF-7 cell proliferation via nongenomic ER signaling pathway associated with IGF-1R. Kaem presented an antagonistic activity on this signaling by down-regulating the protein expression of pIRS-1, pAkt and pMEK1/2 promoted by E2 or TCS. In an in vivo xenografted mouse model, tumor growth was induced by treatment with E2 or TCS, which was identified in the measurement of tumor volume, hematoxylin and eosin staining, bromodeoxyuridine and immunohistochemistry assay. On the contrary, E2 or TCS-induced breast tumor growth was inhibited by co-treatment with Kaem, which is consistent with in vitro results. Taken together, these results revealed that Kaem has an anticancer effect against procancer activity of E2 or TCS, a xenoestrogen, in breast cancer and may be suggested as a prominent agent to neutralize breast cancer risk caused by TCS. PMID:26878784

  5. Elevated expression of protein regulator of cytokinesis 1, involved in the growth of breast cancer cells.

    Science.gov (United States)

    Shimo, Arata; Nishidate, Toshihiko; Ohta, Tomohiko; Fukuda, Mamoru; Nakamura, Yusuke; Katagiri, Toyomasa

    2007-02-01

    To elucidate molecular mechanisms of mammary carcinogenesis and discover novel therapeutic targets for breast cancer, we previously carried out a genome-wide expression profile analysis of 81 breast cancer cases by means of a combination of cDNA microarray and laser microbeam microdissection. Among the upregulated genes, we focused on the functional significance of protein regulator of cytokinesis 1 (PRC1) in the development of breast cancer. Western blot analysis using breast cancer cell lines revealed a significant increase in endogenous PRC1 levels in G(2)/M phase. Treatment of breast cancer cells with small interfering RNA against PRC1 effectively suppressed its expression and inhibited the growth of breast cancer cell lines T47D and HBC5. Furthermore, we found an interaction between PRC1 and kinesin family member 2C/mitotic centromere-associated kinesin (KIF2C/MCAK) by coimmunoprecipitation and immunoblotting using COS-7 cells, in which these molecules were introduced exogenously. These findings suggest the involvement of a PRC1-KIF2C/MCAK complex in breast tumorigenesis, and this complex should be a promising target for the development of novel treatments for breast cancer. PMID:17233835

  6. Trastuzumab Emtansine in Treating Older Patients With Human Epidermal Growth Factor Receptor 2-Positive Stage I-III Breast Cancer

    Science.gov (United States)

    2016-05-31

    Estrogen Receptor Negative; HER2 Positive Breast Carcinoma; Progesterone Receptor Negative; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIC Breast Cancer

  7. Decreased Autocrine EGFR Signaling in Metastatic Breast Cancer Cells Inhibits Tumor Growth in Bone and Mammary Fat Pad

    OpenAIRE

    Nickerson, Nicole K.; Mohammad, Khalid S.; Gilmore, Jennifer L.; Crismore, Erin; Bruzzaniti, Angela; Guise, Theresa A.; Foley, John

    2012-01-01

    Breast cancer metastasis to bone triggers a vicious cycle of tumor growth linked to osteolysis. Breast cancer cells and osteoblasts express the epidermal growth factor receptor (EGFR) and produce ErbB family ligands, suggesting participation of these growth factors in autocrine and paracrine signaling within the bone microenvironment. EGFR ligand expression was profiled in the bone metastatic MDA-MB-231 cells (MDA-231), and agonist-induced signaling was examined in both breast cancer and oste...

  8. Vascular endothelial growth factor and microvessel density for detection and prognostic evaluation of invasive breast cancer

    Institute of Scientific and Technical Information of China (English)

    Lukui Yang; Long Li; Xiangyu Cui; Dalei Yang

    2015-01-01

    Objective The purpose of this study was to evaluate the distribution of vascular endothelial growth factor (VEGF) and CD105-microvessel density (MVD) in invasive breast carcinomas. We also aimed to analyze the relationship between VEGF and MVD expression with other standard prognostic parameters associated with invasive breast cancer, such as size, grade, stage of the cancer, metastases, and tumor recurrence. Methods Immunohistochemistry via the Ultra SensitiveTM S-P method was used to detect VEGF and MVD expression in 128 cases of invasive breast carcinoma. Specimens were evaluated for CD105 expres-sion. Positively stained microvessels were counted in dense vascular foci under 400× magnification. MVD in the peripheral area adjacent to the lesion and in the central area within the lesion in invasive breast carcinomas and benign leisions groups were also assessed. Fifty cases of benign breast disease tissue were selected as the control group. Results Results showed that 64.1% of invasive breast cancer samples were VEGF-positive, higher than in benign breast disease tissue (22.0%, P 0.05). MVD of the peripheral area adja-cent to the lesion was significantly higher than those central area within the lesion in both invasive breast cancer and benign breast disease groups (P 50 years) or the two tumor diameter groups (≤2 cm vs.>2 cm), P > 0.05. Conclusion Overexpression of VEGF and MVD may be important biological markers for invasion and lymph node and distant metastases of invasive breast cancer. Combined detection of the two tumor mark-ers could provide better prognostic monitoring for disease recurrence and metastasis, as wel as aid with clinical staging of breast tumors. Prediction of the risk for metastasis and recurrence, as wel as recurrence patterns based on VEGF and MVD post-surgery, could aid design of better fol ow-up regimens and appro-priate treatment strategies for breast cancer patients.

  9. Breast Cancer Treatment

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Treatment (PDQ®)–Patient Version General Information About Breast Cancer Go to Health Professional Version Key Points Breast ...

  10. Stages of Breast Cancer

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Treatment (PDQ®)–Patient Version General Information About Breast Cancer Go to Health Professional Version Key Points Breast ...

  11. The multifaceted mechanism of Leptin signaling within tumor microenvironment in driving breast cancer growth and progression.

    Directory of Open Access Journals (Sweden)

    Sebastiano eAndò

    2014-11-01

    Full Text Available Adipokines represent likely candidates to mediate the increased breast cancer risk and the enhanced progression associated with obesity. Other contributors to obesity-related cancer progression are insulin/IGF-1 pathways and hormones. Among these, the adipokine leptin is the most intensively studied in both metabolism in general and in cancer due to the fact that leptin levels increase in proportion of fat mass. Leptin is primarily synthesized from adipocytes, but it is also produced by other cells including fibroblasts. In this latter case, it has been well demonstrated how cancer-associated fibroblasts express leptin receptor and secrete leptin which sustains a short autocrine loop and is able to target tumor epithelial cells enhancing breast cancer cell motility and invasiveness. In addition, it has been reported that leptin may induce breast cancer to undergo a transition from epithelial to spindle-like mesenchymal morphology, activating the signaling pathways devoted to the EMT. Thus, it emerges how leptin may play a crucial role in mediating malignant cell and tumor microenvironment interactions. Here, we present an overview of the role of leptin in breast cancer, covering the following topics: 1 leptin as an amplifier of estrogen signaling in tumor epithelial cells contributing to the promotion of carcinogenesis; 2 leptin as a crucial player in mediating tumor-stroma interaction and influencing EMT-linked mechanisms, that may sustain breast cancer growth and progression; 3 leptin and leptin receptor targeting as novel therapeutic strategies for breast cancer treatment.

  12. Frondoside A inhibits human breast cancer cell survival, migration, invasion and the growth of breast tumor xenografts.

    Science.gov (United States)

    Al Marzouqi, Nadia; Iratni, Rabah; Nemmar, Abderrahim; Arafat, Kholoud; Ahmed Al Sultan, Mahmood; Yasin, Javed; Collin, Peter; Mester, Jan; Adrian, Thomas E; Attoub, Samir

    2011-10-01

    Breast cancer is a major challenge for pharmacologists to develop new drugs to improve the survival of cancer patients. Frondoside A is a triterpenoid glycoside isolated from the sea cucumber, Cucumaria frondosa. It has been demonstrated that Frondoside A inhibited the growth of pancreatic cancer cells in vitro and in vivo. We investigated the impact of Frondoside A on human breast cancer cell survival, migration and invasion in vitro, and on tumor growth in nude mice, using the human estrogen receptor-negative breast cancer cell line MDA-MB-231. The non-tumorigenic MCF10-A cell line derived from normal human mammary epithelium was used as control. Frondoside A (0.01-5 μM) decreased the viability of breast cancer cells in a concentration- and time-dependent manner, with 50%-effective concentration (EC50) of 2.5 μM at 24h. MCF10-A cells were more resistant to the cytotoxic effect of Frondoside A (EC50 superior to 5 μM at 24 h). In the MDA-MB-231 cells, Frondoside A effectively increased the sub-G1 (apoptotic) cell fraction through the activation of p53, and subsequently the caspases 9 and 3/7 cell death pathways. In addition, Frondoside A induced a concentration-dependent inhibition of MDA-MB-231 cell migration and invasion. In vivo, Frondoside A (100 μg/kg/dayi.p. for 24 days) strongly decreased the growth of MDA-MB-231 tumor xenografts in athymic mice, without manifest toxic side-effects. Moreover, we found that Frondoside A could enhance the killing of breast cancer cells induced by the chemotherapeutic agent paclitaxel. These findings identify Frondoside A as a promising novel therapeutic agent for breast cancer. PMID:21741966

  13. Breast cancer

    International Nuclear Information System (INIS)

    More than 20-year follow-up of A-bomb survivors in Hiroshima and Nagasaki has a crucial role in determining the relationship of radiation to the occurrence of breast cancer. In 1967, Wanebo et al have first reported 27 cases of breast cancer during the period 1950-1966 among the Adult Health Study population of A-bomb survivors. Since then, follow-up surveys for breast cancer have been made using the Life Span Study (LSS) cohort, and the incidence of breast cancer has increased year by year; that is breast cancer was identified in 231 cases by the first LSS series (1950-1969), 360 cases by the second LSS series (1950-1974), 564 cases by the third LSS series (1950-1980), and 816 cases in the fourth LSS series (1950-1085). The third LSS series have revealed a high risk for radiation-induced breast cancer in women aged 10 or less at the time of exposure (ATE). Both relative and absolute risks are found to be decreased with increasing ages ATE. Based on the above-mentioned findings and other studies on persons exposed medical radiation, radiation-induced breast cancer is characterized by the following: (1) the incidence of breast cancer is linearly increased with increasing radiation doses; (2) both relative and absolute risks for breast cancer are high in younger persons ATE; (3) age distribution of breast cancer in proximally exposed A-bomb survivors is the same as that in both distally A-bomb survivors and non-exposed persons, and there is no difference in histology between the former and latter groups. Thus, immature mammary gland cells before the age of puberty are found to be most radiosensitive. (N.K.)

  14. Breast Cancer: Treatment Options

    Science.gov (United States)

    ... 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 ...

  15. Ganoderma lucidum (Reishi) Inhibits Cancer Cell Growth and Expression of Key Molecules in Inflammatory Breast Cancer

    OpenAIRE

    Martínez-Montemayor, Michelle M; Acevedo, Raysa Rosario; Otero-Franqui, Elisa; Cubano, Luis A.; Suranganie F. Dharmawardhane

    2011-01-01

    Inflammatory breast cancer (IBC) is the most lethal and least understood form of advanced breast cancer. Its lethality originates from its nature of invading the lymphatic system and absence of a palpable tumor mass. Different from other metastatic breast cancer cells, IBC cells invade by forming tumor spheroids that retain E-cadherin-based cell–cell adhesions. Herein we describe the potential of the medicinal mushroom Ganoderma lucidum (Reishi) as an attractive candidate for anti-IBC therapy...

  16. Transforming growth factor-β and breast cancer: Transforming growth factor-β/SMAD signaling defects and cancer

    International Nuclear Information System (INIS)

    Transforming growth factor-β (TGF-β) is a tumor suppressor, the function of which is compromised in many types of human cancer, including breast cancer. The tumor suppressive effects of TGF-β are caused by potent inhibition of cell proliferation due to cell cycle arrest in the G1 phase. Such antiproliferative responses are mediated by a signaling system that includes two types of cell surface receptors and intracellular signal transducers, the SMAD proteins. Different molecular mechanisms can lead to loss of antiproliferative TGF-β responses in tumor cells, including mutations in components of the signaling system and inhibition of the SMAD signaling pathway by aberrant activities of various regulatory molecules. Some of these mechanisms will be discussed, with emphasis on their potential involvement in breast tumorigenesis

  17. Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a german breast group 26/breast international group 03-05 study

    DEFF Research Database (Denmark)

    von Minckwitz, Gunter; du Bois, Andreas; Schmidt, Marcus;

    2009-01-01

    : Patients with HER-2-positive breast cancer that progresses during treatment with trastuzumab were randomly assigned to receive capecitabine (2,500 mg/m(2) body-surface area on days 1 through 14 [1,250 mg/m(2) semi-daily]) alone or with continuation of trastuzumab (6 mg/kg body weight) in 3-week cycles. The...... not associated with increased toxicity. CONCLUSION: Continuation of trastuzumab plus capecitabine showed a significant improvement in overall response and time to progression compared with capecitabine alone in women with HER-2-positive breast cancer who experienced progression during trastuzumab......PURPOSE: Trastuzumab shows clinical activity in human epidermal growth factor receptor 2 (HER-2)-positive early and advanced breast cancer. In the German Breast Group 26/Breast International Group 03-05 trial, we investigated if trastuzumab treatment should be continued beyond progression. METHODS...

  18. Breast cancer

    CERN Multimedia

    2002-01-01

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

  19. Gene expression signature in organized and growth arrested mammaryacini predicts good outcome in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fournier, Marcia V.; Martin, Katherine J.; Kenny, Paraic A.; Xhaja, Kris; Bosch, Irene; Yaswen, Paul; Bissell, Mina J.

    2006-02-08

    To understand how non-malignant human mammary epithelial cells (HMEC) transit from a disorganized proliferating to an organized growth arrested state, and to relate this process to the changes that occur in breast cancer, we studied gene expression changes in non-malignant HMEC grown in three-dimensional cultures, and in a previously published panel of microarray data for 295 breast cancer samples. We hypothesized that the gene expression pattern of organized and growth arrested mammary acini would share similarities with breast tumors with good prognoses. Using Affymetrix HG-U133A microarrays, we analyzed the expression of 22,283 gene transcripts in two HMEC cell lines, 184 (finite life span) and HMT3522 S1 (immortal non-malignant), on successive days post-seeding in a laminin-rich extracellular matrix assay. Both HMECs underwent growth arrest in G0/G1 and differentiated into polarized acini between days 5 and 7. We identified gene expression changes with the same temporal pattern in both lines. We show that genes that are significantly lower in the organized, growth arrested HMEC than in their proliferating counterparts can be used to classify breast cancer patients into poor and good prognosis groups with high accuracy. This study represents a novel unsupervised approach to identifying breast cancer markers that may be of use clinically.

  20. Functional proteomic analysis reveals the involvement of KIAA1199 in breast cancer growth, motility and invasiveness

    International Nuclear Information System (INIS)

    KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness. We validated the previous microarray observation by tissue microarray immunohistochemistry using a TMA slide containing 12 breast tumor tissue cores and 12 corresponding normal tissues. We performed the shRNA-mediated knockdown of KIAA1199 in MDA-MB-231 and HS578T cells to study the role of this protein in cell proliferation, migration and apoptosis in vitro. We studied the effects of KIAA1199 knockdown in vivo in two groups of mice (n = 5). We carried out the SILAC LC-MS/MS based proteomic studies on the involvement of KIAA1199 in breast cancer. KIAA1199 mRNA and protein was significantly overexpressed in breast tumor specimens and cell lines as compared with non-neoplastic breast tissues from large-scale microarray and studies of breast cancer cell lines and tumors. To gain deeper insights into the novel role of KIAA1199 in breast cancer, we modulated KIAA1199 expression using shRNA-mediated knockdown in two breast cancer cell lines (MDA-MB-231 and HS578T), expressing higher levels of KIAA1199. The KIAA1199 knockdown cells showed reduced motility and cell proliferation in vitro. Moreover, when the knockdown cells were injected into the mammary fat pads of female athymic nude mice, there was a significant decrease in tumor incidence and growth. In addition, quantitative proteomic analysis revealed that knockdown of KIAA1199 in breast cancer (MDA-MB-231) cells affected a broad range of cellular functions including apoptosis, metabolism and cell motility. Our findings indicate that KIAA1199 may play an important role in breast tumor growth and invasiveness, and that it

  1. Endothelial cells stimulate growth of normal and cancerous breast epithelial cells in 3D culture

    Directory of Open Access Journals (Sweden)

    Magnusson Magnus K

    2010-07-01

    Full Text Available Abstract Background Epithelial-stromal interaction provides regulatory signals that maintain correct histoarchitecture and homeostasis in the normal breast and facilitates tumor progression in breast cancer. However, research on the regulatory role of the endothelial component in the normal and malignant breast gland has largely been neglected. The aim of the study was to investigate the effects of endothelial cells on growth and differentiation of human breast epithelial cells in a three-dimensional (3D co-culture assay. Methods Breast luminal and myoepithelial cells and endothelial cells were isolated from reduction mammoplasties. Primary cells and established normal and malignant breast cell lines were embedded in reconstituted basement membrane in direct co-culture with endothelial cells and by separation of Transwell filters. Morphogenic and phenotypic profiles of co-cultures was evaluated by phase contrast microscopy, immunostaining and confocal microscopy. Results In co-culture, endothelial cells stimulate proliferation of both luminal- and myoepithelial cells. Furthermore, endothelial cells induce a subpopulation of luminal epithelial cells to form large acini/ducts with a large and clear lumen. Endothelial cells also stimulate growth and cloning efficiency of normal and malignant breast epithelial cell lines. Transwell and gradient co-culture studies show that endothelial derived effects are mediated - at least partially - by soluble factors. Conclusion Breast endothelial cells - beside their role in transporting nutrients and oxygen to tissues - are vital component of the epithelial microenvironment in the breast and provide proliferative signals to the normal and malignant breast epithelium. These growth promoting effects of endothelial cells should be taken into consideration in breast cancer biology.

  2. The time-evolution of DCIS size distributions with applications to breast cancer growth and progression

    OpenAIRE

    Dowty, James G.; Byrnes, Graham B; Gertig, Dorota M

    2013-01-01

    Ductal carcinoma {\\em in situ} (DCIS) lesions are non-invasive tumours of the breast which are thought to precede most invasive breast cancers (IBC). As individual DCIS lesions are initiated, grow and invade (i.e. become IBC) the size distribution of the DCIS lesions present in a given human population will evolve. We derive a differential equation governing this evolution and show, for given assumptions about growth and invasion, that there is a unique distribution which does not vary with t...

  3. Breast Cancer

    Science.gov (United States)

    ... click the brackets in the lower right-hand corner of the video screen. To reduce the videos, ... with breast cancer are under way. With early detection, and prompt and appropriate treatment, the outlook for ...

  4. Breast cancer

    International Nuclear Information System (INIS)

    This article is about the diagnosis, treatment and monitoring of breast cancer. Positive diagnosis is based on clinical mammary exam, mammography, mammary ultrasonography, and histological study. Before the chemotherapy and radiotherapy treatment are evaluated the risks

  5. Surgery for Breast Cancer

    Science.gov (United States)

    ... Next Topic Breast-conserving surgery (lumpectomy) Surgery for breast cancer Most women with breast cancer have some type ... Relieve symptoms of advanced cancer Surgery to remove breast cancer There are two main types of surgery to ...

  6. Learning about Breast Cancer

    Science.gov (United States)

    ... 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, ...

  7. Protein disulfide isomerases in the endoplasmic reticulum promote anchorage-independent growth of breast cancer cells.

    Science.gov (United States)

    Wise, Randi; Duhachek-Muggy, Sara; Qi, Yue; Zolkiewski, Michal; Zolkiewska, Anna

    2016-06-01

    Metastatic breast cancer cells are exposed to stress of detachment from the extracellular matrix (ECM). Cultured breast cancer cells that survive this stress and are capable of anchorage-independent proliferation form mammospheres. The purpose of this study was to explore a link between mammosphere growth, ECM gene expression, and the protein quality control system in the endoplasmic reticulum (ER). We compared the mRNA and protein levels of ER folding factors in SUM159PT and MCF10DCIS.com breast cancer cells grown as mammospheres versus adherent conditions. Publicly available gene expression data for mammospheres formed by primary breast cancer cells and for circulating tumor cells (CTCs) were analyzed to assess the status of ECM/ER folding factor genes in clinically relevant samples. Knock-down of selected protein disulfide isomerase (PDI) family members was performed to examine their roles in SUM159PT mammosphere growth. We found that cells grown as mammospheres had elevated expression of ECM genes and ER folding quality control genes. CTC gene expression data for an index patient indicated that upregulation of ECM and ER folding factor genes occurred at the time of acquired therapy resistance and disease progression. Knock-down of PDI, ERp44, or ERp57, three members of the PDI family with elevated protein levels in mammospheres, in SUM159PT cells partially inhibited the mammosphere growth. Thus, breast cancer cell survival and growth under detachment conditions require enhanced assistance of the ER protein folding machinery. Targeting ER folding factors, in particular members of the PDI family, may improve the therapeutic outcomes in metastatic breast cancer. PMID:27161215

  8. Examining breast cancer growth and lifestyle risk factors: early life, childhood, and adolescence.

    Science.gov (United States)

    Ruder, Elizabeth H; Dorgan, Joanne F; Kranz, Sibylle; Kris-Etherton, Penny M; Hartman, Terryl J

    2008-08-01

    The perinatal period, childhood, and adolescence are important intervals for breast cancer risk development. Endogenous estrogen exposure is thought to be highest in utero, and exposure to estrogens throughout life plays an important role in increasing breast cancer risk. Some evidence suggests that breast tissue is not fully differentiated until after the first full-term pregnancy; thus, breast tissue might be more susceptible to carcinogenic influences during early life and adolescence. Birth characteristics of the daughter, including gestational age, birth weight, and birth length are associated with maternal hormone levels during the index pregnancy, and birth size has been related to daughter's timing of puberty and adult breast cancer incidence. Furthermore, early life and adolescence are critical times for maturation of the hypothalamic pituitary ovarian axis, which regulates production of ovarian hormones including estrogen and progesterone. Childhood height, growth, diet, and body mass index (BMI) have also been associated with breast cancer risk later in life. Of the examined characteristics, we conclude that the available evidence is suggestive of a positive relationship of breast cancer risk with birth weight, birth length, and adolescent height, and an inverse relationship with gestational age and childhood BMI, although several inconsistencies exist in the literature. The best evidence for a relationship of adolescent diet and adult breast cancer risk is indirect, and the relationship of diet, weight status, and weight gain in childhood deserves further attention. The interaction of birth characteristics with established risk factors over the life course, such as age at menarche, in addition to gene-environment interactions, require more research. Further study is also needed to clarify the biologic mechanisms influencing the observed associations. PMID:18757260

  9. Role for chondroitin sulfate glycosaminoglycan in NEDD9-mediated breast cancer cell growth

    NARCIS (Netherlands)

    Iida, J.; Dorchak, J.; Clancy, R.; Slavik, J.; Ellsworth, R.; Katagiri, Y.; Pugacheva, E.N.; Kuppevelt, T.H. van; Mural, R.J.; Cutler, M.L.; Shriver, C.D.

    2015-01-01

    There are lines of evidence demonstrating that NEDD9 (Cas-L, HEF-1) plays a key role in the development, progression, and metastasis of breast cancer cells. We previously reported that NEDD9 plays a critical role for promoting migration and growth of MDA-MB-231. In order to further characterize the

  10. Desacetyl nimbinene inhibits breast cancer growth and metastasis through reactive oxygen species mediated mechanisms.

    Science.gov (United States)

    Arumugam, Arunkumar; Subramani, Ramadevi; Nandy, Sushmita; Powell, Sara; Velazquez, Marissa; Orozco, Alexis; Galvez, Adriana; Lakshmanaswamy, Rajkumar

    2016-05-01

    Accumulation of reactive oxygen species (ROS) has been implicated in induction of apoptosis and regulation of key signaling molecules in cancer cells. Phytochemicals are potent source of anticancer drugs as wells as potential inducers of ROS. Neem (Azadirachta indica) is a medicinal plant used for the treatment of various diseases. The main objective of this study is to investigate the anticancer effect of desacetyl nimbinene (DAN; an active ingredient of neem) against breast cancer. Normal and breast cancer cell lines were used for the study. The effect of DAN on cell proliferation, apoptosis, ROS generation, migration, and invasion was analyzed. Antioxidant enzymes superoxide dismutase (SOD)1 and SOD2 were overexpressed to test the effect of DAN-induced ROS generation on breast cancer growth. Key survival and apoptotic protein markers were analyzed to validate the anticancer effect of DAN. Our data demonstrated that DAN inhibited the growth of breast cancer cells by inducing ROS generation. Further investigations revealed that DAN treatment lead to the loss of mitochondrial membrane potential resulting in mitochondria-dependent apoptotic cell death. Increased phosphorylation of c-Jun-N-terminal kinase (JNK) and reduced phosphorylation of p38 were also observed in response to DAN treatment. Inhibition of ROS production by overexpressing antioxidant enzymes SOD1 and SOD2 reduced the DAN-induced cytotoxicity. Additionally, DAN significantly inhibited migration and invasion of MDA-MB-231 breast cancer cells. Overall, our data suggest that DAN exerts its anticancer effect on breast cancer by induction of mitochondria-mediated apoptosis mediated by ROS accumulation. PMID:26637227

  11. Effects of lycopene on the insulin-like growth factor (IGF) system in premenopausal breast cancer survivors and women at high familial breast cancer risk

    NARCIS (Netherlands)

    Voskuil, Dorien W.; Vrieling, Alina; Korse, Catharina M.; Beijnen, Jos H.; Bonfrer, Johannes M. G.; van Doorn, Jaap; Kaas, Reinie; Oldenburg, Hester S. A.; Russell, Nicola S.; Rutgers, Emiel J. T.; Verhoef, Senno; van Leeuwen, Flora E.; van't Veer, Laura J.; Rookus, Matti A.

    2008-01-01

    Insulin-like growth factor-I (IGF-I) is an important growth factor associated with increased risk of premenopausal breast cancer. We conducted a randomized, placebo-controlled, double-blind, crossover trial to evaluate whether tomato-derived lycopene supplementation (30 mg/day for 2 mo) decreases se

  12. The roles of support seeking and race/ethnicity in posttraumatic growth among breast cancer survivors

    OpenAIRE

    Kent, Erin E.; Alfano, Catherine M.; Smith, Ashley Wilder; Bernstein, Leslie; McTiernan, Anne; Baumgartner, Kathy B.; Ballard-Barbash, Rachel

    2013-01-01

    Posttraumatic growth (PTG) after cancer can minimize the emotional impact of disease and treatment; however, the facilitators of PTG, including support-seeking, are unclear. We examined the role of support-seeking on PTG among 604 breast cancer survivors ages 40–64 from the Health Eating, Activity, and Lifestyle (HEAL) Study. Multivariable linear regression was used to examine predictors of support-seeking (participation in support groups and confiding in healthcare providers) as well as the ...

  13. Puerariae radix isoflavones and their metabolites inhibit growth and induce apoptosis in breast cancer cells

    International Nuclear Information System (INIS)

    Puerariae radix (PR) is a popular natural herb and a traditional food in Asia, which has antithrombotic and anti-allergic properties and stimulates estrogenic activity. In the present study, we investigated the effects of the PR isoflavones puerarin, daidzein, and genistein on the growth of breast cancer cells. Our data revealed that after treatment with PR isoflavones, a dose-dependent inhibition of cell growth occurred in HS578T, MDA-MB-231, and MCF-7 cell lines. Results from cell cycle distribution and apoptosis assays revealed that PR isoflavones induced cell apoptosis through a caspase-3-dependent pathway and mediated cell cycle arrest in the G2/M phase. Furthermore, we observed that the serum metabolites of PR (daidzein sulfates/glucuronides) inhibited proliferation of the breast cancer cells at a 50% cell growth inhibition (GI50) concentration of 2.35 μM. These results indicate that the daidzein constituent of PR can be metabolized to daidzein sulfates or daidzein glucuronides that exhibit anticancer activities. The protein expression levels of the active forms of caspase-9 and Bax in breast cancer cells were significantly increased by treatment with PR metabolites. These metabolites also increased the protein expression levels of p53 and p21. We therefore suggest that PR may act as a chemopreventive and/or chemotherapeutic agent against breast cancer by reducing cell viability and inducing apoptosis.

  14. Relaxins enhance growth of spontaneous murine breast cancers as well as metastatic colonization of the brain.

    Science.gov (United States)

    Binder, Claudia; Chuang, Eugenia; Habla, Christina; Bleckmann, Annalen; Schulz, Matthias; Bathgate, Ross; Einspanier, Almuth

    2014-01-01

    Relaxins are known for their tissue remodeling capacity which is also a hallmark of cancer progression. However, their role in the latter context is still unclear, particularly in breast cancer. In a mouse model with spontaneously arising breast cancer due to erbB2-overexpression we show that exposure to porcine relaxin results in significantly enhanced tumour growth as compared to control animals. This is accompanied by increased serum concentrations of progesterone and estradiol as well as elevated expression of the respective receptors and the relaxin receptor RXFP1 in the tumour tissue. It is also associated with enhanced infiltration by tumour-associated macrophages which are known to promote tumour progression. Additionally, we show in an ex vivo model of metastatic brain colonization that porcine relaxin as well as human brain-specific relaxin-3 promotes invasion into the brain tissue and enhance interaction of breast cancer cells with the resident brain macrophages, the microglia. Relaxin signaling is mediated via RXFP1, since R 3/I5, a specific agonist of the relaxin-3 receptor RXFP3 in the brain, does not significantly enhance invasion. Taken together, these findings strongly support a role of relaxins in the progression of breast cancer where they foster primary tumour growth as well as metastatic colonization by direct and indirect means. PMID:23963762

  15. Relaxin reduces xenograft tumour growth of human MDA-MB-231 breast cancer cells

    OpenAIRE

    Radestock, Yvonne; Hoang-Vu, Cuong; Hombach-Klonisch, Sabine

    2008-01-01

    Introduction Relaxin levels are increased in cases of human breast cancer and has been shown to promote cancer cell migration in carcinoma cells of the breast, prostate gland and thyroid gland. In oestrogen receptor alpha-negative MDA-MB-231 human breast cancer cells, relaxin was shown to down-regulate the metastasis-promoting protein S100A4 (metastasin), a highly significant prognostic factor for poor survival in breast cancer patients. The cellular mechanisms of relaxin exposure in breast c...

  16. The subcellular localization of IGFBP5 affects its cell growth and migration functions in breast cancer

    Directory of Open Access Journals (Sweden)

    Sahin Aysegul

    2009-04-01

    Full Text Available Abstract Background Insulin-like growth factor binding protein 5 (IGFBP5 has been shown to be associated with breast cancer metastasis in clinical marker studies. However, a major difficulty in understanding how IGFBP5 functions in this capacity is the paradoxical observation that ectopic overexpression of IGFBP5 in breast cancer cell lines results in suppressed cellular proliferation. In cancer tissues, IGFBP5 resides mainly in the cytoplasm; however, in transfected cells, IGFBP5 is mainly located in the nucleus. We hypothesized that subcellular localization of IGFBP5 affects its functions in host cells. Methods To test this hypothesis, we generated wild-type and mutant IGFBP5 expression constructs. The mutation occurs within the nuclear localization sequence (NLS of the protein and is generated by site-directed mutagenesis using the wild-type IGFBP5 expression construct as a template. Next, we transfected each expression construct into MDA-MB-435 breast cancer cells to establish stable clones overexpressing either wild-type or mutant IGFBP5. Results Functional analysis revealed that cells overexpressing wild-type IGFBP5 had significantly lower cell growth rate and motility than the vector-transfected cells, whereas cells overexpressing mutant IGFBP5 demonstrated a significantly higher ability to proliferate and migrate. To illustrate the subcellular localization of the proteins, we generated wild-type and mutant IGFBP5-pDsRed fluorescence fusion constructs. Fluorescence microscopy imaging revealed that mutation of the NLS in IGFBP5 switched the accumulation of IGFBP5 from the nucleus to the cytoplasm of the protein. Conclusion Together, these findings imply that the mutant form of IGFBP5 increases proliferation and motility of breast cancer cells and that mutation of the NLS in IGFBP5 results in localization of IGFBP5 in the cytoplasm, suggesting that subcellular localization of IGFBP5 affects its cell growth and migration functions in the

  17. Covalent Targeting of Fibroblast Growth Factor Receptor Inhibits Metastatic Breast Cancer.

    Science.gov (United States)

    Brown, Wells S; Tan, Li; Smith, Andrew; Gray, Nathanael S; Wendt, Michael K

    2016-09-01

    Therapeutic targeting of late-stage breast cancer is limited by an inadequate understanding of how tumor cell signaling evolves during metastatic progression and by the currently available small molecule inhibitors capable of targeting these processes. Herein, we demonstrate that both β3 integrin and fibroblast growth factor receptor-1 (FGFR1) are part of an epithelial-mesenchymal transition (EMT) program that is required to facilitate metastatic outgrowth in response to fibroblast growth factor-2 (FGF2). Mechanistically, β3 integrin physically disrupts an interaction between FGFR1 and E-cadherin, leading to a dramatic redistribution of FGFR1 subcellular localization, enhanced FGF2 signaling and increased three-dimensional (3D) outgrowth of metastatic breast cancer cells. This ability of β3 integrin to drive FGFR signaling requires the enzymatic activity of focal adhesion kinase (FAK). Consistent with these mechanistic data, we demonstrate that FGFR, β3 integrin, and FAK constitute a molecular signature capable of predicting decreased survival of patients with the basal-like subtype of breast cancer. Importantly, covalent targeting of a conserved cysteine in the P-loop of FGFR1-4 with our newly developed small molecule, FIIN-4, more effectively blocks 3D metastatic outgrowth as compared with currently available FGFR inhibitors. In vivo application of FIIN-4 potently inhibited the growth of metastatic, patient-derived breast cancer xenografts and murine-derived metastases growing within the pulmonary microenvironment. Overall, the current studies demonstrate that FGFR1 works in concert with other EMT effector molecules to drive aberrant downstream signaling, and that these events can be effectively targeted using our novel therapeutics for the treatment of the most aggressive forms of breast cancer. Mol Cancer Ther; 15(9); 2096-106. ©2016 AACR. PMID:27371729

  18. Damaged DNA binding protein 2 plays a role in breast cancer cell growth.

    Directory of Open Access Journals (Sweden)

    Zilal Kattan

    Full Text Available The Damaged DNA binding protein 2 (DDB2, is involved in nucleotide excision repair as well as in other biological processes in normal cells, including transcription and cell cycle regulation. Loss of DDB2 function may be related to tumor susceptibility. However, hypothesis of this study was that DDB2 could play a role in breast cancer cell growth, resulting in its well known interaction with the proliferative marker E2F1 in breast neoplasia. DDB2 gene was overexpressed in estrogen receptor (ER-positive (MCF-7 and T47D, but not in ER-negative breast cancer (MDA-MB231 and SKBR3 or normal mammary epithelial cell lines. In addition, DDB2 expression was significantly (3.0-fold higher in ER-positive than in ER-negative tumor samples (P = 0.0208 from 16 patients with breast carcinoma. Knockdown of DDB2 by small interfering RNA in MCF-7 cells caused a decrease in cancer cell growth and colony formation. Inversely, introduction of the DDB2 gene into MDA-MB231 cells stimulated growth and colony formation. Cell cycle distribution and 5 Bromodeoxyuridine incorporation by flow cytometry analysis showed that the growth-inhibiting effect of DDB2 knockdown was the consequence of a delayed G1/S transition and a slowed progression through the S phase of MCF-7 cells. These results were supported by a strong decrease in the expression of S phase markers (Proliferating Cell Nuclear Antigen, cyclin E and dihydrofolate reductase. These findings demonstrate for the first time that DDB2 can play a role as oncogene and may become a promising candidate as a predictive marker in breast cancer.

  19. Breast Cancer -- Male

    Science.gov (United States)

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

  20. The effect of menopause and hysterectomy on systemic vascular endothelial growth factor in women undergoing surgery for breast cancer

    International Nuclear Information System (INIS)

    Vascular endothelial growth factor (VEGF) is a potent angiogenic cytokine produced physiologically by the uterus. Pathological secretion by tumours promotes growth and metastasis. High circulating VEGF levels potentially have a deleterious effect on breast cancer by promoting disease progression. The aims of this study were to investigate circulating VEGF levels in breast cancer patients and assess the effect of menopause or hysterectomy on systemic VEGF. Patients undergoing primary surgery for breast cancer and controls matched for age, menopausal and hysterectomy status were prospectively recruited. Serum VEGF, FSH, LH, estrogen, progesterone and platelet levels were measured. Serum VEGF was corrected for platelet load (sVEGFp) to provide a biologically relevant measurement of circulating VEGF. SVEGFp levels were analyzed with respect to tumor characteristics, menopausal status and hysterectomy status. Two hundred women were included in the study; 89 breast cancer patients and 111 controls. SVEGFp levels were significantly higher in breast cancer patients compared to controls (p = 0.0001), but were not associated with clinico-pathological tumor characteristics. Systemic VEGF levels reduced significantly in the breast cancer patients following tumor excision (p = 0.018). The highest systemic VEGF levels were observed in postmenopausal breast cancer patients. Postmenopausal women who had had a previous hysterectomy had significantly higher VEGF levels than those with an intact postmenopausal uterus (p = 0.001). This study identifies an intact postmenopausal uterus as a potential means of reducing circulating levels of VEGF which could confer a protective effect against breast cancer metastatic potential

  1. Tyrosine kinase signalling in breast cancer: Fibroblast growth factors and their receptors

    International Nuclear Information System (INIS)

    The fibroblast growth factors [Fgfs (murine), FGFs (human)] constitute a large family of ligands that signal through a class of cell-surface tyrosine kinase receptors. Fgf signalling has been associated in vitro with cellular differentiation as well as mitogenic and motogenic responses. In vivo, Fgfs are critical for animal development, and some have potent angiogenic properties. Several Fgfs have been identified as oncogenes in murine mammary cancer, where their deregulation is associated with proviral insertions of the mouse mammary tumour virus (MMTV). Thus, in some mammary tumours of MMTV-infected mouse strains, integration of viral genomic DNA into the somatic DNA of mammary epithelial cells was found to have caused the inappropriate expression of members of this family of growth factors. Although examination of human breast cancers has shown an altered expression of FGFs or of their receptors in some tumours, their role in the causation of breast disease is unclear and remains controversial

  2. GDC-0941 and Cisplatin in Treating Patients With Androgen Receptor-Negative Triple Negative Metastatic Breast Cancer

    Science.gov (United States)

    2015-08-17

    Estrogen Receptor Negative Breast Cancer; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Triple Negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer

  3. ING1 and 5-Azacytidine Act Synergistically to Block Breast Cancer Cell Growth

    OpenAIRE

    Satbir Thakur; Xiaolan Feng; Zhong Qiao Shi; Amudha Ganapathy; Manoj Kumar Mishra; Peter Atadja; Don Morris; Karl Riabowol

    2012-01-01

    BACKGROUND: Inhibitor of Growth (ING) proteins are epigenetic "readers" that recognize trimethylated lysine 4 of histone H3 (H3K4Me3) and target histone acetyl transferase (HAT) and histone deacetylase (HDAC) complexes to chromatin. METHODS AND PRINCIPAL FINDINGS: Here we asked whether dysregulating two epigenetic pathways with chemical inhibitors showed synergistic effects on breast cancer cell line killing. We also tested whether ING1 could synergize better with chemotherapeutics that targe...

  4. Anti-tissue factor short hairpin RNA inhibits breast cancer growth in vivo

    OpenAIRE

    Bluff, J. E.; Amarzguioui, M.; Slattery, J; Reed, M.W.R.; Brown, N J; Staton, C A

    2010-01-01

    Abstract In breast cancer, there is a correlation between tissue factor (TF) expression, angiogenesis and disease progression. TF stimulates tumour angiogenesis, in part, through up-regulation of vascular endothelial growth factor (VEGF). Therefore, this study aimed to establish whether TF stimulates angiogenesis and tumour progression directly and independent of VEGF up-regulation. Initially, the effects of TF and VEGF were assessed on endothelial cell migration (Boyden chamber) a...

  5. Emodin Inhibits Breast Cancer Growth by Blocking the Tumor-Promoting Feedforward Loop between Cancer Cells and Macrophages.

    Science.gov (United States)

    Iwanowycz, Stephen; Wang, Junfeng; Hodge, Johnie; Wang, Yuzhen; Yu, Fang; Fan, Daping

    2016-08-01

    Macrophage infiltration correlates with severity in many types of cancer. Tumor cells recruit macrophages and educate them to adopt an M2-like phenotype through the secretion of chemokines and growth factors, such as MCP1 and CSF1. Macrophages in turn promote tumor growth through supporting angiogenesis, suppressing antitumor immunity, modulating extracellular matrix remodeling, and promoting tumor cell migration. Thus, tumor cells and macrophages interact to create a feedforward loop supporting tumor growth and metastasis. In this study, we tested the ability of emodin, a Chinese herb-derived compound, to inhibit breast cancer growth in mice and examined the underlying mechanisms. Emodin was used to treat mice bearing EO771 or 4T1 breast tumors. It was shown that emodin attenuated tumor growth by inhibiting macrophage infiltration and M2-like polarization, accompanied by increased T-cell activation and reduced angiogenesis in tumors. The tumor inhibitory effects of emodin were lost in tumor-bearing mice with macrophage depletion. Emodin inhibited IRF4, STAT6, and C/EBPβ signaling and increased inhibitory histone H3 lysine 27 tri-methylation (H3K27m3) on the promoters of M2-related genes in tumor-associated macrophages. In addition, emodin inhibited tumor cell secretion of MCP1 and CSF1, as well as expression of surface anchoring molecule Thy-1, thus suppressing macrophage migration toward and adhesion to tumor cells. These results suggest that emodin acts on both breast cancer cells and macrophages and effectively blocks the tumor-promoting feedforward loop between the two cell types, thereby inhibiting breast cancer growth and metastasis. Mol Cancer Ther; 15(8); 1931-42. ©2016 AACR. PMID:27196773

  6. Palbociclib in Combination With Tamoxifen as First Line Therapy for Metastatic Hormone Receptor Positive Breast Cancer

    Science.gov (United States)

    2016-07-05

    Hormone Receptor Positive Malignant Neoplasm of Breast; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Estrogen Receptor Positive Breast Cancer; Progesterone Receptor Positive Tumor; Metastatic Breast Cancer

  7. Breast Cancer Overview

    Science.gov (United States)

    ... Other less common types of breast cancer include: Medullary Mucinous Tubular Metaplastic Papillary breast cancer Inflammatory breast cancer is a faster-growing type of cancer that accounts for about 1% to 5% of all breast cancers. Paget’s disease is a type of cancer that begins in ...

  8. Breast cancer screenings

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000837.htm Breast cancer screenings To use the sharing features on this page, please enable JavaScript. Breast cancer screenings can help find breast cancer early, before ...

  9. Male Breast Cancer

    Science.gov (United States)

    Although breast cancer is much more common in women, men can get it too. It happens most often to men between ... 60 and 70. Breast lumps usually aren't cancer. However, most men with breast cancer have lumps. ...

  10. Male Breast Cancer

    Science.gov (United States)

    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 ...

  11. Inhibition of insulin-like growth factor-1 receptor signaling enhances growth-inhibitory and proapoptotic effects of gefitinib (Iressa) in human breast cancer cells

    OpenAIRE

    Camirand, Anne; Zakikhani, Mahvash; Young, Fiona; Pollak, Michael

    2005-01-01

    Introduction Gefitinib (Iressa, ZD 1839, AstraZeneca) blocks the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) and inhibits proliferation of several human cancer cell types including breast cancer. Phase II clinical trials with gefitinib monotherapy showed an objective response of 9 to 19% in non-small-cell lung cancer patients and less than 10% for breast cancer, and phase III results have indicated no benefit of gefitinib in combination with chemotherapy over chemo...

  12. Wwox suppresses breast cancer cell growth through modulation of the hedgehog–GLI1 signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Anwen [Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai (China); Wei, Li [Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai (China); Department of Oncology, NO. 401 hospital of PLA, Qingdao, Shandong (China); Ying, Mingzhen; Wu, Hongmei; Hua, Jin [Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai (China); Wang, Yajie, E-mail: yajiewang@live.com [Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai (China)

    2014-01-24

    Highlights: • We investigated Gli1 as a novel partner of Wwox. • We observed a physical association between Wwox and the Gli1. • Wwox–Gli1 interaction affects Gli1 intracellular localization. • Gli1 Blocks Wwox-induced growth inhibition and apoptosis in T47D cells. - Abstract: Wwox is a tumor suppressor that is frequently deleted or altered in several cancer types, including breast cancer. Previous studies have shown that ectopic expression of Wwox inhibits proliferation of breast cancer cells. However, the underlying mechanism remains unclear. To better understand the molecular mechanisms of Wwox function, we investigated novel partners of this protein. Utilizing the coimmunoprecipitation assay, we observed a physical association between Wwox and the Gli1 zinc-finger transcription factor involved in the hedgehog pathway. Our results further demonstrated that Wwox expression triggered redistribution of nuclear Gli1 to the cytoplasm. Additionally, ectopic expression of Wwox reduced Gli1 expression in vitro. Furthermore, Gli1 Blocks Wwox-induced breast cancer cell growth inhibition. These findings suggest a functional crosstalk between Wwox and hedgehog–GLI1 signaling pathway in tumorigenesis.

  13. Targeting an IKBKE cytokine network impairs triple-negative breast cancer growth.

    Science.gov (United States)

    Barbie, Thanh U; Alexe, Gabriela; Aref, Amir R; Li, Shunqiang; Zhu, Zehua; Zhang, Xiuli; Imamura, Yu; Thai, Tran C; Huang, Ying; Bowden, Michaela; Herndon, John; Cohoon, Travis J; Fleming, Timothy; Tamayo, Pablo; Mesirov, Jill P; Ogino, Shuji; Wong, Kwok-Kin; Ellis, Matthew J; Hahn, William C; Barbie, David A; Gillanders, William E

    2014-12-01

    Triple-negative breast cancers (TNBCs) are a heterogeneous set of cancers that are defined by the absence of hormone receptor expression and HER2 amplification. Here, we found that inducible IκB kinase-related (IKK-related) kinase IKBKE expression and JAK/STAT pathway activation compose a cytokine signaling network in the immune-activated subset of TNBC. We found that treatment of cultured IKBKE-driven breast cancer cells with CYT387, a potent inhibitor of TBK1/IKBKE and JAK signaling, impairs proliferation, while inhibition of JAK alone does not. CYT387 treatment inhibited activation of both NF-κB and STAT and disrupted expression of the protumorigenic cytokines CCL5 and IL-6 in these IKBKE-driven breast cancer cells. Moreover, in 3D culture models, the addition of CCL5 and IL-6 to the media not only promoted tumor spheroid dispersal but also stimulated proliferation and migration of endothelial cells. Interruption of cytokine signaling by CYT387 in vivo impaired the growth of an IKBKE-driven TNBC cell line and patient-derived xenografts (PDXs). A combination of CYT387 therapy with a MEK inhibitor was particularly effective, abrogating tumor growth and angiogenesis in an aggressive PDX model of TNBC. Together, these findings reveal that IKBKE-associated cytokine signaling promotes tumorigenicity of immune-driven TNBC and identify a potential therapeutic strategy using clinically available compounds. PMID:25365225

  14. Clonogenic growth of human breast cancer cells co-cultured in direct contact with serum-activated fibroblasts

    International Nuclear Information System (INIS)

    Accumulating evidence suggests that fibroblasts play a pivotal role in promoting the growth of breast cancer cells. The objective of the present study was to characterize and validate an in vitro model of the interaction between small numbers of human breast cancer cells and human fibroblasts. We measured the clonogenic growth of small numbers of human breast cancer cells co-cultured in direct contact with serum-activated, normal human fibroblasts. Using DNA microarrays, we also characterized the gene expression profile of the serum-activated fibroblasts. In order to validate the in vivo relevance of our experiments, we then analyzed clinical samples of metastatic breast cancer for the presence of myofibroblasts expressing α-smooth muscle actin. Clonogenic growth of human breast cancer cells obtained directly from in situ and invasive tumors was dramatically and consistently enhanced when the tumor cells were co-cultured in direct contact with serum-activated fibroblasts. This effect was abolished when the cells were co-cultured in transwells separated by permeable inserts. The fibroblasts in our experimental model exhibited a gene expression signature characteristic of 'serum response' (i.e. myofibroblasts). Immunostaining of human samples of metastatic breast cancer tissue confirmed that myofibroblasts are in direct contact with breast cancer cells. Serum-activated fibroblasts promote the clonogenic growth of human breast cancer cells in vitro through a mechanism that involves direct physical contact between the cells. This model shares many important molecular and phenotypic similarities with the fibroblasts that are naturally found in breast cancers

  15. Opioid growth factor receptor (OGFR expression is downregulated with progression of triple negative breast cancer

    Directory of Open Access Journals (Sweden)

    Beth Worley

    2015-12-01

    Full Text Available Purpose: Triple negative breast cancer (TNBC is an aggressive form of breast cancer that accounts for approximately 15% of the newly diagnosed cancers worldwide, and disproportionately affects younger women and women of color. Although many forms of breast cancer are successfully treated, new therapies are needed for TNBC. A novel regulatory system, the opioid growth factor (OGF – opioid growth factor receptor (OGFr axis, plays a determining role in neoplasia. OGF is an endogenous peptide that binds specifically to OGFr to inhibit cell replication. As some human cancers grow, OGFr expression is diminished, thus limiting the therapeutic efficacy of OGF. The OGF-OGFr axis is present in human TNBC cell line MDA-MB-231 and OGF  inhibits cell replication in a dosage-related, receptor-mediated manner. Methods: The present study investigated whether OGFr protein expression in human breast cancer cell lines grown in vitro or transplanted into nude mice, changed with the stage of proliferation or size of tumor using western blotting, semi-quantitative immunohistochemistry, and DNA synthesis techniques. Results: Comparison of log and confluent TNBC cultures revealed that OGF expression was significantly decreased in confluent cultures relative to levels in log-phase cells. Western blot analyses confirmed that OGFr was reduced in confluent TNBC and MCF-7 breast cancer cells in comparison to corresponding log-phase cells. Moreover, BrdU labeling was reduced in confluent cells. Small (<500 mm3 and large (>1000 mm3 TNBC tumors grown in nude mice were processed for semiquantitative   measurement of OGF and OGFr. The expression of both peptide and receptor in large tumors was downregulated relative to small tumors. Conclusion: The reduced expression of the inhibitory peptide and receptor diminishes the efficacy of the OGF-OGFr axis as a biotherapy. These data suggest that the OGF-OGFr pathway is altered with cancer progression and one or more elements of

  16. Hispolon inhibits the growth of estrogen receptor positive human breast cancer cells through modulation of estrogen receptor alpha

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Eun Hyang; Jang, Soon Young; Cho, In-Hye [Department of Pharmacy, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701 (Korea, Republic of); Hong, Darong [Department of Life and Nanopharmaceutical Science, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701 (Korea, Republic of); Jung, Bom; Park, Min-Ju [Department of Pharmacy, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701 (Korea, Republic of); Kim, Jong-Ho, E-mail: jonghokim@khu.ac.kr [Department of Pharmacy, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701 (Korea, Republic of)

    2015-08-07

    Human estrogen receptor α (ERα) is a nuclear transcription factor that is a major therapeutic target in breast cancer. The transcriptional activity of ERα is regulated by certain estrogen-receptor modulators. Hispolon, isolated from Phellinus linteus, a traditional medicinal mushroom called Sanghwang in Korea, has been used to treat various pathologies, such as inflammation, gastroenteric disorders, lymphatic diseases, and cancers. In this latter context, Hispolon has been reported to exhibit therapeutic efficacy against various cancer cells, including melanoma, leukemia, hepatocarcinoma, bladder cancer, and gastric cancer cells. However, ERα regulation by Hispolon has not been reported. In this study, we investigated the effects of Hispolon on the growth of breast cancer cells. We found that Hispolon decreased expression of ERα at both mRNA and the protein levels in MCF7 and T47D human breast cancer cells. Luciferase reporter assays showed that Hispolon decreased the transcriptional activity of ERα. Hispolon treatment also inhibited expression of the ERα target gene pS2. We propose that Hispolon, an anticancer drug extracted from natural sources, inhibits cell growth through modulation of ERα in estrogen-positive breast cancer cells and is a candidate for use in human breast cancer chemotherapy. - Highlights: • Hispolon decreased ERα expression at both mRNA and protein levels. • Hispolon decreased ERα transcriptional activity. • Hispolon treatment inhibited expression of ERα target gene pS2. • Shikonin is a candidate chemotherapeutic target in the treatment of human breast cancer.

  17. Hispolon inhibits the growth of estrogen receptor positive human breast cancer cells through modulation of estrogen receptor alpha

    International Nuclear Information System (INIS)

    Human estrogen receptor α (ERα) is a nuclear transcription factor that is a major therapeutic target in breast cancer. The transcriptional activity of ERα is regulated by certain estrogen-receptor modulators. Hispolon, isolated from Phellinus linteus, a traditional medicinal mushroom called Sanghwang in Korea, has been used to treat various pathologies, such as inflammation, gastroenteric disorders, lymphatic diseases, and cancers. In this latter context, Hispolon has been reported to exhibit therapeutic efficacy against various cancer cells, including melanoma, leukemia, hepatocarcinoma, bladder cancer, and gastric cancer cells. However, ERα regulation by Hispolon has not been reported. In this study, we investigated the effects of Hispolon on the growth of breast cancer cells. We found that Hispolon decreased expression of ERα at both mRNA and the protein levels in MCF7 and T47D human breast cancer cells. Luciferase reporter assays showed that Hispolon decreased the transcriptional activity of ERα. Hispolon treatment also inhibited expression of the ERα target gene pS2. We propose that Hispolon, an anticancer drug extracted from natural sources, inhibits cell growth through modulation of ERα in estrogen-positive breast cancer cells and is a candidate for use in human breast cancer chemotherapy. - Highlights: • Hispolon decreased ERα expression at both mRNA and protein levels. • Hispolon decreased ERα transcriptional activity. • Hispolon treatment inhibited expression of ERα target gene pS2. • Shikonin is a candidate chemotherapeutic target in the treatment of human breast cancer

  18. Novel STAT3 phosphorylation inhibitors exhibit potent growth suppressive activity in pancreatic and breast cancer cells

    Science.gov (United States)

    Lin, Li; Hutzen, Brian; Zuo, Mingxin; Ball, Sarah; Deangelis, Stephanie; Foust, Elizabeth; Pandit, Bulbul; Ihnat, Michael A.; Shenoy, Satyendra S.; Kulp, Samuel; Li, Pui-Kai; Li, Chenglong; Fuchs, James; Lin, Jiayuh

    2010-01-01

    The constitutive activation of Signal Transducer and Activator of Transcription 3 (STAT3) is frequently detected in most types of human cancer where it plays important roles in survival, drug-resistance, angiogenesis, and other functions. Targeting constitutive STAT3 signaling is thus an attractive therapeutic approach for these cancers. We have recently developed novel small molecule STAT3 inhibitors known as FLLL31 and FLLL32, which are derived from curcumin (the primary bioactive compound of turmeric). These compounds are designed to bind selectively to Janus Kinase 2 (JAK2) and the STAT3 SH2 domain, which serves crucial roles in STAT3 dimerization and signal transduction. Here we show that FLLL31 and FLLL32 are effective inhibitors of STAT3 phosphorylation, DNA binding activity, and transactivation in vitro, leading to the impediment of multiple oncogenic processes and the induction of apoptosis in pancreatic and breast cancer cell lines. FLLL31 and FLLL32 also inhibit colony formation in soft agar, cell invasion, and exhibit synergy with the anti-cancer drug doxorubicin against breast cancer cells. In addition, we show that FLLL32 can inhibit the induction of STAT3 phosphorylation by Interferon-α (IFNα) and Interleukin-6 (IL-6) in breast cancer cells. We also demonstrate that administration of FLLL32 can inhibit tumor growth and vascularity in chicken embryo xenografts as well as substantially reduce tumor volumes in mouse xenografts. Our findings highlight the potential of these new compounds and their efficacy in targeting pancreatic and breast cancers that exhibit constitutive STAT3 signaling. PMID:20215512

  19. Over expression of vascular endothelial growth factor in correlation to Ki-67, grade and stage of breast cancer

    International Nuclear Information System (INIS)

    Objective was to assess the significance of vascular endothelial growth factor (VEGF) protein over expression in human breast cancer, and its possible correlation with cell proliferation marker (Ki-67), grade and stage of breast cancer. We carried out this study at the Department of Pathology, Kufa University, between November 2006 and September 2007. A retrospective study was employed on paraffin-embedded blocks from 52 female patients with breast cancer. A group of 21 patients with benign breast lesions was included for comparison and 14 cases of normal breast tissue as control group. The investigation designed to employ immunohistochemistry using Avidin-Biotin Complex (ABC) method for detection of both VEGF and Ki-67. A total of 87 samples were included. Vascular endothelial growth factor immunoexpression was considered as positive in 61.5% of malignant and in 19% of benign breast lesions. No over expression sign has been noticed in normal breast tissue (p<0.005). No significant difference in VEGF over expression among different histological types of breast cancer (p<0.05). Vascular endothelial growth factor immunostaining was positively correlated with Ki-67, grade, stage, lymph node metastasis, and recurrence of breast cancer (p<0.05).No such correlation has been seen when the age of the patients has been considered. Vascular endothelial growth factor plays an important role in the pathogenesis of breast cancer evolution and supports the evidence of its role in angiogenesis and cell survival. This study recommended that the blocking of VEGF may be target for blocking angiogenesis and hence improving the efficacy of anti-cancer therapy. (author)

  20. Suppression of cell growth and invasion by miR-205 in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Hailong Wu; Shoumin Zhu; Yin-Yuan Mo

    2009-01-01

    MicroRNAs (miRNAs) are endogenous, small, non-coding RNAs, which are capable of silencing gene expression at the post-transcriptional level. In this study, we report that miR-205 is significantly underexpressed in breast tumor compared to the matched normal breast tissue. Similarly, breast cancer cell lines, including MCF-7 and MDA-MB-231, express a lower level miR-205 than the non-malignant MCF-10A cells. Of interest, ectopic expression of miR-205 significantly inhibits cell proliferation and anchorage independent growth, as well as cell invasion. Furthermore, miR-205 was shown to suppress lung metastasis in an animal model. Finally, western blot combined with the luciferase reporter assays demonstrate that ErbB3 and vascular endothelial growth factor A (VEGF-A) are direct targets for miR-205, and this miR-205-mediated suppression is likely through the direct interaction with the putative miR-205 binding site in the 3'-untranslated region (3'-UTR) of ErbB3 and VEGF-A. Together, these results suggest that miR-205 is a tumor suppressor in breast cancer.

  1. Transforming growth factor-β and breast cancer: Lessons learned from genetically altered mouse models

    International Nuclear Information System (INIS)

    Transforming growth factor (TGF)-βs are plausible candidate tumor suppressors in the breast. They also have oncogenic activities under certain circumstances, however. Genetically altered mouse models provide powerful tools to analyze the complexities of TGF-βaction in the context of the whole animal. Overexpression of TGF-β can suppress tumorigenesis in the mammary gland, raising the possibility that use of pharmacologic agents to enhance TGF-β function locally might be an effective method for the chemoprevention of breast cancer. Conversely, loss of TGF-β response increases spontaneous and induced tumorigenesis in the mammary gland. This confirms that endogenous TGF-βs have tumor suppressor activity in the mammary gland, and suggests that the loss of TGF-β receptors seen in some human breast hyperplasias may play a causal role in tumor development

  2. Early breast cancer

    International Nuclear Information System (INIS)

    The therapy of early breast cancer has been changing during the last decennium. It requires a multi-disciplinary approach and in each of these disciplines improvements have been implemented. The result is that treatment schedules can now be adapted to specific subgroups. In this review early breast cancer is defined as operable disease, using the criteria set out by Haagensen. Emphasis is given to describing the new developments in prognostic criteria, since these form the basis for creating subgroups for specific treatment schedules. Distinction is made between the factors relating to growth rate and those relating to metastatic potential. Data on screening promises a beneficial effect of the implementation of screening in national health care programs. Important shifts are seen in treatment schedules; the place of postoperative radiotherapy after classic ablative treatment is being challenged, whereas it plays a major role in the new breast conserving therapy schedules. The data mentioned in the review suggest that a large proportion of 'operable' cases can be treated with breast conservation but details in the technique of breast conserving therapy are still under investigation. They form a major part of the coming prospective studies in breast cancer. Improvements in reconstruction techniques, creating better cosmetic results, make reconstruction more competitive with breast conserving therapy. The use of chemotherapy and endocrine manipulation in early breast cancer has now been clearly confirmed by the overview technique by the Peto-group, thanks to all efforts of individual trialists together. (orig.)

  3. SL-01, an oral derivative of gemcitabine, inhibited human breast cancer growth through induction of apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuan-Yuan; Qin, Yi-Zhuo; Wang, Rui-Qi [Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan 250012 (China); Li, Wen-Bao, E-mail: wbli92128@yahoo.com [Sanlugen PharmaTech, Rm 506, No. 2766 Yingxiu Road, Jinan 250101 (China); Qu, Xian-Jun, E-mail: qxj@sdu.edu.cn [Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan 250012 (China)

    2013-08-23

    Highlights: •SL-01 is an oral derivative of gemcitabine. •SL-01 possessed activity against human breast cancer growth via apoptotic induction. •SL-01’s activity was more potently than that of gemcitabine. •SL-01 inhibited cancer growth without toxicity to mice. -- Abstract: SL-01 is an oral derivative of gemcitabine that was synthesized by introducing the moiety of 3-(dodecyloxycarbonyl) pyrazine-2-carbonyl at N4-position on cytidine ring of gemcitabine. We aimed to evaluate the efficacy of SL-01 on human breast cancer growth. SL-01 significantly inhibited MCF-7 proliferation as estimated by colorimetric assay. Flow cytometry assay indicated the apoptotic induction and cell cycle arrest in G1 phase. SL-01 modulated the expressions of p-ATM, p53 and p21 and decrease of cyclin D1 in MCF-7 cells. Further experiments were performed in a MCF-7 xenografts mouse model. SL-01 by oral administration strongly inhibited MCF-7 xenografts growth. This effect of SL-01 might arise from its roles in the induction of apoptosis. Immunohistochemistry assay showed the increase of TUNEL staining cells. Western blotting indicated the modulation of apoptotic proteins in SL-01-treated xenografts. During the course of study, there was no evidence of toxicity to mice. In contrast, the decrease of neutrophil cells in peripheral and increase of AST and ALT levels in serum were observed in the gemcitabine-treated mice. Conclusion: SL-01 possessed similar activity against human breast cancer growth with gemcitabine, whereas, with lower toxicity to gemcitabine. SL-01 is a potent oral agent that may supplant the use of gemcitabine.

  4. SL-01, an oral derivative of gemcitabine, inhibited human breast cancer growth through induction of apoptosis

    International Nuclear Information System (INIS)

    Highlights: •SL-01 is an oral derivative of gemcitabine. •SL-01 possessed activity against human breast cancer growth via apoptotic induction. •SL-01’s activity was more potently than that of gemcitabine. •SL-01 inhibited cancer growth without toxicity to mice. -- Abstract: SL-01 is an oral derivative of gemcitabine that was synthesized by introducing the moiety of 3-(dodecyloxycarbonyl) pyrazine-2-carbonyl at N4-position on cytidine ring of gemcitabine. We aimed to evaluate the efficacy of SL-01 on human breast cancer growth. SL-01 significantly inhibited MCF-7 proliferation as estimated by colorimetric assay. Flow cytometry assay indicated the apoptotic induction and cell cycle arrest in G1 phase. SL-01 modulated the expressions of p-ATM, p53 and p21 and decrease of cyclin D1 in MCF-7 cells. Further experiments were performed in a MCF-7 xenografts mouse model. SL-01 by oral administration strongly inhibited MCF-7 xenografts growth. This effect of SL-01 might arise from its roles in the induction of apoptosis. Immunohistochemistry assay showed the increase of TUNEL staining cells. Western blotting indicated the modulation of apoptotic proteins in SL-01-treated xenografts. During the course of study, there was no evidence of toxicity to mice. In contrast, the decrease of neutrophil cells in peripheral and increase of AST and ALT levels in serum were observed in the gemcitabine-treated mice. Conclusion: SL-01 possessed similar activity against human breast cancer growth with gemcitabine, whereas, with lower toxicity to gemcitabine. SL-01 is a potent oral agent that may supplant the use of gemcitabine

  5. Synthesis and secretion of platelet-derived growth factor by human breast cancer cell lines

    International Nuclear Information System (INIS)

    The authors report that human breast cancer cells secrete a growth factor that is biologically and immunologically similar to platelet-derived growth factor (PDGF). Serum-free medium conditioned by estrogen-independent MDA-MB-231 or estrogen-dependent MCF-7 cells contains a mitogenic or competence activity that is capable of inducing incorporation of [3H] thymidine into quiescent Swiss 3T3 cells in the presence of platelet-poor plasma. Like authentic PDGF, the PDGF-like activity produced by breast cancer cells is stable after acid and heat treatment (950C) and inhibited by reducing agents. The mitogenic activity comigrates with a material of ≅30 kDa on NaDodSO4/polyacrylamide gels. Immunoprecipitation with PDGF antiserum of proteins from metabolically labeled cell lysates and conditioned medium followed by analysis on nonreducing NaDodSO4/polyacrylamide gels identified proteins of 30 and 34 kDa. Upon reduction, the 30- and 34-kDa bands were converted to 15- and 16-kDa bands suggesting that the immunoprecipitated proteins were made up of two disulfide-linked polypeptides similar to PDGF. Hybridization studies with cDNA probes for the A chain PDGF and the B chain of PDGF/SIS identified transcripts for both PDGF chains in the MCF-7 and MDA-MB-231 cells. The data summarized above provide conclusive evidence for the synthesis and hormonally regulated secretion of a PDGF-like mitogen by breast carcinoma cells. Production of a PDGF-like growth factor by breast cancer cell lines may be important in mediating paracrine stimulation of tumor growth

  6. Ganoderma lucidum (Reishi) inhibits cancer cell growth and expression of key molecules in inflammatory breast cancer.

    Science.gov (United States)

    Martínez-Montemayor, Michelle M; Acevedo, Raysa Rosario; Otero-Franqui, Elisa; Cubano, Luis A; Dharmawardhane, Suranganie F

    2011-01-01

    Inflammatory breast cancer (IBC) is the most lethal and least understood form of advanced breast cancer. Its lethality originates from its nature of invading the lymphatic system and absence of a palpable tumor mass. Different from other metastatic breast cancer cells, IBC cells invade by forming tumor spheroids that retain E-cadherin-based cell-cell adhesions. Herein we describe the potential of the medicinal mushroom Ganoderma lucidum (Reishi) as an attractive candidate for anti-IBC therapy. Reishi contains biological compounds that are cytotoxic against cancer cells. We report the effects of Reishi on viability, apoptosis, invasion, and its mechanism of action in IBC cells (SUM-149). Results show that Reishi selectively inhibits cancer cell viability although it does not affect the viability of noncancerous mammary epithelial cells. Apoptosis induction is consistent with decreased cell viability. Reishi inhibits cell invasion and disrupts the cell spheroids that are characteristic of the IBC invasive pathology. Reishi decreases the expression of genes involved in cancer cell survival and proliferation (BCL-2, TERT, PDGFB), and invasion and metastasis (MMP-9), whereas it increases the expression of IL8. Reishi reduces BCL-2, BCL-XL, E-cadherin, eIF4G, p120-catenin, and c-Myc protein expression and gelatinase activity. These findings suggest that Reishi is an effective anti-IBC therapeutic. PMID:21888505

  7. Biomimetic apatite-coated porous PVA scaffolds promote the growth of breast cancer cells

    International Nuclear Information System (INIS)

    Recapitulating the native environment of bone tissue is essential to develop in vitro models of breast cancer bone metastasis. The bone is a composite material consisting of organic matrix and inorganic mineral phase, primarily hydroxyapatite. In this study, we report the mineralization of porous poly vinyl alcohol (PVA) scaffolds upon incubation in modified Hanks' Balanced Salt Solution (HBSS) for 14 days. Scanning electron microscopy, energy dispersive X-ray analysis, and X-ray diffraction analysis revealed that the deposited minerals have composition similar to hydroxyapatite. The study demonstrated that the rate of nucleation and growth of minerals was faster on surfaces of less porous scaffolds. However, upon prolonged incubation, formation of mineral layer was observed on the surface of all the scaffolds. In addition, the study also demonstrated that 3D mineralization only occurred for scaffolds with highly interconnected porous networks. The mineralization of the scaffolds promoted the adsorption of serum proteins and consequently, the adhesion and proliferation of breast cancer cells. - Highlights: • Porous PVA scaffolds fabricated via mechanical agitation followed by freeze-drying. • Mineralization of the scaffold was carried out by utilizing biomimetic approach. • Mineralization resulted in increased protein adsorption on the scaffold. • Increased breast cancer cell growth was observed on mineralized scaffolds

  8. Biomimetic apatite-coated porous PVA scaffolds promote the growth of breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Ye, Mao; Mohanty, Pravansu; Ghosh, Gargi, E-mail: gargi@umich.edu

    2014-11-01

    Recapitulating the native environment of bone tissue is essential to develop in vitro models of breast cancer bone metastasis. The bone is a composite material consisting of organic matrix and inorganic mineral phase, primarily hydroxyapatite. In this study, we report the mineralization of porous poly vinyl alcohol (PVA) scaffolds upon incubation in modified Hanks' Balanced Salt Solution (HBSS) for 14 days. Scanning electron microscopy, energy dispersive X-ray analysis, and X-ray diffraction analysis revealed that the deposited minerals have composition similar to hydroxyapatite. The study demonstrated that the rate of nucleation and growth of minerals was faster on surfaces of less porous scaffolds. However, upon prolonged incubation, formation of mineral layer was observed on the surface of all the scaffolds. In addition, the study also demonstrated that 3D mineralization only occurred for scaffolds with highly interconnected porous networks. The mineralization of the scaffolds promoted the adsorption of serum proteins and consequently, the adhesion and proliferation of breast cancer cells. - Highlights: • Porous PVA scaffolds fabricated via mechanical agitation followed by freeze-drying. • Mineralization of the scaffold was carried out by utilizing biomimetic approach. • Mineralization resulted in increased protein adsorption on the scaffold. • Increased breast cancer cell growth was observed on mineralized scaffolds.

  9. Gain of glucose-independent growth upon metastasis of breast cancer cells to the brain

    OpenAIRE

    Chen, Jinyu; Lee, Ho-Jeong; Wu, Xuefeng; Huo, Lei; Kim, Sun-Jin; Xu, Lei; Wang, Yan; He, Junqing; Bollu, Lakshmi Reddy; Gao, Guang; Su, Fei; Briggs, James; Liu, Xiaojing; Melman, Tamar; Asara, John M.

    2014-01-01

    Breast cancer brain metastasis is resistant to therapy and a particularly poor prognostic feature in patient survival. Altered metabolism is a common feature of cancer cells but little is known as to what metabolic changes benefit breast cancer brain metastases. We found that brain-metastatic breast cancer cells evolved the ability to survive and proliferate independent of glucose due to enhanced gluconeogenesis and oxidations of glutamine and branched chain amino acids, which together sustai...

  10. Insulin-like growth factor-1 enhances mortality risk in women with breast cancer through epithelial-mesenchymal transition initiation

    Directory of Open Access Journals (Sweden)

    Ala-Eddin Al Moustafa

    2013-01-01

    Full Text Available The metastatic disease which leads to cancer patients′ mortality results from a multi-step process of tumor progression caused by gene alteration and cooperation. Accordingly, it was recently demonstrated that alteration level of insulin-like growth factor-1 (IGF-1 and IGF binding protein-3 (IGFBP-3 are associated with the risk of cancer related death in several human malignancies including breast cancer. On the other hand, epithelial-mesenchymal transition (EMT is described as a crucial event in cancer progression and metastasis. Herein, we discuss the association between IGF-1, IGF-1/IGFBP-3 ratio, EMT, and breast cancer mortality.

  11. Phosphatase PTP4A3 Promotes Triple-Negative Breast Cancer Growth and Predicts Poor Patient Survival.

    Science.gov (United States)

    den Hollander, Petra; Rawls, Kathryn; Tsimelzon, Anna; Shepherd, Jonathan; Mazumdar, Abhijit; Hill, Jamal; Fuqua, Suzanne A W; Chang, Jenny C; Osborne, C Kent; Hilsenbeck, Susan G; Mills, Gordon B; Brown, Powel H

    2016-04-01

    Triple-negative breast cancer (TNBC) has the worst prognosis of all breast cancers, and women diagnosed with TNBC currently lack targeted treatment options. To identify novel targets for TNBC, we evaluated phosphatase expression in breast tumors and characterized their contributions to in vitro and in vivo growth of TNBC. Using Affymetrix microarray analysis of 102 breast cancers, we identified 146 phosphatases that were significantly differentially expressed in TNBC compared with estrogen receptor (ER)-positive tumors. Of these, 19 phosphatases were upregulated (0.66-fold; FDR = 0.05) in TNBC compared with ER-positive breast cancers. We knocked down 17 overexpressed phosphatases in four triple-negative and four ER-positive breast cancer lines using specific siRNAs and found that depletion of six of these phosphatases significantly reduced growth and anchorage-independent growth of TNBC cells to a greater extent than ER-positive cell lines. Further analysis of the phosphatase PTP4A3 (also known as PRL-3) demonstrated its requirement for G1-S cell-cycle progression in all breast cancer cells, but PTP4A3 regulated apoptosis selectively in TNBC cells. In addition, PTP4A3 inhibition reduced the growth of TNBC tumors in vivo Moreover, in silico analysis revealed the PTP4A3 gene to be amplified in 29% of basal-like breast cancers, and high expression of PTP4A3 could serve as an independent prognostic indicator for worse overall survival. Collectively, these studies define the importance of phosphatase overexpression in TNBC and lay the foundation for the development of new targeted therapies directed against phosphatases or their respective signaling pathways for TNBC patients. Cancer Res; 76(7); 1942-53. ©2016 AACR. PMID:26921331

  12. Modulation of estrogen and epidermal growth factor receptors by rosemary extract in breast cancer cells.

    Science.gov (United States)

    González-Vallinas, Margarita; Molina, Susana; Vicente, Gonzalo; Sánchez-Martínez, Ruth; Vargas, Teodoro; García-Risco, Mónica R; Fornari, Tiziana; Reglero, Guillermo; Ramírez de Molina, Ana

    2014-06-01

    Breast cancer is the leading cause of cancer-related mortality among females worldwide, and therefore the development of new therapeutic approaches is still needed. Rosemary (Rosmarinus officinalis L.) extract possesses antitumor properties against tumor cells from several organs, including breast. However, in order to apply it as a complementary therapeutic agent in breast cancer, more information is needed regarding the sensitivity of the different breast tumor subtypes and its effect in combination with the currently used chemotherapy. Here, we analyzed the antitumor activities of a supercritical fluid rosemary extract (SFRE) in different breast cancer cells, and used a genomic approach to explore its effect on the modulation of ER-α and HER2 signaling pathways, the most important mitogen pathways related to breast cancer progression. We found that SFRE exerts antitumor activity against breast cancer cells from different tumor subtypes and the downregulation of ER-α and HER2 receptors by SFRE might be involved in its antitumor effect against estrogen-dependent (ER+) and HER2 overexpressing (HER2+) breast cancer subtypes. Moreover, SFRE significantly enhanced the effect of breast cancer chemotherapy (tamoxifen, trastuzumab, and paclitaxel). Overall, our results support the potential utility of SFRE as a complementary approach in breast cancer therapy. PMID:24615943

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Wei [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Chai, Hongyan [Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Li, Ying; Zhao, Haixia; Xie, Xianfei; Zheng, Hao; Wang, Chenlong; Wang, Xue [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Yang, Guifang [Department of Pathology, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Cai, Xiaojun [Department of Ophthalmology, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Falck, John R. [Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390 (United States); Yang, Jing, E-mail: yangjingliu@yahoo.com.cn [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    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

  15. Breast Cancer Disparities

    Science.gov (United States)

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

  16. Insulin-like growth factor binding protein 2 is a marker for antiestrogen resistant human breast cancer cell lines but is not a major growth regulator

    DEFF Research Database (Denmark)

    Juncker-Jensen, A; Lykkesfeldt, A E; Worm, J;

    2006-01-01

    Antiestrogens target the estrogen receptor and counteract the growth stimulatory action of estrogen on human breast cancer. However, acquired resistance to antiestrogens is a major clinical problem in endocrine treatment of breast cancer patients. To mimic acquired resistance, we have used a mode...... resistant cell growth was observed. Thus, we were able to establish IGFBP-2 as a marker for antiestrogen resistant breast cancer cell lines, although IGFBP-2 was not a major contributor to the resistant cell growth.......Antiestrogens target the estrogen receptor and counteract the growth stimulatory action of estrogen on human breast cancer. However, acquired resistance to antiestrogens is a major clinical problem in endocrine treatment of breast cancer patients. To mimic acquired resistance, we have used a model...... system with the antiestrogen sensitive human breast cancer cell line MCF-7 and several antiestrogen resistant cell lines derived from the parental MCF-7 cell line. This model system was used to study the expression and possible involvement in resistant cell growth of insulin-like growth factor binding...

  17. Factors affecting disease-free survival in patients with human epidermal growth factor receptor 2-positive breast cancer who receive adjuvant trastuzumab

    OpenAIRE

    GÜNDÜZ, SEYDA; GÖKSU, SEMA SEZGIN; Arslan, Deniz; TATLI, ALI MURAT; Uysal, Mükremin; GÜNDÜZ, UMUT RIZA; SEVINÇ, MERT MAHSUNI; COŞKUN, HASAN SENOL; BOZCUK, Hakan; MUTLU, HASAN; Savas, Burhan

    2015-01-01

    Breast cancer is the most frequently diagnosed cancer in women worldwide and the second cause of cancer-related mortality. A total of 20–30% of patients with early-stage breast cancer develop recurrence within the first 5 years following diagnosis. Trastuzumab significantly improves overall survival and disease-free survival (DFS) in women with human epidermal growth factor receptor 2 (HER2)-positive early and locally advanced breast cancer. This study aimed to determine the factors that affe...

  18. Breast cancer

    International Nuclear Information System (INIS)

    This book contains outstanding papers presented at the 3rd International Copenhagen Symposium on Detection of Breast Cancer, 1985. The Symposium was an opportunity to learn from extensive screening procedures carried out at outstanding centers in the United States, Sweden, the Netherlands, and England. Furthermore, the symposium dealt with new modalities such as ultrasonography, magnification techniques, and magnetic resonance; and very important contributions concerning self-examination, fine needle aspiration biopsy, and radiation risks were presented. A whole section was also dedicated to the highly important cooperation between radiologist, surgeon, and pathologist. (orig./MG)

  19. Growth suppression and radiosensitivity increase by HMGB1 in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Yang JIAO; Hai-chao WANG; Sai-jun FAN

    2007-01-01

    Aim: HMGB 1 (high-mobility group box-1) is a nuclear protein containing a con- sensus RB (retinoblastoma)-binding LXCXE motif. In this study, we studied the potential association of HMGB 1 and RB and the in vitro and in vivo activities of HMGB 1 in human breast cancer cells. Methods: The protein-protein interaction was determined by immunoprecipitation-Western blotting and glutathione-S-trans- ferase capture assays; cell growth and radiosensitivity were examined by cell counts, MTT assay, and clonogenic assay; cell cycle progression and apoptosis were evaluated using flow cytometry; and the antitumor activity of HMGB 1 was examined with tumor xenografts in nude mice. Results: HMGB 1 was associated with RB via a LXCXE motif-dependent mechanism. HMGB 1 enhanced the ability of RB for E2F and cyclin A transcription repression. The increased expression of HMGB 1 conferred an altered phenotypes characterized by the suppression of cell growth; G12 arrest and apoptosis was induced in MCF-7 cells containing the wild- type retinoblastoma (Rb) gene, but showed no activities in BT-549 cells contain- ing the Rb gene deletion. The HMGB 1-induced apoptosis accompanied by caspase 3 activation and PARP (poly(ADP-ribose)polymerase) cleavage. HMGB 1 elevated the radiosensitivity of breast cancer cells in both the MCF-7 and BT-549 cell lines. The enhanced expression of HMGB 1 caused a suppression of growth of MCF-7 tumor xenografts in nude mice, while LXCXE-defective HMGB 1 completely lost antitumor growth activity. Conclusion: HMGB 1 functions as a tumor suppressor and radiosensitizer in breast cancer. A HMGB 1-RB interaction is critical for the HMGB1-mediated transcriptional repression, cell growth inhibition, G12 cell cycle arrest, apoptosis induction, and tumor growth suppression, but is not required for radiosensitization. Therefore, it may be possible to design new therapies for the treatment of breast cancer that exert their effects by modulating the HMGB 1 and RB regulatory

  20. Breast cancer in men

    Science.gov (United States)

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

  1. Small interfering RNA targeted to secretory clusterin blocks tumor growth, motility, and invasion in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Zhaohe Niu; Xinhui Li; Bin Hu; Rong Li; Ligang Wang; Lilin Wu; Xingang Wang

    2012-01-01

    Clusterin/apolipoprotein J (Clu) is a ubiquitously expressed secreted heterodimeric glycoprotein that is implicated in several physiological processes.It has been reported that the elevated level of secreted clusterin (sClu) protein is associated with poor survival in breast cancer patients and can induce metastasis in rodent models.In this study,we investigated the effects of sClu inhibition with small interfering RNAs (siRNAs) on cell motility,invasion,and growth in vitro and in vivo.MDA-MB-231 cells were transfected with pSuper-siRNA/sClu.Cell survival and proliferation were examined by 3-(4,5-dimethyl-thiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and clonogenic survival assay.The results showed that sClu silencing significantly inhibited the proliferation of MDA-MB-231 cells.The invasion and migration ability were also dramatically decreased,which was detected by matrigel assays.TUNEL staining and caspase-3 activity assay demonstrated that sClu silencing also could increase the apoptosis rate of cells,resulting in the inhibition of cell growth.We also determined the effects of sClu silencing on tumor growth and metastatic progression in an orthotopic breast cancer model.The results showed that orthotopic primary tumors derived from MDA-MB-231/pSuper sClu siRNA cells grew significantly slower than tumors derived from parental MDA-MB-231 or MDA-MB-231/pSuper scramble siRNA cells,and metastasize less to the lungs.These data suggest that secretory clusterin plays a significant role in tumor growth and metastatic progression.Knocking-down sClu gene expression may provide a valuable method for breast cancer therapy.

  2. Alphavirus replicon particles containing the gene for HER2/neu inhibit breast cancer growth and tumorigenesis

    International Nuclear Information System (INIS)

    Overexpression of the HER2/neu gene in breast cancer is associated with an increased incidence of metastatic disease and with a poor prognosis. Although passive immunotherapy with the humanized monoclonal antibody trastuzumab (Herceptin) has shown some effect, a vaccine capable of inducing T-cell and humoral immunity could be more effective. Virus-like replicon particles (VRP) of Venezuelan equine encephalitis virus containing the gene for HER2/neu (VRP-neu) were tested by an active immunotherapeutic approach in tumor prevention models and in a metastasis prevention model. VRP-neu prevented or significantly inhibited the growth of HER2/neu-expressing murine breast cancer cells injected either into mammary tissue or intravenously. Vaccination with VRP-neu completely prevented tumor formation in and death of MMTV-c-neu transgenic mice, and resulted in high levels of neu-specific CD8+ T lymphocytes and serum IgG. On the basis of these findings, clinical testing of this vaccine in patients with HER2/neu+ breast cancer is warranted

  3. Premenopausal Obesity and Breast Cancer Growth Rates in a Rodent Model.

    Science.gov (United States)

    Matthews, Shawna B; McGinley, John N; Neil, Elizabeth S; Thompson, Henry J

    2016-01-01

    Obese premenopausal women with breast cancer have poorer prognosis for long term survival, in part because their tumors are larger at the time of diagnosis than are found in normal weight women. Whether larger tumor mass is due to obesity-related barriers to detection or to effects on tumor biology is not known. This study used polygenic models for obesity and breast cancer to deconstruct this question with the objective of determining whether cell autonomous mechanisms contribute to the link between obesity and breast cancer burden. Assessment of the growth rates of 259 chemically induced mammary carcinomas from rats sensitive to dietary induced obesity (DS) and of 143 carcinomas from rats resistant (DR) to dietary induced obesity revealed that tumors in DS rats grew 1.8 times faster than in DR rats. This difference may be attributed to alterations in cell cycle machinery that permit more rapid tumor cell accumulation. DS tumors displayed protein expression patterns consistent with reduced G1/S checkpoint inhibition and a higher threshold of factors required for execution of the apoptotic cell death pathway. These mechanistic insights identify regulatory targets for life style modifications or pharmacological interventions designed to disrupt the linkage between obesity and tumor burden. PMID:27077880

  4. Effects of recombinant epidermal growth factor receptor antisense adenovirus combined with irradiation on breast cancer cells

    International Nuclear Information System (INIS)

    Objective: To investigate the effects of a recombinant antisense adenovirus for epidermal growth factor receptor (EGFR) combined with irradiation on breast cancer cells. Methods: Human EGFR cDNA fragment was subcloned in the opposite orientation to the cytomegaloviral promoter and inserted into a E1/E3-deleted type 5 adenoviral vector to obtain AdE5 construct which expresses EGFR antisense RNA. Combined with γ-ray irradiation, its effects on clonogenicity and cell cycle phase distribution were studied in a human breast cancer line MDA-MB-23. Results: EGFR protein expression was dramatically inhibited in MDA-MB-231 cells after AdE5 infection. The post-irradiation clonogenicity was reduced by AdE5 in a viral and irradiation dose-dependent manner. Further cytometric analysis showed that AdE5 infection at a MOI of 300 pfu/cell induced a cell cycle progression from radio-resistant G0 + G1 phases to radiosensitive G2 + M phases, resulting in a synergistic effect after combination of these two treatments. Conclusions: The transduction of EGFR antisense RNA by adenoviral vector is effective for antisense strategy targeting EGFR, and increases the cell-killing effect of ionizing radiation on breast cancer cells.(authors)

  5. Hispolon inhibits the growth of estrogen receptor positive human breast cancer cells through modulation of estrogen receptor alpha.

    Science.gov (United States)

    Jang, Eun Hyang; Jang, Soon Young; Cho, In-Hye; Hong, Darong; Jung, Bom; Park, Min-Ju; Kim, Jong-Ho

    2015-08-01

    Human estrogen receptor α (ERα) is a nuclear transcription factor that is a major therapeutic target in breast cancer. The transcriptional activity of ERα is regulated by certain estrogen-receptor modulators. Hispolon, isolated from Phellinus linteus, a traditional medicinal mushroom called Sanghwang in Korea, has been used to treat various pathologies, such as inflammation, gastroenteric disorders, lymphatic diseases, and cancers. In this latter context, Hispolon has been reported to exhibit therapeutic efficacy against various cancer cells, including melanoma, leukemia, hepatocarcinoma, bladder cancer, and gastric cancer cells. However, ERα regulation by Hispolon has not been reported. In this study, we investigated the effects of Hispolon on the growth of breast cancer cells. We found that Hispolon decreased expression of ERα at both mRNA and the protein levels in MCF7 and T47D human breast cancer cells. Luciferase reporter assays showed that Hispolon decreased the transcriptional activity of ERα. Hispolon treatment also inhibited expression of the ERα target gene pS2. We propose that Hispolon, an anticancer drug extracted from natural sources, inhibits cell growth through modulation of ERα in estrogen-positive breast cancer cells and is a candidate for use in human breast cancer chemotherapy. PMID:26056942

  6. EZH2 knockdown suppresses the growth and invasion of human inflammatory breast cancer cells

    OpenAIRE

    Mu, Zhaomei; Li, Hua; Fernandez, Sandra V.; Alpaugh, Katherine R; Zhang, Rugang; Cristofanilli, Massimo

    2013-01-01

    Introduction Inflammatory breast cancer (IBC) is the most metastatic variant of breast cancer with the poorest survival in all types of breast cancer patients and presently therapeutic targets for IBC are very limited. Enhancer of zeste homolog 2 (EZH2) is frequently expressed in human IBC and its expression positively correlates with worse clinical outcome. However, the molecular basis for EZH2 promoting IBC has not been explored. Here, we investigated the functional role of EZH2 in IBC cell...

  7. Benzopyrene exposure disrupts DNA methylation and growth dynamics in breast cancer cells

    International Nuclear Information System (INIS)

    Exposures to environmental carcinogens and unhealthy lifestyle choices increase the incidence of breast cancer. One such compound, benzo(a)pyrene (BaP), leads to covalent DNA modifications and the deregulation of gene expression. To date, these mechanisms of BaP-induced carcinogenesis are poorly understood, particularly in the case of breast cancer. We tested the effects of BaP exposure on cellular growth dynamics and DNA methylation in four breast cancer cell lines since disruptions in DNA methylation lead to deregulated gene expression and the loss of genomic integrity. We observed robust time- and concentration-dependent loss of proliferation, S phase and G2M accumulation and apoptosis in p53 positive MCF-7 and T47-D cells. We observed minimal responses in p53 negative HCC-1086 and MDA MB 231 cells. Furthermore, BaP increased p53 levels in both p53 positive cell lines, as well as p21 levels in MCF-7 cells, an effect that was prevented by the p53-specific inhibitor pifithrin-α. No changes in global levels of DNA methylation levels induced by BaP were detected by the methyl acceptor assay (MAA) in any cell line, however, methylation profiling by AIMS (amplification of intermethylated sites) analysis showed dynamic, sequence-specific hypo- and hypermethylation events in all cell lines. We also identified BaP-induced hypomethylation events at a number of genomic repeats. Our data confirm the p53-specific disruption of the cell cycle as well as the disruption of DNA methylation as a consequence of BaP treatment, thus reinforcing the link between environmental exposures, DNA methylation and breast cancer

  8. Proteomic analysis of pathways involved in estrogen-induced growth and apoptosis of breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Zhang-Zhi Hu

    Full Text Available BACKGROUND: Estrogen is a known growth promoter for estrogen receptor (ER-positive breast cancer cells. Paradoxically, in breast cancer cells that have been chronically deprived of estrogen stimulation, re-introduction of the hormone can induce apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: Here, we sought to identify signaling networks that are triggered by estradiol (E2 in isogenic MCF-7 breast cancer cells that undergo apoptosis (MCF-7:5C versus cells that proliferate upon exposure to E2 (MCF-7. The nuclear receptor co-activator AIB1 (Amplified in Breast Cancer-1 is known to be rate-limiting for E2-induced cell survival responses in MCF-7 cells and was found here to also be required for the induction of apoptosis by E2 in the MCF-7:5C cells. Proteins that interact with AIB1 as well as complexes that contain tyrosine phosphorylated proteins were isolated by immunoprecipitation and identified by mass spectrometry (MS at baseline and after a brief exposure to E2 for two hours. Bioinformatic network analyses of the identified protein interactions were then used to analyze E2 signaling pathways that trigger apoptosis versus survival. Comparison of MS data with a computationally-predicted AIB1 interaction network showed that 26 proteins identified in this study are within this network, and are involved in signal transduction, transcription, cell cycle regulation and protein degradation. CONCLUSIONS: G-protein-coupled receptors, PI3 kinase, Wnt and Notch signaling pathways were most strongly associated with E2-induced proliferation or apoptosis and are integrated here into a global AIB1 signaling network that controls qualitatively distinct responses to estrogen.

  9. STAT6 Mediates Interleukin-4 Growth Inhibition in Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Jennifer L. Gooch

    2002-01-01

    Full Text Available In addition to acting as a hematopoietic growth factor, interleukin-4 (IL-4 inhibits growth of some transformed cells in vitro and in vivo. In this study, we show that insulin receptor substrate (IRS-1, IRS-2, and signal transducer and activator of transcription 6 (STAT6 are phosphorylated following IL-4 treatment in MCF-7 breast cancer cells. STAT6 DNA binding is enhanced by IL-4 treatment. STAT6 activation occurs even after IRS-1 depletion, suggesting the two pathways are independent. To examine the role of STAT6 in IL-4-mediated growth inhibition and apoptosis, a fulllength STAT6 cDNA was transfected into MCF-7 cells. Transient overexpression of STAT6 resulted in both cytoplasmic and nuclear expression of the protein, increased DNA binding in response to IL-4, and increased transactivation of an IL-4 responsive promoter. In STAT6-transfected cells, basal proliferation was reduced whereas apoptosis was increased. Finally, stable expression of STAT6 resulted in reduced foci formation compared to vector-transfected cells alone. These results suggest STAT6 is required for IL-4mediated growth inhibition and induction of apoptosis in human breast cancer cells.

  10. Breast cancer tumor growth is efficiently inhibited by dendritic cell transfusion in a murine model

    Directory of Open Access Journals (Sweden)

    Viet Quoc Pham

    2014-03-01

    Full Text Available The ability of dendritic cells to efficiently present tumor-derived antigens when primed with tumor cell lysates makes them attractive as an approach for cancer treatment. This study aimed to evaluate the effects of dendritic cell transfusion dose on breast cancer tumor growth in a murine model. Dendritic cells were produced from allogeneic bone marrow-derived mononuclear cells that were cultured in RPMI 1640 medium supplemented with 20 ng/mL GM-CSF and 20 ng/mL IL-4 for 7 days. These cells were checked for maturation before being primed with a cancer cell-derived antigen. Cancer cell antigens were produced by a rapid freeze-thaw procedure using a 4T1 cell line. Immature dendritic cells were loaded with 4T1 cellderived antigens. Dendritic cells were transfused into mice bearing tumors at three different doses, included 5.104, 105, and 106 cells/mouse with a control consisting of RPMI 1640 media alone. The results showed that dendritic cell therapy inhibited breast cancer tumors in a murine model; however, this effect depended on dendritic cell dose. After 17 days, in the treated groups, tumor size decreased by 43%, 50%, and 87.5% for the doses of 5 and times; 104, 105, and 106 dendritic cells, respectively, while tumor size in the control group decreased by 44%. This result demonstrated that dendritic cell therapy is a promising therapy for breast cancer treatment. [Biomed Res Ther 2014; 1(3.000: 85-92

  11. Targeting the Transforming Growth Factor-β pathway inhibits human basal-like breast cancer metastasis

    Directory of Open Access Journals (Sweden)

    Biswas Swati

    2010-05-01

    Full Text Available Abstract Background Transforming Growth Factor β (TGF-β plays an important role in tumor invasion and metastasis. We set out to investigate the possible clinical utility of TGF-β antagonists in a human metastatic basal-like breast cancer model. We examined the effects of two types of the TGF-β pathway antagonists (1D11, a mouse monoclonal pan-TGF-β neutralizing antibody and LY2109761, a chemical inhibitor of TGF-β type I and II receptor kinases on sublines of basal cell-like MDA-MB-231 human breast carcinoma cells that preferentially metastasize to lungs (4175TR, 4173 or bones (SCP2TR, SCP25TR, 2860TR, 3847TR. Results Both 1D11 and LY2109761 effectively blocked TGF-β-induced phosphorylation of receptor-associated Smads in all MDA-MB-231 subclones in vitro. Moreover, both antagonists inhibited TGF-β stimulated in vitro migration and invasiveness of MDA-MB-231 subclones, indicating that these processes are partly driven by TGF-β. In addition, both antagonists significantly reduced the metastatic burden to either lungs or bones in vivo, seemingly independently of intrinsic differences between the individual tumor cell clones. Besides inhibiting metastasis in a tumor cell autonomous manner, the TGF-β antagonists inhibited angiogenesis associated with lung metastases and osteoclast number and activity associated with lytic bone metastases. In aggregate, these studies support the notion that TGF-β plays an important role in both bone-and lung metastases of basal-like breast cancer, and that inhibiting TGF-β signaling results in a therapeutic effect independently of the tissue-tropism of the metastatic cells. Targeting the TGF-β pathway holds promise as a novel therapeutic approach for metastatic basal-like breast cancer. Conclusions In aggregate, these studies support the notion that TGF-β plays an important role in both bone-and lung metastases of basal-like breast cancer, and that inhibiting TGF-β signaling results in a therapeutic

  12. Imaging male breast cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-11-15

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

  13. Inhibition of Type I Insulin-Like Growth Factor Receptor Signaling Attenuates the Development of Breast Cancer Brain Metastasis

    OpenAIRE

    Saldana, Sandra M.; Lee, Heng-Huan; Lowery, Frank J; Khotskaya, Yekaterina B.; Xia, Weiya; Zhang, Chenyu; Chang, Shih-Shin; Chou, Chao-Kai; Steeg, Patricia S; Yu, Dihua; Hung, Mien-Chie

    2013-01-01

    Brain metastasis is a common cause of mortality in cancer patients, yet potential therapeutic targets remain largely unknown. The type I insulin-like growth factor receptor (IGF-IR) is known to play a role in the progression of breast cancer and is currently being investigated in the clinical setting for various types of cancer. The present study demonstrates that IGF-IR is constitutively autophosphorylated in brain-seeking breast cancer sublines. Knockdown of IGF-IR results in a decrease of ...

  14. Natural product ginsenoside 25-OCH3-PPD inhibits breast cancer growth and metastasis through down-regulating MDM2.

    Directory of Open Access Journals (Sweden)

    Wei Wang

    Full Text Available Although ginseng and related herbs have a long history of utility for various health benefits, their application in cancer therapy and underlying mechanisms of action are not fully understood. Our recent work has shown that 20(S-25-methoxyl-dammarane-3β, 12β, 20-triol (25-OCH(3-PPD, a newly identified ginsenoside from Panax notoginseng, exerts activities against a variety of cancer cells in vitro and in vivo. This study was designed to investigate its anti-breast cancer activity and the underlying mechanisms of action. We observed that 25-OCH(3-PPD decreased the survival of breast cancer cells by induction of apoptosis and G1 phase arrest and inhibited the growth of breast cancer xenografts in vivo. We further demonstrated that, in a dose- and time-dependent manner, 25-OCH(3-PPD inhibited MDM2 expression at both transcriptional and post-translational levels in human breast cancer cells with various p53 statuses (wild type and mutant. Moreover, 25-OCH(3-PPD inhibited in vitro cell migration, reduced the expression of epithelial-to-mesenchymal transition (EMT markers, and prevented in vivo metastasis of breast cancer. In summary, 25-OCH(3-PPD is a potential therapeutic and anti-metastatic agent for human breast cancer through down-regulating MDM2. Further preclinical and clinical development of this agent is warranted.

  15. Association Between Vascular Endothelial Growth Factor Gene Polymorphisms with Breast Cancer Risk in an Iranian Population

    OpenAIRE

    Rezaei, Maryam; Hashemi, Mohammad; Sanaei, Sara; Mashhadi, Mohammad Ali; Taheri, Mohsen

    2016-01-01

    Breast cancer (BC) is one of the most causes of death in women worldwide. It affects Iranian female population approximately a decade earlier than those in other parts of the world. Previous studies have shown that vascular endothelial growth factor (VEGF) gene variants were associated with BC risk. The current study aimed to evaluate the impact of VEGF rs3025039 (+936C>T), rs2010963 (+405C>G), rs833061 (-460T>C), rs699947 (-2578C>A), and rs35569394 (18-bp I/D) polymorphisms on BC risk in an ...

  16. Withaferin A inhibits in vivo growth of breast cancer cells accelerated by Notch2 knockdown.

    Science.gov (United States)

    Kim, Su-Hyeong; Hahm, Eun-Ryeong; Arlotti, Julie A; Samanta, Suman K; Moura, Michelle B; Thorne, Stephen H; Shuai, Yongli; Anderson, Carolyn J; White, Alexander G; Lokshin, Anna; Lee, Joomin; Singh, Shivendra V

    2016-05-01

    The present study offers novel insights into the molecular circuitry of accelerated in vivo tumor growth by Notch2 knockdown in triple-negative breast cancer (TNBC) cells. Therapeutic vulnerability of Notch2-altered growth to a small molecule (withaferin A, WA) is also demonstrated. MDA-MB-231 and SUM159 cells were used for the xenograft studies. A variety of technologies were deployed to elucidate the mechanisms underlying tumor growth augmentation by Notch2 knockdown and its reversal by WA, including Fluorescence Molecular Tomography for measurement of tumor angiogenesis in live mice, Seahorse Flux analyzer for ex vivo measurement of tumor metabolism, proteomics, and Luminex-based cytokine profiling. Stable knockdown of Notch2 resulted in accelerated in vivo tumor growth in both cells reflected by tumor volume and/or latency. For example, the wet tumor weight from mice bearing Notch2 knockdown MDA-MB-231 cells was about 7.1-fold higher compared with control (P medicinal plant. Molecular underpinnings for tumor growth intensification by Notch2 knockdown included compensatory increase in Notch1 activation, increased cellular proliferation and/or angiogenesis, and increased plasma or tumor levels of growth stimulatory cytokines. WA administration reversed many of these effects providing explanation for its remarkable anti-cancer efficacy. Notch2 functions as a tumor growth suppressor in TNBC and WA offers a novel therapeutic strategy for restoring this function. PMID:27097807

  17. Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells.

    Science.gov (United States)

    Zakikhani, Mahvash; Dowling, Ryan; Fantus, I George; Sonenberg, Nahum; Pollak, Michael

    2006-11-01

    Recent population studies provide clues that the use of metformin may be associated with reduced incidence and improved prognosis of certain cancers. This drug is widely used in the treatment of type 2 diabetes, where it is often referred to as an "insulin sensitizer" because it not only lowers blood glucose but also reduces the hyperinsulinemia associated with insulin resistance. As insulin and insulin-like growth factors stimulate proliferation of many normal and transformed cell types, agents that facilitate signaling through these receptors would be expected to enhance proliferation. We show here that metformin acts as a growth inhibitor rather than an insulin sensitizer for epithelial cells. Breast cancer cells can be protected against metformin-induced growth inhibition by small interfering RNA against AMP kinase. This shows that AMP kinase pathway activation by metformin, recently shown to be necessary for metformin inhibition of gluconeogenesis in hepatocytes, is also involved in metformin-induced growth inhibition of epithelial cells. The growth inhibition was associated with decreased mammalian target of rapamycin and S6 kinase activation and a general decrease in mRNA translation. These results provide evidence for a mechanism that may contribute to the antineoplastic effects of metformin suggested by recent population studies and justify further work to explore potential roles for activators of AMP kinase in cancer prevention and treatment. PMID:17062558

  18. Sunitinib significantly suppresses the proliferation, migration, apoptosis resistance, tumor angiogenesis and growth of triple-negative breast cancers but increases breast cancer stem cells.

    Science.gov (United States)

    Chinchar, Edmund; Makey, Kristina L; Gibson, John; Chen, Fang; Cole, Shelby A; Megason, Gail C; Vijayakumar, Srinivassan; Miele, Lucio; Gu, Jian-Wei

    2014-01-01

    The majority of triple-negative breast cancers (TNBCs) are basal-like breast cancers. However there is no reported study on anti-tumor effects of sunitinib in xenografts of basal-like TNBC (MDA-MB-468) cells. In the present study, MDA-MB-231, MDA-MB-468, MCF-7 cells were cultured using RPMI 1640 media with 10% FBS. Vascular endothelia growth factor (VEGF) protein levels were detected using ELISA (R & D Systams). MDA-MB-468 cells were exposed to sunitinib for 18 hours for measuring proliferation (3H-thymidine incorporation), migration (BD Invasion Chamber), and apoptosis (ApopTag and ApoScreen Anuexin V Kit). The effect of sunitinib on Notch-1 expression was determined by Western blot in cultured MDA-MB-468 cells. 10(6) MDA-MB-468 cells were inoculated into the left fourth mammary gland fat pad in athymic nude-foxn1 mice. When the tumor volume reached 100 mm(3), sunitinib was given by gavage at 80 mg/kg/2 days for 4 weeks. Tumor angiogenesis was determined by CD31 immunohistochemistry. Breast cancer stem cells (CSCs) isolated from the tumors were determined by flow cytometry analysis using CD44(+)/CD24(-) or low. ELISA indicated that VEGF was much more highly expressed in MDA-MB-468 cells than MDA-MB-231 and MCF-7 cells. Sunitinib significantly inhibited the proliferation, invasion, and apoptosis resistance in cultured basal like breast cancer cells. Sunitinib significantly increased the expression of Notch-1 protein in cultured MDA-MB-468 or MDA-MB-231 cells. The xenograft models showed that oral sunitinib significantly reduced the tumor volume of TNBCs in association with the inhibition of tumor angiogeneisis, but increased breast CSCs. These findings support the hypothesis that the possibility should be considered of sunitinib increasing breast CSCs though it inhibits TNBC tumor angiogenesis and growth/progression, and that effects of sunitinib on Notch expression and hypoxia may increase breast cancer stem cells. This work provides the groundwork for an

  19. Vernonia amygdalina—Induced Growth Arrest and Apoptosis of Breast Cancer (MCF-7) Cells

    OpenAIRE

    Yedjou, Clement G.; Izevbigie, Ernest B.; Tchounwou, Paul B.

    2013-01-01

    Breast cancer is the second leading cause of cancer-related deaths of women in the United States. Fortunately, the mortality rate from breast cancer has decreased in recent years due to an increased emphasis on early detection and more effective treatments. Although great advancements have been made in the treatment and control of cancer progression, significant deficiencies and room for improvement remain. The central objective of this research was to further determine the in vitro mechanism...

  20. The effects of radiotherapy on the hormone receptor concentration and tumor growth in xenotransplanted human breast cancer

    International Nuclear Information System (INIS)

    The influence of radiotherapy on tumor growth and hormone receptor concentration (estrogen-, progesteronreceptor) in xenotransplanted human breast cancer is observed. Tumor growth significantly is delayed under therapy during the first 35 days after radiation. Renewed growth follows after that time. After the first days of treatment the ER and PR concentration decreases considerably and finally reaches 40% respectively 30% of the pretreatment level for a period of approximately 35 days after the end of radiotherapy. In general radiation therapy seems to affect the PR stronger than the ER. After this period ER and PR levels increase again with the regrowing tumor. The results point out that radiotherapy reduces the concentration of ER and PR in human breast cancer. Therefore the assay of steroid receptors in human breast cancer after radiation therapy is useful in predicting hormone dependency and prognosis only when receptor concentrations are positive. (orig.)

  1. Aurora kinase B is important for antiestrogen resistant cell growth and a potential biomarker for tamoxifen resistant breast cancer

    DEFF Research Database (Denmark)

    Larsen, Sarah L; Yde, Christina W; Laenkholm, Anne-Vibeke;

    2015-01-01

    endocrine resistance, immunohistochemistry was performed on archival primary tumor tissue from breast cancer patients who have received adjuvant endocrine treatment with tamoxifen. RESULTS: The selective Aurora kinase B inhibitor barasertib was identified to preferentially inhibit growth of fulvestrant...... and PARP cleavage in the fulvestrant resistant cells. Barasertib also exerted preferential growth inhibition of tamoxifen resistant T47D cell lines. Finally, high percentage of Aurora kinase B positive tumor cells was significantly associated with reduced disease-free and overall survival in 261 ER......-positive breast cancer patients, who have received tamoxifen as first-line adjuvant endocrine treatment. CONCLUSIONS: Our results indicate that Aurora kinase B is a driving factor for growth of antiestrogen resistant T47D breast cancer cell lines, and a biomarker for reduced benefit of tamoxifen treatment. Thus...

  2. Dopamine receptor antagonist thioridazine inhibits tumor growth in a murine breast cancer model.

    Science.gov (United States)

    Yin, Tao; He, Sisi; Shen, Guobo; Ye, Tinghong; Guo, Fuchun; Wang, Yongsheng

    2015-09-01

    Neuropsychological factors have been shown to influence tumor progression and therapeutic response. The present study investigated the effect of the dopamine receptor antagonist thioridazine on murine breast cancer. The anti‑tumor efficacy of thioridazine was assessed using a murine breast cancer model. Cell apoptosis and proliferation were analyzed in vitro using flow cytometry (FCM) and the MTT assay, respectively. Western blot analysis was performed to assess Akt, phosphorylated (p)‑Akt, signal transducer and activator of transcription (STAT) 3, p‑STAT3 and p‑p65 in tumor cells following treatment with thioridazine. The Ki67 index and the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)‑positive apoptotic cells were assessed in the tumor sections. Thioridazine was found to reduce tumor growth, inhibit tumor cell proliferation and induce apoptosis in a dose‑ and time‑dependent manner in vitro. Thioridazine was also found to markedly inhibit tumor proliferation and induce tumor cell apoptosis in vivo as shown by the lower Ki67 index and increase in TUNEL‑positive cells. In addition, thioridazine was observed to inhibit the activation of the canonical nuclear factor κ‑light‑chain‑enhancer of activated B cells pathway and exert anti‑tumor effects by remodeling the tumor stroma, as well as inhibit angiogenesis in the tumor microenvironment. In conclusion, thioridazine was found to significantly inhibit breast tumor growth and the potential for thioridazine to be used in cancer therapy may be re‑evaluated and investigated in clinical settings. PMID:26095429

  3. ING1 and 5-Azacytidine Act Synergistically to Block Breast Cancer Cell Growth

    Science.gov (United States)

    Thakur, Satbir; Feng, Xiaolan; Qiao Shi, Zhong; Ganapathy, Amudha; Kumar Mishra, Manoj; Atadja, Peter; Morris, Don; Riabowol, Karl

    2012-01-01

    Background Inhibitor of Growth (ING) proteins are epigenetic “readers” that recognize trimethylated lysine 4 of histone H3 (H3K4Me3) and target histone acetyl transferase (HAT) and histone deacetylase (HDAC) complexes to chromatin. Methods and Principal Findings Here we asked whether dysregulating two epigenetic pathways with chemical inhibitors showed synergistic effects on breast cancer cell line killing. We also tested whether ING1 could synergize better with chemotherapeutics that target the same epigenetic mechanism such as the HDAC inhibitor LBH589 (Panobinostat) or a different epigenetic mechanism such as 5-azacytidine (5azaC), which inhibits DNA methyl transferases. Simultaneous treatment of breast cancer cell lines with LBH589 and 5azaC did not show significant synergy in killing cells. However, combination treatment of ING1 with either LBH589 or 5azaC did show synergy. The combination of ING1b with 5azaC, which targets two distinct epigenetic mechanisms, was more effective at lower doses and enhanced apoptosis as determined by Annexin V staining and cleavage of caspase 3 and poly-ADP-ribose polymerase (PARP). ING1b plus 5azaC also acted synergistically to increase γH2AX staining indicating significant levels of DNA damage were induced. Adenoviral delivery of ING1b with 5azaC also inhibited cancer cell growth in a murine xenograft model and led to tumor regression when viral concentration was optimized in vivo. Conclusions These data show that targeting distinct epigenetic pathways can be more effective in blocking cancer cell line growth than targeting the same pathway with multiple agents, and that using viral delivery of epigenetic regulators can be more effective in synergizing with a chemical agent than using two chemotherapeutic agents. This study also indicates that the ING1 epigenetic regulator may have additional activities in the cell when expressed at high levels. PMID:22916295

  4. ING1 and 5-azacytidine act synergistically to block breast cancer cell growth.

    Directory of Open Access Journals (Sweden)

    Satbir Thakur

    Full Text Available BACKGROUND: Inhibitor of Growth (ING proteins are epigenetic "readers" that recognize trimethylated lysine 4 of histone H3 (H3K4Me3 and target histone acetyl transferase (HAT and histone deacetylase (HDAC complexes to chromatin. METHODS AND PRINCIPAL FINDINGS: Here we asked whether dysregulating two epigenetic pathways with chemical inhibitors showed synergistic effects on breast cancer cell line killing. We also tested whether ING1 could synergize better with chemotherapeutics that target the same epigenetic mechanism such as the HDAC inhibitor LBH589 (Panobinostat or a different epigenetic mechanism such as 5-azacytidine (5azaC, which inhibits DNA methyl transferases. Simultaneous treatment of breast cancer cell lines with LBH589 and 5azaC did not show significant synergy in killing cells. However, combination treatment of ING1 with either LBH589 or 5azaC did show synergy. The combination of ING1b with 5azaC, which targets two distinct epigenetic mechanisms, was more effective at lower doses and enhanced apoptosis as determined by Annexin V staining and cleavage of caspase 3 and poly-ADP-ribose polymerase (PARP. ING1b plus 5azaC also acted synergistically to increase γH2AX staining indicating significant levels of DNA damage were induced. Adenoviral delivery of ING1b with 5azaC also inhibited cancer cell growth in a murine xenograft model and led to tumor regression when viral concentration was optimized in vivo. CONCLUSIONS: These data show that targeting distinct epigenetic pathways can be more effective in blocking cancer cell line growth than targeting the same pathway with multiple agents, and that using viral delivery of epigenetic regulators can be more effective in synergizing with a chemical agent than using two chemotherapeutic agents. This study also indicates that the ING1 epigenetic regulator may have additional activities in the cell when expressed at high levels.

  5. The chalcone butein from Rhus verniciflua Stokes inhibits clonogenic growth of human breast cancer cells co-cultured with fibroblasts

    Directory of Open Access Journals (Sweden)

    Tan Jenny

    2005-03-01

    Full Text Available Abstract Background Butein (3,4,2',4'-tetrahydroxychalone, a plant polyphenol, is a major biologically active component of the stems of Rhus verniciflua Stokes. It has long been used as a food additive in Korea and as an herbal medicine throughout Asia. Recently, butein has been shown to suppress the functions of fibroblasts. Because fibroblasts are believed to play an important role in promoting the growth of breast cancer cells, we investigated the ability of butein to inhibit the clonogenic growth of small numbers of breast cancer cells co-cultured with fibroblasts in vitro. Methods We first measured the clonogenic growth of small numbers of the UACC-812 human breast cancer cell line co-cultured on monolayers of serum-activated, human fibroblasts in the presence of butein (2 μg/mL or various other modulators of fibroblast function (troglitazone-1 μg/mL; GW9662-1 μM; meloxican-1 μM; and 3,4 dehydroproline-10 μg/mL. In a subsequent experiment, we measured the dose-response effect on the clonogenic growth of UACC-812 breast cancer cells by pre-incubating the fibroblasts with varying concentrations of butein (10 μg/ml-1.25 μg/mL. Finally, we measured the clonogenic growth of primary breast cancer cells obtained from 5 clinical specimens with normal fibroblasts and with fibroblasts that had been pre-treated with a fixed dose of butein (2.5 μg/mL. Results Of the five modulators of fibroblast function that we tested, butein was by far the most potent inhibitor of clonogenic growth of UACC-812 breast cancer cells co-cultured with fibroblasts. Pre-treatment of fibroblasts with concentrations of butein as low as 2.5 μg/mL nearly abolished subsequent clonogenic growth of UACC-812 breast cancer cells co-cultured with the fibroblasts. A similar dose of butein had no effect on the clonogenic growth of breast cancer cells cultured in the absence of fibroblasts. Significantly, clonogenic growth of the primary breast cancer cells was also

  6. Pttg1 Promotes Growth of Breast Cancer through P27 Nuclear Exclusion

    Directory of Open Access Journals (Sweden)

    Yishan Xiea

    2016-01-01

    Full Text Available Background/Aims: A role of Pituitary Tumor Transforming Gene 1 (Pttg1 in the carcinogenesis has been shown in some cancers, but not in BC (BC. Methods: We compared the levels of Pttg1 in the resected BC tissue with the adjacent normal breast tissue from the same patient. We modified Pttg1 levels in a BC cell line, MCF7, by either a Pttg1 transgene, or a Pttg1 shRNA. The cell growth was measured in an MTT assay. The cell apoptosis was measured by apoptosis assay. The nuclear protein of cell-cycle-related genes was examined in Pttg1-modifed BC cells. Co-immunoprecipitation was performed to examine the association of Pttg1 and p27. Results: We detected significantly higher levels of Pttg1 in the resected BC tissue, compared to the adjacent normal breast tissue from the same patient. Overexpression or depletion of Pttg1 in MCF7 significantly increased or inhibited cell growth, respectively. Changes in Pttg1 levels, however, did not alter cell apoptosis, suggesting that Pttg1 increases cell growth through augmented cell proliferation, rather than decreased cell apoptosis. Among all examined cell-cycle-related proteins in Pttg1-modifed BC cells, only nuclear p27 levels were significantly affected. Further, co-immunoprecipitation showed that Pttg1 directly associated with p27. Conclusion: Pttg1 may increase BC cell growth through nuclear exclusion of p27, which highlights a novel molecular regulatory machinery in tumorigenesis of BC.

  7. Phenotype-dependent effects of EpCAM expression on growth and invasion of human breast cancer cell lines

    International Nuclear Information System (INIS)

    The epithelial cell adhesion molecule (EpCAM) has been shown to be overexpressed in breast cancer and stem cells and has emerged as an attractive target for immunotherapy of breast cancer patients. This study analyzes the effects of EpCAM on breast cancer cell lines with epithelial or mesenchymal phenotype. For this purpose, shRNA-mediated knockdown of EpCAM gene expression was performed in EpCAMhigh breast cancer cell lines with epithelial phenotype (MCF-7, T47D and SkBR3). Moreover, EpCAMlow breast carcinoma cell lines with mesenchymal phenotype (MDA-MB-231, Hs578t) and inducible overexpression of EpCAM were used to study effects on proliferation, migration and in vivo growth. In comparison to non-specific silencing controls (n/s-crtl) knockdown of EpCAM (E#2) in EpCAMhigh cell lines resulted in reduced cell proliferation under serum-reduced culture conditions. Moreover, DNA synthesis under 3D culture conditions in collagen was significantly reduced. Xenografts of MCF-7 and T47D cells with knockdown of EpCAM formed smaller tumors that were less invasive. EpCAMlow cell lines with tetracycline-inducible overexpression of EpCAM showed no increased cell proliferation or migration under serum-reduced growth conditions. MDA-MB-231 xenografts with EpCAM overexpression showed reduced invasion into host tissue and more infiltrates of chicken granulocytes. The role of EpCAM in breast cancer strongly depends on the epithelial or mesenchymal phenotype of tumor cells. Cancer cells with epithelial phenotype need EpCAM as a growth- and invasion-promoting factor, whereas tumor cells with a mesenchymal phenotype are independent of EpCAM in invasion processes and tumor progression. These findings might have clinical implications for EpCAM-based targeting strategies in patients with invasive breast cancer

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

    OpenAIRE

    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 ce...

  9. Dissecting the Role of Curcumin in Tumour Growth and Angiogenesis in Mouse Model of Human Breast Cancer

    Directory of Open Access Journals (Sweden)

    Sabrina Bimonte

    2015-01-01

    Full Text Available Breast cancer is considered the most common cancer for women worldwide and it is now the second leading cause of cancer-related deaths among females in the world. Since breast cancer is highly resistant to chemotherapy, alternative anticancer strategies have been developed. In particular, many studies have demonstrated that curcumin, a derivative of turmeric, can be used as natural agent in treatment of some types of cancer by playing antiproliferative and antioxidant effects. In our study, we assessed the antitumor activities of curcumin in ER-negative human breast cancer cell line resistant to chemotherapy, MDA.MB231 by in vitro and in vivo experiments. In vitro data allowed us to demonstrate that curcumin played a role in regulation of proliferation and apoptosis in MDA.MB231 cells. In vivo, by generation of mouse model of breast cancer, we showed that treatment of curcumin inhibited tumor growth and angiogenesis. Specifically, we showed that curcumin is able to deregulate the expression of cyclin D1, PECAM-1, and p65, which are regulated by NF-κB. Our data demonstrated that curcumin could be used as an adjuvant agent to chemotherapy in treatment of triple negative breast cancer.

  10. PH motifs in PAR1&2 endow breast cancer growth.

    Science.gov (United States)

    Kancharla, A; Maoz, M; Jaber, M; Agranovich, D; Peretz, T; Grisaru-Granovsky, S; Uziely, B; Bar-Shavit, R

    2015-01-01

    Although emerging roles of protease-activated receptor1&2 (PAR1&2) in cancer are recognized, their underlying signalling events are poorly understood. Here we show signal-binding motifs in PAR1&2 that are critical for breast cancer growth. This occurs via the association of the pleckstrin homology (PH) domain with Akt/PKB as a key signalling event of PARs. Other PH-domain signal-proteins such as Etk/Bmx and Vav3 also associate with PAR1 and PAR2 through their PH domains. PAR1 and PAR2 bind with priority to Etk/Bmx. A point mutation in PAR2, H349A, but not in R352A, abrogates PH-protein association and is sufficient to markedly reduce PAR2-instigated breast tumour growth in vivo and placental extravillous trophoblast (EVT) invasion in vitro. Similarly, the PAR1 mutant hPar1-7A, which is unable to bind the PH domain, reduces mammary tumours and EVT invasion, endowing these motifs with physiological significance and underscoring the importance of these previously unknown PAR1 and PAR2 PH-domain-binding motifs in both pathological and physiological invasion processes. PMID:26600192

  11. Relationships between explanatory style, posttraumatic growth and posttraumatic stress disorder symptoms among Chinese breast cancer patients.

    Science.gov (United States)

    Ho, Samuel M Y; Chan, Michelle W Y; Yau, T K; Yeung, Rebecca M W

    2011-03-01

    Many existing models posit that cognitive processing style is an important factor affecting self-perceived positive changes. In this study, the effects of explanatory style (the manner in which people cognitively process and explain why they experience good and bad events) on both posttraumatic growth (PTG) and posttraumatic stress disorder (PTSD) symptoms were examined among 90 Chinese women with breast cancer. It was found that explanatory style for good events, but not for bad events, was significantly associated with self-reported PTG. Women who attributed the causes of positive events to internal, global and stable factors tended to report more posttraumatic growth. In contrast, explanatory style for bad events, as opposed to good events, was significantly and positively correlated with PTSD symptoms. Among the three dimensions of explanatory style (internal, stable and global), the tendency to globalise the causes of good and bad events were the most important predictors of self-reported PTG and PTSD symptoms, respectively. While enhancing an optimistic explanatory style for bad events might reduce posttraumatic stress symptoms, cultivating an optimistic explanatory style for good events is likely to increase self-perceived positive changes after breast cancer diagnosis and treatment. PMID:20204977

  12. Decreased autocrine EGFR signaling in metastatic breast cancer cells inhibits tumor growth in bone and mammary fat pad.

    Science.gov (United States)

    Nickerson, Nicole K; Mohammad, Khalid S; Gilmore, Jennifer L; Crismore, Erin; Bruzzaniti, Angela; Guise, Theresa A; Foley, John

    2012-01-01

    Breast cancer metastasis to bone triggers a vicious cycle of tumor growth linked to osteolysis. Breast cancer cells and osteoblasts express the epidermal growth factor receptor (EGFR) and produce ErbB family ligands, suggesting participation of these growth factors in autocrine and paracrine signaling within the bone microenvironment. EGFR ligand expression was profiled in the bone metastatic MDA-MB-231 cells (MDA-231), and agonist-induced signaling was examined in both breast cancer and osteoblast-like cells. Both paracrine and autocrine EGFR signaling were inhibited with a neutralizing amphiregulin antibody, PAR34, whereas shRNA to the EGFR was used to specifically block autocrine signaling in MDA-231 cells. The impact of these was evaluated with proliferation, migration and gene expression assays. Breast cancer metastasis to bone was modeled in female athymic nude mice with intratibial inoculation of MDA-231 cells, and cancer cell-bone marrow co-cultures. EGFR knockdown, but not PAR34 treatment, decreased osteoclasts formed in vitro (p<0.01), reduced osteolytic lesion tumor volume (p<0.01), increased survivorship in vivo (p<0.001), and resulted in decreased MDA-231 growth in the fat pad (p<0.01). Fat pad shEGFR-MDA-231 tumors produced in nude mice had increased necrotic areas and decreased CD31-positive vasculature. shEGFR-MDA-231 cells also produced decreased levels of the proangiogenic molecules macrophage colony stimulating factor-1 (MCSF-1) and matrix metalloproteinase 9 (MMP9), both of which were decreased by EGFR inhibitors in a panel of EGFR-positive breast cancer cells. Thus, inhibiting autocrine EGFR signaling in breast cancer cells may provide a means for reducing paracrine factor production that facilitates microenvironment support in the bone and mammary gland. PMID:22276166

  13. Decreased autocrine EGFR signaling in metastatic breast cancer cells inhibits tumor growth in bone and mammary fat pad.

    Directory of Open Access Journals (Sweden)

    Nicole K Nickerson

    Full Text Available Breast cancer metastasis to bone triggers a vicious cycle of tumor growth linked to osteolysis. Breast cancer cells and osteoblasts express the epidermal growth factor receptor (EGFR and produce ErbB family ligands, suggesting participation of these growth factors in autocrine and paracrine signaling within the bone microenvironment. EGFR ligand expression was profiled in the bone metastatic MDA-MB-231 cells (MDA-231, and agonist-induced signaling was examined in both breast cancer and osteoblast-like cells. Both paracrine and autocrine EGFR signaling were inhibited with a neutralizing amphiregulin antibody, PAR34, whereas shRNA to the EGFR was used to specifically block autocrine signaling in MDA-231 cells. The impact of these was evaluated with proliferation, migration and gene expression assays. Breast cancer metastasis to bone was modeled in female athymic nude mice with intratibial inoculation of MDA-231 cells, and cancer cell-bone marrow co-cultures. EGFR knockdown, but not PAR34 treatment, decreased osteoclasts formed in vitro (p<0.01, reduced osteolytic lesion tumor volume (p<0.01, increased survivorship in vivo (p<0.001, and resulted in decreased MDA-231 growth in the fat pad (p<0.01. Fat pad shEGFR-MDA-231 tumors produced in nude mice had increased necrotic areas and decreased CD31-positive vasculature. shEGFR-MDA-231 cells also produced decreased levels of the proangiogenic molecules macrophage colony stimulating factor-1 (MCSF-1 and matrix metalloproteinase 9 (MMP9, both of which were decreased by EGFR inhibitors in a panel of EGFR-positive breast cancer cells. Thus, inhibiting autocrine EGFR signaling in breast cancer cells may provide a means for reducing paracrine factor production that facilitates microenvironment support in the bone and mammary gland.

  14. Silibinin inhibits accumulation of myeloid-derived suppressor cells and tumor growth of murine breast cancer

    International Nuclear Information System (INIS)

    Myeloid-derived suppressor cells (MDSC)s increase in blood and accumulate in the tumor microenvironment of tumor-bearing animals, contributing to immune suppression in cancer. Silibinin, a natural flavonoid from the seeds of milk thistle, has been developed as an anti-inflammatory agent and supportive care agent to reduce the toxicity of cancer chemotherapy. The goals of this study were to evaluate the effect of silibinin on MDSCs in tumor-bearing mice and antitumor activity of silibinin in a mouse model of breast cancer. 4T1 luciferase-transfected mammary carcinoma cells were injected into in the mammary fat pad female BALB/c mice, and female CB17-Prkdc Scid/J mice. Silibinin treatment started on day 4 or day 14 after tumor inoculation continued every other day. Tumor growth was monitored by bioluminescent imaging (BLI) measuring total photon flux. Flow cytometry measured total leukocytes, CD11b+ Gr-1+ MDSC, and T cells in the blood and tumors of tumor-bearing mice. The effects of silibinin on 4T1 cell viability in vitro were measured by BLI. Treatment with silibinin increased overall survival in mice harboring tumors derived from the 4T1-luciferase breast cancer cell line, and reduced tumor volumes and numbers of CD11b+Gr-1+ MDSCs in the blood and tumor, and increased the content of T cells in the tumor microenvironment. Silibinin failed to inhibit tumor growth in immunocompromised severe combined immunodeficiency mice, supporting the hypothesis that anticancer effect of silibinin is immune-mediated. The antitumor activity of silibinin requires an intact host immune system and is associated with decreased accumulation of blood and tumor-associated MDSCs

  15. Synthetic matrix metalloproteinase inhibitors inhibit growth of established breast cancer osteolytic lesions and prolong survival in mice

    DEFF Research Database (Denmark)

    Winding, Bent; NicAmhlaoibh, Róisín; Misander, Henriette;

    2002-01-01

    PURPOSE: Breast cancer frequently leads to incurable bone metastasis. Essential requirements for the development of bone metastasis are cell-cell and cell-matrix interactions, release of bioactive growth factors and cytokines, and removal of large amounts of bone matrix. Matrix metalloproteinases...... (MMPs) play an important role in all of these processes, but the possibility of using synthetic MMP inhibitors to decrease bone metastasis has received little attention. EXPERIMENTAL DESIGN: In the present study, we tested two general MMP inhibitors, BB-94 and GM6001, in a mouse model of breast cancer......-induced bone metastasis. RESULTS: In a simulation of intervention therapy, mice were inoculated with breast cancer cells, and at the time of diagnosis of osteolytic lesions, the mice were treated for 10 or 15 consecutive days with BB-94 or GM6001, respectively. Both inhibitors reduced the growth of osteolytic...

  16. Estrogen-mediated mechanisms to control the growth and apoptosis of breast cancer cells: a translational research success story.

    Science.gov (United States)

    McDaniel, Russell E; Maximov, Philipp Y; Jordan, V Craig

    2013-01-01

    The treatment and prevention of solid tumors have proved to be a major challenge for medical science. The paradigms for success in the treatment of childhood leukemia, Hodgkin's disease, Burkett's lymphoma, and testicular carcinoma with cytotoxic chemotherapy did not translate to success in solid tumors--the majority of cancers that kill. In contrast, significant success has accrued for patients with breast cancer with antihormone treatments (tamoxifen or aromatase inhibitors) that are proved to enhance survivorship, and remarkably, there are now two approved prevention strategies using either tamoxifen or raloxifene. This was considered impossible 40 years ago. We describe the major clinical advances with nonsteroidal antiestrogens that evolved into selective estrogen receptor modulators (SERMs) which successfully exploited the ER target selectively inside a woman's body. The standard paradigm that estrogen stimulates breast cancer growth has been successfully exploited for over 4 decades with therapeutic strategies that block (tamoxifen, raloxifene) or reduce (aromatase inhibitors) circulating estrogens in patients to stop breast tumor growth. But this did not explain why high-dose estrogen treatment that was the standard of care to treat postmenopausal breast cancer for 3 decades before tamoxifen caused tumor regression. This paradox was resolved with the discovery that breast cancer resistance to long-term estrogen deprivation causes tumor regression with physiologic estrogen through apoptosis. The new biology of estrogen action has been utilized to explain the findings in the Women's Health Initiative that conjugated equine estrogen alone given to postmenopausal women, average age 68, will produce a reduction of breast cancer incidence and mortality compared to no treatment. Estrogen is killing nascent breast cancer cells in the ducts of healthy postmenopausal women. The modulation of the ER using multifunctional medicines called SERMs has provided not only

  17. Breast cancer staging

    Science.gov (United States)

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

  18. Types of Breast Cancers

    Science.gov (United States)

    ... about this condition, see Inflammatory Breast Cancer . Paget disease of the nipple This type of breast cancer ... carcinoma (this is a type of metaplastic carcinoma) Medullary carcinoma Mucinous (or colloid) carcinoma Papillary carcinoma Tubular ...

  19. Tumor-targeting Salmonella typhimurium A1-R arrests growth of breast-cancer brain metastasis

    OpenAIRE

    Zhang, Yong; Miwa, Shinji; Zhang, Nan; Hoffman, Robert M.; Zhao, Ming

    2014-01-01

    Brain metastasis is a morbid, treatment-resistant, end-stage frequent occurrence in breast cancer patients. The aim of this study was to evaluate the efficacy of tumor-targeting Salmonella typhimurium A1-R on breast cancer brain metastases. High brain-metastatic variants of murine 4T1 breast cancer cells expressing red fluorescent protein (RFP) were injected orthotopically in the mammary fat pad in non-transgenic nude mice or in the left ventricle of non-transgenic nude mice and transgenic nu...

  20. Phellinus linteus extract induces autophagy and synergizes with 5-fluorouracil to inhibit breast cancer cell growth.

    Science.gov (United States)

    Lee, Wen-Ying; Hsu, Keng-Fu; Chiang, Tai-An; Chen, Chee-Jen

    2015-01-01

    Phellinus linteus (PL) is a medicinal mushroom due to its several biological properties, including anticancer activity. However, the mechanisms of its anticancer effect remain to be elucidated. We evaluated the inhibitory effects of the ethanolic extract from the PL combined with 5-FU on MDA-MB-231 breast cancer cell line and to determine the mechanism of cell death. Individually, PL extract and 5-FU significantly inhibited the proliferation of MDA-MB-231 cells in a dose-dependent manner. PL extract (30 mg/mL) in combination with 5-FU (10 μg/mL) synergistically inhibited MDA-MB-231 cells by 1.8-fold. PL did not induce apoptosis, as demonstrated by the DNA fragmentation assay, the sub-G1 population, and staining with annexin V-FITC and propidium iodide. The exposure of MDA-MB-231 cells to PL extracts resulted in several confirmed characteristics of autophagy, including the appearance of autophagic vacuoles revealed by monodansylcadaverine staining, the formation of acidic vesicular organelles, autophagosome membrane association of microtubule-associated protein light chain 3 (LC3) characterized by cleavage of LC3 and its punctuate redistribution, and ultrastructural observation of autophagic vacuoles by transmission electron microscopy. We concluded that PL extracts synergized with low doses of 5-FU to inhibit triple-negative breast cancer cell growth and demonstrated that PL extract can induce autophagy-related cell death. PMID:25622112

  1. Insulin like growth factor 2 regulation of aryl hydrocarbon receptor in MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Tomblin, Justin K.; Salisbury, Travis B., E-mail: salisburyt@marshall.edu

    2014-01-17

    Highlights: •IGF-2 stimulates concurrent increases in AHR and CCND1 expression. •IGF-2 promotes the binding of AHR to the endogenous cyclin D1 promoter. •AHR knockdown inhibits IGF-2 stimulated increases in CCND1 mRNA and protein. •AHR knockdown inhibits IGF-2 stimulated increases in MCF-7 proliferation. -- Abstract: Insulin like growth factor (IGF)-1 and IGF-2 stimulate normal growth, development and breast cancer cell proliferation. Cyclin D1 (CCND1) promotes cell cycle by inhibiting retinoblastoma protein (RB1). The aryl hydrocarbon receptor (AHR) is a major xenobiotic receptor that also regulates cell cycle. The purpose of this study was to investigate whether IGF-2 promotes MCF-7 breast cancer proliferation by inducing AHR. Western blot and quantitative real time PCR (Q-PCR) analysis revealed that IGF-2 induced an approximately 2-fold increase (P < .001) in the expression of AHR and CCND1. Chromatin immunoprecipitation (ChIP), followed by Q-PCR indicated that IGF-2 promoted (P < .001) a 7-fold increase in AHR binding on the CCND1 promoter. AHR knockdown significantly (P < .001) inhibited IGF-2 stimulated increases in CCND1 mRNA and protein. AHR knockdown cells were less (P < .001) responsive to the proliferative effects of IGF-2 than control cells. Collectively, our findings have revealed a new regulatory mechanism by which IGF-2 induction of AHR promotes the expression of CCND1 and the proliferation of MCF-7 cells. This previously uncharacterized pathway could be important for the proliferation of IGF responsive cancer cells that also express AHR.

  2. Benzimidazoles diminish ERE transcriptional activity and cell growth in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Payton-Stewart, Florastina [Department of Chemistry, College of Arts and Sciences, Xavier University of Louisiana, New Orleans, LA (United States); Tilghman, Syreeta L. [Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, LA (United States); Williams, LaKeisha G. [Division of Clinical and Administrative Sciences, College of Pharmacy Xavier University of Louisiana, New Orleans, LA (United States); Winfield, Leyte L., E-mail: lwinfield@spelman.edu [Department of Chemistry, Spelman College, Atlanta, GA (United States)

    2014-08-08

    Highlights: • The methyl-substituted benzimidazole was more effective at inhibiting growth in MDA-MB 231 cells. • The naphthyl-substituted benzimidazole was more effective at inhibiting growth in MCF-7 cells than ICI. • The benzimidazole molecules demonstrated a dose-dependent reduction in ERE transcriptional activity. • The benzimidazole molecules had binding mode in ERα and ERβ comparable to that of the co-crystallized ligand. - Abstract: Estrogen receptors (ERα and ERβ) are members of the nuclear receptor superfamily. They regulate the transcription of estrogen-responsive genes and mediate numerous estrogen related diseases (i.e., fertility, osteoporosis, cancer, etc.). As such, ERs are potentially useful targets for developing therapies and diagnostic tools for hormonally responsive human breast cancers. In this work, two benzimidazole-based sulfonamides originally designed to reduce proliferation in prostate cancer, have been evaluated for their ability to modulate growth in estrogen dependent and independent cell lines (MCF-7 and MDA-MB 231) using cell viability assays. The molecules reduced growth in MCF-7 cells, but differed in their impact on the growth of MDA-MB 231 cells. Although both molecules reduced estrogen response element (ERE) transcriptional activity in a dose dependent manner, the contrasting activity in the MDA-MB-231 cells seems to suggest that the molecules may act through alternate ER-mediated pathways. Further, the methyl analog showed modest selectivity for the ERβ receptor in an ER gene expression array panel, while the naphthyl analog did not significantly alter gene expression. The molecules were docked in the ligand binding domains of the ERα-antagonist and ERβ-agonist crystal structures to evaluate the potential of the molecules to interact with the receptors. The computational analysis complimented the results obtained in the assay of transcriptional activity and gene expression suggesting that the molecules

  3. Breast Cancer (For Kids)

    Science.gov (United States)

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

  4. Synthetic matrix metalloproteinase inhibitors inhibit growth of established breast cancer osteolytic lesions and prolong survival in mice

    DEFF Research Database (Denmark)

    Winding, Bent; NicAmhlaoibh, Róisín; Misander, Henriette;

    2002-01-01

    Breast cancer frequently leads to incurable bone metastasis. Essential requirements for the development of bone metastasis are cell-cell and cell-matrix interactions, release of bioactive growth factors and cytokines, and removal of large amounts of bone matrix. Matrix metalloproteinases (MMPs...

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

    Directory of Open Access Journals (Sweden)

    Sitti Rahma Abdul Hafid

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

  6. Tumor stromal vascular endothelial growth factor A is predictive of poor outcome in inflammatory breast cancer

    International Nuclear Information System (INIS)

    Inflammatory breast cancer (IBC) is a highly angiogenic disease; thus, antiangiogenic therapy should result in a clinical response. However, clinical trials have demonstrated only modest responses, and the reasons for these outcomes remain unknown. Therefore, the purpose of this retrospective study was to determine the prognostic value of protein levels of vascular endothelial growth factor (VEGF-A), one of the main targets of antiangiogenic therapy, and its receptors (VEGF-R1 and -R2) in IBC tumor specimens. Specimens from IBC and normal breast tissues were obtained from Algerian patients. Tumor epithelial and stromal staining of VEGF-A, VEGF-R1, and VEGF-R2 was evaluated by immunohistochemical analysis in tumors and normal breast tissues; this expression was correlated with clinicopathological variables and breast cancer-specific survival (BCSS) and disease-free survival (DFS) duration. From a set of 117 IBC samples, we evaluated 103 ductal IBC tissues and 25 normal specimens. Significantly lower epithelial VEGF-A immunostaining was found in IBC tumor cells than in normal breast tissues (P <0.01), cytoplasmic VEGF-R1 and nuclear VEGF-R2 levels were slightly higher, and cytoplasmic VEGF-R2 levels were significantly higher (P = 0.04). Sixty-two percent of IBC tumors had high stromal VEGF-A expression. In univariate analysis, stromal VEGF-A levels predicted BCSS and DFS in IBC patients with estrogen receptor-positive (P <0.01 for both), progesterone receptor-positive (P = 0.04 and P = 0.03), HER2+ (P = 0.04 and P = 0.03), and lymph node involvement (P <0.01 for both). Strikingly, in a multivariate analysis, tumor stromal VEGF-A was identified as an independent predictor of poor BCSS (hazard ratio [HR]: 5.0; 95% CI: 2.0-12.3; P <0.01) and DFS (HR: 4.2; 95% CI: 1.7-10.3; P <0.01). To our knowledge, this is the first study to demonstrate that tumor stromal VEGF-A expression is a valuable prognostic indicator of BCSS and DFS at diagnosis and can therefore be used to

  7. Anti-epidermal growth factor receptor conjugated mesoporous zinc oxide nanofibers for breast cancer diagnostics.

    Science.gov (United States)

    Ali, Md Azahar; Mondal, Kunal; Singh, Chandan; Malhotra, Bansi Dhar; Sharma, Ashutosh

    2015-04-28

    We report the fabrication of an efficient, label-free, selective and highly reproducible immunosensor with unprecedented sensitivity (femto-molar) to detect a breast cancer biomarker for early diagnostics. Mesoporous zinc oxide nanofibers (ZnOnFs) are synthesized by electrospinning technique with a fiber diameter in the range of 50-150 nm. Fragments of ZnOnFs are electrophoretically deposited on an indium tin oxide glass substrate and conjugated via covalent or electrostatic interactions with a biomarker (anti-ErbB2; epidermal growth factor receptor 2). Oxygen plasma treatment of the carbon doped ZnOnFs generates functional groups (-COOH, -OH, etc.) that are effective for the conjugation of anti-ErbB2. ZnOnFs without plasma treatment that conjugate via electrostatic interactions were also tested for comparison. Label-free detection of the breast cancer biomarker by this point-of-care device is achieved by an electrochemical impedance technique that has high sensitivity (7.76 kΩ μM(-1)) and can detect 1 fM (4.34 × 10(-5) ng mL(-1)) concentration. The excellent impedimetric response of this immunosensor provides a fast detection (128 s) in a wide detection test range (1.0 fM-0.5 μM). The oxy-plasma treated ZnOnF immunoelectrode shows a higher association constant (404.8 kM(-1) s(-1)) indicating a higher affinity towards the ErbB2 antigen compared to the untreated ZnOnF immunoelectrode (165.6 kM(-1) s(-1)). This sensor is about an order of magnitude more sensitive than the best demonstrated in the literature based on different nanomaterials and about three orders of magnitude better than the ELISA standard for breast cancer biomarker detection. This proposed point-of-care cancer diagnostic offers several advantages, such as higher stability, rapid monitoring, simplicity, cost-effectiveness, etc., and should prove to be useful for the detection of other bio- and cancer markers. PMID:25811908

  8. Growth rate and characteristics of breast cancers detected by ultrasonography screening

    International Nuclear Information System (INIS)

    Breast cancer screening was carried out at our institution in a ''Human Dock'' style health check, by inspection and palpation, together with ultrasonography. Breast cancers detected were reviewed and the utility of ultrasonography was evaluated. A total of 14,063 women underwent the screening and the results were good, with a recall rate of 3.4%, a cancer detection rate of 0.30%, and a positive predictive value of 8.7%. Of 42 breast cancers detected by ultrasonography, 30 (71%) were 1.5 cm or less in diameter. For breast cancers detected by inspection and palpation, the detection rate for small cancers measuring 1.5 cm or less was 33% (10 out of 30 women), and 100% (12 women) for tumors measuring more than 1.5 cm. The cancer detection rate by mammography was 39% (9 out of 23 cancers) for tumors measuring 1.5 cm or less, and 91% (10 out of 11 cases) for those larger than 1.5 cm. Thus cancer detection by ultrasonography was optimal for tumors measuring 1.5 cm or less. Histologically proven lymph node metastasis was positive in 8 (25%) of 32 patients, among whom some had primary cancers measuring 1.5 cm or less. Tumor volume doubling time (TVDT) was measurable in 10 women; there was no change in size in one instance, and in the others TVDT was 4.8 to 32.5 months (mean 15.5 months), small cancers approximately 1 cm in size having a long TVDT. In women whose cancer size could be determined twice or more, TVDT tended to be short when a cancer measured about 1 cm or more. Cancers with a long TVDT showed low histological malignancy, and thus detection of breast cancers with a long TVDT at screening appears to be rewarding. (author)

  9. Premenopausal Obesity and Breast Cancer Growth Rates in a Rodent Model

    OpenAIRE

    Matthews, Shawna B.; McGinley, John N.; Neil, Elizabeth S.; Thompson, Henry J.

    2016-01-01

    Obese premenopausal women with breast cancer have poorer prognosis for long term survival, in part because their tumors are larger at the time of diagnosis than are found in normal weight women. Whether larger tumor mass is due to obesity-related barriers to detection or to effects on tumor biology is not known. This study used polygenic models for obesity and breast cancer to deconstruct this question with the objective of determining whether cell autonomous mechanisms contribute to the link...

  10. Curcumin induces apoptosis in breast cancer cells and inhibits tumor growth in vitro and in vivo

    OpenAIRE

    Lv, Zhi-Dong; Liu, Xiang-Ping; Zhao, Wei-Jun; Dong, Qian; Li, Fu-Nian; Wang, Hai-Bo; Kong, Bin

    2014-01-01

    Curcumin has shown therapeutic and/or adjuvant therapeutic effects on the treatment of some patients with breast cancer. However, its mechanisms of action are largely unknown. This study was designed to investigate its antitumor effect and underlying mechanisms in human breast cancer MDA-MB-231 and MCF-7 cells. The MTT assay was used to evaluate cell viability, and flow cytometry, acridine orange staining and transmission electron microscopy were used to detect apoptosis for cultured cells. T...

  11. Control of the growth of human breast cancer cells in culture by manipulation of arachidonate metabolism

    International Nuclear Information System (INIS)

    Arachidonate metabolites are important regulators of human breast cancer cells. Production of bioactive lipids are frequently initiated by the enzyme phospholipase A2 which releases arachidonic acid (AA) that is rapidly metabolized by cyclooxygenases (COX) or lipoxygenases (LO) to other highly potent lipids. In this study we screened a number of inhibitors which blocked specific pathways of AA metabolism for their antiproliferative activity on MCF-7 wild type and MCF-7 ADR drug resistant breast cancer cells. The toxicity of these inhibitors was further tested on human bone marrow cell proliferation. Inhibitors of LO pathways (specifically the 5-LO pathway) were most effective in blocking proliferation. Inhibitors of platelet activating factor, a byproduct of arachidonate release, were also effective antiproliferative agents. Curcumin, an inhibitor of both COX and LO pathways of eicosanoid metabolism, was 12-fold more effective in blocking proliferation of the MCF-7 ADRs cells compared to MCF-7 wild type (WT) cells. These inhibitors that effectively blocked the proliferation of breast cancer cells showed varying degrees of toxicity to cultures of human bone marrow cells. We observed greater toxicity to bone marrow cells with inhibitors that interfere with the utilization of AA in contrast to those which block utilization of its downstream metabolites. MK-591, MK-886, PCA-4248, and AA-861 blocked proliferation of breast cancer cells but showed no toxicity to bone marrow cells. These inhibitors were effective in blocking the proliferation of breast cancer cells and may be potentially useful in human breast cancer therapy

  12. Biochanin A Modulates Cell Viability, Invasion, and Growth Promoting Signaling Pathways in HER-2-Positive Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Vikas Sehdev

    2009-01-01

    Full Text Available Overexpression of HER-2 receptor is associated with poor prognosis and aggressive forms of breast cancer. Scientific literature indicates a preventive role of isoflavones in cancer. Since activation of HER-2 receptor initiates growth-promoting events in cancer cells, we studied the effect of biochanin A (an isoflavone on associated signaling events like receptor activation, downstream signaling, and invasive pathways. HER-2-positive SK-BR-3 breast cancer cells, MCF-10A normal breast epithelial cells, and NIH-3T3 normal fibroblast cells were treated with biochanin A (2–100 μM for 72 hours. Subsequently cell viability assay, western blotting and zymography were carried out. The data indicate that biochanin A inhibits cell viability, signaling pathways, and invasive enzyme expression and activity in SK-BR-3 cancer cells. Biochanin A did not inhibit MCF-10A and NIH-3T3 cell viability. Therefore, biochanin A could be a unique natural anticancer agent which can selectively target cancer cells and inhibit multiple signaling pathways in HER-2-positive breast cancer cells.

  13. Advances in Variations of Estrogen Receptor, Progesterone Receptor and Human Epidermal Growth Factor Receptor-2 Status in Metastatic Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Yuan Yuan; Zhang Lili

    2013-01-01

    Chemotherapy, endocrine therapy and molecular targeted therapy are vital means in the treatment of metastatic breast cancer (MBC), whose reasonable and standard applications are of great importance to prolong patients’ survival and improve the quality of life. The expressions of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) present signiifcant differences between primary and metastatic breast cancer. However, these differences may affect the selection of MBC patients for therapeutic strategies and judgment on the prognosis. Hence, the relevant researches on variations of hormone receptors and HER-2 in primary and metastatic breast cancer, discordant causes of ER, PR and HER-2 expression in primary and metastatic lesions and clinical value of biopsy to the metastases are reviewed in the study.

  14. Epidermal growth factor suppresses induction by progestin of the adhesion protein desmoplakin in T47D breast cancer cells

    International Nuclear Information System (INIS)

    Although the effects of progesterone on cell cycle progression are well known, its role in spreading and adhesion of breast cancer cells has not attracted much attention until recently. Indeed, by controlling cell adhesion proteins, progesterone may play a direct role in breast cancer invasion and metastasis. Progesterone has also been shown to modulate epidermal growth factor (EGF) effects in neoplasia, although EGF effects on progesterone pathways and targets are less well understood. In the present study we identify an effect of EGF on a progesterone target, namely desmoplakin. Initially flow cytometry was used to establish the growing conditions and demonstrate that the T47D breast cancer cell line was responding to progesterone and EGF in a classical manner. Differential display RT-PCR was employed to identify differentially expressed genes affected by progesterone and EGF. Western and Northern blotting were used to verify interactions between EGF and progesterone in three breast cancer cell lines: T47D, MCF-7, and ZR-75. We found the cell adhesion protein desmoplakin to be upregulated by progesterone – a process that was suppressed by EGF. This appears to be a general but not universal effect in breast cancer cell lines. Our findings suggest that progesterone and EGF may play opposing roles in metastasis. They also suggest that desmoplakin may be a useful biomarker for mechanistic studies designed to analyze the crosstalk between EGF and progesterone dependent events. Our work may help to bridge the fields of metastasis and differentiation, and the mechanisms of steroid action

  15. Cytosolic phospholipase A2 activation correlates with HER2 overexpression and mediates estrogen-dependent breast cancer cell growth.

    LENUS (Irish Health Repository)

    Caiazza, Francesco

    2010-05-01

    Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) catalyzes the hydrolysis of membrane glycerol-phospholipids to release arachidonic acid as the first step of the eicosanoid signaling pathway. This pathway contributes to proliferation in breast cancer, and numerous studies have demonstrated a crucial role of cyclooxygenase 2 and prostaglandin E(2) release in breast cancer progression. The role of cPLA(2)alpha activation is less clear, and we recently showed that 17beta-estradiol (E2) can rapidly activate cPLA(2)alpha in MCF-7 breast cancer cells. Overexpression or gene amplification of HER2 is found in approximately 30% of breast cancer patients and correlates with a poor clinical outcome and resistance to endocrine therapy. This study reports the first evidence for a correlation between cPLA(2)alpha enzymatic activity and overexpression of the HER2 receptor. The activation of cPLA(2)alpha in response to E2 treatment was biphasic with the first phase dependent on trans-activation through the matrix metalloproteinase-dependent release of heparin-bound epidermal growth factor. EGFR\\/HER2 heterodimerization resulted in downstream signaling through the ERK1\\/2 cascade to promote cPLA(2)alpha phosphorylation at Ser505. There was a correlation between HER2 and cPLA(2)alpha expression in six breast cancer cell lines examined, and inhibition of HER2 activation or expression in the SKBR3 cell line using herceptin or HER2-specific small interfering RNA, respectively, resulted in decreased activation and expression of cPLA(2)alpha. Pharmacological blockade of cPLA(2)alpha using a specific antagonist suppressed the growth of both MCF-7 and SKBR3 cells by reducing E2-induced proliferation and by stimulating cellular apoptosis and necrosis. This study highlights cPLAalpha(2) as a potential target for therapeutic intervention in endocrine-dependent and endocrine-independent breast cancer.

  16. Breast Cancer Rates by State

    Science.gov (United States)

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

  17. Your Body After Breast Cancer

    Science.gov (United States)

    ... Breast Cancer , Coping with Cancer Your Body After Breast Cancer Article date: September 28, 2012 By Melissa Weber ... age 24, she was diagnosed with stage 3 breast cancer in 2010. “I had no control over what ...

  18. Docetaxel-loaded solid lipid nanoparticles suppress breast cancer cells growth with reduced myelosuppression toxicity

    Directory of Open Access Journals (Sweden)

    Yuan Q

    2014-10-01

    Full Text Available Qing Yuan,1 Jing Han,1,2 Wenshu Cong,1 Ying Ge,3 Dandan Ma,1,3,4 Zhaoxia Dai,3,4 Yaping Li,5 Xiaolin Bi1,3,4 1CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 2School of Life Sciences, Anhui University, Hefei, 3Cancer Center, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 4Graduate School, Dalian Medical University, Dalian, 5Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China Abstract: Docetaxel is an adjuvant chemotherapy drug widely used to treat multiple solid tumors; however, its toxicity and side effects limit its clinical efficacy. Herein, docetaxel-loaded solid lipid nanoparticles (DSNs were developed to reduce systemic toxicity of docetaxel while still keeping its anticancer activity. To evaluate its anticancer activity and toxicity, and to understand the molecular mechanisms of DSNs, different cellular, molecular, and whole genome transcription analysis approaches were utilized. The DSNs showed lower cytotoxicity compared with the commercial formulation of docetaxel (Taxotere® and induced more apoptosis at 24 hours after treatment in vitro. DSNs can cause the treated cancer cells to arrest in the G2/M phase in a dose-dependent manner similar to Taxotere. They can also suppress tumor growth very effectively in a mice model with human xenograft breast cancer. Systemic analysis of gene expression profiles by microarray and subsequent verification experiments suggested that both DSNs and Taxotere regulate gene expression and gene function, including DNA replication, DNA damage response, cell proliferation, apoptosis, and cell cycle regulation. Some of these genes expressed differentially at the protein level although their messenger RNA expression level was similar under Taxotere and DSN treatment. Moreover, DSNs improved the main side effect of Taxotere by greatly

  19. Mechanisms underlying the growth inhibitory effects of the cyclo-oxygenase-2 inhibitor celecoxib in human breast cancer cells

    OpenAIRE

    Basu, Gargi D; Pathangey, Latha B; Tinder, Teresa L; Gendler, Sandra J.; Mukherjee, Pinku

    2005-01-01

    Introduction Inhibitors of cyclo-oxygenase (COX)-2 are being extensively studied as anticancer agents. In the present study we evaluated the mechanisms by which a highly selective COX-2 inhibitor, celecoxib, affects tumor growth of two differentially invasive human breast cancer cell lines. Methods MDA-MB-231 (highly invasive) and MDA-MB-468 (moderately invasive) cell lines were treated with varying concentrations of celecoxib in vitro, and the effects of this agent on cell growth and angioge...

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  1. Anti-epidermal growth factor receptor conjugated mesoporous zinc oxide nanofibers for breast cancer diagnostics

    Science.gov (United States)

    Ali, Md. Azahar; Mondal, Kunal; Singh, Chandan; Dhar Malhotra, Bansi; Sharma, Ashutosh

    2015-04-01

    We report the fabrication of an efficient, label-free, selective and highly reproducible immunosensor with unprecedented sensitivity (femto-molar) to detect a breast cancer biomarker for early diagnostics. Mesoporous zinc oxide nanofibers (ZnOnFs) are synthesized by electrospinning technique with a fiber diameter in the range of 50-150 nm. Fragments of ZnOnFs are electrophoretically deposited on an indium tin oxide glass substrate and conjugated via covalent or electrostatic interactions with a biomarker (anti-ErbB2; epidermal growth factor receptor 2). Oxygen plasma treatment of the carbon doped ZnOnFs generates functional groups (-COOH, -OH, etc.) that are effective for the conjugation of anti-ErbB2. ZnOnFs without plasma treatment that conjugate via electrostatic interactions were also tested for comparison. Label-free detection of the breast cancer biomarker by this point-of-care device is achieved by an electrochemical impedance technique that has high sensitivity (7.76 kΩ μM-1) and can detect 1 fM (4.34 × 10-5 ng mL-1) concentration. The excellent impedimetric response of this immunosensor provides a fast detection (128 s) in a wide detection test range (1.0 fM-0.5 μM). The oxy-plasma treated ZnOnF immunoelectrode shows a higher association constant (404.8 kM-1 s-1) indicating a higher affinity towards the ErbB2 antigen compared to the untreated ZnOnF immunoelectrode (165.6 kM-1 s-1). This sensor is about an order of magnitude more sensitive than the best demonstrated in the literature based on different nanomaterials and about three orders of magnitude better than the ELISA standard for breast cancer biomarker detection. This proposed point-of-care cancer diagnostic offers several advantages, such as higher stability, rapid monitoring, simplicity, cost-effectiveness, etc., and should prove to be useful for the detection of other bio- and cancer markers.We report the fabrication of an efficient, label-free, selective and highly reproducible immunosensor

  2. Breast Cancer In Women Infographic

    Science.gov (United States)

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

  3. Immunohistochemical expression of insulin-like growth factor binding protein-3 in invasive breast cancers and ductal carcinoma in situ: implications for clinicopathology and patient outcome

    OpenAIRE

    Vestey, Sarah B; Perks, Claire M.; Sen, Chandan; Calder, Caroline J; Holly, Jeff MP; Winters, Zoe E

    2004-01-01

    Introduction Insulin-like growth factor binding protein-3 (IGFBP-3) differentially modulates breast epithelial cell growth through insulin-like growth factor (IGF)-dependent and IGF-independent pathways and is a direct (IGF-independent) growth inhibitor as well as a mitogen that potentiates EGF (epidermal growth factor) and interacts with HER-2. Previously, high IGFBP-3 levels in breast cancers have been determined by enzyme-linked immunosorbent assay and immunoradiometric assay methods. In v...

  4. Loss of miR-133a expression associated with poor survival of breast cancer and restoration of miR-133a expression inhibited breast cancer cell growth and invasion

    International Nuclear Information System (INIS)

    miRNAs, endogenous oligonucleotide RNAs, play an important role in mammary gland carcinogenesis and tumor progression. Detection of their expression and investigation of their functions could lead to discovery of novel biomarkers for breast cancer. In situ hybridization was used to detect miR-133a expression in formalin-fixed paraffin-embedded breast surgical specimens from 26 benign, 34 pericancerously normal and 90 cancerous tissues. qRT-PCR was performed to assess miR-133a levels in 6 breast cell lines and 10 benign and 18 cancerous fresh breast tissue specimens. Cell viability, migration, and invasion assays were used to determine the role of miR-133a in regulation of breast cancer cell growth, migration, and invasion, respectively. Luciferase assay was performed to assess miR-133a binding to FSCN1 gene. Expression of miR-133a was reduced from normal through benign to cancerous breast tissues. Expression of miR-133a was also low in breast cancer cell lines. The reduced miR-133a expression was associated with lymph nodes metastasis, high clinical stages, and shorter relapse-free survivals of patients with breast cancer. Furthermore, transfection of miR-133a oligonucleotides slightly inhibited growth but significantly decreased migration and invasion capacity of breast cancer cells, compared with negative controls, whereas knockdown of miR-133a expression induced breast cancer cell migration and invasion. In addition, we identified a putative miR-133a binding site in the 3'-untranslated region (UTR) of Fascin1 (FSCN1) gene using an online bioinformatical tool. We found that miR-133a transfection significantly reduced expression of FSCN1 mRNA and protein. The luciferase reporter assay confirmed that FSCN1 was the direct target gene of miR-133a. miR-133a expression was lost in breast cancer tissues, loss of which was associated with lymph nodes metastasis, high clinical stages and shorter relapse-free survivals of patients with breast cancer. Functionally, mi

  5. Targeting an IKBKE cytokine network impairs triple-negative breast cancer growth

    OpenAIRE

    Barbie, Thanh U.; Alexe, Gabriela; Aref, Amir R.; Li, Shunqiang; Zhu, Zehua; Zhang, Xiuli; Imamura, Yu; Thai, Tran C.; Huang, Ying; Bowden, Michaela; Herndon, John; Cohoon, Travis J.; Fleming, Timothy; Tamayo, Pablo; Mesirov, Jill P.

    2014-01-01

    Triple-negative breast cancers (TNBCs) are a heterogeneous set of cancers that are defined by the absence of hormone receptor expression and HER2 amplification. Here, we found that inducible IκB kinase–related (IKK-related) kinase IKBKE expression and JAK/STAT pathway activation compose a cytokine signaling network in the immune-activated subset of TNBC. We found that treatment of cultured IKBKE-driven breast cancer cells with CYT387, a potent inhibitor of TBK1/IKBKE and JAK signaling, impair...

  6. Oncolytic adenovirus armed with IL-24 Inhibits the growth of breast cancer in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Zhu Wei

    2012-05-01

    Full Text Available Abstract Background Interleukin-24 (IL-24 is a cytokine that belongs to the IL-10 family. It can selectively induce cancer cell apoptosis which has been utilized as a cancer gene therapy strategy. Methods A recombinant type five adenovirus containing IL-24 gene (designated CNHK600-IL24 was constructed, whose replication is activated only in tumor cells. The replication of CNHK600-IL24 in breast tumor cells and fibroblasts were assessed by TCID50 and MTT assay; the secretion of IL-24 was measured by ELISA and western blotting. The in vivo anti-tumor effect of CNHK600-IL24 was investigated in nude mice carrying orthotopic or metastatic breast tumor. Results We observed that CNHK600-IL24 could replicate efficiently and resulted in high level IL-24 expression and massive cell death in human breast cancer cell MDA-MB-231 but not in normal fibroblast cell MRC-5. In addition, orthotopic breast tumor growth in the nude mice model was significantly suppressed when CNHK600-IL24 was administered. In the metastatic model generated by tail vein injection, CNHK600-IL24 virotherapy significantly improved survival compared with the same virus expressing EGFP (median survival CNHK600-IL24, 55 days vs. CNHK600-EGFP, 41 day, p  Conclusion The oncolytic adenovirus armed with IL-24, which exhibited enhanced anti-tumor activity and improved survival, is a promising candidate for virotherapy of breast cancer.

  7. p53 is required for metformin-induced growth inhibition, senescence and apoptosis in breast cancer cells.

    Science.gov (United States)

    Li, Puyu; Zhao, Ming; Parris, Amanda B; Feng, Xiaoshan; Yang, Xiaohe

    2015-09-01

    The p53 tumor repressor gene is commonly mutated in human cancers. The tumor inhibitory effect of metformin on p53-mutated breast cancer cells remains unclear. Data from the present study demonstrated that p53 knockdown or mutation has a negative effect on metformin or phenformin-induced growth inhibition, senescence and apoptosis in breast cancer cells. We also found that p53 reactivating agent nutlin-3α and CP/31398 promoted metformin-induced growth inhibition, senescence and apoptosis in MCF-7 (wt p53) and MDA-MB-231 (mt p53) cells, respectively. Treatment of MCF-7 cells with metformin or phenformin induced increase in p53 protein levels and the transcription of its downstream target genes, Bax and p21, in a dose-dependent manner. Moreover, we demonstrated that AMPK-mTOR signaling played a role in metformin-induced p53 up-regulation. The present study showed that p53 is required for metformin or phenformin-induced growth inhibition, senescence and apoptosis in breast cancer cells. The combination of metformin with p53 reactivating agents, like nutlin-3α and CP/31398, is a promising strategy for improving metformin-mediated anti-cancer therapy, especially for tumors with p53 mutations. PMID:26225749

  8. Inhibition of system L (LAT1/CD98hc) reduces the growth of cultured human breast cancer cells.

    Science.gov (United States)

    Shennan, David B; Thomson, Jean

    2008-10-01

    It has been suggested that system L (LAT1/CD98hc) is up-regulated in cancer cells, including breast tumour cells, and is therefore a promising molecular target to inhibit or limit tumour cell growth. In view of this, we have examined the effect of BCH and other inhibitors of system L on the growth of MCF-7, ZR-75-1 and MDA-MB-231 cells. Treating cells with BCH markedly inhibited the metabolism of WST-1 in a dose-dependent fashion. Similarly, melphalan and D-leucine inhibited the growth of cultured breast cancer cells whereas MeAIB, an inhibitor of system A, was without effect. The effects of BCH and melphalan on cell growth were non-additive suggesting that both compounds were acting at a single locus. The results indicate that system L is required to maintain MCF-7, ZR-75-1 and MDA-MB-231 cell growth and support the notion that LAT1/CD98hc may be a suitable target to inhibit breast cancer progression. PMID:18813831

  9. Prognostic value of insulin-like growth factor 1 and insulin-like growth factor binding protein 3 blood levels in breast cancer.

    NARCIS (Netherlands)

    Hartog, H.; Boezen, H.M.; Jong, M.M. de; Schaapveld, M.; Wesseling, J.; Graaf, W.T.A. van der

    2013-01-01

    High circulating insulin-like growth factor 1 (IGF-1) levels are firmly established as a risk factor for developing breast cancer, especially estrogen positive tumors. The effect of circulating IGF-1 on prognosis once a tumor is established is unknown. The authors explored the effect of IGF-1 blood

  10. Breast Cancer Immunotherapy

    Institute of Scientific and Technical Information of China (English)

    JuhuaZhou; YinZhong

    2004-01-01

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

  11. Breast Cancer Immunotherapy

    Institute of Scientific and Technical Information of China (English)

    Juhua Zhou; Yin Zhong

    2004-01-01

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

  12. Human Sulfatase 2 inhibits in vivo tumor growth of MDA-MB-231 human breast cancer xenografts

    International Nuclear Information System (INIS)

    Extracellular human sulfatases modulate growth factor signaling by alteration of the heparin/heparan sulfate proteoglycan (HSPG) 6-O-sulfation state. HSPGs bind to numerous growth factor ligands including fibroblast growth factors (FGF), epidermal growth factors (EGF), and vascular endothelial growth factors (VEGF), and are critically important in the context of cancer cell growth, invasion, and metastasis. We hypothesized that sulfatase activity in the tumor microenvironment would regulate tumor growth in vivo. We established a model of stable expression of sulfatases in the human breast cancer cell line MDA-MB-231 and purified recombinant human Sulfatase 2 (rhSulf2) for exogenous administration. In vitro studies were performed to measure effects on breast cancer cell invasion and proliferation, and groups were statistically compared using Student's t-test. The effects of hSulf2 on tumor progression were tested using in vivo xenografts with two methods. First, MDA-MB-231 cells stably expressing hSulf1, hSulf2, or both hSulf1/hSulf2 were grown as xenografts and the resulting tumor growth and vascularization was compared to controls. Secondly, wild type MDA-MB-231 xenografts were treated by short-term intratumoral injection with rhSulf2 or vehicle during tumor growth. Ultrasound analysis was also used to complement caliper measurement to monitor tumor growth. In vivo studies were statistically analyzed using Student's t test. In vitro, stable expression of hSulf2 or administration of rhSulf2 in breast cancer cells decreased cell proliferation and invasion, corresponding to an inhibition of ERK activation. Stable expression of the sulfatases in xenografts significantly suppressed tumor growth, with complete regression of tumors expressing both hSulf1 and hSulf2 and significantly smaller tumor volumes in groups expressing hSulf1 or hSulf2 compared to control xenografts. Despite significant suppression of tumor volume, sulfatases did not affect vascular

  13. Early breast cancer

    International Nuclear Information System (INIS)

    Breast cancer remains a common disease throughout the world. Here we review new knowledge about early breast cancer obtained during the past 5 years. The prognosis of early breast cancer is generally favorable. Especially, ductal carcinoma in situ has been regarded as a non-life-threatening disease. Therefore, early diagnosis and early onset of the treatment has been important. Early age at menarche, late age at first birth, and late age at menopause are related to breast cancer risk. Examination by mammography and ultrasonography is still the most effective means of detection for premenopausal and postmenopausal women, respectively. Additionally, there have been important advances in MRI, sentinel lymph node biopsy, breast-conserving surgery, partial breast irradiation, neoadjuvant systemic therapy, and adjuvant systemic therapy. Another approach to keeping the disease under control is the elucidation of breast cancer's molecular biological features. Assessment of potential molecular targets can lead to early diagnosis and molecular targeted treatment. (author)

  14. Peganum harmala L.’s anti-growth effect on a breast cancer cell line

    Directory of Open Access Journals (Sweden)

    Somayeh Hashemi Sheikh Shabani

    2015-12-01

    Full Text Available This research was done to evaluate the induction of apoptosis in MDA-MB-231 breast cancer cell line by Peganum harmala’s extract, in which a significant amount of ß-carbolines is included. The apoptosis incidence was assessed through Annexin-V-Flous kit. The expressions of genes through which intrinsic apoptosis pathway are involved, Bax, Bcl-2, Bid, and Puma, over the genes the expressions of which are linked to extrinsic apoptosis pathway, TRAIL, Caspase8, p21, and p53, were examined by RT-PCR and Real-time PCR. The results demonstrate that the extract decreases the growth rate of the cancer cell line through inducing apoptosis mechanism. As long as the expression of anti-apoptosis Bcl-2 gen reduced dramatically, an over-expression in Bax and Puma genes was monitored indicating activation of intrinsic apoptosis pathway. A notable over-expression observed with TRAIL and Caspase8 genes as well as Bid gene. The latter is an intermediate for both intrinsic and extrinsic pathways of apoptosis.

  15. Breast Cancer Risk in American Women

    Science.gov (United States)

    ... 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 ...

  16. 胰岛素样生长因子-1在乳腺癌组织中的表达%Expression of insulin-like growth factor-1 in breast cancer tissues

    Institute of Scientific and Technical Information of China (English)

    Mingxun Chen; Mengquan Li; Jingruo Li

    2009-01-01

    Objective: We investigated the expression of insulin-like growth factor-1 (IGF-1) so as to explore its relationship with carcinogenesis and development of breast cancer. Methods: IGF-1 mRNA levels in tissues of breast cancer, adjacent breast cancer in 70 cases breast cancer patients were analyzed by RT-PCR with the normal breast tissues of paired breast as the control. Results: The level of IGF-1 mRNA expression in breast cancer tissues was significantly higher than that in the paired adjacent to breast cancer tissues, normal mammary gland tissues. The ration of IGF-1/β-actin were 0.679±0.075, 0.463±0.085, 0.305±0.031, respectively. There was significant difference between different groups (P 0.005). Conclusion: The high-level expression of IGF-1 in breast cancer tissues is correlated with carcinogenesis, development and metastasis of breast cancer.

  17. Risk factors for breast cancer and expression of insulin-like growth factor-2 (IGF-2 in women with breast cancer in Wuhan City, China.

    Directory of Open Access Journals (Sweden)

    Jun Qiu

    Full Text Available PURPOSE: The purpose of this study was to explore the risk factors for breast cancer and establish the expression rate of IGF-2 in female patients. METHODS: A case control study with 500 people in case group and 500 people in control group. A self-administered questionnaire was used to investigate risk factors for breast cancer. All cases were interviewed during a household survey. Immune-histochemical method was used to inspect the expression of IGF-2 in different tissues (benign breast lesions, breast cancer and tumor-adjacent tissue. RESULTS: Multivariate adjusted odds ratios and 95% confidence intervals were calculated using unconditional logistic regression. High body mass index (OR = 1.012,95%CI = 1.008-1.016, working attributes (OR = 1.004, 95%CI = 1.002 = 1.006, long menstrual period (OR = 1.007, 95%CI = 1.005-1.009, high parity OR = 1.003, 95%CI = 1.001-1.005 , frequent artificial abortion (OR = 1.004, 95%CI = 1.001-1.005, family history of cancer (OR = 1.003, 95%CI = 1.000-1.005, period of night shift (OR = 1.003, 95%CI = 1.001-1.006, live in high risk environment (OR = 1.005, 95%CI = 1.002-1.008, and family problems (OR = 1.010, 95%CI = 1.005-1.014 were associated with increased risk for breast cancer. In this study, good sleeping status, positive coping strategies, subjective support, and utility degree of social support were associated with reduced risk for breast cancer (OR = 0.998, 0.997, 0.985, 0.998 respectively; 95%CI = 0.996-1.000, 0.994-1.000, 0.980-0.989, 0.996-1.000, respectively. In benign breast lesions, breast cancer and tumor-adjacent tissue, IGF-2 was mainly expressed in the cytoplasm, but its expression rate was different (p<0.05. CONCLUSIONS: The incidence of breast cancer is a common result of multiple factors. IGF-2 is involved in the development of breast cancer, and its expression varies in different tissues (benign breast lesions

  18. Oxalate induces breast cancer

    OpenAIRE

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

    2015-01-01

    Background 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 l...

  19. Familial breast cancer.

    OpenAIRE

    Phipps, R. F.; Perry, P M

    1988-01-01

    Familial breast cancer is important because of all the known risk factors associated with developing the disease. The one with the most predictability is a positive family history. It is also important because a family history causes anxiety in the families concerned, and young women will often ask their chance of developing the disease. This form of breast cancer accounts for 10% of causes and has factors that distinguish it from the sporadic variety. Relatives of familial breast cancer pati...

  20. Breast cancer stem cells

    OpenAIRE

    Owens, Thomas W.; Naylor, Matthew J.

    2013-01-01

    Cancer metastasis, resistance to therapies and disease recurrence are significant hurdles to successful treatment of breast cancer. Identifying mechanisms by which cancer spreads, survives treatment regimes and regenerates more aggressive tumors are critical to improving patient survival. Substantial evidence gathered over the last 10 years suggests that breast cancer progression and recurrence is supported by cancer stem cells (CSCs). Understanding how CSCs form and how they contribute to th...

  1. Norstictic Acid Inhibits Breast Cancer Cell Proliferation, Migration, Invasion, and In Vivo Invasive Growth Through Targeting C-Met.

    Science.gov (United States)

    Ebrahim, Hassan Y; Elsayed, Heba E; Mohyeldin, Mohamed M; Akl, Mohamed R; Bhattacharjee, Joydeep; Egbert, Susan; El Sayed, Khalid A

    2016-04-01

    Breast cancer is a major health problem affecting the female population worldwide. The triple-negative breast cancers (TNBCs) are characterized by malignant phenotypes, worse patient outcomes, poorest prognosis, and highest mortality rates. The proto-oncogenic receptor tyrosine kinase c-Met is usually dysregulated in TNBCs, contributing to their oncogenesis, tumor progression, and aggressive cellular invasiveness that is strongly linked to tumor metastasis. Therefore, c-Met is proposed as a promising candidate target for the control of TNBCs. Lichens-derived metabolites are characterized by their structural diversity, complexity, and novelty. The chemical space of lichen-derived metabolites has been extensively investigated, albeit their biological space is still not fully explored. The anticancer-guided fractionation of Usnea strigosa (Ach.) lichen extract led to the identification of the depsidone-derived norstictic acid as a novel bioactive hit against breast cancer cell lines. Norstictic acid significantly suppressed the TNBC MDA-MB-231 cell proliferation, migration, and invasion, with minimal toxicity to non-tumorigenic MCF-10A mammary epithelial cells. Molecular modeling, Z'-LYTE biochemical kinase assay and Western blot analysis identified c-Met as a potential macromolecular target. Norstictic acid treatment significantly suppressed MDA-MB-231/GFP tumor growth of a breast cancer xenograft model in athymic nude mice. Lichen-derived natural products are promising resources to discover novel c-Met inhibitors useful to control TNBCs. PMID:26744260

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

    Directory of Open Access Journals (Sweden)

    Hardman W Elaine

    2005-07-01

    Full Text Available Abstract 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 3 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.

  3. Dietary omega-3 fatty acids and ionizing irradiation on human breast cancer xenograft growth and angiogenesis

    Directory of Open Access Journals (Sweden)

    Cameron Ivan L

    2005-04-01

    Full Text Available Abstract Background The effects of an omega-3 (n-3 fatty acid enriched diet alone and in combination with gamma irradiation (IR therapy in nude mice bearing a human MDA-MB231 breast cancer xenograft were tested. The cancer cells were injected into the mammary fat pad of young female mice. Six weeks later, mice were randomly divided into two diet groups: 1 mice with 10% corn oil (rich in omega 6 fatty acids in their food, 2 mice consuming a 10% fat diet that was enriched in n-3 fatty acids. After two weeks on the diet, treatment with 200 cGy of IR every second day for four treatments (total 800 cGy was initiated on half of the mice from each diet group. Some mice in each of the 4 groups were euthanized 24 hours after the end of IR while the remaining mice were followed for 3 additional weeks. Tumor sections were stained for endothelial cells with CD31 and PAS and for hypoxia inducible factor 1α (HIF-α. Results The tumor cortex within 100 microns of the well-vascularized capsule had little vascularization. Blood vessels, capillaries, and endothelial pseudopods were found at areas greater than 100 microns from the capsule (subcortex. Mice on the corn oil diet and treated with IR 24 hours previously or non-irradiated mice fed the n-3 diet had tumors with fewer blood vessels in the subcortex and more endothelial pseudopods projecting into hypoxic (HIF- α positive areas than did mice from the non-irradiated corn oil fed group. The tumor growth rate of mice that received IR or that were fed the n-3 fatty acid enriched diet was significantly slower than in the mice fed the 10% corn oil diet. Harmful side effects were found only in the IR treated mice. Conclusion The omega-3 fatty acid enriched diet proved to be a safe means for retarding tumor growth and vascularization.

  4. FHL2 inhibits the Id3-promoted proliferation and invasive growth of human MCF-7 breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    CHEN Yi-hong; WU Zhi-qiang; ZHAO Ya-li; SI Yi-ling; GUO Ming-zhou; HAN Wei-dong

    2012-01-01

    Background Id3 plays a key role in the progression of breast cancer.Previously,four and a half LIM protein (FHL2) was identified as a repressor of Id family proteins by interacting with them.This study aimed to investigate the effects of FHL2 on the transcriptional regulation and oncogenic activities of Id3 in human breast cancer cells.Methods Cell transfection was performed with SuperFect reagent.Stable transfectants that overexpressed Id3 were obtained by selection on G418.The level of Id3 protein was determined by Western blotting analysis.Dual luciferase assays were used to measure the effect of Id3 and FHL2 on E47-mediated transcriptional activity in MCF-7 human breast cancer cells.The MTT assay was used to measure cell proliferation.The transwell assay was used to measure the invasive capacity of MCF-7 cancer cells.Results Id3 markedly repressed transcription mediated by the basic helix-loop-helix (bHLH) factor E47 in MCF-7 cells.This Id3-mediated repression was effectively antagonized by FHL2.Overexpression of Id3 markedly promoted the proliferation and invasive capacity of MCF-7 cells; however,these effects were significantly suppressed by the overexpression of FHL2.Conclusions FHL2 can inhibit the proliferation and invasive growth of human breast cancer cells by repressing the functional activity of Id3.The functional roles of FHL2-1d3 signaling in the development of human breast cancer need further research.

  5. Breast Cancer Research at NASA

    Science.gov (United States)

    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).

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

    Directory of Open Access Journals (Sweden)

    Christina H Stuelten

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

  7. Molecular genetics of breast cancer progression

    OpenAIRE

    Sigurður Ingvarsson 1956

    1999-01-01

    Somatic changes in the genome of breast cancer cells include amplifications, deletions and gene mutations. Several chromosome regions harboring known oncogenes are found amplified in breast tumors. Despite the high number of chromosome regions deleted in breast tumors the functional relationship to known genes at these locations and cancer growth is mainly undiscovered. Mutations in two tumor suppressor genes (TSG) have been described in a subset of breast carcinomas. These TSG are the TP53, ...

  8. Arsenic Trioxide Inhibits Cell Growth and Induces Apoptosis through Inactivation of Notch Signaling Pathway in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Zhiwei Wang

    2012-08-01

    Full Text Available Arsenic trioxide has been reported to inhibit cell growth and induce apoptotic cell death in many human cancer cells including breast cancer. However, the precise molecular mechanisms underlying the anti-tumor activity of arsenic trioxide are still largely unknown. In the present study, we assessed the effects of arsenic trioxide on cell viability and apoptosis in breast cancer cells. For mechanistic studies, we used multiple cellular and molecular approaches such as MTT assay, apoptosis ELISA assay, gene transfection, RT-PCR, Western blotting, and invasion assays. For the first time, we found a significant reduction in cell viability in arsenic trioxide-treated cells in a dose-dependent manner, which was consistent with induction of apoptosis and also associated with down-regulation of Notch-1 and its target genes. Taken together, our findings provide evidence showing that the down-regulation of Notch-1 by arsenic trioxide could be an effective approach, to cause down-regulation of Bcl-2, and NF-κB, resulting in the inhibition of cell growth and invasion as well as induction of apoptosis. These results suggest that the anti-tumor activity of arsenic trioxide is in part mediated through a novel mechanism involving inactivation of Notch-1 and its target genes. We also suggest that arsenic trioxide could be further developed as a potential therapeutic agent for the treatment of breast cancer.

  9. BRCC2 inhibits breast cancer cell growth and metastasis in vitro and in vivo via downregulating AKT pathway

    OpenAIRE

    Li, X.; Kong, X; Y Wang; Yang, Q.

    2013-01-01

    In our previous study, we demonstrated that the BRCC2 (breast cancer cell 2) gene is a proapoptotic molecule that interacts with Bcl-XL. BRCC2 downregulation is associated with poor disease-free and overall survival in breast cancer. In this study, we aimed to investigate the role of BRCC2 in tumor suppression in breast cancer. In clinical breast cancer samples, we found that BRCC2 expression was significantly downregulated in cancer lesions compared with paired normal breast tissues. By sile...

  10. Herbal Extract SH003 Suppresses Tumor Growth and Metastasis of MDA-MB-231 Breast Cancer Cells by Inhibiting STAT3-IL-6 Signaling

    OpenAIRE

    Youn Kyung Choi; Sung-Gook Cho; Sang-Mi Woo; Yee Jin Yun; Sunju Park; Yong Cheol Shin; Seong-Gyu Ko

    2014-01-01

    Cancer inflammation promotes cancer progression, resulting in a high risk of cancer. Here, we demonstrate that our new herbal extract, SH003, suppresses both tumor growth and metastasis of MDA-MB-231 breast cancer cells via inhibiting STAT3-IL-6 signaling path. Our new herbal formula, SH003, mixed extract from Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii Maximowicz, suppressed MDA-MB-231 tumor growth and lung metastasis in vivo and reduced the viability and metastatic ...

  11. Vascular endothelial growth inhibitor affects the invasion, apoptosis and vascularisation in breast cancer cell line MDA-MB-231

    Institute of Scientific and Technical Information of China (English)

    Gao Yinguang; Ge Zhicheng; Zhang Zhongtao; Bai Zhigang; Ma Xuemei; Wang Yu

    2014-01-01

    Background Breast cancer is one of the most common malignant female diseases worldwide.It is a significant threat to every woman's health.Vascular endothelial growth inhibitor (VEGI) is known to be abundant in endothelial cells.According to previous literature,overexpression of VEGI has been shown to inhibit tumor neovascularisation and progression in cellular and animal models,but there has been limited research on the significance of VEGI in the breast cancer.Methods In our study,cell lines MDA-MB-231 were first constructed in which VEGI mediated by lentivirus over-expressed.The effects of VEGI over-expression on MDA-MB-231 cells were investigated both in vitro and in vivo.The expression of VEGI in the MDA-MB-231 cells after infection of lentivirus was analyzed using real-time PCR and Western blotting.The effect of the biological characteristics of MDA-MB-231 cells was assessed by growth,invasion,adhesion,and migration assay with subcutaneous tumor-bearing nude mice models.Then the growth curves of the subcutaneous tumors were studied.Expressions of VEGI,CD31 and CD34 in the tumors were analyzed by immunohistochemistry and apoptosis was detected by flow cytometry and immunohistochemistry.Results Infection of MDA-MB-231 cells within the lentivirus resulted in approximately a 1 000-fold increase in the expression of VEGI.As can be seen in the invasion,adhesion and migration assay,the over-expression of VEGI can inhibit the ability of MDA-MB-231 cells during migration,adhesion and invasion.The volume of the subcutaneous tumor in the over-expression group was distinctly and significantly less than that of the control groups.Immunohistochemistry analysis of the tumor biopsies cleady showed the expression of VEGI in the over-expression group increased while CD31 and CD34 decreased significantly.In vitro and in vivo,the early apoptosis rate and the apoptosis index were increased within the VEGI over-expression group as compared with the control group.Conclusions Taken

  12. Breast cancer (metastatic)

    OpenAIRE

    Stebbing, Justin; Slater, Sarah; Slevin, Maurice

    2007-01-01

    Median survival from metastatic breast cancer is 12 months without treatment, but young people can survive up to 20 years with the disease, whereas in other metastatic cancers this would be considered very unusual.

  13. Profile of thyroid hormones in breast cancer patients

    OpenAIRE

    Saraiva P.P.; Figueiredo N.B.; Padovani C.R.; Brentani M.M.; Nogueira C.R.

    2005-01-01

    Estrogen involvement in breast cancer has been established; however, the association between breast cancer and thyroid diseases is controversial. Estrogen-like effects of thyroid hormone on breast cancer cell growth in culture have been reported. The objective of the present study was to determine the profile of thyroid hormones in breast cancer patients. Serum aliquots from 26 patients with breast cancer ranging in age from 30 to 85 years and age-matched normal controls (N = 22) were analyze...

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

    Directory of Open Access Journals (Sweden)

    Debbie Liao

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

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

    Science.gov (United States)

    2015-06-23

    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

  16. Paracrine effect of GTP cyclohydrolase and angiopoietin-1 interaction in stromal fibroblasts on tumor Tie2 activation and breast cancer growth.

    Science.gov (United States)

    Chen, Liye; Zeng, Xin; Kleibeuker, Esther; Buffa, Francesca; Barberis, Alessandro; Leek, Russell D; Roxanis, Ioannis; Zhang, Wei; Worth, Andrew; Beech, John S; Harris, Adrian L; Cai, Shijie

    2016-02-23

    Cancer-associated fibroblasts (CAFs) play a key role in promoting tumor growth, acting through complex paracrine regulation. GTP cyclohydrolase (GTPCH) expression for tetrahydrobiopterin synthesis in tumor stroma is implicated in angiogenesis and tumor development. However, the clinical significance of GTPCH expression in breast cancer is still elusive and how GTPCH regulates stromal fibroblast and tumor cell communication remains unknown. We found that GTPCH was upregulated in breast CAFs and epithelia, and high GTPCH RNA was significantly correlated with larger high grade tumors and worse prognosis. In cocultures, GTPCH expressing fibroblasts stimulated breast cancer cell proliferation and motility, cancer cell Tie2 phosphorylation and consequent downstream pathway activation. GTPCH interacted with Ang-1 in stromal fibroblasts and enhanced Ang-1 expression and function, which in turn phosphorylated tumor Tie2 and induced cell proliferation. In coimplantation xenografts, GTPCH in fibroblasts enhanced tumor growth, upregulating Ang-1 and alpha-smooth muscle actin mainly in fibroblast-like cells. GTPCH inhibition resulted in the attenuation of tumor growth and angiogenesis. GTPCH/Ang-1 interaction in stromal fibroblasts and activation of Tie2 on breast tumor cells could play an important role in supporting breast cancer growth. GTPCH may be an important mechanism of paracrine tumor growth and hence a target for therapy in breast cancer. PMID:26814432

  17. Neuroendocrine breast cancer

    OpenAIRE

    Graça, Susana; Esteves, Joana; Costa, Sílvia; Vale, Sílvio; Maciel, Jorge

    2012-01-01

    Neuroendocrine breast cancer is thought to account for about 1% of all breast cancers. This rare type of breast malignancy is more common in older women and presents as a low-grade, slow-growing cancer. The most definitive markers that indicate neuroendocrine carcinoma are the presence of chromogranin, synaptophysin or neuron-specific enolase, in at least 50% of malignant tumour cells. The authors present a case report of an 83-year-old woman, admitted to their institution with right breast l...

  18. Contralateral breast cancer risk

    International Nuclear Information System (INIS)

    The use of breast-conserving treatment approaches for breast cancer has now become a standard option for early stage disease. Numerous randomized studies have shown medical equivalence when mastectomy is compared to lumpectomy followed by radiotherapy for the local management of this common problem. With an increased emphasis on patient involvement in the therapeutic decision making process, it is important to identify and quantify any unforeseen risks of the conservation approach. One concern that has been raised is the question of radiation- related contralateral breast cancer after breast radiotherapy. Although most studies do not show statistically significant evidence that patients treated with breast radiotherapy are at increased risk of developing contralateral breast cancer when compared to control groups treated with mastectomy alone, there are clear data showing the amount of scattered radiation absorbed by the contralateral breast during a routine course of breast radiotherapy is considerable (several Gy) and is therefore within the range where one might be concerned about radiogenic contralateral tumors. While radiation related risks of contralateral breast cancer appear to be small enough to be statistically insignificant for the majority of patients, there may exist a smaller subset which, for genetic or environmental reasons, is at special risk for scatter related second tumors. If such a group could be predicted, it would seem appropriate to offer either special counselling or special prevention procedures aimed at mitigating this second tumor risk. The use of genetic testing, detailed analysis of breast cancer family history, and the identification of patients who acquired their first breast cancer at a very early age may all be candidate screening procedures useful in identifying such at- risk groups. Since some risk mitigation strategies are convenient and easy to utilize, it makes sense to follow the classic 'ALARA' (as low as reasonably

  19. Inflammatory Breast Cancer

    Science.gov (United States)

    ... breast cancer: consensus statement for standardized diagnosis and treatment. Annals of Oncology 2011; 22(3):515-523. [PubMed Abstract] Fouad TM, Kogawa T, Reuben JM, Ueno NT. The role of inflammation in inflammatory breast cancer. Advances in Experimental Medicine and Biology 2014; 816:53-73. [PubMed ...

  20. Synergistic Effect of Cold Atmospheric Plasma and Drug Loaded Core-shell Nanoparticles on Inhibiting Breast Cancer Cell Growth

    Science.gov (United States)

    Zhu, Wei; Lee, Se-Jun; Castro, Nathan J.; Yan, Dayun; Keidar, Michael; Zhang, Lijie Grace

    2016-01-01

    Nano-based drug delivery devices allowing for effective and sustained targeted delivery of therapeutic agents to solid tumors have revolutionized cancer treatment. As an emerging biomedical technique, cold atmospheric plasma (CAP), an ionized non-thermal gas mixture composed of various reactive oxygen species, reactive nitrogen species, and UV photons, shows great potential for cancer treatment. Here we seek to develop a new dual cancer therapeutic method by integrating promising CAP and novel drug loaded core-shell nanoparticles and evaluate its underlying mechanism for targeted breast cancer treatment. For this purpose, core-shell nanoparticles were synthesized via co-axial electrospraying. Biocompatible poly (lactic-co-glycolic acid) was selected as the polymer shell to encapsulate anti-cancer therapeutics. Results demonstrated uniform size distribution and high drug encapsulation efficacy of the electrosprayed nanoparticles. Cell studies demonstrated the effectiveness of drug loaded nanoparticles and CAP for synergistic inhibition of breast cancer cell growth when compared to each treatment separately. Importantly, we found CAP induced down-regulation of metastasis related gene expression (VEGF, MTDH, MMP9, and MMP2) as well as facilitated drug loaded nanoparticle uptake which may aid in minimizing drug resistance-a major problem in chemotherapy. Thus, the integration of CAP and drug encapsulated nanoparticles provides a promising tool for the development of a new cancer treatment strategy. PMID:26917087

  1. Ganodermanontriol (GDNT) exerts its effect on growth and invasiveness of breast cancer cells through the down-regulation of CDC20 and uPA

    International Nuclear Information System (INIS)

    Highlights: ► Ganodermanontriol (GDNT), a Ganoderma mushroom alcohol, inhibits growth of breast cancer cells. ► CDC20 is over-expressed in tumors but not in the tumor surrounding tissue in breast cancer patients. ► GDNT inhibits expression of CDC20 in breast cancer cells. ► GDNT inhibits cell adhesion, cell migration and cell invasion of breast cancer cells. ► GDNT inhibits secretion of uPA and down-regulates expression of uPAR in breast cancer cells. -- Abstract: Ganoderma lucidum is a medicinal mushroom that has been recognized by Traditional Chinese Medicine (TCM). Although some of the direct anticancer activities are attributed to the presence of triterpenes—ganoderic and lucidenic acids—the activity of other compounds remains elusive. Here we show that ganodermanontriol (GDNT), a Ganoderma alcohol, specifically suppressed proliferation (anchorage-dependent growth) and colony formation (anchorage-independent growth) of highly invasive human breast cancer cells MDA-MB-231. GDNT suppressed expression of the cell cycle regulatory protein CDC20, which is over-expressed in precancerous and breast cancer cells compared to normal mammary epithelial cells. Moreover, we found that CDC20 is over-expressed in tumors when compared to the tissue surrounding the tumor in specimens from breast cancer patients. GDNT also inhibited invasive behavior (cell adhesion, cell migration, and cell invasion) through the suppression of secretion of urokinase-plasminogen activator (uPA) and inhibited expression of uPA receptor. In conclusion, mushroom GDNT is a natural agent that has potential as a therapy for invasive breast cancers.

  2. Ganodermanontriol (GDNT) exerts its effect on growth and invasiveness of breast cancer cells through the down-regulation of CDC20 and uPA

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Jiahua; Jedinak, Andrej [Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States); Sliva, Daniel, E-mail: dsliva@iuhealth.org [Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States); Department of Medicine, School of Medicine, Indiana University, Indianapolis, IN (United States); Indiana University Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN (United States)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Ganodermanontriol (GDNT), a Ganoderma mushroom alcohol, inhibits growth of breast cancer cells. Black-Right-Pointing-Pointer CDC20 is over-expressed in tumors but not in the tumor surrounding tissue in breast cancer patients. Black-Right-Pointing-Pointer GDNT inhibits expression of CDC20 in breast cancer cells. Black-Right-Pointing-Pointer GDNT inhibits cell adhesion, cell migration and cell invasion of breast cancer cells. Black-Right-Pointing-Pointer GDNT inhibits secretion of uPA and down-regulates expression of uPAR in breast cancer cells. -- Abstract: Ganoderma lucidum is a medicinal mushroom that has been recognized by Traditional Chinese Medicine (TCM). Although some of the direct anticancer activities are attributed to the presence of triterpenes-ganoderic and lucidenic acids-the activity of other compounds remains elusive. Here we show that ganodermanontriol (GDNT), a Ganoderma alcohol, specifically suppressed proliferation (anchorage-dependent growth) and colony formation (anchorage-independent growth) of highly invasive human breast cancer cells MDA-MB-231. GDNT suppressed expression of the cell cycle regulatory protein CDC20, which is over-expressed in precancerous and breast cancer cells compared to normal mammary epithelial cells. Moreover, we found that CDC20 is over-expressed in tumors when compared to the tissue surrounding the tumor in specimens from breast cancer patients. GDNT also inhibited invasive behavior (cell adhesion, cell migration, and cell invasion) through the suppression of secretion of urokinase-plasminogen activator (uPA) and inhibited expression of uPA receptor. In conclusion, mushroom GDNT is a natural agent that has potential as a therapy for invasive breast cancers.

  3. Diagnosis of breast cancer by tissue analysis

    Institute of Scientific and Technical Information of China (English)

    Debnath Bhattacharyya; Samir Kumar Bandyopadhyay; Tai-hoon Kim

    2013-01-01

    In this paper,we propose a technique to locate abnormal growth of cells in breast tissue and suggest further pathological test,when require.We compare normal breast tissue with malignant invasive breast tissue by a series of image processing steps.Normal ductal epithelial cells and ductal/lobular invasive carcinogenic cells also consider for comparison here in this paper.In fact,features of cancerous breast tissue (invasive) are extracted and analyses with normal breast tissue.We also suggest the breast cancer recognition technique through image processing and prevention by controlling p53 gene mutation to some extent.

  4. Novel STAT3 phosphorylation inhibitors exhibit potent growth-suppressive activity in pancreatic and breast cancer cells.

    Science.gov (United States)

    Lin, Li; Hutzen, Brian; Zuo, Mingxin; Ball, Sarah; Deangelis, Stephanie; Foust, Elizabeth; Pandit, Bulbul; Ihnat, Michael A; Shenoy, Satyendra S; Kulp, Samuel; Li, Pui-Kai; Li, Chenglong; Fuchs, James; Lin, Jiayuh

    2010-03-15

    The constitutive activation of signal transducer and activator of transcription 3 (STAT3) is frequently detected in most types of human cancer where it plays important roles in survival, drug resistance, angiogenesis, and other functions. Targeting constitutive STAT3 signaling is thus an attractive therapeutic approach for these cancers. We have recently developed novel small-molecule STAT3 inhibitors, known as FLLL31 and FLLL32, which are derived from curcumin (the primary bioactive compound of turmeric). These compounds are designed to bind selectively to Janus kinase 2 and the STAT3 Src homology-2 domain, which serve crucial roles in STAT3 dimerization and signal transduction. Here we show that FLLL31 and FLLL32 are effective inhibitors of STAT3 phosphorylation, DNA-binding activity, and transactivation in vitro, leading to the impediment of multiple oncogenic processes and the induction of apoptosis in pancreatic and breast cancer cell lines. FLLL31 and FLLL32 also inhibit colony formation in soft agar and cell invasion and exhibit synergy with the anticancer drug doxorubicin against breast cancer cells. In addition, we show that FLLL32 can inhibit the induction of STAT3 phosphorylation by IFNalpha and interleukin-6 in breast cancer cells. We also show that administration of FLLL32 can inhibit tumor growth and vascularity in chicken embryo xenografts as well as substantially reduce tumor volumes in mouse xenografts. Our findings highlight the potential of these new compounds and their efficacy in targeting pancreatic and breast cancers that exhibit constitutive STAT3 signaling. PMID:20215512

  5. Mechanisms underlying the growth inhibitory effects of the cyclo-oxygenase-2 inhibitor celecoxib in human breast cancer cells

    International Nuclear Information System (INIS)

    Inhibitors of cyclo-oxygenase (COX)-2 are being extensively studied as anticancer agents. In the present study we evaluated the mechanisms by which a highly selective COX-2 inhibitor, celecoxib, affects tumor growth of two differentially invasive human breast cancer cell lines. MDA-MB-231 (highly invasive) and MDA-MB-468 (moderately invasive) cell lines were treated with varying concentrations of celecoxib in vitro, and the effects of this agent on cell growth and angiogenesis were monitored by evaluating cell proliferation, apoptosis, cell cycle arrest, and vasculogenic mimicry. The in vitro results of MDA-MB-231 cell line were further confirmed in vivo in a mouse xenograft model. The highly invasive MDA-MB-231 cells express higher levels of COX-2 than do the less invasive MDA-MB-468 cells. Celecoxib treatment inhibited COX-2 activity, indicated by prostaglandin E2 secretion, and caused significant growth arrest in both breast cancer cell lines. In the highly invasive MDA-MB-231 cells, the mechanism of celecoxib-induced growth arrest was by induction of apoptosis, associated with reduced activation of protein kinase B/Akt, and subsequent activation of caspases 3 and 7. In the less invasive MDA-MB-468 cells, growth arrest was a consequence of cell cycle arrest at the G0/G1 checkpoint. Celecoxib-induced growth inhibition was reversed by addition of exogenous prostaglandin E2 in MDA-MB-468 cells but not in MDA-MB-231 cells. Furthermore, MDA-MB-468 cells formed significantly fewer extracellular matrix associated microvascular channels in vitro than did the high COX-2 expressing MDA-MB-231 cells. Celecoxib treatment not only inhibited cell growth and vascular channel formation but also reduced vascular endothelial growth factor levels. The in vitro findings corroborated in vivo data from a mouse xenograft model in which daily administration of celecoxib significantly reduced tumor growth of MDA-MB-231 cells, which was associated with reduced vascularization and

  6. Synchronous bilateral breast cancer in a male

    OpenAIRE

    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.

  7. CDC Vital Signs: Breast Cancer

    Science.gov (United States)

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

  8. Breast Cancer and Bone Loss

    Science.gov (United States)

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

  9. Breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    MatthewJNaylor

    2013-08-01

    Full Text Available Cancer metastasis, resistance to therapies and disease recurrence are significant hurdles to successful treatment of breast cancer. Identifying mechanisms by which cancer spreads, survives treatment regimes and regenerates more aggressive tumours are critical to improving patient survival. Substantial evidence gathered over the last 10 years suggests that breast cancer progression and recurrence is supported by cancer stem cells (CSCs. Understanding how CSCs form and how they contribute to the pathology of breast cancer will greatly aid the pursuit of novel therapies targeted at eliminating these cells. This review will summarise what is currently known about the origins of breast CSCs, their role in disease progression and ways in which they may be targeted therapeutically.

  10. Skp2 is over-expressed in breast cancer and promotes breast cancer cell proliferation.

    Science.gov (United States)

    Zhang, Wenwen; Cao, Lulu; Sun, Zijia; Xu, Jing; Tang, Lin; Chen, Weiwei; Luo, Jiayan; Yang, Fang; Wang, Yucai; Guan, Xiaoxiang

    2016-05-18

    The F box protein Skp2 is oncogenic. Skp2 and Skp2B, an isoform of Skp2 are overexpressed in breast cancer. However, little is known regarding the mechanism by which Skp2B promotes the occurrence and development of breast cancer. Here, we determined the expression and clinical outcomes of Skp2 in breast cancer samples and cell lines using breast cancer database, and investigated the role of Skp2 and Skp2B in breast cancer cell growth, apoptosis and cell cycle arrest. We obtained Skp2 is significantly overexpressed in breast cancer samples and cell lines, and high Skp2 expression positively correlated with poor prognosis of breast cancer. Both Skp2 and Skp2B could promote breast cancer cell proliferation, inhibit cell apoptosis, change the cell cycle distribution and induce the increased S phase cells and therefore induce cell proliferation in breast cancer cells. Moreover, the 2 isoforms could both suppress PIG3 expression via independent pathways in the breast cancer cells. Skp2 suppressed p53 and inhibited PIG3-induced apoptosis, while Skp2B attenuated the function of PIG3 by inhibiting PHB. Our results indicate that Skp2 and Skp2B induce breast cancer cell development and progression, making Skp2 and Skp2B potential molecular targets for breast cancer therapy. PMID:27111245

  11. Farnesoid X Receptor inhibits tamoxifen-resistant MCF-7 breast cancer cell growth through down-regulation of HER2 expression

    OpenAIRE

    Giordano, Cinzia; Catalano, Stefania; Panza, Salvatore; Vizza, Donatella; Barone, Ines; Bonofiglio, Daniela; Gelsomino, Luca; Rizza, Pietro; Fuqua, Suzanne A. W; Andò, Sebastiano

    2011-01-01

    Tamoxifen (Tam) treatment is a first-line endocrine therapy for estrogen receptor α (ERα) positive breast cancer patients. Unfortunately, resistance frequently occurs and is often related with overexpression of the membrane tyrosine kinase receptor HER2. This is the rationale behind combined treatments with endocrine therapy and novel inhibitors that reduce HER2 expression and signaling and thus inhibit Tam-resistant breast cancer cell growth. In this study we show that activation of Farnesoi...

  12. Activity Assay of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Triple-Negative Breast Cancer Cells Using Peptide-Conjugated Magnetic Beads

    OpenAIRE

    Ghosh, Gargi; Yan, Xiaoliang; Kron, Stephen J.; Palecek, Sean P.

    2013-01-01

    Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with limited treatment options. Epidermal growth factor receptor I (EGFR) has emerged as a promising target in TNBC. Limited success of the EGFR kinase inhibiting small molecules in clinical trials may be attributed in part to inaccuracy in identifying EGFR signatures in patient tumors. In light of the absence of a simple correlation between EGFR expression and its degree of activation, a simple and reliable ...

  13. Soluble vascular endothelial growth factor receptors 2 (sVEGFR-2) and 3 (sVEGFR-3) and breast cancer risk in the Swedish Mammography Cohort

    OpenAIRE

    Harris, Holly; Wolk, Alicja; Larsson, Anders; Vasson, Marie-Paule; Basu, Samar

    2016-01-01

    Vascular endothelial growth factor (VEGF) is a signalling protein that has been established as a contributor to tumor angiogenesis, and expression of VEGF and its soluble receptors (sVEGFR2 and sVEGFR3) have been demonstrated in breast cancer cells. However, no prospective studies have examined the association between prediagnostic sVEGFR levels and breast cancer risk. We conducted a prospective case-control study nested within the Swedish Mammography Cohort examining the association between ...

  14. Exploring the relationship between posttraumatic growth, cognitive processing, psychological distress, and social constraints in a sample of breast cancer patients.

    Science.gov (United States)

    Koutrouli, Natalia; Anagnostopoulos, Fotios; Griva, Fay; Gourounti, Kleanthi; Kolokotroni, Filippa; Efstathiou, Vasia; Mellon, Robert; Papastylianou, Dona; Niakas, Dimitris; Potamianos, Gregory

    2016-01-01

    Posttraumatic growth (the perception of positive life changes after an encounter with a trauma) often occurs among breast cancer patients and can be influenced by certain demographic, medical, and psychosocial parameters. Social constraints on disclosure (the deprivation of the opportunity to express feelings and thoughts regarding the trauma) and the cognitive processing of the disease seem to be involved in the development of posttraumatic growth. Through the present study the authors aim to: investigate the levels of posttraumatic growth in a sample of 202 women with breast cancer in Greece, explore the relationships between posttraumatic growth and particular demographic, medical, and psychosocial variables according to a proposed model, and test the role of social constraints in the relationship between automatic and deliberate cognitive processing of the trauma. The results showed that posttraumatic growth was evident in the majority of the sample and was associated inversely with age at diagnosis (β = -0.174, p reflective rumination (β = 0.323, p = .001). Social constraints were found to moderate the relationship between intrusions and reflective rumination. Implications of the results and suggestions for future research and practice are outlined. PMID:26605785

  15. Novel medicinal mushroom blend suppresses growth and invasiveness of human breast cancer cells.

    Science.gov (United States)

    Jiang, Jiahua; Sliva, Daniel

    2010-12-01

    Mushrooms are an integral part of Traditional Chinese Medicine (TCM), and have been used for millennia to prevent or treat a variety of diseases. Currently mushrooms or their extracts are used globally in the form of dietary supplements. In the present study we have evaluated the anticancer effects of the dietary supplement, MycoPhyto® Complex (MC), a novel medicinal mushroom blend which consists of a blend of mushroom mycelia from the species Agaricus blazei, Cordyceps sinensis, Coriolus versicolor, Ganoderma lucidum, Grifola frondosa and Polyporus umbellatus, and β-1,3-glucan isolated from the yeast, Saccharomyces cerevisiae. Here, we show that MC demonstrates cytostatic effects through the inhibition of cell proliferation and cell cycle arrest at the G2/M phase of highly invasive human breast cancer cells MDA-MB-231. DNA-microarray analysis revealed that MC inhibits expression of cell cycle regulatory genes (ANAPC2, ANAPC2, BIRC5, Cyclin B1, Cyclin H, CDC20, CDK2, CKS1B, Cullin 1, E2F1, KPNA2, PKMYT1 and TFDP1). Moreover, MC also suppresses the metastatic behavior of MDA-MB-231 by the inhibition of cell adhesion, cell migration and cell invasion. The potency of MC to inhibit invasiveness of breast cancer cells is linked to the suppression of secretion of the urokinase plasminogen activator (uPA) from MDA-MB-231 cells. In conclusion, the MC dietary supplement could have potential therapeutic value in the treatment of invasive human breast cancer. PMID:21042722

  16. Dietary omega-3 fatty acids and ionizing irradiation on human breast cancer xenograft growth and angiogenesis

    OpenAIRE

    Cameron Ivan L; Short Nicholas; Sun LuZhe; Hardman W Elaine

    2005-01-01

    Abstract Background The effects of an omega-3 (n-3) fatty acid enriched diet alone and in combination with gamma irradiation (IR) therapy in nude mice bearing a human MDA-MB231 breast cancer xenograft were tested. The cancer cells were injected into the mammary fat pad of young female mice. Six weeks later, mice were randomly divided into two diet groups: 1) mice with 10% corn oil (rich in omega 6 fatty acids) in their food, 2) mice consuming a 10% fat diet that was enriched in n-3 fatty acid...

  17. [Immunotherapy opportunities in breast cancer].

    Science.gov (United States)

    Pusztai, Lajos; Ladányi, Andrea; Székely, Borbála; Dank, Magdolna

    2016-03-01

    The prognostic value of tumor infiltrating lymphocytes in breast cancer has long been recognized by histopathologists. These observations were reaffirmed by recent immunohistochemistry and gene expression profiling studies that also revealed an association between greater chemotherapy sensitivity and extensive lymphocytic infiltration in early stage breast cancers treated with neoadjuvant chemotherapy. These results suggest that local anti-tumor immune response can at least partially control cancer growth and may mediate the antitumor effects of chemotherapy. However, until recently, there was no direct clinical evidence to demonstrate that enhancing anti-tumor immune response could lead to clinical benefit in breast cancer patients. The recent development of clinically effective immune checkpoint inhibitors made it possible to test the therapeutic impact of augmenting the local anti-tumor immune response. Two Phase I clinical trials using single agent anti-PD-1 (MK-3475, pembrolizumab) and anti-PD-L1 (MPDL3280A, atezolizumab) antibodies demonstrated close to 20% tumor response rates in heavily pretreated, metastatic, triple negative breast cancers. The most remarkable feature of the responses was their long duration. Several patients had disease control close to a year, or longer, which has not previously been seen with chemotherapy regimens in this patient population. A large number of clinical trials are currently underway with these and similar drugs in the neoadjuvant, adjuvant and metastatic settings to define the role of this new treatment modality in breast cancer. PMID:26934349

  18. Hormone Therapy for Breast Cancer

    Science.gov (United States)

    ... to stimulate the growth of breast cancer cells: Selective estrogen receptor modulators (SERMs) bind to estrogen receptors , preventing estrogen from binding. Examples of SERMs approved by the FDA are tamoxifen (Nolvadex®), ... called selective serotonin reuptake inhibitors, or SSRIs), inhibit an enzyme ...

  19. S14 protein in breast cancer cells: Direct evidence of regulation by SREBP-1c, superinduction with progestin, and effects on cell growth

    International Nuclear Information System (INIS)

    Most breast cancers exhibit brisk lipogenesis, and require it for growth. S14 is a lipogenesis-related nuclear protein that is overexpressed in most breast cancers. Sterol response element-binding protein-1c (SREBP-1c) is required for induction of lipogenesis-related genes, including S14 and fatty acid synthase (FAS), in hepatocytes, and correlation of SREBP-1c and FAS expression suggested that SREBP-1c drives lipogenesis in tumors as well. We directly tested the hypothesis that SREBP-1c drives S14 expression and mediates lipogenic effects of progestin in T47D breast cancer cells. Dominant-negative SREBP-1c inhibited induction of S14 and FAS mRNAs by progestin, while active SREBP-1c induced without hormone and superinduced in its presence. Changes in S14 mRNA were reflected in protein levels. A lag time and lack of progestin response elements indicated that S14 and FAS gene activation by progestin is indirect. Knockdown of S14 reduced, whereas overexpression stimulated, T47D cell growth, while nonlipogenic MCF10a mammary epithelial cells were not growth-inhibited. These data directly demonstrate that SREBP-1c drives S14 gene expression in breast cancer cells, and progestin magnifies that effect via an indirect mechanism. This supports the prediction, based on S14 gene amplification and overexpression in breast tumors, that S14 augments breast cancer cell growth and survival

  20. Effect of specific silencing of EMMPRIN on the growth and cell cycle distribution of MCF-7 breast cancer cells.

    Science.gov (United States)

    Yang, X Q; Yang, J; Wang, R; Zhang, S; Tan, Q W; Lv, Q; Meng, W T; Mo, X M; Li, H J

    2015-01-01

    The extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is a member of the immunoglobulin family and shows increased expression in tumor cells. We examined the effect of RNAi-mediated EMMPRIN gene silencing induced by lentiviral on the growth and cycle distribution of MCF-7 breast cancer cells. Lentiviral expressing EMMPRIN-short hairpin RNA were packaged to infect MCF-7 cells. The inhibition efficiency of EMMPRIN was validated by real-time fluorescent quantitation polymerase chain reaction and western blotting. The effect of EMMPRIN on cell proliferation ability was detected using the MTT assay and clone formation experiments. Changes in cell cycle were detected by flow cytometry. EMMPRIN-short hairpin RNA-packaged lentiviral significantly down-regulated EMMPRIN mRNA and protein expression, significantly inhibited cell proliferation and in vitro tumorigenicity, and induced cell cycle abnormalities. Cells in the G0/G1 and G2/M phases were increased, while cells in the S phase were decreased after infection of MCF-7 cells for 3 days. The EMMPRIN gene facilitates breast cancer cell malignant proliferation by regulating cell cycle distribution and may be a molecular target for breast cancer gene therapy. PMID:26634540

  1. Pregnancy After Breast Cancer.

    Science.gov (United States)

    Gemignani; Petrek

    1999-05-01

    BACKGROUND: The issue of pregnancy following the diagnosis and treatment of breast cancer is important because the incidence of breast cancer is increasing in women of childbearing age. The fact that many women are delaying childbearing, whether for educational, professional, or personal reasons, increases the number of women who will undergo breast cancer treatment before completing childbearing. METHODS: Data on pregnancy in breast cancer survivors are limited and consist only of retrospective data. This paper reviews the published literature on the influence of subsequent pregnancy on breast cancer, including three recent large-scale population-based studies. RESULTS: The survival of women with breast carcinoma who subsequently become pregnant is not reported to be decreased in any of the published series. However, several biases may be present that justify the concern regarding the conclusions. CONCLUSIONS: Further research on the safety of subsequent pregnancy after breast carcinoma treatment is needed. To address these issues, patients are currently being accrued for a large, prospective, multicenter study of young breast carcinoma patients. PMID:10758557

  2. Soluble vascular endothelial growth factor receptors 2 (sVEGFR-2) and 3 (sVEGFR-3) and breast cancer risk in the Swedish Mammography Cohort

    Science.gov (United States)

    Harris, Holly; Wolk, Alicja; Larsson, Anders; Vasson, Marie-Paule; Basu, Samar

    2016-01-01

    Vascular endothelial growth factor (VEGF) is a signalling protein that has been established as a contributor to tumor angiogenesis, and expression of VEGF and its soluble receptors (sVEGFR2 and sVEGFR3) have been demonstrated in breast cancer cells. However, no prospective studies have examined the association between prediagnostic sVEGFR levels and breast cancer risk. We conducted a prospective case-control study nested within the Swedish Mammography Cohort examining the association between sVEGFR2 and 3 levels and breast cancer risk. The analysis included 69 incident breast cancer cases diagnosed after blood collection and 719 controls. Logistic regression models were used to calculate odds ratios and 95% confidence intervals. After adjustment for breast cancer risk factors, sVEGFR2 levels were associated with breast cancer risk (OR=1.28; 95% CI=1.06-1.56 per 1000 ng/L increase in concentration) while sVEGFR3 levels were not related to such risk (OR=1.00; 95% CI=0.93-1.07). Our results suggest that sVEGFR2 levels may be positively associated with breast cancer risk, however future studies with larger case groups are necessary to confirm this association. PMID:27186332

  3. Soluble vascular endothelial growth factor receptors 2 (sVEGFR-2) and 3 (sVEGFR-3) and breast cancer risk in the Swedish Mammography Cohort.

    Science.gov (United States)

    Harris, Holly; Wolk, Alicja; Larsson, Anders; Vasson, Marie-Paule; Basu, Samar

    2016-01-01

    Vascular endothelial growth factor (VEGF) is a signalling protein that has been established as a contributor to tumor angiogenesis, and expression of VEGF and its soluble receptors (sVEGFR2 and sVEGFR3) have been demonstrated in breast cancer cells. However, no prospective studies have examined the association between prediagnostic sVEGFR levels and breast cancer risk. We conducted a prospective case-control study nested within the Swedish Mammography Cohort examining the association between sVEGFR2 and 3 levels and breast cancer risk. The analysis included 69 incident breast cancer cases diagnosed after blood collection and 719 controls. Logistic regression models were used to calculate odds ratios and 95% confidence intervals. After adjustment for breast cancer risk factors, sVEGFR2 levels were associated with breast cancer risk (OR=1.28; 95% CI=1.06-1.56 per 1000 ng/L increase in concentration) while sVEGFR3 levels were not related to such risk (OR=1.00; 95% CI=0.93-1.07). Our results suggest that sVEGFR2 levels may be positively associated with breast cancer risk, however future studies with larger case groups are necessary to confirm this association. PMID:27186332

  4. Methylxanthines and breast cancer.

    Science.gov (United States)

    Schairer, C; Brinton, L A; Hoover, R N

    1987-10-15

    We investigated the relationship between methylxanthine consumption and breast cancer using data from a case-control study which included 1,510 cases and 1,882 controls identified through a nation-wide breast cancer screening program. There was no evidence of a positive association between methylxanthine consumption and risk of breast cancer. In fact, there was some suggestion of a negative association, particularly in women diagnosed after age 50. In addition, there was no evidence of increased risk with past or recent methylxanthine consumption, or with the consumption of caffeine or specific beverages, most notably brewed or instant caffeinated coffee and tea. PMID:3117709

  5. Antiangiogenic therapy for breast cancer

    DEFF Research Database (Denmark)

    Nielsen, D.L.; Andersson, M.; Andersen, Jon Alexander Lykkegaard;

    2010-01-01

    ABSTRACT: 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...

  6. Antiangiogenic therapy for breast cancer

    DEFF Research Database (Denmark)

    Nielsen, D.L.; Andersson, M.; Andersen, Jon Alexander Lykkegaard;

    2010-01-01

    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......ABSTRACT: 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...

  7. A Study Evaluating INIPARIB in Combination With Chemotherapy to Treat Triple Negative Breast Cancer Brain Metastasis

    Science.gov (United States)

    2016-02-17

    Estrogen Receptor Negative (ER-Negative) Breast Cancer; Progesterone Receptor Negative (PR-Negative) Breast Cancer; Human Epidermal Growth Factor Receptor 2 Negative (HER2-Negative) Breast Cancer; Brain Metastases

  8. Correlation between serum levels of vascular endothelial growth factor-C and sentinel lymph node status in early breast cancer.

    Science.gov (United States)

    Pérez, Diego; Rohde, Alexander; Callejón, Gonzalo; Pérez-Ruiz, Elisabeth; Rodrigo, Isabel; Rivas-Ruiz, Francisco; Ramos, Belen; Medina, Francisco; Villatoro, Rosa; Redondo, Maximino; Zarcos, Irene; Maañón, Claudio; Rueda, Antonio

    2015-12-01

    Axillary lymph nodes status is the most important prognosis factor in early breast cancer. This status is known by a selective sentinel lymph node biopsy (SLNB) and/or lymphadenectomy. Immunohistochemical studies of breast cancer tumour tissue have reported a relation between the increased expression of vascular endothelial growth factor-C (VEGF-C) and the risk of lymph node metastasis. We researched whether serum levels of VEGF-C could be a predictor factor of sentinel lymph node status in these patients. A prospective analysis was performed on serum from 174 patients with early breast cancer who underwent SLNB. The level of VEGF-C was determined by enzyme-linked immunosorbent assay. Clinical-pathologic variables were collected. Univariate analysis and multivariate logistic regression were conducted, taking SLNB positivity as the segmentation variable. The predictive value of VEGF-C was assessed using ROC curves. Of the sample group of 167 patients, 64 (38.3 %) had affected lymph node. Eighteen patients (28.1 %) presented micrometastasis; there were isolated tumour cells in 11 cases (17.2 %) and macrometastasis in 35 (54.6 %). The median value of VEGF-C was 6561.5 pg/ml. These values did not correlate with any clinical variables, and there was no association between the level of VEGF-C and SLNB status (p = 0.626). In the multivariate analysis, tumour size (p = 0.009) and the presence of vascular invasion (p < 0.001) were independently associated with sentinel lymph node affected. Serum levels of VEGF-C do not appear to predict sentinel lymph node status in patients with early breast cancer who undergo SLNB. PMID:26104766

  9. Decreased expression of the mannose 6- phosphate/insulin-like growth factor-II receptor promotes growth of human breast cancer cells

    International Nuclear Information System (INIS)

    Loss or mutation of the mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGF2R) has been found in breast cancer. However, whether or not decreased levels of functional M6P/IGF2R directly contribute to the process of carcinogenesis needs to be further verified by functional studies. In this study, using viral and ribozyme strategies we reduced the expression of M6P/IGF2R in human breast cancer cells and then examined the effect on growth and apoptosis of these cells. Our results showed that infection of MCF-7 cells with the adenovirus carrying a ribozyme targeted against the M6P/IGF2R mRNA dramatically reduced the level of transcripts and the functional activity of M6P/IGF2R in these cells. Accordingly, cells treated with the ribozyme exhibited a higher growth rate and a lower apoptotic index than control cells (infected with a control vector). Furthermore, decreased expression of M6P/IGF2R enhanced IGF-II-induced proliferation and reduced cell susceptibility to TNF-induced apoptosis. These results suggest that M6P/IGF2R functions as a growth suppressor and its loss or mutation may contribute to development and progression of cancer. This study also demonstrates that adenoviral delivery of the ribozyme provides a useful tool for investigating the role of M6P/IGF2R in regulation of cell growth

  10. Docosahexaenoic Acid in Preventing Recurrence in Breast Cancer Survivors

    Science.gov (United States)

    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

  11. PDK1 promotes tumor growth and metastasis in a spontaneous breast cancer model.

    Science.gov (United States)

    Du, J; Yang, M; Chen, S; Li, D; Chang, Z; Dong, Z

    2016-06-23

    Because malignant cells have altered, usually accelerated, energy consumption, targeting metabolic signaling represents a prevailing strategy for tumor therapy. Phosphoinositide-dependent kinase 1 (PDK1) is a proximal signaling molecule of phosphatidylinositol 3-kinase, which is required for metabolic activation. It is still lacking definitive evidence whether inactivation of PDK1 can overwhelm tumorigenesis in vivo. Herein we revealed that mammary-specific ablation of PDK1 could delay tumor initiation, progression and metastasis in a spontaneous mouse tumor model. We also demonstrated that inducible deletion of PDK1 could noticeably shrink the growing breast tumors. However, a small portion of PDK1-deficient tumorigenic cells eventually established tumor lesions, albeit at a relatively later phase, most likely owing to compensatory upregulation of extracellular signal-regulated kinase 1/2 (Erk1/2) phosphorylation. Consequently, simultaneous inhibition of PDK1 and Erk1/2 impeded the survival of breast cancer cells. Thus we identify PDK1 as a potential therapeutic target for breast cancer, particularly in combination with an Erk1/2 inhibitor. PMID:26455327

  12. San Huang Decoction downregulates Aurora kinase A to inhibit breast cancer cell growth and enhance chemosenstivity to anti-tumor drugs.

    Science.gov (United States)

    Xu, Yanlei; Chen, Xu; Chen, Xiyan; Bian, Weihe; Yao, Chang; Zhang, Xiaoqing; Zhu, Xiaoshu; Chen, Jiajing; Ye, Xiaozhou

    2016-08-01

    Our study aimed to explore whether San Huang Decoction (SHD) inhibited the development of breast cancer by regulating Aurora A. Human breast cancer cell lines MCF-7 and MDA-MB-231 were cultured and SHD extract was prepared. Cell growth assay and apoptosis analysis were respectively performed to detect the effects of SHD on breast cancer cells. In addition, the effects of SHD on the expression of Aurora A and p53 were determined by RT-PCR and western blot. Besides, we used Aurora A siRNA to knock down Aurora A. We then co-administrated SHD and tamoxifen or epirubicin to detect the effect of SHD on chemosensitivity to tamoxifen or epirubicin. SHD treatment significantly inhibited cell growth in a dose-dependent manner. Moreover, SHD treatment resulted in a marked decrease in Aurora A expression and obvious increase in p53 expression. In addition, knockdown of Aurora A induced cell growth inhibition, which was similar to the effect of SHD treatment. Besides, SHD exerted an additive effect on cell growth inhibition and apoptosis induction when breast cancer cells were co-administration of SHD with tamoxifen or epirubicin. Our study indicates that SHD treatment may inhibit cell growth and enhance chemosenstivity to other anti-tumor drugs in breast cancer via down-regulation of Aurora A. PMID:27461831

  13. A peptide derived from α-fetoprotein prevents the growth of estrogen-dependent human breast cancers sensitive and resistant to tamoxifen

    OpenAIRE

    James A. Bennett; Mesfin, Fassil B.; Andersen, Thomas T.; Gierthy, John F.; Jacobson, Herbert I.

    2002-01-01

    An 8-mer peptide (EMTOVNOG) derived from α-fetoprotein was compared with tamoxifen for activity against growth of human breast cancer xenografts implanted in immune-deficient mice. Both peptide and tamoxifen prevented growth of estrogen-receptor-positive MCF-7 and T47D human breast cancer xenografts. A subline of MCF-7, made resistant to tamoxifen by a 6-month exposure to this drug in culture, was found to be resistant to tamoxifen in vivo. Peptide completely prevented the xenograft growth of...

  14. Broccoli Sprout Extract in Treating Patients With Breast Cancer

    Science.gov (United States)

    2016-02-18

    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

  15. The phenomenon of acquired resistance to metformin in breast cancer cells: The interaction of growth pathways and estrogen receptor signaling.

    Science.gov (United States)

    Scherbakov, Alexander M; Sorokin, Danila V; Tatarskiy, Victor V; Prokhorov, Nikolay S; Semina, Svetlana E; Berstein, Lev M; Krasil'nikov, Mikhail A

    2016-04-01

    Metformin, a biguanide antidiabetic drug, is used to decrease hyperglycemia in patients with type 2 diabetes. Recently, the epidemiological studies revealed the potential of metformin as an anti-tumor drug for several types of cancer, including breast cancer. Anti-tumor metformin action was found to be mediated, at least in part, via activation of adenosine monophosphate-activated protein kinase (AMPK)-intracellular energy sensor, which inhibits the mammalian target of rapamycin (mTOR) and some other signaling pathways. Nevertheless, some patients can be non-sensitive or resistant to metformin action. Here we analyzed the mechanism of the formation of metformin-resistant phenotype in breast cancer cells and its role in estrogen receptor (ER) regulation. The experiments were performed on the ER-positive MCF-7 breast cancer cells and metformin-resistant MCF-7 subline (MCF-7/M) developed due to long-term metformin treatment. The transcriptional activity of NF-κB and ER was measured by the luciferase reporter gene analysis. The protein expression was determined by immunoblotting (Snail1, (phospho)AMPK, (phospho)IκBα, (phospho)mTOR, cyclin D1, (phospho)Akt and ERα) and immunohistochemical analysis (E-cadherin). We have found that: 1) metformin treatment of MCF-7 cells is accompanied with the stimulation of AMPK and inhibition of growth-related proteins including IκBα, NF-κB, cyclin D1 and ERα; 2) long-term metformin treatment lead to the appearance and progression of cross-resistance to metformin and tamoxifen; the resistant cells are characterized with the unaffected AMPK activity, but the irreversible ER suppression and constitutive activation of Akt/Snail1 signaling; 3) Akt/Snail1 signaling is involved into progression of metformin resistance. The results presented may be considered as the first evidence of the progression of cross-resistance to metformin and tamoxifen in breast cancer cells. Importantly, the acquired resistance to both drugs is based on the

  16. Living Beyond Breast Cancer

    Science.gov (United States)

    ... Prosthesis Complementary Therapy Types of Complementary Therapy Acupuncture Art Therapy Diet, Nutrition and Exercise Expressive Writing Guided ... SIGN UP FOR OUR MAILING LIST SIGN UP Facebook Twitter Instagram YouTube Living Beyond Breast Cancer Conference ...

  17. Breast Cancer Prevention

    Science.gov (United States)

    ... the risk of breast cancer: Having an abortion. Making diet changes such as eating less fat or more ... does not give formal guidelines or recommendations for making decisions about health care. Reviewers and Updates Editorial Boards ...

  18. Preeclampsia and breast cancer

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: In parous women preeclampsia has been associated with reduced risk of developing breast cancer. Characteristics of births following preeclamptic pregnancies may help understand mechanisms involved in the breast cancer risk reduction inferred by preeclampsia. METHODS: We conducted...... a register-based cohort study of all Danish women giving birth during 1978-2010 (n = 778,701). The association between preeclampsia and breast cancer was evaluated overall and according to birth characteristics by means of incidence rate ratios (IRR) estimated in Poisson regression models. RESULTS: Compared...... with women with non-preeclamptic pregnancies only, women with one or more preeclamptic pregnancies were 19% significantly less likely to develop breast cancer (IRR = 0.81 [95% CI 0.72-0.93]). We found some indication of greater risk reduction in women with term births, one or more previous births...

  19. Molecular basis of the triple negative breast cancer

    OpenAIRE

    Ayse Feyda Nursal

    2015-01-01

    Breast cancer is the most common type of cancer in women and more than 1 million breast cancer cases are diagnosed each year all over the world. Breast cancer is a complex and heterogeneous disease in terms of its molecular structure, mutation type, metastase properties, clinical course and therapeutic response. Breast cancer is divided into subtypes based on expression properties of molecular markers as estrogen receptor, progestron receptor, human epidermal growth factor receptor 2. Triple-...

  20. Breast cancer risk factors

    OpenAIRE

    Marzena Kamińska; Tomasz Ciszewski; Karolina Łopacka-Szatan; Paweł Miotła; Elżbieta Starosławska

    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 neopla...

  1. Diet and breast cancer

    OpenAIRE

    Isabelle Romieu

    2011-01-01

    Both diet and nutrition have been studied in relationship with breast cancer risk, as the great variation among different countries in breast cancer incidence could possibly be explained through the inflammatory and immune response, as well as antioxidant intake, among others.To date, no clear association with diet beyond overweight and weight gain has been found, except for alcohol consumption. Nonetheless, the small number of studies done in middle to low income countries where variability ...

  2. Women and breast cancer.

    OpenAIRE

    Lippman, M E

    1987-01-01

    One in every 12 women will develop breast cancer; the incidence increases with age, dietary fat intake, caloric intake, height, and weight. The 10-year survival rate of breast cancer patients who refuse therapy is virtually zero. Segmental mastectomy plus radiation and lumpectomy, combined with systemic (adjuvant)chemotherapy, are alternatives under investigation at the National Institutes of Health that may increase the survival rate by decreasing metastatic complications.

  3. Targeting Breast Cancer Metastasis

    OpenAIRE

    Xin Jin; Ping Mu

    2015-01-01

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

  4. AZD8931, an equipotent, reversible inhibitor of signaling by epidermal growth factor receptor (EGFR), HER2, and HER3: preclinical activity in HER2 non-amplified inflammatory breast cancer models

    OpenAIRE

    Mu, Zhaomei; Klinowska, Teresa; Dong, Xiaoshen; Foster, Emily; Womack, Chris; Fernandez, Sandra V.; Cristofanilli, Massimo

    2014-01-01

    Introduction Epidermal growth factor receptor (EGFR) overexpression has been associated with prognostic and predictive value in inflammatory breast cancer (IBC). Epidermal growth factor receptor 2 (HER2) overexpression is observed at a higher rate in IBC compared with noninflammatory breast cancer. Current clinically available anti-HER2 therapies are effective only in patients with HER2 amplified breast cancer, including IBC. AZD8931 is a novel small-molecule equipotent inhibitor of EGFR, HER...

  5. Mead acid inhibits the growth of KPL-1 human breast cancer cells in vitro and in vivo.

    Science.gov (United States)

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

    2014-10-01

    The effects of mead acid (MA; 5,8,11-eicosatrienoic acid) on the suppression of breast cancer cell growth and metastasis were examined in vitro and in vivo by using the KPL-1 human breast cancer cell line. MA suppressed KPL-1 cell growth in culture with an IC50 value of 214.2 µM (65.7 µg/ml) for 72 h, and MA significantly suppressed transplanted KPL-1 tumor growth (tumor volume and tumor weight: 872±103 mm3 and 1,000±116 mg vs. 376±66 mm3 and 517±84 mg) and regional (axillary) lymph node metastasis (67%, 10/15 vs. 10%, 1/10) in female athymic mice fed an MA-rich diet for 8 weeks. Tumor suppression was due to the suppression of cell proliferation. In ELISA, although vascular endothelial growth factor (VEGF) levels were unchanged, VEGF receptor (VEGFR)1 and VEGFR2 levels were significantly decreased after treatment with a 214.2-µM dose of MA for 72 h; E-cadherin levels were unchanged. As VEGF, VEGFR1 and VEGFR2 expression was co-localized in KPL-1 cells, the mechanism leading to cell growth suppression was VEGF signaling directly to KPL-1 cells by an autocrine process. In contrast, MA did not influence angiogenesis. The mechanisms of action were through VEGF signaling directly to cancer cells. PMID:25109488

  6. Inhibition of insulin-like growth factor-1 receptor signaling enhances growth-inhibitory and proapoptotic effects of gefitinib (Iressa) in human breast cancer cells

    International Nuclear Information System (INIS)

    Gefitinib (Iressa, ZD 1839, AstraZeneca) blocks the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) and inhibits proliferation of several human cancer cell types including breast cancer. Phase II clinical trials with gefitinib monotherapy showed an objective response of 9 to 19% in non-small-cell lung cancer patients and less than 10% for breast cancer, and phase III results have indicated no benefit of gefitinib in combination with chemotherapy over chemotherapy alone. In order to improve the antineoplastic activity of gefitinib, we investigated the effects of blocking the signalling of the insulin-like growth factor 1 receptor (IGF-1R), a tyrosine kinase with a crucial role in malignancy that is coexpressed with EGFR in most human primary breast carcinomas. AG1024 (an inhibitor of IGF-1R) was used with gefitinib for treatment of MDA468, MDA231, SK-BR-3, and MCF-7 breast cancer lines, which express similar levels of IGF-1R but varying levels of EGFR. Proliferation assays, apoptosis induction studies, and Western blot analyses were conducted with cells treated with AG1024 and gefitinib as single agents and in combination. Gefitinib and AG1024 reduced proliferation in all lines when used as single agents, and when used in combination revealed an additive-to-synergistic effect on cell growth inhibition. Flow cytometry measurements of cells stained with annexin V-propidium iodide and cells stained for caspase-3 activation indicated that adding an IGF-1R-targeting strategy to gefitinib results in higher levels of apoptosis than are achieved with gefitinib alone. Gefitinib either reduced or completely inhibited p42/p44 Erk kinase phosphorylation, depending on the cell line, while Akt phosphorylation was reduced by a combination of the two agents. Overexpression of IGF-1R in SK-BR-3 cells was sufficient to cause a marked enhancement in gefitinib resistance. These results indicate that IGF-1R signaling reduces the antiproliferative effects of

  7. High TDP43 expression is required for TRIM16-induced inhibition of cancer cell growth and correlated with good prognosis of neuroblastoma and breast cancer patients.

    Science.gov (United States)

    Kim, Patrick Y; Tan, Owen; Liu, Bing; Trahair, Toby; Liu, Tao; Haber, Michelle; Norris, Murray D; Marshall, Glenn M; Cheung, Belamy B

    2016-05-01

    Tripartite Motif-containing protein 16 (TRIM16) is a member of a large family of tripartite motif (TRIM) proteins, that has been implicated in the pathogenesis of multiple cancers. However, the mechanism by which TRIM16 acts as a tumour suppressor is currently unknown. We used the versatile yeast two-hybrid assay on a cDNA library from human testes, which has relative high TRIM16 expression, to identify potential TRIM16-binding proteins. We identified transactive response DNA-binding protein 43 (TDP43) as a novel TRIM16 binding protein. Co-immunoprecipitation assay demonstrated that TDP43 bound TRIM16 in neuroblastoma and breast cancer cells. Enforced over-expression of TRIM16 increased the protein half-life of TDP43, through the inhibition of the proteosomal degradation pathway. High levels of TRIM16 and TDP43 are associated with good prognosis in both human neuroblastoma and breast cancer tissues. Importantly, we found TDP43 expression was required for TRIM16-induced inhibition of neuroblastoma and breast cancer cell growth and the repressive effect of TRIM16 on cell cycle regulatory proteins, E2F1 and pRb. Taken together, our data suggest that TRIM16 and TDP43 are both good prognosis indicators; also we showed that TRIM16 inhibits cancer cell viability by a novel mechanism involving interaction and stabilisation of TDP43 with consequent effects on E2F1 and pRb proteins. PMID:26902425

  8. Insulin-like growth factor-1 signaling regulates miRNA expression in MCF-7 breast cancer cell line.

    Directory of Open Access Journals (Sweden)

    Elizabeth C Martin

    Full Text Available In breast carcinomas, increased levels of insulin-like growth factor 1 (IGF-1 can act as a mitogen to augment tumorigenesis through the regulation of MAPK and AKT signaling pathways. Signaling through these two pathways allows IGF-1 to employ mechanisms that favor proliferation and cellular survival. Here we demonstrate a subset of previously described tumor suppressor and oncogenic microRNAs (miRNAs that are under the direct regulation of IGF-1 signaling. Additionally, we show that the selective inhibition of either the MAPK or AKT pathways prior to IGF-1 stimulation prevents the expression of previously described tumor suppressor miRNAs that are family and cluster specific. Here we have defined, for the first time, specific miRNAs under the direct regulation of IGF-1 signaling in the estrogen receptor positive MCF-7 breast cancer cell line and demonstrate kinase signaling as a modulator of expression for a small subset of microRNAs. Taken together, these data give new insights into mechanisms governing IGF-1 signaling in breast cancer.

  9. Enrichment of breast cancer stem-like cells by growth on electrospun polycaprolactone-chitosan nanofiber scaffolds

    OpenAIRE

    Sims-Mourtada J; Niamat RA; Samuel S; Eskridge C; Kmiec EB

    2014-01-01

    Jennifer Sims-Mourtada,1 Rohina A Niamat,2 Shani Samuel,2 Chris Eskridge,2 Eric B Kmiec1,2 1Center for Translational Cancer Research, Helen F Graham Cancer Center and Research Institute, Christiana Care Health Services, Inc, Newark, 2Department of Chemistry, Delaware State University, Dover, DE, USA Abstract: A small population of highly tumorigenic breast cancer cells has recently been identified. These cells, known as breast-cancer stem-like cells (BCSC), express markers similar to mammary...

  10. SRC drives growth of antiestrogen resistant breast cancer cell lines and is a marker for reduced benefit of tamoxifen treatment

    DEFF Research Database (Denmark)

    Larsen, Sarah L; Laenkholm, Anne-Vibeke; Duun-Henriksen, Anne Katrine;

    2015-01-01

    The underlying mechanisms leading to antiestrogen resistance in estrogen-receptor α (ER)-positive breast cancer is still poorly understood. The aim of this study was therefore to identify biomarkers and novel treatments for antiestrogen resistant breast cancer. We performed a kinase inhibitor scr...

  11. Role of ornithine decarboxylase in regulation of estrogen receptor alpha expression and growth in human breast cancer cells.

    Science.gov (United States)

    Zhu, Qingsong; Jin, Lihua; Casero, Robert A; Davidson, Nancy E; Huang, Yi

    2012-11-01

    Our previous studies demonstrated that specific polyamine analogues, oligoamines, down-regulated the activity of a key polyamine biosynthesis enzyme, ornithine decarboxylase (ODC), and suppressed expression of estrogen receptor alpha (ERα) in human breast cancer cells. However, the mechanism underlying the potential regulation of ERα expression by polyamine metabolism has not been explored. Here, we demonstrated that RNAi-mediated knockdown of ODC (ODC KD) down-regulated the polyamine pool, and hindered growth in ERα-positive MCF7 and T47D and ERα-negative MDA-MB-231 breast cancer cells. ODC KD significantly induced the expression and activity of the key polyamine catabolism enzymes, spermine oxidase (SMO) and spermidine/spermine N (1)-acetyltransferase (SSAT). However, ODC KD-induced growth inhibition could not be reversed by exogenous spermidine or overexpression of antizyme inhibitor (AZI), suggesting that regulation of ODC on cell proliferation may involve the signaling pathways independent of polyamine metabolism. In MCF7 and T47D cells, ODC KD, but not DFMO treatment, diminished the mRNA and protein expression of ERα. Overexpression of antizyme (AZ), an ODC inhibitory protein, suppressed ERα expression, suggesting that ODC plays an important role in regulation of ERα expression. Decrease of ERα expression by ODC siRNA altered the mRNA expression of a subset of ERα response genes. Our previous analysis showed that oligoamines disrupt the binding of Sp1 family members to an ERα minimal promoter element containing GC/CA-rich boxes. By using DNA affinity precipitation and mass spectrometry analysis, we identified ZBTB7A, MeCP2, PARP-1, AP2, and MAZ as co-factors of Sp1 family members that are associated with the ERα minimal promoter element. Taken together, these data provide insight into a novel antiestrogenic mechanism for polyamine biosynthesis enzymes in breast cancer. PMID:22976807

  12. Herbal Extract SH003 Suppresses Tumor Growth and Metastasis of MDA-MB-231 Breast Cancer Cells by Inhibiting STAT3-IL-6 Signaling

    Directory of Open Access Journals (Sweden)

    Youn Kyung Choi

    2014-01-01

    Full Text Available Cancer inflammation promotes cancer progression, resulting in a high risk of cancer. Here, we demonstrate that our new herbal extract, SH003, suppresses both tumor growth and metastasis of MDA-MB-231 breast cancer cells via inhibiting STAT3-IL-6 signaling path. Our new herbal formula, SH003, mixed extract from Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii Maximowicz, suppressed MDA-MB-231 tumor growth and lung metastasis in vivo and reduced the viability and metastatic abilities of MDA-MB-231 cells in vitro. Furthermore, SH003 inhibited STAT3 activation, which resulted in a reduction of IL-6 production. Therefore, we conclude that SH003 suppresses highly metastatic breast cancer growth and metastasis by inhibiting STAT3-IL-6 signaling path.

  13. Essiac? and Flor-Essence? herbal tonics stimulate the in vitro growth of human breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Kulp, K S; Montgomery, J L; McLimans, B; Latham, E R; Shattuck, D L; Klotz, D M; Bennett, L M

    2005-10-07

    People diagnosed with cancer often self-administer complementary and alternative medicines (CAMs) to supplement their conventional treatments, improve health, or prevent recurrence. Flor-Essence{reg_sign} and Essiac{reg_sign} Herbal Tonics are commercially available complex mixtures of herbal extracts sold as dietary supplements and used by cancer patients based on anecdotal evidence that they can treat or prevent disease. In this study, we evaluated Flor-Essence{reg_sign} and Essiac{reg_sign} for their effects on the growth of human tumor cells in culture. The effect of Flor-Essence{reg_sign} and Essiac{reg_sign} herbal tonics on cell proliferation was tested in MCF-7, MDA-MB-436, MDA-MB-231, and T47D cancer cells isolated from human breast tumors. Estrogen receptor (ER) dependent activation of a luciferase reporter construct was tested in MCF-7 cells. Specific binding to the ER was tested using an ICI 182,780 competition assay. Flor-Essence{reg_sign} and Essiac{reg_sign} herbal tonics at 1%, 2%, 4% and 8% stimulated cell proliferation relative to untreated controls and activated ER dependent luciferase activity in MCF-7 cells. A 10{sup -7} M concentration of ICI 870,780 inhibited the induction of ER dependent luciferase activity by Flor-Essence{reg_sign} and Essiac{reg_sign}, but did not affect cell proliferation. Flor-Essence{reg_sign} and Essiac{reg_sign} Herbal Tonics can stimulate the growth of human breast cancer cells through ER mediated as well as ER independent mechanisms of action. Cancer patients and health care providers can use this information to make informed decisions about the use of these CAMs.

  14. Viruses and Breast Cancer

    International Nuclear Information System (INIS)

    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

  15. Viruses and Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lawson, James S., E-mail: james.lawson@unsw.edu.au; Heng, Benjamin [School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney (Australia)

    2010-04-30

    Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify viruses which may have a role in breast cancer. Despite these efforts, the establishment of conclusive evidence for such a role has been elusive. However, the development of extremely sophisticated new experimental techniques has allowed the recent development of evidence that human papilloma virus, Epstein-Barr virus, mouse mammary tumor virus and bovine leukemia virus may each have a role in the causation of human breast cancers. This is potentially good news as effective vaccines are already available to prevent infections from carcinogenic strains of human papilloma virus, which causes cancer of the uterine cervix.

  16. Breast cancer statistics and markers

    OpenAIRE

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

    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...

  17. Loss of growth inhibitory effects of retinoic acid in human breast cancer cells following long-term exposure to retinoic acid

    OpenAIRE

    Stephen, R; Darbre, P D

    2000-01-01

    Although retinoids are known to be inhibitory to breast cancer cell growth, a key remaining question is whether they would remain effective if administered long-term. We describe here the long-term effects of all-trans retinoic acid on two oestrogen-dependent human breast cancer cell lines MCF7 and ZR-75-1. Although both cell lines were growth inhibited by retinoic acid in the short-term in either the absence or the presence of oestradiol, prolonged culture with 1 μM all-trans retinoic acid r...

  18. Chemotherapy cytotoxicity of human MCF-7 and MDA-MB 231 breast cancer cells is altered by osteoblast-derived growth factors.

    OpenAIRE

    Koutsilieris, M; Reyes-Moreno, C.; Choki, I.; Sourla, A.; Doillon, C.; Pavlidis, N.

    1999-01-01

    One-third of women with breast cancer will develop bone metastases and eventually die from disease progression at these sites. Therefore, we analyzed the ability of human MG-63 osteoblast-like cells (MG-63 cells), MG-63 conditioned media (MG-63 CM), insulin-like growth factor I (IGF-I), and transforming growth factor beta 1 (TGF-beta1) to alter the effects of adriamycin on cell cycle and apoptosis of estrogen receptor negative (ER-) MDA-MB-231 and positive (ER+) MCF-7 breast cancer cells, usi...

  19. The HER2 amplicon includes several genes required for the growth and survival of HER2 positive breast cancer cells — A data description

    Directory of Open Access Journals (Sweden)

    Vesa Hongisto

    2014-12-01

    Full Text Available A large number of breast cancers are characterized by amplification and overexpression of the chromosome segment surrounding the HER2 (ERBB2 oncogene. As the HER2 amplicon at 17q12 contains multiple genes, we have systematically explored the role of the HER2 co-amplified genes in breast cancer cell growth and their relation to trastuzumab resistance. We integrated array comparative genomic hybridization (aCGH data of the HER2 amplicon from 71 HER2 positive breast tumors and 10 cell lines with systematic functional RNA interference analysis of 23 core amplicon genes with several phenotypic endpoints in a panel of trastuzumab responding and non-responding HER2 positive breast cancer cells. In this Data in Brief we give a detailed description of the experimental procedures and the data analysis methods used in the study (1.

  20. Breast Cancer Detection

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    2015-08-27

    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

  2. Evaluation of Vascular Endothelial Growth Factor as a Prognostic Marker for Local Relapse in Early-Stage Breast Cancer Patients Treated With Breast-Conserving Therapy

    International Nuclear Information System (INIS)

    Purpose: Vascular endothelial growth factor (VEGF) is an important protein involved in the process of angiogenesis that has been found to correlate with relapse-free and overall survival in breast cancer, predominantly in locally advanced and metastatic disease. A paucity of data is available on the prognostic implications of VEGF in early-stage breast cancer; specifically, its prognostic value for local relapse after breast-conserving therapy (BCT) is largely unknown. The purpose of our study was to assess VEGF expression in a cohort of early-stage breast cancer patients treated with BCT and to correlate the clinical and pathologic features and outcomes with overexpression of VEGF. Methods and Materials: After obtaining institutional review board approval, the paraffin specimens of 368 patients with early-stage breast cancer treated with BCT between 1975 and 2005 were constructed into tissue microarrays with twofold redundancy. The tissue microarrays were stained for VEGF and read by a trained pathologist, who was unaware of the clinical details, as positive or negative according the standard guidelines. The clinical and pathologic data, long-term outcomes, and results of VEGF staining were analyzed. Results: The median follow-up for the entire cohort was 6.5 years. VEGF expression was positive in 56 (15%) of the 368 patients. Although VEGF expression did not correlate with age at diagnosis, tumor size, nodal status, histologic type, family history, estrogen receptor/progesterone receptor status, or HER-2 status, a trend was seen toward increased VEGF expression in the black cohort (26% black vs. 13% white, p = .068). Within the margin-negative cohort, VEGF did not predict for local relapse-free survival (RFS) (96% vs. 95%), nodal RFS (100% vs. 100%), distant metastasis-free survival (91% vs. 92%), overall survival (92% vs. 97%), respectively (all p >.05). Subset analysis revealed that VEGF was highly predictive of local RFS in node-positive, margin

  3. Suppressive effects of a proton beam on tumor growth and lung metastasis through the inhibition of metastatic gene expression in 4T1 orthotopic breast cancer model.

    Science.gov (United States)

    Kwon, Yun-Suk; Lee, Kyu-Shik; Chun, So-Young; Jang, Tae Jung; Nam, Kyung-Soo

    2016-07-01

    A proton beam is a next generation tool to treat intractable cancer. Although the therapeutic effects of a proton beam are well known, the effect on tumor metastasis is not fully described. Here, we investigated the effects of a proton beam on metastasis in highly invasive 4T1 murine breast cancer cells and their orthotopic breast cancer model. Cells were irradiated with 2, 4, 8 or 16 Gy proton beam, and changes in cell proliferation, survival, and migration were observed by MTT, colony forming and wound healing assays. 4T1 breast cancer cell-implanted BALB/c mice were established and the animals were randomly divided into 4 groups when tumor size reached 200 mm3. Breast tumors were selectively irradiated with 10, 20 or 30 Gy proton beam. Breast tumor sizes were measured twice a week, and breast tumor and lung tissues were pathologically observed. Metastasis-regulating gene expression was assessed with quantitative RT-PCR. A proton beam dose-dependently decreased cell proliferation, survival and migration in 4T1 murine breast cancer cells. Also, growth of breast tumors in the 4T1 orthotopic breast cancer model was significantly suppressed by proton beam irradiation without significant change of body weight. Furthermore, fewer tumor nodules metastasized from breast tumor into lung in mice irradiated with 30 Gy proton beam, but not with 10 and 20 Gy, than in control. We observed correspondingly lower expression levels of urokinase plasminogen activator (uPA), uPA receptor, cyclooxygenase (COX)-2, and vascular endothelial growth factor (VEGF), which are important factors in cancer metastasis, in breast tumor irradiated with 30 Gy proton beam. Proton beam irradiation did not affect expressions of matrix metalloproteinase (MMP)-9 and MMP-2. Taken together, the data suggest that, although proton beam therapy is an effective tool for breast cancer treatment, a suitable dose is necessary to prevent metastasis-linked relapse and poor prognosis. PMID:27176787

  4. Breast cancer chemoprevention

    Directory of Open Access Journals (Sweden)

    Ivana Sestak

    2011-12-01

    Full Text Available Trials with tamoxifen have clearly shown that the risk of developing oestrogen receptor positive breast cancer can be reduced by at least 50% with prophylactic agents. The current challenge is to find new agents which achieve this or better efficacy, but with fewer side effects. Recent results indicate that the SERM raloxifene has similar efficacy to tamoxifen, but leads to fewer endometrial cancers, gynecological symptoms, and thromboembolic events. Results for contralateral tumors in adjuvant trials suggest that aromatase inhibitors may be able to prevent up to 70%–80% of ER-positive breast cancers, and this is currently being investigated in two large prevention trials, one using anastrozole (IBIS-II and the other exemestane (MAP.3. New agents are needed for receptor negative breast cancer and several possibilities are currently under investigation.

  5. Life After Breast Cancer Treatment

    Science.gov (United States)

    FACTS FOR LIFE Life After Breast Cancer Treatment Once breast cancer treatment ends, you may face a new set of issues and concerns. ... fear. If fear starts to disrupt your daily life, talk to your doctor. Getting the support and ...

  6. Vitamin D and Breast Cancer

    OpenAIRE

    Shao, Theresa; Klein, Paula; Grossbard, Michael L.

    2012-01-01

    Vitamin D metabolism and its mechanism of action, the current evidence on the relationship between vitamin D and breast cancer, and the optimal dosing of vitamin D for breast cancer prevention are summarized.

  7. Preventing Breast Cancer: Making Progress

    Science.gov (United States)

    ... Navigation Bar Home Current Issue Past Issues Preventing Breast Cancer: Making Progress Past Issues / Fall 2006 Table of ... 000 women will have been diagnosed with invasive breast cancer, and nearly 41,000 women will die from ...

  8. Estrogen receptor prevents p53-dependent apoptosis in breast cancer

    OpenAIRE

    Bailey, Shannon T.; Shin, Hyunjin; Westerling, Thomas; Liu, Xiaole Shirley; Brown, Myles

    2012-01-01

    More than two-thirds of breast cancers express the estrogen receptor (ER) and depend on estrogen for growth and survival. Therapies targeting ER function, including aromatase inhibitors that block the production of estrogens and ER antagonists that alter ER transcriptional activity, play a central role in the treatment of ER+ breast cancers of all stages. In contrast to ER− breast cancers, which frequently harbor mutations in the p53 tumor suppressor, ER+ breast cancers are predominantly wild...

  9. Co-inhibition of epidermal growth factor receptor and insulin-like growth factor receptor 1 enhances radiosensitivity in human breast cancer cells

    International Nuclear Information System (INIS)

    Over-expression of epidermal growth factor receptor (EGFR) or insulin-like growth factor-1 receptor (IGF-1R) have been shown to closely correlate with radioresistance of breast cancer cells. This study aimed to investigate the impact of co-inhibition of EGFR and IGF-1R on the radiosensitivity of two breast cancer cells with different profiles of EGFR and IGF-1R expression. The MCF-7 (EGFR +/−, IGF-1R +++) and MDA-MB-468 (EGFR +++, IGF-1R +++) breast cancer cell lines were used. Radiosensitizing effects were determined by colony formation assay. Apoptosis and cell cycle distribution were measured by flow cytometry. Phospho-Akt and phospho-Erk1/2 were quantified by western blot. In vivo studies were conducted using MDA-MB-468 cells xenografted in nu/nu mice. In MDA-MB-468 cells, the inhibition of IGF-1R upregulated the p-EGFR expression. Either EGFR (AG1478) or IGF-1R inhibitor (AG1024) radiosensitized MDA-MB-468 cells. In MCF-7 cells, radiosensitivity was enhanced by AG1024, but not by AG1478. Synergistical radiosensitizing effect was observed by co-inhibition of EGFR and IGF-1R only in MDA-MB-468 cells with a DMF10% of 1.90. The co-inhibition plus irradiation significantly induced more apoptosis and arrested the cells at G0/G1 phase in MDA-MB-468 cells. Only co-inhibition of EGFR and IGF-1R synergistically diminished the expression of p-Akt and p-Erk1/2 in MDA-MB-468 cells. In vivo studies further verified the radiosensitizing effects by co-inhibition of both pathways in a MDA-MB-468 xenograft model. Our data suggested that co-inhibition of EGFR and IGF-1R synergistically radiosensitized breast cancer cells with both EGFR and IGF-1R high expression. The approach may have an important therapeutic implication in the treatment of breast cancer patients with high expression of EGFR and IGF-1R

  10. FGF receptor genes and breast cancer susceptibility

    DEFF Research Database (Denmark)

    Agarwal, D; Pineda, S; Michailidou, K;

    2014-01-01

    Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying......, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression.Results:Little evidence of association with breast cancer risk...... that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2....

  11. A truncated phosphorylated p130Cas substrate domain is sufficient to drive breast cancer growth and metastasis formation in vivo.

    Science.gov (United States)

    Kumbrink, Joerg; de la Cueva, Ana; Soni, Shefali; Sailer, Nadja; Kirsch, Kathrin H

    2016-08-01

    Elevated p130Cas (Crk-associated substrate) levels are found in aggressive breast tumors and are associated with poor prognosis and resistance to standard therapeutics in patients. p130Cas signals majorly through its phosphorylated substrate domain (SD) that contains 15 tyrosine motifs (YxxP) which recruit effector molecules. Tyrosine phosphorylation of p130Cas is important for mediating migration, invasion, tumor promotion, and metastasis. We previously developed a Src*/SD fusion molecule approach, where the SD is constitutively phosphorylated. In a polyoma middle T-antigen (PyMT)/Src*/SD double-transgenic mouse model, Src*/SD accelerates PyMT-induced tumor growth and promotes a more aggressive phenotype. To test whether Src*/SD also drives metastasis and which of the YxxP motifs are involved in this process, full-length and truncated SD molecules fused to Src* were expressed in breast cancer cells. The functionality of the Src*/SD fragments was analyzed in vitro, and the active proteins were tested in vivo in an orthotopic mouse model. Breast cancer cells expressing the full-length SD and the functional smaller SD fragment (spanning SD motifs 6-10) were injected into the mammary fat pads of mice. The tumor progression was monitored by bioluminescence imaging and caliper measurements. Compared with control animals, the complete SD promoted primary tumor growth and an earlier onset of metastases. Importantly, both the complete and truncated SD significantly increased the occurrence of metastases to multiple organs. These studies provide strong evidence that the phosphorylated p130Cas SD motifs 6-10 (Y236, Y249, Y267, Y287, and Y306) are important for driving mammary carcinoma progression. PMID:26867768

  12. Deep Proteomics of Breast Cancer Cells Reveals that Metformin Rewires Signaling Networks Away from a Pro-growth State.

    Science.gov (United States)

    Sacco, Francesca; Silvestri, Alessandra; Posca, Daniela; Pirrò, Stefano; Gherardini, Pier Federico; Castagnoli, Luisa; Mann, Matthias; Cesareni, Gianni

    2016-03-23

    Metformin is the most frequently prescribed drug for type 2 diabetes. In addition to its hypoglycemic effects, metformin also lowers cancer incidence. This anti-cancer activity is incompletely understood. Here, we profiled the metformin-dependent changes in the proteome and phosphoproteome of breast cancer cells using high-resolution mass spectrometry. In total, we quantified changes of 7,875 proteins and 15,813 phosphosites after metformin changes. To interpret these datasets, we developed a generally applicable strategy that overlays metformin-dependent changes in the proteome and phosphoproteome onto a literature-derived network. This approach suggested that metformin treatment makes cancer cells more sensitive to apoptotic stimuli and less sensitive to pro-growth stimuli. These hypotheses were tested in vivo; as a proof-of-principle, we demonstrated that metformin inhibits the p70S6K-rpS6 axis in a PP2A-phosphatase dependent manner. In conclusion, analysis of deep proteomics reveals both detailed and global mechanisms that contribute to the anti-cancer activity of metformin. PMID:27135362

  13. Characterization of fibroblast growth factor receptor 2 overexpression in the human breast cancer cell line SUM-52PE

    International Nuclear Information System (INIS)

    The fibroblast growth factor receptor (FGFR)2 gene has been shown to be amplified in 5-10% of breast cancer patients. A breast cancer cell line developed in our laboratory, SUM-52PE, was shown to have a 12-fold amplification of the FGFR2 gene, and FGFR2 message was found to be overexpressed 40-fold in SUM-52PE cells as compared with normal human mammary epithelial (HME) cells. Both human breast cancer (HBC) cell lines and HME cells expressed two FGFR2 isoforms, whereas SUM-52PE cells overexpressed those two isoforms, as well as several unique FGFR2 polypeptides. SUM-52PE cells expressed exclusively FGFR2-IIIb isoforms, which are high-affinity receptors for fibroblast growth factor (FGF)-1 and FGF-7. Differences were identified in the expression of the extracellular Ig-like domains, acid box and carboxyl termini, and several variants not previously reported were isolated from these cells. The FGFR family of receptor tyrosine kinases includes four members, all of which are highly alternatively spliced and glycosylated. For FGFR2, alternative splicing of the second half of the third Ig-like domain, involving exons IIIb and IIIc, is a mutually exclusive choice that affects ligand binding specificity and affinity [1,2,3]. It appears that the second half of the third Ig-like domain can dictate high affinity for FGF-2 or keratinocyte growth factor (KGF), whereas affinity for FGF-1 appears to remain the same [3]. Alternative splicing of the carboxyl terminus has been shown to involve at least two different exons that can produce at least three different variants. The C1-type and C2-type carboxyl termini are encoded by the same exon, and have two different splice acceptor sites, whereas the C3-type carboxyl terminus is encoded by a separate exon [4]. The biologic significance of the C1 carboxyl terminus, as compared with the shorter C3 variant found primarily in tumorigenic samples, has been studied in NIH3T3 transfection assays, in which C3 variants were able to produce

  14. Efficient inhibition of murine breast cancer growth and metastasis by gene transferred mouse survivin Thr34→Ala mutant

    Directory of Open Access Journals (Sweden)

    Chen li-Juan

    2008-09-01

    Full Text Available Abstract Background Metastasis in breast cancer is a vital concern in treatment because most women with primary breast cancer have micrometastases to distant sites at diagnosis. As a member of the inhibitor of apoptosis protein (IAP family, survivin has been proposed as an attractive target for new anticancer interventions. In this study, we investigated the role of the plasmid encoding the phosphorylation-defective mouse survivin threonine 34→alanine mutant (Msurvivin T34A plasmid in suppressing both murine primary breast carcinomas and pulmonary metastases. Methods In vitro study, induction of apoptosis by Msurvivin T34A plasmid complexed with cationic liposome (DOTAP/Chol was examined by PI staining fluorescence microscopy and flow cytometric analysis. The anti-tumor and anti-metastases activity of Msurvivin T34A plasmid complexed with cationic liposome (DOTAP/Chol was evaluated in female BALB/c mice bearing 4T1 s.c. tumors. Mice were treated twice weekly with i.v. administration of Msurvivin T34A plasmid complexed with cationic liposome (DOTAP/Chol, PORF-9 null plasmid complexed with cationic liposome (DOTAP/Chol, 0.9% NaCl solution for 4 weeks. Tumor volume was observed. After sacrificed, tumor net weight was measured and Lung metastatic nodules of each group were counted. Assessment of apoptotic cells by TUNEL assay was conducted in tumor tissue. Microvessel density within tumor tissue was determined by CD31 immunohistochemistry. Alginate-encapsulated tumor cells test was conducted to evaluate the effect on angiogenesis. By experiment of cytotoxicity T lymphocytes, we test whether Msurvivin T34A plasmid complexed with cationic liposome (DOTAP/Chol can induce specific cell immune response. Results Administration of Msurvivin T34A plasmid complexed with cationic liposome (DOTAP/Chol resulted in significant inhibition in the growth and metastases of 4T1 tumor model. These anti-tumor and anti-metastases responses were associated with

  15. Decreased expression of the mannose 6- phosphate/insulin-like growth factor-II receptor promotes growth of human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Landman Natalie

    2002-07-01

    Full Text Available Abstract Background Loss or mutation of the mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGF2R has been found in breast cancer. However, whether or not decreased levels of functional M6P/IGF2R directly contribute to the process of carcinogenesis needs to be further verified by functional studies. Methods In this study, using viral and ribozyme strategies we reduced the expression of M6P/IGF2R in human breast cancer cells and then examined the effect on growth and apoptosis of these cells. Results Our results showed that infection of MCF-7 cells with the adenovirus carrying a ribozyme targeted against the M6P/IGF2R mRNA dramatically reduced the level of transcripts and the functional activity of M6P/IGF2R in these cells. Accordingly, cells treated with the ribozyme exhibited a higher growth rate and a lower apoptotic index than control cells (infected with a control vector. Furthermore, decreased expression of M6P/IGF2R enhanced IGF-II-induced proliferation and reduced cell susceptibility to TNF-induced apoptosis. Conclusions These results suggest that M6P/IGF2R functions as a growth suppressor and its loss or mutation may contribute to development and progression of cancer. This study also demonstrates that adenoviral delivery of the ribozyme provides a useful tool for investigating the role of M6P/IGF2R in regulation of cell growth.

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

    Science.gov (United States)

    2016-03-17

    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. Andrographolide inhibits hypoxia-inducible factor-1 through phosphatidylinositol 3-kinase/AKT pathway and suppresses breast cancer growth

    Directory of Open Access Journals (Sweden)

    Li J

    2015-02-01

    Full Text Available Jie Li,1 Chao Zhang,1 Hongchuan Jiang,1 Jiao Cheng21Department of General Surgery, 2Department of Gynaecology and Obstetrics, Beijing Chao-Yang Hospital, Beijing, People’s Republic of ChinaAbstract: Hypoxia-inducible factor-1 (HIF-1 is a master regulator of the transcriptional response to hypoxia. HIF-1α is one of the most compelling anticancer targets. Andrographolide (Andro was newly identified to inhibit HIF-1 in T47D cells (a half maximal effective concentration [EC50] of 1.03×10-7 mol/L, by a dual-luciferase reporter assay. It suppressed HIF-1α protein and gene accumulation, which was dependent on the inhibition of upstream phosphatidylinositol 3-kinase (PI3K/AKT pathway. It also abrogated the expression of HIF-1 target vascular endothelial growth factor (VEGF gene and protein. Further, Andro inhibited T47D and MDA-MB-231 cell proliferation and colony formation. In addition, it exhibited significant in vivo efficacy and antitumor potential against the MDA-MB-231 xenograft in nude mice. In conclusion, these results highlighted the potential effects of Andro, which inhibits HIF-1, and hence may be developed as an antitumor agent for breast cancer therapy in future.Keywords: Andrographolide (Andro, HIF-1α, inhibit, breast cancer, hypoxia, PI3k/AKT/mTOR pathway

  18. Breast cancer screening

    OpenAIRE

    Skrabanek, P

    1988-01-01

    Consensus is still lacking on guidelines for breast-cancer screening with mammography: who should be screened, how frequently at what age, to what benefits and at what risks. American, Dutch, Swedish and Italian studies spanning the 1960s to the 1980s reveal a benefit from screening (reduced mortality from breast cancer) that occurs unambiguously only in women 50 years of age and over. Physicians who choose to screen mammographically their over-49-year-old female patients must do so with the ...

  19. Inheritance of proliferative breast disease in breast cancer kindreds

    International Nuclear Information System (INIS)

    Previous studies have emphasized that genetic susceptibility to breast cancer is rare and is expressed primarily as premenopausal breast cancer, bilateral breast cancer, or both. Proliferative breast disease (PBD) is a significant risk factor for the development of breast cancer and appears to be a precursor lesion. PBD and breast cancer were studied in 103 women from 20 kindreds that were selected for the presence of two first degree relatives with breast cancer and in 31 control women. Physical examination, screening mammography, and four-quadrant fine-needle breast aspirates were performed. Cytologic analysis of breast aspirates revealed PBD in 35% of clinically normal female first degree relatives of breast cancer cases and in 13% of controls. Genetic analysis suggests that genetic susceptibility causes both PBD and breast cancer in these kindreds. This study supports the hypothesis that this susceptibility is responsible for a considerable portion of breast cancer, including unilateral and postmenopausal breast cancer

  20. Berberine in combination with cisplatin suppresses breast cancer cell growth through induction of DNA breaks and caspase-3-dependent apoptosis.

    Science.gov (United States)

    Zhao, Yuwan; Jing, Zuolei; Li, Yan; Mao, Weifeng

    2016-07-01

    Berberine (BBR) is an isoquinoline alkaloid extracted from medicinal plants such as Hydrastis canadensis, Berberis aristata and Coptis chinensis. BBR displays a number of beneficial roles in the treatment of various types of cancers, yet the precise mechanisms of its action remain unclear. Cisplatin is an effective cancer chemotherapeutic agent and functions by generating DNA damage, promoting DNA damage-induced cell cycle arrest and apoptosis; however, its efficacy is challenged by the resistance of tumor cells in clinical application. The aim of the present study was to investigate the effects of BBR in combination with cisplatin on human breast cancer cells. MTT assay showed that BBR inhibited breast cancer MCF-7 cell growth with a 50% inhibitory concentration (IC50) value of 52.178±1.593 µM and the IC50 value of cisplatin was 49.541±1.618 µM, while in combination with 26 µM BBR, the IC50 value of cisplatin was 5.759±0.76 µM. BBR sensitized the MCF-7 cells to cisplatin in a time- and dose-dependent manner. After treatment of BBR and cisplatin, the cellular pro-apoptotic capase-3 and cleaved capspase-3 and caspase-9 were upregulated and the anti-apoptotic Bcl-2 was downregulated. Importantly, BBR restrained the expression of cellular PCNA, and immunofluoresence analysis of γH2AX showed that BBR increased the DNA damages induced by cisplatin. Taken together, the results demonstrated that BBR sensitized MCF-7 cells to cisplatin through induction of DNA breaks and caspase-3-dependent apoptosis. PMID:27177238

  1. [Breast cancer update].

    Science.gov (United States)

    Armuss, A

    2014-06-01

    Breast Cancer, with a life-time prevalence of about 10-12%, is the most common cancer in women. In 2013, the actress Angelina Jolie, by announcing she had a double mastectomy, increased the awareness of a family history of breast and ovarian cancer and the treatment available to reduce the inherited risks. In Germany, each year about 25 out of 100,000 women (age-standardized according to European Standard) die of the disease. The number of newly diagnosed cases is about 72,000 per year. In comparison, many other countries record higher levels. Investing in the development of new therapies has therefore been key for many years. Prevention programs, such as the mammography screening are publicly touted, in both cases with the aim to reduce breast cancer mortality. To accurately assess the risk in underwriting, it is important to know about the risk factors for the development of breast cancer, as well as the latest advances in prevention, therapy and their prognostic classification. The following article provides an overview. PMID:25000626

  2. Monitoring of tumor growth and metastasis potential in MDA-MB-435s/tk-luc human breast cancer xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Y.-F. [Department of Radiological Sciences, National Yang-Ming University, 155, Sec. 2, Li-Nong Street, Pei-tou 112, Taipei, Taiwan (China); Lin, Y.-Y. [Department of Radiological Sciences, National Yang-Ming University, 155, Sec. 2, Li-Nong Street, Pei-tou 112, Taipei, Taiwan (China); Wang, H.-E. [Department of Radiological Sciences, National Yang-Ming University, 155, Sec. 2, Li-Nong Street, Pei-tou 112, Taipei, Taiwan (China); Liu, R.-S. [Department of Nuclear Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Nuclear Medicine Department, Veterans General Hospital, Taipei, Taiwan (China); Pang Fei [Department of Veterinary Medicine, National Taiwan University, Taipei, Taiwan (China); Hwang, J.-J. [Department of Radiological Sciences, National Yang-Ming University, 155, Sec. 2, Li-Nong Street, Pei-tou 112, Taipei, Taiwan (China)]. E-mail: jjhwang@ym.edu.tw

    2007-02-01

    Molecular imaging of reporter gene expression provides a rapid, sensitive and non-invasive monitoring of tumor behaviors. In this study, we reported the establishment of a novel animal model for longitudinal examination of tumor growth kinetics and metastatic spreading in vivo. The highly metastatic human breast carcinoma MDA-MB-435s cell line was engineered to stably express herpes simplex virus type 1 thymidine kinase (HSV-1-tk) and luciferase (luc). Both {sup 131}I-FIAU and D-luciferin were used as reporter probes. For orthotopic tumor formation, MDA-MB-435s/tk-luc cells were implanted into the first nipple of 6-week-old female NOD/SCID mice. For metastatic study, cells were injected via the lateral tail vein. Mice-bearing MDA-MB-435s/tk-luc tumors were scanned for tumor growth and metastatsis using Xenogen IVIS50 system. Gamma scintigraphy and whole-body autoradiography were also applied to confirm the tumor localization. The results of bioluminescence imaging as well as histopathological finding showed that tumors could be detected in femur, spine, ovary, lungs, kidney, adrenal gland, lymph nodes and muscle at 16 weeks post i.v. injection, and correlated photons could be quantified. This MDA-MB-435s/tk-luc human breast carcinoma-bearing mouse model combined with multimodalities of molecular imaging may facilitate studies on the molecular mechanisms of cancer invasion and metastasis.

  3. Monitoring of tumor growth and metastasis potential in MDA-MB-435s/ tk-luc human breast cancer xenografts

    Science.gov (United States)

    Chang, Ya-Fang; Lin, Yi-Yu; Wang, Hsin-Ell; Liu, Ren-Shen; Pang, Fei; Hwang, Jeng-Jong

    2007-02-01

    Molecular imaging of reporter gene expression provides a rapid, sensitive and non-invasive monitoring of tumor behaviors. In this study, we reported the establishment of a novel animal model for longitudinal examination of tumor growth kinetics and metastatic spreading in vivo. The highly metastatic human breast carcinoma MDA-MB-435s cell line was engineered to stably express herpes simplex virus type 1 thymidine kinase (HSV-1- tk) and luciferase ( luc). Both 131I-FIAU and D-luciferin were used as reporter probes. For orthotopic tumor formation, MDA-MB-435s/ tk-luc cells were implanted into the first nipple of 6-week-old female NOD/SCID mice. For metastatic study, cells were injected via the lateral tail vein. Mice-bearing MDA-MB-435s/ tk-luc tumors were scanned for tumor growth and metastatsis using Xenogen IVIS50 system. Gamma scintigraphy and whole-body autoradiography were also applied to confirm the tumor localization. The results of bioluminescence imaging as well as histopathological finding showed that tumors could be detected in femur, spine, ovary, lungs, kidney, adrenal gland, lymph nodes and muscle at 16 weeks post i.v. injection, and correlated photons could be quantified. This MDA-MB-435s/ tk-luc human breast carcinoma-bearing mouse model combined with multimodalities of molecular imaging may facilitate studies on the molecular mechanisms of cancer invasion and metastasis.

  4. PIK3CA mutations are associated with decreased benefit to neoadjuvant human epidermal growth factor receptor 2-targeted therapies in breast cancer

    NARCIS (Netherlands)

    Majewski, Ian J; Nuciforo, Paolo; Mittempergher, Lorenza; Bosma, Astrid J; Eidtmann, Holger; Holmes, Eileen; Sotiriou, Christos; Fumagalli, Debora; Jimenez, Jose; Aura, Claudia; Prudkin, Ludmila; Díaz-Delgado, Maria Carmen; de la Peña, Lorena; Loi, Sherene; Ellis, Catherine; Schultz, Nikolaus; de Azambuja, Evandro; Harbeck, Nadia; Piccart-Gebhart, Martine; Bernards, René; Baselga, José

    2015-01-01

    PURPOSE: We investigated whether mutations in the gene encoding the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) correlates with response to neoadjuvant human epidermal growth factor receptor 2 (HER2) -targeted therapies in patients with breast cancer. PATIENTS AND METHODS: Baseli

  5. Epidemiology of basal-like breast cancer

    OpenAIRE

    Millikan, Robert C.; Newman, Beth; Tse, Chiu-Kit; Moorman, Patricia G.; Conway, Kathleen; Smith, Lisa. V.; Labbok, Miriam H; Geradts, Joseph; Bensen, Jeannette T.; Jackson, Susan; Nyante, Sarah; Livasy, Chad; Carey, Lisa; Earp, H. Shelton; Perou, Charles M

    2007-01-01

    Risk factors for the newly identified “intrinsic” breast cancer subtypes (luminal A, luminal B, basal-like and human epidermal growth factor receptor 2-positive/estrogen receptor-negative) were determined in the Carolina Breast Cancer Study, a population-based, case–control study of African-American and white women. Immunohistochemical markers were used to subtype 1,424 cases of invasive and in situ breast cancer, and case subtypes were compared to 2,022 controls. Luminal A, the most common s...

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

    OpenAIRE

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

    2013-01-01

    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-...

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    2016-03-01

    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

  9. Data on alteration of hormone and growth factor receptor profiles over progressive passages of breast cancer cell lines representing different clinical subtypes.

    Science.gov (United States)

    Nair, Madhumathy G; Desai, Krisha; Prabhu, Jyothi S; Hari, P S; Remacle, Jose; Sridhar, T S

    2016-09-01

    Human breast cancers are a highly heterogeneous group of tumours consisting of several molecular subtypes with a variable profile of hormone, growth factor receptors and cytokeratins [1]. Here, the data shows immunofluorescence profiling of four different cell lines belonging to distinct clinical subtypes of breast cancer. Post revival, the cell lines were passaged in culture and immunophenotyping was done for ER, HER-2, AR and EGFR. Data for the markers from early passage (5th) through passages as late as 25 for the different cell lines is presented. PMID:27508248

  10. Conjugated docosahexaenoic acid suppresses KPL-1 human breast cancer cell growth in vitro and in vivo: potential mechanisms of action

    International Nuclear Information System (INIS)

    The present study was conducted to examine the effect of conjugated docosahexaenoic acid (CDHA) on cell growth, cell cycle progression, mode of cell death, and expression of cell cycle regulatory and/or apoptosis-related proteins in KPL-1 human breast cancer cell line. This effect of CDHA was compared with that of docosahexaenoic acid (DHA). KPL-1 cell growth was assessed by colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; cell cycle progression and mode of cell death were examined by flow cytometry; and levels of expression of p53, p21Cip1/Waf1, cyclin D1, Bax, and Bcl-2 proteins were examined by Western blotting analysis. In vivo tumor growth was examined by injecting KPL-1 cells subcutaneously into the area of the right thoracic mammary fat pad of female athymic mice fed a CDHA diet. CDHA inhibited KPL-1 cells more effectively than did DHA (50% inhibitory concentration for 72 hours: 97 μmol/l and 270 μmol/l, respectively). With both CDHA and DHA growth inhibition was due to apoptosis, as indicated by the appearance of a sub-G1 fraction. The apoptosis cascade involved downregulation of Bcl-2 protein; Bax expression was unchanged. Cell cycle progression was due to G0/G1 arrest, which involved increased expression of p53 and p21Cip1/Waf1, and decreased expression of cyclin D1. CDHA modulated cell cycle regulatory proteins and apoptosis-related proteins in a manner similar to that of parent DHA. In the athymic mouse system 1.0% dietary CDHA, but not 0.2%, significantly suppressed growth of KPL-1 tumor cells; CDHA tended to decrease regional lymph node metastasis in a dose dependent manner. CDHA inhibited growth of KPL-1 human breast cancer cells in vitro more effectively than did DHA. The mechanisms of action involved modulation of apoptosis cascade and cell cycle progression. Dietary CDHA at 1.0% suppressed KPL-1 cell growth in the athymic mouse system

  11. Hypoxia-inducible factor 1α promotes primary tumor growth and tumor-initiating cell activity in breast cancer

    OpenAIRE

    Schwab, Luciana P; Peacock, Danielle L.; Majumdar, Debeshi; Ingels, Jesse F; Jensen, Laura C; Smith, Keisha D; Cushing, Richard C; Seagroves, Tiffany N

    2012-01-01

    Introduction Overexpression of the oxygen-responsive transcription factor hypoxia-inducible factor 1α (HIF-1α) correlates with poor prognosis in breast cancer patients. The mouse mammary tumor virus polyoma virus middle T (MMTV-PyMT) mouse is a widely utilized preclinical mouse model that resembles human luminal breast cancer and is highly metastatic. Prior studies in which the PyMT model was used demonstrated that HIF-1α is essential to promoting carcinoma onset and lung metastasis, although...

  12. Transforming growth factor-β1 regulates epithelial-mesenchymal transition in association with cancer stem-like cells in a breast cancer cell line

    OpenAIRE

    Jia, Yongfeng; Wu, Di; Yun, Fen; Shi, Lin; Luo, Nianrong; Liu, Zhiyue; Shi, Yonghong; Sun, Qinnuan; Jiang, Lili; Wang, Shiqi; Du, Maolin

    2014-01-01

    Epithelial-mesenchymal transition (EMT) is associated with altered connection and junctions between cells and changes in abilities of invasion and migration. In this study, we investigated whether SK-BR-3 breast cancer cells induced to undergo EMT exhibit changes in morphological and invasion abilities after Transforming growth factor β1 (TGF-β1) treatment. Serum-deprived SK-BR-3 cells were treated with TGF-β1 (0, 10 ng/mL) for 24 h. The cells morphological changes were observed and imaged us...

  13. Breast Cancer in Art Painting

    OpenAIRE

    Forma Ewa; Bernaciak Magdalena; Bryś Magdalena

    2011-01-01

    Breast cancer is an emotive cancer. It is a disease that affects a visible sexual organ and it is the commonest single cause of death of women between 40 and 60 years of age. Nevertheless, this type of cancer was infrequently depicted in art paintings. In this article the themes from the breast cancer in famous art paintings are discussed.

  14. Period-2: a tumor suppressor gene in breast cancer

    OpenAIRE

    Xiang, Shulin; Coffelt, Seth B.; Mao, Lulu; Yuan, Lin; Cheng, Qi; Hill, Steven M

    2008-01-01

    Previous reports have suggested that the ablation of the Period 2 gene (Per 2) leads to enhanced development of lymphoma and leukemia in mice. Employing immunoblot analyses, we have demonstrated that PER 2 is endogenously expressed in human breast epithelial cell lines but is not expressed or is expressed at significantly reduced level in human breast cancer cell lines. Expression of PER 2 in MCF-7 breast cancer cells significantly inhibited the growth of MCF-7 human breast cancer cells, and,...

  15. Breast Cancer - Early Diagnosis

    Centers for Disease Control (CDC) Podcasts

    2011-04-28

    This podcast answers a listener's question about how to tell if she has breast cancer.  Created: 4/28/2011 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 4/28/2011.

  16. Hereditary breast cancer

    DEFF Research Database (Denmark)

    Larsen, Martin J; Thomassen, Mads; Gerdes, Anne-Marie;

    2014-01-01

    Pathogenic mutations in BRCA1 or BRCA2 are only detected in 25% of families with a strong history of breast cancer, though hereditary factors are expected to be involved in the remaining families with no recognized mutation. Molecular characterization is expected to provide new insight into the t......Pathogenic mutations in BRCA1 or BRCA2 are only detected in 25% of families with a strong history of breast cancer, though hereditary factors are expected to be involved in the remaining families with no recognized mutation. Molecular characterization is expected to provide new insight...... into the tumor biology to guide the search of new high-risk alleles and provide better classification of the growing number of BRCA1/2 variants of unknown significance (VUS). In this review, we provide an overview of hereditary breast cancer, its genetic background, and clinical implications, before focusing...... on the pathologically and molecular features associated with the disease. Recent transcriptome and genome profiling studies of tumor series from BRCA1/2 mutation carriers as well as familial non-BRCA1/2 will be discussed. Special attention is paid to its association with molecular breast cancer subtypes as well...

  17. Breast Cancer and Fatigue

    OpenAIRE

    Bardwell, Wayne A; Ancoli-Israel, Sonia

    2008-01-01

    Fatigue is a common and disabling symptom in breast cancer patients and survivors. A rather nebulous concept, fatigue overlaps with sleepiness and depressed mood. In this chapter, we cover methods for assessing fatigue; describe the occurrence of fatigue before, during and after initial treatment; present possible underlying mechanisms of fatigue; and, enumerate approaches to its treatment.

  18. Prostate cancer is not breast cancer

    Directory of Open Access Journals (Sweden)

    Ajit Venniyoor

    2016-01-01

    Full Text Available Cancers of the prostate and breast are hormone dependent cancers. There is a tendency to equate them and apply same algorithms for treatment. It is pointed out that metastatic prostate cancer with bone-only disease is a potentially fatal condition with a much poorer prognosis than metastatic breast cancer and needs a more aggressive approach.

  19. Prostate cancer is not breast cancer

    OpenAIRE

    Ajit Venniyoor

    2016-01-01

    Cancers of the prostate and breast are hormone dependent cancers. There is a tendency to equate them and apply same algorithms for treatment. It is pointed out that metastatic prostate cancer with bone-only disease is a potentially fatal condition with a much poorer prognosis than metastatic breast cancer and needs a more aggressive approach.

  20. N-3 poly-unsaturated fatty acids shift estrogen signaling to inhibit human breast cancer cell growth.

    Directory of Open Access Journals (Sweden)

    Wenqing Cao

    Full Text Available Although evidence has shown the regulating effect of n-3 poly-unsaturated fatty acid (n-3 PUFA on cell signaling transduction, it remains unknown whether n-3 PUFA treatment modulates estrogen signaling. The current study showed that docosahexaenoic acid (DHA, C22:6, eicosapentaenoic acid (EPA, C20:5 shifted the pro-survival and proliferative effect of estrogen to a pro-apoptotic effect in human breast cancer (BCa MCF-7 and T47D cells. 17 β-estradiol (E2 enhanced the inhibitory effect of n-3 PUFAs on BCa cell growth. The IC50 of DHA or EPA in MCF-7 cells decreased when combined with E2 (10 nM treatment (from 173 µM for DHA only to 113 µM for DHA+E2, and from 187 µm for EPA only to 130 µm for EPA+E2. E2 also augmented apoptosis in n-3 PUFA-treated BCa cells. In contrast, in cells treated with stearic acid (SA, C18:0 as well as cells not treated with fatty acid, E2 promoted breast cancer cell growth. Classical (nuclear estrogen receptors may not be involved in the pro-apoptotic effects of E2 on the n-3 PUFA-treated BCa cells because ERα agonist failed to elicit, and ERα knockdown failed to block E2 pro-apoptotic effects. Subsequent studies reveal that G protein coupled estrogen receptor 1 (GPER1 may mediate the pro-apoptotic effect of estrogen. N-3 PUFA treatment initiated the pro-apoptotic signaling of estrogen by increasing GPER1-cAMP-PKA signaling response, and blunting EGFR, Erk 1/2, and AKT activity. These findings may not only provide the evidence to link n-3 PUFAs biologic effects and the pro-apoptotic signaling of estrogen in breast cancer cells, but also shed new insight into the potential application of n-3 PUFAs in BCa treatment.

  1. Progestins and breast cancer.

    Science.gov (United States)

    Pasqualini, Jorge R

    2007-10-01

    Progestins exert their progestational activity by binding to the progesterone receptor (form A, the most active and form B, the less active) and may also interact with other steroid receptors (androgen, glucocorticoid, mineralocorticoid, estrogen). They can have important effects in other tissues besides the endometrium, including the breast, liver, bone and brain. The biological responses of progestins cover a very large domain: lipids, carbohydrates, proteins, water and electrolyte regulation, hemostasis, fibrinolysis, and cardiovascular and immunological systems. At present, more than 200 progestin compounds have been synthesized, but the biological response could be different from one to another depending on their structure, metabolism, receptor affinity, experimental conditions, target tissue or cell line, as well as the biological response considered. There is substantial evidence that mammary cancer tissue contains all the enzymes responsible for the local biosynthesis of estradiol (E(2)) from circulating precursors. Two principal pathways are implicated in the final steps of E(2) formation in breast cancer tissue: the 'aromatase pathway', which transforms androgens into estrogens, and the 'sulfatase pathway', which converts estrone sulfate (E(1)S) into estrone (E(1)) via estrone sulfatase. The final step is the conversion of weak E(1) to the potent biologically active E(2) via reductive 17beta-hydroxysteroid dehydrogenase type 1 activity. It is also well established that steroid sulfotransferases, which convert estrogens into their sulfates, are present in breast cancer tissues. It has been demonstrated that various progestins (e.g. nomegestrol acetate, medrogestone, promegestone) as well as tibolone and their metabolites can block the enzymes involved in E(2) bioformation (sulfatase, 17beta-hydroxysteroid dehydrogenase) in breast cancer cells. These substances can also stimulate the sulfotransferase activity which converts estrogens into the biologically

  2. Factors affecting disease-free survival in patients with human epidermal growth factor receptor 2-positive breast cancer who receive adjuvant trastuzumab

    Science.gov (United States)

    GÜNDÜZ, SEYDA; GÖKSU, SEMA SEZGIN; ARSLAN, DENIZ; TATLI, ALI MURAT; UYSAL, MÜKREMIN; GÜNDÜZ, UMUT RIZA; SEVINÇ, MERT MAHSUNI; COŞKUN, HASAN SENOL; BOZCUK, HAKAN; MUTLU, HASAN; SAVAS, BURHAN

    2015-01-01

    Breast cancer is the most frequently diagnosed cancer in women worldwide and the second cause of cancer-related mortality. A total of 20–30% of patients with early-stage breast cancer develop recurrence within the first 5 years following diagnosis. Trastuzumab significantly improves overall survival and disease-free survival (DFS) in women with human epidermal growth factor receptor 2 (HER2)-positive early and locally advanced breast cancer. This study aimed to determine the factors that affect DFS following adjuvant transtuzumab therapy. A total of 62 patients treated with trastuzumab for early and locally advanced breast cancer were included in our study. Data, including pathology, treatment and treatment outcome, rate of recurrence and laboratory tests, were retrospectively collected. There was no significant association between DFS and age, menopausal status, disease stage and hormone receptor status. The median follow-up was 48.4 months. The median DFS of patients treated with adjuvant trastuzumab was 64.1 months. In addition, the median DFS was 44.3 vs. 66.8 months in patients with platelet-lymphocyte ratio (PLR) ≤200 vs. >200, respectively (log-rank test; P=0.001), and 70 vs. 45 months in patients with eosinophil count ≤70 vs. >70×103/mm3 (log-rank test; P=0.001). Our data revealed the prognostic relevance of a decrease in the peripheral blood eosinophil count and PLR value following trastuzumab therapy in breast cancer. PLR and eosinophil count measurements are cost-effective, readily available worldwide, non-invasive and safe. Combined with other markers, such as patient age, tumor stage and tumor histology, may be effectively used for patients with breast cancer. PMID:26623060

  3. Alpha-linolenic acid regulates the growth of breast and cervical cancer cell lines through regulation of NO release and induction of lipid peroxidation

    Directory of Open Access Journals (Sweden)

    Ruchika Kaul-Ghanekar

    2013-02-01

    Full Text Available In the present work, we have analyzed the effect of the essential fatty acid, alpha linolenic acid (ALA on nitric oxide release as well as induction of lipid peroxidation in breast (MCF-7 and MDA-MB-231 and cervical (SiHa and HeLa cancer cell lines. ALA-treated cells showed a dose-dependent decrease in cell viability in both breast and cervical cancer cell lines without affecting the viability of non-cancerous transformed HEK 293 cells. Both types of cancer cells treated with ALA demonstrated a significant reduction in nitric oxide (NO release with a simultaneous increase in lipid peroxidation (LPO. This was followed by a decrease in the mitochondrial membrane potential as well as activation of caspase 3 leading to apoptosis. Thus, ALA regulated the growth of cancer cell lines through induction of lipid peroxidation and modulation of nitric oxide release resulting in apoptosis.

  4. Visualising dual downregulation of insulin-like growth factor receptor-1 and vascular endothelial growth factor-A by heat shock protein 90 inhibition effect in triple negative breast cancer

    NARCIS (Netherlands)

    Terwisscha Van Scheltinga, Anton G. T.; Berghuis, Paul; Nienhuis, Hilde H.; Timmer-Bosscha, Hetty; Pot, Linda; Gaykema, Sietske B. M.; Lub-de Hooge, Marjolijn N.; Kosterink, Jos G. W.; de Vries, Elisabeth G. E.; Schroder, Carolien P.

    2014-01-01

    Purpose: Triple negative breast cancer (TNBC) is biologically characterised by heterogeneous presence of molecular pathways underlying it. Insulin-like growth factor receptor-1 (IGF-1R) expression and vascular endothelial growth factor-A (VEGF-A) have been identified as key factors in these pathways

  5. Endocrine therapy of breast cancer

    International Nuclear Information System (INIS)

    This book results from a meeting of the ESO (European School of Oncology) Task Force on endocrine aspects of breast cancer. The contributions stem from some of the most outstanding researchers in Europe and highlight mainly methodological issues and new avenues for future research. The chapters on basic research deal primarily with experimental strategies for studying the relationship between steroid hormones, growth factors, and oncongenes. The clinically oriented chapters treat the methodology of clinical trials. Provocative questions are raised, such as: What are the pitfalls in endocrine trials? What does statistical proof mean? How can we consider a quality of life endpoint in the adjuvant setting? Two special reports deal with the controversial issues of chemoprevention in high-risk normal women and the optimization of the hormonal contribution to the adjuvant therapy of breast cancer. Topics considered included oncogenic transformations, radiotherapy, steroid hormones, cell proliferation, tamoxifen, and preventive medicine

  6. Early diagnosis of breast cancer

    International Nuclear Information System (INIS)

    Modern data are presentd on epidemology etiopathogensis and statistics of breast cancer. Home and international clinical and histological classifications is given. Much attention is paid to the methods for early diagnosis of pretumor diseases and breast cancer: clinical roentgenomammography, thrmography and computerized tomomammography. The role of self-examination in cancer early detection has been analyzed. Special attention is paid to system of detection of minimal and unpalpable form of breast cancer, screening of these tumors. 113 refs.; 60 figs.; 6 tabs

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

    Science.gov (United States)

    2016-06-23

    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

  8. Breast cancer surveillance.

    Science.gov (United States)

    Rachetta, Eleonora; Osano, Silvia; Astegiano, Francesco; Martincich, Laura

    2016-10-01

    Since several studies have demonstrated the inadequate diagnostic performance of mammography in high risk women, over the past two decades, different breast imaging tests have been evaluated as additional diagnostic methods to mammography, and the most relevant ones are the techniques that do not imply the use of X-rays, considering the young age of these patients and the higher radio-sensitivity. Breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has risen growing interest not only because of the absence of use of X-rays, but also because it provides morpho-functional features, which may depict biological characteristics of breast tissues, including invasive and in situ cancers. Different multicenter non-randomized prospective studies aimed to evaluate breast DCE-MRI as an integral part of surveillance programs, agreed about the evidence that in high risk women screening with DCE-MRI is more effective than either mammography and/or ultrasound. Moreover, this modality leads to the identifications of cancers at a more favorable stage, allowing a real advantage in terms of tumor size and nodal involvement. The medical community is evaluating to suggest DCE-MRI alone as screening modality in high-risk women, as it was reported that in these cases the sensitivity of MRI plus conventional imaging was not significantly higher than that of MRI alone. Breast MRI is now recommended as part of screening program for high risk women by both European and American guidelines. PMID:26924173

  9. Opioids and breast cancer recurrence

    DEFF Research Database (Denmark)

    Cronin-Fenton, Deirdre P; Heide-Jørgensen, Uffe; Ahern, Thomas P;

    2015-01-01

    BACKGROUND: Opioids may alter immune function, thereby potentially affecting cancer recurrence. The authors investigated the association between postdiagnosis opioid use and breast cancer recurrence. METHODS: Patients with incident, early stage breast cancer who were diagnosed during 1996 through...... 2008 in Denmark were identified from the Danish Breast Cancer Cooperative Group Registry. Opioid prescriptions were ascertained from the Danish National Prescription Registry. Follow-up began on the date of primary surgery for breast cancer and continued until breast cancer recurrence, death......, emigration, 10 years, or July 31, 2013, whichever occurred first. Cox regression models were used to compute hazard ratios and 95% confidence intervals associating breast cancer recurrence with opioid prescription use overall and by opioid type and strength, immunosuppressive effect, chronic use (≥6 months...

  10. Kin-cohort estimates for familial breast cancer risk in relation to variants in DNA base excision repair, BRCA1 interacting and growth factor genes

    International Nuclear Information System (INIS)

    Subtle functional deficiencies in highly conserved DNA repair or growth regulatory processes resulting from polymorphic variation may increase genetic susceptibility to breast cancer. Polymorphisms in DNA repair genes can impact protein function leading to genomic instability facilitated by growth stimulation and increased cancer risk. Thus, 19 single nucleotide polymorphisms (SNPs) in eight genes involved in base excision repair (XRCC1, APEX, POLD1), BRCA1 protein interaction (BRIP1, ZNF350, BRCA2), and growth regulation (TGFß1, IGFBP3) were evaluated. Genomic DNA samples were used in Taqman 5'-nuclease assays for most SNPs. Breast cancer risk to ages 50 and 70 were estimated using the kin-cohort method in which genotypes of relatives are inferred based on the known genotype of the index subject and Mendelian inheritance patterns. Family cancer history data was collected from a series of genotyped breast cancer cases (N = 748) identified within a cohort of female US radiologic technologists. Among 2,430 female first-degree relatives of cases, 190 breast cancers were reported. Genotypes associated with increased risk were: XRCC1 R194W (WW and RW vs. RR, cumulative risk up to age 70, risk ratio (RR) = 2.3; 95% CI 1.3–3.8); XRCC1 R399Q (QQ vs. RR, cumulative risk up to age 70, RR = 1.9; 1.1–3.9); and BRIP1 (or BACH1) P919S (SS vs. PP, cumulative risk up to age 50, RR = 6.9; 1.6–29.3). The risk for those heterozygous for BRCA2 N372H and APEX D148E were significantly lower than risks for homozygotes of either allele, and these were the only two results that remained significant after adjusting for multiple comparisons. No associations with breast cancer were observed for: APEX Q51H; XRCC1 R280H; IGFPB3 -202A>C; TGFß1 L10P, P25R, and T263I; BRCA2 N289H and T1915M; BRIP1 -64A>C; and ZNF350 (or ZBRK1) 1845C>T, L66P, R501S, and S472P. Some variants in genes within the base-excision repair pathway (XRCC1) and BRCA1 interacting proteins (BRIP1) may play a role

  11. MicroRNA-154 inhibits growth and invasion of breast cancer cells through targeting E2F5

    Science.gov (United States)

    Xu, Hui; Fei, Dan; Zong, Shan; Fan, Zhimin

    2016-01-01

    Accumulating evidence suggested that microRNA-154 (miR-154) might play important roles in the development of various cancer types. However, the role of miR-154 in breast cancer progression remains largely unknown. Here, miR-154 expression level was measured via quantitative real-time RT-PCR (qRT-PCR) in 36 pairs of human breast cancer tissues and adjacent normal breast tissues and in a panel of human breast cancer cell lines. Cell proliferation, cycle, migration, and invasion were assessed by CCK8 assay, flow cytometer assay, wound healing assay and transwell invasion assay, respectively. Luciferase reporter assay and Western blot was used to verify E2F transcription factor 5 protein (E2F5) as a novel target gene of miR-154. Our results showed that miR-154 was frequently downregulated in breast cancer tissues and cell lines. Overexpression of miR-154 in MCF-7 cells significantly inhibited cell proliferation, migration, and invasion, and increased cell arrest at G0/G1 stage in vitro. E2F5 was identified as a target of miR-154, and its expression was inversely correlated with miR-154 expression in clinical breast cancer tissues. In addition, downregulation of E2F5 in MCF7 cells had similar effect on cell proliferation, cycle, migration and invasion by miR-154 induced. These findings indicate that miR-154 acts as a tumor suppressor by targeting E2F5, suggesting miR-154 as a potential therapeutic target for the treatment of breast cancer. PMID:27398145

  12. Ganodermanontriol (GDNT) exerts its effect on growth and invasiveness of breast cancer cells through the down-regulation of CDC20 and uPA.

    Science.gov (United States)

    Jiang, Jiahua; Jedinak, Andrej; Sliva, Daniel

    2011-11-18

    Ganoderma lucidum is a medicinal mushroom that has been recognized by Traditional Chinese Medicine (TCM). Although some of the direct anticancer activities are attributed to the presence of triterpenes-ganoderic and lucidenic acids-the activity of other compounds remains elusive. Here we show that ganodermanontriol (GDNT), a Ganoderma alcohol, specifically suppressed proliferation (anchorage-dependent growth) and colony formation (anchorage-independent growth) of highly invasive human breast cancer cells MDA-MB-231. GDNT suppressed expression of the cell cycle regulatory protein CDC20, which is over-expressed in precancerous and breast cancer cells compared to normal mammary epithelial cells. Moreover, we found that CDC20 is over-expressed in tumors when compared to the tissue surrounding the tumor in specimens from breast cancer patients. GDNT also inhibited invasive behavior (cell adhesion, cell migration, and cell invasion) through the suppression of secretion of urokinase-plasminogen activator (uPA) and inhibited expression of uPA receptor. In conclusion, mushroom GDNT is a natural agent that has potential as a therapy for invasive breast cancers. PMID:22033405

  13. Stable RNA interference of ErbB-2 gene synergistic with epirubicin suppresses breast cancer growth in vitro and in vivo

    International Nuclear Information System (INIS)

    Overexpression of human epidermal growth factor receptor-2 (Her2, ErbB-2) contributes to the progression and metastasis of breast cancer, implying that Her2 gene is a suitable target of RNA interference (RNAi) for breast cancer therapy. Here, we employed plasmid-mediated expression of 2 different Her2-shRNAs (pU6-Her2shRNAs) efficiently silenced the target gene expression on Her2 expressing SKBR-3 breast cancer cells in both mRNA and protein levels. Consequently, pU6-Her2shRNA increased apoptosis and reduced proliferation of SKBR-3 cells assayed by TUNEL and MTT, respectively. In vivo, intra-tumor injection of pU6-Her2shRNA inhibited the growth of SKBR-3 tumors inoculated subcutaneously in nude mice. Furthermore, pU6-Her2shRNA synergized the tumor suppression effect of epirubicin to SKBR-3 cells in vitro and implanted subcutaneously in nude mice. Therefore, we concluded that stable silencing of Her2 gene expression with plasmid expressing shRNA may hold great promise as a novel therapy for Her2 expressing breast cancers alone or in combination with anthracycline chemotherapy

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

    Science.gov (United States)

    2016-01-12

    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

  15. Abortion, Miscarriage, and Breast Cancer Risk

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Abortion, Miscarriage, and Breast Cancer Risk A woman’s hormone ... be conducted to determine whether having an induced abortion, or a miscarriage (also known as spontaneous abortion), ...

  16. You, Your Teenage Daughter and Breast Cancer.

    Science.gov (United States)

    Brateman, Libby

    1991-01-01

    Discusses breast cancer and teenagers, focusing on how parents can introduce the subject and encourage breast self-examination. The article provides information on breast cancer statistics, mammography, and American Cancer Society services. (SM)

  17. Molecular imaging of breast cancer

    NARCIS (Netherlands)

    Adams, A.L.L.

    2014-01-01

    Breast cancer is the most common type of cancer in women. Imaging techniques play a pivotal role in breast cancer management, especially in lesion detection, treatment planning and evaluation, and prognostication. These imaging techniques have however limitations such as the use of ionizing radiatio

  18. Correlation between the expression of vascular endothelial growth factor c and C-erbB-2 in human breast cancer

    Institute of Scientific and Technical Information of China (English)

    Shuxian Qu; Zhendong Zheng; Zhaozhe Liu; Liang Liu; Miao Zhang; Yaling Han; Xiaodong Xie

    2014-01-01

    Objective: We aimed to study the transcription level of VEGF-C in human breast cancer tissue, and explore the correlations with the expression of C-erbB-2.Methods: The expression of VEGF-C mRNA in 51 cases of human breast cancer was assessed by hybridization in situ. The expressions of C-erbB-2 was assessed by immunohistochemistry.Results:The positive rate of VEGF-C mRNA was 54.9% in 51 cases of breast cancer. The transcription level had correlation with tumor size and status of lymph nodes (P < 0.05). The expression of VEGF-C mRNA had a positive correlation with the expression of C-erbB-2 (P < 0.05).Conclusion: The up-expression of VEGF-C has a significant correlation with the malignancy level and clinical stage of breast cancer. The combined detection of VEGF-C, C-erbB-2 may help to estimate the prognosis of patients with breast cancer and study on thetherapeutic implications.

  19. Tamoxifen Resistance in Breast Cancer

    OpenAIRE

    Chang, Minsun

    2012-01-01

    Tamoxifen is a central component of the treatment of estrogen receptor (ER)-positive breast cancer as a partial agonist of ER. It has been clinically used for the last 30 years and is currently available as a chemopreventive agent in women with high risk for breast cancer. The most challenging issue with tamoxifen use is the development of resistance in an initially responsive breast tumor. This review summarizes the roles of ER as the therapeutic target of tamoxifen in cancer treatment, clin...

  20. Green Tea and Breast Cancer

    OpenAIRE

    Wu, Anna H.; Butler, Lesley M.

    2011-01-01

    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 stud...

  1. Differential effects of angiostatin, endostatin and interferon-alpha(1) gene transfer on in vivo growth of human breast cancer cells.

    Science.gov (United States)

    Indraccolo, S; Gola, E; Rosato, A; Minuzzo, S; Habeler, W; Tisato, V; Roni, V; Esposito, G; Morini, M; Albini, A; Noonan, D M; Ferrantini, M; Amadori, A; Chieco-Bianchi, L

    2002-07-01

    The administration of different angiogenesis inhibitors by gene transfer has been shown to result in inhibition of tumor growth in animal tumor models, but the potency of these genes has been only partially evaluated in comparative studies to date. To identify the most effective anti-angiogenic molecule for delivery by retroviral vectors, we investigated the effects of angiostatin, endostatin and interferon(IFN)-alpha(1) gene transfer in in vivo models of breast cancer induced neovascularization and tumor growth. Moloney leukemia virus-based retroviral vectors for expression of murine angiostatin, endostatin and IFN-alpha(1) were generated, characterized, and used to transduce human breast cancer cell lines (MCF7 and MDA-MB435). Secretion of the recombinant proteins was confirmed by biological and Western blotting assays. Their production did not impair in vitro growth of these breast cancer cells nor their viability, and did not interfere with the expression of angiogenic factors. However, primary endothelial cell proliferation and migration in vitro were inhibited by supernatants of the transduced cells containing angiostatin, endostatin, and IFN-alpha(1). Stable gene transfer of the IFN-alpha(1) cDNA by retroviral vectors in both MCF7 and MDA-MB435 cells resulted in a marked and long-lasting inhibition of tumor growth in nude mice that was associated with reduced vascularization. Endostatin reduced the in vivo growth of MDA-MB435, but not MCF7 cells, despite similar levels of in vivo production, and angiostatin did not impair the in vivo growth of either cell line. These findings indicate heterogeneity in the therapeutic efficacy of angiostatic molecules delivered by viral vectors and suggest that gene therapy with IFN-alpha(1) and endostatin might be useful for treatment of breast cancer. PMID:12080381

  2. CaCO3/CaIP6 composite nanoparticles effectively deliver AKT1 small interfering RNA to inhibit human breast cancer growth

    Directory of Open Access Journals (Sweden)

    Zhou H

    2015-07-01

    Full Text Available Hongyan Zhou,1,* Jinhuan Wei,2,* Qiangsheng Dai,3 Liping Wang,4 Junhang Luo,2 Tuckyun Cheang,4 Shenming Wang4 1Department of Neurological Intensive Care Unit, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 3Department of Oncology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 4Department of Breast Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: Small interfering RNA (siRNA-mediated gene therapy is a promising strategy to temporarily inhibit the expression of genes involved in development of breast cancer. The lack of a safe and efficient gene delivery system has become a major hurdle for siRNA-mediated gene therapy in breast cancer. Our previous studies have demonstrated that inorganic amorphous calcium carbonate (ACC hybrid nanospheres functionalized with CaIP6 (ACC/CaIP6 nanoparticles are an efficient nucleic acid delivery tool. The present study aimed to evaluate the safety and efficiency of ACC/CaIP6 in delivering siRNA targeting AKT1 (siAKT1 for the treatment of breast cancer. Methods: The cytotoxicity of the ACC/CaIP6 nanoparticles was evaluated using a tetrazolium assay. The transfection efficiency and intracellular distribution of ACC/siAKT1 were analyzed by flow cytometry and confocal laser scanning microscopy, respectively. A series of in vitro and in vivo assays was performed to evaluate the effects of ACC/CaIP6/siAKT1 on growth of breast cancer cells. Results: ACC/CaIP6 nanoparticles effectively transfected cells with little or no toxicity. AKT1 knockdown by ACC/CaIP6/siAKT1 inhibited cell cycle progression and promoted apoptosis of MCF-7 cells. Intratumoral injection of ACC/CaIP6/siAKT1 significantly suppressed the

  3. Dosimetry of breast cancer

    International Nuclear Information System (INIS)

    The systemic therapy of breast cancer has also changed profoundly during the last 60 years, and in this time the integration of treatment modalities involve a major area of investigation. The dosimetry of breast cancer presents different complications which can range from the Physician's handling of the neoplasia up to the simple aspects of physical simulation, contour design, radiation fields, irregular surfaces and computer programs containing mathematical equations which differ little or largely with the reality of the radiation distribution into the volume to be irradiated. We have studied the problem using two types of measurements to determine how the radiation distribution is in irregular surfaces, and designing an easier skill to be used with each patient, in order to optimize the treatment with respect to the simulation and verification process. (author). 7 refs

  4. Estrogens and breast cancer

    Directory of Open Access Journals (Sweden)

    HANKINSON SUSAN E

    1997-01-01

    Full Text Available In this review, we summarize the epidemiologic evidence for the associations of oral contraceptives and postmenopausal hormones with risk of breast cancer. We also describe the biologic plausibility of these relationships. Overall, there appears to be little, if any, increase in risk with oral contraceptive use in general, even among users for 10 or more years. However, compared to never users, current oral contraceptive users appear to have a modest elevation in risk that subsides within about 10 years after cessation of use. For postmenopausal hormones, the weight of the evidence suggests little or no increase in risk among users of short duration, or for use in the past. However, current longer term use is associated with an increased risk of breast cancer that increases with duration. This increase in risk is large enough, and well enough supported, to be considered along with the other risks and benefits of postmenopausal hormone therapy.

  5. An alternative approach for treatment of breast cancer.

    Science.gov (United States)

    Swartzendruber, D E; Retsky, M W; Wardwell, R H; Bame, P D

    1994-01-01

    Since adjuvant chemotherapy and hormonal therapy generally extend disease free survival in breast cancer rather than provide a cure, we have examined the current breast cancer paradigm. Heterogeneity is a fundamental characteristic of breast cancer tissue and a well recognized aspect of the disease. There are variations in natural history, histopathology, biochemistry and endocrinology, and molecular biology of cancer tissues and cells within the tissues. A variety of data indicate that growth kinetics are also variable, not only from tumor to tumor, but also during the natural history of an individual's tumor. To better understand kinetic heterogeneity, a stochastic numeric computer model of the natural history of breast cancer has been developed. To be consistent with inter- and intratumor kinetic heterogeneity and with late relapse, the model predicts that tumors grow in an irregular fashion with alternating periods of growth and periods of dormancy rather than the generally accepted modified exponential, or Gompertzian fasion. The prediction of irregular growth has been compared to data relevant to growth characteristics of human breast cancer. Much data support the concept of irregular kinetics and temporary dormancy rather than steady, Gompertzian growth of human breast cancer. Thus, in addition to drug resistance, kinetic heterogeneity may help explain the limited impact that traditional chemotherpeutic treatment has had on mortality from breast cancer. Although the mechanisms underlying irregular growth need to be better understood, non-Gompertzian growth kinetics indicates that there may be alternative approaches for breast cancer treatment. PMID:7865858

  6. Role of ornithine decarboxylase in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Wensheng Deng; Xian Jiang; Yu Mei; Jingzhong Sun; Rong Ma; Xianxi Liu; Hui Sun; Hui Tian; Xueying Sun

    2008-01-01

    Ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis that decarboxylates ornithine to putrescine, has become a promising target for cancer research. The aim of this study is to investigate the role of ODC in breast cancer. We detected expression of ODC in breast cancer tissues and four breast cancer cell lines, and transfected breast cancer cells with an adenoviral vector carrying antisense ODC (rAd-ODC/Ex3as) and examined their growth and migration.ODC was overexpressed in breast cancer tissues and cell lines compared with non-tumor tissues and normal breast epithelial celis,and there was a positive correlation between the level of ODC mRNA and the staging of tumors.The expression of ODC correlated with cyclin D1,a cell cycle protein,in synchronized breast cancer MDA-MB-231 cells.Gene transfection of rAd-ODC/Ex3as markedly down-regulated expression Of ODC and cyclin D1,resulting in suppression of proliferation and cell cycle arrest at G0-G1 phase,and the inhibifion of colony formation,an anchorage-independent growth pattern,and the migratory ability of MDA-MB-231 cells.rAd-ODC/Ex3as also markedly reduced the concentration of putrescine,but not spermidine or spermine,in MDA-MB-231 cells.The results suggested that the ODC gene might act as aprognostic factor for breast cancer and it could be a promising therapeutic target.

  7. Proteomic classification of breast cancer.

    LENUS (Irish Health Repository)

    Kamel, Dalia

    2012-11-01

    Being a significant health problem that affects patients in various age groups, breast cancer has been extensively studied to date. Recently, molecular breast cancer classification has advanced significantly with the availability of genomic profiling technologies. Proteomic technologies have also advanced from traditional protein assays including enzyme-linked immunosorbent assay, immunoblotting and immunohistochemistry to more comprehensive approaches including mass spectrometry and reverse phase protein lysate arrays (RPPA). The purpose of this manuscript is to review the current protein markers that influence breast cancer prediction and prognosis and to focus on novel advances in proteomic classification of breast cancer.

  8. Immunohistochemical expression of insulin-like growth factor binding protein-3 in invasive breast cancers and ductal carcinoma in situ: implications for clinicopathology and patient outcome

    International Nuclear Information System (INIS)

    Insulin-like growth factor binding protein-3 (IGFBP-3) differentially modulates breast epithelial cell growth through insulin-like growth factor (IGF)-dependent and IGF-independent pathways and is a direct (IGF-independent) growth inhibitor as well as a mitogen that potentiates EGF (epidermal growth factor) and interacts with HER-2. Previously, high IGFBP-3 levels in breast cancers have been determined by enzyme-linked immunosorbent assay and immunoradiometric assay methods. In vitro, IGFBP-3's mechanisms of action may involve cell membrane binding and nuclear translocation. To evaluate tumour-specific IGFBP-3 expression and its subcellular localisation, this study examined immunohistochemical IGFBP-3 expression in a series of invasive ductal breast cancers (IDCs) with synchronous ductal carcinomas in situ (DCIS) in relation to clinicopathological variables and patient outcome. Immunohistochemical expression of IGFBP-3 was evaluated with the sheep polyclonal antiserum (developed in house) with staining performed as described previously. IGFBP-3 was evaluable in 101 patients with a variable pattern of cytoplasmic expression (positivity of 1+/2+ score) in 85% of invasive and 90% of DCIS components. Strong (2+) IGFBP-3 expression was evident in 32 IDCs and 40 cases of DCIS. A minority of invasive tumours (15%) and DCIS (10%) lacked IGFBP-3 expression. Nuclear IGFBP-3 expression was not detectable in either invasive cancers or DCIS, with a consistent similarity in IGFBP-3 immunoreactivity in IDCs and DCIS. Positive IGFBP-3 expression showed a possible trend in association with increased proliferation (P = 0.096), oestrogen receptor (ER) negativity (P = 0.06) and HER-2 overexpression (P = 0.065) in invasive tumours and a strong association with ER negativity (P = 0.037) in DCIS. Although IGFBP-3 expression was not an independent prognosticator, IGFBP-3-positive breast cancers may have shorter disease-free and overall survivals, although these did not reach

  9. Breast cancer risk factors.

    Science.gov (United States)

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

    2015-09-01

    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

  10. Breast cancer risk factors

    Directory of Open Access Journals (Sweden)

    Marzena Kamińska

    2015-09-01

    Full Text Available 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.

  11. Understanding breast cancer risk.

    Science.gov (United States)

    Anderson, Robin L

    2010-01-01

    With mammography firmly established as an integral part of efforts to reduce breast cancer mortality, many believe it is time to concentrate on prevention. Part of the multifaceted approach to preventing and treating this disease is unraveling its molecular, genetic and physiological makeup. Another aspect is ensuring that women have the information they need to make informed decisions about screening and treatment. Studies also point to the influence of nutrition, exercise, medicines and a patient's adherence to screening on cancer risk and recovery. PMID:20445140

  12. Interleukin-19 in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ying-Yin Chen

    2013-01-01

    Full Text Available Inflammatory cytokines within the tumor microenvironment are linked to progression in breast cancer. Interleukin- (IL- 19, part of the IL-10 family, contributes to a range of diseases and disorders, such as asthma, endotoxic shock, uremia, psoriasis, and rheumatoid arthritis. IL-19 is expressed in several types of tumor cells, especially in squamous cell carcinoma of the skin, tongue, esophagus, and lung and invasive duct carcinoma of the breast. In breast cancer, IL-19 expression is correlated with increased mitotic figures, advanced tumor stage, higher metastasis, and poor survival. The mechanisms of IL-19 in breast cancer have recently been explored both in vitro and in vivo. IL-19 has an autocrine effect in breast cancer cells. It directly promotes proliferation and migration and indirectly provides a microenvironment for tumor progression, which suggests that IL-19 is a prognostic marker in breast cancer and that antagonizing IL-19 may have therapeutic potential.

  13. Epidemiology of male breast cancer.

    Science.gov (United States)

    Weiss, Joli R; Moysich, Kirsten B; Swede, Helen

    2005-01-01

    Breast cancer in men is a rare disease, accounting for approximately 1% of all breast cancer cases. Although the epidemiologic literature regarding female breast cancer is extensive, relatively little is known about the etiology of male breast cancer (MBC). This review is intended to summarize the existing body of evidence on genetic and epidemiologic risk factors for breast cancer in men. Overall, the epidemiology of MBC presents similarities with the epidemiology of female breast cancer. Major genetic factors associated with an increased risk of breast cancer for men include BRCA2 mutations, which are believed to account for the majority of inherited breast cancer in men, Klinefelter syndrome, and a positive family history. Suspected genetic factors include AR gene mutations, CYP17 polymorphism, Cowden syndrome, and CHEK2. Epidemiologic risk factors for MBC include disorders relating to hormonal imbalances, such as obesity, testicular disorders (e.g., cryptorchidism, mumps orchitis, and orchiectomy), and radiation exposure. Suspected epidemiologic risk factors include prostate cancer,prostate cancer treatment, gynecomastia, occupational exposures (e.g., electromagnetic fields, polycyclic aromatic hydrocarbons, and high temperatures), dietary factors (e.g., meat intake and fruit and vegetable consumption), and alcohol intake. PMID:15668471

  14. Isoliquiritigenin induces growth inhibition and apoptosis through downregulating arachidonic acid metabolic network and the deactivation of PI3K/Akt in human breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ying; Zhao, Haixia [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Wang, Yuzhong [Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079 (China); Zheng, Hao; Yu, Wei; Chai, Hongyan [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Zhang, Jing [Animal Experimental Center of Wuhan University, Wuhan 430071 (China); Falck, John R. [Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390,USA (United States); Guo, Austin M. [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Department of Pharmacology, New York Medical College, Valhalla, NY 10595 (United States); Yue, Jiang; Peng, Renxiu [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Yang, Jing, E-mail: yangjingliu2013@163.com [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2013-10-01

    Arachidonic acid (AA)-derived eicosanoids and its downstream pathways have been demonstrated to play crucial roles in growth control of breast cancer. Here, we demonstrate that isoliquiritigenin, a flavonoid phytoestrogen from licorice, induces growth inhibition and apoptosis through downregulating multiple key enzymes in AA metabolic network and the deactivation of PI3K/Akt in human breast cancer. Isoliquiritigenin diminished cell viability, 5-bromo-2′-deoxyuridine (BrdU) incorporation, and clonogenic ability in both MCF-7 and MDA-MB-231cells, and induced apoptosis as evidenced by an analysis of cytoplasmic histone-associated DNA fragmentation, flow cytometry and hoechst staining. Furthermore, isoliquiritigenin inhibited mRNA expression of multiple forms of AA-metabolizing enzymes, including phospholipase A2 (PLA2), cyclooxygenases (COX)-2 and cytochrome P450 (CYP) 4A, and decreased secretion of their products, including prostaglandin E{sub 2} (PGE{sub 2}) and 20-hydroxyeicosatetraenoic acid (20-HETE), without affecting COX-1, 5-lipoxygenase (5-LOX), 5-lipoxygenase activating protein (FLAP), and leukotriene B{sub 4} (LTB{sub 4}). In addition, it downregulated the levels of phospho-PI3K, phospho-PDK (Ser{sup 241}), phospho-Akt (Thr{sup 308}), phospho-Bad (Ser{sup 136}), and Bcl-x{sub L} expression, thereby activating caspase cascades and eventually cleaving poly(ADP-ribose) polymerase (PARP). Conversely, the addition of exogenous eicosanoids, including PGE{sub 2}, LTB{sub 4} and a 20-HETE analog (WIT003), and caspase inhibitors, or overexpression of constitutively active Akt reversed isoliquiritigenin-induced apoptosis. Notably, isoliquiritigenin induced growth inhibition and apoptosis of MDA-MB-231 human breast cancer xenografts in nude mice, together with decreased intratumoral levels of eicosanoids and phospho-Akt (Thr{sup 308}). Collectively, these data suggest that isoliquiritigenin induces growth inhibition and apoptosis through downregulating AA metabolic

  15. Isoliquiritigenin induces growth inhibition and apoptosis through downregulating arachidonic acid metabolic network and the deactivation of PI3K/Akt in human breast cancer

    International Nuclear Information System (INIS)

    Arachidonic acid (AA)-derived eicosanoids and its downstream pathways have been demonstrated to play crucial roles in growth control of breast cancer. Here, we demonstrate that isoliquiritigenin, a flavonoid phytoestrogen from licorice, induces growth inhibition and apoptosis through downregulating multiple key enzymes in AA metabolic network and the deactivation of PI3K/Akt in human breast cancer. Isoliquiritigenin diminished cell viability, 5-bromo-2′-deoxyuridine (BrdU) incorporation, and clonogenic ability in both MCF-7 and MDA-MB-231cells, and induced apoptosis as evidenced by an analysis of cytoplasmic histone-associated DNA fragmentation, flow cytometry and hoechst staining. Furthermore, isoliquiritigenin inhibited mRNA expression of multiple forms of AA-metabolizing enzymes, including phospholipase A2 (PLA2), cyclooxygenases (COX)-2 and cytochrome P450 (CYP) 4A, and decreased secretion of their products, including prostaglandin E2 (PGE2) and 20-hydroxyeicosatetraenoic acid (20-HETE), without affecting COX-1, 5-lipoxygenase (5-LOX), 5-lipoxygenase activating protein (FLAP), and leukotriene B4 (LTB4). In addition, it downregulated the levels of phospho-PI3K, phospho-PDK (Ser241), phospho-Akt (Thr308), phospho-Bad (Ser136), and Bcl-xL expression, thereby activating caspase cascades and eventually cleaving poly(ADP-ribose) polymerase (PARP). Conversely, the addition of exogenous eicosanoids, including PGE2, LTB4 and a 20-HETE analog (WIT003), and caspase inhibitors, or overexpression of constitutively active Akt reversed isoliquiritigenin-induced apoptosis. Notably, isoliquiritigenin induced growth inhibition and apoptosis of MDA-MB-231 human breast cancer xenografts in nude mice, together with decreased intratumoral levels of eicosanoids and phospho-Akt (Thr308). Collectively, these data suggest that isoliquiritigenin induces growth inhibition and apoptosis through downregulating AA metabolic network and the deactivation of PI3K/Akt in human breast cancer

  16. Transforming growth factor-β1 regulates epithelial-mesenchymal transition in association with cancer stem-like cells in a breast cancer cell line.

    Science.gov (United States)

    Jia, Yongfeng; Wu, Di; Yun, Fen; Shi, Lin; Luo, Nianrong; Liu, Zhiyue; Shi, Yonghong; Sun, Qinnuan; Jiang, Lili; Wang, Shiqi; Du, Maolin

    2014-01-01

    Epithelial-mesenchymal transition (EMT) is associated with altered connection and junctions between cells and changes in abilities of invasion and migration. In this study, we investigated whether SK-BR-3 breast cancer cells induced to undergo EMT exhibit changes in morphological and invasion abilities after Transforming growth factor β1 (TGF-β1) treatment. Serum-deprived SK-BR-3 cells were treated with TGF-β1 (0, 10 ng/mL) for 24 h. The cells morphological changes were observed and imaged using inverted phase contrast microscope. Scratch experiment and invasion experiment were employed to detect changes of invasion ability, cell-flow experiment was used to assess cell cycle, immunohistochemistry technique was used to detect epithelial and mesenchymal markers after the crawling cells were fixed. Our research reveal that SK-BR-3 cells become larger and more messy, the elongated cells extend pseudopodia, the link of the cells became more loosely and cell gap widened after TGF-β1 treatment. SK-BR-3 cells showed faster growing and improved invasion abilities after TGF-β1 treatment, and reduced G1 phase cells proportion in the total number of cells after the conversion, in contrast the S phase cells accounted for the proportion of the total number of cells increased. These findings indicate that TGF-β1-induced EMT in breast cancer cells may be associated with major alterations in morphological and invasion abilities. PMID:24955155

  17. Lentivirus-Mediated Short-Hairpin RNA Targeting Protein Phosphatase 4 Regulatory Subunit 1 Inhibits Growth in Breast Cancer

    OpenAIRE

    Qi, Yuying; Hu, Tinghui; Li, Kai; Ye, Renqing; Ye, Zuodong

    2015-01-01

    Purpose Protein phosphatase 4 regulatory subunit 1 (PP4R1), as an interaction partner of the catalytic serine/threonine-protein phosphatase 4 catalytic subunit has been shown to involve in cellular processes and nuclear factor κB signaling. However, the functions of PP4R1 in human breast cancers remain unclear. This study is designed to explore the effect of PP4R1 knockdown on the biological characteristics of breast cancer cells. Methods A lentivirus-mediated short hairpin RNA (shRNA) was de...

  18. Cytosolic phospholipase A2 activation correlates with HER2 overexpression and mediates estrogen-dependent breast cancer cell growth.

    OpenAIRE

    Caiazza, Francesco; Harvey, Brian J; Thomas, Warren

    2010-01-01

    Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) catalyzes the hydrolysis of membrane glycerol-phospholipids to release arachidonic acid as the first step of the eicosanoid signaling pathway. This pathway contributes to proliferation in breast cancer, and numerous studies have demonstrated a crucial role of cyclooxygenase 2 and prostaglandin E(2) release in breast cancer progression. The role of cPLA(2)alpha activation is less clear, and we recently showed that 17beta-estradiol (E2) can rapid...

  19. Breast cancer therapies weighed

    International Nuclear Information System (INIS)

    Even as the National Institutes of Health came under fire last week for giving short shrift to women in the institute's basic and clinical research programs, the report of a recent NIH consensus conference points up the need for more research on how to treat early breast cancer. Although the experts were able to agree on the best surgical treatment for women with early breast cancer, they couldn't resolve the more controversial issue of whether the patients should subsequently receive systemic treatment - chemotherapy or hormone therapy - to prevent recurrence of their disease. The panel reaffirmed that the removal of the lump and nearby lymph nodes, followed by irradiation, is just as effective as a mastectomy. But then came the contentious question: should women with early breast cancer, especially those without detectable lymph node metastases, receive drug therapy to prevent recurrence of the disease? Currently, 70% of such cancers are successfully treated with surgery and radiation alone. For this reason, about 2 years ago, the National Cancer Institute issued a clinical alert saying that addition treatment with drugs or hormones is a credible therapeutic option worthy of careful attention for all early stage patients. This pronouncement engendered a storm of criticism. A consensus panel concluded that in cases where tumors are 1 centimeter or less in diameter and no lymph nodes are affected, the likelihood of recurrence is so small that the benefits of adjuvant therapy would be insignificant. But for the patients with larger tumors, the panel concluded that the decision is an individual one that depends on personal preferences and a variety of prognostic factors that can help to indicate whether a woman is at high risk of having a recurrence and should therefore have adjuvant therapy

  20. Enhanced NK cell adoptive antitumor effects against breast cancer in vitro via blockade of the transforming growth factor-β signaling pathway

    Directory of Open Access Journals (Sweden)

    Zhao Y

    2015-06-01

    Full Text Available Yue Zhao,1,* Jinyue Hu,2,* Rongguo Li,1 Jian Song,1 Yujuan Kang,1 Si Liu,1 Dongwei Zhang1 1Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 2Department of Breast and Thyroid Surgery, The Third Hospital of Zhengzhou, Zhengzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Natural killer (NK cells have great potential for improving cancer immunotherapy. Adoptive NK cell transfer, an adoptive immunotherapy, represents a promising nontoxic anticancer therapy. However, existing data indicate that tumor cells can effectively escape NK cell-mediated apoptosis through immunosuppressive effects in the tumor microenvironment, and the therapeutic activity of adoptive NK cell transfer is not as efficient as anticipated. Transforming growth factor-beta (TGF-β is a potent immunosuppressant. Genetic and epigenetic events that occur during mammary tumorigenesis circumvent the tumor-suppressing activity of TGF-β, thereby permitting late-stage breast cancer cells to acquire an invasive and metastatic phenotype in response to TGF-β. To block the TGF-β signaling pathway, NK cells were genetically modified with a dominant-negative TGF-β type II receptor by optimizing electroporation using the Amaxa Nucleofector system. These genetically modified NK cells were insensitive to TGF-β and resisted the suppressive effect of TGF-β on MCF-7 breast cancer cells in vitro. Our results demonstrate that blocking the TGF-β signaling pathway to modulate the tumor microenvironment can improve the antitumor activity of adoptive NK cells in vitro, thereby providing a new rationale for the treatment of breast cancer. Keywords: transforming growth factor-beta, natural killer cells, breast cancer, adoptive immunotherapy

  1. Phyto-oestrogens and breast cancer chemoprevention

    International Nuclear Information System (INIS)

    Phytoestrogens are polyphenol compounds of plant origin that exhibit a structural similarity to the mammalian steroid hormone 17β-oestradiol. In Asian nations the staple consumption of phyto-oestrogen-rich foodstuffs correlates with a reduced incidence of breast cancer. Human dietary intervention trials have noted a direct relationship between phyto-oestrogen ingestion and a favourable hormonal profile associated with decreased breast cancer risk. However, these studies failed to ascertain the precise effect of dietary phyto-oestrogens on the proliferation of mammary tissue. Epidemiological and rodent studies crucially suggest that breast cancer chemoprevention by dietary phyto-oestrogen compounds is dependent on ingestion before puberty, when the mammary gland is relatively immature. Phyto-oestrogen supplements are commercially marketed for use by postmenopausal women as natural and safe alternatives to hormone replacement therapy. Of current concern is the effect of phyto-oestrogen compounds on the growth of pre-existing breast tumours. Data are contradictory, with cell culture studies reporting both the oestrogenic stimulation of oestrogen receptor-positive breast cancer cell lines and the antagonism of tamoxifen activity at physiological phyto-oestrogen concentrations. Conversely, phyto-oestrogen ingestion by rodents is associated with the development of less aggressive breast tumours with reduced metastatic potential. Despite the present ambiguity, current data do suggest a potential benefit from use of phyto-oestrogens in breast cancer chemoprevention and therapy. These aspects are discussed

  2. Radiotherapy for recurrent breast cancer

    International Nuclear Information System (INIS)

    Clinico-radiobiological characteristics of radiotherapy for relapsed breast cancer were studied. Adequate choice of tissue mass to be exposed appeared much more important than any change in focal dose within 50-80 Gy, to achieve higher frequency of locoregional therapeutic effect. However, recurrent tumors more than 3 large lower radiosensitivity involving a sharp rise in the likelihood of dissemination. Radiotherapy for primary tumor did not affect the radiosensitivity of recurrent malignancies but slowed down the rate of its growth. Also, it might promote the dissemination acceleration

  3. Phosphorus Magnetic Resonance Spectroscopy in Breast Cancer

    NARCIS (Netherlands)

    van der Kemp, W.J.M.

    2014-01-01

    At present, the risk of a woman developing invasive breast cancer during her life is about 1 in 8. This makes breast cancer the most prevalent type of cancer in women worldwide. As the risk of dying from breast cancer for a woman is about 1 in 36, early breast cancer detection and effective treatmen

  4. Frequently increased epidermal growth factor receptor (EGFR) copy numbers and decreased BRCA1 mRNA expression in Japanese triple-negative breast cancers

    International Nuclear Information System (INIS)

    Triple-negative breast cancer (estrogen receptor-, progesterone receptor-, and HER2-negative) (TNBC) is a high risk breast cancer that lacks specific therapy targeting these proteins. We studied 969 consecutive Japanese patients diagnosed with invasive breast cancer from January 1981 to December 2003, and selected TNBCs based on the immunohistochemical data. Analyses of epidermal growth factor receptor (EGFR) gene mutations and amplification, and BRCA1 mRNA expression were performed on these samples using TaqMan PCR assays. The prognostic significance of TNBCs was also explored. Median follow-up was 8.3 years. A total of 110 (11.3%) patients had TNBCs in our series. Genotyping of the EGFR gene was performed to detect 14 known EGFR mutations, but none was identified. However, EGFR gene copy number was increased in 21% of TNBCs, while only 2% of ER- and PgR-positive, HER2-negative tumors showed slightly increased EGFR gene copy numbers. Thirty-one percent of TNBCs stained positive for EGFR protein by immunohistochemistry. BRCA1 mRNA expression was also decreased in TNBCs compared with controls. Triple negativity was significantly associated with grade 3 tumors, TP53 protein accumulation, and high Ki67 expression. TNBC patients had shorter disease-free survival than non-TNBC in node-negative breast cancers. TNBCs have an aggressive clinical course, and EGFR and BRCA1 might be candidate therapeutic targets in this disease

  5. Breast Tissue Composition and Susceptibility to Breast Cancer

    OpenAIRE

    Boyd, Norman F.; Lisa J Martin; Bronskill, Michael; Martin J. Yaffe; 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 associat...

  6. Drugs Approved for Breast Cancer

    Science.gov (United States)

    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.

  7. In vitro and in vivo inhibition of breast cancer cell growth by targeting the Hedgehog/GLI pathway with SMO (GDC-0449) or GLI (GANT-61) inhibitors

    Science.gov (United States)

    De Smaele, Enrico; Fantini, Massimo; Mattera, Rosanna; Cucchi, Danilo; Bonanno, Elena; Di Stefano, Enrica; Frajese, Giovanni Vanni; Orlandi, Augusto; Screpanti, Isabella; Gulino, Alberto; Modesti, Andrea; Bei, Roberto

    2016-01-01

    Aberrant Hedgehog (Hh)/glioma-associated oncogene (GLI) signaling has been implicated in cancer progression. Here, we analyzed GLI1, Sonic Hedgehog (Shh) and NF-κB expression in 51 breast cancer (ductal carcinoma) tissues using immunohistochemistry. We found a positive correlation between nuclear GLI1 expression and tumor grade in ductal carcinoma cases. Cytoplasmic Shh staining significantly correlated with a lower tumor grade. Next, the in vitro effects of two Hh signaling pathway inhibitors on breast cancer cell lines were evaluated using the Smoothened (SMO) antagonist GDC-0449 and the direct GLI1 inhibitor GANT-61. GDC-0449 and GANT-61 exhibited the following effects: a) inhibited breast cancer cell survival; b) induced apoptosis; c) inhibited Hh pathway activity by decreasing the mRNA expression levels of GLI1 and Ptch and inhibiting the nuclear translocation of GLI1; d) increased/decreased EGFR and ErbB2 protein expression, reduced p21-Ras and ERK1/ERK2 MAPK activities and inhibited AKT activation; and e) decreased the nuclear translocation of NF-κB. However, GANT-61 exerted these effects more effectively than GDC-0449. The in vivo antitumor activities of GDC-0449 and GANT-61 were analyzed in BALB/c mice that were subcutaneously inoculated with mouse breast cancer (TUBO) cells. GDC-0449 and GANT-61 suppressed tumor growth of TUBO cells in BALB/c mice to different extents. These findings suggest that targeting the Hh pathway using antagonists that act downstream of SMO is a more efficient strategy than using antagonists that act upstream of SMO for interrupting Hh signaling in breast cancer. PMID:26843616

  8. Pyruvate Carboxylase Is Up-Regulated in Breast Cancer and Essential to Support Growth and Invasion of MDA-MB-231 Cells.

    Directory of Open Access Journals (Sweden)

    Phatchariya Phannasil

    Full Text Available Pyruvate carboxylase (PC is an anaplerotic enzyme that catalyzes the carboxylation of pyruvate to oxaloacetate, which is crucial for replenishing tricarboxylic acid cycle intermediates when they are used for biosynthetic purposes. We examined the expression of PC by immunohistochemistry of paraffin-embedded breast tissue sections of 57 breast cancer patients with different stages of cancer progression. PC was expressed in the cancerous areas of breast tissue at higher levels than in the non-cancerous areas. We also found statistical association between the levels of PC expression and tumor size and tumor stage (P < 0.05. The involvement of PC with these two parameters was further studied in four breast cancer cell lines with different metastatic potentials; i.e., MCF-7, SKBR3 (low metastasis, MDA-MB-435 (moderate metastasis and MDA-MB-231 (high metastasis. The abundance of both PC mRNA and protein in MDA-MB-231 and MDA-MB-435 cells was 2-3-fold higher than that in MCF-7 and SKBR3 cells. siRNA-mediated knockdown of PC expression in MDA-MB-231 and MDA-MB-435 cells resulted in a 50% reduction of cell proliferation, migration and in vitro invasion ability, under both glutamine-dependent and glutamine-depleted conditions. Overexpression of PC in MCF-7 cells resulted in a 2-fold increase in their proliferation rate, migration and invasion abilities. Taken together the above results suggest that anaplerosis via PC is important for breast cancer cells to support their growth and motility.

  9. The role of versican G3 domain in regulating breast cancer cell motility including effects on osteoblast cell growth and differentiation in vitro – evaluation towards understanding breast cancer cell bone metastasis

    Directory of Open Access Journals (Sweden)

    Du William

    2012-08-01

    Full Text Available Abstract Background Versican is detected in the interstitial tissues at the invasive margins of breast carcinoma, is predictive of relapse, and negatively impacts overall survival rates. The versican G3 domain is important in breast cancer cell growth, migration and bone metastasis. However, mechanistic studies evaluating versican G3 enhanced breast cancer bone metastasis are limited. Methods A versican G3 construct was exogenously expressed in the 66c14 and the MC3T3-E1 cell line. Cells were observed through light microscopy and viability analyzed by Coulter Counter or determined with colorimetric proliferation assays. The Annexin V-FITC apoptosis detection kit was used to detect apoptotic activity. Modified Chemotactic Boyden chamber migration invasion assays were applied to observe tumor migration and invasion to bone stromal cells and MC3T3-E1 cells. Alkaline phosphatase (ALP staining and ALP ELISA assays were performed to observe ALP activity in MC3T3-E1 cells. Results In the four mouse breast cancer cell lines 67NR, 66c14, 4T07, and 4T1, 4T1 cells expressed higher levels of versican, and showed higher migration and invasion ability to MC3T3-E1 cells and primary bone stromal cells. 4T1 conditioned medium (CM inhibited MC3T3-E1 cell growth, and even lead to apoptosis. Only 4T1 CM prevented MC3T3-E1 cell differentiation, noted by inhibition of alkaline phosphatase (ALP activity. We exogenously expressed a versican G3 construct in a cell line that expresses low versican levels (66c14, and observed that the G3-expressing 66c14 cells showed enhanced cell migration and invasion to bone stromal and MC3T3-E1 cells. This observation was prevented by selective EGFR inhibitor AG1478, selective MEK inhibitor PD 98059, and selective AKT inhibitor Triciribine, but not by selective JNK inhibitor SP 600125. Versican G3 enhanced breast cancer cell invasion to bone stromal cells or osteoblast cells appears to occur through enhancing EGFR/ERK or AKT signaling

  10. Hwanggeumchal sorghum induces cell cycle arrest, and suppresses tumor growth and metastasis through Jak2/STAT pathways in breast cancer xenografts.

    Directory of Open Access Journals (Sweden)

    Jin Hee Park

    Full Text Available BACKGROUND: Cancer is one of the highly virulent diseases known to humankind with a high mortality rate. Breast cancer is the most common cancer in women worldwide. Sorghum is a principal cereal food in many parts of the world, and is critical in folk medicine of Asia and Africa. In the present study, we analyzed the effects of HSE in metastatic breast cancer. METHODOLOGY/PRINCIPAL FINDINGS: Preliminary studies conducted on MDA-MB 231 and MCF-7 xenograft models showed tumor growth suppression by HSE. Western blotting studies conducted both in vivo and in vitro to check the effect of HSE in Jak/STAT pathways. Anti-metastatic effects of HSE were confirmed using both MDA-MB 231 and MCF-7 metastatic animal models. These studies showed that HSE can modulate Jak/STAT pathways, and it hindered the STAT5b/IGF-1R and STAT3/VEGF pathways not only by down-regulating the expression of these signal molecules and but also by preventing their phosphorylation. The expression of angiogenic factors like VEGF, VEGF-R2 and cell cycle regulators like cyclin D, cyclin E, and pRb were found down-regulated by HSE. In addition, it also targets Brk, p53, and HIF-1α for anti-cancer effects. HSE induced G1 phase arrest and migration inhibition in MDA-MB 231 cells. The metastasis of breast cancer to the lungs also found blocked by HSE in the metastatic animal model. CONCLUSIONS/SIGNIFICANCE: Usage of HS as a dietary supplement is an inexpensive natural cancer therapy, without any side effects. We strongly recommend the use of HS as an edible therapeutic agent as it possesses tumor suppression, migration inhibition, and anti-metastatic effects on breast cancer.

  11. BREAST CANCER: IS OBESITY A RISK FACTOR?

    Directory of Open Access Journals (Sweden)

    Anjali

    2015-11-01

    Full Text Available Most epidemiological studies established obesity as an important risk factor for breast cancer. It is one of the few risk factors that women can modify. Now-a-days breast cancer is considered to be a life-style disease. The relation of obesity to breast cancer is complex one. Obesity is found to be associated with increased risk of cancer in post-menopausal women, but relation is reverse in pre-menopausal women. In these patients, obesity increases risk due to enhanced oestrogenic activity in obese females. Apart from it, other factors like Insulin-like Growth Factor (IGF-1, Leptin has also been involved. Due to big breasts in obese females there is delay in seeking medical attention, delay in diagnosis, poor response to surgery, chemotherapy, radiotherapy and associated complication during treatment. We study the effect of obesity (Weight, BMI, WHR as a risk factor in occurrence of breast cancer in local population of Southern part of Rajasthan in India. We found no significant association between obesity and increased risk of breast cancer in local population of this region where women are multiparous, physically active and usually do not use exogenous hormones.

  12. Computer model challenges breast cancer treatment strategy.

    Science.gov (United States)

    Retsky, M W; Swartzendruber, D E; Bame, P D; Wardwell, R H

    1994-01-01

    The breast cancer treatment failure rate remains unacceptably high. The current breast cancer treatment paradigm, based primarily on Gompertzian kinetics and animal models, advocates short-course, intensive chemotherapy subsequent to tumor debulking, citing drug resistance and host toxicity as the primary reasons for treatment failure. To better understand treatment failure, we have studied breast cancer from the perspective of computer modeling. Our results demonstrate breast cancers grow in an irregular fashion; this differs from the Gompertzian mode of animal models and thus challenges the validity of the current paradigm. Clinical and laboratory data support the concept of irregular growth rather than the common claim that human tumors grow in a Gompertzian fashion. Treatment failure mechanisms for breast cancer appear to differ from those for animal models, and thus treatments optimize on animal models may not be optimal for breast cancer. A failure mechanism consistent with our results involves temporarily dormant tumor cells in anatomical or pharmacological sanctuary, which eventually result in aggressive metastatic disease. PMID:7994590

  13. Effect of Sterols Isolated from Myrtillocactus geometrizans on Growth Inhibition of Colon and Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Mario Augusto Bolaños-Carrillo

    2015-01-01

    Full Text Available Objective. To explore the effect of peniocerol and macdougallin on HCT-15 and MCF-7 cells proliferation, cell cycle, apoptosis, and PARP cleavage. Methods. HCT-15 and MCF-7 cells were treated with various concentrations of peniocerol and macdougallin (10–80 μM during 24 or 48 h. Crystal Violet Assay was used to evaluate the inhibition effect. Cell cycle regulation was examined by a propidium iodide method. Cell apoptosis was detected through both Annexin–V FLUOS/PI double-labeled cytometry assays and Western blot was applied to assess PARP cleavage. Results. Peniocerol and macdougallin induced growth inhibition and apoptosis in vitro in a time- and dose-dependent manner. Moreover, peniocerol and macdougallin induced arrest of cell cycle-dependent manner and increased the proportion of cells in G0/G1 phase. PARP cleavage in HCT-15 and MCF-7 cells was induced by treatment with peniocerol and macdougallin after 36 hours. Conclusions. Our results showed that the mechanism of cytotoxicity displayed by peniocerol and macdougallin is related to cell cycle arrest and apoptosis in both cell lines. This is a significant observation because it helps to understand the way some oxysterols isolated from Myrtillocactus geometrizans develop their biological activities against cancer cells.

  14. Ovarian stimulation in patients with breast cancer.

    Science.gov (United States)

    Muñoz, Elkin; González, Naira; Muñoz, Luis; Aguilar, Jesús; Velasco, Juan A García

    2015-01-01

    Breast cancer is the most prevalent malignancy among women under 50. Improvements in diagnosis and treatment have yielded an important decrease in mortality in the last 20 years. In many cases, chemotherapy and radiotherapy develop side effects on the reproductive function. Therefore, before the anti-cancer treatment impairs fertility, clinicians should offer some techniques for fertility preservation for women planning motherhood in the future. In order to obtain more available oocytes for IVF, the ovary must be stimulated. New protocols which prevent exposure to increased estrogen during gonadotropin stimulation, measurements to avoid the delay in starting anti-cancer treatment or the outcome of ovarian stimulation have been addressed in this review. There is no evidence of association between ovarian stimulation and breast cancer. It seems that there are more relevant other confluent factors than ovarian stimulation. Factors that can modify the risk of breast cancer include: parity, age at full-term birth, age of menarche, and family history. There is an association between breast cancer and exogenous estrogen. Therefore, specific protocols to stimulate patients with breast cancer include anti-estrogen agents such as letrozole. By using letrozole plus recombinant follicular stimulating hormone, patients develop a multifollicular growth with only a mild increase in estradiol serum levels. Controlled ovarian stimulation (COS) takes around 10 days, and we discuss new strategies to start COS as soon as possible. Protocols starting during the luteal phase or after inducing the menses currently prevent a delay in starting ovarian stimulation. Patients with breast cancer have a poorer response to COS compared with patients without cancer who are stimulated with conventional protocols of gonadotropins. Although many centres offer fertility preservation and many patients undergo ovarian stimulation, there are not enough studies to evaluate the recurrence, breast cancer

  15. Inhibition of insulin- and insulin-like growth factor-I-stimulated growth of human breast cancer cells by 1,25-dihydroxyvitamin D3 and the vitamin D3 analogue EB1089

    NARCIS (Netherlands)

    T. Vink-Van Wijngaarden (Trudy); H.A.P. Pols (Huib); C.J. Buurman (Cok); J.C. Birkenhäger (Jan ); J.P.T.M. van Leeuwen (Hans)

    1996-01-01

    textabstract1, 25 Dihydroxyvitamin D3 (1,25-(OH)2D3) and a number of synthetic vitamin D3 analogues with low calcaemic activity, have been shown to inhibit breast cancer cell growth in vitro as well as in vivo. The purpose of the present study was to investigate a possible interaction of 1, 25-(OH)2

  16. Conjugated Linoleic Acid (CLA) inhibits expression of the Spot 14 (THRSP) and fatty acid synthase genes and impairs the growth of human breast cancer and liposarcoma cells

    OpenAIRE

    Donnelly, Christina; Olsen, Arne M.; Lewis, Lionel D; Eisenberg, Burton L.; Eastman, Alan; Kinlaw, William B

    2009-01-01

    Spot 14 (THRSP, S14) is a nuclear protein involved in the regulation of genes required for fatty acid synthesis in normal and malignant mammary epithelial and adipose cells. Havartine and Bauman reported that conjugated linoleic acid (CLA) inhibits S14 gene expression in bovine mammary and mouse adipose tissues, and reduces milk fat production in cows. We hypothesized that CLA inhibits S14 gene expression in human breast cancer and liposarcoma cells, and that this will retard their growth. Ex...

  17. Biological markers of invasive breast cancer.

    Science.gov (United States)

    Matsumoto, Akiko; Jinno, Hiromitsu; Ando, Tomofumi; Fujii, Taku; Nakamura, Tetsuya; Saito, Junichi; Takahashi, Maiko; Hayashida, Tetsu; Kitagawa, Yuko

    2016-02-01

    Biological markers for breast cancer are biomolecules that result from cancer-related processes and are associated with particular clinical outcomes; they thus help predict responses to therapy. In recent years, gene expression profiling has made the molecular classification of breast cancer possible. Classification of breast cancer by immunohistochemical expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 and Ki-67 is standard practice for clinical decision-making. Assessments of hormone receptor expression and human epidermal growth factor receptor 2 overexpression help estimate benefits from targeted therapies and have greatly improved prognoses for women with these breast cancer types. Although Ki-67 positivity is associated with an adverse outcome, its clear identification is an aid to optimal disease management. Standardization of testing methodology to minimize inter-laboratory measurement variations is a remaining issue. Multi-gene assays provide prognostic information and identify those most likely to benefit from systemic chemotherapy. Incorporating molecular profiles with conventional pathological classification would be more precise, and could enhance the clinical development of personalized therapy in breast cancer. PMID:26486826

  18. The cancer growth suppressor gene mda-7 selectively induces apoptosis in human breast cancer cells and inhibits tumor growth in nude mice

    OpenAIRE

    Su, Zao-Zhong; Madireddi, Malavi T.; Lin, Jiao Jiao; Young, Charles S. H.; Kitada, Shinichi; Reed, John C.; Goldstein, Neil I.; Fisher, Paul B.

    1998-01-01

    A differentiation induction subtraction hybridization strategy is being used to identify and clone genes involved in growth control and terminal differentiation in human cancer cells. This scheme identified melanoma differentiation associated gene-7 (mda-7), whose expression is up-regulated as a consequence of terminal differentiation in human melanoma cells. Forced expression of mda-7 is growth inhibitory toward diverse human tumor cells. The present studies elucidate the mechanism by which ...

  19. Modulation of Δ9-tetrahydrocannabinol-induced MCF-7 breast cancer cell growth by cyclooxygenase and aromatase

    International Nuclear Information System (INIS)

    Δ9-Tetrahydrocannabinol (Δ9-THC), a major constituent of marijuana, has been shown to stimulate the growth of MCF-7 breast cancer cells through cannabinoid receptor-independent signaling [Takeda, S., Yamaori, S., Motoya, E., Matsunaga, T., Kimura, T., Yamamoto, I., Watanabe, K., 2008. Δ9-Tetrahydrocannabinol enhances MCF-7 cell proliferation via cannabinoid receptor-independent signaling. Toxicology 245, 141-146]. Although the growth of MCF-7 cells is known to be stimulated by 17β-estradiol (E2), the interaction of Δ9-THC and E2 in MCF-7 cell growth is not fully clarified so far. In the present study, by using E2-sensitive MCF-7 cells that have expressed cyclooxygenase-2 (COX-2) and cytochrome P450 19 (aromatase), we studied whether or not COX-2 and aromatase are involved in Δ9-THC-mediated MCF-7 cell proliferation. It was shown that Δ9-THC-induced MCF-7 cell growth was inhibited by COX-2 inhibitors and was stimulated by arachidonic acid (a COX substrate). However, the growth of MCF-7 cells induced by Δ9-THC was not stimulated by PGE2, and the expression of aromatase was not affected by COX-2 inhibitors, arachidonic acid, and PGE2, suggesting that there is a disconnection between COX-2 (PGE2) and aromatase in Δ9-THC-mediated MCF-7 cell proliferation. On the other hand, Δ9-THC-induced MCF-7 cell growth was elevated by two kinds of aromatase inhibitors. Taken together with the evidence that Δ9-THC-induced MCF-7 cell proliferation was interfered with testosterone (an aromatase substrate) and exogenously provided E2, it is suggested that (1) the growth stimulatory effects of Δ9-THC are mediated by the product(s) of COX-2 except for PGE2, (2) the action of Δ9-THC is modulated by E2, and (3) COX-2 and aromatase are individually engaged in the proliferation of MCF-7 cells induced by Δ9-THC.

  20. Breast and Colon Cancer Family Registries

    Science.gov (United States)

    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.

  1. Reproduction and Breast Cancer Risk

    OpenAIRE

    Hanf, Volker; Hanf, Dorothea

    2014-01-01

    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 w...

  2. Inhibition of insulin- and insulin-like growth factor-I-stimulated growth of human breast cancer cells by 1,25-dihydroxyvitamin D3 and the vitamin D3 analogue EB1089

    OpenAIRE

    Vink-Van Wijngaarden, Trudy; Pols, Huib; Buurman, Cok; Birkenhäger, Jan; van Leeuwen, Hans

    1996-01-01

    textabstract1, 25 Dihydroxyvitamin D3 (1,25-(OH)2D3) and a number of synthetic vitamin D3 analogues with low calcaemic activity, have been shown to inhibit breast cancer cell growth in vitro as well as in vivo. The purpose of the present study was to investigate a possible interaction of 1, 25-(OH)2D3 and the vitamin D3 analogue EB1089 with the insulin-IGF-I regulatory system. The oestrogen receptor-positive MCF-7 human breast cancer cells used in this study are able to grow autonomously and ...

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

    Science.gov (United States)

    2016-02-09

    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. Stearidonic acid-enriched flax oil reduces the growth of human breast cancer in vitro and in vivo.

    Science.gov (United States)

    Subedi, K; Yu, H-M; Newell, M; Weselake, R J; Meesapyodsuk, D; Qiu, X; Shah, S; Field, C J

    2015-01-01

    The 20 and 22 carbon n-3 long-chain polyunsaturated fatty acids (LCPUFA) inhibit the growth of tumors in vitro and in animal models, but less is known about the 18 carbon n-3, stearidonic acid (SDA). This study aimed to establish and determine a mechanism for the anti-cancer activity of SDA-enriched oil (SO). SO (26 % of lipid) was produced by genetically engineering flax and used to treat human tumorigenic (MDA-MB-231, MCF-7) and non-tumorigenic (MCF-12A) breast cells. Nu/nu mice bearing MDA-MB-231 tumor were fed SO (SDA, 4 % of fat). Cell/tumor growth, phospholipid (PL) composition, apoptosis, CD95, and pro-apoptotic molecules were determined in SO-treated cells/tumors. Compared to a control lipid mixture, SO reduced (p < 0.05) the number of tumorigenic, but not MCF-12A cells, and resulted in higher concentration of most of the n-3 fatty acids in PL of all cells (p < 0.05). However, docosapentaenoic acid increased only in tumorigenic cells (p < 0.05). SO diet decreased tumor growth and resulted in more n-3 LCPUFA, including DPA and less arachidonic acid (AA) levels in major tumor PL (p < 0.05). Treatment of MDA-MB-231 cells/tumors with SO resulted in more apoptotic cells (in tumors) and in vivo and in vitro, more CD95+ positive cells and a higher expression of apoptotic molecules caspase-10, Bad, or Bid (p < 0.05). Supplementing SO alters total PL and PL classes by increasing membrane content of n-3 LCPUFA and lowering AA (in vivo), which is associated with increased CD95-mediated apoptosis, thereby suggesting a possible mechanism for reduce tumor survival. PMID:25417173

  5. Breast cancers in elderly women

    International Nuclear Information System (INIS)

    Breast cancer is the most commonly diagnosed cancer and leading cause of cancer mortality in women worldwide. Nearly half of the global total of breast cancer cases occurs in patients > 65 years of age. Advanced age at the diagnosis of breast cancer is associated with more favorable tumor biology, as indicated by increased hormone sensitivity, attenuated HER- 2/neu overexpression, and lower grades and proliferative indices Elderly patients, however, are more likely to present with larger and more advanced tumors, and recent reports suggest that lymph node involvement increases with age. Elderly patients care less likely to be treated according to accepted treatment guidelines and under treatment can, as a consequence, have a strong negative impact on survival.Breast cancer in elderly patients represents a great social problem and is expected to remain one of the most common cancers in the next half century. (author)

  6. Leptin: A proliferative factor for breast cancer?

    International Nuclear Information System (INIS)

    Mammary adipose tissue is an important source of paracrine mitogens and anti-mitogens, including insulin-like growth factor, transforming growth factors, and cytokines (especially, TNFα and IL-1β). Nevertheless, it is also an important source of the adipocytokine, leptin. Recently, leptin was reported to stimulate the proliferation of various cell types (pancreatic β cells, prostate, colorectal, lung, etc.) as a new growth factor. It was also shown to stimulate the proliferation of breast cancer cell lines. In this study, we conducted an immunohistochemical analysis of leptin expression in normal tissue and benign and malignant ductal breast cell, representing the different states of the invasion process. We determined for the first time that leptin is expressed both by ductal breast tumors and by benign lesions as atypical hyperplasia. This suggests that leptin may be taken up or synthesized by all modified ductal breast cells, and may prove a proliferative factor. Moreover, leptin is unexpressed by normal tissue in the healthy breast but is exhibited by the normal tissue in near vicinity of the malignant ductal breast lesions. We also postulated that leptin may be a prognostic or diagnostic factor for ductal breast cancer. These putative hypotheses require further study

  7. Decline in breast cancer mortality

    DEFF Research Database (Denmark)

    Njor, Sisse Helle; Schwartz, Walter; Blichert-Toft, Mogens;

    2015-01-01

    OBJECTIVES: When estimating the decline in breast cancer mortality attributable to screening, the challenge is to provide valid comparison groups and to distinguish the screening effect from other effects. In Funen, Denmark, multidisciplinary breast cancer management teams started before screening...... was introduced; both activities came later in the rest of Denmark. Because Denmark had national protocols for breast cancer treatment, but hardly any opportunistic screening, Funen formed a "natural experiment", providing valid comparison groups and enabling the separation of the effect of screening...... from other factors. METHODS: Using Poisson regression we compared the observed breast cancer mortality rate in Funen after implementation of screening with the expected rate without screening. The latter was estimated from breast cancer mortality in the rest of Denmark controlled for historical...

  8. Statins and breast cancer prognosis

    DEFF Research Database (Denmark)

    Ahern, Thomas P; Lash, Timothy L; Damkier, Per;

    2014-01-01

    Much preclinical and epidemiological evidence supports the anticancer effects of statins. Epidemiological evidence does not suggest an association between statin use and reduced incidence of breast cancer, but does support a protective effect of statins-especially simvastatin-on breast cancer...... recurrence. Here, we argue that the existing evidence base is sufficient to justify a clinical trial of breast cancer adjuvant therapy with statins and we advocate for such a trial to be initiated without delay. If a protective effect of statins on breast cancer recurrence is supported by trial evidence......, then the indications for a safe, well tolerated, and inexpensive treatment can be expanded to improve outcomes for breast cancer survivors. We discuss several trial design opportunities-including candidate predictive biomarkers of statin safety and efficacy-and off er solutions to the key challenges...

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

    Science.gov (United States)

    2015-09-09

    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

  10. Breast cancer stem cells: implications for therapy of breast cancer

    OpenAIRE

    Morrison, Brian J.; Schmidt, Chris W.; Lakhani, Sunil R; Reynolds, Brent A.; Lopez, J. Alejandro

    2008-01-01

    The concept of cancer stem cells responsible for tumour origin, maintenance, and resistance to treatment has gained prominence in the field of breast cancer research. The therapeutic targeting of these cells has the potential to eliminate residual disease and may become an important component of a multimodality treatment. Recent improvements in immunotherapy targeting of tumour-associated antigens have advanced the prospect of targeting breast cancer stem cells, an approach that might lead to...

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

    OpenAIRE

    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...

  12. WNT signaling enhances breast cancer cell motility and blockade of the WNT pathway by sFRP1 suppresses MDA-MB-231 xenograft growth

    OpenAIRE

    Matsuda, Yutaka; Schlange, Thomas; Oakeley, Edward J.; Boulay, Anne; Nancy E Hynes

    2009-01-01

    Introduction In breast cancer, deregulation of the WNT signaling pathway occurs by autocrine mechanisms. WNT ligands and Frizzled receptors are coexpressed in primary breast tumors and cancer cell lines. Moreover, many breast tumors show hypermethylation of the secreted Frizzled-related protein 1 (sFRP1) promoter region, causing low expression of this WNT antagonist. We have previously shown that the WNT pathway influences proliferation of breast cancer cell lines via activation of canonical ...

  13. Molecular decoy to the Y-box binding protein-1 suppresses the growth of breast and prostate cancer cells whilst sparing normal cell viability.

    Directory of Open Access Journals (Sweden)

    Jennifer H Law

    Full Text Available The Y-box binding protein-1 (YB-1 is an oncogenic transcription/translation factor that is activated by phosphorylation at S102 whereby it induces the expression of growth promoting genes such as EGFR and HER-2. We recently illustrated by an in vitro kinase assay that a novel peptide to YB-1 was highly phosphorylated by the serine/threonine p90 S6 kinases RSK-1 and RSK-2, and to a lesser degree PKCα and AKT. Herein, we sought to develop this decoy cell permeable peptide (CPP as a cancer therapeutic. This 9-mer was designed as an interference peptide that would prevent endogenous YB-1(S102 phosphorylation based on molecular docking. In cancer cells, the CPP blocked P-YB-1(S102 and down-regulated both HER-2 and EGFR transcript level and protein expression. Further, the CPP prevented YB-1 from binding to the EGFR promoter in a gel shift assay. Notably, the growth of breast (SUM149, MDA-MB-453, AU565 and prostate (PC3, LNCap cancer cells was inhibited by ∼90% with the CPP. Further, treatment with this peptide enhanced sensitivity and overcame resistance to trastuzumab in cells expressing amplified HER-2. By contrast, the CPP had no inhibitory effect on the growth of normal immortalized breast epithelial (184htert cells, primary breast epithelial cells, nor did it inhibit differentiation of hematopoietic progenitors. These data collectively suggest that the CPP is a novel approach to suppressing the growth of cancer cells while sparing normal cells and thereby establishes a proof-of-concept that blocking YB-1 activation is a new course of cancer therapeutics.

  14. Mitochondrial Defects in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Josefa Salgado

    2008-01-01

    Full Text Available Mitochondria play important roles in cellular energy metabolism, free radical generation, and apoptosis. Mitochondrial DNA has been proposed to be involved in carcinogenesis because of its high susceptibility to mutations and limited repair mechanisms in comparison to nuclear DNA. Breast cancer is the most frequent cancer type among women in the world and, although exhaustive research has been done on nuclear DNA changes, several studies describe a variety of mitochondrial DNA alterations present in breast cancer. In this review article, we to provide a summary of the mitochondrial genomic alterations reported in breast cancer and their functional consequences.

  15. Unemployment among breast cancer survivors

    DEFF Research Database (Denmark)

    Carlsen, Kathrine; Ewertz, Marianne; Dalton, Susanne Oksbjerg;

    2014-01-01

    cancer. METHOD: 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......AIM: 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...

  16. The combined status of estrogen receptor (ER) and epidermal growth factor (EGFR) predicts a poor outcome in primary breast cancer

    International Nuclear Information System (INIS)

    The aim of this study was to investigate retrospectively the presence of ER, PR, Db Receptor and Epidermal Growth Factor (EGFR) in 678 patients carrying primary breast cancer, its correlation with clinic pathological parameters and evolution. the determination of ER, PR and EGFR was performed by Scatchard biochemical technique, based cutoff 10 fmoles / mg of protein. The RE-b detection performed by RT-PCR from total RNA, using the GAPDH gene as a control. Statistical analyzes were applied the Chi2 tests, Spearman and Kruskal-Wallis. The disease-free survival (SVLE) and survival overall (SVG) were analyzed using Kaplan Meier / Log Rank Test and analysis Cox regression. Median follow-up was 28 months (range 1-218 months). sixty Four percent of the patients were post-menopausal and 83% occurred in stages Early disease (I-II, pTNM UICC). The receptor positivity was 68%, 47%, 23% and 58% for ER, PR, EGFR and ER-b-mRNA, respectively. A correlation was found positive between the content of ER and PR (p = 1.10-5) and negative between these receptors and EGFR (n = 359, p = 0.014 and p = 0.018, respectively). We observed a trend to increased expression ER-b when ER, PR or both receptors were negative comparable to that observed with EGFR. Also, a gradual decrease in the content of ER and PR was observed with the progression to more advanced stages (p = 0.04 and p = 0.03). Of a total of 501 evaluable patients 23% relapsed and 12% died. ER positivity was associated with a greater SVLE and SVG 24 and 60 months follow up (p = 0.06). A major impact did the RE content, levels less than 45 fmol / mg protein were associated with disease recurrence (p = 0.03 and p = 0.006 for 24 and 60 months). Although less significant EGFR status influenced SVLE and SVG. In particular, the presence of EGFR in ER + group affected the evolution tripling relapses and deaths (p = 0.058). The presence of ER-b also had a negative impact on this patient group. In Cox regression analysis, N + and T> 2cm

  17. Vascular endothelial growth factor polymorphisms and clinical outcome in patients with metastatic breast cancer treated with weekly docetaxel.

    Science.gov (United States)

    Koutras, A K; Kotoula, V; Papadimitriou, C; Dionysopoulos, D; Zagouri, F; Kalofonos, H P; Kourea, H P; Skarlos, D V; Samantas, E; Papadopoulou, K; Kosmidis, P; Pectasides, D; Fountzilas, G

    2014-06-01

    The aim of the study was to evaluate the association of vascular endothelial growth factor (VEGF) genotypes with treatment efficacy in a phase II trial. This study evaluated weekly docetaxel, as first-line treatment for metastatic breast cancer. Existing data from in vitro and animal model experiments suggest that docetaxel at low doses has anti-angiogenic activity. DNA was extracted from blood samples of 86 patients participating in the trial. Genotyping was performed for selected single-nucleotide polymorphisms (SNPs; VEGF-2578, -1498, -1154, and +936). Moreover, due to the highly polymorphic nature of the studied areas, we were able to analyze additional registered SNPs. All candidate genotypes were evaluated for associations with overall survival (OS), progression-free survival (PFS) and response rate. The VEGF-1154 GG genotype was more frequent in patients not responding to treatment compared with responders (42.9% vs 0.0%, P=0.048). Moreover, the VEGF-2578 AA genotype was associated with longer PFS compared with CC (hazard ratio (HR)=0.40; 95% confidence interval (CI) 0.17-0.98; pairwise P=0.0457). Patients with the VEGF-1190 GG genotype demonstrated shorter PFS compared with those with the alternative genotypes (GA and AA) combined (HR=3.85; 95% CI: 1.20-12.50; P=0.0224). In addition, the VEGF-2551/-2534 homozygous del18bp and VEGF-2430/-2425 homozygous ins1bp genotypes were associated with worse PFS compared with no deletion and no insertion, respectively (HR=2.49; 95% CI: 1.02-6.07; pairwise P=0.0442 and HR=2.57; 95% CI: 1.05-6.27; pairwise P=0.0385, respectively). Furthermore, patients with the VEGF-1498 CC genotype exhibited longer median OS compared with those with the alternatives genotypes (CT and TT) combined (HR=0.27; 95% CI: 0.08-0.89; P=0.0311). In multivariate analysis, the VEGF-2578 AA genotype retained its significance (P=0.0220) for PFS. Our results support the association of specific VEGF genotypes with clinical outcome in patients with

  18. Effect of the knockdown of death-associated protein 1 expression on cell adhesion, growth and migration in breast cancer cells.

    Science.gov (United States)

    Wazir, Umar; Sanders, Andrew J; Wazir, Ali; Baig, Ruqia Mehmood; Jiang, Wen G; Ster, Irina C; Sharma, Anup K; Mokbel, Kefah

    2015-03-01

    Death-associated protein 1 (DAP1) is a highly conserved phosphoprotein involved in the regulation of autophagy. A previous clinical study by our group suggested an association between low DAP1 expression and clinicopathological parameters of human breast cancer. In the present study, we aimed to determine the role of DAP1 in cancer cell behaviour in the context of human breast cancer. We developed knockdown sublines of MCF7 and MDA-MB‑231, and performed growth, adhesion and invasion assays and electric cell-substrate impedance sensing (ECIS) studies of the post-wound migration of cells. In addition, we studied the mRNA expression of caspase 8 and 9, DELE, IPS1, cyclin D1 and p21 in the control and knockdown sublines. Knockdown was associated with increased adhesion and migration, significantly so in the MDA-MB-231DAP1kd cell subline (p=0.029 and p=0.001, respectively). Growth in MCF7 cells showed a significant suppression on day 3 (p=0.029), followed by an increase in growth matching the controls on day 5. While no change in the apoptotic response to serum starvation could be attributed to DAP1 knockdown, the expression of known components of the apoptosis pathway (caspase 8) and cell cycle (p21) was significantly reduced in the MCF7DAP1kd cell subline (p≤0.05), while in MDA-MB-231DAP1kd the expression of a pro-apoptotic molecule, IPS1, was suppressed (p≤0.05). DAP1 may have an important role in cell adhesion, migration and growth in the context of breast cancer and has significant associations with the apoptosis pathway. Furthermore, we believe that delayed increase in growth observed in the MCF7DAP1kd cell subline may indicate activation of a strongly pro-oncogenic pathway downstream of DAP1. PMID:25530065

  19. The T61 human breast cancer xenograft: an experimental model of estrogen therapy of breast cancer

    DEFF Research Database (Denmark)

    Brunner, N; Spang-Thomsen, M; Cullen, K

    1996-01-01

    Endocrine therapy is one of the principal treatment modalities of breast cancer, both in an adjuvant setting and in advanced disease. The T61 breast cancer xenograft described here provides an experimental model of the effects of estrogen treatment at a molecular level. T61 is an estrogen receptor...... in the study of the molecular mechanism of estrogen therapy in breast cancer, and suggest that in this system, modulation of a specific growth factor (IGF-II) by endocrine therapy can have profound effects on tumor growth....... positive tumor which was originally derived from a T1N0M0 invasive ductal cancer and has been carried as a serially transplanted xenograft in nude mice. T61 is a hormone sensitive tumor whose growth is suppressed by both estrogen and tamoxifen, in contrast to other estrogen receptor positive tumors such as...

  20. Enrichment of breast cancer stem-like cells by growth on electrospun polycaprolactone-chitosan nanofiber scaffolds

    Directory of Open Access Journals (Sweden)

    Sims-Mourtada J

    2014-02-01

    Full Text Available Jennifer Sims-Mourtada,1 Rohina A Niamat,2 Shani Samuel,2 Chris Eskridge,2 Eric B Kmiec1,2 1Center for Translational Cancer Research, Helen F Graham Cancer Center and Research Institute, Christiana Care Health Services, Inc, Newark, 2Department of Chemistry, Delaware State University, Dover, DE, USA Abstract: A small population of highly tumorigenic breast cancer cells has recently been identified. These cells, known as breast-cancer stem-like cells (BCSC, express markers similar to mammary stem cells, and are highly resistant to chemotherapy. Currently, study of BCSC is hampered by the inability to propagate these cells in tissue culture without inducing differentiation. Recently, it was reported that proliferation and differentiation can be modified by culturing cells on electrospun nanofibers. Here, we sought to characterize the chemoresistance and stem-like properties of breast cancer cell lines grown on nanofiber scaffolds. Cells cultured on three-dimensional templates of electrospun poly(ε-caprolactone-chitosan nanofibers showed increases in mammary stem cell markers and in sphere-forming ability compared with cells cultured on polystyrene culture dishes. There was no increase in proliferation of stem cell populations, indicating that culture on nanofibers may inhibit differentiation of BCSC. The increase in stemness was accompanied by increases in resistance to docetaxel and doxorubicin. These data indicate that BCSC populations are enriched in cells cultured on electrospun poly(ε-caprolactone-chitosan nanofibers, scaffolds that may provide a useful system to study BCSC and their response to anticancer drug treatment. Keywords: breast cancer, mammary stem cells, chemoresistance, nanofibers, three-dimensional culture

  1. Breast cancer in Kumasi, Ghana

    International Nuclear Information System (INIS)

    Breast cancer is the leading cause of cancer deaths in Ghanaian women.To describes the characteristics of breast cancer patients attending the Komfo Anokye Teaching Hospital in Kumasi, Ghana.The study was conducted at the Komfo Anokye Teaching Hospital. Between July 1st 2004 and June 30th 2009 patients presenting with breast lumps were assessed by clinical examination, imaging studies and pathological examination. Relevant clinical and pathological were recorded prospectively data on all patients with microscopically proven breast cancer. The cancers were graded according to the modified Bloom-Richardson system. Tissue immunoperoxidase stains for oestrogen, progesterone receptors and c-erb2 oncogene were performed with commercially prepared antigens and reagents.Nineteen thousand four hundred and twenty – three (19,423) patients were seen during the study period. There were 330 (1.7%) patients with histologically proven breast cancer. The mean age was 49.1 years. A palpable breast lump was detected in 248 patients (75.2%). Two hundred and eighty –one patients (85.2%) presented with Stages III and IV , 271 (82.1%) invasive and 230 ( 85.2%) high grade carcinomas. Oestrogen and progesterone receptors were positive in 32 and 9 cases respectively. Her2 protein was positive in 11 cases. In Kumasi, as in other parts of Ghana, breast cancer affects mostly young pre-menopausal who present with advanced disease. The cancers have unfavourable prognostic features and are unlikely to respond to hormonal therapy. (au)

  2. Aluminium, antiperspirants and breast cancer.

    Science.gov (United States)

    Darbre, P D

    2005-09-01

    Aluminium salts are used as the active antiperspirant agent in underarm cosmetics, but the effects of widespread, long term and increasing use remain unknown, especially in relation to the breast, which is a local area of application. Clinical studies showing a disproportionately high incidence of breast cancer in the upper outer quadrant of the breast together with reports of genomic instability in outer quadrants of the breast provide supporting evidence for a role for locally applied cosmetic chemicals in the development of breast cancer. Aluminium is known to have a genotoxic profile, capable of causing both DNA alterations and epigenetic effects, and this would be consistent with a potential role in breast cancer if such effects occurred in breast cells. Oestrogen is a well established influence in breast cancer and its action, dependent on intracellular receptors which function as ligand-activated zinc finger transcription factors, suggests one possible point of interference from aluminium. Results reported here demonstrate that aluminium in the form of aluminium chloride or aluminium chlorhydrate can interfere with the function of oestrogen receptors of MCF7 human breast cancer cells both in terms of ligand binding and in terms of oestrogen-regulated reporter gene expression. This adds aluminium to the increasing list of metals capable of interfering with oestrogen action and termed metalloestrogens. Further studies are now needed to identify the molecular basis of this action, the longer term effects of aluminium exposure and whether aluminium can cause aberrations to other signalling pathways in breast cells. Given the wide exposure of the human population to antiperspirants, it will be important to establish dermal absorption in the local area of the breast and whether long term low level absorption could play a role in the increasing incidence of breast cancer. PMID:16045991

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

    Science.gov (United States)

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

  4. Diet and breast cancer

    Directory of Open Access Journals (Sweden)

    Isabelle Romieu

    2011-10-01

    Full Text Available Both diet and nutrition have been studied in relationship with breast cancer risk, as the great variation among different countries in breast cancer incidence could possibly be explained through the inflammatory and immune response, as well as antioxidant intake, among others.To date, no clear association with diet beyond overweight and weight gain has been found, except for alcohol consumption. Nonetheless, the small number of studies done in middle to low income countries where variability of food intake is wider,is beginning to show interesting results.Tanto la dieta como la nutrición han sido estudiadas en relación con el riesgo de cáncer de mama, dada la gran variación de incidencia de cáncer entre países, y la posibilidad de explicarla a través de la respuesta inflamatoria o inmune, así como ingesta de antioxidantes,entre otros.Hasta la fecha, ninguna asociación clara con la dieta ha sido encontrada, excepto para el consumo de alcohol, más allá del sobrepeso y del incremento de peso. Sin embargo, los estudios que se están realizando en países de mediano a bajo nivel de ingresos, con mayor variabilidad de ingesta de alimentos, comienzan a mostrar resultados interesantes.

  5. Male breast cancer: is the scenario changing

    OpenAIRE

    Kulkarni Dhananjay M; Rodrigues Gabriel S; Kaur Kanchan; Contractor Kaiyumars B; Singhal Hemant

    2008-01-01

    Abstract Background The overall incidence of male breast cancer is around 1% of all breast cancers and is on the rise. In this review we aim to present various aspects of male breast cancer with particular emphasis on incidence, risk factors, patho-physiology, treatment, prognostic factors, and outcome. Methods Information on all aspects of male breast cancer was gathered from available relevant literature on male breast cancer from the MEDLINE database over the past 32 years from 1975 to 200...

  6. Intact and total insulin-like growth factor-binding protein-3 (IGFBP-3) levels in relation to breast cancer risk factors: a cross-sectional study

    Science.gov (United States)

    Diorio, Caroline; Brisson, Jacques; Bérubé, Sylvie; Pollak, Michael

    2008-01-01

    Introduction Levels of insulin-like growth factor (IGF)-I and its main binding protein (IGFBP-3) have been associated with breast cancer risk among premenopausal women. However, associations of IGFBP-3 levels with breast cancer risk have been inconsistent, possibly due to the different predominant forms of circulating IGFBP-3 (intact versus fragmented) that were measured in these studies. Here, we examine the association of breast cancer risk factors with intact and total IGFBP-3 levels. Methods This cross-sectional study includes 737 premenopausal women recruited at screening mammography. Plasma intact and total IGFBP-3 and IGF-I levels were measured by enzyme-linked immunosorbent assay methods. Percent and absolute breast density were estimated using a computer-assisted method. The associations were evaluated using generalized linear models and Pearson (r) or Spearman (rs) partial correlation coefficients. Results Means ± standard deviations of intact and total IGFBP-3 levels (ng/mL) were 1,044 ± 234 and 4,806 ± 910, respectively. Intact and total IGFBP-3 levels were correlated with age and smoking. Levels of intact IGFBP-3 were negatively correlated with waist-to-hip ratio (WHR) (r = -0.128; P = 0.0005), parity (rs = -0.078; P = 0.04), and alcohol intake (r = -0.137; P = 0.0002) and positively correlated with energy intake (r = 0.075; P = 0.04). In contrast, total IGFBP-3 levels were positively correlated with WHR (r = 0.115; P = 0.002), parity (rs = 0.089; P = 0.02), body mass index (BMI) (r = 0.115; P = 0.002), physical activity (r = 0.118; P = 0.002), and IGF-I levels (r = 0.588; P total (intact and fragmented) IGFBP-3 levels. These findings suggest that different molecular forms of IGFBP-3 may bear different relations to premenopausal breast cancer risk. PMID:18471292

  7. Stromal endothelin B receptor-deficiency inhibits breast cancer growth and metastasis

    OpenAIRE

    Binder, Claudia; Hagemann, Thorsten; Sperling, Swetlana; Schulz, Matthias; Pukrop, Tobias; Grimshaw, Matthew J; Ehrenreich, Hannelore

    2009-01-01

    The endothelin (ET) axis, often deregulated in cancers, is a promising target for anticancer strategies. While previous investigations have focussed mostly on ET action in malignant cells, we chose a model, allowing separate assessment of the effects of ETs and their receptors ETAR and ETBR in the tumor cells and the stromal compartment, which is increasingly recognized as a key player in cancer progression. In homozygous spotting lethal rats (sl/sl), a model of constitutive ETBR-deficiency, ...

  8. LXY6090 – a novel manassantin A derivative – limits breast cancer growth through hypoxia-inducible factor-1 inhibition

    Science.gov (United States)

    Lai, Fangfang; Liu, Qian; Liu, Xiaoyu; Ji, Ming; Xie, Ping; Chen, Xiaoguang

    2016-01-01

    Hypoxia-inducible factor-1 (HIF-1) represents a novel antitumor target owing to its involvement in vital processes considered hallmarks of cancer phenotypes. Manassantin A (MA) derived from Saururus cernuus has been reported as a selective HIF-1 inhibitor. Herein, the structure of MA was optimized to achieve new derivatives with simple chemical properties while retaining its activity. LXY6090 was designed to replace the central tetrahydrofuran moiety of MA with a cyclopentane ring and was identified as a potent HIF-1 inhibitor with an IC50 value of 4.11 nM. It not only inhibited the activity of HIF-1 in breast cancer cells but also downregulated the protein level of HIF-1α, which depended on von Hippel–Lindau for proteasome degradation. The related biological evaluation showed that the activity of HIF-1 target genes, VEGF and IGF-2, was decreased by LXY6090 in breast cancer cell lines. LXY6090 presented potent antitumor activity in vitro. Furthermore, LXY6090 showed in vivo anticancer efficacy by decreasing the HIF-1α expression in nude mice bearing MX-1 tumor xenografts. In conclusion, our data provide a basis for the future development of the novel compound LXY6090 as a potential therapeutic agent for breast cancer. PMID:27445487

  9. Targeting the EGFR/PCNA signaling suppresses tumor growth of triple-negative breast cancer cells with cell-penetrating PCNA peptides.

    Directory of Open Access Journals (Sweden)

    Yung-Luen Yu

    Full Text Available Tyrosine 211 (Y211 phosphorylation of proliferation cell nuclear antigen (PCNA coincides with pronounced cancer cell proliferation and correlates with poor survival of breast cancer patients. In epidermal growth factor receptor (EGFR tyrosine kinase inhibitor (TKI-resistant cells, both nuclear EGFR (nEGFR expression and PCNA Y211 phosphorylation are increased. Moreover, the resistance to EGFR TKI is a major clinical problem in treating EGFR-overexpressing triple-negative breast cancer (TNBC. Thus, effective treatment to combat resistance is urgently needed. Here, we show that treatment of cell-penetrating PCNA peptide (CPPP inhibits growth and induces apoptosis of human TNBC cells. The Y211F CPPP specifically targets EGFR and competes directly for PCNA tyrosine Y211 phosphorylation and prevents nEGFR from binding PCNA in vivo; it also suppresses tumor growth by sensitizing EGFR TKI resistant cells, which have enhanced nEGFR function and abrogated classical EGFR membrane signaling. Furthermore, we identify an active motif of CPPP, RFLNFF (RF6 CPPP, which is necessary and sufficient to inhibit TKI-resistant TNBC cell growth of orthotopic implanted tumor in mice. Finally, the activity of its synthetic retro-inverted derivative, D-RF6 CPPP, on an equimolar basis, is more potent than RF6 CPPP. Our study reveals a drug candidate with translational potential for the future development of safe and effective therapeutic for EGFR TKI resistance in TNBC.

  10. Effects of the knockdown of death-associated protein 3 expression on cell adhesion, growth and migration in breast cancer cells.

    Science.gov (United States)

    Wazir, Umar; Sanders, Andrew J; Wazir, Ahmad M A; Ye, Lin; Jiang, Wen G; Ster, Irina C; Sharma, Anup K; Mokbel, Kefah

    2015-05-01

    The death-associated protein 3 (DAP3) is a highly conserved phosphoprotein involved in the regulation of autophagy. A previous clinical study by our group suggested an association between low DAP3 expression and clinicopathological parameters of human breast cancer. In the present study, we intended to determine the role of DAP3 in cancer cell behaviour in the context of human breast cancer. We developed knockdown sub-lines of MCF7 and MDA-MB-231, and performed growth, adhesion, invasion assays and electric cell-substrate impedance sensing (ECIS) studies of post-wound migration of the cells. In addition, we studied the mRNA expression of caspase 8 and 9, death ligand signal enhancer (DELE), IFN-β promoter stimulator 1 (IPS1), cyclin D1 and p21 in the control and knockdown sub-lines. The knockdown sub-lines of MCF7 and MDA-MB-231 had significantly increased adhesion and decreased growth when compared to the controls. Furthermore, invasion and migration were significantly increased in the MDA-MB-231DAP3kd cells vs. the controls. The expression of caspase 9 and IPS1, known components of the apoptosis pathway, were significantly reduced in the MCF7DAP3kd cells (p=0.05 and p=0.003, respectively). We conclude that DAP3 silencing contributes to breast carcinogenesis by increasing cell adhesion, migration and invasion. It is possible that this may be due to the activity of focal adhesion kinase further downstream of the anoikis pathway. Further research in this direction would be beneficial in increasing our understanding of the mechanisms underlying human breast cancer. PMID:25738636

  11. Targeting metabolism in breast cancer: How far we can go?

    Science.gov (United States)

    Long, Jing-Pei; Li, Xiao-Na; Zhang, Feng

    2016-02-10

    Adjuvant therapies for breast cancer have achieved great success in recent years and early breast cancer is now a curable or chronic disease. Targeted therapies, including endocrine therapy and human epidermal growth factor receptor-2 targeted therapy, marked a new era of breast cancer treatment. However, except for chemotherapy, an efficient drug treatment to improve the overall survival of breast cancer patients is still lacking for triple negative breast cancer. Furthermore, a certain proportion of breast cancer patients present with resistance to drug therapy, making it much more difficult to control the deterioration of the disease. Recently, altered energy metabolism has become one of the hallmarks of cancer, including breast cancer, and it may be linked to drug resistance. Targeting cellular metabolism is becoming a promising strategy to overcome drug resistance in cancer therapy. This review discusses metabolic reprogramming in breast cancer and the possible complex mechanism of modulation. We also summarize the recent advances in metabolic therapy targeted glycolysis, glutaminolysis and fatty acids synthesis in breast cancer. PMID:26862496

  12. Clofarabine, a novel adenosine analogue, reactivates DNA methylation-silenced tumour suppressor genes and inhibits cell growth in breast cancer cells.

    Science.gov (United States)

    Lubecka-Pietruszewska, Katarzyna; Kaufman-Szymczyk, Agnieszka; Stefanska, Barbara; Cebula-Obrzut, Barbara; Smolewski, Piotr; Fabianowska-Majewska, Krystyna

    2014-01-15

    Clofarabine (2-chloro-2'-fluoro-2'-deoxyarabinosyladenine, ClF) is a second-generation 2'-deoxyadenosine analogue that is structurally related to cladribine (2-chloro-2'-deoxyadenosine, 2CdA) and fludarabine (9-beta-d-arabinosyl-2-fluoroadenine, F-ara-A). It demonstrates potent antitumour activity at much lower doses than parent compounds with high therapeutic efficacy in paediatric blood cancers. Our previous studies in breast cancer cells indicate that 2CdA and F-ara-A are involved in epigenetic regulation of gene transcription. We therefore investigated whether ClF influences methylation and expression of selected tumour suppressor genes, such as adenomatous polyposis coli (APC), phosphatase and tensin homologue (PTEN), and retinoic acid receptor beta 2 (RARbeta2), as well as expression of p53, p21 and DNA methyltransferase 1 (DNMT1) in MCF-7 and MDA-MB-231 breast cancer cell lines with different invasive potential. Promoter methylation and gene expression were estimated using methylation-sensitive restriction analysis (MSRA) and real-time PCR, respectively. ClF demonstrated potent growth inhibitory activity in MCF-7 and MDA-MB-231 cells after 96h treatment with IC50 determined as equal to 640nM and 50nM, respectively. In both breast cancer cell lines, ClF led to hypomethylation and up-regulation of APC, PTEN and RARbeta2 as well as increase in p21 expression. Only in non-invasive MCF-7 cells, these changes were associated with down-regulation of DNMT1. Our results provide first evidence of ClF implications in epigenetic regulation of transcriptional activity of selected tumour suppressor genes in breast cancer. It seems to be a new important element of ClF anticancer activity and may indicate its potential efficacy in epigenetic therapy of solid tumours, especially at early stages of carcinogenesis. PMID:24296317

  13. Breast Cancer and Women with Disabilities

    Science.gov (United States)

    ... What's this? Submit Button Past Emails CDC Features Breast Cancer and Women with Disabilities Language: English Español (Spanish) ... years old, get a mammogram every two years. Breast cancer is the most common cancer in women. And ...

  14. The Marine-Derived Sipholenol A-4-O-3′,4′-Dichlorobenzoate Inhibits Breast Cancer Growth and Motility in Vitro and in Vivo through the Suppression of Brk and FAK Signaling

    Directory of Open Access Journals (Sweden)

    Mohamed R. Akl

    2014-04-01

    Full Text Available Sipholenol A is a natural sipholane triterpenoid isolated from the Red Sea sponge, Callyspongia siphonella. Previous studies showed the antimigratory and antiproliferative activities of the semisynthetic sipholenol A esters against breast cancer cell lines. This study investigated the effects of sipholenol A-4-O-3′,4′-dichlorobenzoate (SPA on the growth, migration and invasion of diverse human breast cancer cells. Results showed that SPA inhibited the growth of the human breast cancer cells, MDA-MB-231, MCF-7, BT-474 and T-47D, in a dose-dependent manner. Immunofluorescent analysis showed that SPA significantly reduced Ki-67-positive cells in MDA-MB-231 cells. Flow cytometry and Western blot analyses revealed that SPA treatment suppressed MDA-MB-231 cell growth by inducing cell cycle arrest at the G1 phase. In addition, SPA suppressed breast cancer cell migration, invasion and decreased Brk and FAK activation in a dose-dependent manner. Molecular docking study suggested a perfect fitting at the FAK’s FERM domain, inhibiting the main autophosphorylation site, Y397, which was further confirmed by Western blot analysis. Most known small molecule FAK inhibitors target the kinase domain, creating several off-target side effects. The in vivo studies showed that SPA treatment suppressed breast tumor growth and Ki-67, CD31, p-Brk and p-FAK expression in orthotopic breast cancer in nude mice. In conclusion, SPA inhibited the growth, invasion and migration of breast cancer cells possibly via deactivating Brk and FAK signaling, suggesting good potential for therapeutic use to control invasive breast cancer.

  15. Role of ornithine decarboxylase in regulation of estrogen receptor alpha expression and growth in human breast cancer cells

    OpenAIRE

    Zhu, Qingsong; Jin, Lihua; CASERO, ROBERT A.; Davidson, Nancy E.; Huang, Yi

    2012-01-01

    Our previous studies demonstrated that specific polyamine analogues, oligoamines, down-regulated the activity of a key polyamine biosynthesis enzyme, ornithine decarboxylase (ODC), and suppressed expression of estrogen receptor alpha (ERα) in human breast cancer cells. However, the mechanism underlying the potential regulation of ERα expression by polyamine metabolism has not been explored. Here, we demonstrated that RNAi-mediated knockdown of ODC (ODC KD) down-regulated the polyamine pool, a...

  16. Hypoxia and oxidative stress in breast cancer: Oxidative stress: its effects on the growth, metastatic potential and response to therapy of breast cancer

    OpenAIRE

    Brown, Nicholas S; Bicknell, Roy

    2001-01-01

    Reactive oxygen species (ROS) damage DNA, but the role of ROS in breast carcinoma may not be limited to the mutagenic activity that drives carcinoma initiation and progression. Carcinoma cells in vitro and in vivo are frequently under persistent oxidative stress. In the present review, we outline potential causes of oxygen radical generation within carcinoma cells and explore the possible impact of oxidative stress on the clinical outcome of breast carcinoma.

  17. Hypoxia and oxidative stress in breast cancer: Oxidative stress: its effects on the growth, metastatic potential and response to therapy of breast cancer

    International Nuclear Information System (INIS)

    Reactive oxygen species (ROS) damage DNA, but the role of ROS in breast carcinoma may not be limited to the mutagenic activity that drives carcinoma initiation and progression. Carcinoma cells in vitro and in vivo are frequently under persistent oxidative stress. In the present review, we outline potential causes of oxygen radical generation within carcinoma cells and explore the possible impact of oxidative stress on the clinical outcome of breast carcinoma

  18. Molecular imaging of human breast cancer xenografts in nude mice by epidermal growth factor labelled by near infrared fluorescent dye

    International Nuclear Information System (INIS)

    Objective: This work was to determine the feasibility of using epidermal growth factor (EGF) labeled with a near-infrared fluorescent (NIRF) dye (Cy5.5) to selectively localize and image epidermal growth factor receptor (EGFR)of the human breast cancer. Methods: MDA-MB-231 of human mammary adenocarcinoma and MDA-MB-435S of human mammary ductal carcinoma were detected using a flow cytometry. Laser confocal microscopy was used to examine the intake of EGF-Cy5.5 by MDA-MB-231 and MDA-MB-435S cells. MDA-MB-231 and MDA-MB435S human breast cancer orthotopic xenograft nude mice models were established. In vivo NIRF imaging was acquired after intravenous injection of EGF-Cy5.5 (1 nmol/0.2 ml)immediately and different time intervals. The up-take of EGF-Cy5.5 in MDA-MB-231 and MDA-MB-435S was detected using ROI technique. The blockage of the monocolonal antibody C225 to the EGF-Cy5.5 uptake were observed in viovo and ex vivo. Ex vivo tumor tissue fluorescent imaging was executed and the histological sections were stained by HE method for pathobiology assay. Student t test was used for statistical analysis with SPSS for Windows. Results: Flow cytometry indicated the EGFR expression percentage of MDA-MB-231 was 41.96% and the percentage of MDA-MB-435S was 0.12%. The fluorescence showed that the uptake of EGF-Cy5.5 by MDA-MB-231 cells could be observed by the laser confocal microscopy. There was no specific uptake of EGF-Cy5.5 by MDA-MB-435S. In vivo NIRF images showed mean fluorescence intensity in MDA-MB-231 tumors was (38 220±3 144)au, which was significantly higher than MDA-MB435S's ( 11 885 + 1 144 ) au (t = 17. 600, P < 0.01) or normal region' s (11 980 ±1 496) au(t=17. 491, P<0.01) at 24 h postinjection of EGF-Cy5.5. The mean fluorescence intensity was significantly reduced in MDA-MB-231 group with preadministration of C225, whose mean intensity was (10 472±842) au (t=16.772, P<0.01), while the mean intensity was not apparently decreased in MDA-MB-435S block group

  19. miR-34a Silences c-SRC to Attenuate Tumor Growth in Triple-Negative Breast Cancer.

    Science.gov (United States)

    Adams, Brian D; Wali, Vikram B; Cheng, Christopher J; Inukai, Sachi; Booth, Carmen J; Agarwal, Seema; Rimm, David L; Győrffy, Balázs; Santarpia, Libero; Pusztai, Lajos; Saltzman, W Mark; Slack, Frank J

    2016-02-15

    Triple-negative breast cancer (TNBC) is an aggressive subtype with no clinically proven biologically targeted treatment options. The molecular heterogeneity of TNBC and lack of high frequency driver mutations other than TP53 have hindered the development of new and effective therapies that significantly improve patient outcomes. miRNAs, global regulators of survival and proliferation pathways important in tumor development and maintenance, are becoming promising therapeutic agents. We performed miRNA-profiling studies in different TNBC subtypes to identify miRNAs that significantly contribute to disease progression. We found that miR-34a was lost in TNBC, specifically within mesenchymal and mesenchymal stem cell-like subtypes, whereas expression of miR-34a targets was significantly enriched. Furthermore, restoration of miR-34a in cell lines representing these subtypes inhibited proliferation and invasion, activated senescence, and promoted sensitivity to dasatinib by targeting the proto-oncogene c-SRC. Notably, SRC depletion in TNBC cell lines phenocopied the effects of miR-34a reintroduction, whereas SRC overexpression rescued the antitumorigenic properties mediated by miR-34a. miR-34a levels also increased when cells were treated with c-SRC inhibitors, suggesting a negative feedback exists between miR-34a and c-SRC. Moreover, miR-34a administration significantly delayed tumor growth of subcutaneously and orthotopically implanted tumors in nude mice, and was accompanied by c-SRC downregulation. Finally, we found that miR-34a and SRC levels were inversely correlated in human tumor specimens. Together, our results demonstrate that miR-34a exerts potent antitumorigenic effects in vitro and in vivo and suggests that miR-34a replacement therapy, which is currently being tested in human clinical trials, represents a promising therapeutic strategy for TNBC. PMID:26676753

  20. Quality indicators for breast cancer

    DEFF Research Database (Denmark)

    Poortmans, Philip; Aznar, Marianne; Bartelink, Harry

    2012-01-01

    Radiation therapy for breast cancer has considerably changed over the years, from simple simulator-based 2-dimensional techniques to sophisticated image-guided individualized treatments, with maximally protected normal structures. This has led to a substantial improvement in the outcome of breast...

  1. Consumer Health Education. Breast Cancer.

    Science.gov (United States)

    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,…

  2. Tumor-suppressor activity of RRIG1 in breast cancer

    International Nuclear Information System (INIS)

    Retinoid receptor-induced gene-1 (RRIG1) is a novel gene that has been lost in several types of human cancers. The aim of this study was to determine whether RRIG1 plays a role in breast cancer, such as in the suppression of breast cancer cell growth and invasion. Immunohistochemistry was used to detect RRIG1 expression in breast tissue specimens. Gene transfection was used to restore or knock down RRIG1 expression in breast cancer cell lines for analysis of cell viability, colony formation, and migration/invasion potential. Reverse-transcription polymerase chain reaction and western blot assays were used to detect the changes in gene expression. The RhoA activation assay was used to assess RRIG1-induced inhibition of RhoA activity. The immunohistochemical data showed that RRIG1 expression was reduced in breast cancer tissues compared with normal and atypical hyperplastic breast tissues. RRIG1 expression was inversely correlated with lymph node metastasis of breast cancer but was not associated with the status of hormone receptors, such as estrogen receptor, progesterone receptor, or HER2. Furthermore, restoration of RRIG1 expression inhibited proliferation, colony formation, migration, and invasion of breast cancer cells. Expression of RRIG1 also reduced phosphorylated Erk1/2 and Akt levels; c-Jun, MMP9, and Akt expressions; and RhoA activity. In contrast, knockdown of RRIG1 expression promoted breast cancer cell proliferation, colony formation, migration, and invasion potential. The data from the current study indicated that RRIG1 expression was reduced or lost in breast cancer and that restoration of RRIG1 expression suppressed breast cancer cell growth and invasion capacity. Future studies will determine the underlying molecular mechanisms and define RRIG1 as a tumor-suppressor gene in breast cancer

  3. Male breast cancer.

    Science.gov (United States)

    Ottini, Laura; Palli, Domenico; Rizzo, Sergio; Federico, Mario; Bazan, Viviana; Russo, Antonio

    2010-02-01

    Male breast cancer (MaleBC) is a rare disease, accounting for development; low-penetrance gene mutations (i.e. CHEK-2) are more common but involve a lower risk increase. About 90% of all male breast tumors have proved to be invasive ductal carcinomas, expressing high levels of hormone receptors with evident therapeutic returns. The most common clinical sign of BC onset in men is a painless palpable retroareolar lump, which should be evaluated by means of mammography, ultrasonography and core biopsy or fine needle aspiration (FNA). To date, there are no published data from prospective randomized trials supporting a specific therapeutic approach in MaleBC. Tumor size together with the number of axillary nodes involved are the main prognostic factors and should guide the treatment choice. Locoregional approaches include surgery and radiotherapy (RT), depending upon the initial clinical presentation. When systemic treatment (adjuvant, neoadjuvant and metastatic) is delivered, the choice between hormonal and or chemotherapy (CT) should depend upon the clinical and biological features, according to the FBC management guidelines. However great caution is required because of high rates of age-related comorbidities. PMID:19427229

  4. Mammographic screening for breast cancer: A review

    OpenAIRE

    Lee, Warwick; Peters, Gudrun

    2013-01-01

    In 2011, BreastScreen Australia celebrated 20 years of mammographic screening for breast cancer in Australia. There has been a reduction in mortality from breast cancer over the last two decades, coincident with mammographic screening. However, there are concerns that mammographic screening may result in overdiagnosis of breast cancer and that the reduction in mortality from breast cancer is the result of better treatment rather than screening. This article reviews the evidence on which mammo...

  5. Insulin-like growth factors (IGFs) stimulate the release of alpha 1-antichymotrypsin and soluble IGF-II/mannose 6-phosphate receptor from MCF7 breast cancer cells.

    Science.gov (United States)

    Confort, C; Rochefort, H; Vignon, F

    1995-09-01

    The growth of hormone-responsive MCF7 human breast cancer cells is controlled by steroid hormones and growth factors. By metabolic labeling of cells grown in steroid- and growth factor-stripped serum conditions, we show that insulin-like growth factors (IGF-I and IGF-II) increase by approximately 5-fold the release of several proteins including cathepsin D, alpha 1-antichymotrypsin, and soluble forms of the multifunctional IGF-II/mannose 6-phosphate (M6P) receptor. Two soluble forms of IGF-II/M6P receptors were detected, one major (approximately 260 kilodaltons) and one minor (approximately 85 kilodaltons) that probably represents a proteolytic fragment of the larger soluble molecule. IGFs increased receptor release in a dose-dependent fashion with 50-60% of newly synthesized receptor released at 5-10 nM IGFs. The release of IGF-II/M6P receptors correlated with the levels of secreted cathepsin D in different human breast cancer cells or in rats stable transfectants that are constitutively expressing variable levels of human cathepsin D. IGFs had a stronger effect on IGF-II/M6P receptor release, whereas estradiol treatment preferentially enhanced the release of protease and antiprotease. We thus demonstrate that in human breast cancer cells, IGFs not only act as strong mitogens but also regulate release of alpha 1-antichymotrypsin, IGF-II/M6P-soluble receptor, and cathepsin D; three proteins that potentially regulate cell proliferation and/or invasion. PMID:7649082

  6. Preventing Breast Cancer: Making Progress

    Science.gov (United States)

    ... linking the development of this disease, in many cases, with exposure to the hormone estrogen. The focus of recent breast cancer prevention studies has been on testing the effectiveness of drugs called selective estrogen receptor modulators (SERMs). SERMs are ...

  7. Palbociclib for Advanced Breast Cancer

    Science.gov (United States)

    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.

  8. Stages of Male Breast Cancer

    Science.gov (United States)

    ... exposure, high levels of estrogen, and a family history of breast cancer can increase a man’s risk ... also show the dimpled appearance called peau d’orange (like the skin of an orange). There may ...

  9. Treatment Option Overview (Breast Cancer)

    Science.gov (United States)

    ... trials is available from the NCI website . Locally Advanced or Inflammatory Breast Cancer Treatment of locally advanced ... NIH). NIH is the federal government’s center of biomedical research. The PDQ summaries are based on an ...

  10. Dormancy in breast cancer

    Directory of Open Access Journals (Sweden)

    Banys M

    2012-12-01

    Full Text Available Malgorzata Banys,1,2 Andreas D Hartkopf,1 Natalia Krawczyk,1 Tatjana Kaiser,1 Franziska Meier-Stiegen,1 Tanja Fehm,1 Hans Neubauer11Department of Obstetrics and Gynecology, University of Tuebingen, Tuebingen, Germany; 2Department of Obstetrics and Gynecology, Marienkrankenhaus Hamburg, Hamburg, GermanyAbstract: Tumor dormancy describes a prolonged quiescent state in which tumor cells are present, but disease progression is not yet clinically apparent. Breast cancer is especially known for long asymptomatic periods, up to 25 years, with no evidence of the disease, followed by a relapse. Factors that determine the cell's decision to enter a dormant state and that control its duration remain unclear. In recent years, considerable progress has been made in understanding how tumor cells circulating in the blood interact and extravasate into secondary sites and which factors might determine whether these cells survive, remain dormant, or become macrometastases. The mechanisms of tumor cell dormancy are still not clear. Two different hypotheses are currently discussed: tumor cells persist either by completely withdrawing from the cell cycle or by continuing to proliferate at a slow rate that is counterbalanced by cell death. Because dormant disseminated tumor cells may be the founders of metastasis, one hypothesis is that dormant tumor cells, or at least a fraction of them, share stem cell-like characteristics that may be responsible for their long half-lives and their suggested resistance to standard chemotherapy. Therefore, knowledge of the biology of tumor cell dormancy may be the basis from which to develop innovative targeted therapies to control or eliminate this tumor cell fraction. In this review, we discuss biological mechanisms and clinical implications of tumor dormancy in breast cancer patients.Keywords: tumor dormancy, disseminated tumor cell, circulating tumor cell, targeted therapy

  11. ARF6 promotes the formation of Rac1 and WAVE-dependent ventral F-actin rosettes in breast cancer cells in response to epidermal growth factor.

    Directory of Open Access Journals (Sweden)

    Valentina Marchesin

    Full Text Available Coordination between actin cytoskeleton assembly and localized polarization of intracellular trafficking routes is crucial for cancer cell migration. ARF6 has been implicated in the endocytic recycling of surface receptors and membrane components and in actin cytoskeleton remodeling. Here we show that overexpression of an ARF6 fast-cycling mutant in MDA-MB-231 breast cancer-derived cells to mimick ARF6 hyperactivation observed in invasive breast tumors induced a striking rearrangement of the actin cytoskeleton at the ventral cell surface. This phenotype consisted in the formation of dynamic actin-based podosome rosette-like structures expanding outward as wave positive for F-actin and actin cytoskeleton regulatory components including cortactin, Arp2/3 and SCAR/WAVE complexes and upstream Rac1 regulator. Ventral rosette-like structures were similarly induced in MDA-MB-231 cells in response to epidermal growth factor (EGF stimulation and to Rac1 hyperactivation. In addition, interference with ARF6 expression attenuated activation and plasma membrane targeting of Rac1 in response to EGF treatment. Our data suggest a role for ARF6 in linking EGF-receptor signaling to Rac1 recruitment and activation at the plasma membrane to promote breast cancer cell directed migration.

  12. pH-responsive artemisinin derivatives and lipid nanoparticle formulations inhibit growth of breast cancer cells in vitro and induce down-regulation of HER family members.

    Directory of Open Access Journals (Sweden)

    Yitong J Zhang

    Full Text Available Artemisinin (ART dimers show potent anti-proliferative activities against breast cancer cells. To facilitate their clinical development, novel pH-responsive artemisinin dimers were synthesized for liposomal nanoparticle formulations. A new ART dimer was designed to become increasingly water-soluble as pH declines. The new artemisinin dimer piperazine derivatives (ADPs remained tightly associated with liposomal nanoparticles (NPs at neutral pH but were efficiently released at acidic pH's that are known to exist within solid tumors and organelles such as endosomes and lysosomes. ADPs incorporated into nanoparticles down regulated the anti-apoptotic protein, survivin, and cyclin D1 when incubated at low concentrations with breast cancer cell lines. We demonstrate for the first time, for any ART derivative, that ADP NPs can down regulate the oncogenic protein HER2, and its counterpart, HER3 in a HER2+ cell line. We also show that the wild type epidermal growth factor receptor (EGFR or HER1 declines in a triple negative breast cancer (TNBC cell line in response to ADP NPs. The declines in these proteins are achieved at concentrations of NP109 at or below 1 µM. Furthermore, the new artemisinin derivatives showed improved cell-proliferation inhibition effects compared to known dimer derivatives.

  13. Can Breast Cancer in Men Be Found Early?

    Science.gov (United States)

    ... BRCA mutations, including prostate cancer , pancreatic cancer , and testicular cancer . Because breast cancer in men can be caused ... Breast Cancer In Men? Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treating Breast Cancer ...

  14. 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

    Science.gov (United States)

    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

  15. Leptomeningeal metastases in breast cancer

    OpenAIRE

    Scott, Brian J.; Kesari, Santosh

    2013-01-01

    Central nervous system (CNS) metastasis from breast cancer may be characterized as either parenchymal brain metastasis (BM) or leptomeningeal (LM) metastasis. BM are much more common (about 80% of all CNS metastases), and have been more extensively studied than LM. CNS metastasis in breast cancer has been associated with reduced overall survival, with the shortest survival generally observed in cases of LM. Here, we review the epidemiology, prognostic factors, diagnostic tools, currently avai...

  16. Update on inflammatory breast cancer

    OpenAIRE

    Lerebours, Florence; Bieche, Ivan; Lidereau, Rosette

    2005-01-01

    Inflammatory breast cancer (IBC) is both the least frequent and the most severe form of epithelial breast cancer. The diagnosis is based on clinical inflammatory signs and is reinforced by pathological findings. Significant progress has been made in the management of IBC in the past 20 years. Yet survival among IBC patients is still only one-half that among patients with non-IBC. Identification of the molecular determinants of IBC would probably lead to more specific treatments and to improve...

  17. Endobronchial metastasis in breast cancer.

    OpenAIRE

    Albertini, R E; Ekberg, N L

    1980-01-01

    Ten patients with endobronchial metastasis from primary breast cancer were found among 1200 fibreoptic bronchoscopies. Six of these patients had radiological signs suggesting bronchial obstruction. The diagnosis was verified in nine cases by means of bronchoscopic biopsy or cytology and in one by thoracotomy. Endobronchial metastasis should be considered when symptoms or chest films suggest endobronchial disease in a patient with a history of breast cancer.

  18. Chronic morphine treatment attenuates cell growth of human BT474 breast cancer cells by rearrangement of the ErbB signalling network.

    Directory of Open Access Journals (Sweden)

    Inka Regine Weingaertner

    Full Text Available There is increasing evidence that opioid analgesics may interfere with tumour growth. It is currently thought that these effects are mediated by transactivation of receptor tyrosine kinase (RTK-controlled ERK1/2 and Akt signalling. The growth of many breast cancer cells is dependent on hyperactive ErbB receptor networks and one of the most successful approaches in antineoplastic therapy during the last decade was the development of ErbB-targeted therapies. However, the response rates of single therapies are often poor and resistance mechanisms evolve rapidly. To date there is no information about the ability of opioid analgesics to interfere with the growth of ErbB-driven cancers.Here we demonstrate that ErbB2 overexpressing BT474 human breast cancer cells carry fully functional endogenous µ-opioid receptors. Most interestingly, the acute opioid effects on basal and Heregulin-stimulated ERK1/2 and Akt phosphorylation changed considerably during chronic Morphine treatment. Investigation of the underlying mechanism by the use of protein kinase inhibitors and co-immunoprecipitation studies revealed that chronic Morphine treatment results in rearrangement of the ErbB signalling network leading to dissociation of ERK1/2 from Akt signalling and a switch from ErbB1/ErbB3 to ErbB1/ErbB2-dependent cell growth. In chronically Morphine-treated cells Heregulin-stimulated ERK1/2 signalling is redirected via a newly established PI3K- and metalloproteinase-dependent feedback loop. Together, these alterations result in apoptosis of BT474 cells. A similar switch in Heregulin-stimulated ERK1/2 signalling from an ErbB2-independent to an ErbB2-, PI3K- and metalloproteinase-dependent mechanism was also observed in κ-opioid receptor expressing SKBR3 human mammary adenocarcinoma cells.The present data demonstrate that the ErbB receptor network of human breast cancer cells represents a target for chronic Morphine treatment. Rearrangement of ErbB signalling by chronic

  19. Short-hairpin RNA-mediated Heat shock protein 90 gene silencing inhibits human breast cancer cell growth in vitro and in vivo

    International Nuclear Information System (INIS)

    Highlights: ► Hsp90 is over-expressed in human breast cancer. ► The shRNA-mediated gene silencing of Hsp90 resulted in inhibition of cell growth. ► Akt and NF-kB were down-regulation after transfection due to Hsp90 silencing. ► The tumor growth ratio was decline due to Hsp90 silencing. ► The PCNA expression was down-regulation due to Hsp90 silencing. -- Abstract: Hsp90 interacts with proteins that mediate signaling pathways involved in the regulation of essential processes such as proliferation, cell cycle control, angiogenesis and apoptosis. Hsp90 inhibition is therefore an attractive strategy for blocking abnormal pathways that are crucial for cancer cell growth. In the present study, the role of Hsp90 in human breast cancer MCF-7 cells was examined by stably silencing Hsp90 gene expression with an Hsp90-silencing vector (Hsp90-shRNA). RT-PCR and Western blot analyses showed that Hsp90-shRNA specifically and markedly down-regulated Hsp90 mRNA and protein expression. NF-kB and Akt protein levels were down-regulated in Hsp90-shRNA transfected cells, indicating that Hsp90 knockout caused a reduction of survival factors and induced apoptosis. Treatment with Hsp90-shRNA significantly increased apoptotic cell death and caused cell cycle arrest in the G1/S phase in MCF-7 cells, as shown by flow cytometry. Silencing of Hsp90 also reduced cell viability, as determined by MTT assay. In vivo experiments showed that MCF-7 cells stably transfected with Hsp90-shRNA grew slowly in nude mice as compared with control groups. In summary, the Hsp90-shRNA specifically silenced the Hsp90 gene, and inhibited MCF-7 cell growth in vitro and in vivo. Possible molecular mechanisms underlying the effects of Hsp90-shRNA include the degradation of Hsp90 breast cancer-related client proteins, the inhibition of survival signals and the upregulation of apoptotic pathways. shRNA-mediated interference may have potential therapeutic utility in human breast cancer.

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

    Science.gov (United States)

    2016-04-06

    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

  1. Metformin attenuates transforming growth factor beta (TGF-β) mediated oncogenesis in mesenchymal stem-like/claudin-low triple negative breast cancer.

    Science.gov (United States)

    Wahdan-Alaswad, Reema; Harrell, J Chuck; Fan, Zeying; Edgerton, Susan M; Liu, Bolin; Thor, Ann D

    2016-01-01

    Mesenchymal stem-like/claudin-low (MSL/CL) breast cancers are highly aggressive, express low cell-cell adhesion cluster containing claudins (CLDN3/CLDN4/CLDN7) with enrichment of epithelial-to-mesenchymal transition (EMT), immunomodulatory, and transforming growth factor-β (TGF-β) genes. We examined the biological, molecular and prognostic impact of TGF-β upregulation and/or inhibition using in vivo and in vitro methods. Using publically available breast cancer gene expression databases, we show that upregulation and enrichment of a TGF-β gene signature is most frequent in MSL/CL breast cancers and is associated with a worse outcome. Using several MSL/CL breast cancer cell lines, we show that TGF-β elicits significant increases in cellular proliferation, migration, invasion, and motility, whereas these effects can be abrogated by a specific inhibitor against TGF-β receptor I and the anti-diabetic agent metformin, alone or in combination. Prior reports from our lab show that TNBC is exquisitely sensitive to metformin treatment. Mechanistically, metformin blocks endogenous activation of Smad2 and Smad3 and dampens TGF-β-mediated activation of Smad2, Smad3, and ID1 both at the transcriptional and translational level. We report the use of ID1 and ID3 as clinical surrogate markers, where high expression of these TGF-β target genes was correlated to poor prognosis in claudin-low patients. Given TGF-β's role in tumorigenesis and immunomodulation, blockade of this pathway using direct kinase inhibitors or more broadly acting inhibitors may dampen or abolish pro-carcinogenic and metastatic signaling in patients with MCL/CL TNBC. Metformin therapy (with or without other agents) may be a heretofore unrecognized approach to reduce the oncogenic activities associated with TGF-β mediated oncogenesis. PMID:26919310

  2. Presence of Insulin-Like Growth Factor Binding Proteins Correlates With Tumor-Promoting Effects of Matrix Metalloproteinase 9 in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jae-Hyun Park

    2015-05-01

    Full Text Available The stroma of breast cancer can promote the disease’s progression, but whether its composition and functions are shared among different subtypes is poorly explored. We compared stromal components of a luminal [mouse mammary tumor virus (MMTV–Neu] and a triple-negative/basal-like [C3(1–Simian virus 40 large T antigen (Tag] genetically engineered breast cancer mouse model. The types of cytokines and their expression levels were very different in the two models, as was the extent of innate immune cell infiltration; however, both models showed infiltration of innate immune cells that expressed matrix metalloproteinase 9 (MMP9, an extracellular protease linked to the progression of many types of cancer. By intercrossing with Mmp9 null mice, we found that the absence of MMP9 delayed tumor onset in the C3(1-Tag model but had no effect on tumor onset in the MMTV-Neu model. We discovered that protein levels of insulin-like growth factor binding protein-1 (IGFBP-1, an MMP9 substrate, were increased in C3(1-Tag;Mmp9−/− compared to C3(1-Tag;Mmp9+/+ tumors. In contrast, IGFBP-1 protein expression was low in MMTV-Neu tumors regardless of Mmp9 status. IGFBP-1 binds and antagonizes IGFs, preventing them from activating their receptors to promote cell proliferation and survival. Tumors from C3(1-Tag;Mmp9−/− mice had reduced IGF-1 receptor phosphorylation, consistent with slower tumor onset. Finally, gene expression analysis of human breast tumors showed that high expression of IGFBP mRNA was strongly correlated with good prognosis but not when MMP9 mRNA was also highly expressed. In conclusion, MMP9 has different effects on breast cancer progression depending on whether IGFBPs are expressed.

  3. Effects of inoculation site and Matrigel on growth and metastasis of human breast cancer cells.

    OpenAIRE

    L. Bao; Matsumura, Y; Baban, D.; Sun, Y.; Tarin, D

    1994-01-01

    The co-injection of extracellular matrix components, such as Matrigel, with human tumour cells into nude mice has been reported to facilitate tumour formation and growth, but it is unknown whether such components exert similar effects on tumour progression and metastasis. Metastatic behaviour is known to be enhanced when tumour cells are implanted orthotopically, and it is inferred that full and efficient expression of this phenotype may involve some interactions with local connective tissue ...

  4. Activation of ErbB3, EGFR and Erk is essential for growth of human breast cancer cell lines with acquired resistance to fulvestrant

    DEFF Research Database (Denmark)

    Frogne, Thomas; Benjaminsen, Rikke V; Sonne-Hansen, Katrine; Sorensen, Boe S; Nexo, Ebba; Laenkholm, Anne-Vibeke; Rasmussen, Louise M; Riese, David J; de Cremoux, Patricia; Stenvang, Jan; Lykkesfeldt, Anne

    2008-01-01

    Seven fulvestrant resistant cell lines derived from the estrogen receptor alpha positive MCF-7 human breast cancer cell line were used to investigate the importance of epidermal growth factor receptor (ErbB1-4) signaling. We found an increase in mRNA expression of EGFR and the ErbB3/ErbB4 ligand...... growth inhibition of two resistant cell lines. These data indicate that ligand activated ErbB3 and EGFR, and Erk signaling play important roles in fulvestrant resistant cell growth. Furthermore, the decreased level of ErbB4 in resistant cells may facilitate heterodimerization of ErbB3 with EGFR and ErbB2....... Our data support that a concerted action against EGFR, ErbB2 and ErbB3 may be required to obtain complete growth suppression of fulvestrant resistant cells....

  5. Exercise training in transgenic mice is associated with attenuation of early breast cancer growth in a dose-dependent manner.

    Directory of Open Access Journals (Sweden)

    Jorming Goh

    Full Text Available Epidemiological research suggests that regular physical activity confers beneficial effects that mediate an anti-tumor response and may reduce cancer recurrence. It is unclear what amount of physical activity is necessary to exert such a protective effect and what mechanisms are involved. We investigated the effects of voluntary wheel running on tumor progression and cytokine gene expression in the transgenic polyoma middle T oncoprotein (PyMT mouse model of invasive breast cancer. Runners showed significantly reduced tumor sizes compared with non-runners after 3 weeks of running (p ≤ 0.01, and the greater the running distance the smaller the tumor size (Pearson's r = -0.61, p ≤ 0.04, R(2 = 0.38. Mice running greater than 150 km per week had a significantly attenuated tumor size compared with non-runners (p ≤ 0.05. Adipose tissue mass was inversely correlated with tumor size in runners (Pearson's r = -0.77, p = 0.014 but not non-runners. Gene expression of CCL22, a cytokine associated with recruitment of immunosuppressive T regulatory cells, was decreased in tumors of runners compared to non-runners (p ≤ 0.005. No differences in tumor burden or metastatic burden were observed between runners and non-runners after ten weeks of running when the study was completed. We conclude that voluntary wheel running in PyMT mice correlates with an attenuation in tumor progression early during the course of invasive breast cancer. This effect is absent in the later stages of overwhelming tumor burden even though cytokine signaling for immunosuppressive regulatory T cells was down regulated. These observations suggest that the initiation of moderate exercise training for adjunctive therapeutic benefit early in the course of invasive breast cancer should be considered for further investigation.

  6. Cytotoxic activity of Macrosolen parasiticus (L. Danser on the growth of breast cancer cell line (MCF-7

    Directory of Open Access Journals (Sweden)

    Vijay Kumar Sodde

    2015-01-01

    Full Text Available Background: Macrosolen parasiticus (L. Danser belonging to Loranthaceaea (mistletoe family is a parasitic plant that grows on different host plants such as mango, jack fruit, peepal, neem tree, etc., This study was aimed to investigate the anti-cancer activity of methanolic and aqueous extract of stem of M. parasiticus. Objectives: To investigate the in vitro cytotoxic potential of the methanolic and aqueous extracts from stems of M. parasiticus against MCF-7 breast cancer cells by brine shrimp lethality (BSL bioassay, MTT assay and sulforhodamine B (SRB assay. Materials and Methods: The extracts were tested in human breast cancer cell lines in vitro for percentage cytotoxicity, apoptosis by acridine orange/ethidium bromide staining, LD 50 and IC 50 values after treatment with M. parasiticus extracts. Results: In BSL bioassay, aqueous extract showed more significant (P < 0.01 cytotoxicity with LD 50 82.79 ± 2.67 μg/mL as compared to methanolic extract with LD 50 125 ± 3.04 μg/mL. The methanolic extract of M. parasiticus showed IC 50 97.33 ± 3.75 μg/mL (MTT (P < 0.05 and 94.58 ± 3.84 μg/mL (SRB (P < 0.01 assays against MCF-7. The aqueous extract of M. parasiticus demonstrated higher activity with IC 50 59.33 ± 3.3 μg/mL (MTT (P < 0.01 and 51.9 ± 1.87 μg/mL (SRB (P < 0.01 assays, after 48 h of exposure and thus showed significant dose-dependent cytotoxic activity. Conclusion: The finding demonstrated that both extracts of M. parasiticus showed significant cytotoxic activity, however aqueous extract demonstrated higher activity against MCF-7 breast cancer cells.

  7. RAD51B in Familial Breast Cancer

    OpenAIRE

    Pelttari, Liisa M.

    2016-01-01

    Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possi...

  8. Proteomic maps of breast cancer subtypes.

    Science.gov (United States)

    Tyanova, Stefka; Albrechtsen, Reidar; Kronqvist, Pauliina; Cox, Juergen; Mann, Matthias; Geiger, Tamar

    2016-01-01

    Systems-wide profiling of breast cancer has almost always entailed RNA and DNA analysis by microarray and sequencing techniques. Marked developments in proteomic technologies now enable very deep profiling of clinical samples, with high identification and quantification accuracy. We analysed 40 oestrogen receptor positive (luminal), Her2 positive and triple negative breast tumours and reached a quantitative depth of >10,000 proteins. These proteomic profiles identified functional differences between breast cancer subtypes, related to energy metabolism, cell growth, mRNA translation and cell-cell communication. Furthermore, we derived a signature of 19 proteins, which differ between the breast cancer subtypes, through support vector machine (SVM)-based classification and feature selection. Remarkably, only three proteins of the signature were associated with gene copy number variations and eleven were also reflected on the mRNA level. These breast cancer features revealed by our work provide novel insights that may ultimately translate to development of subtype-specific therapeutics. PMID:26725330

  9. Lifestyle changes for prevention of breast cancer

    OpenAIRE

    Hashemi, Seyed Hesam Bani; Karimi, Samieh; Mahboobi, Hamidreza

    2014-01-01

    Breast cancer is the second most common cause of death from cancer among women. Lifestyle changes are shown to be important in the prevention of breast cancer. Diet, physical activity, smoking, alcohol use, and vitamin and mineral use are key factors influencing the risk of breast cancer among women. Because these factors are related to each other, it is difficult to assess their individual roles in breast cancer. Some of these factors are alterable, meaning that women can decrease their risk...

  10. Diagnostic Power of Vascular Endothelial Growth Factor and Macrophage Colony-Stimulating Factor in Breast Cancer Patients Based on ROC Analysis

    Directory of Open Access Journals (Sweden)

    Monika Zajkowska

    2016-01-01

    Full Text Available Breast cancer (BC is the most common malignancy in women. Vascular endothelial growth factor (VEGF has been described as an important regulator of angiogenesis which plays a vital role in the progression of tumor. Macrophage colony-stimulating factor (M-CSF is a cytokine whose functions include regulation of hematopoietic lineages cells growth, proliferation, and differentiation. We investigated the diagnostic significance of these parameters in comparison to CA15-3 in BC patients and in relation to the control group (benign breast tumor and healthy women. Plasma levels of the tested parameters were determined by ELISA and CA15-3 was determined by CMIA. VEGF was shown to be comparable to CA15-3 values of sensitivity in BC group and, what is more important, higher values in early stages of BC. VEGF was also the only parameter which has statistically significant AUC in all stages of cancer. M-CSF has been shown to be comparable to CA15-3 and VEGF, specificity, and AUC values only in stages III and IV of BC. These results indicate the usefulness and high diagnostic power of VEGF in the detection of BC. Also, it occurred to be the best candidate for cancer diagnostics in stages I and II of BC and in the differentiation between BC and benign cases.

  11. Clinical usefulness of cancer markers in primary breast cancer

    OpenAIRE

    Verring, A.; A. Clouth; Ziolkowski, P; Oremek, G. M.

    2011-01-01

    The aim of this study was to investigate the diagnostic power of CA 549, MSA and CA 15-3 in identifying breast cancer. The study included 232 patients of which 56 were healthy, 43 had benign breast cancer and 191 with other growths. The results were obtained using a specific immunoassay and using producers' cut offs. The following sensitivity and specificity of markers were found: CA 549 (sen.: 40%/spec.: 90%), MSA (sen.: 22%/spec.: 96%), and CA 15-3 (sen.: 33%/spec.: 86%). Ideal cut offs wer...

  12. High-affinity insulin binding to an atypical insulin-like growth factor-I receptor in human breast cancer cells.

    OpenAIRE

    Milazzo, G.; Yip, C. C.; Maddux, B A; Vigneri, R; Goldfine, I D

    1992-01-01

    We studied the nature of insulin receptor binding in MCF-7 breast cancer cells. In both intact cells and solubilized receptor preparations, high-affinity insulin binding was seen. However, unlabeled insulin-like growth factor-I (IGF-I) was five-fold more potent in inhibiting 125I-insulin binding than insulin itself. With monoclonal antibodies to the insulin receptor, 30% of 125I-insulin binding was inhibited. In contrast when alpha-IR3, a monoclonal antibody that recognizes typical IGF-I rece...

  13. Birth length and weight as predictors of breast cancer prognosis

    Directory of Open Access Journals (Sweden)

    Vatten Lars J

    2010-03-01

    Full Text Available Abstract Background Birth size, and particularly birth length, is positively associated with breast cancer risk in adulthood. The objective of this study was to examine whether birth size is associated with survival among breast cancer patients. Methods Information on birth size (weight, length and ponderal index (kg/length (m3 was collected from birth archives for 331 breast cancer patients who were diagnosed at two university hospitals in Norway (Bergen and Trondheim. The patients were followed from the time of diagnosis until death from breast cancer, death from another cause, or to the end of follow-up, and birth size was related to survival, using Cox regression analysis. Results Breast cancer patients with birth length ≥ 52 cm had nearly twice the risk of dying (hazard ratio, 1.92, 95% confidence interval, 1.09-3.41 from breast cancer compared to women with birth length less than 48 cm, after adjustment for place of birth and year of diagnosis. Similar analyses related to birth weight and ponderal index showed no clear association with breast cancer survival. Conclusions Poorer outcome of breast cancer patients with high birth length may reflect effects of factors that stimulate longitudinal growth and simultaneously increase the risk of metastases and fatal outcome. It is possible that the insulin-like growth factor (IGF system is involved in the underlying mechanisms.

  14. Antibodies to Placental Immunoregulatory Ferritin with Transfer of Polyclonal Lymphocytes Arrest MCF-7 Human Breast Cancer Growth in a Nude Mouse Model

    Directory of Open Access Journals (Sweden)

    Marisa Halpern

    2007-06-01

    Full Text Available The recently cloned human gene named “placental immunoregulatory ferritin” (PLIF is a pregnancyrelated immunomodulator. Recombinant PLIF and its bioactive domain C48 are immune-suppressive and induce pronounced IL-10 production by immune cells. PLIF is expressed in the placenta and breast cancer cells. Blocking PLIF in pregnant mice by anti-C48 antibodies inhibited placental and fetal growth and modulated the cytokine network. It has been revealed that anti-C48 treatment inhibited MCF-7 tumor growth in nude mice. However, this significant effect was observed only in those transfused with human peripheral blood mononuclear cells. Blocking PLIF in tumor-engrafted human immune cell transfused mice resulted in massive infiltration of human CD45+ cells (mainly CD8+ T cells, both intratumorally and in the tumor periphery, and a significant number of caspase-3+ cells. In vitro, antiC48 treatment of MCF-7 tumor cells cocultured with human lymphocytes induced a significant increase in interferon-γ secretion. We conclude that blocking PLIF inhibits breast cancer growth, possibly by an effect on the cytokine network in immune cells and on breakdown of immunosuppression.

  15. Effect of endocrine therapy on growth of T61 human breast cancer xenografts is directly correlated to a specific down-regulation of insulin-like growth factor II (IGF-II)

    DEFF Research Database (Denmark)

    Brünner, N; Yee, D; Kern, F G;

    1993-01-01

    Insulin-like growth factors I and II (IGF-I and IGF-II) are potent mitogens for some human breast cancer cell lines, and expression of IGF-II mRNA in the oestrogen receptor-positive (ER+) and oestradiol (E2) stimulated human breast cancer cell line T47D is increased by E2, suggesting a role for IGF......-II in the mitogenic response to E2. Very little information is available from the literature on the relation between growth inhibition by endocrine therapy and cellular production of IGF-II. Here we report on the effect of E2 and tamoxifen (TAM) on IGF-II mRNA and protein expression in the ER+T61 human...... breast cancer xenograft. Growth of the T61 tumour is inhibited by treatment with E2 and TAM. Ribonuclease (RNAse) protection assays with human- and mouse-specific IGF-II antisense probes were used to study the regulation of IGF-II mRNA by E2 and TAM in the tumour. IGF-II protein expression was studied by...

  16. Survival Analysis of Breast Cancer Subtypes in Spinal Metastases Patients

    DEFF Research Database (Denmark)

    Wang, Miao; Jensen, Anders Bonde; Morgen, Soeren Smith;

    2014-01-01

    downgraded from score "5" to "3" in Tokuhashi scoring system and from "slow growth" to "moderate growth" in Tomita scoring system. Spine surgeons should be critical before performing high-risk extensive surgery in patients with ER/HR (-) status, and especially, in those with triple-negative status. LEVEL OF......STUDY DESIGN: We conducted a retrospective cohort study of 151 patients with breast cancer spinal metastases. OBJECTIVE: To investigate the influence of breast cancer subtypes on survival duration of patients with breast cancer spinal metastases, and to aid spine surgeons in selecting treatments on...

  17. Breast cancer with inguinal node recurrence

    OpenAIRE

    Shikha Goyal; Tarun Puri; Pramod K Julka

    2015-01-01

    Surgery and irradiation for breast cancer may interfere with conventional pathways of spread, leading to bizarre patterns of dissemination through lymphatics or through hematogenous route. Lymphoscintigraphic studies may help identify nodal involvement. Other possible reasons could be occurrence of primary breast cancer in accessory breast tissue retained in the vulva following involution of milk line. We describe a case of triple negative breast cancer, who developed contralateral breast can...

  18. Breast Cancer Risk Prediction Models

    Science.gov (United States)

    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.

  19. DNA methylation markers for breast cancer prognosis

    OpenAIRE

    Dedeurwaerder, Sarah; Fuks, François

    2012-01-01

    Currently, most of the prognostic and predictive gene expression signatures emerging for breast cancer concern the tumor component. In Dedeurwaerder et al. we show that DNA methylation profiling of breast tumors is a particularly sensitive means of capturing features of the immune component of breast tumors. Most importantly, correlation is observed between T-cell marker genes and breast cancer clinical outcome.

  20. What Is Breast Cancer in Men?

    Science.gov (United States)

    ... the breast are glandular tissue (they make breast milk in women), so cancers starting in these areas are sometimes called adenocarcinomas. ... collections of cells that, in women, produce breast milk) and grows into the ... about 2% of male breast cancers. This is because men do not usually have ...

  1. A study on genetic variants of Fibroblast growth factor receptor 2 (FGFR2 and the risk of breast cancer from North India.

    Directory of Open Access Journals (Sweden)

    Sarah Siddiqui

    Full Text Available Genome-Wide Association Studies (GWAS have identified Fibroblast growth factor receptor 2 (FGFR2 as a candidate gene for breast cancer with single nucleotide polymorphisms (SNPs located in intron 2 region as the susceptibility loci strongly associated with the risk. However, replicate studies have often failed to extrapolate the association to diverse ethnic regions. This hints towards the existing heterogeneity among different populations, arising due to differential linkage disequilibrium (LD structures and frequencies of SNPs within the associated regions of the genome. It is therefore important to revisit the previously linked candidates in varied population groups to unravel the extent of heterogeneity. In an attempt to investigate the role of FGFR2 polymorphisms in susceptibility to the risk of breast cancer among North Indian women, we genotyped rs2981582, rs1219648, rs2981578 and rs7895676 polymorphisms in 368 breast cancer patients and 484 healthy controls by Polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP assay. We observed a statistically significant association with breast cancer risk for all the four genetic variants (P<0.05. In per-allele model for rs2981582, rs1219648, rs7895676 and in dominant model for rs2981578, association remained significant after bonferroni correction (P<0.0125. On performing stratified analysis, significant correlations with various clinicopathological as well as environmental and lifestyle characteristics were observed. It was evident that rs1219648 and rs2981578 interacted with exogenous hormone use and advanced clinical stage III (after Bonferroni correction, P<0.000694, respectively. Furthermore, combined analysis on these four loci revealed that compared to women with 0-1 risk loci, those with 2-4 risk loci had increased risk (OR = 1.645, 95%CI = 1.152-2.347, P = 0.006. In haplotype analysis, for rs2981578, rs2981582 and rs1219648, risk haplotype (GTG was

  2. THERAPEUTIC OPTIONS FOR BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Milena Georgescu

    2011-12-01

    Full Text Available Breast cancer remains a major public health problem, being the second cause of cancer death in women. There is a marked tendency to restrict the extension of surgical gesture, which directly leads to two different attitudes: radical surgery and conservative surgery, to which, at least in our country, there are still some delays. Prospective and retrospective studies have shown that, in 20 years, conservative and radical therapy had about the same rate of survival and disease-free interval, at least for stage I and II breast cancer, the only real counterargument against conservative surgery being that, in principle, the higher rate of recurrence local constraint can be solved by postoperative radiotherapy. Finally, the survival rate is the main parameter of evaluation, assessing the effectiveness of the treatment in breast cancer, and in all its other forms.

  3. The broad-spectrum metalloproteinase inhibitor BB-94 inhibits growth, HER3 and Erk activation in fulvestrant-resistant breast cancer cell lines

    DEFF Research Database (Denmark)

    Kirkegaard, Tove; Yde, Christina Westmose; Kveiborg, Marie; Lykkesfeldt, Anne E

    2014-01-01

    consequently increased cell growth. In this study, we investigated the importance of HER receptors, in particular HER3, and HER ligand shedding for growth and signaling in human MCF-7 breast cancer cells and MCF-7-derived sublines resistant to the antiestrogen fulvestrant. The HER3/HER4 ligand heregulin 1β...... induced phosphorylation of HER3, Akt and Erk, and partly rescued fulvestrant-inhibited growth of MCF-7 cells. HER3 ligands were found to be produced and shed from the fulvestrant-resistant cells as conditioned medium from fulvestrant-resistant MCF-7 cells induced phosphorylation of HER3 and Akt in MCF-7...... cells. This was prevented by treatment of resistant cells with the metalloproteinase inhibitor TAPI-2. Only the broad-spectrum metalloproteinase inhibitor BB-94, and not the more selective inhibitors GM6001 or TAPI-2, which inhibited shedding of the HER ligands produced by the fulvestrant...

  4. Aromatase Inhibitors and Other Compounds for Lowering Breast Cancer Risk

    Science.gov (United States)

    ... Cancer? Breast Cancer Colon/Rectum Cancer Lung Cancer Prostate Cancer Skin Cancer Show All Cancer Types News and Features Cancer Glossary ACS Bookstore Cancer Information Cancer Basics Cancer Prevention & Detection Signs & Symptoms of Cancer Treatments & Side Effects ...

  5. Do We Know What Causes Breast Cancer?

    Science.gov (United States)

    ... Next Topic Can breast cancer be prevented? Do we know what causes breast cancer? Many risk factors ... Genes have instructions for how our cells function. We usually look like our parents because they are ...

  6. Breast Cancer Prevention and Early Detection

    Science.gov (United States)

    ... saved articles window. My Saved Articles » My ACS » Breast Cancer Prevention and Early Detection Download Printable Version [PDF] » ( ... the factors that may affect your risk for breast cancer, and find out what you can do to ...

  7. Breast Cancer: Match of Her Life

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Breast Cancer The Match of Her Life Past Issues / Spring - ... Martina Navratilova stays strong in her battle against breast cancer and her work to help Americans live healthier, ...

  8. Breast Cancer and the Environment Research Program

    Science.gov (United States)

    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.

  9. Antiperspirants/Deodorants and Breast Cancer

    Science.gov (United States)

    ... Overview–for health professionals Research Antiperspirants/Deodorants and Breast Cancer On This Page Can antiperspirants or deodorants cause breast cancer? What do scientists know about the ingredients in ...

  10. Hormone Therapy for Breast Cancer in Men

    Science.gov (United States)

    ... Topic Targeted therapy for breast cancer in men Hormone therapy for breast cancer in men Hormone therapy ... fatigue, and pain at the injection site. Luteinizing hormone-releasing hormone (LHRH) analogs and anti-androgens LHRH ...

  11. Honoring Pioneers in Breast Cancer Research

    Science.gov (United States)

    ... Current Issue Past Issues Honoring Pioneers in Breast Cancer Research Past Issues / Spring 2007 Table of Contents For ... Distinguished Medical Service Award for their pioneering breast cancer research. Photo courtesy of Bill Branson, NIH In this ...

  12. Why Breast Cancer Survivors Should Exercise

    Science.gov (United States)

    ... fullstory_159781.html Why Breast Cancer Survivors Should Exercise Moderate physical activity can ease stress that impairs ... to memory problems among breast cancer survivors, but exercise can help, according to new research. "We found ...

  13. Higher vascular endothelial growth factor-C concentration in plasma is associated with increased forearm capillary filtration capacity in breast cancer-related lymphedema

    DEFF Research Database (Denmark)

    Jensen, Mads Radmer; Simonsen, Lene; Karlsmark, Tonny;

    2015-01-01

    Breast cancer-related lymphedema (BCRL) is a frequent, chronic and debilitating swelling that mainly affects the ipsilateral arm and develops as a complication to breast cancer treatment. The pathophysiology is elusive opposing development of means for prediction and treatment. We have earlier...

  14. Chapter 27 -- Breast Cancer Genomics, Section VI, Pathology and Biological Markers of Invasive Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Spellman, Paul T.; Heiser, Laura; Gray, Joe W.

    2009-06-18

    Breast cancer is predominantly a disease of the genome with cancers arising and progressing through accumulation of aberrations that alter the genome - by changing DNA sequence, copy number, and structure in ways that that contribute to diverse aspects of cancer pathophysiology. Classic examples of genomic events that contribute to breast cancer pathophysiology include inherited mutations in BRCA1, BRCA2, TP53, and CHK2 that contribute to the initiation of breast cancer, amplification of ERBB2 (formerly HER2) and mutations of elements of the PI3-kinase pathway that activate aspects of epidermal growth factor receptor (EGFR) signaling and deletion of CDKN2A/B that contributes to cell cycle deregulation and genome instability. It is now apparent that accumulation of these aberrations is a time-dependent process that accelerates with age. Although American women living to an age of 85 have a 1 in 8 chance of developing breast cancer, the incidence of cancer in women younger than 30 years is uncommon. This is consistent with a multistep cancer progression model whereby mutation and selection drive the tumor's development, analogous to traditional Darwinian evolution. In the case of cancer, the driving events are changes in sequence, copy number, and structure of DNA and alterations in chromatin structure or other epigenetic marks. Our understanding of the genetic, genomic, and epigenomic events that influence the development and progression of breast cancer is increasing at a remarkable rate through application of powerful analysis tools that enable genome-wide analysis of DNA sequence and structure, copy number, allelic loss, and epigenomic modification. Application of these techniques to elucidation of the nature and timing of these events is enriching our understanding of mechanisms that increase breast cancer susceptibility, enable tumor initiation and progression to metastatic disease, and determine therapeutic response or resistance. These studies also

  15. Role of RANKL/RANK in primary and secondary breast cancer

    OpenAIRE

    Yoneda, Toshiyuki; Tanaka, Soichi; Hata, Kenji

    2013-01-01

    Bone is one of the most preferential metastatic target sites of breast cancer. Bone possesses unique biological microenvironments in which various growth factors are stored and continuously released through osteoclastic bone resorption, providing fertile soil for circulating breast cancer cells. Bone-disseminated breast cancer cells in turn produce osteotropic cytokines which modulate bone environments. Under the influences of breast cancer-produced cytokines, osteoblasts express elevated lev...

  16. Nucleostemin expression in invasive breast cancer

    International Nuclear Information System (INIS)

    Recently, the cancer stem cell hypothesis has become widely accepted. Cancer stem cells are thought to possess the ability to undergo self-renewal and differentiation, similar to normal stem cells. Nucleostemin (NS), initially cloned from rat neural stem cells, binds to various proteins, including p53, in the nucleus and is thought to be a key molecule for stemness. NS is expressed in various types of cancers; therefore, its role in cancer pathogenesis is thought to be important. This study was conducted to clarify the clinicopathological and prognostic impact of NS in invasive breast cancers. The correlation between NS immunoreactivity and clinicopathological parameters was examined in 220 consecutive surgically resected invasive breast cancer tissue samples by using tissue microarrays. The presence of nuclear NS and p53 immunoreactivity in 10% or more of cancer cells was considered as a positive result. Among the 220 patients, 154 were hormone-receptor (HR)-positive, 22 HER2-positive/HR-negative, and 44 HR-negative/HER2-negative. One hundred and forty-two tumors (64.5%) showed NS positivity, and this positivity was significantly correlated with estrogen receptor (ER) (P = 0.050), human epidermal growth factor receptor 2 (HER2) (P = 0.021), and p53 (P = 0.031) positivity. The patients with NS-positive tumors showed significantly shorter disease-free survival than those with NS-negative tumors. Furthermore, the patient group with NS- and p53-positive tumors showed significantly poorer prognosis than other patient groups. Multivariate analysis showed that NS status was an independent prognostic indicator. NS may play a significant role in the determination of breast cancer progression in association with p53 alterations. The NS status of patients with luminal and HER2 type breast cancers may be a useful prognostic marker

  17. Dilemma of Pregnant Ladies with Breast Cancer

    OpenAIRE

    Zainur Rashid Z; S Sulaiha S A; Lew K G; Nurhana S

    2009-01-01

    Gestational breast cancer (GBC) or pregnancyassociatedbreast cancer was defined as breast cancerdiagnosed during pregnancy and within 1 year ofdelivery. Breast cancer is the second commonest cancerafter cervical seen in pregnancy and lactation.Nevertheless, the incidence is low and accounts forapproximately 1 in 3000 of pregnancies. A delay indiagnosis is common and 70% to 89% of patients withoperable primary lesions already have positive axillarylymph nodes. Breast cancer identified during p...

  18. Sexuality After Breast Cancer: Need for Guideline

    OpenAIRE

    Vaziri, Sh; Lotfi Kashani, F

    2012-01-01

    Background Clinical experiences have revealed that patients with breast cancer experience various sexual problems following their treatment. Breast cancer negatively impacts the sexual life of the afflicted couples, and as a traumatic event can influence women’s psychosexual functioning and intimate relationship. This review focuses on sexuality after breast cancer and on a growing need for bio-psycho-social guidelines for breast cancer treatment. Methods This study aims to review the literat...

  19. Energy Balance and Breast Cancer Risk

    OpenAIRE

    Malin, Alecia; Matthews, Charles E.; Shu, Xiao-Ou; Cai, Hui; Dai, Qi; Jin, Fan; Gao, Yu-Tang; Zheng, Wei

    2005-01-01

    We evaluated the hypothesis that a pattern of behavioral exposures indicating positive energy balance [i.e., less exercise/sport activity, high body mass index (BMI), or high energy intake] would be associated with an increased breast cancer risk in the Shanghai Breast Cancer Study, a population-based study of 1,459 incident breast cancer cases and 1,556 age frequency-matched controls. Participants completed in-person interviews that collected information on breast cancer risk factors, usual ...

  20. Physical activity and breast cancer survival

    OpenAIRE

    Ogunleye, Adeyemi A; Holmes, Michelle D.

    2009-01-01

    Physical activity improves quality of life after a breast cancer diagnosis, and a beneficial effect on survival would be particularly welcome. Four observational studies have now reported decreased total mortality among physically active women with breast cancer; the two largest have also reported decreased breast cancer specific mortality. The estrogen pathway and the insulin pathway are two potential mechanisms by which physical activity could affect breast cancer survival. Randomized trial...

  1. IMMUNOPHENOTYPIC CHARACTERISTICS OF INFLAMMATORY BREAST CANCER

    OpenAIRE

    A. I. Berishvili; N. N. Tupitsyn; K. P. Laktionov

    2014-01-01

    The investigation enrolled 31 patients with inflammatory breast cancer (IBC) treated at the N. N. Blokhin Cancer Research Center from 2006 to 2008. IBC is diagnosed on the basis of signs of rapid progression, such as localized or generalized breast induration, red- ness and edema. IBC accounts for less than 5% of all diagnosed breast cancers and is the most lethal form of primary breast cancer. We studied tumor markers of the immunophenotype of IBC and levels and subpopulations of immunocompe...

  2. Safety and Efficacy of Trastuzumab Emtansine in Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: a Meta-analysis.

    Science.gov (United States)

    Shen, Kai; Ma, Xuelei; Zhu, Chenjing; Wu, Xin; Jia, Hongyuan

    2016-01-01

    Advanced or metastatic breast cancer is an incurable disease with high mortality rate worldwide and about 20% of breast cancers overexpress and amplify the human epidermal growth factor receptor 2 (HER2). Achievements in targeted therapy have benefited people during the past decades. Trastuzumab emtansine (T-DM1), a novel antibody-drug conjugate playing a powerful role in anti-tumor activity, not only blocks the HER2 signaling pathways, but also disturbs the microtubule dynamics. To access the efficacy and safety of T-DM1, we analyzed 9 clinical trials on T-DM1. Results showed that fatigue (0.604, 95% CI 0.551, 0.654), nausea (0.450, 95% CI 0.365, 0.537), increased transaminases (0.425, 95% CI 0.353, 0.500) and thrombocytopenia (0.383, 95% CI 0.322, 0.448) occurred more frequently in participants with single T-DM1. In controlled trials, increased transaminases (OR = 4.040, 95% CI 1.429, 11.427), thrombocytopenia (OR = 8.500, 95% CI 3.964, 18.226) and fatigue (OR = 1.288, 95% CI 1.041, 1.593) were statistically significant. Only thrombocytopenia appeared as severe adverse event (grade ≥ 3) in single-arm and control-arm studies. Meanwhile, T-DM1 stabilized cancer and prolonged life with notable improved progression-free survival (PFS) and overall survival (OS). In conclusion, it is a safe and effective agent in advanced or metastatic breast cancer, but should be carefully applied on patients with severe hepatic and neurological disease. PMID:26979925

  3. Multicenter breast cancer collaborative registry.

    Science.gov (United States)

    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

  4. The role of vitamin D in breast cancer

    Directory of Open Access Journals (Sweden)

    Tu Tu Aung

    2011-12-01

    Full Text Available The biological role of vitamin D outside of calcium homeostasis is still under evaluation. The ability of vitamin D to inhibit cell proliferation and induce differentiation makes it a potential modifier of neoplastic transformation. Vitamin D affects the cell cycle, apoptosis, hormone receptors, angiogenesis, and hypoxia, all of which are related to the breast cancer growth, progression and metastasis. A large percentage of the industrial-world population is deficient in vitamin D. Epidemiological evidence suggests that vitamin D deficiency increases the risk of breast cancer. Vitamin D may have synergistic, additive, or antagonistic effects when combined with other therapeutic agents against breast cancer. Vitamin D appears to depress aromatase inhibitor by acting through cytochrome P 450. This evidence along with pre-clinical and clinical studies, justify the inclusion of vitamin D in future clinical trials related to breast cancer in order to determine its efficacy as a part of the breast cancer therapeutic armament.

  5. Breast and Ovarian Cancer and Family History Risk Categories

    Science.gov (United States)

    ... in one breast only) diagnosed after age 50 Grandmother with breast cancer diagnosed at age 75 Get ... breast cancer diagnosed at age 45 and paternal grandmother (father’s mother) with breast cancer diagnosed at age ...

  6. Dermatologic radiotherapy and breast cancer

    International Nuclear Information System (INIS)

    This study was set up to provide quantitative data to evaluate unsubstantiated claims that improper dermatologic radiation techniques may cause breast cancer. A thin mylar window ionization rate meter placed at the location of the right breast of an Alderson-RANDO anthropomorphic phantom was used to measure direct and scatter radiation reaching the female breast during radiotherapy of the facial region (as given for acne). The results indicate that scatter doses are very small; they are influenced by radiation quality and the use or nonuse of a treatment cone. Quantitative risk estimates show that the very small risk of breast cancer induction can be reduced even further by the use of proper radiation protection measures. (orig.)

  7. Minocycline Hydrochloride in Reducing Chemotherapy Induced Depression and Anxiety in Patients With Stage I-III Breast Cancer

    Science.gov (United States)

    2016-03-07

    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

  8. Fulvestrant and Palbociclib in Treating Older Patients With Hormone Responsive Breast Cancer That Cannot Be Removed by Surgery

    Science.gov (United States)

    2016-04-29

    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

  9. Screening for Breast Cancer: Staging and Treatment

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Screening For Breast Cancer Staging and Treatment Past Issues / Summer 2014 Table ... oncology nurse and a registered dietitian. Read More "Screening For Breast Cancer" Articles #BeBrave: A life-saving test / Breast Cancer ...

  10. Internet Use and Breast Cancer Survivors

    Science.gov (United States)

    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…

  11. Microfluidics:Rapid Diagnosis for Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Satvinder Panesar; Suresh Neethirajan

    2016-01-01

    Breast cancer affected 1.7 million people worldwide in 2012 and accounts for approximately 23.3% of all cancers diagnosed in women. The disease is characterized by a genetic mutation, either inherited or resulting from envi-ronmental factors, that causes uncontrollable cellular growth of breast tissue or adjacent tissues. Current means of diag-nosing this disease depend on the individual analyzing the results from bulky, highly technical, and expensive equipment that is not globally accessible. As a result, patients can go undiagnosed due to a lack of available equipment or be over-diagnosed due to human error. This review attempts to highlight current means of diagnosing breast cancer and critically analyze their effectiveness and usefulness in terms of patient survival. An alternative means based on microfluidics biomarker detection is then presented. This method can be considered as a primary screening tool for diagnosing breast cancer based on its robustness, high throughput, low energy requirements, and accessibility to the general public.

  12. Primary synchronous bilateral breast cancer

    Directory of Open Access Journals (Sweden)

    R Krishnappa

    2014-01-01

    Full Text Available Background: Primary synchronous bilateral breast cancer (PSBBC is a rare clinical entity. The reported incidence ranges between 0.3% and 12%. There are several controversial issues regarding PSBBC pertaining to the diagnostic criteria, nomenclature, and management policies. Materials and Methods: Fourteen cases of PSBBC treated between 2001 to 2010 at our institute were retrospectively analysed in regards to demographic data, management and follow up. Results: PSBBC constituted 0.19% of total breast cancer patients at our institute. Age ranged from 28 to 78 years. PSBBC were detected by clinical examination in eight cases and by mammography in six cases. Twelve patients underwent bilateral modified radical mastectomy, one had unilateral mastectomy on one side and breast conservation on the other side and one patient has bilateral breast conservation. Majority of patients belonged to stage 2 and stage 3. All patients were found to have invasive ductal carcinoma. Five cases were ER/PR positive and 8 patients were triple hormone receptor negative. Eight patients received unilateral and six received bilateral adjuvant radiotherapy. Nine patients received adjuvant chemotherapy. 5 patients received adjuvant hormonal therapy. Median follow up of patients was 15.4 months. Conclusion: PSBBC is a rare event warranting awareness and screening of the contralateral breast in patients with unilateral breast cancer. These patients require individualized treatment planning based on the tumor factors of the index lesion. Further multi institutional prospective studies are needed for adequate understanding of management of PSBBC.

  13. Breast Cancer Metastasis to the Stomach Resembling Early Gastric Cancer

    OpenAIRE

    Eo, Wan Kyu

    2008-01-01

    Breast cancer metastases to the stomach are infrequent, with an estimated incidence rate of approximately 0.3%. Gastric metastases usually are derived from lobular rather than from ductal breast cancer. The most frequent type of a breast cancer metastasis as seen on endoscopy to the stomach is linitis plastica; features of a metastatic lesion that resemble early gastric cancer (EGC) are extremely rare. In this report, we present a case of a breast cancer metastasis to the stomach from an infi...

  14. 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)

    Science.gov (United States)

    2016-08-24

    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

  15. Platycodin D inhibits migration, invasion, and growth of MDA-MB-231 human breast cancer cells via suppression of EGFR-mediated Akt and MAPK pathways.

    Science.gov (United States)

    Chun, Jaemoo; Kim, Yeong Shik

    2013-10-01

    Platycodin D (PD), an active triterpenoid saponin from Platycodon grandiflorum, has been known to inhibit the proliferation of a variety of cancer cells, but the effect of PD on the invasiveness of cancer cells is largely unknown. In this study, we first determined the molecular mechanism by which PD inhibits the migratory and invasive abilities of the highly metastatic MDA-MB-231 breast cancer cell line. We demonstrated that a non-cytotoxic concentration of PD markedly suppressed wound healing migration, invasion through the matrigel, and adhesion to an ECM-coated substrate in a dose-dependent manner. Moreover, PD inhibited cell invasion by reducing matrix metalloproteinase (MMP)-9 enzyme activity and mRNA expression. Western blot analysis indicated that PD potently suppressed the phosphorylation of extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK) as well as blocked the phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR signaling pathway. Furthermore, PD treatment inhibited the DNA binding activity of NF-κB, which is known to mediate the expression of epidermal growth factor receptor (EGFR), as observed by electrophoretic mobility shift assay. Specific mechanisms of action exerted by PD involved the downregulation of EGFR and the inhibition of EGF-induced activation of the EGFR, MAPK, and PI3K/Akt pathways. The in vivo studies showed that PD significantly inhibited the growth of MDA-MB-231 xenograft tumors in BALB/c nude mice. These results suggest that PD might be a potential therapeutic candidate for the treatment of breast cancer metastasis. PMID:23867902

  16. Insulin-Like Growth Factor-1 Inscribes a Gene Expression Profile for Angiogenic Factors and Cancer Progression in Breast Epithelial Cells

    Directory of Open Access Journals (Sweden)

    J.S. Oh

    2002-01-01

    Full Text Available Activation of the insulin-like growth factor-1 receptor (IGF-11R by IGF-1 is associated with the risk and progression of many types of cancer, although despite this it remains unclear how activated IGF-1 R contributes to cancer progression. In this study, gene expression changes elicited by IGF-1 were profiled in breast epithelial cells. We noted that many genes are functionally linked to cancer progression and angiogenesis. To validate some of the changes observed, the RNA and/or protein was confirmed for c-fos, cytochrome P4501Al, cytochrome P450 1131, interleukin-1 beta, fas ligand, vascular endothelial growth factor, and urokinase plasminogen activator. Nuclear proteins were also temporally monitored to address how gene expression changes were regulated. We found that IGF-1 stimulated the nuclear translocation of phosphorylated AKT, hypoxic-inducible factor-1 alpha, and phosphorylated cAMP-responsive element-binding protein, which correlated with temporal changes in gene expression. Next, the promoter regions of IGF-1-regulated genes were searched in silico. The promoters of genes that clustered together had similar regulatory regions. In summary, IGF-1 inscribes a gene expression profile relevant to cancer progression, and this study provides insight into the mechanism(s whereby some of these changes occur.

  17. How to target estrogen receptor-negative breast cancer?

    Science.gov (United States)

    Rochefort, H; Glondu, M; Sahla, M E; Platet, N; Garcia, M

    2003-06-01

    Estrogen receptor (ER)-positive breast cancers generally have a better prognosis and are often responsive to anti-estrogen therapy, which is the first example of a successful therapy targeted on a specific protein, the ER. Unfortunately ER-negative breast cancers are more aggressive and unresponsive to anti-estrogens. Other targeted therapies are thus urgently needed, based on breast cancer oncogene inhibition or suppressor gene activation as far as molecular studies have demonstrated the alteration of expression, or structure of these genes in human breast cancer. Using the MDA-MB.231 human breast cancer cell line as a model of ER-negative breast cancers, we are investigating two of these approaches in our laboratory. Our first approach was to transfect the ER or various ER-deleted variants into an ER-negative cell line in an attempt to recover anti-estrogen responsiveness. The unliganded receptor, and surprisingly estradiol, were both found to inhibit tumor growth and invasiveness in vitro and in vivo. The mechanisms of these inhibitions in ER-negative cancer cells are being studied, in an attempt to target the ER sequence responsible for such inhibition in these cancer cells. Another strategy is trying to inhibit the activity or expression of an oncogene specifically overexpressed in most breast cancers. This approach was recently shown by others to be efficient in breast cancer therapy with HER2-Neu oncogene amplification using Herceptin. Without excluding other molecular putative targets, we have focused our research on cathepsin D as a potential target, since it is often overexpressed in aggressive human breast cancers, including ER-negative tumors, and rarely associated with HER2-Neu amplification. Our first results obtained in vitro on cell lines and in vivo in tumor xenografts in nude mice, illustrate that the mode of action of cathepsin D in breast cancer is useful to guide the development of these therapies. In the past 20 years we have learned that the

  18. Period-2: a tumor suppressor gene in breast cancer.

    Science.gov (United States)

    Xiang, Shulin; Coffelt, Seth B; Mao, Lulu; Yuan, Lin; Cheng, Qi; Hill, Steven M

    2008-01-01

    Previous reports have suggested that the ablation of the Period 2 gene (Per 2) leads to enhanced development of lymphoma and leukemia in mice. Employing immunoblot analyses, we have demonstrated that PER 2 is endogenously expressed in human breast epithelial cell lines but is not expressed or is expressed at significantly reduced level in human breast cancer cell lines. Expression of PER 2 in MCF-7 breast cancer cells significantly inhibited the growth of MCF-7 human breast cancer cells, and, when PER 2 was co-expressed with the Crytochrome 2 (Cry 2) gene, an even greater growth-inhibitory effect was observed. The inhibitory effect of PER 2 on breast cancer cells was also demonstrated by its suppression of the anchorage-independent growth of MCF-7 cells as evidenced by the reduced number and size of colonies. A corresponding blockade of MCF-7 cells in the G1 phase of the cell cycle was also observed in response to the expression of PER 2 alone or in combination with CRY 2. Expression of PER 2 also induced apoptosis of MCF-7 breast cancer cells as demonstrated by an increase in PARP [poly (ADP-ribose) polymerase] cleavage. Finally, our studies demonstrate that PER 2 expression in MCF-7 breast cancer cells is associated with a significant decrease in the expression of cyclin D1 and an up-regulation of p53 levels. PMID:18334030

  19. Breast cancer. Selected legal issues.

    Science.gov (United States)

    Wynstra, N A

    1994-07-01

    Several legal and ethical issues may arise during the course of screening for and diagnosis and treatment of breast cancer. Among the most active legal areas are reimbursement for therapies deemed experimental by certain insurance companies, such as high dose chemotherapy/autologous bone marrow transplantation (HDCT/ABMT) and off-label drug use; these reimbursement issues are discussed. Legal issues in mammography screening and insurance coverage and legal issues relative to informed consent in breast cancer treatment also are discussed. PMID:8004625

  20. Breast cancer - background and overview

    International Nuclear Information System (INIS)

    This summary is to provide the reader with a brief overview of the key concepts relating to epidemiology and etiology; clinical presentation and patterns of spread; Canadian guidelines for management; prognosis; and current Canadian screening recommendations in the diagnosis and treatment of breast cancer. This information will enable the reader to have the appropriate background knowledge before delving into the subsequent articles in this special CJMRT breast cancer edition. A variety of references have been provided for readers who are interested in more than a skeleton version of the current literature. (author)

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

    Science.gov (United States)

    2016-05-04

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

  2. TNFα acting on TNFR1 promotes breast cancer growth via p42/P44 MAPK, JNK, Akt and NF-κB-dependent pathways

    International Nuclear Information System (INIS)

    Tumor necrosis factor α (TNFα) enhances proliferation of chemically-induced mammary tumors and of T47D human cell line through not fully understood pathways. Here, we explored the intracellular signaling pathways triggered by TNFα, the participation of TNFα receptor (TNFR) 1 and TNFR2 and the molecular mechanism leading to breast cancer growth. We demonstrate that TNFα induced proliferation of C4HD murine mammary tumor cells and of T47D cells through the activation of p42/p44 MAPK, JNK, PI3-K/Akt pathways and nuclear factor-kappaB (NF-κB) transcriptional activation. A TNFα-specific mutein selectively binding to TNFR1 induced p42/p44 MAPK, JNK, Akt activation, NF-κB transcriptional activation and cell proliferation, just like wild-type TNFα, while a mutein selective for TNFR2 induced only p42/p44 MAPK activation. Interestingly, blockage of TNFR1 or TNFR2 with specific antibodies was enough to impair TNFα signaling and biological effect. Moreover, in vivo TNFα administration supported C4HD tumor growth. We also demonstrated, for the first time, that injection of a selective inhibitor of NF-κB activity, Bay 11-7082, resulted in regression of TNFα-promoted tumor. Bay 11-7082 blocked TNFα capacity to induce cell proliferation and up-regulation of cyclin D1 and of Bcl-xLin vivo and in vitro. Our results reveal evidence for TNFα as a breast tumor promoter, and provide novel data for a future therapeutic approach using TNFα antagonists and NF-κB pharmacological inhibitors in established breast cancer treatment

  3. Breast cancer-related lymphedema: Symptoms, diagnosis, risk reduction, and management

    OpenAIRE

    Fu, Mei R.

    2014-01-01

    The global burden of breast cancer continues to increase largely because of the aging and growth of the world population. More than 1.38 million women worldwide were estimated to be diagnosed with breast cancer in 2008, accounting for 23% of all diagnosed cancers in women. Given that the 5-year survival rate for breast cancer is now 90%, experiencing breast cancer is ultimately about quality of life. Women treated for breast cancer are facing a life-time risk of developing lymphedema, a chron...

  4. Milk stimulates growth of prostate cancer cells in culture.

    Science.gov (United States)

    Tate, Patricia L; Bibb, Robert; Larcom, Lyndon L

    2011-11-01

    Concern has been expressed about the fact that cows' milk contains estrogens and could stimulate the growth of hormone-sensitive tumors. In this study, organic cows' milk and two commercial substitutes were digested in vitro and tested for their effects on the growth of cultures of prostate and breast cancer cells. Cows' milk stimulated the growth of LNCaP prostate cancer cells in each of 14 separate experiments, producing an average increase in growth rate of over 30%. In contrast, almond milk suppressed the growth of these cells by over 30%. Neither cows' milk nor almond milk affected the growth of MCF-7 breast cancer cells or AsPC-1 pancreatic cancer cells significantly. Soy milk increased the growth rate of the breast cancer cells. These data indicate that prostate and breast cancer patients should be cautioned about the possible promotional effects of commercial dairy products and their substitutes. PMID:22043817

  5. Breast Cancer Biology and Ethnic Disparities in Breast Cancer Mortality in New Zealand: A Cohort Study

    OpenAIRE

    Seneviratne, Sanjeewa; Lawrenson, Ross; Scott, Nina; Kim, Boa; Shirley, Rachel; Campbell, Ian

    2015-01-01

    Introduction Indigenous Māori women have a 60% higher breast cancer mortality rate compared with European women in New Zealand. We investigated differences in cancer biological characteristics and their impact on breast cancer mortality disparity between Māori and NZ European women. Materials and Methods Data on 2849 women with primary invasive breast cancers diagnosed between 1999 and 2012 were extracted from the Waikato Breast Cancer Register. Differences in distribution of cancer biologica...

  6. NUCKS overexpression in breast cancer

    Directory of Open Access Journals (Sweden)

    Kittas Christos

    2009-08-01

    Full Text Available Abstract Background NUCKS (Nuclear, Casein Kinase and Cyclin-dependent Kinase Substrate is a nuclear, DNA-binding and highly phosphorylated protein. A number of reports show that NUCKS is highly expressed on the level of mRNA in several human cancers, including breast cancer. In this work, NUCKS expression on both RNA and protein levels was studied in breast tissue biopsies consisted of invasive carcinomas, intraductal proliferative lesions, benign epithelial proliferations and fibroadenomas, as well as in primary cultures derived from the above biopsies. Specifically, in order to evaluate the level of NUCKS protein in correlation with the histopathological features of breast disease, immunohistochemistry was employed on paraffin sections of breast biopsies of the above types. In addition, NUCKS expression was studied by means of Reverse Transcription PCR (RT-PCR, real-time PCR (qRT-PCR and Western immunoblot analyses in the primary cell cultures developed from the same biopsies. Results The immunohistochemical Results showed intense NUCKS staining mostly in grade I and II breast carcinomas compared to normal tissues. Furthermore, NUCKS was moderate expressed in benign epithelial proliferations, such as adenosis and sclerosing adenosis, and highly expressed in intraductal lesions, specifically in ductal carcinomas in situ (DCIS. It is worth noting that all the fibroadenoma tissues examined were negative for NUCKS staining. RT-PCR and qRT-PCR showed an increase of NUCKS expression in cells derived from primary cultures of proliferative lesions and cancerous tissues compared to the ones derived from normal breast tissues and fibroadenomas. This increase was also confirmed by Western immunoblot analysis. Although NUCKS is a cell cycle related protein, its expression does not correlate with Ki67 expression, neither in tissue sections nor in primary cell cultures. Conclusion The results show overexpression of the NUCKS protein in a number of non

  7. HER-2 Positive Breast Cancer - a Mini-Review.

    Science.gov (United States)

    Asif, Hafiz Muhammad; Sultana, Sabira; Ahmed, Saeed; Akhtar, Naheed; Tariq, Muhammad

    2016-01-01

    Breast cancer is one of among all cancers with increased incidence, high mortality rate, and high economic and social costs. The the most common type of cancer among females worldwide, breast cancer is actually the uncontrolled proliferation of cells which attain malignancy. Recently it has shown that breast cancer contributes 11% among all types of cancer diagnosed globally on an annual basis and it is one of the leading causes of death among women. The human epidermal growth factor receptor 2 (HER-2) is a receptor tyrosine-protein kinase erbB-2 normally involved in the proliferation and division of breast cells. In some abnormal cases the HER2 gene does not work correctly and makes too many copies of itself. HER2-positive (HER2+) breast cancers constitute an aggressive type of breast cancer and tend to grow faster and are more likely to spread. However, therapies that specifically target HER2, such as Herceptin® (traztuzumab), are very effective. HER2 targeted therapies, has significantly improved the therapeutic outcome for patients with HER2 positive breast cancer. PMID:27221828

  8. Breast cancer epidemiology and risk factors

    International Nuclear Information System (INIS)

    Breast cancer is the most common malignancy among women in the Western society. Over the past decades it has become apparent that breast cancer incidence rates are increasing steadily, whereas the mortality rates for breast cancer have remained relatively constant. Information through the media on this rising number of cases has increased breast health awareness but has also introduced anxiety in the female population. This combination of factors has made the need for prevention of breast cancer an urgent matter. Breast cancer does not seem to be a single disease entity. A specific etiologic factor may therefore have more influence on one form may therefore have more influence on one form of breast cancer than another. So far though, as shown in their summary of current knowledge on established and dubious risk factors, no risk factors have been identified that can explain a major part of the incidence. Efforts to identify other ways for primary prevention have also been discouraging, even though breast cancer is one of the most investigated tumours world-wide. Thus, at this point i time, the most important strategy to reduce breast cancer mortality is early detection through individual counselling and organised breast screening programs. The recent isolation of breast cancer susceptibility genes may introduce new ways to reduce the risk of breast cancer in a small subset of women

  9. Ultrasound screening of contralateral breast after surgery for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seung Ja [Department of Radiology, Seoul Metropolitan Government Seoul National University, Boramae Medical Center (Korea, Republic of); Chung, Se-Yeong; Chang, Jung Min; Cho, Nariya [Department of Radiology, Seoul National University Hospital (Korea, Republic of); Han, Wonshik [Department of Surgery, Seoul National University Hospital (Korea, Republic of); Moon, Woo Kyung, E-mail: moonwk@snu.ac.kr [Department of Radiology, Seoul National University Hospital (Korea, Republic of)

    2015-01-15

    Highlights: • The addition of supplemental US to mammography depicted additional 5.0 cancers per 1000 postoperative women. • Positive biopsy rate of mammography-detected lesions was 66.7% (4 of 6) and that of US-detected lesions was 40.0% (6 of 15). • US can be helpful to detect mammographically occult breast cancer in the contralateral breast in women with previous history of cancer and dense breast. - Abstract: Objective: To determine whether supplemental screening ultrasound (US) to mammography could improve cancer detection rate of the contralateral breast in patients with a personal history of breast cancer and dense breasts. Materials and methods: During a one-year study period, 1314 screening patients with a personal history of breast cancer and dense breasts simultaneously underwent mammography and breast US. BI-RADS categories were given for mammography or US-detected lesions in the contralateral breast. The reference standard was histology and/or 1-year imaging follow-up, and the cancer rate according to BI-RADS categories and cancer detection rate and positive biopsy rate according to detection modality were analyzed. Results: Of 1314 patients, 84 patients (6.4%) were categorized as category 3 with one interval cancer and one cancer which was upgraded to category 4A after 6-month follow-up US (2.5% cancer rate, 95% CIs 1.5–9.1%). Fifteen patients (1.1%) had category 4A or 4B lesions in the contralateral breast. Four lesions were detected on mammography (two lesions were also visible on US) and 11 lesions were detected on US and 5 cancers were confirmed (33.3%, 95% CIs 15.0–58.5%). Six patients (0.5%) had category 4C lesions, 2 detected on mammography and 4 on US and 4 cancers were confirmed (66.7%, 95% CIs 29.6–90.8%). No lesions were categorized as category 5 in the contralateral breast. Cancer detection rate by mammography was 3.3 per 1000 patients and that by US was 5.0 per 1000 patients, therefore overall cancer detection rate by

  10. Ultrasound screening of contralateral breast after surgery for breast cancer

    International Nuclear Information System (INIS)

    Highlights: • The addition of supplemental US to mammography depicted additional 5.0 cancers per 1000 postoperative women. • Positive biopsy rate of mammography-detected lesions was 66.7% (4 of 6) and that of US-detected lesions was 40.0% (6 of 15). • US can be helpful to detect mammographically occult breast cancer in the contralateral breast in women with previous history of cancer and dense breast. - Abstract: Objective: To determine whether supplemental screening ultrasound (US) to mammography could improve cancer detection rate of the contralateral breast in patients with a personal history of breast cancer and dense breasts. Materials and methods: During a one-year study period, 1314 screening patients with a personal history of breast cancer and dense breasts simultaneously underwent mammography and breast US. BI-RADS categories were given for mammography or US-detected lesions in the contralateral breast. The reference standard was histology and/or 1-year imaging follow-up, and the cancer rate according to BI-RADS categories and cancer detection rate and positive biopsy rate according to detection modality were analyzed. Results: Of 1314 patients, 84 patients (6.4%) were categorized as category 3 with one interval cancer and one cancer which was upgraded to category 4A after 6-month follow-up US (2.5% cancer rate, 95% CIs 1.5–9.1%). Fifteen patients (1.1%) had category 4A or 4B lesions in the contralateral breast. Four lesions were detected on mammography (two lesions were also visible on US) and 11 lesions were detected on US and 5 cancers were confirmed (33.3%, 95% CIs 15.0–58.5%). Six patients (0.5%) had category 4C lesions, 2 detected on mammography and 4 on US and 4 cancers were confirmed (66.7%, 95% CIs 29.6–90.8%). No lesions were categorized as category 5 in the contralateral breast. Cancer detection rate by mammography was 3.3 per 1000 patients and that by US was 5.0 per 1000 patients, therefore overall cancer detection rate by

  11. Suppression of motor protein KIF3C expression inhibits tumor growth and metastasis in breast cancer by inhibiting TGF-β signaling.

    Science.gov (United States)

    Wang, Chengqin; Wang, Chenggang; Wei, Zhimin; Li, Yujun; Wang, Wenhong; Li, Xia; Zhao, Jing; Zhou, Xuan; Qu, Xun; Xiang, Fenggang

    2015-11-01

    Breast cancer is the most common cause of death among women. KIF3C, a member of kinesin superfamily, functions as a motor protein involved in axonal transport in neuronal cells. To explore the expression, regulation and mechanism of KIF3C in breast cancer, 4 breast cancer cell lines and 93 cases of primary breast cancer and paired adjacent tissues were examined. Immunohistochemistry, Real Time Polymerase Chain Reaction (RT-PCR), Western blot, flow cytometry, short hairpin RNA (shRNA) interference, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation techniques and xenograft mice model were used. We found that KIF3C was over-expressed in breast cancer tissues and such high KIF3C expression was also associated with tumor recurrence and lymph node metastasis. Silencing of KIF3C by shRNA inhibited epithelial-mesenchymal transition and metastasis by inhibiting TGF-β signaling and suppressed breast cancer cell proliferation through inducing G2/M phase arrest. The tumor size was smaller and the number of lung metastatic nodules was less in KIF3C depletion MDA-MB-231 cell xenograft mice than in negative control group. These results suggested that high expression of KIF3C in breast cancer may be associated with the tumor progression and metastasis. PMID:26272184

  12. Association of breast cancer risk loci with breast cancer survival

    NARCIS (Netherlands)

    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 eviden

  13. Involvement of 1,25D3-MARRS (membrane associated, rapid response steroid-binding), a novel vitamin D receptor, in growth inhibition of breast cancer cells

    International Nuclear Information System (INIS)

    In addition to classical roles in calcium homeostasis and bone development, 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] inhibits the growth of several cancer types, including breast cancer. Although cellular effects of 1,25(OH)2D3 traditionally have been attributed to activation of a nuclear vitamin D receptor (VDR), a novel receptor for 1,25(OH)2D3 called 1,25D3-MARRS (membrane-associated, rapid response steroid-binding) protein was identified recently. The purpose of this study was to determine if the level of 1,25D3-MARRS expression modulates 1,25(OH)2D3 activity in breast cancer cells. Relative levels of 1,25D3-MARRS protein in MCF-7, MDA MB 231, and MCF-10A cells were estimated by real-time RT-PCR and Western blotting. To determine if 1,25D3-MARRS receptor was involved in the growth inhibitory effects of 1,25(OH)2D3 in MCF-7 cells, a ribozyme construct designed to knock down 1,25D3-MARRS mRNA was stably transfected into MCF-7 cells. MCF-7 clones in which 1,25D3-MARRS receptor expression was reduced showed increased sensitivity to 1,25(OH)2D3 ( IC50 56 ± 24 nM) compared to controls (319 ± 181 nM; P 3-MARRS receptor lengthened the doubling time in transfectants treated with 1,25(OH)2D3. Knockdown of 1,25D3-MARRS receptor also increased the sensitivity of MCF-7 cells to the vitamin D analogs KH1060 and MC903, but not to unrelated agents (all-trans retinoic acid, paclitaxel, serum/glucose starvation, or the isoflavone, pomiferin). These results suggest that 1,25D3-MARRS receptor expression interferes with the growth inhibitory activity of 1,25(OH)2D3 in breast cancer cells, possibly through the nuclear VDR. Further research should examine the potential for pharmacological or natural agents that modify 1,25D3-MARRS expression or activity as anticancer agents.

  14. Breast cancer during pregnancy and lactation

    International Nuclear Information System (INIS)

    declared disease free 30 months later. The third case was a 32-year-old Saudi female who has been lactating for 5 months presented with a month history of a right breast lump. There was no history of nipple discharge or past history of any benign breast diseases. There was no family history of breast carcinoma. Clinically, there was an irregular right breast mass (5x3 cm) in the upper inner quadrant with palpable right axillary lymph nodes. She underwent right simple mastectomy and axillary clearance. Histology showed grade II infiltrating ductal carcinoma with 15/18 lymph nodes were positive. Postoperative adjuvant therapy was given but was lost to follow up 6 months after surgery. Chest wall radiation for cancers detected in the second or third trimester is delayed until after delivery to avoid fetal growth retardation and still births.3,4 The risk of abortion and fetal malformations is highest during embryogenesis in the first trimester and varies with the choice of chemotherapeutic agents. Recent evidence suggests that the risk of fetal malformations associated with administration of chemotherapeutic agents after the first trimester is not greater than the background control.6 The decision on postoperative adjuvant chemoradiation therapy in all the cases was made easy by the fact that CS was performed at the time of mastectomy in case one who gave birth to a healthy baby and that cases 2 and 3 were postpartum and were only lactating. Termination of pregnancy is considered in females presenting early in pregnancy with advanced or metastatic cancer necessitating chemotherapy and radiation

  15. PCNA immunostaining in breast cancer.

    Science.gov (United States)

    Cummings, M C; Furnival, C M; Parsons, P G; Townsend, E

    1993-08-01

    Expression of proliferating cell nuclear antigen (PCNA) has been shown to be of prognostic value in patients with certain types of cancer. The aim of this study was to determine if the abundance of PCNA is inversely correlated with survival of patients with breast cancer. Paraffin blocks were available from 68 patients, all of whom had been followed clinically for at least 5 years. Sections from 20 patients showed no reactivity to PCNA and were excluded from the study because it was not possible to distinguish between true negatives and false negatives (those due to poor fixation of the original specimens). The PCNA index (the number of stained cancer cells as a percentage of the total number of cancer cells present) was calculated for the remaining 48 patients. Results were analysed by Wilcoxon's rank sum test (two tailed) and Pearson's correlation coefficient. There was no statistical difference between the PCNA indices of those patients dead from their disease within 5 years of diagnosis compared with those alive and without signs of breast cancer at 5 years. There was also no correlation between PCNA index and size of the cancer, involvement of axillary lymph nodes, time to recurrence or time to death. There was, however, a significant correlation between PCNA index and histological grade (P = 0.029). It appears that PCNA staining of stored paraffin sections is of little prognostic value in patients with breast cancer. PMID:8101708

  16. Zinc isotopic compositions of breast cancer tissue.

    OpenAIRE

    Larner, F; Woodley, LN; Shousha, S; Moyes, A; Humphreys-Williams, E; Strekopytov, S; Halliday, AN; Rehkämper, M; Coombes, RC

    2015-01-01

    An early diagnostic biomarker for breast cancer is essential to improve outcome. High precision isotopic analysis, originating in Earth sciences, can detect very small shifts in metal pathways. For the first time, the natural intrinsic Zn isotopic compositions of various tissues in breast cancer patients and controls were determined. Breast cancer tumours were found to have a significantly lighter Zn isotopic composition than the blood, serum and healthy breast tissue in both groups. The Zn i...

  17. Elevated insulin receptor content in human breast cancer.

    OpenAIRE

    Papa, V.; Pezzino, V; Costantino, A.; Belfiore, A.; D. Giuffrida; Frittitta, L; Vannelli, G.B.; Brand, R.; Goldfine, I D; Vigneri, R

    1990-01-01

    The growth of breast cancer cells is under the regulation of hormones, growth factors, and their receptors. In the present study, we have employed a new, sensitive, and specific radioimmunoassay for the direct measurement of insulin receptors in surgical specimens of breast cancers. In 159 specimens the insulin receptor content was 6.15 +/- 3.69 ng/0.1 mg protein. This value was more than sixfold higher than the mean value found in both 27 normal breast tissues obtained at total mastectomy (0...

  18. Breast cancer: further metabolic-endocrine risk markers?

    OpenAIRE

    Stoll, B. A.

    1997-01-01

    There is evidence that increased oestrogen receptor (ER) expression in normal mammary epithelium may be a risk marker for the development of breast cancer. Insulin-like growth factor 1 (IGF1) is a potent inducer of mitosis and has been shown to synergize with oestrogen in stimulating the growth of human breast cancer in vitro. In these cells oestradiol has been shown to upregulate IGF type 1 receptor (IGFR), and recently a similar effect has been reported in normal human breast tissue xenogra...

  19. Breast Cancer Death Rates Down 34% Since 1990

    Science.gov (United States)

    ... Text Size News » Filed under: Breast Cancer Report: Breast Cancer Death Rates Down 34% Since 1990 Article date: ... American Cancer Society finds that death rates from breast cancer in the United States have dropped 34% since ...

  20. Prognostic value of breast cancer subtypes on breast cancer specific survival, distant metastases and local relapse rates in conservatively managed early stage breast cancer: a retrospective clinical study

    OpenAIRE

    Sanpaolo, Pietro; Barbieri, Viviana; Genovesi, Domenico

    2011-01-01

    International audience To ascertain if breast cancer subtypes had prognostic effect on breast cancer specific survival, distant metastases and local relapse rates in women affected by early stage breast cancer.