WorldWideScience

Sample records for non-malignant human breast

  1. Lipid peroxidation and antioxidants status in human malignant and non-malignant thyroid tumours.

    Science.gov (United States)

    Stanley, J A; Neelamohan, R; Suthagar, E; Vengatesh, G; Jayakumar, J; Chandrasekaran, M; Banu, S K; Aruldhas, M M

    2016-06-01

    Thyroid epithelial cells produce moderate amounts of reactive oxygen species that are physiologically required for thyroid hormone synthesis. Nevertheless, when they are produced in excessive amounts, they may become toxic. The present study is aimed to compare the lipid peroxidation (LPO), antioxidant enzymes - superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and non-protein thiols (reduced glutathione (GSH)) in human thyroid tissues with malignant and non-malignant disorders. The study used human thyroid tissues and blood samples from 157 women (147 diseased and 10 normal). Thyroid hormones, oxidative stress markers and antioxidants were estimated by standard methods. LPO significantly increased in most of the papillary thyroid carcinoma (PTC: 82.9%) and follicular thyroid adenoma (FTA: 72.9%) tissues, whilst in a majority of nodular goitre (69.2%) and Hashimoto's thyroiditis (HT: 73.7%) thyroid tissues, it remained unaltered. GSH increased in PTC (55.3%), remained unaltered in FTA (97.3%) and all other goiter samples studied. SOD increased in PTC (51.1%) and all other malignant thyroid tissues studied. CAT remained unaltered in PTC (95.7%), FTA (97.3%) and all other non-malignant samples (HT, MNG, TMNG) studied. GPx increased in PTC (63.8%), all other malignant thyroid tissues and remained unaltered in many of the FTA (91.9%) tissues and all other non-malignant samples (HT, MNG, TMNG) studied. In the case of non-malignant thyroid tumours, the oxidant-antioxidant balance was undisturbed, whilst in malignant tumours the balance was altered, and the change in r value observed in the LPO and SOD pairs between normal and PTC tissues and also in many pairs with multi-nodular goitre (MNG)/toxic MNG tissues may be used as a marker to differentiate/detect different malignant/non-malignant thyroid tumours. © The Author(s) 2015.

  2. Non-malignant disease mortality in meat workers: a model for studying the role of zoonotic transmissible agents in non-malignant chronic diseases in humans.

    Science.gov (United States)

    Johnson, E S; Zhou, Y; Sall, M; Faramawi, M El; Shah, N; Christopher, A; Lewis, N

    2007-12-01

    Current research efforts have mainly concentrated on evaluating the role of substances present in animal food in the aetiology of chronic diseases in humans, with relatively little attention given to evaluating the role of transmissible agents that are also present. Meat workers are exposed to a variety of transmissible agents present in food animals and their products. This study investigates mortality from non-malignant diseases in workers with these exposures. A cohort mortality study was conducted between 1949 and 1989, of 8520 meat workers in a union in Baltimore, Maryland, who worked in manufacturing plants where animals were killed or processed, and who had high exposures to transmissible agents. Mortality in meat workers was compared with that in a control group of 6081 workers in the same union, and also with the US general population. Risk was estimated by proportional mortality and standardised mortality ratios (SMRs) and relative SMR. A clear excess of mortality from septicaemia, subarachnoid haemorrhage, chronic nephritis, acute and subacute endocarditis, functional diseases of the heart, and decreased risk of mortality from pre-cerebral, cerebral artery stenosis were observed in meat workers when compared to the control group or to the US general population. The authors hypothesise that zoonotic transmissible agents present in food animals and their products may be responsible for the occurrence of some cases of circulatory, neurological and other diseases in meat workers, and possibly in the general population exposed to these agents.

  3. Dual-frequency electrical impedance mammography for the diagnosis of non-malignant breast disease

    International Nuclear Information System (INIS)

    Trokhanova, O V; Okhapkin, M B; Korjenevsky, A V

    2008-01-01

    Electrical impedance tomography (EIT) enables one to determine and visualize non-invasively the spatial distribution of the electrical properties of the tissues inside the body, thus providing valuable diagnostic information. The electrical impedance mammography (EIM) system is a specialized EIT system for diagnostics and imaging of the breast. While breast cancer is the main target for any investigation conducted in this area, the diagnosis of non-cancerous diseases is also very important because it opens the way to improve the quality of life for many women and it may also reduce the incidence of breast cancer through effective treatment of mastopathy. This paper presents the main results of a comprehensive examination of 166 women using four methods: multifrequency electrical impedance mammography, ultrasonic investigation, x-ray mammography and puncture biopsy. The objective of the investigation is to estimate the usefulness of multifrequency electrical impedance mammography for diagnosing dyshormonal mammary gland diseases. The results demonstrate the advantages of the multifrequency EIM method. In particular, dual-frequency electrical impedance mammography in contrast with the single-frequency variant enables one not only to diagnose mastopathy, but also allows accurate detection of its cystless form based on observation of the absence of any difference between average conductivity in both phases of the menstrual cycle. Because the cystless form of mastopathy is associated with a higher risk of cancer development, this method allows identification of a higher risk group of patients for more frequent investigations

  4. Ionizing radiation predisposes non-malignant human mammaryepithelial cells to undergo TGF beta-induced epithelial to mesenchymaltransition

    Energy Technology Data Exchange (ETDEWEB)

    Andarawewa, Kumari L.; Erickson, Anna C.; Chou, William S.; Costes, Sylvain; Gascard, Philippe; Mott, Joni D.; Bissell, Mina J.; Barcellos-Hoff, Mary Helen

    2007-04-06

    Transforming growth factor {beta}1 (TGF{beta}) is a tumor suppressor during the initial stage of tumorigenesis, but it can switch to a tumor promoter during neoplastic progression. Ionizing radiation (IR), both a carcinogen and a therapeutic agent, induces TGF{beta}, activation in vivo. We now show that IR sensitizes human mammary epithelial cells (HMEC) to undergo TGF{beta}-mediated epithelial to mesenchymal transition (EMT). Non-malignant HMEC (MCF10A, HMT3522 S1 and 184v) were irradiated with 2 Gy shortly after attachment in monolayer culture, or treated with a low concentration of TGF{beta} (0.4 ng/ml), or double-treated. All double-treated (IR+TGF{beta}) HMEC underwent a morphological shift from cuboidal to spindle-shaped. This phenotype was accompanied by decreased expression of epithelial markers E-cadherin, {beta}-catenin and ZO-1, remodeling of the actin cytoskeleton, and increased expression of mesenchymal markers N-cadherin, fibronectin and vimentin. Furthermore, double-treatment increased cell motility, promoted invasion and disrupted acinar morphogenesis of cells subsequently plated in Matrigel{trademark}. Neither radiation nor TGF{beta} alone elicited EMT, even though IR increased chronic TGF{beta} signaling and activity. Gene expression profiling revealed that double treated cells exhibit a specific 10-gene signature associated with Erk/MAPK signaling. We hypothesized that IR-induced MAPK activation primes non-malignant HMEC to undergo TGF{beta}-mediated EMT. Consistent with this, Erk phosphorylation were transiently induced by irradiation, persisted in irradiated cells treated with TGF{beta}, and treatment with U0126, a Mek inhibitor, blocked the EMT phenotype. Together, these data demonstrate that the interactions between radiation-induced signaling pathways elicit heritable phenotypes that could contribute to neoplastic progression.

  5. Expression of estrogen receptors in non-malignant mammary tissue modifies the association between insulin-like growth factor 1 and breast cancer risk.

    Science.gov (United States)

    Samoli, E; Lagiou, A; Zourna, P; Barbouni, A; Georgila, C; Tsikkinis, A; Vassilarou, D; Minaki, P; Sfikas, C; Spanos, E; Trichopoulos, D; Lagiou, P

    2015-04-01

    Several studies have reported that the insulin-like growth factor 1 (IGF-1) is positively associated with estrogen receptor-positive [ER(+)] breast cancer risk, whereas there is little or no association with respect to ER(-) breast cancer. All comparisons of ER(+) breast cancer cases, however, have been made versus healthy controls, for whom there is no information about the ER expression in their mammary gland. In the context of a case-control investigation conducted in Athens, Greece, we studied 102 women with incident ERα(+) breast cancer and compared their IGF-1 blood levels with those of 178 ERα(+) and 83 ERα(-) women with benign breast disease (BBD) who underwent biopsies in the context of their standard medical care. Data were analysed using multiple logistic regression and controlling for potential confounding variables. ERα(+) breast cancer patients had higher IGF-1 levels compared with women with BBD [odds ratio (OR) 1.36, 95% confidence interval (CI): 0.95-1.94, per 1 standard deviation (SD) increase in IGF-1 levels]. When ERα status of women with BBD was taken into account, the difference in IGF-1 levels between ERα(+) breast cancer patients and women with BBD was clearly driven by the comparison with BBD women who were ERα(+) (OR = 1.95, 95% CI: 1.31-2.89 per 1 SD increase in IGF-1 levels), whereas there was essentially no association with IGF-1 levels when ERα(+) breast cancer patients were compared with ERα(-) BBD women. These contrasts were particularly evident among post/peri-menopausal women. We found evidence in support of an interaction of IGF-1 with the expression of ERα in the non-malignant mammary tissue in the context of breast cancer pathogenesis. This is in line with previous evidence suggesting that IGF-1 increases the risk of ER(+) breast cancer. Published by Oxford University Press on behalf of the European Society for Medical Oncology 2014.

  6. Telomerase-immortalized non-malignant human prostate epithelial cells retain the properties of multipotent stem cells

    International Nuclear Information System (INIS)

    Li Hongzhen; Zhou Jianjun; Miki, Jun; Furusato, Bungo; Gu Yongpeng; Srivastava, Shiv; McLeod, David G.; Vogel, Jonathan C.; Rhim, Johng S.

    2008-01-01

    Understanding prostate stem cells may provide insight into the origin of prostate cancer. Primary cells have been cultured from human prostate tissue but they usually survive only 15-20 population doublings before undergoing senescence. We report here that RC-170N/h/clone 7 cells, a clonal cell line from hTERT-immortalized primary non-malignant tissue-derived human prostate epithelial cell line (RC170N/h), retain multipotent stem cell properties. The RC-170N/h/clone 7 cells expressed a human embryonic stem cell marker, Oct-4, and potential prostate epithelial stem cell markers, CD133, integrin α2β1 hi and CD44. The RC-170N/h/clone 7 cells proliferated in KGM and Dulbecco's Modified Eagle Medium with 10% fetal bovine serum and 5 μg/ml insulin (DMEM + 10% FBS + Ins.) medium, and differentiated into epithelial stem cells that expressed epithelial cell markers, including CK5/14, CD44, p63 and cytokeratin 18 (CK18); as well as the mesenchymal cell markers, vimentin, desmin; the neuron and neuroendocrine cell marker, chromogranin A. Furthermore the RC170 N/h/clone 7 cells differentiated into multi tissues when transplanted into the sub-renal capsule and subcutaneously of NOD-SCID mice. The results indicate that RC170N/h/clone 7 cells retain the properties of multipotent stem cells and will be useful as a novel cell model for studying the mechanisms of human prostate stem cell differentiation and transformation

  7. Combined cord blood and bone marrow transplantation from the same human leucocyte antigen-identical sibling donor for children with malignant and non-malignant diseases.

    Science.gov (United States)

    Tucunduva, Luciana; Volt, Fernanda; Cunha, Renato; Locatelli, Franco; Zecca, Marco; Yesilipek, Akif; Caniglia, Maurizio; Güngör, Tayfun; Aksoylar, Serap; Fagioli, Franca; Bertrand, Yves; Addari, Maria Carmen; de la Fuente, Josu; Winiarski, Jacek; Biondi, Andrea; Sengeloev, Henrik; Badell, Isabel; Mellgren, Karin; de Heredia, Cristina Díaz; Sedlacek, Petr; Vora, Ajay; Rocha, Vanderson; Ruggeri, Annalisa; Gluckman, Eliane

    2015-04-01

    Umbilical cord blood (UCB) from an human leucocyte antigen (HLA)-identical sibling can be used for transplantation of patients with malignant and non-malignant diseases. However, the low cellular content of most UCB units represents a limitation to this approach. An option to increase cell dose is to harvest bone marrow (BM) cells from the same donor and infuse them along with the UCB. We studied 156 children who received such a combined graft between 1992 and 2011. Median age was 7 years and 78% of patients (n = 122) were transplanted for non-malignant diseases, mainly haemoglobinopathies. Acute leukaemia (n = 26) was the most frequent malignant diagnosis. Most patients (91%) received myeloablative conditioning. Median donor age was 1·7 years, median infused nucleated cell dose was 24·4 × 10(7) /kg and median follow-up was 41 months. Sixty-days neutrophil recovery occurred in 96% of patients at a median of 17 d. The probabilities of grade-II-IV acute and chronic graft-versus-host disease (GVHD) were 19% and 10%, respectively. Four-year overall survival was 90% (68% malignant; 97% non-malignant diseases) with 3% probability of death. In conclusion, combined UCB and BM transplantation from an HLA-identical sibling donor is an effective treatment for children with malignant and non-malignant disorders with high overall survival and low incidence of GVHD. © 2014 John Wiley & Sons Ltd.

  8. Phenotypic characterization of telomerase-immortalized primary non-malignant and malignant tumor-derived human prostate epithelial cell lines

    International Nuclear Information System (INIS)

    Gu Yongpeng; Li Hongzhen; Miki, Jun; Kim, Kee-Hong; Furusato, Bungo; Sesterhenn, Isabell A.; Chu, Wei-Sing; McLeod, David G.; Srivastava, Shiv; Ewing, Charles M.; Isaacs, William B.; Rhim, Johng S.

    2006-01-01

    In vitro human prostate cell culture models are critical for clarifying the mechanism of prostate cancer progression and for testing preventive and therapeutic agents. Cell lines ideal for the study of human primary prostate tumors would be those derived from spontaneously immortalized tumor cells; unfortunately, explanted primary prostate cells survive only short-term in culture, and rarely immortalize spontaneously. Therefore, we recently have generated five immortal human prostate epithelial cell cultures derived from both the benign and malignant tissues of prostate cancer patients with telomerase, a gene that prevents cellular senescence. Examination of these cell lines for their morphologies and proliferative capacities, their abilities to grow in low serum, to respond to androgen stimulation, to grow above the agar layer, to form tumors in SCID mice, suggests that they may serve as valid, useful tools for the elucidation of early events in prostate tumorigenesis. Furthermore, the chromosome alterations observed in these immortalized cell lines expressing aspects of the malignant phenotypes imply that these cell lines accurately recapitulate the genetic composition of primary tumors. These novel in vitro models may offer unique models for the study of prostate carcinogenesis and also provide the means for testing both chemopreventive and chemotherapeutic agents

  9. Establishment of a normal-derived estrogen receptor-positive cell line comparable to the prevailing human breast cancer subtype

    DEFF Research Database (Denmark)

    Hopkinson, Branden Michael; Klitgaard, Marie Christine; Petersen, Ole William

    2017-01-01

    Understanding human cancer increasingly relies on insight gained from subtype specific comparisons between malignant and non-malignant cells. The most frequent subtype in breast cancer is the luminal. By far the most frequently used model for luminal breast cancer is the iconic estrogen receptor-...

  10. The hazards of using ionising radiation for non-malignant conditions - a case study

    International Nuclear Information System (INIS)

    Morton, Tracy

    1989-01-01

    A case study is presented in which a patient received low dose radiotherapy at seven months for a non-malignant cavernous haemangioma on the upper chest. She subsequently developed three separate malignancies before the age of 40 years: a thyroid carcinoma, a breast carcinoma and a basal cell carcinoma of the skin on the upper chest. This case illustrates the hazards of using ionizing radiation for the treatment of non-malignant conditions. (U.K.)

  11. The sensitivity of the human breast to cancer induction by ionizing radiation

    International Nuclear Information System (INIS)

    Mole, R.H.

    1978-01-01

    Available evidence for the induction of cancer in the human breast by small doses of radiation is reviewed. A comparison is made of risk estimates for the frequency of breast cancer in excess of controls, per rad of ionizing radiation, resulting from multiple fluoroscopy, radiotherapy of non-malignant diseases of the breast, or the exposure of Japanese bomb survivors. The significance of the age at exposure is discussed, and consideration is given to the application of the evidence to practical problems in radiography, radiotherapy, screening by mammography, and radiological protection for occupational exposure. (U.K.)

  12. Sensitivity of the human breast to cancer induction by ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Mole, R H [Medical Research Council, Harwell (UK). Radiobiological Research Unit

    1978-06-01

    Available evidence for the induction of cancer in the human breast by small doses of radiation is reviewed. A comparison is made of risk estimates for the frequency of breast cancer in excess of controls, per rad of ionizing radiation, resulting from multiple fluoroscopy, radiotherapy of non-malignant diseases of the breast, or the exposure of Japanese bomb survivors. The significance of the age at exposure is discussed, and consideration is given to the application of the evidence to practical problems in radiography, radiotherapy, screening by mammography, and radiological protection for occupational exposure.

  13. Aluminium and the human breast.

    Science.gov (United States)

    Darbre, P D

    2016-06-01

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

  14. Human Breast Cancer Histoid

    Science.gov (United States)

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

    2011-01-01

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

  15. Hypoxic conditions induce a cancer-like phenotype in human breast epithelial cells

    DEFF Research Database (Denmark)

    Vaapil, Marica; Helczynska, Karolina; Villadsen, René

    2012-01-01

    Solid tumors are less oxygenated than their tissue of origin. Low intra-tumor oxygen levels are associated with worse outcome, increased metastatic potential and immature phenotype in breast cancer. We have reported that tumor hypoxia correlates to low differentiation status in breast cancer. Less...... is known about effects of hypoxia on non-malignant cells. Here we address whether hypoxia influences the differentiation stage of non-malignant breast epithelial cells and potentially have bearing on early stages of tumorigenesis....

  16. Radiotherapy for non-malignant disorders

    International Nuclear Information System (INIS)

    Seegenschmiedt, Michael Heinrich; Makoski, Hans-Bruno; Trott, Klaus-Ruediger; Brady, Luther W.

    2008-01-01

    This volume discusses the general background, radiobiology, radiophysics and clinical applications of radiation therapy in the treatment of non-malignant diseases. Within 39 chapters, it documents the rationale and indications for the use of state-of-the-art radiotherapy for various non-malignant disorders of the CNS, head and neck, eye, skin and soft tissues, bone and joints, and the vascular system. In so doing, it draws attention to and elucidates the scope for application of radiotherapy beyond the treatment of malignancies. Both the risks and the benefits of such treatment are fully considered, the former ranging from minor clinical problems to life-threatening diseases. With the assistance of many tables and colored figures, the extensive data from clinical studies are presented in a well-structured and informative way. Each chapter concludes with a list of key points, allowing the reader to quickly comprehend the main facts. Since this approach offers an interdisciplinary perspective, this book will be of interest not only to radiotherapists but also to many other practitioners and medical specialists, for example orthopedists, surgeons, and ophthalmologists. (orig.)

  17. Adipokines in human breast milk.

    Science.gov (United States)

    Kratzsch, Juergen; Bae, Yoon Ju; Kiess, Wieland

    2018-01-01

    The review describes the molecular characteristics of so far detected breast milk adipokines and ranks their breast milk level compared to the respective levels in maternal and infant blood. Moreover, analytical knowledge for measurements of breast milk adipokines will be delineated. Next, we summarized data about two main potential influencing factors on adipokine concentration in breast milk, maternal weight and pasteurization of milk. Finally, associations between adipokines in breast milk and weight gain in infants as well as the putative mechanisms for effects of breast milk adipokines on food intake and weight gain in later life will debated. Our findings suggest that a source of adipokines in human breast milk cannot be uniformly defined. In dependence on the ratio between serum and breast milk levels the major quantity of these proteins may be derived from peripheral tissues, from the breast tissue itself or from both. Thus, leptin and in part adiponectin levels in breast milk are dependent on a plenty of influencing factors with an important relevance of maternal anthropometric characteristics There is some evidence that leptin, adiponectin and ghrelin levels in breast milk may be associated with growth gain of infants and even with increased risk for being overweight during infancy or childhood. We hypothesize that a dysregulation in adipokine homeostasis in early life could promote obesity and metabolic disturbance in later life. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Vitronectin in human breast carcinomas

    DEFF Research Database (Denmark)

    Aaboe, Mads; Offersen, Birgitte Vrou; Christensen, Anni

    2003-01-01

    We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast. Immunohistochemical analysis of carcinomas revealed a strong vitronectin accumulation in extracellular matrix (ECM) around some cancer cell clusters and in the subendothe......We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast. Immunohistochemical analysis of carcinomas revealed a strong vitronectin accumulation in extracellular matrix (ECM) around some cancer cell clusters...... and in the subendothelial area of some blood vessels. In normal tissue, vitronectin had a homogeneous periductal occurrence, with local accumulation much lower than that in the carcinomas. Using a new solid phase radioligand assay, the vitronectin concentrations of extracts of carcinomas and normal breast tissue were...... is not synthesised locally in breast tissue but derived by leakage from vessels, followed by extracellular accumulation in patterns distinctly different in carcinomas and normal tissue. The observation of a high vitronectin content in the carcinomas and its localisation in the tissue contributes to the clarification...

  19. The distribution of lectin receptor sites in human breast lesions.

    Science.gov (United States)

    Skutelsky, E; Hoenig, S; Griffel, B; Alroy, J

    1988-08-01

    Conflicting data regarding the status of A, B, H and T antigens in epithelium of normal, mastopathies, fibroadenomas and carcinomas of the breast stimulated us to re-examine the carbohydrate residues in these condition. Currently, we extended the number of carbohydrate residues studied by using ten different biotinylated lectins as probes and avidin-biotin-peroxidase complex (ABC) as a visualant. In addition, the pattern of lectin staining of cancerous cells in primary and metastatic sites was compared. In primary and metastatic breast carcinomas, lectin receptor sites were stained more intensely with Concanavalia ensiformi agglutinin (*Con A), Ricinus communis agglutinin-I (RCA-I) and wheat germ agglutinin (WGA), than in normal breast, in mastopathies or in fibroadenomas. Cryptic receptor sites for peanut agglutinin (PNA) were stained in all cases of breast carcinomas, while free PNA sites stained only in a few cases of well-differentiated carcinomas. Receptors sites for Ulex europaeus agglutinin-I (UEA-I) stained non-malignant epithelium of patients with blood group H but did not stain malignant cells. The results show significant differences in lectin-binding patterns and staining intensities between normal and non-malignant, and malignant epithelial breast cells. Furthermore, these results indicate that in malignant cells, there is an increased content of sialic acid-rich carbohydrates but not of asialylated glycoconjugates.

  20. Storage of Human Breast Milk

    Directory of Open Access Journals (Sweden)

    Gamze Can

    2007-10-01

    Full Text Available Storage of human breast milk by freezing or refrigeration of milk has been recommended especially at some social circumstances of most mothers who are regularly separated from their infants because of work. The greatest fear that has hindered the prospects of in - vitro storage of breast milk for any considerable period of time is the possibility of bacterial contamination and growth of infectious pathogens in the stored milk, there by rendering them unsafe for human consumption. The storage container can influence the cell content of milk, as the cells adhere to the walls of a glass container but not to polyethylene or polypropylene containers. Bacteriological examination of refrigerated milks has proven their safety for human consumption for even up to 72 h. For a storage over longer periods up to 1 month, freezing at - 20 0C could be recommended, but the most preferred method, especially for longer storage would be fresh freezing at - 70 0C, if affordable or available. The nutrient value of human milk is essentially unchanged, but the immunological properties are reduced by various storage techniques. Boiling and microwave radiation have not been recommended. [TAF Prev Med Bull 2007; 6(5.000: 375-379

  1. Human papilloma viruses (HPV and breast cancer.

    Directory of Open Access Journals (Sweden)

    James Sutherland Lawson

    2015-12-01

    Full Text Available Purpose: Human papillomaviruses (HPV may have a role in some breast cancers. The purpose of this study is to fill important gaps in the evidence. These gaps are: (i confirmation of the presence of high risk for cancer HPVs in breast cancers, (ii evidence of HPV infections in benign breast tissues prior to the development of HPV positive breast cancer in the same patients, (iii evidence that HPVs are biologically active and not harmless passengers in breast cancer.Methods: RNA-seq data from The Cancer Genome Atlas (TCGA was used to identify HPV RNA sequences in breast cancers. We also conducted a retrospective cohort study based on polymerase chain reaction (PCR analyses to identify HPVs in archival specimens from Australian women with benign breast biopsies who later developed breast cancer. To assess whether HPVs in breast cancer were biologically active, the expression of the oncogenic protein HPV E7 was assessed by immunohistochemistry (IHC.Results: Thirty (3.5% low risk and 20 (2.3% high risk HPV types were identified in 855 breast cancers from the TCGA data base. The high risk types were HPV 18 (48%, HPV 113 (24%, HPV 16 (10%, HPV 52 (10%. Data from the PCR cohort study, indicated that HPV type 18 was the most common type identified in breast cancer specimens (55% of 40 breast cancer specimens followed by HPV 16 (13%. The same HPV type was identified in both the benign and subsequent breast cancer in 15 patients. HPV E7 proteins were identified in 72% of benign breast specimens and 59% of invasive breast cancer specimens.Conclusions: There were 4 observations of particular interest: (i confirmation by both NGS and PCR of the presence of high risk HPV gene sequences in breast cancers, (ii a correlation between high risk HPV in benign breast specimens and subsequent HPV positive breast cancer in the same patient, (iii HPVs in breast cancer are likely to be biologically active (as shown by transcription of HPV DNA to RNA plus the expression of

  2. The Human Cell Surfaceome of Breast Tumors

    Science.gov (United States)

    da Cunha, Júlia Pinheiro Chagas; Galante, Pedro Alexandre Favoretto; de Souza, Jorge Estefano Santana; Pieprzyk, Martin; Carraro, Dirce Maria; Old, Lloyd J.; Camargo, Anamaria Aranha; de Souza, Sandro José

    2013-01-01

    Introduction. Cell surface proteins are ideal targets for cancer therapy and diagnosis. We have identified a set of more than 3700 genes that code for transmembrane proteins believed to be at human cell surface. Methods. We used a high-throuput qPCR system for the analysis of 573 cell surface protein-coding genes in 12 primary breast tumors, 8 breast cell lines, and 21 normal human tissues including breast. To better understand the role of these genes in breast tumors, we used a series of bioinformatics strategies to integrates different type, of the datasets, such as KEGG, protein-protein interaction databases, ONCOMINE, and data from, literature. Results. We found that at least 77 genes are overexpressed in breast primary tumors while at least 2 of them have also a restricted expression pattern in normal tissues. We found common signaling pathways that may be regulated in breast tumors through the overexpression of these cell surface protein-coding genes. Furthermore, a comparison was made between the genes found in this report and other genes associated with features clinically relevant for breast tumorigenesis. Conclusions. The expression profiling generated in this study, together with an integrative bioinformatics analysis, allowed us to identify putative targets for breast tumors. PMID:24195083

  3. A human breast cell model of pre-invasive to invasive transition

    Energy Technology Data Exchange (ETDEWEB)

    Bissell, Mina J; Rizki, Aylin; Weaver, Valerie M.; Lee, Sun-Young; Rozenberg, Gabriela I.; Chin, Koei; Myers, Connie A.; Bascom, Jamie L.; Mott, Joni D.; Semeiks, Jeremy R.; Grate, Leslie R.; Mian, I. Saira; Borowsky, Alexander D.; Jensen, Roy A.; Idowu, Michael O.; Chen, Fanqing; Chen, David J.; Petersen, Ole W.; Gray, Joe W.; Bissell, Mina J.

    2008-03-10

    A crucial step in human breast cancer progression is the acquisition of invasiveness. There is a distinct lack of human cell culture models to study the transition from pre-invasive to invasive phenotype as it may occur 'spontaneously' in vivo. To delineate molecular alterations important for this transition, we isolated human breast epithelial cell lines that showed partial loss of tissue polarity in three-dimensional reconstituted-basement membrane cultures. These cells remained non-invasive; however, unlike their non-malignant counterparts, they exhibited a high propensity to acquire invasiveness through basement membrane in culture. The genomic aberrations and gene expression profiles of the cells in this model showed a high degree of similarity to primary breast tumor profiles. The xenograft tumors formed by the cell lines in three different microenvironments in nude mice displayed metaplastic phenotypes, including squamous and basal characteristics, with invasive cells exhibiting features of higher grade tumors. To find functionally significant changes in transition from pre-invasive to invasive phenotype, we performed attribute profile clustering analysis on the list of genes differentially expressed between pre-invasive and invasive cells. We found integral membrane proteins, transcription factors, kinases, transport molecules, and chemokines to be highly represented. In addition, expression of matrix metalloproteinases MMP-9,-13,-15,-17 was up regulated in the invasive cells. Using siRNA based approaches, we found these MMPs to be required for the invasive phenotype. This model provides a new tool for dissection of mechanisms by which pre-invasive breast cells could acquire invasiveness in a metaplastic context.

  4. Epigenetic effects of human breast milk.

    Science.gov (United States)

    Verduci, Elvira; Banderali, Giuseppe; Barberi, Salvatore; Radaelli, Giovanni; Lops, Alessandra; Betti, Federica; Riva, Enrica; Giovannini, Marcello

    2014-04-24

    A current aim of nutrigenetics is to personalize nutritional practices according to genetic variations that influence the way of digestion and metabolism of nutrients introduced with the diet. Nutritional epigenetics concerns knowledge about the effects of nutrients on gene expression. Nutrition in early life or in critical periods of development, may have a role in modulating gene expression, and, therefore, have later effects on health. Human breast milk is well-known for its ability in preventing several acute and chronic diseases. Indeed, breastfed children may have lower risk of neonatal necrotizing enterocolitis, infectious diseases, and also of non-communicable diseases, such as obesity and related-disorders. Beneficial effects of human breast milk on health may be associated in part with its peculiar components, possible also via epigenetic processes. This paper discusses about presumed epigenetic effects of human breast milk and components. While evidence suggests that a direct relationship may exist of some components of human breast milk with epigenetic changes, the mechanisms involved are still unclear. Studies have to be conducted to clarify the actual role of human breast milk on genetic expression, in particular when linked to the risk of non-communicable diseases, to potentially benefit the infant's health and his later life.

  5. Epigenetic Effects of Human Breast Milk

    Directory of Open Access Journals (Sweden)

    Elvira Verduci

    2014-04-01

    Full Text Available A current aim of nutrigenetics is to personalize nutritional practices according to genetic variations that influence the way of digestion and metabolism of nutrients introduced with the diet. Nutritional epigenetics concerns knowledge about the effects of nutrients on gene expression. Nutrition in early life or in critical periods of development, may have a role in modulating gene expression, and, therefore, have later effects on health. Human breast milk is well-known for its ability in preventing several acute and chronic diseases. Indeed, breastfed children may have lower risk of neonatal necrotizing enterocolitis, infectious diseases, and also of non-communicable diseases, such as obesity and related-disorders. Beneficial effects of human breast milk on health may be associated in part with its peculiar components, possible also via epigenetic processes. This paper discusses about presumed epigenetic effects of human breast milk and components. While evidence suggests that a direct relationship may exist of some components of human breast milk with epigenetic changes, the mechanisms involved are still unclear. Studies have to be conducted to clarify the actual role of human breast milk on genetic expression, in particular when linked to the risk of non-communicable diseases, to potentially benefit the infant’s health and his later life.

  6. Stem cells in the human breast

    DEFF Research Database (Denmark)

    Petersen, Ole William; Polyak, Kornelia

    2010-01-01

    The origins of the epithelial cells participating in the development, tissue homeostasis, and cancer of the human breast are poorly understood. However, emerging evidence suggests a role for adult tissue-specific stem cells in these processes. In a hierarchical manner, these generate the two main...... mammary cell lineages, producing an increasing number of cells with distinct properties. Understanding the biological characteristics of human breast stem cells and their progeny is crucial in attempts to compare the features of normal stem cells and cancer precursor cells and distinguish these from...... nonprecursor cells and cells from the bulk of a tumor. A historical overview of research on human breast stem cells in primary tissue and in culture reveals the progress that has been made in this area, whereas a focus on the cell-of-origin and reprogramming that occurs during neoplastic conversion provides...

  7. Lactate dehydrogenase-B is silenced by promoter methylation in a high frequency of human breast cancers.

    Directory of Open Access Journals (Sweden)

    Nicola J Brown

    Full Text Available Under normoxia, non-malignant cells rely on oxidative phosphorylation for their ATP production, whereas cancer cells rely on Glycolysis; a phenomenon known as the Warburg effect. We aimed to elucidate the mechanisms contributing to the Warburg effect in human breast cancer.Lactate Dehydrogenase (LDH isoenzymes were profiled using zymography. LDH-B subunit expression was assessed by reverse transcription PCR in cells, and by Immunohistochemistry in breast tissues. LDH-B promoter methylation was assessed by sequencing bisulfite modified DNA.Absent or decreased expression of LDH isoenzymes 1-4, were seen in T-47D and MCF7 cells. Absence of LDH-B mRNA was seen in T-47D cells, and its expression was restored following treatment with the demethylating agent 5'Azacytadine. LDH-B promoter methylation was identified in T-47D and MCF7 cells, and in 25/25 cases of breast cancer tissues, but not in 5/5 cases of normal breast tissues. Absent immuno-expression of LDH-B protein (<10% cells stained, was seen in 23/26 (88% breast cancer cases, and in 4/8 cases of adjacent ductal carcinoma in situ lesions. Exposure of breast cancer cells to hypoxia (1% O(2, for 48 hours resulted in significant increases in lactate levels in both MCF7 (14.0 fold, p = 0.002, and T-47D cells (2.9 fold, p = 0.009, but not in MDA-MB-436 (-0.9 fold, p = 0.229, or MCF10AT (1.2 fold, p = 0.09 cells.Loss of LDH-B expression is an early and frequent event in human breast cancer occurring due to promoter methylation, and is likely to contribute to an enhanced glycolysis of cancer cells under hypoxia.

  8. Human breast milk immunology: a review.

    Science.gov (United States)

    Paramasivam, K; Michie, C; Opara, E; Jewell, A P

    2006-01-01

    Breast feeding has been shown to enhance the development of the immune system of the newborn as well as provide protection against enteric and respiratory infections. It has been suggested that implementation of breast feeding programs has the potential to save hundreds of thousands of lives worldwide. Human milk is a bodily fluid which, apart from being an excellent nutritional source for the growing infant, also contains a variety of immune components such as antibodies, growth factors, cytokines, antimicrobial compounds, and specific immune cells. These help to support the immature immune system of the newborn baby, and protect it against infectious risks during the postnatal period while its own immune system matures. This article reviews some of the factors in human breast milk that give it these important properties.

  9. Endocrine therapy of human breast cancer grown in nude mice

    DEFF Research Database (Denmark)

    Brünner, N; Osborne, C K; Spang-Thomsen, M

    1987-01-01

    mice bearing transplanted human breast tumors have been proposed as such a model. This review therefore discusses the use of the athymic nude mouse model of the study of human breast cancer biology, and focuses on four subjects: 1. biological characteristics of heterotransplanted breast tumors; 2...

  10. Cloning of Novel Oncogenes Involved in Human Breast Cancer

    National Research Council Canada - National Science Library

    Clark, Geoffrey

    1998-01-01

    .... In order to identify genes which may play a role in breast cancer we have begun a process of manufacturing cDNA expression libraries derived from human breast tumor cell lines in retroviral vectors...

  11. Chemical Biomarkers of Human Breast Milk Pollution

    Directory of Open Access Journals (Sweden)

    Benedetta Marchi

    2008-01-01

    Full Text Available Human milk is, without question, the best source of nutrition for infants containing the optimal balance of fats, carbohydrates and proteins for developing babies. Breastfeeding provides a range of benefits for growth, immunity and development building a powerful bond between mother and her child. Recognition of the manifold benefits of breast milk has led to the adoption of breast-feeding policies by numerous health and professional organizations such as the World Health Organization and American Academy of Pediatrics.In industrially developed as well as in developing nations, human milk contamination by toxic chemicals such as heavy metals, dioxins and organohalogen compounds, however, is widespread and is the consequence of decades of inadequately controlled pollution. Through breastfeeding, the mother may transfer to the suckling infant potentially toxic chemicals to which the mother has previously been exposed.In the present review, environmental exposure, acquisition and current levels of old and emerging classes of breast milk pollutants are systematically presented. Although scientific evidences indicated that the advantages of breast-feeding outweigh any risks from contaminants, it is important to identify contaminant trends, to locate disproportionately exposed populations, and to take public health measures to improve chemical BM pollution as possible.

  12. Defining the cellular precursors to human breast cancer

    Science.gov (United States)

    Keller, Patricia J.; Arendt, Lisa M.; Skibinski, Adam; Logvinenko, Tanya; Klebba, Ina; Dong, Shumin; Smith, Avi E.; Prat, Aleix; Perou, Charles M.; Gilmore, Hannah; Schnitt, Stuart; Naber, Stephen P.; Garlick, Jonathan A.; Kuperwasser, Charlotte

    2012-01-01

    Human breast cancers are broadly classified based on their gene-expression profiles into luminal- and basal-type tumors. These two major tumor subtypes express markers corresponding to the major differentiation states of epithelial cells in the breast: luminal (EpCAM+) and basal/myoepithelial (CD10+). However, there are also rare types of breast cancers, such as metaplastic carcinomas, where tumor cells exhibit features of alternate cell types that no longer resemble breast epithelium. Until now, it has been difficult to identify the cell type(s) in the human breast that gives rise to these various forms of breast cancer. Here we report that transformation of EpCAM+ epithelial cells results in the formation of common forms of human breast cancer, including estrogen receptor-positive and estrogen receptor-negative tumors with luminal and basal-like characteristics, respectively, whereas transformation of CD10+ cells results in the development of rare metaplastic tumors reminiscent of the claudin-low subtype. We also demonstrate the existence of CD10+ breast cells with metaplastic traits that can give rise to skin and epidermal tissues. Furthermore, we show that the development of metaplastic breast cancer is attributable, in part, to the transformation of these metaplastic breast epithelial cells. These findings identify normal cellular precursors to human breast cancers and reveal the existence of a population of cells with epidermal progenitor activity within adult human breast tissues. PMID:21940501

  13. A prototypical non-malignant epithelial model to study genome dynamics and concurrently monitor micro-RNAs and proteins in situ during oncogene-induced senescence

    DEFF Research Database (Denmark)

    Komseli, Eirini Stavroula; Pateras, Ioannis S.; Krejsgaard, Thorbjørn

    2018-01-01

    limitations achieving for the first time simultaneous detection of both a micro-RNA and a protein in the biological context of cellular senescence, utilizing the new commercially available SenTraGorTM compound. The method was applied in a prototypical human non-malignant epithelial model of oncogene...

  14. Cell membrane softening in human breast and cervical cancer cells

    Science.gov (United States)

    Händel, Chris; Schmidt, B. U. Sebastian; Schiller, Jürgen; Dietrich, Undine; Möhn, Till; Kießling, Tobias R.; Pawlizak, Steve; Fritsch, Anatol W.; Horn, Lars-Christian; Briest, Susanne; Höckel, Michael; Zink, Mareike; Käs, Josef A.

    2015-08-01

    Biomechanical properties are key to many cellular functions such as cell division and cell motility and thus are crucial in the development and understanding of several diseases, for instance cancer. The mechanics of the cellular cytoskeleton have been extensively characterized in cells and artificial systems. The rigidity of the plasma membrane, with the exception of red blood cells, is unknown and membrane rigidity measurements only exist for vesicles composed of a few synthetic lipids. In this study, thermal fluctuations of giant plasma membrane vesicles (GPMVs) directly derived from the plasma membranes of primary breast and cervical cells, as well as breast cell lines, are analyzed. Cell blebs or GPMVs were studied via thermal membrane fluctuations and mass spectrometry. It will be shown that cancer cell membranes are significantly softer than their non-malignant counterparts. This can be attributed to a loss of fluid raft forming lipids in malignant cells. These results indicate that the reduction of membrane rigidity promotes aggressive blebbing motion in invasive cancer cells.

  15. Polarized spectral features of human breast tissues through wavelet ...

    Indian Academy of Sciences (India)

    Abstract. Fluorescence characteristics of human breast tissues are investigated through wavelet transform and principal component analysis (PCA). Wavelet transform of polar- ized fluorescence spectra of human breast tissues is found to localize spectral features that can reliably differentiate different tissue types.

  16. Human Papilloma Viruses and Breast Cancer – Assessment of Causality

    Science.gov (United States)

    Lawson, James Sutherland; Glenn, Wendy K.; Whitaker, Noel James

    2016-01-01

    High risk human papilloma viruses (HPVs) may have a causal role in some breast cancers. Case–control studies, conducted in many different countries, consistently indicate that HPVs are more frequently present in breast cancers as compared to benign breast and normal breast controls (odds ratio 4.02). The assessment of causality of HPVs in breast cancer is difficult because (i) the HPV viral load is extremely low, (ii) HPV infections are common but HPV associated breast cancers are uncommon, and (iii) HPV infections may precede the development of breast and other cancers by years or even decades. Further, HPV oncogenesis can be indirect. Despite these difficulties, the emergence of new evidence has made the assessment of HPV causality, in breast cancer, a practical proposition. With one exception, the evidence meets all the conventional criteria for a causal role of HPVs in breast cancer. The exception is “specificity.” HPVs are ubiquitous, which is the exact opposite of specificity. An additional reservation is that the prevalence of breast cancer is not increased in immunocompromised patients as is the case with respect to HPV-associated cervical cancer. This indicates that HPVs may have an indirect causal influence in breast cancer. Based on the overall evidence, high-risk HPVs may have a causal role in some breast cancers. PMID:27747193

  17. Human Papilloma Viruses and Breast Cancer - Assessment of Causality.

    Science.gov (United States)

    Lawson, James Sutherland; Glenn, Wendy K; Whitaker, Noel James

    2016-01-01

    High risk human papilloma viruses (HPVs) may have a causal role in some breast cancers. Case-control studies, conducted in many different countries, consistently indicate that HPVs are more frequently present in breast cancers as compared to benign breast and normal breast controls (odds ratio 4.02). The assessment of causality of HPVs in breast cancer is difficult because (i) the HPV viral load is extremely low, (ii) HPV infections are common but HPV associated breast cancers are uncommon, and (iii) HPV infections may precede the development of breast and other cancers by years or even decades. Further, HPV oncogenesis can be indirect. Despite these difficulties, the emergence of new evidence has made the assessment of HPV causality, in breast cancer, a practical proposition. With one exception, the evidence meets all the conventional criteria for a causal role of HPVs in breast cancer. The exception is "specificity." HPVs are ubiquitous, which is the exact opposite of specificity. An additional reservation is that the prevalence of breast cancer is not increased in immunocompromised patients as is the case with respect to HPV-associated cervical cancer. This indicates that HPVs may have an indirect causal influence in breast cancer. Based on the overall evidence, high-risk HPVs may have a causal role in some breast cancers.

  18. Maintenance of prolactin receptors in human breast cancer

    International Nuclear Information System (INIS)

    Ben-David, M.; Dror, Y.; Biran, S.

    1981-01-01

    Breast tissue specimens of 110 women with various stages of breast cancer were tested in vitro to determine their specific binding sites for human prolactin. In contrast to the case of steroid receptors, binding sites for prolactin were found in the vast majority of breast cancer tissue. Distribution profiles giving amount of prolactin receptor and their affinity coefficients were found to be similar in the tissues of women whose ages, hormonal status, or stage of breast cancer varied. These findings show that in contrast to steroid receptors, human breast cancer tissue maintains binding sites for prolactin. The findings also indicate that there may be a higher dependency of breast cancer on prolactin than on steroids. Clinical trials must be carried out to determine the role of ''positive'' prolactin receptors in prognosis and prediction of response to future hormone therapy. (author)

  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. Comparison of breast cancer mucin (BCM) and CA 15-3 in human breast cancer

    NARCIS (Netherlands)

    Garcia, M.B.; Blankenstein, M.A.; Wall, E. van der; Nortier, J.W.R.; Schornagel, J.H.; Thijssen, J.H.H.

    1990-01-01

    The Breast Cancer Mucin (BCM) enzyme immunoassay utilizes two monoclonal antibodies (Mab), M85/34 and F36/22, for the identification of a mucin-like glycoprotein in serum of breast cancer patients. We have compared BCM with CA 15-3, another member of the human mammary epithelial antigen

  1. Identification of hormonal receptors in human breast cancer

    International Nuclear Information System (INIS)

    Rosa Pascual, M.; Lage, A.; Diaz, J.W.; Moreno, L.; Marta Diaz, T.

    1981-01-01

    The experience in the implementation of a technique for determining hormono-dependence of human breast cancer is presented. The results found with the use of the technique in 50 patients with malignant breast cancer treated at IOR are examined and discussed. (author)

  2. Smoking history, nicotine dependence and opioid use in patients with chronic non-malignant pain

    DEFF Research Database (Denmark)

    Plesner, K; Jensen, H I; Højsted, J

    2016-01-01

    doses than never smokers and former smokers not using nicotine. CONCLUSIONS: The study supports previous evidence that smoking is associated with chronic pain. Our data suggest that information about use of nicotine substitution in chronic non-malignant patients are relevant both in a clinical setting......BACKGROUND: Previous studies have demonstrated a positive association between smoking and addiction to opioids in patients with chronic non-malignant pain. This could be explained by a susceptibility in some patients to develop addiction. Another explanation could be that nicotine influences both...... pain and the opioid system. The objective of the study was to investigate whether smoking, former smoking ± nicotine use and nicotine dependence in patients with chronic non-malignant pain were associated with opioid use and addiction to opioids. METHODS: The study was a cross-sectional study carried...

  3. Breast abscess as a complication of human brucellosis.

    Science.gov (United States)

    Gurleyik, Emin

    2006-01-01

    Breast abscess caused by human brucellosis is extremely rare. A 46-year-old woman received the diagnosis of brucellosis with positive serologic tests. Two weeks after the onset of symptoms, the case was complicated by vertebral (L5-S1) abscess which was treated by surgical drainage. One month after the diagnosis of brucellosis, the patient noticed a mass in her left breast. Breast palpation revealed a painless, mobile, round mass that was hypoechoic on ultrasound imaging. Purulent material was obtained by needle aspiration. Besides treatment of the breast abscess by needle aspiration, brucellosis was successfully controlled by prolonged antimicrobial treatment.

  4. EXPRESSION AND SIGNIFICANCE OF ERK PROTEIN IN HUMAN BREAST CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    张秀梅; 李柏林; 宋敏; 宋继谒

    2004-01-01

    Objective: To investigate the expression of ERK and p-ERK protein in human breast cancer and their corresponding tissue, to assess the significance of ERK signal pathway in tumorigenesis and progression of breast carcinoma. Methods: 40 breast cancer cases were used in S-P immunohistochemistry technique and Western Blot study. Results: The expression of ERK1, ERK2, and p- ERK protein levels increased remarkably in breast cancer tissues in comparison to normal tissues (P<0.01). The expression was upregulated by 1.32-, 1.53-and 4.27-fold, respectively. The overexpressions of ERK1, ERK2, and p- ERK proteins were obviously correlated with clinical stage of breast cancer. Protein levels of ERK and p-ERK were higher in stage III patients than in stage I and stage II patients (P<0.05). These proteins were strongly related with axillary lymph node metastasis of breast cancer, but not correlated with histopathological type and status of ER and PR of breast cancer. Expression of ERK1, and ERK2, protein showed a positive linear correlation. Conclusion: ERK signal transduction pathway is a key factor during human breast tumorigenesis and breast cancer progression.

  5. Economic burden of non-malignant blood disorders across Europe: a population-based cost study.

    Science.gov (United States)

    Luengo-Fernandez, Ramon; Burns, Richeal; Leal, Jose

    2016-08-01

    Blood disorders comprise a wide range of diseases including anaemia, malignant blood disorders, and haemorrhagic disorders. Although they are a common cause of disease, no systematic cost-of-illness studies have been done to assess the economic effect of non-malignant blood disorders in Europe. We aimed to assess the economic burden of non-malignant blood disorders across the 28 countries of the European Union (EU), Iceland, Norway, and Switzerland. Non-malignant blood disorder-related costs (WHO International Classification of Diseases, 10th revision [ICD] D50-89) were estimated for 28 EU countries, Iceland, Norway, and Switzerland for 2012. Country-specific costs were estimated with aggregate data on morbidity, mortality, and health-care resource use obtained from international and national sources. Health-care costs were estimated from expenditure on primary care, outpatient care, emergency care, hospital inpatient care, and drugs. Costs of informal care and productivity losses due to morbidity and early death were also included. To these costs we added those due to malignant blood disorders (ICD-10 C81-96 and D47) as estimated in a Burns and colleagues' companion Article to obtain the total costs of blood disorders. Non-malignant disorders of the blood cost the 31 European countries €11 billion in 2012. Health-care costs accounted for €8 billion (75% of total costs), productivity losses for €2 billion (19%), and informal care for less than €1 billion (6%). Averaged across the European population studied, non-malignant disorders of the blood represented an annual health-care cost of €159 per ten citizens. Combining malignant and non-malignant blood disorders, the total cost of blood disorders was €23 billion in 2012. Our study highlights the economic burden that non-malignant blood disorders place on European health-care systems and societies. Our study also shows that blood disorder costs were evenly distributed between malignant and non-malignant

  6. Induction of apoptosis in human breast adenocarcinoma MCF-7 ...

    African Journals Online (AJOL)

    Induction of apoptosis in human breast adenocarcinoma MCF-7 cells by tannic acid and resveratrol. Ahu Soyocak, Didem Turgut Cosan, Ayse Basaran, Hasan Veysi Gunes, Irfan Degirmenci, Fezan Sahin Mutlu ...

  7. Evaluation of chemopreventive and cytotoxic effect of lemon seed extracts on human breast cancer (MCF-7) cells.

    Science.gov (United States)

    Kim, Jinhee; Jayaprakasha, Guddadarangavvanahally K; Uckoo, Ram M; Patil, Bhimanagouda S

    2012-02-01

    Extracts from lemon seed were investigated for the radical scavenging activity and apoptotic effects in human breast adenocarcinoma (MCF-7) cells and non-malignant breast (MCF-12F) cells for the first time. Defatted seed powder was successively extracted with ethyl acetate (EtOAc), acetone, methanol (MeOH), and MeOH:water (80:20). The chemical constituents were identified and quantified by LC-MS and HPLC analysis, respectively. The highest radical scavenging activity of 62.2% and 91.3% was exhibited by MeOH:water (80:20) at 833μg/mL in 1,1-diphenyl-2-picryl hydrazyl (DPPH) and 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS(+)), respectively. In addition, the MeOH:water (80:20) extract showed the highest (29.1%, Pwater (80:20) extract induced DNA fragmentation and poly(ADP-ribose) polymerase (PARP) cleavage. Increased levels of Bax and cytosolic cytochrome C and decreased levels of Bcl2 were also observed in MeOH:water (80:20) treated MCF-7 cells. In conclusion, the MeOH:water (80:20) extract from lemon seed has potent antioxidant activity and induces apoptosis in MCF-7 cells, leading to the inhibition of proliferation. These results suggest that aglycones and glucosides of the limonoids and flavonoid present in MeOH:water (80:20) extract may potentially serve as a chemopreventive agent for breast cancer. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. The physiology of the normal human breast: an exploratory study.

    Science.gov (United States)

    Mills, Dixie; Gordon, Eva J; Casano, Ashley; Lahti, Sarah Michelle; Nguyen, Tinh; Preston, Alex; Tondre, Julie; Wu, Kuan; Yanase, Tiffany; Chan, Henry; Chia, David; Esfandiari, Mahtash; Himmel, Tiffany; Love, Susan M

    2011-12-01

    The physiology of the nonlactating human breast likely plays a key role in factors that contribute to the etiology of breast cancer and other breast conditions. Although there has been extensive research into the physiology of lactation, few reports explore the physiology of the resting mammary gland, including mechanisms by which compounds such as hormones, drugs, and potential carcinogens enter the breast ducts. The purpose of this study was to explore transport of exogenous drugs into ductal fluid in nonlactating women and determine if their concentrations in the fluid are similar to those observed in the breast milk of lactating women. We selected two compounds that have been well characterized during lactation, caffeine and cimetidine. Caffeine passively diffuses into breast milk, but cimetidine is actively transported and concentrated in breast milk. After ingestion of caffeine and cimetidine, 14 nonlactating subjects had blood drawn and underwent ductal lavage at five time points over 12 h to measure drug levels in the fluid and blood. The concentrations of both caffeine and cimetidine in lavage fluid were substantially less than those observed in breast milk. Our results support recent evidence that the cimetidine transporter is not expressed in the nonlactating mammary gland, and highlight intriguing differences in the physiology and molecular transport of the lactating and nonlactating breast. The findings of this exploratory study warrant further exploration into the physiology of the nonlactating mammary gland to elucidate factors involved in disease initiation and progression.

  9. The role of tumor necrosis factor alpha in differentiation between malignant and non malignant pleural effusion

    Directory of Open Access Journals (Sweden)

    Heba M. Atef

    2016-07-01

    Conclusion: Pleural fluid level of TNF-α can be used in differentiating malignant from non malignant effusion. Also levels of TNF-α in the serum and pleural fluid could be useful as a complementary marker in the differential diagnosis of two most common types of exudates (tuberculous and malignant.

  10. Rhein Induces Apoptosis in Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ching-Yao Chang

    2012-01-01

    Full Text Available Human breast cancers cells overexpressing HER2/neu are more aggressive tumors with poor prognosis, and resistance to chemotherapy. This study investigates antiproliferation effects of anthraquinone derivatives of rhubarb root on human breast cancer cells. Of 7 anthraquinone derivatives, only rhein showed antiproliferative and apoptotic effects on both HER2-overexpressing MCF-7 (MCF-7/HER2 and control vector MCF-7 (MCF-7/VEC cells. Rhein induced dose- and time-dependent manners increase in caspase-9-mediated apoptosis correlating with activation of ROS-mediated activation of NF-κB- and p53-signaling pathways in both cell types. Therefore, this study highlighted rhein as processing anti-proliferative activity against HER2 overexpression or HER2-basal expression in breast cancer cells and playing important roles in apoptotic induction of human breast cancer cells.

  11. Infrared absorption of human breast tissues in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Liu Chenglin [Department of Physics, Surface Physics Laboratory (National Key laboratory), Synchrotron Radiation Research Center, Fudan University, Shanghai 200433 (China); Physics Department of Yancheng Teachers' College, Yancheng 224002 (China); Zhang Yuan [Department of Physics, Surface Physics Laboratory (National Key laboratory), Synchrotron Radiation Research Center, Fudan University, Shanghai 200433 (China); Yan Xiaohui [Department of Physics, Surface Physics Laboratory (National Key laboratory), Synchrotron Radiation Research Center, Fudan University, Shanghai 200433 (China); Zhang Xinyi [Department of Physics, Surface Physics Laboratory (National Key laboratory), Synchrotron Radiation Research Center, Fudan University, Shanghai 200433 (China) and Shanghai Research Center of Acupuncture and Meridian, Pudong, Shanghai 201203 (China)]. E-mail: xy-zhang@fudan.edu.cn; Li Chengxiang [National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei 230029 (China); Yang Wentao [Cancer Hospital, Medical Center, Fudan University, Shanghai 200032 (China); Shi Daren [Cancer Hospital, Medical Center, Fudan University, Shanghai 200032 (China)

    2006-07-15

    The spectral characteristics of human breast tissues in normal status and during different cancerous stages have been investigated by synchrotron radiation based Fourier transform infrared (SR-FTIR) absorption spectroscopy. Thanks to the excellent synchrotron radiation infrared (IR) source, higher resolving power is achieved in SR-FTIR absorption spectra than in conventional IR absorption measurements. Obvious variations in IR absorption spectrum of breast tissues were found as they change from healthy to diseased, or say in progression to cancer. On the other hand, some specific absorption peaks were found in breast cancer tissues by SR-FTIR spectroscopic methods. These spectral characteristics of breast tissue may help us in early diagnosis of breast cancer.

  12. ANALYSES ON DIFFERENTIALLY EXPRESSED GENES ASSOCIATED WITH HUMAN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    MENG Xu-li; DING Xiao-wen; XU Xiao-hong

    2006-01-01

    Objective: To investigate the molecular etiology of breast cancer by way of studying the differential expression and initial function of the related genes in the occurrence and development of breast cancer. Methods: Two hundred and eighty-eight human tumor related genes were chosen for preparation of the oligochips probe. mRNA was extracted from 16 breast cancer tissues and the corresponding normal breast tissues, and cDNA probe was prepared through reverse-transcription and hybridized with the gene chip. A laser focused fluorescent scanner was used to scan the chip. The different gene expressions were thereafter automatically compared and analyzed between the two sample groups. Cy3/Cy5>3.5 meant significant up-regulation. Cy3/Cy5<0.25 meant significant down-regulation. Results: The comparison between the breast cancer tissues and their corresponding normal tissues showed that 84 genes had differential expression in the Chip. Among the differently expressed genes, there were 4 genes with significant down-regulation and 6 with significant up-regulation. Compared with normal breast tissues, differentially expressed genes did partially exist in the breast cancer tissues. Conclusion: Changes in multi-gene expression regulations take place during the occurrence and development of breast cancer; and the research on related genes can help understanding the mechanism of tumor occurrence.

  13. Protein Kinases in Human Breast Carcinoma

    National Research Council Canada - National Science Library

    Cane, William

    1998-01-01

    .... Rak is a novel nuclear tyrosine that our group has identified in breast cancer tissues and cell lines that has structural homology to the Src tyrosine kinase, with SH2 and SH3 domains at its amino terminus...

  14. Cdx2 Polymorphism Affects the Activities of Vitamin D Receptor in Human Breast Cancer Cell Lines and Human Breast Carcinomas

    Science.gov (United States)

    Di Benedetto, Anna; Korita, Etleva; Goeman, Frauke; Sacconi, Andrea; Biagioni, Francesca; Blandino, Giovanni; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Falvo, Elisabetta

    2015-01-01

    Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D) and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative). These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression. PMID:25849303

  15. Cdx2 polymorphism affects the activities of vitamin D receptor in human breast cancer cell lines and human breast carcinomas.

    Directory of Open Access Journals (Sweden)

    Claudio Pulito

    Full Text Available Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR. It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954 human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative. These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression.

  16. Human breast tissue disposition and bioactivity of limonene in women with early stage breast cancer

    Science.gov (United States)

    Miller, Jessica A.; Lang, Julie E.; Ley, Michele; Nagle, Ray; Hsu, Chiu-Hsieh; Thompson, Patricia A; Cordova, Catherine; Waer, Amy; Chow, H.-H. Sherry

    2013-01-01

    Limonene is a bioactive food component found in citrus peel oil that has demonstrated chemopreventive and chemotherapeutic activities in preclinical studies. We conducted an open label pilot clinical study to determine the human breast tissue disposition of limonene and its associated bioactivity. We recruited forty-three women with newly diagnosed operable breast cancer electing to undergo surgical excision to take 2 grams of limonene daily for 2 – 6 weeks before surgery. Blood and breast tissue were collected to determine drug/metabolite concentrations and limonene-induced changes in systemic and tissue biomarkers of breast cancer risk or carcinogenesis. Limonene was found to preferentially concentrate in the breast tissue, reaching high tissue concentration (mean=41.3 μg/g tissue) while the major active circulating metabolite, perillic acid, did not concentrate in the breast tissue. Limonene intervention resulted in a 22% reduction in cyclin D1 expression (P=0.002) in tumor tissue but minimal changes in tissue Ki67 and cleaved caspase 3 expression. No significant changes in serum leptin, adiponectin, TGF-β1, IGFBP-3 and IL-6 levels were observed following limonene intervention. There was a small but statistically significant post-intervention increase in IGF-1 levels. We conclude that limonene distributed extensively to human breast tissue and reduced breast tumor cyclin D1 expression that may lead to cell cycle arrest and reduced cell proliferation. Further placebo-controlled clinical trials and translational research are warranted to establish limonene’s role for breast cancer prevention or treatment. PMID:23554130

  17. Human breast tissue disposition and bioactivity of limonene in women with early-stage breast cancer.

    Science.gov (United States)

    Miller, Jessica A; Lang, Julie E; Ley, Michele; Nagle, Ray; Hsu, Chiu-Hsieh; Thompson, Patricia A; Cordova, Catherine; Waer, Amy; Chow, H-H Sherry

    2013-06-01

    Limonene is a bioactive food component found in citrus peel oil that has shown chemopreventive and chemotherapeutic activities in preclinical studies. We conducted an open-label pilot clinical study to determine the human breast tissue disposition of limonene and its associated bioactivity. We recruited 43 women with newly diagnosed operable breast cancer electing to undergo surgical excision to take 2 grams of limonene daily for two to six weeks before surgery. Blood and breast tissue were collected to determine drug/metabolite concentrations and limonene-induced changes in systemic and tissue biomarkers of breast cancer risk or carcinogenesis. Limonene was found to preferentially concentrate in the breast tissue, reaching high tissue concentration (mean = 41.3 μg/g tissue), whereas the major active circulating metabolite, perillic acid, did not concentrate in the breast tissue. Limonene intervention resulted in a 22% reduction in cyclin D1 expression (P = 0.002) in tumor tissue but minimal changes in tissue Ki67 and cleaved caspase-3 expression. No significant changes in serum leptin, adiponectin, TGF-β1, insulin-like growth factor binding protein-3 (IGFBP-3), and interleukin-6 (IL-6) levels were observed following limonene intervention. There was a small but statistically significant postintervention increase in insulin-like growth factor I (IGF-I) levels. We conclude that limonene distributed extensively to human breast tissue and reduced breast tumor cyclin D1 expression that may lead to cell-cycle arrest and reduced cell proliferation. Furthermore, placebo-controlled clinical trials and translational research are warranted to establish limonene's role for breast cancer prevention or treatment.

  18. Hydroxytyrosol Protects against Oxidative DNA Damage in Human Breast Cells

    Directory of Open Access Journals (Sweden)

    José J. Gaforio

    2011-10-01

    Full Text Available Over recent years, several studies have related olive oil ingestion to a low incidence of several diseases, including breast cancer. Hydroxytyrosol and tyrosol are two of the major phenols present in virgin olive oils. Despite the fact that they have been linked to cancer prevention, there is no evidence that clarifies their effect in human breast tumor and non-tumor cells. In the present work, we present hydroxytyrosol and tyrosol’s effects in human breast cell lines. Our results show that hydroxytyrosol acts as a more efficient free radical scavenger than tyrosol, but both fail to affect cell proliferation rates, cell cycle profile or cell apoptosis in human mammary epithelial cells (MCF10A or breast cancer cells (MDA-MB-231 and MCF7. We found that hydroxytyrosol decreases the intracellular reactive oxygen species (ROS level in MCF10A cells but not in MCF7 or MDA-MB-231 cells while very high amounts of tyrosol is needed to decrease the ROS level in MCF10A cells. Interestingly, hydroxytyrosol prevents oxidative DNA damage in the three breast cell lines. Therefore, our data suggest that simple phenol hydroxytyrosol could contribute to a lower incidence of breast cancer in populations that consume virgin olive oil due to its antioxidant activity and its protection against oxidative DNA damage in mammary cells.

  19. Clinicopathological significance of PTPN12 expression in human breast cancer

    International Nuclear Information System (INIS)

    Yuan, Xunyi; Yuan, Zhentao; Jiang, Dandan; Li, Funian

    2012-01-01

    Protein tyrosine phosphatase non-receptor type 12 (PTPN12) is a recently identified tumor suppressor gene (TSG) that is frequently compromised in human triple-negative breast cancer. In the present study, we investigated the expression of PTPN12 protein by patients with breast cancer in a Chinese population and the relationship between PTPN12 expression levels and patient clinicopathological features and prognosis. Additionally, we explored the underlying down-regulation mechanism from the perspective of an epigenetic alteration. We examined PTPN12 mRNA expression in five breast cancer cell lines using semi-quantitative reverse-transcription PCR, and detected PTPN12 protein expression using immunohistochemistry in 150 primary invasive breast cancer cases and paired adjacent non-tumor tissues. Methylation-specific PCR was performed to analyze the promoter CpG island methylation status of PTPN12. PTPN12 was significantly down-regulated in breast cancer cases (48/150) compared to adjacent noncancerous tissues (17/150; P < 0.05). Furthermore, low expression of PTPN12 showed a significant positive correlation with tumor size (P = 0.047), lymph node metastasis (P = 0.001), distant metastasis (P = 0.009), histological grade (P = 0.012), and survival time (P = 0.019). Additionally, promoter CpG island hypermethylation occurs more frequently in breast cancer cases and breast cancer cell lines with low PTPN12 expression. Our findings suggest that PTPN12 is potentially a methylation-silenced TSG for breast cancer that may play an important role in breast carcinogenesis and could potentially serve as an independent prognostic factor for invasive breast cancer patients

  20. Development of realistic physical breast phantoms matched to virtual breast phantoms based on human subject data

    International Nuclear Information System (INIS)

    Kiarashi, Nooshin; Nolte, Adam C.; Sturgeon, Gregory M.; Ghate, Sujata V.; Segars, William P.; Nolte, Loren W.; Samei, Ehsan

    2015-01-01

    Purpose: Physical phantoms are essential for the development, optimization, and evaluation of x-ray breast imaging systems. Recognizing the major effect of anatomy on image quality and clinical performance, such phantoms should ideally reflect the three-dimensional structure of the human breast. Currently, there is no commercially available three-dimensional physical breast phantom that is anthropomorphic. The authors present the development of a new suite of physical breast phantoms based on human data. Methods: The phantoms were designed to match the extended cardiac-torso virtual breast phantoms that were based on dedicated breast computed tomography images of human subjects. The phantoms were fabricated by high-resolution multimaterial additive manufacturing (3D printing) technology. The glandular equivalency of the photopolymer materials was measured relative to breast tissue-equivalent plastic materials. Based on the current state-of-the-art in the technology and available materials, two variations were fabricated. The first was a dual-material phantom, the Doublet. Fibroglandular tissue and skin were represented by the most radiographically dense material available; adipose tissue was represented by the least radiographically dense material. The second variation, the Singlet, was fabricated with a single material to represent fibroglandular tissue and skin. It was subsequently filled with adipose-equivalent materials including oil, beeswax, and permanent urethane-based polymer. Simulated microcalcification clusters were further included in the phantoms via crushed eggshells. The phantoms were imaged and characterized visually and quantitatively. Results: The mammographic projections and tomosynthesis reconstructed images of the fabricated phantoms yielded realistic breast background. The mammograms of the phantoms demonstrated close correlation with simulated mammographic projection images of the corresponding virtual phantoms. Furthermore, power

  1. Development of realistic physical breast phantoms matched to virtual breast phantoms based on human subject data

    Energy Technology Data Exchange (ETDEWEB)

    Kiarashi, Nooshin [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 and Department of Electrical and Computer Engineering, Duke University, Durham, North Carolina 27708 (United States); Nolte, Adam C. [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 and Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708 (United States); Sturgeon, Gregory M.; Ghate, Sujata V. [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 (United States); Segars, William P. [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 and Medical Physics Graduate Program, Duke University, Durham, North Carolina 27708 (United States); Nolte, Loren W. [Department of Electrical and Computer Engineering, Duke University, Durham, North Carolina 27708 and Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708 (United States); Samei, Ehsan [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 (United States); Department of Electrical and Computer Engineering, Duke University, Durham, North Carolina 27708 (United States); Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708 (United States); Medical Physics Graduate Program, Duke University, Durham, North Carolina 27708 (United States); Department of Physics, Duke University, Durham, North Carolina 27708 (United States); and others

    2015-07-15

    Purpose: Physical phantoms are essential for the development, optimization, and evaluation of x-ray breast imaging systems. Recognizing the major effect of anatomy on image quality and clinical performance, such phantoms should ideally reflect the three-dimensional structure of the human breast. Currently, there is no commercially available three-dimensional physical breast phantom that is anthropomorphic. The authors present the development of a new suite of physical breast phantoms based on human data. Methods: The phantoms were designed to match the extended cardiac-torso virtual breast phantoms that were based on dedicated breast computed tomography images of human subjects. The phantoms were fabricated by high-resolution multimaterial additive manufacturing (3D printing) technology. The glandular equivalency of the photopolymer materials was measured relative to breast tissue-equivalent plastic materials. Based on the current state-of-the-art in the technology and available materials, two variations were fabricated. The first was a dual-material phantom, the Doublet. Fibroglandular tissue and skin were represented by the most radiographically dense material available; adipose tissue was represented by the least radiographically dense material. The second variation, the Singlet, was fabricated with a single material to represent fibroglandular tissue and skin. It was subsequently filled with adipose-equivalent materials including oil, beeswax, and permanent urethane-based polymer. Simulated microcalcification clusters were further included in the phantoms via crushed eggshells. The phantoms were imaged and characterized visually and quantitatively. Results: The mammographic projections and tomosynthesis reconstructed images of the fabricated phantoms yielded realistic breast background. The mammograms of the phantoms demonstrated close correlation with simulated mammographic projection images of the corresponding virtual phantoms. Furthermore, power

  2. Health care costs, work productivity and activity impairment in non-malignant chronic pain patients

    DEFF Research Database (Denmark)

    Kronborg, Christian; Handberg, Gitte; Axelsen, Flemming

    2009-01-01

    This study explores the costs of non-malignant chronic pain in patients awaiting treatment in a multidisciplinary pain clinic in a hospital setting. Health care costs due to chronic pain are particular high during the first year after pain onset, and remain high compared with health care costs be...... before pain onset. The majority of chronic pain patients incur the costs of alternative treatments. Chronic pain causes production losses at work, as well as impairment of non-work activities.......This study explores the costs of non-malignant chronic pain in patients awaiting treatment in a multidisciplinary pain clinic in a hospital setting. Health care costs due to chronic pain are particular high during the first year after pain onset, and remain high compared with health care costs...

  3. Extracellular vesicle-mediated phenotype switching in malignant and non-malignant colon cells

    International Nuclear Information System (INIS)

    Mulvey, Hillary E.; Chang, Audrey; Adler, Jason; Del Tatto, Michael; Perez, Kimberly; Quesenberry, Peter J.; Chatterjee, Devasis

    2015-01-01

    Extracellular vesicles (EVs) are secreted from many cells, carrying cargoes including proteins and nucleic acids. Research has shown that EVs play a role in a variety of biological processes including immunity, bone formation and recently they have been implicated in promotion of a metastatic phenotype. EVs were isolated from HCT116 colon cancer cells, 1459 non-malignant colon fibroblast cells, and tumor and normal colon tissue from a patient sample. Co-cultures were performed with 1459 cells and malignant vesicles, as well as HCT116 cells and non-malignant vesicles. Malignant phenotype was measured using soft agar colony formation assay. Co-cultures were also analyzed for protein levels using mass spectrometry. The importance of 14-3-3 zeta/delta in transfer of malignant phenotype was explored using siRNA. Additionally, luciferase reporter assay was used to measure the transcriptional activity of NF-κB. This study demonstrates the ability of EVs derived from malignant colon cancer cell line and malignant patient tissue to induce the malignant phenotype in non-malignant colon cells. Similarly, EVs derived from non-malignant colon cell lines and normal patient tissue reversed the malignant phenotype of HCT116 cells. Cells expressing an EV-induced malignant phenotype showed increased transcriptional activity of NF-κB which was inhibited by the NF--κB inhibitor, BAY117082. We also demonstrate that knock down of 14-3-3 zeta/delta reduced anchorage-independent growth of HCT116 cells and 1459 cells co-cultured with HCT derived EVs. Evidence of EV-mediated induction of malignant phenotype, and reversal of malignant phenotype, provides rational basis for further study of the role of EVs in tumorigenesis. Identification of 14-3-3 zeta/delta as up-regulated in malignancy suggests its potential as a putative drug target for the treatment of colorectal cancer

  4. [Nutritional epigenetics and epigenetic effects of human breast milk].

    Science.gov (United States)

    Lukoyanova, O L; Borovik, T E

    The article provides an overview of the current literature on nutritional epigenetics. There are currently actively studied hypothesis that nutrition especially in early life or in critical periods of the development, may have a role in modulating gene expression, and, therefore, have later effects on health in adults. Nutritional epigenetics concerns knowledge about the possible effects of nutrients on gene expression. Human breast milk is well-known for its ability in preventing necrotizing enterocolitis, infectious diseases, and also non-communicable diseases, such as obesity and related disorders. This paper discusses about presumed epigenetic effects of human breast milk and some its components. While evidence suggests that a direct relationship may exist of some components of human breast milk with epigenetic changes, the mechanisms involved are stillunclear.

  5. CHL1 is involved in human breast tumorigenesis and progression

    Energy Technology Data Exchange (ETDEWEB)

    He, Li-Hong [Medical Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Ma, Qin [Department of Oncology, The General Hospital of Tianjin Medical University, Tianjin (China); Shi, Ye-Hui [Medical Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Ge, Jie; Zhao, Hong-Meng [Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Li, Shu-Fen [Medical Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Tong, Zhong-Sheng, E-mail: 83352162@qq.com [Medical Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China)

    2013-08-23

    Highlights: •CHL1 is down-regulation in breast cancer tissues. •Down-regulation of CHL1 is related to high grade. •Overexpression of CHL1 inhibits breast cancer cell proliferation and invasion in vitro. •CHL1 deficiency induces breast cancer cell proliferation and invasion both in vitro and in vivo. -- Abstract: Neural cell adhesion molecules (CAM) play important roles in the development and regeneration of the nervous system. The L1 family of CAMs is comprised of L1, Close Homolog of L1 (CHL1, L1CAM2), NrCAM, and Neurofascin, which are structurally related trans-membrane proteins in vertebrates. Although the L1CAM has been demonstrated play important role in carcinogenesis and progression, the function of CHL1 in human breast cancer is limited. Here, we found that CHL1 is down-regulated in human breast cancer and related to lower grade. Furthermore, overexpression of CHL1 suppresses proliferation and invasion in MDA-MB-231 cells and knockdown of CHL1 expression results in increased proliferation and invasion in MCF7 cells in vitro. Finally, CHL1 deficiency promotes tumor formation in vivo. Our results may provide a strategy for blocking breast carcinogenesis and progression.

  6. CHL1 is involved in human breast tumorigenesis and progression

    International Nuclear Information System (INIS)

    He, Li-Hong; Ma, Qin; Shi, Ye-Hui; Ge, Jie; Zhao, Hong-Meng; Li, Shu-Fen; Tong, Zhong-Sheng

    2013-01-01

    Highlights: •CHL1 is down-regulation in breast cancer tissues. •Down-regulation of CHL1 is related to high grade. •Overexpression of CHL1 inhibits breast cancer cell proliferation and invasion in vitro. •CHL1 deficiency induces breast cancer cell proliferation and invasion both in vitro and in vivo. -- Abstract: Neural cell adhesion molecules (CAM) play important roles in the development and regeneration of the nervous system. The L1 family of CAMs is comprised of L1, Close Homolog of L1 (CHL1, L1CAM2), NrCAM, and Neurofascin, which are structurally related trans-membrane proteins in vertebrates. Although the L1CAM has been demonstrated play important role in carcinogenesis and progression, the function of CHL1 in human breast cancer is limited. Here, we found that CHL1 is down-regulated in human breast cancer and related to lower grade. Furthermore, overexpression of CHL1 suppresses proliferation and invasion in MDA-MB-231 cells and knockdown of CHL1 expression results in increased proliferation and invasion in MCF7 cells in vitro. Finally, CHL1 deficiency promotes tumor formation in vivo. Our results may provide a strategy for blocking breast carcinogenesis and progression

  7. Vitamin D content in human breast milk

    DEFF Research Database (Denmark)

    Við Streym, Susanna; Højskov, Carsten S; Møller, Ulla Kristine

    2016-01-01

    BACKGROUND: Parents are advised to avoid the direct sun exposure of their newborns. Therefore, the vitamin D status of exclusively breastfed newborns is entirely dependent on the supply of vitamin D from breast milk. OBJECTIVES: We explored concentrations of ergocalciferol (vitamin D2......) and cholecalciferol (vitamin D3) (vitamin D) and 25-hydroxivitamin D2 plus D3 (25-hydroxyvitamin D [25(OH)D]) in foremilk and hindmilk during the first 9 mo of lactation and identified indexes of importance to the concentrations. DESIGN: We collected blood and breast-milk samples from mothers at 2 wk (n = 107), 4 mo......, (n = 90), and 9 mo (n = 48) postpartum. Blood samples from infants were collected 4 and 9 mo after birth. We measured concentrations of vitamin D metabolites in blood and milk samples with the use of liquid chromatography-tandem mass spectrometry. RESULTS: Concentrations of vitamin D and 25(OH)D...

  8. Proteomics analysis of human breast milk to assess breast cancer risk.

    Science.gov (United States)

    Aslebagh, Roshanak; Channaveerappa, Devika; Arcaro, Kathleen F; Darie, Costel C

    2018-02-01

    Detection of breast cancer (BC) in young women is challenging because mammography, the most common tool for detecting BC, is not effective on the dense breast tissue characteristic of young women. In addition to the limited means for detecting their BC, young women face a transient increased risk of pregnancy-associated BC. As a consequence, reproductively active women could benefit significantly from a tool that provides them with accurate risk assessment and early detection of BC. One potential method for detection of BC is biochemical monitoring of proteins and other molecules in bodily fluids such as serum, nipple aspirate, ductal lavage, tear, urine, saliva and breast milk. Of all these fluids, only breast milk provides access to a large volume of breast tissue, in the form of exfoliated epithelial cells, and to the local breast environment, in the form of molecules in the milk. Thus, analysis of breast milk is a non-invasive method with significant potential for assessing BC risk. Here we analyzed human breast milk by mass spectrometry (MS)-based proteomics to build a biomarker signature for early detection of BC. Ten milk samples from eight women provided five paired-groups (cancer versus control) for analysis of dysregulatedproteins: two within woman comparisons (milk from a diseased breast versus a healthy breast of the same woman) and three across women comparisons (milk from a woman with cancer versus a woman without cancer). Despite a wide range in the time between milk donation and cancer diagnosis (cancer diagnosis occurred from 1 month before to 24 months after milk donation), the levels of some proteins differed significantly between cancer and control in several of the five comparison groups. These pilot data are supportive of the idea that molecular analysis of breast milk will identify proteins informative for early detection and accurate assessment of BC risk, and warrant further research. Data are available via ProteomeXchange with identifier

  9. [Soy isoflavones and human health: breast cancer and puberty timing].

    Science.gov (United States)

    Valladares, Luis; Garrido, Argelia; Sierralta, Walter

    2012-04-01

    Accumulated exposure to high levels of estrogen is associated with an increased incidence of breast cancer. Thus, factors such as early puberty, late menopause and hormone replacement therapy are considered to be risk factors, whereas early childbirth, breastfeeding and puberty at a later age are known to consistently decrease the lifetime breast cancer risk. Epidemiological studies suggest that consumption of isoflavones correlates with a lower incidence of breast cancer. Data from human intervention studies show that the effects of isoflavones on early breast cancer markers differ between pre- and post-menopausal women. The reports from experimental animals (rats and mice) on mammary tumors are variable. These results taken together with heterogeneous outcomes of human interventions, have led to a controversy surrounding the intake of isoflavones to reduce breast cancer risk. This review summarizes recent studies and analyzes factors that could explain the variability of results. In mammary tissue, from the cellular endocrine viewpoint, we analyze the effect of isoflavones on the estrogen receptor and their capacity to act as agonists or antagonists. On the issue of puberty timing, we analyze the mechanisms by which girls, but not boys, with higher prepuberal isoflavone intakes appear to enter puberty at a later age.

  10. Detection of Volatile Metabolites of Garlic in Human Breast Milk

    Science.gov (United States)

    Scheffler, Laura; Sauermann, Yvonne; Zeh, Gina; Hauf, Katharina; Heinlein, Anja; Sharapa, Constanze; Buettner, Andrea

    2016-01-01

    The odor of human breast milk after ingestion of raw garlic at food-relevant concentrations by breastfeeding mothers was investigated for the first time chemo-analytically using gas chromatography−mass spectrometry/olfactometry (GC-MS/O), as well as sensorially using a trained human sensory panel. Sensory evaluation revealed a clear garlic/cabbage-like odor that appeared in breast milk about 2.5 h after consumption of garlic. GC-MS/O analyses confirmed the occurrence of garlic-derived metabolites in breast milk, namely allyl methyl sulfide (AMS), allyl methyl sulfoxide (AMSO) and allyl methyl sulfone (AMSO2). Of these, only AMS had a garlic-like odor whereas the other two metabolites were odorless. This demonstrates that the odor change in human milk is not related to a direct transfer of garlic odorants, as is currently believed, but rather derives from a single metabolite. The formation of these metabolites is not fully understood, but AMSO and AMSO2 are most likely formed by the oxidation of AMS in the human body. The excretion rates of these metabolites into breast milk were strongly time-dependent with large inter-individual differences. PMID:27275838

  11. Organochlorine Pesticides And Pcbs In Human Breast Milk ...

    African Journals Online (AJOL)

    One hundred and Fifty (150) samples of human breast milk (colostrums) collected from donors patronizing a postnatal center in Nigeria were analyzed for the levels of lindane, total DDT and total PCBs residues. Donors were stratified with respect to factors that may affect accumulation of these compounds such as age, ...

  12. Human Papillomavirus (HPV) in breast tumors: prevalence in a group of Mexican patients

    International Nuclear Information System (INIS)

    León, David Cantu de; Montiel, Delia Pérez; Nemcova, Jana; Mykyskova, Iva; Turcios, Elmer; Villavicencio, Verónica; Cetina, Lucely; Coronel, Alberto; Hes, Ondraj

    2009-01-01

    Breast cancer is one of the main health problems in developed countries, occupying first place in mortality in women. It is well-known that there are risk factors associated with breast cancer development. Nonetheless, in 50–80% of cases known risk factors have not been identified, this has generated the attempt to identify new factors related with this neoplasia as viral infections. The aim of this work is investigate the prevalence of HPV DNA in patients with breast lesions at the Instituto Nacional de Cancerologia de Mexico. Fifty-one cases of breast cancer were selected from the files of the institute and compared by age and tumor size with 43 cases of non malignant breast lesions (fibroadenoma, fibrocystic disease and phyllodes tumor). Paraffin embedded specimens were selected, HPV DNA was analyzed by polymerase chain reaction (PCR) and sequenced for different types of HPV in case of positivity for HPV-DNA. Descriptive analysis of clinical and pathological variables was performed and comparisons between positive and negative cases was done. All patients were mexican, mean age was 53.3, median age of menarche was 13 and median tumor size 9 cms. Cervicovaginal cytology was performed to all patients, 1 patient (1.9%) of cancer group had HPV and none in the other group, no cases were diagnosed with cervical dysplasia. In the group of carcinomas 36 (70.5%) were negative and 15 (29.4%) were positive to HPV-DNA, 10(66.6%) were positive for HPV 16, 3(20%) for HPV 18, two cases (13.4%) were positive for both. In the group of benign conditions all were negative to HPV-DNA. Presence of HPV in breast cancer in our group of cases is high in comparison to other authors; larger numbers of cases need to be analyzed in order to establish the exact role of this virus in the pathogenesis of breast cancer

  13. Human Papillomavirus (HPV in breast tumors: prevalence in a group of Mexican patients

    Directory of Open Access Journals (Sweden)

    Cetina Lucely

    2009-01-01

    Full Text Available Abstract Background Breast cancer is one of the main health problems in developed countries, occupying first place in mortality in women. It is well-known that there are risk factors associated with breast cancer development. Nonetheless, in 50–80% of cases known risk factors have not been identified, this has generated the attempt to identify new factors related with this neoplasia as viral infections. The aim of this work is investigate the prevalence of HPV DNA in patients with breast lesions at the Instituto Nacional de Cancerologia de Mexico. Methods Fifty-one cases of breast cancer were selected from the files of the institute and compared by age and tumor size with 43 cases of non malignant breast lesions (fibroadenoma, fibrocystic disease and phyllodes tumor. Paraffin embedded specimens were selected, HPV DNA was analyzed by polymerase chain reaction (PCR and sequenced for different types of HPV in case of positivity for HPV-DNA. Descriptive analysis of clinical and pathological variables was performed and comparisons between positive and negative cases was done. Results All patients were mexican, mean age was 53.3, median age of menarche was 13 and median tumor size 9 cms. Cervicovaginal cytology was performed to all patients, 1 patient (1.9% of cancer group had HPV and none in the other group, no cases were diagnosed with cervical dysplasia. In the group of carcinomas 36 (70.5% were negative and 15 (29.4% were positive to HPV-DNA, 10(66.6% were positive for HPV 16, 3(20% for HPV 18, two cases (13.4% were positive for both. In the group of benign conditions all were negative to HPV-DNA. Conclusion Presence of HPV in breast cancer in our group of cases is high in comparison to other authors; larger numbers of cases need to be analyzed in order to establish the exact role of this virus in the pathogenesis of breast cancer.

  14. C-reactive protein and serum amyloid A levels in discriminating malignant from non-malignant pleural effusion

    Directory of Open Access Journals (Sweden)

    Hala Mohamed Shalaby Samaha

    2015-10-01

    Conclusion: Measurement of SAA and CRP levels in pleural fluid has good diagnostic utility in differentiation between malignant and non-malignant pleural effusion and pleural SAA has a better diagnostic performance than CRP.

  15. Enhancer of the rudimentary gene homologue (ERH expression pattern in sporadic human breast cancer and normal breast tissue

    Directory of Open Access Journals (Sweden)

    Knüchel Ruth

    2008-05-01

    Full Text Available Abstract Background The human gene ERH (Enhancer of the Rudimentary gene Homologue has previously been identified by in silico analysis of four million ESTs as a gene differentially expressed in breast cancer. The biological function of ERH protein has not been fully elucidated, however functions in cell cycle progression, pyrimidine metabolism a possible interaction with p21(Cip1/Waf1 via the Ciz1 zinc finger protein have been suggested. The aim of the present study was a systematic characterization of ERH expression in human breast cancer in order to evaluate possible clinical applications of this molecule. Methods The expression pattern of ERH was analyzed using multiple tissue northern blots (MTN on a panel of 16 normal human tissues and two sets of malignant/normal breast and ovarian tissue samples. ERH expression was further analyzed in breast cancer and normal breast tissues and in tumorigenic as well as non-tumorigenic breast cancer cell lines, using quantitative RT-PCR and non-radioisotopic in situ hybridization (ISH. Results Among normal human tissues, ERH expression was most abundant in testis, heart, ovary, prostate, and liver. In the two MTN sets of malignant/normal breast and ovarian tissue,ERH was clearly more abundantly expressed in all tumours than in normal tissue samples. Quantitative RT-PCR analyses showed that ERH expression was significantly more abundant in tumorigenic than in non-tumorigenic breast cancer cell lines (4.5-fold; p = 0.05, two-tailed Mann-Whitney U-test; the same trend was noted in a set of 25 primary invasive breast cancers and 16 normal breast tissue samples (2.5-fold; p = 0.1. These findings were further confirmed by non-radioisotopic ISH in human breast cancer and normal breast tissue. Conclusion ERH expression is clearly up-regulated in malignant as compared with benign breast cells both in primary human breast cancer and in cell models of breast cancer. Since similar results were obtained for ovarian

  16. [Breast is best--human milk for premature infants].

    Science.gov (United States)

    Riskin, Arieh; Bader, David

    2003-03-01

    Nutrition for preterm babies is aimed at achieving expected intrauterine growth and accretion of nutrients. Early trophic feedings should be started as soon as possible for gastrointestinal priming. Mother's (breast) milk is the best food for preterm babies. Its advantages are in host defence, nutritional components and suitability for gut absorption, as well as its psychological and developmental value. The limitations of human milk for preterm babies, mainly in protein and minerals, can be compensated for by using powdered human milk fortifier. Sucking skills usually mature around 34 weeks, corrected gestational age. Thus, small preemies are initially fed by orogastric tubes, meaning that expressed breast milk is used. Support of lactation in mothers of preemies mandates protection of the mother and child bonding process and early skin to skin contact ("kangeroo care"). Methods for storage of expressed breast milk and the recommended length of storage are discussed. Milk bank mandates pasteurization and freezing of the donors' milk. Most of the nutritional and immunological advantages of human milk are preserved after such treatments. Cytomegalovirus (CMV) infections in preterm infants, that were acquired from mother's expressed breast milk, are not uncommon, and require further attention.

  17. AFM indentation study of breast cancer cells

    International Nuclear Information System (INIS)

    Li, Q.S.; Lee, G.Y.H.; Ong, C.N.; Lim, C.T.

    2008-01-01

    Mechanical properties of individual living cells are known to be closely related to the health and function of the human body. Here, atomic force microscopy (AFM) indentation using a micro-sized spherical probe was carried out to characterize the elasticity of benign (MCF-10A) and cancerous (MCF-7) human breast epithelial cells. AFM imaging and confocal fluorescence imaging were also used to investigate their corresponding sub-membrane cytoskeletal structures. Malignant (MCF-7) breast cells were found to have an apparent Young's modulus significantly lower (1.4-1.8 times) than that of their non-malignant (MCF-10A) counterparts at physiological temperature (37 deg. C), and their apparent Young's modulus increase with loading rate. Both confocal and AFM images showed a significant difference in the organization of their sub-membrane actin structures which directly contribute to their difference in cell elasticity. This change may have facilitated easy migration and invasion of malignant cells during metastasis

  18. An early history of human breast cancer: West meets East.

    Science.gov (United States)

    Yan, Shou-He

    2013-09-01

    Cancer has been increasingly recognized as a global issue. This is especially true in countries like China, where cancer incidence has increased likely because of changes in environment and lifestyle. However, cancer is not a modern disease; early cases have been recorded in ancient medical books in the West and in China. Here, we provide a brief history of cancer, focusing on cancer of the breast, and review the etymology of ai, the Chinese character for cancer. Notable findings from both Western and Chinese traditional medicine are presented to give an overview of the most important, early contributors to our evolving understanding of human breast cancer. We also discuss the earliest historical documents to record patients with breast cancer.

  19. Dissection of a stem cell hierarchy in the human breast

    DEFF Research Database (Denmark)

    Rubner Fridriksdottir, Agla Jael

    and apoptosis during each menstrual cycle. These changes are most prominent during pregnancy, lactation and involution after breast feeding. These highly dynamic changes are thought to rely on the presence of a breast epithelial stem cell population (reviewed in (Fridriksdottir et al. 2005)). Nevertheless......, cellular pathways that contribute to adult human breast gland architecture and cell lineages have not been described. Here, I identify a candidate stem cell niche in ducts, and zones containing progenitor cells in lobules (Villadsen and Fridriksdottir et al. 2007). Putative stem cells residing in ducts......-rich extracellular matrix gel. Staining for the epithelial lineage markers, cytokeratins K14 and K19, further reveals multipotent cells in the stem cell zone and three lineage- restricted cell types outside this zone. Multiparameter cell sorting and functional characterization with reference to anatomical sites...

  20. Breast Cancer Mortality In Brazil: Correlation With Human Development Index

    Directory of Open Access Journals (Sweden)

    Mara Rejane Barroso Barcelos

    2017-01-01

    Full Text Available Background: Mortality from breast cancer decreased in high-income countries, while countries with middle and low incomes as Brazil still has upward trend. However, large geographical variations among the federal units are observed in the country. The aim of the study was to evaluate the trend of specific mortality from breast cancer in women over 20 years old years among different states of Brazil from 1996 to 2012.  Methods and Findings: Ecological study, using linear regression model for temporal analysis of specific mortality coefficient from malignant neoplasm of breast. We also checked the degree of its correlation with the HDI for the states of Brazil during the stated period. There was an increase in the specific mortality rate for malignant neoplasm of the breast in order of 33%, with range from 23.2 to 30.8 / 100,000 inhabitants. The states with the highest human development HDI in 2010, showed the largest specific mortality rates of breast cancer. Conclusion: Taking the trends of mortality from cancer an important role, this study confirms the need for improvements in mammography coverage, following radiological lesions suspected and access to appropriate therapy.

  1. 99MTC Alpha-Fetoprotein: A Novel, Specific Agent for the Detection of Human Breast Cancer

    National Research Council Canada - National Science Library

    Line, Bruce

    1998-01-01

    .... We have demonstrated that technetium-99m radiolabeled human alpha-fetoprotein (99mTc AFP) localizes in human breast cancer cells in-vivo, most likely concentrating in breast cancer cells due to a specific receptor not found in normal adult breast tissue...

  2. 99MTC Alpha-Fetoprotein: A Novel, Specific Agent for the Detection of Human Breast Cancer

    National Research Council Canada - National Science Library

    Line, Bruce

    1999-01-01

    .... We have demonstrated that technetium-99m radiolabeled human alpha-fetoprotein (99mTc AFP) localizes in human breast cancer cells in-vivo, most likely concentrating in breast cancer cells due to a specific receptor not found in normal adult breast tissue...

  3. Characterization of human breast cancer by scanning acoustic microscopy

    Science.gov (United States)

    Chen, Di; Malyarenko, Eugene; Seviaryn, Fedar; Yuan, Ye; Sherman, Mark; Bandyopadhyay, Sudeshna; Gierach, Gretchen; Greenway, Christopher W.; Maeva, Elena; Strumban, Emil; Duric, Neb; Maev, Roman

    2013-03-01

    Objectives: The purpose of this study was to characterize human breast cancer tissues by the measurement of microacoustic properties. Methods: We investigated eight breast cancer patients using acoustic microscopy. For each patient, seven blocks of tumor tissue were collected from seven different positions around a tumor mass. Frozen sections (10 micrometer, μm) of human breast cancer tissues without staining and fixation were examined in a scanning acoustic microscope with focused transducers at 80 and 200 MHz. Hematoxylin and Eosin (H and E) stained sections from the same frozen breast cancer tissues were imaged by optical microscopy for comparison. Results: The results of acoustic imaging showed that acoustic attenuation and sound speed in cancer cell-rich tissue regions were significantly decreased compared with the surrounding tissue regions, where most components are normal cells/tissues, such as fibroblasts, connective tissue and lymphocytes. Our observation also showed that the ultrasonic properties were influenced by arrangements of cells and tissue patterns. Conclusions: Our data demonstrate that attenuation and sound speed imaging can provide biomechanical information of the tumor and normal tissues. The results also demonstrate the potential of acoustic microscopy as an auxiliary method for operative detection and localization of cancer affected regions.

  4. Resources for Precision Analysis of Human Breast Cancer

    Science.gov (United States)

    2000-08-01

    correlation chemistry are necessary to confirm this observation, the, is different between the in vitro and in vivo situations, pattern of expression is...Feunteun 44. Mandinova A, Atar D, Schafer BW, Spiess M, Aebi U, Heizmann C1 J, Schnitt S, Livingston DM: Location of BRCA1 in human breast and Distinct...with progression-free survival, in prostate cancer [20]. expression but strong staining by immunohisto-S • chemistry were positive by western blot

  5. Induction of apoptosis by eugenol in human breast cancer cells

    International Nuclear Information System (INIS)

    Vidhya, N.; Niranjali Devaraj, S.

    2011-01-01

    In the present study, potential anticancer effect of eugenol on inhibition of cell proliferation and induction of apoptosis in human MCF-7 breast cancer cells was investigated. Induction of cell death by eugenol was evaluated following MTT assay and monitoring lactate dehydrogenase released into the culture medium for cell viability and cytotoxicity, giemsa staining for morphological alterations, fluorescence microscopy analysis of cells using ethidium bromide and acridine orange and quantitation of DNA fragments for induction of apoptosis. Effect of eugenol on intracellular redox status of the human breast cancer cells was assessed by determining the level of glutathione and lipid peroxidation products (TBARS). Eugenol treatment inhibited the growth and proliferation of human MCF-7 breast cancer cells through induction of cell death, which was dose and time dependent. Microscopic examination of eugenol treated cells showed cell shrinkage, membrane blebbing and apoptotic body formation. Further, eugenol treatment also depleted the level of intracellular glutathione and increased the level of lipid peroxidation. The dose dependent increase in the percentage of apoptotic cells and DNA fragments suggested that apoptosis was involved in eugenol induced cell death and apoptosis might have played a role in the chemopreventive action of eugenol. (author)

  6. Imaging Proteolysis by Living Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Mansoureh Sameni

    2000-01-01

    Full Text Available Malignant progression is accompanied by degradation of extracellular matrix proteins. Here we describe a novel confocal assay in which we can observe proteolysis by living human breast cancer cells (BT20 and BT549 through the use of quenchedfluorescent protein substrates. Degradation thus was imaged, by confocal optical sectioning, as an accumulation of fluorescent products. With the BT20 cells, fluorescence was localized to pericellular focal areas that coincide with pits in the underlying matrix. In contrast, fluorescence was localized to intracellular vesicles in the BT549 cells, vesicles that also label for lysosomal markers. Neither intracellular nor pericellular fluorescence was observed in the BT549 cells in the presence of cytochalasin B, suggesting that degradation occurred intracellularly and was dependent on endocytic uptake of substrate. In the presence of a cathepsin 13-selective cysteine protease inhibitor, intracellular fluorescence was decreased ~90% and pericellular fluorescence decreased 67% to 96%, depending on the protein substrate. Matrix metallo protease inhibitors reduced pericellular fluorescence ~50%, i.e., comparably to a serine and a broad spectrum cysteine protease inhibitor. Our results suggest that: 1 a proteolytic cascade participates in pericellular digestion of matrix proteins by living human breast cancer cells, and 2 the cysteine protease cathepsin B participates in both pericellular and intracellular digestion of matrix proteins by living human breast cancer cells.

  7. Altered serotonin physiology in human breast cancers favors paradoxical growth and cell survival.

    Science.gov (United States)

    Pai, Vaibhav P; Marshall, Aaron M; Hernandez, Laura L; Buckley, Arthur R; Horseman, Nelson D

    2009-01-01

    The breast microenvironment can either retard or accelerate the events associated with progression of latent cancers. However, the actions of local physiological mediators in the context of breast cancers are poorly understood. Serotonin (5-HT) is a critical local regulator of epithelial homeostasis in the breast and other organs. Herein, we report complex alterations in the intrinsic mammary gland serotonin system of human breast cancers. Serotonin biosynthetic capacity was analyzed in human breast tumor tissue microarrays using immunohistochemistry for tryptophan hydroxylase 1 (TPH1). Serotonin receptors (5-HT1-7) were analyzed in human breast tumors using the Oncomine database. Serotonin receptor expression, signal transduction, and 5-HT effects on breast cancer cell phenotype were compared in non-transformed and transformed human breast cells. In the context of the normal mammary gland, 5-HT acts as a physiological regulator of lactation and involution, in part by favoring growth arrest and cell death. This tightly regulated 5-HT system is subverted in multiple ways in human breast cancers. Specifically, TPH1 expression undergoes a non-linear change during progression, with increased expression during malignant progression. Correspondingly, the tightly regulated pattern of 5-HT receptors becomes dysregulated in human breast cancer cells, resulting in both ectopic expression of some isoforms and suppression of others. The receptor expression change is accompanied by altered downstream signaling of 5-HT receptors in human breast cancer cells, resulting in resistance to 5-HT-induced apoptosis, and stimulated proliferation. Our data constitutes the first report of direct involvement of 5-HT in human breast cancer. Increased 5-HT biosynthetic capacity accompanied by multiple changes in 5-HT receptor expression and signaling favor malignant progression of human breast cancer cells (for example, stimulated proliferation, inappropriate cell survival). This occurs

  8. Colorectal cancer and non-malignant respiratory disease in asbestos cement and cement workers

    International Nuclear Information System (INIS)

    Jacobsson, K.

    1993-09-01

    Radiologically visible parenchymal changes (small opacities >= 1/0;ILO 1980 classification) were present in 20% of a sample of workers (N=174), employed for 20 years (median) in an asbestos cement plant. Exposure-response relationships were found, after controlling for age and smoking habits. In a sample of asbestos cement workers with symptoms and signs suggestive of pulmonary disease (N=33), increased lung density measured by x-ray computed tomography, and reduced static lung volumes and lung compliance was found. In a cohort of asbestos cement workers (N=1.929) with an estimated median exposure of 1.2 fibres/ml, the mortality from non-malignant respiratory disease was increased in comparison to a regional reference cohort (N=1.233). A two-to three-fold increase of non-malignant respiratory mortality was noted among workers employed for more than a decade in the asbestos cement plant, compared to cement workers (N=1.526), who in their turn did not experience and increased risk compared to the general population. In the cohorts of asbestos cement and cement workers, there was a tow-to three-fold increased incidence of cancer in the right part of the colon, compared to the general population as well as to external reference cohorts of other industrial workers (N=3.965) and fishermen (N=8.092). A causal relation with the exposure to mineral dust and fibres was supported by the findings of higher risk estimated in subgroups with high cumulated asbestos doses or longer duration of cement work. The incidence of cancer in the left part of the colon was not increased. Morbidity data, but not mortality data, disclosed the subsite-specific risk pattern. Both asbestos cement workers and cement workers has an increased incidence of rectal cancer, compared with the general population, and with the fishermen. The risk was, however, of the same magnitude among the other industrial workers. 181 refs

  9. Non-malignant consequences of decreasing asbestos exposure in the Brazil chrysotile mines and mills.

    Science.gov (United States)

    Bagatin, E; Neder, J A; Nery, L E; Terra-Filho, M; Kavakama, J; Castelo, A; Capelozzi, V; Sette, A; Kitamura, S; Favero, M; Moreira-Filho, D C; Tavares, R; Peres, C; Becklake, M R

    2005-06-01

    To investigate the consequences of improvement in the workplace environment over six decades (1940-96) in asbestos miners and millers from a developing country (Brazil). A total of 3634 Brazilian workers with at least one year of exposure completed a respiratory symptoms questionnaire, chest radiography, and a spirometric evaluation. The study population was separated into three groups whose working conditions improved over time: group I (1940-66, n = 180), group II (1967-76, n = 1317), and group III (1977-96, n = 2137). Respiratory symptoms were significantly related to spirometric abnormalities, smoking, and latency time. Breathlessness, in particular, was also associated with age, pleural abnormality and increased cumulative exposure to asbestos fibres. The odds ratios (OR) for parenchymal and/or non-malignant pleural disease were significantly lower in groups II and III compared to group I subjects (0.29 (0.12-0.69) and 0.19 (0.08-0.45), respectively), independent of age and smoking status. Similar results were found when groups were compared at equivalent latency times (groups I v II: 30-45 years; groups II v III: 20-25 years). Ageing, dyspnoea, past and current smoking, and radiographic abnormalities were associated with ventilatory impairment. Lower spirometric values were found in groups I and II compared to group III: lung function values were also lower in higher quartiles of latency and of cumulative exposure in these subjects. Progressive improvement in occupational hygiene in a developing country is likely to reduce the risk of non-malignant consequences of dust inhalation in asbestos miners and millers.

  10. Persistent organic pollutants in human breast milk from Asian countries

    International Nuclear Information System (INIS)

    Tanabe, Shinsuke; Kunisue, Tatsuya

    2007-01-01

    In this paper, we concisely reviewed the contamination of persistent organic pollutants (POPs) such as polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), biphenyls (PCBs), dichlorodiphenyltrichloroethane and its metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), chlordane compounds (CHLs), hexachlorobenzene (HCB) in human breast milk collected from Asian countries such as Japan, China, Philippines, Vietnam, Cambodia, India, Malaysia, and Indonesia during 1999-2003. Dioxins, PCBs, CHLs in Japanese, and DDTs in Vietnamese, Chinese, Cambodian, Malaysian, and HCHs in Chinese, Indian, and HCB in Chinese breast milk were predominant. In India, levels of dioxins and related compounds (DRCs) in the mothers living around the open dumping site were notably higher than those from the reference site and other Asian developing countries, indicating that significant pollution sources of DRCs are present in the dumping site of India and the residents there have been exposed to relatively higher levels of these contaminants possibly via bovine milk. - Contamination aspects of POPs in human breast milk from Asian countries were characterized

  11. Characterization of Candidate probionts isolated from human breast milk.

    Science.gov (United States)

    Khalkhali, S; Mojgani, N

    2017-05-20

    This study was designed to isolate and identify the potential probionts present in 32 healthy mothers' breast milk. Microbial culture media and 16SrRNA sequencing were used to isolate and identify the bacteria and all isolates were analyzed for their antagonistic potential, resistance to acidic pH, bile salts and survival under simulated gastric and intestinal conditions. The colonization potential was further assessed based on adherence to human enterocyte-like Caco-2 cell lines. The breast milk samples harbored significant numbers of Gram positive and catalase negative (85%) bacteria. Based on 16SrRNA sequencing, these isolates were identified as Lactobacillus casei, L.gasseri, L.fermentum, L.plantarum, Pediococcus acidilactici, and Enterococcus facieum. Among the isolates, P. acidilactici was the most frequent species (71%) present in these samples. Few Gram and catalase positive isolates, Staphylococcus aureus and S.hominiis were also observed. The isolates were viable and unviable in pH 3 and 1.5, respectively, while all isolates survived in 1.0% bile salt. As putative probionts, P.acidilactici 1C showed a significantly higher percentage of adhesion to Caco-2 cells (p< 0.05)than the other two isolates L.plantarum 7A and E.facieum 2C. Bacterial strains isolated from human breast milk were shown to have probiotic properties including anti-infective protection and may be considered as future therapeutics for infants.

  12. Persistent organic pollutants in human breast milk from Asian countries

    Energy Technology Data Exchange (ETDEWEB)

    Tanabe, Shinsuke [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790 8577, Ehime Prefecture (Japan)]. E-mail: shinsuke@agr.ehime-u.ac.jp; Kunisue, Tatsuya [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790 8577, Ehime Prefecture (Japan)

    2007-03-15

    In this paper, we concisely reviewed the contamination of persistent organic pollutants (POPs) such as polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), biphenyls (PCBs), dichlorodiphenyltrichloroethane and its metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), chlordane compounds (CHLs), hexachlorobenzene (HCB) in human breast milk collected from Asian countries such as Japan, China, Philippines, Vietnam, Cambodia, India, Malaysia, and Indonesia during 1999-2003. Dioxins, PCBs, CHLs in Japanese, and DDTs in Vietnamese, Chinese, Cambodian, Malaysian, and HCHs in Chinese, Indian, and HCB in Chinese breast milk were predominant. In India, levels of dioxins and related compounds (DRCs) in the mothers living around the open dumping site were notably higher than those from the reference site and other Asian developing countries, indicating that significant pollution sources of DRCs are present in the dumping site of India and the residents there have been exposed to relatively higher levels of these contaminants possibly via bovine milk. - Contamination aspects of POPs in human breast milk from Asian countries were characterized.

  13. Bone marrow-derived CD13+ cells sustain tumor progression: A potential non-malignant target for anticancer therapy.

    Science.gov (United States)

    Dondossola, Eleonora; Corti, Angelo; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

    2014-01-01

    Non-malignant cells found within neoplastic lesions express alanyl (membrane) aminopeptidase (ANPEP, best known as CD13), and CD13-null mice exhibit limited tumor growth and angiogenesis. We have recently demonstrated that a subset of bone marrow-derived CD11b + CD13 + myeloid cells accumulate within neoplastic lesions in several murine models of transplantable cancer to promote angiogenesis. If these findings were confirmed in clinical settings, CD11b + CD13 + myeloid cells could become a non-malignant target for the development of novel anticancer regimens.

  14. Rap1 integrates tissue polarity, lumen formation, and tumorigenicpotential in human breast epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, Masahiko; Nelson, Celeste M.; Myers, Connie A.; Bissell,Mina J.

    2006-09-29

    Maintenance of apico-basal polarity in normal breast epithelial acini requires a balance between cell proliferation, cell death, and proper cell-cell and cell-extracellular matrix signaling. Aberrations in any of these processes can disrupt tissue architecture and initiate tumor formation. Here we show that the small GTPase Rap1 is a crucial element in organizing acinar structure and inducing lumen formation. Rap1 activity in malignant HMT-3522 T4-2 cells is appreciably higher than in S1 cells, their non-malignant counterparts. Expression of dominant-negative Rap1 resulted in phenotypic reversion of T4-2 cells, led to formation of acinar structures with correct apico-basal polarity, and dramatically reduced tumor incidence despite the persistence of genomic abnormalities. The resulting acini contained prominent central lumina not observed when other reverting agents were used. Conversely, expression of dominant-active Rap1 in T4-2 cells inhibited phenotypic reversion and led to increased invasiveness and tumorigenicity. Thus, Rap1 acts as a central regulator of breast architecture, with normal levels of activation instructing apical polarity during acinar morphogenesis, and increased activation inducing tumor formation and progression to malignancy.

  15. INHIBITION OF SPONTANEOUS APOPTOSIS IN HUMAN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    邵志敏; 江明; 吴炅; 余黎民; 韩企夏; 张延璆; 沈镇宙

    1996-01-01

    Breast tumorigenesis proceeds through an accumulation of specific genetic alteration. Breast malignant transformation is dependent on not only the rate of cell production but also on apoptcsis,a genetically prograined process of autonomous ceil death. We investigated whether breast tumorigenesis involved an altered susceptibility to apoptosis and proliferation by examining normal breast epithelium and breast cancer sampies. We found there is a great inhibition of spontaneous apoptosis in breast cancer ceils compared with normal breast epithelium. The inhibition of apoptosis in breast cancer may contribute to neoplastic transformation.

  16. Molecular biology of breast cancer metastasis: Genetic regulation of human breast carcinoma metastasis

    International Nuclear Information System (INIS)

    Welch, Danny R; Steeg, Patricia S; Rinker-Schaeffer, Carrie W

    2000-01-01

    The present is an overview of recent data that describes the genetic underpinnings of the suppression of cancer metastasis. Despite the explosion of new information about the genetics of cancer, only six human genes have thus far been shown to suppress metastasis functionally. Not all have been shown to be functional in breast carcinoma. Several additional genes inhibit various steps of the metastatic cascade, but do not necessarily block metastasis when tested using in vivo assays. The implications of this are discussed. Two recently discovered metastasis suppressor genes block proliferation of tumor cells at a secondary site, offering a new target for therapeutic intervention

  17. Non-malignant causes of hypercalcemia in cancer patients: a frequent and neglected occurrence.

    Science.gov (United States)

    Soyfoo, M S; Brenner, K; Paesmans, M; Body, J J

    2013-05-01

    Hypercalcemia is a frequent finding in cancer patients and can be observed in any type of cancer. The physician in charge of cancer patients often ignores non-malignant causes of hypercalcemia. Our objective was to review the causes of hypercalcemia in a large series of cancer patients. We have retrospectively studied in a Cancer Centre all consecutive hypercalcemic (Ca> 10.5 mg/dl) patients over an 8-year period. Of 699 evaluated patients, 642 were analyzed after exclusion of patients whose hypercalcemia resolved after rehydration or who had a normal Ca level after correction for protein concentrations. Clinical information was gathered on the type of cancer, its histology, whether the disease was active or in complete remission, and on the presence of bone metastases. Biochemical data included serum Ca, P(i), proteins in all patients, PTH in most patients, and PTHrP, 25OH-Vitamin D, 1,25(OH)(2)-Vitamin D, TSH, and T4 in selected cases. By order of decreasing frequency, the main causes of hypercalcemia were cancer (69.0 %), primary hyperparathyroidism (24.6 %), hyperthyroidism (2.2 %), milk alkali syndrome (0.9 %), and sarcoidosis (0.45 %). In cancer-related causes, bone metastases accounted for 53.0 % of the cases, humoral hypercalcemia of malignancy (HHM) for 35.3 % while there were 11.7 % of cases apparently due to both HHM and bone metastases. Hypercalcemia was not due to cancer in 97 % (84/87) of the patients who were in complete remission. Even in patients with active neoplastic disease, the number of patients whose hypercalcemia was not due to cancer remained clinically relevant (115/555 = 20.5 %). In the 158 patients with primary hyperparathyroidism, 92 patients were in complete remission and 66 patients had active neoplastic disease. In this large series of hypercalcemia in cancer patients, the cause was not due to cancer in almost one third of the cases. Most patients considered to be in complete remission had hypercalcemia due to a benign

  18. Therapeutic effects of diaphragmatic plication for acquired unilateral non-malignant diaphragm paralysis in twenty patients

    Directory of Open Access Journals (Sweden)

    Reza Bagheri

    2013-12-01

    Full Text Available Background: Acquired paralysis of the diaphragm is a condition caused by trauma, surgical injuries, (lung cancer surgery, esophageal surgery, cardiac surgery, thoracic surgery, and is sometimes of an unknown etiology. It can lead to dyspnea and can affect ventilatory function and patients activity. Diaphragmatic plication is a treatment method which decreases inconsistent function of diaphragm. The aim of this study is to evaluate the outcome of diaphragmatic plication in patients with acquired unilateral non-malignant diaphragmatic paralysis. Methods: From 1991 to 2011, 20 patients with acquired unilateral diaphragmatic paralysis who underwent surgery enrolled in our study in Ghaem Hospital Mashhad University of Medical Science. Patients were evaluated in terms of age, sex, BMI, clinical symptoms, dyspnea score (DS, etiology of paralysis, diagnostic methods, respiratory function tests and complication of surgery. Some tests including dyspnea score were carried out again six months after surgery. We evaluated patients with SPSS version 11.5 and Paired t-test or nonparametric equivalent. Results: Twenty patients enrolled in our study. 14 were male and 6 were female. The mean age was 58 years and the average time interval between diagnosis to surgical treatment was 38.3 months. Acquired diaphragmatic paralysis was mostly caused by trauma (in 11 patients and almost occurred on the left side (in 15 patients. Diagnostic methods included chest x-ray, CT scan, ultrasonography and sniff. Test prior to surgery the average FVC was 41.4±7 percent and the average FEV1 was 52.4±6 percent and after surgery they were 80.1±8.6 percent and 74.4±1 percent respectively. The average increase in FEV1 and FVC 63.4±4, 61.1±7.8. Performing surgery also leads to a noticeable improvement in dyspnea score in our study. Conclusion: In patients with acquired unilateral non-malignant diaphragm paralysis diaphragmatic plication is highly recommended due to the

  19. Prevotella timonensis sp. nov., isolated from a human breast abscess.

    Science.gov (United States)

    Glazunova, Olga O; Launay, Thierry; Raoult, Didier; Roux, Véronique

    2007-04-01

    Gram-negative anaerobic rods were isolated from a human breast abscess. Based on genotypic and phenotypic characteristics, the novel strain belonged to the genus Prevotella. Phylogenetic analysis based on 16S rRNA gene sequence comparisons showed that it was closely related to Prevotella buccalis (94 % 16S rRNA gene sequence similarity), Prevotella salivae (90 %) and Prevotella oris (89.1 %). The major cellular fatty acid was C(14 : 0) (19.5 %). The new isolate represents a novel species in the genus Prevotella, for which the name Prevotella timonensis sp. nov. is proposed. The type strain is strain 4401737(T) (=CIP 108522(T)=CCUG 50105(T)).

  20. Molecular Mechanisms of Metastasis Suppression in Human Breast Cancer

    Science.gov (United States)

    1997-07-01

    immune system? Ann N Y Acad Sci, JR, 1986, The role of NK cells in tumour growth and 741, 212-15. metastasis in beige mice. Nature, 284, 622-4. 89. Stone ...77. Simmons ML and Brick JO, 1969, The Laboratory 96. Senger DR, Brown LF, Claffey KP and Dvorak HF, Mouse. Hollaender A, ed. Englewood Cliffs, NJ...ranfe of huan tumo sme I I su ding the human chromosome 11 into the highly metastatic MDA-MB-435 breast tumorigenic phenotype of several tumor lines

  1. Radiotherapy for non-malignant disorders: state of the art and update of the evidence-based practice guidelines

    Science.gov (United States)

    Micke, O; Muecke, R

    2015-01-01

    Every year in Germany about 50,000 patients are referred and treated by radiotherapy (RT) for “non-malignant disorders”. This highly successful treatment is applied only for specific indications such as preservation or recovery of the quality of life by means of pain reduction or resolution and/or an improvement of formerly impaired physical body function owing to specific disease-related symptoms. Since 1995, German radiation oncologists have treated non-malignant disorders according to national consensus guidelines; these guidelines were updated and further developed over 3 years by implementation of a systematic consensus process to achieve national upgraded and accepted S2e clinical practice guidelines. Throughout this process, international standards of evaluation were implemented. This review summarizes most of the generally accepted indications for the application of RT for non-malignant diseases and presents the special treatment concepts. The following disease groups are addressed: painful degenerative skeletal disorders, hyperproliferative disorders and symptomatic functional disorders. These state of the art guidelines may serve as a platform for daily clinical work; they provide a new starting point for quality assessment, future clinical research, including the design of prospective clinical trials, and outcome research in the underrepresented and less appreciated field of RT for non-malignant disorders. PMID:25955230

  2. 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

  3. Faculty Communication Knowledge, Attitudes, and Skills Around Chronic Non-Malignant Pain Improve with Online Training.

    Science.gov (United States)

    Donovan, Anna K; Wood, Gordon J; Rubio, Doris M; Day, Hollis D; Spagnoletti, Carla L

    2016-11-01

    Many physicians struggle to communicate with patients with chronic, non-malignant pain (CNMP). Through the use of a Web module, the authors aimed to improve faculty participants' communication skills knowledge and confidence, use of skills in clinical practice, and actual communication skills. The module was implemented for faculty development among clinician-educators with university faculty appointments, outpatient clinical practices, and teaching roles. Participants completed the Collaborative Opioid Prescribing Education Risk Evaluation and Mitigation Strategy (COPE-REMS®) module, a free Web module designed to improve provider communication around opioid prescribing. Main study outcomes were improvements in CNMP communication knowledge, attitudes, and skills. Skills were assessed by comparing a subset of participants' Observed Structured Clinical Exam (OSCE) performance before and after the curriculum. Sixty-two percent of eligible participants completed the curriculum in 2013. Knowledge-based test scores improved with curriculum completion (75% vs. 90%; P communication skills on the OSCE improved after the curriculum (mean 67% vs. 79%, P = 0.03). Experienced clinician-educators improved their communication knowledge, attitudes, and skills in managing patients with CNMP after implementation of this curriculum. The improvements in attitudes were sustained at six months. A Web-based curriculum such as COPE-REMS® may be useful for other programs seeking improvement in faculty communication with patients who have CNMP. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. CD47 limits antibody dependent phagocytosis against non-malignant B cells.

    Science.gov (United States)

    Gallagher, Sandra; Turman, Sean; Lekstrom, Kristen; Wilson, Susan; Herbst, Ronald; Wang, Yue

    2017-05-01

    Recent studies have demonstrated the importance of CD47 in protecting malignant B cells from antibody dependent cellular phagocytosis (ADCP). Combined treatment of anti-CD47 and -CD20 antibodies synergistically augment elimination of tumor B cells in xenograft mouse models. This has led to the development of novel reagents that can potentially enhance killing of malignant B cells in patients. B cell depleting therapy is also a promising treatment for autoimmune patients. In the current study, we aimed to investigate whether or not CD47 protects non-malignant B cells from ADCP. We show that CD47 is expressed on all B cells in mice, with the highest level on plasma cells in bone marrow and spleen. Although its expression is dispensable for B cell development in mice, CD47 on B cells limits antibody mediated phagocytosis. B cell depletion following in vivo anti-CD19 treatment is more efficient in CD47-/- mice than in wild type mice. In vitro, both naïve and activated B cells from CD47-/- mice are more sensitive to ADCP than wild type B cells. Lastly, we show in an ADCP assay that blocking CD47 can enhance anti-CD19 antibody mediated phagocytosis of wild type B cells. These results suggest that in addition to its already demonstrated benefit in cancer, targeting CD47 may be used as an adjunct in combination with B cell depletion antibodies for treatment of autoimmune diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. The plasticity of human breast carcinoma cells is more than epithelial to mesenchymal conversion

    DEFF Research Database (Denmark)

    Petersen, Ole William; Nielsen, Helga Lind; Gudjonsson, Thorarinn

    2001-01-01

    The human breast comprises three lineages: the luminal epithelial lineage, the myoepithelial lineage, and the mesenchymal lineage. It has been widely accepted that human breast neoplasia pertains only to the luminal epithelial lineage. In recent years, however, evidence has accumulated that neopl...

  6. Glyphosate induces human breast cancer cells growth via estrogen receptors.

    Science.gov (United States)

    Thongprakaisang, Siriporn; Thiantanawat, Apinya; Rangkadilok, Nuchanart; Suriyo, Tawit; Satayavivad, Jutamaad

    2013-09-01

    Glyphosate is an active ingredient of the most widely used herbicide and it is believed to be less toxic than other pesticides. However, several recent studies showed its potential adverse health effects to humans as it may be an endocrine disruptor. This study focuses on the effects of pure glyphosate on estrogen receptors (ERs) mediated transcriptional activity and their expressions. Glyphosate exerted proliferative effects only in human hormone-dependent breast cancer, T47D cells, but not in hormone-independent breast cancer, MDA-MB231 cells, at 10⁻¹² to 10⁻⁶M in estrogen withdrawal condition. The proliferative concentrations of glyphosate that induced the activation of estrogen response element (ERE) transcription activity were 5-13 fold of control in T47D-KBluc cells and this activation was inhibited by an estrogen antagonist, ICI 182780, indicating that the estrogenic activity of glyphosate was mediated via ERs. Furthermore, glyphosate also altered both ERα and β expression. These results indicated that low and environmentally relevant concentrations of glyphosate possessed estrogenic activity. Glyphosate-based herbicides are widely used for soybean cultivation, and our results also found that there was an additive estrogenic effect between glyphosate and genistein, a phytoestrogen in soybeans. However, these additive effects of glyphosate contamination in soybeans need further animal study. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Prolactin-inducible proteins in human breast cancer cells

    International Nuclear Information System (INIS)

    Shiu, R.P.; Iwasiow, B.M.

    1985-01-01

    The mechanism of action of prolactin in target cells and the role of prolactin in human breast cancer are poorly understood phenomena. The present study examines the effect of human prolactin (hPRL) on the synthesis of unique proteins by a human breast cancer cell line, T-47D, in serum-free medium containing bovine serum albumin. [ 35 S]Methionine-labeled proteins were analysed by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis and fluorography. Treatment of cells with hPRL (1-1000 ng/ml) and hydrocortisone (1 microgram/ml) for 36 h or longer resulted in the synthesis and secretion of three proteins having molecular weights of 11,000, 14,000, and 16,000. Neither hPRL nor hydrocortisone alone induced these proteins. Of several other peptide hormones tested, only human growth hormone, a hormone structurally and functionally similar to hPRL, could replace hPRL in causing protein induction. These three proteins were, therefore, referred to as prolactin-inducible proteins (PIP). Each of the three PIPs was purified to homogeneity by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and specific antibodies were generated to them in rabbits. By immunoprecipitation and immunoblotting (Western blot) of proteins secreted by T-47D cells, it was demonstrated that the three PIPs were immunologically identical to one another. In addition, the 16-kDa and 14-kDa proteins (PIP-16 and PIP-14), and not the 11-kDa protein (PIP-11), incorporated [ 3 H]glycosamine. Furthermore, 2-deoxyglucose (2 mM) and tunicamycin (0.5 micrograms/ml), two compounds known to inhibit glycosylation, blocked the production of PIP-16 and PIP-14, with a concomitant increase in the accumulation of PIP-11

  8. Modulation of TIP60 by Human Papilloma Virus in Breast Cancer

    Science.gov (United States)

    2013-04-01

    1 AG________ Award Number: W81XWH-11-1-0687 Title Modulation of TIP60 by Human Papilloma Virus in Breast Cancer... Human Papilloma Virus in Breast Cancer 5b. GRANT NUMBER 1 H 11 1 06 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Betty Diamond 5d. PROJECT...virus (EBV), Hepatitis B Virus (HBV), Hepatitis C virus (HCV), Human Papilloma virus (HPV), Human T-cell lymphotropic virus (HTLV-1) and Kaposi’s

  9. Computed tomography urography in non malignant kidney diseases – how to overcome one of the disadvantages?

    International Nuclear Information System (INIS)

    Al-Amin, M.

    2013-01-01

    Full text: Introduction: Computed tomography urography is among the fastest growing imaging directions, indications of which continue to change. Radiation dose is one of its main disadvantages. There are a number of literary publications regarding how to reduce radiation dose: by voltage, by mA or by reducing the number of phases. What you will learn: We present the initial experience in the diagnosis of non-malignant kidney disease with three low-dose study protocol: a standard low dose, low dose and low dose introduced by us. Our research is based on three groups of patients. The first of 36 men and 22 women viewed with repetitive low-dose protocol: 120 kV / 219 effective milliampere. The second and third group of 16 men and 9 women, respectively: 100/ 163 and 80/115 . Discussion: There have been a number of studies to reduce the radiation dose that is considered one of the main disadvantages of computed tomography urography. Reducing mA (≤ 30 mAs), leads to the radiation dose similar to that of an overview abdominal radiography. Reducing of 140 kV to 120, reducing the dosage of the skin by about 33 % and decreasing it to 80 kilovolts, the result is about 70 %. Another technology to reduce radiation exposure is by reducing the number of phases of the study, but studies have shown that the removal of the native phase is not desirable. Conclusion: We believe that computed tomography urography is a detailed study that should be applied in certain clinical indications. Its major disadvantage is the radiation dose. Images obtained with low-dose protocols are newly comparable image quality to the standard, but with much lower radiation exposure

  10. Fulvestrant radiosensitizes human estrogen receptor-positive breast cancer cells

    International Nuclear Information System (INIS)

    Wang, Jing; Yang, Qifeng; Haffty, Bruce G.; Li, Xiaoyan; Moran, Meena S.

    2013-01-01

    Highlights: ► Fulvestrant radiosensitizes MCF-7 cells. ► Fulvestrant increases G1 arrest and decreases S phase in MCF-7 cells. ► Fulvestrant down-regulates DNA-PKcs and RAD51 in MCF-7 cells. -- Abstract: The optimal sequencing for hormonal therapy and radiation are yet to be determined. We utilized fulvestrant, which is showing promise as an alternative to other agents in the clinical setting of hormonal therapy, to assess the cellular effects of concomitant anti-estrogen therapy (fulvestrant) with radiation (F + RT). This study was conducted to assess the effects of fulvestrant alone vs. F + RT on hormone-receptor positive breast cancer to determine if any positive or negative combined effects exist. The effects of F + RT on human breast cancer cells were assessed using MCF-7 clonogenic and tetrazolium salt colorimetric (MTT) assays. The assays were irradiated with a dose of 0, 2, 4, 6 Gy ± fulvestrant. The effects of F + RT vs. single adjuvant treatment alone on cell-cycle distribution were assessed using flow cytometry; relative expression of repair proteins (Ku70, Ku80, DNA-PKcs, Rad51) was assessed using Western Blot analysis. Cell growth for radiation alone vs. F + RT was 0.885 ± 0.013 vs. 0.622 ± 0.029 @2 Gy, 0.599 ± 0.045 vs. 0.475 ± 0.054 @4 Gy, and 0.472 ± 0.021 vs. 0.380 ± 0.018 @6 Gy RT (p = 0.003). While irradiation alone induced G2/M cell cycle arrest, the combination of F + RT induced cell redistribution in the G1 phase and produced a significant decrease in the proportion of cells in G2 phase arrest and in the S phase in breast cancer cells (p < 0.01). Furthermore, levels of repair proteins DNA-PKcs and Rad51 were significantly decreased in the cells treated with F + RT compared with irradiation alone. F + RT leads to a decrease in the surviving fraction, increased cell cycle arrest, down regulating of nonhomologous repair protein DNA-PKcs and homologous recombination repair protein RAD51. Thus, our findings suggest that F + RT

  11. The effect of between-breast differences on human milk macronutrients content.

    Science.gov (United States)

    Pines, N; Mandel, D; Mimouni, F B; Moran Lev, H; Mangel, L; Lubetzky, R

    2016-07-01

    Little is known about the effect of maternal handedness and preferential side of breastfeeding upon macronutrients concentration in human milk (HM). We aimed to compare macronutrients content of HM from both breasts, taking into account the self-reported preferential feeding ('dominant') breast, breast size and handedness (right versus left). We tested the null hypothesis that macronutrients content of HM is not affected by breast dominancy, breast size or maternal handedness. Fifty-seven lactating mothers were recruited. HM macronutrients were measured after mid manual expression using infrared transmission spectroscopy. Out of the 57 mothers recruited, 12 were excluded from the analyses because they brought in insufficient samples. Among the 22 who reported a size difference, 16 (73%) had a larger left breast (Pmacronutrients between the right and the left breasts. In multiple stepwise backward regression analysis, fat, carbohydrate, protein and energy contents were unaffected by maternal handedness, breast side dominance or breast size asymmetry. Macronutrients content of mid expression HM is unaffected by maternal handedness, breast size or breast side dominance.

  12. Raman spectroscopy and imaging: applications in human breast cancer diagnosis.

    Science.gov (United States)

    Brozek-Pluska, Beata; Musial, Jacek; Kordek, Radzislaw; Bailo, Elena; Dieing, Thomas; Abramczyk, Halina

    2012-08-21

    The applications of spectroscopic methods in cancer detection open new possibilities in early stage diagnostics. Raman spectroscopy and Raman imaging represent novel and rapidly developing tools in cancer diagnosis. In the study described in this paper Raman spectroscopy has been employed to examine noncancerous and cancerous human breast tissues of the same patient. The most significant differences between noncancerous and cancerous tissues were found in regions characteristic for the vibrations of carotenoids, lipids and proteins. Particular attention was paid to the role played by unsaturated fatty acids in the differentiation between the noncancerous and the cancerous tissues. Comparison of Raman spectra of the noncancerous and the cancerous tissues with the spectra of oleic, linoleic, α-linolenic, γ-linolenic, docosahexaenoic and eicosapentaenoic acids has been presented. The role of sample preparation in the determination of cancer markers is also discussed in this study.

  13. Mechanical response of human female breast skin under uniaxial stretching.

    Science.gov (United States)

    Kumaraswamy, N; Khatam, Hamed; Reece, Gregory P; Fingeret, Michelle C; Markey, Mia K; Ravi-Chandar, Krishnaswamy

    2017-10-01

    Skin is a complex material covering the entire surface of the human body. Studying the mechanical properties of skin to calibrate a constitutive model is of great importance to many applications such as plastic or cosmetic surgery and treatment of skin-based diseases like decubitus ulcers. The main objective of the present study was to identify and calibrate an appropriate material constitutive model for skin and establish certain universal properties that are independent of patient-specific variability. We performed uniaxial tests performed on breast skin specimens freshly harvested during mastectomy. Two different constitutive models - one phenomenological and another microstructurally inspired - were used to interpret the mechanical responses observed in the experiments. Remarkably, we found that the model parameters that characterize dependence on previous maximum stretch (or preconditioning) exhibited specimen-independent universal behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Low-risk susceptibility alleles in 40 human breast cancer cell lines

    International Nuclear Information System (INIS)

    Riaz, Muhammad; Elstrodt, Fons; Hollestelle, Antoinette; Dehghan, Abbas; Klijn, Jan GM; Schutte, Mieke

    2009-01-01

    Low-risk breast cancer susceptibility alleles or SNPs confer only modest breast cancer risks ranging from just over 1.0 to1.3 fold. Yet, they are common among most populations and therefore are involved in the development of essentially all breast cancers. The mechanism by which the low-risk SNPs confer breast cancer risks is currently unclear. The breast cancer association consortium BCAC has hypothesized that the low-risk SNPs modulate expression levels of nearby located genes. Genotypes of five low-risk SNPs were determined for 40 human breast cancer cell lines, by direct sequencing of PCR-amplified genomic templates. We have analyzed expression of the four genes that are located nearby the low-risk SNPs, by using real-time RT-PCR and Human Exon microarrays. The SNP genotypes and additional phenotypic data on the breast cancer cell lines are presented. We did not detect any effect of the SNP genotypes on expression levels of the nearby-located genes MAP3K1, FGFR2, TNRC9 and LSP1. The SNP genotypes provide a base line for functional studies in a well-characterized cohort of 40 human breast cancer cell lines. Our expression analyses suggest that a putative disease mechanism through gene expression modulation is not operative in breast cancer cell lines

  15. 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

    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......: 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 primary end point was time to progression. RESULTS: We randomly assigned 78 patients to capecitabine and 78 patients to capecitabine plus trastuzumab. Sixty-five events and 38 deaths in the capecitabine group and 62 events and 33 deaths in the capecitabine-plus-trastuzumab group occurred during 15...

  16. Identification of differentially expressed microRNAs in human male breast cancer

    Directory of Open Access Journals (Sweden)

    Schipper Elisa

    2010-03-01

    Full Text Available Abstract Background The discovery of small non-coding RNAs and the subsequent analysis of microRNA expression patterns in human cancer specimens have provided completely new insights into cancer biology. Genetic and epigenetic data indicate oncogenic or tumor suppressor function of these pleiotropic regulators. Therefore, many studies analyzed the expression and function of microRNA in human breast cancer, the most frequent malignancy in females. However, nothing is known so far about microRNA expression in male breast cancer, accounting for approximately 1% of all breast cancer cases. Methods The expression of 319 microRNAs was analyzed in 9 primary human male breast tumors and in epithelial cells from 15 male gynecomastia specimens using fluorescence-labeled bead technology. For identification of differentially expressed microRNAs data were analyzed by cluster analysis and selected statistical methods. Expression levels were validated for the most up- or down-regulated microRNAs in this training cohort using real-time PCR methodology as well as in an independent test cohort comprising 12 cases of human male breast cancer. Results Unsupervised cluster analysis separated very well male breast cancer samples and control specimens according to their microRNA expression pattern indicating cancer-specific alterations of microRNA expression in human male breast cancer. miR-21, miR519d, miR-183, miR-197, and miR-493-5p were identified as most prominently up-regulated, miR-145 and miR-497 as most prominently down-regulated in male breast cancer. Conclusions Male breast cancer displays several differentially expressed microRNAs. Not all of them are shared with breast cancer biopsies from female patients indicating male breast cancer specific alterations of microRNA expression.

  17. Gene expression analysis in human breast cancer associated blood vessels.

    Directory of Open Access Journals (Sweden)

    Dylan T Jones

    Full Text Available Angiogenesis is essential for solid tumour growth, whilst the molecular profiles of tumour blood vessels have been reported to be different between cancer types. Although presently available anti-angiogenic strategies are providing some promise for the treatment of some cancers it is perhaps not surprisingly that, none of the anti-angiogenic agents available work on all tumours. Thus, the discovery of novel anti-angiogenic targets, relevant to individual cancer types, is required. Using Affymetrix microarray analysis of laser-captured, CD31-positive blood vessels we have identified 63 genes that are upregulated significantly (5-72 fold in angiogenic blood vessels associated with human invasive ductal carcinoma (IDC of the breast as compared with blood vessels in normal human breast. We tested the angiogenic capacity of a subset of these genes. Genes were selected based on either their known cellular functions, their enriched expression in endothelial cells and/or their sensitivity to anti-VEGF treatment; all features implicating their involvement in angiogenesis. For example, RRM2, a ribonucleotide reductase involved in DNA synthesis, was upregulated 32-fold in IDC-associated blood vessels; ATF1, a nuclear activating transcription factor involved in cellular growth and survival was upregulated 23-fold in IDC-associated blood vessels and HEX-B, a hexosaminidase involved in the breakdown of GM2 gangliosides, was upregulated 8-fold in IDC-associated blood vessels. Furthermore, in silico analysis confirmed that AFT1 and HEX-B also were enriched in endothelial cells when compared with non-endothelial cells. None of these genes have been reported previously to be involved in neovascularisation. However, our data establish that siRNA depletion of Rrm2, Atf1 or Hex-B had significant anti-angiogenic effects in VEGF-stimulated ex vivo mouse aortic ring assays. Overall, our results provide proof-of-principle that our approach can identify a cohort of

  18. Anti-complement activities of human breast-milk.

    Science.gov (United States)

    Ogundele, M O

    1999-08-01

    It has long been observed that the human milk possesses significant anti-inflammatory properties, while simultaneously protecting the infant against many intestinal and respiratory pathogens. There is, however, a paucity of information on the degree and extent of this anti-inflammatory activity. In the present study, the inhibitory effects of different fractions of human milk on serum complement activity were analysed. Colostrum and milk samples from healthy voluntary lactating donors at different postpartum ages were obtained and pooled normal human serum was used as source of complement in a modified CH50 assay. Inherent complement activity in human milk was also investigated by measuring the deposition of an activated C3 fragment on a serum-sensitive bacteria, and by haemolytic assays. Most whole- and defatted-milk samples consistently showed a dose-dependent inhibition of the serum complement activity. This inhibition was greater in mature milk compared to transitional milk samples. It was enhanced by inactivation of milk complement, and diminished by centrifugation of milk samples, which partly removed fat and larger protein components including casein micelles. Inherent complement activity in human milk was also demonstrated by haemolysis of sensitised sheep erythrocytes and deposition of C3 fragments on solid-phase bacteria. These activities were highest in the colostrum and gradually decreased as lactation proceeded. Several natural components abundant in the fluid phase of the human breast-milk have been shown to be inhibitors of complement activation in vitro. Their physiological significance probably reside in their ability to prevent inflammatory-induced tissue damage of the delicate immature gastrointestinal tract of the new-born as well as the mammary gland itself, which may arise from ongoing complement activation.

  19. Persistent organochlorines in human breast milk collected from primiparae in Dalian and Shenyang, China

    International Nuclear Information System (INIS)

    Kunisue, Tatsuya; Someya, Masayuki; Kayama, Fujio; Jin Yihe; Tanabe, Shinsuke

    2004-01-01

    The present study determined the concentrations of organochlorines (OCs) such as polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane and its metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), chlordane compounds (CHLs), hexachlorobenzene (HCB) and tris(4-chlorophenyl)methane (TCPMe) in human breast milk collected from primiparae in Dalian and Shenyang, northeastern China during 2002. In addition, dioxins and related compounds in pooled samples of human breast milk from Dalian and Shenyang were also analyzed. OCs were detected in all the human breast milk samples analyzed in this study. The predominant contaminants in human breast milk were HCHs, DDTs and HCB, and the levels were relatively higher than those in other countries. On the other hand, concentrations of dioxins and related compounds, PCBs, and CHLs were relatively low. Concentrations of OCs in human breast milk from Dalian, which is located along the coast of Bo Hai Strait, were significantly higher than those from Shenyang, implying that the residents in Dalian might be mainly exposed to these contaminants from seafood. When the relationship between concentrations of OCs in human breast milk and age of primiparae was examined, no significant correlation was observed. This might be caused by the limited sample numbers and narrow range of mother's age and/or recent ban of DDT and HCH production and use. Significant correlation between concentrations of TCPMe and DDTs in human breast milk suggested that technical DDT might be a source of TCPMe in the Chinese population. When daily intakes of DDTs and HCHs to infants through human breast milk were estimated, human breast milk from Dalian showed significantly higher contribution than Shenyang, implying that infants in Dalian might be at higher risk by these contaminants

  20. B-cell lymphoma 6 protein stimulates oncogenicity of human breast cancer cells

    International Nuclear Information System (INIS)

    Wu, Qiang; Kong, Xiang-jun; Xu, Xiao-chun; Lobie, Peter E; Zhu, Tao; Wu, Zheng-sheng; Liu, Xue; Yan, Hong; He, Yin-huan; Ye, Shan; Cheng, Xing-wang; Zhu, Gui-lu; Wu, Wen-yong; Wang, Xiao-nan

    2014-01-01

    B-cell lymphoma 6 (BCL6) protein, an evolutionarily conserved zinc finger transcription factor, showed to be highly expressed in various human cancers in addition to malignancies in the lymphoid system. This study investigated the role of BCL6 expression in breast cancer and its clinical significance in breast cancer patients. Expression of BCL6 protein was assessed using in situ hybridization and immunohistochemistry in 127 breast cancer patients and 50 patients with breast benign disease as well as in breast cell lines. Expression of BCL6 was restored or knocked down in two breast cancer cell lines (MCF-7 and T47D) using BCL6 cDNA and siRNA, respectively. The phenotypic change of these breast cancer cell lines was assessed using cell viability MTT, Transwell invasion, colony formation, and flow cytometry assays and in a xenograft mice model. Luciferase reporter gene, immunoblot, and qRT-PCR were used to investigate the molecular events after manipulated BCL6 expression in breast cancer cells. BCL6 protein was highly expressed in breast cancer cell lines and tissue specimens and expression of BCL6 protein was associated with disease progression and poor survival of breast cancer patients. In vitro, the forced expression of BCL6 results in increased proliferation, anchorage-independent growth, migration, invasion and survival of breast cancer cell lines, whereas knockdown of BCL6 expression reduced these oncogenic properties of breast cancer cells. Moreover, forced expression of BCL6 increased tumor growth and invasiveness in a nude mouse xenograft model. At the gene level, BCL6 was a target gene of miR-339-5p. Expression of BCL6 induced expression of CXCR4 and cyclinD1 proteins. The current study demonstrated the oncogenic property of BCL6 in breast cancer and further study could target BCL6 as a novel potential therapeutic strategy for breast cancer

  1. Gastrin-releasing peptide receptor imaging in human breast carcinoma versus immunohistochemistry

    NARCIS (Netherlands)

    de Wiele, Christophe Van; Phonteyne, Philippe; Pauwels, Patrick; Goethals, Ingeborg; Van den Broecke, Rudi; Cocquyt, Veronique; Dierckx, Rudi Andre

    This study reports on the uptake of (99m)Tc-RP527 by human breast carcinoma and its relationship to gastrin-releasing peptide receptor (GRIP-R) expression as measured by immunohistochemistry (IHC). Methods: Nine patients referred because of a clinical diagnosis suggestive of breast carcinoma and 5

  2. Automated quantification of aligned collagen for human breast carcinoma prognosis

    Directory of Open Access Journals (Sweden)

    Jeremy S Bredfeldt

    2014-01-01

    Full Text Available Background: Mortality in cancer patients is directly attributable to the ability of cancer cells to metastasize to distant sites from the primary tumor. This migration of tumor cells begins with a remodeling of the local tumor microenvironment, including changes to the extracellular matrix and the recruitment of stromal cells, both of which facilitate invasion of tumor cells into the bloodstream. In breast cancer, it has been proposed that the alignment of collagen fibers surrounding tumor epithelial cells can serve as a quantitative image-based biomarker for survival of invasive ductal carcinoma patients. Specific types of collagen alignment have been identified for their prognostic value and now these tumor associated collagen signatures (TACS are central to several clinical specimen imaging trials. Here, we implement the semi-automated acquisition and analysis of this TACS candidate biomarker and demonstrate a protocol that will allow consistent scoring to be performed throughout large patient cohorts. Methods: Using large field of view high resolution microscopy techniques, image processing and supervised learning methods, we are able to quantify and score features of collagen fiber alignment with respect to adjacent tumor-stromal boundaries. Results: Our semi-automated technique produced scores that have statistically significant correlation with scores generated by a panel of three human observers. In addition, our system generated classification scores that accurately predicted survival in a cohort of 196 breast cancer patients. Feature rank analysis reveals that TACS positive fibers are more well-aligned with each other, are of generally lower density, and terminate within or near groups of epithelial cells at larger angles of interaction. Conclusion: These results demonstrate the utility of a supervised learning protocol for streamlining the analysis of collagen alignment with respect to tumor stromal boundaries.

  3. Potential Angiogenic Role of Platelet-Activating Factor in Human Breast Cancer

    Science.gov (United States)

    Montrucchio, Giuseppe; Sapino, Anna; Bussolati, Benedetta; Ghisolfi, Gianpiero; Rizea-Savu, Simona; Silvestro, Luigi; Lupia, Enrico; Camussi, Giovanni

    1998-01-01

    This study investigated the presence of platelet-activating factor (PAF) in the lipid extracts of 18 primary breast carcinomas and 20 control breast tissues. The amount of PAF detected in breast carcinomas was significantly higher than in controls. The mass spectrometric analysis of PAF-bioactive lipid extract from breast carcinomas showed the presence of several molecular species of PAF, including C16-alkylPAF, C18-lysophosphatidylcholine (LPC), C16-LPC, lyso-PAF, and C16-acylPAF. The amount of bioactive PAF extracted from breast specimens significantly correlated with tumor vascularization revealed by the number of CD34- and CD31-positive cells. As C16-alkylPAF was previously shown to induce angiogenesis in vivo, we evaluated whether the thin layer chromatography-purified lipid extracts of breast specimens elicited neoangiogenesis in a murine model of subcutaneous Matrigel injection. The lipid extracts from specimens of breast carcinoma containing high levels of PAF bioactivity, but not from breast carcinomas containing low levels of PAF bioactivity or from normal breast tissue, induced a significant angiogenic response. This angiogenic response was significantly inhibited by the PAF receptor antagonist WEB 2170. T47D and MCF7 breast cancer cell lines, but not an immortalized nontumor breast cell line (MCF10), released PAF in the culture medium. A significant in vivo neoangiogenic response, inhibited by WEB 2170, was elicited by T47D and MCF7 but not by MCF10 culture medium. These results indicate that an increased concentration of PAF is present in tumors with high microvessel density and that PAF may account for the neoangiogenic activity induced in mice by the lipid extracts obtained from breast cancer. A contribution of PAF in the neovascularization of human breast cancer is suggested. PMID:9811351

  4. A Role for the NF-kb/Rel Transcription Factors in Human Breast Cancer

    National Research Council Canada - National Science Library

    Baldwin, Albert

    1998-01-01

    Human breast cancer is characterized by the inappropriate expression of growth factors, kinases and possibly certain transcription factors Our project has focused on the regulation of the NF-kB family...

  5. Role of Notch Signaling in Human Breast Cancer Pathogenesis

    Science.gov (United States)

    2006-11-01

    transform HMLE cells. Similarly, overexpression of ErbB2, a receptor tyrosine kinase upstream of Ras normally found overexpressed in many breast cancers ...Assess Notch-Ras cooperation in breast cancers in vivo: Since the major observation in this project has been the cooperation of Notch and Ras in HMLE ...metastasis. The in vitro cooperation between Notch and Ras in HMLE cells is mimicked in naturally arising breast cancers in vivo. Further dissection of the

  6. Human Papilloma Virus Identification in Breast Cancer Patients with Previous Cervical Neoplasia.

    Science.gov (United States)

    Lawson, James S; Glenn, Wendy K; Salyakina, Daria; Clay, Rosemary; Delprado, Warick; Cheerala, Bharathi; Tran, Dinh D; Ngan, Christopher C; Miyauchi, Shingo; Karim, Martha; Antonsson, Annika; Whitaker, Noel J

    2015-01-01

    Women with human papilloma virus (HPV)-associated cervical neoplasia have a higher risk of developing breast cancer than the general female population. The purpose of this study was to (i) identify high-risk HPVs in cervical neoplasia and subsequent HPV positive breast cancers which developed in the same patients and (ii) determine if these HPVs were biologically active. A range of polymerase chain reaction and immunohistochemical techniques were used to conduct a retrospective cohort study of cervical precancers and subsequent breast cancers in the same patients. The same high-risk HPV types were identified in both the cervical and breast specimens in 13 (46%) of 28 patients. HPV type 18 was the most prevalent. HPVs appeared to be biologically active as demonstrated by the expression of HPV E7 proteins and the presence of HPV-associated koilocytes. The average age of these patients diagnosed with breast cancer following prior cervical precancer was 51 years, as compared to 60 years for all women with breast cancer (p for difference = 0.001). These findings indicate that high-risk HPVs can be associated with cervical neoplasia and subsequent young age breast cancer. However, these associations are unusual and are a very small proportion of breast cancers. These outcomes confirm and extend the observations of two similar previous studies and offer one explanation for the increased prevalence of serious invasive breast cancer among young women.

  7. Human papilloma virus identification in breast cancer patients with previous cervical neoplasia

    Directory of Open Access Journals (Sweden)

    James Sutherland Lawson

    2016-01-01

    Full Text Available Purpose: Women with human papilloma virus (HPV associated cervical neoplasia have a higher risk of developing breast cancer than the general female population. The purpose of this study was to (i identify high risk for cancer HPVs in cervical neoplasia and subsequent HPV positive breast cancers which developed in the same patients and (ii determine if these HPVs were biologically active.Methods: A range of polymerase chain reaction (PCR and immunohistochemical techniques were used to conduct a retrospective cohort study of cervical precancers and subsequent breast cancers in the same patients. Results: The same high risk HPV types were identified in both the cervical and breast specimens in 13 (46% of 28 patients. HPV type 18 was the most prevalent. HPVs appeared to be biologically active as demonstrated by the expression of HPV E7 proteins and the presence of HPV associated koilocytes. The average age of these patients diagnosed with breast cancer following prior cervical precancer was 51 years, as compared to 60 years for all women with breast cancer (p for difference = 0.001. Conclusions: These findings indicate that high risk HPVs can be associated with cervical neoplasia and subsequent young age breast cancer. However these associations are unusual and are a very small proportion of breast cancers. These outcomes confirm and extend the observations of 2 similar previous studies and offer one explanation for the increased prevalence of serious invasive breast cancer among young women.

  8. Vav3 oncogene activates estrogen receptor and its overexpression may be involved in human breast cancer

    International Nuclear Information System (INIS)

    Lee, Kiwon; Liu, Yin; Mo, Jun Qin; Zhang, Jinsong; Dong, Zhongyun; Lu, Shan

    2008-01-01

    Our previous study revealed that Vav3 oncogene is overexpressed in human prostate cancer, activates androgen receptor, and stimulates growth in prostate cancer cells. The current study is to determine a potential role of Vav3 oncogene in human breast cancer and impact on estrogen receptor a (ERα)-mediated signaling axis. Immunohistochemistry analysis was performed in 43 breast cancer specimens and western blot analysis was used for human breast cancer cell lines to determine the expression level of Vav3 protein. The impact of Vav3 on breast cancer cell growth was determined by siRNA knockdown of Vav3 expression. The role of Vav3 in ERα activation was examined in luciferase reporter assays. Deletion mutation analysis of Vav3 protein was performed to localize the functional domain involved in ERα activation. Finally, the interaction of Vav3 and ERα was assessed by GST pull-down analysis. We found that Vav3 was overexpressed in 81% of human breast cancer specimens, particularly in poorly differentiated lesions. Vav3 activated ERα partially via PI3K-Akt signaling and stimulated growth of breast cancer cells. Vav3 also potentiated EGF activity for cell growth and ERα activation in breast cancer cells. More interestingly, we found that Vav3 complexed with ERα. Consistent with its function for AR, the DH domain of Vav3 was essential for ERα activation. Vav3 oncogene is overexpressed in human breast cancer. Vav3 complexes with ERα and enhances ERα activity. These findings suggest that Vav3 overexpression may aberrantly enhance ERα-mediated signaling axis and play a role in breast cancer development and/or progression

  9. Ceramide species are elevated in human breast cancer and are associated with less aggressiveness

    Science.gov (United States)

    Moro, Kazuki; Kawaguchi, Tsutomu; Tsuchida, Junko; Gabriel, Emmanuel; Qi, Qianya; Yan, Li; Wakai, Toshifumi; Takabe, Kazuaki; Nagahashi, Masayuki

    2018-01-01

    Sphingolipids have emerged as key regulatory molecules in cancer cell survival and death. Although important roles of sphingolipids in breast cancer progression have been reported in experimental models, their roles in human patients are yet to be revealed. The aim of this study was to investigate the ceramide levels and its biosynthesis pathways in human breast cancer patients. Breast cancer, peri-tumor and normal breast tissue samples were collected from surgical specimens from a series of 44 patients with breast cancer. The amount of sphingolipid metabolites in the tissue were determined by mass spectrometry. The Cancer Genome Atlas was used to analyze gene expression related to the sphingolipid metabolism. Ceramide levels were higher in breast cancer tissue compared to both normal and peri-tumor breast tissue. Substrates and enzymes that generate ceramide were significantly increased in all three ceramide biosynthesis pathways in cancer. Further, higher levels of ceramide in breast cancer were associated with less aggressive cancer biology presented by Ki-67 index and nuclear grade of the cancer. Interestingly, patients with higher gene expressions of enzymes in the three major ceramide synthesis pathways showed significantly worse prognosis. This is the first study to reveal the clinical relevance of ceramide metabolism in breast cancer patients. We demonstrated that ceramide levels in breast cancer tissue were significantly higher than those in normal tissue, with activation of the three ceramide biosynthesis pathways. We also identified that ceramide levels have a significant association with aggressive phenotype and its enzymes have prognostic impact on breast cancer patients. PMID:29731990

  10. Meta-ethnography to understand healthcare professionals’ experience of treating adults with chronic non-malignant pain

    Science.gov (United States)

    Seers, Kate; Barker, Karen L

    2017-01-01

    Objectives We aimed to explore healthcare professionals’ experience of treating chronic non-malignant pain by conducting a qualitative evidence synthesis. Understanding this experience from the perspective of healthcare professionals will contribute to improvements in the provision of care. Design Qualitative evidence synthesis using meta-ethnography. We searched five electronic bibliographic databases from inception to November 2016. We included studies that explore healthcare professionals’ experience of treating adults with chronic non-malignant pain. We used the GRADE-CERQual framework to rate confidence in review findings. Results We screened the 954 abstracts and 184 full texts and included 77 published studies reporting the experiences of over 1551 international healthcare professionals including doctors, nurses and other health professionals. We abstracted six themes: (1) a sceptical cultural lens, (2) navigating juxtaposed models of medicine, (3) navigating the geography between patient and clinician, (4) challenge of dual advocacy, (5) personal costs and (6) the craft of pain management. We rated confidence in review findings as moderate to high. Conclusions This is the first qualitative evidence synthesis of healthcare professionals’ experiences of treating people with chronic non-malignant pain. We have presented a model that we developed to help healthcare professionals to understand, think about and modify their experiences of treating patients with chronic pain. Our findings highlight scepticism about chronic pain that might explain why patients feel they are not believed. Findings also indicate a dualism in the biopsychosocial model and the complexity of navigating therapeutic relationships. Our model may be transferable to other patient groups or situations. PMID:29273663

  11. Overexpression of peroxiredoxin I and thioredoxin1 in human breast carcinoma

    Directory of Open Access Journals (Sweden)

    Kim Il-Han

    2009-06-01

    Full Text Available Abstract Background Peroxiredoxins (Prxs are a novel group of peroxidases containing high antioxidant efficiency. The mammalian Prx family has six distinct members (Prx I-VI in various subcellular locations, including peroxisomes and mitochondria, places where oxidative stress is most evident. The function of Prx I in particular has been implicated in regulating cell proliferation, differentiation, and apoptosis. Since thioredoxin1 (Trx1 as an electron donor is functionally associated with Prx I, we investigated levels of expression of both Prx I and Trx1. Methods We investigated levels of expression of both Prx I and Trx1 in breast cancer by real-time polymerase chain reaction (RT-PCR and Western blot. Results Levels of messenger RNA (mRNA for both Prx I and Trx1 in normal human breast tissue were very low compared to other major human tissues, whereas their levels in breast cancer exceeded that in other solid cancers (colon, kidney, liver, lung, ovary, prostate, and thyroid. Among members of the Prx family (Prx I-VI and Trx family (Trx1, Trx2, Prx I and Trx1 were preferentially induced in breast cancer. Moreover, the expression of each was associated with progress of breast cancer and correlated with each other. Western blot analysis of different and paired breast tissues revealed consistent and preferential expression of Prx I and Trx1 protein in breast cancer tissue. Conclusion Prx I and Trx1 are overexpressed in human breast carcinoma and the expression levels are associated with tumor grade. The striking induction of Prx I and Trx1 in breast cancer may enable their use as breast cancer markers.

  12. Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche.

    Science.gov (United States)

    Templeton, Zach S; Lie, Wen-Rong; Wang, Weiqi; Rosenberg-Hasson, Yael; Alluri, Rajiv V; Tamaresis, John S; Bachmann, Michael H; Lee, Kitty; Maloney, William J; Contag, Christopher H; King, Bonnie L

    2015-12-01

    Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein) and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014) and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006) and IL-1β (P = .001) in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  13. A mega-ethnography of eleven qualitative evidence syntheses exploring the experience of living with chronic non-malignant pain.

    Science.gov (United States)

    Toye, Fran; Seers, Kate; Hannink, Erin; Barker, Karen

    2017-08-01

    Each year over five million people develop chronic non-malignant pain and can experience healthcare as an adversarial struggle. The aims of this study were: (1) to bring together qualitative evidence syntheses that explore patients' experience of living with chronic non-malignant pain and develop conceptual understanding of what it is like to live with chronic non-malignant pain for improved healthcare; (2) to undertake the first mega-ethnography of qualitative evidence syntheses using the methods of meta-ethnography. We used the seven stages of meta-ethnography refined for large studies. The innovation of mega-ethnography is to use conceptual findings from qualitative evidence syntheses as primary data. We searched 7 bibliographic databases from inception until February 2016 to identify qualitative evidence syntheses that explored patients' experience of living with chronic non-malignant pain. We identified 82 potential studies from 556 titles, screened 34 full text articles and included 11 qualitative evidence syntheses synthesising a total of 187 qualitative studies reporting more than 5000 international participants living with chronic pain. We abstracted concepts into 7 conceptual categories: (1) my life is impoverished and confined; (2) struggling against my body to be me; (3) the quest for the diagnostic 'holy grail'; (4) lost personal credibility; (5) trying to keep up appearances; (6) need to be treated with dignity; and (7) deciding to end the quest for the grail is not easy. Each conceptual category was supported by at least 7 of the 11 qualitative evidence syntheses. This is the first mega-ethnography, or synthesis of qualitative evidence syntheses using the methods of meta-ethnography. Findings help us to understand that the decision to end the quest for a diagnosis can leave patients feeling vulnerable and this may contribute to the adversarial nature of the clinical encounter. This knowledge demonstrates that treating a patient with a sense that they

  14. Pharmacological consequences of long-term morphine treatment in patients with cancer and chronic non-malignant pain

    DEFF Research Database (Denmark)

    Andersen, Gertrud; Sjøgren, Per; Hansen, Steen Honoré

    2004-01-01

    In patients with pain of malignant origin morphine may be administered in high and often increasing doses during extended periods of time. In patients with chronic pain of non-malignant origin morphine may be an important remedy, and in these cases the goal is to keep the morphine dose stable. Th....... The pharmacokinetic as well as the pharmacodynamic consequences of long-term morphine treatment with special reference to the two most important metabolites of morphine morphine-6-glucuronide (M-6-G) and morphine-3-glucuronide (M-3-G) remain to be settled....

  15. Quantitation of human immunodeficiency virus type 1 in breast milk.

    Science.gov (United States)

    Ghosh, M K; Kuhn, L; West, J; Semrau, K; Decker, D; Thea, D M; Aldrovandi, G M

    2003-06-01

    The distribution and stability of human immunodeficiency virus type 1 (HIV-1) in breast milk (BM) components remain largely unknown. Inhibitory effects, if any, of BM on HIV RNA and DNA PCR amplification are poorly understood. We have addressed these issues by using virus-spiked BM samples from HIV-negative women. BM samples from HIV-negative women were spiked with HIV-1 virions or cells containing a single integrated copy of HIV DNA (8E5/LAV). After incubation under different experimental conditions, viral RNA was detected by the Roche Amplicor UltraSensitive assay in whole-milk, skim milk, and lipid fractions. We found excellent correlation between HIV-1 input copy and recovery in whole milk (r = 0.965, P milk (r = 0.972, P 0.982). The effects of incubation duration and temperature and repeated freeze-thaw cycles on HIV RNA recovery were analyzed. HIV RNA levels were remarkably stable in whole milk after three freeze-thaw cycles and for up to 30 h at room temperature. Our findings improve the understanding of the dynamics of HIV detection in BM and the conditions for BM sample collection, storage, and processing.

  16. Nonexpansive immediate breast reconstruction using human acellular tissue matrix graft (AlloDerm).

    Science.gov (United States)

    Salzberg, C Andrew

    2006-07-01

    Immediate breast reconstruction has become a standard of care following mastectomy for cancer, largely due to improved esthetic and psychologic outcomes achieved with this technique. However, the current historical standards--transverse rectus abdominis myocutaneous flap reconstruction and expander--implant surgery-still have limitations as regards patient morbidity, short-term body-image improvements, and even cost. To address these shortcomings, we employ a novel concept of human tissue replacement to enhance breast shape and provide total coverage, enabling immediate mound reconstruction without the need for breast expansion prior to permanent implant placement. AlloDerm (human acellular tissue matrix) is a human-derived graft tissue with extensive experience in various settings of skin and soft tissue replacement surgery. This report describes the success using acellular tissue matrix to provide total coverage over the prosthesis in immediate reconstruction, with limited muscle dissection. In this population, 49 patients (76 breasts) successfully underwent the acellular tissue matrix-based immediate reconstruction, resulting in durable breast reconstruction with good symmetry. These findings may predict that acellular tissue matrix-supplemented immediate breast reconstruction will become a new technique for the immediate reconstruction of the postmastectomy breast.

  17. Persistent Pesticides in Human Breast Milk and Cryptorchidism

    Science.gov (United States)

    Damgaard, Ida N.; Skakkebæk, Niels E.; Toppari, Jorma; Virtanen, Helena E.; Shen, Heqing; Schramm, Karl-Werner; Petersen, Jørgen H.; Jensen, Tina K.; Main, Katharina M.

    2006-01-01

    Introduction Prenatal exposure to some pesticides can adversely affect male reproductive health in animals. We investigated a possible human association between maternal exposure to 27 organochlorine compounds used as pesticides and cryptorchidism among male children. Design Within a prospective birth cohort, we performed a case–control study; 62 milk samples from mothers of cryptorchid boys and 68 from mothers of healthy boys were selected. Milk was collected as individual pools between 1 and 3 months postpartum and analyzed for 27 organochlorine pesticides. Results Eight organochlorine pesticides were measurable in all samples (medians; nanograms per gram lipid) for cases/controls: 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (p,p′-DDE): 97.3/83.8; β-hexachlorocyclohexane (β-HCH): 13.6/12.3; hexachlorobenzene (HCB): 10.6/8.8; α -endosulfan: 7.0/6.7; oxychlordane: 4.5/4.1; 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p,p′-DDT): 4.6/4.0; dieldrin: 4.1/3.1; cis-heptachloroepoxide (cis-HE): 2.5/2.2. Five compounds [octachlorostyrene (OCS); pentachlorobenzene, 1,1-dichloro-2,2-bis(4-chlorophenyl)ethane (p,p′-DDD); o,p′-DDT; mirex] were measurable in most samples (detection rates 90.8–99.2%) but in lower concentrations. For methoxychlor, cis-chlordane, pentachloroanisole (PCA), γ -HCH, 1,1-dichloro-2-(2-chlorophenyl)-2,2(4-chlorophenyl)ethane, trans-chlordane, α -HCH, and o,p′-DDE, both concentrations and detection rates were low (26.5–71.5%). Heptachlor, HCH (δ, ɛ ), aldrin, β-endosulfan and trans-heptachloroepoxide were detected at negligible concentrations and low detection rates and were not analyzed further. Seventeen of 21 organochlorine pesticides [p,p′-DDT, p,p′-DDE, p,p′-DDD, o,p′-DDT, HCH (α , β, γ ), HCB, PCA, α -endosulfan, cis-HE, chlordane (cis-, trans-) oxychlordane, methoxychlor, OCS, and dieldrin] were measured in higher median concentrations in case milk than in control milk. Apart from trans-chlordane (p = 0

  18. The neurotensin receptor-1 pathway contributes to human ductal breast cancer progression.

    Science.gov (United States)

    Dupouy, Sandra; Viardot-Foucault, Véronique; Alifano, Marco; Souazé, Frédérique; Plu-Bureau, Geneviève; Chaouat, Marc; Lavaur, Anne; Hugol, Danielle; Gespach, Christian; Gompel, Anne; Forgez, Patricia

    2009-01-01

    The neurotensin (NTS) and its specific high affinity G protein coupled receptor, the NT1 receptor (NTSR1), are considered to be a good candidate for one of the factors implicated in neoplastic progression. In breast cancer cells, functionally expressed NT1 receptor coordinates a series of transforming functions including cellular migration and invasion. we investigated the expression of NTS and NTSR1 in normal human breast tissue and in invasive ductal breast carcinomas (IDCs) by immunohistochemistry and RT-PCR. NTS is expressed and up-regulated by estrogen in normal epithelial breast cells. NTS is also found expressed in the ductal and invasive components of IDCs. The high expression of NTSR1 is associated with the SBR grade, the size of the tumor, and the number of metastatic lymph nodes. Furthermore, the NTSR1 high expression is an independent factor of prognosis associated with the death of patients. these data support the activation of neurotensinergic deleterious pathways in breast cancer progression.

  19. Association between human breast milk and retinopathy of prematurity.

    Science.gov (United States)

    Fonseca, Luciana Teixeira; Senna, Denise C; Eckert, Gabriela Unchalo; Silveira, Rita de Cássia; Procianoy, Renato Soibelmann

    2018-04-01

    To evaluate the possible protective effect of breast milk against retinopathy of prematurity by comparing the amount of breast milk received by patients who developed retinopathy of prematurity and those who did not and to determine both the required minimum amount of breast milk and the time of life during which neonates need to receive breast milk for this effect to be significant. Cohort study of newborns with a birth weight of prematurity of any degree was 31% (100 of 323 patients) and that of severe retinopathy of prematurity was of 9% (29 of 323 patients). The median amounts of breast milk received daily by patients with and without retinopathy of prematurity were 4.9 mL/kg (interquartile range, 0.3-15.4) and 10.2 mL/kg (1.5-25.5), respectively. The amount of breast milk received in the first 6 weeks of life was inversely associated with the incidence of both retinopathy of prematurity of any degree and severe retinopathy of prematurity in the univariate analyses. However, the statistical significance was maintained only during the sixth week of life in a per-period multivariate analysis controlling for confounding factors. Small amounts of breast milk are inadequate to prevent retinopathy of prematurity in premature newborns at risk for the disease.

  20. Melatonin and breast cancer: Evidences from preclinical and human studies.

    Science.gov (United States)

    Kubatka, Peter; Zubor, Pavol; Busselberg, Dietrich; Kwon, Taeg Kyu; Adamek, Mariusz; Petrovic, Daniel; Opatrilova, Radka; Gazdikova, Katarina; Caprnda, Martin; Rodrigo, Luis; Danko, Jan; Kruzliak, Peter

    2018-02-01

    The breast cancer affects women with high mortality and morbidity worldwide. The risk is highest in the most developed world but also is markedly rising in the developing countries. It is well documented that melatonin has a significant anti-tumor activities demonstrated on various cancer types in a plethora of preclinical studies. In breast cancer, melatonin is capable to disrupt estrogen-dependent cell signaling, resulting in a reduction of estrogen-stimulated cells, moreover, it's obvious neuro-immunomodulatory effect in organism was described. Several prospective studies have demonstrated the inverse correlation between melatonin metabolites and the risk of breast cancer. This correlation was confirmed by observational studies that found lower melatonin levels in breast cancer patients. Moreover, clinical studies have showed that circadian disruption of melatonin synthesis, specifically night shift work, is linked to increased breast cancer risk. In this regard, proper light/dark exposure with more selective use of light at night along with oral supplementation of melatonin may have benefits for high-risk women. The results of current preclinical studies, the mechanism of action, and clinical efficacy of melatonin in breast cancer are reviewed in this paper. Melatonin alone or in combined administration seems to be appropriate drug for the treatment of early stages of breast cancer with documented low toxicity over a wide range of doses. These and other issues are also discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Leptin and Adiponectin Modulate the Self-renewal of Normal Human Breast Epithelial Stem Cells.

    Science.gov (United States)

    Esper, Raymond M; Dame, Michael; McClintock, Shannon; Holt, Peter R; Dannenberg, Andrew J; Wicha, Max S; Brenner, Dean E

    2015-12-01

    Multiple mechanisms are likely to account for the link between obesity and increased risk of postmenopausal breast cancer. Two adipokines, leptin and adiponectin, are of particular interest due to their opposing biologic functions and associations with breast cancer risk. In the current study, we investigated the effects of leptin and adiponectin on normal breast epithelial stem cells. Levels of leptin in human adipose explant-derived conditioned media positively correlated with the size of the normal breast stem cell pool. In contrast, an inverse relationship was found for adiponectin. Moreover, a strong linear relationship was observed between the leptin/adiponectin ratio in adipose conditioned media and breast stem cell self-renewal. Consistent with these findings, exogenous leptin stimulated whereas adiponectin suppressed breast stem cell self-renewal. In addition to local in-breast effects, circulating factors, including leptin and adiponectin, may contribute to the link between obesity and breast cancer. Increased levels of leptin and reduced amounts of adiponectin were found in serum from obese compared with age-matched lean postmenopausal women. Interestingly, serum from obese women increased stem cell self-renewal by 30% compared with only 7% for lean control serum. Taken together, these data suggest a plausible explanation for the obesity-driven increase in postmenopausal breast cancer risk. Leptin and adiponectin may function as both endocrine and paracrine/juxtacrine factors to modulate the size of the normal stem cell pool. Interventions that disrupt this axis and thereby normalize breast stem cell self-renewal could reduce the risk of breast cancer. ©2015 American Association for Cancer Research.

  2. Transjugular local thrombolysis with/without TIPS in patients with acute non-cirrhotic, non-malignant portal vein thrombosis.

    Science.gov (United States)

    Klinger, Christoph; Riecken, Bettina; Schmidt, Arthur; De Gottardi, Andrea; Meier, Benjamin; Bosch, Jaime; Caca, Karel

    2017-12-01

    Therapeutic anticoagulation is the standard treatment in patients with acute non-cirrhotic portal vein thrombosis (PVT). In critically ill patients, anticoagulation only may not suffice to achive rapid and stable recanalization. This study evaluates efficacy and safety of transjugular interventional therapy in acute non-cirrhotic PVT. This retrospective study includes 17 consecutive patients with acute noncirrhotic, non-malignant PVT. Main indication for interventional therapy was imminent intestinal infarction (n=10). Treatment consisted of a combination of transjugular thrombectomy, local fibrinolysis and - depending on thrombus resolution - transjugular intrahepatic portosystemic shunt. Recanalization was successful in 94.1%. One- and two-year secondary PV patency rates were 88.2%. Major complications (n=3) resolved spontaneously in all but one patient (heparin induced thrombocytopenia type 2 with intestinal infarction). Symptoms improved in all patients. However, segmental bowel resection had to be performed in two (11.8%). During a median follow-up of 28.6 months, no patient experienced portal hypertensive complications. Presence of JAK2 V617F mutation predicted both short-term and long-term technical success. Transjugular recanalization is safe and effective in patients with acute non-cirrhotic, non-malignant PVT. It should be considered especially in patients with imminent bowel infarction and low likelihood of recanalization following therapeutic anticoagulation. Patients with JAK2 mutation ought to be followed meticulously. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  3. Analysis of CD83 antigen expression in human breast fibroadenoma and adjacent tissue

    Directory of Open Access Journals (Sweden)

    Marcus Nascimento Borges

    Full Text Available CONTEXT AND OBJECTIVE: Dendritic cell maturation is considered essential for starting an immune response. The CD83 antigen is an important marker of dendritic cell maturation. The objectives here were to analyze CD83 antigen expression in human breast fibroadenoma and breast tissue adjacent to the lesion and to identify clinical factors that might influence this expression. DESIGN AND SETTING: This was a retrospective study at a public university hospital, in which 29 histopathological samples of breast fibroadenoma and adjacent breast tissue, from 28 women of reproductive age, were analyzed. METHODS: The immunohistochemistry method was used to analyze the cell expression of the antigen. The antigen expression in the cells was evaluated by means of random manual counting using an optical microscope. RESULTS: Positive expression of the CD83 antigen in the epithelial cells of the fibroadenoma (365.52; standard deviation ± 133.13 in relation to the adjacent breast tissue cells (189.59; standard deviation ± 140.75 was statistically larger (P < 0.001. Several clinical features were analyzed, but only parity was shown to influence CD83 antigen expression in the adjacent breast tissue, such that positive expression was more evident in nulliparous women (P = 0.042. CONCLUSIONS: The expression of the CD83 antigen in the fibroadenoma was positive and greater than in the adjacent breast tissue. Positive expression of the antigen in the adjacent breast tissue was influenced by parity, and was significantly more evident in nulliparous women.

  4. A novel imidazopyridine analogue as a phosphatidylinositol 3-kinase inhibitor against human breast cancer.

    Science.gov (United States)

    Lee, Hyunseung; Li, Guang-Yong; Jeong, Yujeong; Jung, Kyung Hee; Lee, Ju-Hee; Ham, Kyungrok; Hong, Sungwoo; Hong, Soon-Sun

    2012-05-01

    Potentiation of anti-breast cancer activity of an imidazopyridine-based PI3Kα inhibitor, HS-104, was investigated in human breast cancer cells. HS-104 shows strong inhibitory activity against recombinant PI3Kα isoform and the PI3K signaling pathway, resulting in anti-proliferative activity in breast cancer cells. It also induced cell cycle arrest at the G(2)/M phase as well as apoptosis. Furthermore, oral administration of HS-104 significantly inhibited the growth of tumor in SkBr3 mouse xenograft models. Therefore, HS-104 could be considered as a potential candidate for the treatment of human breast cancer. Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

  5. Three-dimensional in vivo fluorescence diffuse optical tomography of breast cancer in humans

    Science.gov (United States)

    Corlu, Alper; Choe, Regine; Durduran, Turgut; Rosen, Mark A.; Schweiger, Martin; Arridge, Simon R.; Schnall, Mitchell D.; Yodh, Arjun G.

    2007-05-01

    We present three-dimensional (3D) in vivo images of human breast cancer based on fluorescence diffuse optical tomography (FDOT). To our knowledge, this work represents the first reported 3D fluorescence tomography of human breast cancer in vivo. In our protocol, the fluorophore Indocyanine Green (ICG) is injected intravenously. Fluorescence excitation and detection are accomplished in the soft-compression, parallel-plane, transmission geometry using laser sources at 786 nm and spectrally filtered CCD detection. Phantom and in vivo studies confirm the signals are due to ICG fluorescence, rather than tissue autofluorescence and excitation light leakage. Fluorescence images of breast tumors were in good agreement with those of MRI, and with DOT based on endogenous contrast. Tumorto- normal tissue contrast based on ICG fluorescence was two-to-four-fold higher than contrast based on hemoglobin and scattering parameters. In total the measurements demonstrate that FDOT of breast cancer is feasible and promising.

  6. Stability of Cortisol and Cortisone in Human Breast Milk During Holder Pasteurization.

    Science.gov (United States)

    van der Voorn, Bibian; de Waard, Marita; Dijkstra, Lisette R; Heijboer, Annemieke C; Rotteveel, Joost; van Goudoever, Johannes B; Finken, Martijn J J

    2017-12-01

    Human donor milk is the feeding of choice for preterm infants, when own mother's milk is not available. Holder pasteurization is necessary to secure the safety of donor milk, although it can affect milk quality by reduction of nutritional and bioactive components. Recently, research has focused on the potential role of breast milk glucocorticoids for infant development. At this moment, it is unknown whether pasteurization affects milk glucocorticoid levels. Therefore, we assessed whether Holder pasteurization, the most frequently used method nowadays, reduces breast milk cortisol and cortisone levels, using breast milk samples from 30 women who delivered at term. We found tight correlations between pre- and postpasteurization levels of cortisol (R = 0.99) and cortisone (R = 0.98), and good agreement in Passing and Bablok regression analysis. In conclusion, cortisol and cortisone in human term breast milk are not significantly affected by Holder pasteurization.

  7. Characterization of human breast cancer tissues by infrared imaging.

    Science.gov (United States)

    Verdonck, M; Denayer, A; Delvaux, B; Garaud, S; De Wind, R; Desmedt, C; Sotiriou, C; Willard-Gallo, K; Goormaghtigh, E

    2016-01-21

    Fourier Transform InfraRed (FTIR) spectroscopy coupled to microscopy (IR imaging) has shown unique advantages in detecting morphological and molecular pathologic alterations in biological tissues. The aim of this study was to evaluate the potential of IR imaging as a diagnostic tool to identify characteristics of breast epithelial cells and the stroma. In this study a total of 19 breast tissue samples were obtained from 13 patients. For 6 of the patients, we also obtained Non-Adjacent Non-Tumor tissue samples. Infrared images were recorded on the main cell/tissue types identified in all breast tissue samples. Unsupervised Principal Component Analyses and supervised Partial Least Square Discriminant Analyses (PLS-DA) were used to discriminate spectra. Leave-one-out cross-validation was used to evaluate the performance of PLS-DA models. Our results show that IR imaging coupled with PLS-DA can efficiently identify the main cell types present in FFPE breast tissue sections, i.e. epithelial cells, lymphocytes, connective tissue, vascular tissue and erythrocytes. A second PLS-DA model could distinguish normal and tumor breast epithelial cells in the breast tissue sections. A patient-specific model reached particularly high sensitivity, specificity and MCC rates. Finally, we showed that the stroma located close or at distance from the tumor exhibits distinct spectral characteristics. In conclusion FTIR imaging combined with computational algorithms could be an accurate, rapid and objective tool to identify/quantify breast epithelial cells and differentiate tumor from normal breast tissue as well as normal from tumor-associated stroma, paving the way to the establishment of a potential complementary tool to ensure safe tumor margins.

  8. Recurrent Breast Abscesses due to Corynebacterium kroppenstedtii, a Human Pathogen Uncommon in Caucasian Women

    Directory of Open Access Journals (Sweden)

    Anne Le Flèche-Matéos

    2012-01-01

    Full Text Available Background. Corynebacterium kroppenstedtii (Ck was first described in 1998 from human sputum. Contrary to what is observed in ethnic groups such as Maori, Ck is rarely isolated from breast abscesses and granulomatous mastitis in Caucasian women. Case Presentation. We herein report a case of recurrent breast abscesses in a 46-year-old Caucasian woman. Conclusion. In the case of recurrent breast abscesses, even in Caucasian women, the possible involvement of Ck should be investigated. The current lack of such investigations, probably due to the difficulty to detect Ck, may cause the underestimation of such an aetiology.

  9. Immunomodulatory constituents of human breast milk and immunity from bronchiolitis.

    Science.gov (United States)

    Li, Chunyu; Liu, Yanbo; Jiang, Yanfang; Xu, Naijun; Lei, Jie

    2017-01-14

    The mother's immune status can be achieved by genetic and breastfeeding impact descendants of the immune system. The study aimed to determine whether a mother's immune status and breastfeeding practices were related to development of bronchiolitis in her infant. The frequency of T, B and natural kill (NK) cells in patients' blood and their mothers' breast milk was determined using flow cytometry. The concentrations of serum and breast milk IgG and IgD in individual patients and healthy control were determined by enzyme-linked immunosorbent assay (ELISA). The relationships between immunocytes, immunoglobulin and respiratory score (RS) were analyzed by Spearman's rank correlation test. The mothers of bronchiolitis patients had lower IgG concentrations in their breast milk when compared to the mothers of healthy children. There was no significant difference in the frequency of T cells, B cells, and NK cells in samples of breast milk. However, significant decreases of CD3+, CD8+ T cells, as well as significant increases of CD4+ T cells and CD19+ B cells were found in the serum of bronchiolitis infants. There were positive correlation relationships between RS and CD3+, CD4+ T cells, IgG and IgD concentrations. Our data suggested that the mothers of bronchiolitis patients had lower IgG concentration in their breast milk. The breast milk IgG might be absorbed by the breastfeeding infants, which could play important role in resistance of bronchiolitis.

  10. Human breast cancer histoid: an in vitro 3-dimensional co-culture model that mimics breast cancer tissue.

    Science.gov (United States)

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

    2011-12-01

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

  11. Inactivation of Zika virus in human breast milk by prolonged storage or pasteurization.

    Science.gov (United States)

    Pfaender, Stephanie; Vielle, Nathalie J; Ebert, Nadine; Steinmann, Eike; Alves, Marco P; Thiel, Volker

    2017-01-15

    Zika virus infection during pregnancy poses a serious risk for pregnant women as it can cause severe birth defects. Even though the virus is mainly transmitted via mosquitos, human-to-human transmission has been described. Infectious viral particles have been detected in breast milk of infected women which raised concerns regarding the safety of breastfeeding in areas of Zika virus transmission or in case of a suspected or confirmed Zika virus infection. In this study, we show that Zika virus is effectively inactivated in human breast milk after prolonged storage or upon pasteurization of milk. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Inhibition of Notch1 increases paclitaxel sensitivity to human breast cancer

    Institute of Scientific and Technical Information of China (English)

    Zhao Li; Ma Yongjie; Gu Feng; Fu Li

    2014-01-01

    Background Paclitaxel (PAC) is the first-line chemotherapy drug for most breast cancer patients,but clinical studies showed that some breast cancer patients were insensitive to PAC,which led to chemotherapy failure.It was reported that Notch1 signaling participated in drug resistance of breast cancer.Here,we show whether Notch1 expression is related to PAC sensitivity of breast cancer.Methods We employed Notch1 siRNA and Notch1 inhibitor,N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester (DAPT),to down regulate Notch1 expression in human breast cancer cells MDA-MB-231,and detected the inhibition effect by Western blotting and reverse trans cription-polymerase chain reaction,respectively.After 24 hours exposure to different concentration of PAC (0,1,5,10,15,20,and 25 μg/ml),the viability of the control group and experimental group cells was tested by MTT.We also examined the expression of Notch1 in PAC sensitive and nonsensitive breast cancer patients,respectively by immunohistochemistry (IHC).The PAC sensitivity of breast cancer patients were identified by collagen gel droplet embedded culture-drug sensitivity test (CD-DST).Results Down regulation of Notch1 expression by Notch1siRNA interference or Notch1 inhibitor increased the PAC sensitivity in MDA-MB-231 cells (P <0.05).Also,the expression of Notch1 in PAC sensitive patients was much lower than that of PAC non-sensitive patients (P <0.01).Conclusion Notch1 expression has an effect on PAC sensitivity in breast cancer patients,and the inhibition of Notch1 increases paclitaxel sensitivity to human breast cancer.

  13. 31P MRSI and 1H MRS at 7 T: initial results in human breast cancer.

    Science.gov (United States)

    Klomp, Dennis W J; van de Bank, Bart L; Raaijmakers, Alexander; Korteweg, Mies A; Possanzini, Cecilia; Boer, Vincent O; van de Berg, Cornelius A T; van de Bosch, Maurice A A J; Luijten, Peter R

    2011-12-01

    This study demonstrates the feasibility of the noninvasive determination of important biomarkers of human (breast) tumor metabolism using high-field (7-T) MRI and MRS. (31) P MRSI at this field strength was used to provide a direct method for the in vivo detection and quantification of endogenous biomarkers. These encompass phospholipid metabolism, phosphate energy metabolism and intracellular pH. A double-tuned, dual-element transceiver was designed with focused radiofrequency fields for unilateral breast imaging and spectroscopy tuned for optimized sensitivity at 7 T. T(1) -weighted three-dimensional MRI and (1) H MRS were applied for the localization and quantification of total choline compounds. (31) P MRSI was obtained within 20 min per subject and mapped in three dimensions over the breast with pixel volumes of 10 mL. The feasibility of monitoring in vivo metabolism was demonstrated in two patients with breast cancer during neoadjuvant chemotherapy, validated by ex vivo high-resolution magic angle spinning NMR and compared with data from an age-matched healthy volunteer. Concentrations of total choline down to 0.4 mM could be detected in the human breast in vivo. Levels of adenosine and other nucleoside triphosphates, inorganic phosphate, phosphocholine, phosphoethanolamine and their glycerol diesters detected in glandular tissue, as well as in tumor, were mapped over the entire breast. Altered levels of these compounds were observed in patients compared with an age-matched healthy volunteer; modulation of these levels occurred in breast tumors during neoadjuvant chemotherapy. To our knowledge, this is the first comprehensive MRI and MRS study in patients with breast cancer, which reveals detailed information on the morphology and phospholipid metabolism from volumes as small as 10 mL. This endogenous metabolic information may provide a new method for the noninvasive assessment of prognostic and predictive biomarkers in breast cancer treatment. Copyright

  14. Cytotoxicity Study of Cyclopentapeptide Analogues of Marine Natural Product Galaxamide towards Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Jignesh Lunagariya

    2017-01-01

    Full Text Available Herein, we report the cytotoxicity of cyclopentapeptide analogues of marine natural product galaxamide towards breast carcinoma cells and the underlying mechanisms. We examined the effect of the novel galaxamide analogues on cancer cell proliferation by MTT assay and also further examined the most active compound for morphological changes using Hoechst33342 staining technique, induction of apoptosis, cell cycle phases, mitochondrial membrane potential (MMP, and reactive oxygen species (ROS generation using flow cytometry in human breast cancer MCF-7 cells in vitro. Galaxamide and its analogues effectively induced toxicity in human hepatocellular carcinoma HepG2, human breast carcinoma MCF-7, human epitheloid cervix carcinoma HeLa, and human breast carcinoma MB-MDA-231 cell lines. Amongst them, compound 3 exhibited excellent toxicity towards MCF-7 cells. This galaxamide analogue significantly induced apoptosis in a dose-dependent manner in MCF-7 cells involves cell cycle arrest in the G1 phase, a reduction of MMP, and a marked increase in generation of ROS. Particularly, compound 3 of galaxamide analogues might be a potential candidate for the treatment of breast cancer.

  15. Population of 224 realistic human subject-based computational breast phantoms

    Energy Technology Data Exchange (ETDEWEB)

    Erickson, David W. [Carl E. Ravin Advanced Imaging Laboratories, Duke University Medical Center, Durham, North Carolina 27705 and Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States); Wells, Jered R., E-mail: jered.wells@duke.edu [Clinical Imaging Physics Group and Carl E. Ravin Advanced Imaging Laboratories, Duke University Medical Center, Durham, North Carolina 27705 and Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States); Sturgeon, Gregory M. [Carl E. Ravin Advanced Imaging Laboratories, Duke University Medical Center, Durham, North Carolina 27705 (United States); Samei, Ehsan [Department of Radiology and Carl E. Ravin Advanced Imaging Laboratories, Duke University Medical Center, Durham, North Carolina 27705 and Departments of Physics, Electrical and Computer Engineering, and Biomedical Engineering, and Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States); Dobbins, James T. [Department of Radiology and Carl E. Ravin Advanced Imaging Laboratories, Duke University Medical Center, Durham, North Carolina 27705 and Departments of Physics and Biomedical Engineering and Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States); Segars, W. Paul [Department of Radiology and Carl E. Ravin Advanced Imaging Laboratories, Duke University Medical Center, Durham, North Carolina 27705 and Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States); Lo, Joseph Y. [Department of Radiology and Carl E. Ravin Advanced Imaging Laboratories, Duke University Medical Center, Durham, North Carolina 27705 and Departments of Electrical and Computer Engineering and Biomedical Engineering and Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States)

    2016-01-15

    Purpose: To create a database of highly realistic and anatomically variable 3D virtual breast phantoms based on dedicated breast computed tomography (bCT) data. Methods: A tissue classification and segmentation algorithm was used to create realistic and detailed 3D computational breast phantoms based on 230 + dedicated bCT datasets from normal human subjects. The breast volume was identified using a coarse three-class fuzzy C-means segmentation algorithm which accounted for and removed motion blur at the breast periphery. Noise in the bCT data was reduced through application of a postreconstruction 3D bilateral filter. A 3D adipose nonuniformity (bias field) correction was then applied followed by glandular segmentation using a 3D bias-corrected fuzzy C-means algorithm. Multiple tissue classes were defined including skin, adipose, and several fractional glandular densities. Following segmentation, a skin mask was produced which preserved the interdigitated skin, adipose, and glandular boundaries of the skin interior. Finally, surface modeling was used to produce digital phantoms with methods complementary to the XCAT suite of digital human phantoms. Results: After rejecting some datasets due to artifacts, 224 virtual breast phantoms were created which emulate the complex breast parenchyma of actual human subjects. The volume breast density (with skin) ranged from 5.5% to 66.3% with a mean value of 25.3% ± 13.2%. Breast volumes ranged from 25.0 to 2099.6 ml with a mean value of 716.3 ± 386.5 ml. Three breast phantoms were selected for imaging with digital compression (using finite element modeling) and simple ray-tracing, and the results show promise in their potential to produce realistic simulated mammograms. Conclusions: This work provides a new population of 224 breast phantoms based on in vivo bCT data for imaging research. Compared to previous studies based on only a few prototype cases, this dataset provides a rich source of new cases spanning a wide range

  16. Differential expression of follistatin and FLRG in human breast proliferative disorders

    Directory of Open Access Journals (Sweden)

    Amaral Vania F

    2009-09-01

    Full Text Available Abstract Background Activins are growth factors acting on cell growth and differentiation. Activins are expressed in high grade breast tumors and they display an antiproliferative effect inducing G0/G1 cell cycle arrest in breast cancer cell lines. Follistatin and follistatin- related gene (FLRG bind and neutralize activins. In order to establish if these activin binding proteins are involved in breast tumor progression, the present study evaluated follistatin and FLRG pattern of mRNA and protein expression in normal human breast tissue and in different breast proliferative diseases. Methods Paraffin embedded specimens of normal breast (NB - n = 8; florid hyperplasia without atypia (FH - n = 17; fibroadenoma (FIB - n = 17; ductal carcinoma in situ (DCIS - n = 10 and infiltrating ductal carcinoma (IDC - n = 15 were processed for follistatin and FLRG immunohistochemistry and in situ hybridization. The area and intensity of chromogen epithelial and stromal staining were analyzed semi-quantitatively. Results Follistatin and FLRG were expressed both in normal tissue and in all the breast diseases investigated. Follistatin staining was detected in the epithelial cytoplasm and nucleus in normal, benign and malignant breast tissue, with a stronger staining intensity in the peri-alveolar stromal cells of FIB at both mRNA and protein levels. Conversely, FLRG area and intensity of mRNA and protein staining were higher both in the cytoplasm and in the nucleus of IDC epithelial cells when compared to NB, while no significant changes in the stromal intensity were observed in all the proliferative diseases analyzed. Conclusion The present findings suggest a role for follistatin in breast benign disease, particularly in FIB, where its expression was increased in stromal cells. The up regulation of FLRG in IDC suggests a role for this protein in the progression of breast malignancy. As activin displays an anti-proliferative effect in human mammary cells, the

  17. Overexpression of SERBP1 (Plasminogen activator inhibitor 1 RNA binding protein) in human breast cancer is correlated with favourable prognosis

    International Nuclear Information System (INIS)

    Serce, Nuran Bektas; Knuechel, Ruth; Beckmann, Matthias W; Fasching, Peter A; Dahl, Edgar; Boesl, Andreas; Klaman, Irina; Serényi, Sonja von; Noetzel, Erik; Press, Michael F; Dimmler, Arno; Hartmann, Arndt; Sehouli, Jalid

    2012-01-01

    Plasminogen activator inhibitor 1 (PAI-1) overexpression is an important prognostic and predictive biomarker in human breast cancer. SERBP1, a protein that is supposed to regulate the stability of PAI-1 mRNA, may play a role in gynaecological cancers as well, since upregulation of SERBP1 was described in ovarian cancer recently. This is the first study to present a systematic characterisation of SERBP1 expression in human breast cancer and normal breast tissue at both the mRNA and the protein level. Using semiquantitative realtime PCR we analysed SERBP1 expression in different normal human tissues (n = 25), and in matched pairs of normal (n = 7) and cancerous breast tissues (n = 7). SERBP1 protein expression was analysed in two independent cohorts on tissue microarrays (TMAs), an initial evaluation set, consisting of 193 breast carcinomas and 48 normal breast tissues, and a second large validation set, consisting of 605 breast carcinomas. In addition, a collection of benign (n = 2) and malignant (n = 6) mammary cell lines as well as breast carcinoma lysates (n = 16) were investigated for SERBP1 expression by Western blot analysis. Furthermore, applying non-radioisotopic in situ hybridisation a subset of normal (n = 10) and cancerous (n = 10) breast tissue specimens from the initial TMA were analysed for SERBP1 mRNA expression. SERBP1 is not differentially expressed in breast carcinoma compared to normal breast tissue, both at the RNA and protein level. However, recurrence-free survival analysis showed a significant correlation (P = 0.008) between abundant SERBP1 expression in breast carcinoma and favourable prognosis. Interestingly, overall survival analysis also displayed a tendency (P = 0.09) towards favourable prognosis when SERBP1 was overexpressed in breast cancer. The RNA-binding protein SERBP1 is abundantly expressed in human breast cancer and may represent a novel breast tumour marker with prognostic significance. Its potential involvement in the

  18. The Role of Osteopontin in the Malignancy of Human Breast Carcinoma

    Science.gov (United States)

    1999-07-01

    1997; Yebra et al., 1996). 1990). Probes for human proteinase and uPAR genes The finding that human breast epithelial cells up- included: MMP-9 (92...680 -Senger DR and Perruzzi CA. (1996). Biochim. Biaphys. 69D.Adta., 1314, 13-24. Yebra M, Parry GCN, Str6mblad S, Mackman N,Shanmugamn V

  19. The sodium iodide symporter (NIS) and potential regulators in normal, benign and malignant human breast tissue.

    LENUS (Irish Health Repository)

    Ryan, James

    2011-01-01

    The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro.

  20. Nutrient-enriched formula milk versus human breast milk for preterm infants following hospital discharge.

    Science.gov (United States)

    Henderson, G; Fahey, T; McGuire, W

    2007-10-17

    Preterm infants are often growth-restricted at hospital discharge. Feeding infants after hospital discharge with nutrient-enriched formula milk instead of human breast milk might facilitate "catch-up" growth and improve development. To determine the effect of feeding nutrient-enriched formula compared with human breast milk on growth and development of preterm infants following hospital discharge. The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2007), MEDLINE (1966 - May 2007), EMBASE (1980 - May 2007), CINAHL (1982 - May 2007), conference proceedings, and previous reviews. Randomised or quasi-randomised controlled trials that compared feeding preterm infants following hospital discharge with nutrient-enriched formula compared with human breast milk. The standard methods of the Cochrane Neonatal Review Group were used, with separate evaluation of trial quality and data extraction by two review authors. No eligible trials were identified. There are no data from randomised controlled trials to determine whether feeding preterm infants following hospital discharge with nutrient-enriched formula milk versus human breast milk affects growth and development. Mothers who wish to breast feed, and their health care advisors, would require very clear evidence that feeding with a nutrient-enriched formula milk had major advantages for their infants before electing not to feed (or to reduce feeding) with maternal breast milk. If evidence from trials that compared feeding preterm infants following hospital discharge with nutrient-enriched versus standard formula milk demonstrated an effect on growth or development, then this might strengthen the case for undertaking trials of nutrient-enriched formula milk versus human breast milk.

  1. The assay of estrogen receptors in three components of human breast cancer tissue

    International Nuclear Information System (INIS)

    Lu Hanping; Gui Zhining

    1992-01-01

    The binding capacities of estrogen receptors in nuclear matrix, nuclei and cytosol of human breast cancer tissue (EmR, EnR, EcR) were estimated with radioligand binding assay of receptors. The average B max values of these components in 21 breast cancer specimens are 417.54 ± 170.95, 147.75 ± 98.32, 7.34 ± 5.33 fmol/mg protein, and those in 10 normal breast tissue specimens are 42.33 ± 8.49, 25.05 ± 7.81, 5.91 ± 2.28 fmol/mg protein. Comparing the cancer and normal breast tissues, there is significant difference in B max values of EmR and EnR (P max values of EcR (P > 0.10). The EmR/EnR value of 21 breast cancer tissue is 0.65 ± 0.10, and that of 10 normal breast tissue is 0.42 ± 0.04. There is statistical difference between the cancer and normal. 10 of 13 (77%) patients, who are EcR-positive, have higher EmR/EnR values (≥0.50). The results suggest that estrogen receptors are mainly located at the nuclear matrix, ER levels in nucleus, especially in nuclear matrix of breast cancer tissue are valuable parameters and may be useful for predicting whether the patient will be responsible to endocrine therapy

  2. Analysis of CD83 antigen expression in human breast fibroadenoma and adjacent tissue.

    Science.gov (United States)

    Borges, Marcus Nascimento; Facina, Gil; Silva, Ismael Dale Cotrin Guerreiro; Waitzberg, Angela Flávia Logullo; Nazario, Afonso Celso Pinto

    2011-12-01

    Dendritic cell maturation is considered essential for starting an immune response. The CD83 antigen is an important marker of dendritic cell maturation. The objectives here were to analyze CD83 antigen expression in human breast fibroadenoma and breast tissue adjacent to the lesion and to identify clinical factors that might influence this expression. This was a retrospective study at a public university hospital, in which 29 histopathological samples of breast fibroadenoma and adjacent breast tissue, from 28 women of reproductive age, were analyzed. The immunohistochemistry method was used to analyze the cell expression of the antigen. The antigen expression in the cells was evaluated by means of random manual counting using an optical microscope. Positive expression of the CD83 antigen in the epithelial cells of the fibroadenoma (365.52; standard deviation ± 133.13) in relation to the adjacent breast tissue cells (189.59; standard deviation ± 140.75) was statistically larger (P fibroadenoma was positive and greater than in the adjacent breast tissue. Positive expression of the antigen in the adjacent breast tissue was influenced by parity, and was significantly more evident in nulliparous women.

  3. Breast

    International Nuclear Information System (INIS)

    Ribeiro, G.G.

    1985-01-01

    The treatment of malignant disease of the breast arouses more controversy and emotion than that of any other form of malignant disease. Many clinical trials have been carried out and others are still in progress. In addition, research work continues in regard to other aspects of the disease, such as epidemiology, population screening, and endocrine factors; yet little is really known about the true biological nature of carcinoma of the breast. A vast amount of literature has accumulated on the treatment of ''operable'' carcinoma of the breast, but it is not proposed to discuss here the merits or demerits of the various suggested treatments. Instead this chapter will be confined to the practical management of carcinoma of the breast as seen from the point of view of radiotherapist. For this reason greater attention will be paid to the radiotherapy techniques as practised at the Christie Hospital

  4. Degradation of endothelial basement membrane by human breast cancer cell lines

    International Nuclear Information System (INIS)

    Yee, C.; Shiu, R.P.

    1986-01-01

    During metastasis, it is believed that tumor cells destroy the basement membrane (BM) of blood vessels in order to disseminate through the circulatory system. By radioactively labeling the extracellular matrix produced by primary endothelial cells in vitro, the ability of human breast cancer cells to degrade BM components was studied. We found that T-47D, a human breast cancer line, was able to degrade significant amounts of [35S]methionine-labeled and [3H]proline-labeled BM, but not 35SO4-labeled BM. Six other tumor cell lines of human breast origin were assayed in the same manner and were found to degrade BM to varying degrees. Several non-tumor cell lines tested showed relatively little degrading activity. The use of serum-free medium greatly enhanced degradation of the BM by tumor cells, suggesting a role for naturally occurring enzyme inhibitors in the serum. Direct cell contact with the BM was required for BM degradation, suggesting that the active enzymes are cell associated. The addition of hormones implicated in the etiology of breast cancer did not significantly alter the ability of T-47D cells to degrade the BM. The use of this assay affords future studies on the mechanism of invasion and metastasis of human breast cancer

  5. Neuroligin 4X overexpression in human breast cancer is associated with poor relapse-free survival.

    Directory of Open Access Journals (Sweden)

    Henry J Henderson

    Full Text Available The molecular mechanisms involved in breast cancer progression and metastasis still remain unclear to date. It is a heterogeneous disease featuring several different phenotypes with consistently different biological characteristics. Neuroligins are neural cell adhesion molecules that have been implicated in heterotopic cell adhesion. In humans, alterations in neuroligin genes are implicated in autism and other cognitive diseases. Until recently, neuroligins have been shown to be abundantly expressed in blood vessels and also play a role implicated in the growth of glioma cells. Here we report increased expression of neuroligin 4X (NLGN4X in breast cancer. We found NLGN4X was abundantly expressed in breast cancer tissues. NLGN4X expression data for all breast cancer cell lines in the Cancer Cell Line Encyclopedia (CCLE was analyzed. Correlation between NLGN4X levels and clinicopathologic parameters were analyzed within Oncomine datasets. Evaluation of these bioinfomatic datasets results revealed that NLGN4X expression was higher in triple negative breast cancer cells, particularly the basal subtype and tissues versus non-triple-negative sets. Its level was also observed to be higher in metastatic tissues. RT-PCR, flow cytometry and immunofluorescence study of MDA-MB-231 and MCF-7 breast cancer cells validated that NLGN4X was increased in MDA-MB-231. Knockdown of NLGN4X expression by siRNA decreased cell proliferation and migration significantly in MDA-MB-231 breast cancer cells. NLGN4X knockdown in MDA-MB-231 cells resulted in induction of apoptosis as determined by annexin staining, elevated caspase 3/7 and cleaved PARP by flow cytometry. High NLGN4X expression highly correlated with decrease in relapse free-survival in TNBC. NLGN4X might represent novel biomarkers and therapeutic targets for breast cancer. Inhibition of NLGN4X may be a new target for the prevention and treatment of breast cancer.

  6. Investigation on main source of dioxin analogues in human breast milk (second report)

    Energy Technology Data Exchange (ETDEWEB)

    Miyata, H.; Nakao, T.; Aozasa, O.; Ohta, S. [Setsunan Univ., Hirakata (Japan); Iwamatsu, T. [Teijin Eco Science, Co. Ltd., Matsuyama (Japan); Fujimine, Y. [Otsuka Pharmaceutical Co. Ltd., Tokushima (Japan); Fukui, S. [Fukui Lactation Consultation, Amagasaki (Japan)

    2004-09-15

    In many countries, the breast milk sample has been used as a suitable indicator in order to examine human exposure level to Dioxins. In general, the breast milk level is considered to be reflecting to their accumulation level in the body. In addition, it is considered that ca. 60% of the accumulation amount of Dioxins is excreted to the baby through breast milk by nursing for a year. However, are these things true? In 1989, Frust et al. reported a time course of concentrations of Dioxins (abbreviated as Dioxins) in breast milk of one German during a period of 1 - 60 weeks after delivery. In the case of PCDFs, the level of 10 - 13 weeks after delivery was remarkably higher than that of 5 weeks. In addition, the PCBs level on the 10 to 13 weeks was also higher in comparison with on the 1 week. Thus, their pollution levels did not always decrease with a passing of time after childbirth. This suggests that all Dioxins in breast milk might be not derived from their storage in the body. Therefore, in 2001, we investigated the time alteration on the pollution level of Dioxins in breast milk from nine mothers and on their infants' daily intake of Dioxins by nursing. Consequently, it was revealed that the average daily intake of PCDD/DFs (PCDDs + PCDFs) was roughly constant during a period of 5 to 180 days after delivery. If all PCDD/DFs in breast milk are derived from only their body storage, the pollution level in milk must decrease in a linear course during a period of 5 to 180 days after delivery. However, thus linear decrease of pollution level was not observed in all tested mothers. These results indicated that PCDD/DFs in milk might be also delivered from other sources except for their storage in the body. Therefore, in this study, we tried to investigate the source of Dioxins in human breast milk.

  7. Molecular profiles of progesterone receptor loss in human breast tumors

    NARCIS (Netherlands)

    Creighton, Chad J.; Kent Osborne, C.; van de Vijver, Marc J.; Foekens, John A.; Klijn, Jan G.; Horlings, Hugo M.; Nuyten, Dimitry; Wang, Yixin; Zhang, Yi; Chamness, Gary C.; Hilsenbeck, Susan G.; Lee, Adrian V.; Schiff, Rachel

    2009-01-01

    Background Patient prognosis and response to endocrine therapy in breast cancer correlate with protein expression of both estrogen receptor (ER) and progesterone receptor (PR), with poorer outcome in patients with ER+/PR- compared to ER+/PR+ tumors. Methods To better understand the underlying

  8. Hard X-ray Microscopic Imaging Of Human Breast Tissues

    Science.gov (United States)

    Park, Sung H.; Kim, Hong T.; Kim, Jong K.; Jheon, Sang H.; Youn, Hwa S.

    2007-01-01

    X-ray microscopy with synchrotron radiation will be a useful tool for innovation of x-ray imaging in clinical and laboratory settings. It helps us observe detailed internal structure of material samples non-invasively in air. And, it also has the potential to solve some tough problems of conventional breast imaging if it could evaluate various conditions of breast tissue effectively. A new hard x-ray microscope with a spatial resolution better than 100 nm was installed at Pohang Light Source, a third generation synchrotron radiation facility in Pohang, Korea. The x-ray energy was set at 6.95 keV, and the x-ray beam was monochromatized by W/B4C monochromator. Condenser and objective zone plates were used as x-ray lenses. Zernike phase plate next to condenser zone plate was introduced for improved contrast imaging. The image of a sample was magnified 30 times by objective zone plate and 20 times by microscope objective, respectively. After additional 10 times digital magnification, the total magnifying power was up to 6000 times in the end. Phase contrast synchrotron images of 10-μm-thick female breast tissue of the normal, fibroadenoma, fibrocystic change and carcinoma cases were obtained. By phase contrast imaging, hard x-rays enable us to observe many structures of breast tissue without sample preparations such as staining or fixation.

  9. Hard X-ray Microscopic Imaging Of Human Breast Tissues

    International Nuclear Information System (INIS)

    Park, Sung H.; Kim, Hong T.; Kim, Jong K.; Jheon, Sang H.; Youn, Hwa S.

    2007-01-01

    X-ray microscopy with synchrotron radiation will be a useful tool for innovation of x-ray imaging in clinical and laboratory settings. It helps us observe detailed internal structure of material samples non-invasively in air. And, it also has the potential to solve some tough problems of conventional breast imaging if it could evaluate various conditions of breast tissue effectively. A new hard x-ray microscope with a spatial resolution better than 100 nm was installed at Pohang Light Source, a third generation synchrotron radiation facility in Pohang, Korea. The x-ray energy was set at 6.95 keV, and the x-ray beam was monochromatized by W/B4C monochromator. Condenser and objective zone plates were used as x-ray lenses. Zernike phase plate next to condenser zone plate was introduced for improved contrast imaging. The image of a sample was magnified 30 times by objective zone plate and 20 times by microscope objective, respectively. After additional 10 times digital magnification, the total magnifying power was up to 6000 times in the end. Phase contrast synchrotron images of 10-μm-thick female breast tissue of the normal, fibroadenoma, fibrocystic change and carcinoma cases were obtained. By phase contrast imaging, hard x-rays enable us to observe many structures of breast tissue without sample preparations such as staining or fixation

  10. Evaluation of human epidermal growth factor receptor 2 (HER2) single nucleotide polymorphisms (SNPs) in normal and breast tumor tissues and their link with breast cancer prognostic factors.

    Science.gov (United States)

    Furrer, Daniela; Lemieux, Julie; Côté, Marc-André; Provencher, Louise; Laflamme, Christian; Barabé, Frédéric; Jacob, Simon; Michaud, Annick; Diorio, Caroline

    2016-12-01

    Amplification of the human epidermal growth factor receptor 2 (HER2) gene is associated with worse prognosis and decreased overall survival in breast cancer patients. The HER2 gene contains several polymorphisms; two of the best-characterized HER2 polymorphisms are Ile655Val and Ala1170Pro. The aim of this study was to evaluate the association between these two HER2 polymorphisms in normal breast and breast cancer tissues and known breast cancer prognostic factors in a retrospective cohort study of 73 women with non-metastatic HER2-positive breast cancer. HER2 polymorphisms were assessed in breast cancer tissue and normal breast tissue using TaqMan assay. Ala1170Pro polymorphism in normal breast tissue was associated with age at diagnosis (p = 0.007), tumor size (p = 0.004) and lymphovascular invasion (p = 0.06). Similar significant associations in cancer tissues were observed. No association between the Ile655Val polymorphism and prognostic factors were observed. However, we found significant differences in the distribution of Ile655Val (p = 0.03) and Ala1170Pro (p = 0.01) genotypes between normal breast and breast tumor tissues. This study demonstrates that only the Ala1170Pro polymorphism is associated with prognostic factors in HER2-positive breast cancer patients. Moreover, our results suggest that both HER2 polymorphisms could play a significant role in carcinogenesis in non-metastatic HER2-positive breast cancer women. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Biological responses of progestogen metabolites in normal and cancerous human breast.

    Science.gov (United States)

    Pasqualini, Jorge R; Chetrite, Gérard S

    2010-12-01

    At present, more than 200 progestogen molecules are available, but their biological response is a function of various factors: affinity to progesterone or other receptors, their structure, the target tissues considered, biological response, experimental conditions, dose, method of administration and metabolic transformations. Metabolic transformation is of huge importance because in various biological processes the metabolic product(s) not only control the activity of the maternal hormone but also have an important activity of its own. In this regard, it was observed that the 20-dihydro derivative of the progestogen dydrogesterone (Duphaston®) is significantly more active than the parent compound in inhibiting sulfatase and 17β-hydroxysteroid dehydrogenase in human breast cancer cells. Estrone sulfatase activity is also inhibited by norelgestromin, a norgestimate metabolite. Interesting information was obtained with a similar progestogen, tibolone, which is rapidly metabolized into the active 3α/3β-hydroxy and 4-ene metabolites. All these metabolites can inhibit sulfatase and 17β-hydroxysteroid dehydrogenase and stimulate sulfotransferase in human breast cancer cells. Another attractive aspect is the metabolic transformation of progesterone itself in human breast tissues. In the normal breast progesterone is mainly converted to 4-ene derivatives, whereas in the tumor tissue it is converted mostly to 5α-pregnane derivatives. 20α-Dihydroprogesterone is found mainly in normal breast tissue and possesses antiproliferative properties as well as the ability to act as an anti-aromatase agent. Consequently, this progesterone metabolite could be involved in the control of estradiol production in the normal breast and therefore implicated in one of the multifactorial mechanisms of the breast carcinogenesis process. In conclusion, a better understanding of both natural and synthetic hormone metabolic transformations and their control could potentially provide

  12. Optical determination of the hemoglobin oxygenation state of breast biopsies and human breast cancer xenografts in nude mice

    Science.gov (United States)

    Marks, Fay A.

    1992-05-01

    Differences in the oxygenation state of benign and malignant breast biopsies, and human breast cancer xenografts in immune-deficient mice were monitored using a spectrophotometer with integrating sphere. The breast biopsies were maintained below -50 degree(s)C and the mouse model tumors maintained in growth medium at 0 degree(s)C. Tissue sections 500 (mu) thick were allowed to come up to room temperature for mounting between quartz slides and were evaluated over the wavelength region 240 - 2500 nm. Data collection was done within 10 minutes of the removal of the biopsies from storage and, within 5 minutes for the xenografts. That this preparation protocol allowed us to study the samples very close to the in- vivo state was evident from the lack of deoxyhemoglobin in the benign samples. Component analysis performed in the 300 - 800 nm region showed that the malignant samples contained predominantly deoxygenated blood while the benign samples exhibited oxyhemoglobin signature. Absorption peaks due to fat and traces of bilirubin were also resolved in some of the samples. Assuming that the samples are very nearly representative of the in-vivo condition, these hemoglobin differences may well serve as a basis for imaging tumors or, for tissue characterization in a minimally invasive environment.

  13. Does dietary iodine regulate oxidative stress and adiponectin levels in human breast milk?

    Science.gov (United States)

    Gutiérrez-Repiso, Carolina; Velasco, Inés; Garcia-Escobar, Eva; Garcia-Serrano, Sara; Rodríguez-Pacheco, Francisca; Linares, Francisca; Ruiz de Adana, Maria Soledad; Rubio-Martin, Elehazara; Garrido-Sanchez, Lourdes; Cobos-Bravo, Juan Francisco; Priego-Puga, Tatiana; Rojo-Martinez, Gemma; Soriguer, Federico; García-Fuentes, Eduardo

    2014-02-10

    Little is known about the association between iodine and human milk composition. In this study, we investigated the association between iodine and different markers of oxidative stress and obesity-related hormones in human breast milk. This work is composed of two cross-sectional studies (in lactating women and in the general population), one prospective and one in vitro. In the cross-sectional study in lactating women, the breast milk iodine correlated negatively with superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) activities, and with adiponectin levels. An in vitro culture of human adipocytes with 1 μM potassium iodide (KI, dose similar to the human breast milk iodine concentration) produced a significant decrease in adiponectin, GSH-Px, SOD1, and SOD2 mRNA expression. However, after 2 months of treatment with KI in the prospective study, a positive correlation was found between 24-h urinary iodine and serum adiponectin. Our observations lead to the hypothesis that iodine may be a factor directly involved in the regulation of oxidative stress and adiponectin levels in human breast milk.

  14. 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......-II), but not transforming growth factor beta-I (TGF-beta1). Of these, IGF-II is the only peptide whose expression is altered by endocrine therapy. Treatment of T61-bearing nude mice with physiologic doses of estrogen is accompanied by loss of IGF-II mRNA expression within 24 hours, and rapid regression of tumor. T61 tumor...

  15. Quantitative determination of the human breast milk macronutrients by near-infrared Raman spectroscopy

    Science.gov (United States)

    Motta, Edlene d. C. M.; Zângaro, Renato A.; Silveira, Landulfo, Jr.

    2012-03-01

    This work proposes the evaluation of the macronutrient constitution of human breast milk based on the spectral information provided by near-infrared Raman spectroscopy. Human breast milk (5 mL) from a subject was collected during the first two weeks of breastfeeding and stocked in -20°C freezer. Raman spectra were measured using a Raman spectrometer (830 nm excitation) coupled to a fiber based Raman probe. Spectra of human milk were dominated by bands of proteins, lipids and carbohydrates in the 600-1800 cm-1 spectral region. Raman spectroscopy revealed differences in the biochemical constitution of human milk depending on the time of breastfeeding startup. This technique could be employed to develop a classification routine for the milk in Human Milk Banking (HMB) depending on the nutritional facts.

  16. Plasma membrane proteomics of human breast cancer cell lines identifies potential targets for breast cancer diagnosis and treatment.

    Directory of Open Access Journals (Sweden)

    Yvonne S Ziegler

    Full Text Available The use of broad spectrum chemotherapeutic agents to treat breast cancer results in substantial and debilitating side effects, necessitating the development of targeted therapies to limit tumor proliferation and prevent metastasis. In recent years, the list of approved targeted therapies has expanded, and it includes both monoclonal antibodies and small molecule inhibitors that interfere with key proteins involved in the uncontrolled growth and migration of cancer cells. The targeting of plasma membrane proteins has been most successful to date, and this is reflected in the large representation of these proteins as targets of newer therapies. In view of these facts, experiments were designed to investigate the plasma membrane proteome of a variety of human breast cancer cell lines representing hormone-responsive, ErbB2 over-expressing and triple negative cell types, as well as a benign control. Plasma membranes were isolated by using an aqueous two-phase system, and the resulting proteins were subjected to mass spectrometry analysis. Overall, each of the cell lines expressed some unique proteins, and a number of proteins were expressed in multiple cell lines, but in patterns that did not always follow traditional clinical definitions of breast cancer type. From our data, it can be deduced that most cancer cells possess multiple strategies to promote uncontrolled growth, reflected in aberrant expression of tyrosine kinases, cellular adhesion molecules, and structural proteins. Our data set provides a very rich and complex picture of plasma membrane proteins present on breast cancer cells, and the sorting and categorizing of this data provides interesting insights into the biology, classification, and potential treatment of this prevalent and debilitating disease.

  17. Long non-coding RNA TUG1 promotes cell proliferation and metastasis in human breast cancer.

    Science.gov (United States)

    Li, Teng; Liu, Yun; Xiao, Haifeng; Xu, Guanghui

    2017-07-01

    Long non-coding RNAs (LncRNAs) utilize a wide variety of mechanisms to regulate RNAs or proteins on the transcriptional or post-transcriptional levels. Accumulating studies have identified numerous LncRNAs to exert critical effects on different physiological processes, genetic disorders, and human diseases. Both clinical tissues from breast cancer patients and cultured cells were used for the qRT-PCR analysis. Specific siRNAs were included to assess the roles of TUG1 with cell viability assay, transwell assay, and cell apoptosis assay, respectively. The expression of TUG1 was enhanced in breast cancerous tissues and in highly invasive breast cancer cell lines and was associated with clinical variables, including tumor size, distant metastasis and TNM staging. Knockdown of TUG1 significantly slowed down cell proliferation, cell migration, and invasion in breast cancer cell lines MDA-MB-231 and MDA-MB-436. In addition, cell apoptotic rate was shown to increase upon siTUG1 treatment as evidenced by increases of the activities of caspase-3 and caspase-9. The identification of TUG1 as a critical mediator of breast cancer progression implied that it might serve as a biomarker for the diagnosis and treatment of breast cancer in clinic.

  18. Human sodium iodide symporter (hNIS) in fibroadenoma breast--a immunohistochemical study.

    Science.gov (United States)

    Rai, Ruchi; Shrivastava, Ashutosh; Tandon, Ashwani; Godbole, Madan M; Kumar, Sandeep; Das, Vinita; Dwivedi, Varsha; Pal, Lily

    2011-02-01

    Human sodium iodide symporter (hNIS), responsible for the active transport of iodine is an integral plasma membrane glycoprotein present in the thyroid cells and extrathyroid tissues like breast and salivary glands. If its functional form is unequivocally shown in benign or malignant breast tissues, then it may serve as a basis for diagnosis and treatment using radioactive iodine. With an aim to analyze the hNIS expression in a distinct benign breast condition of fibroadenoma, biopsy proven fibroadenoma tissues, normal non-lactating breast tissue and biopsy proven infiltrating duct carcinoma tissues were examined for hNIS expression using immunohistochemistry. Out of 20 biopsy proven fibroadenoma tissues, 19 (95%) showed positivity for hNIS protein and only one was negative. Of these 10% were mildly positive, 50% cases were moderately positive and 35% showed intense positivity. None of the control tissue obtained from reduction mammoplasty specimens or normal breast tissues samples (5 cms away from the tumor) were positive, hNIS was also intensely positive in 9 out of 10 (90%) infiltrating duct carcinoma tissues and moderately positive in one case. These preliminary results show that hNIS was present in high frequency as demonstrated by immunohistochemistry in fibroadenoma breast.

  19. Presence of human papilloma virus in a series of breast carcinoma from Argentina.

    Directory of Open Access Journals (Sweden)

    Ana Laura Pereira Suarez

    Full Text Available The etiology and the molecular mechanisms related to breast carcinogenesis remain poorly understood. Some recent reports have examined the role of Human Papillomavirus (HPV in this disease. The purpose of this study was to determine the prevalence of HPV in breast cancer.Sixty one fresh frozen breast cancers samples were analyzed. Samples were tested for HPV by PCR, and products were automatically sequenced. Findings were correlated with clinical and pathological characteristics.The HPV DNA prevalence in the breast cancer samples was 26% (16/61. Clinical parameters were not statistically associated with HPV presence (p>0.05 χ(2 test. Sequence analysis in a subgroup of cases indicates the prevalence of low risk HPV11, followed by high risk HPV16. We found no HPV transcriptional activity.The present study demonstrated for the first time in Argentina the presence of HPV in a proportion of the malignant breast tissues. This finding suggests that HPV may have a biological significance in breast carcinogenesis.

  20. The Acinar Cage: Basement Membranes Determine Molecule Exchange and Mechanical Stability of Human Breast Cell Acini.

    Directory of Open Access Journals (Sweden)

    Aljona Gaiko-Shcherbak

    Full Text Available The biophysical properties of the basement membrane that surrounds human breast glands are poorly understood, but are thought to be decisive for normal organ function and malignancy. Here, we characterize the breast gland basement membrane with a focus on molecule permeation and mechanical stability, both crucial for organ function. We used well-established and nature-mimicking MCF10A acini as 3D cell model for human breast glands, with ether low- or highly-developed basement membrane scaffolds. Semi-quantitative dextran tracer (3 to 40 kDa experiments allowed us to investigate the basement membrane scaffold as a molecule diffusion barrier in human breast acini in vitro. We demonstrated that molecule permeation correlated positively with macromolecule size and intriguingly also with basement membrane development state, revealing a pore size of at least 9 nm. Notably, an intact collagen IV mesh proved to be essential for this permeation function. Furthermore, we performed ultra-sensitive atomic force microscopy to quantify the response of native breast acini and of decellularized basement membrane shells against mechanical indentation. We found a clear correlation between increasing acinar force resistance and basement membrane formation stage. Most important native acini with highly-developed basement membranes as well as cell-free basement membrane shells could both withstand physiologically relevant loads (≤ 20 nN without loss of structural integrity. In contrast, low-developed basement membranes were significantly softer and more fragile. In conclusion, our study emphasizes the key role of the basement membrane as conductor of acinar molecule influx and mechanical stability of human breast glands, which are fundamental for normal organ function.

  1. Antiandrogenic actions of medroxyprogesterone acetate on epithelial cells within normal human breast tissues cultured ex vivo.

    Science.gov (United States)

    Ochnik, Aleksandra M; Moore, Nicole L; Jankovic-Karasoulos, Tanja; Bianco-Miotto, Tina; Ryan, Natalie K; Thomas, Mervyn R; Birrell, Stephen N; Butler, Lisa M; Tilley, Wayne D; Hickey, Theresa E

    2014-01-01

    Medroxyprogesterone acetate (MPA), a component of combined estrogen-progestin therapy (EPT), has been associated with increased breast cancer risk in EPT users. MPA can bind to the androgen receptor (AR), and AR signaling inhibits cell growth in breast tissues. Therefore, the aim of this study was to investigate the potential of MPA to disrupt AR signaling in an ex vivo culture model of normal human breast tissue. Histologically normal breast tissues from women undergoing breast surgical operation were cultured in the presence or in the absence of the native AR ligand 5α-dihydrotestosterone (DHT), MPA, or the AR antagonist bicalutamide. Ki67, bromodeoxyuridine, B-cell CLL/lymphoma 2 (BCL2), AR, estrogen receptor α, and progesterone receptor were detected by immunohistochemistry. DHT inhibited the proliferation of breast epithelial cells in an AR-dependent manner within tissues from postmenopausal women, and MPA significantly antagonized this androgenic effect. These hormonal responses were not commonly observed in cultured tissues from premenopausal women. In tissues from postmenopausal women, DHT either induced or repressed BCL2 expression, and the antiandrogenic effect of MPA on BCL2 was variable. MPA significantly opposed the positive effect of DHT on AR stabilization, but these hormones had no significant effect on estrogen receptor α or progesterone receptor levels. In a subset of postmenopausal women, MPA exerts an antiandrogenic effect on breast epithelial cells that is associated with increased proliferation and destabilization of AR protein. This activity may contribute mechanistically to the increased risk of breast cancer in women taking MPA-containing EPT.

  2. High-risk human papillomavirus (HPV) DNA sequences in metaplastic breast carcinomas of Mexican women

    International Nuclear Information System (INIS)

    Herrera-Goepfert, Roberto; Vela-Chávez, Teresa; Carrillo-García, Adela; Lizano-Soberón, Marcela; Amador-Molina, Alfredo; Oñate-Ocaña, Luis F; Hallmann, Rita Sotelo-Regil

    2013-01-01

    Metaplastic carcinoma, an uncommon subtype of breast cancer, is part of the spectrum of basal-like, triple receptor-negative breast carcinomas. The present study examined 20 surgical specimens of metaplastic breast carcinomas, for the presence of high-risk Human papillomavirus (HPV), which is suspected to be a potential carcinogenic agent for breast carcinoma. Mastectomy specimens from patients harboring metaplastic breast carcinoma, as defined by the World Health Organization (WHO), and who attended the Instituto Nacional de Cancerologia in Mexico City, were retrieved from the files of the Department of Pathology accumulated during a 16-year period (1995–2008). Demographic and clinical information was obtained from patients’ medical records. DNA was extracted from formalin-fixed, paraffin-embedded tumors and HPV type-specific amplification was performed by means of Polymerase chain reaction (PCR). Quantitative Real-time (RT) PCR was conducted in HPV positive cases. Statistically, the association of continuous or categorical variables with HPV status was tested by the Student t, the Chi square, or Fisher’s exact tests, as appropriate. High-risk HPV DNA was detected in eight (40%) of 20 metaplastic breast carcinomas: seven (87.5%) HPV-16 and one (12.5%) HPV-18. Mean age of patients with HPV-positive cases was 49 years (range 24–72 years), the same as for HPV-negative cases (range, 30–73 years). There were not striking differences between HPV + and HPV– metaplastic carcinomas regarding clinical findings. Nearly all cases were negative for estrogen, progesterone and Human epidermal growth factor receptor 2 (HER2), but positive for Epidermal growth factor receptor (EGFR). High-risk HPV has been strongly associated with conventional breast carcinomas, although the subtle mechanism of neoplastic transformation is poorly understood. In Mexican patients, the prevalence of HPV infection among metaplastic breast carcinomas is higher than in non-metaplastic ones

  3. Breast-feeding and human immunodeficiency virus infection: assessment of knowledge among clinicians in Kenya.

    Science.gov (United States)

    Murila, Florence; Obimbo, Moses M; Musoke, Rachel; Tsikhutsu, Isaac; Migiro, Santau; Ogeng'o, Julius

    2015-02-01

    In Kenya, human immunodeficiency virus (HIV) prevalence ranks among the highest in the world. Approximately 60 000 infections yearly are attributed to vertical transmission including the process of labour and breast-feeding. The vast of the population affected is in the developing world. Clinical officers and nurses play an important role in provision of primary health care to antenatal and postnatal mothers. There are a few studies that have explored the clinicians' knowledge on breast-feeding in the face of HIV and in relation to vertical transmission this being a vital component in prevention of maternal-to-child transmission. The aim of this study was to evaluate clinicians' knowledge on HIV in relation to breast-feeding in Kenya. A cross-sectional survey was conducted to assess knowledge of 161 clinical officers and nurses serving in the maternity and children' wards in various hospitals in Kenya. The participants were derived from all district and provincial referral facilities in Kenya. A preformatted questionnaire containing a series of questions on HIV and breast-feeding was administered to clinicians who were then scored and analyzed. All the 161 participants responded. Majority of clinicians (92%) were knowledgeable regarding prevention of mother-to-child transmission. Regarding HIV and breast-feeding, 49.7% thought expressed breast milk from HIV-positive mothers should be heated before being given. Majority (78.3%) thought breast milk should be given regardless of availability of alternatives. According to 74.5% of the participants, exclusive breast-feeding increased chances of HIV transmission. Two-thirds (66.5%) would recommend breast-feeding for mothers who do not know their HIV status (66.5%). This study observes that a majority of the clinicians have inadequate knowledge on breast-feeding in the face of HIV. There is need to promote training programmes on breast-feeding and transmission of HIV from mother to child. This can be done as in

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

    Science.gov (United States)

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

  5. Epstein-Barr virus, human papillomavirus and mouse mammary tumour virus as multiple viruses in breast cancer.

    Science.gov (United States)

    Glenn, Wendy K; Heng, Benjamin; Delprado, Warick; Iacopetta, Barry; Whitaker, Noel J; Lawson, James S

    2012-01-01

    The purpose of this investigation is to determine if Epstein Barr virus (EBV), high risk human papillomavirus (HPV), and mouse mammary tumour viruses (MMTV) co-exist in some breast cancers. All the specimens were from women residing in Australia. For investigations based on standard PCR, we used fresh frozen DNA extracts from 50 unselected invasive breast cancers. For normal breast specimens, we used DNA extracts from epithelial cells from milk donated by 40 lactating women. For investigations based on in situ PCR we used 27 unselected archival formalin fixed breast cancer specimens and 18 unselected archival formalin fixed normal breast specimens from women who had breast reduction surgery. Thirteen of these fixed breast cancer specimens were ductal carcinoma in situ (dcis) and 14 were predominantly invasive ductal carcinomas (idc). EBV sequences were identified in 68%, high risk HPV sequences in 50%, and MMTV sequences in 78% of DNA extracted from 50 invasive breast cancer specimens. These same viruses were identified in selected normal and breast cancer specimens by in situ PCR. Sequences from more than one viral type were identified in 72% of the same breast cancer specimens. Normal controls showed these viruses were also present in epithelial cells in human milk - EBV (35%), HPV, 20%) and MMTV (32%) of 40 milk samples from normal lactating women, with multiple viruses being identified in 13% of the same milk samples. We conclude that (i) EBV, HPV and MMTV gene sequences are present and co-exist in many human breast cancers, (ii) the presence of these viruses in breast cancer is associated with young age of diagnosis and possibly an increased grade of breast cancer.

  6. Characterization and discrimination of human breast cancer and normal breast tissues using resonance Raman spectroscopy

    Science.gov (United States)

    Wu, Binlin; Smith, Jason; Zhang, Lin; Gao, Xin; Alfano, Robert R.

    2018-02-01

    Worldwide breast cancer incidence has increased by more than twenty percent in the past decade. It is also known that in that time, mortality due to the affliction has increased by fourteen percent. Using optical-based diagnostic techniques, such as Raman spectroscopy, has been explored in order to increase diagnostic accuracy in a more objective way along with significantly decreasing diagnostic wait-times. In this study, Raman spectroscopy with 532-nm excitation was used in order to incite resonance effects to enhance Stokes Raman scattering from unique biomolecular vibrational modes. Seventy-two Raman spectra (41 cancerous, 31 normal) were collected from nine breast tissue samples by performing a ten-spectra average using a 500-ms acquisition time at each acquisition location. The raw spectral data was subsequently prepared for analysis with background correction and normalization. The spectral data in the Raman Shift range of 750- 2000 cm-1 was used for analysis since the detector has highest sensitivity around in this range. The matrix decomposition technique nonnegative matrix factorization (NMF) was then performed on this processed data. The resulting leave-oneout cross-validation using two selective feature components resulted in sensitivity, specificity and accuracy of 92.6%, 100% and 96.0% respectively. The performance of NMF was also compared to that using principal component analysis (PCA), and NMF was shown be to be superior to PCA in this study. This study shows that coupling the resonance Raman spectroscopy technique with subsequent NMF decomposition method shows potential for high characterization accuracy in breast cancer detection.

  7. Threshold analysis and biodistribution of fluorescently labeled bevacizumab in human breast cancer

    NARCIS (Netherlands)

    Koch, Maximillian; de Jong, Johannes S; Glatz, Jürgen; Symvoulidis, Panagiotis; Lamberts, Laetitia E; Adams, Arthur; Kranendonk, Mariëtte E G; Terwisscha van Scheltinga, Anton G T; Aichler, Michaela; Jansen, Liesbeth; de Vries, Jakob; Lub-de Hooge, Marjolijn N; Schröder, Carolina P; Jorritsma-Smit, Annelies; Linssen, Matthijs D; de Boer, Esther; van der Vegt, Bert; Nagengast, Wouter B; Elias, Sjoerd G; Oliveira, Sabrina; Witkamp, Arjen; Mali, Willem P Th M; van der Wall, Elsken; Garcia-Allende, Beatriz P; Van Diest, Paul J; de Vries, Elisabeth G; Walch, Axel; van Dam, Gooitzen M; Ntziachristos, Vasilis

    2017-01-01

    In vivo tumor labeling with fluorescent agents may assist endoscopic and surgical guidance for cancer therapy as well as create opportunities to directly observe cancer biology in patients. However, malignant and non-malignant tissues are usually distinguished on fluorescence images by applying

  8. Threshold analysis and biodistribution of fluorescently labeled bevacizumab in human breast cancer

    NARCIS (Netherlands)

    Koch, Maximillian; de Jong, Johannes S; Glatz, Jürgen; Symvoulidis, Panagiotis; Lamberts, Laetitia E; Adams, Arthur; Kranendonk, Mariëtte E G; Terwisscha van Scheltinga, Anton G T; Aichler, Michaela; Jansen, Liesbeth; de Vries, Jakob; Lub-de Hooge, Marjolijn N; Schröder, Carolina P; Jorritsma-Smit, Annelies; Linssen, Matthijs D; de Boer, Esther; van der Vegt, Bert; Nagengast, Wouter B; Elias, Sjoerd G; Oliveira, Sabrina|info:eu-repo/dai/nl/304841455; Witkamp, Arjen; Mali, Willem P Th M; van der Wall, Elsken; Garcia-Allende, Beatriz P; Van Diest, Paul J; de Vries, Elisabeth G; Walch, Axel; van Dam, Gooitzen M; Ntziachristos, Vasilis

    2016-01-01

    In vivo tumor labeling with fluorescent agents may assist endoscopic and surgical guidance for cancer therapy as well as create opportunities to directly observe cancer biology in patients. However, malignant and non-malignant tissues are usually distinguished on fluorescence images by applying

  9. Hybrid clone cells derived from human breast epithelial cells and human breast cancer cells exhibit properties of cancer stem/initiating cells.

    Science.gov (United States)

    Gauck, Daria; Keil, Silvia; Niggemann, Bernd; Zänker, Kurt S; Dittmar, Thomas

    2017-08-02

    The biological phenomenon of cell fusion has been associated with cancer progression since it was determined that normal cell × tumor cell fusion-derived hybrid cells could exhibit novel properties, such as enhanced metastatogenic capacity or increased drug resistance, and even as a mechanism that could give rise to cancer stem/initiating cells (CS/ICs). CS/ICs have been proposed as cancer cells that exhibit stem cell properties, including the ability to (re)initiate tumor growth. Five M13HS hybrid clone cells, which originated from spontaneous cell fusion events between M13SV1-EGFP-Neo human breast epithelial cells and HS578T-Hyg human breast cancer cells, and their parental cells were analyzed for expression of stemness and EMT-related marker proteins by Western blot analysis and confocal laser scanning microscopy. The frequency of ALDH1-positive cells was determined by flow cytometry using AldeRed fluorescent dye. Concurrently, the cells' colony forming capabilities as well as the cells' abilities to form mammospheres were investigated. The migratory activity of the cells was analyzed using a 3D collagen matrix migration assay. M13HS hybrid clone cells co-expressed SOX9, SLUG, CK8 and CK14, which were differently expressed in parental cells. A variation in the ALDH1-positive putative stem cell population was observed among the five hybrids ranging from 1.44% (M13HS-7) to 13.68% (M13HS-2). In comparison to the parental cells, all five hybrid clone cells possessed increased but also unique colony formation and mammosphere formation capabilities. M13HS-4 hybrid clone cells exhibited the highest colony formation capacity and second highest mammosphere formation capacity of all hybrids, whereby the mean diameter of the mammospheres was comparable to the parental cells. In contrast, the largest mammospheres originated from the M13HS-2 hybrid clone cells, whereas these cells' mammosphere formation capacity was comparable to the parental breast cancer cells. All M13HS

  10. Diaper dermatitis care of newborns human breast milk or barrier cream.

    Science.gov (United States)

    Gozen, Duygu; Caglar, Seda; Bayraktar, Sema; Atici, Funda

    2014-02-01

    To establish the effectiveness of human breast milk and barrier cream (40% zinc oxide with cod liver oil formulation) applied for the skincare of newborns in the neonatal intensive care unit on the healing process of diaper dermatitis. Diaper dermatitis is the most common dermatological condition in newborns who are cared for in the neonatal intensive care unit. Recently, there are several kinds of complementary skincare methods suggested for newborns, such as sunflower oil, human breast milk, etc. Also, some chemical formulations are still being used in many neonatal intensive care units. Randomised controlled, prospective, experimental. This study was carried out with a population including term and preterm newborns who developed diaper rash while being treated in the neonatal intensive care unit of a university hospital in Istanbul between February-October 2010. On completion of the research, a total of 63 newborns from human breast milk (n = 30) and barrier cream (n = 33) groups were contacted. Genders, mean gestation weeks, feeding method, antibiotic use, diaper area cleansing methods, diaper brands and prelesion scores of newborns in both groups were found to be comparable (p > 0·05). There was no statistically significant difference (p = 0.294) between the groups in terms of mean number of clinical improvement days, but postlesion score of the barrier cream group was statistically significantly lower (p = 0·002) than the human breast milk group. Barrier cream delivers more effective results than treatment with human breast milk, particularly in the treatment of newborns with moderate to severe dermatitis in the result of the study. This study will shed light on nursing care of skin for newborns who are treated in neonatal intensive care unit. © 2013 Blackwell Publishing Ltd.

  11. Inactivation of Zika virus in human breast milk by prolonged storage or pasteurization

    OpenAIRE

    Pfaender, Stephanie; Vielle, Nathalie J.; Ebert, Nadine; Steinmann, Eike; Alves, Marco P.; Thiel, Volker

    2017-01-01

    Zika virus infection during pregnancy poses a serious risk for pregnant women as it can cause severe birth defects. Even though the virus is mainly transmitted via mosquitos, human-to-human transmission has been described. Infectious viral particles have been detected in breast milk of infected women which raised concerns regarding the safety of breastfeeding in areas of Zika virus transmission or in case of a suspected or confirmed Zika virus infection. In this study, we show that Zika virus...

  12. Conjugated linoleic acid induces apoptosis through estrogen receptor alpha in human breast tissue

    Directory of Open Access Journals (Sweden)

    Liu Suling

    2008-07-01

    Full Text Available Abstract Background Conjugated linoleic acid (CLA, a naturally occurring fatty acid found in ruminant products such as milk and beef, has been shown to possess anti-cancer activities in in vivo animal models and in vitro cell culture systems. In human breast cancer, the overall duration of estrogen exposure is the most important risk factor for developing estrogen-responsive breast cancer. Accordingly, it has been suggested that estrogen exposure reduces apoptosis through the up-regulation of the anti-apoptosis protein, Bcl-2. Bcl-2, an anti-apoptotic protein, regulates apoptosis and plays a crucial role in the development and growth regulation of normal and cancerous cells. Our research interest is to examine the effects of CLA on the induction of apoptosis in human breast tissues. Methods The localization of Bcl-2 in both normal and cancerous human breast tissues was determined by immunohistochemical staining and the Bcl-2 protein expression was tested by western blot analysis. Co-culture of epithelial cells and stromal cells was carried out in the presence or absence of CLA to evaluate apoptosis in the context of a cell-cell interaction. Results The results showed that both normal and cancerous breast tissues were positive for Bcl-2 staining, which was higher overall in mammary ducts but very low in the surrounding stromal compartment. Interestingly, by quantifying the western blot data, basal Bcl-2 protein levels were higher in normal breast epithelial cells than in cancerous epithelial cells. Furthermore, treatment with 17β-estradiol (E2 stimulated growth and up-regulated Bcl-2 expression in estrogen responsive breast epithelial cells; however, these carcinogenic effects were diminished by either CLA or 4-Hydroxytamoxifen (Tam and were suppressed further by the combination of CLA and Tam. In both one cell type cultured and co-culture systems, CLA induced cell apoptosis in ERα transfected MDA-MB-231 cells but not in the wild type MDA

  13. Conjugated linoleic acid induces apoptosis through estrogen receptor alpha in human breast tissue

    International Nuclear Information System (INIS)

    Wang, Li-Shu; Huang, Yi-Wen; Liu, Suling; Yan, Pearlly; Lin, Young C

    2008-01-01

    Conjugated linoleic acid (CLA), a naturally occurring fatty acid found in ruminant products such as milk and beef, has been shown to possess anti-cancer activities in in vivo animal models and in vitro cell culture systems. In human breast cancer, the overall duration of estrogen exposure is the most important risk factor for developing estrogen-responsive breast cancer. Accordingly, it has been suggested that estrogen exposure reduces apoptosis through the up-regulation of the anti-apoptosis protein, Bcl-2. Bcl-2, an anti-apoptotic protein, regulates apoptosis and plays a crucial role in the development and growth regulation of normal and cancerous cells. Our research interest is to examine the effects of CLA on the induction of apoptosis in human breast tissues. The localization of Bcl-2 in both normal and cancerous human breast tissues was determined by immunohistochemical staining and the Bcl-2 protein expression was tested by western blot analysis. Co-culture of epithelial cells and stromal cells was carried out in the presence or absence of CLA to evaluate apoptosis in the context of a cell-cell interaction. The results showed that both normal and cancerous breast tissues were positive for Bcl-2 staining, which was higher overall in mammary ducts but very low in the surrounding stromal compartment. Interestingly, by quantifying the western blot data, basal Bcl-2 protein levels were higher in normal breast epithelial cells than in cancerous epithelial cells. Furthermore, treatment with 17β-estradiol (E 2 ) stimulated growth and up-regulated Bcl-2 expression in estrogen responsive breast epithelial cells; however, these carcinogenic effects were diminished by either CLA or 4-Hydroxytamoxifen (Tam) and were suppressed further by the combination of CLA and Tam. In both one cell type cultured and co-culture systems, CLA induced cell apoptosis in ERα transfected MDA-MB-231 cells but not in the wild type MDA-MB-231 cells. These data, therefore, demonstrate that

  14. Production and characterisation of monoclonal antibodies against RAI3 and its expression in human breast cancer

    International Nuclear Information System (INIS)

    Jörißen, Hannah; Klockenbring, Torsten; Bektas, Nuran; Dahl, Edgar; Hartmann, Arndt; Haaf, Anette ten; Di Fiore, Stefano; Kiefer, Hans; Thess, Andreas; Barth, Stefan

    2009-01-01

    RAI3 is an orphan G-protein coupled receptor (GPCR) that has been associated with malignancy and may play a role in the proliferation of breast cancer cells. Although its exact function in normal and malignant cells remains unclear and evidence supporting its role in oncogenesis is controversial, its abundant expression on the surface of cancer cells would make it an interesting target for the development of antibody-based therapeutics. To investigate the link with cancer and provide more evidence for its role, we carried out a systematic analysis of RAI3 expression in a large set of human breast cancer specimens. We expressed recombinant human RAI3 in bacteria and reconstituted the purified protein in liposomes to raise monoclonal antibodies using classical hybridoma techniques. The specific binding activity of the antibodies was confirmed by enzyme-linked immunosorbent assay (ELISA), western blot and immunocytochemistry. We carried out a systematic immunohistochemical analysis of RAI3 expression in human invasive breast carcinomas (n = 147) and normal breast tissues (n = 44) using a tissue microarray. In addition, a cDNA dot blot hybridisation assay was used to investigate a set of matched normal and cancerous breast tissue specimens (n = 50) as well as lymph node metastases (n = 3) for RAI3 mRNA expression. The anti-RAI3 monoclonal antibodies bound to recombinant human RAI3 protein with high specificity and affinity, as shown by ELISA, western blot and ICC. The cDNA dot blot and immunohistochemical experiments showed that both RAI3 mRNA and RAI3 protein were abundantly expressed in human breast carcinoma. However, there was no association between RAI3 protein expression and prognosis based on overall and recurrence-free survival. We have generated a novel, highly-specific monoclonal antibody that detects RAI3 in formaldehyde-fixed paraffin-embedded tissue. This is the first study to report a systematic analysis of RAI3 expression in normal and cancerous human

  15. Multidisciplinary Analysis of Cyclophilin A Function in Human Breast Cancer

    Science.gov (United States)

    2011-03-01

    following washing and medium change; at concen- trations of z30 Ag/mL, these effects were not reversible and cell death ensued (data not shown). To assess...ml) inhibiting proliferation and higher doses (30 mg CsA/ml and above) inducing cell death [50]. CsA treatment also decreased breast cancer cell...Genes Dev. 11, 167–178 7 Horseman , N.D. et al. (1997) Defective mammopoiesis, but normal hematopoiesis, in mice with a targeted disruption of the

  16. Expression of matrix metalloproteinases (MMPs) in primary human breast cancer and breast cancer cell lines: New findings and review of the literature

    International Nuclear Information System (INIS)

    Köhrmann, Andrea; Kammerer, Ulrike; Kapp, Michaela; Dietl, Johannes; Anacker, Jelena

    2009-01-01

    Matrix metalloproteinases (MMPs) are a family of structural and functional related endopeptidases. They play a crucial role in tumor invasion and building of metastatic formations because of their ability to degrade extracellular matrix proteins. Under physiological conditions their activity is precisely regulated in order to prevent tissue disruption. This physiological balance seems to be disrupted in cancer making tumor cells capable of invading the tissue. In breast cancer different expression levels of several MMPs have been found. To fill the gap in our knowledge about MMP expression in breast cancer, we analyzed the expression of all known human MMPs in a panel of twenty-five tissue samples (five normal breast tissues, ten grade 2 (G2) and ten grade 3 (G3) breast cancer tissues). As we found different expression levels for several MMPs in normal breast and breast cancer tissue as well as depending on tumor grade, we additionally analyzed the expression of MMPs in four breast cancer cell lines (MCF-7, MDA-MB-468, BT 20, ZR 75/1) commonly used in research. The results could thus be used as model for further studies on human breast cancer. Expression analysis was performed on mRNA and protein level using semiquantitative RT-PCR, Western blot, immunohistochemistry and immunocytochemistry. In summary, we identified several MMPs (MMP-1, -2, -8, -9, -10, -11, -12, -13, -15, -19, -23, -24, -27 and -28) with a stronger expression in breast cancer tissue compared to normal breast tissue. Of those, expression of MMP-8, -10, -12 and -27 is related to tumor grade since it is higher in analyzed G3 compared to G2 tissue samples. In contrast, MMP-7 and MMP-27 mRNA showed a weaker expression in tumor samples compared to healthy tissue. In addition, we demonstrated that the four breast cancer cell lines examined, are constitutively expressing a wide variety of MMPs. Of those, MDA-MB-468 showed the strongest mRNA and protein expression for most of the MMPs analyzed. MMP-1, -2

  17. In situ identification of CD44+/CD24- cancer cells in primary human breast carcinomas.

    Directory of Open Access Journals (Sweden)

    Giuseppe Perrone

    Full Text Available Breast cancer cells with the CD44+/CD24- phenotype have been reported to be tumourigenic due to their enhanced capacity for cancer development and their self-renewal potential. The identification of human tumourigenic breast cancer cells in surgical samples has recently received increased attention due to the implications for prognosis and treatment, although limitations exist in the interpretation of these studies. To better identify the CD44+/CD24- cells in routine surgical specimens, 56 primary breast carcinoma cases were analysed by immunofluorescence and confocal microscopy, and the results were compared using flow cytometry analysis to correlate the amount and distribution of the CD44+/CD24- population with clinicopathological features. Using these methods, we showed that the breast carcinoma cells displayed four distinct sub-populations based on the expression pattern of CD44 and CD24. The CD44+/CD24- cells were found in 91% of breast tumours and constituted an average of 6.12% (range, 0.11%-21.23% of the tumour. A strong correlation was found between the percentage of CD44+/CD24- cells in primary tumours and distant metastasis development (p = 0.0001; in addition, there was an inverse significant association with ER and PGR status (p = 0.002 and p = 0.001, respectively. No relationship was evident with tumour size (T and regional lymph node (N status, differentiation grade, proliferative index or HER2 status. In a multivariate analysis, the percentage of CD44+/CD24- cancer cells was an independent factor related to metastasis development (p = 0.004. Our results indicate that confocal analysis of fluorescence-labelled breast cancer samples obtained at surgery is a reliable method to identify the CD44+/CD24- tumourigenic cell population, allowing for the stratification of breast cancer patients into two groups with substantially different relapse rates on the basis of CD44+/CD24- cell percentage.

  18. Visualization and tissue classification of human breast cancer images using ultrahigh-resolution OCT (Conference Presentation)

    Science.gov (United States)

    Yao, Xinwen; Gan, Yu; Chang, Ernest W.; Hibshoosh, Hanina; Feldman, Sheldon; Hendon, Christine P.

    2017-02-01

    We employed a home-built ultrahigh resolution (UHR) OCT system at 800nm to image human breast cancer sample ex vivo. The system has an axial resolution of 2.72µm and a lateral resolution of 5.52µm with an extended imaging range of 1.78mm. Over 900 UHR OCT volumes were generated on specimens from 23 breast cancer cases. With better spatial resolution, detailed structures in the breast tissue were better defined. Different types of breast cancer as well as healthy breast tissue can be well delineated from the UHR OCT images. To quantitatively evaluate the advantages of UHR OCT imaging of breast cancer, features derived from OCT intensity images were used as inputs to a machine learning model, the relevance vector machine. A trained machine learning model was employed to evaluate the performance of tissue classification based on UHR OCT images for differentiating tissue types in the breast samples, including adipose tissue, healthy stroma and cancerous region. For adipose tissue, grid-based local features were extracted from OCT intensity data, including standard deviation, entropy, and homogeneity. We showed that it was possible to enhance the classification performance on distinguishing fat tissue from non-fat tissue by using the UHR images when compared with the results based on OCT images from a commercial 1300 nm OCT system. For invasive ductal carcinoma (IDC) and normal stroma differentiation, the classification was based on frame-based features that portray signal penetration depth and tissue reflectivity. The confusing matrix indicated a sensitivity of 97.5% and a sensitivity of 77.8%.

  19. Prevalence of human papilloma virus among women with breast cancer since 2005-2009 in Isfahan

    Directory of Open Access Journals (Sweden)

    Leila Manzouri

    2014-01-01

    Full Text Available Background : Human papilloma virus (HPV DNA has been detected in breast carcinoma by different laboratorial techniques, suggesting that the virus could play a role in the pathogenesis of this tumor. Materials and Methods: It was a descriptive study. Systematic random sampling was used for selecting 55 cases of breast cancer and 51 controls of benign breast lesions from the file of Seyedshohada hospital of Isfahan since 2005-2009. A total of 106 paraffin-embedded specimens were selected and HPV DNA was analyzed by polymerase chain reaction and sequenced for different types of HPV in case of positivity for HPV DNA. Data analysis was performed by SPSS 16 software using descriptive statistic, Chi-square, and Fisher′s exact tests. Results: Out of 55 malignant and 51 benign breast specimens, 18.2% (10 and 13.7% (7 were positive to HPV DNA, respectively ( P = 0.53; 70% (7 malignant and 43% (3 benign breast specimens were positive to high-risk HPV genotypes. In malignant specimens, the most common high- and low-risk genotypes were HPV-16 (3.6% and HPV-11 (3.6%, respectively. In benign specimens, the most common high- and low-risk genotypes were HPV-31 (3.9% and HPV-43 (3.9%, respectively. Among malignant and benign specimens, ductal carcinoma and fibro adenoma were the most common lesions positive to different types of HPV, respectively. Conclusion: This study demonstrated the presence of HPV genome in both malignant and benign tumor tissues in women with breast lesions in Isfahan; therefore, further larger epidemiologic studies need to be analyzed to establish the exact role of this virus in the pathogenesis of breast cancer.

  20. Prevalence of human papilloma virus among women with breast cancer since 2005-2009 in Isfahan.

    Science.gov (United States)

    Manzouri, Leila; Salehi, Rasoul; Shariatpanahi, Shervin; Rezaie, Parisa

    2014-01-01

    Human papilloma virus (HPV) DNA has been detected in breast carcinoma by different laboratorial techniques, suggesting that the virus could play a role in the pathogenesis of this tumor. It was a descriptive study. Systematic random sampling was used for selecting 55 cases of breast cancer and 51 controls of benign breast lesions from the file of Seyedshohada hospital of Isfahan since 2005-2009. A total of 106 paraffin-embedded specimens were selected and HPV DNA was analyzed by polymerase chain reaction and sequenced for different types of HPV in case of positivity for HPV DNA. Data analysis was performed by SPSS 16 software using descriptive statistic, Chi-square, and Fisher's exact tests. Out of 55 malignant and 51 benign breast specimens, 18.2% (10) and 13.7% (7) were positive to HPV DNA, respectively (P = 0.53); 70% (7) malignant and 43% (3) benign breast specimens were positive to high-risk HPV genotypes. In malignant specimens, the most common high- and low-risk genotypes were HPV-16 (3.6%) and HPV-11 (3.6%), respectively. In benign specimens, the most common high- and low-risk genotypes were HPV-31 (3.9%) and HPV-43 (3.9%), respectively. Among malignant and benign specimens, ductal carcinoma and fibro adenoma were the most common lesions positive to different types of HPV, respectively. This study demonstrated the presence of HPV genome in both malignant and benign tumor tissues in women with breast lesions in Isfahan; therefore, further larger epidemiologic studies need to be analyzed to establish the exact role of this virus in the pathogenesis of breast cancer.

  1. The effects of erythropoietin signaling on telomerase regulation in non-erythroid malignant and non-malignant cells

    International Nuclear Information System (INIS)

    Uziel, Orit; Kanfer, Gil; Beery, Einat; Yelin, Dana; Shepshelovich, Daniel; Bakhanashvili, Mary; Nordenberg, Jardena; Lahav, Meir

    2014-01-01

    Highlights: • We assumed that some of erythropoietin adverse effects may be mediated by telomerase activity. • EPO administration increased telomerase activity, cells proliferation and migration. • The inhibition of telomerase modestly repressed the proliferative effect of erythropoietin. • Telomere shortening caused by long term inhibition of the enzyme totally abolished that effect. • This effect was mediated via the Lyn–AKT axis and not by the canonical JAK2–STAT pathway. - Abstract: Treatment with erythropoietin (EPO) in several cancers is associated with decreased survival due to cancer progression. Due to the major importance of telomerase in cancer biology we hypothesized that some of these effects may be mediated through EPO effect on telomerase. For this aim we explored the possible effects of EPO on telomerase regulation, cell migration and chemosensitivity in non-erythroid malignant and non-malignant cells. Cell proliferation, telomerase activity (TA) and cell migration increased in response to EPO. EPO had no effect on cancer cells sensitivity to cisplatinum and on the cell cycle status. The inhibition of telomerase modestly repressed the proliferative effect of EPO. Telomere shortening caused by long term inhibition of the enzyme abolished the effect of EPO, suggesting that EPO effects on cancer cells are related to telomere dynamics. TA was correlated with the levels of Epo-R. The increase in TA was mediated post-translationally through the Lyn-Src and not the canonical JAK2 pathway

  2. Occupational exposure to respirable crystalline silica and chronic non-malignant renal disease: systematic review and meta-analysis.

    Science.gov (United States)

    Möhner, Matthias; Pohrt, Anne; Gellissen, Johannes

    2017-10-01

    While occupational exposure to respirable silica is known to lead to lung disease, most notably silicosis, its association with chronic kidney disease is unclear. This review explores the association between occupational exposure to respirable silica and chronic non-malignant renal disease such as glomerulonephritis. The evidence has been collected and compiled. Possible sources of bias are thoroughly discussed. Cohort studies with silica exposure and case-control studies of renal disease were searched in PubMed until January 2015. Two authors independently abstracted data; any disagreement was resolved by consulting a third reviewer. A meta-analysis was performed to evaluate the association to silica exposure. A total of 23 cohort and four case-control studies were included in the analysis. The meta-analysis of cohort studies yielded elevated overall SMRs for renal disease. Some studies, however, included dose-response analyses, most of which did not show a positive trend. The approaches and results of the case-control studies were very heterogeneous. While the studies of cohorts exposed to silica found elevated SMRs for renal disease, no clear evidence of a dose-response relationship emerged. The elevated risk may be attributed to diagnostic and methodological issues. In order to permit a reliable estimation of a possible causal link, exposed cohorts should be monitored for renal disease, as the information from mortality studies is hardly reliable in this field.

  3. Non-myeloablative allogeneic stem cell transplantation focusing on immunotherapy of life-threatening malignant and non-malignant diseases.

    Science.gov (United States)

    Slavin, S; Nagler, A; Shapira, M; Panigrahi, S; Samuel, S; Or, A

    2001-01-01

    Allogeneic bone marrow transplantation (BMT) represents an important therapeutic tool for treatment of otherwise incurable malignant and non-malignant diseases. Until recently, myeloablative regimens were considered mandatory for eradication of all undesirable host-derived hematopoietic elements. Our preclinical and ongoing clinical studies indicated that much more effective eradication of host immunohematopoietic system cells could be achieved by adoptive allogeneic cell therapy with donor lymphocyte infusion (DLI) following BMT. Thus, eradication of blood cancer cells, especially in patients with CML can be frequently accomplished despite complete resistance of such tumor cells to maximally tolerated doses of chemoradiotherapy. Our cumulative experience suggested that graft versus leukemia (GVL) effects might be a useful tool for eradication of otherwise resistant tumor cells of host origin. The latter working hypothesis suggested that effective BMT procedures may be accomplished without lethal conditioning of the host, using new well tolerated non-myeloablative regimen, thus possibly minimizing immediate and late side effects related to myeloablative procedures considered until recently mandatory for conditioning of BMT recipients. Recent clinical data that will be presented suggests that safe non-myeloablative stem cell transplantation (NST), with no major toxicity can replace the conventional BMT. Thus, NST may provide an option for cure for a large spectrum of clinical indications in children and elderly individuals without lower or upper age limit, while minimizing procedure-related toxicity and mortality.

  4. The effects of erythropoietin signaling on telomerase regulation in non-erythroid malignant and non-malignant cells

    Energy Technology Data Exchange (ETDEWEB)

    Uziel, Orit, E-mail: Oritu@clalit.org.il [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Kanfer, Gil [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Dep. of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Beery, Einat [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Yelin, Dana; Shepshelovich, Daniel [Medicine A, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Bakhanashvili, Mary [Unit of Infectious Diseases, Sheba Medical Center, Tel-Hashomer (Israel); Nordenberg, Jardena [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Dep. of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Endocrinology Laboratory, Beilinson Medical Center, Petah-Tikva (Israel); Lahav, Meir [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Medicine A, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel)

    2014-07-18

    Highlights: • We assumed that some of erythropoietin adverse effects may be mediated by telomerase activity. • EPO administration increased telomerase activity, cells proliferation and migration. • The inhibition of telomerase modestly repressed the proliferative effect of erythropoietin. • Telomere shortening caused by long term inhibition of the enzyme totally abolished that effect. • This effect was mediated via the Lyn–AKT axis and not by the canonical JAK2–STAT pathway. - Abstract: Treatment with erythropoietin (EPO) in several cancers is associated with decreased survival due to cancer progression. Due to the major importance of telomerase in cancer biology we hypothesized that some of these effects may be mediated through EPO effect on telomerase. For this aim we explored the possible effects of EPO on telomerase regulation, cell migration and chemosensitivity in non-erythroid malignant and non-malignant cells. Cell proliferation, telomerase activity (TA) and cell migration increased in response to EPO. EPO had no effect on cancer cells sensitivity to cisplatinum and on the cell cycle status. The inhibition of telomerase modestly repressed the proliferative effect of EPO. Telomere shortening caused by long term inhibition of the enzyme abolished the effect of EPO, suggesting that EPO effects on cancer cells are related to telomere dynamics. TA was correlated with the levels of Epo-R. The increase in TA was mediated post-translationally through the Lyn-Src and not the canonical JAK2 pathway.

  5. Anticancer Effects of Different Seaweeds on Human Colon and Breast Cancers

    Directory of Open Access Journals (Sweden)

    Ghislain Moussavou

    2014-09-01

    Full Text Available Seafoods and seaweeds represent some of the most important reservoirs of new therapeutic compounds for humans. Seaweed has been shown to have several biological activities, including anticancer activity. This review focuses on colorectal and breast cancers, which are major causes of cancer-related mortality in men and women. It also describes various compounds extracted from a range of seaweeds that have been shown to eradicate or slow the progression of cancer. Fucoidan extracted from the brown algae Fucus spp. has shown activity against both colorectal and breast cancers. Furthermore, we review the mechanisms through which these compounds can induce apoptosis in vitro and in vivo. By considering the ability of compounds present in seaweeds to act against colorectal and breast cancers, this review highlights the potential use of seaweeds as anticancer agents.

  6. The lipid content of cisplatin- and doxorubicin-resistant MCF-7 human breast cancer cells.

    Science.gov (United States)

    Todor, I N; Lukyanova, N Yu; Chekhun, V F

    2012-07-01

    To perform the comparative study both of qualitative and quantitative content of lipids in parental and drug resistant breast cancer cells. Parental (MCF-7/S) and resistant to cisplatin (MCF-7/CP) and doxorubicin (MCF-7/Dox) human breast cancer cells were used in the study. Cholesterol, total lipids and phospholipids content were determined by means of thin-layer chromatography. It was found that cholesterol as well as cholesterol ethers content are significantly higher but diacylglycerols, triacyl-glycerols content are significantly lower in resistant cell strains than in parental (sensitive) cells. Moreover the analysis of individual phospholipids showed the increase of sphingomyelin, phosphatidylserine, cardiolipin, phosphatidic acid and the decrease of phosphatidy-lethanolamine, phosphatidylcholine in MCF-7/CP and MCF-7/Dox cells. Obtained results allow to suggest that the lipid profile changes can mediate the modulation of membrane fluidity in drug resistant MCF-7 breast cancer cells.

  7. Investigating the effects of Pentoxifylline on human breast cancer cells using Raman spectroscopy

    Directory of Open Access Journals (Sweden)

    Peeyush N. Goel

    2015-03-01

    Full Text Available Breast cancer is one of the leading causes of cancer-related deaths in a global scenario. In the present study, biochemical changes exerted upon Pentoxifylline (PTX treatment had been appraised in human breast cancer cells using Raman spectroscopy. There are no clinically approved methods to monitor such therapeutic responses available. The spectral profiling is suggestive of changes in DNA, protein and lipid contents showing a linear relationship with drug dosage. Further, multivariate analysis using principal-component based linear-discriminant-analysis (PC-LDA was employed for classifying the control and the PTX treated groups. These findings support the feasibility of Raman spectroscopy as an alternate/adjunct label-free, objective method for monitoring drug-induced modifications against breast cancer cells.

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

    Directory of Open Access Journals (Sweden)

    Marijke I. Zonneveld

    2014-08-01

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

  9. Limited human epidermal growth factor receptor 2 discordance in metastatic breast cancer patients treated with trastuzumab, a population based study

    NARCIS (Netherlands)

    van Rooijen, J.M.; de Munck, L.; de Graaf, J.C.; Siesling, Sabine; de Vries, Erik G.; Boers, J.E.

    2014-01-01

    Background Accurate assessment of the human epidermal growth factor receptor 2 (HER2) in breast cancer is essential for proper treatment decisions. HER2 positivity confirmation rates in breast cancer trials by central testing pathology laboratories were reported to be approximately 85%. The aim of

  10. Limited human epidermal growth factor receptor 2 discordance in metastatic breast cancer patients treated with trastuzumab, a population based study

    NARCIS (Netherlands)

    van Rooijen, J. M.; de Munck, L.; de Graaf, J. C.; Siesling, S.; de Vries, E. G.; Boers, J. E.

    Background: Accurate assessment of the human epidermal growth factor receptor 2 (HER2) in breast cancer is essential for proper treatment decisions. HER2 positivity confirmation rates in breast cancer trials by central testing pathology laboratories were reported to be approximately 85%. The aim of

  11. Identification of EPSTI1, a novel gene induced by epithelial-stromal interaction in human breast cancer

    DEFF Research Database (Denmark)

    Nielsen, Helga Lind; Rønnov-Jessen, Lone; Villadsen, René

    2002-01-01

    reading frame (ORF) encoding a putative 307-amino-acid protein, and mapped to chromosome 13q13.3. EPSTI1 was highly upregulated in invasive breast carcinomas compared with normal breast. In a tissue mRNA panel the most prominent expression of EPSTI1 was found in placenta. Thus, EPSTI1 is a novel human...

  12. Sulforaphane causes epigenetic repression of hTERT expression in human breast cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Syed M Meeran

    Full Text Available BACKGROUND: Sulforaphane (SFN, an isothiocyanate found in cruciferous vegetables, is a common dietary component that has histone deacetylase inhibition activity and exciting potential in cancer prevention. The mechanisms by which SFN imparts its chemopreventive properties are of considerable interest and little is known of its preventive potential for breast cancer. PRINCIPAL FINDINGS: We found that SFN significantly inhibits the viability and proliferation of breast cancer cells in vitro while it has negligible effects on normal breast cells. Inhibition of telomerase has received considerable attention because of its high expression in cancer cells and extremely low level of expression in normal cells. SFN treatment dose- and time-dependently inhibited human telomerase reverse transcriptase (hTERT, the catalytic regulatory subunit of telomerase, in both MCF-7 and MDA-MB-231 human breast cancer cells. DNA methyltransferases (DNMTs, especially DNMT1 and DNMT3a, were also decreased in SFN-treated breast cancer cells suggesting that SFN may repress hTERT by impacting epigenetic pathways. Down-regulation of DNMTs in response to SFN induced site-specific CpG demethylation occurring primarily in the first exon of the hTERT gene thereby facilitating CTCF binding associated with hTERT repression. Chromatin immunoprecipitation (ChIP analysis of the hTERT promoter revealed that SFN increased the level of active chromatin markers acetyl-H3, acetyl-H3K9 and acetyl-H4, whereas the trimethyl-H3K9 and trimethyl-H3K27 inactive chromatin markers were decreased in a dose-dependent manner. SFN-induced hyperacetylation facilitated the binding of many hTERT repressor proteins such as MAD1 and CTCF to the hTERT regulatory region. Depletion of CTCF using siRNA reduced the SFN-induced down-regulation of hTERT mRNA transcription in these breast cancer cells. In addition, down-regulation of hTERT expression facilitated the induction of cellular apoptosis in human breast

  13. Critical role of c-Jun overexpression in liver metastasis of human breast cancer xenograft model

    International Nuclear Information System (INIS)

    Zhang, Yan; Hu, Meiru; Shen, Beifen; Guo, Ning; Pu, Xiaoyun; Shi, Ming; Chen, Liyong; Song, Yuhua; Qian, Lu; Yuan, Guogang; Zhang, Hao; Yu, Ming

    2007-01-01

    c-Jun/AP-1 has been linked to invasive properties of aggressive breast cancer. Recently, it has been reported that overexpression of c-Jun in breast cancer cell line MCF-7 resulted in increased AP-1 activity, motility and invasiveness of the cells in vitro and tumor formation in nude mice. However, the role of c-Jun in metastasis of human breast cancer in vivo is currently unknown. To further investigate the direct involvement of c-Jun in tumorigenesis and metastasis, in the present study, the effects of c-Jun overexpression were studied in both in vitro and in nude mice. Ectopic overexpression of c-Jun promoted the growth of MCF-7 cells and resulted in a significant increase in the percentage of cells in S phase and increased motility and invasiveness. Introduction of c-Jun gene alone into weakly invasive MCF-7 cells resulted in the transfected cells capable of metastasizing to the nude mouse liver following tail vein injection. The present study confirms that overexpression of c-Jun contributes to a more invasive phenotype in MCF-7 cells. It indicates an interesting relationship between c-Jun expression and increased property of adhesion, migration and in vivo liver metastasis of MCF-7/c-Jun cells. The results provide further evidence that c-Jun is involved in the metastasis of breast cancer. The finding also opens an opportunity for development of anti-c-Jun strategies in breast cancer therapy

  14. The investigation of lactalbumin as a possible marker for human breast cancer

    International Nuclear Information System (INIS)

    Woods, K.L.; Cove, D.H.; Morrison, J.M.; Heath, D.A.

    1979-01-01

    Measurable amounts of the whey protein lactalbumin have been found in the cytosol of over a third of 89 primary breast cancers using a specific radioimmunoassay. With a modification of the method which prevents interference from endogenous antibodies, serum levels of lactalbumin have been measured in 83 subjects with breast cancer, 45 subjects with benign mammary dysplasic and 63 controls. In earlier studies of normal women, we found that circulating lactalbumin was not found in subjects aged over 45 yr but was commonly present below that age since the patients with benign dysplasia had a mean age of 35.0 yr and the breast carcinoma patients a mean age of 60.4 yr, separate control groups were necessary for the two patient groups. Circulating lactalbumin was found in 12% of patients with operable breast cancer, 24% of patients with metastatic disease and in none of the age-matched controls circulating lactalbumin was detected no more often in the patients with benign dysplasia than in corresponding controls. It appears that a sizeable minority of human breast carcinomas are able to synthesise lactalbumin in sufficient quantity to produce a measurable level in the blood. (author)

  15. The neurotensin receptor-1 pathway contributes to human ductal breast cancer progression.

    Directory of Open Access Journals (Sweden)

    Sandra Dupouy

    Full Text Available BACKGROUND: The neurotensin (NTS and its specific high affinity G protein coupled receptor, the NT1 receptor (NTSR1, are considered to be a good candidate for one of the factors implicated in neoplastic progression. In breast cancer cells, functionally expressed NT1 receptor coordinates a series of transforming functions including cellular migration and invasion. METHODS AND RESULTS: we investigated the expression of NTS and NTSR1 in normal human breast tissue and in invasive ductal breast carcinomas (IDCs by immunohistochemistry and RT-PCR. NTS is expressed and up-regulated by estrogen in normal epithelial breast cells. NTS is also found expressed in the ductal and invasive components of IDCs. The high expression of NTSR1 is associated with the SBR grade, the size of the tumor, and the number of metastatic lymph nodes. Furthermore, the NTSR1 high expression is an independent factor of prognosis associated with the death of patients. CONCLUSION: these data support the activation of neurotensinergic deleterious pathways in breast cancer progression.

  16. Involvement of macrophage migration inhibitory factor and its receptor (CD74) in human breast cancer.

    Science.gov (United States)

    Richard, Vincent; Kindt, Nadège; Decaestecker, Christine; Gabius, Hans-Joachim; Laurent, Guy; Noël, Jean-Christophe; Saussez, Sven

    2014-08-01

    Macrophage migration inhibitory factor (MIF) and its receptor CD74 appear to be involved in tumorigenesis. We evaluated, by immunohistochemical staining, the tissue expression and distribution of MIF and CD74 in serial sections of human invasive breast cancer tumor specimens. The serum MIF level was also determined in breast cancer patients. We showed a significant increase in serum MIF average levels in breast cancer patients compared to healthy individuals. MIF tissue expression, quantified by a modified Allred score, was strongly increased in carcinoma compared to tumor-free specimens, in the cancer cells and in the peritumoral stroma, with fibroblasts the most intensely stained. We did not find any significant correlation with histoprognostic factors, except for a significant inverse correlation between tumor size and MIF stromal positivity. CD74 staining was heterogeneous and significantly decreased in cancer cells but increased in the surrounding stroma, namely in lymphocytes, macrophages and vessel endothelium. There was no significant variation according to classical histoprognostic factors, except that CD74 stromal expression was significantly correlated with triple-negative receptor (TRN) status and the absence of estrogen receptors. In conclusion, our data support the concept of a functional role of MIF in human breast cancer. In addition to auto- and paracrine effects on cancer cells, MIF could contribute to shape the tumor microenvironment leading to immunomodulation and angiogenesis. Interfering with MIF effects in breast tumors in a therapeutic perspective remains an attractive but complex challenge. Level of co-expression of MIF and CD74 could be a surrogate marker for efficacy of anti-angiogenic drugs, particularly in TRN breast cancer tumor.

  17. Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells

    International Nuclear Information System (INIS)

    Weng, Yu-I; Hsu, Pei-Yin; Liyanarachchi, Sandya; Liu, Joseph; Deatherage, Daniel E.; Huang Yiwen; Zuo Tao; Rodriguez, Benjamin; Lin, Ching-Hung; Cheng, Ann-Lii; Huang, Tim H.-M.

    2010-01-01

    Substantial evidence indicates that exposure to bisphenol A (BPA) during early development may increase breast cancer risk later in life. The changes may persist into puberty and adulthood, suggesting an epigenetic process being imposed in differentiated breast epithelial cells. The molecular mechanisms by which early memory of BPA exposure is imprinted in breast progenitor cells and then passed onto their epithelial progeny are not well understood. The aim of this study was to examine epigenetic changes in breast epithelial cells treated with low-dose BPA. We also investigated the effect of BPA on the ERα signaling pathway and global gene expression profiles. Compared to control cells, nuclear internalization of ERα was observed in epithelial cells preexposed to BPA. We identified 170 genes with similar expression changes in response to BPA. Functional analysis confirms that gene suppression was mediated in part through an ERα-dependent pathway. As a result of exposure to BPA or other estrogen-like chemicals, the expression of lysosomal-associated membrane protein 3 (LAMP3) became epigenetically silenced in breast epithelial cells. Furthermore, increased DNA methylation in the LAMP3 CpG island was this repressive mark preferentially occurred in ERα-positive breast tumors. These results suggest that the in vitro system developed in our laboratory is a valuable tool for exposure studies of BPA and other xenoestrogens in human cells. Individual and geographical differences may contribute to altered patterns of gene expression and DNA methylation in susceptible loci. Combination of our exposure model with epigenetic analysis and other biochemical assays can give insight into the heritable effect of low-dose BPA in human cells.

  18. Breast carcinoma cells modulate the chemoattractive activity of human bone marrow-derived mesenchymal stromal cells by interfering with CXCL12.

    Science.gov (United States)

    Wobus, Manja; List, Catrin; Dittrich, Tobias; Dhawan, Abhishek; Duryagina, Regina; Arabanian, Laleh S; Kast, Karin; Wimberger, Pauline; Stiehler, Maik; Hofbauer, Lorenz C; Jakob, Franz; Ehninger, Gerhard; Anastassiadis, Konstantinos; Bornhäuser, Martin

    2015-01-01

    We investigated whether breast tumor cells can modulate the function of mesenchymal stromal cells (MSCs) with a special emphasis on their chemoattractive activity towards hematopoietic stem and progenitor cells (HSPCs). Primary MSCs as well as a MSC line (SCP-1) were cocultured with primary breast cancer cells, MCF-7, MDA-MB231 breast carcinoma or MCF-10A non-malignant breast epithelial cells or their conditioned medium. In addition, the frequency of circulating clonogenic hematopoietic progenitors was determined in 78 patients with breast cancer and compared with healthy controls. Gene expression analysis of SCP-1 cells cultured with MCF-7 medium revealed CXCL12 (SDF-1) as one of the most significantly downregulated genes. Supernatant from both MCF-7 and MDA-MB231 reduced the CXCL12 promoter activity in SCP-1 cells to 77% and 47%, respectively. Moreover, the CXCL12 mRNA and protein levels were significantly reduced. As functional consequence of lower CXCL12 levels, we detected a decreased trans-well migration of HSPCs towards MSC/tumor cell cocultures or conditioned medium. The specificity of this effect was confirmed by blocking studies with the CXCR4 antagonist AMD3100. Downregulation of SP1 and increased miR-23a levels in MSCs after contact with tumor cell medium as well as enhanced TGFβ1 expression were identified as potential molecular regulators of CXCL12 activity in MSCs. Moreover, we observed a significantly higher frequency of circulating colony-forming hematopoietic progenitors in patients with breast cancer compared with healthy controls. Our in vitro results propose a potential new mechanism by which disseminated tumor cells in the bone marrow may interfere with hematopoiesis by modulating CXCL12 in protected niches. © 2014 UICC.

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

    International Nuclear Information System (INIS)

    Samoszuk, Michael; Tan, Jenny; Chorn, Guillaume

    2005-01-01

    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

  20. Anti-angiogenic activity in metastasis of human breast cancer cells irradiated by a proton beam

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyu-Shik; Shin, Jin-Sun; Nam, Kyung-Soo [Dongguk University, Gyeongju (Korea, Republic of); Shon, Yun-Hee [Kyungpook National University Hospital, Daegu (Korea, Republic of)

    2012-07-15

    Angiogenesis is an essential process of metastasis in human breast cancer. We investigated the effects of proton beam irradiation on angiogenic enzyme activities and their expressions in MCF-7 human breast cancer cells. The regulation of angiogenic regulating factors, of transforming growth factor-β (TGF-β) and of vesicular endothelial growth factor (VEGF) expression in breast cancer cells irradiated with a proton beam was studied. Aromatase activity and mRNA expression, which is correlated with metastasis, were significantly decreased by irradiation with a proton beam in a dose-dependent manner. TGF-β and VEGF transcriptions were also diminished by proton beam irradiation. In contrast, transcription of tissue inhibitors of matrix metalloproteinases (TIMPs), also known as biological inhibitors of matrix metalloproteinases (MMPs), was dose-dependently enhanced. Furthermore, an increase in the expression of TIMPs caused the MMP-9 activity to be diminished and the MMP-9 and the MMP-2 expressions to be decreased. These results suggest that inhibition of angiogenesis by proton beam irradiation in breast cancer cells is closely related to inhibitions of aromatase activity and transcription and to down-regulation of TGF-β and VEGF transcription.

  1. The plasticity of human breast carcinoma cells is more than epithelial to mesenchymal conversion

    International Nuclear Information System (INIS)

    William Petersen, Ole; Lind Nielsen, Helga; Gudjonsson, Thorarinn; Villadsen, René; Rønnov-Jessen, Lone; Bissell, Mina J

    2001-01-01

    The human breast comprises three lineages: the luminal epithelial lineage, the myoepithelial lineage, and the mesenchymal lineage. It has been widely accepted that human breast neoplasia pertains only to the luminal epithelial lineage. In recent years, however, evidence has accumulated that neoplastic breast epithelial cells may be substantially more plastic in their differentiation repertoire than previously anticipated. Thus, along with an increasing availability of markers for the myoepithelial lineage, at least a partial differentiation towards this lineage is being revealed frequently. It has also become clear that conversions towards the mesenchymal lineage actually occur, referred to as epithelial to mesenchymal transitions. Indeed, some of the so-called myofibroblasts surrounding the tumor may have an epithelial origin rather than a mesenchymal origin. Because myoepithelial cells, epithelial to mesenchymal transition-derived cells, genuine stromal cells and myofibroblasts share common markers, we now need to define a more ambitious set of markers to distinguish these cell types in the microenvironment of the tumors. This is necessary because the different microenvironments may confer different clinical outcomes. The aim of this commentary is to describe some of the inherent complexities in defining cellular phenotypes in the microenvironment of breast cancer and to expand wherever possible on the implications for tumor suppression and progression

  2. Expression of oncogen c-erbB-2 (neu/HER-2) in human breast cancer

    International Nuclear Information System (INIS)

    Michelin, Severino C.; Mayo, Jose

    2000-01-01

    Breast cancer continues to be one of the leading causes of death from cancer among women and represents the most serious challenge to therapeutic control. Amplification and overexpression of the c-erbB-2 proto-oncogene occurs in as many as 30 % of all breast cancers and has been correlated with lymph node metastasis and poor prognosis in breast cancer patients. This gene know as neu, HER-2 or c-erbB-2 in among those most frequently altered in human cancer. It was first identified as a transforming gene activated in chemically induced rat neuroectodermal tumors. Early critical studies linked changes in erbB-2 expression and gene copy number to several human cancer, notably breast, ovarian and gastric cancer. Owing to its accessible location at the cell surface, erbB-2 is now under intensive scrutiny as a therapeutic target. In this review we will summarize the involvement of the c-erbB-2 gene in tumorigenesis. (author)

  3. The plasticity of human breast carcinoma cells is more than epithelial to mesenchymal conversion

    Energy Technology Data Exchange (ETDEWEB)

    Petersen, Ole William; Nielsen, Helga Lind; Gudjonsson, Thorarinn; Villadsen, Ren& #233; ; Ronnov-Jessen, Lone; Bissell, Mina J.

    2001-05-12

    The human breast comprises three lineages: the luminal epithelial lineage, the myoepithelial lineage, and the mesenchymal lineage. It has been widely accepted that human breast neoplasia pertains only to the luminal epithelial lineage. In recent years, however, evidence has accumulated that neoplastic breast epithelial cells may be substantially more plastic in their differentiation repertoire than previously anticipated. Thus, along with an increasing availability of markers for the myoepithelial lineage, at least a partial differentiation towards this lineage is being revealed frequently. It has also become clear that conversions towards the mesenchymal lineage actually occur, referred to as epithelial to mesenchymal transitions. Indeed, some of the so-called myofibroblasts surrounding the tumor may indeed have an epithelial origin rather than a mesenchymal origin. Because myoepithelial cells, epithelial to mesenchymal transition-derived cells, genuine stromal cells and myofibroblasts share common markers, we now need to define a more ambitious set of markers to distinguish these cell types in the microenvironment of the tumors. This is necessary because the different microenvironments may confer different clinical outcomes. The aim of this commentary is to describe some of the inherent complexities in defining cellular phenotypes in the microenvironment of breast cancer and to expand wherever possible on the implications for tumor suppression and progression.

  4. Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

    Energy Technology Data Exchange (ETDEWEB)

    Erez, Neta, E-mail: netaerez@post.tau.ac.il [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Glanz, Sarah [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Raz, Yael [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Department of Obstetrics and Gynecology, LIS Maternity Hospital, Tel Aviv Sourasky Medical Center, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Avivi, Camilla [Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Barshack, Iris [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel)

    2013-08-02

    Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- Abstract: Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.

  5. Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

    International Nuclear Information System (INIS)

    Erez, Neta; Glanz, Sarah; Raz, Yael; Avivi, Camilla; Barshack, Iris

    2013-01-01

    Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- Abstract: Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics

  6. Prevalence and factors associated with breast milk donation in banks that receive human milk in primary health care units

    Directory of Open Access Journals (Sweden)

    Tatiana Mota Xavier de Meneses

    2017-07-01

    Conclusions: Encouragement to breast milk donation, and information and help provided by primary health care unit professionals to breastfeeding were shown to be important for the practice of human milk donation.

  7. Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in infants three months of age

    DEFF Research Database (Denmark)

    Main, Katharina M; Mortensen, Gerda Krog; Kaleva, Marko M

    2006-01-01

    Phthalates adversely affect the male reproductive system in animals. We investigated whether phthalate monoester contamination of human breast milk had any influence on the postnatal surge of reproductive hormones in newborn boys as a sign of testicular dysgenesis....

  8. Induction of human breast cell carcinogenesis by triclocarban and intervention by curcumin

    Energy Technology Data Exchange (ETDEWEB)

    Sood, Shilpa; Choudhary, Shambhunath; Wang, Hwa-Chain Robert, E-mail: hcrwang@utk.edu

    2013-09-06

    Highlights: •Triclocarban exposure induces breast epithelial cell carcinogenesis. •Triclocarban induces the Erk–Nox pathway, ROS elevation, and DNA damage. •Physiological doses of triclocarban induce cellular carcinogenesis. •Non-cytotoxic curcumin blocks triclocarban-induced carcinogenesis and pathways. -- Abstract: More than 85% of breast cancers are sporadic and attributable to long-term exposure to environmental carcinogens and co-carcinogens. To identify co-carcinogens with abilities to induce cellular pre-malignancy, we studied the activity of triclocarban (TCC), an antimicrobial agent commonly used in household and personal care products. Here, we demonstrated, for the first time, that chronic exposure to TCC at physiologically-achievable nanomolar concentrations resulted in progressive carcinogenesis of human breast cells from non-cancerous to pre-malignant. Pre-malignant carcinogenesis was measured by increasingly-acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth and increased cell proliferation, without acquisition of cellular tumorigenicity. Long-term TCC exposure also induced constitutive activation of the Erk–Nox pathway and increases of reactive oxygen species (ROS) in cells. A single TCC exposure induced transient induction of the Erk–Nox pathway, ROS elevation, increased cell proliferation, and DNA damage in not only non-cancerous breast cells but also breast cancer cells. Using these constitutively- and transiently-induced changes as endpoints, we revealed that non-cytotoxic curcumin was effective in intervention of TCC-induced cellular pre-malignancy. Our results lead us to suggest that the co-carcinogenic potential of TCC should be seriously considered in epidemiological studies to reveal the significance of TCC in the development of sporadic breast cancer. Using TCC-induced transient and constitutive endpoints as targets will likely help identify non-cytotoxic preventive

  9. Expression of melatonin receptor MT1 in cells of human invasive ductal breast carcinoma.

    Science.gov (United States)

    Jablonska, Karolina; Pula, Bartosz; Zemla, Agata; Owczarek, Tomasz; Wojnar, Andrzej; Rys, Janusz; Ambicka, Aleksandra; Podhorska-Okolow, Marzena; Ugorski, Maciej; Dziegiel, Piotr

    2013-04-01

    In humans, two main types of membrane melatonin receptors have been identified, MT1 and MT2. Expression of MT1 in neoplastic cells seems to increase the efficacy of melatonin's oncostatic activity. The purpose of this study was to determine the distribution and the intensity of MT1 expression in breast cancer cells and to correlate it with clinicopathological factors. Immunohistochemical studies (IHC) were conducted on 190 cases of invasive ductal breast carcinomas (IDC) and molecular studies were performed on 29 cases of frozen tumor fragments and selected breast cancer cell lines. Most of the studied tumors manifested a membranous/cytoplasmic IHC expression of MT1. In IDC, the MT1 expression was higher than in fibrocystic breast disease. MT1 expression was higher in estrogen receptor positive (ER+) and HER2 positive (HER2+) tumors. Triple negative tumors (TN) manifested the lowest MT1 expression level. The lowest MT1 protein expression level was noted in the TN breast cancer cell line MDA-MB-231 compared with ER+ cell lines MCF-7 and SK-BR-3. MT1 mRNA expression was negatively correlated with the malignancy grade of the studied IDC cases. Moreover, higher MT1 expression was associated with patients' longer overall survival (OS) in the group of ER+ breast cancers and treated with tamoxifen. Multivariate analysis indicated that MT1 was an independent prognostic factor in the ER+ tumors for OS and event-free survival in the ER+ tumors. The results of this study may point to a potential prognostic and therapeutic significance of MT1 in IDC. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  10. Targeting ceramide metabolic pathway induces apoptosis in human breast cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Vethakanraj, Helen Shiphrah; Babu, Thabraz Ahmed; Sudarsanan, Ganesh Babu; Duraisamy, Prabhu Kumar; Ashok Kumar, Sekar, E-mail: sekarashok@gmail.com

    2015-08-28

    The sphingolipid ceramide is a pro apoptotic molecule of ceramide metabolic pathway and is hydrolyzed to proliferative metabolite, sphingosine 1 phosphate by the action of acid ceramidase. Being upregulated in the tumors of breast, acid ceramidase acts as a potential target for breast cancer therapy. We aimed at targeting this enzyme with a small molecule acid ceramidase inhibitor, Ceranib 2 in human breast cancer cell lines MCF 7 and MDA MB 231. Ceranib 2 effectively inhibited the growth of both the cell lines in dose and time dependant manner. Morphological apoptotic hallmarks such as chromatin condensation, fragmented chromatin were observed in AO/EtBr staining. Moreover, ladder pattern of fragmented DNA observed in DNA gel electrophoresis proved the apoptotic activity of Ceranib 2 in breast cancer cell lines. The apoptotic events were associated with significant increase in the expression of pro-apoptotic genes (Bad, Bax and Bid) and down regulation of anti-apoptotic gene (Bcl 2). Interestingly, increase in sub G1 population of cell cycle phase analysis and elevated Annexin V positive cells after Ceranib 2 treatment substantiated its apoptotic activity in MCF 7 and MDA MB 231 cell lines. Thus, we report Ceranib 2 as a potent therapeutic agent against both ER{sup +} and ER{sup −} breast cancer cell lines. - Highlights: • Acid Ceramidase inhibitor, Ceranib 2 induced apoptosis in Breast cancer cell lines (MCF 7 and MDA MB 231 cell lines). • Apoptosis is mediated by DNA fragmentation and cell cycle arrest. • Ceranib 2 upregulated the expression of pro-apoptotic genes and down regulated anti-apoptotic gene expression. • More potent compared to the standard drug Tamoxifen.

  11. Targeting ceramide metabolic pathway induces apoptosis in human breast cancer cell lines

    International Nuclear Information System (INIS)

    Vethakanraj, Helen Shiphrah; Babu, Thabraz Ahmed; Sudarsanan, Ganesh Babu; Duraisamy, Prabhu Kumar; Ashok Kumar, Sekar

    2015-01-01

    The sphingolipid ceramide is a pro apoptotic molecule of ceramide metabolic pathway and is hydrolyzed to proliferative metabolite, sphingosine 1 phosphate by the action of acid ceramidase. Being upregulated in the tumors of breast, acid ceramidase acts as a potential target for breast cancer therapy. We aimed at targeting this enzyme with a small molecule acid ceramidase inhibitor, Ceranib 2 in human breast cancer cell lines MCF 7 and MDA MB 231. Ceranib 2 effectively inhibited the growth of both the cell lines in dose and time dependant manner. Morphological apoptotic hallmarks such as chromatin condensation, fragmented chromatin were observed in AO/EtBr staining. Moreover, ladder pattern of fragmented DNA observed in DNA gel electrophoresis proved the apoptotic activity of Ceranib 2 in breast cancer cell lines. The apoptotic events were associated with significant increase in the expression of pro-apoptotic genes (Bad, Bax and Bid) and down regulation of anti-apoptotic gene (Bcl 2). Interestingly, increase in sub G1 population of cell cycle phase analysis and elevated Annexin V positive cells after Ceranib 2 treatment substantiated its apoptotic activity in MCF 7 and MDA MB 231 cell lines. Thus, we report Ceranib 2 as a potent therapeutic agent against both ER + and ER − breast cancer cell lines. - Highlights: • Acid Ceramidase inhibitor, Ceranib 2 induced apoptosis in Breast cancer cell lines (MCF 7 and MDA MB 231 cell lines). • Apoptosis is mediated by DNA fragmentation and cell cycle arrest. • Ceranib 2 upregulated the expression of pro-apoptotic genes and down regulated anti-apoptotic gene expression. • More potent compared to the standard drug Tamoxifen

  12. Energy intake from human milk covers the requirement of 6-month-old Senegalese exclusively breast-fed infants

    International Nuclear Information System (INIS)

    Agne-Djigo, Anta; Kwadjode, Komlan M.; Idohou-Dossou, Nicole; Diouf, Adama; Guiro, Amadou T.; Wade, Salimata

    2013-01-01

    Exclusive breast-feeding until 6 months is advised by the WHO as the best practice to feed infants. Yet, some studies have suggested a gap between energy requirements and the energy provided by human milk for many infants at 6 months. In order to assess the adequacy of WHO recommendations in 6-month-old Senegalese lactating infants, a comprehensive study was designed to measure human milk intake by the dose-to-the mother 2H2O turnover method. Infants energy intakes were calculated using daily breast milk intake and the energy content of milk was estimated on the basis of creamatocrit. Of the fifty-nine mother-infant pairs enrolled, fifteen infants were exclusively breast-fed (Ex) while forty-four were partially breast-fed Infants breast milk intake was significantly higher in the Ex group (993 (SD 135)g/d, n 15) compared with the Part group (828 (SD 222)g/d, n 44, P= 0.009). Breast milk energy content as well as infants growth was comparable in both groups. However, infants' energy intake from human milk was significantly higher (364 (SD 50)kJ/kg per d (2586 (SD 448)kJ/d)) in the Ex group than in the Part group (289 (SD 66)kJ/kg per d (2150 (SD 552)kJ/d), P<0.01). Compared with WHO recommendations, the results demonstrate that energy intake from breast milk was low in partially breast-fed infants while exclusively breast-fed 6-month-old Senegalese infants received adequate energy from human milk alone, the most complete food for infants. Therefore, advocacy of exclusive breast-feeding until 6 months should be strengthened.

  13. Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in infants three months of age

    DEFF Research Database (Denmark)

    Main, Katharina M; Mortensen, Gerda Krog; Kaleva, Marko M

    2006-01-01

    Phthalates adversely affect the male reproductive system in animals. We investigated whether phthalate monoester contamination of human breast milk had any influence on the postnatal surge of reproductive hormones in newborn boys as a sign of testicular dysgenesis.......Phthalates adversely affect the male reproductive system in animals. We investigated whether phthalate monoester contamination of human breast milk had any influence on the postnatal surge of reproductive hormones in newborn boys as a sign of testicular dysgenesis....

  14. A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Chun, Sung Kook [Department of Brain & Cognitive Sciences, Daegu-Gyeongbuk Institute of Science & Technology, Daegu, 711-873 (Korea, Republic of); Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Chung, Sooyoung [Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705 (Korea, Republic of); Kim, Hee-Dae [Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Lee, Ju Hyung [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of); Jang, Jaebong [College of Pharmacy, Seoul National University, Seoul, 151-742 (Korea, Republic of); Kim, Jeongah; Kim, Doyeon [Department of Brain & Cognitive Sciences, Daegu-Gyeongbuk Institute of Science & Technology, Daegu, 711-873 (Korea, Republic of); Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Son, Gi Hoon [Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705 (Korea, Republic of); Oh, Young J. [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of); Suh, Young-Ger [College of Pharmacy, Seoul National University, Seoul, 151-742 (Korea, Republic of); Lee, Cheol Soon [Gachon Clinical Trials Center, Gachon University, Incheon, 417-842 (Korea, Republic of); and others

    2015-11-13

    Disruption of circadian rhythm is a major cause of breast cancer in humans. Cryptochrome (CRY), a circadian transcription factor, is a risk factor for initiation of breast cancer, and it is differentially expressed between normal and breast cancer tissues. Here, we evaluated the anti-proliferative and pro-apoptotic activity of KS15, a recently discovered small-molecule inhibitor of CRY, in human breast cancer cells. First, we investigated whether KS15 treatment could promote E-box-mediated transcription by inhibiting the activity of CRY in MCF-7 human breast cancer cells. Protein and mRNA levels of regulators of cell cycle and apoptosis, as well as core clock genes, were differentially modulated in response to KS15. Next, we investigated whether KS15 could inhibit proliferation and increase sensitivity to anti-tumor drugs in MCF-7 cells. We found that KS15 decreased the speed of cell growth and increased the chemosensitivity of MCF-7 cells to doxorubicin and tamoxifen, but had no effect on MCF-10A cells. These findings suggested that pharmacological inhibition of CRY by KS15 exerts an anti-proliferative effect and increases sensitivity to anti-tumor drugs in a specific type of breast cancer. - Highlights: • Cryptochrome inhibitor (KS15) has anti-tumor activity to human breast cancer cells. • KS15 induces differential changes in cell cycle regulators and pro-apoptotic genes. • KS15 inhibits MCF-7 cell growth and enhances susceptibility to anti-tumor drugs.

  15. A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells

    International Nuclear Information System (INIS)

    Chun, Sung Kook; Chung, Sooyoung; Kim, Hee-Dae; Lee, Ju Hyung; Jang, Jaebong; Kim, Jeongah; Kim, Doyeon; Son, Gi Hoon; Oh, Young J.; Suh, Young-Ger; Lee, Cheol Soon

    2015-01-01

    Disruption of circadian rhythm is a major cause of breast cancer in humans. Cryptochrome (CRY), a circadian transcription factor, is a risk factor for initiation of breast cancer, and it is differentially expressed between normal and breast cancer tissues. Here, we evaluated the anti-proliferative and pro-apoptotic activity of KS15, a recently discovered small-molecule inhibitor of CRY, in human breast cancer cells. First, we investigated whether KS15 treatment could promote E-box-mediated transcription by inhibiting the activity of CRY in MCF-7 human breast cancer cells. Protein and mRNA levels of regulators of cell cycle and apoptosis, as well as core clock genes, were differentially modulated in response to KS15. Next, we investigated whether KS15 could inhibit proliferation and increase sensitivity to anti-tumor drugs in MCF-7 cells. We found that KS15 decreased the speed of cell growth and increased the chemosensitivity of MCF-7 cells to doxorubicin and tamoxifen, but had no effect on MCF-10A cells. These findings suggested that pharmacological inhibition of CRY by KS15 exerts an anti-proliferative effect and increases sensitivity to anti-tumor drugs in a specific type of breast cancer. - Highlights: • Cryptochrome inhibitor (KS15) has anti-tumor activity to human breast cancer cells. • KS15 induces differential changes in cell cycle regulators and pro-apoptotic genes. • KS15 inhibits MCF-7 cell growth and enhances susceptibility to anti-tumor drugs.

  16. Effect of aluminium on migratory and invasive properties of MCF-7 human breast cancer cells in culture.

    Science.gov (United States)

    Darbre, Philippa D; Bakir, Ayse; Iskakova, Elzira

    2013-11-01

    Aluminium (Al) has been measured in human breast tissue, nipple aspirate fluid and breast cyst fluid, and recent studies have shown that at tissue concentrations, aluminium can induce DNA damage and suspension growth in human breast epithelial cells. This paper demonstrates for the first time that exposure to aluminium can also increase migratory and invasive properties of MCF-7 human breast cancer cells. Long-term (32 weeks) but not short-term (1 week) exposure of MCF-7 cells to 10(-4) M aluminium chloride or 10(-4) M aluminium chlorohydrate increased motility of the cells as measured by live cell imaging (cumulative length moved by individual cells), by a wound healing assay and by migration in real time through 8 μm pores of a membrane using xCELLigence technology. Long-term exposure (37 weeks) to 10(-4) M aluminium chloride or 10(-4) M aluminium chlorohydrate also increased the ability of MCF-7 cells to invade through a matrigel layer as measured in real time using the xCELLigence system. Although molecular mechanisms remain to be characterized, the ability of aluminium salts to increase migratory and invasive properties of MCF-7 cells suggests that the presence of aluminium in the human breast could influence metastatic processes. This is important because mortality from breast cancer arises mainly from tumour spread rather than from the presence of a primary tumour in the breast. © 2013.

  17. Identification of Genetic Markers of the Invasive Phenotype in Human Breast Cancer

    Science.gov (United States)

    2000-10-01

    Although it is interesting that the nature of this correlation chemistry are necessary to confirm this observation, the is different between the in...Bastholm L, Elling F, chemistry protocol, which may effect staining with some Georgiev G, Lukanidin E: Effect of mtsl ($100A4) expression on the...Mandinova A, Atar D, Schafer BW, Spiess M, Aebi U, Heizmann CW: J, Schnitt S, Livingston DM: Location of BRCA1 in human breast and Distinct

  18. Re-evaluation of the prolactin receptor expression in human breast cancer

    DEFF Research Database (Denmark)

    Galsgaard, Elisabeth Douglas; Rasmussen, Birgitte Bruun; Folkesson, Charlotta Grånäs

    2009-01-01

    , we evaluated the specificity of commercially available anti-human PRLR antibodies (B6.2, U5, PRLRi pAb, 1A2B1, 250448 and H-300). The latter three antibodies were found to specifically recognise PRLR. The relative PRLR expression level detected with these antibodies closely reflected the level...... to be sufficient to mediate PRL responsiveness in breast cancer cell lines....

  19. Methylation of PLCD1 and adenovirus-mediated PLCD1 overexpression elicits a gene therapy effect on human breast cancer

    International Nuclear Information System (INIS)

    Mu, Haixi; Wang, Na; Zhao, Lijuan; Li, Shuman; Li, Qianqian; Chen, Ling; Luo, Xinrong; Qiu, Zhu; Li, Lili; Ren, Guosheng; Xu, Yongzhu; Zhou, Xiangyang; Xiang, Tingxiu

    2015-01-01

    Our previous study showed that PLCD1 significantly decreases cell proliferation and affects cell cycle progression in breast cancer cells. In the present study, we aimed to investigate its functional and molecular mechanisms, and whether or not can become a new target for gene therapies. We found reduced PLCD1 protein expression in breast tumor tissues compared with paired surgical margin tissues. PLCD1 promoter CpG methylation was detected in 55 of 96 (57%) primary breast tumors, but not in surgical-margin tissues and normal breast tissues. Ectopic expression of PLCD1 inhibited breast tumor cell proliferation in vivo by inducing apoptosis and suppressed tumor cell migration by regulating cytoskeletal reorganization proteins including RhoA and phospho-cofilin. Furthermore, we found that PLCD1 induced p53 accumulation, increased p27 and p21 protein levels, and cleaved PARP. Finally, we constructed an adenoviral vector expressing PLCD1 (AdH5-PLCD1), which exhibited strong cytotoxicity in breast cancer cells. Our findings provide insights into the development of PLCD1 gene therapies for breast cancer and perhaps, other human cancers. - Highlights: • PLCD1 is downregulated via hypermethylation in breast cancer. • PLCD1 suppressed cell migration by regulating cytoskeletal reorganization proteins. • Adenovirus AdHu5-PLCD1 may be a novel therapeutic option for breast cancer

  20. Methylation of PLCD1 and adenovirus-mediated PLCD1 overexpression elicits a gene therapy effect on human breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mu, Haixi [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Department of Endocrine and breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Wang, Na; Zhao, Lijuan; Li, Shuman; Li, Qianqian; Chen, Ling; Luo, Xinrong; Qiu, Zhu [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Li, Lili [Cancer Epigenetics Laboratory, Department of Clinical Oncology, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong and CUHK Shenzhen Research Institute (Hong Kong); Ren, Guosheng [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Department of Endocrine and breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Xu, Yongzhu [Chongqing Health Service Center, Chongqing 400020 (China); Zhou, Xiangyang [The Wistar Institute, Philadelphia, PA (United States); Xiang, Tingxiu, E-mail: xiangtx1@gmail.com [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China)

    2015-03-15

    Our previous study showed that PLCD1 significantly decreases cell proliferation and affects cell cycle progression in breast cancer cells. In the present study, we aimed to investigate its functional and molecular mechanisms, and whether or not can become a new target for gene therapies. We found reduced PLCD1 protein expression in breast tumor tissues compared with paired surgical margin tissues. PLCD1 promoter CpG methylation was detected in 55 of 96 (57%) primary breast tumors, but not in surgical-margin tissues and normal breast tissues. Ectopic expression of PLCD1 inhibited breast tumor cell proliferation in vivo by inducing apoptosis and suppressed tumor cell migration by regulating cytoskeletal reorganization proteins including RhoA and phospho-cofilin. Furthermore, we found that PLCD1 induced p53 accumulation, increased p27 and p21 protein levels, and cleaved PARP. Finally, we constructed an adenoviral vector expressing PLCD1 (AdH5-PLCD1), which exhibited strong cytotoxicity in breast cancer cells. Our findings provide insights into the development of PLCD1 gene therapies for breast cancer and perhaps, other human cancers. - Highlights: • PLCD1 is downregulated via hypermethylation in breast cancer. • PLCD1 suppressed cell migration by regulating cytoskeletal reorganization proteins. • Adenovirus AdHu5-PLCD1 may be a novel therapeutic option for breast cancer.

  1. Aptamer-Assisted Detection of the Altered Expression of Estrogen Receptor Alpha in Human Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Rajesh Ahirwar

    Full Text Available An increase in the expression of estrogen receptors (ER and the expanded population of ER-positive cells are two common phenotypes of breast cancer. Detection of the aberrantly expressed ERα in breast cancer is carried out using ERα-antibodies and radiolabelled ligands to make decisions about cancer treatment and targeted therapy. Capitalizing on the beneficial advantages of aptamer over the conventional antibody or radiolabelled ligand, we have identified a DNA aptamer that selectively binds and facilitates the detection of ERα in human breast cancer tissue sections. The aptamer is identified using the high throughput sequencing assisted SELEX screening. Biophysical characterization confirms the binding and formation of a thermodynamically stable complex between the identified DNA aptamer (ERaptD4 and ERα (Ka = 1.55±0.298×108 M(-1; ΔH = 4.32×104±801.1 cal/mol; ΔS = -108 cal/mol/deg. Interestingly, the specificity measurements suggest that the ERaptD4 internalizes into ERα-positive breast cancer cells in a target-selective manner and localizes specifically in the nuclear region. To harness these characteristics of ERaptD4 for detection of ERα expression in breast cancer samples, we performed the aptamer-assisted histochemical analysis of ERα in tissue samples from breast cancer patients. The results were validated by performing the immunohistochemistry on same samples with an ERα-antibody. We found that the two methods agree strongly in assay output (kappa value = 0.930, p-value <0.05 for strong ERα positive and the ERα negative samples; kappa value = 0.823, p-value <0.05 for the weak/moderate ER+ve samples, n = 20. Further, the aptamer stain the ERα-positive cells in breast tissues without cross-reacting to ERα-deficient fibroblasts, adipocytes, or the inflammatory cells. Our results demonstrate a significant consistency in the aptamer-assisted detection of ERα in strong ERα positive, moderate ERα positive and ERα negative

  2. CLDN6 promotes chemoresistance through GSTP1 in human breast cancer

    Directory of Open Access Journals (Sweden)

    Minlan Yang

    2017-11-01

    cytoplasm, and both the expression and enzyme activity of GSTP1 were regulated by p53. Clinicopathologic analysis revealed that GSTP1 expression was positively associated with CLDN6 in human breast cancer samples. Conclusion High expression of CLDN6 confers chemoresistance on breast cancer which is mediated by GSTP1, the activity of which is regulated by p53. Our findings provide a new insight into mechanisms and strategies to overcome chemoresistance in breast cancer.

  3. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer.

    Science.gov (United States)

    Slamon, D J; Godolphin, W; Jones, L A; Holt, J A; Wong, S G; Keith, D E; Levin, W J; Stuart, S G; Udove, J; Ullrich, A

    1989-05-12

    Carcinoma of the breast and ovary account for one-third of all cancers occurring in women and together are responsible for approximately one-quarter of cancer-related deaths in females. The HER-2/neu proto-oncogene is amplified in 25 to 30 percent of human primary breast cancers and this alteration is associated with disease behavior. In this report, several similarities were found in the biology of HER-2/neu in breast and ovarian cancer, including a similar incidence of amplification, a direct correlation between amplification and over-expression, evidence of tumors in which overexpression occurs without amplification, and the association between gene alteration and clinical outcome. A comprehensive study of the gene and its products (RNA and protein) was simultaneously performed on a large number of both tumor types. This analysis identified several potential shortcomings of the various methods used to evaluate HER-2/neu in these diseases (Southern, Northern, and Western blots, and immunohistochemistry) and provided information regarding considerations that should be addressed when studying a gene or gene product in human tissue. The data presented further support the concept that the HER-2/neu gene may be involved in the pathogenesis of some human cancers.

  4. Assessment of levels of mercury in human breast milk in Obuasi Municipality

    International Nuclear Information System (INIS)

    Asamoah-Antwi, Dinah

    2016-07-01

    This study was conducted to assess the levels of mercury in breast milk and its potential health risk to the breastfed infants in Obuasi Municipality. Forty eight (48) individual breast milk samples were collected from mothers in selected health facilities in Obuasi town and it’s environ. Total mercury concentrations were determined in the breast milk samples using advanced mercury analyser (AMA254 Altec s.r.o, in the Czech Republic). Methylmercury levels were determined using high performance liquid chromatography linked to inductively couple plasma mass spectrometry (HPLC-ICP-MS) with isotope dilution. The mean concentrations of Total Hg and Methyl Hg in the breast milk were 0.4043 and 0.1829 μg/L respectively. Total mercury and methylmercury concentrations ranged from 0.080 to 2.320 μg/L and 0.008 to 0.734 μg/L respectively. The estimated intake obtained in this study was lower than the reference dose established by the US EPA (0.3μg/kg/day). However the hazard quotients evaluated showed that the one month old infants had hazard quotient above the 0.2, therefore indicating that there is a potential risk for such infants and need to be managed. It was also found that (65.3%) of the mothers had no knowledge of the exposure route to mercury and it toxicity to humans. (au)

  5. Organochlorine pesticide residues in human breast milk and placenta in Tohoku, Japan

    Energy Technology Data Exchange (ETDEWEB)

    Nakai, K.; Suzuki, K.; Oka, T.; Sugawara, N.; Ohba, T.; Kameo, S.; Satoh, H. [Environmental Heath Sciences, Tohoku Univ. Graduate School of Medicine, Sendai (Japan); Nakamura, T.; Saitoh, Y. [Miyagi Prefectural Inst. of Piblic Health and Environment (Japan); Okamura, K. [Dept. of Obstetrics, Tohoku Univ. Graduate School of Medicine, Sendai (Japan)

    2004-09-15

    Recently, we have started a birth cohort study to examine the effects of exposure to persistent organochemical pollutants and heavy metals on neurodevelopment in Japanese children, The Tohoku Study of Child Development. In this cohort study, biological samples, including maternal peripheral blood, cord blood, placenta, cord tissue, and breast milk have been collected from more than six hundred mother-infant pairs for chemical determinations. The growth of infants has been monitored using neurodevelopmental tests, including the Brazelton Neonatal Behavioral Assessment Scale, the Bayley Scale of Infant Development, the Kyoto Scale of Psychological Development, and others. Exposures to dioxin and related compounds, polychlorinated biphenyls, methylmercury, and several heavy metals were assessed. Additionally, since perinatal exposure to organochlorine pesticides may affect the neurodevelopment of children, we examined the effects of those pesticides in the cohort study. In the present study, several organochlorine pesticides were analyzed in human breast milk and placenta from 20 mothers to identify the major pesticide compounds found in the cohort subjects. The relationship between pesticides in breast milk and the placenta was analyzed to examine the utilization of the placenta as the material for exposure assessment. Some information regarding the factors affecting the contamination of breast milk and the placenta with organochlorine pesticides are also discussed.

  6. Identification of prognostic molecular features in the reactive stroma of human breast and prostate cancer.

    Directory of Open Access Journals (Sweden)

    Anne Planche

    Full Text Available Primary tumor growth induces host tissue responses that are believed to support and promote tumor progression. Identification of the molecular characteristics of the tumor microenvironment and elucidation of its crosstalk with tumor cells may therefore be crucial for improving our understanding of the processes implicated in cancer progression, identifying potential therapeutic targets, and uncovering stromal gene expression signatures that may predict clinical outcome. A key issue to resolve, therefore, is whether the stromal response to tumor growth is largely a generic phenomenon, irrespective of the tumor type or whether the response reflects tumor-specific properties. To address similarity or distinction of stromal gene expression changes during cancer progression, oligonucleotide-based Affymetrix microarray technology was used to compare the transcriptomes of laser-microdissected stromal cells derived from invasive human breast and prostate carcinoma. Invasive breast and prostate cancer-associated stroma was observed to display distinct transcriptomes, with a limited number of shared genes. Interestingly, both breast and prostate tumor-specific dysregulated stromal genes were observed to cluster breast and prostate cancer patients, respectively, into two distinct groups with statistically different clinical outcomes. By contrast, a gene signature that was common to the reactive stroma of both tumor types did not have survival predictive value. Univariate Cox analysis identified genes whose expression level was most strongly associated with patient survival. Taken together, these observations suggest that the tumor microenvironment displays distinct features according to the tumor type that provides survival-predictive value.

  7. Study of human breast tissues biochemistry by FT-Raman spectroscopy

    Science.gov (United States)

    Bitar, Renata A.; Jara, Walter Andres A.; Netto, Mário M.; Martinho, Herculano; Ramalho, Leandra Náira Z.; Martin, Airton A.

    2006-02-01

    In this work we employ the Fourier Transform Raman Spectroscopy to study the human breast tissues, both normal and pathological. In the present study we analyze 194 Raman spectra from breast tissues that were separated into 9 groups according to their corresponding histopathological diagnosis, which are as follows: Normal breast tissue, Fibrocystic condition, In Situ Duct Carcinoma, In Situ Duct Carcinoma with Necrosis, Infiltrating Duct Carcinoma, Infiltrating Duct Inflammatory Carcinoma, Infiltrating Duct Medullar Carcinoma, Infiltrating Duct Colloid Carcinoma, and Infiltrating Lobule Carcinoma. We found a strong lipids Raman band, and this structure was identified as abundant in the normal breast tissue spectra. The primary structure of proteins was identified through the shift of the amine acids bands. The identification of the secondary structure of proteins occurred through the peptide bands (Amide I and Amide III). In relation to the carbohydrates, the spectra of duct infiltrating colloid carcinoma, fibrocystic condition, and infiltrating duct carcinoma have been compared and identified. We observed an increase in the intensity of the 800-1200 cm -1 spectral region. This fact could indicate the presence of liquid cystic. We also notice alterations in the peaks in the region of 500 to 600 cm -1 and 2000 to 2100 cm -1 that may suggest changes in the nucleic acids of the cells.

  8. ­­The Effects of Naringenin on Some Human Breast Cancer Cells: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Zahra Akbarzadeh

    2016-06-01

    Full Text Available Background: Breast cancer is the most common cancer in women worldwide. Recently, natural remedies such as Naringenin (Nar - a kind of flavonoids which can be found in grapefruits, oranges, and tomatoes - seem to be interesting. They play a useful role in treatment and chemoprevention because of having pleiotropic molecular mechanisms of action on breast cancer cells.Methods: We performed a PRISMA-directed systematic review to investigate the effects of Naringenin on some human breast cancer cells (MCF-7, T47D, and MDA-MB-231. Tumor size, apoptosis, estrogenic properties, and cytotoxicity were assessed as primary outcomes. The systematic search without restriction was conducted in electronic databases, including PubMed, Scopus, Google scholar, and Cochrane Library.Results: Initially, 6445 articles were identified. After screening their titles and abstracts, 32 studies were selected for text appraisal. Finally, 6 articles which met the inclusion criteria were evaluated. Based on the evaluation, Nar could inhibit both cell proliferation and tumor growth at different concentration. Moreover, it could induce apoptosis.Conclusions: Due to anticancer properties of Nar, some probable mechanisms of these effects are induction of alteration in aromatase and caspase enzymes, and suppression of oestrogen signal transduction pathways. However, more investigations are necessary in the future to decide whether Nar consumption is recommendable as part of breast cancer treatment and control. Also, some clinical trials should be designed to determine the optimal dose for the therapeutic use.

  9. Antitumor activity of colloidal silver on MCF-7 human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Franco-Molina Moisés A

    2010-11-01

    Full Text Available Abstract Background Colloidal silver has been used as an antimicrobial and disinfectant agent. However, there is scarce information on its antitumor potential. The aim of this study was to determine if colloidal silver had cytotoxic effects on MCF-7 breast cancer cells and its mechanism of cell death. Methods MCF-7 breast cancer cells were treated with colloidal silver (ranged from 1.75 to 17.5 ng/mL for 5 h at 37°C and 5% CO2 atmosphere. Cell Viability was evaluated by trypan blue exclusion method and the mechanism of cell death through detection of mono-oligonucleosomes using an ELISA kit and TUNEL assay. The production of NO, LDH, and Gpx, SOD, CAT, and Total antioxidant activities were evaluated by colorimetric assays. Results Colloidal silver had dose-dependent cytotoxic effect in MCF-7 breast cancer cells through induction of apoptosis, shown an LD50 (3.5 ng/mL and LD100 (14 ng/mL (*P Conclusions The present results showed that colloidal silver might be a potential alternative agent for human breast cancer therapy.

  10. Antitumor activity of colloidal silver on MCF-7 human breast cancer cells.

    Science.gov (United States)

    Franco-Molina, Moisés A; Mendoza-Gamboa, Edgar; Sierra-Rivera, Crystel A; Gómez-Flores, Ricardo A; Zapata-Benavides, Pablo; Castillo-Tello, Paloma; Alcocer-González, Juan Manuel; Miranda-Hernández, Diana F; Tamez-Guerra, Reyes S; Rodríguez-Padilla, Cristina

    2010-11-16

    Colloidal silver has been used as an antimicrobial and disinfectant agent. However, there is scarce information on its antitumor potential. The aim of this study was to determine if colloidal silver had cytotoxic effects on MCF-7 breast cancer cells and its mechanism of cell death. MCF-7 breast cancer cells were treated with colloidal silver (ranged from 1.75 to 17.5 ng/mL) for 5 h at 37°C and 5% CO2 atmosphere. Cell Viability was evaluated by trypan blue exclusion method and the mechanism of cell death through detection of mono-oligonucleosomes using an ELISA kit and TUNEL assay. The production of NO, LDH, and Gpx, SOD, CAT, and Total antioxidant activities were evaluated by colorimetric assays. Colloidal silver had dose-dependent cytotoxic effect in MCF-7 breast cancer cells through induction of apoptosis, shown an LD50 (3.5 ng/mL) and LD100 (14 ng/mL) (*P colloidal silver. The present results showed that colloidal silver might be a potential alternative agent for human breast cancer therapy.

  11. Survival differences of CIMP subtypes integrated with CNA information in human breast cancer.

    Science.gov (United States)

    Wang, Huihan; Yan, Weili; Zhang, Shumei; Gu, Yue; Wang, Yihan; Wei, Yanjun; Liu, Hongbo; Wang, Fang; Wu, Qiong; Zhang, Yan

    2017-07-25

    CpG island methylator phenotype of breast cancer is associated with widespread aberrant methylation at specified CpG islands and distinct patient outcomes. However, the influence of copy number contributing to the prognosis of tumors with different CpG island methylator phenotypes is still unclear. We analyzed both genetic (copy number) and epigenetic alterations in 765 breast cancers from The Cancer Genome Atlas data portal and got a panel of 15 biomarkers for copy number and methylation status evaluation. The gene panel identified two groups corresponding to distinct copy number profiles. In status of mere-loss copy number, patients were faced with a greater risk if they presented a higher CpG islands methylation pattern in biomarker panels. But for samples presenting merely-gained copy number, higher methylation level of CpG islands was associated with improved viability. In all, the integration of copy number alteration and methylation information enhanced the classification power on prognosis. Moreover, we found the molecular subtypes of breast cancer presented different distributions in two CpG island methylation phenotypes. Generated by the same set of human methylation 450K data, additional copy number information could provide insights into survival prediction of cancers with less heterogeneity and might help to determine the biomarkers for diagnosis and treatment for breast cancer patients in a more personalized approach.

  12. A New Human-Derived Acellular Dermal Matrix for Breast Reconstruction Available for the European Market: Preliminary Results.

    Science.gov (United States)

    Folli, Secondo; Curcio, Annalisa; Melandri, Davide; Bondioli, Elena; Rocco, Nicola; Catanuto, Giuseppe; Falcini, Fabio; Purpura, Valeria; Mingozzi, Matteo; Buggi, Federico; Marongiu, Francesco

    2018-04-01

    The introduction of acellular dermal matrices (ADMs) contributed to the growing diffusion of direct-to-implant breast reconstruction (DTI-BR) following mastectomy for breast cancer. According to specific legislations, European specialists could not benefit from the use of human-derived ADMs, even though most evidence in the literature are available for this kind of device, showed optimal outcomes in breast reconstruction. The Skin Bank of the Bufalini Hospital (Cesena, Italy) obtained in 2009 the approval for the production and distribution of a new human cadaver-donor-derived ADM (named with the Italian acronym, MODA, for matrice omologa dermica acellulata) from the Italian National Transplant Center and National Health Institute. We report preliminary results of MODA application in direct-to-implant breast reconstruction following nipple-areola complex (NAC)-sparing mastectomy for breast cancer treatment. We prospectively enrolled all women undergoing NAC-sparing mastectomy for breast cancer and DTI-BR in our breast surgical unit from June 2015 to January 2017. We enrolled a selected population without previous chest wall irradiation, not being heavy tobacco smokers or diabetic, with a BMI MODA in direct-to-implant breast reconstruction following NAC-sparing mastectomy for breast cancer treatment. This is particularly relevant for the European market, where no other human-derived devices are available for breast reconstruction due to regulatory restrictions. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  13. Effects of estradiol and medroxyprogesterone acetate on morphology, proliferation and apoptosis of human breast tissue in organ cultures

    International Nuclear Information System (INIS)

    Eigėlienė, Natalija; Härkönen, Pirkko; Erkkola, Risto

    2006-01-01

    Human breast tissue undergoes phases of proliferation, differentiation and regression regulated by changes of the levels of circulating sex hormones during the menstrual cycle or aging. Ovarian hormones also likely play a key role in the etiology and biology of breast cancer. Reports concerning the proliferative effects of steroid hormones on the normal epithelium of human breast have been conflicting. Some studies have shown that steroid hormones may predispose breast epithelial cells to malignant changes by stimulating their proliferation, which is known to be regulated tightly by stromal cells. The aim of this study was to investigate the effects of 17β-estradiol and medroxyprogesterone acetate on proliferation, apoptosis, expression of differentiation markers and steroid hormone receptors in breast epithelium using an in vitro model of freshly isolated human breast tissue, in which a proper interaction of breast epithelium and stroma has been maintained. Human breast tissues were obtained from women undergoing surgery for breast tumours. Peritumoral tissues were excised and explants were cultured for 3 weeks in medium supplemented with E 2 or MPA or with E 2 +MPA. Endpoints included histopathological, histomorphometric and immunohistochemical assessment of the breast explants. Culture of breast explants for 14 or 21 days with steroid hormones increased proliferative activity and the thickness of acinar and ductal epithelium. E 2 -treatment led to hyperplastic epithelial morphology, MPA to hypersecretory single-layered epithelium and E 2 +MPA to multilayered but organised epithelium. The proliferative response to E 2 in comparison to control (p < 0.001) was more pronounced than to MPA (p < 0.05) or E 2 +MPA (p < 0.05) at 7 and 14 days for Ki-67 and PCNA. E 2 treatment also decreased the proportion of apoptotic cells after 7 (p < 0.01) and 14 (p < 0.01) days. In addition, the relative number of ERα, ERβ and PR positive epithelial cells was decreased by all

  14. Utility of FDG-PETCT and magnetic resonance spectroscopy in differentiating between cerebral lymphoma and non-malignant CNS lesions in HIV-infected patients

    Energy Technology Data Exchange (ETDEWEB)

    Westwood, Thomas D., E-mail: tdwestwood@googlemail.com [Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Hogan, Celia, E-mail: celiahogan@hotmail.com [Monsall Unit, Department of Infectious Diseases and Tropical Medicine, North Manchester General Hospital, Pennine Acute Hospitals NHS Trust (United Kingdom); Julyan, Peter J., E-mail: Peter.Julyan@christie.nhs.uk [Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Coutts, Glyn, E-mail: Glyn.Coutts@christie.nhs.uk [Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Bonington, Suzie, E-mail: suzi.bonington@christie.nhs.uk [Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Carrington, Bernadette, E-mail: Bernadette.Carrington@christie.nhs.uk [Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Taylor, Ben, E-mail: Ben.taylor@christie.nhs.uk [Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Khoo, Saye, E-mail: S.H.Khoo@liverpool.ac.uk [Department of Infectious Diseases and Tropical Medicine, Royal Liverpool Hospital, Liverpool (United Kingdom); Bonington, Alec, E-mail: Alec.Bonington@pat.nhs.uk [Monsall Unit, Department of Infectious Diseases and Tropical Medicine, North Manchester General Hospital, Pennine Acute Hospitals NHS Trust (United Kingdom)

    2013-08-15

    Background and purpose: In HIV infected patients, MRI cannot reliably differentiate between central nervous system (CNS) lymphoma and non-malignant CNS lesions, particularly cerebral toxoplasmosis (CTOX). This study prospectively investigates the utility of FDG PET-CT and magnetic resonance spectroscopy (MRS) in discriminating CNS lymphoma from non-malignant CNS lesions in HIV infected patients, and assesses the ability of FDG PET-CT to guide the use of early brain biopsy. Methods: 10 HIV patients with neurological symptoms and contrast enhancing lesions on MRI were commenced on anti-toxoplasmosis therapy before undergoing FDG PET-CT and MRS. Brain biopsies were sought in those with FDG PET-CT suggestive of CNS lymphoma, and in those with a negative FDG PET-CT scan who failed to respond to therapy. Final diagnosis was based on histology or treatment response. Results: Two patients were confirmed to have CNS lymphoma and FDG PET-CT was consistent with this diagnosis in both. Six patients had cerebral toxoplasmosis in all of whom FDG PET-CT was consistent with non-malignant disease. One patient had progressive multifocal leukoencephalopathy (PML), FDG PET-CT was equivocal. One patient had a haemorrhagic brain metastasis and FDG PET-CT wrongly suggested non-malignant disease. MRS was performed successfully in eight subjects: three results were suggestive of CNS lymphoma (one true positive, two false positive), four suggested CTOX (two false negative, two true negative), one scan was equivocal. Conclusion: FDG PET-CT correctly identified all cases of CNS lymphoma and CTOX, supporting its use in this situation. MRS was unhelpful in our cohort.

  15. Utility of FDG-PETCT and magnetic resonance spectroscopy in differentiating between cerebral lymphoma and non-malignant CNS lesions in HIV-infected patients

    International Nuclear Information System (INIS)

    Westwood, Thomas D.; Hogan, Celia; Julyan, Peter J.; Coutts, Glyn; Bonington, Suzie; Carrington, Bernadette; Taylor, Ben; Khoo, Saye; Bonington, Alec

    2013-01-01

    Background and purpose: In HIV infected patients, MRI cannot reliably differentiate between central nervous system (CNS) lymphoma and non-malignant CNS lesions, particularly cerebral toxoplasmosis (CTOX). This study prospectively investigates the utility of FDG PET-CT and magnetic resonance spectroscopy (MRS) in discriminating CNS lymphoma from non-malignant CNS lesions in HIV infected patients, and assesses the ability of FDG PET-CT to guide the use of early brain biopsy. Methods: 10 HIV patients with neurological symptoms and contrast enhancing lesions on MRI were commenced on anti-toxoplasmosis therapy before undergoing FDG PET-CT and MRS. Brain biopsies were sought in those with FDG PET-CT suggestive of CNS lymphoma, and in those with a negative FDG PET-CT scan who failed to respond to therapy. Final diagnosis was based on histology or treatment response. Results: Two patients were confirmed to have CNS lymphoma and FDG PET-CT was consistent with this diagnosis in both. Six patients had cerebral toxoplasmosis in all of whom FDG PET-CT was consistent with non-malignant disease. One patient had progressive multifocal leukoencephalopathy (PML), FDG PET-CT was equivocal. One patient had a haemorrhagic brain metastasis and FDG PET-CT wrongly suggested non-malignant disease. MRS was performed successfully in eight subjects: three results were suggestive of CNS lymphoma (one true positive, two false positive), four suggested CTOX (two false negative, two true negative), one scan was equivocal. Conclusion: FDG PET-CT correctly identified all cases of CNS lymphoma and CTOX, supporting its use in this situation. MRS was unhelpful in our cohort

  16. Clonal proliferation of cultured nonmalignant and malignant human breast epithelia

    International Nuclear Information System (INIS)

    Smith, H.S.; Lan, S.; Ceriani, R.; Hackett, A.J.; Stampfer, M.R.

    1981-01-01

    We have developed a method for clonal growth of human mammary epithelial cells of both nonmalignant and malignant origin. Plating efficiencies of 1 to 50% were obtained by seeding second-passage mammary epithelial cells on fibroblast feeder layers in an enriched medium composed of various hormones and growth factors, as well as conditioned media from three specific human cell lines. Single mammary epithelial cells seeded sparsely onto the fibroblasts underwent at least eight population doublings to form large, readily visible colonies. Optimal colony formation required both feeder cells and the enriched medium. Epithelial colonies containing at least 16 cells were visible 5 days postseeding, and these colonies continued to grow progressively. Plating efficiency and colony size were similar on ultraviolet-irradiated or nonirradiated fibroblasts. The number of colonies formed was proportional to the number of epithelial cells plated. The colonies were identified as epithelial by the presence of human mammary epithelial antigens

  17. Transcriptomic profiling of curcumin-treated human breast stem cells identifies a role for stearoyl-coa desaturase in breast cancer prevention.

    Science.gov (United States)

    Colacino, Justin A; McDermott, Sean P; Sartor, Maureen A; Wicha, Max S; Rozek, Laura S

    2016-07-01

    Curcumin is a potential agent for both the prevention and treatment of cancers. Curcumin treatment alone, or in combination with piperine, limits breast stem cell self-renewal, while remaining non-toxic to normal differentiated cells. We paired fluorescence-activated cell sorting with RNA sequencing to characterize the genome-wide changes induced specifically in normal breast stem cells following treatment with these compounds. We generated genome-wide maps of the transcriptional changes that occur in epithelial-like (ALDH+) and mesenchymal-like (ALDH-/CD44+/CD24-) normal breast stem/progenitor cells following treatment with curcumin and piperine. We show that curcumin targets both stem cell populations by down-regulating expression of breast stem cell genes including ALDH1A3, CD49f, PROM1, and TP63. We also identified novel genes and pathways targeted by curcumin, including downregulation of SCD. Transient siRNA knockdown of SCD in MCF10A cells significantly inhibited mammosphere formation and the mean proportion of CD44+/CD24- cells, suggesting that SCD is a regulator of breast stemness and a target of curcumin in breast stem cells. These findings extend previous reports of curcumin targeting stem cells, here in two phenotypically distinct stem/progenitor populations isolated from normal human breast tissue. We identified novel mechanisms by which curcumin and piperine target breast stem cell self-renewal, such as by targeting lipid metabolism, providing a mechanistic link between curcumin treatment and stem cell self-renewal. These results elucidate the mechanisms by which curcumin may act as a cancer-preventive compound and provide novel targets for cancer prevention and treatment.

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

    Science.gov (United States)

    2018-02-01

    Estrogen Receptor Status; HER2 Positive Breast Carcinoma; Progesterone Receptor Status; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  19. Human adipose tissue from normal and tumoral breast regulates the behavior of mammary epithelial cells.

    Science.gov (United States)

    Pistone Creydt, Virginia; Fletcher, Sabrina Johanna; Giudice, Jimena; Bruzzone, Ariana; Chasseing, Norma Alejandra; Gonzalez, Eduardo Gustavo; Sacca, Paula Alejandra; Calvo, Juan Carlos

    2013-02-01

    Stromal-epithelial interactions mediate both breast development and breast cancer progression. In the present work, we evaluated the effects of conditioned media (CMs) of human adipose tissue explants from normal (hATN) and tumor (hATT) breast on proliferation, adhesion, migration and metalloproteases activity on tumor (MCF-7 and IBH-7) and non-tumor (MCF-10A) human breast epithelial cell lines. Human adipose tissues were obtained from patients and the conditioned medium from hATN and hATT collected after 24 h of incubation. MCF-10A, MCF-7 and IBH-7 cells were grown and incubated with CMs and proliferation and adhesion, as well as migration ability and metalloprotease activity, of epithelial cells after exposing cell cultures to hATN- or hATT-CMs were quantified. The statistical significance between different experimental conditions was evaluated by one-way ANOVA. Tukey's post hoc tests were performed. Tumor and non-tumor breast epithelial cells significantly increased their proliferation activity after 24 h of treatment with hATT-CMs compared to control-CMs. Furthermore, cellular adhesion of these two tumor cell lines was significantly lower with hATT-CMs than with hATN-CMs. Therefore, hATT-CMs seem to induce significantly lower expression or less activity of the components involved in cellular adhesion than hATN-CMs. In addition, hATT-CMs induced pro-MMP-9 and MMP-9 activity and increased the migration of MCF-7 and IBH-7 cells compared to hATN-CMs. We conclude that the microenvironment of the tumor interacts in a dynamic way with the mutated epithelium. This evidence leads to the possibility to modify the tumor behavior/phenotype through the regulation or modification of its microenvironment. We developed a model in which we obtained CMs from adipose tissue explants completely, either from normal or tumor breast. In this way, we studied the contribution of soluble factors independently of the possible effects of direct cell contact.

  20. Expression of Leukemia/Lymphoma-Related Factor (LRF/POKEMON) in Human Breast Carcinoma and Other Cancers

    Science.gov (United States)

    Aggarwal, Anshu; Hunter, William J.; Aggarwal, Himanshu; Silva, Edibaldo D.; Davey, Mary S.; Murphy, Richard F.; Agrawal, Devendra K.

    2010-01-01

    The POK family of proteins plays an important role in not only embryonic development and cell differentiation, but also in oncogenesis. Leukemia/lymphoma-related factor (LRF) belongs to the POK family of transcriptional repressors and is also known as POK erythroid myeloid ontogenic factor (POKEMON), which binds to short transcripts of HIV-1 (FBI-1) and TTF-1 interacting peptide (TIP21). Its oncogenic role is known only in lymphoma, non-small cell lung carcinoma, and malignant gliomas. The functional expression of LRF in human breast carcinoma has not yet been confirmed. The aim of this study was to investigate and compare the expression of LRF in human breast cancer tissues and other human tumors. The expression of LRF mRNA transcripts and protein was observed in twenty human benign and malignant breast biopsy tissues. Expression of LRF was observed in several formalin-fixed tissues by immunohistochemistry and immunofluorescence. All malignant breast tissues expressed mRNA transcripts and protein for LRF. However, 40% and 15% benign breast biopsy tissues expressed LRF mRNA transcripts and protein, respectively. The overall expression of LRF mRNA transcripts and total protein was significantly more in malignant breast tissues than the benign breast tissues. LRF expression was also observed in the nuclei of human colon, renal, lung, hepatocellular carcinomas and thymoma tumor cells. In general, a significantly higher expression of LRF was seen in malignant tissues than in the corresponding benign or normal tissue. Further studies are warranted to determine the malignant role of LRF in human breast carcinoma. PMID:20471975

  1. A prototypical non-malignant epithelial model to study genome dynamics and concurrently monitor micro-RNAs and proteins in situ during oncogene-induced senescence.

    Science.gov (United States)

    Komseli, Eirini-Stavroula; Pateras, Ioannis S; Krejsgaard, Thorbjørn; Stawiski, Konrad; Rizou, Sophia V; Polyzos, Alexander; Roumelioti, Fani-Marlen; Chiourea, Maria; Mourkioti, Ioanna; Paparouna, Eleni; Zampetidis, Christos P; Gumeni, Sentiljana; Trougakos, Ioannis P; Pefani, Dafni-Eleftheria; O'Neill, Eric; Gagos, Sarantis; Eliopoulos, Aristides G; Fendler, Wojciech; Chowdhury, Dipanjan; Bartek, Jiri; Gorgoulis, Vassilis G

    2018-01-10

    Senescence is a fundamental biological process implicated in various pathologies, including cancer. Regarding carcinogenesis, senescence signifies, at least in its initial phases, an anti-tumor response that needs to be circumvented for cancer to progress. Micro-RNAs, a subclass of regulatory, non-coding RNAs, participate in senescence regulation. At the subcellular level micro-RNAs, similar to proteins, have been shown to traffic between organelles influencing cellular behavior. The differential function of micro-RNAs relative to their subcellular localization and their role in senescence biology raises concurrent in situ analysis of coding and non-coding gene products in senescent cells as a necessity. However, technical challenges have rendered in situ co-detection unfeasible until now. In the present report we describe a methodology that bypasses these technical limitations achieving for the first time simultaneous detection of both a micro-RNA and a protein in the biological context of cellular senescence, utilizing the new commercially available SenTraGor TM compound. The method was applied in a prototypical human non-malignant epithelial model of oncogene-induced senescence that we generated for the purposes of the study. For the characterization of this novel system, we applied a wide range of cellular and molecular techniques, as well as high-throughput analysis of the transcriptome and micro-RNAs. This experimental setting has three advantages that are presented and discussed: i) it covers a "gap" in the molecular carcinogenesis field, as almost all corresponding in vitro models are fibroblast-based, even though the majority of neoplasms have epithelial origin, ii) it recapitulates the precancerous and cancerous phases of epithelial tumorigenesis within a short time frame under the light of natural selection and iii) it uses as an oncogenic signal, the replication licensing factor CDC6, implicated in both DNA replication and transcription when over

  2. beta 1 integrin inhibition dramatically enhances radiotherapy efficacy in human breast cancer xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Park, Catherine C.; Park, Catherine C.; Zhang, Hui J.; Yao, Evelyn S.; Park, Chong J.; Bissell, Mina J.

    2008-06-02

    {beta}1 integrin signaling has been shown to mediate cellular resistance to apoptosis after exposure to ionizing radiation (IR). Other signaling molecules that increase resistance include Akt, which promotes cell survival downstream of {beta}1 integrin signaling. We showed previously that {beta}1 integrin inhibitory antibodies, AIIB2, enhance apoptosis and decrease growth in human breast cancer cells in 3 dimensional laminin-rich extracellular matrix (3D lrECM) cultures and in vivo. Here we asked whether AIIB2 could synergize with IR to modify Akt-mediated IR resistance. We used 3D lrECM cultures to test the optimal combination of AIIB2 with IR treatment of two breast cancer cell lines, MCF-7 and HMT3522-T4-2, as well as T4-2 myr-Akt breast cancer colonies or HMT3522-S-1, which form normal organotypic structures in 3D lrECM. Colonies were assayed for apoptosis and {beta}1 integrin/Akt signaling pathways were evaluated using western blot. In addition, mice bearing MCF-7 xenografts were used to validate the findings in 3D lrECM. We report that AIIB2 increased apoptosis optimally post-IR by down regulating Akt in breast cancer colonies in 3D lrECM. In vivo, addition of AIIB2 after IR significantly enhanced tumor growth inhibition and apoptosis compared to either treatment alone. Remarkably, the degree of tumor growth inhibition using AIIB2 plus 2 Gy radiation was similar to that of 8 Gy alone. We showed previously that AIIB2 had no discernible toxicity in mice; here, its addition allowed for a significant reduction in the IR dose that was necessary to achieve comparable growth inhibition and apoptosis in breast cancer xenografts in vivo.

  3. beta 1 integrin inhibition dramatically enhances radiotherapy efficacy in human breast cancer xenografts

    International Nuclear Information System (INIS)

    Park, Catherine C.; Park, Catherine C.; Zhang, Hui J.; Yao, Evelyn S.; Park, Chong J.; Bissell, Mina J.

    2008-01-01

    β1 integrin signaling has been shown to mediate cellular resistance to apoptosis after exposure to ionizing radiation (IR). Other signaling molecules that increase resistance include Akt, which promotes cell survival downstream of β1 integrin signaling. We showed previously that β1 integrin inhibitory antibodies, AIIB2, enhance apoptosis and decrease growth in human breast cancer cells in 3 dimensional laminin-rich extracellular matrix (3D lrECM) cultures and in vivo. Here we asked whether AIIB2 could synergize with IR to modify Akt-mediated IR resistance. We used 3D lrECM cultures to test the optimal combination of AIIB2 with IR treatment of two breast cancer cell lines, MCF-7 and HMT3522-T4-2, as well as T4-2 myr-Akt breast cancer colonies or HMT3522-S-1, which form normal organotypic structures in 3D lrECM. Colonies were assayed for apoptosis and β1 integrin/Akt signaling pathways were evaluated using western blot. In addition, mice bearing MCF-7 xenografts were used to validate the findings in 3D lrECM. We report that AIIB2 increased apoptosis optimally post-IR by down regulating Akt in breast cancer colonies in 3D lrECM. In vivo, addition of AIIB2 after IR significantly enhanced tumor growth inhibition and apoptosis compared to either treatment alone. Remarkably, the degree of tumor growth inhibition using AIIB2 plus 2 Gy radiation was similar to that of 8 Gy alone. We showed previously that AIIB2 had no discernible toxicity in mice; here, its addition allowed for a significant reduction in the IR dose that was necessary to achieve comparable growth inhibition and apoptosis in breast cancer xenografts in vivo

  4. Metabolic fate of neutral human milk oligosaccharides in exclusively breast-fed infants.

    Science.gov (United States)

    Dotz, Viktoria; Rudloff, Silvia; Meyer, Christina; Lochnit, Günter; Kunz, Clemens

    2015-02-01

    Various biological effects have been postulated for human milk oligosaccharides (HMO), as deduced from in vitro, animal, and epidemiological studies. Little is known about their metabolic fate in vivo in the breast-fed infant, which is presented here. Human milk and infant urine and feces were collected from ten mother-child pairs and analyzed by MALDI-TOF MS (/MS), accompanied by high-performance anion-exchange chromatography with pulsed amperometric detection. Previously, we detected intact small and complex HMO in infant urine, which had been absorbed from gut, as verified via intrinsic (13) C-labeling. Our current work reveals the presence of novel HMO metabolites in urine and feces of breast-fed infants. The novel metabolites were identified as acetylated HMOs and other HMO-like structures, produced by the infants or by their gut microbiota. The finding of secretor- or Lewis-specific HMO in the feces/urine of infants fed with nonsecretor or Lewis-negative milk suggested a correspondent modification in the infant. Our study reveals new insights into the metabolism of neutral HMO in exclusively breast-fed infants and provides further indications for multiple factors influencing HMO metabolism and functions that should be considered in future in vivo investigations. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Prolactin response to thyrotropin-releasing hormone in early and advanced human breast cancer

    International Nuclear Information System (INIS)

    Barni, S.; Lissoni, P.; Tancini, G.

    1986-01-01

    While prolactin (PRL) has been shown to stimulate the development of mammary carcinoma in several animal species, its role in human breast cancer remains to be established. To further investigate PRL secretion in human breast cancer, its basal levels and response to thyrotropin-releasing hormone (TRH) were evaluated in 16 patients (6 with no metastases and 10 with metastatic locations). The control group consisted of 19 healthy women. High PRL basal concentrations were seen in 2 patients only; no significant differences were found between the other patients and the normal subjects. The PRL increase induced by TRH administration was significantly higher in patients than in controls. Finally a change in the hormonal secretion was found after chemotherapy in 3 of the 5 patients in whom PRL response to TRH was evaluated either before or 10-12 days after a cycle of intravenous CMF adjuvant chemotherapy. These results demostrate the existence of an exaggerated response of PRL to TRH in patients with breast cancer, even in the presence of normal basal levels. Moreover, they would seem to suggest a possible influence of CMF on PRL response to TRH stimulation

  6. Prevalence of mucosal and cutaneous human papillomavirus in Moroccan breast cancer

    Directory of Open Access Journals (Sweden)

    Amal ElAmrani

    2018-06-01

    Full Text Available Background: Due to recent technical improvements and some encouraging new results, there has been a resurgence of interest in the possibility that a substantial proportion of breast cancers (BCs may be caused by viral infections, including Human papillomavirus (HPV. The aim of this study was to determine the prevalence of mucosal and cutaneous HPV in tumours from Moroccan BC patients. Materials and methods: Frozen tumours from 76 BC cases and 12 controls were evaluated for the presence of 62 HPV-types using highly sensitive assays that combine multiplex polymerase chain reaction and bead-based Luminex technology. Results: HPV DNA was found in 25.0% of BC tumours and only 8.3% of controls. Beta and gamma HPV types were found in 10.5% and 6.6% of BC tumours, respectively. High-risk mucosal types HPV16 and 18 were not detected in the subjects, but other probable/possible high-risk or high-risk -HPV types (HPV51, 52, 58, 59, and 66 were found in 5.3% of BC tumours. Statistical analysis showed no significant difference between, controls, BC cases and the inflammatory status (p > 0.05. Conclusion: HPV DNA was found 3 times as frequently in the BC tumours as in the controls. However, this difference requires confirmation in a larger sample. Keywords: Breast cancer, Human papillomavirus, Inflammatory breast cancer, Type-specific multiplex genotyping, Morocco

  7. Prognostic value of human apurinic/apyrimidinic endonuclease 1 (APE1 expression in breast cancer.

    Directory of Open Access Journals (Sweden)

    Joohyun Woo

    Full Text Available Human apurinic/apyrimidinic endonuclease 1 (APE1 is an essential protein for DNA base excision repair (BER and redox regulation. The ability of cancer cells to recognize DNA damage and initiate DNA repair is an important mechanism for therapeutic resistance. Several recent studies have suggested that APE1 expression levels and/or subcellular dysregulation may be used to indicate the sensitivity of tumors to radiotherapy or chemotherapy. In this study, we assessed the prognostic significance of APE1 and differences in APE1 expression levels according to breast cancer molecular subtypes. We analyzed formalin-fixed, paraffin-embedded tumor tissue sections from 243 cases diagnosed as invasive breast cancer at Ewha Womans University Medical Center between January 2003 and December 2008. Immunohistochemistry was performed and the nuclear level of APE1 was scored by taking into account the percentage of positive cells. Medical records were reviewed to investigate clinicopathologic characteristics. We found that nuclear APE1 high-level expression (proportion ≥50% in breast cancer showed a tendency towards unfavorable prognosis regarding disease-free survival (p = 0.093. However, there was no significant difference in overall survival between low and high-level expression groups (p = 0.294. Interestingly, within the Ki-67 low-level expression group, APE1 low-level expression was significantly associated with poor overall survival (p = 0.007. A significant positive correlation was observed between APE1 nuclear expression and estrogen receptor status (75.7% vs. 59.7%, p = 0.022. Also, the luminal A subtype was the most commonly observed breast cancer subtype in the APE1 high-level expression group (61.6% vs. 45.2%, p = 0.000. This study suggests that APE1 expression may be associated with breast cancer prognosis. In particular, its role as a prognostic factor would be significant for breast cancers with a low Ki-67 proliferation index

  8. Characterization of ERAS, a putative novel human oncogene, in skin and breast

    Energy Technology Data Exchange (ETDEWEB)

    Peña Avalos, B.L. de la

    2014-07-01

    Most human tumors have mutations in genes of the RAS small GTPase protein family. RAS works as a molecular switch for signaling pathways that modulate many aspects of cell behavior, including proliferation, differentiation, motility and death. Oncogenic mutations in RAS prevent GTP hydrolysis, locking RAS in a permanently active state, being the most common mutations in HRAS, KRAS and NRAS. The human RAS family consists of at least 36 different genes, many of which have been scarcely studied. One of these relatively unknown genes is ERAS (ES cell-expressed RAS), which is a constitutively active RAS protein, localized in chromosome X and expressed only in embryonic cells, being undetectable in adult tissues. New high throughput technologies have made it possible to screen complete cancer genomes for identification of mutations associated to cancer. Using the Sleeping Beauty (SB) transposon system, ERAS was identified as a putative novel oncogene in non-melanoma skin and breast cancers. The major aim of this project is to determine the general characteristics of ERAS as a putative novel human oncogene in skin and breast cells. Forced expression of ERAS results in drastic changes in cell shape, proliferation and motility. When ERAS is overexpressed in skin and breast human cells it is mainly localized in the cytoplasmic membrane. ERAS activates the phosphatidylinositol-3-OH kinase (PI3K) pathway but not the mitogen-activated protein kinase (MAPK) pathway. ERAS-expressing cells suffer spontaneous morphologic and phenotypic EMT-like changes, including cytoskeleton reorganization, vimentin and N-cadherin up-regulation and down-regulation of E-cadherin, which can be associated with increased malignancy, and invasive and metastatic potential. Our results suggest that inappropriate expression of ERAS lead to transformation of human cells. (Author)

  9. Development of Human Breast Milk Microbiota-Associated Mice as a Method to Identify Breast Milk Bacteria Capable of Colonizing Gut.

    Science.gov (United States)

    Wang, Xiaoxin; Lu, Huifang; Feng, Zhou; Cao, Jie; Fang, Chao; Xu, Xianming; Zhao, Liping; Shen, Jian

    2017-01-01

    Human breast milk is recognized as one of multiple important sources of commensal bacteria for infant gut. Previous studies searched for the bacterial strains shared between breast milk and infant feces by isolating bacteria and performing strain-level bacterial genotyping, but only limited number of milk bacteria were identified to colonize infant gut, including bacteria from Bifidobacterium , Staphylococcus , Lactobacillus , and Escherichia / Shigella . Here, to identify the breast milk bacteria capable of colonizing gut without the interference of bacteria of origins other than the milk or the necessity to analyze infant feces, normal chow-fed germ-free mice were orally inoculated with the breast milk collected from a mother 2 days after vaginal delivery. According to 16S rRNA gene-based denaturant gradient gel electrophoresis and Illumina sequencing, bacteria at >1% abundance in the milk inoculum were only Streptococcus (56.0%) and Staphylococcus (37.4%), but in the feces of recipient mice were Streptococcus (80.3 ± 2.3%), Corynebacterium (10.0 ± 2.6 %), Staphylococcus (7.6 ± 1.6%), and Propionibacterium (2.1 ± 0.5%) that were previously shown as dominant bacterial genera in the meconium of C-section-delivered human babies; the abundance of anaerobic gut-associated bacteria, Faecalibacterium , Prevotella , Roseburia , Ruminococcus , and Bacteroides , was 0.01-1% in the milk inoculum and 0.003-0.01% in mouse feces; the abundance of Bifidobacterium spp. was below the detection limit of Illumina sequencing in the milk but at 0.003-0.01% in mouse feces. The human breast milk microbiota-associated mouse model may be used to identify additional breast milk bacteria that potentially colonize infant gut.

  10. Activation of SNAT1/SLC38A1 in human breast cancer: correlation with p-Akt overexpression

    International Nuclear Information System (INIS)

    Wang, Kuo; Cao, Fang; Fang, Wenzheng; Hu, Yongwei; Chen, Ying; Ding, Houzhong; Yu, Guanzhen

    2013-01-01

    SNAT1 is a subtype of the amino acid transport system A that has been implicated to play a potential role in cancer development and progression, yet its role in breast cancer remains unclear. In present study, we detected SNAT1 expression in breast cancers and explored its underlying mechanism in promoting breast carcinogenesis. RT-PCR and Western blotting were performed to analyze the transcription and protein levels of SNAT1 in breast cancer cell lines and fresh tissues. Tissue microarray blocks containing breast cancer specimens obtained from 210 patients were constructed. Expression of SNAT1 in these specimens was analyzed using immunohistochemical studies. SNAT1 was down-regulated by SNAT1-shRNA in breast cancer cells and the functional significance was measured. SNAT1 was up-regulated in breast cancer cell lines and breast cancer tissues. Overexpression of SNAT1 was observed in 127 cases (60.5%). Expression of SNAT1 was significantly associated with tumor size, nodal metastasis, advanced disease stage, Ki-67, and ER status. Suppression of endogenous SNAT1 leads to cell growth inhibition, cell cycle arrest, and apoptosis of 4T1 cells and lowered the phosphorylation level of Akt. SNAT1 expression correlated significantly with p-Akt expression in human breast cancer samples. The cross-talk between Akt signaling and SNAT1 might play a critical role in the development and progression of breast cancer, providing an important molecular basis for novel diagnostic markers and new attractive targets in the treatment of breast cancer patients

  11. Anticancer activity of litchi fruit pericarp extract against human breast cancer in vitro and in vivo

    International Nuclear Information System (INIS)

    Wang Xiujie; Yuan Shulan; Wang Jing; Lin Ping; Liu Guanjian; Lu Yanrong; Zhang Jie; Wang, Wendong; Wei Yuquan

    2006-01-01

    Litchi fruit pericarp (LFP) extract contains significant amounts of polyphenolic compounds and exhibits powerful antioxidative activity against fat oxidation in vitro. The purpose of this study is to confirm the anticancer activity of LFP extract on human breast cancer in vitro and in vivo, and to elucidate the mechanism of its activity. Human breast cancer cells were tested in vitro for cytotoxicity, colony formation inhibition, BrdU incorporation, and gene expression profiling after treatment with LFP extract. Seven nude mice bearing human breast infiltrating duct carcinoma orthotopically were tested for its anticancer activity and expression of caspase-3 in vivo by oral administration of 0.3% (0.3 mg/ml) of LFP water-soluble crude ethanolic extract (CEE) for 10 weeks. LFP extract demonstrated a dose- and time-dependent inhibitory effect on cell growth (IC 5 = 80 μg/ml), and it significantly inhibited colony formation and BrdU incorporation of human breast cancer cells. Oligonucleotide microarray analysis identified 41(1.22%) up-regulated and 129 (3.84%) down-regulated genes after LFP water-soluble CEE treatment; the predominantly up-regulated genes were involved in various biological functions including cell cycle regulation and cell proliferation, apoptosis, signal transduction and transcriptional regulation, and extracellular matrix/adhesion molecules; and down-regulated genes were mainly associated with adhesion, invasion, and malignancy of cancer cells. A 40.70% tumor mass volume reduction and significant increase of casepase-3 protein expression were observed in vivo experiment. The findings in this study suggested that LFP extract might have potential anticancer activity on both ER positive and negative breast cancers, which could be attributed, in part, to its DNA damage effect, proliferating inhibition and apoptosis induction of cancer cells through up-regulation and down-regulation of multiple genes involved in cell cycle regulation and cell

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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. - 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

  13. 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.

  14. Expression of the glioma-associated oncogene homolog (GLI) 1 in human breast cancer is associated with unfavourable overall survival

    International Nuclear Information System (INIS)

    Haaf, Anette ten; Bektas, Nuran; Serenyi, Sonja von; Losen, Inge; Arweiler, Elfriede Christel; Hartmann, Arndt; Knüchel, Ruth; Dahl, Edgar

    2009-01-01

    The transcription factor GLI1, a member of the GLI subfamily of Krüppel-like zinc finger proteins is involved in signal transduction within the hedgehog pathway. Aberrant hedgehog signalling has been implicated in the development of different human tumour entities such as colon and lung cancer and increased GLI1 expression has been found in these tumour entities as well. In this study we questioned whether GLI1 expression might also be important in human breast cancer development. Furthermore we correlated GLI1 expression with histopathological and clinical data to evaluate whether GLI1 could represent a new prognostic marker in breast cancer treatment. Applying semiquantitative realtime PCR analysis and immunohistochemistry (IHC) GLI1 expression was analysed in human invasive breast carcinomas (n = 229) in comparison to normal human breast tissues (n = 58). GLI1 mRNA expression was furthermore analysed in a set of normal (n = 3) and tumourous breast cell lines (n = 8). IHC data were statistically interpreted using SPSS version 14.0. Initial analysis of GLI1 mRNA expression in a small cohort of (n = 5) human matched normal and tumourous breast tissues showed first tendency towards GLI1 overexpression in human breast cancers. However only a small sample number was included into these analyses and values for GLI1 overexpression were statistically not significant (P = 0.251, two-tailed Mann-Whitney U-test). On protein level, nuclear GLI1 expression in breast cancer cells was clearly more abundant than in normal breast epithelial cells (P = 0.008, two-tailed Mann-Whitney U-test) and increased expression of GLI1 protein in breast tumours significantly correlated with unfavourable overall survival (P = 0.019), but also with higher tumour stage (P < 0.001) and an increased number of tumour-positive axillar lymph nodes (P = 0.027). Interestingly, a highly significant correlation was found between GLI1 expression and the expression of SHH, a central upstream molecule of

  15. Iron concentrations in breast milk and selected maternal factors of human milk bank donors.

    Science.gov (United States)

    Mello-Neto, Julio; Rondó, Patrícia H C; Morgano, Marcelo A; Oshiiwa, Marie; Santos, Mariana L; Oliveira, Julicristie M

    2010-05-01

    The aim of this study was to evaluate the relationship between iron concentration in mature breast milk and characteristics of 136 donors of a Brazilian milk bank. Iron, vitamin A, zinc, and copper concentrations were assessed in human milk and maternal blood. Data were collected on maternal anthropometrics, obstetric, socioeconomic, demographic, and lifestyle factors. Iron, zinc, and copper in milk and zinc and copper in blood were detected by spectrophotometry. Vitamin A in milk and blood was determined by high-performance liquid chromatography. Hemoglobin was measured by electronic counting and serum iron and ferritin by colorimetry and chemoluminescence, respectively. Transferrin and ceruloplasmin were determined by nephelometry. According to multivariate linear regression analysis, iron in milk was positively associated with vitamin A in milk and with smoking but negatively associated with timing of breast milk donation (P milk of Brazilian donors may be influenced by nutritional factors and smoking.

  16. Lack of Evidence for a Relationship between High Risk Human Papillomaviruses and Breast Cancer in Iranian Patients.

    Science.gov (United States)

    Doosti, Masoud; Bakhshesh, Mehran; Zahir, Shokouh Taghipour; Shayestehpour, Mohammad; Karimi-Zarchi, Mojgan

    2016-01-01

    Whether there is any relationship between human papilloma virus (HPV) and breast carcinoma is not clear. Some previous studies have indicated a possible role in oncogenesis in the breast. In this study, we therefore analyzed the presence of HPV infection in breast tissues of Iranian women from Yazd city. In a cross-sectional study, formalin-fixed paraffin-embedded tissues from 87 patients with breast cancer and 84 cases with breast fibrocystic lesions (control group) were selected from a tissue archive. Grade of tumors and fibrocystic tissues were determined by two pathologists. The nested-PCR method was performed for detection of HPVs in samples. HPV genotypes were determined by sequencing and the phylogenetic tree depicted by MEGA software. Of the 87 women with breast cancer, 22.9% (20 isolates) had positive results for HPV DNA. In the control group no HPV was detected. The HPV genotypes in positive samples were HPV-16 (35%) HPV-18 (15%), HPV-6 (45%) and HPV-11 (5%). The data did not approved a significant correlation between tissue pathology of breast cancer and the HPV genotype frequency. The data did not provide any evidence for a role of high risk HPV types in oncogenesis in the breast.

  17. Cullin1 is a novel marker of poor prognosis and a potential therapeutic target in human breast cancer.

    Science.gov (United States)

    Bai, J; Yong, H M; Chen, F F; Mei, P J; Liu, H; Li, C; Pan, Z Q; Wu, Y P; Zheng, J N

    2013-08-01

    To investigate the role of Cullin1 (Cul1) in the development of breast cancer, we examined the expression of Cul1 in breast cancer tissues and analyzed the correlation between Cul1 expression and clinicopathologic variables and patients survival. We evaluated the Cul1 expression by immunohistochemistry using a tissue microarray (TMA) which includes 393 breast cancer tissues. We also studied the role of Cul1 in breast cancer cell proliferation, migration and invasion by carrying out CCK8 cell proliferation assay, cell migration and invasion assay. The Cul1 expression was significantly correlated with breast cancer histology grade (P = 0.000), estrogen receptor status (P = 0.001), progesterone receptor status (P = 0.001) and human epidermal growth factor receptor 2 status (P = 0.002). Furthermore, we showed a strong correlation between high Cul1 expression and worse 5-year overall and disease-specific survival rates in breast cancer patients (P = 0.026 and P = 0.015, respectively). Finally, we found that Cul1 knockdown inhibits cell proliferation, migration and invasion abilities. Cul1 overexpression is significantly correlated with breast cancer progression and predicts worse survival. Cul1 regulates breast cancer cell proliferation, migration and invasion.

  18. Autophagy inhibition enhances apigenin-induced apoptosis in human breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    Xuchen Cao; Bowen Liu; Wenfeng Cao; Weiran Zhang; Fei Zhang; Hongmeng Zhao; Ran Meng

    2013-01-01

    Apigenin (4',5,7-trihydroxyflavone) is a member of the flavone subclass of flavonoids present in fruits and vegetables.The involvement of autophagy in the apigenin-induced apoptotic death of human breast cancer cells was investigated.Cell proliferation and viability were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenic assays.Flow cytometry,fluorescent staining and Western blot analysis were employed to detect apoptosis and autophagy,and the role of autophagy was assessed using autophagy inhibitors.Apigenin dose-and time-dependently repressed the proliferation and clonogenic survival of the human breast cancer T47D and MDA-MB-231 cell lines.The death of T47D and MDA-MB-231 cells was due to apoptosis associated with increased levels of Caspase3,PARP cleavage and Bax/Bcl-2 ratios.The results from flow cytometry and fluorescent staining also verified the occurrence of apoptosis.In addition,the apigenin-treated cells exhibited autophagy,as characterized by the appearance of autophagosomes under fluorescence microscopy and the accumulation of acidic vesicular organelles (AVOs)by flow cytometry.Furthermore,the results of the Western blot analysis revealed that the level of LC3-Ⅱ,the processed form of LC3-Ⅰ,was increased.Treatment with the autophagy inhibitor,3-methyladenine (3-MA),significantly enhanced the apoptosis induced by apigenin,which was accompanied by an increase in the level of PARP cleavage.Similar results were also confirmed by flow cytometry and fluorescence microscopy.These results indicate that apigenin has apoptosis-and autophagy-inducing effects in breast cancer cells.Autophagy plays a cyto-protective role in apigenin-induced apoptosis,and the combination of apigenin and an autophagy inhibitor may be a promising strategy for breast cancer control.

  19. Monitoring Dynamic Interactions between Breast Cancer Cells and Human Bone Tissue in a Co-Culture Model

    Science.gov (United States)

    Contag, Christopher H.; Lie, Wen-Rong; Bammer, Marie C.; Hardy, Jonathan W.; Schmidt, Tobi L.; Maloney, William J.; King, Bonnie L.

    2015-01-01

    Purpose Bone is a preferential site of breast cancer metastasis and models are needed to study this process at the level of the microenvironment. We have used bioluminescence imaging (BLI) and multiplex biomarker immunoassays to monitor dynamic breast cancer cell behaviors in co-culture with human bone tissue. Procedures Femur tissue fragments harvested from hip replacement surgeries were co-cultured with luciferase-positive MDA-MB-231-fLuc cells. BLI was performed to quantify breast cell division and track migration relative to bone tissue. Breast cell colonization of bone tissues was assessed with immunohistochemistry. Biomarkers in co-culture supernatants were profiled with MILLIPLEX® immunoassays. Results BLI demonstrated increased MDA-MB-231-fLuc proliferation (pbones, and revealed breast cell migration toward bone. Immunohistochemistry illustrated MDA-MB-231-fLuc colonization of bone, and MILLIPLEX® profiles of culture supernatants suggested breast/bone crosstalk. Conclusions Breast cell behaviors that facilitate metastasis occur reproducibly in human bone tissue co-cultures and can be monitored and quantified using BLI and multiplex immunoassays. PMID:24008275

  20. MOLECULAR DOCKING OF COMPOUNDS FROM Chaetomium Sp. AGAINST HUMAN ESTROGEN RECEPTOR ALPHA IN SEARCHING ANTI BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Maywan Hariono

    2016-05-01

    Full Text Available A study on molecular docking-based virtual screening has been conducted to select virtual hit of compounds, reported its existence in fungal endophytes of Chaetomium sp. as cytotoxic agent of breast cancer. The ligands were docked into Human Estrogen Receptor alpha (HERa as the protein which regulates the breast cancer growth via estradiol-estrogen receptor binding intervention. The results showed that two compounds bearing xanthone and two compounds bearing benzonaphtyridinedione scaffolds were selected as virtual hit ligands for HERa leading to the conclusion that these compounds were good to be developed as anti breast cancer.

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

    International Nuclear Information System (INIS)

    Peterson, Sarah M; Concino, Michael F; Liaw, Lucy; Martini, Paolo GV; Iskenderian, Andrea; Cook, Lynette; Romashko, Alla; Tobin, Kristen; Jones, Michael; Norton, Angela; Gómez-Yafal, Alicia; Heartlein, Michael W

    2010-01-01

    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

  2. Persistent pesticides in human breast milk and chryptorchidism

    DEFF Research Database (Denmark)

    Damgaard, Ida N.; Skakkebæk, Niels E.; Toppari, Jorma

    2006-01-01

    INTRODUCTION: Prenatal exposure to some pesticides can adversely affect male reproductive health in animals. We investigated a possible human association between maternal exposure to 27 organochlorine compounds used as pesticides and cryptorchidism among male children. DESIGN: Within a prospective...... birth cohort, we performed a case-control study; 62 milk samples from mothers of cryptorchid boys and 68 from mothers of healthy boys were selected. Milk was collected as individual pools between 1 and 3 months postpartum and analyzed for 27 organochlorine pesticides. RESULTS: Eight organochlorine......-endosulfan, cis-HE, chlordane (cis-, trans-) oxychlordane, methoxychlor, OCS, and dieldrin] were measured in higher median concentrations in case milk than in control milk. Apart from trans-chlordane (p = 0.012), there were no significant differences between cryptorchid and healthy boys for individual chemicals...

  3. Elevated osteopontin and thrombospondin expression identifies malignant human breast carcinoma but is not indicative of metastatic status

    International Nuclear Information System (INIS)

    Wang-Rodriguez, Jessica; Urquidi, Virginia; Rivard, Amber; Goodison, Steve

    2003-01-01

    Our previous characterization of a human breast tumor metastasis model identified several candidate metastasis genes. The expression of osteopontin (OPN) correlated with the metastatic phenotype, whereas thrombospondin-1 (TSP-1) and tyrosinase-related protein-1 (TYRP-1) correlated with the nonmetastatic phenotype of independent MDA-MB-435 cell lines implanted orthotopically into athymic mice. The aim of the present study was to examine the cellular distribution of these molecules in human breast tissue and to determine whether the relative expression level of these three genes is associated with human breast tumor metastasis. Sixty-eight fresh, frozen specimens including 31 primary infiltrating ductal carcinomas, 22 nodal metastases, 10 fibroadenomas, and five normal breast tissues were evaluated for OPN expression, TSP-1 expression and TYRP-1 expression. Immunohistochemistry was performed to monitor the cellular distribution and to qualitatively assess expression. Quantitative analysis was achieved by enrichment of breast epithelial cells using laser-capture microdissection and subsequent real-time, quantitative PCR. The epithelial components of the breast tissue were the source of OPN and TSP-1 expression, whereas TYRP-1 was present in both the epithelial and stromal components. Both OPN and TSP-1 expression were significantly higher in malignant epithelial sources over normal and benign epithelial sources, but no difference in expression levels was evident between primary tumors with or without metastases, nor between primary and metastatic carcinomas. Elevated expression of OPN and TSP-1 may play a role in the pathogenesis of breast cancer. The multiplex analysis of these molecules may enhance our ability to diagnose and/or prognosticate human breast malignancy

  4. Endocrine sensitivity of the receptor-positive T61 human breast carcinoma serially grown in nude mice

    DEFF Research Database (Denmark)

    Brünner, N; Spang-Thomsen, M; Skovgaard Poulsen, H

    1985-01-01

    A study was made on the effect of ovariectomy, 17 beta-oestradiol, and tamoxifen on the oestrogen and progesterone receptor-positive T61 human breast carcinoma grown in nude mice. The effect of the treatment was evaluated by the specific growth delay calculated on the basis of Gompertz growth cur...... but is not a sufficiently clear marker to allow prediction of the endocrine sensitivity of individual breast tumours....

  5. N-3 Polyunsaturated Fatty Acids of Marine Origin and Multifocality in Human Breast Cancer.

    Science.gov (United States)

    Ouldamer, Lobna; Goupille, Caroline; Vildé, Anne; Arbion, Flavie; Body, Gilles; Chevalier, Stephan; Cottier, Jean Philippe; Bougnoux, Philippe

    2016-01-01

    The microenvironment of breast epithelial tissue may contribute to the clinical expression of breast cancer. Breast epithelial tissue, whether healthy or tumoral, is directly in contact with fat cells, which in turn could influence tumor multifocality. In this pilot study we investigated whether the fatty acid composition of breast adipose tissue differed according to breast cancer focality. Twenty-three consecutive women presenting with non-metastatic breast cancer underwent breast-imaging procedures including Magnetic Resonance Imaging prior to treatment. Breast adipose tissue specimens were collected during breast surgery. We established a biochemical profile of adipose tissue fatty acids by gas chromatography. We assessed whether there were differences according to breast cancer focality. We found that decreased levels in breast adipose tissue of docosahexaenoic and eicosapentaenoic acids, the two main polyunsaturated n-3 fatty acids of marine origin, were associated with multifocality. These differences in lipid content may contribute to mechanisms through which peritumoral adipose tissue fuels breast cancer multifocality.

  6. Stromal cell derived factor-1: its influence on invasiveness and migration of breast cancer cells in vitro, and its association with prognosis and survival in human breast cancer

    International Nuclear Information System (INIS)

    Kang, Hua; Watkins, Gareth; Parr, Christian; Douglas-Jones, Anthony; Mansel, Robert E; Jiang, Wen G

    2005-01-01

    Stromal cell-derived factor (SDF)-1 (CXC chemokine ligand-12) is a member of the CXC subfamily of chemokines, which, through its cognate receptor (CXC chemokine receptor [CXCR]4), plays an important role in chemotaxis of cancer cells and in tumour metastasis. We conducted the present study to evaluate the effect of SDF-1 on the invasiveness and migration of breast cancer cells, and we analyzed the expression of SDF-1 and its relation to clinicopathological features and clinical outcomes in human breast cancer. Expression of SDF-1 mRNA in breast cancer, endothelial (HECV) and fibroblast (MRC5) cell lines and in human breast tissues were studied using RT-PCR. MDA-MB-231 cells were transfected with a SDF-1 expression vector, and their invasiveness and migration was tested in vitro. In addition, the expression of SDF-1 was investigated using immunohistochemistry and quantitative RT-PCR in samples of normal human mammary tissue (n = 32) and mammary tumour (n = 120). SDF-1 expression was identified in MRC5, MDA-MB-435s and MDA-MB-436 cell lines, but CXCR4 expression was detected in all cell lines and breast tissues. An autocrine loop was created following transfection of MDA-MB-231 (which was CXCR4 positive and SDF-1 negative) with a mammalian expression cassette encoding SDF-1 (MDA-MB-231SDF1 +/+ ) or with control plasmid pcDNA4/GFP (MDA-MB-231 +/- ). MDA-MB-231SDF1 +/+ cells exhibited significantly greater invasion and migration potential (in transfected cells versus in wild type and empty MDA-MB-231 +/- ; P < 0.01). In mammary tissues SDF-1 staining was primarily seen in stromal cells and weakly in mammary epithelial cells. Significantly higher levels of SDF-1 were seen in node-positive than in node-negative tumours (P = 0.05), in tumours that metastasized (P = 0.05), and tumours from patients who died (P = 0.03) than in tumours from patients who were disease free. It was most notable that levels of SDF-1 correlated significantly with overall survival (P = 0.001) and

  7. Dose and dose rate extrapolation factors for malignant and non-malignant health endpoints after exposure to gamma and neutron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Tran, Van; Little, Mark P. [National Cancer Institute, Radiation Epidemiology Branch, Rockville, MD (United States)

    2017-11-15

    Murine experiments were conducted at the JANUS reactor in Argonne National Laboratory from 1970 to 1992 to study the effect of acute and protracted radiation dose from gamma rays and fission neutron whole body exposure. The present study reports the reanalysis of the JANUS data on 36,718 mice, of which 16,973 mice were irradiated with neutrons, 13,638 were irradiated with gamma rays, and 6107 were controls. Mice were mostly Mus musculus, but one experiment used Peromyscus leucopus. For both types of radiation exposure, a Cox proportional hazards model was used, using age as timescale, and stratifying on sex and experiment. The optimal model was one with linear and quadratic terms in cumulative lagged dose, with adjustments to both linear and quadratic dose terms for low-dose rate irradiation (<5 mGy/h) and with adjustments to the dose for age at exposure and sex. After gamma ray exposure there is significant non-linearity (generally with upward curvature) for all tumours, lymphoreticular, respiratory, connective tissue and gastrointestinal tumours, also for all non-tumour, other non-tumour, non-malignant pulmonary and non-malignant renal diseases (p < 0.001). Associated with this the low-dose extrapolation factor, measuring the overestimation in low-dose risk resulting from linear extrapolation is significantly elevated for lymphoreticular tumours 1.16 (95% CI 1.06, 1.31), elevated also for a number of non-malignant endpoints, specifically all non-tumour diseases, 1.63 (95% CI 1.43, 2.00), non-malignant pulmonary disease, 1.70 (95% CI 1.17, 2.76) and other non-tumour diseases, 1.47 (95% CI 1.29, 1.82). However, for a rather larger group of malignant endpoints the low-dose extrapolation factor is significantly less than 1 (implying downward curvature), with central estimates generally ranging from 0.2 to 0.8, in particular for tumours of the respiratory system, vasculature, ovary, kidney/urinary bladder and testis. For neutron exposure most endpoints, malignant and

  8. Prevalence and factors associated with breast milk donation in banks that receive human milk in primary health care units.

    Science.gov (United States)

    Meneses, Tatiana Mota Xavier de; Oliveira, Maria Inês Couto de; Boccolini, Cristiano Siqueira

    To estimate the prevalence and to analyze factors associated with breast milk donation at primary health care units in order to increase the human milk bank reserves. Cross-sectional study carried out in 2013 in Rio de Janeiro, Brazil. A representative sample of 695 mothers of children younger than 1 year attended to at the nine primary health care units with human milk donation services were interviewed. A hierarchical approach was used to obtain adjusted prevalence ratios (APR) by Poisson regression with robust variance. The final model included the variables associated with breast milk donation (p≤0.05). 7.3% of the mothers had donated breast milk. Having been encouraged to donate breast milk by healthcare professionals, relatives, or friends (APR=7.06), receiving information on breast milk expression by the primary health care unit (APR=3.65), and receiving help from the unit professionals to breastfeed (APR=2.24) were associated with a higher prevalence of donation. Admission of the newborn to the neonatal unit was associated with a lower prevalence of donation (APR=0.09). Encouragement to breast milk donation, and information and help provided by primary health care unit professionals to breastfeeding were shown to be important for the practice of human milk donation. Copyright © 2017. Published by Elsevier Editora Ltda.

  9. Prevalence and factors associated with breast milk donation in banks that receive human milk in primary health care units,

    Directory of Open Access Journals (Sweden)

    Tatiana Mota Xavier de Meneses

    Full Text Available Abstract Objective: To estimate the prevalence and to analyze factors associated with breast milk donation at primary health care units in order to increase the human milk bank reserves. Methods: Cross-sectional study carried out in 2013 in Rio de Janeiro, Brazil. A representative sample of 695 mothers of children younger than 1 year attended to at the nine primary health care units with human milk donation services were interviewed. A hierarchical approach was used to obtain adjusted prevalence ratios (APR by Poisson regression with robust variance. The final model included the variables associated with breast milk donation (p ≤ 0.05. Results: 7.3% of the mothers had donated breast milk. Having been encouraged to donate breast milk by healthcare professionals, relatives, or friends (APR = 7.06, receiving information on breast milk expression by the primary health care unit (APR = 3.65, and receiving help from the unit professionals to breastfeed (APR = 2.24 were associated with a higher prevalence of donation. Admission of the newborn to the neonatal unit was associated with a lower prevalence of donation (APR = 0.09. Conclusions: Encouragement to breast milk donation, and information and help provided by primary health care unit professionals to breastfeeding were shown to be important for the practice of human milk donation.

  10. “Exosomics”—A Review of Biophysics, Biology and Biochemistry of Exosomes With a Focus on Human Breast Milk

    Directory of Open Access Journals (Sweden)

    Carolina de la Torre Gomez

    2018-03-01

    Full Text Available Exosomes are biomolecular nanostructures released from cells. They carry specific biomolecular information and are mainly researched for their exquisite properties as a biomarker source and delivery system. We introduce exosomes in the context of other extracellular vesicles, describe their biophysical isolation and characterisation and discuss their biochemical profiling. Motivated by our interest in early-life nutrition and health, and corresponding studies enrolling lactating mothers and their infants, we zoom into exosomes derived from human breast milk. We argue that these should be more extensively studied at proteomic and micronutrient profiling level, because breast milk exosomes provide a more specific window into breast milk quality from an immunological (proteomics and nutritional (micronutrient perspective. Such enhanced breast milk exosome profiling would thereby complement and enrich the more classical whole breast milk analysis and is expected to deliver more functional insights than the rather descriptive analysis of human milk, or larger fractions thereof, such as milk fat globule membrane. We substantiate our arguments by a bioinformatic analysis of two published proteomic data sets of human breast milk exosomes.

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

    International Nuclear Information System (INIS)

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

    2012-01-01

    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

  12. 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

  13. Reduced-intensity conditioning for the treatment of malignant and life-threatening non-malignant disorders.

    Science.gov (United States)

    Slavin, Shimon; Aker, Mehmet; Shapira, Michael Y; Resnick, Igor; Bitan, Menachem; Or, Reuven

    2003-01-01

    Allogeneic bone marrow or blood stem cell transplantation (BMT) represents an important therapeutic tool for the treatment of an otherwise incurable broad spectrum of malignant and non-malignant diseases. Until recently, BMT was used primarily to replace a malignant, genetically abnormal or deficient immunohematopoietic compartment and therefore, highly toxic myeloablative regimens were considered mandatory for more effective eradication of all undesirable host-derived hematopoietic cells, including stem cells and their progeny. Our preclinical and ongoing clinical studies indicated that much more effective eradication of host immunohematopoietic system cells can be mediated by donor lymphocytes in the process of adoptive allogeneic cell therapy following BMT. Thus, eradication of all malignant cells, especially in patients with CML and, to a lesser extent, in patients with other hematologic malignancies can be accomplished despite complete resistance of puch tumor cells to maximally tolerated doses of chemoradiotherapy. Our cumulative experience suggested that graft-versus-malignancy effects might be used as a tool for eradication of otherwise resistant tumor cells of host origin. We speculated that the therapeutic benefit of BMT may be improved by using safer conditioning for engraftment of donor stem cells induce host-versus-graft unresponsiveness to enable engraftment of donor lymphocytes for subsequent induction of graft-versus-malignancy effects, or even graft-versus-autoimmunity and graft-versus-genetically abnormal cells. In other words, focusing on more selective and smarter rather than stronger modalities. Effective BMT procedures may be accomplished without lethal conditioning of the host, using a new, well-tolerated and user-friendly non-myeloablative regimen, thus eliminating or minimizing immediate and late procedure-related toxicity and mortality. It appears that initial induction of graft tolerance, mediated by engraftment of donor stem cells, leads

  14. Transcriptional and epigenetic regulation of KIAA1199 gene expression in human breast cancer.

    Directory of Open Access Journals (Sweden)

    Cem Kuscu

    Full Text Available Emerging evidence has demonstrated that upregulated expression of KIAA1199 in human cancer bodes for poor survival. The regulatory mechanism controlling KIAA1199 expression in cancer remains to be characterized. In the present study, we have isolated and characterized the human KIAA1199 promoter in terms of regulation of KIAA1199 gene expression. A 3.3 kb fragment of human genomic DNA containing the 5'-flanking sequence of the KIAA1199 gene possesses both suppressive and activating elements. Employing a deletion mutagenesis approach, a 1.4 kb proximal region was defined as the basic KIAA1199 promoter containing a TATA-box close to the transcription start site. A combination of 5'-primer extension study with 5'RACE DNA sequencing analysis revealed one major transcription start site that is utilized in the human KIAA1199 gene. Bioinformatics analysis suggested that the 1.4 kb KIAA1199 promoter contains putative activating regulatory elements, including activator protein-1(AP-1, Twist-1, and NF-κB sites. Sequential deletion and site-direct mutagenesis analysis demonstrated that the AP-1 and distal NF-κB sites are required for KIAA1199 gene expression. Further analyses using an electrophoretic mobility-shift assay and chromatin immunoprecipitation confirmed the requirement of these cis- and trans-acting elements in controlling KIAA1199 gene expression. Finally, we found that upregulated KIAA1199 expression in human breast cancer specimens correlated with hypomethylation of the regulatory region. Involvement of DNA methylation in regulation of KIAA1199 expression was recapitulated in human breast cancer cell lines. Taken together, our study unraveled the regulatory mechanisms controlling KIAA1199 gene expression in human cancer.

  15. Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles

    International Nuclear Information System (INIS)

    Klopfleisch, Robert; Lenze, Dido; Hummel, Michael; Gruber, Achim D

    2010-01-01

    Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent. Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer. Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors. Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs are in some aspects suitable as a

  16. Gene expression profiling of human breast tissue samples using SAGE-Seq.

    Science.gov (United States)

    Wu, Zhenhua Jeremy; Meyer, Clifford A; Choudhury, Sibgat; Shipitsin, Michail; Maruyama, Reo; Bessarabova, Marina; Nikolskaya, Tatiana; Sukumar, Saraswati; Schwartzman, Armin; Liu, Jun S; Polyak, Kornelia; Liu, X Shirley

    2010-12-01

    We present a powerful application of ultra high-throughput sequencing, SAGE-Seq, for the accurate quantification of normal and neoplastic mammary epithelial cell transcriptomes. We develop data analysis pipelines that allow the mapping of sense and antisense strands of mitochondrial and RefSeq genes, the normalization between libraries, and the identification of differentially expressed genes. We find that the diversity of cancer transcriptomes is significantly higher than that of normal cells. Our analysis indicates that transcript discovery plateaus at 10 million reads/sample, and suggests a minimum desired sequencing depth around five million reads. Comparison of SAGE-Seq and traditional SAGE on normal and cancerous breast tissues reveals higher sensitivity of SAGE-Seq to detect less-abundant genes, including those encoding for known breast cancer-related transcription factors and G protein-coupled receptors (GPCRs). SAGE-Seq is able to identify genes and pathways abnormally activated in breast cancer that traditional SAGE failed to call. SAGE-Seq is a powerful method for the identification of biomarkers and therapeutic targets in human disease.

  17. Comparison between hemosiderin and Technetium-99 in sentinel lymph node biopsy in human breast cancer

    International Nuclear Information System (INIS)

    Vasques, Paulo Henrique Diogenes; Aquino, Ranniere Gurgel Furtado de; Pinheiro, Luiz Gonzaga Porto; Torres, Roberto Vitor Almeida; Bezerra, Jose Lucas Martins; Brasileiro, Luis Porto

    2015-01-01

    Purpose: To assess the safety and potential equivalence of the use of hemosiderin compared to the Technetium-99 in sentinel lymph node biopsy in human breast cancer. Methods: Non-random sample of 14 volunteer women diagnosed with breast cancer with primary tumors (T1/T2) and clinically tumor-free axilla were submitted to the identification of sentinel lymph node using hemosiderin obtained from autologous blood injected in the periareolar region 24h before surgery on an outpatient basis. Patients received preoperative subareolar intradermal injection of Technetium-99 in the immediate preoperative period. Patients were submitted to sentinel lymph node biopsy, with incision in the axillary fold guided by Gamma-Probe, dissection by planes until the identification of the point of maximum uptake of Technetium-99, identifying the marked nodes and their colors. All surgical specimens were sent for pathological and immunohistochemical study. Results: The results showed no evidence of side effects and/or allergic and non-allergic reactions in patients submitted to SLNB with hemosiderin. The SLN identification rate per patient was 100%. SLNB identification rate per patient with hemosiderin was the same as that of Technetium, with a concordance rate of 100% between the methods. Conclusion: Hemosiderin is a safe dye that is equivalent to Technetium in breast sentinel lymph node biopsy. (author)

  18. Immunophenotypic characterization of human T cells after in vitro exposure to different silicone breast implant surfaces.

    Directory of Open Access Journals (Sweden)

    Giuseppe Cappellano

    Full Text Available The most common complication of silicone breast implants is capsular contracture (massive scar formation around the implant. We postulate that capsular contracture is always a sequel to inflammatory processes, with both innate and adaptive immune mechanisms participating. In general, fibroblasts and macrophages have been used as cell types to evaluate in vitro the biocompatibility of breast implant surfaces. Moreover, also T cells have been found at the implant site at the initial stage of fibrous capsule formation. However, only few studies have addressed the influence of surfaces with different textures on T-cell responses. The aim of the present study was to investigate the immune response of human peripheral blood mononuclear cells (PBMC to commercially available silicone breast implants in vitro. PBMC from healthy female blood donors were cultured on each silicone surface for 4 days. Proliferation and phenotype of cultured cells were assessed by flow cytometry. Cytokine levels were determined by multiplex and real-time assay. We found that silicone surfaces do not induce T-cell proliferation, nor do they extensively alter the proportion of T cell subsets (CD4, CD8, naïve, effector memory. Interestingly, cytokine profiling identified matrix specific differences, especially for IL-6 and TNF-α on certain surface topographies that could lead to increased fibrosis.

  19. Synergistic effects of retinoic acid and tamoxifen on human breast cancer cells: Proteomic characterization

    International Nuclear Information System (INIS)

    Wang Ying; He Qingyu; Chen Hongming; Chiu Jenfu

    2007-01-01

    The anti-estrogen tamoxifen and vitamin A-related compound, all-trans retinoic acid (RA), in combination act synergistically to inhibit the growth of MCF-7 human breast cancer cells. In the present study, we applied two-dimensional gel electrophoresis based proteomic approach to globally analyze this synergistic effect of RA and tamoxifen. Proteomic study revealed that multiple clusters of proteins were involved in RA and tamoxifen-induced apoptosis in MCF-7 breast cancer cells, including post-transcriptional and splicing factors, proteins related to cellular proliferation or differentiation, and proteins related to energy production and internal degradation systems. The negative growth factor-transforming growth factor β (TGFβ) was secreted by RA and/or tamoxifen treatment and was studies as a potential mediator of the synergistic effects of RA and tamoxifen in apoptosis. By comparing protein alterations in treatments of RA and tamoxifen alone or in combination to those of TGFβ treatment, or co-treatment with TGFβ inhibitor SB 431542, proteomic results showed that a number of proteins were involved in TGFβ signaling pathway. These results provide valuable insights into the mechanisms of RA and tamoxifen-induced TGFβ signaling pathway in breast cancer cells

  20. Proline-linked nitrosoureas as prolidase-convertible prodrugs in human breast cancer cells.

    Science.gov (United States)

    Bielawski, Krzysztof; Bielawska, Anna; Słodownik, Tomasz; Bołkun-Skórnicka, Urszula; Muszyńska, Anna

    2008-01-01

    A number of novel proline-linked nitrosoureas (1-4) were synthesized and examined for cytotoxicity and influence on DNA and collagen biosynthesis in MDA-MB-231 and MCF-7 human breast cancer cells. Evaluation of the cytotoxicity of these compounds employing a MTT assay and inhibition of [(3)H]thymidine incorporation into DNA in both MDA-MB-231 and MCF-7 breast cancer cells demonstrated that compound 2, the most active of the series, proved to be only slightly less potent than carmustine. It has also been found that carmustine did not inhibit MCF&-7 cells prolidase activity, while compounds 1-4 significantly increased its activity, when used at 50-250 microM concentrations. Proline-linked nitrosoureas (1-4) also had lower ability to inhibit collagen biosynthesis in MCF-7 cells, compared to carmustine. The expression of beta(1)-integrin receptor and phosphorylated MAPK, ERK(1) and ERK(2) was significantly decreased in MCF-7 cells incubated for 24 h with 60 microM of compounds 2 and 4 compared to the control, untreated cells, whereas under the same conditions carmustine did not evoke any changes in expression of all these signaling proteins, as shown by Western immunoblot analysis. These results indicate the proline-linked nitrosoureas (1-4), represent multifunctional inhibitors of breast cancer cell growth and metabolism.

  1. Comparison between hemosiderin and Technetium-99 in sentinel lymph node biopsy in human breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Vasques, Paulo Henrique Diogenes; Aquino, Ranniere Gurgel Furtado de; Pinheiro, Luiz Gonzaga Porto, E-mail: luizgporto@uol.com.br [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil). Departamento de Cirurgia; Alves, Mayara Maia [Rede Nordeste de Biotecnologia (RENORBIO/UFC), Fortaleza, CE (Brazil); Torres, Roberto Vitor Almeida; Bezerra, Jose Lucas Martins [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil). Faculdade de Medicina; Brasileiro, Luis Porto [Faculdades INTA, Sobral, CE (Brazil). Faculdade de Medicina

    2015-11-15

    Purpose: To assess the safety and potential equivalence of the use of hemosiderin compared to the Technetium-99 in sentinel lymph node biopsy in human breast cancer. Methods: Non-random sample of 14 volunteer women diagnosed with breast cancer with primary tumors (T1/T2) and clinically tumor-free axilla were submitted to the identification of sentinel lymph node using hemosiderin obtained from autologous blood injected in the periareolar region 24h before surgery on an outpatient basis. Patients received preoperative subareolar intradermal injection of Technetium-99 in the immediate preoperative period. Patients were submitted to sentinel lymph node biopsy, with incision in the axillary fold guided by Gamma-Probe, dissection by planes until the identification of the point of maximum uptake of Technetium-99, identifying the marked nodes and their colors. All surgical specimens were sent for pathological and immunohistochemical study. Results: The results showed no evidence of side effects and/or allergic and non-allergic reactions in patients submitted to SLNB with hemosiderin. The SLN identification rate per patient was 100%. SLNB identification rate per patient with hemosiderin was the same as that of Technetium, with a concordance rate of 100% between the methods. Conclusion: Hemosiderin is a safe dye that is equivalent to Technetium in breast sentinel lymph node biopsy. (author)

  2. Optical redox imaging indices discriminate human breast cancer from normal tissues

    Science.gov (United States)

    Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

    2016-01-01

    Abstract. Our long-term goal was to investigate the potential of incorporating redox imaging technique as a breast cancer (BC) diagnosis component to increase the positive predictive value of suspicious imaging finding and to reduce unnecessary biopsies and overdiagnosis. We previously found that precancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. We also revealed abnormal mitochondrial redox state in cancerous specimens from three BC patients. Here, we extend our study to include biopsies of 16 patients. Tissue aliquots were collected from both apparently normal and cancerous tissues from the affected cancer-bearing breasts shortly after surgical resection. All specimens were snap-frozen and scanned with the Chance redox scanner, i.e., the three-dimensional cryogenic NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins) fluorescence imager. We found both Fp and NADH in the cancerous tissues roughly tripled that in the normal tissues (predox ratio Fp/(NADH + Fp) was ∼27% higher in the cancerous tissues (predox ratio alone could predict cancer with reasonable sensitivity and specificity. Our findings suggest that the optical redox imaging technique can provide parameters independent of clinical factors for discriminating cancer from noncancer breast tissues in human patients. PMID:27896360

  3. Brain metastasis in human epidermal growth factor receptor 2-positive breast cancer: from biology to treatment

    Energy Technology Data Exchange (ETDEWEB)

    Koo, Tae Ryool [Dept. of Radiation Oncology, Hallym University Chuncheon Sacred Heart Hospital, Chuncheon (Korea, Republic of); Kim, In Ah [Dept. of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

    2016-03-15

    Overexpression of human epidermal growth factor receptor 2 (HER2) is found in about 20% of breast cancer patients. With treatment using trastuzumab, an anti-HER2 monoclonal antibody, systemic control is improved. Nonetheless, the incidence of brain metastasis does not be improved, rather seems to be increased in HER2-positive breast cancer. The mainstay treatment for brain metastases is radiotherapy. According to the number of metastatic lesions and performance status of patients, radiosurgery or whole brain radiotherapy can be performed. The concurrent use of a radiosensitizer further improves intracranial control. Due to its large molecular weight, trastuzumab has a limited ability to cross the blood-brain barrier. However, small tyrosine kinase inhibitors such as lapatinib, has been noted to be a promising agent that can be used as a radiosensitizer to affect HER2-positive breast cancer. This review will outline general management of brain metastases and will focus on preclinical findings regarding the radiosensitizing effect of small molecule HER2 targeting agents.

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

    International Nuclear Information System (INIS)

    Li, Yuan-Yuan; Qin, Yi-Zhuo; Wang, Rui-Qi; Li, Wen-Bao; Qu, Xian-Jun

    2013-01-01

    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)

    Bronzert, D.A.; Pantazis, P.; Antoniades, H.N.; Kasid, A.; Davidson, N.; Dickson, R.B.; Lippman, M.E.

    1987-01-01

    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 [ 3 H] 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 (95 0 C) and inhibited by reducing agents. The mitogenic activity comigrates with a material of ≅30 kDa on NaDodSO 4 /polyacrylamide gels. Immunoprecipitation with PDGF antiserum of proteins from metabolically labeled cell lysates and conditioned medium followed by analysis on nonreducing NaDodSO 4 /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. Growth kinetics of four human breast carcinomas grown in nude mice

    DEFF Research Database (Denmark)

    Spang-Thomsen, M; Rygaard, K; Hansen, L

    1989-01-01

    with cell generation times of 42 to 60 hours. The three receptor-positive tumors had slower growth rate, larger tumor volume doubling time, and smaller growth fraction and labelling index than the receptor-negative tumor. However, no single proliferation parameter was sufficient to characterize the growth......The immune-deficient nude mouse with human tumor xenografts is an appropriate model system for performing detailed growth kinetic examinations. In the present study one estrogen and progesterone receptor-negative (T60) and three receptor-positive (Br-10, MCF-7, T61) human breast cancer xenografts...... in nude mice were investigated. The proliferative tumor characteristics were examined by growth curves, thymidine labelling technique, and flow cytometric DNA analysis performed on fine-needle aspirations. The results showed that the tumors had growth kinetics comparable to other human tumor types...

  7. Influence of IFN-gamma and its receptors in human breast cancer

    Directory of Open Access Journals (Sweden)

    Paniagua Ricardo

    2007-08-01

    Full Text Available Abstract Background Interferons are a group of proteins that trigger multiple responses including prevention of viral replication, inhibition of cell growth, and modulation of cell differentiation. In different mammary carcinoma cell lines IFNγ induces growth arrest at mid-G1. At the present there are no in vivo studies in human breast. The aim of this study was to investigate the expression patterns of IFNγ and its two receptors (IFNγ-Rα and IFNγ-Rβ by Western blot and immunohistochemistry, in order to elucidate its role in the different types of human breast cancer (in situ and infiltrative. Methods Immunohistochemical and semiquantitative study of IFNγ, its receptors types (IFNγ-Rα and IFNγ-Rβ, cell proliferation (proliferating cell nuclear antigen, also named PCNA, and apoptosis (TUNEL method was carried between the three breast groups (fibrocystic lesions, in situ tumors and infiltrating tumors. Results In the three groups of patients, IFNγ and IFNγ-Rα immunoreactions appeared in the cytoplasm while IFNγ-Rβ also was found in the nucleus. The optical density to IFNγ was higher in in situ carcinoma than in benign and infiltrating tumors. When we observed IFNγ-Rα, the optical density was lower in infiltrating carcinoma than in benign and in situ tumors (the higher density. To IFNγ-Rβ, the optical density was similar in the three group samples. In tumor samples PCNA and TUNEL index was significantly higher; than in benign diseases. PCNA index increased with the malignance. No significant differences were found between cancer types to TUNEL. IFNγ could be a potential therapeutic tool in breast cancer. However, tumor cells are able to escape from the control of this cytokine in the early tumor stages; this is probably due to a decreased expression of IFNγ, or also to an alteration of either its receptors or some transduction elements. Conclusion We conclude that the decrease in the % positive samples that expressed IFN

  8. A Role for T-Lymphocytes in Human Breast Cancer and in Canine Mammary Tumors

    Directory of Open Access Journals (Sweden)

    Maria Isabel Carvalho

    2014-01-01

    Full Text Available Chronic inflammation in the tumor microenvironment has a prominent role in carcinogenesis and benefits the proliferation and survival of malignant cells, promoting angiogenesis and metastasis. Mammary tumors are frequently infiltrated by a heterogeneous population of immune cells where T-lymphocytes have a great importance. Interestingly, similar inflammatory cell infiltrates, cytokine and chemokine expression in humans and canine mammary tumors were recently described. However, in both species, despite all the scientific evidences that appoint for a significant role of T-lymphocytes, a definitive conclusion concerning the effectiveness of T-cell dependent immune mechanisms has not been achieved yet. In the present review, we describe similarities between human breast cancer and canine mammary tumors regarding tumor T-lymphocyte infiltration, such as relationship of TILs and mammary tumors malignancy, association of ratio CD4+/ CD8+ T-cells with low survival rates, promotion of tumor progression by Th2 cells actions, and association of great amounts of Treg cells with poor prognostic factors. This apparent parallelism together with the fact that dogs develop spontaneous tumors in the context of a natural immune system highlight the dog as a possible useful biological model for studies in human breast cancer immunology.

  9. Distressed or relieved? Psychological side effects of breast cancer screening in the Netherlands

    NARCIS (Netherlands)

    Scaf-Klomp, W; Sanderman, R; van de Wiel, HBM; Otter, R; van den Heuvel, WJA

    1997-01-01

    Study objectives-To assess the psychological impact of mammographic screening on women with non-malignant outcomes after attending the Netherlands' National Breast Cancer Screening Programme. Design-During one year all women with false positive test results (95) in a screening area were invited for

  10. The magnetization transfer characteristics of human breast tissues: an in vitro NMR study

    Science.gov (United States)

    Callicott, C.; Thomas, J. M.; Goode, A. W.

    1999-05-01

    A series of freshly excised human breast tissues was analysed using a nuclear magnetic resonance spectrometer and then subjected to routine histopathology examination. Tissues comprised normal parenchymal, adipose, fibrocystic, fibroadenoma and malignant types. An inversion-recovery sequence performed both with and without magnetization transfer allowed T1, T1, and values to be obtained. From this information, the magnetization transfer rate constant, K, was calculated for each tissue sample. These data show that T1 provided greater discrimination between neoplasic and normal tissues than did T1. However, neither T1 nor K values provided a means of discriminating between benign and malignant disease.

  11. The magnetization transfer characteristics of human breast tissues: an in vitro NMR study

    International Nuclear Information System (INIS)

    Callicott, C.; Thomas, J.M.; Goode, A.W.

    1999-01-01

    A series of freshly excised human breast tissues was analysed using a nuclear magnetic resonance spectrometer and then subjected to routine histopathology examination. Tissues comprised normal parenchymal, adipose, fibrocystic, fibroadenoma and malignant types. An inversion-recovery sequence performed both with and without magnetization transfer allowed T1, T1 5 , M o and M 5 values to be obtained. From this information, the magnetization transfer rate constant, K, was calculated for each tissue sample. These data show that T1 5 provided greater discrimination between neoplasic and normal tissues than did T1. However, neither T1 5 nor K values provided a means of discriminating between benign and malignant disease. (author)

  12. Automated classification of immunostaining patterns in breast tissue from the human protein atlas.

    Science.gov (United States)

    Swamidoss, Issac Niwas; Kårsnäs, Andreas; Uhlmann, Virginie; Ponnusamy, Palanisamy; Kampf, Caroline; Simonsson, Martin; Wählby, Carolina; Strand, Robin

    2013-01-01

    The Human Protein Atlas (HPA) is an effort to map the location of all human proteins (http://www.proteinatlas.org/). It contains a large number of histological images of sections from human tissue. Tissue micro arrays (TMA) are imaged by a slide scanning microscope, and each image represents a thin slice of a tissue core with a dark brown antibody specific stain and a blue counter stain. When generating antibodies for protein profiling of the human proteome, an important step in the quality control is to compare staining patterns of different antibodies directed towards the same protein. This comparison is an ultimate control that the antibody recognizes the right protein. In this paper, we propose and evaluate different approaches for classifying sub-cellular antibody staining patterns in breast tissue samples. The proposed methods include the computation of various features including gray level co-occurrence matrix (GLCM) features, complex wavelet co-occurrence matrix (CWCM) features, and weighted neighbor distance using compound hierarchy of algorithms representing morphology (WND-CHARM)-inspired features. The extracted features are used into two different multivariate classifiers (support vector machine (SVM) and linear discriminant analysis (LDA) classifier). Before extracting features, we use color deconvolution to separate different tissue components, such as the brownly stained positive regions and the blue cellular regions, in the immuno-stained TMA images of breast tissue. We present classification results based on combinations of feature measurements. The proposed complex wavelet features and the WND-CHARM features have accuracy similar to that of a human expert. Both human experts and the proposed automated methods have difficulties discriminating between nuclear and cytoplasmic staining patterns. This is to a large extent due to mixed staining of nucleus and cytoplasm. Methods for quantification of staining patterns in histopathology have many

  13. Automated classification of immunostaining patterns in breast tissue from the human protein Atlas

    Directory of Open Access Journals (Sweden)

    Issac Niwas Swamidoss

    2013-01-01

    Full Text Available Background: The Human Protein Atlas (HPA is an effort to map the location of all human proteins (http://www.proteinatlas.org/. It contains a large number of histological images of sections from human tissue. Tissue micro arrays (TMA are imaged by a slide scanning microscope, and each image represents a thin slice of a tissue core with a dark brown antibody specific stain and a blue counter stain. When generating antibodies for protein profiling of the human proteome, an important step in the quality control is to compare staining patterns of different antibodies directed towards the same protein. This comparison is an ultimate control that the antibody recognizes the right protein. In this paper, we propose and evaluate different approaches for classifying sub-cellular antibody staining patterns in breast tissue samples. Materials and Methods: The proposed methods include the computation of various features including gray level co-occurrence matrix (GLCM features, complex wavelet co-occurrence matrix (CWCM features, and weighted neighbor distance using compound hierarchy of algorithms representing morphology (WND-CHARM-inspired features. The extracted features are used into two different multivariate classifiers (support vector machine (SVM and linear discriminant analysis (LDA classifier. Before extracting features, we use color deconvolution to separate different tissue components, such as the brownly stained positive regions and the blue cellular regions, in the immuno-stained TMA images of breast tissue. Results: We present classification results based on combinations of feature measurements. The proposed complex wavelet features and the WND-CHARM features have accuracy similar to that of a human expert. Conclusions: Both human experts and the proposed automated methods have difficulties discriminating between nuclear and cytoplasmic staining patterns. This is to a large extent due to mixed staining of nucleus and cytoplasm. Methods for

  14. An updated review of worldwide levels of docosahexaenoic and arachidonic acid in human breast milk by region.

    Science.gov (United States)

    Fu, Yuanqing; Liu, Xin; Zhou, Bing; Jiang, Alice C; Chai, Lingying

    2016-10-01

    We aimed to evaluate the DHA and arachidonic acid (AA) levels in human breast milk worldwide by country, region and socio-economic status. Descriptive review conducted on English publications reporting breast-milk DHA and AA levels. We systematically searched and identified eligible literature in PubMed from January 1980 to July 2015. Data on breast-milk DHA and AA levels from women who had given birth to term infants were included. Seventy-eight studies from forty-one countries were included with 4163 breast-milk samples of 3746 individuals. Worldwide mean levels of DHA and AA in breast milk were 0·37 (sd 0·11) % and 0·55 (sd 0·14) % of total fatty acids, respectively. The breast-milk DHA levels from women with accessibility to marine foods were significantly higher than those from women without accessibility (0·35 (sd 0·20) % v. 0·25 (sd 0·14) %, Pworldwide variation in breast-milk DHA and AA levels and underlines the need for future population- or region-specific investigations.

  15. The morphologies of breast cancer cell lines in three-dimensionalassays correlate with their profiles of gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Kenny, Paraic A.; Lee, Genee Y.; Myers, Connie A.; Neve, RichardM.; Semeiks, Jeremy R.; Spellman, Paul T.; Lorenz, Katrin; Lee, Eva H.; Barcellos-Hoff, Mary Helen; Petersen, Ole W.; Gray, Joe W.; Bissell, MinaJ.

    2007-01-31

    3D cell cultures are rapidly becoming the method of choice for the physiologically relevant modeling of many aspects of non-malignant and malignant cell behavior ex vivo. Nevertheless, only a limited number of distinct cell types have been evaluated in this assay to date. Here we report the first large scale comparison of the transcriptional profiles and 3D cell culture phenotypes of a substantial panel of human breast cancer cell lines. Each cell line adopts a colony morphology of one of four main classes in 3D culture. These morphologies reflect, at least in part, the underlying gene expression profile and protein expression patterns of the cell lines, and distinct morphologies were also associated with tumor cell invasiveness and with cell lines originating from metastases. We further demonstrate that consistent differences in genes encoding signal transduction proteins emerge when even tumor cells are cultured in 3D microenvironments.

  16. Intact and cleaved forms of the urokinase receptor enhance discrimination of cancer from non-malignant conditions in patients presenting with symptoms related to colorectal cancer

    DEFF Research Database (Denmark)

    Lomholt, A F; Høyer-Hansen, G; Nielsen, H J

    2009-01-01

    plasminogen activator receptor (suPAR) was proposed as a marker in CRC patients. This study was undertaken to evaluate the individual molecular forms of suPAR as discriminators in a group of patients undergoing endoscopical examination following symptoms related to colorectal cancer. METHODS: In a case......-control study comprising 308 patients undergoing endoscopical examination following CRC-related symptoms, 77 CRC patients with adenocarcinoma were age and gender matched to: 77 patients with adenomas; 77 with other non-malignant findings, and 77 with no findings. The different uPAR forms were measured...

  17. Determining pathogenetic connection between disorders of lipid and carbohydrate metabolism and non-malignant pathology of thyroid gland in children , born from parents, Chernobyl accident survivors

    International Nuclear Information System (INIS)

    Kopilova, O.V.; Stepanenko, O.A.; Belyingyio, T.O.

    2014-01-01

    The 92 children aged 12-17 years were examined with the purpose to study the links between carbohydrate and lipid metabolic abnormalities and non-malignant thyroid disorders in descendants of the Chernobyl accident survivors. Clinical, anthropometrical studies and hormonal assays were applied. Carbohydrate and lipid metabolic abnormalities were revealed in every third case of thyroid disease. It confirms our supposition of such a possibility being due to the fact that radiation impact even in low doses can result in pronounced metabolic disorders lading to entire endocrine disregulation. It is relevant in children of the puberty age

  18. Fucoidan cytotoxicity against human breast cancer T47D cell line increases with higher level of sulfate ester group

    Science.gov (United States)

    Saepudin, Endang; Alfita Qosthalani, Fildzah; Sinurat, Ellya

    2018-01-01

    The anticancer activity of different sulfate ester group content in different molecular weight was examined. The anticancer activity was achieved in vitro on human breast cancer T47D cell line. Fucoidan with lower molecular weight (5.79 kDa) tends to have lower sulfate ester group content (8.69%) and resulted in higher IC50 value (184.22 μg/mL). While fucoidan with higher molecular weight (785.12 kDa) tends to have higher sulfate level (18.63%) and achieved lower IC50 value (75.69 μg/mL). The result showed that in order to maintain fucoidan cytotoxic activity against human breast cancer T47D cell line, the sulfate content should be remain high. Keywords: fucoidan, sulfate ester group, human breast cancer

  19. Epigenetic reversion of breast carcinoma phenotype is accompaniedby DNA sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Sandal, Tone; Valyi-Nagy, Klara; Spencer, Virginia A.; Folberg,Robert; Bissell, Mina J.; Maniotis, Andrew J.

    2006-07-19

    The importance of microenvironment and context in regulation of tissue-specific genes is finally well established. DNA exposure to, or sequestration from, nucleases can be used to detect differences in higher order chromatin structure in intact cells without disturbing cellular or tissue architecture. To investigate the relationship between chromatin organization and tumor phenotype, we utilized an established 3-D assay where normal and malignant human breast cells can be easily distinguished by the morphology of the structures they make (acinus-like vs tumor-like, respectively). We show that these phenotypes can be distinguished also by sensitivity to AluI digestion where the malignant cells are resistant to digestion relative to non-malignant cells. Reversion of the T4-2 breast cancer cells by either cAMP analogs, or a phospatidylinositol 3-kinase (P13K) inhibitor not only reverted the phenotype, but also the chromatin sensitivity to AluI. By using different cAMP-analogs, we show that the cAMP-induced phenotypic reversion, polarization, and shift in DNA organization act through a cAMP-dependent-protein-kinase A-coupled signaling pathway. Importantly, inhibitory antibody to fibronectin also reverted the malignant phenotype, polarized the acini, and changed chromatin sequestration. These experiments show not only that modifying the tumor microenvironment can alter the organization of tumor cells but also that architecture of the tissues and the global chromatin organization are coupled and yet highly plastic.

  20. Breast cancer and human papillomavirus infection: No evidence of HPV etiology of breast cancer in Indian women

    International Nuclear Information System (INIS)

    Hedau, Suresh; Mir, Mohammad Muzaffar; Chakraborty, Sekhar; Singh, Y Mohan; Kumar, Rakesh; Somasundaram, Kumaravel; Bharti, Alok C; Das, Bhudev C; Kumar, Umesh; Hussain, Showket; Shukla, Shirish; Pande, Shailja; Jain, Neeraj; Tyagi, Abhishek; Deshpande, Trivikram; Bhat, Dilafroze

    2011-01-01

    Two clinically relevant high-risk HPV (HR-HPV) types 16 and 18 are etiologically associated with the development of cervical carcinoma and are also reported to be present in many other carcinomas in extra-genital organ sites. Presence of HPV has been reported in breast carcinoma which is the second most common cancer in India and is showing a fast rising trend in urban population. The two early genes E6 and E7 of HPV type 16 have been shown to immortalize breast epithelial cells in vitro, but the role of HPV infection in breast carcinogenesis is highly controversial. Present study has therefore been undertaken to analyze the prevalence of HPV infection in both breast cancer tissues and blood samples from a large number of Indian women with breast cancer from different geographic regions. The presence of all mucosal HPVs and the most common high-risk HPV types 16 and 18 DNA was detected by two different PCR methods - (i) conventional PCR assays using consensus primers (MY09/11, or GP5+/GP6+) or HPV16 E6/E7 primers and (ii) highly sensitive Real-Time PCR. A total of 228 biopsies and corresponding 142 blood samples collected prospectively from 252 patients from four different regions of India with significant socio-cultural, ethnic and demographic variations were tested. All biopsies and blood samples of breast cancer patients tested by PCR methods did not show positivity for HPV DNA sequences in conventional PCRs either by MY09/11 or by GP5+/GP6+/HPV16 E6/E7 primers. Further testing of these samples by real time PCR also failed to detect HPV DNA sequences. Lack of detection of HPV DNA either in the tumor or in the blood DNA of breast cancer patients by both conventional and real time PCR does not support a role of genital HPV in the pathogenesis of breast cancer in Indian women

  1. Method for in-vivo NMR measurements in the human breast to screen for small breast cancer in an otherwise healthy breast

    International Nuclear Information System (INIS)

    Rollwitz, W.L.

    1986-01-01

    A method is described of conducting a noninvasive female breast cancer test comprising the steps of: (a) forming an inhomogeneous magnetic field between the poles of a magnet wherein the magnetic field defines a specific volume between the poles wherein the specific volume has a specified magnetic field intensity H/sub o/ for NMR testing and the specific volume extends outwardly to an edge defined by the outer edge of the female breast; (b) moving incrementally the specific volume from a beginning point toward an ending point to scan a breast between the pole pieces of the magnet and thereby move the specific volume through the breast the movement being with N examinations located along the breast at different locations wherein each specific volume has the defined thickness and outward extent; (c) periodically interrogating by a transmitted pulse from a coil into the breast portion located in the specific volume for NMR response wherein the NMR response is dependent on hydrogen in the water, and the water has two states, one state in cancer cells and the other state in healthy tissue, and the cancer cells provide a different NMR response compared with water in the healthy tissue, the step of interrogating including first and second NMR interrogations of specific breast volumes forming NMR responses; (d) wherein the magnetic field intensity in the specific volume and the pulse from the coil cause an NMR response from water in the body tissue making up the breast portion; and (e) determining cancer cell anomalies arising from cancer cells in the breast as indicated by comparison of the NMR water responses to form difference signals

  2. Oligoadenylate synthetase 1 (OAS1 expression in human breast and prostate cancer cases, and its regulation by sex steroid hormones

    Directory of Open Access Journals (Sweden)

    Cláudio Jorge Maia

    2016-06-01

    Full Text Available Oligoadenylate synthetase 1 (OAS1 is an interferon-induced protein characterised by its capacity to catalyse the synthesis of 2ʹ-5ʹ-linked oligomers of adenosine from adenosine triphosphate (2-5A. The 2-5A binds to a latent Ribonuclease L (RNase L, which subsequently dimerises into its active form and may play an important role in the control of cell growth, differentiation and apoptosis. Previously, our research group identified OAS1 as a differentially-expressed gene in breast and prostate cancer cell lines when compared to normal cells. This study evaluates: i the expression of OAS1 in human breast and prostate cancer specimens; and ii the effect of sex steroid hormones in regulating the expression of OAS1 in breast (MCF-7 and prostate (LNCaP cancer cell lines. The obtained results showed that OAS1 expression was down-regulated in human infiltrative ductal carcinoma of breast, adenocarcinoma of prostate, and benign prostate hyperplasia, both at mRNA and protein level. In addition, OAS1 expression was negatively correlated with the progression of breast and prostate cancer. With regards to the regulation of OAS1 gene, it was demonstrated that 17β-estradiol (E2 down-regulates OAS1 gene in MCF-7 cell lines, an effect that seems to be dependent on the activation of oestrogen receptor (ER. On the other hand, 5α-dihydrotestosterone (DHT treatment showed no effect on the expression of OAS1 in LNCaP cell lines. The lower levels of OAS1 in breast and prostate cancer cases indicated that the OAS1/RNaseL apoptotic pathway may be compromised in breast and prostate tumours. Moreover, the present findings suggested that this effect may be enhanced by oestrogen in ER-positive breast cancers.

  3. Cytoplasmic Skp2 expression is associated with p-Akt1 and predicts poor prognosis in human breast carcinomas.

    Directory of Open Access Journals (Sweden)

    Jing Liu

    Full Text Available BACKGROUND: S-phase kinase protein 2 (Skp2, an oncogenic protein, is a key regulator in different cellular and molecular processes, through ubiquitin-proteasome degradation pathway. Increased levels of Skp2 are observed in various types of cancer and associated with poor prognosis. However, in human breast carcinomas, the underlying mechanism and prognostic significance of cytoplasmic Skp2 is still undefined. METHODS: To investigate the role of cytoplasmic Skp2 expression in human breast carcinomas, we immnohistochemically assessed cytoplasmic Skp2, p-Akt1, and p27 expression in 251 patients with invasive ductal carcinomas of the breast. Association of cytoplasmic Skp2 expression with p-Akt1 and p27 was analyzed as well as correspondence with other clinicopathological parameters. Disease-free survival and overall survival were determined based on the Kaplan-Meier method and Cox regression models. RESULTS: Cytoplasmic of Skp2 was detected in 165 out of 251 (65.7% patients. Cytoplasmic Skp2 expression was associated with larger tumor size, more advanced histological grade, and positive HER2 expression. Increased cytoplasmic Skp2 expression correlated with p-Akt1 expression, with 54.2% (51/94 of low p-Akt1-expressing breast carcinomas, but 72.6% (114/157 of high p-Akt1-expressing breast carcinomas exhibiting cytoplasmic Skp2 expression. Elevated cytoplasmic Skp2 expression with low p-Akt1 expression was associated with poor disease-free and overall survival (DFS and OS, and Cox regression models demonstrated that cytoplasmic Skp2 expression was an independent prognostic marker for invasive breast carcinomas. CONCLUSION: Cytoplasmic Skp2 expression is associated with aggressive prognostic factors, such as larger tumor size, and advanced histological grade of the breast cancers. Results demonstrate that combined cytoplasmic Skp2 and p-Akt1 expression may be prognostic for patients with invasive breast carcinomas, and cytoplasmic Skp2 may serve as a

  4. Tight correlation between expression of the Forkhead transcription factor FOXM1 and HER2 in human breast cancer

    Directory of Open Access Journals (Sweden)

    Hartmann Arndt

    2008-02-01

    Full Text Available Abstract Background FOXM1 regulates expression of cell cycle related genes that are essential for progression into DNA replication and mitosis. Consistent with its role in proliferation, elevated expression of FOXM1 has been reported in a variety of human tumour entities. FOXM1 is a gene of interest because recently chemical inhibitors of FOXM1 were described to limit proliferation and induce apoptosis in cancer cells in vitro, indicating that FOXM1 inhibitors could represent useful anticancer therapeutics. Methods Using immunohistochemistry (IHC we systematically analysed FOXM1 expression in human invasive breast carcinomas (n = 204 and normal breast tissues (n = 46 on a tissue microarray. Additionally, using semiquantitative realtime PCR, a collection of paraffin embedded normal (n = 12 and cancerous (n = 25 breast tissue specimens as well as benign (n = 3 and malignant mammary cell lines (n = 8 were investigated for FOXM1 expression. SPSS version 14.0 was used for statistical analysis. Results FOXM1 was found to be overexpressed in breast cancer in comparison to normal breast tissue both on the RNA and protein level (e.g. 8.7 fold as measured by realtime PCR. We found a significant correlation between FOXM1 expression and the HER2 status determined by HER2 immunohistochemistry (P P = 0.110. Conclusion FOXM1 may represent a novel breast tumour marker with prognostic significance that could be included into multi-marker panels for breast cancer. Interestingly, we found a positive correlation between FOXM1 expression and HER2 status, pointing to a potential role of FOXM1 as a new drug target in HER2 resistant breast tumour, as FOXM1 inhibitors for cancer treatment were described recently. Further studies are underway to analyse the potential interaction between FOXM1 and HER2, especially whether FOXM1 directly activates the HER2 promoter.

  5. The anticancer potential of steroidal saponin, dioscin, isolated from wild yam (Dioscorea villosa) root extract in invasive human breast cancer cell line MDA-MB-231 in vitro

    Science.gov (United States)

    Previously, we observed that wild yam (Dioscorea villosa) root extract (WYRE) was able to activate GATA3 in human breast cancer cells targeting epigenome. This study aimed to 'nd out if dioscin (DS), a bioactive compound of WYRE, can modulate GATA3 functions and cellular invasion in human breast can...

  6. Loss of heterozygosity on the X chromosome in human breast cancer.

    Science.gov (United States)

    Loupart, M L; Adams, S; Armour, J A; Walker, R; Brammar, W; Varley, J

    1995-08-01

    The analysis of loss of heterozygosity (LOH) in tumours can be a powerful tool for mapping the sites of tumour suppressor genes in the human genome. A panel of breast cancer patients was assembled as pairs of tumour and lymphocyte DNA samples and LOH studies carried out by Southern hybridisation with polymorphic loci mapping to the X chromosome with appropriate controls. Deletion mapping revealed a high frequency of small regionalised deletions, defining at least three independent regions, one of which is particularly well mapped to a 500 kb stretch of DNA in the distal portion of the pseudoautosomal region of Xp. A second region has been identified within the pseudoautosomal region close to the pseudoautosomal boundary, and there is a third discrete site of loss on distal Xq. Perturbations of sequences at these regions represent independent events in a number of patients. This study represents the first detailed analysis of LOH on the X chromosome in human breast tumours, the results of which indicate that at least three regions of this chromosome are involved in the disease.

  7. Biocatalytically Oligomerized Epicatechin with Potent and Specific Anti-proliferative Activity for Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ramaswamy Nagarajan

    2008-11-01

    Full Text Available Catechins, naturally occurring flavonoids derived from wine and green tea, are known to exhibit multiple health benefits. Epigallocatechin gallate (EGCG is one of the most widely investigated catechins, but its efficacy in cancer therapy is still inconsistent and limited. The poor stability of EGCG has contributed to the disparity in the reported anti-cancer activity and other beneficial properties. Here we report an innovative enzymatic strategy for the oligomerization of catechins (specifically epicatechin that yields stable, water-soluble oligomerized epicatechins with enhanced and highly specific anti-proliferative activity for human breast cancer cells. This one-pot oxidative oligomerization is carried out in ambient conditions using Horseradish Peroxidase (HRP as a catalyst yielding water-soluble oligo(epicatechins. The oligomerized epicatechins obtained exhibit excellent growth inhibitory effects against human breast cancer cells with greater specificity towards growth-inhibiting cancer cells as opposed to normal cells, achieving a high therapeutic differential. Our studies indicate that water-soluble oligomeric epicatechins surpass EGCG in stability, selectivity and efficacy at lower doses.

  8. Apoptotic effect of chalcone derivatives of 2-acetylthiophene in human breast cancer cells.

    Science.gov (United States)

    Fogaça, Tatiana B; Martins, Rosiane M; Begnini, Karine R; Carapina, Caroline; Ritter, Marina; de Pereira, Claudio M P; Seixas, Fabiana K; Collares, Tiago

    2017-02-01

    A variety of chalcones have demonstrated cytotoxic activity toward several cancer cell lines. This study aimed to investigate the cytotoxicity of four chalcones derivatives of 2-acetylthiophene in human breast cancer cell lines. MCF-7 and MDA-MB-231 cells were treated with synthesized chalcones and the cytotoxicity was evaluated by tetrazolium dye (MTT), live/dead, and DAPI assays. Chalcones significantly decreased MCF-7 and MDA-MB-231 cells viability in vitro in a dose dependent manner. After 48h treatment, the IC 50 values ranging from 5.52 to 34.23μM. Chalcone 3c displayed the highest cytotoxic activity from all the tested compounds. Cytotoxic effects of compounds were confirmed in the live/dead assay. In addition, DAPI staining revealed that these compounds induce death by apoptosis. The data speculate that chalcone derivatives of 2-acetylthiophene may represent a source of therapeutic agents for human breast cancer. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  9. Expression of neurotensin and NT1 receptor in human breast cancer: a potential role in tumor progression.

    Science.gov (United States)

    Souazé, Frédérique; Dupouy, Sandra; Viardot-Foucault, Véronique; Bruyneel, Erik; Attoub, Samir; Gespach, Christian; Gompel, Anne; Forgez, Patricia

    2006-06-15

    Emerging evidence supports neurotensin as a trophic and antiapoptotic factor, mediating its control via the high-affinity neurotensin receptor (NT1 receptor) in several human solid tumors. In a series of 51 patients with invasive ductal breast cancers, 34% of all tumors were positive for neurotensin and 91% positive for NT1 receptor. We found a coexpression of neurotensin and NT1 receptor in a large proportion (30%) of ductal breast tumors, suggesting a contribution of the neurotensinergic signaling cascade within breast cancer progression. Functionally expressed NT1 receptor, in the highly malignant MDA-MB-231 human breast cancer cell line, coordinated a series of transforming functions, including cellular migration, invasion, induction of the matrix metalloproteinase (MMP)-9 transcripts, and MMP-9 gelatinase activity. Disruption of NT1 receptor signaling by silencing RNA or use of a specific NT1 receptor antagonist, SR48692, caused the reversion of these transforming functions and tumor growth of MDA-MB-231 cells xenografted in nude mice. Our findings support the contribution of neurotensin in human breast cancer progression and point out the utility to develop therapeutic molecules targeting neurotensin or NT1 receptor signaling cascade. These strategies would increase the range of therapeutic approaches and be beneficial for specific patients.

  10. Up-regulation of METCAM/MUC18 promotes motility, invasion, and tumorigenesis of human breast cancer cells

    International Nuclear Information System (INIS)

    Zeng, Guo-fang; Cai, Shao-xi; Wu, Guang-Jer

    2011-01-01

    Conflicting research has identified METCAM/MUC18, an integral membrane cell adhesion molecule (CAM) in the Ig-like gene super-family, as both a tumor promoter and a tumor suppressor in the development of breast cancer. To resolve this, we have re-investigated the role of this CAM in the progression of human breast cancer cells. Three breast cancer cell lines were used for the tests: one luminal-like breast cancer cell line, MCF7, which did not express any METCAM/MUC18, and two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which expressed moderate levels of the protein. MCF7 cells were transfected with the human METCAM/MUC18 cDNA to obtain G418-resistant clones which expressed the protein and were used for testing effects of human METCAM/MUC18 expression on in vitro motility and invasiveness, and in vitro and in vivo tumorigenesis. Both MDA-MB-231 and MDA-MB-468 cells already expressed METCAM/MUC18. They were directly used for in vitro tests in the presence and absence of an anti-METCAM/MUC18 antibody. In MCF7 cells, enforced METCAM/MUC18 expression increased in vitro motility, invasiveness, anchorage-independent colony formation (in vitro tumorigenesis), and in vivo tumorigenesis. In both MDA-MB-231 and MDA-MB-468 cells, the anti-METCAM/MUC18 antibody inhibited both motility and invasiveness. Though both MDA-MB-231 and MDA-MB-468 cells established a disorganized growth in 3D basement membrane culture assay, the introduction of the anti-METCAM/MUC18 antibody completely destroyed their growth in the 3D culture. These findings support the notion that human METCAM/MUC18 expression promotes the progression of human breast cancer cells by increasing their motility, invasiveness and tumorigenesis

  11. Up-regulation of METCAM/MUC18 promotes motility, invasion, and tumorigenesis of human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Cai Shao-xi

    2011-03-01

    Full Text Available Abstract Background Conflicting research has identified METCAM/MUC18, an integral membrane cell adhesion molecule (CAM in the Ig-like gene super-family, as both a tumor promoter and a tumor suppressor in the development of breast cancer. To resolve this, we have re-investigated the role of this CAM in the progression of human breast cancer cells. Methods Three breast cancer cell lines were used for the tests: one luminal-like breast cancer cell line, MCF7, which did not express any METCAM/MUC18, and two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which expressed moderate levels of the protein. MCF7 cells were transfected with the human METCAM/MUC18 cDNA to obtain G418-resistant clones which expressed the protein and were used for testing effects of human METCAM/MUC18 expression on in vitro motility and invasiveness, and in vitro and in vivo tumorigenesis. Both MDA-MB-231 and MDA-MB-468 cells already expressed METCAM/MUC18. They were directly used for in vitro tests in the presence and absence of an anti-METCAM/MUC18 antibody. Results In MCF7 cells, enforced METCAM/MUC18 expression increased in vitro motility, invasiveness, anchorage-independent colony formation (in vitro tumorigenesis, and in vivo tumorigenesis. In both MDA-MB-231 and MDA-MB-468 cells, the anti-METCAM/MUC18 antibody inhibited both motility and invasiveness. Though both MDA-MB-231 and MDA-MB-468 cells established a disorganized growth in 3D basement membrane culture assay, the introduction of the anti-METCAM/MUC18 antibody completely destroyed their growth in the 3D culture. Conclusion These findings support the notion that human METCAM/MUC18 expression promotes the progression of human breast cancer cells by increasing their motility, invasiveness and tumorigenesis.

  12. Promoter methylation-associated loss of ID4 expression is a marker of tumour recurrence in human breast cancer

    International Nuclear Information System (INIS)

    Noetzel, Erik; Veeck, Jürgen; Niederacher, Dieter; Galm, Oliver; Horn, Felicitas; Hartmann, Arndt; Knüchel, Ruth; Dahl, Edgar

    2008-01-01

    Inhibitor of DNA binding/Inhibitor of differentiation 4 (ID4) is a critical factor for cell proliferation and differentiation in normal vertebrate development. ID4 has regulative functions for differentiation and growth of the developing brain. The role of ID1, ID2 and ID3 are expected to be oncogenic due to their overexpression in pancreatic cancer and colorectal adenocarcinomas, respectively. Aside from these findings, loss of ID3 expression was demonstrated in ovarian cancer. The aim of the present study was to reveal the factual role of ID4 in carcinogenesis in more detail, since its role for the pathogenesis of human breast cancer has been discussed controversially, assigning both oncogenic and tumour suppressive functions. ID4 promoter methylation, ID4 mRNA expression and ID4 protein expression were analysed in primary human breast cancer specimens using methylation-specific PCR (MSP) (n=170), semiquantitative realtime RT-PCR (n=46) and immunhistochemistry (n=3), respectively. In order to demonstrate a functional association of ID4 promoter methylation with its gene silencing, we performed DNA demethylation analysis with four human breast cell lines using MSP and semiquantitative realtime RT-PCR. In addition, we performed correlations of ID4 promoter methylation with ID4 mRNA and ID4 protein expression in matched samples of breast tumour and corresponding normal tissue. We carried out statistical analyses in order to find correlations between ID4 promoter methylation and clinicopathological parameters. Frequent ID4 promoter methylation was observed in primary breast cancer samples (69%, 117/170). We found a tight correlation (P<0.0001) between ID4 promoter methylation and loss of ID4 expression in primary breast cancer 3 specimens. Demethylating treatment with breast cancer cell lines was associated with clear ID4 mRNA re-expression. Tumours with ID4 promoter methylation showed distinct loss of ID4 expression on both transcription and protein level

  13. EP4 as a Therapeutic Target for Aggressive Human Breast Cancer

    Directory of Open Access Journals (Sweden)

    Mousumi Majumder

    2018-03-01

    selective EP4 antagonists (EP4A could mitigate all of these events tested with cells in vitro as well as in vivo in syngeneic COX-2 expressing mammary cancer bearing mice or immune-deficient mice bearing COX-2 over-expressing human breast cancer xenografts. We suggest that EP4A can avoid thrombo-embolic side effects of long term use of COX-2 inhibitors by sparing cardio-protective roles of PGI2 via IP receptor activation or PGE2 via EP3 receptor activation. Furthermore, we identified two COX-2/EP4 induced oncogenic and SLC-stimulating microRNAs—miR526b and miR655, one of which (miR655 appears to be a potential blood biomarker in breast cancer patients for monitoring SLC-ablative therapies, such as with EP4A. We suggest that EP4A will likely produce the highest benefit in aggressive breast cancers, such as COX-2 expressing triple-negative breast cancers, when combined with other newer agents, such as inhibitors of programmed cell death (PD-1 or PD-L1.

  14. Aluminium, carbonyls and cytokines in human nipple aspirate fluids: Possible relationship between inflammation, oxidative stress and breast cancer microenvironment.

    Science.gov (United States)

    Mannello, F; Ligi, D; Canale, M

    2013-11-01

    The human breast is likely exposed to Al (aluminium) from many sources including diet and personal care products. Underarm applications of aluminium salt-based antiperspirant provide a possible long-term source of exposure, especially after underarm applications to shaved and abraded skin. Al research in breast fluids likely reflects the intraductal microenvironment. We found increased levels of aluminium in noninvasively collected nipple aspirate fluids (NAF) from 19 breast cancer patients compared with 16 healthy control subjects (268 vs 131 μg/l, respectively; p Aluminium content and carbonyl levels showed a significant positive linear correlation (r(2) 0.6628, p aluminium salts) we also found a significantly increased levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-12 p70, and TNF-α) and chemoattractant CC and CXC chemokines (IL-8, MIP-1α and MCP-1). In 12 invasive cancer NAF samples we found a significant positive linear correlation among aluminium, carbonyls and pro-inflammatory IL-6 cytokine (Y = 64.79x-39.63, r(2) 0.8192, p aluminium ions in oxidative and inflammatory status perturbations of breast cancer microenvironment, suggesting aluminium accumulation in breast microenvironment as a possible risk factor for oxidative/inflammatory phenotype of breast cells. © 2013.

  15. Dioxins, PCBs and organochlorine pesticides in human breast milk from Malaysia

    Energy Technology Data Exchange (ETDEWEB)

    Sudaryanto, A.; Kunisue, T.; Iwata, H.; Tanabe, S. [Center for Marine Environmental Studies, Ehime Univ., Matsuyama (Japan); Niida, M. [Japan Offspring Fund, Tokyo (Japan); Hashim, H. [Consumers Association of Penang, Pulau Pinang (Malaysia)

    2004-09-15

    Contaminations by persistent organic pollutants (POPs) such as polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs) and organochlorine pesticides in the environment have been of great concern due to their endocrine disrupting effects on humans and wildlife. Chemically stable and lipophilic properties of these contaminants led to their high contamination in higher trophic biota, including human. Despite the intensive monitoring efforts and anticipated results of decreasing trends of POPs in developed countries as a consequence of their regulation on use and waste treatment, little information are available on their contamination status in developing countries even though these chemicals are still being used and unintentionally produced in several parts of these countries. To ensure the reliability of exposure data and to delineate contamination status, fate and behavior in tropical developing countries, during last few years, our research groups conducted monitoring studies using various environmental matrices including air, water, sediment, soil, biota and human from several Asian developing countries. From these results, existing sources of OCs and formation of dioxins and related compounds could be predicted in this region. However, there is very little information addressing the accumulation of OCs pollution in Malaysia. Particularly available data are only on marine biota. To date no data are available on OCs contaminations in human milk samples from Malaysia. The present study aims at understanding recent contamination of POPs, including dioxins and related compounds, PCBs and OCs pesticides in human breast milk from the general population of Malaysia.

  16. Epigenome remodelling in breast cancer: insights from an early in vitro model of carcinogenesis.

    Science.gov (United States)

    Locke, Warwick J; Clark, Susan J

    2012-11-15

    Epigenetic gene regulation has influence over a diverse range of cellular functions, including the maintenance of pluripotency, differentiation, and cellular identity, and is deregulated in many diseases, including cancer. Whereas the involvement of epigenetic dysregulation in cancer is well documented, much of the mechanistic detail involved in triggering these changes remains unclear. In the current age of genomics, the development of new sequencing technologies has seen an influx of genomic and epigenomic data and drastic improvements in both resolution and coverage. Studies in cancer cell lines and clinical samples using next-generation sequencing are rapidly delivering spectacular insights into the nature of the cancer genome and epigenome. Despite these improvements in technology, the timing and relationship between genetic and epigenetic changes that occur during the process of carcinogenesis are still unclear. In particular, what changes to the epigenome are playing a driving role during carcinogenesis and what influence the temporal nature of these changes has on cancer progression are not known. Understanding the early epigenetic changes driving breast cancer has the exciting potential to provide a novel set of therapeutic targets or early-disease biomarkers or both. Therefore, it is important to find novel systems that permit the study of initial epigenetic events that potentially occur during the first stages of breast cancer. Non-malignant human mammary epithelial cells (HMECs) provide an exciting in vitro model of very early breast carcinogenesis. When grown in culture, HMECs are able to temporarily escape senescence and acquire a pre-malignant breast cancer-like phenotype (variant HMECs, or vHMECs). Cultured HMECs are composed mainly of cells from the basal breast epithelial layer. Therefore, vHMECs are considered to represent the basal-like subtype of breast cancer. The transition from HMECs to vHMECs in culture recapitulates the epigenomic

  17. Targeting human breast cancer cells by an oncolytic adenovirus using microRNA-targeting strategy.

    Science.gov (United States)

    Shayestehpour, Mohammad; Moghim, Sharareh; Salimi, Vahid; Jalilvand, Somayeh; Yavarian, Jila; Romani, Bizhan; Mokhtari-Azad, Talat

    2017-08-15

    MicroRNA-targeting strategy is a promising approach that enables oncolytic viruses to replicate in tumor cells but not in normal cells. In this study, we targeted adenoviral replication toward breast cancer cells by inserting ten complementary binding sites for miR-145-5p downstream of E1A gene. In addition, we evaluated the effect of increasing miR-145 binding sites on inhibition of virus replication. Ad5-control and adenoviruses carrying five or ten copies of miR145-5p target sites (Ad5-5miR145T, Ad5-10miR145T) were generated and inoculated into MDA-MB-453, BT-20, MCF-7 breast cancer cell lines and human mammary epithelial cells (HMEpC). Titer of Ad5-10miR145T in HMEpC was significantly lower than Ad5-control titer. Difference between the titer of these two viruses at 12, 24, 36, and 48h after infection was 1.25, 2.96, 3.06, and 3.77 log TCID 50 . No significant difference was observed between the titer of both adenoviruses in MDA-MB-453, BT-20 and MCF-7 cells. The infectious titer of adenovirus containing 10 miR-145 binding sites in HMEpC cells at 24, 36, and 48h post-infection was 1.7, 2.08, and 4-fold, respectively, lower than the titer of adenovirus carrying 5 miR-145 targets. Our results suggest that miR-145-targeting strategy provides selectivity for adenovirus replication in breast cancer cells. Increasing the number of miRNA binding sites within the adenoviral genome confers more selectivity for viral replication in cancer cells. Copyright © 2017. Published by Elsevier B.V.

  18. Cadmium telluride quantum dots induce apoptosis in human breast cancer cell lines.

    Science.gov (United States)

    Naderi, Saeed; Zare, Hakimeh; Taghavinia, Nima; Irajizad, Azam; Aghaei, Mahmoud; Panjehpour, Mojtaba

    2018-05-01

    Semiconductor quantum dots (QDs), especially those containing cadmium, have undergone marked improvements and are now widely used nanomaterials in applicable biological fields. However, great concerns exist regarding their toxicity in biomedical applications. Because of the lack of sufficient data regarding the toxicity mechanism of QDs, this study aimed to evaluate the cytotoxicity of three types of QDs: CdTe QDs, high yield CdTe QDs, and CdTe/CdS core/shell QDs on two human breast cancer cell lines MDA-MB468 and MCF-7. The breast cancer cells were treated with different concentrations of QDs, and cell viability was evaluated via MTT assay. Hoechst staining was applied for observation of morphological changes due to apoptosis. Apoptotic DNA fragmentation was visualized by the agarose gel electrophoresis assay. Flow cytometric annexin V/propidium iodide (PI) measurement was used for apoptosis detection. A significant decrease in cell viability was observed after QDs treatment ( p < 0.05). Apoptotic bodies and chromatin condensation was observed by Hoechst staining. DNA fragmentation assay demonstrated a DNA ladder profile in the exposed cells and also annexin V/PI flow cytometry confirmed apoptosis in a dose-dependent manner. Our results revealed that CdTe, high yield CdTe, and CdTe/CdS core/shell QDs induce apoptosis in breast cancer cell lines in a dose-dependent manner. This study would help realizing the underlying cytotoxicity mechanism, at least partly, of CdTe QDs and may provide information for the development of nanotoxicology and safe use of biological applications of QDs.

  19. Mutant p53 protein in serum could be used as a molecular marker in human breast cancer.

    Science.gov (United States)

    Balogh, G A; Mailo, D A; Corte, M M; Roncoroni, P; Nardi, H; Vincent, E; Martinez, D; Cafasso, M E; Frizza, A; Ponce, G; Vincent, E; Barutta, E; Lizarraga, P; Lizarraga, G; Monti, C; Paolillo, E; Vincent, R; Quatroquio, R; Grimi, C; Maturi, H; Aimale, M; Spinsanti, C; Montero, H; Santiago, J; Shulman, L; Rivadulla, M; Machiavelli, M; Salum, G; Cuevas, M A; Picolini, J; Gentili, A; Gentili, R; Mordoh, J

    2006-04-01

    p53 wild-type is a tumor suppressor gene involved in DNA gene transcription or DNA repair mechanisms. When damage to DNA is unrepairable, p53 induces programmed cell death (apoptosis). The mutant p53 gene is the most frequent molecular alteration in human cancer, including breast cancer. Here, we analyzed the genetic alterations in p53 oncogene expression in 55 patients with breast cancer at different stages and in 8 normal women. We measured by ELISA assay the serum levels of p53 mutant protein and p53 antibodies. Immunohistochemistry and RT-PCR using specific p53 primers as well as mutation detection by DNA sequencing were also evaluated in breast tumor tissue. Serological p53 antibody analysis detected 0/8 (0%), 0/4 (0%) and 9/55 (16.36%) positive cases in normal women, in patients with benign breast disease and in breast carcinoma, respectively. We found positive p53 mutant in the sera of 0/8 (0.0%) normal women, 0/4 (0%) with benign breast disease and 29/55 (52.72%) with breast carcinoma. Immunohistochemistry evaluation was positive in 29/55 (52.73%) with mammary carcinoma and 0/4 (0%) with benign breast disease. A very good correlation between p53 mutant protein detected in serum and p53 accumulation by immunohistochemistry (83.3% positive in both assays) was found in this study. These data suggest that detection of mutated p53 could be a useful serological marker for diagnostic purposes.

  20. Effects of hydroxyapatite nanoparticles on proliferation and apoptosis of human breast cancer cells (MCF-7)

    International Nuclear Information System (INIS)

    Meena, Ramovatar; Kesari, Kavindra Kumar; Rani, Madhu; Paulraj, R.

    2012-01-01

    The study aimed to correlate cell proliferation inhibition with oxidative stress and p53 protein expression in cancerous cells. Hydroxyapatite (HAP) (Ca 10 (PO 4 ) 6 (OH) 2 ) is the essential component of inorganic composition in human bone. It has been found to have obvious inhibitory function on growth of many kinds of tumor cells and its nanoparticle has stronger anti-cancerous effect than macromolecule microparticles. Human breast cancer cells (MCF-7) were cultured and treated with HAP nanoparticles at various concentrations. Cells viability was detected with MTT colorimetric assay. The morphology of the cancerous cells was performed by transmission electron microscopy and the expression of a cell apoptosis related gene (p53) was determined by ELISA assay and flow cytometry (FCM). The intracellular reactive oxygen species (ROS) level in HAP exposed cells was measured by H 2 DCFDA staining. DNA damage was measured by single-cell gel electrophoresis assay. The statistical analysis was done by one way ANOVA. The cellular proliferation inhibition rate was significantly (p < 0.05) increasing in a dose-dependent manner of HAP nanoparticles. Cell apoptotic characters were observed after MCF-7 cells were treated by HAP nanoparticles for 48 h. Moreover, ELISA assay and FCM shows a dose-dependent activation of p53 in MCF-7 cells treated with nanoHAP. These causative factors of the above results may be justified by an overproduction of ROS. In this study, a significant (p < 0.05) increase in the level of intracellular ROS in HAP-treated cells was observed. This study shows that HAP inhibits the growth of human breast cancer MCF-7 cells as well as induces cell apoptosis. This study shows that HAP NPs Induce the production of intracellular reactive oxygen species and activate p53, which may be responsible for DNA damage and cell apoptosis.

  1. Antitumor activity of Bulgarian herb Tribulus terrestris L. on human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Svetla Angelova

    2013-01-01

    Full Text Available Medicinal plants have been intensively studied as a source of antitumor compounds. Due to the beneficial climate conditions Bulgarian herbs have high pharmacological potential. Currently, the antitumor effect of the Bulgarian medicinal plant Tribulus terrestris L. on human cancer cell lines is not studied. The main active compounds of the plant are the steroid saponins.The present study aims to analyze the effect on cell viability and apoptotic activity of total extract and saponin fraction of Bulgarian Tribulus terrestris L. on human breast cancer (MCF7 and normal (MCF10A cell lines. Antitumor effect was established by МТТ cell viability assay and assessment of apoptotic potential was done through analysis of genomic integrity (DNA fragmentation assay and analysis of morphological cell changes (Fluorescence microscopy. The results showed that total extract of the herb has a marked dose-dependent inhibitory effect on viability of MCF7 cells (half maximal inhibitory concentration is 15 μg/ml. Cell viability of MCF10A was moderately decreased without visible dose-dependent effect. The saponin fraction has increased inhibitory effect on breast cancer cells compared to total extract. Morphological changes and DNA fragmentation were observed as markers for early and late apoptosis predominantly in tumor cells after treatment. Apoptotic processes were intensified with the increase of treatment duration.The obtained results are the first showing selective antitumor activity of Bulgarian Tribulus terrestris L. on human cancer cells in vitro. Apoptotic processes are involved in the antitumor mechanisms induced by the herb. This results give directions for future investigations concerning detailed assessment of its pharmacological potential.

  2. In search of a stem cell hierarchy in the human breast and its relevance to breast cancer evolution

    DEFF Research Database (Denmark)

    Villadsen, René

    2005-01-01

    . Most attention has been devoted to the question of different cellular origins of cancer subtypes and different susceptibilities of possible stem cells to gain or loss of oncogenes and tumor suppressor genes, respectively. Invaluable progress has been made over the past two decades in culture technology......, kidney and prostate. It is therefore now possible to integrate this information in a search for similar cells within the breast. Even if cell turnover after birth is provided exclusively by dividing lineage-restricted cells, more information about the robustness of breast differentiation programs during...

  3. Breast cancer and human papillomavirus infection: No evidence of HPV etiology of breast cancer in Indian women

    Directory of Open Access Journals (Sweden)

    Singh Y Mohan

    2011-01-01

    Full Text Available Abstract Background Two clinically relevant high-risk HPV (HR-HPV types 16 and 18 are etiologically associated with the development of cervical carcinoma and are also reported to be present in many other carcinomas in extra-genital organ sites. Presence of HPV has been reported in breast carcinoma which is the second most common cancer in India and is showing a fast rising trend in urban population. The two early genes E6 and E7 of HPV type 16 have been shown to immortalize breast epithelial cells in vitro, but the role of HPV infection in breast carcinogenesis is highly controversial. Present study has therefore been undertaken to analyze the prevalence of HPV infection in both breast cancer tissues and blood samples from a large number of Indian women with breast cancer from different geographic regions. Methods The presence of all mucosal HPVs and the most common high-risk HPV types 16 and 18 DNA was detected by two different PCR methods - (i conventional PCR assays using consensus primers (MY09/11, or GP5+/GP6+ or HPV16 E6/E7 primers and (ii highly sensitive Real-Time PCR. A total of 228 biopsies and corresponding 142 blood samples collected prospectively from 252 patients from four different regions of India with significant socio-cultural, ethnic and demographic variations were tested. Results All biopsies and blood samples of breast cancer patients tested by PCR methods did not show positivity for HPV DNA sequences in conventional PCRs either by MY09/11 or by GP5+/GP6+/HPV16 E6/E7 primers. Further testing of these samples by real time PCR also failed to detect HPV DNA sequences. Conclusions Lack of detection of HPV DNA either in the tumor or in the blood DNA of breast cancer patients by both conventional and real time PCR does not support a role of genital HPV in the pathogenesis of breast cancer in Indian women.

  4. Expression of Prostacyclin-Synthase in Human Breast Cancer: Negative Prognostic Factor and Protection against Cell Death In Vitro

    Directory of Open Access Journals (Sweden)

    Thomas Klein

    2015-01-01

    Full Text Available Endogenously formed prostacyclin (PGI2 and synthetic PGI2 analogues have recently been shown to regulate cell survival in various cell lines. To elucidate the significance of PGI2 in human breast cancer, we performed immunohistochemistry to analyze expression of prostacyclin-synthase (PGIS in 248 human breast cancer specimens obtained from surgical pathology files. We examined patients’ 10-year survival retrospectively by sending a questionnaire to their general practitioners and performed univariate analysis to determine whether PGIS expression correlated with patient survival. Lastly, the effects of PGI2 and its analogues on cell death were examined in a human breast cancer cell line (MCF-7 and a human T-cell leukemia cell line (CCRF-CEM. PGIS expression was observed in tumor cells in 48.7% of samples and was associated with a statistically significant reduction in 10-year survival (P=0.038; n=193. Transient transfection of PGIS into MCF-7 cells exposed to sulindac increased cell viability by 50% and exposure to carbaprostacyclin protected against sulindac sulfone induced apoptosis in CCRF-CEM cells. Expression of PGIS is correlated with a reduced patient survival and protects against cell death in vitro, suggesting that PGIS is a potential therapeutic target in breast cancer.

  5. The breast cancer resistance protein transporter ABCG2 is expressed in the human kidney proximal tubule apical membrane.

    NARCIS (Netherlands)

    Huls, M.; Brown, C.D.; Windass, A.S.; Sayer, R.; Heuvel, J.J.M.W. van den; Heemskerk, S.; Russel, F.G.M.; Masereeuw, R.

    2008-01-01

    The Breast Cancer Resistance Protein (BCRP/ABCG2) is a transporter restricting absorption and enhancing excretion of many compounds including anticancer drugs. This transporter is highly expressed in many tissues; however, in human kidney, only the mRNA was found in contrast to the mouse kidney,

  6. Characterizing Spatial Organization of Cell Surface Receptors in Human Breast Cancer with STORM

    Science.gov (United States)

    Lyall, Evan; Chapman, Matthew R.; Sohn, Lydia L.

    2012-02-01

    Regulation and control of complex biological functions are dependent upon spatial organization of biological structures at many different length scales. For instance Eph receptors and their ephrin ligands bind when opposing cells come into contact during development, resulting in spatial organizational changes on the nanometer scale that lead to changes on the macro scale, in a process known as organ morphogenesis. One technique able to probe this important spatial organization at both the nanometer and micrometer length scales, including at cell-cell junctions, is stochastic optical reconstruction microscopy (STORM). STORM is a technique that localizes individual fluorophores based on the centroids of their point spread functions and then reconstructs a composite image to produce super resolved structure. We have applied STORM to study spatial organization of the cell surface of human breast cancer cells, specifically the organization of tyrosine kinase receptors and chemokine receptors. A better characterization of spatial organization of breast cancer cell surface proteins is necessary to fully understand the tumorigenisis pathways in the most common malignancy in United States women.

  7. 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.

  8. Bacterial invasion of HT29-MTX-E12 monolayers: effects of human breast milk.

    Science.gov (United States)

    Hall, Tim; Dymock, David; Corfield, Anthony P; Weaver, Gillian; Woodward, Mark; Berry, Monica

    2013-02-01

    The supramucosal gel, crucial for gut barrier function, might be compromised in necrotizing enterocolitis (NEC). Breast milk is associated with a reduced incidence of NEC. We compared the effects of human breast milk (BM) versus a neonatal formula, Nutriprem 1 (FF), on adherence, internalisation, and penetration of NEC-associated Escherichia coli through monolayers of mucus producing intestinal cells, HT29-MTX-E12 (E12). E12 cells were grown to confluence on membranes permeable to bacteria. E. coli, reference strain and isolated from a NEC-affected intestine, were cultured in LB broth, labelled with fluorescein and biotinylated. Bacteria were suspended in tissue culture medium (TC) or mixtures of TC with BM or FF and applied to the E12 cultures. Bacterial numbers were assessed by fluorescence. DyLight 650-labelled neutravidin, which cannot cross cell membrane, evaluated extracellular bacteria. Fluorescence of basolateral medium was measured to quantify translocation. Bacterial concentrations were compared using the Mann Whitney U test. After 1h exposure, E12 cultures adhered or internalised more NEC-derived bacteria than standard strain E. coli and more suspended in FF than BM (Pmilk was associated with relatively less adhesion and internalisation of NEC-associated E. coli to mucus covered E12s compared to formula milk. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Processed images in human perception: A case study in ultrasound breast imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yap, Moi Hoon [Department of Computer Science, Loughborough University, FH09, Ergonomics and Safety Research Institute, Holywell Park (United Kingdom)], E-mail: M.H.Yap@lboro.ac.uk; Edirisinghe, Eran [Department of Computer Science, Loughborough University, FJ.05, Garendon Wing, Holywell Park, Loughborough LE11 3TU (United Kingdom); Bez, Helmut [Department of Computer Science, Loughborough University, Room N.2.26, Haslegrave Building, Loughborough University, Loughborough LE11 3TU (United Kingdom)

    2010-03-15

    Two main research efforts in early detection of breast cancer include the development of software tools to assist radiologists in identifying abnormalities and the development of training tools to enhance their skills. Medical image analysis systems, widely known as Computer-Aided Diagnosis (CADx) systems, play an important role in this respect. Often it is important to determine whether there is a benefit in including computer-processed images in the development of such software tools. In this paper, we investigate the effects of computer-processed images in improving human performance in ultrasound breast cancer detection (a perceptual task) and classification (a cognitive task). A survey was conducted on a group of expert radiologists and a group of non-radiologists. In our experiments, random test images from a large database of ultrasound images were presented to subjects. In order to gather appropriate formal feedback, questionnaires were prepared to comment on random selections of original images only, and on image pairs consisting of original images displayed alongside computer-processed images. We critically compare and contrast the performance of the two groups according to perceptual and cognitive tasks. From a Receiver Operating Curve (ROC) analysis, we conclude that the provision of computer-processed images alongside the original ultrasound images, significantly improve the perceptual tasks of non-radiologists but only marginal improvements are shown in the perceptual and cognitive tasks of the group of expert radiologists.

  10. Synergism between dipyridamole and cisplatin in human breast cancer cells in vitro

    Directory of Open Access Journals (Sweden)

    Janice R. Perussi

    2003-05-01

    Full Text Available Cisplatin is very effective in the treatment of metastatic breast cancer. However, the development of cellular resistance is a serious problem in cisplatin chemotherapy. In the present work, the effects of dipyridamole (DPM on the cellular accumulation and cytotoxicity of cisplatin was studied in cisplatinsensitive (MDA/S and cisplatinresistant (MDA/R human breast cancer cells. In the presence of 30 µM DPM, the IC50 of cisplatin was reduced by 39% for both cell lines. Combination index analysis revealed that cisplatin and dipyridamole interact synergistically in MDA/R cells. In the MDA/S cells, the cellular accumulation of cisplatin increased by 57 ± 8% in the presence of 30 µM DPM. In the MDA/R cells, the cellular accumulation of cisplatin remained the same with or without 30 µM DPM. The results suggest that the enhancement of cisplatin cytotoxicity by DPM in MDA/S cells may be related to a DPM-induced increase in cisplatin accumulation, but the enhanced cytotoxicity in MDA/R cells employs a mechanism that does not involve an increase in the cellular accumulation of cisplatin.

  11. Inhibitory effects and molecular mechanisms of tetrahydrocurcumin against human breast cancer MCF-7 cells

    Directory of Open Access Journals (Sweden)

    Xiao Han

    2016-02-01

    Full Text Available Background: Tetrahydrocurcumin (THC, an active metabolite of curcumin, has been reported to have similar biological effects to curcumin, but the mechanism of the antitumor activity of THC is still unclear. Methods: The present study was to investigate the antitumor effects and mechanism of THC in human breast cancer MCF-7 cells using the methods of MTT assay, LDH assay, flow cytometry analysis, and western blot assay. Results: THC was found to have markedly cytotoxic effect and antiproliferative activity against MCF-7 cells in a dose-dependent manner with the IC50 for 24 h of 107.8 μM. Flow cytometry analysis revealed that THC mediated the cell-cycle arrest at G0/G1 phase, and 32.8% of MCF-7 cells entered the early phase of apoptosis at 100 μM for 24 h. THC also dose-dependently led to apoptosis in MCF-7 cells via the mitochondrial pathway, as evidenced by the activation of caspase-3 and caspase-9, the elevation of intracellular ROS, a decrease in Bcl-2 and PARP expression, and an increase in Bax expression. Meanwhile, cytochrome C was released to cytosol and the loss of mitochondria membrane potential (Δψm was observed after THC treatment. Conclusion: THC is an excellent source of chemopreventive agents in the treatment of breast cancer and has excellent potential to be explored as antitumor precursor compound.

  12. Effect of pasteurization on selected immune components of donated human breast milk.

    Science.gov (United States)

    Ewaschuk, J B; Unger, S; O'Connor, D L; Stone, D; Harvey, S; Clandinin, M T; Field, C J

    2011-09-01

    Pasteurized, donated milk is increasingly provided to preterm infants in the absence of mother's own milk. The aim of this study was to determine the effect of pasteurization on the concentration of selected components in donated human breast milk. Donated milk from 34 mothers was pooled into 17 distinct batches (4 mothers per batch). Aliquots of each batch were then Holder pasteurized (62.5 °C for 30 min). Interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70 and IL-13 were measured in a multiplex enzyme-linked immunosorbent assay (ELISA). Granulocyte colony-stimulating factor (G-CSF), heparin-binding epidermal-like growth factor (HB-EGF) and hepatocyte growth factor (HGF) were measured by ELISA. Lipids were assessed by gas chromatography and gangliosides by the resorcinol-HCl reaction. IFN-γ, TNF-α, IL-1β, IL-10 and HGF were significantly reduced by pasteurization (PPasteurization significantly reduced the concentration of several immunoactive compounds present in breast milk, but did not have an impact on others.

  13. Processed images in human perception: A case study in ultrasound breast imaging

    International Nuclear Information System (INIS)

    Yap, Moi Hoon; Edirisinghe, Eran; Bez, Helmut

    2010-01-01

    Two main research efforts in early detection of breast cancer include the development of software tools to assist radiologists in identifying abnormalities and the development of training tools to enhance their skills. Medical image analysis systems, widely known as Computer-Aided Diagnosis (CADx) systems, play an important role in this respect. Often it is important to determine whether there is a benefit in including computer-processed images in the development of such software tools. In this paper, we investigate the effects of computer-processed images in improving human performance in ultrasound breast cancer detection (a perceptual task) and classification (a cognitive task). A survey was conducted on a group of expert radiologists and a group of non-radiologists. In our experiments, random test images from a large database of ultrasound images were presented to subjects. In order to gather appropriate formal feedback, questionnaires were prepared to comment on random selections of original images only, and on image pairs consisting of original images displayed alongside computer-processed images. We critically compare and contrast the performance of the two groups according to perceptual and cognitive tasks. From a Receiver Operating Curve (ROC) analysis, we conclude that the provision of computer-processed images alongside the original ultrasound images, significantly improve the perceptual tasks of non-radiologists but only marginal improvements are shown in the perceptual and cognitive tasks of the group of expert radiologists.

  14. Tubulin binding cofactor C (TBCC) suppresses tumor growth and enhances chemosensitivity in human breast cancer cells

    International Nuclear Information System (INIS)

    Hage-Sleiman, Rouba; Herveau, Stéphanie; Matera, Eva-Laure; Laurier, Jean-Fabien; Dumontet, Charles

    2010-01-01

    Microtubules are considered major therapeutic targets in patients with breast cancer. In spite of their essential role in biological functions including cell motility, cell division and intracellular transport, microtubules have not yet been considered as critical actors influencing tumor cell aggressivity. To evaluate the impact of microtubule mass and dynamics on the phenotype and sensitivity of breast cancer cells, we have targeted tubulin binding cofactor C (TBCC), a crucial protein for the proper folding of α and β tubulins into polymerization-competent tubulin heterodimers. We developed variants of human breast cancer cells with increased content of TBCC. Analysis of proliferation, cell cycle distribution and mitotic durations were assayed to investigate the influence of TBCC on the cell phenotype. In vivo growth of tumors was monitored in mice xenografted with breast cancer cells. The microtubule dynamics and the different fractions of tubulins were studied by time-lapse microscopy and lysate fractionation, respectively. In vitro sensitivity to antimicrotubule agents was studied by flow cytometry. In vivo chemosensitivity was assayed by treatment of mice implanted with tumor cells. TBCC overexpression influenced tubulin fraction distribution, with higher content of nonpolymerizable tubulins and lower content of polymerizable dimers and microtubules. Microtubule dynamicity was reduced in cells overexpressing TBCC. Cell cycle distribution was altered in cells containing larger amounts of TBCC with higher percentage of cells in G2-M phase and lower percentage in S-phase, along with slower passage into mitosis. While increased content of TBCC had little effect on cell proliferation in vitro, we observed a significant delay in tumor growth with respect to controls when TBCC overexpressing cells were implanted as xenografts in vivo. TBCC overexpressing variants displayed enhanced sensitivity to antimicrotubule agents both in vitro and in xenografts. These

  15. Prevalence of human papillomavirus genotypes associated with cervical and breast cancers in iran.

    Science.gov (United States)

    Hossein, Rassi; Behzad, Salehi; Tahar, Mohammadian; Azadeh, Nahavandi Araghi

    2013-12-01

    Cancer is a multi-step disease, and infection with a DNA virus could play a role in one or more of the steps in this pathogenic process. High-risk human papillomaviruses (HPV) are the causative agent of several cancers. In this study, we determined the prevalence and genotype distribution of HPV infection among Iranian patients with cervix lesions (CL) and breast cancer (BC). The study group consisted of postoperative tissues from patients diagnosed with cervix lesions and breast cancer. We analyzed 250 formalin-fixed, paraffin-embedded tissue blocks from 100 cervix lesions and 150 breast cancer samples. Verification of each cancer reported in a relative was sought through the pathology reports of the hospital records. Cervix lesions were collected from 100 patients with squamous metaplasia (SM, n=50), cervical intraepithelial neoplasia (CINI, n=18, CINII or III, n=8), and cervical carcinoma (CC, n=24). In this study we evaluated the prevalence of HPV by multiplex PCR in cervix lesions and breast cancer. For paraffin-embedded tissues, DNA extracted by the simple boiling method yielded higher proportions of successful gene amplification (99%) for b-actin gene. Overall prevalence of HPV infection was 6% in the SM group, 34.61% in the CIN group, 75% in the CC group, and 34.66% in the BC group. Furthermore, MY09/11 consensus PCR failed to detect 44 (55.69%) of all HPV infections and interestingly, the predominant genotype detected in all cancers was the oncogenic variant HPV16/18; about 34% of women aged 24 to 54 were infected with at least one type of HPV. Our results demonstrate that DNA derived from archival tissues that archived for less than 8 years could be used successfully for HPV genotyping by multiplex PCR. Infection with HPV was prevalent among Iranian women with CC and BC. The results indicate a likely causal role for high-risk HPV in CC and BC, and also offer the possibility of primary prevention of these cancers by vaccination against HPV in Iran.

  16. Identification and characterization of locus specific methylation patterns within novel loci undergoing hypermethylation during breast cancer pathogenesis

    DEFF Research Database (Denmark)

    Wojdacz, Tomasz K; Windeløv, Johanne Agerlin; Thestrup, Britta B

    2014-01-01

    (DMRs) was validated using Methylation Sensitive High Resolution Melting (MS-HRM) in a case control study on a panel of breast carcinomas (N = 275) and non-malignant controls (N = 74). RESULTS: Based on microarray results we selected 19 DMRs for large-scale screening of cases and controls. Analysis...

  17. Efficacy and immunogenicity of live-attenuated human rotavirus vaccine in breast-fed and formula-fed European infants.

    Science.gov (United States)

    Vesikari, Timo; Prymula, Roman; Schuster, Volker; Tejedor, Juan-C; Cohen, Robert; Bouckenooghe, Alain; Damaso, Silvia; Han, Htay Htay

    2012-05-01

    Rotavirus is the main cause of severe gastroenteritis and diarrhea in infants and young children less than 5 years of age. Potential impact of breast-feeding on the efficacy and immunogenicity of human rotavirus G1P[8] vaccine was examined in this exploratory analysis. Healthy infants (N = 3994) aged 6-14 weeks who received 2 doses of human rotavirus vaccine/placebo according to a 0-1 or 0-2 month schedule were followed for rotavirus gastroenteritis during 2 epidemic seasons. Rotavirus IgA seroconversion rate (anti-IgA antibody concentration ≥ 20 mIU/mL) and geometric mean concentrations were measured prevaccination and 1-2 months post-dose 2. Vaccine efficacy against any and severe rotavirus gastroenteritis was analyzed according to the infants being breast-fed or exclusively formula-fed at the time of vaccination. Antirotavirus IgA seroconversion rate was 85.5% (95% confidence interval [CI]: 82.4-88.3) in breast-fed and 89.2% (95% CI: 84.2-93) in exclusively formula-fed infants; geometric mean concentrations in the respective groups were 185.8 U/mL (95% CI: 161.4-213.9) and 231.5 U/mL (95% CI: 185.9-288.2). Vaccine efficacy was equally high in breast-fed and exclusively formula-fed children in the first season but fell in breast-fed infants in the second rotavirus season. During the combined 2-year efficacy follow-up period, vaccine efficacy against any rotavirus gastroenteritis was 76.2% (95% CI: 68.7-82.1) and 89.8% (95% CI: 77.6-95.9) and against severe rotavirus gastroenteritis 88.4% (95% CI: 81.6-93) and 98.1% (95% CI: 88.2-100) in the breast-fed and exclusively formula-fed infants, respectively. The difference in immunogenicity of human rotavirus vaccine in breast-fed and exclusively formula-fed infants was small. Vaccine efficacy was equally high in breast-fed and exclusively formula-fed children in the first season. Breast-feeding seemed to reduce slightly the efficacy in the second season.

  18. Organohalogen compounds in human breast milk from Republic of Buryatia, Russia

    Energy Technology Data Exchange (ETDEWEB)

    Tsydenova, Oyuna V. [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Sudaryanto, Agus [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Kajiwara, Natsuko [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Kunisue, Tatsuya [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Batoev, Valeriy B. [Baikal Institute of Nature Management, Siberian Branch of Russian Academy of Sciences, Sakhyanova st. 6, Ulan-Ude 670047 (Russian Federation); Tanabe, Shinsuke [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan)]. E-mail: shinsuke@agr.ehime-u.ac.jp

    2007-03-15

    Human breast milk samples collected during 2003/04 in Buryatia, a Russian autonomous republic, were analyzed in order to assess human exposure to organohalogen compounds including organochlorine pesticides, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs). When compared with available worldwide data, levels of HCB (23-880 ng/g lipid wt.), PCBs (69-680 ng/g lipid wt.), and HCHs (100-3700 ng/g lipid wt.) were relatively high, indicating elevated human exposure to these organochlorines (OCs) in Buryatia. In contrast to OCs, PBDE concentrations were low (0.46-1.7 ng/g lipid wt.). Out of 14 BDE congeners analyzed, BDE-28, BDE-47, BDE-100, BDE-153, BDE-197, and BDE-207 were detected. Estimated daily intakes (EDIs) of HCHs, HCB, CHLs, and PCBs by infants solely from human milk for 100%, 43%, 34%, and 17% of the samples, respectively, exceeded guideline thresholds. Although high EDIs raise concern for possible toxic effects of OCs, women in Buryatia are recommended to breastfeed due to numerous advantages of breastfeeding for mother and child. - People in the Republic of Buryatia, Russia are exposed to relatively high levels of HCHs, HCB and PCBs.

  19. Organohalogen compounds in human breast milk from Republic of Buryatia, Russia

    International Nuclear Information System (INIS)

    Tsydenova, Oyuna V.; Sudaryanto, Agus; Kajiwara, Natsuko; Kunisue, Tatsuya; Batoev, Valeriy B.; Tanabe, Shinsuke

    2007-01-01

    Human breast milk samples collected during 2003/04 in Buryatia, a Russian autonomous republic, were analyzed in order to assess human exposure to organohalogen compounds including organochlorine pesticides, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs). When compared with available worldwide data, levels of HCB (23-880 ng/g lipid wt.), PCBs (69-680 ng/g lipid wt.), and HCHs (100-3700 ng/g lipid wt.) were relatively high, indicating elevated human exposure to these organochlorines (OCs) in Buryatia. In contrast to OCs, PBDE concentrations were low (0.46-1.7 ng/g lipid wt.). Out of 14 BDE congeners analyzed, BDE-28, BDE-47, BDE-100, BDE-153, BDE-197, and BDE-207 were detected. Estimated daily intakes (EDIs) of HCHs, HCB, CHLs, and PCBs by infants solely from human milk for 100%, 43%, 34%, and 17% of the samples, respectively, exceeded guideline thresholds. Although high EDIs raise concern for possible toxic effects of OCs, women in Buryatia are recommended to breastfeed due to numerous advantages of breastfeeding for mother and child. - People in the Republic of Buryatia, Russia are exposed to relatively high levels of HCHs, HCB and PCBs

  20. Functional screen for genes responsible for tamoxifen resistance in human breast cancer cells

    NARCIS (Netherlands)

    Meijer, Danielle; van Agthoven, Ton; Bosma, Peter T.; Nooter, Kees; Dorssers, Lambert C. J.

    2006-01-01

    Antiestrogens, such as tamoxifen, are widely used for endocrine treatment of estrogen receptor-positive breast cancer. However, as breast cancer progresses, development of tamoxifen resistance is inevitable. The mechanisms underlying this resistance are not well understood. To identify genes

  1. MUC-1-ESA+ progenitor cells in normal benign and malignant human breast epithelial cells

    OpenAIRE

    Lu, Xinquan; Li, Huixiang; Xu, Kejia; Nesland, Jahn M.; Suo, Zhenhe

    2009-01-01

    The existence of mammary epithelial stem/progenitor cells has been demonstrated in MUC-1-/ ESA+ subpopulations of breast epithelial cells. However, knowledge about the expression and localization in benign and malignant breast lesions is unknown. Using a double-staining immunohistochemistry method, we investigated MUC-1-/ESA+ cells in 10 normal breast tissues, 49 cases with fibrocystic disease, 40 fibroadenomas, 36 invasive ductal carcinomas and the breast cancer ce...

  2. Anti-cancer effects of bioactive compounds from rose hip fruit in human breast cancer cell lines

    OpenAIRE

    Zhong, Lijie

    2017-01-01

    Rose hips have long been used in human diets as a food ingredient and supplement. Their multiple medical properties, which have been attributed to their abundant carotenoid composition, have attracted widespread scientific attention. This thesis examined the carotenoid composition in rose hips from five rose species. The anti-cancer effect of different carotenoid fractions from rose hips was investigated in human breast cancer cell lines, using the natural variation in carotenoid content in h...

  3. Prevalence and factors associated with breast milk donation in banks that receive human milk in primary health care units,

    OpenAIRE

    Meneses, Tatiana Mota Xavier de; Oliveira, Maria Inês Couto de; Boccolini, Cristiano Siqueira

    2017-01-01

    Abstract Objective: To estimate the prevalence and to analyze factors associated with breast milk donation at primary health care units in order to increase the human milk bank reserves. Methods: Cross-sectional study carried out in 2013 in Rio de Janeiro, Brazil. A representative sample of 695 mothers of children younger than 1 year attended to at the nine primary health care units with human milk donation services were interviewed. A hierarchical approach was used to obtain adjusted preva...

  4. Prevalence and factors associated with breast milk donation in banks that receive human milk in primary health care units

    OpenAIRE

    Tatiana Mota Xavier de Meneses; Maria Inês Couto de Oliveira; Cristiano Siqueira Boccolini

    2017-01-01

    Abstract Objective: To estimate the prevalence and to analyze factors associated with breast milk donation at primary health care units in order to increase the human milk bank reserves. Methods: Cross-sectional study carried out in 2013 in Rio de Janeiro, Brazil. A representative sample of 695 mothers of children younger than 1 year attended to at the nine primary health care units with human milk donation services were interviewed. A hierarchical approach was used to obtain adjusted preva...

  5. Trace elemental analysis of human breast cancerous blood by advanced PC-WDXRF technique

    Science.gov (United States)

    Singh, Ranjit; Kainth, Harpreet Singh; Prasher, Puneet; Singh, Tejbir

    2018-03-01

    The objective of this work is to quantify the trace elements of healthy and non-healthy blood samples by using advanced polychromatic source based wavelength dispersive X-ray fluorescence (PC-WDXRF) technique. The imbalances in trace elements present in the human blood directly or indirectly lead to the carcinogenic process. The trace elements 11Na, 12Mg, 15P, 16S, 17Cl, 19K, 20Ca, 26Fe, 29Cu and 30Zn are identified and their concentrations are estimated. The experimental results clearly discuss the variation and role of various trace elements present in the non-healthy blood samples relative to the healthy blood samples. These results establish future guidelines to probe the possible roles of essential trace elements in the breast carcinogenic processes. The instrumental sensitivity and detection limits for measuring the elements in the atomic range 11 ≤ Z ≤ 30 have also been discussed in the present work.

  6. Characterization of human breast disease using phosphorus magnetic resonance spectroscopy and proton magnetic resonance imaging

    International Nuclear Information System (INIS)

    Merchant, T.E.

    1992-01-01

    This thesis provides the fundamental characterization and differentiation of breast tissues using in vivo and ex vivo MR techniques in the hope that these techniques and experimental findings will be used on a larger scale and in a predictive manner in order to improve the specificity of diagnosis and treatment of breast cancer. In this dissertation, clinical studies were performed using proton magnetic resonance imaging and phosphorus magnetic resonance spectro-scopy ( 31 P MRS) to characterize and differentiate malignant breast tumors, benign breast tumors and normal breast tissues in vivo. These studies were carried out following the methodical characterization of chemical extracts of malignant breast tumor, benign breast tumor and normal breast parenchymal surgical tissue specimens using high resolution 31 P MRS. Alterations in breast tissue metabolism, as a result of pathological processes, were postulated to be responsible for measurable differences between malignant breast tumors, benign breast tumors and normal breast tissues using magnetic resonance techniques. (author). 365 refs.; 37 figs.; 25 tabs

  7. N-3 Polyunsaturated Fatty Acids of Marine Origin and Multifocality in Human Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Lobna Ouldamer

    Full Text Available The microenvironment of breast epithelial tissue may contribute to the clinical expression of breast cancer. Breast epithelial tissue, whether healthy or tumoral, is directly in contact with fat cells, which in turn could influence tumor multifocality. In this pilot study we investigated whether the fatty acid composition of breast adipose tissue differed according to breast cancer focality.Twenty-three consecutive women presenting with non-metastatic breast cancer underwent breast-imaging procedures including Magnetic Resonance Imaging prior to treatment. Breast adipose tissue specimens were collected during breast surgery. We established a biochemical profile of adipose tissue fatty acids by gas chromatography. We assessed whether there were differences according to breast cancer focality.We found that decreased levels in breast adipose tissue of docosahexaenoic and eicosapentaenoic acids, the two main polyunsaturated n-3 fatty acids of marine origin, were associated with multifocality.These differences in lipid content may contribute to mechanisms through which peritumoral adipose tissue fuels breast cancer multifocality.

  8. Generation of a suite of 3D computer-generated breast phantoms from a limited set of human subject data

    International Nuclear Information System (INIS)

    Hsu, Christina M. L.; Palmeri, Mark L.; Segars, W. Paul; Veress, Alexander I.; Dobbins, James T. III

    2013-01-01

    Purpose: The authors previously reported on a three-dimensional computer-generated breast phantom, based on empirical human image data, including a realistic finite-element based compression model that was capable of simulating multimodality imaging data. The computerized breast phantoms are a hybrid of two phantom generation techniques, combining empirical breast CT (bCT) data with flexible computer graphics techniques. However, to date, these phantoms have been based on single human subjects. In this paper, the authors report on a new method to generate multiple phantoms, simulating additional subjects from the limited set of original dedicated breast CT data. The authors developed an image morphing technique to construct new phantoms by gradually transitioning between two human subject datasets, with the potential to generate hundreds of additional pseudoindependent phantoms from the limited bCT cases. The authors conducted a preliminary subjective assessment with a limited number of observers (n= 4) to illustrate how realistic the simulated images generated with the pseudoindependent phantoms appeared. Methods: Several mesh-based geometric transformations were developed to generate distorted breast datasets from the original human subject data. Segmented bCT data from two different human subjects were used as the “base” and “target” for morphing. Several combinations of transformations were applied to morph between the “base’ and “target” datasets such as changing the breast shape, rotating the glandular data, and changing the distribution of the glandular tissue. Following the morphing, regions of skin and fat were assigned to the morphed dataset in order to appropriately assign mechanical properties during the compression simulation. The resulting morphed breast was compressed using a finite element algorithm and simulated mammograms were generated using techniques described previously. Sixty-two simulated mammograms, generated from morphing

  9. Parabens can enable hallmarks and characteristics of cancer in human breast epithelial cells: a review of the literature with reference to new exposure data and regulatory status.

    Science.gov (United States)

    Darbre, Philippa D; Harvey, Philip W

    2014-09-01

    A framework for understanding the complexity of cancer development was established by Hanahan and Weinberg in their definition of the hallmarks of cancer. In this review, we consider the evidence that parabens can enable development in human breast epithelial cells of four of six of the basic hallmarks, one of two of the emerging hallmarks and one of two of the enabling characteristics. In Hallmark 1, parabens have been measured as present in 99% of human breast tissue samples, possess oestrogenic activity and can stimulate sustained proliferation of human breast cancer cells at concentrations measurable in the breast. In Hallmark 2, parabens can inhibit the suppression of breast cancer cell growth by hydroxytamoxifen, and through binding to the oestrogen-related receptor gamma may prevent its deactivation by growth inhibitors. In Hallmark 3, in the 10 nm-1 μm range, parabens give a dose-dependent evasion of apoptosis in high-risk donor breast epithelial cells. In Hallmark 4, long-term exposure (>20 weeks) to parabens leads to increased migratory and invasive activity in human breast cancer cells, properties that are linked to the metastatic process. As an emerging hallmark methylparaben has been shown in human breast epithelial cells to increase mTOR, a key regulator of energy metabolism. As an enabling characteristic parabens can cause DNA damage at high concentrations in the short term but more work is needed to investigate long-term, low-dose mixtures. The ability of parabens to enable multiple cancer hallmarks in human breast epithelial cells provides grounds for regulatory review of the implications of the presence of parabens in human breast tissue. Copyright © 2014 John Wiley & Sons, Ltd.

  10. 'A novel in vivo model for the study of human breast cancer metastasis using primary breast tumor-initiating cells from patient biopsies'

    International Nuclear Information System (INIS)

    Marsden, Carolyn G; Wright, Mary Jo; Carrier, Latonya; Moroz, Krzysztof; Pochampally, Radhika; Rowan, Brian G

    2012-01-01

    The study of breast cancer metastasis depends on the use of established breast cancer cell lines that do not accurately represent the heterogeneity and complexity of human breast tumors. A tumor model was developed using primary breast tumor-initiating cells isolated from patient core biopsies that would more accurately reflect human breast cancer metastasis. Tumorspheres were isolated under serum-free culture conditions from core biopsies collected from five patients with clinical diagnosis of invasive ductal carcinoma (IDC). Isolated tumorspheres were transplanted into the mammary fat pad of NUDE mice to establish tumorigenicity in vivo. Tumors and metastatic lesions were analyzed by hematoxylin and eosin (H+E) staining and immunohistochemistry (IHC). Tumorspheres were successfully isolated from all patient core biopsies, independent of the estrogen receptor α (ERα)/progesterone receptor (PR)/Her2/neu status or tumor grade. Each tumorsphere was estimated to contain 50-100 cells. Transplantation of 50 tumorspheres (1-5 × 10 3 cells) in combination with Matrigel into the mammary fat pad of NUDE mice resulted in small, palpable tumors that were sustained up to 12 months post-injection. Tumors were serially transplanted three times by re-isolation of tumorspheres from the tumors and injection into the mammary fat pad of NUDE mice. At 3 months post-injection, micrometastases to the lung, liver, kidneys, brain and femur were detected by measuring content of human chromosome 17. Visible macrometastases were detected in the lung, liver and kidneys by 6 months post-injection. Primary tumors variably expressed cytokeratins, Her2/neu, cytoplasmic E-cadherin, nuclear β catenin and fibronectin but were negative for ERα and vimentin. In lung and liver metastases, variable redistribution of E-cadherin and β catenin to the membrane of tumor cells was observed. ERα was re-expressed in lung metastatic cells in two of five samples. Tumorspheres isolated under defined culture

  11. New reconstruction algorithm for digital breast tomosynthesis: better image quality for humans and computers.

    Science.gov (United States)

    Rodriguez-Ruiz, Alejandro; Teuwen, Jonas; Vreemann, Suzan; Bouwman, Ramona W; van Engen, Ruben E; Karssemeijer, Nico; Mann, Ritse M; Gubern-Merida, Albert; Sechopoulos, Ioannis

    2017-01-01

    Background The image quality of digital breast tomosynthesis (DBT) volumes depends greatly on the reconstruction algorithm. Purpose To compare two DBT reconstruction algorithms used by the Siemens Mammomat Inspiration system, filtered back projection (FBP), and FBP with iterative optimizations (EMPIRE), using qualitative analysis by human readers and detection performance of machine learning algorithms. Material and Methods Visual grading analysis was performed by four readers specialized in breast imaging who scored 100 cases reconstructed with both algorithms (70 lesions). Scoring (5-point scale: 1 = poor to 5 = excellent quality) was performed on presence of noise and artifacts, visualization of skin-line and Cooper's ligaments, contrast, and image quality, and, when present, lesion visibility. In parallel, a three-dimensional deep-learning convolutional neural network (3D-CNN) was trained (n = 259 patients, 51 positives with BI-RADS 3, 4, or 5 calcifications) and tested (n = 46 patients, nine positives), separately with FBP and EMPIRE volumes, to discriminate between samples with and without calcifications. The partial area under the receiver operating characteristic curve (pAUC) of each 3D-CNN was used for comparison. Results EMPIRE reconstructions showed better contrast (3.23 vs. 3.10, P = 0.010), image quality (3.22 vs. 3.03, P algorithm provides DBT volumes with better contrast and image quality, fewer artifacts, and improved visibility of calcifications for human observers, as well as improved detection performance with deep-learning algorithms.

  12. Apoptotic Cell Death and the Proliferative Capacity of Human Breast Cancers

    Directory of Open Access Journals (Sweden)

    Gabriele A. Losa

    1998-01-01

    Full Text Available The proliferative capacity (%S‐phase fraction, DNA ploidy, apoptosis frequency (DNA fragmentation and steroid hormone receptor status (estrogen receptor, ER; progesterone receptor, PR of 110 samples of human breast tissues with ductal invasive carcinoma were measured using biochemical and cytofluorimetric procedures. The DNA fragmentation had a left‐skewed frequency distribution and an overall median value of 1.64%, whilst the median %S‐phase fraction was 8%. The median %DNA fragmentation and %S‐phase fraction were 1.96% and 16% in hyperdiploid tumours (n=29; DNA index >1.1 higher than in hypodiploid tumors (n=10; DNA index 0.96, 0.38% and 7.5%. DNA diploid tumours (n=71 had median %DNA fragmentation and %S‐phase values of 1.68% and 6%, consistently lower than the median values of DNA hyperdiploid tumours. The ER content of hypodiploid tumours was about one half (median: 5.9 fmol/mg the median values in hyperdiploid (10.6 fmol/mg and diploid tumours (14.6 fmol/mg. This may correlate with the lowest frequency of apoptosis in hypodiploid tumours, at least when measured by biochemical methods which only detect cells in the late phases of apoptosis. In contrast, the median PR was lowest in hyperdiploid tumours than in hypo and/or diploid tumours. The %S‐phase/%fragmented DNA ratio for the hypodiploid tumours was 19.7, significantly higher than the ratios for hyperdiploid (8.2 and diploid tumours (3.6. These findings indicated that there is an imbalance between proliferative capacity and cell death or growth arrest in human breast tumours. This imbalance may well be linked to a loss of steroid hormone control.

  13. Benzyl isothiocyanate causes FoxO1-mediated autophagic death in human breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Dong Xiao

    Full Text Available Benzyl isothiocyanate (BITC, a constituent of edible cruciferous vegetables, inhibits growth of breast cancer cells but the mechanisms underlying growth inhibitory effect of BITC are not fully understood. Here, we demonstrate that BITC treatment causes FoxO1-mediated autophagic death in cultured human breast cancer cells. The BITC-treated breast cancer cells (MDA-MB-231, MCF-7, MDA-MB-468, BT-474, and BRI-JM04 and MDA-MB-231 xenografts from BITC-treated mice exhibited several features characteristic of autophagy, including appearance of double-membrane vacuoles (transmission electron microscopy and acidic vesicular organelles (acridine orange staining, cleavage of microtubule-associated protein 1 light chain 3 (LC3, and/or suppression of p62 (p62/SQSTM1 or sequestosome 1 expression. On the other hand, a normal human mammary epithelial cell line (MCF-10A was resistant to BITC-induced autophagy. BITC-mediated inhibition of MDA-MB-231 and MCF-7 cell viability was partially but statistically significantly attenuated in the presence of autophagy inhibitors 3-methyl adenine and bafilomycin A1. Stable overexpression of Mn-superoxide dismutase, which was fully protective against apoptosis, conferred only partial protection against BITC-induced autophagy. BITC treatment decreased phosphorylation of mTOR and its downstream targets (P70s6k and 4E-BP1 in cultured MDA-MB-231 and MCF-7 cells and MDA-MB-231 xenografts, but activation of mTOR by transient overexpression of its positive regulator Rheb failed to confer protection against BITC-induced autophagy. Autophagy induction by BITC was associated with increased expression and acetylation of FoxO1. Furthermore, autophagy induction and cell growth inhibition resulting from BITC exposure were significantly attenuated by small interfering RNA knockdown of FoxO1. In conclusion, the present study provides novel insights into the molecular circuitry of BITC-induced cell death involving FoxO1-mediated autophagy.

  14. Human breast tumor imaging using 111In labeled monoclonal antibody: Anthymic mouse model

    International Nuclear Information System (INIS)

    Ban An Khaw; Massachusetts General Hospital, Boston; Bailes, J.S.; Schneider, S.L.; Lancaster, J.; Lasher, J.C.; McGuire, W.L.; Powers, J.; Strauss, H.W.

    1988-01-01

    The monoclonal antibody (MoAb) 323/A3, an IgG1, was raised against the human breast tumor cell line MCF-7 and recognized a 43 Kd membrane associated glycoprotein. Histochemical studies with the antibody detected 75% of metastatic lymph nodes, 59% of primary breast tumors, and showed some staining in 20% of benign breast lesions. For radionuclide imaging, the MoAb 323/A3 was labeled with both 125 I and 111 In, via covalently coupled diethylenetriaminepentaacetic acid (DTPA) by the mixed anhydride method. The antibody activity of the DTPA modified 323/A3 was assessed by an immunoassay using viable and fixed MCF-7 target cells. Male athymic nude mice bearing BT-20 human mammary tumors were injected with dual 125 I/ 111 In labeled DTPA 323/A3 via the tail veins. The animals were imaged with a gamma camera equipped with a pinhole collimator at 1-3 h, 1, 2, 3, 4 and 5 days after the tracer administration. On day 5 or 6, the animals were killed, and the biodistribution of the radiotracers was determined for the blood, thyroid, heart, lungs, liver, spleen, kidneys, gastro-intestinal tract and tumor. Target to blood ratio at 6 days for the 111 In tracer was 24:1 in the group with a mean tumor weight of 0.492 g, and 13:1 in another group with a mean tumor weight of 0.1906 g (day 5). However, the 125 I activity showed only 3.6:1 and 5.4:1 target to blood ratios in the corresponding groups. The larger tumors localized less 111 I tracer (27.13%±7.57% injected dose/g, Mean±SD) than the smaller tumors (52.75%±22.25% ID/g). Analysis of the gamma images showed that the maximum tracer concentration occurred in the tumors at about 2 to 3 days after intravenous tracer administration. The excellent tumor resolution observed with BT-20 tumors may be due to increased 43 Kd glycoprotein antigen density in this tumor cell line. (orig.)

  15. Binding of (/sup 3/H) progesterone to normal and neoplastic tissue samples from tumour bearing breasts

    Energy Technology Data Exchange (ETDEWEB)

    Pollow, K; Sinnecker, R; Schmidt-Gollwitzer, M; Boquoi, E; Pollow, B [Institut fuer Molekularbiologie und Biochemie, Frauenklinik Charlottenburg der Freien Universitat, Berlin (G.F.R.)

    1977-01-01

    Macromolecular components of normal human mammary cytosol (obtained from 'non-malignant tissue samples' from cancer bearing breasts) which bind (/sup 3/H)progesterone in vitro were characterized by sucrose gradient centrifugation, gel filtration on Agarose, ion exchange chromatography, isoelectric focusing, competition studies and kinetic parameters. The size of the cytoplasmic binding components vary with the concentration of KCl. In the absence of KCl, the major components are characterized by sedimentation coefficients of about 4 S and 8 S. In solutions containing 0.3M KCl, the cytoplasmic components sediment at 4 S in sucrose gradient. The corticosteroid-binding component of normal human mammary cytosol both sediment at about the same rate in the presence of 0.3M KCl and chromatograph as a single component on Agarose. The isoelectric point of the progesterone-binding component of normal human mammary cytosol was located around pH 5.0. The progesterone-binding component was more thermo-labile than serum CBG. CBG was inactivated at temperatures above 45 deg C but temperature above 20 deg C destroyed specific progesterone receptor binding. Progesterone receptor concentrations in normal mammary cytosol of premenopausal women depended on the menstrual cycle. The binding of progesterone was highest around the time of ovulation. In breast tumor tissue samples the progesterone receptor concentration was lower than in the normal mammary cytosol (obtained in each case from the same tumor-bearing breast). In 5 out of 37 breast tumor samples progesterone binding activity could not be detected.

  16. Lifespan Extension and Sustained Expression of Stem Cell Phenotype of Human Breast Epithelial Stem Cells in a Medium with Antioxidants

    Directory of Open Access Journals (Sweden)

    Kai-Hung Wang

    2016-01-01

    Full Text Available We have previously reported the isolation and culture of a human breast epithelial cell type with stem cell characteristics (Type I HBEC from reduction mammoplasty using the MSU-1 medium. Subsequently, we have developed several different normal human adult stem cell types from different tissues using the K-NAC medium. In this study, we determined whether this low calcium K-NAC medium with antioxidants (N-acetyl-L-cysteine and L-ascorbic acid-2-phosphate is a better medium to grow human breast epithelial cells. The results clearly show that the K-NAC medium is a superior medium for prolonged growth (cumulative population doubling levels ranged from 30 to 40 of normal breast epithelial cells that expressed stem cell phenotypes. The characteristics of these mammary stem cells include deficiency in gap junctional intercellular communication, expression of Oct-4, and the ability to differentiate into basal epithelial cells and to form organoid showing mammary ductal and terminal end bud-like structures. Thus, this new method of growing Type I HBECs will be very useful in future studies of mammary development, breast carcinogenesis, chemoprevention, and cancer therapy.

  17. Intravital multiphoton imaging reveals multicellular streaming as a crucial component of in vivo cell migration in human breast tumors

    Science.gov (United States)

    Patsialou, Antonia; Bravo-Cordero, Jose Javier; Wang, Yarong; Entenberg, David; Liu, Huiping; Clarke, Michael; Condeelis, John S.

    2014-01-01

    Metastasis is the main cause of death in breast cancer patients. Cell migration is an essential component of almost every step of the metastatic cascade, especially the early step of invasion inside the primary tumor. In this report, we have used intravital multiphoton microscopy to visualize the different migration patterns of human breast tumor cells in live primary tumors. We used xenograft tumors of MDA-MB-231 cells as well as a low passage xenograft tumor from orthotopically injected patient-derived breast tumor cells. Direct visualization of human tumor cells in vivo shows two patterns of high-speed migration inside primary tumors: a. single cells and b. multicellular streams (i.e., cells following each other in a single file but without cohesive cell junctions). Critically, we found that only streaming and not random migration of single cells was significantly correlated with proximity to vessels, with intravasation and with numbers of elevated circulating tumor cells in the bloodstream. Finally, although the two human tumors were derived from diverse genetic backgrounds, we found that their migratory tumor cells exhibited coordinated gene expression changes that led to the same end-phenotype of enhanced migration involving activating actin polymerization and myosin contraction. Our data are the first direct visualization and assessment of in vivo migration within a live patient-derived breast xenograft tumor. PMID:25013744

  18. Identification of the Interaction between P-Glycoprotein and Anxa2 in Multidrug-resistant Human Breast Cancer Cells

    International Nuclear Information System (INIS)

    Zhang, Hai-chang; Zhang, Fei; Wu, Bing; Han, Jing-hua; Ji, Wei; Zhou, Yan; Niu, Rui-fang

    2012-01-01

    To explore the interaction of Anxa2 with P-Glycoprotein (P-gp) in the migration and invasion of the multidrug-resistant (MDR) human breast cancer cell line MCF-7/ADR. A pair of short hairpin RNA (shRNA) targeting P-gp was transfected into MCF-7/ADR cells, and monoclonal cell strains were screened. The expression of P-gp was detected by Western blot. Transwell chambers were used to observe the cell migration capacity and invasion ability. The interaction between P-gp and Anxa2 was examined by immunoprecipitation and immunofluorescence confocal microscopy analyses. P-gp expression was significantly knocked down, and there were notable decreasing trends in the migration and invasion capability of MDR breast cancer cells (P<0.05). There was a close interaction between Anxa2 and P-gp. MCF-7/ADR is an MDR human breast cancer cell line with high migration and invasion abilities. The knockdown of P-gp notably impaired the migration and invasion abilities of the tumor cells. The interaction of Anxa2 with P-pg may play an important role in the enhanced invasiveness of MDR human breast cancer cells

  19. Effects of vitamin D-binding protein-derived macrophage-activating factor on human breast cancer cells.

    Science.gov (United States)

    Pacini, Stefania; Punzi, Tiziana; Morucci, Gabriele; Gulisano, Massimo; Ruggiero, Marco

    2012-01-01

    Searching for additional therapeutic tools to fight breast cancer, we investigated the effects of vitamin D-binding protein-derived macrophage activating factor (DBP-MAF, also known as GcMAF) on a human breast cancer cell line (MCF-7). The effects of DBP-MAF on proliferation, morphology, vimentin expression and angiogenesis were studied by cell proliferation assay, phase-contrast microscopy, immunohistochemistry and western blotting, and chorioallantoic membrane (CAM) assay. DBP-MAF inhibited human breast cancer cell proliferation and cancer cell-stimulated angiogenesis. MCF-7 cells treated with DBP-MAF predominantly grew in monolayer and appeared to be well adherent to each other and to the well surface. Exposure to DBP-MAF significantly reduced vimentin expression, indicating a reversal of the epithelial/mesenchymal transition, a hallmark of human breast cancer progression. These results are consistent with the hypothesis that the known anticancer efficacy of DBP-MAF can be ascribed to different biological properties of the molecule that include inhibition of tumour-induced angiogenesis and direct inhibition of cancer cell proliferation, migration and metastatic potential.

  20. Overexpression of β1-chain-containing laminins in capillary basement membranes of human breast cancer and its metastases

    International Nuclear Information System (INIS)

    Fujita, Manabu; Khazenzon, Natalya M; Bose, Shikha; Sekiguchi, Kiyotoshi; Sasaki, Takako; Carter, William G; Ljubimov, Alexander V; Black, Keith L; Ljubimova, Julia Y

    2005-01-01

    Laminins are the major components of vascular and parenchymal basement membranes. We previously documented a switch in the expression of vascular laminins containing the α4 chain from predominantly laminin-9 (α4β2γ1) to predominantly laminin-8 (α4β1γ1) during progression of human brain gliomas to high-grade glioblastoma multiforme. Here, differential expression of laminins was studied in blood vessels and ductal epithelium of the breast. In the present study the expressions of laminin isoforms α1–α5, β1–β3, γ1, and γ2 were examined during progression of breast cancer. Forty-five clinical samples of breast tissues including normal breast, ductal carcinomas in situ, invasive ductal carcinomas, and their metastases to the brain were compared using Western blot analysis and immunohistochemistry for various chains of laminin, in particular laminin-8 and laminin-9. Laminin α4 chain was observed in vascular basement membranes of most studied tissues, with the highest expression in metastases. At the same time, the expression of laminin β2 chain (a constituent of laminin-9) was mostly seen in normal breast and carcinomas in situ but not in invasive carcinomas or metastases. In contrast, laminin β1 chain (a constituent of laminin-8) was typically found in vessel walls of carcinomas and their metastases but not in those of normal breast. The expression of laminin-8 increased in a progression-dependent manner. A similar change was observed from laminin-11 (α5β2γ1) to laminin-10 (α5β1γ1) during breast tumor progression. Additionally, laminin-2 (α2β1γ1) appeared in vascular basement membranes of invasive carcinomas and metastases. Chains of laminin-5 (α3β3γ2) were expressed in the ductal epithelium basement membranes of the breast and diminished with tumor progression. These results suggest that laminin-2, laminin-8, and laminin-10 are important components of tumor microvessels and may associate with breast tumor progression. Angiogenic switch

  1. Overexpression of β1-chain-containing laminins in capillary basement membranes of human breast cancer and its metastases

    Science.gov (United States)

    Fujita, Manabu; Khazenzon, Natalya M; Bose, Shikha; Sekiguchi, Kiyotoshi; Sasaki, Takako; Carter, William G; Ljubimov, Alexander V; Black, Keith L; Ljubimova, Julia Y

    2005-01-01

    Introduction Laminins are the major components of vascular and parenchymal basement membranes. We previously documented a switch in the expression of vascular laminins containing the α4 chain from predominantly laminin-9 (α4β2γ1) to predominantly laminin-8 (α4β1γ1) during progression of human brain gliomas to high-grade glioblastoma multiforme. Here, differential expression of laminins was studied in blood vessels and ductal epithelium of the breast. Method In the present study the expressions of laminin isoforms α1–α5, β1–β3, γ1, and γ2 were examined during progression of breast cancer. Forty-five clinical samples of breast tissues including normal breast, ductal carcinomas in situ, invasive ductal carcinomas, and their metastases to the brain were compared using Western blot analysis and immunohistochemistry for various chains of laminin, in particular laminin-8 and laminin-9. Results Laminin α4 chain was observed in vascular basement membranes of most studied tissues, with the highest expression in metastases. At the same time, the expression of laminin β2 chain (a constituent of laminin-9) was mostly seen in normal breast and carcinomas in situ but not in invasive carcinomas or metastases. In contrast, laminin β1 chain (a constituent of laminin-8) was typically found in vessel walls of carcinomas and their metastases but not in those of normal breast. The expression of laminin-8 increased in a progression-dependent manner. A similar change was observed from laminin-11 (α5β2γ1) to laminin-10 (α5β1γ1) during breast tumor progression. Additionally, laminin-2 (α2β1γ1) appeared in vascular basement membranes of invasive carcinomas and metastases. Chains of laminin-5 (α3β3γ2) were expressed in the ductal epithelium basement membranes of the breast and diminished with tumor progression. Conclusion These results suggest that laminin-2, laminin-8, and laminin-10 are important components of tumor microvessels and may associate with breast

  2. Subclinical mastitis (SCM) and proinflammatory cytokines are associated with mineral and trace element concentrations in human breast milk.

    Science.gov (United States)

    Li, Chen; Solomons, Noel W; Scott, Marilyn E; Koski, Kristine G

    2018-03-01

    The possibility that either subclinical mastitis (SCM), an inflammatory condition of the breast, or elevations in breast milk proinflammatory cytokines alter breast milk mineral and trace element composition in humans has not been investigated. In this cross-sectional study, breast milk samples (n=108) were collected from Guatemalan Mam-Mayan mothers at one of three stages of lactation (transitional, early and established), and categorized as SCM (Na:K >0.6) or non-SCM (Na:K ≤0.6). Milk concentrations of 12 minerals (calcium, copper, iron, magnesium, manganese, phosphorus, potassium, rubidium, selenium, sodium, strontium, and zinc) and 4 proinflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) were measured by inductively coupled plasma mass spectrometry (ICP-MS), Lachat analyzer or Luminex multiplex bead cytokine assay. SCM was more prevalent during transitional (30%) than early (15.6%) and established (8.9%) lactation. Analysis of variance revealed that breast milk minerals differed by stage of lactation and SCM status. Breast milk minerals with the exception of magnesium were lower in established lactation, whereas SCM was associated with higher selenium and lower phosphorus. Regression models that controlled for lactation stage also confirmed that SCM was associated with lower milk phosphorus and higher milk selenium concentrations. Furthermore, cytokine concentrations were independently associated with several mineral concentrations: IL-1β with higher phosphorus and iron, IL-6 with higher calcium, magnesium, copper and manganese, IL-8 with higher calcium and zinc, and TNF-α with lower iron and manganese. We conclude that milk mineral and trace element concentrations are affected not only by the presence of SCM but also by proinflammatory cytokines in breast milk. Copyright © 2017 Elsevier GmbH. All rights reserved.

  3. Granulocyte-Colony Stimulating Factor Receptor, Tissue Factor, and VEGF-R Bound VEGF in Human Breast Cancer In Loco.

    Science.gov (United States)

    Wojtukiewicz, Marek Z; Sierko, Ewa; Skalij, Piotr; Kamińska, Magda; Zimnoch, Lech; Brekken, Ralf A; Thorpe, Philip E

    2016-01-01

    Doxorubicin and docetaxel-based chemotherapy regimens used in breast cancer patients are associated with high risk of febrile neutropenia (FN). Granulocyte colony-stimulating factors (G-CSF) are recommended for both treating and preventing chemotherapy-induced neutropenia. Increased thrombosis incidence in G-CSF treated patients was reported; however, the underlying mechanisms remain unclear. The principal activator of blood coagulation in cancer is tissue factor (TF). It additionally contributes to cancer progression and stimulates angiogenesis. The main proangiogenic factor is vascular endothelial growth factor (VEGF). The aim of the study was to evaluate granulocyte-colony stimulating factor receptor (G-CSFR), tissue factor (TF) expression and vascular endothelial growth factor receptor (VEGF-R) bound VEGF in human breast cancer in loco. G-CSFR, TF and VEGFR bound VEGF (VEGF: VEGFR) were assessed in 28 breast cancer tissue samples. Immunohistochemical (IHC) methodologies according to ABC technique and double staining IHC procedure were employed utilizing antibodies against G-CSFR, TF and VEGF associated with VEGFR (VEGF: VEGFR). Expression of G-CSFR was demonstrated in 20 breast cancer tissue specimens (71%). In 6 cases (21%) the expression was strong (IRS 9-12). Strong expression of TF was observed in all investigated cases (100%). Moreover, expression of VEGF: VEGFR was visualized in cancer cells (IRS 5-8). No presence of G-CSFR, TF or VEGF: VEGFR was detected on healthy breast cells. Double staining IHC studies revealed co-localization of G-CSFR and TF, G-CSFR and VEGF: VEGFR, as well as TF and VEGF: VEGFR on breast cancer cells and ECs. The results of the study indicate that GCSFR, TF and VEGF: VEGFR expression as well as their co-expression might influence breast cancer biology, and may increase thromboembolic adverse events incidence.

  4. Cancer-selective death of human breast cancer cells by leelamine is mediated by bax and bak activation.

    Science.gov (United States)

    Sehrawat, Anuradha; Kim, Su-Hyeong; Hahm, Eun-Ryeong; Arlotti, Julie A; Eiseman, Julie; Shiva, Sruti S; Rigatti, Lora H; Singh, Shivendra V

    2017-02-01

    The present study is the first to report inhibition of breast cancer cell growth in vitro and in vivo and suppression of self-renewal of breast cancer stem cells (bCSC) by a pine bark component (leelamine). Except for a few recent publications in melanoma, anticancer pharmacology of this interesting phytochemical is largely elusive. Leelamine (LLM) dose-dependently inhibited viability of MDA-MB-231 (triple-negative), MCF-7 (estrogen receptor-positive), and SUM159 (triple-negative) human breast cancer cells in association with apoptotic cell death induction. To the contrary, a normal mammary epithelial cell line derived from fibrocystic breast disease and spontaneously immortalized (MCF-10A) was fully resistant to LLM-mediated cell growth inhibition and apoptosis induction. LLM also inhibited self-renewal of breast cancer stem cells. Apoptosis induction by LLM in breast cancer cells was accompanied by a modest increase in reactive oxygen species production, which was not due to inhibition of mitochondrial electron transport chain complexes. Nevertheless, ectopic expression of manganese superoxide dismutase conferred partial protection against LLM-induced cell death but only at a lower yet pharmacologically relevant concentration. Exposure of breast cancer cells to LLM resulted in (a) induction and/or activation of multidomain proapoptotic proteins Bax and Bak, (b) caspase-9 activation, and (c) cytosolic release of cytochrome c. Bax and Bak deficiency in immortalized fibroblasts conferred significant protection against cell death by LLM. Intraperitoneal administration of LLM (7.5 mg/kg; 5 times/wk) suppressed the growth of orthotopic SUM159 xenografts in mice without any toxicity. In conclusion, the present study provides critical preclinical data to warrant further investigation of LLM. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Leptin upregulates telomerase activity and transcription of human telomerase reverse transcriptase in MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Ren, He, E-mail: herenrh@yahoo.com.cn [Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin Medical University Cancer Hospital, Tianjin (China); Zhao, Tiansuo; Wang, Xiuchao; Gao, Chuntao; Wang, Jian; Yu, Ming [Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin Medical University Cancer Hospital, Tianjin (China); Hao, Jihui, E-mail: jihuihao@yahoo.com [Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin Medical University Cancer Hospital, Tianjin (China)

    2010-03-26

    The aim was to analyze the mechanism of leptin-induced activity of telomerase in MCF-7 breast cancer cells. We found that leptin activated telomerase in a dose-dependent manner; leptin upregulated the expression of Human Telomerase Reverse Transcriptase (hTERT) at mRNA and protein levels; blockade of signal transducer and activator of transcription 3 (STAT3) phosphorylation significantly counteracted leptin-induced hTERT transcription and protein expression; chromatin immunoprecipitation analysis showed that leptin enhanced the binding of STAT3 to the hTERT promoter. This study uncovers a new mechanism of the proliferative effect of leptin on breast cancer cells and provides a new explanation of obesity-related breast cancer.

  6. miR-151-3p Targets TWIST1 to Repress Migration of Human Breast Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Ting-Chih Yeh

    Full Text Available TWIST1 is a highly conserved basic helix-loop-helix transcription factor that contributes to cancer metastasis by promoting an epithelial-mesenchymal transition and repressing E-cadherin gene expression in breast cancer. In this study, we explored the potential role of miR-151 in TWIST1 expression and cancer properties in human breast cancer cells. We found that the human TWIST1 3'UTR contains a potential binging site for miR-151-3p at the putative target sequence 5'-CAGUCUAG-3'. Using a TWIST1-3'UTR luciferase reporter assay, we demonstrated that the target sequence within the TWIST1 3'UTR is required for miR-151-3p regulation of TWIST1 expression. Moreover, we found that ectopic expression of miR-151-3p by infection with adenoviruses expressing miR-151 significantly decreased TWIST1 expression, migration and invasion, but did not affect cell growth and tumorsphere formation of human breast cancer cells. In addition, overexpression of the protein coding region without the 3'UTR of TWIST1 reversed the repression of cell migration by miR-151-3p. Furthermore, knockdown of miR-151-3p increased TWIST1 expression, reduced E-cadherin expression, and enhanced cell migration. In conclusion, these results suggest that miR-151-3p directly regulates TWIST1 expression by targeting the TWIST1 3'UTR and thus repressing the migration and invasion of human breast cancer cells by enhancing E-cadherin expression. Our findings add to accumulating evidence that microRNAs are involved in breast cancer progression by modulating TWIST1 expression.

  7. Synthesis, characterization and in vitro evaluation of exquisite targeting SPIONs–PEG–HER in HER2+ human breast cancer cells

    International Nuclear Information System (INIS)

    Almaki, Javad Hamzehalipour; Nasiri, Rozita; Idris, Ani; Majid, Fadzilah Adibah Abdul; Wong, Tet Soon; Salouti, Mojtaba; Dabagh, Shadab; Marvibaigi, Mohsen; Amini, Neda

    2016-01-01

    A stable, biocompatible and exquisite SPIONs–PEG–HER targeting complex was developed. Initially synthesized superparamagnetic iron oxide nanoparticles (SPIONs) were silanized using 3-aminopropyltrimethoxysilane (APS) as the coupling agent in order to allow the covalent bonding of polyethylene glycol (PEG) to the SPIONs to improve the biocompatibility of the SPIONs. SPIONs–PEG were then conjugated with herceptin (HER) to permit the SPIONs–PEG–HER to target the specific receptors expressed over the surface of the HER2+ metastatic breast cancer cells. Each preparation step was physico-chemically analyzed and characterized by a number of analytical methods including AAS, FTIR spectroscopy, XRD, FESEM, TEM, DLS and VSM. The biocompatibility of SPIONs–PEG–HER was evaluated in vitro on HSF-1184 (human skin fibroblast cells), SK-BR-3 (human breast cancer cells, HER+), MDA-MB-231 (human breast cancer cells, HER−) and MDA-MB-468 (human breast cancer cells, HER−) cell lines by performing MTT and trypan blue assays. The hemolysis analysis results of the SPIONs–PEG–HER and SPIONs–PEG did not indicate any sign of lysis while in contact with erythrocytes. Additionally, there were no morphological changes seen in RBCs after incubation with SPIONs–PEG–HER and SPIONs–PEG under a light microscope. The qualitative and quantitative in vitro targeting studies confirmed the high level of SPION–PEG–HER binding to SK-BR-3 (HER2+ metastatic breast cancer cells). Thus, the results reflected that the SPIONs–PEG–HER can be chosen as a favorable biomaterial for biomedical applications, chiefly magnetic hyperthermia, in the future. (paper)

  8. Identification of H-Ras-Specific Motif for the Activation of Invasive Signaling Program in Human Breast Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Hae-Young Yong

    2011-02-01

    Full Text Available Increased expression and/or activation of H-Ras are often associated with tumor aggressiveness in breast cancer. Previously, we showed that H-Ras, but not N-Ras, induces MCF10A human breast epithelial cell invasion and migration, whereas both H-Ras and N-Ras induce cell proliferation and phenotypic transformation. In an attempt to determine the sequence requirement directing the divergent phenotype induced by H-Ras and N-Ras with a focus on the induction of human breast cell invasion, we investigated the structural and functional relationships between H-Ras and N-Ras using domain-swap and site-directed mutagenesis approaches. Here, we report that the hypervariable region (HVR, consisting of amino acids 166 to 189 in H-Ras, determines the invasive/migratory signaling program as shown by the exchange of invasive phenotype by swapping HVR sequences between H-Ras and N-Ras. We also demonstrate that the H-Ras-specific additional palmitoylation site at Cys184 is not responsible for the signaling events that distinguish between H-Ras and N-Ras. Importantly, this work identifies the C-terminal HVR, especially the flexible linker domain with two consecutive proline residues Pro173 and Pro174, as a critical domain that contributes to activation of H-Ras and its invasive potential in human breast epithelial cells. The present study sheds light on the structural basis for the Ras isoform-specific invasive program of breast epithelial cells, providing information for the development of agents that specifically target invasion-related H-Ras pathways in human cancer.

  9. Native human autoantibodies targeting GIPC1 identify differential expression in malignant tumors of the breast and ovary

    International Nuclear Information System (INIS)

    Yavelsky, Victoria; Chan, Gerald; Kalantarov, Gavreel; Trakht, Ilya; Lobel, Leslie; Rohkin, Sarit; Shaco-Levy, Ruthy; Tzikinovsky, Alina; Amir, Tamar; Kohn, Hila; Delgado, Berta; Rabinovich, Alex; Piura, Benjamin

    2008-01-01

    We have been studying the native humoral immune response to cancer and have isolated a library of fully human autoantibodies to a variety of malignancies. We previously described the isolation and characterization of two fully human monoclonal antibodies, 27.F7 and 27.B1, from breast cancer patients that target the protein known as GIPC1, an accessory PDZ-domain binding protein involved in regulation of G-protein signaling. Human monoclonal antibodies, 27.F7 and 27.B1, to GIPC1 demonstrate specific binding to malignant breast cancer tissue with no reactivity with normal breast tissue. The current study employs cELISA, flow cytometry, Western blot analysis as well as immunocytochemistry, and immunohistochemistry. Data is analyzed statistically with the Fisher one-tail and two-tail tests for two independent samples. By screening several other cancer cell lines with 27.F7 and 27.B1 we found consistently strong staining of other human cancer cell lines including SKOV-3 (an ovarian cancer cell line). To further clarify the association of GIPC1 with breast and ovarian cancer we carefully studied 27.F7 and 27.B1 using immunocytochemical and immunohistochemical techniques. An immunohistochemical study of normal ovarian tissue, benign, borderline and malignant ovarian serous tumors, and different types of breast cancer revealed high expression of GIPC1 protein in neoplastic cells. Interestingly, antibodies 27.F7 and 27.B1 demonstrate differential staining of borderline ovarian tumors. Examination of different types of breast cancer demonstrates that the level of GIPC1 expression depends on tumor invasiveness and displays a higher expression than in benign tumors. The present pilot study demonstrates that the GIPC1 protein is overexpressed in ovarian and breast cancer, which may provide an important diagnostic and prognostic marker and will constitute the basis for further study of the role that this protein plays in malignant diseases. In addition, this study suggests that

  10. Evolving landscape of human epidermal growth factor receptor 2-positive breast cancer treatment and the future of biosimilars.

    Science.gov (United States)

    Jackisch, Christian; Lammers, Philip; Jacobs, Ira

    2017-04-01

    Human epidermal growth factor receptor 2-positive (HER2+) breast cancer comprises approximately 15%-20% of all breast cancers and is associated with a poor prognosis. The introduction of anti-HER2 therapy has significantly improved clinical outcomes for patients with HER2+ breast cancer, and multiple HER2-directed agents (ie, trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine [T-DM1]) are approved for clinical use in various settings. The treatment landscape for patients with HER2+ breast cancer is continuing to evolve. While novel agents and therapeutic strategies are emerging, biologic therapies, particularly trastuzumab, are likely to remain a mainstay of treatment. However, access issues create barriers to the use of biologics, and there is evidence for underuse of trastuzumab worldwide. A biosimilar is a biologic product that is highly similar to a licensed biologic in terms of product safety and effectiveness. Biosimilars of trastuzumab are in development and may soon become available. The introduction of biosimilars may improve access to anti-HER2 therapies by providing additional treatment options and lower-cost alternatives. Because HER2-targeted drugs may be administered for extended periods of time and in combination with other systemic therapies, biosimilars have the potential to result in significant savings for healthcare systems. Herein we review current and emerging treatment options for, and discuss the possible role of biosimilars in, treating patients with HER2+ breast cancer. Copyright © 2017 Authors, Pfizer Inc. Published by Elsevier Ltd.. All rights reserved.

  11. Calycosin Inhibits the Migration and Invasion of Human Breast Cancer Cells by Down-Regulation of Foxp3 Expression

    Directory of Open Access Journals (Sweden)

    Shuangxi Li

    2017-12-01

    Full Text Available Background/Aims: Calycosin, a phytoestrogenic compound, has recently emerged as a promising antitumor drug. It has been shown that calycosin suppresses growth and induces apoptosis of breast cancer cells. However, the effect of calycosin on migration and invasion of breast cancer cells and the underlying molecular mechanisms have not been elucidated. Methods: Human breast cancer cells MCF-7 and T47D were treated with, or without, different doses (0, 6.25, 12.5, 25, 50, 100 or 150 μM of calycosin, and the viability of different groups was determined by MTT assay. Next, the inhibitory effect of higher doses (50, 100 or 150 μM of calycosin on migration and invasion of the two cell lines was determined by wound healing and transwell assay. The relative expression levels of forkhead box P3 (Foxp3, vascular endothelial growth factor (VEGF and matrix metalloproteinase-9 (MMP-9 in MCF-7 and T47D cells were determined by quantitative RT-PCR and Western blot. Results: Treatment with lower doses (6.25 or 12.5 μM promoted proliferation of breast cancer cells, but with higher doses significantly reduced the viability of MCF-7 and T47D cells. Furthermore, higher doses of calycosin were found to inhibit migration and invasion of the two cell lines in a dose-dependent manner. Additionally, treatment with a higher dose of calycosin significantly reduced the expression levels of Foxp3, followed by down-regulation of VEGF and MMP-9 in both MCF-7 and T47D breast cancer cells. Conclusion: Treatment with a higher dose of calycosin tends to reduce migration and invasion capacity of human breast cancer cells, by targeting Foxp3-mediated VEGF and MMP-9 expression.

  12. Prognostic impact of placenta growth factor and vascular endothelial growth factor A in patients with breast cancer

    DEFF Research Database (Denmark)

    Maae, Else; Olsen, Dorte Aalund; Dahl Steffensen, Karina

    were measured in 229 tumor tissue specimen from primarily operated patients with unilateral breast cancer. Non-malignant breast tissue was also dissected near the tumor and quantitative measurements were available for 211 patients. PlGF and VEGF-A protein levels in homogenized tissue lysates were...... entered in the model together. Neither PlGF nor VEGF-A expression in non-malignant tissue were predictors for RFS. Conclusion: High protein levels of PlGF and VEGF-A seem to be associated with adverse prognosis in breast cancer patients. Our results support the mutual relationship between PlGF and VEGF......-A and encourage further investigations as prognostic markers in breast cancer patients....

  13. Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies

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    Fedele Vita

    2006-06-01

    Full Text Available Abstract Background Recent studies indicate that microRNAs (miRNAs are mechanistically involved in the development of various human malignancies, suggesting that they represent a promising new class of cancer biomarkers. However, previously reported methods for measuring miRNA expression consume large amounts of tissue, prohibiting high-throughput miRNA profiling from typically small clinical samples such as excision or core needle biopsies of breast or prostate cancer. Here we describe a novel combination of linear amplification and labeling of miRNA for highly sensitive expression microarray profiling requiring only picogram quantities of purified microRNA. Results Comparison of microarray and qRT-PCR measured miRNA levels from two different prostate cancer cell lines showed concordance between the two platforms (Pearson correlation R2 = 0.81; and extension of the amplification, labeling and microarray platform was successfully demonstrated using clinical core and excision biopsy samples from breast and prostate cancer patients. Unsupervised clustering analysis of the prostate biopsy microarrays separated advanced and metastatic prostate cancers from pooled normal prostatic samples and from a non-malignant precursor lesion. Unsupervised clustering of the breast cancer microarrays significantly distinguished ErbB2-positive/ER-negative, ErbB2-positive/ER-positive, and ErbB2-negative/ER-positive breast cancer phenotypes (Fisher exact test, p = 0.03; as well, supervised analysis of these microarray profiles identified distinct miRNA subsets distinguishing ErbB2-positive from ErbB2-negative and ER-positive from ER-negative breast cancers, independent of other clinically important parameters (patient age; tumor size, node status and proliferation index. Conclusion In sum, these findings demonstrate that optimized high-throughput microRNA expression profiling offers novel biomarker identification from typically small clinical samples such as breast

  14. Boswellia sacra essential oil induces tumor cell-specific apoptosis and suppresses tumor aggressiveness in cultured human breast cancer cells

    Science.gov (United States)

    2011-01-01

    Background Gum resins obtained from trees of the Burseraceae family (Boswellia sp.) are important ingredients in incense and perfumes. Extracts prepared from Boswellia sp. gum resins have been shown to possess anti-inflammatory and anti-neoplastic effects. Essential oil prepared by distillation of the gum resin traditionally used for aromatic therapy has also been shown to have tumor cell-specific anti-proliferative and pro-apoptotic activities. The objective of this study was to optimize conditions for preparing Boswellea sacra essential oil with the highest biological activity in inducing tumor cell-specific cytotoxicity and suppressing aggressive tumor phenotypes in human breast cancer cells. Methods Boswellia sacra essential oil was prepared from Omani Hougari grade resins through hydrodistillation at 78 or 100 oC for 12 hours. Chemical compositions were identified by gas chromatography-mass spectrometry; and total boswellic acids contents were quantified by high-performance liquid chromatography. Boswellia sacra essential oil-mediated cell viability and death were studied in established human breast cancer cell lines (T47D, MCF7, MDA-MB-231) and an immortalized normal human breast cell line (MCF10-2A). Apoptosis was assayed by genomic DNA fragmentation. Anti-invasive and anti-multicellular tumor properties were evaluated by cellular network and spheroid formation models, respectively. Western blot analysis was performed to study Boswellia sacra essential oil-regulated proteins involved in apoptosis, signaling pathways, and cell cycle regulation. Results More abundant high molecular weight compounds, including boswellic acids, were present in Boswellia sacra essential oil prepared at 100 oC hydrodistillation. All three human breast cancer cell lines were sensitive to essential oil treatment with reduced cell viability and elevated cell death, whereas the immortalized normal human breast cell line was more resistant to essential oil treatment. Boswellia sacra

  15. A novel human Fab antibody for Trop2 inhibits breast cancer growth in vitro and in vivo.

    Science.gov (United States)

    Lin, Hong; Zhang, Huiling; Wang, Jun; Lu, Meiping; Zheng, Feng; Wang, Changjun; Tang, Xiaojun; Xu, Ning; Chen, Renjie; Zhang, Dawei; Zhao, Ping; Zhu, Jin; Mao, Yuan; Feng, Zhenqing

    2014-03-01

    Human trophoblastic cell surface antigen 2 (Trop2) has been suggested as an oncogene, which is associated with the different types of tumors. In this study, a human Fab antibody against Trop2 extracellular domain was isolated from phage library by phage display technology, and characterized by ELISA, FACS, fluorescence staining and Western blotting analysis. MTT, apoptosis assay and wound healing assay were employed to evaluate the inhibitory effects of Trop2 Fab on breast cancer cell growth in vitro, while tumor-xenograft model was employed to evaluate the inhibitory effects on breast cancer growth in vivo. The results showed that Trop2 Fab inhibited the proliferation, induced the apoptosis and suspended the migration of MDA-MB-231 cells in a dose dependent manner. The expression caspase-3 was activated, and the expression of Bcl-2 was reduced while that of Bax was elevated in MDA-MB-231 cells by treating with Trop2 Fab. In addition, Trop2 Fab inhibited the growth of breast cancer xenografts and the expression of Bcl-2 was reduced while that of Bax was elevated in xenografts. Trop2 Fab, which was isolated successfully in this research, is a promising therapeutic agent for the treatment of Trop2 expressing breast cancer. © 2013 UICC.

  16. FMSP-Nanoparticles Induced Cell Death on Human Breast Adenocarcinoma Cell Line (MCF-7 Cells: Morphometric Analysis

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    Firdos Alam Khan

    2018-05-01

    Full Text Available Currently, breast cancer treatment mostly revolves around radiation therapy and surgical interventions, but often these treatments do not provide satisfactory relief to the patients and cause unmanageable side-effects. Nanomaterials show promising results in treating cancer cells and have many advantages such as high biocompatibility, bioavailability and effective therapeutic capabilities. Interestingly, fluorescent magnetic nanoparticles have been used in many biological and diagnostic applications, but there is no report of use of fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles in the treatment of human breast cancer cells. In the present study, we tested the effect of FMSP-nanoparticles on human breast cancer cells (MCF-7. We tested different concentrations (1.25, 12.5 and 50 µg/mL of FMSP-nanoparticles in MCF-7 cells and evaluated the nanoparticles response morphometrically. Our results revealed that FMSP-nanoparticles produced a concentration dependent effect on the cancer cells, a dose of 1.25 µg/mL produced no significant effect on the cancer cell morphology and cell death, whereas dosages of 12.5 and 50 µg/mL resulted in significant nuclear augmentation, disintegration, chromatic condensation followed by dose dependent cell death. Our results demonstrate that FMSP-nanoparticles induce cell death in MCF-7 cells and may be a potential anti-cancer agent for breast cancer treatment.

  17. Evaluation of Antiproliferative Activity of Red Sorghum Bran Anthocyanin on a Human Breast Cancer Cell Line (MCF-7)

    International Nuclear Information System (INIS)

    Devi, P.S.; Kumar, M.S.; Das, A.S.M.

    2011-01-01

    Breast cancer is a leading cause of death in women worldwide both in the developed and developing countries. Thus effective treatment of breast cancer with potential antitumour drugs is important. In this paper, human breast cancer cell line MCF-7 has been employed to evaluate the antiproliferative activity of red sorghum bran anthocyanin. The present investigation showed that red sorghum bran anthocyanin induced growth inhibition of MCF-7 cells at significant level. The growth inhibition is dose dependent and irreversible in nature. When MCF-7 cells were treated with red sorghum bran anthocyanins due to activity of anthocyanin morphological changes were observed. The morphological changes were identified through the formation of apoptopic bodies. The fragmentation by these anthocyanins on DNA to oligonuleosomal-sized fragments, is a characteristic of apoptosis, and it was observed as concentration-dependent. Thus, this paper clearly demonstrates that human breast cancer cell MCF-7 is highly responsive by red sorghum bran anthocyanins result from the induction of apoptosis in MCF-7 cells.

  18. Detection and quantitation of HER-2/neu gene amplification in human breast cancer archival material using fluorescence in situ hybridization.

    Science.gov (United States)

    Pauletti, G; Godolphin, W; Press, M F; Slamon, D J

    1996-07-04

    Amplification and overexpression of the HER-2/neu gene occurs in 25-30% of human breast cancers. This genetic alteration is associated with a poor clinical prognosis in women with either node negative or node positive breast cancers. The initial studies testing this association were somewhat controversial and this controversy was due in large part to significant heterogeneity in both the methods and/or reagents used in testing archival material for the presence of the alteration. These methods included a number of solid matrix blotting techniques for DNA, RNA and protein as well as immunohistochemistry. Fluorescence in situ hybridization (FISH) represents the newest methodologic approach for testing for this genetic alteration. In this study, FISH is compared to Southern, Northern and Western blot analyses as well as immunohistochemistry in a large cohort of archival human breast cancer specimens. FISH was found to be superior to all other methodologies tested in assessing formalin fixed, paraffin embedded material for HER-2/neu amplification. The results from this study also confirm that overexpression of HER-2/neu rarely occurs in the absence of gene amplification in breast cancer (approximately 3% of cases). This method of analysis is rapid, reproducible and extremely reliable in detecting presence of HER-2/neu gene amplification and should have clinical utility.

  19. Effects of different CMV-heat-inactivation-methods on growth factors in human breast milk.

    Science.gov (United States)

    Goelz, Rangmar; Hihn, Eva; Hamprecht, Klaus; Dietz, Klaus; Jahn, Gerhard; Poets, Christian; Elmlinger, Martin

    2009-04-01

    Preterm infants can inoculate virulent cytomegalovirus (CMV) through their mothers' raw breast milk. Complete virus inactivation is achieved only by heat treatment, but the effect on growth factors has never been assessed systematically. Insulin-like-growth-factor-1-, IGF-2-, insulin-like-growth-factor-binding-protein-2-, and IGFBP-3-concentrations were measured, before and after heating, in 51 breast-milk-samples from 28 mothers, and epidermal-growth-factor-concentrations in a subgroup of 35 samples from 22 mothers. Two heating methods were applied: Short-term (5 s) pasteurisation at 62, 65, and 72 degrees C, and long-term Holder-Pasteurisation (30 min) at 63 degrees C. IGF-1, IGF-2, IGFBP-2, and IGFBP-3 were measured by RIA, and EGF by ELISA. Heating for 30 min decreased significantly IGF-1 by 39.4%, IGF-2 by 9.9%, IGFBP-2 by 19.1%, and IGFBP-3 by 7.0%. In contrast, IGF-1, IGF-2, IGFBP-2, and IGFBP-3 were not altered significantly when using a short heating duration of 5 s, irrespective of the level of temperature, except for IGF-2 at 62 degrees C for 5 s (p = 0.041) and IGFBP-2 at 72 degrees C for 5 s (p = 0.025). Neither long- nor short-time heating methods changed the concentration of EGF. Only short heating methods (5 s, 62-72 degrees C) can preserve, almost completely, the concentrations of IGFs in human milk, whereas Holder-Pasteurization does not.

  20. On-chip immunoelectrophoresis of extracellular vesicles released from human breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Takanori Akagi

    Full Text Available Extracellular vesicles (EVs including exosomes and microvesicles have attracted considerable attention in the fields of cell biology and medicine. For a better understanding of EVs and further exploration of their applications, the development of analytical methods for biological nanovesicles has been required. In particular, considering the heterogeneity of EVs, methods capable of measuring individual vesicles are desired. Here, we report that on-chip immunoelectrophoresis can provide a useful method for the differential protein expression profiling of individual EVs. Electrophoresis experiments were performed on EVs collected from the culture supernatant of MDA-MB-231 human breast cancer cells using a measurement platform comprising a microcapillary electrophoresis chip and a laser dark-field microimaging system. The zeta potential distribution of EVs that reacted with an anti-human CD63 (exosome and microvesicle marker antibody showed a marked positive shift as compared with that for the normal immunoglobulin G (IgG isotype control. Thus, on-chip immunoelectrophoresis could sensitively detect the over-expression of CD63 glycoproteins on EVs. Moreover, to explore the applicability of on-chip immunoelectrophoresis to cancer diagnosis, EVs collected from the blood of a mouse tumor model were analyzed by this method. By comparing the zeta potential distributions of EVs after their immunochemical reaction with normal IgG, and the anti-human CD63 and anti-human CD44 (cancer stem cell marker antibodies, EVs of tumor origin circulating in blood were differentially detected in the real sample. The result indicates that the present method is potentially applicable to liquid biopsy, a promising approach to the low-invasive diagnosis of cancer.

  1. Soluble CD14 in human breast milk and its role in innate immune responses.

    Science.gov (United States)

    Vidal, K; Labéta, M O; Schiffrin, E J; Donnet-Hughes, A

    2001-10-01

    Immune factors secreted in milk are important for health in the neonatal gut. We have detected the bacterial pattern recognition receptor, soluble CD14 (sCD14) in human breast milk at different times during lactation. The molecule occurs in a single form in milk, in contrast to human serum, in which there are two isoforms. Produced by mammary epithelial cells, milk sCD14 mediates secretion of innate immune response molecules such as interleukin-8, tumor necrosis factor-alpha, and epithelial neutrophil activator-78 by CD14-negative intestinal epithelial cells exposed to lipopolysaccharide (LPS) or bacteria. Although present at low concentrations in milk, LPS-binding protein may be implicated in the biological effects observed. Our findings support the premise that milk sCD14 acts as a 'sentinel' molecule and immune modulator in homeostasis and in the defense of the neonatal intestine. In so doing, it may prevent the immune and inflammatory conditions of the gut to which non-breastfed infants are predisposed.

  2. Human Listeriosis Presenting as Breast Abscess: Report of a Rare Case.

    Science.gov (United States)

    Kandi, Venkataramana

    2017-02-01

    An abscess is defined as a collection of pus in various tissues of the body including skin and other organs. Abscesses most commonly are formed on the skin under the armpits, groin areas, and rectal areas. Most abscesses involve microbial infections with few remaining sterile. The treatment of abscesses includes both medical and surgical intervention. In the era of multidrug resistance, isolation and identification of the causative microbe and testing for antimicrobial susceptible patterns assume greater significance for the better management of patients, thereby reducing the resultant morbidity and mortality. Listeria spp. are a group of aerobic and non-spore forming gram-positive bacilli. They are present in the environment, soil, and water. Listeria spp. have also been noted to be present as a normal intestinal flora of animals. They are known for their ability to thrive under both cold and hot environmental conditions. Human infections with Listeria spp. have not been frequently reported, mostly because of the difficulty in laboratory identification and complex clinical presentations. In humans, Listeria spp. have been frequently responsible for food poisoning and neonatal meningitis. Although not considered as a classic pathogen, Listeria spp. are associated with infections in elderly people, pregnant women, newborns, and persons with weakened immune systems. This report presents a case of breast abscess caused by Listeria spp. in a young lactating female belonging to rural India.

  3. Effects of extracellular modulation through hypoxia on the glucose metabolism of human breast cancer stem cells

    Science.gov (United States)

    Yustisia, I.; Jusman, S. W. A.; Wanandi, S. I.

    2017-08-01

    Cancer stem cells have been reported to maintain stemness under certain extracellular changes. This study aimed to analyze the effect of extracellular O2 level modulation on the glucose metabolism of human CD24-/CD44+ breast cancer stem cells (BCSCs). The primary BCSCs (CD24-/CD44+ cells) were cultured under hypoxia (1% O2) for 0.5, 4, 6, 24 and 48 hours. After each incubation period, HIF1α, GLUT1 and CA9 expressions, as well as glucose metabolism status, including glucose consumption, lactate production, O2 consumption and extracellular pH (pHe) were analyzed using qRT-PCR, colorimetry, fluorometry, and enzymatic reactions, respectively. Hypoxia caused an increase in HIF1α mRNA expressions and protein levels and shifted the metabolic states to anaerobic glycolysis, as demonstrated by increased glucose consumption and lactate production, as well as decreased O2 consumption and pHe. Furthermore, we demonstrated that GLUT1 and CA9 mRNA expressions simultaneously increased, in line with HIF1α expression. In conclusion, modulation of the extracellular environment of human BCSCs through hypoxia shifedt the metabolic state of BCSCs to anaerobic glycolysis, which might be associated with GLUT1 and CA9 expressions regulated by HIFlα transcription factor.

  4. 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

  5. Enhanced and Selective Antiproliferative Activity of Methotrexate-Functionalized-Nanocapsules to Human Breast Cancer Cells (MCF-7

    Directory of Open Access Journals (Sweden)

    Catiúscia P. de Oliveira

    2018-01-01

    Full Text Available Methotrexate is a folic acid antagonist and its incorporation into nanoformulations is a promising strategy to increase the drug antiproliferative effect on human breast cancer cells by overexpressing folate receptors. To evaluate the efficiency and selectivity of nanoformulations containing methotrexate and its diethyl ester derivative, using two mechanisms of drug incorporation (encapsulation and surface functionalization in the in vitro cellular uptake and antiproliferative activity in non-tumoral immortalized human keratinocytes (HaCaT and in human breast carcinoma cells (MCF-7. Methotrexate and its diethyl ester derivative were incorporated into multiwall lipid-core nanocapsules with hydrodynamic diameters lower than 160 nm and higher drug incorporation efficiency. The nanoformulations were applied to semiconfluent HaCaT or MCF-7 cells. After 24 h, the nanocapsules were internalized into HaCaT and MCF-7 cells; however, no significant difference was observed between the nanoformulations in HaCaT (low expression of folate receptors, while they showed significantly higher cellular uptakes than the blank-nanoformulation in MCF-7, which was the highest uptakes observed for the drug functionalized-nanocapsules. No antiproliferative activity was observed in HaCaT culture, whereas drug-containing nanoformulations showed antiproliferative activity against MCF-7 cells. The effect was higher for drug-surface functionalized nanocapsules. In conclusion, methotrexate-functionalized-nanocapsules showed enhanced and selective antiproliferative activity to human breast cancer cells (MCF-7 being promising products for further in vivo pre-clinical evaluations.

  6. A short synthetic peptide fragment of human C2ORF40 has therapeutic potential in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chaoyang [Shandong Univ., Jinan (China); Zhang, Pengju [Shandong Univ., Jinan (China); Jiang, Anli [Shandong Univ., Jinan (China); Mao, Jian-Hua [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Wei, Guangwei [Shandong Univ. School of Medicine, Jinan (China)

    2017-03-30

    C2ORF40 encodes a secreted protein which is cleaved to generate soluble peptides by proteolytic processing and this process is believed to be necessary for C2ORF40 to exert cell type specific biological activity. Here, we reported a short mimic peptide of human C2ORF40 acts potential therapeutic efficacy in human cancer cells in vitro and in vivo. We synthesized a short peptide of human C2ORF40, named C2ORF40 mimic peptide fragment and assessed its biological function on cancer cell growth, migration and tumorigenesis. Cell growth assay showed that C2ORF40 mimic peptide fragment significantly suppressed cell proliferation of breast and lung cancer cells. Moreover, C2ORF40 mimic peptide fragment significantly inhibited the migration and invasion of breast cancer cells. Furthermore, we showed that this peptide suppressed tumorigenesis in breast tumor xenograft model. Cell cycle assay indicated that the C2ORF40 mimic peptide fragment suppressed the growth of tumor cells through inducing mitotic phase arrest. In conclusion, our results firstly suggested that this short synthetic peptide of human C2ORF40 may be a candidate tumor therapeutic agent.

  7. lacZ transduced human breast cancer xenografts as an in vivo model for the study of invasion and metastasis

    DEFF Research Database (Denmark)

    Brünner, N; Thompson, E W; Spang-Thomsen, M

    1992-01-01

    in the animals by usual histological procedures would require extensive sectioning of the whole animal. To overcome this problem, we transduced human breast cancer cells with a replication-defective Moloney murine leukaemia retroviral vector (M-MuLV) containing both neoR (neomycin resistance) and lacZ genes...... but not the surrounding mouse tissue on either whole tissue blocks or histological sections. The staining procedure was highly sensitive, allowing detection of microfoci of human cancer cells, and quantitative estimation of the metastatic capacity of the cells. These results indicate that lacZ transduction of human...

  8. Expression of integrin α3β1 and cyclooxygenase-2 (COX2) are positively correlated in human breast cancer

    International Nuclear Information System (INIS)

    Aggarwal, Anshu; Al-Rohil, Rami N; Batra, Anupam; Feustel, Paul J; Jones, David M; DiPersio, C Michael

    2014-01-01

    Expression of integrin α3β1 is associated with tumor progression, metastasis, and poor prognosis in several cancers, including breast cancer. Moreover, preclinical studies have revealed important pro-tumorigenic and pro-metastatic functions for this integrin, including tumor growth, survival, invasion, and paracrine induction of angiogenesis. Our previously published work in a preclinical breast cancer model showed that integrin α3β1 promotes expression of cyclooxygenase-2 (COX2/PTGS2), a known driver of breast cancer progression. However, the clinical significance of this regulation was unknown. The objective of the current study was to assess the clinical relevance of the relationship between integrin α3β1 and COX2 by testing for their correlated expression among various forms of human breast cancer. Immunohistochemistry was performed to assess co-expression of α3 and COX2 in specimens of human invasive ductal carcinoma (IDC), either on a commercial tissue microarray (n = 59 samples) or obtained from Albany Medical Center archives (n = 68 samples). Immunostaining intensity for the integrin α3 subunit or COX2 was scored, and Spearman’s rank correlation coefficient analysis was performed to assess their co-expression across and within different tumor subtypes or clinicopathologic criteria. Although expression of integrin α3 or COX2 varied among clinical IDC samples, a statistically significant, positive correlation was detected between α3 and COX2 in both tissue microarrays (r s = 0.49, p < 0.001, n = 59) and archived samples (r s = 0.59, p < 0.0001, n = 68). In both sample sets, this correlation was independent of hormone receptor status, histological grade, or disease stage. COX2 and α3 are correlated in IDC independently of hormone receptor status or other clinicopathologic features, supporting the hypothesis that integrin α3β1 is a determinant of COX2 expression in human breast cancer. These results support the clinical relevance of α3β1

  9. Amplexicaule A exerts anti-tumor effects by inducing apoptosis in human breast cancer

    OpenAIRE

    Xiang, Meixian; Su, Hanwen; Shu, Guangwen; Wan, Dingrong; He, Feng; Loaec, Morgann; Ding, Yali; Li, Jun; Dovat, Sinisa; Yang, Gaungzhong; Song, Chunhua

    2016-01-01

    Chemotherapy is the main treatment for patients with breast cancer metastases, but natural alternatives have been receiving attention for their potential as novel anti-tumor reagents. Amplexicaule A (APA) is a flavonoid glucoside isolated from rhizomes of Polygonum amplexicaule D. Don var. sinense Forb (PADF). We found that APA has anti-tumor effects in a breast cancer xenograft mouse model and induces apoptosis in breast cancer cell lines. APA increased levels of cleaved caspase-3,-8,-9 and ...

  10. Oncogenic Viruses and Breast Cancer: Mouse Mammary Tumor Virus (MMTV), Bovine Leukemia Virus (BLV), Human Papilloma Virus (HPV), and Epstein-Barr Virus (EBV).

    Science.gov (United States)

    Lawson, James S; Salmons, Brian; Glenn, Wendy K

    2018-01-01

    Although the risk factors for breast cancer are well established, namely female gender, early menarche and late menopause plus the protective influence of early pregnancy, the underlying causes of breast cancer remain unknown. The development of substantial recent evidence indicates that a handful of viruses may have a role in breast cancer. These viruses are mouse mammary tumor virus (MMTV), bovine leukemia virus (BLV), human papilloma viruses (HPVs), and Epstein-Barr virus (EBV-also known as human herpes virus type 4). Each of these viruses has documented oncogenic potential. The aim of this review is to inform the scientific and general community about this recent evidence. MMTV and human breast cancer-the evidence is detailed and comprehensive but cannot be regarded as conclusive. BLV and human breast cancer-the evidence is limited. However, in view of the emerging information about BLV in human breast cancer, it is prudent to encourage the elimination of BLV in cattle, particularly in the dairy industry. HPVs and breast cancer-the evidence is substantial but not conclusive. The availability of effective preventive vaccines is a major advantage and their use should be encouraged. EBV and breast cancer-the evidence is also substantial but not conclusive. Currently, there are no practical means of either prevention or treatment. Although there is evidence of genetic predisposition, and cancer in general is a culmination of events, there is no evidence that inherited genetic traits are causal. The influence of oncogenic viruses is currently the major plausible hypothesis for a direct cause of human breast cancer.

  11. Oncogenic Viruses and Breast Cancer: Mouse Mammary Tumor Virus (MMTV, Bovine Leukemia Virus (BLV, Human Papilloma Virus (HPV, and Epstein–Barr Virus (EBV

    Directory of Open Access Journals (Sweden)

    James S. Lawson

    2018-01-01

    Full Text Available BackgroundAlthough the risk factors for breast cancer are well established, namely female gender, early menarche and late menopause plus the protective influence of early pregnancy, the underlying causes of breast cancer remain unknown. The development of substantial recent evidence indicates that a handful of viruses may have a role in breast cancer. These viruses are mouse mammary tumor virus (MMTV, bovine leukemia virus (BLV, human papilloma viruses (HPVs, and Epstein–Barr virus (EBV-also known as human herpes virus type 4. Each of these viruses has documented oncogenic potential. The aim of this review is to inform the scientific and general community about this recent evidence.The evidenceMMTV and human breast cancer—the evidence is detailed and comprehensive but cannot be regarded as conclusive. BLV and human breast cancer—the evidence is limited. However, in view of the emerging information about BLV in human breast cancer, it is prudent to encourage the elimination of BLV in cattle, particularly in the dairy industry. HPVs and breast cancer—the evidence is substantial but not conclusive. The availability of effective preventive vaccines is a major advantage and their use should be encouraged. EBV and breast cancer—the evidence is also substantial but not conclusive. Currently, there are no practical means of either prevention or treatment. Although there is evidence of genetic predisposition, and cancer in general is a culmination of events, there is no evidence that inherited genetic traits are causal.ConclusionThe influence of oncogenic viruses is currently the major plausible hypothesis for a direct cause of human breast cancer.

  12. Multiplex Quantitative Histologic Analysis of Human Breast Cancer Cell Signaling and Cell Fate

    National Research Council Canada - National Science Library

    Lee, William M; Roysam, Badrinath

    2008-01-01

    .... We are developing a novel platform for immunohistological study of breast cancer specimens that will retrieve multiplex quantitative molecular information about tumor cells at a cytologic level...

  13. Applicability of active infrared thermography for screening of human breast: a numerical study

    Science.gov (United States)

    Dua, Geetika; Mulaveesala, Ravibabu

    2018-03-01

    Active infrared thermography is a fast, painless, noncontact, and noninvasive imaging method, complementary to mammography, ultrasound, and magnetic resonance imaging methods for early diagnosis of breast cancer. This technique plays an important role in early detection of breast cancer to women of all ages, including pregnant or nursing women, with different sizes of breast, irrespective of either fatty or dense breast. This proposed complementary technique makes use of infrared emission emanating from the breast. Emanating radiations from the surface of the breast under test are detected with an infrared camera to map the thermal gradients over it, in order to reveal hidden tumors inside it. One of the reliable active infrared thermographic technique, linear frequency modulated thermal wave imaging is adopted to detect tumors present inside the breast. Further, phase and amplitude images are constructed using frequency and time-domain data analysis schemes. Obtained results show the potential of the proposed technique for early diagnosis of breast cancer in fatty as well as dense breasts.

  14. PIEZO channel protein naturally expressed in human breast cancer cell MDA-MB-231 as probed by atomic force microscopy

    Science.gov (United States)

    Weng, Yuanqi; Yan, Fei; Chen, Runkang; Qian, Ming; Ou, Yun; Xie, Shuhong; Zheng, Hairong; Li, Jiangyu

    2018-05-01

    Mechanical stimuli drives many physiological processes through mechanically activated channels, and the recent discovery of PIEZO channel has generated great interests in its mechanotransduction. Many previous researches investigated PIEZO proteins by transcribing them in cells that originally have no response to mechanical stimulation, or by forming PIEZO-combined complexes in vitro, and few studied PIEZO protein's natural characteristics in cells. In this study we show that MDA-MB-231, a malignant cell in human breast cancer cell line, expresses the mechanosensitive behavior of PIEZO in nature without extra treatment, and we report its characteristics in response to localized mechanical stimulation under an atomic force microscope, wherein a correlation between the force magnitude applied and the channel opening probability is observed. The results on PIEZO of MDA-MB-231 can help establish a basis of preventing and controlling of human breast cancer cell via mechanical forces.

  15. Evaluation of probiotic properties of Lactobacillus plantarum WLPL04 isolated from human breast milk.

    Science.gov (United States)

    Jiang, Meiling; Zhang, Fen; Wan, Cuixiang; Xiong, Yonghua; Shah, Nagendra P; Wei, Hua; Tao, Xueying

    2016-03-01

    Lactobacillus plantarum WLPL04, a specific strain isolated from human breast milk, was investigated for its survival capacity (acid and bile salt tolerance, survival in simulated gastrointestinal tract, inhibition of pathogens, antibiotic susceptibility, yield of exopolysaccharides) and probiotic properties (antiadhesion of pathogens, protection from harmful effect of sodium dodecyl sulfate, and antiinflammatory stress on Caco-2 cells). The results showed that Lb. plantarum WLPL04 had broad-spectrum activity against gram-positive strains (Listeria monocytogenes CMCC54007, Bacillus cereus ATCC14579, and Staphylococcus aureus CMCC26003) and gram-negative strains (Pseudomonas aeruginosa MCC10104, Shigella sonnei ATCC25931, Enterobacter sakazakii ATCC29544, Salmonella typhimurium ATCC13311, and Escherichia coli O157:H7). Antibiotic susceptibility tests showed that Lb. plantarum WLPL04 was susceptible to 8 of 14 antibiotics (e.g., erythromycin and nitrofurantoin) and resistant to 6 of 14 antibiotics (e.g., kanamycin and bacitracin). Lactobacillus plantarum WLPL04 was able to survive at pH 2.5 for 3h and at 0.45% bile salt for 12h, suggesting that it can survive well in the gastrointestinal tract. In addition, the exopolysaccharide yield of Lb. plantarum WLPL04 reached 426.73 ± 65.56 mg/L at 24h. With strategies of competition, inhibition, and displacement, Lb. plantarum WLPL04 reduced the adhesion of E. coli O157:H7 (35.51%), Sal. typhimurium ATCC 13311 (8.10%), and Staph. aureus CMCC 26003 (40.30%) on Caco-2 cells by competition, and subsequently by 59.80, 62.50, and 42.60%, respectively, for the 3 pathogens through inhibition, and by 75.23, 39.97, and 52.88%, respectively, through displacement. Lactobacillus plantarum WLPL04 attenuated the acute stress induced by sodium dodecyl sulfate on Caco-2 cells and significantly inhibited the expression of inflammatory cytokines (IL-6, IL-8 and tumor necrosis factor-α) on Caco-2 cells but increased IL-10 expression in vitro

  16. The Norwegian human milk study HUMIS variations in levels of chlorinated pesticides, PCBs and PBDEs in Norwegian breast milk

    Energy Technology Data Exchange (ETDEWEB)

    Polder, A.; Loeken, K. [The Norwegian School of Veterinary Science, Oslo (Norway); Thomsen, C.; Becher, G.; Eggesboe, M. [Norwegian Inst. of Public Health, Oslo (Norway); Skaare, J.U. [National Veterinary Inst., Oslo (Norway)

    2004-09-15

    Organochlorine pesticides (OCPs), polychlorinated, -dibenzo-pdioxins (PCDDs), -dibenzofurans (PCDFs), -biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are among the persistent organic pollutants (POPs) that have been found to accumulate in human breast milk. Because nursing children are exposed to these chemicals through the contaminated breast milk, health authorities worldwide are concerned for the infants' intake and therefore human milk monitoring programs are performed in many countries. While restrictions and bans resulted in a decline of organochlorines (OCs) in human milk during the last decades, an increasing trend has been found for PBDEs. The main goals of ''The Norwegian Human Milk Study, HUMIS'' are: to elucidate the human exposure in Norway to POPs, to identify dietary habits and other lifestyle factors that are associated with high levels of POPs in human milk, and to study the impact of exposure to the these contaminants on child health. This study reports preliminary results of recent levels of POPs in human milk in 4 different counties in Norway.

  17. Human Breast Milk and Infant Formulas Differentially Modify the Intestinal Microbiota in Human Infants and Host Physiology in Rats.

    Science.gov (United States)

    Liu, Zhenmin; Roy, Nicole C; Guo, Yanhong; Jia, Hongxin; Ryan, Leigh; Samuelsson, Linda; Thomas, Ancy; Plowman, Jeff; Clerens, Stefan; Day, Li; Young, Wayne

    2016-02-01

    In the absence of human breast milk, infant and follow-on formulas can still promote efficient growth and development. However, infant formulas can differ in their nutritional value. The objective of this study was to compare the effects of human milk (HM) and infant formulas in human infants and a weanling rat model. In a 3 wk clinical randomized controlled trial, babies (7- to 90-d-old, male-to-female ratio 1:1) were exclusively breastfed (BF), exclusively fed Synlait Pure Canterbury Stage 1 infant formula (SPCF), or fed assorted standard formulas (SFs) purchased by their parents. We also compared feeding HM or SPCF in weanling male Sprague-Dawley rats for 28 d. We examined the effects of HM and infant formulas on fecal short chain fatty acids (SCFAs) and bacterial composition in human infants, and intestinal SCFAs, the microbiota, and host physiology in weanling rats. Fecal Bifidobacterium concentrations (mean log copy number ± SEM) were higher (P = 0.003) in BF (8.17 ± 0.3) and SPCF-fed infants (8.29 ± 0.3) compared with those fed the SFs (6.94 ± 0.3). Fecal acetic acid (mean ± SEM) was also higher (P = 0.007) in the BF (5.5 ± 0.2 mg/g) and SPCF (5.3 ± 2.4 mg/g) groups compared with SF-fed babies (4.3 ± 0.2 mg/g). Colonic SCFAs did not differ between HM- and SPCF-fed rats. However, cecal acetic acid concentrations were higher (P = 0.001) in rats fed HM (42.6 ± 2.6 mg/g) than in those fed SPCF (30.6 ± 0.8 mg/g). Cecal transcriptome, proteome, and plasma metabolite analyses indicated that the growth and maturation of intestinal tissue was more highly promoted by HM than SPCF. Fecal bacterial composition and SCFA concentrations were similar in babies fed SPCF or HM. However, results from the rat study showed substantial differences in host physiology between rats fed HM and SPCF. This trial was registered at Shanghai Jiào tong University School of Medicine as XHEC-C-2012-024. © 2016 American Society for Nutrition.

  18. Antitumor Activity of Chinese Propolis in Human Breast Cancer MCF-7 and MDA-MB-231 Cells

    Directory of Open Access Journals (Sweden)

    Hongzhuan Xuan

    2014-01-01

    Full Text Available Chinese propolis has been reported to possess various biological activities such as antitumor. In present study, anticancer activity of ethanol extract of Chinese propolis (EECP at 25, 50, 100, and 200 μg/mL was explored by testing the cytotoxicity in MCF-7 (human breast cancer ER(+ and MDA-MB-231 (human breast cancer ER(− cells. EECP revealed a dose- and time-dependent cytotoxic effect. Furthermore, annexin A7 (ANXA7, p53, nuclear factor-κB p65 (NF-κB p65, reactive oxygen species (ROS levels, and mitochondrial membrane potential were investigated. Our data indicated that treatment of EECP for 24 and 48 h induced both cells apoptosis obviously. Exposure to EECP significantly increased ANXA7 expression and ROS level, and NF-κB p65 level and mitochondrial membrane potential were depressed by EECP dramatically. The effects of EECP on p53 level were different in MCF-7 and MDA-MB-231 cells, which indicated that EECP exerted its antitumor effects in MCF-7 and MDA-MB-231 cells by inducing apoptosis, regulating the levels of ANXA7, p53, and NF-κB p65, upregulating intracellular ROS, and decreasing mitochondrial membrane potential. Interestingly, EECP had little or small cytotoxicity on normal human umbilical vein endothelial cells (HUVECs. These results suggest that EECP is a potential alternative agent on breast cancer treatment.

  19. Poly(ADP-ribose polymerase 1 (PARP1 overexpression in human breast cancer stem cells and resistance to olaparib.

    Directory of Open Access Journals (Sweden)

    Marine Gilabert

    Full Text Available BACKGROUND: Breast cancer stem cells (BCSCs have been recognized as playing a major role in various aspects of breast cancer biology. To identify specific biomarkers of BCSCs, we have performed comparative proteomics of BCSC-enriched and mature cancer cell populations from the human breast cancer cell line (BCL, BrCA-MZ-01. METHODS: ALDEFLUOR assay was used to sort BCSC-enriched (ALDH+ and mature cancer (ALDH- cell populations. Total proteins were extracted from both fractions and subjected to 2-Dimensional Difference In-Gel Electrophoresis (2-D DIGE. Differentially-expressed spots were excised and proteins were gel-extracted, digested and identified using MALDI-TOF MS. RESULTS: 2-D DIGE identified poly(ADP-ribose polymerase 1 (PARP1 as overexpressed in ALDH+ cells from BrCA-MZ-01. This observation was confirmed by western blot and extended to four additional human BCLs. ALDH+ cells from BRCA1-mutated HCC1937, which had the highest level of PARP1 overexpression, displayed resistance to olaparib, a specific PARP1 inhibitor. CONCLUSION: An unbiased proteomic approach identified PARP1 as upregulated in ALDH+, BCSC-enriched cells from various human BCLs, which may contribute to clinical resistance to PARP inhibitors.

  20. Human murine mammary tumour virus-like agents are genetically distinct from endogenous retroviruses and are not detectable in breast cancer cell lines or biopsies

    International Nuclear Information System (INIS)

    Mant, Christine; Gillett, Cheryl; D'Arrigo, Corrado; Cason, John

    2004-01-01

    It has been reported that a human murine mammary tumour virus (MMTV)-like virus (HMLV), which may be an endogenous human retrovirus (HERV), occurs in the human breast cancer cell lines T47D and MCF-7 and, in 38% of human breast cancer biopsies. As the aetiology of most breast cancers remains unknown, it is important to verify these observations in differing breast cancer populations worldwide. Thus, we sought to determine the genetic relationships between HMLVs, MMTVs, and HERVs, and to investigate the association between HMLVs and breast cancer biopsies from South London, UK. Phylogenetic analyses of the env/pol region indicated that HMLVs are indistinct from MMTVs, and that MMTVS/HMLVs exhibit only low sequence homologies with HERVs. A search of the human genome confirmed that HMLVs are not endogenous. Using MMTV polymerase chain reaction (PCR) primers described previously, we amplified DNA from all cell lines except MCF-7 and from 7 of 44 (16%) breast cancer biopsies. A restriction fragment length polymorphism assay was designed to distinguish between HMLVs and MMTVs, and upon analyses, PCR amplicons appeared to be HMLVs. To confirm these findings, amplicons from the T47D cell line and from four randomly selected breast cancer patients were sequenced. Of 106 DNA sequences obtained, 103 were homologous with a short arm of human chromosome (Chr) 3 (3p13), two with Chr 4, and one with Chr 8. None of the sequences exhibited significant nucleotide homology with MMTVs, HMLVs, or with HERVs (all <50%). Thus, we conclude that (i) HMLVs are integral members of the MMTV family; (ii) MMTVs/HMLVs are genetically distinct from HERVs; (iii) MMTV/HMLV DNA is not present in human breast cancer cell lines or clinical biopsies in our locality

  1. Kiss-1/GPR54 protein expression in breast cancer.

    Science.gov (United States)

    Papaoiconomou, Eleni; Lymperi, Maria; Petraki, Constantina; Philippou, Anastassios; Msaouel, Pavlos; Michalopoulou, Fani; Kafiri, Georgia; Vassilakos, George; Zografos, Georgios; Koutsilieris, Michael

    2014-03-01

    Numerous studies have shown that the Kiss-1 gene countervails the metastatic aptitude of several cancer cell lines and solid-tumor neoplasias. However, there still remains ambiguity regarding its role in breast cancer and literature has arisen asserting that Kiss-1 expression may be linked to an aggressive phenotype and malignant progression. Herein, we investigated the protein expression of Kiss-1 and its receptor GPR54 in breast cancer tissues compared to non-cancerous mammary tissues. Paraffin-fixed cancer tissues from 43 women with resected breast adenocarcinomas and 11 specimens derived from women suffering from fibrocystic disease, serving as controls, were immunostained with Kiss-1 and GPR54 antibodies. Kiss-1 and GPR54 protein expression levels were significantly higher in breast cancer compared to fibrocystic tissues (pbreast cancer and fibrocystic disease specimens. Kiss-1/GPR54 expression was found to be significantly higher in breast cancer compared to non-malignant mammary tissues.

  2. A Comprehensive Evaluation Of HER-2/NEU In Human Breast Cancer By Immunohistochemistry And Fluorescence In Situ Hybridization

    International Nuclear Information System (INIS)

    Abdel Fattah, H.I.; Seif, A.A.; El Hadidi, E.S.; Mohamed, A.A.; El Shinawi, M.E.; Shabaan, M.A.M.

    2012-01-01

    Background: Accurate diagnostic assessment of human epidermal growth factor receptor-2 (HER2/neu) is essential and a prerequisite for appropriate application of the humanized anti-HER-2 monoclonal antibody trastuzumab (Herceptin) to the treatment of patients with breast cancer. The food drug administration (FDA) approved immunohistochemistry (IHC) and Fluorescence in situ hybridization (FISH) for HER2/neu evaluation. IHC is the most widely applicable diagnostic modality in studying HER-2 status. FISH is used for HER2/neu assessment in cases with an equivocal IHC status (score 2+). Objectives: The aim of this study was to detect the amplification and/or expression of HER2/neu in breast cancer using FISH and IHC techniques and to evaluate these applied techniques for their potential and clinical application, with special consideration of equivocal cases by IHC (2+). Subjects and Methods: Assessment of HER2/neu gene expression was made by FISH analysis using the HER2/CEP dual color probe (Vysis) in paraffin-embedded tissue sections of 32 breast cancer patients who were grouped into stages 1+, 2+ or 3+ based on IHC (CBII monoclonal antibody), 4 were classified as IHC 0, 4 were classified as IHC 1 +, 22 were classified as the borderline group; IHC 2+, and 2 were classified as IHC 3+. ER, PR, CEA and CA15-3 were performed to all cases. Survival data was obtained from 25 patients only. Results: The cut-off suggested for HER2/neu amplification by FISH ratio was > 1.3. No statistical significance was found between HER2/neu -by either FISH or IHC- and the different prognostic parameters. The overall survival for the studied patients -in average 3 years- was 16/25 (64%). A significant statistical association was revealed between breast cancer patients’ survival outcome and HER2/neu amplification (p < 0.05) using chi square test. Conclusion: All breast cancer patients should be assessed for HER2/neu status. IHC is a well established method for assessing HER2/neu status in

  3. Calcitriol inhibits Ether-a go-go potassium channel expression and cell proliferation in human breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Becerra, Rocio [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Diaz, Lorenza, E-mail: lorenzadiaz@gmail.com [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Camacho, Javier [Department of Pharmacology, Centro de Investigacion y de Estudios Avanzados, Instituto Politecnico Nacional, Av. Instituto Politecnico Nacional 2508, San Pedro Zacatenco 07360, Mexico, D.F. (Mexico); Barrera, David; Ordaz-Rosado, David; Morales, Angelica [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Ortiz, Cindy Sharon [Department of Pathology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Avila, Euclides [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Bargallo, Enrique [Department of Breast Tumors, Instituto Nacional de Cancerologia, Av. San Fernando No. 22, Tlalpan 14080, Mexico, D.F. (Mexico); Arrecillas, Myrna [Department of Pathology, Instituto Nacional de Cancerologia, Av. San Fernando No. 22, Tlalpan 14080, Mexico, D.F. (Mexico); Halhali, Ali; Larrea, Fernando [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico)

    2010-02-01

    Antiproliferative actions of calcitriol have been shown to occur in many cell types; however, little is known regarding the molecular basis of this process in breast carcinoma. Ether-a-go-go (Eag1) potassium channels promote oncogenesis and are implicated in breast cancer cell proliferation. Since calcitriol displays antineoplastic effects while Eag1 promotes tumorigenesis, and both factors antagonically regulate cell cycle progression, we investigated a possible regulatory effect of calcitriol upon Eag1 as a mean to uncover new molecular events involved in the antiproliferative activity of this hormone in human breast tumor-derived cells. RT real-time PCR and immunocytochemistry showed that calcitriol suppressed Eag1 expression by a vitamin D receptor (VDR)-dependent mechanism. This effect was accompanied by inhibition of cell proliferation, which was potentiated by astemizole, a nonspecific Eag1 inhibitor. Immunohistochemistry and Western blot demonstrated that Eag1 and VDR abundance was higher in invasive-ductal carcinoma than in fibroadenoma, and immunoreactivity of both proteins was located in ductal epithelial cells. Our results provide evidence of a novel mechanism involved in the antiproliferative effects of calcitriol and highlight VDR as a cancer therapeutic target for breast cancer treatment and prevention.

  4. Alpha cyano-4-hydroxy-3-methoxycinnamic acid inhibits proliferation and induces apoptosis in human breast cancer cells.

    Science.gov (United States)

    Hamdan, Lamia; Arrar, Zoheir; Al Muataz, Yacoub; Suleiman, Lutfi; Négrier, Claude; Mulengi, Joseph Kajima; Boukerche, Habib

    2013-01-01

    This study investigated the underlying mechanism of 4-hydroxy-3-methoxycinnamic acid (ACCA), on the growth of breast cancer cells and normal immortal epithelial cells, and compared their cytotoxic effects responses. Treatment of breast cancer cells (MCF-7, T47D, and MDA-231) with ACCA resulted in dose- and time-dependent decrease of cell proliferation, viability in colony formation assay, and programmed cell death (apoptosis) with minimal effects on non-tumoral cells. The ability of ACCA to suppress growth in cancer cells not expressing or containing defects in p53 gene indicates a lack of involvement of this critical tumor suppressor element in mediating ACCA-induced growth inhibition. Induction of apoptosis correlated with an increase in Bax protein, an established inducer of programmed cell death, and the ratio of Bax to Bcl-2, an established inhibitor of apoptosis. We also documented the ability of ACCA to inhibit the migration and invasion of MDA-231 cells with ACCA in vitro. Additionally, tumor growth of MDA-231 breast cancer cells in vivo was dramatically affected with ACCA. On the basis of its selective anticancer inhibitory activity on tumor cells, ACCA may represent a promising therapeutic drug that should be further evaluated as a chemotherapeutic agent for human breast cancer.

  5. Alpha cyano-4-hydroxy-3-methoxycinnamic acid inhibits proliferation and induces apoptosis in human breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Lamia Hamdan

    Full Text Available This study investigated the underlying mechanism of 4-hydroxy-3-methoxycinnamic acid (ACCA, on the growth of breast cancer cells and normal immortal epithelial cells, and compared their cytotoxic effects responses. Treatment of breast cancer cells (MCF-7, T47D, and MDA-231 with ACCA resulted in dose- and time-dependent decrease of cell proliferation, viability in colony formation assay, and programmed cell death (apoptosis with minimal effects on non-tumoral cells. The ability of ACCA to suppress growth in cancer cells not expressing or containing defects in p53 gene indicates a lack of involvement of this critical tumor suppressor element in mediating ACCA-induced growth inhibition. Induction of apoptosis correlated with an increase in Bax protein, an established inducer of programmed cell death, and the ratio of Bax to Bcl-2, an established inhibitor of apoptosis. We also documented the ability of ACCA to inhibit the migration and invasion of MDA-231 cells with ACCA in vitro. Additionally, tumor growth of MDA-231 breast cancer cells in vivo was dramatically affected with ACCA. On the basis of its selective anticancer inhibitory activity on tumor cells, ACCA may represent a promising therapeutic drug that should be further evaluated as a chemotherapeutic agent for human breast cancer.

  6. Calcitriol inhibits Ether-a go-go potassium channel expression and cell proliferation in human breast cancer cells

    International Nuclear Information System (INIS)

    Garcia-Becerra, Rocio; Diaz, Lorenza; Camacho, Javier; Barrera, David; Ordaz-Rosado, David; Morales, Angelica; Ortiz, Cindy Sharon; Avila, Euclides; Bargallo, Enrique; Arrecillas, Myrna; Halhali, Ali; Larrea, Fernando

    2010-01-01

    Antiproliferative actions of calcitriol have been shown to occur in many cell types; however, little is known regarding the molecular basis of this process in breast carcinoma. Ether-a-go-go (Eag1) potassium channels promote oncogenesis and are implicated in breast cancer cell proliferation. Since calcitriol displays antineoplastic effects while Eag1 promotes tumorigenesis, and both factors antagonically regulate cell cycle progression, we investigated a possible regulatory effect of calcitriol upon Eag1 as a mean to uncover new molecular events involved in the antiproliferative activity of this hormone in human breast tumor-derived cells. RT real-time PCR and immunocytochemistry showed that calcitriol suppressed Eag1 expression by a vitamin D receptor (VDR)-dependent mechanism. This effect was accompanied by inhibition of cell proliferation, which was potentiated by astemizole, a nonspecific Eag1 inhibitor. Immunohistochemistry and Western blot demonstrated that Eag1 and VDR abundance was higher in invasive-ductal carcinoma than in fibroadenoma, and immunoreactivity of both proteins was located in ductal epithelial cells. Our results provide evidence of a novel mechanism involved in the antiproliferative effects of calcitriol and highlight VDR as a cancer therapeutic target for breast cancer treatment and prevention.

  7. Intratumor cholesteryl ester accumulation is associated with human breast cancer proliferation and aggressive potential: a molecular and clinicopathological study

    International Nuclear Information System (INIS)

    a Claret, 167 08025, Barcelona (Spain))" data-affiliation=" (Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Sant Antoni Ma Claret, 167 08025, Barcelona (Spain))" >Gonzalo-Calvo, David de; López-Vilaró, Laura; a Claret, 167 08025, Barcelona (Spain))" data-affiliation=" (Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Sant Antoni Ma Claret, 167 08025, Barcelona (Spain))" >Nasarre, Laura; Perez-Olabarria, Maitane; Vázquez, Tania; Escuin, Daniel; a Claret, 167 08025, Barcelona (Spain))" data-affiliation=" (Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Sant Antoni Ma Claret, 167 08025, Barcelona (Spain))" >Badimon, Lina; Barnadas, Agusti; Lerma, Enrique; a Claret, 167 08025, Barcelona (Spain))" data-affiliation=" (Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Sant Antoni Ma Claret, 167 08025, Barcelona (Spain))" >Llorente-Cortés, Vicenta

    2015-01-01

    The metabolic effect of intratumor cholesteryl ester (CE) in breast cancer remains poorly understood. The objective was to analyze the relationship between intratumor CE content and clinicopathological variables in human breast carcinomas. We classified 30 breast carcinoma samples into three subgroups: 10 luminal-A tumors (ER+/PR+/Her2-), 10 Her-2 tumors (ER-/PR-/Her2+), and 10 triple negative (TN) tumors (ER-/PR-/Her2-). We analyzed intratumor neutral CE, free cholesterol (FC) and triglyceride (TG) content by thin layer chromatography after lipid extraction. RNA and protein levels of lipid metabolism and invasion mediators were analyzed by real time PCR and Western blot analysis. Group-wise comparisons, linear regression and logistic regression models showed a close association between CE-rich tumors and higher histologic grade, Ki-67 and tumor necrosis. CE-rich tumors displayed higher mRNA and protein levels of low-density lipoprotein receptor (LDLR) and scavenger receptor class B member 1 (SCARB1). An increased expression of acetyl-Coenzyme A acetyltransferase 1 (ACAT1) in CE-rich tumors was also reported. Intratumor CE accumulation is intimately linked to proliferation and aggressive potential of breast cancer tumors. Our data support the link between intratumor CE content and poor clinical outcome and open the door to new antitumor interventions. The online version of this article (doi:10.1186/s12885-015-1469-5) contains supplementary material, which is available to authorized users

  8. Good performance of an immunoassay based method for nevirapine measurements in human breast milk

    DEFF Research Database (Denmark)

    Salado-Rasmussen, Kirsten; Persson Theilgaard, Zahra; Chiduo, Mercy

    2011-01-01

    , developed and validated for plasma use. In this study, the ARK NVP-test was evaluated for measurement of nevirapine concentrations in breast milk. High performance liquid chromatography (HPLC) is the method currently used to determine nevirapine in breast milk. This method, however, requires complicated...

  9. Immortalization protocols used in cell culture models of human breast morphogenesis

    DEFF Research Database (Denmark)

    Gudjonsson, T; Villadsen, R; Rønnov-Jessen, L

    2004-01-01

    of the tissue of origin. In recent years, we have sought to establish immortalized primary breast cells, which retain crucial characteristics of their original in situ tissue pattern. This review discusses various approaches to immortalization of breast-derived epithelial and stromal cells and the application...

  10. Putative Biomarkers and Targets of Estrogen Receptor Negative Human Breast Cancer

    Directory of Open Access Journals (Sweden)

    Stephen W. Byers

    2011-07-01

    Full Text Available Breast cancer is a progressive and potentially fatal disease that affects women of all ages. Like all progressive diseases, early and reliable diagnosis is the key for successful treatment and annihilation. Biomarkers serve as indicators of pathological, physiological, or pharmacological processes. Her2/neu, CA15.3, estrogen receptor (ER, progesterone receptor (PR, and cytokeratins are biomarkers that have been approved by the Food and Drug Administration for disease diagnosis, prognosis, and therapy selection. The structural and functional complexity of protein biomarkers and the heterogeneity of the breast cancer pathology present challenges to the scientific community. Here we review estrogen receptor-related putative breast cancer biomarkers, including those of putative breast cancer stem cells, a minor population of estrogen receptor negative tumor cells that retain the stem cell property of self renewal. We also review a few promising cytoskeleton targets for ER alpha negative breast cancer.

  11. Amplexicaule A exerts anti-tumor effects by inducing apoptosis in human breast cancer

    Science.gov (United States)

    Shu, Guangwen; Wan, Dingrong; He, Feng; Loaec, Morgann; Ding, Yali; Li, Jun; Dovat, Sinisa; Yang, Gaungzhong; Song, Chunhua

    2016-01-01

    Chemotherapy is the main treatment for patients with breast cancer metastases, but natural alternatives have been receiving attention for their potential as novel anti-tumor reagents. Amplexicaule A (APA) is a flavonoid glucoside isolated from rhizomes of Polygonum amplexicaule D. Don var. sinense Forb (PADF). We found that APA has anti-tumor effects in a breast cancer xenograft mouse model and induces apoptosis in breast cancer cell lines. APA increased levels of cleaved caspase-3,-8,-9 and PARP, which resulted from suppression of MCL-1 and BCL-2 expression in the cells. APA also inactivated the Akt/mTOR pathway in breast cancer cells. Thus, APA exerts a strong anti-tumor effect on breast cancer cells, most likely through induction of apoptosis. Our study is the first to identify this novel anti-tumor compound and provides a new strategy for isolation and separation of single compounds from herbs. PMID:26943775

  12. Gene expression profiling of histologically normal breast tissue in females with human epidermal growth factor receptor 2‑positive breast cancer.

    Science.gov (United States)

    Zubor, Pavol; Hatok, Jozef; Moricova, Petra; Kapustova, Ivana; Kajo, Karol; Mendelova, Andrea; Sivonova, Monika Kmetova; Danko, Jan

    2015-02-01

    Gene expression profile‑based taxonomy of breast cancer (BC) has been described as a significant breakthrough in comprehending the differences in the origin and behavior of cancer to allow individually tailored therapeutic approaches. In line with this, we hypothesized that the gene expression profile of histologically normal epithelium (HNEpi) could harbor certain genetic abnormalities predisposing breast tissue cells to develop human epidermal growth factor receptor 2 (HER2)‑positive BC. Thus, the aim of the present study was to assess gene expression in normal and BC tissue (BCTis) from patients with BC in order to establish its value as a potential diagnostic marker for cancer development. An array study evaluating a panel of 84 pathway‑ and disease‑specific genes in HER2‑positive BC and tumor‑adjacent HNEpi was performed using quantitative polymerase chain reaction in 12 patients using microdissected samples from frozen tissue. Common prognostic and predictive parameters of BC were assessed by immunohistochemistry and in situ hybridization. In the BCTis and HNEpi samples of 12 HER2‑positive subjects with BC, the expression of 2,016 genes was assessed. A total of 39.3% of genes were deregulated at a minimal two‑fold deregulation rate and 10.7% at a five‑fold deregulation rate in samples of HNEpi or BCTis. Significant differences in gene expression between BCTis and HNEpi samples were revealed for BCL2L2, CD44, CTSD, EGFR, ERBB2, ITGA6, NGFB, RPL27, SCBG2A1 and SCGB1D2 genes (Pbreast tissue revealed gene expression abnormalities that may represent potential markers of increased risk for HER2‑positive malignant transformation of breast tissue, and may be able to be employed as predictors of prognosis.

  13. In vitro response of the human breast cancer cell line MDAMB-231 and human peripheral blood mononuclear cells exposed to 60Co at single fraction

    International Nuclear Information System (INIS)

    Andrade, Lidia Maria; Campos, Tarcisio Passos Ribeiro de; Leite, M.F.; Goes, A.M.

    2005-01-01

    Radiotherapy using gamma rays is a common modality of breast cancer treatment. The aim of this research is to investigate the biological response of the human breast cancer cell line MDAMB-231 and human peripheral blood mononuclear cells (PBMC) exposed in vitro to 60 Co irradiation at a single fraction of 10 Gy, 25 Gy and 50 Gy doses at 136,4 cGy.min -1 rate. Cells were irradiated at room temperature by the Theratron 80 radiotherapy system. Biological response was evaluated through cellular viability using MTT assay and nucleus damages visualized by Propidium Iodide assay and electrophoresis agarose gel after gamma irradiation. Nucleus damages induced by 60 Co irradiation were compared to damage caused by cell exposure to 10% methanol. The 50 Gy dose of irradiation did not stimulate nucleus damages at the same level as that affected by 10% methanol induction in the MDAMB-231. Further studies are necessary to understand these mechanisms in the MDAMB-231 human breast carcinoma cell line.(author)

  14. In vitro response of the human breast cancer cell line MDAMB-231 and human peripheral blood mononuclear cells exposed to {sup 60}Co at single fraction

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Lidia Maria; Campos, Tarcisio Passos Ribeiro de [Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil). Dept. de Engenharia Nuclear]. E-mail: lidia.andrade@unifenas.br; Leite, M.F. [Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil). Dept. de Fisiologia e Biofisica; Goes, A.M. [Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil). Dept. de Bioquimica e Imunologia

    2005-10-15

    Radiotherapy using gamma rays is a common modality of breast cancer treatment. The aim of this research is to investigate the biological response of the human breast cancer cell line MDAMB-231 and human peripheral blood mononuclear cells (PBMC) exposed in vitro to {sup 60} Co irradiation at a single fraction of 10 Gy, 25 Gy and 50 Gy doses at 136,4 cGy.min{sup -1} rate. Cells were irradiated at room temperature by the Theratron 80 radiotherapy system. Biological response was evaluated through cellular viability using MTT assay and nucleus damages visualized by Propidium Iodide assay and electrophoresis agarose gel after gamma irradiation. Nucleus damages induced by {sup 60} Co irradiation were compared to damage caused by cell exposure to 10% methanol. The 50 Gy dose of irradiation did not stimulate nucleus damages at the same level as that affected by 10% methanol induction in the MDAMB-231. Further studies are necessary to understand these mechanisms in the MDAMB-231 human breast carcinoma cell line.(author)

  15. Potentiation of radiosensitivity by tetrandrine in human breast cancer cells and its mechanism

    International Nuclear Information System (INIS)

    Sun Xinchen; Zhen Yongsu; Shao Rongguang; Wang Junjie

    2003-01-01

    Objective: To investigate the potentiation of radiosensitivity and mechanism by tetrandrine (Tet) in human breast cancer p53-mutant MCF-7/ADR and p53-wt MCF-7 cells. Methods: Clonogenic assay, flow cytometry, Western blotting were preformed in this experiment. Results: The data of clonogenic assay showed that Tet markedly sensitized MCF-7/ADR cell to X-rays, and the sensitization enhancement ratio (SER) of Tet was 1.51. Flow cytometry assay showed that exposure of MCF-7/ADR cells to X-rays caused cells to arrest in G 2 phase, whereas Tet was able to lower the number of cells arrested in G 2 phase. However, in MCF-7 cells, the potentiation effect of Tet was lower, and its SER was 1.10. MCF-7 cells were induced to arrest in G 1 and G 2 phases by X-rays, and the number of cells arrested in G 2 phase abrogated by Tet was less than that in MCF-7/ADR cells. Furthermore, the results showed that the levels of Cyclin B1 and Cdc2 expression decreased after X-irradiation, and the mitotic index was lower too. Tet could reverse this decrease and induce X-ray-irradiated cells to enter mitosis. Conclusion: Tet is a potent G 2 checkpoint abrogator and markedly enhances the cytotoxicity of X irradiation in the p53-mutant cancer cells

  16. Phorbol ester induced phosphorylation of the estrogen receptor in intact MCF-7 human breast cancer cells

    International Nuclear Information System (INIS)

    Knabbe, C.; Lippman, M.E.; Greene, G.L.; Dickson, R.B.

    1986-01-01

    Recent studies with a variety of cellular receptors have shown that phorbol ester induced phosphorylation modulates ligand binding and function. In this study the authors present direct evidence that the estrogen receptor in MCF-7 human breast cancer cells is a phosphoprotein whose phosphorylation state can be enhanced specifically by phorbol-12-myristate-13-acetate (PMA). Cells were cultured to 6h in the presence of [ 32 P]-orthophosphate. Whole cell extracts were immunoprecipitated with a monoclonal antibody (D58) against the estrogen receptor and subjected to SDS-polyacrylamide electrophoresis. Autoradiography showed a specific band in the region of 60-62 kDa which was significantly increased in preparations from PMA treated cells. Phospho-amino acid analysis demonstrated specific phosphorylation of serine and threonine residues. Cholera toxin or forskolin did not change the phosphorylation state of this protein. In a parallel binding analysis PMA led to a rapid decrease of estrogen binding sites. The estrogen induction of both progesterone receptors and growth in semisolid medium was blocked by PMA, whereas the estrogen induction of the 8kDa protein corresponding to the ps2 gene product and of the 52 kDa protein was not affected. In conclusion, phorbol esters can induce phosphorylation of the estrogen receptor. This process may be associated with the inactivation of certain receptor functions

  17. Performance comparison of digital microRNA profiling technologies applied on human breast cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Erik Knutsen

    Full Text Available MicroRNA profiling represents an important first-step in deducting individual RNA-based regulatory function in a cell, tissue, or at a specific developmental stage. Currently there are several different platforms to choose from in order to make the initial miRNA profiles. In this study we investigate recently developed digital microRNA high-throughput technologies. Four different platforms were compared including next generation SOLiD ligation sequencing and Illumina HiSeq sequencing, hybridization-based NanoString nCounter, and miRCURY locked nucleic acid RT-qPCR. For all four technologies, full microRNA profiles were generated from human cell lines that represent noninvasive and invasive tumorigenic breast cancer. This study reports the correlation between platforms, as well as a more extensive analysis of the accuracy and sensitivity of data generated when using different platforms and important consideration when verifying results by the use of additional technologies. We found all the platforms to be highly capable for microRNA analysis. Furthermore, the two NGS platforms and RT-qPCR all have equally high sensitivity, and the fold change accuracy is independent of individual miRNA concentration for NGS and RT-qPCR. Based on these findings we propose new guidelines and considerations when performing microRNA profiling.

  18. Magnetic resonance imaging for monitoring the effects of thalidomide on experimental human breast cancers

    International Nuclear Information System (INIS)

    Cyran, Clemens C.; Sennino, Barbara; McDonald, Donald M.; Chaopathomkul, Bundit; Fu, Yanjun; Rogut, Victor S.; Shames, David M.; Wendland, Michael F.; Brasch, Robert C.

    2009-01-01

    Thalidomide, which inhibits angiogenesis in certain tumor types, reduced extravasation of a macromolec