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Sample records for adjacent normal breast

  1. Ki-67 Expression in Sclerosing Adenosis and Adjacent Normal Breast Terminal Ductal Lobular Units: A Nested Case-Control Study from the Mayo Benign Breast Disease Cohort

    PubMed Central

    Nassar, Aziza; Hoskin, Tanya L.; Stallings-Mann, Melody L.; Degnim, Amy C.; Radisky, Derek C.; Frost, Marlene H.; Vierkant, Robert A.; Hartmann, Lynn C.; Visscher, Daniel W.

    2015-01-01

    Purpose Sclerosing adenosis (SA) increases risk for invasive breast cancer (BC) 2.1 times relative to that in the general population. Here, we sought to evaluate whether the proliferation marker Ki-67 stratifies risk among women with SA. Methods A nested case-control sample of patients with SA was obtained from the Mayo Clinic Benign Breast Disease Cohort. Ki-67 expression was evaluated in SA lesions and in the adjacent normal terminal duct lobular units (TDLU) in women who did (cases, n =133) or did not (controls, n =239) develop BC. Ki67 was scored by intensity and number of positively stained cells per one high-power field (magnification, ×40) (40×HPF) for both SA and normal TDLU. Associations of Ki-67 expression with case-control status were assessed using conditional logistic regression. Results Higher Ki-67 expression was significantly associated with case-control status in both SA (P=.03) and normal background TDLU (P=.006). For the SA lesion, >2 average positively stained cells/40×HPF showed an adjusted odds ratio (OR) of 1.9 (95% CI, 1.1–3.4) compared to samples with an average of ≤2 positively stained cells. For background TDLU, lobules with >2 but ≤6 average positively stained cells showed an adjusted OR of 1.3 to 1.5, whereas those with an average of >6 positively stained cells had an OR of 2.4 (95% CI, 1.1–5.3) compared to those with an average of <2 positively stained cells. Conclusions Among women with SA, increased Ki-67 expression in either the SA lesion or the normal background TDLU carried an approximately 2-fold increased odds of subsequent BC as compared to lower Ki-67 expression. PMID:25863475

  2. Matrix metalloproteinase-1 expression in breast cancer and cancer-adjacent tissues by immunohistochemical staining

    PubMed Central

    XUAN, JIAJIA; ZHANG, YUNFENG; ZHANG, XIUJUN; HU, FEN

    2015-01-01

    Although matrix metalloproteinase-1 (MMP-1) has been considered a factor of crucial importance for breast cancer cells invasion and metastasis, the expression of MMP-1 in different breast cancer and cancer-adjacent tissues have not been fully examined. In the present study, immunohistochemical staining was used to detect the MMP-1 expression in non-specific invasive ductal carcinoma of the breast, cancer-adjacent normal breast tissue, lymph node metastatic non-specific invasive ductal carcinoma of the breast and normal lymph node tissue. The results showed that MMP-1 expression is different in the above tissues. MMP-1 had a positive expression in normal lymph node tissue and lymph node metastatic non-specific invasive ductal carcinoma. The MMP-1 negative expression rate was only 6.1% in non-specific invasive ductal carcinoma of the breast and 2.9% in cancer-adjacent normal breast tissue respectively. MMP-1 expression is higher in non-specific invasive ductal carcinoma and lymph node metastatic non-specific invasive ductal carcinoma compared to cancer-adjacent normal breast tissue and normal lymph node tissue. In conclusion, higher expression of MMP-1 in breast cancer may play a crucial role in promoting breast cancer metastasis. PMID:26137243

  3. Can Breast Tumors Affect the Oxidative Status of the Surrounding Environment? A Comparative Analysis among Cancerous Breast, Mammary Adjacent Tissue, and Plasma.

    PubMed

    Panis, C; Victorino, V J; Herrera, A C S A; Cecchini, A L; Simão, A N C; Tomita, L Y; Cecchini, R

    2015-01-01

    In this paper, we investigated the oxidative profile of breast tumors in comparison with their normal adjacent breast tissue. Our study indicates that breast tumors present enhanced oxidative/nitrosative stress, with concomitant augmented antioxidant capacity when compared to the adjacent normal breast. These data indicate that breast cancers may be responsible for the induction of a prooxidant environment in the mammary gland, in association with enhanced TNF-α and nitric oxide. PMID:26697139

  4. Can Breast Tumors Affect the Oxidative Status of the Surrounding Environment? A Comparative Analysis among Cancerous Breast, Mammary Adjacent Tissue, and Plasma.

    PubMed

    Panis, C; Victorino, V J; Herrera, A C S A; Cecchini, A L; Simão, A N C; Tomita, L Y; Cecchini, R

    2015-01-01

    In this paper, we investigated the oxidative profile of breast tumors in comparison with their normal adjacent breast tissue. Our study indicates that breast tumors present enhanced oxidative/nitrosative stress, with concomitant augmented antioxidant capacity when compared to the adjacent normal breast. These data indicate that breast cancers may be responsible for the induction of a prooxidant environment in the mammary gland, in association with enhanced TNF-α and nitric oxide.

  5. Genomic Changes in Normal Breast Tissue in Women at Normal Risk or at High Risk for Breast Cancer

    PubMed Central

    Danforth, David N.

    2016-01-01

    Sporadic breast cancer develops through the accumulation of molecular abnormalities in normal breast tissue, resulting from exposure to estrogens and other carcinogens beginning at adolescence and continuing throughout life. These molecular changes may take a variety of forms, including numerical and structural chromosomal abnormalities, epigenetic changes, and gene expression alterations. To characterize these abnormalities, a review of the literature has been conducted to define the molecular changes in each of the above major genomic categories in normal breast tissue considered to be either at normal risk or at high risk for sporadic breast cancer. This review indicates that normal risk breast tissues (such as reduction mammoplasty) contain evidence of early breast carcinogenesis including loss of heterozygosity, DNA methylation of tumor suppressor and other genes, and telomere shortening. In normal tissues at high risk for breast cancer (such as normal breast tissue adjacent to breast cancer or the contralateral breast), these changes persist, and are increased and accompanied by aneuploidy, increased genomic instability, a wide range of gene expression differences, development of large cancerized fields, and increased proliferation. These changes are consistent with early and long-standing exposure to carcinogens, especially estrogens. A model for the breast carcinogenic pathway in normal risk and high-risk breast tissues is proposed. These findings should clarify our understanding of breast carcinogenesis in normal breast tissue and promote development of improved methods for risk assessment and breast cancer prevention in women. PMID:27559297

  6. Genomic Changes in Normal Breast Tissue in Women at Normal Risk or at High Risk for Breast Cancer.

    PubMed

    Danforth, David N

    2016-01-01

    Sporadic breast cancer develops through the accumulation of molecular abnormalities in normal breast tissue, resulting from exposure to estrogens and other carcinogens beginning at adolescence and continuing throughout life. These molecular changes may take a variety of forms, including numerical and structural chromosomal abnormalities, epigenetic changes, and gene expression alterations. To characterize these abnormalities, a review of the literature has been conducted to define the molecular changes in each of the above major genomic categories in normal breast tissue considered to be either at normal risk or at high risk for sporadic breast cancer. This review indicates that normal risk breast tissues (such as reduction mammoplasty) contain evidence of early breast carcinogenesis including loss of heterozygosity, DNA methylation of tumor suppressor and other genes, and telomere shortening. In normal tissues at high risk for breast cancer (such as normal breast tissue adjacent to breast cancer or the contralateral breast), these changes persist, and are increased and accompanied by aneuploidy, increased genomic instability, a wide range of gene expression differences, development of large cancerized fields, and increased proliferation. These changes are consistent with early and long-standing exposure to carcinogens, especially estrogens. A model for the breast carcinogenic pathway in normal risk and high-risk breast tissues is proposed. These findings should clarify our understanding of breast carcinogenesis in normal breast tissue and promote development of improved methods for risk assessment and breast cancer prevention in women. PMID:27559297

  7. Divergent viral presentation among human tumors and adjacent normal tissues

    PubMed Central

    Cao, Song; Wendl, Michael C.; Wyczalkowski, Matthew A.; Wylie, Kristine; Ye, Kai; Jayasinghe, Reyka; Xie, Mingchao; Wu, Song; Niu, Beifang; Grubb, Robert; Johnson, Kimberly J.; Gay, Hiram; Chen, Ken; Rader, Janet S.; Dipersio, John F.; Chen, Feng; Ding, Li

    2016-01-01

    We applied a newly developed bioinformatics system called VirusScan to investigate the viral basis of 6,813 human tumors and 559 adjacent normal samples across 23 cancer types and identified 505 virus positive samples with distinctive, organ system- and cancer type-specific distributions. We found that herpes viruses (e.g., subtypes HHV4, HHV5, and HHV6) that are highly prevalent across cancers of the digestive tract showed significantly higher abundances in tumor versus adjacent normal samples, supporting their association with these cancers. We also found three HPV16-positive samples in brain lower grade glioma (LGG). Further, recurrent HBV integration at the KMT2B locus is present in three liver tumors, but absent in their matched adjacent normal samples, indicating that viral integration induced host driver genetic alterations are required on top of viral oncogene expression for initiation and progression of liver hepatocellular carcinoma. Notably, viral integrations were found in many genes, including novel recurrent HPV integrations at PTPN13 in cervical cancer. Finally, we observed a set of HHV4 and HBV variants strongly associated with ethnic groups, likely due to viral sequence evolution under environmental influences. These findings provide important new insights into viral roles of tumor initiation and progression and potential new therapeutic targets. PMID:27339696

  8. Jaw position uncertainty and adjacent fields in breast cancer radiotherapy.

    PubMed

    Hedin, Emma; Bäck, Anna; Chakarova, Roumiana

    2015-11-08

    Locoregional treatment of breast cancer involves adjacent, half blocked fields matched at isocenter. The objective of this work is to study the dosimetric effects of the uncertainties in jaw positioning for such a case, and how a treatment planning protocol including adjacent field overlap of 1 mm affects the dose distribution. A representative treatment plan, involving 6 and 15 photon beams, for a patient treated at our hospital is chosen. Monte Carlo method (EGSnrc/BEAMnrc) is used to simulate the treatment. Uncertainties in jaw positioning of ± 1 mm are addressed, which implies extremes in reality of 2 mm field gap/overlap when planning adjacent fields without overlap and 1 mm gap or 3 mm overlap for a planning protocol with 1 mm overlap. Dosimetric parameters for PTV, lung and body are analyzed. Treatment planning protocol with 1 mm overlap of the adjacent fields does not considerably counteract possible underdosage of the target in the case studied. PTV-V95% is for example reduced from 95% for perfectly aligned fields to 90% and 91% for 2 mm and 1 mm gap, respectively. However, the risk of overdosage in PTV and in healthy soft tissue is increased when following the protocol with 1 mm overlap. A 3 mm overlap compared to 2 mm overlap results in an increase in maximum dose to PTV, PTV-D2%, from 113% to 121%. V120% for 'Body-PTV' is also increased from 5 cm(3) to 14 cm(3). A treatment planning protocol with 1 mm overlap does not considerably improve the coverage of PTV in the case of erroneous jaw positions causing gap between fields, but increases the overdosage in PTV and doses to healthy tissue, in the case of overlapping fields, for the case investigated.

  9. Nuclear nano-morphology markers of histologically normal cells detect the "field effect" of breast cancer.

    PubMed

    Bista, Rajan K; Wang, Pin; Bhargava, Rohit; Uttam, Shikhar; Hartman, Douglas J; Brand, Randall E; Liu, Yang

    2012-08-01

    Accurate detection of breast malignancy from histologically normal cells ("field effect") has significant clinical implications in a broad base of breast cancer management, such as high-risk lesion management, personalized risk assessment, breast tumor recurrence, and tumor margin management. More accurate and clinically applicable tools to detect markers characteristic of breast cancer "field effect" that are able to guide the clinical management are urgently needed. We have recently developed a novel optical microscope, spatial-domain low-coherence quantitative phase microscopy, which extracts the nanoscale structural characteristics of cell nuclei (i.e., nuclear nano-morphology markers), using standard histology slides. In this proof-of-concept study, we present the use of these highly sensitive nuclear nano-morphology markers to identify breast malignancy from histologically normal cells. We investigated the nano-morphology markers from 154 patients with a broad spectrum of breast pathology entities, including normal breast tissue, non-proliferative benign lesions, proliferative lesions (without and with atypia), "malignant-adjacent" normal tissue, and invasive carcinoma. Our results show that the nuclear nano-morphology markers of "malignant-adjacent" normal tissue can detect the presence of invasive breast carcinoma with high accuracy and do not reflect normal aging. Further, we found that a progressive change in nuclear nano-morphology markers that parallel breast cancer risk, suggesting its potential use for risk stratification. These novel nano-morphology markers that detect breast cancerous changes from nanoscale structural characteristics of histologically normal cells could potentially benefit the diagnosis, risk assessment, prognosis, prevention, and treatment of breast cancer.

  10. Contralateral breast cancer adjacent to a fibroadenoma: report of a case.

    PubMed

    Iwamoto, Miki; Takei, Hiroyuki; Iida, Shinya; Yamashita, Kouji; Yanagihara, Keiko; Kurita, Tomoko; Tsuchiya, Shinichi; Kanazawa, Yoshikazu; Uchida, Eiji

    2014-01-01

    A 64-year-old woman noticed a lump of the right breast and consulted our outpatient clinic. She had undergone multiple excisional biopsies of fibroadenomas in both breasts and mastectomy for invasive ductal carcinoma (IDC) of the left breast. After completing 5 years of treatment with adjuvant tamoxifen, she had undergone screening with annual physical examinations and occasional computed tomography. She was declared recurrence-free 13 years after breast cancer surgery, although lumps were detected in the right breast, probably due to fibroadenomas. Mammography, ultrasonography, and magnetic resonance imaging revealed that the lump was irregularly shaped, 2 cm in diameter, and adjacent to a fibroadenoma with macrocalcification. Two axillary lymph nodes were enlarged and suggestive of metastasis. A core needle biopsy revealed IDC of the right breast. She underwent a right partial mastectomy with axillary lymph node dissection. The IDC was 2 cm in diameter, of nuclear grade 2, and adjacent to a 0.7-cm fibroadenoma with a macrocalcification. The margins of the IDC close to the fibroadenoma were clearly demarcated by the fibrous capsule of the fibroadenoma. Four axillary lymph nodes were positive for metastasis. In the present case the presence of fibroadenoma might have interfered with the early detection of the contralateral IDC. The history of multiple excisions of fibroadenomas and mastectomy for breast cancer suggests an increased risk of contralateral breast cancer for the patient's entire life; therefore, regular annual follow-up, such as physical examinations and mammography, is recommended. PMID:24998964

  11. p53 alteration in morphologically normal/benign breast tissue in patients with triple-negative high-grade breast carcinomas: breast p53 signature?

    PubMed

    Wang, Xi; Stolla, Moritz; Ring, Brian Z; Yang, Qi; Laughlin, Todd S; Rothberg, Paul G; Skinner, Kristin; Hicks, David G

    2016-09-01

    p53 alterations have been identified in approximately 23% of breast carcinomas, particularly in hormone receptor-negative high-grade carcinomas. It is considered to be an early event in breast carcinogenesis. Nevertheless, the putative precursor lesion of high-grade breast carcinoma remains elusive. Breast excision specimens from 93 triple-negative high-grade invasive ductal carcinomas, 48 estrogen receptor (ER)-positive/progesterone receptor-positive/Her2-negative non-high-grade invasive ductal carcinomas, and 50 mammoplasty breasts were selected. At least 2 tissue blocks with tumor and adjacent benign tissue were sectioned and subjected to immunohistochemistry staining for p53. TP53 gene sequencing was performed on select tumors. Further immunohistochemistry staining for ER and Ki-67 was performed on consecutive sections of tissue with p53-positive normal/benign cells. Of the 93 high-grade carcinomas, 51 (55%) were positive for p53 alteration, whereas only 3 (6.25%) of the 48 non-high-grade carcinomas were p53 altered. Focal p53 positivity in adjacent normal/benign breast tissue was identified in 19 cases, and 18 of them also had p53 alteration in their carcinomas. Only 1 case had focal p53 staining in normal/benign tissue, but the tumor was negative for p53 alteration. No p53 staining positivity was identified in the mammoplasty specimens. The p53-stained normal/benign cells were ER negative and did not show an increase in the Ki-67 labeling index. These findings indicate that the p53 staining positivity in normal/benign breast tissue is not a random event. It could be considered as the "p53 signature" in breast and serve as an indicator for future potential risk of p53-positive high-grade breast carcinoma.

  12. Expression of microRNA-370 in human breast cancer compare with normal samples

    PubMed Central

    Mollainezhad, Halimeh; Eskandari, Nahid; Pourazar, Abbasali; Salehi, Mansoor; Andalib, Alireza

    2016-01-01

    Background: Breast cancer is the second leading cause of deaths from cancer in the woman. MicroRNAs (miRNAs) are endogenous noncoding RNAs that are known critical player in carcinogenesis. The role of miR-370 in malignancies remains controversial because of its levels varying in different cancers according to its targets while the role of miR-370 in breast cancer has not been addressed so far. The aim of this study was to identify the expression pattern of miR-370 in human breast cancer tissue compared to adjacent healthy tissue. Materials and Methods: Twenty-two fresh frozen tissues (normal and malignant) from patients with breast cancer were examined for miR-370 by quantitative real-time polymerase chain reaction method at 2013. Results: We observed up-regulation (six-fold higher) of miR-370 in breast cancer tissue compared with normal adjacent tissue. Tumor samples in stage III, invasive ductal type, larger tumor size, human epidermal growth-factor receptor 2+, estrogen receptor/progesterone receptor−, P53 − status showed significantly increased expression in miR-370. Conclusion: Together, miR-370 may acts as an onco-miRNA, and it may have a novel role in breast cancer. Detection of miR-370 and its targets could be helpful as a diagnostic biomarker and therapeutic target. PMID:27563639

  13. Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Breast Carcinogenesis

    PubMed Central

    Margan, Madalin Marius; Jitariu, Andreea Adriana; Nica, Cristian; Raica, Marius

    2016-01-01

    Normal human breast tissue consists of epithelial and nonepithelial cells with different molecular profiles and differentiation grades. This molecular heterogeneity is known to yield abnormal clones that may contribute to the development of breast carcinomas. Stem cells that are found in developing and mature breast tissue are either positive or negative for cytokeratin 19 depending on their subtype. These cells are able to generate carcinogenesis along with mature cells. However, scientific data remains controversial regarding the monoclonal or polyclonal origin of breast carcinomas. The majority of breast carcinomas originate from epithelial cells that normally express BRCA1. The consecutive loss of the BRCA1 gene leads to various abnormalities in epithelial cells. Normal breast epithelial cells also express hypoxia inducible factor (HIF) 1α and HIF-2α that are associated with a high metastatic rate and a poor prognosis for malignant lesions. The nuclear expression of estrogen receptor (ER) and progesterone receptor (PR) in normal human breast tissue is maintained in malignant tissue as well. Several controversies regarding the ability of ER and PR status to predict breast cancer outcome remain. Both ER and PR act as modulators of cell activity in normal human breast tissue. Ki-67 positivity is strongly correlated with tumor grade although its specific role in applied therapy requires further studies. Human epidermal growth factor receptor 2 (HER2) oncoprotein is less expressed in normal human breast specimens but is highly expressed in certain malignant lesions of the breast. Unlike HER2, epidermal growth factor receptor expression is similar in both normal and malignant tissues. Molecular heterogeneity is not only found in breast carcinomas but also in normal breast tissue. Therefore, the molecular mapping of normal human breast tissue might represent a key research area to fully elucidate the mechanisms of breast carcinogenesis. PMID:27382385

  14. Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Breast Carcinogenesis.

    PubMed

    Margan, Madalin Marius; Jitariu, Andreea Adriana; Cimpean, Anca Maria; Nica, Cristian; Raica, Marius

    2016-06-01

    Normal human breast tissue consists of epithelial and nonepithelial cells with different molecular profiles and differentiation grades. This molecular heterogeneity is known to yield abnormal clones that may contribute to the development of breast carcinomas. Stem cells that are found in developing and mature breast tissue are either positive or negative for cytokeratin 19 depending on their subtype. These cells are able to generate carcinogenesis along with mature cells. However, scientific data remains controversial regarding the monoclonal or polyclonal origin of breast carcinomas. The majority of breast carcinomas originate from epithelial cells that normally express BRCA1. The consecutive loss of the BRCA1 gene leads to various abnormalities in epithelial cells. Normal breast epithelial cells also express hypoxia inducible factor (HIF) 1α and HIF-2α that are associated with a high metastatic rate and a poor prognosis for malignant lesions. The nuclear expression of estrogen receptor (ER) and progesterone receptor (PR) in normal human breast tissue is maintained in malignant tissue as well. Several controversies regarding the ability of ER and PR status to predict breast cancer outcome remain. Both ER and PR act as modulators of cell activity in normal human breast tissue. Ki-67 positivity is strongly correlated with tumor grade although its specific role in applied therapy requires further studies. Human epidermal growth factor receptor 2 (HER2) oncoprotein is less expressed in normal human breast specimens but is highly expressed in certain malignant lesions of the breast. Unlike HER2, epidermal growth factor receptor expression is similar in both normal and malignant tissues. Molecular heterogeneity is not only found in breast carcinomas but also in normal breast tissue. Therefore, the molecular mapping of normal human breast tissue might represent a key research area to fully elucidate the mechanisms of breast carcinogenesis. PMID:27382385

  15. Human breast cancer biopsies induce eosinophil recruitment and enhance adjacent cancer cell proliferation.

    PubMed

    Szalayova, Gabriela; Ogrodnik, Aleksandra; Spencer, Brianna; Wade, Jacqueline; Bunn, Janice; Ambaye, Abiy; James, Ted; Rincon, Mercedes

    2016-06-01

    Chronic inflammation is known to facilitate cancer progression and metastasis. Less is known about the effect of acute inflammation within the tumor microenvironment, resulting from standard invasive procedures. Recent studies in mouse models have shown that the acute inflammatory response triggered by a biopsy in mammary cancer increases the frequency of distal metastases. Although tumor biopsies are part of the standard clinical practice in breast cancer diagnosis, no studies have reported their effect on inflammatory response. The objective of this study is to (1) determine whether core needle biopsies in breast cancer patients trigger an inflammatory response, (2) characterize the type of inflammatory response present, and (3) evaluate the potential effect of any acute inflammatory response on residual tumor cells. The biopsy wound site was identified in the primary tumor resection tissue samples from breast cancer patients. The inflammatory response in areas adjacent (i.e., immediately around previous biopsy site) and distant to the wound biopsy was investigated by histology and immunohistochemistry analysis. Proliferation of tumor cells was also assayed. We demonstrate that diagnostic core needle biopsies trigger a selective recruitment of inflammatory cells at the site of the biopsy, and they persist for extended periods of time. While macrophages were part of the inflammatory response, an unexpected accumulation of eosinophils at the edge of the biopsy wound was also identified. Importantly, we show that biopsy causes an increase in the proliferation rate of tumor cells located in the area adjacent to the biopsy wound. Diagnostic core needle biopsies in breast cancer patients do induce a unique acute inflammatory response within the tumor microenvironment and have an effect on the surrounding tumor cells. Therefore, biopsy-induced inflammation could have an impact on residual tumor cell progression and/or metastasis in human breast cancer. These findings

  16. Differentially Expressed miRNAs in Tumor, Adjacent, and Normal Tissues of Lung Adenocarcinoma

    PubMed Central

    Tian, Fei; Li, Rui; Chen, Zhenzhu; Shen, Yanting; Lu, Jiafeng; Xie, Xueying; Ge, Qinyu

    2016-01-01

    Lung cancer is the leading cause of cancer deaths. Non-small-cell lung cancer (NSCLC) is the major type of lung cancer. The aim of this study was to characterize the expression profiles of miRNAs in adenocarcinoma (AC), one major subtype of NSCLC. In this study, the miRNAs were detected in normal, adjacent, and tumor tissues by next-generation sequencing. Then the expression levels of differential miRNAs were quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In the results, 259, 401, and 389 miRNAs were detected in tumor, adjacent, and normal tissues of pooled AC samples, respectively. In addition, for the first time we have found that miR-21-5p and miR-196a-5p were gradually upregulated from normal to adjacent to tumor tissues; miR-218-5p was gradually downregulated with 2-fold or greater change in AC tissues. These 3 miRNAs were validated by qRT-PCR. Lastly, we predicted target genes of these 3 miRNAs and enriched the potential functions and regulatory pathways. The aberrant miR-21-5p, miR-196a-5p, and miR-218-5p may become biomarkers for diagnosis and prognosis of lung adenocarcinoma. This research may be useful for lung adenocarcinoma diagnosis and the study of pathology in lung cancer. PMID:27247934

  17. Molecular heterogeneity in adjacent cells in triple-negative breast cancer

    PubMed Central

    Huebschman, Michael L; Lane, Nancy L; Liu, Huaying; Sarode, Venetia R; Devlin, Judith L; Frenkel, Eugene P

    2015-01-01

    Purpose This study interrogates the molecular status of individual cells in patients with triple-negative breast cancers and explores the molecular identification and characterization of these tumors to consider the exploitation of a potential-targeted therapeutic approach. Patients and methods Hyperspectral immunologic cell by cell analysis was applied to touch imprint smears obtained from fresh tumors of breast cancer patients. Results Cell by cell analysis confirms significant intratumoral molecular heterogeneity in cancer markers with differences from polymerase chain reaction marker reporting. The individual cell heterogeneity was recognized in adjacent cells examined with panels of ten molecular markers in each single cell and included some markers that are considered to express “stem-cell” character. In addition, heterogeneity did not relate either to the size or stage of the primary tumor or to the site from within the cancer. Conclusion There is a very significant molecular heterogeneity when “adjacent cells” are examined in triple-negative breast cancer, thereby making a successful targeted approach unlikely. In addition, it is not reasonable to consider that these changes will provide an answer to tumor dormancy. PMID:26316815

  18. Aluminum concentrations in central and peripheral areas of malignant breast lesions do not differ from those in normal breast tissues

    PubMed Central

    2013-01-01

    Background Aluminum is used in a wide range of applications and is a potential environmental hazard. The known genotoxic effects of aluminum might play a role in the development of breast cancer. However, the data currently available on the subject are not sufficient to establish a causal relationship between aluminum exposure and the augmented risk of developing breast cancer. To achieve maximum sensitivity and specificity in the determination of aluminum levels, we have developed a detection protocol using graphite furnace atomic absorption spectrometry (GFAAS). The objective of the present study was to compare the aluminum levels in the central and peripheral areas of breast carcinomas with those in the adjacent normal breast tissues, and to identify patient and/or tumor characteristics associated with these aluminum levels. Methods A total of 176 patients with breast cancer were included in the study. Samples from the central and peripheral areas of their tumors were obtained, as well as from the surrounding normal breast tissue. Aluminum quantification was performed using GFAAS. Results The average (mean ± SD) aluminum concentrations were as follows: central area, 1.88 ± 3.60 mg/kg; peripheral area, 2.10 ± 5.67 mg/kg; and normal area, 1.68 ± 11.1 mg/kg. Overall and two-by-two comparisons of the aluminum concentrations in these areas indicated no significant differences. We detected a positive relationship between aluminum levels in the peripheral areas of the tumors, age and menopausal status of the patients (P = .02). Conclusions Using a sensitive quantification technique we detected similar aluminum concentrations in the central and peripheral regions of breast tumors, and in normal tissues. In addition, we did not detect significant differences in aluminum concentrations as related to the location of the breast tumor within the breast, or to other relevant tumor features such as stage, size and steroid receptor status. The next

  19. Survivin expression in breast lobular carcinoma: correlations with normal breast tissue and clinicomorphological parameters.

    PubMed

    Adamkov, Marian; Výbohová, Desanka; Horáček, Jaroslav; Kovalská, Mária; Furjelová, Martina

    2013-06-01

    The antiapoptotic protein survivin is rarely expressed in normal adult differentiated tissues, but it is often detected in their malignant counterparts. Immunohistochemically, we evaluated survivin expression in 19 cases of normal breast tissue and 64 cases of lobular breast carcinoma. The intensity of staining, percentage of labeled cells and subcellular location of survivin were assessed. We analyzed the quantitative differences of survivin expression between normal breast tissue and carcinomas. We also correlated survivin expression pattern in carcinomas with clinicomorphological parameters such as age of patients, grade, stage and size of primary tumor, lymph node metastasis, vascular invasion as well as estrogen and progesterone status. Survivin was detected in 10/19 cases of normal breast tissue (52.6%) and in 55/64 cases of lobular breast carcinoma (86%). The statistical analysis confirmed significant correlations between the assessed parameters in normal breast and lobular carcinoma. Furthermore, the expression of estrogen correlated significantly with the subcellular localization and intensity of survivin in carcinoma. However, no significant correlation was shown with regard to other clinicomorphological parameters. Our results suggest that survivin may be a valuable diagnostic marker, as well as a new independent prognostic parameter, in lobular breast carcinoma. Finally, our data support the hypothesis that lobular and ductal breast carcinomas seem to be different clinicomorphological entities.

  20. Stem cells in normal mammary gland and breast cancer.

    PubMed

    Luo, Jie; Yin, Xin; Ma, Tao; Lu, Jun

    2010-04-01

    The mammary gland is a structurally dynamic organ that undergoes dramatic alterations with age, menstrual cycle, and reproductive status. Mammary gland stem cells, the minor cell population within the mature organ, are thought to have multiple functions in regulating mammary gland development, tissue maintenance, major growth, and structural remodeling. In addition, accumulative evidence suggests that breast cancers are initiated and maintained by a subpopulation of tumor cells with stem cell features (called cancer stem cells). A variety of methods have been developed to identify and characterize mammary stem cells, and several signal transduction pathways have been identified to be essential for the self-renewal and differentiation of mammary gland stem cells. Understanding the origin of breast cancer stem cells, their relationship to breast cancer development, and the differences between normal and cancer stem cells may lead to novel approaches to breast cancer diagnosis, prevention, and treatment.

  1. The normal breast epithelium of women with breast cancer displays an aberrant response to estradiol.

    PubMed

    Khan, S A; Sachdeva, A; Naim, S; Meguid, M M; Marx, W; Simon, H; Halverson, J D; Numann, P J

    1999-10-01

    Breast epithelial response to estradiol may play an important role in breast cancer etiology. We have examined the relationship between serum estradiol and progesterone levels and normal breast epithelial expression of estrogen receptor (ER) alpha, progesterone receptor (PgR), and epithelial proliferation (as reflected by the Ki-67 labeling index) in 121 women (50 newly diagnosed breast cancer cases and 71 benign breast disease controls). Simultaneous samples of grossly normal breast tissue and venous blood were obtained from women undergoing breast surgery. Serum estradiol and progesterone levels were measured by radioimmunoassay; breast epithelial ER, PgR, and Ki-67 expression was measured by immunohistochemistry. Linear regression, controlled for patient age and ductal and lobular composition of the tissue, showed that the breast epithelium of control women displayed an inverse correlation between serum estradiol and ER-alpha, which was not seen in case women (P for the difference in regression slopes = 0.001). PgR expression displayed a significant positive correlation with serum estradiol in cases, but not in controls. Epithelial proliferation had no relationship to either estradiol or progesterone in both cases and controls but showed an inverse relationship with ER in controls and a direct relationship in cases (P for the difference in regression slopes = 0.066). These results suggest a dysregulation of hormonal response in the normal breast epithelium of high-risk women, with lack of regulation of ER by estradiol, increased estrogen responsiveness as reflected by PgR expression, and a dissociation of ER expression and proliferative response.

  2. Distinctive Glycerophospholipid Profiles of Human Seminoma and Adjacent Normal Tissues by Desorption Electrospray Ionization Imaging Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Masterson, Timothy A.; Dill, Allison L.; Eberlin, Livia S.; Mattarozzi, Monica; Cheng, Liang; Beck, Stephen D. W.; Bianchi, Federica; Cooks, R. Graham

    2011-08-01

    Desorption electrospray ionization mass spectrometry (DESI-MS) has been successfully used to discriminate between normal and cancerous human tissue from different anatomical sites. On the basis of this, DESI-MS imaging was used to characterize human seminoma and adjacent normal tissue. Seminoma and adjacent normal paired human tissue sections (40 tissues) from 15 patients undergoing radical orchiectomy were flash frozen in liquid nitrogen and sectioned to 15 μm thickness and thaw mounted to glass slides. The entire sample was two-dimensionally analyzed by the charged solvent spray to form a molecular image of the biological tissue. DESI-MS images were compared with formalin-fixed, hematoxylin and eosin (H&E) stained slides of the same material. Increased signal intensity was detected for two seminolipids [seminolipid (16:0/16:0) and seminolipid (30:0)] in the normal tubule testis tissue; these compounds were undetectable in seminoma tissue, as well as from the surrounding fat, muscle, and blood vessels. A glycerophosphoinositol [PI(18:0/20:4)] was also found at increased intensity in the normal testes tubule tissue when compared with seminoma tissue. Ascorbic acid (i.e., vitamin C) was found at increased amounts in seminoma tissue when compared with normal tissue. DESI-MS analysis was successfully used to visualize the location of several types of molecules across human seminoma and normal tissues. Discrimination between seminoma and adjacent normal testes tubules was achieved on the basis of the spatial distributions and varying intensities of particular lipid species as well as ascorbic acid. The increased presence of ascorbic acid within seminoma compared with normal seminiferous tubules was previously unknown.

  3. Differentiating cancerous from normal breast tissue by redox imaging

    NASA Astrophysics Data System (ADS)

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

    2015-02-01

    Abnormal metabolism can be a hallmark of cancer occurring early before detectable histological changes and may serve as an early detection biomarker. The current gold standard to establish breast cancer (BC) diagnosis is histological examination of biopsy. Previously we have found that pre-cancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. Our technique of quantitatively measuring the mitochondrial redox state has the potential to be implemented as an early detection tool for cancer and may provide prognostic value. We therefore in this present study, investigated the feasibility of quantifying the redox state of tumor samples from 16 BC patients. Tumor tissue aliquots were collected from both normal and cancerous tissue from the affected cancer-bearing breasts of 16 female patients (5 TNBC, 9 ER+, 2 ER+/Her2+) shortly after surgical resection. All specimens were snap-frozen with liquid nitrogen on site and scanned later with the Chance redox scanner, i.e., the 3D cryogenic NADH/oxidized flavoprotein (Fp) fluorescence imager. Our preliminary results showed that both NADH and Fp (including FAD, i.e., flavin adenine dinucleotide) signals in the cancerous tissues roughly tripled to quadrupled those in the normal tissues (p<0.05) and the redox ratio Fp/(NADH+Fp) was about 27% higher in the cancerous tissues than in the normal ones (p<0.05). Our findings suggest that the redox state could differentiate between cancer and non-cancer breast tissues in human patients and this novel redox scanning procedure may assist in tissue diagnosis in freshly procured biopsy samples prior to tissue fixation. We are in the process of evaluating the prognostic value of the redox imaging indices for BC.

  4. Analysis of CUL-5 expression in breast epithelial cells, breast cancer cell lines, normal tissues and tumor tissues

    PubMed Central

    Fay, Michael J; Longo, Kenneth A; Karathanasis, George A; Shope, David M; Mandernach, Craig J; Leong, Jason R; Hicks, Alfred; Pherson, Kenneth; Husain, Amyna

    2003-01-01

    Background The chromosomal location of CUL-5 (11q 22-23) is associated with LOH in breast cancer, suggesting that CUL-5 may be a tumor suppressor. The purpose of this research was to determine if there is differential expression of CUL-5 in breast epithelial cells versus breast cancer cell lines, and normal human tissues versus human tumors. The expression of CUL-5 in breast epithelial cells (HMEC, MCF-10A), and breast cancer cells (MCF-7, MDA-MB-231) was examined using RT-PCR, Northern blot analysis, and Western blot analysis. The expression of mRNA for other CUL family members (CUL-1, -2, -3, -4A, and -4B) in these cells was evaluated by RT-PCR. A normal human tissue expression array and a cancer profiling array were used to examine CUL-5 expression in normal human tissues and matched normal tissues versus tumor tissues, respectively. Results CUL-5 is expressed at the mRNA and protein levels by breast epithelial cells (HMEC, MCF-10A) and breast cancer cells (MCF-7, MDA-MB-231). These cells also express mRNA for other CUL family members. The normal human tissue expression array revealed that CUL-5 is widely expressed. The cancer profiling array revealed that 82% (41/50) of the breast cancers demonstrated a decrease in CUL-5 expression versus the matched normal tissue. For the 50 cases of matched breast tissue there was a statistically significant ~2.2 fold decreased expression of CUL-5 in tumor tissue versus normal tissue (P < 0.0001). Conclusions The data demonstrate no apparent decrease in CUL-5 expression in the breast cancer cell lines (MCF-7, MDA-MB-231) versus the breast epithelial cells (HMEC, MCF-10A). The decrease in CUL-5 expression in breast tumor tissue versus matched normal tissue supports the hypothesis that decreased expression of CUL-5 may play a role in breast tumorigenesis. PMID:14641918

  5. Insulin-like growth factor receptor-1 (IGF-1R) expression in normal breast, proliferative breast lesions, and breast carcinoma.

    PubMed

    Bhargava, Rohit; Beriwal, Sushil; McManus, Kim; Dabbs, David J

    2011-05-01

    Insulin-like growth factor receptor 1 (IGF-1R) is a receptor protein tyrosine kinase that is activated by ligand (IGF-1) binding and promotes mitogenic, metastatic, and antiapoptotic phenotypes of breast cancer. There is a dearth of studies analyzing IGF-1R expression by immunohistochemistry in breast carcinoma. This biomarker analysis will be important for pharmacologic interventions that target the IGF system. IGF-1R expression pattern was first analyzed in normal breast tissue and a variety of breast lesions (71 diagnoses from 35 patients), followed by analysis in 191 consecutive invasive breast carcinomas. Furthermore, 86 carcinomas treated with neoadjuvant chemotherapy were also analyzed. The carcinomas were classified using immunohistochemical surrogate (to molecular classes) markers-estrogen receptors (ER), progesterone receptors, and human epidermal growth factor receptor 2. IGF-1R is expressed at moderate level in normal breast tissue which was considered as normal expression. Overexpression and lower expression were defined as higher than normal or lower than normal expression, respectively. Among the benign and noninvasive breast lesions, IGF-1R expression was slightly increased in lesions that are hormonally driven (such as atypical ductal hyperplasia and columnar cells changes) whereas it was significantly reduced in ER-negative lesions (such as apocrine metaplasia). Similarly, in 191 consecutive breast carcinomas, IGF-1R overexpression was predominantly seen in ER-positive+ tumors. The tumor group that consistently showed reduced expression was the ERBB2 group (ER negative/progesterone receptors negative/human epidermal growth factor receptor 2 positive). The expression was somewhat heterogeneous in the triple-negative group. IGF-1R expression was not predictive of pathologic complete response or tumor volume reduction in ER-negative tumors, but reduced IGF-1R was associated with pathologic complete response and significant tumor volume reduction in

  6. Proteomic profiling of 13 paired ductal infiltrating breast carcinomas and non-tumoral adjacent counterparts.

    PubMed

    Pucci-Minafra, Ida; Cancemi, Patrizia; Marabeti, Maria Rita; Albanese, Nadia Ninfa; Di Cara, Gianluca; Taormina, Pietra; Marrazzo, Antonio

    2007-01-01

    According to recent statistics, breast cancer remains one of the leading causes of death among women in Western countries. Breast cancer is a complex and heterogeneous disease, presently classified into several subtypes according to their cellular origin. Among breast cancer histotypes, infiltrating ductal carcinoma represents the most common and potentially aggressive form. Despite the current progress achieved in early cancer detection and treatment, including the new generation of molecular therapies, there is still need for identification of multiparametric biomarkers capable of discriminating between cancer subtypes and predicting cancer progression for personalized therapies. One established step in this direction is the proteomic strategy, expected to provide enough information on breast cancer profiling. To this aim, in the present study we analyzed 13 breast cancer tissues and their matched non-tumoral tissues by 2-DE. Collectively, we identified 51 protein spots, corresponding to 34 differentially expressed proteins, which may represent promising candidate biomarkers for molecular-based diagnosis of breast cancer and for pattern discovery. The relevance of these proteins as factors contributing to breast carcinogenesis is discussed. PMID:21136615

  7. Study of the response of osteogenic sarcoma and adjacent normal tissues to radiation. [/sup 60/Co

    SciTech Connect

    Gaitan-Yanguas, M.

    1981-05-01

    An analysis is made of the surgical specimens of 18 patients with hystologically-proven osteosarcoma who were treated with radiation as the first treatment, and submitted 6 months later to amputation (2 patients had only a second biopsy). Plotting of dose and treatment time against persistence or sterilization of the tumor shows that there is an intermediate zone that extends from 3200 to 5000 rad in 10 days to 8000 to 10,000 rad in 60 to 70 days, inside which the tumor may or may not be destroyed. All cases located above this zone were sterilized; and all those under it showed persistence of viable tumor cells. A similar correlation is made in 47 irradiated patients of the secondary reactions of normal skin and soft tissues surrounding the tumor. An intermediate zone also exists above which all reactions were severe, in some cases reaching necrosis; below this zone, all reactions were mild. When treatment time was longer than 45 days, reactions were only moderate.

  8. Simulation of Dose to Surrounding Normal Structures in Tangential Breast Radiotherapy Due to Setup Error

    SciTech Connect

    Prabhakar, Ramachandran Rath, Goura K.; Julka, Pramod K.; Ganesh, Tharmar; Haresh, K.P.; Joshi, Rakesh C.; Senthamizhchelvan, S.; Thulkar, Sanjay; Pant, G.S.

    2008-04-01

    Setup error plays a significant role in the final treatment outcome in radiotherapy. The effect of setup error on the planning target volume (PTV) and surrounding critical structures has been studied and the maximum allowed tolerance in setup error with minimal complications to the surrounding critical structure and acceptable tumor control probability is determined. Twelve patients were selected for this study after breast conservation surgery, wherein 8 patients were right-sided and 4 were left-sided breast. Tangential fields were placed on the 3-dimensional-computed tomography (3D-CT) dataset by isocentric technique and the dose to the PTV, ipsilateral lung (IL), contralateral lung (CLL), contralateral breast (CLB), heart, and liver were then computed from dose-volume histograms (DVHs). The planning isocenter was shifted for 3 and 10 mm in all 3 directions (X, Y, Z) to simulate the setup error encountered during treatment. Dosimetric studies were performed for each patient for PTV according to ICRU 50 guidelines: mean doses to PTV, IL, CLL, heart, CLB, liver, and percentage of lung volume that received a dose of 20 Gy or more (V20); percentage of heart volume that received a dose of 30 Gy or more (V30); and volume of liver that received a dose of 50 Gy or more (V50) were calculated for all of the above-mentioned isocenter shifts and compared to the results with zero isocenter shift. Simulation of different isocenter shifts in all 3 directions showed that the isocentric shifts along the posterior direction had a very significant effect on the dose to the heart, IL, CLL, and CLB, which was followed by the lateral direction. The setup error in isocenter should be strictly kept below 3 mm. The study shows that isocenter verification in the case of tangential fields should be performed to reduce future complications to adjacent normal tissues.

  9. Simulation of dose to surrounding normal structures in tangential breast radiotherapy due to setup error.

    PubMed

    Prabhakar, Ramachandran; Rath, Goura K; Julka, Pramod K; Ganesh, Tharmar; Haresh, K P; Joshi, Rakesh C; Senthamizhchelvan, S; Thulkar, Sanjay; Pant, G S

    2008-01-01

    Setup error plays a significant role in the final treatment outcome in radiotherapy. The effect of setup error on the planning target volume (PTV) and surrounding critical structures has been studied and the maximum allowed tolerance in setup error with minimal complications to the surrounding critical structure and acceptable tumor control probability is determined. Twelve patients were selected for this study after breast conservation surgery, wherein 8 patients were right-sided and 4 were left-sided breast. Tangential fields were placed on the 3-dimensional-computed tomography (3D-CT) dataset by isocentric technique and the dose to the PTV, ipsilateral lung (IL), contralateral lung (CLL), contralateral breast (CLB), heart, and liver were then computed from dose-volume histograms (DVHs). The planning isocenter was shifted for 3 and 10 mm in all 3 directions (X, Y, Z) to simulate the setup error encountered during treatment. Dosimetric studies were performed for each patient for PTV according to ICRU 50 guidelines: mean doses to PTV, IL, CLL, heart, CLB, liver, and percentage of lung volume that received a dose of 20 Gy or more (V20); percentage of heart volume that received a dose of 30 Gy or more (V30); and volume of liver that received a dose of 50 Gy or more (V50) were calculated for all of the above-mentioned isocenter shifts and compared to the results with zero isocenter shift. Simulation of different isocenter shifts in all 3 directions showed that the isocentric shifts along the posterior direction had a very significant effect on the dose to the heart, IL, CLL, and CLB, which was followed by the lateral direction. The setup error in isocenter should be strictly kept below 3 mm. The study shows that isocenter verification in the case of tangential fields should be performed to reduce future complications to adjacent normal tissues. PMID:18262128

  10. Differential expression of the Na+/I− symporter protein in thyroid cancer and adjacent normal and nodular goiter tissues

    PubMed Central

    WANG, SHASHA; LIANG, JUN; LIN, YANSONG; YAO, RUYONG

    2013-01-01

    The ability of differentiated thyroid cancer and adjacent thyroid cells to concentrate iodine is dependent on their expression of a functional NA+/I− symporter (NIS). Thyroid cancer is insensitive to 131I treatment if the thyroid cells lack the ability to concentrate iodide. Thus, in this study, we aimed to determine whether the NIS protein was differentially expressed in thyroid cancer and various surrounding tissues. We recruited 114 cases of papillary thyroid carcinoma (PTC) and divided them into two groups: 60 patients of 9 males and 51 females with a mean age of 49.55 years who had PTC with surrounding nodular goiter tissue (simplified as GNG), and 54 patients of 8 males and 46 females with a mean age of 45.78 years who had PTC with surrounding normal tissue (Gnormal) after total or near total thyroidectomy. Formalin-fixed and paraffin-embedded tissue sections were prepared for immunohistochemical staining of the NIS protein and semi-quantitative analysis. The NIS protein was expressed in the basolateral membrane of the normal epithelium, while PTC and nodular goiter cells expressed NIS in the cytoplasm and basolateral membrane. The expression levels of the NIS protein were higher in the adjacent normal tissues compared with those of the surrounding nodular goiter tissues (P=0.002) and expression levels of the NIS protein were higher in PTC tissues compared with the surrounding nodular goiter tissues (P=0.008). The data from this study indicate that cancer-surrounding tissues may play a significant role in mediating the sensitivity of PTC patients to radioactive iodine treatment. PMID:23255951

  11. GPER mediates estrogen-induced signaling and proliferations in human breast epithelial cells, and normal and malignant breast

    PubMed Central

    Scaling, Allison L.

    2014-01-01

    17β-estradiol (estrogen), through receptor binding and activation, is required for mammary gland development. Estrogen stimulates epithelial proliferation in the mammary gland, promoting ductal elongation and morphogenesis. In addition to a developmental role, estrogen promotes proliferation in tumorigenic settings, particularly breast cancer. The proliferative effects of estrogen in the normal breast and breast tumors are attributed to estrogen receptor α. Although in vitro studies have demonstrated that the G protein-coupled estrogen receptor (GPER, previously called GPR30) can modulate proliferation in breast cancer cells both positively and negatively depending on cellular context, its role in proliferation in the intact normal or malignant breast remains unclear. Estrogen-induced GPER-dependent proliferation was assessed in the immortalized non-tumorigenic human breast epithelial cell line, MCF10A, and an ex vivo organ culture model employing human breast tissue from reduction mammoplasty or tumor resections. Stimulation by estrogen and the GPER-selective agonist G-1 increased the mitotic index in MCF10A cells and proportion of cells in the cell cycle in human breast and breast cancer explants, suggesting increased proliferation. Inhibition of candidate signaling pathways that may link GPER activation to proliferation revealed a dependence on Src, epidermal growth factor receptor transactivation by heparin-bound EGF and subsequent ERK phosphorylation. Proliferation was not dependent on matrix metalloproteinase cleavage of membrane bound pro-HB-EGF. The contribution of GPER to estrogen-induced proliferation in MCF10A cells and breast tissue was confirmed by the ability of GPER-selective antagonist G36 to abrogate estrogen- and G-1-induced proliferation, and the ability of siRNA knockdown of GPER to reduce estrogen- and G-1-induced proliferation in MCF10A cells. This is the first study to demonstrate GPER-dependent proliferation in primary normal and malignant

  12. GPER mediates estrogen-induced signaling and proliferation in human breast epithelial cells and normal and malignant breast.

    PubMed

    Scaling, Allison L; Prossnitz, Eric R; Hathaway, Helen J

    2014-06-01

    17β-Estradiol (estrogen), through receptor binding and activation, is required for mammary gland development. Estrogen stimulates epithelial proliferation in the mammary gland, promoting ductal elongation and morphogenesis. In addition to a developmental role, estrogen promotes proliferation in tumorigenic settings, particularly breast cancer. The proliferative effects of estrogen in the normal breast and breast tumors are attributed to estrogen receptor α. Although in vitro studies have demonstrated that the G protein-coupled estrogen receptor (GPER, previously called GPR30) can modulate proliferation in breast cancer cells both positively and negatively depending on cellular context, its role in proliferation in the intact normal or malignant breast remains unclear. Estrogen-induced GPER-dependent proliferation was assessed in the immortalized nontumorigenic human breast epithelial cell line, MCF10A, and an ex vivo organ culture model employing human breast tissue from reduction mammoplasty or tumor resections. Stimulation by estrogen and the GPER-selective agonist G-1 increased the mitotic index in MCF10A cells and proportion of cells in the cell cycle in human breast and breast cancer explants, suggesting increased proliferation. Inhibition of candidate signaling pathways that may link GPER activation to proliferation revealed a dependence on Src, epidermal growth factor receptor transactivation by heparin-bound EGF and subsequent ERK phosphorylation. Proliferation was not dependent on matrix metalloproteinase cleavage of membrane-bound pro-HB-EGF. The contribution of GPER to estrogen-induced proliferation in MCF10A cells and breast tissue was confirmed by the ability of GPER-selective antagonist G36 to abrogate estrogen- and G-1-induced proliferation, and the ability of siRNA knockdown of GPER to reduce estrogen- and G-1-induced proliferation in MCF10A cells. This is the first study to demonstrate GPER-dependent proliferation in primary normal and malignant

  13. The normal breast microenvironment of premenopausal women differentially influences the behavior of breast cancer cells in vitro and in vivo

    PubMed Central

    2010-01-01

    Background Breast cancer studies frequently focus on the role of the tumor microenvironment in the promotion of cancer; however, the influence of the normal breast microenvironment on cancer cells remains relatively unknown. To investigate the role of the normal breast microenvironment on breast cancer cell tumorigenicity, we examined whether extracellular matrix molecules (ECM) derived from premenopausal African-American (AA) or Caucasian-American (CAU) breast tissue would affect the tumorigenicity of cancer cells in vitro and in vivo. We chose these two populations because of the well documented predisposition of AA women to develop aggressive, highly metastatic breast cancer compared to CAU women. Methods The effects of primary breast fibroblasts on tumorigenicity were analyzed via real-time PCR arrays and mouse xenograft models. Whole breast ECM was isolated, analyzed via zymography, and its effects on breast cancer cell aggressiveness were tested in vitro via soft agar and invasion assays, and in vivo via xenograft models. Breast ECM and hormone metabolites were analyzed via mass spectrometry. Results Mouse mammary glands humanized with premenopausal CAU fibroblasts and injected with primary breast cancer cells developed significantly larger tumors compared to AA humanized glands. Examination of 164 ECM molecules and cytokines from CAU-derived fibroblasts demonstrated a differentially regulated set of ECM proteins and increased cytokine expression. Whole breast ECM was isolated; invasion and soft agar assays demonstrated that estrogen receptor (ER)-, progesterone receptor (PR)/PR- cells were significantly more aggressive when in contact with AA ECM, as were ER+/PR+ cells with CAU ECM. Using zymography, protease activity was comparatively upregulated in CAU ECM. In xenograft models, CAU ECM significantly increased the tumorigenicity of ER+/PR+ cells and enhanced metastases. Mass spectrometry analysis of ECM proteins showed that only 1,759 of approximately 8

  14. Differentiating fibroadenoma and ductal carcinoma in situ from normal breast tissue by multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Nie, Yuting; Wu, Yan; Lian, Yuane; Fu, Fangmeng; Wang, Chuan; Chen, Jianxin

    2014-09-01

    Fibroadenoma (FA) is the most common benign tumor of the female breast and several studies have reported that women with it have increased risk of breast cancer. While the ductal carcinoma in situ (DCIS) is a very early form of breast cancer. Thus, early detections of FA and DCIS are critical for improving breast tumor outcome and survival. In this paper, we use multiphoton microscopy (MPM) to obtain the high-contrast images of fresh, unfixed, unstained human breast specimens (normal breast tissue, FA and DCIS). Our results show that MPM has the ability to identify the characteristics of FA and DCIS including changes of duct architecture and collagen morphology. These results are consistent with the histological results. With the advancement of MPM, the technique has potential ability to serve as a real-time noninvasive imaging tool for early detection of breast tumor.

  15. Use of high-throughput protein array for profiling of differentially expressed proteins in normal and malignant breast tissue.

    PubMed

    Hudelist, Gernot; Pacher-Zavisin, Margit; Singer, Christian F; Holper, Tina; Kubista, Ernst; Schreiber, Martin; Manavi, Mahmood; Bilban, Martin; Czerwenka, Klaus

    2004-08-01

    cDNA arrays provide a powerful tool to identify gene expression pattern that are potentially associated with tumor invasion and metastasis. However, genes work at the protein level and, since the transcriptional activity of a gene does not necessarily reflect cellular protein expression, the identification and quantification of proteins is essential for the understanding of molecular events leading to malignant transformation. We have therefore employed a high-throughput protein microarray system which contains 378 well-characterized monoclonal antibodies in order to compare the gene expression pattern of malignant and adjacent normal breast tissue in a patient with primary breast cancer. Using this technique, we have identified a number of proteins that show increased expression levels in malignant breast tissues such as casein kinase Ie, p53, annexin XI, CDC25C, eIF-4E and MAP kinase 7. The expression of other proteins, such as the multifunctional regulator 14-3-3e was found to be decreased in malignant breast tissue, whereas the majority of proteins remained unchanged when compared to the corresponding non-malignant samples. The protein expression pattern was confirmed by immunohistochemistry, in which antibodies against 8 representative proteins known to be involved in carcinogenesis were employed in paraffin-embedded normal and malignant tissue sections deriving from the same patient. In each case, the results obtained by IHC matched the data obtained by antibody microarray system. Taken together, we have described for the first time a tumor cell specificity protein expression pattern by use of a novel commercially available antibody microarray system. We have thus demonstrated the feasibility of high-throughput protein arrays in the proteomic analysis of human breast tissue. We hypothesize that the use of protein arrays will not only increase our understanding of the molecular events, but could prove useful in evaluating prognosis and in determining optimal

  16. The 8th international symposium on the breast: Using next-generation science to understand the normal breast and the development of breast cancer- conference report.

    PubMed

    Gomberawalla, Ameer; Love, Susan

    2015-12-01

    Dr. Susan Love Research Foundation is committed to performing and advancing research that will lead to the discovery of what causes cancer to develop in the human breast. As part of this effort, the Foundation hosted the 8th International Symposium on the Breast in Santa Monica, Calif., Feb. 19 to Feb. 21, 2015. More than 120 forward-thinking clinical researchers, epidemiologists, pathologists, basic scientists, translational investigators, and breast cancer advocates from six countries attended this year's conference, "Using Next Generation Science to Understand the Normal Breast and the Development of Cancer." The highlights from this year's symposium are summarized in this report.

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

    PubMed

    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.

  18. Lysyl oxidase-like 2 promotes migration in noninvasive breast cancer cells but not in normal breast epithelial cells.

    PubMed

    Hollosi, Peter; Yakushiji, Jana K; Fong, Keith S K; Csiszar, Katalin; Fong, Sheri F T

    2009-07-15

    A growing number of studies indicate the importance of the lysyl oxidase family in the promotion of epithelial neoplasms towards their more aggressive forms. However, the role of individual family members in carcinoma progression has yet to be ascertained. In this study, we analyzed LOXL2 expression in malignantly transformed MCF-7 and normal MCF-10A mammary epithelial cell line clones stably transduced with LOXL2 in vitro, and in normal and cancerous breast tissue samples in vivo. We found LOXL2 to be catalytically active in both MCF-7 and MCF-10 clones. LOXL2 overexpression promoted a more mesenchymal morphology in both cell types, but LOXL2-induced increase in migratory ability could only be established in MCF-7 clones. We demonstrated altered localization of the LOXL2 protein in breast cancer tissue compared to normal mammary tissue, and altered localization and processing of LOXL2 protein in breast cancer cell lines compared to normal cell lines, which may allow LOXL2 to interact with different intra and extracellular components during tumor progression. Results support the role of LOXL2 in selectively promoting a metastatic phenotype in breast tumor cells. Additional data suggest epigenetic molecular mechanisms in tumor specific regulation of LOXL2 expression that could be explored as a molecular target in the prevention of breast cancer progression.

  19. Trace elemental correlation study in malignant and normal breast tissue by PIXE technique

    NASA Astrophysics Data System (ADS)

    Raju, G. J. Naga; Sarita, P.; Kumar, M. Ravi; Murty, G. A. V. Ramana; Reddy, B. Seetharami; Lakshminarayana, S.; Vijayan, V.; Lakshmi, P. V. B. Rama; Gavarasana, Satyanarayana; Reddy, S. Bhuloka

    2006-06-01

    Particle induced X-ray emission technique was used to study the variations in trace elemental concentrations between normal and malignant human breast tissue specimens and to understand the effects of altered homeostasis of these elements in the etiology of breast cancer. A 3 MeV proton beam was used to excite the biological samples of normal and malignant breast tissues. The elements Cl, K, Ca, Ti, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Br, Rb and Sr were identified and their relative concentrations were estimated. Almost all the elements were found to be elevated (p < 0.05, Wilcoxon signed-ranks test) in the cancerous tissues when compared with normal tissues. The excess levels of trace elements observed in the cancerous breast tissues could either be a cause or a consequence of breast cancer. Regarding their role in the initiation or promotion of breast cancer, one possible interpretation is that the elevated levels of Cu, Fe and Cr could have led to the formation of free radicals or other reactive oxygen species (ROS) that adversely affect DNA thereby causing breast cancer, which is mainly attributed to genetic abnormalities. Moreover, since Cu and Fe are required for angiogenesis, elevated concentrations of these elements are likely to promote breast cancer by increasing the blood supply for tumor growth. On the other hand elevated concentrations of elements in breast cancer tissues might also be a consequence of the cancer. This can be understood in terms of the biochemical and histological differences between normal and cancerous breast tissues. Tumors, characterized by unregulated multiplication of cells, need an ever-increasing supply of essential nutrients including trace elements. This probably results in an increased vascularity of malignant tissues, which in turn leads to enhancement of elemental concentrations in tumors.

  20. Identification of the boundary between normal breast tissue and invasive ductal carcinoma during breast-conserving surgery using multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Deng, Tongxin; Nie, Yuting; Lian, Yuane; Wu, Yan; Fu, Fangmeng; Wang, Chuan; Zhuo, Shuangmu; Chen, Jianxin

    2014-11-01

    Breast-conserving surgery has become an important way of surgical treatment for breast cancer worldwide nowadays. Multiphoton microscopy (MPM) has the ability to noninvasively visualize tissue architectures at the cellular level using intrinsic fluorescent molecules in biological tissues without the need for fluorescent dye. In this study, MPM is used to image the microstructures of terminal duct lobular unit (TDLU), invasive ductal carcinoma and the boundary region between normal and cancerous breast tissues. Our study demonstrates that MPM has the ability to not only reveal the morphological changes of the cuboidal epithelium, basement membrane and interlobular stroma but also identify the boundary between normal breast tissue and invasive ductal carcinoma, which correspond well to the Hematoxylin and Eosin (H and E) images. Predictably, MPM can monitor surgical margins in real time and provide considerable accuracy for resection of breast cancerous tissues intraoperatively. With the development of miniature, real-time MPM imaging technology, MPM should have great application prospects during breast-conserving surgery.

  1. Taxonomy of breast cancer based on normal cell phenotype predicts outcome

    PubMed Central

    Santagata, Sandro; Thakkar, Ankita; Ergonul, Ayse; Wang, Bin; Woo, Terri; Hu, Rong; Harrell, J. Chuck; McNamara, George; Schwede, Matthew; Culhane, Aedin C.; Kindelberger, David; Rodig, Scott; Richardson, Andrea; Schnitt, Stuart J.; Tamimi, Rulla M.; Ince, Tan A.

    2014-01-01

    Accurate classification is essential for understanding the pathophysiology of a disease and can inform therapeutic choices. For hematopoietic malignancies, a classification scheme based on the phenotypic similarity between tumor cells and normal cells has been successfully used to define tumor subtypes; however, use of normal cell types as a reference by which to classify solid tumors has not been widely emulated, in part due to more limited understanding of epithelial cell differentiation compared with hematopoiesis. To provide a better definition of the subtypes of epithelial cells comprising the breast epithelium, we performed a systematic analysis of a large set of breast epithelial markers in more than 15,000 normal breast cells, which identified 11 differentiation states for normal luminal cells. We then applied information from this analysis to classify human breast tumors based on normal cell types into 4 major subtypes, HR0–HR3, which were differentiated by vitamin D, androgen, and estrogen hormone receptor (HR) expression. Examination of 3,157 human breast tumors revealed that these HR subtypes were distinct from the current classification scheme, which is based on estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Patient outcomes were best when tumors expressed all 3 hormone receptors (subtype HR3) and worst when they expressed none of the receptors (subtype HR0). Together, these data provide an ontological classification scheme associated with patient survival differences and provides actionable insights for treating breast tumors. PMID:24463450

  2. Cellular growth and survival are mediated by beta 1 integrins in normal human breast epithelium but not in breast carcinoma

    SciTech Connect

    Howlett, Anthony R; Bailey, Nina; Damsky, Caroline; Petersen, Ole W; Bissell, Mina J

    1994-11-28

    We previously established a rapid three-dimensional assay for discrimination of normal and malignant human breast epithelial cells using a laminin-rich reconstituted basement membrane. In this assay, normal epithelial cells differentiate into well-organized acinar structures whereas tumor cells fail to recapitulate this process and produce large, disordered colonies. The data suggest that breast acinar morphogenesis and differentiation is regulated by cell-extracellular matrix (ECM) interactions and that these interactions are altered in malignancy. Here, we investigated the role of ECM receptors (integrins) in these processes and report on the expression and function of potential laminin receptors in normal and tumorigenic breast epithelial cells. Immmunocytochemical analysis showed that normal and carcinoma cells in a three-dimensional substratum express profiles of integrins similar to normal and malignant breast tissues in situ. Normal cells express {alpha}1, {alpha}2, {alpha}3, {alpha}6, {beta}1 and {beta}4 integrin subunits, whereas breast carcinoma cells show variable losses, disordered expression, or down regulation of these subunits. Function-blocking experiments using inhibitory antiintegrin subunit antibodies showed a >5-fold inhibition of the formation of acinar structures by normal cells in the presence of either anti-{beta}1 or anti-{alpha}3 antibodies, whereas anti-{alpha}2 or -{alpha}6 had little or no effect. In experiments where collagen type I gels were used instead of basement membrane, acinar morphogenesis was blocked by anti-{beta}1 and -{alpha}2 antibodies but not by anti-{alpha}3. These data suggest a specificity of integrin utilization dependent on the ECM ligands encountered by the cell. The interruption of normal acinar morphogenesis by anti-integrin antibodies was associated with an inhibition of cell growth and induction of apoptosis. Function-blocking antibodies had no inhibitory effect on the rate of tumor cell growth, survival or

  3. Expression of c-kit protein in cancer vs. normal breast tissue

    PubMed Central

    Jazayeri, Seyed Nematollah; Nateghi, Jamal

    2012-01-01

    Aim of the study There are at least four main signal transduction pathways within human cells which are activated by interaction of an extracellular ligand with its corresponding receptors. One of them is activation of protein kinase. Actually, any of these proteins at any level of the signaling cascade in a human cell can undergo mutation and cause irregular cellular proliferation and finally result in cancer. C-kit is alternatively called stem cell factor receptor (SCFR) or CD117. It appears that lack of c-kit expression accompanies progression of some tumors, e.g. lung, breast, GIST. The aim of this study was to evaluate C-kit protein expression level within cancer cases. Material and methods Sixty specimens of breast cancer and 60 non-cancerous breast tissue specimens were evaluated by IHC for C-kit presentation. We used positive GIST slides as controls. Epi-info ver 6.04 (CDC, WHO) was used for analysis. Results C-kit was negative in all breast cancer specimens. C-kit was negative in 47 (78%) of 60 non-cancerous breast tissue specimens, but was positive in 13 (22%) of them (p < 0.0001). Conclusions There is a reduction in C-kit expression with malignant transformation of breast epithelium. C-kit is believed to play a role in breast carcinogenesis. However, we should follow patients with normal or benign breast tissue to indicate any correlation between C-kit presentation and breast cancer development. PMID:23788899

  4. Detection of aryl hydrocarbon hydroxylase activity in normal and neoplastic human breast epithelium

    SciTech Connect

    Greiner, J.W.; Malan-Shibley, L.B.; Janss, D.H.

    1980-01-28

    Studies were conducted to determine whether normal and/or neoplastic (MCF-7) human breast epithelial cells contain the microsomal aryl hydrocarbon hydroxylase (AHH) which catalyses the conversion of polycyclic aromatic hydrocarbons (PAH) to carcinogenic intermediates. Low constitutive levels of AHH activity were found in homogenates of both normal human breast epithelial and MCF-7 cells. The addition of 7,12-dimethylbenz(a)anthracene (DMBA) to the culture medium of either cell type significantly increased AHH activity. Peak induction of hydroxylase activity occurred following the in vitro addition of 10 ..mu..M DMBA. A time course of DMBA-induced AHH activity in both normal human breast epithelium and MCF-7 cells revealed maximal induction 16 hr after 10 ..mu..M DMBA was added to the culture medium. Benzo(a)pyrene (BP), 3-methylcholanthrene (MCA) and benz(a)anthracene (BA) also induced AHH activity in normal and MCF-7 cells. For example, the addition of 10 ..mu..M BP to the culture medium of either normal human breast epithelial or MCF-7 cells for 16 hr increased AHH activity 13.8 and 65.3-fold, respectively. For all PAH, the magnitude of AHH induction was substantially greater in MCF-7 than normal breast epithelial cells. Finally, ..cap alpha..-naphthoflavone inhibited BA-induced AHH activity in MCF-7 cells. The study demonstrates the presence of a PAH-inducible AHH enzyme(s) in normal human breast epithelial cells grown in primary culture and in the human breast tumor cell line, MCF-7.

  5. Estimation of stress relaxation time for normal and abnormal breast phantoms using optical technique

    NASA Astrophysics Data System (ADS)

    Udayakumar, K.; Sujatha, N.

    2015-03-01

    Many of the early occurring micro-anomalies in breast may transform into a deadliest cancer tumor in future. Probability of curing early occurring abnormalities in breast is more if rightly identified. Even in mammogram, considered as a golden standard technique for breast imaging, it is hard to pick up early occurring changes in the breast tissue due to the difference in mechanical behavior of the normal and abnormal tissue when subjected to compression prior to x-ray or laser exposure. In this paper, an attempt has been made to estimate the stress relaxation time of normal and abnormal breast mimicking phantom using laser speckle image correlation. Phantoms mimicking normal breast is prepared and subjected to precise mechanical compression. The phantom is illuminated by a Helium Neon laser and by using a CCD camera, a sequence of strained phantom speckle images are captured and correlated by the image mean intensity value at specific time intervals. From the relation between mean intensity versus time, tissue stress relaxation time is quantified. Experiments were repeated for phantoms with increased stiffness mimicking abnormal tissue for similar ranges of applied loading. Results shows that phantom with more stiffness representing abnormal tissue shows uniform relaxation for varying load of the selected range, whereas phantom with less stiffness representing normal tissue shows irregular behavior for varying loadings in the given range.

  6. Next-generation transcriptome sequencing of the premenopausal breast epithelium using specimens from a normal human breast tissue bank

    PubMed Central

    2014-01-01

    Introduction Our efforts to prevent and treat breast cancer are significantly impeded by a lack of knowledge of the biology and developmental genetics of the normal mammary gland. In order to provide the specimens that will facilitate such an understanding, The Susan G. Komen for the Cure Tissue Bank at the IU Simon Cancer Center (KTB) was established. The KTB is, to our knowledge, the only biorepository in the world prospectively established to collect normal, healthy breast tissue from volunteer donors. As a first initiative toward a molecular understanding of the biology and developmental genetics of the normal mammary gland, the effect of the menstrual cycle and hormonal contraceptives on DNA expression in the normal breast epithelium was examined. Methods Using normal breast tissue from 20 premenopausal donors to KTB, the changes in the mRNA of the normal breast epithelium as a function of phase of the menstrual cycle and hormonal contraception were assayed using next-generation whole transcriptome sequencing (RNA-Seq). Results In total, 255 genes representing 1.4% of all genes were deemed to have statistically significant differential expression between the two phases of the menstrual cycle. The overwhelming majority (221; 87%) of the genes have higher expression during the luteal phase. These data provide important insights into the processes occurring during each phase of the menstrual cycle. There was only a single gene significantly differentially expressed when comparing the epithelium of women using hormonal contraception to those in the luteal phase. Conclusions We have taken advantage of a unique research resource, the KTB, to complete the first-ever next-generation transcriptome sequencing of the epithelial compartment of 20 normal human breast specimens. This work has produced a comprehensive catalog of the differences in the expression of protein-coding genes as a function of the phase of the menstrual cycle. These data constitute the beginning of

  7. Estrogen Receptor-Positive Proliferating Cells in the Normal and Precancerous Breast

    PubMed Central

    Shoker, Balvinder S.; Jarvis, Christine; Clarke, Robert B.; Anderson, Elizabeth; Hewlett, Joanne; Davies, Michael P. A.; Sibson, D. Ross; Sloane, John P.

    1999-01-01

    Recently it has been shown that epithelial cell expression of the estrogen receptor (ER) and that of the proliferation-associated marker Ki-67 are almost mutually exclusive in the normal premenopausal human breast but that coexpression frequently occurs in estrogen receptor-positive (ER+) breast cancers. This coexpression may indicate disordered expression of ER in the cell cycle or failure to suppress division of ER+ cells and could be important in neoplastic transformation. The purpose of this study was to determine whether in situ proliferations known to be associated with different levels of risk for developing breast cancer contain these coexpressing cells and, if so, the stage at which they occur. We found that ER+ proliferating cells were rare in premenopausal lobules but increased with age in the normal breast. There was no difference in nonlesional tissue between cancerous and noncancerous breasts. The percentage of dual-expressing cells was significantly increased, however, in all of the in situ proliferations and correlated positively with the level of risk of developing breast cancer. We suggest that development of at least some human breast cancers is associated with increasing failure to down-regulate ER as cells enter the cycle or to suppress division of ER+ cells. The mechanism may involve the loss of a tumor suppresser gene. PMID:10595909

  8. Assessment of quantitative and qualitative changes of proteoglycans and glycosaminoglycans in normal breast tissue during the follicular and luteal phases of the menstrual cycle.

    PubMed

    Júnior, J A Dos Santos; de Lima, C R; Michelacci, Y M C da Silva; Nazário, A C Pinto

    2015-01-01

    The effect of sex hormones on extracellular matrix compounds, such as proteoglycans (PGs) and glycosaminoglycans (GAGs), in mammary tissue remains poorly understood. The elucidation of extracellular matrix component functions could clarify pathophysiological conditions, such as cyclical mastalgia (breast pain). The authors examined the quantitative and qualitative changes of PGs and GAGs in normal breast tissue during the follicular and luteal phases of the menstrual cycle. Twenty-eight eumenorrheic patients with benign breast nodules were divided into groups: Group A included 15 follicular patients and Group B included 13 luteal phase patients. Breast tissue adjacent to the nodules was biochemically analyzed to evaluate the types and concentrations of PGS and GAGs. The distribution of proteoglycans during the menstrual cycle was analyzed with immunofluorescence. PG concentrations were elevated (p < 0.01) during the luteal phase compared with the follicular phase, whereas the concentrations of GAGs did not differ significantly. Immunofluorescence revealed that decorin was mainly found in the intralobular stroma. PG concentrations were elevated during the luteal phase, likely due to the influence of sex hormones on macromolecular synthesis. The PG decorin was observed in normal breast tissue in the intralobular stroma. Although the concentration of GAGs, including dermatan and heparan sulfate, varied cyclically, the differences were not significant.

  9. Combined thermal and elastic modeling of the normal and tumorous breast

    NASA Astrophysics Data System (ADS)

    Jiang, Li; Zhan, Wang; Loew, Murray

    2008-03-01

    The abnormal thermogram has been shown to be a reliable indicator of a high risk of breast cancer, but an open question is how to quantify the complex relationships between the breast thermal behaviors and the underlying physiological/pathological conditions. Previous thermal modeling techniques generally did not utilize the breast geometry determined by the gravity-induced elastic deformations arising from various body postures. In this paper, a 3-D finite-element method is developed for combined modeling of the thermal and elastic properties of the breast, including the mechanical nonlinearity associated with large deformations. The effects of the thermal and elastic properties of the breast tissues are investigated quantitatively. For the normal breast in a standing/sitting up posture, the gravity-induced deformation alone is found to be able to cause an asymmetric temperature distribution even though all the thermal/elastic properties are symmetrical, and this temperature asymmetry increases for softer and more compressible breast tissues. For a tumorous breast, we found that the surface-temperature alterations generally can be recognizable for superficial tumors at depths less than 20 mm. Tumor size plays a less important role than the tumor depth in determining the tumor-induced temperature difference. This result may imply that a higher thermal sensitivity is critical for a breast thermogram system when deeper tumors are present, even if the tumor is relatively large. We expect this new method to provide a stronger foundation for, and greater specificity and precision in, thermographic diagnosis and treatment of breast tumors.

  10. Sarcoglycans in the normal and pathological breast tissue of humans: an immunohistochemical and molecular study.

    PubMed

    Arco, Alba; Favaloro, Angelo; Gioffrè, Mara; Santoro, Giuseppe; Speciale, Francesco; Vermiglio, Giovanna; Cutroneo, Giuseppina

    2012-01-01

    The sarcoglycan complex, consisting of α-, β-, γ-, δ- and ε-sarcoglycans, is a multimember transmembrane system providing a mechanosignaling connection from the cytoskeleton to the extracellular matrix. Whereas the expression of α- and γ-sarcoglycan is restricted to striated muscle, other sarcoglycans are widely expressed. Although many studies have investigated sarcoglycans in all muscle types, insufficient data are available on the distribution of the sarcoglycan complex in nonmuscle tissue. On this basis, we used immunohistochemical and RT-PCR techniques to study preliminarily the sarcoglycans in normal glandular breast tissue (which has never been studied in the literature on these proteins) to verify the effective wider distribution of this complex. Moreover, to understand the role of sarcoglycans, we also tested samples obtained from patients affected by fibrocystic mastopathy and breast fibroadenoma. Our data showed, for the first time, that all sarcoglycans are always detectable in all normal samples both in epithelial and myoepithelial cells; in pathological breast tissue, all sarcoglycans appeared severely reduced. These data demonstrated that all sarcoglycans, not only β-, δ-, and ε-sarcoglycans, have a wider distribution, implying a new unknown role for these proteins. Moreover, in breast diseases, sarcoglycans containing cadherin domain homologs could provoke a loss of strong adhesion between epithelial cells, permitting and facilitating the degeneration of these benign breast tumors into malignant tumors. Consequently, sarcoglycans could play an important and intriguing role in many breast diseases and in particular in tumor progression from benign to malignant.

  11. Cyclooxygenase-2 expression is related to nuclear grade in ductal carcinoma in situ and is increased in its normal adjacent epithelium

    NASA Technical Reports Server (NTRS)

    Shim, Veronica; Gauthier, Mona L.; Sudilovsky, Daniel; Mantei, Kristin; Chew, Karen L.; Moore, Dan H.; Cha, Imok; Tlsty, Thea D.; Esserman, Laura J.

    2003-01-01

    Cyclooxygenase-2 (COX-2) is emerging as an important cancer biomarker and is now an experimental target for solid tumor treatment.However, no study has exclusively focused on COX-2 expression in early lesions such as ductal carcinoma in situ (DCIS). We examined COX-2 expression by immunohistochemistry in 46 cases of women undergoing surgical resection for DCIS. We found that COX-2 expression was detected in 85% of all DCIS specimens, with increased COX-2 staining correlating with higher nuclear grade. Strikingly, COX-2 staining intensity in the normal adjacent epithelium was stronger than in the DCIS lesion itself. Our observations demonstrate that COX-2 is up-regulated in the normal adjacent epithelium and supports the hypothesis that the surrounding epithelial tissue is part of the disease process in DCIS.

  12. Mitochondria “fuel” breast cancer metabolism: Fifteen markers of mitochondrial biogenesis label epithelial cancer cells, but are excluded from adjacent stromal cells

    PubMed Central

    Sotgia, Federica; Whitaker-Menezes, Diana; Martinez-Outschoorn, Ubaldo E.; Salem, Ahmed F.; Tsirigos, Aristotelis; Lamb, Rebecca; Sneddon, Sharon; Hulit, James; Howell, Anthony; Lisanti, Michael P.

    2012-01-01

    Here, we present new genetic and morphological evidence that human tumors consist of two distinct metabolic compartments. First, re-analysis of genome-wide transcriptional profiling data revealed that > 95 gene transcripts associated with mitochondrial biogenesis and/or mitochondrial translation were significantly elevated in human breast cancer cells, as compared with adjacent stromal tissue. Remarkably, nearly 40 of these upregulated gene transcripts were mitochondrial ribosomal proteins (MRPs), functionally associated with mitochondrial translation of protein components of the OXPHOS complex. Second, during validation by immunohistochemistry, we observed that antibodies directed against 15 markers of mitochondrial biogenesis and/or mitochondrial translation (AKAP1, GOLPH3, GOLPH3L, MCT1, MRPL40, MRPS7, MRPS15, MRPS22, NRF1, NRF2, PGC1-α, POLRMT, TFAM, TIMM9 and TOMM70A) selectively labeled epithelial breast cancer cells. These same mitochondrial markers were largely absent or excluded from adjacent tumor stromal cells. Finally, markers of mitochondrial lipid synthesis (GOLPH3) and mitochondrial translation (POLRMT) were associated with poor clinical outcome in human breast cancer patients. Thus, we conclude that human breast cancers contain two distinct metabolic compartments—a glycolytic tumor stroma, which surrounds oxidative epithelial cancer cells—that are mitochondria-rich. The co-existence of these two compartments is indicative of metabolic symbiosis between epithelial cancer cells and their surrounding stroma. As such, epithelial breast cancer cells should be viewed as predatory metabolic “parasites,” which undergo anabolic reprogramming to amplify their mitochondrial “power.” This notion is consistent with the observation that the anti-malarial agent chloroquine may be an effective anticancer agent. New anticancer therapies should be developed to target mitochondrial biogenesis and/or mitochondrial translation in human cancer cells. PMID

  13. From The Cover: Reconstruction of functionally normal and malignant human breast tissues in mice

    NASA Astrophysics Data System (ADS)

    Kuperwasser, Charlotte; Chavarria, Tony; Wu, Min; Magrane, Greg; Gray, Joe W.; Carey, Loucinda; Richardson, Andrea; Weinberg, Robert A.

    2004-04-01

    The study of normal breast epithelial morphogenesis and carcinogenesis in vivo has largely used rodent models. Efforts at studying mammary morphogenesis and cancer with xenotransplanted human epithelial cells have failed to recapitulate the full extent of development seen in the human breast. We have developed an orthotopic xenograft model in which both the stromal and epithelial components of the reconstructed mammary gland are of human origin. Genetic modification of human stromal cells before the implantation of ostensibly normal human mammary epithelial cells resulted in the outgrowth of benign and malignant lesions. This experimental model allows for studies of human epithelial morphogenesis and differentiation in vivo and underscores the critical role of heterotypic interactions in human breast development and carcinogenesis.

  14. Variability of glutathione S-transferase isoenzyme patterns in matched normal and cancer human breast tissue.

    PubMed Central

    Kelley, M K; Engqvist-Goldstein, A; Montali, J A; Wheatley, J B; Schmidt, D E; Kauvar, L M

    1994-01-01

    The determination of GST levels in blood has been proposed to a marker of tumour burden in general, whereas level of the P1 isoenzyme has been identified as a prognostic factor for breast-cancer patients receiving no adjuvant chemotherapy. Particular glutathione S-transferase (GST) isoenzymes differ in their substrate specificity, however, and their presence or absence might therefore account for the resistance of tumours to particular chemotherapeutic drugs, as already established for cultured cell lines. Determination of the GST isoenzyme profile of a cancer tissue could have prognostic value in the selection of treatment if the levels of expression/activity show a degree of variation comparable with that exhibited by actual patient responses. Using reversed-phase h.p.l.c. to quantify affinity-isolated GSTs, we have analysed full isoenzyme profiles in the first large sample of matched normal and cancer human tissues (18 breast-cancer patients). In no patients did the tumour tissues express any isoenzymes that were not found in normal breast tissue. In addition to the GSTs, another enzyme, identified as enoyl-CoA isomerase, was regularly found in breast tissue cytosol following elution from a hexyl-glutathione affinity column. In most cases, the average level of GST was substantially elevated in the cancer tissues above the levels in normal breast tissue from the same patient. Furthermore, the relative levels of the isoenzymes were substantially more variable in the cancer samples than in the normal breast tissue, providing a plausible mechanism for the well established variable response to treatment. Images Figure 1 Figure 3 PMID:7818489

  15. Unraveling the microenvironmental influences on the normal mammary gland and induction and progression of breast cancer

    SciTech Connect

    Weigelt, Britta; Bissell, Mina J.

    2008-06-26

    The normal mammary gland and invasive breast cancer are both complex 'organs' composed of multiple cell types as well as extracellular matrix (ECM) in three-dimensional (3D) space. Conventionally, both normal and malignant breast cells are studied in vitro as two-dimensional (2D) monolayers of epithelial cells, which results in the loss of structure and tissue function. Many laboratories are now investigating regulation of signaling function in normal mammary gland using 3D cultures. However, it is important also to assay malignant breast cells ex vivo in a physiologically relevant environment to more closely mimic tumor architecture, signal transduction regulation and tumor behavior in vivo. Here we present the potential of these 3D models for drug testing, target validation and guidance of patient selection for clinical trials. We argue also that in order to get full insight into the biology of the normal and malignant breast, and to create in vivo-like models for therapeutic approaches in humans, we need to continue to create more complex heterotypic models to approach the full context the cells encounter in the human body.

  16. [Trace and anxiety of nursing mothers with insufficient and normal breast feeding indicators].

    PubMed

    Aragaki, Ilva Marico Mizumoto; Silva, Isília Aparecida; dos Santos, Jair Lício Ferreira

    2006-09-01

    The objective of this study was to identify and compare the trace and the anxiety state on the 10th day postpartum and the anxiety state on the 30th day postpartum of primiparous and multiparous nursing mothers who present insufficient breast feeding indicators and nursing mothers with normal breast feeding, in order to verify the possible relationships between the anxiety state of the nursing mothers in those two moments with the insufficient breast feeding indicators presented. This is an exploratory and descriptive study, whose data has been gotten from 168 nursing mothers and their children by means of interviews in nursing consultations in the 10th and 30th day postpartum. The results obtained showed that primiparous and multiparous with insufficient breast feeding and primiparous with normal lactation presented higher anxiety state trace than the anxiety state on the 10th and 30th day postpartum. There was remission of the maternal signals of anxiety with the passing of time, which may be caused by the correction of the breast feeding technique and support to the nursing mothers.

  17. Signaling pathways regulating aromatase and cyclooxygenases in normal and malignant breast cells.

    PubMed

    Richards, Jeanette A; Petrel, Trevor A; Brueggemeier, Robert W

    2002-02-01

    Aromatase (estrogen synthase) is the cytochrome P450 enzyme complex that converts C(19) androgens to C(18) estrogens. Aromatase activity has been demonstrated in breast tissue in vitro, and expression of aromatase is highest in or near breast tumor sites. Thus, local regulation of aromatase by both endogenous factors as well as exogenous medicinal agents will influence the levels of estrogen available for breast cancer growth. The prostaglandin PGE(2) increases intracellular cAMP levels and stimulates estrogen biosynthesis, and our recent studies have shown a strong linear association between CYP19 expression and the sum of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) expression in breast cancer specimens. Knowledge of the signaling pathways that regulate the expression and enzyme activity of aromatase and cyclooxygenases (COXs) in stromal and epithelial breast cells will aid in understanding the interrelationships of these two enzyme systems and potentially identify novel targets for regulation. The effects of epidermal growth factor (EGF), transforming growth factor-beta (TGFbeta), and tetradecanoyl phorbol acetate (TPA) on aromatase and COXs were studied in primary cultures of normal human adipose stromal cells and in cell cultures of normal immortalized human breast epithelial cells MCF-10F, estrogen-responsive human breast cancer cells MCF-7, and estrogen-unresponsive human breast cancer cells MDA-MB-231. Levels of the constitutive COX isozyme, COX-1, were not altered by the various treatments in the cell systems studied. In breast adenocarcinoma cells, EGF and TGFbeta did not alter COX-2 levels at 24h, while TPA induced COX-2 levels by 75% in MDA-MB-231 cells. EGF and TPA in MCF-7 cells significantly increased aromatase activity while TGFbeta did not. In contrast to MCF-7 cells, TGFbeta and TPA significantly increased activity in MDA-MB-231 cells, while only a modest increase with EGF was observed. Untreated normal adipose stromal cells exhibited

  18. PMC42, a breast progenitor cancer cell line, has normal-like mRNA and microRNA transcriptomes

    PubMed Central

    Git, Anna; Spiteri, Inmaculada; Blenkiron, Cherie; Dunning, Mark J; Pole, Jessica CM; Chin, Suet-Feung; Wang, Yanzhong; Smith, James; Livesey, Frederick J; Caldas, Carlos

    2008-01-01

    Introduction The use of cultured cell lines as model systems for normal tissue is limited by the molecular alterations accompanying the immortalisation process, including changes in the mRNA and microRNA (miRNA) repertoire. Therefore, identification of cell lines with normal-like expression profiles is of paramount importance in studies of normal gene regulation. Methods The mRNA and miRNA expression profiles of several breast cell lines of cancerous or normal origin were measured using printed slide arrays, Luminex bead arrays, and real-time reverse transcription-polymerase chain reaction. Results We demonstrate that the mRNA expression profiles of two breast cell lines are similar to that of normal breast tissue: HB4a, immortalised normal breast epithelium, and PMC42, a breast cancer cell line that retains progenitor pluripotency allowing in-culture differentiation to both secretory and myoepithelial fates. In contrast, only PMC42 exhibits a normal-like miRNA expression profile. We identified a group of miRNAs that are highly expressed in normal breast tissue and PMC42 but are lost in all other cancerous and normal-origin breast cell lines and observed a similar loss in immortalised lymphoblastoid cell lines compared with healthy uncultured B cells. Moreover, like tumour suppressor genes, these miRNAs are lost in a variety of tumours. We show that the mechanism leading to the loss of these miRNAs in breast cancer cell lines has genomic, transcriptional, and post-transcriptional components. Conclusion We propose that, despite its neoplastic origin, PMC42 is an excellent molecular model for normal breast epithelium, providing a unique tool to study breast differentiation and the function of key miRNAs that are typically lost in cancer. PMID:18588681

  19. Expression of ecto-5'-nucleotidase (CD73) in normal mammary gland and in breast carcinoma.

    PubMed Central

    Krüger, K. H.; Thompson, L. F.; Kaufmann, M.; Möller, P.

    1991-01-01

    Ecto-5'-nucleotidase (ecto-5'-NT) is a phosphatidylinositol anchored membrane structure recently defined as the lymphocyte differentiation antigen CD73. Using CD73 (1E9.28.1) monoclonal antibody, normal mammary gland and breast carcinoma were immunohistochemically investigated for ecto-5'-NT expression. In normal breast epithelium, CD73 was differentially expressed in lobular, ductal and myoepithelial cells and was most frequently detected in the myoepithelial compartment. The glandular stroma contained fibrocytes, a subset of which was also CD73-positive. Among 102 unselected breast carcinoma primary lesions, only 9 contained CD73-positive tumour cells, whereas in 95 cases, stromal fibroblasts and fibrocytes showed variable degrees of CD73 expression. The extent of stromal CD73 expression correlated positively with the estrogen receptor (ER) status of the tumour (P less than 0.038). We conclude that ecto-5'-NT-expression reflects a still unknown state of activity of normal breast epithelium which is lost in the majority of carcinomas derived therefrom. It may also be indicative of some functional activity of stromal fibroblasts which is significantly enhanced in ER-positive carcinomas. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:1989648

  20. Breast Cancer Heterogeneity Examined by High-Sensitivity Quantification of PIK3CA, KRAS, HRAS, and BRAF Mutations in Normal Breast and Ductal Carcinomas.

    PubMed

    Myers, Meagan B; Banda, Malathi; McKim, Karen L; Wang, Yiying; Powell, Michael J; Parsons, Barbara L

    2016-04-01

    Mutant cancer subpopulations have the potential to derail durable patient responses to molecularly targeted cancer therapeutics, yet the prevalence and size of such subpopulations are largely unexplored. We employed the sensitive and quantitative Allele-specific Competitive Blocker PCR approach to characterize mutant cancer subpopulations in ductal carcinomas (DCs), examining five specific hotspot point mutations (PIK3CA H1047R, KRAS G12D, KRAS G12V, HRAS G12D, and BRAF V600E). As an approach to aid interpretation of the DC results, the mutations were also quantified in normal breast tissue. Overall, the mutations were prevalent in normal breast and DCs, with 9/9 DCs having measureable levels of at least three of the five mutations. HRAS G12D was significantly increased in DCs as compared to normal breast. The most frequent point mutation reported in DC by DNA sequencing, PIK3CA H1047R, was detected in all normal breast tissue and DC samples and was present at remarkably high levels (mutant fractions of 1.1 × 10(-3) to 4.6 × 10(-2)) in 4/10 normal breast samples. In normal breast tissue samples, PIK3CA mutation levels were positively correlated with age. However, the PIK3CA H1047R mutant fraction distributions for normal breast tissues and DCs were similar. The results suggest PIK3CA H1047R mutant cells have a selective advantage in breast, contribute to breast cancer susceptibility, and drive tumor progression during breast carcinogenesis, even when present as only a subpopulation of tumor cells. PMID:27108388

  1. Pleomorphic adenoma of the breast should be excised with a cuff of normal tissue.

    PubMed

    John, Biku J; Griffiths, Carl; Ebbs, Steven R

    2007-01-01

    Pleomorphic adenoma is a benign tumor found rarely in the breast but commonly in the salivary gland. Unlike the salivary gland variant management guidelines are poorly defined in the breast. We describe the first case of pleomorphic adenoma of the breast that has recurred for the second time following previous surgical excisions, and review the available literature. Due to the risk of recurrence and malignant transformation, we recommend complete excision of the lesion with a cuff of normal tissue, as is the practice in the salivary gland. Clinicians should be aware of the condition, as preoperative diagnosis will facilitate adequate surgery. Patients should be informed about the risk of recurrence. We recommend follow-up for at least a period of 5 years with yearly clinical examinations.

  2. Comparison of gene regulatory networks of benign and malignant breast cancer samples with normal samples.

    PubMed

    Chen, D B; Yang, H J

    2014-11-11

    The aim of this study was to explain the pathogenesis and deterioration process of breast cancer. Breast cancer expression profile data GSE27567 was downloaded from the Gene Expression Omnibus (GEO) database, and breast cancer-related genes were extracted from databases, including Cancer-Resource and Online Mendelian Inheritance In Man (OMIM). Next, h17 transcription factor data were obtained from the University of California, Santa Cruz. Database for Annotation, Visualization, and Integrated Discovery (DAVID)-enrichment analysis was applied and gene-regulatory networks were constructed by double-two-way t-tests in 3 states, including normal, benign, and malignant. Furthermore, network topological properties were compared between 2 states, and breast cancer-related bub genes were ranked according to their different degrees between each of the two states. A total of 2380 breast cancer-related genes and 215 transcription factors were screened by exploring databases; the genes were mainly enriched in their functions, such as cell apoptosis and proliferation, and pathways, such as p53 signaling and apoptosis, which were related with carcinogenesis. In addition, gene-regulatory networks in the 3 conditions were constructed. By comparing their network topological properties, we found that there is a larger transition of differences between malignant and benign breast cancer. Moreover, 8 hub genes (YBX1, ZFP36, YY1, XRCC5, XRCC4, ZFHX3, ZMAT3, and XPC) were identified in the top 10 genes ranked by different degrees. Through comparative analysis of gene-regulation networks, we identified the link between related genes and the pathogenesis of breast cancer. However, further experiments are needed to confirm our results.

  3. Prolyl-isomerase Pin1 controls normal and cancer stem cells of the breast

    PubMed Central

    Rustighi, Alessandra; Zannini, Alessandro; Tiberi, Luca; Sommaggio, Roberta; Piazza, Silvano; Sorrentino, Giovanni; Nuzzo, Simona; Tuscano, Antonella; Eterno, Vincenzo; Benvenuti, Federica; Santarpia, Libero; Aifantis, Iannis; Rosato, Antonio; Bicciato, Silvio; Zambelli, Alberto; Del Sal, Giannino

    2014-01-01

    Mammary epithelial stem cells are fundamental to maintain tissue integrity. Cancer stem cells (CSCs) are implicated in both treatment resistance and disease relapse, and the molecular bases of their malignant properties are still poorly understood. Here we show that both normal stem cells and CSCs of the breast are controlled by the prolyl-isomerase Pin1. Mechanistically, following interaction with Pin1, Notch1 and Notch4, key regulators of cell fate, escape from proteasomal degradation by their major ubiquitin-ligase Fbxw7α. Functionally, we show that Fbxw7α acts as an essential negative regulator of breast CSCs' expansion by restraining Notch activity, but the establishment of a Notch/Pin1 active circuitry opposes this effect, thus promoting breast CSCs self-renewal, tumor growth and metastasis in vivo. In human breast cancers, despite Fbxw7α expression, high levels of Pin1 sustain Notch signaling, which correlates with poor prognosis. Suppression of Pin1 holds promise in reverting aggressive phenotypes, through CSC exhaustion as well as recovered drug sensitivity carrying relevant implications for therapy of breast cancers. PMID:24357640

  4. In vivo quantitative imaging of normal and cancerous breast tissue using broadband diffuse optical tomography

    PubMed Central

    Wang, Jia; Jiang, Shudong; Li, Zhongze; diFlorio-Alexander, Roberta M.; Barth, Richard J.; Kaufman, Peter A.; Pogue, Brian W.; Paulsen, Keith D.

    2010-01-01

    Purpose: A NIR tomography system that combines frequency domain (FD) and continuous wave (CW) measurements was used to image normal and malignant breast tissues. Methods: FD acquisitions were confined to wavelengths less than 850 nm because of detector limitations, whereas light from longer wavelengths (up to 948 nm) was measured in CW mode with CCD-coupled spectrometer detection. The two data sets were combined and processed in a single spectrally constrained reconstruction to map concentrations of hemoglobin, water, and lipid, as well as scattering parameters in the breast. Results: Chromophore concentrations were imaged in the breasts of nine asymptomatic volunteers to evaluate their intrasubject and intersubject variability. Normal subject data showed physiologically expected trends. Images from three cancer patients indicate that the added CW data is critical to recovering the expected increases in water and decreases in lipid content within malignancies. Contrasts of 1.5 to twofold in hemoglobin and water values were found in cancers. Conclusions:In vivo breast imaging with instrumentation that combines FD and CW NIR data acquisition in a single spectral reconstruction produces more accurate hemoglobin, water, and lipid results relative to FD data alone. PMID:20831079

  5. Propagation of oestrogen receptor-positive and oestrogen-responsive normal human breast cells in culture

    PubMed Central

    Fridriksdottir, Agla J.; Kim, Jiyoung; Villadsen, René; Klitgaard, Marie Christine; Hopkinson, Branden M.; Petersen, Ole William; Rønnov-Jessen, Lone

    2015-01-01

    Investigating the susceptibility of oestrogen receptor-positive (ERpos) normal human breast epithelial cells (HBECs) for clinical purposes or basic research awaits a proficient cell-based assay. Here we set out to identify markers for isolating ERpos cells and to expand what appear to be post-mitotic primary cells into exponentially growing cultures. We report a robust technique for isolating ERpos HBECs from reduction mammoplasties by FACS using two cell surface markers, CD166 and CD117, and an intracellular cytokeratin marker, Ks20.8, for further tracking single cells in culture. We show that ERpos HBECs are released from growth restraint by small molecule inhibitors of TGFβ signalling, and that growth is augmented further in response to oestrogen. Importantly, ER signalling is functionally active in ERpos cells in extended culture. These findings open a new avenue of experimentation with normal ERpos HBECs and provide a basis for understanding the evolution of human breast cancer. PMID:26564780

  6. Tumor-induced solid stress activates β-catenin signaling to drive malignant behavior in normal, tumor-adjacent cells

    PubMed Central

    Ou, Guanqing; Weaver, Valerie Marie

    2016-01-01

    Recent work by Fernández-Sánchez and coworkers examining the impact of applied pressure on the malignant phenotype of murine colon tissue in vivo revealed that mechanical perturbations can drive malignant behavior in genetically normal cells. Their findings build upon an existing understanding of how the mechanical cues experienced by cells within a tissue become progressively modified as the tissue transforms. Using magnetically stimulated ultra-magnetic liposomes to mimic tumor growth -induced solid stress, Fernández-Sánchez and coworkers were able to stimulate β-catenin to promote the cancerous behavior of both a normal and genetically modified colon epithelium. In this perspective, we discuss their findings in the context of what is currently known regarding the role of the mechanical landscape in cancer progression and β-catenin as a mechanotransducer. We review data that suggest that mechanically regulated activation of β-catenin fosters development of a malignant phenotype in tissue and predict that mechanical cues may contribute to tumor heterogeneity. PMID:26439949

  7. Ultrasonic differentiation of normal versus malignant breast epithelial cells in monolayer cultures

    PubMed Central

    Doyle, Timothy E.; Goodrich, Jeffrey B.; Ambrose, Brady J.; Patel, Hemang; Kwon, Soonjo; Pearson, Lee H.

    2010-01-01

    Normal and malignant mammary epithelial cells were studied using laboratory measurements, wavelet analysis, and numerical simulations of monolayer cell cultures to determine whether microscopic breast cancer can be detected in vitro with high-frequency ultrasound. Pulse-echo waveforms were acquired by immersing a broadband, unfocused 50-MHz transducer in the growth media of cell culture well plates and collecting the first reflection from the well bottoms. The simulations included a multilayer pulse-reflection model and a model of two-dimensional arrays of spherical cells and nuclei. The results show that normal and malignant cells produce time-domain signals and spectral features that are significantly different. PMID:21110531

  8. Classification of breast masses and normal tissues in digital tomosynthesis mammography

    NASA Astrophysics Data System (ADS)

    Wei, Jun; Chan, Heang-Ping; Zhang, Yiheng; Sahiner, Berkman; Zhou, Chuan; Ge, Jun; Wu, Yi-Ta; Hadjiiski, Lubomir M.

    2008-03-01

    Digital tomosynthesis mammography (DTM) can provide quasi-3D structural information of the breast by reconstructing the breast volume from projection views (PV) acquired in a limited angular range. Our purpose is to design an effective classifier to distinguish breast masses from normal tissues in DTMs. A data set of 100 DTM cases collected with a GE first generation prototype DTM system at the Massachusetts General Hospital was used. We reconstructed the DTMs using a simultaneous algebraic reconstruction technique (SART). Mass candidates were identified by 3D gradient field analysis. Three approaches to distinguish breast masses from normal tissues were evaluated. In the 3D approach, we extracted morphological and run-length statistics texture features from DTM slices as input to a linear discriminant analysis (LDA) classifier. In the 2D approach, the raw input PVs were first preprocessed with a Laplacian pyramid multi-resolution enhancement scheme. A mass candidate was then forward-projected to the preprocessed PVs in order to determine the corresponding regions of interest (ROIs). Spatial gray-level dependence (SGLD) texture features were extracted from each ROI and averaged over 11 PVs. An LDA classifier was designed to distinguish the masses from normal tissues. In the combined approach, the LDA scores from the 3D and 2D approaches were averaged to generate a mass likelihood score for each candidate. The A z values were 0.87+/-0.02, 0.86+/-0.02, and 0.91+/-0.02 for the 3D, 2D, and combined approaches, respectively. The difference between the A z values of the 3D and 2D approaches did not achieve statistical significance. The performance of the combined approach was significantly (p<0.05) better than either the 3D or 2D approach alone. The combined classifier will be useful for false-positive reduction in computerized mass detection in DTM.

  9. Role of microRNA221 in regulating normal mammary epithelial hierarchy and breast cancer stem-like cells

    PubMed Central

    Hong, Su-Hyung; Bai, Shoumin; He, Zhen; Malik, Fayaz; Xu, Jiahui; Zhou, Lei; Chen, Weilong; Martin-Trevino, Rachel; Wu, Xiaojian; Lan, Ping; Yi, Yongju; Ginestier, Christophe; Ibarra, Ingrid; Shang, Li; McDermott, Sean; Luther, Tahra; Clouthier, Shawn G.; Wicha, Max S.; Liu, Suling

    2015-01-01

    Increasing evidence suggests that lineage specific subpopulations and stem-like cells exist in normal and malignant breast tissues. Epigenetic mechanisms maintaining this hierarchical homeostasis remain to be investigated. In this study, we found the level of microRNA221 (miR-221) was higher in stem-like and myoepithelial cells than in luminal cells isolated from normal and malignant breast tissue. In normal breast cells, over-expression of miR-221 generated more myoepithelial cells whereas knock-down of miR-221 increased luminal cells. Over-expression of miR-221 stimulated stem-like cells in luminal type of cancer and the miR-221 level was correlated with clinical outcome in breast cancer patients. Epithelial-mesenchymal transition (EMT) was induced by overexpression of miR-221 in normal and breast cancer cells. The EMT related gene ATXN1 was found to be a miR-221 target gene regulating breast cell hierarchy. In conclusion, we propose that miR-221 contributes to lineage homeostasis of normal and malignant breast epithelium. PMID:25686829

  10. Photoacoustic spectroscopy based investigatory approach to discriminate breast cancer from normal: a pilot study

    NASA Astrophysics Data System (ADS)

    Priya, Mallika; Rao, Bola Sadashiva Satish; Chandra, Subhash; Ray, Satadru; Mathew, Stanley; Datta, Anirbit; Nayak, Subramanya G.; Mahato, Krishna Kishore

    2016-02-01

    In spite of many efforts for early detection of breast cancer, there is still lack of technology for immediate implementation. In the present study, the potential photoacoustic spectroscopy was evaluated in discriminating breast cancer from normal, involving blood serum samples seeking early detection. Three photoacoustic spectra in time domain were recorded from each of 20 normal and 20 malignant samples at 281nm pulsed laser excitations and a total of 120 spectra were generated. The time domain spectra were then Fast Fourier Transformed into frequency domain and 116.5625 - 206.875 kHz region was selected for further analysis using a combinational approach of wavelet, PCA and logistic regression. Initially, wavelet analysis was performed on the FFT data and seven features (mean, median, area under the curve, variance, standard deviation, skewness and kurtosis) from each were extracted. PCA was then performed on the feature matrix (7x120) for discriminating malignant samples from the normal by plotting a decision boundary using logistic regression analysis. The unsupervised mode of classification used in the present study yielded specificity and sensitivity values of 100% in each respectively with a ROC - AUC value of 1. The results obtained have clearly demonstrated the capability of photoacoustic spectroscopy in discriminating cancer from the normal, suggesting its possible clinical implications.

  11. Lipid Profiles of Canine Invasive Transitional Cell Carcinoma of the Urinary Bladder and Adjacent Normal Tissue by Desorption Electrospray Ionization Imaging Mass Spectrometry

    PubMed Central

    Dill, Allison L.; Ifa, Demian R.; Manicke, Nicholas E.; Costa, Anthony B.; Ramos-Vara, José A.; Knapp, Deborah W.; Cooks, R. Graham

    2009-01-01

    Desorption electrospray ionization (DESI) mass spectrometry (MS) was used in an imaging mode to interrogate the lipid profiles of thin tissue sections of canine spontaneous invasive transitional cell carcinoma (TCC) of the urinary bladder (a model of human invasive bladder cancer) as well as adjacent normal tissue from four different dogs. The glycerophospholipids and sphingolipids that appear as intense signals in both the negative ion and positive ion modes were identified by tandem mass spectrometry (MS/MS) product ion scans using collision-induced dissociation. Differences in the relative distributions of the lipid species were present between the tumor and adjacent normal tissue in both the negative and positive ion modes. DESI-MS images showing the spatial distributions of particular glycerophospholipids, sphinoglipids and free fatty acids in both the negative and positive ion modes were compared to serial tissue sections that were stained with hematoxylin and eosin (H&E). Increased absolute and relative intensities for at least five different glycerophospholipids and three free fatty acids in the negative ion mode and at least four different lipid species in the positive ion mode were seen in the tumor region of the samples in all four dogs. In addition, one sphingolipid species exhibited increased signal intensity in the positive ion mode in normal tissue relative to the diseased tissue. Principal component analysis (PCA) was also used to generate unsupervised statistical images from the negative ion mode data and these images are in excellent agreement with the DESI images obtained from the selected ions and also the H&E stained tissue PMID:19810710

  12. Influence of menstrual cycle, parity and oral contraceptive use on steroid hormone receptors in normal breast.

    PubMed Central

    Battersby, S.; Robertson, B. J.; Anderson, T. J.; King, R. J.; McPherson, K.

    1992-01-01

    Steroid receptor was assessed immunohistochemically in 158 samples of normal breast for variation through the menstrual cycle. Patterns and intensity of reaction were used in a semi-quantitative scoring system to examine the influence of cycle phase, cycle type, parity and age. The changes in oestrogen receptor for natural cycle and oral contraceptive (OC) cycles indicated down-regulation by progestins. Progesterone receptor did not vary significantly in natural cycles, but increased steadily through OC cycles. This study provides strong evidence that both oestrogen and progesterone influence breast epithelium, but dissimilarities from the endometrium are apparent. The interval since pregnancy had a significant negative effect on frequency and score of oestrogen receptor and score of progesterone receptor. Multivariate analysis established the phase of cycle and OC use as independent significant influences on oestrogen receptor. The interval since pregnancy was an independent significant factor for both oestrogen and progesterone receptor presence. Images Figure 1 Figure 2 PMID:1562470

  13. Gene expression in normal-appearing tissue adjacent to prostate cancers are predictive of clinical outcome: evidence for a biologically meaningful field effect

    PubMed Central

    Magi-Galluzzi, Cristina; Maddala, Tara; Falzarano, Sara Moscovita; Cherbavaz, Diana B.; Zhang, Nan; Knezevic, Dejan; Febbo, Phillip G.; Lee, Mark; Lawrence, Hugh Jeffrey; Klein, Eric A.

    2016-01-01

    Purpose We evaluated gene expression in histologically normal-appearing tissue (NT) adjacent to prostate tumor in radical prostatectomy specimens, assessing for biological significance based on prediction of clinical recurrence (cR - metastatic disease or local recurrence). Results A total of 410 evaluable patients had paired tumor and NT. Fortysix genes, representing diverse biological pathways (androgen signaling, stromal response, stress response, cellular organization, proliferation, cell adhesion, and chromatin remodeling) were associated with cR in NT (FDR < 20%), of which 39 concordantly predicted cR in tumor (FDR < 20%). Overall GPS and its stromal response and androgen-signaling gene group components also significantly predicted time to cR in NT (RM-corrected HR/20 units = 1.25; 95% CI: 1.01-1.56; P = 0.024). Experimental Design Expression of 732 genes was measured by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) separately in tumor and adjacent NT specimens from 127 patients with and 374 without cR following radical prostatectomy for T1/T2 prostate cancer. A 17-gene expression signature (Genomic Prostate Score [GPS]), previously validated to predict aggressive prostate cancer when measured in tumor tissue, was also assessed using pre-specified genes and algorithms. Analysis used Cox proportional hazards models, Storey's false discovery rate (FDR) control, and regression to the mean (RM) correction. Conclusions Gene expression profiles, including GPS, from NT adjacent to tumor can predict prostate cancer outcome. These findings suggest that there is a biologically significant field effect in primary prostate cancer that is a marker for aggressive disease. PMID:27121323

  14. Differential expression of WISP-1 and WISP-2 genes in normal and transformed human breast cell lines.

    PubMed

    Saxena, N; Banerjee, S; Sengupta, K; Zoubine, M N; Banerjee, S K

    2001-12-01

    The transcriptional alterations of specific gene(s) are actively associated with the development of different cancers including breast. The preceding studies of different laboratories documented at least 40 genes that may contribute directly to the genesis of cancer. Using differential display, RT-PCR and DNA sequencing analyses in normal human mammary epithelial cells (HMEC) and various breast tumor cell lines including MCF-7, ZR-75, T-47D and SKBR2, we demonstrated that WISP-1 and WISP-2 genes are differentially transcribed in these cells. WISP-2 mRNA transcription was identified in all 4 tumor derived cell lines, but the mRNA expression was undetected or minimally detected in normal breast epithelial cells. WISP-1 mRNA expression was identified in normal and transformed cell lines. However, the level of expression was higher in different breast tumor cell lines as compared to HMEC. The mRNA expression profiles of WISP genes in normal breast epithelial cells and breast tumor derived cell lines indicated a strong possibility of the involvement of WISP-signaling in the development of human breast tumors, and can be utilized as genetic markers of this disease.

  15. Analysis of differential protein expression in normal and neoplastic human breast epithelial cell lines

    SciTech Connect

    Williams, K.; Chubb, C.; Huberman, E.; Giometti, C.S.

    1997-07-01

    High resolution two dimensional get electrophoresis (2DE) and database analysis was used to establish protein expression patterns for cultured normal human mammary epithelial cells and thirteen breast cancer cell lines. The Human Breast Epithelial Cell database contains the 2DE protein patterns, including relative protein abundances, for each cell line, plus a composite pattern that contains all the common and specifically expressed proteins from all the cell lines. Significant differences in protein expression, both qualitative and quantitative, were observed not only between normal cells and tumor cells, but also among the tumor cell lines. Eight percent of the consistently detected proteins were found in significantly (P < 0.001) variable levels among the cell lines. Using a combination of immunostaining, comigration with purified protein, subcellular fractionation, and amino-terminal protein sequencing, we identified a subset of the differentially expressed proteins. These identified proteins include the cytoskeletal proteins actin, tubulin, vimentin, and cytokeratins. The cell lines can be classified into four distinct groups based on their intermediate filament protein profile. We also identified heat shock proteins; hsp27, hsp60, and hsp70 varied in abundance and in some cases in the relative phosphorylation levels among the cell lines. Finally, we identified IMP dehydrogenase in each of the cell lines, and found the levels of this enzyme in the tumor cell lines elevated 2- to 20-fold relative to the levels in normal cells.

  16. Immunohistochemical distribution of type IV collagenase in normal, benign, and malignant breast tissue.

    PubMed Central

    Monteagudo, C.; Merino, M. J.; San-Juan, J.; Liotta, L. A.; Stetler-Stevenson, W. G.

    1990-01-01

    Production of type IV collagenase by tumor cells has been linked to their metastatic potential in several experimental models. A possible role for this enzyme in basement membrane type IV collagen turnover has also been suggested. Two recently developed affinity-purified, monospecific antibodies directed against the amino terminus (H1), or an internal active site domain (metal binding region [MBR]) of human type IV collagenase, were employed in the avidin-biotin-immunoperoxidase technique in formalin-fixed, paraffin-embedded breast tissue samples from 55 patients. Intense cytoplasmic immunostaining of myoepithelial cells was found in normal and hyperplastic tissue, and discontinuous staining was noted in intraductal carcinomas. Luminal epithelial cells were negative or weakly positive in large- or medium-sized ducts but reacted frequently in normal terminal ducts and hyperplastic lesions. Epithelial cells in intraductal carcinomas exhibited immunoreactivity in 20 of 23 cases. Invasive carcinomas were positive in 36 of 40 cases, and metastatic cells in lymph nodes stained in 10 of 12 cases. These results support a role for type IV collagenase in the basement membrane remodeling of normal breast. Our findings suggest that myoepithelial cells play a pivotal role in this enzymatic activity. The high percentage of positive cells in invasive carcinomas and the strong immunoreactivity of lymph node metastases support the role of the enzyme in tumor invasion and metastasis and suggest that tumor cells are the essential source of the enzyme in these processes. Images Figure 1 Figure 2 Figure 3 PMID:2156430

  17. CDDO-Me Protects Normal Lung and Breast Epithelial Cells but Not Cancer Cells from Radiation

    PubMed Central

    El-Ashmawy, Mariam; Delgado, Oliver; Cardentey, Agnelio; Wright, Woodring E.; Shay, Jerry W.

    2014-01-01

    Although radiation therapy is commonly used for treatment for many human diseases including cancer, ionizing radiation produces reactive oxygen species that can damage both cancer and healthy cells. Synthetic triterpenoids, including CDDO-Me, act as anti-inflammatory and antioxidant modulators primarily by inducing the transcription factor Nrf2 to activate downstream genes containing antioxidant response elements (AREs). In the present series of experiments, we determined if CDDO-Me can be used as a radioprotector in normal non-cancerous human lung and breast epithelial cells, in comparison to lung and breast cancer cell lines. A panel of normal non-cancerous, partially cancer progressed, and cancer cell lines from both lung and breast tissue was exposed to gamma radiation with and without pre-treatment with CDDO-Me. CDDO-Me was an effective radioprotector when given ∼18 hours before radiation in epithelial cells (average dose modifying factor (DMF) = 1.3), and Nrf2 function was necessary for CDDO-Me to exert these radioprotective effects. CDDO-Me did not protect cancer lines tested from radiation-induced cytotoxicity, nor did it protect experimentally transformed human bronchial epithelial cells (HBECs) with progressive oncogenic manipulations. CDDO-Me also protected human lymphocytes against radiation-induced DNA damage. A therapeutic window exists in which CDDO-Me protects normal cells from radiation by activating the Nrf2 pathway, but does not protect experimentally transformed or cancer cell lines. This suggests that use of this oral available, non-toxic class of drug can protect non-cancerous healthy cells during radiotherapy, resulting in better outcomes and less toxicity for patients. PMID:25536195

  18. CDDO-Me protects normal lung and breast epithelial cells but not cancer cells from radiation.

    PubMed

    El-Ashmawy, Mariam; Delgado, Oliver; Cardentey, Agnelio; Wright, Woodring E; Shay, Jerry W

    2014-01-01

    Although radiation therapy is commonly used for treatment for many human diseases including cancer, ionizing radiation produces reactive oxygen species that can damage both cancer and healthy cells. Synthetic triterpenoids, including CDDO-Me, act as anti-inflammatory and antioxidant modulators primarily by inducing the transcription factor Nrf2 to activate downstream genes containing antioxidant response elements (AREs). In the present series of experiments, we determined if CDDO-Me can be used as a radioprotector in normal non-cancerous human lung and breast epithelial cells, in comparison to lung and breast cancer cell lines. A panel of normal non-cancerous, partially cancer progressed, and cancer cell lines from both lung and breast tissue was exposed to gamma radiation with and without pre-treatment with CDDO-Me. CDDO-Me was an effective radioprotector when given ∼18 hours before radiation in epithelial cells (average dose modifying factor (DMF) = 1.3), and Nrf2 function was necessary for CDDO-Me to exert these radioprotective effects. CDDO-Me did not protect cancer lines tested from radiation-induced cytotoxicity, nor did it protect experimentally transformed human bronchial epithelial cells (HBECs) with progressive oncogenic manipulations. CDDO-Me also protected human lymphocytes against radiation-induced DNA damage. A therapeutic window exists in which CDDO-Me protects normal cells from radiation by activating the Nrf2 pathway, but does not protect experimentally transformed or cancer cell lines. This suggests that use of this oral available, non-toxic class of drug can protect non-cancerous healthy cells during radiotherapy, resulting in better outcomes and less toxicity for patients.

  19. TFF3 is a normal breast epithelial protein and is associated with differentiated phenotype in early breast cancer but predisposes to invasion and metastasis in advanced disease.

    PubMed

    Ahmed, Ahmed R H; Griffiths, Andrew B; Tilby, Michael T; Westley, Bruce R; May, Felicity E B

    2012-03-01

    The trefoil protein TFF3 stimulates invasion and angiogenesis in vitro. To determine whether it has a role in breast tumor metastasis and angiogenesis, its levels were measured by immunohistochemistry in breast tissue with a specific monoclonal antibody raised against human TFF3. TFF3 is expressed in normal breast lobules and ducts, at higher levels in areas of fibrocystic change and papillomas, in all benign breast disease lesions, and in 89% of in situ and in 83% of invasive carcinomas. In well-differentiated tumor cells, TFF3 is concentrated at the luminal edge, whereas in poorly differentiated cells polarity is inverted and expression is directed toward the stroma. Expression was high in well-differentiated tumors and was associated significantly with low histological grade and with estrogen and progesterone receptor expression, accordant with induction of TFF3 mRNA by estrogen in breast cancer cells. Paradoxically, TFF3 expression was associated with muscle, neural, and lymphovascular invasion and the presence and number of involved lymph nodes, and it was an independent predictive marker of lymphovascular invasion and lymph node involvement. Consistent with an angiogenic function, TFF3 expression correlated strongly with microvessel density evaluated with CD31 and CD34. In conclusion, TFF3 is expressed in both the normal and diseased breast. Although associated with features of good prognosis, its profile of expression in invasive cancer is consistent with a role in breast tumor progression and tumor cell dissemination.

  20. Proapoptotic CD95L levels in normal human serum and sera of breast cancer patients.

    PubMed

    Olimón-Andalón, Vicente; Aguilar-Lemarroy, Adriana; Ratkovich-González, Sarah; Uribe-López, Aida; Mariscal-Ramírez, Ignacio; Delgadillo-Cristerna, Raúl; Ortiz-Lazareno, Pablo; Hernández-Flores, Georgina; de Celis, Ruth; Bravo-Cuellar, Alejandro; Jave-Suárez, Luis F

    2015-05-01

    The CD95 pathway is a critical apoptotic pathway used by immune cells to avoid cancer development. CD95 ligand (CD95L) is found in several forms, as a cell membrane-associated form, a soluble metalloprotease-cleaved form, and a soluble but membrane-bound CD95L released on cell-derived exosomes. In this study, we used a cell-based assay to evaluate the activity of proapoptotic CD95L in sera from healthy individuals and breast cancer patients. We confirmed that our cell-based assay using Jurkat cells was sensitive to the presence of proapoptotic CD95L in serum, and apoptosis induction by mechanisms other than CD95 was discriminated using apoptosis-resistant Jurkat subclones. Our results indicated a proapoptotic potential of normal serum that involved CD95L. Sera from breast cancer patients exhibited significantly decreased apoptosis induction, due to increased CD95 receptor levels compared with healthy women. Apoptotic potential tended to decrease as the Breast Imaging Reporting and Data System grade increased, and we observed restoration of proapoptotic potential after tumor removal. The CD95L in serum responsible for apoptotic induction was associated with high-molecular-weight particles, perhaps with exosomes. The sera of healthy individuals generally contain a proapoptotic environment, and this property is mainly maintained by the presence of CD95L. Furthermore, measurement of CD95L-mediated apoptosis induction by sera could be a useful parameter to be evaluated during cancer development and therapeutic response.

  1. The role of the basal stem cell of the human breast in normal development and cancer

    PubMed Central

    Russo, Jose; Russo, Irma H.

    2011-01-01

    MCF-10F a spontaneously immortalized ERα negative human breast epithelial cell line derived from breast tissues containing Lobules type 1, is able to form normal ductal structures in a tridimensional collagen matrix system. MCF-10F cells that are Estrogen-transformed [trMCF cells] progressively express phenotypes of in vitro cell transformation, including colony formation in agar methocel, and loss of the ductulogenic capacity. Further selection of these trMCF cells for invasiveness in a Matrigel invasion system identified cells [bcMCF] that formed tumors in severe combined immunodeficient [SCID] mice. The cell lines derived from those tumors [caMCF] were poorly differentiated ERα, PR and ERBB2 negative adenocarcinomas. These characteristics are similar to the human basal cell-like carcinomas. This in vitro in vivo model demonstrates the importance of the basal cell type as a stem cell that reconstitute the branching pattern of the breast and that is also target of a carcinogenic insult leading to transformation and cancer. PMID:21901623

  2. Breast Cancer Stem Cells Transition between Epithelial and Mesenchymal States Reflective of their Normal Counterparts

    PubMed Central

    Liu, Suling; Cong, Yang; Wang, Dong; Sun, Yu; Deng, Lu; Liu, Yajing; Martin-Trevino, Rachel; Shang, Li; McDermott, Sean P.; Landis, Melissa D.; Hong, Suhyung; Adams, April; D’Angelo, Rosemarie; Ginestier, Christophe; Charafe-Jauffret, Emmanuelle; Clouthier, Shawn G.; Birnbaum, Daniel; Wong, Stephen T.; Zhan, Ming; Chang, Jenny C.; Wicha, Max S.

    2013-01-01

    Summary Previous studies have suggested that breast cancer stem cells (BCSCs) mediate metastasis, are resistant to radiation and chemotherapy, and contribute to relapse. Although several BCSC markers have been described, it is unclear whether these markers identify the same or independent BCSCs. Here, we show that BCSCs exist in distinct mesenchymal-like (epithelial-mesenchymal transition [EMT]) and epithelial-like (mesenchymal-epithelial transition [MET]) states. Mesenchymal-like BCSCs characterized as CD24−CD44+ are primarily quiescent and localized at the tumor invasive front, whereas epithelial-like BCSCs express aldehyde dehydrogenase (ALDH), are proliferative, and are located more centrally. The gene-expression profiles of mesenchymal-like and epithelial-like BCSCs are remarkably similar across different molecular subtypes of breast cancer, and resemble those of distinct basal and luminal stem cells found in the normal breast. We propose that the plasticity of BCSCs that allows them to transition between EMT- and MET-like states endows these cells with the capacity for tissue invasion, dissemination, and growth at metastatic sites. PMID:24511467

  3. DNA replication licensing and cell cycle kinetics of normal and neoplastic breast

    PubMed Central

    Shetty, A; Loddo, M; Fanshawe, T; Prevost, A T; Sainsbury, R; Williams, G H; Stoeber, K

    2005-01-01

    Mcm2–7 (MCM) proteins are part of the origin licensing machinery that regulates initiation of DNA replication. Geminin is a licensing repressor and prevents reinitiation of DNA replication during S–G2–M phase by blocking reloading of Mcm2–7 at replication origins. Here, we have analysed these replication licensing factors (RLFs) to determine whether the pathway becomes deregulated during mammary carcinogenesis, and have assessed their potential value as prognostic markers. Protein expression profiles were generated for Ki67, Mcm2, geminin, HER-2, ER and PR in a series of reduction mammoplasty (n=18) and breast cancer specimens (n=120), and compared to clinicopathological parameters. A large proportion of epithelial cells of the terminal duct lobular unit reside in a primed ‘replication licensed' but not proliferating state. This state is characterised by Mcm2 expression and absence of Ki67 and the S/G2/M marker geminin. In breast cancers, increasing tumour grade is associated with increased Ki67, Mcm2 and geminin expression. The Mcm2/Ki67 ratio decreases through the grades, indicating a shift from a predominantly licensed state to an actively proliferating state. This shift is associated with an increase in the geminin/Ki67 ratio, signifying a shortening of G1 phase in breast cancer cells. Ki67, Mcm2 and the Mcm2/Ki67 ratio are statistically significantly associated with the Nottingham Prognostic Index (NPI), but geminin and the geminin/Ki67 ratio are not. Ki67, Mcm2 and Mcm2/Ki67 are highly correlated with one another, with Mcm2 being the single most important predictor of NPI score (P<0.001). However, only 12% of variation in NPI is explained by Mcm2, as the labelling index for this marker is approaching 100% for many of the high-grade tumours. The origin licensing phenotypes of normal breast and breast cancers therefore relate to their cellular differentiation status, and high-level MCM expression in more poorly differentiated tumours severely

  4. The biology of progesterone receptor in the normal mammary gland and in breast cancer.

    PubMed

    Obr, Alison E; Edwards, Dean P

    2012-06-24

    This paper reviews work on progesterone and the progesterone receptor (PR) in the mouse mammary gland that has been used extensively as an experimental model. Studies have led to the concept that progesterone controls proliferation and morphogenesis of the luminal epithelium in a tightly orchestrated manner at distinct stages of development by paracrine signaling pathways, including receptor activator of nuclear factor κB ligand (RANKL) as a major paracrine factor. Progesterone also drives expansion of stem cells by paracrine signals to generate progenitors required for alveologenesis. During mid-to-late pregnancy, progesterone has another role to suppress secretory activation until parturition mediated in part by crosstalk between PR and prolactin/Stat5 signaling to inhibit induction of milk protein gene expression, and by inhibiting tight junction closure. In models of hormone-dependent mouse mammary tumors, the progesterone/PR signaling axis enhances pre-neoplastic progression by a switch from a paracrine to an autocrine mode of proliferation and dysregulation of the RANKL signaling pathway. Limited experiments with normal human breast show that progesterone/PR signaling also stimulates epithelial cell proliferation by a paracrine mechanism; however, the signaling pathways and whether RANKL is a major mediator remains unknown. Work with human breast cancer cell lines, patient tumor samples and clinical studies indicates that progesterone is a risk factor for breast cancer and that alteration in progesterone/PR signaling pathways contributes to early stage human breast cancer progression. However, loss of PR expression in primary tumors is associated with a less differentiated more invasive phenotype and worse prognosis, suggesting that PR may limit later stages of tumor progression.

  5. PTK6/BRK is expressed in the normal mammary gland and activated at the plasma membrane in breast tumors.

    PubMed

    Peng, Maoyu; Emmadi, Rajyasree; Wang, Zebin; Wiley, Elizabeth L; Gann, Peter H; Khan, Seema A; Banerji, Nilanjana; McDonald, William; Asztalos, Szilard; Pham, Thao N D; Tonetti, Debra A; Tyner, Angela L

    2014-08-15

    Protein Tyrosine kinase 6 (PTK6/BRK) is overexpressed in the majority of human breast tumors and breast tumor cell lines. It is also expressed in normal epithelial linings of the gastrointestinal tract, skin, and prostate. To date, expression of PTK6 has not been extensively examined in the normal human mammary gland. We detected PTK6 mRNA and protein expression in the immortalized normal MCF-10A human mammary gland epithelial cell line, and examined PTK6 expression and activation in a normal human breast tissue microarray, as well as in human breast tumors. Phosphorylation of tyrosine residue 342 in the PTK6 activation loop corresponds with its activation. Similar to findings in the prostate, we detect nuclear and cytoplasmic PTK6 in normal mammary gland epithelial cells, but no phosphorylation of tyrosine residue 342. However, in human breast tumors, striking PTK6 expression and phosphorylation of tyrosine 342 is observed at the plasma membrane. PTK6 is expressed in the normal human mammary gland, but does not appear to be active and may have kinase-independent functions that are distinct from its cancer promoting activities at the membrane. Understanding consequences of PTK6 activation at the plasma membrane may have implications for developing novel targeted therapies against this kinase.

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

    PubMed

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

    2012-01-01

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

  7. Fingerprinting Breast Cancer vs. Normal Mammary Cells by Mass Spectrometric Analysis of Volatiles

    NASA Astrophysics Data System (ADS)

    He, Jingjing; Sinues, Pablo Martinez-Lozano; Hollmén, Maija; Li, Xue; Detmar, Michael; Zenobi, Renato

    2014-06-01

    There is increasing interest in the development of noninvasive diagnostic methods for early cancer detection, to improve the survival rate and quality of life of cancer patients. Identification of volatile metabolic compounds may provide an approach for noninvasive early diagnosis of malignant diseases. Here we analyzed the volatile metabolic signature of human breast cancer cell lines versus normal human mammary cells. Volatile compounds in the headspace of conditioned culture medium were directly fingerprinted by secondary electrospray ionization-mass spectrometry. The mass spectra were subsequently treated statistically to identify discriminating features between normal vs. cancerous cell types. We were able to classify different samples by using feature selection followed by principal component analysis (PCA). Additionally, high-resolution mass spectrometry allowed us to propose their chemical structures for some of the most discriminating molecules. We conclude that cancerous cells can release a characteristic odor whose constituents may be used as disease markers.

  8. Surface modification of microparticles causes differential uptake responses in normal and tumoral human breast epithelial cells

    NASA Astrophysics Data System (ADS)

    Patiño, Tania; Soriano, Jorge; Barrios, Lleonard; Ibáñez, Elena; Nogués, Carme

    2015-06-01

    The use of micro- and nanodevices as multifunctional systems for biomedical applications has experienced an exponential growth during the past decades. Although a large number of studies have focused on the design and fabrication of new micro- and nanosystems capable of developing multiple functions, a deeper understanding of their interaction with cells is required. In the present study, we evaluated the effect of different microparticle surfaces on their interaction with normal and tumoral human breast epithelial cell lines. For this, AlexaFluor488 IgG functionalized polystyrene microparticles (3 μm) were coated with Polyethyleneimine (PEI) at two different molecular weights, 25 and 750 kDa. The effect of microparticle surface properties on cytotoxicity, cellular uptake and endocytic pathways were assessed for both normal and tumoral cell lines. Results showed a differential response between the two cell lines regarding uptake efficiency and mechanisms of endocytosis, highlighting the potential role of microparticle surface tunning for specific cell targeting.

  9. Measurement of pressure-displacement kinetics of hemoglobin in normal breast tissue with near-infrared spectral imaging

    SciTech Connect

    Jiang, Shudong; Pogue, Brian W.; Laughney, Ashley M.; Kogel, Christine A.; Paulsen, Keith D

    2009-04-01

    Applying localized external displacement to the breast surface can change the interstitial fluid pressure such that regional transient microvascular changes occur in oxygenation and vascular volume. Imaging these dynamic responses over time, while different pressures are applied, could provide selective temporal contrast for cancer relative to the surrounding normal breast. In order to investigate this possibility in normal breast tissue, a near-infrared spectral tomography system was developed that can simultaneously acquire data at three wavelengths with a 15 s time resolution per scan. The system was tested first with heterogeneous blood phantoms. Changes in regional blood concentrations were found to be linearly related to recovered mean hemoglobin concentration (HbT) values (R{sup 2}=0.9). In a series of volunteer breast imaging exams, data from 17 asymptomatic subjects were acquired under increasing and decreasing breast compression. Calculations show that a 10 mm displacement applied to the breast results in surface pressures in the range of 0-55 kPa depending on breast density. The recovered human data indicate that HbT was reduced under compression and the normalized change was significantly correlated to the applied pressure with a p value of 0.005. The maximum HbT decreases in breast tissue were associated with body mass index (BMI), which is a surrogate indicator of breast density. No statistically valid correlations were found between the applied pressure and the changes in tissue oxygen saturation (StO2) or water percentage (H2O) across the range of BMI values studied.

  10. Adipocyte differentiation influences the proliferation and migration of normal and tumoral breast epithelial cells.

    PubMed

    Creydt, Virginia Pistone; Sacca, Paula Alejandra; Tesone, Amelia Julieta; Vidal, Luciano; Calvo, Juan Carlos

    2010-01-01

    Stromal tissue regulates the development and differentiation of breast epithelial cells, with adipocytes being the main stromal cell type. The aim of the present study was to evaluate the effect of adipocyte differentiation on proliferation and migration, as well as to assess the activity of heparanase and metalloproteinase-9 (MMP-9), in normal (NMuMG) and tumoral (LM3) murine breast epithelial cells. NMuMG and LM3 cells were grown on irradiated 3T3-L1 cells (stromal support, SS) at various degrees of differentiation [preadipocytes (preA), poorly differentiated adipocytes (pDA) and mature adipocytes (MA)] and/or were incubated in the presence of conditioned medium (CM) derived from each of these three types of differentiated cells. Cells grown on a plastic support or in fresh medium served as the controls. Cell proliferation was measured with a commercial colorimetric kit, and the motility of the epithelial cells was evaluated by means of a wound-healing assay. Heparanase activity was assessed by quantifying heparin degradation, and the expression of MMP-9 was determined using Western blotting. The results indicate that cell proliferation was increased after 24 and 48 h in the NMuMG and LM3 cells grown on preA, pDA and MA SS. In the NMuMG cells cultured on SS in the presence of all three types of CM, proliferation was enhanced. LM3 cell migration was increased in the presence of all three types of CM and in cells grown on preA SS. Heparanase activity was increased in the NMuMG cells incubated with all three types of CM, and in the LM3 cells incubated with the CM from pDA and MA. Both the NMuMG and LM3 cell lines presented basal expression of MMP-9; however, a significant increase in MMP-9 expression was observed in the LM3 cells incubated with each of the three types of CM. In conclusion, adipocyte differentiation influences normal and tumoral breast epithelial cell proliferation and migration. Heparanase and MMP-9 appear to be involved in this regulation. The

  11. Quantitative changes of collagen in human normal breast tissue and invasive ductal carcinoma using nonlinear optical microscopy

    NASA Astrophysics Data System (ADS)

    Li, Weiqiang; Wu, Yan; Lian, Yuane; Fu, Fangmeng; Wang, Chuan; Zhuo, Shuangmu; Chen, Jianxin

    2014-11-01

    Multiphoton microscopy (MPM) imaging of collagen plays a key role in noninvasive diagnosis of human tissue. During the experiment, we observed an interesting phenomenon which two-photon excited fluorescence (TPEF) signal of collagen in human invasive ductal carcinoma of breast tissue becomes much weaker than the normal breast tissue, but the second harmonic generation (SHG) signal of collagen does not get an obvious change . In order to explain the phenomena,this paper emphasizes on the intensity of TPEF and SHG signal from collagen in human invasive ductal carcinoma of breast tissues and normal breast tissue. Further, we respectively obtain the intensity spectral information from collagen in the above two tissues with all parameter unaltered. Our quantitative results show that the intensity of TPEF from collagen in human invasive ductal carcinoma of breast tissue is much lower than the intensity of TPEF from collagen in normal breast tissue. According to the theoretic analysis, it was concluded that the intensity of TPEF declined due to the reduction of the quantum yield when the collagen was intruded by cancer cells. However, the invasion of cancer cells has no effect on decisive factor of SHG. Our theoretical analysis brings more detailed information about intensity of SHG and TPEF from collagen in the above two tissues.

  12. The myoepithelial cell: its role in normal mammary glands and breast cancer.

    PubMed

    Sopel, M

    2010-02-01

    Mammary gland epithelium is composed of an inner layer of secretory cells (luminal) and an outer layer of myoepithelial cells (MEC) bordering the basal lamina which separates the epithelial layer from the extracellular matrix. Mature MECs morphologically resemble smooth muscle cells; however, they exhibit features typical for epithelial cells, such as the presence of specific cytokeratin filaments. During lactation, secretory cells synthesize milk components, which are collected in alveoli and duct lumen, and transported to the nipple as a result of MEC contraction. Although the induction of MEC contraction results from oxytocin action, also other, still unknown auto/paracrine mechanisms participate in the regulation of this process. As well as milk ejection, MECs are involved in mammary gland morphogenesis in all developmental stages, modulating proliferation and differentiation of luminal cells. They take part in the formation of extracellular matrix, synthesizing its components and secreting proteinases and their inhibitors. In addition, MECs are regarded as natural cancer suppressors, stabilizing the normal structure of the mammary gland, they secrete suppressor proteins (e.g. maspin) limiting cancer growth, invasiveness, and neoangiogenesis. The majority of malignant breast cancers are derived from luminal cells, whereas neoplasms of MEC origin are the most seldom and usually benign form of breast tumours. MECs are markedly resistant to malignant transformation and they are able to suppress the transformation of neighboring luminal cells. Therefore, a deeper insight into the role of MECs in the physiology and pathology of mammary glands would allow a better understanding of cancerogenesis mechanisms and possible application of specific MEC markers in the diagnosis and therapy of breast cancer.

  13. Signatures of post-zygotic structural genetic aberrations in the cells of histologically normal breast tissue that can predispose to sporadic breast cancer

    PubMed Central

    Forsberg, Lars A.; Rasi, Chiara; Pekar, Gyula; Davies, Hanna; Piotrowski, Arkadiusz; Absher, Devin; Razzaghian, Hamid Reza; Ambicka, Aleksandra; Halaszka, Krzysztof; Przewoźnik, Marcin; Kruczak, Anna; Mandava, Geeta; Pasupulati, Saichand; Hacker, Julia; Prakash, K. Reddy; Dasari, Ravi Chandra; Lau, Joey; Penagos-Tafurt, Nelly; Olofsson, Helena M.; Hallberg, Gunilla; Skotnicki, Piotr; Mituś, Jerzy; Skokowski, Jaroslaw; Jankowski, Michal; Śrutek, Ewa; Zegarski, Wojciech; Tiensuu Janson, Eva; Ryś, Janusz; Tot, Tibor; Dumanski, Jan P.

    2015-01-01

    Sporadic breast cancer (SBC) is a common disease without robust means of early risk prediction in the population. We studied 282 females with SBC, focusing on copy number aberrations in cancer-free breast tissue (uninvolved margin, UM) outside the primary tumor (PT). In total, 1162 UMs (1–14 per breast) were studied. Comparative analysis between UM(s), PT(s), and blood/skin from the same patient as a control is the core of the study design. We identified 108 patients with at least one aberrant UM, representing 38.3% of cases. Gains in gene copy number were the principal type of mutations in microscopically normal breast cells, suggesting that oncogenic activation of genes via increased gene copy number is a predominant mechanism for initiation of SBC pathogenesis. The gain of ERBB2, with overexpression of HER2 protein, was the most common aberration in normal cells. Five additional growth factor receptor genes (EGFR, FGFR1, IGF1R, LIFR, and NGFR) also showed recurrent gains, and these were occasionally present in combination with the gain of ERBB2. All the aberrations found in the normal breast cells were previously described in cancer literature, suggesting their causative, driving role in pathogenesis of SBC. We demonstrate that analysis of normal cells from cancer patients leads to identification of signatures that may increase risk of SBC and our results could influence the choice of surgical intervention to remove all predisposing cells. Early detection of copy number gains suggesting a predisposition toward cancer development, long before detectable tumors are formed, is a key to the anticipated shift into a preventive paradigm of personalized medicine for breast cancer. PMID:26430163

  14. Signatures of post-zygotic structural genetic aberrations in the cells of histologically normal breast tissue that can predispose to sporadic breast cancer.

    PubMed

    Forsberg, Lars A; Rasi, Chiara; Pekar, Gyula; Davies, Hanna; Piotrowski, Arkadiusz; Absher, Devin; Razzaghian, Hamid Reza; Ambicka, Aleksandra; Halaszka, Krzysztof; Przewoźnik, Marcin; Kruczak, Anna; Mandava, Geeta; Pasupulati, Saichand; Hacker, Julia; Prakash, K Reddy; Dasari, Ravi Chandra; Lau, Joey; Penagos-Tafurt, Nelly; Olofsson, Helena M; Hallberg, Gunilla; Skotnicki, Piotr; Mituś, Jerzy; Skokowski, Jaroslaw; Jankowski, Michal; Śrutek, Ewa; Zegarski, Wojciech; Tiensuu Janson, Eva; Ryś, Janusz; Tot, Tibor; Dumanski, Jan P

    2015-10-01

    Sporadic breast cancer (SBC) is a common disease without robust means of early risk prediction in the population. We studied 282 females with SBC, focusing on copy number aberrations in cancer-free breast tissue (uninvolved margin, UM) outside the primary tumor (PT). In total, 1162 UMs (1-14 per breast) were studied. Comparative analysis between UM(s), PT(s), and blood/skin from the same patient as a control is the core of the study design. We identified 108 patients with at least one aberrant UM, representing 38.3% of cases. Gains in gene copy number were the principal type of mutations in microscopically normal breast cells, suggesting that oncogenic activation of genes via increased gene copy number is a predominant mechanism for initiation of SBC pathogenesis. The gain of ERBB2, with overexpression of HER2 protein, was the most common aberration in normal cells. Five additional growth factor receptor genes (EGFR, FGFR1, IGF1R, LIFR, and NGFR) also showed recurrent gains, and these were occasionally present in combination with the gain of ERBB2. All the aberrations found in the normal breast cells were previously described in cancer literature, suggesting their causative, driving role in pathogenesis of SBC. We demonstrate that analysis of normal cells from cancer patients leads to identification of signatures that may increase risk of SBC and our results could influence the choice of surgical intervention to remove all predisposing cells. Early detection of copy number gains suggesting a predisposition toward cancer development, long before detectable tumors are formed, is a key to the anticipated shift into a preventive paradigm of personalized medicine for breast cancer.

  15. Attenuated total reflectance Fourier transform infrared spectroscopy method to differentiate between normal and cancerous breast cells.

    PubMed

    Lane, Randy; See, Seong S

    2012-09-01

    Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) is used to find the structural differences between cancerous breast cells (MCF-7 line) and normal breast cells (MCF-12F line). Gold nanoparticles were prepared and the hydrodynamic diameter of the gold nanoparticles found to be 38.45 nm. The Gold nanoparticles were exposed to both MCF-7 and MCF-12F cells from lower to higher concentrations. Spectroscopic studies founds nanoparticles were within the cells, and increasing the nanoparticles concentration inside the cells also resulted in sharper IR peaks as a result of localized surface Plasmon resonance. Asymmetric and symmetric stretching and bending vibrations between phosphate, COO-, CH2 groups were found to give negative shifts in wavenumbers and a decrease in peak intensities when going from noncancerous to cancerous cells. Cellular proteins produced peak assignments at the 1542 and 1644 cm(-1) wavenumbers which were attributed to the amide I and amide II bands of the polypeptide bond of proteins. Significant changes were found in the peak intensities between the cell lines in the spectrum range from 2854-2956 cm(-1). Results show that the concentration range of gold nanoparticles used in this research showed no significant changes in cell viability in either cell line. Therefore, we believe ATR-FTIR and gold nanotechnology can be at the forefront of cancer diagnosis for some time to come.

  16. Pluripotency Genes and Their Functions in the Normal and Aberrant Breast and Brain.

    PubMed

    Seymour, Tracy; Twigger, Alecia-Jane; Kakulas, Foteini

    2015-01-01

    Pluripotent stem cells (PSCs) attracted considerable interest with the successful isolation of embryonic stem cells (ESCs) from the inner cell mass of murine, primate and human embryos. Whilst it was initially thought that the only PSCs were ESCs, in more recent years cells with similar properties have been isolated from organs of the adult, including the breast and brain. Adult PSCs in these organs have been suggested to be remnants of embryonic development that facilitate normal tissue homeostasis during repair and regeneration. They share certain characteristics with ESCs, such as an inherent capacity to self-renew and differentiate into cells of the three germ layers, properties that are regulated by master pluripotency transcription factors (TFs) OCT4 (octamer-binding transcription factor 4), SOX2 (sex determining region Y-box 2), and homeobox protein NANOG. Aberrant expression of these TFs can be oncogenic resulting in heterogeneous tumours fueled by cancer stem cells (CSC), which are resistant to conventional treatments and are associated with tumour recurrence post-treatment. Further to enriching our understanding of the role of pluripotency TFs in normal tissue function, research now aims to develop optimized isolation and propagation methods for normal adult PSCs and CSCs for the purposes of regenerative medicine, developmental biology, and disease modeling aimed at targeted personalised cancer therapies. PMID:26580604

  17. Pluripotency Genes and Their Functions in the Normal and Aberrant Breast and Brain.

    PubMed

    Seymour, Tracy; Twigger, Alecia-Jane; Kakulas, Foteini

    2015-11-13

    Pluripotent stem cells (PSCs) attracted considerable interest with the successful isolation of embryonic stem cells (ESCs) from the inner cell mass of murine, primate and human embryos. Whilst it was initially thought that the only PSCs were ESCs, in more recent years cells with similar properties have been isolated from organs of the adult, including the breast and brain. Adult PSCs in these organs have been suggested to be remnants of embryonic development that facilitate normal tissue homeostasis during repair and regeneration. They share certain characteristics with ESCs, such as an inherent capacity to self-renew and differentiate into cells of the three germ layers, properties that are regulated by master pluripotency transcription factors (TFs) OCT4 (octamer-binding transcription factor 4), SOX2 (sex determining region Y-box 2), and homeobox protein NANOG. Aberrant expression of these TFs can be oncogenic resulting in heterogeneous tumours fueled by cancer stem cells (CSC), which are resistant to conventional treatments and are associated with tumour recurrence post-treatment. Further to enriching our understanding of the role of pluripotency TFs in normal tissue function, research now aims to develop optimized isolation and propagation methods for normal adult PSCs and CSCs for the purposes of regenerative medicine, developmental biology, and disease modeling aimed at targeted personalised cancer therapies.

  18. Small breast lesion classification performance using the normalized axial-shear strain area feature.

    PubMed

    Thittai, Arun K; Yamal, Jose-Miguel; Ophir, Jonathan

    2013-03-01

    Breast cancers that are found and confirmed because they are causing symptoms tend to be larger and are more likely to have already spread to the lymph nodes and beyond. Thus, early detection and confirmation are of paramount importance. The normalized axial-shear strain area (NASSA) feature from the axial-shear strain elastogram (ASSE) has been shown to be a feature that can identify the boundary-bonding conditions that are indicative of the presence of cancer. Recently, we investigated and reported on the potential of the NASSA feature for breast lesion classification into fibroadenomas and cancers. In this article, we investigate the size distribution of the lesions that were part of the previous study and analyze classification performance specifically on small lesions (<10 mm diameter). A total of 33 biopsy-proven malignant tumors and 30 fibroadenomas were part of the study that involved three observers blinded to the Breast Imaging Reporting and Data System (BIRADS) ultrasound scores. The observers outlined the lesions on the sonograms and the lesion size (maximum circle-equivalent diameter in millimeters) was computed from this outline. The ASSE was automatically segmented and color-overlaid on the sonogram, and the NASSA feature from ASSE was computed semi-automatically. Receiver operating characteristic curves were then generated for the subset of cases involving small lesions. Box plots were produced for the two different lesion size groups, small and large, from a logistic regression classifier that was built previously. The results of our study show that approximately 38% and 22% of the fibroadenomas and cancers, respectively, were small. Furthermore, it was found that the NASSA feature resulted in a perfect classification of the small lesions, both in the training data and in the cross-validation. For lesions <10 mm the difference in fibroadenoma and cancer mean scores was 0.73 ± 0.13 (p < 0.001), whereas lesions >10 mm had a difference of 0.52 ± 0

  19. Elastic moduli of normal and pathological human breast tissues: an inversion-technique-based investigation of 169 samples

    NASA Astrophysics Data System (ADS)

    Samani, Abbas; Zubovits, Judit; Plewes, Donald

    2007-03-01

    Understanding and quantifying the mechanical properties of breast tissues has been a subject of interest for the past two decades. This has been motivated in part by interest in modelling soft tissue response for surgery planning and virtual-reality-based surgical training. Interpreting elastography images for diagnostic purposes also requires a sound understanding of normal and pathological tissue mechanical properties. Reliable data on tissue elastic properties are very limited and those which are available tend to be inconsistent, in part as a result of measurement methodology. We have developed specialized techniques to measure tissue elasticity of breast normal tissues and tumour specimens and applied them to 169 fresh ex vivo breast tissue samples including fat and fibroglandular tissue as well as a range of benign and malignant breast tumour types. Results show that, under small deformation conditions, the elastic modulus of normal breast fat and fibroglandular tissues are similar while fibroadenomas were approximately twice the stiffness. Fibrocystic disease and malignant tumours exhibited a 3-6-fold increased stiffness with high-grade invasive ductal carcinoma exhibiting up to a 13-fold increase in stiffness compared to fibrogalndular tissue. A statistical analysis showed that differences between the elastic modulus of the majority of those tissues were statistically significant. Implications for the specificity advantages of elastography are reviewed.

  20. A new normal?: Women's experiences of biographical disruption and liminality following treatment for early stage breast cancer.

    PubMed

    Trusson, Diane; Pilnick, Alison; Roy, Srila

    2016-02-01

    Increasing numbers of women are surviving breast cancer, but little is known about the long-term implications of having survived a life-threatening illness and living with embodied reminders of its potential to return. Twenty-four women aged between 42 and 80 (median = 51)who had been treated for early stage breast cancer in the UK between 6 months and 29 years previously, were recruited through local media and interviewed. Analysis of their narratives revealed challenges in the post-treatment period that were conceptualised as biographical disruption and liminality. Although no longer ill, an ongoing fear of recurrence combined with embodied changes prevented a return to 'normal' i.e. a pre-cancer state in terms of health status, identity and relationships. We argue that following the biographical disruption of breast cancer, a 'new normal' entails a continual renegotiation of identities, daily lives and futures as time passes and lives evolve. PMID:26802368

  1. An "elite hacker": breast tumors exploit the normal microenvironment program to instruct their progression and biological diversity.

    PubMed

    Boudreau, Aaron; van't Veer, Laura J; Bissell, Mina J

    2012-01-01

    The year 2011 marked the 40 year anniversary of Richard Nixon signing the National Cancer Act, thus declaring the beginning of the "War on Cancer" in the United States. Whereas we have made tremendous progress toward understanding the genetics of tumors in the past four decades, and in developing enabling technology to dissect the molecular underpinnings of cancer at unprecedented resolution, it is only recently that the important role of the stromal microenvironment has been studied in detail. Cancer is a tissue-specific disease, and it is becoming clear that much of what we know about breast cancer progression parallels the biology of the normal breast differentiation, of which there is still much to learn. In particular, the normal breast and breast tumors share molecular, cellular, systemic and microenvironmental influences necessary for their progression. It is therefore enticing to consider a tumor to be a "rogue hacker"--one who exploits the weaknesses of a normal program for personal benefit. Understanding normal mammary gland biology and its "security vulnerabilities" may thus leave us better equipped to target breast cancer. In this review, we will provide a brief overview of the heterotypic cellular and molecular interactions within the microenvironment of the developing mammary gland that are necessary for functional differentiation, provide evidence suggesting that similar biology--albeit imbalanced and exaggerated--is observed in breast cancer progression particularly during the transition from carcinoma in situ to invasive disease. Lastly we will present evidence suggesting that the multigene signatures currently used to model cancer heterogeneity and clinical outcome largely reflect signaling from a heterogeneous microenvironment-a recurring theme that could potentially be exploited therapeutically. PMID:22863741

  2. Normalization.

    ERIC Educational Resources Information Center

    Cuevas, Eduardo J.

    1997-01-01

    Discusses cornerstone of Montessori theory, normalization, which asserts that if a child is placed in an optimum prepared environment where inner impulses match external opportunities, the undeviated self emerges, a being totally in harmony with its surroundings. Makes distinctions regarding normalization, normalized, and normality, indicating how…

  3. A differential role for CXCR4 in the regulation of normal versus malignant breast stem cell activity.

    PubMed

    Ablett, Matthew P; O'Brien, Ciara S; Sims, Andrew H; Farnie, Gillian; Clarke, Robert B

    2014-02-15

    C-X-C chemokine receptor type 4 (CXCR4) is known to regulate lung, pancreatic and prostate cancer stem cells. In breast cancer, CXCR4 signalling has been reported to be a mediator of metastasis, and is linked to poor prognosis. However its role in normal and malignant breast stem cell function has not been investigated. Anoikis resistant (AR) cells were collected from immortalised (MCF10A, 226L) and malignant (MCF7, T47D, SKBR3) breast cell lines and assessed for stem cell enrichment versus unsorted cells. AR cells had significantly higher mammosphere forming efficiency (MFE) than unsorted cells. The AR normal cells demonstrated increased formation of 3D structures in Matrigel compared to unsorted cells. In vivo, SKBR3 and T47D AR cells had 7- and 130-fold enrichments for tumour formationrespectively, compared with unsorted cells. AR cells contained significantly elevated CXCR4 transcript and protein levels compared to unsorted cells. Importantly, CXCR4 mRNA was higher in stem cell-enriched CD44+/CD24- patient-derived breast cancer cells compared to non-enriched cells. CXCR4 stimulation by its ligand SDF-1 reduced MFE of the normal breast cells lines but increased the MFE in T47D and patient-derived breast cancer cells. CXCR4 inhibition by AMD3100 increased stem cell activity but reduced the self-renewal capacity of the malignant breast cell line T47D. CXCR4+ FACS sorted MCF7 cells demonstrated a significantly increased MFE compared with CXCR4- cells. This significant increase in MFE was further demonstrated in CXCR4 over-expressing MCF7 cells which also had an increase in self-renewal compared to parental cells. A greater reduction in self-renewal following CXCR4 inhibition in the CXCR4 over-expressing cells compared with parental cells was also observed. Our data establish for the first time that CXCR4 signalling has contrasting effects on normal and malignant breast stem cell activity. Here, we demonstrate that CXCR4 signalling specifically regulates breast

  4. A differential role for CXCR4 in the regulation of normal versus malignant breast stem cell activity

    PubMed Central

    Ablett, Matthew P.; O'Brien, Ciara S.; Sims, Andrew H.; Farnie, Gillian; Clarke, Robert B.

    2014-01-01

    C-X-C chemokine receptor type 4 (CXCR4) is known to regulate lung, pancreatic and prostate cancer stem cells. In breast cancer, CXCR4 signalling has been reported to be a mediator of metastasis, and is linked to poor prognosis. However its role in normal and malignant breast stem cell function has not been investigated. Anoikis resistant (AR) cells were collected from immortalised (MCF10A, 226L) and malignant (MCF7, T47D, SKBR3) breast cell lines and assessed for stem cell enrichment versus unsorted cells. AR cells had significantly higher mammosphere forming efficiency (MFE) than unsorted cells. The AR normal cells demonstrated increased formation of 3D structures in Matrigel compared to unsorted cells. In vivo, SKBR3 and T47D AR cells had 7- and 130-fold enrichments for tumour formation respectively, compared with unsorted cells. AR cells contained significantly elevated CXCR4 transcript and protein levels compared to unsorted cells. Importantly, CXCR4 mRNA was higher in stem cell-enriched CD44+ /CD24− - patient-derived breast cancer cells compared to non-enriched cells. CXCR4 stimulation by its ligand SDF-1 reduced MFE of the normal breast cells lines but increased the MFE in T47D and patient-derived breast cancer cells. CXCR4 inhibition by AMD3100 increased stem cell activity but reduced the self-renewal capacity of the malignant breast cell line T47D. CXCR4 + FACS sorted MCF7 cells demonstrated a significantly increased MFE compared with CXCR4- cells. This significant increase in MFE was further demonstrated in CXCR4 over-expressing MCF7 cells which also had an increase in self-renewal compared to parental cells. A greater reduction in self-renewal following CXCR4 inhibition in the CXCR4 over-expressing cells compared with parental cells was also observed. Our data establish for the first time that CXCR4 signalling has contrasting effects on normal and malignant breast stem cell activity. Here, we demonstrate that CXCR4 signalling specifically regulates

  5. Reliability of Quantitative Ultrasonic Assessment of Normal-Tissue Toxicity in Breast Cancer Radiotherapy

    SciTech Connect

    Yoshida, Emi J.; Chen Hao; Torres, Mylin; Andic, Fundagul; Liu Haoyang; Chen Zhengjia; Sun, Xiaoyan; Curran, Walter J.; Liu Tian

    2012-02-01

    Purpose: We have recently reported that ultrasound imaging, together with ultrasound tissue characterization (UTC), can provide quantitative assessment of radiation-induced normal-tissue toxicity. This study's purpose is to evaluate the reliability of our quantitative ultrasound technology in assessing acute and late normal-tissue toxicity in breast cancer radiotherapy. Method and Materials: Our ultrasound technique analyzes radiofrequency echo signals and provides quantitative measures of dermal, hypodermal, and glandular tissue toxicities. To facilitate easy clinical implementation, we further refined this technique by developing a semiautomatic ultrasound-based toxicity assessment tool (UBTAT). Seventy-two ultrasound studies of 26 patients (720 images) were analyzed. Images of 8 patients were evaluated for acute toxicity (<6 months postradiotherapy) and those of 18 patients were evaluated for late toxicity ({>=}6 months postradiotherapy). All patients were treated according to a standard radiotherapy protocol. To assess intraobserver reliability, one observer analyzed 720 images in UBTAT and then repeated the analysis 3 months later. To assess interobserver reliability, three observers (two radiation oncologists and one ultrasound expert) each analyzed 720 images in UBTAT. An intraclass correlation coefficient (ICC) was used to evaluate intra- and interobserver reliability. Ultrasound assessment and clinical evaluation were also compared. Results: Intraobserver ICC was 0.89 for dermal toxicity, 0.74 for hypodermal toxicity, and 0.96 for glandular tissue toxicity. Interobserver ICC was 0.78 for dermal toxicity, 0.74 for hypodermal toxicity, and 0.94 for glandular tissue toxicity. Statistical analysis found significant changes in dermal (p < 0.0001), hypodermal (p = 0.0027), and glandular tissue (p < 0.0001) assessments in the acute toxicity group. Ultrasound measurements correlated with clinical Radiation Therapy Oncology Group (RTOG) toxicity scores of patients

  6. Fibroblast radiosensitivity versus acute and late normal skin responses in patients treated for breast cancer

    SciTech Connect

    Brock, W.A.; Wike, J.; Tucker, S.L.

    1995-07-30

    To determine if the radiosensitivity of normal human skin fibroblasts, measured in early passage cultures, is significantly correlated with the degree of acute or late normal skin damage in patients treated for breast cancer with radiotherapy. To test assay reproducibility, SF2 values derived from paired biopsies of the same patient (12 cases) were compared. A reasonably good correlation (p = 0.075) was obtained for SF2s determined by high dose-rate irradiations with immediated plating, but not for delayed plating or low dose-rate treatments. The median coefficient of variation in the replicate SF2s after high dose-rate treatment and immediate plating was 13%, suggesting that the poor correlation in paired SF2 values is due to the magnitude of the uncertainty in SF2 relative to the overall spread in SF2 values between patients (CV = 28%). Individual SF2 values and averaged values from patients with data from two biopsies were compared with the acute and late clinical reactions. A significant negative correlation was found between SF2 and relative clinical response, but only when averaged high dose-rate SF2 values and telangiectasia scores were compared. There was no significant correlation between average SF2 values and acute responses or between individual SF2 measurements and either the acute or late clinical response. The results of this study suggest that the degree of late telangiectasia is at least partially dependent upon the intrinsic cellular radiosensitivity of normal fibroblasts, but the relationship is not clear cut. Multiple replicate assays are necessary to obtain reliable estimates of fibroblast SF2 values using current techniques. 20 refs., 3 figs., 3 tabs.

  7. Fall diets of red-breasted merganser (Mergus serrator) and walleye (Sander vitreus) in Sandusky Bay and adjacent waters of western Lake Erie

    USGS Publications Warehouse

    Bur, M.T.; Stapanian, M.A.; Bernhardt, G.; Turner, M.W.

    2008-01-01

    Although published studies indicate the contrary, there is concern among many sport anglers that migrating red-breasted mergansers (Mergus serrator) and other waterbirds pose a competitive threat to sport fish species such as walleye (Sander vitreus) in Lake Erie. We quantified the diet of autumn-migrant mergansers and walleye during 1998-2000 in Sandusky Bay and adjacent waters of western Lake Erie. We hypothesized that the diets of both predators would be similar in species composition, but because of different foraging ecologies their diets would differ markedly in size of prey consumed. In addition to predator samples, we used trawl data from the same general area as an index of prey availability. We found that mergansers fed almost exclusively on fish (nine species). Gizzard shad (Dorosoma cepedianum), emerald shiner (Notropis atherinoides) and round goby (Neogobius melanostomus) were consumed in the greatest numbers, most frequently and comprised the greatest biomass. Walleye fed exclusively on fish: gizzard shad, alewife (Alosa psuedoharengus) and emerald shiner were consumed in the greatest numbers, most frequently and comprised the greatest biomass. Diet overlap between mergansers and walleye was 67% by weight and 66% by species frequency. Mean total lengths of gizzard shad, emerald shiner and round goby found in walleye stomachs exceeded those captured in trawls by 47%, on average. Mean total lengths of gizzard shad, emerald shiner and round goby were greater in walleye stomachs than in merganser stomachs. Mean total lengths of emerald shiner and round goby were less in merganser stomachs than in trawls. Our results suggest that although the diets of walleye and mergansers overlapped considerably, mergansers generally consumed smaller fish than walleye. Given the abundance and diversity of prey species available, and the transient nature of mergansers on Lake Erie during migration, we conclude that competition for food between these species is minimal.

  8. Differential sensitivity of normal and malignant breast epithelial cells to genistein is partly mediated by p21(WAF1).

    PubMed

    Upadhyay, S; Neburi, M; Chinni, S R; Alhasan, S; Miller, F; Sarkar, F H

    2001-06-01

    Genistein, a soy metabolite, is a potential chemopreventive agent against various types of cancer. There are several studies documenting molecular alterations leading to cell cycle arrest and induction of apoptosis in a variety of cancer cells; however, no studies, to date, have shown the effect of genistein in isogenic normal and malignant breast epithelial cells. In this study, we investigated whether genistein shows any differential sensitivity to normal (MCF10A and MCF12A) and malignant (MCF10CA1a and MDA-MB-231) breast epithelial cells. We found that genistein causes a greater degree of G(2)-M arrest and induces apoptosis in malignant cell lines compared with normal breast epithelial cells. After genistein treatment, flow cytometric analysis revealed a hyperdiploid population in malignant cells that was not observed in normal cells. Cell cycle regulator p21(WAF1), which is known to be up-regulated by genistein treatment, was greatly induced at RNA and protein levels in normal cells, whereas its level was only slightly induced in malignant MDA-MB-231 cells and not detectable in malignant MCF10CA1a cells. Therefore, we investigated the causal role of p21(WAF1) in the differential sensitivity of genistein among these cell lines. We examined the effects of genistein on p21(WAF1) -/- and p21(WAF1) +/+ HCT116 cells, which were used as controls prior to studies on breast cancer cells. We found that there was a greater degree of cell cycle arrest and apoptosis in p21(WAF1) -/- cells compared with p21(WAF1) +/+ HCT116 cells after genistein treatment. Flow cytometric analysis after genistein treatment showed a significant number of p21(WAF1) -/- cells in the hyperdiploid population, which are probably programmed to die through apoptotic processes. To further confirm the causal role of p21(WAF1) in genistein-mediated cell cycle arrest and apoptosis, we down-regulated p21(WAF1) by antisense p21(WAF1) cDNA transfection experiments. We found that both normal and malignant p

  9. Characterization of cell lines derived from breast cancers and normal mammary tissues for the study of the intrinsic molecular subtypes.

    PubMed

    Prat, Aleix; Karginova, Olga; Parker, Joel S; Fan, Cheng; He, Xiaping; Bixby, Lisa; Harrell, J Chuck; Roman, Erick; Adamo, Barbara; Troester, Melissa; Perou, Charles M

    2013-11-01

    Five molecular subtypes (luminal A, luminal B, HER2-enriched, basal-like, and claudin-low) with clinical implications exist in breast cancer. Here, we evaluated the molecular and phenotypic relationships of (1) a large in vitro panel of human breast cancer cell lines (BCCLs), human mammary fibroblasts (HMFs), and human mammary epithelial cells (HMECs); (2) in vivo breast tumors; (3) normal breast cell subpopulations; (4) human embryonic stem cells (hESCs); and (5) bone marrow-derived mesenchymal stem cells (hMSC). First, by integrating genomic data of 337 breast tumor samples with 93 cell lines we were able to identify all the intrinsic tumor subtypes in the cell lines, except for luminal A. Secondly, we observed that the cell lines recapitulate the differentiation hierarchy detected in the normal mammary gland, with claudin-low BCCLs and HMFs cells showing a stromal phenotype, HMECs showing a mammary stem cell/bipotent progenitor phenotype, basal-like cells showing a luminal progenitor phenotype, and luminal B cell lines showing a mature luminal phenotype. Thirdly, we identified basal-like and highly migratory claudin-low subpopulations of cells within a subset of triple-negative BCCLs (SUM149PT, HCC1143, and HCC38). Interestingly, both subpopulations within SUM149PT were enriched for tumor-initiating cells, but the basal-like subpopulation grew tumors faster than the claudin-low subpopulation. Finally, claudin-low BCCLs resembled the phenotype of hMSCs, whereas hESCs cells showed an epithelial phenotype without basal or luminal differentiation. The results presented here help to improve our understanding of the wide range of breast cancer cell line models through the appropriate pairing of cell lines with relevant in vivo tumor and normal cell counterparts.

  10. A large-scale study of the ultrawideband microwave dielectric properties of normal, benign and malignant breast tissues obtained from cancer surgeries

    NASA Astrophysics Data System (ADS)

    Lazebnik, Mariya; Popovic, Dijana; McCartney, Leah; Watkins, Cynthia B.; Lindstrom, Mary J.; Harter, Josephine; Sewall, Sarah; Ogilvie, Travis; Magliocco, Anthony; Breslin, Tara M.; Temple, Walley; Mew, Daphne; Booske, John H.; Okoniewski, Michal; Hagness, Susan C.

    2007-10-01

    The development of microwave breast cancer detection and treatment techniques has been driven by reports of substantial contrast in the dielectric properties of malignant and normal breast tissues. However, definitive knowledge of the dielectric properties of normal and diseased breast tissues at microwave frequencies has been limited by gaps and discrepancies across previously published studies. To address these issues, we conducted a large-scale study to experimentally determine the ultrawideband microwave dielectric properties of a variety of normal, malignant and benign breast tissues, measured from 0.5 to 20 GHz using a precision open-ended coaxial probe. Previously, we reported the dielectric properties of normal breast tissue samples obtained from reduction surgeries. Here, we report the dielectric properties of normal (adipose, glandular and fibroconnective), malignant (invasive and non-invasive ductal and lobular carcinomas) and benign (fibroadenomas and cysts) breast tissue samples obtained from cancer surgeries. We fit a one-pole Cole-Cole model to the complex permittivity data set of each characterized sample. Our analyses show that the contrast in the microwave-frequency dielectric properties between malignant and normal adipose-dominated tissues in the breast is considerable, as large as 10:1, while the contrast in the microwave-frequency dielectric properties between malignant and normal glandular/fibroconnective tissues in the breast is no more than about 10%.

  11. Non-normal Screening Mammography Results, Lumpectomies, and Breast Cancer Reported by California Women, 2001–2009

    PubMed Central

    Irvin, Veronica L.; Breen, Nancy; Meissner, Helen I.; Liu, Benmei; Kaplan, Robert M.

    2015-01-01

    Background Although screening mammography may contribute to decreases in breast cancer mortality in a population, it may also increase the risk of false positives, anxiety, and unnecessary and costly medical procedures in individuals. We report trends in self-reported non-normal screening mammography results, lumpectomies, and breast cancer in a representative sample of California women. Methods Data were obtained from the 2001, 2005, and 2009 cross-sectional California Health Interview Surveys (CHIS) and weighted to the California population. CHIS employed a multistage sampling design to administer telephone surveys in 6 languages. Our study sample was restricted to women 40 years and older who reported a screening mammogram in the past 2 years. Sample sizes were 13,974 in 2001, 12,069 in 2005, and 15,552 in 2009. Women reporting non-normal results were asked whether they had an operation to remove the lump and, if so, whether the lump was confirmed as malignant. Findings Between 2001 and 2009, the percent of California women who reported having been diagnosed with breast cancer was relatively stable. For each of the three age groups studied, the percentage of non-normal mammography results increased and the percentages of lumpectomies decreased and, for every woman reporting a diagnosis of breast cancer, three women reported a lumpectomy that turned out not to be cancer. This ratio was greater for younger women and less for older women. Conclusions Despite relatively constant rates of breast cancer diagnosis from 2001 to 2009, the percentage of non-normal mammography results increased and lumpectomies declined. PMID:26070253

  12. Expression profiling of cancerous and normal breast tissues identifies microRNAs that are differentially expressed in serum from patients with (metastatic) breast cancer and healthy volunteers

    PubMed Central

    2012-01-01

    Introduction MicroRNAs (miRNAs) are a group of small noncoding RNAs involved in the regulation of gene expression. As such, they regulate a large number of cellular pathways, and deregulation or altered expression of miRNAs is associated with tumorigenesis. In the current study, we evaluated the feasibility and clinical utility of circulating miRNAs as biomarkers for the detection and staging of breast cancer. Methods miRNAs were extracted from a set of 84 tissue samples from patients with breast cancer and eight normal tissue samples obtained after breast-reductive surgery. After reverse transcription and preamplification, 768 miRNAs were profiled by using the TaqMan low-density arrays. After data normalization, unsupervised hierarchical cluster analysis (UHCA) was used to investigate global differences in miRNA expression between cancerous and normal samples. With fold-change analysis, the most discriminating miRNAs between both tissue types were selected, and their expression was analyzed on serum samples from 20 healthy volunteers and 75 patients with breast cancer, including 16 patients with untreated metastatic breast cancer. miRNAs were extracted from 200 μl of serum, reverse transcribed, and analyzed in duplicate by using polymerase chain reaction (qRT-PCR). Results UHCA showed major differences in miRNA expression between tissue samples from patients with breast cancer and tissue samples from breast-reductive surgery (P < 0.0001). Generally, miRNA expression in cancerous samples tends to be repressed when compared with miRNA expression in healthy controls (P = 0.0685). The four most discriminating miRNAs by fold-change (miR-215, miR-299-5p, miR-411, and miR-452) were selected for further analysis on serum samples. All miRNAs at least tended to be differentially expressed between serum samples from patients with cancer and serum samples from healthy controls (miR-215, P = 0.094; miR-299-5P, P = 0.019; miR-411, P = 0.002; and miR-452, P = 0.092). For all

  13. ADAMTS-1 Is Found in the Nuclei of Normal and Tumoral Breast Cells

    PubMed Central

    Silva, Suély V.; Lima, Maíra A.; Cella, Nathalie; Jaeger, Ruy G.

    2016-01-01

    Proteins secreted in the extracellular matrix microenvironment (ECM) by tumor cells are involved in cell adhesion, motility, intercellular communication and invasion. The tumor microenvironment is expansively modified and remodeled by proteases, resulting in important changes in both cell-cell and cell-ECM interactions and in the generation of new signals from the cell surface. Metalloproteinases belonging to the ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family have been implicated in tissue remodeling events observed in cancer development, growth and progression. Here we investigated the subcellular localization of ADAMTS-1 in normal-like (MCF10-A) and tumoral (MCF7 and MDA-MB-231) human breast cells. ADAMTS-1 is a secreted protease found in the extracellular matrix. However, in this study we show for the first time that ADAMTS-1 is also present in the nuclei and nucleoli of the three mammary cell lines studied here. Our findings indicate that ADAMTS-1 has proteolytic functions in the nucleus through its interaction with aggrecan substrate. PMID:27764205

  14. Associations between genetic variation in one-carbon metabolism and LINE-1 DNA methylation in histologically normal breast tissues

    PubMed Central

    Llanos, Adana A M; Marian, Catalin; Brasky, Theodore M; Dumitrescu, Ramona G; Liu, Zhenhua; Mason, Joel B; Makambi, Kepher H; Spear, Scott L; Kallakury, Bhaskar V S; Freudenheim, Jo L; Shields, Peter G

    2015-01-01

    Genome-wide DNA hypomethylation is an early event in the carcinogenic process. Percent methylation of long interspersed nucleotide element-1 (LINE-1) is a biomarker of genome-wide methylation and is a potential biomarker for breast cancer. Understanding factors associated with percent LINE-1 DNA methylation in histologically normal tissues could provide insight into early stages of carcinogenesis. In a cross-sectional study of 121 healthy women with no prior history of cancer who underwent reduction mammoplasty, we examined associations between plasma and breast folate, genetic variation in one-carbon metabolism, and percent LINE-1 methylation using multivariable regression models (adjusting for race, oral contraceptive use, and alcohol use). Results are expressed as the ratio of LINE-1 methylation relative to that of the referent group, with the corresponding 95% confidence intervals (CI). We found no significant associations between plasma or breast folate and percent LINE-1 methylation. Variation in MTHFR, MTR, and MTRR were significantly associated with percent LINE-1 methylation. Variant allele carriers of MTHFR A1289C had 4% lower LINE-1 methylation (Ratio 0.96, 95% CI 0.93–0.98), while variant allele carriers of MTR A2756G (Ratio 1.03, 95% CI 1.01–1.06) and MTRR A66G (Ratio 1.03, 95% CI 1.01–1.06) had 3% higher LINE-1 methylation, compared to those carrying the more common genotypes of these SNPs. DNA methylation of LINE-1 elements in histologically normal breast tissues is influenced by polymorphisms in genes in the one-carbon metabolism pathway. Future studies are needed to investigate the sociodemographic, environmental and additional genetic determinants of DNA methylation in breast tissues and the impact on breast cancer susceptibility. PMID:26090795

  15. A comparison study of different excitation wavelengths to determine the relative content of key biomolecules in breast cancer and breast normal tissue

    NASA Astrophysics Data System (ADS)

    Sordillo, Laura A.; Sordillo, Peter P.; Budansky, Yury; Pu, Yang; Alfano, R. R.

    2015-03-01

    Fluorescence profiles from breast cancer and breast normal tissue samples with excitation wavelengths at 280 nm and 340 nm were obtained using the conventional LS-50 Perkin-Elmer spectrometer. Fluorescence ratios from these tissue samples, demonstrated by emission peaks at 340 nm, 440 nm and 460 nm and likely representing tryptophan and NADH, show increased relative content of tryptophan in malignant samples. Double ratio (DR) techniques were used to measure the severity of disease. The single excitation double ratio (Single-DR) method utilizes the emission intensity peaks from the spectrum acquired using a single excitation of 280 nm; while the dual excitation double ratio (dual-DR) method utilizes the emission intensity peaks from the spectra acquired using an excitation of 280 nm and 340 nm. Single-DR and dual-DR from 13 patients with breast carcinoma were compared in terms of their efficiency to distinguish high from low/intermediate tumors. Similar results were found with both methods. Results suggest that dual excitation wavelengths may be as effective as single excitation wavelength in calculating the relative content of biomolecules in breast cancer tissue, as well as for the assessment of the malignant potential of these tumors.

  16. Reliability of quantitative ultrasonic assessment of normal-tissue toxicity in breast cancer radiotherapy

    PubMed Central

    Yoshida, Emi J.; Chen, Hao; Torres, Mylin; Andic, Fundagul; Liu, Hao-Yang; Chen, Zhengjia; Sun, Xiaoyan; Curran, Walter J; Liu, Tian

    2011-01-01

    Purpose We have recently reported that ultrasound imaging, together with ultrasound tissue characterization (UTC), can provide quantitative assessment of radiation-induced normal-tissue toxicity. This study’s purpose is to evaluate the reliability of our quantitative ultrasound technology in assessing acute and late normal-tissue toxicity in breast cancer radiotherapy. Method and Materials Our ultrasound technique analyzes radio-frequency echo signals and provides quantitative measures of dermal, hypodermal, and glandular-tissue toxicities. To facilitate easy clinical implementation, we further refined this technique by developing a semi-automatic ultrasound-based toxicity assessment tool (UBTAT). Seventy-two ultrasound studies of 26 patients (720 images) were analyzed. Images of 8 patients were evaluated for acute toxicity (<6 months post radiotherapy) and those of 18 patients were evaluated for late toxicity (≥6 months post radiotherapy). All patients were treated according to a standard radiotherapy protocol. To assess intra-observer reliability, one observer analyzed 720 images in UBTAT and then repeated the analysis 3 months later. To assess inter-observer reliability, three observers (two radiation oncologists and one ultrasound expert) each analyzed 720 images in UBTAT. An intraclass correlation coefficient (ICC) was used to evaluate intra- and inter-observer reliability. Ultrasound assessment and clinical evaluation were also compared. Results Intra-observer ICC was 0.89 for dermal toxicity, 0.74 for hypodermal toxicity, and 0.96 for glandular-tissue toxicity. Inter-observer ICC was 0.78 for dermal toxicity, 0.74 for hypodermal toxicity, and 0.94 for glandular-tissue toxicity. Statistical analysis found significant changes in dermal (p < 0.0001), hypodermal (p=0.0027), and glandular-tissue (p < 0.0001) assessments in the acute toxicity group. Ultrasound measurements correlated with clinical RTOG toxicity scores of patients in the late toxicity group

  17. Vitamin D and the mammary gland: a review on its role in normal development and breast cancer.

    PubMed

    Lopes, Nair; Paredes, Joana; Costa, José Luis; Ylstra, Bauke; Schmitt, Fernando

    2012-05-31

    Breast cancer is a heterogeneous disease associated with diverse biological behaviours and clinical outcome. Although some molecular subgroups of breast cancer have a targeted therapy, the most aggressive tumours still lack a molecular target. Despite vitamin D being classically associated with the physiological role of calcium regulation and phosphate transport in bone metabolism, several studies have demonstrated a wide range of functions for this hormone, which are particularly important in the field of cancer. The mechanisms underlying the protective actions of vitamin D in cancer development are only sparsely understood, but evidence shows that vitamin D participates in cell growth regulation, apoptosis and cell differentiation. In addition, it has been implicated in the suppression of cancer cell invasion, angiogenesis and metastasis. Most of vitamin D biological actions are mediated by the vitamin D receptor and the synthesis and catabolism of this hormone are regulated by the enzymes CYP27B1 and CYP24A1. In the present review we highlight research data concerning the function of this hormone in the mammary gland, with a special focus on breast carcinogenesis. Hence, and although the available data are controversial, we consider not only updated information on the epidemiology of vitamin D in breast cancer and its potential value as a therapeutic agent or prophylactic (with an emphasis on molecular mechanisms and effectors of vitamin D action), but include data on its role in other stages of breast cancer progression as well. Accordingly, we review data on the influence of vitamin D in the development of normal breast and the expression of vitamin D-related proteins (VDR, CYP27B1 and CYP24A21) in benign mammary lesions and ductal carcinomas in situ.

  18. Breast lump

    MedlinePlus

    Breast mass ... males and females of all ages have normal breast tissue. This tissue responds to hormone changes. Because of this, lumps can come and go. Breast lumps may appear at any age: Both male ...

  19. Effects of BRCA2 cis-regulation in normal breast and cancer risk amongst BRCA2 mutation carriers

    PubMed Central

    2012-01-01

    Introduction Cis-acting regulatory single nucleotide polymorphisms (SNPs) at specific loci may modulate penetrance of germline mutations at the same loci by introducing different levels of expression of the wild-type allele. We have previously reported that BRCA2 shows differential allelic expression and we hypothesize that the known variable penetrance of BRCA2 mutations might be associated with this mechanism. Methods We combined haplotype analysis and differential allelic expression of BRCA2 in breast tissue to identify expression haplotypes and candidate cis-regulatory variants. These candidate variants underwent selection based on in silico predictions for regulatory potential and disruption of transcription factor binding, and were functionally analyzed in vitro and in vivo in normal and breast cancer cell lines. SNPs tagging the expression haplotypes were correlated with the total expression of several genes in breast tissue measured by Taqman and microarray technologies. The effect of the expression haplotypes on breast cancer risk in BRCA2 mutation carriers was investigated in 2,754 carriers. Results We identified common haplotypes associated with differences in the levels of BRCA2 expression in human breast cells. We characterized three cis-regulatory SNPs located at the promoter and two intronic regulatory elements which affect the binding of the transcription factors C/EBPα, HMGA1, D-binding protein (DBP) and ZF5. We showed that the expression haplotypes also correlated with changes in the expression of other genes in normal breast. Furthermore, there was suggestive evidence that the minor allele of SNP rs4942440, which is associated with higher BRCA2 expression, is also associated with a reduced risk of breast cancer (per-allele hazard ratio (HR) = 0.85, 95% confidence interval (CI) = 0.72 to 1.00, P-trend = 0.048). Conclusions Our work provides further insights into the role of cis-regulatory variation in the penetrance of disease-causing mutations

  20. Discrimination between normal breast tissue and tumor tissue using CdTe series detector developed for photon-counting mammography

    NASA Astrophysics Data System (ADS)

    Okamoto, Chizuru; Ihori, Akiko; Yamakawa, Tsutomu; Yamamoto, Shuichiro; Okada, Masahiro; Kato, Misa; Nakajima, Ai; Kodera, Yoshie

    2016-03-01

    We propose a new mammography system using a cadmium telluride (CdTe) series photon-counting detector, having high absorption efficiency over a wide energy range. In a previous study, we showed that the use of high X-ray energy in digital mammography is useful from the viewpoint of exposure dose and image quality. In addition, the CdTe series detector can acquire X-ray spectrum information following transmission through a subject. This study focused on the tissue composition identified using spectral information obtained by a new photon-counting detector. Normal breast tissue consists entirely of adipose and glandular tissues. However, it is very difficult to find tumor tissue in the region of glandular tissue via a conventional mammogram, especially in dense breast because the attenuation coefficients of glandular tissue and tumor tissue are very close. As a fundamental examination, we considered a simulation phantom and showed the difference between normal breast tissue and tumor tissue of various thicknesses in a three-dimensional (3D) scatter plot. We were able to discriminate between both types of tissues. In addition, there was a tendency for the distribution to depend on the thickness of the tumor tissue. Thinner tumor tissues were shown to be closer in appearance to normal breast tissue. This study also demonstrated that the difference between these tissues could be made obvious by using a CdTe series detector. We believe that this differentiation is important, and therefore, expect this technology to be applied to new tumor detection systems in the future.

  1. Electromagnetic spectroscopy of normal breast tissue specimens obtained from reduction surgeries: comparison of optical and microwave properties.

    PubMed

    Lazebnik, Mariya; Zhu, Changfang; Palmer, Gregory M; Harter, Josephine; Sewall, Sarah; Ramanujam, Nirmala; Hagness, Susan C

    2008-10-01

    Techniques utilizing electromagnetic energy at microwave and optical frequencies have been shown to be promising for breast cancer detection and diagnosis. Since different biophysical mechanisms are exploited at these frequencies to discriminate between healthy and diseased tissue, combining these two modalities may result in a more powerful approach for breast cancer detection and diagnosis. Toward this end, we performed microwave dielectric spectroscopy and optical diffuse reflectance spectroscopy measurements at the same sites on freshly excised normal breast tissues obtained from reduction surgeries at the University of Wisconsin Hospital, using microwave and optical probes with very similar sensing volumes. We found that the microwave dielectric constant and effective conductivity are correlated with tissue composition across the entire measurement frequency range (|r| approximately 0.5-0.6, p<0.01) and that the optical absorption coefficient at 460 nm and optical scattering coefficient are correlated with tissue composition (|r| approximately 0.4-0.6, p<0.02). Finally, we found that the optical absorption coefficient at 460 nm is correlated with the microwave dielectric constant and effective conductivity (r=-0.55, p<0.01). Our results suggest that combining optical and microwave modalities for analyzing breast tissue samples may serve as a crosscheck and provide complementary information about tissue composition.

  2. Correction of electrode polarization contributions to the dielectric properties of normal and cancerous breast tissues at audio/radiofrequencies

    NASA Astrophysics Data System (ADS)

    Stoneman, M. R.; Kosempa, M.; Gregory, W. D.; Gregory, C. W.; Marx, J. J.; Mikkelson, W.; Tjoe, J.; Raicu, V.

    2007-11-01

    Spurious contributions from electrode polarization (EP) are a major nuisance in dielectric measurements of biological tissues and hamper accurate determination of tissue properties in the audio/radiofrequencies. Various electrode geometries and/or treatments have been employed traditionally to reduce EP contributions, although none succeeded to completely remove EP from measurements on tissues for all practical frequency ranges. A method of correction for contributions of EP to the dielectric properties of tissues is proposed. The method is based on modeling the electrode impedance with suitable functions and on the observation that certain parameters are only dependent on electrodes properties and can thus be determined separately. The method is tested on various samples with known properties, and its usefulness is demonstrated with samples of normal and cancerous human female breast tissue. It is observed that the dielectric properties of the tissues over the frequency range 40 Hz-100 MHz are significantly different among different types of breast tissue. This observation is used further to demonstrate that, by scanning the tip of the measuring dielectric probe (with modest spatial resolution) across a sample of excised breast tissue, significant variations in the electrical properties are detected at a position where a tumor is located. This study shows that dielectric spectroscopy has the potential to offer a viable alternative to the current methods for detection of breast cancer in vivo.

  3. Identification of novel breast cancer-associated transcripts by UniGene database mining and gene expression analysis in normal and malignant cells.

    PubMed

    Laversin, Stéphanie A-S; Phatak, Vinaya M; Powe, Des G; Li, Geng; Miles, Amanda K; Hughes, David C; Ball, Graham R; Ellis, Ian O; Gritzapis, Angelos D; Missitzis, Ioannis; McArdle, Stéphanie E B; Rees, Robert C

    2013-03-01

    Breast cancer is a heterogeneous and complex disease. Although the use of tumor biomarkers has improved individualized breast cancer care, i.e., assessment of risk, diagnosis, prognosis, and prediction of treatment outcome, new markers are required to further improve patient clinical management. In the present study, a search for novel breast cancer-associated genes was performed by mining the UniGene database for expressed sequence tags (ESTs) originating from human normal breast, breast cancer tissue, or breast cancer cell lines. Two hundred and twenty-eight distinct breast-associated UniGene Clusters (BUC1-228) matched the search criteria. Four BUC ESTs (BUC6, BUC9, BUC10, and BUC11) were subsequently selected for extensive in silico database searches, and in vitro analyses through sequencing and RT-PCR based assays on well-characterized cell lines and tissues of normal and cancerous origin. BUC6, BUC9, BUC10, and BUC11 are clustered on 10p11.21-12.1 and showed no homology to any known RNAs. Overall, expression of the four BUC transcripts was high in normal breast and testis tissue, and in some breast cancers; in contrast, BUC was low in other normal tissues, peripheral blood mononuclear cells (PBMCs), and other cancer cell lines. Results to-date suggest that BUC11 and BUC9 translate to protein and BUC11 cytoplasmic and nuclear protein expression was detected in a large cohort of breast cancer samples using immunohistochemistry. This study demonstrates the discovery and expression analysis of a tissue-restricted novel transcript set which is strongly expressed in breast tissue and their application as clinical cancer biomarkers clearly warrants further investigation.

  4. Isotropic 3D Nuclear Morphometry of Normal, Fibrocystic and Malignant Breast Epithelial Cells Reveals New Structural Alterations

    PubMed Central

    Nandakumar, Vivek; Kelbauskas, Laimonas; Hernandez, Kathryn F.; Lintecum, Kelly M.; Senechal, Patti; Bussey, Kimberly J.; Davies, Paul C. W.; Johnson, Roger H.; Meldrum, Deirdre R.

    2012-01-01

    Background Grading schemes for breast cancer diagnosis are predominantly based on pathologists' qualitative assessment of altered nuclear structure from 2D brightfield microscopy images. However, cells are three-dimensional (3D) objects with features that are inherently 3D and thus poorly characterized in 2D. Our goal is to quantitatively characterize nuclear structure in 3D, assess its variation with malignancy, and investigate whether such variation correlates with standard nuclear grading criteria. Methodology We applied micro-optical computed tomographic imaging and automated 3D nuclear morphometry to quantify and compare morphological variations between human cell lines derived from normal, benign fibrocystic or malignant breast epithelium. To reproduce the appearance and contrast in clinical cytopathology images, we stained cells with hematoxylin and eosin and obtained 3D images of 150 individual stained cells of each cell type at sub-micron, isotropic resolution. Applying volumetric image analyses, we computed 42 3D morphological and textural descriptors of cellular and nuclear structure. Principal Findings We observed four distinct nuclear shape categories, the predominant being a mushroom cap shape. Cell and nuclear volumes increased from normal to fibrocystic to metastatic type, but there was little difference in the volume ratio of nucleus to cytoplasm (N/C ratio) between the lines. Abnormal cell nuclei had more nucleoli, markedly higher density and clumpier chromatin organization compared to normal. Nuclei of non-tumorigenic, fibrocystic cells exhibited larger textural variations than metastatic cell nuclei. At p<0.0025 by ANOVA and Kruskal-Wallis tests, 90% of our computed descriptors statistically differentiated control from abnormal cell populations, but only 69% of these features statistically differentiated the fibrocystic from the metastatic cell populations. Conclusions Our results provide a new perspective on nuclear structure variations

  5. Growth hormone is secreted by normal breast epithelium upon progesterone stimulation and increases proliferation of stem/progenitor cells.

    PubMed

    Lombardi, Sara; Honeth, Gabriella; Ginestier, Christophe; Shinomiya, Ireneusz; Marlow, Rebecca; Buchupalli, Bharath; Gazinska, Patrycja; Brown, John; Catchpole, Steven; Liu, Suling; Barkan, Ariel; Wicha, Max; Purushotham, Anand; Burchell, Joy; Pinder, Sarah; Dontu, Gabriela

    2014-06-01

    Using in vitro and in vivo experimental systems and in situ analysis, we show that growth hormone (GH) is secreted locally by normal human mammary epithelial cells upon progesterone stimulation. GH increases proliferation of a subset of cells that express growth hormone receptor (GHR) and have functional properties of stem and early progenitor cells. In 72% of ductal carcinoma in situ lesions, an expansion of the cell population that expresses GHR was observed, suggesting that GH signaling may contribute to breast cancer development.

  6. Developing Multivariable Normal Tissue Complication Probability Model to Predict the Incidence of Symptomatic Radiation Pneumonitis among Breast Cancer Patients

    PubMed Central

    Chang, Liyun; Ting, Hui-Min; Huang, Yu-Jie

    2015-01-01

    Purpose Symptomatic radiation pneumonitis (SRP), which decreases quality of life (QoL), is the most common pulmonary complication in patients receiving breast irradiation. If it occurs, acute SRP usually develops 4–12 weeks after completion of radiotherapy and presents as a dry cough, dyspnea and low-grade fever. If the incidence of SRP is reduced, not only the QoL but also the compliance of breast cancer patients may be improved. Therefore, we investigated the incidence SRP in breast cancer patients after hybrid intensity modulated radiotherapy (IMRT) to find the risk factors, which may have important effects on the risk of radiation-induced complications. Methods In total, 93 patients with breast cancer were evaluated. The final endpoint for acute SRP was defined as those who had density changes together with symptoms, as measured using computed tomography. The risk factors for a multivariate normal tissue complication probability model of SRP were determined using the least absolute shrinkage and selection operator (LASSO) technique. Results Five risk factors were selected using LASSO: the percentage of the ipsilateral lung volume that received more than 20-Gy (IV20), energy, age, body mass index (BMI) and T stage. Positive associations were demonstrated among the incidence of SRP, IV20, and patient age. Energy, BMI and T stage showed a negative association with the incidence of SRP. Our analyses indicate that the risk of SPR following hybrid IMRT in elderly or low-BMI breast cancer patients is increased once the percentage of the ipsilateral lung volume receiving more than 20-Gy is controlled below a limitation. Conclusions We suggest to define a dose-volume percentage constraint of IV20< 37% (or AIV20< 310cc) for the irradiated ipsilateral lung in radiation therapy treatment planning to maintain the incidence of SPR below 20%, and pay attention to the sequelae especially in elderly or low-BMI breast cancer patients. (AIV20: the absolute ipsilateral lung

  7. Analysis of cell surface carbohydrate expression patterns in normal and tumorigenic human breast cell lines using lectin arrays.

    PubMed

    Chen, Siyuan; Zheng, Ting; Shortreed, Michael R; Alexander, Caroline; Smith, Lloyd M

    2007-08-01

    Cell surface carbohydrates play important roles in a wide variety of biological processes including cell adhesion, fertilization, differentiation, development, and tumor cell metastasis. Lectins are proteins of nonimmune origin which recognize and bind to specific carbohydrate structural epitopes. We have recently described the development and use of lectin arrays as tools for the elucidation of the carbohydrate structures expressed on cell surfaces. In the present work this technology is employed for the characterization of differences in carbohydrate expression patterns on normal and tumorigenic human breast cell lines, as well as on sublines differing in their tendency to "home" to different tissues during metastasis. Significant differences were observed, including changes that correlate with metastatic potential as well as with tissue-specific homing of metastatic cells.

  8. Role of vascular density and normalization in response to neoadjuvant bevacizumab and chemotherapy in breast cancer patients.

    PubMed

    Tolaney, Sara M; Boucher, Yves; Duda, Dan G; Martin, John D; Seano, Giorgio; Ancukiewicz, Marek; Barry, William T; Goel, Shom; Lahdenrata, Johanna; Isakoff, Steven J; Yeh, Eren D; Jain, Saloni R; Golshan, Mehra; Brock, Jane; Snuderl, Matija; Winer, Eric P; Krop, Ian E; Jain, Rakesh K

    2015-11-17

    Preoperative bevacizumab and chemotherapy may benefit a subset of breast cancer (BC) patients. To explore potential mechanisms of this benefit, we conducted a phase II study of neoadjuvant bevacizumab (single dose) followed by combined bevacizumab and adriamycin/cyclophosphamide/paclitaxel chemotherapy in HER2-negative BC. The regimen was well-tolerated and showed a higher rate of pathologic complete response (pCR) in triple-negative (TN)BC (11/21 patients or 52%, [95% confidence interval (CI): 30,74]) than in hormone receptor-positive (HR)BC [5/78 patients or 6% (95%CI: 2,14)]. Within the HRBCs, basal-like subtype was significantly associated with pCR (P = 0.007; Fisher exact test). We assessed interstitial fluid pressure (IFP) and tissue biopsies before and after bevacizumab monotherapy and circulating plasma biomarkers at baseline and before and after combination therapy. Bevacizumab alone lowered IFP, but to a smaller extent than previously observed in other tumor types. Pathologic response to therapy correlated with sVEGFR1 postbevacizumab alone in TNBC (Spearman correlation 0.610, P = 0.0033) and pretreatment microvascular density (MVD) in all patients (Spearman correlation 0.465, P = 0.0005). Moreover, increased pericyte-covered MVD, a marker of extent of vascular normalization, after bevacizumab monotherapy was associated with improved pathologic response to treatment, especially in patients with a high pretreatment MVD. These data suggest that bevacizumab prunes vessels while normalizing those remaining, and thus is beneficial only when sufficient numbers of vessels are initially present. This study implicates pretreatment MVD as a potential predictive biomarker of response to bevacizumab in BC and suggests that new therapies are needed to normalize vessels without pruning.

  9. Role of vascular density and normalization in response to neoadjuvant bevacizumab and chemotherapy in breast cancer patients

    PubMed Central

    Tolaney, Sara M.; Boucher, Yves; Duda, Dan G.; Martin, John D.; Seano, Giorgio; Ancukiewicz, Marek; Barry, William T.; Goel, Shom; Lahdenrata, Johanna; Isakoff, Steven J.; Yeh, Eren D.; Jain, Saloni R.; Golshan, Mehra; Brock, Jane; Snuderl, Matija; Winer, Eric P.; Krop, Ian E.; Jain, Rakesh K.

    2015-01-01

    Preoperative bevacizumab and chemotherapy may benefit a subset of breast cancer (BC) patients. To explore potential mechanisms of this benefit, we conducted a phase II study of neoadjuvant bevacizumab (single dose) followed by combined bevacizumab and adriamycin/cyclophosphamide/paclitaxel chemotherapy in HER2-negative BC. The regimen was well-tolerated and showed a higher rate of pathologic complete response (pCR) in triple-negative (TN)BC (11/21 patients or 52%, [95% confidence interval (CI): 30,74]) than in hormone receptor-positive (HR)BC [5/78 patients or 6% (95%CI: 2,14)]. Within the HRBCs, basal-like subtype was significantly associated with pCR (P = 0.007; Fisher exact test). We assessed interstitial fluid pressure (IFP) and tissue biopsies before and after bevacizumab monotherapy and circulating plasma biomarkers at baseline and before and after combination therapy. Bevacizumab alone lowered IFP, but to a smaller extent than previously observed in other tumor types. Pathologic response to therapy correlated with sVEGFR1 postbevacizumab alone in TNBC (Spearman correlation 0.610, P = 0.0033) and pretreatment microvascular density (MVD) in all patients (Spearman correlation 0.465, P = 0.0005). Moreover, increased pericyte-covered MVD, a marker of extent of vascular normalization, after bevacizumab monotherapy was associated with improved pathologic response to treatment, especially in patients with a high pretreatment MVD. These data suggest that bevacizumab prunes vessels while normalizing those remaining, and thus is beneficial only when sufficient numbers of vessels are initially present. This study implicates pretreatment MVD as a potential predictive biomarker of response to bevacizumab in BC and suggests that new therapies are needed to normalize vessels without pruning. PMID:26578779

  10. Identification of Differentially Expressed IGFBP5-Related Genes in Breast Cancer Tumor Tissues Using cDNA Microarray Experiments.

    PubMed

    Akkiprik, Mustafa; Peker, İrem; Özmen, Tolga; Amuran, Gökçe Güllü; Güllüoğlu, Bahadır M; Kaya, Handan; Özer, Ayşe

    2015-11-10

    IGFBP5 is an important regulatory protein in breast cancer progression. We tried to identify differentially expressed genes (DEGs) between breast tumor tissues with IGFBP5 overexpression and their adjacent normal tissues. In this study, thirty-eight breast cancer and adjacent normal breast tissue samples were used to determine IGFBP5 expression by qPCR. cDNA microarrays were applied to the highest IGFBP5 overexpressed tumor samples compared to their adjacent normal breast tissue. Microarray analysis revealed that a total of 186 genes were differentially expressed in breast cancer compared with normal breast tissues. Of the 186 genes, 169 genes were downregulated and 17 genes were upregulated in the tumor samples. KEGG pathway analyses showed that protein digestion and absorption, focal adhesion, salivary secretion, drug metabolism-cytochrome P450, and phenylalanine metabolism pathways are involved. Among these DEGs, the prominent top two genes (MMP11 and COL1A1) which potentially correlated with IGFBP5 were selected for validation using real time RT-qPCR. Only COL1A1 expression showed a consistent upregulation with IGFBP5 expression and COL1A1 and MMP11 were significantly positively correlated. We concluded that the discovery of coordinately expressed genes related with IGFBP5 might contribute to understanding of the molecular mechanism of the function of IGFBP5 in breast cancer. Further functional studies on DEGs and association with IGFBP5 may identify novel biomarkers for clinical applications in breast cancer.

  11. Genomic and mutational profiling of ductal carcinomas in situ and matched adjacent invasive breast cancers reveals intra-tumour genetic heterogeneity and clonal selection

    PubMed Central

    Lambros, Maryou B; Campion-Flora, Adriana; Rodrigues, Daniel Nava; Gauthier, Arnaud; Cabral, Cecilia; Pawar, Vidya; Mackay, Alan; A’Hern, Roger; Marchiò, Caterina; Palacios, Jose; Natrajan, Rachael; Weigelt, Britta; Reis-Filho, Jorge S

    2016-01-01

    The mechanisms underlying the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) of the breast are yet to be fully elucidated. Several hypotheses have been put forward to explain the progression from DCIS to IDC, including the selection of a subpopulation of cancer cells with specific genetic aberrations, the acquisition of new genetic aberrations or non-genetic mechanisms mediated by the tumour microenvironment. To determine whether synchronously diagnosed ipsilateral DCIS and IDCs have modal populations with distinct repertoires of gene copy number aberrations and mutations in common oncogenes, matched frozen samples of DCIS and IDCs were retrieved from 13 patients and subjected to microarray-based comparative genomic hybridisation (aCGH), and Sequenom MassARRAY (Oncocarta v1.0 panel). Fluorescence in situ hybridisation and Sanger sequencing were employed to validate the aCGH and Sequenom findings, respectively. Although the genomic profiles of matched DCIS and IDCs were similar, in three of 13 matched pairs amplification of distinct loci (i.e. 1q41, 2q24.2, 6q22.31, 7q11.21, 8q21.2 and 9p13.3) was either restricted to, or more prevalent in, the modal population of cancer cells of one of the components. Sequenom MassARRAY identified PIK3CA mutations restricted to the DCIS component in two cases, and in a third case, the frequency of the PIK3CA mutant allele reduced from 49% in the DCIS to 25% in the IDC component. Despite the genomic similarities between synchronous DCIS and IDC, our data provide strong circumstantial evidence to suggest that in some cases the progression from DCIS to IDC is driven by the selection of non-modal clones that harbour a specific repertoire of genetic aberrations. PMID:22252965

  12. TU-F-12A-09: GLCM Texture Analysis for Normal-Tissue Toxicity: A Prospective Ultrasound Study of Acute Toxicity in Breast-Cancer Radiotherapy

    SciTech Connect

    Liu, T; Yang, X; Curran, W; Torres, M

    2014-06-15

    Purpose: To evaluate the morphologic and structural integrity of the breast glands using sonographic textural analysis, and identify potential early imaging signatures for radiation toxicity following breast-cancer radiotherapy (RT). Methods: Thirty-eight patients receiving breast RT participated in a prospective ultrasound imaging study. Each participant received 3 ultrasound scans: 1 week before RT (baseline), and at 6-week and 3-month follow-ups. Patients were imaged with a 10-MHz ultrasound on the four quadrant of the breast. A second order statistical method of texture analysis, called gray level co-occurrence matrix (GLCM), was employed to assess RT-induced breast-tissue toxicity. The region of interest (ROI) was 28 mm × 10 mm in size at a 10 mm depth under the skin. Twenty GLCM sonographic features, ratios of the irradiated breast and the contralateral breast, were used to quantify breast-tissue toxicity. Clinical assessment of acute toxicity was conducted using the RTOG toxicity scheme. Results: Ninety-seven ultrasound studies (776 images) were analyzed; and 5 out of 20 sonographic features showed significant differences (p < 0.05) among the baseline scans, the acute toxicity grade 1 and 2 groups. These sonographic features quantified the degree of tissue damage through homogeneity, heterogeneity, randomness, and symmetry. Energy ratio value decreased from 108±0.05 (normal) to 0.99±0.05 (Grade 1) and 0.84±0.04 (Grade 2); Entropy ratio value increased from 1.01±0.01 to 1.02±0.01 and 1.04±0.01; Contrast ratio value increased from 1.03±0.03 to 1.07±0.06 and 1.21±0.09; Variance ratio value increased from 1.06±0.03 to 1.20±0.04 and 1.42±0.10; Cluster Prominence ratio value increased from 0.98±0.02 to 1.01±0.04 and 1.25±0.07. Conclusion: This work has demonstrated that the sonographic features may serve as imaging signatures to assess radiation-induced normal tissue damage. While these findings need to be validated in a larger cohort, they suggest

  13. Sclerotium rolfsii Lectin Induces Stronger Inhibition of Proliferation in Human Breast Cancer Cells than Normal Human Mammary Epithelial Cells by Induction of Cell Apoptosis

    PubMed Central

    Savanur, Mohammed Azharuddin; Eligar, Sachin M.; Pujari, Radha; Chen, Chen; Mahajan, Pravin; Borges, Anita; Shastry, Padma; Ingle, Arvind.; Kalraiya, Rajiv D.; Swamy, Bale M.; Rhodes, Jonathan M.; Yu, Lu-Gang; Inamdar, Shashikala R.

    2014-01-01

    Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). SRL caused marked, dose-dependent, inhibition of proliferation of MCF-7 and ZR-75 cells but only weak inhibition of proliferation of non-tumorigenic MCF-10A and HMEC cells. The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. Lectin histochemistry using biotin-labelled SRL showed little binding of SRL to normal human breast tissue but intense binding to cancerous tissues. In conclusion, SRL inhibits the growth of human breast cancer cells via induction of cell apoptosis but has substantially less effect on normal epithelial cells. As a lectin that binds specifically to a cancer-associated glycan, has potential to be developed as an anti-cancer agent. PMID:25364905

  14. The organizing principle: microenvironmental influences in the normal and malignant breast

    SciTech Connect

    Bissell, Mina; Radisky, Derek C.; Rizki, Aylin; Weaver, Valerie M.; Petersen, Ole W.

    2002-08-20

    The current paradigm for cancer initiation and progression rests on the groundbreaking discoveries of oncogenes and tumor suppressor genes. This framework has revealed much about the role of genetic alterations in the underlying signaling pathways central to normal cellular function and to tumor progression. However, it is clear that single gene theories or even sequential acquisition of mutations underestimate the nature of the genetic and epigenetic changes in tumors, and do not account for the observation that many cancer susceptibility genes (e.g. BRCA1, APC) show a high degree of tissue specificity in their association with neoplastic transformation. Therefore, the cellular and tissue context itself must confer additional and crucial information necessary for mutated genes to exert their influence. A considerable body of evidence now shows that cell - cell and cell - extracellular matrix (ECM) interactions are essential organizing principles that help define the nature of the tissue context, and play a crucial role in regulating homeostasis and tissue specificity. How this context determines functional integrity, and how its loss can lead to malignancy, appears to have much to do with tissue structure and polarity.

  15. Time-resolved fluorescence for breast cancer detection using an octreotate-indocyanine green derivative dye conjugate

    NASA Astrophysics Data System (ADS)

    Sordillo, Laura A.; Das, B. B.; Pu, Yang; Liang, Kexian; Milione, Giovanni; Sordillo, Peter P.; Achilefu, Sam; Alfano, R. R.

    2013-03-01

    Time-resolved fluorescence was used to investigate malignant and normal adjacent breast tissues stained with a conjugate of indocyanine green and octreotate. A marked increase in fluorescence lifetime intensity was seen in the breast cancer sample compared to the normal sample. The fluorescent lifetimes were also investigated and showed similar fluorescence decay curves in stained malignant and normal breast tissue. These results confirm that somatostatin receptors occur on human breast carcinomas, suggest that the presence of somatostatin receptors should be investigated as a marker of breast cancer aggressiveness, and suggest that this conjugate might be used to detect the presence of residual breast cancer after surgery, allowing better assessment of tumor margins and reducing the need for second or repeat biopsies in selected patients. These results may also provide clues for designing future treatment options for breast cancer patients.

  16. Histological and immunohistochemical study of estrogen and progesterone receptors in normal human breast tissue in adult age groups vulnerable to malignancy.

    PubMed

    Goyal, R; Gupta, T; Gupta, R; Aggarwal, A; Sahni, D; Singh, G

    2016-09-01

    Analysis of receptor status has become standard procedure for assessing breast cancer patients. Estrogen causes epithelial proliferation in breast tissue via the estrogen receptor (ER). The progesterone receptor (PR) is also regulated by the estrogen gene. Analyzing ER and PR together gives information regarding the likely response of carcinoma patients to hormonal therapy. The aim of the present study was to record the expression patterns of ER and PR in normal mammary tissue in different age groups to provide reference data to facilitate histological diagnosis. Breast tissues from the upper outer quadrant of each side of 27 adult female cadavers were examined after H & E staining. ER and PR were identified and examined by immunohistochemistry. The percentage area occupied by parenchyma relative to stromal tissue was calculated in different age groups and was about 4:6, 3.5:6.5, 3:7, 2:8, and 1.5:8.5 in the 3rd, 4th and 5th, 6th, 7th, 8th and 9th, and 10th decades of life, respectively. Both ER and PR were present in all age groups and the numbers of both receptors were maximal during the 4th decade. The distribution and staining patterns for both ER and PR were recorded in different age groups. The contiguous pattern of ER, which is considered pathognomonic of breast carcinoma, was not seen except in one case in the 6th decade. Moderately stained ER and PR receptor sites predominated throughout. The study of normal breast tissue of similar age might provide comparisons that will help histopathologists to make clinical diagnoses from breast biopsies. Clin. Anat. 29:729-737, 2016. © 2016 Wiley Periodicals, Inc. PMID:27038435

  17. The Microbiota of Breast Tissue and Its Association with Breast Cancer

    PubMed Central

    Urbaniak, Camilla; Gloor, Gregory B.; Brackstone, Muriel; Scott, Leslie; Tangney, Mark

    2016-01-01

    ABSTRACT In the United States, 1 in 8 women will be diagnosed with breast cancer in her lifetime. Along with genetics, the environment contributes to disease development, but what these exact environmental factors are remains unknown. We have previously shown that breast tissue is not sterile but contains a diverse population of bacteria. We thus believe that the host's local microbiome could be modulating the risk of breast cancer development. Using 16S rRNA amplicon sequencing, we show that bacterial profiles differ between normal adjacent tissue from women with breast cancer and tissue from healthy controls. Women with breast cancer had higher relative abundances of Bacillus, Enterobacteriaceae and Staphylococcus. Escherichia coli (a member of the Enterobacteriaceae family) and Staphylococcus epidermidis, isolated from breast cancer patients, were shown to induce DNA double-stranded breaks in HeLa cells using the histone-2AX (H2AX) phosphorylation (γ-H2AX) assay. We also found that microbial profiles are similar between normal adjacent tissue and tissue sampled directly from the tumor. This study raises important questions as to what role the breast microbiome plays in disease development or progression and how we can manipulate this for possible therapeutics or prevention. IMPORTANCE This study shows that different bacterial profiles in breast tissue exist between healthy women and those with breast cancer. Higher relative abundances of bacteria that had the ability to cause DNA damage in vitro were detected in breast cancer patients, as was a decrease in some lactic acid bacteria, known for their beneficial health effects, including anticarcinogenic properties. This study raises important questions as to the role of the mammary microbiome in modulating the risk of breast cancer development. PMID:27342554

  18. Acoustic radiation force impulse imaging with virtual touch tissue quantification: measurements of normal breast tissue and dependence on the degree of pre-compression.

    PubMed

    Wojcinski, Sebastian; Brandhorst, Kathrin; Sadigh, Gelareh; Hillemanns, Peter; Degenhardt, Friedrich

    2013-12-01

    Acoustic radiation force impulse imaging (ARFI) with Virtual Touch tissue quantification (VTTQ) enables the determination of shear wave velocity in meters per second (m/s). We investigated shear wave velocity in normal breast tissue and analyzed the influence of the degree of pre-compression on the measurements. In repeated measurements and with normal pre-compression, the mean shear wave velocity in breast parenchyma was significantly higher than that in breast adipose tissue (3.33 ± 1.18 m/s vs. 2.90 ± 1.10 m/s; p < 0.001; 712 measurements in 89 patients). Furthermore, we found a significant positive correlation between degree of pre-compression and velocity measurements. Shear wave velocities with low, moderate and high pre-compression were 1.89, 3.18 and 4.39 m/s in parenchyma, compared with 1.46, 2.55 and 3.64 m/s in adipose tissue, respectively (p < 0.001; 360 measurements in 60 patients). VTTQ of breast tissue is a feasible method with high accuracy; however, the degree of pre-compression applied may significantly influence the measurements.

  19. Normal and tumor-derived myoepithelial cells differ in their ability to interact with luminal breast epithelial cells for polarity and basement membrane deposition

    SciTech Connect

    Gudjonsson, Thorarinn; Ronnov-Jessen, Lone; Villadsen, Rene; Rank, Fritz; Bissell, Mina J.; Petersen, Ole William

    2001-10-04

    The signals that determine the correct polarity of breast epithelial structures in vivo are not understood. We have shown previously that luminal epithelial cells can be polarized when cultured within a reconstituted basement membrane gel. We reasoned that such cues in vivo may be given by myoepithelial cells. Accordingly, we used an assay where luminal epithelial cells are incorrectly polarized to test this hypothesis. We show that culturing human primary luminal epithelial cells within collagen-I gels leads to formation of structures with no lumina and with reverse polarity as judged by dual stainings for sialomucin, epithelial specific antigen or occludin. No basement membrane is deposited, and {beta}4-integrin staining is negative. Addition of purified human myoepithelial cells isolated from normal glands corrects the inverse polarity, and leads to formation of double-layered acini with central lumina. Among the laminins present in the human breast basement membrane (laminin-1, -5 and -10/11), laminin-1 was unique in its ability to substitute for myoepithelial cells in polarity reversal. Myoepithelial cells were purified also from four different breast cancer sources including a biphasic cell line. Three out of four samples either totally lacked the ability to interact with luminal epithelial cells, or conveyed only correction of polarity in a fraction of acini. This behavior was directly related to the ability of the tumor myoepithelial cells to produce {alpha}-1 chain of laminin. In vivo, breast carcinomas were either negative for laminin-1 (7/12 biopsies) or showed a focal, fragmented deposition of a less intensely stained basement membrane (5/12 biopsies). Dual staining with myoepithelial markers revealed that tumorassociated myoepithelial cells were either negative or weakly positive for expression of laminin-1, establishing a strong correlation between loss of laminin-1 and breast cancer. We conclude that the double-layered breast acinus may be

  20. Recurrent read-through fusion transcripts in breast cancer.

    PubMed

    Varley, Katherine E; Gertz, Jason; Roberts, Brian S; Davis, Nicholas S; Bowling, Kevin M; Kirby, Marie K; Nesmith, Amy S; Oliver, Patsy G; Grizzle, William E; Forero, Andres; Buchsbaum, Donald J; LoBuglio, Albert F; Myers, Richard M

    2014-07-01

    Read-through fusion transcripts that result from the splicing of two adjacent genes in the same coding orientation are a recently discovered type of chimeric RNA. We sought to determine if read-through fusion transcripts exist in breast cancer. We performed paired-end RNA-seq of 168 breast samples, including 28 breast cancer cell lines, 42 triple negative breast cancer primary tumors, 42 estrogen receptor positive (ER+) breast cancer primary tumors, and 56 non-malignant breast tissue samples. We analyzed the sequencing data to identify breast cancer associated read-through fusion transcripts. We discovered two recurrent read-through fusion transcripts that were identified in breast cancer cell lines, confirmed across breast cancer primary tumors, and were not detected in normal tissues (SCNN1A-TNFRSF1A and CTSD-IFITM10). Both fusion transcripts use canonical splice sites to join the last splice donor of the 5' gene to the first splice acceptor of the 3' gene, creating an in-frame fusion transcript. Western blots indicated that the fusion transcripts are translated into fusion proteins in breast cancer cells. Custom small interfering RNAs targeting the CTSD-IFITM10 fusion junction reduced expression of the fusion transcript and reduced breast cancer cell proliferation. Read-through fusion transcripts between adjacent genes with different biochemical functions represent a new type of recurrent molecular defect in breast cancer that warrant further investigation as potential biomarkers and therapeutic targets. Both breast cancer associated fusion transcripts identified in this study involve membrane proteins (SCNN1A-TNFRSF1A and CTSD-IFITM10), which raises the possibility that they could be breast cancer-specific cell surface markers. PMID:24929677

  1. Comparison of normal tissue pharmacokinetics with {sup 111}In/{sup 9}Y monoclonal antibody m170 for breast and prostate cancer

    SciTech Connect

    Lehmann, Joerg; O'Donnell, Robert T.; Richman, Carol M. . E-mail: sjdenardo@ucdavis.edu

    2006-11-15

    Purpose: Radioactivity deposition in normal tissues limits the dose deliverable by radiopharmaceuticals (RP) in radioimmunotherapy (RIT). This study investigated the absorbed radiation dose in normal tissues for prostate cancer patients in comparison to breast cancer patients for 2 RPs using the monoclonal antibody (MAb) m170. Methods and Materials: {sup 111}In-DOTA-glycylglycylglycyl-L-p-isothiocyanatophenylalanine amide (GGGF)-m170 and {sup 111}In-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) 2-iminothiolane (2IT)-m170, representing the same MAb and chelate with and without a cleavable linkage, were studied in 13 breast cancer and 26 prostate cancer patients. Dosimetry for {sup 9}Y was calculated using {sup 111}In MAb pharmacokinetics from the initial imaging study for each patient, using reference man- and patient-specific masses. Results: The reference man-specific radiation doses (cGy/MBq) were not significantly different for the breast and the prostate cancer patients for both RPs in all but one tissue-RP combination (liver, DOTA-2IT). The patient-specific doses had differences between the groups most of which can be related to weight differences. Conclusions: Similar normal tissue doses were calculated for two groups of patients having different cancers and genders. This similarity combined with continued careful analysis of the imaging data might allow the use of higher starting doses in early phase RIT studies.

  2. Effect of methionine replacement by homocystine in cultures containing both malignant rat breast carcinosarcoma (Walker-256) cells and normal adult rat liver fibroblasts.

    PubMed

    Halpern, B C; Ezzell, R; Hardy, D N; Clark, B R; Ashe, H; Halpern, R M; Smith, R A

    1975-01-01

    When malignant W-256 rat breast carcinosarcoma cells are mixed with an equal number of normal adult rat liver fibroblasts and allowed to grow in a medium containing sufficient L-methionine and an excess of vitamin B12 and of folic acid, the malignant cells outgrow the normal cells, and within 2 weeks the tissue culture flasks contain only neoplastic cells. However, when ample DL-homocystine or homocysteine replaces methionine in the medium containing the same amount of vitamin B12 and folic acid, and seeded with the same type and number of malignant and normal cells, the malignant cells die and the normal cells thrive. Substantiating this conclusion are the results of injections into rats of comparable numbers of cells from each group after 3 weeks of growth in tissue culture. Fatal malignancies are produced by the homocystein-cultivated cells.

  3. Microbial dysbiosis is associated with human breast cancer.

    PubMed

    Xuan, Caiyun; Shamonki, Jaime M; Chung, Alice; Dinome, Maggie L; Chung, Maureen; Sieling, Peter A; Lee, Delphine J

    2014-01-01

    Breast cancer affects one in eight women in their lifetime. Though diet, age and genetic predisposition are established risk factors, the majority of breast cancers have unknown etiology. The human microbiota refers to the collection of microbes inhabiting the human body. Imbalance in microbial communities, or microbial dysbiosis, has been implicated in various human diseases including obesity, diabetes, and colon cancer. Therefore, we investigated the potential role of microbiota in breast cancer by next-generation sequencing using breast tumor tissue and paired normal adjacent tissue from the same patient. In a qualitative survey of the breast microbiota DNA, we found that the bacterium Methylobacterium radiotolerans is relatively enriched in tumor tissue, while the bacterium Sphingomonas yanoikuyae is relatively enriched in paired normal tissue. The relative abundances of these two bacterial species were inversely correlated in paired normal breast tissue but not in tumor tissue, indicating that dysbiosis is associated with breast cancer. Furthermore, the total bacterial DNA load was reduced in tumor versus paired normal and healthy breast tissue as determined by quantitative PCR. Interestingly, bacterial DNA load correlated inversely with advanced disease, a finding that could have broad implications in diagnosis and staging of breast cancer. Lastly, we observed lower basal levels of antibacterial response gene expression in tumor versus healthy breast tissue. Taken together, these data indicate that microbial DNA is present in the breast and that bacteria or their components may influence the local immune microenvironment. Our findings suggest a previously unrecognized link between dysbiosis and breast cancer which has potential diagnostic and therapeutic implications. PMID:24421902

  4. Rapid Discrimination of Malignant Breast Lesions from Normal Tissues Utilizing Raman Spectroscopy System: A Systematic Review and Meta-Analysis of In Vitro Studies

    PubMed Central

    Jia, Hongyuan; Wei, Zhigong; Xiao, Yue; Xu, Jing

    2016-01-01

    Purpose The aim of this study is to evaluate the diagnostic accuracy of Raman spectroscopy system in the detection of malignant breast lesions through a systemic review and meta-analysis of published studies. Methods We conducted a comprehensive literature search of PubMed and Embase from 2000 to June 2015. Published studies that evaluated the diagnostic performance of Raman spectroscopy in distinguishing malignant breast lesions from benign lesions and normal tissues were included in our study. The pooled sensitivity, specificity, diagnostic odds ratio, and the area under the curve of summary receiver-operating characteristic curves was derived. A Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies guidelines was used to assess the quality of included studies. Results The initial search produced a total of 157 articles after removing duplicates. Nine studies (8 in vitro and 1 in vivo) were eligible in this meta-analysis. We analyzed the eight in vitro studies with 1756 lesions, the pooled sensitivity and specificity of Raman spectroscopy system for the diagnosis of malignant breast lesions were 0.92 (95% CI 0.86–0.96) and 0.97 (97% CI 0.93–0.98), respectively. Diagnostic odds ratio was 266.70 (95% CI 89.38–795.79), and the area under the curve of summary receiver-operating characteristic curves was 0.98 (95% CI 0.97–0.99). Significant heterogeneity was found between studies. There was no evidence of considerable publication bias. Conclusions Raman spectroscopy system is an optical diagnostic technology with great value for detecting malignant breast lesions. At the same time, it has advantages of being non-invasive, real-time, and easy to use. Thus it deserves to be further explored for intra-operatory breast tumor margin detection. PMID:27459193

  5. Heterogeneous Distribution of Fetal Microchimerism in Local Breast Cancer Environment

    PubMed Central

    Nemescu, Dragos; Ursu, Ramona Gabriela; Nemescu, Elena Roxana; Negura, Lucian

    2016-01-01

    Fetal cells enter maternal circulation during pregnancy and persist in the woman’s body for decades, achieving a form of physiological microchimerism. These cells were also evidenced in tumors. We investigated the frequency and concentration of fetal microchimerism in the local breast cancer environment. From 19 patients with confirmed breast neoplasia, after breast surgical resection, we collected three fresh specimens from the tumor core, breast tissue at tumor periphery, and adjacent normal breast tissue. The presence of male DNA was analyzed with a quantitative PCR assay for the sex determining region gene (SRY) gene. In the group of women who had given birth to at least one son, we detected fetal microchimerism in 100% of samples from tumors and their periphery and in 64% (9 of 14) of those from normal breast tissue. The tissues from the tumor and its periphery carry a significantly increased number of SRY copies compared to its neighboring common breast tissue (p = 0.005). The median of the normalized SRY-signal was about 77 (range, 3.2–21467) and 14-fold (range, 1.3–2690) greater in the tumor and respectively in the periphery than in the normal breast tissue. In addition, the relative expression of the SRY gene had a median 5.5 times larger in the tumor than in its periphery (range, 1.1–389.4). We found a heterogeneous distribution of fetal microchimerism in breast cancer environment. In women with sons, breast neoplasia harbors male cells at significantly higher levels than in peripheral and normal breast tissue. PMID:26808509

  6. Adjacent segment disease.

    PubMed

    Virk, Sohrab S; Niedermeier, Steven; Yu, Elizabeth; Khan, Safdar N

    2014-08-01

    EDUCATIONAL OBJECTIVES As a result of reading this article, physicians should be able to: 1. Understand the forces that predispose adjacent cervical segments to degeneration. 2. Understand the challenges of radiographic evaluation in the diagnosis of cervical and lumbar adjacent segment disease. 3. Describe the changes in biomechanical forces applied to adjacent segments of lumbar vertebrae with fusion. 4. Know the risk factors for adjacent segment disease in spinal fusion. Adjacent segment disease (ASD) is a broad term encompassing many complications of spinal fusion, including listhesis, instability, herniated nucleus pulposus, stenosis, hypertrophic facet arthritis, scoliosis, and vertebral compression fracture. The area of the cervical spine where most fusions occur (C3-C7) is adjacent to a highly mobile upper cervical region, and this contributes to the biomechanical stress put on the adjacent cervical segments postfusion. Studies have shown that after fusion surgery, there is increased load on adjacent segments. Definitive treatment of ASD is a topic of continuing research, but in general, treatment choices are dictated by patient age and degree of debilitation. Investigators have also studied the risk factors associated with spinal fusion that may predispose certain patients to ASD postfusion, and these data are invaluable for properly counseling patients considering spinal fusion surgery. Biomechanical studies have confirmed the added stress on adjacent segments in the cervical and lumbar spine. The diagnosis of cervical ASD is complicated given the imprecise correlation of radiographic and clinical findings. Although radiological and clinical diagnoses do not always correlate, radiographs and clinical examination dictate how a patient with prolonged pain is treated. Options for both cervical and lumbar spine ASD include fusion and/or decompression. Current studies are encouraging regarding the adoption of arthroplasty in spinal surgery, but more long

  7. Amount of stroma is associated with mammographic density and stromal expression of oestrogen receptor in normal breast tissues.

    PubMed

    Gabrielson, Marike; Chiesa, Flaminia; Paulsson, Janna; Strell, Carina; Behmer, Catharina; Rönnow, Katarina; Czene, Kamila; Östman, Arne; Hall, Per

    2016-07-01

    Following female sex and age, mammographic density is considered one of the strongest risk factors for breast cancer. Despite the association between mammographic density and breast cancer risk, little is known about the underlying histology and biological basis of breast density. To better understand the mechanisms behind mammographic density we assessed morphology, proliferation and hormone receptor status in relation to mammographic density in breast tissues from healthy women. Tissues were obtained from 2012-2013 by ultrasound-guided core needle biopsy from 160 women as part of the Karma (Karolinska mammography project for risk prediction for breast cancer) project. Mammograms were collected through routine mammography screening and mammographic density was calculated using STRATUS. The histological composition, epithelial and stromal proliferation status and hormone receptor status were assessed through immunohistochemical staining. Higher mammographic density was significantly associated with a greater proportion of stromal and epithelial tissue and a lower proportion of adipose tissue. Epithelial expression levels of Ki-67, oestrogen receptor (ER) and progesterone receptor (PR) were not associated with mammographic density. Epithelial Ki-67 was associated with a greater proportion of epithelial tissue, and epithelial PR was associated with a greater proportion of stromal and a lower proportion of adipose tissue. Epithelial ER was not associated with any tissues. In contrast, expression of ER in the stroma was significantly associated with a greater proportion of stroma, and negatively associated with the amount of adipose tissue. High mammographic density is associated with higher amount of stroma and epithelium and less amount of fat, but is not associated with a change in epithelial proliferation or receptor status. Increased expressions of both epithelial PR and stromal ER are associated with a greater proportion of stroma, suggesting hormonal involvement

  8. Comparative regulation of gene expression by 1,25-dihydroxyvitamin D3 in cells derived from normal mammary tissue and breast cancer

    PubMed Central

    Beaudin, Sarah G; Robilotto, Samantha; Welsh, JoEllen

    2016-01-01

    Previous genomic profiling of immortalized, non-tumorigenic human breast epithelial cells identified a set of 1,25-dihydroxyvitamin D3 (1,25D) regulated genes with potential relevance to breast cancer prevention. In this report, we characterized the effect of 1,25D on a subset of these genes in six cell lines derived from mammary tissue and breast cancers. Non-tumorigenic cell lines included hTERT-HME1, HME and MCF10A cells which are often used to model normal breast epithelial cells. Breast cancer cell lines included MCF7 cells (a model of early stage, estrogen-dependent disease), DCIS.com cells (a derivative of MCF10A cells that models in situ breast cancer) and Hs578T cells (a model of metastatic disease). All of these cell lines express the vitamin D receptor (VDR) and exhibit anti-cancer responses to 1,25D such as changes in proliferation, apoptosis, metabolism, or invasion. Our comparative data demonstrate highly variable responses to 1,25D (100nM, 24h) between the cell lines. In both hTERT-HME1 and HME cell lines, CYP24A1, SLC1A1 and ITGB3 were up-regulated whereas KDR, GLUL and BIRC3 were down-regulated in response to 1,25D. In contrast, no changes in SLC1A1, ITGB3 or GLUL expression were detected in 1,25D treated MCF10A cells although KDR and BIRC3 were down-regulated by 1,25D. The effects of 1,25D on these genes in the breast cancer cell lines were blunted, with the DCIS.com cells exhibiting the most similar responses to the immortalized hTERT-HME1 and HME cells. The differences in cellular responses were not due to general impairment in VDR function as robust CYP24A1 induction was observed in all cell lines. Thus, our data indicate that the genomic changes induced by 1,25D are highly cell-type specific even in model cell lines derived from the same tissue. The implication of these findings is that genomic responses to changes in vitamin D status in vivo are likely to be distinct from individual to individual, particularly in neoplastic tissue. PMID

  9. NASA SMART Probe: Breast Cancer Application

    NASA Technical Reports Server (NTRS)

    Mah, Robert W.; Norvig, Peter (Technical Monitor)

    2000-01-01

    There is evidence in breast cancer and other malignancies that the physiologic environment within a tumor correlates with clinical outcome. We are developing a unique percutaneous Smart Probe to be used at the time of needle biopsy of the breast. The Smart Probe will simultaneously measure multiple physiologic parameters within a breast tumor. Direct and indirect measurements of tissue oxygen levels, blood flow, pH, and tissue fluid pressure will be analyzed in real-time. These parameters will be interpreted individually and collectively by innovative neural network techniques using advanced intelligent software. The goals are 1) develop a pecutaneous Smart Probe with multiple sensor modalities and applying advanced Information Technologies to provide real time diagnostic information of the tissue at tip of the probe, 2) test the percutaneous Smart Probe in women with benign and malignant breast masses who will be undergoing surgical biopsy, 3) correlate probe sensor data with benign and malignant status of breast masses, 4) determine whether the probe can detect physiologic differences within a breast tumor, and its margins, and in adjacent normal breast tissue, 5) correlate probe sensor data with known prognostic factors for breast caner, including tumor size, tumor grade, axillary lymph node metastases, estrogen receptor and progesterone receptor status.

  10. The role of tumor-associated macrophages in breast carcinoma invasion and metastasis.

    PubMed

    Yang, Ju; Li, Xiaojing; Liu, Xiuping; Liu, Yongjuan

    2015-01-01

    The main purpose of this study was to investigate the infiltration of tumor-associated macrophages (TAMs) in normal and malignant breast tissue and the draining lymph nodes, and to explore its effect on breast cancer invasion and metastasis. The infiltration densities of TAMs was observed using immunohistochemical staining of CD68 in 100 cases of breast cancer specimens and its paired adjacent non-cancer breast tissues and draining lymph modes, and then to evaluate the relation of TAMs to various clinicopathological features including patients prognosis in breast carcinoma. We observed the infiltration densities of TAMs were significantly higher in breast carcinoma tissue than in adjacent normal tissue and significantly higher in much larger size and higher stage cases. Furthermore, infiltration densities of TAMs have negative correlation with the 5-year survival rates of breast cancer patients. But in matched lymph-nodes, the infiltration densities of TAMs were significantly lower in cancerous metastatic lymph-node samples than in non-metastatic one. Therefore, our data suggests that TAMs infiltration in primary tumor promote invasion and lymphatic metastasis of breast cancer and have negative correlation with patients prognosis in breast cancer, but in lymph-node TAMs may play another role and need further study in the future.

  11. Breast cancer 1 (BRCA1)-deficient embryos develop normally but are more susceptible to ethanol-initiated DNA damage and embryopathies.

    PubMed

    Shapiro, Aaron M; Miller-Pinsler, Lutfiya; Wells, Peter G

    2016-04-01

    The breast cancer 1 (brca1) gene is associated with breast and ovarian cancers, and heterozygous (+/-) brca1 knockout progeny develop normally, suggesting a negligible developmental impact. However, our results show BRCA1 plays a broader biological role in protecting the embryo from oxidative stress. Sox2-promoted Cre-expressing hemizygous males were mated with floxed brca1 females, and gestational day 8 +/- brca1 conditional knockout embryos with a 28% reduction in protein expression were exposed in culture to the reactive oxygen species (ROS)-initiating drug ethanol (EtOH). Untreated +/- brca1-deficient embryos developed normally, but when exposed to EtOH exhibited increased levels of oxidatively damaged DNA, measured as 8-oxo-2'-deoxyguanosine, γH2AX, which is a marker of DNA double strand breaks that can result from 8-oxo-2'-deoxyguanosine, formation, and embryopathies at EtOH concentrations that did not affect their brca1-normal littermates. These results reveal that even modest BRCA1 deficiencies render the embryo more susceptible to drug-enhanced ROS formation, and corroborate a role for DNA oxidation in the mechanism of EtOH teratogenesis. PMID:26629949

  12. Breast cancer 1 (BRCA1)-deficient embryos develop normally but are more susceptible to ethanol-initiated DNA damage and embryopathies☆

    PubMed Central

    Shapiro, Aaron M.; Miller-Pinsler, Lutfiya; Wells, Peter G.

    2015-01-01

    The breast cancer 1 (brca1) gene is associated with breast and ovarian cancers, and heterozygous (+/−) brca1 knockout progeny develop normally, suggesting a negligible developmental impact. However, our results show BRCA1 plays a broader biological role in protecting the embryo from oxidative stress. Sox2-promoted Cre-expressing hemizygous males were mated with floxed brca1 females, and gestational day 8 +/− brca1 conditional knockout embryos with a 28% reduction in protein expression were exposed in culture to the reactive oxygen species (ROS)-initiating drug ethanol (EtOH). Untreated +/− brca1-deficient embryos developed normally, but when exposed to EtOH exhibited increased levels of oxidatively damaged DNA, measured as 8-oxo-2'-deoxyguanosine, γH2AX, which is a marker of DNA double strand breaks that can result from 8-oxo-2'-deoxyguanosine, formation, and embryopathies at EtOH concentrations that did not affect their brca1-normal littermates. These results reveal that even modest BRCA1 deficiencies render the embryo more susceptible to drug-enhanced ROS formation, and corroborate a role for DNA oxidation in the mechanism of EtOH teratogenesis. PMID:26629949

  13. Differential regulation of cell proliferation and protease secretion by epidermal growth factor and amphiregulin in tumoral versus normal breast epithelial cells

    PubMed Central

    Silvy, M; Giusti, C; Martin, P-M; Berthois, Y

    2001-01-01

    Amphiregulin (AR) is a heparin-binding epidermal growth factor (EGF)-related peptide that seems to play an important role in mammary epithelial cell growth regulation. We have investigated the regulation of AR-gene expression and -protein secretion by EGF in normal breast epithelial cells (HMECs), as well as in the tumoral breast epithelial cell lines MCF-7 and MDA-MB231. EGF induced a dose-dependent increase of AR mRNA level in both normal and tumoral cells. Thus, 10−8M EGF stimulated AR expression in HMECs to 140–300% of control. A similar EGF concentration increased AR mRNA level to 550% and 980% of control in MCF-7 and MDA-MB231 cells, respectively. This was accompanied by an accumulation of AR into conditioned culture media. However, HMECs secreted in response to EGF, 5–10 fold more AR than tumour cells. Furthermore, the potential participation of AR in the regulation of the plasminogen activator (PA)/plasmin system was investigated. Whereas HMEC-proliferation was stimulated by AR, the levels of secreted urokinase-type plasminogen activator (uPA) and type-1 plasminogen activator inhibitor (PAi-1) remained unaffected. Conversely, AR failed to regulate the proliferation of tumoral cell lines but induced an accumulation of uPA and PAi-1 into culture media. This was accompanied by an increase of the number of tumoral cells that invaded matrigel in vitro. Moreover, the presence of a neutralizing anti-uPA receptor antibody reversed the increased invasiveness of MDA-MB231 cells induced by AR. These data reveal differential behaviour of normal versus tumoral breast epithelial cells in regard to the action of AR and demonstrate that, in a number of cases, AR might play a significant role in tumour progression through the regulation of the PA/plasmin system. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11286474

  14. A study of the effect of formalin preservation on normal and cancerous breast tissues using small angle X-ray scattering (SAXS)

    NASA Astrophysics Data System (ADS)

    Changizi, V.; Wilkinson, S.; Hall, C. J.; Grossmann, G.

    2006-09-01

    Small angle X-ray scattering (SAXS) has the ability to provide information on a molecular and supra-molecular scale from biological tissue specimens. It has been postulated that this information will be useful in providing histopathological diagnoses for certain diseases of the breast. In this category, we include cancer, a major health problem for a number of populations around the world. So far studies in our group have been made using flash-frozen tissue samples. This limits the range and ease of use of the technique. If we were able to obtain the same information from preserved tissues then a more extensive use of SAXS diagnosis would be possible. Here we report on the first investigations into this possibility. In the research reported in this paper, 84 human breast biopsies including cancer and normal tissues were obtained from human patients. Small angle scatter data were collected at station 2.1 of the SRS at the Daresbury Laboratory, UK using a beam size of 0.25 mm 2 at the sample and a wavelength of 1.54 Å. The sample to detector distance was 2000 mm. The results verify that there is a quantifiable difference between the scatter curves from flash-frozen cancer and normal breast tissue in the range of scatter vector Q between 0.4 and 0.7 nm -1. After preserving the tissues in formalin, the difference between the normal and cancerous tissues is less marked. The preservation of the tissue in formalin can essentially mask the effects that disease would have on the tissue supra-molecular structure rendering the preserved specimens of less useful for this histopathology technique.

  15. Immunohistochemical analysis of MUC5B apomucin expression in breast cancer and non-malignant breast tissues.

    PubMed

    Sóñora, Cecilia; Mazal, Daniel; Berois, Nora; Buisine, Marie-Pierre; Ubillos, Luis; Varangot, Mario; Barrios, Enrique; Carzoglio, Julio; Aubert, Jean-Pierre; Osinaga, Eduardo

    2006-03-01

    A deregulation of several MUC genes (MUC1, MUC2, MUC3, MUC5AC, and MUC6) was previously demonstrated in breast carcinomas. Considering that recently we found the "non-mammary" MUC5B mRNA in primary breast tumors (Berois et al. 2003), we undertook the present study to evaluate the expression profile of MUC5B protein product in breast tissues, using LUM5B-2 antisera raised against sequences within the non-glycosylated regions of this apomucin. Expression of MUC5B by breast cancer cells was confirmed by immunocytochemistry, in situ hybridization, and Western blot on MCF-7 cancer cells. Using an immunohistochemical procedure, MUC5B apomucin was detected in 34/42 (81%) primary breast tumors, in 13/14 (92.8%) samples of non-malignant breast diseases, in 8/19 (42.1%) samples of normal-appearing breast epithelia adjacent to cancer, and in 0/5 normal control breast samples. The staining pattern of MUC5B was very different when comparing breast cancer cells (cytoplasmic) and non-malignant breast cells (predominantly apical and in the secretory material). We analyzed MUC5B mRNA expression using RT-PCR in bone marrow aspirates from 22/42 patients with breast cancer to compare with MUC5B protein expression in the primary tumors. Good correlation was observed because the six MUC5B-positive bone marrow samples also displayed MUC5B expression in the tumor. Our results show, for the first time at the protein level, that MUC5B apomucin is upregulated in breast cancer. Its characterization could provide new insights about the glycobiology of breast cancer cells. PMID:16148312

  16. Long-term exposure of MCF-12A normal human breast epithelial cells to ethanol induces epithelial mesenchymal transition and oncogenic features

    PubMed Central

    GELFAND, ROBERT; VERNET, DOLORES; BRUHN, KEVIN; VADGAMA, JAYDUTT; GONZALEZ-CADAVID, NESTOR F.

    2016-01-01

    Alcoholism is associated with breast cancer incidence and progression, and moderate chronic consumption of ethanol is a risk factor. The mechanisms involved in alcohol's oncogenic effects are unknown, but it has been speculated that they may be mediated by acetaldehyde. We used the immortalized normal human epithelial breast cell line MCF-12A to determine whether short- or long-term exposure to ethanol or to acetaldehyde, using in vivo compatible ethanol concentrations, induces their oncogenic transformation and/or the acquisition of epithelial mesenchymal transition (EMT). Cultures of MCF-12A cells were incubated with 25 mM ethanol or 2.5 mM acetaldehyde for 1 week, or with lower concentrations (1.0–2.5 mM for ethanol, 1.0 mM for acetaldehyde) for 4 weeks. In the 4-week incubation, cells were also tested for anchorage-independence, including isolation of soft agar selected cells (SASC) from the 2.5 mM ethanol incubations. Cells were analyzed by immunocytofluorescence, flow cytometry, western blotting, DNA microarrays, RT/PCR, and assays for miRs. We found that short-term exposure to ethanol, but not, in general, to acetaldehyde, was associated with transcriptional upregulation of the metallothionein family genes, alcohol metabolism genes, and genes suggesting the initiation of EMT, but without related phenotypic changes. Long-term exposure to the lower concentrations of ethanol or acetaldehyde induced frank EMT changes in the monolayer cultures and in SASC as demonstrated by changes in cellular phenotype, mRNA expression, and microRNA expression. This suggests that low concentrations of ethanol, with little or no mediation by acetaldehyde, induce EMT and some traits of oncogenic transformation such as anchorage-independence in normal breast epithelial cells. PMID:27035792

  17. Abortion, Miscarriage, and Breast Cancer Risk

    MedlinePlus

    ... Cancers Breast Cancer Screening Research Abortion, Miscarriage, and Breast Cancer Risk A woman’s hormone levels normally change throughout ... the development of breast cancer. Important Information about Breast Cancer Risk Factors At present, the factors known to ...

  18. A functional single nucleotide polymorphism of SET8 is prognostic for breast cancer.

    PubMed

    Liu, Ben; Zhang, Xining; Song, Fengju; Liu, Qun; Dai, Hongji; Zheng, Hong; Cui, Ping; Zhang, Lina; Zhang, Wei; Chen, Kexin

    2016-06-01

    A single-nucleotide polymorphism (SNP) locus rs16917496 (T > C) within the 3'-untranslated region (3'-UTR) of SET8 was associated with susceptibility in several malignancies including breast cancer. To further elucidate the prognostic relevance of this SNP in breast cancer, we conducted a clinical study as well as SET8 expression analysis in a cohort of 1,190 breast cancer patients. We demonstrated the expression levels of SET8 in TT genotype were higher than in CC genotypes, and high levels of SET8 were associated with poor survival. SET8 expression was significantly higher in breast tumor tissue than in paired adjacent normal tissue. In addition, survival analysis in 315 patients showed SNP rs16917496 was an independent prognostic factor of breast cancer outcome with TT genotype associated with poor survival compared with CC/CT genotypes. Thus, this SNP may serve as a genetic prognostic factor and a treatment target for breast cancer. Future studies are warranted.

  19. Effect of different cytokines on mammaglobin and maspin gene expression in normal leukocytes: possible relevance to the assays for the detection of micrometastatic breast cancer

    PubMed Central

    Ballestrero, A; Garuti, A; Bertolotto, M; Rocco, I; Boy, D; Nencioni, A; Ottonello, L; Patrone, F

    2005-01-01

    In cancer patients, the ability to detect disseminated tumour cells in peripheral blood or bone marrow could improve prognosis and consent both early detection of metastatic disease and monitoring of the efficacy of systemic therapy. These objectives remain elusive mainly due to the lack of specific genetic markers for solid tumours. The use of surrogate tissue-specific markers can reduce the specificity of the assays and give rise to a clinically unacceptable false-positive rate. Mammaglobin (MAM) and maspin are two putative breast tissue-specific markers frequently used for detection of occult tumour cells in the peripheral blood, bone marrow and lymph nodes of breast cancer patients. In this study, it was evaluated whether MAM and maspin gene expression may be induced in the normal blood and bone marrow cells exposed to a panel of cytokines, including chemotactic factors (C5a, interleukin (IL)-8), LPS, proinflammatory cytokines (TNF-α, IL-1β) and growth factors (IL-3, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor). The experimental data show that all cytokines included in the panel, except for IL-8, were able to induce maspin expression; on the contrary, MAM gene was never induced. These results suggest that MAM is more specific than maspin and that the possible interference of cytokines should be taken into account in interpreting molecular assays for detection of isolated tumour cells. PMID:15841077

  20. In vitro synthesis of primary specific anti-breast cancer antibodies by normal human peripheral blood mononuclear cells

    PubMed Central

    Norkina, Oxana; Lum, Lawrence G.

    2013-01-01

    In this study, we developed a unique in vitro model to mimic the endogenous tumor microenvironment to understand the effect of immunotherapy with activated T-cells (ATC) armed with anti-CD3 × anti-Her2 bispecific antibody (aATC) on antibody response by naive immune cells. This model contained a co-culture of naïve peripheral blood mononuclear cells (PBMC), breast cancer cells (SK-BR-3), ATC or aATC and CpG ODNs. Culture supernatants were tested at various time points for anti-SK-BR-3 antibodies by ELISA, Western blot and flow cytometry. PBMC cocultured with non-irradiated aATC or irradiated (*) aATC showed significant increases in anti-tumor antibody production at day 14 (P < 0.0001) in the presence of CpG-ODN compared to unstimulated PBMC cultures (n = 9). Antibody specificity was confirmed by ELISA, Western blot and flow cytometry. Co-cultures containing *aATC and CpG showed significantly enhanced levels of IgG2 (P < 0.001) and cytokines that promote IgG2 synthesis including IL-13 (P < 0.02), IFNγ (P < 0.01) and GM-CSF (P < 0.05) compared to unstimulated PBMC control (n = 3). We show that aATC targeting and lysis of tumor cells induces an anti-tumor antibody response in our in vitro model. This model provides a unique opportunity to evaluate the interactions of T-cells, B-cells, and antigen-presenting cells leading to specific anti-tumor antibody responses. PMID:21713642

  1. [Effects of tree diameter at breast height and soil moisture on transpiration of Schima superba based on sap flow pattern and normalization].

    PubMed

    Mei, Ting-ting; Zhao, Ping; Wang, Quan; Cai, Xi-an; Yu, Meng-hao; Zhu, Li-wei; Zou, Lü-liu; Zeng, Xiao-ping

    2010-10-01

    The eigenvalues of continuous sap flow pattern, i. e. , skewness and kurtosis, were used to investigate the water usage of Schima superba with different diameter at breast height (DBH), and the method of normalization was firstly applied to eliminate the effects of strong affecting factor (photosynthetic active radiation, PAR) to explore the possible relationship between weak affecting factor (soil moisture) and sap flow. Generally, the trees with larger DBH had smaller skewness of sap flux density and later-appeared but larger peak values, suggesting that much more water was transpired, and the larger trees showed smaller skewness and later-appeared larger peak values in wet season than in dry season, suggesting that more water was transpired in wet season. On the other hand, smaller trees had lesser differences in the skewness between dry and wet seasons, suggesting that there was no significant difference in the transpiration between the two seasons. The relationship between individual tree's transpiration and soil moisture was significant and positive after the two parameters being normalized with PAR peak values. When the soil moisture content was higher, the transpiration of the trees with larger DBH was steadily increasing with soil moisture, while that of the trees with moderate or smaller DBH had opposite trend, presumably due to their transpiration and water absorption were approached to the limit.

  2. Correlating two-photon excited fluorescence imaging of breast cancer cellular redox state with seahorse flux analysis of normalized cellular oxygen consumption

    NASA Astrophysics Data System (ADS)

    Hou, Jue; Wright, Heather J.; Chan, Nicole; Tran, Richard; Razorenova, Olga V.; Potma, Eric O.; Tromberg, Bruce J.

    2016-06-01

    Two-photon excited fluorescence (TPEF) imaging of the cellular cofactors nicotinamide adenine dinucleotide and oxidized flavin adenine dinucleotide is widely used to measure cellular metabolism, both in normal and pathological cells and tissues. When dual-wavelength excitation is used, ratiometric TPEF imaging of the intrinsic cofactor fluorescence provides a metabolic index of cells-the "optical redox ratio" (ORR). With increased interest in understanding and controlling cellular metabolism in cancer, there is a need to evaluate the performance of ORR in malignant cells. We compare TPEF metabolic imaging with seahorse flux analysis of cellular oxygen consumption in two different breast cancer cell lines (MCF-7 and MDA-MB-231). We monitor metabolic index in living cells under both normal culture conditions and, for MCF-7, in response to cell respiration inhibitors and uncouplers. We observe a significant correlation between the TPEF-derived ORR and the flux analyzer measurements (R=0.7901, p<0.001). Our results confirm that the ORR is a valid dynamic index of cell metabolism under a range of oxygen consumption conditions relevant for cancer imaging.

  3. Dicer expression in estrogen receptor-positive versus triple-negative breast cancer: an antibody comparison.

    PubMed

    Spoelstra, Nicole S; Cittelly, Diana M; Christenson, Jessica L; Gordon, Michael A; Elias, Anthony; Jedlicka, Paul; Richer, Jennifer K

    2016-10-01

    Dicer is an RNase III enzyme responsible for cleaving double-stranded RNAs into small interfering RNAs and microRNAs, which either target messenger RNA transcripts for degradation or inhibit translation. Dicer protein levels have been examined in breast cancer with contradictory results. Our goal was to resolve whether Dicer levels differ in breast cancer versus normal breast epithelium and between estrogen receptor-α-positive (ER+) or estrogen receptor-α-negative (ER-) primary breast cancers. We compared 3 different Dicer antibodies: Abcam 4A6, Abcam ab5818, and Sigma HPA000694, using immunohistochemistry and Western blot analyses. All 3 Dicer antibodies detected higher levels of Dicer in ER+ breast cancer cell lines versus ER-, and all 3 recognized exogenous overexpressed Dicer. In clinical specimens, all 3 antibodies detected higher Dicer in ER+ breast cancers versus triple-negative breast cancer (TNBC) but had very different staining patterns by immunohistochemistry on the same tumor samples. Using the optimal antibody, ab5818, selected for its sensitivity and specificity, Dicer protein expression was significantly higher in ER+ versus TNBC clinical specimens of primary tumor (P<.0001, unpaired t test). Dicer was also significantly higher in adjacent normal breast epithelium versus TNBC (P<.0001, paired t test; n=18 pairs). Differences in antibody performance may explain contrasting results observed in the literature regarding Dicer protein in breast cancer. If Dicer becomes more clinically relevant as a prognostic indicator, further antibody optimization and standardization will be critical. PMID:27260947

  4. The specific role of pRb in p16 (INK4A) -mediated arrest of normal and malignant human breast cells.

    PubMed

    Bazarov, Alexey V; Lee, Won Jae; Bazarov, Irina; Bosire, Moses; Hines, William C; Stankovich, Basha; Chicas, Agustin; Lowe, Scott W; Yaswen, Paul

    2012-03-01

    RB family proteins pRb, p107 and p130 have similar structures and overlapping functions, enabling cell cycle arrest and cellular senescence. pRb, but not p107 or p130, is frequently mutated in human malignancies. In human fibroblasts acutely exposed to oncogenic ras, pRb has a specific role in suppressing DNA replication, and p107 or p130 cannot compensate for the loss of this function; however, a second p53/p21-dependent checkpoint prevents escape from growth arrest. This model of oncogene-induced senescence requires the additional loss of p53/p21 to explain selection for preferential loss of pRb function in human malignancies. We asked whether similar rules apply to the role of pRb in growth arrest of human epithelial cells, the source of most cancers. In two malignant human breast cancer cell lines, we found that individual RB family proteins were sufficient for the establishment of p16-initiated senescence, and that growth arrest in G 1 was not dependent on the presence of functional pRb or p53. However, senescence induction by endogenous p16 was delayed in primary normal human mammary epithelial cells with reduced pRb but not with reduced p107 or p130. Thus, under these circumstances, despite the presence of functional p53, p107 and p130 were unable to completely compensate for pRb in mediating senescence induction. We propose that early inactivation of pRb in pre-malignant breast cells can, by itself, extend proliferative lifespan, allowing acquisition of additional changes necessary for malignant transformation.

  5. Changes in Normal Liver and Spleen Volume after Radioembolization with {sup 90}Y-Resin Microspheres in Metastatic Breast Cancer Patients: Findings and Clinical Significance

    SciTech Connect

    Paprottka, Philipp M. Schmidt, G. P.; Trumm, C. G.; Hoffmann, R. T.; Reiser, M. F.; Jakobs, T. F.

    2011-10-15

    Purpose: In clinical trials with yttrium-90-resin-microspheres for the management of colorectal cancer liver metastases, it was observed that radioembolization might result in splenomegaly and an increase in portal vein size. Subclinical hepatitis in normal liver tissue as well as the effects of radioembolization and prior chemotherapy are suspected to be responsible for this phenomenon. The purpose of this study was to quantify the changes in liver and spleen volume and portal vein diameter after radioembolization. Methods: Twenty-seven patients with liver-dominant metastatic disease from breast cancer who had not responded to chemotherapy or had to abandon chemotherapy because of its toxic effects were evaluated. Changes in liver and spleen volume and portal vein diameter as well as liver tumor volume and diameter were quantified using computed tomography scans. Results: Radioembolization was associated with a significant mean decrease in the whole liver volume of 10.2% (median 16.7%; P = 0.0024), mainly caused by a reduction in the right lobe volume (mean 16.0%; P < 0.0001). These changes were accompanied by a significant increase in the diameter of the main portal vein (mean 6.8%; P < 0.0001) as well as splenic volume (mean 50.4%; P < 0.0001). Liver-tumor volume and diameter decreased by a median of 24 and 39.7%. Conclusions: Radioembolization is an effective treatment for tumor size reduction in patients with breast cancer liver metastases. Treatment is associated with changes of hepatic parenchymal volume, splenic volume, and portal vein size that appear not to represent clinically important sequelae in this patient cohort.

  6. Postrigor tumble marination strategies for improving color and water-holding capacity in normal and pale broiler breast fillets.

    PubMed

    Gorsuch, V; Alvarado, C Z

    2010-05-01

    Pale or pale, soft, and exudative-like meat can be caused by a decline in pH early postmortem while carcass temperatures are still high. This decrease in pH leads to protein denaturation, attributing to the pale color and poor water-holding capacity that is characteristic of this lesser quality meat. Marination with NaCl and phosphates has been shown to improve protein functionality, thereby reducing lost meat yield and improving meat quality. However, there are few studies relating marination with phosphates to improvements in pale meat. Therefore, the purpose of this experiment was to determine if meat quality improvements could be obtained in pale meat via marination with various phosphate and NaCl treatments without altering the quality and stability of normal or pale meat. The treatments used in this study were 1) sodium tripolyphosphate, an industry control; 2) a high pH phosphate (11.9); 3) a sodium tripolyphosphate and high pH mixture; 4) an agglomerated phosphate; and 5) a nonagglomerated phosphate. The marinades used in this study increased the pH, decreased the L* values of the pale fillets, and improved water-holding capacity. There were no significant differences in overall flavor preference for any of the 5 phosphate treatments. There was also no difference in oxidation or shelf-life trends in either the pale or normal fillets marinated with each of the 5 treatments. The results of this study were that marination with phosphates can be used to marinate pale meat without altering flavor, increasing the development of oxidation, or reducing shelf life. PMID:20371853

  7. Intensity modulated radiotherapy and 3D conformal radiotherapy for whole breast irradiation: a comparative dosimetric study and introduction of a novel qualitative index for plan evaluation, the normal tissue index

    PubMed Central

    Yim, Jackie; Suttie, Clare; Bromley, Regina; Morgia, Marita; Lamoury, Gillian

    2015-01-01

    Introduction We report on a retrospective dosimetric study, comparing 3D conformal radiotherapy (3DCRT) and hybrid intensity modulated radiotherapy (hIMRT). We evaluated plans based on their planning target volume coverage, dose homogeneity, dose to organs at risk (OARs) and exposure of normal tissue to radiation. The Homogeneity Index (HI) was used to assess the dose homogeneity in the target region, and we describe a new index, the normal tissue index (NTI), to assess the dose in the normal tissue inside the tangent treatment portal. Methods Plans were generated for 25 early-stage breast cancer patients, using a hIMRT technique. These were compared with the 3DCRT plans of the treatment previously received by the patients. Plan quality was evaluated using the HI, NTI and dose to OARs. Results The hIMRT technique was significantly more homogenous than the 3DCRT technique, while maintaining target coverage. The hIMRT technique was also superior at minimising the amount of tissue receiving D105% and above (P < 0.0001). The ipsilateral lung and contralateral breast maximum were significantly lower in the hIMRT plans (P < 0.05 and P < 0.005), but the 3DCRT technique achieved a lower mean heart dose in left-sided breast cancer patients (P < 0.05). Conclusion Hybrid intensity modulated radiotherapy plans achieved improved dose homogeneity compared to the 3DCRT plans and superior outcome with regard to dose to normal tissues. We propose that the addition of both HI and NTI in evaluating the quality of intensity modulated radiotherapy (IMRT) breast plans provides clinically relevant comparators which more accurately reflect the new paradigm of treatment goals and outcomes in the era of breast IMRT. PMID:26451240

  8. Intensity modulated radiotherapy and 3D conformal radiotherapy for whole breast irradiation: a comparative dosimetric study and introduction of a novel qualitative index for plan evaluation, the normal tissue index

    SciTech Connect

    Yim, Jackie; Suttie, Clare; Bromley, Regina; Morgia, Marita; Lamoury, Gillian

    2015-09-15

    We report on a retrospective dosimetric study, comparing 3D conformal radiotherapy (3DCRT) and hybrid intensity modulated radiotherapy (hIMRT). We evaluated plans based on their planning target volume coverage, dose homogeneity, dose to organs at risk (OARs) and exposure of normal tissue to radiation. The Homogeneity Index (HI) was used to assess the dose homogeneity in the target region, and we describe a new index, the normal tissue index (NTI), to assess the dose in the normal tissue inside the tangent treatment portal. Plans were generated for 25 early-stage breast cancer patients, using a hIMRT technique. These were compared with the 3DCRT plans of the treatment previously received by the patients. Plan quality was evaluated using the HI, NTI and dose to OARs. The hIMRT technique was significantly more homogenous than the 3DCRT technique, while maintaining target coverage. The hIMRT technique was also superior at minimising the amount of tissue receiving D{sub 105%} and above (P < 0.0001). The ipsilateral lung and contralateral breast maximum were significantly lower in the hIMRT plans (P < 0.05 and P < 0.005), but the 3DCRT technique achieved a lower mean heart dose in left-sided breast cancer patients (P < 0.05). Hybrid intensity modulated radiotherapy plans achieved improved dose homogeneity compared to the 3DCRT plans and superior outcome with regard to dose to normal tissues. We propose that the addition of both HI and NTI in evaluating the quality of intensity modulated radiotherapy (IMRT) breast plans provides clinically relevant comparators which more accurately reflect the new paradigm of treatment goals and outcomes in the era of breast IMRT.

  9. Overexpression of the chimeric plasmin-resistant VEGF165/VEGF183 (132-158) protein in murine breast cancer induces distinct vascular patterning adjacent to tumors and retarded tumor growth.

    PubMed

    Zhang, Hui-Yong; Fan, Bing-Lin; Wu, Xin-Sheng; Mu, Ling-Min; Wang, Wen-Feng; Zhu, Wu-Ling

    2015-02-01

    A chimeric plasmin‑resistant vascular endothelial growth factor (VEGF)165/VEGF183 (132-158) protein, named as VEGF183 (according to the nomenclature of VEGF), designed by a previous study, was demonstrated to have an enhanced affinity for the extracellular matrix (ECM) amongst other bioactivities. However, it is now accepted that mutant VEGFs frequently demonstrate different angiogenic activities and produce different vascular patterning from the parental molecule. The present study hypothesized that VEGF183, due to its enhanced binding affinity to the ECM, would exhibit a different angiogenic activity and produce a different vascular patterning compared to those of VEGF165. Murine breast cancer EMT‑6 cells were manipulated to stably overexpress VEGF165 or VEGF183. These cells were then inoculated intradermally into BALB/c mice in order to monitor the formation of vascular patterning in skin proximal to tumors. In vivo angiogenesis experiments revealed that overexpression of VEGF183 in murine breast cancer cells resulted in irregular, disorganized and dense vascular patterning as well as induced a significant inhibition of tumor growth compared with that of VEGF165. In addition, allograft tumor immunochemical assays of VEGF183‑overexpressing tumors demonstrated significantly lower vascular densities than those of VEGF165‑overexpressing tumors; however, VEGF183 tumors had a significantly enlarged vascular caliber. Conversely, cell wound healing experiments revealed that VEGF183‑overexpressing EMT‑6 cells had significantly decreased migration rates compared with those of VEGF165‑overexpressing EMT‑6 cells. In conclusion, the results of the present study supported the hypothesis that the altered ECM affinity of VEGF induced structural alterations to vasculature. In addition, these results provided a novel insight into VEGF design and indirect evidence for the function of exon 8 in VEGF. [Corrected] PMID:25373557

  10. Promoter Methylation and mRNA Expression of Response Gene to Complement 32 in Breast Carcinoma

    PubMed Central

    Eskandari-Nasab, Ebrahim; Hashemi, Mohammad; Rafighdoost, Firoozeh

    2016-01-01

    Background. Response gene to complement 32 (RGC32), induced by activation of complements, has been characterized as a cell cycle regulator; however, its role in carcinogenesis is still controversial. In the present study we compared RGC32 promoter methylation patterns and mRNA expression in breast cancerous tissues and adjacent normal tissues. Materials and Methods. Sixty-three breast cancer tissues and 63 adjacent nonneoplastic tissues were included in our study. Design. Nested methylation-specific polymerase chain reaction (Nested-MSP) and quantitative PCR (qPCR) were used to determine RGC32 promoter methylation status and its mRNA expression levels, respectively. Results. RGC32 methylation pattern was not different between breast cancerous tissue and adjacent nonneoplastic tissue (OR = 2.30, 95% CI = 0.95–5.54). However, qPCR analysis displayed higher levels of RGC32 mRNA in breast cancerous tissues than in noncancerous tissues (1.073 versus 0.959; P = 0.001), irrespective of the promoter methylation status. The expression levels and promoter methylation of RGC32 were not correlated with any of patients' clinical characteristics (P > 0.05). Conclusion. Our findings confirmed upregulation of RGC32 in breast cancerous tumors, but it was not associated with promoter methylation patterns. PMID:27118972

  11. Teaching normal birth, normally.

    PubMed

    Hotelling, Barbara A

    2009-01-01

    Teaching normal-birth Lamaze classes normally involves considering the qualities that make birth normal and structuring classes to embrace those qualities. In this column, teaching strategies are suggested for classes that unfold naturally, free from unnecessary interventions. PMID:19436595

  12. Identification and Pathway Analysis of microRNAs with No Previous Involvement in Breast Cancer

    PubMed Central

    Rebollar-Vega, Rosa; Quintanar-Jurado, Valeria; Maffuz-Aziz, Antonio; Jimenez-Sanchez, Gerardo; Bautista-Piña, Veronica; Arellano-Llamas, Rocio; Hidalgo-Miranda, Alfredo

    2012-01-01

    microRNA expression signatures can differentiate normal and breast cancer tissues and can define specific clinico-pathological phenotypes in breast tumors. In order to further evaluate the microRNA expression profile in breast cancer, we analyzed the expression of 667 microRNAs in 29 tumors and 21 adjacent normal tissues using TaqMan Low-density arrays. 130 miRNAs showed significant differential expression (adjusted P value = 0.05, Fold Change = 2) in breast tumors compared to the normal adjacent tissue. Importantly, the role of 43 of these microRNAs has not been previously reported in breast cancer, including several evolutionary conserved microRNA*, showing similar expression rates to that of their corresponding leading strand. The expression of 14 microRNAs was replicated in an independent set of 55 tumors. Bioinformatic analysis of mRNA targets of the altered miRNAs, identified oncogenes like ERBB2, YY1, several MAP kinases, and known tumor-suppressors like FOXA1 and SMAD4. Pathway analysis identified that some biological process which are important in breast carcinogenesis are affected by the altered microRNA expression, including signaling through MAP kinases and TP53 pathways, as well as biological processes like cell death and communication, focal adhesion and ERBB2-ERBB3 signaling. Our data identified the altered expression of several microRNAs whose aberrant expression might have an important impact on cancer-related cellular pathways and whose role in breast cancer has not been previously described. PMID:22438871

  13. Loss of primary cilia occurs early in breast cancer development

    PubMed Central

    2014-01-01

    Background Primary cilia are microtubule-based organelles that protrude from the cell surface. Primary cilia play a critical role in development and disease through regulation of signaling pathways including the Hedgehog pathway. Recent mouse models have also linked ciliary dysfunction to cancer. However, little is known about the role of primary cilia in breast cancer development. Primary cilia expression was characterized in cancer cells as well as their surrounding stromal cells from 86 breast cancer patients by counting cilia and measuring cilia length. In addition, we examined cilia expression in normal epithelial and stromal cells from reduction mammoplasties as well as histologically normal adjacent tissue for comparison. Results We observed a statistically significant decrease in the percentage of ciliated cells on both premalignant lesions as well as in invasive cancers. This loss of cilia does not correlate with increased proliferative index (Ki67-positive cells). However, we did detect rare ciliated cancer cells present in patients with invasive breast cancer and found that these express a marker of basaloid cancers that is associated with poor prognosis (Cytokeratin 5). Interestingly, the percentage of ciliated stromal cells associated with both premalignant and invasive cancers decreased when compared to stromal cells associated with normal tissue. To understand how cilia may be lost during cancer development we analyzed the expression of genes required for ciliogenesis and/or ciliary function and compared their expression in normal versus breast cancer samples. We found that expression of ciliary genes were frequently downregulated in human breast cancers. Conclusions These data suggest that primary cilia are lost early in breast cancer development on both the cancer cells and their surrounding stromal cells. PMID:24987519

  14. Breast Cancer

    MedlinePlus

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

  15. [DNA aptamers selection for breast cancer].

    PubMed

    Zamay, G S; Belayanina, I V; Zamay, A S; Komarova, M A; Krat, A V; Eremina, E N; Zukov, R A; Sokolov, A E; Zamay, T N

    2016-05-01

    A method of selection of DNA aptamers to breast tumor tissue based on the use of postoperative material has been developed. Breast cancer tissues were used as the positive target; the negative targets included benign tumor tissue, adjacent healthy tissues, breast tissues from mastopathy patients, and also tissues of other types of malignant tumors. During selection a pool of DNA aptamers demonstrating selective binding to breast cancer cells and tissues and insignificant binding to breast benign tissues has been obtained. These DNA aptamers can be used for identification of protein markers, breast cancer diagnostics, and targeted delivery of anticancer drugs.

  16. Activation status of Wnt/ß-catenin signaling in normal and neoplastic breast tissues: relationship to HER2/neu expression in human and mouse.

    PubMed

    Khalil, Sara; Tan, Grace A; Giri, Dilip D; Zhou, Xi Kathy; Howe, Louise R

    2012-01-01

    Wnt/ß-catenin signaling is strongly implicated in neoplasia, but the role of this pathway in human breast cancer has been controversial. Here, we examined Wnt/ß-catenin pathway activation as a function of breast cancer progression, and tested for a relationship with HER2/neu expression, using a human tissue microarray comprising benign breast tissues, ductal carcinoma in situ (DCIS), and invasive carcinomas. Cores were scored for membranous ß-catenin, a key functional component of adherens junctions, and for nucleocytoplasmic ß-catenin, a hallmark of Wnt/ß-catenin pathway activation. Only 82% of benign samples exhibited membrane-associated ß-catenin, indicating a finite frequency of false-negative staining. The frequency of membrane positivity was similar in DCIS samples, but was significantly reduced in carcinomas (45%, P<0.001), consistent with loss of adherens junctions during acquisition of invasiveness. Negative membrane status in cancers correlated with higher grade (P = 0.04) and estrogen receptor-negative status (P = 0.03), both indices of poor prognosis. Unexpectedly, a substantial frequency of nucleocytoplasmic ß-catenin was observed in benign breast tissues (36%), similar to that in carcinomas (35%). Positive-staining basal nuclei observed in benign breast may identify putative stem cells. An increased frequency of nucleocytoplasmic ß-catenin was observed in DCIS tumors (56%), suggesting that pathway activation may be an early event in human breast neoplasia. A correlation was observed between HER2/neu expression and nucleocytoplasmic ß-catenin in node-positive carcinomas (P = 0.02). Furthermore, cytoplasmic ß-catenin was detected in HER2/neu-induced mouse mammary tumors. The Axin2(NLSlacZ) mouse strain, a previously validated reporter of mammary Wnt/ß-catenin signaling, was utilized to define in vivo transcriptional consequences of HER2/neu-induced ß-catenin accumulation. Discrete hyperplastic foci observed in mammary glands from

  17. Induction of apoptotic cell death by phytoestrogens by up-regulating the levels of phospho-p53 and p21 in normal and malignant estrogen receptor α-negative breast cells.

    PubMed

    Seo, Hye-Sook; Ju, Ji-Hyun; Jang, Kibeom; Shin, Incheol

    2011-02-01

    In this study, we investigated the underlying mechanism by which phytoestrogens suppress the growth of normal (MCF-10A) and malignant (MDA-MB-231) estrogen receptor α (ERα)-negative breast cells. We hypothesized that phytoestrogen inhibits the proliferation of ERα-negative breast cancer cells. We found that all tested phytoestrogens (genistein, apigenin, and quercetin) suppressed the growth of both MCF-10A and MDA-MB-231 cells, as revealed by proliferation assays. These results were accompanied by an increase in the sub-G0/G1 apoptotic fractions as well as an increase in the cell population in the G2/M phase in both cell types, as revealed by cell cycle analysis. When we assessed the effect of phytoestrogens on the level of intracellular signaling molecules by Western blot analysis, we found that phytoestrogens increased the level of active p53 (phospho-p53) without changing the p53 level in both MCF-10A and MDA-MB-231 cells. Phytoestrogens also induced an increase in p21, a p53 target gene, and a decrease in either Bcl-xL or cyclin B1 in both cell types. In contrast, the protein levels of phosphatase and tensin homolog, cyclin D1, cell division control protein 2 homolog, phospho-cell division control protein 2 homolog, and p27 were not changed after phytoestrogen treatment. Our data indicate that phytoestrogens induce apoptotic cell death of ERα-negative breast cancer cells via p53-dependent pathway and suggest that phytoestrogens may be promising agents in the treatment and prevention of ERα-negative breast cancer.

  18. Overexpression of histone demethylase JMJD5 promotes metastasis and indicates a poor prognosis in breast cancer.

    PubMed

    Zhao, Zhihua; Sun, Chuntao; Li, Fengqi; Han, Jiankui; Li, Xanjun; Song, Zhenguo

    2015-01-01

    In this study, we showed the expression of JMJD5 was increased in breast cancer tissues and breast adenocarcinoma cell lines MCF-7 as well as triple negative breast cancer cell lines MDA-MB-231 compared with paired adjacent normal mammary tissues and normal mammary epithelial cell lines MCF-10A. The higher expression of JMJD5 was significantly corresponded with clinical stage, histological grade and lymph node metastasis. Overexpression of JMJD5 promoted cell invasion and induce EMT, while JMJD5 siRNA inhibits MDA-MB-231 cells invasion in vitro. Moreover, qChIP analysis revealed the Snail family proteins Snai1 was the direct target of JMJD5 in breast cancer cells. Luciferase reporter assays suggested that the overexpression of JMJD5 resulted in the activation of Snail1 promoter-driven luciferase reporter. The changes in the level of RNA and protein implied that the activation of Snail was the important mechanisms by which JMJD5 triggers metastasis. We also detected the higher expression of JMJD5 protein was an independent unfavorable biomarker for worse overall survival in breast cancer patients. Therefore, our results identified an important role for JMJD5 in breast cancer through the regulation of snail1.

  19. Detection of Superior Markers for Polymerase Chain Reaction Diagnosis of Breast Cancer Micrometastasis in Sentinel Lymph Nodes.

    PubMed

    Alizadeh Shargh, Shohreh; Movafagh, Abolfazl; Zarghami, Nosratolah; Sayad, Arezou; Mansouri, Neda; Taheri, Mohammad; Heidary Pour, Atefeh; Iranpour, Mostafa; Ghaedi, Hamid; Montazeri, Vahid; Massoudi, Nilofar; Hashemi, Mehrdad; Mortazavi-Tabatabaei, S A

    2016-01-01

    Breast cancer is the most prevalent type of cancer among women around the world, and mortality is primarily caused by micro-metastatic disease. The complex mechanisms of breast cancer invasion and metastasis are intrinsically related to the malignant cell type so that early detection of micro-metastases can help prolongation of survival for patient. The aim of the present research work was evaluation of the expression status of mammoglobin protein as a candidate molecular marker in the negative sentinel lymph node (SLN). Fifty tumor specimens, and 50 normal adjacent breast tissue samples from the same patients were selected on the basis of having more than 10% tumor content for RNA extraction from SLNs. Tumor samples and normal adjacent breast tissue were archived in the form of frozen fresh tissue in liquid nitrogen. Real-time PCR was performed on a Bioner life express gradient thermal cycler system. Mammoglobin gene overexpression in breast cancer metastasis was investigated. Single marker results were mammaglobin 66.7% and CK19 50.0%, with 58.3% for the two in combination. Due to improved outcome with at least 3 genes (83.3%), it seems, triple marker evaluation will be most likely useful for detecting micro-metastases instead of studying separate genes. PMID:27165222

  20. Tight Junctions: A Barrier to the Initiation and Progression of Breast Cancer?

    PubMed Central

    Brennan, Kieran; Offiah, Gozie; McSherry, Elaine A.; Hopkins, Ann M.

    2010-01-01

    Breast cancer is a complex and heterogeneous disease that arises from epithelial cells lining the breast ducts and lobules. Correct adhesion between adjacent epithelial cells is important in determining the normal structure and function of epithelial tissues, and there is accumulating evidence that dysregulated cell-cell adhesion is associated with many cancers. This review will focus on one cell-cell adhesion complex, the tight junction (TJ), and summarize recent evidence that TJs may participate in breast cancer development or progression. We will first outline the protein composition of TJs and discuss the functions of the TJ complex. Secondly we will examine how alterations in these functions might facilitate breast cancer initiation or progression; by focussing on the regulatory influence of TJs on cell polarity, cell fate and cell migration. Finally we will outline how pharmacological targeting of TJ proteins may be useful in limiting breast cancer progression. Overall we hope to illustrate that the relationship between TJ alterations and breast cancer is a complex one; but that this area offers promise in uncovering fundamental mechanisms linked to breast cancer progression. PMID:19920867

  1. Field cancerization in mammary carcinogenesis - Implications for prevention and treatment of breast cancer.

    PubMed

    Rivenbark, Ashley G; Coleman, William B

    2012-12-01

    The natural history of breast cancer unfolds with the development of ductal carcinoma in situ (DCIS) in normal breast tissue, and evolution of this pre-invasive neoplasm into invasive cancer. The mechanisms that drive these processes are poorly understood, but evidence from the literature suggests that mammary carcinogenesis may occur through the process of field cancerization. Clinical observations are consistent with the idea that (i) DCIS may arise in a field of altered breast epithelium, (ii) narrow surgical margins do not remove the entire altered field (contributing to recurrence and/or disease progression), and (iii) whole-breast radiation therapy is effective in elimination of the residual field of altered cells adjacent to the resected DCIS. Molecular studies suggest that the field of altered breast epithelial cells may carry cancer-promoting genetic mutations (or other molecular alterations) or cancer promoting epimutations (oncogenic alterations in the epigenome). In fact, most breast cancers develop through a succession of molecular events involving both genetic mutations and epimutations. Hence, in hereditary forms of breast cancer, the altered field reflects the entire breast tissue which is composed of cells with a predisposing molecular lesion (such as a BRCA1 mutation). In the example of a BRCA1-mutant patient, it is evident that local resection of a DCIS lesion or localized but invasive cancer will not result in elimination of the altered field. In sporadic breast cancer patients, the mechanistic basis for the altered field may not be so easily recognized. Nonetheless, identification of the nature of field cancerization in a given patient may guide clinical intervention. Thus, patients with DCIS that develops in response to an epigenetic lesion (such as a hypermethylation defect affecting the expression of tumor suppressor genes) might be treated with epigenetic therapy to normalize the altered field and reduce the risk of secondary occurrence of

  2. Reactivity of a monoclonal antibody with tissues and tumors from the human breast. Immunohistochemical localization of a new antigen and clinicopathologic correlations.

    PubMed

    Mariani-Costantini, R; Barbanti, P; Colnaghi, M I; Ménard, S; Clemente, C; Rilke, F

    1984-04-01

    The reactions of a monoclonal antibody to the MCF7 breast cancer cell line were immunohistochemically studied on a variety of breast tumors, primary and metastatic, on mammary epithelium and on nonneoplastic breast lesions. A high proportion of positive reactions was observed in ductal, lobular, and tubular carcinomas as well as in mammary Paget's disease. Mucinous, medullary, and papillary carcinomas showed a low incidence of reactivity. Carcinomas with metaplasia, carcinoids, and nonepithelial breast tumors were unreactive with the antibody. Positive immunostaining was documented also in nodal and extranodal metastatic lesions. The staining of nodal metastases was correlated with the positive reaction of the primary tumor. Reactivity was widely distributed in normal breast epithelial cells and in benign breast lesions. Staining of nonneoplastic mammary epithelial was associated with reactivity of adjacent neoplastic tissues. Staining differences between nonneoplastic and neoplastic mammary tissues were related to the intensity and cytologic distribution of the labeling. Heterogeneous reactivity of morphologically similar cells was documented in nonneoplastic and neoplastic breast epithelial cells as well as in nodal and extranodal breast carcinoma metastases. Immunohistologically detectable antigen was not correlated with prognostic factors such as histologic grade or nodal status. A retrospective study of T1NO cases failed to substantiate any prognostic value for the reactivity of primary breast tumors with this monoclonal antibody.

  3. Discordant assessment of tumor biomarkers by histopathological and molecular assays in the EORTC randomized controlled 10041/BIG 03-04 MINDACT trial breast cancer : Intratumoral heterogeneity and DCIS or normal tissue components are unlikely to be the cause of discordance.

    PubMed

    Viale, Giuseppe; Slaets, Leen; de Snoo, Femke A; Bogaerts, Jan; Russo, Leila; van't Veer, Laura; Rutgers, Emiel J T; Piccart-Gebhart, Martine J; Stork-Sloots, Lisette; Dell'Orto, Patrizia; Glas, Annuska M; Cardoso, Fatima

    2016-02-01

    Accurate identification of breast cancer patients most likely to benefit from adjuvant systemic therapies is crucial. Better understanding of differences between methods can lead to an improved ER, PgR, and HER-2 assessment. The purpose of this preplanned translational research is to investigate the correlation of central IHC/FISH assessments with microarray mRNA readouts of ER, PgR, and HER-2 status in the MINDACT trial and to determine if any discordance could be attributed to intratumoral heterogeneity or the DCIS and normal tissue components in the specimens. MINDACT is an international, prospective, randomized, phase III trial investigating the clinical utility of MammaPrint in selecting patients with early breast cancer for adjuvant chemotherapy (n = 6694 patients). Gene-expression data were obtained by TargetPrint; IHC and/or FISH were assessed centrally (n = 5788; 86 %). Macroscopic and microscopic evaluation of centrally submitted FFPE blocks identified 1427 cases for which the very same sample was submitted for gene-expression analysis. TargetPrint ER had a positive agreement of 98 %, and a negative agreement of 95 % with central pathology. Corresponding figures for PgR were 85 and 94 % and for HER-2 72 and 99 %. Agreement of mRNA versus central protein was not different when the same or a different portion of the tumor tissue was analyzed or when DCIS and/or normal tissue was included in the sample subjected to mRNA assays. This is the first large analysis to assess the discordance rate between protein and mRNA analysis of breast cancer markers, and to look into intratumoral heterogeneity, DCIS, or normal tissue components as a potential cause of discordance. The observed difference between mRNA and protein assessment for PgR and HER-2 needs further research; the present analysis does not support intratumoral heterogeneity or the DCIS and normal tissue components being likely causes of the discordance.

  4. Ultrasound - Breast

    MedlinePlus

    ... discharge) and to characterize potential abnormalities seen on mammography or breast magnetic resonance imaging (MRI). Ultrasound imaging ... supply in breast lesions . Supplemental Breast Cancer Screening Mammography is the only screening tool for breast cancer ...

  5. Breast pain

    MedlinePlus

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

  6. The role of non-coding RNAs in the regulation of stem cells and progenitors in the normal mammary gland and in breast tumors

    PubMed Central

    Tordonato, Chiara; Di Fiore, Pier Paolo; Nicassio, Francesco

    2015-01-01

    The outlook on stem cell (SC) biology is shifting from a rigid hierarchical to a more flexible model in which the identity and the behavior of adult SCs, far from being fixed, are determined by the dynamic integration of cell autonomous and non-autonomous mechanisms. Within this framework, the recent discovery of thousands of non-coding RNAs (ncRNAs) with regulatory function is redefining the landscape of transcriptome regulation, highlighting the interplay of epigenetic, transcriptional, and post-transcriptional mechanisms in the specification of cell fate and in the regulation of developmental processes. Furthermore, the expression of ncRNAs is often tissue- or even cell type-specific, emphasizing their involvement in defining space, time and developmental stages in gene regulation. Such a role of ncRNAs has been investigated in embryonic and induced pluripotent SCs, and in numerous types of adult SCs and progenitors, including those of the breast, which will be the topic of this review. We will focus on ncRNAs with an important role in breast cancer, in particular in mammary cancer SCs and progenitors, and highlight the ncRNA-based circuitries whose subversion alters a number of the epigenetic, transcriptional, and post-transcriptional events that control “stemness” in the physiological setting. PMID:25774169

  7. Multifunctional T Lymphocytes Generated After Therapy With an Antitumor Gallotanin-Rich Normalized Fraction Are Related to Primary Tumor Size Reduction in a Breast Cancer Model.

    PubMed

    Urueña, Claudia; Gomez, Alejandra; Sandoval, Tito; Hernandez, John; Li, Shaoping; Barreto, Alfonso; Fiorentino, Susana

    2015-09-01

    Natural compounds are promising sources for anticancer therapies because of their multifunctional activity and low toxicity. Although the host immune response (IR) is clearly implicated in tumor control, the relationship between natural therapies and IR has not yet been elucidated. The present work evaluates IR induction after treatment with a gallotannin-rich fraction from Caesalpinia spinosa (P2Et). Breast tumor 4T1 cells were used to evaluate antitumor properties and IR activation. Apoptosis and expression of immunogenic cell death (ICD) markers were assessed in vitro, whereas IR and postvaccination tumor evolution were assessed in vivo. P2Et fraction induced apoptotic cell death, displaying phosphatidylserine externalization and DNA fragmentation. ICD markers such as calreticulin, high-mobility group box 1 translocation from nuclei to cytoplasm, and ATP secretion were observed. Primary tumor control was improved by vaccination with P2Et-pretreated 4T1 cells (t-P2Et), yielding long-lasting ex vivo multifunctional CD4(+) and CD8(+) T lymphocytes (interleukin [IL]-2(+), tumor necrosis factor [TNF]-α(+), interferon [IFN]-γ(+)) that secrete IL-2, TNF-α, IL-4, IL-5, and IFN-γ after specific 4T1 cell stimulation. The present study constitutes the first demonstration of a long-lasting antitumor IR induction and primary tumor reduction induced by a complex natural fraction. These data reveal the potential use of this fraction as an adjuvant in breast cancer treatment.

  8. Why Are My Breasts Different Sizes?

    MedlinePlus

    ... breasts is perfectly normal. It's quite common for girls to have different-sized breasts or nipples, especially ... its partner — is quite common in humans. When girls begin puberty, usually between the ages of 8 ...

  9. ID4 controls luminal lineage commitment in normal mammary epithelium and inhibits BRCA1 function in basal-like breast cancer.

    PubMed

    Baker, Laura A; Holliday, Holly; Swarbrick, Alexander

    2016-09-01

    Inhibitor of differentiation (ID) proteins are key regulators of development and tumorigenesis. One member of this family, ID4, controls lineage commitment during mammary gland development by acting upstream of key developmental pathways. Recent evidence suggests an emerging role for ID4 as a lineage-dependent proto-oncogene that is overexpressed and amplified in a subset of basal-like breast cancers (BLBCs), conferring poor prognosis. Several lines of evidence suggest ID4 may suppress BRCA1 function in BLBC and in doing so, define a subset of BLBC patients who may respond to therapies traditionally used in BRCA1-mutant cancers. This review highlights recent advances in our understanding of the requirement for ID4 in mammary lineage commitment and the role for ID4 in BLBC. We address current shortfalls in this field and identify important areas of future research. PMID:27412917

  10. What Is Breast Cancer?

    MedlinePlus

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

  11. Optimal reference genes for normalization of qRT-PCR data from archival formalin-fixed, paraffin-embedded breast tumors controlling for tumor cell content and decay of mRNA.

    PubMed

    Tramm, Trine; Sørensen, Brita S; Overgaard, Jens; Alsner, Jan

    2013-09-01

    Reliable determination of gene-expression levels from qRT-PCR requires accurate normalization of target genes to reference genes in order to remove nonbiological variation. Reference genes are ideally constitutively expressed in every cell, but many genes used for normalization has been shown to vary with tissue type, cellular proliferation, cancer progression, and degradation of nucleic acids. Gene-expression analysis is increasingly performed on degraded mRNA from formalin-fixed, paraffin-embedded tissue (FFPE), giving the option of examining retrospective cohorts. The aim of this study was to select robust reference genes showing stable expression over time in FFPE, controlling for various content of tumor tissue and decay of mRNA because of variable length of storage of the tissue. Sixteen reference genes were quantified by qRT-PCR in 40 FFPE breast tumor samples, stored for 1 to 29 years. Samples included 2 benign lesions and 38 carcinomas with varying tumor content. Stability of the reference genes were determined by the geNorm algorithm. mRNA was successfully extracted from all samples, and the 16 genes quantified in the majority of samples. Results showed 14% loss of amplifiable mRNA per year, corresponding to a half-life of 4.6 years. The 4 most stable expressed genes were CALM2, RPL37A, ACTB, and RPLP0. Several of the other examined genes showed considerably instability over time (GAPDH, PSMC4, OAZ1, IPO8). In conclusion, we identified 4 genes robustly expressed over time and independent of neoplastic tissue content in the FFPE block. Other widely used reference genes were concluded to be less suited for retrospective analysis of FFPE breast samples.

  12. A functional single nucleotide polymorphism of SET8 is prognostic for breast cancer

    PubMed Central

    Song, Fengju; Liu, Qun; Dai, Hongji; Zheng, Hong; Cui, Ping; Zhang, Lina; Zhang, Wei; Chen, Kexin

    2016-01-01

    A single-nucleotide polymorphism (SNP) locus rs16917496 (T > C) within the 3′-untranslated region (3′-UTR) of SET8 was associated with susceptibility in several malignancies including breast cancer. To further elucidate the prognostic relevance of this SNP in breast cancer, we conducted a clinical study as well as SET8 expression analysis in a cohort of 1,190 breast cancer patients. We demonstrated the expression levels of SET8 in TT genotype were higher than in CC genotypes, and high levels of SET8 were associated with poor survival. SET8 expression was significantly higher in breast tumor tissue than in paired adjacent normal tissue. In addition, survival analysis in 315 patients showed SNP rs16917496 was an independent prognostic factor of breast cancer outcome with TT genotype associated with poor survival compared with CC/CT genotypes. Thus, this SNP may serve as a genetic prognostic factor and a treatment target for breast cancer. Future studies are warranted. PMID:27144429

  13. Molecular disorganization of axons adjacent to human lacunar infarcts.

    PubMed

    Hinman, Jason D; Lee, Monica D; Tung, Spencer; Vinters, Harry V; Carmichael, S Thomas

    2015-03-01

    Cerebral microvascular disease predominantly affects brain white matter and deep grey matter, resulting in ischaemic damage that ranges from lacunar infarcts to white matter hyperintensities seen on magnetic resonance imaging. These lesions are common and result in both clinical stroke syndromes and accumulate over time, resulting in cognitive deficits and dementia. Magnetic resonance imaging studies suggest that these lesions progress over time, accumulate adjacent to prior lesions and have a penumbral region susceptible to further injury. The pathological correlates of this adjacent injury in surviving myelinated axons have not been previously defined. In this study, we sought to determine the molecular organization of axons in tissue adjacent to lacunar infarcts and in the regions surrounding microinfarcts, by determining critical elements in axonal function: the morphology and length of node of Ranvier segments and adjacent paranodal segments. We examined post-mortem brain tissue from six patients with lacunar infarcts and tissue from two patients with autosomal dominant retinal vasculopathy and cerebral leukoencephalopathy (previously known as hereditary endotheliopathy with retinopathy, nephropathy and stroke) who accumulate progressive white matter ischaemic lesions in the form of lacunar and microinfarcts. In axons adjacent to lacunar infarcts yet extending up to 150% of the infarct diameter away, both nodal and paranodal length increase by ∼20% and 80%, respectively, reflecting a loss of normal cell-cell adhesion and signalling between axons and oligodendrocytes. Using premorbid magnetic resonance images, brain regions from patients with retinal vasculopathy and cerebral leukoencephalopathy that harboured periventricular white matter hyperintensities were selected and the molecular organization of axons was determined within these regions. As in regions adjacent to lacunar infarcts, nodal and paranodal length in white matter of these patients is

  14. Molecular disorganization of axons adjacent to human lacunar infarcts

    PubMed Central

    Lee, Monica D.; Tung, Spencer; Vinters, Harry V.; Carmichael, S. Thomas

    2015-01-01

    Cerebral microvascular disease predominantly affects brain white matter and deep grey matter, resulting in ischaemic damage that ranges from lacunar infarcts to white matter hyperintensities seen on magnetic resonance imaging. These lesions are common and result in both clinical stroke syndromes and accumulate over time, resulting in cognitive deficits and dementia. Magnetic resonance imaging studies suggest that these lesions progress over time, accumulate adjacent to prior lesions and have a penumbral region susceptible to further injury. The pathological correlates of this adjacent injury in surviving myelinated axons have not been previously defined. In this study, we sought to determine the molecular organization of axons in tissue adjacent to lacunar infarcts and in the regions surrounding microinfarcts, by determining critical elements in axonal function: the morphology and length of node of Ranvier segments and adjacent paranodal segments. We examined post-mortem brain tissue from six patients with lacunar infarcts and tissue from two patients with autosomal dominant retinal vasculopathy and cerebral leukoencephalopathy (previously known as hereditary endotheliopathy with retinopathy, nephropathy and stroke) who accumulate progressive white matter ischaemic lesions in the form of lacunar and microinfarcts. In axons adjacent to lacunar infarcts yet extending up to 150% of the infarct diameter away, both nodal and paranodal length increase by ∼20% and 80%, respectively, reflecting a loss of normal cell-cell adhesion and signalling between axons and oligodendrocytes. Using premorbid magnetic resonance images, brain regions from patients with retinal vasculopathy and cerebral leukoencephalopathy that harboured periventricular white matter hyperintensities were selected and the molecular organization of axons was determined within these regions. As in regions adjacent to lacunar infarcts, nodal and paranodal length in white matter of these patients is

  15. Analysis of adjacent segment reoperation after lumbar total disc replacement

    PubMed Central

    Rainey, Scott; Blumenthal, Scott L.; Zigler, Jack E.; Guyer, Richard D.; Ohnmeiss, Donna D.

    2012-01-01

    Background Fusion has long been used for treating chronic back pain unresponsive to nonoperative care. However, potential development of adjacent segment degeneration resulting in reoperation is a concern. Total disc replacement (TDR) has been proposed as a method for addressing back pain and preventing or reducing adjacent segment degeneration. The purpose of the study was to determine the reoperation rate at the segment adjacent to a level implanted with a lumbar TDR and to analyze the pre-TDR condition of the adjacent segment. Methods This study was based on a retrospective review of charts and radiographs from a consecutive series of 1000 TDR patients to identify those who underwent reoperation because of adjacent segment degeneration. Some of the patients were part of randomized studies comparing TDR with fusion. Adjacent segment reoperation data were also collected from 67 patients who were randomized to fusion in those studies. The condition of the adjacent segment before the index surgery was compared with its condition before reoperation based on radiographs, magnetic resonance imaging (MRI), and computed tomography. Results Of the 1000 TDR patients, 20 (2.0%) underwent reoperation. The mean length of time from arthroplasty to reoperation was 28.3 months (range, 0.5–85 months). Of the adjacent segments evaluated on preoperative MRI, 38.8% were normal, 38.8% were moderately diseased, and 22.2% were classified as having severe degeneration. None of these levels had a different grading at the time of reoperation compared with the pre-TDR MRI study. Reoperation for adjacent segment degeneration was performed in 4.5% of the fusion patients. Conclusions The 2.0% rate of adjacent segment degeneration resulting in reoperation in this study is similar to the 2.0% to 2.8% range in other studies and lower than the published rates of 7% to 18% after lumbar fusion. By carefully assessing the presence of pre-existing degenerative changes before performing arthroplasty

  16. Expression of activator protein-1 (AP-1) family members in breast cancer

    PubMed Central

    2013-01-01

    Background The activator protein-1 (AP-1) transcription factor is believed to be important in tumorigenesis and altered AP-1 activity was associated with cell transformation. We aimed to assess the potential role of AP-1 family members as novel biomarkers in breast cancer. Methods We studied the expression of AP-1 members at the mRNA level in 72 primary breast tumors and 37 adjacent non-tumor tissues and evaluated its correlation with clinicopathological parameters including estrogen receptor (ER), progesterone receptor (PR) and HER2/neu status. Expression levels of Ubiquitin C (UBC) were used for normalization. Protein expression of AP-1 members was assessed using Western blot analysis in a subset of tumors. We used student’s t-test, one-way ANOVA, logistic regression and Pearson’s correlation coefficient for statistical analyses. Results We found significant differences in the expression of AP-1 family members between tumor and adjacent non-tumor tissues for all AP-1 family members except Fos B. Fra-1, Fra-2, Jun-B and Jun-D mRNA levels were significantly higher in tumors compared to adjacent non-tumor tissues (p < 0.001), whilst c-Fos and c-Jun mRNA levels were significantly lower in tumors compared with adjacent non-tumor tissues (p < 0.001). In addition, Jun-B overexpression had outstanding discrimination ability to differentiate tumor tissues from adjacent non-tumor tissues as determined by ROC curve analysis. Moreover, Fra-1 was significantly overexpressed in the tumors biochemically classified as ERα negative (p = 0.012) and PR negative (p = 0.037). Interestingly, Fra-1 expression was significantly higher in triple-negative tumors compared with luminal carcinomas (p = 0.01). Conclusions Expression levels of Fra-1 and Jun-B might be possible biomarkers for prognosis of breast cancer. PMID:24073962

  17. Detection and Analysis of Human Papillomavirus (HPV) DNA in Breast Cancer Patients by an Effective Method of HPV Capture

    PubMed Central

    Liu, Xiao; Lv, Yonggang; Wu, Jinghua; Zhuang, Xuehan; Zhang, Juliang; Zhao, Yi; Huang, Haodong; Fan, Jing; Yao, Qing; He, Chenyang; Zhang, Xiuqing; Huang, Chen; Chen, Jianghao; Wang, Ling

    2014-01-01

    Despite an increase in the number of molecular epidemiological studies conducted in recent years to evaluate the association between human papillomavirus (HPV) and the risk of breast carcinoma, these studies remain inconclusive. Here we aim to detect HPV DNA in various tissues from patients with breast carcinoma using the method of HPV capture combined with massive paralleled sequencing (MPS). To validate the confidence of our methods, 15 cervical cancer samples were tested by PCR and the new method. Results showed that there was 100% consistence between the two methods.DNA from peripheral blood, tumor tissue, adjacent lymph nodes and adjacent normal tissue were collected from seven malignant breast cancer patients, and HPV type 16(HPV16) was detected in 1/7, 1/7, 1/7and 1/7 of patients respectively. Peripheral blood, tumor tissue and adjacent normal tissue were also collected from two patients with benign breast tumor, and 1/2, 2/2 and 2/2 was detected to have HPV16 DNA respectively. MPS metrics including mapping ratio, coverage, depth and SNVs were provided to characterize HPV in samples. The average coverage was 69% and 61.2% for malignant and benign samples respectively. 126 SNVs were identified in all 9 samples. The maximum number of SNVs was located in the gene of E2 and E4 among all samples. Our study not only provided an efficient method to capture HPV DNA, but detected the SNVS, coverage, SNV type and depth. The finding has provided further clue of association between HPV16 and breast cancer. PMID:24614680

  18. Dense Breasts

    MedlinePlus

    ... woman’s breasts. It is most commonly determined using mammography, a diagnostic test that uses low dose x- ... woman’s breasts, which is most commonly determined through mammography. The breast is made up of glandular, connective, ...

  19. Breast Diseases

    MedlinePlus

    Most women experience breast changes at some time. Your age, hormone levels, and medicines you take may cause lumps, bumps, and discharges (fluids that are not breast milk). If you have a breast lump, pain, ...

  20. EPHA7 and EPHA10 Physically Interact and Differentially Co-localize in Normal Breast and Breast Carcinoma Cell Lines, and the Co-localization Pattern Is Altered in EPHB6-expressing MDA-MB-231 Cells.

    PubMed

    Johnson, Candace; Segovia, Briana; Kandpal, Raj P

    Erythropoietin-producing hepatocellular carcinoma cell (EPH) receptors comprise the most abundant receptor tyrosine kinase family characterized to date in mammals including humans. These proteins are involved in axon guidance, tissue organization, vascular development and the intricate process of various diseases including cancer. These diverse functions of EPH receptors are attributed, in part, to their abilities for heterodimerization. While the interacting partners of kinase-deficient EPHB6 receptor have been characterized, the interaction of the kinase-dead EPHA10 with any other receptor has not been identified. By using co-immunoprecipitation, we demonstrated physical interaction between kinase-deficient EPHA10 with kinase-sufficient EPHA7 receptor. Immunocytochemical analyses have revealed that these two receptors co-localize on the cell surface, and soluble portions of the receptors exist as a complex in the cytoplasm as well as the nuclei. While EPHA7 and EPHA10 co-localize similarly on the membrane in MCF10A and MCF7 cells, they were differentially co-localized in MDA-MB-231 cells stably transfected with empty pcDNA vector (MDA-MB-231-PC) or an expression construct of EPHB6 (MDA-MB-231-B6). The full-length isoforms of these receptors were co-localized on the cell surface, and the soluble forms were present as a complex in the cytoplasm as well as the nucleus in MDA-MB-231-PC cells. MDA-MB-231-B6 cells, on the other hand, were distinguished by the absence of any signal in the nuclei. Our results represent the first demonstration of physical interaction between EPHA10 and EPHA7 and their cellular co-localization. Furthermore, these observations also suggest gene-regulatory functions of the complex of the soluble forms of these receptors in breast carcinoma cells of differential invasiveness. PMID:27566654

  1. Androgens and the breast.

    PubMed

    Dimitrakakis, Constantine; Bondy, Carolyn

    2009-01-01

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

  2. Androgens and the breast

    PubMed Central

    2009-01-01

    Androgens have important physiological effects in women while at the same time they may be implicated in breast cancer pathologies. However, data on the effects of androgens on mammary epithelial proliferation and/or breast cancer incidence are not in full agreement. We performed a literature review evaluating current clinical, genetic and epidemiological data regarding the role of androgens in mammary growth and neoplasia. Epidemiological studies appear to have significant methodological limitations and thus provide inconclusive results. The study of molecular defects involving androgenic pathways in breast cancer is still in its infancy. Clinical and nonhuman primate studies suggest that androgens inhibit mammary epithelial proliferation and breast growth while conventional estrogen treatment suppresses endogenous androgens. Abundant clinical evidence suggests that androgens normally inhibit mammary epithelial proliferation and breast growth. Suppression of androgens using conventional estrogen treatment may thus enhance estrogenic breast stimulation and possibly breast cancer risk. Addition of testosterone to the usual hormone therapy regimen may diminish the estrogen/progestin increase in breast cancer risk but the impact of this combined use on mammary gland homeostasis still needs evaluation. PMID:19889198

  3. Tumor suppressive function of mir-205 in breast cancer is linked to HMGB3 regulation.

    PubMed

    Elgamal, Ola A; Park, Jong-Kook; Gusev, Yuriy; Azevedo-Pouly, Ana Clara P; Jiang, Jinmai; Roopra, Avtar; Schmittgen, Thomas D

    2013-01-01

    Identifying targets of dysregulated microRNAs (miRNAs) will enhance our understanding of how altered miRNA expression contributes to the malignant phenotype of breast cancer. The expression of miR-205 was reduced in four breast cancer cell lines compared to the normal-like epithelial cell line MCF10A and in tumor and metastatic tissues compared to adjacent benign breast tissue. Two predicted binding sites for miR-205 were identified in the 3' untranslated region of the high mobility group box 3 gene, HMGB3. Both dual-luciferase reporter assay and Western blotting confirmed that miR-205 binds to and regulates HMGB3. To further explore miR-205 targeting of HMGB3, WST-1 proliferation and in vitro invasion assays were performed in MDA-MB-231 and BT549 cells transiently transfected with precursor miR-205 oligonucleotide or HMGB3 small interfering RNA (siRNA). Both treatments reduced the proliferation and invasion of the cancer cells. The mRNA and protein levels of HMGB3 were higher in the tumor compared to adjacent benign specimens and there was an indirect correlation between the expression of HMGB3 mRNA and patient survival. Treatment of breast cancer cells with 5-Aza/TSA derepressed miR-205 and reduced HMGB3 mRNA while knockdown of the transcriptional repressor NRSF/REST, reduced miR-205 and increased HMGB3. In conclusion, regulation of HMGB3 by miR-205 reduced both proliferation and invasion of breast cancer cells. Our findings suggest that modulating miR-205 and/or targeting HMGB3 are potential therapies for advanced breast cancer. PMID:24098490

  4. Circulating Proteolytic Products of Carboxypeptidase N for Early Detection of Breast Cancer

    PubMed Central

    Li, Yaojun; Li, Yueguo; Chen, Tao; Kuklina, Anna; Bernard, Paul; Esteva, Francisco J.; Shen, Haifa; Ferrari, Mauro; Hu, Ye

    2014-01-01

    Background Carboxypeptidase N (CPN) plays an important role in regulating vasoactive peptide hormones, growth factors, and cytokines by specifically cleaving their C-terminal basic residues. Herein we demonstrated that the circulating peptides specifically cleaved by CPN in the tumor microenvironment can indeed be stage-specific indicators of breast cancer. Methods The activity of CPN was evaluated using an ex-vivo peptide cleavage assay, in which synthesized C3f peptide (His6-C3f_S1304-R1320-His6) is incubated in interstitial fluids of breast tumor and adjacent normal breast tissues in mice with orthotopic implantation of the human cell line MDA-MB-231. Fragment profiling, by an approach combining nanopore fractionation and mass spectrometry, revealed the nature and extent of cleavage by CPN. These results correlated with the level of CPN-catalyzed peptides in blood specimens taken from the tumor-bearing mice, healthy women and breast cancer patients. CPN expression in the same set of samples was further examined by immunohistochemistry and immunoblotting. Results We showed that generation of C3f_R1310-L1319 specifically correlated with the CPN expression level. In both the mouse and clinical patient samples, the amount of CPN was clearly increased in tumor tissues compared to that seen in normal breast tissue, while its counterpart in blood remained constant. The amount of 6 CPN-catalyzed peptides predominantly increased in sera taken from the mice (n=8) at 2 weeks after orthotropic implantation. Six homologous peptides displayed the significantly higher expression in the patients’ plasma as early as the first pathologic stage of breast cancer. Conclusions The amount of circulating CPN-catalyzed peptides reported here reflects the extent of this enzyme’s activity in tumors, and our results clearly indicate their strong potential as biomarkers for non-invasive and early diagnosis of breast cancer. PMID:24146311

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

    PubMed

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

    2016-04-25

    The aim of this study was to evaluate the anticancer effect of atranorin (ATR) on murine 4T1 breast carcinoma cells and compare its sensitivity with normal mammary epithelial NMuMG cells in vitro. Anti-tumor and hepatoprotective activity of ATR-therapy was examined on mouse model of 4T1-induced cancer disease. ATR significantly reduced clonogenic ability of carcinoma 4T1 cells at the concentration of 75 μM, but clonogenicity of normal NMuMG cells was not affected by any of ATR concentrations tested. Moreover, flow cytometric and BrdU incorporation analysis did not confirm the inhibited entry into S-phase of the cell cyle after ATR incubation, and on the contrary, it induced apoptosis associated with the activation of caspase-3 and PARP cleavage in 4T1 cells. Although ATR did not cause any significant changes in Bcl-xL protein expression in NMuMG cells, an apparent depletion of Bcl-xL protein in 4T1 cells after 48 h ATR therapy was confirmed. Based on this result as well as the result of the total cell number decline, we can conclude that 4T1 cells are more sensitive to ATR therapy than NMuMG cells. ATR administration resulted in significantly longer survival time of BALB/c mice inoculated with 4T1 cells, what was associated with reduced tumor size and the higher numbers of apoptotic 4T1 cells. No differences were recorded in the number of BrdU-positive tumor cells between ATR-treated group and controls. Results indicate that ATR has rather proapoptotic than antiproliferative effect on 4T1 cells in vitro and in vivo and normal NMuMG cells are less sensitive to ATR. Furthermore, our studies revealed protective effect of ATR against oxidative stress in the livers of the tumor-bearing mice. PMID:26969521

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

    PubMed

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

    2016-04-25

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

  7. Breast MRI scan

    MedlinePlus

    MRI - breast; Magnetic resonance imaging - breast; Breast cancer - MRI; Breast cancer screening - MRI ... the same breast or the other breast after breast cancer has been diagnosed Distinguish between scar tissue and ...

  8. Signal transducer and activator of transcription 5 as a key signaling pathway in normal mammary gland developmental biology and breast cancer.

    PubMed

    Furth, Priscilla A; Nakles, Rebecca E; Millman, Sarah; Diaz-Cruz, Edgar S; Cabrera, M Carla

    2011-10-12

    STAT5 consists of two proteins, STAT5A/B, that impact mammary cell differentiation, proliferation, and survival. In normal development, STAT5 expression and activity are regulated by prolactin signaling with JAK2/ELF5, EGF signaling networks that include c-Src, and growth hormone, insulin growth factor, estrogen, and progesterone signaling pathways. In cancer, erythropoietin signaling can also regulate STAT5. Activation levels are influenced by AKT, caveolin, PIKE-A, Pak1, c-Myb, Brk, beta-integrin, dystroglycan, other STATs, and STAT pathway molecules JAK1, Shp2, and SOCS. TGF-β and PTPN9 can downregulate prolactin- and EGF-mediated STAT5 activation, respectively. IGF, AKT, RANKL, cyclin D1, BCL6, and HSP90A lie downstream of STAT5.

  9. Arm Selection Preference of MicroRNA-193a Varies in Breast Cancer

    PubMed Central

    Tsai, Kuo-Wang; Leung, Chung-Man; Lo, Yi-Hao; Chen, Ting-Wen; Chan, Wen-Ching; Yu, Shou-Yu; Tu, Ya-Ting; Lam, Hing-Chung; Li, Sung-Chou; Ger, Luo-Ping; Liu, Wen-Shan; Chang, Hong-Tai

    2016-01-01

    MicroRNAs (miRNAs) are short noncoding RNAs derived from the 3′ and 5′ ends of the same precursor. However, the biological function and mechanism of miRNA arm expression preference remain unclear in breast cancer. We found significant decreases in the expression levels of miR-193a-5p but no significant differences in those of miR-193a-3p in breast cancer. MiR-193a-3p suppressed breast cancer cell growth and migration and invasion abilities, whereas miR-193a-5p suppressed cell growth but did not influence cell motility. Furthermore, NLN and CCND1, PLAU, and SEPN1 were directly targeted by miR-193a-5p and miR-193a-3p, respectively, in breast cancer cells. The endogenous levels of miR-193a-5p and miR-193a-3p were significantly increased by transfecting breast cancer cells with the 3′UTR of their direct targets. Comprehensive analysis of The Cancer Genome Atlas database revealed significant differences in the arm expression preferences of several miRNAs between breast cancer and adjacent normal tissues. Our results collectively indicate that the arm expression preference phenomenon may be attributable to the target gene amount during breast cancer progression. The miRNA arm expression preference may be a means of modulating miRNA function, further complicating the mRNA regulatory network. Our findings provide a new insight into miRNA regulation and an application for breast cancer therapy. PMID:27307030

  10. Notch-1 promotes breast cancer cells proliferation by regulating LncRNA GAS5

    PubMed Central

    Pei, Jing; Wang, Benzhong

    2015-01-01

    Background: Notch signaling is indicated as novel therapeutic targets to prevent recurrence of breast cancer. LncRNAs were identified as downstream target of Notch pathway. However, the exact mechanisms involved in Notch signaling, lncRNAs and breast cancer remain to be explained. Objective: This original research aimed to determine the prognostic implications of Notch-1 for breast cancer, and explain mechanisms involved in regulation of lnRNA GAS5 by Notch-1, and identify the function of this mechanism on breast cancer. Method: Thirty breast cancer patients were included from The First Affiliated Hospital of Anhui Medical University (China) since January 2006 in this study. The mRNA level by RT-PCR and protein level of Notch-1 by western blot in tumor tissues and adjacent normal tissues were evaluated and 5-year survival analysis was applied to examine the significance of Notch-1. The levels of ten reported lncRNAs were determined by RT-PCR, and subsequently linear analysis was applied to analyze the relationship between these four unique lncRNAs and protein level of Notch-1, which identified the most relevant lncRNA GAS5 with Notch-1 in breast cancer. Subsequently, Notch1-siRNA was applied to influence the expression of Notch-1 in T47D, then the level of RSA5 was measured by RT-PCR, and CCK-8 assay was applied to measure the proliferation of T47D cells. Results: High level of Notch-1 provided a poor prognosis in breast cancer. Interference of Notch-1 significantly suppressed proliferation of T47D cell (P < 0.05), and significantly increased the level of GAS5. Conclusion: Notch-1 promotes breast cancer cells proliferation by regulating LncRNA GAS5. PMID:26550436

  11. Role of the Drug Transporter ABCC3 in Breast Cancer Chemoresistance

    PubMed Central

    Balaji, Sai A.; Udupa, Nayanabhirama; Chamallamudi, Mallikarjuna Rao; Gupta, Vaijayanti; Rangarajan, Annapoorni

    2016-01-01

    Increased expression of ABC-family of transporters is associated with chemotherapy failure. Although the drug transporters ABCG2, ABCB1 and ABCC1 have been majorly implicated in cancer drug resistance, recent studies have associated ABCC3 with multi drug resistance and poor clinical response. In this study, we have examined the expression of ABCC3 in breast cancers and studied its role in drug resistance and stemness of breast cancer cells in comparison with the more studied ABCC1. We observed that similar to ABCC1, the transcripts levels of ABCC3 was significantly high in breast cancers compared to adjacent normal tissue. Importantly, expression of both transporters was further increased in chemotherapy treated patient samples. Consistent with this, we observed that treatment of breast cancer cell lines with anti-cancer agents increased their mRNA levels of both ABCC1 and ABCC3. Further, similar to knockdown of ABCC1, knockdown of ABCC3 also significantly increased the retention of chemotherapeutic drugs in breast cancer cells and rendered them more chemo-sensitive. Interestingly, ABCC1 and ABCC3 knockdown cells also showed reduction in the expression of stemness genes, while ABCC3 knockdown additionally led to a reduction in the CD44high/CD24low breast cancer stem-like subpopulation. Consistent with this, their ability to form primary tumours was compromised. Importantly, down-modulation of ABCC3 rendered these cells increasingly susceptible to doxorubicin in xenograft mice models in vivo. Thus, our study highlights the importance of ABCC3 transporters in drug resistance to chemotherapy in the context of breast cancer. Further, these results suggest that combinatorial inhibition of these transporters together with standard chemotherapy can reduce therapy-induced resistance in breast cancer. PMID:27171227

  12. The Status of STAT3 and STAT5 in Human Breast Atypical Ductal Hyperplasia.

    PubMed

    Shi, Aiping; Dong, Jie; Hilsenbeck, Susan; Bi, Lirong; Zhang, Hong; Li, Yi

    2015-01-01

    Signal Transducer and Activation of Transcription factors (STAT3 and STAT5) play important roles in breast epithelial cell differentiation, proliferation, and apoptosis. They have been investigated extensively in established breast cancer, but their activation status in precancerous lesions has not been reported. Formalin-fixed, paraffin-embedded archival tissues from 59 cases of atypical ductal hyperplasia (ADH) and 31 cases of normal human breast tissue as well as 21 cases of usual ductal hyperplasias (UDH) were obtained from the First Hospital of Jilin University, China, and stained for pSTAT3 and pSTAT5 by immunohistochemistry. The median percentage of pSTAT5+ cells in ADH was 12%, not significantly deviant from that in normal breast. The median percentage of pSTAT3+ cells in ADH was 30%, significantly higher than that of normal breast. pSTAT3 and pSTAT5 were exclusive of each other--they were detected in different ADHs or in different cells within the same ADHs. In addition, both pSTAT3 and pSTAT5 were produced in similar percentages of cells in ADHs from cancer-free patients vs. ADHs that were adjacent to an invasive cancer. Our finding of a complementary expression pattern of pSTAT3 and pSTAT5 in ADH suggests that these two transcription factors may have feedback inhibitory effects on each other during early stages of breast cancer evolution, and that disruption of this inverse relationship may be important in the progression from early lesions to cancer, which exhibits positive association between pSTAT3 and pSTAT5. PMID:26146825

  13. The Status of STAT3 and STAT5 in Human Breast Atypical Ductal Hyperplasia

    PubMed Central

    Shi, Aiping; Dong, Jie; Hilsenbeck, Susan; Bi, Lirong; Zhang, Hong; Li, Yi

    2015-01-01

    Signal Transducer and Activation of Transcription factors (STAT3 and STAT5) play important roles in breast epithelial cell differentiation, proliferation, and apoptosis. They have been investigated extensively in established breast cancer, but their activation status in precancerous lesions has not been reported. Formalin-fixed, paraffin-embedded archival tissues from 59 cases of atypical ductal hyperplasia (ADH) and 31 cases of normal human breast tissue as well as 21 cases of usual ductal hyperplasias (UDH) were obtained from the First Hospital of Jilin University, China, and stained for pSTAT3 and pSTAT5 by immunohistochemistry. The median percentage of pSTAT5+ cells in ADH was 12%, not significantly deviant from that in normal breast. The median percentage of pSTAT3+ cells in ADH was 30%, significantly higher than that of normal breast. pSTAT3 and pSTAT5 were exclusive of each other—they were detected in different ADHs or in different cells within the same ADHs. In addition, both pSTAT3 and pSTAT5 were produced in similar percentages of cells in ADHs from cancer-free patients vs. ADHs that were adjacent to an invasive cancer. Our finding of a complementary expression pattern of pSTAT3 and pSTAT5 in ADH suggests that these two transcription factors may have feedback inhibitory effects on each other during early stages of breast cancer evolution, and that disruption of this inverse relationship may be important in the progression from early lesions to cancer, which exhibits positive association between pSTAT3 and pSTAT5. PMID:26146825

  14. Over-expression of genes and proteins of ubiquitin specific peptidases (USPs) and proteasome subunits (PSs) in breast cancer tissue observed by the methods of RFDD-PCR and proteomics.

    PubMed

    Deng, Shishan; Zhou, Hongying; Xiong, Ruohong; Lu, Youguang; Yan, Dazhong; Xing, Tianyong; Dong, Lihua; Tang, Enjie; Yang, Huijun

    2007-07-01

    The ubiquitin-proteasome system facilitates the degradation of damaged proteins and regulators of growth and stress response. Alterations in this proteolytic system are associated with a variety of human pathologies. By restriction fragment differential display polymerase chain reaction (RFDD-PCR) and matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF-TOF MS) based on two-dimensional polyacrylamide gel electrophoresis (2-DE), differentially expressed genes and proteins of ubiquitin specific proteases (USPs), proteasome subuinits (PSs) and ubiquitin protein ligase E3A (UBE3A) were analyzed between breast cancer and adjacent normal tissues. Some of them were further verified as over-expression by immunohistochemical stain. Five genes of proteasome subunits (PSs), including PSMB5, PSMD1, PSMD2, PSMD8 and PSMD11, four genes of USPs, including USP9X, USP9Y, USP10 and USP25, and ubiquitin protein ligase E3A (UBE3A) were over-expressed (>3-fold) in breast cancer tissue compared to adjacent normal tissue, and over-expression (>4-fold) of proteins of PSMA1 and SMT3A were observed in breast cancer tissue. PSMD8, PSMD11 and UBE3A were further verified as over-expression by immunohistochemical stain. The action of ubiquitin-proteasome system were obviously enhanced in breast cancer, and selectively intervention in action of ubiquitin-proteasome system may be a useful method of treating human breast cancer.

  15. Fibroadenoma - breast

    MedlinePlus

    ... provider if you notice: Any new breast lumps A breast lump that your provider has checked before that grows or changes Bruising on your breast for no reason Dimpled or wrinkled skin (like an orange) on your breast Nipple changes or nipple discharge

  16. Feature Extraction and Analysis of Breast Cancer Specimen

    NASA Astrophysics Data System (ADS)

    Bhattacharyya, Debnath; Robles, Rosslin John; Kim, Tai-Hoon; Bandyopadhyay, Samir Kumar

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

  17. Scaffold attachment factors SAFB1 and SAFB2: Innocent bystanders or critical players in breast tumorigenesis?

    PubMed

    Oesterreich, Steffi

    2003-11-01

    Scaffold attachment factor B1 (SAFB1) and SAFB2 are large, multifunctional proteins that have been implicated in numerous cellular processes including chromatin organization, transcriptional regulation, RNA splicing, and stress response. While the two homologous proteins show high similarity, and functional domains are highly conserved, evidence suggests that they also have unique properties. For example, SAFB2 can be found in both the nucleus and cytoplasm, whereas SAFB1 seems to be mainly localized in the nucleus. In breast cancer cells, SAFBs function as estrogen receptor corepressors and growth inhibitors. SAFB protein expression is lost in approximately 20% of breast cancers. Interestingly, the two genes reside in close proximity, oriented head-to-head, on chromosome 19p13, a locus which is frequently lost in clinical breast cancer specimens. Furthermore, SAFB1 mutations have been identified in breast tumors that were not present in adjacent normal tissue. The possibility that SAFB1 and SAFB2 are novel breast tumor suppressor genes, and how they might function in this role, are discussed.

  18. Endoscopic Breast Surgery in Treating Patients With Breast Cancer

    ClinicalTrials.gov

    2014-02-05

    Male Breast Cancer; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  19. miR-125b Acts as a Tumor Suppressor in Breast Tumorigenesis via Its Novel Direct Targets ENPEP, CK2-α, CCNJ, and MEGF9

    PubMed Central

    Feliciano, Andrea; Castellvi, Josep; Artero-Castro, Ana; Leal, Jose A.; Romagosa, Cleofé; Hernández-Losa, Javier; Peg, Vicente; Fabra, Angels; Vidal, Francisco; Kondoh, Hiroshi; Ramón y Cajal, Santiago; LLeonart, Matilde E.

    2013-01-01

    MicroRNAs (miRNAs) play important roles in diverse biological processes and are emerging as key regulators of tumorigenesis and tumor progression. To explore the dysregulation of miRNAs in breast cancer, a genome-wide expression profiling of 939 miRNAs was performed in 50 breast cancer patients. A total of 35 miRNAs were aberrantly expressed between breast cancer tissue and adjacent normal breast tissue and several novel miRNAs were identified as potential oncogenes or tumor suppressor miRNAs in breast tumorigenesis. miR-125b exhibited the largest decrease in expression. Enforced miR-125b expression in mammary cells decreased cell proliferation by inducing G2/M cell cycle arrest and reduced anchorage-independent cell growth of cells of mammary origin. miR-125b was found to perform its tumor suppressor function via the direct targeting of the 3’-UTRs of ENPEP, CK2-α, CCNJ, and MEGF9 mRNAs. Silencing these miR-125b targets mimicked the biological effects of miR-125b overexpression, confirming that they are modulated by miR-125b. Analysis of ENPEP, CK2-α, CCNJ, and MEGF9 protein expression in breast cancer patients revealed that they were overexpressed in 56%, 40–56%, 20%, and 32% of the tumors, respectively. The expression of ENPEP and CK2-α was inversely correlated with miR-125b expression in breast tumors, indicating the relevance of these potential oncogenic proteins in breast cancer patients. Our results support a prognostic role for CK2-α, whose expression may help clinicians predict breast tumor aggressiveness. In particular, our results show that restoration of miR-125b expression or knockdown of ENPEP, CK2-α, CCNJ, or MEGF9 may provide novel approaches for the treatment of breast cancer. PMID:24098452

  20. Histomorphometric evidence for osteoclast-mediated bone resorption in metastatic breast cancer.

    PubMed

    Taube, T; Elomaa, I; Blomqvist, C; Beneton, M N; Kanis, J A

    1994-01-01

    We studied bone biopsies from 65 normocalcaemic women with breast cancer and predominantly osteolytic bone metastases in order to examine the pathophysiology of bone destruction in metastatic bone disease. Quantitative histomorphometric measurements were made at sites of tumour involvement, at sites adjacent to tumour tissue and at sites distant from tumour tissue. There were no significant differences in bone volume or in indices of bone resorption or formation between biopsies taken from sites distant from tumour and the controls. Bone resorption, as judged by eroded surface, increased progressively from bone distant from tumour to tumour-laden bone. The number of osteoclasts was significantly increased in bone immediately adjacent to tumour and within metastases. There was no decrease in the ratio of osteoclast to eroded surface in breast cancer compared to controls suggesting that increased resorption in breast cancer was mainly osteoclast mediated and locally activated by the tumour. Two thirds of the biopsies taken from tumour involved regions showed osteosclerosis with woven bone formation. The volume of the pre-existing lamellar trabecular bone was lower than normal in 75% of these biopsies, suggesting that bone resorption must have been increased before the onset of woven bone formation. Since all patients were receiving hormonal treatment or chemotherapy, it is likely that osteosclerosis at sites of previous resorption mainly resulted from the basic cancer treatment as a sign of response to treatment. Osteoclastic bone resorption was, however, not completely inhibited by the active cancer treatment.

  1. Imaging dose in breast radiotherapy: does breast size affect the dose to the organs at risk and the risk of secondary cancer to the contralateral breast?

    SciTech Connect

    Batumalai, Vikneswary; Quinn, Alexandra; Jameson, Michael; Delaney, Geoff; Holloway, Lois

    2015-03-15

    Correct target positioning is crucial for accurate dose delivery in breast radiotherapy resulting in utilisation of daily imaging. However, the radiation dose from daily imaging is associated with increased probability of secondary induced cancer. The aim of this study was to quantify doses associated with three imaging modalities and investigate the correlation of dose and varying breast size in breast radiotherapy. Planning computed tomography (CT) data sets of 30 breast cancer patients were utilised to simulate the dose received by various organs from a megavoltage computed tomography (MV-CT), megavoltage electronic portal image (MV-EPI) and megavoltage cone-beam computed tomography (MV-CBCT). The mean dose to organs adjacent to the target volume (contralateral breast, lungs, spinal cord and heart) were analysed. Pearson correlation analysis was performed to determine the relationship between imaging dose and primary breast volume and the lifetime attributable risk (LAR) of induced secondary cancer was calculated for the contralateral breast. The highest contralateral breast mean dose was from the MV-CBCT (1.79 Gy), followed by MV-EPI (0.22 Gy) and MV-CT (0.11 Gy). A similar trend was found for all organs at risk (OAR) analysed. The primary breast volume inversely correlated with the contralateral breast dose for all three imaging modalities. As the primary breast volume increases, the likelihood of a patient developing a radiation-induced secondary cancer to the contralateral breast decreases. MV-CBCT showed a stronger relationship between breast size and LAR of developing a radiation-induced contralateral breast cancer in comparison with the MV-CT and MV-EPI. For breast patients, imaging dose to OAR depends on imaging modality and treated breast size. When considering the use of imaging during breast radiotherapy, the patient's breast size and contralateral breast dose should be taken into account.

  2. Oncoplastic techniques in breast surgery for special therapeutic problems

    PubMed Central

    Lertsithichai, Panuwat; Sukarayothin, Thongchai; Leesombatpaiboon, Monchai; Supsamutchai, Chairat; Kongdan, Youwanush

    2016-01-01

    Resection of large tumors can be challenging, from the view point of breast preservation. Oncoplastic techniques are a valuable component of breast surgery in patients with large breast tumors who desire breast preservation. These techniques have been shown to be oncologically safe, while maintaining acceptable breast cosmesis. For locally advanced or recurrent breast cancers, the goals of surgery include local disease control and palliation of clinical symptoms. Oncoplastic surgery is also effective and oncologically safe in these situations. The need to completely remove all foci of cancers with adequate surgical margins often requires the displacement of adjacent or distant skin and soft tissue to cover the resulting soft tissue defect. Sometimes doing so can be cosmetically pleasing as well. In this article we present three special therapeutic problems in three distinct conditions, all resolved with oncoplastic techniques: the benign breast condition, malignant breast condition, and the palliative setting. PMID:26855912

  3. Oncoplastic techniques in breast surgery for special therapeutic problems.

    PubMed

    Chirappapha, Prakasit; Lertsithichai, Panuwat; Sukarayothin, Thongchai; Leesombatpaiboon, Monchai; Supsamutchai, Chairat; Kongdan, Youwanush

    2016-02-01

    Resection of large tumors can be challenging, from the view point of breast preservation. Oncoplastic techniques are a valuable component of breast surgery in patients with large breast tumors who desire breast preservation. These techniques have been shown to be oncologically safe, while maintaining acceptable breast cosmesis. For locally advanced or recurrent breast cancers, the goals of surgery include local disease control and palliation of clinical symptoms. Oncoplastic surgery is also effective and oncologically safe in these situations. The need to completely remove all foci of cancers with adequate surgical margins often requires the displacement of adjacent or distant skin and soft tissue to cover the resulting soft tissue defect. Sometimes doing so can be cosmetically pleasing as well. In this article we present three special therapeutic problems in three distinct conditions, all resolved with oncoplastic techniques: the benign breast condition, malignant breast condition, and the palliative setting. PMID:26855912

  4. Abundant NDRG2 Expression Is Associated with Aggressiveness and Unfavorable Patients’ Outcome in Basal-Like Breast Cancer

    PubMed Central

    Gasthaus, Janina; Tiedemann, Janina; Mijnes, Jolein; Heide, Timon; Braunschweig, Till; Knüchel, Ruth; Dahl, Edgar

    2016-01-01

    NDRG2, a member of the N-myc downstream-regulated gene family, is thought to be a putative tumor suppressor gene with promising clinical impact in breast cancer. Since breast cancer comprises heterogeneous intrinsic subtypes with distinct clinical outcomes we investigated the pivotal role of NDRG2 in basal-type breast cancers. Based on subtype classified tumor (n = 45) and adjacent normal tissues (n = 17) we examined NDRG2 mRNA expression and CpG-hypermethylation, whose significance was further validated by independent data sets from The Cancer Genome Atlas (TCGA). In addition, NDRG2 protein expression was evaluated immunohistochemically using a tissue micro array (TMA, n = 211). In vitro, we investigated phenotypic effects caused by NDRG2 silencing in the basal A-like HCC1806 as well as NDRG2 over-expression in basal A-like BT20 compared to luminal-type MCF7 breast cancer cells. Our tissue collections demonstrated an overall low NDRG2 mRNA expression in breast cancer subtypes compared to normal breast tissue in line with an increased CpG-hypermethylation in breast cancer tissue. Independent TCGA data sets verified a significant (P<0.001) expression loss of NDRG2 in breast tumors. Of interest, basal-like tumors more frequently retained abundant NDRG2 expression concordant with a lower CpG-hypermethylation. Unexpectedly, basal-like breast cancer revealed an association of NDRG2 expression with unfavorable patients’ outcome. In line with this observation, in vitro experiments demonstrated reduced proliferation and migration rates (~20%) in HCC1806 cells following NDRG2 silencing. In contrast, NDRG2 over-expressing luminal-type MCF7 cells demonstrated a 26% decreased proliferation rate. Until now, this is the first study investigating the putative role of NDRG2 in depth in basal-type breast cancer. Our data indicate that the described putative tumor suppressive function of NDRG2 may be confined to luminal- and basal B-type breast cancers. PMID:27400234

  5. Breast Cancer

    MedlinePlus

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

  6. On the time-course of adjacent and non-adjacent transposed-letter priming

    PubMed Central

    Ktori, Maria; Kingma, Brechtsje; Hannagan, Thomas; Holcomb, Phillip J.; Grainger, Jonathan

    2014-01-01

    We compared effects of adjacent (e.g., atricle-ARTICLE) and non-adjacent (e.g., actirle-ARTICLE) transposed-letter (TL) primes in an ERP study using the sandwich priming technique. TL priming was measured relative to the standard double-substitution condition. We found significantly stronger priming effects for adjacent transpositions than non-adjacent transpositions (with 2 intervening letters) in behavioral responses (lexical decision latencies), and the adjacent priming effects emerged earlier in the ERP signal, at around 200 ms post-target onset. Non-adjacent priming effects emerged about 50 ms later and were short-lived, being significant only in the 250-300 ms time-window. Adjacent transpositions on the other hand continued to produce priming in the N400 time-window (300-500 ms post-target onset). This qualitatively different pattern of priming effects for adjacent and non-adjacent transpositions is discussed in the light of different accounts of letter transposition effects, and the utility of drawing a distinction between positional flexibility and positional noise. PMID:25364497

  7. The diagnosis and management of pre-invasive breast disease: Promise of new technologies in understanding pre-invasive breast lesions

    PubMed Central

    Jeffrey, Stefanie S; Pollack, Jonathan R

    2003-01-01

    Array-based comparative genomic hybridization, RNA expression profiling, and proteomic analyses are new molecular technologies used to study breast cancer. Invasive breast cancers were originally evaluated because they provided ample quantities of DNA, RNA, and protein. The application of these technologies to pre-invasive breast lesions is discussed, including methods that facilitate their implementation. Data indicate that atypical ductal hyperplasia and ductal carcinoma in situ are precursor lesions molecularly similar to adjacent invasive breast cancer. It is expected that molecular technologies will identify breast tissue at risk for the development of unfavorable subtypes of invasive breast cancer and reveal strategies for targeted chemoprevention or eradication. PMID:14580250

  8. MINARETS WILDERNESS AND ADJACENT AREAS, CALIFORNIA.

    USGS Publications Warehouse

    Huber, N. King; Thurber, Horace K.

    1984-01-01

    A mineral survey of the Minarets Wilderness and adjacent areas in the central Sierra Nevada, California was conducted. The results of the survey indicate that the study area has a substantiated resource potential for small deposits of copper, silver, zinc, lead, and iron, and a probable mineral-resource potential for molybdenum. No energy-resource potential was identified in the study.

  9. 46 CFR 148.445 - Adjacent spaces.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES CARRIAGE OF BULK SOLID MATERIALS... transporting a material that Table 148.10 of this part associates with a reference to this section, the following requirements must be met: (a) Each space adjacent to a cargo hold must be ventilated by...

  10. 46 CFR 148.445 - Adjacent spaces.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES CARRIAGE OF BULK SOLID MATERIALS... transporting a material that Table 148.10 of this part associates with a reference to this section, the following requirements must be met: (a) Each space adjacent to a cargo hold must be ventilated by...

  11. 46 CFR 148.445 - Adjacent spaces.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES CARRIAGE OF BULK SOLID MATERIALS... transporting a material that Table 148.10 of this part associates with a reference to this section, the following requirements must be met: (a) Each space adjacent to a cargo hold must be ventilated by...

  12. 46 CFR 148.445 - Adjacent spaces.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES CARRIAGE OF BULK SOLID MATERIALS... transporting a material that Table 148.10 of this part associates with a reference to this section, the following requirements must be met: (a) Each space adjacent to a cargo hold must be ventilated by...

  13. Breast Cancer Prevention

    MedlinePlus

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

  14. Types of Breast Cancers

    MedlinePlus

    ... the key statistics about breast cancer? Types of breast cancers Breast cancer can be separated into different types ... than invasive ductal carcinoma. Less common types of breast cancer Inflammatory breast cancer This uncommon type of invasive ...

  15. Breast self-exam

    MedlinePlus

    Self-examination of the breast; BSE; Breast cancer - BSE; Breast cancer screening - self exam ... American Cancer Society. Recommendations for early breast cancer detection in women without breast symptoms. Revised October 20, ... ...

  16. Human Breast Cancer Invasion and Aggression Correlates with ECM Stiffening and Immune Cell Infiltration

    PubMed Central

    Acerbi, I; Cassereau, L; Dean, I; Shi, Q; Au, A; Park, C; Chen, YY; Liphardt, J; Hwang, ES; Weaver, VM

    2015-01-01

    Tumors are stiff and data suggest that the extracellular matrix stiffening that correlates with experimental mammary malignancy drives tumor invasion and metastasis. Nevertheless, the relationship between tissue and extracellular matrix stiffness and human breast cancer progression and aggression remains unclear. We undertook a biophysical and biochemical assessment of stromal-epithelial interactions in noninvasive, invasive and normal adjacent human breast tissue and in breast cancers of increasingly aggressive subtype. Our analysis revealed that human breast cancer transformation is accompanied by an incremental increase in collagen deposition and a progressive linearization and thickening of interstitial collagen. The linearization of collagen was visualized as an overall increase in tissue birefringence and was most striking at the invasive front of the tumor where the stiffness of the stroma and cellular mechanosignaling were the highest. Amongst breast cancer subtypes we found that the stroma at the invasive region of the more aggressive Basal-like and Her2 tumor subtypes was the most heterogeneous and the stiffest when compared to the less aggressive Luminal A and B subtypes. Intriguingly, we quantified the greatest number of infiltrating macrophages and the highest level of TGF beta signaling within the cells at the invasive front. We also established that stroma stiffness and the level of cellular TGF beta signaling positively correlated with each other and with the number of infiltrating tumor-activated, macrophages, which was highest in the more aggressive tumor subtypes. These findings indicate that human breast cancer progression and aggression, collagen linearization and stromal stiffening are linked and implicate tissue inflammation and TGF beta. PMID:25959051

  17. Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration.

    PubMed

    Acerbi, I; Cassereau, L; Dean, I; Shi, Q; Au, A; Park, C; Chen, Y Y; Liphardt, J; Hwang, E S; Weaver, V M

    2015-10-01

    Tumors are stiff and data suggest that the extracellular matrix stiffening that correlates with experimental mammary malignancy drives tumor invasion and metastasis. Nevertheless, the relationship between tissue and extracellular matrix stiffness and human breast cancer progression and aggression remains unclear. We undertook a biophysical and biochemical assessment of stromal-epithelial interactions in noninvasive, invasive and normal adjacent human breast tissue and in breast cancers of increasingly aggressive subtype. Our analysis revealed that human breast cancer transformation is accompanied by an incremental increase in collagen deposition and a progressive linearization and thickening of interstitial collagen. The linearization of collagen was visualized as an overall increase in tissue birefringence and was most striking at the invasive front of the tumor where the stiffness of the stroma and cellular mechanosignaling were the highest. Amongst breast cancer subtypes we found that the stroma at the invasive region of the more aggressive Basal-like and Her2 tumor subtypes was the most heterogeneous and the stiffest when compared to the less aggressive luminal A and B subtypes. Intriguingly, we quantified the greatest number of infiltrating macrophages and the highest level of TGF beta signaling within the cells at the invasive front. We also established that stroma stiffness and the level of cellular TGF beta signaling positively correlated with each other and with the number of infiltrating tumor-activated macrophages, which was highest in the more aggressive tumor subtypes. These findings indicate that human breast cancer progression and aggression, collagen linearization and stromal stiffening are linked and implicate tissue inflammation and TGF beta. PMID:25959051

  18. Aromatase and cyclooxygenases: enzymes in breast cancer.

    PubMed

    Brueggemeier, Robert W; Richards, Jeanette A; Petrel, Trevor A

    2003-09-01

    Aromatase (estrogen synthase) is the cytochrome P450 enzyme complex that converts C19 androgens to C18 estrogens. Aromatase activity has been demonstrated in breast tissue in vitro, and expression of aromatase is highest in or near breast tumor sites. Thus, local regulation of aromatase by both endogenous factors as well as exogenous medicinal agents will influence the levels of estrogen available for breast cancer growth. The prostaglandin PGE2 increases intracellular cAMP levels and stimulates estrogen biosynthesis, and previous studies in our laboratories have shown a strong linear association between aromatase (CYP19) expression and expression of the cyclooxygenases (COX-1 and COX-2) in breast cancer specimens. To further investigate the pathways regulating COX and CYP19 gene expression, studies were performed in normal breast stromal cells, in breast cancer cells from patients, and in breast cancer cell lines using selective pharmacological agents. Enhanced COX enzyme levels results in increased production of prostaglandins, such as PGE2. This prostaglandin increased aromatase activity in breast stromal cells, and studies with selective agonists and antagonists showed that this regulation of signaling pathways occurs through the EP1 and EP2 receptor subtypes. COX-2 gene expression was enhanced in breast cancer cell lines by ligands for the various peroxisome proliferator-activated receptors (PPARs), and differential regulation was observed between hormone-dependent and -independent breast cancer cells. Thus, the regulation of both enzymes in breast cancer involves complex paracrine interactions, resulting in significant consequences on the pathogenesis of breast cancer. PMID:14623550

  19. TFRC and ACTB as the best reference genes to quantify Urokinase Plasminogen Activator in breast cancer

    PubMed Central

    2011-01-01

    Background Biomedical researchers have long looked for ways to diagnose and treat cancer patients at the early stages through biomarkers. Although conventional techniques are routinely applied in the detection of biomarkers, attitudes towards using Real-Time PCR techniques in detection of many biomarkers are increasing. Normalization of quantitative Real-Time PCR is necessary to validate non-biological alteration occurring during the steps of RNA quantification. Selection of variably expressed housekeeping genes (HKs) will affect the validity of the data. The aim of the present study was to identify uniformly expressed housekeeping genes in order to use in the breast cancer gene expression studies. Urokinase Plasminogen Activator was used as a gene of interest. Findings The expression of six HKs (TFRC, GUSB, GAPDH, ACTB, HPRT1 and RPLP0) was investigated using geNorm and NormFinder softwares in forty breast tumor, four normal and eight adjacent tissues. RPLP0 and GAPDH revealed maximum M value, while TFRC demonstrated lowest M value. Conclusions In the present study the most and the least stable genes were TFRC and RPLP0 respectively. TFRC and ACTB were verified as the best combination of two genes for breast cancer quantification. The result of this study shows that in each gene expression analysis HKs selection should be done based on experiment conditions. PMID:21702980

  20. Quantitative DNA hypomethylation of ligand Jagged1 and receptor Notch1 signifies occurrence and progression of breast carcinoma

    PubMed Central

    Cao, Yuwen; Li, Yixiao; Zhang, Na; Hu, Jianming; Yin, Liang; Pan, Zemin; Li, Yucong; Du, Xiaoming; Zhang, Wenjie; Li, Feng

    2015-01-01

    Methylation alterations of Jagged1 and Notch1 genes have been reported in non-tumor lesions and a few cancers. However, methylation profiles of Jagged1 promoter and Notch1 exon25 in breast cancer and matched normal tissue and the association of methylation with clinicopathological characteristics still remain unclear. To explore the potential effects of aberrant DNA methylation of Jagged1 and Notch1 on occurrence and progression of breast cancer, we detected the quantitative DNA methylation of Jagged1 and Notch1 in 73 breast cancer (BC) and 20 adjacent normal breast tissues (ANBT) by using MassARRAY spectrometry. The methylation level of overall and majority individual CpG sites of the two genes were synergistically significantly lower in BC than in ANBT. The overall hypomethylation of the two genes, particularly of Jagged1 CpG_8.9.10 and Notch1 CpG_14.15.16 in primary tumors, were markedly associated with lymph node metastasis, advanced stage and high grade. The protein expressions of the both genes were examined by immunohistochemical staining in same cohorts. The expression was significantly inverse correlation with methylation. The two proteins in primary tumor were synergistically up-regulated and dramatically related to lymph node metastasis, advanced stage and high grade. Our findings suggest that the synergetic hypomethylation of Jagged1 and Notch1 genes, especially of Jagged1 CpG_8.9.10 and Notch1 CpG_14.15.16, may involve tumorigenesis and development of breast cancer. The negative relationship between methylation and expression indicates methylation role for expression regulation. The synergetic overexpression of the two proteins further indicates the effects on occurrence and progression of breast cancer. PMID:26175933

  1. Quantitative DNA hypomethylation of ligand Jagged1 and receptor Notch1 signifies occurrence and progression of breast carcinoma

    PubMed Central

    Cao, Yuwen; Li, Yixiao; Zhang, Na; Hu, Jianming; Yin, Liang; Pan, Zemin; Li, Yucong; Du, Xiaoming; Zhang, Wenjie; Li, Feng

    2015-01-01

    Methylation alterations of Jagged1 and Notch1 genes have been reported in non-tumor lesions and a few cancers. However, methylation profiles of Jagged1 promoter and Notch1 exon25 in breast cancer and matched normal tissue and the association of methylation with clinicopathological characteristics still remain unclear. To explore the potential effects of aberrant DNA methylation of Jagged1 and Notch1 on occurrence and progression of breast cancer, we detected the quantitative DNA methylation of Jagged1 and Notch1 in 73 breast cancer (BC) and 20 adjacent normal breast tissues (ANBT) by using MassARRAY spectrometry. The methylation level of overall and majority individual CpG sites of the two genes were synergistically significantly lower in BC than in ANBT. The overall hypomethylation of the two genes, particularly of Jagged1 CpG_8.9.10 and Notch1 CpG_14.15.16 in primary tumors, were markedly associated with lymph node metastasis, advanced stage and high grade. The protein expressions of the both genes were examined by immunohistochemical staining in same cohorts. The expression was significantly inverse correlation with methylation. The two proteins in primary tumor were synergistically up-regulated and dramatically related to lymph node metastasis, advanced stage and high grade. Our findings suggest that the synergetic hypomethylation of Jagged1 and Notch1 genes, especially of Jagged1 CpG_8.9.10 and Notch1 CpG_14.15.16, may involve tumorigenesis and development of breast cancer. The negative relationship between methylation and expression indicates methylation role for expression regulation. The synergetic overexpression of the two proteins further indicates the effects on occurrence and progression of breast cancer. PMID:26269752

  2. Fast microcalcification detection in ultrasound images using image enhancement and threshold adjacency statistics

    NASA Astrophysics Data System (ADS)

    Cho, Baek Hwan; Chang, Chuho; Lee, Jong-Ha; Ko, Eun Young; Seong, Yeong Kyeong; Woo, Kyoung-Gu

    2013-02-01

    The existence of microcalcifications (MCs) is an important marker of malignancy in breast cancer. In spite of the benefits in mass detection for dense breasts, ultrasonography is believed that it might not reliably detect MCs. For computer aided diagnosis systems, however, accurate detection of MCs has the possibility of improving the performance in both Breast Imaging-Reporting and Data System (BI-RADS) lexicon description for calcifications and malignancy classification. We propose a new efficient and effective method for MC detection using image enhancement and threshold adjacency statistics (TAS). The main idea of TAS is to threshold an image and to count the number of white pixels with a given number of adjacent white pixels. Our contribution is to adopt TAS features and apply image enhancement to facilitate MC detection in ultrasound images. We employed fuzzy logic, tophat filter, and texture filter to enhance images for MCs. Using a total of 591 images, the classification accuracy of the proposed method in MC detection showed 82.75%, which is comparable to that of Haralick texture features (81.38%). When combined, the performance was as high as 85.11%. In addition, our method also showed the ability in mass classification when combined with existing features. In conclusion, the proposed method exploiting image enhancement and TAS features has the potential to deal with MC detection in ultrasound images efficiently and extend to the real-time localization and visualization of MCs.

  3. The MYC oncogene in breast cancer progression: from benign epithelium to invasive carcinoma.

    PubMed

    Corzo, Cristina; Corominas, Josep M; Tusquets, Ignacio; Salido, Marta; Bellet, Meritxell; Fabregat, Xavier; Serrano, Sergio; Solé, Francesc

    2006-03-01

    One hypothesis for breast cancer development suggests that breast carcinogenesis involves a progression of events leading from benign epithelium to hyperplasia (with or without atypia) to carcinoma in situ and then invasive carcinoma. The MYC gene (alias c-Myc) is a transcriptional regulator whose expression is strongly associated with cell proliferation and cell differentiation. The present study is a descriptive analysis of MYC status throughout the hypothesized stages of invasive ductal carcinoma progression. A tissue microarray (TMA) was constructed including representative selected areas (normal cells, hyperplasia, in situ carcinoma, and invasive carcinoma) from each of 15 patients. Fluorescence in situ hybridization (FISH) with the LSI c-MYC/CEN8/IgH probe was performed. Two cases displayed MYC amplification (13%), showing this amplification only in the invasive carcinoma zones selected. Five cases displayed polysomy of chromosome 8 (33%), detected only in ductal in situ and invasive zones selected. Benign lesions and normal adjacent cells were classified as normal. None of the hyperplasia specimens and normal specimens analyzed showed any alterations in MYC status or any aneusomies of chromosome 8. The presence of MYC amplification only in invasive cells suggests that the finding of MYC amplification could reflect an advanced tumor progression.

  4. The Thermomagnetic Instability in Superconducting Films with Adjacent Metal Layer

    NASA Astrophysics Data System (ADS)

    Vestgården, J. I.; Galperin, Y. M.; Johansen, T. H.

    2013-12-01

    Dendritic flux avalanches is a frequently encountered consequence of the thermomagnetic instability in type-II superconducting films. The avalanches, which are potentially harmful for superconductor-based devices, can be suppressed by an adjacent normal metal layer, even when the two layers are not in thermal contact. The suppression of the avalanches in this case is due to so-called magnetic braking, caused by eddy currents generated in the metal layer by propagating magnetic flux. We develop a theory of magnetic braking by analyzing coupled electrodynamics and heat flow in a superconductor-normal metal bilayer. The equations are solved by linearization and by numerical simulation of the avalanche dynamics. We find that in an uncoated superconductor, even a uniform thermomagnetic instability can develop into a dendritic flux avalanche. The mechanism is that a small non-uniformity caused by the electromagnetic non-locality induces a flux-flow hot spot at a random position. The hot spot quickly develops into a finger, which at high speeds penetrates into the superconductor, forming a branching structure. Magnetic braking slows the avalanches, and if the normal metal conductivity is sufficiently high, it can suppress the formation of the dendritic structure. During avalanches, the braking by the normal metal layer prevents the temperature from exceeding the transition temperature of the superconductor. Analytical criteria for the instability threshold are developed using the linear stability analysis. The criteria are found to match quantitatively the instability onsets obtained in simulations.

  5. Expression of integrin-binding protein Nischarin in metastatic breast cancer

    PubMed Central

    CHEN, JIE; FENG, WEI-LIANG; MO, WEN-JU; DING, XIAO-WEN; XIE, SHANG-NAO

    2015-01-01

    The present study aimed to investigate the expression of Nischarin protein in primary breast cancer (PBC), and to evaluate its role in tumor metastasis. Paired specimens of breast cancer tissues and adjacent normal tissues were surgically obtained from 60 patients with PBC at the Zhejiang Cancer Hospital (Hangzhou, China). Nischarin protein concentrations were determined by an ELISA assay. Breast cancer tissues exhibited a significantly lower concentration of Nischarin (5.86±3.19 ng/ml) compared with that of the adjacent noncancerous tissues (9.25±3.65 ng/ml; P<0.001). Furthermore, cancer tissue from patients with lymph node metastasis had significantly lower levels of Nischarin protein (4.69±2.40 ng/ml) than those of patients without lymph node metastasis (7.04±3.47 ng/ml; P=0.004). There was no significant difference in Nischarin protein expression levels between patients with grade I, II or III PBC (grade I, 5.44±3.57 ng/ml; grade II, 6.42±3.85 ng/ml and grade III, 5.10±1.18 ng/ml; P=0.765). The significant differences in the expression of Nischarin between: i) Cancer tissue and noncancerous tissue and ii) patients with and without lymph node metastasis, suggested that Nischarin may have a significant role in tumor occurrence and metastasis of breast cancer. Nischarin expression may therefore be used as a marker to predict the invasiveness and metastasis of PBC. PMID:25695373

  6. What Is Breast in the Bone?

    PubMed Central

    Shemanko, Carrie S.; Cong, Yingying; Forsyth, Amanda

    2016-01-01

    The normal developmental program that prolactin generates in the mammary gland is usurped in the cancerous process and can be used out of its normal cellular context at a site of secondary metastasis. Prolactin is a pleiotropic peptide hormone and cytokine that is secreted from the pituitary gland, as well as from normal and cancerous breast cells. Experimental and epidemiologic data suggest that prolactin is associated with mammary gland development, and also the increased risk of breast tumors and metastatic disease in postmenopausal women. Breast cancer spreads to the bone in approximately 70% of cases with advanced breast cancer. Despite treatment, new bone metastases will still occur in 30%–50% of patients. Only 20% of patients with bone metastases survive five years after the diagnosis of bone metastasis. The breast cancer cells in the bone microenvironment release soluble factors that engage osteoclasts and/or osteoblasts and result in bone breakdown. The breakdown of the bone matrix, in turn, enhances the proliferation of the cancer cells, creating a vicious cycle. Recently, it was shown that prolactin accelerated the breast cancer cell-mediated osteoclast differentiation and bone breakdown by the regulation of breast cancer-secreted proteins. Interestingly, prolactin has the potential to affect multiple proteins that are involved in both breast development and likely bone metastasis, as well. Prolactin has normal bone homeostatic roles and, combined with the natural “recycling” of proteins in different tissues that can be used for breast development and function, or in bone function, increases the impact of prolactin signaling in breast cancer bone metastases. Thus, this review will focus on the role of prolactin in breast development, bone homeostasis and in breast cancer to bone metastases, covering the molecular aspects of the vicious cycle. PMID:27782069

  7. Adjacent Segment Pathology after Lumbar Spinal Fusion.

    PubMed

    Lee, Jae Chul; Choi, Sung-Woo

    2015-10-01

    One of the major clinical issues encountered after lumbar spinal fusion is the development of adjacent segment pathology (ASP) caused by increased mechanical stress at adjacent segments, and resulting in various radiographic changes and clinical symptoms. This condition may require surgical intervention. The incidence of ASP varies with both the definition and methodology adopted in individual studies; various risk factors for this condition have been identified, although a significant controversy still exists regarding their significance. Motion-preserving devices have been developed, and some studies have shown their efficacy of preventing ASP. Surgeons should be aware of the risk factors of ASP when planning a surgery, and accordingly counsel their patients preoperatively. PMID:26435804

  8. Adjacent Segment Pathology after Lumbar Spinal Fusion

    PubMed Central

    Lee, Jae Chul

    2015-01-01

    One of the major clinical issues encountered after lumbar spinal fusion is the development of adjacent segment pathology (ASP) caused by increased mechanical stress at adjacent segments, and resulting in various radiographic changes and clinical symptoms. This condition may require surgical intervention. The incidence of ASP varies with both the definition and methodology adopted in individual studies; various risk factors for this condition have been identified, although a significant controversy still exists regarding their significance. Motion-preserving devices have been developed, and some studies have shown their efficacy of preventing ASP. Surgeons should be aware of the risk factors of ASP when planning a surgery, and accordingly counsel their patients preoperatively. PMID:26435804

  9. Adjacent Segment Pathology after Anterior Cervical Fusion.

    PubMed

    Chung, Jae Yoon; Park, Jong-Beom; Seo, Hyoung-Yeon; Kim, Sung Kyu

    2016-06-01

    Anterior cervical fusion has become a standard of care for numerous pathologic conditions of the cervical spine. However, subsequent development of clinically significant disc disease at levels adjacent to fused discs is a serious long-term complication of this procedure. As more patients live longer after surgery, it is foreseeable that adjacent segment pathology (ASP) will develop in increasing numbers of patients. Also, ASP has been studied more intensively with the recent popularity of motion preservation technologies like total disc arthroplasty. The true nature and scope of ASP remains poorly understood. The etiology of ASP is most likely multifactorial. Various factors including altered biomechanical stresses, surgical disruption of soft tissue and the natural history of cervical disc disease contribute to the development of ASP. General factors associated with disc degeneration including gender, age, smoking and sports may play a role in the development of ASP. Postoperative sagittal alignment and type of surgery are also considered potential causes of ASP. Therefore, a spine surgeon must be particularly careful to avoid unnecessary disruption of the musculoligamentous structures, reduced risk of direct injury to the disc during dissection and maintain a safe margin between the plate edge and adjacent vertebrae during anterior cervical fusion.

  10. Adjacent Segment Pathology after Anterior Cervical Fusion

    PubMed Central

    Chung, Jae Yoon; Park, Jong-Beom; Seo, Hyoung-Yeon

    2016-01-01

    Anterior cervical fusion has become a standard of care for numerous pathologic conditions of the cervical spine. However, subsequent development of clinically significant disc disease at levels adjacent to fused discs is a serious long-term complication of this procedure. As more patients live longer after surgery, it is foreseeable that adjacent segment pathology (ASP) will develop in increasing numbers of patients. Also, ASP has been studied more intensively with the recent popularity of motion preservation technologies like total disc arthroplasty. The true nature and scope of ASP remains poorly understood. The etiology of ASP is most likely multifactorial. Various factors including altered biomechanical stresses, surgical disruption of soft tissue and the natural history of cervical disc disease contribute to the development of ASP. General factors associated with disc degeneration including gender, age, smoking and sports may play a role in the development of ASP. Postoperative sagittal alignment and type of surgery are also considered potential causes of ASP. Therefore, a spine surgeon must be particularly careful to avoid unnecessary disruption of the musculoligamentous structures, reduced risk of direct injury to the disc during dissection and maintain a safe margin between the plate edge and adjacent vertebrae during anterior cervical fusion. PMID:27340541

  11. Targeted expression of miR-34a using the T-VISA system suppresses breast cancer cell growth and invasion.

    PubMed

    Li, Laisheng; Xie, Xinhua; Luo, Jinmei; Liu, Min; Xi, Shaoyan; Guo, Jiaoli; Kong, Yanan; Wu, Minqing; Gao, Jie; Xie, Zeming; Tang, Jun; Wang, Xi; Wei, Weidong; Yang, Mingtian; Hung, Mien-Chie; Xie, Xiaoming

    2012-12-01

    Recurrence and metastasis result in a poor prognosis for breast cancer patients. Recent studies have demonstrated that microRNAs (miRNAs) play vital roles in the development and metastasis of breast cancer. In this study, we investigated the therapeutic potential of miR-34a in breast cancer. We found that miR-34a is downregulated in breast cancer cell lines and tissues, compared with normal cell lines and the adjacent nontumor tissues, respectively. To explore the therapeutic potential of miR-34a, we designed a targeted miR-34a expression plasmid (T-VISA-miR-34a) using the T-VISA system, and evaluated its antitumor effects, efficacy, mechanism of action, and systemic toxicity. T-VISA-miR-34a induced robust, persistent expression of miR-34a, and dramatically suppressed breast cancer cell growth, migration, and invasion in vitro by downregulating the protein expression levels of the miR-34a target genes E2F3, CD44, and SIRT1. In an orthotopic mouse model of breast cancer, intravenous injection of T-VISA-miR-34a:liposomal complex nanoparticles significantly inhibited tumor growth, prolonged survival, and did not induce systemic toxicity. In conclusion, T-VISA-miR-34a lead to robust, specific overexpression of miR-34a in breast cancer cells and induced potent antitumor effects in vitro and in vivo. T-VISA-miR-34a may provide a potentially useful, specific, and safe-targeted therapeutic approach for breast cancer.

  12. Zinc-Finger Protein 545 Inhibits Cell Proliferation as a Tumor Suppressor through Inducing Apoptosis and is Disrupted by Promoter Methylation in Breast Cancer

    PubMed Central

    Luo, Xinrong; Li, Chunhong; Li, Qianqian; Peng, Weiyan; Li, Lili; Li, Shuman; Wang, Zhenyu; Tang, Liping; Ren, Guosheng; Tao, Qian

    2014-01-01

    Krüppel-associated box-containing zinc finger proteins (KRAP-ZFPs) are well recognized as key regulators of transcription, which play a crucial role in the regulation of cell proliferation, differentiation, apoptosis and tumorigenesis. We previously identified a KRAP-ZFP protein ZNF545 acting as a tumor suppressor involved in tumor pathogenesis. However, its expression and biological function in breast cancer remain elusive. In this study, we found that ZNF545 was frequently downregulated in estrogen receptor-positive (ER+), progesterone receptor-positive (PR+) and human epidermal growth factor receptor 2-negative (HER2−) breast tumor tissues compared with paired adjacent non-tumor tissues. We further examined its expression and methylation in breast cancer cell lines by semi-quantitative RT-PCR and methylation-specific PCR. We found that ZNF545 was silenced by promoter methylation in MCF7 cell line, and its expression could be restored by demethylation, concomitant with increased unmethylated alleles. ZNF545 methylation was detected in 29% of breast tumor tissues, but not in normal breast tissues, suggesting tumor-specific methylation of ZNF545 in breast cancer. Ectopic expression of ZNF545 in MCF7 cells inhibited cell proliferation through inducing cell cycle G0/G1 arrest and apoptosis, thus as a tumor suppressor. Moreover, ZNF545 upregulated mRNA and protein levels of c-Jun/AP1, BAX, p53 and Caspase 3. Taken together, these results demonstrate that ZNF545 inhibits breast tumor cell proliferation through inducing apoptosis and is disrupted by promoter methylation in breast cancer. PMID:25360542

  13. Transillumination breast spectroscopy (TIBS): a biomarker of breast tissue density

    NASA Astrophysics Data System (ADS)

    Blackmore, Kristina M.; Knight, Julia A.; Jong, Roberta; Lilge, Lothar

    2005-08-01

    A primary goal of preventive oncology is the identification of women at increased risk for breast cancer who would benefit most from risk reducing interventions. An established physical risk assessment technique is the use of mammography to quantify the dense tissue content of the breast. Women with a majority of the breast occupied by dense tissue are at four to six times greater risk of breast cancer than women with the least density. The main drawback of mammography is that it requires exposure to ionising radiation and there are concerns regarding use in young women. Another potential physical risk assessment is Transillumination Breast Spectroscopy (TIBS). TIBS uses non-ionizing optical radiation to measure bulk tissue properties and thus is applicable to women of any age. This study examines the feasibility of using TIBS in vivo to detect mammographic density as an interim indicator of breast cancer risk. TIBS measurements were completed on 300 women with radiological normal mammograms. White light (625 to 1060 nm) was delivered to the breast tissue and transmitted light was detected on the opposite side of the breast. Principal component analysis was used to reduce the spectral data and generate individual 'risk' scores. Agreement between the obtained 'risk' scores and mammographic density was established using density cluster analysis, the Kappa statistic and logistic regression. The agreement between breast density assessed by mammography and by TIBS was statistically significant for all 'risk' scores. Logistic regression indicated a strong association between the TIBS scores and mammographic density. TIBS provides an alternative to x-ray derived mammographic density as a biomarker of breast density and hence cancer risk.

  14. WHITE STRIPING AND WOODEN BREAST DEFECTS INFLUENCE MEAT QUALITY AND MUSCLE PROTEIN CHARACTERISTICS IN BROILER BREAST MEAT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective was to determine the effects of the wooden breast (WB) and white striping (WS) myopathies on meat quality and protein characteristics of broiler breast meat. Breast fillets (Pectoralis major) from a commercial processing plant were segregated into four groups: normal (neither WS nor W...

  15. Signal enhancement ratio (SER) quantified from breast DCE-MRI and breast cancer risk

    NASA Astrophysics Data System (ADS)

    Wu, Shandong; Kurland, Brenda F.; Berg, Wendie A.; Zuley, Margarita L.; Jankowitz, Rachel C.; Sumkin, Jules; Gur, David

    2015-03-01

    Breast magnetic resonance imaging (MRI) is recommended as an adjunct to mammography for women who are considered at elevated risk of developing breast cancer. As a key component of breast MRI, dynamic contrast-enhanced MRI (DCE-MRI) uses a contrast agent to provide high intensity contrast between breast tissues, making it sensitive to tissue composition and vascularity. Breast DCE-MRI characterizes certain physiologic properties of breast tissue that are potentially related to breast cancer risk. Studies have shown that increased background parenchymal enhancement (BPE), which is the contrast enhancement occurring in normal cancer-unaffected breast tissues in post-contrast sequences, predicts increased breast cancer risk. Signal enhancement ratio (SER) computed from pre-contrast and post-contrast sequences in DCE-MRI measures change in signal intensity due to contrast uptake over time and is a measure of contrast enhancement kinetics. SER quantified in breast tumor has been shown potential as a biomarker for characterizing tumor response to treatments. In this work we investigated the relationship between quantitative measures of SER and breast cancer risk. A pilot retrospective case-control study was performed using a cohort of 102 women, consisting of 51 women who had diagnosed with unilateral breast cancer and 51 matched controls (by age and MRI date) with a unilateral biopsy-proven benign lesion. SER was quantified using fully-automated computerized algorithms and three SER-derived quantitative volume measures were compared between the cancer cases and controls using logistic regression analysis. Our preliminary results showed that SER is associated with breast cancer risk, after adjustment for the Breast Imaging Reporting and Data System (BI-RADS)-based mammographic breast density measures. This pilot study indicated that SER has potential for use as a risk factor for breast cancer risk assessment in women at elevated risk of developing breast cancer.

  16. Breast phantom for mammary tissue characterization by near infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Miranda, D. A.; Cristiano, K. L.; Gutiérrez, J. C.

    2013-11-01

    Breast cancer is a disease associated to a high morbidity and mortality in the entire world. In the study of early detection of breast cancer the development of phantom is so important. In this research we fabricate a breast phantom using a ballistic gel with special modifications to simulate a normal and abnormal human breast. Optical properties of woman breast in the near infrared region were modelled with the phantom we developed. The developed phantom was evaluated with near infrared spectroscopy in order to study its relation with breast tissue. A good optical behaviour was achieved with the model fabricated.

  17. Breast Feeding.

    ERIC Educational Resources Information Center

    International Children's Centre, Paris (France).

    This set of documents consists of English, French, and Spanish translations of four pamphlets on breast-feeding. The pamphlets provide information designed for lay persons, academics and professionals, health personnel and educators, and policy-makers. The contents cover health-related differences between breast and bottle milk; patterns of…

  18. Hierarchical Clustering of Breast Cancer Methylomes Revealed Differentially Methylated and Expressed Breast Cancer Genes

    PubMed Central

    Lin, I-Hsuan; Chen, Dow-Tien; Chang, Yi-Feng; Lee, Yu-Ling; Su, Chia-Hsin; Cheng, Ching; Tsai, Yi-Chien; Ng, Swee-Chuan; Chen, Hsiao-Tan; Lee, Mei-Chen; Chen, Hong-Wei; Suen, Shih-Hui; Chen, Yu-Cheng; Liu, Tze-Tze; Chang, Chuan-Hsiung; Hsu, Ming-Ta

    2015-01-01

    Oncogenic transformation of normal cells often involves epigenetic alterations, including histone modification and DNA methylation. We conducted whole-genome bisulfite sequencing to determine the DNA methylomes of normal breast, fibroadenoma, invasive ductal carcinomas and MCF7. The emergence, disappearance, expansion and contraction of kilobase-sized hypomethylated regions (HMRs) and the hypomethylation of the megabase-sized partially methylated domains (PMDs) are the major forms of methylation changes observed in breast tumor samples. Hierarchical clustering of HMR revealed tumor-specific hypermethylated clusters and differential methylated enhancers specific to normal or breast cancer cell lines. Joint analysis of gene expression and DNA methylation data of normal breast and breast cancer cells identified differentially methylated and expressed genes associated with breast and/or ovarian cancers in cancer-specific HMR clusters. Furthermore, aberrant patterns of X-chromosome inactivation (XCI) was found in breast cancer cell lines as well as breast tumor samples in the TCGA BRCA (breast invasive carcinoma) dataset. They were characterized with differentially hypermethylated XIST promoter, reduced expression of XIST, and over-expression of hypomethylated X-linked genes. High expressions of these genes were significantly associated with lower survival rates in breast cancer patients. Comprehensive analysis of the normal and breast tumor methylomes suggests selective targeting of DNA methylation changes during breast cancer progression. The weak causal relationship between DNA methylation and gene expression observed in this study is evident of more complex role of DNA methylation in the regulation of gene expression in human epigenetics that deserves further investigation. PMID:25706888

  19. Multivariate normality

    NASA Technical Reports Server (NTRS)

    Crutcher, H. L.; Falls, L. W.

    1976-01-01

    Sets of experimentally determined or routinely observed data provide information about the past, present and, hopefully, future sets of similarly produced data. An infinite set of statistical models exists which may be used to describe the data sets. The normal distribution is one model. If it serves at all, it serves well. If a data set, or a transformation of the set, representative of a larger population can be described by the normal distribution, then valid statistical inferences can be drawn. There are several tests which may be applied to a data set to determine whether the univariate normal model adequately describes the set. The chi-square test based on Pearson's work in the late nineteenth and early twentieth centuries is often used. Like all tests, it has some weaknesses which are discussed in elementary texts. Extension of the chi-square test to the multivariate normal model is provided. Tables and graphs permit easier application of the test in the higher dimensions. Several examples, using recorded data, illustrate the procedures. Tests of maximum absolute differences, mean sum of squares of residuals, runs and changes of sign are included in these tests. Dimensions one through five with selected sample sizes 11 to 101 are used to illustrate the statistical tests developed.

  20. Laser ablation of human atherosclerotic plaque without adjacent tissue injury

    NASA Technical Reports Server (NTRS)

    Grundfest, W. S.; Litvack, F.; Forrester, J. S.; Goldenberg, T.; Swan, H. J. C.

    1985-01-01

    Seventy samples of human cadaver atherosclerotic aorta were irradiated in vitro using a 308 nm xenon chloride excimer laser. Energy per pulse, pulse duration and frequency were varied. For comparison, 60 segments were also irradiated with an argon ion and an Nd:YAG laser operated in the continuous mode. Tissue was fixed in formalin, sectioned and examined microscopically. The Nd:YAG and argon ion-irradiated tissue exhibited a central crater with irregular edges and concentric zones of thermal and blast injury. In contrast, the excimer laser-irradiated tissue had narrow deep incisions with minimal or no thermal injury. These preliminary experiments indicate that the excimer laser vaporizes tissue in a manner different from that of the continuous wave Nd:YAG or argon ion laser. The sharp incision margins and minimal damage to adjacent normal tissue suggest that the excimer laser is more desirable for general surgical and intravascular uses than are the conventionally used medical lasers.

  1. Gut Catalase-Positive Bacteria Cross-Protect Adjacent Bifidobacteria from Oxidative Stress.

    PubMed

    Rodríguez, Eva; Peirotén, Ángela; Landete, José María; Medina, Margarita; Arqués, Juan Luis

    2015-01-01

    Bifidobacteria isolated from infant gut and breast milk exhibited different abilities to grow under microaerobic conditions, alone or in the presence of added catalase. In the present study, we demonstrated that some Bifidobacterium strains unable to grow under microaerobic conditions were cross-protected on solid media from oxidative stress by adjacent colonies of gut catalase-positive Staphylococcus epidermidis or Escherichia coli, but not by a catalase-deficient E. coli. The results of this study support the possible contribution of catalase-positive bacteria to the establishment of certain bifidobacteria in non-anaerobic human niches of the infant gastrointestinal tract or mammary gland.

  2. Gut Catalase-Positive Bacteria Cross-Protect Adjacent Bifidobacteria from Oxidative Stress.

    PubMed

    Rodríguez, Eva; Peirotén, Ángela; Landete, José María; Medina, Margarita; Arqués, Juan Luis

    2015-01-01

    Bifidobacteria isolated from infant gut and breast milk exhibited different abilities to grow under microaerobic conditions, alone or in the presence of added catalase. In the present study, we demonstrated that some Bifidobacterium strains unable to grow under microaerobic conditions were cross-protected on solid media from oxidative stress by adjacent colonies of gut catalase-positive Staphylococcus epidermidis or Escherichia coli, but not by a catalase-deficient E. coli. The results of this study support the possible contribution of catalase-positive bacteria to the establishment of certain bifidobacteria in non-anaerobic human niches of the infant gastrointestinal tract or mammary gland. PMID:26040451

  3. Gut Catalase-Positive Bacteria Cross-Protect Adjacent Bifidobacteria from Oxidative Stress

    PubMed Central

    Rodríguez, Eva; Peirotén, Ángela; Landete, José María; Medina, Margarita; Arqués, Juan Luis

    2015-01-01

    Bifidobacteria isolated from infant gut and breast milk exhibited different abilities to grow under microaerobic conditions, alone or in the presence of added catalase. In the present study, we demonstrated that some Bifidobacterium strains unable to grow under microaerobic conditions were cross-protected on solid media from oxidative stress by adjacent colonies of gut catalase-positive Staphylococcus epidermidis or Escherichia coli, but not by a catalase-deficient E. coli. The results of this study support the possible contribution of catalase-positive bacteria to the establishment of certain bifidobacteria in non-anaerobic human niches of the infant gastrointestinal tract or mammary gland. PMID:26040451

  4. Chemotherapy-resistant breast implant-associated anaplastic large cell lymphoma

    PubMed Central

    Parthasarathy, Muralidharan; Orrell, Julian; Mortimer, Caroline; Ball, Liz

    2013-01-01

    A 43-year-old woman presented with a few weeks’ history of discomfort and swelling in her left breast. She had undergone bilateral breast augmentation 8 years previously. There were no risk factors for breast cancer. Clinical examination, mammography and breast ultrasound revealed a large left breast mass adjacent to the breast implant with enlarged axillary lymph nodes. Owing to diagnostic uncertainty, core biopsies were sent to a specialist unit which confirmed breast implant-associated anaplastic large cell lymphoma with involved lymph nodes. Staging investigations confirmed no distant disease. The lymphoma multidisciplinary team recommended cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapy, followed by implant removal and local radiotherapy. However, the patient's disease progressed on first-line, and then second-line chemotherapy. She therefore had a mastectomy and axillary node clearance followed by radiotherapy, with a planned delayed left breast reconstruction and removal of the right breast implant. PMID:24285813

  5. DNA methylation profile of triple negative breast cancer-specific genes comparing lymph node positive patients to lymph node negative patients

    PubMed Central

    Mathe, Andrea; Wong-Brown, Michelle; Locke, Warwick J.; Stirzaker, Clare; Braye, Stephen G.; Forbes, John F.; Clark, Susan J.; Avery-Kiejda, Kelly A.; Scott, Rodney J.

    2016-01-01

    Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with no targeted treatment available. Our previous study identified 38 TNBC-specific genes with altered expression comparing tumour to normal samples. This study aimed to establish whether DNA methylation contributed to these expression changes in the same cohort as well as disease progression from primary breast tumour to lymph node metastasis associated with changes in the epigenome. We obtained DNA from 23 primary TNBC samples, 12 matched lymph node metastases, and 11 matched normal adjacent tissues and assayed for differential methylation profiles using Illumina HumanMethylation450 BeadChips. The results were validated in an independent cohort of 70 primary TNBC samples. The expression of 16/38 TNBC-specific genes was associated with alteration in DNA methylation. Novel methylation changes between primary tumours and lymph node metastases, as well as those associated with survival were identified. Altered methylation of 18 genes associated with lymph node metastasis were identified and validated. This study reveals the important role DNA methylation plays in altered gene expression of TNBC-specific genes and lymph node metastases. The novel insights into progression of TNBC to secondary disease may provide potential prognostic indicators for this hard-to-treat breast cancer subtype. PMID:27671774

  6. [Field matching in breast irradiation

    PubMed

    Varga, Sz; Takácsi Nagy, L; Pesznyák, Cs; Lövey, K; Polgár, I

    2001-01-01

    INTRODUCTION: In this paper the authors have combined different irradiation techniques for breast and adjacent supraclavicular lymph nodes. The aim was to reduce inhomogeneity in the match-line. METHODS: The CadPlan 6.1.5 three-dimensional treatment planning system was applied in this study for CT based plan using a standard medial and lateral wedged tangential breast portals with the adjacent supraclavicular field. Isocenter is placed at depth on the match-line, where asymmetric jaws are used to produce non-divergent field edges. The tangential fields are shaped using multi-leaf collimator (MLC), by following the curvature of the thorax. In this way the cranial vertical match plane is maintaned without using the breast board. The prescribed dose was 50 Gy at the isocentre. RESULTS: The calculated dose distributions were evaluated in three dimension in the match region of supraclavicular field and the two opposing tangential fields. This method produces a more uniform dose distribution in the target volume and in the match-line. Set-up is fast, this is done without the need for table rotation, or vertical cephalad blocks. The average dose to the ipsilateral lung is reduced using the IMRT (intensity modulated radiotherapy) technique by approximately 10% compared with the conventional technique. Furthermore, this new technique has the possibility to improve the field match between the tangential fields and the parasternal field, while maintaning the field match between the tangential fields and the axillary and supraclavicular fields.

  7. CT/FMT dual-model imaging of breast cancer based on peptide-lipid nanoparticles

    NASA Astrophysics Data System (ADS)

    Xu, Guoqiang; Lin, Qiaoya; Lian, Lichao; Qian, Yuan; Lu, Lisen; Zhang, Zhihong

    2016-03-01

    Breast cancer is one of the most harmful cancers in human. Its early diagnosis is expected to improve the patients' survival rate. X-ray computed tomography (CT) has been widely used in tumor detection for obtaining three-dimentional information. Fluorescence Molecular Tomography (FMT) imaging combined with near-infrared fluorescent dyes provides a powerful tool for the acquisition of molecular biodistribution information in deep tissues. Thus, the combination of CT and FMT imaging modalities allows us to better differentiate diseased tissues from normal tissues. Here we developed a tumor-targeting nanoparticle for dual-modality imaging based on a biocompatible HDL-mimicking peptide-phospholipid scaffold (HPPS) nanocarrier. By incorporation of CT contrast agents (iodinated oil) and far-infrared fluorescent dyes (DiR-BOA) into the hydrophobic core of HPPS, we obtained the FMT and CT signals simultaneously. Increased accumulation of the nanoparticles in the tumor lesions was achieved through the effect of the tumor-targeting peptide on the surface of nanoparticle. It resulted in excellent contrast between lesions and normal tissues. Together, the abilities to sensitively separate the lesions from adjacent normal tissues with the aid of a FMT/CT dual-model imaging approach make the targeting nanoparticles a useful tool for the diagnostics of breast cancer.

  8. Breast Cancer Overview

    MedlinePlus

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

  9. Surgery for Breast Cancer

    MedlinePlus

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

  10. Learning about Breast Cancer

    MedlinePlus

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

  11. Fibrocystic breast disease

    MedlinePlus

    Fibrocystic breast disease; Mammary dysplasia; Diffuse cystic mastopathy; Benign breast disease; Glandular breast changes ... FF, Fort GG, et al, eds. Fibrocystic breast disease. In: Ferri FF, ed. Ferri's Clinical Advisor 2015 . ...

  12. Premenstrual breast changes

    MedlinePlus

    Premenstrual tenderness and swelling of the breasts; Breast tenderness - premenstrual; Breast swelling - premenstrual ... Symptoms of premenstrual breast tenderness may range from mild to ... most severe just before each menstrual period Improve during ...

  13. Breast enlargement in males

    MedlinePlus

    Gynecomastia; Breast enlargement in a male ... The condition may occur in one or both breasts. It begins as a small lump beneath the nipple, which may be tender. One breast may be larger than the other. Enlarged breasts ...

  14. Stroma in Breast Development and Disease

    PubMed Central

    Arendt, Lisa M.; Rudnick, Jenny A.; Keller, Patricia J.; Kuperwasser, Charlotte

    2009-01-01

    It is increasingly apparent that normal and malignant breast tissues require complex local and systemic stromal interactions for development and progression. During development, mammary cell fate specification and differentiation require highly regulated contextual signals derived from the stroma. Likewise, during breast carcinoma development, the tissue stroma can provide tumor suppressing and tumor-promoting environments that serve to regulate neoplastic growth of the epithelium. This review focuses on the role of the stroma as a mediator of normal mammary development, as well as a critical regulator of malignant conversion and progression in breast cancer. Recognition of the important role of the stroma during the progression of breast cancers leads to the possibility of new targets for treatment of the initial breast cancer lesion as well as prevention of recurrence. PMID:19857593

  15. Normalizing Rejection.

    PubMed

    Conn, Vicki S; Zerwic, Julie; Jefferson, Urmeka; Anderson, Cindy M; Killion, Cheryl M; Smith, Carol E; Cohen, Marlene Z; Fahrenwald, Nancy L; Herrick, Linda; Topp, Robert; Benefield, Lazelle E; Loya, Julio

    2016-02-01

    Getting turned down for grant funding or having a manuscript rejected is an uncomfortable but not unusual occurrence during the course of a nurse researcher's professional life. Rejection can evoke an emotional response akin to the grieving process that can slow or even undermine productivity. Only by "normalizing" rejection, that is, by accepting it as an integral part of the scientific process, can researchers more quickly overcome negative emotions and instead use rejection to refine and advance their scientific programs. This article provides practical advice for coming to emotional terms with rejection and delineates methods for working constructively to address reviewer comments. PMID:26041785

  16. Hsp90 in the continuum of breast ductal carcinogenesis: Evaluation in precursors, preinvasive and ductal carcinoma lesions

    PubMed Central

    2010-01-01

    Background Hsp90 (heat shock protein90) is a chaperone protein essential for preserving and regulating the function of various cellular proteins. Elevated Hsp90 expression seems to be a trait of breast cancer and may be an integral part of the coping mechanisms that cancer cells exhibit vis-à-vis stress. This manuscript tries to examine the immunohistochemical expression of Hsp90 all along the continuum of breast ductal lesions encompassing ductal hyperplasia without atypia (DHWithoutA), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). Methods Tissue specimens were taken from 30 patients with DHWithoutA, 31 patients with ADH, 51 with DCIS and 51 with IDC. Immunohistochemical assessment of Hsp90 was performed both in the lesion and the adjacent normal breast ducts and lobules; the latter serving as control. Concerning Hsp90 assessment the percentage of positive cells and the intensity were separately analyzed. Subsequently, the Allred score was calculated. Post hoc analysis on the correlations between Hsp90 Allred score and possible predictors (grade, nodal status, tumor size, ER Allred score, PR Allred score, c-erbB-2 status and triple negative status) was conducted in IDC. Results Hsp90 exhibited mainly cytoplasmic immunoreactivity. Hsp90 Allred score exhibited an increasing trend along the continuum of breast ductal lesions (Spearman's rho = 0.169, p = 0.031). Compared to the adjacent normal ducts and lobules, no statistically significant differences were noted in DHwithoutA, ADH and DCIS. Hsp90 expression (intensity, positive cells, Allred score) was higher in IDC, compared to the adjacent normal tissue. Higher Hsp90 expression was observed in grade 2/3 IDCs (borderline association) and tumors of larger size. At the univariable analysis, higher Hsp90 expression was associated with higher ER Allred score, PR Allred score and c-erbB-2 positivity in IDC. Triple-negative IDCs exhibited significantly lower Hsp90

  17. Photodynamic therapy trials with lutetium texaphyrin (Lu-Tex) in patients with locally recurrent breast cancer

    NASA Astrophysics Data System (ADS)

    Renschler, Markus F.; Yuen, Alan R.; Panella, Timothy J.; Wieman, Thomas J.; Dougherty, Shona; Esserman, Laura; Panjehpour, Masoud; Taber, Scott W.; Fingar, Victor H.; Lowe, Elizabeth; Engel, Julie S.; Lum, Bert; Woodburn, Kathryn W.; Cheong, Wai-Fung; Miller, Richard A.

    1998-05-01

    Photodynamic therapy (PDT) of locally recurrent breast cancer has been limited to treatment of small lesions because of non- selective necrosis of adjacent normal tissues in the treatment field. Lutetium Texaphyrin (PCI-0123, Lu-Tex) is a photosensitizer with improved tumor localization that is activated by 732 nm light, which can penetrate through larger tumors. We have evaluated Lu-Tex in a Phase I trial and in an ongoing Phase II trial in women with locally recurrent breast cancer with large tumors who have failed radiation therapy. Patients received Lu-Tex intravenously by rapid infusion 3 hours before illumination of cutaneous or subcutaneous lesions. In Phase I, Lu-Tex doses were escalated from 0.6 to 7.2 mg/kg in 7 cohorts. Sixteen patients with locally recurrent breast cancer lesions were treated. Dose limiting toxicities above 5.5 mg/kg were pain in the treatment field during therapy, and dysesthesias in light exposed areas. No necrosis of normal tissues in the treated field was noticed. Responses were observed in 60% of evaluable patients [n equals 15, 27% complete remission (CR), 33% partial remission (PR)], with 63% of lesions responding (n equals 73: 45% CR, 18% PR). In Phase II, 25 patients have been studied to date, receiving two treatments ranging from 1.0 to 3.0 mg/kg at a 21 day interval. Treatment fields up to 480 cm2 in size were treated successfully and activity has been observed. Patients have experienced pain at the treatment site but no tissue necrosis. These studies demonstrate the feasibility of Lu-Tex PDT to large chest wall areas in women who have failed radiation therapy for the treatment of locally recurrent breast cancer. Treatment conditions are currently being optimized in the ongoing Phase II trials.

  18. Breast ultrasound

    MedlinePlus

    Hacker NF, Friedland ML. Breast disease. In: Hacker NF, Gambone JC, Hobel CJ, eds. Hacker and Moore's Essentials of Obstetrics and Gynecology . 6th ed. Philadelphia, PA: Elsevier; 2016:chap 30. Harvey ...

  19. Breast lift

    MedlinePlus Videos and Cool Tools

    ... are made to accommodate a higher position for the areola and nipple, as well as to remove excess skin and breast tissue. Stitches usually follow the circumference of the areola, the natural lower crease ...

  20. Breast cancer

    MedlinePlus

    ... drink per day (women at high risk for breast cancer should not drink alcohol at all) ... Services Task Force. Risk assessment, genetic counseling, and ... cancer treatment. Bethesda, MD: National Cancer Institute. Date ...

  1. Breast Density and Your Breast Mammogram Report

    MedlinePlus

    Breast Density and Your Mammogram Report Regular mammograms are the best way to find breast cancer early. But if ... But in some women, there’s little change. Breast density is very common, and is not abnormal. How ...

  2. Exchange coupling between laterally adjacent nanomagnets

    NASA Astrophysics Data System (ADS)

    Dey, H.; Csaba, G.; Bernstein, G. H.; Porod, W.

    2016-09-01

    We experimentally demonstrate exchange-coupling between laterally adjacent nanomagnets. Our results show that two neighboring nanomagnets that are each antiferromagnetically exchange-coupled to a common ferromagnetic bottom layer can be brought into strong ferromagnetic interaction. Simulations show that interlayer exchange coupling effectively promotes ferromagnetic alignment between the two nanomagnets, as opposed to antiferromagnetic alignment due to dipole-coupling. In order to experimentally demonstrate the proposed scheme, we fabricated arrays of pairs of elongated, single-domain nanomagnets. Magnetic force microscopy measurements show that most of the pairs are ferromagnetically ordered. The results are in agreement with micromagnetic simulations. The presented scheme can achieve coupling strengths that are significantly stronger than dipole coupling, potentially enabling far-reaching applications in Nanomagnet Logic, spin-wave devices and three-dimensional storage and computing.

  3. Boundary Layers of Air Adjacent to Cylinders

    PubMed Central

    Nobel, Park S.

    1974-01-01

    Using existing heat transfer data, a relatively simple expression was developed for estimating the effective thickness of the boundary layer of air surrounding cylinders. For wind velocities from 10 to 1000 cm/second, the calculated boundary-layer thickness agreed with that determined for water vapor diffusion from a moistened cylindrical surface 2 cm in diameter. It correctly predicted the resistance for water vapor movement across the boundary layers adjacent to the (cylindrical) inflorescence stems of Xanthorrhoea australis R. Br. and Scirpus validus Vahl and the leaves of Allium cepa L. The boundary-layer thickness decreased as the turbulence intensity increased. For a turbulence intensity representative of field conditions (0.5) and for νwindd between 200 and 30,000 cm2/second (where νwind is the mean wind velocity and d is the cylinder diameter), the effective boundary-layer thickness in centimeters was equal to [Formula: see text]. PMID:16658855

  4. 33 CFR 80.1395 - Puget Sound and adjacent waters.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Puget Sound and adjacent waters... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Thirteenth District § 80.1395 Puget Sound and adjacent waters. The 72 COLREGS shall apply on all waters of Puget Sound and adjacent waters, including Lake...

  5. 33 CFR 80.1395 - Puget Sound and adjacent waters.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Puget Sound and adjacent waters... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Thirteenth District § 80.1395 Puget Sound and adjacent waters. The 72 COLREGS shall apply on all waters of Puget Sound and adjacent waters, including Lake...

  6. 33 CFR 80.1395 - Puget Sound and adjacent waters.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Puget Sound and adjacent waters... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Thirteenth District § 80.1395 Puget Sound and adjacent waters. The 72 COLREGS shall apply on all waters of Puget Sound and adjacent waters, including Lake...

  7. 33 CFR 80.1395 - Puget Sound and adjacent waters.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Puget Sound and adjacent waters... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Thirteenth District § 80.1395 Puget Sound and adjacent waters. The 72 COLREGS shall apply on all waters of Puget Sound and adjacent waters, including Lake...

  8. 33 CFR 80.1395 - Puget Sound and adjacent waters.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Puget Sound and adjacent waters... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Thirteenth District § 80.1395 Puget Sound and adjacent waters. The 72 COLREGS shall apply on all waters of Puget Sound and adjacent waters, including Lake...

  9. Normal development.

    PubMed

    Girard, Nadine; Koob, Meriam; Brunel, Herv

    2016-01-01

    Numerous events are involved in brain development, some of which are detected by neuroimaging. Major changes in brain morphology are depicted by brain imaging during the fetal period while changes in brain composition can be demonstrated in both pre- and postnatal periods. Although ultrasonography and computed tomography can show changes in brain morphology, these techniques are insensitive to myelination that is one of the most important events occurring during brain maturation. Magnetic resonance imaging (MRI) is therefore the method of choice to evaluate brain maturation. MRI also gives insight into the microstructure of brain tissue through diffusion-weighted imaging and diffusion tensor imaging. Metabolic changes are also part of brain maturation and are assessed by proton magnetic resonance spectroscopy. Understanding and knowledge of the different steps in brain development are required to be able to detect morphologic and structural changes on neuroimaging. Consequently alterations in normal development can be depicted. PMID:27430460

  10. Lactation following conservation surgery and radiotherapy for breast cancer

    SciTech Connect

    Varsos, G.; Yahalom, J. )

    1991-02-01

    A 38-year-old woman with early stage invasive breast cancer was treated with wide excision of the tumor, axillary lymph node dissection, and breast irradiation. Three years later, she gave birth to a normal baby. She attempted breast feeding and had full lactation from the untreated breast. The irradiated breast underwent only minor changes during pregnancy and postpartum but produced small amounts of colostrum and milk for 2 weeks postpartum. There are only a few reports of lactation after breast irradiation. These cases are reviewed, and possible factors affecting breast function after radiotherapy are discussed. Because of scant information available regarding its safety for the infant, nursing from the irradiated breast is not recommended.

  11. Spectral imaging of breast fibroadenoma using second-harmonic generation

    NASA Astrophysics Data System (ADS)

    Zheng, Liqin; Wang, Yuhua

    2014-09-01

    Fibroadenoma (FA), typically composed of stroma and epithelial cells, is a very common benign breast disease. Women with FA are associated with an increased risk of future breast cancer. The objective of this study was to demonstrate the potential of multiphoton laser scanning microscopy (MPLSM) for characterizing the morphology of collagen in the human breast fibroadenomas. In the study, high-contrast SHG images of human normal breast tissues and fibroadenoma tissues were obtained for comparison. The morphology of collagen was different between normal breast tissue and fibroadenoma. This study shows that MPLSM has the ability to distinguish fibroadenoma tissues from the normal breast tissues based on the noninvasive SHG imaging. With the advent of the clinical portability of miniature MPLSM, we believe that the technique has great potential to be used in vivo studies and for monitoring the treatment responses of fibroadenomas in clinical.

  12. Reference breast temperature: proposal of an equation

    PubMed Central

    de Souza, Gladis Aparecida Galindo Reisemberger; Brioschi, Marcos Leal; Vargas, José Viriato Coelho; Morais, Keli Cristiane Correia; Dalmaso, Carlos; Neves, Eduardo Borba

    2015-01-01

    ABSTRACT Objective To develop an equation to estimate the breast reference temperature according to the variation of room and core body temperatures. Methods Four asymptomatic women were evaluated for three consecutive menstrual cycles. Using thermography, the temperature of breasts and eyes was measured as indirect reference of core body and room temperatures. To analyze the thermal behavior of the breasts during the cycle, the core body and room temperatures were normalized by means of a mathematical equation. Results We performed 180 observations and the core temperature had the highest correlation with the breast temperature, followed by room temperature. The proposed prediction model could explain 45.3% of the breast temperature variation, with variable room temperature variable; it can be accepted as a way to estimate the reference breast temperature at different room temperatures. Conclusion The average breast temperature in healthy women had a direct relation with the core and room temperature and can be estimated mathematically. It is suggested that an equation could be used in clinical practice to estimate the normal breast reference temperature in young women, regardless of the day of the cycle, therefore assisting in evaluation of anatomical studies. PMID:26761549

  13. Normal conus medullaris: CT criteria for recognition

    SciTech Connect

    Grogan, J.P.; Daniels, D.L.; Williams, I.L.; Rauschning, W.; Haughton, V.M.

    1984-06-01

    The normal CT configuration and dimension of the conus medullaris and adjacent spinal cord were determined in 30 patients who had no clinical evidence of conus compression. CT studies were also correlated with anatomic sections in cadavers. The normal conus on CT has a distinctive oval configuration, an arterior sulcus, and a posterior promontory. The anteroposterior diameter ranged from 5 to 8 mm; the transverse diameter from 8 to 11 mm. Intramedullary processes altered both the dimensions and configuration of the conus.

  14. Distinguishing epigenetic features of preneoplastic testis tissues adjacent to seminomas and nonseminomas

    PubMed Central

    Skvortsova, Yulia V.; Zinovyeva, Marina V.; Stukacheva, Elena A.; Klimov, Alexey; Tryakin, Alexey A.; Azhikina, Tatyana L.

    2016-01-01

    PIWI pathway proteins are expressed during spermatogenesis where they play a key role in germ cell development. Epigenetic loss of PIWI proteins expression was previously demonstrated in testicular germ cell tumors (TGCTs), implying their involvement in TGCT development. In this work, apart from studying only normal testis and TGCT samples, we also analyzed an intermediate stage, i.e. preneoplastic testis tissues adjacent to TGCTs. Importantly, in this study, we minimized the contribution of patient-to-patient heterogeneity by using matched preneoplastic/TGCT samples. Surprisingly, expression of germ cell marker DDX4 suggests that spermatogenesis is retained in premalignant testis tissues adjacent to nonseminoma, but not those adjacent to seminoma. Moreover, this pattern is followed by expression of PIWI pathway genes, which impacts one of their functions: DNA methylation level over LINE-1 promoters is higher in preneoplastic testis tissues adjacent to nonseminomas than those adjacent to seminomas. This finding might imply distinct routes for development of the two types of TGCTs and could be used as a novel diagnostic marker, possibly, noninvasively. Finally, we studied the role of CpG island methylation in expression of PIWI genes in patient samples and using in vitro experiments in cell line models: a more complex interrelation between DNA methylation and expression of the corresponding genes was revealed. PMID:26843623

  15. Epigenetic suppression of neprilysin regulates breast cancer invasion

    PubMed Central

    Stephen, H M; Khoury, R J; Majmudar, P R; Blaylock, T; Hawkins, K; Salama, M S; Scott, M D; Cosminsky, B; Utreja, N K; Britt, J; Conway, R E

    2016-01-01

    In women, invasive breast cancer is the second most common cancer and the second cause of cancer-related death. Therefore, identifying novel regulators of breast cancer invasion could lead to additional biomarkers and therapeutic targets. Neprilysin, a cell-surface enzyme that cleaves and inactivates a number of substrates including endothelin-1 (ET1), has been implicated in breast cancer, but whether neprilysin promotes or inhibits breast cancer cell progression and metastasis is unclear. Here, we asked whether neprilysin expression predicts and functionally regulates breast cancer cell invasion. RT–PCR and flow cytometry analysis of MDA-MB-231 and MCF-7 breast cancer cell lines revealed decreased neprilysin expression compared with normal epithelial cells. Expression was also suppressed in invasive ductal carcinoma (IDC) compared with normal tissue. In addition, in vtro invasion assays demonstrated that neprilysin overexpression decreased breast cancer cell invasion, whereas neprilysin suppression augmented invasion. Furthermore, inhibiting neprilysin in MCF-7 breast cancer cells increased ET1 levels significantly, whereas overexpressing neprilysin decreased extracellular-signal related kinase (ERK) activation, indicating that neprilysin negatively regulates ET1-induced activation of mitogen-activated protein kinase (MAPK) signaling. To determine whether neprilysin was epigenetically suppressed in breast cancer, we performed bisulfite conversion analysis of breast cancer cells and clinical tumor samples. We found that the neprilysin promoter was hypermethylated in breast cancer; chemical reversal of methylation in MDA-MB-231 cells reactivated neprilysin expression and inhibited cancer cell invasion. Analysis of cancer databases revealed that neprilysin methylation significantly associates with survival in stage I IDC and estrogen receptor-negative breast cancer subtypes. These results demonstrate that neprilysin negatively regulates the ET axis in breast cancer

  16. Performance assessment of a pendant-geometry CT scanner for breast cancer detection

    NASA Astrophysics Data System (ADS)

    Boone, John M.; Kwan, Alexander L. C.; Nelson, Thomas R.; Shah, Nikula; Burkett, George; Seibert, J. A.; Lindfors, Karen K.; Roos, Gerhardt

    2005-04-01

    While mammography is the gold standard for breast cancer screening worldwide, it is widely recognized that mammography has limitations, especially in women with dense breasts. In response to the need for a more sensitive approach to breast cancer screening, a CT scanner specifically for breast imaging in the pendant geometry was designed, fabricated, and is currently in clinical evaluation. The spatial resolution and noise properties are discussed, and breast images from a normal volunteer and a patient with breast cancer demonstrate very promising breast CT image quality from a qualitative perspective.

  17. Remodeling in myocardium adjacent to an infarction in the pig left ventricle.

    PubMed

    Zimmerman, Scott D; Criscione, John; Covell, James W

    2004-12-01

    Changes in the structure of the "normal" ventricular wall adjacent to an infarcted area involve all components of the myocardium (myocytes, fibroblasts and the extracellular matrix, and the coronary vasculature) and their three-dimensional structural relationship. Assessing changes in these components requires tracking material markers in the remodeling tissue over long periods of time with a three-dimensional approach as well as a detailed histological evaluation of the remodeled structure. The purpose of the present study was to examine the hypotheses that changes in the tissue adjacent to an infarct are related to myocyte elongation, myofiber rearrangement, and changes in the laminar architecture of the adjacent tissue. Three weeks after myocardial infarction, noninfarcted tissue adjacent to the infarct remodeled by expansion along the direction of the fibers and in the cross fiber direction. These changes are consistent with myocyte elongation and myofiber rearrangement (slippage), as well as a change in cell shape to a more elliptical cross section with the major axis in the epicardial tangent plane, and indicate that reorientation of fibers either via "cell slippage" or changes in orientation of the laminar structure of the ventricular wall are quantitatively important aspects of the remodeling of the normally perfused myocardium.

  18. Androgens and breast cancer in men and women.

    PubMed

    Dimitrakakis, Constantine

    2011-09-01

    Abundant clinical evidence suggests that androgens normally inhibit mammary epithelial proliferation and breast growth. Clinical and nonhuman primate studies support the notion that androgens inhibit mammary proliferation and, thus, may protect from breast cancer. On the other hand, administration of conventional estrogen treatment suppresses endogenous androgens and may, thus, enhance estrogenic breast stimulation and possibly breast cancer risk. Addition of testosterone to the usual hormone therapy regimen may diminish the estrogen/progestin increase in breast cancer risk, but the impact of this combined use on mammary gland homeostasis still needs evaluation.

  19. The transareolar incision for breast augmentation revisited.

    PubMed

    Kompatscher, Peter; Schuler, Christine; Beer, Gertrude M

    2004-01-01

    Of the various possible incisions for breast augmentation, the transareolar access has gained only limited popularity. The potential side effects of this incision are said to be altered nipple sensation, impaired lactation, an increased rate of infections with capsular fibrosis, well visible scar formation with hypopigmentation, and the need for an additional access in case a breast ptosis correction should prove necessary at a later date. The purpose of this retrospective study was to judge advantages and limitations of transareolar breast augmentation, and to verify whether the reluctant attitude toward this surgical approach is justified. A sample of 18 patients with a transareolar, retropectoral breast augmentation was selected for a retrospective evaluation. The suitability of the technique in general was examined together with early postoperative complications, sensory changes, and late complications on the basis of an evaluation system for cosmetic surgical results. The study showed that only women with an areolar diameter of 3.5 cm or more without pronounced breast ptosis were suitable for the transareolar access. No early infections were noted. The rate of capsular fibrosis was 11%. Two years after breast augmentation, 16 women (89%) judged their breast sensation to be normal, but objective assessment showed that mean pressure and vibration sensation were moderately compromised in all parts of the breast. The scars were of good quality, with very little hypopigmentation. With appropriate patient selection, respecting the advantages and limitations, the transareolar incision has its definite place among the different incisions for breast augmentation. PMID:15164231

  20. Automated assessment of bilateral breast volume asymmetry as a breast cancer biomarker during mammographic screening

    NASA Astrophysics Data System (ADS)

    Williams, Alex C.; Hitt, Austin; Voisin, Sophie; Tourassi, Georgia

    2013-03-01

    The biological concept of bilateral symmetry as a marker of developmental stability and good health is well established. Although most individuals deviate slightly from perfect symmetry, humans are essentially considered bilaterally symmetrical. Consequently, increased fluctuating asymmetry of paired structures could be an indicator of disease. There are several published studies linking bilateral breast size asymmetry with increased breast cancer risk. These studies were based on radiologists' manual measurements of breast size from mammographic images. We aim to develop a computerized technique to assess fluctuating breast volume asymmetry in screening mammograms and investigate whether it correlates with the presence of breast cancer. Using a large database of screening mammograms with known ground truth we applied automated breast region segmentation and automated breast size measurements in CC and MLO views using three well established methods. All three methods confirmed that indeed patients with breast cancer have statistically significantly higher fluctuating asymmetry of their breast volumes. However, statistically significant difference between patients with cancer and benign lesions was observed only for the MLO views. The study suggests that automated assessment of global bilateral asymmetry could serve as a breast cancer risk biomarker for women undergoing mammographic screening. Such biomarker could be used to alert radiologists or computer-assisted detection (CAD) systems to exercise increased vigilance if higher than normal cancer risk is suspected.

  1. Automated assessment of bilateral breast volume asymmetry as a breast cancer biomarker during mammographic screening

    SciTech Connect

    Williams, Alex C; Hitt, Austin N; Voisin, Sophie; Tourassi, Georgia

    2013-01-01

    The biological concept of bilateral symmetry as a marker of developmental stability and good health is well established. Although most individuals deviate slightly from perfect symmetry, humans are essentially considered bilaterally symmetrical. Consequently, increased fluctuating asymmetry of paired structures could be an indicator of disease. There are several published studies linking bilateral breast size asymmetry with increased breast cancer risk. These studies were based on radiologists manual measurements of breast size from mammographic images. We aim to develop a computerized technique to assess fluctuating breast volume asymmetry in screening mammograms and investigate whether it correlates with the presence of breast cancer. Using a large database of screening mammograms with known ground truth we applied automated breast region segmentation and automated breast size measurements in CC and MLO views using three well established methods. All three methods confirmed that indeed patients with breast cancer have statistically significantly higher fluctuating asymmetry of their breast volumes. However, statistically significant difference between patients with cancer and benign lesions was observed only for the MLO views. The study suggests that automated assessment of global bilateral asymmetry could serve as a breast cancer risk biomarker for women undergoing mammographic screening. Such biomarker could be used to alert radiologists or computer-assisted detection (CAD) systems to exercise increased vigilance if higher than normal cancer risk is suspected.

  2. Breast biopsy - stereotactic

    MedlinePlus

    ... you have breast cancer . Two main types of breast cancer may be found: Ductal carcinoma starts in the tubes (ducts) that move milk from the breast to the nipple. Most breast cancers are of this ... Lobular carcinoma starts in parts of the breast called lobules, ...

  3. Breast biopsy - ultrasound

    MedlinePlus

    ... you have breast cancer. Two main types of breast cancer may be found: Ductal carcinoma starts in the tubes (ducts) that move milk from the breast to the nipple. Most breast cancers are of this ... Lobular carcinoma starts in parts of the breast called lobules, ...

  4. Breast Reconstruction

    MedlinePlus

    If you need a mastectomy, you have a choice about whether or not to have surgery to rebuild the shape of the breast. Instead of ... be done at the same time as the mastectomy, or it may be done later on. If ...

  5. Breast pain

    PubMed Central

    2007-01-01

    Introduction Breast pain may be cyclical (worse before a period) or non-cyclical, originating from the breast or the chest wall, and occurs at some time in 70% of women. Cyclical breast pain resolves spontaneously in 20-30% of women, but tends to recur in 60% of women. Non-cyclical pain responds poorly to treatment but tends to resolve spontaneously in half of women. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for breast pain? We searched: Medline, Embase, The Cochrane Library and other important databases up to January 2006 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 22 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: a low-fat diet, antibiotics, bromocriptine, danazol, diuretics, evening primrose oil, gestrinone, gonadorelin analogues, hormone replacement therapy, lisuride, progestogens, pyridoxine, tamoxifen, tibolone, topical non-steroidal anti-inflammatory drugs, toremifene, and vitamin E. PMID:19454068

  6. Breast pain

    PubMed Central

    2011-01-01

    Introduction Breast pain may be cyclical (worse before a period) or non-cyclical, originating from the breast or the chest wall, and occurs at some time in 70% of women. Cyclical breast pain resolves spontaneously in 20% to 30% of women, but tends to recur in 60% of women. Non-cyclical pain responds poorly to treatment but tends to resolve spontaneously in half of women. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for breast pain? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 24 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, bromocriptine, combined oral contraceptive pill, danazol, diuretics, evening primrose oil, gestrinone, gonadorelin analogues, hormone replacement therapy (HRT), lisuride, low-fat diet, progestogens, pyridoxine, tamoxifen, tibolone, topical or oral non-steroidal anti-inflammatory drugs (NSAIDs), toremifene, and vitamin E. PMID:21477394

  7. Breast pain

    PubMed Central

    2014-01-01

    Introduction Breast pain may be cyclical (worse before a period) or non-cyclical, originating from the breast or the chest wall, and occurs at some time in 70% of women. Cyclical breast pain resolves spontaneously in 20% to 30% of women, but tends to recur in 60% of women. Non-cyclical pain responds poorly to treatment but tends to resolve spontaneously in half of women. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for breast pain? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 11 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: bra wearing, combined oral contraceptive pill, danazol, gonadorelin analogues, progestogens, tamoxifen, and topical or oral non-steroidal anti-inflammatory drugs (NSAIDs).

  8. General Information about Breast Cancer

    MedlinePlus

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

  9. Risks of Breast Cancer Screening

    MedlinePlus

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

  10. Molecular specialization of breast vasculature: A breast-homing phage-displayed peptide binds to aminopeptidase P in breast vasculature

    NASA Astrophysics Data System (ADS)

    Essler, Markus; Ruoslahti, Erkki

    2002-02-01

    In vivo phage display identifies peptides that selectively home to the vasculature of individual organs, tissues, and tumors. Here we report the identification of a cyclic nonapeptide, CPGPEGAGC, which homes to normal breast tissue with a 100-fold selectivity over nontargeted phage. The homing of the phage is inhibited by its cognate synthetic peptide. Phage localization in tissue sections showed that the breast-homing phage binds to the blood vessels in the breast, but not in other tissues. The phage also bound to the vasculature of hyperplastic and malignant lesions in transgenic breast cancer mice. Expression cloning with a phage-displayed cDNA library yielded a phage that specifically bound to the breast-homing peptide. The cDNA insert was homologous to a fragment of aminopeptidase P. The homing peptide bound aminopeptidase P from malignant breast tissue in affinity chromatography. Antibodies against aminopeptidase P inhibited the in vitro binding of the phage-displayed cDNA to the peptide and the in vivo homing of phage carrying the peptide. These results indicate that aminopeptidase P is the receptor for the breast-homing peptide. This peptide may be useful in designing drugs for the prevention and treatment of breast cancer.

  11. miR-146b-5p mediates p16-dependent repression of IL-6 and suppresses paracrine procarcinogenic effects of breast stromal fibroblasts

    PubMed Central

    Al-Ansari, Mysoon M.; Aboussekhra, Abdelilah

    2015-01-01

    Increasing evidence support the critical roles of active stromal fibroblasts in breast cancer development and spread. However, the mediators and the mechanisms of regulation are still not well defined. We have shown here that the tumor suppressor p16INK4A protein inhibits the pro-carcinogenic effects of breast stromal fibroblasts through repressing the expression/secretion of IL-6. Indeed, p16INK4A suppresses IL-6 at the mRNA and protein levels. This effect is mediated trough miR-146b-5p, which inhibits IL-6 expression through a specific sequence at the IL-6 3′UTR. In addition, we present clear evidence that miR-146b-5p inhibition is sufficient to transactivate breast stromal fibroblasts, which promote epithelial-to-mesenchymal-transition in breast cancer cells in a paracrine manner. By contrast, ectopic expression of miR-146b-5p in active fibroblasts abrogated their pro-carcinogenic effects. The physiological importance of miR-146b-5p inhibition was revealed by showing that the levels of pre-miR-146b-5p as well as its mature form are reduced in cancer-associated fibroblasts as compared with their normal adjacent counterparts from cancer-free tissues isolated from the same patients. Interestingly, treatment of active breast stromal fibroblasts with curcumin increased the level of the p16INK4A coding CDKN2A mRNA and miR-146b-5p and suppressed IL-6, which confirms the repressive effect of these two tumor suppressor molecules on IL-6, and shows the possible “normalization” of cancer-related active fibroblasts. These results show that miR-146b-5p has non-cell-autonomous tumor suppressor function through inhibition of IL-6, suggesting that targeting this microRNA in breast stromal fibroblasts could be of great therapeutic value. PMID:26338965

  12. Breast Cancer (For Kids)

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Breast Cancer KidsHealth > For Kids > Breast Cancer Print A A ... for it when they are older. What Is Breast Cancer? The human body is made of tiny building ...

  13. Breast Cancer Disparities

    MedlinePlus

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

  14. Risks of Breast Implants

    MedlinePlus

    ... larger and longer than these conducted so far. Breastfeeding Some women who undergo breast augmentation can successfully ... breast implant silicone shell into breast milk during breastfeeding. Although there are currently no established methods for ...

  15. Male Breast Cancer

    MedlinePlus

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

  16. Breast lump removal

    MedlinePlus

    Lumpectomy; Wide local excision; Breast conservation surgery; Breast-sparing surgery; Partial mastectomy ... If the breast cancer can be seen on imaging tests but the doctor cannot feel it when examining you, a wire ...

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

    PubMed Central

    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

  18. Synchronous luminescence spectroscopy of human breast tissues

    NASA Astrophysics Data System (ADS)

    Majumdar, S. K.; Gupta, P. K.

    1998-06-01

    We report, to our knowledge, the first use of synchronous luminescence (SL) spectroscopy for autofluorescence diagnosis of cancer. The spectral narrowing effect of the SL spectroscopy led to an easier identification of the different fluorophores present in human breast tissues and provided relative estimate of their concentration in qualitative agreement with the estimates obtained from conventional excitation and emission spectroscopy. Further, the SL spectra from human breast tissues could discriminate cancerous tissues from benign tumors and normal tissues with a sensitivity and specificity of 100% in a study involving 34 patients with breast tumor (19 ductal carcinomas and 15 fibroadenomas).

  19. Adhesion between peptides/antibodies and breast cancer cells

    NASA Astrophysics Data System (ADS)

    Meng, J.; Paetzell, E.; Bogorad, A.; Soboyejo, W. O.

    2010-06-01

    Atomic force microscopy (AFM) techniques were used to measure the adhesion forces between the receptors on breast cancer cells specific to human luteinizing hormone-releasing hormone (LHRH) peptides and antibodies specific to the EphA2 receptor. The adhesion forces between LHRH-coated AFM tips and human MDA-MB-231 cells (breast cancer cells) were shown to be about five times greater than those between LHRH-coated AFM tips and normal Hs578Bst breast cells. Similarly, those between EphA2 antibody-coated AFM tips and breast cancer cells were over five times greater than those between EphA2 antibody-coated AFM tips and normal breast cells. The results suggest that AFM can be used for the detection of breast cancer cells in biopsies. The implications of the results are also discussed for the early detection and localized treatment of cancer.

  20. Breast tomography with synchrotron radiation

    NASA Astrophysics Data System (ADS)

    Pani, Silvia; Arfelli, Fulvia; Dreossi, Diego; Montanari, Francesco; Longo, Renata; Olivo, Alessandro; Poropat, Paolo; Zanconati, Fabrizio; Palma, Ludovico D.; Castelli, Edoardo

    2002-05-01

    A feasibility study of breast CT with synchrotron radiation is currently being carried on at Elettra, the Trieste synchrotron radiation facility. Breast CT cannot be implemented easily with conventional radiographic tubes, due to the high dose that would be delivered to the breast by a polychromatic X-ray spectrum. The possibility of tuning the beam energy, available at a synchrotron radiation beamline, allows a significant reduction in the delivered dose, and at the same time the use of monochromatic beams avoids beam hardening artifacts on the reconstructed image. Images of in vitro breast tissue samples have been acquired by means of a high efficiency linear array detector coupled to a VLSI single photon counting readout electronics. The pixel width, determining the pixel size of the reconstructed image, is 200 micrometers , while the pixel height, determining the CT slice thickness, is 300 micrometers . Tomograms have been reconstructed by means of standard filtered backprojection algorithms. Images of normal and pathologic breast tissue samples show a good visibility of glandular structure. The delivered dose was in all cases comparable to the one delivered in clinical planar mammography. Due to the promising results we obtained, in vivo studies are under evaluation.

  1. High SPARC Expression Starting from Dysplasia, Associated with Breast Carcinoma, Is Predictive for Bone Metastasis without Enhancement of Plasma Levels

    PubMed Central

    Maroni, Paola; Bendinelli, Paola; Morelli, Daniele; Drago, Lorenzo; Luzzati, Alessandro; Perrucchini, Giuseppe; Bonini, Chiara; Matteucci, Emanuela; Desiderio, Maria Alfonsina

    2015-01-01

    In order to become established in the skeleton, metastatic cells disseminating from the breast carcinoma need to acquire organ-specific traits. There are no effective predictors for who will develop bone metastasis to guide long-term predictive therapy. Our purpose was to individuate events critical for bone colonization to make a molecular classification of breast carcinoma useful for bone-metastasis outcome. In dysplasia adjacent to carcinoma and in pair-matched specimens of bone metastasis we examined SPARC expression and localization as well as Endothelin 1/ETAR signals by immunohistochemistry, and the evaluation of plasma levels of SPARC by ELISA was also performed. In patients with breast carcinoma metastasizing to bone, SPARC and Endothelin 1/ETAR axis were highly expressed from dysplasia until bone metastasis, but the SPARC plasma level was as low as that of normal women, in contrast to patients that never develop bone metastasis, suggesting that circulating SPARC was counter adhesive. Altogether, the early identification of SPARC/Endothelin 1/ETAR in dysplastic lesions would be important to devise therapies preventing metastasis engraftment, since often carcinoma cells spread to distant organs at the time or even before patients present with cancer. PMID:26703564

  2. High SPARC Expression Starting from Dysplasia, Associated with Breast Carcinoma, Is Predictive for Bone Metastasis without Enhancement of Plasma Levels.

    PubMed

    Maroni, Paola; Bendinelli, Paola; Morelli, Daniele; Drago, Lorenzo; Luzzati, Alessandro; Perrucchini, Giuseppe; Bonini, Chiara; Matteucci, Emanuela; Desiderio, Maria Alfonsina

    2015-01-01

    In order to become established in the skeleton, metastatic cells disseminating from the breast carcinoma need to acquire organ-specific traits. There are no effective predictors for who will develop bone metastasis to guide long-term predictive therapy. Our purpose was to individuate events critical for bone colonization to make a molecular classification of breast carcinoma useful for bone-metastasis outcome. In dysplasia adjacent to carcinoma and in pair-matched specimens of bone metastasis we examined SPARC expression and localization as well as Endothelin 1/ETAR signals by immunohistochemistry, and the evaluation of plasma levels of SPARC by ELISA was also performed. In patients with breast carcinoma metastasizing to bone, SPARC and Endothelin 1/ETAR axis were highly expressed from dysplasia until bone metastasis, but the SPARC plasma level was as low as that of normal women, in contrast to patients that never develop bone metastasis, suggesting that circulating SPARC was counter adhesive. Altogether, the early identification of SPARC/Endothelin 1/ETAR in dysplastic lesions would be important to devise therapies preventing metastasis engraftment, since often carcinoma cells spread to distant organs at the time or even before patients present with cancer. PMID:26703564

  3. High SPARC Expression Starting from Dysplasia, Associated with Breast Carcinoma, Is Predictive for Bone Metastasis without Enhancement of Plasma Levels.

    PubMed

    Maroni, Paola; Bendinelli, Paola; Morelli, Daniele; Drago, Lorenzo; Luzzati, Alessandro; Perrucchini, Giuseppe; Bonini, Chiara; Matteucci, Emanuela; Desiderio, Maria Alfonsina

    2015-11-26

    In order to become established in the skeleton, metastatic cells disseminating from the breast carcinoma need to acquire organ-specific traits. There are no effective predictors for who will develop bone metastasis to guide long-term predictive therapy. Our purpose was to individuate events critical for bone colonization to make a molecular classification of breast carcinoma useful for bone-metastasis outcome. In dysplasia adjacent to carcinoma and in pair-matched specimens of bone metastasis we examined SPARC expression and localization as well as Endothelin 1/ETAR signals by immunohistochemistry, and the evaluation of plasma levels of SPARC by ELISA was also performed. In patients with breast carcinoma metastasizing to bone, SPARC and Endothelin 1/ETAR axis were highly expressed from dysplasia until bone metastasis, but the SPARC plasma level was as low as that of normal women, in contrast to patients that never develop bone metastasis, suggesting that circulating SPARC was counter adhesive. Altogether, the early identification of SPARC/Endothelin 1/ETAR in dysplastic lesions would be important to devise therapies preventing metastasis engraftment, since often carcinoma cells spread to distant organs at the time or even before patients present with cancer.

  4. Optical imaging for breast cancer prescreening

    PubMed Central

    Godavarty, Anuradha; Rodriguez, Suset; Jung, Young-Jin; Gonzalez, Stephanie

    2015-01-01

    Breast cancer prescreening is carried out prior to the gold standard screening using X-ray mammography and/or ultrasound. Prescreening is typically carried out using clinical breast examination (CBE) or self-breast examinations (SBEs). Since CBE and SBE have high false-positive rates, there is a need for a low-cost, noninvasive, non-radiative, and portable imaging modality that can be used as a prescreening tool to complement CBE/SBE. This review focuses on the various hand-held optical imaging devices that have been developed and applied toward early-stage breast cancer detection or as a prescreening tool via phantom, in vivo, and breast cancer imaging studies. Apart from the various optical devices developed by different research groups, a wide-field fiber-free near-infrared optical scanner has been developed for transillumination-based breast imaging in our Optical Imaging Laboratory. Preliminary in vivo studies on normal breast tissues, with absorption-contrasted targets placed in the intramammary fold, detected targets as deep as 8.8 cm. Future work involves in vivo imaging studies on breast cancer subjects and comparison with the gold standard X-ray mammography approach. PMID:26229503

  5. Ius Chasma Tributary Valleys and Adjacent Plains

    NASA Technical Reports Server (NTRS)

    2006-01-01

    This image covers valley tributaries of Ius Chasma, as well as the plains adjacent to the valleys. Ius Chasma is one of several canyons that make up the Valles Marineris canyon system. Valles Marineris likely formed by extension associated with the growth of the large volcanoes and topographic high of Tharsis to the northwest. As the ground was pulled apart, large and deep gaps resulted in the valleys seen in the top and bottom of this HiRISE image. Ice that was once in the ground could have also melted to create additional removal of material in the formation of the valleys. HiRISE is able to see the rocks along the walls of both these valleys and also impact craters in the image. Rock layers that appear lower down in elevation appear rougher and are shedding boulders. Near the top of the walls and also seen in patches along the smooth plains are brighter layers. These brighter layers are not shedding boulders so they must represent a different kind of rock formed in a different kind of environment than those further down the walls. Because they are highest in elevation, the bright layers are youngest in age. HiRISE is able to see dozens of the bright layers, which are perhaps only a meter in thickness. Darker sand dunes and ripples cover most of the plains and fill the floors of impact craters.

    Image PSP_001351_1715 was taken by the High Resolution Imaging Science Experiment (HiRISE) camera onboard the Mars Reconnaissance Orbiter spacecraft on November 9, 2006. The complete image is centered at -8.3 degrees latitude, 275.4 degrees East longitude. The range to the target site was 254.3 km (158.9 miles). At this distance the image scale ranges from 25.4 cm/pixel (with 1 x 1 binning) to 101.8 cm/pixel (with 4 x 4 binning). The image shown here has been map-projected to 25 cm/pixel and north is up. The image was taken at a local Mars time of 3:32 PM and the scene is illuminated from the west with a solar incidence angle of 59 degrees, thus the sun was about

  6. Diagnostic and prognostic value of serum nitric oxide, tumor necrosis factor-alpha, basic fibroblast growth factor and copper as angiogenic markers in premenopausal breast cancer patients: a case-control study.

    PubMed

    Hewala, T I; Abd El-Moneim, N A; Ebied, S Abd El-Moneim; Sheta, M I; Soliman, K; Abu-Elenean, A

    2010-01-01

    Many studies demonstrate that increased microvessel density (MVD) surrounding primary tumour is associated with decreased overall survival in patients with breast cancer. This study compares the diagnostic and prognostic values of the angiogenic serum factors nitric oxide (NO), tumour necrosis factor-alpha (TNFalpha), basic fibroblast growth factor (bFGF) and copper with those of serum CA15-3 as the standard tumour marker in breast cancer patients. Microvessel density was estimated in CD31-immunostained sections from breast cancer patients. Before surgery, NO, TNFalpha, bFGF, copper and CA 15-3 were measured in serum samples from 30 premenopausal breast cancer patients in comparison with 15 healthy controls. The diagnostic values of the assayed parameters were compared using receiver operating characteristic (ROC) curve analysis. Univariate survival analysis of patients was assessed using the Kaplan-Meier method. Breast cancer tissues showed higher MVD than did normal breast tissues adjacent to the tumour (P = 0.008). Before surgery, tumour MVD correlated significantly with serum NO, TNFalpha, bFGF and copper (r = 0.458, P = .011; r = 0.379, P = .039; r = 0.513, P = .004 and r = 0.613, P = 0.000, respectively). Serum NO, TNFalpha, bFGF, copper and CA 15-3 levels in patients were significantly elevated compared with controls (P = 0.011, P = 0.004, P = 0.039, P = 0.000 and P = 0.001, respectively). Kaplan-Meier analysis revealed that patients with elevated serum TNFalpha, CA 15-3 and copper (P = 0.035, P = 0.040, P = 0.0339, respectively) had an overall survival significantly shorter than those who had lower levels of these parameters. These data suggest that serum TNFalpha, CA 15-3 and copper are useful predictive markers for overall survival in premenopausal breast cancer patients.

  7. A novel double-negative feedback loop between miR-489 and the HER2-SHP2-MAPK signaling axis regulates breast cancer cell proliferation and tumor growth

    PubMed Central

    Lee, Ji Shin; Markoutsa, Eleni; Jie, Chunfa; Liu, Shou; Botbyl, Rachel; Reisman, David; Xu, Peisheng; Chen, Hexin

    2016-01-01

    Human epidermal growth factor receptor 2 (HER2 or ErBb2) is a receptor tyrosine kinase overexpressed in 20-30% of breast cancers and associated with poor prognosis and outcome. Dysregulation of several microRNAs (miRNAs) plays a key role in breast cancer progression and metastasis. In this study, we screened and identified miRNAs dysregualted in HER2-positive breast cancer cells. Our molecular study demonstrated that miR-489 was specifically downregulated by the HER2-downstream signaling, especially through the MAPK pathway. Restoration or overexpression of miR-489 in HER2-positive breast cancer cells significantly inhibited cell growth in vitro and decreased the tumorigenecity and tumor growth in xenograft mice. Mechanistically, we found that overexpression of miR-489 led to the decreased levels of HER2 and SHP2 and thus attenuated HER2-downstream signaling. Furthermore, we for the first time demonstrated that HER2 is a direct target of miR-489 and therefore HER2-SHP2-MAPK and miR-489 signaling pathways form a mutually inhibitory loop. Using quantitative real-time PCR analysis and Fluorescent in situ hybridization technique (FISH), we found that miR-489 was expressed at significantly lower level in tumor tissues compared to the adjacent normal tissues. Downregulation of miR-489 in breast cancers was associated with aggressive tumor phenotypes. Overall, our results define a double-negative feedback loop involving miR-489 and the HER2-SHP2-MAPK signaling axis that can regulate breast cancer cell proliferation and tumor progression and might have therapeutic relevance for HER2-positive breast cancer. PMID:26918448

  8. Learning Non-Adjacent Regularities at Age 0 ; 7

    ERIC Educational Resources Information Center

    Gervain, Judit; Werker, Janet F.

    2013-01-01

    One important mechanism suggested to underlie the acquisition of grammar is rule learning. Indeed, infants aged 0 ; 7 are able to learn rules based on simple identity relations (adjacent repetitions, ABB: "wo fe fe" and non-adjacent repetitions, ABA: "wo fe wo", respectively; Marcus et al., 1999). One unexplored issue is…

  9. View of north side from exterior stairs of adjacent building, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View of north side from exterior stairs of adjacent building, bottom cut off by fringed buildings, view facing south-southwest - U.S. Naval Base, Pearl Harbor, Industrial X-Ray Building, Off Sixth Street, adjacent to and south of Facility No. 11, Pearl City, Honolulu County, HI

  10. Delayed Acquisition of Non-Adjacent Vocalic Distributional Regularities

    ERIC Educational Resources Information Center

    Gonzalez-Gomez, Nayeli; Nazzi, Thierry

    2016-01-01

    The ability to compute non-adjacent regularities is key in the acquisition of a new language. In the domain of phonology/phonotactics, sensitivity to non-adjacent regularities between consonants has been found to appear between 7 and 10 months. The present study focuses on the emergence of a posterior-anterior (PA) bias, a regularity involving two…

  11. A novel technique for teaching challenging ultrasound-guided breast procedures to radiology residents.

    PubMed

    Sutcliffe, Joseph; Hardman, Rulon L; Dornbluth, Nella Carol; Kist, Ken A

    2013-10-01

    Ultrasound-guided breast interventions (core biopsies, needle-wire localizations, and fine-needle cyst aspirations) are common procedures performed by radiologists. Residents must gain competency in these interventions during training. Phantoms and simulations have been advocated for teaching interventions, and various systems are available for standard breast interventions. However, simulations for difficult/high-risk interventions are not readily available. We describe an inexpensive method for simulating difficult ultrasound-guided breast procedures, including masses over breast implants, deep masses along the chest wall, and lymph nodes adjacent to axillary vessels.

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

    PubMed

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

    2015-12-01

    The normal physiologic stress mechanism, mediated by the sympathetic nervous system, causes a release of the neurotransmitters epinephrine and norepinephrine. Preclinical data have demonstrated an effect on tumor progression and metastasis via the sympathetic nervous system mediated primarily through the β-adrenergic receptor (β-AR) pathway. In vitro data have shown an increase in tumor growth, migration, tumor angiogenesis, and metastatic spread in breast cancer through activation of the β-AR. Retrospective cohort studies on the clinical outcomes of β-blockers in breast cancer outcomes showed no clear consensus. The purpose of this study was to perform a systematic review and meta-analysis of the effect of β-blockers on breast cancer outcomes. A systematic review was performed using the Cochrane library and PubMed. Publications between the dates of January 2010 and December 2013 were identified. Available hazard ratios (HRs) were extracted for breast cancer recurrence, breast cancer death, and all-cause mortality and pooled using a random effects meta-analysis. A total of 7 studies contained results for at least 1 of the outcomes of breast cancer recurrence, breast cancer death, or all-cause mortality in breast cancer patients receiving β-blockers. In the 5 studies that contained results for breast cancer recurrence, there was no statistically significant risk reduction (HR, 0.67; 95% confidence interval [CI], 0.39-1.13). Breast cancer death results were contained in 4 studies, which also suggested a significant reduction in risk (HR, 0.50; 95% CI, 0.32-0.80). Among the 4 studies that reported all-cause mortality, there was no significant effect of β-blockers on risk (HR, 1.02; 95% CI, 0.75-1.37). Results of this systematic review and meta-analysis suggest that the use of β-blockers significantly reduced risk of breast cancer death among women with breast cancer. PMID:26516037

  13. Breast Pain: Clinical Pattern and Aetiology in a Breast Clinic in Eastern Nigeria

    PubMed Central

    Egwuonwu, Ochonma A; Anyanwu, Stanley NC; Chianakwana, Gabriel U; Ihekwoaba, Eric C

    2016-01-01

    Background: Patients with breast pain are likely to be very worried because some consider pain in the breast as an indication of malignancy. Objective: To highlight the causes of pain in the patients are presenting to our breast clinic. Materials and Methods: A prospective study of all consenting patients with breast disease presenting to the breast clinic was conducted from January 2004 to December 2008. Results: A total of 664 patients presented to the breast clinic during the study period. Of this number, 127 presented with breast pain either as the sole symptom or in association with other symptoms. The presenting complaints were a pain, pain with lump, and pain with nipple discharge in 63 (49.6%), 59 (46.4%), and 5 (4.0%) patients, respectively. The pain was noncyclical in 96 (75.6%) patients. The site of the pain was whole breast in 87 (68.5%) patients and a lump in 40 (31.5%). The clinical diagnosis in 31 (24.4%) cases was fibrocystic disease, 28 (22.0%) cancer, 23 (18.1%) unknown, 10 (7.9%) fibroadenoma, 8 (6.3%) duct ectasia, 6 (4.7%) normal breast, and others 21 (16.5%) cases benign diseases were diagnosed. The histological diagnosis was fibrocystic changes, carcinoma, and fibroadenoma in 15 (42.9%), 10 (28.6%), and 5 (14.3%) patients, respectively. Others were benign phyllodes, abscess, duct ectasia, chronic mastitis, and lipoma, each constituting 1 (2.9%) case. Conclusion: Breast pain constitutes a small proportion of complaints to our breast clinic. Fibrocystic changes were the most common cause of breast pain both clinically and histologically. PMID:27013851

  14. A Rodent Model to Evaluate the Tissue Response to a Biological Scaffold When Adjacent to a Synthetic Material.

    PubMed

    Dearth, Christopher L; Keane, Timothy J; Scott, Jeffrey R; Daly, Kerry A; Badylak, Stephen F

    2015-10-01

    The use of biologic scaffold materials adjacent to synthetic meshes is commonplace. A prevalent clinical example is two-staged breast reconstruction, where biologic scaffolds are used to provide support and coverage for the inferior aspect of the synthetic expander. However, limited data exist regarding either the kinetics of biologic scaffold integration or the host tissue response to the biologic scaffold materials used for this application or other applications in which such scaffold materials are used. The present study evaluated the temporal host response to a biological scaffold when placed adjacent to a synthetic material. Evaluation criteria included quantification of material contracture and characterization of the host cell response and tissue remodeling events. Results show a decreased thickness of the collagenous tissue layer at biologic scaffold/silicone interface compared to the abdominal wall/silicone interface during the 12-week experimental time course. All test materials were readily incorporated into surrounding host tissue. PMID:26176992

  15. [Treatment of disseminated breast cancer].

    PubMed

    Mattson, Johanna; Huovinen, Riikka

    2015-01-01

    Although several effective drugs have in recent years been introduced for the treatment of disseminated breast cancer, it is still an incurable illness. Many patients live a fairly normal life with their illness for a long time, and some of them are able to continue working in spite of the therapies. Factors considered in tailoring the treatment include tumor subtype, extent of the disease, symptoms, previous treatments and the achieved treatment outcome, and adverse effects of the treatments. PMID:26245064

  16. Cytomegalovirus and Epstein-Barr Virus in Breast Cancer

    PubMed Central

    Richardson, Ann K.; Currie, Margaret J.; Robinson, Bridget A.; Morrin, Helen; Phung, Yen; Pearson, John F.; Anderson, Trevor P.; Potter, John D.; Walker, Logan C.

    2015-01-01

    Findings of polymerase chain reaction (PCR) studies of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) and breast cancer vary, making it difficult to determine whether either, both, or neither virus is causally associated with breast cancer. We investigated CMV and EBV in paired samples of breast cancer and normal breast tissue from 70 women using quantitative PCR. A serum sample from each woman was tested for CMV and EBV IgG. To place our results in context, we reviewed the existing literature and performed a meta-analysis of our results together with previous PCR studies of EBV, CMV, and breast cancer. Of the serology samples, 67 of 70 (96%) were EBV IgG positive and 49 of 70 (70%) were CMV IgG positive. QPCR detected EBV in 24 (34%) of the tumour and 9 (13%) of the paired normal specimens and CMV in 0 (0%) of the tumour and 2 (3%) of the paired normal specimens. Our findings, together with earlier results summarised in the meta-analysis, suggest several possibilities: variable findings may be due to limitations of molecular analyses; ‘hit and run’ oncogenesis may lead to inconsistent results; one or both viruses has a role at a later stage in breast cancer development; infection with multiple viruses increases breast cancer risk; or neither virus has a role. Future studies should focus on ways to investigate these possibilities, and should include comparisons of breast cancer tissue samples with appropriate normal tissue samples. PMID:25723522

  17. Mammary Development and Breast Cancer: A Wnt Perspective

    PubMed Central

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

    2016-01-01

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

  18. Mammary Development and Breast Cancer: A Wnt Perspective.

    PubMed

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

    2016-01-01

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

  19. Breast Cancer -- Male

    MedlinePlus

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

  20. Breast cancer in men

    MedlinePlus

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

  1. Living Beyond Breast Cancer

    MedlinePlus

    ... Instagram YouTube 2,600 men are diagnosed with breast cancer each year. Learn about risk factors, treatment options ... help hundreds of thousands of people affected by breast cancer. Donate Today Breast Cancer inFocus: Breast Cancer During ...

  2. Aberrant gene expression in mucosa adjacent to tumor reveals a molecular crosstalk in colon cancer

    PubMed Central

    2014-01-01

    Background A colorectal tumor is not an isolated entity growing in a restricted location of the body. The patient’s gut environment constitutes the framework where the tumor evolves and this relationship promotes and includes a complex and tight correlation of the tumor with inflammation, blood vessels formation, nutrition, and gut microbiome composition. The tumor influence in the environment could both promote an anti-tumor or a pro-tumor response. Methods A set of 98 paired adjacent mucosa and tumor tissues from colorectal cancer (CRC) patients and 50 colon mucosa from healthy donors (246 samples in total) were included in this work. RNA extracted from each sample was hybridized in Affymetrix chips Human Genome U219. Functional relationships between genes were inferred by means of systems biology using both transcriptional regulation networks (ARACNe algorithm) and protein-protein interaction networks (BIANA software). Results Here we report a transcriptomic analysis revealing a number of genes activated in adjacent mucosa from CRC patients, not activated in mucosa from healthy donors. A functional analysis of these genes suggested that this active reaction of the adjacent mucosa was related to the presence of the tumor. Transcriptional and protein-interaction networks were used to further elucidate this response of normal gut in front of the tumor, revealing a crosstalk between proteins secreted by the tumor and receptors activated in the adjacent colon tissue; and vice versa. Remarkably, Slit family of proteins activated ROBO receptors in tumor whereas tumor-secreted proteins transduced a cellular signal finally activating AP-1 in adjacent tissue. Conclusions The systems-level approach provides new insights into the micro-ecology of colorectal tumorogenesis. Disrupting this intricate molecular network of cell-cell communication and pro-inflammatory microenvironment could be a therapeutic target in CRC patients. PMID:24597571

  3. Calcium-Sensing Receptor in Breast Physiology and Cancer

    PubMed Central

    Kim, Wonnam; Wysolmerski, John J.

    2016-01-01

    The calcium-sensing receptor (CaSR) is expressed in normal breast epithelial cells and in breast cancer cells. During lactation, activation of the CaSR in mammary epithelial cells increases calcium transport into milk and inhibits parathyroid hormone-related protein (PTHrP) secretion into milk and into the circulation. The ability to sense changes in extracellular calcium allows the lactating breast to actively participate in the regulation of systemic calcium and bone metabolism, and to coordinate calcium usage with calcium availability during milk production. Interestingly, as compared to normal breast cells, in breast cancer cells, the regulation of PTHrP secretion by the CaSR becomes rewired due to a switch in its G-protein usage such that activation of the CaSR increases instead of decreases PTHrP production. In normal cells the CaSR couples to Gαi to inhibit cAMP and PTHrP production, whereas in breast cancer cells, it couples to Gαs to stimulate cAMP and PTHrP production. Activation of the CaSR on breast cancer cells regulates breast cancer cell proliferation, death and migration, in part, by stimulating PTHrP production. In this article, we discuss the biology of the CaSR in the normal breast and in breast cancer, and review recent findings suggesting that the CaSR activates a nuclear pathway of PTHrP action that stimulates cellular proliferation and inhibits cell death, helping cancer cells adapt to elevated extracellular calcium levels. Understanding the diverse actions mediated by the CaSR may help us better understand lactation physiology, breast cancer progression and osteolytic bone metastases. PMID:27746743

  4. Millimeter Wave Spectroscopy for Breast Cancer Diagnostics and Detection

    NASA Astrophysics Data System (ADS)

    Korolev, Konstantin; Chen, Shu; Afsar, Mohammed; Naber, Stephen

    2009-03-01

    Broad-band millimeter wave transmittance measurements of normal and tumorous (cancerous) human breast tissue samples have been acquired in--vitro by employing a free-space, quasi-optical spectrometer. Freshly excised breast tissues were prepared and preserved in 10% neutral-buffered formalin solution before testing. Significant differences in the transmittance profiles have been found between the normal and tumorous tissues. It has been found that despite the inhomogeneity and variable structure and composition of each single tissue, the tumorous specimens consistently manifest much higher absorption level of millimeter wave radiation than the normal ones. It has been shown that free space, quasi-optical spectrometer is capable of contributing valuable insights into the dielectric properties of normal and tumorous human breast tissues and aiding in further developments of millimeter wave spectroscopy and mammography for the breast cancer diagnostics and detection.

  5. The evolution of accelerated, partial breast irradiation as a potential treatment option for women with newly diagnosed breast cancer considering breast conservation.

    PubMed

    Dirbas, Frederick M; Jeffrey, Stefanie S; Goffinet, Don R

    2004-12-01

    Breast conservation therapy (BCT) is a safe, effective alternative to mastectomy for many women with newly diagnosed breast cancer. This approach involves local excision of the malignancy with tumor-free margins, followed by 5-7 weeks of external beam whole breast (WB) radiotherapy (XRT) to minimize the risk of an in-breast tumor recurrence (IBTR). Though clearly beneficial, the extended course of almost daily postoperative radiotherapy interrupts normal activities and lengthens care. Additional options are now available that shorten the radiotherapy treatment time to 1-5 days (accelerated) and focus an increased dose of radiation on just the breast tissue around the excision cavity (partial breast). Recent trials with accelerated, partial breast irradiation (APBI) have shown promise as a potential replacement to the longer, whole breast treatments for select women with early-stage breast cancer. Current APBI approaches include interstitial brachytherapy, intracavitary (balloon) brachytherapy, and accelerated external beam (3-D conformal) radiotherapy, all of which normally complete treatment over 5 days, while intraoperative radiotherapy (IORT) condenses the entire treatment into a single dose delivered immediately after tumor excision. Each approach has benefits and limitations. This study covers over 2 decades of clinical trials exploring APBI, discusses treatment variables that appear necessary for successful implementation of this new form of radiotherapy, compares and contrasts the various APBI approaches, and summarizes current and planned randomized trials that will shape if and how APBI is introduced into routine clinical care. Some of the more important outcome variables from these trials will be local toxicity, local and regional recurrence, and overall survival. If APBI options are ultimately demonstrated to be as safe and effective as current whole breast radiotherapy approaches, breast conservation may become an even more appealing choice, and the

  6. Optically measured microvascular blood flow contrast of malignant breast tumors.

    PubMed

    Choe, Regine; Putt, Mary E; Carlile, Peter M; Durduran, Turgut; Giammarco, Joseph M; Busch, David R; Jung, Ki Won; Czerniecki, Brian J; Tchou, Julia; Feldman, Michael D; Mies, Carolyn; Rosen, Mark A; Schnall, Mitchell D; DeMichele, Angela; Yodh, Arjun G

    2014-01-01

    Microvascular blood flow contrast is an important hemodynamic and metabolic parameter with potential to enhance in vivo breast cancer detection and therapy monitoring. Here we report on non-invasive line-scan measurements of malignant breast tumors with a hand-held optical probe in the remission geometry. The probe employs diffuse correlation spectroscopy (DCS), a near-infrared optical method that quantifies deep tissue microvascular blood flow. Tumor-to-normal perfusion ratios are derived from thirty-two human subjects. Mean (95% confidence interval) tumor-to-normal ratio using surrounding normal tissue was 2.25 (1.92-2.63); tumor-to-normal ratio using normal tissues at the corresponding tumor location in the contralateral breast was 2.27 (1.94-2.66), and using normal tissue in the contralateral breast was 2.27 (1.90-2.70). Thus, the mean tumor-to-normal ratios were significantly different from unity irrespective of the normal tissue chosen, implying that tumors have significantly higher blood flow than normal tissues. Therefore, the study demonstrates existence of breast cancer contrast in blood flow measured by DCS. The new, optically accessible cancer contrast holds potential for cancer detection and therapy monitoring applications, and it is likely to be especially useful when combined with diffuse optical spectroscopy/tomography. PMID:24967878

  7. Enhancement of radiotherapy by ceria nanoparticles modified with neogambogic acid in breast cancer cells

    PubMed Central

    Chen, Feng; Zhang, Xiao Hong; Hu, Xiao Dan; Zhang, Wei; Lou, Zhi Chao; Xie, Li Hua; Liu, Pei Dang; Zhang, Hai Qian

    2015-01-01

    Radiotherapy is one of the main strategies for cancer treatment but has significant challenges, such as cancer cell resistance and radiation damage to normal tissue. Radiosensitizers that selectively increase the susceptibility of cancer cells to radiation can enhance the effectiveness of radiotherapy. We report here the development of a novel radiosensitizer consisting of monodispersed ceria nanoparticles (CNPs) covered with the anticancer drug neogambogic acid (NGA-CNPs). These were used in conjunction with radiation in MCF-7 breast cancer cells, and the efficacy and mechanisms of action of this combined treatment approach were evaluated. NGA-CNPs potentiated the toxic effects of radiation, leading to a higher rate of cell death than either treatment used alone and inducing the activation of autophagy and cell cycle arrest at the G2/M phase, while pretreatment with NGA or CNPs did not improve the rate of radiation-induced cancer cells death. However, NGA-CNPs decreased both endogenous and radiation-induced reactive oxygen species formation, unlike other nanomaterials. These results suggest that the adjunctive use of NGA-CNPs can increase the effectiveness of radiotherapy in breast cancer treatment by lowering the radiation doses required to kill cancer cells and thereby minimizing collateral damage to healthy adjacent tissue. PMID:26316742

  8. View point: How to make women familiar with their breasts?

    PubMed

    Khokhar, Anita

    2013-01-01

    There is a consensus among researchers about the fact that women should be familiar with their breasts but there is a lot of argument as to how to make them aware of what is normal for them. For over decades breast self examination (BSE) was advocated for the same but as an outcome of work conducted by researchers in various countires a controversy has been raised in the West. In a country like India, where breast cancer screening is not popular and limited resources are available we should question what would be the best strategy to make women familiar with their breasts to facilitate best use of BSE.

  9. The adolescent female: Breast and reproductive embryology and anatomy.

    PubMed

    Lemaine, Valerie; Simmons, Patricia S

    2013-01-01

    Congenital breast and genital tract anomalies are seen frequently in the care of children and adolescents. Breast and internal gynecologic anomalies more often present in adolescence than in early childhood. Management is best delivered through a multidisciplinary team approach. Carefully timed surgical intervention is of importance to optimize psychological, aesthetic and functional outcomes. An understanding of the female breast and genital tract embryology and anatomy is important for a meticulous clinical examination and appropriate surgical treatment. This article will review the normal embryology and anatomy of the adolescent female breast and genital tract.

  10. Diarrhoea Caused by Diffuse Metastatic Lobular Breast Cancer

    PubMed Central

    Bakker, Sjoerd F.; Moolenaar, Willem; van Santen, Marije M.; Hendriks, Mathijs P.

    2016-01-01

    A 70-year-old woman with a history of lobular breast cancer presented to our Outpatient Clinic with diarrhoea for the past 3 years. Clinical examination and laboratory research were normal. Colonoscopy showed diffuse mild erythema and a decreased vascular pattern. Biopsies from the ascending colon, transverse colon, and descending colon showed metastases of lobular breast carcinoma. Although gastrointestinal metastases are rare in breast cancer, our case emphasizes the need for further diagnostic efforts in patients with gastrointestinal symptoms and a history of breast carcinoma. PMID:27313924

  11. DNA methylation epigenotypes in breast cancer molecular subtypes

    PubMed Central

    2010-01-01

    Introduction Identification of gene expression-based breast cancer subtypes is considered a critical means of prognostication. Genetic mutations along with epigenetic alterations contribute to gene-expression changes occurring in breast cancer. So far, these epigenetic contributions to sporadic breast cancer subtypes have not been well characterized, and only a limited understanding exists of the epigenetic mechanisms affected in those particular breast cancer subtypes. The present study was undertaken to dissect the breast cancer methylome and to deliver specific epigenotypes associated with particular breast cancer subtypes. Methods By using a microarray approach, we analyzed DNA methylation in regulatory regions of 806 cancer-related genes in 28 breast cancer paired samples. We subsequently performed substantial technical and biologic validation by pyrosequencing, investigating the top qualifying 19 CpG regions in independent cohorts encompassing 47 basal-like, 44 ERBB2+ overexpressing, 48 luminal A, and 48 luminal B paired breast cancer/adjacent tissues. With the all-subset selection method, we identified the most subtype-predictive methylation profiles in multivariable logistic regression analysis. Results The approach efficiently recognized 15 individual CpG loci differentially methylated in breast cancer tumor subtypes. We further identified novel subtype-specific epigenotypes that clearly demonstrate the differences in the methylation profiles of basal-like and human epidermal growth factor 2 (HER2)-overexpressing tumors. Conclusions Our results provide evidence that well-defined DNA methylation profiles enable breast cancer subtype prediction and support the utilization of this biomarker for prognostication and therapeutic stratification of patients with breast cancer. PMID:20920229

  12. Classification of breast computed tomography data

    SciTech Connect

    Nelson, Thomas R.; Cervino, Laura I.; Boone, John M.; Lindfors, Karen K.

    2008-03-15

    Differences in breast tissue composition are important determinants in assessing risk, identifying disease in images and following changes over time. This paper presents an algorithm for tissue classification that separates breast tissue into its three primary constituents of skin, fat and glandular tissue. We have designed and built a dedicated breast CT scanner. Fifty-five normal volunteers and patients with mammographically identified breast lesions were scanned. Breast CT voxel data were filtered using a 5 pt median filter and the image histogram was computed. A two compartment Gaussian fit of histogram data was used to provide an initial estimate of tissue compartments. After histogram analysis, data were input to region-growing algorithms and classified as to belonging to skin, fat or gland based on their value and architectural features. Once tissues were classified, a more detailed analysis of glandular tissue patterns and a more quantitative analysis of breast composition was made. Algorithm performance assessment demonstrated very good or excellent agreement between algorithm and radiologist observers in 97.7% of the segmented data. We observed that even in dense breasts the fraction of glandular tissue seldom exceeded 50%. For most individuals the composition is better characterized as being a 70% (fat)-30% (gland) composition than a 50% (fat)-50% (gland) composition.

  13. Lock 4 View east of lock wall and adjacent ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Lock 4 - View east of lock wall and adjacent roadway built atop tow path. The gate pocket can be seen at center. - Savannah & Ogeechee Barge Canal, Between Ogeechee & Savannah Rivers, Savannah, Chatham County, GA

  14. 14. Charles Acey Cobb standing adjacent to the fish screen ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. Charles Acey Cobb standing adjacent to the fish screen he designed and installed in the Congdon Canal, facing southeast. Photo dates ca. late 1920's. - Congdon Canal, Fish Screen, Naches River, Yakima, Yakima County, WA

  15. 3. View of north side of house facing from adjacent ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. View of north side of house facing from adjacent vacant property. Original wood lap siding and trim is covered by aluminum siding. Recessed side porch is in middle. - 645 South Eighteenth Street (House), Louisville, Jefferson County, KY

  16. View from water showing south facade and adjacent boat slips ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View from water showing south facade and adjacent boat slips (Facility Nos. S375 & S376) - U.S. Naval Base, Pearl Harbor, Boat House, Hornet Avenue at Independence Street, Pearl City, Honolulu County, HI

  17. OBLIQUE OF SOUTHWEST END AND SOUTHEAST SIDE, WITH ADJACENT FACILITY ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    OBLIQUE OF SOUTHWEST END AND SOUTHEAST SIDE, WITH ADJACENT FACILITY 391 IN THE FOREGROUND. - U.S. Naval Base, Pearl Harbor, Joint Intelligence Center, Makalapa Drive in Makalapa Administration Area, Pearl City, Honolulu County, HI

  18. Interior building details of Building A, dungeon cell adjacent to ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Interior building details of Building A, dungeon cell adjacent to northwest cell: granite and brick threshold, poured concrete floors, plastered finished walls, vaulted veiling; northwesterly view - San Quentin State Prison, Building 22, Point San Quentin, San Quentin, Marin County, CA

  19. View of viaduct, looking SE from roof of adjacent parking ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View of viaduct, looking SE from roof of adjacent parking garage. - Mulberry Street Viaduct, Spanning Paxton Creek & Cameron Street (State Route 230) at Mulberry Street (State Route 3012), Harrisburg, Dauphin County, PA

  20. Cement Leakage into Adjacent Vertebral Body Following Percutaneous Vertebroplasty

    PubMed Central

    Park, Jae Hoo; Kim, Hyeun Sung

    2016-01-01

    Percutaneous vertebroplasty (PV) is a minimally invasive procedure for osteoporotic vertebral compression fractures that fail to respond to conventional conservative treatment. It significantly improves intolerable back pain within hours, and has a low complication rate. Although rare, PV is not free of complications, most of which are directly related to cement leakage. Because of its association with new adjacent fracture, the importance of cement leakage into the adjacent disc space is paramount. Here, we report an interesting case of cement leakage into the adjacent upper vertebral body as well as disc space following PV. To the best of our knowledge, there has been no report of cement leakage into the adjacent vertebral body following PV. This rare case is presented along with a review of the literature. PMID:27437018

  1. 2. DETAIL OF CONTROL GATE ADJACENT TO LIFT LOCK NO. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. DETAIL OF CONTROL GATE ADJACENT TO LIFT LOCK NO. 7; THIS CONTROL GATE IS A 1980s RECONSTRUCTION. - Illinois & Michigan Canal, Lift Lock No. 7 & Control Gate, East side of DuPage River, Channahon, Will County, IL

  2. 33. HISTORIC PLAQUE MARKING WHERE JOHNSTON DIED, ADJACENT TO PATHWAY ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    33. HISTORIC PLAQUE MARKING WHERE JOHNSTON DIED, ADJACENT TO PATHWAY WITH CONCRETE CULVERT LEADING NORTH OUT OF RAVINE TOWARD JOHNSTON MEMORIAL SITE. VIEW NW. - Shiloh National Military Park Tour Roads, Shiloh, Hardin County, TN

  3. VIEW OF LAMP FIXTURE (EXTERIOR) ADJACENT TO ENTRANCE AT SOUTHWEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF LAMP FIXTURE (EXTERIOR) ADJACENT TO ENTRANCE AT SOUTHWEST CORNER OF BUILDING 23, FACING NORTH - Roosevelt Base, Auditorium-Gymnasium, West Virginia Street between Richardson & Reeves Avenues, Long Beach, Los Angeles County, CA

  4. VIEW OF NORTHERN AND EASTERN SIDES FROM PARKING LOT ADJACENT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF NORTHERN AND EASTERN SIDES FROM PARKING LOT ADJACENT TO BUILDING 199 (POLICE STATION) - U.S. Naval Base, Pearl Harbor, Post Office, Avenue A near Eleventh Avenue, Pearl City, Honolulu County, HI

  5. 73. PASSAGE ADJACENT TO ROOM 232, EAST WING, SECOND FLOOR, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    73. PASSAGE ADJACENT TO ROOM 232, EAST WING, SECOND FLOOR, LOOKING WEST BY NORTHWEST, SHOWING EASTERNMOST ARCH OF FORMER GREAT HALL NORTH ARCADE - Smithsonian Institution Building, 1000 Jefferson Drive, between Ninth & Twelfth Streets, Southwest, Washington, District of Columbia, DC

  6. 28. TOP VIEW OF CIRCUIT BREAKER ADJACENT TO BRIDGE, CATENARY ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    28. TOP VIEW OF CIRCUIT BREAKER ADJACENT TO BRIDGE, CATENARY ANCHOR BRIDGE 310, COS COB POWER PLANT - New York, New Haven & Hartford Railroad, Automatic Signalization System, Long Island Sound shoreline between Stamford & New Haven, Stamford, Fairfield County, CT

  7. 1. A BRICK AND CONCRETE FAN HOUSING ADJACENT TO ONE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. A BRICK AND CONCRETE FAN HOUSING ADJACENT TO ONE OF THE ADIT OPENINGS (VIEW TO THE NORTH). - Foster Gulch Mine, Fan Housing, Bear Creek 1 mile Southwest of Town of Bear Creek, Red Lodge, Carbon County, MT

  8. GENERAL VIEW OF WAREHOUSE ADJACENT TO BATCH PLANT, LOOKING NORTHWEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF WAREHOUSE ADJACENT TO BATCH PLANT, LOOKING NORTHWEST FROM DREY STREET PLANT, INSIDE WELCOME WALL - Chambers Window Glass Company, Warehouse & Shipping, North of Drey (Nineteenth) Street, West of Constitution Boulevard, Arnold, Westmoreland County, PA

  9. 10. SLATE PATIO ADJACENT TO SOUTH PORCH OF HOUSE, FROM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. SLATE PATIO ADJACENT TO SOUTH PORCH OF HOUSE, FROM SOUTHEAST CORNER OF REAR PORCH. SHED IS VISIBLE IN BACKGROUND. - Butt Valley Dam, Gate Tender's House, Butt Valley Reservoir Road, Caribou, Plumas County, CA

  10. Detail of fire alarm boxes located adjacent to the entrance ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail of fire alarm boxes located adjacent to the entrance of the northwest wing - Mare Island Naval Shipyard, Guard House & Barracks, Railroad Avenue near Eighteenth Street, Vallejo, Solano County, CA

  11. Detail exterior view looking north showing piping system adjacent to ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail exterior view looking north showing piping system adjacent to engine house. Gas cooling system is on far right. - Burnsville Natural Gas Pumping Station, Saratoga Avenue between Little Kanawha River & C&O Railroad line, Burnsville, Braxton County, WV

  12. 1. Ninth Street (west) facade. Adjacent on the north is ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Ninth Street (west) facade. Adjacent on the north is the 9th Street facade of 816 E Street. Both buildings were originally one property. - Riley Building, Rendezvous Adult Magazines & Films, 437 Ninth Street, Northwest, Washington, District of Columbia, DC

  13. 2. THREEQUARTER VIEW FROM ADJACENT ACCESS ROAD SHOWING THREE SPANS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. THREE-QUARTER VIEW FROM ADJACENT ACCESS ROAD SHOWING THREE SPANS AND NORTHWEST APPROACH SPANS, LOOKING SOUTHEAST - Red River Bridge, Spanning Red River at U.S. Highway 82, Garland, Miller County, AR

  14. 31. VAL, DETAIL OF LOADING PLATFORM ADJACENT TO LAUNCHER BRIDGE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    31. VAL, DETAIL OF LOADING PLATFORM ADJACENT TO LAUNCHER BRIDGE LOOKING WEST. - Variable Angle Launcher Complex, Variable Angle Launcher, CA State Highway 39 at Morris Reservior, Azusa, Los Angeles County, CA

  15. Basement, room 23, looking southwest into two adjacent offices with ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Basement, room 23, looking southwest into two adjacent offices with soundproof walls and pedestal flooring - March Air Force Base, Strategic Air Command, Combat Operations Center, 5220 Riverside Drive, Moreno Valley, Riverside County, CA

  16. 52. EASTSIDE PLANT: GENERAL VIEW OF GOVERNOR ADJACENT TO GENERATOR ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    52. EASTSIDE PLANT: GENERAL VIEW OF GOVERNOR ADJACENT TO GENERATOR - American Falls Water, Power & Light Company, Island Power Plant, Snake River, below American Falls Dam, American Falls, Power County, ID

  17. 7. August, 1970 9 ORANGE STREET, ADJACENT TO UNITARIAN CHURCH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. August, 1970 9 ORANGE STREET, ADJACENT TO UNITARIAN CHURCH (NOT IN STUDY AREA) - Orange & Union Streets Neighborhood Study, 8-31 Orange Street, 9-21 Union Street & Stone Alley, Nantucket, Nantucket County, MA

  18. Brick incinerator structure located adjacent to "motor courts." This example ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Brick incinerator structure located adjacent to "motor courts." This example is located between Buildings 26 and 27. Facing northeast - Harbor Hills Housing Project, 26607 Western Avenue, Lomita, Los Angeles County, CA

  19. Adjacent Segment Disease Perspective and Review of the Literature

    PubMed Central

    Saavedra-Pozo, Fanor M.; Deusdara, Renato A. M.; Benzel, Edward C.

    2014-01-01

    Background Adjacent segment disease has become a common topic in spine surgery circles because of the significant increase in fusion surgery in recent years and the development of motion preservation technologies that theoretically should lead to a decrease in this pathology. The purpose of this review is to organize the evidence available in the current literature on this subject. Methods For this literature review, a search was conducted in PubMed with the following keywords: adjacent segment degeneration and disease. Selection, review, and analysis of the literature were completed according to level of evidence. Results The PubMed search identified 850 articles, from which 41 articles were selected and reviewed. The incidence of adjacent segment disease in the cervical spine is close to 3% without a significant statistical difference between surgical techniques (fusion vs arthroplasty). Authors report the incidence of adjacent segment disease in the lumbar spine to range from 2% to 14%. Damage to the posterior ligamentous complex and sagittal imbalances are important risk factors for both degeneration and disease. Conclusion Insufficient evidence exists at this point to support the idea that total disc arthroplasty is superior to fusion procedures in minimizing the incidence of adjacent segment disease. The etiology is most likely multifactorial but it is becoming abundantly clear that adjacent segment disease is not caused by motion segment fusion alone. Fusion plus the presence of abnormal end-fusion alignment appears to be a major factor in creating end-fusion stresses that result in adjacent segment degeneration and subsequent disease. The data presented cast further doubt on previously established rationales for total disc arthroplasty, at least with regard to the effect of total disc arthroplasty on adjacent segment degeneration pathology. PMID:24688337

  20. High-throughput hacking of the methylation patterns in breast cancer by in vitro transcription and thymidine-specific cleavage mass array on MALDI-TOF silico-chip.

    PubMed

    Radpour, Ramin; Haghighi, Mahdi Montazer; Fan, Alex Xiu-Cheng; Torbati, Peyman Mohammadi; Hahn, Sinuhe; Holzgreve, Wolfgang; Zhong, Xiao Yan

    2008-11-01

    Over the last decade, the rapidly expanding interest in the involvement of DNA methylation in developmental mechanisms, human diseases, and malignancies has highlighted the need for an accurate, quantitative, and high-throughput assay. Existing methods are limited and are often too laborious for high-throughput analysis or inadequate for quantitative analysis of methylation. Recently, a MassCLEAVE assay has been developed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to analyze base-specific methylation patterns after bisulfite conversion. To find an efficient and more cost-effective high-throughput method for analyzing the methylation profile in breast cancer, we developed a method that allows for the simultaneous detection of multiple target CpG residues by using thymidine-specific cleavage mass array on matrix-assisted laser desorption/ionization time-of-flight silicon chips. We used this novel quantitative approach for the analysis of DNA methylation patterns of four tumor suppressor genes in 96 breast tissue samples from 48 patients with breast cancer. Each individual contributed a breast cancer specimen and corresponding adjacent normal tissue. We evaluated the accuracy of the approach and implemented critical improvements in experimental design. PMID:19010818

  1. High-throughput hacking of the methylation patterns in breast cancer by in vitro transcription and thymidine-specific cleavage mass array on MALDI-TOF silico-chip.

    PubMed

    Radpour, Ramin; Haghighi, Mahdi Montazer; Fan, Alex Xiu-Cheng; Torbati, Peyman Mohammadi; Hahn, Sinuhe; Holzgreve, Wolfgang; Zhong, Xiao Yan

    2008-11-01

    Over the last decade, the rapidly expanding interest in the involvement of DNA methylation in developmental mechanisms, human diseases, and malignancies has highlighted the need for an accurate, quantitative, and high-throughput assay. Existing methods are limited and are often too laborious for high-throughput analysis or inadequate for quantitative analysis of methylation. Recently, a MassCLEAVE assay has been developed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to analyze base-specific methylation patterns after bisulfite conversion. To find an efficient and more cost-effective high-throughput method for analyzing the methylation profile in breast cancer, we developed a method that allows for the simultaneous detection of multiple target CpG residues by using thymidine-specific cleavage mass array on matrix-assisted laser desorption/ionization time-of-flight silicon chips. We used this novel quantitative approach for the analysis of DNA methylation patterns of four tumor suppressor genes in 96 breast tissue samples from 48 patients with breast cancer. Each individual contributed a breast cancer specimen and corresponding adjacent normal tissue. We evaluated the accuracy of the approach and implemented critical improvements in experimental design.

  2. Numerical modelling of biopotential field for detection of breast tumour.

    PubMed

    Ng, E Y K; Ng, W K; Sim, L S J; Rajendra Acharya, U

    2007-08-01

    Breast cancer is a disease characterised by the uncontrolled growth of abnormal cells. These cancer cells can travel through the body by way of blood or lymph nodes. Previous studies have indicated that, changes in the electrical properties of abnormal breast are more significant compared to the breast normal tissues. In the present study, a simple 2D models of breast (close to realistic), with and without artificially inserted malignant cancer were simulated, based upon electrical activity within the breast. We developed an inhomogeneous female breast model, closer to the actual, by considering a breast as a hemisphere with various layers of unequal thickness in supine condition. In order to determine the potential distribution developed due to a dipole source, isotropic homogeneous conductivity was assigned to each of these compartments and the volume conductor problem was solved using finite element method. Significant changes in the potential distribution were recoded in the malignant and normal breast regions. The surface potential decreases about 0.5%, for the small malignant region of surface area 13 mm(2) (spherical diameter=2mm). And it (surface potential) decreases about 16.4% for large malignant surface area of 615 mm(2) (spherical diameter=14 mm). Hence, the results show that, the sizes of tumours result in the reduction of surface potential and follows a fourth order polynomial equation. Thus, biofield analysis yields promising results in the detection of the breast cancer of various sizes.

  3. Ultrasound-Guided Breast Biopsy

    MedlinePlus

    ... the breast are often detected by physical examination, mammography, or other imaging studies. However, it is not ... full size with caption Related Articles and Media Mammography Ultrasound - Breast Breast Cancer Screening Breast Cancer Treatment ...

  4. Stereotactic (Mammographically Guided) Breast Biopsy

    MedlinePlus

    ... Z Stereotactic Breast Biopsy Stereotactic breast biopsy uses mammography – a specific type of breast imaging that uses ... the breast are often detected by physical examination, mammography, or other imaging studies. However, it is not ...

  5. Hormone Therapy for Breast Cancer

    MedlinePlus

    ... Cancers Breast Cancer Screening Research Hormone Therapy for Breast Cancer On This Page What are hormones? How do ... sensitive breast cancer: Adjuvant therapy for early-stage breast cancer : Research has shown that women treated for early- ...

  6. Stages of Male Breast Cancer

    MedlinePlus

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

  7. Nanomedicine-Mediated Therapies to Target Breast Cancer Stem Cells.

    PubMed

    He, Lili; Gu, Jian; Lim, Lee Y; Yuan, Zhi-Xiang; Mo, Jingxin

    2016-01-01

    Accumulating evidences have suggested the existence of breast cancer stem cells (BCSCs), which possess the potential of both self-renewal and differentiation. The origin of BCSCs might have relationship to the development of normal mammary stem cells. BCSCs are believed to play a key role in the initiation, recurrence and chemo-/radiotherapy resistances of breast cancer. Therefore, elimination of BCSCs is crucial for breast cancer therapy. However, conventional chemo and radiation therapies cannot eradicate BCSCs effectively. Fortunately, nanotechnology holds great potential for specific and efficient anti-BCSCs treatment. "Smart" nanocarriers can distinguish BCSCs from the other breast cancer cells and selectively deliver therapeutic agents to the BCSCs. Emerging findings suggest that BCSCs in breast cancer could be successfully inhibited and even eradicated by functionalized nanomedicines. In this review, we focus on origin of BCSCs, strategies used to target BCSCs, and summarize the nanotechnology-based delivery systems that have been applied for eliminating BCSCs in breast cancer. PMID:27679576

  8. Nanomedicine-Mediated Therapies to Target Breast Cancer Stem Cells.

    PubMed

    He, Lili; Gu, Jian; Lim, Lee Y; Yuan, Zhi-Xiang; Mo, Jingxin

    2016-01-01

    Accumulating evidences have suggested the existence of breast cancer stem cells (BCSCs), which possess the potential of both self-renewal and differentiation. The origin of BCSCs might have relationship to the development of normal mammary stem cells. BCSCs are believed to play a key role in the initiation, recurrence and chemo-/radiotherapy resistances of breast cancer. Therefore, elimination of BCSCs is crucial for breast cancer therapy. However, conventional chemo and radiation therapies cannot eradicate BCSCs effectively. Fortunately, nanotechnology holds great potential for specific and efficient anti-BCSCs treatment. "Smart" nanocarriers can distinguish BCSCs from the other breast cancer cells and selectively deliver therapeutic agents to the BCSCs. Emerging findings suggest that BCSCs in breast cancer could be successfully inhibited and even eradicated by functionalized nanomedicines. In this review, we focus on origin of BCSCs, strategies used to target BCSCs, and summarize the nanotechnology-based delivery systems that have been applied for eliminating BCSCs in breast cancer.

  9. Nanomedicine-Mediated Therapies to Target Breast Cancer Stem Cells

    PubMed Central

    He, Lili; Gu, Jian; Lim, Lee Y.; Yuan, Zhi-xiang; Mo, Jingxin

    2016-01-01

    Accumulating evidences have suggested the existence of breast cancer stem cells (BCSCs), which possess the potential of both self-renewal and differentiation. The origin of BCSCs might have relationship to the development of normal mammary stem cells. BCSCs are believed to play a key role in the initiation, recurrence and chemo-/radiotherapy resistances of breast cancer. Therefore, elimination of BCSCs is crucial for breast cancer therapy. However, conventional chemo and radiation therapies cannot eradicate BCSCs effectively. Fortunately, nanotechnology holds great potential for specific and efficient anti-BCSCs treatment. “Smart” nanocarriers can distinguish BCSCs from the other breast cancer cells and selectively deliver therapeutic agents to the BCSCs. Emerging findings suggest that BCSCs in breast cancer could be successfully inhibited and even eradicated by functionalized nanomedicines. In this review, we focus on origin of BCSCs, strategies used to target BCSCs, and summarize the nanotechnology-based delivery systems that have been applied for eliminating BCSCs in breast cancer.

  10. Older breast cancer survivors' views and preferences for physical activity.

    PubMed

    Whitehead, Sarah; Lavelle, Katrina

    2009-07-01

    Evidence suggests that physical activity improves quality of life and physical functioning among breast cancer patients and survivors. However, previous studies have tended to focus on younger patients, despite higher incidence and lower survival among older breast cancer survivors. In this study we explored physical activity preferences of older breast cancer survivors to inform the development of future targeted interventions. Twenty-nine female breast cancer survivors (1 to 5 years postdiagnosis) aged 59 to 86 (mean 66.54, SD 6.50) took part in either a semistructured interview or a focus group exploring physical activity patterns, motivators, facilitators, barriers, and preferences. The main factors influencing physical activity were body image, weight issues, vitality, mood, and the desire to carry on as normal. Preference was expressed for activities that were gentle, tailored to age and cancer-related abilities, holistic, involving other older breast cancer survivors, and with an instructor who was knowledgeable about both breast cancer and aging.

  11. Mammaglobin, a Valuable Diagnostic Marker for Metastatic Breast Carcinoma

    PubMed Central

    Wang, Zhiqiang; Spaulding, Betsy; Sienko, Anna; Liang, Yiaoming; Li, Hongbao; Nielsen, Gitte; Yub Gong, Gyung; Ro, Jae Y.; “Jim” Zhai, Qihui

    2009-01-01

    Identification of metastasis and occult micrometastases of breast cancer demands sensitive and specific diagnostic markers. In this study, we assessed the utility of a mouse monoclonal antibody to human mammaglobin for one such purpose. Immunohistochemical stains were performed on paraffin-embedded sections from a total of 284 cases, which consisted of primary breast invasive carcinomas (41 cases) with matched metastases to ipsilateral axillary lymph nodes, metastatic breast carcinoma to liver (1 case) and kidney (1 case), non-breast neoplasms (161 cases), and normal human tissues (39 cases). The results showed 31 of the 41 cases of primary breast cancer with axillary lymph node metastases were positive for mammaglobin (76%). In the meantime, we documented expression of mammaglobin in occasional cases of endometrial carcinoma (17%). Our data further validated that mammaglobin is a valuable diagnostic marker for metastatic carcinoma of breast origin, although endometrial carcinoma should be considered as a major differential diagnosis. PMID:19158935

  12. [Evaluation of asymetric implants in breast cancer].

    PubMed

    Fitoussi, A; Couturaud, B; Laki, F; Alran, S; Salmon, R J

    2005-10-01

    Since more than twenty years, methods of breast reconstruction using implants have continued to evolve in order to improve their aesthetic results. Shapes and materials of these implants have also evolved to obtain contours similar to that of the natural opposite breast. Therefore it can be considered that the use of asymmetric implants is the last step in implant technology before using made to measure implants. Asymmetric implants allow obtaining different contours in harmony to the different breast shapes according to the side, left or right, of the reconstructed breast which maximise the naturalness of the result. Such implants have an axis directed towards the exterior and lower part of the chest wall, are wider than high with a thinner part on their inner edge and a concave rear side moulding the curves of the chest wall. In our own experience, we placed more than 500 asymmetric implants. When analysing retrospectively the medical records of 156 patients, no distinctive features were observed when compared to symmetric classic implants in easiness in the surgical procedure or in complications except a slightly higher rate of seroma formation. When compared to usual implants the main benefits of asymmetric implants are: to offer a wider breadth, to slope down gently on their upper and inner sides according to their concave rear side, and therefore to better match subtle curves of a normal breast. Moreover such contours allow a distribution of the volume which fit better to the usual natural breast configuration of patients who underwent surgery for breast carcinoma. At last, such implants are easy to place and a very low rate of secondary rotation has been observed. In summary, for all these reasons, asymmetric implants, can be considered to be the class one in the choice of implants for breast reconstruction after breast surgery. PMID:16198040

  13. The nurse's role in self-breast examination education.

    PubMed

    Nichols, Misty

    2012-01-01

    Do you feel comfortable with your own knowledge of self-breast examination enough to educate a patient? Assessing a patient's compliance of performing self-breast examinations should entail not only if she merely does the examination, but when she is doing them and how she is doing them. There is evidence-based practice that portrays the proper way to perform a self-breast examination. If you, as the primary nurse, are not educated on proper techniques of a self-breast examination, it is your responsibility to provide a resource to the patient that can properly demonstrate this. Women should be educated on the proper way to do a self-breast examination. The first steps should include the ideal time of month to perform the examination. This will allow women to know what is normal breast tissue and what is abnormal to aide in early detection of breast cancer. Utilizing the tools of self-breast examination, yearly mammograms and clinical breast examinations, together with consistency, are the best protection in detecting early breast cancers. PMID:23188144

  14. Breast asymmetry pattern in women with idiopathic scoliosis.

    PubMed

    Cruz, Norma I; Korchin, Leo

    2013-01-01

    Breast asymmetry is frequent in women with idiopathic scoliosis. To understand the pattern of breast asymmetry in these women a clinical study was performed in which 54 female patients with idiopathic scoliosis were evaluated. The information recorded for each patient included: age, weight, height, scoliosis type, Cobb angle, breast measurements, and presence of rib cage asymmetry. Breast volume was calculated using anatomic measurements (anthropomorphic method). The mean age of the group was 25 +/- 7 years. A right convex thoracic curve occurred in 85%, with a mean Cobb angle of 32 +/- 15 degrees. Our study indicated that women with idiopathic scoliosis consistently presented breast asymmetry that followed a predictable pattern. The breast on the side of the convex thoracic scoliosis curve is always smaller in volume (mean difference 59 +/- 39 mi). The affected side also presents a smaller areola, a higher position of the nipple (mean difference 2.2 +/- 1.3 cm) and a higher position of the inframammary fold (mean difference 2.1 +/- 1.4 cm) when compared to the opposite breast. Though the asymmetry is predictable, the degree to which the patient presents these changes does not correlate with the severity of the scoliosis (Cobb angle). We believe that the severity of the asymmetry is a result of the difference between the hypoplastic breast and the normal breasts. In women with very large opposite breasts the asymmetry appears to be worse.

  15. Mortality of passerines adjacent to a North Carolina corn field treated with granular carbofuran.

    USGS Publications Warehouse

    Augspurger, Tom; Smith, Milton R.; Meteyer, Carol U.; Converse, Kathryn A.

    1996-01-01

    Red-winged blackbirds (Agelaius phoeniceus) were collected during an epizootic in southeastern North Carolina (USA). Activity of brain cholinesterase (ChE) was inhibited by 14 to 48% in three of five specimens, and returned to normal levels after incubation. Gastrointestinal tracts were analyzed for 30 anti-ChE agents. Carbofuran, the only compound detected, was present in all specimens at levels from 5.44 to 72.7 μg/g wet weight. Application of granular carbofuran in an adjacent corn field, results of necropsy examinations, and chemical analyses are consistent with a diagnosis of carbofuran poisoning in these specimens.

  16. Assessment of Tumor Heterogeneity, as Evidenced by Gene Expression Profiles, Pathway Activation, and Gene Copy Number, in Patients with Multifocal Invasive Lobular Breast Tumors

    PubMed Central

    Norton, Nadine; Advani, Pooja P.; Serie, Daniel J.; Geiger, Xochiquetzal J.; Necela, Brian M.; Axenfeld, Bianca C.; Kachergus, Jennifer M.; Feathers, Ryan W.; Carr, Jennifer M.; Crook, Julia E.; Moreno-Aspitia, Alvaro; Anastasiadis, Panos Z.; Perez, Edith A.; Thompson, E. Aubrey

    2016-01-01

    Background Invasive lobular carcinoma (ILC) comprises approximately ~10–20% of breast cancers. In general, multifocal/multicentric (MF/MC) breast cancer has been associated with an increased rate of regional lymph node metastases. Tumor heterogeneity between foci represents a largely unstudied source of genomic variation in those rare patients with MF/MC ILC. Methods We characterized gene expression and copy number in 2 or more foci from 11 patients with MF/MC ILC (all ER+, HER2-) and adjacent normal tissue. RNA and DNA were extracted from 3x1.5mm cores from all foci. Gene expression (730 genes) and copy number (80 genes) were measured using Nanostring PanCancer and Cancer CNV panels. Linear mixed models were employed to compare expression in tumor versus normal samples from the same patient, and to assess heterogeneity (variability) in expression among multiple ILC within an individual. Results 35 and 34 genes were upregulated (FC>2) and down-regulated (FC<0.5) respectively in ILC tumor relative to adjacent normal tissue, q<0.05. 9/34 down-regulated genes (FIGF, RELN, PROM1, SFRP1, MMP7, NTRK2, LAMB3, SPRY2, KIT) had changes larger than CDH1, a hallmark of ILC. Copy number changes in these patients were relatively few but consistent across foci within each patient. Amplification of three genes (CCND1, FADD, ORAOV1) at 11q13.3 was present in 2/11 patients in both foci. We observed significant evidence of within-patient between-foci variability (heterogeneity) in gene expression for 466 genes (p<0.05 with FDR 8%), including CDH1, FIGF, RELN, SFRP1, MMP7, NTRK2, LAMB3, SPRY2 and KIT. Conclusions There was substantial variation in gene expression between ILC foci within patients, including known markers of ILC, suggesting an additional level of complexity that should be addressed. PMID:27078887

  17. Breast Imaging Artifacts.

    PubMed

    Odle, Teresa G

    2015-01-01

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

  18. [Male breast cancer].

    PubMed

    Mattson, Johanna; Vehmanen, Leena

    2016-01-01

    Breast cancer is rare in men. Diagnosis of the illness may be delayed due to the fact that the doctor and the patient fail to suspect it. Male breast cancer is treated mainly on the same principles as female breast cancer. A man affected with breast cancer should always be directed to genetic testing, as inherited mutations increasing the risk of developing cancer are more common than in female breast cancer. Most breast cancers in men are hormone receptor positive. Among hormone treatments, the antiestrogen tamoxifen exhibits the best efficacy both in early-state and advanced cases. PMID:27188086

  19. Biomechanics of Artificial Disc Replacements Adjacent to a 2-Level Fusion in 4-Level Hybrid Constructs: An In Vitro Investigation

    PubMed Central

    Liao, Zhenhua; Fogel, Guy R.; Wei, Na; Gu, Hongsheng; Liu, Weiqiang

    2015-01-01

    Background The ideal procedure for multilevel cervical degenerative disc diseases remains controversial. Recent studies on hybrid surgery combining anterior cervical discectomy and fusion (ACDF) and artificial cervical disc replacement (ACDR) for 2-level and 3-level constructs have been reported in the literature. The purpose of this study was to estimate the biomechanics of 3 kinds of 4-level hybrid constructs, which are more likely to be used clinically compared to 4-level arthrodesis. Material/Methods Eighteen human cadaveric spines (C2–T1) were evaluated in different testing conditions: intact, with 3 kinds of 4-level hybrid constructs (hybrid C3–4 ACDR+C4–6 ACDF+C6–7ACDR; hybrid C3–5ACDF+C5–6ACDR+C6–7ACDR; hybrid C3–4ACDR+C4–5ACDR+C5–7ACDF); and 4-level fusion. Results Four-level fusion resulted in significant decrease in the C3–C7 ROM compared with the intact spine. The 3 different 4-level hybrid treatment groups caused only slight change at the instrumented levels compared to intact except for flexion. At the adjacent levels, 4-level fusion resulted in significant increase of contribution of both upper and lower adjacent levels. However, for the 3 hybrid constructs, significant changes of motion increase far lower than 4P at adjacent levels were only noted in partial loading conditions. No destabilizing effect or hypermobility were observed in any 4-level hybrid construct. Conclusions Four-level fusion significantly eliminated motion within the construct and increased motion at the adjacent segments. For all 3 different 4-level hybrid constructs, ACDR normalized motion of the index segment and adjacent segments with no significant hypermobility. Compared with the 4-level ACDF condition, the artificial discs in 4-level hybrid constructs had biomechanical advantages compared to fusion in normalizing adjacent level motion. PMID:26694835

  20. Endocrine therapy of breast cancer

    SciTech Connect

    Cavalli, F.

    1986-01-01

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

  1. Intraoperative radiotherapy for breast cancer

    PubMed Central

    Williams, Norman R.; Pigott, Katharine H.; Brew-Graves, Chris

    2014-01-01

    Intra-operative radiotherapy (IORT) as a treatment for breast cancer is a relatively new technique that is designed to be a replacement for whole breast external beam radiotherapy (EBRT) in selected women suitable for breast-conserving therapy. This article reviews twelve reasons for the use of the technique, with a particular emphasis on targeted intra-operative radiotherapy (TARGIT) which uses X-rays generated from a portable device within the operating theatre immediately after the breast tumour (and surrounding margin of healthy tissue) has been removed. The delivery of a single fraction of radiotherapy directly to the tumour bed at the time of surgery, with the capability of adding EBRT at a later date if required (risk-adaptive technique) is discussed in light of recent results from a large multinational randomised controlled trial comparing TARGIT with EBRT. The technique avoids irradiation of normal tissues such as skin, heart, lungs, ribs and spine, and has been shown to improve cosmetic outcome when compared with EBRT. Beneficial aspects to both institutional and societal economics are discussed, together with evidence demonstrating excellent patient satisfaction and quality of life. There is a discussion of the published evidence regarding the use of IORT twice in the same breast (for new primary cancers) and in patients who would never be considered for EBRT because of their special circumstances (such as the frail, the elderly, or those with collagen vascular disease). Finally, there is a discussion of the role of the TARGIT Academy in developing and sustaining high standards in the use of the technique. PMID:25083504

  2. MicroRNA analysis of breast ductal fluid in breast cancer patients.

    PubMed

    Do Canto, Luisa Matos; Marian, Catalin; Willey, Shawna; Sidawy, Mary; Da Cunha, Patricia A; Rone, Janice D; Li, Xin; Gusev, Yuriy; Haddad, Bassem R

    2016-05-01

    Recent studies suggest that microRNAs show promise as excellent biomarkers for breast cancer; however there is still a high degree of variability between studies making the findings difficult to interpret. In addition to blood, ductal lavage (DL) and nipple aspirate fluids represent an excellent opportunity for biomarker detection because they can be obtained in a less invasive manner than biopsies and circumvent the limitations of evaluating blood biomarkers with regards to tissue of origin specificity. In this study, we have investigated for the first time, through a real-time PCR array, the expression of 742 miRNAs in the ductal lavage fluid collected from 22 women with unilateral breast tumors. We identified 17 differentially expressed miRNAs between tumor and paired normal samples from patients with ductal breast carcinoma. Most of these miRNAs have various roles in breast cancer tumorigenesis, invasion and metastasis, therapeutic response, or are associated with several clinical and pathological characteristics of breast tumors. Moreover, some miRNAs were also detected in other biological fluids of breast cancer patients such as serum (miR-23b, -133b, -181a, 338-3p, -625), plasma (miR-200a), and breast milk (miR-181a). A systems biology analysis of these differentially expressed miRNAs points out possible pathways and cellular processes previously described as having an important role in breast cancer such as Wnt, ErbB, MAPK, TGF-β, mTOR, PI3K-Akt, p53 signaling pathways. We also observed a difference in the miRNA expression with respect to the histological type of the tumors. In conclusion, our findings suggest that miRNA analysis of breast ductal fluid is feasible and potentially very useful for the detection of breast cancer.

  3. Upregulation of ATM in sclerosing adenosis of the breast.

    PubMed Central

    Clarke, R A; Kairouz, R; Watters, D; Lavin, M F; Kearsley, J H; Lee, C S

    1998-01-01

    The gene mutated in ataxia telangiectasia (ATM) has an established tumour suppressor role in breast cancer. ATM appears to be expressed in most normal cells, including breast epithelium, where it has been postulated to have a nuclear role in cell cycle regulation following DNA damage. However, ATM is not upregulated after DNA damage. In this study, we demonstrate an absence of immunohistologically detectable levels of ATM in the normally quiescent myoepithelial cells that line normal breast ducts. This contrasts dramatically with the significant expression of ATM in the proliferative myoepithelium of sclerosing adenosis (n = 7). This upregulation of ATM suggests that ATM expression is coupled to the proliferative status of the myoepithelium. Our results also indicate that there are factors other than ATM gene mutations that can dramatically influence ATM expression in the breast and that these factors should be considered for their possible implications in carcinogenesis. PMID:9893751

  4. Recurrent fusion transcripts detected by whole-transcriptome sequencing of 120 primary breast cancer samples.

    PubMed

    Kim, Jisun; Kim, Sehwan; Ko, Seyoon; In, Yong-ho; Moon, Hyeong-Gon; Ahn, Soo Kyung; Kim, Min Kyoon; Lee, Minju; Hwang, Jin-Ha; Ju, Young Seok; Kim, Jong-Il; Noh, Dong-Young; Kim, Sun; Park, Jung-Hoon; Rhee, Hwanseok; Kim, Sunghoon; Han, Wonshik

    2015-11-01

    Relatively few recurrent gene fusion events have been associated with breast cancer to date. In an effort to uncover novel fusion transcripts, we performed whole-transcriptome sequencing of 120 fresh-frozen primary breast cancer samples and five adjacent normal breast tissues using the Illumina HiSeq2000 platform. Three different fusion-detecting tools (deFuse, Chimerascan, and TopHatFusion) were used, and the results were compared. These tools detected 3,831, 6,630 and 516 fusion transcripts (FTs) overall. We primarily focused on the results obtained using the deFuse software. More FTs were identified from HER2 subtype breast cancer samples than from the luminal or triple-negative subtypes (P < 0.05). Seventy fusion candidates were selected for validation, and 32 (45.7%) were confirmed by RT-PCR and Sanger sequencing. Of the validated fusions, six were recurrent (found in 2 or more samples), three were in-frame (PRDX1-AKR1A1, TACSTD2-OMA1, and C2CD2-TFF1) and three were off-frame (CEACAM7-CEACAM6, CYP4X1-CYP4Z2P, and EEF1DP3-FRY). Notably, the novel read-through fusion, EEF1DP3-FRY, was identified and validated in 6.7% (8/120) of the breast cancer samples. This off-frame fusion results in early truncation of the FRY gene, which plays a key role in the structural integrity during mitosis. Three previously reported fusions, PPP1R1B-STARD3, MFGE8-HAPL, and ETV6-NTRK3, were detected in 8.3, 3.3, and 0.8% of the 120 samples, respectively, by both deFuse and Chimerascan. The recently reported MAGI3-AKT3 fusion was not detected in our analysis. Although future work will be needed to examine the biological significance of our new findings, we identified a number of novel fusions and confirmed some previously reported fusions. PMID:26227178

  5. A Physical Mechanism and Global Quantification of Breast Cancer

    PubMed Central

    Yu, Chong; Wang, Jin

    2016-01-01

    Initiation and progression of cancer depend on many factors. Those on the genetic level are often considered crucial. To gain insight into the physical mechanisms of breast cancer, we construct a gene regulatory network (GRN) which reflects both genetic and environmental aspects of breast cancer. The construction of the GRN is based on available experimental data. Three basins of attraction, representing the normal, premalignant and cancer states respectively, were found on the phenotypic landscape. The progression of breast cancer can be seen as switching transitions between different state basins. We quantified the stabilities and kinetic paths of the three state basins to uncover the biological process of breast cancer formation. The gene expression levels at each state were obtained, which can be tested directly in experiments. Furthermore, by performing global sensitivity analysis on the landscape topography, six key genes (HER2, MDM2, TP53, BRCA1, ATM, CDK2) and four regulations (HER2⊣TP53, CDK2⊣BRCA1, ATM→MDM2, TP53→ATM) were identified as being critical for breast cancer. Interestingly, HER2 and MDM2 are the most popular targets for treating breast cancer. BRCA1 and TP53 are the most important oncogene of breast cancer and tumor suppressor gene, respectively. This further validates the feasibility of our model and the reliability of our prediction results. The regulation ATM→MDM2 has been extensive studied on DNA damage but not on breast cancer. We notice the importance of ATM→MDM2 on breast cancer. Previous studies of breast cancer have often focused on individual genes and the anti-cancer drugs are mainly used to target the individual genes. Our results show that the network-based strategy is more effective on treating breast cancer. The landscape approach serves as a new strategy for analyzing breast cancer on both the genetic and epigenetic levels and can help on designing network based medicine for breast cancer. PMID:27410227

  6. Best Merge Region Growing Segmentation with Integrated Non-Adjacent Region Object Aggregation

    NASA Technical Reports Server (NTRS)

    Tilton, James C.; Tarabalka, Yuliya; Montesano, Paul M.; Gofman, Emanuel

    2012-01-01

    Best merge region growing normally produces segmentations with closed connected region objects. Recognizing that spectrally similar objects often appear in spatially separate locations, we present an approach for tightly integrating best merge region growing with non-adjacent region object aggregation, which we call Hierarchical Segmentation or HSeg. However, the original implementation of non-adjacent region object aggregation in HSeg required excessive computing time even for moderately sized images because of the required intercomparison of each region with all other regions. This problem was previously addressed by a recursive approximation of HSeg, called RHSeg. In this paper we introduce a refined implementation of non-adjacent region object aggregation in HSeg that reduces the computational requirements of HSeg without resorting to the recursive approximation. In this refinement, HSeg s region inter-comparisons among non-adjacent regions are limited to regions of a dynamically determined minimum size. We show that this refined version of HSeg can process moderately sized images in about the same amount of time as RHSeg incorporating the original HSeg. Nonetheless, RHSeg is still required for processing very large images due to its lower computer memory requirements and amenability to parallel processing. We then note a limitation of RHSeg with the original HSeg for high spatial resolution images, and show how incorporating the refined HSeg into RHSeg overcomes this limitation. The quality of the image segmentations produced by the refined HSeg is then compared with other available best merge segmentation approaches. Finally, we comment on the unique nature of the hierarchical segmentations produced by HSeg.

  7. Laplacian versus adjacency matrix in quantum walk search

    NASA Astrophysics Data System (ADS)

    Wong, Thomas G.; Tarrataca, Luís; Nahimov, Nikolay

    2016-10-01

    A quantum particle evolving by Schrödinger's equation contains, from the kinetic energy of the particle, a term in its Hamiltonian proportional to Laplace's operator. In discrete space, this is replaced by the discrete or graph Laplacian, which gives rise to a continuous-time quantum walk. Besides this natural definition, some quantum walk algorithms instead use the adjacency matrix to effect the walk. While this is equivalent to the Laplacian for regular graphs, it is different for non-regular graphs and is thus an inequivalent quantum walk. We algorithmically explore this distinction by analyzing search on the complete bipartite graph with multiple marked vertices, using both the Laplacian and adjacency matrix. The two walks differ qualitatively and quantitatively in their required jumping rate, runtime, sampling of marked vertices, and in what constitutes a natural initial state. Thus the choice of the Laplacian or adjacency matrix to effect the walk has important algorithmic consequences.

  8. Laplacian versus adjacency matrix in quantum walk search

    NASA Astrophysics Data System (ADS)

    Wong, Thomas G.; Tarrataca, Luís; Nahimov, Nikolay

    2016-06-01

    A quantum particle evolving by Schrödinger's equation contains, from the kinetic energy of the particle, a term in its Hamiltonian proportional to Laplace's operator. In discrete space, this is replaced by the discrete or graph Laplacian, which gives rise to a continuous-time quantum walk. Besides this natural definition, some quantum walk algorithms instead use the adjacency matrix to effect the walk. While this is equivalent to the Laplacian for regular graphs, it is different for non-regular graphs and is thus an inequivalent quantum walk. We algorithmically explore this distinction by analyzing search on the complete bipartite graph with multiple marked vertices, using both the Laplacian and adjacency matrix. The two walks differ qualitatively and quantitatively in their required jumping rate, runtime, sampling of marked vertices, and in what constitutes a natural initial state. Thus the choice of the Laplacian or adjacency matrix to effect the walk has important algorithmic consequences.

  9. Differential expression of matrix metalloproteinase-13 in association with invasion of breast cancer.

    PubMed

    Kotepui, Manas; Punsawad, Chuchard; Chupeerach, Chaowanee; Songsri, Apiram; Charoenkijkajorn, Lek; Petmitr, Songsak

    2016-01-01

    Matrix metalloproteinase-13 (MMP-13) has a potential role in tumour invasion and metastasis. However, its relevance to the prognosis of human breast cancer is poorly understood. The aim of this study is to investigate the expression patterns of MMP-13 protein and to determine its prognostic value in breast cancer, and to define its relation to the clinicopathological features. Immunohistochemistry analysis of MMP-13 was performed on formalin-fixed, paraffin-embedded sections of cancerous breast tissue (n = 76) and normal breast tissue (n = 20), all of which had clinicopathological information available. Based on the principle of immunoreactivity, the detection of MMP-13 on breast tissue was conducted using monoclonal antibodies against MMP-13. A semi-quantitative scoring system was used to assess the presence of, as well as the cellular localisation of MMP-13. MMP-13 expression was significantly greater in the cancerous breast tissues in comparison to those of normal breast tissues. In addition, high levels of MMP-13 expression were also found to be related to the positive detection of breast cancer cells in lymph nodes-amongst breast cancer patients. The results of this study showed that MMP-13 was frequently present in breast tumours, especially when tumours were accompanied by positive breast cancer cell detection in lymph nodes. This suggests that MMP-13 plays a potentially significant role in breast cancer invasion and metastasis. PMID:27647987

  10. Differential expression of matrix metalloproteinase-13 in association with invasion of breast cancer

    PubMed Central

    Punsawad, Chuchard; Chupeerach, Chaowanee; Songsri, Apiram; Charoenkijkajorn, Lek; Petmitr, Songsak

    2016-01-01

    Matrix metalloproteinase-13 (MMP-13) has a potential role in tumour invasion and metastasis. However, its relevance to the prognosis of human breast cancer is poorly understood. The aim of this study is to investigate the expression patterns of MMP-13 protein and to determine its prognostic value in breast cancer, and to define its relation to the clinicopathological features. Immunohistochemistry analysis of MMP-13 was performed on formalin-fixed, paraffin-embedded sections of cancerous breast tissue (n = 76) and normal breast tissue (n = 20), all of which had clinicopathological information available. Based on the principle of immunoreactivity, the detection of MMP-13 on breast tissue was conducted using monoclonal antibodies against MMP-13. A semi-quantitative scoring system was used to assess the presence of, as well as the cellular localisation of MMP-13. MMP-13 expression was significantly greater in the cancerous breast tissues in comparison to those of normal breast tissues. In addition, high levels of MMP-13 expression were also found to be related to the positive detection of breast cancer cells in lymph nodes-amongst breast cancer patients. The results of this study showed that MMP-13 was frequently present in breast tumours, especially when tumours were accompanied by positive breast cancer cell detection in lymph nodes. This suggests that MMP-13 plays a potentially significant role in breast cancer invasion and metastasis. PMID:27647987

  11. Breast ductal carcinoma in situ presenting as recurrent non-puerperal mastitis: case report and literature review.

    PubMed

    Liong, Yee Vonne; Hong, Ga Sze; Teo, Jennifer Gek Choo; Lim, Geok Hoon

    2013-08-07

    Breast ductal carcinoma in situ (DCIS) is a preinvasive form of breast cancer. It typically presents as microcalcifications which are picked up on screening mammogram. We report an atypical case of breast DCIS presenting with recurrent non-puerperal mastitis with a normal mammogram and perform a literature review.

  12. Descriptive texture analyses of cooked broiler breast fillets with the wooden condition after fresh and frozen storage

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to evaluate the effects of the wooden breast condition on the texture of cooked broiler breast fillets (Pectoralis major) after fresh and frozen storage. Texture characteristics of normal (NORM) and severe wooden breast (WB) fillets were studied by both sensory descr...

  13. Breast augmentation surgery

    MedlinePlus

    ... a change in the shape of your breast, hardening of breast tissue, or some pain. Emotional risks ... starting 5 days after surgery. Massaging helps reduce hardening of the capsule that surrounds the implant. Ask ...

  14. Screening for Breast Problems

    MedlinePlus

    f AQ FREQUENTLY ASKED QUESTIONS FAQ178 GYNECOLOGIC PROBLEMS Mammography and Other Screening Tests for Breast Problems • What ... used to screen for breast problems? • What is mammography? • Why is mammography done? • When should I start ...

  15. MRI of the Breast

    MedlinePlus

    ... as a supplemental tool to breast screening with mammography or ultrasound. It may be used to screen ... following diagnosis, or further evaluate abnormalities seen on mammography. Breast MRI does not use ionizing radiation, and ...

  16. Breast Cancer: Treatment Options

    MedlinePlus

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

  17. Breast Reconstruction Alternatives

    MedlinePlus

    ... facts before submitting any insurance claims. For a list of companies that sell breast prostheses and other accessories, see Breast Prostheses and Hair Loss Accessories List . Going flat Some women who do not have ...

  18. Breastfeeding and Breast Milk

    MedlinePlus

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

  19. Stages of Breast Cancer

    MedlinePlus

    ... to treat breast cancer. Internal radiation therapy with strontium-89 (a radionuclide ) is used to relieve bone pain ... breast cancer that has spread to the bones. Strontium-89 is injected into a vein and travels to ...

  20. Breast Cancer Treatment

    MedlinePlus

    ... to treat breast cancer. Internal radiation therapy with strontium-89 (a radionuclide ) is used to relieve bone pain ... breast cancer that has spread to the bones. Strontium-89 is injected into a vein and travels to ...

  1. Breast cancer staging

    MedlinePlus

    Doctors use 7 main stages to describe breast cancer. Stage 0, also called carcinoma in situ. This is cancer that is confined to the lobules or ducts in the breast. It has not spread to surrounding tissue. ...

  2. Breast Reconstruction and Prosthesis

    MedlinePlus

    ... feel of the breast after a mastectomy. A plastic surgeon can do it at the same time ... want breast reconstruction. • Have you talked with your plastic surgeon about your options? You may not be ...

  3. Breast cancer risk in metabolically healthy but overweight postmenopausal women.

    PubMed

    Gunter, Marc J; Xie, Xianhong; Xue, Xiaonan; Kabat, Geoffrey C; Rohan, Thomas E; Wassertheil-Smoller, Sylvia; Ho, Gloria Y F; Wylie-Rosett, Judith; Greco, Theresa; Yu, Herbert; Beasley, Jeannette; Strickler, Howard D

    2015-01-15

    Adiposity is an established risk factor for postmenopausal breast cancer. Recent data suggest that high insulin levels in overweight women may play a major role in this relationship, due to insulin's mitogenic/antiapoptotic activity. However, whether overweight women who are metabolically healthy (i.e., normal insulin sensitivity) have elevated risk of breast cancer is unknown. We investigated whether overweight women with normal insulin sensitivity [i.e., homeostasis model assessment of insulin resistance (HOMA-IR) index, or fasting insulin level, within the lowest quartile (q1)] have increased breast cancer risk. Subjects were incident breast cancer cases (N = 497) and a subcohort (N = 2,830) of Women's Health Initiative (WHI) participants with available fasting insulin and glucose levels. In multivariate Cox models, metabolically healthy overweight women, defined using HOMA-IR, were not at elevated risk of breast cancer compared with metabolically healthy normal weight women [HRHOMA-IR, 0.96; 95% confidence interval (CI), 0.64-1.42]. In contrast, the risk among women with high (q3-4) HOMA-IRs was elevated whether they were overweight (HRHOMA-IR, 1.76; 95% CI, 1.19-2.60) or normal weight (HRHOMA-IR, 1.80; 95% CI, 0.88-3.70). Similarly, using fasting insulin to define metabolic health, metabolically unhealthy women (insulin q3-4) were at higher risk of breast cancer regardless of whether they were normal weight (HRinsulin, 2.06; 95% CI, 1.01-4.22) or overweight (HRinsulin, 2.01; 95% CI, 1.35-2.99), whereas metabolically healthy overweight women did not have significantly increased risk of breast cancer (HRinsulin, 0.96; 95% CI, 0.64-1.42) relative to metabolically healthy normal weight women. Metabolic health (e.g., HOMA-IR or fasting insulin) may be more biologically relevant and more useful for breast cancer risk stratification than adiposity per se. PMID:25593034

  4. Breast cancer risk in metabolically healthy but overweight postmenopausal women.

    PubMed

    Gunter, Marc J; Xie, Xianhong; Xue, Xiaonan; Kabat, Geoffrey C; Rohan, Thomas E; Wassertheil-Smoller, Sylvia; Ho, Gloria Y F; Wylie-Rosett, Judith; Greco, Theresa; Yu, Herbert; Beasley, Jeannette; Strickler, Howard D

    2015-01-15

    Adiposity is an established risk factor for postmenopausal breast cancer. Recent data suggest that high insulin levels in overweight women may play a major role in this relationship, due to insulin's mitogenic/antiapoptotic activity. However, whether overweight women who are metabolically healthy (i.e., normal insulin sensitivity) have elevated risk of breast cancer is unknown. We investigated whether overweight women with normal insulin sensitivity [i.e., homeostasis model assessment of insulin resistance (HOMA-IR) index, or fasting insulin level, within the lowest quartile (q1)] have increased breast cancer risk. Subjects were incident breast cancer cases (N = 497) and a subcohort (N = 2,830) of Women's Health Initiative (WHI) participants with available fasting insulin and glucose levels. In multivariate Cox models, metabolically healthy overweight women, defined using HOMA-IR, were not at elevated risk of breast cancer compared with metabolically healthy normal weight women [HRHOMA-IR, 0.96; 95% confidence interval (CI), 0.64-1.42]. In contrast, the risk among women with high (q3-4) HOMA-IRs was elevated whether they were overweight (HRHOMA-IR, 1.76; 95% CI, 1.19-2.60) or normal weight (HRHOMA-IR, 1.80; 95% CI, 0.88-3.70). Similarly, using fasting insulin to define metabolic health, metabolically unhealthy women (insulin q3-4) were at higher risk of breast cancer regardless of whether they were normal weight (HRinsulin, 2.06; 95% CI, 1.01-4.22) or overweight (HRinsulin, 2.01; 95% CI, 1.35-2.99), whereas metabolically healthy overweight women did not have significantly increased risk of breast cancer (HRinsulin, 0.96; 95% CI, 0.64-1.42) relative to metabolically healthy normal weight women. Metabolic health (e.g., HOMA-IR or fasting insulin) may be more biologically relevant and more useful for breast cancer risk stratification than adiposity per se.

  5. On the Adjacent Eccentric Distance Sum Index of Graphs

    PubMed Central

    Qu, Hui; Cao, Shujuan

    2015-01-01

    For a given graph G, ε(v) and deg(v) denote the eccentricity and the degree of the vertex v in G, respectively. The adjacent eccentric distance sum index of a graph G is defined as ξsv(G)=∑v∈V(G)ε(v)D(v)deg(v), where D(v)=∑u∈V(G)d(u,v) is the sum of all distances from the vertex v. In this paper we derive some bounds for the adjacent eccentric distance sum index in terms of some graph parameters, such as independence number, covering number, vertex connectivity, chromatic number, diameter and some other graph topological indices. PMID:26091095

  6. Nonlinear spin wave coupling in adjacent magnonic crystals

    NASA Astrophysics Data System (ADS)

    Sadovnikov, A. V.; Beginin, E. N.; Morozova, M. A.; Sharaevskii, Yu. P.; Grishin, S. V.; Sheshukova, S. E.; Nikitov, S. A.

    2016-07-01

    We have experimentally studied the coupling of spin waves in the adjacent magnonic crystals. Space- and time-resolved Brillouin light-scattering spectroscopy is used to demonstrate the frequency and intensity dependent spin-wave energy exchange between the side-coupled magnonic crystals. The experiments and the numerical simulation of spin wave propagation in the coupled periodic structures show that the nonlinear phase shift of spin wave in the adjacent magnonic crystals leads to the nonlinear switching regime at the frequencies near the forbidden magnonic gap. The proposed side-coupled magnonic crystals represent a significant advance towards the all-magnonic signal processing in the integrated magnonic circuits.

  7. Breast Augmentation With Autologous Fat Injection

    PubMed Central

    Li, Fa-Cheng; Chen, Bing; Cheng, Lin

    2014-01-01

    Introduction Autologous fat transplantation has attracted great interest in breast augmentation for cosmetic purpose. In the present study, we reported our experience in fat grafting in breast in 105 cases, and some detailed procedure concerning efficacy and safety of grafting was evaluated. Methods Fat was harvested using 20-mL syringe attached to a 3-hole blunt cannula in a diameter not beyond 3 mm. After washing with cool normal saline to remove blood, the fat was managed with open method using cotton towel as a platform for concentration fat tissue and separating them from fluids, oil, and debris. A 14-gauge, 1-hole blunt cannula was used to place the fat through 3-mm incision on inframammary fold. The fat was infiltrated into the breast from deep to superficial subcutaneous plane. Results Between July 2002 and August 2010, 105 patients have undergone this procedure. The age distribution of the patients ranged from 18 to 45 years, with a mean of 31.3 years. Grafted fat volume has ranged from 120 to 250 mL (average, 205 mL) per breast per session. All women had a significant improvement in their breast size and shape postoperatively, and the breasts were soft and natural in appearance. Conclusions Liposuction and autologous fat transplantation is a suitable approach for augmentation mammaplasty. PMID:25003461

  8. Exposure to Bovine Leukemia Virus Is Associated with Breast Cancer: A Case-Control Study

    PubMed Central

    Buehring, Gertrude Case; Shen, Hua Min; Jensen, Hanne M.; Jin, Diana L.; Hudes, Mark; Block, Gladys

    2015-01-01

    Background Age, reproductive history, hormones, genetics, and lifestyle are known risk factors for breast cancer, but the agents that initiate cellular changes from normal to malignant are not understood. We previously detected bovine leukemia virus (BLV), a common oncogenic virus of cattle, in the breast epithelium of humans. The objective of this study was to determine whether the presence of BLV DNA in human mammary epithelium is associated with breast cancer. Methods This was a case-control study of archival formalin fixed paraffin embedded breast tissues from 239 donors, received 2002–2008 from the Cooperative Human Tissue Network. Case definition as breast cancer versus normal (women with no history of breast cancer) was established through medical records and examination of tissues by an anatomical pathologist. Breast exposure to BLV was determined by in situ-PCR detection of a biomarker, BLV DNA, localized within mammary epithelium. Results The frequency of BLV DNA in mammary epithelium from women with breast cancer (59%) was significantly higher than in normal controls (29%) (multiply- adjusted odds ratio = 3.07, confidence interval = 1.66–5.69, p = .0004, attributable risk = 37%). In women with premalignant breast changes the frequency of BLV DNA was intermediate (38%) between that of women with breast cancer and normal controls (p for trend < .001). Conclusions Among the specimens in this study, the presence of amplified BLV DNA was significantly associated with breast cancer. The odds ratio magnitude was comparable to those of well-established breast cancer risk factors related to reproductive history, hormones, and lifestyle and was exceeded only by risk factors related to genetics (familial breast cancer), high dose ionizing radiation, and age. These findings have the potential for primary and secondary prevention of breast cancer. PMID:26332838

  9. Application of Raman Spectroscopy and Infrared Spectroscopy in the Identification of Breast Cancer.

    PubMed

    Depciuch, Joanna; Kaznowska, Ewa; Zawlik, Izabela; Wojnarowska, Renata; Cholewa, Marian; Heraud, Philip; Cebulski, Józef

    2016-02-01

    Raman spectroscopy and infrared (IR) spectroscopy are both techniques that allow for the investigation of vibrating chemical particles. These techniques provide information not only about chemical particles through the identification of functional groups and spectral analysis of so-called "fingerprints", these methods allow for the qualitative and quantitative analyses of chemical substances in the sample. Both of these spectral techniques are frequently being used in biology and medicine in diagnosing illnesses and monitoring methods of therapy. The type of breast cancer found in woman is often a malignant tumor, causing 1.38 million new cases of breast cancer and 458 000 deaths in the world in 2013. The most important risk factors for breast cancer development are: sex, age, family history, specific benign breast conditions in the breast, ionizing radiation, and lifestyle. The main purpose of breast cancer screening tests is to establish early diagnostics and to apply proper treatment. Diagnoses of breast cancer are based on: (1) physical techniques (e.g., ultrasonography, mammography, elastography, magnetic resonance, positron emission tomography [PET]); (2) histopathological techniques; (3) biological techniques; and (4) optical techniques (e.g., photo acoustic imaging, fluorescence tomography). However, none of these techniques provides unique or especially revealing answers. The aim of our study is comparative spectroscopic measurements on patients with the following: normal non-cancerous breast tissue; breast cancer tissues before chemotherapy; breast cancer tissues after chemotherapy; and normal breast tissues received around the cancerous breast region. Spectra collected from breast cancer patients shows changes in amounts of carotenoids and fats. We also observed changes in carbohydrate and protein levels (e.g., lack of amino acids, changes in the concentration of amino acids, structural changes) in comparison with normal breast tissues. This fact

  10. Application of Raman Spectroscopy and Infrared Spectroscopy in the Identification of Breast Cancer.

    PubMed

    Depciuch, Joanna; Kaznowska, Ewa; Zawlik, Izabela; Wojnarowska, Renata; Cholewa, Marian; Heraud, Philip; Cebulski, Józef

    2016-02-01

    Raman spectroscopy and infrared (IR) spectroscopy are both techniques that allow for the investigation of vibrating chemical particles. These techniques provide information not only about chemical particles through the identification of functional groups and spectral analysis of so-called "fingerprints", these methods allow for the qualitative and quantitative analyses of chemical substances in the sample. Both of these spectral techniques are frequently being used in biology and medicine in diagnosing illnesses and monitoring methods of therapy. The type of breast cancer found in woman is often a malignant tumor, causing 1.38 million new cases of breast cancer and 458 000 deaths in the world in 2013. The most important risk factors for breast cancer development are: sex, age, family history, specific benign breast conditions in the breast, ionizing radiation, and lifestyle. The main purpose of breast cancer screening tests is to establish early diagnostics and to apply proper treatment. Diagnoses of breast cancer are based on: (1) physical techniques (e.g., ultrasonography, mammography, elastography, magnetic resonance, positron emission tomography [PET]); (2) histopathological techniques; (3) biological techniques; and (4) optical techniques (e.g., photo acoustic imaging, fluorescence tomography). However, none of these techniques provides unique or especially revealing answers. The aim of our study is comparative spectroscopic measurements on patients with the following: normal non-cancerous breast tissue; breast cancer tissues before chemotherapy; breast cancer tissues after chemotherapy; and normal breast tissues received around the cancerous breast region. Spectra collected from breast cancer patients shows changes in amounts of carotenoids and fats. We also observed changes in carbohydrate and protein levels (e.g., lack of amino acids, changes in the concentration of amino acids, structural changes) in comparison with normal breast tissues. This fact

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

    ClinicalTrials.gov

    2015-08-27

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

  12. Alignment of sources and detectors on breast surface for noncontact diffuse correlation tomography of breast tumors

    PubMed Central

    Huang, Chong; Lin, Yu; He, Lian; Irwin, Daniel; Szabunio, Margaret M.; Yu, Guoqiang

    2016-01-01

    Noncontact diffuse correlation tomography (ncDCT) is an emerging technology for 3D imaging of deep tissue blood flow distribution without distorting hemodynamic properties. To adapt the ncDCT for imaging in vivo breast tumors, we designed a motorized ncDCT probe to scan over the breast surface. A computer-aided design (CAD)-based approach was proposed to create solid volume mesh from arbitrary breast surface obtained by a commercial 3D camera. The sources and detectors of ncDCT were aligned on the breast surface through ray tracing to mimic the ncDCT scanning with CAD software. The generated breast volume mesh along with the boundary data of ncDCT at the aligned source and detector pairs were used for finite-element-method-based flow image reconstruction. We evaluated the accuracy of source alignments on mannequin and human breasts; largest alignment errors were less than 10% in both tangential and radial directions of scanning. The impact of alignment errors (assigned 10%) on the tumor reconstruction was estimated using computer simulations. The deviations of simulated tumor location and blood flow contrast resulted from the alignment errors were 0.77 mm (less than the node distance of 1 mm) and 1%, respectively, which result in minor impact on flow image reconstruction. Finally, a case study on a human breast tumor was conducted and a tumor-to-normal flow contrast was reconstructed, demonstrating the feasibility of ncDCT in clinical application. PMID:26479823

  13. Normal Pressure Hydrocephalus

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Normal Pressure Hydrocephalus Information Page Synonym(s): Hydrocephalus - Normal Pressure Table ... Español Additional resources from MedlinePlus What is Normal Pressure Hydrocephalus? Normal pressure hydrocephalus (NPH) is an abnormal ...

  14. The classification of normal screening mammograms

    NASA Astrophysics Data System (ADS)

    Ang, Zoey Z. Y.; Rawashdeh, Mohammad A.; Heard, Robert; Brennan, Patrick C.; Lee, Warwick; Lewis, Sarah J.

    2016-03-01

    Rationale and objectives: To understand how breast screen readers classify the difficulty of normal screening mammograms using common lexicon describing normal appearances. Cases were also assessed on their suitability for a single reader strategy. Materials and Methods: 15 breast readers were asked to interpret a test set of 29 normal screening mammogram cases and classify them by rating the difficulty of the case on a five-point Likert scale, identifying the salient features and assessing their suitability for single reading. Using the False Positive Fractions from a previous study, the 29 cases were classified into 10 "low", 10 "medium" and nine "high" difficulties. Data was analyzed with descriptive statistics. Spearman's correlation was used to test the strength of association between the difficulty of the cases and the readers' recommendation for single reading strategy. Results: The ratings from readers in this study corresponded to the known difficulty level of cases for the 'low' and 'high' difficulty cases. Uniform ductal pattern and density, symmetrical mammographic features and the absence of micro-calcifications were the main reasons associated with 'low' difficulty cases. The 'high' difficulty cases were described as having `dense breasts'. There was a statistically significant negative correlation between the difficulty of the cases and readers' recommendation for single reading (r = -0.475, P = 0.009). Conclusion: The findings demonstrated potential relationships between certain mammographic features and the difficulty for readers to classify mammograms as 'normal'. The standard Australian practice of double reading was deemed more suitable for most cases. There was an inverse moderate association between the difficulty of the cases and the recommendations for single reading.

  15. Broccoli Sprout Extract in Treating Patients With Breast Cancer

    ClinicalTrials.gov

    2016-08-16

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

  16. Sexuality after breast cancer: a review.

    PubMed

    Gilbert, Emilee; Emilee, Gilbert; Ussher, J M; Perz, J

    2010-08-01

    It is widely recognised that women's sexuality can be particularly complex after breast cancer, with sexual changes often becoming the most problematic aspect of a woman's life. The impact of such changes can last for many years after successful treatment, and can be associated with serious physical and emotional side-effects. The objective of this paper is to review research on breast cancer and sexuality from the years 1998 to 2010. Research has documented a range of physical changes to a woman's sexuality following breast cancer, including disturbances to sexual functioning, as well as disruptions to sexual arousal, lubrication, orgasm, sexual desire, and sexual pleasure, resulting from chemotherapy, chemically induced menopause, tamoxifen, and breast cancer surgery. Women's intrapsychic experience of changes to sexuality includes a fear of loss of fertility, negative body image, feelings of sexual unattractiveness, loss of femininity, depression and anxiety, as well as alterations to a sense of sexual self. The discursive construction of femininity and sexuality shapes the way women construct and experience their illness and their body - leading many women to try to appear 'normal' to others post-breast surgery. Finally, the quality of a woman's partnered relationship consistently predicts sexual health post-breast cancer - reinforcing the importance of recognising the intersubjective nature of issues surrounding breast cancer and sexuality. It is concluded that analyses of sexuality in the context of breast cancer cannot conceptualise the physical body separately from women's intrapsychic negotiation, her social and relational context, and the discursive constructions of sexuality and femininity: a material-discursive-intrapsychic interaction.

  17. Sexuality after breast cancer: a review.

    PubMed

    Gilbert, Emilee; Emilee, Gilbert; Ussher, J M; Perz, J

    2010-08-01

    It is widely recognised that women's sexuality can be particularly complex after breast cancer, with sexual changes often becoming the most problematic aspect of a woman's life. The impact of such changes can last for many years after successful treatment, and can be associated with serious physical and emotional side-effects. The objective of this paper is to review research on breast cancer and sexuality from the years 1998 to 2010. Research has documented a range of physical changes to a woman's sexuality following breast cancer, including disturbances to sexual functioning, as well as disruptions to sexual arousal, lubrication, orgasm, sexual desire, and sexual pleasure, resulting from chemotherapy, chemically induced menopause, tamoxifen, and breast cancer surgery. Women's intrapsychic experience of changes to sexuality includes a fear of loss of fertility, negative body image, feelings of sexual unattractiveness, loss of femininity, depression and anxiety, as well as alterations to a sense of sexual self. The discursive construction of femininity and sexuality shapes the way women construct and experience their illness and their body - leading many women to try to appear 'normal' to others post-breast surgery. Finally, the quality of a woman's partnered relationship consistently predicts sexual health post-breast cancer - reinforcing the importance of recognising the intersubjective nature of issues surrounding breast cancer and sexuality. It is concluded that analyses of sexuality in the context of breast cancer cannot conceptualise the physical body separately from women's intrapsychic negotiation, her social and relational context, and the discursive constructions of sexuality and femininity: a material-discursive-intrapsychic interaction. PMID:20439140

  18. Breast-feeding and benign breast disease.

    PubMed

    Bernardi, S; Londero, A P; Bertozzi, S; Driul, L; Marchesoni, D; Petri, R

    2012-01-01

    Benign breast disease (BBD) is very common among women in their fertile age, but its correlation with breast reproductive function remains unclear. Our study aimed to investigate the relation between BBD and breast-feeding. We collected data on 105 women with BBD and 98 controls, focusing on their reproductive history and breast-feeding. We analysed data by R (version 2.12.1) considering p < 0.05 as significant. The results showed that fibroadenoma represented the most frequent BBD (55%), followed by fibrocystic changes (19%), intraductal papilloma (6%) and inflammatory breast disorders (5%). The mean age was 31.5 years (± 6.1), BMI 21.2 kg/m² (± 3.4) and age at menarche 13.0 years (± 1.5). Duration of breast-feeding was not significantly different between controls and BBD types (p = NS). Selecting women with fibroadenoma breast-feeding duration directly correlated with the number of benign lesions (p < 0.05), which remains significant also by multivariate analysis. It was concluded that there seemed to be no difference in breast-feeding among BBDs types, but lactation may influence the number of fibroadenomas. Moreover, prospective studies would better define the correlation between lactation and BBDs.

  19. The aging prostate is never "normal": implications from the genomic characterization of multifocal prostate cancers.

    PubMed

    Schlomm, Thorsten; Weischenfeldt, Joachim; Korbel, Jan; Sauter, Guido

    2015-09-01

    We argue against the recently published statement that tumor-specific molecular alterations found in "normal" prostate tissue from cancer patients challenge focal therapy approaches that only target a visible cancer lesion and not the adjacent molecular field.

  20. Human mammaglobin in breast cancer: a brief review of its clinical utility

    PubMed Central

    Al Joudi, Fawwaz Shakir

    2014-01-01

    Human mammaglobin is a member of the uteroglobin proteins family that has recently been tested as a specific marker for breast cancer. While low levels may be seen in normal breast tissue, expression is increased dramatically in breast cancer and is correlated with higher grade. Detection in blood and body fluids is also correlated with cancer metastasis, and its levels with prognosis. This promises to be a useful screen for early detection of breast cancer, especially in high risk individuals. Mammoglobin has also been used for immunotherapeutic targeting of breast cancer cells. However, there are some controversies regarding its diagnostic efficacy and prognostic value, which warrant further study. PMID:25027076

  1. Minireview: The Androgen Receptor in Breast Tissues: Growth Inhibitor, Tumor Suppressor, Oncogene?

    PubMed Central

    Hickey, T. E.; Robinson, J. L. L.; Carroll, J. S.

    2012-01-01

    Androgen receptor (AR) signaling exerts an antiestrogenic, growth-inhibitory influence in normal breast tissue, and this role may be sustained in estrogen receptor α (ERα)-positive luminal breast cancers. Conversely, AR signaling may promote growth of a subset of ERα-negative, AR-positive breast cancers with a molecular apocrine phenotype. Understanding the molecular mechanisms whereby androgens can elicit distinct gene expression programs and opposing proliferative responses in these two breast cancer phenotypes is critical to the development of new therapeutic strategies to target the AR in breast cancer. PMID:22745190

  2. 4. Elevation looking southwest from adjacent hills on northeast side ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. Elevation looking southwest from adjacent hills on northeast side of bridge, taken from river level. Note entire east side and substructure. - Presumpscot Falls Bridge, Spanning Presumptscot River at Allen Avenue extension, 0.75 mile west of U.S. Interstate 95, Falmouth, Cumberland County, ME

  3. 12. VIEW LOOKING WEST FROM THE PARKING LOT ADJACENT TO ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. VIEW LOOKING WEST FROM THE PARKING LOT ADJACENT TO THE STEEL PLANT OFFICES. BAR AND BILLET MILLS AND, IN THE DISTANCE, THE BASIC OXYGEN FURNACES MAY BE SEEN. - Corrigan, McKinney Steel Company, 3100 East Forty-fifth Street, Cleveland, Cuyahoga County, OH

  4. 8. Exterior view, showing tank and associated piping adjacent to ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. Exterior view, showing tank and associated piping adjacent to Test Cell 6, Systems Integration Laboratory Building (T-28), looking south. - Air Force Plant PJKS, Systems Integration Laboratory, Systems Integration Laboratory Building, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

  5. 10. Detail and contextual view of bridge and adjacent farmstead ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. Detail and contextual view of bridge and adjacent farmstead setting. Note laced vertical compression members, latticed portal strut, decorative strut bracing, and lightness of diagonal and lateral tension members. View to southeast through southeast portal from truss mid-span. - Red Bank Creek Bridge, Spanning Red Bank Creek at Rawson Road, Red Bluff, Tehama County, CA

  6. 11. Interior detail, Boiler Room, fire door to the adjacent ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    11. Interior detail, Boiler Room, fire door to the adjacent Blacksmith Shop, Roundhouse Machine Shop Extension, Southern Pacific Railroad Carlin Shops, view to southwest (90mm lens). - Southern Pacific Railroad, Carlin Shops, Roundhouse Machine Shop Extension, Foot of Sixth Street, Carlin, Elko County, NV

  7. 1. VIEW FROM SOUTHWEST SHOWING SOUTH (FRONT) ELEVATION, ADJACENT LOUGHRAN ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. VIEW FROM SOUTHWEST SHOWING SOUTH (FRONT) ELEVATION, ADJACENT LOUGHRAN BUILDING (BASSIN'S RESTAURANT) (HABS No. DC-357), 501-511 14TH STREET (THE LOCKER ROOM) HABS No. DC-356) ON CORNER, AND MUNSEY BUILDING (HABS No. DC-358) - William J. Stone Building, 1345 E Street Northwest, Washington, District of Columbia, DC

  8. VIEW FROM ATOP ADJACENT RESIDENTIAL TOWER, SHOWING RECREATION AREA AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW FROM ATOP ADJACENT RESIDENTIAL TOWER, SHOWING RECREATION AREA AND ENTRY TO NEIGHBORHOOD. VIEW FACING SOUTHEAST - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Intersection of Acacia Road and Brich Circle, Pearl City, Honolulu County, HI

  9. VIEW FROM ATOP ADJACENT RESIDENTIAL TOWER, SHOWING INTERSECTION OF ACACIA ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW FROM ATOP ADJACENT RESIDENTIAL TOWER, SHOWING INTERSECTION OF ACACIA ROAD WITH BIRCH CIRCLE. VIEW FACING NORTHEAST - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Intersection of Acacia Road and Brich Circle, Pearl City, Honolulu County, HI

  10. VIEW FROM ATOP ADJACENT RESIDENTIAL TOWER, SHOWING RECREATION AREA ON ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW FROM ATOP ADJACENT RESIDENTIAL TOWER, SHOWING RECREATION AREA ON RIGHT, AND HOUSING AREA ON LEFT. VIEW FACING EAST/NORTHEAST - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Intersection of Acacia Road and Brich Circle, Pearl City, Honolulu County, HI

  11. VIEW FROM ATOP ADJACENT RESIDENTIAL TOWER, SHOWING WESTERN SIDE OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW FROM ATOP ADJACENT RESIDENTIAL TOWER, SHOWING WESTERN SIDE OF NEIGHBORHOOD. VIEW FACING NORTHWEST - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Intersection of Acacia Road and Brich Circle, Pearl City, Honolulu County, HI

  12. 1. OVERVIEW SHOWING FIRING CONTROL BLOCKHOUSE 0502 AND ADJACENT OBSERVATION ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. OVERVIEW SHOWING FIRING CONTROL BLOCKHOUSE 0502 AND ADJACENT OBSERVATION TOWER. WATER BRAKE TROUGH SEGMENT AT LOWER RIGHT. Looking north northeast. - Edwards Air Force Base, South Base Sled Track, Firing & Control Blockhouse for 10,000-foot Track, South of Sled Track at midpoint of 20,000-foot track, Lancaster, Los Angeles County, CA

  13. 22. Float located adjacent to entry stair in filtration bed. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    22. Float located adjacent to entry stair in filtration bed. The float actuates a valve that maintains water level over the bed. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  14. 7. VIEW OF WATER TREATMENT PLANT, ADJACENT TO THE COAL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. VIEW OF WATER TREATMENT PLANT, ADJACENT TO THE COAL CONVEYOR; IN THE DISTANCE IS THE FREQUENCY CHANGER HOUSE, WHICH IS ATTACHED TO SWITCH HOUSE NO. 1; LOOKING WEST. - Commonwealth Electric Company, Fisk Street Electrical Generating Station, 1111 West Cermak Avenue, Chicago, Cook County, IL

  15. 4. REAR ELEVATION, DETAIL OF CONSTRUCTION, ADJACENT CORNER POSTS BETWEEN ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. REAR ELEVATION, DETAIL OF CONSTRUCTION, ADJACENT CORNER POSTS BETWEEN BUILDING PERIODS 1 AND 3. NOTE REUSED WOOD STRIP NAILED TO BUILDING PERIOD 1 POST INSCRIBED 'ST. LEONARD'. THERE ARE NO NAIL HOLES IN THE PERIOD 3 POST, THE FARRING STRIPS ADJUST FOR CLADDING - Charles' Gift, State Routes 2 & 4, Lusby, Calvert County, MD

  16. Biogeochemistry of hydrothermally and adjacent non-altered soils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    As a field/lab project, students in the Soil Biogeochemistry class of the University of Nevada, Reno described and characterized seven pedons, developed in hydrothermally and adjacent non-hydrothermally altered andesitic parent material near Reno, NV. Hydrothermally altered soils had considerably lo...

  17. 12. LOG FOUNDATION ELEMENTS OF THE SAWMILL ADJACENT TO THE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. LOG FOUNDATION ELEMENTS OF THE SAWMILL ADJACENT TO THE CANAL, LOOKING EAST. BARREN AREA IN FOREGROUND IS DECOMPOSING SAWDUST. DIRT PILE IN BACKGROUND IS THE EDGE OF THE SUMMIT COUNTY LANDFILL. - Snake River Ditch, Headgate on north bank of Snake River, Dillon, Summit County, CO

  18. LEHR NO. 2 AND LEHR NO. 3 ADJACENT TO FURNACE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    LEHR NO. 2 AND LEHR NO. 3 ADJACENT TO FURNACE ROOM; THE PIPES AT THE BOTTOM ARE PART OF THE RADIANT HEATING SYSTEM USED FOR HEATING THE FACTORY DURING COLD WEATHER. - Westmoreland Glass Company, Seventh & Kier Streets, Grapeville, Westmoreland County, PA

  19. How subaerial salt extrusions influence water quality in adjacent aquifers

    NASA Astrophysics Data System (ADS)

    Mehdizadeh, Razieh; Zarei, Mehdi; Raeisi, Ezzat

    2015-12-01

    Brines supplied from salt extrusions cause significant groundwater salinization in arid and semi-arid regions where salt rock is exposed to dissolution by episodic rainfalls. Here we focus on 62 of the 122 diapirs of Hormuz salt emergent in the southern Iran. To consider managing the degradation effect that salt extrusions have on the quality of adjoining aquifers, it is first necessary to understand how they influence adjacent water resources. We evaluate here the impacts that these diapirs have on adjacent aquifers based on investigating their geomorphologies, geologies, hydrologies and hydrogeologies. The results indicate that 28/62 (45%) of our sample of salt diapirs have no significant impact on the quality of groundwater in adjoining aquifers (namely Type N), while the remaining 34/62 (55%) degrade nearby groundwater quality. We offer simple conceptual models that account for how brines flowing from each of these types of salt extrusions contaminate adjacent aquifers. We identify three main mechanisms that lead to contamination: surface impact (Type A), subsurface intrusion (Type B) and indirect infiltration (Type C). A combination of all these mechanisms degrades the water quality in nearby aquifers in 19/62 (31%) of the salt diapirs studied. Having characterized the mechanism(s) by which each diapir affects the adjacent aquifer, we suggest a few possible remediation strategies to be considered. For instance, engineering the surface runoff of diapirs Types A and C into nearby evaporation basins would improve groundwater quality.

  20. Breast cancer detection in rotational thermography images using texture features

    NASA Astrophysics Data System (ADS)

    Francis, Sheeja V.; Sasikala, M.; Bhavani Bharathi, G.; Jaipurkar, Sandeep D.

    2014-11-01

    Breast cancer is a major cause of mortality in young women in the developing countries. Early diagnosis is the key to improve survival rate in cancer patients. Breast thermography is a diagnostic procedure that non-invasively images the infrared emissions from breast surface to aid in the early detection of breast cancer. Due to limitations in imaging protocol, abnormality detection by conventional breast thermography, is often a challenging task. Rotational thermography is a novel technique developed in order to overcome the limitations of conventional breast thermography. This paper evaluates this technique's potential for automatic detection of breast abnormality, from the perspective of cold challenge. Texture features are extracted in the spatial domain, from rotational thermogram series, prior to and post the application of cold challenge. These features are fed to a support vector machine for automatic classification of normal and malignant breasts, resulting in a classification accuracy of 83.3%. Feature reduction has been performed by principal component analysis. As a novel attempt, the ability of this technique to locate the abnormality has been studied. The results of the study indicate that rotational thermography holds great potential as a screening tool for breast cancer detection.

  1. Nerve Fibers in Breast Cancer Tissues Indicate Aggressive Tumor Progression

    PubMed Central

    Huang, Di; Su, Shicheng; Cui, Xiuying; Shen, Ximing; Zeng, Yunjie; Wu, Wei; Chen, Jianing; Chen, Fei; He, Chonghua; Liu, Jiang; Huang, Wei; Liu, Qiang; Su, Fengxi; Song, Erwei; Ouyang, Nengtai

    2014-01-01

    Abstract Emerging evidence has indicated nerve fibers as a marker in the progression of various types of cancers, such as pancreatic cancer and prostate cancer. However, whether nerve fibers are associated with breast cancer progression remains unclear. In this study, we evaluated the presence of nerve fibers in 352 breast cancer specimens and 83 benign breast tissue specimens including 43 cases of cystic fibrosis and 40 cases of fibroadenoma from 2 independent breast tumor center using immunohistochemical staining for specific peripheral nerve fiber markers. In all, nerve fibers were present in 130 out of 352 breast cancer tissue specimens, while none were detected in normal breast tissue specimens. Among 352 cases, we defined 239 cases from Sun Yat-Sen Memorial Hospital, Guangzhou, China, as the training set, and 113 cases from the First Affiliated Hospital of Shantou University, Guangdong, China, as the validation set. The thickness of tumor-involving nerve fibers is significantly correlated with poor differentiation, lymph node metastasis, high clinical staging, and triple negative subtype in breast cancer. More importantly, Cox multifactor analysis indicates that the thickness of tumor-involving nerve fibers is a previously unappreciated independent prognostic factors associated with shorter disease-free survival of breast cancer patients. Our findings are further validated by online Oncomine database. In conclusion, our results show that nerve fiber involvement in breast cancer is associated with progression of the malignancy and warrant further studies in the future. PMID:25501061

  2. Identification of Novel Tumor Markers in Prostate, Colon and Breast Cancer by Unbiased Methylation Profiling

    PubMed Central

    Chung, Woonbok; Kwabi-Addo, Bernard; Ittmann, Michael; Jelinek, Jaroslav; Shen, Lanlan; Yu, Yinhua; Issa, Jean-Pierre J.

    2008-01-01

    DNA hypermethylation is a common epigenetic abnormality in cancer and may serve as a useful marker to clone cancer-related genes as well as a marker of clinical disease activity. To identify CpG islands methylated in prostate cancer, we used methylated CpG island amplification (MCA) coupled with representational difference analysis (RDA) on prostate cancer cell lines. We isolated 34 clones that corresponded to promoter CpG islands, including 5 reported targets of hypermethylation in cancer. We confirmed the data for 17 CpG islands by COBRA and/or pyrosequencing. All 17 genes were methylated in at least 2 cell lines of a 21-cancer cell line panel containing prostate cancer, colon cancer, leukemia, and breast cancer. Based on methylation in primary tumors compared to normal adjacent tissues, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS and NSE1 are candidate biomarkers for prostate cancer (methylation range 50%–85%). The combination of NSE1 or SPOCK2 hypermethylation showed a sensitivity of 80% and specificity of 95% in differentiating cancer from normal. Similarly NKX2-5, SPOCK2, SLC16A12, DPYS and GALR2 are candidate biomarkers for colon cancer (methylation range 60%–95%) and GALR2 hypermethylation showed a sensitivity of 85% and specificity of 95%. Finally, SLC16A12, GALR2, TOX, SPOCK2, EGFR5 and DPYS are candidate biomarkers for breast cancer (methylation range 33%–79%) with the combination of EGFR5 or TOX hypermethylation showing a sensitivity of 92% and specificity of 92%. Expression analysis for eight genes that had the most hypermethylation confirmed the methylation associated silencing and reactivation with 5-aza-2′-deoxycytidine treatment. Our data identify new targets of transcriptional silencing in cancer, and provide new biomarkers that could be useful in screening for prostate cancer and other cancers. PMID:18446232

  3. 31. DETAIL: A view of the south breast wall of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    31. DETAIL: A view of the south breast wall of the west lock gate. A prototypical crib is shown immediately behind the wall in the center of the photograph and includes the first rear wall, with rough timbers, and ties within the crib. Some remaining stone ballast is also visible, wedged between the ties. - Wabash & Erie Canal, Lock No. 2, 8 miles east of Fort Wayne, adjacent to U.S. Route 24, New Haven, Allen County, IN

  4. Optical biopsy of breast cancer tissue

    NASA Astrophysics Data System (ADS)

    AlSalhi, M. S.; Ben Amer, S.; Farhat, K.; Rabah, D.; Devanesan, S.; Atif, M.; Masilamani, V.; Al-Dakheel, Reem. K. S.

    2012-08-01

    In this paper, we report results of Fluorescence Emission Spectra (FES) and Stokes Shift Spectra (SSS) of 19 cancer tissue of invasive ductal carcinoma of different grades in comparison with normal breast tissues (obtained away from tumor regions). We were able to get distinct differences in the spectral features of normal and malignant tissues in terms of the ratios of concentrations of biomolecules like tryptophan, collagen and NADH. The sensitivity and specificity were in the range of 75%. What was all the more important was the parallelism in the spectral features of normal and malignant breast tissue pieces of above set of subjects. The objective of our research is to evolve one such protocol and the first step is the spectral characterization of in vitro optical analyses of excised tumor tissues.

  5. Imaging Guided Breast Interventions.

    PubMed

    Masroor, Imrana; Afzal, Shaista; Sufian, Saira Naz

    2016-06-01

    Breast imaging is a developing field, with new and upcoming innovations, decreasing the morbidity and mortality related to breast pathologies with main emphasis on breast cancer. Breast imaging has an essential role in the detection and management of breast disease. It includes a multimodality approach, i.e. mammography, ultrasound, magnetic resonance imaging, nuclear medicine techniques and interventional procedures, done for the diagnosis and definitive management of breast abnormalities. The range of methods to perform biopsy of a suspicious breast lesion found on imaging has also increased markedly from the 1990s with hi-technological progress in surgical as well as percutaneous breast biopsy methods. The image guided percutaneous breast biopsy procedures cause minimal breast scarring, save time, and relieve the patient of the anxiety of going to the operation theatre. The aim of this review was to describe and discuss the different image guided breast biopsy techniques presently employed along with the indications, contraindication, merits and demerits of each method. PMID:27353993

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

    ClinicalTrials.gov

    2011-12-07

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

  7. Docosahexaenoic Acid in Preventing Recurrence in Breast Cancer Survivors

    ClinicalTrials.gov

    2016-06-20

    Benign Breast Neoplasm; Ductal Breast Carcinoma In Situ; Invasive Breast Carcinoma; Lobular Breast Carcinoma In Situ; Paget Disease of the Breast; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  8. Missense mutations (p.H371Y, p.D438Y) in gene CHEK2 are associated with breast cancer risk in women of Balochistan origin.

    PubMed

    Baloch, Abdul Hameed; Daud, Shakeela; Raheem, Nafeesa; Luqman, Muhammad; Ahmad, Adeel; Rehman, Abdul; Shuja, Jameela; Rasheed, Saeeda; Ali, Akhtar; Kakar, Naseebullah; Naseeb, Hafiz Khush; Mengal, Mohammad Alam; Awan, Muhammad Arif; Wasim, Muhammad; Baloch, Dost Mohammad; Ahmad, Jamil

    2014-02-01

    CHEK2 encodes a serine/threonine-protein kinase which plays a critical role in DNA damage signaling pathways. CHEK2 directly phosphorylates and regulates the functions of p53 and BRCA1. Most women with breast and/or ovarian cancer are not carriers of mutant BRCA1 or BRCA2. Multiple studies have shown that a CHEK2*1100delC confers about a two-fold increased risk of breast cancer in unselected females and a tenfold increase in males. Moreover, studies have shown that first-degree relatives of bilateral breast cancer cases who carried the CHEK2*1100delC allele had an eight-fold increased risk of breast cancer. It has been suggested that CHEK2 functions as a low-penetrance susceptibility gene for cancers and multiplies the risks associated with other gene(s) to increase cancer risk. The main goal of this study was to evaluate and to compare the role of truncating mutations, splice junction mutations and rare missense substitutions in breast cancer susceptibility gene CHEK2. Present study was performed on 140 individuals including 70 breast cancer patients both with and without family history and 70 normal individuals. Written consent was obtained and 3 ml intravenous blood was drawn from all the subjects. DNA was extracted from all the samples through inorganic method published already. Primers were synthesized for all the 14 exons of CHEK2 gene. Coding and adjacent intronic sequences of CHEK2 gene were amplified and sequenced. Two genetic variants (p.H371Y, p.D438Y) were found in exon 10 and exon 11 of gene CHEK2 which were not found in any of the 70 control individuals from same geographical area and ethnic group. The genetic variant c.1312G>T (p.D438Y) identified in a patient with a family history of breast cancer. To our knowledge, this is first mutation scanning study of gene CHEK2 from Balochistan population.

  9. FOXO factors and breast cancer: outfoxing endocrine resistance.

    PubMed

    Bullock, M

    2016-02-01

    The majority of metastatic breast cancers cannot be cured and present a major public health problem worldwide. Approximately 70% of breast cancers express the estrogen receptor, and endocrine-based therapies have significantly improved patient outcomes. However, the development of endocrine resistance is extremely common. Understanding the molecular pathways that regulate the hormone sensitivity of breast cancer cells is important to improving the efficacy of endocrine therapy. It is becoming clearer that the PI3K-AKT-forkhead box O (FOXO) signaling axis is a key player in the hormone-independent growth of many breast cancers. Constitutive PI3K-AKT pathway activation, a driver of breast cancer growth, causes down-regulation of FOXO tumor suppressor functions. This review will summarize what is currently known about the role of FOXOs in endocrine-resistance mechanisms. It will also suggest potential therapeutic strategies for the restoration of normal FOXO transcriptional activity.

  10. The hallmarks of breast cancer by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Abramczyk, H.; Surmacki, J.; Brożek-Płuska, B.; Morawiec, Z.; Tazbir, M.

    2009-04-01

    This paper presents new biological results on ex vivo breast tissue based on Raman spectroscopy and demonstrates its power as diagnostic tool with the key advantage in breast cancer research. The results presented here demonstrate the ability of Raman spectroscopy to accurately characterize cancer tissue and distinguish between normal, malignant and benign types. The goal of the paper is to develop the diagnostic ability of Raman spectroscopy in order to find an optical marker of cancer in the breast tissue. Applications of Raman spectroscopy in breast cancer research are in the early stages of development in the world. To the best of our knowledge, this paper is one of the most statistically reliable reports (1100 spectra, 99 patients) on Raman spectroscopy-based diagnosis of breast cancers among the world women population.

  11. Neuropeptide Y Y1 receptors meditate targeted delivery of anticancer drug with encapsulated nanoparticles to breast cancer cells with high selectivity and its potential for breast cancer therapy.

    PubMed

    Li, Juan; Shen, Zheyu; Ma, Xuehua; Ren, Wenzhi; Xiang, Lingchao; Gong, An; Xia, Tian; Guo, Junming; Wu, Aiguo

    2015-03-11

    By enabling nanoparticle-based drug delivery system to actively target cancer cells with high selectivity, active targeted molecules have attracted great attention in the application of nanoparticles for anticancer drug delivery. However, the clinical application of most active targeted molecules in breast cancer therapy is limited, due to the low expression of their receptors in breast tumors or coexpression in the normal and tumor breast tissues. Here, a neuropeptide Y Y1 receptors ligand PNBL-NPY, as a novel targeted molecule, is conjugated with anticancer drug doxorubicin encapsulating albumin nanoparticles to investigate the effect of Y1 receptors on the delivery of drug-loaded nanoparticles to breast cancer cells and its potential for breast cancer therapy. The PNBL-NPY can actively recognize and bind to the Y1 receptors that are significantly overexpressed on the surface of the breast cancer cells, and the drug-loaded nanoparticles are delivered directly into the cancer cells through internalization. This system is highly selective and able to distinguish the breast cancer cells from the normal cells, due to normal breast cells that express Y2 receptors only. It is anticipated that this study may provide a guidance in the development of Y1 receptor-based nanoparticulate drug delivery system for a safer and more efficient breast cancer therapy.

  12. Do fatty breasts increase or decrease breast cancer risk?

    PubMed Central

    2012-01-01

    Few studies have investigated the association of non-dense area or fatty breasts in conjunction with breast density and breast cancer risk. Two articles in a recent issue of Breast Cancer Research investigate the role of absolute non-dense breast area measured on mammograms and find conflicting results: one article finds that non-dense breast area has a modest positive association with breast cancer risk, whereas the other finds that non-dense breast area has a strong protective effect to reduce breast cancer risk. Understanding the interplay of body mass index, menopause status, and measurement of non-dense breast area would help to clarify the contribution of non-dense breast area to breast cancer risk. PMID:22277587

  13. Targeting Notch degradation system provides promise for breast cancer therapeutics.

    PubMed

    Liu, Jing; Shen, Jia-Xin; Wen, Xiao-Fen; Guo, Yu-Xian; Zhang, Guo-Jun

    2016-08-01

    Notch receptor signaling pathways play an important role, not only in normal breast development but also in breast cancer development and progression. As a group of ligand-induced proteins, different subtypes of mammalian Notch (Notch1-4) are sensitive to subtle changes in protein levels. Thus, a clear understanding of mechanisms of Notch protein turnover is essential for understanding normal and pathological mechanisms of Notch functions. It has been suggested that there is a close relationship between the carcinogenesis and the dysregulation of Notch degradation. However, this relationship remains mostly undefined in the context of breast cancer, as protein degradation is mediated by numerous signaling pathways as well as certain molecule modulators (activators/inhibitors). In this review, we summarize the published data regarding the regulation of Notch family member degradation in breast cancer, while emphasizing areas that are likely to provide new therapeutic modalities for mechanism-based anti-cancer drugs.

  14. Development of three-dimensional radiotherapy techniques in breast cancer

    NASA Astrophysics Data System (ADS)

    Coles, Charlotte E.

    Radiotherapy following conservation surgery decreases local relapse and death from breast cancer. Currently, the challenge is to minimise the morbidity caused by this treatment without losing efficacy. Despite many advances in radiation techniques in other sites of the body, the majority of breast cancer patients are still planned and treated using 2-dimensional simple radiotherapy techniques. In addition, breast irradiation currently consumes 30% of the UK's radiotherapy workload. Therefore, any change to more complex treatment should be of proven benefit. The primary objective of this research is to develop and evaluate novel radiotherapy techniques to decrease irradiation of normal structures and improve localisation of the tumour bed. I have developed a forward-planned intensity modulated (IMRT) breast radiotherapy technique, which has shown improved dosimetry results compared to standard breast radiotherapy. Subsequently, I have developed and implemented a phase III randomised controlled breast IMRT trial. This National Cancer Research Network adopted trial will answer an important question regarding the clinical benefit of breast IMRT. It will provide DNA samples linked with high quality clinical outcome data, for a national translational radiogenomics study investigating variation in normal tissue toxicity. Thus, patients with significant late normal tissue side effects despite good dose homogeneity will provide the best model for finding differences due to underlying genetics. I evaluated a novel technique using high definition free-hand 3-dimensional (3D) ultrasound in a phantom study, and the results suggested that this is an accurate and reproducible method for tumour bed localisation. I then compared recognised methods of tumour bed localisation with the 3D ultrasound method in a clinical study. The 3D ultrasound technique appeared to accurately represent the shape and spatial position of the tumour cavity. This tumour bed localisation research

  15. New adjacent Bis-tetrahydrofuran Annonaceous acetogenins from Annona muricata.

    PubMed

    Chang, Fang-Rong; Liaw, Chih-Chuang; Lin, Chih-Yuan; Chou, Chi-Jung; Chiu, Hui-Fen; Wu, Yang-Chang

    2003-03-01

    Bioactivity-guided fractionation led to the isolation of two new Annonaceous acetogenins, annocatacin A ( 1). and annocatacin B ( 2). from the seeds and the leaves, respectively, of Annona muricata. Compounds 1 and 2 are the first examples where the adjacent bis-tetrahydrofuran ring system is located at C-15. The new structures were elucidated and characterized by spectral and chemical methods. Both Annonaceous acetogenins 1 and 2 showed significant in vitro cytotoxicity toward the human hepatoma cell lines, Hep G2 and 2,2,15, and were compared with the known adjacent bis-tetrahydrofuran acetogenins, neoannonin ( 3). desacetyluvaricin ( 4). bullatacin ( 5). asimicin ( 6). annoglaucin ( 7). squamocin ( 8). and rollimusin ( 9).

  16. Living as a Breast Cancer Survivor

    MedlinePlus

    ... Emotional aspects of breast cancer Living as a breast cancer survivor For many women with breast cancer, treatment ... making some new choices. Follow-up care after breast cancer treatment Even after you have completed breast cancer ...

  17. Breast Cancer Risk in American Women

    MedlinePlus

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

  18. 38. VIEW OF COTTRELL MAGNETIC IMPULSE GENERATOR ADJACENT TO SIX ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    38. VIEW OF COTTRELL MAGNETIC IMPULSE GENERATOR ADJACENT TO SIX GAP ROTARY RECTIFIER. THIS UNIT GENERATED A MAGNETIC PULSE WHICH WAS TRANSMITTED TO THE COLLECTION PLATES IN THE ELECTROSTATIC PRECIPITATOR CHAMBER. THESE PERIODIC PULSES VIBRATE THE PLATES AND CAUSE PRECIPITATED ARTICLES OF SMOKE AND FLY ASH TO FALL TO THE BOTTOM OF THE PRECIPITATOR CHAMBER. - New York, New Haven & Hartford Railroad, Cos Cob Power Plant, Sound Shore Drive, Greenwich, Fairfield County, CT

  19. 20. Interior view of fuel storage pit or vault adjacent ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. Interior view of fuel storage pit or vault adjacent to Test Cell 9 in Component Test Laboratory (T-27), looking west. Photograph shows upgraded instrumentation, piping, tanks, and technological modifications installed in 1997-99 to accommodate component testing requirements for the Atlas V missile. - Air Force Plant PJKS, Systems Integration Laboratory, Components Test Laboratory, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

  20. Osmium complex binding to mismatched methylcytosine: effect of adjacent bases.

    PubMed

    Nomura, Akiko; Tainaka, Kazuki; Okamoto, Akimitsu

    2009-01-01

    We investigated the efficiency of osmium complex formation at 5-methylcytosine in mismatched DNA duplexes. Osmium complexation was not observed in fully matched duplexes, whereas the complexation site and efficiency in mismatched duplexes depended on the 5'-neighboring base of the 5-methylcytosine. In particular, when the base adjacent to the 5' side of the mismatched base pair was thymine, a unique side reaction was observed. However, the mismatched base pairs did not influence the selectivity of osmium complexation with methylated DNA.

  1. Conference room 211, adjacent to commander's quarters, with vault door ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Conference room 211, adjacent to commander's quarters, with vault door at right. Projection area at center is equipped with automatic security drapes. Projection room uses a 45 degree mirror to reflect the image onto the frosted glass screen. Door on far left leads to display area senior battle staff viewing bridge, and the commander's quarters - March Air Force Base, Strategic Air Command, Combat Operations Center, 5220 Riverside Drive, Moreno Valley, Riverside County, CA

  2. Mutual Diffusional Interference Between Adjacent Stomata of a Leaf 1

    PubMed Central

    Cook, G. D.; Viskanta, R.

    1968-01-01

    The mutual diffusional interference between adjacent stomata in laminar flow over a leaf is shown to play a decisive role in determining overall transpiration. The magnitude of this interference varies with the interaction of the vapor diffusional shells forming above each stoma and the air flow over the leaf. The interference decreases with increasing incident radiation and wind velocity. The effect of interference on the stomatal resistance to diffusion plays a major role in the overall variations in transpiration. PMID:16656876

  3. Fouling assemblages on offshore wind power plants and adjacent substrata

    NASA Astrophysics Data System (ADS)

    Wilhelmsson, Dan; Malm, Torleif

    2008-09-01

    A significant expansion of offshore wind power is expected in the near future, with thousands of turbines in coastal waters, and various aspects of how this may influence the coastal ecology including disturbance effects from noise, shadows, electromagnetic fields, and changed hydrological conditions are accordingly of concern. Further, wind power plants constitute habitats for a number of organisms, and may locally alter assemblage composition and biomass of invertebrates, algae and fish. In this study, fouling assemblages on offshore wind turbines were compared to adjacent hard substrate. Influences of the structures on the seabed were also investigated. The turbines differed significantly from adjacent boulders in terms of assemblage composition of epibiota and motile invertebrates. Species number and Shannon-Wiener diversity were, also, significantly lower on the wind power plants. It was also indicated that the turbines might have affected assemblages of invertebrates and algae on adjacent boulders. Off shore wind power plant offer atypical substrates for fouling assemblages in terms of orientation, depth range, structure, and surface texture. Some potential ecological implications of the addition of these non-natural habitats for coastal ecology are discussed.

  4. Breast Cancer Rates by State

    MedlinePlus

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

  5. CDC Vital Signs: Breast Cancer

    MedlinePlus

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

  6. Genetics Home Reference: breast cancer

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions breast cancer breast cancer Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Breast cancer is a disease in which certain cells in ...

  7. 6 Common Cancers - Breast Cancer

    MedlinePlus

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

  8. Expected resolution and detectability of adenocarcinoma tumors within human breast in time-resolved images

    NASA Astrophysics Data System (ADS)

    Gandjbakhche, Amir H.; Nossal, Ralph J.; Dadmarz, Roya; Schwartzentruber, Douglas; Bonner, Robert F.

    1995-04-01

    The prospects for time-resolved optical mammography rests on the ability to detect adenocarcinoma within the breast with sufficient resolution and specificity to compete with X-ray mammography. We characterized the optical properties of an unusually large (6 cm diameter) fresh adenocarcinoma and normal breast tissue (determined by histology to be predominantly adipose tissue) obtained from a patient undergoing mastectomy. Large specimens (5 mm thick and 3 cm wide) allowed the determination of absorption and scattering coefficients and their spatial heterogeneity as probed with a 1 mm diameter laser beam at 633 nm and 800 nm utilizing total reflectance and transmittance measure with integrating spheres. The difference between scattering coefficients of the malignant tumor and those of normal (principally adipose) breast tissue at 633 nm was much greater than the heterogeneity within each sample. This scattering difference is the principal source of contrast, particularly in time-resolved images. However, the high scattering coefficient of normal breast tissue at 633 nm limits the practicality of time-resolved mammography of a human breast compressed to 5 cm. Although the scattering coefficient of the normal breast tissue decreases at 800 nm, the differences between the optical properties of normal and abnormal breast tissue also are reduced. We used these empirical results in theoretical expressions obtained from random walk theory to quantify the expected resolution, contrast, and the detected intensity of 3, 6, and 9 mm tumors within otherwise homogeneous human breasts as a function of the gating-time of time-resolved optical mammography.

  9. Obesity and its impact on breast cancer: tumor incidence, recurrence, survival, and possible interventions.

    PubMed

    Ligibel, Jennifer A; Strickler, Howard D

    2013-01-01

    A positive association between obesity and the risk of incident postmenopausal breast cancer has been consistently observed in epidemiologic studies. Although most studies of premenopausal women have not found a similar relationship between breast cancer and obesity, the prognosis for both pre- and postmenopausal breast cancer is substantially worse among obese than normal-weight individuals. Increasing evidence suggests that these associations may be mechanistically related to sex hormones, insulin, and certain adipokines. Insulin, for example, has important mitogenic/antiapoptotic activity in addition to its metabolic effects, and many breast tumors express high levels of the insulin receptor (IR)-A isoform. Further, the use of metformin, a diabetes medication that reduces insulin levels, has been epidemiologically associated with reduced breast cancer risk among patients with diabetes, and a recent observational study found a higher rate of pathologic complete responses among patients with diabetes and breast cancer who were using metformin. Formal clinical trials of metformin as adjuvant breast cancer therapy have been initiated and are ongoing. Similarly, the effect of lifestyle changes on breast cancer outcomes is actively being investigated. Several lifestyle intervention studies have demonstrated that weight loss, increased physical activity, and dietary changes are feasible in breast cancer populations, and that individuals who make lifestyle changes after breast cancer diagnosis experience several physical and psychologic benefits. In this article, the authors review the evidence linking obesity with breast cancer risk and outcomes and provide an overview of lifestyle intervention studies in patients with breast cancer.

  10. Portraying breast cancers with long noncoding RNAs

    PubMed Central

    Van Grembergen, Olivier; Bizet, Martin; de Bony, Eric J.; Calonne, Emilie; Putmans, Pascale; Brohée, Sylvain; Olsen, Catharina; Guo, Mingzhou; Bontempi, Gianluca; Sotiriou, Christos; Defrance, Matthieu; Fuks, François

    2016-01-01

    Evidence is emerging that long noncoding RNAs (lncRNAs) may play a role in cancer development, but this role is not yet clear. We performed a genome-wide transcriptional survey to explore the lncRNA landscape across 995 breast tissue samples. We identified 215 lncRNAs whose genes are aberrantly expressed in breast tumors, as compared to normal samples. Unsupervised hierarchical clustering of breast tumors on the basis of their lncRNAs revealed four breast cancer subgroups that correlate tightly with PAM50-defined mRNA-based subtypes. Using multivariate analysis, we identified no less than 210 lncRNAs prognostic of clinical outcome. By analyzing the coexpression of lncRNA genes and protein-coding genes, we inferred potential functions of the 215 dysregulated lncRNAs. We then associated subtype-specific lncRNAs with key molecular processes involved in cancer. A correlation was observed, on the one hand, between luminal A–specific lncRNAs and the activation of phosphatidylinositol 3-kinase, fibroblast growth factor, and transforming growth factor–β pathways and, on the other hand, between basal-like–specific lncRNAs and the activation of epidermal growth factor receptor (EGFR)–dependent pathways and of the epithelial-to-mesenchymal transition. Finally, we showed that a specific lncRNA, which we called CYTOR, plays a role in breast cancer. We confirmed its predicted functions, showing that it regulates genes involved in the EGFR/mammalian target of rapamycin pathway and is required for cell proliferation, cell migration, and cytoskeleton organization. Overall, our work provides the most comprehensive analyses for lncRNA in breast cancers. Our findings suggest a wide range of biological functions associated with lncRNAs in breast cancer and provide a foundation for functional investigations that could lead to new therapeutic approaches.

  11. Portraying breast cancers with long noncoding RNAs.

    PubMed

    Van Grembergen, Olivier; Bizet, Martin; de Bony, Eric J; Calonne, Emilie; Putmans, Pascale; Brohée, Sylvain; Olsen, Catharina; Guo, Mingzhou; Bontempi, Gianluca; Sotiriou, Christos; Defrance, Matthieu; Fuks, François

    2016-09-01

    Evidence is emerging that long noncoding RNAs (lncRNAs) may play a role in cancer development, but this role is not yet clear. We performed a genome-wide transcriptional survey to explore the lncRNA landscape across 995 breast tissue samples. We identified 215 lncRNAs whose genes are aberrantly expressed in breast tumors, as compared to normal samples. Unsupervised hierarchical clustering of breast tumors on the basis of their lncRNAs revealed four breast cancer subgroups that correlate tightly with PAM50-defined mRNA-based subtypes. Using multivariate analysis, we identified no less than 210 lncRNAs prognostic of clinical outcome. By analyzing the coexpression of lncRNA genes and protein-coding genes, we inferred potential functions of the 215 dysregulated lncRNAs. We then associated subtype-specific lncRNAs with key molecular processes involved in cancer. A correlation was observed, on the one hand, between luminal A-specific lncRNAs and the activation of phosphatidylinositol 3-kinase, fibroblast growth factor, and transforming growth factor-β pathways and, on the other hand, between basal-like-specific lncRNAs and the activation of epidermal growth factor receptor (EGFR)-dependent pathways and of the epithelial-to-mesenchymal transition. Finally, we showed that a specific lncRNA, which we called CYTOR, plays a role in breast cancer. We confirmed its predicted functions, showing that it regulates genes involved in the EGFR/mammalian target of rapamycin pathway and is required for cell proliferation, cell migration, and cytoskeleton organization. Overall, our work provides the most comprehensive analyses for lncRNA in breast cancers. Our findings suggest a wide range of biological functions associated with lncRNAs in breast cancer and provide a foundation for functional investigations that could lead to new therapeutic approaches. PMID:27617288

  12. Portraying breast cancers with long noncoding RNAs

    PubMed Central

    Van Grembergen, Olivier; Bizet, Martin; de Bony, Eric J.; Calonne, Emilie; Putmans, Pascale; Brohée, Sylvain; Olsen, Catharina; Guo, Mingzhou; Bontempi, Gianluca; Sotiriou, Christos; Defrance, Matthieu; Fuks, François

    2016-01-01

    Evidence is emerging that long noncoding RNAs (lncRNAs) may play a role in cancer development, but this role is not yet clear. We performed a genome-wide transcriptional survey to explore the lncRNA landscape across 995 breast tissue samples. We identified 215 lncRNAs whose genes are aberrantly expressed in breast tumors, as compared to normal samples. Unsupervised hierarchical clustering of breast tumors on the basis of their lncRNAs revealed four breast cancer subgroups that correlate tightly with PAM50-defined mRNA-based subtypes. Using multivariate analysis, we identified no less than 210 lncRNAs prognostic of clinical outcome. By analyzing the coexpression of lncRNA genes and protein-coding genes, we inferred potential functions of the 215 dysregulated lncRNAs. We then associated subtype-specific lncRNAs with key molecular processes involved in cancer. A correlation was observed, on the one hand, between luminal A–specific lncRNAs and the activation of phosphatidylinositol 3-kinase, fibroblast growth factor, and transforming growth factor–β pathways and, on the other hand, between basal-like–specific lncRNAs and the activation of epidermal growth factor receptor (EGFR)–dependent pathways and of the epithelial-to-mesenchymal transition. Finally, we showed that a specific lncRNA, which we called CYTOR, plays a role in breast cancer. We confirmed its predicted functions, showing that it regulates genes involved in the EGFR/mammalian target of rapamycin pathway and is required for cell proliferation, cell migration, and cytoskeleton organization. Overall, our work provides the most comprehensive analyses for lncRNA in breast cancers. Our findings suggest a wide range of biological functions associated with lncRNAs in breast cancer and provide a foundation for functional investigations that could lead to new therapeutic approaches. PMID:27617288

  13. Dependence of AT1 angiotensin receptor function on adjacent asparagine residues in the seventh transmembrane helix.

    PubMed

    Hunyady, L; Ji, H; Jagadeesh, G; Zhang, M; Gáborik, Z; Mihalik, B; Catt, K J

    1998-08-01

    For several G protein-coupled receptors, amino acids in the seventh transmembrane helix have been implicated in ligand binding and receptor activation. The function of this region in the AT1 angiotensin receptor was further investigated by mutation of two conserved polar residues (Asn294 and Asn295) and the adjacent Phe293 residue. Analysis of the properties of the mutant receptors expressed in COS-7 cells revealed that alanine replacement of Phe293 had no major effect on AT1 receptor function. Substitution of the adjacent Asn294 residue with alanine (N294A) reduced receptor binding affinities for angiotensin II, two nonpeptide agonists (L-162,313 and L-163,491), and the AT1-selective nonpeptide antagonist losartan but not that for the peptide antagonist [Sar1, Ile8]angiotensin II. The N294A receptor also showed impaired G protein coupling and severely attenuated inositol phosphate generation. In contrast, alanine replacement of Asn295 decreased receptor binding affinities for all angiotensin II ligands but did not impair signal transduction. Additional substitutions of Asn295 with a variety of amino acids did not identify specific structural elements for ligand binding. These findings indicate that Asn295 is required for the integrity of the intramembrane binding pocket of the AT1a receptor but is not essential for signal generation. They also demonstrate the importance of transmembrane helices in the formation of the binding site for nonpeptide AT1 receptor agonists. We conclude that the Asn294 residue of the AT1 receptor is an essential determinant of receptor activation and that the adjacent Asn295 residue is required for normal ligand binding.

  14. No association between Epstein-Barr Virus and Mouse Mammary Tumor Virus with Breast Cancer in Mexican Women

    NASA Astrophysics Data System (ADS)

    Morales-Sánchez, Abigail; Molina-Muñoz, Tzindilú; Martínez-López, Juan L. E.; Hernández-Sancén, Paulina; Mantilla, Alejandra; Leal, Yelda A.; Torres, Javier; Fuentes-Pananá, Ezequiel M.

    2013-10-01

    Breast cancer is the most frequent malignancy affecting women worldwide. It has been suggested that infection by Epstein Barr Virus (EBV), Mouse Mammary Tumor Virus or a similar virus, MMTV-like virus (MMTV-LV), play a role in the etiology of the disease. However, studies looking at the presence of these viruses in breast cancer have produced conflicting results, and this possible association remains controversial. Here, we used polymerase chain reaction assay to screen specific sequences of EBV and MMTV-LV in 86 tumor and 65 adjacent tissues from Mexican women with breast cancer. Neither tumor samples nor adjacent tissue were positive for either virus in a first round PCR and only 4 tumor samples were EBV positive by a more sensitive nested PCR. Considering the study's statistical power, these results do not support the involvement of EBV and MMTV-LV in the etiology of breast cancer.

  15. No association between Epstein-Barr Virus and Mouse Mammary Tumor Virus with Breast Cancer in Mexican Women

    PubMed Central

    Morales-Sánchez, Abigail; Molina-Muñoz, Tzindilú; Martínez-López, Juan L. E.; Hernández-Sancén, Paulina; Mantilla, Alejandra; Leal, Yelda A.; Torres, Javier; Fuentes-Pananá, Ezequiel M.

    2013-01-01

    Breast cancer is the most frequent malignancy affecting women worldwide. It has been suggested that infection by Epstein Barr Virus (EBV), Mouse Mammary Tumor Virus or a similar virus, MMTV-like virus (MMTV-LV), play a role in the etiology of the disease. However, studies looking at the presence of these viruses in breast cancer have produced conflicting results, and this possible association remains controversial. Here, we used polymerase chain reaction assay to screen specific sequences of EBV and MMTV-LV in 86 tumor and 65 adjacent tissues from Mexican women with breast cancer. Neither tumor samples nor adjacent tissue were positive for either virus in a first round PCR and only 4 tumor samples were EBV positive by a more sensitive nested PCR. Considering the study's statistical power, these results do not support the involvement of EBV and MMTV-LV in the etiology of breast cancer. PMID:24131889

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

    ClinicalTrials.gov

    2016-03-16

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

  17. Breast Reconstruction after Mastectomy

    PubMed Central

    Schmauss, Daniel; Machens, Hans-Günther; Harder, Yves

    2016-01-01

    Breast cancer is the leading cause of cancer death in women worldwide. Its surgical approach has become less and less mutilating in the last decades. However, the overall number of breast reconstructions has significantly increased lately. Nowadays, breast reconstruction should be individualized at its best, first of all taking into consideration not only the oncological aspects of the tumor, neo-/adjuvant treatment, and genetic predisposition, but also its timing (immediate versus delayed breast reconstruction), as well as the patient’s condition and wish. This article gives an overview over the various possibilities of breast reconstruction, including implant- and expander-based reconstruction, flap-based reconstruction (vascularized autologous tissue), the combination of implant and flap, reconstruction using non-vascularized autologous fat, as well as refinement surgery after breast reconstruction. PMID:26835456

  18. Innovative biomagnetic imaging sensors for breast cancer: A model-based study

    SciTech Connect

    Deng, Y.; Golkowski, M.

    2012-04-01

    Breast cancer is a serious potential health problem for all women and is the second leading cause of cancer deaths in the United States. The current screening procedures and imaging techniques, including x-ray mammography, clinical biopsy, ultrasound imaging, and magnetic resonance imaging, provide only 73% accuracy in detecting breast cancer. This gives the impetus to explore alternate techniques for imaging the breast and detecting early stage tumors. Among the complementary methods, the noninvasive biomagnetic breast imaging is attractive and promising, because both ionizing radiation and breast compressions that the prevalent x-ray mammography suffers from are avoided. It furthermore offers very high contrast because of the significant electromagnetic properties' differences between the cancerous, benign, and normal breast tissues. In this paper, a hybrid and accurate modeling tool for biomagnetic breast imaging is developed, which couples the electromagnetic and ultrasonic energies, and initial validations between the model predication and experimental findings are conducted.

  19. Breast fat and fallacies: more than 100 years of anatomical fantasy.

    PubMed

    Nickell, William B; Skelton, Jackie

    2005-05-01

    The authors studied the anatomy of 136 patients who underwent breast reduction surgery from 1998 to 2003 to determine the relationship of breast fat to the glandular tissue of the breast. Histological sections of freshly preserved breast tissue taken from representative patients were examined and compared to depictions of normal breast anatomy as portrayed in standard anatomical texts from the classic work of Sir Astley Cooper in 1845 to current publications such as Auberbach and Riordan's Breastfeeding and Human Lactation. Most texts portray little intermix of fat with the glandular tissue of the breast. Our studies confirm the texts that demonstrate the fat and glandular tissue to be inseparable and present in continuity with each other except in the subcutaneous plane where only fat is present. The implications of this anatomical fact as it relates to breast surgery and human lactation are discussed.

  20. Population of 100 realistic, patient-based computerized breast phantoms for multi-modality imaging research

    NASA Astrophysics Data System (ADS)

    Segars, W. Paul; Veress, Alexander I.; Wells, Jered R.; Sturgeon, Gregory M.; Kiarashi, Nooshin; Lo, Joseph Y.; Samei, Ehsan; Dobbins, James T.

    2014-03-01

    Breast imaging is an important area of research with many new techniques being investigated to further reduce the morbidity and mortality of breast cancer through early detection. Computerized phantoms can provide an essential tool to quantitatively compare new imaging systems and techniques. Current phantoms, however, lack sufficient realism in depicting the complex 3D anatomy of the breast. In this work, we created one-hundred realistic and detailed 3D computational breast phantoms based on high-resolution CT datasets from normal patients. We also developed a finiteelement application to simulate different compression states of the breast, making the phantoms applicable to multimodality imaging research. The breast phantoms and tools developed in this work were packaged into user-friendly software applications to distribute for breast imaging research.