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Sample records for breast tissue plasma

  1. Comparison of ESR1 Mutations in Tumor Tissue and Matched Plasma Samples from Metastatic Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Takashi Takeshita

    2017-10-01

    Full Text Available BACKGROUND: ESR1 mutation in circulating cell-free DNA (cfDNA is emerging as a noninvasive biomarker of acquired resistance to endocrine therapy, but there is a paucity of data comparing the status of ESR1 gene in cfDNA with that in its corresponding tumor tissue. The objective of this study is to validate the degree of concordance of ESR1 mutations between plasma and tumor tissue. METHODS: ESR1 ligand-binding domain mutations Y537S, Y537N, Y537C, and D538G were analyzed using droplet digital PCR in 35 patients with metastatic breast cancer (MBC (35 tumor tissue samples and 67 plasma samples. RESULTS: Of the 35 paired samples, 26 (74.3% were concordant: one patient had detectable ESR1 mutations both plasma (ESR1 Y537S/Y537N and tumor tissue (ESR1 Y537S/Y537C, and 25 had WT ESR1 alleles in both. Nine (25.7% had discordance between the plasma and tissue results: five had mutations detected only in their tumor tissue (two Y537S, one Y537C, one D538G, and one Y537S/Y537N/D538G, and four had mutations detected only in their plasma (one Y537S, one Y537N, and two Y537S/Y537N/D538G. Furthermore, longitudinal plasma samples from 19 patients were used to assess changes in the presence of ESR1 mutations during treatment. Eleven patients had cfDNA ESR1 mutations over the course of treatment. A total of eight of 11 patients with MBC with cfDNA ESR1 mutations (72.7% had the polyclonal mutations. CONCLUSION: We have shown the independent distribution of ESR1 mutations between plasma and tumor tissue in 35 patients with MBC.

  2. Breast reconstruction - natural tissue

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    ... another method called the free flap procedure, skin, fat, and muscle tissue are removed from your lower belly. This tissue ... breast that was removed. The surgeon loosens skin, fat, and muscle from this area. This tissue is then tunneled under your skin to the ...

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

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    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.

  4. Oestrone sulphate, adipose tissue, and breast cancer.

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    Hawkins, R A; Thomson, M L; Killen, E

    1985-01-01

    Oestrone sulphate, the oestrogen in highest concentration in the plasma, may play a role in the induction and growth of breast cancers. By enzymolysis and radioimmunoassay, oestrone sulphate concentrations were measured in 3 biological fluids. High concentrations of the conjugate (up to 775 nmol/l) were detected in breast cyst fluids from some premenopausal women, the concentrations in blood plasma (0.91-4.45 nmol/l) being much lower. Concentrations in the plasmas from postmenopausal women with (0.23-4.63 nmol/l) or without (0.18-1.27 nmol/l) breast cancer were still lower. Oestrone sulphate concentration in cow's milk or cream (0.49-0.67 nmol/l) was also low: dietary intake in these fluids is probably of little consequence. The capacity of breast tissues for hydrolysis of oestrone sulphate was examined in two ways: In tissue slices incubated with 85 pM (3H) oestrone sulphate solution at 37 degrees C, cancers (131-412 fmol/g tissue/hr) and adipose tissues (23-132 fmol/g tissue/hr) hydrolysed significantly more sulphate than did benign tissues (1-36 fmol/g tissue/hr). In tissue homogenates incubated with 5-25 microM [3H] oestrone sulphate at 37 degrees much higher capacities for hydrolysis (nmol/g tissue/hr) were demonstrated with a Km of 2-16.5 microM: cancers (34-394) and benign tissues (9-485) had significantly higher sulphatase activities than adipose tissues (9-39). On a protein basis, however, the sulphatase activities in the 3 tissues were comparable. It is concluded that oestrone sulphate is present in breast cysts and blood plasma and that in vitro, the conjugated hormone can be hydrolysed by breast tissues. The biological significance of these findings in vivo remains to be established.

  5. Aluminium in human breast tissue.

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    Exley, Christopher; Charles, Lisa M; Barr, Lester; Martin, Claire; Polwart, Anthony; Darbre, Philippa D

    2007-09-01

    Aluminium is omnipresent in everyday life and increased exposure is resulting in a burgeoning body burden of this non-essential metal. Personal care products are potential contributors to the body burden of aluminium and recent evidence has linked breast cancer with aluminium-based antiperspirants. We have used graphite furnace atomic absorption spectrometry (GFAAS) to measure the aluminium content in breast biopsies obtained following mastectomies. The aluminium content of breast tissue and breast tissue fat were in the range 4-437 nmol/g dry wt. and 3-192 nmol/g oil, respectively. The aluminium content of breast tissue in the outer regions (axilla and lateral) was significantly higher (P=0.033) than the inner regions (middle and medial) of the breast. Whether differences in the regional distribution of aluminium in the breast are related to the known higher incidence of tumours in the outer upper quadrant of the breast remains to be ascertained.

  6. Effects of chromium-enriched bacillus subtilis KT260179 supplementation on chicken growth performance, plasma lipid parameters, tissue chromium levels, cecal bacterial composition and breast meat quality.

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    Yang, Jiajun; Qian, Kun; Zhang, Wei; Xu, Yayuan; Wu, Yijing

    2016-11-08

    Both chromium (Cr) and probiotic bacillus own the virtues of regulating animal metabolism and meat quality. Purpose of this study was to evaluate the efficiency of supplemental Cr and bacillus in the form of chromium-enriched Bacillus subtilis KT260179 (CEBS) on chicken growth performance, plasma lipid parameters, tissue chromium levels, cecal bacterial composition and breast meat quality. Six hundred of 1-day-old Chinese Huainan Partridge chickens were divided into four groups randomly: Control, inorganic Cr, Bacillus subtilis, and CEBS. The feed duration was 56 days. After 28 days of treatment, broiler feed CEBS or normal B. subtilis had higher body weights than control broiler, and after 56 days, chickens given either CEBS or B. subtilis had greater body weights than control broiler or those given inorganic Cr. Plasma total cholesterol, triglycerides, and low density lipoprotein cholesterol levels declined significantly in the CEBS group compared with the control, whereas plasma high density lipoprotein cholesterol levels increased significantly. The concentration of Cr in blood and breast muscle increased after CEBS and inorganic Cr supplementation. B. subtilis and CEBS supplementation caused a significant increase in the numbers of Lactobacillus and Bifidobacterium in the caecum, while the numbers of Escherichia coli and Salmonella decreased significantly compared to the control. Feed adding CEBS increased the lightness, redness, and yellowness of breast meat, improved the water-holding capacity, decreased the shear force and cooking loss. In all, CEBS supplementation promoted body growth, improved plasma lipid parameters, increased tissue Cr concentrations, altered cecal bacterial composition and improved breast meat quality.

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

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

    2015-11-15

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

  8. Diagnosis of breast cancer by tissue analysis

    Institute of Scientific and Technical Information of China (English)

    Debnath Bhattacharyya; Samir Kumar Bandyopadhyay; Tai-hoon Kim

    2013-01-01

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

  9. Breast Tissue Composition and Susceptibility to Breast Cancer

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

    2010-01-01

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

  10. Accessory breast tissue in axilla masquerading as breast cancer recurrence

    Directory of Open Access Journals (Sweden)

    Goyal Shikha

    2008-01-01

    Full Text Available Ectopic or accessory breast tissue is most commonly located in the axilla, though it may be present anywhere along the milk line. Development is hormone dependent, similar to normal breast tissue. These lesions do not warrant any intervention unless they produce discomfort, thus their identification and distinction from other breast pathologies, both benign and malignant, is essential. We report a case with locally advanced breast cancer who presented with an ipsilateral axillary mass following surgery, radiotherapy, and chemotherapy. Subsequent evaluation with excision biopsy showed duct ectasia in axillary breast tissue and the patient was continued on hormone therapy with tamoxifen.

  11. Breast Imaging after Breast Augmentation with Autologous Tissues

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    Hwang, Kyu Won; Seo, Bo Kyung; Shim, Eddeum; Song, Sung Eun; Cho, Kyu Ran [Dept. of Radiology, Korea University Anam Hospital, Seoul (Korea, Republic of); Yoon, Eul Sik [Korea University Ansan Hospital, Ansan (Korea, Republic of); Woo, Ok Hee [Dept. of Radiology, Korea University Guro Hospital, Seoul (Korea, Republic of)

    2012-06-15

    The use of autologous tissue transfer for breast augmentation is an alternative to using foreign implant materials. The benefits of this method are the removal of unwanted fat from other body parts, no risk of implant rupture, and the same feel as real breast tissue. However, sometimes there is a dilemma about whether or not to biopsy for calcifications or masses detected after the procedure is completed. The purpose of this study is to illustrate the procedures of breast augmentation with autologous tissues, the imaging features of various complications, and the role of imaging in the diagnosis and management of complications and hidden breast diseases.

  12. Zinc isotopic compositions of breast cancer tissue.

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    Larner, Fiona; Woodley, Laura N; Shousha, Sami; Moyes, Ashley; Humphreys-Williams, Emma; Strekopytov, Stanislav; Halliday, Alex N; Rehkämper, Mark; Coombes, R Charles

    2015-01-01

    An early diagnostic biomarker for breast cancer is essential to improve outcome. High precision isotopic analysis, originating in Earth sciences, can detect very small shifts in metal pathways. For the first time, the natural intrinsic Zn isotopic compositions of various tissues in breast cancer patients and controls were determined. Breast cancer tumours were found to have a significantly lighter Zn isotopic composition than the blood, serum and healthy breast tissue in both groups. The Zn isotopic lightness in tumours suggests that sulphur rich metallothionein dominates the isotopic selectivity of a breast tissue cell, rather than Zn-specific proteins. This reveals a possible mechanism of Zn delivery to Zn-sequestering vesicles by metallothionein, and is supported by a similar signature observed in the copper isotopic compositions of one breast cancer patient. This change in intrinsic isotopic compositions due to cancer has the potential to provide a novel early biomarker for breast cancer.

  13. Ultrasound tomography of breast tissue

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    Duric, Nebojsa; Littrup, Peter J.; Holsapple, Earle; Babkin, Alex; Duncan, Robert; Kalinin, Arkady; Pevzner, Roman; Tokarev, Michael

    2003-05-01

    The Karmanos Cancer Institute is developing an ultrasound device for measuring and imaging acoustic parameters of human tissue. This paper discusses the experimental results relating to tomographic reconstructions of phantoms and tissue. The specimens were scanned by the prototype scanner at a frequency of 1.5 MHz using 2 microsecond pulses. The receivers and transmitters were positioned along a ring trajectory having a diameter of 20 cm. The ring plane is translated in the vertical direction allowing for 3-D reconstructions from stacked 2-D planes of data. All ultrasound scans were performed at 10 millimeter slice thickness to generate multiple tomographic images. In a previous SPIE paper we presented preliminary results of ultrasound tomographic reconstruction of formalin-fixed breast tissue. We now present new results from data acquired with the scanner. Images were constructed using both reflection-based and transmission based algorithms. The resulting images demonstrate the ability to detect sub-mm features and to measure acoustic properties such as sound speed. Comparison with conventional ultrasound indicates the potential for better margin definition and acoustic characterization of tissue.

  14. Studies of vegans: the fatty acid composition of plasma choline phosphoglycerides, erythrocytes, adipose tissue, and breast milk, and some indicators of susceptibility to ischemic heart disease in vegans and omnivore controls.

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    Sanders, T A; Ellis, F R; Dickerson, J W

    1978-05-01

    The fatty acid composition of erythrocytes, of plasma choline phosphoglycerides, and of adipose tissue, serum cholesterol, triglyceride and vitamin B12 concentrations, weights, heights and skinfold thickness were determined on 22 vegans and 22 age and sex matched omnivore controls. The fatty acid composition of breast milk from four vegan and four omnivore control mothers, and of erythrocytes from three infants breast fed by vegan mothers and six infants breast fed by omnivore control mothers was determined. The proportions of linoleic acid and its long-chain derivatives were higher, the proportion of the long-chain derivatives of alpha-linolenic acid was lower, and the ratio of 22:5omega3/22:6omega3 was greater in the tissues of the vegans and infants breast-fed by vegans than in controls; the most marked differences were in the proportions of linoleic (18:2omega6) and docosahexenoic (22:6omega3) acids. Weights, skinfold thickness, serum vitamin B12, cholesterol and triglyceride concentrations were less in vegans than in controls. The difference in serum cholesterol concentration was most marked. It is concluded that a vegan-type diet may be the one of choice in the treatment of ischemic heart disease, angina pectoris, and certain hyperlipidemias.

  15. Breast muscle tissue characteristics in growing broilers

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    Muscle cell development in broilers influences growth rate, breast meat yield, and meat quality. The objective of this study was to characterize muscle tissue changes in breast muscles from two commercial lines of broilers from 21 to 56 days of age. The experiment was designed as a 2×2×6 factorial...

  16. Silicone breast implants and connective tissue disease

    DEFF Research Database (Denmark)

    Lipworth, Loren; Holmich, Lisbet R; McLaughlin, Joseph K

    2011-01-01

    The association of silicone breast implants with connective tissue diseases (CTDs), including systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, and fibromyalgia, as well as a hypothesized new "atypical" disease, which does not meet established diagnostic criteria for any known...

  17. [Differential scanning calorimetry of blood plasma in breast cancer patients].

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    Zapf, István; Fekecs, Tamás; Moezzi, Medhi; Tizedes, György; Pavlovics, Gábor; Kálmán, Endre; Horváth, Péter Ors; Ferencz, Andrea

    2012-12-01

    Breast cancer is the commonest cause of cancer death in women worldwide. Its incidence has been increasing for many years in economically developed countries. Differential scanning calorimetry (DSC) is a thermoanalytical technique which monitors small heat changes between sample and reference materials. This examination is a validly efficient method for the demonstration of structural changes not only in the physical sciences, but in numerous human oncological diseases. The goal of this study was to measure DSC thermogram of blood plasma in breast cancer patients with different stages. Nineteen women with different tumor diameter (0.5-7.5 mm) and with or without regional lymph node metastases were involved in the study. Preoperatively peripheral blood samples were collected from the patients and from healthy controls, and plasma components were analysed by SETARAM micro DSC-II calorimeter. The diameter of the tumor tissue and the number of metastatic lymph nodes were evaluated on the basis of postoperative histological results. In the current study we found difference in changes of the thermal parameters (transition temperature, calorimetric enthalpy) of breast cancer patients' plasma components. Moreover, a tendency has been found for association of these results with tumor size and with the degree of regional lymph node involvement. Preliminary study of the clinical utility of DSC technology arises, even though there is no data in the literature. In cases of breast cancer the blood plasma may be suitable for DSC analysis for diagnosis or staging as well. In order to clarify the relationships we are planning further studies.

  18. The a3 isoform of subunit a of the vacuolar ATPase localizes to the plasma membrane of invasive breast tumor cells and is overexpressed in human breast cancer.

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    Cotter, Kristina; Liberman, Rachel; Sun-Wada, GeHong; Wada, Yoh; Sgroi, Dennis; Naber, Stephen; Brown, Dennis; Breton, Sylvie; Forgac, Michael

    2016-07-19

    The vacuolar (H+)-ATPases (V-ATPases) are a family of ATP-driven proton pumps that acidify intracellular compartments and transport protons across the plasma membrane. Previous work has demonstrated that plasma membrane V-ATPases are important for breast cancer invasion in vitro and that the V-ATPase subunit a isoform a3 is upregulated in and critical for MDA-MB231 and MCF10CA1a breast cancer cell invasion. It has been proposed that subunit a3 is present on the plasma membrane of invasive breast cancer cells and is overexpressed in human breast cancer. To test this, we used an a3-specific antibody to assess localization in breast cancer cells. Subunit a3 localizes to the leading edge of migrating breast cancer cells, but not the plasma membrane of normal breast epithelial cells. Furthermore, invasive breast cancer cells express a3 throughout all intracellular compartments tested, including endosomes, the Golgi, and lysosomes. Moreover, subunit a3 knockdown in MB231 breast cancer cells reduces in vitro migration. This reduction is not enhanced upon addition of a V-ATPase inhibitor, suggesting that a3-containing V-ATPases are critical for breast cancer migration. Finally, we have tested a3 expression in human breast cancer tissue and mRNA prepared from normal and cancerous breast tissue. a3 mRNA was upregulated 2.5-47 fold in all breast tumor cDNA samples tested relative to normal tissue, with expression generally correlated to cancer stage. Furthermore, a3 protein expression was increased in invasive breast cancer tissue relative to noninvasive cancer and normal breast tissue. These studies suggest that subunit a3 plays an important role in invasive human breast cancer.

  19. Relationships of sex steroid hormone levels in benign and cancerous breast tissue and blood: A critical appraisal of current science.

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    Stanczyk, Frank Z; Mathews, Brett W; Sherman, Mark E

    2015-07-01

    A systematic review of the literature on sex steroid measurement in breast tissue identified only 19 articles meeting the following criteria: menopausal status given; steroids measured in tissue homogenates by conventional RIA with a purification step or by mass spectrometry; and values reported per g tissue or per g protein. Twelve articles were analyzed in detail for: ratios of sex steroid hormone levels in cancerous or benign tissues to blood levels, stratified by menopausal status; ratios between the different hormone levels within tissues or within blood; and difference in these ratios between tissue and blood compartments. Estrogen and androgen concentrations varied greatly in benign and cancerous tissues and in blood between individuals. Postmenopausal, but not premenopausal, estradiol concentrations were significantly higher in cancerous compared to benign breast tissue. The estradiol/estrone ratio was lowest in premenopausal benign tissue, and substantially higher in premenopausal cancerous tissue and postmenopausal benign and cancerous tissues. Estradiol and estrone levels were considerably higher in tissue than in plasma in both premenopausal and postmenopausal women. Androgen levels were generally higher in the benign than the cancerous tissue, and tissue androgen levels were higher than in plasma, suggesting in situ aromatization of androgens to estrogens in breast cancer tissue. Limited available data on levels of hydroxylated estrogens in breast tissue compared to corresponding levels in plasma or urine were reviewed, but due to the paucity of studies no conclusions can presently be drawn regarding the relationship of the 2-hydroxyestrone:16α-hydroxyestrone ratio to breast cancer risk and genotoxic effects of 4-hydroxylated estrogens. Finally, data on hormone levels in breast adipose tissue were analyzed; high levels of androstenedione and testosterone and significant estrone and estradiol levels in breast adipocytes from postmenopausal breast

  20. Lubricin in human breast tissue expander capsules.

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    Cheriyan, Thomas; Guo, Lifei; Orgill, Dennis P; Padera, Robert F; Schmid, Thomas M; Spector, Myron

    2012-10-01

    Capsular contraction is the most common complication of breast reconstruction surgery. While presence of the contractile protein alpha smooth muscle actin (α-SMA) is considered among the causes of capsular contraction, the exact etiology and pathophysiology is not fully understood. The objective of this study was to investigate the possible role of lubricin in capsular formation and contraction by determining the presence and distribution of the lubricating protein lubricin in human breast tissue expander capsules. Related aims were to evaluate select histopathologic features of the capsules, and the percentage of cells expressing α-SMA, which reflects the myofibroblast phenotype. Capsules from tissue expanders were obtained from eight patients. Lubricin, at the tissue-implant interface, in the extracellular matrix, and in cells, and α-SMA-containing cells were evaluated immunohistochemically. The notable finding was that lubricin was identified in all tissue expander capsules: as a discrete layer at the tissue-implant interface, extracellular, and intracellular. There was a greater amount of lubricin in the extracellular matrix in the intimal-subintimal zone when compared with the tissue away from the implant. Varying degrees of synovial metaplasia were seen at the tissue-implant interface. α-SMA-containing cells were also seen in all but one patient. The findings might help us better understand factors involved in capsule formation.

  1. Generation of 3D synthetic breast tissue

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    Elangovan, Premkumar; Dance, David R.; Young, Kenneth C.; Wells, Kevin

    2016-03-01

    Virtual clinical trials are an emergent approach for the rapid evaluation and comparison of various breast imaging technologies and techniques using computer-based modeling tools. A fundamental requirement of this approach for mammography is the use of realistic looking breast anatomy in the studies to produce clinically relevant results. In this work, a biologically inspired approach has been used to simulate realistic synthetic breast phantom blocks for use in virtual clinical trials. A variety of high and low frequency features (including Cooper's ligaments, blood vessels and glandular tissue) have been extracted from clinical digital breast tomosynthesis images and used to simulate synthetic breast blocks. The appearance of the phantom blocks was validated by presenting a selection of simulated 2D and DBT images interleaved with real images to a team of experienced readers for rating using an ROC paradigm. The average areas under the curve for 2D and DBT images were 0.53+/-.04 and 0.55+/-.07 respectively; errors are the standard errors of the mean. The values indicate that the observers had difficulty in differentiating the real images from simulated images. The statistical properties of simulated images of the phantom blocks were evaluated by means of power spectrum analysis. The power spectrum curves for real and simulated images closely match and overlap indicating good agreement.

  2. Objective breast tissue image classification using Quantitative Transmission ultrasound tomography

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    Malik, Bilal; Klock, John; Wiskin, James; Lenox, Mark

    2016-12-01

    Quantitative Transmission Ultrasound (QT) is a powerful and emerging imaging paradigm which has the potential to perform true three-dimensional image reconstruction of biological tissue. Breast imaging is an important application of QT and allows non-invasive, non-ionizing imaging of whole breasts in vivo. Here, we report the first demonstration of breast tissue image classification in QT imaging. We systematically assess the ability of the QT images’ features to differentiate between normal breast tissue types. The three QT features were used in Support Vector Machines (SVM) classifiers, and classification of breast tissue as either skin, fat, glands, ducts or connective tissue was demonstrated with an overall accuracy of greater than 90%. Finally, the classifier was validated on whole breast image volumes to provide a color-coded breast tissue volume. This study serves as a first step towards a computer-aided detection/diagnosis platform for QT.

  3. Cold atmospheric plasma for selectively ablating metastatic breast cancer cells.

    Science.gov (United States)

    Wang, Mian; Holmes, Benjamin; Cheng, Xiaoqian; Zhu, Wei; Keidar, Michael; Zhang, Lijie Grace

    2013-01-01

    Traditional breast cancer treatments such as surgery and radiotherapy contain many inherent limitations with regards to incomplete and nonselective tumor ablation. Cold atmospheric plasma (CAP) is an ionized gas where the ion temperature is close to room temperature. It contains electrons, charged particles, radicals, various excited molecules, UV photons and transient electric fields. These various compositional elements have the potential to either enhance and promote cellular activity, or disrupt and destroy them. In particular, based on this unique composition, CAP could offer a minimally-invasive surgical approach allowing for specific cancer cell or tumor tissue removal without influencing healthy cells. Thus, the objective of this research is to investigate a novel CAP-based therapy for selectively bone metastatic breast cancer treatment. For this purpose, human metastatic breast cancer (BrCa) cells and bone marrow derived human mesenchymal stem cells (MSCs) were separately treated with CAP, and behavioral changes were evaluated after 1, 3, and 5 days of culture. With different treatment times, different BrCa and MSC cell responses were observed. Our results showed that BrCa cells were more sensitive to these CAP treatments than MSCs under plasma dose conditions tested. It demonstrated that CAP can selectively ablate metastatic BrCa cells in vitro without damaging healthy MSCs at the metastatic bone site. In addition, our study showed that CAP treatment can significantly inhibit the migration and invasion of BrCa cells. The results suggest the great potential of CAP for breast cancer therapy.

  4. Cold atmospheric plasma for selectively ablating metastatic breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Mian Wang

    Full Text Available Traditional breast cancer treatments such as surgery and radiotherapy contain many inherent limitations with regards to incomplete and nonselective tumor ablation. Cold atmospheric plasma (CAP is an ionized gas where the ion temperature is close to room temperature. It contains electrons, charged particles, radicals, various excited molecules, UV photons and transient electric fields. These various compositional elements have the potential to either enhance and promote cellular activity, or disrupt and destroy them. In particular, based on this unique composition, CAP could offer a minimally-invasive surgical approach allowing for specific cancer cell or tumor tissue removal without influencing healthy cells. Thus, the objective of this research is to investigate a novel CAP-based therapy for selectively bone metastatic breast cancer treatment. For this purpose, human metastatic breast cancer (BrCa cells and bone marrow derived human mesenchymal stem cells (MSCs were separately treated with CAP, and behavioral changes were evaluated after 1, 3, and 5 days of culture. With different treatment times, different BrCa and MSC cell responses were observed. Our results showed that BrCa cells were more sensitive to these CAP treatments than MSCs under plasma dose conditions tested. It demonstrated that CAP can selectively ablate metastatic BrCa cells in vitro without damaging healthy MSCs at the metastatic bone site. In addition, our study showed that CAP treatment can significantly inhibit the migration and invasion of BrCa cells. The results suggest the great potential of CAP for breast cancer therapy.

  5. Direct plasma interaction with living tissue

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    Fridman, Gregory

    For some time, plasma has been used in medicine to cauterize or cut tissue using heat and mechanical energy. In the recent decade, some researchers around the world have started to investigate how gas jets that pass through thermal plasma can be employed in medicine. This thesis presents the first investigation of biomedical uses of non-thermal plasma discharge which comes in direct contact with living tissue. It is demonstrated that the direct application of non-thermal plasma in air can cause rapid deactivation of bacteria on surfaces of tissues without causing any visible tissue damage. Medical need for such a device is discussed. Construction and operation of various types of non-thermal plasma power supplies and many types of treatment electrodes are presented as well. Application of this plasma to living organisms is shown to be safe from both the electrical perspective and from the biological perspective. Biological safety is revealed through a series of differential skin toxicity trials on human cadaver tissue, live hairless mouse skin tissue, live pig skin tissue, and finally in an open wound model on pigs. Direct non-thermal plasma in air is shown to deactivate bacteria about 100 times faster than indirect application using jets. A series of experiments reveal that this effectiveness is due to the ability of direct discharge to bring charges to tissue surfaces. It is demonstrated that neither ultraviolet (UV) radiation nor neutral active species such as hydroxyl radicals or ozone produced in plasma are responsible for the main effect on bacteria. Although much additional work remains on establishing detailed mechanism by which charges from plasma achieve this effect, the work carried out in this thesis clearly demonstrates that direct application of non-thermal plasma in air can be a very useful tool in medicine.

  6. Human breast biomonitoring and environmental chemicals: use of breast tissues and fluids in breast cancer etiologic research.

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    LaKind, Judy S; Wilkins, Amy A; Bates, Michael N

    2007-09-01

    Extensive research indicates that the etiology of breast cancer is complex and multifactorial and may include environmental risk factors. Breast cancer etiology and exposure to xenobiotic compounds, diet, electromagnetic fields, and lifestyle have been the subject of numerous scientific inquiries, but research has yielded inconsistent results. Biomonitoring has been used to explore associations between breast cancer and levels of environmental chemicals in the breast. Research using breast tissues and fluids to cast light on the etiology of breast cancer is, for the most part, predicated on the assumption that the tissue or fluid samples either contain measurable traces of the environmental agent(s) associated with the cancer or that they retain biological changes that are biomarkers of such exposure or precursors of carcinogenic effect. In this paper, we review breast cancer etiology research utilizing breast biomonitoring. We first provide a brief synopsis of the current state of understanding of associations between exposure to environmental chemicals and breast cancer etiology. We then describe the published breast cancer research on tissues and fluids, which have been used for biomonitoring, specifically human milk and its components, malignant and benign breast tissue, nipple aspirate fluid (NAF) and breast cyst fluid. We conclude with a discussion on recommendations for biomonitoring of breast tissues and fluids in future breast cancer etiology research. Both human milk and NAF fluids, and the cells contained therein, hold promise for future biomonitoring research into breast cancer etiology, but must be conducted with carefully delineated hypotheses and a scientifically supportable epidemiological approach.

  7. Interleukin 18 expression in the primary breast cancer tumour tissue

    Directory of Open Access Journals (Sweden)

    Nahida Srabović

    2011-02-01

    Full Text Available Aim To investigate the presence and expression levels of the IL-18 in the primary breast cancer tissue in relation to the unchangedbreast tissue in same patients and the breast tissue in patients withbenign breast disease, as well as the correlation between the IL-18 expression levels and pathohistological factors, including thecorrelation between IL-18 expression and the estrogens and progesterone receptor status. Methods This prospective randomized study was conducted at the Policlinic for Laboratory Diagnostics of the University Clinical Centre of Tuzla. 50 patients with invasive ductal breast cancer and 20 patients with benign breast diseases were included in the study. The tree-step immunohistochemical staining was used for testing the levels of IL-18 expression and hormone receptor status. Results IL-18 was present in the breast cancer tumour, in the surrounding unchanged tissue of the same patients and in the breast tissue of patients with benign breast tumour and other benign breast disease. The expression of this interleukin was signiicantly higher in breast cancer tumour tissue as compared to its expression in surrounding unchanged tissue of the same patients (p<0,05, whereas IL-18 expression was not signiicantly higher in breast cancer tumours compared to its expression in breast tissue of the patients with benign breast diseases (p=0,057. There was no signiicant correlation between IL-18 expression and the lymph node status, and between IL-18 expression and the pathohistological factors. Conclusion The results suggest possible involvement of IL-18 in complex mechanisms of breast carcinogenesis.

  8. Using Data Fusion to Characterize Breast Tissue

    Energy Technology Data Exchange (ETDEWEB)

    Littrup, P; Duric, N; Leach, R R; Azevedo, S G; Candy, J V; Moore, T; Chambers, D H; Mast, J E; Johnson, S A; Holsapple, E

    2002-01-23

    New ultrasound data, obtained with a circular experimental scanner, are compared with data obtained with standard X-ray CT. Ultrasound data obtained by scanning fixed breast tissue were used to generate images of sound speed and reflectivity. The ultrasound images exhibit approximately 1 mm resolution and about 20 dB of dynamic range. All data were obtained in a circular geometry. X-ray CT scans were used to generate X-ray images corresponding to the same 'slices' obtained with the ultrasound scanner. The good match of sensitivity, resolution and angular coverage between the ultrasound and X-ray data makes possible a direct comparison of the three types of images. We present the results of such a comparison for an excised breast fixed in formalin. The results are presented visually using various types of data fusion. A general correspondence between the sound speed, reflectivity and X-ray morphologies is found. The degree to which data fusion can help characterize tissue is assessed by examining the quantitative correlations between the ultrasound and X-ray images.

  9. Fibroadenoma of axillary ectopic breast tissue: A rare clinical entity

    Directory of Open Access Journals (Sweden)

    Sunder Goyal

    2014-01-01

    Full Text Available Supernumerary breast or polymastia is a well-documented anomaly of the breast and commonly presents along the embryonic milk line extending between the axilla and groin. Reported incidence of accessory breast is 0.4-6% in females. During 2 years period, we encountered only two cases out of twenty cases of axillary lumps. We present one case of fibroadenoma in ectopic breast tissue (EBT in axilla. Ectopic breast denotes breast tissue at more than two pectoral regions, which is mostly benign but at times can be malignant. EBT is at a greater risk of malignancy. Fibroadenoma of ectopic axillary breast tissue (EBT is quiet rare, but should always be kept in mind for differential diagnosis of an axillary mass.

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

    Science.gov (United States)

    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.

  11. Associations of erythrocyte ω-3 fatty acids with biomarkers of ω-3 fatty acids and inflammation in breast tissue.

    Science.gov (United States)

    Roy, Shuvro; Brasky, Theodore M; Belury, Martha A; Krishnan, Shiva; Cole, Rachel M; Marian, Catalin; Yee, Lisa D; Llanos, Adana A; Freudenheim, Jo L; Shields, Peter G

    2015-12-15

    There is increasing evidence that chronic inflammation is associated with increased breast cancer risk. Long-chain omega-3 polyunsaturated fatty acids (LCω-3PUFA) may reduce circulating biomarkers of inflammation; however associations of blood LCω-3PUFA with breast tissue LCω-3PUFA and breast tissue biomarkers of inflammation are not well understood. We conducted a cross-sectional analysis of breast tissue and blood samples from n = 85 women with no history of breast cancer, who underwent breast reduction surgery. Fatty acids of erythrocytes and undissected breast tissues were analyzed by gas chromatography; C-reactive protein (CRP), interleukin (IL)-6 and IL-8 in plasma and tissue were measured by ELISA. Multivariable-adjusted regression models were used to estimate associations between erythrocyte LCω-3PUFA and breast tissue biomarkers. Women in the highest erythrocyte LCω-3PUFA tertile had LCω-3PUFA concentrations in the breast 73% (95% CI: 31-128%; p trend PUFA were similar in magnitude. No significant association was found for the shorter ω-3 PUFA, α-linolenic acid. Although compatible with no association, women in the highest tertile of erythrocyte eicosapentaenoic acid had a nonsignificant 32% (95% CI: -23 to 62%) reduced breast tissue CRP. No correlation was observed between erythrocyte ω-3 PUFA and tissue IL-6 or IL-8 concentrations. Our findings provide evidence that erythrocyte ω-3 fatty acids are valid measures of breast tissue concentrations, and limited evidence that inverse associations from prospective epidemiologic studies of blood LCω-3PUFA and breast cancer risk may be partly explained by reductions in breast tissue inflammation; however, these findings require replication.

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

    Science.gov (United States)

    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.

  13. Third-harmonic generation imaging of breast tissue biopsies.

    Science.gov (United States)

    Lee, Woowon; Kabir, Mohammad M; Emmadi, Rajyasree; Toussaint, Kimani C

    2016-11-01

    We demonstrate for the first time the imaging of unstained breast tissue biopsies using third-harmonic generation (THG) microscopy. As a label-free imaging technique, THG microscopy is compared to phase contrast and polarized light microscopy which are standard imaging methods for breast tissues. A simple feature detection algorithm is applied to detect tumour-associated lymphocyte rich regions in unstained breast biopsy tissue and compared with corresponding regions identified by a pathologist from bright-field images of hematoxylin and eosin stained breast tissue. Our results suggest that THG imaging holds potential as a complementary technique for analysing breast tissue biopsies. © 2016 The Authors Journal of Microscopy © 2016 Royal Microscopical Society.

  14. "COMPARISON BETWEEN NUMBER OF NERVE FIBERS IN NORMAL BREAST TISSUE, BENIGN LESIONS AND MALIGNANT BREAST TUMORS"

    Directory of Open Access Journals (Sweden)

    H. Soltanghoraiee

    2004-10-01

    Full Text Available Breast cancer is common and is considered second cause of cancer related mortality in females. Regarding importance of breast cancer, more investigation in this field is recommended. For many years investigators believed that neoplasms were not innervated but new findings have proved otherwise. This descriptive study was carried out to compare number of nerve fibers in benign, malignant and normal breast tissue. Of each group several slides were reviewed and 3608.50 mm2 of malignant tumors (ductal carcinoma, 3641 mm2 of benign tumors (fibroadenoma and 2331.25 mm2 of normal breast tissue (mammoplasty were assessed. Numbers of nerve fibers were compared and a significant increase in nerve fibers was found in malignant tumors compared with benign tumors and normal breast tissue. Accuracy of hematoxylin and eosin method were examined by immunohistochemistry staining (neurofilament method and affirmed. These results reveal that malignant tumors of breast have more nerve fibers than normal breast tissue or benign tumors.

  15. Breast tissue and breast cancer risk in abnormal secernation

    Directory of Open Access Journals (Sweden)

    G. Kh. Khanafiev

    2014-01-01

    Full Text Available From 122 of women with aseptic discharge from breast milk glands in 42.6 % of the cases in history was celebrated mastitis or postpartum lactostasis (25.4 %. Study the contents of the bile ducts, the state of periductale tissue of mammary glands of these women showed that a high titer of bacterial invasion was typical for women in the age of 35–55 years as among parous (10.7 %, and in nulliparous (8.2 %. The proliferating epithelium in the ducts is more marked in women who have had an abortion (4.9 % and parous women of reproductive age (4.1 %. For сецернирующих of mammary glands is more characteristic of differentiation on the grounds of proliferation and autoimmunisacion. Cistic-advanced ducts, as a source of excessive hormone concentrations, leading to displastic processes of the walls of the cystic formations and periductale tissue, is an indication for the beginning of the immediate treatment of the patient.

  16. Infrared absorption of human breast tissues in vitro

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-07-15

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

  17. Functional Imaging of Breast Tissue and Clinical Application

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    A novel approach to image hemoglobin concentration(ΔDhb) and oxygen saturation (ΔDoxy) of breast tissue is presented. The scenograph of dual-wavelength (760 and 850 nm) near infrared lights through breast tissue is acquired by high sensitive charge coupled device (CCD) camera. The evaluation criterion of the difference of ΔDhb and ΔDoxy between detected and referenced breast tissue can be obtained by a calculation formula without complicate caculation. This approach is applied to clinic detection in breast tissue. The ongoing clinical experiments indicate that malignant tumor usually exhibits characterize of "higher ΔDhb and lower ΔDoxy", while benign lesion often shows "lower ΔDhb and higher ΔDoxy" or other characters. So it is useful to assist the diagnosis of breast disease.

  18. Regulation of Breast Cancer Stem Cells by Tissue Rigidity

    Science.gov (United States)

    2015-06-01

    alignment by second harmonic generation imaging (SHG) and used it as a surrogate marker for tissue rigidity. In agreement with previous publications6–8,44,45...AD ____________ __ Award Number: W81XWH-13-1-0133 TITLE: Regulation of Breast Cancer Stem Cells by Tissue Rigidity PRINCIPAL INVESTIGATOR: Adam J...CONTRACT NUMBER Regulation of Breast Cancer Stem Cell by Tissue Rigidity W81XWH-13-1-0133 Sb. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR

  19. Tissue specific DNA methylation in normal human breast epithelium and in breast cancer.

    Science.gov (United States)

    Avraham, Ayelet; Cho, Sean Soonweng; Uhlmann, Ronit; Polak, Mia Leonov; Sandbank, Judith; Karni, Tami; Pappo, Itzhak; Halperin, Ruvit; Vaknin, Zvi; Sella, Avishay; Sukumar, Saraswati; Evron, Ella

    2014-01-01

    Cancer is a heterogeneous and tissue-specific disease. Thus, the tissue of origin reflects on the natural history of the disease and dictates the therapeutic approach. It is suggested that tissue differentiation, mediated mostly by epigenetic modifications, could guide tissue-specific susceptibility and protective mechanisms against cancer. Here we studied breast specific methylation in purified normal epithelium and its reflection in breast cancers. We established genome wide methylation profiles of various normal epithelial tissues and identified 110 genes that were differentially methylated in normal breast epithelium. A number of these genes also showed methylation alterations in breast cancers. We elaborated on one of them, TRIM29 (ATDC), and showed that its promoter was hypo-methylated in normal breast epithelium and heavily methylated in other normal epithelial tissues. Moreover, in breast carcinomas methylation increased and expression decreased whereas the reverse was noted for multiple other carcinomas. Interestingly, TRIM29 regulation in breast tumors clustered according to the PAM50 classification. Thus, it was repressed in the estrogen receptor positive tumors, particularly in the more proliferative luminal B subtype. This goes in line with previous reports indicating tumor suppressive activity of TRIM29 in estrogen receptor positive luminal breast cells in contrast to oncogenic function in pancreatic and lung cancers. Overall, these findings emphasize the linkage between breast specific epigenetic regulation and tissue specificity of cancer.

  20. Spontaneous infarction of hyperplastic breast tissue: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Eun Young; Nam, Sang Yu; Choi, Hye Young; Hong, Min Ji [Dept. of Radiology, Gil Medical Center, Gachon University School of Medicine and Science, Incheon (Korea, Republic of)

    2015-09-15

    Spontaneous breast infarction is a very rare complication of fibroadenoma of the breast. We present an interesting case of a 33-year-old woman with spontaneous infarction of hyperplastic breast tissue related to pregnancy and lactation. Mammography showed an oval, circumscribed, fat-containing mass with microcalcifications. Ultrasonography revealed an oval, circumscribed mass with echogenic dots. Color Doppler imaging revealed presence of minimal vascularity at the periphery of the mass.

  1. Sugary, High-Fat Western Diet Tied to Denser Breast Tissue

    Science.gov (United States)

    ... High-Fat Western Diet Tied to Denser Breast Tissue Previous research has linked higher density to increased ... Western-style diet may develop more dense breast tissue, possibly increasing their risk for breast cancer, Spanish ...

  2. GLUT 5 is not over-expressed in breast cancer cells and patient breast cancer tissues.

    Directory of Open Access Journals (Sweden)

    Gayatri Gowrishankar

    Full Text Available F18 2-Fluoro 2-deoxyglucose (FDG has been the gold standard in positron emission tomography (PET oncologic imaging since its introduction into the clinics several years ago. Seeking to complement FDG in the diagnosis of breast cancer using radio labeled fructose based analogs, we investigated the expression of the chief fructose transporter-GLUT 5 in breast cancer cells and human tissues. Our results indicate that GLUT 5 is not over-expressed in breast cancer tissues as assessed by an extensive immunohistochemistry study. RT-PCR studies showed that the GLUT 5 mRNA was present at minimal amounts in breast cancer cell lines. Further knocking down the expression of GLUT 5 in breast cancer cells using RNA interference did not affect the fructose uptake in these cell lines. Taken together these results are consistent with GLUT 5 not being essential for fructose uptake in breast cancer cells and tissues.

  3. Tissue and serum sialidase levels in breast cancer.

    Science.gov (United States)

    Sönmez, H; Süer, S; Güngör, Z; Baloglu, H; Kökoglu, E

    1999-02-08

    Breast cancer is both one of the most common and one of the most treatable of all human malignancies. It has been suggested by various investigators that sialic acid increases in the sera of cancerous patients. In cancer patients, an increase in the levels of serum sialic acid may also be due to an increase in the activity of serum or tissue sialidase. The purpose of the present investigation was to determine whether the concentration of sialidase in serum and breast tissue could be used as a tumor marker in breast cancer. In this study; serum sialidase levels in 26 patient with breast cancer and 31 controls were found to be 77.04+/-25.07 U/l and 55.56+/-7.50 U/l, respectively. The mean tissue sialidase levels in 26 breast cancer patients and 13 controls were 39.76+/-17.03 U/g protein and 14.30+/-7.09 U/g protein, respectively. Serum and tissue sialidase levels in breast cancer were significantly higher than those found in the control group (P breast cancer patients were found to be 67.73+/-11.87 U/l and 33.41+/-12.17 U/g protein and 87.89+/-31.94 U/l and 47.17+/-19.30 U/g protein, respectively. Also we found a significant difference between the levels of serum and tissue sialidase in Grade I-II and III (P < 0.05).

  4. Methylation and Immunoexpression of p16(INK4a) Tumor Suppressor Gene in Primary Breast Cancer Tissue and Their Quantitative p16(INK4a) Hypermethylation in Plasma by Real-Time PCR.

    Science.gov (United States)

    Lee, Jae Jun; Ko, Eunkyung; Cho, Junhun; Park, Ha Young; Lee, Jeong Eon; Nam, Seok Jin; Kim, Duk-Hwan; Cho, Eun Yoon

    2012-12-01

    The p16(INK4a) gene methylation has been reported to be a major tumorigenic mechanism. We evaluated the methylation status of the p16(INK4a) genes in 231 invasive breast cancer and 90 intraductal carcinoma specimens using a methylation-specific polymerase chain reaction and p16 protein expression using immunohistochemistry. The quantity of cell-free methylated p16(INK4a) DNA in the plasma samples of 200 patients with invasive breast cancer was also examined using a fluorescence-based real-time polymerase chain reaction assay. The frequencies of p16(INK4a) methylation in invasive and intraductal tumors were 52.8% (122/231) and 57.8% (52/90), respectively. The p16 protein was overexpressed in 145 of the 231 invasive carcinomas (62.8%) and 63 of the 90 intraductal carcinomas (70%). High p16 expression in invasive carcinomas correlated significantly with a high histologic grade, a negative estrogen receptor and progesterone receptor status, p53 immunoreactivity and high Ki-67 expression with immunohistochemistry. In addition, the methylation index of p16(INK4a) was significantly higher in the cancer patients than the normal controls (pp16 immunoreactivity correlated with a loss of differentiation in breast carcinomas and high frequency of p16(INK4a) promoter methylation in both invasive and intraductal carcinomas, suggesting it may be involved in the pathogenesis of breast cancer.

  5. Tissue modeling schemes in low energy breast brachytherapy.

    Science.gov (United States)

    Afsharpour, Hossein; Landry, Guillaume; Reniers, Brigitte; Pignol, Jean-Philippe; Beaulieu, Luc; Verhaegen, Frank

    2011-11-21

    Breast tissue is heterogeneous and is mainly composed of glandular (G) and adipose (A) tissues. The proportion of G versus A varies considerably among the population. The absorbed dose distributions in accelerated partial breast irradiation therapy with low energy photon brachytherapy sources are very sensitive to tissue heterogeneities. Current clinical algorithms use the recommendations of the AAPM TG43 report which approximates the human tissues by unit density water. The aim of this study is to investigate various breast tissue modeling schemes for low energy brachytherapy. A special case of breast permanent seed implant is considered here. Six modeling schemes are considered. Uniform and non-uniform water breast (UWB and NUWB) consider the density but neglect the effect of the composition of tissues. The uniform and the non-uniform G/A breast (UGAB and NUGAB) as well the age-dependent breast (ADB) models consider the effect of the composition. The segmented breast tissue (SBT) method uses a density threshold to distinguish between G and A tissues. The PTV D(90) metric is used for the analysis and is based on the dose to water (D(90(w,m))). D(90(m,m)) is also reported for comparison to D(90(w,m)). The two-month post-implant D(90(w,m)) averaged over 38 patients is smaller in NUWB than in UWB by about 4.6% on average (ranging from 5% to 13%). Large average differences of G/A breast models with TG43 (17% and 26% in UGAB and NUGAB, respectively) show that the effect of the chemical composition dominates the effect of the density on dose distributions. D(90(w,m)) is 12% larger in SBT than in TG43 when averaged. These differences can be as low as 4% or as high as 20% when the individual patients are considered. The high sensitivity of dosimetry on the modeling scheme argues in favor of an agreement on a standard tissue modeling approach to be used in low energy breast brachytherapy. SBT appears to generate the most geometrically reliable breast tissue models in this

  6. Implementation of several mathematical algorithms to breast tissue density classification

    Science.gov (United States)

    Quintana, C.; Redondo, M.; Tirao, G.

    2014-02-01

    The accuracy of mammographic abnormality detection methods is strongly dependent on breast tissue characteristics, where a dense breast tissue can hide lesions causing cancer to be detected at later stages. In addition, breast tissue density is widely accepted to be an important risk indicator for the development of breast cancer. This paper presents the implementation and the performance of different mathematical algorithms designed to standardize the categorization of mammographic images, according to the American College of Radiology classifications. These mathematical techniques are based on intrinsic properties calculations and on comparison with an ideal homogeneous image (joint entropy, mutual information, normalized cross correlation and index Q) as categorization parameters. The algorithms evaluation was performed on 100 cases of the mammographic data sets provided by the Ministerio de Salud de la Provincia de Córdoba, Argentina—Programa de Prevención del Cáncer de Mama (Department of Public Health, Córdoba, Argentina, Breast Cancer Prevention Program). The obtained breast classifications were compared with the expert medical diagnostics, showing a good performance. The implemented algorithms revealed a high potentiality to classify breasts into tissue density categories.

  7. The aluminium content of breast tissue taken from women with breast cancer.

    Science.gov (United States)

    House, Emily; Polwart, Anthony; Darbre, Philippa; Barr, Lester; Metaxas, George; Exley, Christopher

    2013-10-01

    The aetiology of breast cancer is multifactorial. While there are known genetic predispositions to the disease it is probable that environmental factors are also involved. Recent research has demonstrated a regionally specific distribution of aluminium in breast tissue mastectomies while other work has suggested mechanisms whereby breast tissue aluminium might contribute towards the aetiology of breast cancer. We have looked to develop microwave digestion combined with a new form of graphite furnace atomic absorption spectrometry as a precise, accurate and reproducible method for the measurement of aluminium in breast tissue biopsies. We have used this method to test the thesis that there is a regional distribution of aluminium across the breast in women with breast cancer. Microwave digestion of whole breast tissue samples resulted in clear homogenous digests perfectly suitable for the determination of aluminium by graphite furnace atomic absorption spectrometry. The instrument detection limit for the method was 0.48 μg/L. Method blanks were used to estimate background levels of contamination of 14.80 μg/L. The mean concentration of aluminium across all tissues was 0.39 μg Al/g tissue dry wt. There were no statistically significant regionally specific differences in the content of aluminium. We have developed a robust method for the precise and accurate measurement of aluminium in human breast tissue. There are very few such data currently available in the scientific literature and they will add substantially to our understanding of any putative role of aluminium in breast cancer. While we did not observe any statistically significant differences in aluminium content across the breast it has to be emphasised that herein we measured whole breast tissue and not defatted tissue where such a distribution was previously noted. We are very confident that the method developed herein could now be used to provide accurate and reproducible data on the aluminium content

  8. Fundamentals of gas phase plasmas for treatment of human tissue.

    Science.gov (United States)

    Kushner, Mark J; Babaeva, Natalia Yu

    2011-01-01

    The use of gas phase plasmas for treating human tissue is at the intersection of two disciplines - plasma physics and engineering, and medicine. In this paper, a primer will be provided for the medical practitioner on the fundamentals of generating gas phase plasmas at atmospheric pressure in air for the treatment of human tissue. The mechanisms for gas phase plasmas interacting with tissue and biological fluids will also be discussed using results from computer modeling.

  9. Prolactin as an autocrine/paracrine factor in breast tissue.

    Science.gov (United States)

    Clevenger, C V; Plank, T L

    1997-01-01

    The neuroendocrine hormone prolactin (PRL) stimulates breast growth and differentiation during puberty, pregnancy, and lactation. Despite extensive and convincing data indicating that PRL significantly contributes to the pathogenesis and progression of rodent mammary carcinoma, parallel observations for human breast cancer have not been concordant. In particular, the therapeutic alteration of somatolactogenic hormone levels has not consistently altered the course of human breast cancer. Recent data, however, suggest that extra-pituitary tissues are capable of elaborating PRL; indeed, the observation of sustained serum levels of PRL in post-hypophysectomy patients supports this hypothesis. Proof of an autocrine/paracrine loop for PRL within normal and malignant human breast tissues requires that the following three criteria be met: (1) PRL must be synthesized and secreted within mammary tissues; (2) the receptor for PRL (PRLR) must be present within these tissues; and, (3) proliferative responses to autocrine/paracrine PRL must be demonstrated. These criteria have now been fulfilled in several laboratories. With the demonstration of a PRL autocrine/paracrine loop in mammary glands, the basis for the ineffective treatment of human breast cancer by prior endocrine-based anti-somatolactogenic therapies is evident. These findings provide the precedent for novel therapeutic strategies aimed at interrupting the stimulation of breast cancer growth by PRL at both endocrine and autocrine/paracrine levels.

  10. A Breast Tissue Protein Expression Profile Contributing to Early Parity-Induced Protection Against Breast Cancer

    Directory of Open Access Journals (Sweden)

    Christina Marie Gutierrez

    2015-11-01

    Full Text Available Background/Aims: Early parity reduces breast cancer risk, whereas, late parity and nulliparity increase breast cancer risk. Despite substantial efforts to understand the protective effects of early parity, the precise molecular circuitry responsible for these changes is not yet fully defined. Methods: Here, we have conducted the first study assessing protein expression profiles in normal breast tissue of healthy early parous, late parous, and nulliparous women. Breast tissue biopsies were obtained from 132 healthy parous and nulliparous volunteers. These samples were subjected to global protein expression profiling and immunohistochemistry. GeneSpring and MetaCore bioinformatics analysis software were used to identify protein expression profiles associated with early parity (low risk versus late/nulliparity (high risk. Results: Early parity reduces expression of key proteins involved in mitogenic signaling pathways in breast tissue through down regulation of EGFR1/3, ESR1, AKT1, ATF, Fos, and SRC. Early parity is also characterized by greater genomic stability and reduced tissue inflammation based on differential expression of aurora kinases, p53, RAD52, BRCA1, MAPKAPK-2, ATF-1, ICAM1, and NF-kappaB compared to late and nulli parity. Conclusions: Early parity reduces basal cell proliferation in breast tissue, which translates to enhanced genomic stability, reduced cellular stress/inflammation, and thus reduced breast cancer risk.

  11. Development, fabrication and evaluation of a novel biomimetic human breast tissue derived breast implant surface.

    Science.gov (United States)

    Barr, S; Hill, E W; Bayat, A

    2017-02-01

    Breast implant use has tripled in the last decade with over 320,000 breast implant based reconstructions and augmentations performed in the US per annum. Unfortunately a considerable number of women will experience capsular contracture, the irrepressible and disfiguring, tightening and hardening of the fibrous capsule that envelops the implant. Functionalising implant surfaces with biocompatible tissue-specific textures may improve in vivo performance. A novel biomimetic breast implant is presented here with anti-inflammatory in vitro abilities. Topographical assessment of native breast tissue facilitated the development of a statistical model of adipose tissue. 3D grayscale photolithography and ion etching were combined to successfully replicate a surface modelled upon the statistics of breast tissue. Pro-inflammatory genes ILβ1, TNFα, and IL6 were downregulated (p<0.001) and anti-inflammatory gene IL-10 were upregulated on the novel surface. Pro-inflammatory cytokines Gro-Alpha, TNFα and neutrophil chemoattractant IL8 were produced in lower quantities and anti-inflammatory IL-10 in higher quantities in culture with the novel surface (p<0.01). Immunocytochemistry and SEM demonstrated favourable fibroblast and macrophage responses to these novel surfaces. This study describes the first biomimetic breast tissue derived breast implant surface. Our findings attest to its potential translational ability to reduce the inflammatory phase of the implant driven foreign body reaction.

  12. Characterization of breast tissue composition and breast cancer risk assessment using non-invasive transillumination breast spectroscopy (TIBS)

    Science.gov (United States)

    Blackmore, Kristina M.; Weersink, Robert; Lilge, Lothar

    2005-09-01

    Tissue undergoing transformation into a state that is more favourable for tumor growth may present itself with different tissue optical properties and contain different amounts of the major tissue chromophores. Here, we decomposed transillumination spectra obtain in women from various risk levels of developing breast cancer.

  13. Expression Quantitative Trait loci (QTL) in tumor adjacent normal breast tissue and breast tumor tissue

    Science.gov (United States)

    Quiroz-Zárate, Alejandro; Harshfield, Benjamin J.; Hu, Rong; Knoblauch, Nick; Beck, Andrew H.; Hankinson, Susan E.; Carey, Vincent; Tamimi, Rulla M.; Hunter, David J.; Quackenbush, John; Hazra, Aditi

    2017-01-01

    We investigate 71 single nucleotide polymorphisms (SNPs) identified in meta-analytic studies of genome-wide association studies (GWAS) of breast cancer, the majority of which are located in intergenic or intronic regions. To explore regulatory impacts of these variants we conducted expression quantitative loci (eQTL) analyses on tissue samples from 376 invasive postmenopausal breast cancer cases in the Nurses’ Health Study (NHS) diagnosed from 1990–2004. Expression analysis was conducted on all formalin-fixed paraffin-embedded (FFPE) tissue samples (and on 264 adjacent normal samples) using the Affymetrix Human Transcriptome Array. Significance and ranking of associations between tumor receptor status and expression variation was preserved between NHS FFPE and TCGA fresh-frozen sample sets (Spearman r = 0.85, p<10^-10 for 17 of the 21 Oncotype DX recurrence signature genes). At an FDR threshold of 10%, we identified 27 trans-eQTLs associated with expression variation in 217 distinct genes. SNP-gene associations can be explored using an open-source interactive browser distributed in a Bioconductor package. Using a new a procedure for testing hypotheses relating SNP content to expression patterns in gene sets, defined as molecular function pathways, we find that loci on 6q14 and 6q25 affect various gene sets and molecular pathways (FDR < 10%). Although the ultimate biological interpretation of the GWAS-identified variants remains to be uncovered, this study validates the utility of expression analysis of this FFPE expression set for more detailed integrative analyses. PMID:28152060

  14. Evaluation of magnetization transfer ratios for breast tissues and breast diseases

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Fumio; Murai, Hiroshi; Takeuchi, Thouru; Iwase, Takuji; Miura, Shigeto; Mastushima, Shigeru; Oosaki, Hikaru [Aichi Cancer Center, Nagoya (Japan). Hospital; Kinosada, Yasuomi

    1997-03-01

    To determine MTRs for normal structures and benign diseases in the breast two-dimensional magnetization transfer imaging was performed in 62 patients and in 3 young female volunteers. With regard to the MTRs of measurements in the normal breast tissues, fat tissues which is close to simple cysts in MTRs show little transfer of longitudinal magnetization. MTRs of the muscles was 15.15{+-}6.22%, which exceeded those of breast parenchyma. The breast parenchyma didn`t show the change of MTR value due to the difference of patient age and due to variable amount of fat and fibrous tissues. Breast parenchyma in the two young volunteers clearly showed biphasic change of MTR values in accordance with the menstrual cycle; little transfer value was due to hydration in the postovulatory period and high transfer value was due to dehydration in the preovulatory period. In the remaining one volunteer during lactation period, mammary parenchyma shows sever decrease in MTR, because mammary gland is loaded with massive fluid, showing a very high signal intensity on First IR and T2-weighted images. MTR values of benign breast diseases including mastopathy, fibroadenoma and phyllodes tumor had no significant difference from those of the breast parenchyma and muscle. Non-invasive ductal carcinoma was equivalent to breast parenchyma in MTR. (K.H.)

  15. EXPRESSION AND CLINICAL SIGNIFICANCE OF p73A IN BREAST CARCINOMA TISSUES

    Institute of Scientific and Technical Information of China (English)

    ZHOU Xin; SUN Zhi-jun

    2005-01-01

    Objective: To study the expression and clinical significance of p73( in breast carcinomas. Methods: The expression of p73( was detected by immunohistochemistry in 41 breast carcinoma tissues, 13 benign breast tumor tissues and 8 normal tissues and 8 normal breast tissues, respectively. Results: The positive expression of p73( was found in 20/41 (48.8%) of breast carcinoma tissues, 1/13 (7.7%) of benign breast tumor tissues. The positive expression rate of p73( in breast carcinoma tissues was significant1y higher than that in benign breast tumor tissues and normal breast tissues (P<0.05). The expression intensity of p73( increased significantly in breast carcinoma tissues compared with benign breast tumor tissues and normal breast tissues (P<0.05). Significant association of the expression of p73( with lymph node metastases and TNM stages of the carcinoma was found (P<0.05). The expression of p73( displayed a positive correlation with p53 (P<0.05). Conclusion: These results suggest that there is an up-regulation of p73( expression in breast carcinoma tissues, which may be implicated in the tumorigenesis of breast carcinoma as a molecular alteration.

  16. Infrared microspectroscopic imaging of benign breast tumor tissue sections

    Science.gov (United States)

    Fabian, H.; Lasch, P.; Boese, M.; Haensch, W.

    2003-12-01

    We have applied infrared microspectroscopic imaging for the examination of benign breast tumor tissue sections. The IR spectra of the sections were obtained by classical point microscopy with a movable stage and via a microscope equipped with a focal plane array detector. The infrared microscopic data were analysed using functional group mapping techniques and cluster analysis. The output values of the two procedures were reassembled into infrared images of the tissues, and were compared with standard staining images of the corresponding tissue region. The comparative examination of identical tissue sections by the two IR approaches enabled us to assess potential problems associated with tissue microheterogeneity. It was found that in case of fibroadenoma, a benign lesion located in breast ducts, point microscopy with a spot size of ˜30 μm is a useful practical approach which minimizes the possibility of 'contamination' of the spectra because of spectral averaging of all tissue components present in the corresponding microareas. A comparison of the spectra of the benign breast tumor with those of a malignant ductal carcinoma in situ revealed that IR microspectroscopy has the potential to differentiate between these two breast tumor types.

  17. Method for breast cancer diagnosis by phase spectrophotometry of human blood plasma

    Science.gov (United States)

    Mintser, Ozar P.; Oliinychenko, B. P.

    2012-01-01

    The possibility of breast cancer diagnostics by means of phase structure measurements of laser radiation transformed by human blood plasma samples. The theoretical fundamentals of polarization filtration method for direct phase shifts measurements of microscopic images are provided. The optical model of polycrystalline networks of blood plasma proteins is suggested. The results of investigating the interrelation between the values of statistical (statistical moments of the 1st-4th order), correlation (correlation area, asymmetry coefficient and autocorrelation function excess) and fractal (dispersion of logarithmic dependencies of power spectra) parameters are presented. They characterize the coordinate distributions of phase shifts between the orthogonal components of the amplitude in the points of laser images of blood plasma smears and pathological changes in the mammary gland tissue. The diagnostic criteria of breast cancer nascency are determined.

  18. Residual Breast Tissue after Mastectomy : How Often and Where Is It Located?

    NARCIS (Netherlands)

    Griepsma, M.; van Zuidewijn, D. B. W. de Roy; Grond, A. J. K.; Siesling, S.; Groen, H.; de Bock, G. H.

    Background. Residual breast tissue after a mastectomy can lead to a (second) primary breast cancer. The development of breast cancer after prophylactic mastectomy and the finding of normal breast tissue around a local recurrence support this assumption. The aim of the present study was to

  19. Residual breast tissue after mastectomy: how often and where is it located?

    NARCIS (Netherlands)

    Griepsma, M.; de Roy van Zuidewijn, D.B.W.; Grond, A.J.K.; Siesling, Sabine; Groen, H.; de Bock, G.H.

    2014-01-01

    Background Residual breast tissue after a mastectomy can lead to a (second) primary breast cancer. The development of breast cancer after prophylactic mastectomy and the finding of normal breast tissue around a local recurrence support this assumption. The aim of the present study was to investigate

  20. Residual Breast Tissue after Mastectomy : How Often and Where Is It Located?

    NARCIS (Netherlands)

    Griepsma, M.; van Zuidewijn, D. B. W. de Roy; Grond, A. J. K.; Siesling, S.; Groen, H.; de Bock, G. H.

    2014-01-01

    Background. Residual breast tissue after a mastectomy can lead to a (second) primary breast cancer. The development of breast cancer after prophylactic mastectomy and the finding of normal breast tissue around a local recurrence support this assumption. The aim of the present study was to investigat

  1. Residual breast tissue after mastectomy: how often and where is it located?

    NARCIS (Netherlands)

    Griepsma, M.; Roy van Zuidewijn, de D.B.W.; Grond, A.J.K.; Siesling, S.; Groen, H.; Bock, de G.H.

    2014-01-01

    Background Residual breast tissue after a mastectomy can lead to a (second) primary breast cancer. The development of breast cancer after prophylactic mastectomy and the finding of normal breast tissue around a local recurrence support this assumption. The aim of the present study was to investigate

  2. Tissue inhibitor of metalloproteinases-1 in breast cancer

    DEFF Research Database (Denmark)

    Würtz, Sidse Ørnbjerg; Rasmussen, Anne-Sofie Schrohl; Sørensen, Nanna Møller

    2005-01-01

    biological functions of TIMP-1 such as growth-stimulating functions, as well as anti-apoptotic and pro-angiogenetic effects, may in part explain this paradox. The purpose of this review is to give an update on the current status of TIMP-1 in breast cancer, emphasizing the prognostic utility of the inhibitor......Whether patients diagnosed with primary breast cancer are offered adjuvant systemic therapy following surgical removal of the tumor is based on prognosis. Prognosis is estimated in every patient using established prognostic variables. Unfortunately, when using the currently available prognostic...... parameters a significant proportion of patients are over-treated. Thus, in order to improve stratification of breast cancer patients, additional prognostic factors need to be identified. Tissue inhibitor of metalloproteinases-1 (TIMP-1) is one of the promising candidates for new prognostic markers in breast...

  3. Plasma protein carbonyl levels and breast cancer risk.

    Science.gov (United States)

    Rossner, Pavel; Terry, Mary Beth; Gammon, Marilie D; Agrawal, Meenakshi; Zhang, Fang Fang; Ferris, Jennifer S; Teitelbaum, Susan L; Eng, Sybil M; Gaudet, Mia M; Neugut, Alfred I; Santella, Regina M

    2007-01-01

    To study the role of oxidative stress in breast cancer risk, we analysed plasma levels of protein carbonyls in 1050 cases and 1107 controls. We found a statistically significant trend in breast cancer risk in relation to increasing quartiles of plasma protein carbonyl levels (OR = 1.2, 95% CI = 0.9-1.5; OR = 1.5, 95% CI = 1.2-2.0; OR = 1.6, 95% CI = 1.2-2.1, for the 2(nd), 3(rd) and 4(th) quartile relative to the lowest quartile, respectively, P for trend = 0.0001). The increase in risk was similar for younger ( or = 15 grams/day for 4(th) quartile versus lowest quartile OR = 2.3, 95% CI = 1.1-4.7), and hormone replacement therapy use (HRT, OR = 2.6, 95% CI = 1.6-4.4 for 4(th) quartile versus lowest quartile). The multiplicative interaction terms were statistically significant only for physical activity and HRT. The positive association between plasma protein carbonyl levels and breast cancer risk was also observed when the analysis was restricted to women who had not received chemotherapy or radiation therapy prior to blood collection. Among controls, oxidized protein levels significantly increased with cigarette smoking and higher fruit and vegetable consumption, and decreased with alcohol consumption >30 grams per day. Women with higher levels of plasma protein carbonyl and urinary 15F(2t)-isoprostane had an 80% increase in breast cancer risk (OR = 1.8, 95% CI = 1.2-2.6) compared to women with levels below the median for both markers of oxidative stress. In summary, our results suggest that increased plasma protein carbonyl levels may be associated with breast cancer risk.

  4. Increasing in activity and plasma concentration of matrix metalloproteinase-9 in metastatic breast cancer patients

    Directory of Open Access Journals (Sweden)

    Morteza Sadeghi1

    2009-01-01

    patients and also, for diagnosis of susceptible breast cancer women for metastasis to other tissues.Conclusion: The present data suggest that the concentration of active MMP-9 in breast cancer patients has a significant increasing comparison with the control group and the increasing in plasma level of this enzyme is related with the existence of T allele at this gene promoter and also progression of breast cancer in this persons, we can use the active plasma level of this enzyme or the existence of T allele as a diagnostic value for discriminating subgroups of breast cancer patients and diagnosis of susceptible breast cancer women for metastasis to the other tissues. J Mazand Univ Med Sci 2009; 19(71: (Persian

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

    Science.gov (United States)

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

    2007-01-01

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

  6. Differential effects of progestins on breast tissue enzymes.

    Science.gov (United States)

    Pasqualini, J R

    2003-12-10

    There is substantial evidence that mammary cancer tissue contains all the enzymes responsible for the local biosynthesis of estradiol (E2) from circulating precursors. Two principal pathways are implicated in the final steps of E2 formation in breast cancer tissue: the 'aromatase pathway' that transforms androgens into estrogens and the 'sulfatase pathway' that converts estrone sulfate (E1S) into estrone (E1) via estrone sulfatase. The final step is the conversion of weak E1 to potent biologically active E2 via reductive 17beta-hydroxysteroid dehydrogenase type 1 activity. It is also well established that steroid sulfotransferases, which convert estrogens into their sulfates, are present in breast cancer tissues. One of the possible means of blocking E2 effects in breast cancer is to use anti-estrogens, which act by binding to the estrogen receptor (ER). Another option is to block E2 using anti-enzymes (anti-sulfatase, anti-aromatase, or anti-17beta-hydroxysteroid dehydrogenase (17beta-HSD). Various progestins (e.g. promegestone, nomegestrol acetate, medrogestone, 17-deacetyl norgestimate, dydrogesterone and its 20-dihydro derivative), as well as tibolone and its metabolites, have been shown to inhibit estrone sulfatase and 17beta-hydroxysteroid dehydrogenase. Some progestins and tibolone can also stimulate sulfotransferase activity. These various progestins may therefore provide a new option for the treatment of breast cancer.

  7. Tissue inhibitor of metalloproteinases-1 in breast cancer

    DEFF Research Database (Denmark)

    Würtz, Sidse Ørnbjerg; Rasmussen, Anne-Sofie Schrohl; Sørensen, Nanna Møller

    2005-01-01

    parameters a significant proportion of patients are over-treated. Thus, in order to improve stratification of breast cancer patients, additional prognostic factors need to be identified. Tissue inhibitor of metalloproteinases-1 (TIMP-1) is one of the promising candidates for new prognostic markers in breast...... is inhibition of the activity of various matrix metalloproteinases (MMPs). The association between high levels of protease inhibitor and poor prognosis may be somewhat surprising, as proteolytic activity plays a pivotal role in cancer cell invasion and metastasis. However, the recent discovery of other...

  8. Tissue Expander Capsule for Abdominal Wall in Autologous Breast Reconstruction

    Directory of Open Access Journals (Sweden)

    Ronaldo Scholze Webster, MD, PhD

    2014-11-01

    Full Text Available Summary: Adjuvant treatment planning can change after breast cancer resection and definitive pathological examination. Radiation therapy is often chosen as a supplementary treatment. Rectus abdominis–based muscle flaps are one of the main choices when breast reconstruction plans must be changed from implant-based to autologous methods. We herein report a case in which the patient’s own tissue expander capsule was used to repair an abdominal wall defect after muscle-sparing transverse rectus abdominis myocutaneous flap reconstruction.

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

    Science.gov (United States)

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

    2015-09-01

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

  10. FT-Raman spectroscopy study of human breast tissue

    Science.gov (United States)

    Bitar Carter, Renata A.; Martin, Airton A.; Netto, Mario M.; Soares, Fernando A.

    2004-07-01

    Optical spectroscopy has been extensively studied as a potential in vivo diagnostic tool to provide information about the chemical and morphologic structure of tissue. Raman Spectroscpy is an inelastic scattering process that can provide a wealth of spectral features that can be related to the specific molecular structure of the sample. This article reports results of an in vitro study of the FT-Raman human breast tissue spectra. An Nd:YAG laser at 1064nm was used as the excitation source in the FT-Raman Spectrometer. The neoplastic human breast samples, both Fibroadenoma and ICD, were obtained during therapeutical routine medical procedures required by the primary disease, and the non-diseased human tissue was obtained in plastic surgery. No sample preparation was needed for the FT-Raman spectra collection. The FT-Raman spectra were recorded from normal, benign (Fibroadenomas) and malignant (IDC-Intraductal Carcinoma) samples, adding up 51 different areas. The main spectral differences of a typical FT-Raman spectra of a Normal (Non-diseased), Fibroadenoma, and Infiltrating Ductal Carcinoma (IDC) breast tissue at the interval of 600 to 1800cm-1, which may differentiate diagnostically the sample, were found in the bands of 1230 to 1295cm-1, 1440 to 1460 cm-1 and 1650 to 1680 cm-1, assigned to the vibrational bands of the carbohydrate-amide III, proteins and lipids, and carbohydrate-amide I, respectively.

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

    Science.gov (United States)

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

    2012-08-01

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

  12. Breast image pre-processing for mammographic tissue segmentation.

    Science.gov (United States)

    He, Wenda; Hogg, Peter; Juette, Arne; Denton, Erika R E; Zwiggelaar, Reyer

    2015-12-01

    During mammographic image acquisition, a compression paddle is used to even the breast thickness in order to obtain optimal image quality. Clinical observation has indicated that some mammograms may exhibit abrupt intensity change and low visibility of tissue structures in the breast peripheral areas. Such appearance discrepancies can affect image interpretation and may not be desirable for computer aided mammography, leading to incorrect diagnosis and/or detection which can have a negative impact on sensitivity and specificity of screening mammography. This paper describes a novel mammographic image pre-processing method to improve image quality for analysis. An image selection process is incorporated to better target problematic images. The processed images show improved mammographic appearances not only in the breast periphery but also across the mammograms. Mammographic segmentation and risk/density classification were performed to facilitate a quantitative and qualitative evaluation. When using the processed images, the results indicated more anatomically correct segmentation in tissue specific areas, and subsequently better classification accuracies were achieved. Visual assessments were conducted in a clinical environment to determine the quality of the processed images and the resultant segmentation. The developed method has shown promising results. It is expected to be useful in early breast cancer detection, risk-stratified screening, and aiding radiologists in the process of decision making prior to surgery and/or treatment.

  13. Cost analysis of near-infrared spectroscopy tissue oximetry for monitoring autologous free tissue breast reconstruction.

    Science.gov (United States)

    Pelletier, Aaron; Tseng, Charles; Agarwal, Shailesh; Park, Julie; Song, David

    2011-10-01

    Free flap monitoring typically requires specialized nursing that can increase medical costs. This study uses near-infrared spectroscopy (NIRS) tissue oximetry to monitor free tissue breast reconstruction. We hypothesize this practice will reduce medical costs by eliminating the need for specialized nursing. From August 2006 to January 2010, women undergoing unilateral free tissue breast reconstruction were enrolled and admitted postoperatively to either the surgical intensive care unit (ICU) or floor. Each underwent continuous monitoring using NIRS tissue oximetry and intermittent clinical examination with surface Doppler ultrasonography. Patient demographics, comorbidities, perioperative details, and financial data were recorded. There were 50 patients studied, all with abdominal-based flaps (25 per group). There were no statistically significant differences in patient demographics, comorbidities, mean flap weight, ischemia time, or length of stay between the ICU and floor groups. Four flaps had vascular complications, all detected by NIRS tissue oximetry. Comparison of hospital costs showed an average reduction of $1937 per patient when monitored on the surgical floor (P = 0.036). NIRS tissue oximetry is a sensitive and reliable monitoring tool, eliminating the need for specialized nursing care. The effect is decreased cost structure and increased hospital contribution margin for autologous free tissue breast reconstruction.

  14. Experimental research on plasma destruction of bone tissue

    Directory of Open Access Journals (Sweden)

    Vdovin O.V.

    2012-06-01

    Full Text Available The main condition in achieving a favorable outcome is surgical treatment of patients with tumor-like diseases and benign bone tumors erosion of neoplasm within the healthy tissues. To reduce the number of recurrences the various chemical and physical methods on resection areas have been performed. The authors have proposed a new method of low temperature plasma treatment of bone tissue with the temperature of 20000°C. Exposing the plasma flow on bone tissue leads to loss of all cellular elements including neoplastic elements with preservation of the mineral bone structure. The direct correlation between the capacity of the plasma flow and intensity of bone destruction has been defined. This allows a differentiated use of plasma destruction in skeletal bones according to anatomy, size and type of bone tissue (spongy or cortical as well as patient's individual condition of the tissue

  15. Regulation of Breast Cancer Stem Cell by Tissue Rigidity

    Science.gov (United States)

    2015-06-01

    Gilman Drive, La Jolla, California 92093-0819, USA. 7Present address: Department of Immunology , The University of Texas MD Anderson Cancer Center, 7455...AD_________________ Award Number: W81XWH-13-1-0132 TITLE: Regulation of Breast Cancer Stem Cell by Tissue Rigidity PRINCIPAL INVESTIGATOR: Jing...for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of

  16. A rare presentation of an ectopic breast tissue in axilla

    Directory of Open Access Journals (Sweden)

    Radhika Vidyasagar

    2015-10-01

    Full Text Available Accessory breast tissue is rare accounting to less than 1% cases seen in females. It is usually bilateral. We report a case of 24-year-old woman with a lump in the left axilla in view of its rarity and made a differential diagnosis of fibroadenoma, which following the investigations and histopathological report was confirmed as revealed fibroadenoma in the axilla. It should also be considered as a differential diagnosis for all axillary swellings.

  17. The Linkage between Breast Cancer, Hypoxia, and Adipose Tissue.

    Science.gov (United States)

    Rausch, Linda K; Netzer, Nikolaus C; Hoegel, Josef; Pramsohler, Stephan

    2017-01-01

    The development of breast cancer cells is linked to hypoxia. The hypoxia-induced factor HIF-1α influences metastasis through neovascularization. Hypoxia seems to decrease the responsiveness to hormonal treatment due to loss of estrogen receptors (ERs). Obesity is discussed to increase hypoxia in adipocytes, which promotes a favorable environment for tumor cells in mammary fat tissue, whereas, tumor cells profit from good oxygen supply and are influenced by its deprivation as target regions within tumors show. This review gives an overview of the current state on research of hypoxia and breast cancer in human adipose tissue. A systematic literature search was conducted on PubMed (2000-2016) by applying hypoxia and/or adipocytes and breast cancer as keywords. Review articles were excluded as well as languages other than English or German. There was no restriction regarding the study design or type of breast cancer. A total of 35 papers were found. Eight studies were excluded due to missing at least two of the three keywords. One paper was removed due to Russian language, and one was dismissed due to lack of adherence. Seven papers were identified as reviews. After applying exclusion criteria, 18 articles were eligible for inclusion. Two articles describe the impairment of mammary epithelial cell polarization through hypoxic preconditioning. A high amount of adipocytes enhances cancer progression due to the increased expression of HIF-1α which causes the loss of ER α protein as stated in four articles. Four articles analyzed that increased activation of HIF's induces a series of transcriptions resulting in tumor angiogenesis. HIF inhibition, especially when combined with cytotoxic chemotherapy, holds strong potential for tumor suppression as stated in further four articles. In two articles there is evidence of a strong connection between hypoxia, oxidative stress and a poor prognosis for breast cancer via HIF regulated pathways. Acute hypoxia seems to normalize the

  18. Plasma DNA integrity index as a potential molecular diagnostic marker for breast cancer.

    Science.gov (United States)

    Kamel, Azza M; Teama, Salwa; Fawzy, Amal; El Deftar, Mervat

    2016-06-01

    Plasma DNA integrity index is increased in various malignancies including breast cancer, the most common cancer in women worldwide; early detection is crucial for successful treatment. Current screening methods fail to detect many cases of breast cancer at an early stage. In this study, we evaluated the level of plasma DNA integrity index in 260 females (95 with breast cancer, 95 with benign breast lesions, and 70 healthy controls) to verify its potential value in discriminating malignant from benign breast lesions. The criteria of the American Joint Committee on Cancer were used for staging of breast cancer patients. DNA integrity index was measured by real-time PCR. DNA integrity index was significantly higher in breast cancer than in benign breast patients and healthy subjects (P = cancer group was 85.3 % at 0.55 DNA integrity index cutoff. In conclusion, the plasma DNA integrity index may be a promising molecular diagnostic marker of malignancy in breast lesions.

  19. Comparative Proteome Analysis of Breast Cancer and Adjacent Normal Breast Tissues in Human

    Institute of Scientific and Technical Information of China (English)

    Shi-Shan Deng; Tian-Yong Xing; Hong-Ying Zhou; Ruo-Hong Xiong; You-Guang Lu; Bin Wen; Shang-Qing Liu; Hui-Jun Yang

    2006-01-01

    Two-dimensional polyacryiamide gel electrophoresis (2D-PAGE) and matrixassisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS), incorporated with online database searching, were performed to investigate differential proteins of breast cancer and adjacent normal breast tissues. Considering that serum albumin is abundantly presented in normal control samples, 15 differential spots detected in 11 out of 12 (91.7%) breast cancer samples were identified by online SIENA-2DPAGE database searching and MALDI-TOF/TOF-MS analysis. The results indicate that pathological changes of breast cancer are concerned with augmentation of substance metabolism, promotion of proteolytic activity, decline of activity of some inhibitors of enzymes, and so on. Some important proteins involved in the pathological process of breast cancer with changed expression may be useful biomarkers, such as alpha-1-antitrypsin, EF1-beta, cathepsin D, TCTP, SMT3A, RPS12, and PSMA1, among which SMT3A,RPS12, and PSMA1 were first reported for breast cancer in this study.

  20. Varied presentations of ectopic breast - polymastia, fibroadenoma, and carcinoma arising from ectopic breast tissue

    Directory of Open Access Journals (Sweden)

    Yasmeen Khatib

    2015-01-01

    Full Text Available Ectopic breast is a congenital anomaly of the breast which can have varied presentations because of its different sites and pathologies arising from it. Lesions of ectopic breast tissue (EBT are commonly seen due to persistence of embryonic remnants along the milk line. They have also been reported from other sites like face, vulva, and perineum. They are prone to the same physiological and pathological alterations seen in the normal breast. Only 0.3% of breast carcinomas arise in the ectopic breast, whereas only a few cases of fibroadenoma have been reported at this site. We present a case of polymastia in a 21-year-old female in the inframammary region. We report two cases of fibroadenoma and carcinoma arising from EBT in the axilla of a 26 and 45-year females. Fibroadenoma was treated by simple excision while for carcinoma modified radical mastectomy was done followed by radiation and chemotherapy. Patient developed metastasis in the sternum. Carcinoma arising from EBT has a poorer prognosis and needs early diagnosis and treatment.

  1. HER1-4 protein concentrations in normal breast tissue from breast cancer patients are expressed by the same profile as in the malignant tissue

    DEFF Research Database (Denmark)

    Olsen, Dorte Aa; Ostergaard, Birthe; Bokmand, Susanne;

    2009-01-01

    and the proteins extracted. The tissue and serum concentrations of HER1-4 were determined quantitatively using a commercially available enzyme linked immunosorbent assay (ELISA) method. Results: HER1 was down regulated in cancer tissue when compared to autologous reference tissue (p=8x10(-6)), while HER2 (p...-4 system. We have mapped the protein concentrations of HER1-4 in breast cancer tissue, autologous reference tissue, normal breast tissue and serum samples, to see whether non-cancer cells from these patients express a protein profile indicating general activation. Methods: Tissue samples from malignant...

  2. Differential Epigenetic Effects of Atmospheric Cold Plasma on MCF-7 and MDA-MB-231 Breast Cancer Cells.

    Science.gov (United States)

    Park, Sung-Bin; Kim, Byungtak; Bae, Hansol; Lee, Hyunkyung; Lee, Seungyeon; Choi, Eun H; Kim, Sun Jung

    2015-01-01

    Cold atmospheric plasma (plasma) has emerged as a novel tool for a cancer treatment option, having been successfully applied to a few types of cancer cells, as well as tissues. However, to date, no studies have been performed to examine the effect of plasma on epigenetic alterations, including CpG methylation. In this study, the effects of plasma on DNA methylation changes in breast cancer cells were examined by treating cultured MCF-7 and MDA-MB-231 cells, representing estrogen-positive and estrogen-negative cancer cells, respectively, with plasma. A pyrosequencing analysis of Alu indicated that a specific CpG site was induced to be hypomethylated from 23.4 to 20.3% (p plasma treatment in the estrogen-negative MDA-MB-231 cells only. A genome-wide methylation analysis identified "cellular movement, connective tissue development and function, tissue development" and "cell-to-cell signaling and interaction, cell death and survival, cellular development" as the top networks. Of the two cell types, the MDA-MB-231 cells underwent a higher rate of apoptosis and a decreased proliferation rate upon plasma treatment. Taken together, these results indicate that plasma induces epigenetic and cellular changes in a cell type-specific manner, suggesting that a careful screening of target cells and tissues is necessary for the potential application of plasma as a cancer treatment option.

  3. Differential Epigenetic Effects of Atmospheric Cold Plasma on MCF-7 and MDA-MB-231 Breast Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Sung-Bin Park

    Full Text Available Cold atmospheric plasma (plasma has emerged as a novel tool for a cancer treatment option, having been successfully applied to a few types of cancer cells, as well as tissues. However, to date, no studies have been performed to examine the effect of plasma on epigenetic alterations, including CpG methylation. In this study, the effects of plasma on DNA methylation changes in breast cancer cells were examined by treating cultured MCF-7 and MDA-MB-231 cells, representing estrogen-positive and estrogen-negative cancer cells, respectively, with plasma. A pyrosequencing analysis of Alu indicated that a specific CpG site was induced to be hypomethylated from 23.4 to 20.3% (p < 0.05 by plasma treatment in the estrogen-negative MDA-MB-231 cells only. A genome-wide methylation analysis identified "cellular movement, connective tissue development and function, tissue development" and "cell-to-cell signaling and interaction, cell death and survival, cellular development" as the top networks. Of the two cell types, the MDA-MB-231 cells underwent a higher rate of apoptosis and a decreased proliferation rate upon plasma treatment. Taken together, these results indicate that plasma induces epigenetic and cellular changes in a cell type-specific manner, suggesting that a careful screening of target cells and tissues is necessary for the potential application of plasma as a cancer treatment option.

  4. Detection of lobular structures in normal breast tissue.

    Science.gov (United States)

    Apou, Grégory; Schaadt, Nadine S; Naegel, Benoît; Forestier, Germain; Schönmeyer, Ralf; Feuerhake, Friedrich; Wemmert, Cédric; Grote, Anne

    2016-07-01

    Ongoing research into inflammatory conditions raises an increasing need to evaluate immune cells in histological sections in biologically relevant regions of interest (ROIs). Herein, we compare different approaches to automatically detect lobular structures in human normal breast tissue in digitized whole slide images (WSIs). This automation is required to perform objective and consistent quantitative studies on large data sets. In normal breast tissue from nine healthy patients immunohistochemically stained for different markers, we evaluated and compared three different image analysis methods to automatically detect lobular structures in WSIs: (1) a bottom-up approach using the cell-based data for subsequent tissue level classification, (2) a top-down method starting with texture classification at tissue level analysis of cell densities in specific ROIs, and (3) a direct texture classification using deep learning technology. All three methods result in comparable overall quality allowing automated detection of lobular structures with minor advantage in sensitivity (approach 3), specificity (approach 2), or processing time (approach 1). Combining the outputs of the approaches further improved the precision. Different approaches of automated ROI detection are feasible and should be selected according to the individual needs of biomarker research. Additionally, detected ROIs could be used as a basis for quantification of immune infiltration in lobular structures. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Automatic tissue segmentation of breast biopsies imaged by QPI

    Science.gov (United States)

    Majeed, Hassaan; Nguyen, Tan; Kandel, Mikhail; Marcias, Virgilia; Do, Minh; Tangella, Krishnarao; Balla, Andre; Popescu, Gabriel

    2016-03-01

    The current tissue evaluation method for breast cancer would greatly benefit from higher throughput and less inter-observer variation. Since quantitative phase imaging (QPI) measures physical parameters of tissue, it can be used to find quantitative markers, eliminating observer subjectivity. Furthermore, since the pixel values in QPI remain the same regardless of the instrument used, classifiers can be built to segment various tissue components without need for color calibration. In this work we use a texton-based approach to segment QPI images of breast tissue into various tissue components (epithelium, stroma or lumen). A tissue microarray comprising of 900 unstained cores from 400 different patients was imaged using Spatial Light Interference Microscopy. The training data were generated by manually segmenting the images for 36 cores and labelling each pixel (epithelium, stroma or lumen.). For each pixel in the data, a response vector was generated by the Leung-Malik (LM) filter bank and these responses were clustered using the k-means algorithm to find the centers (called textons). A random forest classifier was then trained to find the relationship between a pixel's label and the histogram of these textons in that pixel's neighborhood. The segmentation was carried out on the validation set by calculating the texton histogram in a pixel's neighborhood and generating a label based on the model learnt during training. Segmentation of the tissue into various components is an important step toward efficiently computing parameters that are markers of disease. Automated segmentation, followed by diagnosis, can improve the accuracy and speed of analysis leading to better health outcomes.

  6. Imaging of human breast tissue using polarization sensitive optical coherence tomography

    Science.gov (United States)

    Verma, Y.; Gautam, M.; Divakar Rao, K.; Swami, M. K.; Gupta, P. K.

    2011-12-01

    We report a study on the use of polarization sensitive optical coherence tomography (PSOCT) for discriminating malignant (invasive ductal carcinoma), benign (fibroadenoma) and normal (adipocytes) breast tissue sites. The results show that while conventional OCT, that utilizes only the intensity of light back-scattered from tissue microstructures, is able to discriminate breast tissues as normal (adipocytes) and abnormal (malignant and benign) tissues, PS-OCT helps in discriminating between malignant and benign tissue sites also. The estimated values of birefringence obtained from the PSOCT imaging show that benign breast tissue samples have significantly higher birefringence as compared to the malignant tissue samples.

  7. Expression of Uncoupling Protein 2 in Breast Cancer Tissue and Drug-resistant Cells

    Institute of Scientific and Technical Information of China (English)

    Sun Yan; Yuan Yuan; Zhang Lili; Zhu Hong; Hu Sainan

    2013-01-01

    Objective:To explore the expression of uncoupling protein-2 (UCP2) in clinical breast cancer tissue and drug-resistant cells. Methods:The expression of UCP2 in breast cancer tissue and normal tissue adjacent to carcinoma as well as breast cancer cell MCF-7 and paclitaxel-resistant cell MX-1/T were respectively detected by immunohistochemistry and Western blot. Results:The expression of UCP2 in breast cancer tissue was signiifcantly higher than in normal tissue adjacent to carcinoma, and that in paclitaxel-resistant cell MX-1/T obviously higher than in breast cancer cell MCF-7. Conclusion:UCP2 is highly expressed in breast cancer tissue and drug-resistant cells.

  8. Relations between antioxidant vitamins in adipose tissue, plasma, and diet

    NARCIS (Netherlands)

    Kardinaal, A.F.M.; Veer, P. van 't; Brants, H.A.M.; Berg, H. van den; Schoonhoven, J. van; Hermus, R.J.J.

    1995-01-01

    For an evaluation of fat-soluble vitamin concentrations in adipose tissue as biomarkers of intake, estimates of usual intake of β-carotene, total vitamin A, and vitamin E (assessed by food frequency questionnaire) were compared with plasma and adipose tissue concentrations of β-carotene, retinol, an

  9. Relations between antioxidant vitamins in adipose tissue, plasma, and diet

    NARCIS (Netherlands)

    Kardinaal, A.F.M.; Veer, P. van 't; Brants, H.A.M.; Berg, H. van den; Schoonhoven, J. van; Hermus, R.J.J.

    1995-01-01

    For an evaluation of fat-soluble vitamin concentrations in adipose tissue as biomarkers of intake, estimates of usual intake of β-carotene, total vitamin A, and vitamin E (assessed by food frequency questionnaire) were compared with plasma and adipose tissue concentrations of β-carotene, retinol, an

  10. How to assess the plasma delivery of RONS into tissue fluid and tissue

    Science.gov (United States)

    Oh, Jun-Seok; Szili, Endre J.; Gaur, Nishtha; Hong, Sung-Ha; Furuta, Hiroshi; Kurita, Hirofumi; Mizuno, Akira; Hatta, Akimitsu; Short, Robert D.

    2016-08-01

    The efficacy of helium (He) and argon (Ar) plasma jets are being investigated for different healthcare applications including wound and cancer therapy, sterilisation and surface disinfections. Current research points to a potential link between the generation of reactive oxygen and nitrogen species (RONS) and outcomes in a range of biological and medical applications. As new data accrue, further strengthening this link, it becomes important to understand the controlled delivery of RONS into solutions, tissue fluids and tissues. This paper investigates the use of He and Ar plasma jets to deliver three RONS (hydrogen peroxide—H2O2, nitrite—\\text{NO}2- and nitrate—\\text{NO}3- ) and molecular oxygen (O2) directly into deionised (DI) water, or indirectly into DI water through an agarose target. The DI water is used in place of tissue fluid and the agarose target serves as a surrogate of tissue. Direct plasma jet treatments deliver more RONS and O2 than the through-agarose treatments for equivalent treatments times. The former only deliver RONS whilst the plasma jets are ignited; the latter continues to deliver RONS into the DI water long after the plasmas are extinguished. The He plasma jet is more effective at delivering H2O2 and \\text{NO}2- directly into DI water, but the Ar plasma jet is more effective at nitrating the DI water in both direct and through-agarose treatments. DI water directly treated with the plasma jets is deoxygenated, with the He plasma jet purging more O2 than the Ar plasma jet. This effect is known as ‘sparging’. In contrast, for through-agarose treatments both jets oxygenated the DI water. These results indicate that in the context of direct and indirect plasma jet treatments of real tissue fluids and tissue, the choice of process gas (He or Ar) could have a profound effect on the concentrations of RONS and O2. Irrespective of operating gas, sparging of tissue fluid (in an open wound) for long prolonged periods during direct plasma

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

    OpenAIRE

    2015-01-01

    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 a...

  12. Proteomic analysis of tissue samples in translational breast cancer research

    DEFF Research Database (Denmark)

    Gromov, Pavel; Moreira, José; Gromova, Irina

    2014-01-01

    , and both prognosis and prediction of outcome of chemotherapy. The purpose of this review is to critically appraise what has been achieved to date using proteomic technologies and to bring forward novel strategies - based on the analysis of clinically relevant samples - that promise to accelerate......In the last decade, many proteomic technologies have been applied, with varying success, to the study of tissue samples of breast carcinoma for protein expression profiling in order to discover protein biomarkers/signatures suitable for: characterization and subtyping of tumors; early diagnosis...

  13. Plasma MMP1 and MMP8 expression in breast cancer: Protective role of MMP8 against lymph node metastasis

    Directory of Open Access Journals (Sweden)

    Christiaens Marie-Rose

    2008-03-01

    Full Text Available Abstract Background Elevated levels of matrix metalloproteinases have been found to associate with poor prognosis in various carcinomas. This study aimed at evaluating plasma levels of MMP1, MMP8 and MMP13 as diagnostic and prognostic markers of breast cancer. Methods A total of 208 breast cancer patients, of which 21 with inflammatory breast cancer, and 42 healthy controls were included. Plasma MMP1, MMP8 and MMP13 levels were measured using ELISA and correlated with clinicopathological characteristics. Results Median plasma MMP1 levels were higher in controls than in breast cancer patients (3.45 vs. 2.01 ng/ml, while no difference was found for MMP8 (10.74 vs. 10.49 ng/ml. ROC analysis for MMP1 revealed an AUC of 0.67, sensitivity of 80% and specificity of 24% at a cut-off value of 4.24 ng/ml. Plasma MMP13 expression could not be detected. No correlation was found between MMP1 and MMP8 levels. We found a trend of lower MMP1 levels with increasing tumour size (p = 0.07; and higher MMP8 levels with premenopausal status (p = 0.06 and NPI (p = 0.04. The median plasma MMP1 (p = 0.02 and MMP8 (p = 0.007 levels in the non-inflammatory breast cancer patients were almost twice as high as those found in the inflammatory breast cancer patients. Intriguingly, plasma MMP8 levels were positively associated with lymph node involvement but showed a negative correlation with the risk of distant metastasis. Both controls and lymph node negative patients (pN0 had lower MMP8 levels than patients with moderate lymph node involvement (pN1, pN2 (p = 0.001; and showed a trend for higher MMP8 levels compared to patients with extensive lymph node involvement (pN3 and a strong predisposition to distant metastasis (p = 0.11. Based on the hypothesis that blood and tissue protein levels are in reverse association, these results suggest that MMP8 in the tumour may have a protective effect against lymph node metastasis. Conclusion In summary, we observed differences in MMP1

  14. Air plasma treatment of liquid covered tissue: long timescale chemistry

    Science.gov (United States)

    Lietz, Amanda M.; Kushner, Mark J.

    2016-10-01

    Atmospheric pressure plasmas have shown great promise for the treatment of wounds and cancerous tumors. In these applications, the sample is usually covered by a thin layer of a biological liquid. The reactive oxygen and nitrogen species (RONS) generated by the plasma activate and are processed by the liquid before the plasma produced activation reaches the tissue. The synergy between the plasma and the liquid, including evaporation and the solvation of ions and neutrals, is critical to understanding the outcome of plasma treatment. The atmospheric pressure plasma sources used in these procedures are typically repetitively pulsed. The processes activated by the plasma sources have multiple timescales—from a few ns during the discharge pulse to many minutes for reactions in the liquid. In this paper we discuss results from a computational investigation of plasma-liquid interactions and liquid phase chemistry using a global model with the goal of addressing this large dynamic range in timescales. In modeling air plasmas produced by a dielectric barrier discharge over liquid covered tissue, 5000 voltage pulses were simulated, followed by 5 min of afterglow. Due to the accumulation of long-lived species such as ozone and N x O y , the gas phase dynamics of the 5000th discharge pulse are different from those of the first pulse, particularly with regards to the negative ions. The consequences of applied voltage, gas flow, pulse repetition frequency, and the presence of organic molecules in the liquid on the gas and liquid reactive species are discussed.

  15. Tumor tissue protein signatures reflect histological grade of breast cancer.

    Science.gov (United States)

    Skoog, Petter; Ohlsson, Mattias; Fernö, Mårten; Rydén, Lisa; Borrebaeck, Carl A K; Wingren, Christer

    2017-01-01

    Histological grade is one of the most commonly used prognostic factors for patients diagnosed with breast cancer. However, conventional grading has proven technically challenging, and up to 60% of the tumors are classified as histological grade 2, which represents a heterogeneous cohort less informative for clinical decision making. In an attempt to study and extend the molecular puzzle of histologically graded breast cancer, we have in this pilot project searched for additional protein biomarkers in a new space of the proteome. To this end, we have for the first time performed protein expression profiling of breast cancer tumor tissue, using recombinant antibody microarrays, targeting mainly immunoregulatory proteins. Thus, we have explored the immune system as a disease-specific sensor (clinical immunoproteomics). Uniquely, the results showed that several biologically relevant proteins reflecting histological grade could be delineated. In more detail, the tentative biomarker panels could be used to i) build a candidate model classifying grade 1 vs. grade 3 tumors, ii) demonstrate the molecular heterogeneity among grade 2 tumors, and iii) potentially re-classify several of the grade 2 tumors to more like grade 1 or grade 3 tumors. This could, in the long-term run, lead to improved prognosis, by which the patients could benefit from improved tailored care.

  16. Tissue architecture: the ultimate regulator of breast epithelial function

    Energy Technology Data Exchange (ETDEWEB)

    Bissell, Mina J; Rizki, Aylin; Mian, Saira

    2003-10-20

    discuss the following: first, how our laboratory came to develop a model of the mammary gland acinus; second, what this model has told us about mechanisms that govern tissue specificity and malignancy; and third, possible directions for future studies. We summarize the evidence for the central role of ECM signaling in the maintenance of mammary function in culture and (more briefly) its role in tumorigenesis. This is followed by a discussion of the role that tissue architecture and tissue polarity (as opposed to cell polarity) may play in these processes. In an elegantly written and reasoned essay, Kirschner et al. coined the new science of developmental biology 'molecular vitalism'. They framed new concepts for self-organization as well as schemes for information flow in biological organization. Rao et al. reviewed and elaborated on differential-equation-based models of biochemical reaction networks and intracellular noise, with emphasis on bacteria and phage. Similarly, Hartwell et al. discussed the synergy between experiment and theory in elucidating 'modules' - collections of interacting molecules - and in unraveling how these modules collaborate to perform cellular functions such as signal transduction. We believe that many of these ideas will also be applicable to the maintenance of tissue specificity. As much as we agree with Kirschner et al. regarding the limitations of the machine analogy to biological systems, we conclude with thoughts on how we may proceed to model the complex tissue networks that govern breast tissue architecture. We suggest that our understanding of the structure and function of breast tissue would benefit from examining recent techniques for modeling large complex networks such as the World Wide Web and the Internet backbone among others.

  17. Elevated pre-treatment levels of plasma C-reactive protein are associated with poor prognosis after breast cancer

    DEFF Research Database (Denmark)

    Allin, Kristine H; Nordestgaard, Børge G; Flyger, Henrik;

    2011-01-01

    We examined whether plasma C-reactive protein (CRP) levels at the time of diagnosis of breast cancer are associated with overall survival, disease-free survival, death from breast cancer, and recurrence of breast cancer.......We examined whether plasma C-reactive protein (CRP) levels at the time of diagnosis of breast cancer are associated with overall survival, disease-free survival, death from breast cancer, and recurrence of breast cancer....

  18. Differential promoter methylation of kinesin family member 1a in plasma is associated with breast cancer and DNA repair capacity

    Science.gov (United States)

    GUERRERO-PRESTON, RAFAEL; HADAR, TAL; OSTROW, KIMBERLY LASKIE; SOUDRY, ETHAN; ECHENIQUE, MIGUEL; ILI-GANGAS, CARMEN; PÉREZ, GABRIELA; PEREZ, JIMENA; BREBI-MIEVILLE, PRISCILLA; DESCHAMPS, JOSÉ; MORALES, LUISA; BAYONA, MANUEL; SIDRANSKY, DAVID; MATTA, JAIME

    2014-01-01

    Methylation alterations of CpG islands, CpG island shores and first exons are key events in the formation and progression of human cancer, and an increasing number of differentially methylated regions and genes have been identified in breast cancer. Recent studies of the breast cancer methylome using deep sequencing and microarray platforms are providing a novel insight on the different roles aberrant methylation plays in molecular subtypes of breast cancer. Accumulating evidence from a subset of studies suggests that promoter methylation of tumor-suppressor genes associated with breast cancer can be quantified in circulating DNA. However, there is a paucity of studies that examine the combined presence of genetic and epigenetic alterations associated with breast cancer using blood-based assays. Dysregulation of DNA repair capacity (DRC) is a genetic risk factor for breast cancer that has been measured in lymphocytes. We isolated plasma DNA from 340 participants in a breast cancer case control project to study promoter methylation levels of five genes previously shown to be associated with breast cancer in frozen tissue and in cell line DNA: MAL, KIF1A, FKBP4, VGF and OGDHL. Methylation of at least one gene was found in 49% of the cases compared to 20% of the controls. Three of the four genes had receiver characteristic operator curve values of ≥0.50: MAL (0.64), KIF1A (0.51) and OGDHL (0.53). KIF1A promoter methylation was associated with breast cancer and inversely associated with DRC. This is the first evidence of a significant association between genetic and epigenetic alterations in breast cancer using blood-based tests. The potential diagnostic utility of these biomarkers and their relevance for breast cancer risk prediction should be examined in larger cohorts. PMID:24927296

  19. Cell-graph mining for breast tissue modeling and classification.

    Science.gov (United States)

    Bilgin, Cagatay; Demir, Cigdem; Nagi, Chandandeep; Yener, Bulent

    2007-01-01

    We consider the problem of automated cancer diagnosis in the context of breast tissues. We present graph theoretical techniques that identify and compute quantitative metrics for tissue characterization and classification. We segment digital images of histopatological tissue samples using k-means algorithm. For each segmented image we generate different cell-graphs using positional coordinates of cells and surrounding matrix components. These cell-graphs have 500-2000 cells(nodes) with 1000-10000 links depending on the tissue and the type of cell-graph being used. We calculate a set of global metrics from cell-graphs and use them as the feature set for learning. We compare our technique, hierarchical cell graphs, with other techniques based on intensity values of images, Delaunay triangulation of the cells, the previous technique we proposed for brain tissue images and with the hybrid approach that we introduce in this paper. Among the compared techniques, hierarchical-graph approach gives 81.8% accuracy whereas we obtain 61.0%, 54.1% and 75.9% accuracy with intensity-based features, Delaunay triangulation and our previous technique, respectively.

  20. Breast tissue characterization using FARMA modeling of ultrasonic RF echo.

    Science.gov (United States)

    Alacam, Burak; Yazici, Birsen; Bilgutay, Nihat; Forsberg, Flemming; Piccoli, Catherine

    2004-10-01

    A number of empirical and analytical studies demonstrated that the ultrasound RF echo reflected from tissue exhibits 1/f characteristics. In this paper, we propose to model 1/f characteristics of the ultrasonic RF echo by a novel parsimonious model, namely the fractional differencing auto regressive moving average (FARMA) process, and evaluated diagnostic value of model parameters for breast cancer malignancy differentiation. FARMA model captures the fractal and long term correlated nature of the backscattered speckle texture and facilitates robust efficient estimation of fractal parameters. In our study, in addition to the computer generated FARMA model parameters, we included patient age and radiologist's prebiopsy level of suspicion (LOS) as potential indicators of malignant and benign masses. We evaluated the performance of the proposed set of features using various classifiers and training methods using 120 in vivo breast images. Our study shows that the area under the receiver operating characteristics (ROC) curve of FARMA model parameters alone is superior to the area under the ROC curve of the radiologist's prebiopsy LOS. The area under the ROC curve of the three sets of features yields a value of 0.87, with a confidence interval of [0.85, 0.89], at a significance level of 0.05. Our results suggest that the proposed method of ultrasound RF echo model leads to parameters that can differentiate breast tumors with a relatively high precision. This set of RF echo features can be incorporated into a comprehensive computer-aided diagnostic system to aid physicians in breast cancer diagnosis.

  1. Breast tissue segmentation from x-ray radiographs

    Science.gov (United States)

    Chen, Chen; Nielsen, Mads; Karssemeijer, Nico; Brandt, Sami S.

    2014-05-01

    In this paper, we propose a robust and accurate method that segments mammograms to three distinct regions: breast tissue, pectoral muscle and background. Our approach is built around a neural, two-layer committee machine. On the first layer, individual experts, each formed by a feature vector and a classifier, vote the local class label of the mammogram. The votes are given as an input, together with a prior map, to the second layer of the committee machine, which combines the inputs by a gating network. As the first layer features, we use effective, well-known local features based on image intensity, intensity histograms, local binary patterns, and histograms of oriented gradient. As with the first-layer classifiers and the gating network, we use support vector machines. Our experiments on a database of 495 mammograms, divided into independent training, validations and test subsets, show that our method is able to segment the breast tissue without failure, and it challenges the manual expert segmentation in the level of accuracy.

  2. Use of proton beams with breast prostheses and tissue expanders

    Energy Technology Data Exchange (ETDEWEB)

    Moyers, Michael F., E-mail: MFMoyers@roadrunner.com [ProCure Proton Therapy Center, Somerset, NJ (United States); Mah, Dennis; Boyer, Sean P.; Chang, Chang [ProCure Proton Therapy Center, Somerset, NJ (United States); Pankuch, Mark [ProCure Proton Therapy Center, Warrenville, IL (United States)

    2014-04-01

    Since the early 2000s, a small but rapidly increasing number of patients with breast cancer have been treated with proton beams. Some of these patients have had breast prostheses or tissue expanders in place during their courses of treatment. Procedures must be implemented to plan the treatments of these patients. The density, kilovoltage x-ray computed tomography numbers (kVXCTNs), and proton relative linear stopping powers (pRLSPs) were calculated and measured for several test sample devices. The calculated and measured kVXCTNs of saline were 1% and 2.4% higher than the values for distilled water while the calculated RLSP for saline was within 0.2% of the value for distilled water. The measured kVXCTN and pRLSP of the silicone filling material for the test samples were approximately 1120 and 0.935, respectively. The conversion of kVXCTNs to pRLSPs by the treatment planning system standard tissue conversion function is adequate for saline-filled devices but for silicone-filled devices manual reassignment of the pRLSPs is required.

  3. Use of proton beams with breast prostheses and tissue expanders.

    Science.gov (United States)

    Moyers, Michael F; Mah, Dennis; Boyer, Sean P; Chang, Chang; Pankuch, Mark

    2014-01-01

    Since the early 2000s, a small but rapidly increasing number of patients with breast cancer have been treated with proton beams. Some of these patients have had breast prostheses or tissue expanders in place during their courses of treatment. Procedures must be implemented to plan the treatments of these patients. The density, kilovoltage x-ray computed tomography numbers (kVXCTNs), and proton relative linear stopping powers (pRLSPs) were calculated and measured for several test sample devices. The calculated and measured kVXCTNs of saline were 1% and 2.4% higher than the values for distilled water while the calculated RLSP for saline was within 0.2% of the value for distilled water. The measured kVXCTN and pRLSP of the silicone filling material for the test samples were approximately 1120 and 0.935, respectively. The conversion of kVXCTNs to pRLSPs by the treatment planning system standard tissue conversion function is adequate for saline-filled devices but for silicone-filled devices manual reassignment of the pRLSPs is required. © 2013 Published by American Association of Medical Dosimetrists on behalf of American Association of Medical Dosimetrists.

  4. Fibroadenomatosis involving bilateral breasts and axillary accessory breast tissues in a renal transplant recipient given cyclosporin A.

    Science.gov (United States)

    Bulakci, Mesut; Gocmez, Ahmet; Demir, Ali Aslan; Salmaslioglu, Artur; Tukenmez, Mustafa; Yavuz, Ekrem; Acunas, Gulden

    2014-10-01

    We present the mammographic and sonographic findings in a case of fibroadenomatosis involving both breasts and axillae in a renal transplant patient after 16 years of treatment with cyclosporin A. Awareness of the fact that cyclosporin A may induce the formation of fibroadenomas, including in accessory breast tissue, is important for correct diagnosis and preventing unnecessary intervention. © 2014 Wiley Periodicals, Inc.

  5. Progesterone and adiponectin receptor family member 3 expression and clinical significance in breast cancer tissues

    Institute of Scientific and Technical Information of China (English)

    Xiao-Qiang Dai; Hai-Liang Zhang; Hong-Mei Li

    2016-01-01

    Objective:To discuss progesterone and adiponectin receptor family member 3 expression and clinical significance in breast cancer tissues. Method:A total of 90 cases with breast cancer who were admitted in our hospital from Jan 2000 to Jan 2010 were selected. Meanwhile, normal tumor-adjacent breast tissues were selected as comparison. Diagnosis of all patients was confirmed by postoperative pathological examinations. Immunohistochemistry method was adopted to detect PAQR3 protein expression in breast cancer tissues and normal tumor-adjacent breast tissues and its clinical significance was discussed. Results:PAQR3 protein positive expression rate in breast cancer tissues was 25.6%, which was significantly lower than that (78.9%) in normal tumor-adjacent breast tissues;PAQR3 protein positive expression rate had nothing to do with age, tumor size, pathological types and differentiated degree of patients, but had significant correlation with TNM staging and lymphatic metastasis existence of patients. Kaplan–Meier survival analysis results showed that five years survival rate of patients with PAQR3 protein positive expression was significantly higher than whom with negative expression. Conclusion:PAQR3 protein expression in breast cancer tissues was significantly reduced, which indicated that PAQR3 protein possibly played an important role in pathogenesis of breast cancer.

  6. Secretome analysis of breast cancer-associated adipose tissue to identify paracrine regulators of breast cancer growth

    Science.gov (United States)

    Lore, Lapeire; An, Hendrix; Evelyne, Lecoutere; Mieke, Van Bockstal; Jo, Vandesompele; Dawn, Maynard; Geert, Braems; Rudy, Van Den Broecke; Cathérine, Müller; Marc, Bracke; Véronique, Cocquyt; Hannelore, Denys; Olivier, De Wever

    2017-01-01

    Adipose tissue secretes a plethora of adipokines as evidenced by characterization of subcutaneous and visceral adipose tissue secretomes. However, adipose tissue composition and secretion pattern is depot and disease dependent, influencing the adipose tissue secretome. We investigated the secretome of cancer-associated adipose tissue (CAAT) explants from breast cancer patients and explored its role in breast cancer proliferation. CAAT proteins were identified by LC-MS/MS and human protein antibody arrays and stimulated proliferation of three breast cancer cell lines. Kinomics and transcriptomics of MCF-7 breast cancer cells treated with the secretome of CAAT revealed activation of Akt-, ERK- and JNK-pathways and differential expression of activator protein 1 (AP-1) and cAMP responsive element-binding protein (CREB) target genes. The cyclin-dependent kinase (CDK)4/6-inhibitor palbociclib significantly abrogated CAAT-enhanced breast cancer cell proliferation. Our work characterizes the specific breast CAAT protein secretome and reveals its pro-proliferative potency in breast cancer. PMID:28525384

  7. Analysis of elemental concentration censored distributions in breast malignant and breast benign neoplasm tissues

    Energy Technology Data Exchange (ETDEWEB)

    Kubala-Kukus, A. [Institute of Physics, Swietokrzyska Academy, Swietokrzyska 15, 25-406 Kielce (Poland); Holycross Cancer Centre, Artwinskiego 3, 25-734 Kielce (Poland)], E-mail: Aldona.Kubala-Kukus@pu.kielce.pl; Banas, D.; Braziewicz, J. [Institute of Physics, Swietokrzyska Academy, Swietokrzyska 15, 25-406 Kielce (Poland); Holycross Cancer Centre, Artwinskiego 3, 25-734 Kielce (Poland); Gozdz, S. [Holycross Cancer Centre, Artwinskiego 3, 25-734 Kielce (Poland); Majewska, U. [Institute of Physics, Swietokrzyska Academy, Swietokrzyska 15, 25-406 Kielce (Poland); Holycross Cancer Centre, Artwinskiego 3, 25-734 Kielce (Poland); Pajek, M. [Institute of Physics, Swietokrzyska Academy, Swietokrzyska 15, 25-406 Kielce (Poland)

    2007-07-15

    The total reflection X-ray fluorescence method was applied to study the trace element concentrations in human breast malignant and breast benign neoplasm tissues taken from the women who were patients of Holycross Cancer Centre in Kielce (Poland). These investigations were mainly focused on the development of new possibilities of cancer diagnosis and therapy monitoring. This systematic comparative study was based on relatively large ({approx} 100) population studied, namely 26 samples of breast malignant and 68 samples of breast benign neoplasm tissues. The concentrations, being in the range from a few ppb to 0.1%, were determined for thirteen elements (from P to Pb). The results were carefully analysed to investigate the concentration distribution of trace elements in the studied samples. The measurements of concentration of trace elements by total reflection X-ray fluorescence were limited, however, by the detection limit of the method. It was observed that for more than 50% of elements determined, the concentrations were not measured in all samples. These incomplete measurements were treated within the statistical concept called left-random censoring and for the estimation of the mean value and median of censored concentration distributions, the Kaplan-Meier estimator was used. For comparison of concentrations in two populations, the log-rank test was applied, which allows to compare the censored total reflection X-ray fluorescence data. Found statistically significant differences are discussed in more details. It is noted that described data analysis procedures should be the standard tool to analyze the censored concentrations of trace elements analysed by X-ray fluorescence methods.

  8. Analysis of elemental concentration censored distributions in breast malignant and breast benign neoplasm tissues

    Science.gov (United States)

    Kubala-Kukuś, A.; Banaś, D.; Braziewicz, J.; Góźdź, S.; Majewska, U.; Pajek, M.

    2007-07-01

    The total reflection X-ray fluorescence method was applied to study the trace element concentrations in human breast malignant and breast benign neoplasm tissues taken from the women who were patients of Holycross Cancer Centre in Kielce (Poland). These investigations were mainly focused on the development of new possibilities of cancer diagnosis and therapy monitoring. This systematic comparative study was based on relatively large (˜ 100) population studied, namely 26 samples of breast malignant and 68 samples of breast benign neoplasm tissues. The concentrations, being in the range from a few ppb to 0.1%, were determined for thirteen elements (from P to Pb). The results were carefully analysed to investigate the concentration distribution of trace elements in the studied samples. The measurements of concentration of trace elements by total reflection X-ray fluorescence were limited, however, by the detection limit of the method. It was observed that for more than 50% of elements determined, the concentrations were not measured in all samples. These incomplete measurements were treated within the statistical concept called left-random censoring and for the estimation of the mean value and median of censored concentration distributions, the Kaplan-Meier estimator was used. For comparison of concentrations in two populations, the log-rank test was applied, which allows to compare the censored total reflection X-ray fluorescence data. Found statistically significant differences are discussed in more details. It is noted that described data analysis procedures should be the standard tool to analyze the censored concentrations of trace elements analysed by X-ray fluorescence methods.

  9. Irradiated HMEC from A-T Heterozygous Breast Tissue

    Science.gov (United States)

    Richmond, Robert; Bors, Karen; Cruz, Angela; Pettengil, Olive; Curreri, Peter A. (Technical Monitor)

    2002-01-01

    Women who are heterozygous for ataxia-telangiectasia (A-T) carry a single defective ATM gene in chromosome 11 q22-23, and have been statistically determined with high significance within a defined database to be approximately 5-fold more susceptible for developing breast cancer than their noma1 counterpart. Breast cancer susceptibility of these A-T heterozygotes has been hypothesized to include consequence of response to damage caused by low levels of ionizing radiation. Prophylactic mastectomy specimens were donated by a 41 year-old obligate A-T heterozygote who was located prior to her elective surgery through an existing pedigree. Harvest of that breast tissue provided an isolate of long-term growth human mammary epithelial cells (HMEC), designated WH612/3. An isolate of presumed normal long-term growth HMEC, designated 48R, was obtained from Dr. Martha Stampfer (Lawrence Berkeley Laboratory, University of California), and the A-T heterozygous HMEC were transformed with E6 and E7 oncogenes of human papilloma virus Type-16 in the laboratory of Dr. Ray White (Hunt- Cancer Institute, University of Utah) for use in this study. The objective of this study is to study the expression of end points that may bear on cancer outcome following irradiation of HMEC. Specific end points are cell survival, cell cycle, p53 expression, and apoptosis. Survival curves, immunostaining, and flow cytometery are used to examine these end points. Radiation-induced cell killing shows less shoulder development in the survival curve for WH61U3 compared to 48R HMEC, suggesting less repair of damage in the former HMEC. Additional information is included in the original extended abstract.

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

    Directory of Open Access Journals (Sweden)

    Zach S. Templeton

    2015-12-01

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

  11. Brown adipose tissue takes up plasma triglycerides mostly after lipolysis

    NARCIS (Netherlands)

    Khedoe, P.P.S.J.; Hoeke, Geerte; Kooijman, Sander; Dijk, Wieneke; Buijs, Jeroen T.; Kersten, Sander; Havekes, Louis M.; Hiemstra, Pieter S.; Berbée, Jimmy F.P.; Boon, Mariëtte R.; Rensen, Patrick C.N.

    2015-01-01

    Brown adipose tissue (BAT) produces heat by burning TGs that are stored within intracellular lipid droplets and need to be replenished by the uptake of TG-derived FA from plasma. It is currently unclear whether BAT takes up FA via uptake of TG-rich lipoproteins (TRLs), after lipolysis-mediated li

  12. Comparison of Patient-reported Outcomes after Implant Versus Autologous Tissue Breast Reconstruction Using the BREAST-Q

    Science.gov (United States)

    Pirro, Ortensia; Vindigni, Vincenzo; Sukop, Andrej; Hromadkova, Veronika; Nguyenova, Alena; Vitova, Lenka; Bassetto, Franco

    2017-01-01

    Background: The demand for reconstructive breast procedures of various types has accelerated in recent years. Coupled with increased patient expectations, it has fostered the development of oncoplastic and reconstructive techniques in breast surgery. In the setting of postmastectomy reconstruction, patient satisfaction and quality of life are the most significant outcome variables when evaluating surgical success. The aim of this study was to evaluate the quality of life after implant breast reconstruction compared with autologous breast reconstruction. Materials and Methods: A cross-sectional study design was used. A total of 65 women who had completed postmastectomy implant-based or autologous reconstruction in the participating center were asked to complete the BREAST-Q (Reconstruction Module). Results: Data analysis demonstrated that women with autologous breast reconstruction were significantly more satisfied with their breasts (P = 0.0003) and with the overall outcome (P = 0.0001) compared with women with implant breast reconstruction. All other BREAST-Q parameters that were considered and observed were not significantly different between the 2 patient groups. Conclusions: Through statistical analysis, our results showed that patients who underwent autologous tissue reconstruction had better satisfaction with the reconstructed breast and the outcome, while both techniques appear to equally improve psychosocial well-being, sexual well-being, and chest satisfaction. PMID:28203513

  13. Comparison of Patient-reported Outcomes after Implant Versus Autologous Tissue Breast Reconstruction Using the BREAST-Q.

    Science.gov (United States)

    Pirro, Ortensia; Mestak, Ondrej; Vindigni, Vincenzo; Sukop, Andrej; Hromadkova, Veronika; Nguyenova, Alena; Vitova, Lenka; Bassetto, Franco

    2017-01-01

    The demand for reconstructive breast procedures of various types has accelerated in recent years. Coupled with increased patient expectations, it has fostered the development of oncoplastic and reconstructive techniques in breast surgery. In the setting of postmastectomy reconstruction, patient satisfaction and quality of life are the most significant outcome variables when evaluating surgical success. The aim of this study was to evaluate the quality of life after implant breast reconstruction compared with autologous breast reconstruction. A cross-sectional study design was used. A total of 65 women who had completed postmastectomy implant-based or autologous reconstruction in the participating center were asked to complete the BREAST-Q (Reconstruction Module). Data analysis demonstrated that women with autologous breast reconstruction were significantly more satisfied with their breasts (P = 0.0003) and with the overall outcome (P = 0.0001) compared with women with implant breast reconstruction. All other BREAST-Q parameters that were considered and observed were not significantly different between the 2 patient groups. Through statistical analysis, our results showed that patients who underwent autologous tissue reconstruction had better satisfaction with the reconstructed breast and the outcome, while both techniques appear to equally improve psychosocial well-being, sexual well-being, and chest satisfaction.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  16. X-Ray Methods to Estimate Breast Density Content in Breast Tissue

    Science.gov (United States)

    Maraghechi, Borna

    This work focuses on analyzing x-ray methods to estimate the fat and fibroglandular contents in breast biopsies and in breasts. The knowledge of fat in the biopsies could aid in their wide-angle x-ray scatter analyses. A higher mammographic density (fibrous content) in breasts is an indicator of higher cancer risk. Simulations for 5 mm thick breast biopsies composed of fibrous, cancer, and fat and for 4.2 cm thick breast fat/fibrous phantoms were done. Data from experimental studies using plastic biopsies were analyzed. The 5 mm diameter 5 mm thick plastic samples consisted of layers of polycarbonate (lexan), polymethyl methacrylate (PMMA-lucite) and polyethylene (polyet). In terms of the total linear attenuation coefficients, lexan ≡ fibrous, lucite ≡ cancer and polyet ≡ fat. The detectors were of two types, photon counting (CdTe) and energy integrating (CCD). For biopsies, three photon counting methods were performed to estimate the fat (polyet) using simulation and experimental data, respectively. The two basis function method that assumed the biopsies were composed of two materials, fat and a 50:50 mixture of fibrous (lexan) and cancer (lucite) appears to be the most promising method. Discrepancies were observed between the results obtained via simulation and experiment. Potential causes are the spectrum and the attenuation coefficient values used for simulations. An energy integrating method was compared to the two basis function method using experimental and simulation data. A slight advantage was observed for photon counting whereas both detectors gave similar results for the 4.2 cm thick breast phantom simulations. The percentage of fibrous within a 9 cm diameter circular phantom of fibrous/fat tissue was estimated via a fan beam geometry simulation. Both methods yielded good results. Computed tomography (CT) images of the circular phantom were obtained using both detector types. The radon transforms were estimated via four energy integrating

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

    Directory of Open Access Journals (Sweden)

    Marcus Nascimento Borges

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

  18. Body mass index associated with genome-wide methylation in breast tissue.

    Science.gov (United States)

    Hair, Brionna Y; Xu, Zongli; Kirk, Erin L; Harlid, Sophia; Sandhu, Rupninder; Robinson, Whitney R; Wu, Michael C; Olshan, Andrew F; Conway, Kathleen; Taylor, Jack A; Troester, Melissa A

    2015-06-01

    Gene expression studies indicate that body mass index (BMI) is associated with molecular pathways involved in inflammation, insulin-like growth factor activation, and other carcinogenic processes in breast tissue. The goal of this study was to determine whether BMI is associated with gene methylation in breast tissue and to identify pathways that are commonly methylated in association with high BMI. Epigenome-wide methylation profiles were determined using the Illumina HumanMethylation450 BeadChip array in the non-diseased breast tissue of 81 women undergoing breast surgery between 2009 and 2013 at the University of North Carolina Hospitals. Multivariable, robust linear regression was performed to identify methylation sites associated with BMI at a false discovery rate q value breast tissue and may influence epigenetic pathways involved in inflammatory and other carcinogenic processes.

  19. The Sodium Iodide Symporter (NIS) and Potential Regulators in Normal, Benign and Malignant Human Breast Tissue

    OpenAIRE

    James Ryan; Curran, Catherine E.; Emer Hennessy; John Newell; Morris, John C.; Kerin, Michael J.; Dwyer, Roisin M

    2011-01-01

    INTRODUCTION: The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro. METHODS: Human breast tissue specimens (malignant n = 75, normal n = 15, fibroadenoma n = 10) were analysed by RQ-PCR targeting NIS, receptors for retinoic acid (RARα, RARβ), oestrogen (ERα), t...

  20. Combinations of parabens at concentrations measured in human breast tissue can increase proliferation of MCF-7 human breast cancer cells.

    Science.gov (United States)

    Charles, Amelia K; Darbre, Philippa D

    2013-05-01

    The alkyl esters of p-hydroxybenzoic acid (parabens), which are used as preservatives in consumer products, possess oestrogenic activity and have been measured in human breast tissue. This has raised concerns for a potential involvement in the development of human breast cancer. In this paper, we have investigated the extent to which proliferation of MCF-7 human breast cancer cells can be increased by exposure to the five parabens either alone or in combination at concentrations as recently measured in 160 human breast tissue samples. Determination of no-observed-effect concentrations (NOEC), lowest-observed-effect concentrations (LOEC), EC50 and EC100 values for stimulation of proliferation of MCF-7 cells by five parabens revealed that 43/160 (27%) of the human breast tissue samples contained at least one paraben at a concentration ≥ LOEC and 64/160 (40%) > NOEC. Proliferation of MCF-7 cells could be increased by combining all five parabens at concentrations down to the 50(th) percentile (median) values measured in the tissues. For the 22 tissue samples taken at the site of ER + PR + primary cancers, 12 contained a sufficient concentration of one or more paraben to stimulate proliferation of MCF-7 cells. This demonstrates that parabens, either alone or in combination, are present in human breast tissue at concentrations sufficient to stimulate the proliferation of MCF-7 cells in vitro, and that functional consequences of the presence of paraben in human breast tissue should be assessed on the basis of all five parabens and not single parabens individually. Copyright © 2013 John Wiley & Sons, Ltd.

  1. Prevalence of Ectopic Breast Tissue and Tumor: A 20-Year Single Center Experience.

    Science.gov (United States)

    Famá, Fausto; Cicciú, Marco; Sindoni, Alessandro; Scarfó, Paola; Pollicino, Andrea; Giacobbe, Giuseppa; Buccheri, Giancarlo; Taranto, Filippo; Palella, Jessica; Gioffré-Florio, Maria

    2016-08-01

    Ectopic breast tissue, which includes both supernumerary breast and aberrant breast tissue, is the most common congenital breast abnormality. Ectopic breast cancers are rare neoplasms that occur in 0.3% to 0.6% of all cases of breast cancer. We retrospectively report, using a large series of breast abnormalities diagnosed and treated, our clinical experience on the management of the ectopic breast cancer. In 2 decades, we observed 327 (2.7%) patients with ectopic breast tissue out of a total of 12,177 subjects undergoing a breast visit for lesions. All patients were classified into 8 classes, according to the classification of Kajava, and assessed by a physician examination, ultrasounds, and, when appropriate, further studies with fine needle aspiration cytology and mammography. All specimens were submitted to the anatomo-pathologist. The most frequent benign histological diagnosis was fibrocystic disease. A rare granulosa cell tumor was also found in the right anterior thoracic wall of 1 patient. Four malignancies were also diagnosed in 4 women: an infiltrating lobular cancer in 1 patient with a lesion classified as class I, and an infiltrating apocrine carcinoma, an infiltrating ductal cancer, and an infiltrating ductal cancer with tubular pattern, occurring in 3 patients with lesions classified as class IV. Only 1 recurrence was observed. We recommend an earlier surgical approach for patients with lesions from class I to IV. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Measurement of paraben concentrations in human breast tissue at serial locations across the breast from axilla to sternum.

    Science.gov (United States)

    Barr, L; Metaxas, G; Harbach, C A J; Savoy, L A; Darbre, P D

    2012-03-01

    The concentrations of five esters of p-hydroxybenzoic acid (parabens) were measured using HPLC-MS/MS at four serial locations across the human breast from axilla to sternum using human breast tissue collected from 40 mastectomies for primary breast cancer in England between 2005 and 2008. One or more paraben esters were quantifiable in 158/160 (99%) of the tissue samples and in 96/160 (60%) all five esters were measured. Variation was notable with respect to individual paraben esters, location within one breast and similar locations in different breasts. Overall median values in nanograms per gram tissue for the 160 tissue samples were highest for n-propylparaben [16.8 (range 0-2052.7)] and methylparaben [16.6 (range 0-5102.9)]; levels were lower for n-butylparaben [5.8 (range 0-95.4)], ethylparaben [3.4 (range 0-499.7)] and isobutylparaben 2.1 (range 0-802.9). The overall median value for total paraben was 85.5 ng g(-1) tissue (range 0-5134.5). The source of the paraben cannot be identified, but paraben was measured in the 7/40 patients who reported never having used underarm cosmetics in their lifetime. No correlations were found between paraben concentrations and age of patient (37-91 years), length of breast feeding (0-23 months), tumour location or tumour oestrogen receptor content. In view of the disproportionate incidence of breast cancer in the upper outer quadrant, paraben concentrations were compared across the four regions of the breast: n-propylparaben was found at significantly higher levels in the axilla than mid (P = 0.004 Wilcoxon matched pairs) or medial (P = 0.021 Wilcoxon matched pairs) regions (P = 0.010 Friedman ANOVA).

  3. Serum estradiol levels associated with specific gene expression patterns in normal breast tissue and in breast carcinomas

    Directory of Open Access Journals (Sweden)

    Kristensen Vessela N

    2011-08-01

    Full Text Available Abstract Background High serum levels of estradiol are associated with increased risk of postmenopausal breast cancer. Little is known about the gene expression in normal breast tissue in relation to levels of circulating serum estradiol. Methods We compared whole genome expression data of breast tissue samples with serum hormone levels using data from 79 healthy women and 64 breast cancer patients. Significance analysis of microarrays (SAM was used to identify differentially expressed genes and multivariate linear regression was used to identify independent associations. Results Six genes (SCGB3A1, RSPO1, TLN2, SLITRK4, DCLK1, PTGS1 were found differentially expressed according to serum estradiol levels (FDR = 0. Three of these independently predicted estradiol levels in a multivariate model, as SCGB3A1 (HIN1 and TLN2 were up-regulated and PTGS1 (COX1 was down-regulated in breast samples from women with high serum estradiol. Serum estradiol, but none of the differentially expressed genes were significantly associated with mammographic density, another strong breast cancer risk factor. In breast carcinomas, expression of GREB1 and AREG was associated with serum estradiol in all cancers and in the subgroup of estrogen receptor positive cases. Conclusions We have identified genes associated with serum estradiol levels in normal breast tissue and in breast carcinomas. SCGB3A1 is a suggested tumor suppressor gene that inhibits cell growth and invasion and is methylated and down-regulated in many epithelial cancers. Our findings indicate this gene as an important inhibitor of breast cell proliferation in healthy women with high estradiol levels. In the breast, this gene is expressed in luminal cells only and is methylated in non-BRCA-related breast cancers. The possibility of a carcinogenic contribution of silencing of this gene for luminal, but not basal-like cancers should be further explored. PTGS1 induces prostaglandin E2 (PGE2 production which

  4. A feasibility study of soft embalmed human breast tissue for preclinical trials of HIFU- preliminary results

    Science.gov (United States)

    Joy, Joyce; Yang, Yang; Purdie, Colin; Eisma, Roos; Melzer, Andreas; Cochran, Sandy; Vinnicombe, Sarah

    2017-03-01

    Breast cancer is the commonest cancer in women in the UK, accounting for 30% of all new cancers in women, with an estimated 49,500 new cases in 20101. With the widespread negative publicity around over-diagnosis and over-treatment of low risk breast cancers, interest in the application of non-invasive treatments such as magnetic resonance imaging (MRI) guided high intensity focused ultrasound (HIFU) has increased. Development has begun of novel US transducers and platforms specifically designed for use with breast lesions, so as to improve the range of breast lesions that can be safely treated. However, before such transducers can be evaluated in patients in clinical trials, there is a need to establish their efficacy. A particular issue is the accuracy of temperature monitoring of FUS with MRI in the breast, since the presence of large amounts of surrounding fat can hinder temperature measurement. An appropriate anatomical model that imposes similar physical constraints to the breast and that responds to FUS in the same way would be extremely advantageous. The aim of this feasibility study is to explore the use of Thiel embalmed cadaveric tissue for these purposes. We report here the early results of laboratory-based experiments sonicating dissected breast samples from a Thiel embalmed soft human cadaver with high body mass index (BMI). A specially developed MRI compatible chamber and sample holder was developed to secure the sample and ensure reproducible sonications at the transducer focus. The efficacy of sonication was first studied with chicken breast and porcine tissue. The experiments were then repeated with the dissected fatty breast tissue samples from the soft-embalmed human cadavers. The sonicated Thiel breast tissue was examined histopathologically, which confirmed the absence of any discrete lesion. To investigate further, fresh chicken breast tissue was embalmed and the embalmed tissue was sonicated with the same parameters. The results confirmed the

  5. Multiple Pulses from Plasma Jets onto Liquid Covered Tissue

    Science.gov (United States)

    Norberg, Seth; Tian, Wei; Johnsen, Eric; Kushner, Mark J.

    2014-10-01

    Atmospheric pressure plasma jets are being studied in the treatment of biological surfaces that are often covered by a thin layer of liquid. The plume of the plasma jet contains neutral radicals and charged species that solvate into the liquid and eventually form terminal species that reach the tissue below. The contribution of neutral and charged species to reactivity in the liquid is sensitive to whether the active plasma plume touches the liquid. In this paper, we discuss results from modeling the production of the aqueous species formed from the interaction of the plume of plasma jets over multiple pulses with the water layer, and the fluences of the species to the underlying tissue. The model used in this study, nonPDPSIM, solves transport equations for charged and neutral species and electron energy, Poisson's equation for the electric potential, and Navier-Stokes equations for the neutral gas flow. Radiation transport includes photoionization of O2 and H2O in the gas and liquid phases and photodissocation of H2Oaq in the liquid. Multiple pulses when the plasma plume touches and does not touch the liquid will be examined. Two regimes of hydrodynamics will be discussed - low repetition rates where the neutral radicals are blown away before the next discharge pulse, and high repetition rate when the plasma plume interacts with neutral radicals from previous pulses. The density of aqueous ions produced in the liquid layer is strongly dependent on whether the plasma effluent touches or does not touch the water surface. Work supported by DOE Office of Fusion Energy Science and NSF.

  6. Detection of Slit2 promoter hypermethylation in tissue and serum samples from breast cancer patients.

    Science.gov (United States)

    Kim, Ga-Eon; Lee, Kyung Hwa; Choi, Yoo Duk; Lee, Ji Shin; Lee, Jae Hyuk; Nam, Jong Hee; Choi, Chan; Park, Min Ho; Yoon, Jung Han

    2011-10-01

    Promoter hypermethylation has been shown to be a common mechanism for inactivation of tumor suppressor genes in breast cancer. The aim of this study was to investigate the prevalence of Slit2 promoter hypermethylation in both the tumor and serum samples of breast cancer patients with ductal carcinoma in situ (DCIS) or invasive breast carcinoma (IBC). The methylation status of Slit2 was investigated in 210 tissue samples (15 breast with no pathological findings, 26 DCIS, and 169 IBC samples) and 123 corresponding serum samples (15 breast with no pathological findings, 26 DCIS, and 82 IBC samples) using methylation-specific polymerase chain reaction. Immunohistochemical staining for Slit2 was also performed using tissue microarray blocks to determine whether Slit2 promoter hypermethylation correlated with loss of Slit2 expression. Slit2 promoter hypermethylation was not detected in breast tissue and serum samples from patients with no pathological findings. DCIS or IBC showed a statistically higher frequency of Slit2 promoter hypermethylation compared to breast with no pathological findings in both the tissue and serum samples; however, there were no statistically significant differences between DCIS and IBC samples. Similar Slit2 promoter hypermethylation patterns were seen in the tissue samples and corresponding serum specimens (p Slit2 promoter hypermethylation was associated with loss of Slit2 expression. These results suggest that Slit2 promoter hypermethylation appears to be responsible for functionally silencing Slit2 expression. Slit2 promoter hypermethylation may be considered as a possible serum marker for early detection of breast cancer.

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

    Science.gov (United States)

    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.

  8. Study of effective atomic number of breast tissues determined using the elastic to inelastic scattering ratio

    Science.gov (United States)

    Antoniassi, M.; Conceição, A. L. C.; Poletti, M. E.

    2011-10-01

    In this work we have measured Compton and Rayleigh scattering radiation from normal (adipose and fibroglandular), benign (fibroadenoma) and malignant (ductal carcinoma) breast tissues using a monoenergetic beam of 17.44 keV and a scattering angle of 90° ( x=0.99 Å -1). A practical method using the area of Rayleigh and Compton scattering was used for determining the effective atomic number ( Zeff) of the samples, being validated through measurements of several reference materials. The results show that there are differences in the distributions of Zeff of breast tissues, which are mainly related to the elemental composition of carbon ( Z=6) and oxygen ( Z=8) of each tissue type. The results suggest that is possible to use the method to characterize the breast tissues permitting study histological features of the breast tissues related to their elemental composition.

  9. Study of effective atomic number of breast tissues determined using the elastic to inelastic scattering ratio

    Energy Technology Data Exchange (ETDEWEB)

    Antoniassi, M.; Conceicao, A.L.C. [Departamento de Fisica e Matematica, Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo (Brazil); Poletti, M.E., E-mail: poletti@ffclrp.usp.br [Departamento de Fisica e Matematica, Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo (Brazil)

    2011-10-01

    In this work we have measured Compton and Rayleigh scattering radiation from normal (adipose and fibroglandular), benign (fibroadenoma) and malignant (ductal carcinoma) breast tissues using a monoenergetic beam of 17.44 keV and a scattering angle of 90{sup o} (x=0.99 A{sup -1}). A practical method using the area of Rayleigh and Compton scattering was used for determining the effective atomic number (Z{sub eff}) of the samples, being validated through measurements of several reference materials. The results show that there are differences in the distributions of Z{sub eff} of breast tissues, which are mainly related to the elemental composition of carbon (Z=6) and oxygen (Z=8) of each tissue type. The results suggest that is possible to use the method to characterize the breast tissues permitting study histological features of the breast tissues related to their elemental composition.

  10. Aromatase overexpression in dysfunctional adipose tissue links obesity to postmenopausal breast cancer.

    Science.gov (United States)

    Wang, Xuyi; Simpson, Evan R; Brown, Kristy A

    2015-09-01

    The number of breast cancer cases has increased in the last a few decades and this is believed to be associated with the increased prevalence of obesity worldwide. The risk of breast cancer increases with age beyond menopause and the relationship between obesity and the risk of breast cancer in postmenopausal women is well established. The majority of postmenopausal breast cancers are estrogen receptor (ER) positive and estrogens produced in the adipose tissue promotes tumor formation. Obesity results in the secretion of inflammatory factors that stimulate the expression of the aromatase enzyme, which converts androgens into estrogens in the adipose tissue. Evidence demonstrating a link between obesity and breast cancer has led to the investigation of metabolic pathways as novel regulators of estrogen production, including pathways that can be targeted to inhibit aromatase specifically within the breast. This review aims to present some of the key findings in this regard. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. The distribution of tissue fibronectin and sialic acid in human breast cancer.

    Science.gov (United States)

    Süer, S; Baloğlu, H; Güngör, Z; Sönmez, H; Kökoğlu, E

    1998-06-01

    Our findings indicate that sialic acid and fibronectin levels in breast tumors are higher than those in normal tissues. The mean tissue fibronectin and sialic acid concentrations for patients with breast cancer were 30.90 +/- 9.68 microg/mg protein and 21.60 +/- 9.35 microg/mg protein, respectively, and for normal controls were 12.47 +/- 5.69 microg/mg protein, respectively. Tissue fibronectin and sialic acid can be important markers for human breast cancer.

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

    Science.gov (United States)

    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.

  13. Glandular breast tissue volume by magnetic resonance imaging in 100 healthy peripubertal girls

    DEFF Research Database (Denmark)

    Fugl, Louise; Hagen, Casper P; Mieritz, Mikkel G

    2016-01-01

    BACKGROUND: Appearance of glandular breast tissue may be difficult to distinguish from fat tissue by palpation, especially in obese girls. To our knowledge, validation of the clinical assessment of pubertal breast stages by magnetic resonance imaging (MRI) has never been performed. Our objective....... METHODS: Glandular breast tissue volume quantified by MRI and breast stage evaluation was performed in 100 healthy peripubertal girls. Circulating levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin B, and estradiol were measured by immunoassays. Ovarian volume, uterine volume....... The best parameters to distinguish prepubertal girls from girls with breast development were: LH (area under the curve (AUC) by receiver operating characteristic analysis = 0.871), inhibin B (AUC = 0.847) and estradiol (AUC = 0.830). CONCLUSION: Clinical palpation reliably detects the presence of glandular...

  14. A Cohort Study of p53 Mutations and Protein Accumulation in Benign Breast Tissue and Subsequent Breast Cancer Risk.

    Science.gov (United States)

    Kabat, Geoffrey C; Kandel, Rita A; Glass, Andrew G; Jones, Joan G; Olson, Neal; Duggan, Catherine; Ginsberg, Mindy; Negassa, Abdissa; Rohan, Thomas E

    2011-01-01

    Mutations in the p53 tumor suppressor gene and accumulation of its protein in breast tissue are thought to play a role in breast carcinogenesis. However, few studies have prospectively investigated the association of p53 immunopositivity and/or p53 alterations in women with benign breast disease in relation to the subsequent risk of invasive breast cancer. We carried out a case-control study nested within a large cohort of women biopsied for benign breast disease in order to address this question. After exclusions, 491 breast cancer cases and 471 controls were available for analysis. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). Neither p53 immunopositivity nor genetic alterations in p53 (either missense mutations or polymorphisms) was associated with altered risk of subsequent breast cancer. However, the combination of both p53 immunopositivity and any p53 nucleotide change was associated with an approximate 5-fold nonsignificant increase in risk (adjusted OR 4.79, 95% CI 0.28-82.31) but the confidence intervals were extremely wide. Our findings raise the possibility that the combination of p53 protein accumulation and the presence of genetic alterations may identify a group at increased risk of breast cancer.

  15. A Cohort Study of p53 Mutations and Protein Accumulation in Benign Breast Tissue and Subsequent Breast Cancer Risk

    Directory of Open Access Journals (Sweden)

    Geoffrey C. Kabat

    2011-01-01

    Full Text Available Mutations in the p53 tumor suppressor gene and accumulation of its protein in breast tissue are thought to play a role in breast carcinogenesis. However, few studies have prospectively investigated the association of p53 immunopositivity and/or p53 alterations in women with benign breast disease in relation to the subsequent risk of invasive breast cancer. We carried out a case-control study nested within a large cohort of women biopsied for benign breast disease in order to address this question. After exclusions, 491 breast cancer cases and 471 controls were available for analysis. Unconditional logistic regression was used to estimate odds ratios (OR and 95% confidence intervals (95% CI. Neither p53 immunopositivity nor genetic alterations in p53 (either missense mutations or polymorphisms was associated with altered risk of subsequent breast cancer. However, the combination of both p53 immunopositivity and any p53 nucleotide change was associated with an approximate 5-fold nonsignificant increase in risk (adjusted OR 4.79, 95% CI 0.28–82.31 but the confidence intervals were extremely wide. Our findings raise the possibility that the combination of p53 protein accumulation and the presence of genetic alterations may identify a group at increased risk of breast cancer.

  16. Application of the fractal Perlin noise algorithm for the generation of simulated breast tissue

    Science.gov (United States)

    Dustler, Magnus; Bakic, Predrag; Petersson, Hannie; Timberg, Pontus; Tingberg, Anders; Zackrisson, Sophia

    2015-03-01

    Software breast phantoms are increasingly seeing use in preclinical validation of breast image acquisition systems and image analysis methods. Phantom realism has been proven sufficient for numerous specific validation tasks. A challenge is the generation of suitably realistic small-scale breast structures that could further improve the quality of phantom images. Power law noise follows the noise power characteristics of breast tissue, but may not sufficiently represent certain (e.g., non-Gaussian) properties seen in clinical breast images. The purpose of this work was to investigate the utility of fractal Perlin noise in generating more realistic breast tissue through investigation of its power spectrum and visual characteristics. Perlin noise is an algorithm that creates smoothly varying random structures of an arbitrary frequency. Through the use of a technique known as fractal noise or fractional Brownian motion (fBm), octaves of noise with different frequency are combined to generate coherent noise with a broad frequency range. fBm is controlled by two parameters - lacunarity and persistence - related to the frequency and amplitude of successive octaves, respectively. Average noise power spectra were calculated and beta parameters estimated in sample volumes of fractal Perlin noise with different combinations of lacunarity and persistence. Certain combinations of parameters resulted in noise volumes with beta values between 2 and 3, corresponding to reported measurements in real breast tissue. Different combinations of parameters resulted in different visual appearances. In conclusion, Perlin noise offers a flexible tool for generating breast tissue with realistic properties.

  17. Using deep learning to segment breast and fibroglandular tissue in MRI volumes

    NARCIS (Netherlands)

    Dalmis, M.U.; Litjens, G.J.; Holland, K.; Setio, A.A.A.; Mann, R.M.; Karssemeijer, N.; Gubern Merida, A.

    2017-01-01

    PURPOSE: Automated segmentation of breast and fibroglandular tissue (FGT) is required for various computer-aided applications of breast MRI. Traditional image analysis and computer vision techniques, such atlas, template matching, or, edge and surface detection, have been applied to solve this task.

  18. Measurement of the linear attenuation coefficients of breast tissues by synchrotron radiation computed tomography

    Science.gov (United States)

    Chen, R. C.; Longo, R.; Rigon, L.; Zanconati, F.; De Pellegrin, A.; Arfelli, F.; Dreossi, D.; Menk, R.-H.; Vallazza, E.; Xiao, T. Q.; Castelli, E.

    2010-09-01

    The measurement of the linear attenuation coefficients of breast tissues is of fundamental importance in the field of breast x-ray diagnostic imaging. Different groups have evaluated the linear attenuation coefficients of breast tissues by carrying out direct attenuation measurements in which the specimens were thin and selected as homogeneous as possible. Here, we use monochromatic and high-intensity synchrotron radiation computed tomography (SR CT) to evaluate the linear attenuation coefficients of surgical breast tissues in the energy range from 15 to 26.5 keV. X-ray detection is performed by a custom digital silicon micro-strip device, developed in the framework of the PICASSO INFN experiment. Twenty-three human surgical breast samples were selected for SR CT and histological study. Six of them underwent CT, both as fresh tissue and after formalin fixation, while the remaining 17 were imaged only as formalin-fixed tissues. Our results for fat and fibrous tissues are in good agreement with the published values. However, in contrast to the published data, our measurements show no significant differences between fibrous and tumor tissues. Moreover, our results for fresh and formalin-fixed tissues demonstrate a reduction of the linear attenuation coefficient for fibrous and tumor tissues after fixation.

  19. Measurement of the linear attenuation coefficients of breast tissues by synchrotron radiation computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Chen, R C; Xiao, T Q [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai (China); Longo, R; Arfelli, F; Castelli, E [Department of Physics, University of Trieste, Trieste (Italy); Rigon, L; Dreossi, D; Menk, R-H; Vallazza, E [INFN, Sezione di Trieste, Trieste (Italy); Zanconati, F; De Pellegrin, A, E-mail: rongchang.chen@gmail.co [Department of Pathologic Anatomy, University of Trieste, Trieste (Italy)

    2010-09-07

    The measurement of the linear attenuation coefficients of breast tissues is of fundamental importance in the field of breast x-ray diagnostic imaging. Different groups have evaluated the linear attenuation coefficients of breast tissues by carrying out direct attenuation measurements in which the specimens were thin and selected as homogeneous as possible. Here, we use monochromatic and high-intensity synchrotron radiation computed tomography (SR CT) to evaluate the linear attenuation coefficients of surgical breast tissues in the energy range from 15 to 26.5 keV. X-ray detection is performed by a custom digital silicon micro-strip device, developed in the framework of the PICASSO INFN experiment. Twenty-three human surgical breast samples were selected for SR CT and histological study. Six of them underwent CT, both as fresh tissue and after formalin fixation, while the remaining 17 were imaged only as formalin-fixed tissues. Our results for fat and fibrous tissues are in good agreement with the published values. However, in contrast to the published data, our measurements show no significant differences between fibrous and tumor tissues. Moreover, our results for fresh and formalin-fixed tissues demonstrate a reduction of the linear attenuation coefficient for fibrous and tumor tissues after fixation.

  20. Raman microspectroscopy of Hematoporphyrins. Imaging of the noncancerous and the cancerous human breast tissues with photosensitizers

    Science.gov (United States)

    Brozek-Pluska, B.; Kopec, M.

    2016-12-01

    Raman microspectroscopy combined with fluorescence were used to study the distribution of Hematoporphyrin (Hp) in noncancerous and cancerous breast tissues. The results demonstrate the ability of Raman spectroscopy to distinguish between noncancerous and cancerous human breast tissue and to identify differences in the distribution and photodegradation of Hematoporphyrin, which is a photosensitizer in photodynamic therapy (PDT), photodynamic diagnosis (PDD) and photoimmunotherapy (PIT) of cancer. Presented results show that Hematoporphyrin level in the noncancerous breast tissue is lower compared to the cancerous one. We have proved also that the Raman intensity of lipids and proteins doesn't change dramatically after laser light irradiation, which indicates that the PDT treatment destroys preferably cancer cells, in which the photosensitizer is accumulated. The specific subcellular localization of photosensitizer for breast tissues samples soaked with Hematoporphyrin was not observed.

  1. Expression of proto-oncogene Fra-1 in human neoplastic breast tissues

    Institute of Scientific and Technical Information of China (English)

    Yuhua Song; Jing Wang; Xiaoyun Yu; Santai Song; Zefei Jiang

    2012-01-01

    Objective: Invasion and metastasis are the most significant and intrinsic biological characteristics of cancers, also which are main factors of malignant tumor causing treatment failure and death. Recent studies have found that Fra-1 plays an important role on cell migration, invasion, and maintaining malignant phenotype of transformed cells. But there are few studies about the expression and location of Fra-1 in breast tissues and cells being reported This study just aims to discuss the expression and location of transcription factor Fra-1 in benign and malignant human breast tissues. Methods: The expression of Fra-1 was investigated by immunohistochemistry in neoplastic breast diseases ranging from benign fibroadenoma to very aggressive undifferentiated carcinoma. The correlations of Fra-1 expression with other indicators of breast carcinoma prognosis (ER, PR and ErbB2 receptors) were analyzed. Results: All neoplastic breast tissues, either benign or malignant breast tissues, were nuclear immunoreactive for Fra-1-recognizing antibody. In 85% of benign tumors (17/20), the immunoreactive for Fra-1-recognizing antibody as exclusively restricted to the nuclei. In three cases (3/20,15%), focal unequivocal cytoplas-mic staining was also exhibited. Strong positive nuclear staining for Fra-1 was easily seen in all types of breast carcinomas. However the nuclear/cytoplasmic concomitant immunoreactivity was observed in all types of breast carcinomas. A clear shift in Fra-1 immunoreactivity, from an exclusively nuclear to a simultaneous nuclear and cytoplasmic localization was noticed in 90.2% (37/41) of breast carcinomas. No inverse relationship between Fra-1 and ER and PR protein levels was noticed in malignant tumors. The relative expression level of Fra-1 was not correlated with the expression of ErbB2. Conclusion: The overall expression, pattern and intensity of Fra-1 proteins were correlated with breast oncogenesis. Overexpression of Fra-1, leading to a persistent

  2. Identification of vitamin D3 target genes in human breast cancer tissue.

    Science.gov (United States)

    Sheng, Lei; Anderson, Paul H; Turner, Andrew G; Pishas, Kathleen I; Dhatrak, Deepak J; Gill, Peter G; Morris, Howard A; Callen, David F

    2016-11-01

    Multiple epidemiological studies have shown that high vitamin D3 status is strongly associated with improved breast cancer survival. To determine the molecular pathways influenced by 1 alpha, 25-dihydroxyvitamin D3 (1,25D) in breast epithelial cells we isolated RNA from normal human breast and cancer tissues treated with 1,25D in an ex vivo explant system. RNA-Seq revealed 523 genes that were differentially expressed in breast cancer tissues in response to 1,25D treatment, and 127 genes with altered expression in normal breast tissues. GoSeq KEGG pathway analysis revealed 1,25D down-regulated cellular metabolic pathways and enriched pathways involved with intercellular adhesion. The highly 1,25D up-regulated target genes CLMN, SERPINB1, EFTUD1, and KLK6were selected for further analysis and up-regulation by 1,25D was confirmed by qRT-PCR analysis in breast cancer cell lines and in a subset of human clinical samples from normal and cancer breast tissues. Ketoconazole potentiated 1,25D-mediated induction of CLMN, SERPINB1, and KLK6 mRNA through inhibition of 24-hydroxylase (CYP24A1) activity. Elevated expression levels of CLMN, SERPINB1, and KLK6 are associated with prolonged relapse-free survival for breast cancer patients. The major finding of the present study is that exposure of both normal and malignant breast tissue to 1,25D results in changes in cellular adhesion, metabolic pathways and tumor suppressor-like pathways, which support epidemiological data suggesting that adequate vitamin D3 levels may improve breast cancer outcome.

  3. TU-CD-207-01: Characterization of Breast Tissue Composition Using Spectral Mammography

    Energy Technology Data Exchange (ETDEWEB)

    Ding, H; Cho, H; Kumar, N; Sennung, D; Ng, A Lam; Molloi, S [Department of radiological scicens, University of California, Irvine, CA (United States)

    2015-06-15

    Purpose: To investigate the feasibility of characterizing the chemical composition of breast tissue, in terms of water and lipid, by using spectral mammography in simulation and postmortem studies. Methods: Analytical simulations were performed to obtain low- and high-energy signals of breast tissue based on previously reported water, lipid, and protein contents. Dual-energy decomposition was used to characterize the simulated breast tissue into water and lipid basis materials and the measured water density was compared to the known value. In experimental studies, postmortem breasts were imaged with a spectral mammography system based on a scanning multi-slit Si strip photon-counting detector. Low- and high-energy images were acquired simultaneously from a single exposure by sorting the recorded photons into the corresponding energy bins. Dual-energy material decomposition of the low- and high-energy images yielded individual pixel measurements of breast tissue composition in terms of water and lipid thicknesses. After imaging, each postmortem breast was chemically decomposed into water, lipid and protein. The water density calculated from chemical analysis was used as the reference gold standard. Correlation of the water density measurements between spectral mammography and chemical analysis was analyzed using linear regression. Results: Both simulation and postmortem studies showed good linear correlation between the decomposed water thickness using spectral mammography and chemical analysis. The slope of the linear fitting function in the simulation and postmortem studies were 1.15 and 1.21, respectively. Conclusion: The results indicate that breast tissue composition, in terms of water and lipid, can be accurately measured using spectral mammography. Quantitative breast tissue composition can potentially be used to stratify patients according to their breast cancer risk.

  4. The diagnostic capability of laser induced fluorescence in the characterization of excised breast tissues

    Science.gov (United States)

    Galmed, A. H.; Elshemey, Wael M.

    2017-08-01

    Differentiating between normal, benign and malignant excised breast tissues is one of the major worldwide challenges that need a quantitative, fast and reliable technique in order to avoid personal errors in diagnosis. Laser induced fluorescence (LIF) is a promising technique that has been applied for the characterization of biological tissues including breast tissue. Unfortunately, only few studies have adopted a quantitative approach that can be directly applied for breast tissue characterization. This work provides a quantitative means for such characterization via introduction of several LIF characterization parameters and determining the diagnostic accuracy of each parameter in the differentiation between normal, benign and malignant excised breast tissues. Extensive analysis on 41 lyophilized breast samples using scatter diagrams, cut-off values, diagnostic indices and receiver operating characteristic (ROC) curves, shows that some spectral parameters (peak height and area under the peak) are superior for characterization of normal, benign and malignant breast tissues with high sensitivity (up to 0.91), specificity (up to 0.91) and accuracy ranking (highly accurate).

  5. Effects of tissue heterogeneity on the optical estimate of breast density

    Science.gov (United States)

    Taroni, Paola; Pifferi, Antonio; Quarto, Giovanna; Spinelli, Lorenzo; Torricelli, Alessandro; Abbate, Francesca; Balestreri, Nicola; Ganino, Serena; Menna, Simona; Cassano, Enrico; Cubeddu, Rinaldo

    2012-01-01

    Breast density is a recognized strong and independent risk factor for developing breast cancer. At present, breast density is assessed based on the radiological appearance of breast tissue, thus relying on the use of ionizing radiation. We have previously obtained encouraging preliminary results with our portable instrument for time domain optical mammography performed at 7 wavelengths (635–1060 nm). In that case, information was averaged over four images (cranio-caudal and oblique views of both breasts) available for each subject. In the present work, we tested the effectiveness of just one or few point measurements, to investigate if tissue heterogeneity significantly affects the correlation between optically derived parameters and mammographic density. Data show that parameters estimated through a single optical measurement correlate strongly with mammographic density estimated by using BIRADS categories. A central position is optimal for the measurement, but its exact location is not critical. PMID:23082283

  6. Breast Tissue Composition and Immunophenotype and Its Relationship with Mammographic Density in Women at High Risk of Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Jia-Min B Pang

    Full Text Available To investigate the cellular and immunophenotypic basis of mammographic density in women at high risk of breast cancer.Mammograms and targeted breast biopsies were accrued from 24 women at high risk of breast cancer. Mammographic density was classified into Wolfe categories and ranked by increasing density. The histological composition and immunophenotypic profile were quantified from digitized haematoxylin and eosin-stained and immunohistochemically-stained (ERα, ERβ, PgR, HER2, Ki-67, and CD31 slides and correlated to mammographic density.Increasing mammographic density was significantly correlated with increased fibrous stroma proportion (rs (22 = 0.5226, p = 0.0088 and significantly inversely associated with adipose tissue proportion (rs (22 = -0.5409, p = 0.0064. Contrary to previous reports, stromal expression of ERα was common (19/20 cases, 95%. There was significantly higher stromal PgR expression in mammographically-dense breasts (p=0.026.The proportion of stroma and fat underlies mammographic density in women at high risk of breast cancer. Increased expression of PgR in the stroma of mammographically dense breasts and frequent and unexpected presence of stromal ERα expression raises the possibility that hormone receptor expression in breast stroma may have a role in mediating the effects of exogenous hormonal therapy on mammographic density.

  7. Breast Tissue Composition and Immunophenotype and Its Relationship with Mammographic Density in Women at High Risk of Breast Cancer.

    Science.gov (United States)

    Pang, Jia-Min B; Byrne, David J; Takano, Elena A; Jene, Nicholas; Petelin, Lara; McKinley, Joanne; Poliness, Catherine; Saunders, Christobel; Taylor, Donna; Mitchell, Gillian; Fox, Stephen B

    2015-01-01

    To investigate the cellular and immunophenotypic basis of mammographic density in women at high risk of breast cancer. Mammograms and targeted breast biopsies were accrued from 24 women at high risk of breast cancer. Mammographic density was classified into Wolfe categories and ranked by increasing density. The histological composition and immunophenotypic profile were quantified from digitized haematoxylin and eosin-stained and immunohistochemically-stained (ERα, ERβ, PgR, HER2, Ki-67, and CD31) slides and correlated to mammographic density. Increasing mammographic density was significantly correlated with increased fibrous stroma proportion (rs (22) = 0.5226, p = 0.0088) and significantly inversely associated with adipose tissue proportion (rs (22) = -0.5409, p = 0.0064). Contrary to previous reports, stromal expression of ERα was common (19/20 cases, 95%). There was significantly higher stromal PgR expression in mammographically-dense breasts (p=0.026). The proportion of stroma and fat underlies mammographic density in women at high risk of breast cancer. Increased expression of PgR in the stroma of mammographically dense breasts and frequent and unexpected presence of stromal ERα expression raises the possibility that hormone receptor expression in breast stroma may have a role in mediating the effects of exogenous hormonal therapy on mammographic density.

  8. System-wide Clinical Proteomics of Breast Cancer Reveals Global Remodeling of Tissue Homeostasis.

    Science.gov (United States)

    Pozniak, Yair; Balint-Lahat, Nora; Rudolph, Jan Daniel; Lindskog, Cecilia; Katzir, Rotem; Avivi, Camilla; Pontén, Fredrik; Ruppin, Eytan; Barshack, Iris; Geiger, Tamar

    2016-03-23

    The genomic and transcriptomic landscapes of breast cancer have been extensively studied, but the proteomes of breast tumors are far less characterized. Here, we use high-resolution, high-accuracy mass spectrometry to perform a deep analysis of luminal-type breast cancer progression using clinical breast samples from primary tumors, matched lymph node metastases, and healthy breast epithelia. We used a super-SILAC mix to quantify over 10,000 proteins with high accuracy, enabling us to identify key proteins and pathways associated with tumorigenesis and metastatic spread. We found high expression levels of proteins associated with protein synthesis and degradation in cancer tissues, accompanied by metabolic alterations that may facilitate energy production in cancer cells within their natural environment. In addition, we found proteomic differences between breast cancer stages and minor differences between primary tumors and their matched lymph node metastases. These results highlight the potential of proteomic technology in the elucidation of clinically relevant cancer signatures.

  9. Raising an Antibody Specific to Breast Cancer Subpopulations Using Phage Display on Tissue Sections

    DEFF Research Database (Denmark)

    Larsen, Simon Asbjørn; Meldgaard, Theresa; Fridriksdottir, Agla Jael Rubner

    2016-01-01

    BACKGROUND/AIM: Primary tumors display a great level of intra-tumor heterogeneity in breast cancer. The current lack of prognostic and predictive biomarkers limits accurate stratification and the ability to predict response to therapy. The aim of the present study was to select recombinant antibody...... fragments specific against breast cancer subpopulations, aiding the discovery of novel biomarkers. MATERIALS AND METHODS: Recombinant antibody fragments were selected by phage display. A novel shadowstick technology enabled the direct selection using tissue sections of antibody fragments specific against...... small subpopulations of breast cancer cells. Selections were performed against a subpopulation of breast cancer cells expressing CD271(+), as these previously have been indicated to be potential breast cancer stem cells. The selected antibody fragments were screened by phage ELISA on both breast cancer...

  10. Monoclonality and Genetic Instability in Premalignant Breast Tissue

    Science.gov (United States)

    2002-02-01

    and P. Devilee. Fractional allelic imbalance in human breast cancer increases with tetraploidization and chromosome loss. Int J Cancer 1992, 50: 544... hybridization . Cancer Genet Cytogenet 1999, 110: 94-102. 25. J. J. Going, H. M. Abd EI-Monem and J. A. Craft. Clonal origins of human breast cancer. J

  11. A novel plasma source for sterilization of living tissues

    Energy Technology Data Exchange (ETDEWEB)

    Martines, E; Zuin, M; Cavazzana, R; Gazza, E; Serianni, G; Spagnolo, S; Spolaore, M [Consorzio RFX, Associazione Euratom-ENEA sulla Fusione, Padova (Italy); Leonardi, A; Deligianni, V [Department of Neuroscience, Ophthalmology Unit, University of Padova (Italy); Brun, P; Aragona, M [Department of Histology, Microbiology and Medical Biotechnology, Histology Unit, University of Padova (Italy); Castagliuolo, I; Brun, P [Department of Histology, Microbiology and Medical Biotechnology, Microbiology Unit, University of Padova (Italy)], E-mail: emilio.martines@igi.cnr.it

    2009-11-15

    A source for the production of low-power plasmas at atmospheric pressure, to be used for the nondamaging sterilization of living tissues, is presented. The source, powered by radiofrequency and working with a helium flow, has a specific configuration, studied to prevent the formation of electric arcs dangerous to living matter. It is capable of killing different types of bacteria with a decimal reduction time of 1-2 min; on the contrary, human cells such as conjunctival fibroblasts were found to be almost unharmed by the plasma. A high concentration of OH radicals, likely to be the origin of the sterilizing effect, is detected through their UV emission lines. The effect of the UV and the OH radicals on the fibroblasts was analysed and no significant effects were detected.

  12. Sclerotic fibroma (storiform collagenoma)-like stroma in a fibroadenoma of axillary accessory breast tissue.

    Science.gov (United States)

    Val-Bernal, José Fernando; González-Vela, María Carmen; De Grado, Mauricio; Garijo, María Francisca

    2012-08-01

    Accessory breast tissue is a subcutaneous remnant persisting after normal embryological development of the breast. It occurs most frequently in the axilla. Fibroadenomas in axillary breast tissue are rare. We report the case of a 29-year-old female patient who presented a fibroadenoma arising in the accessory breast tissue of the right axillary fossa. The neoplasm showed foci of sclerotic fibroma-like stroma. The patient had no signs of Cowden's syndrome. To the best of our knowledge, a lesion of this kind has not been previously reported. This stromal change suggests an uncommon involutional phase of the fibroadenoma with production of sclerotic and hypocellular collagen. The lesion should be differentiated from extraneural perineuroma, from the changes in fibroadenomas in Cowden's syndrome, from sclerosing lobular hyperplasia (fibroadenomatoid mastopathy) and from pseudoangiomatous stromal hyperplasia.

  13. Spatial and temporal age-related spectral alterations in benign human breast tissue

    Science.gov (United States)

    Theophilou, Georgios; Fogarty, Simon W.; Trevisan, Júlio; Strong, Rebecca J.; Heys, Kelly A.; Patel, Imran I.; Stringfellow, Helen F.; Martin-Hirsch, Pierre L.; Martin, Francis L.

    2016-02-01

    Epidemiological evidence suggests that cancers attributable to exogenous carcinogenic agents may appear decades after initiating exposures. Environmental factors including lifestyle and/or diet have been implicated in the aetiology of breast cancer. Breast tissue undergoes continuous molecular and morphological changes from the time of thelarche to menopause and thereafter. These alterations are both cyclical and longitudinal, and can be influenced by several environmental factors including exposure to oestrogens. Research into the latent period leading to breast carcinogenesis has been mostly limited to when hyperplastic lesions are present. Investigations to identify a biomarker of commitment to disease in normal breast tissue are hindered by the molecular and histological diversity of disease-free breast tissue. Benign tissue from reduction mammoplasties provides an opportunity to study biochemical differences between women of similar ages as well as alterations with advancing age. Herein, synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy was used to examine the terminal ductal lobular epithelium (TDLU) and, intra- and inter-lobular epithelium to identify spatial and temporal changes within these areas. Principal component analysis (PCA) followed by linear discriminant analysis of mid-infrared spectra revealed unambiguous inter-individual as well as age-related differences in each histological compartment interrogated. Moreover, exploratory PCA of luminal and myoepithelial cells within the TDLU indicated the presence of specific cells, potentially stem cells. Understanding alterations within benign tissue may assist in the identification of alterations in latent pre-clinical stages of breast cancer.

  14. Efficacy of Tissue Tolerable Plasma (TTP against Ixodes ricinus

    Directory of Open Access Journals (Sweden)

    Bender, Claudia

    2014-03-01

    Full Text Available [english] The efficacy of Tissue Tolerable Plasma (TTP against ticks was tested, as data from the literature has demonstrated its efficacy against other acari.The study was carried out by using the KINPen09 (Argon as carrier gas on (n=24. Treatment times of 1 and 3 minutes led to a reversible inactivation of the ticks. After 5 min of treatment, they died.Thanks to the acaricidal effect of TPP, a new treatment strategy using the KINPen09 for tick-infested pets is now available.

  15. Associations of persistent organic pollutants in serum and adipose tissue with breast cancer prognostic markers

    Energy Technology Data Exchange (ETDEWEB)

    Arrebola, J.P., E-mail: jparrebola@ugr.es [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Virgen de las Nieves University Hospital, Radiation Oncology Department, Oncology Unit, Granada (Spain); CIBER en Epidemiología y Salud Pública (CIBERESP) (Spain); Fernández-Rodríguez, M.; Artacho-Cordón, F. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); University of Granada, Radiology and Physical Medicine Department (Spain); Garde, C. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Perez-Carrascosa, F.; Linares, I.; Tovar, I. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Virgen de las Nieves University Hospital, Radiation Oncology Department, Oncology Unit, Granada (Spain); González-Alzaga, B. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Escuela Andaluza de Salud Pública, Granada (Spain); Expósito, J. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Virgen de las Nieves University Hospital, Radiation Oncology Department, Oncology Unit, Granada (Spain); Torne, P. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); and others

    2016-10-01

    This study aimed to evaluate associations between exposure to a group of persistent organic pollutants, measured in both adipose tissue and serum samples from breast cancer patients, and a set of tumor prognostic markers. The study population comprised 103 breast cancer patients recruited in Granada, Southern Spain. Data for tumor prognostic markers were retrieved from hospital clinical records and socio-demographic information was gathered by questionnaire. Persistent organic pollutants were quantified by gas chromatography with electron capture detection. Exposure levels were categorized in quartiles, and associations were evaluated using unconditional logistic regression. Adipose tissue HCB concentrations were associated positively with ER and PR expression (p-trends = 0.044 and 0.005, respectively) and negatively with E-Cadherin and p53 expression (p-trends = 0.012 and 0.027, respectively). PCB-180 adipose tissue concentrations were positively associated with HER2 expression (p-trend = 0.036). Serum PCB-138 concentrations were positively associated with ER and PR expression (p-trends = 0.052 and 0.042, respectively). The risk of p53 expression was higher among women in the lowest quartile of serum PCB-138 concentrations, but no significant trend was observed (p-trend = 0.161). These findings indicate that human exposure to certain persistent organic pollutants might be related to breast cancer aggressiveness. We also highlight the influence on exposure assessment of the biological matrix selected, given that both serum and adipose tissue might yield relevant information on breast cancer prognosis. - Highlights: • The role of POP exposure on the pathogenesis breast cancer is still controversial. • POPs were analyzed in serum and adipose tissue from breast cancer patients. • POP concentrations were associated with breast cancer prognostic markers. • POPs in serum and adipose tissue of breast cancer patients may provide different clues.

  16. Tissue microarrays for testing basal biomarkers in familial breast cancer cases

    Directory of Open Access Journals (Sweden)

    Rozany Mucha Dufloth

    Full Text Available CONTEXT AND OBJECTIVE: The proteins p63, p-cadherin and CK5 are consistently expressed by the basal and myoepithelial cells of the breast, although their expression in sporadic and familial breast cancer cases has yet to be fully defined. The aim here was to study the basal immunopro-file of a breast cancer case series using tissue microarray technology. DESIGN AND SETTING: This was a cross-sectional study at Universidade Estadual de Campinas, Brazil, and the Institute of Pathology and Mo-lecular Immunology, Porto, Portugal. METHODS: Immunohistochemistry using the antibodies p63, CK5 and p-cadherin, and also estrogen receptor (ER and Human Epidermal Receptor Growth Factor 2 (HER2, was per-formed on 168 samples from a breast cancer case series. The criteria for identifying women at high risk were based on those of the Breast Cancer Linkage Consortium. RESULTS: Familial tumors were more frequently positive for the p-cadherin (p = 0.0004, p63 (p < 0.0001 and CK5 (p < 0.0001 than was sporadic cancer. Moreover, familial tumors had coexpression of the basal biomarkers CK5+/ p63+, grouped two by two (OR = 34.34, while absence of coexpression (OR = 0.13 was associ-ated with the sporadic cancer phenotype. CONCLUSION: Familial breast cancer was found to be associated with basal biomarkers, using tissue microarray technology. Therefore, characterization of the familial breast cancer phenotype will improve the understanding of breast carcinogenesis.

  17. Sterilizing tissue-materials using pulsed power plasma.

    Science.gov (United States)

    Heidarkhan Tehrani, Ashkan; Davari, Pooya; Singh, Sanjleena; Oloyede, Adekunle

    2014-04-01

    This paper investigates the potential of pulsed power to sterilize hard and soft tissues and its impact on their physico-mechanical properties. It hypothesizes that pulsed plasma can sterilize both vascular and avascular tissues and the transitive layers in between without deleterious effects on their functional characteristics. Cartilage/bone laminate was chosen as a model to demonstrate the concept, treated at low temperature, at atmospheric pressure, in short durations and in buffered environment using a purposed-built pulsed power unit. Input voltage and time of exposure were assigned as controlling parameters in a full factorial design of experiment to determine physical and mechanical alteration pre- and post-treatment. The results demonstrated that, discharges of 11 kV sterilized samples in 45 s, reducing intrinsic elastic modules from 1.4 ± 0.9 to 0.9 ± 0.6 MPa. There was a decrease of 14.1 % in stiffness and 27.8 % in elastic-strain energy for the top quartile. Mechanical impairment was directly proportional to input voltage (P value connective tissues with varying level of loss in mechanical robustness which we argue to be acceptable in certain medical and tissue engineering application.

  18. Fucosyltransferase 8 expression in breast cancer patients: A high throughput tissue microarray analysis.

    Science.gov (United States)

    Yue, Liling; Han, Cuicui; Li, Zubin; Li, Xin; Liu, Deshui; Liu, Shulin; Yu, Haitao

    2016-05-01

    The aim of this study was to compare the expression of fucosyltransferase 8 (FUT8) in breast cancer tissue and to investigate the relationship between this marker with tumor progression and its applicability to differential diagnosis. An immunohistochemical study was performed for FUT8 using the tissue microarray technique. In addition, the mRNA and protein levels of FUT8 in the tissue were also tested by real-time PCR and Western blot. There was a significant difference in cytoplasmic expression of FUT8 between breast cancer tissue and matched normal tissue (ptissues ranging from negative, weak positive, positive and strong positive were 2.7%, 40.2%, 54% and 3.2%, respectively. High FUT8 protein expression correlated with lymphatic metastasis (p=0.008) and with stage status (p=0.039). We detected that reduced FUT8 expression correlated with disease-free survival (p=0.02) and overall survival (p=0.04) of breast cancer patients. Expression of FUT8 can stratify breast cancer tissue and may be considered a prognostic marker for breast cancer patients.

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

    LENUS (Irish Health Repository)

    Ryan, James

    2011-01-01

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

  20. Identification and prognostic value of anterior gradient protein 2 expression in breast cancer based on tissue microarray.

    Science.gov (United States)

    Guo, Jilong; Gong, Guohua; Zhang, Bin

    2017-07-01

    Breast cancer has attracted substantial attention as one of the major cancers causing death in women. It is crucial to find potential biomarkers of prognostic value in breast cancer. In this study, the expression pattern of anterior gradient protein 2 in breast cancer was identified based on the main molecular subgroups. Through analysis of 69 samples from the Gene Expression Omnibus database, we found that anterior gradient protein 2 expression was significantly higher in non-triple-negative breast cancer tissues compared with normal tissues and triple-negative breast cancer tissues (p tissues. Anterior gradient protein 2 was significantly highly expressed in non-triple-negative breast cancer (grade 3 excluded) and non-triple-negative breast cancer tissues compared with triple-negative breast cancer tissues (p tissues compared with grade 3 tissues (p < 0.05). Analysis by Fisher's exact test revealed that anterior gradient protein 2 expression was significantly associated with histologic type, histological grade, oestrogen status and progesterone status. Univariate analysis of clinicopathological variables showed that anterior gradient protein 2 expression, tumour size and lymph node status were significantly correlated with overall survival in patients with grade 1 and 2 tumours. Cox multivariate analysis revealed anterior gradient protein 2 as a putative independent indicator of unfavourable outcomes (p = 0.031). All these data clearly showed that anterior gradient protein 2 is highly expressed in breast cancer and can be regarded as a putative biomarker for breast cancer prognosis.

  1. Computerized prediction of breast cancer risk: comparison between the global and local bilateral mammographic tissue asymmetry

    Science.gov (United States)

    Wang, Xingwei; Lederman, Dror; Tan, Jun; Wang, Xiao Hui; Zheng, Bin

    2011-03-01

    We have developed and preliminarily tested a new breast cancer risk prediction model based on computerized bilateral mammographic tissue asymmetry. In this study, we investigated and compared the performance difference of our risk prediction model when the bilateral mammographic tissue asymmetrical features were extracted in two different methods namely (1) the entire breast area and (2) the mirror-matched local strips between the left and right breast. A testing dataset including bilateral craniocaudal (CC) view images of 100 negative and 100 positive cases for developing breast abnormalities or cancer was selected from a large and diverse full-field digital mammography (FFDM) image database. To detect bilateral mammographic tissue asymmetry, a set of 20 initial "global" features were extracted from the entire breast areas of two bilateral mammograms in CC view and their differences were computed. Meanwhile, a pool of 16 local histogram-based statistic features was computed from eight mirror-matched strips between the left and right breast. Using a genetic algorithm (GA) to select optimal features, two artificial neural networks (ANN) were built to predict the risk of a test case developing cancer. Using the leave-one-case-out training and testing method, two GAoptimized ANNs yielded the areas under receiver operating characteristic (ROC) curves of 0.754+/-0.024 (using feature differences extracted from the entire breast area) and 0.726+/-0.026 (using the feature differences extracted from 8 pairs of local strips), respectively. The risk prediction model using either ANN is able to detect 58.3% (35/60) of cancer cases 6 to 18 months earlier at 80% specificity level. This study compared two methods to compute bilateral mammographic tissue asymmetry and demonstrated that bilateral mammographic tissue asymmetry was a useful breast cancer risk indicator with high discriminatory power.

  2. Aluminium and breast cancer: Sources of exposure, tissue measurements and mechanisms of toxicological actions on breast biology.

    Science.gov (United States)

    Darbre, Philippa D; Mannello, Ferdinando; Exley, Christopher

    2013-11-01

    This review examines recent evidence linking exposure to aluminium with the aetiology of breast cancer. The human population is exposed to aluminium throughout daily life including through diet, application of antiperspirants, use of antacids and vaccination. Aluminium has now been measured in a range of human breast structures at higher levels than in blood serum and experimental evidence suggests that the tissue concentrations measured have the potential to adversely influence breast epithelial cells including generation of genomic instability, induction of anchorage-independent proliferation and interference in oestrogen action. The presence of aluminium in the human breast may also alter the breast microenvironment causing disruption to iron metabolism, oxidative damage to cellular components, inflammatory responses and alterations to the motility of cells. The main research need is now to investigate whether the concentrations of aluminium measured in the human breast can lead in vivo to any of the effects observed in cells in vitro and this would be aided by the identification of biomarkers specific for aluminium action. © 2013.

  3. X-ray phase contrast imaging of the breast: Analysis of tissue simulating materials

    Energy Technology Data Exchange (ETDEWEB)

    Vedantham, Srinivasan; Karellas, Andrew [Department of Radiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655 (United States)

    2013-04-15

    Purpose: Phase contrast imaging, particularly of the breast, is being actively investigated. The purpose of this work is to investigate the x-ray phase contrast properties of breast tissues and commonly used breast tissue substitutes or phantom materials with an aim of determining the phantom materials best representative of breast tissues. Methods: Elemental compositions of breast tissues including adipose, fibroglandular, and skin were used to determine the refractive index, n= 1 -{delta}+i {beta}. The real part of the refractive index, specifically the refractive index decrement ({delta}), over the energy range of 5-50 keV were determined using XOP software (version 2.3, European Synchrotron Radiation Facility, France). Calcium oxalate and calcium hydroxyapatite were considered to represent the material compositions of microcalcifications in vivo. Nineteen tissue substitutes were considered as possible candidates to represent adipose tissue, fibroglandular tissue and skin, and four phantom materials were considered as possible candidates to represent microcalcifications. For each material, either the molecular formula, if available, or the elemental composition based on weight fraction, was used to determine {delta}. At each x-ray photon energy, the absolute percent difference in {delta} between the breast tissue and the substitute material was determined, from which three candidates were selected. From these candidate tissue substitutes, the material that minimized the absolute percent difference in linear attenuation coefficient {mu}, and hence {beta}, was considered to be best representative of that breast tissue. Results: Over the energy range of 5-50 keV, while the {delta} of CB3 and fibroglandular tissue-equivalent material were within 1% of that of fibroglandular tissue, the {mu} of fibroglandular tissue-equivalent material better approximated the fibroglandular tissue. While the {delta} of BR10 and adipose tissue-equivalent material were within 1% of

  4. TU-F-18C-01: Breast Tissue Decomposition Using Spectral CT After Distortion Correction

    Energy Technology Data Exchange (ETDEWEB)

    Ding, H; Zhao, B; Klopfer, M; Masaki, F; Baturin, P; Molloi, S [University of California, Irvine, CA (United States)

    2014-06-15

    Purpose: To investigate the feasibility of accurate breast tissue compositional characterization by using spectral-distortion-corrected dual energy images from a photon-counting spectral CT. Methods: Thirty eight postmortem breasts were imaged with a Cadmium-Zinc-Telluride (CZT)-based photon-counting spectral CT system at beam energy of 100 kVp. The energy-resolved detector sorted photons into low and high energy bins with a splitting energy of 42 keV. The estimated mean glandular dose (MGD) for each breast was approximately 2.0 mGy. Dual energy technique was used to decompose breast tissue into water, lipid, and protein contents. Two image-based methods were investigated to improve the accuracy of tissue compositional characterization. The first method simply limited the recorded spectra up to 90 keV. This reduced the pulse pile-up artifacts but it has some dose penalty. The second method corrected the spectral information of all measured photons by using a spectral distortion correction technique. Breasts were then chemically decomposed into their respective water, lipid, and protein contents, which was used as the reference standard. The accuracy of the tissue compositional measurement with spectral CT was evaluated by the root-mean-square (RMS) errors in percentage composition. Results: The errors in quantitative material decomposition were significantly reduced after the appropriate image processing methods. As compared to the chemical analysis as the reference standard, the averages of the RMS errors were estimated to be 15.5%, 3.3%, and 2.8% for the raw, energy-limited, and spectral-corrected images, respectively. Conclusion: Spectral CT can be used to accurately quantify the water, lipid, and protein contents in breast tissues by implementing a spectral distortion correction algorithm. The tissue compositional information can potentially improve the sensitivity and specificity for breast cancer diagnosis.

  5. Wide-field imaging of fluorescent deoxy-glucose in ex vivo malignant and normal breast tissue

    Science.gov (United States)

    Langsner, R. J.; Middleton, L. P.; Sun, J.; Meric-Bernstam, F.; Hunt, K. K.; Drezek, R. A.; Yu, T. K.

    2011-01-01

    Rapid in situ determination of surgical resection margins during breast cancer surgery would reduce patient time under anesthesia. We present preliminary data supporting the use of a fluorescent glucose analog (2-NBDG) as an optical contrast agent to differentiate freshly excised breast tissue containing cancerous cells from normal breast tissue. Multi-spectral images of 14 breast cancer specimens acquired before and after incubation with 2-NBDG demonstrated increased fluorescent signal in all of the malignant tissue due to increased 2-NBDG consumption. We demonstrate that 2-NBDG has potential as an optical contrast agent to differentiate cancerous from non-cancerous tissue. PMID:21698015

  6. Locomotor proteins in tissues of primary tumors and metastases of ovarian and breast cancer

    Science.gov (United States)

    Kondakova, I. V.; Yunusova, N. V.; Spirina, L. V.; Shashova, E. E.; Kolegova, E. S.; Kolomiets, L. A.; Slonimskaya, E. M.; Villert, A. B.

    2016-08-01

    The paper discusses the capability for active movement in an extracellular matrix, wherein remodeling of the cytoskeleton by actin binding proteins plays a significant role in metastases formation. We studied the expression of actin binding proteins and β-catenin in tissues of primary tumors and metastases of ovarian and breast cancer. Contents of p45 Ser β-catenin and the actin severing protein gelsolin were decreased in metastases of ovarian cancer relative to primary tumors. The level of the cofilin, functionally similar to gelsolin, was significantly higher in metastases compared to primary ovarian and breast tumor tissue. In breast cancer, significant increase in the number of an actin monomer binder protein thymosin-β4 was observed in metastases as compared to primary tumors. The data obtained suggest the involvement of locomotor proteins in metastases formation in ovarian and breast cancer.

  7. When fat becomes an ally of the enemy: adipose tissue as collaborator in human breast cancer.

    Science.gov (United States)

    Lapeire, Lore; Denys, Hannelore; Cocquyt, Véronique; De Wever, Olivier

    2015-07-01

    Since the discovery of leptin in 1994, our vision of adipose tissue as a static organ regulating mainly lipid storage and release has been completely overthrown, and adipose tissue is now seen as an active and integral organ in human physiology. In the past years, extensive research has tremendously given us more insights in the mechanisms and pathways involved not only in normal but also in 'sick' adipose tissue, for example, in obesity and lipodystrophy. With growing evidence of a link between obesity and several types of cancer, research focusing on the interaction between adipose tissue and cancer has begun to unravel the interesting but complex multi-lateral communication between the different players. With breast cancer as one of the first cancer types where a positive correlation between obesity and breast cancer incidence and prognosis in post-menopausal women was found, we have focused this review on the paracrine and endocrine role of adipose tissue in breast cancer initiation and progression. As important inter-species differences in adipose tissue occur, we mainly selected human adipose tissue- and breast cancer-based studies with a short reflection on therapeutic possibilities. This review is part of the special issue on "Adiposopathy in Cancer and (Cardio)Metabolic Diseases".

  8. Breast tissue classification in digital tomosynthesis images based on global gradient minimization and texture features

    Science.gov (United States)

    Qin, Xulei; Lu, Guolan; Sechopoulos, Ioannis; Fei, Baowei

    2014-03-01

    Digital breast tomosynthesis (DBT) is a pseudo-three-dimensional x-ray imaging modality proposed to decrease the effect of tissue superposition present in mammography, potentially resulting in an increase in clinical performance for the detection and diagnosis of breast cancer. Tissue classification in DBT images can be useful in risk assessment, computer-aided detection and radiation dosimetry, among other aspects. However, classifying breast tissue in DBT is a challenging problem because DBT images include complicated structures, image noise, and out-of-plane artifacts due to limited angular tomographic sampling. In this project, we propose an automatic method to classify fatty and glandular tissue in DBT images. First, the DBT images are pre-processed to enhance the tissue structures and to decrease image noise and artifacts. Second, a global smooth filter based on L0 gradient minimization is applied to eliminate detailed structures and enhance large-scale ones. Third, the similar structure regions are extracted and labeled by fuzzy C-means (FCM) classification. At the same time, the texture features are also calculated. Finally, each region is classified into different tissue types based on both intensity and texture features. The proposed method is validated using five patient DBT images using manual segmentation as the gold standard. The Dice scores and the confusion matrix are utilized to evaluate the classified results. The evaluation results demonstrated the feasibility of the proposed method for classifying breast glandular and fat tissue on DBT images.

  9. A Prospective Analysis of Dynamic Loss of Breast Projection in Tissue Expander-Implant Reconstruction

    Directory of Open Access Journals (Sweden)

    Lauren M Mioton

    2015-05-01

    Full Text Available BackgroundBreast projection is a critical element of breast reconstruction aesthetics, but little has been published regarding breast projection as the firm expander is changed to a softer implant. Quantitative data representing this loss in projection may enhance patient education and improve our management of patient expectations.MethodsFemale patients who were undergoing immediate tissue-expander breast reconstruction with the senior author were enrolled in this prospective study. Three-dimensional camera software was used for all patient photographs and data analysis. Projection was calculated as the distance between the chest wall and the point of maximal projection of the breast form. Values were calculated for final tissue expander expansion and at varying intervals 3, 6, and 12 months after implant placement.ResultsFourteen breasts from 12 patients were included in the final analysis. Twelve of the 14 breasts had a loss of projection at three months following the implant placement or beyond. The percentage of projection lost in these 12 breasts ranged from 6.30% to 43.4%, with an average loss of projection of 21.05%.ConclusionsThis study is the first prospective quantitative analysis of temporal changes in breast projection after expander-implant reconstruction. By prospectively capturing projection data with three-dimensional photographic software, we reveal a loss of projection in this population by three months post-implant exchange. These findings will not only aid in managing patient expectations, but our methodology provides a foundation for future objective studies of the breast form.

  10. Plasma transforming growth factor beta levels in breast cancer patients

    NARCIS (Netherlands)

    Sminia, P; Barten, AD; Van Waarde, MAWH; Vujaskovic, Z; Van Tienhoven, G

    1998-01-01

    We investigated whether the concentration of circulating transforming growth factor beta (TGF beta) yields diagnostic value in breast cancer. Blood was collected from twenty stage I and II breast cancer patients both prior to treatment and after surgical excision of the tumour. Both latent and activ

  11. Breast implant rupture and connective tissue disease: a review of the literature

    DEFF Research Database (Denmark)

    Hölmich, Lisbet Rosenkrantz; Lipworth, Loren; McLaughlin, Joseph K

    2007-01-01

    Large-scale epidemiologic studies to date have not found any credible association between silicone breast implants and either well-defined connective tissue diseases or undefined or atypical connective tissue diseases. It has been hypothesized that implant rupture could prompt an immunologic...... reaction giving rise to autoimmune or related diseases. In this article, the authors review the available literature on implant ruptures and connective tissue disease....

  12. Label-free imaging of human breast tissues using coherent anti-Stokes Raman scattering microscopy

    Science.gov (United States)

    Yang, Yaliang; Gao, Liang; Wang, Zhiyong; Thrall, Michael J.; Luo, Pengfei; Wong, Kelvin K.; Wong, Stephen T.

    2011-03-01

    Breast cancer is a common disease in women. Current imaging and diagnostic methods for breast cancer confront several limitations, like time-consuming, invasive and with a high cost. Alternative strategies are in high demand to alleviate patients' trauma and lower medical expenses. Coherent anti-Stokes Raman scattering (CARS) imaging technique offers many advantages, including label-free, sub-wavelength spatial resolution and video-rate imaging speed. Therefore, it has been demonstrated as a powerful tool for various biomedical applications. In this study, we present a label-free fast imaging method to identify breast cancer and its subtypes using CARS microscopy. Human breast tissues, including normal, benign and invasive carcinomas, were imaged ex vivo using a custom-built CARS microscope. Compared with results from corresponding hematoxylin and eosin (H&E) stains, the CARS technique has demonstrated its capability in identifying morphological features in a similar way as in H&E stain. These features can be used to distinguish breast cancer from normal and benign tissues, and further separate cancer subtypes from each other. Our pilot study suggests that CARS microscopy could be used as a routine examination tool to characterize breast cancer ex vivo. Moreover, its label-free and fast imaging properties render this technique as a promising approach for in vivo and real-time imaging and diagnosis of breast cancer.

  13. Selection of a breast cancer subpopulation-specific antibody using phage display on tissue sections

    DEFF Research Database (Denmark)

    Larsen, Simon Asbjørn; Meldgaard, Theresa; Fridriksdottir, Agla J

    2015-01-01

    Breast cancer tumors are composed of heterogeneous cell populations. These populations display a high variance in morphology, growth and metastatic propensity. They respond differently to therapeutic interventions, and some may be more prone to cause recurrence. Studying individual subpopulations...... stem cells. We isolated an antibody fragment LH 7, which in immunohistochemistry experiments demonstrates specific binding to breast cancer subpopulations. The selection of antibody fragments directly on small defined areas within a larger section of malignant tissue is a novel approach by which...... has the potential to provide new insight and treatment strategies for breast cancer....

  14. The Role of Heavy Metal Salts in Pathological Biomineralization of Breast Cancer Tissue.

    Science.gov (United States)

    Romanjuk, Anatolij; Lyndin, Mykola; Moskalenko, Roman; Gortinskaya, Olena; Lyndina, Yuliya

    2016-01-01

    The process of pathological biomineralization plays an important part in the morphogenesis of tumors. The role of heavy metal salts in the pathological mineralization of breast cancer tissue should not be ruled out, considering their ability to enter into covalent bonds with calcium salt molecules. The aim of the study was to investigate the microelement composition of breast cancer calcifications and the participation of heavy metals in their formation process. The material for the study consisted of 20 specimens of breast cancer tissue in which calcifications had been found in histological tests (hematoxylin-eozin and alizarin red S staining). The chemical composition of the calcifications was studied using a scanning electron microscope with an energy-dispersive spectrometer. Alizarin red S staining detected the presence of concrements in tumor tissue and rings of calcification around these deposits. Examining the biomineralization with energy dispersive spectrometry showed that along with calcium and phosphorus, it contained microelements such as iron, zinc, copper, chromium and nickel, which can replace calcium ions in the exterior part of hydroxyapatite molecules. This causes the hydroxyapatite molecule's molar mass to increase and its solubility to decrease; its chances of being deposited in tumor tissue also increase. This implies that an increased intake of heavy metal salts in organisms can lead to pathological mineralization of breast cancer tissue. Excessive intake of heavy metal salts into the body leads to their involvement in the pathological mineralization of breast cancer tissue. This happens due to these salts bonding to hydroxyapatite molecules, direct sedimentation of proteins and increasing degenerative-necrotic changes in breast cancer tissue as the mineralization process progresses.

  15. Plasma mediated ablation of biological tissues with ultrashort laser pulses

    Energy Technology Data Exchange (ETDEWEB)

    Oraevsky, A.A. [Lawrence Livermore National Lab., CA (United States)]|[Rice Univ., Houston, TX (United States). Dept. of Electrical Engineering; DaSilva, L.B.; Feit, M.D. [Lawrence Livermore National Lab., CA (United States)] [and others

    1995-03-08

    Plasma mediated ablation of collagen gels and porcine cornea was studied at various laser pulse durations in the range from 350 fs to 1 ns at 1,053 nm wavelength. A time resolved stress detection technique was employed to measure transient stress profiles and amplitudes. Optical microscopy was used to characterize ablation craters qualitatively, while a wide band acoustic transducer helped to quantify tissue mechanical response and the ablation threshold. The ablation threshold was measured as a function of laser pulse duration and linear absorption coefficient. For nanosecond pulses the ablation threshold was found to have a strong dependence on the linear absorption coefficient of the material. As the pulse length decreased into the subpicosecond regime the ablation threshold became insensitive to the linear absorption coefficient. The ablation efficiency was found to be insensitive to both the laser pulse duration and the linear absorption coefficient. High quality ablation craters with no thermal or mechanical damage to surrounding material were obtained with 350 fs laser pulses. The mechanism of optical breakdown at the tissue surface was theoretically investigated. In the nanosecond regime, optical breakdown proceeds as an electron collisional avalanche ionization initiated by thermal seed electrons. These seed electrons are created by heating of the tissue by linear absorption. In the ultrashort pulse range, optical breakdown is initiated by the multiphoton ionization of the irradiated medium (6 photons in case of tissue irradiated at 1,053 nm wavelength), and becomes less sensitive to the linear absorption coefficient. The energy deposition profile is insensitive to both the laser pulse duration and the linear absorption coefficient.

  16. Tissue architecture and breast cancer: the role of extracellular matrix and steroid hormones

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, R K; Bissell, M J

    2000-06-01

    The changes in tissue architecture that accompany the development of breast cancer have been the focus of investigations aimed at developing new cancer therapeutics. As we learn more about the normal mammary gland, we have begun to understand the complex signaling pathways underlying the dramatic shifts in the structure and function of breast tissue. Integrin-, growth factor-, and steroid hormone-signaling pathways all play an important part in maintaining tissue architecture; disruption of the delicate balance of signaling results in dramatic changes in the way cells interact with each other and with the extracellular matrix, leading to breast cancer. The extracellular matrix itself plays a central role in coordinating these signaling processes. In this review, we consider the interrelationships between the extracellular matrix, integrins, growth factors, and steroid hormones in mammary gland development and function.

  17. [Concentration of cadmium in breast cancer tissue of women living in the Wielkopoiska region].

    Science.gov (United States)

    Rydzewska, Anna; Król, Iwona; Lipiński, Leszek

    2004-01-01

    The research was carried out concerning the contents of cadmium in breast cancer tissues in 52 women aged 35-81 years (x = 67.62 +/- 12.43) living in the Wielkopolska region. Particular concentrations of this metal in the range of 0.01-1.08 mg/g wet wt. (x = 0.13 +/- 0.18) were found in all the studied specimens. The obtained results were assessed regarding the women's place of residence--Kalisz, Leszno, Pila or Poznan voivodships--and a particular living area: an industrialised town, other towns or villages of the Wielkopolska region. A statistically significant difference in the content of cadmium in breast cancer tissues was found in women inhabiting the Poznan and Pila voivodships. Moreover, marked differences were observed between the average cadmium concentrations in the breast cancer tissue samples in women living in the remaining voivodships and the types of living areas.

  18. The elevated homocysteine stimulates changes of haemostatic function of plasma isolated from breast cancer patients.

    Science.gov (United States)

    Kedzierska, Magdalena; Malinowska, Joanna; Glowacki, Rafal; Olas, Beata; Bald, Edward; Jeziorski, Arkadiusz; Piekarski, Janusz

    2011-09-01

    The aim of our study was to explain the effect of elevated homocysteine (measured by HPLC) on haemostatic activity of plasma from breast cancer patients (fibrin polymerization and lysis; the thrombin and prothrombin time), because homocysteine (Hcys) induces changes in haemostasis, as well blood clotting as fibrinolysis. Patients were hospitalized in Department of Oncological Surgery, Medical University of Lodz, Poland. All patients have not had preadjuvant therapy, and samples from patients were taken before surgery. We observed that changes of selected parameters of haemostatic properties of plasma, e.g., the prothrombin time and thrombin time were prolonged in plasma from invasive breast cancer when compared with the control group (healthy subjects) and patients with benign breast diseases. Our results showed also that the correlation between the increased amount of Hcys and changes of selected parameters of haemostasis in invasive breast cancer patients exists. Considering the data presented in this study, we suggest that the elevated Hcys in invasive breast cancer patients may induce the changes of haemostatic properties of plasma isolated from these patients.

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

    Science.gov (United States)

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

    2016-12-01

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

  20. Quantitative breast tissue characterization using grating-based x-ray phase-contrast imaging

    Science.gov (United States)

    Willner, M.; Herzen, J.; Grandl, S.; Auweter, S.; Mayr, D.; Hipp, A.; Chabior, M.; Sarapata, A.; Achterhold, K.; Zanette, I.; Weitkamp, T.; Sztrókay, A.; Hellerhoff, K.; Reiser, M.; Pfeiffer, F.

    2014-04-01

    X-ray phase-contrast imaging has received growing interest in recent years due to its high capability in visualizing soft tissue. Breast imaging became the focus of particular attention as it is considered the most promising candidate for a first clinical application of this contrast modality. In this study, we investigate quantitative breast tissue characterization using grating-based phase-contrast computed tomography (CT) at conventional polychromatic x-ray sources. Different breast specimens have been scanned at a laboratory phase-contrast imaging setup and were correlated to histopathology. Ascertained tumor types include phylloides tumor, fibroadenoma and infiltrating lobular carcinoma. Identified tissue types comprising adipose, fibroglandular and tumor tissue have been analyzed in terms of phase-contrast Hounsfield units and are compared to high-quality, high-resolution data obtained with monochromatic synchrotron radiation, as well as calculated values based on tabulated tissue properties. The results give a good impression of the method’s prospects and limitations for potential tumor detection and the associated demands on such a phase-contrast breast CT system. Furthermore, the evaluated quantitative tissue values serve as a reference for simulations and the design of dedicated phantoms for phase-contrast mammography.

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

    Science.gov (United States)

    2016-07-12

    Estrogen Receptor-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Progesterone Receptor-positive Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

  2. Regional spectroscopy of paraffin-embedded breast cancer tissue using pulsed terahertz transmission imaging

    Science.gov (United States)

    Bowman, Tyler; El-Shenawee, Magda; Campbell, Lucas

    2016-03-01

    This work seeks to obtain the properties of paraffin-embedded breast cancer tumor tissues using transmission imaging and spectroscopy. Formalin-fixed and paraffin-embedded breast tumors are first sectioned into slices of 20 μm and 30 μm and placed between two tsurupica slides. The slides are then scanned in a pulsed terahertz system using transmission imaging. The tissue regions in adjacent pathology section are compared to the transmission imaging scan in order to define a region of points over which to average the electrical properties results from the scan.

  3. Label-free discrimination of normal and fibroadenomal breast tissues using second harmonic generation imaging.

    Science.gov (United States)

    Zheng, Liqin; Zhuo, Shuangmu; Chen, Gang; Zhu, Xiaoqin; Jiang, Xingshan; Yan, Jun; Chen, Jianxin; Xie, Shusen

    2011-01-01

    Early detection of fibroadenoma (FA) is critical for preventing subsequent breast cancer. In this work, we show that label-free second harmonic generation (SHG) imaging is feasible and effective in quantitatively differentiating the fibroadenomal tissue from normal breast tissue. With the advent of the clinical portability of miniature SHG microscopy, we believe that the technique has great potential in offering a noninvasive in vivo imaging tool for early detection of FA and monitoring the treatment responses of FA in clinics. Copyright © 2011 Wiley Periodicals, Inc.

  4. Theoretical and Experimental Estimations of Volumetric Inductive Phase Shift in Breast Cancer Tissue

    Science.gov (United States)

    González, C. A.; Lozano, L. M.; Uscanga, M. C.; Silva, J. G.; Polo, S. M.

    2013-04-01

    Impedance measurements based on magnetic induction for breast cancer detection has been proposed in some studies. This study evaluates theoretical and experimentally the use of a non-invasive technique based on magnetic induction for detection of patho-physiological conditions in breast cancer tissue associated to its volumetric electrical conductivity changes through inductive phase shift measurements. An induction coils-breast 3D pixel model was designed and tested. The model involves two circular coils coaxially centered and a human breast volume centrally placed with respect to the coils. A time-harmonic numerical simulation study addressed the effects of frequency-dependent electrical properties of tumoral tissue on the volumetric inductive phase shift of the breast model measured with the circular coils as inductor and sensor elements. Experimentally; five female volunteer patients with infiltrating ductal carcinoma previously diagnosed by the radiology and oncology departments of the Specialty Clinic for Women of the Mexican Army were measured by an experimental inductive spectrometer and the use of an ergonomic inductor-sensor coil designed to estimate the volumetric inductive phase shift in human breast tissue. Theoretical and experimental inductive phase shift estimations were developed at four frequencies: 0.01, 0.1, 1 and 10 MHz. The theoretical estimations were qualitatively in agreement with the experimental findings. Important increments in volumetric inductive phase shift measurements were evident at 0.01MHz in theoretical and experimental observations. The results suggest that the tested technique has the potential to detect pathological conditions in breast tissue associated to cancer by non-invasive monitoring. Further complementary studies are warranted to confirm the observations.

  5. Plasma Cysteinylglycine Levels and Breast Cancer Risk in Women

    Science.gov (United States)

    Cysteinylglycine, a prooxidant generated during the catabolism of glutathione, has been suggested to induce oxidative stress and lipid peroxidation, leading to the development of human cancers. Observational data relating cysteinylglycine status to breast cancer risk are lacking. We prospectively ev...

  6. Breast Field Cancerization: Isolation and Comparison of Telomerase-Expressing Cells in Tumor and Tumor Adjacent, Histologically Normal Breast Tissue

    Science.gov (United States)

    Trujillo, Kristina A.; Hines, William C.; Vargas, Keith M.; Jones, Anna C.; Joste, Nancy E.; Bisoffi, Marco; Griffith, Jeffrey K.

    2011-01-01

    Telomerase stabilizes chromosomes by maintaining telomere length, immortalizes mammalian cells, and is expressed in more than 90% of human tumors. However, the expression of human telomerase reverse transcriptase (hTERT) is not restricted to tumor cells. We have previously shown that a subpopulation of human mammary epithelial cells (HMEC) in tumor-adjacent, histologically normal (TAHN) breast tissues expresses hTERT mRNA at levels comparable with levels in breast tumors. In the current study, we first validated a reporter for measuring levels of hTERT promoter activity in early-passage HMECs and then used this reporter to compare hTERT promoter activity in HMECs derived from tumor and paired TAHN tissues 1, 3, and 5 cm from the tumor (TAHN-1, TAHN-3, and TAHN-5, respectively). Cell sorting, quantitative real-time PCR, and microarray analyses showed that the 10% of HMECs with the highest hTERT promoter activity in both tumor and TAHN-1 tissues contain more than 95% of hTERT mRNA and overexpress many genes involved in cell cycle and mitosis. The percentage of HMECs within this subpopulation showing high hTERT promoter activity was significantly reduced or absent in TAHN-3 and TAHN-5 tissues. We conclude that the field of normal tissue proximal to the breast tumors contains a population of HMECs similar in hTERT expression levels and in gene expression to the HMECs within the tumor mass and that this population is significantly reduced in tissues more distal to the tumor. PMID:21775421

  7. Infrared imaging in breast cancer: automated tissue component recognition and spectral characterization of breast cancer cells as well as the tumor microenvironment.

    Science.gov (United States)

    Benard, Audrey; Desmedt, Christine; Smolina, Margarita; Szternfeld, Philippe; Verdonck, Magali; Rouas, Ghizlane; Kheddoumi, Naima; Rothé, Françoise; Larsimont, Denis; Sotiriou, Christos; Goormaghtigh, Erik

    2014-03-07

    Current evaluation of histological sections of breast cancer samples remains unsatisfactory. The search for new predictive and prognostic factors is ongoing. Infrared spectroscopy and its potential to probe tissues and cells at the molecular level without requirement for contrast agents could be an attractive tool for clinical and diagnostic analysis of breast cancer. In this study, we report the successful application of FTIR (Fourier transform infrared) imaging for breast tissue component characterization. We show that specific FTIR spectral signatures can be assigned to the major tissue components of breast tumor samples. We demonstrate that a tissue component classifier can be built based on a spectral database of well-annotated tissues and successfully validated on independent breast samples. We also demonstrate that spectral features can reveal subtle differences within a tissue component, capturing for instance lymphocytic and stromal activation. By investigating in parallel lymph nodes, tonsils and wound healing tissues, we prove the uniqueness of the signature of both lymphocytic infiltrate and tumor microenvironment in the breast disease context. Finally, we demonstrate that the biochemical information reflected in the epithelial spectra might be clinically relevant for the grading purpose, suggesting potential to improve breast cancer management in the future.

  8. Quantification of tissue inhibitor of metalloproteinases 2 in plasma from healthy donors and cancer patients

    DEFF Research Database (Denmark)

    Larsen, M. B.; Stephens, R. W.; Brünner, Nils;

    2005-01-01

    and optimized for measurement of TIMP-2 in plasma. The capturing antibody in the ELISA was a monoclonal, while the detecting antibody was a chicken polyclonal antibody recognizing the native form of human TIMP-2. The levels of TIMP-2 were measured in ethylenediaminetetraacetic acid (EDTA) and citrate plasma...... from healthy donors. The median values were determined as 163 ng/ml (n = 186) with a range of 109-253 ng/ml for EDTA plasma and 139 ng/ml (n = 77) with a range of 95-223 ng/ml for citrate plasma. The TIMP-2 concentration in citrate plasma from 15 patients with advanced, stage IV breast cancer had...... a median value of 160 ng/ml, only slightly higher but statistically distinguishable from the level found in citrate plasma from the healthy donors. In addition, the TIMP-2 concentration in EDTA plasma from colorectal cancer patients revealed a significantly higher level in plasma from patients with Dukes...

  9. Shear Wave Imaging of Breast Tissue by Color Doppler Shear Wave Elastography.

    Science.gov (United States)

    Yamakoshi, Yoshiki; Nakajima, Takahito; Kasahara, Toshihiro; Yamazaki, Mayuko; Koda, Ren; Sunaguchi, Naoki

    2017-02-01

    Shear wave elastography is a distinctive method to access the viscoelastic characteristic of the soft tissue that is difficult to obtain by other imaging modalities. This paper proposes a novel shear wave elastography [color Doppler shear wave imaging (CD SWI)] for breast tissue. Continuous shear wave is produced by a small lightweight actuator, which is attached to the tissue surface. Shear wave wavefront that propagates in tissue is reconstructed as a binary pattern that consists of zero and the maximum flow velocities on color flow image (CFI). Neither any modifications of the ultrasound color flow imaging instrument nor a high frame rate ultrasound imaging instrument is required to obtain the shear wave wavefront map. However, two conditions of shear wave displacement amplitude and shear wave frequency are needed to obtain the map. However, these conditions are not severe restrictions in breast imaging. This is because the minimum displacement amplitude is [Formula: see text] for an ultrasonic wave frequency of 12 MHz and the shear wave frequency is available from several frequencies suited for breast imaging. Fourier analysis along time axis suppresses clutter noise in CFI. A directional filter extracts shear wave, which propagates in the forward direction. Several maps, such as shear wave phase, velocity, and propagation maps, are reconstructed by CD SWI. The accuracy of shear wave velocity measurement is evaluated for homogeneous agar gel phantom by comparing with the acoustic radiation force impulse method. The experimental results for breast tissue are shown for a shear wave frequency of 296.6 Hz.

  10. Immunoreactive prolactin in breast milk and plasma of women with hyperprolactinemia, galactorrhea and menstrual dysfunction.

    Science.gov (United States)

    Yuen, B H

    1986-01-01

    Prolactin levels were measured by radioimmunoassay in paired breast milk and plasma samples of 11 hyperprolactinemic women with galactorrhea and various menstrual disorders (amenorrhea, n = 8; oligomenorrhea, n = 2; luteal phase defect, n = 1) before and during treatment with bromocriptine (Parlodel, Sandoz). Pretreatment levels of prolactin in the milk and plasma were 80 +/- 13 ng/mL (mean +/- SEM) and 47 +/- 7 ng/mL (P less than 0.05), respectively. While on treatment, the concentration gradient for prolactin remained in favour of the milk, with values for milk and plasma 59 +/- 11 and 29 +/- 3 ng/mL (P less than 0.01), respectively. Thus, bromocriptine lowered the prolactin concentrations in both breast milk and plasma. Since prolactin in milk is biologically active, these findings may be relevant to the initiation and maintenance of lactation in women with abnormal lactogenesis.

  11. Impact of Prior Tissue Expander/Implant on Postmastectomy Free Flap Breast Reconstruction.

    Science.gov (United States)

    Roostaeian, Jason; Yoon, Alfred P; Ordon, Shannon; Gold, Chris; Crisera, Christopher; Festekjian, Jaco; Da Lio, Andrew; Lipa, Joan E

    2016-04-01

    Implant-based breast reconstructions can result in unsatisfactory results requiring surgical revision or salvage reconstructive surgery with autologous tissue. This study compares the outcomes and complications of salvage (tertiary) flap reconstruction after failed prosthesis placement to those of primary/secondary flap reconstruction. All patients undergoing free flap breast reconstruction after failed prosthesis between July 1, 2005, and June 30, 2014, were identified. A matched number of patients who underwent a de novo free flap breast reconstruction were selected randomly for review. The indication for prosthesis removal, demographic and operative data, flap type and inset, and complication rates were evaluated. Eighty-nine women with a history of failed implant-based reconstruction required free flap reconstruction for salvage in 121 breasts. Capsular contracture was the most common indication for prosthesis removal (62.0 percent). Recipient vessel scarring was 5.23 times more likely to occur in the prior prosthesis group (p breast reconstruction with autologous tissue after failed prosthesis can be safely performed, with success rates similar to those of primary free flap breast reconstruction. However, these procedures may have increased complexity because of recipient vessel scarring, higher rates of prior radiation therapy, and major complications, which may warrant appropriate preoperative planning and patient counseling. Therapeutic, III.

  12. Plasma Biomarker Profiles Differ Depending on Breast Cancer Subtype but RANTES is Consistently Increased

    Energy Technology Data Exchange (ETDEWEB)

    Gonzales, Rachel M.; Daly, Don S.; Tan, Ruimin; Marks, Jeffrey R.; Zangar, Richard C.

    2011-07-01

    Background: Current biomarkers for breast cancer have little potential for detection. We determined if breast cancer subtypes influence circulating protein biomarkers. Methods: A sandwich-ELISA microarray platform was used to evaluate 23 candidate biomarkers in plasma samples that were obtained from subjects with either benign breast disease or invasive breast cancer. All plasma samples were collected at the time of biopsy, after a referral due to a suspicious screen (e.g., mammography). Cancer samples were evaluated based on breast cancer subtypes, as defined by the HER2 and estrogen receptor statuses. Results: Ten proteins were statistically altered in at least one breast cancer subtype, including four epidermal growth factor receptor ligands, two matrix metalloproteases, two cytokines, and two angiogenic factors. Only one cytokine, RANTES, was significantly increased (P<0.01 for each analysis) in all four subtypes, with areas under receiver operating characteristic curves (AUC) that ranged from 0.76 to 0.82, depending on cancer subtype. The best AUC values were observed for analyses that combined data from multiple biomarkers, with values ranging from 0.70 to 0.99, depending on the cancer subtype. Although the results for RANTES are consistent with previous publications, the multi-assay results need to be validated in independent sample sets. Conclusions: Different breast cancer subtypes produce distinct biomarker profiles, and circulating protein biomarkers have potential to differentiate between true and false positive screens for breast cancer. Impact: Subtype-specific biomarker panels may be useful for detecting breast cancer or as an adjunct assay to improve the accuracy of current screening methods.

  13. Comparison of breast tissue measurements using magnetic resonance imaging, digital mammography and a mathematical algorithm

    Science.gov (United States)

    Lu, Lee-Jane W.; Nishino, Thomas K.; Johnson, Raleigh F.; Nayeem, Fatima; Brunder, Donald G.; Ju, Hyunsu; Leonard, Morton H., Jr.; Grady, James J.; Khamapirad, Tuenchit

    2012-11-01

    Women with mostly mammographically dense fibroglandular tissue (breast density, BD) have a four- to six-fold increased risk for breast cancer compared to women with little BD. BD is most frequently estimated from two-dimensional (2D) views of mammograms by a histogram segmentation approach (HSM) and more recently by a mathematical algorithm consisting of mammographic imaging parameters (MATH). Two non-invasive clinical magnetic resonance imaging (MRI) protocols: 3D gradient-echo (3DGRE) and short tau inversion recovery (STIR) were modified for 3D volumetric reconstruction of the breast for measuring fatty and fibroglandular tissue volumes by a Gaussian-distribution curve-fitting algorithm. Replicate breast exams (N = 2 to 7 replicates in six women) by 3DGRE and STIR were highly reproducible for all tissue-volume estimates (coefficients of variation tissue, (2) 0.72-0.82, 0.64-0.96, and 0.77-0.91, for glandular volume, (3) 0.87-0.98, 0.94-1.07, and 0.89-0.99, for fat volume, and (4) 0.89-0.98, 0.94-1.00, and 0.89-0.98, for total breast volume. For all values estimated, the correlation was stronger for comparisons between the two MRI than between each MRI versus mammography, and between each MRI versus MATH data than between each MRI versus HSM data. All ICC values were >0.75 indicating that all four methods were reliable for measuring BD and that the mathematical algorithm and the two complimentary non-invasive MRI protocols could objectively and reliably estimate different types of breast tissues.

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

    Science.gov (United States)

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

    2016-11-01

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

  15. The contribution of different adipose tissue depots to plasma plasminogen activator inhibitor-1 (PAI-1) levels.

    Science.gov (United States)

    Barnard, Sunelle A; Pieters, Marlien; De Lange, Zelda

    2016-11-01

    Increased plasma plasminogen activator inhibitor-1 (PAI-1) level is considered a mechanistic pathway through which obesity contributes to increased cardiovascular disease risk. Abdominal adipose tissue specifically, is a major PAI-1 source with visceral adipose tissue (VAT), an ectopic fat depot, generally considered to produce more PAI-1 than subcutaneous adipose tissue. However, this does not necessarily lead to increased plasma PAI-1 levels. This review provides an overview of studies investigating the association between body fat distribution and plasma PAI-1 levels. It discusses factors that influence this relationship and also considers the contribution of other tissue to plasma PAI-1 levels, placing the relative contribution of adipose tissue into perspective. In conclusion, the relationship between VAT and plasma PAI-1 levels is not fixed but can be modulated by a number of factors such as the size of the subcutaneous adipose tissue depot, ethnicity, possibly genetics and other obesity-related metabolic abnormalities.

  16. A Nonpalpable Nodule in Ectopic Axillary Breast Tissue: Consider Phyllodes Tumor

    Science.gov (United States)

    Bautista-Piña, Verónica; Ramírez-Bollas, Julio; Espejo-Fonseca, Ruby; Rodríguez-Cuevas, Sergio

    2016-01-01

    Benign and malignant pathology can develop in ectopic axillary breast tissue, such as fibroadenomas, phyllodes tumors, and breast cancer. We present a rare case of an asymptomatic 43-year-old woman with an axillary nodule which was identified during screening mammography within ectopic axillary breast tissue, initially considered as a suspicious lymph node. Radiologic studies were considered as Breast Imaging-Reporting Data System (BI-RADS) 4. A hyperdense, lobular, and well-circumscribed nodule was identified in mammogram while the nodule by ultrasound (US) was hypoechoic with indistinct microlobular margins, without vascularity by Doppler, and measuring 1.26 × 1 cm. Core-needle biopsy reported a fibroepithelial neoplasm. The patient was submitted to local wide-needle excision located in intraoperative radiography of the surgical specimen and margin evaluation. Final histopathological study reported a 1.8 × 1.2 cm benign phyllodes tumor, with irregular, pushing, and clear wide margins within normal ectopic breast tissue. The patient without surgical complications continued annual screening without recurrence during a follow-up that took place 24 months later. PMID:28105378

  17. Low-temperature plasma needle effects on cultured metastatic breast cancer cells

    Science.gov (United States)

    Knecht, Sean; Bilen, Sven; Micci, Michael; Brubaker, Timothy; Wilson, Michael; Cook, Ian; Czesak, Nicholas; Hipkins, Garret

    2015-11-01

    The Penn State Low-Temperature Plasma group is presently investigating the applications of low-temperature plasma for biomedical applications, including the effects on MDA-MB-231 metastatic breast cancer cells. A plasma needle system has been designed and constructed that consists of a 22-gauge stainless steel syringe needle, which acts as the high-voltage electrode, covered with PEEK tubing as the dielectric with a ring ground electrode on the outside. The system is driven by a low-frequency AC voltage amplifier, with typical operating conditions of 2-5 kV peak voltage at 5 kHz. Helium is used as the working fluid and produces a plasma jet with ~ cm's visible extent. Cultured breast cancer cells were provided by our collaborator and exposed to the plasma needle for varying doses and detachment of cells was observed. The effects are attributed to reactive oxygen and nitrogen species generation and transport through the cell culture medium. Plasma needle characterization and the results of the breast cancer experiments will be presented.

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

    Science.gov (United States)

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

    1999-05-01

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

  19. Methylation profiling of 48 candidate genes in tumor and matched normal tissues from breast cancer patients.

    Science.gov (United States)

    Li, Zibo; Guo, Xinwu; Wu, Yepeng; Li, Shengyun; Yan, Jinhua; Peng, Limin; Xiao, Zhi; Wang, Shouman; Deng, Zhongping; Dai, Lizhong; Yi, Wenjun; Xia, Kun; Tang, Lili; Wang, Jun

    2015-02-01

    Gene-specific methylation alterations in breast cancer have been suggested to occur early in tumorigenesis and have the potential to be used for early detection and prevention. The continuous increase in worldwide breast cancer incidences emphasizes the urgent need for identification of methylation biomarkers for early cancer detection and patient stratification. Using microfluidic PCR-based target enrichment and next-generation bisulfite sequencing technology, we analyzed methylation status of 48 candidate genes in paired tumor and normal tissues from 180 Chinese breast cancer patients. Analysis of the sequencing results showed 37 genes differentially methylated between tumor and matched normal tissues. Breast cancer samples with different clinicopathologic characteristics demonstrated distinct profiles of gene methylation. The methylation levels were significantly different between breast cancer subtypes, with basal-like and luminal B tumors having the lowest and the highest methylation levels, respectively. Six genes (ACADL, ADAMTSL1, CAV1, NPY, PTGS2, and RUNX3) showed significant differential methylation among the 4 breast cancer subtypes and also between the ER +/ER- tumors. Using unsupervised hierarchical clustering analysis, we identified a panel of 13 hypermethylated genes as candidate biomarkers that performed a high level of efficiency for cancer prediction. These 13 genes included CST6, DBC1, EGFR, GREM1, GSTP1, IGFBP3, PDGFRB, PPM1E, SFRP1, SFRP2, SOX17, TNFRSF10D, and WRN. Our results provide evidence that well-defined DNA methylation profiles enable breast cancer prediction and patient stratification. The novel gene panel might be a valuable biomarker for early detection of breast cancer.

  20. Polarized spectral features of human breast tissues through wavelet transform and principal component analysis

    Indian Academy of Sciences (India)

    Anita Gharekhan; Ashok N Oza; M B Sureshkumar; Asima Pradhan; Prasanta K Panigrahi

    2010-12-01

    Fluorescence characteristics of human breast tissues are investigated through wavelet transform and principal component analysis (PCA). Wavelet transform of polarized fluorescence spectra of human breast tissues is found to localize spectral features that can reliably differentiate different tissue types. The emission range in the visible wavelength regime of 500–700 nm is analysed, with the excitation wavelength at 488 nm using laser as an excitation source, where flavin and porphyrin are some of the active fluorophores. A number of global and local parameters from principal component analysis of both high- and low-pass coefficients extracted in the wavelet domain, capturing spectral variations and subtle changes in the diseased tissues are clearly identifiable.

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

    Directory of Open Access Journals (Sweden)

    James Ryan

    Full Text Available INTRODUCTION: The presence, relevance and regulation of the Sodium Iodide Symporter (NIS in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro. METHODS: Human breast tissue specimens (malignant n = 75, normal n = 15, fibroadenoma n = 10 were analysed by RQ-PCR targeting NIS, receptors for retinoic acid (RARα, RARβ, oestrogen (ERα, thyroid hormones (THRα, THRβ, and also phosphoinositide-3-kinase (PI3K. Breast cancer cells were treated with Retinoic acid (ATRA, Estradiol and Thyroxine individually and in combination followed by analysis of changes in NIS expression. RESULTS: The lowest levels of NIS were detected in normal tissue (Mean(SEM 0.70(0.12 Log(10 Relative Quantity (RQ with significantly higher levels observed in fibroadenoma (1.69(0.21 Log(10RQ, p<0.005 and malignant breast tissue (1.18(0.07 Log(10RQ, p<0.05. Significant positive correlations were observed between human NIS and ERα (r = 0.22, p<0.05 and RARα (r = 0.29, p<0.005, with the strongest relationship observed between NIS and RARβ (r = 0.38, p<0.0001. An inverse relationship between NIS and PI3K expression was also observed (r =  0.21, p<0.05. In vitro, ATRA, Estradiol and Thyroxine individually stimulated significant increases in NIS expression (range 6-16 fold, while ATRA and Thyroxine combined caused the greatest increase (range 16-26 fold. CONCLUSION: Although NIS expression is significantly higher in malignant compared to normal breast tissue, the highest level was detected in fibroadenoma. The data presented supports a role for retinoic acid and estradiol in mammary NIS regulation in vivo, and also highlights potential thyroidal regulation of mammary NIS mediated by thyroid hormones.

  2. Protein profile study of breast cancer tissues using HPLC-LIF: a pilot study

    Science.gov (United States)

    Menon, Suraj; Sujatha; Kumar, K. Kalyan; Kurien, Jacob; Krishnanand, B. R.; Mahato, K. K.; George, Sajan D.; Kartha, V. B.; C, Santhosh

    2007-02-01

    Proteomics based techniques are rapidly emerging as alternative techniques to conventional histo-pathological methods for detection and diagnosis of cancers. Tumor markers are of considerable importance in the study of various cancers. A study of various changes in the protein profile associated with breast cancer will facilitate a better understanding of the various dynamic changes associated with the disease. In our study we have used High Performance Liquid Chromatography coupled with highly sensitive Laser Induced Fluorescence for recording the protein profiles of breast tissue homogenates. The protein profiles were recorded from pathologically certified normal as well as malignant breast tissue samples. The recorded protein profiles were studied by using Principal Component Analysis. Good discrimination of normal, benign and malignant samples was achieved in this pilot study.

  3. Plasma HER2 amplification in cell-free DNA during neoadjuvant chemotherapy in breast cancer

    DEFF Research Database (Denmark)

    Bechmann, Troels; Andersen, Rikke Fredslund; Pallisgaard, Niels

    2013-01-01

    Measurement of human epidermal growth factor receptor 2 (HER2) gene amplification in cell-free DNA (cfDNA) is an evolving technique in breast cancer, enabling liquid biopsies and treatment monitoring. The present study investigated the dynamics of plasma HER2 gene copy number and amplification in...... in cfDNA during neoadjuvant chemotherapy....

  4. Optical study on the dependence of breast tissue composition and structure on subject anamnesis

    Science.gov (United States)

    Taroni, Paola; Quarto, Giovanna; Pifferi, Antonio; Abbate, Francesca; Balestreri, Nicola; Menna, Simona; Cassano, Enrico; Cubeddu, Rinaldo

    2015-07-01

    Time domain multi-wavelength (635 to 1060 nm) optical mammography was performed on 200 subjects to estimate their average breast tissue composition in terms of oxy- and deoxy-hemoglobin, water, lipid and collagen, and structural information, as provided by scattering parameters (amplitude and power). Significant (and often marked) dependence of tissue composition and structure on age, menopausal status, body mass index, and use of oral contraceptives was demonstrated.

  5. Growth of human breast tissues from patient cells in 3D hydrogel scaffolds.

    Science.gov (United States)

    Sokol, Ethan S; Miller, Daniel H; Breggia, Anne; Spencer, Kevin C; Arendt, Lisa M; Gupta, Piyush B

    2016-03-01

    Three-dimensional (3D) cultures have proven invaluable for expanding human tissues for basic research and clinical applications. In both contexts, 3D cultures are most useful when they (1) support the outgrowth of tissues from primary human cells that have not been immortalized through extensive culture or viral infection and (2) include defined, physiologically relevant components. Here we describe a 3D culture system with both of these properties that stimulates the outgrowth of morphologically complex and hormone-responsive mammary tissues from primary human breast epithelial cells. Primary human breast epithelial cells isolated from patient reduction mammoplasty tissues were seeded into 3D hydrogels. The hydrogel scaffolds were composed of extracellular proteins and carbohydrates present in human breast tissue and were cultured in serum-free medium containing only defined components. The physical properties of these hydrogels were determined using atomic force microscopy. Tissue growth was monitored over time using bright-field and fluorescence microscopy, and maturation was assessed using morphological metrics and by immunostaining for markers of stem cells and differentiated cell types. The hydrogel tissues were also studied by fabricating physical models from confocal images using a 3D printer. When seeded into these 3D hydrogels, primary human breast epithelial cells rapidly self-organized in the absence of stromal cells and within 2 weeks expanded to form mature mammary tissues. The mature tissues contained luminal, basal, and stem cells in the correct topological orientation and also exhibited the complex ductal and lobular morphologies observed in the human breast. The expanded tissues became hollow when treated with estrogen and progesterone, and with the further addition of prolactin produced lipid droplets, indicating that they were responding to hormones. Ductal branching was initiated by clusters of cells expressing putative mammary stem cell

  6. Tissue microarray analysis as a screening tool for neuroendocrine carcinoma of the breast

    DEFF Research Database (Denmark)

    Brask, Julie Benedicte; Talman, Maj-Lis Møller; Wielenga, Vera Timmermans

    2014-01-01

    by investigating the usefulness of tissue microarray (TMA) analysis as a screening tool. We present our findings with regard to sensitivity and specificity compared with whole-mount sections. The material consists of 240 cases of breast cancer divided into 20 TMA blocks that were all immunohistochemically stained...

  7. [Plasma and tissue lipids in rats after a flight on the Kosmos-936 biosatellite].

    Science.gov (United States)

    Ahlers, J; Tigranian, R A; Praslická, M

    1982-01-01

    The content of triglycerides, total cholesterol, phospholipids and nonesterified fatty acids was measured in plasma and tissues of rats flown for 18.5 days on Cosmos-936 in the weightless and centrifuged state. The weightlessness exposure increased lipid fractions in plasma and tissues, and artificial gravity produced a beneficial effect.

  8. Differential profiling of breast cancer plasma proteome by isotope-coded affinity tagging method reveals biotinidase as a breast cancer biomarker

    Directory of Open Access Journals (Sweden)

    Yu Myeong-Hee

    2010-03-01

    Full Text Available Abstract Background Breast cancer is one of the leading causes of women's death worldwide. It is important to discover a reliable biomarker for the detection of breast cancer. Plasma is the most ideal source for cancer biomarker discovery since many cells cross-communicate through the secretion of soluble proteins into blood. Methods Plasma proteomes obtained from 6 breast cancer patients and 6 normal healthy women were analyzed by using the isotope-coded affinity tag (ICAT labeling approach and tandem mass spectrometry. All the plasma samples used were depleted of highly abundant 6 plasma proteins by immune-affinity column chromatography before ICAT labeling. Several proteins showing differential abundance level were selected based on literature searches and their specificity to the commercially available antibodies, and then verified by immunoblot assays. Results A total of 155 proteins were identified and quantified by ICAT method. Among them, 33 proteins showed abundance changes by more than 1.5-fold between the plasmas of breast cancer patients and healthy women. We chose 5 proteins for the follow-up confirmation in the individual plasma samples using immunoblot assay. Four proteins, α1-acid glycoprotein 2, monocyte differentiation antigen CD14, biotinidase (BTD, and glutathione peroxidase 3, showed similar abundance ratio to ICAT result. Using a blind set of plasmas obtained from 21 breast cancer patients and 21 normal healthy controls, we confirmed that BTD was significantly down-regulated in breast cancer plasma (Wilcoxon rank-sum test, p = 0.002. BTD levels were lowered in all cancer grades (I-IV except cancer grade zero. The area under the receiver operating characteristic curve of BTD was 0.78. Estrogen receptor status (p = 0.940 and progesterone receptor status (p = 0.440 were not associated with the plasma BTD levels. Conclusions Our study suggests that BTD is a potential serological biomarker for the detection of breast cancer.

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

    Science.gov (United States)

    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.

  10. Effects of DC bias voltages on the RF-excited plasma-tissue interaction

    Science.gov (United States)

    Yang, Aijun; Liu, Dingxin; Wang, Xiaohua; Li, Jiafeng; Chen, Chen; Rong, Mingzhe; Kong, Michael G.

    2016-10-01

    We present in this study how DC bias voltage impacts on the fluxes of reactive species on the skin tissue by means of a plasma-tissue interaction model. The DC bias voltage inputs less than 2% of the total discharge power, and hence it has little influence on the whole plasma characteritics including the volume-averaged densities of reactive species and the heating effect. However, it pushes the plasma bulk towards the skin surface, which significantly changes the local plasma characteristics in the vicinity of the skin surface, and in consequence remarkably enhances the flux densities of reactive species on the skin tissue. With the consideration of plasma dosage and heat damage on the skin tissue, DC bias voltage is a better approach compared with the common approach of increasing the plasma power. Since the DC voltage is easy to apply on the human body, it is a promising approach for use in clincial applications.

  11. X-ray scattering for the characterization of lyophilized breast tissue samples

    Science.gov (United States)

    Elshemey, Wael M.; Mohamed, Fayrouz S.; Khater, Ibrahim M.

    2013-09-01

    This work investigates the possibility of characterizing breast cancer by measuring the X-ray scattering profiles of lyophilized excised breast tissue samples. Since X-ray scattering from water-rich tissue is dominated by scattering from water, the removal of water by lyophilization would enhance the characterization process. In the present study, X-ray scattering profiles of 22 normal, 22 malignant and 10 benign breast tissue samples are measured. The cut-offs of scatter diagrams, sensitivity, specificity and diagnostic accuracy of three characterization parameters (full width at half maximum (FWHM) for the peak at 1.1 nm-1, area under curve (AUC), and ratio of 1st to 2nd scattering peak intensities (I1/I2%)) are calculated and compared to the data from non-lyophilized samples. Results show increased sensitivity (up to 100%) of the present data on lyophilized breast tissue samples compared to previously reported data for non-lyophilized samples while the specificity (up to 95.4%), diagnostic accuracy (up to 95.4%) and receiver operating characteristic (ROC) curve values (up to 0.9979) for both sets of data are comparable. The present study shows significant differences between normal samples and each of malignant and benign samples. Only subtle differences exist between malignant and benign lyophilized breast tissue samples where FWHM=0.7±0.1 and 0.8±0.3, AUC=1.3±0.2 and 1.4±0.2 and I1/I2%=44.9±11.0 and 52.4±7.6 for malignant and benign samples respectively.

  12. Automated adipose study for assessing cancerous human breast tissue using optical coherence tomography (Conference Presentation)

    Science.gov (United States)

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

    2017-02-01

    Breast cancer is the third leading cause of death in women in the United States. In human breast tissue, adipose cells are infiltrated or replaced by cancer cells during the development of breast tumor. Therefore, an adipose map can be an indicator of identifying cancerous region. We developed an automated classification method to generate adipose map within human breast. To facilitate the automated classification, we first mask the B-scans from OCT volumes by comparing the signal noise ratio with a threshold. Then, the image was divided into multiple blocks with a size of 30 pixels by 30 pixels. In each block, we extracted texture features such as local standard deviation, entropy, homogeneity, and coarseness. The features of each block were input to a probabilistic model, relevance vector machine (RVM), which was trained prior to the experiment, to classify tissue types. For each block within the B-scan, RVM identified the region with adipose tissue. We calculated the adipose ratio as the number of blocks identified as adipose over the total number of blocks within the B-scan. We obtained OCT images from patients (n = 19) in Columbia medical center. We automatically generated the adipose maps from 24 B-scans including normal samples (n = 16) and cancerous samples (n = 8). We found the adipose regions show an isolated pattern that in cancerous tissue while a clustered pattern in normal tissue. Moreover, the adipose ratio (52.30 ± 29.42%) in normal tissue was higher than the that in cancerous tissue (12.41 ± 10.07%).

  13. Does Acellular Dermal Matrix Thickness Affect Complication Rate in Tissue Expander Based Breast Reconstruction?

    Directory of Open Access Journals (Sweden)

    Jessica F. Rose

    2016-01-01

    Full Text Available Background. While the benefits of using acellular dermal matrices (ADMs in breast reconstruction are well described, their use has been associated with additional complications. The purpose of this study was to determine if ADM thickness affects complications in breast reconstruction. Methods. A retrospective chart review was performed including all tissue expander based breast reconstructions with AlloDerm (LifeCell, Branchburg, NJ over 4 years. We evaluated preoperative characteristics and assessed postoperative complications including seroma, hematoma, infection, skin necrosis, and need for reintervention. We reviewed ADM thickness and time to Jackson-Pratt (JP drain removal. Results. Fifty-five patients underwent 77 ADM-associated tissue expander based breast reconstructions, with average age of 48.1 years and average BMI of 25.9. Average ADM thickness was 1.21 mm. We found higher complication rates in the thick ADM group. Significant associations were found between smokers and skin necrosis (p<0.0001 and seroma and prolonged JP drainage (p=0.0004; radiated reconstructed breasts were more likely to suffer infections (p=0.0085, and elevated BMI is a significant predictor for increased infection rate (p=0.0037. Conclusion. We found a trend toward increased complication rates with thicker ADMs. In the future, larger prospective studies evaluating thickness may provide more information.

  14. Diagnosis of breast cancer by polarization cartography of human blood plasma

    Science.gov (United States)

    Mintser, Ozar P.; Oliinychenko, B. P.

    2012-01-01

    The possibilities of polarization-optical diagnostics of plasma protein structures changes, which are connected with the breast pathologies, were investigated. As the main investigation object it has been used the coordinate structure of polarization states distributions of blood plasma images. The results were obtained by means of novel technique of digital polarimetry. The results of investigating the interrelation between the values of correlation (correlation area, asymmetry coefficient and autocorrelation function excess) and fractal (dispersion of logarithmic dependencies of power spectra) parameters are presented. They characterize the coordinate distributions of polarization azimuth of laser images of blood plasma smears and pathological state of the organism. The diagnostic criteria of breast cancer nascency are determined.

  15. Anti-thyroid peroxidase antibodies: Its effect on thyroid gland and breast tissue

    Directory of Open Access Journals (Sweden)

    Sabitha Kandi

    2012-01-01

    Full Text Available Thyroid peroxidase (TPO is a key enzyme in the synthesis of thyroid hormone. TPO is involved in thyroid hormone synthesis (organification and coupling reactions. TPO is a major antigen corresponding to thyroid-microsomal autoantibodies. Anti-TPO auto antibodies are very important to diagnose autoimmune thyroid diseases and also in estimating its clinical course. Autoimmune thyroid disease is detected mostly by measuring circulating antibodies to thyroglobulin which is uncommon measurement of antibodies to TPO that gives reliable information about autoimmune thyroid disease. Eighty percent of Grave′s disease patients have high levels of antiTPO antibodies. About 4% of subclinical hypothyroid patients with positive TPO antibodies develop clinical hypothyroidism. There is always a controversy on the relationship between breast cancer and thyroid disorders. As these tissues, i.e., breast and thyroid, originate embryologically from the same type of cells, hypothyroid/hyperthyroid females are more prone to develop benign or malignant breast tumors. The studies on breast cancer patients indicate increased thyroid disorders in breast cancer patients, most commonly Hashimoto′s thyroiditis accounts to increased thyroid disorders in these patients. This is independent of hormonal receptor status of the patient. These findings suggest the usefulness of screening for thyroid disease in any patient with breast cancer.

  16. Breast tissue classification using x-ray scattering measurements and multivariate data analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ryan, Elaine A; Farquharson, Michael J [School of Allied Health Sciences, City University, Charterhouse Square, London EC1M 6PA (United Kingdom)

    2007-11-21

    This study utilized two radiation scatter interactions in order to differentiate malignant from non-malignant breast tissue. These two interactions were Compton scatter, used to measure the electron density of the tissues, and coherent scatter to obtain a measure of structure. Measurements of these parameters were made using a laboratory experimental set-up comprising an x-ray tube and HPGe detector. The breast tissue samples investigated comprise five different tissue classifications: adipose, malignancy, fibroadenoma, normal fibrous tissue and tissue that had undergone fibrocystic change. The coherent scatter spectra were analysed using a peak fitting routine, and a technique involving multivariate analysis was used to combine the peak fitted scatter profile spectra and the electron density values into a tissue classification model. The number of variables used in the model was refined by finding the sensitivity and specificity of each model and concentrating on differentiating between two tissues at a time. The best model that was formulated had a sensitivity of 54% and a specificity of 100%.

  17. Breast tissue classification using x-ray scattering measurements and multivariate data analysis

    Science.gov (United States)

    Ryan, Elaine A.; Farquharson, Michael J.

    2007-11-01

    This study utilized two radiation scatter interactions in order to differentiate malignant from non-malignant breast tissue. These two interactions were Compton scatter, used to measure the electron density of the tissues, and coherent scatter to obtain a measure of structure. Measurements of these parameters were made using a laboratory experimental set-up comprising an x-ray tube and HPGe detector. The breast tissue samples investigated comprise five different tissue classifications: adipose, malignancy, fibroadenoma, normal fibrous tissue and tissue that had undergone fibrocystic change. The coherent scatter spectra were analysed using a peak fitting routine, and a technique involving multivariate analysis was used to combine the peak fitted scatter profile spectra and the electron density values into a tissue classification model. The number of variables used in the model was refined by finding the sensitivity and specificity of each model and concentrating on differentiating between two tissues at a time. The best model that was formulated had a sensitivity of 54% and a specificity of 100%.

  18. A polynomial hyperelastic model for the mixture of fat and glandular tissue in female breast.

    Science.gov (United States)

    Calvo-Gallego, Jose L; Martínez-Reina, Javier; Domínguez, Jaime

    2015-09-01

    In the breast of adult women, glandular and fat tissues are intermingled and cannot be clearly distinguished. This work studies if this mixture can be treated as a homogenized tissue. A mechanical model is proposed for the mixture of tissues as a function of the fat content. Different distributions of individual tissues and geometries have been tried to verify the validity of the mixture model. A multiscale modelling approach was applied in a finite element model of a representative volume element (RVE) of tissue, formed by randomly assigning fat or glandular elements to the mesh. Both types of tissues have been assumed as isotropic, quasi-incompressible hyperelastic materials, modelled with a polynomial strain energy function, like the homogenized model. The RVE was subjected to several load cases from which the constants of the polynomial function of the homogenized tissue were fitted in the least squares sense. The results confirm that the fat volume ratio is a key factor in determining the properties of the homogenized tissue, but the spatial distribution of fat is not so important. Finally, a simplified model of a breast was developed to check the validity of the homogenized model in a geometry similar to the actual one.

  19. Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues

    Directory of Open Access Journals (Sweden)

    Nardulli Ann M

    2010-01-01

    Full Text Available Abstract Background During the course of normal cellular metabolism, oxygen is consumed and reactive oxygen species (ROS are produced. If not effectively dissipated, ROS can accumulate and damage resident proteins, lipids, and DNA. Enzymes involved in redox regulation and DNA repair dissipate ROS and repair the resulting damage in order to preserve a functional cellular environment. Because increased ROS accumulation and/or unrepaired DNA damage can lead to initiation and progression of cancer and we had identified a number of oxidative stress and DNA repair proteins that influence estrogen responsiveness of MCF-7 breast cancer cells, it seemed possible that these proteins might be differentially expressed in normal mammary tissue, benign hyperplasia (BH, ductal carcinoma in situ (DCIS and invasive breast cancer (IBC. Methods Immunohistochemistry was used to examine the expression of a number of oxidative stress proteins, DNA repair proteins, and damage markers in 60 human mammary tissues which were classified as BH, DCIS or IBC. The relative mean intensity was determined for each tissue section and ANOVA was used to detect statistical differences in the relative expression of BH, DCIS and IBC compared to normal mammary tissue. Results We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue. Conclusions Our studies suggest that oxidative stress and DNA repair proteins not only protect normal cells from the damaging effects of ROS, but may also promote survival of mammary tumor cells.

  20. Effects of sample preparation on the optical properties of breast tissue

    Science.gov (United States)

    Marks, Fay A.

    1996-04-01

    The optical properties of biological tissue should be determined in vivo whenever possible. However, for those instances when in vivo studies are impractical, too expensive or inappropriate, and when blood flow is not an issue, the ability to perform in vitro studies then becomes invaluable. Optical absorption spectroscopy shows that it may be possible to obtain meaningful information about the optical properties of human breast tissue from in vitro samples if strict preparation and measuring protocols are used. That a strict protocol for storing and handling tissue is critical can be seen from our observations of changes in the optical absorption spectra that occur in response to formalin fixation, the passage of time, application of stains and dyes, and storage in growth medium of the excised tissue. In vivo optical absorption spectroscopy measurements have been made on human breast cancer xenografts and compared with in vitro measurements on breast biopsies prepared according to precise collection and treatment protocols. There is a 'window of opportunity' before time dependent changes in the UV optical absorption spectra of the excised tissue specimens occur. This time window of opportunity widens at longer wavelengths with the least changes occurring in the optical spectra in the NIR.

  1. Blind breast tissue diagnosis using independent component analysis of localized backscattering response

    Science.gov (United States)

    Eguizabal, Alma; Laughney, Ashley M.; García Allende, Pilar Beatriz; Krishnaswamy, Venkataramanan; Wells, Wendy A.; Paulsen, Keith D.; Pogue, Brian W.; Lopez-Higuera, Jose M.; Conde, Olga M.

    2012-03-01

    A blind separation technique based on Independent Component Analysis (ICA) is proposed for breast tumor delineation and pathologic diagnosis. Tissue morphology is determined by fitting local measures of tissue reflectance to a Mie theory approximation, parameterizing the scattering power, scattering amplitude and average scattering irradiance. ICA is applied on the scattering parameters by spatial analysis using the Fast ICA method to extract more determinant features for an accurate diagnostic. Neither training, nor comparisons with reference parameters are required. Tissue diagnosis is provided directly following ICA application to the scattering parameter images. Surgically resected breast tissues were imaged and identified by a pathologist. Three different tissue pathologies were identified in 29 samples and classified as not-malignant, malignant and adipose. Scatter plot analysis of both ICA results and optical parameters where obtained. ICA subtle ameliorates those cases where optical parameter's scatter plots were not linearly separable. Furthermore, observing the mixing matrix of the ICA, it can be decided when the optical parameters themselves are diagnostically powerful. Moreover, contrast maps provided by ICA correlate with the pathologic diagnosis. The time response of the diagnostic strategy is therefore enhanced comparing with complex classifiers, enabling near real-time assessment of pathology during breast-conserving surgery.

  2. Proteomic Analysis of Stage-II Breast Cancer from Formalin-Fixed Paraffin-Embedded Tissues

    Directory of Open Access Journals (Sweden)

    Naif Abdullah Al-Dhabi

    2016-01-01

    Full Text Available Breast cancer is the most frequently occurring disease among women worldwide. The early stage of breast cancer identification is the key challenge in cancer control and prevention procedures. Although gene expression profiling helps to understand the molecular mechanism of diseases or disorder in the living system, gene expression pattern alone is not sufficient to predict the exact mechanisms. Current proteomics tools hold great application for analysis of cancerous conditions. Hence, the generation of differential protein expression profiles has been optimized for breast cancer and normal tissue samples in our organization. Normal and tumor tissues were collected from 20 people from a local hospital. Proteins from the diseased and normal tissues have been investigated by 2D gel electrophoresis and MALDI-TOF-MS. The peptide mass fingerprint data were fed into various public domains like Mascot, MS-Fit, and Pept-ident against Swiss-Prot protein database and the proteins of interest were identified. Some of the differentially expressed proteins identified were human annexin, glutathione S-transferase, vimentin, enolase-1, dihydrolipoamide dehydrogenase, glutamate dehydrogenase, Cyclin A1, hormone sensitive lipase, beta catenin, and so forth. Many types of proteins were identified as fundamental steps for developing molecular markers for diagnosis of human breast cancer as well as making a new proteomic database for future research.

  3. Cancer Grafted in Aberrant Breast Tissue Cáncer injertado en tejido mamario aberrante

    Directory of Open Access Journals (Sweden)

    Lidia Torres Ajá

    2012-03-01

    Full Text Available Among the anomalies during embryonic development of the breasts we may find supernumerary breasts and aberrant ectopic tissue. In both of them, malignant tumors of the breast can proliferate, mostly in aberrant tissue. We present the case of a female patient aged 73, who refers to have always had a "little mammary gland in the left submammary that never caused discomfort to the last two months when its volume increased and the skin retracted". Excisional biopsy allowed diagnosing an infiltrating ductal carcinoma, the first case of carcinoma grafted in aberrant breast tissue diagnosed in the province.

    Entre las anomalías del desarrollo embrionario de las mamas se encuentran las mamas supernumerarias y el tejido ectópico aberrante. Ambas pueden ser asiento de tumores malignos de la mama, en mayor número  el tejido aberrante. Se presenta el caso de una paciente femenina de 73 años, que refiere tiene desde siempre una “mamita pequeña en el surco submamario izquierdo la cual nunca le ocasiono molestias hasta hace 2 meses en que aumentó de volumen y se le retrajo la piel". Mediante biopsia escisional se le diagnostica un carcinoma ductal infiltrante, siendo así  el primer caso de carcinoma injertado en tejido mamario aberrante diagnosticado en nuestra provincia.

  4. An Algorithmic Approach to Total Breast Reconstruction with Free Tissue Transfer

    Directory of Open Access Journals (Sweden)

    Seong Cheol Yu

    2013-05-01

    Full Text Available As microvascular techniques continue to improve, perforator flap free tissue transfer is now the gold standard for autologous breast reconstruction. Various options are available for breast reconstruction with autologous tissue. These include the free transverse rectus abdominis myocutaneous (TRAM flap, deep inferior epigastric perforator flap, superficial inferior epigastric artery flap, superior gluteal artery perforator flap, and transverse/vertical upper gracilis flap. In addition, pedicled flaps can be very successful in the right hands and the right patient, such as the pedicled TRAM flap, latissimus dorsi flap, and thoracodorsal artery perforator. Each flap comes with its own advantages and disadvantages related to tissue properties and donor-site morbidity. Currently, the problem is how to determine the most appropriate flap for a particular patient among those potential candidates. Based on a thorough review of the literature and accumulated experiences in the author’s institution, this article provides a logical approach to autologous breast reconstruction. The algorithms presented here can be helpful to customize breast reconstruction to individual patient needs.

  5. The contributions of the tissue inhibitor of metalloproteinase-1 genotypes to triple negative breast cancer risk.

    Science.gov (United States)

    Chang, Wen-Shin; Liu, Liang-Chih; Hsiao, Chieh-Lun; Su, Chen-Hsien; Wang, Hwei-Chung; Ji, Hong-Xue; Tsai, Chia-Wen; Maa, Ming-Chei; Bau, Da-Tian

    2016-03-01

    The tissue inhibitors of metalloproteinases (TIMPs) are a family of multifunctional proteins which have been shown to be upregulated in various types of cancers. However, the contribution of TIMPs in breast cancer is not fully understood, not to mention triple negative breast cancer (TNBC). This study's aim was to evaluate the contribution of TIMP-1 rs4898, rs6609533, and rs2070584 genotypes to the risk of breast cancer, especially the subtype of TNBC. The contributions of these TIMP-1 genotypes to cancer risk were examined among 1232 breast cancer patients and 1232 healthy controls, and several clinicopathologic factors were also analyzed. The results showed that the percentages of CC, CT, and TT of TIMP-1 rs4898 were differentially distributed at 28.5%, 33.1% and 38.4% in the breast cancer patient group and 34.5%, 41.0% and 24.5% in the control group, respectively (P for trend = 7.99*10(-13)). It was also found that the CC genotype carriers were of increased risk for breast cancer (odds ratio = 1.90, 95% confidence interval = 1.55-2.33, P = 0.0001) than the TT genotype carriers. In addition, we analyzed the allelic frequency distributions of all three TIMP-1s, and the results showed that the C allele of TIMP-1 rs4898 contributes to an increase in breast cancer susceptibility (P = 2.41*10(-12)). On the other hand, there was no difference found in the distribution of genotypic or allelic frequencies among the patients and the controls for TIMP-1 rs6609533 and rs2070584. Thus, it is our conclusion that the CC genotype of TIMP-1 rs4898 compared to the TT wild-type genotype may increase the risk for breast cancer, especially TNBC in Taiwan, and may serve as an early detective and predictive marker.

  6. Association of tissue inhibitor of metalloproteinases-1 and Ki67 in estrogen receptor positive breast cancer

    DEFF Research Database (Denmark)

    Bjerre, Christina Annette; Knoop, Ann; Bjerre, Karsten;

    2013-01-01

    Background. The role of tissue inhibitor of metalloproteinases-1 (TIMP-1) in estrogen receptor (ER) positive breast cancer remains to be fully elucidated. We evaluated TIMP-1 as a prognostic marker in patients treated with adjuvant tamoxifen and investigated TIMP-1s association with Ki67 and ER...... = 0.48; OR 0.68; 95% CI 0.23-1.99). Conclusion. TIMP-1 does not appear to be prognostic in breast cancer patients receiving adjuvant tamoxifen. We identified a negative association between TIMP-1 and Ki67. We did not confirm our previous in vitro findings of a negative association between TIMP-1...

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

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    Liu Suling

    2008-07-01

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

  8. Magnetic resonance imaging (MRI) evaluation of residual breast tissue following mastectomy and reconstruction with silicone implants.

    Science.gov (United States)

    Zippel, Douglas; Tsehmaister-Abitbol, Vered; Rundstein, Arie; Shalmon, Anat; Zbar, Andrew; Nardini, Gil; Novikov, Ilya; Sklair-Levy, Miri

    2015-01-01

    We present our use of magnetic resonance (MR) measurement to determine the amount of residual breast tissue (RBT) following total mastectomy with reconstruction. Breast MR images of 45 women who underwent surgery between January and November 2011 were reviewed. The cohort included therapeutic and prophylactic mastectomies. RBT was evaluated at four points with a digital caliper assessing T2-weighted and T1-weighted images. Patients undergoing mastectomy for carcinoma tended to have less RBT than in prophylactic surgery. Greater age and recent surgery both correlated with larger RBT. Variable thickness of RBT is demonstrable following mastectomy and implant reconstruction using MR imaging. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Association between plasma metabolites and gene expression profiles in five porcine endocrine tissues

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    Bassols Anna

    2011-07-01

    Full Text Available Abstract Background Endocrine tissues play a fundamental role in maintaining homeostasis of plasma metabolites such as non-esterified fatty acids and glucose, the levels of which reflect the energy balance or the health status of animals. However, the relationship between the transcriptome of endocrine tissues and plasma metabolites has been poorly studied. Methods We determined the blood levels of 12 plasma metabolites in 27 pigs belonging to five breeds, each breed consisting of both females and males. The transcriptome of five endocrine tissues i.e. hypothalamus, adenohypophysis, thyroid gland, gonads and backfat tissues from 16 out of the 27 pigs was also determined. Sex and breed effects on the 12 plasma metabolites were investigated and associations between genes expressed in the five endocrine tissues and the 12 plasma metabolites measured were analyzed. A probeset was defined as a quantitative trait transcript (QTT when its association with a particular metabolic trait achieved a nominal P value Results A larger than expected number of QTT was found for non-esterified fatty acids and alanine aminotransferase in at least two tissues. The associations were highly tissue-specific. The QTT within the tissues were divided into co-expression network modules enriched for genes in Kyoto Encyclopedia of Genes and Genomes or gene ontology categories that are related to the physiological functions of the corresponding tissues. We also explored a multi-tissue co-expression network using QTT for non-esterified fatty acids from the five tissues and found that a module, enriched in hypothalamus QTT, was positioned at the centre of the entire multi-tissue network. Conclusions These results emphasize the relationships between endocrine tissues and plasma metabolites in terms of gene expression. Highly tissue-specific association patterns suggest that candidate genes or gene pathways should be investigated in the context of specific tissues.

  10. Percutaneous irreversible electroporation for breast tissue and breast cancer: safety, feasibility, skin effects and radiologic-pathologic correlation in an animal study.

    Science.gov (United States)

    Li, Sheng; Chen, Fei; Shen, Lujun; Zeng, Qi; Wu, Peihong

    2016-08-05

    To study the safety, feasibility and skin effects of irreversible electroporation (IRE) for breast tissue and breast cancer in animal models. Eight pigs were used in this study. IRE was performed on the left breasts of the pigs with different skin-electrode distances, and the right breasts were used as controls. The electrodes were placed 1-8 mm away from the skin, with an electrode spacing of 1.5-2 cm. Imaging and pathological examinations were performed at specific time points for follow-up evaluation. Vital signs, skin damage, breast tissue changes and ablation efficacy were also closely observed. Eight rabbit models with or without VX2 breast tumor implantations were used to further assess the damage caused by and the repair of thin skin after IRE treatment for breast cancer. Contrast-enhanced ultrasound and elastosonography were used to investigate ablation efficacy and safety. During IRE, the color of the pig breast skin reversibly changed. When the skin-electrode distance was 3 mm, the breast skin clearly changed, becoming white in the center and purple in the surrounding region during IRE. One small purulent skin lesion was detected several days after IRE. When the skin-electrode distance was 5-8 mm, the breast skin became red during IRE. However, the skin architecture was normal when evaluated using gross pathology and hematoxylin-eosin staining. When the skin-electrode distance was 1 mm, skin atrophy and yellow glabrescence occurred in the rabbit breasts after IRE. When the skin-electrode distance was ≥5 mm, there was no skin damage in the rabbit model regardless of breast cancer implantation. After IRE, complete ablation of the targeted breast tissue or cancer was confirmed, and apoptosis was detected in the target tissue and outermost epidermal layer. In the ablated breasts of the surviving animals, complete mammary regeneration with normal skin and hair was observed. Furthermore, no massive fibrosis or mass formation were detected on

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

    Science.gov (United States)

    Ryan, James; Curran, Catherine E; Hennessy, Emer; Newell, John; Morris, John C; Kerin, Michael J; Dwyer, Roisin M

    2011-01-19

    The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro. Human breast tissue specimens (malignant n = 75, normal n = 15, fibroadenoma n = 10) were analysed by RQ-PCR targeting NIS, receptors for retinoic acid (RARα, RARβ), oestrogen (ERα), thyroid hormones (THRα, THRβ), and also phosphoinositide-3-kinase (PI3K). Breast cancer cells were treated with Retinoic acid (ATRA), Estradiol and Thyroxine individually and in combination followed by analysis of changes in NIS expression. The lowest levels of NIS were detected in normal tissue (Mean(SEM) 0.70(0.12) Log(10) Relative Quantity (RQ)) with significantly higher levels observed in fibroadenoma (1.69(0.21) Log(10)RQ, phuman NIS and ERα (r = 0.22, pfibroadenoma. The data presented supports a role for retinoic acid and estradiol in mammary NIS regulation in vivo, and also highlights potential thyroidal regulation of mammary NIS mediated by thyroid hormones.

  12. [A computerized manual for assessing the dosage absorbed by breast tissue in mammography].

    Science.gov (United States)

    Bagni, B; Pedrazzini, L

    1988-11-01

    The computerized translation of "Handbook of glandular tissue doses in mammography" (HHS publication FDA 85-8239) is presented. It is registered on floppy disk and suitable for use in MS-DOS on IBM personal computer, Olivetti or compatible. The manual collects data published by many authors and suggests a method to estimate the dose released to the glandular tissue (considered at risk for breast cancer) in the most commonly used conditions for mammography. Besides translation manual, the program holds an algorithm developed by the authors, which allows the dose to the glandular tissue to be evaluated, given the following data: projection: craniocaudal or mediolateral; compression level: firm or moderate; breast size: small, medium or large; breast composition: percentage of glandular tissue content (by weight); X-ray beam quality: HVL mm Al. The algorithm is obtained from a bidimensional fit of the original data and is based on the terms contained in the manual. The program flow is guided by menus that make the procedure suitable for inexperienced operators too, both for consulting and printing and for computing program.

  13. Overexpression of Gli1 in cancer interstitial tissues predicts early relapse after radical operation of breast cancer

    Institute of Scientific and Technical Information of China (English)

    Ying-Hua Li; Hai-Feng Gao; Yan Wang; Fang Liu; Xiao-Feng Tian; Yang Zhang

    2012-01-01

    Objective:To investigate whether Gli1 expression is important in relapse after radical operation of breast cancer.Methods:Using immunohistochemistry,Glil expression was analyzed in human primary breast cancer (n=284) and paracancerous tissues (n=20),and also in local lymph nodes (n=28) and metastatic lymph nodes (n=28).Results:Initial analysis of Gli1 expression in a small cohort of 20 breast tumors and their paracancerous tissues showed a tendency towards Gli1 overexpression in breast cancer tissues (P<0.001).Further,Gli1 expression in 284 breast cancer tissue samples was analyzed and a significant correlation was found between increased expression of nuclear Gli1 and unfavorable recurrence-free survival (RFS) (P<0.05).The nuclear expression of Gli1 in metastatic lymph nodes following relapse after radical operation was much higher than that in the local lymph nodes of primary carcinoma (P<0.05).Most interestingly,the expression of Gli1 was much higher in the interstitial tissues of the relapsed group than of the non-relapsed group (P<0.001).Conclusions:Breast cancer shows a high prevalence of Gli1 expression,which is significantly correlated with aggressive features and unfavorable RFS.Nuclear Gli1 overexpression,especially in the interstitial tissues,signified early relapse after radical operation of breast cancer.

  14. Upregulation of RHOXF2 and ODF4 Expression in Breast Cancer Tissues

    Directory of Open Access Journals (Sweden)

    Golnesa Kazemi-Oula

    2015-10-01

    Full Text Available Objective: During the past decade, the importance of biomarker discovery has been highlighted in many aspects of cancer research. Biomarkers may have a role in early detection of cancer, prognosis and survival evaluation as well as drug response. Cancer-testis antigens (CTAs have gained attention as cancer biomarkers because of their expression in a wide variety of tumors and restricted expression in testis. The aim of this study was to find putative biomarkers for breast cancer. Materials and Methods: In this applied-descriptive study, the expression of 4 CTAs, namely acrosin binding protein (ACRBP, outer dense fiber 4 (ODF4, Rhox homeobox family member 2 (RHOXF2 and spermatogenesis associated 19 (SPATA19 were analyzed at the transcript level in two breast cancer lines (MCF-7 and MDA-MB-231, 40 invasive ductal carcinoma samples and their adjacent normal tissues as well as 10 fibroadenoma samples by means of quantitative real-time reverse transcription polymerase chain reaction (RT-PCR. Results: All four genes were expressed in both cell lines. Expression of ODF4 and RHOXF2 was detected in 62.5% and 60% of breast cancer tissues but in 22.5 and 17.5% of normal tissues examined respectively. The expression of both RHOXF2 and ODF4 was upregulated in cancerous tissues compared with their normal adjacent tissues by 3.31- and 2.96-fold respectively. The expression of both genes was correlated with HER2/neu overexpression. RHOXF2 expression but not ODF4 was correlated with higher stages of tumors. However, no significant association was seen between expression patterns and estrogen and progesterone receptors status. Conclusion: ODF4 and RHOXF2 are proposed as putative breast cancer biomarkers at the transcript level. However, their expression at protein level should be evaluated in future studies.

  15. Complete tissue expander coverage by musculo-fascial flaps in immediate breast mound reconstruction after mastectomy.

    Science.gov (United States)

    Alani, Harith A; Balalaa, Nahed

    2013-10-01

    Immediate breast reconstruction with tissue expander has become an increasingly popular procedure. Complete coverage of the expander by a musculofascial layer provides an additional well-vascularised layer, reducing the rate of possible complications of skin necrosis, prosthesis displacement, and the late capsular contracture. Complete expander coverage can be achieved by a combination of pectoralis major muscle and adjacent thoracic fascia in selected patients. Seventy-five breast mounds in 59 patients were reconstructed, in the first stage a temporary tissue expander inserted immediately after mastectomy and a musculofascial layer composed of the pectoralis major muscle, the serratus anterior fascia, and the superficial pectoral fascia were created to cover the expander. The first stage was followed months later by implant insertion. Minor and major complications were reported in a period of follow-up ranging from 24-42 months (mean 31 months). Complete musculofascial coverage of the tissue expander was a simple and easy to learn technique providing that the patient has a well-formed and intact superficial pectoral and serratus anterior fascia. From a total of 75 breast mounds reconstructed, major complications rate was 4% (overall rate of 19.8%), including major seroma (n = 4), haematoma (n = 1), partial skin loss (n = 3), wound dehiscence (n = 1), major infection (n = 2), severe capsule contracture (n = 1), and expander displacement (n = 3). The serratus anterior fascia and the superficial pectoral fascia flaps can be effectively used as an autologous tissue layer to cover the lower and the lateral aspect of tissue expanders in immediate breast reconstruction after mastectomy.

  16. Breast Cancer and Estrogen Biosynthesis in Adipose Tissue

    Science.gov (United States)

    1998-10-01

    displaced inconspicuous nuclei (Fig. 1). Fibroblasts, on the other hand, are spindly cells with eosinophilic cytoplasms and dark and elongated nuclei...pre-ovulatory stage. During this stage, increasing stimulation of cAMP by FSH elevates expression of CYP19, CYP11A (P450scc) and LH receptor in granu ...aromatase expression occurs in a number of human tissues and cell types, including the syncytiotrophoblast of the placenta (13), ovarian granu - losa

  17. Large-scale proteomic identification of S100 proteins in breast cancer tissues

    Directory of Open Access Journals (Sweden)

    Cancemi Patrizia

    2010-09-01

    Full Text Available Abstract Background Attempts to reduce morbidity and mortality in breast cancer is based on efforts to identify novel biomarkers to support prognosis and therapeutic choices. The present study has focussed on S100 proteins as a potentially promising group of markers in cancer development and progression. One reason of interest in this family of proteins is because the majority of the S100 genes are clustered on a region of human chromosome 1q21 that is prone to genomic rearrangements. Moreover, there is increasing evidence that S100 proteins are often up-regulated in many cancers, including breast, and this is frequently associated with tumour progression. Methods Samples of breast cancer tissues were obtained during surgical intervention, according to the bioethical recommendations, and cryo-preserved until used. Tissue extracts were submitted to proteomic preparations for 2D-IPG. Protein identification was performed by N-terminal sequencing and/or peptide mass finger printing. Results The majority of the detected S100 proteins were absent, or present at very low levels, in the non-tumoral tissues adjacent to the primary tumor. This finding strengthens the role of S100 proteins as putative biomarkers. The proteomic screening of 100 cryo-preserved breast cancer tissues showed that some proteins were ubiquitously expressed in almost all patients while others appeared more sporadic. Most, if not all, of the detected S100 members appeared reciprocally correlated. Finally, from the perspective of biomarkers establishment, a promising finding was the observation that patients which developed distant metastases after a three year follow-up showed a general tendency of higher S100 protein expression, compared to the disease-free group. Conclusions This article reports for the first time the comparative proteomic screening of several S100 protein members among a large group of breast cancer patients. The results obtained strongly support the hypothesis

  18. Adipose tissue extracts plasma ammonia after sprint exercise in women and men

    DEFF Research Database (Denmark)

    Esbjörnsson, Mona; Bülow, Jens; Norman, Barbara;

    2006-01-01

    This study evaluates a possible contribution of adipose tissue to the elimination of plasma ammonia (NH(3)) after high-intensity sprint exercise. In 14 healthy men and women, repeated blood samples for plasma NH(3) analyses were obtained from brachial artery and from a subcutaneous abdominal vein...... before and after three repeated 30-s cycle sprints separated by 20 min of recovery. Biopsies from subcutaneous abdominal adipose tissue were obtained and analyzed for glutamine and glutamate content. After exercise, both arterial and abdominal venous plasma NH(3) concentrations were lower in women than...... in men (P adipose tissue. However, the fractional extraction (a...

  19. Diagnostic accuracy of real-time tissue elastography for breast cancer:a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Cong Wang; Guang Yang; Hui Wang

    2016-01-01

    Objective The present study aimed to determine the accuracy of real-time tissue elastography (RTE) for the diagnosis of breast cancer. Methods The search was conducted in the PubMed, Web of Science, Cochrane Library, and China Biology Medicine databases from inception through December 31, 2014, without language restrictions. The meta-analysis was conducted using STATA version 12.0 and Meta-Disc version 1.4. We calculated the summary statistics for sensitivity (Sen), specificity (Spe), positive and negative likelihood ratio (LR+/LR–), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curve. Results Ten studies that met al inclusion criteria were included in the meta-analysis. A total of 608 ma-lignant breast lesions and 1292 benign breast tumors were assessed. Al breast lesions were histological y confirmed after RTE. The pooled Sen was 0.83 (95% CI = 0.79–0.86); the pooled Spe was 0.86 (95% CI = 0.84–0.88). The pooled LR+ was 9.87 (95% CI = 2.66–36.71); the pooled LR– was 0.20 (95% CI = 0.17–0.23). The pooled DOR of RTE for the diagnosis of breast cancer was 62.21 (95% CI = 33.88–114.24). The area under the SROC curve was 0.9334 (standard error = 0.00125). We found no evidence of publica-tion bias (t = –0.57, P = 0.582). Conclusion RTE may have high diagnostic accuracy for the dif erential diagnosis of benign and malig-nant breast tumors. RTE may be a good tool for breast cancer diagnosis.

  20. [PRIMARY STUDY ON IMPLANT COVERAGE WITH LOCAL SOFT TISSUE IN IMMEDIATE IMPLANT-BASED BREAST RECONSTRUCTION].

    Science.gov (United States)

    Li, Guangxue; Mu, Lan; Liu, Yan; Yang, Kai; Peng, Zhe; Bi, Ye

    2016-03-01

    To explore the method of implant coverage with local soft tissue in immediate implant-based breast reconstruction and to evaluate the early effectiveness. Between April 2014 and August 2015, 11 patients with breast cancer underwent immediate breast reconstruction with implants after mastectomy, and the clinical data were reviewed retrospectively. The age ranged 29-48 years (mean, 36 years). The disease duration was from 7 days to 12 months (median, 3 months). According to tumor staging, 3 cases were rated as T(is)N0M0, 4 cases as T1N0M0, and 4 cases as T2N0M0. The implants were covered with local soft tissue according to the volume of mastectomy and contralateral breast size, including pectoralis major myocutaneous flaps with inframammary adipofasical flaps (3 cases), with serratus anterior fascial flap (5 cases), with rectus sheath fascial flap (1 case), and with serratus anterior fascial flap and rectus sheath fascial flap (2 cases). The size of pectoralis major myocutaneous flaps ranged from 15 cm x 9 cm to 20 cm x 15 cm, and the serratus anterior fascial flaps from 10 cm x 8 cm to 15 cm x 10 cm, and the rectus sheath fascial flap from 8 cm x 6 cm to 10 cm x 8 cm. One patient had partial nipple necrosis postoperatively and was cured, and no other postoperative complications of hematoma, infection, or implant exposure was found. The patients were followed up 4-13 months (median, 8 months). The reconstructive outcomes were excellent in 10 cases and good in 1 case, with an excellent and good rate of 100%. During follow-up, no rupture or exposure of the implant was observed; capsular contracture (Baker grade II) occurred in 1 case. Adequate coverage of implants with different local soft tissue flaps can achieve satisfactory early effectiveness in immediate implant-based breast reconstruction after mastectomy.

  1. Postoperative Expansion is not a Primary Cause of Infection in Immediate Breast Reconstruction with Tissue Expanders.

    Science.gov (United States)

    Avraham, Tomer; Weichman, Katie E; Wilson, Stelios; Weinstein, Andrew; Haddock, Nicholas T; Szpalski, Caroline; Choi, Mihye; Karp, Nolan S

    2015-01-01

    Perioperative infection is the most common and dreaded complication associated with tissue expander (TE) breast reconstruction. Historically, the expansion period was thought to be the time of greatest hazard to the implant. However, recent institutional observations suggest infectious complications occur prior to expansion. This investigation, therefore, was conducted to determine the timing of infectious complications associated with two-stage TE breast reconstructions. Following IRB approval, a retrospective review of all consecutive two-stage immediate TE breast reconstructions at a single institution from November 2007 to November 2011 was conducted. Reconstructions were then divided into two cohorts: those suffering infectious complications and those that did not. Infectious complications including minor cellulitis, major cellulitis, abscess drainage, and explantation were identified. Various operative and patient variables were evaluated in comparison. Eight hundred ninety immediate two-stage TE breast reconstructions met inclusion criteria. Patients suffering infection were older (55.4 years versus 49.3 years; p breast reconstructions are significant and occur mostly prior to the start of expansion. Thus, challenging the conventional wisdom that instrumentation during expander filling as the primary cause of implant infections. Possible etiologic factors include greater age, therapeutic mastectomy versus prophylactic mastectomy, larger initial TE fill, and the use of ADM. © 2015 Wiley Periodicals, Inc.

  2. IMMUNOHISTOCHEMICAL OBSERVATION OF MACROPHAGE COLONY STIMULATING FACTOR AND ITS RECEPTOR IN BREAST CANCER AND HEPATOMA TISSUES

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To study the potential role of cellular macrophageolony-stimulating factor (cM-CSF) and cellular macrophage colony-stimulating factor receptor (cM-CSF-R) with breast cancer and hepatoma and search the way for clinical application. Methods: Frozen surgical specimens from 48 breast cancer patients, including 29 cases of histological grade II and 19 eases of grade III, and 16 hepatoma patients were investigated by Avidin Biotin Complex (ABC) immunohistochemical assay with anti-M-CSF monoclonal antibody (Mab) and anti-M-CSF-R Mab. Pathohistological examination was performed as well. Results: cM-CSF and cM-CSF-R were detected in tested specimens. The expression levels of cM-CSF and cM-CSF-R in grade III group were higher than in grade II group and more higher than control group hyperplasia of breast. Hepatoma tissues also showed higher expression level of cM-CSF and cM-CSF-R than normal adult and fetal liver. Conclusion: Breast cancer and hepatoma tissues presented higher expression levels of cM-CSF and cM-CSF-R than control and expression level might be related with tumor's process.

  3. Concentration of Cd, Pb, Hg, and Se in Different Parts of Human Breast Cancer Tissues

    Directory of Open Access Journals (Sweden)

    Mehrnoosh Mohammadi

    2014-01-01

    Full Text Available Breast cancer is the major cause of cancer morbidity and mortality between women in the world. Metals involved in environmental toxicology are closely related to tumor growth and cancer. On the other hand, some metals such as selenium have anticarcinogenic properties. The aim of this study is to determine the concentration of cadmium, lead, mercury, and selenium in separated parts of tegmen, tumor, tumor adiposity, and tegmen adiposity of 14 breast cancer tissues which have been analyzed by graphite furnace atomic absorption (AA-670 and ICP-OES (ULTIMA 2CE. Our results show that Se and Hg have maximum and minimum concentration, respectively. Statistical analysis reveals no significant differences between metal accumulations in different parts of cancer tissues (P>0.05 and this observation might be due to the close relation of separated parts of fatty breast organ. Thus, we could conclude that a high level of these heavy metals is accumulated in Iranian cancerous breasts and their presence can be one of the reasons of cancer appearance.

  4. Adipose tissue omega-3 and omega-6 fatty acid content and breast cancer in the euramic study

    NARCIS (Netherlands)

    Simonsen, N.; Veer, P. van 't; Strain, J.J.; Martin-Moreno, J.M.; Huttunen, J.K.; Navajas, J.F.-C.; Martin, B.C.; Thamm, M.; Kardinaal, A.F.M.; Kok, F.J.; Kohlmeier, L.

    1998-01-01

    The fatty acid content of adipose tissue in postmenopausal breast cancer cases and controls from five European countries in the European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Cancer (EURAMIC) breast cancer study (1991-1992) was used to explore the hypothesis that

  5. Next Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer Tissue Specimens for Enhanced Clinical Guidance

    Science.gov (United States)

    2016-07-01

    AWARD NUMBER: W81XWH- 14-1-0192 TITLE: Next-Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer...DATES COVERED 4. TITLE AND SUBTITLE Next-Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer Tissue

  6. Adipose tissue omega-3 and omega-6 fatty acid content and breast cancer in the euramic study

    NARCIS (Netherlands)

    Simonsen, N.; Veer, P. van 't; Strain, J.J.; Martin-Moreno, J.M.; Huttunen, J.K.; Navajas, J.F.-C.; Martin, B.C.; Thamm, M.; Kardinaal, A.F.M.; Kok, F.J.; Kohlmeier, L.

    1998-01-01

    The fatty acid content of adipose tissue in postmenopausal breast cancer cases and controls from five European countries in the European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Cancer (EURAMIC) breast cancer study (1991-1992) was used to explore the hypothesis that fa

  7. The fractional viscoelastic response of human breast tissue cells

    Science.gov (United States)

    Carmichael, B.; Babahosseini, H.; Mahmoodi, S. N.; Agah, M.

    2015-07-01

    The mechanical response of a living cell is notoriously complicated. The complex, heterogeneous characteristics of cellular structure introduce difficulties that simple linear models of viscoelasticity cannot overcome, particularly at deep indentation depths. Herein, a nano-scale stress-relaxation analysis performed with an atomic force microscope reveals that isolated human breast cells do not exhibit simple exponential relaxation capable of being modeled by the standard linear solid (SLS) model. Therefore, this work proposes the application of the fractional Zener (FZ) model of viscoelasticity to extract mechanical parameters from the entire relaxation response, improving upon existing physical techniques to probe isolated cells. The FZ model introduces a new parameter that describes the fractional time-derivative dependence of the response. The results show an exceptional increase in conformance to the experimental data compared to that predicted by the SLS model, and the order of the fractional derivative (α) is remarkably homogeneous across the populations, with a median value of 0.48 ± 0.06 for the malignant population and 0.51 ± 0.07 for the benign. The cells’ responses exhibit power-law behavior and complexity not associated with simple relaxation (SLS, α = 1) that supports the application of a fractional model. The distributions of some of the FZ parameters also preserve the distinction between the malignant and benign sample populations seen from the linear model and previous results while including the contribution of fast-relaxation behavior. The resulting viscosity, measured by a composite relaxation time, exhibits considerably less dispersion due to residual error than the distribution generated by the linear model and therefore serves as a more powerful marker for cell differentiation.

  8. ROC analysis of ultrasound tissue characterization classifiers for breast cancer diagnosis.

    Science.gov (United States)

    Gefen, Smadar; Tretiak, Oleh J; Piccoli, Catherine W; Donohue, Kevin D; Petropulu, Athina P; Shankar, P Mohana; Dumane, Vishruta A; Huang, Lexun; Kutay, M Alper; Genis, Vladimir; Forsberg, Flemming; Reid, John M; Goldberg, Barry B

    2003-02-01

    Breast cancer diagnosis through ultrasound tissue characterization was studied using receiver operating characteristic (ROC) analysis of combinations of acoustic features, patient age, and radiological findings. A feature fusion method was devised that operates even if only partial diagnostic data are available. The ROC methodology uses ordinal dominance theory and bootstrap resampling to evaluate A(z) and confidence intervals in simple as well as paired data analyses. The combined diagnostic feature had an A(z) of 0.96 with a confidence interval of at a significance level of 0.05. The combined features show statistically significant improvement over prebiopsy radiological findings. These results indicate that ultrasound tissue characterization, in combination with patient record and clinical findings, may greatly reduce the need to perform biopsies of benign breast lesions.

  9. Genetic variations in FSH action affect sex hormone levels and breast tissue size in infant girls

    DEFF Research Database (Denmark)

    Henriksen, Louise Scheutz; Hagen, Casper P; Assens, Maria

    2016-01-01

    , especially FSHR -29G>A and FSHR 2039A>G, affect female hormone profile and glandular breast tissue development already during minipuberty. Thus, genetic variations of FSH signaling appear to determine the individual set point of the hypothalamic-pituitary-gonadal axis already early in life.......Context: Single nucleotide polymorphisms altering FSH action (FSHB -211G>T, FSHR -29G>A, and FSHR 2039A>G) are associated with peripubertal and adult levels of reproductive hormones and age at pubertal onset in girls. Objective: To investigate whether genetic polymorphisms altering FSH action...... present in homozygotes. FSHB -211T carriers had smaller breast tissue size than girls who without a minor allele; GT+TT 10.5 (confidence interval 9.4 -11.5) mm vs GG 12.1 (confidence interval 11.4-12.8) mm, P = .014. Conclusions: Our study indicates that 3 genetic polymorphisms altering FSH action...

  10. Multivariate analysis of the scattering profiles of healthy and pathological human breast tissues

    Energy Technology Data Exchange (ETDEWEB)

    Conceicao, A.L.C.; Antoniassi, M. [Departamento de Fisica e Matematica, FFCLRP, Universidade de Sao Paulo, Ribeirao Preto 14040-901, Sao Paulo (Brazil); Cunha, D.M. [Instituto de Fisica, Universidade Federal de Uberlandia, 38400-902, Uberlandia, Minas Gerais (Brazil); Ribeiro-Silva, A. [Departamento de Patologia, HCFMRP, Universidade de Sao Paulo, Ribeirao Preto 14040-901, Sao Paulo (Brazil); Poletti, M.E., E-mail: poletti@ffclrp.usp.br [Departamento de Fisica e Matematica, FFCLRP, Universidade de Sao Paulo, Ribeirao Preto 14040-901, Sao Paulo (Brazil)

    2011-10-01

    Scattering profiles of 106 healthy and pathological human breast samples were obtained using the angular dispersive X-ray scattering technique (AD-XRD) and synchrotron radiation covering the momentum transfer interval of 0.7 nm{sup -1}{<=}q(=4{pi} sin({theta}/2)/{lambda}){<=}70.5 nm{sup -1}. Multivariate analysis in the form of discriminant analysis was applied over the whole scattering profile curve of each sample in order to build a model for breast tissue classification. The classification results were validated and compared with histological sample classification obtained by microscopy analysis. Finally, the model allows classifying correctly 91.5% of the samples and presented values of 98.5%, 89.7% and 0.90 for sensitivity, specificity and Cohen's {kappa}, respectively, in correctly differentiating between healthy and pathological tissues.

  11. Tryptophan and its metabolite concentrations in human plasma and breast milk during the perinatal period.

    Directory of Open Access Journals (Sweden)

    Kamimura,Shigehito

    1991-04-01

    Full Text Available Concentrations of tryptophan (free and protein bound and its metabolites in plasma of maternal vein at delivery, umbilical vein, umbilical artery, neonatal vein and breast milk were determined by high performance liquid chromatography. The plasma levels of tryptophan and most of its metabolites in umbilical vein and artery were significantly higher than those in maternal vein. The concentration of total tryptophan in plasma of neonatal vein showed marked decrease at 24 h after birth in comparison with that at birth, but the total kynurenine concentration was not decreased in plasma of neonatal vein. The colostrum contained a high level of total tryptophan. There were high ratios of free to total tryptophan in colostrum, transitional and mature milk. In the blood, ratios of free to total of tryptophan and kynurenine were kept at constant level throughout the perinatal period.

  12. Associations of persistent organic pollutants in serum and adipose tissue with breast cancer prognostic markers.

    Science.gov (United States)

    Arrebola, J P; Fernández-Rodríguez, M; Artacho-Cordón, F; Garde, C; Perez-Carrascosa, F; Linares, I; Tovar, I; González-Alzaga, B; Expósito, J; Torne, P; Fernández, M F; Olea, N

    2016-10-01

    This study aimed to evaluate associations between exposure to a group of persistent organic pollutants, measured in both adipose tissue and serum samples from breast cancer patients, and a set of tumor prognostic markers. The study population comprised 103 breast cancer patients recruited in Granada, Southern Spain. Data for tumor prognostic markers were retrieved from hospital clinical records and socio-demographic information was gathered by questionnaire. Persistent organic pollutants were quantified by gas chromatography with electron capture detection. Exposure levels were categorized in quartiles, and associations were evaluated using unconditional logistic regression. Adipose tissue HCB concentrations were associated positively with ER and PR expression (p-trends=0.044 and 0.005, respectively) and negatively with E-Cadherin and p53 expression (p-trends=0.012 and 0.027, respectively). PCB-180 adipose tissue concentrations were positively associated with HER2 expression (p-trend=0.036). Serum PCB-138 concentrations were positively associated with ER and PR expression (p-trends=0.052 and 0.042, respectively). The risk of p53 expression was higher among women in the lowest quartile of serum PCB-138 concentrations, but no significant trend was observed (p-trend=0.161). These findings indicate that human exposure to certain persistent organic pollutants might be related to breast cancer aggressiveness. We also highlight the influence on exposure assessment of the biological matrix selected, given that both serum and adipose tissue might yield relevant information on breast cancer prognosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Non Invasive XRF Analysis of Human Hair for Health State Determination of Breast Tissue

    OpenAIRE

    Maziar, Asghar; Shahbazi-Gahrouei, Daryoush; Tavakoli, Mohammad Bagher; CHANGIZI, Vahid

    2015-01-01

    Background: Using hair samples to analyze the trace element concentrations is of interest among many researchers. X-ray fluorescence (XRF) and X-ray diffraction (XRD) are the most common methods in studying the structure and concentration of elements of tissues and also crystalline materials, using low energy X-ray. Objectives: In the present study, the detection ability of Wave Length X-ray Fluorescence (WLXRF) of breast cancer at early stages was evaluated and the results were compared with...

  14. Characterization of benign and malignant solid breast masses: comparison of conventional US and tissue harmonic imaging.

    Science.gov (United States)

    Cha, Joo Hee; Moon, Woo Kyung; Cho, Nariya; Kim, Sun Mi; Park, Seong Ho; Han, Boo-Kyung; Choe, Yeon Hyeon; Park, Jeong Mi; Im, Jung-Gi

    2007-01-01

    To prospectively compare the diagnostic performance of radiologists by using conventional ultrasonography (US) and tissue harmonic imaging for the differentiation of benign from malignant solid breast masses, with histologic results used as the reference standard. The study was approved by the institutional review board, and informed consent was obtained from all patients. Images were obtained with conventional US and tissue harmonic imaging in 88 patients (age range, 25-67 years; mean age, 45 years) with 91 solid breast masses (30 cancers and 61 benign lesions) before excisional or needle biopsy. Three experienced radiologists, who did not perform the examinations, independently analyzed the US findings and provided a level of suspicion to indicate the probability of malignancy. Results were evaluated by using kappa statistics and receiver operating characteristic (ROC) analyses. Regarding the descriptions of US findings, echogenicity (kappa=0.205) was the most discordant between conventional US and tissue harmonic imaging, followed by margin (kappa=0.495), lesion boundary (kappa=0.495), calcifications (kappa=0.537), posterior acoustic transmission (kappa=0.546), echotexture (kappa=0.586), shape (kappa=0.591), and orientation (kappa=0.594). The area under the ROC curve (Az) for conventional US and tissue harmonic imaging was 0.84 and 0.79, respectively, for reader 1; 0.88 and 0.85, respectively, for reader 2; and 0.91 and 0.89, respectively, for reader 3. The overall Az value for the three readers was 0.88 for conventional US and 0.84 for tissue harmonic imaging (95% confidence interval: -0.0950, 0.1646; P=.595). The performance of the radiologists with respect to the characterization of solid breast masses as benign or malignant was not significantly improved with tissue harmonic imaging. Copyright (c) RSNA, 2006.

  15. Role of deregulated microRNAs in breast cancer progression using FFPE tissue.

    Directory of Open Access Journals (Sweden)

    Liang Chen

    Full Text Available MicroRNAs (miRNAs contribute to cancer initiation and progression by silencing the expression of their target genes, causing either mRNA molecule degradation or translational inhibition. Intraductal epithelial proliferations of the breast are histologically and clinically classified into normal, atypical ductal hyperplasia (ADH, ductal carcinoma in situ (DCIS and invasive ductal carcinoma (IDC. To better understand the progression of ductal breast cancer development, we attempt to identify deregulated miRNAs in this process using Formalin-Fixed, Paraffin-Embedded (FFPE tissues from breast cancer patients. Following tissue microdissection, we obtained 8 normal, 4 ADH, 6 DCIS and 7 IDC samples, which were subject to RNA isolation and miRNA expression profiling analysis. We found that miR-21, miR-200b/c, miR-141, and miR-183 were consistently up-regulated in ADH, DCIS and IDC compared to normal, while miR-557 was uniquely down-regulated in DCIS. Interestingly, the most significant miRNA deregulations occurred during the transition from normal to ADH. However, the data did not reveal a step-wise miRNA alteration among discrete steps along tumor progression, which is in accordance with previous reports of mRNA profiling of different stages of breast cancer. Furthermore, the expression of MSH2 and SMAD7, two important molecules involving TGF-β pathway, was restored following miR-21 knockdown in both MCF-7 and Hs578T breast cancer cells. In this study, we have not only identified a number of potential candidate miRNAs for breast cancer, but also found that deregulation of miRNA expression during breast tumorigenesis might be an early event since it occurred significantly during normal to ADH transition. Consequently, we have demonstrated the feasibility of miRNA expression profiling analysis using archived FFPE tissues, typically with rich clinical information, as a means of miRNA biomarker discovery.

  16. Correlations of trace elements in breast human tissues: Evaluation of spatial distribution using {mu}-XRF

    Energy Technology Data Exchange (ETDEWEB)

    Piacenti da Silva, Marina; Silva, Deisy Mara da; Ribeiro-Silva, Alfredo; Poletti, Martin Eduardo [Departamento de Fisica, FFCLRP/USP, Av. dos Bandeirantes n. 3900, 14040-901 Ribeirao Preto - SP (Brazil); Departamento de Patologia, HCFM/USP, Av. dos Bandeirantes n. 3900, 14040-901 Ribeirao Preto - SP (Brazil); Departamento de Fisica, FFCLRP/USP, Av. dos Bandeirantes n. 3900, 14040-901 Ribeirao Preto - SP (Brazil)

    2012-05-17

    The aim of this work is to investigate microscopic correlations between trace elements in breast human tissues. A synchrotron X-ray fluorescence microprobe system ({mu}-XRF) was used to obtain two-dimensional distribution of trace element Ca, Fe, Cu and Zn in normal (6 samples) and malignant (14 samples) breast tissues. The experiment was performed in X-ray Fluorescence beam line at Laboratorio Nacional de Luz Sincrotron (LNLS), Campinas, Brazil. The white microbeam was generated with a fine conical capillary with a 20 {mu}m output diameter. The samples were supported on a XYZ table. An optical microscope with motorized zoom was used for sample positioning and choice the area to be scanned. Automatic two-dimensional scans were programmed and performed with steps of 30 {mu}m in each direction (x, y) on the selected area. The fluorescence signals were recorded using a Si(Li) detector, positioned at 90 degrees with respect to the incident beam, with a collection time of 10 s per point. The elemental maps obtained from each sample were overlap to observe correlation between trace elements. Qualitative results showed that the pairs of elements Ca-Zn and Fe-Cu could to be correlated in malignant breast tissues. Quantitative results, achieved by Spearman correlation tests, indicate that there is a spatial correlation between these pairs of elements (p < 0.001) suggesting the importance of these elements in metabolic processes associated with the development of the tumor.

  17. Relationship between crown-like structures and sex-steroid hormones in breast adipose tissue and serum among postmenopausal breast cancer patients.

    Science.gov (United States)

    Mullooly, Maeve; Yang, Hannah P; Falk, Roni T; Nyante, Sarah J; Cora, Renata; Pfeiffer, Ruth M; Radisky, Derek C; Visscher, Daniel W; Hartmann, Lynn C; Carter, Jodi M; Degnim, Amy C; Stanczyk, Frank Z; Figueroa, Jonine D; Garcia-Closas, Montserrat; Lissowska, Jolanta; Troester, Melissa A; Hewitt, Stephen M; Brinton, Louise A; Sherman, Mark E; Gierach, Gretchen L

    2017-01-19

    Postmenopausal obesity is associated with increased circulating levels of androgens and estrogens and elevated breast cancer risk. Crown-like structures (CLS; microscopic foci of dying adipocytes surrounded by macrophages) are proposed to represent sites of increased aromatization of androgens to estrogens. Accordingly, we examined relationships between CLS and sex-steroid hormones in breast adipose tissue and serum from postmenopausal breast cancer patients. Formalin-fixed paraffin embedded benign breast tissues collected for research from postmenopausal women (n = 83) diagnosed with invasive breast cancer in the Polish Breast Cancer Study (PBCS) were evaluated. Tissues were immunohistochemically stained for CD68 to determine the presence of CLS per unit area of adipose tissue. Relationships were assessed between CD68 density and CLS and previously reported sex-steroid hormones quantified using radioimmunoassays in serum taken at the time of diagnosis and in fresh frozen adipose tissue taken at the time of surgery. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the relationships between hormones (in tertiles) and CLS. CLS were observed in 36% of benign breast tissues, with a higher frequency among obese versus lean women (54% versus 17%, p = 0.03). Detection of CLS was not related to individual hormone levels or breast tumor pathology characteristics. However, detection of CLS was associated with hormone ratios. Compared with women in the highest tertile of estrone:androstenedione ratio in fat, those in the lowest tertile were less likely to have CLS (OR 0.12, 95% CI 0.03-0.59). A similar pattern was observed with estradiol:testosterone ratio in serum and CLS (lowest versus highest tertile, OR 0.18, 95% CI 0.04-0.72). CLS were more frequently identified in the breast fat of obese women and were associated with increased ratios of select estrogens:androgens in the blood and tissues, but not with

  18. Serum/plasma DNA methylation pattern and early detection of breast cancer

    Directory of Open Access Journals (Sweden)

    Arootin Gharibiyan

    2015-01-01

    Full Text Available Breast cancer is the most common cancer among women. With its fatality rate reduced significantly if diagnosed early, developing cost-effective, noninvasive methods of early detection is highly investigated. Currently, mammography with magnetic resonance imaging is considered the optimal method of early detection in women who are at a significantly raised risk of developing breast cancer. Due to environmental effects and life-style changes in recent years, elevation of the risk of cancer incidents in lower risk populations is observed and therefore, the development of a relatively easy-performed and low-cost method for early detection of cancer in general and breast cancer in particular is needed. Serum-based analysis techniques have been quite popular subject of research recently as they can be performed with low technical knowledge, become automated and are cheap. In the present article, we have reviewed the literature related to the use of DNA methylation-detection based techniques for diagnosis of early-stage breast cancer using serum or plasma circulating tumor DNA and their power as a future biomarker. A reference to all genes that is reported to be differentially methylated in breast cancer accompanies the article.

  19. Combination of cold atmospheric plasma and iron nanoparticles in breast cancer: gene expression and apoptosis study

    Directory of Open Access Journals (Sweden)

    Jalili A

    2016-09-01

    Full Text Available Azam Jalili,1 Shiva Irani,1 Reza Mirfakhraie2 1Department of Biology, Science and Research Branch, Islamic Azad University, 2Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran Background: Current cancer treatments have unexpected side effects of which the death of normal cells is one. In some cancers, iron nanoparticles (NPs can be subjected to diagnosis and passive targeting treatment. Cold atmospheric plasma (CAP has a proven induction of selective cell death ability. In this study, we have attempted to analyze the synergy between CAP and iron NPs in human breast adenocarcinoma cells (MCF-7.Materials and methods: In vitro cytotoxicity of CAP treatment and NPs in cells measured by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and cell death was shown by 4',6-diamidino-2-phenylindole and annexin V staining. Fluctuations in BAX and BCL-2 gene expression were investigated by means of real-time polymerase chain reaction.Results: MTT assay results showed that combination of plasma and iron NPs decreased the viability of cancer cells significantly (P<0.05. Real-time analysis showed that the combination therapy induced shifting the BAX/BCL-2 ratio in favor of apoptosis.Conclusion: Our data indicate that synergy between CAP and iron NPs can be applied in breast cancer treatment selectively. Keywords: breast cancer, cold atmospheric plasma, iron nanoparticles, BAX, BCL-2

  20. von Willebrand factor antigen levels in plasma of patients with malignant breast disease

    Directory of Open Access Journals (Sweden)

    L.M. Röhsig

    2001-09-01

    Full Text Available von Willebrand factor (vWF is a protein that mediates platelet adherence to the subendothelium during primary hemostasis. High plasma vWF concentrations have been reported in patients with various types of cancer, such as head and neck, laryngeal and prostatic cancer, probably representing an acute phase reactant. In the present study we determined the plasma levels of vWF antigen (vWF:Ag by quantitative immunoelectrophoresis in 128 female patients with breast cancer as well as in 47 women with benign breast disease and in 27 healthy female controls. The levels of vWF:Ag were 170.7 ± 78 U/dl in patients with cancer, 148.4 ± 59 U/dl in patients with benign disease and 130.6 ± 45 U/dl in controls (P<0.005. We also detected a significant increase in the levels of vWF:Ag (P<0.0001 in patients with advanced stages of the disease (stage IV = 263.3 ± 113 U/dl, stage IIIB = 194.0 ± 44 U/dl as compared to those with earlier stages of the disease (stage I = 155.3 ± 65 U/dl, stage IIA = 146.9 ± 75 U/dl. In conclusion, vWF levels were increased in plasma of patients with malignant breast disease, and these levels correlated with tumor progression.

  1. The use of Compton scattering to differentiate between classifications of normal and diseased breast tissue

    Energy Technology Data Exchange (ETDEWEB)

    Ryan, Elaine A; Farquharson, Michael J; Flinton, David M [School of Allied Health Sciences, City University, Charterhouse Square, London EC1M 6PA (United Kingdom)

    2005-07-21

    This study describes a technique for measuring the electron density of breast tissue utilizing Compton scattered photons. The K{sub {alpha}}{sub 2} line from a tungsten target industrial x-ray tube (57.97 keV) was used and the scattered x-rays collected at an angle of 30{sup 0}. At this angle the Compton and coherent photon peaks can be resolved using an energy dispersive detector and a peak fitting algorithm. The system was calibrated using solutions of known electron density. The results obtained from a pilot study of 22 tissues are presented. The tissue samples investigated comprise four different tissue classifications: adipose, malignancy, fibroadenoma and fibrocystic change (FCC). It is shown that there is a difference between adipose and malignant tissue, to a value of 9.0%, and between adipose and FCC, to a value of 12.7%. These figures are found to be significant by statistical analysis. The differences between adipose and fibroadenoma tissues (2.2%) and between malignancy and FCC (3.4%) are not significant. It is hypothesized that the alteration in glucose uptake within malignant cells may cause these tissues to have an elevated electron density. The fibrotic nature of tissue that has undergone FCC gives the highest measure of all tissue types.

  2. The use of Compton scattering to differentiate between classifications of normal and diseased breast tissue

    Science.gov (United States)

    Ryan, Elaine A.; Farquharson, Michael J.; Flinton, David M.

    2005-07-01

    This study describes a technique for measuring the electron density of breast tissue utilizing Compton scattered photons. The Kα2 line from a tungsten target industrial x-ray tube (57.97 keV) was used and the scattered x-rays collected at an angle of 30°. At this angle the Compton and coherent photon peaks can be resolved using an energy dispersive detector and a peak fitting algorithm. The system was calibrated using solutions of known electron density. The results obtained from a pilot study of 22 tissues are presented. The tissue samples investigated comprise four different tissue classifications: adipose, malignancy, fibroadenoma and fibrocystic change (FCC). It is shown that there is a difference between adipose and malignant tissue, to a value of 9.0%, and between adipose and FCC, to a value of 12.7%. These figures are found to be significant by statistical analysis. The differences between adipose and fibroadenoma tissues (2.2%) and between malignancy and FCC (3.4%) are not significant. It is hypothesized that the alteration in glucose uptake within malignant cells may cause these tissues to have an elevated electron density. The fibrotic nature of tissue that has undergone FCC gives the highest measure of all tissue types.

  3. Parametrization histological grade white adipose tissue of the breast by the cubic spline interpolation

    Science.gov (United States)

    Martinez, Leslie A.; Narea, Freddy J.; Cedeño, Fernando; Muñoz, Aaron A.; Reigosa, Aldo; Bravo, Kelly

    2013-11-01

    The noninvasive optical techniques have attracted considerable interest in recent years, because these techniques provide lot of information on the structure and composition of biological tissues more quickly and painlessly, in this study classifies the degrees of histological differentiation of neoplastic tissue of the breast in white adipose tissue samples through numerical pametrización of the diffuse reflection spectra using the Fourier series approximation. The white adipose tissue is irradiated with the spectrophotometer MiniScan XEplus and it from a mastectomy of patients with aged 38 and 50 who have a cancer lesion in the breast. The samples were provided by the pathologist with theirs medical report, it which we indicate the histological grade of tumor. We performed a parameterization algorithm where the classification criterion is the modulus of the minimum difference between the numerical approximation coefficients ai and average numerical approximation coefficients obtained for each histological grade ¯ al. Is confirmed that the cubic spline interpolation this low-power computing lets classified into histological grades with 91% certainty the tissues under study from |ai - ¯ al|

  4. Levels of tissue inhibitor of metalloproteinases 1 in plasma and urine frompatients with bladder cancer

    DEFF Research Database (Denmark)

    Holten Andersen, MN; Brunner, N; Nielsen, HJ;

    2006-01-01

    Aim: To assess the potential use of plasma and urine levels of tissue inhibitor of metalloproteinases 1 (TIMP-1) in urothelial cancer. Methods: TIMP-1 levels were determined in urine and plasma from healthy donors (n=26), patients with bacterial bladder infection (n=24), urothelial bladder adenoma...

  5. Levels of tissue inhibitor of metalloproteinases 1 in plasma and urine from patients with cancer

    DEFF Research Database (Denmark)

    Holten-Andersen, Mads Nikolaj; Brünner, Nils; Nielsen, Hans Jørgen;

    2006-01-01

    AIM: To assess the potential use of plasma and urine levels of tissue inhibitor of metalloproteinases 1 (TIMP-1) in urothelial cancer. METHODS: TIMP-1 levels were determined in urine and plasma from healthy donors (n=26), patients with bacterial bladder infection (n=24), urothelial bladder adenoma...

  6. Levels of tissue inhibitor of metalloproteinases 1 in plasma and urine from patients with cancer

    DEFF Research Database (Denmark)

    Holten-Andersen, Mads Nikolaj; Brünner, Nils; Nielsen, Hans Jørgen

    2006-01-01

    AIM: To assess the potential use of plasma and urine levels of tissue inhibitor of metalloproteinases 1 (TIMP-1) in urothelial cancer. METHODS: TIMP-1 levels were determined in urine and plasma from healthy donors (n=26), patients with bacterial bladder infection (n=24), urothelial bladder adenoma...

  7. Impact of Different Analytic Approaches on the Analysis of the Breast Fibroglandular Tissue Using Diffusion Weighted Imaging

    Directory of Open Access Journals (Sweden)

    Yoon Jung Choi

    2017-01-01

    Full Text Available Purpose. This study investigated the impact of the different region of interest (ROI approaches on measurement of apparent diffusion coefficient (ADC values in the breast firbroglandular tissue (FT. Methods. Breast MR images of 38 women diagnosed with unilateral breast cancer were studied. Percent density (PD and ADC were measured from the contralateral normal breast. Four different ROIs were used for ADC measurement. The measured PD and ADC were correlated. Results. Among the four ROIs, the manually placed small ROI on FT gave the highest mean ADC (ADC = 1839 ± 343 [×10−6 mm2/s], while measurement from the whole breast gave the lowest mean ADC (ADC = 933 ± 383 [×10−6 mm2/s]. The ADC measured from the whole breast was highly correlated with PD with r=0.95. In slice-to-slice comparison, the central slices with more FT had higher ADC values than the peripheral slices did, presumably due to less partial volume effect from fat. Conclusions. Our results indicated that the measured ADC heavily depends on the composition of breast tissue contained in the ROI used for the ADC measurements. Women with low breast density showing lower ADC values were most likely due to the partial volume effect of fatty tissues.

  8. Clinical and Prognostic Significance of Preoperative Plasma Fibrinogen Levels in Patients with Operable Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Yu Mei

    Full Text Available Elevated plasma fibrinogen levels are associated with tumor progression and poor outcomes in different cancer patients. The objective of this study was to investigate the clinical and prognostic value of preoperative plasma fibrinogen levels in patients with operable breast cancer.Two hundred and twenty-three patients diagnosed with breast cancer were retrospectively evaluated in this study. Plasma fibrinogen levels were examined before treatment and analyzed along with patient clinicopathological parameters, disease-free survival (DFS and overall survival (OS. Both univariate and multivariate analyses were performed to identify the clinicopathological parameters associated with DFS and OS.Elevated preoperative plasma fibrinogen levels were directly associated with age of diagnose (≤47 vs. >47, p<0.001, menopause (yes vs. no, p<0.001, tumor size (T1&T2 vs. T3&T4, p = 0.033, tumor stage (I vs. II vs. III, p = 0.034 and lymph node involvement (N = 0 vs. 1≤N≤3 vs. N≥4, p<0.001, but not with histological grade, molecular type and other Immunohistochemical parameters (ER, PR, HER2 and Ki-67. In a univariate survival analysis, tumor stage, tumor size, lymph node involvement (p<0.001/p<0.001 and plasma fibrinogen (p<0.001/p<0.001 levels were associated with disease-free and overall survival, but just lymph nodes involvement (p<0.001, hazard ratio [HR] = 2.9, 95% confidence interval [CI] = 1.6-5.3/p = 0.006, HR = 3.2, 95% CI = 1.4-7.3 and plasma fibrinogen levels (p = 0.006, HR = 3.4, 95% CI = 1.4-8.3/p = 0.002, HR = 10.1, 95% CI = 2.3-44.6 were associated with disease-free and overall survival in a multivariate survival analysis, respectively.This study demonstrates that elevated preoperative plasma fibrinogen levels are associated with breast cancer progression and are independently associated with a poor prognosis in patients with operable breast cancer.

  9. Diffusion-weighted imaging of normal fibroglandular breast tissue : influence of microperfusion and fat suppression technique on the apparent diffusion coefficient

    NARCIS (Netherlands)

    Baron, Paul; Dorrius, Monique D.; Kappert, Peter; Oudkerk, Matthijs; Sijens, Paul E.

    2010-01-01

    The influence of microperfusion and fat suppression technique on the apparent diffusion coefficient (ADC) values obtained with diffusion weighted imaging (DWI) of normal fibroglandular breast tissue was investigated. Seven volunteers (14 breasts) were scanned using diffusion weighting factors (b val

  10. Application of Small Angle X-ray Scattering (SAXS for Differentiation between Normal and Cancerous Breast Tissue

    Directory of Open Access Journals (Sweden)

    2005-07-01

    Full Text Available Introduction: Small angle, between 3° and 10°, X ray scattering is predominantly coherent giving rise to diffraction effects that can be observed as constructive and destructive interferences. These interferences carry information about the molecular structure of the tissue and hence can be used to identify changes that occur due to cancer. Method: In this study an energy dispersive X-ray diffraction method was used. The optimum scattering angle, determined from a series of measurements on adipose breast tissue at several angles from 4 to 7.3 degrees, was found to be 6.5°. Once optimized the system was used to measure the diffraction profiles (corrected scattered intensity versus momentum transfer of a total of 99 breast tissue samples. The samples were both normal and tumour samples. Results: Adipose tissue showed a sharp, high intensity peak at low momentum transfer values of approximately 1.1nm-1. Adipose tissue, mixed tissue (adipose & fibroglandular and tumor have peaks at different values of momentum transfer that can be used to identify the tissue. Benign and malignant breast tissues can also be differentiated by both peak positions and peak heights. It was also observed that the results were reproducible even after the tissue had been preserved at liquid nitrogen temperatures. Conclusion: We were able to differentiate between normal, benign and malignant breast tissues by using energy dispersive small angle x-ray scattering.

  11. Value of high-frequency ultrasonography with virtual touch tissue quantification in diagnosis of breast pure mucinous carcinomas

    Institute of Scientific and Technical Information of China (English)

    Jian Shi; Guang Yang; Jialing Wu; Wenlin Xu

    2012-01-01

    Objective: The aim of our study was to analyze the characters of breast pure mucinous carcinomas on highfrequency ultrasonography with virtual touch tissue quantification (VTQ). Methods: A total of 12 patients (with breast pure mucinous carcinomas) and a group of 30 patients (with adenofibroma of breast) underwent breast examination with high-frequency ultrasonography to analyze the characters of images, and with VTQ to analyze the elastic character. Results: In the conventional ultrasound imaging, statistical differences were found between two groups in the shape, the boundary and the internal echo of the lesions. In the VTQ, the mean of shearing wave speed (Vs) in pure mucinous carcinomas was less than in adenofibroma of breast. Conclusion: Conventional high-frequency ultrasonography combining with VTQ have significant value in diagnosis of breast pure mucinous carcinoma.

  12. Plasma polychlorinated biphenyl levels in Dutch preschool children either breast-fed or formula-fed during infancy

    NARCIS (Netherlands)

    Patandin, S; WeisglasKuperus, N; deRidder, MAJ; KoopmanEsseboom, C; vanStaveren, WA; vanderPaauw, CG; Sauer, PJJ

    1997-01-01

    Objectives. This study examined the influence of lactational and in utero exposure to polychlorinated biphenyls (PCBs) on plasma PCB levels in children. Methods. Plasma PCB levels were measured in 173 children at 3.5 years, of whom 91 were breast-fed and 82 were formula-fed in infancy. Results. Medi

  13. Impact of menopausal status on background parenchymal enhancement and fibroglandular tissue on breast MRI

    Energy Technology Data Exchange (ETDEWEB)

    King, Valencia [Memorial Sloan-Kettering Cancer Center, Department of Radiology, Breast Imaging Section, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Gu, Yajia [Fudan University Shanghai Cancer Center, Department of Radiology, Shanghai (China); Fudan University, Department of Oncology, Shanghai Medical College, Shanghai (China); Kaplan, Jennifer B.; Morris, Elizabeth A. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, Breast Imaging Section, New York, NY (United States); Brooks, Jennifer D.; Pike, Malcolm C. [Memorial Sloan-Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY (United States)

    2012-12-15

    To evaluate the effect of menopausal status on the background parenchymal enhancement (BPE) and amount of fibroglandular tissue (FGT) on breast MRI. Retrospective review identified 1,130 women who underwent screening breast MRI between July and November 2010. In 28 of these women, breast MRI was performed both at one time point while pre- and one time point while post-menopausal (median interval 49 months). Two independent readers blinded to menopausal status used categorical scales to rate BPE (minimal/mild/moderate/marked) and FGT (fatty/scattered/heterogeneously dense/dense). Consensus was reached when there was disagreement. The sign test was used to assess changes in rating categories, and the Spearman rank and Fisher's exact tests were used to measure correlations and associations between variables. Significant proportions of women demonstrated decreases in BPE and FGT on post-menopausal breast MRI (P = 0.0001 and P = 0.0009). BPE category was unchanged in 39 % (11/28) and decreased in 61 % (17/28) of women. FGT category was unchanged in 61 % (17/28) and decreased in 39 % (11/28) of women. Age, reason for menopause, or interval between MRIs had no significant impact on changes in BPE and FGT. On MRI, BPE, and FGT decrease after menopause in significant proportions of women; BPE decreases more than FGT. (orig.)

  14. Differences in oestrogen receptors in malignant and normal breast tissue as identified by the binding of a new synthetic progestogen.

    OpenAIRE

    Iqbal, M J; Colletta, A. A.; Houmayoun-Valyani, S. D.; Baum, M.

    1986-01-01

    Oestrogen receptor protein (ER) was detected in 9 of 11 samples of malignant breast tissue and 8 of 9 samples of normal breast tissue. Levels of cytosolic ER (ERc) in malignant breast were 21-1102 fmol mg-1 soluble protein (Kd 1.8 X 10(-9)-3.1 X 10(-8) mol l-1) and those of nucleosolic ER (ERn), 13-526 fmol mg-1 soluble protein (Kd 2.1 X 10(-9)-1.4 X 10(-8) mol l-1). In normal breast tissue ERc levels were 33-640 fmol mg-1 soluble protein (Kd 1.3 X 10(-10)-3.2 X 10(-9) mol l-1), ERn was detec...

  15. Content Based Mammogram Retrieval based on Breast Tissue Characterization using Statistical Features

    Directory of Open Access Journals (Sweden)

    K. Vaidehi

    2014-08-01

    Full Text Available The aim of the study is to retrieve the similar mammographic images based on the type of breast tissue density of the given query image. Statistical descriptors were extracted from the candidate blocks of the breast parenchyma. The mean of extracted features are fed into the SVM classifier for classification of the tissue density into any of the three classes namely dense, glandular and fatty and the classification accuracy obtained is 91.54%. After classification the mammogram images along with its feature vector are stored into three separate databases based on tissue type. Then K-means clustering algorithm is used to divide each database into 2 clusters. For content based retrieval of the mammograms based on the given query image, first the query image is classified into any of the three tissue class. Then the feature vector of the query image is compared with the two cluster centroids of the corresponding class, so as to confine the search within the closest cluster. Top 5 similar images are retrieved from its corresponding class database. Euclidean distance based k-NN is used for mammogram retrieval and this study obtained the highest precision rate ranging between 98 and 99%.

  16. Correlation of breast tissue histology and optical signatures to improve margin assessment techniques

    Science.gov (United States)

    Kennedy, Stephanie; Caldwell, Matthew; Bydlon, Torre; Mulvey, Christine; Mueller, Jenna; Wilke, Lee; Barry, William; Ramanujam, Nimmi; Geradts, Joseph

    2016-06-01

    Optical spectroscopy is sensitive to morphological composition and has potential applications in intraoperative margin assessment. Here, we evaluate ex vivo breast tissue and corresponding quantified hematoxylin & eosin images to correlate optical scattering signatures to tissue composition stratified by patient characteristics. Adipose sites (213) were characterized by their cell area and density. All other benign and malignant sites (181) were quantified using a grid method to determine composition. The relationships between mean reduced scattering coefficient (), and % adipose, % collagen, % glands, adipocyte cell area, and adipocyte density were investigated. These relationships were further stratified by age, menopausal status, body mass index (BMI), and breast density. We identified a positive correlation between and % collagen and a negative correlation between and age and BMI. Increased collagen corresponded to increased variability. In postmenopausal women, was similar regardless of fibroglandular content. Contributions from collagen and glands to were independent and equivalent in benign sites; glands showed a stronger positive correlation than collagen to in malignant sites. Our data suggest that scattering could differentiate highly scattering malignant from benign tissues in postmenopausal women. The relationship between scattering and tissue composition will support improved scattering models and technologies to enhance intraoperative optical margin assessment.

  17. Incorporation of conjugated linoleic acid and vaccenic acid into lipids from rat tissues and plasma

    DEFF Research Database (Denmark)

    Lund, Pia; Sejrsen, Kristen; Straarup, Ellen Marie

    2006-01-01

    The objective of this study was to determine the incorporation of conjugated linoleic acid (CLA) into triacylglycerols (TAG) and phospholipids (PL) of tissues and plasma, and to interpret the role of dietary-derived vaccenic acid (VA) in increasing the tissue content of CLA (c9,t11) and the influ...

  18. A comparative performance study characterizing breast tissue microarrays using standard RGB and multispectral imaging

    Science.gov (United States)

    Qi, Xin; Cukierski, William; Foran, David J.

    2010-02-01

    The lack of clear consensus over the utility of multispectral imaging (MSI) for bright-field imaging prompted our team to investigate the benefit of using MSI on breast tissue microarrays (TMA). We have conducted performance studies to compare MSI with standard bright-field imaging in hematoxylin stained breast tissue. The methodology has three components. The first extracts a region of interest using adaptive thresholding and morphological processing. The second performs texture feature extraction from a local binary pattern within each spectral channel and compared to features of co-occurrence matrix and texture feature coding in third component. The third component performs feature selection and classification. For each spectrum, exhaustive feature selection was used to search for the combination of features that yields the best classification accuracy. AdaBoost with a linear perceptron least-square classifier was applied. The spectra carrying the greatest discriminatory power were automatically chosen and a majority vote was used to make the final classification. 92 breast TMA discs were included in the study. Sensitivity of 0.96 and specificity of 0.89 were achieved on the multispectral data, compared with sensitivity of 0.83 and specificity of 0.85 on RGB data. MSI consistently achieved better classification results than those obtained using standard RGB images. While the benefits of MSI for unmixing multi-stained specimens are well documented, this study demonstrated statistically significant improvements in the automated analysis of single stained bright-field images.

  19. CT measurement of breast glandular tissue and its association with testicular cancer

    Energy Technology Data Exchange (ETDEWEB)

    Klang, Eyal [Tel Aviv University, Department of Radiology, Chaim Sheba Medical Center, Tel Aviv (Israel); The Chaim Sheba Medical Center, Tel Hashomer (Israel); Rozendorn, Noa; Raskin, Steve; Portnoy, Orith; Sklair, Miri; Marom, Edith M.; Konen, Eli; Amitai, Michal M. [Tel Aviv University, Department of Radiology, Chaim Sheba Medical Center, Tel Aviv (Israel)

    2017-02-15

    To evaluate the associations between breast glandular tissues diameters as determined by CT and b-hCG levels, histological types, tumour spread and prognosis in patients with testicular germ cell tumour. Ninety-four patients with pre-treatment CT scan and markers (b-hCG, AFP, LDH) were retrospectively collected. A radiologist measured diameters in all CT examinations and correlation between diameters and log (b-hCG) was assessed (Pearson's coefficient). The ability of measured diameters to predict lymphatic and distant haematogenous metastatic spread was evaluated (ROC curves). The associations between measured diameter cut-off values of 20 and 25 mm and International Germ Cell Cancer Collaborative Group (IGCCCG) classification, lymphatic and distant haematogenous metastatic spread and histological subtypes were evaluated (chi squared test). Breast glandular diameters correlated to log(b-hCG) (r = 0.579) and predicted distant haematogenous metastatic spread (AUC = 0.78). Worse prognosis (intermediate or poor IGCCCG) was shown for 20 mm (27.3 vs. 4.2 %, p = 0.005) and 25 mm (33.3 vs. 6.1 %, p = 0.014). A diameter of 25 mm was associated with non-seminoma (91.7 vs. 48.8 %, p = 0.005). Breast glandular tissue diameters correlated with log(b-hCG) and predicted distant haematogenous metastases. Twenty and 25 mm were associated with worse prognosis and 25 mm was able to distinguish between seminoma and non-seminoma. (orig.)

  20. Preservation of biomolecules in breast cancer tissue by a formalin-free histology system

    Directory of Open Access Journals (Sweden)

    Morales Azorides R

    2008-01-01

    Full Text Available Abstract Background The potential problems associated with the use of formalin in histology, such as health hazards, degradation of RNA and cross-linking of proteins are well recognized. We describe the utilization of a formalin-free fixation and processing system for tissue detection of two important biopredictors in breast cancer – estrogen receptor and HER2 – at the RNA and protein levels. Methods Parallel sections of 62 cases of breast cancer were fixed in an alcohol-based molecular fixative and in formalin. Molecular fixative samples were processed by a novel formalin-free microwave-assisted processing system that preserves DNA, RNA and proteins. Formalin-fixed samples were processed using the conventional method. Estrogen receptor was assessed by immunohistochemistry and real-time PCR. HER2 was assessed by immunohistochemistry, FISH, CISH and real-time PCR. Results The immunohistochemical reaction for estrogen receptor was similar in molecular- and formalin-fixed samples (Spearman Rank R = 0.83, p Conclusion The formalin-free tissue fixation and processing system is a practical platform for evaluation of biomolecular markers in breast cancer and it allows reliable DNA and RNA and protein studies.

  1. DETECTION AND CLINICAL SIGNIFICANCE OF THROMBOMODULIN IN BOTH PLASMA AND TISSUE EXTRACTS OF CANCER PATIENTS

    Institute of Scientific and Technical Information of China (English)

    许晓华; 卢兴国; 徐根波; 朱蕾; 黄连生

    2004-01-01

    Objective: To study the changes of thrombomodulin (TM) in both plasma and tissue extracts of cancer patients for evaluating its clinical significance. Methods: Plasma TM levels were measured by enzyme-linked immunosorbent assay (ELISA) in both plasma of 188 cancer patients and 24 cancer tissue extracts including their adjacent non-cancer tissues. Results: The plasma TM levels both in cancer patients and in metastasis patients were significantly higher than that in controls [(33.47±14.25)μg/L, (41.68±16.96)μg/L, vs(20.40±7.22)μg/L,P0.05). The TM levels in cancer tissue extracts were significantly lower than that in their adjacent non-cancer tissue extracts [(647.71±317.51)μg/L vs (1455.63±772.22)μg/L, P<0.01]. On the contrary, the plasma TM levels in these cancers were significantly higher than that in controls. Conclusion: The rise of plasma TM levels in cancer patients was associated with metastasis and diffusion of cancers. The TM levels can be served as an sensitive index for judging progression and metastasis of cancers.

  2. Compton scattering spectrum as a source of information of normal and neoplastic breast tissues' composition

    Energy Technology Data Exchange (ETDEWEB)

    Antoniassi, M.; Conceicao, A.L.C. [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, 14040-901 Sao Paulo (Brazil); Poletti, M.E., E-mail: poletti@ffclrp.usp.br [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, 14040-901 Sao Paulo (Brazil)

    2012-07-15

    In this work we measured X-ray scatter spectra from normal and neoplastic breast tissues using photon energy of 17.44 keV and a scattering angle of 90 Degree-Sign , in order to study the shape (FWHM) of the Compton peaks. The obtained results for FWHM were discussed in terms of composition and histological characteristics of each tissue type. The statistical analysis shows that the distribution of FWHM of normal adipose breast tissue clearly differs from all other investigated tissues. Comparison between experimental values of FWHM and effective atomic number revealed a strong correlation between them, showing that the FWHM values can be used to provide information about elemental composition of the tissues. - Highlights: Black-Right-Pointing-Pointer X-ray scatter spectra from normal and neoplastic breast tissues were measured. Black-Right-Pointing-Pointer Shape (FWHM) of Compton peak was related with elemental composition and characteristics of each tissue type. Black-Right-Pointing-Pointer A statistical hypothesis test showed clear differences between normal and neoplastic breast tissues. Black-Right-Pointing-Pointer There is a strong correlation between experimental values of FWHM and effective atomic number. Black-Right-Pointing-Pointer Shape (FWHM) of Compton peak can be used to provide information about elemental composition of the tissues.

  3. Rational use of plasma protein and tissue binding data in drug design.

    Science.gov (United States)

    Liu, Xingrong; Wright, Matthew; Hop, Cornelis E C A

    2014-10-23

    It is a commonly accepted assumption that only unbound drug molecules are available to interact with their targets. Therefore, one of the objectives in drug design is to optimize the compound structure to increase in vivo unbound drug concentration. In this review, theoretical analyses and experimental observations are presented to illustrate that low plasma protein binding does not necessarily lead to high in vivo unbound plasma concentration. Similarly, low brain tissue binding does not lead to high in vivo unbound brain tissue concentration. Instead, low intrinsic clearance leads to high in vivo unbound plasma concentration, and low efflux transport activity at the blood-brain barrier leads to high unbound brain concentration. Plasma protein and brain tissue binding are very important parameters in understanding pharmacokinetics, pharmacodynamics, and toxicities of drugs, but these parameters should not be targeted for optimization in drug design.

  4. Bone tissue response to plasma-nitrided titanium implant surfaces

    Directory of Open Access Journals (Sweden)

    Emanuela Prado FERRAZ

    2015-02-01

    Full Text Available A current goal of dental implant research is the development of titanium (Ti surfaces to improve osseointegration. Plasma nitriding treatments generate surfaces that favor osteoblast differentiation, a key event to the process of osteogenesis. Based on this, it is possible to hypothesize that plasma-nitrided Ti implants may positively impact osseointegration. Objective The aim of this study was to evaluate the in vivo bone response to Ti surfaces modified by plasma-nitriding treatments. Material and Methods Surface treatments consisted of 20% N2 and 80% H2, 450°C and 1.5 mbar during 1 h for planar and 3 h for hollow cathode. Untreated surface was used as control. Ten implants of each surface were placed into rabbit tibiae and 6 weeks post-implantation they were harvested for histological and histomorphometric analyses. Results Bone formation was observed in contact with all implants without statistically significant differences among the evaluated surfaces in terms of bone-to-implant contact, bone area between threads, and bone area within the mirror area. Conclusion Our results indicate that plasma nitriding treatments generate Ti implants that induce similar bone response to the untreated ones. Thus, as these treatments improve the physico-chemical properties of Ti without affecting its biocompatibility, they could be combined with modifications that favor bone formation in order to develop new implant surfaces.

  5. Bone tissue response to plasma-nitrided titanium implant surfaces.

    Science.gov (United States)

    Ferraz, Emanuela Prado; Sverzut, Alexander Tadeu; Freitas, Gileade Pereira; Sá, Juliana Carvalho; Alves, Clodomiro; Beloti, Marcio Mateus; Rosa, Adalberto Luiz

    2015-01-01

    A current goal of dental implant research is the development of titanium (Ti) surfaces to improve osseointegration. Plasma nitriding treatments generate surfaces that favor osteoblast differentiation, a key event to the process of osteogenesis. Based on this, it is possible to hypothesize that plasma-nitrided Ti implants may positively impact osseointegration. Objective The aim of this study was to evaluate the in vivo bone response to Ti surfaces modified by plasma-nitriding treatments. Material and Methods Surface treatments consisted of 20% N2 and 80% H2, 450°C and 1.5 mbar during 1 h for planar and 3 h for hollow cathode. Untreated surface was used as control. Ten implants of each surface were placed into rabbit tibiae and 6 weeks post-implantation they were harvested for histological and histomorphometric analyses. Results Bone formation was observed in contact with all implants without statistically significant differences among the evaluated surfaces in terms of bone-to-implant contact, bone area between threads, and bone area within the mirror area. Conclusion Our results indicate that plasma nitriding treatments generate Ti implants that induce similar bone response to the untreated ones. Thus, as these treatments improve the physico-chemical properties of Ti without affecting its biocompatibility, they could be combined with modifications that favor bone formation in order to develop new implant surfaces.

  6. Measurement of breast tissue composition with dual energy cone-beam computed tomography: A postmortem study

    Energy Technology Data Exchange (ETDEWEB)

    Ding Huanjun; Ducote, Justin L.; Molloi, Sabee [Department of Radiological Sciences, University of California, Irvine, California 92697 (United States)

    2013-06-15

    Purpose: To investigate the feasibility of a three-material compositional measurement of water, lipid, and protein content of breast tissue with dual kVp cone-beam computed tomography (CT) for diagnostic purposes. Methods: Simulations were performed on a flat panel-based computed tomography system with a dual kVp technique in order to guide the selection of experimental acquisition parameters. The expected errors induced by using the proposed calibration materials were also estimated by simulation. Twenty pairs of postmortem breast samples were imaged with a flat-panel based dual kVp cone-beam CT system, followed by image-based material decomposition using calibration data obtained from a three-material phantom consisting of water, vegetable oil, and polyoxymethylene plastic. The tissue samples were then chemically decomposed into their respective water, lipid, and protein contents after imaging to allow direct comparison with data from dual energy decomposition. Results: Guided by results from simulation, the beam energies for the dual kVp cone-beam CT system were selected to be 50 and 120 kVp with the mean glandular dose divided equally between each exposure. The simulation also suggested that the use of polyoxymethylene as the calibration material for the measurement of pure protein may introduce an error of -11.0%. However, the tissue decomposition experiments, which employed a calibration phantom made out of water, oil, and polyoxymethylene, exhibited strong correlation with data from the chemical analysis. The average root-mean-square percentage error for water, lipid, and protein contents was 3.58% as compared with chemical analysis. Conclusions: The results of this study suggest that the water, lipid, and protein contents can be accurately measured using dual kVp cone-beam CT. The tissue compositional information may improve the sensitivity and specificity for breast cancer diagnosis.

  7. The effect of artificial gravity on plasma and tissue lipids in rats: The Cosmos 936 experiment

    Science.gov (United States)

    Ahlers, I.; Praslička, M.; Tigranyan, R. A.

    Plasma and tissue lipids in male SPF Wistar rats flown for 18.5 days aboard the Cosmos 936 biosatellite were analyzed. One group of rats was subjected to artificial gravity by use of a centrifuge during the flight. An experiment simulating known space flight factors other than weightlessness was done on Earth. An increase of total cholesterol in plasma, of nonesterified fatty acids in plasma and brown adipose tissue, of triacylglycerols in plasma, liver, thymus and bone marrow was noted several hours after biosatellite landing. Smaller changes were observed in the terrestrial control experiment. With the exception of triacylglycerol accumulation in bone marrow, these increases disappeared 25 days after biosatellite landing. Exposing the rats aboard the biosatellite to artificial gravity was beneficial in the sense that such exposure inhibited the phospholipid and triacylglycerol increase in plasma and inhibited the increase of triacylglycerol in liver and especially in bone marrow.

  8. Interleukin-18 in plasma and adipose tissue: effects of obesity, insulin resistance, and weight loss

    DEFF Research Database (Denmark)

    Bruun, Jens M; Stallknecht, Bente; Helge, Jørn W

    2007-01-01

    OBJECTIVE: Interleukin (IL)-18 is associated with obesity, insulin resistance, and cardiovascular disease. The present study compared 1) IL-18 in adipocytes versus stromal vascular (SV) cells, 2) IL-18 in plasma and adipose tissue (AT) in obese versus lean subjects, and 3) IL-18 in plasma, AT......, and skeletal muscle (SM) in obese subjects after weight loss. SUBJECTS AND METHODS: At baseline, plasma and AT IL-18 in 23 obese subjects were compared with that in 12 lean subjects. The obese subjects were submitted to a 15-week life-style intervention (hypocaloric diet and daily exercise) after which plasma...

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

    Directory of Open Access Journals (Sweden)

    Härkönen Pirkko

    2006-10-01

    Full Text Available Abstract Background Human breast tissue undergoes phases of proliferation, differentiation and regression regulated by changes of the levels of circulating sex hormones during the menstrual cycle or aging. Ovarian hormones also likely play a key role in the etiology and biology of breast cancer. Reports concerning the proliferative effects of steroid hormones on the normal epithelium of human breast have been conflicting. Some studies have shown that steroid hormones may predispose breast epithelial cells to malignant changes by stimulating their proliferation, which is known to be regulated tightly by stromal cells. The aim of this study was to investigate the effects of 17β-estradiol and medroxyprogesterone acetate on proliferation, apoptosis, expression of differentiation markers and steroid hormone receptors in breast epithelium using an in vitro model of freshly isolated human breast tissue, in which a proper interaction of breast epithelium and stroma has been maintained. Methods Human breast tissues were obtained from women undergoing surgery for breast tumours. Peritumoral tissues were excised and explants were cultured for 3 weeks in medium supplemented with E2 or MPA or with E2+MPA. Endpoints included histopathological, histomorphometric and immunohistochemical assessment of the breast explants. Results Culture of breast explants for 14 or 21 days with steroid hormones increased proliferative activity and the thickness of acinar and ductal epithelium. E2-treatment led to hyperplastic epithelial morphology, MPA to hypersecretory single-layered epithelium and E2+MPA to multilayered but organised epithelium. The proliferative response to E2 in comparison to control (p was more pronounced than to MPA (p or E2+MPA (p at 7 and 14 days for Ki-67 and PCNA. E2 treatment also decreased the proportion of apoptotic cells after 7 (p and 14 (p days. In addition, the relative number of ERα, ERβ and PR positive epithelial cells was decreased by all

  10. Nevirapine, sodium concentration and HIV-1 RNA in breast milk and plasma among HIV-infected women receiving short-course antiretroviral prophylaxis

    DEFF Research Database (Denmark)

    Salado-Rasmussen, Kirsten; Theilgaard, Zahra Persson; Chiduo, Mercy G.

    2015-01-01

    Introduction Risk factors for breast milk transmission of HIV-1 from mother to child include high plasma and breast milk viral load, low maternal CD4 count and breast pathology such as mastitis. Objective To determine the impact of nevirapine and subclinical mastitis on HIV-1 RNA in maternal plasma...... and breast milk after intrapartum single-dose nevirapine combined with either 1-week tail of Combivir (zidovudine/lamivudine) or single-dose Truvada (tenofovir/emtricitabine). Methods Maternal plasma and bilateral breast milk samples were collected between April 2008 and April 2011 at 1, 4 and 6 weeks...... postpartum from HIV-infected Tanzanian women. Moreover, plasma samples were collected at delivery from mother and infant. Results HIV-1 RNA was quantified in 1,212 breast milk samples from 273 women. At delivery, 96% of the women and 99% of the infants had detectable nevirapine in plasma with a median...

  11. Prognostic value of plasma levels of HIF-1a and PGC-1a in breast cancer.

    Science.gov (United States)

    Cai, Feng-Feng; Xu, Cheng; Pan, Xin; Cai, Lu; Lin, Xiao-Yan; Chen, Su; Biskup, Ewelina

    2016-11-22

    Cellular adaptive mechanisms are crucial for tumorigenesis and a common feature in solid tumor progression. Hypoxia-inducible factor-1α (HIF-1α) facilitates the biological response to hypoxia, advancing angiogenesis and metastatic potential of the tumor. The peroxisome proliferator-activated receptor γ coactivators 1α (PGC-1α) enhances mitochondrial biogenesis, favored by migratory/invasive cancer cells. We conducted a prospective, long-term follow up study to determine whether HIF-1α and PGC-1α can be implemented as predictive biomarker in breast cancer. HIF-1α and PGC-1α plasma concentrations were measured in patients and in healthy controls by enzyme linked immune sorbent assay. Breast cancer patients had significantly higher HIF-1α and PGC-1α levels, which correlated with clinicopathological features, overall with more aggressive cancer characteristics. Disease free and overall survival of breast cancer patients with high HIF-1α and PGC-1α were significantly poorer than in patients with low plasma levels. In multivariate analysis, high amount of PGC-1α showed independent prognostic value. Our data suggests that HIF-1α and PGC-1α may be promising, noninvasive, biomarkers with a high potential for future clinical implication to identify subgroups of patients with poorer prognosis and to indicate early, subclinical metastasis.

  12. Gene expression variation between distinct areas of breast cancer measured from paraffin-embedded tissue cores

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    Gugger Mathias

    2008-11-01

    Full Text Available Abstract Background Diagnosis and prognosis in breast cancer are mainly based on histology and immunohistochemistry of formalin-fixed, paraffin-embedded (FFPE material. Recently, gene expression analysis was shown to elucidate the biological variance between tumors and molecular markers were identified that led to new classification systems that provided better prognostic and predictive parameters. Archived FFPE samples represent an ideal source of tissue for translational research, as millions of tissue blocks exist from routine diagnostics and from clinical studies. These should be exploited to provide clinicians with more accurate prognostic and predictive information. Unfortunately, RNA derived from FFPE material is partially degraded and chemically modified and reliable gene expression measurement has only become successful after implementing novel and optimized procedures for RNA isolation, demodification and detection. Methods In this study we used tissue cylinders as known from the construction of tissue microarrays. RNA was isolated with a robust protocol recently developed for RNA derived from FFPE material. Gene expression was measured by quantitative reverse transcription PCR. Results Sixteen tissue blocks from 7 patients diagnosed with multiple histological subtypes of breast cancer were available for this study. After verification of appropriate localization, sufficient RNA yield and quality, 30 tissue cores were available for gene expression measurement on TaqMan® Low Density Arrays (16 invasive ductal carcinoma (IDC, 8 ductal carcinoma in situ (DCIS and 6 normal tissue, and 14 tissue cores were lost. Gene expression values were used to calculate scores representing the proliferation status (PRO, the estrogen receptor status and the HER2 status. The PRO scores measured from entire sections were similar to PRO scores determined from IDC tissue cores. Scores determined from normal tissue cores consistently revealed lower PRO scores

  13. Differentiating the two main histologic categories of fibroadenoma tissue from normal breast tissue by using multiphoton microscopy.

    Science.gov (United States)

    Nie, Y T; Wu, Y; Fu, F M; Lian, Y E; Zhuo, S M; Wang, C; Chen, J X

    2015-04-01

    Multiphoton microscopy has become a novel biological imaging technique that allows cellular and subcellular microstructure imaging based on two-photon excited fluorescence and second harmonic generation. In this work, we used multiphoton microscopy to obtain the high-contrast images of human normal breast tissue and two main histologic types of fibroadenoma (intracanalicular, pericanalicular). Moreover, quantitative image analysis was performed to characterize the changes of collagen morphology (collagen content, collagen orientation). The results show that multiphoton microscopy combined with quantitative method has the ability to identify the characteristics of fibroadenoma including changes of the duct architecture and collagen morphology in stroma. With the advancement of multiphoton microscopy, we believe that the technique has great potential to be a real-time histopathological diagnostic tool for intraoperative detection of fibroadenoma in the future.

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

    Science.gov (United States)

    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

  15. The Proliferative Activity of Mammary Epithelial Cells in Normal Tissue Predicts Breast Cancer Risk in Premenopausal Women.

    Science.gov (United States)

    Huh, Sung Jin; Oh, Hannah; Peterson, Michael A; Almendro, Vanessa; Hu, Rong; Bowden, Michaela; Lis, Rosina L; Cotter, Maura B; Loda, Massimo; Barry, William T; Polyak, Kornelia; Tamimi, Rulla M

    2016-04-01

    The frequency and proliferative activity of tissue-specific stem and progenitor cells are suggested to correlate with cancer risk. In this study, we investigated the association between breast cancer risk and the frequency of mammary epithelial cells expressing p27, estrogen receptor (ER), and Ki67 in normal breast tissue. We performed a nested case-control study of 302 women (69 breast cancer cases, 233 controls) who had been initially diagnosed with benign breast disease according to the Nurses' Health Studies. Immunofluorescence for p27, ER, and Ki67 was performed on tissue microarrays constructed from benign biopsies containing normal mammary epithelium and scored by computational image analysis. We found that the frequency of Ki67(+) cells was positively associated with breast cancer risk among premenopausal women [OR = 10.1, 95% confidence interval (CI) = 2.12-48.0]. Conversely, the frequency of ER(+) or p27(+) cells was inversely, but not significantly, associated with subsequent breast cancer risk (ER(+): OR = 0.70, 95% CI, 0.33-1.50; p27(+): OR = 0.89, 95% CI, 0.45-1.75). Notably, high Ki67(+)/low p27(+) and high Ki67(+)/low ER(+) cell frequencies were significantly associated with a 5-fold higher risk of breast cancer compared with low Ki67(+)/low p27(+) and low Ki67(+)/low ER(+) cell frequencies, respectively, among premenopausal women (Ki67(hi)/p27(lo): OR = 5.08, 95% CI, 1.43-18.1; Ki67(hi)/ER(lo): OR = 4.68, 95% CI, 1.63-13.5). Taken together, our data suggest that the fraction of actively cycling cells in normal breast tissue may represent a marker for breast cancer risk assessment, which may therefore impact the frequency of screening procedures in at-risk women. Cancer Res; 76(7); 1926-34. ©2016 AACR.

  16. Comparison of breast cancer to healthy control tissue discovers novel markers with potential for prognosis and early detection.

    Science.gov (United States)

    Schummer, Michèl; Green, Ann; Beatty, J David; Karlan, Beth Y; Karlan, Scott; Gross, Jenny; Thornton, Sean; McIntosh, Martin; Urban, Nicole

    2010-02-09

    This study was initiated to identify biomarkers with potential value for the early detection of poor-outcome breast cancer. Two sets of well-characterized tissues were utilized: one from breast cancer patients with favorable vs. poor outcome and the other from healthy women undergoing reduction mammaplasty. Over 46 differentially expressed genes were identified from a large list of potential targets by a) mining publicly available expression data (identifying 134 genes for quantitative PCR) and b) utilizing a commercial PCR array. Three genes show elevated expression in cancers with poor outcome and low expression in all other tissues, warranting further investigation as potential blood markers for early detection of cancers with poor outcome. Twelve genes showed lower expression in cancers with poor outcome than in cancers with favorable outcome but no differential expression between aggressive cancers and most healthy controls. These genes are more likely to be useful as prognostic tissue markers than as serum markers for early detection of aggressive disease. As a secondary finding was that, when histologically normal breast tissue was removed from a distant site in a breast with cancer, 7 of 38 specimens displayed a cancer-like expression profile, while the remaining 31 were genetically similar to the reduction mammaplasty control group. This finding suggests that some regions of ipsilateral histologically 'normal' breast tissue are predisposed to becoming malignant and that normal-appearing tissue with malignant signature might warrant treatment to prevent new primary tumors.

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

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    Issac Niwas Swamidoss

    2013-01-01

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

  18. Immunoexpression of the relaxin receptor LGR7 in breast and uterine tissues of humans and primates

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    Milde-Langosch Karin

    2003-11-01

    Full Text Available Abstract Background The receptor for the peptide hormone relaxin has recently been identified as the heptahelical G-protein coupled receptor, LGR7. In order to generate molecular tools with which to characterize both in vivo and in vitro expression of this receptor in human and primate tissues, specific monotypic antibodies have been generated and applied to a preliminary analysis of human and primate female reproductive tissues. Methods Three peptide sequences were identified from the proposed open reading frame of the cloned LGR7 receptor gene, representing both extracellular and intracellular domains. Two to three rabbits were immunized for each epitope, and the resulting sera subjected to a systematic validation using cultured cells transiently transfected with a receptor-expressing gene construct, or appropriate control constructs. Results Human and monkey (marmoset, macaque endometrium showed consistent and specific immunostaining in the stromal cells close to glands. Staining appeared to be more intense in the luteal phase of the cycle. Weak immunostaining was also evident in the endometrial epithelial cells of the marmoset. A myoma in one patient exhibited strong immunostaining in the circumscribing connective tissue. Uterine expression was supported by RT-PCR results from cultured primary endometrial and myometrial cells. Human breast tissue (healthy and tumors consistently indicated specific immunostaining in the interstitial connective (stromal tissue within the glands, but not in epithelial or myoepithelial cells, except in some tumors, where a few epithelial and tumor cells also showed weak epitope expression. Conclusions Using validated monotypic antibodies recognizing different epitopes of the LGR7 receptor, and from different immunized animals, and in different primate species, a consistent pattern of LGR7 expression was observed in the stromal (connective tissue cells of the endometrium and breast, consistent also with the known

  19. Selective photothermal interaction using near-infrared laser and laser-absorbing dye in gel phantom and chicken breast tissue

    Science.gov (United States)

    Cowan, Thomas M.; Liu, Guangyu; Simmons, Sarah; Real, Jeremy; Lucroy, Michael D.; Bartels, Kenneth E.; Nordquist, Robert E.; Chen, Wei R.

    2002-06-01

    Photothermal interaction of an 805-nm diode laser with an absorptive dye, indocyanine green (ICG), has been shown to be an efficacious therapy for metastatic breast tumors in a rat model when combined with immunoadjuvant. When ICG solution was injected into the target tissue, selective tissue destruction can be achieved. To study the selective photothermal interaction, temperature change in irradiated tissue was achieved. To study the selective photothermal interaction, temperature change in irradiated tissue was studied using chicken breast tissue and phantom composed of gelatin and intralipid. ICG solution was mixed with gel phantom to simulate dye-enhanced target tissue. The target gel was then embedded in chicken breast tissue. The temperature change of irradiated chicken and gel phantom was measured by needle temperature probes at different tissue depths and radii from the center of the laser beam to construct a two-dimensional array of temperature change in a cylindrical coordinate system. It was shown that it is possible to selectively raise the temperature of deep target tissue while not substantially heating nontargeted tissue. A Nd:YAG laser was also used to irradiate the tissue-gel system and the photothermal results were compared with that using the 805-nm laser.

  20. The association between breast tissue optical content and mammographic density in pre- and post-menopausal women.

    Directory of Open Access Journals (Sweden)

    Kristina M Blackmore

    Full Text Available Mammographic density (MD, associated with higher water and lower fat content in the breast, is strongly related to breast cancer risk. Optical attenuation spectroscopy (OS is a non-imaging method of evaluating breast tissue composition by red and near-infrared light transmitted through the breast that, unlike mammography, does not involve radiation. OS provides information on wavelength dependent light scattering of tissue and on absorption by water, lipid, oxy-, deoxy-hemoglobin. We propose that OS could be an alternative marker of breast cancer risk and that OS breast tissue measures will be associated with MD. In the present analysis, we developed an algorithm to estimate breast tissue composition and light scattering parameters using a spectrally constrained global fitting procedure employing a diffuse light transport model. OS measurements were obtained from 202 pre- and post-menopausal women with normal mammograms. Percent density (PD and dense area (DA were measured using Cumulus. The association between OS tissue composition and PD and DA was analyzed using linear regression adjusted for body mass index. Among pre-menopausal women, lipid content was significantly inversely associated with square root transformed PD (β = -0.05, p = 0.0002 and DA (β = -0.05, p = 0.019; water content was significantly positively associated with PD (β = 0.06, p = 0.008. Tissue oxygen saturation was marginally inversely associated with PD (β = -0.03, p = 0.057 but significantly inversely associated with DA (β = -0.10, p = 0.002. Among post-menopausal women lipid and water content were significantly associated (negatively and positively, respectively with PD (β lipid = -0.08, β water = 0.14, both p<0.0001 and DA (β lipid = -0.10, p<0.0001; β water = 0.11, p = 0.001. The association between OS breast content and PD and DA is consistent with more proliferation in dense tissue of younger women, greater lipid content in low density tissue and higher water

  1. Breast augmentation surgery

    Science.gov (United States)

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

  2. Plasma tissue inhibitor of metalloproteinases-1 as a biological marker?

    DEFF Research Database (Denmark)

    Lomholt, Anne F.; Frederiksen, Camilla B.; Christensen, Ib J.;

    2007-01-01

    Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) may be a valuable biological marker in Colorectal Cancer (CRC). However, prospective validation of TIMP-1 as a biological marker should include a series of pre-analytical considerations. TIMP-1 is stored in platelets, which may degranulate during ...

  3. Atmospheric pressure plasma jets interacting with liquid covered tissue: touching and not-touching the liquid

    Science.gov (United States)

    Norberg, Seth A.; Tian, Wei; Johnsen, Eric; Kushner, Mark J.

    2014-11-01

    In the use of atmospheric pressure plasma jets in biological applications, the plasma-produced charged and neutral species in the plume of the jet often interact with a thin layer of liquid covering the tissue being treated. The plasma-produced reactivity must then penetrate through the liquid layer to reach the tissue. In this computational investigation, a plasma jet created by a single discharge pulse at three different voltages was directed onto a 200 µm water layer covering tissue followed by a 10 s afterglow. The magnitude of the voltage and its pulse length determined if the ionization wave producing the plasma plume reached the surface of the liquid. When the ionization wave touches the surface, significantly more charged species were created in the water layer with H3O+aq, O3-aq, and O2-aq being the dominant terminal species. More aqueous OHaq, H2O2aq, and O3aq were also formed when the plasma plume touches the surface. The single pulse examined here corresponds to a low repetition rate plasma jet where reactive species would be blown out of the volume between pulses and there is not recirculation of flow or turbulence. For these conditions, NxOy species do not accumulate in the volume. As a result, aqueous nitrites, nitrates, and peroxynitrite, and the HNO3aq and HOONOaq, which trace their origin to solvated NxOy, have low densities.

  4. Differential Gene Expression of BRCA1,ERBB2 and TP53 biomarkers between Human Breast Tissue and Peripheral Blood Samples of Breast Cancer.

    Science.gov (United States)

    Zghair, Abdulrazzaq Neamah; Sinha, Deepak Kumar; Kassim, Arkan; Alfaham, Mohmmad; Sharma, Anil K

    2016-01-01

    Breast cancer is a most common malignancy especially in Iraqi women accounting for high morbidity and mortality. Mutations in BRCA1 gene is one of the important genetic predisposing factors inbreast cancer. Similarly ERBB2 and TP53 are also key prognostic markers in breast cancer treatment.We were interested to explore the gene expression profiles of BRCA1, ERBB2 and TP53 in breast cancer women patients from Iraq so as to assess the potential of such markers in breast cancer treatment. The mRNA levels were significantly over-expressed in tumor tissues in comparison to normal ones with p values (pTP53 and benign tissue samples as well. However in blood samples, no considerable expression of these markers was observed. Out of three selected genes, ERBB2 expression was significantly expressed in comparison to BRCA1 and TP53 in cancer tissue. Mutation analysis of BRCA1, ERBB2 and TP53 has been made to find out the region most susceptible to mutations in these genes The BRCA1 exon 11, ERBB2 16 and TP53 exon 5 displayed increased chances of having mutations. We can conclude from the study that differential gene expression of BRCA1, ERBB2 and TP53 at mRNA levels may act as a diagnostic marker of circulating tumor cells having important prognostic value in breast cancer patients.

  5. Breast Reconstruction with Flap Surgery

    Science.gov (United States)

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

  6. Measurement of the hyperelastic properties of 44 pathological ex vivo breast tissue samples

    Science.gov (United States)

    O'Hagan, Joseph J.; Samani, Abbas

    2009-04-01

    The elastic and hyperelastic properties of biological soft tissues have been of interest to the medical community. There are several biomedical applications where parameters characterizing such properties are critical for a reliable clinical outcome. These applications include surgery planning, needle biopsy and brachtherapy where tissue biomechanical modeling is involved. Another important application is interpreting nonlinear elastography images. While there has been considerable research on the measurement of the linear elastic modulus of small tissue samples, little research has been conducted for measuring parameters that characterize the nonlinear elasticity of tissues included in tissue slice specimens. This work presents hyperelastic measurement results of 44 pathological ex vivo breast tissue samples. For each sample, five hyperelastic models have been used, including the Yeoh, N = 2 polynomial, N = 1 Ogden, Arruda-Boyce, and Veronda-Westmann models. Results show that the Yeoh, polynomial and Ogden models are the most accurate in terms of fitting experimental data. The results indicate that almost all of the parameters corresponding to the pathological tissues are between two times to over two orders of magnitude larger than those of normal tissues, with C11 showing the most significant difference. Furthermore, statistical analysis indicates that C02 of the Yeoh model, and C11 and C20 of the polynomial model have very good potential for cancer classification as they show statistically significant differences for various cancer types, especially for invasive lobular carcinoma. In addition to the potential for use in cancer classification, the presented data are very important for applications such as surgery planning and virtual reality based clinician training systems where accurate nonlinear tissue response modeling is required.

  7. Assessment of Breast, Brain and Skin Pathological Tissue Using Full Field OCM

    Science.gov (United States)

    Dalimier, Eugénie; Assayag, Osnath; Harms, Fabrice; Boccara, A. Claude

    The aim of this chapter is to assess whether the images of the breast, brain, and skin tissue obtained by FFOCM contain sufficient detail to allow pathologists to make a diagnosis of cancer and other pathologies comparable to what was obtained by conventional histological techniques. More precisely, it is necessary to verify on FFOCM images if it is possible to differentiate a healthy area from a pathological area. The reader interested in other organs or in animal studies may find a large number of 2D or 3D images in the atlas [2].

  8. Polarity determination in breast tissue: Desmosomal adhesion, myoepit helial cells, and laminin 1

    Energy Technology Data Exchange (ETDEWEB)

    Bissell, Mina J.; Bilder, David

    2003-06-05

    In all epithelial organs, apicobasal polarity determines functional integrity and contributes to the maintenance of tissue and organ specificity. In the breast, the functional unit is a polar double-layered tube consisting of luminal epithelial cells surrounded by myoepithelial cells and a basement membrane. It is far from clear how this double-layered structure is established and how polarity is maintained. Two recent papers have shed some light onto this intriguing problem in mammary gland biology. The results point to desmosomes and laminin 1 as having crucial roles. However, some questions remain.

  9. The evaluation of breast tissues removed during reductive mammaplasty with dual energy X-ray absorptiometry

    Energy Technology Data Exchange (ETDEWEB)

    De Lorenzo, Antonino [Division of Human Nutrition, University of Tor Vergata in Rome (Italy); Gravante, Gianpiero [Division of Human Nutrition, University of Tor Vergata in Rome (Italy); Department of Surgery, Whipps Cross University Hospital, London (United Kingdom)], E-mail: ggravante@hotmail.com; Sorge, Roberto [Laboratory of Biometry, University of Tor Vergata in Rome (Italy); Nicoli, Fabio; Caruso, Riccardo; Araco, Antonino [Department of Plastic Surgery, University of Tor Vergata in Rome (Italy); Servidio, Michele [Division of Human Nutrition, University of Tor Vergata in Rome (Italy); Orlandi, Augusto [Department of Biopathology, Anatomic Pathology Institute, University of Tor Vergata in Rome (Italy); Cervelli, Valerio [Department of Plastic Surgery, University of Tor Vergata in Rome (Italy)

    2009-06-15

    Purpose: We conducted a case-control study in which patients were evaluated with dual energy X-ray absorptiometry (DEXA) before and after breast reduction surgery, and results were correlated with the histological examination. Our goal was to confirm the DEXA as a precise technique for the measurement of breast composition, in order to propose it for the preoperative evaluation of plastic surgery patients. Materials and methods: We prospectively recruited all women that underwent reduction mammaplasty and excluded patients with contraindications to the operation or those that previously underwent bariatric surgery to reduce their weight. Patients were evaluated with DEXA 1 week before and after surgery. Results: From February to October 2006 we recruited 25 patients. The statistical analysis found a significant reduction of weight, BMI, regional fat free mass and fat mass after the operation. The comparison between DEXA and the histological analysis produced a correlation r = 0.989 (r{sup 2} = 0.978), with a predictivity of 98% and a percentage of error 8.3% (95% confidence intervals -252.6, 273.7; 95% limits of agreements of Bland and Altman -436.0, 457.1). Similar results were obtained with the analysis of fat. Conclusions: Our study demonstrated that conventional segmental DEXA is a very precise technique to measure the amount of tissue removed in breast reductions and could open future application in the preoperative assessment of patients undergoing such operations.

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

    Science.gov (United States)

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

    2010-12-01

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

  11. Variation of autosomes and X chromosome STR in breast cancer and gynecological cancer tissues

    Directory of Open Access Journals (Sweden)

    Hou Youxiang

    2017-04-01

    Full Text Available This study analyses 1000 cases of patients with breast cancer and 2000 cases of patients with gynecological cancer (1000 cases of malignant tumor, 1000 cases of benign tumors, where breast cancer and malignant tumor patients comprise the observation group, while patients with benign tumors comprise the control group. Through DNA extraction, STR genotyping and variation verification, microdissection, individual STR mutation rate and loci STR mutation rate of the two groups of patients were calculated. Results show that there are no significant (P > 0.05 differences in the STR variation of autosomes and X chromosome between patients in the observation group and those in the reference group. However, significant (P < 0.05 intergroup differences were found for STR variation typing between patients with malignant and benign tumors. Using STR genotyping for autosomes and X chromosomes, gynecological cancer patients were found to be more likely to mutate, with a clear relationship between STR variation and tumor differentiation degrees. The study on the variation analysis of autosomes and X chromosome STR in breast and gynecological cancer tissues is expected to have a high application value when applied to medical research and identification processes.

  12. The impact of bilateral salpingo-oophorectomy on breast MRI background parenchymal enhancement and fibroglandular tissue

    Energy Technology Data Exchange (ETDEWEB)

    Price, E.R. [University of California, San Francisco, Department of Radiology and Biomedical Imaging, Division of Women' s Imaging, San Francisco, California (United States); Brooks, J.D. [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Watson, E.J.; Brennan, S.B.; Morris, E.A. [Department of Radiology, Breast Imaging Section, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Comen, E.A. [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    2014-01-15

    The objective of this study was to evaluate the effect of bilateral salpingo-oophorectomy (BSO) on background parenchymal enhancement (BPE) and the amount of fibroglandular tissue (FGT) seen on breast MRI. Retrospective review identified 21 BRCA mutation carriers who underwent breast MRI before and after elective BSO. After exclusion of patients placed on postoperative hormone replacement therapy, there were 18 eligible patients. Blinded to surgical status, three independent readers used categorical scales to rate BPE (minimal, mild, moderate, marked) and the amount of FGT (fatty, scattered, heterogeneously dense, dense) on pre- and post-BSO MRI examinations. The sign test was used to assess for changes in the categorical ratings of BPE and FGT. Significant proportions of women demonstrated decreases in BPE and in the amount of FGT following oophorectomy (P = 0.004 and 0.02, respectively.) BPE decreases were larger and seen earlier than FGT changes. There was no significant relationship between age/body mass index and changes in BPE and FGT. BPE and the amount of FGT seen on breast MRI are significantly decreased by oophorectomy; BPE decreases to a greater extent and earlier than FGT. (orig.)

  13. Tissue to plasma capillary permeability of 131I-albumin in the perfused rabbit ear

    DEFF Research Database (Denmark)

    Bent-Hansen, L; Svendsen, Jesper Hastrup

    1991-01-01

    The tissue to plasma transfer of 131I-albumin was recorded in perfused rabbit ears (n = 6) following equilibration for 24 hr. 125I-fibrinogen served as the plasma marker, and was introduced intravenously 15 min before clamping. The ears were rollerpump perfused with isotonic diluted plasma...... at a constant rate of (mean +/- SD) 5.1 +/- 1.5 ml (min.100 g)-1. The mean extravascular albumin distribution volume was 12.4 +/- 1.1 ml.100 g-1, and the fibrinogen volume (plasma volume in tissue) was 3.1 +/- 0.4 ml.100 g-1 as determined from biopsies of the contralateral ear. The initial transfer of albumin...

  14. High‐throughput automated scoring of Ki67 in breast cancer tissue microarrays from the Breast Cancer Association Consortium

    Science.gov (United States)

    Howat, William J; Daley, Frances; Zabaglo, Lila; McDuffus, Leigh‐Anne; Blows, Fiona; Coulson, Penny; Raza Ali, H; Benitez, Javier; Milne, Roger; Brenner, Herman; Stegmaier, Christa; Mannermaa, Arto; Chang‐Claude, Jenny; Rudolph, Anja; Sinn, Peter; Couch, Fergus J; Tollenaar, Rob A.E.M.; Devilee, Peter; Figueroa, Jonine; Sherman, Mark E; Lissowska, Jolanta; Hewitt, Stephen; Eccles, Diana; Hooning, Maartje J; Hollestelle, Antoinette; WM Martens, John; HM van Deurzen, Carolien; Investigators, kConFab; Bolla, Manjeet K; Wang, Qin; Jones, Michael; Schoemaker, Minouk; Broeks, Annegien; van Leeuwen, Flora E; Van't Veer, Laura; Swerdlow, Anthony J; Orr, Nick; Dowsett, Mitch; Easton, Douglas; Schmidt, Marjanka K; Pharoah, Paul D; Garcia‐Closas, Montserrat

    2016-01-01

    Abstract Automated methods are needed to facilitate high‐throughput and reproducible scoring of Ki67 and other markers in breast cancer tissue microarrays (TMAs) in large‐scale studies. To address this need, we developed an automated protocol for Ki67 scoring and evaluated its performance in studies from the Breast Cancer Association Consortium. We utilized 166 TMAs containing 16,953 tumour cores representing 9,059 breast cancer cases, from 13 studies, with information on other clinical and pathological characteristics. TMAs were stained for Ki67 using standard immunohistochemical procedures, and scanned and digitized using the Ariol system. An automated algorithm was developed for the scoring of Ki67, and scores were compared to computer assisted visual (CAV) scores in a subset of 15 TMAs in a training set. We also assessed the correlation between automated Ki67 scores and other clinical and pathological characteristics. Overall, we observed good discriminatory accuracy (AUC = 85%) and good agreement (kappa = 0.64) between the automated and CAV scoring methods in the training set. The performance of the automated method varied by TMA (kappa range= 0.37–0.87) and study (kappa range = 0.39–0.69). The automated method performed better in satisfactory cores (kappa = 0.68) than suboptimal (kappa = 0.51) cores (p‐value for comparison = 0.005); and among cores with higher total nuclei counted by the machine (4,000–4,500 cells: kappa = 0.78) than those with lower counts (50–500 cells: kappa = 0.41; p‐value = 0.010). Among the 9,059 cases in this study, the correlations between automated Ki67 and clinical and pathological characteristics were found to be in the expected directions. Our findings indicate that automated scoring of Ki67 can be an efficient method to obtain good quality data across large numbers of TMAs from multicentre studies. However, robust algorithm development and rigorous pre‐ and post

  15. Validation of coded aperture coherent scatter spectral imaging for normal and neoplastic breast tissues via surgical pathology

    Science.gov (United States)

    Morris, R. E.; Albanese, K. E.; Lakshmanan, M. N.; McCall, S. J.; Greenberg, J. A.; Kapadia, A. J.

    2016-03-01

    This study intends to validate the sensitivity and specificity of coded aperture coherent scatter spectral imaging (CACSSI) by comparison to standard histological preparation and pathologic analysis methods used to differentiate normal and neoplastic breast tissues. A composite overlay of the CACSSI rendered image and pathologist interpreted stained sections validate the ability of CACSSI to differentiate normal and neoplastic breast structures ex-vivo. Via comparison to pathologist annotated slides, the CACSSI system may be further optimized to maximize sensitivity and specificity for differentiation of breast carcinomas.

  16. Tissue antioxidants and postmenopausal breast cancer : the European Community Multicentre Study on Antioxidants, Myocardial Infarction and Cancer of the Breast (EURAMIC)

    NARCIS (Netherlands)

    Veer, P. van 't; Strain, J.J.; Fernandez-Crehuet, J.; Martin, B.C.; Thamm, M.; Kardinaal, A.F.M.; Kohlmeier, L.; Huttunen, J.K.; Martin-Moreno, J.M.; Kok, F.J.

    1996-01-01

    Antioxidants may protect against free radical mediated carcinogenesis. Epidemiological studies have not confirmed this hypothesis for breast cancer, possibly because of methodological limitations. Time-integrated exposure of α-tocopherol and β-carotene in adipose tissue, and selenium in toenails was

  17. [Plasma and tissue lipids in rats after a flight on the Kosmos-1129 biosatellite].

    Science.gov (United States)

    Ahlers, J; Tigranian, R A; D'jatelinka, J; Smajda, B; Toropila, M

    1982-01-01

    Concentrations of triglycerides, total cholesterol, lipid phosphorus and nonesterified fatty acids were measured in blood plasma, liver, thymus, bone marrow and adipose tissues of rats flown for 18.5 days onboard the biosatellite Cosmos-1129. This exposure was accompanied by increases in lipomobilization, content of total cholesterol and lipid phosphorus in plasma, and triglycerides in the thymus and bone marrow. The postflight exposure to repeated stresses demonstrated changes in the lipid content in all animal groups, especially in flight rats.

  18. Plasma and tissue pharmacokinetics of marbofloxacin in experimentally infected chickens with Mycoplasma gallisepticum and Escherichia coli.

    Science.gov (United States)

    Ding, H; Wang, L; Shen, X; Gu, X; Zeng, D; Zeng, Z

    2013-10-01

    The plasma and tissue pharmacokinetics of marbofloxacin in chickens experimentally infected with Mycoplasma gallisepticum and Escherichia coli were studied. Marbofloxacin was given to 66 infected chickens by oral administration at a dosage of 5 mg/kg b.w., once a day for three days. Plasma, brain, kidney, liver, lung, muscle and trachea were collected and marbofloxacin concentrations were analyzed by a high performance liquid chromatography method. In the infected chickens, maximal marbofloxacin concentrations in plasma, brain, kidney, liver, lung, muscle and trachea were 1.84, 1.33, 7.35, 5.61, 3.12, 2.98, and 4.51 g/mL (g); the elimination half-lives of marbofloxacin were 6.8, 2.74, 9.31, 8.45, 9.55, 11.53 and 5.46 h for plasma, brain, kidney, liver, lung, muscle and trachea, respectively. AUC were calculated to be 9.68, 8.04, 45.1, 27.03, 20.56, 19.47, and 32.68 μg/mL (g) for plasma, brain, kidney, liver, lung, muscle and trachea, respectively. Marbofloxacin concentration in tissues except for brain exceeded marbofloxacin concentration in plasma, with AUC(tissue) /AUC(plasma) ranging from 2.01 to 4.66 and Peak(tissue) /Peak(plasma) ranging from 1.62 to 3.99. The results showed that a marbofloxacin dosage of 5 mg/kg administered orally at 24 h intervals may provide successful treatment of chicken with MG and E. coli infection.

  19. Oral administration of lithium increases tissue magnesium contents but not plasma magnesium level in rats.

    Science.gov (United States)

    Kiełczykowska, Małgorzata; Musik, Irena; Hordyjewska, Anna; Boguszewska, Anna; Lewandowska, Anna; Pasternak, Kazimierz

    2007-01-01

    The aim of this work was to determine the influence of different doses of lithium on magnesium concentration in plasma and tissues of rats. For a period of eight weeks rats had been provided with aqueous solutions of Li(2)CO(3) whose concentrations were established as follows: 0.7; 1.4; 2.6; 3.6; 7.1; 10.7 mmol Li(+)/l. Magnesium concentration was determined in plasma and tissue supernatants. Lithium caused no changes in magnesium concentration in plasma, whereas Mg concentration in tissues was found to be enhanced, although the degree of the increment depended on the studied tissue. In the liver, brain and heart muscle, the increase was statistically insignificant vs. control. In the kidney, the higher Li doses were required to result in the significant Mg enhancement, whereas in femoral muscle all the used doses caused well-marked Mg increase vs. control. Positive correlations between average daily Li intake and tissue Mg concentration in the kidney (r = 0.650) and femoral muscle (r = 0.696) were found. In conclusion, the present study indicates that the different Li doses disturbed tissue homeostasis of magnesium. The increase in Mg tissue concentration, observed in groups receiving higher Li doses can influence nervous-muscular excitability.

  20. IGF1 genotype, mean plasma level and breast cancer risk in the Hawaii/Los Angeles multiethnic cohort.

    Science.gov (United States)

    DeLellis, K; Ingles, S; Kolonel, L; McKean-Cowdin, R; Henderson, B; Stanczyk, F; Probst-Hensch, N M

    2003-01-27

    The insulin-like growth factor 1 gene (IGF1) is a strong candidate gene for a breast cancer susceptibility model. We investigated a dinucleotide repeat 969 bp upstream from the transcription start site of the IGF1 gene for possible associations with plasma IGF1 levels and breast cancer risk in a multiethnic group of postmenopausal women. Furthermore, we investigated the relation between race/ethnicity, mean plasma IGF1 levels and breast cancer rates in the Hawaii/Los Angeles Multiethnic Cohort. The mean age-adjusted IGF1 level among Latino-American women, 116 ng ml(-1), was statistically significantly lower than the mean age-adjusted IGF1 levels for each of the three other racial/ethnic groups, African-American, Japanese-American and Non-Latino White women (146, 144 and 145 ng ml(-1), respectively) (PLatino-American women have the lowest breast cancer rates of any racial/ethnic group in the cohort. These results support the investigation of an expansion of the hypothesis for an important role of IGF1 in breast cancer tumorigenesis to different racial/ethnic groups and to postmenopausal women. It is unlikely that any involvement of IGF1 in breast cancer aetiology is mediated by the IGF1 dinucleotide repeat polymorphism, which was not significantly associated with circulating IGF1 levels nor breast cancer risk in this study. Research into relevant determinants of IGF1 levels in the blood must continue.

  1. Diagnosis of Breast Cancer Tissues Using 785 nm Miniature Raman Spectrometer and Pattern Regression

    Directory of Open Access Journals (Sweden)

    Qingbo Li

    2017-03-01

    Full Text Available For achieving the development of a portable, low-cost and in vivo cancer diagnosis instrument, a laser 785 nm miniature Raman spectrometer was used to acquire the Raman spectra for breast cancer detection in this paper. However, because of the low spectral signal-to-noise ratio, it is difficult to achieve high discrimination accuracy by using the miniature Raman spectrometer. Therefore, a pattern recognition method of the adaptive net analyte signal (NAS weight k-local hyperplane (ANWKH is proposed to increase the classification accuracy. ANWKH is an extension and improvement of K-local hyperplane distance nearest-neighbor (HKNN, and combines the advantages of the adaptive weight k-local hyperplane (AWKH and the net analyte signal (NAS. In this algorithm, NAS was first used to eliminate the influence caused by other non-target factors. Then, the distance between the test set samples and hyperplane was calculated with consideration of the feature weights. The HKNN only works well for small values of the nearest-neighbor. However, the accuracy decreases with increasing values of the nearest-neighbor. The method presented in this paper can resolve the basic shortcoming by using the feature weights. The original spectra are projected into the vertical subspace without the objective factors. NAS was employed to obtain the spectra without irrelevant information. NAS can improve the classification accuracy, sensitivity, and specificity of breast cancer early diagnosis. Experimental results of Raman spectra detection in vitro of breast tissues showed that the proposed algorithm can obtain high classification accuracy, sensitivity, and specificity. This paper demonstrates that the ANWKH algorithm is feasible for early clinical diagnosis of breast cancer in the future.

  2. Haploinsufficiency for BRCA1 is associated with normal levels of DNA nucleotide excision repair in breast tissue and blood lymphocytes

    Directory of Open Access Journals (Sweden)

    Johnson Jennifer M

    2005-06-01

    Full Text Available Abstract Background Screening mammography has had a positive impact on breast cancer mortality but cannot detect all breast tumors. In a small study, we confirmed that low power magnetic resonance imaging (MRI could identify mammographically undetectable tumors by applying it to a high risk population. Tumors detected by this new technology could have unique etiologies and/or presentations, and may represent an increasing proportion of clinical practice as new screening methods are validated and applied. A very important aspect of this etiology is genomic instability, which is associated with the loss of activity of the breast cancer-predisposing genes BRCA1 and BRCA2. In sporadic breast cancer, however, there is evidence for the involvement of a different pathway of DNA repair, nucleotide excision repair (NER, which remediates lesions that cause a distortion of the DNA helix, including DNA cross-links. Case presentation We describe a breast cancer patient with a mammographically undetectable stage I tumor identified in our MRI screening study. She was originally considered to be at high risk due to the familial occurrence of breast and other types of cancer, and after diagnosis was confirmed as a carrier of a Q1200X mutation in the BRCA1 gene. In vitro analysis of her normal breast tissue showed no differences in growth rate or differentiation potential from disease-free controls. Analysis of cultured blood lymphocyte and breast epithelial cell samples with the unscheduled DNA synthesis (UDS assay revealed no deficiency in NER. Conclusion As new breast cancer screening methods become available and cost effective, patients such as this one will constitute an increasing proportion of the incident population, so it is important to determine whether they differ from current patients in any clinically important ways. Despite her status as a BRCA1 mutation carrier, and her mammographically dense breast tissue, we did not find increased cell

  3. Arginine-deficient diets alter plasma and tissue amino acids in young and aged rats.

    Science.gov (United States)

    Gross, K L; Hartman, W J; Ronnenberg, A; Prior, R L

    1991-10-01

    Blood and urine metabolites were measured in two experiments for young (2-mo-old) and aged (20-mo-old) male Sprague-Dawley rats fed arginine-devoid diets made isonitrogenous to a control 1.12% arginine diet by adding alanine or glycine. Diet, fed for 7 or 13 d, had little effect on urinary or plasma ammonia and urea. Urinary orotate excretion was more than 40-fold higher in rats fed the arginine-deficient diets (P less than 0.01) in both experiments. Source of nonessential N (alanine or glycine) in the arginine-deficient diets did not alter orotic acid excretion or plasma or urine ammonia or urea. Changes in plasma arginine, alanine and glycine concentrations reflected the levels of these amino acids in the diet. Tissue ornithine levels reflected dietary arginine level, but tissue citrulline was unaffected by dietary arginine. Glutamate and glutamine were greater in the plasma and liver of rats fed arginine-deficient diets. Plasma concentrations of glutamate and glutamine were positively correlated with urinary orotic acid excretion (P less than 0.05) and ornithine and arginine were negatively correlated with orotic acid excretion (P less than 0.01). Increased tissue glutamine may be related to the greater orotate excretion in rats fed arginine-devoid diets. The metabolic responses to dietary arginine deficiency were similar in young and aged rats. In general, concentrations of amino acids in plasma, liver and spleen were higher in aged rats.

  4. An effective ultrasonic strain measurement-based shear modulus reconstruction technique for superficial tissues - demonstration on in vitro pork ribs and in vivo human breast tissues

    Science.gov (United States)

    Sumi, Chikayoshi; Nakayama, Kiyoshi; Kubota, Mitsuhiro

    2000-06-01

    An effective shear modulus reconstruction technique is described which uses ultrasonic strain measurements for diagnosis of superficial tissues, i.e. our previously developed ultrasonic strain measurement and shear modulus reconstruction methods are combined and enhanced. The technique realizes very low computational load, yet yields fairly high quantitativeness, high stability and spatial resolution, and large dynamic range. The suitability of the method is demonstrated on in vitro pork ribs and in vivo human breast tissues (fibroadenoma and scirrhous carcinoma).

  5. Mastectomy Weight and Tissue Expander Volume Predict Necrosis and Increased Costs Associated with Breast Reconstruction

    Science.gov (United States)

    Yalanis, Georgia C.; Nag, Shayoni; Georgek, Jakob R.; Cooney, Carisa M.; Manahan, Michele A.; Rosson, Gedge D.

    2015-01-01

    Introduction: Impaired vascular perfusion in tissue expander (TE) breast reconstruction leads to mastectomy skin necrosis. We investigated factors and costs associated with skin necrosis in postmastectomy breast reconstruction. Methods: Retrospective review of 169 women with immediate TE placement following mastectomy between May 1, 2009 and May 31, 2013 was performed. Patient demographics, comorbidities, intraoperative, and postoperative outcomes were collected. Logistic regression analysis on individual variables was performed to determine the effects of tissue expander fill volume and mastectomy specimen weight on skin necrosis. Billing data was obtained to determine the financial burden associated with necrosis. Results: This study included 253 breast reconstructions with immediate TE placement from 169 women. Skin necrosis occurred in 20 flaps for 15 patients (8.9%). Patients with hypertension had 8 times higher odds of skin necrosis [odd ratio (OR), 8.10, P 300 cm3 had 10 times higher odds of skin necrosis (OR, 10.66, P =0.010). Volumes >400 cm3 had 15 times higher odds of skin necrosis (OR, 15.56, P = 0.002). Mastectomy specimen weight was correlated with skin necrosis. Specimens >500 g had 10 times higher odds of necrosis and specimens >1000 g had 18 times higher odds of necrosis (OR, 10.03 and OR, 18.43; P =0.003 and P Mastectomy skin necrosis was associated with a 50% increased inpatient charge. Conclusion: Mastectomy flap necrosis is associated with HTN, larger TE volumes and mastectomy specimen weights, resulting in increased inpatient charges. Conservative TE volumes should be considered for patients with hypertension and larger mastectomy specimens. PMID:26301139

  6. Quantitatively characterizing the microstructural features of breast ductal carcinoma tissues in different progression stages by Mueller matrix microscope.

    Science.gov (United States)

    Dong, Yang; Qi, Ji; He, Honghui; He, Chao; Liu, Shaoxiong; Wu, Jian; Elson, Daniel S; Ma, Hui

    2017-08-01

    Polarization imaging has been recognized as a potentially powerful technique for probing the microstructural information and optical properties of complex biological specimens. Recently, we have reported a Mueller matrix microscope by adding the polarization state generator and analyzer (PSG and PSA) to a commercial transmission-light microscope, and applied it to differentiate human liver and cervical cancerous tissues with fibrosis. In this paper, we apply the Mueller matrix microscope for quantitative detection of human breast ductal carcinoma samples at different stages. The Mueller matrix polar decomposition and transformation parameters of the breast ductal tissues in different regions and at different stages are calculated and analyzed. For more quantitative comparisons, several widely-used image texture feature parameters are also calculated to characterize the difference in the polarimetric images. The experimental results indicate that the Mueller matrix microscope and the polarization parameters can facilitate the quantitative detection of breast ductal carcinoma tissues at different stages.

  7. Plasma and tissue levels of lipids, fatty acids and plasma carnitine in neonates receiving a new fat emulsion.

    Science.gov (United States)

    Magnusson, G; Boberg, M; Cederblad, G; Meurling, S

    1997-06-01

    This study was undertaken to compare Intralipid with a new fat emulsion containing gamma-linolenic acid and carnitine, named Pediatric Fat Emulsion 4501, in neonates with regard to lipid and carnitine metabolism over a short period of total parenteral nutrition. There were 10 neonates in each group and they tolerated the total parenteral nutrition well. In spite of the gamma-linolenic acid supplementation in the new emulsion, arachidonic acid decreased significantly in plasma lipid esters and adipose tissue in both groups after 5 d of treatment. Also, there was a decrease in plasma docosahexaenoic acid which was more pronounced in the treatment group. The relative percentage values of linoleic and linolenic acids in adipose tissue were increased, indicating that newborns have a rapid accretion of fatty acids. Plasma-triglycerides were effectively cleared during the periods without fat infusion. In the group that received Pediatric Fat Emulsion 4501 the means of both free and total plasma carnitine concentrations increased significantly, whereas they tended to decrease in the Intralipid group.

  8. Pharmacokinetic study of arctigenin in rat plasma and organ tissue by RP-HPLC method.

    Science.gov (United States)

    He, Fan; Dou, De-Qiang; Hou, Qiang; Sun, Yu; Kang, Ting-Guo

    2013-01-01

    A high-performance liquid chromatography (HPLC) technique was developed for the determination of arctigenin in plasma and various organs of rats after the oral administration of 30, 50 and 70 mgkg(-1) of arctigenin to the Sprague-Dawley rats. Results showed that the validated HPLC method was simple, fast, reproducible and suitable to the determination of arctigenin in rat plasma and organ tissue and one-compartmental model with zero-order absorption process can well describe the changes of arctigenin concentration in the plasma. The concentration of compound was highest in the spleen, less in the liver and the least in the lung.

  9. Impact of plasma fibrinogen levels in benign and malignant soft tissue tumors.

    Science.gov (United States)

    Asanuma, Kunihiro; Matsumine, Akihiko; Nakamura, Tomoki; Matsubara, Takao; Asanuma, Yumiko; Oi, Toru; Goto, Mikinobu; Okuno, Kazuma; Kakimoto, Takuya; Yada, Yuuki; Sudo, Akihiro

    2016-01-01

    Fibrinogen, a 340 kDa glycoprotein synthesized in the liver, is known to be involved in tumor angiogenesis, enlargement, and metastasis. Elevated plasma fibrinogen levels are associated with tumor progression in many cancer patients. However, there are no reports about differences in fibrinogen levels between benign and malignant soft tissue tumors. The purpose of this study was to clarify whether preoperative plasma fibrinogen levels can be used for differential diagnosis of benign or malignant soft tissue tumors. The plasma fibrinogen levels from 102 primary soft tissue tumor patients were measured before biopsy or treatment. Fibrinogen levels were analyzed and compared to various clinical parameters. According to receiver operating characteristic (ROC) curve analysis, a threshold of serum fibrinogen of 315 mg/dL identified malignant patients with 60.9% sensitivity and 87.5% specificity. The diagnostic accuracy was evaluated by area under the curve (AUC: 0.805). Over 315 mg/dL of fibrinogen was associated with a significantly increased risk of malignancy by multiple logistic regression analysis (OR: 6.452, p= 0.0004). We demonstrated that plasma fibrinogen levels have a relationship with tumor malignancy of soft tissue tumors. High fibrinogen levels can be a helpful subsidiary tool for the prediction of malignant soft tissue tumors with other diagnostic tools.

  10. Disposition of ampicillin trihydrate in plasma, uterine tissue, lochial fluid, and milk of postpartum dairy cattle.

    Science.gov (United States)

    Credille, B C; Giguère, S; Vickroy, T W; Fishman, H J; Jones, A L; Mason, M E; DiPietro, R O; Ensley, D T

    2015-08-01

    The objective of this study was to determine the disposition of ampicillin in plasma, uterine tissue, lochial fluid, and milk of postpartum dairy cattle. Ampicillin trihydrate was administered by intramuscular (i.m.) injection at a dose of 11 mg/kg of body weight every 24 h (n = 6, total of 3 doses) or every 12 h (n = 6, total of 5 doses) for 3 days. Concentrations of ampicillin were measured in plasma, uterine tissue, lochial fluid, and milk using HPLC with ultraviolet absorption. Quantifiable ampicillin concentrations were found in plasma, milk, and lochial fluid of all cattle within 30 min, 4 h, and 4 h of administration of ampicillin trihydrate, respectively. There was no significant effect of dosing interval (every 12 vs. every 24 h) and no significant interactions between dosing interval and sampling site on the pharmacokinetic variable measured or calculated. Median peak ampicillin concentration at steady-state was significantly higher in lochial fluid (5.27 μg/mL after q 24 h dosing) than other body fluids or tissues and significantly higher in plasma (3.11 μg/mL) compared to milk (0.49 μg/mL) or endometrial tissue (1.55 μg/mL). Ampicillin trihydrate administered once daily by the i.m. route at the label dose of 11 mg/kg of body weight achieves therapeutic concentrations in the milk, lochial fluid, and endometrial tissue of healthy postpartum dairy cattle.

  11. Similarity of Fibroglandular Breast Tissue Content Measured from Magnetic Resonance and Mammographic Images and by a Mathematical Algorithm

    Directory of Open Access Journals (Sweden)

    Fatima Nayeem

    2014-01-01

    Full Text Available Women with high breast density (BD have a 4- to 6-fold greater risk for breast cancer than women with low BD. We found that BD can be easily computed from a mathematical algorithm using routine mammographic imaging data or by a curve-fitting algorithm using fat and nonfat suppression magnetic resonance imaging (MRI data. These BD measures in a strictly defined group of premenopausal women providing both mammographic and breast MRI images were predicted as well by the same set of strong predictor variables as were measures from a published laborious histogram segmentation method and a full field digital mammographic unit in multivariate regression models. We also found that the number of completed pregnancies, C-reactive protein, aspartate aminotransferase, and progesterone were more strongly associated with amounts of glandular tissue than adipose tissue, while fat body mass, alanine aminotransferase, and insulin like growth factor-II appear to be more associated with the amount of breast adipose tissue. Our results show that methods of breast imaging and modalities for estimating the amount of glandular tissue have no effects on the strength of these predictors of BD. Thus, the more convenient mathematical algorithm and the safer MRI protocols may facilitate prospective measurements of BD.

  12. Application of computer-extracted breast tissue texture features in predicting false-positive recalls from screening mammography

    Science.gov (United States)

    Ray, Shonket; Choi, Jae Y.; Keller, Brad M.; Chen, Jinbo; Conant, Emily F.; Kontos, Despina

    2014-03-01

    Mammographic texture features have been shown to have value in breast cancer risk assessment. Previous models have also been developed that use computer-extracted mammographic features of breast tissue complexity to predict the risk of false-positive (FP) recall from breast cancer screening with digital mammography. This work details a novel locallyadaptive parenchymal texture analysis algorithm that identifies and extracts mammographic features of local parenchymal tissue complexity potentially relevant for false-positive biopsy prediction. This algorithm has two important aspects: (1) the adaptive nature of automatically determining an optimal number of region-of-interests (ROIs) in the image and each ROI's corresponding size based on the parenchymal tissue distribution over the whole breast region and (2) characterizing both the local and global mammographic appearances of the parenchymal tissue that could provide more discriminative information for FP biopsy risk prediction. Preliminary results show that this locallyadaptive texture analysis algorithm, in conjunction with logistic regression, can predict the likelihood of false-positive biopsy with an ROC performance value of AUC=0.92 (pclinical implications of using prediction models incorporating these texture features may include the future development of better tools and guidelines regarding personalized breast cancer screening recommendations. Further studies are warranted to prospectively validate our findings in larger screening populations and evaluate their clinical utility.

  13. Markers of fibrosis and epithelial to mesenchymal transition demonstrate field cancerization in histologically normal tissue adjacent to breast tumors

    Science.gov (United States)

    Trujillo, Kristina A.; Heaphy, Christopher M.; Mai, Minh; Vargas, Keith M.; Jones, Anna C.; Vo, Phung; Butler, Kimberly S.; Joste, Nancy E.; Bisoffi, Marco; Griffith, Jeffrey K

    2011-01-01

    Previous studies have shown that a field of genetically altered but histologically normal tissue extends 1 cm or more from the margins of human breast tumors. The extent, composition and biological significance of this field are only partially understood, but the molecular alterations in affected cells could provide mechanisms for limitless replicative capacity, genomic instability and a microenvironment that supports tumor initiation and progression. We demonstrate by microarray, qRT-PCR and immunohistochemistry a signature of differential gene expression that discriminates between patient-matched, tumor-adjacent histologically normal breast tissues located 1 cm and 5 cm from the margins of breast adenocarcinomas (TAHN-1 and TAHN-5, respectively). The signature includes genes involved in extracellular matrix remodeling, wound healing, fibrosis and epithelial to mesenchymal transition (EMT). Myofibroblasts, which are mediators of wound healing and fibrosis, and intra-lobular fibroblasts expressing MMP2, SPARC, TGF-β3, which are inducers of EMT, were both prevalent in TAHN-1 tissues, sparse in TAHN-5 tissues, and absent in normal tissues from reduction mammoplasty. Accordingly, EMT markers S100A4 and vimentin were elevated in both luminal and myoepithelial cells, and EMT markers α-smooth muscle actin and SNAIL were elevated in luminal epithelial cells of TAHN-1 tissues. These results identify cellular processes that are differentially activated between TAHN-1 and TAHN-5 breast tissues, implicate myofibroblasts as likely mediators of these processes, provide evidence that EMT is occurring in histologically normal tissues within the affected field and identify candidate biomarkers to investigate whether or how field cancerization contributes to the development of primary or recurrent breast tumors. PMID:21105047

  14. Plasma effects in electromagnetic field interaction with biological tissue

    Science.gov (United States)

    Sharma, R. P.; Batra, Karuna; Excell, Peter S.

    2011-02-01

    Theoretical analysis is presented of the nonlinear behavior of charge carriers in biological tissue under the influence of varying low-intensity electromagnetic (EM) field. The interaction occurs because of the nonlinear force arising due to the gradient of the EM field intensity acting on free electrons in the conduction band of proteins in metabolically active biological cell membrane receptors leading to a redistribution of charge carriers. Field dependence of the resulting dielectric constant is investigated by a suitable modification to include an additional electronic contribution term to the three-term Debye model. The exogenous EM field propagating in this nonlinear cellular medium satisfies the nonlinear Schrödinger equation and can be affected significantly. Resulting field effect can be substantially augmented and effective rectification/demodulation can occur. Possible implications of this modification on biological processes in white and grey matter are discussed.

  15. Evaluation of breast tissue with confocal strip-mosaicking microscopy: a test approach emulating pathology-like examination

    Science.gov (United States)

    Abeytunge, Sanjee; Larson, Bjorg; Peterson, Gary; Morrow, Monica; Rajadhyaksha, Milind; Murray, Melissa P.

    2017-03-01

    Confocal microscopy is an emerging technology for rapid imaging of freshly excised tissue without the need for frozen- or fixed-section processing. Initial studies have described imaging of breast tissue using fluorescence confocal microscopy with small regions of interest, typically 750×750 μm2. We present exploration with a microscope, termed confocal strip-mosaicking microscope (CSM microscope), which images an area of 2×2 cm2 of tissue with cellular-level resolution in 10 min of excision. Using the CSM microscope, we imaged 34 fresh, human, large breast tissue specimens from 18 patients, blindly analyzed by a board-certified pathologist and subsequently correlated with the corresponding standard fixed histopathology. Invasive tumors and benign tissue were clearly identified in CSM strip-mosaic images. Thirty specimens were concordant for image-to-histopathology correlation while four were discordant.

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

    Institute of Scientific and Technical Information of China (English)

    Mingxun Chen; Mengquan Li; Jingruo Li

    2009-01-01

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

  17. Plasma kinetics, tissue distribution, and cerebrocortical sources of reverse triiodothyronine in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Obregon, M.J.; Larsen, P.R.; Silva, J.E.

    1985-06-01

    Studies in vitro have shown that rT3 is a potent and competitive inhibitor of T4 5'-deiodination (5'D). Recent studies in vivo have shown that cerebrocortical (Cx) T4 5'D-type II (5'D-II) activity (propylthiouracil (PTU) insensitive pathway), is reduced by T4 and rT3, the latter being more potent than T3 in Cx 5'D-II suppression. Some other reports had described rT3 production in rat brain as a very active pathway of thyroid hormone metabolism. To examine the possibility that rT3 plays a physiological role in regulating Cx 5'D-II, we have explored rT3 plasma kinetics, plasma to tissue exchange, and uptake by tissues in the rat, as well as the metabolic routes of degradation and the sources of rT3 in cerebral cortex (Cx). Plasma and tissue levels were assessed with tracer (/sup 125/I)rT3. Two main compartments were defined by plasma disappearance curves in euthyroid rats (K/sub 1/ = -6.2 h-1 and K/sub 2/ = -0.75 h-1). In Cx of euthyroid rats, (/sup 125/I)rT3 peaked 10 min after iv injection, tissue to plasma ratio being 0.016 +/- 0.004 (SE). In thyroidectomized rats, plasma and tissue (/sup 125/I)rT3 concentrations were higher than in euthyroid rats, except for the Cx that did not change. PTU caused further increases in all the tissues studied, except for the Cx and the pituitaries of thyroidectomized rats. From the effect of blocking 5'D-I with PTU or reducing its activity by making the animals hypothyroid, we concluded that 5'D-I accounts for most of the rT3 clearance from plasma. In contrast, in Cx and pituitary the levels of rT3 seem largely affected by 5'D-II activity. Since the latter results suggest that plasma rT3 does not play a major role in determining rT3 levels in these tissues, we explored the sources of rT3 in Cx using (/sup 125/I)T4. The (/sup 125/I)rT3 (T4) to (/sup 125/I)T4 ratio remained constant at 0.03 from 1 up to 5 h after injection of (/sup 125/I)T4.

  18. A prospective study of XRCC1 haplotypes and their interaction with plasma carotenoids on breast cancer risk

    Energy Technology Data Exchange (ETDEWEB)

    Mohrenweiser, H W; Han, J; Hankinson, S E; De Vivo, I; Spiegelman, D; Tamimi, R M; Colditz, G A; Hunter, D J

    2004-01-15

    The XRCC1 protein is involved in the base excision repair pathway through interactions with other proteins. Polymorphisms in the XRCC1 gene may lead to variation in repair proficiency and confer inherited predisposition to cancer. We prospectively assessed the associations between polymorphisms and haplotypes in XRCC1 and breast cancer risk in a nested case-control study within the Nurses' Health Study (incident cases, n 1004; controls, n 1385). We further investigated gene-environment interactions between the XRCC1 variations and plasma carotenoids on breast cancer risk. We genotyped four haplotype-tagging single nucleotide polymorphisms Arg {sup 194}Trp, C26602T, Arg{sup 399}Gln, and Gln{sup 632}Gln in the XRCC1 gene. Five common haplotypes accounted for 99% of the chromosomes in the present study population of mostly Caucasian women. We observed a marginally significant reduction in the risk of breast cancer among {sup 194}Trp carriers. As compared with no-carriers, women with at least one {sup 194}Trp allele had a multivariate odds ratio of 0.79 (95% of the confidence interval, 0.60 -1.04). The inferred haplotype harboring the {sup 194}Trp allele was more common in controls than in cases (6.6 versus 5.3%, P 0.07). We observed that the Arg {sup 194}Trp modified the inverse associations of plasma -carotene level (P, ordinal test for interaction 0.02) and plasma -carotene level (P, ordinal test for interaction 0.003) with breast cancer risk. No suggestion of an interaction was observed between the Arg {sup 194}Trp and cigarette smoking. Our results suggest an inverse association between XRCC1 {sup 194}Trp allele and breast cancer risk. The findings of the effect modification of the Arg {sup 194}Trp on the relations of plasma -and -carotene levels with breast cancer risk suggest a potential protective effect of carotenoids in breast carcinogenesis by preventing oxidative DNA damage.

  19. Contribution of endothelial precursors of adipose tissue to breast cancer: progression-link with fat graft for reconstructive surgery.

    Science.gov (United States)

    Bertolini, Francesco

    2013-05-01

    Obesity, an excess accumulation of adipose tissue occurring in mammalians when caloric intake exceeds energy expenditure, is associated with an increased frequency and progression of several types of neoplastic diseases including postmenopausal breast cancer. Recent studies have suggested that obesity-related disruption of the energy homeostasis results in inflammation and alterations of adipokine signalling that may foster cancer initiation and progression. Moreover, two populations of human white adipose tissue (WAT) progenitors cooperate in breast cancer angiogenesis, growth and metastatic progression. This raises the issue of lipotransfer in patients undergoing plastic or reconstructive surgery.

  20. Levels of plasma circulating cell free nuclear and mitochondrial DNA as potential biomarkers for breast tumors

    Directory of Open Access Journals (Sweden)

    Diesch Claude

    2009-11-01

    Full Text Available Abstract Background With the aim to simplify cancer management, cancer research lately dedicated itself more and more to discover and develop non-invasive biomarkers. In this connection, circulating cell-free DNA (ccf DNA seems to be a promising candidate. Altered levels of ccf nuclear DNA (nDNA and mitochondrial DNA (mtDNA have been found in several cancer types and might have a diagnostic value. Methods Using multiplex real-time PCR we investigated the levels of ccf nDNA and mtDNA in plasma samples from patients with malignant and benign breast tumors, and from healthy controls. To evaluate the applicability of plasma ccf nDNA and mtDNA as a biomarker for distinguishing between the three study-groups we performed ROC (Receiver Operating Characteristic curve analysis. We also compared the levels of both species in the cancer group with clinicopathological parameters. Results While the levels of ccf nDNA in the cancer group were significantly higher in comparison with the benign tumor group (P P P P = 0.022. The level of ccf nDNA was also associated with tumor-size (2 cmP = 0.034. Using ROC curve analysis, we were able to distinguish between the breast cancer cases and the healthy controls using ccf nDNA as marker (cut-off: 1866 GE/ml; sensitivity: 81%; specificity: 69%; P P Conclusion Our data suggests that nuclear and mitochondrial ccf DNA have potential as biomarkers in breast tumor management. However, ccf nDNA shows greater promise regarding sensitivity and specificity.

  1. Large-scale inference of protein tissue origin in gram-positive sepsis plasma using quantitative targeted proteomics.

    Science.gov (United States)

    Malmström, Erik; Kilsgård, Ola; Hauri, Simon; Smeds, Emanuel; Herwald, Heiko; Malmström, Lars; Malmström, Johan

    2016-01-06

    The plasma proteome is highly dynamic and variable, composed of proteins derived from surrounding tissues and cells. To investigate the complex processes that control the composition of the plasma proteome, we developed a mass spectrometry-based proteomics strategy to infer the origin of proteins detected in murine plasma. The strategy relies on the construction of a comprehensive protein tissue atlas from cells and highly vascularized organs using shotgun mass spectrometry. The protein tissue atlas was transformed to a spectral library for highly reproducible quantification of tissue-specific proteins directly in plasma using SWATH-like data-independent mass spectrometry analysis. We show that the method can determine drastic changes of tissue-specific protein profiles in blood plasma from mouse animal models with sepsis. The strategy can be extended to several other species advancing our understanding of the complex processes that contribute to the plasma proteome dynamics.

  2. Concentrations of danofloxacin 18% solution in plasma, milk and tissues after subcutaneous injection in dairy cows

    Energy Technology Data Exchange (ETDEWEB)

    Mestorino, N. [Pharmacology Department, Faculty of Veterinary Science, Universidad Nacional de La Plata, CC 296, 1900 La Plata, Buenos Aires (Argentina)], E-mail: nmestorino@yahoo.com; Marchetti, M.L.; Turic, E.; Pesoa, J.; Errecalde, J. [Pharmacology Department, Faculty of Veterinary Science, Universidad Nacional de La Plata, CC 296, 1900 La Plata, Buenos Aires (Argentina)

    2009-04-01

    Danofloxacin is a fluoroquinolone developed for use in veterinary medicine. Its concentrations and pharmacokinetic profile in plasma, milk and tissues of lactating dairy cows were determined, and its milk withdrawal time (WT) calculated. Twenty-one dairy cows received a single subcutaneous administration of 18% mesylate danofloxacin salt (6 mg kg{sup -1}). Plasma and milk samples were obtained at different times until 48 h. Groups of three animals were sacrificed at different post-administration times and tissue samples (mammary gland, uterus, duodenum, jejunum, ileum, colon and mesenteric lymph nodes) obtained. Danofloxacin concentrations were determined by liquid chromatography with fluorescence detection. The milk WT was calculated by the Time to Safe Concentration method (Software WTM 1.4, EMEA). Danofloxacin was rapidly absorbed and its distribution from plasma to all sampled tissues and milk was extensive. Milk and tissues concentrations were several times above those found in plasma. Plasma area under the curve (AUCp) was 9.69 {mu}g h mL{sup -1} and its elimination half life (T{sub {beta}}{sup 1/2}) was 12.53 h. AUC values for the various tissues and milk greatly exceeded AUCp. T{sub {beta}}{sup 1/2} from milk and tissues ranged between 4.57 and 21.91 h and the milk withdrawal time was 73.48 h. The reported results support the potential use of danofloxacin in the treatment of mastitis and other infections in milk cows with 3 days of withdrawal.

  3. Resistin in dairy cows: plasma concentrations during early lactation, expression and potential role in adipose tissue.

    Directory of Open Access Journals (Sweden)

    Maxime Reverchon

    Full Text Available Resistin is an adipokine that has been implicated in energy metabolism regulation in rodents but has been little studied in dairy cows. We determined plasma resistin concentrations in early lactation in dairy cows and investigated the levels of resistin mRNA and protein in adipose tissue and the phosphorylation of several components of insulin signaling pathways one week post partum (1 WPP and at five months of gestation (5 MG. We detected resistin in mature bovine adipocytes and investigated the effect of recombinant bovine resistin on lipolysis in bovine adipose tissue explants. ELISA showed that plasma resistin concentration was low before calving, subsequently increasing and reaching a peak at 1 WPP, decreasing steadily thereafter to reach pre-calving levels at 6 WPP. Plasma resistin concentration was significantly positively correlated with plasma non esterified fatty acid (NEFA levels and negatively with milk yield, dry matter intake and energy balance between WPP1 to WPP22. We showed, by quantitative RT-PCR and western blotting, that resistin mRNA and protein levels in adipose tissue were higher at WPP1 than at 5 MG. The level of phosphorylation of several early and downstream insulin signaling components (IRβ, IRS-1, IRS-2, Akt, MAPK ERK1/2, P70S6K and S6 in adipose tissue was also lower at 1 WPP than at 5 MG. Finally, we showed that recombinant bovine resistin increased the release of glycerol and mRNA levels for ATGL (adipose triglyceride lipase and HSL (hormone-sensitive lipase in adipose tissue explants. Overall, resistin levels were high in the plasma and adipose tissue and were positively correlated with NEFA levels after calving. Resistin is expressed in bovine mature adipocytes and promotes lipid mobilization in adipose explants in vitro.

  4. X-ray phase-contrast tomosynthesis for improved breast tissue discrimination

    Energy Technology Data Exchange (ETDEWEB)

    Schleede, Simone, E-mail: Schleede@tum.de [Department of Physics and Institute of Medical Engineering, Technische Universität München, James-Franck-Strasse 1, 85748 Garching (Germany); Bech, Martin, E-mail: martin.bech@tum.de [Department of Physics and Institute of Medical Engineering, Technische Universität München, James-Franck-Strasse 1, 85748 Garching (Germany); Medical Radiation Physics, Lund University, 22185 Lund (Sweden); Grandl, Susanne, E-mail: Susanne.Grandl@med.uni-muenchen.de [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Marchioninistr. 15, 81377 München (Germany); Sztrókay, Aniko, E-mail: Aniko.Sztrokay@med.uni-muenchen.de [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Marchioninistr. 15, 81377 München (Germany); Herzen, Julia, E-mail: julia.herzen@hzg.de [Institute of Materials Research, Helmholtz-Zentrum Geesthacht, Max-Planck-Strasse 1, 21502 Geesthacht (Germany); Mayr, Doris, E-mail: doris.mayr@med.uni-muenchen.de [Institute of Pathology, Ludwig-Maximilians-Universität München, Thalkirchner Str. 36, 80337 Munich (Germany); Stockmar, Marco, E-mail: marco.stockmar@ph.tum.de [Department of Physics and Institute of Medical Engineering, Technische Universität München, James-Franck-Strasse 1, 85748 Garching (Germany); Potdevin, Guillaume, E-mail: potdevinguillaume@gmail.com [Department of Physics and Institute of Medical Engineering, Technische Universität München, James-Franck-Strasse 1, 85748 Garching (Germany); and others

    2014-03-15

    Purpose: Attenuation-based tomosynthesis has proven to successfully resolve the glandular tissue overlap present in mammography. However, the ability of tomosynthesis to differentiate tumorous and glandular tissue remains limited, due to the small differences in X-ray attenuation in breast tissue. One possibility to overcome this limitation and to further increase the diagnostic value of tomosynthesis exams, is the application of recently developed grating-based phase-contrast methods, which provide complementary information on the phase shift and the local scattering power of the sample. In this study, we report on first phase-contrast breast tomosynthesis results of a mastectomy sample slice with an invasive ductal carcinoma. Material and methods: A slice of a mastectomy sample with histologically proven invasive ductal cancer was imaged at the synchrotron radiation source ESRF (Grenoble, France). We used a two-grating interferometer setup at the ninth fractional Talbot distance and with an X-ray energy of 23 keV. In grating interferometry absorption, differential phase, and scattering images are recorded simultaneously. The tomosynthesis scan comprises 61 projections. Multimodal tomosynthesis results were reconstructed using a standard filtered back-projection approach. Our findings are supported by a comparison of tomographic views to histopathology. Results: Phase-contrast tomosynthesis combines the advantage of improved soft-tissue discrimination in phase-contrast imaging with the ability of tomosynthesis to provide a third dimension so that improved feature visibility is not hampered by superposition artifacts. Our results indicate superior diagnostic value due to the depth resolution supplied in tomosynthesis imaging; a region of necrotic tissue that is obscured in a projection image can clearly be depicted in one single tomosynthesis slice. Compared to absorption tomosynthesis alone, soft tissue contrast is significantly enhanced in phase

  5. A plasma scalpel: comparison of tissue damage and wound healing with electrosurgical and steel scalpels.

    Science.gov (United States)

    Link, W J; Incropera, F P; Glover, J L

    1976-04-01

    We have been evaluating a plasma scalpel (the term has no relation to blood plasma) for four years that, with the generation of a small, hot gas jet (3,000 C), can cut tissue and simultaneously cauterize blood vessels of 3 mm in diameter. Twenty-nine plasma scalpel hepatectomies in dogs and comparative skin wound healing (with steel and electrosurgical scalpels) in 90 mice showed that bleeding was reduced, and the thermal insult in liver tissue was limited to 2 mm from the incision; both liver and mouse skin incisions healed without complication. The completion of epithelization of mouse skin wounds occurred at 2 to 6, 6 to 14, and 6 to 18 days, and the average scar width was 0.8, 1.4, and 2.1 mm for the steel, electrosurgical, and plasma scalpels, respectively. The plasma scalpel effectively cauterizes blood vessels as it cuts, leaving limited damaged tissue. We have recently begun human trials, and the device shows promise as a clinical tool.

  6. Calculation of dose distribution in compressible breast tissues using finite element modeling, Monte Carlo simulation and thermoluminescence dosimeters

    Science.gov (United States)

    Mohammadyari, Parvin; Faghihi, Reza; Mosleh-Shirazi, Mohammad Amin; Lotfi, Mehrzad; Rahim Hematiyan, Mohammad; Koontz, Craig; Meigooni, Ali S.

    2015-12-01

    Compression is a technique to immobilize the target or improve the dose distribution within the treatment volume during different irradiation techniques such as AccuBoost® brachytherapy. However, there is no systematic method for determination of dose distribution for uncompressed tissue after irradiation under compression. In this study, the mechanical behavior of breast tissue between compressed and uncompressed states was investigated. With that, a novel method was developed to determine the dose distribution in uncompressed tissue after irradiation of compressed breast tissue. Dosimetry was performed using two different methods, namely, Monte Carlo simulations using the MCNP5 code and measurements using thermoluminescent dosimeters (TLD). The displacement of the breast elements was simulated using a finite element model and calculated using ABAQUS software. From these results, the 3D dose distribution in uncompressed tissue was determined. The geometry of the model was constructed from magnetic resonance images of six different women volunteers. The mechanical properties were modeled by using the Mooney-Rivlin hyperelastic material model. Experimental dosimetry was performed by placing the TLD chips into the polyvinyl alcohol breast equivalent phantom. The results determined that the nodal displacements, due to the gravitational force and the 60 Newton compression forces (with 43% contraction in the loading direction and 37% expansion in the orthogonal direction) were determined. Finally, a comparison of the experimental data and the simulated data showed agreement within 11.5%  ±  5.9%.

  7. Sustained regeneration of high-volume adipose tissue for breast reconstruction using computer aided design and biomanufacturing.

    Science.gov (United States)

    Chhaya, Mohit Prashant; Melchels, Ferry Petrus Wilhelmus; Holzapfel, Boris Michael; Baldwin, Jeremy Grant; Hutmacher, Dietmar Werner

    2015-06-01

    Adipose tissue engineering offers a promising alternative to the current breast reconstruction options. Here we investigated patient-specific breast scaffolds fabricated from poly(d,l)-lactide polymer with pore sizes>1 mm for their potential in long-term sustained regeneration of high volume adipose tissue. An optimised scaffold geometry was modelled in silico via a laser scanning data set from a patient who underwent breast reconstruction surgery. After the design process scaffolds were fabricated using an additive manufacturing technology termed fused deposition modelling. Breast-shaped scaffolds were seeded with human umbilical cord perivascular cells and cultured under static conditions for 4 weeks and subsequently 2 weeks in a biaxial rotating bioreactor. These in vitro engineered constructs were then seeded with human umbilical vein endothelial cells and implanted subcutaneously into athymic nude rats for 24 weeks. Angiogenesis and adipose tissue formation were observed throughout all constructs at all timepoints. The percentage of adipose tissue compared to overall tissue area increased from 37.17% to 62.30% between week 5 and week 15 (pbreast reconstruction. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Comparison of Patient-reported Outcomes after Implant Versus Autologous Tissue Breast Reconstruction Using the BREAST-Q

    OpenAIRE

    Pirro, Ortensia; Mestak, Ondrej; Vindigni, Vincenzo; Sukop, Andrej; Hromadkova, Veronika; Nguyenova, Alena; Vitova, Lenka; Bassetto, Franco

    2017-01-01

    Background: The demand for reconstructive breast procedures of various types has accelerated in recent years. Coupled with increased patient expectations, it has fostered the development of oncoplastic and reconstructive techniques in breast surgery. In the setting of postmastectomy reconstruction, patient satisfaction and quality of life are the most significant outcome variables when evaluating surgical success. The aim of this study was to evaluate the quality of life after implant breast ...

  9. An investigation of plasma and salivary oxytocin responses in breast- and formula-feeding mothers of infants

    OpenAIRE

    Grewen, Karen M.; DAVENPORT, RUSSELL E.; Light, Kathleen C.

    2010-01-01

    Oxytocin (OT) is a peptide increasingly studied in relation to human social interactions, affiliation, and clinical disorders. Studies are constrained by use of invasive blood draws and would benefit from a reliable salivary OT assay. Our goals were to examine feasibility of salivary OT measurement, compare salivary to plasma OT responses in 12 breast- and 8 formula-feeding mothers, and assess the degree of correlation between plasma and salivary OT. Using a commercial EIA kit, we measured OT...

  10. Effect of GFR on plasma N-terminal connective tissue growth factor (CTGF) concentrations.

    NARCIS (Netherlands)

    Gerritsen, K.G.; Abrahams, A.C.; Peters, H.P.E.; Nguyen, T.Q.; Koeners, M.P.; Hoedt, C.H. den; Dendooven, A.; Dorpel, M.A. van den; Blankestijn, P.J.; Wetzels, J.F.M.; Joles, J.A.; Goldschmeding, R.; Kok, R.J.

    2012-01-01

    BACKGROUND: Connective tissue growth factor (CTGF) has a key role in the pathogenesis of renal and cardiac fibrosis. Its amino-terminal fragment (N-CTGF), the predominant form of CTGF detected in plasma, has a molecular weight in the middle molecular range (18 kDa). However, it is unknown whether N-

  11. Assessment of the biological variation of plasma tissue inhibitor of metalloproteinases-1

    DEFF Research Database (Denmark)

    2008-01-01

    BACKGROUND: Tissue inhibitor of metalloproteinases-1 (TIMP-1) measurements in plasma may be useful for the early detection and prognosis of colorectal cancer (CRC). Data on analytical performance and normal intra- and interindividual biological variation are required in order to interpret the uti...

  12. Chemotherapy modulates the biological activity of breast cancer patients plasma: the protective properties of black chokeberry extract.

    Science.gov (United States)

    Kędzierska, Magdalena; Malinowska, Joanna; Kontek, Bogdan; Kołodziejczyk-Czepas, Joanna; Czernek, Urszula; Potemski, Piotr; Piekarski, Janusz; Jeziorski, Arkadiusz; Olas, Beata

    2013-03-01

    In breast cancer patients (before and during anti-cancer therapy) oxidative/nitrative damage to various molecules is observed. Furthermore, anti-cancer treatments may also influence the hemostatic properties of blood platelets and plasma. The aim of our study was to assess the effect of oxidative/nitrative stress (estimated by measurements of the levels of carbonyl groups and 3-nitrotyrosine in proteins--ELISA and C-ELISA methods, respectively; lipid peroxidation and total antioxidant level--TAS) on the selected parameters of hemostatic activity of plasma (the process of fibrin polymerization and lysis) collected from breast cancer patients after surgery and after various phases of chemotherapy (doxorubicin and cyclophosphamide). Subsequently, we also evaluated the level of oxidative/nitrative stress and hemostatic activity in plasma from these patients in the presence of the commercial extract of Aronia melanocarpa (Aronox®) in vitro. Patients were hospitalized in Department of Oncological Surgery and Department of Chemotherapy in Medical University of Lodz, Poland. We observed increased levels of biomarkers of oxidative/nitrative stress in plasma from patients with breast cancer (before or after surgery and after various phases of chemotherapy) in comparison to healthy group. Our further experiments demonstrated the hemostatic activity of plasma from the investigated patients differs from hemostatic properties of plasma obtained from healthy volunteers. We also recognize the existence of a relationship between oxidative stress (measured by the level of carbonyl groups) and changes of hemostasis in breast cancer patients after I and IV phases of chemotherapy. Moreover, the obtained results showed that the commercial extract from A. melanocarpa berries significantly reduced, in in vitro system, the oxidative/nitrative stress and hemostasis changes in plasma from breast cancer patients, after surgery and different phases of chemotherapy. Considering the data

  13. YKL-40 tissue expression and plasma levels in patients with ovarian cancer

    DEFF Research Database (Denmark)

    Høgdall, Estrid V S; Ringsholt, Merete; Høgdall, Claus K;

    2009-01-01

    BACKGROUND: YKL-40 (chitinase-3-like-1) is a member of "mammalian chitinase-like proteins". The protein is expressed in many types of cancer cells and the highest plasma YKL-40 levels have been found in patients with metastatic disease, short recurrence/progression-free intervals, and short overall...... survival. The aim of the study was to determine the expression of YKL-40 in tumor tissue and plasma in patients with borderline ovarian tumor or epithelial ovarian cancer (OC), and investigate prognostic value of this marker. METHODS: YKL-40 protein expression was determined by immunohistochemistry...... in tissue arrays from 181 borderline tumors and 473 OC. Plasma YKL-40 was determined by ELISA in preoperative samples from 19 patients with borderline tumor and 76 OC patients. RESULTS: YKL-40 protein expression was found in cancer cells, tumor associated macrophages, neutrophils and mast cells. The tumor...

  14. Zinc in plasma and breast milk in adolescents and adults in pregnancy and pospartum: a cohort study in Uruguay

    Directory of Open Access Journals (Sweden)

    Cecilia Seven

    2013-02-01

    Full Text Available Objective: To assess if age is a risk factor for low zinc nutritional status in pregnancy, postpartum and in breast milk concentration, and the association between mother zinc plasma level with zinc milk concentration. Design: Cohort study comparing adolescents with adult women, with < 14 weeks of gestation at first prenatal care. Socio demographic and plasma zinc data were collected at that moment and at postpartum time (4 + 1 month. Milk zinc concentrations were also measured at 4th month postpartum. Setting: Women were recruited from 16 public primary health care services in Uruguay Subjects: 151 adolescents and 161 adult women Results: Adolescent average plasma zinc at < 14 weeks of gestation was 84.4 ± 3.6 μg /dl and did not differ significantly from that for adult women (85.2 ± 13.6 ug/dl. Prevalence of hypozincemia was relatively low with but with no difference by age (14.6% in adolescents and 12.3% in adults. Zinc concentrations in breast milk were similar for adolescents, 1.24 mg. /L (CI 1.06 to 1.44 and adult women, 1.27 mg./L (CI .1.0-1.46. There was no correlation between plasma zinc and breast milk zinc concentrations in adults and a weak correlation in adolescents (-0.27, p <0.05. Conclusions: Prevalence of hypozincemia in pregnancy was relatively low but similar in adolescents and adult women. Neither pregnancy nor age had negative consequences over postpartum plasma zinc, nor over breast milk zinc concentrations. No correlation was found between mother s plasma zinc and breast milk levels.

  15. Oxidative stress associated to dysfunctional adipose tissue: a potential link between obesity, type 2 diabetes mellitus and breast cancer.

    Science.gov (United States)

    Crujeiras, A B; Díaz-Lagares, A; Carreira, M C; Amil, M; Casanueva, F F

    2013-04-01

    Diabetes mellitus and breast cancer are two important health problems. Type 2 diabetes (T2DM) and obesity are closely linked with both being associated with breast cancer. Despite abundant epidemiological data, there is no definitive evidence regarding the mechanisms responsible for this association. The proposed mechanisms by which diabetes affects breast cancer risk and prognosis are the same as the mechanisms hypothesised for the contribution of obesity to breast cancer risk. The obesity-induced inflammation promoted by adipose tissue dysfunction is a key feature, which is thought to be an important link between obesity and cancer. Inflammation induces an increase in free radicals and subsequently promotes oxidative stress, which may create a microenvironment favourable to the tumor development in obese persons. Oxidative stress is also proposed as the link between obesity and diabetes mellitus. Therefore, obesity-related oxidative stress could be a direct cause of neoplastic transformation associated with obesity and T2DM in breast cancer cells. This review is focused on the role of obesity-related oxidative stress in the context of chronic inflammation, on the time of breast cancer onset and progression, which provide targets for preventive and therapeutic strategies in the fields of diabetes and obesity-related breast cancer.

  16. Comparison of Outcomes with Tissue Expander, Immediate Implant, and Autologous Breast Reconstruction in Greater Than 1000 Nipple-Sparing Mastectomies.

    Science.gov (United States)

    Frey, Jordan D; Choi, Mihye; Salibian, Ara A; Karp, Nolan S

    2017-06-01

    Nipple-sparing mastectomy permits complete preservation of the nipple-areola complex with excellent aesthetic results and with oncologic safety similar to that associated with traditional mastectomy techniques. However, outcomes have not been directly compared for tissue expander-, immediate implant-, and autologous tissue-based breast reconstruction after nipple-sparing mastectomy. All patients undergoing nipple-sparing mastectomy from 2006 to June of 2016 were identified at a single institution. Demographics and outcomes were analyzed and compared among different types of breast reconstruction. A total of 1028 nipple-sparing mastectomies were performed. Of these, 533 (51.8 percent) were tissue expander-based, 263 (25.6 percent) were autologous tissue-based, and 232 (22.6 percent) were immediate implant-based reconstructions. Tissue expander-based reconstructions had significantly more minor cellulitis (p = 0.0002) but less complete nipple necrosis (p = 0.0126) and major mastectomy flap necrosis (p < 0.0001) compared with autologous tissue-based reconstructions. Compared to immediate implant-based reconstruction, tissue expander-based reconstructions had significantly more minor cellulitis (p = 0.0006) but less complete nipple necrosis (p = 0.0005) and major (p < 0.0001) and minor (p = 0.0028) mastectomy flap necrosis (p = 0.0059). Immediate implant-based reconstructions had significantly more minor cellulitis (p = 0.0051), minor mastectomy flap necrosis (p = 0.0425), and partial nipple necrosis (p = 0.0437) compared with autologous tissue-based reconstructions. Outcomes were otherwise equivalent among the three groups. Tissue expander, immediate implant, and autologous tissue breast reconstruction techniques may all be safely offered with nipple-sparing mastectomy. However, reconstructive complications appear to be greater with immediate implant- and autologous tissue-based techniques compared with tissue expander-based reconstruction. Therapeutic, III.

  17. Plasma-modified and polyethylene glycol-grafted polymers for potential tissue engineering applications.

    Science.gov (United States)

    Svorcík, V; Makajová, Z; Kasálková-Slepicková, N; Kolská, Z; Bacáková, L

    2012-08-01

    Modified and grafted polymers may serve as building blocks for creating artificial bioinspired nanostructured surfaces for tissue engineering. Polyethylene (PE) and polystyrene (PS) were modified by Ar plasma and the surface of the plasma activated polymers was grafted with polyethylene glycol (PEG). The changes in the surface wettability (contact angle) of the modified polymers were examined by goniometry. Atomic Force Microscopy (AFM) was used to determine the surface roughness and morphology and electrokinetical analysis (Zeta potential) characterized surface chemistry of the modified polymers. Plasma treatment and subsequent PEG grafting lead to dramatic changes in the polymer surface morphology, roughness and wettability. The plasma treated and PEG grafted polymers were seeded with rat vascular smooth muscle cells (VSMCs) and their adhesion and proliferation were studied. Biological tests, performed in vitro, show increased adhesion and proliferation of cells on modified polymers. Grafting with PEG increases cell proliferation, especially on PS. The cell proliferation was shown to be an increasing function of PEG molecular weight.

  18. X-ray attenuation of adipose breast tissue: in-vitro and in-vivo measurements using spectral imaging

    Science.gov (United States)

    Fredenberg, Erik; Erhard, Klaus; Berggren, Karl; Dance, David R.; Young, Kenneth C.; Cederström, Björn; Johansson, Henrik; Lundqvist, Mats; Moa, Elin; Homan, Hanno; Willsher, Paula; Kilburn-Toppin, Fleur; Wallis, Matthew

    2015-03-01

    The development of new x-ray imaging techniques often requires prior knowledge of tissue attenuation, but the sources of such information are sparse. We have measured the attenuation of adipose breast tissue using spectral imaging, in vitro and in vivo. For the in-vitro measurement, fixed samples of adipose breast tissue were imaged on a spectral mammography system, and the energy-dependent x-ray attenuation was measured in terms of equivalent thicknesses of aluminum and poly-methyl methacrylate (PMMA). For the in-vivo measurement, a similar procedure was applied on a number of spectral screening mammograms. The results of the two measurements agreed well and were consistent with published attenuation data and with measurements on tissue-equivalent material.

  19. In vitro assessment of MRI issues at 3-Tesla for a breast tissue expander with a remote port.

    Science.gov (United States)

    Linnemeyer, Hannah; Shellock, Frank G; Ahn, Christina Y

    2014-04-01

    A patient with a breast tissue expander may require a diagnostic assessment using magnetic resonance imaging (MRI). To ensure patient safety, this type of implant must undergo in vitro MRI testing using proper techniques. Therefore, this investigation evaluated MRI issues (i.e., magnetic field interactions, heating, and artifacts) at 3-Tesla for a breast tissue expander with a remote port. A breast tissue expander with a remote port (Integra Breast Tissue Expander, Model 3612-06 with Standard Remote Port, PMT Corporation, Chanhassen, MN) underwent evaluation for magnetic field interactions (translational attraction and torque), MRI-related heating, and artifacts using standardized techniques. Heating was evaluated by placing the implant in a gelled-saline-filled phantom and MRI was performed using a transmit/receive RF body coil at an MR system reported, whole body averaged specific absorption rate of 2.9-W/kg. Artifacts were characterized using T1-weighted and GRE pulse sequences. Magnetic field interactions were not substantial and, thus, will not pose a hazard to a patient in a 3-Tesla or less MRI environment. The highest temperature rise was 1.7°C, which is physiologically inconsequential. Artifacts were large in relation to the remote port and metal connector of the implant but will only present problems if the MR imaging area of interest is where these components are located. A patient with this breast tissue expander with a remote port may safely undergo MRI at 3-Tesla or less under the conditions used for this investigation. These findings are the first reported at 3-Tesla for a tissue expander. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. c-erbB-2 protein level in tissue and sera of breast cancer patients: a possibly useful clinical correlation.

    Science.gov (United States)

    Quaranta, Michele; Daniele, Antonella; Coviello, Maria; Savonarola, Annalisa; Abbate, Ines; Venneri, Maria Teresa; Paradiso, Angelo; Stea, Baldassarre; Zito, Alfredo; Labriola, Angela; Schittulli, Francesco

    2006-01-01

    The aims of this study were to assess the clinical utility of circulating preoperative HER-2 extracellular domain p105 detected by enzyme immunoassay (ELISA), to compare the tissue expression of HER-2/neu determined by immunohistochemistry (IHC), to correlate prognostic factors including tumor size, nodal involvement, and hormone receptor status, and to analyze the prognostic significance of the marker in relation to clinical outcome as measured by disease-free and overall survival. In this study, we enrolled 108 consecutive patients with breast carcinoma, and obtained serum samples and frozen tumor tissues. We compared them with 57 women with fibroadenoma and 63 healthy women as controls. Univariate ANOVA analysis showed no relationship between HER-2/neu in tissue and serum. Preoperative serum levels of p105 were significantly higher in breast cancer patients than in women with benign disease or healthy women. Concerning the correlation between p105, HER-2/neu tissue expression, and the other prognostic factors, a statistically significant correlation between high serum p105 levels and ER-negative status in breast cancer patients was found. Kaplan-Meier analysis confirmed that patients with positive HER-2/neu tissue expression had a significantly shorter survival than those with negative expression. Analysis with the Cox model demonstrated that tumor size was the only significant independent prognostic factor. This research failed to demonstrate a relationship between preoperative tissue overexpression and circulating HER-2/neu, suggesting that p105 does not represent a valid alternative to predict a worsened prognosis in breast cancer, but it could be a diagnostic marker to discriminate healthy subjects from breast cancer patients.

  1. Evolution of the plasma and tissue kallikreins, and their alternative splicing isoforms.

    Directory of Open Access Journals (Sweden)

    Vassiliki Lila Koumandou

    Full Text Available Kallikreins are secreted serine proteases with important roles in human physiology. Human plasma kallikrein, encoded by the KLKB1 gene on locus 4q34-35, functions in the blood coagulation pathway, and in regulating blood pressure. The human tissue kallikrein and kallikrein-related peptidases (KLKs have diverse expression patterns and physiological roles, including cancer-related processes such as cell growth regulation, angiogenesis, invasion, and metastasis. Prostate-specific antigen (PSA, the product of the KLK3 gene, is the most widely used biomarker in clinical practice today. A total of 15 KLKs are encoded by the largest contiguous cluster of protease genes in the human genome (19q13.3-13.4, which makes them ideal for evolutionary analysis of gene duplication events. Previous studies on the evolution of KLKs have traced mammalian homologs as well as a probable early origin of the family in aves, amphibia and reptilia. The aim of this study was to address the evolutionary and functional relationships between tissue KLKs and plasma kallikrein, and to examine the evolution of alternative splicing isoforms. Sequences of plasma and tissue kallikreins and their alternative transcripts were collected from the NCBI and Ensembl databases, and comprehensive phylogenetic analysis was performed by Bayesian as well as maximum likelihood methods. Plasma and tissue kallikreins exhibit high sequence similarity in the trypsin domain (>50%. Phylogenetic analysis indicates an early divergence of KLKB1, which groups closely with plasminogen, chymotrypsin, and complement factor D (CFD, in a monophyletic group distinct from trypsin and the tissue KLKs. Reconstruction of the earliest events leading to the diversification of the tissue KLKs is not well resolved, indicating rapid expansion in mammals. Alternative transcripts of each KLK gene show species-specific divergence, while examination of sequence conservation indicates that many annotated human KLK isoforms

  2. Upregulation of Mrps18a in breast cancer identified by selecting phage antibody libraries on breast tissue sections

    DEFF Research Database (Denmark)

    Sørensen, Karen Marie Juul; Meldgaard, Theresa; Melchjorsen, Connie Jenning

    2017-01-01

    of recombinant antibody libraries displayed on the surface of filamentous bacteriophage as a proteomics discovery tool for the identification of breast cancer biomarkers. A small subpopulation of breast cells expressing both cytokeratin 19 and cytokeratin 14 was targeted using a novel selection procedure...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-09-29

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

  4. Wet autoclave pretreatment for immunohistochemical demonstration of oestrogen receptors in routinely processed breast carcinoma tissue.

    Science.gov (United States)

    Bier, B; Bankfalvi, A; Grote, L; Blasius, S; Ofner, D; Böcker, W; Jasani, B; Schmid, K W

    1995-02-01

    The immunohistochemical demonstration of oestrogen receptor (OR) was performed on 32 randomly selected and routinely processed breast carcinomas after wet autoclave pretreatment of sections. The autoclave method was compared to the OR status found on frozen sections as well as to alternative pretreatment methods such as enzymatic predigestion and microwave irradiation. Using four different monoclonal antibody clones (H222, LH1, CC4-5, 1D5.26), the OR status was evaluated for each of the various pretreatment methods applied. All cases with a high OR content on frozen sections (n = 11) also showed a high OR status on wet autoclave-pretreated paraffin tissues using antibody clones 1D5.26 and CC4-5; in cases with low OR content on frozen sections, no false-negative cases were recorded using only the antibody 1D5.26 neither after wet autoclave nor microwave pretreatment. In addition, with this antibody, OR was detectable after autoclave pretreatment in two cases which were considered to be OR-negative even on frozen sections. When the primary antibody was omitted, no false-positive cases were observed after wet autoclave pretreatment. Thus, in our hands, wet autoclave pretreatment, in combination with the antibody 1D5.26, offers a highly sensitive method for the immunohistochemical demonstration of OR in routinely formalin-fixed, paraffin-embedded sections of breast carcinomas.

  5. Effects of experimentally increased protein supply to postpartum dairy cows on plasma protein synthesis, rumen tissue proliferation, and immune homeostasis

    DEFF Research Database (Denmark)

    Larsen, Mogens; Røntved, Christine Maria; Theil, Peter Kappel

    2017-01-01

    enrichment in arterial plasma free Phe, total plasma proteins, and albumin after 3, 5, and 7 h of jugular ring[13C]Phe infusion. Plasma volume was determined at +4 and +29 DRTC by dilution of a [125I]BSA dose. Synthesis rate of tissue protein in biopsied rumen papillae was determined by measuring [13C...

  6. Tissue-Doppler assessment of cardiac left ventricular function during short-term adjuvant epirubicin therapy for breast cancer

    DEFF Research Database (Denmark)

    Appel, Jon M; Sogaard, Peter; Mortensen, Christiane E;

    2011-01-01

    It has been hypothesized that the extent of acute anthracycline-induced cardiotoxicity reflects the risk for late development of heart failure. The aim of this study was to examine if short-term changes in cardiac function can be detected even after low-dose adjuvant epirubicin therapy for breast...... cancer when using Doppler tissue imaging of longitudinal left ventricular function....

  7. Quantitative 3D breast magnetic resonance imaging fibroglandular tissue analysis and correlation with qualitative assessments: a feasibility study.

    Science.gov (United States)

    Ha, Richard; Mema, Eralda; Guo, Xiaotao; Mango, Victoria; Desperito, Elise; Ha, Jason; Wynn, Ralph; Zhao, Binsheng

    2016-04-01

    The amount of fibroglandular tissue (FGT) has been linked to breast cancer risk based on mammographic density studies. Currently, the qualitative assessment of FGT on mammogram (MG) and magnetic resonance imaging (MRI) is prone to intra and inter-observer variability. The purpose of this study is to develop an objective quantitative FGT measurement tool for breast MRI that could provide significant clinical value. An IRB approved study was performed. Sixty breast MRI cases with qualitative assessment of mammographic breast density and MRI FGT were randomly selected for quantitative analysis from routine breast MRIs performed at our institution from 1/2013 to 12/2014. Blinded to the qualitative data, whole breast and FGT contours were delineated on T1-weighted pre contrast sagittal images using an in-house, proprietary segmentation algorithm which combines the region-based active contours and a level set approach. FGT (%) was calculated by: [segmented volume of FGT (mm(3))/(segmented volume of whole breast (mm(3))] ×100. Statistical correlation analysis was performed between quantified FGT (%) on MRI and qualitative assessments of mammographic breast density and MRI FGT. There was a significant positive correlation between quantitative MRI FGT assessment and qualitative MRI FGT (r=0.809, n=60, Pqualitative MRI FGT assessment and mammographic density assessment (r=0.725, n=60, Pqualitative assessment categories of FGT correlated with the calculated mean quantitative FGT (%) of 4.61% (95% CI, 0-12.3%), 8.74% (7.3-10.2%), 18.1% (15.1-21.1%), 37.4% (29.5-45.3%). Quantitative measures of FGT (%) were computed with data derived from breast MRI and correlated significantly with conventional qualitative assessments. This quantitative technique may prove to be a valuable tool in clinical use by providing computer generated standardized measurements with limited intra or inter-observer variability.

  8. Randomized Trial of Pentoxifylline and Vitamin E vs Standard Follow-up After Breast Irradiation to Prevent Breast Fibrosis, Evaluated by Tissue Compliance Meter

    Energy Technology Data Exchange (ETDEWEB)

    Jacobson, Geraldine, E-mail: geraldine-jacobson@uiowa.edu [Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); Bhatia, Sudershan [Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); Smith, Brian J.; Button, Anna M. [Biostatistics Core, Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); Bodeker, Kellie; Buatti, John [Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States)

    2013-03-01

    Purpose: To conduct a randomized clinical trial to determine whether the combination of pentoxifylline (PTX) and vitamin E given for 6 months after breast/chest wall irradiation effectively prevents radiation-induced fibrosis (RIF). Methods and Materials: Fifty-three breast cancer patients with localized disease were enrolled and randomized to treatment with oral PTX 400 mg 3 times daily and oral vitamin E 400 IU daily for 6 months after radiation (n=26), or standard follow up (n=27). Tissue compliance meter (TCM) measurements were obtained at 18 months to compare tissue compliance in the irradiated and untreated breast/chest wall in treated subjects and controls. Measurements were obtained at 2 mirror image sites on each breast/chest wall, and the average difference in tissue compliance was scored. Differences in TCM measurements were compared using a t test. Subjects were followed a minimum of 2 years for local recurrence, disease-free survival, and overall survival. Results: The mean difference in TCM measurements in the 2 groups was 0.88 mm, median of 1.00 mm (treated) and 2.10 mm, median of 2.4 mm (untreated). The difference between the 2 groups was significant (P=.0478). Overall survival (100% treated, 90.6% controls at 5 years) and disease-free survival (96.2% treated, 86.8% controls at 5 years) were not significantly different in the 2 groups. Conclusions: This study of postirradiation breast cancer patients treated with PTX/vitamin E or standard follow-up indicated a significant difference in radiation-induced fibrosis as measured by TCM. There was no observed impact on local control or survival within the first 2 years of follow-up. The treatment was safe and well tolerated. Pentoxifylline/vitamin E may be clinically useful in preventing fibrosis after radiation in high-risk patients.

  9. Adipose tissue extracts plasma ammonia after sprint exercise in women and men.

    Science.gov (United States)

    Esbjörnsson, Mona; Bülow, Jens; Norman, Barbara; Simonsen, Lene; Nowak, Jacek; Rooyackers, Olav; Kaijser, Lennart; Jansson, Eva

    2006-12-01

    This study evaluates a possible contribution of adipose tissue to the elimination of plasma ammonia (NH(3)) after high-intensity sprint exercise. In 14 healthy men and women, repeated blood samples for plasma NH(3) analyses were obtained from brachial artery and from a subcutaneous abdominal vein before and after three repeated 30-s cycle sprints separated by 20 min of recovery. Biopsies from subcutaneous abdominal adipose tissue were obtained and analyzed for glutamine and glutamate content. After exercise, both arterial and abdominal venous plasma NH(3) concentrations were lower in women than in men (P women than in men (P sprint exercise (2.2 +/- 0.7 and 1.6 +/- 0.8, respectively) compared with the value at rest (1.2 +/- 0.6), suggesting a reaction of the extracted NH(3) with glutamate resulting in its conversion to glutamine. Adipose tissue may thus play an important physiological role in eliminating plasma NH(3) and thereby reducing the risk of NH(3) intoxication after high-intensity exercise.

  10. Three-dimensional imaging provides valuable clinical data to aid in unilateral tissue expander-implant breast reconstruction.

    Science.gov (United States)

    Tepper, Oren M; Karp, Nolan S; Small, Kevin; Unger, Jacob; Rudolph, Lauren; Pritchard, Ashley; Choi, Mihye

    2008-01-01

    The current approach to breast reconstruction remains largely subjective and is based on physical examination and visual-estimates of breast size. Thus, the overall success of breast reconstruction is limited by the inability of plastic surgeons to objectively assess breast volume and shape, which may result in suboptimal outcomes. A potential solution to this obstacle may be three-dimensional (3D) imaging, which can provide unique clinical data that was previously unattainable to plastic surgeons. The following study represents a prospective analysis of patient volunteers undergoing unilateral tissue expander (TE)-implant reconstruction by one of the two senior authors (MC, NSK). All patients underwent unilateral mastectomy with immediate or delayed insertion of a TE, followed by an exchange for a permanent silicone or saline implant. 3D scans were obtained during routine pre- and postoperative office visits. The 3D breast-volume calculations served as a guide for surgical management. Twelve patients have completed 3D-assisted unilateral breast reconstruction to date. These patients represent a wide range of body habitus and breast size/shape; 3D volume range from 136 to 518 cm(3). The mean baseline breast asymmetry in this group was 12.0 +/- 10.8%. Contralateral symmetry procedures were performed in eleven patients, consisting of the following: mastopexy (n = 6), augmentation (n = 1), mastopexy/augmentation (n = 2), and reduction mammoplasty (n = 2). Reconstruction was completed in a total number of 2 (n = 10) or 3 (n = 2) operations. Overall breast symmetry improved at the completion of reconstruction in the majority of patients, with an average postoperative symmetry of 95.1 +/- 4.4% (relative to 88% preoperatively). 3D imaging serves a valuable adjunct to TE-implant breast reconstruction. This technology provides volumetric data that can help guide breast reconstruction, such as in choosing the initial TE size, total volume of expansion, and final implant size

  11. SU-E-P-31: Quantifying the Amount of Missing Tissue in a Digital Breast Tomosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Goodenough, D [George Washington University, Washington, DC (United States); Olafsdottir, H; Olafsson, I; Fredriksson, J; Kristinsson, S; Oskarsdottir, G; Kristbjornsson, A [Raforninn Ehf., Reykjavik, Gullbringusysla (Iceland); Mallozzi, R; Healy, A; Levy, J [The Phantom Laboratory, Salem, NY (United States)

    2015-06-15

    Purpose: To automatically quantify the amount of missing tissue in a digital breast tomosynthesis system using four stair-stepped chest wall missing tissue gauges in the Tomophan™ from the Phantom Laboratory and image processing from Image Owl. Methods: The Tomophan™ phantom incorporates four stair-stepped missing tissue gauges by the chest wall, allowing measurement of missing chest wall in two different locations along the chest wall at two different heights. Each of the four gauges has 12 steps in 0.5 mm increments rising from the chest wall. An image processing algorithm was developed by Image Owl that first finds the two slices containing the steps then finds the signal through the highest step in all four gauges. Using the signal drop at the beginning of each gauge the distance to the end of the image gives the length of the missing tissue gauge in millimeters. Results: The Tomophan™ was imaged in digital breast tomosynthesis (DBT) systems from various vendors resulting in 46 cases used for testing. The results showed that on average 1.9 mm of 6 mm of the gauges are visible. A small focus group was asked to count the number of visible steps for each case which resulted in a good agreement between observer counts and computed data. Conclusion: First, the results indicate that the amount of missing chest wall can differ between vendors. Secondly it was shown that an automated method to estimate the amount of missing chest wall gauges agreed well with observer assessments. This finding indicates that consistency testing may be simplified using the Tomophan™ phantom and analysis by an automated image processing named Tomo QA. In general the reason for missing chest wall may be due to a function of the beam profile at the chest wall as DBT projects through the angular sampling. Research supported by Image Owl, Inc., The Phantom Laboratory, Inc. and Raforninn ehf; Mallozzi and Healy employed by The Phantom Laboratory, Inc.; Goodenough is a consultant to The

  12. The expression of syndecan-1, syndecan-4 and decorin in healthy human breast tissue during the menstrual cycle

    Directory of Open Access Journals (Sweden)

    Naessén Tord

    2010-04-01

    Full Text Available Abstract Background In order to unravel the interactions between the epithelium and the extra cellular matrix (ECM in breast tissue progressing to cancer, it is necessary to understand the relevant interactions in healthy tissue under normal physiologic settings. Proteoglycans in the ECM play an important role in the signaling between the different tissue compartments. The proteoglycan decorin is abundant in the breast stroma. Decreased expression in breast cancer tissue is a sign of a poor tumor prognosis. The heparane sulphate proteoglycans syndecan-1 and syndecan-4 promote the integration of cellular adhesion and proliferation. The aim of this study was to investigate the gene expression and location of decorin, syndecan-1 and syndecan-4 in the healthy breast during the menstrual cycle. Methods Tissue from healthy women undergoing breast reduction plastic surgery was examined using immunohistochemistry (n = 38 and Real-Time RT-PCR (n = 20. Both parous and nulliparous women were eligible and the mean age of the women was 34(+/- 10 years with regular menstrual cycles (28 +/- 7 days. None of the women had used hormonal treatment the last three months. The women were randomized to needle biopsy two months before the operation in the follicular or luteal menstrual phase and for another biopsy at the operation in the opposite phase. Serum samples were obtained to characterize the menstrual phase. The Wilcoxon signed rank test and Mann Whitney test were used for statistical analyses. Results By real time-RT-PCR the gene signal for all three proteoglycans; decorin (p = 0.02 and syndecan-1 (p = 0.03 and syndecan-4 (p = 0.02 was significantly lower among parous women in the luteal phase than in the follicular phase. Immunohistochemistry confirmed the identification of the proteins but no significant difference between menstrual phases was observed. Serum samples verified the menstrual phase. Conclusions Our study shows, for the first time in the

  13. Effects of n-3 PUFAs on breast cancer cells through their incorporation in plasma membrane

    Directory of Open Access Journals (Sweden)

    Berra Bruno

    2011-05-01

    Full Text Available Abstract Background PUFAs are important molecules for membrane order and function; they can modify inflammation-inducible cytokines production, eicosanoid production, plasma triacylglycerol synthesis and gene expression. Recent studies suggest that n-3 PUFAs can be cancer chemopreventive, chemosuppressive and auxiliary agents for cancer therapy. N-3 PUFAs could alter cancer growth influencing cell replication, cell cycle, and cell death. The question that remains to be answered is how n-3 PUFAs can affect so many physiological processes. We hypothesize that n-3 PUFAs alter membrane stability, modifying cellular signalling in breast cancer cells. Methods Two lines of human breast cancer cells characterized by different expression of ER and EGFR receptors were treated with AA, EPA or DHA. We have used the MTT viability test and expression of apoptotic markers to evaluate the effect of PUFAs on cancer growth. Phospholipids were analysed by HPLC/GC, to assess n-3 incorporation into the cell membrane. Results We have observed that EPA and DHA induce cell apoptosis, a reduction of cell viability and the expression of Bcl2 and procaspase-8. Moreover, DHA slightly reduces the concentration of EGFR but EPA has no effect. Both EPA and DHA reduce the activation of EGFR. N-3 fatty acids are partially metabolized in both cell lines; AA is integrated without being further metabolized. We have analysed the fatty acid pattern in membrane phospholipids where they are incorporated with different degrees of specificity. N-3 PUFAs influence the n-6 content and vice versa. Conclusions Our results indicate that n-3 PUFA feeding might induce modifications of breast cancer membrane structure that increases the degree of fatty acid unsaturation. This paper underlines the importance of nutritional factors on health maintenance and on disease prevention.

  14. Characterization of Cystic Breast Masses on Ultrasound: Comparative Study among Conventional, Tissue Harmonic, Compound, and a Combination of Tissue Harmonic and Compound Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Choo, Ji Yung; Seo, Bo Kyoung; Yi, Ann; Cho, Kyu Ran; Son, Gil Soo; Kim, Baek Hyun [Korea University Ansan Hospital, Korea University College of Medicine, Ansan (Korea, Republic of); Kim, Hee Young [Institute of Economics, Korea University, Seoul (Korea, Republic of); Woo, Ok Hee [Korea University Guro Hospital, Korea University College of Medicine, Seoul (Korea, Republic of)

    2010-12-15

    This prospective study was to compare the image quality and diagnostic performance of breast cystic masses by conventional and advanced ultrasound (US) techniques including tissue harmonic, compound, and the combination of these techniques. All 91 patients, collectively having 109 breast cystic masses were scanned using four US techniques (complicated cysts in 36, septated cysts in 33, and complex cysts in 40). Two breast radiologists independently assessed the image quality and possibility of malignancy. Image quality was evaluated in terms of contrast and clarity of the wall and internal echo pattern and then graded on a scale of 1 (poor) to grade 3 (satisfactory). The possibility of malignancy was graded on a scale of 1 (suggestive of benignancy) to 5 (suggestive of malignancy) using US images. The histopathological results and follow-up images were used as the reference standard for the assessment of diagnostic performance. Results were evaluated by Friedman's test and receiver operating characteristic (ROC) analyses. In terms of image quality, a grade of 3 was significantly more frequent in the three advanced US techniques than conventional US (p < 0.05). For assessment of diagnostic performance, areas under the ROC curves in three advanced techniques were significantly higher than in conventional US (p < 0.05). Advanced US techniques including compound and tissue harmonic US techniques provide a better image quality in breast cystic masses and also improve the diagnostic performance compared with conventional US

  15. Accuracy of fully automated, quantitative, volumetric measurement of the amount of fibroglandular breast tissue using MRI: correlation with anthropomorphic breast phantoms.

    Science.gov (United States)

    Wengert, Georg J; Pinker, Katja; Helbich, Thomas H; Vogl, Wolf-Dieter; Spijker, Sylvia M; Bickel, Hubert; Polanec, Stephan H; Baltzer, Pascal A

    2017-06-01

    To demonstrate the accuracy of fully automated, quantitative, volumetric measurement of the amount of fibroglandular breast tissue (FGT), using MRI, and to investigate the impact of different MRI sequences using anthropomorphic breast phantoms as the ground truth. In this study, 10 anthropomorphic breast phantoms that consisted of different known fractions of adipose and protein tissue, which closely resembled normal breast parenchyma, were developed. Anthropomorphic breast phantoms were imaged with a 1.5 T unit (Siemens, Avantofit) using an 18-channel breast coil. The sequence protocol consisted of an isotropic Dixon sequence (Di), an anisotropic Dixon sequence (Da), and T1 3D FLASH sequences with and without fat saturation (T1). Fully automated, quantitative, volumetric measurement of FGT for all anthropomorphic phantoms and sequences was performed and correlated with the amounts of fatty and protein components in the phantoms as the ground truth. Fully automated, quantitative, volumetric measurements of FGT with MRI for all sequences ranged from 5.86 to 61.05% (mean 33.36%). The isotropic Dixon sequence yielded the highest accuracy (median 0.51%-0.78%) and precision (median range 0.19%) compared with anisotropic Dixon (median 1.92%-2.09%; median range 0.55%) and T1 -weighted sequences (median 2.54%-2.46%; median range 0.82%). All sequences yielded good correlation with the FGT content of the anthropomorphic phantoms. The best correlation of FGT measurements was identified for Dixon sequences (Di, R(2)  = 0.999; Da, R(2)  = 0.998) compared with conventional T1 -weighted sequences (R(2)  = 0.971). MRI yields accurate, fully automated, quantitative, volumetric measurements of FGT, an increasingly important and sensitive imaging biomarker for breast cancer risk. Compared with conventional T1 sequences, Dixon-type sequences show the highest correlation and reproducibility for automated, quantitative, volumetric FGT measurements using anthropomorphic breast

  16. Dynamic modeling of breast tissue with application of model reference adaptive system identification technique based on clinical robot-assisted palpation.

    Science.gov (United States)

    Keshavarz, M; Mojra, A

    2015-11-01

    Accurate identification of breast tissue's dynamic behavior in physical examination is critical to successful diagnosis and treatment. In this study a model reference adaptive system identification (MRAS) algorithm is utilized to estimate the dynamic behavior of breast tissue from mechanical stress-strain datasets. A robot-assisted device (Robo-Tac-BMI) is going to mimic physical palpation on a 45 year old woman having a benign mass in the left breast. Stress-strain datasets will be collected over 14 regions of both breasts in a specific period of time. Then, a 2nd order linear model is adapted to the experimental datasets. It was confirmed that a unique dynamic model with maximum error about 0.89% is descriptive of the breast tissue behavior meanwhile mass detection may be achieved by 56.1% difference from the normal tissue.

  17. An investigation of plasma and salivary oxytocin responses in breast- and formula-feeding mothers of infants.

    Science.gov (United States)

    Grewen, Karen M; Davenport, Russell E; Light, Kathleen C

    2010-07-01

    Oxytocin (OT) is a peptide increasingly studied in relation to human social interactions, affiliation, and clinical disorders. Studies are constrained by use of invasive blood draws and would benefit from a reliable salivary OT assay. Our goals were to examine feasibility of salivary OT measurement, compare salivary to plasma OT responses in 12 breast- and 8 formula-feeding mothers, and assess the degree of correlation between plasma and salivary OT. Using a commercial EIA kit, we measured OT in 5 saliva and 7 plasma samples in a protocol designed to elicit changes in OT (Rest, Infant Interaction, Stress, Feeding). Breast-feeders had higher OT levels than formula-feeders across all conditions in plasma (+36%) and saliva (+23%). OT levels and ranges were similar in saliva and plasma, with slightly greater variance in saliva. Concurrently sampled plasma and salivary OT were correlated at end of Baseline Rest (r=+.59, p=.022) and Post-Stress Recovery (r=+.59, p=.025). These data suggest that salivary OT assay is feasible, and will be of value where plasma samples are not possible. Validation with larger samples is needed.

  18. Do we have to consider chemotherapy in the analysis of association between OCs in breast adipose tissue and the risk of female breast cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Strucinski, P.; Wojtyniak, B.; Goralczyk, K.; Czaja, K.; Hernik, A.; Ludwicki, J.K. [National Inst. of Hygiene, Warsaw (Poland); Baranska, J.; Olszewski, W.T. [Maria Sklodowska-Curie Inst. of Oncology, Warsaw (Poland)

    2004-09-15

    The purpose of this study was to investigate whether adipose tissue levels of selected persistent organochlorine pollutants might be associated with chemotherapy in women with breast cancer. A total of 165 samples, of mammary gland's adipose tissue taken from breast cancer women, obtained from Maria Sklodowska-Curie Institute of Oncology in Warsaw, were assayed. The donors had been divided into two subgroups - first, treated shortly before mastectomy with preoperative induction chemotherapy (used in case of locally advanced, primary inoperable breast cancers) and neoadjuvant chemotherapy (given to prevent metastases or spread the disease beyond the primary tumour), consisting of 29 patients, and second, including 136 untreated patients. The identification and quantification of compounds analyzed: HCB, {beta}a-HCH, p,p'-DDT, p,p'- DDD, p,p'-DDE, and {sigma}OPCBs (calculated as Aroclor 1254) in adipose tissue samples was performed in the Department of Environmental Toxicology of the National Institute of Hygiene in Warsaw. The analytical procedure included analyte extraction with n-hexane, and clean-up with concentrated sulfuric acid. Finally, the analysis was carried out by gas chromatography with electron capture detector with ion-trap mass spectrometric confirmation.

  19. Epigenetic induction of tissue inhibitor of matrix metalloproteinase-3 by green tea polyphenols in breast cancer cells.

    Science.gov (United States)

    Deb, Gauri; Thakur, Vijay S; Limaye, Anil M; Gupta, Sanjay

    2015-06-01

    Aberrant epigenetic silencing of the tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) gene that negatively regulates matrix metalloproteinases (MMPs) activity has been implicated in the pathogenesis and metastasis of breast cancer. In the present study, we demonstrate that green tea polyphenols (GTP) and its major constituent, epigallocatechin-3-gallate (EGCG) mediate epigenetic induction of TIMP-3 levels and play a key role in suppressing invasiveness and gelatinolytic activity of MMP-2 and MMP-9 in breast cancer cells. Treatment of MCF-7 and MDA-MB-231 breast cancer cells with 20 µM EGCG and 10 µg/mL GTP for 72 h significantly induces TIMP-3 mRNA and protein levels. Interestingly, investigations into the molecular mechanism revealed that TIMP-3 repression in breast cancer cells is mediated by epigenetic silencing mechanism(s) involving increased activity of the enhancer of zeste homolog 2 (EZH2) and class I histone deacetylases (HDACs), independent of promoter DNA hypermethylation. Treatment of breast cancer cells with GTP and EGCG significantly reduced EZH2 and class I HDAC protein levels. Furthermore, transcriptional activation of TIMP-3 was found to be associated with decreased EZH2 localization and H3K27 trimethylation enrichment at the TIMP-3 promoter with a concomitant increase in histone H3K9/18 acetylation. Our findings highlight TIMP-3 induction as a key epigenetic event modulated by GTPs in restoring the MMP:TIMP balance to delay breast cancer progression and invasion.

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

    Science.gov (United States)

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

    2013-07-01

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

  1. Semi-automatic identification of punching areas for tissue microarray building: the tubular breast cancer pilot study

    Directory of Open Access Journals (Sweden)

    Beltrame Francesco

    2010-11-01

    Full Text Available Abstract Background Tissue MicroArray technology aims to perform immunohistochemical staining on hundreds of different tissue samples simultaneously. It allows faster analysis, considerably reducing costs incurred in staining. A time consuming phase of the methodology is the selection of tissue areas within paraffin blocks: no utilities have been developed for the identification of areas to be punched from the donor block and assembled in the recipient block. Results The presented work supports, in the specific case of a primary subtype of breast cancer (tubular breast cancer, the semi-automatic discrimination and localization between normal and pathological regions within the tissues. The diagnosis is performed by analysing specific morphological features of the sample such as the absence of a double layer of cells around the lumen and the decay of a regular glands-and-lobules structure. These features are analysed using an algorithm which performs the extraction of morphological parameters from images and compares them to experimentally validated threshold values. Results are satisfactory since in most of the cases the automatic diagnosis matches the response of the pathologists. In particular, on a total of 1296 sub-images showing normal and pathological areas of breast specimens, algorithm accuracy, sensitivity and specificity are respectively 89%, 84% and 94%. Conclusions The proposed work is a first attempt to demonstrate that automation in the Tissue MicroArray field is feasible and it can represent an important tool for scientists to cope with this high-throughput technique.

  2. Expression and Clinical Significance of Vascular Endothelial Growth Factor in Benign and Malignant Tissues of Breast

    Institute of Scientific and Technical Information of China (English)

    XU Wei-gu; LIU Yang; WANG Gang; SONG Ji-ning; YANG Xiao-qing; WANG Wen-ya

    2008-01-01

    Objective:To detect the expression of vascular endothelial growth factor(VEGF)and microvessel density(MVD)count in breast benign affection,breast atypical hyperplasia and breast carcinoma in situ,and to clarify the relationship between VEGF expression,MVD and the clinicopathological features of these diseases. Methods:The expression of VEGF and MVD count in 115 cases breast benign diseases(including 40 breast fibroid tumor,40 breast cystic hyperplasia and 35 intraductal papilloma,19 breast atypical hyperplasias and 32 breast carcinomas in situ were examined by immunohistochemistry staining(SP-method). Results:The positive rate of VEGF in breast benign diseases,breast atypical hyperplasia and breast carcinoma in situ were 21.74%(25/115)、31.58.%(6/19)and 53.13%(17/32)respectively.It was the lowest in breast benign affection group,and was the highest breast carcinoma in situ group.The expression of VEGF increased gradually in the three groups(P<0.05).The MVD count of the three groups were 14.41±2.59,18.89±4.47 and 21.13±4.12 respectively,It was the lowest in breast benign affection group,and was the highest breast carcinoma in situ group.The MVD count of the three groups increased gradually(P<0.05).In VEGF positive group,MVD count was 19.41±4.78;In VEGF negative group,MVD count was 14.91±3.15.The MVD count was higher in VEGF positive group than that in VEGF negative group(P<0.05). Conclusion:The results of this study suggested that VEGF could promote microvessel growth in breast tumors.The occurrence and progression of breast cancer might be related with the expression of VEGF.

  3. Determination of piroxicam from rat articular tissue and plasma based on LC-MS/MS.

    Science.gov (United States)

    Kim, Han Sol; Cho, Ha Ra; Ho, Myoung Jin; Kang, Myung Joo; Choi, Yong Seok

    2016-12-01

    Osteoarthritis (OA) is the most common type of arthritis. To manage OA, in general, oral administration of non-steroidal anti-inflammatory drugs (NSAIDs) is used. Recently, the analgesic and anti-inflammatory efficacy of piroxicam (PX), a long-acting NSAID, by intra-articular (IA) administration in OA was reported, and the possibility that PX is distributed in articular tissues at a certain concentration was raised. Thus, herein, novel LC-MS/MS methods to detect PX in rat articular tissue and plasma are presented. For articular tissue, solvent extraction with acetonitrile for 12 h was employed and a protein precipitation method was used for the preparation of a plasma sample. The developed methods were validated by following the FDA guidelines, and the validated methods were successfully applied to a PK study of IA PX. The present study presents, to our knowledge, the first method of determining a drug in articular tissue. Additionally, the level of PX in articular tissue after IA PX administration was experimentally confirmed for the first time using the present methods. Therefore, the present methods provide a new direction for in vivo evaluation for IA PX formulations and contribute to the development of alternative IA PX formulations with better effects for the treatment of OA.

  4. Tissue expression and plasma levels of adrenomedullin in renal cancer patients

    DEFF Research Database (Denmark)

    Michelsen, Jens; Thiesson, Helle; Walter, Steen;

    2006-01-01

    The peptide AM (adrenomedullin) is stimulated by hypoxia through HIF-1 (hypoxia-inducible factor-1). The majority of human CC-RCCs (clear cell renal cell carcinomas) display mutations in the tumour suppressor protein von Hippel-Lindau, which leads to constitutively elevated HIF-1. We hypothesized......RNA and peptide expression in tissue and AM plasma concentration were determined. HIF-1alpha was localized in tissue by immunohistochemistry. AM mRNA was elevated in CC-RCC compared with adjacent renal cortex (6-fold, n=18; P

  5. STUDY OF ECK GENE EXON-3 FROM HUMAN NORMAL TISSUE AND BREAST CANCER CELL LINE

    Institute of Scientific and Technical Information of China (English)

    李瑶琛; 孔令洪; 王一理; 司履生

    2003-01-01

    Objective To establish a method cloning the exon 3 of eck gene from normal tissue and ZR-75-1 cell line (a human breast cancer cell line)and study whether these genes exist mutant. Methods Designed a pair of specific primers and amplified the exon 3 of eck gene fragment from the extracted genomic DNA derived from normal epithelial cells from skin tissue and ZR-75-1 cell line respectively by PCR technique. Transformed the E.coil. JM109 with recombinant plamids constructed by inserting the amplified fragments into medium vector pUCm-T and sequenced these amplified fragments after primary screening of endonuclease restriction digestion and PCR amplification. Results ① Obtained the genomic DNA of human normal epithelial cells and ZR-75-1 cell line respectively. ② Obtained the amplified fragments of human exon 3 of eck gene through PCR technique. ③ Obtained the cloning vectors of exon 3 of eck gene of human normal epithelial cells and ZR-75-1 cell line respectively. ④ ZR-75-1 cell line exists mutation of nucleotides. Conclusion Successfully established the method of cloning the human exon 3 of eck gene and found some mutations in the detected samples. This study lays a foundation for further studying the function of eck gene in tumorgenesis.

  6. Targeted MS Assay Predicting Tamoxifen Resistance in Estrogen-Receptor-Positive Breast Cancer Tissues and Sera.

    Science.gov (United States)

    De Marchi, Tommaso; Kuhn, Erik; Dekker, Lennard J; Stingl, Christoph; Braakman, Rene B H; Opdam, Mark; Linn, Sabine C; Sweep, Fred C G J; Span, Paul N; Luider, Theo M; Foekens, John A; Martens, John W M; Carr, Steven A; Umar, Arzu

    2016-04-01

    We recently reported on the development of a 4-protein-based classifier (PDCD4, CGN, G3BP2, and OCIAD1) capable of predicting outcome to tamoxifen treatment in recurrent, estrogen-receptor-positive breast cancer based on high-resolution MS data. A precise and high-throughput assay to measure these proteins in a multiplexed, targeted fashion would be favorable to measure large numbers of patient samples to move these findings toward a clinical setting. By coupling immunoprecipitation to multiple reaction monitoring (MRM) MS and stable isotope dilution, we developed a high-precision assay to measure the 4-protein signature in 38 primary breast cancer whole tissue lysates (WTLs). Furthermore, we evaluated the presence and patient stratification capabilities of our signature in an independent set of 24 matched (pre- and post-therapy) sera. We compared the performance of immuno-MRM (iMRM) with direct MRM in the absence of fractionation and shotgun proteomics in combination with label-free quantification (LFQ) on both WTL and laser capture microdissected (LCM) tissues. Measurement of the 4-proteins by iMRM showed not only higher accuracy in measuring proteotypic peptides (Spearman r: 0.74 to 0.93) when compared with MRM (Spearman r: 0.0 to 0.76) but also significantly discriminated patient groups based on treatment outcome (hazard ratio [HR]: 10.96; 95% confidence interval [CI]: 4.33 to 27.76; Log-rank P < 0.001) when compared with LCM (HR: 2.85; 95% CI: 1.24 to 6.54; Log-rank P = 0.013) and WTL (HR: 1.16; 95% CI: 0.57 to 2.33; Log-rank P = 0.680) LFQ-based predictors. Serum sample analysis by iMRM confirmed the detection of the four proteins in these samples. We hereby report that iMRM outperformed regular MRM, confirmed our previous high-resolution MS results in tumor tissues, and has shown that the 4-protein signature is measurable in serum samples.

  7. Na+,HCO3--cotransport is functionally upregulated during human breast carcinogenesis and required for the inverted pH gradient across the plasma membrane

    DEFF Research Database (Denmark)

    Lee, Soojung; Mele, Marco; Vahl, Pernille

    2015-01-01

    and promoting cancer cell metabolism, proliferation, migration, and invasion. We investigated the effects of breast carcinogenesis on the mechanisms of cellular pH control using multicellular epithelial organoids freshly isolated from human primary breast carcinomas and matched normal breast tissue...... (~0.3 units of magnitude) in steady-state intracellular pH of human primary breast carcinomas compared to normal breast tissue. Na(+)/H(+)-exchange activity and steady-state intracellular pH in the absence of CO2/HCO3 (-) were practically unaffected by breast carcinogenesis. These effects were evident....... Intracellular pH was measured by fluorescence microscopy, while protein expression was investigated by immunofluorescence imaging and immunoblotting. We found that cellular net acid extrusion increased during human breast carcinogenesis due to enhanced Na(+),HCO3 (-)-cotransport, which created an alkaline shift...

  8. [Tyrosine-protein kinase activity in breast neoplasm. Comparison with activity obtained in benign diseases and in normal tissues].

    Science.gov (United States)

    Pierart, J; Oñate, E; Klaassen, R; Cid, L; Gutierrez, S; Talbot, E; Ross, E; Zambrano, C; Burmeister, R; Puchi, M

    1995-02-01

    Tyrosine protein kinase (TPK) activity is associated to malignant cellular transformation. This work compares TPK activity in 27 surgical biopsy samples of mammary carcinoma, 10 samples of fibroadenomas, 13 samples of fibrocystic breast disease and 27 samples of normal mammary tissue. TPK activity was determined in tissue homogenates using (Val5) angiotensin II as exogenous substrate. In samples of mammary carcinoma, TPK activity was 33.86 +/- 31.98 pmol P32/mg protein/30 min. This value was significantly higher that those observed in fibrocystic disease (3.92 +/- 2.35), fibroadenomas (13.86 +/- 10.9) and normal tissue (3.56 +/- 3.02).

  9. LH receptor gene expression is essentially absent in breast tumor tissue: Implications for treatment

    NARCIS (Netherlands)

    T.M. Kuijper (Martijn); K. Ruigrok-Ritstier (Kirsten); M. Verhoef-Post (Miriam); D. Piersma (Djura); M.W.P. Bruysters (Martijn); P.M.J.J. Berns (Els); A.P.N. Themmen (Axel)

    2009-01-01

    textabstractWorldwide, breast cancer is the most frequently occurring malignancy in women. Early age at full term pregnancy has a protective effect against breast cancer. Evidence coming from a rat breast cancer model suggests a possible role for the pregnancy hormone hCG, a ligand of the LH recepto

  10. Detrimental effects of fluvastatin on plasma lipid metabolism in rat breast carcinoma model

    Directory of Open Access Journals (Sweden)

    Kapinová Andrea

    2013-01-01

    Full Text Available From clinical practice, obvious positive effects of statins on plasma lipid metabolism are well known. On the other hand, there are several experimental rodent studies, where these beneficial effects were not confirmed. The effects of fluvastatin on selected serum lipid parameters in a rat model of experimental breast cancer were determined. The drug was dietary administered at two concentrations of 20 and 200 mg/kg. At the end of the study (experiment duration - 18 weeks the blood from each animal was collected and serum lipid parameters were evaluated. Fluvastatin in both treated groups significantly increased parameters of serum lipids (mostly in a dose dependent manner. Fluvastatin in both treated groups of animals significantly increased serum levels of triacylglycerols, total cholesterol, and LDL-, HDL-, VLDL-cholesterol when compared to the control group. Our results pointed out to the apparent harmful effects of fluvastatin on plasma lipid metabolism in rat mammary carcinogenesis. Based on our previous results, it seems that rats commonly used in cancer model studies are generally unresponsive to the hypocholesterolemic effects of statins.

  11. Direct detection of herceptin/trastuzumab binding on breast tissue sections.

    Science.gov (United States)

    Glazyrin, Alexey; Shen, Xiaoyun; Blanc, Victoria; Eliason, James F

    2007-01-01

    The protooncogene product HER-2/neu is the target of the humanized monoclonal antibody trastuzumab (Herceptin). Several tests are used clinically to identify patients with HER-2/neu overexpression based on evaluation by pathologists of gene amplification by fluorescence in situ hybridization or protein expression using immunohistochemistry (IHC). A simple technique has been developed for staining formalin-fixed, paraffin-embedded breast cancer tissue using unmodified Herceptin/trastuzumab as the primary antibody. Results were compared with staining with the commercial kit, HercepTest, as well as with polyclonal anti-HER-2/neu antibodies and with biotinylated trastuzumab. These procedures were tested using four breast cancer microarrays. There were 854 cores that were stained with all four antibodies, representing 325 cases. A standard 4-point scoring system (0-3) was used. A total of 156 cases (48%) were scored as 0 by all the methods used and 31 (9.5%) were positive (3+) by all methods. Of interest, three cases scored negative using polyclonal anti-HER-2/neu antibodies but were positive using unmodified trastuzumab. To clarify this discrepancy, whole sections of tumors were examined with both antibodies using double labeling. There were some tumors that demonstrated a mosaic pattern of staining with neighboring cells or groups of cells stained exclusively with one antibody or the other. These results demonstrate that unmodified humanized or human therapeutic antibodies could be used for preclinical testing or in a clinical laboratory setting for IHC-based selection of patients for treatment, and results of such selection could be different from those obtained using polyclonal antibody-based IHC procedure.

  12. Failure rate and cosmesis of immediate tissue expander/implant breast reconstruction after postmastectomy irradiation.

    Science.gov (United States)

    Baschnagel, Andrew M; Shah, Chirag; Wilkinson, J Ben; Dekhne, Nayana; Arthur, Douglas W; Vicini, Frank A

    2012-12-01

    This study reports the rate of breast reconstruction failure and cosmetic outcomes after postmastectomy radiation therapy (PMRT) with temporary tissue expanders (TEs) or implants in place. Ninety-four patients underwent mastectomy (93 unilateral, 1 bilateral; 95 cases total) and immediate TE reconstruction followed by PMRT. Ninety TEs and 5 permanent implants were irradiated. All patients received a dose of 5400 cGy given in 180-cGy fractions to the reconstructed breast. Twenty-one patients (22%) received tangents alone and 74 patients (78%) were treated with tangents and a supraclavicular field using a monoisocentric technique. Bolus was used in 91 patients (96%). Eighty-eight patients (93%) received chemotherapy and 78 patients (82%) received endocrine therapy. With a median follow-up of 24.1 months, 19 patients (20%) experienced failure of reconstruction. The 1-, 2-, and 3-year actuarial rate of reconstruction failure was 9.7%, 19.3%, and 25.5%, respectively. Infection was the most common cause of failure. Of the 19 failures, 8 patients underwent salvage procedures with flap reconstruction. Univariate analysis was performed examining age, chemotherapy use, hormone therapy use, use of a supraclavicular field, smoking status, diabetes, hypertension, and menopausal status. No risk factors were found to be associated with reconstruction failure. In patients who did not experience reconstruction failure, good/excellent cosmesis was observed in 75% of patients. In the current series of women with a high risk of locoregional recurrence, PMRT with a TE/implant in place provides good cosmesis in the majority of women, with an acceptable risk of expander or implant loss. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Expression of connective tissue growth factor in male breast cancer: clinicopathologic correlations and prognostic value.

    Directory of Open Access Journals (Sweden)

    Miangela M Lacle

    Full Text Available Connective tissue growth factor (CTGF/CCN2 is a member of the CCN family of secreted proteins that are believed to play an important role in the development of neoplasia. In particular, CTGF has been reported to play an important role in mammary tumorigenesis and to have prognostic value in female breast cancer (FBC. The aim of the present study was to investigate clinicopathologic correlations and prognostic value of CTGF in male breast cancer (MBC and to compare these findings with FBC. For this, we studied CTGF protein expression by immunohistochemistry in 109 MBC cases and 75 FBC cases. In MBC, stromal CTGF expression was seen in the majority of the cases 78% (85/109 with high expression in 31/109 cases (28.4%, but expression in tumor cells was only seen in 9.2% (10/109 of cases. High stromal CTGF expression correlated with high grade and high proliferation index (>15% assessed by MIB-1 immunohistochemical staining. CTGF expression in tumor epithelial cells did not correlate with any of the clinicopathologic features. In FBC, stromal CTGF expression positively correlated with mitotic count and tumor CTGF expression was associated with triple negative status of the tumor (p = 0.002. Neither stromal nor tumor epithelial cell CTGF expression had prognostic value in MBC and FBC. In conclusion, stromal CTGF expression was seen in a high percentage of MBC and was correlated with high grade and high proliferation index. In view of the important role of the microenvironment in cancer progression, this might suggest that stromal CTGF could be an interesting target for novel therapies and molecular imaging. However, the lack of association with prognosis warrants caution. The potential role of CTGF as a therapeutic target for triple negative FBC deserves to be further studied.

  14. Classification of breast tissue using a laboratory system for small-angle x-ray scattering (SAXS).

    Science.gov (United States)

    Sidhu, S; Falzon, G; Hart, S A; Fox, J G; Lewis, R A; Siu, K K W

    2011-11-07

    Structural changes in breast tissue at the nanometre scale have been shown to differentiate between tissue types using synchrotron SAXS techniques. Classification of breast tissues using information acquired from a laboratory SAXS camera source could possibly provide a means of adopting SAXS as a viable diagnostic procedure. Tissue samples were obtained from surgical waste from 66 patients and structural components of the tissues were examined between q = 0.25 and 2.3 nm(-1). Principal component analysis showed that the amplitude of the fifth-order axial Bragg peak, the magnitude of the integrated intensity and the full-width at half-maximum of the fat peak were significantly different between tissue types. A discriminant analysis showed that excellent classification can be achieved; however, only 30% of the tissue samples provided the 16 variables required for classification. This suggests that the presence of disease is represented by a combination of factors, rather than one specific trait. A closer examination of the amorphous scattering intensity showed not only a trend of increased scattering intensity with disease severity, but also a corresponding decrease in the size of the scatterers contributing to this intensity.

  15. Classification of breast tissue using a laboratory system for small-angle x-ray scattering (SAXS)

    Science.gov (United States)

    Sidhu, S.; Falzon, G.; Hart, S. A.; Fox, J. G.; Lewis, R. A.; Siu, K. K. W.

    2011-11-01

    Structural changes in breast tissue at the nanometre scale have been shown to differentiate between tissue types using synchrotron SAXS techniques. Classification of breast tissues using information acquired from a laboratory SAXS camera source could possibly provide a means of adopting SAXS as a viable diagnostic procedure. Tissue samples were obtained from surgical waste from 66 patients and structural components of the tissues were examined between q = 0.25 and 2.3 nm-1. Principal component analysis showed that the amplitude of the fifth-order axial Bragg peak, the magnitude of the integrated intensity and the full-width at half-maximum of the fat peak were significantly different between tissue types. A discriminant analysis showed that excellent classification can be achieved; however, only 30% of the tissue samples provided the 16 variables required for classification. This suggests that the presence of disease is represented by a combination of factors, rather than one specific trait. A closer examination of the amorphous scattering intensity showed not only a trend of increased scattering intensity with disease severity, but also a corresponding decrease in the size of the scatterers contributing to this intensity.

  16. Plasma Tissue Factor Pathway Inhibitor Levels in Angiographically Defined Coronary Artery Disease Among Saudis

    Directory of Open Access Journals (Sweden)

    Syed Shahid Habib

    2013-05-01

    Full Text Available Objectives: This study was aimed to determine plasma levels of total (TFPI-T and free (TFPI-F tissue factor pathway inhibitor, plasminogen activator inhibitor-1 (PAI-1, and tissue plasminogen activator (t-PA in a cohort of Saudi patients with chronic stable angiographically defined coronary artery disease (CAD and to determine its correlation with its severity.Methods: This cross sectional study was conducted in the department of physiology and department of cardiology, College of Medicine, and King Khalid University Hospital and King Saud University, Riyadh. Sixty known cases of CAD who had undergone angiography (35 males and 25 females were selected. A control group included 39 (20 males and 19 females healthy subjects. Fasting venous blood samples were analyzed for total (TFPI-T and free (TFPI-F tissue factor pathway inhibitor, plasminogen activator inhibitor-1 (PAI-1, and tissue plasminogen activator (t-PA. Gensini scores and vessel scores were determined for assessing CAD severity.Results: There were non-significant differences between age, body mass index (BMI and Blood pressure between the controls and CAD subjects. A comparison of hemostatic markers between control and CAD patients showed significantly higher levels of Fibrinogen, PAI-1, TFPI-T and TFPI-F in CAD patients compared to control subjects. But there was no difference in plasma t-PA levels. TFPI-T had a significant positive correlation with severity of disease determined by Gensini Scores (r=0.344; p=0.006 and vessel scores (r=0.338; p=0.015.Conclusion: Plasma levels of total tissue factor pathway inhibitor are significantly related with the presence and severity of CAD. Elevated levels of TFPI-T may be considered as useful diagnostic and prognostic markers in patients with CAD.

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

    Science.gov (United States)

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

    2014-11-01

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

  18. Association between tumor tissue TIMP-1 levels and objective response to first-line chemotherapy in metastatic breast cancer

    DEFF Research Database (Denmark)

    Klintman, Marie; Würtz, Sidse Ørnbjerg; Christensen, Ib Jarle;

    2010-01-01

    In a previous study from our laboratory, high tumor levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) have been associated with an adverse response to chemotherapy in metastatic breast cancer suggesting that TIMP-1, which is known to inhibit apoptosis, may be a new predictive marker...... in this disease. The purpose of this study was to investigate the association between TIMP-1 and objective response to chemotherapy in an independent patient population consisting of patients with metastatic breast cancer from Sweden and Denmark. TIMP-1 was measured using ELISA in 162 primary tumor extracts from...... patients who later developed metastatic breast cancer and these levels were related to the objective response to first-line chemotherapy. Increasing levels of TIMP-1 were associated with a decreasing probability of response to treatment, reaching borderline significance (OR = 1.59, 95% CI: 0.97-2.62, P = 0...

  19. Content of alpha-linolenic acid in human atrial tissue correlates with plasma levels of alpha-linolenic acid

    DEFF Research Database (Denmark)

    Gu, Jiwei; Eschen, Rikke Bülow; Andreasen, Annette

    and ALA levels were compared by the Pearson correlation coefficient. Results: There was a statistical significant correlation (r=0.54, 95% confidence interval: 0.30-0.71) between levels of ALA in plasma phospholipids and atrial tissue. Conclusion: The content of ALA in plasma phospholipids is a short term...... indicator of intake of ALA and this correlated well with the content of ALA in atrial tissue. Atrial tissue is not readily available but this study shows that determination of plasma phospholipids may be useful to further investigate an antiarrhythmic effect of ALA on AF....

  20. Human breast adipose‑derived stem cells: characterization and differentiation into mammary gland‑like epithelial cells promoted by autologous activated platelet‑rich plasma.

    Science.gov (United States)

    Cui, Shi-En; Li, Hong-Mian; Liu, Da-Lie; Nan, Hua; Xu, Kun-Ming; Zhao, Pei-Ran; Liang, Shuang-Wu

    2014-08-01

    Human adipose‑derived stem cells (ASCs) isolated from various body sites have been widely investigated in basic and clinical studies. However, ASCs derived from human breast tissue (hbASCs) have not been extensively investigated. In order to expand our understanding of hbASCs and examine their potential applications in stem cell research and cell‑based therapy, hbASCs were isolated from discarded surgical fat tissue following reduction mammoplasty and a comprehensive characterization of these hbASCs was performed, including analysis of their cellular morphology, growth features, cell surface protein markers and multilineage differentiation capacity. These hbASCs expressed cluster of differentiation (CD)44, CD49d, CD90 and CD105, but did not express CD31 and CD34. Subsequently, the hbASCs were differentiated into adipocytes, osteocytes and chondrocytes in vitro. In order to examine the potential applications of hbASCs in breast reconstruction, an approach to promote in vitro differentiation of hbASCs into mammary gland‑like epithelial cells (MGECs) was developed using activated autologous platelet‑rich plasma (PRP). A proliferation phase and a subsequent morphological conversion phase were observed during this differentiation process. PRP significantly promoted the growth of hbASCs in the proliferation phase and increased the eventual conversion rate of hbASCs into MGECs. Thus, to the best of our knowledge, the present study provided the first comprehensive characterization of hbASCs and validated their multipotency. Furthermore, it was revealed that activated autologous PRP was able to enhance the differentiation efficiency of hbASCs into MGECs. The present study and other studies of hbASCs may aid the development of improved breast reconstruction strategies.

  1. [Progenotoxic shift in mammary adipose tissue (adipogenotoxicosis): association with clinical and biological characteristics of breast cancer].

    Science.gov (United States)

    Bershtein, L M; Kovalevskiĭ, A Iu; Poroshina, T E; Revskoĭ, S Iu; Kotov, A V; Kovalenko, I G; Tsyrlina, E V; Semiglazov, V F; Turkevich, E A; Pozharisskiĭ, K M

    2008-01-01

    The study is concerned with identification of a relationship between levels of production and accumulation of compounds capable of hormonal and progenotoxic effects in mammary fat, on the one hand, and characteristics of tumor tissue in breast cancer, on the other. Mammary fat was sampled at a distance of 1.5-2 cm from tumor edge (79 pts.). Case histories were used to provide data on clinical stage, size, grade and regional lymph node involvement. Levels were assayed of leptin, adiponectin, tumor necrosis factor (TNF-alpha), interleukin-6 (IL-6), nitric oxide (NO), thiobarbiturate-reactive products (TBRP) and DNA oxidative damage marker (8-OH-dG) from 4hr-incubates of fat tissue culture. Mammary fat aromatase was assayed by radiometrical means while macrophage-assisted fat infiltration (CD68) and estrogen-4-hydroxylase (CYP1B1) expression were evaluated immunohistochemically. Radio-competitive and immunohistochemical methods were used to assay estrogen (ER) and progesterone (PR) receptor levels in tumor and tumor-related expression of cytokeratins 5/6 ("basal") and 7/8 ("luminal" epithelium), respectively. As far as hormonal properties of mammary fat were concerned, there were direct correlations between aromatase concentration, on the one hand, and tumor stage and size, on the other, and adiponectin secretion and CK7 expression in tumor. Besides, an inverse correlation was found between mammary fat-mediated release of leptin and adiponectin, on the one hand, and stage and regional lymph node involvement, on the other. The following main relationships were identified by comparison of the clinico-biological characteristics of tumor and markers of proinflammatory/progenotoxic properties of mammary adipose tissue: tendency toward direct correlation with IL-6 and 8-OH-dG in fat (tumor progress stage); direct correlation with TNF-alpha secretion rate (malignancy grade); lymph node involvement--tendency toward direct correlation with NO generation; CK5 expression in

  2. Label-free biomolecular characterization of human breast cancer tissue with stimulated Raman scattering (SRS) spectral imaging (Conference Presentation)

    Science.gov (United States)

    Lu, Fa-Ke F.; Calligaris, David; Suo, Yuanzhen; Santagata, Sandro; Golby, Alexandra J.; Xie, X. Sunney; Mallory, Melissa A.; Golshan, Mehra; Dillon, Deborah A.; Agar, Nathalie Y. R.

    2017-02-01

    Stimulated Raman scattering (SRS) microscopy has been used for rapid label-free imaging of various biomolecules and drugs in living cells and tissues (Science, doi:10.1126/science.aaa8870). Our recent work has demonstrated that lipid and protein mapping of cancer tissue renders pathology-like images, providing essential histopathological information with subcellular resolution of the entire specimen (Cancer Research, doi: 10.1158/0008-5472.CAN-16-027). We have also established the first SRS imaging Atlas of human brain tumors (Harvard Dataverse, doi: (doi:10.7910/DVN/EZW4EK). SRS imaging of tissue could provide invaluable information for cancer diagnosis and surgical guidance in two aspects: rapid surgical pathology and quantitative biomolecular characterization. In this work, we present the use of SRS microscopy for characterization of a few essential biomolecules in breast cancer. Human breast cancer tissue specimens at the tumor core, tumor margin and normal area (5 cm away from the tumor) from surgical cases will be imaged with SRS at multiple Raman shifts, including the peaks for lipid, protein, blood (absorption), collagen, microcalcification (calcium phosphates and calcium oxalate) and carotenoids. Most of these Raman shifts have relatively strong Raman cross sections, which ensures high-quality and fast imaging. This proof-of-principle study is sought to demonstrate the feasibility and potential of SRS imaging for ambient diagnosis and surgical guidance of breast cancer.

  3. Tissue microarray analysis of eIF4E and its downstream effector proteins in human breast cancer

    Directory of Open Access Journals (Sweden)

    Clifford John

    2009-01-01

    Full Text Available Abstract Background Eukaryotic initiation factor 4E (eIF4E is elevated in many cancers and is a prognostic indicator in breast cancer. Many pro-tumorigenic proteins are selectively translated via eIF4E, including c-Myc, cyclin D1, ornithine decarboxylase (ODC, vascular endothelial growth factor (VEGF and Tousled-like kinase 1B (TLK1B. However, western blot analysis of these factors in human breast cancer has been limited by the availability of fresh frozen tissue and the labor-intensive nature of the multiple assays required. Our goal was to validate whether formalin-fixed, paraffin-embedded tissues arranged in a tissue microarray (TMA format would be more efficient than the use of fresh-frozen tissue and western blot to test multiple downstream gene products. Results Breast tumor TMAs were stained immunohistochemically and quantitated using the ARIOL imaging system. In the TMAs, eIF4E levels correlated strongly with c-Myc, cyclin D1, TLK1B, VEGF, and ODC. Western blot comparisons of eIF4E vs. TLK1B were consistent with the immunohistochemical results. Consistent with our previous western blot results, eIF4E did not correlate with node status, ER, PR, or HER-2/neu. Conclusion We conclude that the TMA technique yields similar results as the western blot technique and can be more efficient and thorough in the evaluation of several products downstream of eIF4E.

  4. Dissecting genetic requirements of human breast tumorigenesis in a tissue transgenic model of human breast cancer in mice.

    Science.gov (United States)

    Wu, Min; Jung, Lina; Cooper, Adrian B; Fleet, Christina; Chen, Lihao; Breault, Lyne; Clark, Kimberly; Cai, Zuhua; Vincent, Sylvie; Bottega, Steve; Shen, Qiong; Richardson, Andrea; Bosenburg, Marcus; Naber, Stephen P; DePinho, Ronald A; Kuperwasser, Charlotte; Robinson, Murray O

    2009-04-28

    Breast cancer development is a complex pathobiological process involving sequential genetic alterations in normal epithelial cells that results in uncontrolled growth in a permissive microenvironment. Accordingly, physiologically relevant models of human breast cancer that recapitulate these events are needed to study cancer biology and evaluate therapeutic agents. Here, we report the generation and utilization of the human breast cancer in mouse (HIM) model, which is composed of genetically engineered primary human breast epithelial organoids and activated human breast stromal cells. By using this approach, we have defined key genetic events required to drive the development of human preneoplastic lesions as well as invasive adenocarcinomas that are histologically similar to those in patients. Tumor development in the HIM model proceeds through defined histological stages of hyperplasia, DCIS to invasive carcinoma. Moreover, HIM tumors display characteristic responses to targeted therapies, such as HER2 inhibitors, further validating the utility of these models in preclinical compound testing. The HIM model is an experimentally tractable human in vivo system that holds great potential for advancing our basic understanding of cancer biology and for the discovery and testing of targeted therapies.

  5. Low or undetectable TPO receptor expression in malignant tissue and cell lines derived from breast, lung, and ovarian tumors

    Directory of Open Access Journals (Sweden)

    Erickson-Miller Connie L

    2012-09-01

    Full Text Available Abstract Background Numerous efficacious chemotherapy regimens may cause thrombocytopenia. Thrombopoietin receptor (TPO-R agonists, such as eltrombopag, represent a novel approach for the treatment of chemotherapy-induced thrombocytopenia. The TPO-R MPL is expressed on megakaryocytes and megakaryocyte precursors, although little is known about its expression on other tissues. Methods Breast, lung, and ovarian tumor samples were analyzed for MPL expression by microarray and/or quantitative reverse transcription-polymerase chain reaction (qRT-PCR, and for TPO-R protein expression by immunohistochemistry (IHC. Cell line proliferation assays were used to analyze the in vitro effect of eltrombopag on breast, lung, and ovarian tumor cell proliferation. The lung carcinoma cell lines were also analyzed for TPO-R protein expression by Western blot. Results MPL mRNA was not detectable in 118 breast tumors and was detectable at only very low levels in 48% of 29 lung tumors studied by microarray analysis. By qRT-PCR, low but detectable levels of MPL mRNA were detectable in some normal (14-43% and malignant (3-17% breast, lung, and ovarian tissues. A comparison of MPL to EPOR, ERBB2, and IGF1R mRNA demonstrates that MPL mRNA levels were far lower than those of EPOR and ERBB2 mRNA in the same tissues. IHC analysis showed negligible TPO-R protein expression in tumor tissues, confirming mRNA analysis. Culture of breast, lung, and ovarian carcinoma cell lines showed no increase, and in fact, showed a decrease in proliferation following incubation with eltrombopag. Western blot analyses revealed no detectable TPO-R protein expression in the lung carcinoma cell lines. Conclusions Multiple analyses of breast, lung, and ovarian tumor samples and/or cell lines show no evidence of MPL mRNA or TPO-R protein expression. Eltrombopag does not stimulate growth of breast, lung, or ovarian tumor cell lines at doses likely to exert their actions on megakaryocytes and

  6. CGH, cDNA and Tissue Microarray Analyses Implicate FGFR2 Amplification in a Small Subset of Breast Tumors

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    Mervi Heiskanen

    2001-01-01

    Full Text Available Multiple regions of the genome are often amplified during breast cancer development and progression, as evidenced in a number of published studies by comparative genomic hybridization (CGH. However, only relatively few target genes for such amplifications have been identified. Here, we indicate how small‐scale commercially available cDNA and CGH microarray formats combined with the tissue microarray technology enable rapid identification of putative amplification target genes as well as analysis of their clinical significance. According to CGH, the SUM‐52 breast cancer cell line harbors several high‐level DNA amplification sites, including the 10q26 chromosomal region where the fibroblast growth factor receptor 2 (FGFR2 gene has been localized. High level amplification of FGFR2 in SUM‐52 was identified using CGH analysis on a microarray of BAC clones. A cDNA microarray survey of 588 genes showed >40‐fold overexpression of FGFR2. Finally, a tissue microarray based FISH analysis of 750 uncultured primary breast cancers demonstrated in vivo amplification of the FGFR2 gene in about 1% of the tumors. In conclusion, three consecutive microarray (CGH, cDNA and tissue experiments revealed high‐level amplification and overexpression of the FGFR2 in a breast cancer cell line, but only a low frequency of involvement in primary breast tumors. Applied to a genomic scale with larger arrays, this strategy should facilitate identification of the most important target genes for cytogenetic rearrangements, such as DNA amplification sites detected by conventional CGH. Figures on http://www.esacp.org/acp/2001/22‐4/heiskanen.htm

  7. Dosimetric Evaluation of Three Partial Breast Irradiation Devices and the Dosimetric Effect of Tissue Thickness Surrounding a Multi-Lumen Partial Breast Applicator

    Science.gov (United States)

    Detwiler, Jordyn Ashle

    Many High Dose Rate treatment planning systems that are in use fail to correct for heterogeneities. If the treatment planning system does not correct for heterogeneities, it would assume that the patient is receiving full scatter when in reality, the patient will possibly be underdosed. A 1cm diameter planning target volume for a lumpectomy cavity could extend beyond the skin or chest wall for the patient and could be a great problem when it comes to treatment with the MammoSiteRTM single lumen breast applicator. A previous Monte Carlo study tested 3 MammoSiteRTM balloon sizes at various depths beyond the planning target volume to see how much tissue would be needed to achieve full scatter. The results showed that on average, if there was no tissue beyond the prescription line of 1cm there would be a 10% dose reduction for the breast -- skin interface. The purpose of this study is to use the Strut Adjusted Volume Implant (SAVI) multi-lumen breast applicator to re-create the measurements done with the MammoSiteRTM balloon and expand these measurements to include tissue thicknesses less than the PTV. Previous simulations with the MammoSiteRTM were done using Monte Carlo, with tissue thicknesses beyond the planning target volume of 0 -- 10cm. This study will re-create these measurements using Metal Oxide Semiconductor Field Effect Transistors (MOSFETs) and also take measurements below the prescription line of 1cm due to the ability of the SAVI applicator to adjust dose to the skin.

  8. Bothrops jararaca venom metalloproteinases are essential for coagulopathy and increase plasma tissue factor levels during envenomation.

    Directory of Open Access Journals (Sweden)

    Karine M Yamashita

    2014-05-01

    Full Text Available BACKGROUND/AIMS: Bleeding tendency, coagulopathy and platelet disorders are recurrent manifestations in snakebites occurring worldwide. We reasoned that by damaging tissues and/or activating cells at the site of the bite and systemically, snake venom toxins might release or decrypt tissue factor (TF, resulting in activation of blood coagulation and aggravation of the bleeding tendency. Thus, we addressed (a whether TF and protein disulfide isomerase (PDI, an oxireductase involved in TF encryption/decryption, were altered in experimental snake envenomation; (b the involvement and significance of snake venom metalloproteinases (SVMP and serine proteinases (SVSP to hemostatic disturbances. METHODS/PRINCIPAL FINDINGS: Crude Bothrops jararaca venom (BjV was preincubated with Na2-EDTA or AEBSF, which are inhibitors of SVMP and SVSP, respectively, and injected subcutaneously or intravenously into rats to analyze the contribution of local lesion to the development of hemostatic disturbances. Samples of blood, lung and skin were collected and analyzed at 3 and 6 h. Platelet counts were markedly diminished in rats, and neither Na2-EDTA nor AEBSF could effectively abrogate this fall. However, Na2-EDTA markedly reduced plasma fibrinogen consumption and hemorrhage at the site of BjV inoculation. Na2-EDTA also abolished the marked elevation in TF levels in plasma at 3 and 6 h, by both administration routes. Moreover, increased TF activity was also noticed in lung and skin tissue samples at 6 h. However, factor VII levels did not decrease over time. PDI expression in skin was normal at 3 h, and downregulated at 6 h in all groups treated with BjV. CONCLUSIONS: SVMP induce coagulopathy, hemorrhage and increased TF levels in plasma, but neither SVMP nor SVSP are directly involved in thrombocytopenia. High levels of TF in plasma and TF decryption occur during snake envenomation, like true disseminated intravascular coagulation syndrome, and might be implicated in

  9. Bothrops jararaca venom metalloproteinases are essential for coagulopathy and increase plasma tissue factor levels during envenomation.

    Science.gov (United States)

    Yamashita, Karine M; Alves, André F; Barbaro, Katia C; Santoro, Marcelo L

    2014-05-01

    Bleeding tendency, coagulopathy and platelet disorders are recurrent manifestations in snakebites occurring worldwide. We reasoned that by damaging tissues and/or activating cells at the site of the bite and systemically, snake venom toxins might release or decrypt tissue factor (TF), resulting in activation of blood coagulation and aggravation of the bleeding tendency. Thus, we addressed (a) whether TF and protein disulfide isomerase (PDI), an oxireductase involved in TF encryption/decryption, were altered in experimental snake envenomation; (b) the involvement and significance of snake venom metalloproteinases (SVMP) and serine proteinases (SVSP) to hemostatic disturbances. Crude Bothrops jararaca venom (BjV) was preincubated with Na2-EDTA or AEBSF, which are inhibitors of SVMP and SVSP, respectively, and injected subcutaneously or intravenously into rats to analyze the contribution of local lesion to the development of hemostatic disturbances. Samples of blood, lung and skin were collected and analyzed at 3 and 6 h. Platelet counts were markedly diminished in rats, and neither Na2-EDTA nor AEBSF could effectively abrogate this fall. However, Na2-EDTA markedly reduced plasma fibrinogen consumption and hemorrhage at the site of BjV inoculation. Na2-EDTA also abolished the marked elevation in TF levels in plasma at 3 and 6 h, by both administration routes. Moreover, increased TF activity was also noticed in lung and skin tissue samples at 6 h. However, factor VII levels did not decrease over time. PDI expression in skin was normal at 3 h, and downregulated at 6 h in all groups treated with BjV. SVMP induce coagulopathy, hemorrhage and increased TF levels in plasma, but neither SVMP nor SVSP are directly involved in thrombocytopenia. High levels of TF in plasma and TF decryption occur during snake envenomation, like true disseminated intravascular coagulation syndrome, and might be implicated in engendering bleeding manifestations in severely-envenomed patients.

  10. Bothrops jararaca venom metalloproteinases are essential for coagulopathy and increase plasma tissue factor levels during envenomation.

    Directory of Open Access Journals (Sweden)

    Karine M Yamashita

    2014-05-01

    Full Text Available BACKGROUND/AIMS: Bleeding tendency, coagulopathy and platelet disorders are recurrent manifestations in snakebites occurring worldwide. We reasoned that by damaging tissues and/or activating cells at the site of the bite and systemically, snake venom toxins might release or decrypt tissue factor (TF, resulting in activation of blood coagulation and aggravation of the bleeding tendency. Thus, we addressed (a whether TF and protein disulfide isomerase (PDI, an oxireductase involved in TF encryption/decryption, were altered in experimental snake envenomation; (b the involvement and significance of snake venom metalloproteinases (SVMP and serine proteinases (SVSP to hemostatic disturbances. METHODS/PRINCIPAL FINDINGS: Crude Bothrops jararaca venom (BjV was preincubated with Na2-EDTA or AEBSF, which are inhibitors of SVMP and SVSP, respectively, and injected subcutaneously or intravenously into rats to analyze the contribution of local lesion to the development of hemostatic disturbances. Samples of blood, lung and skin were collected and analyzed at 3 and 6 h. Platelet counts were markedly diminished in rats, and neither Na2-EDTA nor AEBSF could effectively abrogate this fall. However, Na2-EDTA markedly reduced plasma fibrinogen consumption and hemorrhage at the site of BjV inoculation. Na2-EDTA also abolished the marked elevation in TF levels in plasma at 3 and 6 h, by both administration routes. Moreover, increased TF activity was also noticed in lung and skin tissue samples at 6 h. However, factor VII levels did not decrease over time. PDI expression in skin was normal at 3 h, and downregulated at 6 h in all groups treated with BjV. CONCLUSIONS: SVMP induce coagulopathy, hemorrhage and increased TF levels in plasma, but neither SVMP nor SVSP are directly involved in thrombocytopenia. High levels of TF in plasma and TF decryption occur during snake envenomation, like true disseminated intravascular coagulation syndrome, and might be implicated in

  11. Correlation between the Expression of Aquaporin 1 and Hypoxia-inducible Factor 1 in Breast Cancer Tissues

    Institute of Scientific and Technical Information of China (English)

    Tiejun YIN; Shiying YU; Liang XIAO; Jun ZHANG; Chong LIU; Yunping LU; Chengping LIU

    2008-01-01

    The correlation between aquaporin 1 (AQP1) and hypoxia-inducible factor 1 (HIF 1) in breast cancer tissues was preliminarily studied. In 155 cases of breast cancer, the expression levels of AQP1 were detected by immunohistochemisty in HIF1-positive group or HIF1-negative group, and the correlation between AQP1 and HIF1 was analyzed. The overexpression of AQP1 and HIF1 were observed in 155 cases of breast cancer tissues. The expression level of AQP1 in HIF1-positive group was significantly higher than that in HIF1-negative group. The positive expression rate of AQP1 was 296.55±24.67 and 168.37±37.53 in HIF1-positive group and HIF1-negative group respectively with the difference being very significant between them (P<0.001). It was concluded that AQP1 was overexpressed in the HIF1-positive group and there were some correlations between AQP1 and HIF1, suggesting they interact each other and regulate the oncogenesis of breast cancer.

  12. Comparison of Nuclear Accumulation of p53 Protein with Mutations in the p53 Gene of Human Breast Cancer Tissues

    Institute of Scientific and Technical Information of China (English)

    王萱仪; 查小明; 武正炎; 范萍

    2001-01-01

    Objective The objective was to compare nuclear accumulation of p53 protein with mutations in the p53 gene on the tissues of human breast cancer. Methods Fifty-four invasive ductal carcinomas of breast were analyzed by the method of polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) silver stain and strep-avidin-biotin-peroxidase complex (SABC) immunohistochemistry. Results A statistically significant association between the presence of p53 gene mutation and nuclear accumulation of p53 protein was found (P<0.01). 22 tumors that demonstrated p53 gene mutations showed nuclear accumulation of p53 protein, while only 9 (28%) showed nuclear accumulation of p53 protein in 32 tumors without p53 gene mutations. Both p53 mutation protein and p53 gene mutations were prevalent in steroid and progesterone receptors negative tumors (P<0.05). A statistically significant association was found between the nuclear accumulation of p53 protein and lymph node invasion (P<0.05), and between p53 gene mutations and lymph node invasion (P<0.05). p53 abnormalities might be associated with an aggressive phenotype in breast cancer. Conclusion The immunohistochemical detection of nuclear p53 protein accumulation is highly associated with p53 gene mutations in breast cancer tissues, and that this method is useful for rapid screening of p53 abnormalities. However, in order to avoid false positive reaction, the p53 gene mutations should be determined in cases slightly positive for p53 nuclear protein.

  13. Label-Free Proteome Analysis of Plasma from Patients with Breast Cancer: Stage-Specific Protein Expression

    Science.gov (United States)

    Lobo, Marina Duarte Pinto; Moreno, Frederico Bruno Mendes Batista; Souza, Gustavo Henrique Martins Ferreira; Verde, Sara Maria Moreira Lima; Moreira, Renato de Azevedo; Monteiro-Moreira, Ana Cristina de Oliveira

    2017-01-01

    Breast cancer is one of the most commonly diagnosed types of cancer among women. Breast cancer mortality rates remain high probably because its diagnosis is hampered by inaccurate detection methods. Since changes in protein expression as well as modifications in protein glycosylation have been frequently reported in cancer development, the aim of this work was to study the differential expression as well as modifications of glycosylation of proteins from plasma of women with breast cancer at different stages of disease (n = 30) compared to healthy women (n = 10). A proteomics approach was used that depleted albumin and IgG from plasma followed by glycoprotein enrichment using immobilized Moraceae lectin (frutalin)-affinity chromatography and data-independent label-free mass spectrometric analysis. Data are available via ProteomeXchange with identifier PXD003106. As result, 57,016 peptides and 4,175 proteins among all samples were identified. From this, 40 proteins present in unbound (PI—proteins that did not interact with lectin) and bound (PII—proteins that interacted with lectin) fractions were differentially expressed. High levels of apolipoprotein A-II were detected here that were elevated significantly in the early and advanced stages of the disease. Apolipoprotein C-III was detected in both fractions, and its level was increased slightly in the PI fraction of patients with early-stage breast cancer and expressed at higher levels in the PII fraction of patients with early and intermediate stages. Clusterin was present at higher levels in both fractions of patients with early and intermediate stages of breast cancer. Our findings reveal a correlation between alterations in protein glycosylation, lipid metabolism, and the progression of breast cancer. PMID:28210565

  14. Study of electron densities of normal and neoplastic human breast tissues by Compton scattering using synchrotron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Antoniassi, M.; Conceicao, A.L.C. [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto-Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo (Brazil); Poletti, M.E., E-mail: poletti@ffclrp.usp.br [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto-Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo (Brazil)

    2012-07-15

    Electron densities of 33 samples of normal (adipose and fibroglangular) and neoplastic (benign and malignant) human breast tissues were determined through Compton scattering data using a monochromatic synchrotron radiation source and an energy dispersive detector. The area of Compton peaks was used to determine the electron densities of the samples. Adipose tissue exhibits the lowest values of electron density whereas malignant tissue the highest. The relationship with their histology was discussed. Comparison with previous results showed differences smaller than 4%. - Highlights: Black-Right-Pointing-Pointer Electron density of normal and neoplastic breast tissues was measured using Compton scattering. Black-Right-Pointing-Pointer Monochromatic synchrotron radiation was used to obtain the Compton scattering data. Black-Right-Pointing-Pointer The area of Compton peaks was used to determine the electron densities of samples. Black-Right-Pointing-Pointer Adipose tissue shows the lowest electron density values whereas the malignant tissue the highest. Black-Right-Pointing-Pointer Comparison with previous results showed differences smaller than 4%.

  15. A nationwide study of connective tissue disease and other rheumatic conditions among Danish women with long-term cosmetic breast implantation

    DEFF Research Database (Denmark)

    Fryzek, Jon P; Holmich, Lisbet; McLaughlin, Joseph K

    2007-01-01

    PURPOSE: Numerous epidemiologic studies have demonstrated that breast implants are not associated with connective tissue diseases (CTDs). However, many CTDs are rare, and continued follow-up of women with breast implants is warranted. METHODS: We extended by 5 years the follow-up of our earlier...

  16. Quantitative Assessment of Breast Parenchymal Uptake on 18F-FDG PET/CT: Correlation with Age, Background Parenchymal Enhancement, and Amount of Fibroglandular Tissue on MRI.

    Science.gov (United States)

    Leithner, Doris; Baltzer, Pascal A; Magometschnigg, Heinrich F; Wengert, Georg J; Karanikas, Georgios; Helbich, Thomas H; Weber, Michael; Wadsak, Wolfgang; Pinker, Katja

    2016-10-01

    Background parenchymal enhancement (BPE), and the amount of fibroglandular tissue (FGT) assessed with MRI have been implicated as sensitive imaging biomarkers for breast cancer. The purpose of this study was to quantitatively assess breast parenchymal uptake (BPU) on (18)F-FDG PET/CT as another valuable imaging biomarker and examine its correlation with BPE, FGT, and age.

  17. Adipose-derived stem cells and platelet-rich plasma: the keys to functional periodontal tissue engineering.

    Science.gov (United States)

    Tobita, Morikuni; Mizuno, Hiroshi

    2013-09-01

    Numerous different types of periodontal tissue regeneration therapies have been developed clinically with variable outcomes and serious limitations. A key goal of periodontal therapy is to regenerate the destroyed periodontal tissues including alveolar bone, cementum and periodontal ligament. The critical factors in attaining successful periodontal tissue regeneration are the correct recruitment of cells to the site and the production of a suitable extra cellular matrix consistent with the periodontal tissues. Adipose tissue, from which mesenchymal stem cells can be harvested easily and safely, is an especially attractive stem cell source, because adipose-derived stem cells have a strong potential for cell differentiation and growth factor secretion. Meanwhile, the usefulness of platelet-rich plasma in the field of dental surgery has attracted attention. Therapeutic effects of platelet-rich plasma are believed to occur through the provision of concentrated levels of platelet-derived growth factors. Further, recent reports suggested the effect of platelet-rich plasma on mesenchymal stem cell proliferation, differentiation and survival rate. Therefore, the admixture of mesenchymal stem cells and platelet-rich plasma may indicate the great potential for tissue regenerations including periodontal tissue regeneration. In this review, the potential of adipose-derived stem cells and platelet-rich plasma is introduced. Of particular interest, the usefulness in periodontal tissue regeneration and future perspective is discussed.

  18. Prognostic value of pre-surgical plasma PAI-1 (plasminogen activator inhibitor-1) levels in breast cancer.

    Science.gov (United States)

    Palmirotta, Raffaele; Ferroni, Patrizia; Savonarola, Annalisa; Martini, Francesca; Ciatti, Filippo; Laudisi, Anastasia; Sini, Valentina; Del Monte, Girolamo; Guadagni, Fiorella; Roselli, Mario

    2009-09-01

    Plasminogen activator inhibitor (PAI-1) may have an independent prognostic value in breast cancer (BC). PAI-1 4G/5G polymorphism may have significance for antigen expression. Thus, we analyzed the possible associations between PAI-1 4G/5G polymorphism, plasma PAI-1 levels, and clinicopathological features of breast cancer (BC) patients. PAI-1 4G/5G polymorphism (both on germinal and tumor DNA) and plasma PAI-1 levels were investigated in 99 BC patients and 50 unrelated healthy women similar for age and menopausal status. No association was found between allele frequencies and clinicopathological features of BC or plasma antigen levels. Plasma PAI-1 levels were higher in BC compared to controls (p=0.002), particularly in patients with large tumors (p<0.001). 5-year follow-up was achieved in 79 patients: 30% had relapsing disease, 63% with positive compared to 37% with negative PAI-1 levels (p<0.05). 5-year relapse-free survival rate of positive PAI-1 was 46% vs., 77% of negative patients (p=0.02). We may conclude that plasma PAI-1 levels in BC patients could represent a useful prognostic variable for relapse, although PAI-1 polymorphism might not represent a genetic susceptibility factor.

  19. Bilateral Gigantomastia, Multiple Synchronous Nodular Pseudoangiomatous Stromal Hyperplasia Involving Breast and Bilateral Axillary Accessory Breast Tissue, and Perianal Mammary-Type Hamartoma of Anogenital Mammary-Like Glands: A Case Report.

    Science.gov (United States)

    Hayes, Malcolm M; Konstantinova, Anastasia M; Kacerovska, Denisa; Michal, Michal; Kreuzberg, Boris; Suvova, Bozena; Kazakov, Dmitry V

    2016-05-01

    Mammary-type fibroepithelial lesions involving ectopic breast and anogenital region are rare and usually coexist with normal orthotopic breast. We present what we believe to be a unique case of synchronous bilateral gestational gigantomastia resembling fibrous mastopathy, synchronous rapidly growing pregnancy-associated nodular pseudoangiomatous stromal hyperplasia involving right breast and bilateral axillary ectopic breast tissue, and metachronous perianal mammary-type hamartoma involving anogenital mammary-like glands occurring in a 34-year-old patient with facioscapulohumeral muscular dystrophy. Also, we review the literature concerning these lesions.

  20. Quantifying collagen orientation in breast tissue biopsies using SLIM (Conference Presentation)

    Science.gov (United States)

    Majeed, Hassaan; Okoro, Chukwuemeka; Balla, Andre; Toussaint, Kimani C.; Popescu, Gabriel

    2017-02-01

    Breast cancer is a major public health problem worldwide, being the most common type of cancer among women according to the World Health Organization (WHO). The WHO has further stressed the importance of an early determination of the disease course through prognostic markers. Recent studies have shown that the alignment of collagen fibers in tumor adjacent stroma correlate with poorer health outcomes in patients. Such studies have typically been carried out using Second-Harmonic Generation (SHG) microscopy. SHG images are very useful for quantifying collagen fiber orientation due their specificity to non-centrosymmetric structures in tissue, leading to high contrast in collagen rich areas. However, the imaging throughput in SHG microscopy is limited by its point scanning geometry. In this work, we show that SLIM, a wide-field high-throughput QPI technique, can be used to obtain the same information on collagen fiber orientation as is obtainable through SHG microscopy. We imaged a tissue microarray containing both benign and malignant cores using both SHG microscopy and SLIM. The cellular (non-collagenous) structures in the SLIM images were next segmented out using an algorithm developed in-house. Using the previously published Fourier Transform Second Harmonic Generation (FT-SHG) tool, the fiber orientations in SHG and segmented SLIM images were then quantified. The resulting histograms of fiber orientation angles showed that both SHG and SLIM generate similar measurements of collagen fiber orientation. The SLIM modality, however, can generate these results at much higher throughput due to its wide-field, whole-slide scanning capabilities.

  1. Plasma extravasation mediated by lipopolysaccharide-induction of kinin B1 receptors in rat tissues

    Directory of Open Access Journals (Sweden)

    Paulo Roberto Wille

    2001-01-01

    Full Text Available The present study was performed to: (a evaluate the effects of kinin B1 (Sar{D-Phe8}-des-Arg9-BK; 10 nmol/kg and B2 (bradykinin (BK; 10 nmol/kg receptor agonists on plasma extravasation in selected rat tissues; (b determine the contribution of a lipopolysaccharide (LPS (100 μ g/kg to the effects triggered by B1 and B2 agonists; and (c characterize the selectivity of B1 ({Leu8}desArg9-BK; 10 nmol/kg and B2 (HOE 140; 10 nmol/kg antagonists as inhibitors of this kinin-induced phenomenon. B1 and B2 agonists were shown to increase plasma extravasation in the duodenum, ileum and also in the urinary bladder of the rat. LPS pretreatment enhanced the plasma extravasation mediated only by the B1 agonist in the duodenum, ileum, trachea, main and segmentar bronchi. These effects were prevented by the B1. but not the B2 antagonist. In normal rats, the B2 antagonist inhibited the effect of B2 agonist in all the tissues analyzed. However, in LPS-treated rats, the B2 antagonist was ineffective in the urinary bladder.

  2. Plasma, tissue and urinary levels of aloin in rats after the administration of pure aloin.

    Science.gov (United States)

    Park, Mi-Young; Kwon, Hoon-Jeong; Sung, Mi-Kyung

    2008-01-01

    Aloin is a physiologically active anthraquinone present in aloe. There are two isomers of aloin, aloin A and aloin B, occurring as a mixture of diastereomers. The objective of this study was to determine the bioavailability and tissue distribution of aloin. Rats were gavaged with 11.8g/kg aloin, and the levels of aloin and its conjugates were measured in plasma, tissues, and urine. Plasma aloin level showed a peak at 1hr after the administration and the concentration was 59.07+/-10.5 ng/ml. The 24 h cumulated urinary aloin was 0.03% of the initial dose. These results suggest that aloin is absorbed and reaches a peak plasma level within 1-1.5 h after the administration and a significant portion is possibly metabolized or is excreted in feces. These results can apply to the determination of the adequate intake level of aloe and aloe products to achieve the desired biological effect, and to interprete in vitro study results.

  3. Searching for anthropogenic contaminants in human breast adipose tissues using gas chromatography-time-of-flight mass spectrometry

    OpenAIRE

    Hernández Hernández, Félix; Portolés Nicolau, Tania; Pitarch Arquimbau, María Elena; López Benet, Francisco José

    2008-01-01

    The potential of GC-TOF MS for screening anthropogenic organic contaminants in human breast adipose tissues has been investigated. Initially a target screening was performed for a list of 125 compounds which included persistent halogen pollutants (OC pesticides, PCBs, PBDEs), PAHs, alkylphenols, and a notable number of pesticides from the different fungicide, herbicide and insecticide families. Searching for target pollutants was done by evaluating the presence of up to five representative io...

  4. Identification of immune cell infiltration in hematoxylin-eosin stained breast cancer samples: texture-based classification of tissue morphologies

    Science.gov (United States)

    Turkki, Riku; Linder, Nina; Kovanen, Panu E.; Pellinen, Teijo; Lundin, Johan

    2016-03-01

    The characteristics of immune cells in the tumor microenvironment of breast cancer capture clinically important information. Despite the heterogeneity of tumor-infiltrating immune cells, it has been shown that the degree of infiltration assessed by visual evaluation of hematoxylin-eosin (H and E) stained samples has prognostic and possibly predictive value. However, quantification of the infiltration in H and E-stained tissue samples is currently dependent on visual scoring by an expert. Computer vision enables automated characterization of the components of the tumor microenvironment, and texture-based methods have successfully been used to discriminate between different tissue morphologies and cell phenotypes. In this study, we evaluate whether local binary pattern texture features with superpixel segmentation and classification with support vector machine can be utilized to identify immune cell infiltration in H and E-stained breast cancer samples. Guided with the pan-leukocyte CD45 marker, we annotated training and test sets from 20 primary breast cancer samples. In the training set of arbitrary sized image regions (n=1,116) a 3-fold cross-validation resulted in 98% accuracy and an area under the receiver-operating characteristic curve (AUC) of 0.98 to discriminate between immune cell -rich and - poor areas. In the test set (n=204), we achieved an accuracy of 96% and AUC of 0.99 to label cropped tissue regions correctly into immune cell -rich and -poor categories. The obtained results demonstrate strong discrimination between immune cell -rich and -poor tissue morphologies. The proposed method can provide a quantitative measurement of the degree of immune cell infiltration and applied to digitally scanned H and E-stained breast cancer samples for diagnostic purposes.

  5. Skin and Subcutaneous Tissue Ultrasonography Features in Breast Cancer-Related Lymphedema

    Science.gov (United States)

    Morikage, Noriyasu; Yamashita, Osamu; Harada, Takasuke; Samura, Makoto; Takeuchi, Yuriko; Mizoguchi, Takahiro; Nakamura, Kaori; Hamano, Kimikazu

    2016-01-01

    Objective: To investigate skin, subepidermal low echogenic band (SELEB), and subcutaneous tissue (SCT) thickness as well as the degree of increase in subcutaneous echogenicity (SEG) and subcutaneous echo-free space (SEFS) in arms with lymphedema (LE). Materials and Methods: The skin and SCT of both arms of 30 patients with unilateral stage II breast cancer-related LE were scanned at five points (medial/lateral upper arm/forearm and dorsum of the hand). SEG and SEFS grades were determined according to severity (range: 0–2). Results: All measured parameters, except the SEFS in the medial upper arm, were significantly higher on the LE side than on the normal (N) side. The parameters differed most remarkably in the medial forearm (MFA; skin: LE 1.7 ± 0.8 mm vs. N 0.8 ± 0.2 mm; SELEB: LE 1.0 ± 0.6 mm vs. N 0.3 ± 0.1 mm; SCT: LE 8.7 ± 3.4 mm vs. N 3.8 ± 2.0 mm; SEG: LE 0.9 ± 0.5 vs. N 0.1 ± 0.3; and SEFS: LE 0.5 ± 0.7 vs. N 0). Conclusion: The differences in the thickness of the skin, SELEB, and SCT and the SEG and SEFS grades between the LE and N arms seemed most evident in the MFA. PMID:28018504

  6. Detection of soft tissue densities from digital breast tomosynthesis: comparison of conventional and deep learning approaches

    Science.gov (United States)

    Fotin, Sergei V.; Yin, Yin; Haldankar, Hrishikesh; Hoffmeister, Jeffrey W.; Periaswamy, Senthil

    2016-03-01

    Computer-aided detection (CAD) has been used in screening mammography for many years and is likely to be utilized for digital breast tomosynthesis (DBT). Higher detection performance is desirable as it may have an impact on radiologist's decisions and clinical outcomes. Recently the algorithms based on deep convolutional architectures have been shown to achieve state of the art performance in object classification and detection. Similarly, we trained a deep convolutional neural network directly on patches sampled from two-dimensional mammography and reconstructed DBT volumes and compared its performance to a conventional CAD algorithm that is based on computation and classification of hand-engineered features. The detection performance was evaluated on the independent test set of 344 DBT reconstructions (GE SenoClaire 3D, iterative reconstruction algorithm) containing 328 suspicious and 115 malignant soft tissue densities including masses and architectural distortions. Detection sensitivity was measured on a region of interest (ROI) basis at the rate of five detection marks per volume. Moving from conventional to deep learning approach resulted in increase of ROI sensitivity from 0:832 +/- 0:040 to 0:893 +/- 0:033 for suspicious ROIs; and from 0:852 +/- 0:065 to 0:930 +/- 0:046 for malignant ROIs. These results indicate the high utility of deep feature learning in the analysis of DBT data and high potential of the method for broader medical image analysis tasks.

  7. Biobanking sustainability--experiences of the Australian Breast Cancer Tissue Bank (ABCTB).

    Science.gov (United States)

    Carpenter, Jane E; Clarke, Christine L

    2014-12-01

    Sustainability of biorepositories is a key issue globally. This article is a description of the different strategies and mechanisms used by the Australian Breast Cancer Tissue Bank (ABCTB) in developing and operating the resource since its inception in 2005. ABCTB operates according to a hub and spoke model, with a central management hub that is responsible for overall management of the resource including financial, ethical, and legal processes, researcher applications for material, clinical follow-up, information/database activities, and security. A centralized processing laboratory also operates from the hub site where DNA and RNA extractions are performed, digital imaging of stained tumor sections occurs, and specimens are assembled for dispatch for research projects. ABCTB collection sites where donors are identified, consent obtained, and specimens collected and processed for initial storage are located across Australia. Each of the activities of the resource requires financial support and different sources of revenue, some of which are allocated to a specific function of the ABCTB. Different models are in use at different collection centers where local variations may exist and local financial support may sometimes be obtained. There is also significant in-kind support by clinics and diagnostic and research facilities that house the various activities of the resource. However, long-term financial commitment to ensure the survival of the resource is not in place, and forward planning of operations remains challenging under these circumstances.

  8. [Axillary ectopic breast tissue fibroadenoma: report of three cases and review of the literature].

    Science.gov (United States)

    Ortiz-Mendoza, Carlos Manuel

    2012-02-01

    Ninety-five percent of women have mammary tissue at the axilla. However, the fibroadenoma seldom occur in this area and there are only isolated case reports of this tumor. This paper presents a series of three cases of this rare entity. Three women came to our hospital by axillary lumps. The patients had a median age of 36 +/- 9-years-old with an average time of evolution of 34 +/- 53 months. One patient had the history of a breast phyllodes tumor previously excised, and two were nulliparous. In two cases, neither ultrasound nor mammogram gave useful information for its diagnosis. Mammary glands of all cases were normal. The tumors were firm and movable, similar to a lymphadenopathy, and one was evident. The mean tumor size was 28 +/- 18 mm; all were oval and with white appearance. Histological diagnosis for all cases was fibroadenoma. Our findings match with literature reports. The axillary fibroadenomas may occur in women aged 30 to 50-years-old, mimicking a lymphadenopathy. Finally, the ultrasound and the mammography are not useful tools for its diagnosis.

  9. Study of the Effect of Breast Tissue Density on Detection of Masses in Mammograms

    Directory of Open Access Journals (Sweden)

    A. García-Manso

    2013-01-01

    Full Text Available One of the parameters that are usually stored for mammograms is the BI-RADS density, which gives an idea of the breast tissue composition. In this work, we study the effect of BI-RADS density in our ongoing project for developing an image-based CAD system to detect masses in mammograms. This system consists of two stages. First, a blind feature extraction is performed for regions of interest (ROIs, using Independent Component Analysis (ICA. Next, in the second stage, those features form the input vectors to a classifier, neural network, or SVM classifier. To train and test our system, the Digital Database for Screening Mammography (DDSM was used. The results obtained show that the maximum variation in the performance of our system considering only prototypes obtained from mammograms with a concrete value of density (both for training and test is about 7%, yielding the best values for density equal to 1, and the worst for density equal to 4, for both classifiers. Finally, with the overall results (i.e., using prototypes from mammograms with all the possible values of densities, we obtained a difference in performance that is only 2% lower than the maximum, also for both classifiers.

  10. Management of a case of Mucor colonization in breast tissue expander seroma pocket

    Directory of Open Access Journals (Sweden)

    Danielle N. Atwood

    2017-06-01

    Full Text Available Mucormycosis is a rare and potentially life-threatening opportunistic infection with approximately 500 cases per year in the United States (Spellberg et al., 2005. There are six major presentations, which include rhino-orbital-cerebral, pulmonary, cutaneous, gastrointestinal, disseminated, and uncommon (e.g. osteomyelitis, endocarditis Petrikkos et al. (2012.2 While not a prominent pathogen in immunocompetent patients, immunocompromised patients such as those with prolonged neutropenia, organ and/or bone marrow suppression, and diabetes mellitus are prone to dissemination resulting in rapid death without prompt intervention (Spellberg et al. 2005. With a mortality rate reaching 90% (Spellberg et al. 2005, it is imperative that therapy be initiated rapidly once a diagnosis is made. Successful treatment consists of management of underlying risk factors, surgical debridement, and antifungal therapies (Spellberg et al. 2005. The dilemma whether to pursue extensive debridement presents when the wound is cultured positive but the patient is not systemically ill. We present the first reported case of successful salvage of breast reconstruction with retention of tissue extender and acellular dermal matrix (ADM despite colonization of a recalcitrant seroma pocket by Mucor.

  11. Impairment of liver synthetic function and the production of plasma proteins in primary breast cancer patients on doxorubicincyclophosphamide (AC) protocol.

    Science.gov (United States)

    Saleem, Zikria; Ahmad, Mobasher; Hashmi, Furqan Khurshid; Saeed, Hamid; Aziz, Muhammad Tahir

    2016-09-01

    Doxorubicin and Cyclophosphamide (AC protocol) combination is usually considered as a first line therapy in newly diagnosed breast cancer patients. Thus, a retrospective observational study was conducted to monitor the effect of AC protocol on liver synthetic functions and production of plasma proteins in breast cancer patients, reporting to specialized cancer care hospital of Lahore, Pakistan. A total of 75 patients (n=75) on AC protocol with breast cancer were observed in this study. The patient data including age, gender, body surface area, dosage, disease status and laboratory biochemical values were recorded by reviewing historical treatment records. Pre-treatment values were taken as baseline values for albumin, globulin, blood urea nitrogen (BUN), albumin/globulin (A/G) ratio and total proteins. The baseline values were compared after each cycle of by applying ANOVA using statistical tool SPSS® version 21. The plasma levels of blood urea nitrogen (BUN), total protein and globulin dropped significantly (p0.05). The A/G ratio level increased (pliver synthetic functions as observed by decreased blood urea nitrogen (BUN) and plasma protein levels.

  12. Tumor tissue levels of tissue inhibitor of metalloproteinases-I (TIMP-I) and outcome following adjuvant chemotherapy in premenopausal lymph node-positive breast cancer patients

    DEFF Research Database (Denmark)

    Schrohl, Anne-Sofie; Look, Maxime P.; Gelder, Marion E. Meijer-van

    2009-01-01

    an association between shorter survival after treatment in TIMP-1 high patients compared with TIMP-1 low patients, especially in patients receiving anthracycline-based therapy. This suggests that high tumor tissue levels of TIMP-1 might be associated with reduced benefit from classical adjuvant chemotherapy. Our......BACKGROUND: We have previously demonstrated that high tumor tissue levels of TIMP-1 are associated with no or limited clinical benefit from chemotherapy with CMF and anthracyclines in metastatic breast cancer patients. Here, we extend our investigations to the adjuvant setting studying outcome...... after adjuvant chemotherapy in premenopausal lymph node-positive patients. We hypothesize that TIMP-1 high tumors are less sensitive to chemotherapy and accordingly that high tumor tissue levels are associated with shorter survival. METHODS: From our original retrospectively collected tumor samples we...

  13. Nationwide survey of glandular tissue doses for the establishment of a breast cancer screening system using mammography. Analysis of technical parameters affecting the glandular tissue dose

    Energy Technology Data Exchange (ETDEWEB)

    Higashida, Yoshiharu [Kyushu Univ., Fukuoka (Japan). School of Health Sciences; Hagiwara, Akira; Asahara, Masaki [and others

    2000-09-01

    The effects of technical parameters, such as screen-film combinations, antiscatter grids, processing conditions and X-ray beam qualities, on the average glandular tissue dose of radiation were analyzed under two exposure conditions: The standard radiographic condition for an RMI 156 phantom at each facility (Standard Radiographic Condition). The radiographic condition needed to obtain a radiographic density of 1.20 to 1.40 with an RMI 156 phantom (Canonical Radiographic Condition). The analysis included 208 dose measurements at 104 facilities. The results showed that the average glandular tissue dose depends strongly on the grid types and screen-film combinations used. There were also significant differences in radiographic density between the Standard Radiographic Condition and the Canonical Radiographic Condition. This analysis of the technical parameters affecting the glandular tissue dose will be useful in establishing a standardized mammographic breast cancer screening system. (author)

  14. Phenotypic changes of p53, HER2, and FAS system in multiple normal tissues surrounding breast cancer.

    Science.gov (United States)

    Mottolese, Marcella; Nádasi, Edit A; Botti, Claudio; Cianciulli, Anna M; Merola, Roberta; Buglioni, Simonetta; Benevolo, Maria; Giannarelli, Diana; Marandino, Ferdinando; Donnorso, Raffaele Perrone; Venturo, Irene; Natali, Pier Giorgio

    2005-07-01

    To determine whether phenotypic field changes occur in tissues adjacent to carcinoma, we assayed, by immunohistochemistry, the expression of HER-2, p53, Fas, and FasL in 72 breast cancers (BC) and multiple autologous peritumoral tissues (PTTs) sampled up to 5 cm distance and in 44 benign breast tumors (BBTs). About 5% and 3% of the PTTs and 4.5% and 6.8% of BBTs showed alterations in HER2 and p53 expression, respectively. Of interest, gene amplification was observed in 50% of HER2 positive PTTs, but not in any HER2 positive BBTs. Fas, highly expressed in BBTs and downregulated in BC, maintained its expression in PTTs, whereas FasL, usually negative in BBTs, was upregulated in BC as well as in the PTTs closest (1 cm) to the invasive lesion. Our data suggest that FasL could be a potential novel biomarker of transformation, which may identify, along with HER2 and p53, precursor lesions in a genetically altered breast tissue.

  15. Non-invasive optical estimate of tissue composition to differentiate malignant from benign breast lesions: A pilot study

    Science.gov (United States)

    Taroni, Paola; Paganoni, Anna Maria; Ieva, Francesca; Pifferi, Antonio; Quarto, Giovanna; Abbate, Francesca; Cassano, Enrico; Cubeddu, Rinaldo

    2017-01-01

    Several techniques are being investigated as a complement to screening mammography, to reduce its false-positive rate, but results are still insufficient to draw conclusions. This initial study explores time domain diffuse optical imaging as an adjunct method to classify non-invasively malignant vs benign breast lesions. We estimated differences in tissue composition (oxy- and deoxyhemoglobin, lipid, water, collagen) and absorption properties between lesion and average healthy tissue in the same breast applying a perturbative approach to optical images collected at 7 red-near infrared wavelengths (635–1060 nm) from subjects bearing breast lesions. The Discrete AdaBoost procedure, a machine-learning algorithm, was then exploited to classify lesions based on optically derived information (either tissue composition or absorption) and risk factors obtained from patient’s anamnesis (age, body mass index, familiarity, parity, use of oral contraceptives, and use of Tamoxifen). Collagen content, in particular, turned out to be the most important parameter for discrimination. Based on the initial results of this study the proposed method deserves further investigation. PMID:28091596

  16. Non-invasive optical estimate of tissue composition to differentiate malignant from benign breast lesions: A pilot study

    Science.gov (United States)

    Taroni, Paola; Paganoni, Anna Maria; Ieva, Francesca; Pifferi, Antonio; Quarto, Giovanna; Abbate, Francesca; Cassano, Enrico; Cubeddu, Rinaldo

    2017-01-01

    Several techniques are being investigated as a complement to screening mammography, to reduce its false-positive rate, but results are still insufficient to draw conclusions. This initial study explores time domain diffuse optical imaging as an adjunct method to classify non-invasively malignant vs benign breast lesions. We estimated differences in tissue composition (oxy- and deoxyhemoglobin, lipid, water, collagen) and absorption properties between lesion and average healthy tissue in the same breast applying a perturbative approach to optical images collected at 7 red-near infrared wavelengths (635–1060 nm) from subjects bearing breast lesions. The Discrete AdaBoost procedure, a machine-learning algorithm, was then exploited to classify lesions based on optically derived information (either tissue composition or absorption) and risk factors obtained from patient’s anamnesis (age, body mass index, familiarity, parity, use of oral contraceptives, and use of Tamoxifen). Collagen content, in particular, turned out to be the most important parameter for discrimination. Based on the initial results of this study the proposed method deserves further investigation.

  17. The value of archival tissue blocks in understanding breast cancer biology.

    Science.gov (United States)

    Dowsett, Thomas; Verghese, Eldo; Pollock, Steven; Pollard, Jennifer; Heads, Judith; Hanby, Andrew; Speirs, Valerie

    2014-03-01

    Pathological reporting of breast cancer has evolved alongside scientific advances. Such advances have led to recognition of different molecular classes of breast cancer resulting in improved disease management. The aim of this study was to establish whether these advances could be applied to archival breast cancer cases dating from the 1940s to assess historical trends. Important observations included the marked differences in pathological reporting, size of tumour and in ERα expression throughout the decades.

  18. Healing of grafted adipose tissue: current clinical applications of adipose-derived stem cells for breast and face reconstruction.

    Science.gov (United States)

    Philips, Brian J; Marra, Kacey G; Rubin, J Peter

    2014-05-01

    Since their isolation and characterization nearly a decade ago, adipose-derived stem cells (ASCs) have become one of the most popular adult stem cell populations for soft tissue engineering and regenerative medicine applications. Compared with other stem cell sources, ASCs offer several advantages including abundant autologous source, minor invasive harvesting (liposuction), significant proliferative capacity in culture, and multilineage potential. In this mini review, we focus on some of the more salient published clinical and preclinical data to date regarding ASC treatment for breast and facial soft tissue reconstruction. © 2014 by the Wound Healing Society.

  19. Study of neuropeptide Y in the plasma and skin tissue of patients with vitiligo

    Institute of Scientific and Technical Information of China (English)

    ZENG Wei-hui; TANG Sheng-shun; ZHENG Yan; LEI Xiao-bing

    2004-01-01

    Objective: To study the role of neuropeptide Y (NPY) in the pathogenesis of vitiligo. Methods: The levels of NPY in the plasma from patients with vitiligo and healthy volunteers were measured by 125 I RIA Kit. The expression of NPY in normal skin tissues, uninvolved tissues and lesional tissues of vitiligo was detected by immunohistochemistry. Results: The levels of NPY in the patients with vitiligo of all types were significantly higher than that in the normal controls. In all types, the levels in active stage were significantly higher than those in stable stage. The expression of NPY was upregulated in lesions of patients with active vitiligo ( P < 0.01) compared with those in normal skin tissues and uninvolved tissues.There was significant difference of NPY expression between active stage and stable stage (P < 0.01 ). Conclusion: These findings support the concept of neuropeptide involvement in vitiligo, especially in active vitiligo, and suggest that NPY may play a role in the pathogenesis of this disease.

  20. Physiological comparisons of plasma and tissue metrics of selected inland and coastal steelhead kelts.

    Science.gov (United States)

    Penney, Zachary L.; Moffitt, Christine M.; Jones, Bryan; Marston, Brian

    2016-01-01

    The physiological status of migrating steelhead kelts (Oncorhynchus mykiss) from the Situk River, Alaska, and two tributaries of the Clearwater River, Idaho, was evaluated to explore potential differences in post-spawning survival related to energy reserves. Blood plasma samples were analyzed for metrics related to nutritional and osmotic status, and samples of white muscle tissue collected from recent mortalities at weirs were analyzed for proximate constituents. Female kelts from the Situk River had significantly higher plasma cholesterol, triglycerides, glucose and calcium concentrations, all of which suggested higher lipid and energy stores. Additional support for energy limitation in kelts was provided by evaluating the presence of detectable proteins in the plasma. Most all kelts sampled from the Situk River populations had detectable plasma proteins, in contrast to kelts sampled from the Clearwater River tributary populations where 27 % of kelts from one tributary, and 68 % of the second tributary were below the limits of detection. We found proximate constituents of kelt mortalities were similar between the Situk and Clearwater River populations, and the lipid fraction of white muscle averaged 0.1 and 0.2 %. Our findings lend support to the hypothesis that energetic limitations likely affect post-spawn survival in the Clearwater River kelts.

  1. ENO1 Protein Levels in the Tumor Tissues and Circulating Plasma Samples of Non-small Cell Lung Cancer Patients

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    Ying ZHANG

    2010-12-01

    Full Text Available Background and objective Proper tumor markers are useful to diagnosis, prognosis and treatment for lung cancer. The aim of this study is to examine the levels of alpha-enolase (ENO1 protein in the tumor tissues and peripheral plasma samples obtained from non-small cell lung cancer (NSCLC patients, and evaluate its potential clinical significance. Methods The ENO1 protein levels in the tumor tissues and corresponding normal tissues from 16 cases of lung squamous cell carcinoma were analyzed by Western blot. The ENO1 protein levels in the plasma samples from 42 healthy individuals, 34 patients with lung benign disease and 84 patients with NSCLC were measured by double antibody sandwich enzyme-linked immunosorbent assay. Results For 87.5% (14/16 of the patients with lung squamous cell carcinoma, the ENO1 protein level in the tumor tissues was higher than that in the corresponding normal lung tissues. The ENO1 protein level in the plasma of NSCLC patients was significantly higher than that in the plasma of healthy individuals (P=0.031 and patients with lung benign disease (P=0.019. Furthermore, the ENO1 protein level was significantly higher in the plasma of patients with lung adenocarcinoma than that of patients with lung squamous cell carcinoma. Conclusion The elevated levels of ENO1 protein in the tumor tissues and the plasma samples from NSCLC patients indicate ENO1 may be a candidate biomarker of lung cancer.

  2. Adipose tissue interleukin-18 mRNA and plasma interleukin-18: effect of obesity and exercise

    DEFF Research Database (Denmark)

    Leick, Lotte; Lindegaard, Birgitte; Stensvold, Dorthe

    2007-01-01

    OBJECTIVES: Obesity and a physically inactive lifestyle are associated with increased risk of developing insulin resistance. The hypothesis that obesity is associated with increased adipose tissue (AT) interleukin (IL)-18 mRNA expression and that AT IL-18 mRNA expression is related to insulin......: AT IL-18 mRNA content and plasma IL-18 concentration were higher (p insulin resistance. While acute exercise did not affect IL-18 mRNA expression...... at the studied time-points, exercise training reduced AT IL-18 mRNA content by 20% in both sexes. DISCUSSION: Because obesity and insulin resistance were associated with elevated AT IL-18 mRNA and plasma IL-18 levels, the training-induced lowering of AT IL-18 mRNA content may contribute to the beneficial effects...

  3. [Change in acylneuraminic acid content of T-lymphocytes and in plasma in breast cancer].

    Science.gov (United States)

    Stickl, H; Huber, W; Faillard, H; Becker, A; Holzhauser, R; Graeff, H

    1991-01-04

    Increased sialic acid levels reflecting tumor burden are found on the surface of T-lymphocytes and in the plasma of patients with carcinoma of the mammary gland. The data of the determinations of sialic acid content and distribution on T-cells, using microanalytical methods such as HPLC and a colorimetric test, show that the total sialic acid content is increased by about 60% and that nearly 80-90% of the sialic acids consist of N-acetyl-9-O-acetyl-neuraminic acid, in comparison to the healthy controls (not containing O-acetylated neuraminic acid). Investigations on lymphocytes of malignant melanoma patients show similar changes of sialic acid content and distribution on the cell surface. Increased sialic acid levels are also found in the plasma of patients with cancer but no O-acetylated derivative can be found. Furthermore the examinations show that the separation of the T-lymphocytes from the total lymphocyte fraction is not required. Determination of sialic acids in the total lymphocyte fraction can be a simplification in carrying out further diagnostic investigations. A high level of sialic acids as "antirecognition factor" seems to be not only a marker of tumor cells but also an attribute of T-lymphocytes, involved in the defence against the malignoma (malignant melanoma, breast cancer). Considering the possible contribution of sialic acid to the immunoregulatory protective mechanism during the first stage of pregnancy, sialic acid content and distribution on T-cells of pregnant women are investigated. Both an increase and a change in the distribution of sialic acids can be excluded.

  4. Increased tartrate-resistant acid phosphatase (TRAP expression in malignant breast, ovarian and melanoma tissue: an investigational study

    Directory of Open Access Journals (Sweden)

    Eck M

    2006-07-01

    Full Text Available Abstract Background Tartrate-resistant acid phosphatase (TRAP is a metalloprotein enzyme that belongs to the acid phosphatases and is known to be expressed by osteoclasts. It has already been investigated as a marker of bone metastases in cancer patients. In this study, which examined the value of serum TRAP concentrations as a marker of bone disease in breast cancer patients, we observed high concentrations of TRAP even in patients without bone metastases. To elucidate this phenomenon, we examined the expression of TRAP in breast cancer cells and the cells of several other malignancies. Methods TRAP concentrations in the serum of tumor patients were determined by ELISA. The expression of TRAP in breast, ovarian, and cervical cancer and malignant melanoma was analyzed by immunohistochemistry. RT-PCR and immunocytology were used to evaluate TRAP expression in cultured tumor cells. Results A marked increase in serum TRAP concentrations was observed in patients with breast and ovarian cancer, regardless of the presence or absence of bone disease. TRAP expression was found in breast and ovarian cancers and malignant melanoma, while cervical cancer showed only minimal expression of TRAP. Expression of TRAP was absent in benign tissue or was much less marked than in the corresponding malignant tissue. TRAP expression was also demonstrated in cultured primary cancer cells and in commercially available cell lines. Conclusion Overexpression of TRAP was detected in the cells of various different tumors. TRAP might be useful as a marker of progression of malignant disease. It could also be a potential target for future cancer therapies.

  5. Recipient Vessel Selection in Immediate Breast Reconstruction with Free Abdominal Tissue Transfer after Nipple-Sparing Mastectomy

    Directory of Open Access Journals (Sweden)

    Sung Jun Yang

    2012-05-01

    Full Text Available BackgroundNipple-sparing mastectomy (NSM is gaining popularity due to its superior aesthetic results. When reconstructing the breast with free abdominal tissue transfer, we must readdress the recipient vessel, because NSM can cause difficulty in access to the chest vessel.MethodsBetween June 2006 and March 2011, a total of 92 women underwent NSM with free abdominal tissue transfer. A lateral oblique incision was used for the nipple-sparing mastectomy. For recipient vessels, the internal mammary vessels were chosen if the mastectomy flap did not block access to the vessels. If it did, the thoracodorsal vessels were used. Age, degree of breast ptosis, weight of the mastectomy specimen, and related complications of the internal mammary vessel group and the thoracodorsal vessel group were compared.ResultsThoracodorsal vessels were used as recipient vessels in 59 cases, and internal mammary vessels in 33 cases including 4 cases with perforators of the internal mammary vessels. Breast reconstruction was successful in all cases except one case involving a total flap failure, which was replaced by a silicone gel implant. The internal mammary group and the thoracodorsal group were similar in terms of age, height, breast weight, and degree of ptosis. The flap related complications such as flap loss and take-back operation rates were not significantly different between the two groups. The rate of nipple necrosis was higher in the internal mammary group.ConclusionsThe thoracodorsal vessels could produce comparable outcomes in breast reconstruction after nipple-sparing mastectomies. If access to internal mammary vessels is difficult, the thoracodorsal vessel can be a better choice.

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

    Science.gov (United States)

    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.

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

    OpenAIRE

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

    2008-01-01

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

  8. Effect of implant vs. tissue reconstruction on cancer specific survival varies by axillary lymph node status in breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Qian Ouyang

    Full Text Available To compare the breast cancer-specific survival (BCSS between patients who underwent tissue or implant reconstruction after mastectomy.We used the database from Surveillance, Epidemiology, and End Results (SEER registries and compared the BCSS between patients who underwent tissue and implant reconstruction after mastectomy. Cox-regression models were fitted, adjusting for known clinicopathological features. The interaction between the reconstruction types (tissue/implant and nodal status (N-stage was investigated.A total of 6,426 patients with a median age of 50 years were included. With a median follow up of 100 months, the 10-year cumulative BCSS and non-BCSS were 85.1% and 95.4%, respectively. Patients who underwent tissue reconstruction had tumors with a higher T-stage, N-stage, and tumor grade and tended to be ER/PR-negative compared to those who received implant reconstruction. In univariate analysis, implant-reconstruction was associated with a 2.4% increase (P = 0.003 in the BCSS compared with tissue-reconstruction. After adjusting for significant risk factors of the BCSS (suggested by univariate analysis and stratifying based on the N-stage, there was only an association between the reconstruction type and the BCSS for the N2-3 patients (10-year BCSS of implant vs. tissue-reconstruction: 68.7% and 59.0%, P = 0.004. The 10-year BCSS rates of implant vs. tissue-reconstruction were 91.7% and 91.8% in N0 patients (P>0.05 and 84.5% and 84.4% in N1 patients (P>0.05, respectively.The implant (vs. tissue reconstruction after mastectomy was associated with an improved BCSS in N2-3 breast cancer patients but not in N0-1 patients. A well-designed, prospective study is needed to further confirm these findings.

  9. Time- and space-resolved spectroscopic characterization of laser-induced swine muscle tissue plasma

    Energy Technology Data Exchange (ETDEWEB)

    Camacho, J.J. [Departamento de Química-Física Aplicada, Facultad de Ciencias, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid (Spain); Diaz, L., E-mail: luis.diaz@csic.es [Instituto de Estructura de la Materia, CFMAC, CSIC, Serrano 121, 28006 Madrid (Spain); Martinez-Ramirez, S. [Instituto de Estructura de la Materia, CFMAC, CSIC, Serrano 121, 28006 Madrid (Spain); Caceres, J.O. [Departamento de Química Analítica, Facultad de Ciencias Químicas, Universidad Complutense, Cuidad Universitaria, 28040 Madrid (Spain)

    2015-09-01

    The spatial-temporal evolution of muscle tissue sample plasma induced by a high-power transversely excited atmospheric (TEA) CO{sub 2} pulsed laser at vacuum conditions (0.1–0.01 Pa) has been investigated using high-resolution optical emission spectroscopy (OES) and imaging methods. The induced plasma shows mainly electronically excited neutral Na, K, C, Mg, H, Ca, N and O atoms, ionized C{sup +}, C{sup 2+}, C{sup 3+}, Mg{sup +}, Mg{sup 2+}, N{sup +}, N{sup 2+}, Ca{sup +}, O{sup +} and O{sup 2+} species and molecular band systems of CN(B{sup 2}Σ{sup +}–X{sup 2}Σ{sup +}), C{sub 2}(d{sup 3}Π{sub g}–a{sup 3}Π{sub u}), CH(B{sup 2}Σ{sup −}–X{sup 2}Π; A{sup 2}Δ–X{sup 2}Π), NH(A{sup 3}Π–X{sup 3}Σ{sup −}), OH(A{sup 2}Σ{sup +}–X{sup 2} Σ{sup +}), and CaOH(B{sup 2}Σ{sup +}–X{sup 2}Σ{sup +}; A{sup 2}Π–X{sup 2}Σ{sup +}). Time-resolved two-dimensional emission spectroscopy is used to study the expanded distribution of different species ejected during ablation. Spatial and temporal variations of different atoms and ionic excited species are reported. Plasma parameters such as electron density and temperature were measured from the spatio-temporal analysis of different species. Average velocities of some plasma species were estimated. - Highlights: • LIBS of swine muscle tissue sample generated by CO{sub 2} laser pulses has been done for the first time. • Average velocities of some plasma species have been calculated from spatial and temporally resolved 2D OES images. • Electron density (~ 9 × 10{sup 17} cm{sup -3}) has been studied with spatial and temporal resolution. • Temporal evolution of the plasma temperature has been calculated by means of Boltzmann plots.

  10. Comparing paraffined and deparaffinized breast cancer tissue samples and an analysis of Raman spectroscopy and infrared methods

    Science.gov (United States)

    Depciuch, J.; Kaznowska, E.; Szmuc, K.; Zawlik, I.; Cholewa, M.; Heraud, P.; Cebulski, J.

    2016-05-01

    Breast cancer makes up a quarter of all cancer in women, which is why research into new diagnostic methods and sample preparations need to be developed at an accelerated pace. Researchers are looking for diagnostic tools to detect when an individual has cancer cells and use that information to see what measurements and approaches can be used to take further diagnostic steps. The most common method of sample preparation is the imbibing of tumor tissue in paraffin, which can produce a background for spectroscopic measurements in the range of 500-3500 cm-1. In this study we demonstrated that proper preparation of paraffin-embedded specimens and the measurement methodology can eliminate paraffin vibration, as was done in the work Depciuch et al. 2015. Thanks to this spectroscopic technique there may become a reliable and accurate method of diagnosing breast cancer based on the evidence found from the prepared samples. The study compared the results obtained through Raman spectroscopy and FTIR (Fourier Transform Infrared) measurements of healthy and cancerous breast tissues that were either embedded in paraffin or deparaffinized. The resulting spectrum and accurate analysis led to the conclusion that the appropriate measurement of the background and the elimination of peaks from the paraffin had the greatest impact on the reliability of results. Furthermore, after the accurate, detailed studies FTIR and Raman spectroscopy on samples of breast tissue that were deparaffinized or embedded in paraffin, including a complete analysis of the peak after transformation Kramers-Kröning (KK), it was found that sample preparation did not affect the result obtained by measuring the reflectance in the mid-infrared range, and that this only had a minimal effect relating to the intensity obtained by the measurement of the Raman peak. Only in special cases, when Raman spectroscopic methods are used for research to find the peculiarities of the spectra, are deparaffinization recommended

  11. Patient-subjective cosmetic outcomes following the varying stages of tissue expander breast reconstruction: the importance of completion.

    Science.gov (United States)

    Buck, Donald W; Shenaq, Deana; Heyer, Kamaldeep; Kato, Caroline; Kim, John Y S

    2010-12-01

    Tissue expander breast reconstruction consists of three major surgical steps: placement of the expander after mastectomy, exchange of the expander for an implant, and nipple-areola complex reconstruction. The evolution of patient satisfaction throughout this process has not been evaluated. Here we performed a stratified analysis of patient-subjective cosmetic outcomes during the stages of breast reconstruction. Twenty-eight consecutive tissue expander-implant reconstructions were performed by the senior author using human acellular dermis. Cosmetic outcomes were assessed after each reconstructive stage using a validated Breast Evaluation Questionnaire consisting of questions related to breast size, shape and firmness in three separate contexts: intimate or sexual activities, leisure or social activities, and professional or job-related activities. Eighteen patients underwent unilateral reconstruction, while 10 underwent bilateral reconstruction. Satisfaction scores were statistically higher following Stage I and II procedures for bilateral reconstructions. For unilateral reconstructions, there was a statistically significant elevation in scores following Stage II. The addition of nipple-areola reconstruction resulted in the highest scores for both unilateral and bilateral reconstructions. These score elevations were significant (p reconstructions and as such, the significant differences in scores between unilateral and bilateral cohorts after stages I and II were nearly eliminated after completion of the entire reconstructive process. Satisfaction with tissue expander reconstruction is significantly affected by the patients' stage during the reconstructive process. Completion of all three stages, including nipple-areolar complex reconstruction, achieves maximal patient satisfaction. For unilateral reconstructions, completion of the entire reconstructive process, including contralateral symmetry procedures and nipple-areolar complex reconstruction, results in

  12. A complex 3D human tissue culture system based on mammary stromal cells and silk scaffolds for modeling breast morphogenesis and function.

    Science.gov (United States)

    Wang, Xiuli; Sun, Lin; Maffini, Maricel V; Soto, Ana; Sonnenschein, Carlos; Kaplan, David L

    2010-05-01

    Epithelial-stromal interactions play a crucial role in normal embryonic development and carcinogenesis of the human breast while the underlying mechanisms of these events remain poorly understood. To address this issue, we constructed a physiologically relevant, three-dimensional (3D) culture surrogate of complex human breast tissue that included a tri-culture system made up of human mammary epithelial cells (MCF10A), human fibroblasts and adipocytes, i.e., the two dominant breast stromal cell types, in a Matrigel/collagen mixture on porous silk protein scaffolds. The presence of stromal cells inhibited MCF10A cell proliferation and induced both alveolar and ductal morphogenesis and enhanced casein expression. In contrast to the immature polarity exhibited by co-cultures with either fibroblasts or adipocytes, the alveolar structures formed by the tri-cultures exhibited proper polarity similar to that observed in breast tissue in vivo. Only alveolar structures with reverted polarity were observed in MCF10A monocultures. Consistent with their phenotypic appearance, more functional differentiation of epithelial cells was also observed in the tri-cultures, where casein alpha- and -beta mRNA expression was significantly increased. This in vitro tri-culture breast tissue system sustained on silk scaffold effectively represents a more physiologically relevant 3D microenvironment for mammary epithelial cells and stromal cells than either co-cultures or monocultures. This experimental model provides an important first step for bioengineering an informative human breast tissue system, with which to study normal breast morphogenesis and neoplastic transformation.

  13. Determination of Epimedin B in Rat Plasma and Tissue by LC-MS/MS: Application in Pharmacokinetic and Tissue Distribution Studies

    Directory of Open Access Journals (Sweden)

    Qianru Feng

    2017-01-01

    Full Text Available A simple, sensitive, and specific liquid chromatography tandem mass-spectrometric method was developed and validated for the determination of epimedin B in rat plasma and tissue samples. After being processed with a protein precipitation method, these samples were separated on an Agilent Eclipse XDB-C18 column with an isocratic mobile phase consisting of acetonitrile and 0.1% formic acid aqueous solution (32 : 68, v/v. The calibration curve of epimedin B was linear over the concentration range from 1 to 500 ng/mL in plasma and tissue homogenate. The method was then applied to pharmacokinetic and tissue distribution studies after a single oral administration of Herba Epimedii extract to SD rats. Results showed that epimedin B reached the plasma peak concentration at 0.4 h and the terminal elimination half-life was 1.6 h in rat plasma, and the plasma area under the curve from time zero to infinity (AUC0–∞ was 14.35 μg/L·h. The concentration distribution of epimedin B in rat tissue was in the following order: liver > ovary > womb > lung > kidney > spleen > heart > brain, indicating that the compound could be widely distributed in rat, and the reproductive system may be the principal target of epimedin B for female rat.

  14. Human adipose tissue-derived stromal/stem cells promote migration and early metastasis of triple negative breast cancer xenografts.

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    Brian G Rowan

    Full Text Available BACKGROUND: Fat grafting is used to restore breast defects after surgical resection of breast tumors. Supplementing fat grafts with adipose tissue-derived stromal/stem cells (ASCs is proposed to improve the regenerative/restorative ability of the graft and retention. However, long term safety for ASC grafting in proximity of residual breast cancer cells is unknown. The objective of this study was to determine the impact of human ASCs derived from abdominal lipoaspirates of three donors, on a human breast cancer model that exhibits early metastasis. METHODOLOGY/PRINCIPAL FINDINGS: Human MDA-MB-231 breast cancer cells represents "triple negative" breast cancer that exhibits early micrometastasis to multiple mouse organs [1]. Human ASCs were derived from abdominal adipose tissue from three