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Sample records for malignant breast tissue

  1. The Microbiome of Aseptically Collected Human Breast Tissue in Benign and Malignant Disease

    PubMed Central

    Hieken, Tina J.; Chen, Jun; Hoskin, Tanya L.; Walther-Antonio, Marina; Johnson, Stephen; Ramaker, Sheri; Xiao, Jian; Radisky, Derek C.; Knutson, Keith L.; Kalari, Krishna R.; Yao, Janet Z.; Baddour, Larry M.; Chia, Nicholas; Degnim, Amy C.

    2016-01-01

    Globally breast cancer is the leading cause of cancer death among women. The breast consists of epithelium, stroma and a mucosal immune system that make up a complex microenvironment. Growing awareness of the role of microbes in the microenvironment recently has led to a series of findings important for human health. The microbiome has been implicated in cancer development and progression at a variety of body sites including stomach, colon, liver, lung, and skin. In this study, we assessed breast tissue microbial signatures in intraoperatively obtained samples using 16S rDNA hypervariable tag sequencing. Our results indicate a distinct breast tissue microbiome that is different from the microbiota of breast skin tissue, breast skin swabs, and buccal swabs. Furthermore, we identify distinct microbial communities in breast tissues from women with cancer as compared to women with benign breast disease. Malignancy correlated with enrichment in taxa of lower abundance including the genera Fusobacterium, Atopobium, Gluconacetobacter, Hydrogenophaga and Lactobacillus. This work confirms the existence of a distinct breast microbiome and differences between the breast tissue microbiome in benign and malignant disease. These data provide a foundation for future investigation on the role of the breast microbiome in breast carcinogenesis and breast cancer prevention. PMID:27485780

  2. The Microbiome of Aseptically Collected Human Breast Tissue in Benign and Malignant Disease.

    PubMed

    Hieken, Tina J; Chen, Jun; Hoskin, Tanya L; Walther-Antonio, Marina; Johnson, Stephen; Ramaker, Sheri; Xiao, Jian; Radisky, Derek C; Knutson, Keith L; Kalari, Krishna R; Yao, Janet Z; Baddour, Larry M; Chia, Nicholas; Degnim, Amy C

    2016-01-01

    Globally breast cancer is the leading cause of cancer death among women. The breast consists of epithelium, stroma and a mucosal immune system that make up a complex microenvironment. Growing awareness of the role of microbes in the microenvironment recently has led to a series of findings important for human health. The microbiome has been implicated in cancer development and progression at a variety of body sites including stomach, colon, liver, lung, and skin. In this study, we assessed breast tissue microbial signatures in intraoperatively obtained samples using 16S rDNA hypervariable tag sequencing. Our results indicate a distinct breast tissue microbiome that is different from the microbiota of breast skin tissue, breast skin swabs, and buccal swabs. Furthermore, we identify distinct microbial communities in breast tissues from women with cancer as compared to women with benign breast disease. Malignancy correlated with enrichment in taxa of lower abundance including the genera Fusobacterium, Atopobium, Gluconacetobacter, Hydrogenophaga and Lactobacillus. This work confirms the existence of a distinct breast microbiome and differences between the breast tissue microbiome in benign and malignant disease. These data provide a foundation for future investigation on the role of the breast microbiome in breast carcinogenesis and breast cancer prevention. PMID:27485780

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

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2006-06-01

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

  5. Mapping the cellular and molecular heterogeneity of normal and malignant breast tissues and cultured cell lines

    PubMed Central

    2010-01-01

    Introduction Normal and neoplastic breast tissues are comprised of heterogeneous populations of epithelial cells exhibiting various degrees of maturation and differentiation. While cultured cell lines have been derived from both normal and malignant tissues, it remains unclear to what extent they retain similar levels of differentiation and heterogeneity as that found within breast tissues. Methods We used 12 reduction mammoplasty tissues, 15 primary breast cancer tissues, and 20 human breast epithelial cell lines (16 cancer lines, 4 normal lines) to perform flow cytometry for CD44, CD24, epithelial cell adhesion molecule (EpCAM), and CD49f expression, as well as immunohistochemistry, and in vivo tumor xenograft formation studies to extensively analyze the molecular and cellular characteristics of breast epithelial cell lineages. Results Human breast tissues contain four distinguishable epithelial differentiation states (two luminal phenotypes and two basal phenotypes) that differ on the basis of CD24, EpCAM and CD49f expression. Primary human breast cancer tissues also contain these four cellular states, but in altered proportions compared to normal tissues. In contrast, cultured cancer cell lines are enriched for rare basal and mesenchymal epithelial phenotypes, which are normally present in small numbers within human tissues. Similarly, cultured normal human mammary epithelial cell lines are enriched for rare basal and mesenchymal phenotypes that represent a minor fraction of cells within reduction mammoplasty tissues. Furthermore, although normal human mammary epithelial cell lines exhibit features of bi-potent progenitor cells they are unable to differentiate into mature luminal breast epithelial cells under standard culture conditions. Conclusions As a group breast cancer cell lines represent the heterogeneity of human breast tumors, but individually they exhibit increased lineage-restricted profiles that fall short of truly representing the intratumoral

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

    PubMed

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

    2006-03-01

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

  7. Nuclear magnetic resonance for the differentiation of benign and malignant breast tissues and axillary lymph nodes.

    PubMed Central

    Fossel, E T; Brodsky, G; deLayre, J L; Wilson, R E

    1983-01-01

    We have utilized proton T1 (spin-lattice relaxation time) values of Nuclear Magnetic Resonance to study 110 tissue samples obtained from 11 mastectomy specimens. Samples of 1 cm3 from primary tumor sites, nipples, and other breast quadrants, as well as intact lymph nodes were studied and then histologically scored for the presence or absence of carcinoma and, if present, whether it was an isolated microscopic focus (micro). Of 54 samples of breast tissue, 12 contained carcinoma, 5 micro: of 45 lymph nodes, 15 contained metastatic carcinoma, 2 micro; of the 11 nipples, 2 had carcinoma, both micro. For the malignant samples (excluding micro) mean T1 value was 0.47 +/- 0.07 sec, (range 0.39-0.79 sec). For the 72 benign samples (excluding nipple) mean T1 value was 0.26 +/- 0.03 sec (range 0.14-0.36 sec). The 13 tumor-bearing nodes had a mean T1 value of 0.47 +/- 0.03 sec (range 0.40-0.63 sec); mean for the benign nodes was 0.26 +/- 0.007 sec (range 0.19-0.35 sec). The differences were highly significant in each case (p less than 0.001). For micro examples, T1 values were at malignancy threshold levels or just below, except for nipple tissues, where discrimination was poor. For the 20 other malignant samples, there was no correlation between T1 value and the per cent of sample containing malignancy. PMID:6625722

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

    PubMed

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

    2004-08-01

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

  9. Intraoperative diagnosis of benign and malignant breast tissues by fourier transform infrared spectroscopy and support vector machine classification

    PubMed Central

    Tian, Peirong; Zhang, Weitao; Zhao, Hongmei; Lei, Yutao; Cui, Long; Wang, Wei; Li, Qingbo; Zhu, Qing; Zhang, Yuanfu; Xu, Zhi

    2015-01-01

    Background: Fourier transform infrared (FTIR) spectroscopy has shown its unique advantages in distinguishing cancerous tissue from normal one. The aim of this study was to establish a quick and accurate diagnostic method of FTIR spectroscopy to differentiate malignancies from benign breast tissues intraoperatively. Materials and methods: In this study, a total of 100 breast tissue samples obtained from 100 patients were taken on surgery. All tissue samples were scanned for spectra intraoperatively before being processed for histopathological diagnosis. Standard normal variate (SNV) method was adopted to reduce scatter effects. Support vector machine (SVM) classification was used to discriminate spectra between malignant and benign breast tissues. Leave-one-out cross validation (LOOCV) was used to evaluate the discrimination. Results: According to histopathological examination, 50 cases were diagnosed as fibroadenoma and 50 cases as invasive ductal carcinoma. The results of SVM algorithm showed that the sensitivity, specificity and accuracy rate of this method are 90.0%, 98.0% and 94.0%, respectively. Conclusions: FTIR spectroscopy technique in combination with SVM classification could be an accurate, rapid and objective tool to differentiate malignant from benign tumors during operation. Our studies establish the feasibility of FTIR spectroscopy with chemometrics method to guide surgeons during the surgery as an effective supplement for pathological diagnosis on frozen section. PMID:25785083

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

    NASA Astrophysics Data System (ADS)

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

    2004-04-01

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

  11. Potential of Diffusion-Weighted Imaging in the Characterization of Malignant, Benign, and Healthy Breast Tissues and Molecular Subtypes of Breast Cancer

    PubMed Central

    Sharma, Uma; Sah, Rani G.; Agarwal, Khushbu; Parshad, Rajinder; Seenu, Vurthaluru; Mathur, Sandeep R.; Hari, Smriti; Jagannathan, Naranamangalam R.

    2016-01-01

    The role of apparent diffusion coefficient (ADC) in the diagnosis of breast cancer and its association with molecular biomarkers was investigated in 259 patients with breast cancer, 67 with benign pathology, and 54 healthy volunteers using diffusion-weighted imaging (DWI) at 1.5 T. In 59 breast cancer patients, dynamic contrast-enhanced MRI (DCEMRI) was also acquired. Mean ADC of malignant lesions was significantly lower (1.02 ± 0.17 × 10−3 mm2/s) compared to benign (1.57 ± 0.26 × 10−3 mm2/s) and healthy (1.78 ± 0.13 × 10−3 mm2/s) breast tissues. A cutoff ADC value of 1.23 × 10−3 mm2/s (sensitivity 92.5%; specificity 91.1%; area under the curve 0.96) to differentiate malignant from benign diseases was arrived by receiver operating curve analysis. In 10/59 breast cancer patients, indeterminate DCE curve was seen, while their ADC value was indicative of malignancy, implying the potential of the addition of DWI in increasing the specificity of DCEMRI data. Further, the association of ADC with tumor volume, stage, hormonal receptors [estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor (HER2)], and menopausal status was investigated. A significant difference was seen in tumor volume between breast cancer patients of stages IIA and IIIA, IIB and IIIA, and IIB and III (B + C), respectively (P < 0.05). Patients with early breast cancer (n = 52) had significantly lower ADC and tumor volume than those with locally advanced breast cancer (n = 207). No association was found in ADC and tumor volume with the menopausal status. Breast cancers with ER−, PR−, and triple-negative (TN) status showed a significantly larger tumor volume compared to ER+, PR+, and non-triple-negative (nTN) cancers, respectively. Also, TN tumors showed a significantly higher ADC compared to ER+, PR+, and nTN cancers. Patients with ER− and TN cancers were younger than those with ER+ and nTN cancers

  12. Potential of Diffusion-Weighted Imaging in the Characterization of Malignant, Benign, and Healthy Breast Tissues and Molecular Subtypes of Breast Cancer.

    PubMed

    Sharma, Uma; Sah, Rani G; Agarwal, Khushbu; Parshad, Rajinder; Seenu, Vurthaluru; Mathur, Sandeep R; Hari, Smriti; Jagannathan, Naranamangalam R

    2016-01-01

    The role of apparent diffusion coefficient (ADC) in the diagnosis of breast cancer and its association with molecular biomarkers was investigated in 259 patients with breast cancer, 67 with benign pathology, and 54 healthy volunteers using diffusion-weighted imaging (DWI) at 1.5 T. In 59 breast cancer patients, dynamic contrast-enhanced MRI (DCEMRI) was also acquired. Mean ADC of malignant lesions was significantly lower (1.02 ± 0.17 × 10(-3) mm(2)/s) compared to benign (1.57 ± 0.26 × 10(-3) mm(2)/s) and healthy (1.78 ± 0.13 × 10(-3) mm(2)/s) breast tissues. A cutoff ADC value of 1.23 × 10(-3) mm(2)/s (sensitivity 92.5%; specificity 91.1%; area under the curve 0.96) to differentiate malignant from benign diseases was arrived by receiver operating curve analysis. In 10/59 breast cancer patients, indeterminate DCE curve was seen, while their ADC value was indicative of malignancy, implying the potential of the addition of DWI in increasing the specificity of DCEMRI data. Further, the association of ADC with tumor volume, stage, hormonal receptors [estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor (HER2)], and menopausal status was investigated. A significant difference was seen in tumor volume between breast cancer patients of stages IIA and IIIA, IIB and IIIA, and IIB and III (B + C), respectively (P < 0.05). Patients with early breast cancer (n = 52) had significantly lower ADC and tumor volume than those with locally advanced breast cancer (n = 207). No association was found in ADC and tumor volume with the menopausal status. Breast cancers with ER-, PR-, and triple-negative (TN) status showed a significantly larger tumor volume compared to ER+, PR+, and non-triple-negative (nTN) cancers, respectively. Also, TN tumors showed a significantly higher ADC compared to ER+, PR+, and nTN cancers. Patients with ER- and TN cancers were younger than those with ER+ and n

  13. Low or undetectable TPO receptor expression in malignant tissue and cell lines derived from breast, lung, and ovarian tumors

    PubMed Central

    2012-01-01

    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 megakaryocyte precursors. PMID

  14. Enhanced expression of polysialic acid correlates with malignant phenotype in breast cancer cell lines and clinical tissue samples.

    PubMed

    Wang, Xin; Li, Xiang; Zeng, Ying-Nan; He, Fa; Yang, Xiao-Min; Guan, Feng

    2016-01-01

    Polysialic acid (PSA) is highly expressed during embryonic development, but barely expressed during postnatal development, and may be 're-expressed' in cancer tissues. In this study, motility and migration assays were performed to compare the changes in cell behavior between non-malignant and maligant cells. Next, the expression levels of PSA were evaluated in 4 human and mouse normal breast or breast cancer (BC) cell lines using 1,2-diamino-4,5-methylenedioxybenzene-labeling HPLC technology, as well as in human clinical BC tissue samples. PSA expression was significantly higher in malignant cells (where it appeared to facilitate cell migration and motility) than in non-malignant cells. Enhanced PSA expression levels were also observed during epithelial-mesenchymal transition (EMT), a leading cause of cancer cell metastasis, which was induced in the NMuMG and MCF10A cells by treatment with transforming growth factor-β1 (TGF-β1). An increased PSA expression also correlated with the disease stage in the patients with BC (P<0.0001). Using RT-qPCR, we found that polysialyltransferase ST8SiaIV (PST) and polysialyltransferase ST8SiaII (STX), which are responsible for PSA synthesis, were differently expressed in the tested BC samples. However, PST, but not STX, was re-expressed in 14 out of 20 clinical BC samples. The findings of the present study indicate that the pathophysiology of BC involves the aberrant regulation of PSA expression and PST gene expression. PMID:26530860

  15. Coherent time-reversal microwave imaging for the detection and localization of breast tissue malignancies

    NASA Astrophysics Data System (ADS)

    Hossain, Md. Delwar; Mohan, Ananda Sanagavarapu

    2015-02-01

    This paper deals with the coherent processing of time-reversal operator for microwave imaging in the frequency domain. In frequency domain time-reversal imaging approach, images obtained for different frequency bins over ultrawideband are incoherently processed. In highly dense and cluttered medium, the signal subspace over each narrow frequency bin varies from that obtained using the complete ultrawideband. As a result, the detection and localization from noncoherent imaging approach is often inconclusive. In order to improve the stability of time-reversal microwave imaging, we propose coherent processing using novel focusing matrix approach. The proposed focusing matrix makes possible the time-reversal imaging technique to coherently process each frequency bin to yield a consistent signal subspace. The performance of coherent focusing is investigated when combined with time-reversal robust Capon beamformer (TR-RCB). We have used numerical experiments on breast cancer detection using finite difference time domain employing anatomically realistic numerical breast phantoms that contain varying amounts of dense fibroglandular tissue content. The imaging results indicate that the proposed coherent-TR-RCB could overcome the limitations of time-reversal imaging in a highly heterogeneous and cluttered medium.

  16. Development and Feasibility Testing of Image-Guided Minimally Invasive Tissue for Diagnosis Treatment of Benign and Malignant Breast Disease

    NASA Technical Reports Server (NTRS)

    Jeffrey, Stefanie S.

    1999-01-01

    Dr. Robert Mah and Dr. Stefanie Jeffrey worked on the development of the NASA Smart Probe in its application as a device to measure and interpret physiologic and image-based parameters of breast tissue. To date the following has been achieved: 1 . Choice of candidate sensors to be tested in breast tissue. 2. Preliminary designs for probe tip, specifically use of different tip shapes, cutting edges, and sensor configuration. 3. Design of sonographic guidance system. 4. Design of data extraction and analysis tool using scanned information of images of the breast tissue to provide a higher dimension of information for breast tissue characterization and interpretation. 5. Initial ex-vivo (fruit and tofu) and in-vivo (rodent) testing to confirm unique substance and tissue characterization by the Smart Probe software.

  17. Malignant adenomyoepithelioma of the breast: a review.

    PubMed

    Ahmadi, Nasrollah; Negahban, Shahrzad; Aledavood, Azita; Daneshbod, Khosrow; Daneshbod, Yahya

    2015-01-01

    Malignant adenomyoepithelioma (MAME) of the breast is a rare lesion characterized by dual population of epithelial and myoepithelial cells which one or both components show malignant features. We report a case of MAME of the breast in a 46-year-old woman diagnosed by fine-needle aspiration with extensive review of the literature. Classification, clinical presentation, cyto-pathologic, and immunohistochemical features are described. This lesion showed both malignant components of epithelial and myoepithelial cells in cytology and histology. The malignancy was convincingly supported by high mitotic figures, pleomorphism, and invasion in tissue sections. This review of MAMEs showed that cyto-histologic diagnosis is difficult and should be supported by immunohistochemical study. PMID:25772218

  18. Overexpression of seven in absentia homolog 2 protein in human breast cancer tissues is associated with the promotion of tumor cell malignant behavior in in vitro.

    PubMed

    Sun, Jie; Zhang, Xiaojuan; Han, Yanchun; Zhen, Juan; Meng, Yuan; Song, Min

    2016-09-01

    Seven in absentia homolog 2 (SIAH2), a homologue of Drosophila seven in absentia (Sina), has emerged as an oncogene and plays important roles in cancer development and progression. This study further assessed the role of SIAH2 in breast cancer and the underlying molecular events. The data showed that SIAH2 protein was overexpressed in invasive breast cancer (IBC) compared to the expression noted in normal or ductal carcinoma in situ (DCIS) tissues, expression of which is associated with malignant behaviors. SIAH2 may function differently in different molecular subtypes (e.g., luminal- vs. basal-like type) of breast cancer. Manipulation of SIAH2 expression led to a 'cross-talk' of the ERK and PI3K pathway, which could be one of the mechanisms by which SIAH2 regulates viability, apoptosis, and invasion capacity in these breast cancer cell lines. PMID:27459914

  19. Quantitative expression analysis and study of the novel human kallikrein-related peptidase 14 gene (KLK14) in malignant and benign breast tissues.

    PubMed

    Papachristopoulou, Georgia; Avgeris, Margaritis; Charlaftis, Antonios; Scorilas, Andreas

    2011-01-01

    Human kallikrein-related peptidase 14 gene (KLK14) is regulated by androgens and progestins. This gene is expressed in the central nervous system and endocrine tissues such as the breast, prostate and ovary. The differential KLK14 mRNA expression levels are related to several human neoplasias, among them breast cancer. The aim of this study was to analyse the KLK14 expression in breast tissues and to investigate its differential diagnostic and prognostic value in the mammary carcinomas. For this purpose, we isolated total RNA from 70 malignant and 33 benign specimens. After testing RNA quality, we synthesised cDNA by reverse transcription and applied a highly sensitive quantitative real-time PCR (qRT-PCR) method for KLK14 mRNA quantification using the SYBR Green® chemistry. HPRT1 was used as a reference gene and the BT20 breast cancer cell line as a calibrator. Relative quantification analysis was performed using the comparative CT method 2-ΔΔCT. KLK14 expression was detected in both types of breast tumours. However, a statistically significant increase of the KLK14 mRNA level was observed in the malignant, compared to the benign tumour samples (p<0.001), highlighting its value in discriminating these breast lesions. Elevated KLK14 expression profiles were associated with higher tumour grade (p=0.043) and size (p=0.007) in cancerous samples. Furthermore, KLK14 mRNA expression showed negative correlation in a statistically significant manner with estrogen receptor status (p=0.024). In accordance with logistic regression models (p=0.012) and receiver-operating-characteristics analysis (p<0.001), KLK14 gene expression could be evaluated as a putative independent diagnostic biomarker in breast tumour biopsies. PMID:21057706

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

    PubMed Central

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

    2016-01-01

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

  1. Rare Malignant Tumors of the Breast

    PubMed Central

    Miller, Trevor; Albarracin, Constance; Carkaci, Selin; Whitman, Gary J; Adrada, Beatriz E

    2015-01-01

    While the more common forms of breast cancer are well understood and recognized, there are many important rare malignancies that are less appreciated. Many of these cancers have imaging findings that, when understood, help to formulate a more educated differential diagnosis. In this article, the clinical features, imaging, and pathologic findings of rare breast malignancies will be discussed. PMID:26664775

  2. Infrared absorption spectra of human malignant tumor tissues

    NASA Astrophysics Data System (ADS)

    Skornyakov, I. V.; Tolstorozhev, G. B.; Butra, V. A.

    2008-05-01

    We used infrared spectroscopy methods to study the molecular structure of tissues from human organs removed during surgery. The IR spectra of the surgical material from breast, thyroid, and lung are compared with data from histological examination. We show that in malignant neoplasms, a change occurs in the hydrogen bonds of protein macromolecules found in the tissue of the studied organs. We identify the spectral signs of malignant pathology.

  3. Optical discrimination between malignant and benign breast lesions

    NASA Astrophysics Data System (ADS)

    Quarto, Giovanna; Pifferi, Antonio; Cubeddu, Rinaldo; Ieva, Francesca; Paganoni, Anna Maria; Abbate, Francesca; Cassano, Enrico; Taroni, Paola

    2015-07-01

    Time domain multi-wavelength (635 to 1060 nm) optical mammography was performed on 82 subjects with breast lesions (45 malignant and 38 benign lesions). A perturbative approach based on the high-order calculation of the pathlength of photons inside the lesion was applied to estimate differences between lesion and average healthy tissue of the same breast in terms of: i) absorption properties, and ii) concentration of the major tissue constituents (oxy- and deoxy-hemoglobin, water, lipid and collagen). The absorption difference Δμa between lesion and healthy tissue is significantly different for malignant vs. benign lesions at all wavelengths. Logistic regression fitted to the absorption data identifies 975 nm as the key wavelength to discriminate malignant from benign lesions. When the difference in tissue composition between lesion and healthy tissue is considered, malignant lesions are characterized by significantly higher collagen content than benign lesions. Also the best model for the discrimination of malignant lesions obtained applying regression logistic to tissue composition is based only on collagen. Including demographic information into the model improves its specificity.

  4. A composite malignant tumour of the elderly female breast

    PubMed Central

    Wayte, D. M.; Stewart, J. B.; McKenzie, C. G.

    1970-01-01

    A composite malignant tumour arising in the breast of an elderly woman is described. The cystic tumour containing areas of squamous metaplasia, bone formation, adenocarcinoma, and osteosarcoma was surrounded by the typical changes of mammary dysplasia (fibroadenosis). The classification and acceptance of such tumours is highly debatable. There is no one acceptable classification of breast sarcomas and hence the prognosis of such neoplasms, particularly those containing heterologous tissues, is poorly defined. Evidence is presented in support of such composite tumours as being definite entities which arise from the closely associated epithelial and mesenchymal components of the breast simultaneously. Images PMID:4320045

  5. Analysis of human breast tissues with Raman microspectroscopy

    NASA Astrophysics Data System (ADS)

    Liu, Gang; Zhang, Lin; Liu, Jianhong; Yu, Fan; Sun, Shizhong

    2006-01-01

    Raman microspectroscopy was used to study normal, benign and malignant human breast tissues. The Raman spectrum of normal breast tissue recorded with 514.5 nm line of Ar + laser excitation contains features attributed to carotenoids and lipids. The CH II bending mode near 1447 cm -1 in normal tissue shifts up to 1454 cm -1 in diseased tissues (benign and malignant). The band near 1660 cm -1 in normal tissue is narrow and sharp; whereas the band is broaden in the diseased tissues. In the region of C-H stretching mode, the 2902-/2860-cm -1 intensity ratio shows differences among normal, benign and malignant breast tissues. The ratio is the smallest in carcinoma tissue. The observed spectra differences may be used to probe breast lesion. The results show that Raman spectroscopic technique may have clinical applications.

  6. Optically measured microvascular blood flow contrast of malignant breast tumors.

    PubMed

    Choe, Regine; Putt, Mary E; Carlile, Peter M; Durduran, Turgut; Giammarco, Joseph M; Busch, David R; Jung, Ki Won; Czerniecki, Brian J; Tchou, Julia; Feldman, Michael D; Mies, Carolyn; Rosen, Mark A; Schnall, Mitchell D; DeMichele, Angela; Yodh, Arjun G

    2014-01-01

    Microvascular blood flow contrast is an important hemodynamic and metabolic parameter with potential to enhance in vivo breast cancer detection and therapy monitoring. Here we report on non-invasive line-scan measurements of malignant breast tumors with a hand-held optical probe in the remission geometry. The probe employs diffuse correlation spectroscopy (DCS), a near-infrared optical method that quantifies deep tissue microvascular blood flow. Tumor-to-normal perfusion ratios are derived from thirty-two human subjects. Mean (95% confidence interval) tumor-to-normal ratio using surrounding normal tissue was 2.25 (1.92-2.63); tumor-to-normal ratio using normal tissues at the corresponding tumor location in the contralateral breast was 2.27 (1.94-2.66), and using normal tissue in the contralateral breast was 2.27 (1.90-2.70). Thus, the mean tumor-to-normal ratios were significantly different from unity irrespective of the normal tissue chosen, implying that tumors have significantly higher blood flow than normal tissues. Therefore, the study demonstrates existence of breast cancer contrast in blood flow measured by DCS. The new, optically accessible cancer contrast holds potential for cancer detection and therapy monitoring applications, and it is likely to be especially useful when combined with diffuse optical spectroscopy/tomography. PMID:24967878

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

    PubMed

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

    2016-09-01

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

  8. Retinoids, carotenoids, and tocopherols in breast adipose tissue and serum of benign breast disease and breast cancer patients

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Various retinoic acid (RA) isomers (all-trans, 13-cis, 11-cis, and 9-cis) as well as retinol, carotenoids, and tocopherol concentrations were determined in both serum and breast adipose tissue of 22 benign breast disease patients and 52 breast cancer patients categorized into 4 stages by malignancy....

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

    PubMed

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

    2016-06-01

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

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

    PubMed Central

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

    2016-01-01

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

  11. Breast ultrasound imaging phantom to mimic malign lesion characteristics

    NASA Astrophysics Data System (ADS)

    de Carvalho, I. M.; Basto, R. L. Q.; Infantosi, A. F. C.; von Krüger, M. A.; Pereira, W. C. A.

    2010-01-01

    Ultrasound (US) phantoms are used to simulate the main acoustic properties of human soft tissues and are usually applied in guided biopsy training and equipment calibration. In this work it is presented an ultrasound phantom that mimics breast lesions with irregular edge, which is a typical feature related to malignancy. The phantom matrix was made of a mixture of water, agar, glycerine and graphite and PVC powders and the lesions were of silicon and polyacrylamide. The mimicking properties were US attenuation, propagation speed and density. The images obtained were visually compatible to malignant and benign lesions and are meant to be used as references for evaluation of segmentation algorithms for image processing.

  12. Dermatofibrosarcoma Protuberans: A Rare Malignancy of the Breast

    PubMed Central

    Al-Rahbi, Salim; Al-Lawati, Taha; Al-Kharusi, Suad; Thomas, Sosamma; Al-Harrasi, Khoula

    2015-01-01

    Dermatofibrosarcoma protuberans (DFSP) of the breast is a rare skin cancer with only a few cases reported in the literature. It corresponds to approximately 1% of all soft tissue sarcomas and to less than 0.1% of all malignancies with annual incidence of 0.8–4.5 cases per million. DFSP usually affects young and middle-aged adults and it can affect any site, but most commonly the trunk and extremities. This tumor arises from the deep dermis and subcutaneous tissues and is usually locally aggressive, but rarely metastasizes. Surgery including wide local excision with free margins remains the main modality of treatment. We report a case in a 28-year-old Omani woman who presented with a right breast lump to a local secondary hospital. She was offered excision biopsy of the lump and the histology came as DFSP with involved margins. The patient was then referred to the Breast Unit at the Royal Hospital where she was reviewed by multidisciplinary team including breast surgeons, oncologists, radiation oncologists, pathologists, and breast radiologists. Her laboratory and radiological investigations did not show any signs of distal metastasis and breast ultrasound did not reveal any residual breast lesions. We performed a wide re-excision of the previous surgical scar with the underlying breast tissues down to the level of the pectoral fascia followed by treatment with radiotherapy. The final histology report showed the presence of a 4×5mm residual tumor, and all resection margins were tumor-free. At six months follow-up, she had no signs of local recurrence. We publish this case report because of its rarity. PMID:26421120

  13. The differentiation of malignant and benign human breast tissue at surgical margins and biopsy using x-ray interaction data and Bayesian classification

    NASA Astrophysics Data System (ADS)

    Mersov, A.; Mersov, G.; Al-Ebraheem, A.; Cornacchi, S.; Gohla, G.; Lovrics, P.; Farquharson, M. J.

    2014-02-01

    Worldwide, about 1.3 million women are diagnosed with breast cancer annually with an estimated 465,000 deaths. Accordingly, there is a need for high accuracy and speed in diagnosis of lesions suspected of being cancerous. This study assesses the interaction data collected from low energy x-rays within breast tissue samples. Trace element concentrations are assessed using x-ray fluorescence, as well as electron density, and molecular structure which are examined using incoherent and coherent scatter, respectively. Our work to date has shown that such data can provide a quantitative measure of certain tissue characterising parameters and hence, through appropriate modelling, could be used to classify samples for uses such as surgical margin detection and biopsy examination. The parameters used in this study for comparing the normal and tumour tissue sample populations are: levels of elements Ca, Cu, Fe, Br, Zn, Rb, K; the area, FWHM and amplitude from peaks fitted to the coherent scatter profile that are associated with fat, fibre and water content; the ratio of the Compton and coherent scatter peak area, FWHM and amplitude from the incoherent scatter profile. The novelty of the approach to this work lies in the fact that the classification process does not rely on one source of data but combines several measurements, the data from which in this application are modelled using a method based on Bayesian classification. The reliability of the classifications was assessed by its application to diagnostically known data that was not itself included in the thresholds determination. The results of the classification of over 70 breast tissue samples will be presented in this study. Bayesian modelling was carried out using selected significant parameters for classification resulting in 71% of normal tissue samples (n=35) and 66% of tumour tissue samples (n=35) being correctly classified when using all the samples. Bayesian classification using the same variables on all

  14. Malignant hyperechoic breast lesions at ultrasound: A pictorial essay.

    PubMed

    Tiang, Stephen; Metcalf, Cecily; Dissanayake, Deepthi; Wylie, Elizabeth

    2016-08-01

    Malignant breast lesions are typically hypoechoic at sonography. However, a small subgroup of hyperechoic malignant breast lesions is encountered in clinical practice. We present a pictorial essay of a number of different hyperechoic breast malignancies with mammographic, sonographic and histopathologic correlation. Suspicious sonographic features in a hyperechoic lesion include inhomogeneity in echogenic pattern, an irregular margin, posterior acoustic shadowing and internal vascularity. A hyperechoic lesion at ultrasound does not discount the need to undertake histological assessment of a mammographically suspicious lesion. PMID:27216965

  15. Giant malignant phyllodes tumour of breast.

    PubMed

    Krishnamoorthy, Ramakrishnan; Savasere, Thejas; Prabhuswamy, Vinod Kumar; Babu, Rajashekhara; Shivaswamy, Sadashivaiah

    2014-01-01

    The term phyllodes tumour includes lesions ranging from completely benign tumours to malignant sarcomas. Clinically phyllodes tumours are smooth, rounded, and usually painless multinodular lesions indistinguishable from fibroadenomas. Percentage of phyllodes tumour classified as malignant ranges from 23% to 50%. We report a case of second largest phyllodes tumour in a 35-year-old lady who presented with swelling of right breast since 6 months, initially small in size, that progressed gradually to present size. Examination revealed mass in the right breast measuring 36×32 cms with lobulated firm surface and weighing 10 kgs. Fine needle aspiration cytology was reported as borderline phyllodes; however core biopsy examination showed biphasic neoplasm with malignant stromal component. Simple mastectomy was done and specimen was sent for histopathological examination which confirmed the core biopsy report. Postoperatively the patient received chemotherapy and radiotherapy. The patient is on follow-up for a year and has not shown any evidence of metastasis or recurrence. PMID:25548696

  16. [Cancer in ectopic breast tissue].

    PubMed

    Røikjer, Johan; Lindmark, Ida; Knudsen, Thor

    2015-06-15

    Two different forms of ectopic breast tissue exist in human beings: supernumerary and aberrant. Both forms are usually seen alongside the milk lines, which extend from the upper limbs to the inguinal region where they give rise to mammary glands, areolas and nipples. Although ectopic- and orthotopic breast tissue are placed in different areas of the body, they still share the same ability to undergo pathological degeneration. The focus of this case report is to shed light on this unusual form of breast cancer, and raise the level of awareness in cases with lumps located in the milk lines. PMID:26101129

  17. Breast reconstruction - natural tissue

    MedlinePlus

    ... muscle flap; TRAM; Latissimus muscle flap with a breast implant; DIEP flap; DIEAP flap; Gluteal free flap; ... If you are having breast reconstruction at the same time as mastectomy, the surgeon may do either of the following: Skin-sparing mastectomy. This means ...

  18. Malignant eccrine poroma in breast cancer-related lymphoedema.

    PubMed

    Lynch, M D; Jones, A E; Marker, A; Grant, J W; Purushotham, A D

    2004-11-01

    We describe the first case of malignant eccrine poroma arising in a lymphoedematous site. The patient had long-standing lymphoedema of the upper limb following breast cancer treatment. Lymphoedema is a recognised complication of breast cancer treatment and a risk factor for the subsequent development of malignancy. Possible mechanisms for this are discussed. PMID:16749962

  19. Breast reconstruction - natural tissue

    MedlinePlus

    ... a breast implant; DIEP flap; DIEAP flap; Gluteal free flap; Transverse upper gracilis flap; TUG ... is medicine that keeps you asleep and pain-free. For TRAM surgery: The surgeon makes a cut ( ...

  20. Tumor-associated macrophages: unwitting accomplices in breast cancer malignancy

    PubMed Central

    Williams, Carly Bess; Yeh, Elizabeth S; Soloff, Adam C

    2016-01-01

    Deleterious inflammation is a primary feature of breast cancer. Accumulating evidence demonstrates that macrophages, the most abundant leukocyte population in mammary tumors, have a critical role at each stage of cancer progression. Such tumor-associated macrophages facilitate neoplastic transformation, tumor immune evasion and the subsequent metastatic cascade. Herein, we discuss the dynamic process whereby molecular and cellular features of the tumor microenvironment act to license tissue-repair mechanisms of macrophages, fostering angiogenesis, metastasis and the support of cancer stem cells. We illustrate how tumors induce, then exploit trophic macrophages to subvert innate and adaptive immune responses capable of destroying malignant cells. Finally, we discuss compelling evidence from murine models of cancer and early clinical trials in support of macrophage-targeted intervention strategies with the potential to dramatically reduce breast cancer morbidity and mortality. PMID:26998515

  1. Analysis of breast tissue calcifications using FTIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Baker, Rebecca N.; Rogers, Keith D.; Shepherd, Neil; Stone, Nicholas

    2007-07-01

    Microalcifications can be found in both benign and malignant breast lesions and their composition can indicate the disease state. Type I microcalcifications are composed of calcium oxalate dihydrate (COD) and are associated mainly with benign tissue, whereas hydroxyapatite (HAP) can be present in both tissue types. As current practices such as mammography and histopathology examine the morphology of the specimen, they can not reliably distinguish between the two types of calcification, which frequently are the only mammographic features that indicate the presence of a cancerous lesion. Analysis of tissue by Fourier transform infrared microspectroscopy (FTIR) allows biochemical information to be achieved from the sample. Spectral maps have been carried out on paraffinized sections of breast tissue from 9 patients of different pathology types containing calcification. The chemical composition of the calcifications and surrounding tissue has been analysed and correlated with tissue pathology. This preliminary study has demonstrated the ability to conduct FTIR in paraffinized sections of breast tissue, and initial observations show a correlation between HAP carbonate substitution and tissue pathology. It is hoped that this and further studies will give insight into how the calcifications are linked to the disease process and will give an increased understanding of the significance of calcifications in breast tissue. If type II microcalcifications can be differentiated in benign and malignant tissue by spectroscopic techniques, this may have positive implications in early diagnosis if the techniques can be applied in vivo and spectroscopy of paraffin sections enables biochemical information to accompany histopathology of the sample.

  2. Significance of nuclear morphometry in benign and malignant breast aspirates

    PubMed Central

    Narasimha, Aparna; Vasavi, B; Kumar, Harendra ML

    2013-01-01

    Background: Breast carcinoma is one of the most common cancers occurring in the female population world-wide. Normal cells gradually transform to form the cancer cells through several stages. Nuclear changes occurring during these transformational steps need to be assessed objectively. Hence nuclear morphometry can be used as a diagnostic tool. Aim: To compare the nuclear morphometric parameters of benign and malignant breast aspirates. Study Design: Cytology was used to categorize aspirates from the breast lumps in to malignant (30 cases), and benign (30 cases). Nuclear parameters were calculated using the Image J 1.44C morphometric software. Several nuclear size parameters were analyzed. Results: The nuclear area, perimeter, diameter, compactness, and concave points were found to be statistically significant (P < 0.05) parameters in differentiating benign, and malignant aspirates. Conclusion: Nuclear morphometry was thus, a useful objective tool in the differentiating benign, and malignant breast lesions. PMID:23776836

  3. Biomonitoring of organochlorines in women with benign and malignant breast disease

    SciTech Connect

    Siddiqui, M.K.J. . E-mail: mkjs@rediffmail.com; Anand, M.; Mehrotra, P.K.; Sarangi, R.; Mathur, N.

    2005-06-01

    Established risk factors for breast cancer explain breast cancer risk only partially. Organochlorines are considered to be a possible cause for hormone-dependent cancers. A hospital-based case-control study, the first from India, was conducted among 50 women undergoing surgery for breast disease to examine the association between organochlorine exposure and breast cancer risk. Blood, tumor, and surrounding adipose tissue of the breast were collected from the subjects with benign (control) and malignant breast (study) lesions and analyzed to determine organochlorine insecticides using a gas-liquid chromatograph equipped with an electron capture detector. The {alpha}, {beta}, {gamma}, and {delta} isomers of hexachlorocyclohexane (HCH), p,p'-dichlorodiphenyltrichloroethane (DDT), o,p'-DDT, p,p-dichlorodiphenyldichloroethylene, and p,p'-dichlorodiphenyldichloroethane were frequently detected in three specimens. Total HCH and total DDT levels were higher in the blood of the study group (25 cases) than in those of the controls (25 cases) with only {gamma}-HCH being significantly different (P0.05). However, both total HCH and total DDT were higher in the tumor tissues of the controls than in those of the study group; {gamma}-HCH was significantly different (P0.05). The level of total HCH ({alpha}-HCH was significantly different, P0.05) was higher in the breast adipose tissue of the study group, whereas total DDT was higher in the breast adipose tissue of the control group. The distribution of known confounders of breast cancer including age, body mass index, age at menarche and menopause, duration of breast feeding, and family history related to breast disease did not differ significantly between benign and malignant groups. This pilot study with limited statistical power does not support a positive association between exposure to organochlorines and risk of breast cancer but paves the way for a larger Indian study with greater statistical power encompassing different

  4. Expression of oestrogen receptor alpha variants in non-malignant breast and early invasive breast carcinomas.

    PubMed

    Chappell, S A; Johnson, S M; Shaw, J A; Walker, R A

    2000-10-01

    Oestrogen receptor (ER) alpha variants have been described in normal breast and breast carcinomas, but their presence in a range of benign conditions and in small early invasive breast carcinomas has not been considered. Cryostat tissue sections from 19 normal and proliferative breast lesions and 44 carcinomas 15 mm and less in size detected by mammographic screening were screened for ERalpha splice variants using reverse transcriptase-nested PCR. The carcinomas were assessed for mutation by single-stranded conformational polymorphism analysis and variant forms/band shifts were sequenced. ERalpha was detected in all 19 non-malignant cases and exon 7-deleted variants were found in 16 of them. Three cases showed weak expression of exon 5, and two of exon 3 variants. There was no relationship between the presence of variants and the extent of proliferative change, ER status or age. ERalpha mRNA was not detected in two carcinomas; exon 3 deletions were found in four (9. 5%) of the other carcinomas, exon 5 in two (4.8%), and exon 7 in 11 (26.2%), with two variants in four carcinomas and a total of 29.5% of all cases having detectable variants. Two point mutations were found in one, which was a tubular carcinoma. Variant forms were identified in carcinomas of all sizes (bar<10 mm) but were more frequent in those of 15 mm. There was no relationship with type, grade or receptor status. The main difference between non-malignant breast and early invasive cancers related to exons 3 and 5. The findings suggest that ERalpha variants are not involved in breast cancer development but occur with tumour progression and may be a consequence rather than a cause. PMID:11004691

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

    PubMed

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

    2014-06-01

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

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

    PubMed Central

    Scaling, Allison L.

    2014-01-01

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

  7. Multicellular architecture of malignant breast epithelia influences mechanics.

    PubMed

    Venugopalan, Gautham; Camarillo, David B; Webster, Kevin D; Reber, Clay D; Sethian, James A; Weaver, Valerie M; Fletcher, Daniel A; El-Samad, Hana; Rycroft, Chris H

    2014-01-01

    Cell-matrix and cell-cell mechanosensing are important in many cellular processes, particularly for epithelial cells. A crucial question, which remains unexplored, is how the mechanical microenvironment is altered as a result of changes to multicellular tissue structure during cancer progression. In this study, we investigated the influence of the multicellular tissue architecture on mechanical properties of the epithelial component of the mammary acinus. Using creep compression tests on multicellular breast epithelial structures, we found that pre-malignant acini with no lumen (MCF10AT) were significantly stiffer than normal hollow acini (MCF10A) by 60%. This difference depended on structural changes in the pre-malignant acini, as neither single cells nor normal multicellular acini tested before lumen formation exhibited these differences. To understand these differences, we simulated the deformation of the acini with different multicellular architectures and calculated their mechanical properties; our results suggest that lumen filling alone can explain the experimentally observed stiffness increase. We also simulated a single contracting cell in different multicellular architectures and found that lumen filling led to a 20% increase in the "perceived stiffness" of a single contracting cell independent of any changes to matrix mechanics. Our results suggest that lumen filling in carcinogenesis alters the mechanical microenvironment in multicellular epithelial structures, a phenotype that may cause downstream disruptions to mechanosensing. PMID:25111489

  8. Multicellular Architecture of Malignant Breast Epithelia Influences Mechanics

    PubMed Central

    Webster, Kevin D.; Reber, Clay D.; Sethian, James A.; Weaver, Valerie M.; Fletcher, Daniel A.; El-Samad, Hana; Rycroft, Chris H.

    2014-01-01

    Cell–matrix and cell–cell mechanosensing are important in many cellular processes, particularly for epithelial cells. A crucial question, which remains unexplored, is how the mechanical microenvironment is altered as a result of changes to multicellular tissue structure during cancer progression. In this study, we investigated the influence of the multicellular tissue architecture on mechanical properties of the epithelial component of the mammary acinus. Using creep compression tests on multicellular breast epithelial structures, we found that pre-malignant acini with no lumen (MCF10AT) were significantly stiffer than normal hollow acini (MCF10A) by 60%. This difference depended on structural changes in the pre-malignant acini, as neither single cells nor normal multicellular acini tested before lumen formation exhibited these differences. To understand these differences, we simulated the deformation of the acini with different multicellular architectures and calculated their mechanical properties; our results suggest that lumen filling alone can explain the experimentally observed stiffness increase. We also simulated a single contracting cell in different multicellular architectures and found that lumen filling led to a 20% increase in the “perceived stiffness” of a single contracting cell independent of any changes to matrix mechanics. Our results suggest that lumen filling in carcinogenesis alters the mechanical microenvironment in multicellular epithelial structures, a phenotype that may cause downstream disruptions to mechanosensing. PMID:25111489

  9. Elasto-Mammography: Elastic Property Reconstruction in Breast Tissues

    SciTech Connect

    Wang, Z. G.; Liu, Y.; Wang, G.; Sun, L. Z.

    2008-02-15

    Mammography is the primary method for screening and detecting breast cancers. However, it frequently fails to detect small tumors and is not quite specific in terms of tumor benignity and malignancy. The objective of this paper is to develop a new imaging modality called elasto-mammography that generates the modulus elastograms based on conventional mammographs. A new elastic reconstruction method is described based on elastography and mammography for breast tissues. Elastic distribution can be reconstructed through the measurement of displacement provided by mammographic projection. It is shown that the proposed elasto-mammography provides higher sensitivity and specificity than the conventional mammography on its own for breast cancer diagnosis.

  10. SOX10 expression in malignant melanoma, carcinoma, and normal tissues.

    PubMed

    Mohamed, Amr; Gonzalez, Raul S; Lawson, Diane; Wang, Jason; Cohen, Cynthia

    2013-12-01

    Sry-related HMg-Box gene 10 (SOX10) is a nuclear transcription factor that plays an important role in melanocytic cell differentiation. It has been shown to be a sensitive marker of melanoma including spindle and desmoplastic subtypes. We assessed its frequency of expression in melanoma, carcinoma, benign nevi, and non-neoplastic tissues with routine immunohistochemistry for SOX10. The 109 primary melanoma included 49 epithelioid, 19 spindle cell, 22 desmoplastic, and 19 mixed spindle cell/desmoplastic melanoma. All primary, except 8 desmoplastic melanoma, and 11 metastatic melanoma were strongly and diffusely nuclear SOX10-positive. Six desmoplastic melanoma had ≤10% cells positive, and 2 were <50% positive, all of 3+ intensity. Eighteen of 149 (12%) breast carcinoma were SOX10-positive. All 24 ovarian, 23 endometrial, 26 lung, and 25 colon carcinoma were SOX10-negative. All 43 benign nevi, 18 dysplastic nevi, 68 non-neoplastic and benign skins, and all 56 non-neoplastic breast tissue were SOX10-positive. The sensitivity and specificity for SOX10 in the diagnosis of melanoma are 1.0 and 0.93, respectively; the positive and negative predictive values are 0.87 and 1.0, respectively. SOX10 is a sensitive, specific marker for melanoma. As benign nevi also express SOX10, it cannot be used to differentiate between benign and malignant pigmented skin lesions. Only a small number of breast carcinoma (12%), and breast lobules, express SOX10; no carcinoma of the ovary, endometrium, lung, or colon expressed SOX10. PMID:23197006

  11. Fluorescence Spectroscopy of Human Nonmalignant and Malignant Cells and Tissues.

    NASA Astrophysics Data System (ADS)

    Glassman, Wenling Sha

    This thesis explores steady state and time resolved fluorescence spectroscopy from human malignant and non -malignant cells and tissues. The focus of these studies are the analysis of the excitation spectra, emission spectra, and decay time based on the contribution from several key intrinsic fluorophors: NAD(P)H, flavins, tryptophan, elastin and collagen that exist in different amounts in the human tissues and cells. The comparison between the spectra from malignant and non-malignant cells and tissues gives information on the changes that occur from non-malignancy to malignancy in the cells and tissues. The spectra of tissues and cells are also compared to help in understanding what fluorophors are responsible for fluorescence spectral differences between the malignant and non-malignant tissues and cells. The results in this thesis show that the spectral differences between the normal and cancerous tissues and cells exist in various wavelength ranges. The experimental data from GYN tissues have shown with over 95% of the sensitivity and specificity to separate malignant from non-malignant tissues using 300nm excitation. The 340nm band, which is mostly in response to intrinsic fluorophor (amino acid tryptophan), from malignant tissues were relatively higher then that from the non-malignant tissues. This might have been caused by the higher concentration of free tryptophan in the malignant tumor when compared to that of the normal tissue. This has been found in medical clinical study. The experimental data in this thesis also show that the fluorescence intensities around 450nm-460nm, which are mostly due to the intrinsic fluorophor coenzyme NADH, from both malignant cells in vitro and tissues in vitro are relatively higher than from non-malignant cells in vitro and tissues in vitro. These findings are reinforced by the faster decay time of the NADH fluorescence from normal cells in vitro than from neoplasm cells in vitro. Thus, the NADH in the mitochondria might be

  12. Differences in breast tissue oxygenation following radiotherapy.

    PubMed

    Dornfeld, Ken; Gessert, Charles E; Renier, Colleen M; McNaney, David D; Urias, Rodolfo E; Knowles, Denise M; Beauduy, Jean L; Widell, Sherry L; McDonald, Bonita L

    2011-08-01

    Tissue perfusion and oxygenation changes following radiotherapy may result from and/or contribute to the toxicity of treatment. Breast tissue oxygenation levels were determined in the treated and non-treated breast 1 year after radiotherapy for breast conserving treatment. Transcutaneous oxygenation varied between subjects in both treated and non-treated breast. Subjects without diabetes mellitus (n=16) had an average oxygenation level of 64.8 ± 19.9mmHg in the irradiated breast and an average of 72.3 ± 18.1mmHg (p=0.018) at the corresponding location in the control breast. Patients with diabetes (n=4) showed a different oxygenation pattern, with lower oxygenation levels in control tissue and no decrease in the irradiated breast. This study suggests oxygenation levels in normal tissues vary between patients and may respond differently after radiotherapy. PMID:21356563

  13. 31P magnetic resonance phospholipid profiles of neoplastic human breast tissues.

    PubMed Central

    Merchant, T. E.; Meneses, P.; Gierke, L. W.; Den Otter, W.; Glonek, T.

    1991-01-01

    Phospholipids from malignant, benign and noninvolved human breast tissues were extracted by chloroform-methanol (2:1) and analysed by 31P MR spectroscopy at 202.4 MHz. Thirteen phospholipids were identified as constituents of the profiles obtained among the 55 tissue specimens analysed. Observed patterns in phospholipid tissues profiles were distinct, allowing qualitative characterisation of the three tissue groups. Multivariate analysis of lysophosphatidylcholine (LPC) and an uncharacterised phospholipid were shown to be independently significant in predicting benign tissue histology as either fibrocystic disease or fibroadenoma in 92% of cases. Univariate analysis of relative mole-percentage of phosphorus concentrations of individual phospholipids using the Scheffé comparison procedure revealed that in malignant tissues, phosphatidylethanolamine was significantly elevated compared to benign (+ 32%) and noninvolved tissues (+ 22%). Phosphatidylinositol (+ 33%) and phosphatidylcholine plasmalogen (PC plas) (+ 25%) were increased in malignant compared to benign and LPC was decreased (-44%) in malignant compared to noninvolved. LPC was significantly depressed (-39%) in benign tissue compared to normal. Phospholipid indices computed to further characterise the three tissue groups showed PC plas/PC elevated in malignant tissue compared to benign and PE plas/PE depressed in malignant tissue compared to noninvolved. These findings support previous investigations reporting that the alkyl-phospholipid analogues of phosphatidylcholine are released by malignant tissues and that levels of ethanolamine are elevated in malignant tissues. Indices describing the choline-containing phospholipids showed that these lipids are depressed significantly in malignant tissue relative to healthy tissue. PMID:2039694

  14. Soy consumption and histopathologic markers in breast tissue using tissue microarrays.

    PubMed

    Maskarinec, Gertraud; Erber, Eva; Verheus, Martijn; Hernandez, Brenda Y; Killeen, Jeffrey; Cashin, Suzanne; Cline, J Mark

    2009-01-01

    This study examined the relation of soy intake with hormonal and proliferation markers in benign and malignant breast tissue using tissue microarrays (TMAs). TMAs with up to 4 malignant and 4 benign tissue samples for 268 breast cancer cases were constructed. Soy intake in early life and in adulthood was assessed by questionnaire. The TMAs were stained for estrogen receptor (ER) alpha, ERbeta, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2/neu), proliferating cell nuclear antigen (PCNA), and Ki-67 using standard immunohistochemical methods. Logistic regression was applied for statistical analysis. A higher percentage of women showed positive marker expression in malignant than in benign tissue. With one exception, HER2/neu, no significant associations between soy intake and pathologic markers were observed. Early life soy intake was associated with lower HER2/neu and PCNA staining of malignant tissue. In benign tissue, early life soy intake showed higher ER and PR expression, but no difference in proliferation markers. The results of this investigation provide some assurance that soy intake does not adversely affect markers of proliferation. TMAs were shown to be a useful tool for epidemiologic research. PMID:19838945

  15. The Thermal Activity of Normal and Malignant Tissues

    PubMed Central

    Cheng, Li-Yao

    1998-01-01

    The usefulness of metabolic heat measurements in quantifying the response of a solid tumour to anticancer treatment was evaluated. The heat production characteristic of malignant tissues, as measured from human stomach, breast and liver cancer samples, was observed to be inconsistent, and its value could be higher or lower than that of its normal tissue of origin. The various thermal activity responses of an experimental rat hepatoma to hepatic artery ligation, cryotherapy, intra-arterial (i.a) Adriamycin (2.4 mg/ kg), i.a. Norcantharidin (0.5 mg/kg) were next studied. The tumour/liver (T/L) ratio of untreated tumour-bearing rats was 0.83 but this fell to a minimum at 24 h in both the hepatic artery ligation and the cryosurgery groups. In these two groups marked fluctuations in the heat production of normal liver occurred with poor recovery of the T/ L ratio even at 2--3 weeks. In the Adriamycin group, the T/L ratio dropped to a minimum at 5 days, and in the Norcantharidin group, at 3 days. Minimal disturbances in the thermal activity of liver tissue occured in these two chemotherapy groups and the T/L ratio recovered by 3 weeks. Norcantharidin appeared as efficacious as Adriamycin in the treatment of hepatoma when evaluated in terms of thermal activity. PMID:9893237

  16. Targeting MCM2 function as a novel strategy for the treatment of highly malignant breast tumors

    PubMed Central

    Abe, Shinya; Yamamoto, Kouhei; Kurata, Morito; Abe-Suzuki, Shiho; Horii, Rie; Akiyama, Futoshi; Kitagawa, Masanobu

    2015-01-01

    Highly malignant tumors express high levels of the minichromosome maintenance 2 (MCM2) protein, which is associated with advanced tumor grade, advanced stage, and poor prognosis. In a previous study, we showed that Friend leukemia virus (FLV) envelope protein gp70 bound MCM2, impaired its nuclear translocation, and enhanced DNA-damage-induced apoptosis in FLV-infected hematopoietic cells when the cells expressed high levels of MCM2. Here, we show that MCM2 is highly expressed in clinical samples of invasive carcinoma of the breast, especially triple-negative breast cancer (TNBC), and in cancer stem cell (CSC) marker-positive breast cancer cells. To generate a cancer therapy model using gp70, we introduced the gp70 protein into the cytoplasm of murine breast cancer cells that express high levels of MCM2 by conjugating the protein transduction domain (PTD) of Hph-1 to gp70 (Hph- 1-gp70). Hph-1-gp70 was successfully transduced into the cytoplasm of breast cancer cells. The transduced protein enhanced the DNA damage-induced apoptosis of cancer cells in vitro and in vivo. Therefore, an MCM2-targeted strategy using Hph-1-gp70 treatment to induce DNA damage might be a successful therapy for highly malignant breast cancers such as TNBC and for the eradication of CSC-like cells from breast cancer tissue. PMID:26430873

  17. Primary breast adenocarcinoma in ectopic breast tissue in the vulva.

    PubMed

    McMaster, Jason; Dua, Anahita; Dowdy, Sean C

    2013-01-01

    Introduction. Accessory breast tissue is a rare finding in the general population with an incidence of 1-2%. An even rarer occurrence is accessory breast tissue afflicted with breast carcinoma. We present a brief report discussing diagnosis and management of a patient who presented with primary breast adenocarcinoma in vulval supranumerary tissue. Brief Report. A 60-year-old Caucasian female presented with a lesion in her left vulva that she first identified during adolescence. The lesion began to grow and ulcerate prompting her to receive treatment. Biopsy was inconclusive, and metastatic workup was negative, so her lesion was treated as an isolated breast lump and removed via wide local excision. Conclusion. Primary breast adenocarcinoma of the vulva is exceedingly rare. A paucity of the literature on this topic unfortunately means that strong evidence does not exist detailing the best management of this patient cohort. However, given that histological data confirms these cancers are virtually the same as breast cancers, it logically follows that the best treatment practices for breast cancer may be applied to treat these patients presenting with primary vulva cancers of ectopic breast tissue. PMID:24066246

  18. Infrared microspectroscopic imaging of benign breast tumor tissue sections

    NASA Astrophysics Data System (ADS)

    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.

  19. Time resolved optical biopsy spectroscopy of normal, benign and malignant tissues from NADH and FAD changes

    NASA Astrophysics Data System (ADS)

    Masilamani, V.; Das, B. B.; Secor, J.; AlSalhi, M.; Amer, S. B.; Farhat, K.; Rabah, D.; Alfano, R. R.

    2012-01-01

    Histo pathological examination is the gold standard to discriminate between benign and malignant growth of tissue. But this is invasive and stressful. Hence many non invasive imaging techniques, such as CT, MRI, PET, etc are employed, each having certain advantages and disadvantages. In this context optical biopsy is a newly emerging technique, since it employs non-ionizing radiation like light or laser, which could be shined directly or launched through optical fiber to reach any part of the body. This paper reports results of time resolved emission spectra of 24 excised tissue sample (normal control=12; benign=4; malignant=8) of breast and prostate, employing a 390nm, 100 fs, Ti-Sapphire laser pulses. The fluorescence decay times were measured using streak camera and fitted for single and bi- exponential decays with reliability of 97%. Our results show the distinct difference between normal, benign and malignant tissues attributed changes of NADH and FAD levels.

  20. Influence of nuclei segmentation on breast cancer malignancy classification

    NASA Astrophysics Data System (ADS)

    Jelen, Lukasz; Fevens, Thomas; Krzyzak, Adam

    2009-02-01

    Breast Cancer is one of the most deadly cancers affecting middle-aged women. Accurate diagnosis and prognosis are crucial to reduce the high death rate. Nowadays there are numerous diagnostic tools for breast cancer diagnosis. In this paper we discuss a role of nuclear segmentation from fine needle aspiration biopsy (FNA) slides and its influence on malignancy classification. Classification of malignancy plays a very important role during the diagnosis process of breast cancer. Out of all cancer diagnostic tools, FNA slides provide the most valuable information about the cancer malignancy grade which helps to choose an appropriate treatment. This process involves assessing numerous nuclear features and therefore precise segmentation of nuclei is very important. In this work we compare three powerful segmentation approaches and test their impact on the classification of breast cancer malignancy. The studied approaches involve level set segmentation, fuzzy c-means segmentation and textural segmentation based on co-occurrence matrix. Segmented nuclei were used to extract nuclear features for malignancy classification. For classification purposes four different classifiers were trained and tested with previously extracted features. The compared classifiers are Multilayer Perceptron (MLP), Self-Organizing Maps (SOM), Principal Component-based Neural Network (PCA) and Support Vector Machines (SVM). The presented results show that level set segmentation yields the best results over the three compared approaches and leads to a good feature extraction with a lowest average error rate of 6.51% over four different classifiers. The best performance was recorded for multilayer perceptron with an error rate of 3.07% using fuzzy c-means segmentation.

  1. Accessory breast tissue mimicking pedunculated lipoma.

    PubMed

    Husain, Musharraf; Khan, Sabina; Bhat, Ashraf; Hajini, Firdoos

    2014-01-01

    Accessory breast tissue is an uncommon condition which occurs in 0.4-6% of women. It is mostly located in the axilla where it can cause diagnostic difficulty, especially if it is unilateral and large. Usually it is bilateral and presents as an asymptomatic mass during pregnancy or lactation. The diagnosis of ectopic breast tissue is important as it can undergo the same pathological changes that occur in a normal breast, such as mastitis, fibrocystic disease and carcinoma. We present a case of a large right-sided accessory breast in a 32-year-old woman that was clinically diagnosed as pedunculated lipoma. However, subsequent histopathological examination proved it to be an accessory breast tissue with lactational changes. PMID:25006058

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

    NASA Astrophysics Data System (ADS)

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

    2005-08-01

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

  3. VOLUMETRIC LOCALISATION OF DENSE BREAST TISSUE USING BREAST TOMOSYNTHESIS DATA.

    PubMed

    Dustler, M; Petersson, H; Timberg, P

    2016-06-01

    This study attempted to use combined data from reconstructed digital breast tomosynthesis (DBT) volumes and density estimation of projection images to localise dense tissue inside the breast, using the assumption that the breast can be treated as consisting of only two types of tissue: fibroglandular (dense) and adipose (fatty). To be able to verify results, software breast phantoms generated using fractal Perlin noise were employed. Projection images were created using the PENELOPE Monte Carlo package. Dense tissue volume was estimated from the central projection image. The density image was used to determine the number of dense voxels at each pixel location, which were then placed using the DBT image as a template. The method proved capable of accurately determining the composition of 75±5 % of voxels. PMID:26922782

  4. Discrimination between benign and malignant lesions of the breast using ultrasound disparity mapping

    NASA Astrophysics Data System (ADS)

    Steinberg, Bernard D.; Carlson, Donald L.; Birnbaum, Julia A.

    2001-05-01

    A technique called disparity mapping (DM) processes pairs of ultrasound B-scan images collected while a sonographer varies the probe pressure slightly on the breast surface. Dm measures the apparent displacement of the tissue about each image point and subsequently constructs a correlation map which represents the similarity between the speckle patterns around each point. The continuity of the lesion perimeter in the correlation image is used to separate benign from malignant lesions, with high continuity corresponding well with benign lesions and highly segmented perimeters correlating with malignancies. Twenty five solid masses were evaluated, and the results were compared with histology from core or surgical biopsy, or with cytology from fine needle aspiration. The results analyzed all lesions correctly (15 cancers and 10 benign lesions). There were no false positives or false negatives. The results suggest that DM may be a useful tool in digitally diagnosing breast lesions and consequently in reducing the number of unnecessary biopsies.

  5. [History and care of malignant wounds in breast cancer].

    PubMed

    Fromantin, Isabelle; Alran, Séverine; Cassoux, Nathalie

    2013-11-01

    The first descriptions of ulcerated breast cancer date back to ancient Egypt. From the Greek and Roman periods to the Renaissance, fungating wounds were described, excised, cauterized and necrotized using various techniques and unguents. The foundations of some of the therapeutic strategies we still use today were developed.Today the management of inoperable malignant wounds that are not amenable to anti-cancer treatment remains complex and the symptoms are difficult to control. PMID:24409606

  6. Are Irregular Hypoechoic Breast Masses on Ultrasound Always Malignancies?: A Pictorial Essay

    PubMed Central

    Kim, Youe Ree; Kim, Hun Soo

    2015-01-01

    Irregular hypoechoic masses in the breast do not always indicate malignancies. Many benign breast diseases present with irregular hypoechoic masses that can mimic carcinoma on ultrasonography. Some of these diseases such as inflammation and trauma-related breast lesions could be suspected from a patient's symptoms and personal history. Careful ultrasonographic examination and biopsy could help to differentiate these from malignancies. PMID:26576116

  7. Coexistence of malignant phyllodes tumor and her2-positive locally advanced breast cancer in distinct breasts: A case report

    PubMed Central

    Sato, Tomoi; Muto, Ichiro; Sakai, Takeshi

    2016-01-01

    Introduction Phyllodes tumor of the breast is a rare biphasic neoplasm, accounting for less than 1% of all breast tumors. Coexistence of phyllodes tumor and breast cancer in distinct breasts is extremely rare. Case presentation A 47-year-old Japanese woman presented with bilateral breast lumps. A HER2-positive, unresectable invasive carcinoma in the right breast and fibroadenoma in the left were diagnosed via core needle biopsy. During chemotherapy with anti-HER2 therapy, the breast cancer shrank quickly, while the left breast lump suddenly enlarged. Under a diagnosis of malignant neoplasm of the breast, left mastectomy was performed. Malignant phyllodes tumor was diagnosed by postoperative histological examination and recurred in multiple areas as early as 2 months after surgery. Discussion Only 10 cases of coexisting phyllodes tumor and breast cancer in distinct breasts have been reported in the English literature. Phyllodes tumor associated with breast cancer in distinct breasts tends to be malignant. This is the first case of phyllodes tumor rapidly enlarging during anti-HER2 chemotherapy for locally advanced HER2-positive breast cancer. Conclusion Even during effective treatment of advanced or recurrent breast cancer, attention should also be paid to the contralateral breast for the possible association of a second malignancy such as phyllodes tumor. PMID:26773878

  8. Malignant Adenomyoepithelioma of the Breast and Responsiveness to Eribulin

    PubMed Central

    Lee, Suee; Oh, Sung Yong; Kim, Sung-Hyun; Lee, Ji Hyun; Kim, Dae Cheul; Cho, Se Heon; Lee, Miri

    2015-01-01

    Adenomyoepithelioma (AME) of the breast is an uncommon tumor characterized by its dual differentiation into luminal cells and myoepithelial cells. In most cases these tumors have a benign clinical course, but distant metastases have been reported. We present the case of a 51-year-old woman diagnosed with malignant AME. The patient underwent a right modified radical mastectomy, and pathological examination confirmed the diagnosis of malignant AME. Ten months after the operation, multiple hepatic, pleural, and abdominal wall metastases were detected. A number of palliative chemotherapeutic agents were tried, including anthracycline and taxanes. However, the disease continued to progress, and superior vena cava syndrome developed as a result of direct tumor invasion. The patient received salvage eribulin monotherapy. After two cycles of this treatment, her clinical symptoms were ameliorated, and a computed tomography scan showed a partial response. Eribulin chemotherapy was thus effective in treating malignant AME in this case. PMID:26770248

  9. Contralateral breast cancer and other second malignancies in patients treated by breast-conserving therapy with radiation

    SciTech Connect

    Kurtz, J.M.; Amalric, R.; Brandone, H.; Ayme, Y.; Spitalier, J.M.

    1988-08-01

    Metachronous contralateral breast cancers and other second malignancies were evaluated in 2,850 patients treated between 1960 and 1981 primarily with radiotherapy (RT) either alone or following breast-conserving surgery. One hundred eighty-four contralateral cancers were observed in 22,491 patient-years of observation (818 per 10(5) patient-years), with a cumulative probability of 4.5% at 5, 7.9% at 10, and 11% at 15 and 20 years. Compared to patients with unilateral tumors, those destined to develop contralateral cancers were younger (mean age 51.9 vs 56.6) and more often gave a family history of breast cancer. Contralateral breast cancers were more frequent for more extensive tumors (T3 10% vs T1-26%; with inflammatory signs 10.6% without 6%), and in patients with ipsilateral local recurrence (with 9.1%, without 5.6%). Patients with contralateral cancers had a significantly less favorable survival experience (15-year actuarial survival after primary therapy 42%) than patients without contralateral cancer (15-year survival 65.5%). In early stage patients treated with conservative surgery and RT, contralateral cancer was not prognostically more favorable than ipsilateral breast recurrence. Among 72 other second malignancies (320 per 10(5) patient-years) were 2 soft tissue sarcomas in the irradiated area. This corresponds to an incidence of 21 cases per 10(5) patient-years for survivors beyond the fifth year. The possible influence of RT on contralateral cancers and other second malignancies is discussed.

  10. Nonbreast Second Malignancies After Treatment of Primary Breast Cancer

    SciTech Connect

    Yadav, Budhi S. Sharma, Suresh C.; Patel, Firuza D.; Ghoshal, Sushmita; Kapoor, Rakesh; Kumar, Rajinder

    2009-04-01

    Purpose: To determine the incidence and risk factors for nonbreast second malignancies (NBSMs) in women after treatment for primary breast cancer. Methods and Materials: Between January 1985 and December 1995, a total of 1,084 breast cancer patients were analyzed for NBSMs. Detailed analysis was carried out for age, family history, disease stage, radiation therapy, chemotherapy, hormone therapy, other clinical/pathologic characteristics, and site of NBSMs. The Cox proportional hazard regression model was used to estimate the relative risk of NBSMs. Results: Median follow-up was 12 years. In total, 33 cases of NBSMs were noted in 29 patients. The overall incidence of NBSM was 3%, and the median time for NBSMs was 7 years. The most common NBSMs were gynecologic (22 patients), gastrointestinal (4 patients), head and neck (3 patients), hematologic (2 patients), lung (1 patient), and thyroid (1 patient). The NBSMs rate at 12 years was 2.4% for both mastectomy and radiation therapy groups. In the subset of patients less than 45 years of age at the time of treatment, the NBSMs rate was 0.7% as compared with 4.6% in patients more than 45 years of age (p = 0.001). Statistically significant higher incidences of endometrial and ovarian cancer were seen in patients with hormonal therapy (5.2%) as compared with patients without hormonal therapy (1.8%, p = 0.002). Women with a family history of breast cancer had a higher incidence (6%) of endometrial and ovarian malignancy compared with women without such a history (2.1%, p = 0.003). Chemotherapy did not affect the risk of second malignancy. Conclusion: The most common NBSMs in this study were gynecologic. Family history of breast cancer was a high risk factor for NBSMs. No risk of NBSMs with radiotherapy was observed.

  11. Mammaglobin 1 promotes breast cancer malignancy and confers sensitivity to anticancer drugs.

    PubMed

    Picot, Nadia; Guerrette, Roxann; Beauregard, Annie-Pier; Jean, Stéphanie; Michaud, Pascale; Harquail, Jason; Benzina, Sami; Robichaud, Gilles A

    2016-07-01

    Mammaglobin 1 (MGB1), a member of the secretoglobin family, is expressed in mammary epithelial tissues and is overexpressed in most mammary carcinomas. Despite the extensive research correlating MGB1 expression profiles to breast cancer pathogenesis and disease outcome, the biological significance of MGB1 in cancer processes is still unclear. We have thus set out to conduct a functional evaluation of the molecular and cellular roles of MGB1 in breast cancer processes leading to disease progression. Using a series of breast cancer cell models with conditional MGB1 expression, we demonstrate that MGB1 promotes cancer cell malignant features. More specifically, loss of MGB1 expression resulted in a decrease of cell proliferation, soft agar spheroid formation, migration, and invasion capacities of breast cancer cells. Concomitantly, we also observed that MGB1 expression activates signaling pathways mediated by MAPK members (p38, JNK, and ERK), the focal adhesion kinase (FAK), matrix metalloproteinases (MMPs) and NFκB. Moreover, MGB1 regulates epithelial to mesenchymal (EMT) features and modulates Snail, Twist and ZEB1 expression levels. Interestingly, we also observed that expression of MGB1 confers breast cancer cell sensitivity to anticancer drug-induced apoptosis. Together, our results support a role for MGB1 in tumor malignancy in exchange for chemosensitivity. These findings provide one of the first descriptive overview of the molecular and cellular roles of MGB1 in breast cancer processes and may offer new insight to the development of therapeutic and prognostic strategies in breast cancer patients. © 2015 Wiley Periodicals, Inc. PMID:26207726

  12. Adaptive Breast Radiation Therapy Using Modeling of Tissue Mechanics: A Breast Tissue Segmentation Study

    SciTech Connect

    Juneja, Prabhjot; Harris, Emma J.; Kirby, Anna M.; Evans, Philip M.

    2012-11-01

    Purpose: To validate and compare the accuracy of breast tissue segmentation methods applied to computed tomography (CT) scans used for radiation therapy planning and to study the effect of tissue distribution on the segmentation accuracy for the purpose of developing models for use in adaptive breast radiation therapy. Methods and Materials: Twenty-four patients receiving postlumpectomy radiation therapy for breast cancer underwent CT imaging in prone and supine positions. The whole-breast clinical target volume was outlined. Clinical target volumes were segmented into fibroglandular and fatty tissue using the following algorithms: physical density thresholding; interactive thresholding; fuzzy c-means with 3 classes (FCM3) and 4 classes (FCM4); and k-means. The segmentation algorithms were evaluated in 2 stages: first, an approach based on the assumption that the breast composition should be the same in both prone and supine position; and second, comparison of segmentation with tissue outlines from 3 experts using the Dice similarity coefficient (DSC). Breast datasets were grouped into nonsparse and sparse fibroglandular tissue distributions according to expert assessment and used to assess the accuracy of the segmentation methods and the agreement between experts. Results: Prone and supine breast composition analysis showed differences between the methods. Validation against expert outlines found significant differences (P<.001) between FCM3 and FCM4. Fuzzy c-means with 3 classes generated segmentation results (mean DSC = 0.70) closest to the experts' outlines. There was good agreement (mean DSC = 0.85) among experts for breast tissue outlining. Segmentation accuracy and expert agreement was significantly higher (P<.005) in the nonsparse group than in the sparse group. Conclusions: The FCM3 gave the most accurate segmentation of breast tissues on CT data and could therefore be used in adaptive radiation therapy-based on tissue modeling. Breast tissue segmentation

  13. Malignant soft tissue tumors in children.

    PubMed

    Thacker, Mihir M

    2013-10-01

    Soft tissue masses are frequently seen in children. Although most are benign or reactive, soft tissue sarcomas (STS)-both rhabdomyosarcoma (most common) and non-rhabdo STS, do occur in the extremities. Appropriate evaluation of extremity soft tissue tumors often includes a biopsy as the clinical and imaging features may not be enough to establish a definitive diagnosis. Much needs to be done for improving the treatment of these rare but often devastating sarcomas. Given the small numbers of these cases seen at various centers, collaborative efforts should be made to further our understanding and improve the management of these challenging cases. PMID:24095080

  14. Whole breast tissue characterization with ultrasound tomography

    NASA Astrophysics Data System (ADS)

    Duric, Neb; Littrup, Peter; Li, Cuiping; Roy, Olivier; Schmidt, Steve; Seamans, John; Wallen, Andrea; Bey-Knight, Lisa

    2015-03-01

    A number of clinical trials have shown that screening ultrasound, supplemental to mammography, detects additional cancers in women with dense breasts. However, labor intensity, operator dependence and high recall rates have limited adoption. This paper describes the use of ultrasound tomography for whole-breast tissue stiffness measurements as a first step toward addressing the issue of high recall rates. The validation of the technique using an anthropomorphic phantom is described. In-vivo applications are demonstrated on 13 breast masses, indicating that lesion stiffness correlates with lesion type as expected. Comparison of lesion stiffness measurements with standard elastography was available for 11 masses and showed a strong correlation between the 2 measures. It is concluded that ultrasound tomography can map out the 3 dimensional distribution of tissue stiffness over the whole breast. Such a capability is well suited for screening where additional characterization may improve the specificity of screening ultrasound, thereby lowering barriers to acceptance.

  15. FT-Raman spectroscopy study of human breast tissue

    NASA Astrophysics Data System (ADS)

    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.

  16. Fluorescence lifetime of normal, benign, and malignant thyroid tissues

    NASA Astrophysics Data System (ADS)

    Brandao, Mariana; Iwakura, Ricardo; Basilio, Fagne; Haleplian, Kaique; Ito, Amando; de Freitas, Luiz Carlos Conti; Bachmann, Luciano

    2015-06-01

    Fine-needle aspiration cytology is the standard technique to diagnose thyroid pathologies. However, this method results in a high percentage of inconclusive and false negatives. The use of time-resolved fluorescence techniques to detect biochemical composition and tissue structure alterations could help to develop a portable, minimally invasive, and nondestructive method to assist during surgical procedures. This study aimed to use fluorescence lifetimes to differentiate healthy and benign tissues from malignant thyroid tissue. The thyroid tissue was excited at 298-300 nm and the fluorescence decay registered at 340 and 450 nm. We observed fluorescence lifetimes at 340 nm emission of 0.80±0.26 and 3.94±0.47 ns for healthy tissue; 0.90±0.24 and 4.05±0.46 ns for benign lesions; and 1.21±0.14 and 4.63±0.25 ns for malignant lesions. For 450 nm emissions, we obtain lifetimes of 0.25±0.18 and 3.99±0.39 ns for healthy tissue, 0.24±0.17 and 4.20±0.48 ns for benign lesions, 0.33±0.32 and 4.55±0.55 ns for malignant lesions. Employing analysis of variance, we differentiate malignant lesions from benign and healthy tissues. In addition, we use quadratic discriminant analysis to distinguish malignant from benign and healthy tissues with an accuracy of 76.1%, sensitivity of 74.7%, and specificity of 83.3%. These results indicate that time-resolved fluorescence can assist medical evaluation of thyroid pathologies during surgeries.

  17. Autofluorescence of tissue surrounding malignant tumors

    NASA Astrophysics Data System (ADS)

    Lohmann, Wolfgang; Bohle, Rainer M.; Schill, Wolf-Bernhard; Vahrson, H.; Mussmann, J.

    1998-04-01

    In vitro fluorescence measurements on pap smears of ascites, pleura, or Douglas confirmed results obtained previously with different types of tissue: Cancer tissue fluoresces hardly and is surrounded by a 'fluorescence belt.' Investigations of cytological smears (e.g. Pap smears) have revealed the possible participation of granulocytes in this 'immune' reaction. Furthermore, there seems to be obvious differences in the fluorescence response of pap smears between ovarial- carcinomas and peritoneal carcinomas based on ovarial carcinoma. This observation cannot be explained yet. Because of its sensitivity and specificity the fluorescence method can be used as an additional tool for the evaluation of the tumor invasion front. Preferably it might be used for frozen sections of biopsies and surgical excisions.

  18. Grading Breast Cancer Tissues Using Molecular Portraits*

    PubMed Central

    Olsson, Niclas; Carlsson, Petter; James, Peter; Hansson, Karin; Waldemarson, Sofia; Malmström, Per; Fernö, Mårten; Ryden, Lisa; Wingren, Christer; Borrebaeck, Carl A. K.

    2013-01-01

    Tumor progression and prognosis in breast cancer patients are difficult to assess using current clinical and laboratory parameters, where a pathological grading is indicative of tumor aggressiveness. This grading is based on assessments of nuclear grade, tubule formation, and mitotic rate. We report here the first protein signatures associated with histological grades of breast cancer, determined using a novel affinity proteomics approach. We profiled 52 breast cancer tissue samples by combining nine antibodies and label-free LC-MS/MS, which generated detailed quantified proteomic maps representing 1,388 proteins. The results showed that we could define in-depth molecular portraits of histologically graded breast cancer tumors. Consequently, a 49-plex candidate tissue protein signature was defined that discriminated between histological grades 1, 2, and 3 of breast cancer tumors with high accuracy. Highly biologically relevant proteins were identified, and the differentially expressed proteins indicated further support for the current hypothesis regarding remodeling of the tumor microenvironment during tumor progression. The protein signature was corroborated using meta-analysis of transcriptional profiling data from an independent patient cohort. In addition, the potential for using the markers to estimate the likelihood of long-term metastasis-free survival was also indicated. Taken together, these molecular portraits could pave the way for improved classification and prognostication of breast cancer. PMID:23982162

  19. Optical imaging as an adjunct to sonograph in differentiating benign from malignant breast lesions

    NASA Astrophysics Data System (ADS)

    Zhu, Quing; Conant, Emily F.; Chance, Britton

    2000-04-01

    The role of near infrared (NIR) diffusive light imaging as an adjunct to ultrasound in differentiating benign from malignant lesions was evaluated in 27 mammography patients with infiltrating ductal carcinomas, apocrine metaplasia, fibroadenomas, radial scar and ductal hyperplasia, cysts, and normal tissues. Conventional ultrasound/mammography images were graded based on BI-RADS assessment categories. The spatial NIR measurements were made at wavelengths of 750 and 830 nm. Functional images, such as relative changes of deoxyhemoglobin (deoxyHb) and total blood concentration, were estimated from the dual wavelength measurements. Maximum relative deoxyHb and blood concentration changes were measured, and spatial correlation of masses in relative deoxyHb and blood concentration images for each breast were calculated. For the five biopsy proven benign lesions, ultrasound/mammography diagnoses were suspicious for malignancy (four cases) and highly suspicious for malignancy (one case). Four lesions showed less than 1.0 V maximum deoxyHb and less than 1.5 V maximum blood concentration levels on average and spatial image correlation showed no correlated masses in both deoxyHb and blood concentration images. For the four biopsy proven malignant lesions, ultrasound/mammography diagnoses were highly suspicious for malignancy. Maximum deoxyHb and blood concentration changes were greater than 2.9 V on average except one lesion which showed smaller deoxyHb signal (maximum 0.85 V) but the deoxyHb mass and blood concentration mass were highly correlated.

  20. Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression

    PubMed Central

    Mouw, Janna K; Yui, Yoshihiro; Damiano, Laura; Bainer, Russell O; Lakins, Johnathan N; Acerbi, Irene; Ou, Guanqing; Wijekoon, Amanda C; Levental, Kandice R; Gilbert, Penney M; Chen, Yunn-Yi; Weaver, Valerie M

    2014-01-01

    Tissue mechanics regulate development and homeostasis and are consistently modified in tumor progression. Nevertheless, the fundamental molecular mechanisms through which altered mechanics regulate tissue behavior and the clinical relevance of these changes remain unclear. We demonstrate that increased matrix stiffness modulates microRNA expression to drive tumor progression through integrin activation of β-catenin and MYC. Specifically, in human and mouse tissue, increased matrix stiffness induced miR-18a to reduce levels of the tumor suppressor PTEN, both directly and indirectly by decreasing levels of HOXA9. Clinically, extracellular matrix stiffness correlated significantly with miR-18a in human breast tumor biopsies. miR-18a expression was highest in basal-like breast cancers in which PTEN and HOXA9 levels were lowest and predicted for poor prognosis in patients with luminal breast cancers. Our findings identify a mechanically-regulated microRNA circuit that can promote malignancy and suggest potential prognostic roles for HOXA9 and miR-18a levels in stratifying patients with luminal breast cancers. PMID:24633304

  1. Determination of optical parameters of human breast tissue from spatially resolved fluorescence: a diffusion theory model

    NASA Astrophysics Data System (ADS)

    Nair, Maya S.; Ghosh, Nirmalya; Raju, Narisetti Sundar; Pradhan, Asima

    2002-07-01

    We report the measurement of optical transport parameters of pathologically characterized malignant tissues, normal tissues, and different types of benign tumors of the human breast in the visible wavelength region. A spatially resolved steady-state diffuse fluorescence reflectance technique was used to estimate the values for the reduced-scattering coefficient (mu's) and the absorption coefficient (mua) of human breast tissues at three wavelengths (530, 550, and 590 nm). Different breast tissues could be well differentiated from one another, and different benign tumors could also be distinguished by their measured transport parameters. A diffusion theory model was developed to describe fluorescence light energy distribution, especially its spatial variation in a turbid and multiply scattering medium such as human tissue. The validity of the model was checked with a Monte Carlo simulation and also with different tissue phantoms prepared with polystyrene microspheres as scatterers, riboflavin as fluorophores, and methylene blue as absorbers.

  2. Intrathymic primary intrathoracic goiter in a patient with breast malignancy.

    PubMed

    Barker, Thomas A; Daultrey, Charles R; Trotter, Simon E; Kalkat, Maninder

    2012-02-01

    We report a rare case of an intrathymic primary intrathoracic goiter. The patient with newly diagnosed breast carcinoma was also known to have a distinct large anterior mediastinal mass. This was removed via a median sternotomy, after a thorascopic biopsy had been performed in the past but a diagnosis had not been reached. A discussion relating to the extremely rare occurrence of intrathymic ectopic thyroid tissue and the surgical treatment of primary intrathoracic goiters is included. PMID:22269766

  3. Photoacoustic spectroscopic differences between normal and malignant thyroid tissues

    NASA Astrophysics Data System (ADS)

    Li, Li; Xie, Wengming; Li, Hui

    2012-12-01

    The thyroid is one of the main endocrine glands of human body, which plays a crucial role in the body's metabolism. Thyroid cancer mortality ranks only second to ovarian cancer in endocrine cancer. Routine diagnostic methods of thyroid diseases in present clinic exist misdiagnosis and missed diagnosis to varying degrees. Those lead to miss the best period of cancer treatment--early. Photoacoustic spectroscopy technology is a new tool, which provides an effective and noninvasive way for biomedical materials research, being highly sensitive and without sample pretreatment. In this paper, we use photoacoustic spectroscopy technology (PAST) to detect the absorption spectrum between normal and malignant thyroid tissues. The result shows that the photoacoustic spectroscopy technology (PAST) could differentiate malignant thyroid tissue from normal thyroid tissue very well. This technique combined with routine diagnostic methods has the potential to increase the diagnostic accuracy in clinical thyroid cancer diagnosis.

  4. VIS-NIR spectrum analysis for distinguishing tumor and normal human breast tissue

    NASA Astrophysics Data System (ADS)

    Zhang, Yang; Yu, Yuan; Tuchin, Valery V.; Chen, Yongjun; Wen, Xiang; Liu, Caihua; Wang, Jing; Xue, Xingbo; Zhu, Dan

    2012-03-01

    The high incidence and mortality of breast cancer require an effective method for early breast diagnosis. In order to investigate the optical differences among malignant tumor, benign tumor and normal human breast tissue, a commercial spectrophotometer combined with single integrating sphere was used to measure the optical properties of different types of breast tissue in the wavelength range of 400 nm to 2200 nm in vitro. The hematoxylin and eosin staining (H&E staining) are used as the standard, and to find the find possible optical markers from the corresponding absorption or scattering spectra. This work is not only used for in vitro rapid optical diagnosis, but very helpful to develop innovative optical diagnosis of breast tumor in vivo.

  5. Outcomes After Breast Conservation Treatment With Radiation in Women With Prior Nonbreast Malignancy and Subsequent Invasive Breast Carcinoma

    SciTech Connect

    Nemani, Deepika; Vapiwala, Neha Hwang, W.-T.; Solin, Lawrence J.

    2009-03-15

    Purpose: Little information has been reported regarding outcomes after treatment for patients with early-stage invasive breast cancer and a prior nonbreast malignancy. This report analyzes the outcomes in patients with Stage I and II breast cancer after breast conservation treatment (BCT) with a prior nonbreast malignancy. Methods and Materials: The study cohort comprised 66 women with invasive breast cancer and a prior nonbreast malignancy. All patients were treated with breast conservation surgery followed by definitive breast irradiation between 1978 and 2003. Median ages at diagnosis of invasive breast cancer and prior malignancy were 57 and 50 years, respectively. The median interval between the prior malignancy and breast cancer was 7.0 years. Median and mean follow-up times after BCT were 5.3 and 7.0 years. Results: The 5-year and 10-year overall survival rates were 94% (95% confidence interval [CI], 82-98%) and 78% (95% CI, 59-89%), respectively. There were 4 patients (6%) with local failure and 10 patients (15%) with distant metastases. The 10-year rate of local failure rate was 5% (95% CI, 2-16%) and freedom from distant metastases was 78% (95% CI, 61-88%). No obvious differences in survival or local control were noted compared with the reported results in the literature for patients with invasive breast cancer alone. Conclusions: Both overall survival and local control at 5 and 10 years were comparable to rates observed in early-stage breast cancer patients without a prior malignancy. Prior nonbreast malignancy is not a contraindication to BCT, if the primary cancer is effectively controlled.

  6. Generation of 3D synthetic breast tissue

    NASA Astrophysics Data System (ADS)

    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.

  7. COX7AR is a Stress-inducible Mitochondrial COX Subunit that Promotes Breast Cancer Malignancy.

    PubMed

    Zhang, Kezhong; Wang, Guohui; Zhang, Xuebao; Hüttemann, Philipp P; Qiu, Yining; Liu, Jenney; Mitchell, Allison; Lee, Icksoo; Zhang, Chao; Lee, Jin-Sook; Pecina, Petr; Wu, Guojun; Yang, Zeng-Quan; Hüttemann, Maik; Grossman, Lawrence I

    2016-01-01

    Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, plays a key role in regulating mitochondrial energy production and cell survival. COX subunit VIIa polypeptide 2-like protein (COX7AR) is a novel COX subunit that was recently found to be involved in mitochondrial supercomplex assembly and mitochondrial respiration activity. Here, we report that COX7AR is expressed in high energy-demanding tissues, such as brain, heart, liver, and aggressive forms of human breast cancer cells. Under cellular stress that stimulates energy metabolism, COX7AR is induced and incorporated into the mitochondrial COX complex. Functionally, COX7AR promotes cellular energy production in human mammary epithelial cells. Gain- and loss-of-function analysis demonstrates that COX7AR is required for human breast cancer cells to maintain higher rates of proliferation, clone formation, and invasion. In summary, our study revealed that COX7AR is a stress-inducible mitochondrial COX subunit that facilitates human breast cancer malignancy. These findings have important implications in the understanding and treatment of human breast cancer and the diseases associated with mitochondrial energy metabolism. PMID:27550821

  8. COX7AR is a Stress-inducible Mitochondrial COX Subunit that Promotes Breast Cancer Malignancy

    PubMed Central

    Zhang, Kezhong; Wang, Guohui; Zhang, Xuebao; Hüttemann, Philipp P.; Qiu, Yining; Liu, Jenney; Mitchell, Allison; Lee, Icksoo; Zhang, Chao; Lee, Jin-sook; Pecina, Petr; Wu, Guojun; Yang, Zeng-quan; Hüttemann, Maik; Grossman, Lawrence I.

    2016-01-01

    Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, plays a key role in regulating mitochondrial energy production and cell survival. COX subunit VIIa polypeptide 2-like protein (COX7AR) is a novel COX subunit that was recently found to be involved in mitochondrial supercomplex assembly and mitochondrial respiration activity. Here, we report that COX7AR is expressed in high energy-demanding tissues, such as brain, heart, liver, and aggressive forms of human breast cancer cells. Under cellular stress that stimulates energy metabolism, COX7AR is induced and incorporated into the mitochondrial COX complex. Functionally, COX7AR promotes cellular energy production in human mammary epithelial cells. Gain- and loss-of-function analysis demonstrates that COX7AR is required for human breast cancer cells to maintain higher rates of proliferation, clone formation, and invasion. In summary, our study revealed that COX7AR is a stress-inducible mitochondrial COX subunit that facilitates human breast cancer malignancy. These findings have important implications in the understanding and treatment of human breast cancer and the diseases associated with mitochondrial energy metabolism. PMID:27550821

  9. Male Breast: Clinical and Imaging Evaluations of Benign and Malignant Entities with Histologic Correlation.

    PubMed

    Chau, Alec; Jafarian, Neda; Rosa, Marilin

    2016-08-01

    Breast cancer is an uncommon disease in men. As a result, the diagnosis may not initially be considered. Understanding the common benign and malignant entities affecting the male breast is critical for timely and accurate diagnosis in the primary care setting. Most patients present with a palpable breast mass or pain. The usual etiology is gynecomastia, the most common breast condition in males, but breast cancer must always be excluded through careful imaging evaluation when physical examination findings are suspicious or inconclusive. Imaging of the male breast generally relies on mammography and ultrasound, with mammography employed as the initial imaging modality of choice and ultrasound when a mass is detected or suspected. Here we describe the normal male breast anatomy and present an evaluation algorithm for the male patient with breast signs or symptoms. The most common benign and malignant entities are described. PMID:26844632

  10. Breast adenomyoepithelioma and adenomyoepithelioma with carcinoma (malignant adenomyoepithelioma) with associated breast malignancies: A case series emphasizing histologic, radiologic, and clinical correlation.

    PubMed

    Moritz, August W; Wiedenhoefer, James F; Profit, Amanda P; Jagirdar, Jaishree

    2016-10-01

    The 2012 World Health Organization (WHO) classification of breast tumors distinguishes adenomyoepitheliomas (AMEs) as benign tumors composed of a biphasic proliferation of phenotypically variable myoepithelial cells around small epithelial lined spaces. Many AMEs have demonstrated benign behavior and are often cured with excision with negative margins, but some have exhibited malignant transformation of the myoepithelial cells, ductal epithelial cells, or both. When one of the components is histologically malignant, it is termed AME with carcinoma. Due to the rarity, the literature correlating imaging, histology, and clinical outcome is limited. A retrospective review was undertaken. A review of an institutional pathology database identified 14 cases with AME or malignant AME. Most AMEs had nonspecific imaging findings and were categorized as Bi-Rads 4. Histologic features of AME did not correlate with prior or concurrent breast malignancies or any radiographic features. Clinical follow up could be obtained for all but one case (mean follow up time = 75 months). 5 cases had no known treatment post-biopsy and 5 patients received mastectomy. No recurrences were noted. 3/13 cases of benign AME had associated breast malignancies including invasive ductal adenocarcinoma and ductal carcinoma in-situ. 1 case of malignant AME had a synchronous separate malignant phyllodes tumor. Given the unclear and unpredictable propensity for malignant transformation, conservative excision with negative margins currently seems appropriate. PMID:27494340

  11. Exploring Optical Contrast in Ex-Vivo Breast Tissue Using Diffuse Reflectance Spectroscopy and Tissue Morphology

    NASA Astrophysics Data System (ADS)

    Kennedy, Stephanie Ann

    In this research, ex-vivo breast tissue is evaluated to determine which sources of optical contrast have the potential to detect malignancy at the margins in women of differing breast composition. Then, H&E images of ex-vivo breast tissue sites are quantified to further deconstruct the relationship between optical scattering and the underlying tissue morphology. H&E images were taken of the malignant and benign sites and quantified to describe the % adipose, % collagen and % glands. Adipose sites, images at 10x, were predominantly fatty and quantified according to adipocyte morphology. H&E-stained adipose tissue sections were analyzed with an automated image processing algorithm to extract average cell area and cell density. Non-adipose sites were imaged with a 2.5x objective. Grids of 200µm boxes corresponding to the 3mm x 2mm area were overlaid on each non-adipose image. The non-adipose images were classified as the following: adipose and collagen (fibroadipose); collagen and glands (fibroglandular); adipose, collagen and glands (mixed); and malignant sites. Correlations between <μs‧> and % collagen in were determined in benign sites. Age, BMI, and MBD were then correlated to <μs‧> in the adipose and non-adipose sites. Variability in <μs‧> was determined to be related to collagen and not adipose content. In order to further investigate this relationship, the importance of age, BMI and MBD was analyzed after adjusting for the % collagen. Lastly, the relationship between % collagen and % glands was analyzed to determine the relative contributions of % collagen and % glands <μ s‧>. Statistics were calculated using Wilcoxon rank-sum tests, Pearson correlation coefficients and linear fits in R. Further deconstructing the relationship between optical scattering and tissue morphology resulted in a positive relationship between <μ s‧> and % collagen. Increased variability was observed in sites with a higher percentage of collagen. In adipose tissues MBD

  12. Malignant phylloides tumor of breast in a pregnant woman with coincidental nulliparous vaginal prolapse.

    PubMed

    Ray, Sabyasachi; Basak, Subhadeep; Das, Subhabrata; Pal, Mallika; Konar, Hiralal

    2011-12-01

    Malignant phylloides tumor is a relatively rare and rapidly growing tumor of the breast. Presentation during pregnancy is uncommon. Reports regarding malignancy in these tumors differ greatly in incidence, and most of them are stromal malignancies. We report this case in which 24-year old primigravid patient in the 36(th) week of her pregnancy had a malignant phylloides tumor of breast with sudden growth and fine needle aspiration cytology of the breast was positive for malignancy. Ultimately after her caesarean delivery, excision biopsy was in favor of a malignant process. Pregnancy with nulliparous prolapse is also a rare condition. Those conditions are not associated with each other, but presence of two rare conditions in the same time in the same person is unique. PMID:23115419

  13. Malignant Phylloides Tumor of Breast in a Pregnant Woman with Coincidental Nulliparous Vaginal Prolapse

    PubMed Central

    Ray, Sabyasachi; Basak, Subhadeep; Das, Subhabrata; Pal, Mallika; Konar, Hiralal

    2011-01-01

    Malignant phylloides tumor is a relatively rare and rapidly growing tumor of the breast. Presentation during pregnancy is uncommon. Reports regarding malignancy in these tumors differ greatly in incidence, and most of them are stromal malignancies. We report this case in which 24-year old primigravid patient in the 36th week of her pregnancy had a malignant phylloides tumor of breast with sudden growth and fine needle aspiration cytology of the breast was positive for malignancy. Ultimately after her caesarean delivery, excision biopsy was in favor of a malignant process. Pregnancy with nulliparous prolapse is also a rare condition. Those conditions are not associated with each other, but presence of two rare conditions in the same time in the same person is unique. PMID:23115419

  14. miR-4443 Participates in the Malignancy of Breast Cancer

    PubMed Central

    Chen, Xiu; Zhong, Shan-liang; Lu, Peng; Wang, Dan-dan; Zhou, Si-ying; Yang, Su-jin; Shen, Hong-yu; Zhang, Lei; Zhang, Xiao-hui; Zhao, Jian-hua; Tang, Jin-hai

    2016-01-01

    Purpose Chemo-resistance is the leading cause of failure in cancer therapy, however, much remains to be understood about the intrinsic mechanisms. In the present study, we discovered the novel miR-4443 that regulated malignancy of breast cancer both in vitro and in vivo. Methods We examined the expression of miR-4443 in MDA-MB-231/S and MDA-MB-231 Epirubicin-resistant cell lines with 76 breast cancer formalin-fixed paraffin-embedded tissues by real-time PCR. Also, we investigated the loss- and gain-functions of miR-4443 by MTT assay and flow cytometry. Furthermore, we detected miR-4443 mediated tissue inhibitor of metalloproteinase 2 expression in cells by TargetScan, RT-qPCR and western blot. Results We identified the up-regulated expression of miR-4443 in Epi-resistant cell lines versus MDA-MB-231/S cell(Epi versus S) and in post-chemotherapy FFPE tissues, along with statistically differential expressions in PR(partial response) versus SD(stable disease)/PD(progressive disease) patients. Overexpression of miR-4443 increased the IC50 value of Epi for the target cells transfected, while inhibition of miR-4443 could restored sensitivity of the target cells to Epi. Besides, down-regulation of endogenous miR-4443 by miRNA-inhibitors significantly enhanced Epi-induced apoptosis while up-regulation of miR-4443 by miRNA-mimics lead to less Epi-induced apoptotic cells. Consequently, changes in TIMP2 mRNA and protein expression revealed that miR-4443 mimics suppressed expression of TIMP2 and induced migration in breast cancer cells. Furthermore, TIMP2 expression associated with better prognosis(HR = 0.721, 95%CI: 0.529–0.983). Conclusions We revealed that miR-4443 induced malignancy of breast cancer mainly in chemo-resistance aspect for the very first time, providing a novel biomarker in breast cancer diagnosis and therapy. PMID:27504971

  15. Malignant lymphoma of the breast in a male patient: ultrasound imaging features.

    PubMed

    Ikeda, Tatsuhiko; Bando, Hiroko; Iguchi, Akiko; Tanaka, Yuko; Tohno, Eriko; Hara, Hisato

    2015-03-01

    Non-Hodgkin lymphoma (NHL) of the breast is a rare disease. Herein, we report a rare case of secondary involvement of the breast by NHL in a male patient and the ultrasound imaging findings. A 70-year-old man noticed an induration of the subareolar region of the right breast. He had been diagnosed as having mantle cell lymphoma 5 years before and treated with several series of chemoradiotherapy. On supine examination, palpation revealed bilateral breast enlargement, but detection of a lump was difficult. Ultrasonography showed a hypoechoic non-mass image-forming lesion in the subareolar region of the right breast. The final pathological diagnosis was recurrence of mantle cell lymphoma in the right breast. The diagnosis of malignant lymphoma of the breast by imaging modalities is difficult because there are no specific features. Breast lymphoma should be included with gynecomastia and breast cancer in the differential diagnosis of male patients with breast enlargement. PMID:22396322

  16. Using the laser-induced fluorescence spectroscopy in the differentiation between normal and neoplastichuman breast tissue.

    PubMed

    Hage, R; Galhanone, P R; Zângaro, R A; Rodrigues, K C; Pacheco, M T T; Martin, A A; Netto, M M; Soares, F A; da Cunha, I W

    2003-01-01

    This article reports results of the in vitro study for potential evaluation of the laser-induced fluorescence spectroscopy in the differentiation between normal and neoplastic human breast tissue. A coumarine dye laser pumped by nitrogen laser generated an excitation light centered at 458 nm. In order to collect the fluorescence signal was used an optical fiber catheter coupled to a spectrometer and CCD detector. Fluorescence spectra were recorded from normal and neoplastic (benign and malignant) human breast tissue, adding up 94 different areas. The discrimination between normal and neoplasm groups reach a sensitivity and specificity of 100%. PMID:14505202

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

    NASA Astrophysics Data System (ADS)

    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.

  18. Evidence That Breast Tissue Stiffness Is Associated with Risk of Breast Cancer

    PubMed Central

    Boyd, Norman F.; Li, Qing; Melnichouk, Olga; Huszti, Ella; Martin, Lisa J.; Gunasekara, Anoma; Mawdsley, Gord; Yaffe, Martin J.; Minkin, Salomon

    2014-01-01

    Background Evidence from animal models shows that tissue stiffness increases the invasion and progression of cancers, including mammary cancer. We here use measurements of the volume and the projected area of the compressed breast during mammography to derive estimates of breast tissue stiffness and examine the relationship of stiffness to risk of breast cancer. Methods Mammograms were used to measure the volume and projected areas of total and radiologically dense breast tissue in the unaffected breasts of 362 women with newly diagnosed breast cancer (cases) and 656 women of the same age who did not have breast cancer (controls). Measures of breast tissue volume and the projected area of the compressed breast during mammography were used to calculate the deformation of the breast during compression and, with the recorded compression force, to estimate the stiffness of breast tissue. Stiffness was compared in cases and controls, and associations with breast cancer risk examined after adjustment for other risk factors. Results After adjustment for percent mammographic density by area measurements, and other risk factors, our estimate of breast tissue stiffness was significantly associated with breast cancer (odds ratio = 1.21, 95% confidence interval = 1.03, 1.43, p = 0.02) and improved breast cancer risk prediction in models with percent mammographic density, by both area and volume measurements. Conclusion An estimate of breast tissue stiffness was associated with breast cancer risk and improved risk prediction based on mammographic measures and other risk factors. Stiffness may provide an additional mechanism by which breast tissue composition is associated with risk of breast cancer and merits examination using more direct methods of measurement. PMID:25010427

  19. The efficacy of Stokes Shift Spectroscopy for detecting prostate and breast cancer tissues

    NASA Astrophysics Data System (ADS)

    Pu, Yang; Wang, W. B.; Yang, Yuanlong; Alfano, Robert R.

    2013-03-01

    Stokes Shift Spectroscopy (S3) offers a novel way to rapidly measure spectral fingerprints of complex molecular mixtures in tissue. The changes of key fluorophores from normal state to the malignant state can be reflected by alteration of Stokes Shift Spectra (S3 spectra). S3 measurements can be used to acquire enough information of different key fluorophores from one spectrum to speed up spectral acquisition time. In this study, we demonstrate the usefulness of the S3 technique to distinguish the malignant tissue from the normal prostate and breast tissues. The optimal wavelength shift constant (Δλc) of S3 spectra measurements for prostate/breast cancer detection were determined to be 40 nm. The underlying physical and biological basis for S3 is discussed. For the first time, our work explicitly discloses how and why S3 is supreme in comparison with other conventional spectroscopic techniques.

  20. Image cytometry of duct cells from benign and malignant breast disease

    SciTech Connect

    Mayall, B.H.; Gadenne, C.; King, E.B.; Chew, K.L.; Duarte, L.A.; Petrakis, N.L.

    1987-01-22

    We used image cytometry to classify benign and malignant breast lesions, to identify parameters that classify premalignant lesions, and to assess these parameters for a biological association that may be linked with malignancy. Results suggest that quantitative image analysis is able to discriminate ''normal'' from ''abnormal'' breast lesions. Thus image cytometry may provide an objective approach for early detection of malignant changes in the breast. The parameters selected by stepwise discriminant and regression analyses as being most useful for discriminating among breast lesions relate to nuclear size, shape and DNA content. These parameters are robust and easily measured and are similar to those used by others for discriminating benign from malignant lesions. Significantly, no parameter based on nuclear chromatin distribution ranked as highly in this study, unlike our experience with studies of other premalignant lesions. 9 refs., 1 fig., 3 tabs.

  1. Comparison of microscopic vascularity in benign and malignant prostate tissue.

    PubMed

    Bigler, S A; Deering, R E; Brawer, M K

    1993-02-01

    A variety of malignant neoplasms have been shown to induce capillary neovascularization, and in some cases the degree of vascularization appears to correlate with aggressive behavior and risk of metastasis. We hypothesized that carcinoma of the prostate also induces the formation of new capillaries, and we developed a method to quantify the relative density of microscopic vessels in carcinoma of the prostate compared with benign prostatic glandular tissue. The number of microvessel profiles in tissue sections was quantified by marking the vascular endothelial cells with antibodies to factor VIII-related antigen using standard immunohistochemistry techniques and comparing fields of adenocarcinoma with benign glandular tissue in 15 radical prostatectomy specimens. The analysis was facilitated by using the Optimas computerized image analysis system (Bioscan, Seattle, WA) with software written for this investigation. Fourteen of the 15 cases demonstrated significantly higher vascular density in the areas of carcinoma than in the benign tissues. Overall, the ratio of vessels per unit area in sections of carcinoma versus benign tissue was approximately double (ratio = 2.02; P < .001). In benign tissues the capillaries are restricted for the most part to the periglandular stroma immediately adjacent to the epithelium, whereas the distribution in carcinoma appears to be more random. The data demonstrate the increased density of capillaries in prostatic carcinoma when compared with benign prostate tissue. PMID:8432518

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

    SciTech Connect

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

    2003-10-20

    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.

  3. Fluorescence spectra of benign and malignant prostate tissues

    NASA Astrophysics Data System (ADS)

    AlSalhi, M. S.; Masilamani, V.; Atif, M.; Farhat, K.; Rabah, D.; Turki, M. R. Al

    2012-09-01

    In this study, fluorescence emission spectrum (FES), Stokes' shift spectrum (SSS), and reflectance spectrum (RS) of benign (N = 12) and malignant prostate tissues (N = 8) were investigated to discriminate the two types of tissues. The FES was done with the excitation at 325 nm only; SSS with Δλ = 70 and Δλ = 0, the latter being equivalent to reflectance spectra. Of the three modes of spectra, SSS with Δλ = 70 nm showed the best discrimination. There were four important bands, one at 280 nm (due to tryptophan); 320 nm (due to elastin & tryptophan); 355 and 385 (due to NADH) and 440 nm (due to flavin). From the relative intensities of these bands, three ratios were evaluated. Similarly another two ratios were obtained from reflectance spectra and one more from FES. Thus, there are 6 ratio parameters which represent the relative concentration of tryptophan, elastin, nicotinamide adenine dinucleotide (NADH), and flavin. A statistical analysis showed that benign and malignant tissues could be classified with accuracy greater than 90%. This report is only for in vitro analysis; but employing optical fiber, this can be extended to in vivo analysis too, so that benign tumor could be distinguished without surgery.

  4. Predicting the Risk of Secondary Lung Malignancies Associated With Whole-Breast Radiation Therapy

    SciTech Connect

    Ng, John; Shuryak, Igor; Xu Yanguang; Clifford Chao, K.S.; Brenner, David J.; Burri, Ryan J.

    2012-07-15

    Purpose: The risk of secondary lung malignancy (SLM) is a significant concern for women treated with whole-breast radiation therapy after breast-conserving surgery for early-stage breast cancer. In this study, a biologically based secondary malignancy model was used to quantify the risk of secondary lung malignancies (SLMs) associated with several common methods of delivering whole-breast radiation therapy (RT). Methods and Materials: Both supine and prone computed tomography simulations of 15 women with early breast cancer were used to generate standard fractionated and hypofractionated whole-breast RT treatment plans for each patient. Dose-volume histograms (DVHs) of the ipsilateral breast and lung were calculated for each patient on each plan. A model of spontaneous and radiation-induced carcinogenesis was used to determine the relative risks of SLMs for the different treatment techniques. Results: A higher risk of SLMs was predicted for supine breast irradiation when compared with prone breast irradiation for both the standard fractionation and hypofractionation schedules (relative risk [RR] = 2.59, 95% confidence interval (CI) = 2.30-2.88, and RR = 2.68, 95% CI = 2.39-2.98, respectively). No difference in risk of SLMs was noted between standard fractionation and hypofractionation schedules in either the supine position (RR = 1.05, 95% CI = 0.97-1.14) or the prone position (RR = 1.01, 95% CI = 0.88-1.15). Conclusions: Compared with supine whole-breast irradiation, prone breast irradiation is associated with a significantly lower predicted risk of secondary lung malignancy. In this modeling study, fractionation schedule did not have an impact on the risk of SLMs in women treated with whole-breast RT for early breast cancer.

  5. Model predictions for the WAXS signals of healthy and malignant breast duct biopsies

    NASA Astrophysics Data System (ADS)

    LeClair, R. J.

    2014-03-01

    A wide-angle x-ray scatter (WAXS) measurement could potentially be used to determine whether a biopsy of a breast duct is healthy or malignant. A ductal carcinoma in situ (DCIS) occurs when the epithelial cells lining the wall start to replicate and invade the duct interior. Since cells are composed mainly of water a WAXS signal of DCIS could contain a larger component due to water. A model approximates that a breast duct biopsy consists of connective tissue (c.t.) and cells. For a 2 mm diameter 3.81 mm thick healthy duct biopsy, the volumes in cubic mm are 11.56 c.t. and 0.41 cells whereas 6.64 c.t. and 5.33 cells for DCIS. The differential linear scattering coefficients (μs) for both types of biopsies were calculated using the sum vc.t.μsc.t. + vcellμscell where v denotes fractional volume. The cell was assumed to be composed of water, lipids (fat), and other atoms associated with RNA, DNA, proteins, and carbohydrates. The μscell was calculated using the sum 0.771μswater + 0.023μsfat + 0.206μsother. The μs of c.t., water, and fat were available from literature whereas the independent atomic model approximation was used to calculate values for μsother. A WAXS model provided predictions of the number of 6 degree scattered photons Ns for incident 50 kV beams on healthy and malignant ducts. The sum of Ns between 31.5 <= E <= 45 keV were 1402 and 1529 for respectively the healthy and malignant biopsies. Using Poisson statistics, two Gaussian distributions, and a descision threshold set at their intersection, the false positive and false negative probabilities were 4.7% and 5.0%. This work suggests that DCIS could potentially be diagnosed via energy dispersive WAXS measurements.

  6. Immunohistological distribution of 5T4 antigen in normal and malignant tissues.

    PubMed

    Southall, P J; Boxer, G M; Bagshawe, K D; Hole, N; Bromley, M; Stern, P L

    1990-01-01

    A trophoblast cell surface antigen has been characterised by a monoclonal antibody (mAb) 5T4, raised following immunisation with solubilised wheat germ agglutinin binding glycoproteins from human syncytiotrophoblast plasma membrane (StMPM). The expression of the 72 kDa glycoprotein was assessed on cryostat sections of a range of neoplastic and non-neoplastic tissues, using an avidin-biotin immunoperoxidase technique. In products of conception, intense reactions were noted with villous syncytiotrophoblast membrane in normal early and term placenta, with weaker positivity of placental site trophoblast. Most normal or non-neoplastic tissues were negative, including liver, kidney, spleen, small intestine, ovary and testis. Faint or moderate positive reactions were present in some specialised epithelia. Of 115 neoplasms examined, 76 showed reactions with tumour cells including carcinomas of the bladder, breast, cervix, endometrium, lung, oesophagus, ovary, pancreas, stomach and testicular non-seminomatous germ cell tumours. Choriocarcinomas and placental site trophoblastic tumours were also positive. Most adenocarcinomas of colon and seminomas were negative as were all malignant melanomas and malignant lymphomas. A radioimmunoassay did not detect the antigen in either normal or pregnancy serum. The relatively low level of expression in normal tissues and reactivity with a wide range of carcinomas suggested that the antibody may be useful in diagnostic or targeting studies. PMID:2404511

  7. Soft tissue malignant lymphoma at sites of previous surgery.

    PubMed Central

    Radhi, J M; Ibrahiem, K; al-Tweigeri, T

    1998-01-01

    Three diffuse centroblastic lymphomas developed at the site of previous surgery. Two were preceded by atypical lymphoid infiltrates. Clinical data, microscopic features, and immunophenotypic studies were reviewed. All three patients presented with soft tissue masses at the site of previous surgery and metallic implants, with no evidence of lymphadenopathy, hepatosplenomegaly, or bone marrow involvement. There was no history of immunosuppression or risk factors. In two cases the initial diagnosis was of atypical lymphoid infiltrate progressing to lymphoma. Pathological examination showed a diffuse centroblastic lymphoma with an angiocentric pattern in one case. Phenotypic studies confirmed B cell origin. Soft tissue malignant lymphoma, though uncommon, can occur at the site of previous orthopaedic surgery, in particular joint replacement. Atypical lymphoid infiltrate may signal such an event. Images PMID:9828826

  8. Using Data Fusion to Characterize Breast Tissue

    SciTech Connect

    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. Time domain diffuse optical spectroscopy: In vivo quantification of collagen in breast tissue

    NASA Astrophysics Data System (ADS)

    Taroni, Paola; Pifferi, Antonio; Quarto, Giovanna; Farina, Andrea; Ieva, Francesca; Paganoni, Anna Maria; Abbate, Francesca; Cassano, Enrico; Cubeddu, Rinaldo

    2015-05-01

    Time-resolved diffuse optical spectroscopy provides non-invasively the optical characterization of highly diffusive media, such as biological tissues. Light pulses are injected into the tissue and the effects of light propagation on re-emitted pulses are interpreted with the diffusion theory to assess simultaneously tissue absorption and reduced scattering coefficients. Performing spectral measurements, information on tissue composition and structure is derived applying the Beer law to the measured absorption and an empiric approximation to Mie theory to the reduced scattering. The absorption properties of collagen powder were preliminarily measured in the range of 600-1100 nm using a laboratory set-up for broadband time-resolved diffuse optical spectroscopy. Optical projection images were subsequently acquired in compressed breast geometry on 218 subjects, either healthy or bearing breast lesions, using a portable instrument for optical mammography that operates at 7 wavelengths selected in the range 635-1060 nm. For all subjects, tissue composition was estimated in terms of oxy- and deoxy-hemoglobin, water, lipids, and collagen. Information on tissue microscopic structure was also derived. Good correlation was obtained between mammographic breast density (a strong risk factor for breast cancer) and an optical index based on collagen content and scattering power (that accounts mostly for tissue collagen). Logistic regression applied to all optically derived parameters showed that subjects at high risk for developing breast cancer for their high breast density can effectively be identified based on collagen content and scattering parameters. Tissue composition assessed in breast lesions with a perturbative approach indicated that collagen and hemoglobin content are significantly higher in malignant lesions than in benign ones.

  10. Alterations in replication timing of cancer-related genes in malignant human breast cancer cells.

    PubMed

    Fritz, Andrew; Sinha, Seema; Marella, Narasimharao; Berezney, Ronald

    2013-05-01

    The replication timing of nine genes commonly involved in cancer was investigated in the MCF10 cell lines for human breast cancer progression. Six of these nine genes are part of a constellation of tumor suppressor genes that play a major role in familial human breast cancer (TP53, ATM, PTEN, CHK2, BRCA1, and BRCA2). Three other genes are involved in a large number of human cancers including breast as either tumor suppressors (RB1 and RAD51) or as an oncogene (cMYC). Five of these nine genes (TP53, RAD51, ATM, PTEN, and cMYC) show significant differences (P < 0.05) in replication timing between MCF10A normal human breast cells and the corresponding malignant MCF10CA1a cells. These differences are specific to the malignant state of the MCF10CA1a cells since there were no significant differences in the replication timing of these genes between normal MCF10A cells and the non-malignant cancer MCF10AT1 cells. Microarray analysis further demonstrated that three of these five genes (TP53, RAD51, and cMYC) showed significant changes in gene expression (≥2-fold) between normal and malignant cells. Our findings demonstrate an alteration in the replication timing of a small subset of cancer-related genes in malignant breast cancer cells. These alterations partially correlate with the major transcriptional changes characteristic of the malignant state in these cells. PMID:23161755

  11. Increased PADI4 expression in blood and tissues of patients with malignant tumors

    PubMed Central

    2009-01-01

    Background Peptidylarginine deiminase type 4 (PAD4/PADI4) post-translationally converts peptidylarginine to citrulline. Recent studies suggest that PADI4 represses expression of p53-regulated genes via citrullination of histones at gene promoters. Methods Expression of PADI4 was investigated in various tumors and non-tumor tissues (n = 1673) as well as in A549, SKOV3 and U937 tumor cell lines by immunohistochemistry, real-time PCR, and western blot. Levels of PADI4 and citrullinated antithrombin (cAT) were investigated in the blood of patients with various tumors by ELISA (n = 1121). Results Immunohistochemistry detected significant PADI4 expression in various malignancies including breast carcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cancer cells, colorectal adenocarcinomas, renal cancer cells, ovarian adenocarcinomas, endometrial carcinomas, uterine adenocarcinomas, bladder carcinomas, chondromas, as well as other metastatic carcinomas. However, PADI4 expression was not observed in benign leiomyomas of stomach, uterine myomas, endometrial hyperplasias, cervical polyps, teratomas, hydatidiform moles, trophoblastic cell hyperplasias, hyroid adenomas, hemangiomas, lymph hyperplasias, schwannomas, neurofibromas, lipomas, and cavernous hemangiomas of the liver. Additionally, PADI4 expression was not detected in non-tumor tissues including cholecystitis, cervicitis and synovitis of osteoarthritis, except in certain acutely inflamed tissues such as in gastritis and appendicitis. Quantitative PCR and western blot analysis showed higher PADI4 expression in gastric adenocarcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cell cancers and breast cancers (n = 5 for each disease) than in the surrounding healthy tissues. Furthermore, western blot analysis detected PADI4 expression in cultured tumor cell lines. ELISA detected increased PADI4 and cAT levels in the blood of patients with various malignant tumors

  12. Adipose-Derived Stromal Vascular Fraction Differentially Expands Breast Progenitors in Tissue Adjacent to Tumors Compared to Healthy Breast Tissue

    PubMed Central

    Chatterjee, Sumanta; Laliberte, Mike; Blelloch, Sarah; Ratanshi, Imran; Safneck, Janice; Buchel, Ed

    2015-01-01

    Background: Autologous fat grafts supplemented with adipose-derived stromal vascular fraction are used in reconstructive and cosmetic breast procedures. Stromal vascular fraction contains adipose-derived stem cells that are thought to encourage wound healing, tissue regeneration, and graft retention. Although use of stromal vascular fraction has provided exciting perspectives for aesthetic procedures, no studies have yet been conducted to determine whether its cells contribute to breast tissue regeneration. The authors examined the effect of these cells on the expansion of human breast epithelial progenitors. Methods: From patients undergoing reconstructive breast surgery following mastectomies, abdominal fat, matching tissue adjacent to breast tumors, and the contralateral non–tumor-containing breast tissue were obtained. Ex vivo co-cultures using breast epithelial cells and the stromal vascular fraction cells were used to study the expansion potential of breast progenitors. Breast reduction samples were collected as a source of healthy breast cells. Results: The authors observed that progenitors present in healthy breast tissue or contralateral non–tumor-containing breast tissue showed significant and robust expansion in the presence of stromal vascular fraction (5.2- and 4.8-fold, respectively). Whereas the healthy progenitors expanded up to 3-fold without the stromal vascular fraction cells, the expansion of tissue adjacent to breast tumor progenitors required the presence of stromal vascular fraction cells, leading to a 7-fold expansion, which was significantly higher than the expansion of healthy progenitors with stromal vascular fraction. Conclusions: The use of stromal vascular fraction might be more beneficial to reconstructive operations following mastectomies compared with cosmetic corrections of the healthy breast. Future studies are required to examine the potential risk factors associated with its use. CLINICAL QUESTION/LEVEL OF EVIDENCE

  13. Value of Apparent Diffusion Coefficient Values in Differentiating Malignant and Benign Breast Lesions

    PubMed Central

    Bozkurt Bostan, Tuğba; Koç, Gonca; Sezgin, Gülten; Altay, Canan; Fazıl Gelal, M.; Oyar, Orhan

    2016-01-01

    Background: Magnetic resonance imaging (MRI) has become a diagnostic and problem solving method for the breast examinations in addition to conventional breast examination methods. Diffusion-weighted imaging (DWI) adds valuable information to conventional MRI. Aims: Our aim was to show the impact of apparent diffusion coefficient (ADC) values acquired with DWI to differentiate benign and malignant breast lesions. Study Design: Diagnostic accuracy study. Methods: Forty-six women with 58 breast masses (35 malignant, 23 benign) were examined on a 1.5 T clinical MRI scanner. The morphologic characteristics of the lesions on conventional MRI sequences and contrast uptake pattern were assessed. ADC values of both lesions and normal breast parenchyma were measured. The ADC values obtained were statistically compared with the histopathologic results using Paired Samples t-Test. Results: Multiple lesions were detected in 12 (26%) of the patients, while only one lesion was detected in 34 (74%). Overall, 35 lesions out of 58 were histopathologically proven to be malignant. In the dynamic contrast-enhanced series, 5 of the malignant lesions were type 1, while 8 benign lesions revealed either type 2 or 3 time signal intensity curves (85% sensitivity, 56% spesifity). Mean ADC values were significantly different in malignant vs. benign lesions. (1.04±0.29×10−3 cm2/sec vs. 1.61±0.50×10−3 cm2/sec for the malignant and benign lesions, respectively, p=0.03). A cut-off value of 1.30×10−3 mm2/sec for ADC detected with receiver operating characteristic analysis yielded 89.1% sensitivity and 100% specificity for the differentiation between benign and malignant lesions. Conclusion: ADC values improve the diagnostic accuracy of solid breast lesions when evaluated with the conventional MRI sequences. Therefore, DWI should be incorporated to routine breast MRI protocol. PMID:27308073

  14. Up-regulated expression of scavenger receptor class B type 1 (SR-B1) is associated with malignant behaviors and poor prognosis of breast cancer.

    PubMed

    Li, Juan; Wang, Jing; Li, Ming; Yin, Linlin; Li, Xiang-An; Zhang, Ting-Guo

    2016-06-01

    Scavenger receptor class B type 1 (SR-B1) is an integral membrane protein that is expressed in numerous cells and tissue types. The primary role of SR-B1 is to facilitate uptake of cholesteryl esters from high-density lipoproteins (HDL) in the liver. Altered SR-B1 expression contributes to human diseases. This study assessed association of SR-B1 expression in breast tissue specimens with breast cancer development and prognosis. Tissue specimens from 30 cases of adjacent normal breast tissues, ductal carcinoma in situ (DCIS) and invasive ductal breast cancer (IDCA) were subjected to Western blot analysis, and 135 cases of DCIS and IDCA were used for quantitative immunohistochemical analysis of SR-B1 expression. The data showed that SR-B1 was significantly overexpressed in IDCA tissues compared to normal breast and DCIS tissues. SR-B1 expression was associated with pre-menopausal status, tumor size, and worse overall survival of patients. The data from this ex vivo study suggests that up-regulated SR-B1 protein expression is associated with malignant behaviors of breast cancer and that SR-B1 is an independent predictor for poor survival in breast cancer patients. PMID:27067809

  15. Breast Tissue 3D Segmentation and Visualization on MRI

    PubMed Central

    Cui, Xiangfei; Sun, Feifei

    2013-01-01

    Tissue segmentation and visualization are useful for breast lesion detection and quantitative analysis. In this paper, a 3D segmentation algorithm based on Kernel-based Fuzzy C-Means (KFCM) is proposed to separate the breast MR images into different tissues. Then, an improved volume rendering algorithm based on a new transfer function model is applied to implement 3D breast visualization. Experimental results have been shown visually and have achieved reasonable consistency. PMID:23983676

  16. Phyllodes Tumor of the Breast With Malignant Melanoma Component: A Case Report.

    PubMed

    Vergine, Marco; Guy, Catherine; Taylor, Mark R

    2015-09-01

    Phyllodes tumors of the breast display a wide variation in histological appearance and are classified into benign, borderline, and malignant categories based on a combination of histological parameters. These tumors may include a malignant heterologous component that is believed to originate through a process of multidirectional differentiation from a cancer stem cell. In these cases, the tumor is classified as a malignant phyllodes tumor. Among the heterologous elements that have been described in malignant phyllodes tumors are rhabdomyosarcoma, chondrosarcoma, osteosarcoma, liposarcoma and angiosarcoma. We present the first case of a phyllodes tumor with a malignant melanoma component in the breast of a 71-year-old lady, discussing the clinical implications of this diagnosis. PMID:26113664

  17. Metastatic Invasive Lobular Carcinoma of the Breast Masquerading as a Primary Renal Malignancy

    PubMed Central

    Al-Jarrah, Adil; Taranikanti, Varna; Sawhney, Sukhpal; Furrukh, Muhammad; Al-Hosni, Mohammad; Saparamadu, P. A. M.; De Silva, M. V. C.

    2013-01-01

    Breast cancer is known to metastasise to different organs in the body, but an initial presentation of breast cancer with loin pain secondary to a metastatic renal mass is extremely rare. We report a 58-year-old woman who presented with recurrent left loin pain due to a metastatic deposit of invasive lobular carcinoma of the breast. The detection of a renal mass on computed tomography led to the assumption of a renal pelvic malignancy. The diagnostic dilemma posed by the detection of a breast mass during staging and the usefulness of immunohistochemistry in the confirmation of diagnosis are discussed. PMID:23984034

  18. Breast metastases from a malignant peripheral nerve sheath tumor of the kidney: An unusual presentation

    PubMed Central

    Koppisetty, Shalini; Alessio, Ricardo C.; Rajpurkar, Atul

    2016-01-01

    Malignant peripheral nerve sheath tumors (MPNSTs) are extremely rare soft tissue sarcomas of ectomesenchymal origin. They are commonly seen in association with neurofibromatosis type 1 (NF-1), but can also occur without a history of NF (isolated MPNST). MPNSTs are most commonly located on the extremities (brachial and sacral plexus), head and neck, and trunk regions and are rarely reported in genitourinary organs. These tumors are aggressive, with a high recurrence rate and distant metastases. MPNST involving the kidney is extremely rare, and review of the literature using PubMed from 2001 to 2014 revealed eight cases of MPNST involving the kidney (seven, primarily involving the kidney and one metastatic MPNST of the kidney). Herein, we describe a case of breast metastases from an MPNST of the kidney without a history of NF-1. The patient was initially diagnosed with a spindle cell neoplasm of the kidney with peripheral nerve sheath differentiation. Eventually, the patient developed a right breast mass that was diagnosed as metastatic MPNST. The patient refused any kind of treatment and died 6 months later in hospice care. PMID:27453670

  19. Butyrate modulates antioxidant enzyme expression in malignant and non-malignant human colon tissues.

    PubMed

    Jahns, Franziska; Wilhelm, Anne; Jablonowski, Nadja; Mothes, Henning; Greulich, Karl Otto; Glei, Michael

    2015-04-01

    The induction of antioxidant enzymes is an important mechanism in colon cancer chemoprevention, but the response of human colon tissue to butyrate, a gut fermentation product derived from dietary fiber, remains largely unknown. Therefore, our study investigated the effect of a butyrate treatment on catalase (CAT) and superoxide dismutase (SOD2) in matched human colon tissues of different transformation stages (n = 3-15 in each group) ex vivo. By performing quantitative real-time PCR, Western blot, and spectrophotometric measurements, we found an increase in SOD2 at expression and activity level in colonic adenocarcinomas (mRNA: 1.96-fold; protein: 1.41-fold, activity: 1.8-fold; P < 0.05). No difference was detectable for CAT between normal, adenoma, and carcinoma colon tissues. Treatment of normal colon epithelium (12 h) with a physiologically relevant concentration of butyrate (10 mM) resulted in a significant increase (P < 0.05) in CAT mRNA (1.24-fold) and protein (1.39-fold), without affecting the enzymatic activity. Consequently, preliminary experiments failed to show any protective effect of butyrate against H2 O2 -mediated DNA damage. Despite a significantly lowered SOD2 transcript (0.51-fold, P < 0.01) and, to a lesser extent, protein level (0.86-fold) after butyrate exposure of normal colon cells, the catalytic activity was significantly enhanced (1.19-fold, P < 0.05), suggesting an increased protection against tissue superoxide radicals. In malignant tissues, greater variations in response to butyrate were observed. Furthermore, both enzymes showed an age-dependent decrease in activity in normal colon epithelium (CAT: r = -0.49, P = 0.09; SOD2: r = -0.58, P = 0.049). In conclusion, butyrate exhibited potential antioxidant features ex vivo but cellular consequences need to be investigated more in depth. PMID:24677319

  20. Extremely rare presentation of soft tissue metastasis from carcinoma breast as a massive swelling of upper extremity.

    PubMed

    Purkayastha, Abhishek; Sharma, Neelam

    2016-04-01

    Soft tissue metastasis from any primary malignancy is considered very rare and a breast carcinoma metastasizing to soft tissue is still rarer. To the best of our knowledge, carcinoma breast with soft tissue metastasis to upper extremity is very uncommon with only six cases been reported in world literature till date and our case is the seventh such case in an 80-year-old female, previously treated for carcinoma right breast 15 years ago. The patient presented with progressive painful massive swelling of right upper arm measuring 21 cm × 17 cm, of 2 months duration. Histopathological examination of the swelling showed metastatic deposits from a poorly differentiated adenocarcinoma. Further immunohistochemical (IHC) analysis revealed tumor cells staining positive for estrogen and progesterone receptors while negative for HER 2-Nu, desmin, epithelial membrane antigen, CK7 and thyroid transcription factor-1 (TTF-1), suggestive of metastasis from a primary breast carcinoma. Only few case series and isolated cases reports have been published regarding any primary malignancy or breast carcinoma metastasizing to soft tissues. A thorough review of literature also reveals that our case is the largest soft tissue metastatic swelling from breast carcinoma ever reported. We hereby present this case with review of literature to highlight its extreme rarity, unusual presentation, clinicopathological characteristics and its overall prognosis. PMID:27121743

  1. Methods for Culturing Human Femur Tissue Explants to Study Breast Cancer Cell Colonization of the Metastatic Niche

    PubMed Central

    Templeton, Zachary S.; Bachmann, Michael H.; Alluri, Rajiv V.; Maloney, William J.; Contag, Christopher H.; King, Bonnie L.

    2015-01-01

    Bone is the most common site of breast cancer metastasis. Although it is widely accepted that the microenvironment influences cancer cell behavior, little is known about breast cancer cell properties and behaviors within the native microenvironment of human bone tissue.We have developed approaches to track, quantify and modulate human breast cancer cells within the microenvironment of cultured human bone tissue fragments isolated from discarded femoral heads following total hip replacement surgeries. Using breast cancer cells engineered for luciferase and enhanced green fluorescent protein (EGFP) expression, we are able to reproducibly quantitate migration and proliferation patterns using bioluminescence imaging (BLI), track cell interactions within the bone fragments using fluorescence microscopy, and evaluate breast cells after colonization with flow cytometry. The key advantages of this model include: 1) a native, architecturally intact tissue microenvironment that includes relevant human cell types, and 2) direct access to the microenvironment, which facilitates rapid quantitative and qualitative monitoring and perturbation of breast and bone cell properties, behaviors and interactions. A primary limitation, at present, is the finite viability of the tissue fragments, which confines the window of study to short-term culture. Applications of the model system include studying the basic biology of breast cancer and other bone-seeking malignancies within the metastatic niche, and developing therapeutic strategies to effectively target breast cancer cells in bone tissues. PMID:25867136

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

    NASA Astrophysics Data System (ADS)

    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 (<μs‧>), 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 <μs‧> and % collagen and a negative correlation between <μs‧> and age and BMI. Increased collagen corresponded to increased <μs‧> variability. In postmenopausal women, <μs‧> was similar regardless of fibroglandular content. Contributions from collagen and glands to <μs‧> were independent and equivalent in benign sites; glands showed a stronger positive correlation than collagen to <μs‧> 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.

  3. Differentiation of Benign and Malignant Breast Tumors by In-Vivo Three-Dimensional Parallel-Plate Diffuse Optical Tomography

    PubMed Central

    Choe, Regine; Konecky, Soren D.; Corlu, Alper; Lee, Kijoon; Durduran, Turgut; Busch, David R.; Pathak, Saurav; Czerniecki, Brian J.; Tchou, Julia; Fraker, Douglas L.; DeMichele, Angela; Chance, Britton; Arridge, Simon R.; Schweiger, Martin; Culver, Joseph P.; Schnall, Mitchell D.; Putt, Mary E.; Rosen, Mark A.; Yodh, Arjun G.

    2009-01-01

    We have developed a novel parallel-plate diffuse optical tomography (DOT) system for three-dimensional in vivo imaging of human breast tumor based on large optical data sets. Images of oxy-, deoxy-, total-hemoglobin concentration, blood oxygen saturation, and tissue scattering were reconstructed. Tumor margins were derived using the optical data with guidance from radiology reports and Magnetic Resonance Imaging. Tumor-to-normal ratios of these endogenous physiological parameters and an optical index were computed for 51 biopsy-proven lesions from 47 subjects. Malignant cancers (N=41) showed statistically significant higher total hemoglobin, oxy-hemoglobin concentration, and scattering compared to normal tissue. Furthermore, malignant lesions exhibited a two-fold average increase in optical index. The influence of core biopsy on DOT results was also explored; the difference between the malignant group measured before core biopsy and the group measured more than one week after core biopsy was not significant. Benign tumors (N=10) did not exhibit statistical significance in the tumor-to-normal ratios of any parameter. Optical index and tumor-to-normal ratios of total hemoglobin, oxy-hemoglobin concentration, and scattering exhibited high area under the receiver operating characteristic curve values from 0.90 to 0.99, suggesting good discriminatory power. The data demonstrate that benign and malignant lesions can be distinguished by quantitative three-dimensional DOT. PMID:19405750

  4. Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography

    NASA Astrophysics Data System (ADS)

    Choe, Regine; Konecky, Soren D.; Corlu, Alper; Lee, Kijoon; Durduran, Turgut; Busch, David R.; Pathak, Saurav; Czerniecki, Brian J.; Tchou, Julia; Fraker, Douglas L.; Demichele, Angela; Chance, Britton; Arridge, Simon R.; Schweiger, Martin; Culver, Joseph P.; Schnall, Mitchell D.; Putt, Mary E.; Rosen, Mark A.; Yodh, Arjun G.

    2009-03-01

    We have developed a novel parallel-plate diffuse optical tomography (DOT) system for three-dimensional in vivo imaging of human breast tumor based on large optical data sets. Images of oxy-, deoxy-, and total hemoglobin concentration as well as blood oxygen saturation and tissue scattering were reconstructed. Tumor margins were derived using the optical data with guidance from radiology reports and magnetic resonance imaging. Tumor-to-normal ratios of these endogenous physiological parameters and an optical index were computed for 51 biopsy-proven lesions from 47 subjects. Malignant cancers (N=41) showed statistically significant higher total hemoglobin, oxy-hemoglobin concentration, and scattering compared to normal tissue. Furthermore, malignant lesions exhibited a twofold average increase in optical index. The influence of core biopsy on DOT results was also explored; the difference between the malignant group measured before core biopsy and the group measured more than 1 week after core biopsy was not significant. Benign tumors (N=10) did not exhibit statistical significance in the tumor-to-normal ratios of any parameter. Optical index and tumor-to-normal ratios of total hemoglobin, oxy-hemoglobin concentration, and scattering exhibited high area under the receiver operating characteristic curve values from 0.90 to 0.99, suggesting good discriminatory power. The data demonstrate that benign and malignant lesions can be distinguished by quantitative three-dimensional DOT.

  5. Large Malignant Phyllodes Tumor of the Breast with Metastases to the Lungs.

    PubMed

    Augustyn, Alexander; Sahoo, Sunati; Wooldridge, Rachel D

    2015-05-01

    Phyllodes tumors of the breast account for less than 0.5% of breast cancers and present most commonly in women 45 to 49 years old. The importance in managing fibroepithelial lesions lies in distinguishing fibroadenomas, which are benign, from phyllodes tumors, which can be malignant and require complete surgical excision. We report the case of a 56-year-old female who presented with a rapidly enlarging mass in her right breast 18 cm in maximum dimension that completely effaced the breast and distorted the nipple. The patient underwent a successful total mastectomy after core biopsy revealed a diagnosis of phyllodes tumor. Surgical resection is the primary treatment modality; neoadjuvant and adjuvant therapies remain controversial. Here, we report the case of a large malignant phyllodes tumor metastatic to the lungs, review the literature, and discuss diagnostic modalities and adjunct nonsurgical therapies. PMID:26266007

  6. Comparison of Breast Cancer to Healthy Control Tissue Discovers Novel Markers with Potential for Prognosis and Early Detection

    PubMed Central

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

    2010-01-01

    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. PMID:20161755

  7. Synchronous bilateral primary breast malignant phyllodes tumor and carcinoma of the breast with Paget’s disease: a case report and review of the literature

    PubMed Central

    Zhao, Hongyuan; Cheng, Xiaoming; Sun, Suhong; Yang, Weiming; Kong, Fanli; Zeng, Feng

    2015-01-01

    Synchronous bilateral primary breast malignant phyllodes tumor or/and carcinoma of the breast with Paget’s disease is rare. In the article, we present a case of bilateral carcinoma of the breast with Paget’s disease of the right breast and malignant phyllodes tumor of the left breast. A 44-years-old Chinese woman presented with a 1 month history of the right breast nipple with eczema and fester and growing and palpable mass of left breast. Molybdenum target X-ray revealed microcalcification in the right breast, which was highly suspected of malignant tumor, and round-like mass with smooth surface and homogeneous density in the left breast. Color ultrasound showed a lobulated lump which circumferential blood flows around in the left breast, and which did not show any mass in the right breast. The patient was undertaken the bilateral modified radical mastectomy. The histological diagnosis was Paget’s disease associated with infiltrating ductal carcinoma in the right breast and malignant phyllodes tumor the left breast. The patient also received 6 cycles of the postoperative adjuvant chemotherapy by using T.T. regimen comprised docetaxel (100 mg) and pirarubicin (60 mg). PMID:26770378

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

    PubMed

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

    2016-01-21

    Fourier Transform InfraRed (FTIR) spectroscopy coupled to microscopy (IR imaging) has shown unique advantages in detecting morphological and molecular pathologic alterations in biological tissues. The aim of this study was to evaluate the potential of IR imaging as a diagnostic tool to identify characteristics of breast epithelial cells and the stroma. In this study a total of 19 breast tissue samples were obtained from 13 patients. For 6 of the patients, we also obtained Non-Adjacent Non-Tumor tissue samples. Infrared images were recorded on the main cell/tissue types identified in all breast tissue samples. Unsupervised Principal Component Analyses and supervised Partial Least Square Discriminant Analyses (PLS-DA) were used to discriminate spectra. Leave-one-out cross-validation was used to evaluate the performance of PLS-DA models. Our results show that IR imaging coupled with PLS-DA can efficiently identify the main cell types present in FFPE breast tissue sections, i.e. epithelial cells, lymphocytes, connective tissue, vascular tissue and erythrocytes. A second PLS-DA model could distinguish normal and tumor breast epithelial cells in the breast tissue sections. A patient-specific model reached particularly high sensitivity, specificity and MCC rates. Finally, we showed that the stroma located close or at distance from the tumor exhibits distinct spectral characteristics. In conclusion FTIR imaging combined with computational algorithms could be an accurate, rapid and objective tool to identify/quantify breast epithelial cells and differentiate tumor from normal breast tissue as well as normal from tumor-associated stroma, paving the way to the establishment of a potential complementary tool to ensure safe tumor margins. PMID:26535413

  9. Intravoxel Incoherent Motion Diffusion-Weighted MRI at 3.0 T Differentiates Malignant Breast Lesions From Benign Lesions and Breast Parenchyma

    PubMed Central

    Bokacheva, Louisa; Kaplan, Jennifer B.; Giri, Dilip D.; Patil, Sujata; Gnanasigamani, Merlin; Nyman, C. Gregory; Deasy, Joseph O.; Morris, Elizabeth A.; Thakur, Sunitha B.

    2016-01-01

    Purpose To study the differentiation of malignant breast lesions from benign lesions and fibroglandular tissue (FGT) using apparent diffusion coefficient (ADC) and intravoxel incoherent motion (IVIM) parameters. Materials and Methods This retrospective study included 26 malignant and 14 benign breast lesions in 35 patients who underwent diffusion-weighted MRI at 3.0T and nine b-values (0–1000 s/mm2). ADC and IVIM parameters (perfusion fraction fp, pseudodiffusion coefficient Dp, and true diffusion coefficient Dd) were determined in lesions and FGT. For comparison, IVIM was also measured in 16 high-risk normal patients. A predictive model was constructed using linear discriminant analysis. Lesion discrimination based on ADC and IVIM parameters was assessed using receiver operating characteristic (ROC) and area under the ROC curve (AUC). Results In FGT of normal subjects, fp was 1.1 ± 1.1%. In malignant lesions, fp (6.4 ± 3.1%) was significantly higher than in benign lesions (3.1 ± 3.3%, P = 0.0025) or FGT (1.5 ± 1.2%, P < 0.001), and Dd ((1.29 ± 0.28) × 10−3 mm2/s) was lower than in benign lesions ((1.56 ± 0.28) × 10−3 mm2/s, P = 0.011) or FGT ((1.86 ± 0.34) × 10−3 mm2/s, P < 0.001). A combination of Dd and fp provided higher AUC for discrimination between malignant and benign lesions (0.84) or FGT (0.97) than ADC (0.72 and 0.86, respectively). Conclusion The IVIM parameters provide accurate identification of malignant lesions. PMID:24273096

  10. Malignant myoepithelioma of soft tissue: a case report with cytogenetic findings.

    PubMed

    Balogh, Zsófia; Deák, Linda; Sápi, Zoltán

    2008-06-01

    Soft tissue malignant myoepithelioma (STMM) is a particularly rare tumor displaying myoepithelial elements and lacking obvious ductal differentiation. From the one case report with cytogenetic data available in the literature, STMM seems to be a distinct entity with some resemblance to chordoma on the one hand and myoepithelioma on the other. The present case of STMM yielded novel data from high-resolution comparative genomic hybridization (HR-CGH) analysis. An 82-year-old female patient presented with a soft tissue tumor within the deep soft tissues in the right gluteal muscle measuring 16 x 13 x 11 cm. Histologically, the lesion was diagnosed as a myoepithelial carcinoma. Immunohistochemistry was focally positive for pancytokeratin, EMA, S-100 protein, and alpha smooth muscle actin. HR-CGH analysis revealed gains of 1p31 approximately p34, 1q21 approximately q23, 9q12 approximately q33, and 16q22 and losses of 1p11 approximately p22, 1q24 approximately q44, 3p, 10q11.1 approximately q22, 13q, 14q13 approximately q24, and 15q. Subsequent fluorescence in situ hybridization analysis confirmed deletion of 3p, gain of 16q, and monosomy of chromosomes 13 and 15. These results support the hypothesis that STMM is a distinct entity, not sharing the cytogenetic alterations of salivary gland myoepithelial carcinomas and ductal carcinomas of breast with myoepithelial differentiation. PMID:18503832

  11. Pitfalls in oncology: a unique case of thoracic splenosis mimicking malignancy in a patient with resected breast cancer

    PubMed Central

    Castellani, Maria Rita; Marchianò, Alfonso; Duca, Matteo; Mariani, Paola; Aliberti, Gianluca; Maccauro, Marco; Duranti, Leonardo; Capri, Giuseppe; de Braud, Filippo Guglielmo; Bianchi, Giulia Valeria

    2016-01-01

    Thoracic splenosis (TS) is a condition of autotransplantation of splenic tissue into the pleural cavity after thoraco-abdominal trauma, with diaphragmatic and spleen injury. It is usually asymptomatic and discovered as an incidental finding at imaging performed for other reasons. Its differential diagnosis regards different benign and malignant conditions and should be discerned avoiding invasive procedures. We report a case of thoracic mass associated with pleural nodules mimicking malignancy in a patient with resected breast cancer for whom a diagnosis of TS was made early by using non-invasive methods. Briefly, we review the literature data on TS, comment concisely the possible implications of using invasive procedures and describe the current non-invasive techniques available. Furthermore, we highlight the importance of an accurate medical history collection, the role of the multidisciplinary board and their impact on treatment decision making. Finally, we conclude that clinical information and imaging would be the discriminating factors to avoid unnecessary invasive procedures. PMID:27293867

  12. Pitfalls in oncology: a unique case of thoracic splenosis mimicking malignancy in a patient with resected breast cancer.

    PubMed

    Gelsomino, Francesco; Castellani, Maria Rita; Marchianò, Alfonso; Duca, Matteo; Mariani, Paola; Aliberti, Gianluca; Maccauro, Marco; Duranti, Leonardo; Capri, Giuseppe; de Braud, Filippo Guglielmo; Bianchi, Giulia Valeria

    2016-06-01

    Thoracic splenosis (TS) is a condition of autotransplantation of splenic tissue into the pleural cavity after thoraco-abdominal trauma, with diaphragmatic and spleen injury. It is usually asymptomatic and discovered as an incidental finding at imaging performed for other reasons. Its differential diagnosis regards different benign and malignant conditions and should be discerned avoiding invasive procedures. We report a case of thoracic mass associated with pleural nodules mimicking malignancy in a patient with resected breast cancer for whom a diagnosis of TS was made early by using non-invasive methods. Briefly, we review the literature data on TS, comment concisely the possible implications of using invasive procedures and describe the current non-invasive techniques available. Furthermore, we highlight the importance of an accurate medical history collection, the role of the multidisciplinary board and their impact on treatment decision making. Finally, we conclude that clinical information and imaging would be the discriminating factors to avoid unnecessary invasive procedures. PMID:27293867

  13. Malignant transformation of Madelung’s disease in a patient with a coincidental diagnosis of breast cancer: a case report

    PubMed Central

    2012-01-01

    Abstract Madelung’s disease or multiple symmetric lipomatosis (MSL) is a rare disorder of unknown etiology which typically presents symmetrically subcutaneous accumulation of non-encapsulated adipose tissue which slowly grows around the neck, upper part of the arms, pelvis, back and thigh. This disease is also frequently associated with hepatopathy, glucose intolerance, hyperuricemia, and malignant tumors of the upper airways. Nevertheless, only one description of malignant transformation of Madelung’s disease has been presented in literature. Here, we report a case of liposarcomatous transformation of Madelung’s disease in a 59-year-old Italian woman with a coincidental diagnosis of breast cancer. Virtual slide The virtual slide for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3480884087499351 PMID:22937763

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

    MedlinePlus

    ... Denser Breast Tissue Previous research has linked higher density to increased risk of breast cancer To use ... reported data about diet. They also rated the density of the women's breast tissue as seen on ...

  15. Development of a cryosurgical technique for breast malignancies

    NASA Astrophysics Data System (ADS)

    Rabin, Yoed; Julian, Thomas B.; Olson, Peter; Taylor, Michael J.; Wolmark, Norman

    1999-06-01

    Carcinoma of the breast continues to be the second major cause of death in women in the US today, with 180,000 new cases detected annually in the US. One third of these carcinomas are 1 cm in size or less. The current techniques of surgical resection require operating rooms, anesthesia, cosmetic concerns and cost. The benefits of cryosurgery for the treatment of visceral tumors has stimulated the investigation of this approach for carcinomas of the breast. Here within is a work-in-progress report of our research program to evaluate a cryodevice and techniques for breast cryosurgery.

  16. Primary inflammatory malignant fibrous histiocytoma of the breast: a case report of an unusual variant and review of the literature.

    PubMed

    Tashjian, Randy; Gilani, Syed M; Falk, Jeffery; Kelly, Michael J; Ockner, Daniel; Danforth, Robert

    2013-08-01

    Malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma of adults, but its presence in the breast is rare. We report a case of primary inflammatory MFH in a 72-year-old Caucasian female with no previous medical history and no prior radiation exposure. She presented with a palpable mass that was suspicious for malignancy on mammography. Histologic evaluation of the core needle biopsy revealed sheets of large, pleomorphic neoplastic cells within a dense background of acute and chronic inflammatory cells. The neoplastic cells exhibited a moderate to abundant amount of finely vacuolated cytoplasm and atypical nuclei with vesicular nuclear chromatin and prominent nucleoli. Mitotic activity was readily identified, and foci of necrosis were noted. The neoplastic cells were immunoreactive with CD68, alpha 1-antitrypsin, alpha 1-antichymotrypsin, and vimentin. The diagnosis of MFH was rendered after thorough microscopic examination of the entire mass following mastectomy. MFH of the breast is a diagnosis of exclusion. The definitive treatment of MFH is surgical, either with wide local excision or total mastectomy. The roles of sentinel lymph node biopsy, axillary lymph node dissection, chemotherapy, and radiation have yet to be definitively clarified. The prognosis of MFH of the breast is generally poor. PMID:23827212

  17. Roles of biologic breast tissue composition and quantitative image analysis of mammographic images in breast tumor characterization

    NASA Astrophysics Data System (ADS)

    Drukker, Karen; Giger, Maryellen L.; Duewer, Fred; Malkov, Serghei; Flowers, Christopher I.; Joe, Bonnie; Kerlikowske, Karla; Drukteinis, Jennifer S.; Shepherd, John

    2014-03-01

    Purpose. Investigate whether knowledge of the biologic image composition of mammographic lesions provides imagebased biomarkers above and beyond those obtainable from quantitative image analysis (QIA) of X-ray mammography. Methods. The dataset consisted of 45 in vivo breast lesions imaged with the novel 3-component breast (3CB) imaging technique based on dual-energy mammography (15 malignant, 30 benign diagnoses). The 3CB composition measures of water, lipid, and protein thicknesses were assessed and mathematical descriptors, `3CB features', were obtained for the lesions and their periphery. The raw low-energy mammographic images were analyzed with an established in-house QIA method obtaining `QIA features' describing morphology and texture. We investigated the correlation within the `3CB features', within the `QIA features', and between the two. In addition, the merit of individual features in the distinction between malignant and benign lesions was assessed. Results. Whereas many descriptors within the `3CB features' and `QIA features' were, often by design, highly correlated, correlation between descriptors of the two feature groups was much weaker (maximum absolute correlation coefficient 0.58, p<0.001) indicating that 3CB and QIA-based biomarkers provided potentially complementary information. Single descriptors from 3CB and QIA appeared equally well-suited for the distinction between malignant and benign lesions, with maximum area under the ROC curve 0.71 for a protein feature (3CB) and 0.71 for a texture feature (QIA). Conclusions. In this pilot study analyzing the new 3CB imaging modality, knowledge of breast tissue composition appeared additive in combination with existing mammographic QIA methods for the distinction between benign and malignant lesions.

  18. Rates of Second Malignancies After Definitive Local Treatment for Ductal Carcinoma In Situ of the Breast

    SciTech Connect

    Shaitelman, Simona F.; Grills, Inga S.; Kestin, Larry L.; Ye Hong; Nandalur, Sirisha; Huang Jiayi; Vicini, Frank A.

    2011-12-01

    Purpose: We analyzed the risk of second malignancies developing in patients with ductal carcinoma in situ (DCIS) undergoing surgery and radiotherapy (S+RT) vs. surgery alone. Methods and Materials: The S+RT cohort consisted of 256 women treated with breast-conserving therapy at William Beaumont Hospital. The surgery alone cohort consisted of 2,788 women with DCIS in the regional Surveillance, Epidemiology, and End Results database treated during the same time period. A matched-pair analysis was performed in which each S+RT patient was randomly matched with 8 surgery alone patients (total of 2,048 patients). Matching criteria included age {+-} 2 years. The rates of second malignancies were analyzed overall and as contralateral breast vs. non-breast cancers and by organ system. Results: Median follow-up was 13.7 years for the S+RT cohort and 13.3 years for the surgery alone cohort. The overall 10-/15-year rates of second malignancies among the S+RT and surgery alone cohorts were 14.2%/24.2% and 16.4%/22.6%, respectively (p = 0.668). The 15-year second contralateral breast cancer rate was 14.2% in the S+RT cohort and 10.3% in the surgery alone cohort (p = 0.439). The 15-year risk of a second non-breast malignancy was 14.2% for the S+RT cohort and 13.4% for the surgery alone cohort (p = 0.660). When analyzed by organ system, the 10- and 15-year rates of second malignancies did not differ between the S+RT and surgery alone cohorts for pulmonary, gastrointestinal, central nervous system, gynecologic, genitourinary, lymphoid, sarcomatoid, head and neck, or unknown primary tumors. Conclusions: Compared with surgery alone, S+RT is not associated with an overall increased risk of second malignancies in women with DCIS.

  19. Axial Shear Strain Imaging for Differentiating Benign and Malignant Breast Masses

    PubMed Central

    Xu, Haiyan; Rao, Min; Varghese, Tomy; Sommer, Amy; Baker, Sara; Hall, Timothy J; Sisney, Gale A; Burnside, Elizabeth S

    2010-01-01

    Axial strain imaging has been utilized for the characterization of breast masses for over a decade; however, another important feature namely the shear strain distribution around breast masses has only recently been used. In this paper, we examine the feasibility of utilizing in-vivo axial-shear strain imaging for differentiating benign from malignant breast masses. Radiofrequency data was acquired using a VFX 13-5 linear array transducer on 41 patients using a Siemens SONOLINE Antares real-time clinical scanner at the University of Wisconsin Breast Cancer Center. Free-hand palpation using deformations of up to 10% was utilized to generate axial strain and axial-shear strain images using a two-dimensional cross-correlation algorithm from the radiofrequency data loops. Axial-shear strain areas normalized to the lesion size, applied strain and lesion strain contrast was utilized as a feature for differentiating benign from malignant masses. The normalized axial-shear strain area feature estimated on 8 patients with malignant tumors and 33 patients with fibroadenomas was utilized to demonstrate its potential for lesion differentiation. Biopsy results were considered the diagnostic standard for comparison. Our results indicate that the normalized axial-shear strain area is significantly larger for malignant tumors when compared to benign masses such as fibroadenomas. Axial-shear strain pixel values greater than a specified threshold, including only those with correlation coefficient values greater than 0.75, were overlaid on the corresponding B-mode image to aid in diagnosis. A scatter plot of the normalized area feature demonstrates the feasibility of developing a linear classifier to differentiate benign from malignant masses. The area under the receiver operator characteristic curve utilizing the normalized axial-shear strain area feature was 0.996, demonstrating the potential of this feature to noninvasively differentiate between benign and malignant breast masses

  20. Monte Carlo-based inverse model for calculating tissue optical properties. Part II: Application to breast cancer diagnosis

    NASA Astrophysics Data System (ADS)

    Palmer, Gregory M.; Zhu, Changfang; Breslin, Tara M.; Xu, Fushen; Gilchrist, Kennedy W.; Ramanujam, Nirmala

    2006-02-01

    The Monte Carlo-based inverse model of diffuse reflectance described in part I of this pair of companion papers was applied to the diffuse reflectance spectra of a set of 17 malignant and 24 normal-benign ex vivo human breast tissue samples. This model allows extraction of physically meaningful tissue parameters, which include the concentration of absorbers and the size and density of scatterers present in tissue. It was assumed that intrinsic absorption could be attributed to oxygenated and deoxygenated hemoglobin and beta-carotene, that scattering could be modeled by spheres of a uniform size distribution, and that the refractive indices of the spheres and the surrounding medium are known. The tissue diffuse reflectance spectra were evaluated over a wavelength range of 400-600 nm. The extracted parameters that showed the statistically most significant differences between malignant and nonmalignant breast tissues were hemoglobin saturation and the mean reduced scattering coefficient. Malignant tissues showed decreased hemoglobin saturation and an increased mean reduced scattering coefficient compared with nonmalignant tissues. A support vector machine classification algorithm was then used to classify a sample as malignant or nonmalignant based on these two extracted parameters and produced a cross-validated sensitivity and specificity of 82% and 92%, respectively.

  1. Atlas-Based Probabilistic Fibroglandular Tissue Segmentation in Breast MRI

    PubMed Central

    Wu, Shandong; Weinstein, Susan; Kontos, Despina

    2014-01-01

    In this paper we propose an atlas-aided probabilistic model-based segmentation method for estimating the fibroglandular tissue in breast MRI, where a novel fibroglandular tissue atlas is learned to aid the segmentation. The atlas represents a pixel-wise likelihood of being fibroglandular tissue in the breast, which is derived by combining deformable image warping, using aligned breast contour points as landmarks, with a kernel density estimation technique. A mixture multivariate model is learned to characterize the breast tissue using MR image features, and the segmentation is subsequently based on examining the posterior probability where the learned atlas is incorporated as the prior probability. In our experiments, the algorithm-generated segmentation results of 10 cases are compared to the manual segmentations, verified by an experienced breast imaging radiologist, to assess the accuracy of the algorithm, where the Dice’s Similarity Coefficient (DSC) shows a 0.85 agreement. The proposed automated segmentation method could be used to estimate the volumetric amount of fibroglandular tissue in the breast for breast cancer risk estimation. PMID:23286078

  2. Correlations of trace elements in breast human tissues: Evaluation of spatial distribution using μ-XRF

    NASA Astrophysics Data System (ADS)

    Silva, Marina Piacenti da; Silva, Deisy Mara da; Ribeiro-Silva, Alfredo; Poletti, Martin Eduardo

    2012-05-01

    The aim of this work is to investigate microscopic correlations between trace elements in breast human tissues. A synchrotron X-ray fluorescence microprobe system (μ-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 Laboratório Nacional de Luz Síncrotron (LNLS), Campinas, Brazil. The white microbeam was generated with a fine conical capillary with a 20 μm 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 μm 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.

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

    SciTech Connect

    Piacenti da Silva, Marina; Silva, Deisy Mara da; Ribeiro-Silva, Alfredo; Poletti, Martin Eduardo

    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.

  4. Primary angiosarcoma of breast: a case report.

    PubMed

    Raju, K V V N; Mahajan, Munish; Rehmani, Kabir; Pawar, Satish; Murthy, Sudha S

    2014-06-01

    Primary breast sarcomas are rare entities. These malignant tumors originate from mesenchymal glandular breast tissue and account for <1 % of all breast cancer cases. Angiosarcomas are rare malignant tumors that arise from endothelial cells lining vascular channels. Most angiosarcomas are secondary to radiotherapy treatments for breast cancer or to an arm lymphoedema subsequent to a modified radical mastectomy. Primary angiosarcomas are rare and account for 0.04 % of all malignant breast tumors. PMID:25114472

  5. Evaluation of breast cancer using intravoxel incoherent motion (IVIM) histogram analysis: comparison with malignant status, histological subtype, and molecular prognostic factors

    PubMed Central

    Cho, Gene Young; Moy, Linda; Kim, Sungheon G.; Baete, Steven H.; Moccaldi, Melanie; Babb, James S.; Sodickson, Daniel K.; Sigmund, Eric E.

    2016-01-01

    Purpose To examine heterogeneous breast cancer through intravoxel incoherent motion (IVIM) histogram analysis. Materials and methods This HIPAA-compliant, IRB-approved retrospective study included 62 patients (age 48.44±11.14 years, 50 malignant lesions and 12 benign) who underwent contrast-enhanced 3 T breast MRI and diffusion-weighted imaging. Apparent diffusion coefficient (ADC) and IVIM biomarkers of tissue diffusivity (Dt), perfusion fraction (fp), and pseudo-diffusivity (Dp) were calculated using voxel-based analysis for the whole lesion volume. Histogram analysis was performed to quantify tumour heterogeneity. Comparisons were made using Mann–Whitney tests between benign/malignant status, histological subtype, and molecular prognostic factor status while Spearman’s rank correlation was used to characterize the association between imaging biomarkers and prognostic factor expression. Results The average values of the ADC and IVIM biomarkers, Dt and fp, showed significant differences between benign and malignant lesions. Additional significant differences were found in the histogram parameters among tumour subtypes and molecular prognostic factor status. IVIM histogram metrics, particularly fp and Dp, showed significant correlation with hormonal factor expression. Conclusion Advanced diffusion imaging biomarkers show relationships with molecular prognostic factors and breast cancer malignancy. This analysis reveals novel diagnostic metrics that may explain some of the observed variability in treatment response among breast cancer patients. PMID:26615557

  6. Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast

    PubMed Central

    Gatalica, Zoran; Vranic, Semir; Ghazalpour, Anatole; Xiu, Joanne; Ocal, Idris Tolgay; McGill, John; Bender, Ryan P.; Discianno, Erin; Schlum, Aaron; Sanati, Souzan; Palazzo, Juan; Reddy, Sandeep; Pockaj, Barbara

    2016-01-01

    Malignant phyllodes tumor is a rare breast malignancy with sarcomatous overgrowth and with limited effective treatment options for recurrent and metastatic cases. Recent clinical trials indicated a potential for anti-angiogenic, anti-EGFR and immunotherapeutic approaches for patients with sarcomas, which led us to investigate these and other targetable pathways in malignant phyllodes tumor of the breast. Thirty-six malignant phyllodes tumors (including 8 metastatic tumors with two cases having matched primary and metastatic tumors) were profiled using gene sequencing, gene copy number analysis, whole genome expression, and protein expression. Whole genome expression analysis demonstrated consistent over-expression of genes involved in angiogenesis including VEGFA, Angiopoietin-2, VCAM1, PDGFRA, and PTTG1. EGFR protein overexpression was observed in 26/27 (96%) of cases with amplification of the EGFR gene in 8/24 (33%) cases. Two EGFR mutations were identified including EGFRvIII and a presumed pathogenic V774M mutation, respectively. The most common pathogenic mutations included TP53 (50%) and PIK3CA (15%). Cases with matched primary and metastatic tumors harbored identical mutations in both sites (PIK3CA/KRAS and RB1 gene mutations, respectively). Tumor expression of PD-L1 immunoregulatory protein was observed in 3/22 (14%) of cases. Overexpression of molecular biomarkers of increased angiogenesis, EGFR and immune checkpoints provides novel targeted therapy options in malignant phyllodes tumors of the breast. PMID:26625196

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    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

  10. Visualization of basement membranes in normal breast and breast cancer tissues using multiphoton microscopy

    PubMed Central

    WU, XIUFENG; CHEN, GANG; QIU, JINGTING; LU, JIANPING; ZHU, WEIFENG; CHEN, JIANXIN; ZHUO, SHUANGMU; YAN, JUN

    2016-01-01

    Since basement membranes represent a critical barrier during breast cancer progression, timely imaging of these signposts is essential for early diagnosis of breast cancer. A label-free method using multiphoton microscopy (MPM) based on two-photon excited fluorescence signals and second harmonic generation signals for analyzing the morphology of basement membrane in normal and cancerous breast tissues is likely to enable a better understanding of the pathophysiology of breast cancer and facilitate improved clinical management and treatment of this disease. The aim of this study was to determine whether MPM has the potential for label-free assessment of the morphology of basement membrane in normal and cancerous breast tissues. A total of 60 tissue section samples (comprising 30 fresh breast cancer specimens and 30 normal breast tissues) were first imaged (fresh, unfixed and unstained) with MPM and are then processed for routine hematoxylin and eosin (H&E) histopathology. Comparisons were made between MPM imaging and gold standard sections for each specimen stained with H&E. Simply by visualizing morphological features appearing on multiphoton images, cancerous lesions may be readily identified by the loss of basement membrane and tumor cells characterized by irregular size and shape, enlarged nuclei and increased nuclear-cytoplasmic ratio. These results suggest that MPM has potential as a label-free method of imaging the morphology of basement membranes and cell features to effectively distinguish between normal and cancerous breast tissues. PMID:27313695

  11. [Pseudo color method for the infrared thermogram display of local breast focus tissue].

    PubMed

    Tang, Xian-Wu; Ding, Hai-Shu; Teng, Yi-Chao

    2009-03-01

    An infrared thermogram which reflects the human body surface temperature distribution can be obtained through detecting the infrared thermal radiation from each point on the human body surface. When a malignant tumor occurs in a breast, it will cause an increase in the prominent temperature in the breast surface focus region due to the abnormal blood transmission state of local focus tissue. Breast cancer can be detected through the visual analysis of the focus regions by physicians. In order to help physicians better find these focus regions, the present paper improved the traditional pseudo color display method by introducing visual effect factor and made the focus regions have a better display effect. The efficacy of this method was verified in the breast infrared thermograms of 47 breast cancer patients. The result from visual analysis of the focus region in infrared thermogram by this method can also be compared with the tissue blood transmission state from near infrared spectroscopy (NIRS) and other methods. It will be helpful to obtain more accurate diagnostic information. PMID:19455784

  12. Optical transillumination spectroscopy of breast tissue for cancer risk assessment

    NASA Astrophysics Data System (ADS)

    Lilge, Lothar; Blyschak, Kristina; Simick, Michelle; Jong, Roberta A.

    2003-10-01

    Breast cancer is the most commonly occurring cancer in women. The lifetime risk of being diagnosed with breast cancer is approximately 1 in 10 thereby the highest out of all cancers. Breast cancer screening programs have been shown to decrease the mortality rates of women between ages 50-69, since cancers are detected at an earlier, more favourable stage. It is apparent that the development of breast cancer is a slow process following initial transformation of the breast tissue. Hence, there has been a strong effort within the research community to understand risk factors for the disease. Risk factors are defined as those characteristics that are more common in people with the disease when compared to the normal population. Quantification of an individual's breast cancer rate may lead that individual to modify her lifestyle and/or diet. Lifestyle changes could lead to a reduction in the incidence of breast cancer. Anatomically, the presence of increased amounts of fibroglandular tissue raises the estimated risk by up to 6 fold (correct for age), hence representing one of the strongest known risk factors pertaining to the entire female population. In this study the relative area of mammographic densities within a mammogram will be used as a global risk assessment tool. It has been shown previously that quantification of water, lipids, haemoglobin and other tissue chromophores of the optically interrogated breast tissue, which also gives rise to the mammographic densities, is feasible through near-infrared spectroscopy. Thus, the hypothesis for this study is that optical transillumination spectroscopy provides consistent and/or complementary information to conventional mammography in quantifying breast tissue density.

  13. Nucleic acid-based tissue biomarkers of urologic malignancies.

    PubMed

    Dietrich, Dimo; Meller, Sebastian; Uhl, Barbara; Ralla, Bernhard; Stephan, Carsten; Jung, Klaus; Ellinger, Jörg; Kristiansen, Glen

    2014-08-01

    Molecular biomarkers play an important role in the clinical management of cancer patients. Biomarkers allow estimation of the risk of developing cancer; help to diagnose a tumor, ideally at an early stage when cure is still possible; and aid in monitoring disease progression. Furthermore, they hold the potential to predict the outcome of the disease (prognostic biomarkers) and the response to therapy (predictive biomarkers). Altogether, biomarkers will help to avoid tumor-related deaths and reduce overtreatment, and will contribute to increased survival and quality of life in cancer patients due to personalized treatments. It is well established that the process of carcinogenesis is a complex interplay between genomic predisposition, acquired somatic mutations, epigenetic changes and genomic aberrations. Within this complex interplay, nucleic acids, i.e. RNA and DNA, play a fundamental role and therefore represent ideal candidates for biomarkers. They are particularly promising candidates because sequence-specific hybridization and amplification technologies allow highly accurate and sensitive assessment of these biomarker levels over a broad dynamic range. This article provides an overview of nucleic acid-based biomarkers in tissues for the management of urologic malignancies, i.e. tumors of the prostate, testis, kidney, penis, urinary bladder, renal pelvis, ureter and other urinary organs. Special emphasis is put on genomic, transcriptomic and epigenomic biomarkers (SNPs, mutations [genomic and mitochondrial], microsatellite instabilities, viral and bacterial DNA, DNA methylation and hydroxymethylation, mRNA expression, and non-coding RNAs [lncRNA, miRNA, siRNA, piRNA, snRNA, snoRNA]). Due to the multitude of published biomarker candidates, special focus is given to the general applicability of different molecular classes as biomarkers and some particularly promising nucleic acid biomarkers. Furthermore, specific challenges regarding the development and clinical

  14. Infrared Spectra of Human Breast Tumor Tissue and Experimental Animal Tumors

    NASA Astrophysics Data System (ADS)

    Tolstorozhev, G. B.; Belkov, M. V.; Skornyakov, I. V.; Pekhnyo, V. I.; Kozachkova, A. N.; Tsarik, H. V.; Kutsenko, I. P.; Sharykina, N. I.; Butra, V. A.

    2015-01-01

    We have used Fourier transform IR spectroscopy methods to conduct comparative studies of human breast tumors and sarcoma 180 tumor grafted into mice. The IR spectral parameters used to identify tumor tissue in mice with the sarcoma 180 strain proved to be identical to the parameters for human breast tissue in cancer. In the presence of a malignant tumor in humans, the most intense C=O vibrational bands in the protein molecules are observed in the interval 1710-1680 cm-1. For a benign tumor, in the IR spectra of breast tissue the intense bands are located in the interval 1670-1650 cm-1. We spectroscopically monitored the diagnosis and the chemotherapy process using the model of sarcoma 180 in mice. As the therapeutic drugs, we used synthesized coordination compounds based on palladium complexes with diphosphonic acid derivatives. We demonstrate the promising potential of palladium complexes with zoledronic acid as an effective cytostatic. In therapy using a palladium complex with zoledronic acid, the effect of tumor growth inhibition is accompanied by a change in its spectral characteristics. The parameters of the IR spectra for tumor tissue after treatment are close to those of the IR spectra for healthy tissue.

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

    PubMed Central

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

    2010-01-01

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

  16. The histological diagnosis of metastases to the breast from extramammary malignancies

    PubMed Central

    Lee, Andrew H S

    2007-01-01

    This study aims to review histological and immunohistochemical features that are useful in the diagnosis of metastases to the breast. Histological features were compared between non‐haematological metastases to the breast and 100 consecutive core biopsy specimens of primary invasive carcinomas of the breast. 18 non‐haematological metastases to the breast were diagnosed over a 10‐year period (0.3% of malignant mammary tumours). Elastosis and carcinoma in situ were seen only in primary mammary cancers. Two‐thirds of tumours had features raising the possibility of metastasis, such as clear cell carcinoma suggestive of renal origin and small cell carcinoma suggestive of pulmonary origin. The features observed in haematological metastases are also described. Immunohistochemical panels to distinguish mammary carcinoma (oestrogen receptor, gross cystic fluid protein‐15) from common metastases to the breast, including carcinoma of the lung (thyroid transcription factor‐1), malignant melanoma (S100, HMB45, melan‐A) and ovarian serous papillary carcinoma (Wilms' tumour 1), are discussed. The pathologist has a key role in considering the diagnosis of metastasis to the breast if the histological features are unusual for a primary mammary tumour. The clinical history is vital in some cases. Immunohistochemistry plays a useful supplementary role. PMID:18042689

  17. Involvement of EGFR in the promotion of malignant properties in multidrug resistant breast cancer cells.

    PubMed

    Xu, Jia-Wen; Li, Qing-Quan; Tao, Li-Li; Cheng, Yuan-Yuan; Yu, Juan; Chen, Qi; Liu, Xiu-Ping; Xu, Zu-De

    2011-12-01

    Multidrug resistance is the most predominant phenomenon leading to chemotherapy treatment failure in breast cancer patients. Despite many studies having suggested that overexpression of epidermal growth factor receptor (EGFR) is a potent predictor of malignancy in cancers, systematic research of EGFR in multidrug resistant (MDR) breast cancer cells is lacking. In order to clarify the role of EGFR in MDR breast cancer cells, MCF7/Adr expressing relatively higher EGFR, and its parental cell line MCF7 expressing relatively lower EGFR, were chosen for this study. Knockdown of EGFR by siRNA in MCF7/Adr cells showed that EGFR siRNA inhibits cell migration, invasion and proliferation in vitro; converse effects were observed in MCF7 cells transfected with pcDNA3.0-EGFR plasmid. Moreover, we found that EGFR upregulated migration and invasion via EMMPRIN, MMP2 and MMP9 in addition to promoting cell cycle passage via elevation of cyclin D1 and CDK4 in MDR breast cancer cells. Interestingly, MCF7/Adr cells not expressing EGFR showed significant decrease of P-glycoprotein (P-gp) and ABCG2 expression levels, and became more sensitive to treatment of adriamycin (ADR) and paclitaxel (Taxol); the above results indicated that MDR of cancer cells is related to S-phase arrest. In conclusion, EGFR is an important factor enhancing the malignancy of MDR breast cancer cells, partially, inducing MDR. Anti-EGFR therapy may improve outcome in chemorefractory breast cancer patients. PMID:21805028

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

    PubMed Central

    Danforth, David N.

    2016-01-01

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

  19. Tissue-Based Metabolomics to Analyze the Breast Cancer Metabolome.

    PubMed

    Budczies, Jan; Denkert, Carsten

    2016-01-01

    Mass spectrometry and nuclear magnetic resonance-based metabolomics have been developed into mature technologies that can be utilized to analyze hundreds of biological samples in a high-throughput manner. Over the past few years, both technologies were utilized to analyze large cohorts of fresh frozen breast cancer tissues. Metabolite biomarkers were shown to separate breast cancer tissues from normal breast tissues with high sensitivity and specificity. Furthermore, the metabolome differed between hormone receptor positive (HR+) and hormone receptor negative (HR-) breast cancer, but was unchanged in HER2+ tumors compared to HER2- tumors. New metabolism-related biomarkers were discovered including the 4-aminobutyrate aminotransferase ABAT, where low mRNA expression led to an accumulation of beta-alanine and shortened relapse-free survival. The glutamate-to-glutamine ratio (GGR) represents another new biomarker that was increased in 88 % of HR- tumors and 56 % of HR+ tumors compared to normal breast tissues. The GGR might help to stratify patients for the treatment with specific glutaminase inhibitors that were recently developed and are currently being tested in phase I clinical studies. Surprisingly, 2-hydroxyglutarate (2-HG), initially found to accumulate in isocitrate dehydrogenase (IDH) mutated gliomas and leukemias and described as an oncometabolite, was detected to be drastically increased in several breast carcinomas in the absence of IDH mutations. In summary, metabolomics analysis of breast cancer tissues is a reliable method and has produced many new biological insights that may impact breast cancer diagnostics and treatment over the coming years. PMID:27557538

  20. INDIVIDUALISED CALCULATION OF TISSUE IMPARTED ENERGY IN BREAST TOMOSYNTHESIS.

    PubMed

    Geeraert, N; Klausz, R; Muller, S; Bloch, I; Bosmans, H

    2016-06-01

    The imparted energy to the glandular tissue in the breast (glandular imparted energy, GIE) is proposed for an improved assessment of the individual radiation-induced risk resulting from X-ray breast imaging. GIE is computed from an estimation of the quantity and localisation of glandular tissue in the breast. After a digital breast tomosynthesis (DBT) acquisition, the volumetric glandular content (volumetric breast density, VBD) is computed from the central X-ray projection. The glandular tissue distribution is determined by labelling the DBT voxels to ensure the conservation of the VBD. Finally, the GIE is calculated by Monte Carlo computation on the resulting tissue-labelled DBT volume. For verification, the method was applied to 10 breast-shaped digital phantoms made of different glandular spheres in an adipose background, and to a digital anthropomorphic phantom. Results were compared to direct GIE computations on the phantoms considered as 'ground-truth'. The major limitations in accuracy are those of DBT, in particular the limited z-resolution. However, for most phantoms, the results can be considered as acceptable. PMID:27127209

  1. Nonlinear Elasto-Mammography for Characterization of Breast Tissue Properties

    PubMed Central

    Wang, Z. G.; Liu, Y.; Wang, G.; Sun, L. Z.

    2011-01-01

    Quantification of the mechanical behavior of normal and cancerous tissues has important implication in the diagnosis of breast tumor. The present work extends the authors' nonlinear elastography framework to incorporate the conventional X-ray mammography, where the projection of displacement information is acquired instead of full three-dimensional (3D) vector. The elastic parameters of normal and cancerous breast tissues are identified by minimizing the difference between the measurement and the corresponding computational prediction. An adjoint method is derived to calculate the gradient of the objective function. Simulations are conducted on a 3D breast phantom consisting of the fatty tissue, glandular tissue, and cancerous tumor, whose mechanical responses are hyperelastic in nature. The material parameters are identified with consideration of measurement error. The results demonstrate that the projective displacements acquired in X-ray mammography provide sufficient constitutive information of the tumor and prove the usability and robustness of the proposed method and algorithm. PMID:22235197

  2. Fatty Acid Composition of Tissue Cultured Breast Carcinoma and the Effect of Stearoyl-CoA Desaturase 1 Inhibition

    PubMed Central

    Mohammadzadeh, Fatemeh; Mosayebi, Gholamali; Montazeri, Vahid; Darabi, Maryam; Fayezi, Shabnam; Shaaker, Maghsod; Rahmati, Mohammad; Baradaran, Behzad; Mehdizadeh, Amir

    2014-01-01

    Purpose Stearoyl-CoA desaturase 1 (SCD1) is a novel therapeutic target in various malignancies, including breast cancer. The present study was designed to investigate the effect of the pharmacologic inhibition of SCD1 on fatty acid composition in tissue explant cultures of human breast cancer and to compare these effects with those in adjacent nonneoplastic breast tissue. Methods Paired samples of tumor and adjacent noncancerous tissue were isolated from 12 patients with infiltrating ductal breast cancer. Samples were explant cultured in vitro, exposed to the highly selective SCD1 inhibitor CAY10566, and examined for fatty acid composition by gas liquid chromatography. The cytotoxic and antigrowth effects were evaluated by quantification of lactate dehydrogenase release and by sulforhodamine B (SRB) measurement, respectively. Results Breast cancer tissue samples were found to have higher levels of monounsaturated fatty acids (MUFA) (p<0.001) and arachidonic acid (20:4n-6, p<0.001) and a lower level of linoleic acid (18:2n-6, p=0.02) than the normal-appearing breast tissues. While exhibiting no evident cytotoxicity, treatment with the SCD1 inhibitor, CAY10566 (0.1-1 µM), for 48 hours significantly increased 18:2n-6 levels in both the tumor and adjacent normal-appearing tissue (approximately 1.2 fold, p<0.05). However, the breast cancer tissue samples showed significant increases in the levels of MUFA and 20:4n-6 compared to the normal-appearing breast tissues (p<0.05). The SRB growth assay revealed a higher rate of inhibition with the SCD1 inhibitor in breast cancer tissues than in normal-appearing tissues (p<0.01, 41% vs. 29%). The SCD1 inhibitor also elevated saturated fatty acid (1.46-fold, p=0.001) levels only in the tumor tissue explant. Conclusion The fatty acid composition and response to SCD1 inhibition differed between the explant cultures from breast cancer and the adjacent normal-appearing tissue. Altered fatty acid composition induced by SCD1 inhibition

  3. MiR-300 regulate the malignancy of breast cancer by targeting p53

    PubMed Central

    Xu, Xiao-Heng; Li, Da-Wei; Feng, Hui; Chen, Hong-Mei; Song, Yan-Qiu

    2015-01-01

    Objective: In this study, we investigated the role of miR-300 in regulating cell proliferation and invasion of breast cancer (BC) cells. Methods: MicroRNA and protein expression patterns were compared between breast cancer tissue and normal tissue and between two different prognostic groups. The up-regulation of miR-300 was confirmed by real-time reverse transcription polymerase chain reaction and its expression was analyzed in MCF-7 breast cancer cells. Results: We observed that miR-300 expression was frequently and dramatically up-regulated in human breast cancer tissues and cell lines compared with the matched adjacent normal tissues and cells. We further showed that transient and stable over-expression of miR-300 could promote cell proliferation and cell cycle progression. Moreover, p53, a key inhibitor of cell cycle, was verified as a direct target of miR-300, suggesting that miR-300 might promote breast cancer cell proliferation and invasion by regulating p53 expression. Conclusion: Our findings indicated that miR-300 up-regulation might exert some sort of antagonistic function by targeting p53 in breast cancer cell proliferation during breast tumorigenesis. PMID:26221232

  4. Bimodal Multiparameter-Based Approach for Benign-Malignant Classification of Breast Tumors.

    PubMed

    Ara, Sharmin R; Alam, Farzana; Rahman, Md Hadiur; Akhter, Shabnam; Awwal, Rayhana; Hasan, Kamrul

    2015-07-01

    Proposed here is a breast tumor classification technique using conventional ultrasound B-mode imaging and a new elasticity imaging-based bimodal multiparameter index. A set of conventional ultrasound (US) and ultrasound elastography (UE) parameters are studied, and among those, the effective ones whose independent as well as combined performance is found satisfactory are selected. To improve the combined US performance, two new US parameters are proposed: edge diffusivity, which assesses edge blurriness to differentiate malignant from benign lesions, and the shape asymmetry factor, which quantifies tumor shape irregularity by comparing the tumor boundary with an ellipse fitted to the lesion. Then a new bimodal multiparameter characterization index is defined to discriminate 201 pathologically confirmed breast tumors of which 56 are malignant lesions, 79 are fibroadenomas, 42 are cysts and 24 are inflammatory lesions. The weights of the multiparameter bimodal index are optimally computed using a genetic algorithm (GA). To evaluate the performance variation of the index on different data sets, the tumors are categorized into three classes: malignant lesion versus fibroadenoma, malignant lesion versus fibroadenoma and cyst and malignant lesion versus fibroadenoma, cyst and inflammation. The test results reveal that the proposed bimodal index achieves satisfactory quality metrics (e.g., 94.64%-98.21% sensitivity, 97.24%-100.00% specificity and 96.52%-99.44% accuracy) for classification of the aforementioned three classes of breast tumors. Its performance is also observed to be better in totality of the quality metrics sensitivity, specificity, accuracy, positive predictive value and negative predictive value as compared with that of a conventional bimodal index as well as unimodal multiparameter indices based on US or UE. It is suggested that the proposed simple bimodal linear classifier may assist radiologists in better diagnosis of breast tumors and help reduce the

  5. The Lipid Phenotype of Breast Cancer Cells Characterized by Raman Microspectroscopy: Towards a Stratification of Malignancy

    PubMed Central

    Santana-Codina, Naiara; Rao, Satish; Petrov, Dmitri; Sierra, Angels

    2012-01-01

    Although molecular classification brings interesting insights into breast cancer taxonomy, its implementation in daily clinical care is questionable because of its expense and the information supplied in a single sample allocation is not sufficiently reliable. New approaches, based on a panel of small molecules derived from the global or targeted analysis of metabolic profiles of cells, have found a correlation between activation of de novo lipogenesis and poorer prognosis and shorter disease-free survival for many tumors. We hypothesized that the lipid content of breast cancer cells might be a useful indirect measure of a variety of functions coupled to breast cancer progression. Raman microspectroscopy was used to characterize metabolism of breast cancer cells with different degrees of malignancy. Raman spectra from MDA-MB-435, MDA-MB-468, MDA-MB-231, SKBR3, MCF7 and MCF10A cells were acquired with an InVia Raman microscope (Renishaw) with a backscattered configuration. We used Principal Component Analysis and Partial Least Squares Discriminant Analyses to assess the different profiling of the lipid composition of breast cancer cells. Characteristic bands related to lipid content were found at 3014, 2935, 2890 and 2845 cm−1, and related to lipid and protein content at 2940 cm−1. A classificatory model was generated which segregated metastatic cells and non-metastatic cells without basal-like phenotype with a sensitivity of 90% and a specificity of 82.1%. Moreover, expression of SREBP-1c and ABCA1 genes validated the assignation of the lipid phenotype of breast cancer cells. Indeed, changes in fatty acid unsaturation were related with the epithelial-to-mesenchymal transition phenotype. Raman microspectroscopy is a promising technique for characterizing and classifying the malignant phenotype of breast cancer cells on the basis of their lipid profiling. The algorithm for the discrimination of metastatic ability is a first step towards stratifying breast cancer

  6. Concentrations of cadmium and selected essential elements in malignant large intestine tissue

    PubMed Central

    Dziki, Adam; Kilanowicz, Anna; Sapota, Andrzej; Duda-Szymańska, Joanna; Daragó, Adam

    2015-01-01

    Introduction Colorectal cancer is one of the most common cancers worldwide. Incidence rates of large intestine cancer indicate a role of environmental and occupational factors. The role of essential elements and their interaction with toxic metals can contribute to the explanation of a complex mechanism by which large intestine cancer develops. Bearing this in mind, determining the levels of essential and toxic elements in tissues (organs), as well as in body fluids, seems to shed light on their role in the mode of action in malignant disease. Aim Determination of the levels of cadmium, zinc, copper, selenium, calcium, magnesium, and iron in large intestine malignant tissue. Material and methods Two intraoperative intestine sections were investigated: one from the malignant tissue and the other one from the normal tissue, collected from each person with diagnosed large intestine cancer. Cadmium, zinc, copper, calcium, magnesium, and iron levels were determined with atomic absorption spectrometry, and selenium levels by spectrofluorimetric method. Results The levels of copper, selenium, and magnesium were higher in the malignant than in normal tissues. In addition, the zinc/copper and calcium/magnesium relationship was altered in malignant tissue, where correlations were lower compared to non-malignant tissue. Conclusions The results seems to demonstrate disturbed homeostasis of some essential elements. However, it is hard to confirm their involvement in the aetiology of colorectal cancer. PMID:27110307

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

    PubMed

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

    2010-11-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  9. Aromatase Expression Increases the Survival and Malignancy of Estrogen Receptor Positive Breast Cancer Cells

    PubMed Central

    Bandyopadhyay, Abhik; Kirma, Nameer B.; Tekmal, Rajeshwar R.; Wang, Shui; Sun, Lu-Zhe

    2015-01-01

    In postmenopausal women, local estrogen produced by adipose stromal cells in the breast is believed to support estrogen receptor alpha (ERα) positive breast cancer cell survival and growth. This raises the question of how the ERα positive metastatic breast cancer cells survive after they enter blood and lymph circulation, where estrogen level is very low in postmenopausal women. In this study, we show that the aromatase expression increased when ERα positive breast cancer cells were cultured in suspension. Furthermore, treatment with the aromatase substrate, testosterone, inhibited suspension culture-induced apoptosis whereas an aromatase inhibitor attenuated the effect of testosterone suggesting that suspended circulating ERα positive breast cancer cells may up-regulate intracrine estrogen activity for survival. Consistent with this notion, a moderate level of ectopic aromatase expression rendered a non-tumorigenic ERα positive breast cancer cell line not only tumorigenic but also metastatic in female nude mice without exogenous estrogen supplementation. The increased malignant phenotype was confirmed to be due to aromatase expression as the growth of orthotopic tumors regressed with systemic administration of an aromatase inhibitor. Thus, our study provides experimental evidence that aromatase plays an important role in the survival of metastatic ERα breast cancer cells by suppressing anoikis. PMID:25837259

  10. Case report of concurrent primary malignancies of the breast and nasopharynx

    PubMed Central

    PAN, XINBIN; ZHU, XIAODONG; LI, QINGDI QUENTIN

    2012-01-01

    The aim of this study was to report a case of concurrent primary malignancies of the breast and nasopharynx and discuss the potential relationship between Epstein-Barr virus (EBV) infection and breast cancer. A 39-year-old female presented with a palpable mass present for 1 year in her left breast. Immunohistochemical staining was performed and the results showed that the tumor cells were immunopositive for the estrogen receptor, progesterone receptor and p53 protein, and markedly positive for C-erb B2. In addition, 30% of the tumor cells were positive for the Ki-67 antigen. Blood test results revealed that EBV-CA-IgG was present and EBV-EA-IgG was reactivated. The patient was diagnosed with breast cancer (T1N0M0) and EBV infection. A mastectomy with axillary clearance was performed on the left breast. Histopathological examination provided evidence of invasive ductal adenocarcinoma. Further evaluation due to epistaxis following the breast surgery resulted in a diagnosis of nasopharyngeal carcinoma (T2N1M0). Histopathology showed a non-keratinizing undifferentiated carcinoma. The patient was treated with chemoradiotherapy for nasopharyngeal carcinoma. Twelve months following surgery and chemoradiotherapy the patient was assessed at the Cancer Hospital of Guangxi Medical University outpatient clinic and no evidence of relapse or metastasis was found. Thus, EBV infection may be involved in the pathogenesis of breast cancer, as observed in nasopharyngeal carcinoma. PMID:22844371

  11. Malignant phyllodes tumor of the breast presenting with hypoglycemia: a case report and literature review

    PubMed Central

    Pacioles, Toni; Seth, Rahul; Orellana, Cesar; John, Ivy; Panuganty, Veera; Dhaliwal, Ruban

    2014-01-01

    Phyllodes tumors are rare fibroepithelial neoplasms that account for less than 1% of all breast tumors and are typically found in middle-aged women. Phyllodes tumors that present with hypoglycemia are even rarer. No one morphologic finding is reliable in predicting the clinical behavior of this tumor. Surgery has been the primary mode of treatment to date. However, the extent of resection and the role of adjuvant radiotherapy or chemotherapy are still controversial. Here, we present a challenging case of malignant phyllodes tumor of the breast associated with hypoglycemia, and review the literature regarding clinical findings, pathologic risk factors for recurrence, and treatment recommendations. PMID:25525388

  12. Bovine Leukemia Virus DNA in Human Breast Tissue

    PubMed Central

    Shen, Hua Min; Jensen, Hanne M.; Choi, K. Yeon; Sun, Dejun; Nuovo, Gerard

    2014-01-01

    Bovine leukemia virus (BLV), a deltaretrovirus, causes B-cell leukemia/lymphoma in cattle and is prevalent in herds globally. A previous finding of antibodies against BLV in humans led us to examine the possibility of human infection with BLV. We focused on breast tissue because, in cattle, BLV DNA and protein have been found to be more abundant in mammary epithelium than in lymphocytes. In human breast tissue specimens, we identified BLV DNA by using nested liquid-phase PCR and DNA sequencing. Variations from the bovine reference sequence were infrequent and limited to base substitutions. In situ PCR and immunohistochemical testing localized BLV to the secretory epithelium of the breast. Our finding of BLV in human tissues indicates a risk for the acquisition and proliferation of this virus in humans. Further research is needed to determine whether BLV may play a direct role in human disease. PMID:24750974

  13. Effect of polyclonal activators on cytokine production by blood cells and by malignant breast cancer cells.

    PubMed

    Kunts, T A; Karpukhina, K V; Mikhaylova, E S; Marinkin, I O; Varaksin, N A; Autenshlyus, A I; Lyakhovich, V V

    2016-01-01

    The production of cytokines by peripheral blood cells and biopsy specimens of tumors stimulated by polyclonal activators (PAs) was evaluated in 34 patients with invasive ductal breast carcinoma using enzyme-linked immunosorbent assay (ELISA). Positive correlation between the stimulation index of polyclonal activators (SIPA) for IL-18 production by the tumor and the relative content of poorly differentiated cells was revealed. The latter, in turn, was positively correlated with the numbers of normal and pathologic mitoses and the degree of malignancy. Cancer cells can produce IL-18, which is involved in the process of angiogenesis, stimulates invasion and metastasis. Decrease in SIPA for the production of IL-6 and GCSF by peripheral blood cells could serve as an indicator of malignant progression in invasive ductal breast carcinoma. PMID:27021370

  14. Metastatic tumor of the hand from malignant cystosarcoma phylloides of the breast. A case report.

    PubMed

    Patel, M R; Anand, V S; Desai, S S

    1985-03-01

    In this case report, a malignant cystosarcoma phylloides of the breast metastasized to the pulp of the little finger in a 47-year-old woman. It initially masqueraded as a whitlow. The diagnosis was helped by radionuclide bone scanning, which showed multiple areas of increased focal uptake including the terminal phalanx of the fifth finger, and the diagnosis was established by a frozen section biopsy of the tumor. The patient underwent a palliative fifth ray resection. She died within six weeks of surgery from extensive pulmonary and osseous metastases. Review of literature revealed only one other case of malignant cystosarcoma phylloides of the breast that metastasized to the hand and was initially misdiagnosed as a whitlow. PMID:3006003

  15. Raman spectrosopic characterization of human malignant tissues: implications for a percutaneous optical biopsy technique for in-situ tissue diagnosis

    NASA Astrophysics Data System (ADS)

    Redd, Douglas C. B.; Frank, Christopher J.; Feng, Zhe Chuan; Gansler, Ted S.; McCreery, Richard L.

    1994-01-01

    Recent advancements in the technique of Raman spectroscopy now make it possible to achieve rapid, minimally invasive and non-destructive characterization of tissues. In order to evaluate the efficacy of this technique for diagnosis, the Raman spectra of normal and neoplastic human tissues (e.g., breast, kidney, liver and colon) were obtained utilizing visible and near-IR excitation. Normal breast tissue and colon adenocarcinoma showed major Raman features due to the presence of carotenoids and lipids. In breast carcinoma, the features due to lipids were attenuated and as fibrosis (desmoplasia) increased, new spectral features attributable to collagen were observed. Samples of normal and neoplastic liver and kidney show unique spectral differences sufficient to permit tissue differentiation.

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

    SciTech Connect

    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.

  17. Superoxide anion and proteasomal dysfunction contribute to curcumin-induced paraptosis of malignant breast cancer cells.

    PubMed

    Yoon, Mi Jin; Kim, Eun Hee; Lim, Jun Hee; Kwon, Taeg Kyu; Choi, Kyeong Sook

    2010-03-01

    Curcumin is considered a pharmacologically safe agent that may be useful in cancer chemoprevention and therapy. Here, we show for the first time that curcumin effectively induces paraptosis in malignant breast cancer cell lines, including MDA-MB-435S, MDA-MB-231, and Hs578T cells, by promoting vacuolation that results from swelling and fusion of mitochondria and/or the endoplasmic reticulum (ER). Inhibition of protein synthesis by cycloheximide blocked curcumin-induced vacuolation and subsequent cell death, indicating that protein synthesis is required for this process. The levels of AIP-1/Alix protein, a known inhibitor protein of paraptosis, were progressively downregulated in curcumin-treated malignant breast cancer cells, and AIP-1/Alix overexpression attenuated curcumin-induced death in these cells. ERK2 and JNK activation were positively associated with curcumin-induced cell death. Mitochondrial superoxide was shown to act as a critical early signal in curcumin-induced paraptosis, whereas proteasomal dysfunction was mainly responsible for the paraptotic changes associated with ER dilation. Notably, curcumin-induced paraptotic events were not observed in normal breast cells, including mammary epithelial cells and MCF-10A cells. Taken together, our findings on curcumin-induced paraptosis may provide novel insights into the mechanisms underlying the selective anti-cancer effects of curcumin against malignant cancer cells. PMID:20036734

  18. RELATIONSHIP OF MAMMOGRAPHIC DENSITY AND GENE EXPRESSION: ANALYSIS OF NORMAL BREAST TISSUE SURROUNDING BREAST CANCER

    PubMed Central

    Sandhu, Rupninder; Williams, Tyisha; Midkiff, Bentley R.; Lissowska, Jolanta; Wesolowska, Ewa; Boyd, Norman F.; Johnson, Nicole B.; Figueroa, Jonine D.; Sherman, Mark E.; Troester, Melissa A.

    2014-01-01

    Purpose Previous studies of breast tissue gene expression have demonstrated that the extratumoral microenvironment has substantial variability across individuals, some of which can be attributed to epidemiologic factors. To evaluate how mammographic density (MD) and breast tissue composition relate to extratumoral microenvironment gene expression, we used data on 121 breast cancer patients from the population-based Polish Women's Breast Cancer Study. Design Breast cancer cases were classified based on a previously reported, biologically-defined extratumoral gene expression signature with two subtypes: an Active subtype, which is associated with high expression of genes related to fibrosis and wound response, and an Inactive subtype, which has high expression of cellular adhesion genes. MD of the contralateral breast was assessed using pre-treatment mammograms and a quantitative, reliable computer-assisted thresholding method. Breast tissue composition was evaluated based on digital image analysis of tissue sections. Results The Inactive extratumoral subtype was associated with significantly higher percentage mammographic density (PD) and dense area (DA) in univariate analysis (PD: p=0.001; DA: p=0.049) and in multivariable analyses adjusted for age and body mass index (PD: p=0.004; DA: p=0.049). Inactive/higher MD tissue was characterized by a significantly higher percentage of stroma and a significantly lower percentage of adipose tissue, with no significant change in epithelial content. Analysis of published gene expression signatures suggested that Inactive/higher MD tissue expressed increased estrogen response and decreased TGF-β signaling. Conclusions By linking novel molecular phenotypes with MD, our results indicate that MD reflects broad transcriptional changes, including changes in both epithelia- and stroma-derived signaling. PMID:23918601

  19. Improved Characterization of Healthy and Malignant Tissue by NMR Line-Shape Relaxation Correlations

    PubMed Central

    Peemoeller, H.; Shenoy, R.K.; Pintar, M.M.; Kydon, D.W.; Inch, W.R.

    1982-01-01

    We performed a relaxation-line-shape correlation NMR experiment on muscle, liver, kidney, and spleen tissues of healthy mice and of mouse tumor tissue. In each tissue studied, five spin groups were resolved and characterized by their relaxation parameters. We report a previously uncharacterized semi-solid spin group and discuss briefly the value of this method for the identification of malignant tissues. PMID:7104438

  20. Disposition of hop prenylflavonoids in human breast tissue

    PubMed Central

    Bolca, Selin; Li, Jinghu; Nikolic, Dejan; Roche, Nathalie; Blondeel, Phillip; Possemiers, Sam; De Keukeleire, Denis; Bracke, Marc; Heyerick, Arne; van Breemen, Richard B.; Depypere, Herman

    2013-01-01

    Hop-derived products may contain xanthohumol (XN), isoxanthohumol (IX), and the potent phytoestrogen 8-prenylnaringenin (8-PN). To evaluate the potential health effects of these prenylflavonoids on breast tissue, their concentration, nature of metabolites, and biodistribution were assessed and compared to 17β-estradiol (E2) exposure. In this dietary intervention study, women were randomly allocated to hop (n=11; 2.04 mg XN, 1.20 mg IX, and 0.1 mg 8-PN per supplement) or control (n=10). After a run-in of ≥4d, 3 supplements were taken daily during 5d preceding an aesthetic breast reduction. Blood and breast biopsies were analyzed using HPLC-ESI-MS/MS. Upon hop administration, XN and IX concentrations ranged between 0.72–17.65 nmol/L and 3.30–31.50 nmol/L, and between 0.26– 5.14 pmol/g and 1.16–83.67 pmol/g in hydrolyzed serum and breast tissue, respectively. 8-PN however, was only detected in samples of moderate and strong 8-PN producers (0.43–7.06 nmol/L and 0.78–4.83 pmol/g). Phase I metabolism appeared to be minor (~10%), whereas extensive glucuronidation was observed (>90%). Total prenylflavonoids showed a breast adipose/glandular tissue distribution of 38/62 and their derived E2-equivalents were negligible compared to E2 in adipose (384.6±118.8 fmol/g, P=0.009) and glandular (241.6±93.1 fmol/g, P<0.001) tissue, respectively. Consequently, low doses of prenylflavonoids are unlikely to elicit estrogenic responses in breast tissue. PMID:20486208

  1. Disposition of hop prenylflavonoids in human breast tissue.

    PubMed

    Bolca, Selin; Li, Jinghu; Nikolic, Dejan; Roche, Nathalie; Blondeel, Phillip; Possemiers, Sam; De Keukeleire, Denis; Bracke, Marc; Heyerick, Arne; van Breemen, Richard B; Depypere, Herman

    2010-07-01

    Hop-derived products may contain xanthohumol (XN), isoxanthohumol (IX), and the potent phytoestrogen 8-prenylnaringenin (8-PN). To evaluate the potential health effects of these prenylflavonoids on breast tissue, their concentration, nature of metabolites, and biodistribution were assessed and compared with 17beta-estradiol (E(2)) exposure. In this dietary intervention study, women were randomly allocated to hop (n=11; 2.04 mg XN, 1.20 mg IX, and 0.1 mg 8-PN per supplement) or control (n=10). After a run-in of >or=4 days, three supplements were taken daily for 5 days preceding an aesthetic breast reduction. Blood and breast biopsies were analyzed using HPLC-ESI-MS/MS. Upon hop administration, XN and IX concentrations ranged between 0.72 and 17.65 nmol/L and 3.30 and 31.50 nmol/L, and between 0.26 and 5.14 pmol/g and 1.16 and 83.67 pmol/g in hydrolyzed serum and breast tissue, respectively. 8-PN however, was only detected in samples of moderate and strong 8-PN producers (0.43-7.06 nmol/L and 0.78-4.83 pmol/g). Phase I metabolism appeared to be minor (approximately 10%), whereas extensive glucuronidation was observed (> 90%). Total prenylflavonoids showed a breast adipose/glandular tissue distribution of 38/62 and their derived E(2)-equivalents were negligible compared with E(2) in adipose (384.6+/-118.8 fmol/g, p=0.009) and glandular (241.6+/-93.1 fmol/g, p<0.001) tissue, respectively. Consequently, low doses of prenylflavonoids are unlikely to elicit estrogenic responses in breast tissue. PMID:20486208

  2. Antibiotic residues distribute uniformly in broiler chicken breast muscle tissue.

    PubMed

    Reyes-Herrera, Ixchel; Donoghue, Dan J

    2008-01-01

    Use of antibiotics by the poultry industry has the potential to produce residues in edible tissues. In order to protect consumers, the U.S. federal government performs extensive evaluations to quantify residues in edible tissues to ensure that concentrations do not exceed the tolerance level. However, in the case of muscle tissue, the regulatory process does not differentiate between different edible muscle types in poultry. Previous studies performed by our laboratory determined higher fluoroquinolone residue concentrations in breast versus thigh muscle. Thus, if thigh tissues were used for residue monitoring, it would not accurately depict the higher concentrations. It is also possible that residue concentrations vary within tissues. To evaluate this possibility, fluoroquinolone antibiotic residues were determined for different breast sections. One hundred sixty chickens were randomly divided into four groups and dosed at 33 days of age with the fluoroquinolone antibiotic, enrofloxacin (Baytril), at either 25 ppm for 3 days, 25 ppm for 7 days, 50 ppm for 3 days, or 50 ppm for 7 days. Breast fillets were collected from each bird (n = 5 birds per day per group) during the dosing and withdrawal period. Each breast was divided into four sections (upper left, upper right, lower left, and lower right) that were analyzed as individual samples for determination of fluoroquinolone concentration. Our results indicated no significant difference (P > 0.05) in the levels of enrofloxacin residues between breast sections during the dosing or withdrawal periods. Consequently, samples can be collected from any breast section to evaluate fluoroquinolone residue concentrations during the regulatory monitoring process. PMID:18236689

  3. Endometriosis, in vitro fertilisation and the risk of gynaecological malignancies, including ovarian and breast cancer.

    PubMed

    Vlahos, Nikos F; Economopoulos, Konstantinos P; Fotiou, Stylianos

    2010-02-01

    There is evidence that endometriosis as well as drugs used in the process of in vitro fertilisation appear to associate with increased risk for gynaecological cancer. In this review, we attempt to describe this relationship according to the most recent epidemiologic data and to present the possible mechanisms on the molecular level that could potentially explain this correlation. There are data to support that ovarian endometriosis could have the potential for malignant transformation. Epidemiologic and genetic studies support this notion. It seems that endometriosis is associated with specific types of ovarian cancer (endometrioid and clear cell). There is no clear association between endometriosis and breast or endometrial cancer. More studies are needed to establish the risk factors that may lead to malignant transformation of this condition and to identify predisposed individuals who may require closer surveillance. Currently, there is no proven relationship between any type of gynaecological cancer and drugs used for infertility treatment. In principle, infertile women have increased risk for gynaecologic malignancies. Nulligravidas who received treatment are at increased risk for malignancy compared with women who had conceived after treatment. There is limited evidence that clomiphene citrate use for more than six cycles or 900mg or treatment of women over the age of 40 could increase their risk for ovarian and breast cancer. More studies with the appropriate statistical power and follow-up time are required to evaluate accurately the long-term effects of these drugs and procedures. PMID:19733123

  4. Classification of benign and malignant breast masses based on shape and texture features in sonography images.

    PubMed

    Zakeri, Fahimeh Sadat; Behnam, Hamid; Ahmadinejad, Nasrin

    2012-06-01

    The purpose of this research was evaluating novel shape and texture feature' efficiency in classification of benign and malignant breast masses in sonography images. First, mass regions were extracted from the region of interest (ROI) sub-image by implementing a new hybrid segmentation approach based on level set algorithms. Then two left and right side areas of the masses are elicited. After that, six features (Eccentricity_feature, Solidity_feature, DeferenceArea_Hull_Rectangular, DeferenceArea_Mass_Rectangular, Cross-correlation-left and Cross-correlation-right) based on shape, texture and region characteristics of the masses were extracted for further classification. Finally a support vector machine (SVM) classifier was utilized to classify breast masses. The leave-one-case-out protocol was utilized on a database of eighty pathologically-proven breast sonographic images of patients (forty-seven benign cases and thirty-three malignant cases) to evaluate our method. The classification results showed an overall accuracy of 95.00%, sensitivity of 90.91%, specificity of 97.87%, positive predictive value of 96.77%, negative predictive value of 93.88%, and Matthew's correlation coefficient of 89.71%. The experimental results declare that our proposed method is actually a beneficial tool for the diagnosis of the breast cancer and can provide a second opinion for a physician's decision or can be used for the medicine training especially when coupled with other modalities. PMID:21082222

  5. High-resolution diffusion-weighted imaging for the separation of benign from malignant BI-RADS 4/5 lesions found on breast MRI at 3 Tesla

    PubMed Central

    Wisner, Dorota J.; Rogers, Nathan; Deshpande, Vibhas S.; Newitt, David N.; Laub, Gerhard A.; Porter, David A.; Kornak, John; Joe, Bonnie N.; Hylton, Nola M.

    2013-01-01

    Purpose To determine whether readout-segmented echo-planar diffusion imaging (RESOLVE) improves separation of malignant versus benign lesions compared to standard single-shot echo-planar imaging (ss-EPI) on BI-RADS 4/5 lesions detected on breast MRI. Materials and Methods Consecutive 3T breast MRI studies with BI-RADS 4/5 designation and subsequent biopsy or benign mastectomy were retrospectively identified. Freehand ROI’s were drawn on lesions and also on normal background fibroglandular tissue for comparison. Lesion-to-background contrast was evaluated by normalizing signal intensity of the lesion ROI by the normal background tissue ROI at b=800. Statistical analysis used the Mann-Whitney/Wilcoxon rank-sum test for unpaired and Wilcoxon signed-rank for paired comparisons. Results Of 38 lesions in 32 patients,10 were malignant. Lesion-to-background contrast was higher on RESOLVE than ss-EPI (1.80±0.71 vs. 1.62±0.63, p=0.03). Mean ADC was the same or lower on RESOLVE than ss-EPI, and this effect was largest in malignant lesions (RESOLVE 0.90±0.13; ss-EPI 1.00±0.13; median difference −0.10 (95%CI: −0.17,−0.02) ×10−3mm2/sec; p=0.014). By either diffusion method, there was a statistically significant difference between benign and malignant mean ADC (p<0.001). Conclusion Increased lesion-to-background contrast and improved separation of benign from malignant lesions by RESOLVE compared to standard diffusion, suggest that RESOLVE may show promise as an adjunct to clinical breast MRI. PMID:24214467

  6. Diffraction tomography applied to simulated ultrasound through breast tissue

    NASA Astrophysics Data System (ADS)

    Chambers, David H.

    2002-11-01

    Diffraction tomography is used to obtain images of sound speed and attenuation of a slice of breast tissue obtained from the Visible Woman data set. Simulated ultrasound data was generated using an acoustic propagation code run on the ASCI Blue Pacific computer at Lawrence Livermore National Laboratory. Data was generated for a slice of healthy tissue, and a slice with simulated lesions to determine the ability of the imaging method to detect various abnormalities in the breast. In addition, the time reversal operator for the slice was constructed from the data and the eigenfunctions backpropagated into the slice as first suggested by Mast [Mast, Nachman, and Waag, J. Acoust. Soc. Am. 102(2)] to identify structures associated with each time reversal mode for both the healthy tissue and tissue with lesions.

  7. Metachronous Occurrence of Granular Cell Tumor in Breast Skin and Scalp: Diagnostic Challenging Differentiating Benign from Malignant and a Literature Review.

    PubMed

    Akkaya, Hampar; Toru, Havva Serap; Ayva, Ebru Sebnem; Karabulut, Zulfikar; Durusoy, Cicek

    2016-01-01

    Granular cell tumor (GCT) is a Schwann cell related benign neoplasm of soft tissue. GCT is an uncommon entity that occurs in a wide variety of body sites, but it is generally presented in the skin, oral cavity, superficial soft tissue, and respiratory and digestive tracts. Most of the GCTs are benign but clinically and radiologically these may mimic malignancy. Histopathological diagnosis is gold standard for establishing the true nature of the lesion. GCT is most commonly solitary but in about 10% of cases can be multifocal, usually involving various skin and soft tissue sites versus involving various internal sites. Therefore, these can involve skin and soft tissue or submucosa and viscera. GCT is usually benign; however, local recurrence is common due to incomplete removal. Malignant cases are rarely reported in 1-2% of cases. In this study, we report clinical and histopathological findings of a 36-year-old woman with metachronous GCT in breast and scalp. The clinical features raise the question of whether these are metachronous benign GCTs or whether this is establishment of malignant behavior. The aim of this report is to present the histopathological and clinical features of GCT and the diagnostic challenge of differentiating benign from malignant GCT. PMID:26881167

  8. Simultaneous mitochondrial Ca(2+) overload and proteasomal inhibition are responsible for the induction of paraptosis in malignant breast cancer cells.

    PubMed

    Yoon, Mi Jin; Kim, Eun Hee; Kwon, Taeg Kyu; Park, Sun Ah; Choi, Kyeong Sook

    2012-11-28

    In this study, we investigated the role of Ca(2+) in curcumin-induced paraptosis, a cell death mode that is accompanied by dilation of mitochondria and the endoplasmic reticulum (ER). Curcumin induced mitochondrial Ca(2+) overload selectively in the malignant breast cancer cells, but not in the normal breast cell, contributing to the dilation of mitochondria/ER and subsequent paraptotic cell death. In addition, we found that simultaneous inhibition of the mitochondrial Na(+)/Ca(2+) exchanger (mNCX) and proteasomes can trigger a sustained mitochondrial Ca(2+) overload and effectively induce paraptosis in malignant breast cancer cells. PMID:22634500

  9. Surface-enhanced Raman spectroscopy of saliva proteins for the noninvasive differentiation of benign and malignant breast tumors

    PubMed Central

    Feng, Shangyuan; Huang, Shaohua; Lin, Duo; Chen, Guannan; Xu, Yuanji; Li, Yongzeng; Huang, Zufang; Pan, Jianji; Chen, Rong; Zeng, Haishan

    2015-01-01

    The capability of saliva protein analysis, based on membrane protein purification and surface-enhanced Raman spectroscopy (SERS), for detecting benign and malignant breast tumors is presented in this paper. A total of 97 SERS spectra from purified saliva proteins were acquired from samples obtained from three groups: 33 healthy subjects; 33 patients with benign breast tumors; and 31 patients with malignant breast tumors. Subtle but discernible changes in the mean SERS spectra of the three groups were observed. Tentative assignments of the saliva protein SERS spectra demonstrated that benign and malignant breast tumors led to several specific biomolecular changes of the saliva proteins. Multiclass partial least squares–discriminant analysis was utilized to analyze and classify the saliva protein SERS spectra from healthy subjects, benign breast tumor patients, and malignant breast tumor patients, yielding diagnostic sensitivities of 75.75%, 72.73%, and 74.19%, as well as specificities of 93.75%, 81.25%, and 86.36%, respectively. The results from this exploratory work demonstrate that saliva protein SERS analysis combined with partial least squares–discriminant analysis diagnostic algorithms has great potential for the noninvasive and label-free detection of breast cancer. PMID:25609959

  10. Breast tissue decomposition with spectral distortion correction: A postmortem study

    PubMed Central

    Ding, Huanjun; Zhao, Bo; Baturin, Pavlo; Behroozi, Farnaz; Molloi, Sabee

    2014-01-01

    Purpose: To investigate the feasibility of an accurate measurement of water, lipid, and protein composition of breast tissue using a photon-counting spectral computed tomography (CT) with spectral distortion corrections. Methods: Thirty-eight postmortem breasts were imaged with a cadmium-zinc-telluride-based photon-counting spectral CT system at 100 kV. The energy-resolving capability of the photon-counting detector was used to separate photons into low and high energy bins with a splitting energy of 42 keV. The estimated mean glandular dose for each breast ranged from 1.8 to 2.2 mGy. Two spectral distortion correction techniques were implemented, respectively, on the raw images to correct the nonlinear detector response due to pulse pileup and charge-sharing artifacts. Dual energy decomposition was then used to characterize each breast in terms of water, lipid, and protein content. In the meantime, the breasts were chemically decomposed into their respective water, lipid, and protein components to provide a gold standard for comparison with dual energy decomposition results. Results: The accuracy of the tissue compositional measurement with spectral CT was determined by comparing to the reference standard from chemical analysis. The averaged root-mean-square error in percentage composition was reduced from 15.5% to 2.8% after spectral distortion corrections. Conclusions: The results indicate that spectral CT can be used to quantify the water, lipid, and protein content in breast tissue. The accuracy of the compositional analysis depends on the applied spectral distortion correction technique. PMID:25281953

  11. Breast tissue decomposition with spectral distortion correction: A postmortem study

    SciTech Connect

    Ding, Huanjun; Zhao, Bo; Baturin, Pavlo; Behroozi, Farnaz; Molloi, Sabee

    2014-10-15

    Purpose: To investigate the feasibility of an accurate measurement of water, lipid, and protein composition of breast tissue using a photon-counting spectral computed tomography (CT) with spectral distortion corrections. Methods: Thirty-eight postmortem breasts were imaged with a cadmium-zinc-telluride-based photon-counting spectral CT system at 100 kV. The energy-resolving capability of the photon-counting detector was used to separate photons into low and high energy bins with a splitting energy of 42 keV. The estimated mean glandular dose for each breast ranged from 1.8 to 2.2 mGy. Two spectral distortion correction techniques were implemented, respectively, on the raw images to correct the nonlinear detector response due to pulse pileup and charge-sharing artifacts. Dual energy decomposition was then used to characterize each breast in terms of water, lipid, and protein content. In the meantime, the breasts were chemically decomposed into their respective water, lipid, and protein components to provide a gold standard for comparison with dual energy decomposition results. Results: The accuracy of the tissue compositional measurement with spectral CT was determined by comparing to the reference standard from chemical analysis. The averaged root-mean-square error in percentage composition was reduced from 15.5% to 2.8% after spectral distortion corrections. Conclusions: The results indicate that spectral CT can be used to quantify the water, lipid, and protein content in breast tissue. The accuracy of the compositional analysis depends on the applied spectral distortion correction technique.

  12. Differentiating cancerous from normal breast tissue by redox imaging

    NASA Astrophysics Data System (ADS)

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

    2015-02-01

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

  13. Optical breast cancer margin assessment: an observational study of the effects of tissue heterogeneity on optical contrast

    PubMed Central

    2010-01-01

    Introduction Residual cancer following breast conserving surgery increases the risk of local recurrence and mortality. Margin assessment presents an unmet clinical need. Breast tissue is markedly heterogeneous, which makes distinguishing small foci of cancer within the spectrum of normal tissue potentially challenging. This is further complicated by the heterogeneity as a function of menopausal status. Optical spectroscopy can provide surgeons with intra-operative diagnostic tools. Here, we evaluate ex-vivo breast tissue and determine which sources of optical contrast have the potential to detect malignancy at the margins in women of differing breast composition. Methods Diffuse reflectance spectra were measured from 595 normal and 38 malignant sites from the margins of 104 partial mastectomy patients. All statistical tests were performed using Wilcoxon Rank-Sum tests. Normal and malignant sites were compared before stratifying the data by tissue type and depth and computing statistical differences. The frequencies of the normal tissue types were separated by menopausal status and compared to the corresponding optical properties. Results The mean reduced scattering coefficient, < μs' >, and concentration of total hemoglobin, [THb]), showed statistical differences between malignant (< μs' > : 8.96 cm-1 ± 2.24MAD, [THb]: 42.70 μM ± 29.31MAD) compared to normal sites (< μs' > : 7.29 cm-1 ± 2.15MAD, [THb]: 32.09 μM ± 16.73MAD) (P < 0.05). The sites stratified according to normal tissue type (fibro-glandular (FG), fibro-adipose (FA), and adipose (A)) or disease type (invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS)) showed that FG exhibited increased < μs' > and A showed increased [β-carotene] within normal tissues. Scattering differentiated between most malignant sites, DCIS (9.46 cm-1 ± 1.06MAD) and IDC (8.00 cm-1 ± 1.81MAD), versus A (6.50 cm-1 ± 1.95MAD). [β-carotene] showed marginal differences between DCIS (19.00 μM ± 6.93MAD

  14. IL-6 originated from breast cancer tissue-derived mesenchymal stromal cells may contribute to carcinogenesis.

    PubMed

    Sağlam, Özlem; Ünal, Zehra Seda; Subaşı, Cansu; Ulukaya, Engin; Karaöz, Erdal

    2015-07-01

    Tumor microenvironment is an important factor, which sustains and promotes the tumors by inflammatory signals. Interleukin-6 (IL-6) is known as a multifunctional cytokine, which is a major activator of the signaling pathway of Janus kinases (JAKs)/signal transducer and activator of transcription 3 (STAT3). In this study, we aimed to investigate the effect of IL-6 in the tumor microenvironment on carcinogenesis. For this purpose, healthy breast tissue-derived stromal cells (HBT-SCs) and malign breast tissue-derived stromal cells (MBT-SCs) were co-cultured with MCF-7 (human breast adenocarcinoma cell line) cells using semipermeable membranes. The cell proliferation was monitored with water-soluble tetrazolium (WST) and carboxyfluorescein succinimidyl ester (CFSE) assays. Protein levels were measured by enzyme-linked immunosorbent assay (ELISA) and Western blot hybridization, while gene expressions were measured by real-time PCR. The results demonstrated that IL-6 protein levels increased significantly in the supernatants of MBT-SCs when they were co-cultured with MCF-7 cells. In accordance with this, the expression of IL-6 was significantly higher in MBT-SCs. Additionally, the expression of STAT3 in MCF-7 cells increased slightly when they were co-cultured with MBT-SCs. Considering together, there is an important interaction between tumor microenvironment and tumor cells mediated by IL-6 signaling. Thereby, the targeting on IL-6 signaling in the treatment of cancer might effectively prevent the tumor progression. PMID:25697898

  15. Differential effects of progestins on breast tissue enzymes.

    PubMed

    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. PMID:14670645

  16. Evolving Concepts: How Diet and the Intestinal Microbiome Act as Modulators of Breast Malignancy

    PubMed Central

    Taioli, Emanuela

    2013-01-01

    The intestinal microbiome plays an important role in human physiology. Next-generation sequencing technologies, knockout and gnotobiotic mouse models, fecal transplant data and epidemiologic studies have accelerated our understanding of microbiome abnormalities seen in immune diseases and malignancies. Dysbiosis is the disturbed microbiome ecology secondary to external pressures such as host diseases, medications, diet and genetic conditions often leading to abnormalities of the host immune system. Specifically dysbiosis has been shown to lower circulating lymphocytes, and increase neutrophil to lymphocyte ratio, a finding which has been associated with a decreased survival in women with breast cancers. Dysbiosis also plays a role in the recycling of estrogens via the entero-hepatic circulation, increasing estrogenic potency in the host, which is another leading cause of breast malignancy. Non-modifiable factors such as age and genetic mutations disrupt the microbiome, but modifiable factors such as diet may also lead to profound disruptions as well. A better understanding of dietary factors and how they disrupt the microbiome may lead to beneficial nutritional interventions for breast cancer patients. PMID:24187630

  17. Malignant myoepithelioma of the breast: A case report and review of the literature

    PubMed Central

    PAPAZIAN, MARIA; KALANTZIS, IOANNIS; GALANOPOULOS, GEORGIOS; MANI, ILIANA; TZAIDA, OLYMPIA; IACOVIDOU, IOANNA; ZIRAS, NIKOLAOS

    2016-01-01

    Malignant myoepithelioma of the breast is an extremely rare tumor composed entirely or almost entirely of malignant spindle cells with myoepithelial differentiation. Only a limited number of case reports have been descibed to date; therefore the biological behavior and treatment outcomes of this rare tumor have not been clearly determined. Herein, we present a case of a 74-year-old woman who was admitted with inflammatory-like cancer of the breast, presenting with invasion of the chest wall and axillary lymph node metastasis at the time of diagnosis. The histological examination revealed a tumor composed of epithelioid and spindle cells with moderate to marked nuclear atypia, with foci of hemorrhage and necrosis. The tumor cells were immunoreactive for vimentin, p63, p53, CD10, cytokeratin (CK)8/18, CKAE1-3 and S-100. Finally, a diagnosis of myoepithelial carcinoma of the breast was established. Neoadjuvant chemotherapy was first administered and proved to be ineffective. Due to locoregional progression that was associated with the development of an abscess and subsequent excessive bleeding, a palliative mastectomy was performed. Postoperatively, one more cycle of systemic chemotherapy was administered. However, the patient experienced an early relapse to the chest wall and succumbed to septic shock due to persistent local infection. The aggressiveness and chemoresistance of the tumor in this case was consistent with the existing bibliography. PMID:27123270

  18. [On the possibility to determine genetic identity of the tissues with malignant tumours imbedded in paraffin blocks].

    PubMed

    Pigolkin, Yu I; Dolzhansky, O V; Korostylev, S A; Pal'tseva, E M; Fedorov, D N

    2016-01-01

    The results of analysis of the literature data were used to develop the forensic medical criteria for the assessment of the suitability of paraffin blocks containing the imbedded malignant tumours for the genetic identification of the tissues. The forensic medical criteria and the algorithm for the preliminary characteristic of the material of interest were proposed to avoid the potential errors. It is not recommended to use gastrointestinal carcinomas, breast tumours, and poorly differentiated ovarian tumours. Also unsuitable is the material formerly exposed to radio- and chemotherapeutic agents or paraffin blocks stored during more than 5-7 years. In the doubtful cases, immunohistochemical studies must be carried out to confirm microsatellite instability. Moreover, the tumour genotype and DNA composition from the patients' blood should be confirmed. PMID:27239766

  19. Uptake and distribution of fluorescently labeled cobalamin in neoplastic and healthy breast tissue

    NASA Astrophysics Data System (ADS)

    Cannon, Michelle J.; McGreevy, James M.; Holden, Joseph A.; West, Frederick G.; Grissom, Charles B.

    2000-05-01

    Fluorescent analogs of cobalamin (vitamin B12) have been developed as diagnostic markers of cancer cells. These compounds are recognized by transcobalamin, a cobalamin transport protein, with high affinity, as shown by surface plasmon resonance. The cellular sequestration and gross distribution of fluorescent cobalamin bioconjugates in breast tissue is being examined by epifluorescence microscopy. The distribution of each compound is being evaluated in proliferative and non-proliferative tissue, i.e. normal tissue and breast carcinoma. The results of preliminary studies suggest that fluorescent analogs of cobalamin may be a useful tool in therapeutic breast operations to define tumor margins and to distinguish neoplastic breast tissue from healthy breast tissue.

  20. Endothelial Cell Migration and Vascular Endothelial Growth Factor Expression Are the Result of Loss of Breast Tissue Polarity

    SciTech Connect

    Chen, Amy; Cuevas, Ileana; Kenny, Paraic A; Miyake, Hiroshi; Mace, Kimberley; Ghajar, Cyrus; Boudreau, Aaron; Bissell, Mina; Boudreau, Nancy

    2009-05-26

    Recruiting a new blood supply is a rate-limiting step in tumor progression. In a three-dimensional model of breast carcinogenesis, disorganized, proliferative transformed breast epithelial cells express significantly higher expression of angiogenic genes compared with their polarized, growth-arrested nonmalignant counterparts. Elevated vascular endothelial growth factor (VEGF) secretion by malignant cells enhanced recruitment of endothelial cells (EC) in heterotypic cocultures. Significantly, phenotypic reversion of malignant cells via reexpression of HoxD10, which is lost in malignant progression, significantly attenuated VEGF expression in a hypoxia-inducible factor 1{alpha}-independent fashion and reduced EC migration. This was due primarily to restoring polarity: forced proliferation of polarized, nonmalignant cells did not induce VEGF expression and EC recruitment, whereas disrupting the architecture of growth-arrested, reverted cells did. These data show that disrupting cytostructure activates the angiogenic switch even in the absence of proliferation and/or hypoxia and restoring organization of malignant clusters reduces VEGF expression and EC activation to levels found in quiescent nonmalignant epithelium. These data confirm the importance of tissue architecture and polarity in malignant progression.

  1. Epigenetic Inactivation of RASSF1A in Lung and Breast Cancers and Malignant Phenotype Suppression

    PubMed Central

    Burbee, David G.; Forgacs, Eva; Zöchbauer-Müller, Sabine; Shivakumar, Latha; Fong, Kwun; Gao, Boning; Randle, Dwight; Kondo, Masashi; Virmani, Arvind; Bader, Scott; Sekido, Yoshitaka; Latif, Farida; Milchgrub, Sara; Toyooka, Shinichi; Gazdar, Adi F.; Lerman, Michael I.; Zabarovsky, Eugene; White, Michael; Minna, John D.

    2015-01-01

    Background The recently identified RASSF1 locus is located within a 120-kilobase region of chromosome 3p21.3 that frequently undergoes allele loss in lung and breast cancers. We explored the hypothesis that RASSF1 encodes a tumor suppressor gene for lung and breast cancers. Methods We assessed expression of two RASSF1 gene products, RASSF1A and RASSF1C, and the methylation status of their respective promoters in 27 non-small-cell lung cancer (NSCLC) cell lines, in 107 resected NSCLCs, in 47 small-cell lung cancer (SCLC) cell lines, in 22 breast cancer cell lines, in 39 resected breast cancers, in 104 nonmalignant lung samples, and in three breast and lung epithelial cultures. We also transfected a lung cancer cell line that lacks RASSF1A expression with vectors containing RASSF1A complementary DNA to determine whether exogenous expression of RASSF1A would affect in vitro growth and in vivo tumorigenicity of this cell line. All statistical tests were two-sided. Results RASSF1A messenger RNA was expressed in nonmalignant epithelial cultures but not in 100% of the SCLC, in 65% of the NSCLC, or in 60% of the breast cancer lines. By contrast, RASSF1C was expressed in all nonmalignant cell cultures and in nearly all cancer cell lines. RASSF1A promoter hypermethylation was detected in 100% of SCLC, in 63% of NSCLC, in 64% of breast cancer lines, in 30% of primary NSCLCs, and in 49% of primary breast tumors but in none of the nonmalignant lung tissues. RASSF1A promoter hypermethylation in resected NSCLCs was associated with impaired patient survival (P = .046). Exogenous expression of RASSF1A in a cell line lacking expression decreased in vitro colony formation and in vivo tumorigenicity. Conclusion RASSF1A is a potential tumor suppressor gene that undergoes epigenetic inactivation in lung and breast cancers through hypermethylation of its promoter region. PMID:11333291

  2. Huge malignant phyllodes breast tumor: a real entity in a new era of early breast cancer.

    PubMed

    Testori, Alberto; Meroni, Stefano; Errico, Valentina; Travaglini, Roberto; Voulaz, Emanuele; Alloisio, Marco

    2015-01-01

    Phyllodes tumor is an extremely rare tumor of the breast. It occurs in females in the third and fourth decades. The difficulty in distinguishing between phyllodes tumors and benign fibroadenoma may lead to misdiagnosis. Lymph node involvement is rarely described in phyllodes tumors; for this reason, sentinel node biopsy may be warranted. We present a case of a 33-year-old woman affected by huge tumor of the right breast with ulceration in the skin with a rapid tumor growth and with omolateral axillary metastasis. PMID:25880837

  3. Trimodal spectra for high discrimination of benign and malignant prostate tissue

    NASA Astrophysics Data System (ADS)

    Al Salhi, Mohamad; Masilamani, Vadivel; Trinka, Vijmasi; Rabah, Danny; Al Turki, Mohammed R.

    2011-02-01

    High false positives and over diagnosis is a major problem with management of prostate cancer. A non-invasive or a minimally invasive technique to accurately distinguish malignant prostate cancers from benign tumors will be extremely helpful to overcome this problem. In this paper, we had used three different fluorescence spectroscopy techniques viz., Fluorescence Emission Spectrum (FES), Stokes' Shift Spectrum (SSS) and Reflectance Spectrum (RS) to discriminate benign prostate tumor tissues (N=12) and malignant prostate cancer tissues (N=8). These fluorescence techniques were used to determine the relative concentration of naturally occurring biomolecules such as tryptophan, elastin, NADH and flavin which are found to be out of proportion in cancer tissues. Our studies show that combining all three techniques, benign and malignant prostate tissues could be classified with accuracy greater than 90%. This preliminary report is based on in vitro spectroscopy analysis. However, by employing fluorescence endoscopy techniques, this can be extended to in vivo analysis as well. This technique has the potential to identify malignant prostate tissues without surgery.

  4. A tissue stabilization device for MRI-guided breast biopsy.

    PubMed

    Patriciu, Alexandru; Chen, Maggie; Iranpanah, Behzad; Sirouspour, Shahin

    2014-09-01

    We present a breast tissue stabilization device that can be used in magnetic resonance imaging-guided biopsy. The device employs adjustable support plates with an optimized geometry to minimize the biopsy target displacement using smaller compression than the conventional parallel plates approach. It is expected that the reduced compression will cause less patient discomfort and improve image quality by enhancing the contrast intake. Precomputed optimal positions of the stabilization plates for a given biopsy target location are provided in a look-up table. The results of several experiments with a prototype of the device carried out on chicken breast tissue demonstrate the effectiveness of the new design when compared with conventional stabilization methods. The proposed stabilization mechanism provides excellent flexibility in selecting the needle insertion point and can be used in manual as well as robot-assisted biopsy procedures. PMID:25023957

  5. A Rare Presentation Of An Ectopic Breast Tissue In Axilla.

    PubMed

    Vidyasagar, Radhika; Singh, R N

    2015-10-01

    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. PMID:26812754

  6. Breast cancer cell behaviors on staged tumorigenesis-mimicking matrices derived from tumor cells at various malignant stages

    SciTech Connect

    Hoshiba, Takashi; Tanaka, Masaru

    2013-09-20

    Highlights: •Models mimicking ECM in tumor with different malignancy were prepared. •Cancer cell proliferation was suppressed on benign tumor ECM. •Benign tumor cell proliferation was suppressed on cancerous ECM. •Chemoresistance of cancer cell was enhanced on cancerous ECM. -- Abstract: Extracellular matrix (ECM) has been focused to understand tumor progression in addition to the genetic mutation of cancer cells. Here, we prepared “staged tumorigenesis-mimicking matrices” which mimic in vivo ECM in tumor tissue at each malignant stage to understand the roles of ECM in tumor progression. Breast tumor cells, MDA-MB-231 (invasive), MCF-7 (non-invasive), and MCF-10A (benign) cells, were cultured to form their own ECM beneath the cells and formed ECM was prepared as staged tumorigenesis-mimicking matrices by decellularization treatment. Cells showed weak attachment on the matrices derived from MDA-MB-231 cancer cells. The proliferations of MDA-MB-231 and MCF-7 was promoted on the matrices derived from MDA-MB-231 cancer cells whereas MCF-10A cell proliferation was not promoted. MCF-10A cell proliferation was promoted on the matrices derived from MCF-10A cells. Chemoresistance of MDA-MB-231 cells against 5-fluorouracil increased on only matrices derived from MDA-MB-231 cells. Our results showed that the cells showed different behaviors on staged tumorigenesis-mimicking matrices according to the malignancy of cell sources for ECM preparation. Therefore, staged tumorigenesis-mimicking matrices might be a useful in vitro ECM models to investigate the roles of ECM in tumor progression.

  7. Complex permittivities of breast tumor tissues obtained from cancer surgeries

    NASA Astrophysics Data System (ADS)

    Sugitani, Takumi; Kubota, Shin-ichi; Kuroki, Shin-ichiro; Sogo, Kenta; Arihiro, Koji; Okada, Morihito; Kadoya, Takayuki; Hide, Michihiro; Oda, Miyo; Kikkawa, Takamaro

    2014-06-01

    The variability in measurements of complex permittivities of tumor tissues between multiple samples could be attributed to the volume fraction of cancer cells in the excised tumor tissue. By the use of a digital photomicrograph image and hematoxylin-eosin staining, it was found that the malignant tumor tissue was not fully occupied by the cancer cells, but the cells were distributed locally in the stroma cells depending on the growth of cancer. The results showed that the volume fraction of cancer cells in the tumor tissue had a correlation to the measured conductivity and dielectric constant in the frequency range from 1 GHz to 6 GHz. It introduces a method to understand and gauge variability in measurements between different tumors.

  8. [Malignant metastasizing cystosarcoma phylloides of the breast. Ulm collection of rare tumors: VI].

    PubMed

    Baczako, K; Fischer, H

    1984-12-01

    Malignant cystosarcoma phylloides represents the malignant form of mammary fibroadenoma. In spite of atypical epithelial components, the biological behaviour of the tumour depends on malignant transformation of the dominant mesenchymal stromal tissue in the tumour. The histological appearance, often extremely variable, usually corresponds to a fibrosarcoma. Lipoblastic, chondroid and myxoid structures or areas of ossification may be present, although a completely dedifferentiated cystosarcoma is rare. The epithelial structures which are typically canalicular may reveal hyperplastic and dysplastic changes as well as an apocrine change and occasionally squamous metaplasia. Besides aggressive local infiltration, hematogenous metastasis of the skeletal system and lungs is common. Therapy is dependent on the extent of local tumour growth as well as on the degree of metastasis and usually takes the form of radical mastectomy with lymphadenectomy and postoperative radiotherapy. Local recurrence is found in over 50% of the cases and the 5-year survival rate is in the order of 70%. PMID:6098887

  9. Predictive model for contrast-enhanced ultrasound of the breast: Is it feasible in malignant risk assessment of breast imaging reporting and data system 4 lesions?

    PubMed Central

    Luo, Jun; Chen, Ji-Dong; Chen, Qing; Yue, Lin-Xian; Zhou, Guo; Lan, Cheng; Li, Yi; Wu, Chi-Hua; Lu, Jing-Qiao

    2016-01-01

    AIM: To build and evaluate predictive models for contrast-enhanced ultrasound (CEUS) of the breast to distinguish between benign and malignant lesions. METHODS: A total of 235 breast imaging reporting and data system (BI-RADS) 4 solid breast lesions were imaged via CEUS before core needle biopsy or surgical resection. CEUS results were analyzed on 10 enhancing patterns to evaluate diagnostic performance of three benign and three malignant CEUS models, with pathological results used as the gold standard. A logistic regression model was developed basing on the CEUS results, and then evaluated with receiver operating curve (ROC). RESULTS: Except in cases of enhanced homogeneity, the rest of the 9 enhancement appearances were statistically significant (P < 0.05). These 9 enhancement patterns were selected in the final step of the logistic regression analysis, with diagnostic sensitivity and specificity of 84.4% and 82.7%, respectively, and the area under the ROC curve of 0.911. Diagnostic sensitivity, specificity, and accuracy of the malignant vs benign CEUS models were 84.38%, 87.77%, 86.38% and 86.46%, 81.29% and 83.40%, respectively. CONCLUSION: The breast CEUS models can predict risk of malignant breast lesions more accurately, decrease false-positive biopsy, and provide accurate BI-RADS classification. PMID:27358688

  10. Diagnostics of breast cancer tissue by fiber optic evanescent wave Fourier transform IR (FEW-FTIR) spectroscopy

    NASA Astrophysics Data System (ADS)

    Afanasyeva, Natalia I.; Makhine, Volodymyr; Bruch, Reinhard F.

    1999-06-01

    Fourier transform IR fiberoptic evanescent wave (FTIR-FEW) spectroscopy has been suggested as a powerful tool for clinical diagnostics of normal, pre-cancerous, and cancerous breast tissue ex vivo and in vitro in the middle IR region of the spectrum(850-1850 cm-1). This method is suitable for noninvasive and direct measurements of the spectra of normal and pathological tissues in vitro, ex vivo and in vivo. For the first time this method has been use nondestructively, rapidly, fast (15-20 sec) and remotely in the operating rooms of clinics. The aim of our studies has been the on-line testing of various tumor tissues during surgery to optimize and localize an area to remove tissue. We measured very small samples of normal and malignant breast tissue ex vivo with a fiber bent to a special angle, forming a special tip probe configuration. We also suggest here the minimally invasive FTIR-FEW diagnosis tool using 'needle' changeable tip probe for biopsy applications. The corresponding spectral histopathology scheme could be developed with help of this technique in vitro. The breast tissue at different stages of tumor or cancer has been distinguished very clearly in spectra of amide, cyclic and non-cyclic hydrogen bonded fragments, phosphate groups and sugars.

  11. Malignant pleural and pericardial effusions and meningeal infiltrates without other metastases in breast cancer: A case report

    PubMed Central

    LV, XINGXING; HE, JINLAN; SHEN, YUAN; ZHENG, HONG

    2016-01-01

    Breast cancer metastasizing to the pleura, pericardium and leptomeninges, but not to other sites, is rare. Although malignant pericardial and pleural effusions are common complications during the course of malignancies, they are rarely the initial manifestations of malignant disease, particularly pericardial effusion with cardiac tamponade. This report describes a case of breast carcinoma in a 44-year-old woman who initially presented with malignant pleural effusion and pericardial tamponade and suffered from meningeal metastases after 4.5 months. Unfortunately, the patient succumbed to pericardial tamponade 7 months later. There was no metastasis identified in other organs during the course of the disease. To the best of our knowledge, no similar case has been reported in the literature to date. PMID:27123295

  12. Diagnostic accuracy of shear wave elastography for prediction of breast malignancy in patients with pathological nipple discharge

    PubMed Central

    Guo, Xiaobo; Liu, Ying; Li, Wanhu

    2016-01-01

    Objectives Pathological nipple discharge (PND) may indicate malignant breast lesions. As the role of shear wave elastography (SWE) in predicting these malignant lesions has not yet been evaluated, we aim to evaluate the diagnostic value of SWE for this condition. Design Prospective diagnostic accuracy study comparing a combination of qualitative and quantitative measurements of SWE (index test) to a ductoscopy and microdochectomy for histological diagnosis (reference test). Setting Fuzhou General Hospital of Nanjing military command. Participants A total of 379 patients with PND were finally included from January, 2011 to March 2014, after we screened 1084 possible candidates. All participants were evaluated through SWE, with qualitative parameters generated by Virtual Touch tissue imaging (VTI) and quantitative parameters generated by Virtual Touch tissue quantification (VTQ). All the patients were consented to receive a ductoscopy and microdochectomy for histological diagnosis, and the results were set as a reference test. Outcome measures Sensitivity and specificity of the combined VTI and VTQ of the SWE for detection of malignancy in patients with PND. Results The 379 participants presented with 404 lesions. The results of pathological examination showed that 326 (80.7%) of the 404 lesions were benign and the other 78 (19.3%) were malignant. An area under the curve of elasticity score, VTQm and VTQc, were 0.872, 0.825 and 0.857, respectively, with the corresponding cut-off point as 2.50, 2.860 m/s and 3.015 m/s, respectively. After a combination of these measurements, the sensitivity, specificity, and positive and negative predictive value (PPV and NPV), were 89.7%, 72.1%, 43.5% and 96.7%, respectively. The sensitivity analysis showed 82% of the sensitivity and 96.8% of the specificity, in which patients with no pathological findings in ductoscopy were excluded. Conclusions Ultrasonographic elastography is sensitive for patients with PND and could be used

  13. FTIR microscopic comparative study on normal, premalignant, and malignant tissues of human intenstine

    NASA Astrophysics Data System (ADS)

    Mordechai, Shaul; Argov, Shmuel; Salman, Ahmad O.; Cohen, Beny; Ramesh, Jagannathan; Erukhimovitch, Vitaly; Goldstein, Jed; Sinelnikov, Igor

    2000-07-01

    Fourier-Transform Infrared Spectroscopy (FTIR) employs a unique approach to optical diagnosis of tissue pathology based on the characteristic molecular vibrational spectra of the tissue. The architectural changes in the cellular and sub-cellular levels developing in abnormal tissue, including a majority of cancer forms, manifest themselves in different optical signatures, which can be detected in infrared spectroscopy. The biological systems we have studied include normal, premalignant (polyp) and malignant human colonic tissues from three patients. Our method is based on microscopic infrared study (FTIR-microscopy) of thin tissue specimens and a direct comparison with normal histopathological analysis, which serves as a `gold' reference. The normal intestine tissue has a stronger absorption than polyp and cancerous types over a wide region in all three cases. The detailed analysis showed that there is a significant decrease in total phosphate and creatine contents for polyp and cancerous tissue types in comparison to the controls.

  14. A Rare Case of Breast Malignant Phyllodes Tumor With Metastases to the Kidney: Case Report.

    PubMed

    Karczmarek-Borowska, Bożenna; Bukala, Agnieszka; Syrek-Kaplita, Karolina; Ksiazek, Mariusz; Filipowska, Justyna; Gradalska-Lampart, Monika

    2015-08-01

    Phyllodes tumors are rare breast neoplasms. Surgery is the treatment of choice. The role of postoperative radiotherapy and chemotherapy is still under dispute, as there are no equivocal prognostic factors. Treatment failure results in the occurrence of distant metastasis-mainly to the lungs, bones, liver, and brain. We have described the case of a woman with a malignant phyllodes tumor of the breast that was surgically treated. She did not receive adjuvant therapy because there is no consensus on the role of postoperative chemotherapy and radiotherapy. One year following the surgery, the patient had left-sided nephrectomy performed because of a rapidly growing tumor of the kidney. Renal cancer was suspected; however, a histopathological examination revealed that it was a metastatic phyllodes tumor. At the same time, the patient was diagnosed as having metastases in the other kidney, the lungs, liver, and bones.Our case report describes not only an unusual localization of the metastases (in the kidneys), but also failure of the chemotherapy and the aggressive course of malignant phyllodes tumor. Identification of patients with high risk for distant metastasis and the introduction of uniform rules for the management of adjuvant chemotherapy and radiotherapy would make planning treatment as efficacious as possible. PMID:26287414

  15. A tyrosine phosphatase SHP2 gain-of-function mutation enhances malignancy of breast carcinoma

    PubMed Central

    Fang, Haoshu; Liu, Yakun; Chen, Danlei; Zhang, Qian; Liu, Xia; Wei, Daoyan; Qu, Chengkui; Wang, Siying

    2016-01-01

    Background: Evidence suggests that Src homologous protein phosphotyrosyl phosphatase 2 (SHP2) mutations promote cancer development in several solid tumours. In this study, we focused on the in vivo and in vitro effects of an SHP2 mutation on the breast cancer phenotype to determine whether this mutation is correlated with a malignant phenotype. Methods: Mutant PTPN11 cDNA (D61G) was transduced into MDA-MB231 and MCF-7 cells. The effects of the D61G mutation on tumourigenesis and malignant behaviours, such as cell adhesion, proliferation, migration and invasion, were examined. Potential underlying molecular mechanisms, i.e., activation of the Gab1-Ras-Erk axis, were also examined. Results: In vitro experiments revealed that tumour adhesion, proliferation, migration and invasion were significantly increased in the SHP2 D61G mutant groups. Consistently, in vivo experiments also showed that the tumour sizes and weights were increased significantly in the SHP2 D61G-MB231 group (p < 0.001) in association with tumour metastasis. Mechanistically, the PTPN11 mutation resulted in activation of the Ras-ErK pathway. The binding between Gab1 and mutant SHP2 was significantly increased. Conclusion: Mutant SHP2 significantly promotes tumour migration and invasion at least partially through activation of the Gab1-Ras-Erk axis. This finding could have direct implications for breast cancer therapy. PMID:26673822

  16. A Rare Case of Breast Malignant Phyllodes Tumor With Metastases to the Kidney

    PubMed Central

    Karczmarek-Borowska, Bożenna; Bukala, Agnieszka; Syrek-Kaplita, Karolina; Ksiazek, Mariusz; Filipowska, Justyna; Gradalska-Lampart, Monika

    2015-01-01

    Abstract Phyllodes tumors are rare breast neoplasms. Surgery is the treatment of choice. The role of postoperative radiotherapy and chemotherapy is still under dispute, as there are no equivocal prognostic factors. Treatment failure results in the occurrence of distant metastasis—mainly to the lungs, bones, liver, and brain. We have described the case of a woman with a malignant phyllodes tumor of the breast that was surgically treated. She did not receive adjuvant therapy because there is no consensus on the role of postoperative chemotherapy and radiotherapy. One year following the surgery, the patient had left-sided nephrectomy performed because of a rapidly growing tumor of the kidney. Renal cancer was suspected; however, a histopathological examination revealed that it was a metastatic phyllodes tumor. At the same time, the patient was diagnosed as having metastases in the other kidney, the lungs, liver, and bones. Our case report describes not only an unusual localization of the metastases (in the kidneys), but also failure of the chemotherapy and the aggressive course of malignant phyllodes tumor. Identification of patients with high risk for distant metastasis and the introduction of uniform rules for the management of adjuvant chemotherapy and radiotherapy would make planning treatment as efficacious as possible. PMID:26287414

  17. An EGFR/Src-dependent β4 integrin/FAK complex contributes to malignancy of breast cancer

    PubMed Central

    Tai, Yu-Ling; Chu, Pei-Yu; Lai, I-Rue; Wang, Ming-Yang; Tseng, Hui-Yuan; Guan, Jun-Lin; Liou, Jun-Yang; Shen, Tang-Long

    2015-01-01

    β4 integrin and focal adhesion kinase (FAK) are often associated with a poor prognosis in cancer patients, and their signaling events have recently been linked to malignant outcomes. Here, we demonstrate, for the first time, physical and functional interactions between β4 integrin and FAK that influence breast cancer malignancy. An amino-terminal linker within FAK is essential for its binding with the cytodomain of β4 integrin. Moreover, EGFR/Src-signaling triggers the tyrosine phosphorylation of β4 integrin, which, in turn, recruits FAK to β4 integrin and leads to FAK activation and signaling. Upon disruption of the β4 integrin/FAK complex, tumorigenesis and metastasis in triple-negative breast cancer were markedly reduced. Importantly, the concomitant overexpression of β4 integrin and FAK significantly correlates with malignant potential in patients with triple-negative breast cancer. This study describes a pro-metastatic EGFR/Src-dependent β4 integrin/FAK complex that is involved in breast cancer malignancy and is a novel therapeutic target for triple-negative breast cancer. PMID:26549523

  18. Near-infrared spectral tomography integrated with digital breast tomosynthesis: Effects of tissue scattering on optical data acquisition design

    SciTech Connect

    Michaelsen, Kelly; Krishnaswamy, Venkat; Pogue, Brian W.; Poplack, Steven P.; Paulsen, Keith D.

    2012-07-15

    Purpose: Design optimization and phantom validation of an integrated digital breast tomosynthesis (DBT) and near-infrared spectral tomography (NIRST) system targeting improvement in sensitivity and specificity of breast cancer detection is presented. Factors affecting instrumentation design include minimization of cost, complexity, and examination time while maintaining high fidelity NIRST measurements with sufficient information to recover accurate optical property maps. Methods: Reconstructed DBT slices from eight patients with abnormal mammograms provided anatomical information for the NIRST simulations. A limited frequency domain (FD) and extensive continuous wave (CW) NIRST system was modeled. The FD components provided tissue scattering estimations used in the reconstruction of the CW data. Scattering estimates were perturbed to study the effects on hemoglobin recovery. Breast mimicking agar phantoms with inclusions were imaged using the combined DBT/NIRST system for comparison with simulation results. Results: Patient simulations derived from DBT images show successful reconstruction of both normal and malignant lesions in the breast. They also demonstrate the importance of accurately quantifying tissue scattering. Specifically, 20% errors in optical scattering resulted in 22.6% or 35.1% error in quantification of total hemoglobin concentrations, depending on whether scattering was over- or underestimated, respectively. Limited frequency-domain optical signal sampling provided two regions scattering estimates (for fat and fibroglandular tissues) that led to hemoglobin concentrations that reduced the error in the tumor region by 31% relative to when a single estimate of optical scattering was used throughout the breast volume of interest. Acquiring frequency-domain data with six wavelengths instead of three did not significantly improve the hemoglobin concentration estimates. Simulation results were confirmed through experiments in two-region breast mimicking

  19. Automatic tissue segmentation of breast biopsies imaged by QPI

    NASA Astrophysics Data System (ADS)

    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.

  20. Classification of normal and malignant human gastric mucosa tissue with confocal Raman microspectroscopy and wavelet analysis

    NASA Astrophysics Data System (ADS)

    Hu, Yaogai; Shen, Aiguo; Jiang, Tao; Ai, Yong; Hu, Jiming

    2008-02-01

    Thirty-two samples from the human gastric mucosa tissue, including 13 normal and 19 malignant tissue samples were measured by confocal Raman microspectroscopy. The low signal-to-background ratio spectra from human gastric mucosa tissues were obtained by this technique without any sample preparation. Raman spectral interferences include a broad featureless sloping background due to fluorescence and noise. They mask most Raman spectral feature and lead to problems with precision and quantitation of the original spectral information. A preprocessed algorithm based on wavelet analysis was used to reduce noise and eliminate background/baseline of Raman spectra. Comparing preprocessed spectra of malignant gastric mucosa tissues with those of counterpart normal ones, there were obvious spectral changes, including intensity increase at ˜1156 cm -1 and intensity decrease at ˜1587 cm -1. The quantitative criterion based upon the intensity ratio of the ˜1156 and ˜1587 cm -1 was extracted for classification of the normal and malignant gastric mucosa tissue samples. This could result in a new diagnostic method, which would assist the early diagnosis of gastric cancer.

  1. Spectrum of Radiological Manifestations in Lymphoproliferative Malignancies with Unusual Extra Nodal Soft Tissue Involvement

    PubMed Central

    Prasad, Kahila; Upreti, Lalendra; Garga, Umesh Chandra

    2016-01-01

    Lymphoproliferative malignancies constitute a wide spectrum of haematological malignancies and their prevalence is widely increasing. Non-Hodgkin lymphomas and Hodgkin disease, frequently involve extranodal soft tissue structures in the head and neck, thorax and abdomen. These malignancies may involve virtually any type of soft tissues to any extent; hence many different imaging manifestations are possible which may mimic other disorders. The imaging characteristics of extranodal lymphomatous soft tissue involvement are described and classified here according to the site of involvement in 6 cases (primary diseases with orbital, muscle, extra testicular, scalp, sinonasal and pachymeningeal/dural involvement). In majority of these cases at presentation we found a predominantly homogeneous soft tissue mass with mildly high attenuation on CT and a T2 intermediate signal on MRI at these sites without any manifestation of disease elsewhere but on follow-up two out of these six cases developed systemic disease elsewhere. Few consistent patterns were noticed on CT and MRI which might help to include lymphomas as an important differential diagnosis of soft tissue masses. Though a definitive diagnosis requires a biopsy (bone marrow, lymph node, or mass), and other laboratory tests, imaging primarily aims at staging of the disease and identification of new or recurrent disease.

  2. Carcinoma originating from aberrant breast tissue of the right upper anterior chest wall : a case report.

    PubMed Central

    Rho, J. Y.; Juhng, S. K.; Yoon, K. J.

    2001-01-01

    Aberrant breast tissue is usually found in proximity to the normal breast, that is, in the axillary, sternal or clavicular regions. Carcinoma occurs more frequently in the aberrant tissue of the axilla than the extra-axillary site though the overall incidence of tumors of aberrant breast tissue is low. To our knowledge, studies regarding the carcinoma of aberrant breast tissue of the extra-axillary site have been reported rarely. Here we report a recent case of carcinoma originating from the extra-axillary aberrant breast tissue, presenting as a subcutaneous nodule on the right upper anterior chest wall. It is suggested that subcutaneous nodules of uncertain origin around the periphery of the breast should be suspected for breast carcinoma as a differential diagnosis and treated properly. PMID:11511802

  3. First International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions).

    PubMed

    Rageth, Christoph J; O'Flynn, Elizabeth Am; Comstock, Christopher; Kurtz, Claudia; Kubik, Rahel; Madjar, Helmut; Lepori, Domenico; Kampmann, Gert; Mundinger, Alexander; Baege, Astrid; Decker, Thomas; Hosch, Stefanie; Tausch, Christoph; Delaloye, Jean-François; Morris, Elisabeth; Varga, Zsuzsanna

    2016-09-01

    The purpose of this study is to obtain a consensus for the therapy of B3 lesions. The first International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions) including atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), classical lobular neoplasia (LN), papillary lesions (PL), benign phyllodes tumors (PT), and radial scars (RS) took place in January 2016 in Zurich, Switzerland organized by the International Breast Ultrasound School and the Swiss Minimally Invasive Breast Biopsy group-a subgroup of the Swiss Society of Senology. Consensus recommendations for the management and follow-up surveillance of these B3 lesions were developed and areas of research priorities were identified. The consensus recommendation for FEA, LN, PL, and RS diagnosed on core needle biopsy or vacuum-assisted biopsy (VAB) is to therapeutically excise the lesion seen on imaging by VAB and no longer by open surgery, with follow-up surveillance imaging for 5 years. The consensus recommendation for ADH and PT is, with some exceptions, therapeutic first-line open surgical excision. Minimally invasive management of selected B3 lesions with therapeutic VAB is acceptable as an alternative to first-line surgical excision. PMID:27522516

  4. Surface-enhanced Raman spectroscopy for differentiation between benign and malignant thyroid tissues

    NASA Astrophysics Data System (ADS)

    Li, Zuanfang; Li, Chao; Lin, Duo; Huang, Zufang; Pan, Jianji; Chen, Guannan; Lin, Juqiang; Liu, Nenrong; Yu, Yun; Feng, Shangyuan; Chen, Rong

    2014-04-01

    The aim of this study was to evaluate the potential of applying silver nano-particle based surface-enhanced Raman scattering (SERS) to discriminate different types of human thyroid tissues. SERS measurements were performed on three groups of tissue samples including thyroid cancers (n = 32), nodular goiters (n = 20) and normal thyroid tissues (n = 25). Tentative assignments of the measured tissue SERS spectra suggest interesting cancer specific biomolecular differences. The principal component analysis (PCA) and linear discriminate analysis (LDA) together with the leave-one-out, cross-validated technique yielded diagnostic sensitivities of 92%, 75% and 87.5%; and specificities of 82.6%, 89.4% and 84.4%, respectively, for differentiation among normal, nodular and malignant thyroid tissue samples. This work demonstrates that tissue SERS spectroscopy associated with multivariate analysis diagnostic algorithms has great potential for detection of thyroid cancer at the molecular level.

  5. The Potential of High Resolution Magnetic Resonance Microscopy in the Pathologic Analysis of Resected Breast and Lymph Tissue

    PubMed Central

    Dashevsky, Brittany Z.; D'Alfonso, Timothy; Sutton, Elizabeth J.; Giambrone, Ashley; Aronowitz, Eric; Morris, Elizabeth A.; Juluru, Krishna; Ballon, Douglas J.

    2015-01-01

    Pathologic evaluation of breast specimens requires a fixation and staining procedure of at least 12 hours duration, delaying diagnosis and post-operative planning. Here we introduce an MRI technique with a custom-designed radiofrequency resonator for imaging breast and lymph tissue with sufficient spatial resolution and speed to guide pathologic interpretation and offer value in clinical decision making. In this study, we demonstrate the ability to image breast and lymphatic tissue using 7.0 Tesla MRI, achieving a spatial resolution of 59 × 59 × 94 μm3 with a signal-to-noise ratio of 15–20, in an imaging time of 56 to 70 minutes. These are the first MR images to reveal characteristic pathologic features of both benign and malignant breast and lymph tissue, some of which were discernible by blinded pathologists who had no prior training in high resolution MRI interpretation. PMID:26639673

  6. The Potential of High Resolution Magnetic Resonance Microscopy in the Pathologic Analysis of Resected Breast and Lymph Tissue.

    PubMed

    Dashevsky, Brittany Z; D'Alfonso, Timothy; Sutton, Elizabeth J; Giambrone, Ashley; Aronowitz, Eric; Morris, Elizabeth A; Juluru, Krishna; Ballon, Douglas J

    2015-01-01

    Pathologic evaluation of breast specimens requires a fixation and staining procedure of at least 12 hours duration, delaying diagnosis and post-operative planning. Here we introduce an MRI technique with a custom-designed radiofrequency resonator for imaging breast and lymph tissue with sufficient spatial resolution and speed to guide pathologic interpretation and offer value in clinical decision making. In this study, we demonstrate the ability to image breast and lymphatic tissue using 7.0 Tesla MRI, achieving a spatial resolution of 59 × 59 × 94 μm(3) with a signal-to-noise ratio of 15-20, in an imaging time of 56 to 70 minutes. These are the first MR images to reveal characteristic pathologic features of both benign and malignant breast and lymph tissue, some of which were discernible by blinded pathologists who had no prior training in high resolution MRI interpretation. PMID:26639673

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

    PubMed Central

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

    2015-01-01

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

  8. Cysts within Otherwise Probably Benign Solid Breast Masses and the Risk of Malignancy.

    PubMed

    Jales, Rodrigo Menezes; Araujo, Karla Galvão; Sarian, Luis Otávio Zanata; Serra, Kátia Piton; Keppke, Helena; Francisco, Juliana; Derchain, Sophie Françoise Mauricette

    2016-04-01

    Objective The objective of this study is to assess whether the largest cyst diameter is useful for BI-RADS ultrasonography classification of predominantly solid breast masses with an oval shape, circumscribed margins, and largest axis parallel to the skin, which, except for the cystic component, would be likely classified as benign. Methods This study received approval from the local institutional review board. From March 2009 to August 2014, we prospectively biopsied 170 breast masses from 164 women. We grouped the largest cyst and mass diameters according to histopathological diagnoses. We used Student's t-test, linear regression, and the area under the receiver operating characteristic curve (AUC) for statistical assessment. Results Histopathological examination revealed 143 (84%) benign and 27 (16%) malignant masses. The mean largest mass diameter was larger among malignant (mean ± standard deviation, 34.1 ± 16.6 mm) than benign masses (24.7 ± 16.7 mm) (P < 0.008). The mean largest cyst diameter was also larger among malignant (9.9 ± 7.1 mm) than benign masses (4.6 ± 3.6 mm) (P < 0.001). Agreement between measurements of the largest mass and cyst diameters was low (R(2) = 0.26). AUC for the largest cyst diameter (0.78) was similar to the AUC for the largest mass diameter (0.69) (p = 0.2). A largest cyst diameter < 3, ≥ 3 to < 11, and ≥ 11 mm had a positive predictive value of 0, 15, and 52%, respectively. Conclusion A largest cystic component < 3 mm identified within breast masses that show favorable characteristics may be considered clinically inconsequential in ultrasonography characterization. Conversely, masses with a largest cystic component ≥ 3 mm should be classified as BI-RADS-US category 4. PMID:27093646

  9. FT-IR Spectroscopic Analysis of Normal and Malignant Human Oral Tissues

    NASA Astrophysics Data System (ADS)

    Krishnakumar, N.; Madhavan, R. Nirmal; Sumesh, P.; Palaniappan, Pl. Rm.; Venkatachalam, P.; Ramachandran, C. R.

    2008-11-01

    FT-IR spectroscopy has been used to explore the changes in the vibrational bands of normal and oral squamous cell carcinoma (OSCC) tissues in the region 4000-400 cm-1. Significant changes in the spectral features were observed. The spectral changes were the results of characteristics structural alterations at the molecular level in the malignant tissues. These alterations include structural changes of proteins and possible increase of its content, an increase in the nucleic-to-cytoplasm ratio, an increase in the relative amount of DNA, an increase in the rate of phosphorylation process induced by carcinogenesis, a loss of hydrogen bonding of the C-OH groups in the amino acid residues of proteins, a decrease in the relative amount of lipids compared to normal epithelial oral tissues. The results of the present study demonstrate that the FT-IR technique has the feasibility of discriminating malignant from normal tissues and other pathological states in a short period of time and may detect malignant transformation earlier than the standard histological examination stage.

  10. Initial study of breast tissue retraction toward image guided breast surgery

    NASA Astrophysics Data System (ADS)

    Shannon, Michael J.; Meszoely, Ingrid M.; Ondrake, Janet E.; Pheiffer, Thomas S.; Simpson, Amber L.; Sun, Kay; Miga, Michael I.

    2012-02-01

    Image-guided surgery may reduce the re-excision rate in breast-conserving tumor-resection surgery, but image guidance is difficult since the breast undergoes significant deformation during the procedure. In addition, any imaging performed preoperatively is usually conducted in a very different presentation to that in surgery. Biomechanical models combined with low-cost ultrasound imaging and laser range scanning may provide an inexpensive way to provide intraoperative guidance information while also compensating for soft tissue deformations that occur during breast-conserving surgery. One major cause of deformation occurs after an incision into the tissue is made and the skin flap is pulled back with the use of retractors. Since the next step in the surgery would be to start building a surgical plane around the tumor to remove cancerous tissue, in an image-guidance environment, it would be necessary to have a model that corrects for the deformation caused by the surgeon to properly guide the application of resection tools. In this preliminary study, two anthropomorphic breast phantoms were made, and retractions were performed on both with improvised retractors. One phantom underwent a deeper retraction that the other. A laser range scanner (LRS) was used to monitor phantom tissue change before and after retraction. The surface data acquired with the LRS and retractors were then used to drive the solution of a finite element model. The results indicate an encouraging level of agreement between model predictions and data. The surface target error for the phantom with the deep retraction was 2.2 +/- 1.2 mm (n=47 targets) with the average deformation of the surface targets at 4.2 +/- 1.6mm. For the phantom with the shallow retraction, the surface target error was 2.1 +/- 1.0 mm (n=70 targets) with the average deformation of the surface targets at 4.0 +/- 2.0 mm.

  11. [Binding capability of lidamycin apoprotein to human breast cancer detected by tissue microarrays].

    PubMed

    Cai, Lin; Gao, Rui-Juan; Guo, Xiao-Zhong; Li, Yi; Zhen, Yong-Su

    2010-05-01

    This study is to investigate the binding capability of lidamycin apoprotein (LDP), an enediyne-associated apoprotein of the chromoprotein antitumor antibiotic family, to human breast cancer and normal tissues, the correlation of LDP binding capability to human breast cancer tissues and the expression of tumor therapeutic targets such as VEGF and HER2. In this study, the binding capability of LDP to human breast cancer tissues was detected with tissue microarray. The correlation study of LDP binding capability to human breast tumor tissues and relevant therapeutic targets was performed on breast cancer tissue microarrays. Immunocytochemical examination was used to detect the binding capability of LDP to human breast carcinoma MCF-7 cells. As a result, tissue microarray showed that LDP staining of 73.2% (30/41) of breast cancer tissues was positive, whereas that of 48.3% (15/31) of the adjacent normal breast specimens was positive. The difference between the tumor and normal samples was significant (Chi2 = 4.63, P < 0.05). LDP immunoreactivity in breast cancer correlated significantly with the overexpression of VEGF and HER2 (P < 0.001 and < 0.01, r = 0.389 and 0.287, respectively). Determined with confocal immunofluorescent analysis, LDP showed the binding capability to mammary carcinoma MCF-7 cells. It is demonstrated that LDP can bind to human breast cancer tissues and there is significant difference between the breast cancer tissues and the corresponding normal tissues. Notably, the binding reactivity shows positive correlation with the expression of VEGF and HER2 in breast carcinoma tissues. The results imply that LDP may have a potential use as targeting drug carrier in the research and development of new anticancer therapeutics. This study may provide reference for drug combination of LDM and other therapeutic agents. PMID:20931759

  12. Loss of antigenicity with tissue age in breast cancer.

    PubMed

    Combs, Susan E; Han, Gang; Mani, Nikita; Beruti, Susan; Nerenberg, Michael; Rimm, David L

    2016-03-01

    Archived tumor specimens, particularly those collected by large cooperative groups and trials, provide a wealth of material for post hoc clinical investigation. As these tissues are rigorously collected and preserved for many decades, subsequent use of the specimens to answer clinical questions must rely on the assumption that expression and detection of target biomarkers are not degraded with time. To test this assumption, we measured the expression of estrogen receptor (ER), human epidermal growth receptor 2 (HER2), and Ki67 in human breast carcinoma using quantitative immunofluorescence (QIF) in a series of formalin-fixed paraffin-embedded (FFPE) tissues from 1295 individual patients preserved for 7 to 53 years in four cohorts on tissue microarrays. Protein expression was measured using the automated quantitative analysis method for QIF. Change in quantitative protein expression over time was estimated in positive cases using both Pearson's correlation and a polynomial regression analysis with a random effects model. The average signal decreased with preservation time for all biomarkers measured. For ER and HER2, there was an average of 10% signal loss after 9.9 years and 8.5 years, respectively, compared with the most recent tissue. Detection of Ki67 expression was lost more rapidly, with 10% signal loss in just 4.5 years. Overall, these results demonstrate the need for adjustment of tissue age when studying FFPE biospecimens. The rate of antigenicity loss is biomarker specific and should be considered as an important variable for studies using archived tissues. PMID:26568292

  13. Orthosis reduces breast pain and mechanical forces through natural and augmented breast tissue in women lying prone

    PubMed Central

    2014-01-01

    Background Breast implant displacement or rupture can cause aesthetic problems and serious medical complications. Activities with prone positioning and loading of the anterior chest wall, such as massage, chiropractic or osteopathic therapies may increase the risk of implant failure and can also cause discomfort in women with natural breast tissue. Here we test the effectiveness of a newly developed orthosis on pain, mechanical pressure and displacement of breast tissue in women with cosmetic augmentation, post-mastectomy reconstruction, lactating or natural breast tissue. Methods Thirty-two females volunteers, aged 25–56 years with augmented, reconstructed, natural or lactating breast tissue and cup sizes B-F, participated in this open-label clinical trial. We measured pain perception, peak pressure, maximum force, and breast tissue displacement using different sizes of the orthosis compared to no orthosis. Different densities of the orthosis were also tested in a subgroup of women (n = 7). Pain perception was rated using a validated 11-point visual-analogue scale. Peak pressure and maximum force were assessed using a bilateral set of capacitance-pliance® sensor strips whilst participants were load bearing in a prone position, and breast displacement was measured by magnetic-resonance-imaging. Results The orthosis significantly reduced pain, breast displacement and mechanical pressures in women with natural and augmented breast tissue in prone position. Greater relief of pain and greater reduction in mechanical forces were found with increased size and density of the orthosis. Use of the orthosis improved overall comfort by 64-100%, lowered peak pressure by up to 85% and maximum force by up to 96%. Medio-lateral displacement of breast tissue was reduced by 16%, resulting in a 51% desirable increase of breast tissue height. Conclusion Our study demonstrated that the newly developed orthosis significantly reduced pain, mechanical pressure and breast tissue

  14. Giant malignant phyllodes tumor of the breast: A rare case report and literature review

    PubMed Central

    LIU, MIN; YANG, SHUO; LIU, BIN; GUO, LIANG; BAO, XUEYING; LIU, BAILONG; DONG, LIHUA

    2016-01-01

    Malignant phyllodes tumor of the breast (MPTB) is rarely encountered in clinical practice. Preoperative diagnosis is challenging due to nonspecific radiological and histological features, and the prognostic factors and optimal treatment remain controversial. The current report describes the case of a middle-aged female with giant MPTB who underwent multidisciplinary intervention, including surgery, postoperative chemotherapy and radiotherapy. To date, the disease-free survival (DFS) of the patient has reached 18 months. Furthermore, a related literature review summarize the clinicopathological characteristics and treatment progress regarding MPTB is presented, along with an analysis of the indications for therapeutic strategy in the current case. In the future, multi-center clinical trials must be initiated to identify the criteria for diagnosis and optimal treatment consensus for MPTB. In conclusion, the present case highlights that multidisciplinary management may contribute to DFS following the treatment of giant MPTB. PMID:27347111

  15. Breast lesions of uncertain malignant nature and limited metastatic potential: Proposals to improve their recognition and clinical management

    PubMed Central

    Rakha, Emad A.; Badve, Sunil; Eusebi, Vincenzo; Reis-Filho, Jorge S.; Fox, Stephen B.; Dabbs, David J.; Decker, Thomas; Hodi, Zsolt; Ichihara, Shu; Lee, Andrew HS.; Palacios, José; Richardson, Andrea L.; Vincent-Salomon, Anne; Schmitt, Fernando C.; Tan, Puay-Hoon; Tse, Gary M.; Ellis, Ian O.

    2016-01-01

    Breast lesions comprise a family of heterogeneous entities with variable patterns of presentation, morphology and clinical behaviour. The majority of breast lesions are traditionally classified into benign and malignant conditions and their behaviour can, in the vast majority of cases, be predicted with a reasonable degree of accuracy. However, there remain lesions which show borderline features and lie in a grey-zone between benign and malignant as their behaviour cannot be predicted reliably. Defined pathological categorisation of such lesions is challenging and for some entities is recognised to be subjective and include a range of diagnoses, and forms of terminology, which may trigger over-treatment or under-treatment. The rarity of these lesions makes acquisition of clinical evidence problematic and limits the development of a sufficient evidence base to support informed decision making by clinicians and patients. Emerging molecular evidence is providing a greater understanding of the biology of these lesions, but this may or may not be reflected in their clinical behaviour. Herein we discuss some breast lesions that are associated with uncertainty regarding classification, behaviour and hence management. These include biologically invasive malignant lesions associated with uncertain metastatic potential such as low-grade adenosquamous carcinoma, low-grade fibromatosis-like spindle cell carcinoma and encapsulated papillary carcinoma. Other lesions remain of uncertain malignant nature such as mammary cylindroma, atypical microglandular adenosis, mammary pleomorphic adenoma and infiltrating epitheliosis. The concept of categories of 1) breast lesions of uncertain malignant nature and 2) breast lesions of limited metastatic potential, are proposed with details of which histological entities could be included in each category, and their management implications are discussed. PMID:26348644

  16. Breast lesions of uncertain malignant nature and limited metastatic potential: proposals to improve their recognition and clinical management.

    PubMed

    Rakha, Emad A; Badve, Sunil; Eusebi, Vincenzo; Reis-Filho, Jorge S; Fox, Stephen B; Dabbs, David J; Decker, Thomas; Hodi, Zsolt; Ichihara, Shu; Lee, Andrew H S; Palacios, José; Richardson, Andrea L; Vincent-Salomon, Anne; Schmitt, Fernando C; Tan, Puay-Hoon; Tse, Gary M; Ellis, Ian O

    2016-01-01

    Breast lesions comprise a family of heterogeneous entities with variable patterns of presentation, morphology and clinical behaviour. The majority of breast lesions are classified traditionally into benign and malignant conditions and their behaviour can, in the vast majority of cases, be predicted with a reasonable degree of accuracy. However, there remain lesions which show borderline features and lie in a grey zone between benign and malignant, as their behaviour cannot be predicted reliably. Defined pathological categorization of such lesions is challenging, and for some entities is recognized to be subjective and include a range of diagnoses, and forms of terminology, which may trigger over- or undertreatment. The rarity of these lesions makes the acquisition of clinical evidence problematic and limits the development of a sufficient evidence base to support informed decision-making by clinicians and patients. Emerging molecular evidence is providing a greater understanding of the biology of these lesions, but this may or may not be reflected in their clinical behaviour. Herein we discuss some breast lesions that are associated with uncertainty regarding classification and behaviour, and hence management. These include biologically invasive malignant lesions associated with uncertain metastatic potential, such as low-grade adenosquamous carcinoma, low-grade fibromatosis-like spindle cell carcinoma and encapsulated papillary carcinoma. Other lesions of uncertain malignant nature remain, such as mammary cylindroma, atypical microglandular adenosis, mammary pleomorphic adenoma and infiltrating epitheliosis. The concept of categories of (1) breast lesions of uncertain malignant nature and (2) breast lesions of limited metastatic potential are proposed with details of which histological entities could be included in each category, and their management implications are discussed. PMID:26348644

  17. Breast sarcomas and malignant phyllodes tumours: comparison of clinicopathological features, treatment strategies, prognostic factors and outcomes.

    PubMed

    Lim, Sue Zann; Selvarajan, Sathiyamoorthy; Thike, Aye Aye; Nasir, Nur Diyana Binte Md; Tan, Benita Kiat Tee; Ong, Kong Wee; Tan, Puay Hoon

    2016-09-01

    We aimed to compare the clinicopathological features, treatment strategies and clinical outcomes of breast sarcomas (BS) and malignant phyllodes tumours (MPT), and determine their prognostic factors. Cases of BS and MPT diagnosed at the Department of Pathology, Singapore General Hospital from January 1991 to December 2014 were derived from department files. Clinicopathological features, treatment strategies and survivals of patients with BS and MPT were compared. Prognostic indicators for BS and MPT were identified. BS and MPT were comparable in all except one of their clinicopathological features. A significantly higher proportion of BS patients had a history of previous breast carcinoma and thus radiation to the chest as compared to the MPT group (17.6 vs 0 %, P = 0.018). There was no significant difference in survival outcomes between BS and MPT. The 5-year disease-free survivals (DFS) for BS and MPT were 59.1 and 57.4 % respectively (P = 0.816), while the 5-year overall survivals (OS) for BS and MPT were 86.5 and 78.5 % respectively (P = 0.792). Combining both groups of tumours, univariate analysis showed that DFS was significantly affected by multifocality (P = 0.019), histological subtype (P = 0.014), presence of malignant heterologous elements (P < 0.001) and margin status (P = 0.023). Margin status was the only parameter which had a significant impact on OS (P = 0.040). Multivariate analysis confirmed the above findings. BS and MPT are rare entities with remarkable heterogeneity. They share similar clinicopathological features and outcomes, provoking thoughts on their biological relationship and clinical significance of pathologic distinction. PMID:27541020

  18. Optical Spectral Surveillance of Breast Tissue Landscapes for Detection of Residual Disease in Breast Tumor Margins

    PubMed Central

    Kennedy, Stephanie A.; Caldwell, Matthew L.; Gallagher, Jennifer E.; Junker, Marlee; Wilke, Lee G.; Barry, William T.; Geradts, Joseph; Ramanujam, Nimmi

    2013-01-01

    We demonstrate a strategy to “sense” the micro-morphology of a breast tumor margin over a wide field of view by creating quantitative hyperspectral maps of the tissue optical properties (absorption and scattering), where each voxel can be deconstructed to provide information on the underlying histology. Information about the underlying tissue histology is encoded in the quantitative spectral information (in the visible wavelength range), and residual carcinoma is detected as a shift in the histological landscape to one with less fat and higher glandular content. To demonstrate this strategy, fully intact, fresh lumpectomy specimens (n = 88) from 70 patients were imaged intra-operatively. The ability of spectral imaging to sense changes in histology over large imaging areas was determined using inter-patient mammographic breast density (MBD) variation in cancer-free tissues as a model system. We discovered that increased MBD was associated with higher baseline β-carotene concentrations (p = 0.066) and higher scattering coefficients (p = 0.007) as measured by spectral imaging, and a trend toward decreased adipocyte size and increased adipocyte density as measured by histological examination in BMI-matched patients. The ability of spectral imaging to detect cancer intra-operatively was demonstrated when MBD-specific breast characteristics were considered. Specifically, the ratio of β-carotene concentration to the light scattering coefficient can report on the relative amount of fat to glandular density at the tissue surface to determine positive margin status, when baseline differences in these parameters between patients with low and high MBD are taken into account by the appropriate selection of threshold values. When MBD was included as a variable a priori, the device was estimated to have a sensitivity of 74% and a specificity of 86% in detecting close or positive margins, regardless of tumor type. Superior performance was demonstrated in high

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

    PubMed

    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. PMID:18003206

  20. Near-infrared laser speckle imaging of human breast tissue

    NASA Astrophysics Data System (ADS)

    Bean, Robert Speer

    Current methods of breast cancer diagnostics (self-exam, clinical exam, x-ray mammography) fail to diagnose a significant number of cases while still in readily operable stages. This is especially true in younger women, where fibrotic tissue reduces the efficacy of x-ray mammography. Near infrared (NIR) laser photons pass diffusively through human tissue, creating a speckle pattern in a detector after transmission. The high and low intensity variations of the speckle have the appearance of random noise, but are not. The speckle pattern will have an intensity distribution that is informative about the scattering and absorption properties of the tissue that is imaged. Adaptations to the Los Alamos National Laboratory MCNP code are described that allow simulation of NIR laser transport through human tissue. A HeNe laser was used to create laser intensity patterns via transmission through homogeneous and non-homogeneous tissue phantoms. The Kolmogorov-Smirnov test was used to compare the cumulative distribution functions of the laser intensity patterns, and identify the presence of a non-homogeneity. Laser speckle techniques offer the ability to image tumors with few (<3) millimeter resolution without ionizing radiation dose.

  1. Measurement of bioelectric and acoustic profile of breast tissue using hybrid magnetoacoustic method for cancer detection.

    PubMed

    Salim, M I Mohamad; Supriyanto, E; Haueisen, J; Ariffin, I; Ahmad, A H; Rosidi, B

    2013-04-01

    This paper proposes a novel hybrid magnetoacoustic measurement (HMM) system aiming at breast cancer detection. HMM combines ultrasound and magnetism for the simultaneous assessment of bioelectric and acoustic profiles of breast tissue. HMM is demonstrated on breast tissue samples, which are exposed to 9.8 MHz ultrasound wave with the presence of a 0.25 Tesla static magnetic field. The interaction between the ultrasound wave and the magnetic field in the breast tissue results in Lorentz Force that produces a magnetoacoustic voltage output, proportional to breast tissue conductivity. Simultaneously, the ultrasound wave is sensed back by the ultrasound receiver for tissue acoustic evaluation. Experiments are performed on gel phantoms and real breast tissue samples harvested from laboratory mice. Ultrasound wave characterization results show that normal breast tissue experiences higher attenuation compared with cancerous tissue. The mean magnetoacoustic voltage results for normal tissue are lower than that for the cancerous tissue group. In conclusion, the combination of acoustic and bioelectric measurements is a promising approach for breast cancer diagnosis. PMID:23238828

  2. Micro-Ft Spectroscopic Studies of Breast Tissues

    NASA Astrophysics Data System (ADS)

    Anastassopoulou, J.; Arapantoni, P.; Boukaki, E.; Konstadoudakis, S.; Theophanides, T.; Valavanis, C.; Conti, C.; Ferraris, P.; Giorgini, G.; Sabbatini, S.; Tosi, G.

    Micro-FT-IR spectroscopy was used to study breast cancer tissues and, in particular osteosarcoma tissue. By analysing the spectra, we have found characteristic bands in the infrared regions, where the main components of these signature bands are located. In the region between 1680-1660 cm-1 are found the characteristic bands of Amide I and II of proteins. The bands, which correspond to the vibrations of the phosphate groups, are found in the region near 1140-900 cm-1. These characteristic bands have been monitored as a function of the degree of cancer progression. The results have been obtained with chemometric methods, such as cluster analysis, principal component analysis and custom analysis in order to distinguish the neoplastic zones from the normal zones.

  3. A technique for marking oncological breast tissue specimens.

    PubMed

    Patel, Jaison; Jenkins, Stephanie

    2016-05-01

    With new breast conserving oncological surgical techniques, accurate identification of specimen margins is important to allow for the re-excision of margins. The accurate identification of margins is crucial is the success of the patients treatment if further margins are required. NHS Breast Screening Programme (NHSBSP) guidelines recommend the excised specimen is labelled accurately to correctly identify the margins and allow for X-ray examination. This method has been proven to be cheap, it uses equipment and materials readily available in the operating theatre. Furthermore, if any of the methods fails as there is more than one way to identifying your margins. For example if a clip were to fall off, the type/length of suture and the orientation on the board will still allow you to identify the correct margin. If the sample was to fall off the board, the sutures and clips will still allow the pathologist to orientate the sample. In summary this method is easy to apply, logical and uses equipment readily available within the theatre, i.e. silk sutures, and the needle protection board. It ensures all relevant radiological and surgical criteria are met for enabling orientation of the specimen when removed from the breast tissue. It is an easily taught technique that is easy to remember. A national survey showed a lack and wide variation of specimen orientation protocols. (Volleamere et al., 2013) This technique could be used as the national standard for breast specimen marking and as a national marking system for the NHS. PMID:27158488

  4. New method for generating breast models featuring glandular tissue spatial distribution

    NASA Astrophysics Data System (ADS)

    Paixão, L.; Oliveira, B. B.; Oliveira, M. A.; Teixeira, M. H. A.; Fonseca, T. C. F.; Nogueira, M. S.

    2016-02-01

    Mammography is the main radiographic technique used for breast imaging. A major concern with mammographic imaging is the risk of radiation-induced breast cancer due to the high sensitivity of breast tissue. The mean glandular dose (DG) is the dosimetric quantity widely accepted to characterize the risk of radiation induced cancer. Previous studies have concluded that DG depends not only on the breast glandular content but also on the spatial distribution of glandular tissue within the breast. In this work, a new method for generating computational breast models featuring skin composition and glandular tissue distribution from patients undergoing digital mammography is proposed. Such models allow a more accurate way of calculating individualized breast glandular doses taking into consideration the glandular tissue fraction. Sixteen breast models of four patients with different glandularity breasts were simulated and the results were compared with those obtained from recommended DG conversion factors. The results show that the internationally recommended conversion factors may be overestimating the mean glandular dose to less dense breasts and underestimating the mean glandular dose for denser breasts. The methodology described in this work constitutes a powerful tool for breast dosimetry, especially for risk studies.

  5. Deep tissue volume imaging of birefringence through fibre-optic needle probes for the delineation of breast tumour

    NASA Astrophysics Data System (ADS)

    Villiger, Martin; Lorenser, Dirk; McLaughlin, Robert A.; Quirk, Bryden C.; Kirk, Rodney W.; Bouma, Brett E.; Sampson, David D.

    2016-07-01

    Identifying tumour margins during breast-conserving surgeries is a persistent challenge. We have previously developed miniature needle probes that could enable intraoperative volume imaging with optical coherence tomography. In many situations, however, scattering contrast alone is insufficient to clearly identify and delineate malignant regions. Additional polarization-sensitive measurements provide the means to assess birefringence, which is elevated in oriented collagen fibres and may offer an intrinsic biomarker to differentiate tumour from benign tissue. Here, we performed polarization-sensitive optical coherence tomography through miniature imaging needles and developed an algorithm to efficiently reconstruct images of the depth-resolved tissue birefringence free of artefacts. First ex vivo imaging of breast tumour samples revealed excellent contrast between lowly birefringent malignant regions, and stromal tissue, which is rich in oriented collagen and exhibits higher birefringence, as confirmed with co-located histology. The ability to clearly differentiate between tumour and uninvolved stroma based on intrinsic contrast could prove decisive for the intraoperative assessment of tumour margins.

  6. Deep tissue volume imaging of birefringence through fibre-optic needle probes for the delineation of breast tumour.

    PubMed

    Villiger, Martin; Lorenser, Dirk; McLaughlin, Robert A; Quirk, Bryden C; Kirk, Rodney W; Bouma, Brett E; Sampson, David D

    2016-01-01

    Identifying tumour margins during breast-conserving surgeries is a persistent challenge. We have previously developed miniature needle probes that could enable intraoperative volume imaging with optical coherence tomography. In many situations, however, scattering contrast alone is insufficient to clearly identify and delineate malignant regions. Additional polarization-sensitive measurements provide the means to assess birefringence, which is elevated in oriented collagen fibres and may offer an intrinsic biomarker to differentiate tumour from benign tissue. Here, we performed polarization-sensitive optical coherence tomography through miniature imaging needles and developed an algorithm to efficiently reconstruct images of the depth-resolved tissue birefringence free of artefacts. First ex vivo imaging of breast tumour samples revealed excellent contrast between lowly birefringent malignant regions, and stromal tissue, which is rich in oriented collagen and exhibits higher birefringence, as confirmed with co-located histology. The ability to clearly differentiate between tumour and uninvolved stroma based on intrinsic contrast could prove decisive for the intraoperative assessment of tumour margins. PMID:27364229

  7. Deep tissue volume imaging of birefringence through fibre-optic needle probes for the delineation of breast tumour

    PubMed Central

    Villiger, Martin; Lorenser, Dirk; McLaughlin, Robert A.; Quirk, Bryden C.; Kirk, Rodney W.; Bouma, Brett E.; Sampson, David D.

    2016-01-01

    Identifying tumour margins during breast-conserving surgeries is a persistent challenge. We have previously developed miniature needle probes that could enable intraoperative volume imaging with optical coherence tomography. In many situations, however, scattering contrast alone is insufficient to clearly identify and delineate malignant regions. Additional polarization-sensitive measurements provide the means to assess birefringence, which is elevated in oriented collagen fibres and may offer an intrinsic biomarker to differentiate tumour from benign tissue. Here, we performed polarization-sensitive optical coherence tomography through miniature imaging needles and developed an algorithm to efficiently reconstruct images of the depth-resolved tissue birefringence free of artefacts. First ex vivo imaging of breast tumour samples revealed excellent contrast between lowly birefringent malignant regions, and stromal tissue, which is rich in oriented collagen and exhibits higher birefringence, as confirmed with co-located histology. The ability to clearly differentiate between tumour and uninvolved stroma based on intrinsic contrast could prove decisive for the intraoperative assessment of tumour margins. PMID:27364229

  8. Fungal Malignant Otitis Externa with Facial Nerve Palsy: Tissue Biopsy Aids Diagnosis

    PubMed Central

    Walton, Jenny

    2014-01-01

    Fungal malignant otitis externa (FMOE) is a serious and potentially life-threatening condition that is challenging to manage. Diagnosis is often delayed due to the low sensitivity of aural swabs and many antifungal drugs have significant side effects. We present a case of FMOE, where formal tissue sampling revealed the diagnosis and the patient was successfully treated with voriconazole, in addition to an up to date review of the current literature. We would recommend tissue biopsy of the external auditory canal in all patients with suspected FMOE in addition to routine microbiology swabs. PMID:24649388

  9. Diverse, Biologically Relevant, and Targetable Gene Rearrangements in Triple-Negative Breast Cancer and Other Malignancies.

    PubMed

    Shaver, Timothy M; Lehmann, Brian D; Beeler, J Scott; Li, Chung-I; Li, Zhu; Jin, Hailing; Stricker, Thomas P; Shyr, Yu; Pietenpol, Jennifer A

    2016-08-15

    Triple-negative breast cancer (TNBC) and other molecularly heterogeneous malignancies present a significant clinical challenge due to a lack of high-frequency "driver" alterations amenable to therapeutic intervention. These cancers often exhibit genomic instability, resulting in chromosomal rearrangements that affect the structure and expression of protein-coding genes. However, identification of these rearrangements remains technically challenging. Using a newly developed approach that quantitatively predicts gene rearrangements in tumor-derived genetic material, we identified and characterized a novel oncogenic fusion involving the MER proto-oncogene tyrosine kinase (MERTK) and discovered a clinical occurrence and cell line model of the targetable FGFR3-TACC3 fusion in TNBC. Expanding our analysis to other malignancies, we identified a diverse array of novel and known hybrid transcripts, including rearrangements between noncoding regions and clinically relevant genes such as ALK, CSF1R, and CD274/PD-L1 The over 1,000 genetic alterations we identified highlight the importance of considering noncoding gene rearrangement partners, and the targetable gene fusions identified in TNBC demonstrate the need to advance gene fusion detection for molecularly heterogeneous cancers. Cancer Res; 76(16); 4850-60. ©2016 AACR. PMID:27231203

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

    SciTech Connect

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

    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.

  11. Breast tissue segmentation from x-ray radiographs

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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. PMID:25131521

  13. Oestrogen (ER) and progestin receptors (PR) in mammary tissue of the female dog: different receptor profile in non-malignant and malignant states.

    PubMed Central

    Rutteman, G. R.; Misdorp, W.; Blankenstein, M. A.; van den Brom, W. E.

    1988-01-01

    Oestrogen (ER) and progestin receptors (PR) were measured in cytosols from histologically normal mammary tissues (n = 30), and in benign (n = 59) and malignant mammary lesions (n = 49) from female dogs. Receptor levels greater than or equal to 5 fmol mg-1 protein were considered positive. The presence of histologically normal mammary epithelium within specimens of primary tumours was noticed as a factor that may cause false-positive receptor results. Receptor levels in non-malignant tissues, and the receptor status of primary cancers did not vary significantly with regard to the phase of oestrous cycle (anoestrus/metoestrus) or the influence of exogenous progestins. ER- or PR-positivity was more frequent and levels of both receptors were higher in 'normal' tissues and in benign lesions than in primary cancers (P less than 0.001). ER and PR levels were higher in benign lesions of dogs also developing malignant mammary tumours than in benign lesions of dogs that did not (P less than 0.02 and P less than 0.05, respectively). Regional and distant cancer metastases were frequently receptor-negative. In some dogs heterogeneity of receptor status was found between different sites of the same cancer. These findings indicate that in non-malignant mammary tissues of adult female dogs expression of the genes encoding ER and PR is common. In malignant tumours this property may become lost, in particular in advanced states of disease. PMID:3219269

  14. Exposure to the polyester PET precursor—terephthalic acid induces and perpetuates DNA damage-harboring non-malignant human breast cells

    PubMed Central

    Luciani-Torres, Maria Gloria; Moore, Dan H.; Dairkee, Shanaz H.

    2015-01-01

    Identification of early perturbations induced in cells from non-cancerous breast tissue is critical for understanding possible breast cancer risk from chemical exposure. We have demonstrated previously that exposure to the ubiquitous xenoestrogens, bisphenol A (BPA) and methyl paraben, promotes the hallmarks of cancer in non-malignant human high-risk donor breast epithelial cells (HRBECs) isolated from several donors. Here we show that terephthalic acid (TPA), a major chemical precursor of polyethylene terephthalate (PET) containers used for the storage of food and beverages, increased the ERα: ERβ ratio in multiple HRBEC samples, suggesting an estrogenic effect. Although, like BPA and methyl paraben, TPA also promoted resistance to tamoxifen-induced apoptosis, unlike these chemicals instead of inducing an increased S-phase fraction, TPA treatment arrested cell proliferation. DNA-PK, ATM and members of the MRN complex, known to be involved in DNA damage sensor and effector proteins, were elevated indicating induction of DNA strand breaks. Early DNA damage checkpoint response, mediated through p53/p21, led to G1 arrest in TPA-exposed cells. Removal of TPA from the growth medium resulted in the rapid induction of BCL2, increasing the ratio of anti-: pro-apoptotic proteins, together with overexpression of Cyclin A/CDK2 proteins. Consequently, despite elevated p53pSer15 and H2AXpSer139, indicating sustained DNA damage, TPA exposed cells resumed robust growth rates seen prior to TPA exposure. The propensity for the perpetuation of DNA aberrations that activate DNA damage pathways in non-malignant breast cells justifies careful consideration of human exposure to TPA, particularly at vulnerable life stages. PMID:25411358

  15. The fractional viscoelastic response of human breast tissue cells

    NASA Astrophysics Data System (ADS)

    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.

  16. Value of tissue harmonic imaging (THI) and contrast harmonic imaging (CHI) in detection and characterisation of breast tumours

    PubMed Central

    Jung, E. M.; Jungius, K.-P.; Ertan, K.

    2006-01-01

    The purpose of this study was to investigate the extent to which tissue harmonic imaging (THI), speckle reduction imaging (SRI), spatial compounding (SC) and contrast can improve detection and differentiation of breast tumours. We examined 38 patients (14 benign, 24 malignant tumours) with different combinations of THI, SRI and SC. The effect on delineation, margin, tissue differentiation and posttumoral phenomena was evaluated with a three-point score. Additionally, 1oo not palpable tumours (diameters: 4–15 mm) were examined by contrast harmonic imaging (CHI) with power Doppler. After bolus injection (0.5 ml Optison), vascularisation and enhancement were observed for 20 min. The best combination for detection of margin, infiltration, echo pattern and posterior lesion boundary was the combination of SRI level 2 with SC low. THI was helpful for lesions OF more than 1 cm depth. In native Power Doppler, vessels were found in 54 of 100 lesions. Within 5 min after contrast medium (CM) injection, marginal and penetrating vessels increased in benign and malignant tumours and central vessels mostly in carcinomas (p<0.05). A diffuse CM accumulation was observed up to 20 min after injection in malignant tumours only (p<0.05). THI, SRI and SC improved delineation and tissue differentiation. Second-generation contrast agent allowed detection of tumour vascularisation with prolonged enhancement. PMID:16823568

  17. Anatomic and clinical rationale of the V-sign to detect accessory axillary breast tissue.

    PubMed

    Naraynsingh, Vijay; Cawich, Shamir O; Maharaj, Ravi; Dan, Dilip; Hassranah, Dale

    2014-01-01

    The potential for breast cancer to present with lymphatic metastases, has instilled anxiety when women present with axillary masses. We discuss a simple and reliable clinical sign that can help clinicians to distinguish between axillary nodal metastases and accessory axillary breast tissue. Awareness and recognition of the "V-sign" can allay anxiety in women with accessary axillary breast tissue and prevent costly investigations in most cases. PMID:24591849

  18. Optical characterization of normal, benign, and malignant thyroid tissue: a pilot study.

    PubMed

    Brandao, M P; Iwakura, R; Basilio, F S; Haleplian, K; Ito, A S; de Freitas, L C Conti; Bachmann, L

    2015-03-01

    Fine-needle aspiration cytology is the standard technique to diagnose thyroid pathologies. However, this method has a high percentage of inconclusive and false-negative results for benign and malignant lesions. Hence, it is important to search for a new method to assist medical evaluation during these surgical procedures. The use of time-resolved fluorescence techniques to detect biochemical composition and tissue structure alterations could help to develop a portable, minimally invasive, and non-destructive method to assist medical evaluation. In this study, we investigated 17 human thyroid samples by absorbance, fluorescence, excitation, and time-resolved fluorescence measurements. This initial investigation has demonstrated that thyroid fluorescence originates from many endogenous fluorophores and culminates in several bands. The fluorescence lifetimes of benign and malignant lesions were significantly different, as attested by analysis of variance using Tukey test with individual confidence level of 98.06%. Our results suggest that fluorescence lifetimes of benign and malignant lesions can potentially assist diagnosis. After further investigations, fluorescence methods could become a tool for the surgeon to identify differences between normal and pathological thyroid tissues. PMID:25731814

  19. Characterization of adipose-derived stem cells from subcutaneous and visceral adipose tissues and their function in breast cancer cells

    PubMed Central

    Ritter, Andreas; Friemel, Alexandra; Fornoff, Friderike; Adjan, Mouhib; Solbach, Christine

    2015-01-01

    Adipose-derived stem cells are capable of differentiating into multiple cell types and thus considered useful for regenerative medicine. However, this differentiation feature seems to be associated with tumor initiation and metastasis raising safety concerns, which requires further investigation. In this study, we isolated adipose-derived stem cells from subcutaneous as well as from visceral adipose tissues of the same donor and systematically compared their features. Although being characteristic of mesenchymal stem cells, subcutaneous adipose-derived stem cells tend to be spindle form-like and are more able to home to cancer cells, whereas visceral adipose-derived stem cells incline to be “epithelial”-like and more competent to differentiate. Moreover, compared to subcutaneous adipose-derived stem cells, visceral adipose-derived stem cells are more capable of promoting proliferation, inducing the epithelial-to-mesenchymal transition, enhancing migration and invasion of breast cancer cells by cell-cell contact and by secreting interleukins such as IL-6 and IL-8. Importantly, ASCs affect the low malignant breast cancer cells MCF-7 more than the highly metastatic MDA-MB-231 cells. Induction of the epithelial-to-mesenchymal transition is mediated by the activation of multiple pathways especially the PI3K/AKT signaling in breast cancer cells. BCL6, an important player in B-cell lymphoma and breast cancer progression, is crucial for this transition. Finally, this transition fuels malignant properties of breast cancer cells and render them resistant to ATP competitive Polo-like kinase 1 inhibitors BI 2535 and BI 6727. PMID:26439686

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

    SciTech Connect

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

    2002-08-20

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

  1. Irradiated HMEC from A-T Heterozygous Breast Tissue

    NASA Technical Reports Server (NTRS)

    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.

  2. Salvaging the Infected Breast Tissue Expander: A Standardized Multidisciplinary Approach

    PubMed Central

    Selber, Jesse C.; Crosby, Melissa; Raad, Issam I.; Butler, Charles E.; Villa, Mark T.; Kronowitz, Steven J.; Clemens, Mark W.; Garvey, Patrick; Yang, Wei; Baumann, Donald P.

    2016-01-01

    Background: Infections of breast tissue expander (TE) are complex, often requiring TE removal and hospitalization, which can delay further adjuvant therapy and add to the overall costs of breast reconstruction. Therefore, to reduce the rate of TE removal, hospitalization, and costs, we created a standardized same-day multidisciplinary outpatient quality improvement protocol for diagnosing and treating patients with early signs of TE infection. Methods: We prospectively evaluated 26 consecutive patients who developed a surgical site infection between February 2013 and April 2014. On the same day, patients were seen in the Plastic Surgery and Infectious Diseases clinics, underwent breast ultrasonography with or without periprosthetic fluid aspiration, and were prescribed a standardized empiric oral or intravenous antimicrobial regimen active against biofilm-embedded microorganisms. All patients were managed as per our established treatment algorithm and were followed up for a minimum of 1 year. Results: TEs were salvaged in 19 of 26 patients (73%). Compared with TE-salvaged patients, TE-explanted patients had a shorter median time to infection (20 vs 40 days; P = 0.09), a significantly higher median temperature at initial presentation [99.8°F; interquartile range (IQR) = 2.1 vs 98.3°F; IQR = 0.4°F; P = 0.01], and a significantly longer median antimicrobial treatment duration (28 days; IQR = 27 vs 21 days; IQR = 14 days; P = 0.05). The TE salvage rates of patients whose specimen cultures yielded no microbial growth, Staphylococcus species, and Pseudomonas were 92%, 75%, and 0%, respectively. Patients who had developed a deep-seated pocket infection were significantly more likely than those with superficial cellulitis to undergo TE explantation (P = 0.021). Conclusions: Our same-day multidisciplinary diagnostic and treatment algorithm not only yielded a TE salvage rate higher than those previously reported but also decreased the rate of hospitalization, decreased

  3. Image Segmentation and Identification of Paired Antibodies in Breast Tissue

    PubMed Central

    Azar, Jimmy C.; Simonsson, Martin

    2014-01-01

    Comparing staining patterns of paired antibodies designed towards a specific protein but toward different epitopes of the protein provides quality control over the binding and the antibodies' ability to identify the target protein correctly and exclusively. We present a method for automated quantification of immunostaining patterns for antibodies in breast tissue using the Human Protein Atlas database. In such tissue, dark brown dye 3,3′-diaminobenzidine is used as an antibody-specific stain whereas the blue dye hematoxylin is used as a counterstain. The proposed method is based on clustering and relative scaling of features following principal component analysis. Our method is able (1) to accurately segment and identify staining patterns and quantify the amount of staining and (2) to detect paired antibodies by correlating the segmentation results among different cases. Moreover, the method is simple, operating in a low-dimensional feature space, and computationally efficient which makes it suitable for high-throughput processing of tissue microarrays. PMID:25061472

  4. Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche1

    PubMed Central

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

    2015-01-01

    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. PMID:26696367

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

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

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

  6. Fluorescence imaging of premalignant and malignant tissues with and without photosensitizers

    NASA Astrophysics Data System (ADS)

    Lam, Stephen; MacAulay, Calum E.; Le Riche, Jean C.; Qu, Jianan Y.; Krosl, Gorazd; Zeng, Haishan; Korbelik, Mladen; Palcic, Branko

    1993-06-01

    A fluorescence imaging device exploiting differences in tissue autofluorescence between pre- malignant, malignant and normal tissues was developed to detect and clearly delineate the exact location and extent of these lesions. The device consists of a Helium-Cadmium laser (442 nm) for illumination and two image-intensifies CCD cameras with a red and green filter to capture a red and green fluorescence image simultaneously onto an imaging board of a computer. A pseudo-image is then computed and displayed in real time. In patients with known or suspected lung cancer, dysplastic lesions and carcinoma in-situ were localized that would otherwise escape detection by conventional white-light bronchoscopy. The extent of endobronchial spread of tumor can be accurately determined, which is important for successful application of photodynamic therapy for early lung cancer. The same device can also be used to study the uptake and distribution of fluorescent antineoplastic agents such as Taxol and Doxorubicin. Preliminary studies in mice bearing SCCVII squamous sell carcinoma suggest preferential retention of Taxol in tumor tissues 4 to 44 hours after intravenous injection.

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

    NASA Astrophysics Data System (ADS)

    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

  8. Feature Extraction and Analysis of Breast Cancer Specimen

    NASA Astrophysics Data System (ADS)

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

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

  9. Resonant Spectra of Malignant Breast Cancer Tumors Using the Three-Dimensional Electromagnetic Fast Multipole Model. Part 1

    NASA Technical Reports Server (NTRS)

    El-Shenawee, Magda

    2003-01-01

    An intensive numerical study for the resonance scattering of malignant breast cancer tumors is presented. The rigorous three-dimensional electromagnetic model, based on the equivalence theorem, is used to obtain the induced electric and magnetic currents on the breast and tumor surfaces. The results show that a non-spherical malignant tumor can be characterized based its spectra regardless of its orientation, the incident polarization, or the incident or scattered directions. The tumor's spectra depend solely on its physical characteristics (i.e., the shape and the electrical properties), however, their locations are not functions of its burial depth. This work provides a useful guidance to select the appropriate frequency range for the tumor's size.

  10. Hyperbaric oxygen therapy for late radiation tissue injury in gynecologic malignancies

    PubMed Central

    Craighead, P.; Shea–Budgell, M.A.; Nation, J.; Esmail, R.; Evans, A.W.; Parliament, M.; Oliver, T.K.; Hagen, N.A.

    2011-01-01

    Background Late radiation tissue injury is a serious complication of radiotherapy for patients with gynecologic malignancies. Strategies for managing pain and other clinical features have limited efficacy; however, hyperbaric oxygen therapy (HBO2) may be an effective option for some patients. Methods In a systematic review of the literature, the Ovid medline, embase, Cochrane Library, National Guidelines Clearinghouse, and Canadian Medical Association Infobase databases were searched to June 2009 for clinical practice guidelines, systematic reviews, randomized controlled trials, or other relevant evidence. Studies that did not evaluate soft tissue necrosis, cystitis, proctitis, bone necrosis, and other complications were excluded. Results Two randomized trials, eleven nonrandomized studies, and five supporting documents comprise the evidence base. In addition, information on the harms and safety of treatment with HBO2 were reported in three additional sources. There is modest direct evidence and emerging indirect evidence that the use of HBO2 is broadly effective for late radiation tissue injury of the pelvis in women treated for gynecologic malignancies. Conclusions Based on the evidence and expert consensus opinion, HBO2 is likely effective for late radiation tissue injury of the pelvis, with demonstrated efficacy specifically for radiation damage to the anus and rectum;the main indication for HBO2 therapy in gynecologic oncology is in the management of otherwise refractory chronic radiation injury;HBO2 may provide symptomatic benefit in certain clinical settings (for example, cystitis, soft-tissue necrosis, and osteonecrosis); andHBO2 may reduce the complications of gynecologic surgery in patients undergoing surgical removal of necrosis. PMID:21980249

  11. Pseudoangiomatous stromal hyperplasia (PASH) of the breast with foci of morphologic malignancy: a case of PASH with malignant transformation?

    PubMed

    Nassar, Hind; Elieff, Michelle P; Kronz, Joseph D; Argani, Pedram

    2010-12-01

    Pseudoangiomatous stromal hyperplasia (PASH) is a benign proliferation of the hormonally responsive, specialized mammary stroma characterized by slit-like pseudovascular spaces lined by bland spindle cells. It is usually an incidental microscopic finding but in some cases it may present as a slowly growing mass. A malignant counterpart for this lesion has not been reported. We describe a case of PASH with foci of malignant histologic features presenting as a slowly growing mass in a 30-year-old woman. The previously reported variants of PASH and the other mammary stromal lesions related to PASH are also discussed. This is perhaps the first case of PASH with foci of malignant histologic features reported in the literature and represents a rare sarcoma derived from specialized hormonally responsive mammary stroma. PMID:18611932

  12. Expression of WTH3 in breast cancer tissue and the effects on the biological behavior of breast cancer cells

    PubMed Central

    GAN, LIN; ZUO, GUOQING; WANG, TING; MIN, JIE; WANG, YADONG; WANG, YONGYUE; LV, GANG

    2015-01-01

    The aim of the present study was to investigate the expression of WTH3 in tumor and normal breast tissue. The mRNA and protein expression levels of WTH3 were detected using reverse transcription quantitative polymerase chain reaction and western blot analysis, respectively. In addition, matrix metalloproteinase (MMP)-2 protein expression was measured. The effect of WTH3 expression on the proliferation activity of breast cancer cells was detected using a Cell Counting Kit-8 assay. Furthermore, the effects of WTH3 on the invasion and migration ability of the breast cancer cells was investigated. The results revealed that WTH3 was able to significantly inhibit the proliferation of the MCF-7 and MDA-MB-231 breast cancer cell lines. In addition, the invasion and migration assay demonstrated that WTH3 was able to inhibit the invasion and migration of breast cancer cells. Western blot analysis revealed that increased expression of WTH3 resulted in decreased expression levels of MMP-2, which has an important function in the metastasis of cancer cells. In conclusion, WTH3 expression differed between the tumor and normal breast tissues. WTH3 was able to inhibit the proliferation of breast cancer cells and decrease their invasion ability. Thus, WTH3 may be a promising target for breast cancer therapy in the future. PMID:26170927

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

    PubMed

    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). PMID:22237600

  14. Activated FXR Inhibits Leptin Signaling and Counteracts Tumor-promoting Activities of Cancer-Associated Fibroblasts in Breast Malignancy

    PubMed Central

    Giordano, Cinzia; Barone, Ines; Vircillo, Valentina; Panza, Salvatore; Malivindi, Rocco; Gelsomino, Luca; Pellegrino, Michele; Rago, Vittoria; Mauro, Loredana; Lanzino, Marilena; Panno, Maria Luisa; Bonofiglio, Daniela; Catalano, Stefania; Andò, Sebastiano

    2016-01-01

    Cancer-associated fibroblasts (CAFs), the principal components of the tumor stroma, play a central role in cancer development and progression. As an important regulator of the crosstalk between breast cancer cells and CAFs, the cytokine leptin has been associated to breast carcinogenesis. The nuclear Farnesoid X Receptor-(FXR) seems to exert an oncosuppressive role in different tumors, including breast cancer. Herein, we demonstrated, for the first time, that the synthetic FXR agonist GW4064, inhibiting leptin signaling, affects the tumor-promoting activities of CAFs in breast malignancy. GW4064 inhibited growth, motility and invasiveness induced by leptin as well as by CAF-conditioned media in different breast cancer cell lines. These effects rely on the ability of activated FXR to increase the expression of the suppressor of the cytokine signaling 3 (SOCS3) leading to inhibition of leptin-activated signaling and downregulation of leptin-target genes. In vivo xenograft studies, using MCF-7 cells alone or co-injected with CAFs, showed that GW4064 administration markedly reduced tumor growth. Interestingly, GW4064-treated tumors exhibited decreased levels of leptin-regulated proteins along with a strong staining intensity for SOCS3. Thus, FXR ligands might represent an emerging potential anti-cancer therapy able to block the tumor supportive role of activated fibroblasts within the breast microenvironment. PMID:26899873

  15. Activated FXR Inhibits Leptin Signaling and Counteracts Tumor-promoting Activities of Cancer-Associated Fibroblasts in Breast Malignancy.

    PubMed

    Giordano, Cinzia; Barone, Ines; Vircillo, Valentina; Panza, Salvatore; Malivindi, Rocco; Gelsomino, Luca; Pellegrino, Michele; Rago, Vittoria; Mauro, Loredana; Lanzino, Marilena; Panno, Maria Luisa; Bonofiglio, Daniela; Catalano, Stefania; Andò, Sebastiano

    2016-01-01

    Cancer-associated fibroblasts (CAFs), the principal components of the tumor stroma, play a central role in cancer development and progression. As an important regulator of the crosstalk between breast cancer cells and CAFs, the cytokine leptin has been associated to breast carcinogenesis. The nuclear Farnesoid X Receptor-(FXR) seems to exert an oncosuppressive role in different tumors, including breast cancer. Herein, we demonstrated, for the first time, that the synthetic FXR agonist GW4064, inhibiting leptin signaling, affects the tumor-promoting activities of CAFs in breast malignancy. GW4064 inhibited growth, motility and invasiveness induced by leptin as well as by CAF-conditioned media in different breast cancer cell lines. These effects rely on the ability of activated FXR to increase the expression of the suppressor of the cytokine signaling 3 (SOCS3) leading to inhibition of leptin-activated signaling and downregulation of leptin-target genes. In vivo xenograft studies, using MCF-7 cells alone or co-injected with CAFs, showed that GW4064 administration markedly reduced tumor growth. Interestingly, GW4064-treated tumors exhibited decreased levels of leptin-regulated proteins along with a strong staining intensity for SOCS3. Thus, FXR ligands might represent an emerging potential anti-cancer therapy able to block the tumor supportive role of activated fibroblasts within the breast microenvironment. PMID:26899873

  16. Novel tissue mimicking materials for high frequency breast ultrasound phantoms.

    PubMed

    Cannon, Louise M; Fagan, Andrew J; Browne, Jacinta E

    2011-01-01

    The development and acoustical characterisation of a range of novel agar-based tissue mimicking material (TMMs) for use in clinically relevant, quality assurance (QA) and anthropomorphic breast phantoms are presented. The novel agar-based TMMs described in this study are based on a comprehensive, systematic variation of the ingredients in the International Electrotechnical Commission (IEC) TMM. A novel, solid fat-mimicking material was also developed and acoustically characterised. Acoustical characterisation was carried out using an in-house scanning acoustic macroscope at low (7.5 MHz) and high frequencies (20 MHz), using the pulse-echo insertion technique. The speeds of sound range from 1490 to 1570 m. s(-1), attenuation coefficients range from 0.1 to 0.9 dB. cm(‑1). MHz(-1) and relative backscatter ranges from 0 to -20 dB. It was determined that tissues can be mimicked in terms of independently controllable speeds of sound and attenuation coefficients. These properties make these novel TMMs suitable for use in clinically relevant QA and anthropomorphic phantoms and would potentially be useful for other high frequency applications such as intravascular and small animal imaging. PMID:21084158

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

    PubMed

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

    2016-09-01

    p53 alterations have been identified in approximately 23% of breast carcinomas, particularly in hormone receptor-negative high-grade carcinomas. It is considered to be an early event in breast carcinogenesis. Nevertheless, the putative precursor lesion of high-grade breast carcinoma remains elusive. Breast excision specimens from 93 triple-negative high-grade invasive ductal carcinomas, 48 estrogen receptor (ER)-positive/progesterone receptor-positive/Her2-negative non-high-grade invasive ductal carcinomas, and 50 mammoplasty breasts were selected. At least 2 tissue blocks with tumor and adjacent benign tissue were sectioned and subjected to immunohistochemistry staining for p53. TP53 gene sequencing was performed on select tumors. Further immunohistochemistry staining for ER and Ki-67 was performed on consecutive sections of tissue with p53-positive normal/benign cells. Of the 93 high-grade carcinomas, 51 (55%) were positive for p53 alteration, whereas only 3 (6.25%) of the 48 non-high-grade carcinomas were p53 altered. Focal p53 positivity in adjacent normal/benign breast tissue was identified in 19 cases, and 18 of them also had p53 alteration in their carcinomas. Only 1 case had focal p53 staining in normal/benign tissue, but the tumor was negative for p53 alteration. No p53 staining positivity was identified in the mammoplasty specimens. The p53-stained normal/benign cells were ER negative and did not show an increase in the Ki-67 labeling index. These findings indicate that the p53 staining positivity in normal/benign breast tissue is not a random event. It could be considered as the "p53 signature" in breast and serve as an indicator for future potential risk of p53-positive high-grade breast carcinoma. PMID:27246177

  18. Photoacoustic spectroscopy of ovarian normal, benign, and malignant tissues: a pilot study

    NASA Astrophysics Data System (ADS)

    Kamath, Sudha D.; Ray, Satadru; Mahato, Krishna K.

    2011-06-01

    Photoacoustic spectra of normal, benign, and malignant ovarian tissues are recorded using 325-nm pulsed laser excitation in vitro. A total of 102 (34 normal, 38 benign, and 30 malignant) spectra are obtained from 22 samples belonging to normal, benign, and malignant subjects. Applying multi-algorithm approach, comprised of methods such as, principal component analysis (PCA) based k-nearest neighbor (k-NN) analysis, artificial neural network (ANN) analysis, and support vector machine (SVM) analysis, classification of the data has been carried out. For PCA, first the calibration set is formed by pooling 45 spectra, 15 belonging to each of pathologically certified normal, benign, and malignant samples. PCA is then performed on the data matrix, comprised of the six spectral features extracted from each of 45 calibration samples, and three principal components (PCs) containing maximum diagnostic information are selected. The scores of the selected PCs are used to train the k-NN, ANN, and SVM classifiers. The ANN used is a classical multilayer feed forward network with back propagation algorithm for its training. For k-NN, the Euclidean distance based algorithm is used and for SVM, one-versus-rest multiclass kernel-radial basis function is used. The performance evaluation of the classification results are obtained by calculating statistical parameters like specificity and sensitivity. ANN and k-NN techniques showed identical performance with specificity and sensitivity values of 100 and 86.76%, whereas SVM had these values at 100 and 80.18%, respectively. In order to determine the relative diagnostic performance of the techniques, receiver operating characteristics analysis is also performed.

  19. Leptospira in breast tissue and milk of urban Norway rats (Rattus norvegicus).

    PubMed

    DE Oliveira, D; Figueira, C P; Zhan, L; Pertile, A C; Pedra, G G; Gusmão, I M; Wunder, E A; Rodrigues, G; Ramos, E A G; Ko, A I; Childs, J E; Reis, M G; Costa, F

    2016-08-01

    Leptospirosis is a zoonosis caused by bacteria of the genus Leptospira. The disease is globally distributed and a major public health concern. The Norway rat (Rattus norvegicus) is the main reservoir of the pathogen in urban slums of developing and developed countries. The potential routes of intra-specific leptospire transmission in rats are largely unknown. Herein, we identified pathogenic Leptospira spp. in breast tissue and milk of naturally infected rats. We examined kidney, breast tissue and milk from 24 lactating rats for the presence of leptospires using immunofluorescence, immunohistochemistry, polymerase chain reaction (PCR) and scanning electronic microscopy. All 24 rats had evidence for Leptospira in the kidneys, indicating chronic carriage. The majority of kidney-positive rats had detectable leptospires in milk (18, 75%) and breast tissue (16, 67%), as evidenced by immunofluorescence assay and immunohistochemistry. Four (17%) milk samples and two (8%) breast tissue samples were positive by quantitative real-time PCR. Scanning electron microscopy confirmed the presence of leptospires in breast tissue. No major pathological changes in breast tissue were found. This study, for the first time, identified leptospires in the milk and breast tissue of wild Norway rats, suggesting the possibility of milk-borne transmission of leptospirosis to neonates. PMID:27019024

  20. Estimation of effective x-ray tissue attenuation differences for volumetric breast density measurement

    NASA Astrophysics Data System (ADS)

    Chen, Biao; Ruth, Chris; Jing, Zhenxue; Ren, Baorui; Smith, Andrew; Kshirsagar, Ashwini

    2014-03-01

    Breast density has been identified to be a risk factor of developing breast cancer and an indicator of lesion diagnostic obstruction due to masking effect. Volumetric density measurement evaluates fibro-glandular volume, breast volume, and breast volume density measures that have potential advantages over area density measurement in risk assessment. One class of volume density computing methods is based on the finding of the relative fibro-glandular tissue attenuation with regards to the reference fat tissue, and the estimation of the effective x-ray tissue attenuation differences between the fibro-glandular and fat tissue is key to volumetric breast density computing. We have modeled the effective attenuation difference as a function of actual x-ray skin entrance spectrum, breast thickness, fibro-glandular tissue thickness distribution, and detector efficiency. Compared to other approaches, our method has threefold advantages: (1) avoids the system calibration-based creation of effective attenuation differences which may introduce tedious calibrations for each imaging system and may not reflect the spectrum change and scatter induced overestimation or underestimation of breast density; (2) obtains the system specific separate and differential attenuation values of fibroglandular and fat for each mammographic image; and (3) further reduces the impact of breast thickness accuracy to volumetric breast density. A quantitative breast volume phantom with a set of equivalent fibro-glandular thicknesses has been used to evaluate the volume breast density measurement with the proposed method. The experimental results have shown that the method has significantly improved the accuracy of estimating breast density.

  1. CD24 suppresses malignant phenotype by downregulation of SHH transcription through STAT1 inhibition in breast cancer cells.

    PubMed

    Suyama, Kumi; Onishi, Hideya; Imaizumi, Akira; Shinkai, Kentaro; Umebayashi, Masayo; Kubo, Makoto; Mizuuchi, Yusuke; Oda, Yoshinao; Tanaka, Masao; Nakamura, Masafumi; Katano, Mitsuo

    2016-04-28

    Hedgehog (Hh) signaling has been found to be activated in breast cancer stem cells (BCSCs). However, the precise role of the BCSCs marker, CD24, remains unclear. Here, we describe a relationship between CD24 and Sonic Hedgehog (SHH), and reveal a role for this relationship in the induction of a malignant phenotype of breast cancer. CD24 siRNA-transfected breast cancer cells (BCCs) demonstrated higher expression of SHH and GLI1, increased anchorage-independent proliferation, and enhanced invasiveness and superior tumorigenicity compared with control. Conversely, CD24 forced-expressing BCCs possessed decreased SHH and GLI1 expression, anchorage-independent proliferation, and invasiveness. Suppression of SHH decreased invasiveness through inhibition of matrix metalloproteinase (MMP)-2 expression, GLI1 expression, anchorage-independent proliferation, tumorigenicity, and tumor volume in vivo in CD24 siRNA transfected BCCs. DNA microarray analysis identified STAT1 as a relationship between CD24 and SHH. CD24 siRNA-transfected BCCs with concurrent STAT1 inhibition exhibited decreased SHH expression, invasiveness, anchorage-independent proliferation, tumorigenicity, and tumor volume in vivo. These results suggest that CD24 suppresses development of a malignant phenotype by down-regulating SHH transcription through STAT1 inhibition. CD24 gene transfer or STAT1 inhibition may represent new effective therapeutic strategies to target refractory breast cancer. PMID:26797459

  2. Optical spectroscopy for quantification of bulk breast tissue properties in adolescent girls: preliminary observations

    NASA Astrophysics Data System (ADS)

    Dick, Samantha N.; Lilge, Lothar

    2005-09-01

    Optical technology holds considerable promise to improve early detection, diagnosis and risk assessment of breast cancer. Unlike current clinical risk assessment tools such as the Gail model, the most widely accepted risk assessment tool, optical risk assessment technology can be applied to the entire female population of all ages. This study is investigating the use of optical reflectance spectroscopy (ORS) as a possible breast tissue development monitoring tool for adolescent girls. Changes in breast development due to proliferation of mammary gland and the surrounding stroma are reflected in changes in breast tissue density and composition which can be interrogated optically. Modifications of development influenced by micronutrients and hormonal status from exposures (e.g. toxins), lifestyle and diet effects, may ultimately be tracked. Preliminary data suggests that ORS has the ability to detect differences in bulk tissue properties in the developing breast of adolescent girls when compared to developmental stages assessed by Tanner, regional variation within breast tissue structure and asymmetries between left and right breast size and shape. Spectral comparison of unilateral breast development permits adjusting the optode separation as function of developmental breast size to minimize optical sampling of pectoral muscle.

  3. Novel ZnO hollow-nanocarriers containing paclitaxel targeting folate-receptors in a malignant pH-microenvironment for effective monitoring and promoting breast tumor regression

    PubMed Central

    Puvvada, Nagaprasad; Rajput, Shashi; Kumar, B.N. Prashanth; Sarkar, Siddik; Konar, Suraj; Brunt, Keith R.; Rao, Raj R.; Mazumdar, Abhijit; Das, Swadesh K.; Basu, Ranadhir; Fisher, Paul B.; Mandal, Mahitosh; Pathak, Amita

    2015-01-01

    Low pH in the tumor micromilieu is a recognized pathological feature of cancer. This attribute of cancerous cells has been targeted herein for the controlled release of chemotherapeutics at the tumour site, while sparing healthy tissues. To this end, pH-sensitive, hollow ZnO-nanocarriers loaded with paclitaxel were synthesized and their efficacy studied in breast cancer in vitro and in vivo. The nanocarriers were surface functionalized with folate using click-chemistry to improve targeted uptake by the malignant cells that over-express folate-receptors. The nanocarriers released ~75% of the paclitaxel payload within six hours in acidic pH, which was accompanied by switching of fluorescence from blue to green and a 10-fold increase in the fluorescence intensity. The fluorescence-switching phenomenon is due to structural collapse of the nanocarriers in the endolysosome. Energy dispersion X-ray mapping and whole animal fluorescent imaging studies were carried out to show that combined pH and folate-receptor targeting reduces off-target accumulation of the nanocarriers. Further, a dual cell-specific and pH-sensitive nanocarrier greatly improved the efficacy of paclitaxel to regress subcutaneous tumors in vivo. These nanocarriers could improve chemotherapy tolerance and increase anti-tumor efficacy, while also providing a novel diagnostic read-out through fluorescent switching that is proportional to drug release in malignant tissues. PMID:26145450

  4. Novel ZnO hollow-nanocarriers containing paclitaxel targeting folate-receptors in a malignant pH-microenvironment for effective monitoring and promoting breast tumor regression.

    PubMed

    Puvvada, Nagaprasad; Rajput, Shashi; Kumar, B N Prashanth; Sarkar, Siddik; Konar, Suraj; Brunt, Keith R; Rao, Raj R; Mazumdar, Abhijit; Das, Swadesh K; Basu, Ranadhir; Fisher, Paul B; Mandal, Mahitosh; Pathak, Amita

    2015-01-01

    Low pH in the tumor micromilieu is a recognized pathological feature of cancer. This attribute of cancerous cells has been targeted herein for the controlled release of chemotherapeutics at the tumour site, while sparing healthy tissues. To this end, pH-sensitive, hollow ZnO-nanocarriers loaded with paclitaxel were synthesized and their efficacy studied in breast cancer in vitro and in vivo. The nanocarriers were surface functionalized with folate using click-chemistry to improve targeted uptake by the malignant cells that over-express folate-receptors. The nanocarriers released ~75% of the paclitaxel payload within six hours in acidic pH, which was accompanied by switching of fluorescence from blue to green and a 10-fold increase in the fluorescence intensity. The fluorescence-switching phenomenon is due to structural collapse of the nanocarriers in the endolysosome. Energy dispersion X-ray mapping and whole animal fluorescent imaging studies were carried out to show that combined pH and folate-receptor targeting reduces off-target accumulation of the nanocarriers. Further, a dual cell-specific and pH-sensitive nanocarrier greatly improved the efficacy of paclitaxel to regress subcutaneous tumors in vivo. These nanocarriers could improve chemotherapy tolerance and increase anti-tumor efficacy, while also providing a novel diagnostic read-out through fluorescent switching that is proportional to drug release in malignant tissues. PMID:26145450

  5. Novel ZnO hollow-nanocarriers containing paclitaxel targeting folate-receptors in a malignant pH-microenvironment for effective monitoring and promoting breast tumor regression

    NASA Astrophysics Data System (ADS)

    Puvvada, Nagaprasad; Rajput, Shashi; Kumar, B. N. Prashanth; Sarkar, Siddik; Konar, Suraj; Brunt, Keith R.; Rao, Raj R.; Mazumdar, Abhijit; Das, Swadesh K.; Basu, Ranadhir; Fisher, Paul B.; Mandal, Mahitosh; Pathak, Amita

    2015-07-01

    Low pH in the tumor micromilieu is a recognized pathological feature of cancer. This attribute of cancerous cells has been targeted herein for the controlled release of chemotherapeutics at the tumour site, while sparing healthy tissues. To this end, pH-sensitive, hollow ZnO-nanocarriers loaded with paclitaxel were synthesized and their efficacy studied in breast cancer in vitro and in vivo. The nanocarriers were surface functionalized with folate using click-chemistry to improve targeted uptake by the malignant cells that over-express folate-receptors. The nanocarriers released ~75% of the paclitaxel payload within six hours in acidic pH, which was accompanied by switching of fluorescence from blue to green and a 10-fold increase in the fluorescence intensity. The fluorescence-switching phenomenon is due to structural collapse of the nanocarriers in the endolysosome. Energy dispersion X-ray mapping and whole animal fluorescent imaging studies were carried out to show that combined pH and folate-receptor targeting reduces off-target accumulation of the nanocarriers. Further, a dual cell-specific and pH-sensitive nanocarrier greatly improved the efficacy of paclitaxel to regress subcutaneous tumors in vivo. These nanocarriers could improve chemotherapy tolerance and increase anti-tumor efficacy, while also providing a novel diagnostic read-out through fluorescent switching that is proportional to drug release in malignant tissues.

  6. Addiction to MTH1 protein results in intense expression in human breast cancer tissue as measured by liquid chromatography-isotope-dilution tandem mass spectrometry.

    PubMed

    Coskun, Erdem; Jaruga, Pawel; Jemth, Ann-Sofie; Loseva, Olga; Scanlan, Leona D; Tona, Alessandro; Lowenthal, Mark S; Helleday, Thomas; Dizdaroglu, Miral

    2015-09-01

    MTH1 protein sanitizes the nucleotide pool so that oxidized 2'-deoxynucleoside triphosphates (dNTPs) cannot be used in DNA replication. Cancer cells require MTH1 to avoid incorporation of oxidized dNTPs into DNA that results in mutations and cell death. Inhibition of MTH1 eradicates cancer, validating MTH1 as an anticancer target. By overexpressing MTH1, cancer cells may mediate cancer growth and resist therapy. To date, there is unreliable evidence suggesting that MTH1 is increased in cancer cells, and available methods to measure MTH1 levels are indirect and semi-quantitative. Accurate measurement of MTH1 in disease-free tissues and malignant tumors of patients may be essential for determining if the protein is truly upregulated in cancers, and for the development and use of MTH1 inhibitors in cancer therapy. Here, we present a novel approach involving liquid chromatography-isotope-dilution tandem mass spectrometry to positively identify and accurately quantify MTH1 in human tissues. We produced full length (15)N-labeled MTH1 and used it as an internal standard for the measurements. Following trypsin digestion, seven tryptic peptides of both MTH1 and (15)N-MTH1 were identified by their full scan and product ion spectra. These peptides provided a statistically significant protein score that would unequivocally identify MTH1. Next, we identified and quantified MTH1 in human disease-free breast tissues and malignant breast tumors, and in four human cultured cell lines, three of which were cancer cells. Extreme expression of MTH1 in malignant breast tumors was observed, suggesting that cancer cells are addicted to MTH1 for their survival. The approach described is expected to be applicable to the measurement of MTH1 levels in malignant tumors vs. surrounding disease-free tissues in cancer patients. This attribute may help develop novel treatment strategies and MTH1 inhibitors as potential drugs, and guide therapies. PMID:26202347

  7. Near-Infrared Spectroscopy as a Diagnostic Tool for Distinguishing between Normal and Malignant Colorectal Tissues

    PubMed Central

    Chen, Hui; Lin, Zan; Mo, Lin; Wu, Tong; Tan, Chao

    2015-01-01

    Cancer diagnosis is one of the most important tasks of biomedical research and has become the main objective of medical investigations. The present paper proposed an analytical strategy for distinguishing between normal and malignant colorectal tissues by combining the use of near-infrared (NIR) spectroscopy with chemometrics. The successive projection algorithm-linear discriminant analysis (SPA-LDA) was used to seek a reduced subset of variables/wavenumbers and build a diagnostic model of LDA. For comparison, the partial least squares-discriminant analysis (PLS-DA) based on full-spectrum classification was also used as the reference. Principal component analysis (PCA) was used for a preliminary analysis. A total of 186 spectra from 20 patients with partial colorectal resection were collected and divided into three subsets for training, optimizing, and testing the model. The results showed that, compared to PLS-DA, SPA-LDA provided more parsimonious model using only three wavenumbers/variables (4065, 4173, and 5758 cm−1) to achieve the sensitivity of 84.6%, 92.3%, and 92.3% for the training, validation, and test sets, respectively, and the specificity of 100% for each subset. It indicated that the combination of NIR spectroscopy and SPA-LDA algorithm can serve as a potential tool for distinguishing between normal and malignant colorectal tissues. PMID:25654106

  8. Characterization of the homogeneous tissue mixture approximation in breast imaging dosimetry

    SciTech Connect

    Sechopoulos, Ioannis; Bliznakova, Kristina; Qin Xulei; Fei Baowei; Feng, Steve Si Jia

    2012-08-15

    Purpose: To compare the estimate of normalized glandular dose in mammography and breast CT imaging obtained using the actual glandular tissue distribution in the breast to that obtained using the homogeneous tissue mixture approximation. Methods: Twenty volumetric images of patient breasts were acquired with a dedicated breast CT prototype system and the voxels in the breast CT images were automatically classified into skin, adipose, and glandular tissue. The breasts in the classified images underwent simulated mechanical compression to mimic the conditions present during mammographic acquisition. The compressed thickness for each breast was set to that achieved during each patient's last screening cranio-caudal (CC) acquisition. The volumetric glandular density of each breast was computed using both the compressed and uncompressed classified images, and additional images were created in which all voxels representing adipose and glandular tissue were replaced by a homogeneous mixture of these two tissues in a proportion corresponding to each breast's volumetric glandular density. All four breast images (compressed and uncompressed; heterogeneous and homogeneous tissue) were input into Monte Carlo simulations to estimate the normalized glandular dose during mammography (compressed breasts) and dedicated breast CT (uncompressed breasts). For the mammography simulations the x-ray spectra used was that used during each patient's last screening CC acquisition. For the breast CT simulations, two x-ray spectra were used, corresponding to the x-ray spectra with the lowest and highest energies currently being used in dedicated breast CT prototype systems under clinical investigation. The resulting normalized glandular dose for the heterogeneous and homogeneous versions of each breast for each modality was compared. Results: For mammography, the normalized glandular dose based on the homogeneous tissue approximation was, on average, 27% higher than that estimated using the

  9. Optimization of permanent breast seed implant dosimetry incorporating tissue heterogeneity

    NASA Astrophysics Data System (ADS)

    Mashouf, Shahram

    Seed brachytherapy is currently used for adjuvant radiotherapy of early stage prostate and breast cancer patients. The current standard for calculation of dose around brachytherapy sources is based on the AAPM TG43 formalism, which generates the dose in homogeneous water medium. Recently, AAPM task group no. 186 (TG186) emphasized the importance of accounting for heterogeneities. In this work we introduce an analytical dose calculation algorithm in heterogeneous media using CT images. The advantages over other methods are computational efficiency and the ease of integration into clinical use. An Inhomogeneity Correction Factor (ICF) is introduced as the ratio of absorbed dose in tissue to that in water medium. ICF is a function of tissue properties and independent of the source structure. The ICF is extracted using CT images and the absorbed dose in tissue can then be calculated by multiplying the dose as calculated by the TG43 formalism times ICF. To evaluate the methodology, we compared our results with Monte Carlo simulations as well as experiments in phantoms with known density and atomic compositions. The dose distributions obtained through applying ICF to TG43 protocol agreed very well with those of Monte Carlo simulations and experiments in all phantoms. In all cases, the mean relative error was reduced by at least a factor of two when ICF correction factor was applied to the TG43 protocol. In conclusion we have developed a new analytical dose calculation method, which enables personalized dose calculations in heterogeneous media using CT images. The methodology offers several advantages including the use of standard TG43 formalism, fast calculation time and extraction of the ICF parameters directly from Hounsfield Units. The methodology was implemented into our clinical treatment planning system where a cohort of 140 patients were processed to study the clinical benefits of a heterogeneity corrected dose.

  10. Diffusely scattered femtosecond white-light examination of breast tissue in vitro and in vivo

    NASA Astrophysics Data System (ADS)

    af Klinteberg, Claes; Berg, Roger; Lindquist, Charlotta; Andersson-Engels, Stefan; Svanberg, Sune

    1995-12-01

    Multispectral studies of light propagation in female breast tissue have been performed. Short pulses of white light were generated by using self-phase modulation of a high-power laser pulse focused into a cuvette filled with water. The white light pulses illuminated the tissue and the scattered light was recorded with time- and wavelength dispersion by a streak camera. Measurements were performed on breast mastectomies in vitro and measurements on healthy breast tissue in vivo. The reduced scattering coefficient and the absorption coefficient of breast tissue were obtained in different wavelength regions by fitting solutions of the diffusion equation to the experimental data. Significant variations in the magnitude of the optical properties could be seen between the different individuals. No characteristic spectral discrepancy for tumor tissue was found.

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

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

    PubMed

    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. PMID:26209254

  13. Variation in incidence of breast, lung and cervical cancer and malignant melanoma of skin by socioeconomic group in England

    PubMed Central

    Shack, Lorraine; Jordan, Catrina; Thomson, Catherine S; Mak, Vivian; Møller, Henrik

    2008-01-01

    Background Cancer incidence varies by socioeconomic group and these variations have been linked with environmental and lifestyle factors, differences in access to health care and health seeking behaviour. Socioeconomic variations in cancer incidence by region and age are less clearly understood but they are crucial for targeting prevention measures and health care commissioning. Methods Data were obtained from all eight English cancer registries for patients diagnosed between 1998 and 2003, for all invasive cases of female breast cancer (ICD-10 code C50), lung cancer (ICD-10 codes C33-C34), cervical cancer (ICD-10 code C53), and malignant melanoma of the skin (ICD-10 code C43). Socioeconomic status was assigned to each patient based on their postcode of residence at diagnosis, using the income domain of the Index of Multiple Deprivation 2004. We analysed the socioeconomic variations in the incidence of breast, lung and cervical cancer and malignant melanoma of the skin for England, and regionally and by age. Results Incidence was highest for the most deprived patients for lung cancer and cervical cancer, whilst the opposite was observed for malignant melanoma and breast cancer. The difference in incidence between the most and the least deprived groups was higher for lung cancer patients aged under 65 at diagnosis than those over 65 at diagnosis, which may indicate a cohort effect. There were regional differences in the socioeconomic gradients with the gap being widest for lung and cervical cancer in the North (North East, North West and Yorkshire and Humberside) and for malignant melanoma in the East and South West. There were only modest variations in breast cancer incidence by region. If the incidence of lung and cervical cancer were decreased to that of the least deprived group it would prevent 36% of lung cancer cases in men, 38% of lung cancer cases in women and 28% of cervical cancer cases. Incidence of breast cancer and melanoma was highest in the least

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

    PubMed Central

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

    2016-01-01

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

  15. A Three-dimensional Tissue Culture Model to Study Primary Human Bone Marrow and its Malignancies

    PubMed Central

    Parikh, Mukti R.; Belch, Andrew R.; Pilarski, Linda M; Kirshner, Julia

    2014-01-01

    Tissue culture has been an invaluable tool to study many aspects of cell function, from normal development to disease. Conventional cell culture methods rely on the ability of cells either to attach to a solid substratum of a tissue culture dish or to grow in suspension in liquid medium. Multiple immortal cell lines have been created and grown using such approaches, however, these methods frequently fail when primary cells need to be grown ex vivo. Such failure has been attributed to the absence of the appropriate extracellular matrix components of the tissue microenvironment from the standard systems where tissue culture plastic is used as a surface for cell growth. Extracellular matrix is an integral component of the tissue microenvironment and its presence is crucial for the maintenance of physiological functions such as cell polarization, survival, and proliferation. Here we present a 3-dimensional tissue culture method where primary bone marrow cells are grown in extracellular matrix formulated to recapitulate the microenvironment of the human bone (rBM system). Embedded in the extracellular matrix, cells are supplied with nutrients through the medium supplemented with human plasma, thus providing a comprehensive system where cell survival and proliferation can be sustained for up to 30 days while maintaining the cellular composition of the primary tissue. Using the rBM system we have successfully grown primary bone marrow cells from normal donors and patients with amyloidosis, and various hematological malignancies. The rBM system allows for direct, in-matrix real time visualization of the cell behavior and evaluation of preclinical efficacy of novel therapeutics. Moreover, cells can be isolated from the rBM and subsequently used for in vivo transplantation, cell sorting, flow cytometry, and nucleic acid and protein analysis. Taken together, the rBM method provides a reliable system for the growth of primary bone marrow cells under physiological conditions

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

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

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

  17. Ultrasound Shear Wave Simulation of Breast Tumor Using Nonlinear Tissue Elasticity.

    PubMed

    Park, Dae Woo

    2015-01-01

    Shear wave elasticity imaging (SWEI) can assess the elasticity of tissues, but the shear modulus estimated in SWEI is often less sensitive to a subtle change of the stiffness that produces only small mechanical contrast to the background tissues. Because most soft tissues exhibit mechanical nonlinearity that differs in tissue types, mechanical contrast can be enhanced if the tissues are compressed. In this study, a finite element- (FE-) based simulation was performed for a breast tissue model, which consists of a circular (D: 10 mm, hard) tumor and surrounding tissue (soft). The SWEI was performed with 0% to 30% compression of the breast tissue model. The shear modulus of the tumor exhibited noticeably high nonlinearity compared to soft background tissue above 10% overall applied compression. As a result, the elastic modulus contrast of the tumor to the surrounding tissue was increased from 0.46 at 0% compression to 1.45 at 30% compression. PMID:27293476

  18. Ultrasound Shear Wave Simulation of Breast Tumor Using Nonlinear Tissue Elasticity

    PubMed Central

    Park, Dae Woo

    2016-01-01

    Shear wave elasticity imaging (SWEI) can assess the elasticity of tissues, but the shear modulus estimated in SWEI is often less sensitive to a subtle change of the stiffness that produces only small mechanical contrast to the background tissues. Because most soft tissues exhibit mechanical nonlinearity that differs in tissue types, mechanical contrast can be enhanced if the tissues are compressed. In this study, a finite element- (FE-) based simulation was performed for a breast tissue model, which consists of a circular (D: 10 mm, hard) tumor and surrounding tissue (soft). The SWEI was performed with 0% to 30% compression of the breast tissue model. The shear modulus of the tumor exhibited noticeably high nonlinearity compared to soft background tissue above 10% overall applied compression. As a result, the elastic modulus contrast of the tumor to the surrounding tissue was increased from 0.46 at 0% compression to 1.45 at 30% compression. PMID:27293476

  19. 3D BREAST TISSUE CO-CULTURES FOR SCREENING MAMMARY CARCINOGENS - PHASE I

    EPA Science Inventory

    Breast cancer is not a disease of individual cells, but principally a failure of cells and tissues to communicate properly. One communication mechanism that is frequently disrupted in breast cancer involves the hormone estrogen. Despite recognition that exposure to compound...

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

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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. PMID:27376758

  3. DNA methylation outliers in normal breast tissue identify field defects that are enriched in cancer

    PubMed Central

    Teschendorff, Andrew E; Gao, Yang; Jones, Allison; Ruebner, Matthias; Beckmann, Matthias W.; Wachter, David L.; Fasching, Peter A.; Widschwendter, Martin

    2016-01-01

    Identifying molecular alterations in normal tissue adjacent to cancer is important for understanding cancer aetiology and designing preventive measures. Here we analyse the DNA methylome of 569 breast tissue samples, including 50 from cancer-free women and 84 from matched normal cancer pairs. We use statistical algorithms for dissecting intra- and inter-sample cellular heterogeneity and demonstrate that normal tissue adjacent to breast cancer is characterized by tens to thousands of epigenetic alterations. We show that their genomic distribution is non-random, being strongly enriched for binding sites of transcription factors specifying chromatin architecture. We validate the field defects in an independent cohort and demonstrate that over 30% of the alterations exhibit increased enrichment within matched cancer samples. Breast cancers highly enriched for epigenetic field defects, exhibit adverse clinical outcome. Our data support a model where clonal epigenetic reprogramming towards reduced differentiation in normal tissue is an important step in breast carcinogenesis. PMID:26823093

  4. Catalase ameliorates polychlorinated biphenyl-induced cytotoxicity in non-malignant human breast epithelial cells

    PubMed Central

    Venkatesha, Venkatasubbaiah A.; Venkataraman, Sujatha; Sarsour, Ehab H.; Kalen, Amanda L.; Buettner, Garry R.; Robertson, Larry W.; Lehmler, Hans-Joachim; Goswami, Prabhat C.

    2008-01-01

    Polychlorinated biphenyls (PCBs) are environmental chemical contaminants believed to adversely affect cellular processes. We investigated the hypothesis that PCB-induced changes in the levels of cellular reactive oxygen species (ROS) induce DNA damage resulting in cytotoxicity. Exponentially growing cultures of human non-malignant breast epithelial cells (MCF10A) were incubated with PCBs for 3 days and assayed for cell number, ROS levels, DNA damage, and cytotoxicity. Exposure to 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) or 2-(4-chlorophenyl)benzo-1,4-quinone (4-Cl-BQ), a metabolite of 4-chlorobiphenyl (PCB3) significantly decreased cell number, MTS reduction, and increased the percentage of cells with sub G1 DNA content. Results from electron paramagnetic resonance (EPR) spectroscopy showed a 4-fold increase in the steady-state levels of ROS, which was suppressed in cells pre-treated with catalase. EPR measurements in cells treated with 4-Cl-BQ detected the presence of a semiquinone radical, suggesting that the increased levels of ROS could be due to the redox-cycling of 4-Cl-BQ. A dose-dependent increase in micronuclei frequency was observed in PCB-treated cells, consistent with an increase in histone 2AX-phosphorylation. Treatment of cells with catalase blunted the PCB-induced increase in micronuclei frequency and H2AX phosphorylation that was consistent with an increase in cell survival. Our results demonstrate a PCB-induced increase in cellular levels of ROS causing DNA damage, resulting in cell killing. PMID:18691649

  5. Mammosphere formation assay from human breast cancer tissues and cell lines.

    PubMed

    Lombardo, Ylenia; de Giorgio, Alexander; Coombes, Charles R; Stebbing, Justin; Castellano, Leandro

    2015-01-01

    Similar to healthy tissues, many blood and solid malignancies are now thought to be organised hierarchically, with a subset of stem-like cancer cells that self-renew while giving rise to more differentiated progeny. Understanding and targeting these cancer stem cells in breast cancer, which may possess enhanced chemo- and radio-resistance compared to the non-stem tumor bulk, has become an important research area. Markers including CD44, CD24, and ALDH activity can be assessed using fluorescence activated cell sorting (FACS) to prospectively isolate cells that display enhanced tumorigenicity when implanted into immunocompromised mice: the mammosphere assay has also become widely used for its ability to retrospectively identify sphere-forming cells that develop from single stem cell-like clones. Here we outline approaches for the appropriate culturing of mammospheres from cell lines or primary patient samples, their passaging, and calculations to estimate sphere forming efficiency (SFE). First we discuss key considerations and pitfalls in the appropriate planning and interpretation of mammosphere experiments. PMID:25867607

  6. Arrowhead approach for malignancies in the lower hemisphere of the breast

    PubMed Central

    2016-01-01

    Breast conservation treatment (BCT) is the preferred modality of treatment for early breast cancer. However, a moderate proportion of women will develop deformity and those with tumours in the lower hemisphere of the breast pose a particular challenge. Here, a technique is described which allows acceptable cosmetic outcome in women with small or medium-sized breasts without the use of therapeutic mammoplasty or volume replacement with flaps. PMID:26855913

  7. Arrowhead approach for malignancies in the lower hemisphere of the breast.

    PubMed

    Tan, Mona Poh-Choo

    2016-02-01

    Breast conservation treatment (BCT) is the preferred modality of treatment for early breast cancer. However, a moderate proportion of women will develop deformity and those with tumours in the lower hemisphere of the breast pose a particular challenge. Here, a technique is described which allows acceptable cosmetic outcome in women with small or medium-sized breasts without the use of therapeutic mammoplasty or volume replacement with flaps. PMID:26855913

  8. Accumulation of radium in ferruginous protein bodies formed in lung tissue: association of resulting radiation hotspots with malignant mesothelioma and other malignancies

    PubMed Central

    Nakamura, Eizo; Makishima, Akio; Hagino, Kyoko; Okabe, Kazunori

    2009-01-01

    While exposure to fibers and particles has been proposed to be associated with several different lung malignancies including mesothelioma, the mechanism for the carcinogenesis is not fully understood. Along with mineralogical observation, we have analyzed forty-four major and trace elements in extracted asbestos bodies (fibers and proteins attached to them) with coexisting fiber-free ferruginous protein bodies from extirpative lungs of individuals with malignant mesothelioma. These observations together with patients’ characteristics suggest that inhaled iron-rich asbestos fibers and dust particles, and excess iron deposited by continuous cigarette smoking would induce ferruginous protein body formation resulting in ferritin aggregates in lung tissue. Chemical analysis of ferruginous protein bodies extracted from lung tissues reveals anomalously high concentrations of radioactive radium, reaching millions of times higher concentration than that of seawater. Continuous and prolonged internal exposure to hotspot ionizing radiation from radium and its daughter nuclides could cause strong and frequent DNA damage in lung tissue, initiate different types of tumour cells, including malignant mesothelioma cells, and may cause cancers. PMID:19644223

  9. Platelet sensitivity to prostacyclin in normal subjects, and in patients with benign and malignant tumours of the breast.

    PubMed Central

    Benedetto, C.; Zonca, M.; Tavella, A. M.; Petitti, E.; Massobrio, M.; Nigam, S.; Slater, T. F.

    1985-01-01

    Platelet sensitivity to prostacyclin (PG12) was determined in normal male and female subjects, and in patients with benign and malignant tumours of the breast. The IC50 overall mean values for PG12 on ADP-induced platelet aggregation were similar for normal men and women, being 0.97 +/- 0.05 ng ml-1 and 0.83 +/- 0.07 ng ml-1 respectively. However, there were significant differences in the IC50 values for women in the 1st (0.81 +/- 0.06 ng ml-1) vs. 2nd (1.37 +/- 0.13 ng ml-1) phase of the menstrual cycle; post-menopausal women gave similar values to normal males and to pre-menopausal women in the 1st phase of the cycle. No significant differences were found between normal subjects and patients with benign or malignant tumours of the breast when account was taken of the status of the patient in relation to the phase of the menstrual cycle and the menopause. The importance of the hormonal status in evaluating changes in platelet sensitivity in patients with breast cancer is strongly emphasised. PMID:3881119

  10. Premalignant and Malignant Skin Lesions in Two Recipients of Vascularized Composite Tissue Allografts (Face, Hands)

    PubMed Central

    Kanitakis, Jean; Petruzzo, Palmina; Gazarian, Aram; Testelin, Sylvie; Devauchelle, Bernard; Badet, Lionel; Dubernard, Jean-Michel; Morelon, Emmanuel

    2015-01-01

    Recipients of solid organ transplants (RSOT) have a highly increased risk for developing cutaneous premalignant and malignant lesions, favored by the lifelong immunosuppression. Vascularized composite tissue allografts (VCA) have been introduced recently, and relevant data are sparse. Two patients with skin cancers (one with basal cell carcinoma and one with squamous cell carcinomas) have been so far reported in this patient group. Since 2000 we have been following 9 recipients of VCA (3 face, 6 bilateral hands) for the development of rejection and complications of the immunosuppressive treatment. Among the 9 patients, one face-grafted recipient was diagnosed with nodular-pigmented basal cell carcinoma of her own facial skin 6 years after graft, and one patient with double hand allografts developed disseminated superficial actinic porokeratosis, a potentially premalignant dermatosis, on her skin of the arm and legs. Similar to RSOT, recipients of VCA are prone to develop cutaneous premalignant and malignant lesions. Prevention should be applied through sun-protective measures, regular skin examination, and early treatment of premalignant lesions. PMID:26550517

  11. Premalignant and Malignant Skin Lesions in Two Recipients of Vascularized Composite Tissue Allografts (Face, Hands).

    PubMed

    Kanitakis, Jean; Petruzzo, Palmina; Gazarian, Aram; Testelin, Sylvie; Devauchelle, Bernard; Badet, Lionel; Dubernard, Jean-Michel; Morelon, Emmanuel

    2015-01-01

    Recipients of solid organ transplants (RSOT) have a highly increased risk for developing cutaneous premalignant and malignant lesions, favored by the lifelong immunosuppression. Vascularized composite tissue allografts (VCA) have been introduced recently, and relevant data are sparse. Two patients with skin cancers (one with basal cell carcinoma and one with squamous cell carcinomas) have been so far reported in this patient group. Since 2000 we have been following 9 recipients of VCA (3 face, 6 bilateral hands) for the development of rejection and complications of the immunosuppressive treatment. Among the 9 patients, one face-grafted recipient was diagnosed with nodular-pigmented basal cell carcinoma of her own facial skin 6 years after graft, and one patient with double hand allografts developed disseminated superficial actinic porokeratosis, a potentially premalignant dermatosis, on her skin of the arm and legs. Similar to RSOT, recipients of VCA are prone to develop cutaneous premalignant and malignant lesions. Prevention should be applied through sun-protective measures, regular skin examination, and early treatment of premalignant lesions. PMID:26550517

  12. Minimally invasive and ex-vivo diagnostics of breast cancer tissues by fiber optic evanescent-wave Fourier transform IR (FEW-FTIR) spectroscopy

    NASA Astrophysics Data System (ADS)

    Afanasyeva, Natalia I.; Kolyakov, Sergei F.; Artioushenko, Vjacheslav G.; Sokolov, Victor V.; Frank, George A.

    1998-04-01

    Fourier transform IR fiberoptic evanescent wave spectroscopy has been suggested as a powerful tool for clinical diagnostics of normal, precancerous, and cancerous breast tissue ex vivo and in vitro in the middle IR region of the spectrum. This method is suitable for noninvasive and direct measurements of the spectra of normal and pathological tissues in vitro, ex vivo and in vivo. For the first time this method has been used nondestructively, rapidly, fast and remotely in the operating rooms of clinics. The aim of our studies has been the express testing of various tumor tissues during surgery to optimize and localize an area of removing tissue. We measured very small samples of normal and malignant breast tissue ex vivo with a fiber bent to a special angle, forming a special tip probe configuration. We also suggest her the minimally invasive FTIR-FEW diagnosis tool using 'needle' changeable tip probe for biopsy applications. The spectral histopathology branching could be developed with help of this technique in vitro. The breast tissue at different stages of tumor or cancer has been distinguished very clearly in spectra of amide, cyclic and noncyclic hydrogen bonded fragments, phosphate groups and sugars.

  13. Mapping transitions between healthy and pathological lesions in human breast tissues by diffraction enhanced imaging computed tomography (DEI-CT) and small angle x-ray scattering (SAXS)

    NASA Astrophysics Data System (ADS)

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

    2014-02-01

    In this work we have combined the DEI-CT and SAXS technique to study the transition between healthy and pathological breast tissues, which include benign and malignant lesions. The ability of DEI-CT to enhance the contrast between soft tissues was used to localize the tumor region in the sample. Then, the tumor region and its surroundings were scanned by SAXS in order to map the changes promoted by the neoplasias at nano-level.It was clearly observed that pathological tissues present distinguishable SAXS scattering profiles from those of normal tissue. These differences are mainly related to changes in arrangement and diameter of collagen fibrils, evaluated by the higher order of reflection peaks of these fibrils. Differences related to the peak intensities and the total scattered intensity were found by comparing the healthy and pathological regions. The 2nd order of collagen reflection arises only in the healthy region neighboring the benign lesion. A broader peak at q=0.16 nm-1 seems to characterize the malignant lesions. Finally, based on this information, the transition between healthy and pathological human breast tissues was mapped which allowed to get insights into the changes promoted by tumors during growth and progression.

  14. Control of sulfatase activity by nomegestrol acetate in normal and cancerous human breast tissues.

    PubMed

    Chetrite, Gérard Samuel; Thomas, Jean-Louis; Shields-Botella, Jaqueline; Cortes-Prieto, Joaquin; Philippe, Jean-Claude; Pasqualini, Jorge Raul

    2005-01-01

    Nomegestrol acetate (NOMAC), a 17alpha-hydroxy-nor-progesterone derivative (17alpha-acetoxy-6-methyl-19-nor-4,6-pregnadiene-3,20-dione, the active substance in Lutenyl), is a potent and useful clinical synthetic progestin for the treatment of menopausal complaints and is under current development for oral contraception. Previous studies in this laboratory demonstrated that NOMAC can block sulfatase and 17beta-hydroxysteroid dehydrogenase, the enzymes involved in the biosynthesis and transformation of estradiol (E2) in hormone-dependent MCF-7 and T-47D breast cancer cells. In the present study, the effect of NOMAC on sulfatase activity using total breast cancer tissue, compared to the effect in normal breast tissue, was explored. Slices of tumoral or normal breast tissues (45-65 mg) were incubated in buffer (20 mM Tris-HCl, pH 7.2) with physiological concentrations of [3H]-estrone sulfate (5x10(-9) M), alone or in the presence of nomegestrol acetate (5x10(-5) - 5x10(-7) - 5x10(-9) M), for 4 h at 37 degrees C. Estrone sulfate (E1S), estrone (E1) and E2 were characterized by thin layer chromatography and quantified using the corresponding standard. It was observed that [3H]- E1S was only converted to [3H]- E1 and not to [3H]- E2, in normal or cancerous breast tissues, which suggests a low or no 17beta-HSD activity under these experimental conditions. The sulfatase activity was more intense with breast cancer tissue than normal tissue, since the concentrations of E1 were 42.5 +/- 3.4 and 27.2 +/- 2.5 pg/mg tissue, respectively. NOMAC, at the concentration of 5x10(-5) M, inhibited this conversion by 49.2% and 40.8% in cancerous and normal breast tissues, respectively. The sulfatase inhibition at low concentration (5x10(-7) M) was 32.5% and 22.8%, respectively. It is concluded that sulfatase activity is almost twice as potent in cancerous breast tissues than in normal tissues. Nomegestrol acetate is a strong anti-sulfatase agent, in particular with cancerous breast

  15. Tissue Expander Placement to Prevent the Adverse Intestinal Effects of Radiotherapy in Malignant Pelvic Tumors.

    PubMed

    Uehara, Shuichiro; Oue, Takaharu; Adachi, Kana; Yoshioka, Yasuo; Nakahata, Kengo; Ueno, Takehisa; Okuyama, Hiroomi

    2016-03-01

    We herein report the findings of 3 patients with primary Ewing sarcoma in a pelvic lesion who underwent the placement of a tissue expander (TE) before radiation therapy to prevent the adverse effects of radiotherapy. The simulation study showed that the TE drastically reduced volume of the intestine that was irradiated at all dose levels. All patients could receive the scheduled dose of radiotherapy without any acute and late complications such as diarrhea, melena, the dislodging of the TE, infection, or the formation of fistulae. In the 4-year (minimum) observation period, we did not observe intestinal complications in any of our patients. TE placement is considered to be a safe and effective method for preventing the adverse effects of radiotherapy in pediatric malignant pelvic tumors. PMID:26479989

  16. Laser-induced fluorescence in malignant and normal tissue in mice injected with two different carotenoporphyrins.

    PubMed Central

    Nilsson, H.; Johansson, J.; Svanberg, K.; Svanberg, S.; Jori, G.; Reddi, E.; Segalla, A.; Gust, D.; Moore, A. L.; Moore, T. A.

    1994-01-01

    Laser-induced fluorescence (LIF) was used to characterise the localisation of an intravenously administered trimethylated carotenoporphyrin [CP(Me)3] and a trimethoxylated carotenoporphyrin [CP(OMe)3] in an intramuscularly transplanted malignant tumour (MS-2 fibrosarcoma) and healthy muscle in female Balb/c mice, 3, 24, 48 and 96 h post injection. The fluorescence was induced with a dye laser pumped by a nitrogen laser, emitting light at 425 nm. The fluorescence spectra were recorded in the region 455-760 nm using a polychromator equipped with an image-intensified CCD camera. The tumour/peritumoral muscle ratio was about 5:1 for CP(Me)3 and about 6:1 for CP(OMe)3 in terms of the background-free fluorescence intensity, which peaked at about 655 nm. By including the endogenous tissue fluorescence, the contrast was further enhanced by a factor of approximately 2. PMID:7947092

  17. 21st century paradigm of tissue banking: the Clinical Breast Care Project.

    PubMed

    Shriver, Craig D

    2010-07-01

    The Clinical Breast Care Project (CBCP) is a congressionally mandated program that began in the year 2000. The military-civilian collaboration was founded on five pillars: (1) center of excellence in clinical care, (2) risk reduction for women at risk for developing breast cancer, (3) tissue banking to develop and maintain the world's finest repository of human biospecimens of breast diseases, (4) targeted research into the molecular signatures of breast diseases and cancer, and (5) biomedical informatics core to support the data warehouse needs of the project. Now in its eighth year of operation, these efforts have resulted in more than 300 peer-reviewed scientific publications and dozens of collaborations with world leaders in cancer research. In this short time, CBCP has created what is believed to be the world's largest breast tissue biorepository. PMID:23634480

  18. Microwave Radar Imaging of Heterogeneous Breast Tissue Integrating A Priori Information

    PubMed Central

    Kelly, Thomas N.; Sarafianou, Mantalena; Craddock, Ian J.

    2014-01-01

    Conventional radar-based image reconstruction techniques fail when they are applied to heterogeneous breast tissue, since the underlying in-breast relative permittivity is unknown or assumed to be constant. This results in a systematic error during the process of image formation. A recent trend in microwave biomedical imaging is to extract the relative permittivity from the object under test to improve the image reconstruction quality and thereby to enhance the diagnostic assessment. In this paper, we present a novel radar-based methodology for microwave breast cancer detection in heterogeneous breast tissue integrating a 3D map of relative permittivity as a priori information. This leads to a novel image reconstruction formulation where the delay-and-sum focusing takes place in time rather than range domain. Results are shown for a heterogeneous dense (class-4) and a scattered fibroglandular (class-2) numerical breast phantom using Bristol's 31-element array configuration. PMID:25435861

  19. Expression of glucocorticoid and progesterone nuclear receptor genes in archival breast cancer tissue

    PubMed Central

    Smith, Robert A; Lea, Rod A; Curran, Joanne E; Weinstein, Stephen R; Griffiths, Lyn R

    2003-01-01

    Background Previous studies in our laboratory have shown associations of specific nuclear receptor gene variants with sporadic breast cancer. In order to investigate these findings further, we conducted the present study to determine whether expression levels of the progesterone and glucocorticoid nuclear receptor genes vary in different breast cancer grades. Methods RNA was extracted from paraffin-embedded archival breast tumour tissue and converted into cDNA. Sample cDNA underwent PCR using labelled primers to enable quantitation of mRNA expression. Expression data were normalized against the 18S ribosomal gene multiplex and analyzed using analysis of variance. Results Analysis of variance indicated a variable level of expression of both genes with regard to breast cancer grade (P = 0.00033 for glucocorticoid receptor and P = 0.023 for progesterone receptor). Conclusion Statistical analysis indicated that expression of the progesterone nuclear receptor is elevated in late grade breast cancer tissue. PMID:12559052

  20. Average dielectric property analysis of complex breast tissue with microwave transmission measurements.

    PubMed

    Garrett, John D; Fear, Elise C

    2015-01-01

    Prior information about the average dielectric properties of breast tissue can be implemented in microwave breast imaging techniques to improve the results. Rapidly providing this information relies on acquiring a limited number of measurements and processing these measurement with efficient algorithms. Previously, systems were developed to measure the transmission of microwave signals through breast tissue, and simplifications were applied to estimate the average properties. These methods provided reasonable estimates, but they were sensitive to multipath. In this paper, a new technique to analyze the average properties of breast tissues while addressing multipath is presented. Three steps are used to process transmission measurements. First, the effects of multipath were removed. In cases where multipath is present, multiple peaks were observed in the time domain. A Tukey window was used to time-gate a single peak and, therefore, select a single path through the breast. Second, the antenna response was deconvolved from the transmission coefficient to isolate the response from the tissue in the breast interior. The antenna response was determined through simulations. Finally, the complex permittivity was estimated using an iterative approach. This technique was validated using simulated and physical homogeneous breast models and tested with results taken from a recent patient study. PMID:25585106

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

    PubMed

    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. PMID:27135363

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

    PubMed Central

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

    2012-01-01

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

  3. Atypical Proliferating Trichilemmal Cyst with Malignant Breast Skin Transformation: A Case Report and Review of the Literature

    PubMed Central

    Capurso-García, Marino Antonio; Bautista-Piña, Verónica; Pomerantz, Alan; Galnares-Olalde, Javier Andrés; Blachman-Braun, Ruben; Rodríguez-Rodríguez, Sergio; Goldberg-Murow, Monica

    2016-01-01

    Proliferating trichilemmal tumors (PTTs) are benign adnexal skin neoplasms that arise from the outer root sheath of the hair follicle. These tumors are most commonly observed on the scalp and occur, most of the time, in elderly women. Malignant transformation of these neoplasms is a rare event; less than 50 cases have been reported in the English medical literature. We present the case of a 39-year-old Hispanic woman with a tumor located on the skin of one of her breasts that in her third surgical procedure the histologic examination revealed the presence of a malignant proliferating trichilemmal tumor (MPTT). Furthermore, a review of the medical literature and a discussion of the clinical and pathologic features of this rare entity are provided. PMID:27403361

  4. Atypical Proliferating Trichilemmal Cyst with Malignant Breast Skin Transformation: A Case Report and Review of the Literature.

    PubMed

    Capurso-García, Marino Antonio; Bautista-Piña, Verónica; Pomerantz, Alan; Galnares-Olalde, Javier Andrés; Blachman-Braun, Ruben; Rodríguez-Rodríguez, Sergio; Goldberg-Murow, Monica

    2016-01-01

    Proliferating trichilemmal tumors (PTTs) are benign adnexal skin neoplasms that arise from the outer root sheath of the hair follicle. These tumors are most commonly observed on the scalp and occur, most of the time, in elderly women. Malignant transformation of these neoplasms is a rare event; less than 50 cases have been reported in the English medical literature. We present the case of a 39-year-old Hispanic woman with a tumor located on the skin of one of her breasts that in her third surgical procedure the histologic examination revealed the presence of a malignant proliferating trichilemmal tumor (MPTT). Furthermore, a review of the medical literature and a discussion of the clinical and pathologic features of this rare entity are provided. PMID:27403361

  5. Cadherin expression in gastrointestinal tract endometriosis: possible role in deep tissue invasion and development of malignancy.

    PubMed

    Van Patten, Katy; Parkash, Vinita; Jain, Dhanpat

    2010-01-01

    all study cases. These results strongly suggest that alterations of N-cadherin expression in gastrointestinal endometriosis may have an important role in the mechanism that underlies deep tissue invasion, and possibly also in the development of malignancy. PMID:19898423

  6. Breast-related effects of selective estrogen receptor modulators and tissue-selective estrogen complexes

    PubMed Central

    2014-01-01

    A number of available treatments provide relief of menopausal symptoms and prevention of postmenopausal osteoporosis. However, as breast safety is a major concern, new options are needed, particularly agents with an improved mammary safety profile. Results from several large randomized and observational studies have shown an association between hormone therapy, particularly combined estrogen-progestin therapy, and a small increased risk of breast cancer and breast pain or tenderness. In addition, progestin-containing hormone therapy has been shown to increase mammographic breast density, which is an important risk factor for breast cancer. Selective estrogen receptor modulators (SERMs) provide bone protection, are generally well tolerated, and have demonstrated reductions in breast cancer risk, but do not relieve menopausal symptoms (that is, vasomotor symptoms). Tissue-selective estrogen complexes (TSECs) pair a SERM with one or more estrogens and aim to blend the positive effects of the components to provide relief of menopausal symptoms and prevention of postmenopausal osteoporosis without stimulating the breast or endometrium. One TSEC combination pairing conjugated estrogens (CEs) with the SERM bazedoxifene (BZA) has completed clinical development and is now available as an alternative option for menopausal therapy. Preclinical evidence suggests that CE/BZA induces inhibitory effects on breast tissue, and phase 3 clinical studies suggest breast neutrality, with no increases seen in breast tenderness, breast density, or cancer. In non-hysterectomized postmenopausal women, CE/BZA was associated with increased bone mineral density and relief of menopausal symptoms, along with endometrial safety. Taken together, these results support the potential of CE/BZA for the relief of menopausal symptoms and prevention of postmenopausal osteoporosis combined with breast and endometrial safety. PMID:25928299

  7. High-intensity focused ultrasound in breast pathology: non-invasive treatment of benign and malignant lesions.

    PubMed

    Cavallo Marincola, Beatrice; Pediconi, Federica; Anzidei, Michele; Miglio, Elena; Di Mare, Luisa; Telesca, Marianna; Mancini, Massimiliano; D'Amati, Giulia; Monti, Massimo; Catalano, Carlo; Napoli, Alessandro

    2015-03-01

    Breast neoplasms are one of the leading causes of morbidity and mortality in women. Even if surgery is the treatment of choice, other forms of less invasive radical treatment are desirable. High-intensity focused ultrasound is already established as a valid non-invasive technique that ensures tumor ablation in various organs. The use of ultrasound or magnetic resonance guidance allows having some advantages such as the capability to treat tumors in moving organs or the possibility to have a real-time monitoring of the temperature increase. The aim of this paper is to report the use of high-intensity focused ultrasound technique with ultrasound and magnetic resonance guidance for the ablation of breast tumors, including both benign and malignant lesions. PMID:25418428

  8. Accurate Characterization of Benign and Cancerous Breast Tissues: Aspecific Patient Studies using Piezoresistive Microcantilevers

    PubMed Central

    PANDYA, HARDIK J.; ROY, RAJARSHI; CHEN, WENJIN; CHEKMAREVA, MARINA A.; FORAN, DAVID J.; DESAI, JAYDEV P.

    2014-01-01

    Breast cancer is the largest detected cancer amongst women in the US. In this work, our team reports on the development of piezoresistive microcantilevers (PMCs) to investigate their potential use in the accurate detection and characterization of benign and diseased breast tissues by performing indentations on the micro-scale tissue specimens. The PMCs used in these experiments have been fabricated using laboratory-made silicon-on-insulator (SOI) substrate, which significantly reduces the fabrication costs. The PMCs are 260 μm long, 35 μm wide and 2 μm thick with resistivity of order 1.316 X 10−3 Ω-cm obtained by using boron diffusion technique. For indenting the tissue, we utilized 8 μm thick cylindrical SU-8 tip. The PMC was calibrated against a known AFM probe. Breast tissue cores from seven different specimens were indented using PMC to identify benign and cancerous tissue cores. Furthermore, field emission scanning electron microscopy (FE-SEM) of benign and cancerous specimens showed marked differences in the tissue morphology, which further validates our observed experimental data with the PMCs. While these patient aspecific feasibility studies clearly demonstrate the ability to discriminate between benign and cancerous breast tissues, further investigation is necessary to perform automated mechano-phenotyping (classification) of breast cancer: from onset to disease progression. PMID:25128621

  9. Validation of a power-law noise model for simulating small-scale breast tissue

    PubMed Central

    Reiser, I.; Edwards, A.; Nishikawa, R. M.

    2013-01-01

    We have validated a small-scale breast tissue model based on power-law noise. A set of 110 patient images served as truth. The statistical model parameters were determined by matching the radially-averaged power-spectrum of the projected simulated tissue with that of the central tomosynthesis patient breast projections. Observer performance in a signal-known exactly detection task in simulated and actual breast backgrounds was compared. Observers included human readers, a pre-whitening observer model and a channelized Hotelling observer model. For all observers, good agreement between performance in the simulated and actual backgrounds was found, both in the tomosynthesis central projections and the reconstructed images. This tissue model can be used for breast x-ray imaging system optimization. The complete statistical description of the model is provided. PMID:23938858

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

    PubMed

    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. PMID:22804110

  11. Validation of a power-law noise model for simulating small-scale breast tissue

    NASA Astrophysics Data System (ADS)

    Reiser, I.; Edwards, A.; Nishikawa, R. M.

    2013-09-01

    We have validated a small-scale breast tissue model based on power-law noise. A set of 110 patient images served as truth. The statistical model parameters were determined by matching the radially averaged power-spectrum of the projected simulated tissue with that of the central tomosynthesis patient breast projections. Observer performance in a signal-known exactly detection task in simulated and actual breast backgrounds was compared. Observers included human readers, a pre-whitening observer model and a channelized Hotelling observer model. For all observers, good agreement between performance in the simulated and actual backgrounds was found, both in the tomosynthesis central projections and the reconstructed images. This tissue model can be used for breast x-ray imaging system optimization. The complete statistical description of the model is provided.

  12. Reliability and validity of an instrument to measure tissue hardness in breasts.

    PubMed

    Roberts, K L

    The author investigated the effectiveness of the Roberts Durometer, an instrument developed to measure human tissue hardness for a study on breast engorgement. The instrument is a small portable pressure gauge comprising a probe attached to a spring and contained in a tubular housing, connected to a dial gauge. The instrument was first trialed using foam rubber of differing hardness and football bladders of differing hardness. It was then used to measure the hardness of a non-pregnant, non-lactating human breast, followed by trials on postpartum women comparing breast tissue hardness on the day of birth with that of subsequent days. The instrument detected significant differences in hardness of foams, football bladders and human breast tissue. It was therefore considered suitable for measuring, in both research and clinical applications, hardness of breast tissue, which is a major physical feature of breast engorgement. Other clinical applications could include the hardness of abdominal and other skin tissues in conditions such as ascites, peritonitis and cellulitis. PMID:10196872

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

    NASA Astrophysics Data System (ADS)

    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. Investigating Breast Cancer Cell Behavior Using Tissue Engineering Scaffolds

    PubMed Central

    Guiro, Khadidiatou; Patel, Shyam A.; Greco, Steven J.; Rameshwar, Pranela; Arinzeh, Treena L.

    2015-01-01

    Despite early detection through the use of mammograms and aggressive intervention, breast cancer (BC) remains a clinical dilemma. BC can resurge after >10 years of remission. Studies indicate that BC cells (BCCs) with self-renewal and chemoresistance could be involved in dormancy. The majority of studies use in vitro, two-dimensional (2-D) monolayer cultures, which do not recapitulate the in vivo microenvironment. Thus, to determine the effect of three-dimensional (3-D) microenvironment on BCCs, this study fabricated tissue engineering scaffolds made of poly (ε-caprolactone) (PCL) having aligned or random fibers. Random and aligned fibers mimic, respectively, the random and highly organized collagen fibers found in the tumor extracellular matrix. Chemoresistant BCCs were obtained by treating with carboplatin. Western blot analysis of carboplatin resistant (treated) MDA-MB-231 (highly invasive, basal-like) and T47D (low-invasive, luminal) BCCs showed an increase in Bcl-2, Oct-4 and Sox-2, suggesting protection from apoptosis and increase in stem-like markers. Further studies with MDA-MB-231 BCCs seeded on the scaffolds showed little to no change in cell number over time for non-treated BCCs whereas on tissue culture polystyrene (TCP), non-treated BCCs displayed a significant increase in cell number at days 4 and 7 as compared to day 1 (p<0.05). Treated BCCs did not proliferate on TCP and the fibrous scaffolds. Little to no cyclin D1 was expressed for non-treated BCCs on TCP. On fibrous scaffolds, non-treated BCCs stained for cyclin D1 during the 7-day culture period. Treated BCCs expressed cyclin D1 on TCP and fibrous scaffolds during the 7-day culture period. Proliferation, viability and cell cycle analysis indicated that this 3-D culture prompted the aggressive BCCs to adopt a dormant phenotype, while the treated BCCs retained their phenotype. The findings indicate that random and aligned fibrous PCL scaffolds may provide a useful system to study how the 3-D

  15. β class II tubulin predominates in normal and tumor breast tissues

    PubMed Central

    Dozier, James H; Hiser, Laree; Davis, Jennifer A; Thomas, Nancy Stubbs; Tucci, Michelle A; Benghuzzi, Hamed A; Frankfurter, Anthony; Correia, John J; Lobert, Sharon

    2003-01-01

    Background Antimitotic chemotherapeutic agents target tubulin, the major protein in mitotic spindles. Tubulin isotype composition is thought to be both diagnostic of tumor progression and a determinant of the cellular response to chemotherapy. This implies that there is a difference in isotype composition between normal and tumor tissues. Methods To determine whether such a difference occurs in breast tissues, total tubulin was fractionated from lysates of paired normal and tumor breast tissues, and the amounts of β-tubulin classes I + IV, II, and III were measured by competitive enzyme-linked immunosorbent assay (ELISA). Only primary tumor tissues, before chemotherapy, were examined. Her2/neu protein amplification occurs in about 30% of breast tumors and is considered a marker for poor prognosis. To gain insight into whether tubulin isotype levels might be correlated with prognosis, ELISAs were used to quantify Her2/neu protein levels in these tissues. Results β-Tubulin isotype distributions in normal and tumor breast tissues were similar. The most abundant β-tubulin isotypes in these tissues were β-tubulin classes II and I + IV. Her2/neu levels in tumor tissues were 5–30-fold those in normal tissues, although there was no correlation between the Her2/neu biomarker and tubulin isotype levels. Conclusion These results suggest that tubulin isotype levels, alone or in combination with Her2/neu protein levels, might not be diagnostic of tumorigenesis in breast cancer. However, the presence of a broad distribution of these tubulin isotypes (for example, 40–75% β-tubulin class II) in breast tissue, in conjunction with other factors, might still be relevant to disease progression and cellular response to antimitotic drugs. PMID:12927047

  16. Risk of Second Primary Malignancy in Breast Cancer Survivors: A Nested Population-Based Case-Control Study

    PubMed Central

    Marcheselli, Raffaella; Cortesi, Laura; Bari, Alessia; Cirilli, Claudia; Pozzi, Samantha; Ferri, Paola; Napolitano, Martina; Federico, Massimo; Sacchi, Stefano

    2015-01-01

    Purpose Evolving therapies have improved the prognoses of patients with breast cancer; and currently, the number of long-term survivors is continuously increasing. However, these patients are at increased risk of developing a second cancer. Thus, late side effects are becoming an important issue. In this study, we aimed to investigate whether patient and tumor characteristics, and treatment type correlate with secondary tumor risk. Methods This case-control study included 305 patients with a diagnosed second malignancy after almost 6 months after the diagnosis of primary breast cancer and 1,525 controls (ratio 1:5 of cases to controls) from a population-based cohort of 6,325 women. The control patients were randomly selected from the cohort and matched to the cases according to age at diagnosis, calendar period of diagnosis, disease stage, and time of follow-up. Results BRCA1 or BRCA2 mutation, human epidermal growth factor receptor 2 (HER2)+ status, chemotherapy, and radiotherapy were related to increased risk of developing a second cancer, whereas hormonotherapy showed a protective effect. Chemotherapy, radiotherapy, and estrogenic receptor level <10% increased the risk of controlateral breast cancer. HER2+ status increased the risk of digestive system and thyroid tumors, while BRCA1 or BRCA2 mutation increased the risk of cancer in the genital system. Conclusion Breast cancer survivors are exposed to an excess of risk of developing a second primary cancer. The development of excess of malignancies may be related either to patient and tumor characteristics, such as BRCA1 or BRCA2 mutation and HER2+ status, or to treatments factors. PMID:26770245

  17. Transcatheter Arterial Embolization for Malignant Osseous and Soft Tissue Sarcomas. II. Clinical Results

    SciTech Connect

    Nagata, Yasushi; Mitsumori, Michihide; Okajima, Kaoru; Mizowaki, Takashi; Fujiwara, Kazuhisa; Sasai, Keisuke; Nishimura, Yasumasa; Hiraoka, Masahiro; Abe, Mitsuyuki; Shimizu, Katsuji; Kotoura, Yoshihiko

    1998-05-15

    Purpose: To evaluate the clinical effects of transcatheter arterial embolization (TAE) on malignant bone and soft tissue tumors. Methods: TAE was performed in 10 patients with primary bone and soft tissue sarcomas and in 31 patients with metastatic bone tumors. The embolized arteries were the internal iliac artery in 30 cases, the intercostal artery in six cases, the lumbar artery in five cases, the suprascapular artery in three cases, and the iliolumbar artery, the internal pudendal artery, and the lateral sacral artery in one case each. The embolized material was gelatin sponge particles. The chemotherapeutic drugs were usually 20-40 mg of doxorubicin for primary and metastatic tumors and 50-100 mg of cisplatin only for primary tumors. In addition, 50-60 Gy of 10-MV radiotherapy with or without radiofrequency (RF)-capacitive hyperthermia in four sessions was administered before TAE for primary tumors only. Results: Even though the pain score increased immediately after TAE, 30 of 38 (79%) patients with pain (8 of 9 with primary tumors, and 22 of 29 with metastases) achieved pain control after TAE. A necrotic low-density area shown by computed tomography (CT) after TAE was found in 31 of 41 (76%) tumors [8 of 10 (80%) with primary tumors, and 23 of 31 (74%) with metastatic tumors]. The tumor size decreased in 14 of 25 (56%) primary and metastatic tumors after 3 months. Osteosclerotic changes appeared in two cases of metastatic tumors after 6 months. In five tumors resected after TAE, large areas of necrosis within the tumor were confirmed histologically. Transient local pain and numbness appeared after TAE, but were relieved by drug treatment within 1 week. No severe complications except a case of gluteal muscle necrosis were encountered after TAE. The 1-year survival rate of the patients with primary tumors was 38.1%, and the median survival was 18 months. The longest survival was 84 months. The 1-year survival rate of the patients with metastatic bone tumors was

  18. Transacatheter arterial embolization for malignant osseous and soft tissue sarcomas. II. Clinical results

    SciTech Connect

    Nagata, Yasushi; Mitsumori, Michihide; Okajima, Kaoru; Mizowaki, Takashi; Fujiwara, Kazuhisa; Sasai, Keisuke; Nishimura, Yasumasa; Hiraoka, Masahiro; Abe, Mitsuyuki; Shimizu, Katsuji; Kotoura, Yoshihiko

    1998-05-15

    Purpose: To evaluate the clinical effects of transcatheter arterial embolization (TAE) on malignant bone and soft tissue tumors.Methods: TAE was performed in 10 patients with primary bone and soft tissue sarcomas and in 31 patients with metastatic bone tumors. The embolized arteries were the internal iliac artery in 30 cases, the intercostal artery in six cases, the lumbar artery in five cases, the suprascapular artery in three cases, and the iliolumbar artery, the internal pudendal artery, and the lateral sacral artery in one case each. The embolized material was gelatin sponge particles. The chemotherapeutic drugs were usually 20-40 mg of doxorubicin for primary and metastatic tumors and 50-100 mg of cisplatin only for primary tumors. In addition, 50-60 Gy of 10-MV radiotherapy with or without radiofrequency (RF)-capacitive hyperthermia in four sessions was administered before TAE for primary tumors only.Results: Even though the pain score increased immediately after TAE, 30 of 38 (79%) patients with pain (8 of 9 with primary tumors, and 22 of 29 with metastases) achieved pain control after TAE. A necrotic low-density area shown by computed tomography (CT) after TAE was found in 31 of 41 (76%) tumors [8 of 10 (80%) with primary tumors, and 23 of 31 (74%) with metastatic tumors]. The tumor size decreased in 14 of 25 (56%) primary and metastatic tumors after 3 months. Osteosclerotic changes appeared in two cases of metastatic tumors after 6 months. In five tumors resected after TAE, large areas of necrosis within the tumor were confirmed histologically. Transient local pain and numbness appeared after TAE, but were relieved by drug treatment within 1 week. No severe complications except a case of gluteal muscle necrosis were encountered after TAE. The 1-year survival rate of the patients with primary tumors was 38.1%, and the median survival was 18 months. The longest survival was 84 months. The 1-year survival rate of the patients with metastatic bone tumors was

  19. Limb Preservation With Isolated Limb Infusion for Locally Advanced Nonmelanoma Cutaneous and Soft-Tissue Malignant Neoplasms

    PubMed Central

    Turaga, Kiran K.; Beasley, Georgia M.; Kane, John M.; Delman, Keith A.; Grobmyer, Stephen R.; Gonzalez, Ricardo J.; Letson, G. Douglas; Cheong, David; Tyler, Douglas S.; Zager, Jonathan S.

    2015-01-01

    Objective To demonstrate the efficacy of isolated limb infusion (ILI) in limb preservation for patients with locally advanced soft-tissue sarcomas and nonmelanoma cutaneous malignant neoplasms. Background Locally advanced nonmelanoma cutaneous and soft-tissue malignant neoplasms, including soft-tissue sarcomas of the extremities, can pose significant treatment challenges. We report our experience, including responses and limb preservation rates, using ILI in cutaneous and soft-tissue malignant neoplasms. Methods We identified 22 patients with cutaneous and soft-tissue malignant neoplasms who underwent 26 ILIs with melphalan and actinomycin from January 1, 2004, through December 31, 2009, from 5 institutions. Outcome measures included limb preservation and in-field response rates. Toxicity was measured using the Wieberdink scale and serum creatinine phosphokinase levels. Results The median age was 70 years (range, 19-92 years), and 12 patients (55%) were women. Fourteen patients (64%) had sarcomas, 7 (32%) had Merkel cell carcinoma, and 1 (5%) had squamous cell carcinoma. The median length of stay was 5.5 days (interquartile range, 4-8 days). Twenty-five of the 26 ILIs (96%) resulted in Wieberdink grade III or less toxicity, and 1 patient (4%) developed grade IV toxicity. The median serum creatinine phosphokinase level was 127 U/L for upper extremity ILIs and 93 U/L for lower extremity ILIs. Nineteen of 22 patients (86%) underwent successful limb preservation. The 3-month in-field response rate was 79% (21% complete and 58% partial), and the median follow-up was 8.6 months (range, 1-63 months). Five patients underwent resection of disease after an ILI, of whom 80% are disease free at a median of 8.6 months. Conclusions Isolated limb infusion provides an attractive alternative therapy for regional disease control and limb preservation in patients with limb-threatening cutaneous and soft-tissue malignant neoplasms. Short-term response rates appear encouraging, yet

  20. Breast Cancer

    MedlinePlus

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

  1. Comparison of trace elements in the scalp hair of malignant and benign breast lesions versus healthy women.

    PubMed

    Pasha, Qaisara; Malik, Salman A; Shaheen, Nazia; Shah, Munir H

    2010-05-01

    Trace elements including Al, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, Pb, Sb, Sr, and Zn were analyzed in the scalp hair samples of women with malignant breast lesions, women with benign breast lesions, and healthy donors using atomic absorption spectrophotometric method. In the scalp hair of malignant-tumor patients, the highest average concentration was shown by Ca (1,187 microg/g), followed by Na (655 microg/g), Mg (478 microg/g), Zn (391 microg/g), Sr (152 microg/g), Fe (114 microg/g), and K (89.8), while in the case of benign-tumor patients, the average estimated element levels were 1,522, 1,093, 572, 457, 217, 80.4, and 74.7 microg/g, respectively. Most of the elements exhibited non-normal distribution evidenced by large spread, standard error, and skewness values. Mean concentrations of Ca (634 microg/g), Zn (206 microg/g), Mg (162 microg/g), Fe (129 microg/g), and Na (82.1 microg/g) were noteworthy in the scalp hair of healthy women. Average levels of Na, Sr, K, Cd, Co, Pb, Mg, Ca, Zn, Ni, Sb, and Mn were revealed to be significantly higher in the hair of malignant and benign patients compared to the healthy women; however, Fe, Cu, Al, and Cr were not significantly different in the scalp hair of the three groups. The quartile distributions of Ca, Cd, Co, Cr, K, Mg, Mn, Na, Ni, Pb, Sb, and Sr revealed maximum spread in the scalp hair of malignant and benign groups; nevertheless, Al, Cu, Fe, and Zn exhibited almost comparable quartile levels in the three groups. Strong correlation coefficients were found between Fe and Cd, Al and Na, Mn and Sr, Co and Cr, Cd and Cr, Pb and K, Pb and Mn, Cu and Na, and Al and Fe in the scalp hair of malignant-tumor patients, while Fe and K, Cd and Co, Na and Co, and Cr and Pb showed strong correlations in the scalp hair of benign-tumor patients, both of which were significantly different compared with the healthy subjects. Multivariate cluster analysis also revealed divergent clustering of the elements in the scalp hair of

  2. Automatic tissue classification for high-resolution breast CT images based on bilateral filtering

    NASA Astrophysics Data System (ADS)

    Yang, Xiaofeng; Sechopoulos, Ioannis; Fei, Baowei

    2011-03-01

    Breast tissue classification can provide quantitative measurements of breast composition, density and tissue distribution for diagnosis and identification of high-risk patients. In this study, we present an automatic classification method to classify high-resolution dedicated breast CT images. The breast is classified into skin, fat and glandular tissue. First, we use a multiscale bilateral filter to reduce noise and at the same time keep edges on the images. As skin and glandular tissue have similar CT values in breast CT images, we use morphologic operations to get the mask of the skin based on information of its position. Second, we use a modified fuzzy C-mean classification method twice, one for the skin and the other for the fatty and glandular tissue. We compared our classified results with manually segmentation results and used Dice overlap ratios to evaluate our classification method. We also tested our method using added noise in the images. The overlap ratios for glandular tissue were above 94.7% for data from five patients. Evaluation results showed that our method is robust and accurate.

  3. A Model for Diagnosing Breast Cancerous Tissue from Thermal Images Using Active Contour and Lyapunov Exponent

    PubMed Central

    GHAYOUMI ZADEH, Hossein; HADDADNIA, Javad; MONTAZERI, Alimohammad

    2016-01-01

    Background: The segmentation of cancerous areas in breast images is important for the early detection of disease. Thermal imaging has advantages, such as being non-invasive, non-radiation, passive, quick, painless, inexpensive, and non-contact. Imaging technique is the focus of this research. Methods: The proposed model in this paper is a combination of surf and corners that are very resistant. Obtained features are resistant to changes in rotation and revolution then with the help of active contours, this feature has been used for segmenting cancerous areas. Results: Comparing the obtained results from the proposed method and mammogram show that proposed method is Accurate and appropriate. Benign and malignance of segmented areas are detected by Lyapunov exponent. Values obtained include TP=91.31%, FN=8.69%, FP=7.26%. Conclusion: The proposed method can classify those abnormally segmented areas of the breast, to the Benign and malignant cancer. PMID:27398339

  4. Discrimination of Breast Cancer from Normal Tissue with Raman Spectroscopy and Chemometrics

    NASA Astrophysics Data System (ADS)

    Li, Q.-B.; Wang, W.; Liu, Ch.-H.; Zhang, G.-J.

    2015-07-01

    Conventional Raman spectra of normal and cancerous breast tissues were acquired at an excitation wavelength of 785 nm and subjected to a discrimination analysis. First the spectra were pretreated with wavelet transform and polynomial fitting; next, cancerous tissue was identified by applying an adaptive local hyperplane K-nearest neighbor (ALHK) method to the pretreated spectra. The best discrimination accuracy of the ALHK method was 93.2%. In summary, normal and cancerous breast tissue were accurately distinguished by a miniature laser Raman spectrometer and the chemometrics method (ALHK), which might prove to be a portable and accessible diagnostic system.

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

    SciTech Connect

    Vedantham, Srinivasan; Karellas, Andrew

    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

  6. Discovery and verification of protein differences between Er positive/Her2/neu negative breast tumor tissue and matched adjacent normal breast tissue.

    PubMed

    Weitzel, Lindsay-Rae B; Byers, Tim; Allen, Jenna; Finlayson, Christina; Helmke, Steve M; Hokanson, John E; Hunsucker, Stephen W; Murphy, James R; Newell, Keri; Queensland, Kelly M; Singh, Meenakshi; Wischmeyer, Paul E; Duncan, Mark W; Elias, Anthony

    2010-11-01

    This study was designed to quantify and identify differences in protein levels between tumor and adjacent normal breast tissue from the same breast in 18 women with stage I/II ER positive/Her2/neu negative invasive breast cancer. Eighteen separate difference gel electrophoresis (DIGE) gels were run (1 gel per patient). Relative quantification was based on DIGE analysis. After excision and tryptic digestion, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and peptide mass mapping were used to identify protein spots. Two hundred and forty-three spots were differentially abundant between normal and cancer tissues. Fifty spots were identified: 41 were over abundant and nine were less abundant in cancers than in normal breast tissue. Western blotting provided independent confirmation for three of the most biologically and statistically interesting proteins. All 18 gels were replicated by another technician and 32% of the differentially abundant proteins were verified by the duplicate analysis. Follow-up studies are now examining these proteins as biomarkers in blood. PMID:20087651

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

    PubMed

    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 < 0.0001) higher than women in the lowest tertile. Associations for each individual LCω-3PUFA 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. PMID:26137879

  8. Cyclin E Associates with the Lipogenic Enzyme ATP-Citrate Lyase to Enable Malignant Growth of Breast Cancer Cells.

    PubMed

    Lucenay, Kimberly S; Doostan, Iman; Karakas, Cansu; Bui, Tuyen; Ding, Zhiyong; Mills, Gordon B; Hunt, Kelly K; Keyomarsi, Khandan

    2016-04-15

    Cyclin E is altered in nearly a third of invasive breast cancers where it is a powerful independent predictor of survival in women with stage I-III disease. Full-length cyclin E is posttranslationally cleaved into low molecular weight (LMW-E) isoforms, which are tumor-specific and accumulate in the cytoplasm because they lack a nuclear localization sequence. We hypothesized that aberrant localization of cytosolic LMW-E isoforms alters target binding and activation ultimately contributing to LMW-E-induced tumorigenicity. To address this hypothesis, we used a retrovirus-based protein complementation assay to find LMW-E binding proteins in breast cancer, identifying ATP-citrate lyase (ACLY), an enzyme in the de novo lipogenesis pathway, as a novel LMW-E-interacting protein in the cytoplasm. LMW-E upregulated ACLY enzymatic activity, subsequently increasing lipid droplet formation, thereby providing cells with essential building blocks to support growth. ACLY was also required for LMW-E-mediated transformation, migration, and invasion of breast cancer cells in vitro along with tumor growth in vivo In clinical specimens of breast cancer, the absence of LMW-E and low expression of adipophilin (PLIN2), a marker of lipid droplet formation, associated with favorable prognosis, whereas overexpression of both proteins correlated with a markedly worse prognosis. Taken together, our findings establish a novel relationship between LMW-E isoforms of cyclin E and aberrant lipid metabolism pathways in breast cancer tumorigenesis, warranting further investigation in additional malignancies exhibiting their expression. Cancer Res; 76(8); 2406-18. ©2016 AACR. PMID:26928812

  9. [Intracytoplasmic lumina of benign and malignant breast diseases--a light and electron microscopic study].

    PubMed

    Gu, C M

    1990-07-01

    Intracytoplasmic lumina (ICLs) of 70 cases with breast carcinoma and 29 cases with benign breast diseases were observed by light and electron microscopy. ICLs were morphologically divided into two types. Type A was characterized by the presence of secretory materials stained with eosin in the lumen and Type B by the cytoplasmic vacuoles under light microscope. Electron microscopic observation on Type A ICLs showed numerous filiform microvilli projecting towards the lumen and various amounts of secretory materials in the lumen. Type B of ICLs only had scanty and short microvilli and rarely secretory materials in the lumen. The results indicated that: 1. The frequency of ICLs in breast cancer was significantly higher than that in benign breast disease (P less than 0.01). 2. The frequency of ICLs in breast cancer showed strong negative correlation with its histological grades but not with its histological types. 3. ICLs had similar frequency under both light and electron microscopes. As a relatively specific structure in breast carcinoma cells, ICLs may be helpful in the diagnosis of breast carcinoma and establishment of the breast origin for metastatic carcinoma. PMID:2176965

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

    SciTech Connect

    Ding, H; Zhao, B; Klopfer, M; Masaki, F; Baturin, P; Molloi, S

    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.

  11. Comparative biomechanical study of using decellularized human adipose tissues for post-mastectomy and post-lumpectomy breast reconstruction.

    PubMed

    Haddad, Seyyed M H; Omidi, Ehsan; Flynn, Lauren E; Samani, Abbas

    2016-04-01

    Developing suitable biomaterials for post-mastectomy or post-lumpectomy breast reconstruction is highly important. This study is aimed at evaluating biomechanical suitability of decellularized adipose tissue (DAT) for this purpose. The study involves computational experiments for evaluating deformation of the breast reconstructed using DAT under loading conditions pertaining to two common body position changes of prone-to-supine and prone-to-upright. This was conducted using nonlinear finite element models where the breast geometry was obtained from MRI image of a female breast. The experiments were performed using DAT sourced from various adipose tissue depots in comparison to natural adipose tissue. Data obtained from the conducted experiments showed no contour defects with various DAT materials for simulated post-mastectomy or post-lumpectomy breast reconstruction under the loading conditions. They also demonstrated that a breast reconstructed using DAT derived from the breast or subcutaneous abdominal depots exhibit significantly closer deformation, both qualitatively and quantitatively, to that of a normal breast under the same loading conditions. Similarity of DAT deformation to that of natural breast tissue in post-surgery breast reconstruction was assessed using nonlinear finite element analysis. Our results provide evidence that DAT derived from subcutaneous abdominal and breast depots yield more analogous deformation pattern to the natural tissue in post-mastectomy breast reconstruction applications. This is quite encouraging, as breast and subcutaneous adipose tissue can be readily obtained in large quantities from breast or abdominal lipo-reduction surgery procedures. Furthermore, in post-lumpectomy cases all DAT samples used in this research showed similar deformation, and thus are suitable as breast tissue substituents. PMID:26735182

  12. Strain elastography features of epidermoid tumours in superficial soft tissue: differences from other benign soft-tissue tumours and malignant tumours

    PubMed Central

    Park, H J; Lee, S M; Kim, W T; Lee, S; Ahn, K S

    2015-01-01

    Objective: We evaluated ultrasonographic features of superficial epidermoid tumour with a focus on strain elastography (SE) features that will help in the differential diagnosis of epidermoid tumour from other benign and malignant soft-tissue tumours. Methods: We retrospectively evaluated ultrasonographic and SE data of 103 surgically confirmed superficial soft-tissue tumours and tumour-like lesions: 29 cases of epidermoid tumour, 46 cases of other benign tumours and 28 cases of malignant tumour. SE and B-mode imaging were performed at the same time. SE characteristics were assigned into four grades (1–4) according to their elasticity. Interobserver agreement for the four SE scores between the two radiologists was analysed using kappa statistics. We classified each SE finding as a hard lesion (SE Score 3–4) or soft lesion (SE Score 1–2) and compared these findings using the χ2 test to identify whether a significant difference in mass hardness existed among epidermoid tumour, other benign tumour and malignant tumour. Results: Overall interobserver agreement according to the four SE scores was moderate (κ = 0.540), and overall agreement for the hardness [soft (Score 1–2) or hard (Score 3–4)] was almost perfect (κ = 0.825). Malignant tumours showed higher SE scores (3–4, hard nature) than did epidermoid tumour or other benign soft-tissue tumours. There were no differences in SE score between epidermoid tumour and other benign tumours. Conclusion: Superficial epidermoid tumour exhibits a softer nature than does malignant tumour but does not have a different SE pattern from other benign tumours. Advances in knowledge: SE features of epidermoid tumour might be helpful in differentiating from other benign and malignant tumours. PMID:25827206

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

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  15. Experimental implementation of coded aperture coherent scatter spectral imaging of cancerous and healthy breast tissue samples

    NASA Astrophysics Data System (ADS)

    Lakshmanan, Manu N.; Greenberg, Joel A.; Samei, Ehsan; Kapadia, Anuj J.

    2015-03-01

    A fast and accurate scatter imaging technique to differentiate cancerous and healthy breast tissue is introduced in this work. Such a technique would have wide-ranging clinical applications from intra-operative margin assessment to breast cancer screening. Coherent Scatter Computed Tomography (CSCT) has been shown to differentiate cancerous from healthy tissue, but the need to raster scan a pencil beam at a series of angles and slices in order to reconstruct 3D images makes it prohibitively time consuming. In this work we apply the coded aperture coherent scatter spectral imaging technique to reconstruct 3D images of breast tissue samples from experimental data taken without the rotation usually required in CSCT. We present our experimental implementation of coded aperture scatter imaging, the reconstructed images of the breast tissue samples and segmentations of the 3D images in order to identify the cancerous and healthy tissue inside of the samples. We find that coded aperture scatter imaging is able to reconstruct images of the samples and identify the distribution of cancerous and healthy tissues (i.e., fibroglandular, adipose, or a mix of the two) inside of them. Coded aperture scatter imaging has the potential to provide scatter images that automatically differentiate cancerous and healthy tissue inside of ex vivo samples within a time on the order of a minute.

  16. Differentiation of benign and malignant focal liver lesions: value of virtual touch tissue quantification of acoustic radiation force impulse elastography.

    PubMed

    Guo, Le-Hang; Wang, Shu-Jun; Xu, Hui-Xiong; Sun, Li-Ping; Zhang, Yi-Feng; Xu, Jun-Mei; Wu, Jian; Fu, Hui-Jun; Xu, Xiao-Hong

    2015-03-01

    The purpose of this study was to investigate the value of virtual tissue quantification (VTQ) of acoustic radiation force impulse elastography for the differential diagnosis of benign and malignant focal liver lesions (FLLs). Thus, a total of 134 FLLs in 134 patients were included. VTQ measurement was performed for each lesion in which the shear wave velocity (SWV) was measured. The difference in SWV and SWV ratio of FLL to surrounding liver between malignant and benign FLLs was evaluated, and the cutoff value was investigated. Receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic performance. A total of 134 lesions including 55 (41.0%) malignant FLLs and 79 (59.0%) benign ones were analyzed. The SWV of malignant and benign FLLs was 2.95 ± 1.00 m/s and 1.69 ± 0.89 m/s, respectively. Significant difference in SWV was presented between malignant and benign FLLs (p < 0.001). The SWV ratio of each FLL to the surrounding liver parenchyma was 1.83 ± 1.32 for malignant and 1.26 ± 0.78 for benign FLLs (p < 0.001). The area under the ROC curve in distinguishing malignant from benign lesions was 0.824 for SWV and 0.660 for SWV ratio. The cutoff value for differential diagnosis was 2.13 m/s for SWV and 1.37 for SWV ratio. The associated sensitivity and specificity were 83.3 and 77.9% for SWV and 59.6 and 77.3% for SWV ratio, respectively. In conclusion, VTQ provides quantitative stiffness information of FLLs and is helpful in the differential diagnosis between malignant and benign FLLs, particularly for the patients who are not candidates for contrast-enhanced imaging such as CT, MRI or contrast-enhanced ultrasound. PMID:25691297

  17. A morphometric approach in breast cytology--geometrical descriptors in the differentiation between benign and malignant lesions.

    PubMed

    Mihalache, Daniela; Giuşcă, Simona Eliza; Balan, Raluca; Amălinei, Cornelia; Grigoraş, Adriana; Căruntu, Irina Draga

    2014-01-01

    This study focuses on the analysis of geometric descriptors that can be applied in breast cytology, and their correlation with the qualitative features, with the aim to underline the differences between the benign and malignant cell profile. The morphometric investigation was performed on smears obtained by fine needle aspiration, 10 cases (group 1) diagnosed as benign and 10 cases (group 2) as malignant. For group 2, the malignancy was histopathologically confirmed on the surgical resection specimen. The sequence of automated operation, previously reported by us, permitted the extraction of the following geometrical descriptors: cytoplasmic area, nuclear area, nucleo-cytoplasmic ratio, equivalent diameter and form factor. We analyzed the differences between the benign and malignant morphometric features, and the correlation between the malignant morphometric features and cytological, respectively histological grading. Statistically significant difference in cytoplasmic areas, nuclear areas, value of nucleo-cytoplasmic ratio and equivalent diameter was noted between group I and II. For the form factor, we did not register statistically significant differences. For group 2, the correlation between the morphometric features and cytological grading revealed that the nuclear area is the most valuable descriptor, due to the significant differences between the three successive grades of cytological severity, followed by the cytoplasmic area and equivalent diameter, their numerical values presenting significant differences between cytological grade 1 and 3, and 2 and 3, respectively. The statistical analysis between the morphometric features and histological grading showed that nuclear area and equivalent diameter are the most viable indicators, due to the significant differences present between the three successive grades of pathologic severity, followed by cytoplasmic area (significant differences only for grade 2 versus 3) and for nucleo-cytoplasmic ratio (significant

  18. Tissue degeneration 7 years after breast augmentation with injected polyacrylamide hydrogel (PAAG).

    PubMed

    Xu, Chuanjun; Cao, Mo; Bao, Bing; Li, Huizheng; Yin, Dongyun

    2012-02-01

    Injectable polyacrylamide hydrogel (PAAG) is a jelly-like transparent implant used in breast augmentations. This type of implant had been used since 1998, but its use was prohibited in China in 2006 due to numerous complications that had arisen from its use. In one case, a rare appearance of PAAG tissue degeneration was observed 7 years after an injectable breast augmentation using PAAG. PMID:21717258

  19. Risk of Second Malignancies After Adjuvant Radiotherapy for Breast Cancer: A Large-Scale, Single-Institution Review

    SciTech Connect

    Kirova, Youlia M. . E-mail: youlia.kirova@curie.net; Gambotti, Laetitia; De Rycke, Yann; Vilcoq, Jacques R.; Asselain, Bernard; Fourquet, Alain

    2007-06-01

    Purpose: The aim of this study was to estimate the risk of second malignancies (SM) after radiation therapy (RT) for breast cancer (BC) in a large, institutional, homogeneous cohort of patients. Methods and Materials: We retrospectively studied 16,705 patients with nonmetastatic BC treated at the Institut Curie in Paris between 1981 and 1997. Adjuvant RT was given to 13,472 of these patients, and no RT was given to 3,233. The SM included all first nonBCs occurring during follow-up. Cumulative risks for each group were calculated using Kaplan-Meier estimates, censoring for contralateral cancer or death. Results: Median patient age at diagnosis of BC was 55 years for the whole population, and 53 and 60 years for patients who had and had not undergone irradiation, respectively. At the 10.5-year median follow-up, 709 patients were diagnosed with SM (113 in the non-RT and 596 in the RT group). There was a significant increase in the rate of sarcomas and lung cancers in the RT group compared with non-RT group (p 0.02). Treatment with RT was not found to increase the risk of other types of cancers such as thyroid cancer, malignant melanoma, gastrointestinal or genitourinary, and hematologic SM. Conclusions: This study suggests that adjuvant RT increased the rate of sarcomas and lung cancers, whereas it did not increase the rate of other malignancies.

  20. ADAM17 promotes breast cancer cell malignant phenotype through EGFR-PI3K-AKT activation

    PubMed Central

    Zheng, Xuguang; Jiang, Feng; Katakowski, Mark; Zhang, Zheng Gang; Lu, Qing-e; Chopp, Michael

    2009-01-01

    A disintegrin and metalloproteinase-17 (ADAM17) is involved in proteolytic ectodomain shedding of several membrane-bound growth factors and cytokines. The expression and activity of ADAM17 increase under some pathological conditions such as stroke and glioma. ADAM17 promotes neural progenitor cell migration and contributes to stroke-induced neurogenesis after stroke and brain tumor growth and invasion. In the present study, we sought to elucidate whether ADAM17 contributes to breast cancer progression and its mechanisms. To this end, we examined the role of ADAM17 in the proliferation, invasion, and tube formation of MDA-MB-231 breast cancer cells in vitro. Stable transfection of the MDA-MB-231 cell line with either a plasmid for over-expression of human ADAM17, or a siRNA to ADAM17 was employed in this study to establish high or low ADAM17 expression in breast cancer cells, respectively. For study of mechanism, the ADAM17 inhibitor TAPI-2 and the PI3K-AKT inhibitor LY294002 were used to counteract high ADAM17 expression or the activated PI3K-AKT pathway. Proliferation of MDA-MB-231 breast cancer cells were tested by MTT, Bromodeoxyuridine incorporation assay, growth curve, and sulforhodamine B assay. Matrigel invasion assays were used to assess the ability of MDA-MB-231 cells to penetrate the Extra Cellular Matrix. A Matrigel tube formation assay was performed to test capillary tube formation ability. EGFR-PI3K-Akt pathway activation in MDA-MB-231 cells under different ADAM17 expression levels were tested by Western blot and ELISA. Our data show that ADAM17 promotes the MDA-MB-231 malignant phenotype by increased proliferation, invasion and angiogenesis. TGF-α, VEGF secretion and VEGF expression was increasing by ADAM17 and counteracted by ADAM17 siRNA, TAPI-2, and LY294002 in MDA-MB-231 cells. ADAM17 activated, whereas ADAM17 siRNA, TAPI-2, and LY294002 deactivated the EGFR-PI3K-AKT signal pathway, which correlated with MDA-MB-231 cell malignant phenotype

  1. Suppression of Spry1 inhibits triple-negative breast cancer malignancy by decreasing EGF/EGFR mediated mesenchymal phenotype

    PubMed Central

    He, Qing; Jing, Hongyu; Liaw, Lucy; Gower, Lindsey; Vary, Calvin; Hua, Shucheng; Yang, Xuehui

    2016-01-01

    Sprouty (Spry) proteins have been implicated in cancer progression, but their role in triple-negative breast cancer (TNBC), a subtype of lethal and aggressive breast cancer, is unknown. Here, we reported that Spry1 is significantly expressed in TNBC specimen and MDA-MB-231 cells. To understand Spry1 regulation of signaling events controlling breast cancer phenotype, we used lentiviral delivery of human Spry1 shRNAs to suppress Spry1 expression in MDA-MB-231, an established TNBC cell line. Spry1 knockdown MDA-MB-231 cells displayed an epithelial phenotype with increased membrane E-cadherin expression. Knockdown of Spry1 impaired MDA-MB-231 cell migration, Matrigel invasion, and anchorage-dependent and -independent growth. Tumor xenografts originating from Spry1 knockdown MDA-MB-231 cells grew slower, had increased E-cadherin expression, and yielded fewer lung metastases compared to control. Furthermore, suppressing Spry1 in MDA-MB-231 cells impaired the induction of Snail and Slug expression by EGF, and this effect was associated with increased EGFR degradation and decreased EGFR/Grb2/Shp2/Gab1 signaling complex formation. The same phenotype was also observed in the TNBC cell line MDA-MB-157. Together, our results show that unlike in some tumors, where Spry may mediate tumor suppression, Spry1 plays a selective role in at least a subset of TNBC to promote the malignant phenotype via enhancing EGF-mediated mesenchymal phenotype. PMID:26976794

  2. Evolution of DNA aptamers for malignant brain tumor gliosarcoma cell recognition and clinical tissue imaging.

    PubMed

    Wu, Qiaoyi; Wu, Liang; Wang, Yuzhe; Zhu, Zhi; Song, Yanling; Tan, Yuyu; Wang, Xing-Fu; Li, Jiuxing; Kang, Dezhi; Yang, Chaoyong James

    2016-06-15

    Gliosarcoma, a variant of glioblastoma multiforme (GBM), is a highly invasive malignant tumor. Unfortunately, this disease still marked by poor prognosis regardless of modern treatments. It is of great significance to discover specific molecular probes targeting gliosarcoma for early cancer diagnosis and therapy. Herein, we have selected a group of DNA aptamers with high affinity and selectivity against gliosarcoma cells K308 using cell-SELEX. All the dissociation constants of these aptamers against gliosarcoma cells were in the nanomolar range and aptamer WQY-9 has the highest affinity and good selectivity among them. Furthermore, truncated aptamer sequence, WQY-9-B, shows similar recognition ability to aptamer WQY-9. In addition, WQY-9-B was found to be able to bind selectively and internalize into cytoplasm of target cancer cell at 37 °C. More importantly, compared to a random sequence, aptamer WQY-9-B showed excellent recognition rate (73.3%) for tissue sections of clinical gliosarcoma samples. These data suggests that aptamer WQY-9-B has excellent potential as an effective molecular probe for gliosarcoma diagnosis. PMID:26802746

  3. Demographic and Practice Characteristics of Pathologists Who Enjoy Breast Tissue Interpretation

    PubMed Central

    Oster, Natalia V.; Geller, Berta; Carney, Patricia A.; Reisch, Lisa M.; Onega, Tracy; Weaver, Donald L.; Frederick, Paul; Elmore, Joann G.

    2015-01-01

    Summary Physician attributes, job satisfaction and confidence in clinical skills are associated with enhanced performance and better patient outcomes. We surveyed 252 pathologists to evaluate associations between enjoyment of breast pathology, demographic/clinical characteristics and diagnostic performance. Diagnostic performance was determined by agreement with patient cases previously reviewed by a panel of experienced pathologists. Eighty-three percent of study participants reported enjoying breast pathology. Pathologists who enjoy breast interpretation were more likely to review ≥10 cases/week (p=0.003), report breast interpretation expertise (p=0.013), and high levels of confidence interpreting breast pathology (p<0.001). These pathologists were less likely to report that the field was challenging (p<0.001) and that breast cases make them more nervous than other types of pathology (p<0.001). Enjoyment was not associated with diagnostic performance. Millions of women undergo breast biopsy annually, thus it is reassuring that although nearly a fifth of practicing pathologists who interpret breast tissue report not enjoying the field, precision is not impacted. PMID:25554017

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

    SciTech Connect

    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.

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

    PubMed

    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. PMID:24614413

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

    NASA Astrophysics Data System (ADS)

    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.

  7. Ex vivo discrimination between normal and pathological tissues in human breast surgical biopsies using bioimpedance spectroscopy.

    PubMed

    Chauveau, N; Hamzaoui, L; Rochaix, P; Rigaud, B; Voigt, J J; Morucci, J P

    1999-04-20

    Ex vivo bioimpedance data measured on normal and cancerous female breast tissues are reported. They clearly show that the electrical properties of normal tissues, surrounding tissues, and carcinoma are different. These differences lie in the conductivity, in the characteristic frequency (frequency of the maximum of the imaginary part of the bioimpedance), and also in the shape of the Bode plots. Modeling using an R-S-Zcpe model is reported as well as indexes extracted from the real and imaginary parts of the bioimpedance. Even if a classification of the different types of tissues remains a difficult task and leads to much less precise diagnosis than microscopic examination, the electrical behavior of mammary tissue could be used to develop a noninvasive technique for early breast cancer detection. PMID:10372148

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

    NASA Astrophysics Data System (ADS)

    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.

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

    ClinicalTrials.gov

    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

  10. Circulating testosterone and prostate-specific antigen in nipple aspirate fluid and tissue are associated with breast cancer.

    PubMed Central

    Sauter, Edward R; Tichansky, David S; Chervoneva, Inna; Diamandis, Eleftherios P

    2002-01-01

    Preliminary evidence has associated testosterone and prostate-specific antigen (PSA) with breast cancer. Our objective was to determine whether a) testosterone levels in nipple aspirate fluid (NAF), serum, or breast tissue are associated with breast cancer; b) testosterone levels in serum are associated with levels in NAF; c) PSA in NAF, serum, or breast tissue is associated with breast cancer; and d) serum PSA is associated with NAF PSA levels. We obtained 342 NAF specimens from 171 women by means of a modified breast pump. Additionally, we collected 201 blood samples from 99 women and 51 tissue samples from 41 subjects who underwent surgical resection for suspected disease. Women currently using birth control pills or hormone replacement therapy were excluded from the study. Controlling for age and menopausal status, serum testosterone was significantly increased in women with breast cancer (p = 0.002). NAF and serum testosterone levels were not associated. Neither NAF nor tissue testosterone was associated with breast cancer. Controlling for menopausal status and age, NAF PSA was significantly decreased in women with breast cancer (p < 0.001). We did not find serum PSA to be associated with breast cancer, although we found an indication that, in postmenopausal women, its levels were lower in women with cancer. Serum PSA was associated with NAF PSA in postmenopausal women (p < 0.001). PSA levels in cancerous tissue were significantly lower than in benign breast specimens from subjects without cancer (p = 0.011), whereas levels of PSA in histologically benign specimens from subjects with cancer were intermediate. Our results suggest that serum testosterone is increased and NAF PSA is decreased in women with breast cancer, with PSA expression being higher in normal than in cancerous breast tissues. NAF and serum PSA levels in postmenopausal women are correlated, suggesting that as laboratory assessment of PSA becomes more sensitive, serum PSA may become useful in

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

    NASA Astrophysics Data System (ADS)

    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.

  12. Minimally Invasive and EX VIVO Diagnostics of Breast Cancer Tissue by Fiber Optic Evanescent Wave Fourier Transform Infrared (FEW-FTIR) Spectroscopy Method

    NASA Astrophysics Data System (ADS)

    Sokolov, Victor; Frank, George; Kolyakov, Sergei; Afanasyeva, Natalia; Bruch, Reinhard; Artujschenko, Slava

    1998-05-01

    Fiber Optic Evanescent Wave Fourier Transform Infrared (FEW-FTIR) spectroscopy using ultra sensitive fiber probes with low losses in the attenuated total reflection (ATR) regime in the middle infrared (MIR) region of the spectrum (850-1800 cm-1) was used for noninvasive and rapid (seconds) direct measurements of the spectra of normal and pathological breast tissue in vitro, ex vivo and in vivo. The aim of our studies is to perform accurate testing of tumor tissue at the early stages of their development. We have tested very small human samples (about 1mm) of normal and malignant tissue with fiber tip probes. As the first step we have performed a few experiments to optimize the fiber bending angle. In addition we are constructing and testing changeable tip probes for biopsy applications. Furthermore we are designing and creating needle probes for minimally invasive biopsy and fluid examinations.

  13. Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy.

    PubMed

    Rangel, M P; de Sá, V K; Martins, V; Martins, J R M; Parra, E R; Mendes, A; Andrade, P C; Reis, R M; Longatto-Filho, A; Oliveira, C Z; Takagaki, T; Carraro, D M; Nader, H B; Capelozzi, V L

    2015-06-01

    Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology. PMID:25992645

  14. Concentration Study of High Sensitive C - reactive Protein and some Serum Trace Elements in Patients with Benign and Malignant Breast Tumor

    PubMed Central

    Abdollahi, Alireza; Ali-Bakhshi, Abbas; Farahani, Zahra

    2015-01-01

    Background : Breast cancer is the most common invasive cancer in females worldwide. It accounts for 16% of all female cancers and 22.9% of invasive cancers in women. 18.2% of all cancer deaths worldwide including both males and females are from breast cancer. In this study we compared few serum elements in patients with benign and malignant breast tumor to find any related prognostic and predictive value. Subjects and Methods: A case-control study was carried out in a hospital (Tehran - Iran) in 2012. Target population was divided in 2 groups; subjects with benign and malignant breast tumors. We did preoperative hematological test. Five milliliter fasting blood vein was collected, centrifuged in 3000 g for 15 minutes to obtain serum. We measured serum Calcium (Ca), Phosphorus (P), Magnesium (Mg), Zinc (Zn), and high sensitive-CRP, analyzed statistically and compared recorded elements in 2 groups by software package SPSS version 16. The level of significant was considered P < 0.05. Results: Of 87 women, 49 cases with benign breast disease (group A) and 38 cases with breast cancer (group B) entered our study. Serum concentration of Ca, mg, and P in group A were higher than group B, however these differences were not significant. We found no significant correlation between serum Zn and type of tumor in our patients. On the other hand, a significant elevation in hs-CRP in patient with breast cancer was seen (P Value=.000). Conclusion : Our results have shown similar concentration of Ca, Mg, Zn, P and completely different hs-CRP concentration in patients with benign and malignant breast disease. PMID:26865928

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

    NASA Astrophysics Data System (ADS)

    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 <5%). Reliability studies compared measurements from four methods, 3DGRE, STIR, HSM, and MATH (N = 95 women) by linear regression and intra-class correlation (ICC) analyses. Rsqr, regression slopes, and ICC, respectively, were (1) 0.76-0.86, 0.8-1.1, and 0.87-0.92 for %-gland 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.

  16. Synchronous and Metachronous Breast Malignancies: A Cross-Sectional Retrospective Study and Review of the Literature

    PubMed Central

    Londero, Ambrogio P.; Bernardi, Sergio; Bertozzi, Serena; Angione, Vito; Gentile, Giuliana; Dri, Cinzia; Minucci, Antonio; Caponnetto, Filippo; Petri, Roberto

    2014-01-01

    Objective. There is increasing interest in patients with metachronous (MBC) and synchronous breast cancer (SBC). The objective of this study was to evaluate the occurrence and outcome of MBCs and SBCs. Methods. A retrospective study on women operated in our department for breast cancer between 2002 and 2005 was carried out. Patients were divided into three groups: women with MBC, SBC, and unilateral breast cancer (UBC). Moreover, we performed a meta-analysis of the English literature about multiple breast cancers between 2000 and 2011 taking into consideration their prevalence and overall survival (OS). Results. We identified 584 breast cancer patients: 16 women (3%) presented SBC and 40 MBC (7%, second cancer after 72-month follow-up IQR 40–145). Although the meta-analysis showed significant OS differences between MBC or SBC and UBC, we did not observe any significant OS difference among the three groups of our population. Anyway, we found a significant worse disease-free survival in MBC than UBC and a significant higher prevalence of radical surgery in MBC and SBC than UBC. Conclusions. Despite the low prevalence of MBC and SBC, the presence of a long time risk of MBC confirms the crucial role of ipsi- and contralateral mammographies in the postoperative follow-up. PMID:24877073

  17. Structural mass spectrometry of tissue extracts to distinguish cancerous and non-cancerous breast diseases

    PubMed Central

    Hines, K. M.; Ballard, B. R.

    2014-01-01

    Breast cancer is well-known to broadly impact cellular metabolism and aberrant metabolism in breast cancer tumors has been widely studied by both targeted and untargeted analyses to characterize the affected metabolic pathways. In this work, we utilize ultra-performance liquid chromatography (UPLC) in tandem with ion mobility-mass spectrometry (IM-MS), which provides chromatographic, structural, and mass information, to characterize the aberrant metabolism associated with breast diseases such as cancer. In a double-blind analysis of matched control (n=3) and disease tissues (n=3), tissues were homogenized, polar metabolites were extracted, and the extracts were characterized by UPLC-IM-MS/MS. Principle component analysis revealed a strong separation between disease tissues, with one diseased tissue clustering with the control tissues along PC1 and two others separated along PC2. Using postion mobility MS/MS spectra acquired by data-independent acquisition, the features giving rise to the observed grouping were determined to be biomolecules associated with aggressive breast cancer tumors, including glutathione, oxidized glutathione, thymosins β4 and β10, and choline-containing species. Pathology reports revealed the outlier of the disease tissues to be a benign fibroadenoma, whereas the other disease tissues represented highly metabolic benign and aggressive tumors. This IM-MS-based workflow bridges the transition from untargeted metabolomic profiling to tentative identifications of key descriptive molecular features using data acquired in one analysis, with additional experiments performed only for validation. The ability to resolve cancerous and non-cancerous tissues at the biomolecular level demonstrates UPLC-IM-MS/MS as a robust and sensitive platform for metabolomic profiling of tissues. PMID:25212505

  18. From milk to malignancy: the role of mammary stem cells in development, pregnancy and breast cancer

    PubMed Central

    Tiede, Benjamin; Kang, Yibin

    2011-01-01

    Adult stem cells of the mammary gland (MaSCs) are a highly dynamic population of cells that are responsible for the generation of the gland during puberty and its expansion during pregnancy. In recent years significant advances have been made in understanding how these cells are regulated during these developmentally important processes both in humans and in mice. Understanding how MaSCs are regulated is becoming a particularly important area of research, given that they may be particularly susceptible targets for transformation in breast cancer. Here, we summarize the identification of MaSCs, how they are regulated and the evidence for their serving as the origins of breast cancer. In particular, we focus on how changes in MaSC populations may explain both the increased risk of developing aggressive ER/PR(−) breast cancer shortly after pregnancy and the long-term decreased risk of developing ER/PR(+) tumors. PMID:21243011

  19. Expression of vimentin filaments in canine malignant mammary gland tumors: A simulation of clinicopathological features of human breast cancer.

    PubMed

    Rismanchi, Sanaz; Yadegar, Orly; Muhammadnejad, Samad; Amanpour, Saeid; Taghizadeh-Jahed, Masoud; Muhammadnejad, Ahad

    2014-09-01

    Canine malignant mammary gland tumors (CMMGTs) are the most common malignancies observed in females. Several biological similarities have been reported between CMMGTs and human breast cancer (HBC). The present study aimed to assess the correlation of vimentin filaments overexpression, as part of the process of epithelial-mesenchymal transition (EMT) and the clinicopathological characteristics in CMMGTs. The clinicopathological characteristics of 42 CMMGTs were collected. Paraffin-embedded blocks underwent immunohistochemistry staining, which was performed using vimentin (to assess the evolution of the EMT process), Ki-67 (for evaluation of tumor proliferation) and cluster of differentiation 34 (CD34) (for evaluation of angiogenesis) antibodies. The tumor stage, grade, vascular invasion, margin status, rate of expression of the vimentin filaments, microvessel density-CD34 and proliferation rate data were obtained. Finally, the association between the expression of the vimentin filaments and those parameters was resolved statistically. A significant association was shown between the overexpression of the vimentin filaments and tumor size (r=0.71, P=0.03), tumor grade (r=0.80, P=0.021), angiogenesis (r=0.57, P=0.043), proliferation coefficient (r=0.06, P=0.001) and vascular invasion (r=0.76, P=0.043). Vimentin overexpression did not statistically correlate with the tumor stage or the margin status. Similar to the findings of the present study, certain recent studies have indicated that vimentin filament expression in HBC and CMMGTs is associated with the severity of cancer. Thus, spontaneous canine mammary tumor models appear to be an appropriate animal model for breast cancer research, and the results of the present study could aid to reinforce the association. PMID:25054018

  20. Expression of vimentin filaments in canine malignant mammary gland tumors: A simulation of clinicopathological features of human breast cancer

    PubMed Central

    RISMANCHI, SANAZ; YADEGAR, ORLY; MUHAMMADNEJAD, SAMAD; AMANPOUR, SAEID; TAGHIZADEH-JAHED, MASOUD; MUHAMMADNEJAD, AHAD

    2014-01-01

    Canine malignant mammary gland tumors (CMMGTs) are the most common malignancies observed in females. Several biological similarities have been reported between CMMGTs and human breast cancer (HBC). The present study aimed to assess the correlation of vimentin filaments overexpression, as part of the process of epithelial-mesenchymal transition (EMT) and the clinicopathological characteristics in CMMGTs. The clinicopathological characteristics of 42 CMMGTs were collected. Paraffin-embedded blocks underwent immunohistochemistry staining, which was performed using vimentin (to assess the evolution of the EMT process), Ki-67 (for evaluation of tumor proliferation) and cluster of differentiation 34 (CD34) (for evaluation of angiogenesis) antibodies. The tumor stage, grade, vascular invasion, margin status, rate of expression of the vimentin filaments, microvessel density-CD34 and proliferation rate data were obtained. Finally, the association between the expression of the vimentin filaments and those parameters was resolved statistically. A significant association was shown between the overexpression of the vimentin filaments and tumor size (r=0.71, P=0.03), tumor grade (r=0.80, P=0.021), angiogenesis (r=0.57, P=0.043), proliferation coefficient (r=0.06, P=0.001) and vascular invasion (r=0.76, P=0.043). Vimentin overexpression did not statistically correlate with the tumor stage or the margin status. Similar to the findings of the present study, certain recent studies have indicated that vimentin filament expression in HBC and CMMGTs is associated with the severity of cancer. Thus, spontaneous canine mammary tumor models appear to be an appropriate animal model for breast cancer research, and the results of the present study could aid to reinforce the association. PMID:25054018

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

    PubMed

    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. PMID:25636590

  2. Quantitative Ultrasonic Evaluation of Radiation-Induced Late Tissue Toxicity: Pilot Study of Breast Cancer Radiotherapy

    SciTech Connect

    Liu Tian; Zhou Jun; Yoshida, Emi J.; Woodhouse, Shermian A.; Schiff, Peter B.; Wang, Tony J.C.; Lu Zhengfeng; Pile-Spellman, Eliza; Zhang Pengpeng; Kutcher, Gerald J.

    2010-11-01

    Purpose: To investigate the use of advanced ultrasonic imaging to quantitatively evaluate normal-tissue toxicity in breast-cancer radiation treatment. Methods and Materials: Eighteen breast cancer patients who received radiation treatment were enrolled in an institutional review board-approved clinical study. Radiotherapy involved a radiation dose of 50.0 to 50.4 Gy delivered to the entire breast, followed by an electron boost of 10.0 to 16.0 Gy delivered to the tumor bed. Patients underwent scanning with ultrasound during follow-up, which ranged from 6 to 94 months (median, 22 months) postradiotherapy. Conventional ultrasound images and radio-frequency (RF) echo signals were acquired from treated and untreated breasts. Three ultrasound parameters, namely, skin thickness, Pearson coefficient, and spectral midband fit, were computed from RF signals to measure radiation-induced changes in dermis, hypodermis, and subcutaneous tissue, respectively. Ultrasound parameter values of the treated breast were compared with those of the untreated breast. Ultrasound findings were compared with clinical assessment using Radiation Therapy Oncology Group (RTOG) late-toxicity scores. Results: Significant changes were observed in ultrasonic parameter values of the treated vs. untreated breasts. Average skin thickness increased by 27.3%, from 2.05 {+-} 0.22mm to 2.61 {+-} 0.52mm; Pearson coefficient decreased by 31.7%, from 0.41 {+-} 0.07 to 0.28 {+-} 0.05; and midband fit increased by 94.6%, from -0.92 {+-} 7.35 dB to 0.87 {+-} 6.70 dB. Ultrasound evaluations were consistent with RTOG scores. Conclusions: Quantitative ultrasound provides a noninvasive, objective means of assessing radiation-induced changes to the skin and subcutaneous tissue. This imaging tool will become increasingly valuable as we continue to improve radiation therapy technique.

  3. Quantifying adipose and fibroglandular breast tissue properties using MRI-guided NIR tomography

    NASA Astrophysics Data System (ADS)

    Brooksby, Ben; Srinivasan, Subhadra; Pogue, Brian W.; Jiang, Shudong; Dehghani, Hamid; Kogel, Christine; Weaver, John; Poplack, Steven P.; Pearlman, Justin D.; Paulsen, Keith D.

    2005-04-01

    Hybrid NIR-MRI imaging has been used in a clinical breast imaging system to characterize breast tissue properties. The multi-spectral, frequency-domain tomography system operates inside a clinical scanner via long silica-glass optical fiber bundles and using a non-magnetic fiber-patient interface attached to a high resolution MR breast coil. Sixteen fiber bundles are positioned around the circumference of the female breast yielding 240 measurements of light transmission (amplitude and phase) at six optical wavelengths from 660-850nm through up to 12 cm of tissue. From optical measurements, we use a Newton-type algorithm to reconstruct images of tissue optical properties (absorption and scattering), and physiological tissue features such as oxy-hemoglobin [Hb-O2], deoxy-hemoglobin concentrations [Hb-R], water concentration [water], scattering amplitude, and scattering power. We are exploring the synergistic benefits of a combined NIR-MRI data set, specifically the ways in which MRI (i.e. high spatial resolution) can be used to enhance NIR (i.e. high contrast resolution) image reconstruction. A priori knowledge can be applied to image reconstruction in the form of spatial and spectral constraints to improve spatial resolution, contrast, and quantitative accuracy of NIR images. In vivo results suggest that this combined system can accurately quantify contrast between the properties of tissues present in the breast (i.e. adipose and fibroglandular) regardless of their varied and complex spatial organization. For a group of healthy female volunteers, we observe greater contrast between the properties of adipose and glandular tissues when we use MR-guidance than when we do not, and values of total hemoglobin and water content are more consistent with what is physiologically expected.

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

    NASA Astrophysics Data System (ADS)

    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. Application of a GRNN oracle to the intelligent combination of several breast cancer benign/malignant predictive paradigms

    NASA Astrophysics Data System (ADS)

    Land, Walker H., Jr.; Masters, Timothy D.; Lo, Joseph Y.

    2000-06-01

    The General Regression Neural Network (GRNN) is well known to be an extremely effective prediction model in a wide variety of problems. It has been recently established that in many prediction problems, the results obtained by intelligently combining the outputs of several different prediction models are generally superior to the results obtained by using any one of the models. An overseer model that combines predictions from other independently trained prediction models is often called an oracle. This paper describes how the GRNN is modified to serve as a powerful oracle for combining decisions from four different breast cancer benign/malignant prediction models using mammogram data. Specifically, the GRNN oracle combines decisions from an evolutionary programming derived neural network, a probabilistic neural network, a fully- interconnected three-layer, feed-forward, error backpropagation network, and a linear discriminant analysis model. In all experiments conducted, the oracle consistently provided superior benign/malignant classification discrimination as measured by the receiver operator characteristic curve Az index values.

  6. Rates of upgrade to malignancy for 271 cases of flat epithelial atypia (FEA) diagnosed by breast core biopsy.

    PubMed

    Peres, Alexandre; Barranger, Emmanuel; Becette, Véronique; Boudinet, Alain; Guinebretiere, Jean-Marc; Cherel, Pascal

    2012-06-01

    Flat epithelial atypia (FEA) is a borderline lesion that might represent an early stage in the development of certain low-grade carcinomas in situ and invasive cancers. There are no guidelines on its management. Our objectives were to determine the upgrade to malignancy rate and identify a subpopulation of patients that might undergo just mammographic surveillance. We retrospectively reviewed the data for 271 FEA cases among 5,555 breast core biopsies obtained over a 7-year period (January 2003-2010). We collated clinical data (age, history of cancer, menopausal status), radiological data (lesion type, size, Bi-Rads category), technical data (number of biopsies, needle gauge, excision quality) and histological data and sought correlations between these factors and upgrade rate. The 271 FEA comprised 128 cases of pure FEA, 135 cases of FEA + atypical ductal hyperplasia, and 8 cases of FEA + atypical lobular hyperplasia. Overall, 184 patients underwent surgery and 46 mammographic surveillance. Surgery detected 34 cases of malignancy (23 CIS, 7 invasive cancers, and 4 mixed cases) giving a 15% upgrade rate. Quality of excision was the only factor associated with under-diagnosis. The presence of FEA at biopsy warrants surgery. PMID:22042365

  7. Modeling Malignant Breast Cancer Occurrence and Survival in Black and White Women

    ERIC Educational Resources Information Center

    Gleason, Michael

    2013-01-01

    Background: Breast cancer (BC), the most common cancer diagnosed in women in the United States, is a heterogeneous disease in which age-specific incidence rates (ASIRs) differ by race and mortality rates are higher in blacks than whites. Goals: (i) understand the reasons for the black-to-white ethnic crossover in the ASIRs; (ii) formulate a…

  8. Computer-Aided Diagnosis Scheme for Distinguishing Between Benign and Malignant Masses in Breast DCE-MRI.

    PubMed

    Honda, Emi; Nakayama, Ryohei; Koyama, Hitoshi; Yamashita, Akiyoshi

    2016-06-01

    Our purpose in this study was to develop a computer-aided diagnosis (CAD) scheme for distinguishing between benign and malignant breast masses in dynamic contrast material-enhanced magnetic resonance imaging (DCE-MRI). Our database consisted 90 DCE-MRI examinations, each of which contained four sequential phase images; this database included 28 benign masses and 62 malignant masses. In our CAD scheme, we first determined 11 objective features of masses by taking into account the image features and the dynamic changes in signal intensity that experienced radiologists commonly use for describing masses in DCE-MRI. Quadratic discriminant analysis (QDA) was employed to distinguish between benign and malignant masses. As the input of the QDA, a combination of four objective features was determined among the 11 objective features according to a stepwise method. These objective features were as follows: (i) the change in signal intensity from 2 to 5 min; (ii) the change in signal intensity from 0 to 2 min; (iii) the irregularity of the shape; and (iv) the smoothness of the margin. Using this approach, the classification accuracy, sensitivity, and specificity were shown to be 85.6 % (77 of 90), 87.1 % (54 of 62), and 82.1 % (23 of 28), respectively. Furthermore, the positive and negative predictive values were 91.5 % (54 of 59) and 74.2 % (23 of 31), respectively. Our CAD scheme therefore exhibits high classification accuracy and is useful in the differential diagnosis of masses in DCE-MRI images. PMID:26691512

  9. Spectroscopic Identification of Lipid, Protein and DNA Changes in Breast Cancer tissues

    NASA Astrophysics Data System (ADS)

    Badr, Y. A.; Hassab Elnaby, S. I.

    2007-02-01

    The FTIR spectroscopy, at the range 4000 - 6000 cm-1 showed a clear distinction between normal and cancer tissues. Normal tissues spectra contain a doublet structure at 4258 and 4332 cm-1. This structure is usually on top of a small band that extends from 3950 cm-1 to 4400 cm-1. This structure us also observed from pure lipid tissues from control patients. The origin of this structure could be attributed to combinations of lipid lines. This structure is completely absent in cancer tissues, instead a broad intense band appears from 5100 cm-1 to 5200 cm-1. The intensity of this band varies from one patient to another. The shape of this broad band indicates that it is the due to random orientation changes in the proteins. This band has a peak at 5164 cm-1, it contains another small kink at 4882 cm-1. This may lead also to the conclusion that this window band is associated with a short half life time energy levels. On The other hand the photoacoustic spectrum of the same tissues , shows that in normal tissues there are three very distinct peaks (namely 1097,1159 and 1232 cm-1) they disappear in malignant tissues and replaced by many weak ripples. Two peaks (1578, 1690 cm-1) changes their position in malignant tissues(1626, 1678 cm-1). A change in DNA markers was also noticed in the range 600-1700 cm-1.

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

    PubMed Central

    2016-01-01

    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.

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

    PubMed

    Rose, Jessica F; Zafar, Sarosh N; Ellsworth Iv, Warren A

    2016-01-01

    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. PMID:27190645

  12. Differentiation of Malignant and Benign Incidental Breast Lesions Detected by Chest Multidetector-Row Computed Tomography: Added Value of Quantitative Enhancement Analysis

    PubMed Central

    Lin, Yu-Pang; Hsu, Hsian-He; Ko, Kai-Hsiung; Chu, Chi-Ming; Chou, Yu-Ching; Chang, Wei-Chou; Chang, Tsun-Hou

    2016-01-01

    To retrospectively determine the association between breast lesion morphology and malignancy and to determine the optimal value of lesion enhancement (HU, Hounsfield units) to improve the diagnostic accuracy of breast cancer in patients with incidental breast lesions (IBLs). A total of 97 patients with 102 IBLs detected from July 2009 to December 2012 were enrolled in this study. Two radiologists analyzed CT images for the presence of malignancy based on the morphology of the lesions alone and in combination with an enhancement value (HU) analysis. There were 36 malignant and 66 benign IBLs. When the morphology and enhancement values were combined, the sensitivity, specificity, and accuracy were 92%, 97%, and 95%, respectively, for reader 1 and 89%, 94%, and 92%, respectively, for reader 2. The addition of HU values led to correct changes in the diagnosis; specifically, the accuracy of the diagnosis of reader 1 and reader 2 improved by 6.9% and 11.8%, respectively. The addition of the enhancement value (HU) to the CT morphology improved the diagnostic accuracy in the differentiation of malignant from benign IBLs by using the region of interest (ROI) to measure the HU within the most suspicious part of the lesion. PMID:27128524

  13. Automated breast tissue density assessment using high order regional texture descriptors in mammography

    NASA Astrophysics Data System (ADS)

    Law, Yan Nei; Lieng, Monica Keiko; Li, Jingmei; Khoo, David Aik-Aun

    2014-03-01

    Breast cancer is the most common cancer and second leading cause of cancer death among women in the US. The relative survival rate is lower among women with a more advanced stage at diagnosis. Early detection through screening is vital. Mammography is the most widely used and only proven screening method for reliably and effectively detecting abnormal breast tissues. In particular, mammographic density is one of the strongest breast cancer risk factors, after age and gender, and can be used to assess the future risk of disease before individuals become symptomatic. A reliable method for automatic density assessment would be beneficial and could assist radiologists in the evaluation of mammograms. To address this problem, we propose a density classification method which uses statistical features from different parts of the breast. Our method is composed of three parts: breast region identification, feature extraction and building ensemble classifiers for density assessment. It explores the potential of the features extracted from second and higher order statistical information for mammographic density classification. We further investigate the registration of bilateral pairs and time-series of mammograms. The experimental results on 322 mammograms demonstrate that (1) a classifier using features from dense regions has higher discriminative power than a classifier using only features from the whole breast region; (2) these high-order features can be effectively combined to boost the classification accuracy; (3) a classifier using these statistical features from dense regions achieves 75% accuracy, which is a significant improvement from 70% accuracy obtained by the existing approaches.

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

    PubMed

    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. PMID:25950862

  15. [In vitro sensitivity of breast cancer tissue to adriablastin in the presence and absence of estrogen receptors].

    PubMed

    Olinia, A Ia; Vitola, G Ia; Nuke, I Ia; Zeĭkate, G A; Emzin'sh, D E

    1984-01-01

    The report deals with a comparison of estrogen receptor concentration in tumor tissue of breast cancer patients and sensitivity of the said tissue to adriablastin in short-term organ cultures. No relationship was established between tumor tissue sensitivity to adriablastin and presence or absence of estrogen receptors. It is necessary to identify both the concentration of specific hormone receptors and individual sensitivity to chemotherapy in order to work out individually-tailored schemes of treatment of breast cancer patients. PMID:6710944

  16. HER2 Expression Beyond Breast Cancer: Therapeutic Implications for Gynecologic Malignancies

    PubMed Central

    English, Diana P.; Roque, Dana M.; Santin, Alessandro D.

    2013-01-01

    HER2 or ErbB2 is a member of the epidermal growth factor family and is overexpressed in subsets of breast, ovarian, gastric, colorectal, pancreatic and endometrial cancers. HER2 regulates signaling through several pathways (Ras/Raf/mitogen-activated protein kinase and phosphatidylinositol-3 kinase/protein kinase-B/mammalian target of rapamycin pathways) associated with cell survival and proliferation. HER2 overexpressed and/or gene amplified tumors are generally regarded as biologically aggressive neoplasms. In breast, cervical, endometrial and ovarian cancer, there have been several studies linking the amplification of the c-erbB2 gene with chemo-resistance and overall poor survival. Tyrosine kinase inhibitors and immunotherapy with monoclonal antibodies targeting HER2 holds promise for patients harboring these aggressive neoplasms. Trastuzumab combined with cytotoxic chemotherapy agents or conjugated with radioactive isotopes is currently being investigated in clinical trials of several tumor types. PMID:23529353

  17. A lectin-based approach to detecting carcinogenesis in breast tissue

    PubMed Central

    WI, GA RAM; MOON, BYUNG-IN; KIM, HYOUNG JIN; LIM, WOOSUNG; LEE, ANBOK; LEE, JUN WOO; KIM, HONG-JIN

    2016-01-01

    It has been suggested that the diversity of glycosylation structures that form during cancer progression and the sensitivity with which they are able to be detected have great potential for cancer screening. However, the large majority of breast cancer research has instead focused on the development of protein or nucleic acid markers. In the present study, alterations in glycosylation in breast cancer tissue were analyzed using enzyme-linked lectin assays (ELLAs), which have potential for high-throughput screening. Cancer tissues (CCs) and normal tissues (CNs) were collected from women with breast cancer ranging from stage 0 to IIIA. The specimens were divided into two groups, stage 0-I and stage II–III, and the levels of four types of lectin in stage 0-I and stage II–III CCs and CNs were compared by ELLA. The results demonstrated that, relative to CNs, the CCs contained significantly enhanced levels of mannosylation (stage 0-I, P<0.001; stage II–III, P<0.001), galactosylation (stage 0-I, P<0.05; stage II–III, P<0.001), sialylation (stage 0-I, P<0.001; stage II–III, P<0.01) and fucosylation (stage 0-I, P<0.01; stage II–III, P<0.01). Furthermore, stage II–III CCs had higher levels of mannosylation (P<0.05) and galactosylation (P<0.01) than stage 0-I CCs. The sensitivity of the ELLA system ranged from 71–100% when specificity was set at 100%. These results demonstrate that enhanced glycosylation levels identified by ELLA are associated with the development of breast tumors, and provide evidence of the exceptional sensitivity and specificity of the ELLA system in the detection of breast cancer. This approach is anticipated to contribute highly to the development of reliable diagnostic procedures for breast cancer. PMID:27313712

  18. Evaluation of discoidin domain receptor-2 (DDR2) expression level in normal, benign, and malignant human prostate tissues

    PubMed Central

    Azemikhah, Mitra; Ashtiani, Hamidreza Ahmadi; Aghaei, Mahmoud; Rastegar, Hosein

    2015-01-01

    Discoidin domain receptor (DDR) is a new member of the receptor tyrosine kinase family. There are two isoforms of discoidin domain receptor (DDR), DDR1 and DDR2. These receptors play a major role in the adhesion, motility and cell proliferation. Due to the important role of DDR2 in the development of tumor extension, this receptor is pivotal in the field of carcinogenesis. The aim of this study was to investigate the mRNA and protein expression of DDR2, in the malignant, benign prostatic hyperplasia (BPH) and normal tissues of patients with prostate cancer. In this study the gene and protein expression of DDR2 in adjacent normal (n=40), BPH (n=40), and malignant (n=40) prostate tissue were measured using real-time PCR and Western blotting. Then, the correlation of DDR2 gene and protein expression with prognostic factors such as age, tumor grade, tumor stage, lymph node involvement, and serum prostate-specific antigen (PSA) concentration were evaluated. The relative mRNA and protein expression level of DDR2 in malignant and benign prostate tissue was significantly higher than those of adjacent normal tissues (P<0.01). This expression was found to increase approximately 3.5 and 2.1 fold for mRNA and protein levels, respectively. Spearman test indicated a significant correlation between DDR2 mRNA and protein expression with prognostic factors such as tumor grade, stage, lymph node involvement, and serum PSA concentration. However, significant correlation with age was not observed. These findings suggest that DDR2 is a cancer-related gene associated with the aggressive progression of prostate cancer patients. PMID:26600862

  19. Evaluation of discoidin domain receptor-2 (DDR2) expression level in normal, benign, and malignant human prostate tissues.

    PubMed

    Azemikhah, Mitra; Ashtiani, Hamidreza Ahmadi; Aghaei, Mahmoud; Rastegar, Hosein

    2015-01-01

    Discoidin domain receptor (DDR) is a new member of the receptor tyrosine kinase family. There are two isoforms of discoidin domain receptor (DDR), DDR1 and DDR2. These receptors play a major role in the adhesion, motility and cell proliferation. Due to the important role of DDR2 in the development of tumor extension, this receptor is pivotal in the field of carcinogenesis. The aim of this study was to investigate the mRNA and protein expression of DDR2, in the malignant, benign prostatic hyperplasia (BPH) and normal tissues of patients with prostate cancer. In this study the gene and protein expression of DDR2 in adjacent normal (n=40), BPH (n=40), and malignant (n=40) prostate tissue were measured using real-time PCR and Western blotting. Then, the correlation of DDR2 gene and protein expression with prognostic factors such as age, tumor grade, tumor stage, lymph node involvement, and serum prostate-specific antigen (PSA) concentration were evaluated. The relative mRNA and protein expression level of DDR2 in malignant and benign prostate tissue was significantly higher than those of adjacent normal tissues (P<0.01). This expression was found to increase approximately 3.5 and 2.1 fold for mRNA and protein levels, respectively. Spearman test indicated a significant correlation between DDR2 mRNA and protein expression with prognostic factors such as tumor grade, stage, lymph node involvement, and serum PSA concentration. However, significant correlation with age was not observed. These findings suggest that DDR2 is a cancer-related gene associated with the aggressive progression of prostate cancer patients. PMID:26600862

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

    PubMed Central

    Abdullah Al-Dhabi, Naif; Srigopalram, Srisesharam; Ilavenil, Soundharrajan; Kim, Young Ock; Agastian, Paul; Baaru, Rajasekhar; Balamurugan, Kannan; Choi, Ki Choon; Valan Arasu, Mariadhas

    2016-01-01

    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. PMID:27110560

  1. Non-coding CK19 RNA in peripheral blood and tissue of breast cancer patients.

    PubMed

    Oloomi, Mana; Yardehnavi, Najmeh; Bouzari, Saeid; Moazzezy, Neda

    2013-01-01

    Breast carcinoma is the major cause of cancer-related death in women. The incidence of this carcinoma is rising and there are many attempts to decrease this problem. The aim of this study was detection of full-length cytokeratin 19 (CK19) mRNA, in peripheral blood and tissue of breast cancer patients in early stage of cancer. In this study, RT-PCR (reverse transcriptase-polymerase chain reaction) technique was used for detection of CK19 mRNA in peripheral blood and tissue of breast cancer patients. Primers were established to amplify the CK19 as a tumor marker. Moreover, CYFRA 21-1 subunit of CK19 protein was measured in the serum of patients. CK19 mRNA was detected and sequenced. It is shown that the most released CK19 mRNAs in blood and tissue of cancer patients are non-coding RNA. The mutated forms of mRNA are the incomplete transcripts of protein-coding gene as a long non-coding RNA (lncRNA) that could regulate gene expression. Moreover, small non-coding RNA (ncRNA) as fragments of CK19 is mostly observed in this experiment. They may play a role in tumorogenesis and their biologic exact function in breast cancer should be further elucidated. PMID:23585313

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

    PubMed

    Abdullah Al-Dhabi, Naif; Srigopalram, Srisesharam; Ilavenil, Soundharrajan; Kim, Young Ock; Agastian, Paul; Baaru, Rajasekhar; Balamurugan, Kannan; Choi, Ki Choon; Valan Arasu, Mariadhas

    2016-01-01

    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. PMID:27110560

  3. Evaluation of Tissue Sampling Methods Used for MRI-Detected Contralateral Breast Lesions in the American College of Radiology Imaging Network 6667 Trial

    PubMed Central

    DeMartini, Wendy B.; Hanna, Lucy; Gatsonis, Constantine; Mahoney, Mary C.; Lehman, Constance D.

    2013-01-01

    OBJECTIVE The purpose of our study was to evaluate tissue sampling methods used for MRI-detected suspicious contralateral breast lesions in the American College of Radiology Imaging Network (ACRIN) 6667 trial. MATERIALS AND METHODS Breast MRI was performed at 25 institutions in 969 women who had a recent diagnosis of unilateral breast cancer and negative contralateral mammography and clinical breast examinations. Biopsy was recommended for MRI findings in 135 women, and 121 underwent sampling. Frequencies and positive biopsy rates of sampling methods used for initial diagnosis and imaging guidance techniques were calculated and compared. RESULTS Sampling yielded 30 malignant and 91 benign results. Initial sampling used needle biopsy in 88 of 121 (72.7%) and surgical biopsy in 30 of 121 (24.8%) women. Surgical biopsy was excisional biopsy in 28 of 30 (93.3%) and mastectomy in two of 30 (6.7%). The remaining three of 121 (2.5%) women underwent mastectomy, but it was not documented whether this represented initial tissue sampling. Of imaging-guided procedures, 56 of 106 (52.8%) used MRI; 49 of 106 (46.2%), ultrasound; and one of 106 (1.0%), stereotaxis. MRI-guided sampling was with needle biopsy rather than wire-localized surgical biopsy in 33 of 56 (58.9%) women, whereas ultrasound used needle biopsy in 47 of 49 (95.9%). Positive biopsy rates of sampling methods were 20.5% for needle biopsy, 46.2% for excisional biopsy, and 0% for mastectomy. CONCLUSION The majority of initial biopsies for MRI-detected contralateral breast lesions used needle biopsy rather than surgical biopsy. Contralateral surgery could have been avoided in most cases had needle biopsy been performed because most excisional biopsy and all mastectomy results were benign. MRI-guided biopsy was significantly more likely than ultrasound-guided sampling to use wire-localized surgical biopsy rather than needle biopsy. PMID:22915431

  4. T 1 Relaxation Measurement of Ex-Vivo Breast Cancer Tissues at Ultralow Magnetic Fields

    PubMed Central

    Lee, Seong-Joo; Shim, Jeong Hyun; Kim, Kiwoong; Hwang, Seong-min; Yu, Kwon Kyu; Lim, Sanghyun; Han, Jae Ho; Yim, Hyunee; Kim, Jang-Hee; Jung, Yong Sik; Kim, Ku Sang

    2015-01-01

    We investigated T1 relaxations of ex-vivo cancer tissues at low magnetic fields in order to check the possibility of achieving a T1 contrast higher than those obtained at high fields. The T1 relaxations of fifteen pairs (normal and cancerous) of breast tissue samples were measured at three magnetic fields, 37, 62, and 122 μT, using our superconducting quantum interference device-based ultralow field nuclear magnetic resonance setup, optimally developed for ex-vivo tissue studies. A signal reconstruction based on Bayesian statistics for noise reduction was exploited to overcome the low signal-to-noise ratio. The ductal and lobular-type tissues did not exhibit meaningful T1 contrast values between normal and cancerous tissues at the three different fields. On the other hand, an enhanced T1 contrast was obtained for the mucinous cancer tissue. PMID:25705658

  5. Breast lump

    MedlinePlus

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

  6. Assembling a prototype resonance electrical impedance spectroscopy system for breast tissue signal detection: preliminary assessment

    NASA Astrophysics Data System (ADS)

    Sumkin, Jules; Zheng, Bin; Gruss, Michelle; Drescher, John; Leader, Joseph; Good, Walter; Lu, Amy; Cohen, Cathy; Shah, Ratan; Zuley, Margarita; Gur, David

    2008-03-01

    Using electrical impedance spectroscopy (EIS) technology to detect breast abnormalities in general and cancer in particular has been attracting research interests for decades. Large clinical tests suggest that current EIS systems can achieve high specificity (>= 90%) at a relatively low sensitivity ranging from 15% to 35%. In this study, we explore a new resonance frequency based electrical impedance spectroscopy (REIS) technology to measure breast tissue EIS signals in vivo, which aims to be more sensitive to small tissue changes. Through collaboration between our imaging research group and a commercial company, a unique prototype REIS system has been assembled and preliminary signal acquisition has commenced. This REIS system has two detection probes mounted in the two ends of a Y-shape support device with probe separation of 60 mm. During REIS measurement, one probe touches the nipple and the other touches to an outer point of the breast. The electronic system continuously generates sweeps of multi-frequency electrical pulses ranging from 100 to 4100 kHz. The maximum electric voltage and the current applied to the probes are 1.5V and 30mA, respectively. Once a "record" command is entered, multi-frequency sweeps are recorded every 12 seconds until the program receives a "stop recording" command. In our imaging center, we have collected REIS measurements from 150 women under an IRB approved protocol. The database includes 58 biopsy cases, 78 screening negative cases, and other "recalled" cases (for additional imaging procedures). We measured eight signal features from the effective REIS sweep of each breast. We applied a multi-feature based artificial neural network (ANN) to classify between "biopsy" and normal "non-biopsy" breasts. The ANN performance is evaluated using a leave-one-out validation method and ROC analysis. We conducted two experiments. The first experiment attempted to classify 58 "biopsy" breasts and 58 "non-biopsy" breasts acquired on 58 women

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

    PubMed Central

    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.

    2015-01-01

    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 <0.05. Gene expression microarray data was used to identify which of the BMI-associated methylation sites also showed correlation with gene expression. Gene set enrichment analysis was conducted to assess which pathways were enriched among the BMI-associated methylation sites. Of the 431,568 methylation sites analyzed, 2573 were associated with BMI (q value <0.05), 57 % of which showed an inverse correlation with BMI. Pathways enriched among the 2573 probe sites included those involved in inflammation, insulin receptor signaling, and leptin signaling. We were able to map 1251 of the BMI-associated methylation sites to gene expression data, and, of these, 226 (18 %) showed substantial correlations with gene expression. Our results suggest that BMI is associated with genome-wide methylation in non-diseased breast tissue and may influence epigenetic pathways involved in inflammatory and other carcinogenic processes. PMID:25953686

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

    PubMed

    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 <0.05. Gene expression microarray data was used to identify which of the BMI-associated methylation sites also showed correlation with gene expression. Gene set enrichment analysis was conducted to assess which pathways were enriched among the BMI-associated methylation sites. Of the 431,568 methylation sites analyzed, 2573 were associated with BMI (q value <0.05), 57 % of which showed an inverse correlation with BMI. Pathways enriched among the 2573 probe sites included those involved in inflammation, insulin receptor signaling, and leptin signaling. We were able to map 1251 of the BMI-associated methylation sites to gene expression data, and, of these, 226 (18 %) showed substantial correlations with gene expression. Our results suggest that BMI is associated with genome-wide methylation in non-diseased breast tissue and may influence epigenetic pathways involved in inflammatory and other carcinogenic processes. PMID:25953686

  9. ATR-FTIR spectroscopy coupled with chemometric analysis discriminates normal, borderline and malignant ovarian tissue: classifying subtypes of human cancer.

    PubMed

    Theophilou, Georgios; Lima, Kássio M G; Martin-Hirsch, Pierre L; Stringfellow, Helen F; Martin, Francis L

    2016-01-21

    Surgical management of ovarian tumours largely depends on their histo-pathological diagnosis. Currently, screening for ovarian malignancy with tumour markers in conjunction with radiological investigations has a low specificity for discriminating benign from malignant tumours. Also, pre-operative biopsy of ovarian masses increases the risk of intra-peritoneal dissemination of malignancy. Intra-operative frozen section, although sufficiently accurate in differentiating tumours according to their histological type, increases operation times. This results in increased surgery-related risks to the patient and additional burden to resource allocation. We set out to determine whether attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy, combined with chemometric analysis can be applied to discriminate between normal, borderline and malignant ovarian tumours and classify ovarian carcinoma subtypes according to the unique spectral signatures of their molecular composition. Formalin-fixed, paraffin-embedded ovarian tissue blocks were de-waxed, mounted on Low-E slides and desiccated before being analysed using ATR-FTIR spectroscopy. Chemometric analysis in the form of principal component analysis (PCA), successive projection algorithm (SPA) and genetic algorithm (GA), followed by linear discriminant analysis (LDA) of the obtained spectra revealed clear segregation between benign versus borderline versus malignant tumours as well as segregation between different histological tumour subtypes, when these approaches are used in combination. ATR-FTIR spectroscopy coupled with chemometric analysis has the potential to provide a novel diagnostic approach in the accurate diagnosis of ovarian tumours assisting surgical decision making to avoid under-treatment or over-treatment, with minimal impact to the patient. PMID:26090781

  10. “Ruptured” malignant phyllodes tumor of the breast: a case report

    PubMed Central

    Ditsatham, Chagkrit; Somwangprasert, Areewan; Watcharachan, Kirati; Wongmaneerung, Phanchaporn

    2016-01-01

    Phyllodes tumor or cystosarcoma phyllodes is a rare disease and is usually seen in middle-aged patients. Ruptured phyllodes tumor is a very rare condition. Our study reports patient presentation, diagnosis method, and treatment of an unusual case. A 58-year-old premenopausal female was diagnosed with a phyllodes tumor and presented with a rapidly growing mass for 2 months that ruptured 1 month later. She underwent simple mastectomy at the left side of her breast and received adjuvant radiotherapy. No recurrence was found 4 months after operation. PMID:26952179

  11. Diabetic Muscle Infarction of the Tibialis Anterior and Extensor Hallucis Longus Muscles Mimicking the Malignant Soft-Tissue Tumor

    PubMed Central

    Mimata, Yoshikuni; Sato, Kotaro; Tokunaga, Karen; Tsukimura, Itsuko; Tada, Hiroshi; Doita, Minoru

    2015-01-01

    One of the most common causes of skeletal muscle infarction is diabetic muscle infarction (DMI), a rare complication associated with poorly controlled diabetes. We report an atypical case of DMI localized in the tibialis anterior (TA) and extensor hallucis longus (EHL) muscles of an elderly individual. A 64-year-old man with type 2 diabetes mellitus presented with a 6-month history of a palpable mass in his lower left leg. Magnetic resonance imaging (MRI) revealed that the mass exhibited heterogeneous signals on T1- and T2-weighted images and slight heterogeneous enhancement within the muscles on fat suppressed T1-weighted images. Because histopathological analysis revealed mostly necrotic muscle tissues but no neoplastic cells, we resected the affected muscles. A typical symptom of DMI is severe abrupt-onset pain in the region of the affected muscles, but the patient did not complain of pain. Therefore, the diagnosis and treatment for DMI were delayed, and widespread irreversible muscle necrosis developed. MRI findings of DMI can be similar to that of a malignant soft-tissue tumor. So, it is necessary to consider the malignant soft-tissue tumor as one of the differential diagnoses of DMI. PMID:26236522

  12. Right Breast Mastectomy and Reconstruction with Tissue Expander under Thoracic Paravertebral Blocks in a 12-Week Parturient

    PubMed Central

    Webb, Christopher Allen-John; Weyker, Paul David; Cohn, Shara; Wheeler, Amanda; Lee, Jennifer

    2015-01-01

    Paravertebral blocks are becoming increasingly utilized for breast surgery with studies showing improved postoperative pain control, decreased need for opioids, and less nausea and vomiting. We describe the anesthetic management of an otherwise healthy woman who was 12 weeks pregnant presenting for treatment of her breast cancer. For patients undergoing breast mastectomy and reconstruction with tissue expanders, paravertebral blocks offer an anesthetic alternative when general anesthesia is not desired. PMID:26229692

  13. Definition of smad3 phosphorylation events that affect malignant and metastatic behaviors in breast cancer cells.

    PubMed

    Bae, Eunjin; Sato, Misako; Kim, Ran-Ju; Kwak, Mi-Kyung; Naka, Kazuhito; Gim, Jungsoo; Kadota, Mitsutaka; Tang, Binwu; Flanders, Kathleen C; Kim, Tae-Aug; Leem, Sun-Hee; Park, Taesung; Liu, Fang; Wakefield, Lalage M; Kim, Seong-Jin; Ooshima, Akira

    2014-11-01

    Smad3, a major intracellular mediator of TGFβ signaling, functions as both a positive and negative regulator in carcinogenesis. In response to TGFβ, the TGFβ receptor phosphorylates serine residues at the Smad3 C-tail. Cancer cells often contain high levels of the MAPK and CDK activities, which can lead to the Smad3 linker region becoming highly phosphorylated. Here, we report, for the first time, that mutation of the Smad3 linker phosphorylation sites markedly inhibited primary tumor growth, but significantly increased lung metastasis of breast cancer cell lines. In contrast, mutation of the Smad3 C-tail phosphorylation sites had the opposite effect. We show that mutation of the Smad3 linker phosphorylation sites greatly intensifies all TGFβ-induced responses, including growth arrest, apoptosis, reduction in the size of putative cancer stem cell population, epithelial-mesenchymal transition, and invasive activity. Moreover, all TGFβ responses were completely lost on mutation of the Smad3 C-tail phosphorylation sites. Our results demonstrate a critical role of the counterbalance between the Smad3 C-tail and linker phosphorylation in tumorigenesis and metastasis. Our findings have important implications for therapeutic intervention of breast cancer. PMID:25205100

  14. Simulation study of diffuse photon density waves traveling through normal and abnormal breast tissue

    NASA Astrophysics Data System (ADS)

    Deng, Xiaoyuan; Xing, Da

    1999-09-01

    Diffuse Photon Density Waves (DPDW) is new concept and principle, which takes advantage of the difference of absorption and scattering coefficients of different tissues to study the law of photon density fluctuation during a modulated light traveling through the tissues, thus to explore the structure and function of tissues. With the combination of image reconstruction technology, we can directly `visualize' the tissues. As a non- invasive exam, it has highly extensive applied prospect in medical field and brain cognition study. In this paper, the behavior of DPDW traveling through simulated breast tissue is tentatively examined. Under various conditions, we observed the characteristics of DPDW. We observed the reasonability of the distribution of sources and detectors, the factors that influence the distortion of DPDW. Simulation results could be used as a good theoretical guideline for experiments.

  15. Risk of second primary malignancies in women with breast cancer: Results from the European prospective investigation into cancer and nutrition (EPIC).

    PubMed

    Ricceri, Fulvio; Fasanelli, Francesca; Giraudo, Maria Teresa; Sieri, Sabina; Tumino, Rosario; Mattiello, Amalia; Vagliano, Liliana; Masala, Giovanna; Quirós, J Ramón; Travier, Noemie; Sánchez, María-José; Larranaga, Nerea; Chirlaque, María-Dolores; Ardanaz, Eva; Tjonneland, Anne; Olsen, Anja; Overvad, Kim; Chang-Claude, Jenny; Kaaks, Rudolf; Boeing, Heiner; Clavel-Chapelon, Françoise; Kvaskoff, Marina; Dossus, Laure; Trichopoulou, Antonia; Benetou, Vassiliki; Adarakis, George; Bueno-de-Mesquita, H B As; Peeters, Petra H; Sund, Malin; Andersson, Anne; Borgquist, Signe; Butt, Salma; Weiderpass, Elisabete; Skeie, Guri; Khaw, Kay-Tee; Travis, Ruth C; Rinaldi, Sabina; Romieu, Isabelle; Gunter, Marc; Kadi, Mai; Riboli, Elio; Vineis, Paolo; Sacerdote, Carlotta

    2015-08-15

    Women with a diagnosis of breast cancer are at increased risk of second primary cancers, and the identification of risk factors for the latter may have clinical implications. We have followed-up for 11 years 10,045 women with invasive breast cancer from a European cohort, and identified 492 second primary cancers, including 140 contralateral breast cancers. Expected and observed cases and Standardized Incidence Ratios (SIR) were estimated using Aalen-Johansen Markovian methods. Information on various risk factors was obtained from detailed questionnaires and anthropometric measurements. Cox proportional hazards regression models were used to estimate the role of risk factors. Women with breast cancer had a 30% excess risk for second malignancies (95% confidence interval-CI 18-42) after excluding contralateral breast cancers. Risk was particularly elevated for colorectal cancer (SIR, 1.71, 95% CI 1.43-2.00), lymphoma (SIR 1.80, 95% CI 1.31-2.40), melanoma (2.12; 1.63-2.70), endometrium (2.18; 1.75-2.70) and kidney cancers (2.40; 1.57-3.52). Risk of second malignancies was positively associated with age at first cancer, body mass index and smoking status, while it was inversely associated with education, post-menopausal status and a history of full-term pregnancy. We describe in a large cohort of women with breast cancer a 30% excess of second primaries. Among risk factors for breast cancer, a history of full-term pregnancy was inversely associated with the risk of second primary cancer. PMID:25650288

  16. NASA SMART Probe: Breast Cancer Application

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

  17. Second Malignancies After Adjuvant Radiation Therapy for Early Stage Breast Cancer: Is There Increased Risk With Addition of Regional Radiation to Local Radiation?

    SciTech Connect

    Hamilton, Sarah Nicole; Tyldesley, Scott; Li, Dongdong; Olson, Robert; McBride, Mary

    2015-04-01

    Purpose: This study was undertaken to determine whether there was an increased risk of second malignancies (SM), particularly lung cancer, in early stage breast cancer patients treated with the addition of nodal fields to breast and/or chest wall radiation therapy (RT). Materials and Methods: Subjects were stage I/II female breast cancer patients 20 to 79 years of age, diagnosed between 1989 and 2005 and treated with adjuvant RT at our institution. Patients were included if they survived and did not have SM within 3 years of diagnosis. Standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated to compare SM incidence to cancer incidence in the general sex- and age-matched populations. Secondary malignancy risks in patients treated with local RT (LRT) to the breast/chest wall were compared to those in patients treated with locoregional RT (LRRT) to the breast/chest wall and regional nodes, using multivariate regression analysis (MVA) to account for covariates. Results: The cohort included 12,836 patients with a median follow-up of 8.4 years. LRRT was used in 18% of patients. The SIR comparing patients treated with LRT to the general population was 1.29 (CI: 1.21-1.38). No statistically significant increased incidence of in-field malignancies (SIR, 1.04; CI: 0.87-1.23) and lung cancers (SIR, 1.06; CI: 0.88-1.26) was detected. The SIR comparing patients treated with LRRT to the general population was 1.39 (CI: 1.17-1.64). No statistically significant increased incidence of in-field malignancies (SIR, 1.26; CI: 0.77-1.94) and lung cancers (SIR, 1.27; CI: 0.76-1.98) was detected. On MVA comparing LRRT to LRT, the adjusted hazard ratio was 1.20 for in-field malignancies (CI: 0.68-2.16) and 1.26 for lung cancer (CI: 0.67-2.36). The excess attributable risk (EAR) to regional RT was 3.1 per 10,000 person years (CI: −8.7 to 9.9). Conclusions: No statistically significant increased risk of second malignancy was detected after LRRT relative to

  18. Chromogranin-reactive endocrine cells in argyrophilic carcinomas ("carcinoids") and normal tissue of the breast.

    PubMed Central

    Bussolati, G.; Gugliotta, P.; Sapino, A.; Eusebi, V.; Lloyd, R. V.

    1985-01-01

    Breast carcinomas, either positive or negative with the Grimelius' silver procedure, benign fibroadenomas, duct papillomas, and areas of histologically normal breast tissue were tested immunocytochemically with the mouse monoclonal antibody LK2H10 directed against human chromogranin. This is regarded as a general stain for polypeptide-hormone-producing cells and tumors. In 3 of the 9 cases of argyrophilic carcinoma, but in none of 12 ductal infiltrating carcinomas, chromogranin-positive cells were found: the number of reactive cells was very low in 1 case, while in the other 2 carcinomas about 50% of the argyrophilic cells appeared stained. In areas of histologically normal breast tissue, rare argyrophilic chromogranin-positive cells were detected. This study is the first reported evidence concerning the presence of endocrinelike cells probably belonging to the diffuse neuroendocrine system in the normal mammary parenchyma. Our data are consistent with the endocrine nature of at least some of the breast argyrophilic carcinomas. Images Figure 1 Figure 2 Figures 3 and 4 Figure 5 Figure 6 PMID:4025508

  19. Pedicled Breast Flap for Soft Tissue Coverage of a Forearm Blast Injury

    PubMed Central

    Zuriarrain, Alexander; Brooks, Christopher

    2016-01-01

    Summary: This article presents the case of a 35-year-old woman who sustained a shotgun blast injury to the left forearm and chest wall causing significant soft tissue loss of the extensor compartment. The patient suffered a Gustilo IIIB open radial shaft fracture requiring orthopedic stabilization and plastic surgery intervention. As a result, the patient eventually was reconstructed with the use of a pedicled breast flap. Because of the patient’s macromastia and her large forearm wound and morbid obesity, an individualized approach was developed such that a breast flap was designed because of its proximity to the upper extremity. The advantage of this type of reconstruction is a more natural contour to the forearm with minimal donor site morbidity. Before creation of the flap, the patient expressed interest in a reduction mammaplasty because of her symptomatic macromastia. Overall, this was a 2-step operation whereby first the breast flap was created, and then a few weeks later, once the arm healed, the reduction mammaplasty was performed. Other types of flaps for upper extremity reconstruction include the rectus abdominis myocutaneous, transverse rectus abdominis myocutaneous, vertical rectus abdominis myocutaneous, groin, and latissumus dorsi. The pedicled breast flap is an innovative approach to upper extremity soft tissue coverage and can be tailored to the specific needs of patients similar to our case presentation. PMID:27104108

  20. Optical properties of normal and diseased breast tissues: prognosis for optical mammography

    NASA Astrophysics Data System (ADS)

    Troy, Tamara L.; Page, David L.; Sevick-Muraca, Eva M.

    1996-07-01

    The use of near-infrared measurements of photon migration has been recently demonstrated for the detection of breast cancer in Europe. Yet the clinical success of this potential screening tool depends upon consistent detection of the disease at earlier stages than is currently possible with conventional x-ray mammography. In this paper, we present the optical property measurements of 115 histologically classified breast tissue specimens in order to determine whether consistent and significant optical contrast exists for detection of the disease. Our in vitro optical properties measured with a double integrating sphere technique show consistent changes in effective scattering coefficients, (mu) s', with tissue classification of infiltrating carcinoma, ductal carcinoma in situ, mucinous carcinoma, normal fatty, and normal fibrous tissues. However, there is little change in the in vitro tissue absorption coefficient, (mu) a, measured at 749, 789, and 836 nm. For normal and diseased tissue specimens extracted from the same patient, we found differences in optical properties, indicating optical contrast. Using a finite- element prediction of light propagation, we evaluated this optical contrast for photon migration detection of ductal carcinoma in situ tissues using these optical properties measured in vitro.

  1. Measurement of breast-tissue x-ray attenuation by spectral mammography: solid lesions.

    PubMed

    Fredenberg, Erik; Kilburn-Toppin, Fleur; Willsher, Paula; Moa, Elin; Danielsson, Mats; Dance, David R; Young, Kenneth C; Wallis, Matthew G

    2016-04-01

    Knowledge of x-ray attenuation is essential for developing and evaluating x-ray imaging technologies. For instance, techniques to distinguish between cysts and solid tumours at mammography screening would be highly desirable to reduce recalls, but the development requires knowledge of the x-ray attenuation for cysts and tumours. We have previously measured the attenuation of cyst fluid using photon-counting spectral mammography. Data on x-ray attenuation for solid breast lesions are available in the literature, but cover a relatively wide range, likely caused by natural spread between samples, random measurement errors, and different experimental conditions. In this study, we have adapted a previously developed spectral method to measure the linear attenuation of solid breast lesions. A total of 56 malignant and 5 benign lesions were included in the study. The samples were placed in a holder that allowed for thickness measurement. Spectral (energy-resolved) images of the samples were acquired and the image signal was mapped to equivalent thicknesses of two known reference materials, which can be used to derive the x-ray attenuation as a function of energy. The spread in equivalent material thicknesses was relatively large between samples, which is likely to be caused mainly by natural variation and only to a minor extent by random measurement errors and sample inhomogeneity. No significant difference in attenuation was found between benign and malignant solid lesions. The separation between cyst-fluid and tumour attenuation was, however, significant, which suggests it may be possible to distinguish cystic from solid breast lesions, and the results lay the groundwork for a clinical trial. In addition, the study adds a relatively large sample set to the published data and may contribute to a reduction in the overall uncertainty in the literature. PMID:26961507

  2. Measurement of breast-tissue x-ray attenuation by spectral mammography: solid lesions

    NASA Astrophysics Data System (ADS)

    Fredenberg, Erik; Kilburn-Toppin, Fleur; Willsher, Paula; Moa, Elin; Danielsson, Mats; Dance, David R.; Young, Kenneth C.; Wallis, Matthew G.

    2016-04-01

    Knowledge of x-ray attenuation is essential for developing and evaluating x-ray imaging technologies. For instance, techniques to distinguish between cysts and solid tumours at mammography screening would be highly desirable to reduce recalls, but the development requires knowledge of the x-ray attenuation for cysts and tumours. We have previously measured the attenuation of cyst fluid using photon-counting spectral mammography. Data on x-ray attenuation for solid breast lesions are available in the literature, but cover a relatively wide range, likely caused by natural spread between samples, random measurement errors, and different experimental conditions. In this study, we have adapted a previously developed spectral method to measure the linear attenuation of solid breast lesions. A total of 56 malignant and 5 benign lesions were included in the study. The samples were placed in a holder that allowed for thickness measurement. Spectral (energy-resolved) images of the samples were acquired and the image signal was mapped to equivalent thicknesses of two known reference materials, which can be used to derive the x-ray attenuation as a function of energy. The spread in equivalent material thicknesses was relatively large between samples, which is likely to be caused mainly by natural variation and only to a minor extent by random measurement errors and sample inhomogeneity. No significant difference in attenuation was found between benign and malignant solid lesions. The separation between cyst-fluid and tumour attenuation was, however, significant, which suggests it may be possible to distinguish cystic from solid breast lesions, and the results lay the groundwork for a clinical trial. In addition, the study adds a relatively large sample set to the published data and may contribute to a reduction in the overall uncertainty in the literature.

  3. Differences of photodamage in various malignant tissues which appear after application of photodynamic therapy using different laser systems

    NASA Astrophysics Data System (ADS)

    Bloznelyte-Plesniene, Laima; Garlaite, Deiva; Felinskaite, Eulalija; Ponomarev, Igor V.

    1995-05-01

    From 1989 to 1994 more than 600 various malignant foci were treated by more than 400 courses of PDT in the Lithuanian Oncology Center. During the application of PDT we used the following lasers: 35 MW He-Ne laser with 630-1 nm wavelength; 100-300 MW dye lasers with a wavelength of 629-3 nm, and a 100- 300 MW gold vapor laser, with a wavelength of 629-1 nm. We noticed some differences in results between the low-power lasers and the high-energy lasers. The initial response was better in patients whose tumors were irradiated with high-energy lasers, but the was more recidivism in this group. The most interesting thin we noticed was that there were significant differences in response of tumors of various histogenesis. for example, in most cases there was full necrosis of basal cell carcinoma immediately after PDT, but there were only some necrobiotical changes at the same time in other malignant tissues. Full necrosis in squamous cell cancer was noticed ont he third to fourth day after PDT. Full necrosis of malignant melanoma was noticed on the fifth to tenth day after PDT. It is important to emphasize that full melanoma necrosis was more frequently observed in cases where the low-power He-Ne laser was used for the PDT.

  4. Tissue-specific Co-expression of Long Non-coding and Coding RNAs Associated with Breast Cancer

    PubMed Central

    Wu, Wenting; Wagner, Erin K.; Hao, Yangyang; Rao, Xi; Dai, Hongji; Han, Jiali; Chen, Jinhui; Storniolo, Anna Maria V.; Liu, Yunlong; He, Chunyan

    2016-01-01

    Inference of the biological roles of lncRNAs in breast cancer development remains a challenge. Here, we analyzed RNA-seq data in tumor and normal breast tissue samples from 18 breast cancer patients and 18 healthy controls and constructed a functional lncRNA-mRNA co-expression network. We revealed two distinctive co-expression patterns associated with breast cancer, reflecting different underlying regulatory mechanisms: (1) 516 pairs of lncRNA-mRNAs have differential co-expression pattern, in which the correlation between lncRNA and mRNA expression differs in tumor and normal breast tissue; (2) 291 pairs have dose-response co-expression pattern, in which the correlation is similar, but the expression level of lncRNA or mRNA differs in the two tissue types. We further validated our findings in TCGA dataset and annotated lncRNAs using TANRIC. One novel lncRNA, AC145110.1 on 8p12, was found differentially co-expressed with 127 mRNAs (including TOX4 and MAEL) in tumor and normal breast tissue and also highly correlated with breast cancer clinical outcomes. Functional enrichment and pathway analyses identified distinct biological functions for different patterns of co-expression regulations. Our data suggested that lncRNAs might be involved in breast tumorigenesis through the modulation of gene expression in multiple pathologic pathways. PMID:27597120

  5. Tissue-specific Co-expression of Long Non-coding and Coding RNAs Associated with Breast Cancer.

    PubMed

    Wu, Wenting; Wagner, Erin K; Hao, Yangyang; Rao, Xi; Dai, Hongji; Han, Jiali; Chen, Jinhui; Storniolo, Anna Maria V; Liu, Yunlong; He, Chunyan

    2016-01-01

    Inference of the biological roles of lncRNAs in breast cancer development remains a challenge. Here, we analyzed RNA-seq data in tumor and normal breast tissue samples from 18 breast cancer patients and 18 healthy controls and constructed a functional lncRNA-mRNA co-expression network. We revealed two distinctive co-expression patterns associated with breast cancer, reflecting different underlying regulatory mechanisms: (1) 516 pairs of lncRNA-mRNAs have differential co-expression pattern, in which the correlation between lncRNA and mRNA expression differs in tumor and normal breast tissue; (2) 291 pairs have dose-response co-expression pattern, in which the correlation is similar, but the expression level of lncRNA or mRNA differs in the two tissue types. We further validated our findings in TCGA dataset and annotated lncRNAs using TANRIC. One novel lncRNA, AC145110.1 on 8p12, was found differentially co-expressed with 127 mRNAs (including TOX4 and MAEL) in tumor and normal breast tissue and also highly correlated with breast cancer clinical outcomes. Functional enrichment and pathway analyses identified distinct biological functions for different patterns of co-expression regulations. Our data suggested that lncRNAs might be involved in breast tumorigenesis through the modulation of gene expression in multiple pathologic pathways. PMID:27597120

  6. Altered features and increased chemosensitivity of human breast cancer cells mediated by adipose tissue-derived mesenchymal stromal cells

    PubMed Central

    2013-01-01

    Background Mesenchymal stromal cells (MSCs) represent heterogeneous cell population suitable for cell therapies in regenerative medicine. MSCs can also substantially affect tumor biology due to their ability to be recruited to the tumor stroma and interact with malignant cells via direct contacts and paracrine signaling. The aim of our study was to characterize molecular changes dictated by adipose tissue-derived mesenchymal stromal cells (AT-MSCs) and the effects on drug responses in human breast cancer cells SKBR3. Methods The tumor cells were either directly cocultured with AT-MSCs or exposed to MSCs-conditioned medium (MSC-CM). Changes in cell biology were evaluated by kinetic live cell imaging, fluorescent microscopy, scratch wound assay, expression analysis, cytokine secretion profiling, ATP-based viability and apoptosis assays. The efficiency of cytotoxic treatment in the presence of AT-MSCs or MSCs-CM was analyzed. Results The AT-MSCs altered tumor cell morphology, induced epithelial-to-mesenchymal transition, increased mammosphere formation, cell confluence and migration of SKBR3. These features were attributed to molecular changes induced by MSCs-secreted cytokines and chemokines in breast cancer cells. AT-MSCs significantly inhibited the proliferation of SKBR3 cells in direct cocultures which was shown to be dependent on the SDF-1α/CXCR4 signaling axis. MSC-CM-exposed SKBR3 or SKBR3 in direct coculture with AT-MSCs exhibited increased chemosensitivity and induction of apoptosis in response to doxorubicin and 5-fluorouracil. Conclusions Our work further highlights the multi-level nature of tumor-stromal cell interplay and demonstrates the capability of AT-MSCs and MSC-secreted factors to alter the anti-tumor drug responses. PMID:24209831

  7. Content of low density lipoprotein receptors in breast cancer tissue related to survival of patients.

    PubMed Central

    Rudling, M J; Ståhle, L; Peterson, C O; Skoog, L

    1986-01-01

    The content of low density lipoprotein (LDL) receptors in tissue from primary breast cancers was determined and its prognostic information compared with that of variables of established prognostic importance. Frozen tumour specimens were selected, and tissue from 72 patients (32 of whom had died) were studied. The LDL receptor content showed an inverse correlation with the survival time. Analysis by a multivariate statistical method showed that the presence of axillary metastasis, content of receptors for oestrogen and LDL, diameter of the tumour, and DNA pattern were all of prognostic value with regard to patient survival. Improved methods of predicting survival time in patients with breast cancer may be of value in the choice of treatment for individual patients. PMID:3081176

  8. A new test phantom with different breast tissue compositions for image quality assessment in conventional and digital mammography

    NASA Astrophysics Data System (ADS)

    Pachoud, Marc; Lepori, D.; Valley, Jean-François; Verdun, Francis R.

    2004-12-01

    Our objective is to describe a new test phantom that permits the objective assessment of image quality in conventional and digital mammography for different types of breast tissue. A test phantom, designed to represent a compressed breast, was made from tissue equivalent materials. Three separate regions, with different breast tissue compositions, are used to evaluate low and high contrast resolution, spatial resolution and image noise. The phantom was imaged over a range of kV using a Contour 2000 (Bennett) mammography unit with a Kodak MinR 2190-MinR L screen film combination and a Senograph 2000D (General Electric) digital mammography unit. Objective image quality assessments for different breast tissue compositions were performed using the phantom for conventional and digital mammography. For a similar mean glandular dose (MGD), the digital system gives a significantly higher contrast-to-noise ratio (CNR) than the screen film system for 100% glandular tissue. In conclusion, in mammography, a range of exposure conditions is used for imaging because of the different breast tissue compositions encountered clinically. Ideally, the patient dose image quality relationship should be optimized over the range of exposure conditions. The test phantom presented in this work permits image quality parameters to be evaluated objectively for three different types of breast tissue. Thus, it is a useful tool for optimizing the patient dose image quality relationship.

  9. miRNA expression patterns in normal breast tissue and invasive breast cancers of BRCA1 and BRCA2 germ-line mutation carriers

    PubMed Central

    Vos, Shoko; Vesuna, Farhad; Raman, Venu; van Diest, Paul J.; van der Groep, Petra

    2015-01-01

    miRNA deregulation has been found to promote carcinogenesis. Little is known about miRNA deregulation in hereditary breast tumors as no miRNA expression profiling studies have been performed in normal breast tissue of BRCA1 and BRCA2 mutation carriers. miRNA profiles of 17 BRCA1- and 9 BRCA2-associated breast carcinomas were analyzed using microarrays. Normal breast tissues from BRCA1 and BRCA2 mutation carriers (both n = 5) and non-mutation carriers (n = 10) were also included. Candidate miRNAs were validated by qRT-PCR. Breast carcinomas showed extensive miRNA alteration compared to normal breast tissues in BRCA1 and BRCA2 mutation carriers. Moreover, normal breast tissue from BRCA1 mutation carriers already showed miRNA alterations compared to non-mutation carriers. Chromosomal distribution analysis showed several hotspots containing down- or up-regulated miRNAs. Pathway analysis yielded many similarities between the BRCA1 and BRCA2 axes with miRNAs involved in cell cycle regulation, proliferation and apoptosis. Lesser known pathways were also affected, including cellular movement and protein trafficking. This study provides a comprehensive insight into the potential role of miRNA deregulation in BRCA1/2-associated breast carcinogenesis. The observed extensive miRNA deregulation is likely the result of genome-wide effects of chromosomal instability caused by impaired BRCA1 or BRCA2 function. This study's results also suggest the existence of common pathways driving breast carcinogenesis in both BRCA1 and BRCA2 germ-line mutation carriers. PMID:26378051

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

    PubMed

    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. PMID:27213669

  11. Lipid peroxidation, antioxidant concentrations, and fatty acid contents of muscle tissue from malignant hyperthermia-susceptible swine.

    PubMed

    Duthie, G G; Wahle, K W; Harris, C I; Arthur, J R; Morrice, P C

    1992-08-01

    Homogenates of semitendinosus muscle from malignant hyperthermia (MH)-susceptible pigs produced threefold more pentane than those from MH-resistant pigs, indicating enhanced free radical-mediated peroxidation of n-6 fatty acids. This did not reflect a deficiency in tissue antioxidants or antioxidant-enzymes but glutathione concentrations and glutathione peroxidase activities were increased in the tissue from MH-susceptible swine, consistent with an adaptive response to a sustained oxidant stress. A lower proportion of linoleic acid (18:2 n-6) in phospholipids and neutral lipids in muscle from MHS pigs indicated increased peroxidation or metabolism (desaturation and elongation). The increased oleic acid (18:1 n-9) in the MHS muscle indicated that desaturase activity was elevated in all lipid classes. The results are consistent with the hypothesis that enhanced free radical activity and lipid peroxidation contributes to the abnormalities in Ca2+ homeostasis and polyunsaturated fatty acid metabolism in MH. PMID:1632646

  12. Analysis of HOX gene expression patterns in human breast cancer.

    PubMed

    Hur, Ho; Lee, Ji-Yeon; Yun, Hyo Jung; Park, Byeong Woo; Kim, Myoung Hee

    2014-01-01

    HOX genes are highly conserved transcription factors that determine the identity of cells and tissues along the anterior-posterior body axis in developing embryos. Aberrations in HOX gene expression have been shown in various tumors. However, the correlation of HOX gene expression patterns with tumorigenesis and cancer progression has not been fully characterized. Here, to analyze putative candidate HOX genes involved in breast cancer tumorigenesis and progression, the expression patterns of 39 HOX genes were analyzed using breast cancer cell lines and patient-derived breast tissues. In vitro analysis revealed that HOXA and HOXB gene expression occurred in a subtype-specific manner in breast cancer cell lines, whereas most HOXC genes were strongly expressed in most cell lines. Among the 39 HOX genes analyzed, 25 were chosen for further analysis in malignant and non-malignant tissues. Fourteen genes, encoding HOXA6, A13, B2, B4, B5, B6, B7, B8, B9, C5, C9, C13, D1, and D8, out of 25 showed statistically significant differential expression patterns between non-malignant and malignant breast tissues and are putative candidates associated with the development and malignant progression of breast cancer. Our data provide a valuable resource for furthering our understanding of HOX gene expression in breast cancer and the possible involvement of HOX genes in tumor progression. PMID:23820980

  13. Quantification of effects of cancer on elastic properties of breast tissue by Atomic Force Microscopy.

    PubMed

    Ansardamavandi, Arian; Tafazzoli-Shadpour, Mohammad; Omidvar, Ramin; Jahanzad, Iisa

    2016-07-01

    Different behaviors of cells such as growth, differentiation and apoptosis widely differ in case of diseases. The mechanical properties of cells and tissues can be used as a clue for diagnosis of pathological conditions. Here, we implemented Atomic Force Microscopy to evaluate the extent of alteration in mechanical stiffness of tissue layers from patients affected by breast cancer and investigated how data can be categorized based on pathological observations. To avoid predefined categories, Fuzzy-logic algorithm as a novel method was used to divide and categorize the derived Young׳s modulus coefficients (E). Such algorithm divides data among groups in such way that data of each group are mostly similar while dissimilar with other groups. The algorithm was run for different number of categories. Results showed that three (followed by two with small difference) groups categorized data best. Three categories were defined as (E<3000Pa, 30007000Pa) among which data were allocated. The first cluster was assumed as the cellular region while the last cluster was referred to the fibrous parts of the tissue. The intermediate region was due to other non-cellular parts. Results indicated 50% decline of average Young׳s modulus of cellular region of cancerous tissues compared to healthy tissues. The average Young׳s modulus of non-cellular area of normal tissues was slightly lower than that of cancerous tissues, although the difference was not statistically different. Through clustering, the measured Young׳s moduli of different locations of cancerous tissues, a quantified approach was developed to analyze changes in elastic modulus of a spectrum of components of breast tissue which can be applied in diagnostic mechanisms of cancer development, since in cancer progression the softening cell body facilitates the migration of cancerous cells through the original tumor and endothelial junctions. PMID:26878463

  14. Mammary tissue microenvironment determines T cell-dependent breast cancer-associated inflammation.

    PubMed

    Takahashi, Kei; Nagai, Nao; Ogura, Keisuke; Tsuneyama, Koichi; Saiki, Ikuo; Irimura, Tatsuro; Hayakawa, Yoshihiro

    2015-07-01

    Although the importance of the host tissue microenvironment in cancer progression and metastasis has been established, the spatiotemporal process establishing a cancer metastasis-prone tissue microenvironment remains unknown. In this study, we aim to understand the immunological character of a metastasis-prone microenvironment in a murine 4T1 breast tumor model, by using the activation of nuclear factor-κb (NF-κB) in cancer cells as a sensor of inflammatory status and by monitoring its activity by bioluminescence imaging. By using a 4T1 breast cancer cell line stably expressing an NF-κB/Luc2 reporter gene (4T1 NF-κB cells), we observed significantly increased bioluminescence approximately 7 days after metastasis-prone orthotopic mammary fat-pad inoculation but not ectopic s.c. inoculation of 4T1 NF-κB cells. Such in vivo NF-κB activation within the fat-pad 4T1 tumor was diminished in immune-deficient SCID or nude mice, or T cell-depleted mice, suggesting the requirement of host T cell-mediated immune responses. Given the fat-pad 4T1 tumor expressed higher inflammatory mediators in a T cell-dependent mechanism compared to the s.c. tumor, our results imply the importance of the surrounding tissue microenvironment for inflaming tumors by collaborating with T cells to instigate metastatic spread of 4T1 breast cancer cells. PMID:25940224

  15. Towards an Automated MEMS-based Characterization of Benign and Cancerous Breast Tissue using Bioimpedance Measurements

    PubMed Central

    Pandya, Hardik J.; Kim, Hyun Tae; Roy, Rajarshi; Chen, Wenjin; Cong, Lei; Zhong, Hua; Foran, David J.; Desai, Jaydev P.

    2014-01-01

    Micro-Electro-Mechanical-Systems (MEMS) are desirable for use within medical diagnostics because of their capacity to manipulate and analyze biological materials at the microscale. Biosensors can be incorporated into portable lab-on-a-chip devices to quickly and reliably perform diagnostics procedure on laboratory and clinical samples. In this paper, electrical impedance-based measurements were used to distinguish between benign and cancerous breast tissues using microchips in a real-time and label-free manner. Two different microchips having inter-digited electrodes (10 µm width with 10 µm spacing and 10 µm width with 30 µm spacing) were used for measuring the impedance of breast tissues. The system employs Agilent E4980A precision impedance analyzer. The impedance magnitude and phase were collected over a frequency range of 100 Hz to 2 MHz. The benign group and cancer group showed clearly distinguishable impedance properties. At 200 kHz, the difference in impedance of benign and cancerous breast tissue was significantly higher (3110 Ω) in the case of microchips having 10 µm spacing compared to microchip having 30 µm spacing (568 Ω). PMID:25013305

  16. Quantification of Malignant Breast Cancer Cell MDA-MB-231 Transmigration Across Brain and Lung Microvascular Endothelium.

    PubMed

    Fan, Jie; Fu, Bingmei M

    2016-07-01

    Tumor cell extravasation through the endothelial barrier forming the microvessel wall is a crucial step during tumor metastasis. However, where, how and how fast tumor cells transmigrate through endothelial barriers remain unclear. Using an in vitro transwell model, we performed a transmigration assay of malignant breast tumor cells (MDA-MB-231) through brain and lung microvascular endothelial monolayers under control and pathological conditions. The locations and rates of tumor cell transmigration as well as the changes in the structural components (integrity) of endothelial monolayers were quantified by confocal microscopy. Endothelial monolayer permeability to albumin P (albumin) was also quantified under the same conditions. We found that about 98% of transmigration occurred at the joints of endothelial cells instead of cell bodies; tumor cell adhesion and transmigration degraded endothelial surface glycocalyx and disrupted endothelial junction proteins, consequently increased P (albumin); more tumor cells adhered to and transmigrated through the endothelial monolayer with higher P (albumin); P (albumin) and tumor transmigration were increased by vascular endothelial growth factor, a representative of cytokines, and lipopolysaccharides, a typical systemic inflammatory factor, but reduced by adenosine 3',5'-cyclic monophosphate. These results suggest that reinforcing endothelial structural integrity is an effective approach for inhibiting tumor extravasation. PMID:26603751

  17. Value of Virtual Touch Tissue Imaging Quantification for Evaluation of Ultrasound Breast Imaging-Reporting and Data System Category 4 Lesions.

    PubMed

    Li, Xiao-Long; Xu, Hui-Xiong; Bo, Xiao-Wan; Liu, Bo-Ji; Huang, Xian; Li, Dan-Dan; Guo, Le-Hang; Xu, Jun-Mei; Sun, Li-Ping; Fang, Lin; Xu, Xiao-Hong

    2016-09-01

    The purpose of the study was to evaluate the value of 2-D shear wave elastography (SWE) of virtual touch tissue imaging quantification (VTIQ) for ultrasound (US) Breast Imaging-Reporting and Data System (BI-RADS) category 4 lesions. One hundred sixteen lesions were subject to conventional US, conventional strain elastography (SE) of elasticity imaging (EI), acoustic radiation force impulse (ARFI)-induced SE of virtual touch tissue imaging (VTI) and VTIQ before biopsies. Of the 116 lesions, 69 (59.5%) were benign and 47 (40.5%) were malignant. Significant differences were found between benign and malignant lesions in EI score, VTI score and shear wave speed (SWS) on VTIQ (both p < 0.05). The cut-off values were EI score ≥4, VTI score ≥4 and SWS ≥3.49 m/s, respectively. The diagnostic performance of VTIQ in terms of area under receiver operating characteristic curve (AUROC) were the highest (i.e., AUROC = 0.907), in comparison with EI, VTI alone or a combination of both. The associated sensitivity, specificity and accuracy were 87.2%, 82.6% and 84.5%, respectively. The combination of VTI and VTIQ, however, was similar with US BI-RADS (p = 0.475) in sensitivity in that only two (4.3%) of 47 malignant lesions were misdiagnosed as benign that were BI-RADS category 4b on US. VTIQ is valuable to differentiate benign from malignant BI-RADS category 4 lesions, and the combination of VTI and VTIQ might be useful for patient selection before biopsy. PMID:27174418

  18. Loss of estrogen receptor beta expression in malignant human prostate cells in primary cultures and in prostate cancer tissues.

    PubMed

    Pasquali, D; Rossi, V; Esposito, D; Abbondanza, C; Puca, G A; Bellastella, A; Sinisi, A A

    2001-05-01

    The aim of this study was to investigate the expression of estrogen receptor (ER) beta and alpha genes in normal (N) and malignant (C) primary cultures of human prostate epithelial cells (PEC) and fibroblasts (PFC) and in the prostate tissue donors. Both ERbeta and ERalpha messenger ribonucleic acids were found by RT-PCR analysis in six NPECs and normal prostate tissues and in only one of six CPECs and in the respective cancer tissue donor. The other five CPECs and related cancer tissue donors and all normal and cancer PFCs expressed ERalpha messenger ribonucleic acid alone. Immunoblot analysis, using a polyclonal anti-ERbeta (C-terminal) antibody, demonstrated ERbeta protein in all NPEC lysates and in one of the six CPECS: ERalpha protein was expressed in both NPECs and CPECs when a polyclonal antibody directed against the ERalpha N-terminal domain was used. In contrast, ERalpha protein was not detected in two of the six CPEC lysates when ERalpha C-terminal monoclonal antibodies were used. Using a set of primers designed to amplify the region from exons 6-8, RT-PCR analysis demonstrated the absence of the expected transcript in these cells. The present study shows that the ERbeta gene is expressed together with ERalpha in normal prostates and NPECs, whereas it is barely detectable in prostate cancer and CPECS: Moreover, in some CPECs, the ERalpha gene may be transcribed in a changed protein, resulting from the expression of a deletion variant. Together, these data suggest that prostate malignancy is associated with a potential disorder of ER-mediated pathways. PMID:11344205

  19. Normal breast tissue implanted into athymic nude mice identifies biomarkers of the effects of human pregnancy levels of estrogen.

    PubMed

    Blance, Rognvald N; Sims, Andrew H; Anderson, Elizabeth; Howell, Anthony; Clarke, Robert B

    2009-03-01

    We have generated a novel model system for the study of estrogen intervention in normal breast tissue. Nulliparous human breast tissue was implanted into immunocompromised nude mice and treated with high-dose estrogen to simulate the effects of pregnancy. Treatment of mice with human mid-pregnancy levels of 17beta-estradiol for a period of 4 weeks was followed by 4 weeks of withdrawal to mimic involution. Gene expression in the xenograft tissue was then analyzed by real-time reverse transcription-PCR to identify differences between treated and control tissues. Ten genes previously identified as altered by pregnancy in rodent models were found to be differentially expressed in human breast tissue with a > or =1.8-fold up-regulation of CDC42, TGFbeta3, DCN, KRT14, LTF, and AREG and a > or =0.7-fold down-regulation of STAT1, CTGF, IGF1, and VAMP1. Immunohistochemical analysis of archival paraffin-embedded adult premenopausal human breast tissue specimens identified a significantly lower level of expression of STAT1 (P < 0.05, Mann-Whitney U test) in parous compared with age-matched nulliparous tissue (median of 24% compared with 42% epithelial cells positive). We conclude that many of the pregnancy-induced breast cancer-protective changes observed in rodent models also occur in human breast tissue following intervention using human pregnancy levels of estrogen and that STAT1 expression is a potential biomarker of parity-induced breast cancer protection in the human breast. PMID:19258541

  20. Optical pre-clinical diagnostics of the cervical tissues malignant changing

    NASA Astrophysics Data System (ADS)

    Yermolenko, Sergey; Voloshynskyi, Dmytro; Fedoruk, Olexander; Gruia, Ion; Zimnyakov, Dmitry

    2014-08-01

    This work is directed to the investigation of the scope of the technique of laser polarimetry of oncological changes of the human prostate and cervical tissues under the conditions of multiple scattering, which presents a more general and real experimental clinical situation. This study is combining polarimetry and spectropolarimetry techniques for identifying the changes of optical-geometrical structure in different kinds of biotissues with solid tumours. It is researched that a linear dichroism appears in biotissues (human esophagus, muscle tissue of rats, human prostate tissue, cervical smear) with cancer diseases, magnitude of which depends on the type of the tissue and on the time of cancer process development.

  1. A method to measure the hyperelastic parameters of ex vivo breast tissue samples

    NASA Astrophysics Data System (ADS)

    Samani, Abbas; Plewes, Donald

    2004-09-01

    Over the past decade, there has been increasing interest in modelling soft tissue deformation. This topic has several biomedical applications ranging from medical imaging to robotic assisted telesurgery. In these applications, tissue deformation can be very large due to low tissue stiffness and lack of physical constraints. As a result, deformation modelling of such organs often requires a treatment, which reflects nonlinear behaviour. While computational techniques such as nonlinear finite element methods are well developed, the required intrinsic nonlinear mechanical parameters of soft tissues that are critical to develop reliable tissue deformation models are not well known. To address this issue, we developed a system to measure the hyperelastic parameters of small ex vivo tissue samples. This measurement technique consists of indenting an unconfined small block of tissue using a computer controlled loading system while measuring the resulting indentation force. The nonlinear tissue force-displacement response is used to calculate the hyperelastic parameters via an appropriate inversion technique. This technique is based on a nonlinear least squares formulation that uses a nonlinear finite element model as the direct problem solver. The features of the system are demonstrated with two samples of breast tissue and typical hyperelastic results are presented.

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

    NASA Astrophysics Data System (ADS)

    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|

  3. Risk factors for mastectomy flap necrosis following immediate tissue expander breast reconstruction.

    PubMed

    Mlodinow, Alexei S; Fine, Neil A; Khavanin, Nima; Kim, John Y S

    2014-10-01

    Tissue expander placement is a mainstay of reconstructive surgery in the post-mastectomy patient. Necrosis of the native breast tissue is one of the most significant concerns in their post-operative care. The goal of this study is to elucidate factors that confer risk of this outcome. Chart review was conducted for a consecutive series of immediate tissue expander reconstructions by the two senior authors. Data was collected for several preoperative and intraoperative variables, as well as the outcome of mastectomy flap necrosis. Of the 1566 breasts that were examined, 135 (8.6%) experienced flap necrosis. The cohorts with and without flap necrosis were well matched. Those with the outcome of interest had significantly higher rates of switching to an autologous method of reconstruction (31.9% vs 6.2%, p < 0.001). Regression analysis revealed smoking status, increased age, tumescent mastectomy technique, and high (>66.67%) intraoperative tissue expander fill to confer increased risk of mastectomy flap necrosis. While smoking and older age are well-supported by the literature, tumescent technique and tissue expander fill are more novel points of discussion, which may serve as proxies for other issues. Awareness of these risk factors and their interplay will aid in clinical judgement and postoperative care of these patients. PMID:24495186

  4. Stem cells from adipose tissue and breast cancer: hype, risks and hope

    PubMed Central

    Bertolini, F; Petit, J-Y; Kolonin, M G

    2015-01-01

    Several recent papers have generated new hope about the use of white adipose tissue (WAT)-derived progenitor cells for soft tissue reconstruction in a variety of diseases including breast cancer (BC), a procedure that is increasingly used worldwide. We revised the available literature about WAT cells and BC. In the BC field, we believe that the hype for the exciting results in terms of WAT progenitor cell engraftment and tissue augmentation should be tempered when considering the recent and abundant preclinical studies, indicating that WAT progenitors may promote BC growth and metastasis. White adipose tissue progenitors can contribute to tumour vessels, pericytes and adipocytes, and were found to stimulate local and metastatic BC progression in several murine models. Moreover, there are clinical retrospective data showing a significant increase in the local recurrence frequency in patients with intraepithelial neoplasia who received a lipofilling procedure for breast reconstruction compared with controls. Retrospective and prospective clinical trials are warranted to investigate in depth the safety of this procedure in BC. Preclinical models should be used to find mechanisms able to inhibit the tumour-promoting activity of WAT progenitors while sparing their tissue reconstruction potential. PMID:25584493

  5. Protein profile study of clinical samples using laser induced fluorescence as the detection method: case of malignant and normal cervical tissues

    NASA Astrophysics Data System (ADS)

    Karemore, Gopal; Raja, Sujatha N.; Rai, Lavanya; Kartha, V. B.; Chidangil, Santhosh

    2009-02-01

    Protein profiles of tissue homogenates were recorded using HPLC separation and LIF detection method. The samples were collected from volunteers with clinically normal or cervical cancer conditions. It is shown that the protein profile can be classified as belonging to malignant or normal state by using hard and Fuzzy clustering methods. The study was performed to test the utility of the HPLC-LIF protein profiling method for classification of tissue samples as well as to establish a complementary method for histopathology for clinical diagnosis of the tissue as normal or malignant.

  6. Skin-sparing mastectomy and immediate tissue expander breast reconstruction in patients with macromastia using the Passot breast reduction pattern.

    PubMed

    Rinker, Brian; Thornton, Brian P

    2014-01-01

    Skin-sparing mastectomy (SSM) with immediate tissue expander reconstruction poses a challenge in the patient with macromastia or excessive ptosis. Skin reduction via the Wise pattern has been described but is associated with high rates of skin necrosis. The study group consisted of 43 women with grade 2 or 3 ptosis who underwent SSM and immediate reconstruction with tissue expanders, using the Passot (horizontal) skin reduction pattern. Age ranged from 31 to 67 years (mean, 51 years). The endpoints measured were time to final expansion, mastectomy skin flap necrosis, infectious complications, and total complications. Thirty reconstructions were bilateral and 13 were unilateral (73 breasts total). Follow-up ranged from 6 to 55 months (mean, 20). Common comorbid conditions included hypertension (n = 16), obesity (n = 22), and smoking (n = 9). The mean body mass index was 30.6 (range, 19.4-58.6). Twenty-one patients underwent chemotherapy; 12 received radiation. The mean initial fill was 196 mL (range, 0-420 mL), and the mean time to final expansion was 84 days (range, 28-225 days). Five patients did not complete the reconstruction, 2 because of cancer recurrence and 3 because of infection. There were 3 cases of mastectomy flap necrosis occurring after tissue expander placement (7%). There were 7 infectious complications (16%). The use of a horizontal breast reduction pattern at the time of expander placement produces consistently good esthetic outcomes and a low rate of skin necrosis, and it should be considered as an option in patients with macromastia or ptosis undergoing SSM and immediate reconstruction. PMID:24835873

  7. Estimation and imaging of breast lesions using a two-layer tissue structure by ultrasound-guided optical tomography

    NASA Astrophysics Data System (ADS)

    Xu, Yan; Zhu, Quing

    2015-06-01

    A new two-step estimation and imaging method is developed for a two-layer breast tissue structure consisting of a breast tissue layer and a chest wall underneath. First, a smaller probe with shorter distance source-detector pairs was used to collect the reflected light mainly from the breast tissue layer. Then, a larger probe with 9×14 source-detector pairs and a centrally located ultrasound transducer was used to collect reflected light from the two-layer tissue structure. The data collected from the smaller probe were used to estimate breast tissue optical properties. With more accurate estimation of the average breast tissue properties, the second layer properties can be assessed from data obtained from the larger probe. Using this approach, the unknown variables have been reduced from four to two and the estimated bulk tissue optical properties are more accurate and robust. In addition, a two-step reconstruction using a genetic algorithm and conjugate gradient method is implemented to simultaneously reconstruct the absorption and reduced scattering maps of targets inside a two-layer tissue structure. Simulations and phantom experiments have been performed to validate the new reconstruction method, and a clinical example is given to demonstrate the feasibility of this approach.

  8. Estimation and imaging of breast lesions using a two-layer tissue structure by ultrasound-guided optical tomography

    PubMed Central

    Xu, Yan; Zhu, Quing

    2015-01-01

    Abstract. A new two-step estimation and imaging method is developed for a two-layer breast tissue structure consisting of a breast tissue layer and a chest wall underneath. First, a smaller probe with shorter distance source-detector pairs was used to collect the reflected light mainly from the breast tissue layer. Then, a larger probe with 9×14 source-detector pairs and a centrally located ultrasound transducer was used to collect reflected light from the two-layer tissue structure. The data collected from the smaller probe were used to estimate breast tissue optical properties. With more accurate estimation of the average breast tissue properties, the second layer properties can be assessed from data obtained from the larger probe. Using this approach, the unknown variables have been reduced from four to two and the estimated bulk tissue optical properties are more accurate and robust. In addition, a two-step reconstruction using a genetic algorithm and conjugate gradient method is implemented to simultaneously reconstruct the absorption and reduced scattering maps of targets inside a two-layer tissue structure. Simulations and phantom experiments have been performed to validate the new reconstruction method, and a clinical example is given to demonstrate the feasibility of this approach. PMID:26046722

  9. Highly homologous hS100A15 and hS100A7 proteins are distinctly expressed in normal breast tissue and breast cancer

    PubMed Central

    Wolf, Ronald; Voscopoulos, Christopher; Winston, Jason; Dharamsi, Alif; Goldsmith, Paul; Gunsior, Michele; Vonderhaar, Barbara K.; Olson, Melanie; Watson, Peter H.; Yuspa, Stuart H.

    2009-01-01

    Human S100A7 (psoriasin) is considered a marker for specific stages of breast cancer. hS100A15 is almost identical to hS100A7 and difficult to discriminate. We developed specific probes to distinguish hS100A7 and hS100A15, and demonstrate their differential distribution in normal breast tissue. Further, hS100A7 and S100A15 transcripts are elevated in ER/PR negative breast cancers, but hS100A15 protein is detected in all cancer specimens while hS100A7 protein is sporadically expressed. The differential regulation, expression and distribution of hS100A7 and hS100A15 and their reported distinct functions are compelling reasons to discriminate among these proteins in normal breast and breast cancers. PMID:19136201

  10. Beyond the C18 frontier: Androgen and glucocorticoid metabolism in breast cancer tissues: The role of non-typical steroid hormones in breast cancer development and progression.