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Sample records for malignant breast tissue

  1. Optical spectroscopy of benign and malignant breast tissues

    NASA Astrophysics Data System (ADS)

    Yang, Yuanlong; Katz, Alvin; Celmer, Edward J.; Zurawska-Szczepaniak, Margaret; Alfano, Robert R.

    1996-04-01

    Fluorescence spectroscopy was applied to characterize normal, malignant and adipose breast tissues. Excitation, emission, and synchronized diffusive reflectance spectral scans were measured on over one hundred specimens for the purpose of developing an improved spectroscopic diagnostic technique. These techniques were able to successfully distinguish malignant tissue from adipose glandular fibrous and normal tissue. A sensitivity of 91% for fifty-six (56) malignant specimens with specificity of 91% for forty-six (46) benign tissue specimens has been achieved, using pathology as the golden standard.

  2. 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

  3. 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

  4. 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.

  5. 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.

  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. Estimate of tissue composition in malignant and benign breast lesions by time-domain optical mammography.

    PubMed

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

    2014-10-01

    The optical characterization of malignant and benign breast lesions is presented. Time-resolved transmittance measurements were performed in the 630-1060 nm range by means of a 7-wavelength optical mammograph, providing both imaging and spectroscopy information. A total of 62 lesions were analyzed, including 33 malignant and 29 benign lesions. The characterization of breast lesions was performed applying a perturbation model based on the high-order calculation of the pathlength of photons inside the lesion, which led to the assessment of oxy- and deoxy-hemoglobin, lipids, water and collagen concentrations. Significant variations between tumor and healthy tissue were observed in terms of both absorption properties and constituents concentration. In particular, benign lesions and tumors show a statistically significant discrimination in terms of absorption at several wavelengths and also in terms of oxy-hemoglobin and collagen content.

  8. Estimate of tissue composition in malignant and benign breast lesions by time-domain optical mammography

    PubMed Central

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

    2014-01-01

    The optical characterization of malignant and benign breast lesions is presented. Time-resolved transmittance measurements were performed in the 630-1060 nm range by means of a 7-wavelength optical mammograph, providing both imaging and spectroscopy information. A total of 62 lesions were analyzed, including 33 malignant and 29 benign lesions. The characterization of breast lesions was performed applying a perturbation model based on the high-order calculation of the pathlength of photons inside the lesion, which led to the assessment of oxy- and deoxy-hemoglobin, lipids, water and collagen concentrations. Significant variations between tumor and healthy tissue were observed in terms of both absorption properties and constituents concentration. In particular, benign lesions and tumors show a statistically significant discrimination in terms of absorption at several wavelengths and also in terms of oxy-hemoglobin and collagen content. PMID:25360382

  9. 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

  10. 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

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

    NASA Astrophysics Data System (ADS)

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

    2007-10-01

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

  12. 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.

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

    PubMed Central

    2013-01-01

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

  14. 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

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

    PubMed Central

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

    1990-01-01

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

  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. 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

  18. Malignant hemangiopericytoma of the breast.

    PubMed

    Kudawara, I; Ueda, T; Araki, N; Mori, S

    2001-01-01

    A55-year-old woman presented with 1-year history of mass in the right breast. Incisional biopsy showed the tumor to be malignant hemangiopericytoma from its histology. The tumor showed low--intermediate density and peripheral contrast enhancement on CT, and inhomogeneous mixed-signal intensity both on T1W and T2W images, and peripheral enhancement with Gd-DTPA on MRI with no invasion of the duct.

  19. 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

  20. Northwestern profiling of potential translation-regulatory proteins in human breast epithelial cells and malignant breast tissues: evidence for pathological activation of the IGF1R IRES.

    PubMed

    Blume, Scott W; Jackson, Nateka L; Frost, Andra R; Grizzle, William E; Shcherbakov, Oleg D; Choi, Hyoungsoo; Meng, Zheng

    2010-06-01

    Genes involved in the control of cell proliferation and survival (those genes most important to cancer pathogenesis) are often specifically regulated at the translational level, through RNA-protein interactions involving the 5'-untranslated region of the mRNA. IGF1R is a proto-oncogene strongly implicated in human breast cancer, promoting survival and proliferation of tumor cells, as well as metastasis and chemoresistance. Our lab has focused on the molecular mechanisms regulating IGF1R expression at the translational level. We previously discovered an internal ribosome entry site (IRES) within the 5'-untranslated region of the human IGF1R mRNA, and identified and functionally characterized two individual RNA-binding proteins, HuR and hnRNP C, which bind the IGF1R 5'-UTR and differentially regulate IRES activity. Here we have developed and implemented a high-resolution northwestern profiling strategy to characterize, as a group, the full spectrum of sequence-specific RNA-binding proteins potentially regulating IGF1R translational efficiency through interaction with the 5'-untranslated sequence. The putative IGF1R IRES trans-activating factors (ITAFs) are a heterogeneous group of RNA-binding proteins including hnRNPs originating in the nucleus as well as factors tightly associated with ribosomes in the cytoplasm. The IGF1R ITAFs can be categorized into three distinct groups: (a) high molecular weight external ITAFs, which likely modulate the overall conformation of the 5'-untranslated region of the IGF1R mRNA and thereby the accessibility of the core functional IRES; (b) low molecular weight external ITAFs, which may function as general chaperones to unwind the RNA, and (c) internal ITAFs which may directly facilitate or inhibit the fundamental process of ribosome recruitment to the IRES. We observe dramatic changes in the northwestern profile of non-malignant breast cells downregulating IGF1R expression in association with acinar differentiation in 3-D culture

  1. Arterial Microcalcifications in the Breast Mimicking Malignancy

    PubMed Central

    Janzen, Katrin; Janzen, Jan

    2012-01-01

    Microcalcifications in the breast are highly suggestive of malignancy; they can occur in many pathological conditions. A 36-years-old nondiabetic woman came to the gynaecologist with a suspect palpable mass in the upper outer quadrant of the right breast. Histopathological examination confirmed a calcification of a small artery (diameter: 0.45 mm). Arterial calcifications can mimic a malignant lesion in the breast. PMID:22606570

  2. Malignant solitary fibrous tumor of breast: a rare case report.

    PubMed

    Yang, Lian-He; Dai, Shun-Dong; Li, Qing-Chang; Xu, Hong-Tao; Jiang, Gui-Yang; Zhang, Yong; Wang, Liang; Fan, Chui-Feng; Wang, En-Hua

    2014-01-01

    Solitary fibrous tumor (SFT) is rare mesenchymal neoplasm that has been originally and most often documented in the pleura. Recently, the ubiquitous nature of the SFT has been recognized with reports of involvement of numerous sites all over the body such as: upper respiratory tract, somatic tissue, mediastinum, head, and neck. Less than 10 cases SFT of breast have been reported. Herein, we presented a 52-year-old Asian female with SFT of breast, this tumor showed predominant malignant features. To our knowledge, SFT of breast with such malignant evidence is extremely rare.

  3. 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.

  4. Optical biopsy of breast cancer tissue

    NASA Astrophysics Data System (ADS)

    AlSalhi, M. S.; Ben Amer, S.; Farhat, K.; Rabah, D.; Devanesan, S.; Atif, M.; Masilamani, V.; Al-Dakheel, Reem. K. S.

    2012-08-01

    In this paper, we report results of Fluorescence Emission Spectra (FES) and Stokes Shift Spectra (SSS) of 19 cancer tissue of invasive ductal carcinoma of different grades in comparison with normal breast tissues (obtained away from tumor regions). We were able to get distinct differences in the spectral features of normal and malignant tissues in terms of the ratios of concentrations of biomolecules like tryptophan, collagen and NADH. The sensitivity and specificity were in the range of 75%. What was all the more important was the parallelism in the spectral features of normal and malignant breast tissue pieces of above set of subjects. The objective of our research is to evolve one such protocol and the first step is the spectral characterization of in vitro optical analyses of excised tumor tissues.

  5. 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

  6. 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

  7. 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....

  8. 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

  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. Cholesterol granuloma of the breast mimicking malignancy

    PubMed Central

    Khan, Roobina; Narula, Varsha; Jain, Anshu; Maheshwari, Veena

    2013-01-01

    Cholesterol granuloma of the breast is an unusual non-neoplastic condition which frequently resembles malignancy clinically as well as radiologically. We herein report a case of a 28-year-old woman who presented with a lump in the upper outer quadrant of right breast. Physical examination and ultrasonography strongly suggested a carcinomatous lesion, but histopathological examination confirmed the diagnosis to be cholestrol granulomas. This article highlights the perplexing clinical presentation of cholesterol granulomas and affirms the role of histopathological examination in diagnosing these lesions correctly. PMID:23925685

  11. 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

  12. 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.

  13. 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

  14. Primary malignant lymphomas of the breast.

    PubMed

    Mambo, N C; Burke, J S; Butler, J J

    1977-05-01

    Fourteen cases of primary malignant lymphomas of the breast were found in the pathology files of the M. D. Anderson Hospital and Tumor Institute from 1944 to 1975. The lymphomas represented only 0.12% of 11,277 primary malignant breast tumors seen during the same period. There were no definite clinical features to distinguish the patients with lymphoma from those with breast carcinoma. All of the lymphomas had a diffuse pattern. Eight cases were classified as undifferentiated lymphoma, five as histiocytic, and one as poorly differentiated lymphocytic, convoluted cell type. Four patients had mastectomies and the remainder biopsies as their sole surgical procedure. Eight patients received post-surgical radiotherapy and all eventually had chemotherapy. The five-year survival rate for the 13 patients with follow-up was 49%. Patients with histiocytic lymphoma appeared to have a more favorable prognosis than those with the undifferentiated type. Six of the latter patients are dead with a median survival of seven months, comparable to the reported survival of patients with American Burkitt's lymphoma. The patient with the convoluted cell type has developed acute blastic leukemia and is currently under therapy.

  15. 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

  16. 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

  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. 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

  19. 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

  20. 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

  1. Nerve Fibers in Breast Cancer Tissues Indicate Aggressive Tumor Progression

    PubMed Central

    Huang, Di; Su, Shicheng; Cui, Xiuying; Shen, Ximing; Zeng, Yunjie; Wu, Wei; Chen, Jianing; Chen, Fei; He, Chonghua; Liu, Jiang; Huang, Wei; Liu, Qiang; Su, Fengxi; Song, Erwei; Ouyang, Nengtai

    2014-01-01

    Abstract Emerging evidence has indicated nerve fibers as a marker in the progression of various types of cancers, such as pancreatic cancer and prostate cancer. However, whether nerve fibers are associated with breast cancer progression remains unclear. In this study, we evaluated the presence of nerve fibers in 352 breast cancer specimens and 83 benign breast tissue specimens including 43 cases of cystic fibrosis and 40 cases of fibroadenoma from 2 independent breast tumor center using immunohistochemical staining for specific peripheral nerve fiber markers. In all, nerve fibers were present in 130 out of 352 breast cancer tissue specimens, while none were detected in normal breast tissue specimens. Among 352 cases, we defined 239 cases from Sun Yat-Sen Memorial Hospital, Guangzhou, China, as the training set, and 113 cases from the First Affiliated Hospital of Shantou University, Guangdong, China, as the validation set. The thickness of tumor-involving nerve fibers is significantly correlated with poor differentiation, lymph node metastasis, high clinical staging, and triple negative subtype in breast cancer. More importantly, Cox multifactor analysis indicates that the thickness of tumor-involving nerve fibers is a previously unappreciated independent prognostic factors associated with shorter disease-free survival of breast cancer patients. Our findings are further validated by online Oncomine database. In conclusion, our results show that nerve fiber involvement in breast cancer is associated with progression of the malignancy and warrant further studies in the future. PMID:25501061

  2. 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.

  3. Jack fruit lectin binding pattern in benign and malignant lesions of the breast.

    PubMed

    Remani, P; Augustine, J; Vijayan, K K; Ankathil, R; Vasudevan, D M; Nair, M K; Vijayakumar, T

    1989-01-01

    N-acetyl D-galactosamine specific lectin was isolated from Jack fruit (Artocarpus integrifolia) and conjugated to horse radish peroxidase type VI. The purified conjugate was used for the study of tissue binding properties on benign and malignant lesions of the breast using diaminobenzidine as substrate on dewaxed tissue sections. Forty mammary carcinomas, 10 cystic hyperplasias of the breast and 10 normal breast tissues were used for the study. Neoplastic cells showed increased affinity to the lectin. The lectin binding was focally strong in neoplastic cells compared to the normal as well as the hyperplastic tissues. The stroma of the cancer tissues showed an intense strong binding where elastosis was present. The use of the lectin as a histochemical reagent is discussed.

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

    PubMed

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

    2013-06-01

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

  5. Versican but not decorin accumulation is related to malignancy in mammographically detected high density and malignant-appearing microcalcifications in non-palpable breast carcinomas

    PubMed Central

    2011-01-01

    Background Mammographic density (MD) and malignant-appearing microcalcifications (MAMCs) represent the earliest mammographic findings of non-palpable breast carcinomas. Matrix proteoglycans versican and decorin are frequently over-expressed in various malignancies and are differently involved in the progression of cancer. In the present study, we have evaluated the expression of versican and decorin in non-palpable breast carcinomas and their association with high risk mammographic findings and tumor characteristics. Methods Three hundred and ten patients with non-palpable suspicious breast lesions, detected during screening mammography, were studied. Histological examination was carried out and the expression of decorin, versican, estrogen receptor α (ERα), progesterone receptor (PR) and c-erbB2 (HER-2/neu) was assessed by immunohistochemistry. Results Histological examination showed 83 out of 310 (26.8%) carcinomas of various subtypes. Immunohistochemistry was carried out in 62/83 carcinomas. Decorin was accumulated in breast tissues with MD and MAMCs independently of the presence of malignancy. In contrast, versican was significantly increased only in carcinomas with MAMCs (median ± SE: 42.0 ± 9.1) and MD (22.5 ± 10.1) as compared to normal breast tissue with MAMCs (14.0 ± 5.8), MD (11.0 ± 4.4) and normal breast tissue without mammographic findings (10.0 ± 2.0). Elevated levels of versican were correlated with higher tumor grade and invasiveness in carcinomas with MD and MAMCs, whereas increased amounts of decorin were associated with in situ carcinomas in MAMCs. Stromal deposition of both proteoglycans was related to higher expression of ERα and PR in tumor cells only in MAMCs. Conclusions The specific accumulation of versican in breast tissue with high MD and MAMCs only in the presence of malignant transformation and its association with the aggressiveness of the tumor suggests its possible use as molecular marker in non-palpable breast carcinomas

  6. 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

  7. Hypomethylation of the interleukin-10 gene in breast cancer tissues.

    PubMed

    Son, Keun Su; Kang, Han-Sung; Kim, Sun Jung; Jung, So-Youn; Min, Sun Young; Lee, See Youn; Kim, Seok Won; Kwon, Youngmee; Lee, Keun Seok; Shin, Kyung Hwan; Ro, Jungsil

    2010-12-01

    The purpose of the study was to evaluate the methylation status of the interleukin-10 (IL-10) gene in breast cancer tissues compared with normal and benign breast disease tissues. Between 2000 and 2001, we used paraffin-embedded specimens of 30 normal, 31 benign and 72 breast cancer tissues from the National Cancer Center, Korea. The methylation patterns of the IL-10 gene were evaluated using bisulfite DNA sequencing and the expression levels of IL-10 mRNA were evaluated using real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) and reverse transcriptase-polymerase chain reaction (RT-PCR). The methylation rates of the IL-10 gene were significantly lower in malignant tumors than in benign and normal tissues (normal; 63.3%, benign; 74.2%, cancer; 45.8%, p = 0.02). The methylation density rates of the IL-10 gene were also significantly lower in malignant tumors (normal; 59.68 ± 7.12%, benign; 48.89 ± 7.45%, cancer; 30.56 ± 4.18%, p = 0.001). Tissues with aberrant methylation of the IL-10 gene showed significantly lower rates of mRNA expression compared with unmethylated cases (12.5% vs. 68.0%, p = 0.012). The mRNA expression of tissues with unmethylated IL-10 was upregulated approximately ten thousand-fold compared to those with IL-10 methylation in the real-time RT-PCR experiment. IL-10 methylation demonstrated a significant association with lower expression of Ki-67 (9.36 ± 2.43 vs. 19.68 ± 3.42, p = 0.02). IL-10 methylation in cancer tissues is lower than that in normal and benign breast tissues, and DNA hypomethylation in the gene influences gene activation. Our data suggest that hypomethylation of the IL-10 gene can be involved in the process of breast carcinogenesis.

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

    PubMed

    Clevenger, C V; Plank, T L

    1997-01-01

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

  9. Zinc isotopic compositions of breast cancer tissue.

    PubMed

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

    2015-01-01

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

  10. 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.

  11. Ultrasound tomography of breast tissue

    NASA Astrophysics Data System (ADS)

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

    2003-05-01

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

  12. 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.

  13. 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.

  14. Needle optical coherence elastography for the measurement of microscale mechanical contrast deep within human breast tissues

    NASA Astrophysics Data System (ADS)

    Kennedy, Kelsey M.; McLaughlin, Robert A.; Kennedy, Brendan F.; Tien, Alan; Latham, Bruce; Saunders, Christobel M.; Sampson, David D.

    2013-12-01

    Optical coherence elastography (OCE) is an emerging imaging technique that probes microscale mechanical contrast in tissues with the potential to differentiate healthy and malignant tissues. However, conventional OCE techniques are limited to imaging the first 1 to 2 mm of tissue in depth. We demonstrate, for the first time, OCE measurements deep within human tissues using needle OCE, extending the potential of OCE as a surgical guidance tool. We use needle OCE to detect tissue interfaces based on mechanical contrast in both normal and malignant breast tissues in freshly excised human mastectomy samples, as validated against histopathology. Further, we demonstrate the feasibility of in situ measurements >4 cm from the tissue surface using ultrasound guidance of the OCE needle probe. With further refinement, our method may potentially aid in accurate detection of the boundary of the tumor to help ensure full removal of all malignant tissues, which is critical to the success of breast-conserving surgery.

  15. Synchronous luminescence spectroscopy of human breast tissues

    NASA Astrophysics Data System (ADS)

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

    1998-06-01

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

  16. 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.

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

    PubMed

    Kim, Youe Ree; Kim, Hun Soo; Kim, Hye-Won

    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

  18. 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

  19. 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

  20. 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

  1. Breast muscle tissue characteristics in growing broilers

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  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. 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.

  4. Quantification of acoustic radiation force impulse in differentiating between malignant and benign breast lesions.

    PubMed

    Li, Zhencai; Sun, Junzhong; Zhang, Jing; Hu, Dongmei; Wang, Qiong; Peng, Kun

    2014-02-01

    The aim of this study was to evaluate the use of gray-level quantification (GLQ) in virtual touch tissue imaging (VTI) in the differential diagnosis of breast lesions. GLQ values of 153 lesions (101 benign, 52 malignant) were analyzed with matrix laboratory software (MATLAB, The MathWorks, Natick, MA, USA), with gray levels ranging from 0 (pure black) to 255 (pure white). The diagnostic performance of GLQ was also evaluated using receiver operating characteristic curve analysis. The mean GLQ value for benign lesions (103.27 ± 39.44) differed significantly from that for malignant lesions (44.57 ± 13.61) (p < 0.001). At a cutoff value of 52.31, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 86.5%, 93.1%, 90.8%, 86.5% and 93.1%, respectively. In conclusion, we have proposed a method for quantification of gray levels in VTI for the differential diagnosis of breast lesions. Our results indicate that this method has the potential to aid in the classification of benign and malignant breast masses.

  5. 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

  6. 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

  7. p63 expression in benign and malignant breast lesions.

    PubMed

    Stefanou, D; Batistatou, A; Nonni, A; Arkoumani, E; Agnantis, N J

    2004-04-01

    The p63 gene encodes six protein isoforms. The transactivating isoforms have similar actions with p53, while the N-isoforms inhibit transcription activation by p53 and transactivating isoforms. p63 is expressed in stratified epithelia and in basal cells of the prostate and salivary glands. In mammary epithelium p63 has been shown to be expressed only in the myoepithelial layer. In the present study we investigated the immunohistochemical expression of p63, in benign and malignant breast lesions, and compared it with known myoepithelial cell markers. Our material consisted of 140 benign and 126 malignant breast lesions. We used the antibodies anti-p63, anti-alpha-smooth muscle actin, anti-S-100 protein and anti-cytokeratin 14. In all benign lesions, p63 immunoreactivity was noted in the myoepithelial cell layer surrounding the luminal epithelial cells. A less continuous peripheral rim of myoepithelial cells was also highlighted with p63-staining in all situ carcinomas. All invasive breast carcinomas were devoided of peripheral p63 staining. Interestingly, strong nuclear p63 immunoreactivity was noted in a small fraction (5-15%) of epithelial cells in all cases of papillomatosis, in 62.5% of in situ ductal papillary-type carcinomas and in 33.3% of invasive papillary carcinomas. Comparable staining was observed with S-100. The stromal cells were unreactive to p63. Our findings suggest that p63 is a sensitive and specific myoepithelial marker, and may be included in immunohistochemical panels aiming to identify myoepithelial cells in problematic breast lesions. Regarding papillary neoplasms, it is possible that tumor cells acquire and exhibit at least in part a myoepithelial differentiation program.

  8. 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

  9. Tabbed Tissue Expanders Improve Breast Symmetry Scores in Breast Reconstruction

    PubMed Central

    Khavanin, Nima; Gust, Madeleine J; Grant, David W; Nguyen, Khang T

    2014-01-01

    Background Achieving symmetry is a key goal in breast reconstruction. Anatomically shaped tabbed expanders are a new tool in the armamentarium of the breast reconstruction surgeon. Suture tabs allow for full control over the expander position and thus inframammary fold position, and, in theory, tabbed expanders mitigate many factors responsible for poor symmetry. The impact of a tabbed expander on breast symmetry, however, has not been formally reported. This study aims to evaluate breast symmetry following expander-implant reconstruction using tabbed and non-tabbed tissue expanders. Methods A chart review was performed of 188 consecutive expander-implant reconstructions that met the inclusion criteria of adequate follow-up data and postoperative photographs. Demographic, oncologic, postoperative complication, and photographic data was obtained for each patient. The photographic data was scored using a 4-point scale assessing breast symmetry by three blinded, independent reviewers. Results Of the 188 patients, 74 underwent reconstruction with tabbed expanders and 114 with non-tabbed expanders. The tabbed cohort had significantly higher symmetry scores than the non-tabbed cohort (2.82/4±0.86 vs. 2.55/4±0.92, P=0.034). Conclusions The use of tabbed tissue expanders improves breast symmetry in tissue expander-implant-based breast reconstruction. Fixation of the expander to the chest wall allows for more precise control over its location and counteracts the day-to-day translational forces that may influence the shape and location of the expander pocket, mitigating many factors responsible for breast asymmetry. PMID:24511496

  10. 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.

  11. Malignant breast tumors among atomic bomb survivors, Hiroshima and Nagasaki, 1950-74.

    PubMed

    Tokunaga, M; Norman, J E; Asano, M; Tokuoka, S; Ezaki, H; Nishimori, I; Tsuji, Y

    1979-06-01

    For 1950-74, 360 cases of malignant breast tumors were identified among the 63,000 females of the Radiation Effects Research Foundation's (Hiroshima and Nagasaki) Extended Life-Span Study sample of survivors of the 1945 atomic bombings of Hiroshima and Nagasaki; 288 of these females were residing in one of these two cities at the time of bombing (ATB). Two-thirds of all cases were classified as breast cancers on the basis of microscopic review of slides, and 108 cases received an estimated breast tissue dose of at least 10 rads. The number of cases of radiogenic breast cancer could be well estimated by a linear function of radiation dose for tissue doses below 200 rads. Excess risk estimates, based on this function, for women 10-19, 20-29, 30-39, and 50 years old or older ATB were 7.3, 4.2, 2.6, and 4.7 cases per million women per year per rad, respectively. Women irradiated in their forties showed no dose effect. Among all women who received at least 10 rads, those irradiated before age 20 years will have experienced the highest rates of breast cancer throughout their lifetimes. Separate excess risk estimates for Hiroshima and Nagasaki did not differ significantly, which indicates that for radiogenic breast cancer the effects of neutrons (emitted only in the Hiroshima explosion) and gamma radiation were about equal. Radiation did not reduce the latency period for the development of breast cancer, which was at least 10 years. The distribution of histologic types of cancers did not vary significantly with radiation dose. The data suggested that irradiation prior to menarche conferred a greater risk than irradiation after menarche.

  12. 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.

  13. 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.

  14. 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.

  15. [Surgical treatment of malignant soft tissue tumors].

    PubMed

    Amino, K; Kawaguchi, N; Matsumoto, S; Manabe, J; Furuya, K; Isobe, Y

    1987-05-01

    The ultimate survival of patients with soft tissue sarcoma is determined by a number of factors. Radical removal by adequate surgery is one of the most important factors together with early treatment and chemotherapy. We usually select curative wide resection, amputation, or resection after radiotherapy as forms of radical surgery for soft tissue sarcomas according to each clinical stage. The method of curative wide resection is based on biological barrier effects. In this report we discuss the operative results obtained in 148 cases of soft tissue sarcoma which we have treated over the past ten years, and also discuss the causes of recurrence after radical operation. Among 55 primary NoMo which were treated by the curative wide resection cases, the recurrence rate was 5.5%, the metastatic rate was 21.8%, and 5-year survival was 79.3%. These results were better than those for 30 recurrent and additional NoMo cases. Of cases involving the extremities, 81% were controlled by limb-saving operations. PMID:3592703

  16. Concordant HER2 status between metastatic breast cancer cells in CSF and primary breast cancer tissue.

    PubMed

    Park, In Hae; Kwon, Youngmee; Ro, Jae Y; Lee, Keun Seok; Ro, Jungsil

    2010-08-01

    It is not known whether the HER2 status of malignant CSF cells coincides with that of the original breast carcinoma cells. We investigated whether CSF cytology specimens were suitable to evaluate HER2 status by fluorescence in situ hybridization (FISH) in patient with leptomeningeal metastasis (LM). Both formalin-fixed paraffin-embedded (FFPE) breast cancer tissue and liquid based CSF cytology specimens were evaluated for HER2 status in 16 patients with LM. We evaluated HER2 gene amplification using FISH on destained CSF cytology slides containing a minimum of 20 malignant cells per slide, and compared these with the HER2 status by immunohistochemistry (IHC) or FISH in FFPE tissues. HER2 was considered positive when the HER2:CEP17 ratio was >or=2.0 or IHC 3+. Of 16 cases, four were HER2 positive and 12 were HER2 negative by FISH analysis in CSF cytology. All CSF-positive cases were HER2 positive by IHC in FFPE tissue. Of 12 HER2 FISH-negative cases in CSF cytology, 10 were HER2 negative (IHC 0 or 1+) and two were IHC 2+ in FFPE tissue. Two IHC 2+ cases had HER2:CEP17 ratios of 1.27 and 2.1, respectively, by FISH in FFPE tissue. As a result, the HER2 status concordance rate between metastatic breast cancer cells in CSF and FFPE primary tissue by IHC and FISH was very high. When CSF cytology specimens were appropriately prepared and had adequate cellularity without dry artifacts, the CSF cytology was suitable to evaluate HER2 status by FISH analysis in patients with LM.

  17. A subset of malignant phyllodes tumors express p63 and p40: a diagnostic pitfall in breast core needle biopsies.

    PubMed

    Cimino-Mathews, Ashley; Sharma, Rajni; Illei, Peter B; Vang, Russell; Argani, Pedram

    2014-12-01

    Breast phyllodes tumors are rare fibroepithelial neoplasms of variable grade, and one key differential of malignant phyllodes on core biopsy is sarcomatoid carcinoma. p63 is reported to be sensitive and specific for sarcomatoid carcinoma, with rare expression in phyllodes in limited series. The p63 deltaNp63 isoform, p40, is postulated to be more specific for squamous differentiation but has not previously been evaluated in breast phyllodes or sarcomatoid carcinoma. Tissue microarrays containing 34 unambiguous phyllodes tumors (10 benign, 10 borderline, 14 malignant), 13 sarcomatoid carcinomas, and 10 fibroadenomas were labeled by immunohistochemistry for p63, p40, CD34, and cytokeratins AE1/AE3, 34betaE12, and CK8/18. No borderline phyllodes tumor, benign phyllodes tumor, or fibroadenoma labeled with p63, p40, or cytokeratin. However, p63 labeled 57% malignant phyllodes tumors and 62% sarcomatoid carcinomas, and p40 labeled 29% malignant phyllodes (focal) and 46% sarcomatoid carcinomas. Among established markers, cytokeratins labeled 21% malignant phyllodes tumors (focal) and 100% sarcomatoid carcinomas. CD34 labeled 57% malignant phyllodes tumors and no sarcomatoid carcinomas. Focal p63, p40, and cytokeratin labeling can be seen in malignant phyllodes tumors but not in lower-grade fibroepithelial lesions, and immunoreactivity with these markers alone is not diagnostic of sarcomatoid carcinoma on core needle biopsy. In the differential diagnosis of malignant phyllodes, p40 is a more specific but less sensitive marker of sarcomatoid carcinoma than p63. These results are consistent with the sarcoma literature in which p63 labeling has been increasingly reported and suggest caution in classifying malignant spindle cell tumors of the breast on core biopsy.

  18. Primary malignant fibrous histiocytoma of the breast: report of one case

    PubMed Central

    Liu, Caigang; Zhao, Zuowei; Zhang, Qingfu; Wu, Yunfei; Jin, Feng

    2013-01-01

    Seven years ago, a 48-year-old female patient discovered a painless tumor in her right breast simply by chance. In the next year, the tumor increased significantly in size. At this point, the patient received a tumor resection, which was misdiagnosed as a benign mesenchymal tissue-originated tumor. Unfortunately, the tumor recurred just 10 days after resection. We subsequently resected the recurrent lesion and confirmed primary breast malignant fibrous histiocytoma. The tumor began to exhibit an unprecedented, massive, and uncontrolled growth, ulcerating soon after the operation. Treatment of the patient was limited by time. After the patient received a cycle of chemotherapy, she died of cachexia with the emergence of multiorgan metastasis 2 months after the operation. PMID:23589696

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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

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

    PubMed

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

    2004-10-01

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

  7. Lubricin in human breast tissue expander capsules.

    PubMed

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

    2012-10-01

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

  8. 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

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

    PubMed Central

    Jazayeri, Seyed Nematollah; Nateghi, Jamal

    2012-01-01

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

  10. Detection and genotyping of human papillomavirus in breast cancer tissues from Iraqi patients.

    PubMed

    Ali, S H M; Al-Alwan, N A S; Al-Alwany, S H M

    2014-06-18

    Studies have suggested a possible link between breast cancer pathogenesis and human papillomavirus (HPV) infection. This study in Iraq used in situ hybridization to detect the frequency and genotyping of HPV in tissue specimens from 129 patients diagnosed with malignant breast cancer, 24 with benign breast tumours and 20 healthy controls. In the breast cancer group, cocktail HPV genotypes were detected in 60 (46.5%) archived tissue blocks. Of these, genotypes 16 (55.5%), 18 (58.4%), 31 (65.0%) and 33 (26.6%) were detected. Mixed HPV genotypes 16 + 18, 16 + 18 + 31, 16 + 18 + 33, 18 + 33, 16 + 31 and 18 + 31 were found in 5.0%, 25.0%, 8.3%, 7.7%, 10.0% and 13.3% of cancer cases respectively. Only 3 benign breast tumour tissues (12.5%) and none of the healthy breast tissue specimens were HPV-DNA-positive. The detection of high-oncogenic HPV genotypes in patients with breast cancer supports the hypothesis of an etiologic role for the virus in breast cancer development.

  11. 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.

  12. 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

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

    PubMed

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

    2012-01-01

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

  14. 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.

  15. 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.

  16. Predicting the Risk of Secondary Lung Malignancies Associated with Whole Breast Radiation Therapy

    PubMed Central

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

    2014-01-01

    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 to 2.88, and RR 2.68, 95% CI 2.39 to 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 to 1.14) or the prone position (RR 1.01, 95% CI 0.88 to 1.15). Conclusions Compared to 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. PMID:22245205

  17. 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.

  18. Breast tumor malignancy modelling using evolutionary neural logic networks.

    PubMed

    Tsakonas, Athanasios; Dounias, Georgios; Panagi, Georgia; Panourgias, Evangelia

    2006-01-01

    The present work proposes a computer assisted methodology for the effective modelling of the diagnostic decision for breast tumor malignancy. The suggested approach is based on innovative hybrid computational intelligence algorithms properly applied in related cytological data contained in past medical records. The experimental data used in this study were gathered in the early 1990s in the University of Wisconsin, based in post diagnostic cytological observations performed by expert medical staff. Data were properly encoded in a computer database and accordingly, various alternative modelling techniques were applied on them, in an attempt to form diagnostic models. Previous methods included standard optimisation techniques, as well as artificial intelligence approaches, in a way that a variety of related publications exists in modern literature on the subject. In this report, a hybrid computational intelligence approach is suggested, which effectively combines modern mathematical logic principles, neural computation and genetic programming in an effective manner. The approach proves promising either in terms of diagnostic accuracy and generalization capabilities, or in terms of comprehensibility and practical importance for the related medical staff.

  19. Melatonin modulation of crosstalk among malignant epithelial, endothelial and adipose cells in breast cancer (Review).

    PubMed

    Cos, Samuel; Alvarez-García, Virginia; González, Alicia; Alonso-González, Carolina; Martínez-Campa, Carlos

    2014-08-01

    Melatonin, the main secretory product of the pineal gland, is an oncostatic agent that reduces the growth and development of various types of tumors, particularly mammary tumors whose growth is dependent on estrogens. Previous in vivo and in vitro studies point to the hypothesis that melatonin interplays with estrogen signaling pathways at three different levels: i) an indirect mechanism, by interfering with the hypothalamic-pituitary-reproductive axis in such way that the level of plasma estrogens synthesized by the gonadal glands are downregulated; ii) a direct mechanism of the pineal gland at the cell cancer level, disrupting the activation of estradiol receptors, therefore behaving as a selective estrogen receptor modulator; and iii) by regulating the enzymes involved in the biosynthesis of estrogens in other tissues, thus behaving as a selective estrogen enzyme modulator. The intratumoral metabolism and synthesis of estrogens, as a result of the interactions of various enzymes, is more important than blood uptake to maintain mammary gland estrogen levels in menopausal females. Additionally, estrogens are considered to play an important role in the pathogenesis and development of hormone-dependent breast carcinoma. Paracrine interactions among malignant epithelial cells and proximal adipose and endothelial cells, through cytokines and growth factors produced by breast tumor cells, modulate estrogen production at the mammary tumor level and, as a consequence, the genesis and development of mammary tumors. The aim of the present review is to summarize the recent findings describing the mechanisms by which melatonin is able to modulate the crosstalk among malignant epithelial, endothelial and adipose cells in breast cancer.

  20. Melatonin modulation of crosstalk among malignant epithelial, endothelial and adipose cells in breast cancer (Review).

    PubMed

    Cos, Samuel; Alvarez-García, Virginia; González, Alicia; Alonso-González, Carolina; Martínez-Campa, Carlos

    2014-08-01

    Melatonin, the main secretory product of the pineal gland, is an oncostatic agent that reduces the growth and development of various types of tumors, particularly mammary tumors whose growth is dependent on estrogens. Previous in vivo and in vitro studies point to the hypothesis that melatonin interplays with estrogen signaling pathways at three different levels: i) an indirect mechanism, by interfering with the hypothalamic-pituitary-reproductive axis in such way that the level of plasma estrogens synthesized by the gonadal glands are downregulated; ii) a direct mechanism of the pineal gland at the cell cancer level, disrupting the activation of estradiol receptors, therefore behaving as a selective estrogen receptor modulator; and iii) by regulating the enzymes involved in the biosynthesis of estrogens in other tissues, thus behaving as a selective estrogen enzyme modulator. The intratumoral metabolism and synthesis of estrogens, as a result of the interactions of various enzymes, is more important than blood uptake to maintain mammary gland estrogen levels in menopausal females. Additionally, estrogens are considered to play an important role in the pathogenesis and development of hormone-dependent breast carcinoma. Paracrine interactions among malignant epithelial cells and proximal adipose and endothelial cells, through cytokines and growth factors produced by breast tumor cells, modulate estrogen production at the mammary tumor level and, as a consequence, the genesis and development of mammary tumors. The aim of the present review is to summarize the recent findings describing the mechanisms by which melatonin is able to modulate the crosstalk among malignant epithelial, endothelial and adipose cells in breast cancer. PMID:25009641

  1. FDG-PET on the trail of an unsuspected primary malignancy in the breast.

    PubMed

    Dockery, Keith F; Puri, Savita; Qazi, Raman; Davis, Delphine

    2008-03-01

    Proper identification of the primary malignancy can radically alter clinical management for the patient's benefit. This is a report of an unsuspected primary breast cancer in a patient being worked up for presumptive lymphoma. Prior investigation of lymphedema in the left lower extremity found widespread lymphadenopathy on computed tomography imaging, leading to initial biopsy revealing adenocarcinoma of unknown primary. F-18 fluorodeoxyglucose PET/computed tomography altered management by localizing an F-18 fluorodeoxyglucose avid breast nodule, directing breast biopsy with specific immunohistochemical analysis for breast cancer lineage in metastatic adenocarcinoma. The patient responded well to breast cancer-targeted chemotherapy.

  2. 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.

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

    NASA Astrophysics Data System (ADS)

    Samani, Abbas; Zubovits, Judit; Plewes, Donald

    2007-03-01

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

  4. A Global View of Breast Tissue Banking.

    PubMed

    Wilson, Harriet; Botfield, Ben; Speirs, Valerie

    2015-01-01

    The importance of accessing high quality clinical samples for translational research is now firmly recognised. Traditionally these samples were collected and curated by individuals with an interest in a particular disease type. In recent years the idea of centralising and storing tissue collections in the form of tissue banks or biobanks has developed. As a result a number of biobanks have been established in many different countries. These can be either single centres or multi centre collaborations, often in the form of a federated network. This chapter outlines the development of breast tissue banking in a global context and discusses some of the challenges that lie ahead for the field, in particular how to meet the growing needs of researchers, how to make the best use of donated samples and how to increase the visibility of samples residing in biobanks to researchers.

  5. 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.

  6. High level PHGDH expression in breast is predominantly associated with keratin 5-positive cell lineage independently of malignancy.

    PubMed

    Gromova, Irina; Gromov, Pavel; Honma, Naoko; Kumar, Sudha; Rimm, David; Talman, Maj-Lis Møller; Wielenga, Vera Timmermans; Moreira, José M A

    2015-10-01

    We have previously reported the 2D PAGE-based proteomic profiling of a prospective cohort of 78 triple negative breast cancer (TNBC) patients, and the establishment of a cumulative TNBC protein database. Analysis of this database identified a number of proteins as being specifically overexpressed in TNBC samples. One such protein was D-3-phosphoglycerate dehydrogenase (Phgdh), a candidate oncogene. We analysed expression of Phgdh in normal and TNBC mammary tissue samples by 2D gel-based proteomics and immunohistochemistry (IHC), and show here that high-level expression of Phgdh in mammary epithelial cells is primarily associated with cell lineage, as we found that Phgdh expression was predominant in CK5-positive cells, normal as well as malignant, thus identifying an association of this protein with the basal phenotype. Quantitative IHC analysis of Phgdh expression in normal breast tissue showed high-level expression of Phgdh in normal CK5-positive mammary epithelial cells, indicating that expression of this protein was not associated with malignancy, but rather with cell lineage. However, proteomic profiling of Phgdh showed it to be expressed in two major protein forms, and that the ratio of expression between these variants was associated with malignancy. Overexpression of Phgdh in CK5-positive cell lineages, and differential protein isoform expression, was additionally found in other tissues and cancer types, suggesting that overexpression of Phgdh is generally associated with CK5 cells, and that oncogenic function may be determined by isoform expression.

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

    PubMed

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

    1975-01-01

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

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

    PubMed Central

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

    2003-01-01

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

  9. Hemoglobin enhances tissue factor expression on human malignant cells.

    PubMed

    Siddiqui, F A; Amirkhosravi, A; Amaya, M; Meyer, T; Biggerstaff, J; Desai, H; Francis, J L

    2001-04-01

    Tissue Factor (TF) is a transmembrane glycoprotein that complexes with factor VII/activated factor VII to initiate blood coagulation. TF may be expressed on the surface of various cells including monocytes and endothelial cells. Over-expression of TF in human tumor cell lines promotes metastasis. We recently showed that hemoglobin (Hb) forms a specific complex with TF purified from human malignant melanoma cells and enhances its procoagulant activity (PCA). To further study this interaction, we examined the effect of Hb on the expression of TF on human malignant (TF+) cells and KG1 myeloid leukemia (TF-) cells. Human melanoma A375 and J82 bladder carcinoma cells, which express TF at moderate and relatively high levels, respectively, were incubated with varying concentrations (0-1.5 mg/ml) of Hb. After washing, cells were analyzed for Hb binding and TF expression using flow cytometry and confocal microscopy. Hb bound to the cells in a concentration-dependent manner, and increased both TF expression and PCA. The human A375 malignant melanoma cells incubated with Hb (1 mg/ml) expressed up to six times more TF antigen than cells without Hb. This increase in TF expression and PCA of intact cells incubated with Hb was significantly inhibited by cycloheximide at a concentration of 10 microg/ml (P < 0.01). An increase in total cellular TF antigen content was demonstrated by specific immunoassay. In contrast, Hb (5 mg/ml) did not induce TF expression and PCA on KG1 cells as determined by flow cytometry and TF (FXAA) activity. We conclude that Hb specifically binds to TF-bearing malignant cells and increases their PCA. This effect seems to be at least partly due to de novo synthesis of TF and increased surface expression. However, the exact mechanism by which Hb binds and upregulates TF expression remains to be determined.

  10. Hemoglobin enhances tissue factor expression on human malignant cells.

    PubMed

    Siddiqui, F A; Amirkhosravi, A; Amaya, M; Meyer, T; Biggerstaff, J; Desai, H; Francis, J L

    2001-04-01

    Tissue Factor (TF) is a transmembrane glycoprotein that complexes with factor VII/activated factor VII to initiate blood coagulation. TF may be expressed on the surface of various cells including monocytes and endothelial cells. Over-expression of TF in human tumor cell lines promotes metastasis. We recently showed that hemoglobin (Hb) forms a specific complex with TF purified from human malignant melanoma cells and enhances its procoagulant activity (PCA). To further study this interaction, we examined the effect of Hb on the expression of TF on human malignant (TF+) cells and KG1 myeloid leukemia (TF-) cells. Human melanoma A375 and J82 bladder carcinoma cells, which express TF at moderate and relatively high levels, respectively, were incubated with varying concentrations (0-1.5 mg/ml) of Hb. After washing, cells were analyzed for Hb binding and TF expression using flow cytometry and confocal microscopy. Hb bound to the cells in a concentration-dependent manner, and increased both TF expression and PCA. The human A375 malignant melanoma cells incubated with Hb (1 mg/ml) expressed up to six times more TF antigen than cells without Hb. This increase in TF expression and PCA of intact cells incubated with Hb was significantly inhibited by cycloheximide at a concentration of 10 microg/ml (P < 0.01). An increase in total cellular TF antigen content was demonstrated by specific immunoassay. In contrast, Hb (5 mg/ml) did not induce TF expression and PCA on KG1 cells as determined by flow cytometry and TF (FXAA) activity. We conclude that Hb specifically binds to TF-bearing malignant cells and increases their PCA. This effect seems to be at least partly due to de novo synthesis of TF and increased surface expression. However, the exact mechanism by which Hb binds and upregulates TF expression remains to be determined. PMID:11414630

  11. 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

  12. 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

  13. Chemokine CXCL13 is overexpressed in the tumour tissue and in the peripheral blood of breast cancer patients

    PubMed Central

    Panse, J; Friedrichs, K; Marx, A; Hildebrandt, Y; Luetkens, T; Bartels, K; Horn, C; Stahl, T; Cao, Y; Milde-Langosch, K; Niendorf, A; Kröger, N; Wenzel, S; Leuwer, R; Bokemeyer, C; Hegewisch-Becker, S; Atanackovic, D

    2008-01-01

    The abilities of chemokines in orchestrating cellular migration are utilised by different (patho-)biological networks including malignancies. However, except for CXCR4/CXCL12, little is known about the relation between tumour-related chemokine expression and the development and progression of solid tumours like breast cancer. In this study, microarray analyses revealed the overexpression of chemokine CXCL13 in breast cancer specimens. This finding was confirmed by real-time polymerase chain reaction in a larger set of samples (n=34) and cell lines, and was validated on the protein level performing Western blot, ELISA, and immunohistochemistry. Levels of CXCR5, the receptor for CXCL13, were low in malignant and healthy breast tissues, and surface expression was not detected in vitro. However, we observed a strong (P=0.0004) correlation between the expressions of CXCL13 and CXCR5 in breast cancer tissues, indicating a biologically relevant role of CXCR5 in vivo. Finally, we detected significantly elevated serum concentrations of CXCL13 in patients with metastatic disease (n=54) as compared with controls (n=44) and disease-free patients (n=48). In conclusion, CXCL13 is overexpressed within breast cancer tissues, and increased serum levels of this cytokine can be found in breast cancer patients with metastatic disease pointing to a role of CXCL13 in the progression of breast cancer, suggesting that CXCL13 might serve as a useful therapeutic target and/or diagnostic marker in this malignancy. PMID:18781150

  14. 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.

  15. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2013-11-01

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

  17. Conclusiveness of fine needle aspiration in 2419 histologically confirmed benign and malignant breast lesions.

    PubMed

    Kooistra, B; Wauters, C; Wobbes, T; Strobbe, L

    2011-06-01

    We aimed to retrospectively assess (1) the conclusiveness of breast fine needle aspiration (FNA) in a histologically confirmed population and (2) the clinical and radiologic determinants of a conclusive diagnosis. Aspirates were diagnosed as inadequate, benign, atypical, suspicious or malignant. We defined a conclusive FNA diagnosis as 'benign' in histologically benign lesions and as 'malignant' in histologically malignant lesions. In 2419 breast lesions, the proportion of conclusive diagnoses was 46.1% (95% confidence interval, 42.0-50.2%) in histologically benign lesions (n = 571) and 81.6% (95% confidence interval, 79.8%-83.4%) in histologically malignant lesions (n = 1848). On multivariate analysis, factors associated with a conclusive preoperative diagnosis included tumour diameter of 2-2.9 cm (P < 0.001), malignant histology (P < 0.001) and the pathologist examining the aspirate (P = 0.02). Breast FNA has to be utilised selectively in the routine work-up of breast lesions. In suspicious lesions of large size, FNA may still be used to obtain a quick confirmation of malignancy.

  18. Lenvatinib and Capecitabine in Patients With Advanced Malignancies

    ClinicalTrials.gov

    2016-09-23

    Advanced Cancer; Malignant Neoplasm of Breast; Malignant Neoplasms of Bone and Articular Cartilage; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract

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

    PubMed

    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

  20. 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

  1. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2012-03-01

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

  3. MRI-Guided Diffuse Optical Spectroscopy of Malignant and Benign Breast Lesions1

    PubMed Central

    Ntziachristos, Vasilis; Yodh, A G; Schnall, Mitchell D; Chance, Britton

    2002-01-01

    Abstract We present the clinical implementation of a novel hybrid system that combines magnetic resonance imaging (MRI) and near-infrared (NIR) optical measurements for the noninvasive study of breast cancer in vivo. Fourteen patients were studied with a MR-NIR prototype imager and spectrometer. A diffuse optical tomographic scheme employed the MR images as a priori information to implement an image-guided NIR localized spectroscopic scheme. All patients who entered the study also underwent gadolinium-enhanced MRI and biopsy so that the optical findings were cross-validated with MR readings and histopathology. The technique quantified the oxy- and deoxyhemoglobin of five malignant and nine benign breast lesions in vivo. Breast cancers were found with decreased oxygen saturation and higher blood concentration than most benign lesions. The average hemoglobin concentration ([H]) of cancers was 0.130±0.100 mM, and the average hemoglobin saturation (Y) was 60±9% compared to [H]=0.018±0.005 mM and Y=69±6% of background tissue. Fibroadenomas exhibited high hemoglobin concentration [H]=0.060±0.010 mM and mild decrease in oxygen saturation Y=67±2%. Cysts and other normal lesions were easily differentiated based on intrinsic contrast information. This novel optical technology can be a significant add-on in MR examinations and can be used to characterize functional parameters of cancers with diagnostic and treatment prognosis potential. It is foreseen that the technique can play a major role in functional activation studies of brain and muscle as well. PMID:12082551

  4. Computer-aided, multi-modal, and compression diffuse optical studies of breast tissue

    NASA Astrophysics Data System (ADS)

    Busch, David Richard, Jr.

    Diffuse Optical Tomography and Spectroscopy permit measurement of important physiological parameters non-invasively through ˜10 cm of tissue. I have applied these techniques in measurements of human breast and breast cancer. My thesis integrates three loosely connected themes in this context: multi-modal breast cancer imaging, automated data analysis of breast cancer images, and microvascular hemodynamics of breast under compression. As per the first theme, I describe construction, testing, and the initial clinical usage of two generations of imaging systems for simultaneous diffuse optical and magnetic resonance imaging. The second project develops a statistical analysis of optical breast data from many spatial locations in a population of cancers to derive a novel optical signature of malignancy; I then apply this data-derived signature for localization of cancer in additional subjects. Finally, I construct and deploy diffuse optical instrumentation to measure blood content and blood flow during breast compression; besides optics, this research has implications for any method employing breast compression, e.g., mammography.

  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.

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

    PubMed Central

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

    2015-01-01

    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

  7. 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

  8. [Myoepithelial carcinoma in adenomyoepithelioma of the breast (malignant adenomyoepithelioma)--case report].

    PubMed

    Kinkor, Z

    2002-01-01

    There is described fifty-year-old woman with so called malignant adenomyoepithelioma of the breast. The conventional benign looking adenomyoepithelioma with biphasic tubular pattern continually fused to unequivocal invasive lesion which by immunophenotype turned out to be myoepithelial carcinoma. The 15 months follow up was uneventful. Extensive literature overview and terminology consideration is presented. The paper discusses biologic consequences of this rare breast lesion and its close resemblance to almost identical lesions in the salivary glands and skin adnexa.

  9. 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

  10. 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.

  11. Rosai-Dorfman disease presenting as a breast mass and enlarged axillary lymph node mimicking malignancy: a case report and review of the literature.

    PubMed

    Tenny, Steven O; McGinness, Marilee; Zhang, Da; Damjanov, Ivan; Fan, Fang

    2011-01-01

    Rosai-Dorfman disease (also called sinus histiocytosis with massive lymphadenopathy) involves lymph nodes or lymph nodes with extranodal sites. We present a unique case of a patient presenting with a breast mass and axillary lymphadenopathy, mimicking malignancy clinically and radiographically. Core needle biopsies of the breast and axillary lymph node showed histologic features concerning the lymphoma. However, excisional biopsy specimen demonstrated characteristic features of Rosai-Dorfman disease. The disease recurred locally 6 months later in the same breast, 1 month later in the contralateral breast, and 11 month later in the subcutaneous tissue of left flank. A review of the literature of Rosai-Dorfman disease involving the breast is also presented. PMID:21762247

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. Can texture of tissue surrounding microcalcifications in mammography be used for breast cancer diagnosis?

    NASA Astrophysics Data System (ADS)

    Karahaliou, A.; Boniatis, I.; Sakellaropoulos, P.; Skiadopoulos, S.; Panayiotakis, G.; Costaridou, L.

    2007-10-01

    This study investigates whether texture properties of the tissue surrounding microcalcifications (MCs) can contribute to breast cancer diagnosis. A case sample of 100 MC clusters (46 benign, 54 malignant) from 85 dense mammographic images included in the Digital Database for Screening Mammography, is analyzed. Regions of interest containing clusters are processed using wavelet-based enhancement and individual MCs are segmented by local thresholding. The segmented MCs are removed from original image data and the surrounding tissue area is subjected to texture analysis. The feasibility of four texture feature sets (first-order statistics, gray level co-occurrence matrices, gray level run length matrices and Laws' texture energy measures) in discriminating malignant from benign tissue was investigated using a k-nearest neighbor classifier. Laws' texture energy measures achieved the best classification accuracy 89% (sensitivity 90.74% and specificity 86.96%).

  17. Partial dependence of breast tumor malignancy on ultrasound image features derived from boosted trees

    NASA Astrophysics Data System (ADS)

    Yang, Wei; Zhang, Su; Li, Wenying; Chen, Yaqing; Lu, Hongtao; Chen, Wufan; Chen, Yazhu

    2010-04-01

    Various computerized features extracted from breast ultrasound images are useful in assessing the malignancy of breast tumors. However, the underlying relationship between the computerized features and tumor malignancy may not be linear in nature. We use the decision tree ensemble trained by the cost-sensitive boosting algorithm to approximate the target function for malignancy assessment and to reflect this relationship qualitatively. Partial dependence plots are employed to explore and visualize the effect of features on the output of the decision tree ensemble. In the experiments, 31 image features are extracted to quantify the sonographic characteristics of breast tumors. Patient age is used as an external feature because of its high clinical importance. The area under the receiver-operating characteristic curve of the tree ensembles can reach 0.95 with sensitivity of 0.95 (61/64) at the associated specificity 0.74 (77/104). The partial dependence plots of the four most important features are demonstrated to show the influence of the features on malignancy, and they are in accord with the empirical observations. The results can provide visual and qualitative references on the computerized image features for physicians, and can be useful for enhancing the interpretability of computer-aided diagnosis systems for breast ultrasound.

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

    PubMed

    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

    2016-01-12

    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.

  19. 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

  20. 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

  1. Model predictions for the wide-angle x-ray scatter signals of healthy and malignant breast duct biopsies.

    PubMed

    LeClair, Robert J; Ferreira, Andrew; McDonald, Nancy; Laamanen, Curtis; Tang, Robert Y

    2015-10-01

    Wide-angle x-ray scatter (WAXS) could potentially be used to diagnose ductal carcinoma in situ (DCIS) in breast biopsies. The regions of interest were assumed to consist of fibroglandular tissue and epithelial cells and the model assumed that biopsies with DCIS would have a higher concentration of the latter. The scattered number of photons from a 2-mm diameter column of tissue was simulated using a 110-kV beam and selectively added in terms of momentum transfer. For a 1-min exposure, specificities and sensitivities of unity were obtained for biopsies 2- to 20-mm thick. The impact of sample and tumor cell layer thicknesses was studied. For example, a biopsy erroneously estimated to be 8 mm would be correctly diagnosed if its actual thickness was between 7.3 and 8.7 mm. An 8-mm thick malignant biopsy can be correctly diagnosed provided the malignant cell layer thickness is [Formula: see text]. WAXS methods could become a diagnostic tool for DCIS within breast biopsies. PMID:26835493

  2. Use of Raman microspectroscopy to score the malignancy of breast cancer cells

    NASA Astrophysics Data System (ADS)

    Nieva, C.; Marro, M.; Sanz-Pamplona, R.; Santana-Codina, N.; Rao, S.; Petrov, D.; Sierra, A.

    2012-06-01

    It has been described that benign MCF10A breast cancer cell line suffers phenotypic changes toward malignancy when are cultured in sparse conditions. Using Raman spectroscopy with an InVia Raman microscope (Renishaw) with a backscattered configuration, we have studied the metabolic changes of confluent and sparse MCF10A cell cultures. We used Principal Component Analysis and Partial Least Squares Discriminant Analyses to assess the different profiling of the metabolic composition of breast cancer cells. The results indicated that Raman spectroscopy together with multivariate analysis is a useful technique to distinguish metabolic changes in malignant transformation. The identification of new metabolites, implementing the catalogue on the characterization of the different phenotypes associated to cell malignancy using Raman spectroscopy is under study.

  3. 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.

  4. 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.

  5. 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.

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

    PubMed

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

    2007-01-01

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

  7. The association of benign and malignant ovarian adenofibromas with breast cancer and thyroid disorders.

    PubMed

    Silva, Elvio G; Tornos, Carmen; Malpica, Anais; Deavers, Michael T; Tortolero-Luna, Guillermo; Gershenson, David M

    2002-01-01

    An unexpected association with breast cancer and thyroid disorders was found during a review of 91 cases of benign and malignant ovarian adenofibromas. Sixty-three tumors were benign, 11 had areas of borderline neoplasms, and 17 had a component of carcinoma. Such tumors were divided into glandular/cystic (61 cases) and papillary (30 cases) according to their gross and microscopic appearance. Among the 61 patients with glandular/cystic adenofibromas, 13 (21%) had breast cancer and 19 (31%) also had thyroid disorders. Among the 30 patients with papillary adenofibromas there were no cases of breast cancer and only 2 patients had thyroid disorders. The average age of the patients with ovarian adenofibroma and breast cancer or thyroid disorders was higher (66 years) than that of patients without breast cancer or thyroid disorders (55 years). More patients with breast cancer and thyroid disorders had bilateral adenofibromas than patients without breast cancer or thyroid disorders. We also reviewed the medical records of 100 patients with ovarian cancer without adenofibroma component, 100 patients with breast cancer, and 100 patients with ovarian and breast cancer. Six percent of patients with ovarian cancer had breast cancer and 16% of each one of these groups had thyroid disorders. This unexpected association found between glandular/cystic adenofibromas, breast cancer, and thyroid disorders might be explained by defects common to these organs. Disorders of some of these organs have been linked by common genetic changes and it is known that these organs are under the influence of similar hormones. Mutations of PTEN have been found in breast and thyroid cancer. The thyroid and ovaries are controlled by glycoprotein hormones of the pituitary gland, which have common alpha subunits.

  8. Is Serum Prostate-specific Antigen a Diagnostic Marker for Benign and Malignant Breast Tumors in Women?

    PubMed Central

    Razavi, Seyed Hasan Emami; Ghajarzadeh, Mahsa; Abdollahi, Alireza; Shoar, Saeed; Omranipour, Ramesh

    2015-01-01

    Background: Breast cancer is the most common cancer in women. Prostate-specific antigen (PSA) is a marker of prostate gland malignancy, which has been considered in cases with breast cancer in recent years. The goal of this study was to determine total and free PSA levels in cases with malignant and benign breast lesions. Methods: In this case–control study, ninety women with histological proved malignant breast masses and 90 with benign breast masses were enrolled. Total and free PSA levels along with Histological grade and conditions of vascular and perinural invasion, status of hormonal tumor receptors, immune-histo-chemistry markers recorded for all cases. Total and free PSA levels were assessed after treatment in cases with malignant masses. Results: Total and free PSA levels were significantly higher in cases with malignant masses. The best cut-off point for total PSA to differentiate benign and malignant masses was 0.31 with sensitivity and specificity of 100%, 100% (area under the curve [AUC] =1, P < 0.001) and the best cut-off point for free PSA to differentiate benign and malignant masses was 0.19 with sensitivity and specificity of 100% and 100% (AUC = 1, P < 0.001). After treatment, mean free PSA level was significantly lower than free PSA before treatment (0.23 ± 0.1 vs. 0.3 ± 0.08, P < 0.001). Conclusions: Serum PSA level could be applied for differentiating benign and malignant breast masses. PMID:25789147

  9. Large area mapping of excised breast tissue by fluorescence confocal strip scanning: a preliminary feasibility study

    NASA Astrophysics Data System (ADS)

    Larson, Bjorg A.; Abeytunge, Sanjee; Murray, Melissa; Rajadhyaksha, Milind

    2013-03-01

    Lumpectomy, in conjunction with radiation and chemotherapy drugs, together comprise breast-conserving treatment as an alternative to total mastectomy for patients with breast tumors. The tumor is removed in surgery and sent for pathology processing to assess the margins, a process that takes at minimum several hours, and generally days. If the margins are not clear of tumor, the patient must undergo a second surgery to remove residual tumor. This re-excision rate varies by institution, but can be as high as 60%. Currently, no intraoperative microscopic technique is used routinely to examine tumor margins in breast tissue. A new technique for rapidly scanning large areas of tissue has been developed, called confocal strip scanning, which provides high resolution and seamless mosaics over large areas of intact tissue, with nuclear and cellular resolution and optical sectioning of about 2 microns. Up to 3.5 x 3.5 cm2 of tissue is imaged in 13 minutes at current stage speeds. This technique is demonstrated in freshly excised breast tissue, using a mobile confocal microscope stationed in our pathology laboratory. Twenty-five lumpectomy and mastectomy cases were used as a testing ground for reflectance and fluorescence contrast modes, resolution requirements and tissue fixturing configurations. It was concluded that fluorescent imaging provides the needed contrast to distinguish ducts and lobules from surrounding stromal tissue. Therefore the system was configured with 488 nm illumination, with acridine orange fluorescent dye for nuclear contrast, with the aim of building an image library of malignant and benign breast pathologies.

  10. 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

  11. Simulation of effect of mechanical loading on dynamics of breast tissue optical properties

    NASA Astrophysics Data System (ADS)

    Dyachenko, Alexander; Gardner, John; Masyukov, Ivan V.; Rego, Alan; Zlatov, Vladimir

    2003-10-01

    Considering enhanced angiogenesis in malignant tissues we propose in a new functional imaging technique. If proven in clinical trial, the technique may be useful for differentiating malignant tumors with enhanced vascularity from normal tissues and benign lesions. The technique is based on observing the dynamics of light attenuation in the breast tissue in response to an external pressure stimulus. The attenuation is related to blood flow and blood oxygenation. In the proposed technique the measurements are made in the red spectral wavelength region where hemoglobin serves as a natural contrast agent. In order to understand and interpret the temporal dynamic of attenuation or signatures, a model of blood circulation in zones of tumor and normal tissues is developed. The blood volume, blood flow, and oxygen saturation level are evaluated using a lumped fluid flow model incorporating published hemodynamics data obtained from biopsy samples or in-situ chamber growth of human tumor. The hemodynamics properties are translated into normal tissues. The results suggest that the differences in the transient response may be used as a secondary diagnostic tool in breast imaging or as a monitoring tool in anti-angiogenesis drug therapy.

  12. Sodium iodide symporter (NIS) in extrathyroidal malignancies: focus on breast and urological cancer

    PubMed Central

    2014-01-01

    Background Expression and function of sodium iodide symporter (NIS) is requisite for efficient iodide transport in thyrocytes, and its presence in cancer cells allows the use of radioiodine as a diagnostic and therapeutic tool in thyroid neoplasia. Discovery of NIS expression in extrathyroidal tissues, including transformed cells, has opened a novel field of research regarding NIS-expressing extrathyroidal neoplasia. Indeed, expression of NIS may be used as a biomarker for diagnostic, prognostic, and therapeutic purposes. Moreover, stimulation of endogenous NIS expression may permit the radioiodine treatment of extrathyroidal lesions by concentrating this radioisotope. Results This review describes recent findings in NIS research in extrathyroidal malignancies, focusing on breast and urological cancer, emphasizing the most relevant developments that may have clinical impact. Conclusions Given the recent progress in the study of NIS regulation as molecular basis for new therapeutic approaches in extrathyroidal cancers, particular attention is given to studies regarding the relationship between NIS and clinical-pathological aspects of the tumors and the regulation of NIS expression in the experimental models. PMID:24884806

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

    PubMed

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

    2013-06-01

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

  14. Tissue modeling schemes in low energy breast brachytherapy.

    PubMed

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

    2011-11-21

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

  15. 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

  16. An Ectopic Breast Tissue Presenting with Fibroadenoma in Axilla

    PubMed Central

    Amaranathan, Anandhi; Balaguruswamy, Kanchana; Bhat, Ramachandra V.; Bora, Manash Kumar

    2013-01-01

    Introduction. The congenital anomalies of breast, especially the polymastia (supernumerary breast) and polythelia (supernumerary nipple), always do not fail to amuse the clinicians because of their varied presentations, associated renal anomalies, and pathologies arising from them. The axillary polymastia is a variant of ectopic breast tissue (EBT). Ectopic breast tissue can undergo the same physiological and pathological processes as the normally located breast. The incidence of fibroadenoma developing in ectopic breast is reported as a rare entity, the most common being the carcinoma. Case Presentation. A 31-year-old Dravidian female presented with a lump of 4 cm in the right axilla for the past year which gradually increased in size, giving discomfort. Our initial differential diagnosis was fibroadenoma, lipoma, and lymphadenopathy. Further investigation and histopathological report of excision biopsy confirmed it as a fibroadenoma on ectopic breast tissue in the axilla. Patient has no associated urological or cardiac anomaly. Conclusion. This case has been reported for its rarity and to reemphasise the importance of screening of EBT for any pathology during routine screening of breast. PMID:23607040

  17. Inflammation and increased aromatase expression occur in the breast tissue of obese women with breast cancer

    PubMed Central

    Morris, Patrick G.; Hudis, Clifford A.; Giri, Dilip; Morrow, Monica; Falcone, Domenick J.; Zhou, Xi Kathy; Du, Baoheng; Brogi, Edi; Crawford, Carolyn B.; Kopelovich, Levy; Subbaramaiah, Kotha; Dannenberg, Andrew J.

    2011-01-01

    Obesity is a risk factor for the development of hormone receptor-positive breast cancer in postmenopausal women and has been associated with an increased risk of recurrence and reduced survival. In humans, obesity causes subclinical inflammation in visceral and subcutaneous adipose tissue, characterized by necrotic adipocytes surrounded by macrophages forming crown-like structures (CLS). Recently, we found increased numbers of CLS, activation of the NF-κB transcription factor and elevated aromatase levels and activity in the mammary glands of obese mice. These preclinical findings raised the possibility that the obesity→inflammation axis is important for the development and progression of breast cancer. Here, our main objective was to determine if the findings in mouse models of obesity translated to women. Breast tissue was obtained from 30 women who underwent breast surgery. CLS of the breast (CLS-B) were found in nearly 50% (14 of 30) of patient samples. The severity of breast inflammation, defined as the CLS-B index, correlated with both body mass index (P<0.001) and adipocyte size (P=0.01). Increased NF-κB binding activity and elevated aromatase expression and activity were found in the inflamed breast tissue of overweight and obese women. Collectively, our results suggest that the obesity→inflammation→aromatase axis is present in the breast tissue of most overweight and obese women. The presence of CLS-B may be a biomarker of increased breast cancer risk or poor prognosis. PMID:21622727

  18. 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

  19. Hypoxia Drives Breast Tumor Malignancy through a TET-TNFα-p38-MAPK Signaling Axis.

    PubMed

    Wu, Min-Zu; Chen, Su-Feng; Nieh, Shin; Benner, Christopher; Ger, Luo-Ping; Jan, Chia-Ing; Ma, Li; Chen, Chien-Hung; Hishida, Tomoaki; Chang, Hong-Tai; Lin, Yaoh-Shiang; Montserrat, Nuria; Gascon, Pedro; Sancho-Martinez, Ignacio; Izpisua Belmonte, Juan Carlos

    2015-09-15

    Hypoxia is a hallmark of solid tumors that drives malignant progression by altering epigenetic controls. In breast tumors, aberrant DNA methylation is a prevalent epigenetic feature associated with increased risk of metastasis and poor prognosis. However, the mechanism by which hypoxia alters DNA methylation or other epigenetic controls that promote breast malignancy remains poorly understood. We discovered that hypoxia deregulates TET1 and TET3, the enzymes that catalyze conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), thereby leading to breast tumor-initiating cell (BTIC) properties. TET1/3 and 5hmC levels were closely associated with tumor hypoxia, tumor malignancy, and poor prognosis in breast cancer patients. Mechanistic investigations showed that hypoxia leads to genome-wide changes in DNA hydroxymethylation associated with upregulation of TNFα expression and activation of its downstream p38-MAPK effector pathway. Coordinate functions of TET1 and TET3 were also required to activate TNFα-p38-MAPK signaling as a response to hypoxia. Our results reveal how signal transduction through the TET-TNFα-p38-MAPK signaling axis is required for the acquisition of BTIC characteristics and tumorigenicity in vitro and in vivo, with potential implications for how to eradicate BTIC as a therapeutic strategy. PMID:26294212

  20. 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

  1. 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

  2. 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.

  3. Optical spectral fingerprints of tissues from patients with different breast cancer histologies using a novel fluorescence spectroscopic device.

    PubMed

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

    2013-10-01

    The fluorescence of paired human breast malignant and normal tissue samples was investigated using a novel fluorescence spectroscopic (S3-LED) ratiometer unit with no moving parts. This device can measure the emission spectra of key native organic biomolecules such as tryptophan, tyrosine, collagen and elastin within tissues by using LED (light emitting diode) excitation sources coupled to an optical fiber. With this device, the spectral profiles of 11 paired breast cancerous and normal samples from 11 patients with breast carcinoma were obtained. In each of the 11 cases, marked increases in the tryptophan levels were found in the breast carcinoma samples when compared to the normal breast tissues. In the breast cancer samples, there were also consistently higher ratios of the 340 to 440 nm and the 340 to 460 nm intensity peaks after 280 nm excitation, likely representing an increased tryptophan to NADH ratio in the breast cancer samples. This difference was seen in the spectral profiles of the breast cancer patients regardless of whether they were HER2 positive or negative or hormone receptor positive or negative, and was found regardless of menopausal status, histology, stage, or tumor grade.

  4. ATM suppresses SATB1-induced malignant progression in breast epithelial cells.

    PubMed

    Ordinario, Ellen; Han, Hye-Jung; Furuta, Saori; Heiser, Laura M; Jakkula, Lakshmi R; Rodier, Francis; Spellman, Paul T; Campisi, Judith; Gray, Joe W; Bissell, Mina J; Kohwi, Yoshinori; Kohwi-Shigematsu, Terumi

    2012-01-01

    SATB1 drives metastasis when expressed in breast tumor cells by radically reprogramming gene expression. Here, we show that SATB1 also has an oncogenic activity to transform certain non-malignant breast epithelial cell lines. We studied the non-malignant MCF10A cell line, which is used widely in the literature. We obtained aliquots from two different sources (here we refer to them as MCF10A-1 and MCF10A-2), but found them to be surprisingly dissimilar in their responses to oncogenic activity of SATB1. Ectopic expression of SATB1 in MCF10A-1 induced tumor-like morphology in three-dimensional cultures, led to tumor formation in immunocompromised mice, and when injected into tail veins, led to lung metastasis. The number of metastases correlated positively with the level of SATB1 expression. In contrast, SATB1 expression in MCF10A-2 did not lead to any of these outcomes. Yet DNA copy-number analysis revealed that MCF10A-1 is indistinguishable genetically from MCF10A-2. However, gene expression profiling analysis revealed that these cell lines have significantly divergent signatures for the expression of genes involved in oncogenesis, including cell cycle regulation and signal transduction. Above all, the early DNA damage-response kinase, ATM, was greatly reduced in MCF10A-1 cells compared to MCF10A-2 cells. We found the reason for reduction to be phenotypic drift due to long-term cultivation of MCF10A. ATM knockdown in MCF10A-2 and two other non-malignant breast epithelial cell lines, 184A1 and 184B4, enabled SATB1 to induce malignant phenotypes similar to that observed for MCF10A-1. These data indicate a novel role for ATM as a suppressor of SATB1-induced malignancy in breast epithelial cells, but also raise a cautionary note that phenotypic drift could lead to dramatically different functional outcomes.

  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. Malignancy Rate, Number Needed to Treat, and Positive Predictive Value for Breast MRI.

    PubMed

    Kennedy, John S; Robbins, Patrick A

    2016-09-01

    Breast MRI is being used more frequently for advanced screening for breast cancer. Patients may be at increased risk, or are symptomatic, with nonsuspicious mammograms. There is little data regarding the likelihood of a recommendation for biopsy, or for detecting a malignancy, in this population. We intended to determine the malignancy rate, number needed to treat, and positive predictive value for patients receiving adjunctive MRI at our institution. A retrospective review of all breast MRIs from 2008 to 2010 was done. Patients with any prior diagnosis of breast cancer, or BRCA+ were excluded. There were 324 patients. Most common reasons for ordering the breast MRI included: abnormal test result 130 (44%), palpable mass 74 (23%), family history 58 (18%), breast pain 47 (15%), and nipple discharge 45 (14%). Breast Imaging-Reporting and Data System score (BIRADS) was 1 or 2 in 36 per cent, 4 or 5 in 18 per cent, 3 in 26 per cent, 0 in 10 per cent, and not given in 9 per cent. Biopsy was recommended in 77 (24%), with biopsy actually performed in 57 (18%). Of the eight cancers identified, four (1.2%) were ductal carcinoma in situ (DCIS) and four (1.2%) were invasive cancer, yielding a true-positive rate of 2.5 per cent. Number needed to treat was 40. Positive predictive value was 14 per cent with a false-positive rate of 86 per cent. In this group of generally higher risk women, typically prescreened with mammography, 1.2 per cent had an invasive cancer, and another 1.2 per cent had DCIS. Those who undergo biopsy are 6.1 times more likely to have benign pathology. The efficacy of adjunctive breast MRI could be improved through refinements in indication, test interpretation, or alternative screening strategies.

  7. 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

  8. 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.

  9. Hemostatic alterations are unrelated to the stage of tumor in untreated malignant melanoma and breast carcinoma.

    PubMed

    Mannucci, P M; Vaglini, M; Maniezzo, M; Magni, E; Mari, D; Cascinelli, N

    1985-06-01

    A study of hemostatic variables was carried out in 80 untreated patients with breast adenocarcinoma or malignant melanoma, chosen as examples of tumors that can be accurately staged for localization or spread. The most marked abnormalities were high levels of clotting factors V and VIII, plasminogen, von Willebrand factor and fibrogen-fibrin degradation products. These abnormalities occurred in both types of tumors, albeit slightly more markedly in melanomas, and were also present in localized tumors. Our data indicate that in tumors, abnormalities of the hemostatic system are an early phenomenon unrelated to the presence of widespread malignancy.

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

    PubMed Central

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

    2010-01-01

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

  11. Inhibitors of Rho kinase (ROCK) signaling revert the malignant phenotype of breast cancer cells in 3D context.

    PubMed

    Matsubara, Masahiro; Bissell, Mina J

    2016-05-31

    Loss of polarity and quiescence along with increased cellular invasiveness are associated with breast tumor progression. ROCK plays a central role in actin-cytoskeletal rearrangement. We used physiologically relevant 3D cultures of nonmalignant and cancer cells in gels made of laminin-rich extracellular matrix, to investigate ROCK function. Whereas expression levels of ROCK1 and ROCK2 were elevated in cancer cells compared to nonmalignant cells, this was not observed in 2D cultures. Malignant cells showed increased phosphorylation of MLC, corresponding to disorganized F-actin. Inhibition of ROCK signaling restored polarity, decreased disorganization of F-actin, and led to reduction of proliferation. Inhibition of ROCK also decreased EGFR and Integrinβ1 levels, and consequently suppressed activation of Akt, MAPK and FAK as well as GLUT3 and LDHA levels. Again, ROCK inhibition did not inhibit these molecules in 2D. A triple negative breast cancer cell line, which lacks E-cadherin, had high levels of ROCK but was less sensitive to ROCK inhibitors. Exogenous overexpression of E-cadherin, however, rendered these cells strikingly sensitive to ROCK inhibition. Our results add to the growing literature that demonstrate the importance of context and tissue architecture in determining not only regulation of normal and malignant phenotypes but also drug response.

  12. Wavelet-based feature extraction applied to small-angle x-ray scattering patterns from breast tissue: a tool for differentiating between tissue types.

    PubMed

    Falzon, G; Pearson, S; Murison, R; Hall, C; Siu, K; Evans, A; Rogers, K; Lewis, R

    2006-05-21

    This paper reports on the application of wavelet decomposition to small-angle x-ray scattering (SAXS) patterns from human breast tissue produced by a synchrotron source. The pixel intensities of SAXS patterns of normal, benign and malignant tissue types were transformed into wavelet coefficients. Statistical analysis found significant differences between the wavelet coefficients describing the patterns produced by different tissue types. These differences were then correlated with position in the image and have been linked to the supra-molecular structural changes that occur in breast tissue in the presence of disease. Specifically, results indicate that there are significant differences between healthy and diseased tissues in the wavelet coefficients that describe the peaks produced by the axial d-spacing of collagen. These differences suggest that a useful classification tool could be based upon the spectral information within the axial peaks.

  13. A novel biomarker C6orf106 promotes the malignant progression of breast cancer.

    PubMed

    Jiang, Guiyang; Zhang, Xiupeng; Zhang, Yong; Wang, Liang; Fan, Chuifeng; Xu, Hongtao; Miao, Yuan; Wang, Enhua

    2015-09-01

    C6orf106 (chromosome 6 open reading frame 106) is a recently discovered protein encoded by the 6th chromosome. Though many proteins encoded by chromosome 6 are reportedly related to cancer, schizophrenia, autoimmunity and many other diseases, the function of C6orf106 was not well demonstrated so far. As measured by immunohistochemical staining, C6orf106 was positive in normal breast duct myoepithelial cells (92.31 %, 72/78), but negative in normal breast duct glandular epithelial cells (3.85 %, 3/78). In breast ductal carcinoma in situ, C6orf106 showed weakly or moderately positive (77.97 %, 46/59), but it was significantly strongly positive in invasive ductal carcinoma (79.57 %, 148/186). The expression intensity of C6orf106 seemed increased significantly along with the malignancy of breast cancer (p < 0.001). Additionally, C6orf106 expression was significantly correlated with TNM stage (p = 0.001 and p = 0.004) and lymph node metastasis (p = 0.018 and p = 0.025) of the overall and the triple-negative breast cancer, respectively. Consistently, we found that the interference of C6orf106 was able to inhibit cell proliferation and invasion of two triple-negative breast cancer cell lines, MDA-MB-231 and BT-549, accompanied by the decrease of cyclin A2, cyclin B1, c-myc, and N-cadherin and the increase of E-cadherin. Collectively, these results indicate that C6orf106 may promote tumor progression in the invasive breast cancer, particularly in triple-negative breast cancer, and C6orf106 might serve as a novel therapeutic target of breast cancer, especially for triple-negative breast cancer.

  14. 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

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

    PubMed

    Danforth, David N

    2016-01-01

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

  16. Intercostal nerves block for mastectomy in two patients with advanced breast malignancy.

    PubMed

    Kolawole, Israel K; Adesina, Michael D; Olaoye, Iyiade O

    2006-03-01

    Regional anesthesia is recognized as an alternative to general anesthesia for modern breast cancer surgery. Various techniques of block have been described. Each has its unique problems. Regional anesthesia was chosen for simple mastectomy in two patients with advanced breast malignancy, due to compromised pulmonary status resulting from widespread malignant infiltration of both lungs. We used intercostal nerves block. The block was supplemented with an infraclavicular infiltration to interrupt the branches of the superficial cervical plexus that provide sensation to the upper chest wall and subcutaneous infiltration in the midline to block the nerve supply from the contralateral side. Anesthesia was generally effective and the operations were uneventful. Both patients and surgeons expressed satisfaction. We conclude that where patients have significant comorbidities that make general anesthesia undesirable, the use of intercostal nerves block remains a safe and reliable anesthetic option that allows the patient access to surgery for simple mastectomy.

  17. Breast malignant phyllodes tumor with rare pelvic metastases and long-term overall survival

    PubMed Central

    Shan, Jinlan; Zhang, Shizhen; Wang, Zhen; Fu, Yanbiao; Li, Ling; Wang, Xiaochen

    2016-01-01

    Abstract Background: Malignant phyllodes tumor (PT) is a rare fibro epithelial neoplasm of the breast, which is poor prognosis due to high risk of recurrence and distant metastasis. Methods: We report a case of malignant PT. It had recurred locally five times, and the sixth relapse was occurred 54 months after first diagnosis, presenting a huge pelvic mass (14 cm × 11 cm) by CT scan. Histopathological examination has demonstrated a metastatic phyllodes tumor. After postoperative chemotherapy treatment, a longer survival has been achieved, which is more than 72 months. Results: Our case report describes a breast PT with several local recurrences and a rare metastasis (pelvic cavity), but long-term overall survival was achieved after surgery and chemotherapy. Conclusion: We conclude that trustworthy prognosticators that identify patients with excessive potential of aggressive clinical course should be explored. Moreover, proper treatment could prolong overall survival of metastatic PT patients. PMID:27661051

  18. 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

  19. 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.

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

    PubMed

    Chen, D B; Yang, H J

    2014-11-11

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

  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. Assessment of Breast Specimens With or Without Calcifications in Diagnosing Malignant and Atypia for Mammographic Breast Microcalcifications Without Mass

    PubMed Central

    Cheung, Yun-Chung; Juan, Yu-Hsiang; Ueng, Shir-Hwa; Lo, Yung-Feng; Huang, Pei-Chin; Lin, Yu-Ching; Chen, Shin-Cheh

    2015-01-01

    Abstract Presence of microcalcifications within the specimens frequently signifies a successful attempt of stereotactic vacuum-assisted breast biopsy (VABB) in obtaining a pathologic diagnosis of the breast microcalcifications. In this study, the authors aimed to assess and compare the accuracy and consistency of calcified or noncalcified specimens obtained from same sites of sampling on isolated microcalcifications without mass in diagnosing high-risk and malignant lesions. To the best of our knowledge, an individual case-based prospective comparison has not been reported. With the approval from institutional review board of our hospital (Chang Gung Memorial Hospital), the authors retrospectively reviewed all clinical cases of stereotactic VABBs on isolated breast microcalcifications without mass from our database. The authors included those having either surgery performed or had clinical follow-up of at least 3 years for analysis. All the obtained specimens with or without calcification were identified using specimen radiographs and separately submitted for pathologic evaluation. The concordance of diagnosis was assessed for both atypia and malignant lesions. A total of 390 stereotactic VABB procedures (1206 calcified and 1456 noncalcified specimens) were collected and reviewed. The consistent rates between calcified and noncalcified specimens were low for atypia and malignant microcalcifications (44.44% in flat epithelial atypia, 46.51% in atypical ductal hyperplasia, 55.73% in ductal carcinoma in situ, and 71.42% in invasive ductal carcinoma). The discordance in VABB diagnoses indicated that 41.33% of malignant lesions would be misdiagnosed by noncalcified specimens. Furthermore, calcified specimens showed higher diagnostic accuracy of breast cancer as compared with the noncalcified specimens (91.54 % versus 69.49%, respectively). The evaluation of both noncalcified specimens and calcified specimens did not show improvement of diagnostic accuracy as compared

  3. 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.

  4. Development of breast cancer tissue phantoms for terahertz imaging

    NASA Astrophysics Data System (ADS)

    Walter, Alec; Bowman, Tyler; El-Shenawee, Magda

    2016-03-01

    The goal of this work was to develop phantoms that match the refractive indices and absorption coefficients between 0.15 and 2.0 THz of the freshly excised tissues commonly found in breast tumors. Since a breast cancer tumor can contain fibrous and fatty tissues alongside the cancerous tissues, a phantom had to be developed for each. In order to match the desired properties of the tissues, oil in water emulsions were solidified using the proven phantom component TX151. The properties of each potential phantom were verified through THz time-domain spectroscopy on a TPS Spectra 3000. Using this method, phantoms for fibrous and cancerous tissue were successfully developed while a commercially available material was found which matched the optical properties of fatty tissue.

  5. Systemic alteration of cell-surface and secreted glycoprotein expression in malignant breast cancer cell lines.

    PubMed

    Timpe, Leslie C; Yen, Roger; Haste, Nicole V; Litsakos-Cheung, Christina; Yen, Ten-Yang; Macher, Bruce A

    2013-11-01

    Breast cancer cell lines express fewer transmembrane and secreted glycoproteins than nonmalignant ones. The objective of these experiments was to characterize the changes in the expression of several hundred glycoproteins quantitatively. Secreted and cell-surface glycoproteins were isolated using a glycoprotein capture protocol and then identified by tandem mass spectrometry. Glycoproteins expressed by a group of cell lines originating from malignant tumors of the breast were compared with those expressed by a nonmalignant set. The average number of spectral counts (proportional to relative protein abundance) and the total number of glycopeptides in the malignant samples were reduced to about two-thirds of the level in the nonmalignant samples. Most glycoproteins were expressed at a different level in the malignant samples, with nearly as many increasing as decreasing. The glycoproteins with reduced expression accounted for a larger change in spectral counts, and hence for the net loss of spectral counts in the malignant lines. Similar results were found when the glycoproteins were studied via identified glycosylation sites only, or through identified sites together with non-glycopeptides. The overall reduction is largely due to the loss of integrins, laminins and other proteins that form or interact with the basement membrane.

  6. Outcomes after breast conservation treatment with radiation in women with ductal carcinoma in situ and prior nonbreast malignancy.

    PubMed

    Shah, Deepika N; Vapiwala, Neha; Solin, Lawrence J

    2009-01-01

    Management of ductal carcinoma in situ (DCIS) of the breast is controversial, as not all patients progress to invasive carcinoma. This report analyzes the outcomes after breast conservation treatment (BCT) with radiation in patients with DCIS following prior malignancy at another anatomic site. The study cohort was comprised of 14 women with DCIS who were treated between 1978 and 2003. The median age at diagnosis of DCIS was 54 years (mean 56; range 37-78) and for the prior nonbreast malignancy was 44 years (mean 47; range 27-76). All patients underwent breast conservation surgery followed by whole breast radiation and tumor bed boost. The median and mean follow-up times after treatment of DCIS were 8.0 and 9.1 years, respectively (range 2-18). The median and mean interval period between the prior malignancy and DCIS was 6.0 and 8.2 years, respectively (range 1-30). There was one (7%) local failure, two (14%) contralateral breast cancers, and one (7%) death from breast cancer that occurred 7 years after BCT following contralateral invasive breast cancer. In this cohort of 14 patients treated for DCIS of the breast after a prior nonbreast malignancy, treatment for DCIS resulted in a high rate of local control and should be considered for curative intent.

  7. Computational Simulation of Breast Compression Based on Segmented Breast and Fibroglandular Tissues on Magnetic Resonance Images

    PubMed Central

    Shih, Tzu-Ching; Chen, Jeon-Hor; Liu, Dongxu; Nie, Ke; Sun, Lizhi; Lin, Muqing; Chang, Daniel; Nalcioglu, Orhan; Su, Min-Ying

    2010-01-01

    This study presents a finite element based computational model to simulate the three-dimensional deformation of the breast and the fibroglandular tissues under compression. The simulation was based on 3D MR images of the breast, and the craniocaudal and mediolateral oblique compression as used in mammography was applied. The geometry of whole breast and the segmented fibroglandular tissues within the breast were reconstructed using triangular meshes by using the Avizo® 6.0 software package. Due to the large deformation in breast compression, a finite element model was used to simulate the non-linear elastic tissue deformation under compression, using the MSC.Marc® software package. The model was tested in 4 cases. The results showed a higher displacement along the compression direction compared to the other two directions. The compressed breast thickness in these 4 cases at 60% compression ratio was in the range of 5-7 cm, which is the typical range of thickness in mammography. The projection of the fibroglandular tissue mesh at 60% compression ratio was compared to the corresponding mammograms of two women, and they demonstrated spatially matched distributions. However, since the compression was based on MRI, which has much coarser spatial resolution than the in-plane resolution of mammography, this method is unlikely to generate a synthetic mammogram close to the clinical quality. Whether this model may be used to understand the technical factors that may impact the variations in breast density measurements needs further investigation. Since this method can be applied to simulate compression of the breast at different views and different compression levels, another possible application is to provide a tool for comparing breast images acquired using different imaging modalities – such as MRI, mammography, whole breast ultrasound, and molecular imaging – that are performed using different body positions and different compression conditions. PMID:20601773

  8. Computational simulation of breast compression based on segmented breast and fibroglandular tissues on magnetic resonance images

    NASA Astrophysics Data System (ADS)

    Shih, Tzu-Ching; Chen, Jeon-Hor; Liu, Dongxu; Nie, Ke; Sun, Lizhi; Lin, Muqing; Chang, Daniel; Nalcioglu, Orhan; Su, Min-Ying

    2010-07-01

    This study presents a finite element-based computational model to simulate the three-dimensional deformation of a breast and fibroglandular tissues under compression. The simulation was based on 3D MR images of the breast, and craniocaudal and mediolateral oblique compression, as used in mammography, was applied. The geometry of the whole breast and the segmented fibroglandular tissues within the breast were reconstructed using triangular meshes by using the Avizo® 6.0 software package. Due to the large deformation in breast compression, a finite element model was used to simulate the nonlinear elastic tissue deformation under compression, using the MSC.Marc® software package. The model was tested in four cases. The results showed a higher displacement along the compression direction compared to the other two directions. The compressed breast thickness in these four cases at a compression ratio of 60% was in the range of 5-7 cm, which is a typical range of thickness in mammography. The projection of the fibroglandular tissue mesh at a compression ratio of 60% was compared to the corresponding mammograms of two women, and they demonstrated spatially matched distributions. However, since the compression was based on magnetic resonance imaging (MRI), which has much coarser spatial resolution than the in-plane resolution of mammography, this method is unlikely to generate a synthetic mammogram close to the clinical quality. Whether this model may be used to understand the technical factors that may impact the variations in breast density needs further investigation. Since this method can be applied to simulate compression of the breast at different views and different compression levels, another possible application is to provide a tool for comparing breast images acquired using different imaging modalities--such as MRI, mammography, whole breast ultrasound and molecular imaging--that are performed using different body positions and under different compression

  9. 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

  10. [DNA aptamers selection for breast cancer].

    PubMed

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

    2016-05-01

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

  11. 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

  12. 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.

  13. Incidental Breast Lesions Identified by 18F-FDG PET/CT: Which Clinical Variables Differentiate between Benign and Malignant Breast Lesions?

    PubMed Central

    Shin, Kyung Min; Jung, Su Jin; Lim, Hyo Soon; Lee, Sang Woo; Cho, Seung Hyun; Jang, Yun-Jin; Lee, Hui Joong; Kim, Gab Chul; Jung, Jin Hyang; Park, Ji Young

    2015-01-01

    Purpose The aim of our study was to evaluate the risk of malignancy and to determine which clinical variables differentiate between benign and malignant focal breast lesions found incidentally on 18F-flourodeoxyglucose positron emission tomography and computed tomography (FDG PET/CT). Methods From March 2005 to October 2011, 21,224 women with no history of breast cancer underwent FDG PET/CT at three university-affiliated hospitals. We retrospectively identified 214 patients with incidental focal hypermetabolic breast lesions and grouped them into benign and malignant lesion groups. Of the 214 patients, 82 patients with 91 lesions were included in this study. All lesions were confirmed histologically or were assessed by follow-up imaging for greater than 2 years. The patient age, maximum standardized uptake value (SUVmax), lesion size on ultrasonography (US), and Breast Imaging-Reporting and Data System (BI-RADS) category on US in conjunction with mammography were compared between the groups. Multivariate logistic regression analysis was used to identify independent factors associated with malignancy. Results The risk of malignancy was 29.7% (27/91) in breast incidentalomas detected by FDG PET/CT. The univariate analysis showed that the patient age, SUVmax, tumor size, and BI-RADS category differed significantly between the malignant and benign groups. The multivariate analysis showed that the BI-RADS category was the only significant factor differentiating benign from malignant lesions (p=0.002). Conclusion BIRADS category based on US in conjunction with mammography was the only useful tool to differentiate between malignant and benign lesions in breast incidentalomas on FDG PET/CT. PMID:25834614

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

    PubMed Central

    2014-01-01

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

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

    PubMed

    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.

  16. 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

  17. 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

  18. Evolving concepts: how diet and the intestinal microbiome act as modulators of breast malignancy.

    PubMed

    Shapira, Iuliana; Sultan, Keith; Lee, Annette; 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

  19. 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.

  20. Toward Carbon-Nanotube-Based Theranostic Agents for Microwave Detection and Treatment of Breast Cancer: Enhanced Dielectric and Heating Response of Tissue-Mimicking Materials

    PubMed Central

    Mashal, Alireza; Sitharaman, Balaji; Li, Xu; Avti, Pramod; Sahakian, Alan V.; Booske, John H.; Hagness, Susan C.

    2010-01-01

    The experimental results reported in this letter suggest that single-walled carbon nanotubes (SWCNTs) have the potential to enhance dielectric contrast between malignant and normal tissue for microwave detection of breast cancer and facilitate selective heating of malignant tissue for microwave hyperthermia treatment of breast cancer. In this study, we constructed tissue-mimicking materials with varying concentrations of SWCNTs and characterized their dielectric properties and heating response. At SWCNT concentrations of less than 0.5% by weight, we observed significant increases in the relative permittivity and effective conductivity. In microwave heating experiments, we observed significantly greater temperature increases in mixtures containing SWCNTs. These temperature increases scaled linearly with the effective conductivity of the mixtures. This work is a first step towards the development of functionalized, tumor-targeting SWCNTs as theranostic (integrated therapeutic and diagnostic) agents for microwave breast cancer detection and treatment. PMID:20176534

  1. Independent predictors of breast malignancy in screen-detected microcalcifications: biopsy results in 2545 cases

    PubMed Central

    Farshid, G; Sullivan, T; Downey, P; Gill, P G; Pieterse, S

    2011-01-01

    Background: Mammographic microcalcifications are associated with many benign lesions, ductal carcinoma in situ (DCIS) and invasive cancer. Careful assessment criteria are required to minimise benign biopsies while optimising cancer diagnosis. We wished to evaluate the assessment outcomes of microcalcifications biopsied in the setting of population-based breast cancer screening. Methods: Between January 1992 and December 2007, cases biopsied in which microcalcifications were the only imaging abnormality were included. Patient demographics, imaging features and final histology were subjected to statistical analysis to determine independent predictors of malignancy. Results: In all, 2545 lesions, with a mean diameter of 21.8 mm (s.d. 23.8 mm) and observed in patients with a mean age of 57.7 years (s.d. 8.4 years), were included. Using the grading system adopted by the RANZCR, the grade was 3 in 47.7% 4 in 28.3% and 5 in 24.0%. After assessment, 1220 lesions (47.9%) were malignant (809 DCIS only, 411 DCIS with invasive cancer) and 1325 (52.1%) were non-malignant, including 122 (4.8%) premalignant lesions (lobular carcinoma in situ, atypical lobular hyperplasia and atypical ductal hyperplasia). Only 30.9% of the DCIS was of low grade. Mammographic extent of microcalcifications >15 mm, imaging grade, their pattern of distribution, presence of a palpable mass and detection after the first screening episode showed significant univariate associations with malignancy. On multivariate modeling imaging grade, mammographic extent of microcalcifications >15 mm, palpable mass and screening episode were retained as independent predictors of malignancy. Radiological grade had the largest effect with lesions of grade 4 and 5 being 2.2 and 3.3 times more likely to be malignant, respectively, than grade 3 lesions. Conclusion: The radiological grading scheme used throughout Australia and parts of Europe is validated as a useful system of stratifying microcalcifications into

  2. [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.

  3. Malignant fibrous histiocytoma of the breast. A case report and review of the literature

    SciTech Connect

    Langham, M.R. Jr.; Mills, A.S.; DeMay, R.M.; O'Dowd, G.J.; Grathwohl, M.A.; Horsley, J.S.

    1984-08-01

    The clinicopathologic features of a malignant fibrous histiocytoma arising in a female breast are presented. Seven cases have been previously reported. These may be divided into three subgroups based on history and pathologic findings. Three of the seven occurred in women without a history of other tumors or previous irradiation. One appeared with a cystosarcoma phyllodes, and three arose following radiation for carcinoma of the breast. The patient in this study had received no radiation. Treatment has been based on surgical resection; the roles of chemotherapy and radiation are uncertain. Although resection alone in the first subgroup has lead to no reported mortality, the small number of cases and the relatively short follow-up does not allow a meaningful assessment of the prognosis in this disease.

  4. 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

  5. Clinical application of shear wave elastography (SWE) in the diagnosis of benign and malignant breast diseases.

    PubMed

    Chang, Jung Min; Moon, Woo Kyung; Cho, Nariya; Yi, Ann; Koo, Hye Ryoung; Han, Wonsik; Noh, Dong-Young; Moon, Hyeong-Gon; Kim, Seung Ja

    2011-08-01

    Shear wave elastography (SWE) is an emerging technique which can obtain quantitative elasticity values in breast disease. We therefore evaluated the diagnostic performance of SWE for the differentiation of breast masses compared with conventional ultrasound (US). Conventional US and SWE were performed by three experienced radiologists for 158 consecutive women who had been scheduled for US-guided core biopsy or surgical excision in 182 breast masses (89 malignancies and 93 benign; mean size, 1.76 cm). For each lesion, quantitative elasticity was measured in terms of the Young's modulus (in kilopascals, kPa) with SWE, and BI-RADS final categories were assessed with conventional US. The mean elasticity values were significantly higher in malignant masses (153.3 kPa ± 58.1) than in benign masses (46.1 kPa ± 42.9), (P < 0.0001). The average mean elasticity values of invasive ductal (157.5 ± 57.07) or invasive lobular (169.5 ± 61.06) carcinomas were higher than those of ductal carcinoma in situ (117.8 kPa ± 54.72). The average mean value was 49.58 ± 43.51 for fibroadenoma, 35.3 ± 31.2 for fibrocystic changes, 69.5 ± 63.2 for intraductal papilloma, and 149.5 ± 132.4 for adenosis or stromal fibrosis. The optimal cut-off value, yielding the maximal sum of sensitivity and specificity, was 80.17 kPa, and the sensitivity and specificity of SWE were 88.8% (79 of 89) and 84.9% (79 of 93). The area under the ROC curve (Az value) was 0.898 for conventional US, 0.932 for SWE, and 0.982 for combined data. In conclusion, there were significant differences in the elasticity values of benign and malignant masses as well as invasive and intraductal cancers with SWE. Our results suggest that SWE has the potential to aid in the differentiation of benign and malignant breast lesions.

  6. Intracystic mural nodules of the breast: benign versus malignant; a multidisciplinary imaging and management approach.

    PubMed

    Ferguson, Melissa J

    2015-06-01

    This case report illustrates the presence of intracystic mural nodules within the breast, a benign proliferative disorder associated with the fibrocystic spectrum: papillary apocrine metaplasia. The aim of this paper is to provide a comprehensive understanding of the physical and histological attributes of benign intracystic mural nodules, and the ability to distinguish these from a malignant papilloma and carcinoma. Also, the technical and patient considerations, as well as the appropriate imaging and interventional methods required to ensure correct patient management pathway are discussed, extending into an analysis of the psychological effects felt by patients undergoing assessment.

  7. Management of malignant pleural effusion secondary to breast cancer: talc pleurodesis and pleuroperitoneal shunting.

    PubMed

    Saute, M

    1995-01-01

    Malignant pleural effusion is a frequent complication of metastatic breast cancer, leading to a significant degree of morbidity. Drainage of the effusion by thoracocentesis and subsequent pleurodesis is an established means of symptomatic relief in these patients. Several sclerosing agents have been reported in the literature, including doxycylin, minocyclin, tetracyclines, bleomycin, cisplatin, etoposide, fluorouracil, interferon-beta, Corynebacterium parvum, and talc which gives the best results. The condition of the lung's parenchyma must be evaluated prior to the procedure to rule out lymphangitis carcinomatosa or bronchial obstruction that would impair the expansion of the lung. In these situations, the implantation of a pleuroperitoneal shunt is an alternative to be considered. PMID:7744586

  8. miR-21 induces myofibroblast differentiation and promotes the malignant progression of breast phyllodes tumors.

    PubMed

    Gong, Chang; Nie, Yan; Qu, Shaohua; Liao, Jian-You; Cui, Xiuying; Yao, Herui; Zeng, Yunjie; Su, Fengxi; Song, Erwei; Liu, Qiang

    2014-08-15

    Phyllodes tumors of breast, even histologically diagnosed as benign, can recur locally and have metastatic potential. Histologic markers only have limited value in predicting the clinical behavior of phyllodes tumors. It remains unknown what drives the malignant progression of phyllodes tumors. We found that the expression of myofibroblast markers, α-smooth muscle actin (α-SMA), fibroblast activation protein (FAP), and stromal cell-derived factor-1 (SDF-1), is progressively increased in the malignant progression of phyllodes tumors. Microarray showed that miR-21 was one of the most significantly upregulated microRNAs in malignant phyllodes tumors compared with benign phyllodes tumors. In addition, increased miR-21 expression was primarily localized to α-SMA-positive myofibroblasts. More importantly, α-SMA and miR-21 are independent predictors of recurrence and metastasis, with their predictive value of recurrence better than histologic grading. Furthermore, miR-21 mimics promoted, whereas miR-21 antisense oligos inhibited, the expression of α-SMA, FAP, and SDF-1, as well as the proliferation and invasion of primary stromal cells of phyllodes tumors. The ability of miR-21 to induce myofibroblast differentiation was mediated by its regulation on Smad7 and PTEN, which regulate the migration and proliferation, respectively. In breast phyllodes tumor xenografts, miR-21 accelerated tumor growth, induced myofibroblast differentiation, and promoted metastasis. This study suggests an important role of myofibroblast differentiation in the malignant progression of phyllodes tumors that is driven by increased miR-21.

  9. Differential CARM1 Isoform Expression in Subcellular Compartments and among Malignant and Benign Breast Tumors

    PubMed Central

    Shlensky, David; Mirrielees, Jennifer A.; Zhao, Zibo; Wang, Lu; Mahajan, Aparna; Yu, Menggang; Sherer, Nathan M.; Wilke, Lee G.; Xu, Wei

    2015-01-01

    Purpose Coactivator-associated arginine methyltransferase 1 (CARM1) is a coactivator for ERα and cancer-relevant transcription factors, and can methylate diverse cellular targets including histones. CARM1 is expressed in one of two alternative splice isoforms, full-length CARM1 (CARM1FL) and truncated CARM1 (CARM1ΔE15). CARM1FL and CARM1ΔE15 function differently in transcriptional regulation, protein methylation, and mediation of pre-mRNA splicing in cellular models. Methods To investigate the functional roles and the prognosis potential of CARM1 alternative spliced isoforms in breast cancer, we used recently developed antibodies to detect differential CARM1 isoform expression in subcellular compartments and among malignant and benign breast tumors. Results Immunofluorescence in MDA-MB-231 and BG-1 cell lines demonstrated that CARM1ΔE15 is the dominant isoform expressed in the cytoplasm, and CARM1FL is more nuclear localized. CARM1ΔE15 was found to be more sensitive to Hsp90 inhibition than CARM1FL, indicating that the truncated isoform may be the oncogenic form. Clinical cancer samples did not have significantly higher expression of CARM1FL or CARM1ΔE15 than benign breast samples at the level of mRNA or histology. Furthermore neither CARM1FL nor CARM1ΔE15 expression correlated with breast cancer molecular subtypes, tumor size, or lymph node involvement. Conclusions The analysis presented here lends new insights into the possible oncogenic role of CARM1ΔE15. This study also demonstrates no obvious association of CARM1 isoform expression and clinical correlates in breast cancer. Recent studies, however, have shown that CARM1 expression correlates with poor prognosis, indicating a need for further studies of both CARM1 isoforms in a large cohort of breast cancer specimens. PMID:26030442

  10. 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.

  11. 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.

  12. Automated algorithm for breast tissue differentiation in optical coherence tomography

    PubMed Central

    Mujat, Mircea; Ferguson, R. Daniel; Hammer, Daniel X.; Gittins, Christopher; Iftimia, Nicusor

    2010-01-01

    An automated algorithm for differentiating breast tissue types based on optical coherence tomography (OCT) data is presented. Eight parameters are derived from the OCT reflectivity profiles and their means and covariance matrices are calculated for each tissue type from a training set (48 samples) selected based on histological examination. A quadratic discrimination score is then used to assess the samples from a validation set. The algorithm results for a set of 89 breast tissue samples were correlated with the histological findings, yielding specificity and sensitivity of 0.88. If further perfected to work in real time and yield even higher sensitivity and specificity, this algorithm would be a valuable tool for biopsy guidance and could significantly increase procedure reliability by reducing both the number of nondiagnostic aspirates and the number of false negatives. PMID:19566332

  13. Salivary gland-type tumors of the breast: a spectrum of benign and malignant tumors including "triple negative carcinomas" of low malignant potential.

    PubMed

    Foschini, Maria P; Krausz, Thomas

    2010-02-01

    Salivary gland-type neoplasms of the breast are uncommon and comprise numerous entities analogous to that more commonly seen in salivary glands. The clinicopathologic spectrum ranges from benign to malignant but there are important differences as compared with those of their salivary counterpart. In the breast, benign adenomyoepithelioma is recognized in addition to malignant one, whereas in the salivary gland a histologically similar tumor is designated as epithelial-myoepithelial carcinoma without a separate benign subgroup. Mammary adenoid cystic carcinoma is a low-grade neoplasm compared with its salivary equivalent. It is also important to appreciate that in contrast to "triple negative" conventional breast carcinomas with aggressive course, most salivary-type malignant breast neoplasms behave in a low-grade manner. Most of these tumors are capable of differentiating along both epithelial and myoepithelial lines, but the amount of each lineage-component varies from case to case, contributing to diagnostic difficulties. Well established examples of this group include pleomorphic adenoma, adenomyoepithelioma, and adenoid cystic carcinoma. Another family of salivary gland-type mammary epithelial neoplasms is devoid of myoepithelial cells. Key examples include mucoepidermoid carcinoma and acinic cell carcinoma. The number of cases of salivary gland-type mammary neoplasms in the published data is constantly increasing but some of the rarest subtypes like polymorphous low-grade adenocarcinoma and oncocytic carcinoma are "struggling" to become clinically relevant entities in line with those occurring more frequently in salivary glands.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. Breast Tissue Characterization with Photon-counting Spectral CT Imaging: A Postmortem Breast Study

    PubMed Central

    Ding, Huanjun; Klopfer, Michael J.; Ducote, Justin L.; Masaki, Fumitaro

    2014-01-01

    Purpose To investigate the feasibility of breast tissue characterization in terms of water, lipid, and protein contents with a spectral computed tomographic (CT) system based on a cadmium zinc telluride (CZT) photon-counting detector by using postmortem breasts. Materials and Methods Nineteen pairs of postmortem breasts were imaged with a CZT-based photon-counting spectral CT system with beam energy of 100 kVp. The mean glandular dose was estimated to be in the range of 1.8–2.2 mGy. The images were corrected for pulse pile-up and other artifacts by using spectral distortion corrections. Dual-energy decomposition was then applied to characterize each breast into water, lipid, and protein contents. The precision of the three-compartment characterization was evaluated by comparing the composition of right and left breasts, where the standard error of the estimations was determined. The results of dual-energy decomposition were compared by using averaged root mean square to chemical analysis, which was used as the reference standard. Results The standard errors of the estimations of the right-left correlations obtained from spectral CT were 7.4%, 6.7%, and 3.2% for water, lipid, and protein contents, respectively. Compared with the reference standard, the average root mean square error in breast tissue composition was 2.8%. Conclusion Spectral CT can be used to accurately quantify the water, lipid, and protein contents in breast tissue in a laboratory study by using postmortem specimens. © RSNA, 2014 PMID:24814180

  1. 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

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

    PubMed

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

    2002-02-01

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

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

    PubMed

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

    2015-12-01

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

  4. Bacterial floras and biofilms of malignant wounds associated with breast cancers.

    PubMed

    Fromantin, Isabelle; Seyer, Damien; Watson, Sarah; Rollot, Florence; Elard, Jacqueline; Escande, Marie Christine; De Rycke, Yann; Kriegel, Irène; Larreta Garde, Véronique

    2013-10-01

    The risk of infections and the appearance of symptoms (e.g., odors) represent the main troubles resulting from malignant wounds. The aim of this study was to characterize the balance of bacterial floras and the relationships between biofilms and bacteria and the emergence of symptoms. Experimental research was carried out for 42 days on malignant wounds associated with breast cancer. Investigations of bacterial floras (aerobes, aero-anaerobes, and anaerobes), detection of the presence of biofilms by microscopic epifluorescence, and clinical assessment were performed. We characterized biofilms in 32 malignant wounds associated with breast cancer and bacterial floras in 25 such wounds. A mixed group of floras, composed of 54 different bacterial types, was identified, with an average number per patient of 3.6 aerobic species and 1.7 anaerobic species; the presence of strict anaerobic bacterial strains was evidenced in 70% of the wounds; biofilm was observed in 35% of the cases. Odor was a reliable indicator of colonization by anaerobes, even when this symptom was not directly linked to any of the identified anaerobic bacteria. Bacteria are more likely to be present during myelosuppression and significantly increase the emergence of odors and pain when present at amounts of >10(5) · g(-1). The presence of biofilms was not associated with clinical signs or with precise types of bacteria. No infections occurred during the 42-day evaluation period. This study provides a dynamic description of the bacterial floras of tumoral wounds. The study results highlight the absolute need for new therapeutic options that are effective for use on circulating bacteria as well as on bacteria organized in biofilm.

  5. The Cytological Grading of Malignant Neoplasms of The Breast and Its Correlation With The Histological Grading

    PubMed Central

    Vasudev, Vidya; R., Rangaswamy; V., Geethamani

    2013-01-01

    Background and Objectives: Breast carcinoma is one of the leading causes of malignancy in females. The diagnosis of breast carcinoma is often made by fine needle aspiration cytology. Nuclear grading is an important prognostic factor. It is important to grade breast carcinomas, which will provide valuable information to the treating oncologists to plan their management. The purpose of this study was to compare the cytological grading and typing with the histological grading and typing and the regional lymph node metastasis. Methodology: This retrospective and prospective study was done on 60 cases with malignant and suspicious diagnoses on FNAC, which had histopathological correlations, from January 2004 to December 2007. The cytological grading was done by Robinson's Method and the histopathological grading was done by the modified Scarff Bloom Richardson method. Cytological and histological typings were also done. The statistical analysis was done by using the SPSS software: The Chi square test was used and a contingency tale analysis (cross tabs procedure) was also done. Results: The cytohistological grading correlation was accurate in 7 cases (100%) of grade 1, 22 cases (71%) of grade 3 and 9 cases (42.9%) of grade 2 cancers. The accuracy was 62.7% (P < 0.001). A higher cytological grade was associated with a nodal metastasis. (cc : 0.399, P < .006) The cytological typing was accurate in 44 cases out of the 60 cases. Interpretation and Conclusion: The cytological grade correlated well with the histological grading accuracy (62.7%) and a higher grade was associated with a nodal metastasis (P < 0.006), Hence the cytological grading and typing should be routinely incorporated in the cytology reports and they can be of great value in guiding the choice of the treatment protocols. PMID:23905097

  6. Relationship between cathepsin D, urokinase, and plasminogen activator inhibitors in malignant vs benign breast tumours.

    PubMed Central

    Foucré, D.; Bouchet, C.; Hacène, K.; Pourreau-Schneider, N.; Gentile, A.; Martin, P. M.; Desplaces, A.; Oglobine, J.

    1991-01-01

    The concentrations of cathepsin D (Cath D), urokinase (uPA) and two plasminogen activator inhibitors (PAI-1 and PAI-2) were analysed in the cytosols of 130 human mammary tumours (43 benign tumours and 87 primary and unilateral breast carcinomas). uPA, PAI-1 and PAI-2 levels were measured by antigenic immunoassays and Cath D by immunoradiometric assay. The median levels of the four parameters were significantly higher in the malignant tumours than in the benign ones. Cath D and uPA increases were 4-fold and 5-fold respectively. PAI-1 and PAI-2 increases were much more important, 74-fold and 29-fold respectively. In malignant tumours, median levels of Cath D and uPA did not vary according to classical prognostic factors (histologic grade, presence or absence of axillary lymph nodes, steroid receptors, UICC stage, tumour size, age, and menopausal status). However, PAI-1 decreased in ER+ and PR+ tumours and PAI-2 increased in menopausal women's tumours. When Cath D, uPA, PAI-1 and PAI-2 levels in malignant tumours were compared, positive correlations were found for all combinations. The implication of plasminogen activator inhibitors in the phenomenon was surprising and merits further investigation using tools other than global antigen measurements in tumours. PMID:1931618

  7. 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

  8. 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

  9. Relationship between breast cancer and thyroid disease: relevance of autoimmune thyroid disorders in breast malignancy.

    PubMed

    Giani, C; Fierabracci, P; Bonacci, R; Gigliotti, A; Campani, D; De Negri, F; Cecchetti, D; Martino, E; Pinchera, A

    1996-03-01

    The relationship between thyroid dysfunction and breast cancer (BC) is debated. To clarify this controversial issue, a prospective study on thyroid function in BC was performed. The prevalence of thyroid disease was examined in 102 consecutive BC patients with ductal infiltrating carcinoma after surgery and before starting any chemohormonal or x-ray therapy and in 100 age-matched control healthy women living in the same borderline iodine-sufficient geographic area. All subjects were submitted to clinical ultrasound thyroid evaluation and serum free T4, free T3, TSH, thyroperoxidase antibody, and thyroglobulin antibody determination. Fine needle aspiration was performed in all thyroid nodules. Estrogen and progesterone receptors (ER and PR, respectively) were assayed in 92 and 55 BC specimens, respectively. The overall prevalence of thyroid disease was 47 in 102 (46%) in BC patients and 14 in 100 (14%) in controls (P < 0.0001). The prevalence of nontoxic goiter was 27.4% in BC patients and 11% in controls (P = 0.003). Hashimoto's thyroiditis was found in 13.7% of BC patients and in only 2% of the controls (P < 0.005). Other thyroid disorders found in the BC group included 2 cases of Graves' disease, 2 of thyroid carcinoma, and 1 of subacute thyroiditis, whereas in the control group only 1 case of Graves' disease and none of the other disorders were found. Mean free T3, free T4, and TSH concentrations showed no difference between BC patients and controls. The prevalence of thyroperoxidase antibody was higher in BC patients than in controls (23.5% vs. 8%; P < 0.005), whereas the prevalence of thyroglobulin antibody was not different. In BC patients the presence of thyroid antibodies was more frequently associated with clinically detectable autoimmune thyroiditis (14 of 26, 51.8%; P = 0.03) and was more common in the younger group. The positivity of ER was found in 51 of 92 (55.43%) and that of PR was found in 26 of 55 (47.27%) BC specimens. No relationship was found

  10. 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.

  11. [Extracting and study of biochemical properties of thiamine pyrophosphokinase from non-malignant and tumor tissue of myometrium].

    PubMed

    Orishaka, O V; Vovchuk, I L; Petrov, S A

    2014-01-01

    The method of extraction and purification of thiamine pyrophosphokinase from non-malignant and tumor tissue of myometrium has been elaborated. Kinetic characteristics of T-kinase from non-malignant and tumor tissue of women myometrium have been studied. It has been shown, that malignization of myometrium is accompanied by a decrease in affinity of thiamine pyrophosphokinase from tumor to thiamine and by an increase in sensitivity of the enzyme from tumor to thiochrome.

  12. A two-dimensional locally regularized strain estimation technique: preliminary clinical results for the assessment of benign and malignant breast lesions

    NASA Astrophysics Data System (ADS)

    Brusseau, Elisabeth; Detti, Valérie; Coulon, Agnès; Maissiat, Emmanuèle; Boublay, Nawèle; Berthezène, Yves; Fromageau, Jérémie; Bush, Nigel; Bamber, Jeffrey

    2011-03-01

    We previously developed a 2D locally regularized strain estimation technique that was already validated with ex vivo tissues. In this study, our technique is assessed with in vivo data, by examining breast abnormalities in clinical conditions. Method reliability is analyzed as well as tissue strain fields according to the benign or malignant character of the lesion. Ultrasound RF data were acquired in two centers on ten lesions, five being classified as fibroadenomas, the other five being classified as malignant tumors, mainly ductal carcinomas from grades I to III. The estimation procedure we developed involves maximizing a similarity criterion (the normalized correlation coefficient or NCC) between pre- and post-compression images, the deformation effects being considered. The probability of correct strain estimation is higher if this coefficient is closer to 1. Results demonstrated the ability of our technique to provide good-quality strain images with clinical data. For all lesions, movies of tissue strain during compression were obtained, with strains that can reach 15%. The NCC averaged over each movie was computed, leading for the ten cases to a mean value of 0.93, a minimum value of 0.87 and a maximum value of 0.98. These high NCC values confirm the reliability of the strain estimation. Moreover, lesions were clearly identified for the ten cases investigated. Finally, we have observed with malignant lesions that compared to ultrasound data, strain images can put in relief a more important lesion size, and can help in evaluating the lesion invasive character.

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

    PubMed

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

    2001-06-01

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

  14. Identification of different subtypes of breast cancer using tissue microarray.

    PubMed

    Munirah, M A; Siti-Aishah, M A; Reena, M Z; Sharifah, N A; Rohaizak, M; Norlia, A; Rafie, M K M; Asmiati, A; Hisham, A; Fuad, I; Shahrun, N S; Das, S

    2011-01-01

    Breast cancer may be classified into luminal A, luminal B, HER2+/ER-, basal-like and normal-like subtypes based on gene expression profiling or immunohistochemical (IHC) characteristics. The main aim of the present study was to classify breast cancer into molecular subtypes based on immunohistochemistry findings and correlate the subtypes with clinicopathological factors. Two hundred and seventeen primary breast carcinomas tumor tissues were immunostained for ER, PR, HER2, CK5/6, EGFR, CK8/18, p53 and Ki67 using tissue microarray technique. All subtypes were significantly associated with Malay ethnic background (p=0.035) compared to other racial origins. The most common subtypes of breast cancers were luminal A and was significantly associated with low histological grade (p<0.000) and p53 negativity (p=0.003) compared to HER2+/ER-, basal-like and normal-like subtypes with high histological grade (p<0.000) and p53 positivity (p=0.003). Luminal B subtype had the smallest mean tumor size (p=0.009) and also the highest mean number of lymph nodes positive (p=0.032) compared to other subtypes. All markers except EGFR and Ki67 were significantly associated with the subtypes. The most common histological type was infiltrating ductal carcinoma, NOS. Majority of basal-like subtype showed comedo-type necrosis (68.8%) and infiltrative margin (81.3%). Our studies suggest that IHC can be used to identify the different subtypes of breast cancer and all subtypes were significantly associated with race, mean tumor size, mean number of lymph node positive, histological grade and all immunohistochemical markers except EGFR and Ki67.

  15. MLK3 is critical for breast cancer cell migration and promotes a malignant phenotype in mammary epithelial cells.

    PubMed

    Chen, J; Miller, E M; Gallo, K A

    2010-08-01

    The malignant phenotype in breast cancer is driven by aberrant signal transduction pathways. Mixed-lineage kinase-3 (MLK3) is a mammalian mitogen-activated protein kinase kinase kinase (MAP3K) that activates multiple MAPK pathways. Depending on the cellular context, MLK3 has been implicated in apoptosis, proliferation, migration and differentiation. Here we investigated the effect of MLK3 and its signaling to MAPKs in the acquisition of malignancy in breast cancer. We show that MLK3 is highly expressed in breast cancer cells. We provide evidence that MLK3's catalytic activity and signaling to c-jun N-terminal kinase (JNK) is required for migration of highly invasive breast cancer cells and for MLK3-induced migration of mammary epithelial cells. Expression of active MLK3 is sufficient to induce the invasion of mammary epithelial cells, which requires AP-1 activity and is accompanied by the expression of several proteins corresponding to AP-1-regulated invasion genes. To assess MLK3's contribution to the breast cancer malignant phenotype in a more physiological setting, we implemented a strategy to inducibly express active MLK3 in the preformed acini of MCF10A cells grown in 3D Matrigel. Induction of MLK3 expression dramatically increases acinar size and modestly perturbs apicobasal polarity. Remarkably, MLK3 expression induces luminal repopulation and suppresses the expression of the pro-apoptotic protein BimEL, as has been observed in Her2/Neu-expressing acini. Taken together, our data show that MLK3-JNK-AP-1 signaling is critical for breast cancer cell migration and invasion. Our current study uncovers both a proliferative and novel antiapoptotic role for MLK3 in the acquisition of a malignant phenotype in mammary epithelial cells. Thus, MLK3 may be an important therapeutic target for the treatment of invasive breast cancer.

  16. 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. PMID:27630925

  17. 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.

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

    PubMed

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

    2016-07-01

    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. PMID:27630925

  19. 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.

  20. Serum and tissue PIVKA-II expression reflect the biological malignant potential of small hepatocellular carcinoma.

    PubMed

    Tamano, Masaya; Sugaya, Hitoshi; Oguma, Motoo; Iijima, Makoto; Yoneda, Masashi; Murohisa, Toshimitsu; Kojima, Kazuo; Kuniyoshi, Toru; Majima, Yuichi; Hashimoto, Takashi; Terano, Akira

    2002-04-01

    A sensitive method for measuring the serum level of protein-induced by vitamin K absence or antagonist II (PIVKA-II) has become so widely available that it is now used for the clinical diagnosis of small hepatocellular carcinoma (HCC). It is known that serum PIVKA-II can be a prognostic indicator for HCC, but there have been no detailed investigations concerning the tissue expression of PIVKA-II. The present study assessed the relationship between serum or tissue PIVKA-II and the biological malignant potential of HCC. The subjects were 25 patients with histologically confirmed HCC, that were solitary and 3 cm or less in diameter. Tissue PIVKA-II was detected by immunostaining using MU-3 as the primary antibody. The biological malignant potential of the tumors was evaluated on the basis of the Ki-67 labeling index of HCC cells and the tumor arterial vascularity assesed by angiography and CO(2) enhanced ultrasonography. The recurrence-free period after treatment was also evaluated. Among the 25 patients, eight were positive for tissue PIVKA-II. Serum PIVKA-II levels were significantly higher in the tissue PIVKA-II-positive patients compared with the negative patients, but serum and tissue PIVKA-II expressions were not consistently parallel. Tumor cell proliferation was closely correlated with the tissue PIVKA-II expression, while the recurrence-free period was correlated with the serum PIVKA-II level. Tumor arterial vascularity showed a strong correlation with the expression of both serum and tissue PIVKA-II. In conclusion, serum and tissue PIVKA-II expression reflect the biological malignant potential of HCC and thus may be useful indicators for the prognosis of small HCC.

  1. 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

  2. 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.

  3. 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

  4. Quantitative analysis of peri-tumor tissue elasticity based on shear-wave elastography for breast tumor classification.

    PubMed

    Xiao, Yang; Zeng, Jie; Qian, Ming; Zheng, Rongqin; Zheng, Hairong

    2013-01-01

    For shear-wave elastography (SWE) images, the most common site of tumor-associated stiffness is generally in the surrounding stroma rather than the tumor itself. The aim of this study is to assess the value of the peri-tumor tissue elasticity in the classification of breast tumors. SWE images of 106 breast tumors (65 benign, 41 malignant) were collected from 82 consecutive patients. By applying the image processing method, 5 elastographic features of the peri-tumor area (elasticity modulus mean, maximum, standard deviation, hardness degree and elasticity ratio) were computed to represent peri-tumor tissue elasticity. B-mode Breast Imaging Reporting and Data System (BI-RADS) were used for comparing the diagnostic performances between the grayscale US and color SWE images. Histopathologic results were used as the reference standard. The t-test, point biserial correlation coefficient and receiver operating characteristic (ROC) curve analysis were performed for statistical analysis. As a result, the Az values (area under ROC curve) were 0.92, 0.95, 0.94, 0.91, and 0.98 for the classifiers using the five elastographic features respectively, and 0.91 for BI-RADS assessment. The results showed that the peri-tumor tissue elasticity could provide valuable information for breast tumor classification.

  5. 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

  6. 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

  7. 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.

  8. Folate receptors in malignant and benign tissues of human female genital tract.

    PubMed

    Holm, J; Hansen, S I; Høier-Madsen, M; Helkjaer, P E; Nichols, C W

    1997-08-01

    We have characterized the folate receptor in malignant and benign tissues of human female genital tract (Fallopian tube and benign and malignant tissues of uterus). Radioligand binding displayed characteristics similar to those of other folate binding proteins. Those include a high-affinity type of binding (K = 10(10)M-1), apparent positive cooperativity, a slow dissociation at pH 7.4 becoming rapid at pH 3.5, and inhibition of binding by folate analogues. The gel filtration profile of Triton X-100 solubilized tissue contained two large peaks of 3H-folate labelled protein (> = 130 and 100 kDa) as well as a 25 kDa peak. Only a single band of 70 kDa was seen on SDS-PAGE immunoblotting. The large molecular size forms on gel filtration appear to represent folate receptors having a hydrophobic membrane anchor inserted into Triton X-100 micelles. The folate receptor of female genital tract showed cross-reactivity in ELISA and positive immunostaining with rabbit antibodies against human milk folate binding protein. Variations in the ratio of immunoresponse to total high affinity folic acid binding suggests the presence of multiple isoforms of the receptor in different types of malignant and benign tissues.

  9. 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

  10. 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

  11. Results of chest wall resection for recurrent or locally advanced breast malignancies.

    PubMed

    Veronesi, Giulia; Scanagatta, Paolo; Goldhirsch, Aron; Rietjens, Mario; Colleoni, Marco; Pelosi, Giuseppe; Spaggiari, Lorenzo

    2007-06-01

    Between 1998 and 2003 we observed 15 women who underwent full thickness chest wall resection (FTCWR) followed by plastic reconstruction for locally recurrent or primary breast cancer. Preoperative symptoms were: pain (5 patients), malodorous ulceration (3 patients), presence of tumour mass (4 patients) and thoracic deformity (2 patients). One patient was asymptomatic. Surgery was partial sternectomy with rib resection in 9 patients, rib resection alone in 5, and total sternectomy in one. No perioperative mortality or major morbidity occurred; minor complications occurred in 3 patients (20%). Five of the six surviving patients reported a positive overall outcome in a telephonic interview. Median overall and disease-free survival were 23.4 and 17.5 months, respectively. In conclusion, FTCWR is a safe procedure with low morbidity and mortality that can provide good symptoms palliation in patients with locally advanced breast malignancies, so it should be considered more often by interdisciplinary care providers in those patients who fail to respond to classic multimodality treatment.

  12. Tissue binding pattern of plant lectins in benign and malignant lesions of thyroid.

    PubMed

    Vijayakumar, T; Augustine, J; Mathew, L; Aleykutty, M A; Nair, M B; Remani, P; Nair, M K

    1992-01-01

    N-acetyl D-galactosamine specific lectins were isolated from the seeds of Jack Fruit (Artocarpus integrifolia) and Winged bean (Psophocarpus tetragonolobus) and D-galactose specific lectin was isolated from peanut (Arachis hypogaea). These lectins were conjugated to Horse Radish Peroxidase (HRP) and were used to study the lectin binding properties of benign and malignant lesions of the thyroid. For comparison of the results 10 normal fresh autopsy specimens were included in the study. The Peanut lectin (PNL) and Jack fruit lectin (JFL) conjugates showed positive binding with the cells in different lesions, while Winged Bean Lectin (WBL), despite its having a common inhibitory sugar, showed no binding even after neuraminidase treatment. These lectins revealed difference in the composition of glycoconjugates of benign and malignant thyroid cells. The HRP conjugated JFL and PNL may be of use in distinguishing carcinomatous tissues from benign tissues which makes them potential tools in the differential diagnosis of thyroid lesions.

  13. 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

  14. 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.

  15. 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

  16. Cancer procoagulant: a factor X activator, tumor marker and growth factor from malignant tissue.

    PubMed

    Gordon, S G; Mielicki, W P

    1997-03-01

    Hemostatic abnormalities associated with malignant disease led to the search for and discovery of a proteolytic enzyme that activated factor X in the blood coagulation cascade. It was named cancer procoagulant (CP). CP is a cysteine proteinase that is found in malignant and fetal (human amnion-chorion) tissue; it has not been found in normally differentiated tissue. It is a calcium-dependent, Mn2+ stimulated enzyme that has enhanced activity and inhibition in a reduced environment. This review presents a complete compilation and discussion of the known chemical and enzymatic characteristics of CP as well as many purification and assay procedures. Several unique properties of these procedures are described. Some problems and controversies are highlighted in each of the sections. An immunoassay for CP as a tumor marker and some of its potential applications in the diagnosis and monitoring of cancer are reviewed. Some therapeutic implications of CP are noted in light of the observation that antibodies to CP block the metastatic seeding of lung colonies in vivo and diminish the viability of tumor cells in vitro. Finally, comments about the relationship between tissue factor and CP in the malignant cells are provided.

  17. 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

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

    PubMed

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

    2014-02-15

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

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

    PubMed Central

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

    2014-01-01

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

  20. 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.

  1. 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

  2. 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

  3. Expression of human intestinal trefoil factor in malignant cells and its regulation by oestrogen in breast cancer cells.

    PubMed

    May, F E; Westley, B R

    1997-08-01

    Human intestinal trefoil factor (hITF) is a small cysteine-rich protein expressed in the gastrointestinal (GI) tract. Its sequence is related to that of other trefoil peptides including the pNR-2/pS2 protein, which is regulated by oestrogen in breast cancer. This study was designed to investigate whether hITF is expressed in human carcinoma cells. cDNA was obtained by reverse transcription-polymerase chain reaction (RT-PCR) of gastric mucosal RNA and sequenced, establishing that this mRNA is expressed in the stomach. Expression of hITF was detected in a proportion of cell lines derived from malignancies of the GI tract, in hepatocellular carcinoma cells, and at highest levels in a small cell lung carcinoma cell line. Amongst breast cancer cell lines, it was expressed in all the oestrogen-responsive but in none of the oestrogen-nonresponsive breast cancer cell lines. The possibility that hITF expression in breast cells is controlled by oestradiol was then tested. Oestradiol treatment increased hITF expression between three- and ten-fold in the oestrogen-responsive breast cancer cell lines, demonstrating that, like pNR-2/pS2, hITF is regulated by oestrogen in breast cancer cells. Tamoxifen inhibited the induction of hITF expression by oestradiol but tamoxifen alone was a partial oestrogen agonist for hITF expression. These results show that hITF is expressed, sometimes ectopically, in several human malignancies, which suggests that trefoil peptides may have a more general role in tumourigenesis than hitherto appreciated. That the expression of hITF is regulated by oestrogen in breast cancer cells suggests that hITF expression may provide a novel marker for oestrogen responsiveness in breast cancer.

  4. Molecular classification of breast phyllodes tumors: validation of the histologic grading scheme and insights into malignant progression.

    PubMed

    Ang, Mei Kim; Ooi, Aik Seng; Thike, Aye Aye; Tan, Patrick; Zhang, Zhongfa; Dykema, Karl; Furge, Kyle; Teh, Bin Tean; Tan, Puay Hoon

    2011-09-01

    Phyllodes tumors of the breast are rare fibroepithelial neoplasms with a potential for recurrence. Current histological classification is not always predictive of clinical behavior. The aim of this study was to identify genetic changes associated with the development of borderline and malignant phyllodes tumors in an Asian population, and to assess if genetic data supported the categorization of these tumors into the existing three grades of benign, borderline, and malignant. Expression profiling of 21 phyllodes tumors (6 benign, 10 borderline, 5 malignant) was performed using Affymetrix U133Plus 2.0 GeneChips(®). Gene expression among benign, borderline, and malignant tumors was compared and a 29 gene list was able to classify them according to their histologic grade. Among these 29 genes are those responsible for matrix formation, cell adhesion, epidermis formation, and cell proliferation. Comparative genomic microarray analysis showed that the most common chromosomal alteration associated with borderline and malignant tumors was 1q gain, and an increasing number of chromosomal changes was noted with increasing histological grade. Upregulation of HOXB13 was seen in malignant relative to borderline phyllodes tumors and further investigated by immunohistochemistry in a corresponding set of formalin-fixed, paraffin-embedded tumors. HOXB13 protein overexpression was found to be correlated with stromal hypercellularity and atypia (P = 0.03, P = 0.039, respectively) and may be implicated in the development of malignant phyllodes tumors.

  5. 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.

  6. Tumor-Derived Tissue Factor-Bearing Microparticles are Associated with Venous Thromboembolic Events in Malignancy

    PubMed Central

    Zwicker, Jeffrey I.; Liebman, Howard A.; Neuberg, Donna; Lacroix, Romaric; Bauer, Kenneth A.; Furie, Barbara C.; Furie, Bruce

    2009-01-01

    Purpose Despite the strong association between malignant disease and thromboembolic disorders, the molecular and cellular basis of this relationship remains uncertain. We evaluated the hypothesis that tumor-derived tissue factor-bearing microparticles in plasma contribute to cancer-associated thrombosis. Experimental Design We developed impedance-based flow cytometry to detect, quantitate and size microparticles in platelet-poor plasma. We evaluated the number of tissue factor-bearing microparticles in a cohort of cancer patients of different histologies (N=96) and performed a case control study of 30 cancer patients diagnosed with an acute venous thromboembolic event (VTE) compared to 60 cancer patients of similar age, stage, sex, diagnosis without known VTE as well as 22 patients with an idiopathic VTE. Results Tissue factor-bearing microparticles were detected in patients with advanced malignancy including two thirds of patients with pancreatic carcinoma. Elevated levels of tissue factor-bearing microparticles were associated VTE in cancer patients (adjusted OR 3.72, 95% CI 1.18-11.76, P=0.01). In cancer patients without VTE, a retrospective analysis revealed a one-year cumulative incidence of VTE of 34.8% in patients with tissue factor-bearing microparticles versus 0% those without detectable tissue factor-bearing microparticles (Gray test p-value=0.002). The median number of tissue factor-bearing microparticles in the cancer VTE cohort (7.1 × 104 microparticles/μl) was significantly greater than both the idiopathic VTE and cancer-no VTE groups (P=0.002 and P=0.03, respectively). Pancreatectomy in three patients eliminated or nearly eliminated these microparticles which co-expressed the epithelial tumor antigen, MUC-1. Conclusion We conclude that tumor-derived tissue factor-bearing microparticles are associated with VTE in cancer patients and may be central to the pathogenesis of cancer-associated thrombosis. PMID:19861441

  7. A technique for marking oncological breast tissue specimens

    PubMed Central

    Patel, Jaison; Jenkins, Stephanie

    2016-01-01

    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

  8. 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

  9. 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.

  10. Differentiation and loss of malignant character of spontaneous pulmonary metastases in patient-derived breast cancer models

    PubMed Central

    Bockhorn, Jessica; Prat, Aleix; Chang, Ya-Fang; Liu, Xia; Huang, Simo; Shang, Meng; Nwachukwu, Chika; Gomez-Vega, Maria J.; Harrell, J. Chuck; Olopade, Olufunmilayo I.; Perou, Charles M.; Liu, Huiping

    2014-01-01

    Patient-derived human-in-mouse xenograft models of breast cancer (PDX models) that exhibit spontaneous lung metastases offer a potentially powerful model of cancer metastasis. In this study, we evaluated the malignant character of lung micro-metastases that emerge in such models after orthotopic implantation of human breast tumor cells into the mouse mammary fat pad. Interestingly, relative to the parental primary breast tumors, the lung metastasis (met)-derived mammary tumors exhibited a slower growth rate and a reduced metastatic potential with a more differentiated epithelial status. Epigenetic correlates were determined by gene array analyses. Lung met-derived tumors displayed differential expression of negative regulators of cell proliferation and metabolism and positive regulators of mammary epithelial differentiation. Clinically, this signature correlated with breast tumor subtypes. We identified microRNA-138 as a novel regulator of invasion and epithelial-mesenchymal transition in breast cancer cells, acting by directly targeting the polycomb epigenetic regulator EZH2. Mechanistic investigations showed that GATA3 transcriptionally controlled miR-138 levels in lung metastases. Notably, the miR-138 activity signature served as a novel independent prognostic marker for patient survival beyond traditional pathologic variables, intrinsic subtypes or a proliferation gene signature. Our results highlight the loss of malignant character in some lung micro-metastatic lesions and the epigenetic regulation of this phenotype. PMID:25339353

  11. Detection of soft tissue densities from digital breast tomosynthesis: comparison of conventional and deep learning approaches

    NASA Astrophysics Data System (ADS)

    Fotin, Sergei V.; Yin, Yin; Haldankar, Hrishikesh; Hoffmeister, Jeffrey W.; Periaswamy, Senthil

    2016-03-01

    Computer-aided detection (CAD) has been used in screening mammography for many years and is likely to be utilized for digital breast tomosynthesis (DBT). Higher detection performance is desirable as it may have an impact on radiologist's decisions and clinical outcomes. Recently the algorithms based on deep convolutional architectures have been shown to achieve state of the art performance in object classification and detection. Similarly, we trained a deep convolutional neural network directly on patches sampled from two-dimensional mammography and reconstructed DBT volumes and compared its performance to a conventional CAD algorithm that is based on computation and classification of hand-engineered features. The detection performance was evaluated on the independent test set of 344 DBT reconstructions (GE SenoClaire 3D, iterative reconstruction algorithm) containing 328 suspicious and 115 malignant soft tissue densities including masses and architectural distortions. Detection sensitivity was measured on a region of interest (ROI) basis at the rate of five detection marks per volume. Moving from conventional to deep learning approach resulted in increase of ROI sensitivity from 0:832 +/- 0:040 to 0:893 +/- 0:033 for suspicious ROIs; and from 0:852 +/- 0:065 to 0:930 +/- 0:046 for malignant ROIs. These results indicate the high utility of deep feature learning in the analysis of DBT data and high potential of the method for broader medical image analysis tasks.

  12. 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.

  13. Breast tissue segmentation from x-ray radiographs.

    PubMed

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

    2014-05-21

    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. PMID:24778348

  14. 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.

  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. An imrt technique to increase therapeutic ratio of breast irradiation in patients with early-stage left breast cancer: limiting second malignancies

    SciTech Connect

    Ahmed, Raef S.; Santos, Jennifer F. de los Fiveash, John B.; Keene, Kimberly S.; Popple, Richard A.

    2008-04-01

    The clinical application of intensity modulated radiotherapy (IMRT) for adjuvant treatment of breast cancer has been the subject of increasing study in recent years. IMRT results in improved target coverage, reduced dose inhomogeneity within the breast, and reduced dose to the heart, lungs, and contralateral breast. However, this has been at the cost of larger volumes of low-dose radiation to these structures, thus increasing the theoretic risk for second malignancies. Our goal was to develop an IMRT beam arrangement that did not result in additional low-dose spill to organs at risk while maintaining equal or better target coverage. Five patients with early-stage left-sided breast cancer, who underwent breast conservation surgery and adjuvant radiation therapy, were chosen for this comparative study. The conventional radiation treatment (CRT) plan was comprised of standard wedged tangential fields. An IMRT plan consisting of 6 tangential beams (3 medial and 3 lateral) was generated by using the gantry, collimator, and table angles of the standard plan used for the CRT plan, and moving the table +10 deg. and -10 deg. on each side. The prescription dose for both CRT and IMRT plans was 45 Gy, 1.8 Gy/fraction, prescribed to the isocenter, which was placed near the center of the breast. IMRT plans provided significantly better coverage of the left breast than the CRT plans (p = 0.03). Although the dose heterogeneity was greater with the IMRT plans, the difference was not significant (p = 0.68). The mean volumes of the heart, lung, and right breast were lower in patients planned with IMRT at all dose levels from 5% to 100% dose (5% increments). This difference was significant for volumes receiving 2.25 Gy for the heart (p = 0.003), and volumes receiving 2.25, 4.5, 6.75, 33.75, 36, 38.25, and 42.75 Gy for the lung (p = 0.014, 0.04, 0.044, 0.05, 0.049, 0.045, and 0.05, respectively). Surprisingly, breast IMRT resulted in significantly lower right breast volumes irradiated

  17. Expression of the breast cancer resistance protein and 5-fluorouracil resistance in clinical breast cancer tissue specimens

    PubMed Central

    WANG, MIN; WANG, XIANMING; YUAN, JIANHUI; GUO, LIANGFENG

    2013-01-01

    The breast cancer resistance protein (BCRP) is a recently characterized xenobiotic half-transporter protein that acts as an energy-dependent efflux pump and may be associated with the multidrug-resistant phenotype. The aim of this study was to determine the association between BCRP expression and 5-fluorouracil (5-FU) resistance in clinical breast cancer tissue specimens. The BCRP expression was investigated using quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) by use of the Master SYBR-Green I reagent and immunohistochemistry (IHC) by use of the BXP-21 anti-BCRP monoclonal antibody in clinical breast cancer tissue specimens. Chemosensitivity to 5-FU for BCRP-positive clinical breast cancer tissue specimens was colorimetrically assessed with the cytotoxicity assay through methyl thiazolyl tetrazolium (MTT) reduction. A total of 37 BCRP-positive clinical breast cancer tissue specimens were identified with quantitative RT-PCR and IHC. There was a significant correlation in BCRP expression between the results of quantitative RT-PCR and IHC in the specimens. The fold resistance to 5-FU was 7–12 compared to sensitivity to paclitaxel as determined by the colorimetric assay through MTT reduction in the 37 specimens. Our study results indicated that 5-FU resistance may be mediated by BCRP expression in clinical breast cancer tissue specimens, which may help optimize the design of breast cancer clinical chemotherapy schemes in BCRP-positive specimens. PMID:24649260

  18. Isolation of alpha 1-protease inhibitor from human normal and malignant ovarian tissue.

    PubMed Central

    Bagdasarian, A; Wheeler, J; Stewart, G J; Ahmed, S S; Colman, R W

    1981-01-01

    Proteolytic enzymes are associated with normal and neoplastic tissues. Therefore protease inhibitors might also be involved in the control of cell function. alpha 1-protease antigen and antitryptic activity have been found in normal and neoplastic human ovarian homogenate. The inhibitor has been localized to ovarian stromal cells or tumor cells by immunoperoxidase staining. The protein was purified to apparent homogeneity as judged by alkaline gel and sodium dodecyl sulfate (SDS) gel electrophoresis. Immunochemical studies revealed antigenic similarity of plasma alpha 1-protease inhibitor by double immunodiffusion and similar mobility on immunoelectrophoresis and two-dimensional electroimmunodiffusion. The molecular weight was similar to that described for plasma alpha 1-protease inhibitor: 60,000 by gel filtration and 53,500 by SDS electrophoresis. Furthermore, the phenotypic pattern as determined by acid starch gel electrophoresis and immunoprecipitation was PiMM, which is the predominant genetic variant in normal plasma alpha 1-protease inhibitor. An inhibitor ws isolated and purified from an ovarian carcinoma that exhibited functional, immunochemical, and physical similarity to the normal ovarian alpha 1-protease inhibitor. alpha 1-protease inhibitor from normal and malignant ovaries competitively inhibited bovine pancreatic trypsin at incubation times of 5 min at 30 degrees C. Inhibition constant (Ki) values were calculated at 0.67 and 0.51 inhibitory units, respectively. The alpha 1-protease inhibitor in malignant cells may be a factor in the control of proliferation in this tissue. Since ovulation is in part a proteolytic event, the alpha 1-protease inhibitor in ovarian cells may play a role in the control of this specialized tissue. Persistance of this protein in malignant ovarian tissue may be a vestige of its differentiated origin. Images PMID:6161137

  19. Biomechanical properties of breast tissue, a state-of-the-art review.

    PubMed

    Ramião, Nilza G; Martins, Pedro S; Rynkevic, Rita; Fernandes, António A; Barroso, Maria; Santos, Diana C

    2016-10-01

    This paper reviews the existing literature on the tests used to determine the mechanical properties of women breast tissues (fat, glandular and tumour tissue) as well as the different values of these properties. The knowledge of the mechanical properties of breast tissue is important for cancer detection, study and planning of surgical procedures such as surgical breast reconstruction using pre-surgical methods and improving the interpretation of clinical tests. Based on the data collected from the analysed studies, some important conclusions were achieved: (1) the Young's modulus of breast tissues is highly dependent on the tissue preload compression level, and (2) the results of these studies clearly indicate a wide variation in moduli not only among different types of tissue but also within each type of tissue. These differences were most evident in normal fat and fibroglandular tissues.

  20. Biomechanical properties of breast tissue, a state-of-the-art review.

    PubMed

    Ramião, Nilza G; Martins, Pedro S; Rynkevic, Rita; Fernandes, António A; Barroso, Maria; Santos, Diana C

    2016-10-01

    This paper reviews the existing literature on the tests used to determine the mechanical properties of women breast tissues (fat, glandular and tumour tissue) as well as the different values of these properties. The knowledge of the mechanical properties of breast tissue is important for cancer detection, study and planning of surgical procedures such as surgical breast reconstruction using pre-surgical methods and improving the interpretation of clinical tests. Based on the data collected from the analysed studies, some important conclusions were achieved: (1) the Young's modulus of breast tissues is highly dependent on the tissue preload compression level, and (2) the results of these studies clearly indicate a wide variation in moduli not only among different types of tissue but also within each type of tissue. These differences were most evident in normal fat and fibroglandular tissues. PMID:26862021

  1. 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.

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

    PubMed

    Ritter, Andreas; Friemel, Alexandra; Fornoff, Friderike; Adjan, Mouhib; Solbach, Christine; Yuan, Juping; Louwen, Frank

    2015-10-27

    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.

  3. Tissue binding patterns of lectins in premalignant and malignant lesions of the oral cavity.

    PubMed

    Vijayan, K K; Remani, P; Beevi, V M; Ankathil, R; Vijayakumar, T; Rajendran, R; Augustine, J; Vasudevan, D M

    1987-01-01

    Lectins from the seeds of Jackfruit (Artocarpus integrifolia) and winged bean (Psophocarpus tetragonolobus) were isolated using an immobilized N-acetyl D-galactosamine column and conjugated to type VI horse radish peroxidase. The purified conjugate was used for the study of tissue specificities using diaminobenzidine as the substrate on dewaxed tissue sections of normal, oral leukoplakia, oral submucous fibrosis, verucous carcinoma and squamous cell carcinoma of the oral cavity. In spite of having a common inhibitory sugar, winged bean lectin did not bind to any lectins whereas Jackfruit lectin showed varying degrees of binding towards the above tissues. The difference in the nature and intensity of binding of the Jackfruit lectin suggest the utilizing this lectin in the differential diagnosis of the premalignant and malignant lesions of the oral cavity.

  4. The cellular distribution of Na+/H+ exchanger regulatory factor 1 is determined by the PDZ-I domain and regulates the malignant progression of breast cancer

    PubMed Central

    Du, Guifang; Gu, Yanan; Hao, Chengcheng; Yuan, Zhu; He, Junqi; Jiang, Wen G.; Cheng, Shan

    2016-01-01

    The oncogenic role of ectopic expression of Na+/H+ exchanger regulatory factor 1 (NHERF1) was recently suggested. Here, we show that NHERF1 was upregulated in high grades compared with low grades. Increased NHERF1 expression was correlated with poor prognosis and poor survival. NHERF1 expression was higher in the nucleus of cancer cells than in contiguous non- mammary epithelial cells. A novel mutation, namely NHERF1 Y24S, was identified in human breast cancer tissues and shown to correspond to a conserved residue in the PDZ-I domain of NHERF1. Truncation and mutation of the PDZ-I domain of NHERF1 increased the nuclear distribution of the NHERF1 protein, and this redistribution was associated with the malignant phenotype of breast cancer cells, including growth, migration, and adhesion. The present results suggest a role for NHERF1 in the progression of breast cancer mediated by the nuclear distribution of the NHERF1 protein, as determined by the truncation or key site mutation of the PDZ-I domain. PMID:27097111

  5. Statistical assessment of bi-exponential diffusion weighted imaging signal characteristics induced by intravoxel incoherent motion in malignant breast tumors

    PubMed Central

    Wong, Oi Lei; Lo, Gladys G.; Chan, Helen H. L.; Wong, Ting Ting; Cheung, Polly S. Y.

    2016-01-01

    Background The purpose of this study is to statistically assess whether bi-exponential intravoxel incoherent motion (IVIM) model better characterizes diffusion weighted imaging (DWI) signal of malignant breast tumor than mono-exponential Gaussian diffusion model. Methods 3 T DWI data of 29 malignant breast tumors were retrospectively included. Linear least-square mono-exponential fitting and segmented least-square bi-exponential fitting were used for apparent diffusion coefficient (ADC) and IVIM parameter quantification, respectively. F-test and Akaike Information Criterion (AIC) were used to statistically assess the preference of mono-exponential and bi-exponential model using region-of-interests (ROI)-averaged and voxel-wise analysis. Results For ROI-averaged analysis, 15 tumors were significantly better fitted by bi-exponential function and 14 tumors exhibited mono-exponential behavior. The calculated ADC, D (true diffusion coefficient) and f (pseudo-diffusion fraction) showed no significant differences between mono-exponential and bi-exponential preferable tumors. Voxel-wise analysis revealed that 27 tumors contained more voxels exhibiting mono-exponential DWI decay while only 2 tumors presented more bi-exponential decay voxels. ADC was consistently and significantly larger than D for both ROI-averaged and voxel-wise analysis. Conclusions Although the presence of IVIM effect in malignant breast tumors could be suggested, statistical assessment shows that bi-exponential fitting does not necessarily better represent the DWI signal decay in breast cancer under clinically typical acquisition protocol and signal-to-noise ratio (SNR). Our study indicates the importance to statistically examine the breast cancer DWI signal characteristics in practice. PMID:27709078

  6. Volume and tissue composition preserving deformation of breast CT images to simulate breast compression in mammographic imaging

    NASA Astrophysics Data System (ADS)

    Han, Tao; Chen, Lingyun; Lai, Chao-Jen; Liu, Xinming; Shen, Youtao; Zhong, Yuncheng; Ge, Shuaiping; Yi, Ying; Wang, Tianpeng; Shaw, Chris C.

    2009-02-01

    Images of mastectomy breast specimens have been acquired with a bench top experimental Cone beam CT (CBCT) system. The resulting images have been segmented to model an uncompressed breast for simulation of various CBCT techniques. To further simulate conventional or tomosynthesis mammographic imaging for comparison with the CBCT technique, a deformation technique was developed to convert the CT data for an uncompressed breast to a compressed breast without altering the breast volume or regional breast density. With this technique, 3D breast deformation is separated into two 2D deformations in coronal and axial views. To preserve the total breast volume and regional tissue composition, each 2D deformation step was achieved by altering the square pixels into rectangular ones with the pixel areas unchanged and resampling with the original square pixels using bilinear interpolation. The compression was modeled by first stretching the breast in the superior-inferior direction in the coronal view. The image data were first deformed by distorting the voxels with a uniform distortion ratio. These deformed data were then deformed again using distortion ratios varying with the breast thickness and re-sampled. The deformation procedures were applied in the axial view to stretch the breast in the chest wall to nipple direction while shrinking it in the mediolateral to lateral direction re-sampled and converted into data for uniform cubic voxels. Threshold segmentation was applied to the final deformed image data to obtain the 3D compressed breast model. Our results show that the original segmented CBCT image data were successfully converted into those for a compressed breast with the same volume and regional density preserved. Using this compressed breast model, conventional and tomosynthesis mammograms were simulated for comparison with CBCT.

  7. 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

  8. 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.

  9. 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.

  10. 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

    2016-02-22

    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.

  11. 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

  12. [Toxic effects of cisplatin in the treatment of malignant bone and soft tissue tumors].

    PubMed

    Umeda, T; Takada, N; Hodaka, E; Endoh, F; Ishii, T

    1986-05-01

    A total of 31 patients with malignant bone and soft tissue tumors were evaluated for toxic effects after receiving cisplatin (104 courses) at doses of 2.0-3.0 mg/kg with aggressive hydration. Nausea was common and in 86% of cisplatin courses severe vomiting was observed. Nephrotoxicity was observed in less than 10% of all courses but ototoxicity, especially tinnitis, developed in 5 of 6 patients whose total doses of cisplatin were over 500mg, and one of them showed hearing disorder in the upper frequency above 5,000 Hz. There were no other toxic effects such as severe myelosuppression, allergic reaction or peripheral neuropathy. PMID:3707148

  13. Diagnostic dilemma involving a mass in the parapharyngeal space: A metastatic breast carcinoma masquerading as a malignant salivary gland tumor.

    PubMed

    Murhekar, Kanchan; Majhi, Urmila; Krishnamurthy, Arvind; Ramshankar, Vijayalakshmi

    2015-01-01

    Parapharyngeal space (PPS) tumors are rare and account for about 0.5% of all head and neck neoplasms. Most PPS tumors are benign (up to 80%) while the remaining 20% are malignant. These tumors are either primaries; most commonly arising from salivary glands or metastatic tumors or due to direct extension of tumors from the adjacent sites. Distant metastasis from breast cancers more commonly involves the lungs, bones, brain and liver. Metastasis to the PPS from a primary breast carcinoma is rare, with only one case reported in literature. We, to the best of our knowledge report the second case of a carcinoma breast metastasizing to the PPS and further discuss the diagnostic and therapeutic challenges involved in its management. A fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography scan apart from explicitly defining the extent of the PPS tumor, majorly influenced the therapeutic decision making process by ruling out other sites of metastasis.

  14. 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

  15. Early tissue reaction to textured breast implant surfaces.

    PubMed

    Brohim, R M; Foresman, P A; Hildebrandt, P K; Rodeheaver, G T

    1992-04-01

    Capsular contracture around breast implants with smooth surfaces continues to be an unpredictable complication. Some surgeons believe that silicone implants covered with porous polyurethane foam have a lowered potential to contract. These textured implants are not as biocompatible as silicone. Recently, silicone implants with textured surfaces have been introduced with the hope that the incidence of unacceptable implant contracture will be reduced. Using a rat implant model, the tissue reaction to textured implant surfaces was assessed. The implant surfaces evaluated were Silastic II, Siltex, MISTI, Biocell, Silastic MSI, and Même. Disks of each implant material were implanted under the dorsal skin of rats for a period of 28 days. Each implant with its surrounding tissue was excised, processed for histological analysis, and assessed for the tissue's response to the implant with particular emphasis on the formation of a continuous collagen capsule. The results indicated that the magnitude of surface texturing influenced the development of a complete capsule. Implant surfaces with a texture of less than 150 microns in height or depth (Silastic II, Siltex, and MISTI) resulted in the formation of complete capsules. An implant (Biocell) with irregular texturing (200-350 microns) produced an organized capsule over most of its surface with localized interruptions of the capsule at the sites of its deepest cavities. Implant surfaces with texturing that exceeded 350 microns in height or depth (Silastic MSI and Même) resulted in inhibition of the formation of a continuous capsule during this 28-day study.

  16. 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.

  17. Classification and immunohistochemical scoring of breast tissue microarray spots.

    PubMed

    Amaral, Telmo; McKenna, Stephen J; Robertson, Katherine; Thompson, Alastair

    2013-10-01

    Tissue microarrays (TMAs) facilitate the survey of very large numbers of tumors. However, the manual assessment of stained TMA sections constitutes a bottleneck in the pathologist's work flow. This paper presents a computational pipeline for automatically classifying and scoring breast cancer TMA spots that have been subjected to nuclear immunostaining. Spots are classified based on a bag of visual words approach. Immunohistochemical scoring is performed by computing spot features reflecting the proportion of epithelial nuclei that are stained and the strength of that staining. These are then mapped onto an ordinal scale used by pathologists. Multilayer perceptron classifiers are compared with latent topic models and support vector machines for spot classification, and with Gaussian process ordinal regression and linear models for scoring. Intraobserver variation is also reported. The use of posterior entropy to identify uncertain cases is demonstrated. Evaluation is performed using TMA images stained for progesterone receptor.

  18. 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

  19. 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.

  20. 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

  1. Breast Cancer classification using extracted parameters from a terahertz dielectric model of human breast tissue.

    PubMed

    Truong, Bao C Q; Tuan, H D; Fitzgerald, Anthony J; Wallace, Vincent P; Tuan Nghia Nguyen; Nguyen, H T

    2015-08-01

    Our previous study proposed a dielectric model for human breast tissue and provided initial analysis of classification potential of the eight model parameters and their multiparameter combinations with the support vector machine (SVM). A combination of three model parameters could achieve a leave-one-out cross validation accuracy of 93.2%. However, the SVM approach fails to exploit the combinations of more than three model parameters for classification improvement. Thus, the Bayesian neural network (BNN) method is employed to overcome this problem based on its advantages of handling our small data and high complexity of the multiparamter combinations. The BNN successfully classifies the data using the combinations of four model parameters with an accuracy, estimated by leave-one-out cross validation, of 97.3%. Overall performance assessed by leaveone-out and repeated random-subsampling cross validations for all examined combinations is also remarkably improved by BNN. The results indicate the advance of BNN as compared to SVM in utilising the model parameters for detecting tumour from normal breast tissue. PMID:26736874

  2. Minireview: The Androgen Receptor in Breast Tissues: Growth Inhibitor, Tumor Suppressor, Oncogene?

    PubMed Central

    Hickey, T. E.; Robinson, J. L. L.; Carroll, J. S.

    2012-01-01

    Androgen receptor (AR) signaling exerts an antiestrogenic, growth-inhibitory influence in normal breast tissue, and this role may be sustained in estrogen receptor α (ERα)-positive luminal breast cancers. Conversely, AR signaling may promote growth of a subset of ERα-negative, AR-positive breast cancers with a molecular apocrine phenotype. Understanding the molecular mechanisms whereby androgens can elicit distinct gene expression programs and opposing proliferative responses in these two breast cancer phenotypes is critical to the development of new therapeutic strategies to target the AR in breast cancer. PMID:22745190

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

    PubMed

    Charles, Amelia K; Darbre, Philippa D

    2013-05-01

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

  4. Of mice and women: a comparative tissue biology perspective of breast stem cells and differentiation.

    PubMed

    Dontu, Gabriela; Ince, Tan A

    2015-06-01

    Tissue based research requires a background in human and veterinary pathology, developmental biology, anatomy, as well as molecular and cellular biology. This type of comparative tissue biology (CTB) expertise is necessary to tackle some of the conceptual challenges in human breast stem cell research. It is our opinion that the scarcity of CTB expertise contributed to some erroneous interpretations in tissue based research, some of which are reviewed here in the context of breast stem cells. In this article we examine the dissimilarities between mouse and human mammary tissue and suggest how these may impact stem cell studies. In addition, we consider the differences between breast ducts vs. lobules and clarify how these affect the interpretation of results in stem cell research. Lastly, we introduce a new elaboration of normal epithelial cell types in human breast and discuss how this provides a clinically useful basis for breast cancer classification.

  5. Near-infrared spectroscopy as a diagnostic tool for distinguishing between normal and malignant colorectal tissues.

    PubMed

    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

  6. Altered expression of Lewis blood group and related antigens in fetal, normal adult and malignant tissues of the uterine endometrium.

    PubMed

    Inoue, M; Nakayama, M; Tanizawa, O

    1990-01-01

    The expression of the Lewis blood group and its related antigens in fetal, normal adult and malignant tissues of the uterine endometrium was examined immunohistochemically using a panel of mouse monoclonal antibodies with specificities for Lewis-a (La), Sialyl Lewis-a (SLa), Lewis-b (Lb), Lewis-X (LX), Sialyl Lewis-X (SLX) and Lewis-Y (LY) antigens. La, SLa and SLX having one fucose residue were detected in a small number of fetal tissues, while Lb and LY having two fucose residues were found in most cases. In the adult endometrium, expression of Lb and LY was considerably lower than those in fetal tissues, although expression of La and SLa was not different between these two tissues. Expression of LX and SLX was pronounced in adult when compared with fetal tissues. Malignant endometrial glands expressed La, SLa, Lb and LY, extensively, while LX and SLX were expressed less than in normal tissues. Lb and LY can thus be considered oncofetal antigens, extensively expressed in fetal and malignant tissues but not in normal adult tissues. Expression of Lb and LY was greater than that of La and SLA in carcinoma; an increase in the activity of fucose transferase might be associated with malignant transformation in the uterine endometrium.

  7. 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

  8. 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).

  9. 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.

  10. Assessment of Breast Specimens With or Without Calcifications in Diagnosing Malignant and Atypia for Mammographic Breast Microcalcifications Without Mass: A STARD-Compliant Diagnostic Accuracy Article.

    PubMed

    Cheung, Yun-Chung; Juan, Yu-Hsiang; Ueng, Shir-Hwa; Lo, Yung-Feng; Huang, Pei-Chin; Lin, Yu-Ching; Chen, Shin-Cheh

    2015-10-01

    Presence of microcalcifications within the specimens frequently signifies a successful attempt of stereotactic vacuum-assisted breast biopsy (VABB) in obtaining a pathologic diagnosis of the breast microcalcifications. In this study, the authors aimed to assess and compare the accuracy and consistency of calcified or noncalcified specimens obtained from same sites of sampling on isolated microcalcifications without mass in diagnosing high-risk and malignant lesions. To the best of our knowledge, an individual case-based prospective comparison has not been reported.With the approval from institutional review board of our hospital (Chang Gung Memorial Hospital), the authors retrospectively reviewed all clinical cases of stereotactic VABBs on isolated breast microcalcifications without mass from our database. The authors included those having either surgery performed or had clinical follow-up of at least 3 years for analysis. All the obtained specimens with or without calcification were identified using specimen radiographs and separately submitted for pathologic evaluation. The concordance of diagnosis was assessed for both atypia and malignant lesions.A total of 390 stereotactic VABB procedures (1206 calcified and 1456 noncalcified specimens) were collected and reviewed. The consistent rates between calcified and noncalcified specimens were low for atypia and malignant microcalcifications (44.44% in flat epithelial atypia, 46.51% in atypical ductal hyperplasia, 55.73% in ductal carcinoma in situ, and 71.42% in invasive ductal carcinoma). The discordance in VABB diagnoses indicated that 41.33% of malignant lesions would be misdiagnosed by noncalcified specimens. Furthermore, calcified specimens showed higher diagnostic accuracy of breast cancer as compared with the noncalcified specimens (91.54 % versus 69.49%, respectively). The evaluation of both noncalcified specimens and calcified specimens did not show improvement of diagnostic accuracy as compared with

  11. 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.

  12. 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.

  13. 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

  14. 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Expression of SATB1 protein in the ductal breast carcinoma tissue microarrays - preliminary study.

    PubMed

    Kobierzycki, Christopher; Wojnar, Andrzej; Dziegiel, Piotr

    2013-01-01

    Special AT-rich sequence-binding protein 1 (SATB1) is a nuclear matrix protein which interacts with specific regions of DNA, ensuring its proper organization and function in the cell. The expression of SATB1 was primarily found in thymocytes, but its increased levels were observed in various types of cancers. However, the knowledge of the function and application possibilities of this protein is still limited. The aim of this study was to investigate the expression of SATB1 protein using immunohistochemistry and tissue microarray (TMA) technique and determine its possible relationship with the proliferative marker Ki-67, estrogen a (ER) and progesterone (PR) receptors as well as grade of histological malignancy (G). The study was performed on material of 48 archival invasive ductal breast cancers (IDC). The TMAs were prepared with the use of 0.6 mm diameter punches. Immunohistochemical reactions were carried out using antibodies against Ki-67, ER, PR and SATB1 proteins. The intensity of the nuclear reaction was evaluated using a light microscope and computer-assisted image analysis. Expression of Ki-67 and SATB1 protein was observed in 89.58% and 31.25% of cancer cases, respectively. 62.5% of tumors were classified as ER-positive, and 47.92% as PR-positive. Statistical analysis showed a moderate positive correlation between Ki-67 and SATB1 expression (r = 0.291, p = 0.045 independently on the receptor status, and r = 0.392, p = 0.032 in ER-negative tumors). The expression of the Ki-67 antigen increased with higher grade of histological malignancy (G). The results suggest that SATB1 protein may play an indirect role in the cell proliferation and should be evaluated in relation to the other markers. Further studies concerning determination of its role in cancer progression and metastasis, in terms of application as therapeutic target and prognostic marker, are recommended.

  2. 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

  3. Anisotropic Properties of Breast Tissue Measured by Acoustic Radiation Force Impulse Quantification.

    PubMed

    Zhou, JianQiao; Yang, ZhiFang; Zhan, WeiWei; Dong, YiJie; Zhou, Chun

    2016-10-01

    The goal of our study was to investigate the anisotropy of normal breast glandular and fatty tissue with acoustic radiation force impulse (ARFI) quantification. A total of 137 breasts in 137 women were enrolled. These breasts were divided into the duct-apparent group and the duct-inapparent group, divided into the ligament-apparent group and the ligament-inapparent group. Shear wave velocity (SWV) in the radial (SWV(r)) and anti-radial (SWV(a-r)) directions was measured. The elastic anisotropy of glandular tissue and fatty tissue was evaluated as the ratio between SWV(r) and SWV(a-r). The SWV ratio was 1.30 ± 0.45 for glandular tissue and 1.27 ± 0.53 for fatty tissue in the total group. In glandular tissue, the SWV ratio of the duct-apparent group was higher than that of the duct-inapparent group (p = 0.011). In both glandular and fatty tissue, the SWV ratio was higher in the ligament-apparent group than in the ligament-inapparent group (p < 0.05 for both). SWV(r) was higher than SWV(a-r) in both glandular tissue and fatty tissue in all groups (p < 0.05 for all) except in breast fatty tissue in the ligament-inapparent group (p = 0.913). It is concluded that both breast glandular tissue and fatty tissue exhibited anisotropy of elastic behavior. To improve the diagnostic power of elastography in breast lesions, the elastic anisotropy of glandular tissue and fatty tissue should be taken into account in calculating strain ratio or elasticity ratio.

  4. Anisotropic Properties of Breast Tissue Measured by Acoustic Radiation Force Impulse Quantification.

    PubMed

    Zhou, JianQiao; Yang, ZhiFang; Zhan, WeiWei; Dong, YiJie; Zhou, Chun

    2016-10-01

    The goal of our study was to investigate the anisotropy of normal breast glandular and fatty tissue with acoustic radiation force impulse (ARFI) quantification. A total of 137 breasts in 137 women were enrolled. These breasts were divided into the duct-apparent group and the duct-inapparent group, divided into the ligament-apparent group and the ligament-inapparent group. Shear wave velocity (SWV) in the radial (SWV(r)) and anti-radial (SWV(a-r)) directions was measured. The elastic anisotropy of glandular tissue and fatty tissue was evaluated as the ratio between SWV(r) and SWV(a-r). The SWV ratio was 1.30 ± 0.45 for glandular tissue and 1.27 ± 0.53 for fatty tissue in the total group. In glandular tissue, the SWV ratio of the duct-apparent group was higher than that of the duct-inapparent group (p = 0.011). In both glandular and fatty tissue, the SWV ratio was higher in the ligament-apparent group than in the ligament-inapparent group (p < 0.05 for both). SWV(r) was higher than SWV(a-r) in both glandular tissue and fatty tissue in all groups (p < 0.05 for all) except in breast fatty tissue in the ligament-inapparent group (p = 0.913). It is concluded that both breast glandular tissue and fatty tissue exhibited anisotropy of elastic behavior. To improve the diagnostic power of elastography in breast lesions, the elastic anisotropy of glandular tissue and fatty tissue should be taken into account in calculating strain ratio or elasticity ratio. PMID:27471118

  5. 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

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

    PubMed Central

    Mioton, Lauren M; Jordan, Sumanas W

    2015-01-01

    Background Breast projection is a critical element of breast reconstruction aesthetics, but little has been published regarding breast projection as the firm expander is changed to a softer implant. Quantitative data representing this loss in projection may enhance patient education and improve our management of patient expectations. Methods Female patients who were undergoing immediate tissue-expander breast reconstruction with the senior author were enrolled in this prospective study. Three-dimensional camera software was used for all patient photographs and data analysis. Projection was calculated as the distance between the chest wall and the point of maximal projection of the breast form. Values were calculated for final tissue expander expansion and at varying intervals 3, 6, and 12 months after implant placement. Results Fourteen breasts from 12 patients were included in the final analysis. Twelve of the 14 breasts had a loss of projection at three months following the implant placement or beyond. The percentage of projection lost in these 12 breasts ranged from 6.30% to 43.4%, with an average loss of projection of 21.05%. Conclusions This study is the first prospective quantitative analysis of temporal changes in breast projection after expander-implant reconstruction. By prospectively capturing projection data with three-dimensional photographic software, we reveal a loss of projection in this population by three months post-implant exchange. These findings will not only aid in managing patient expectations, but our methodology provides a foundation for future objective studies of the breast form. PMID:26015886

  7. Reliability of Breast Ultrasound BI-RADS Final Assessment in Mammographically Negative Patients with Nipple Discharge and Radiologic Predictors of Malignancy

    PubMed Central

    Park, Chae Jung; Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun

    2016-01-01

    Purpose The purpose of this study was to retrospectively investigate the reliability of breast ultrasound (US) Breast Imaging Reporting and Data System (BI-RADS) final assessment in mammographically negative patients with pathologic nipple discharge, and to determine the clinical and ultrasonographic variables associated with malignancy in this group of patients. Methods A total of 65 patients with 67 mammographically negative breast lesions that were pathologically confirmed through US-guided biopsy were included. Results Of the 53 BI-RADS category 4 and 5 lesions, eight (15.1%) were malignant (six ductal carcinomas in situ, one invasive ductal carcinoma, and one solid papillary carcinoma). There was no malignancy among the remaining 14 category 3 lesions. Malignant lesions more frequently displayed a round or irregular shape (75.0%, 6/8; p=0.030) and nonparallel orientation (33.3%, 4/12; p=0.029) compared to the benign lesions. The increase in the BI-RADS category corresponded with a rise in the malignancy rate (p=0.004). Conclusion The BI-RADS lexicon and final assessment of breast US reliably detect and characterize malignancy in mammographically negative patients with pathologic nipple discharge. PMID:27721881

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. Malignant mixed tumour arising from minor salivary gland tissue of the right parapharyngeal space with metastasis to the scalp.

    PubMed

    Tan, P H; Chew, C T; Cheah, E S

    1992-05-01

    A case of malignant mixed tumour arising from minor salivary gland tissue in the right parapharyngeal space with metastasis to the scalp is described. Both the clinical presentation and the histological picture were unusual. The simultaneous discovery of the primary parapharyngeal tumour and its scalp metastasis, the relatively young age of the patient (43 years-old), the origin of the tumour in minor salivary gland tissue, and the presence of a benign stromal component in the metastasis are features not commonly described in the three entities covered by the term "malignant mixed tumour". We believe this case represents a distinct variant, whose behaviour and progression have not been previously well documented.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    MedlinePlus

    ... medlineplus.gov/news/fullstory_160302.html Sugary, High-Fat Western Diet Tied to Denser Breast Tissue Previous ... found in a Western-style diet, especially high-fat dairy products (whole milk, high-fat cheeses and ...

  18. Second malignancies following conventional or combined 252Cf neutron brachytherapy with external beam radiotherapy for breast cancer

    PubMed Central

    Valuckas, Konstantinas Povilas; Atkocius, Vydmantas; Kuzmickiene, Irena; Aleknavicius, Eduardas; Liukpetryte, Sarune; Ostapenko, Valerijus

    2013-01-01

    We retrospectively evaluated the risk of second malignancies among 832 patients with inner or central breast cancer treated with conventional external beam schedule (CRT group), or neutron brachytherapy using Californium-252 (252Cf) sources and hypofractionated external beam radiotherapy (HRTC group), between 1987 and 1996 at the Institute of Oncology, Vilnius University. Patients were observed until the occurrences of death or development of a second malignancy, or until 31 December 2009, whichever was earlier. Median follow-up time was 10.4 years (range, 1.2–24.1 years). Risk of second primary cancers was quantified using standardized incidence ratios (SIRs). Cox proportional hazards regression models were used to estimate hazard ratios (HRs). There was a significant increase in the risk of second primary cancers compared with the general population (SIR 1.3, 95% CI 1.1–1.5). The observed number of second primary cancers was also higher than expected for breast (SIR 1.8, 95% CI 1.3–2.4) and lung cancer (SIR 3.8, 95% CI 2.0–6.7). For second breast cancer, no raised relative risk was observed during the period ≥10 or more years after radiotherapy. Compared with the CRT group, HRTC patients had a not statistically significant higher risk of breast cancer. Increased relative risks were observed specifically for age at initial diagnosis of <50 years (HR 2.9, 95% CI 1.6–5.2) and for obesity (HR 2.8, 95% CI 1.1–7.2). PMID:23397075

  19. 3-D visualization and non-linear tissue classification of breast tumors using ultrasound elastography in vivo.

    PubMed

    Sayed, Ahmed; Layne, Ginger; Abraham, Jame; Mukdadi, Osama M

    2014-07-01

    The goal of the study described here was to introduce new methods for the classification and visualization of human breast tumors using 3-D ultrasound elastography. A tumor's type, shape and size are key features that can help the physician to decide the sort and extent of necessary treatment. In this work, tumor type, being either benign or malignant, was classified non-invasively for nine volunteer patients. The classification was based on estimating four parameters that reflect the tumor's non-linear biomechanical behavior, under multi-compression levels. Tumor prognosis using non-linear elastography was confirmed with biopsy as a gold standard. Three tissue classification parameters were found to be statistically significant with a p-value < 0.05, whereas the fourth non-linear parameter was highly significant, having a p-value < 0.001. Furthermore, each breast tumor's shape and size were estimated in vivo using 3-D elastography, and were enhanced using interactive segmentation. Segmentation with level sets was used to isolate the stiff tumor from the surrounding soft tissue. Segmentation also provided a reliable means to estimate tumors volumes. Four volumetric strains were investigated: the traditional normal axial strain, the first principal strain, von Mises strain and maximum shear strain. It was noted that these strains can provide varying degrees of boundary enhancement to the stiff tumor in the constructed elastograms. The enhanced boundary improved the performance of the segmentation process. In summary, the proposed methods can be employed as a 3-D non-invasive tool for characterization of breast tumors, and may provide early prognosis with minimal pain, as well as diminish the risk of late-stage breast cancer.

  20. 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.

  1. A novel MR-guided interventional device for 3D circumferential access to breast tissue

    PubMed Central

    Smith, Matthew; Zhai, Xu; Harter, Ray; Sisney, Gale; Elezaby, Mai; Fain, Sean

    2008-01-01

    MRI is rapidly growing as a tool for image-guided procedures in the breast such as needle localizations, biopsy, and cryotherapy. The ability of MRI to resolve small (<1 cm) lesions allows earlier detection and diagnosis than with ultrasound. Most MR-guidance methods perform a two-dimensional compression of the breast that distorts tissue anatomy and limits medial access. This work presents a system for localizing breast lesions with 360° access to breast tissue. A novel system has been developed to perform breast lesion localization using MR guidance that uses a 3D radial coordinate system with four degrees of freedom. The device is combined with a novel breast RF coil for improved signal to noise and rotates 360° around the breast to allow medial, lateral, superior, and inferior access minimizing insertion depth to the target. Coil performance was evaluated using a human volunteer by comparing signal to noise from both the developed breast RF coil and a commercial seven-channel breast coil. The system was tested with a breast-shaped gel phantom containing randomly distributed MR-visible targets. MR-compatible localization needles were used to demonstrate the accuracy and feasibility of the concept for breast biopsy. Localization results were classified based on the relationship between the final needle tip position and the lesion. A 3D bladder concept was also tested using animal tissue to evaluate the device’s ability to immobilize deformable breast tissue during a needle insertion. The RF breast coil provided signal to noise values comparable to a seven-channel breast coil. The needle tip was in contact with the targeted lesion in 89% (25∕28) of all the trials and 100% (6∕6) of the trials with targeted lesions >6 mm. Target lesions were 3–4 mm in diameter for 47% (13∕28), 5–6 mm in diameter for 32% (9∕28), and over 6 mm in diameter for 21% (6∕28) of the trials, respectively. The 3D bladder concept was shown to immobilize a deformable animal

  2. 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

  3. 25-Hydroxyvitamin D3 1alpha-hydroxylase splice variants in benign and malignant ovarian cell lines and tissue.

    PubMed

    Fischer, Dorothea; Thomé, Marlene; Becker, Steffi; Cordes, Tim; Diedrich, Klaus; Friedrich, Michael; Thill, Marc

    2009-09-01

    Calcitriol is judged to have a positive effect on control of the immune system, cell growth and differentiation and therefore, the prevention of cancer genesis. The aim of this study was to detect any possible differences in the 25-hydroxyvitamin D-1alpha-hydroxylase (1alphaOHase)-expression between benign and malignant ovarian tissue and cell lines. The analysis was conducted quantitatively, by means of nested "touchdown" PCR and Western blot, and qualitatively, with the use of real-time PCR and Western blot. The gene structure was sequenced. Compared to the benign cell line, the malignant cell lines showed a significantly higher expression of 1alphaOHase at the RNA level. A statistically lower expression of the 1alphaOHase protein was found in the malignant tissue. In the malignant cell lines and tissues, divergent bands were detected, which led to various splice variants on sequencing. Their increased expression in malignancy is possibly bound to the reduction of enzyme activity, which may lead to the genesis of ovarian cancer. In the future, preventive and therapeutic activities may result from these findings. PMID:19667158

  4. 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

  5. 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.

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

    PubMed Central

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

    2012-01-01

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

  7. Dielectric characterization of healthy and malignant colon tissues in the 0.5–18 GHz frequency band

    NASA Astrophysics Data System (ADS)

    Fornes-Leal, A.; Garcia-Pardo, C.; Frasson, M.; Pons Beltrán, V.; Cardona, N.

    2016-10-01

    Several reports over the last few decades have shown that the dielectric properties of healthy and malignant tissues of the same body organ usually show different values. However, no intensive dielectric studies of human colon tissue have been performed, despite colon cancer’s being one of the most common types of cancer in the world. In order to provide information regarding this matter, a dielectric characterization of healthy and malignant colon tissues is presented. Measurements are performed on ex vivo surgery samples obtained from 20 patients, using an open-ended coaxial probe in the 0.5–18 GHz frequency band. Results show that the dielectric constant of colon cancerous tissue is 8.8% higher than that of healthy tissues (p  =  0.002). Besides, conductivity is about 10.6% higher, but in this case measurements do not have statistical significance (p  =  0.038). Performing an analysis per patient, the differences in dielectric constant between healthy and malignant tissues appear systematically. Particularized results for specific frequencies (500 MHz, 900 MHz, 2.45 GHz, 5 GHz, 8.5 GHz and 15 GHz) are also reported. The findings have potential application in early-stage cancer detection and diagnosis, and can be useful in developing new tools for hyperthermia treatments as well as creating electromagnetic models of healthy and cancerous tissues.

  8. Average Dielectric Property Analysis of Complex Breast Tissue with Microwave Transmission Measurements

    PubMed Central

    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

  9. 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.

  10. 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

  11. 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

  12. 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

  13. The anti-apoptotic protein lifeguard is expressed in breast cancer cells and tissues.

    PubMed

    Bucan, Vesna; Reimers, Kerstin; Choi, Claudia Yu; Eddy, Mau-Thek; Vogt, Peter M

    2010-06-01

    Lifeguard (LFG) is an anti-apoptotic protein that inhibits Fas-mediated death in tumour cells. However, the molecular function of human LFG in the carcinogenesis of human breast cells is uncertain. We studied the expression and function of endogenous LFG in four breast cancer cell lines (MCF-7, MDA-MB-231, T-47D and HS 578T), a human breast epithelial cell line (HS 578Bst), and in healthy and cancerous breast tissues. Molecular (Western blot and RT-PCR) and immunohistochemical techniques were used to investigate the LFG expression. To investigate the breast cancer cell proliferation in the presence of Fas, we performed fluorescent cell viability assays. The possible association of Fas with LFG was analyzed by immunofluorescence microscopy. In this paper, we provide convincing evidence that LFG is overexpressed in several human breast cancer cell lines. More importantly, we found that the LFG expression correlates with high tumour grades in primary breast tumours. Finally, we demonstrated that Fas sensitivity is reduced in breast cancer cell lines expressing LFG. Our results indicated that LFG is strongly expressed in breast cancer epithelial cells. Moreover, the overexpression of LFG correlated with tumour grade and reduced Fas sensitivity. Our findings support the idea that LFG may have a role in the downregulation of apoptosis in breast cancer cells.

  14. Breast Cancer

    MedlinePlus

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

  15. 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

  16. [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

  17. 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.

  18. UV-fluorescence spectroscopic technique in the diagnosis of breast, ovarian, uterus, and cervix cancer

    NASA Astrophysics Data System (ADS)

    Das, Bidyut B.; Glassman, Wenling S.; Alfano, Robert R.; Cleary, Joseph; Prudente, R.; Celmer, Edward J.; Lubicz, Stephanie

    1991-06-01

    Malignant breast tumors can be separated from benign and normal tissues using uv-fluorescence spectroscopic technique. Using the same method one can also distinguish cancerous tissues from noncancerous ones in case of cervix, uterus and ovary.

  19. 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

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

    PubMed

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

    2015-07-01

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

  1. Risk factors for lymphatic metastasis of malignant bone and soft-tissue tumors: a retrospective cohort study of 242 patients.

    PubMed

    Yanagawa, Takashi; Saito, Kenichi; Takagishi, Kenji

    2014-12-01

    Metastasis to the lymph nodes is relatively rare in malignant bone and soft-tissue tumors, and its risk factors remains unknown, except for tumors of the lymphogenous histotype, including rhabdomyosarcoma, epithelioid sarcoma, and clear cell sarcoma. The purpose of this study was to identify the risk factors for lymph node metastasis of malignant bone and soft-tissue tumors. We retrospectively reviewed 242 patients with malignant bone and soft-tissue tumors. The predictors of interest for the risk of lymph node metastasis included age, sex, histopathological diagnosis, location(s) of the primary tumor(s), local recurrence, residual tumor(s), and the size of the primary tumors. To identify the risk factors for lymph node metastasis, Cox regression analyses were performed. Among the 242 patients with malignant bone and soft-tissue tumors in the current study, 60, 29, and 28 were detected to have lung, lymph node, and bone metastases, respectively. In the univariate analyses, the lymphogenous histotype and a primary tumor invading the subcutis were the risk factors for lymph node metastasis. In the multivariate analysis, the lymphogenous histotype (P < 0.01) and a primary tumor in the subcutis (P < 0.01) remained significantly associated with a higher risk of lymph node metastasis with 5.15 and 3.48 of hazard ratios, respectively. Lymph node metastasis was detected in malignant bone and soft-tissue tumors more frequently than that has been previously reported, and the risk factors for lymph node metastasis were the lymphogenous histotype and primary tumors invading the subcutis.

  2. 5α-Reductase Type 3 Expression in Human Benign and Malignant Tissues: A Comparative Analysis During Prostate Cancer Progression

    PubMed Central

    Godoy, Alejandro; Kawinski, Elzbieta; Li, Yun; Oka, Daizo; Alexiev, Borislav; Azzouni, Faris; Titus, Mark A.; Mohler, James L.

    2015-01-01

    BACKGROUND A third isozyme of human 5α-steroid reductase, 5α-reductase-3, was identified in prostate tissue at the mRNA level. However, the levels of 5α-reductase-3 protein expression and its cellular localization in human tissues remain unknown. METHODS A specific monoclonal antibody was developed, validated, and used to characterize for the first time the expression of 5α-reductase-3 protein in 18 benign and 26 malignant human tissue types using immunostaining analyses. RESULTS AND CONCLUSIONS In benign tissues, 5α-reductase-3 immunostaining was high in conventional androgen-regulated human tissues, such as skeletal muscle and prostate. However, high levels of expression also were observed in non-conventional androgen-regulated tissues, which suggest either multiples target tissues for androgens or different functions of 5α-reductase-3 among human tissues. In malignant tissues, 5α-reductase-3 immunostaining was ubiquitous but particularly over-expressed in some cancers compared to their benign counterparts, which suggests a potential role for 5α-reductase-3 as a biomarker of malignancy. In benign prostate, 5α-reductase-3 immunostaining was localized to basal epithelial cells, with no immunostaining observed in secretory/luminal epithelial cells. In high-grade prostatic intraepithelial neoplasia (HGPIN), 5α-reductase-3 immunostaining was localized in both basal epithelial cells and neoplastic epithelial cells characteristic of HGPIN. In androgen-stimulated and castration-recurrent prostate cancer (CaP), 5α-reductase-3 immunostaining was present in most epithelial cells and at similar levels, and at levels higher than observed in benign prostate. Analyses of expression and functionality of 5α-reductase-3 in human tissues may prove useful for development of treatment for benign prostatic enlargement and prevention and treatment of CaP. PMID:21557268

  3. Divergent differentiation in malignant soft tissue neoplasms: the paradigm of liposarcoma and malignant peripheral nerve sheath tumor.

    PubMed

    Pytel, Peter; Taxy, Jerome B; Krausz, Thomas

    2005-01-01

    In tumors clonality does not always translate into morphologic uniformity. While most sarcomas exhibit only one line of histologic differentiation, a minority may display a strikingly diverse phenotype in addition to the main lineage. This phenomenon not only presents a diagnostic problem but also raises questions about the commitment of tumor cells toward a specific phenotype. Among sarcomas, malignant peripheral nerve sheath tumor (MPNST) and dedifferentiated liposarcoma are two entities in which divergent differentiation is a relatively frequent event. Diagnostically it is crucial to recognize the "primary" sarcoma in such tumors correctly and distinguish it from the "secondary" divergent elements. The presence of the latter could be the first morphologic clue to a specific sarcoma type. Even though it may be difficult to explain the pathogenesis of divergent differentiation, divergence still illustrates that the phenotype of a tumor cell is not set in stone but can be modulated or switched by a number of factors.

  4. 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

  5. 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

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

    PubMed

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

    2013-11-01

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

  7. The Utility of a Tissue Slice Model System to Determine Breast Cancer Infectivity by Oncolytic Adenoviruses

    PubMed Central

    Pennington, Krista; Chu, Quyen D.; Curiel, David T.; Li, Benjamin D.L.; Mathis, J. Michael

    2010-01-01

    Background Due to advances in viral design, oncolytic adenoviruses have emerged as a promising approach for treatment of breast cancer. Tumor tissue slices offer a stringent model system for preclinical evaluation of adenovirus therapies, since the slices retain a morphology and phenotype that more closely resembles the in vivo setting than cell line cultures, and it has been shown to have utility in the evaluation of viral infectivity and replication. In this study, we evaluated the efficacy of viral infection and replication using a tropism-modified oncolytic adenovirus. Methods Breast tumor tissue slices were infected with a tropism-modified oncolytic adenovirus, and a wild-type adenovirus for comparison. Efficiency of infection was evaluated using fluorescent microscopy, as the viruses used have been modified to express red fluorescent protein. Replication of the viruses was evaluated with quantitative real-time PCR to assay viral E4 genome copy number, a surrogate indicator for the number of virions. The breast tumor tissue slices were evaluated for the expression of CD46 expression by immunohistochemistry. Results Infection and replication of our tropism modified oncolytic virus has been observed in breast cancer tissue slice model system and is comparative to wild-type virus. A qualitative increase in the number of cells showing RFP expression was observed correlating with increasing multiplicity of infection. Higher relative infectivity of the virus was observed in tumor tissue compared with normal breast tissue. Replication of the virus was demonstrated through increases in E4 copy number at 48 and 72 hours after infection in human breast tumor slices. Conclusions We have shown that a tropism modified oncolytic oncolytic adenovirus can infect and replicate in breast cancer tissue slices, which may be an important preclinical indicator for its therapeutic utility. PMID:20691986

  8. Thermal detection of a prevascular tumor embedded in breast tissue.

    PubMed

    Agyingi, Ephraim; Wiandt, Tamas; Maggelakis, Sophia A

    2015-10-01

    This paper presents a mathematical model of heat transfer in a prevascular breast tumor. The model uses the steady state temperature of the breast at the skin surface to determine whether there is an underlying tumor and if so, verifies whether the tumor is growing or dormant. The model is governed by the Pennes equations and we present numerical simulations for versions of the model in two and three dimensions.

  9. 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

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

    PubMed

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

    2011-10-01

    Promoter hypermethylation has been shown to be a common mechanism for inactivation of tumor suppressor genes in breast cancer. The aim of this study was to investigate the prevalence of Slit2 promoter hypermethylation in both the tumor and serum samples of breast cancer patients with ductal carcinoma in situ (DCIS) or invasive breast carcinoma (IBC). The methylation status of Slit2 was investigated in 210 tissue samples (15 breast with no pathological findings, 26 DCIS, and 169 IBC samples) and 123 corresponding serum samples (15 breast with no pathological findings, 26 DCIS, and 82 IBC samples) using methylation-specific polymerase chain reaction. Immunohistochemical staining for Slit2 was also performed using tissue microarray blocks to determine whether Slit2 promoter hypermethylation correlated with loss of Slit2 expression. Slit2 promoter hypermethylation was not detected in breast tissue and serum samples from patients with no pathological findings. DCIS or IBC showed a statistically higher frequency of Slit2 promoter hypermethylation compared to breast with no pathological findings in both the tissue and serum samples; however, there were no statistically significant differences between DCIS and IBC samples. Similar Slit2 promoter hypermethylation patterns were seen in the tissue samples and corresponding serum specimens (p < 0.001). Slit2 promoter hypermethylation was associated with loss of Slit2 expression. These results suggest that Slit2 promoter hypermethylation appears to be responsible for functionally silencing Slit2 expression. Slit2 promoter hypermethylation may be considered as a possible serum marker for early detection of breast cancer.

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

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

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

  12. Human decellularized adipose tissue scaffold as a model for breast cancer cell growth and drug treatments.

    PubMed

    Dunne, Lina W; Huang, Zhao; Meng, Weixu; Fan, Xuejun; Zhang, Ningyan; Zhang, Qixu; An, Zhiqiang

    2014-06-01

    Human adipose tissue extracellular matrix, derived through decellularization processing, has been shown to provide a biomimetic microenvironment for adipose tissue regeneration. This study reports the use of human adipose tissue-derived extracellular matrix (hDAM) scaffolds as a three-dimensional cell culturing system for the investigation of breast cancer growth and drug treatments. The hDAM scaffolds have similar extracellular matrix composition to the microenvironment of breast tissues. Breast cancer cells were cultured in hDAM scaffolds, and cell proliferation, migration, morphology, and drug responses were investigated. The growth profiles of multiple breast cancer cell lines cultured in hDAM scaffolds differed from the growth of those cultured on two-dimensional surfaces and more closely resembled the growth of xenografts. hDAM-cultured breast cancer cells also differed from those cultured on two-dimensional surfaces in terms of cell morphology, migration, expression of adhesion molecules, and sensitivity to drug treatment. Our results demonstrated that the hDAM system provides breast cancer cells with a biomimetic microenvironment in vitro that more closely mimics the in vivo microenvironment than existing two-dimensional and Matrigel three-dimensional cultures do, and thus can provide vital information for the characterization of cancer cells and screening of cancer therapeutics.

  13. A review of parameters for the bioelectrical characterization of breast tissue.

    PubMed

    Jossinet, J; Schmitt, M

    1999-04-20

    In the data set collected by the authors in freshly excised breast tissue, the admittance loci generally differed from circular arcs, rendering the calculation of the usual set of parameters impossible. Alternative parameters were used for the analysis of these data. The present study consists of the definition and evaluation of a set of such parameters aimed at the characterization and differentiation of breast tissues. These parameters were defined so that their calculation does not require the fit of circular arcs to the experimental points and is independent of any equivalent circuit model. The results of the statistical analysis showed significant differences between most of the tissue groups, especially between cancerous tissue and all the other groups, which confirmed that impedance spectroscopy can be considered as potentially suitable for breast cancer detection. PMID:10372147

  14. 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

  15. 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.

  16. Breast MRI scan

    MedlinePlus

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

  17. Comparison of the expression of 5 heat shock proteins in benign and malignant salivary gland tumor tissues.

    PubMed

    Wang, Guilan; Gu, Xiaolin; Chen, Li; Wang, Yinmei; Cao, Bin; E, Qun

    2013-04-01

    The objective of this study was to analyze the significance and potential value of heat shock proteins (HSPs) in salivary gland tumors. We found that expression of HSP60, HSP70, HSP86 and HSP84 were all upregulated in both salivary gland benign tumors and malignant tumors, and that the expression of HSP70, HSP86 and HSP84 was more greatly overexpressed in the malignant tumors (each P<0.01). For HSP27, expression was upregulated both in malignant and benign tumors, with less expression observed in malignant tumors (P<0.01). In malignant tumors, expression of HSP27 was negatively correlated with the age of the patients, size of the tumor tissue, occurrence of neural invasion and metastasis (each P<0.05). Additionally, in malignant tumors, HSP70 and HSP86 were both positively correlated with occurrence site, neural invasion and metastasis (each P<0.05), while HSP60 was only negatively correlated with the age of the patients (P<0.05). HSP86 was also positively correlated with malignant degree (P<0.01). In malignant tumors, the proliferation index (PI), which was marked by proliferating cell nuclear antigen (PCNA; PCNA-PI) was 49.95±14.569, which was significantly higher compared with that in benign tumors (P<0.001), which was in accordance with the upregulation of HSP70, HSP86 or HSP84; however, an adverse correlation was found between HSP27 expression and PCNA (each P<0.05). In conclusion, these results suggest that HSPs are involved in the occurrence and development of salivary gland tumors. HSP70, HSP86 and HSP84 retained the higher multiplication capability of the malignant tumor cells, however, HSP27 did not. Thus, the upregulation of HSP70, HSP86 and HSP84 and the downregulation of HSP27 may all be used as biomarkers of the occurrence and development of malignant salivary gland tumors. Moreover, the extremely high expression of HSP86 and HSP84 in benign tumors indicates the malignant transformation potential.

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

    PubMed Central

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

    1994-01-01

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

  19. Specific and non-specific folate binding protein in normal and malignant human tissues

    PubMed Central

    Corrocher, R.; De Sandre, G.; Ambrosetti, A.; Pachor, M. L.; Bambara, L. M.; Hoffbrand, A. V.

    1978-01-01

    Binding of tritiated folic acid by supernatants prepared from extracts of normal and leukaemic leucocytes, normal mucosa, and malignant tumours from different parts of the gastrointestinal tract has been measured using Sephadex-gel filtration and albumin-coated charcoal techniques. Non-specific binding (measured by Sephadex G-75 gel filtration) was almost invariably greater than specific binding measured by albumin-coated charcoal separation of bound and unbound folate. In nine normal leucocyte extracts, binding measured by Sephadex G-75 filtration ranged from 1·3 to 18·2 (mean 8·2) pg/mg protein and by albumin-coated charcoal from 1·0 to 14·8 (mean 6·7) pg/mg protein. Raised specific binding was found in the extracts from leucocytes of eight of 14 patients with chronic granulocytic leukaemia, in four substantially so (389, 121, 108, 59·7 pg/mg protein), but was only marginally increased in one of eight cases of acute myeloid leukaemia and in two of five cases of chronic lymphocytic leukaemia. Binding was normal in the extracts of all three cases of acute lymphoblastic leukaemia tested. Among the tissues of the gastrointestinal tract binding was greatest by the duodenal mucosa and liver. Extracts of carcinoma of the stomach and colon bound greater amounts of 3H-folic acid than the corresponding normal mucosal extracts but the differences were not large. Sephadex G-200 gel chromatography showed more than one binding peak in the extracts of liver and duodenum but only one peak in the other tissues of the gastrointestinal tract, and only one peak, of molecular weight either about 50 000 or over 200 000, in the leucocyte extracts. PMID:670421

  20. Malignant mesothelioma and duration of asbestos exposure: correlation with tissue mineral fibre content.

    PubMed

    Roggli, V L

    1995-06-01

    Among 441 cases of malignant mesothelioma in the author's files, there were 324 for whom reliable information was available regarding the duration of exposure to asbestos. Included were 298 pleural and 26 peritoneal mesotheliomas. The mean duration of exposure to asbestos was 23 +/- 14 years for all cases, and was not different for the pleural and peritoneal groups. Lung tissue was available for analysis of mineral fibre content in 94 cases. Linear regression analysis showed a significant correlation between duration of exposure and asbestos bodies per gramme of wet lung as determined by light microscopy, and between duration of exposure and total uncoated fibres (5 microns or greater in length) as well as commercial amphibole fibres per gramme as determined by scanning electron microscopy (P < 0.05). Individuals with direct exposures had on average higher asbestos contents than patients with indirect exposures. Furthermore, for each duration of exposure, shipyard workers had on average higher asbestos contents than non-shipyard workers (P < 0.05). Mesotheliomas are associated with a wide range of durations of exposure to asbestos and pulmonary asbestos burdens, and there is a rough correlation between duration of exposure and pulmonary commercial amphibole content.

  1. 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

  2. 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.

  3. Effects of simultaneous knockdown of HER2 and PTK6 on malignancy and tumor progression in human breast cancer cells.

    PubMed

    Ludyga, Natalie; Anastasov, Natasa; Rosemann, Michael; Seiler, Jana; Lohmann, Nadine; Braselmann, Herbert; Mengele, Karin; Schmitt, Manfred; Höfler, Heinz; Aubele, Michaela

    2013-04-01

    Breast cancer is the most common malignancy in women of the Western world. One prominent feature of breast cancer is the co- and overexpression of HER2 and protein tyrosine kinase 6 (PTK6). According to the current clinical cancer therapy guidelines, HER2-overexpressing tumors are routinely treated with trastuzumab, a humanized monoclonal antibody targeting HER2. Approximately, 30% of HER2-overexpressing breast tumors at least initially respond to the anti-HER2 therapy, but a subgroup of these tumors develops resistance shortly after the administration of trastuzumab. A PTK6-targeted therapy does not yet exist. Here, we show for the first time that the simultaneous knockdown in vitro, compared with the single knockdown of HER2 and PTK6, in particular in the trastuzumab-resistant JIMT-1 cells, leads to a significantly decreased phosphorylation of crucial signaling proteins: mitogen-activated protein kinase 1/3 (MAPK 1/3, ERK 1/2) and p38 MAPK, and (phosphatase and tensin homologue deleted on chromosome ten) PTEN that are involved in tumorigenesis. In addition, dual knockdown strongly reduced the migration and invasion of the JIMT-1 cells. Moreover, the downregulation of HER2 and PTK6 led to an induction of p27, and the dual knockdown significantly diminished cell proliferation in JIMT-1 and T47D cells. In vivo experiments showed significantly reduced levels of tumor growth following HER2 or PTK6 knockdown. Our results indicate a novel strategy also for the treatment of trastuzumab resistance in tumors. Thus, the inhibition of these two signaling proteins may lead to a more effective control of breast cancer.

  4. β-alanine suppresses malignant breast epithelial cell aggressiveness through alterations in metabolism and cellular acidity in vitro

    PubMed Central

    2014-01-01

    Background Deregulated energetics is a property of most cancer cells. This phenomenon, known as the Warburg Effect or aerobic glycolysis, is characterized by increased glucose uptake, lactate export and extracellular acidification, even in the presence of oxygen. β-alanine is a non-essential amino acid that has previously been shown to be metabolized into carnosine, which functions as an intracellular buffer. Because of this buffering capacity, we investigated the effects of β-alanine on the metabolic cancerous phenotype. Methods Non-malignant MCF-10a and malignant MCF-7 breast epithelial cells were treated with β-alanine at 100 mM for 24 hours. Aerobic glycolysis was quantified by measuring extracellular acidification rate (ECAR) and oxidative metabolism was quantified by measuring oxygen consumption rate (OCR). mRNA of metabolism-related genes was quantified by qRT-PCR with corresponding protein expression quantified by immunoblotting, or by flow cytometry which was verified by confocal microscopy. Mitochondrial content was quantified using a mitochondria-specific dye and measured by flow cytometry. Results Cells treated with β-alanine displayed significantly suppressed basal and peak ECAR (aerobic glycolysis), with simultaneous increase in glucose transporter 1 (GLUT1). Additionally, cells treated with β-alanine exhibited significantly reduced basal and peak OCR (oxidative metabolism), which was accompanied by reduction in mitochondrial content with subsequent suppression of genes which promote mitochondrial biosynthesis. Suppression of glycolytic and oxidative metabolism by β-alanine resulted in the reduction of total metabolic rate, although cell viability was not affected. Because β-alanine treatment reduces extracellular acidity, a constituent of the invasive microenvironment that promotes progression, we investigated the effect of β-alanine on breast cell viability and migration. β-alanine was shown to reduce both cell migration and proliferation

  5. 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.

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

    PubMed

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

    2013-03-01

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

  7. 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.

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

    PubMed

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

    2015-07-01

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

  9. Clinical Data as an Adjunct to Ultrasound Reduces the False-Negative Malignancy Rate in BI-RADS 3 Breast Lesions

    PubMed Central

    Ackermann, S.; Schoenenberger, C.-A.; Zanetti-Dällenbach, R.

    2016-01-01

    Purpose: Ultrasound (US) is a well-established diagnostic procedure for breast examination. We investigated the malignancy rate in solid breast lesions according to their BI-RADS classification with a particular focus on false-negative BI-RADS 3 lesions. We examined whether patient history and clinical findings could provide additional information that would help determine further diagnostic steps in breast lesions. Materials and Methods: We conducted a retrospective study by exploring US BI-RADS in 1469 breast lesions of 1201 patients who underwent minimally invasive breast biopsy (MIBB) from January 2002 to December 2011. Results: The overall sensitivity and specificity of BI-RADS classification was 97.4% and 66.4%, respectively, with a positive (PPV) and negative predictive value (NPV) of 65% and 98%, respectively. In 506 BI-RADS 3 lesions, histology revealed 15 malignancies (2.4% malignancy rate), which corresponds to a false-negative rate (FNR) of 2.6%. Clinical evaluation and patient requests critically influenced the further diagnostic procedure, thereby prevailing over the recommendation given by the BI-RADS 3 classification. Conclusion: Clinical criteria including age, family and personal history, clinical examination, mammography and patient choice ensure adequate diagnostic procedures such as short-term follow-up or MIBB in patients with lesions classified as US-BI-RADS 3. PMID:27689181

  10. Clinical Data as an Adjunct to Ultrasound Reduces the False-Negative Malignancy Rate in BI-RADS 3 Breast Lesions

    PubMed Central

    Ackermann, S.; Schoenenberger, C.-A.; Zanetti-Dällenbach, R.

    2016-01-01

    Purpose: Ultrasound (US) is a well-established diagnostic procedure for breast examination. We investigated the malignancy rate in solid breast lesions according to their BI-RADS classification with a particular focus on false-negative BI-RADS 3 lesions. We examined whether patient history and clinical findings could provide additional information that would help determine further diagnostic steps in breast lesions. Materials and Methods: We conducted a retrospective study by exploring US BI-RADS in 1469 breast lesions of 1201 patients who underwent minimally invasive breast biopsy (MIBB) from January 2002 to December 2011. Results: The overall sensitivity and specificity of BI-RADS classification was 97.4% and 66.4%, respectively, with a positive (PPV) and negative predictive value (NPV) of 65% and 98%, respectively. In 506 BI-RADS 3 lesions, histology revealed 15 malignancies (2.4% malignancy rate), which corresponds to a false-negative rate (FNR) of 2.6%. Clinical evaluation and patient requests critically influenced the further diagnostic procedure, thereby prevailing over the recommendation given by the BI-RADS 3 classification. Conclusion: Clinical criteria including age, family and personal history, clinical examination, mammography and patient choice ensure adequate diagnostic procedures such as short-term follow-up or MIBB in patients with lesions classified as US-BI-RADS 3.

  11. 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

  12. Demographic and practice characteristics of pathologists who enjoy breast tissue interpretation.

    PubMed

    Oster, Natalia V; Geller, Berta M; Carney, Patricia A; Reisch, Lisa M; Onega, Tracy; Weaver, Donald L; Frederick, Paul; Elmore, Joann G

    2015-04-01

    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 comparing pathologist assessments of a set of 60 cases with consensus assessments of the same cases made 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 have 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy

    PubMed Central

    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.

    2015-01-01

    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

  18. Non-enzymatic, serum-free tissue culture of pre-invasive breast lesions for spontaneous generation of mammospheres.

    PubMed

    Espina, Virginia; Edmiston, Kirsten H; Liotta, Lance A

    2014-11-08

    Breast ductal carcinoma in situ (DCIS), by definition, is proliferation of neoplastic epithelial cells within the confines of the breast duct, without breaching the collagenous basement membrane. While DCIS is a non-obligate precursor to invasive breast cancers, the molecular mechanisms and cell populations that permit progression to invasive cancer are not fully known. To determine if progenitor cells capable of invasion existed within the DCIS cell population, we developed a methodology for collecting and culturing sterile human breast tissue at the time of surgery, without enzymatic disruption of tissue. Sterile breast tissue containing ductal segments is harvested from surgically excised breast tissue following routine pathological examination. Tissue containing DCIS is placed in nutrient rich, antibiotic-containing, serum free medium, and transported to the tissue culture laboratory. The breast tissue is further dissected to isolate the calcified areas. Multiple breast tissue pieces (organoids) are placed in a minimal volume of serum free medium in a flask with a removable lid and cultured in a humidified CO₂ incubator. Epithelial and fibroblast cell populations emerge from the organoid after 10 - 14 days. Mammospheres spontaneously form on and around the epithelial cell monolayer. Specific cell populations can be harvested directly from the flask without disrupting neighboring cells. Our non-enzymatic tissue culture system reliably reveals cytogenetically abnormal, invasive progenitor cells from fresh human DCIS lesions.

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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…

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. X-ray scattering for classifying tissue types associated with breast disease

    SciTech Connect

    Sidhu, Sabeena; Siu, Karen K. W.; Falzon, Gregory; Nazaretian, Simon; Hart, Stewart A.; Fox, Jane G.; Susil, Beatrice J.; Lewis, Robert A.

    2008-10-15

    Collagen types I and III can be characterized at the molecular level (at the tens to hundreds of nanometers scale) using small angle x-ray scattering (SAXS). Although collagen fibril structural parameters at this length scale have shown differences between diseased and nondiseased breast tissues, a comprehensive analysis involving a multitude of features with a large (>50) patient cohort has not previously been investigated. Breast tissue samples were excised from 80 patients presenting with either a breast lump or reduction mammoplasty. From these, invasive carcinoma, benign tissue, and normal parenchyma were analyzed. Parameters related to collagen structure, including longitudinal (axial) and lateral (equatorial) features, polar angle features, total scattering intensity, and tissue heterogeneity effects, were extracted from the SAXS patterns and examined. The amplitude of the third-order axial peak and the total scattering intensity (amorphous scatter) showed the most separation between tissue groups and a classification model using these two parameters demonstrated an accuracy of over 95% between invasive carcinoma and mammoplasty patients. Normal tissue taken from disease-free patients (mammoplasty) and normal tissue taken from patients with presence of disease showed significant differences, suggesting that SAXS may provide different diagnostic information from that of conventional histopathology.

  10. Dissecting the Origin of Breast Cancer Subtype Stem Cell and the Potential Mechanism of Malignant Transformation

    PubMed Central

    Liu, Dianming; Wang, Shuyuan; Yu, Xuexin; Dai, Enyu; Wang, Jing; Wang, Lihong; Jiang, Wei

    2016-01-01

    Background Breast cancer is the most common incident form of cancer in women including different subtypes. Cancer stem cells (CSCs) have been confirmed to exist in breast cancer. But the research on the origin of breast cancer subtype stem cells (BCSSCs) is still inadequate. Methods We identified the putative origin cells of BCSSCs through comparing gene signatures between BCSSCs and normal mammary cells from multiple perspectives: common signature, expression consistency, functional similarity and shortest path length. First, the potential origin cells were ranked according to these measures separately. Then Q statistic was employed to combine all rank lists into a unique list for each subtype, to prioritize the origin cells for each BCSSC. Next, we identified origin-related gene modules through integrating functional interaction network with differentially expressed genes. Finally, transcription factors of significant gene modules were predicted by MatchTM. Results The results showed that Luminal A CSC was most relevant to luminal progenitor cell or mature luminal cell; luminal B and HER2 CSC were most relevant to bipotent-enriched progenitor cell; basal-like CSC was most relevant to bipotent-enriched progenitor cell or mature luminal cell. Network modules analysis revealed genes related to mitochondrial respiratory chain (MRC) were significantly dysregulated during the origin of luminal B CSC. In addition, SOX10 emerged as a key regulator of MRC. Conclusions Our study supports substantive evidence for the possible origin of four kinds of BCSSCs. Dysfunction of MRC may contribute to the origin of luminal B CSC. These findings may have important implications to treat and prevent breast cancer. PMID:27768723

  11. 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.

  12. Detection of alterations in chromosomes 16 and 1 by fluorescence in situ hybridization in breast tumors cytologically or histologically equivocal for malignancy.

    PubMed

    Tsuda, H; Takarabe, T; Shimamura, K; Hirohashi, S

    1998-01-01

    Structural and numerical alterations, and fusion of chromosomes 16 and 1 have been shown to occur frequently in low-grade breast carcinoma, but not in benign papilloma by fluorescence in situ hybridization (FISH). We carried out FISH analysis of 11 benign tumors and 3 breast tumors for which the preoperative diagnosis was equivocal for cancer. In 11 benign lesions and 1 benign phyllode tumor which was cytologically equivocal for malignancy, alteration of the chromosome 16 or 1 signal was not detected as a predominant cell clone. On the other hand, in 1 grade 1 invasive ductal carcinoma which was judged as equivocal for malignancy and 1 marked adenosis with atypia which was judged as malignant by fine-needle aspiration cytology, the majority of constituent tumor cells showed fusion of chromosomes 16 and 1. Detection of alterations in chromosomes 16 and 1 as a predominant clone was suggested to be an indicator of lesion malignancy even though the grade of malignancy may not be high. As a supportive diagnostic procedure, FISH analysis may give information about the nature of lesions, when the lesions are clinically or pathologically equivocal for cancer. PMID:9769473

  13. 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.

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

    PubMed

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

    2015-11-10

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

  15. Immunohistochemistry Study of P53 and C-erbB-2 Expression in Trophoblastic Tissue and Their Predictive Values in Diagnosing Malignant Progression of Simple Molar Pregnancy

    PubMed Central

    Hasanzadeh, Malihe; Sharifi, Norrie; Farazestanian, Marjaneh; Nazemian, Seyed Saman; Madani Sani, Faezeh

    2016-01-01

    Background Finding a tumor marker to predict the aggressive behavior of molar pregnancy in early stages has yet been a topic for studies. Objectives In this survey we planned to study patients with molar pregnancy to 1) assess the p53 and c-erbB-2 expression in trophoblastic tissue, 2) to study the relationship between their expression intensity and progression of a molar pregnancy to gestational trophoblastic neoplasia, and 3) to determine a cut off value for the amount of p53 and c-erbB-2 expression which might correlate with aggressive behavior of molar pregnancy. Patients and Methods In a prospective cross sectional study by using a high accuracy technique EnVision Tm system for immunohistochemistry staining of molar pregnancy samples, we evaluated p53 and c-erbB-2 expression in cytotrophoblast and syncytiotrophoblast and the correlation of their expression with progression of molar pregnancy to gestational trophoblastic neoplasia (GTN). Normal prostatic tissue and Breast cancer tissue were used as positive controls. Results We studied 28 patients with simple molar pregnancy (SMP) and 30 with GTN. Cytotrophobalst had significantly higher expression of p53 and c-erbB-2 and syncytiotrophoblast had greater expression of p53 in GTN group as compared to SMP group. The cut off values for percentage of p53 positive immunostained cytotrophoblast and syncytiotrophoblast were 5.5% and 2.5%. In c-erbB-2 positive membranous stained cytotrophoblast the cut off was 12.5%. Conclusions Our data suggests that over expression of p53 and c-erbB-2 is associated with malignant progression of molar pregnancy. We encountered that high expression of p53 and c-erbB-2 in trophoblastic cells could predict gestational trophoblastic neoplasia during the early stages. PMID:27703642

  16. Diffuse optical spectroscopy measurements of healing in breast tissue after core biopsy: case study

    PubMed Central

    Tanamai, Wendy; Chen, Cynthia; Siavoshi, Sara; Cerussi, Albert; Hsiang, David; Butler, John; Tromberg, Bruce

    2010-01-01

    Diffuse optical spectroscopy (DOS) has been used to monitor and predict the effects of neoadjuvant (i.e., presurgical) chemotherapy in breast cancer patients in several pilot studies. Because patients with suspected breast cancers undergo biopsy prior to treatment, it is important to understand how biopsy trauma influences DOS measurements in the breast. The goal of this study was to measure the effects of a standard core breast biopsy on DOS measurements of tissue deoxyhemoglobin, hemoglobin, water, and bulk lipid concentrations. We serially monitored postbiopsy effects in the breast tissue in a single subject (31-year-old premenopausal female) with a 37×18×20 mm fibroadenoma. A baseline measurement and eight weekly postbiopsy measurements were taken with a handheld DOS imaging instrument. Our instrument used frequency domain photon migration combined with broadband steady-state spectroscopy to characterize tissues via quantitative measurements of tissue absorption and reduced scattering coefficients from 650 to 1000 nm. The concentrations of significant near-infrared (NIR) absorbers were mapped within a 50 cm2 area over the biopsied region. A 2-D image of a contrast function called the tissue optical index (TOI=deoxyhemoglobin×water/bulk lipid) was generated and revealed that a minimum of 14 days postbiopsy was required to return TOI levels in the biopsied area to their prebiopsy levels. Changes in the TOI images of the fibroadenoma also reflected the progression of the patient’s menstrual cycle. DOS could therefore be useful in evaluating both wound-healing response and the effects of hormone and hormonal therapies in vivo. PMID:19256712

  17. “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

  18. 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. PMID:27190645

  19. 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 ...

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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

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

    NASA Astrophysics Data System (ADS)

    Marks, Fay A.

    1996-04-01

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

  6. In vivo near-infrared spectral detection of pressure-induced changes in breast tissue

    NASA Astrophysics Data System (ADS)

    Jiang, Shudong; Pogue, Brian W.; Paulsen, Keith D.; Kogel, Christine; Poplack, Steven P.

    2003-07-01

    A diffuse near-infrared tomography system was used to measure dynamic changes in the absolute optical properties of the human breast that were induced through pressure applied to the tissue surface. Results from five subjects show that absorption and scattering coefficients changed measurably when pressure was increased and that these relative changes correlated with the subjects' body-mass index, indicating that the effect depends on tissue composition. Fitting the absolute absorption and scattering coefficients at six wavelengths to the molar absorption spectra of the three predominant chromophores revealed that both the average total hemoglobin and oxygen saturation increased by 10%, while water concentration decreased by more than 12%. These changes indicate that the pressure-induced variation is likely due to water displacement and vascular volume increase in the region being imaged, for mild application of pressure to the breast. These results suggest that the pressure applied during optical measurements of tissue may alter the tissue physiology, and care should be taken to factor this effect into the design of optical medical instrumentation. In addition, the technique provides a unique approach to measuring tissue elastic changes in vivo in the female breast and may offer a new method for dynamic contrast imaging based on elasto-optical measurements.

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

    PubMed

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

    2016-03-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

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

  9. 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

  10. 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

  11. 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.

  12. Trends in Breast Tissue Sampling and Pathology Diagnoses among Women Undergoing Mammography in the U.S.: A Report from the Breast Cancer Surveillance Consortium

    PubMed Central

    Allison, Kimberly H.; Abraham, Linn A.; Weaver, Donald L.; Tosteson, Anna NA; Nelson, Heidi D.; Onega, Tracy; Geller, Berta M; Kerlikowske, Karla; Carney, Patricia A.; Ichikawa, Laura E.; Buist, Diana S.M.; Elmore, Joann G.

    2015-01-01

    Background Current data on the pathologic diagnoses of breast biopsy after mammography can inform patients, clinicians, and researchers about important population trends. Methods Breast Cancer Surveillance Consortium data on 4,020,140 mammograms between 1996 and 2008 were linked to 76,567 pathology specimens. Trends in diagnoses in biopsies by time and risk factors (patient age, breast density, and family history of breast cancer) were examined for screening and diagnostic mammography (performed for a breast symptom or short interval follow-up). Results Of the total mammograms, 88.5% were screening and 11.5% diagnostic; 1.2% of screening and 6.8% of diagnostic mammograms were followed by biopsies. The frequency of biopsies over time was stable after screening mammograms, but increased after diagnostic mammograms. For biopsies obtained after screening, frequencies of invasive carcinoma increased over time for women aged 40–49 and 60–69, DCIS increased for 40–69, while benign diagnoses decreased for all ages. No trends in pathology diagnoses were found following diagnostic mammograms. Dense breast tissue was associated with high-risk lesions and DCIS relative to non-dense breast tissue. Family history of breast cancer was associated with DCIS and invasive cancer. Conclusions While the frequency of breast biopsy after screening mammography has not changed over time, the percentages of biopsies with DCIS and invasive cancer diagnoses have increased. Among biopsies following mammography, women with dense breasts or family history of breast cancer were more likely to have high-risk lesions or invasive cancer. These findings are relevant to breast cancer screening and diagnostic practices. PMID:25603785

  13. Extraction of RNA from archival tissues and measurement of thrombospondin-1 mRNA in normal, dysplastic, and malignant oral tissues.

    PubMed

    Macluskey, M; Baillie, R; Morrow, H; Schor, S L; Schor, A M

    2006-04-01

    Thrombospondin-1 (TSP-1) is an extracellular matrix glycoprotein implicated in the regulation of angiogenesis and tumour development. Our objectives were to ascertain the quantity and quality of RNA extracted from archival, formalin-fixed, paraffin embedded, oral tissues and their application in measuring the concentrations of TSP-1 mRNA in these tissues. We compared three techniques of isolation of RNA as well as related experimental variables. TSP-1 mRNA was measured in specimens of normal, dysplastic, and malignant oral tissues by real-time reverse transcriptase polymerase chain reaction (RT-PCR). RNA suitable for analysis by real-time RT-PCR was obtained by the three techniques tested, although the yield varied depending on the protocol used (range 0.2-3.6 microg/mm(3)). The mean (S.D.) concentrations of TSP-1 mRNA relative to 18S were 21.1 (7.2) in normal oral tissues (n=9), 11.0 (8.2) in dysplastic tissue (n=8) and 7.3 (5.3) in carcinomatous tissue (n=17). The difference between normal and carcinomatous specimens was significant (p=0.01). This reduction in expression of TSP-1 mRNA from normal to dysplasia to carcinoma may favour the angiogenic drive that accompanies the development of oral tumours.

  14. Comparison of 3 alpha-hydroxysteroid dehydrogenase activities in the microsomal fractions of hyperplastic, malignant and normal human prostatic tissues.

    PubMed

    Hudson, R W

    1984-04-01

    The conversion of dihydrotestosterone (DHT) to 3 alpha-androstanediol (3 alpha-adiol) was studied using the microsomal fractions of 15 hyperplastic, 5 malignant and 6 normal human prostatis tissues. Standard assay conditions were: 0.2 microM DHT, 1.0 mM NADPH, 1.0 mM NADH, 2.0 mM EDTA and the microsomal fractions equivalent to 200 mg of prostatic tissue, in 0.1 M MES buffer, pH 6.5. Under the conditions of this assay, the back-conversion of 3 alpha-adiol to DHT or the conversion of DHT to androstanediol were negligible. Optimum enzyme activity was achieved under standard assay conditions. In the absence of EDTA: enzyme activity was 65% of the standard assay; activity was diminished further by 2 mM Ca2+ and virtually eliminated by 2 mM Mg2+ or 2 microM Zn2+. Activity in the absence of either NADPH or NADH was only 50% of the activities seen in the presence of both cofactors. The pH optimum of the enzyme was between 6.0 and 6.5. The apparent Km values of the enzymes in hyperplastic, malignant and normal tissues were 0.03, 0.02 and 0.03 microM, respectively. The Vmax values for these tissues were 6.0 +/- 2.1, 1.6 +/- 0.5 and 14.0 +/- 3.0 pmol/mg protein/20 min incubation, respectively. The results of these experiments offer further explanation for the differences in DHT and 3 alpha-adiol levels seen in the 3 prostatic tissues.

  15. A methyl-deviator epigenotype of estrogen receptor-positive breast carcinoma is associated with malignant biology.

    PubMed

    Killian, J Keith; Bilke, Sven; Davis, Sean; Walker, Robert L; Jaeger, Erich; Killian, M Scott; Waterfall, Joshua J; Bibikova, Marina; Fan, Jian-Bing; Smith, William I; Meltzer, Paul S

    2011-07-01

    We broadly profiled DNA methylation in breast cancers (n = 351) and benign parenchyma (n = 47) for correspondence with disease phenotype, using FFPE diagnostic surgical pathology specimens. Exploratory analysis revealed a distinctive primary invasive carcinoma subclass featuring extreme global methylation deviation. Subsequently, we tested the correlation between methylation remodeling pervasiveness and malignant biological features. A methyl deviation index (MDI) was calculated for each lesion relative to terminal ductal-lobular unit baseline, and group comparisons revealed that high-grade and short-survival estrogen receptor-positive (ER(+)) cancers manifest a significantly higher MDI than low-grade and long-survival ER(+) cancers. In contrast, ER(-) cancers display a significantly lower MDI, revealing a striking epigenomic distinction between cancer hormone receptor subtypes. Kaplan-Meier survival curves of MDI-based risk classes showed significant divergence between low- and high-risk groups. MDI showed superior prognostic performance to crude methylation levels, and MDI retained prognostic significance (P < 0.01) in Cox multivariate analysis, including clinical stage and pathological grade. Most MDI targets individually are significant markers of ER(+) cancer survival. Lymphoid and mesenchymal indexes were not substantially different between ER(+) and ER(-) groups and do not explain MDI dichotomy. However, the mesenchymal index was associated with ER(+) cancer survival, and a high lymphoid index was associated with medullary carcinoma. Finally, a comparison between metastases and primary tumors suggests methylation patterns are established early and maintained through disease progression for both ER(+) and ER(-) tumors.

  16. 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.

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

    PubMed

    Alani, Harith A; Balalaa, Nahed

    2013-10-01

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

  18. 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.

  19. 2-Methoxyestradiol inhibits progesterone-dependent tissue factor expression and activity in breast cancer cells.

    PubMed

    Quezada, Marisol; Diaz, Jorge; Henriquez, Soledad; Bravo, Maria Loreto; Aranda, Evelyn; Oliva, Barbara; Villalon, Manuel; Kato, Sumie; Cuello, Mauricio A; Brosens, Jan J; Lange, Carol A; Owen, Gareth I

    2010-06-01

    2-Methoxyestradiol (2ME) is an endogenous metabolite of 17β-estradiol with antiangiogenic and antitumor properties, although its mechanisms of action remain unclear. Progestins in hormone replacement therapy increase the risk of breast cancer. Progesterone also enhances the procoagulant activity and invasive potential of progesterone receptor (PR)-positive breast cancer cell lines, an effect largely mediated by induction of tissue factor (TF), the cellular activator of the coagulation cascade. Here we show that 2ME abrogates the induction TF expression in progesterone-treated breast cancer cells via a mechanism that does not involve the estrogen receptor. Instead, we demonstrate that by selectively antagonizing ERK1/2 signaling in breast cancer cells, 2ME limits the transactivation potential of ligand-bound PR and inhibits the expression of endogenous progesterone targets, such as TF and signal transducer and activator of transcription 5. We further demonstrate that 2ME can alter the phosphorylation status of PR. Thus, 2ME prevents progesterone-dependent increase in breast cancer cell invasiveness and procoagulant activity by uncoupling PR from the ERK1/2 signal transduction pathway.

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

    PubMed Central

    Mohammadi, Mehrnoosh; Riyahi Bakhtiari, Alireza; Khodabandeh, Saber

    2014-01-01

    Breast cancer is the major cause of cancer morbidity and mortality between women in the world. Metals involved in environmental toxicology are closely related to tumor growth and cancer. On the other hand, some metals such as selenium have anticarcinogenic properties. The aim of this study is to determine the concentration of cadmium, lead, mercury, and selenium in separated parts of tegmen, tumor, tumor adiposity, and tegmen adiposity of 14 breast cancer tissues which have been analyzed by graphite furnace atomic absorption (AA-670) and ICP-OES (ULTIMA 2CE). Our results show that Se and Hg have maximum and minimum concentration, respectively. Statistical analysis reveals no significant differences between metal accumulations in different parts of cancer tissues (P > 0.05) and this observation might be due to the close relation of separated parts of fatty breast organ. Thus, we could conclude that a high level of these heavy metals is accumulated in Iranian cancerous breasts and their presence can be one of the reasons of cancer appearance. PMID:24659998

  1. 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