Molecular Modification of Metadherin/MTDH Impacts the Sensitivity of Breast Cancer to Doxorubicin.

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Zhenchuan Song

Full Text Available Breast cancer is a leading cause of death in women and with an increasing worldwide incidence. Doxorubicin, as a first-line anthracycline-based drug is conventional used on breast cancer clinical chemotherapy. However, the drug resistances limited the curative effect of the doxorubicin therapy in breast cancer patients, but the molecular mechanism determinants of breast cancer resistance to doxorubicin chemotherapy are not fully understood. In order to explore the association between metadherin (MTDH and doxorubicin sensitivity, the differential expressions of MTDH in breast cancer cell lines and the sensitivity to doxorubicin of breast cancer cell lines were investigated.The mRNA and protein expression of MTDH were determined by real-time PCR and Western blot in breast cancer cells such as MDA-MB-231, MCF-7, MDA-MB-435S, MCF-7/ADR cells. Once MTDH gene was knocked down by siRNA in MCF-7/ADR cells and overexpressed by MTDH plasmid transfection in MDA-MB-231 cells, the cell growth and therapeutic sensitivity of doxorubicin were evaluated using MTT and the Cell cycle assay and apoptosis rate was determined by flow cytometry.MCF-7/ADR cells revealed highly expressed MTDH and MDA-MB-231 cells had the lowest expression of MTDH. After MTDH gene was knocked down, the cell proliferation was inhibited, and the inhibitory rate of cell growth and apoptosis rate were enhanced, and the cell cycle arrest during the G0/G1 phase in the presence of doxorubicin treatment. On the other hand, the opposite results were observed in MDA-MB-231 cells with overexpressed MTDH gene.MTDH gene plays a promoting role in the proliferation of breast cancer cells and its high expression may be associated with doxorubicin sensitivity of breast cancer.

Method of microbially producing metal gallate spinel nano-objects, and compositions produced thereby

Science.gov (United States)

Duty, Chad E.; Jellison, Jr., Gerald E.; Love, Lonnie J.; Moon, Ji Won; Phelps, Tommy J.; Ivanov, Ilia N.; Kim, Jongsu; Park, Jehong; Lauf, Robert

2018-01-16

A method of forming a metal gallate spinel structure that includes mixing a divalent metal-containing salt and a gallium-containing salt in solution with fermentative or thermophilic bacteria. In the process, the bacteria nucleate metal gallate spinel nano-objects from the divalent metal-containing salt and the gallium-containing salt without requiring reduction of a metal in the solution. The metal gallate spinel structures, as well as light-emitting structures in which they are incorporated, are also described.

Fuel cells with doped lanthanum gallate electrolyte

Energy Technology Data Exchange (ETDEWEB)

Feng Man [Texas Univ., Austin, TX (United States). Center for Materials Science and Engineering; Goodenough, J.B. [Texas Univ., Austin, TX (United States). Center for Materials Science and Engineering; Huang Keqin [Texas Univ., Austin, TX (United States). Center for Materials Science and Engineering; Milliken, C. [Cerematec, Inc., Salt Lake City, UT (United States)

1996-11-01

Single cells with doped lanthanum gallate electrolyte material were constructed and tested from 600 to 800 C. Both ceria and the electrolyte material were mixed with NiO powder respectively to form composite anodes. Doped lanthanum cobaltite was used exclusively as the cathode material. While high power density from the solid oxide fuel cells at 800 C was achieved, our results clearly indicate that anode overpotential is the dominant factor in the power loss of the cells. Better anode materials and anode processing methods need to be found to fully utilize the high ionic conductivity of the doped lanthanum gallate and achieve higher power density at 800 C from solid oxide fuel cells. (orig.)

The Immunomodulatory Potential of Selected Bioactive Plant-Based Compounds in Breast Cancer: A Review.

Science.gov (United States)

Baraya, Yushau Shuaibu; Wong, Kah Keng; Yaacob, Nik Soriani

2017-01-01

Breast cancer has continued to cause high cancer death rates among women worldwide. The use of plants' natural products in breast cancer treatment has received more attention in recent years due to their potentially wider safety margin and the potential to complement conventional chemotherapeutic drugs. Plantbased products have demonstrated anticancer potential through different biological pathways including modulation of the immune system. Immunomodulatory properties of medicinal plants have been shown to mitigate breast cancer cell growth. Different immune cell types participate in this process especially cytotoxic T cells and natural killer cells, and cytokines including chemokines and tumor necrosis factor-α. Medicinal plants such as Glycyrrhiza glabra, Uncaria tomentosa, Camellia sinensis, Panax ginseng, Prunus armenaica (apricot), Allium sativum, Arctium lappa and Curcuma longa were reported to hold strong potential in breast cancer treatment in various parts of the world. Interestingly, research findings have shown that these plants possess bioactive immunomodulators as their main constituents producing the anticancer effects. These immunomodulatory compounds include ajoene, arctigenin, β-carotene, curcumin, epigallocatechin-3-gallate, ginsan, glabridin and quinic acid. In this review, we discussed the ability of these eight immunomodulators in regulating the immune system potentially applicable in breast cancer treatment via anti-inflammatory (curcumin, arctigenin, glabridin and ajoene) and lymphocytes activation (β-carotene, epigallocatechin-3-gallate, quinic acid and ginsan) properties, as well as future research direction in their use for breast cancer treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Uncovering the Lactobacillus plantarum WCFS1 Gallate Decarboxylase Involved in Tannin Degradation

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Jiménez, Natalia; Curiel, José Antonio; Reverón, Inés; de las Rivas, Blanca

2013-01-01

Lactobacillus plantarum is a lactic acid bacterium able to degrade tannins by the subsequent action of tannase and gallate decarboxylase enzymes. The gene encoding tannase had previously been identified, whereas the gene encoding gallate decarboxylase is unknown. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of gallic-acid induced L. plantarum extracts showed a 54-kDa protein which was absent in the uninduced cells. This protein was identified as Lp_2945, putatively annotated UbiD. Homology searches identified ubiD-like genes located within three-gene operons which encoded the three subunits of nonoxidative aromatic acid decarboxylases. L. plantarum is the only bacterium in which the lpdC (lp_2945) gene and the lpdB and lpdD (lp_0271 and lp_0272) genes are separated in the chromosome. Combination of extracts from recombinant Escherichia coli cells expressing the lpdB, lpdC, and lpdC genes demonstrated that LpdC is the only protein required to yield gallate decarboxylase activity. However, the disruption of these genes in L. plantarum revealed that the lpdB and lpdC gene products are essential for gallate decarboxylase activity. Similar to L. plantarum tannase, which exhibited activity only in esters derived from gallic and protocatechuic acids, purified His6-LpdC protein from E. coli showed decarboxylase activity against gallic and protocatechuic acids. In contrast to the tannase activity, gallate decarboxylase activity is widely present among lactic acid bacteria. This study constitutes the first genetic characterization of a gallate decarboxylase enzyme and provides new insights into the role of the different subunits of bacterial nonoxidative aromatic acid decarboxylases. PMID:23645198

Unique proteomic signature for radiation sensitive patients; a comparative study between normo-sensitive and radiation sensitive breast cancer patients

Energy Technology Data Exchange (ETDEWEB)

Skiöld, Sara [Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm (Sweden); Azimzadeh, Omid [Institute of Radiation Biology, German Research Center for Environmental Health, Helmholtz Zentrum München (Germany); Merl-Pham, Juliane [Research Unit Protein Science, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg (Germany); Naslund, Ingemar; Wersall, Peter; Lidbrink, Elisabet [Division of Radiotherapy, Radiumhemmet, Karolinska University Hospital, Stockholm (Sweden); Tapio, Soile [Institute of Radiation Biology, German Research Center for Environmental Health, Helmholtz Zentrum München (Germany); Harms-Ringdahl, Mats [Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm (Sweden); Haghdoost, Siamak, E-mail: Siamak.Haghdoost@su.se [Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm (Sweden)

2015-06-15

Highlights: • The unique protein expression profiles were found that separate radiosensitive from normal sensitive breast cancer patients. • The oxidative stress response, coagulation properties and acute phase response suggested to be the hallmarks of radiation sensitivity. - Abstract: Radiation therapy is a cornerstone of modern cancer treatment. Understanding the mechanisms behind normal tissue sensitivity is essential in order to minimize adverse side effects and yet to prevent local cancer reoccurrence. The aim of this study was to identify biomarkers of radiation sensitivity to enable personalized cancer treatment. To investigate the mechanisms behind radiation sensitivity a pilot study was made where eight radiation-sensitive and nine normo-sensitive patients were selected from a cohort of 2914 breast cancer patients, based on acute tissue reactions after radiation therapy. Whole blood was sampled and irradiated in vitro with 0, 1, or 150 mGy followed by 3 h incubation at 37 °C. The leukocytes of the two groups were isolated, pooled and protein expression profiles were investigated using isotope-coded protein labeling method (ICPL). First, leukocytes from the in vitro irradiated whole blood from normo-sensitive and extremely sensitive patients were compared to the non-irradiated controls. To validate this first study a second ICPL analysis comparing only the non-irradiated samples was conducted. Both approaches showed unique proteomic signatures separating the two groups at the basal level and after doses of 1 and 150 mGy. Pathway analyses of both proteomic approaches suggest that oxidative stress response, coagulation properties and acute phase response are hallmarks of radiation sensitivity supporting our previous study on oxidative stress response. This investigation provides unique characteristics of radiation sensitivity essential for individualized radiation therapy.

Unique proteomic signature for radiation sensitive patients; a comparative study between normo-sensitive and radiation sensitive breast cancer patients

International Nuclear Information System (INIS)

Skiöld, Sara; Azimzadeh, Omid; Merl-Pham, Juliane; Naslund, Ingemar; Wersall, Peter; Lidbrink, Elisabet; Tapio, Soile; Harms-Ringdahl, Mats; Haghdoost, Siamak

2015-01-01

Highlights: • The unique protein expression profiles were found that separate radiosensitive from normal sensitive breast cancer patients. • The oxidative stress response, coagulation properties and acute phase response suggested to be the hallmarks of radiation sensitivity. - Abstract: Radiation therapy is a cornerstone of modern cancer treatment. Understanding the mechanisms behind normal tissue sensitivity is essential in order to minimize adverse side effects and yet to prevent local cancer reoccurrence. The aim of this study was to identify biomarkers of radiation sensitivity to enable personalized cancer treatment. To investigate the mechanisms behind radiation sensitivity a pilot study was made where eight radiation-sensitive and nine normo-sensitive patients were selected from a cohort of 2914 breast cancer patients, based on acute tissue reactions after radiation therapy. Whole blood was sampled and irradiated in vitro with 0, 1, or 150 mGy followed by 3 h incubation at 37 °C. The leukocytes of the two groups were isolated, pooled and protein expression profiles were investigated using isotope-coded protein labeling method (ICPL). First, leukocytes from the in vitro irradiated whole blood from normo-sensitive and extremely sensitive patients were compared to the non-irradiated controls. To validate this first study a second ICPL analysis comparing only the non-irradiated samples was conducted. Both approaches showed unique proteomic signatures separating the two groups at the basal level and after doses of 1 and 150 mGy. Pathway analyses of both proteomic approaches suggest that oxidative stress response, coagulation properties and acute phase response are hallmarks of radiation sensitivity supporting our previous study on oxidative stress response. This investigation provides unique characteristics of radiation sensitivity essential for individualized radiation therapy

Sensitivity of enhanced MRI for the detection of breast cancer: new, multicentric, residual, and recurrent

International Nuclear Information System (INIS)

Davis, P.L.; McCarty, K.S. Jr.

1997-01-01

Magnetic resonance imaging (MRI) of the breast brings the advantages of high resolution cross-sectional imaging to breast cancer diagnosis, treatment and research: improved cancer detection, staging, selection of therapy, evaluation of therapeutic response in vivo, detection of recurrence, and even the development of new therapies. Until now breast cancer treatment and research has been impeded by the limited means of evaluating the breast cancer in vivo: primarily clinical palpation and mammography of the breast tumor. A review of the initial studies shows that with the use of paramagnetic contrast agents, MRI has a sensitivity of 96 % for detecting breast cancers. MRI detects multicentric disease with a sensitivity of 98 %, superior to any other modality. The ability of MRI to detect recurrent local breast cancer in the conservatively treated breast is nearly 100 %. MRI is capable of monitoring tumor response to chemotherapy and actually guiding therapeutic interventions such as interstitial laser photocoagulation. (orig.)

Understanding drugs in breast cancer through drug sensitivity screening.

Science.gov (United States)

Uhr, Katharina; Prager-van der Smissen, Wendy J C; Heine, Anouk A J; Ozturk, Bahar; Smid, Marcel; Göhlmann, Hinrich W H; Jager, Agnes; Foekens, John A; Martens, John W M

2015-01-01

With substantial numbers of breast tumors showing or acquiring treatment resistance, it is of utmost importance to develop new agents for the treatment of the disease, to know their effectiveness against breast cancer and to understand their relationships with other drugs to best assign the right drug to the right patient. To achieve this goal drug screenings on breast cancer cell lines are a promising approach. In this study a large-scale drug screening of 37 compounds was performed on a panel of 42 breast cancer cell lines representing the main breast cancer subtypes. Clustering, correlation and pathway analyses were used for data analysis. We found that compounds with a related mechanism of action had correlated IC50 values and thus grouped together when the cell lines were hierarchically clustered based on IC50 values. In total we found six clusters of drugs of which five consisted of drugs with related mode of action and one cluster with two drugs not previously connected. In total, 25 correlated and four anti-correlated drug sensitivities were revealed of which only one drug, Sirolimus, showed significantly lower IC50 values in the luminal/ERBB2 breast cancer subtype. We found expected interactions but also discovered new relationships between drugs which might have implications for cancer treatment regimens.

A simple method to estimate the episode and programme sensitivity of breast cancer screening programmes.

Science.gov (United States)

Zorzi, Manuel; Guzzinati, Stefano; Puliti, Donella; Paci, Eugenio

2010-01-01

The estimation of breast cancer screening sensitivity is a major aim in the quality assessment of screening programmes. The proportional incidence method for the estimation of the sensitivity of breast cancer screening programmes is rarely used to estimate the underlying incidence rates. We present a method to estimate episode and programme sensitivity of screening programmes, based solely on cancers detected within screening cycles (excluding breast cancer cases at prevalent screening round) and on the number of incident cases in the total target population (steady state). The assumptions, strengths and limitations of the method are discussed. An example of calculation of episode and programme sensitivities is given, on the basis of the data from the IMPACT study, a large observational study of breast cancer screening programmes in Italy. The programme sensitivity from the fifth year of screening onwards ranged between 41% and 48% of the total number of cases in the target population. At steady state episode sensitivity was 0.70, with a trend across age groups, with lowest values in women aged 50-54 years (0.52) and highest in those 65-69 (0.77). The method is a very serviceable tool for estimating sensitivity in service screening programmes, and the results are comparable with those of other methods of estimation.

Imaging of human breast tissue using polarization sensitive optical coherence tomography

Science.gov (United States)

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

2011-12-01

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

Interfacial layers in tape cast anode-supported doped lanthanum gallate SOFC elements

Energy Technology Data Exchange (ETDEWEB)

Maffei, N.; De Silveira, G. [Materials Technology Laboratory, Natural Resources Canada, CANMET, 405 Rochester Street, Ottawa, Ontario (Canada) K1A OG3

2003-04-01

Lanthanum gallate doped with strontium and magnesium (LSGM) is a promising electrolyte system for intermediate temperature solid oxide fuel cells (SOFCs). The reported formation of interfacial layers in monolithic type SOFCs based on lanthanum gallate is of concern because of its impact on the performance of the fuel cell. Planar anode-supported SOFC elements (without the cathode) were prepared by the tape casting technique in order to determine the nature of the anode/electrolyte interface after sintering. Two anode systems were studied, one a NiO-CeO{sub 2} cermet, and the other, a modified lanthanum gallate anode containing manganese. Sintering studies were conducted at 1250, 1300, 1350, 1400 and 1450 C to determine the effect of temperature on the interfacial characteristics. Scanning electron microscopy (SEM) revealed a significant diffusion of Ni from the NiO-CeO{sub 2} anode resulting in the formation of an interfacial layer regardless of sintering temperature. Significant La diffusion from the electrolyte into the anode was also observed. In the case of the modified lanthanum gallate anode containing manganese, there was no interfacial layer formation, but a significant diffusion of Mn into the electrolyte was observed.

Molecular interactions between (--epigallocatechin gallate analogs and pancreatic lipase.

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Shihui Wang

Full Text Available The molecular interactions between pancreatic lipase (PL and four tea polyphenols (EGCG analogs, like (--epigallocatechin gallate (EGCG, (--gallocatechin gallate (GCG, (--epicatechin gallate (ECG, and (--epigallocatechin (EC, were studied from PL activity, conformation, kinetics and thermodynamics. It was observed that EGCG analogs inhibited PL activity, and their inhibitory rates decreased by the order of EGCG>GCG>ECG>EC. PL activity at first decreased rapidly and then slowly with the increase of EGCG analogs concentrations. α-Helix content of PL secondary structure decreased dependent on EGCG analogs concentration by the order of EGCG>GCG>ECG>EC. EGCG, ECG, and EC could quench PL fluorescence both dynamically and statically, while GCG only quenched statically. EGCG analogs would induce PL self-assembly into complexes and the hydrodynamic radii of the complexes possessed a close relationship with the inhibitory rates. Kinetics analysis showed that EGCG analogs non-competitively inhibited PL activity and did not bind to PL catalytic site. DSC measurement revealed that EGCG analogs decreased the transition midpoint temperature of PL enzyme, suggesting that these compounds reduced PL enzyme thermostability. In vitro renaturation through urea solution indicated that interactions between PL and EGCG analogs were weak and non-covalent.

21 CFR 184.1660 - Propyl gallate.

Science.gov (United States)

2010-04-01

... alcohol. (b) The ingredient meets the specifications of the “Food Chemicals Codex,” 3d Ed. (1981), pp. 257... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Propyl gallate. 184.1660 Section 184.1660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

Antibacterial activity of alkyl gallates is a combination of direct targeting of FtsZ and permeabilization of bacterial membranes

NARCIS (Netherlands)

Krol, Ewa; de Sousa Borges, Anabela; da Silva, Isabel; Polaquini, Carlos; Regasini, Luis; Ferreira, Henrique; Scheffers, Dirk

2015-01-01

Alkyl gallates are compounds with reported antibacterial activity. One of the modes of action is binding of the alkyl gallates to the bacterial membrane and interference with membrane integrity. However, alkyl gallates also cause cell elongation and disruption of cell division in the important plant

Epigallocatechin-3-gallate Promotes Osteoblastic Activity in Human ...

African Journals Online (AJOL)

Keywords: Epigallocatechin-3-gallate, Osteoporosis, Osteoclast, Proliferation, Estrogen receptor. Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (SciSearch), Scopus,. International Pharmaceutical Abstract, Chemical Abstracts, Embase, Index Copernicus, EBSCO, African. Index Medicus ...

Protective effect of (-)-epigallocatechin gallate on ultraviolet b ...

African Journals Online (AJOL)

Purpose: To investigate the protective effect of green tea (-)-epigallocatechin gallate (EGCg) on ultraviolet B (UV-B)-induced skin damages in hairless mice in order to develop a natural sunscreen ... hydrophilic cream has also showed high.

THE EFFECT OF GREEN TEA EXTRACT - EPIGALLOCATECHIN GALLATE (EGCG ON PORCINE OVARIAN GRANULOSA CELL

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Attila Kádasi

2014-02-01

Full Text Available The aim of our study was to elucidate the potential effect of green tea substance on basic ovarian functions. For this purpose, we examined the action of green tea bioactive molecule, epigallocatechin gallate (given at doses 0, 1, 10, 100 μg/mL, on cultured porcine ovarian granulosa cell functions - proliferation, apoptosis and steroidogenesis. Accumulation of PCNA (marker of proliferation, BAX (marker of apoptosis and the release of steroid hormones (progesterone and testosterone were analysed by immunocytochemistry and RIA respectively. It was observed that epigallocatechin gallate addition decreased the percentage of proliferative (PCNA-positive cells at all used doses (1, 10 and 100 μg/mL. The percentage of apoptotic (BAX-positive cells was increased at the highest used dose (100 μg/mL, but not a lower doses. Epigallocatechin gallate stimulated progesterone release (at 10 μg/mL but not at 1 and 100 μg/mL and diminished testosterone release (at 1 μg/mL but not at 10 and 100 μg/mL by porcine granulosa cells. Our results suggest a direct effect of epigallocatechin gallate on proliferation, apoptosis and steroidogenesis in porcine ovaries. Taken together, these data suggest that green tea molecule epigallocatechin gallate can negatively affect reproductive (ovarian functions – suppress ovarian cell proliferation, promote their apoptosis and alter release of steroid hormones.

Preventive effects of a major component of green tea, epigallocathechin-3-gallate, on hepatitis-B virus DNA replication.

Science.gov (United States)

Karamese, Murat; Aydogdu, Sabiha; Karamese, Selina Aksak; Altoparlak, Ulku; Gundogdu, Cemal

2015-01-01

Hepatitis B virus infection is one of the major world health problems. Epigallocatechin-3 gallate is the major component of the polyphenolic fraction of green tea and it has an anti-viral, anti-mutagenic, anti- tumorigenic, anti-angiogenic, anti-proliferative, and/or pro-apoptotic effects on mammalian cells. In this study, our aim was to investigate the inhibition of HBV replication by epigallocatechin-3 gallate in the Hep3B2.1-7 hepatocellular carcinoma cell line. HBV-replicating Hep3B2.1-7 cells were used to investigate the preventive effects of epigallocatechin-3 gallate on HBV DNA replication. The expression levels of HBsAg and HBeAg were determined using ELISA. Quantitative real-time-PCR was applied for the determination of the expression level of HBV DNA. Cytotoxicity of epigallocathechin-3-gallate was not observed in the hepatic carcinoma cell line when the dose was lower than 100 μM. The ELISA method demonstrated that epigallocatechin-3 gallate have strong effects on HBsAg and HBeAg levels. Also it was detected by real-time PCR that epigallocatechin-3 gallate could prevent HBV DNA replication. The obtained data pointed out that although the exact mechanism of HBV DNA replication and related diseases remains unclear, epigallocatechin-3 gallate has a potential as an effective anti-HBV agent with low toxicity.

Needle-based polarization-sensitive OCT of breast tumor (Conference Presentation)

Science.gov (United States)

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

2016-03-01

OCT imaging through miniature needle probes has extended the range of OCT and enabled structural imaging deep inside breast tissue, with the potential to assist in the intraoperative assessment of tumor margins. However, in many situations, scattering contrast alone is insufficient to clearly identify and delineate malignant areas. Here, we present a portable, depth-encoded polarization-sensitive OCT system, connected to a miniature needle probe. From the measured polarization states we constructed the tissue Mueller matrix at each sample location and improved the accuracy of the measured polarization states through incoherent averaging before retrieving the depth-resolved tissue birefringence. With the Mueller matrix at hand, additional polarization properties such as depolarization are readily available. We then imaged freshly excised breast tissue from a patient undergoing lumpectomy. The reconstructed local retardation highlighted regions of connective tissue, which exhibited birefringence due to the abundance of collagen fibers, and offered excellent contrast to areas of malignant tissue, which exhibited less birefringence due to their different tissue composition. Results were validated against co-located histology sections. The combination of needle-based imaging with the complementary contrast provided by polarization-sensitive analysis offers a powerful instrument for advanced tissue imaging and has potential to aid in the assessment of tumor margins during the resection of breast cancer.

MICROBIOLOGY AND SENSITIVITY PATTERN OF LACTATIONAL AND NON-LACTATIONAL BREAST ABSCESS IN SOUTHERN ODISHA

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Niranjan Sahoo

2017-10-01

Full Text Available BACKGROUND Breast abscess is one of the most frequently encountered cases in the General Surgery OPD among females. This fact can be supported by the fact that 4.6% and 11% of the women in developed and developing countries are affected by breast abscess. Breast abscesses are generally categorised as one of two types: Lactational abscesses and non-lactational abscesses. MATERIALS AND METHODS The present study was conducted from December 2015 to January 2017 on female patients visiting the General Surgery OPD of MKCG Medical College and Hospital with presumptive diagnosis of breast abscess. Both lactational and non-lactational females were included in the study. A total of 53 subjects with breast abscess were included in the study. The diagnosis of breast abscess was made from the clinical signs and symptoms of infection. Patients having any benign or malignant disease of breast were excluded from the study. RESULTS Of the 53 specimens found positive for bacterial yield, 43 were monomicrobial and only 10 were polymicrobial. Out of the 53 samples collected, only 6 showed anaerobic growth. Most common aerobic Gram positive isolate found in the sample was Staphylococcus aureus followed by Staphylococcus epidermidis. Most common aerobic Gram negative organism isolated was Pseudomonas aeruginosa found in 14 cases followed by Escherichia coli in 10 cases. Anaerobic bacteria were found only in nonlactational breast abscess. Of the anaerobic isolates, 5 are monomicrobial and 1 was polymicrobial. Aerobic Gram positive isolates showed sensitivity to most of the commonly used antibiotics. All the 4 gram negative isolates were found to be 100% sensitive to Piperacillin Tazobactam combination and Imipenem/Cilastatin combination. Pseudomonas was found to be somewhat resistant to Amikacin, Levofloxacin and Cephalosporins. Anaerobes were found to be fully sensitive to Metronidazole, Clindamycin and Piperacillin-Tazobactam combination. CONCLUSION Hence, this

ATM inhibition induces synthetic lethality and enhances sensitivity of PTEN-deficient breast cancer cells to cisplatin.

Science.gov (United States)

Li, Ke; Yan, Huaying; Guo, Wenhao; Tang, Mei; Zhao, Xinyu; Tong, Aiping; Peng, Yong; Li, Qintong; Yuan, Zhu

2018-05-01

PTEN deficiency often causes defects in DNA damage repair. Currently, effective therapies for breast cancer are lacking. ATM is an attractive target for cancer treatment. Previous studies suggested a synthetic lethality between PTEN and PARP. However, the synthetically lethal interaction between PTEN and ATM in breast cancer has not been reported. Moreover, the mechanism remains elusive. Here, using KU-60019, an ATM kinase inhibitor, we investigated ATM inhibition as a synthetically lethal strategy to target breast cancer cells with PTEN defects. We found that KU-60019 preferentially sensitizes PTEN-deficient MDA-MB-468 breast cancer cells to cisplatin, though it also slightly enhances sensitivity of PTEN wild-type breast cancer cells. The increased cytotoxic sensitivity is associated with apoptosis, as evidenced by flow cytometry and PARP cleavage. Additionally, the increase of DNA damage accumulation due to the decreased capability of DNA repair, as indicated by γ-H2AX and Rad51 foci, also contributed to this selective cytotoxicity. Mechanistically, compared with PTEN wild-type MDA-MB-231 cells, PTEN-deficient MDA-MB-468 cells have lower level of Rad51, higher ATM kinase activity, and display the elevated level of DNA damage. Moreover, these differences could be further enlarged by cisplatin. Our findings suggest that ATM is a promising target for PTEN-defective breast cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

Aquaglyceroporin-null trypanosomes display glycerol transport defects and respiratory-inhibitor sensitivity.

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Laura Jeacock

2017-03-01

Full Text Available Aquaglyceroporins (AQPs transport water and glycerol and play important roles in drug-uptake in pathogenic trypanosomatids. For example, AQP2 in the human-infectious African trypanosome, Trypanosoma brucei gambiense, is responsible for melarsoprol and pentamidine-uptake, and melarsoprol treatment-failure has been found to be due to AQP2-defects in these parasites. To further probe the roles of these transporters, we assembled a T. b. brucei strain lacking all three AQP-genes. Triple-null aqp1-2-3 T. b. brucei displayed only a very moderate growth defect in vitro, established infections in mice and recovered effectively from hypotonic-shock. The aqp1-2-3 trypanosomes did, however, display glycerol uptake and efflux defects. They failed to accumulate glycerol or to utilise glycerol as a carbon-source and displayed increased sensitivity to salicylhydroxamic acid (SHAM, octyl gallate or propyl gallate; these inhibitors of trypanosome alternative oxidase (TAO can increase intracellular glycerol to toxic levels. Notably, disruption of AQP2 alone generated cells with glycerol transport defects. Consistent with these findings, AQP2-defective, melarsoprol-resistant clinical isolates were sensitive to the TAO inhibitors, SHAM, propyl gallate and ascofuranone, relative to melarsoprol-sensitive reference strains. We conclude that African trypanosome AQPs are dispensable for viability and osmoregulation but they make important contributions to drug-uptake, glycerol-transport and respiratory-inhibitor sensitivity. We also discuss how the AQP-dependent inverse sensitivity to melarsoprol and respiratory inhibitors described here might be exploited.

Highly-sensitive and large-dynamic diffuse optical tomography system for breast tumor detection

Science.gov (United States)

Du, Wenwen; Zhang, Limin; Yin, Guoyan; Zhang, Yanqi; Zhao, Huijuan; Gao, Feng

2018-02-01

Diffuse optical tomography (DOT) as a new functional imaging has important clinical applications in many aspects such as benign and malignant breast tumor detection, tumor staging and so on. For quantitative detection of breast tumor, a three-wavelength continuous-wave DOT prototype system combined the ultra-high sensitivity of the photon-counting detection and the measurement parallelism of the lock-in technique was developed to provide high temporal resolution, high sensitivity, large dynamic detection range and signal-to-noise ratio. Additionally, a CT-analogous scanning mode was proposed to cost-effectively increase the detection data. To evaluate the feasibility of the system, a series of assessments were conducted. The results demonstrate that the system can obtain high linearity, stability and negligible inter-wavelength crosstalk. The preliminary phantom experiments show the absorption coefficient is able to be successfully reconstructed, indicating that the system is one of the ideal platforms for optical breast tumor detection.

Stabilization of antioxidant gallate in layered double hydroxide by exfoliation and reassembling reaction

Science.gov (United States)

Ansy, Kanakappan Mickel; Lee, Ji-Hee; Piao, Huiyan; Choi, Goeun; Choy, Jin-Ho

2018-06-01

As for the stabilization of chemically sensitive bioactive molecule in this study, gallic acid (GA) with antioxidant property was intercalated into interlayer space of layered double hydroxide (LDH), which was realized by exfoliation and reassembling reaction. At first, the pristine nitrate-type Zn2Al-LDH in solid state was synthesized via co-precipitation followed by the hydrothermal treatment at 80 °C for 6 h, and then exfoliated in formamide to form a colloidal solution of exfoliated LDH nanosheets, and finally reassembled in the presence of GA to prepare GA intercalated LDH (GA-LDH) desired, where the pH was adjusted to 8.0 in order to deprotonate GA to form gallate anion. According to the XRD analysis, GA-LDH showed well-developed (00l) diffraction peaks with a basal spacing of 1.15 nm, which was estimated to be larger than that of the pristine LDH (0.88 nm), indicating that gallate molecules were incorporated into LDH layers with perpendicular orientation. From the FT-IR spectra it was found that gallic acid was completely deprotonated into gallate, and stabilized in between LDH lattices via electrostatic interaction. The content of GA in GA-LDH was determined to be around 23 wt% by UV-vis spectroscopic study, which was also confirmed by HPLC analysis. According to the in-vitro release of GA out of GA-LDH in PBS solution (pH 7.4) at 4 °C, GA was sustainably released from GA-LDH nanohybrid up to 86% within 72 h. The antioxidant property of GA-LDH was almost the same with that of intact GA which was examined by DPPH. The photostability of GA-LDH under UV light irradiation was immensely enhanced compared to intact GA. It is, therefore, concluded that the present GA-LDH nanohybrid can be considered as an excellent antioxidant material with high chemical- and photo-stabilities, and controlled release property.

Order parameters in lanthanum gallate lightly doped with manganese and paramagnetic resonance

Science.gov (United States)

Vazhenin, V. A.; Potapov, A. P.; Artyomov, M. Yu.; Guseva, V. B.

2010-09-01

The Cr3+ centers have been revealed, transitions at room temperature have been identified, and spin Hamiltonian parameters have been determined for the Cr3+ and Fe3+ triclinic centers in lanthanum gallate lightly doped with manganese. The principal axes of the fourth-rank fine-structure tensor for the Fe3+ triclinic centers have been established and used to determine the order parameters, i.e., the angles of rotation of oxygen octahedra of lanthanum gallate with respect to the perovskite structure. The order parameter in the rhombohedral phase has been estimated.

Methyl Gallate Inhibits Osteoclast Formation and Function by Suppressing Akt and Btk-PLCγ2-Ca2+ Signaling and Prevents Lipopolysaccharide-Induced Bone Loss.

Science.gov (United States)

Baek, Jong Min; Kim, Ju-Young; Lee, Chang Hoon; Yoon, Kwon-Ha; Lee, Myeung Su

2017-03-07

In the field of bone research, various natural derivatives have emerged as candidates for osteoporosis treatment by targeting abnormally elevated osteoclastic activity. Methyl gallate, a plant-derived phenolic compound, is known to have numerous pharmacological effects against inflammation, oxidation, and cancer. Our purpose was to explore the relation between methyl gallate and bone metabolism. Herein, we performed screening using methyl gallate by tartrate resistant acid phosphatase (TRAP) staining and revealed intracellular mechanisms responsible for methyl gallate-mediated regulation of osteoclastogenesis by Western blotting and quantitative reverse transcription polymerase chain reaction (RT-PCR). Furthermore, we assessed the effects of methyl gallate on the characteristics of mature osteoclasts. We found that methyl gallate significantly suppressed osteoclast formation through Akt and Btk-PLCγ2-Ca 2+ signaling. The blockade of these pathways was confirmed through transduction of cells with a CA-Akt retrovirus and evaluation of Ca 2+ influx intensity (staining with Fluo-3/AM). Indeed, methyl gallate downregulated the formation of actin ring-positive osteoclasts and resorption pit areas. In agreement with in vitro results, we found that administration of methyl gallate restored osteoporotic phenotype stimulated by acute systemic injection of lipopolysaccharide in vivo according to micro-computed tomography and histological analysis. Our data strongly indicate that methyl gallate may be useful for the development of a plant-based antiosteoporotic agent.

Methyl Gallate Inhibits Osteoclast Formation and Function by Suppressing Akt and Btk-PLCγ2-Ca2+ Signaling and Prevents Lipopolysaccharide-Induced Bone Loss

Directory of Open Access Journals (Sweden)

Jong Min Baek

2017-03-01

Full Text Available In the field of bone research, various natural derivatives have emerged as candidates for osteoporosis treatment by targeting abnormally elevated osteoclastic activity. Methyl gallate, a plant-derived phenolic compound, is known to have numerous pharmacological effects against inflammation, oxidation, and cancer. Our purpose was to explore the relation between methyl gallate and bone metabolism. Herein, we performed screening using methyl gallate by tartrate resistant acid phosphatase (TRAP staining and revealed intracellular mechanisms responsible for methyl gallate-mediated regulation of osteoclastogenesis by Western blotting and quantitative reverse transcription polymerase chain reaction (RT-PCR. Furthermore, we assessed the effects of methyl gallate on the characteristics of mature osteoclasts. We found that methyl gallate significantly suppressed osteoclast formation through Akt and Btk-PLCγ2-Ca2+ signaling. The blockade of these pathways was confirmed through transduction of cells with a CA-Akt retrovirus and evaluation of Ca2+ influx intensity (staining with Fluo-3/AM. Indeed, methyl gallate downregulated the formation of actin ring-positive osteoclasts and resorption pit areas. In agreement with in vitro results, we found that administration of methyl gallate restored osteoporotic phenotype stimulated by acute systemic injection of lipopolysaccharide in vivo according to micro-computed tomography and histological analysis. Our data strongly indicate that methyl gallate may be useful for the development of a plant-based antiosteoporotic agent.

Novel targets for sensitizing breast cancer cells to TRAIL-induced apoptosis with siRNA delivery.

Science.gov (United States)

Thapa, Bindu; Bahadur Kc, Remant; Uludağ, Hasan

2018-02-01

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in variety of cancer cells without affecting most normal cells, which makes it a promising agent for cancer therapy. However, TRAIL therapy is clinically not effective due to resistance induction. To identify novel regulators of TRAIL that can aid in therapy, protein targets whose silencing sensitized breast cancer cells against TRAIL were screened with an siRNA library against 446 human apoptosis-related proteins in MDA-231 cells. Using a cationic lipopolymer (PEI-αLA) for delivery of library members, 16 siRNAs were identified that sensitized the TRAIL-induced death in MDA-231 cells. The siRNAs targeting BCL2L12 and SOD1 were further evaluated based on the novelty and their ability to sensitize TRAIL induced cell death. Silencing both targets sensitized TRAIL-mediated cell death in MDA-231 cells as well as TRAIL resistant breast cancer cells, MCF-7. Combination of TRAIL and siRNA silencing BCL2L12 had no effect in normal human umbilical vein cells and human bone marrow stromal cell. The silencing of BCL2L12 and SOD1 enhanced TRAIL-mediated apoptosis in MDA-231 cells via synergistically activating capsase-3 activity. Hence, here we report siRNAs targeting BCL2L12 and SOD1 as a novel regulator of TRAIL-induced cell death in breast cancer cells, providing a new approach for enhancing TRAIL therapy for breast cancer. The combination of siRNA targeting BCL2L12 and TRAIL can be a highly effective synergistic pair in breast cancer cells with minimal effect on the non-transformed cells. © 2017 UICC.

Epigallocatechin gallate ameliorates chronic fatigue syndrome in mice: behavioral and biochemical evidence.

Science.gov (United States)

Sachdeva, Anand Kamal; Kuhad, Anurag; Tiwari, Vinod; Chopra, Kanwaljit

2009-12-28

Three decades after the coining of the term chronic fatigue syndrome, the diagnosis of this illness is still symptom based and the aetiology remains elusive. Chronic fatigue syndrome pathogenesis seems to be multifactorial and the possible involvement of immune system is supported. The present study was designed to evaluate the effects of the epigallocatechin gallate in a mouse model of immunologically induced chronic fatigue. On 19th day, after lipopolysaccharide/Brucella abortus administration, the mice showed significant increase in immobility period, post swim fatigue and thermal hyperalgesia. Behavioral deficits were coupled with enhanced oxidative-nitrosative stress as evident by increased lipid peroxidation, nitrite levels and decreased endogenous antioxidant enzymes (superoxide dismutase, reduced glutathione and catalase) and inflammation (increased levels of tumor necrosis factor-alpha and tissue growth factor-beta). Chronic treatment with epigallocatechin gallate restored these behavioral and biochemical alterations in mice. The present study points out towards the beneficial effect of epigallocatechin gallate in the amelioration of chronic fatigue syndrome and thus may provide a new, effective and powerful strategy to treat chronic fatigue syndrome.

Analysis of the individual radio sensitivity of breast cancer patients; Untersuchungen zur individuellen Strahlenempfindlichkeit von Brustkrebspatientinnen

Energy Technology Data Exchange (ETDEWEB)

Auer, Judith

2013-04-04

Individual radiosensitivity has a crucial impact on radiotherapy related side effects. A prediction of individual radiosensitivity could avoid these side effects. Our aim was to study a breast cancer collective for its variation of individual radiosensitivity. Peripheral blood samples were obtained from 129 individuals. 67 breast cancer patients and 62 healthy and age matched individuals were looked at and their individual radiosensitivity was estimated by a 3-color Fluorescence in situ hybridization approach. Blood samples were obtained (i) before starting adjuvant radiotherapy and were in vitro irradiated by 2 Gy; (ii) after 5 single doses of 1.8 Gy and after 72 h had elapsed. DNA of lymphocytes was probed with whole chromosome painting for chromosomes 1, 2 and 4. The rate of breaks per metaphase was analyzed and used as a predictor of individual radiosensitivity. Breast cancer patients were distinctly more radio-sensitive compared to healthy controls. Additionally the distribution of the cancer patients' radiosensitivity was broader. A subgroup of 9 rather radio-sensitive and 9 rather radio-resistant patients was identified. A subgroup of patients aged between 40 and 50 was distinctly more radio-sensitive than younger or older patients. The in vivo irradiation approach was not applicable to detect individual radiosensitivity. In the breast cancer collective a distinctly resistant and sensitive subgroup is identified, which could be subject for treatment adjustment. Especially in the range of age 40 to 50 patients have an increased radiosensitivity. An in vivo irradiation in a breast cancer collective is not suitable to estimate individual radiosensitivity due to a low deposed dose.

The influence of propyl gallate and α-tocopherol on the survival time of rats during fasting

NARCIS (Netherlands)

Tonkelaar, E.M. den; Verschuuren, H.G.; Kroes, R.; Esch, G.J. van

1968-01-01

A toxicological investigation was carried out in order to repeat and extend the findings of Bukhman (Vop. Pitan. 1962, 21, 68) concerning the toxicity of propyl gallate in fasting rats. Rats were given a diet containing 0·002 or 0·004% propyl gallate or α-tocopherol. After 13 wk some of the animals

Y-27632 Increases Sensitivity of PANC-1 Cells to Epigallocatechin Gallate (EGCG) in Regulating Cell Proliferation and Migration

Science.gov (United States)

Liu, Xing; Bi, Yongyi

2016-01-01

Background The study aimed to investigate the inhibitory effect of (1R,4r)-4-((R)-1-aminoethyl)-N-(pyridin-4-yl) cyclohexanecarboxamide (Y-27632) and (−)-epigallocatechin-3-gallate (EGCG) on the proliferation and migration of PANC-1 cells. EGCG, found in green tea, has been previously shown to be one of the most abundant and powerful catechins in cancer prevention and treatment. Y-27632, a selective inhibitor of rho-associated protein kinase 1, is widely used in treating cardiovascular disease, inflammation, and cancer. Material/Methods PANC-1 cells, maintained in Dulbecco’s Modified Eagle’s Medium, were treated with dimethyl sulfoxide (control) as well as different concentrations (20, 40, 60, and 80 μg/mL) of EGCG for 48 h. In addition, PANC-1 cells were treated separately with 60 μg/mL EGCG, 20 μM Y-27632, and EGCG combined with Y-27632 (60 μg/mL EGCG + 20 μM Y-27632) for 48 h. The effect of EGCG and Y-27632 on the proliferation and migration of PANC-1 cells was evaluated using Cell Counting Kit-8 and transwell migration assays. The expression of peroxisome proliferator–activated receptor alpha (PPARα) and Caspase-3 mRNA was determined by Quantitative real-time polymerase chain reaction (RT-qPCR). Results EGCG (20–80 μg/mL) inhibited cell viability in a dose-dependent manner. Y-27632 enhanced the sensitivity of PANC-1 cells to EGCG (by increasing the expression of PPARα and Caspase-3 mRNA) and suppressed cell proliferation. PANC-1 cell migration was inhibited by treatment with a combination of EGCG and Y-27632. Conclusions Y-27632 increases the sensitivity of PANC-1 cells to EGCG in regulating cell proliferation and migration, which is likely to be related to the expression of PPARα mRNA and Caspase-3 mRNA. PMID:27694793

Sensitivity of CA 15-3, CEA and serum HER2 in the early detection of recurrence of breast cancer

DEFF Research Database (Denmark)

Eriksen, Ann Christina; Sørensen, Patricia Diana; Jacobsen, Erik Hugger

2013-01-01

The aim of this project was to investigate the sensitivity of CA 15-3, CEA and HER2 in the early diagnosis of metastatic breast cancer.......The aim of this project was to investigate the sensitivity of CA 15-3, CEA and HER2 in the early diagnosis of metastatic breast cancer....

The role of cone-beam breast-CT for breast cancer detection relative to breast density.

Science.gov (United States)

Wienbeck, Susanne; Uhlig, Johannes; Luftner-Nagel, Susanne; Zapf, Antonia; Surov, Alexey; von Fintel, Eva; Stahnke, Vera; Lotz, Joachim; Fischer, Uwe

2017-12-01

To evaluate the impact of breast density on the diagnostic accuracy of non-contrast cone-beam breast computed tomography (CBBCT) in comparison to mammography for the detection of breast masses. A retrospective study was conducted from August 2015 to July 2016. Fifty-nine patients (65 breasts, 112 lesions) with BI-RADS, 5th edition 4 or 5 assessment in mammography and/or ultrasound of the breast received an additional non-contrast CBBCT. Independent double blind reading by two radiologists was performed for mammography and CBBCT imaging. Sensitivity, specificity and AUC were compared between the modalities. Breast lesions were histologically examined in 85 of 112 lesions (76%). The overall sensitivity for CBBCT (reader 1: 91%, reader 2: 88%) was higher than in mammography (both: 68%, pdensity group (pdensity breasts. • Overall sensitivity for non-contrast CBBCT ranged between 88%-91%. • Sensitivity was higher for CBBCT than mammography in both density types (pdensity types (pdensity types (p<0.001).

Transdermal solid delivery of epigallocatechin-3-gallate using self-double-emulsifying drug delivery system as vehicle: Formulation, evaluation and vesicle-skin interaction.

Science.gov (United States)

Hu, Caibiao; Gu, Chengyu; Fang, Qiao; Wang, Qiang; Xia, Qiang

2016-02-01

The present study investigated a self-double-emulsifying drug delivery system loaded with epigallocatechin-3-gallate to improve epigallocatechin-3-gallate skin retention. The long chain solid lipids (cetostearyl alcohol) and macadamia oil were utilized as a carrier to deliver the bioactive ingredient. Response surface methodology was used to optimize the formulation, and the solid lipid to total lipid weight ratio, concentration of epigallocatechin-3-gallate and hydrophilic surfactant on skin retention were found to be the principal factors. The optimum formulation with high encapsulation efficiency (95.75%), self-double-emulsification performance (99.58%) and skin retention (87.24%) were derived from the fitted models and experimentally examined, demonstrating a reasonable agreement between experimental and predicted values. Epigallocatechin-3-gallate-self-double-emulsifying drug delivery system was found to be stable for 3 months. Transdermal studies could explain a higher skin diffusion of epigallocatechin-3-gallate from the self-double-emulsifying drug delivery system compared with EGCG aqueous solution. In vitro cytotoxicity showed that epigallocatechin-3-gallate-self-double-emulsifying drug delivery system did not exert hazardous effect on L929 cells up to 1:10. © The Author(s) 2015.

Exosome derived from epigallocatechin gallate treated breast cancer cells suppresses tumor growth by inhibiting tumor-associated macrophage infiltration and M2 polarization

International Nuclear Information System (INIS)

Jang, Ji-Young; Lee, Jong-Kuen; Jeon, Yoon-Kyung; Kim, Chul-Woo

2013-01-01

Tumor-associated macrophages (TAM) play an important role in tumor microenvironment. Particularly, M2 macrophages contribute to tumor progression, depending on the expression of NF-κB. Tumor-derived exosomes can modulate tumor microenvironment by transferring miRNAs to immune cells. Epigallocatechin gallate (EGCG) has well known anti-tumor effects; however, no data are available on the influence of EGCG on communication with cancer cells and TAM. Murine breast cancer cell lines, 4T1, was used for in vivo and ex vivo studies. Exosome was extracted from EGCG-treated 4T1 cells, and the change of miRNAs was screened using microarray. Tumor cells or TAM isolated from murine tumor graft were incubated with exosomes derived from EGCG-treated and/or miR-16 inhibitor-transfected 4T1 cells. Chemokines for monocytes (CSF-1 and CCL-2), cytokines both with high (IL-6 and TGF-β) and low (TNF-α) expression in M2 macrophages, and molecules in NF-κB pathway (IKKα and Iκ-B) were evaluated by RT-qPCR or western blot. EGCG suppressed tumor growth in murine breast cancer model, which was associated with decreased TAM and M2 macrophage infiltration. Expression of chemokine for monocytes (CSF-1 and CCL-2) were low in tumor cells from EGCG-treated mice, and cytokines of TAM was skewed from M2- into M1-like phenotype by EGCG as evidenced by decreased IL-6 and TGF-β and increased TNF-α. Ex vivo incubation of isolated tumor cells with EGCG inhibited the CSF-1 and CCL-2 expression. Ex vivo incubation of TAM with exosomes from EGCG-treated 4T1 cells led to IKKα suppression and concomitant I-κB accumulation; increase of IL-6 and TGF-β; and, decrease of TNF-α. EGCG up-regulated miR-16 in 4T1 cells and in the exosomes. Treatment of tumor cells or TAM with exosomes derived from EGCG-treated and miR-16-knock-downed 4T1 cells restored the above effects on chemokines, cytokines, and NF-κB pathway elicited by EGCG-treated exosomes. Our data demonstrate that EGCG up-regulates miR-16 in

Contrast-enhanced breast MRI: factors affecting sensitivity and specificity

Energy Technology Data Exchange (ETDEWEB)

Piccoli, C.W. [Department of Radiology, Jefferson Medical College, Thomas Jefferson University Hospital, 132 South 10th Street, 7th floor, Philadelphia, PA 19107-5244 (United States)

1997-12-31

Contrast-enhanced MRI (CE-MRI) of the breast has been investigated for over 10 years. The reports of sensitivity for cancer detection have generally been greater than 90 %. However, estimates of specificity have varied greatly. Differing results are due to differences in study populations, technical methods and criteria for interpretation. Early and marked signal rise, detected using dynamic imaging technique following contrast administration, is the MRI hallmark of cancer. However, some malignant lesions may enhance slowly or minimally, and a variety of benign lesions may enhance rapidly with marked signal intensity. High resolution techniques generally requiring longer acquisition times are more likely to depict the slowly enhancing malignancies at the cost of a decrease in specificity due to lack of temporal resolution. This disadvantage may be offset by the improved visualization of lesion morphology with high resolution images. This report reviews the methods and results of the leading investigators of breast MRI. (orig.) With 3 figs., 70 refs.

Contrast-enhanced breast MRI: factors affecting sensitivity and specificity

International Nuclear Information System (INIS)

Piccoli, C.W.

1997-01-01

Contrast-enhanced MRI (CE-MRI) of the breast has been investigated for over 10 years. The reports of sensitivity for cancer detection have generally been greater than 90 %. However, estimates of specificity have varied greatly. Differing results are due to differences in study populations, technical methods and criteria for interpretation. Early and marked signal rise, detected using dynamic imaging technique following contrast administration, is the MRI hallmark of cancer. However, some malignant lesions may enhance slowly or minimally, and a variety of benign lesions may enhance rapidly with marked signal intensity. High resolution techniques generally requiring longer acquisition times are more likely to depict the slowly enhancing malignancies at the cost of a decrease in specificity due to lack of temporal resolution. This disadvantage may be offset by the improved visualization of lesion morphology with high resolution images. This report reviews the methods and results of the leading investigators of breast MRI. (orig.)

The expression level of HJURP has an independent prognostic impact and predicts the sensitivity to radiotherapy in breast cancer

International Nuclear Information System (INIS)

Hu, Zhi; Huang, Ge; Sadanandam, Anguraj; Gu, Shenda; Lenburg, Marc E.; Pai, Melody; Bayani, Nora; Blakely, Eleanor A.; Gray, Joe W.; Mao, Jian-Hua

2010-01-01

HJURP (Holliday Junction Recognition Protein) is a newly discovered gene reported to function at centromeres and to interact with CENPA. However its role in tumor development remains largely unknown. The goal of this study was to investigate the clinical significance of HJURP in breast cancer and its correlation with radiotherapeutic outcome. We measured HJURP expression level in human breast cancer cell lines and primary breast cancers by Western blot and/or by Affymetrix Microarray; and determined its associations with clinical variables using standard statistical methods. Validation was performed with the use of published microarray data. We assessed cell growth and apoptosis of breast cancer cells after radiation using high-content image analysis. HJURP was expressed at higher level in breast cancer than in normal breast tissue. HJURP mRNA levels were significantly associated with estrogen receptor (ER), progesterone receptor (PR), Scarff-Bloom-Richardson (SBR) grade, age and Ki67 proliferation indices, but not with pathologic stage, ERBB2, tumor size, or lymph node status. Higher HJURP mRNA levels significantly decreased disease-free and overall survival. HJURP mRNA levels predicted the prognosis better than Ki67 proliferation indices. In a multivariate Cox proportional-hazard regression, including clinical variables as covariates, HJURP mRNA levels remained an independent prognostic factor for disease-free and overall survival. In addition HJURP mRNA levels were an independent prognostic factor over molecular subtypes (normal like, luminal, Erbb2 and basal). Poor clinical outcomes among patients with high HJURP expression were validated in five additional breast cancer cohorts. Furthermore, the patients with high HJURP levels were much more sensitive to radiotherapy. In vitro studies in breast cancer cell lines showed that cells with high HJURP levels were more sensitive to radiation treatment and had a higher rate of apoptosis than those with low levels

The expression level of HJURP has an independent prognostic impact and predicts the sensitivity to radiotherapy in breast cancer

Energy Technology Data Exchange (ETDEWEB)

Hu, Zhi; Huang, Ge; Sadanandam, Anguraj; Gu, Shenda; Lenburg, Marc E; Pai, Melody; Bayani, Nora; Blakely, Eleanor A; Gray, Joe W; Mao, Jian-Hua

2010-06-25

Introduction: HJURP (Holliday Junction Recognition Protein) is a newly discovered gene reported to function at centromeres and to interact with CENPA. However its role in tumor development remains largely unknown. The goal of this study was to investigate the clinical significance of HJURP in breast cancer and its correlation with radiotherapeutic outcome. Methods: We measured HJURP expression level in human breast cancer cell lines and primary breast cancers by Western blot and/or by Affymetrix Microarray; and determined its associations with clinical variables using standard statistical methods. Validation was performed with the use of published microarray data. We assessed cell growth and apoptosis of breast cancer cells after radiation using high-content image analysis. Results: HJURP was expressed at higher level in breast cancer than in normal breast tissue. HJURP mRNA levels were significantly associated with estrogen receptor (ER), progesterone receptor (PR), Scarff-Bloom-Richardson (SBR) grade, age and Ki67 proliferation indices, but not with pathologic stage, ERBB2, tumor size, or lymph node status. Higher HJURP mRNA levels significantly decreased disease-free and overall survival. HJURP mRNA levels predicted the prognosis better than Ki67 proliferation indices. In a multivariate Cox proportional-hazard regression, including clinical variables as covariates, HJURP mRNA levels remained an independent prognostic factor for disease-free and overall survival. In addition HJURP mRNA levels were an independent prognostic factor over molecular subtypes (normal like, luminal, Erbb2 and basal). Poor clinical outcomes among patients with high HJURP expression werevalidated in five additional breast cancer cohorts. Furthermore, the patients with high HJURP levels were much more sensitive to radiotherapy. In vitro studies in breast cancer cell lines showed that cells with high HJURP levels were more sensitive to radiation treatment and had a higher rate of apoptosis

Combined epigallocatechin-3-gallate and resveratrol supplementation for 12 wk increases mitochondrial capacity and fat oxidation, but not insulin sensitivity, in obese humans: a randomized controlled trial

NARCIS (Netherlands)

Most, Jasper; Timmers, S.; Warnke, I.; Jocken, J.J.W.; Boekschoten, M.V.; Groot, de Philip; Bendik, Igor; Schrauwen, Patrick; Goossens, Gijs H.; Blaak, Ellen E.

2016-01-01

Background: The obese insulin-resistant state is characterized by
impairments in lipid metabolism.We previously showed that 3-d supplementation
of combined epigallocatechin-3-gallate and resveratrol
(EGCG+RES) increased energy expenditure and improved the
capacity to switch from fat

Increased cellular uptake of lauryl gallate loaded in superparamagnetic poly(methyl methacrylate) nanoparticles due to surface modification with folic acid.

Science.gov (United States)

Feuser, Paulo Emilio; Arévalo, Juan Marcelo Carpio; Junior, Enio Lima; Rossi, Gustavo Rodrigues; da Silva Trindade, Edvaldo; Rocha, Maria Eliane Merlin; Jacques, Amanda Virtuoso; Ricci-Júnior, Eduardo; Santos-Silva, Maria Claudia; Sayer, Claudia; de Araújo, Pedro H Hermes

2016-12-01

Lauryl gallate loaded in superparamagnetic poly(methyl methacrylate) nanoparticles surface modified with folic acid were synthesized by miniemulsion polymerization in just one step. In vitro biocompatibility and cytotoxicity assays on L929 (murine fibroblast), human red blood, and HeLa (uterine colon cancer) cells were performed. The effect of folic acid at the nanoparticles surface was evaluated through cellular uptake assays in HeLa cells. Results showed that the presence of folic acid did not affect substantially the polymer particle size (~120 nm), the superparamagnetic behavior, the encapsulation efficiency of lauryl gallate (~87 %), the Zeta potential (~38 mV) of the polymeric nanoparticles or the release profile of lauryl gallate. The release profile of lauryl gallate from superparamagnetic poly(methyl methacrylate) nanoparticles presented an initial burst effect (0-1 h) followed by a slow and sustained release, indicating a biphasic release system. Lauryl gallate loaded in superparamagnetic poly(methyl methacrylate) nanoparticles with folic acid did not present cytotoxicity effects on L929 and human red blood cells. However, free lauryl gallate presented significant cytotoxic effects on L929 and human red blood cells at all tested concentrations. The presence of folic acid increased the cytotoxicity of lauryl gallate loaded in nanoparticles on HeLa cells due to a higher cellular uptake when HeLa cells were incubated at 37 °C. On the other hand, when the nanoparticles were incubated at low temperature (4 °C) cellular uptake was not observed, suggesting that the uptake occurred by folate receptor mediated energy-dependent endocytosis. Based on presented results our work suggests that this carrier system can be an excellent alternative in targeted drug delivery by folate receptor.

Epigallocatechin-3-Gallate Protects Erythrocyte Ca2+-ATPase and Na+/K+-ATPase Against Oxidative Induced Damage During Aging in Humans

Directory of Open Access Journals (Sweden)

Prabhanshu Kumar

2014-10-01

Full Text Available Purpose: The main purpose of this study was to investigate the protective role of epigallocatechin-3-gallate on tertiary butyl hydroperoxide induced oxidative damage in erythrocyte during aging in humans. Methods: Human erythrocyte membrane bound Ca2+-ATPase and Na+/K+-ATPase activities were determined as a function of human age. Protective role of epigallocatechin-3-gallate was evaluated by in vitro experiments by adding epigallocatechin-3-gallate in concentration dependent manner (final concentration range 10-7M to 10-4M to the enzyme assay medium. Oxidative stress was induced in vitro by incubating washed erythrocyte ghosts with tertiary butyl hydroperoxide (10-5 M final concentration. Results: We have reported concentration dependent effect of epigallocatechin-3-gallate on tertiary butyl hydroperoxide induced damage on activities of Ca2+-ATPase and Na+/K+-ATPase during aging in humans. We have detected a significant (p < 0.001 decreased activity of Ca2+-ATPase and Na+/K+ -ATPase as a function of human age. Epigallocatechin-3-gallate protected ATPases against tertiary butyl hydroperoxide induced damage in concentration dependent manner during aging in humans. Conclusion: Epigallocatechin-3-gallate is a powerful antioxidant that is capable of protecting erythrocyte Ca2+-ATPase and Na+/K+ -ATPase against oxidative stress during aging in humans. We may propose hypothesis that a high intake of catechin rich diet may provide some protection against development of aging and age related diseases.

Prediction of oxidation parameters of purified Kilka fish oil including gallic acid and methyl gallate by adaptive neuro-fuzzy inference system (ANFIS) and artificial neural network.

Science.gov (United States)

Asnaashari, Maryam; Farhoosh, Reza; Farahmandfar, Reza

2016-10-01

As a result of concerns regarding possible health hazards of synthetic antioxidants, gallic acid and methyl gallate may be introduced as natural antioxidants to improve oxidative stability of marine oil. Since conventional modelling could not predict the oxidative parameters precisely, artificial neural network (ANN) and neuro-fuzzy inference system (ANFIS) modelling with three inputs, including type of antioxidant (gallic acid and methyl gallate), temperature (35, 45 and 55 °C) and concentration (0, 200, 400, 800 and 1600 mg L(-1) ) and four outputs containing induction period (IP), slope of initial stage of oxidation curve (k1 ) and slope of propagation stage of oxidation curve (k2 ) and peroxide value at the IP (PVIP ) were performed to predict the oxidation parameters of Kilka oil triacylglycerols and were compared to multiple linear regression (MLR). The results showed ANFIS was the best model with high coefficient of determination (R(2)  = 0.99, 0.99, 0.92 and 0.77 for IP, k1 , k2 and PVIP , respectively). So, the RMSE and MAE values for IP were 7.49 and 4.92 in ANFIS model. However, they were to be 15.95 and 10.88 and 34.14 and 3.60 for the best MLP structure and MLR, respectively. So, MLR showed the minimum accuracy among the constructed models. Sensitivity analysis based on the ANFIS model suggested a high sensitivity of oxidation parameters, particularly the induction period on concentrations of gallic acid and methyl gallate due to their high antioxidant activity to retard oil oxidation and enhanced Kilka oil shelf life. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Epigallocatechin-3-gallate suppresses the expression of HSP70 and HSP90 and exhibits anti-tumor activity in vitro and in vivo

International Nuclear Information System (INIS)

Tran, Phan LCHB; Kim, Soo-A; Choi, Hong Seok; Yoon, Jung-Hoon; Ahn, Sang-Gun

2010-01-01

Epigallocatechin-3-gallate (EGCG), one of the major catechins in green tea, is a potential chemopreventive agent for various cancers. The aim of this study was to examine the effect of EGCG on the expression of heat shock proteins (HSPs) and tumor suppression. Cell colony formation was evaluated by a soft agar assay. Transcriptional activity of HSP70 and HSP90 was determined by luciferase reporter assay. An EGCG-HSPs complex was prepared using EGCG attached to the cyanogen bromide (CNBr)-activated Sepharose 4B. In vivo effect of EGCG on tumor growth was examined in a xenograft model. Treatment with EGCG decreased cell proliferation and colony formation of MCF-7 human breast cancer cells. EGCG specifically inhibited the expression of HSP70 and HSP90 by inhibiting the promoter activity of HSP70 and HSP90. Pretreatment with EGCG increased the stress sensitivity of MCF-7 cells upon heat shock (44°C for 1 h) or oxidative stress (H 2 O 2 , 500 μM for 24 h). Moreover, treatment with EGCG (10 mg/kg) in a xenograft model resulted in delayed tumor incidence and reduced tumor size, as well as the inhibition of HSP70 and HSP90 expression. Overall, these findings demonstrate that HSP70 and HSP90 are potent molecular targets of EGCG and suggest EGCG as a drug candidate for the treatment of human cancer

MiR-33a Decreases High-Density Lipoprotein-Induced Radiation Sensitivity in Breast Cancer

Energy Technology Data Exchange (ETDEWEB)

Wolfe, Adam R.; Bambhroliya, Arvind [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Reddy, Jay P. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Debeb, Bisrat G. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Huo, Lei [Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Larson, Richard; Li, Li [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Ueno, Naoto T. [Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Woodward, Wendy A., E-mail: wwoodward@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2016-06-01

Purpose: We previously showed that high-density lipoprotein (HDL) radiosensitizes inflammatory breast cancer (IBC) cells in vitro and is associated with better local control after radiation therapy in IBC patients. The microRNA miR-33 family negatively regulates the adenosine triphosphate binding cassette transporter subfamily A member 1. We hypothesized that variations in miR-33a expression in IBC cancer cells versus non-IBC cells would correlate with radiation sensitivity following exposure to HDL in vitro. Methods and Materials: MiR-33a expression was analyzed by reverse transcriptase–polymerase chain reaction in 4 cell lines representing common clinical breast cancer subtypes. Overexpression and knockdown of miR-33a was demonstrated via transfection of an miR-33a mimic or an anti-miR-33a construct in high- and low-expressing miR-33a cell lines. Clonogenic survival in vitro in these cells was quantified at baseline and following HDL treatment. MiR-33a expression on distant relapse-free survival (DRFS) of 210 cases downloaded from the Oxford breast cancer dataset was determined. Results: Expression levels of miR-33a were lower in IBC cell lines and IBC tumor samples than in non-IBC cell lines and normal breast tissue. Cholesterol concentrations in the cell membranes were higher in IBC cells than in non-IBC cells. Clonogenic survival following 24 hours of HDL treatment was decreased in response to irradiation in the low-miR-33a–expressing cell lines SUM149 and KPL4, but survival following HDL treatment decreased in the high-miR-33a–expressing cell lines MDA-MB-231 and SUM159. In the high-miR-33a–expressing cell lines, anti-miR-33a transfection decreased radiation resistance in clonogenic assays. Conversely, in the low-miR-33a–expressing cell lines, the miR-33a mimic reversed the HDL-induced radiation sensitization. Breast cancer patients in the top quartile based on miR-33a expression had markedly lower rates of DRFS than the bottom quartile (P

MiR-33a Decreases High-Density Lipoprotein-Induced Radiation Sensitivity in Breast Cancer

International Nuclear Information System (INIS)

Wolfe, Adam R.; Bambhroliya, Arvind; Reddy, Jay P.; Debeb, Bisrat G.; Huo, Lei; Larson, Richard; Li, Li; Ueno, Naoto T.; Woodward, Wendy A.

2016-01-01

Purpose: We previously showed that high-density lipoprotein (HDL) radiosensitizes inflammatory breast cancer (IBC) cells in vitro and is associated with better local control after radiation therapy in IBC patients. The microRNA miR-33 family negatively regulates the adenosine triphosphate binding cassette transporter subfamily A member 1. We hypothesized that variations in miR-33a expression in IBC cancer cells versus non-IBC cells would correlate with radiation sensitivity following exposure to HDL in vitro. Methods and Materials: MiR-33a expression was analyzed by reverse transcriptase–polymerase chain reaction in 4 cell lines representing common clinical breast cancer subtypes. Overexpression and knockdown of miR-33a was demonstrated via transfection of an miR-33a mimic or an anti-miR-33a construct in high- and low-expressing miR-33a cell lines. Clonogenic survival in vitro in these cells was quantified at baseline and following HDL treatment. MiR-33a expression on distant relapse-free survival (DRFS) of 210 cases downloaded from the Oxford breast cancer dataset was determined. Results: Expression levels of miR-33a were lower in IBC cell lines and IBC tumor samples than in non-IBC cell lines and normal breast tissue. Cholesterol concentrations in the cell membranes were higher in IBC cells than in non-IBC cells. Clonogenic survival following 24 hours of HDL treatment was decreased in response to irradiation in the low-miR-33a–expressing cell lines SUM149 and KPL4, but survival following HDL treatment decreased in the high-miR-33a–expressing cell lines MDA-MB-231 and SUM159. In the high-miR-33a–expressing cell lines, anti-miR-33a transfection decreased radiation resistance in clonogenic assays. Conversely, in the low-miR-33a–expressing cell lines, the miR-33a mimic reversed the HDL-induced radiation sensitization. Breast cancer patients in the top quartile based on miR-33a expression had markedly lower rates of DRFS than the bottom quartile (P

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

DEFF Research Database (Denmark)

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

1985-01-01

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

Identification of breast cancer cell subtypes sensitive to ATG4B inhibition.

Science.gov (United States)

Bortnik, Svetlana; Choutka, Courtney; Horlings, Hugo M; Leung, Samuel; Baker, Jennifer H; Lebovitz, Chandra; Dragowska, Wieslawa H; Go, Nancy E; Bally, Marcel B; Minchinton, Andrew I; Gelmon, Karen A; Gorski, Sharon M

2016-10-11

Autophagy, a lysosome-mediated degradation and recycling process, functions in advanced malignancies to promote cancer cell survival and contribute to cancer progression and drug resistance. While various autophagy inhibition strategies are under investigation for cancer treatment, corresponding patient selection criteria for these autophagy inhibitors need to be developed. Due to its central roles in the autophagy process, the cysteine protease ATG4B is one of the autophagy proteins being pursued as a potential therapeutic target. In this study, we investigated the expression of ATG4B in breast cancer, a heterogeneous disease comprised of several molecular subtypes. We examined a panel of breast cancer cell lines, xenograft tumors, and breast cancer patient specimens for the protein expression of ATG4B, and found a positive association between HER2 and ATG4B protein expression. We showed that HER2-positive cells, but not HER2-negative breast cancer cells, require ATG4B to survive under stress. In HER2-positive cells, cytoprotective autophagy was dependent on ATG4B under both starvation and HER2 inhibition conditions. Combined knockdown of ATG4B and HER2 by siRNA resulted in a significant decrease in cell viability, and the combination of ATG4B knockdown with trastuzumab resulted in a greater reduction in cell viability compared to trastuzumab treatment alone, in both trastuzumab-sensitive and -resistant HER2 overexpressing breast cancer cells. Together these results demonstrate a novel association of ATG4B positive expression with HER2 positive breast cancers and indicate that this subtype is suitable for emerging ATG4B inhibition strategies.

Breast-feeding does not protect against allergic sensitization in early childhood and allergy-associated disease at age 7 years

DEFF Research Database (Denmark)

Jelding-Dannemand, Ea; Malby Schoos, Ann-Marie; Bisgaard, Hans

2015-01-01

clinic at 7 years of age, strictly adhering to predefined algorithms. Associations between duration of exclusive breast-feeding and outcomes were analyzed by logistic regression. RESULTS: We found no significant association between duration of exclusive breast-feeding and development of sensitization......% CI, 0.82-1.14]; and OR, 1.02 [95% CI, 0.84-1.23], respectively). Adjusting for reverse causation by excluding children with eczema, wheeze, or a positive skin prick test response before ending exclusive breast-feeding did not alter the results. CONCLUSION: Exclusive breast-feeding does not affect...

The role of cone-beam breast-CT for breast cancer detection relative to breast density

Energy Technology Data Exchange (ETDEWEB)

Wienbeck, Susanne; Uhlig, Johannes; Fintel, Eva von; Stahnke, Vera; Lotz, Joachim [University Medical Center Goettingen, Institute for Diagnostic and Interventional Radiology, Goettingen (Germany); Luftner-Nagel, Susanne; Fischer, Uwe [Diagnostic Breast Center Goettingen, Goettingen (Germany); Zapf, Antonia [University Medical Center Goettingen, Department of Medical Statistics, Goettingen (Germany); Surov, Alexey [University of Leipzig, Department of Diagnostic and Interventional Radiology, Leipzig (Germany)

2017-12-15

To evaluate the impact of breast density on the diagnostic accuracy of non-contrast cone-beam breast computed tomography (CBBCT) in comparison to mammography for the detection of breast masses. A retrospective study was conducted from August 2015 to July 2016. Fifty-nine patients (65 breasts, 112 lesions) with BI-RADS, 5th edition 4 or 5 assessment in mammography and/or ultrasound of the breast received an additional non-contrast CBBCT. Independent double blind reading by two radiologists was performed for mammography and CBBCT imaging. Sensitivity, specificity and AUC were compared between the modalities. Breast lesions were histologically examined in 85 of 112 lesions (76%). The overall sensitivity for CBBCT (reader 1: 91%, reader 2: 88%) was higher than in mammography (both: 68%, p<0.001), and also for the high-density group (p<0.05). The specificity and AUC was higher for mammography in comparison to CBBCT (p<0.05 and p<0.001). The interobserver agreement (ICC) between the readers was 90% (95% CI: 86-93%) for mammography and 87% (95% CI: 82-91%) for CBBCT. Compared with two-view mammography, non-contrast CBBCT has higher sensitivity, lower specificity, and lower AUC for breast mass detection in both high and low density breasts. (orig.)

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

Directory of Open Access Journals (Sweden)

Meagan B. Myers

2016-04-01

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

Antioxidant activity of gallic acid and methyl gallate in triacylglycerols of Kilka fish oil and its oil-in-water emulsion.

Science.gov (United States)

Asnaashari, Maryam; Farhoosh, Reza; Sharif, Ali

2014-09-15

The anti-DPPH radical effect as well as anti-peroxide activity of gallic acid, methyl gallate, and α-tocopherol in a bulk Kilka fish oil and its oil-in-water emulsion stabilized by soy protein isolate at 55°C were investigated. Gallic acid with the lowest hydrophobicity (log P=-0.28) was found to be the most active antiradical agent (IC50=29.5 μM), followed by methyl gallate (IC50=38.0 μM, log P=-0.23) and α-tocopherol (IC50=105.3 μM, log P=0.70). The anti-peroxide activity in the bulk oil system decreased in the order of methyl gallate>gallic acid>α-tocopherol. In the emulsion system, methyl gallate still behaved better than gallic acid, but the highest activity belonged to α-tocopherol. Based on the calculation of a number of kinetic parameters, the antioxidants, in general, showed better performances in the bulk oil system than in the emulsion system. Copyright © 2014 Elsevier Ltd. All rights reserved.

Development of a 1 kW Class SOFC Stack using Doped Lanthanum Gallate

Energy Technology Data Exchange (ETDEWEB)

Akikusa, J.; Adachi, K.; Yamada, T.; Akbay, T.; Murakami, N.; Chitose, N.; Hoshino, K.; Hosoi, K.; Yoshida, H.; Sasaki, T.; Inagaki, T.; Ishihara, T.; Takita, Y.

2002-06-01

The performance of lanthanum gallate based SOFC has been investigated as a high-energy conversion device. A planar type SOFC which could operate at temperatures below 800 {sup o}C has been jointly developed. As an electrolyte material, lanthanum gallate (LaGaO{sub 3}) with substitutions of Sr for the La site and Mg and Co for the Ga site (LSGMC) was used. The synthesis technique for large-sized cell production has been established, and the performance of a self- supported diameter 154 mm cell with 200 {mu}m electrolyte thickness is investigated. The output power of 50 W has been obtained with a conversion efficiency [LHV] of 45 % for a single cell. In addition, a metallic separator made of stainless steel was chosen and tested successfully for a seal-less stack. The output power of 1 kW by means of the stack of 18 cells has been achieved for the first time utilizing lanthanum gallate. Moreover, NiO-SDC composite powders were prepared by the spray pyrolysis method and used for the anode on 100 {mu}m thickness LSGMC electrolyte with a combination of samarium cobaltite for the cathode. The power density of as high as 1.8 W/cm{sup 2} at 0.7 V terminal voltage was achieved at 800{sup o}C. (author)

Breast MRI, digital mammography and breast tomosynthesis: comparison of three methods for early detection of breast cancer.

Science.gov (United States)

Roganovic, Dragana; Djilas, Dragana; Vujnovic, Sasa; Pavic, Dag; Stojanov, Dragan

2015-11-16

Breast cancer is the most common malignancy in women and early detection is important for its successful treatment. The aim of this study was to investigate the sensitivity and specificity of three methods for early detection of breast cancer: breast magnetic resonance imaging (MRI), digital mammography, and breast tomosynthesis in comparison to histopathology, as well as to investigate the intraindividual variability between these modalities. We included 57 breast lesions, each detected by three diagnostic modalities: digital mammography, breast MRI, and breast tomosynthesis, and subsequently confirmed by histopathology. Breast Imaging-Reporting and Data System (BI-RADS) was used for characterizing the lesions. One experienced radiologist interpreted all three diagnostic modalities. Twenty-nine of the breast lesions were malignant while 28 were benign. The sensitivity for digital mammography, breast MRI, and breast tomosynthesis, was 72.4%, 93.1%, and 100%, respectively; while the specificity was 46.4%, 60.7%, and 75%, respectively. Receiver operating characteristics (ROC) curve analysis showed an overall diagnostic advantage of breast tomosynthesis over both breast MRI and digital mammography. The difference in performance between breast tomosynthesis and digital mammography was significant (p tomosynthesis and breast MRI was not significant (p=0.20).

A targeted enzyme approach to sensitization of tyrosine kinase inhibitor-resistant breast cancer cells.

Science.gov (United States)

Giordano, Courtney R; Mueller, Kelly L; Terlecky, Laura J; Krentz, Kendra A; Bollig-Fischer, Aliccia; Terlecky, Stanley R; Boerner, Julie L

2012-10-01

Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) of potential use in patients with breast cancer. Unfortunately, in clinical studies, gefitinib is often ineffective indicating that resistance to EGFR inhibitors may be a common occurrence in cancer of the breast. EGFR has been shown to be overexpressed in breast cancer, and in particular remains hyperphosphorylated in cell lines such as MDA-MB-468 that are resistant to EGFR inhibitors. Here, we investigate the cause of this sustained phosphorylation and the molecular basis for the ineffectiveness of gefitinib. We show that reactive oxygen species (ROS), known to damage cellular macromolecules and to modulate signaling cascades in a variety of human diseases including cancers, appear to play a critical role in mediating EGFR TKI-resistance. Furthermore, elimination of these ROS through use of a cell-penetrating catalase derivative sensitizes the cells to gefitinib. These results suggest a new approach for the treatment of TKI-resistant breast cancer patients specifically, the targeting of ROS and attendant downstream oxidative stress and their effects on signaling cascades. Copyright © 2012. Published by Elsevier Inc.

Widespread molecular patterns associated with drug sensitivity in breast cancer cell lines, with implications for human tumors.

Directory of Open Access Journals (Sweden)

Chad J Creighton

Full Text Available BACKGROUND: Recent landmark studies have profiled cancer cell lines for molecular features, along with measuring the corresponding growth inhibitory effects for specific drug compounds. These data present a tool for determining which subsets of human cancer might be more responsive to particular drugs. To this end, the NCI-DREAM-sponsored DREAM7: Drug Sensitivity Prediction Challenge (sub-challenge 1 set out to predict the sensitivities of 18 breast cancer cell lines to 31 previously untested compounds, on the basis of molecular profiling data and a training subset of cell lines. METHODS AND RESULTS: With 47 teams submitting blinded predictions, team Creighton scored third in terms of overall accuracy. Team Creighton's method was simple and straightforward, incorporated multiple expression data types (RNA-seq, gene array, RPPA, and incorporated all profiled features (not only the "best" predictive ones. As an extension of the approach, cell line data, from public datasets of expression profiling coupled with drug sensitivities (Barretina, Garnett, Heiser were used to "predict" the drug sensitivities in human breast tumors (using data from The Cancer Genome Atlas. Drug sensitivity correlations within human breast tumors showed differences by expression-based subtype, with many associations in line with the expected (e.g. Lapatinib sensitivity in HER2-enriched cancers and others inviting further study (e.g. relative resistance to PI3K inhibitors in basal-like cancers. CONCLUSIONS: Molecular patterns associated with drug sensitivity are widespread, with potentially hundreds of genes that could be incorporated into making predictions, as well as offering biological clues as to the mechanisms involved. Applying the cell line patterns to human tumor data may help generate hypotheses on what tumor subsets might be more responsive to therapies, where multiple cell line datasets representing various drugs may be used, in order to assess consistency of

Volumetric breast density measurement: sensitivity analysis of a relative physics approach.

Science.gov (United States)

Lau, Susie; Ng, Kwan Hoong; Abdul Aziz, Yang Faridah

2016-10-01

To investigate the sensitivity and robustness of a volumetric breast density (VBD) measurement system to errors in the imaging physics parameters including compressed breast thickness (CBT), tube voltage (kVp), filter thickness, tube current-exposure time product (mAs), detector gain, detector offset and image noise. 3317 raw digital mammograms were processed with Volpara(®) (Matakina Technology Ltd, Wellington, New Zealand) to obtain fibroglandular tissue volume (FGV), breast volume (BV) and VBD. Errors in parameters including CBT, kVp, filter thickness and mAs were simulated by varying them in the Digital Imaging and Communications in Medicine (DICOM) tags of the images up to ±10% of the original values. Errors in detector gain and offset were simulated by varying them in the Volpara configuration file up to ±10% from their default values. For image noise, Gaussian noise was generated and introduced into the original images. Errors in filter thickness, mAs, detector gain and offset had limited effects on FGV, BV and VBD. Significant effects in VBD were observed when CBT, kVp, detector offset and image noise were varied (p applications such as tracking density change over time, it remains to be seen how accurate the measures need to be.

Radiogenic male breast cancer with in vitro sensitivity to ionizing radiation and bleomycin

International Nuclear Information System (INIS)

Greene, M.H.; Goedert, J.J.; Bech-Hansen, N.T.; McGuire, D.; Paterson, M.C.; Fraumeni, J.F. Jr.

1983-01-01

A cytogenetically normal man with gynecomastia and a family history of diverse cancers developed adenocarcinoma of the breast 30 years following thymic irradiation. In vitro experiments measuring colony-forming ability of cultured skin fibroblasts from family members implied that the patient had a small but significant increase in sensitivity to ionizing radiation, and a moderate increase in sensitivity to bleomycin, a radiomimetic drug. Enhanced radiosensitivity of fibroblasts from the patient's mother, and bleomycin sensitivity of fibroblasts from the sister suggested, but did not prove, that genetic susceptibility affected the risk of radiogenic cancer in this individual. In vitro studies of cancer-prone kindreds are a useful research strategy in delineating mechanisms of carcinogenesis

Breast MRI, digital mammography and breast tomosynthesis: comparison of three methods for early detection of breast cancer

Directory of Open Access Journals (Sweden)

Dragana Roganovic

2015-11-01

Full Text Available Breast cancer is the most common malignancy in women and early detection is important for its successful treatment. The aim of this study was to investigate the sensitivity and specificity of three methods for early detection of breast cancer: breast magnetic resonance imaging (MRI, digital mammography, and breast tomosynthesis in comparison to histopathology, as well as to investigate the intraindividual variability between these modalities.  We included 57 breast lesions, each detected by three diagnostic modalities: digital mammography, breast MRI, and breast tomosynthesis, and subsequently confirmed by histopathology. Breast Imaging-Reporting and Data System (BI-RADS was used for characterizing the lesions. One experienced radiologist interpreted all three diagnostic modalities. Twenty-nine of the breast lesions were malignant while 28 were benign. The sensitivity for digital mammography, breast MRI, and breast tomosynthesis, was 72.4%, 93.1%, and 100%, respectively; while the specificity was 46.4%, 60.7%, and 75%, respectively. Receiver operating characteristics (ROC curve analysis showed an overall diagnostic advantage of breast tomosynthesis over both breast MRI and digital mammography. The difference in performance between breast tomosynthesis and digital mammography was significant (p < 0.001, while the difference between breast tomosynthesis and breast MRI was not significant (p = 0.20. 

Usefulness of breast-specific gamma imaging as an adjunct modality in breast cancer patients with dense breast. A comparative study with MRI

International Nuclear Information System (INIS)

Kim, Bom Sahn

2012-01-01

The aim of this study was to evaluate the adjunctive benefits of breast-specific gamma imaging (BSGI) versus magnetic resonance imaging (MRI) in breast cancer patients with dense breasts. This study included a total of 66 patients (44.1±8.2 years) with dense breasts (breast density >50%) and already biopsy-confirmed breast cancer. All of the patients underwent BSGI and MRI as part of an adjunct modality before the initial therapy. Of 66 patients, the 97 undetermined breast lesions were newly detected and correlated with the biopsy results. Twenty-six of the 97 breast lesions proved to be malignant tumors (invasive ductal cancer, n=16; ductal carcinoma in situ, n=6; mixed or other malignancies, n=4); the remaining 71 lesions were diagnosed as benign tumors. The sensitivity and specificity of BSGI were 88.8% (confidence interval (CI), 69.8-97.6%) and 90.1% (CI, 80.7-95.9%), respectively, while the sensitivity and specificity of MRI were 92.3% (CI, 74.9-99.1%) and 39.4% (CI, 28.0-51.7%), respectively (p<0.0001). MRI detected 43 false-positive breast lesions, 37 (86.0%) of which were correctly diagnosed as benign lesions using BSGI. In 12 malignant lesions <1 cm, the sensitivities of BSGI and MR imaging were 83.3% (CI, 51.6-97.9%) and 91.7% (CI, 61.5-99.8%), respectively. BSGI showed an equivocal sensitivity and a high specificity compared to MRI in the diagnosis of breast lesions. In addition, BSGI had a good sensitivity in discriminating breast cancers ≤1 cm. The results of this study suggest that BSGI could play a crucial role as an adjunctive imaging modality which can be used to evaluate breast cancer patients with dense breasts. (author)

Paramagnetic resonance of Mn4+ and Mn2+ centers in lanthanum gallate single crystals

Science.gov (United States)

Vazhenin, V. A.; Potapov, A. P.; Guseva, V. B.; Artyomov, M. Yu.

2010-03-01

An increase in the manganese concentration in lanthanum gallate in the range 0.5-5.0% has been found to result in a complete replacement of individual Mn4+ ions by Mn2+ ions. The relative concentrations and binding energies of individual Mn4+, Mn3+, and Mn2+ ions have been determined. The spin Hamiltonians of the Mn2+ and Mn4+ centers in the rhombohedral and orthorhombic phases, respectively, have been constructed and the orientation of the principal axes of the fine-structure tensor of Mn4+ at room temperature has been found. The possibility of using electron paramagnetic resonance for determining the rotation angles of oxygen octahedra of lanthanum gallate with respect to the perovskite structure has been discussed.

Palmitate-induced ER stress increases trastuzumab sensitivity in HER2/neu-positive breast cancer cells

International Nuclear Information System (INIS)

Baumann, Jan; Wong, Jason; Sun, Yan; Conklin, Douglas S.

2016-01-01

CHOP-dependent apoptosis as well as a partial activation of the ER stress response network via XBP1 and ATF6. This response appears to be a general feature of HER2/neu-positive breast cancer cells but not cells that overexpress only HER2/neu. Exogenous palmitate reduces HER2 and HER3 protein levels without changes in phosphorylation and sensitizes HER2/neu-positive breast cancer cells to treatment with the HER2-targeted therapy trastuzumab. Several studies have shown that HER2, FASN and fatty acid synthesis are functionally linked. Exogenous palmitate exerts its toxic effects in part through inducing ER stress, reducing HER2 expression and thereby sensitizing cells to trastuzumab. These data provide further evidence that HER2 signaling and fatty acid metabolism are highly integrated processes that may be important for disease development and progression. The online version of this article (doi:10.1186/s12885-016-2611-8) contains supplementary material, which is available to authorized users

Surveillance mammography for detecting ipsilateral breast tumour recurrence and metachronous contralateral breast cancer: a systematic review

Energy Technology Data Exchange (ETDEWEB)

Robertson, Clare; Boachie, Charles; Fraser, Cynthia; MacLennan, Graeme; Mowatt, Graham; Thomas, Ruth E. [University of Aberdeen, Health Services Research Unit, Aberdeen (United Kingdom); Ragupathy, Senthil Kumar Arcot [NHS Grampian, Radiology Department, Aberdeen Royal Infirmary, Aberdeen (United Kingdom); Heys, Steve D. [University of Aberdeen and Aberdeen Royal Infirmary, NHS Grampian, Division of Applied Medicine, School of Medicine and Dentistry, Aberdeen (United Kingdom); Gilbert, Fiona J. [University of Aberdeen and Aberdeen Royal Infirmary, NHS Grampian, Aberdeen Biomedical Imaging Centre, Aberdeen (United Kingdom)

2011-12-15

To determine the diagnostic accuracy of surveillance mammography for detecting ipsilateral breast tumour recurrence and metachronous contralateral breast cancer in women previously treated for primary breast cancer. A systematic review of surveillance mammography compared with ultrasound, magnetic resonance imaging (MRI), specialist-led clinical examination or unstructured primary care follow-up, using histopathological assessment for test positives and follow-up for test negatives as the reference standard. Nine studies met our inclusion criteria. Variations in study comparisons precluded meta-analysis. For routine ipsilateral breast tumour detection, surveillance mammography sensitivity ranged from 64-67% and specificity ranged from 85-97%. For MRI, sensitivity ranged from 86-100% and specificity was 93%. For non-routine ipsilateral breast tumour detection, sensitivity and specificity for surveillance mammography ranged from 50-83% and 57-75% and for MRI 93-100% and 88-96%. For routine metachronous contralateral breast cancer detection, one study reported sensitivity of 67% and specificity of 50% for both surveillance mammography and MRI. Although mammography is associated with high sensitivity and specificity, MRI is the most accurate test for detecting ipsilateral breast tumour recurrence and metachronous contralateral breast cancer in women previously treated for primary breast cancer. Results should be interpreted with caution because of the limited evidence base. (orig.)

WE-FG-BRA-11: Theranostic Platinum Nanoparticle for Radiation Sensitization in Breast Cancer Radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Yue, Y; Wagner, S; Medina-Kauwe, L; Cui, X; Zhang, G; Shiao, S; Sandler, H; Fraass, B [Cedars Sinai Medical Center, Los Angeles, CA (United States)

2016-06-15

Purpose: We have developed a novel receptor-targeted theranostic platinum nanoparticle (HER-PtNP) for enhanced radiation sensitization in HER2-positive breast cancer radiation treatment. This study aims to evaluate receptor-targeting specificity, and radiation sensitization of the nanoparticle. Methods: The platinum nanoparticle (PtNP) was synthesized with the diameter of 2nm, and capped with cysteine. The nanoparticle was tagged with a fluorescent dye (cy5) for the fluoresence detection, and conjuated with HER2/3 targeted protein (HerPBK10) for HER2-targeting specificity. We evaluated the theranostic features using in vitro breast cancer cell models: HER2-positive BT-474, and HER2-negative MDA-MB-231. The HER2-targeting specificity was evaluated using immunofluorescence and confocal microscopy. For each cell line, three sets of samples, including non-stained control, fluorescence stained PtNP-cy5 treated, and HER-PtNP treated, were imaged by confocal microscopy. Two breast cancer cell lineages were incubated with PtNP and HER-PtNP at 10 µg/mL, and then irradiated with X-rays for 2 Gy dose at 50 kVp. A colonogenic assay was used to determine cellular survival fractions by immediately reseeding 300 cells after irradiation in growth media and allowing colonies to grow for 2 weeks. Results: The results of confocal images show that no apparent nanoparticle cellular uptake was observed in the HER2-(MDA-MB-231) cells with 1% for PtNP-cy5 and 0.5% for HER-PtNP. Similarly no apparent PtNP-cy5 uptake (<1%) for BT474 cells was observed. However, there was significant HER-PtNP uptake (73%) for the HER2+(BT474) cells. The clonogenic assay showed that BT474 cells treated with HER-PtNP had significantly lower survival compared to those treated with PtNP (32% vs 81%, p=0.01). However, no significant radiosensitivity enhancement was observed for MDA-MB-231 cell treated with PtNP and HER-PtNP (89% vs 92%, p=0.78). Conclusion: Our studies suggest that the HER2-targeted platinum

WE-FG-BRA-11: Theranostic Platinum Nanoparticle for Radiation Sensitization in Breast Cancer Radiotherapy

International Nuclear Information System (INIS)

Yue, Y; Wagner, S; Medina-Kauwe, L; Cui, X; Zhang, G; Shiao, S; Sandler, H; Fraass, B

2016-01-01

Purpose: We have developed a novel receptor-targeted theranostic platinum nanoparticle (HER-PtNP) for enhanced radiation sensitization in HER2-positive breast cancer radiation treatment. This study aims to evaluate receptor-targeting specificity, and radiation sensitization of the nanoparticle. Methods: The platinum nanoparticle (PtNP) was synthesized with the diameter of 2nm, and capped with cysteine. The nanoparticle was tagged with a fluorescent dye (cy5) for the fluoresence detection, and conjuated with HER2/3 targeted protein (HerPBK10) for HER2-targeting specificity. We evaluated the theranostic features using in vitro breast cancer cell models: HER2-positive BT-474, and HER2-negative MDA-MB-231. The HER2-targeting specificity was evaluated using immunofluorescence and confocal microscopy. For each cell line, three sets of samples, including non-stained control, fluorescence stained PtNP-cy5 treated, and HER-PtNP treated, were imaged by confocal microscopy. Two breast cancer cell lineages were incubated with PtNP and HER-PtNP at 10 µg/mL, and then irradiated with X-rays for 2 Gy dose at 50 kVp. A colonogenic assay was used to determine cellular survival fractions by immediately reseeding 300 cells after irradiation in growth media and allowing colonies to grow for 2 weeks. Results: The results of confocal images show that no apparent nanoparticle cellular uptake was observed in the HER2-(MDA-MB-231) cells with 1% for PtNP-cy5 and 0.5% for HER-PtNP. Similarly no apparent PtNP-cy5 uptake (<1%) for BT474 cells was observed. However, there was significant HER-PtNP uptake (73%) for the HER2+(BT474) cells. The clonogenic assay showed that BT474 cells treated with HER-PtNP had significantly lower survival compared to those treated with PtNP (32% vs 81%, p=0.01). However, no significant radiosensitivity enhancement was observed for MDA-MB-231 cell treated with PtNP and HER-PtNP (89% vs 92%, p=0.78). Conclusion: Our studies suggest that the HER2-targeted platinum

Mammography combined with breast dynamic contrast-enhanced-magnetic resonance imaging for the diagnosis of early breast cancer

Institute of Scientific and Technical Information of China (English)

Yakun He; Guohui Xu; Jin Ren; Bin Feng; Xiaolei Dong; Hao Lu; Changjiu He

2016-01-01

Objective The aim of this study was to investigate the application of mammography combined with breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the diagnosis of early breast cancer. Methods Mammography and DCE-MRI were performed for 120 patients with breast cancer (malignant, 102; benign; 18). Results The sensitivity of mammography for early diagnosis of breast cancer was 66.67%, specificity was 77.78%, and accuracy was 68.33%. The sensitivity of MRI for early diagnosis of breast cancer was 94.12%, specificity was 88.89%, and accuracy was 93.33%. However, the sensitivity of mammography combined with DCE-MRI volume imaging with enhanced water signal (VIEWS) scanning for early diagnosis of breast cancer was 97.06%, specificity was 94.44%, and accuracy was 96.67%. Conclusion Mammography combined with DCE-MRI increased the sensitivity, specificity, and accuracy of diagnosing early breast cancer.

Inhibition of PKM2 sensitizes triple-negative breast cancer cells to doxorubicin

Energy Technology Data Exchange (ETDEWEB)

Wang, Feng [Department of Gastroenterology, The Tenth People’s Hospital of Shanghai, Tongji University, Shanghai 200072 (China); Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Yang, Yong, E-mail: yyang@houstonmethodist.org [Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Department of Medicine, Weill Cornell Medical College, New York, NY 10065 (United States)

2014-11-21

Highlights: • Suppression of PKM2 sensitizes triple-negative breast cancer cells to doxorubicin. • Repression of PKM2 affects the glycolysis and decreases ATP production. • Downregulation of PKM2 increases the intracellular accumulation of doxorubicin. • Inhibition of PKM2 enhances the antitumor efficacy of doxorubicin in vivo. - Abstract: Cancer cells alter regular metabolic pathways in order to sustain rapid proliferation. One example of metabolic remodeling in cancerous tissue is the upregulation of pyruvate kinase isoenzyme M2 (PKM2), which is involved in aerobic glycolysis. Indeed, PKM2 has previously been identified as a tumor biomarker and as a potential target for cancer therapy. Here, we examined the effects of combined treatment with doxorubicin and anti-PKM2 small interfering RNA (siRNA) on triple-negative breast cancer (TNBC). The suppression of PKM2 resulted in changes in glucose metabolism, leading to decreased synthesis of adenosine triphosphate (ATP). Reduced levels of ATP resulted in the intracellular accumulation of doxorubicin, consequently enhancing the therapeutic efficacy of this drug in several triple-negative breast cancer cell lines. Furthermore, the combined effect of PKM2 siRNA and doxorubicin was evaluated in an in vivo MDA-MB-231 orthotopic breast cancer model. The siRNA was systemically administered through a polyethylenimine (PEI)-based delivery system that has been extensively used. We demonstrate that the combination treatment showed superior anticancer efficacy as compared to doxorubicin alone. These findings suggest that targeting PKM2 can increase the efficacy of chemotherapy, potentially providing a new approach for improving the outcome of chemotherapy in patients with TNBC.

Computerized detection of breast cancer on automated breast ultrasound imaging of women with dense breasts

International Nuclear Information System (INIS)

Drukker, Karen; Sennett, Charlene A.; Giger, Maryellen L.

2014-01-01

Purpose: Develop a computer-aided detection method and investigate its feasibility for detection of breast cancer in automated 3D ultrasound images of women with dense breasts. Methods: The HIPAA compliant study involved a dataset of volumetric ultrasound image data, “views,” acquired with an automated U-Systems Somo•V ® ABUS system for 185 asymptomatic women with dense breasts (BI-RADS Composition/Density 3 or 4). For each patient, three whole-breast views (3D image volumes) per breast were acquired. A total of 52 patients had breast cancer (61 cancers), diagnosed through any follow-up at most 365 days after the original screening mammogram. Thirty-one of these patients (32 cancers) had a screening-mammogram with a clinically assigned BI-RADS Assessment Category 1 or 2, i.e., were mammographically negative. All software used for analysis was developed in-house and involved 3 steps: (1) detection of initial tumor candidates, (2) characterization of candidates, and (3) elimination of false-positive candidates. Performance was assessed by calculating the cancer detection sensitivity as a function of the number of “marks” (detections) per view. Results: At a single mark per view, i.e., six marks per patient, the median detection sensitivity by cancer was 50.0% (16/32) ± 6% for patients with a screening mammogram-assigned BI-RADS category 1 or 2—similar to radiologists’ performance sensitivity (49.9%) for this dataset from a prior reader study—and 45.9% (28/61) ± 4% for all patients. Conclusions: Promising detection sensitivity was obtained for the computer on a 3D ultrasound dataset of women with dense breasts at a rate of false-positive detections that may be acceptable for clinical implementation

Value of breast MRI as supplement to mammography and sonography for high risk breast cancer patients

International Nuclear Information System (INIS)

Schlossbauer, T.; Hellerhoff, K.; Reiser, M.

2008-01-01

The aim of this study is to give an overview on early detection of breast cancer in patients with an increased risk of breast cancer. Sensitivities and diagnostic accuracies of breast MRI, mammography and ultrasound were compared. A systematic literature search of the past 3 years was performed. Studies which compared breast imaging modalities and used image-guided biopsy results as standard of reference were included. Patients included had to have had an increased lifetime risk for breast cancer (>15%). Regarding sensitivity and diagnostic accuracy, breast MRI performed best in comparison to the other modalities within this collective of patients. Sensitivities ranged from 71-100%, 0-78%, and 13-65%, for MRI, mammography, and ultrasound, respectively Breast MRI is a well established tool for screening in patients at high risk for developing breast cancer and is a valuable supplement to mammography and ultrasound within this selected cohort of patients. (orig.) [de

Local structure of gallate proton conductors

International Nuclear Information System (INIS)

Giannici, F; Messana, D; Martorana, A; Longo, A; Sciortino, L

2009-01-01

Lanthanum barium gallate proton conductors are based on disconnected GaO 4 groups. The insertion of hydroxyls in the LaBaGaO 4 network proceeds through self-doping with Ba 2+ , consequent O 2- vacancy formation to fulfill charge neutrality. With a structural investigation on self-doped LaBaGaO 4 oxides using synchrotron XRD and EXAFS on the Ga K-edge, we find that: (a) the GaO 4 tetrahedra retain their size throughout the whole series; (b) the GaO 4 tetrahedra rotate as rigid bodies on hydration, leading to the formation of a network of shorter O-O configurations that are stabilized by hydrogen bonds; (c) contraction of the lattice occurs along the a unit cell axis, as a consequence of an overall structural rearrangement of the hydrated solid.

Local structure of gallate proton conductors

Science.gov (United States)

Giannici, F.; Messana, D.; Longo, A.; Sciortino, L.; Martorana, A.

2009-11-01

Lanthanum barium gallate proton conductors are based on disconnected GaO4 groups. The insertion of hydroxyls in the LaBaGaO4 network proceeds through self-doping with Ba2+, consequent O2- vacancy formation to fulfill charge neutrality. With a structural investigation on self-doped LaBaGaO4 oxides using synchrotron XRD and EXAFS on the Ga K-edge, we find that: (a) the GaO4 tetrahedra retain their size throughout the whole series; (b) the GaO4 tetrahedra rotate as rigid bodies on hydration, leading to the formation of a network of shorter O-O configurations that are stabilized by hydrogen bonds; (c) contraction of the lattice occurs along the a unit cell axis, as a consequence of an overall structural rearrangement of the hydrated solid.

Correlation of the radioprotective effect of the methyl gallate on the ruptures induction in DNA and it effect in the capture of free radicals

International Nuclear Information System (INIS)

Morales R, P.; Cabral P, A.; Cruz V, V.L.; Gonzalez B, F.; Zarco M, A.

2007-01-01

It is shown in alive, the capacity of the methyl gallate to reduce the induced ruptures in the DNA for γ radiation. As well as to capture free radicals in a system in vitro. This suggests that the methyl gallate can be a radioprotector that acts capturing free radicals. (Author)

Breast cancer screening in Korean woman with dense breast tissue

International Nuclear Information System (INIS)

Shin, Hee Jung; Ko, Eun Sook; Yi, Ann

2015-01-01

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

Breast cancer screening in Korean woman with dense breast tissue

Energy Technology Data Exchange (ETDEWEB)

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

2015-11-15

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

The Green Tea Component (--Epigallocatechin-3-Gallate Sensitizes Primary Endothelial Cells to Arsenite-Induced Apoptosis by Decreasing c-Jun N-Terminal Kinase-Mediated Catalase Activity.

Directory of Open Access Journals (Sweden)

Jee-Youn Kim

Full Text Available The green tea component (--epigallocatechin-3-gallate (EGCG has been shown to sensitize many different types of cancer cells to anticancer drug-induced apoptosis, although it protects against non-cancerous primary cells against toxicity from certain conditions such as exposure to arsenic (As or ultraviolet irradiation. Here, we found that EGCG promotes As-induced toxicity of primary-cultured bovine aortic endothelial cells (BAEC at doses in which treatment with each chemical alone had no such effect. Increased cell toxicity was accompanied by an increased condensed chromatin pattern and fragmented nuclei, cleaved poly(ADP-ribose polymerase (PARP, activity of the pro-apoptotic enzymes caspases 3, 8 and 9, and Bax translocation into mitochondria, suggesting the involvement of an apoptotic signaling pathway. Fluorescence activated cell sorting analysis revealed that compared with EGCG or As alone, combined EGCG and As (EGCG/As treatment significantly induced production of reactive oxygen species (ROS, which was accompanied by decreased catalase activity and increased lipid peroxidation. Pretreatment with N-acetyl-L-cysteine or catalase reversed EGCG/As-induced caspase activation and EC toxicity. EGCG/As also increased the phosphorylation of c-Jun N-terminal kinase (JNK, which was not reversed by catalase. However, pretreatment with the JNK inhibitor SP600125 reversed all of the observed effects of EGCG/As, suggesting that JNK may be the most upstream protein examined in this study. Finally, we also found that all the observed effects by EGCG/As are true for other types of EC tested. In conclusion, this is firstly to show that EGCG sensitizes non-cancerous EC to As-induced toxicity through ROS-mediated apoptosis, which was attributed at least in part to a JNK-activated decrease in catalase activity.

The Green Tea Component (-)-Epigallocatechin-3-Gallate Sensitizes Primary Endothelial Cells to Arsenite-Induced Apoptosis by Decreasing c-Jun N-Terminal Kinase-Mediated Catalase Activity.

Science.gov (United States)

Kim, Jee-Youn; Choi, Ji-Young; Lee, Hyeon-Ju; Byun, Catherine Jeonghae; Park, Jung-Hyun; Park, Jae Hoon; Cho, Ho-Seong; Cho, Sung-Jin; Jo, Sangmee Ahn; Jo, Inho

2015-01-01

The green tea component (-)-epigallocatechin-3-gallate (EGCG) has been shown to sensitize many different types of cancer cells to anticancer drug-induced apoptosis, although it protects against non-cancerous primary cells against toxicity from certain conditions such as exposure to arsenic (As) or ultraviolet irradiation. Here, we found that EGCG promotes As-induced toxicity of primary-cultured bovine aortic endothelial cells (BAEC) at doses in which treatment with each chemical alone had no such effect. Increased cell toxicity was accompanied by an increased condensed chromatin pattern and fragmented nuclei, cleaved poly(ADP-ribose) polymerase (PARP), activity of the pro-apoptotic enzymes caspases 3, 8 and 9, and Bax translocation into mitochondria, suggesting the involvement of an apoptotic signaling pathway. Fluorescence activated cell sorting analysis revealed that compared with EGCG or As alone, combined EGCG and As (EGCG/As) treatment significantly induced production of reactive oxygen species (ROS), which was accompanied by decreased catalase activity and increased lipid peroxidation. Pretreatment with N-acetyl-L-cysteine or catalase reversed EGCG/As-induced caspase activation and EC toxicity. EGCG/As also increased the phosphorylation of c-Jun N-terminal kinase (JNK), which was not reversed by catalase. However, pretreatment with the JNK inhibitor SP600125 reversed all of the observed effects of EGCG/As, suggesting that JNK may be the most upstream protein examined in this study. Finally, we also found that all the observed effects by EGCG/As are true for other types of EC tested. In conclusion, this is firstly to show that EGCG sensitizes non-cancerous EC to As-induced toxicity through ROS-mediated apoptosis, which was attributed at least in part to a JNK-activated decrease in catalase activity.

Technical Note: Robust measurement of the slice-sensitivity profile in breast tomosynthesis

Energy Technology Data Exchange (ETDEWEB)

Maki, Aili K., E-mail: aili.maki@sri.utoronto.ca; Mainprize, James G. [Physical Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5 (Canada); Yaffe, Martin J. [Departments of Medical Imaging and Medical Biophysics, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada and Physical Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5 (Canada)

2016-08-15

Purpose: The purpose of this work is to improve the repeatability of the measurement of the slice-sensitivity profile (SSP) in reconstructed breast tomosynthesis volumes. Methods: A grid of aluminum ball-bearings (BBs) within a PMMA phantom was imaged on breast tomosynthesis systems from three different manufacturers. The full-width half-maximum (FWHM) values were measured for the SSPs of the BBs in the reconstructed volumes. The effect of transforming the volumes from a Cartesian coordinate system (CCS) to a cone-beam coordinate system (CBCS) on the variability in the FWHM values was assessed. Results: Transforming the volumes from a CCS to a CBCS before measuring the SSPs reduced the coefficient of variation (COV) in the measurements of FWHM in repeated measurements by 56% and reduced the dependence of the FWHM values on the location of the BBs within the reconstructed volume by 76%. Conclusions: Measuring the SSP in the volumes in a CBCS improves the robustness of the measurement.

Fuel cells with doped lanthanum gallate electrolyte

Science.gov (United States)

Feng, Man; Goodenough, John B.; Huang, Keqin; Milliken, Christopher

Single cells with doped lanthanum gallate electrolyte material were constructed and tested from 600 to 800°C. Both ceria and the electrolyte material were mixed with NiO powder respectively to form composite anodes. Doped lanthanum cobaltite was used exclusively as the cathode material. While high power density from the solid oxide fuel cells at 800°C was achieved. our results clearly indicate that anode overpotential is the dominant factor in the power loss of the cells. Better anode materials and anode processing methods need to be found to fully utilize the high ionic conductivity of the doped lanthanum galiate and achieve higher power density at 800°C from solid oxide fuel cells.

Downregulation of hPMC2 imparts chemotherapeutic sensitivity to alkylating agents in breast cancer cells.

Science.gov (United States)

Krishnamurthy, Nirmala; Liu, Lili; Xiong, Xiahui; Zhang, Junran; Montano, Monica M

2015-01-01

Triple negative breast cancer cell lines have been reported to be resistant to the cyotoxic effects of temozolomide (TMZ). We have shown previously that a novel protein, human homolog of Xenopus gene which Prevents Mitotic Catastrophe (hPMC2) has a role in the repair of estrogen-induced abasic sites. Our present study provides evidence that downregulation of hPMC2 in MDA-MB-231 and MDA-MB-468 breast cancer cells treated with temozolomide (TMZ) decreases cell survival. This increased sensitivity to TMZ is associated with an increase in number of apurinic/apyrimidinic (AP) sites in the DNA. We also show that treatment with another alkylating agent, BCNU, results in an increase in AP sites and decrease in cell survival. Quantification of western blot analyses and immunofluorescence experiments reveal that treatment of hPMC2 downregulated cells with TMZ results in an increase in γ-H2AX levels, suggesting an increase in double strand DNA breaks. The enhancement of DNA double strand breaks in TMZ treated cells upon downregulation of hPCM2 is also revealed by the comet assay. Overall, we provide evidence that downregulation of hPMC2 in breast cancer cells increases cytotoxicity of alkylating agents, representing a novel mechanism of treatment for breast cancer. Our data thus has important clinical implications in the management of breast cancer and brings forth potentially new therapeutic strategies.

Ovarian and Breast Cancer Spheres Are Similar in Transcriptomic Features and Sensitive to Fenretinide

Directory of Open Access Journals (Sweden)

Haiwei Wang

2013-01-01

Full Text Available Cancer stem cells (CSCs are resistant to chemotherapy and are ability to regenerate cancer cell populations, thus attracting much attention in cancer research. In this report, we first demonstrated that sphere cells from ovarian cancer cell line A2780 shared many features of CSCs, such as resistance to cisplatin and able to initiate tumors in an efficient manner. Then, we conducted cDNA microarray analysis on spheres from ovarian A2780 cells, and from breast MCF7 and SUM159 cells, and found that molecular pathways underlying spheres from these cancer cell lines were similar to a large extent, suggesting that similar mechanisms are involved in the genesis of CSCs in both ovarian and breast cancer types. In addition, we showed that spheres from these cancer types were highly sensitive to fenretinide, a stimulus of oxidative stress-mediated apoptosis in cancer cells. Thus, our results not only provide important insights into mechanisms underlying CSCs in ovarian and breast cancer, but also lead to the development of more sophisticated protocols of cancer therapy in near future.

Determination of catechins and catechin gallates in tissues by liquid chromatography with coulometric array detection and selective solid phase extraction.

Science.gov (United States)

Chu, Kai On; Wang, Chi Chiu; Chu, Ching Yan; Rogers, Michael Scott; Choy, Kwong Wai; Pang, Chi Pui

2004-10-25

Catechins levels in organ tissues, particularly liver, determined by published methods are unexpectedly low, probably due to the release of oxidative enzymes, metal ions and reactive metabolites from tissue cells during homogenization and to the pro-oxidant effects of ascorbic acid during sample processing in the presence of metal ions. We describe a new method for simultaneous analysis of eight catechins in tissue: (+)-catechin (C), (-)-epicatechin (EC), (-)-gallocatechin (GC), (-)-epigallocatechin (EGC), (-)-catechin gallate (CG), (-)-epicatechin gallate (ECG), (-)-gallocatechin gallate (GCG) and (-)-epigallocatechin gallate (EGCG) (Fig. 1). The new extraction procedure utilized a methanol/ethylacetate/dithionite (2:1:3) mixture during homogenization for simultaneous enzyme precipitation and antioxidant protection. Selective solid phase extraction was used to remove most interfering bio-matrices. Reversed phase HPLC with CoulArray detection was used to determine the eight catechins simultaneously within 25 min. Good linearity (>0.9922) was obtained in the range 20-4000 ng/g. The coefficients of variance (CV) were less than 5%. Absolute recovery ranged from 62 to 96%, accuracy 92.5 +/- 4.5 to 104.9 +/- 6%. The detection limit was 5 ng/g. This method is capable for determining catechins in rat tissues of liver, brain, spleen, and kidney. The method is robust, reproducible, with high recovery, and has been validated for both in vitro and in vivo sample analysis.

Age-specific interval breast cancers in Japan. Estimation of the proper sensitivity of screening using a population-based cancer registry

International Nuclear Information System (INIS)

Suzuki, Akihiko; Kuriyama, Shinichi; Kawai, Masaaki

2008-01-01

The age-specific sensitivity of a screening program was investigated using a population-based cancer registry as a source of false-negative cancer cases. A population-based screening program for breast cancer was run using either clinical breast examinations (CBE) alone or mammography combined with CBE in the Miyagi Prefecture from 1997 to 2002. Interval cancers were newly identified by linking the screening records to the population-based cancer registry to estimate the number of false-negative cases of screening program. Among 112071 women screened by mammography combined with CBE, the number of detected cancers, false-negative cases and the sensitivity were 289, 22 and 92.9%, respectively, based on the reports from participating municipalities. The number of newly found false-negative cases and corrected sensitivity when using the registry were 34 and 83.8%, respectively. In detected cancers, the sensitivity of screening by mammography combined with CBE in women ranging from 40 to 49 years of age based on a population-based cancer registry was much lower than that in women 50-59 and 60-69 years of age (40-49: 18, 71.4%, 50-59: 19, 85.8%, 60-69: 19, 87.2%). These data suggest that the accurate outcome of an evaluation of breast cancer screening must include the use of a population-based cancer registry for detecting false-negative cases. Screening by mammography combined with CBE may therefore not be sufficiently sensitive for women ranging from 40 to 49 years of age. (author)

Can-CSC-GBE: Developing Cost-sensitive Classifier with Gentleboost Ensemble for breast cancer classification using protein amino acids and imbalanced data.

Science.gov (United States)

Ali, Safdar; Majid, Abdul; Javed, Syed Gibran; Sattar, Mohsin

2016-06-01

Early prediction of breast cancer is important for effective treatment and survival. We developed an effective Cost-Sensitive Classifier with GentleBoost Ensemble (Can-CSC-GBE) for the classification of breast cancer using protein amino acid features. In this work, first, discriminant information of the protein sequences related to breast tissue is extracted. Then, the physicochemical properties hydrophobicity and hydrophilicity of amino acids are employed to generate molecule descriptors in different feature spaces. For comparison, we obtained results by combining Cost-Sensitive learning with conventional ensemble of AdaBoostM1 and Bagging. The proposed Can-CSC-GBE system has effectively reduced the misclassification costs and thereby improved the overall classification performance. Our novel approach has highlighted promising results as compared to the state-of-the-art ensemble approaches. Copyright © 2016 Elsevier Ltd. All rights reserved.

A comprehensive sensitivity analysis of microarray breast cancer classification under feature variability

Directory of Open Access Journals (Sweden)

Reinders Marcel JT

2009-11-01

Full Text Available Abstract Background Large discrepancies in signature composition and outcome concordance have been observed between different microarray breast cancer expression profiling studies. This is often ascribed to differences in array platform as well as biological variability. We conjecture that other reasons for the observed discrepancies are the measurement error associated with each feature and the choice of preprocessing method. Microarray data are known to be subject to technical variation and the confidence intervals around individual point estimates of expression levels can be wide. Furthermore, the estimated expression values also vary depending on the selected preprocessing scheme. In microarray breast cancer classification studies, however, these two forms of feature variability are almost always ignored and hence their exact role is unclear. Results We have performed a comprehensive sensitivity analysis of microarray breast cancer classification under the two types of feature variability mentioned above. We used data from six state of the art preprocessing methods, using a compendium consisting of eight diferent datasets, involving 1131 hybridizations, containing data from both one and two-color array technology. For a wide range of classifiers, we performed a joint study on performance, concordance and stability. In the stability analysis we explicitly tested classifiers for their noise tolerance by using perturbed expression profiles that are based on uncertainty information directly related to the preprocessing methods. Our results indicate that signature composition is strongly influenced by feature variability, even if the array platform and the stratification of patient samples are identical. In addition, we show that there is often a high level of discordance between individual class assignments for signatures constructed on data coming from different preprocessing schemes, even if the actual signature composition is identical

Local structure of gallate proton conductors

Energy Technology Data Exchange (ETDEWEB)

Giannici, F; Messana, D; Martorana, A [Universita degli Studi di Palermo, Dipartimento di Chimica Inorganica ed Analitica, Viale delle Scienze, I-90128 Palermo (Italy); Longo, A [CNR, Istituto per lo studio dei materiali nanostrutturati, Via Ugo La Malfa 153, I-90146 Palermo (Italy); Sciortino, L, E-mail: sciortino@pa.ismn.cnr.i

2009-11-15

Lanthanum barium gallate proton conductors are based on disconnected GaO{sub 4} groups. The insertion of hydroxyls in the LaBaGaO{sub 4} network proceeds through self-doping with Ba{sup 2+}, consequent O{sup 2-} vacancy formation to fulfill charge neutrality. With a structural investigation on self-doped LaBaGaO{sub 4} oxides using synchrotron XRD and EXAFS on the Ga K-edge, we find that: (a) the GaO{sub 4} tetrahedra retain their size throughout the whole series; (b) the GaO{sub 4} tetrahedra rotate as rigid bodies on hydration, leading to the formation of a network of shorter O-O configurations that are stabilized by hydrogen bonds; (c) contraction of the lattice occurs along the a unit cell axis, as a consequence of an overall structural rearrangement of the hydrated solid.

THE CLINICAL SIGNIFICANCE OF 99mTc-MIBI BREAST IMAGING IN THE DIAGNOSIS OF EARLY BREAST CANCER

Institute of Scientific and Technical Information of China (English)

任长才; 金少津; 邹强; 朱汇庆; 王红鹰; 梁春立

2001-01-01

Objective: To find an effective, sensitive, specific and noninvasive diagnostic method of breast cancer. Methods: 109 masses of 102 patients with breast lesions smaller than 2 cm in diameter were divided into three groups to undergo 99mTc-MIBI imaging and compared with the results of pathology examination. 20 cases without breast lesions were selected as control. Abnormal condensation of 99mTc-MIBI in the breast reaching 10% higher than that in the counterpart of the healthy breast was regarded as positive. Results: Of 32 breast cancers, positive imaging appeared in 25. Negative imaging were found in 31 of 38 benign breast lesions. Of 39 occult breast lesions, positive imaging appeared in 6 and 3 of them were breast cancer, 2 of 3 patients with slightly increased 99mTc-MIBI imaging threshold were breast cancer also. No positive imaging was found in the control group. The diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value of 99mTc-MIBI was 88.4%, 89.2%, 88.0%, 75.0% and 95.3%, respectively. Conclusion: 99mTc-MIBI imaging had higher sensitivity and accuracy in the diagnosis of breast cancer and differentiation between benign and malignant breast lesions. It could provide useful information for the diagnosis of clinically suspected breast cancer.

Characterization of Breast Lesions: Comparison of Digital Breast Tomosynthesis and Ultrasonography

International Nuclear Information System (INIS)

Kim, Sun Ah; Chang, Jung Min; Cho, Nariya; Yi, Ann; Moon, Woo Kyung

2015-01-01

To compare the diagnostic performance of digital breast tomosynthesis (DBT) and conventional breast ultrasound (US) to characterize breast lesions as benign or malignant. A total of 332 women, presenting for screening examinations or for breast biopsy between March and June 2012 were recruited to undergo digital mammography (DM), DBT, and breast US examination. Among them, 113 patients with 119 breast lesions depicted on DM were finally included. Three blinded radiologists performed an enriched reader study and reviewed the DBT and US images. Each reader analyzed the lesions in random order, assigned Breast Imaging Reporting and Data System (BI-RADS) descriptors, rated the images for the likelihood of malignancy (%) and made a BI-RADS final assessment. Diagnostic accuracy, as assessed by the area under the receiver operating characteristic curve, sensitivity, and specificity of DBT and US were compared. Among the 119 breast lesions depicted on DM, 75 were malignant and the remaining 44 were benign. The average diagnostic performance for characterizing breast lesions as benign or malignant in terms of area under the curve was 0.899 for DBT and 0.914 for US (p = 0.394). Mean sensitivity (97.3% vs. 98.7%, p = 0.508) and specificity (44.7% vs. 39.4%, p = 0.360) were also not significantly different. Digital breast tomosynthesis may provide similar reader lesion characterization performance to that of US for breast lesions depicted on DM

Characterization of Breast Lesions: Comparison of Digital Breast Tomosynthesis and Ultrasonography

Energy Technology Data Exchange (ETDEWEB)

Kim, Sun Ah [Department of Radiology, Human Medical Imaging & Intervention Center, Seoul 135-120 (Korea, Republic of); Chang, Jung Min; Cho, Nariya [Department of Radiology, Seoul National University Hospital, Seoul 110-744 (Korea, Republic of); Yi, Ann [Department of Radiology, Seoul National University Hospital Healthcare System Gangnam Center, Seoul 135-984 (Korea, Republic of); Moon, Woo Kyung [Department of Radiology, Seoul National University Hospital, Seoul 110-744 (Korea, Republic of)

2015-11-01

To compare the diagnostic performance of digital breast tomosynthesis (DBT) and conventional breast ultrasound (US) to characterize breast lesions as benign or malignant. A total of 332 women, presenting for screening examinations or for breast biopsy between March and June 2012 were recruited to undergo digital mammography (DM), DBT, and breast US examination. Among them, 113 patients with 119 breast lesions depicted on DM were finally included. Three blinded radiologists performed an enriched reader study and reviewed the DBT and US images. Each reader analyzed the lesions in random order, assigned Breast Imaging Reporting and Data System (BI-RADS) descriptors, rated the images for the likelihood of malignancy (%) and made a BI-RADS final assessment. Diagnostic accuracy, as assessed by the area under the receiver operating characteristic curve, sensitivity, and specificity of DBT and US were compared. Among the 119 breast lesions depicted on DM, 75 were malignant and the remaining 44 were benign. The average diagnostic performance for characterizing breast lesions as benign or malignant in terms of area under the curve was 0.899 for DBT and 0.914 for US (p = 0.394). Mean sensitivity (97.3% vs. 98.7%, p = 0.508) and specificity (44.7% vs. 39.4%, p = 0.360) were also not significantly different. Digital breast tomosynthesis may provide similar reader lesion characterization performance to that of US for breast lesions depicted on DM.

Cellular Morphology-Mediated Proliferation and Drug Sensitivity of Breast Cancer Cells

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Ryota Domura

2017-06-01

Full Text Available The interpretation of the local microenvironment of the extracellular matrix for malignant tumor cells is in intimate relation with metastatic spread of cancer cells involving the associated issues of cellular proliferation and drug responsiveness. This study was aimed to assess the combination of both surface topographies (fiber alignments and different stiffness of the polymeric substrates (poly(l-lactic acid and poly(ε-caprolactone, PLLA and PCL, respectively as well as collagen substrates (coat and gel to elucidate the effect of the cellular morphology on cellular proliferation and drug sensitivities of two different types of breast cancer cells (MDA-MB-231 and MCF-7. The morphological spreading parameter (nucleus/cytoplasm area ratio induced by the anthropogenic substrates has correlated intimately with the cellular proliferation and the drug sensitivity the half maximal inhibitory concentration (IC50 of cancer cells. This study demonstrated the promising results of the parameter for the evaluation of cancer cell malignancy.

Cellular Morphology-Mediated Proliferation and Drug Sensitivity of Breast Cancer Cells.

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Domura, Ryota; Sasaki, Rie; Ishikawa, Yuma; Okamoto, Masami

2017-06-06

The interpretation of the local microenvironment of the extracellular matrix for malignant tumor cells is in intimate relation with metastatic spread of cancer cells involving the associated issues of cellular proliferation and drug responsiveness. This study was aimed to assess the combination of both surface topographies (fiber alignments) and different stiffness of the polymeric substrates (poly(l-lactic acid) and poly(ε-caprolactone), PLLA and PCL, respectively) as well as collagen substrates (coat and gel) to elucidate the effect of the cellular morphology on cellular proliferation and drug sensitivities of two different types of breast cancer cells (MDA-MB-231 and MCF-7). The morphological spreading parameter (nucleus/cytoplasm area ratio) induced by the anthropogenic substrates has correlated intimately with the cellular proliferation and the drug sensitivity the half maximal inhibitory concentration (IC 50 ) of cancer cells. This study demonstrated the promising results of the parameter for the evaluation of cancer cell malignancy.

Breast density does not impact the ability of Videssa® Breast to detect breast cancer in women under age 50.

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David E Reese

Full Text Available Breast density is associated with reduced imaging resolution in the detection of breast cancer. A biochemical approach that is not affected by density would provide an important tool to healthcare professionals who are managing women with dense breasts and suspicious imaging findings. Videssa® Breast is a combinatorial proteomic biomarker assay (CPBA, comprised of Serum Protein Biomarkers (SPB and Tumor Associated Autoantibodies (TAAb integrated with patient-specific clinical data to produce a diagnostic score that reliably detects breast cancer (BC as an adjunctive tool to imaging. The performance of Videssa® Breast was evaluated in the dense (a and b and non-dense (c and d groups in a population of n = 545 women under age 50. The sensitivity and specificity in the dense breast group were calculated to be 88.9% and 81.2%, respectively, and 92.3% and 86.6%, respectively, for the non-dense group. No significant differences were observed in the sensitivity (p = 1.0 or specificity (p = 0.18 between these groups. The NPV was 99.3% and 99.1% in non-dense and dense groups, respectively. Unlike imaging, Videssa® Breast does not appear to be impacted by breast density; it can effectively detect breast cancer in women with dense and non-dense breasts alike. Thus, Videssa® Breast provides a powerful tool for healthcare providers when women with dense breasts present with challenging imaging findings. In addition, Videssa® Breast provides assurance to women with dense breasts that they do not have breast cancer, reducing further anxiety in this higher risk patient population.

Diagnostic value of dynamic and morphologic breast MRI analysis in the diagnosis of breast cancer

International Nuclear Information System (INIS)

Stusińska, Małgorzata; Szabo-Moskal, Jadwiga; Bobek-Billewicz, Barbara

2014-01-01

Mammography is the most widely used method of breast imaging. However, its low sensitivity poses a problem. Breast MRI is one of so the called “complementary” breast imaging methods. The purpose of this study was to improve the specificity of breast MRI by combining 2 methods: dynamic and morphologic analysis of enhancing lesions. 222 women aged 19–76 years, who underwent breast MRI examination between November 2002 and April 2004 at the Radiology Department of Oncology Center in Bydgoszcz, were included in this study. The pathological examination revealed cancer in 55 women (25%). No cancer was found in 167 women (75%), 56 of which were verified pathologically, 111 by cytology and/or during follow-up (at least 24 months). Results of breast MRI were positive in 80 women (36%), in 54 of which cancer was found during pathological examination, 26 breast MRI results were false positive. Sensitivity and specificity of breast MRI for dynamic analysis were 87% and 72%, respectively; in case of morphologic analysis 98% and 74%, respectively. The combined dynamic and morphologic analysis achieved high (84%) specificity without loss of sensitivity (98%). The difference in specificity between the evaluated methods was statistically significant (p<0.05). The combined dynamic and morphologic breast MRI analysis is a useful method for the diagnosis of breast cancer

Pharmacokinetic study of gallocatechin-7-gallate from Pithecellobium clypearia Benth. in rats

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Chao Li

2016-01-01

Full Text Available The pharmacokinetic profile of gallocatechin-7-gallate (J10688 was studied in rats after intravenous administration. Male and female Sprague-Dawley (SD rats received 1, 3, and 10 mg/kg (i.v. of J10688 and plasma drug concentrations were determined by a high performance liquid chromatography-mass spectrometry (LC–MS method. The pharmacokinetic software Data Analysis System (Version 3.0 was used to calculate the pharmacokinetic parameters. For different i.v. doses of J10688, the mean peak plasma concentration (C0 values ranged from 11.26 to 50.82 mg/L, and mean area under the concentration-time curve (AUC0–t values ranged from 1.75 to 11.80 (mg·h/L. J10688 lacked dose-dependent pharmacokinetic properties within doses between 1 and 10 mg/kg, based on the power model. The method developed in this study was sensitive, precise, and stable. The pharmacokinetic properties of J10688 in SD rats were shown to have rapid distribution and clearance values. These pharmacokinetic results may contribute to an improved understanding of the pharmacological actions of J10688.

Partial-Breast Irradiation Versus Whole-Breast Irradiation for Early-Stage Breast Cancer: A Cost-Effectiveness Analysis

International Nuclear Information System (INIS)

Sher, David J.; Wittenberg, Eve; Suh, W. Warren; Taghian, Alphonse G.; Punglia, Rinaa S.

2009-01-01

Purpose: Accelerated partial-breast irradiation (PBI) is a new treatment paradigm for patients with early-stage breast cancer. Although PBI may lead to greater local recurrence rates, it may be cost-effective because of better tolerability and lower cost. We aim to determine the incremental cost-effectiveness of PBI compared with whole-breast radiation therapy (WBRT) for estrogen receptor-positive postmenopausal women treated for early-stage breast cancer. Methods and Materials: We developed a Markov model to describe health states in the 15 years after radiotherapy for early-stage breast cancer. External beam (EB) and MammoSite (MS) PBI were considered and assumed to be equally effective, but carried different costs. Patients received tamoxifen, but not chemotherapy. Utilities, recurrence risks, and costs were adapted from the literature; the baseline utility for no disease after radiotherapy was set at 0.92. Probabilistic sensitivity analyses were performed to model uncertainty in the PBI hazard ratio, recurrence pattern, and patient utilities. Costs (in 2004 US dollars) and quality-adjusted life-years were discounted at 3%/y. Results: The incremental cost-effectiveness ratio for WBRT compared with EB-PBI was $630,000/quality-adjusted life-year; WBRT strongly dominated MS-PBI. One-way sensitivity analysis found that results were sensitive to PBI hazard ratio, recurrence pattern, baseline recurrence risk, and no evidence of disease PBI utility values. Probabilistic sensitivity showed that EB-PBI was the most cost-effective technique over a wide range of assumptions and societal willingness-to-pay values. Conclusions: EB-PBI was the most cost-effective strategy for postmenopausal women with early-stage breast cancer. Unless the quality of life after MS-PBI proves to be superior, it is unlikely to be cost-effective.

A Presurgical Study of Lecithin Formulation of Green Tea Extract in Women with Early Breast Cancer.

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Lazzeroni, Matteo; Guerrieri-Gonzaga, Aliana; Gandini, Sara; Johansson, Harriet; Serrano, Davide; Cazzaniga, Massimiliano; Aristarco, Valentina; Macis, Debora; Mora, Serena; Caldarella, Pietro; Pagani, Gianmatteo; Pruneri, Giancarlo; Riva, Antonella; Petrangolini, Giovanna; Morazzoni, Paolo; DeCensi, Andrea; Bonanni, Bernardo

2017-06-01

Epidemiologic data support an inverse association between green tea intake and breast cancer risk. Greenselect Phytosome (GSP) is a lecithin formulation of a caffeine-free green tea catechin extract. The purpose of the study was to determine the tissue distribution of epigallocatechin-3-O-gallate (EGCG) and its effect on cell proliferation and circulating biomarkers in breast cancer patients. Twelve early breast cancer patients received GSP 300 mg, equivalent to 44.9 mg of EGCG, daily for 4 weeks prior to surgery. The EGCG levels were measured before (free) and after (total) enzymatic hydrolysis by HPLC-MS/MS in plasma, urine, breast cancer tissue, and surrounding normal breast tissue. Fasting blood samples were taken at baseline, before the last administration, and 2 hours later. Repeated administration of GSP achieved levels of total EGCG ranging from 17 to 121 ng/mL in plasma. Despite a high between-subject variability, total EGCG was detectable in all tumor tissue samples collected up to 8 ng/g. Median total EGCG concentration was higher in the tumor as compared with the adjacent normal tissue (3.18 ng/g vs. 0 ng/g, P = 0.02). Free EGCG concentrations ranged from 8 to 65.8 ng/mL in plasma ( P between last administration and 2 hours after breast tumor tissue and is associated with antiproliferative effects on breast cancer tissue. Cancer Prev Res; 10(6); 363-9. ©2017 AACR . ©2017 American Association for Cancer Research.

Radio-sensitization by Piper longumine of human breast adenoma MDA-MB-231 cells in vitro.

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Yao, Jian-Xin; Yao, Zhi-Feng; Li, Zhan-Feng; Liu, Yong-Biao

2014-01-01

The current study investigated the effects of Piper longumine on radio-sensitization of human breast cancer MDA-MB-231 cells and underlying mechanisms. Human breast cancer MDA-MB-231 cells were cultured in vitro and those in logarithmic growth phase were selected for experiments divided into four groups: control, X-ray exposed, Piper longumine, and Piper longumine combined with X-rays. Conogenic assays were performed to determine the radio-sensitizing effects. Cell survival curves were fitted by single-hit multi-target model and then the survival fraction (SF), average lethal dose (D0), quasi-threshold dose (Dq) and sensitive enhancement ratio (SER) were calculated. Cell apoptosis was analyzed by flow cytometry (FCM).Western blot assays were employed for expression of apoptosis-related proteins (Bc1-2 and Bax) after treatment with Piper longumine and/or X-ray radiation. The intracellular reactive oxygen species (ROS) level was detected by FCM with a DCFH-DA probe. The cloning formation capacity was decreased in the group of piperlongumine plus radiation, which displayed the values of SF2, D0, Dq significantly lower than those of radiation alone group and the sensitive enhancement ratio (SER) of D0 was1.22 and 1.29, respectively. The cell apoptosis rate was increased by the combination treatment of Piper longumine and radiation. Piper longumine increased the radiation-induced intracellular levels of ROS. Compared with the control group and individual group, the combination group demonstrated significantly decreased expression of Bcl-2 with increased Bax. Piper longumine at a non-cytotoxic concentration can enhance the radio-sensitivity of MDA- MB-231cells, which may be related to its regulation of apoptosis-related protein expression and the increase of intracellular ROS level, thus increasing radiation-induced apoptosis.

Reactivation of estrogen receptor α by vorinostat sensitizes mesenchymal-like triple-negative breast cancer to aminoflavone, a ligand of the aryl hydrocarbon receptor.

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Stark, Karri; Burger, Angelika; Wu, Jianmei; Shelton, Phillip; Polin, Lisa; Li, Jing

2013-01-01

Aminoflavone (AF) acts as a ligand of the aryl hydrocarbon receptor (AhR). Expression of estrogen receptor α (ERα) and AhR-mediated transcriptional induction of CYP1A1 can sensitize breast cancer cells to AF. The objective of this study was to investigate the combined antitumor effect of AF and the histone deacetylase inhibitor vorinostat for treating mesenchymal-like triple-negative breast cancer (TNBC) as well as the underlying mechanisms of such treatment. In vitro antiproliferative activity of AFP464 (AF prodrug) in breast cancer cell lines was evaluated by MTS assay. In vitro, the combined effect of AFP464 and vorinostat on cell proliferation was assessed by the Chou-Talalay method. In vivo, antitumor activity of AFP464, given alone and in combination with vorinostat, was studied using TNBC xenograft models. Knockdown of ERα was performed using specific, small-interfering RNA. Western blot, quantitative RT-PCR, immunofluorescence, and immunohistochemical staining were performed to study the mechanisms underlying the combined antitumor effect. Luminal and basal A subtype breast cancer cell lines were sensitive to AFP464, whereas basal B subtype or mesenchymal-like TNBC cells were resistant. Vorinostat sensitized mesenchymal-like TNBC MDA-MB-231 and Hs578T cells to AFP464. It also potentiated the antitumor activity of AFP464 in a xenograft model using MDA-MB-231 cells. In vitro and in vivo mechanistic studies suggested that vorinostat reactivated ERα expression and restored AhR-mediated transcriptional induction of CYP1A1. The response of breast cancer cells to AF or AFP464 was associated with their gene expression profile. Vorinostat sensitized mesenchymal-like TNBC to AF, at least in part, by reactivating ERα expression and restoring the responsiveness of AhR to AF.

New treatment option for women with hormone-sensitive breast cancer

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A drug used for treating breast cancer, known as exemestane, is more effective than a common breast cancer prevention drug, tamoxifen, in preventing breast cancer recurrence in young women who also receive post-surgical treatment to suppress ovarian funct

New Treatment Option for Young Women with Hormone-Sensitive Breast Cancer

Science.gov (United States)

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... breast cancer, defined as estrogen and/or progesterone receptor-positive breast cancer, represents 79 percent of breast ...

Breast cancer screening effect across breast density strata: A case-control study.

Science.gov (United States)

van der Waal, Daniëlle; Ripping, Theodora M; Verbeek, André L M; Broeders, Mireille J M

2017-01-01

Breast cancer screening is known to reduce breast cancer mortality. A high breast density may affect this reduction. We assessed the effect of screening on breast cancer mortality in women with dense and fatty breasts separately. Analyses were performed within the Nijmegen (Dutch) screening programme (1975-2008), which invites women (aged 50-74 years) biennially. Performance measures were determined. Furthermore, a case-control study was performed for women having dense and women having fatty breasts. Breast density was assessed visually with a dichotomized Wolfe scale. Breast density data were available for cases. The prevalence of dense breasts among controls was estimated with age-specific rates from the general population. Sensitivity analyses were performed on these estimates. Screening performance was better in the fatty than in the dense group (sensitivity 75.7% vs 57.8%). The mortality reduction appeared to be smaller for women with dense breasts, with an odds ratio (OR) of 0.87 (95% CI 0.52-1.45) in the dense and 0.59 (95% CI 0.44-0.79) in the fatty group. We can conclude that high density results in lower screening performance and appears to be associated with a smaller mortality reduction. Breast density is thus a likely candidate for risk-stratified screening. More research is needed on the association between density and screening harms. © 2016 UICC.

Targeting cyclin B1 inhibits proliferation and sensitizes breast cancer cells to taxol

International Nuclear Information System (INIS)

Androic, Ilija; Krämer, Andrea; Yan, Ruilan; Rödel, Franz; Gätje, Regine; Kaufmann, Manfred; Strebhardt, Klaus; Yuan, Juping

2008-01-01

Cyclin B1, the regulatory subunit of cyclin-dependent kinase 1 (Cdk1), is essential for the transition from G2 phase to mitosis. Cyclin B1 is very often found to be overexpressed in primary breast and cervical cancer cells as well as in cancer cell lines. Its expression is correlated with the malignancy of gynecological cancers. In order to explore cyclin B1 as a potential target for gynecological cancer therapy, we studied the effect of small interfering RNA (siRNA) on different gynecological cancer cell lines by monitoring their proliferation rate, cell cycle profile, protein expression and activity, apoptosis induction and colony formation. Tumor formation in vivo was examined using mouse xenograft models. Downregulation of cyclin B1 inhibited proliferation of several breast and cervical cancer cell lines including MCF-7, BT-474, SK-BR-3, MDA-MB-231 and HeLa. After combining cyclin B1 siRNA with taxol, we observed an increased apoptotic rate accompanied by an enhanced antiproliferative effect in breast cancer cells. Furthermore, control HeLa cells were progressively growing, whereas the tumor growth of HeLa cells pre-treated with cyclin B1 siRNA was strongly inhibited in nude mice, indicating that cyclin B1 is indispensable for tumor growth in vivo. Our data support the notion of cyclin B1 being essential for survival and proliferation of gynecological cancer cells. Concordantly, knockdown of cyclin B1 inhibits proliferation in vitro as well as in vivo. Moreover, targeting cyclin B1 sensitizes breast cancer cells to taxol, suggesting that specific cyclin B1 targeting is an attractive strategy for the combination with conventionally used agents in gynecological cancer therapy

Paramagnetic centers in two phases of manganese-doped lanthanum gallate

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Vazhenin, V. A.; Potapov, A. P.; Guseva, V. B.; Artyomov, M. Yu.

2009-05-01

An EPR study of two phases of manganese-doped lanthanum gallate (with a first-order structural transition occurring at 430 K) has revealed Gd3+, Fe3+, and Mn4+ centers at room temperature and 438 K. The parameters of spin Hamiltonians are determined for the Gd3+, Fe3+, and Mn4+ rhombohedral centers in the high-temperature phase (with no other centers found here) and for the monoclinic center Gd3+ in the low-temperature phase. Both in the orthorhombic and in the rhombohedral phase, crystallographic twins (or ferroelastic domains) are observed.

Lanthanum gallate substrates for epitaxial high-temperature superconducting thin films

Science.gov (United States)

Sandstrom, R. L.; Giess, E. A.; Gallagher, W. J.; Segmuller, A.; Cooper, E. I.

1988-11-01

It is demonstrated that lanthanum gallate (LaGaO3) has considerable potential as an electronic substrate material for high-temperature superconducting films. It provides a good lattice and thermal expansion match to YBa2Cu3O(7-x), can be grown in large crystal sizes, is compatible with high-temperature film processing, and has a reasonably low dielectric constant and low dielectric losses. Epitaxial YBa2Cu3O(7-x) films grown on LaGaO3 single-crystal substrates by three techniques have zero resistance between 87 and 91 K.

Sensitivity of docetaxel-resistant MCF-7 breast cancer cells to microtubule-destabilizing agents including vinca alkaloids and colchicine-site binding agents.

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Richard C Wang

Full Text Available One of the main reasons for disease recurrence in the curative breast cancer treatment setting is the development of drug resistance. Microtubule targeted agents (MTAs are among the most commonly used drugs for the treatment of breaset cancer and therefore overcoming taxane resistance is of primary clinical importance. Our group has previously demonstrated that the microtubule dynamics of docetaxel-resistant MCF-7TXT cells are insensitivity to docetaxel due to the distinct expression profiles of β-tubulin isotypes in addition to the high expression of p-glycoprotein (ABCB1. In the present investigation we examined whether taxane-resistant breast cancer cells are more sensitive to microtubule destabilizing agents including vinca alkaloids and colchicine-site binding agents (CSBAs than the non-resistant cells.Two isogenic MCF-7 breast cancer cell lines were selected for resistance to docetaxel (MCF-7TXT and the wild type parental cell line (MCF-7CC to examine if taxane-resistant breast cancer cells are sensitive to microtubule-destabilizing agents including vinca alkaloids and CSBAs. Cytotoxicity assays, immunoblotting, indirect immunofluorescence and live imaging were used to study drug resistance, apoptosis, mitotic arrest, microtubule formation, and microtubule dynamics.MCF-7TXT cells were demonstrated to be cross resistant to vinca alkaloids, but were more sensitive to treatment with colchicine compared to parental non-resistant MCF-7CC cells. Cytotoxicity assays indicated that the IC50 of MCF-7TXT cell to vinorelbine and vinblastine was more than 6 and 3 times higher, respectively, than that of MCF-7CC cells. By contrast, the IC50 of MCF-7TXT cell for colchincine was 4 times lower than that of MCF-7CC cells. Indirect immunofluorescence showed that all MTAs induced the disorganization of microtubules and the chromatin morphology and interestingly each with a unique pattern. In terms of microtubule and chromain morphology, MCF-7TXT cells were

Sensitized chemiluminescence of 2-phenyl-4,5-di(2-furyl)-1H-imidazole/K₃Fe(CN)₆/propyl gallate system combining with solid-phase extraction for the determination of propyl gallate in edible oil.

Science.gov (United States)

Kang, Jing; Han, Lu; Chen, Zhonglin; Shen, Jimin; Nan, Jun; Zhang, Yihua

2014-09-15

In this paper, a novel chemiluminescence (CL) method has been developed for the determination of propyl gallate (PG). The proposed method was based on the enhancing effect of PG on the CL signal of 2-phenyl-4,5-di(2-furyl)-1H-imidazole (PDFI) and K3Fe(CN)6 reaction in an alkaline solution. Under the optimum conditions, the enhanced CL intensity was linearly related to the concentration of PG. The linear range of the calibration curve was 0.05-8 μg/mL, and the corresponding detection limit (3σ) was 0.036 μg/mL. The relative standard deviation for determining 1.0 μg/mL PG was 2.8% (n=11). The proposed method has been successfully applied to the determination of PG in edible oil. The edible oil samples were prepared by the solid-phase extraction (SPE) with a C18 column served as the stationary phase. Furthermore, the possible CL mechanism was also discussed briefly based on the photoluminescence (PL) and CL spectra. Copyright © 2014 Elsevier Ltd. All rights reserved.

Carboplatin treatment of antiestrogen-resistant breast cancer cells

DEFF Research Database (Denmark)

Larsen, Mathilde S; Yde, Christina Westmose; Christensen, Ib J

2012-01-01

Antiestrogen resistance is a major clinical problem in current breast cancer treatment. Therefore, biomarkers and new treatment options for antiestrogen-resistant breast cancer are needed. In this study, we investigated whether antiestrogen‑resistant breast cancer cell lines have increased...... sensitivity to carboplatin, as it was previously shown with cisplatin, and whether low Bcl-2 expression levels have a potential value as marker for increased carboplatin sensitivity. Breast cancer cells resistant to the pure antiestrogen fulvestrant, and two out of four cell lines resistant...... to the antiestrogen tamoxifen, were more sensitive to carboplatin treatment compared to the parental MCF-7 cell line. This indicates that carboplatin may be an advantageous treatment in antiestrogen‑resistant breast cancer; however, a marker for increased sensitivity would be needed. Low Bcl-2 expression...

The antipsychotic drug chlorpromazine enhances the cytotoxic effect of tamoxifen in tamoxifen-sensitive and tamoxifen-resistant human breast cancer cells

DEFF Research Database (Denmark)

Yde, Christina Westmose; Clausen, Mathias Porsmose; Bennetzen, Martin

2009-01-01

, the compound is now also recognized as a multitargeting drug with diverse potential applications, for example, it has antiproliferative properties and it can reverse resistance toward antibiotics in bacteria. Furthermore, chlorpromazine can reverse multidrug resistance caused by overexpression of P......Tamoxifen resistance is a major clinical problem in the treatment of estrogen receptor a-positive breast tumors. It is, at present, unclear what exactly causes tamoxifen resistance. For decades, chlorpromazine has been used for treating psychotic diseases, such as schizophrenia. However......-sensitive breast cancer cell line, MCF-7, and in a tamoxifen-resistant cell line, established from the MCF-7 cells. Tamoxifen-sensitive and tamoxifen-resistant cells were killed equally well by combined treatment with chlorpromazine and tamoxifen. This synergistic effect could be prevented by addition of estrogen...

Theranostic pH-sensitive nanoparticles for highly efficient targeted delivery of doxorubicin for breast tumor treatment.

Science.gov (United States)

Pan, Changqie; Liu, Yuqing; Zhou, Minyu; Wang, Wensheng; Shi, Min; Xing, Malcolm; Liao, Wangjun

2018-01-01

A multifunctional theranostic nanoplatform integrated with environmental responses has been developed rapidly over the past few years as a novel treatment strategy for several solid tumors. We synthesized pH-sensitive poly(β-thiopropionate) nanoparticles with a supermagnetic core and folic acid (FA) conjugation (FA-doxorubicin-iron oxide nanoparticles [FA-DOX@ IONPs]) to deliver an antineoplastic drug, DOX, for the treatment of folate receptor (FR)-overexpressed breast cancer. In addition to an imaging function, the nanoparticles can release their payloads in response to an environment of pH 5, such as the acidic environment found in tumors. After chemical ( 1 H nuclear magnetic resonance) and physical (morphology and super-magnetic) characterization, FA-DOX@IONPs were shown to demonstrate pH-dependent drug release profiles. Western blotting analysis revealed the expression of FRs in three breast cancer cell lines, MCF-7, BT549, and MD-MBA-231. The cell counting kit-8 assay and transmission electron microscopy showed that FA-DOX@IONPs had the strongest cytotoxicity against breast cancer cells, compared with free DOX and non-FR targeted nanoparticles (DOX@IONPs), and caused cellular apoptosis. The FA-DOX@IONP-mediated cellular uptake and intracellular internalization were clarified by fluorescence microscopy. FA-DOX@IONPs plus magnetic field treatment suppressed in vivo tumor growth in mice to a greater extent than either treatment alone; furthermore, the nanoparticles exerted no toxicity against healthy organs. Magnetic resonance imaging was successfully applied to monitor the nanoparticle accumulation. Our results suggest that theranostic pH-sensitive nanoparticles with dual targeting could enhance the available therapies for cancer.

Targeting cyclin B1 inhibits proliferation and sensitizes breast cancer cells to taxol

Directory of Open Access Journals (Sweden)

Strebhardt Klaus

2008-12-01

Full Text Available Abstract Background Cyclin B1, the regulatory subunit of cyclin-dependent kinase 1 (Cdk1, is essential for the transition from G2 phase to mitosis. Cyclin B1 is very often found to be overexpressed in primary breast and cervical cancer cells as well as in cancer cell lines. Its expression is correlated with the malignancy of gynecological cancers. Methods In order to explore cyclin B1 as a potential target for gynecological cancer therapy, we studied the effect of small interfering RNA (siRNA on different gynecological cancer cell lines by monitoring their proliferation rate, cell cycle profile, protein expression and activity, apoptosis induction and colony formation. Tumor formation in vivo was examined using mouse xenograft models. Results Downregulation of cyclin B1 inhibited proliferation of several breast and cervical cancer cell lines including MCF-7, BT-474, SK-BR-3, MDA-MB-231 and HeLa. After combining cyclin B1 siRNA with taxol, we observed an increased apoptotic rate accompanied by an enhanced antiproliferative effect in breast cancer cells. Furthermore, control HeLa cells were progressively growing, whereas the tumor growth of HeLa cells pre-treated with cyclin B1 siRNA was strongly inhibited in nude mice, indicating that cyclin B1 is indispensable for tumor growth in vivo. Conclusion Our data support the notion of cyclin B1 being essential for survival and proliferation of gynecological cancer cells. Concordantly, knockdown of cyclin B1 inhibits proliferation in vitro as well as in vivo. Moreover, targeting cyclin B1 sensitizes breast cancer cells to taxol, suggesting that specific cyclin B1 targeting is an attractive strategy for the combination with conventionally used agents in gynecological cancer therapy.

Concentration Study of High Sensitive C - reactive Protein and some Serum Trace Elements in Patients with Benign and Malignant Breast Tumor.

Science.gov (United States)

Abdollahi, Alireza; Ali-Bakhshi, Abbas; Farahani, Zahra

2015-10-01

Background : Breast cancer is the most common invasive cancer in females worldwide. It accounts for 16% of all female cancers and 22.9% of invasive cancers in women. 18.2% of all cancer deaths worldwide including both males and females are from breast cancer. In this study we compared few serum elements in patients with benign and malignant breast tumor to find any related prognostic and predictive value. A case-control study was carried out in a hospital (Tehran - Iran) in 2012. Target population was divided in 2 groups; subjects with benign and malignant breast tumors. We did preoperative hematological test. Five milliliter fasting blood vein was collected, centrifuged in 3000 g for 15 minutes to obtain serum. We measured serum Calcium (Ca), Phosphorus (P), Magnesium (Mg), Zinc (Zn), and high sensitive-CRP, analyzed statistically and compared recorded elements in 2 groups by software package SPSS version 16. The level of significant was considered P benign and malignant breast disease.

Atom states and interatomic interactions in complex perovskite-like oxides. Communication XX. Origin of electron-ionic conductivity in lanthanum gallates doped with strontium and chromium

International Nuclear Information System (INIS)

Chezhina, N.V.; Zolotukhina, N.V.; Pijr, I.V.

2006-01-01

Magnetic susceptibilities and electric conductivities of solid solutions based on lanthanum gallate containing chromium and strontium atoms in the ratio of 10 : 2 were studied. It was shown that no partial oxidation of chromium to Cr(IV) occurs when lanthanum gallate is doped with chromium and strontium simultaneously, whereas the ionic conductivity is associated with the appearance of vacancies stabilized by chromium atoms in the oxygen sublattice [ru

Highly Sensitive and High-Throughput Method for the Analysis of Bisphenol Analogues and Their Halogenated Derivatives in Breast Milk.

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Niu, Yumin; Wang, Bin; Zhao, Yunfeng; Zhang, Jing; Shao, Bing

2017-12-06

The structural analogs of bisphenol A (BPA) and their halogenated derivatives (together termed BPs) have been found in the environment, food, and even the human body. Limited research showed that some of them exhibited toxicities that were similar to or even greater than that of BPA. Therefore, adverse health effects for BPs were expected for humans with low-dose exposure in early life. Breast milk is an excellent matrix and could reflect fetuses' and babies' exposure to contaminants. Some of the emerging BPs may present with trace or ultratrace levels in humans. However, existing analytical methods for breast milk cannot quantify these BPs simultaneously with high sensitivity using a small sampling weight, which is important for human biomonitoring studies. In this paper, a method based on Bond Elut Enhanced Matrix Removal-Lipid purification, pyridine-3-sulfonyl chloride derivatization, and liquid chromatography electrospray tandem mass spectrometry was developed. The method requires only a small quantity of sample (200 μL) and allowed for the simultaneous determination of 24 BPs in breast milk with ultrahigh sensitivity. The limits of quantitation of the proposed method were 0.001-0.200 μg L -1 , which were 1-6.7 times lower than the only study for the simultaneous analysis of bisphenol analogs in breast milk based on a 3 g sample weight. The mean recoveries ranged from 86.11% to 119.05% with relative standard deviation (RSD) ≤ 19.5% (n = 6). Matrix effects were within 20% with RSD bisphenol F (BPF), bisphenol S (BPS), and bisphenol AF (BPAF) were detected. BPA was still the dominant BP, followed by BPF. This is the first report describing the occurrence of BPF and BPAF in breast milk.

Understanding drugs in breast cancer through drug sensitivity screening

NARCIS (Netherlands)

K. Uhr (Katharina); W.J.C. Prager-van der Smissen (Wendy); A.A.J. Heine (Anouk); B. Ozturk (Bahar); M. Smid (Marcel); H.W.H. Göhlmann (Hinrich W. H.); A. Jager (Agnes); J.A. Foekens (John); J.W.M. Martens (John)

2015-01-01

textabstractWith substantial numbers of breast tumors showing or acquiring treatment resistance, it is of utmost importance to develop new agents for the treatment of the disease, to know their effectiveness against breast cancer and to understand their relationships with other drugs to best assign

Lanthanum gallate substrates for epitaxial high-temperature superconducting thin films

International Nuclear Information System (INIS)

Sandstrom, R.L.; Giess, E.A.; Gallagher, W.J.; Segmueller, A.; Cooper, E.I.; Chisholm, M.F.; Gupta, A.; Shinde, S.; Laibowitz, R.B.

1988-01-01

We demonstrate that lanthanum gallate (LaGaO 3 ) has considerable potential as an electronic substrate material for high-temperature superconducting films. It provides a good lattice and thermal expansion match to YBa 2 Cu 3 O/sub 7-//sub x/, can be grown in large crystal sizes, is compatible with high-temperature film processing, and has a reasonably low dielectric constant (ε≅25) and low dielectric losses. Epitaxial YBa 2 Cu 3 O/sub 7-//sub x/ films grown on LaGaO 3 single-crystal substrates by three techniques have zero resistance between 87 and 91 K

Evaluation of non-genomic, clinical risk and survival results in endocrine-sensitive, HER-2 negative, node negative breast cancer.

Science.gov (United States)

Baena Cañada, José M; Gámez Casado, Salvador; Rodríguez Pérez, Lourdes; Quílez Cutillas, Alicia; Cortés Carmona, Cristina; Rosado Varela, Petra; Estalella Mendoza, Sara; Ramírez Daffós, Patricia; Benítez Rodríguez, Encarnación

2018-02-28

In endocrine-sensitive, HER-2 negative, node negative breast cancer, the presence of a low genomic risk allows treatment with adjuvant endocrine therapy alone, obtaining excellent survival rates. The justification for this study is to show that excellent survival rates are also obtained by treating with adjuvant hormone therapy alone, based on clinical risk assessment. A descriptive, observational and retrospective study was performed between 2006 and 2016 with endocrine-sensitive, HER-2 negative, node negative breast cancer, greater than 1cm or between 0.6 and 1cm with unfavourable features. Retrospective review of health records. Mortality data of the National Registry of Deaths. A total of 203 patients were evaluable for survival. One hundred and twenty-three (60.50%) were treated with adjuvant endocrine therapy alone, 77 (37.90%) with chemotherapy and endocrine therapy, one (0.50%) with chemotherapy alone and 2 (1%) were not treated. The overall survival rate at 5 years was 97% (95% confidence interval [CI] 94-100). Distant recurrence-free interval was 94% (95% CI 90-98). In the subgroup of patients treated with endocrine therapy alone, overall survival and distant recurrence-free interval rates at 5 years were 98% (95% CI 95-100) and 97% (95% CI 93-100), respectively. Patients with endocrine-sensitive, HER-2-negative, node negative breast cancer treated with endocrine therapy alone according to their clinical risk have similar survival outcomes as those treated with endocrine therapy according to their genomic risk. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

The structure of new germanates, gallates, borates and silicates with laser, piezo, ferroelectric and ion conducting properties

International Nuclear Information System (INIS)

Belokonev, E.L.

1994-01-01

The results of structure investigation of more than 50 new crystalline germanates, gallates, borogermanates, borates, and silicates with laser, piezo, ferroelectric, and ion-conducting properties are described. The structure - properties relationship is examined. 71 refs.; 24 figs.; 10 tabs

Imprinted propyl gallate electrochemical sensor based on graphene/single walled carbon nanotubes/sol-gel film.

Science.gov (United States)

Xu, Guilin; Chi, Yu; Li, Lu; Liu, Shouhua; Kan, Xianwen

2015-06-15

A novel imprinted sol-gel electrochemical sensor for the determination of propyl gallate (PG) was developed based on a composite of graphene and single walled carbon nanotubes (GR-SWCNTs). It was fabricated by stepwise modifying GR-SWCNTs and molecularly imprinted polymers and stored in 0.10 mol L(-1) phosphate buffer solution pH 6.0, which endowed the sensor good sensitivity and selective recognition towards template molecules. The morphology and specific adsorption capacity of the sensor was characterized by scanning electron microscope and electrochemical methods, respectively. Under the optimized conditions, a linear range of the sensor to PG was 8.0 × 10(-8)-2.6 × 10(-3)mo lL(-1) with a limit of detection of 5.0 × 10(-8)mol L(-1) (S/N=3). The sensor exhibited specificity and selectivity towards template molecules as well as excellent reproducibility, regeneration and stability. Furthermore, the sensor could be applied to determine PG in edible oils, instant noodles and cookies with satisfactory results. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Monocarboxylate transporter 1 enhances the sensitivity of breast cancer cells to 3-bromopyruvate in vitro].

Science.gov (United States)

Li, Qi-Xiang; Zhang, Pei; Liu, Fang; Wang, Xian-Zhi; Li, Lu; Wang, Zhong-Kun; Jiang, Chen-Chen; Zheng, Hai-Lun; Liu, Hao

2017-05-20

To investigate the role of monocarboxylate transporter 1 (MCT1) in enhancing the sensitivity of breast cancer cells to 3-bromopyruvate (3-BrPA). The inhibitory effect of 3-BrPA on the proliferation of breast cancer cells was assessed with MTT assay, and brominated propidium bromide single staining flow cytometry was used for detecting the cell apoptosis. An ELISA kit was used to detect the intracellular levels of hexokinase II, lactate dehydrogenase, lactate, and adenosine triphosphate, and Western blotting was performed to detect the expression of MCT1. MDA-MB-231 cells were transiently transfected with MCT1 cDNA for over-expressing MCT1, and the effect of 3-BrPA on the cell proliferation and adenosine triphosphate level was deteced. 3-BrPA did not produce significant effects on the proliferation and apoptosis of MDA-MB-231 cells, and the cells treated with 200 µmol/L 3-BrPA for 24 h showed an inhibition rate and an apoptosis rate of only 8.72% and 7.8%, respectively. The same treatment, however, produced an inhibition rate and an apoptosis rate of 84.6% and 82.3% in MCF-7 cells, respectively. In MDA-MB-231 cells with MCT1 overexpression, 200 µmol/L 3-BrPA resulted in an inhibition rate of 72.44%, significantly higher than that in the control cells (P<0.05); treatment of the cells with 25, 50, 100, and 200 µmol/L 3-BrPA for 6 h resulted in intracellular adenosine triphosphate levels of 96.98%, 88.44%, 43.3% and 27.56% relative to the control level respectively. MCT1 can enhance the sensitivity of breast cancer cells to 3-BrPA possibly by transporting 3-BrPA into cells to inhibit cell glycolysis.

Highly sensitive detection of ESR1 mutations in cell-free DNA from patients with metastatic breast cancer using molecular barcode sequencing.

Science.gov (United States)

Masunaga, Nanae; Kagara, Naofumi; Motooka, Daisuke; Nakamura, Shota; Miyake, Tomohiro; Tanei, Tomonori; Naoi, Yasuto; Shimoda, Masafumi; Shimazu, Kenzo; Kim, Seung Jin; Noguchi, Shinzaburo

2018-01-01

We aimed to develop a highly sensitive method to detect ESR1 mutations in cell-free DNA (cfDNA) using next-generation sequencing with molecular barcode (MB-NGS) targeting the hotspot segment (c.1600-1713). The sensitivity of MB-NGS was tested using serially diluted ESR1 mutant DNA and then cfDNA samples from 34 patients with metastatic breast cancer were analyzed with MB-NGS. The results of MB-NGS were validated in comparison with conventional NGS and droplet digital PCR (ddPCR). MB-NGS showed a higher sensitivity (0.1%) than NGS without barcode (1%) by reducing background errors. Of the cfDNA samples from 34 patients with metastatic breast cancer, NGS without barcode revealed seven mutations in six patients (17.6%) and MB-NGS revealed six additional mutations including three mutations not reported in the COSMIC database of breast cancer, resulting in total 13 ESR1 mutations in ten patients (29.4%). Regarding the three hotspot mutations, all the patients with mutations detected by MB-NGS had identical mutations detected by droplet digital PCR (ddPCR), and mutant allele frequency correlated very well between both (r = 0.850, p < 0.01). Moreover, all the patients without these mutations by MB-NGS were found to have no mutations by ddPCR. In conclusion, MB-NGS could successfully detect ESR1 mutations in cfDNA with a higher sensitivity of 0.1% than conventional NGS and was considered as clinically useful as ddPCR.

H2Mab-77 is a Sensitive and Specific Anti-HER2 Monoclonal Antibody Against Breast Cancer.

Science.gov (United States)

Itai, Shunsuke; Fujii, Yuki; Kaneko, Mika K; Yamada, Shinji; Nakamura, Takuro; Yanaka, Miyuki; Saidoh, Noriko; Chang, Yao-Wen; Handa, Saori; Takahashi, Maki; Suzuki, Hiroyoshi; Harada, Hiroyuki; Kato, Yukinari

2017-08-01

Human epidermal growth factor receptor 2 (HER2) plays a critical role in the progression of breast cancers, and HER2 overexpression is associated with poor clinical outcomes. Trastuzumab is an anti-HER2 humanized antibody that leads to significant survival benefits in patients with HER2-positive metastatic breast cancers. In this study, we developed novel anti-HER2 monoclonal antibodies (mAbs) and characterized their efficacy in flow cytometry, Western blot, and immunohistochemical analyses. Initially, we expressed the full length or ectodomain of HER2 in LN229 glioblastoma cells and then immunized mice with ectodomain of HER2 or LN229/HER2, and performed the first screening by enzyme-linked immunosorbent assays using ectodomain of HER2. Subsequently, we selected mAbs according to their efficacy in flow cytometry (second screening), Western blot (third screening), and immunohistochemical analyses (fourth screening). Among 100 mAb clones, only three mAbs reacted with HER2 in Western blot, and clone H 2 Mab-77 (IgG 1 , kappa) was selected. Finally, immunohistochemical analyses with H 2 Mab-77 showed sensitive and specific reactions against breast cancer cells, warranting the use of H 2 Mab-77 to detect HER2 in pathological analyses of breast cancers.

Antiapoptotic Actions of Methyl Gallate on Neonatal Rat Cardiac Myocytes Exposed to H2O2

Directory of Open Access Journals (Sweden)

Sandhya Khurana

2014-01-01

Full Text Available Reactive oxygen species trigger cardiomyocyte cell death via increased oxidative stress and have been implicated in the pathogenesis of cardiovascular diseases. The prevention of cardiomyocyte apoptosis is a putative therapeutic target in cardioprotection. Polyphenol intake has been associated with reduced incidences of cardiovascular disease and better overall health. Polyphenols like epigallocatechin gallate (EGCG can reduce apoptosis of cardiomyocytes, resulting in better health outcomes in animal models of cardiac disorders. Here, we analyzed whether the antioxidant N-acetyl cysteine (NAC or polyphenols EGCG, gallic acid (GA or methyl gallate (MG can protect cardiomyocytes from cobalt or H2O2-induced stress. We demonstrate that MG can uphold viability of neonatal rat cardiomyocytes exposed to H2O2 by diminishing intracellular ROS, maintaining mitochondrial membrane potential, augmenting endogenous glutathione, and reducing apoptosis as evidenced by impaired Annexin V/PI staining, prevention of DNA fragmentation, and cleaved caspase-9 accumulation. These findings suggest a therapeutic value for MG in cardioprotection.

Antifungal Activity of Decyl Gallate against Several Species of Pathogenic Fungi

Directory of Open Access Journals (Sweden)

Ana Carolina Alves de Paula e Silva

2014-01-01

Full Text Available This work aims to demonstrate that the gallic acid structure modification to the decyl gallate (G14 compound contributed to increase the antifungal activity against several species of pathogenic fungi, mainly, Candida spp., Cryptococcus spp., Paracoccidioides spp., and Histoplasma capsulatum, according to standardized microdilution method described by Clinical Laboratory Standard Institute (CLSI documents. Moreover this compound has a particularly good selectivity index value, which makes it an excellent candidate for broad-spectrum antifungal prototype and encourages the continuation of subsequent studies for the discovery of its mechanism of action.

Radical chemistry of epigallocatechin gallate and its relevance to protein damage

DEFF Research Database (Denmark)

Hagerman, Ann E; Dean, Roger T; Davies, Michael Jonathan

2003-01-01

The radical chemistry of the plant polyphenolics epigallocatechin gallate (EGCG) and epigallocatechin (EGC) were investigated using electron paramagnetic resonance spectroscopy. Radical species formed spontaneously in aqueous solutions at low pH without external oxidant and were spin stabilized...... redox potentials of EGCG and EGC varied from 1000 mV at pH 3 to 400 mV at pH 8. The polyphenolics did not produce hydroxyl radicals unless reduced metal ions such as iron(II) were added to the system. Zinc(II)-stabilized EGCG radicals were more effective protein-precipitating agents than unoxidized EGCG...

Sensitivity of breast cancer cell lines to recombinant thiaminase I.

Science.gov (United States)

Liu, Shuqian; Monks, Noel R; Hanes, Jeremiah W; Begley, Tadhg P; Yu, Hui; Moscow, Jeffrey A

2010-05-01

We have previously shown that the expression of the thiamine transporter THTR2 is decreased sevenfold in breast cancer, which may leave breast cancer cells vulnerable to acute thiamine starvation. This concept was supported by the observation that MDA231 breast cancer xenografts demonstrated growth inhibition in mice fed a thiamine-free diet. We purified recombinant Bacillus thiaminolyticus thiaminase I enzyme, which digests thiamine, to study acute thiamine starvation in breast cancer. Thiaminase I enzyme was cytotoxic in six breast cancer cell lines with IC(50)s ranging from 0.012 to 0.022 U/ml. The growth inhibitory effects of the combination of thiaminase I with either doxorubicin or paclitaxel were also examined. Over a wide range of drug concentrations, thiaminase 1 was consistently synergistic or additive with doxorubicin and paclitaxel in MCF-7, ZR75, HS578T and T47D cell lines, with most combinations having a calculated combination index (CI) of less than 0.8, indicating synergy. Although thiaminase I exposure did not stimulate the energy-sensing signaling kinases AKT, AMPK and GSK-3beta in MCF-7, ZR75, HS578T and T47D cell lines, thiaminase I exposure did stimulate expression of the ER stress response protein GRP78. In summary, thiaminase I is cytotoxic in breast cancer cell lines and triggers the unfolded protein response. These findings suggest that THTR2 down-regulation in breast tumors may present a nutritional vulnerability that could be exploited by thiaminase I enzyme therapy.

Application of PET in breast cancer

International Nuclear Information System (INIS)

Noh, Dong Young

2002-01-01

Positron emission tomography (PET) is an imaging method that employs radionuclide and tomography techniques. Since 1995, we applied PET not only to the diagnosis of breast cancer but also to the detection of abnormalities in the augmented breast and to the detection of metastasis. Until 2001, we evaluated 242 breast cases by PET at PET center of Seoul National University Hospital. Our group has reported serially at the international journals. In the firtst report, PET showed high sensitivity for detecting breast cancer, both the primary and axillary node metastasis. A total of 27 patients underwent breast operations based on PET results at Seoul National University Hospital from 1995 to 1996. The diagnostic accuracy of PET were 97% for the primary tumor mass and 96% for axillary lymph node metastasis. In case of the breast augmented, PET also showed excellent diagnostic results for primary breast cancer and axillary lymph node metastasis where mammography and ultrasound could not diagnose properly. PET also had outstanding results in the detection of recurrent or metastatic breast cancer(sensitivity 94%, specificity 80%, accuracy 89%). In addition, our study gave some evidence that PET could be applied further to evaluate the growth rate of tumors by measuring SUV, and finally to prognosticated the disease. PET could also be applied to evaluate the response after chemotherapy to measure its metabolic rate and size. In conclsion, PET is a highly sensitive, accurate diagnostic tool for breast cancer of primary lesion in various conditions including metastasis

Studies on the Food Additive Propyl Gallate: Synthesis, Structural Characterization, and Evaluation of the Antioxidant Activity

Science.gov (United States)

Garrido, Jorge; Garrido, E. Manuela; Borges, Fernanda

2012-01-01

Antioxidants are additives largely used in industry for delaying, retarding, or preventing the development of oxidative deterioration. Propyl gallate (E310) is a phenolic antioxidant extensively used in the food, cosmetics, and pharmaceutical industries. A series of lab experiments have been developed to teach students about the importance and…

The origin of current blocking in interfacial conduction in Sr-doped lanthanum gallates

Science.gov (United States)

Park, Hee Jung

2018-02-01

The grain boundary transport of lanthanum gallate has been studied with various doping concentrations, and the origins of blocking on the grain boundary are compared. La1-xSrxGaO3 samples (x = 0.005, 0.01, 0.05 and 0.1) have been prepared and their bulk (grain) and grain boundary resistances been experimentally measured as a function of temperature (T: 200-550 °C) and oxygen partial pressure (Po2) using ac-impedance measurements. In addition, Hebb-Wagner polarization measurements have been conducted to investigate the electrical conductivity of minor charge carriers in the lanthanum gallates. The grain boundary resistance in the low-doped materials (x = 0.005 and 0.01) increases with increasing Po2 while in the highly-doped materials (x = 0.05, 0.1) it hardly depended on Po2. At lower concentrations conduction is mixed and at higher concentrations is found to be predominantly ionic conductivity. The space charge model successfully describes the mixed conduction at the grain boundary at low-doping, but does not explain the predominant ionic conductivity at high-doping. The origin of blocking at high-doping is explained by the crystallographic asymmetry of the grain boundary with respect to the bulk and/or Sr-segregation.

Novel Breast Imaging and Machine Learning: Predicting Breast Lesion Malignancy at Cone-Beam CT Using Machine Learning Techniques.

Science.gov (United States)

Uhlig, Johannes; Uhlig, Annemarie; Kunze, Meike; Beissbarth, Tim; Fischer, Uwe; Lotz, Joachim; Wienbeck, Susanne

2018-05-24

The purpose of this study is to evaluate the diagnostic performance of machine learning techniques for malignancy prediction at breast cone-beam CT (CBCT) and to compare them to human readers. Five machine learning techniques, including random forests, back propagation neural networks (BPN), extreme learning machines, support vector machines, and K-nearest neighbors, were used to train diagnostic models on a clinical breast CBCT dataset with internal validation by repeated 10-fold cross-validation. Two independent blinded human readers with profound experience in breast imaging and breast CBCT analyzed the same CBCT dataset. Diagnostic performance was compared using AUC, sensitivity, and specificity. The clinical dataset comprised 35 patients (American College of Radiology density type C and D breasts) with 81 suspicious breast lesions examined with contrast-enhanced breast CBCT. Forty-five lesions were histopathologically proven to be malignant. Among the machine learning techniques, BPNs provided the best diagnostic performance, with AUC of 0.91, sensitivity of 0.85, and specificity of 0.82. The diagnostic performance of the human readers was AUC of 0.84, sensitivity of 0.89, and specificity of 0.72 for reader 1 and AUC of 0.72, sensitivity of 0.71, and specificity of 0.67 for reader 2. AUC was significantly higher for BPN when compared with both reader 1 (p = 0.01) and reader 2 (p Machine learning techniques provide a high and robust diagnostic performance in the prediction of malignancy in breast lesions identified at CBCT. BPNs showed the best diagnostic performance, surpassing human readers in terms of AUC and specificity.

Antibacterial activity of epigallocatechin-3-gallate (EGCG) and its synergism with β-lactam antibiotics sensitizing carbapenem-associated multidrug resistant clinical isolates of Acinetobacter baumannii.

Science.gov (United States)

Lee, Spencer; Razqan, Ghaida Saleh Al; Kwon, Dong H

2017-01-15

Infections caused by Acinetobacter baumannii were responsive to conventional antibiotic therapy. However, recently, carbapenem-associated multidrug resistant isolates have been reported worldwide and present a major therapeutic challenge. Epigallocatechin-3-Gallate (EGCG) extracted from green tea exhibits antibacterial activity. We evaluated the antibacterial activity of EGCG and possible synergism with antibiotics in carbapenem-associated multidrug resistant A. baumannii. A potential mechanism for synergism was also explored. Seventy clinical isolates of A. baumannii collected from geographically different areas were analyzed by minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of EGCG. Checkerboard and time-killing assays were performed to exam the synergism between EGCG and antibiotics. The effects of EGCG on a multidrug efflux pump inhibitor (1-[1-naphthylmethyl] piperazine; NMP) and β-lactamase production were also examined in A. baumannii. Sixty-three of 70 clinical isolates of A. baumannii carried carbapenemase-encoding genes with carbapenem-associated multidrug resistance. Levels of MIC and MBC of EGCG ranged from 64 to 512µg/ml and from 128 to ≥1024µg/ml, respectively among the clinical isolates. MIC 90 and MBC 86 levels were 256µg/ml and 512µg/ml of EGCG, respectively. Subinhibitory concentration of EGCG in combination with all antibiotics tested, including carbapenem, sensitized (MICs fall≤1.0µg/ml) all carbapenem-associated multidrug resistant isolates. Checkerboard and time-killing assays showed synergism between EGCG and meropenem (or carbenicillin) counted as fractional inhibitory concentration of 2log10 within 12h, respectively. EGCG significantly increased the effect of NMP but was unrelated to β-lactamase production in A. baumannii, suggesting EGCG may be associated with inhibition of efflux pumps. Overall we suggest that EGCG-antibiotic combinations might provide an alternative approach to treat

Promising Ni-Fe-LSGMC anode compatible with lanthanum gallate electrolyte

Energy Technology Data Exchange (ETDEWEB)

Wang Shizhong [Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005 (China); School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0245 (United States)], E-mail: shizwang@sohu.com; He, Qiong [Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005 (China); Liu Meilin [School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0245 (United States)], E-mail: meilin.liu@mse.gatech.edu

2009-06-01

A number of composite materials in the Ni-Fe-LSGMC family have been studied as potential anodes for solid oxide fuel cells (SOFCs) based on strontium, magnesium, and cobalt doped lanthanum gallate electrolyte (LSGMC). The results show that Ni reacts with LSGMC especially under reducing conditions at high temperatures, resulting in high contact resistance, large electrode polarization, and poor performance. The reaction between Ni and LSGMC depends strongly on the composition and pre-sintering temperature of LSGMC, the concentration of iron in the electrode, and the processing and operating temperatures. Under proper conditions, Ni-Fe-LSGMC5 could be a promising high-performance anode with good compatibility with LSGMC5 electrolyte.

Promising Ni-Fe-LSGMC anode compatible with lanthanum gallate electrolyte

International Nuclear Information System (INIS)

Wang Shizhong; He, Qiong; Liu Meilin

2009-01-01

A number of composite materials in the Ni-Fe-LSGMC family have been studied as potential anodes for solid oxide fuel cells (SOFCs) based on strontium, magnesium, and cobalt doped lanthanum gallate electrolyte (LSGMC). The results show that Ni reacts with LSGMC especially under reducing conditions at high temperatures, resulting in high contact resistance, large electrode polarization, and poor performance. The reaction between Ni and LSGMC depends strongly on the composition and pre-sintering temperature of LSGMC, the concentration of iron in the electrode, and the processing and operating temperatures. Under proper conditions, Ni-Fe-LSGMC5 could be a promising high-performance anode with good compatibility with LSGMC5 electrolyte.

Metabolomics analysis reveals the metabolic and functional roles of flavonoids in light-sensitive tea leaves.

Science.gov (United States)

Zhang, Qunfeng; Liu, Meiya; Ruan, Jianyun

2017-03-20

As the predominant secondary metabolic pathway in tea plants, flavonoid biosynthesis increases with increasing temperature and illumination. However, the concentration of most flavonoids decreases greatly in light-sensitive tea leaves when they are exposed to light, which further improves tea quality. To reveal the metabolism and potential functions of flavonoids in tea leaves, a natural light-sensitive tea mutant (Huangjinya) cultivated under different light conditions was subjected to metabolomics analysis. The results showed that chlorotic tea leaves accumulated large amounts of flavonoids with ortho-dihydroxylated B-rings (e.g., catechin gallate, quercetin and its glycosides etc.), whereas total flavonoids (e.g., myricetrin glycoside, epigallocatechin gallate etc.) were considerably reduced, suggesting that the flavonoid components generated from different metabolic branches played different roles in tea leaves. Furthermore, the intracellular localization of flavonoids and the expression pattern of genes involved in secondary metabolic pathways indicate a potential photoprotective function of dihydroxylated flavonoids in light-sensitive tea leaves. Our results suggest that reactive oxygen species (ROS) scavenging and the antioxidation effects of flavonoids help chlorotic tea plants survive under high light stress, providing new evidence to clarify the functional roles of flavonoids, which accumulate to high levels in tea plants. Moreover, flavonoids with ortho-dihydroxylated B-rings played a greater role in photo-protection to improve the acclimatization of tea plants.

Metabolic interactions between cysteamine and epigallocatechin gallate.

Science.gov (United States)

Izzo, Valentina; Pietrocola, Federico; Sica, Valentina; Durand, Sylvère; Lachkar, Sylvie; Enot, David; Bravo-San Pedro, José Manuel; Chery, Alexis; Esposito, Speranza; Raia, Valeria; Maiuri, Luigi; Maiuri, Maria Chiara; Kroemer, Guido

2017-02-01

Phase II clinical trials indicate that the combination of cysteamine plus epigallocatechin gallate (EGCG) is effective against cystic fibrosis in patients bearing the most frequent etiological mutation (CFTRΔF508). Here, we investigated the interaction between both agents on cultured respiratory epithelia cells from normal and CFTRΔF508-mutated donors. We observed that the combination of both agents affected metabolic circuits (and in particular the tricarboxylic acid cycle) in a unique way and that cysteamine plus EGCG reduced cytoplasmic protein acetylation more than each of the 2 components alone. In a cell-free system, protein cross-linking activity of EGCG was suppressed by cysteamine. Finally, EGCG was able to enhance the conversion of cysteamine into taurine in metabolic flux experiments. Altogether, these results indicate that multiple pharmacological interactions occur between cysteamine and EGCG, suggesting that they contribute to the unique synergy of both agents in restoring the function of mutated CFTRΔF508.

Digital subtraction angiography for breast cancer

International Nuclear Information System (INIS)

Tsurumi, Kiyohiko; Okuyama, Nobuo

1987-01-01

We performed digital subtraction angiography (DSA) on 42 patients with breast diseases to investigate its efficiency. As a result we came to the following conclusions: 1. The sensitivity was well evaluated in intraarterial digital subtraction angiography (IA-DSA) of breast. 2. IA-DSA could diagnose difficult cases like cancer which had undergone augmentation mammoplasty, or like Paget's disease and others. 3. DSA was a safe examination method. 4. The sensitivity of IA-DSA of breast cancer is superior to intravenous digital subtraction angiography (IV-DSA). (author)

High resolution MRI of the breast at 3 T: which BI-RADS registered descriptors are most strongly associated with the diagnosis of breast cancer?

International Nuclear Information System (INIS)

Pinker-Domenig, K.; Helbich, T.H.; Bogner, W.; Gruber, S.; Bickel, H.; Duffy, S.; Schernthaner, M.; Dubsky, P.; Pluschnig, U.; Rudas, M.; Trattnig, S.

2012-01-01

To identify which breast lesion descriptors in the ACR BI-RADS registered MRI lexicon are most strongly associated with the diagnosis of breast cancer when performing breast MR imaging at 3 T. 150 patients underwent breast MR imaging at 3 T. Lesion size, morphology and enhancement kinetics were assessed according to the BI-RADS registered classification. Sensitivity, specificity and diagnostic accuracy were assessed. The effects of the BI-RADS registered descriptors on sensitivity and specificity were evaluated. Data were analysed using logistic regression. Histopathological diagnoses were used as the standard of reference. The sensitivity, specificity and diagnostic accuracy of breast MRI at 3 T was 99%, 81% and 93%, respectively. In univariate analysis, the final diagnosis of malignancy was positively associated with irregular shape (p registered breast lesion descriptors that are mostly strongly associated with breast cancer in breast MR imaging at 3 T are lesion shape, lesion margin, internal enhancement pattern and Type 3 enhancement kinetics. (orig.)

Contrast-enhanced spectral mammography (CESM) versus breast magnetic resonance imaging (MRI): A retrospective comparison in 66 breast lesions.

Science.gov (United States)

Li, L; Roth, R; Germaine, P; Ren, S; Lee, M; Hunter, K; Tinney, E; Liao, L

2017-02-01

The purpose of this study was to retrospectively compare the diagnostic performance of contrast-enhanced spectral mammography (CESM) with that of breast magnetic resonance imaging (BMRI) in breast cancer detection using parameters, including sensitivity, positive predictive value (PPV), lesion size, morphology, lesion and background enhancement, and examination time. A total of 48 women (mean age, 56years±10.6 [SD]) with breast lesions detected between October 2012 and March 2014 were included. Both CESM and BMRI were performed for each patient within 30 days. The enhancement intensity of lesions and breast background parenchyma was subjectively assessed for both modalities and was quantified for comparison. Statistical significance was analyzed using paired t-test for mean size of index lesions in all malignant breasts (an index lesion defined as the largest lesion in each breast), and a mean score of enhancement intensity for index lesions and breast background. PPV, sensitivity, and accuracy were calculated for both CESM and BMRI. The average duration time of CESM and MRI examinations was also compared. A total of 66 lesions were identified, including 62 malignant and 4 benign lesions. Both CESM and BMRI demonstrated a sensitivity of 100% for detection of breast cancer. There was no statistically significant difference between the mean size of index lesions (P=0.108). The enhancement intensity of breast background was significantly lower for CESM than for BMRI (P0.05). The average examination time for CESM was significantly shorter than that of BMRI (P<0.01). CESM has similar sensitivity than BMRI in breast cancer detection, with higher PPV and less background enhancement. CESM is associate with significantly shorter exam time thus a more accessible alternative to BMRI, and has the potential to play an important tool in breast cancer detection and staging. Copyright © 2016 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights

Vaporization and diffusion studies on the stability of doped lanthanum gallates

Energy Technology Data Exchange (ETDEWEB)

Stanislowski, M.; Singheiser, L.; Hilpert, K. [Research Center Juelich, Institute for Materials and Processes in Energy Systems, IWV-2, 52425 Juelich (Germany); Peck, D.H.; Woo, S.K. [Korea Institute of Energy Research, 71-2 Jang-Dong, Yuseong, 305-343 Daejeon (Korea); Schulz, O.; Martin, M. [RWTH Aachen University, Institute of Physical Chemistry, Landoltweg 2, 52056 Aachen (Germany)

2006-07-15

Vaporization and diffusion determine the stability of doped lanthanum gallates under SOFC operating conditions. Systematic vaporization studies of Ga and other elements were carried out using the vapor transpiration method. It was shown that the Ga vaporization is controlled by diffusion from the bulk to the surface. Diffusion coefficients D{sub Ga} and vaporization coefficients {alpha}{sub Ga} were determined by fitting the measured vaporization data to a vaporization model. Secondary phases formed as a result of the vaporization were detected. The influence of different doping levels of Sr, Mg and Fe on the Ga vaporization was elucidated. Moreover, cation self-diffusion of {sup 139}La, {sup 84}Sr and {sup 25}Mg as well as cation impurity diffusion of {sup 144}Nd, {sup 89}Y and {sup 56}Fe in polycrystalline samples of doped lanthanum gallate were directly determined for the composition La{sub 0.9}Sr{sub 0.1}Ga{sub 0.9}Mg{sub 0.1}O{sub 2.9} as an example, from diffusion profiles determined by SIMS. It was found that diffusion occurs by means of bulk and grain boundaries. The bulk diffusion coefficients are similar for all cations with activation energies which are strongly dependent on temperature. The results are explained by a frozen-in defect structure at low temperatures in the ABO{sub 3} perovskite lattice and by proposing a defect cluster containing cation vacancies in the A and B sublattices, as well as oxygen vacancies. (Abstract Copyright [2006], Wiley Periodicals, Inc.)

[Exploring a non-inflammatory clinical breast mass: Clinical practice guidelines].

Science.gov (United States)

Legendre, G; Guilhen, N; Nadeau, C; Brossard, A; Fauvet, R

2015-12-01

The aim of the study was to assess the diagnostic value of physical examination, radiologic explorations and percutaneous procedures of the breast in the exploration of a non-inflammatory palpable mass, in order to propose guidelines. A systematic literature review was conducted in the Medline and Cochrane library databases. International guidelines in French and English language were also consulted until April 30th 2015. Physical examination of a non-inflammatory palpable breast mass is not sufficient to eliminate a breast cancer (LE2). Mammography alone has a sensitivity between 70 and 95% for the diagnosis of breast cancer (LE3). Echography alone has a sensitivity of 98 to 100% for the diagnosis of breast cancer (LE2). The core needle biopsy has a better sensitivity and specificity than the fine-needle aspiration for breast cancer diagnosis (LE2). The association of mammography and 2D echography presents excellent sensitivity and negative predictive value (close to 100 %) to exclude a breast cancer (LE3). A double evaluation using mammography and echography is recommended in the exploration of a non-inflammatory palpable breast mass (grade B). Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Pressure pain sensitivity as a marker for stress and pressure pain sensitivity-guided stress management in women with primary breast cancer.

Science.gov (United States)

Axelsson, Christen K; Ballegaard, Søren; Karpatschof, Benny; Schousen, Peer

2014-08-01

To validate (1) Pressure Pain Sensitivity (PPS) as a marker for stress and (2) a PPS-guided intervention in women with primary Breast Cancer (BC). (1) A total of 58 women with BC were examined before and after 6 months of intervention. A control group of 165 women office employees was divided in a High Stress Group (HSG, n = 37) and a Low Stress Group (LSG, n = 128) to evaluate the association between PPS, questionnaire-related Quality of Life (QOL) and self-evaluated stress. (2) A PPS-guided stress management program (n = 40) was compared to a Psychosocial Group Intervention (PGI, n = 91) and no treatment (n = 86) with respect to a European Organization for Research and Treatment of Cancer (EORTC) questionnaire measured QOL. (1) Resting PPS and changes in PPS during the intervention period correlated significantly to EORTC and Short Form 36 (SF 36) main scores: (all p stress scores (all p stress. (2) The PPS-guided intervention group improved EORTC main score, pain and nausea, when compared to the control groups (all p stress. PPS-guided intervention improved QOL in women with breast cancer.

Hormone Therapy for Breast Cancer

Science.gov (United States)

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... sensitive breast cancer cells contain proteins called hormone receptors that become activated when hormones bind to them. ...

Breast-i Is an Effective and Reliable Adjunct Screening Tool for Detecting Early Tumour Related Angiogenesis of Breast Cancers in Low Resource Sub-Saharan Countries

Directory of Open Access Journals (Sweden)

Frank Naku Ghartey

2018-01-01

Full Text Available Background. What cheaper alternative breast screening procedures are available to younger women in addition to clinical breast examination (CBE in Sub-Saharan countries? In 2009, we first described BreastLight for screening and reported high sensitivity at detecting breast cancer. Due to limitations of BreastLight, we have since 2014 been using the more technologically advanced Breast-i to screen 2204 women to find cheaper screening alternatives. Methodology. First, the participant lies down for CBE and then, in a darkened room, Breast-i was placed underneath each breast and trained personnel confirm vein pattern and look out for dark spot(s to ascertain the presence of suspicious angiogenic lesion(s. Results. CBE detected 153 palpable breast masses and Breast-i, which detects angiogenesis, confirmed 136. However, Breast-i detected 22 more cases of which 7 had angiogenesis but were not palpable and 15 were missed by CBE due to large breast size. Overall confirmed cases were 26, with Breast-i detecting 7 cases missed by CBE. Breast-i and CBE gave sensitivities of 92.3% and 73%, respectively. Conclusion. Breast-i with its high sensitivity to angiogenesis, reliability, and affordability will be an effective adjunct detection device that can be used effectively to increase early detection in younger women, thereby increasing treatment success.

Biocatalytically Oligomerized Epicatechin with Potent and Specific Anti-proliferative Activity for Human Breast Cancer Cells

Directory of Open Access Journals (Sweden)

Ramaswamy Nagarajan

2008-11-01

Full Text Available Catechins, naturally occurring flavonoids derived from wine and green tea, are known to exhibit multiple health benefits. Epigallocatechin gallate (EGCG is one of the most widely investigated catechins, but its efficacy in cancer therapy is still inconsistent and limited. The poor stability of EGCG has contributed to the disparity in the reported anti-cancer activity and other beneficial properties. Here we report an innovative enzymatic strategy for the oligomerization of catechins (specifically epicatechin that yields stable, water-soluble oligomerized epicatechins with enhanced and highly specific anti-proliferative activity for human breast cancer cells. This one-pot oxidative oligomerization is carried out in ambient conditions using Horseradish Peroxidase (HRP as a catalyst yielding water-soluble oligo(epicatechins. The oligomerized epicatechins obtained exhibit excellent growth inhibitory effects against human breast cancer cells with greater specificity towards growth-inhibiting cancer cells as opposed to normal cells, achieving a high therapeutic differential. Our studies indicate that water-soluble oligomeric epicatechins surpass EGCG in stability, selectivity and efficacy at lower doses.

FDG-PET/CT detection of very early breast cancer in women with breast microcalcification lesions found in mammography screening

International Nuclear Information System (INIS)

Peng, Nang-Jing; Chou, Chen-Pin; Pan, Huay-Ben; Chang, Tsung-Hsien; Hu, Chin; Chiu, Yu-Li; Fu, Ting-Ying; Chang, Hong-Tai

2015-01-01

To assess the efficacy of positron emission tomography/computed tomography with the glucose analogue 2-[ 18 F]fluoro-2-deoxy-D-glucose (FDG-PET/CT) in Taiwanese women with early breast cancer detected by mammography screening. Dual-time-point imaging of whole-body supine and breast prone scans using FDG-PET/CT were performed sequentially in the pre-operative stage. A total of 11,849 patients underwent screening mammography, of whom 1,209 (10.2%) displayed positive results. After further investigation, 54 patients underwent FDG-PET/CT. Post-operative pathology examinations revealed malignancies in 26 lesions, including invasive breast cancer in 11 cases and non-invasive breast cancer in 15 cases, as well as benign disease in 30 lesions. The FDG-PET/CT findings from the whole-body scans were positive for 9 of 11 invasive breast cancers (81.8%) and 3 of 15 non-invasive cancers (20%), and they were negative for all benign lesions. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of FDG-PET/CT with whole-body supine imaging were 46.2%, 100%, 100% and 68.2%, respectively. Breast prone imaging revealed another patient with ductal carcinoma in situ, increasing the sensitivity to 50%. Importantly, positive PET findings were significantly correlated with tumour histology (P = 0.006), tumour size (P = 0.039) and Ki-67 expression (P = 0.011). FDG-PET/CT with whole-body scanning demonstrated high sensitivity to invasive breast cancer, limited sensitivity to non-invasive breast cancer, and high specificity for breast cancer. FDG-PET/CT might be useful for differentiating tumour invasiveness. However, the good PPV but poor NPV do not allow the physician to discard the biopsy.

Pressure pain sensitivity as a marker for stress and pressure pain sensitivity-guided stress management in women with primary breast cancer

DEFF Research Database (Denmark)

Axelsson, Christen K; Ballegaard, Søren; Karpatschof, Benny

2014-01-01

employees was divided in a High Stress Group (HSG, n = 37) and a Low Stress Group (LSG, n = 128) to evaluate the association between PPS, questionnaire-related Quality of Life (QOL) and self-evaluated stress. (2) A PPS-guided stress management program (n = 40) was compared to a Psychosocial Group......OBJECTIVES: To validate (1) Pressure Pain Sensitivity (PPS) as a marker for stress and (2) a PPS-guided intervention in women with primary Breast Cancer (BC). METHODS: (1) A total of 58 women with BC were examined before and after 6 months of intervention. A control group of 165 women office...... scores: (all p stress scores (all p

Partial Breast Irradiation Versus Whole Breast Radiotherapy for Early-Stage Breast Cancer: A Decision Analysis

International Nuclear Information System (INIS)

Sher, David J.; Wittenberg, Eve; Taghian, Alphonse G.; Bellon, Jennifer R.; Punglia, Rinaa S.

2008-01-01

Purpose: To compare the quality-adjusted life expectancy between women treated with partial breast irradiation (PBI) vs. whole breast radiotherapy (WBRT) for estrogen receptor-positive early-stage breast cancer. Methods and Materials: We developed a Markov model to describe health states in the 15 years after radiotherapy for estrogen receptor-positive early-stage breast cancer. Breast cancer recurrences were separated into local recurrences and elsewhere failures. Ipsilateral breast tumor recurrence (IBTR) risk was extracted from the Oxford overview, and rates and utilities were adapted from the literature. We studied two cohorts of women (aged 40 and 55 years), both of whom received adjuvant tamoxifen. Results: Assuming a no evidence of disease (NED)-PBI utility of 0.93, quality-adusted life expectancy after PBI (and WBRT) was 12.61 (12.57) and 12.10 (12.06) years for 40-year-old and 55-year-old women, respectively. The NED-PBI utility thresholds for preferring PBI over WBRT were 0.923 and 0.921 for 40-year-old and 55-year-old women, respectively, both slightly greater than the NED-WBRT utility. Outcomes were sensitive to the utility of NED-PBI, the PBI hazard ratio for local recurrence, the baseline IBTR risk, and the percentage of IBTRs that were local. Overall the degree of superiority of PBI over WBRT was greater for 55-year-old women than for 40-year-old women. Conclusions: For most utility values of the NED-PBI health state, PBI was the preferred treatment modality. This result was highly sensitive to patient preferences and was also dependent on patient age, PBI efficacy, IBTR risk, and the fraction of IBTRs that were local

Breast MRI in the Evaluation of Locally Recurrent or New Breast Cancer in the Postoperative Patient: Correlation of Morphology and Enhancement Features with the BI-RADS Category

International Nuclear Information System (INIS)

Seely, J.M.; Nguyen, E.T.; Jaffey, J.

2007-01-01

Background: While breast magnetic resonance imaging (MRI) is a highly sensitive test for detecting breast carcinoma, its specificity is lower, and several methods have been described on how to optimize specificity. Purpose: To compare the specificity and sensitivity of the BI-RADS category with the Fischer score in breast MRI for diagnosing cancer in women previously treated for breast cancer. Material and Methods: Women referred for evaluation of possible local recurrence or new breast cancer underwent breast MRI examination. Morphologic and kinetic enhancement characteristics were evaluated. BI-RADS category and Fischer score were assigned for each enhancing lesion and compared using a chi-square test. Sensitivity, specificity, and positive predictive values for 27 morphologic and enhancement characteristics were calculated. Pathologic diagnosis was obtained in all patients with enhancing lesions who had ultrasound or mammographic correlation. In those without correlate, 6-, 12-, and 24-month follow-up breast MRIs were obtained. Interobserver kappa correlation was determined for each variable studied. Results: 34 benign and 32 malignant lesions were identified in 26 of 30 patients. BI-RADS category yielded a specificity of 77.1% and a sensitivity of 81.8%. Fischer score had a lower specificity and sensitivity (62.9% and 72.7%, respectively) (P 100% enhancement was more sensitive than BI-RADS for malignant lesions. Specificity was highest for rim enhancement (97.1%), but sensitivity was low (24.2%). Interobserver kappa correlation was good for all 27 characteristics ( = 0.84), and highest for BI-RADS assessment ( 0.91). Conclusion: BI-RADS category in breast MRI had the highest combination of specificity and sensitivity, and the highest interobserver correlation. Fischer score and other morphologic and enhancement features lack sensitivity or specificity and do not have high positive predictive values when analyzed as single independent variables

How effective is mammography in detecting breast cancer recurrence in women after Breast Conservation Therapy (BCT) – A systematic literature review

International Nuclear Information System (INIS)

Curran, J.

2016-01-01

Breast Conservation Therapy (BCT) is now seen as the treatment of choice for early-stage breast cancer, leading to a rising demand for post-operative surveillance. Ongoing mammographic surveillance of the post-operative breast is necessary to minimise the morbidity risk from recurrence. This review evaluates the diagnostic value of mammography following BCT, and identifies the possible challenges with mammography regarding imaging, interpretation and test performance when investigating the treated breast. Relevant literature was reviewed and critically analysed. Three studies reported that surveillance mammography provided a significant survival advantage through early detection of recurrence. Five studies recognised the diagnostic challenges of surveillance mammography following BCT, reporting reduced sensitivity after breast surgery. The need for a more tailored screening strategy after treatment for breast cancer was highlighted in four studies. Although overall mammographic sensitivity is reduced after BCT, it is still proven to be effective in detecting recurrences, therefore remains an important surveillance tool. - Highlights: • Mammographic surveillance – survival advantage. • Sensitivity reduced post-surgery. • Tailored strategy needed.

MRI evaluation of the contralateral breast in patients with recently diagnosed breast cancer

International Nuclear Information System (INIS)

Taneja, Sangeeta; Jena, Amarnath; Zaidi, Syed Mohd. Shuaib; Khurana, Anuj

2012-01-01

Contralateral breast cancer can be synchronous and/or metachronous in patients with cancer of one breast. Detection of a synchronous breast cancer may affect patient management. Dynamic contrast-enhanced MRI of the breast (DCE-MRI) is a sensitive technique for detecting contralateral lesions occult on the other imaging modalities in women already diagnosed with cancer of one breast. The aim was to assess the incidence of mammographically occult synchronous contralateral breast cancer in patients undergoing MRI mammography for the evaluation of a malignant breast lesion. A total of 294 patients with recently diagnosed breast cancer who underwent MRI of the breast were evaluated for lesions in the opposite breast. The incidence of synchronous contralateral malignancy detected by preoperative MRI mammography done for evaluation of extent of disease was 4.1%. Preoperative breast MRI may detect clinically and mammographically occult synchronous contralateral cancer, and can help the patient avoid an additional second surgery or a second course of chemotherapy later; also, as theoretically these lesions are smaller, there may be a survival benefit as well

Inhibitory effects of epigallocatechin-3-gallate on cell proliferation and the expression of HIF-1α and P-gp in the human pancreatic carcinoma cell line PANC-1.

Science.gov (United States)

Zhu, Zhenni; Wang, Yu; Liu, Zhiqing; Wang, Fan; Zhao, Qiu

2012-05-01

The aim of this study was to verify the inhibitory effects of epigallocatechin-3-gallate (EGCG) on cell proliferation and the expression of hypoxia-inducible factor 1 (HIF-1α) and multidrug resistance protein 1 (MDR1/P-gp) in the human pancreatic carcinoma cell line PANC-1, thereby, reversing drug resistance of pancreatic carcinoma and improving its sensitivity to cancer chemotherapy. The human pancreatic carcinoma cell line PANC-1 was incubated under hypoxic conditions with different concentrations of epigallocatechin-3-gallate (EGCG) for indicated hours. The effects of EGCG on the mRNA or protein expression of HIF-1α and MDR1 were determined by RT-PCR or western blotting. Cellular proliferation and viability assays were measured using Cell Counting Kit-8. Western blotting revealed that EGCG inhibits the expression of the HIF-1α protein in a dose-dependent manner, while RT-PCR showed that it does not have any effects on HIF-1α mRNA. In addition, EGCG attenuated the mRNA and protein levels of P-gp in a dose-dependent manner, reaching a peak at the highest concentration. Furthermore, EGCG inhibited the proliferation of PANC-1 cells in a concentration- and time-dependent manner. The attenuation of HIF-1α and the consequently reduced P-gp could contribute to the inhibitory effects of EGCG on the proliferation of PANC-1 cells.

Retrospective observation on contribution and limitations of screening for breast cancer with mammography in Korea: detection rate of breast cancer and incidence rate of interval cancer of the breast.

Science.gov (United States)

Lee, Kunsei; Kim, Hyeongsu; Lee, Jung Hyun; Jeong, Hyoseon; Shin, Soon Ae; Han, Taehwa; Seo, Young Lan; Yoo, Youngbum; Nam, Sang Eun; Park, Jong Heon; Park, Yoo Mi

2016-11-18

The purpose of this study was to determine the benefits and limitations of screening for breast cancer using mammography. Descriptive design with follow-up was used in the study. Data from breast cancer screening and health insurance claim data were used. The study population consisted of all participants in breast cancer screening from 2009 to 2014. Crude detection rate, positive predictive value and sensitivity and specificity of breast cancer screening and, incidence rate of interval cancer of the breast were calculated. The crude detection rate of breast cancer screening per 100,000 participants increased from 126.3 in 2009 to 182.1 in 2014. The positive predictive value of breast cancer screening per 100,000 positives increased from 741.2 in 2009 to 1,367.9 in 2014. The incidence rate of interval cancer of the breast per 100,000 negatives increased from 51.7 in 2009 to 76.3 in 2014. The sensitivities of screening for breast cancer were 74.6% in 2009 and 75.1% in 2014 and the specificities were 83.1% in 2009 and 85.7% in 2014. To increase the detection rate of breast cancer by breast cancer screening using mammography, the participation rate should be higher and an environment where accurate mammography and reading can be performed and reinforcement of quality control are required. To reduce the incidence rate of interval cancer of the breast, it will be necessary to educate women after their 20s to perform self-examination of the breast once a month regardless of participation in screening for breast cancer.

Is breast compression associated with breast cancer detection and other early performance measures in a population-based breast cancer screening program?

Science.gov (United States)

Moshina, Nataliia; Sebuødegård, Sofie; Hofvind, Solveig

2017-06-01

We aimed to investigate early performance measures in a population-based breast cancer screening program stratified by compression force and pressure at the time of mammographic screening examination. Early performance measures included recall rate, rates of screen-detected and interval breast cancers, positive predictive value of recall (PPV), sensitivity, specificity, and histopathologic characteristics of screen-detected and interval breast cancers. Information on 261,641 mammographic examinations from 93,444 subsequently screened women was used for analyses. The study period was 2007-2015. Compression force and pressure were categorized using tertiles as low, medium, or high. χ 2 test, t tests, and test for trend were used to examine differences between early performance measures across categories of compression force and pressure. We applied generalized estimating equations to identify the odds ratios (OR) of screen-detected or interval breast cancer associated with compression force and pressure, adjusting for fibroglandular and/or breast volume and age. The recall rate decreased, while PPV and specificity increased with increasing compression force (p for trend screen-detected cancer, PPV, sensitivity, and specificity decreased with increasing compression pressure (p for trend breast cancer compared with low compression pressure (1.89; 95% CI 1.43-2.48). High compression force and low compression pressure were associated with more favorable early performance measures in the screening program.

Electronic Conductivity of Doped-Lanthanum Gallate Electrolytes

Science.gov (United States)

Yamaji, Katsuhiko; Xiong, Yue Ping; Kishimoto, Haruo; Horita, Teruhisa; Sakai, Natsuko; Brito, Manuel E.; Yokokawa, Harumi

Electronic conductivity of doped lanthanum gallate electrolytes were determined by using a Hebb-Wagner type polarization cell. Electronic conductivity of cobalt-doped, La0.8Sr0.2Ga0.8Mg0.15Co0.5O3-δ (LSGMC), and non cobalt-doped, La0.8Sr0.2Ga0.8Mg0.2O2.8 (LSGM8282), were measured as a function of oxygen partial pressures. The electronic conductivity of LSGM8282 showed a linear dependence on p(O2)1/4 in the higher p(O2) region, which is attributed to the electronic hole conductivity. The electronic conductivity of LSGMC showed a linear dependence on p(O2)1/6 in the higher p(O2) region. LSGMC has higher electronic conductivity than LSGM, and the conductivity was not clearly changed with temperatures between 600 and 800 °C. In lower p(O2) region, the electronic conductivity data have poor reproducibility and did not show any dependence on p(O2) because of the degradation of the electrolytes in severe reducing atmospheres.

Preparation and characterization of perovskite structure lanthanum gallate and lanthanum aluminate based oxides

OpenAIRE

Li, Shuai

2009-01-01

The present work was initiated to study the synthesis and properties of lanthanum gallate based oxides as intermediate temperature electrolyte for solid oxide fuel cells. The wet chemical method, polymer complexing route, was used to prepare the precursor powders. To further investigate the polymer complexing method, it was also applied to the preparation of lanthanum aluminate based oxides.   Single perovskite phase La0.8Sr0.2Ga0.83Mg0.17O2.815 can be prepared by the polymer complexing meth...

Breast cancer literacy and health beliefs related to breast cancer screening among American Indian women.

Science.gov (United States)

Roh, Soonhee; Burnette, Catherine E; Lee, Yeon-Shim; Jun, Jung Sim; Lee, Hee Yun; Lee, Kyoung Hag

2018-08-01

The purpose of this article is to examine the health beliefs and literacy about breast cancer and their relationship with breast cancer screening among American Indian (AI) women. Using the Health Belief Model (HBM) and hierarchical logistic regression with data from a sample of 286 AI female adults residing in the Northern Plains, we found that greater awareness of breast cancer screening was linked to breast cancer screening practices. However, perceived barriers, one of the HBM constructs, prevented such screening practices. This study suggested that culturally relevant HBM factors should be targeted when developing culturally sensitive breast cancer prevention efforts.

Green tea epigallocatechin-3-gallate modulates differentiation of naive CD4+ T cells into specific lineage effector cells

Science.gov (United States)

CD4+ T helper (Th) subsets Th1, Th9, and Th17 cells are implicated in inducing autoimmunity whereas regulatory T cells (Treg) have a protective effect. We previously showed that epigallocatechin-3-gallate (EGCG) attenuated experimental autoimmune encephalomyelitis (EAE) and altered CD4+ T cell subpo...

Performance of planar single cell lanthanum gallate based solid oxide fuel cells

Energy Technology Data Exchange (ETDEWEB)

Maffei, N.; Kuriakose, A.K. [Materials Technology Labs., CANMET, Natural Resources Canada, Ottawa, ON (Canada)

1998-09-01

A novel synthesis of high purity, single phase strontium-magnesium doped lanthanum gallate through a nitrate route is described. The prepared powder is formed into planar monolithic elements by uniaxial pressing followed by isostatic pressing and sintering. XRD analysis of the sintered elements reveal no detectable secondary phases. The performance of the electrolyte in solid oxide fuel cells (SOFC) with three different anode/cathode combinations tested at 700 C with respect to the J-V and power density is reported. The data show that the characteristics of this SOFC are strongly dependent on the particular anode/cathode system chosen. (orig.)

Performance of planar single cell lanthanum gallate based solid oxide fuel cells

Science.gov (United States)

Maffei, N.; Kuriakose, A. K.

A novel synthesis of high purity, single phase strontium-magnesium doped lanthanum gallate through a nitrate route is described. The prepared powder is formed into planar monolithic elements by uniaxial pressing followed by isostatic pressing and sintering. XRD analysis of the sintered elements reveal no detectable secondary phases. The performance of the electrolyte in solid oxide fuel cells (SOFC) with three different anode/cathode combinations tested at 700°C with respect to the J- V and power density is reported. The data show that the characteristics of this SOFC are strongly dependent on the particular anode/cathode system chosen.

Functional inhibition of Ubiquitin conjugating Enzyme (UBE2C) reduces proliferation and sensitizes cervical and breast cancer cells to radiation, doxorubicin, tamoxifen and letrozole

International Nuclear Information System (INIS)

Bose, Mayil Vahanan; Rawat, Akhilesh; Gopisetty, Gopal; Thangarajan, Rajkumar; Ganesharaja, Selvaluxmy

2014-01-01

Cervical cancer is the second most common cancer in women, worldwide. About 80% of cervical cancer cases occur in developing countries. Breast cancer has overtaken cervical cancer in most of the urban centers in India. In recent years, interest in the role of Ubiquitin conjugating Enzyme E2C (UBE2C) in cancer has shown a dramatic increase. Several studies have reported UBE2C as a potential oncogene and therapeutic target. The objective of the study was to elucidate radiation and chemo-sensitivity in response to functional inhibition of UBE2C in cervical and breast cancer cell lines. Taqman Real time PCR was performed to measure UBE2C levels in cervical and breast cancer cell lines. A dominant negative form of UBE2C (DN-UBE2C) was used to functionally inhibit wild type UBE2C. Cell proliferation and anchorage independent growth were measured by colorimetric assay and soft agar assay respectively. Radiation and chemo response of cell lines were assessed by colorimetric assay and clonogenic assay. Difference in sensitivity to radiation was observed among the cervical cancer cell lines studied. The growth rate of SiHa and HeLa transfected with DN- UBE2C was significantly reduced compared to vector control. Further, DN-UBE2C mediated radio-sensitivity was correlated with a significant decrease in resistance to radiation by SiHa and HeLa cells after transfection when compared to control cultures. Similarly, both the growth rate and the anchorage independent growth of MCF7 and MDAMB231 cells transfected with DN-UBE2C were significantly reduced compared to cells transfected with vector alone. MCF7 and MDAMB231 cells expressing DN-UBE2C were significantly more sensitive to different doses of radiation and doxorubicin compared to controls. In addition, DN-UBE2C transfected MCF7 cells were more sensitive to inhibition by tamoxifen and letrozole compared to vector controls. These results suggest that UBE2C can be used as a potential therapeutic target for cervical and breast

HPW-RX40 restores anoikis sensitivity of human breast cancer cells by inhibiting integrin/FAK signaling

Energy Technology Data Exchange (ETDEWEB)

Chen, I-Hua; Shih, Hsin-Chu [Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Hsieh, Pei-Wen [Graduate Institute of Natural Products, School of Traditional Chinese Medicine, and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan (China); Chang, Fang-Rong [Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan (China); Wu, Yang-Chang, E-mail: yachwu@mail.cmu.edu [School of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan (China); Wu, Chin-Chung, E-mail: ccwu@kmu.edu.tw [Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80708, Taiwan (China); Research Center for Natural Products and Drug Development, Kaohsiung Medical University, Kaohsiung, Taiwan (China)

2015-12-01

Anoikis is defined as apoptosis, which is induced by inappropriate cell–matrix interactions. Cancer cells with anoikis resistance tend to undergo metastasis, and this phenomenon has been reported to be associated with integrin and FAK activity. HPW-RX40 is a derivative of 3,4-methylenedioxy-β-nitrostyrene, which is known to prevent platelet aggregation by inhibition of integrin. In the present study, we investigated the effect of HPW-RX40 on an anoikis-resistant human breast cancer cell line MDA-MB-231. HPW-RX40 inhibited cell aggregation and induced cell death in suspending MDA-MB-231 cells, but had only little effect on the monolayer growth of adherent cells. Analysis of caspase activation and poly (ADP-ribose) polymerase (PARP) cleavage confirmed anoikis in HPW-RX40-treated suspending cancer cells. HPW-RX40 also affected the Bcl-2 family proteins in detached cancer cells. Furthermore, HPW-RX40 inhibited detachment-induced activation of FAK and the downstream phosphorylation of Src and paxillin, but did not affect this pathway in adherent cancer cells. We also found that the expression and activation of β1 integrin in MDA-MB-231 cells were reduced by HPW-RX40. The combination of HPW-RX40 with an EGFR inhibitor led to enhanced anoikis and inhibition of the FAK pathway in breast cancer cells. Taken together, our results suggest that HPW-RX40 restores the anoikis sensitivity in the metastatic breast cancer cells by inhibiting integrin and subsequent FAK activation, and reveal a potential strategy for prevention of tumor metastasis. - Highlights: • The β-nitrostyrene derivative, HPW-RX40, induces anoikis in human breast cancer cells. • HPW-RX40 inhibits the integrin/FAK signaling pathway. • The combination of HPW-RX40 with an EGFR inhibitor leads to enhanced anoikis. • HPW-RX40 may have a potential to prevent the spread of metastatic breast cancer.

HPW-RX40 restores anoikis sensitivity of human breast cancer cells by inhibiting integrin/FAK signaling

International Nuclear Information System (INIS)

Chen, I-Hua; Shih, Hsin-Chu; Hsieh, Pei-Wen; Chang, Fang-Rong; Wu, Yang-Chang; Wu, Chin-Chung

2015-01-01

Anoikis is defined as apoptosis, which is induced by inappropriate cell–matrix interactions. Cancer cells with anoikis resistance tend to undergo metastasis, and this phenomenon has been reported to be associated with integrin and FAK activity. HPW-RX40 is a derivative of 3,4-methylenedioxy-β-nitrostyrene, which is known to prevent platelet aggregation by inhibition of integrin. In the present study, we investigated the effect of HPW-RX40 on an anoikis-resistant human breast cancer cell line MDA-MB-231. HPW-RX40 inhibited cell aggregation and induced cell death in suspending MDA-MB-231 cells, but had only little effect on the monolayer growth of adherent cells. Analysis of caspase activation and poly (ADP-ribose) polymerase (PARP) cleavage confirmed anoikis in HPW-RX40-treated suspending cancer cells. HPW-RX40 also affected the Bcl-2 family proteins in detached cancer cells. Furthermore, HPW-RX40 inhibited detachment-induced activation of FAK and the downstream phosphorylation of Src and paxillin, but did not affect this pathway in adherent cancer cells. We also found that the expression and activation of β1 integrin in MDA-MB-231 cells were reduced by HPW-RX40. The combination of HPW-RX40 with an EGFR inhibitor led to enhanced anoikis and inhibition of the FAK pathway in breast cancer cells. Taken together, our results suggest that HPW-RX40 restores the anoikis sensitivity in the metastatic breast cancer cells by inhibiting integrin and subsequent FAK activation, and reveal a potential strategy for prevention of tumor metastasis. - Highlights: • The β-nitrostyrene derivative, HPW-RX40, induces anoikis in human breast cancer cells. • HPW-RX40 inhibits the integrin/FAK signaling pathway. • The combination of HPW-RX40 with an EGFR inhibitor leads to enhanced anoikis. • HPW-RX40 may have a potential to prevent the spread of metastatic breast cancer.

Sensitivity of the human breast to cancer induction by ionizing radiation

Energy Technology Data Exchange (ETDEWEB)

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

1978-06-01

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

Ribavirin restores ESR1 gene expression and tamoxifen sensitivity in ESR1 negative breast cancer cell lines

Directory of Open Access Journals (Sweden)

Sappok Anne

2011-12-01

Full Text Available Abstract Tumor growth is estrogen independent in approximately one-third of all breast cancers, which makes these patients unresponsive to hormonal treatment. This unresponsiveness to hormonal treatment may be explained through the absence of the estrogen receptor alpha (ESR1. The ESR1 gene re-expression through epigenetic modulators such as DNA methyltransferase inhibitors and/or histone deacetylase inhibitors restores tamoxifen sensitivity in ESR1 negative breast cancer cell lines and opens new treatment horizons in patients who were previously associated with a poor prognosis. In the study presented herein, we tested the ability of ribavirin, which shares some structural similarities with the DNA-methyltransferase inhibitor 5-azacytidine and which is widely known as an anti-viral agent in the treatment of hepatitis C, to restore ESR1 gene re-expression in ESR1 negative breast cancer cell lines. In our study we identified ribavirin to restore ESR1 gene re-expression alone and even more in combination with suberoylanilide hydroxamic acid (SAHA - up to 276 fold induction. Ribavirin and analogs could pave the way to novel translational research projects that aim to restore ESR1 gene re-expression and thus the susceptibility to tamoxifen-based endocrine treatment strategies.

Annual Screening Mammogram and its Relation to Breast Density

Directory of Open Access Journals (Sweden)

Sabek EAS

2017-11-01

Full Text Available Background: Current national screening programs totally depend on mammographic evaluation. After increased incidence of breast cancer in women under the age of 35, mammography sensitivity in now a question. Several factors added to decrease sensitivity of mammography, such as increased density in older age groups and increased aggressiveness of tumour biology. All these factors will change the reliability of the screening program. The study is a retrospective study conducted at Ain Shams University. Method: 138 patients diagnosed with cancer breast underwent both mammography and sonography to determine percentage of patient with more than one focus, age and density distribution breast cancer in the affected patient and accuracy of both mammography and US. Results: By studying this population, we found that around 61,44% have areas of density ranging from dense breast, heterogenous density or scattered density. These areas of density render the mammography a less sensitive tool as its sensitivity fall to 34.09%, while that of US was 77.27%. Conclusion: As breast cancer is prevalent in younger population, also with increased density in older population who are relatively insensitive to mammography, we recommended the use of Automated Breast Ultrasound (ABUS in the national screening program.

Fabrication and functionalization of magnesium nanoparticle for lipase immobilization in n-propyl gallate synthesis

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Abhishek Sharma

2017-10-01

Full Text Available An extracellular lipase partially purified from Bacillus thermoamylovorans BHK67 was effectively immobilized onto modified magnetic MgFe2O4 nanoparticles (NPs. NPs were prepared by the sol-gel auto-combustion method and characterized by Fourier transform infrared (FTIR spectroscopy, X-ray diffraction (XRD, Ultra-Violet–Visible Spectroscopy (UV–vis and atomic force microscopy (AFM. Protein loading reached a saturated amount of about 0.20 mg lipase per milligram of MgFe2O4 NPs with 78.9% binding efficiency. The NPs-bound lipase also showed stability following exposure to n-propanol and iso-propanol or FeCl2 and MgCl2 metal ions at (1 mM at 55 °C. NPs-bound lipase also retained 50% of its original hydrolytic activity even after 8th cycle, as well as after 12 h of incubation at 55 °C. NPs-bound lipase in an esterification reaction of n-propanol and gallic acid (25 mM performed for 12 h at 55 °C produced n-propyl gallate with a conversion rate of 82%. Synthesized n-propyl gallate possessed strong antioxidant activity, which was confirmed by DPPH assay, and in addition has anticancerous activity which was tested on a human L132 cell line.

Breast cancer screening

International Nuclear Information System (INIS)

Vandenbroucke, A.

1987-01-01

Many studies have shown that breast cancer screening is able to reduce breast cancer mortality, including the HIP study, the Swedish Trial and the Netherlands studies. Mammography is considered as the most effective method for breast cancer screening but it might be unfeasible for some reasons: - the population acceptability of the method might be low. Indeed, most populations of the South of Europe are less compliant to mass screening than populations of the North of Europe; - the medical equipment and personnel - radiologists and pathologists - might be insufficient; - it might be too costly for the National Health Service, specially where the incidence rate of breast cancer is relatively low (i.e. Greece, Portugal). The validity of screening tests is judged by their sensitivity and their specificity

Bioactivity-guided fractionation of an antidiarrheal Chinese herb Rhodiola kirilowii (Regel) Maxim reveals (-)-epicatechin-3-gallate and (-)-epigallocatechin-3-gallate as inhibitors of cystic fibrosis transmembrane conductance regulator.

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Chen, Lei; Yu, Bo; Zhang, Yaofang; Gao, Xin; Zhu, Liang; Ma, Tonghui; Yang, Hong

2015-01-01

Cystic fibrosis transmembrane conductance regulator (CFTR) is the principal apical route for transepithelial fluid transport induced by enterotoxin. Inhibition of CFTR has been confirmed as a pharmaceutical approach for the treatment of secretory diarrhea. Many traditional Chinese herbal medicines, like Rhodiola kirilowii (Regel) Maxim, have long been used for the treatment of secretory diarrhea. However, the active ingredients responsible for their therapeutic effectiveness remain unknown. The purpose of this study is to identify CFTR inhibitors from Rhodiola kirilowii (Regel) Maxim via bioactivity-directed isolation strategy. We first identified fractions of Rhodiola kirilowii (Regel) Maxim that inhibited CFTR Cl- channel activity. Further bioactivity-directed fractionation led to the identification of (-)-epigallocatechin-3-gallate (EGCG) as CFTR Cl- channel inhibitor. Analysis of 5 commercially available EGCG analogs including (+)-catechins (C), (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin-3-gallate (ECG) and EGCG revealed that ECG also had CFTR inhibitory activity. EGCG dose-dependently and reversibly inhibited CFTR Cl- channel activity in transfected FRT cells with an IC50 value around 100 μM. In ex vivo studies, EGCG and ECG inhibited CFTR-mediated short-circuit currents in isolated rat colonic mucosa in a dose-dependent manner. In an intestinal closed-loop model in mice, intraluminal application of EGCG (10 μg) and ECG (10 μg) significantly reduced cholera toxin-induced intestinal fluid secretion. CFTR Cl- channel is a molecular target of natural compounds EGCG and ECG. CFTR inhibition may account, at least in part, for the antidiarrheal activity of Rhodiola kirilowii (Regel) Maxim. EGCG and ECG could be new lead compounds for development of CFTR-related diseases such as secretory diarrhea.

Skin Protective Effect of Epigallocatechin Gallate

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Eunji Kim

2018-01-01

Full Text Available Epigallocatechin gallate (EGCG is a catechin and an abundant polyphenol in green tea. Although several papers have evaluated EGCG as a cosmetic constituent, the skin hydration effect of EGCG is poorly understood. We aimed to investigate the mechanism by which EGCG promotes skin hydration by measuring hyaluronic acid synthase (HAS and hyaluronidase (HYAL gene expression and antioxidant and anti-pigmentation properties using cell proliferation assay, Western blotting analysis, luciferase assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH assay, and reverse transcription polymerase chain reaction (RT-PCR analysis. RT-PCR showed that EGCG increased the expression of natural moisturizing factor-related genes filaggrin (FLG, transglutaminase-1, HAS-1, and HAS-2. Under UVB irradiation conditions, the expression level of HYAL was decreased in HaCaT cells. Furthermore, we confirmed the antioxidant activity of EGCG and also showed a preventive effect against radical-evoked apoptosis by downregulation of caspase-8 and -3 in HaCaT cells. EGCG reduced melanin secretion and production in melanoma cells. Together, these results suggest that EGCG might be used as a cosmetic ingredient with positive effects on skin hydration, moisture retention, and wrinkle formation, in addition to radical scavenging activity and reduction of melanin generation.

Exemestane in early breast cancer: a review

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Michael Untch

2008-12-01

Full Text Available Michael Untch1, Christian Jackisch21Interdisciplinary Breast Centre, Helios Klinikum Berlin-Buch, University Charité, Berlin, Germany; 2Department of Gynecology/Obstetrics, Klinikum Offenbach GmbH, Offenbach, GermanyAbstract: The adjuvant treatment of women with endocrine-sensitive early breast cancer has been dominated for the last 40 years by tamoxifen. However, the side-effects associated with this therapy have prompted a search for safer and biochemically more selective endocrine agents and led to the development of the third-generation aromatase inhibitors (AIs anastrozole, letrozole and exemestane. Promising results in advanced disease have paved the way for treating early breast cancer, and AIs are increasingly replacing tamoxifen in the adjuvant setting. Several large, randomized trials with AIs have been completed or are ongoing in women with early-stage breast cancer, documenting the significant impact that these drugs are making on the risk for recurrence of breast cancer. As a result, there is increasing and widespread use of AI therapy for the treatment of early-stage endocrine-responsive breast cancer. This review summarizes the data for exemestane in the adjuvant setting, showing that a switch to exemestane after 2 to 3 years of tamoxifen therapy is associated with a statistically significant survival benefit and is regarded as being sensitive by international and national experts.Keywords: early breast cancer, adjuvant setting, endocrine-sensitive, tamoxifen, aromatase inhibitor, exemestane, switch, IES 31, NSABP B-33, TEAM

Abbreviated MRI protocols for detecting breast cancer in women with dense breasts

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Chen, Shung Qing; Huang, Min; Shen, Yu Ying; Liu, Chen Lu; Xu, Chuan Xiao [The Affiliated Suzhou Hospital, Nanjing Medical University, Suzhou (China)

2017-06-15

To evaluate the validity of two abbreviated protocols (AP) of MRI in breast cancer screening of dense breast tissue. This was a retrospective study in 356 participants with dense breast tissue and negative mammography results. The study was approved by the Nanjing Medical University Ethics Committee. Patients were imaged with a full diagnostic protocol (FDP) of MRI. Two APs (AP-1 consisting of the first post-contrast subtracted [FAST] and maximum-intensity projection [MIP] images, and AP-2 consisting of AP-1 combined with diffusion-weighted imaging [DWI]) and FDP images were analyzed separately, and the sensitivities and specificities of breast cancer detection were calculated. Of the 356 women, 67 lesions were detected in 67 women (18.8%) by standard MR protocol, and histological examination revealed 14 malignant lesions and 53 benign lesions. The average interpretation time of AP-1 and AP-2 were 37 seconds and 54 seconds, respectively, while the average interpretation time of the FDP was 3 minutes and 25 seconds. The sensitivities of the AP-1, AP-2, and FDP were 92.9, 100, and 100%, respectively, and the specificities of the three MR protocols were 86.5, 95.0, and 96.8%, respectively. There was no significant difference among the three MR protocols in the diagnosis of breast cancer (p > 0.05). However, the specificity of AP-1 was significantly lower than that of AP-2 (p = 0.031) and FDP (p = 0.035), while there was no difference between AP-2 and FDP (p > 0.05). The AP may be efficient in the breast cancer screening of dense breast tissue. FAST and MIP images combined with DWI of MRI are helpful to improve the specificity of breast cancer detection.

Inhibitory effects of polyphenol-enriched extract from Ziyang tea against human breast cancer MCF-7 cells through reactive oxygen species-dependent mitochondria molecular mechanism

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Wenfeng Li

2016-07-01

Full Text Available A polyphenol-enriched extract from selenium-enriched Ziyang green tea (ZTP was selected to evaluate its antitumor effects against human breast cancer MCF-7 cells. In ZTP, (−-epigallocatechin gallate (28.2% was identified as the major catechin, followed by (−-epigallocatechin (5.7% and (−-epicatechin gallate (12.6%. ZTP was shown to inhibit MCF-7 cell proliferation (half maximal inhibitory concentration, IC50 = 172.2 μg/mL by blocking cell-cycle progression at the G0/G1 phase and inducing apoptotic death. Western blotting assay indicated that ZTP induced cell-cycle arrest by upregulation of p53 and reduced the expression of CDK2 in MCF-7 cells. ZTP-caused cell apoptosis was associated with an increase in Bax/Bcl-2 ratio, and activation of caspase-3 and -9. MCF-7 cells treated with ZTP also showed an overproduction of reactive oxygen species, suggesting that reactive oxygen species played an important role in the induction of apoptosis in MCF-7 cells. This is the first report showing that ZTP is a potential novel dietary agent for cancer chemoprevention or chemotherapy.

PET in management of breast cancer

International Nuclear Information System (INIS)

Lee, Myung-Chul

2004-01-01

Full text: PET provides useful information about tumor metabolism enabling accurate visualization of malignant lesions. Approximately 60-80% suspicious lesions on mammography have benign histology and about 10% of breast cancers with palpable mass are not identified in mammography. The key roles of PET technology in breast cancer are in: primary diagnosis, staging, recurrent diseases monitoring and prediction of therapy response. The sensitivity and specificity of FDG-PET for the diagnosis of breast cancer has been reported to be 68-100% and 83-100%, respectively. Considering the increasing number of small breast tumors detected by mammography and false negative results, the clinical relevance of FDG-PET for the primary diagnosis is limited. In selected patients, however, for example with dense breasts, breasts implants, augmented breast or after breast surgery, which can affect the accuracy of mammography, and in cases with equivocal mammography, FDG-PET can provide clinically relevant information. PET accurately determines the extent of disease, including the loco-regional lymph node status. Furthermore, whole-body PET imaging promises a high diagnostic accuracy for detecting recurrent or metastatic breast carcinoma with a high positive predictive value. We studied the usefulness of the FDG-PET in 42 preoperative patients with suspected breast cancer in differentiation of lesions. The diagnostic value of FDG-PET in terms of sensitivity and specificity was 95% and 77% respectively in primary mass while it was 73% and 100% for axillary lymph nodes. PET is much more accurate than other conventional modalities. The sensitivity of FDG-PET for correct staging of axillary nodal status is 84-100%. It has the potential to replace conventional procedures for the staging of distant metastases. We observed the sensitivity and the specificity of FDG-PET to be 96% and 85% to detect distant metastases. FDG-PET may become the method of choice for the early assessment of

Evaluation of breast parenchymal density with QUANTRA software

International Nuclear Information System (INIS)

Pahwa, Shivani; Hari, Smriti; Thulkar, Sanjay; Angraal, Suveen

2015-01-01

To evaluate breast parenchymal density using QUANTRA software and to correlate numerical breast density values obtained from QUANTRA with ACR BI-RADS breast density categories. Two-view digital mammograms of 545 consecutive women (mean age - 47.7 years) were categorized visually by three independent radiologists into one of the four ACR BI-RADS categories (D1-D4). Numerical breast density values as obtained by QUANTRA software were then used to establish the cutoff values for each category using receiver operator characteristic (ROC) analysis. Numerical breast density values obtained by QUANTRA (range - 7-42%) were systematically lower than visual estimates. QUANTRA breast density value of less than 14.5% could accurately differentiate category D1 from the categories D2, D3, and D4 [area under curve (AUC) on ROC analysis - 94.09%, sensitivity - 85.71%, specificity - 84.21%]. QUANTRA density values of <19.5% accurately differentiated categories D1 and D2 from D3 and D4 (AUC - 94.4%, sensitivity - 87.50%, specificity - 84.60%); QUANTRA density values of <26.5% accurately differentiated categories D1, D2, and D3 from category D4 (AUC - 90.75%, sensitivity - 88.89%, specificity - 88.621%). Breast density values obtained by QUANTRA software can be used to obtain objective cutoff values for each ACR BI-RADS breast density category. Although the numerical density values obtained by QUANTRA are lower than visual estimates, they correlate well with the BI-RADS breast density categories assigned visually to the mammograms

Breast cancer screening: Evidence of the effect of adjunct ultrasound screening in women with unilateral mammography-negative dense breasts

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Atoosa Adibi

2015-01-01

Full Text Available Background: Patients with the previous history of breast cancer are in risk of contralateral breast cancer. On the other hand, increased breast density is a risk factor for breast cancer and the sensitivity of detecting nonpalpable cancers in screening mammography in radiographically dense breasts is low. The use of ultrasonography in dense breast remains a controversial topic. The purpose of this study was to assess the usefulness of routine ultrasonography in follow-up of women with the previous history of breast cancer and negative mammography but dense breasts. Materials and Methods: In a cross-sectional study, a total of 267 individuals with unilateral postmastectomy mammogram screened and 153 subjects assigned to study. There were 28 subjects with American College of Radiology (ACR breast density 2 and 125 with ACR breast density 3-4, which there was no new finding in their mammogram in comparison to previous studies. We assumed subjects with ACR breast density 3-4 as mammographic Breast Imaging Reporting and Data System (BI-RADS category 0 for malignancy. Standard two-view mammogram was performed for all participants, and breast ultrasound (US examinations were performed by an expert radiologist in radial and anti-radial planes. The data were analyzed using SPSS version 20.0 (SPSS Inc., Chicago, Illinois, USA. Results: The results showed that in subjects with ACR breast density 3-4, when there was no new density in two consecutive mammograms in comparison to previous studies, US also showed no possibility for malignancy (BI-RADS 1-2. And also in subjects with ACR breast density 2, when the mammographic results were BI-RADS 1-2, the US results was the same. Conclusion: Our data indicate that for the detection of breast cancer, sensitivity of US was not greater than mammography in patients with postmastectomy unilateral dense breast if there is not any new density.

Propyl gallate synthesis using acidophilic tannase and simultaneous production of tannase and gallic acid by marine Aspergillus awamori BTMFW032.

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Beena, P S; Basheer, Soorej M; Bhat, Sarita G; Bahkali, Ali H; Chandrasekaran, M

2011-07-01

Marine Aspergillus awamori BTMFW032, recently reported by us, produce acidophilic tannase as extracellular enzyme. Here, we report the application of this enzyme for synthesis of propyl gallate by direct transesterification of tannic acid and in tea cream solubilisation besides the simultaneous production of gallic acid along with tannase under submerged fermentation by this fungus. This acidophilic tannase enabled synthesis of propyl gallate by direct transesterification of tannic acid using propanol as organic reaction media under low water conditions. The identity of the product was confirmed with thin layer chromatography and Fourier transform infrared spectroscopy. It was noted that 699 U/ml of enzyme could give 60% solubilisation of tea cream within 1 h. Enzyme production medium was optimized adopting Box-Behnken design for simultaneous synthesis of tannase and gallic acid. Process variables including tannic acid, sodium chloride, ferrous sulphate, dipotassium hydrogen phosphate, incubation period and agitation were recognized as the critical factors that influenced tannase and gallic acid production. The model obtained predicted 4,824.61 U/ml of tannase and 136.206 μg/ml gallic acid after 48 h of incubation, whereas optimized medium supported 5,085 U/ml tannase and 372.6 μg/ml of gallic acid production after 36 and 84 h of incubation, respectively, with a 15-fold increase in both enzyme and gallic acid production. Results indicated scope for utilization of this acidophilic tannase for transesterification of tannic acid into propyl gallate, tea cream solubilisation and simultaneous production of gallic acid along with tannase.

Study of the Effect on Ionic Conductivity and Structral Morphology of the SR Doped Lanthanum Gallate Solid Electrolyte

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Sood, Kapil; Singh, K.; Pandey, O. P.

2013-07-01

In the present study, lanthanum gallate and Sr-doped lanthanum gallate samples were prepared by conventional solid state reaction method. The phase conformation has been performed by using X-ray diffraction (XRD) study. The elemental composition has been confirmed using energy dispersive spectroscopy (EDS) analysis. Ac conductivity of the samples has been measured in the frequency range 0.1-106 Hz and from 50-800 °C. The impedance plots among real and complex impedances at particular temperature have been discussed. The behavior shows the effect of bulk and grain boundary effects of the doped sample. The impedance plots with frequency have been analyzed. The plots have been well fitted to equivalent circuit model. The conductivity shows the Arrhenius type of behavior. The activation energy has been calculated from the plots and represents that the conductivity through the material is mainly ionic. The structural morphology of the samples has been investigated using scanning electron microscope (SEM). The micrograph shows that the porosity and grain size both decreases with Sr-doping.

Comparison of CA15-3 and CEA in breast cancer

International Nuclear Information System (INIS)

Rajkovaca, Z.; Mijatovic, J.; Matavulj, A.; Kovacevic, P.; Ponorac, N.

2002-01-01

Aim: Tumor markers are potentially powerful means for obtaining information about cancers whilst causing minimal morbidity, inconvenience and cost. CA 15-3 and CEA are considered useful tumor markers in monitoring breast cancer patients. The aim of this study was to evaluate which of these two markers are in better correlate with the disease in patients surgically treated for breast cancer. Material and Methods: We retrospectively reviewed values of CA15-3 and CEA in 342 patients (median age 52.18 years, range 27-78 years) with surgically treated and pathologically proven breast cancer. CA15-3 and CEA was measured by radioimmunoassay. CA15-3 levels above 30 U/ml and CEA levels above 5 ng/ml were considered as positive values. Results: Out of 342 patients, 86 had elevated CA15-3 levels (sensitivity: 25.1%) and 68 of 342 patients had positive CEA levels (sensitivity 19.9%). Two hundred thirty seven (237) of the patients suffering from breast cancer (69.3%) did not have metastatic disease. In this group CA15-3 sensitivity was 94.5%, while CEA sensitivity was 87.3%. One hundred and five (105) patients (30.7%) had metastatic disease. In this group, CA15-3 sensitivity was 69.5% and CEA sensitivity was 36.2% (P < 0.05). With regard to the correlation of the two tumor markers with clinical course patients had significantly higher levels of CA15-3 than of CEA in metastatic breast cancer. Conclusion: This result suggests CA15-3 to be the more sensitive and more specific of the two tumor markers for metastatic breast cancer detection and monitoring

Circulating microRNAs in breast cancer

DEFF Research Database (Denmark)

Hamam, Rimi; Hamam, Dana; Alsaleh, Khalid A

2017-01-01

Effective management of breast cancer depends on early diagnosis and proper monitoring of patients' response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence in ...... circulating miRNAs as diagnostic, prognostic or predictive biomarkers in breast cancer management.......Effective management of breast cancer depends on early diagnosis and proper monitoring of patients' response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence...... in the past several years has highlighted the potential use of peripheral blood circulating nucleic acids such as DNA, mRNA and micro (mi)RNA in breast cancer diagnosis, prognosis and for monitoring response to anticancer therapy. Among these, circulating miRNA is increasingly recognized as a promising...

Epigallocatechin Gallate Nanodelivery Systems for Cancer Therapy

Directory of Open Access Journals (Sweden)

Andreia Granja

2016-05-01

Full Text Available Cancer is one of the leading causes of morbidity and mortality all over the world. Conventional treatments, such as chemotherapy, are generally expensive, highly toxic and lack efficiency. Cancer chemoprevention using phytochemicals is emerging as a promising approach for the treatment of early carcinogenic processes. (−-Epigallocatechin-3-gallate (EGCG is the major bioactive constituent in green tea with numerous health benefits including anti-cancer activity, which has been intensively studied. Besides its potential for chemoprevention, EGCG has also been shown to synergize with common anti-cancer agents, which makes it a suitable adjuvant in chemotherapy. However, limitations in terms of stability and bioavailability have hampered its application in clinical settings. Nanotechnology may have an important role in improving the pharmacokinetic and pharmacodynamics of EGCG. Indeed, several studies have already reported the use of nanoparticles as delivery vehicles of EGCG for cancer therapy. The aim of this article is to discuss the EGCG molecule and its associated health benefits, particularly its anti-cancer activity and provide an overview of the studies that have employed nanotechnology strategies to enhance EGCG’s properties and potentiate its anti-tumoral activity.

Early Diagnosis of Breast Cancer.

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Wang, Lulu

2017-07-05

Early-stage cancer detection could reduce breast cancer death rates significantly in the long-term. The most critical point for best prognosis is to identify early-stage cancer cells. Investigators have studied many breast diagnostic approaches, including mammography, magnetic resonance imaging, ultrasound, computerized tomography, positron emission tomography and biopsy. However, these techniques have some limitations such as being expensive, time consuming and not suitable for young women. Developing a high-sensitive and rapid early-stage breast cancer diagnostic method is urgent. In recent years, investigators have paid their attention in the development of biosensors to detect breast cancer using different biomarkers. Apart from biosensors and biomarkers, microwave imaging techniques have also been intensely studied as a promising diagnostic tool for rapid and cost-effective early-stage breast cancer detection. This paper aims to provide an overview on recent important achievements in breast screening methods (particularly on microwave imaging) and breast biomarkers along with biosensors for rapidly diagnosing breast cancer.

Combination of ascorbate/epigallocatechin-3-gallate/gemcitabine synergistically induces cell cycle deregulation and apoptosis in mesothelioma cells

Energy Technology Data Exchange (ETDEWEB)

Martinotti, Simona [Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale “Amedeo Avogadro”, viale T. Michel 11, 15121 Alessandria (Italy); Ranzato, Elia, E-mail: ranzato@unipmn.it [Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale “Amedeo Avogadro”, viale T. Michel 11, 15121 Alessandria (Italy); Parodi, Monica [IRCCS A.O.U. S. Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, 16132 Genova (Italy); DI.ME.S., Università degli Studi di Genova, Via L. Alberti 2, 16132 Genova (Italy); Vitale, Massimo [IRCCS A.O.U. S. Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, 16132 Genova (Italy); Burlando, Bruno [Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale “Amedeo Avogadro”, viale T. Michel 11, 15121 Alessandria (Italy)

2014-01-01

Malignant mesothelioma (MMe) is a poor-prognosis tumor in need of innovative therapies. In a previous in vivo study, we showed synergistic anti-MMe properties of the ascorbate/epigallocatechin-3-gallate/gemcitabine combination. We have now focused on the mechanism of action, showing the induction of apoptosis and cell cycle arrest through measurements of caspase 3, intracellular Ca{sup 2+}, annexin V, and DNA content. StellArray™ PCR technology and Western immunoblotting revealed DAPK2-dependent apoptosis, upregulation of cell cycle promoters, downregulation of cell cycle checkpoints and repression of NFκB expression. The complex of data indicates that the mixture is synergistic in inducing cell cycle deregulation and non-inflammatory apoptosis, suggesting its possible use in MMe treatment. - Highlights: • Ascorbate/epigallocathechin-gallate/gemcitabine has been tested on mesothelioma cells • A synergistic mechanism has been shown for cell cycle arrest and apoptosis • PCR-array analysis has revealed the de-regulation of apoptosis and cell cycle genes • Maximum upregulation has been found for the Death-Associated Protein Kinase-2 gene • Data suggest that the mixture could be used as a clinical treatment.

Optofluidic ring resonator sensor for sensitive label-free detection of breast cancer antigen CA15-3 in human serum

Science.gov (United States)

Zhu, Hongying; Dale, Paul S.; Fan, Xudong

2009-05-01

Breast cancer is the most frequently diagnosed malignancy in women worldwide. Because of its great impact on society, a lot of research funding has been used to develop novel detection tools for aiding breast cancer diagnosis and prognosis. In this work, we demonstrated a simple, fast, and sensitive detection of circulating breast cancer biomarker CA15-3 with opto-fluidic ring resonator (OFRR) sensors. The OFRR sensor employs a thin-walled capillary with wall thickness less than 4 μm. The circular cross section of the capillary forms the optical ring resonator, in which the light circulates in the form of whispering gallery modes (WGMs). The capillary wall is thin enough that the evanescent field of the WGM extends into the capillary core and responds to refractive index changes in the capillary core or close to its interior surface. The WGM spectral position will change when the biomolecules bind to the surface, yielding quantitative and kinetic information about the biomolecule interaction. Here, the direct immunoassay method was employed for the detection of CA15-3 antigen without any signal amplification steps. The sensor performance in both PBS buffer and human serum were investigated, respectively. The experimental detection limit was 5 units/mL in PBS buffer and 30 units/mL for CA15-3 spiked in serum, both of which satisfied clinical diagnosis requirements. The potential use of the OFRR as the point-of-care device for breast cancer detection was tested by measuring the CA15-3 level in blood samples collected from stage IV breast cancer patients and the results were compared with standard clinical test.

Evaluation of a high-resolution, breast-specific, small-field-of-view gamma camera for the detection of breast cancer

International Nuclear Information System (INIS)

Brem, R.F.; Kieper, D.A.; Rapelyea, J.A.; Majewski, S.

2003-01-01

Purpose: The purpose of our study is to review the state of the art in nuclear medicine imaging of the breast (scintimammography) and to evaluate a novel, high-resolution, breast-specific gamma camera (HRBGC) for the detection of suspicious breast lesions. Materials and Methods: Fifty patients with 58 breast lesions in whom a scintimammogram was clinically indicated were prospectively evaluated with a general-purpose gamma camera and a HRBGC prototype. Nuclear studies were prospectively classified as negative (normal/benign) or positive (suspicious/malignant) by two radiologists, blinded to mammographic and histologic results with both the conventional and high-resolution. All lesions were confirmed by pathology. Results: Included in this study were 30 benign and 28 malignant lesions. The sensitivity for detection of breast cancer was 64.3% (18/28) with the conventional camera and 78.6% (22/28) with the HRBGC. Specificity of both systems was 93.3% (28/30). In the 18 nonpalpable cancers, sensitivity was 55.5% (10/18) and 72.2% (13/18) with the general-purpose camera and HRBGC, respectively. In cancers ≤ 1cm, 7 of 15 were detected with the general-purpose camera and 10 of 15 with the HRBGC. Four of the cancers (median size, 8.5 mm) detected with the HRBGC were missed by the conventional camera Conclusion: Evaluation of indeterminate breasts lesions with a high resolution, breast-specific gamma camera results in improved sensitivity for the detection of cancer with greater improvement demonstrated in nonpalpable and ≤1 cm cancers

Estimated risk for secondary cancer in the contra-lateral breast following radiation therapy of breast cancer

International Nuclear Information System (INIS)

Johansen, Safora; Danielsen, Turi; Olsen, Dag Rune

2008-01-01

Purpose. To facilitate a discussion about the impact of dose heterogeneity on the risk for secondary contralateral breast (CB) cancer predicted with linear and non linear models associated with primary breast irradiation. Methods and materials. Dose volume statistics of the CB calculated for eight patients using a collapsed cone algorithm were used to predict the excess relative risk (ERR) for cancer induction in CB. Both linear and non-linear models were employed. A sensitivity analysis demonstrating the impact of different parameter values on calculated ERR for the eight patients was also included in this study. Results. A proportionality assumption was established to make the calculations with a linear and non-linear model comparable. ERR of secondary cancer predicted by the linear model varied considerably between the patients, while the predicted ERR for the same patients using the non-linear model showed very small variation. The predicted ERRs by the two models were indistinguishable for small doses, i.e. below ∼3 Gy. The sensitivity analysis showed that the quadratic component of the radiation-induction pre-malignant cell term is negligible for lower dose level. The ERR is highly sensitive to the value of agr1 and agr2. Conclusions. Optimization of breast cancer radiation therapy, where also the risk for radiation induced secondary malignancies in the contralateral breast is taken into account, requires robust and valid risk assessment. The linear dose-risk model does not account for the complexity in the mechanisms underlying the development of secondary malignancies following exposure to radiation; this is particularly important when estimating risk associated with highly heterogeneous dose distributions as is the case in the contralateral breast of women receiving breast cancer irradiation

Retrospective and comparative analysis of 99mTc-Sestamibi breast specific gamma imaging versus mammography, ultrasound, and magnetic resonance imaging for the detection of breast cancer in Chinese women

International Nuclear Information System (INIS)

Yu, Xiuyan; Hu, Guoming; Zhang, Zhigang; Qiu, Fuming; Shao, Xuan; Wang, Xiaochen; Zhan, Hongwei; Chen, Yiding; Deng, Yongchuan; Huang, Jian

2016-01-01

Diagnosing breast cancer during the early stage may be helpful for decreasing cancer-related mortality. In Western developed countries, mammographies have been the gold standard for breast cancer detection. However, Chinese women usually have denser and smaller-sized breasts compared to Caucasian women, which decreases the diagnostic accuracy of mammography. However, breast specific gamma imaging, a type of molecular functional breast imaging, has been used for the accurate diagnosis of breast cancer and is not influenced by breast density. Our objective was to analyze the breast specific gamma imaging (BSGI) diagnostic value for Chinese women. During a 2-year period, 357 women were diagnosed and treated at our oncology department and received BSGI in addition to mammography (MMG), ultrasound (US) and magnetic resonance imaging (MRI) for diagnostic assessment. We investigated the sensitivity and specificity of each method of detection and compared the biological profiles of the four imaging methods. A total of 357 women received a final surgical pathology diagnosis, with 168 malignant diseases (58.5 %) and 119 benign diseases (41.5 %). Of these, 166 underwent the four imaging tests preoperatively. The sensitivity of BSGI was 80.35 and 82.14 % by US, 75.6 % by MMG, and 94.06 % by MRI. Furthermore, the breast cancer diagnosis specificity of BSGI was high (83.19 % vs. 77.31 % vs. 66.39 % vs. 67.69 %, respectively). The BSGI diagnostic sensitivity for mammographic breast density in women was superior to mammography and more sensitive for non-luminal A subtypes (luminal A vs. non-luminal A, 68.63 % vs. 88.30 %). BSGI may help improve the ability to diagnose early stage breast cancer for Chinese women, particularly for ductal carcinoma in situ (DCIS), mammographic breast density and non-luminal A breast cancer

Retrospective and comparative analysis of (99m)Tc-Sestamibi breast specific gamma imaging versus mammography, ultrasound, and magnetic resonance imaging for the detection of breast cancer in Chinese women.

Science.gov (United States)

Yu, Xiuyan; Hu, Guoming; Zhang, Zhigang; Qiu, Fuming; Shao, Xuan; Wang, Xiaochen; Zhan, Hongwei; Chen, Yiding; Deng, Yongchuan; Huang, Jian

2016-07-11

Diagnosing breast cancer during the early stage may be helpful for decreasing cancer-related mortality. In Western developed countries, mammographies have been the gold standard for breast cancer detection. However, Chinese women usually have denser and smaller-sized breasts compared to Caucasian women, which decreases the diagnostic accuracy of mammography. However, breast specific gamma imaging, a type of molecular functional breast imaging, has been used for the accurate diagnosis of breast cancer and is not influenced by breast density. Our objective was to analyze the breast specific gamma imaging (BSGI) diagnostic value for Chinese women. During a 2-year period, 357 women were diagnosed and treated at our oncology department and received BSGI in addition to mammography (MMG), ultrasound (US) and magnetic resonance imaging (MRI) for diagnostic assessment. We investigated the sensitivity and specificity of each method of detection and compared the biological profiles of the four imaging methods. A total of 357 women received a final surgical pathology diagnosis, with 168 malignant diseases (58.5 %) and 119 benign diseases (41.5 %). Of these, 166 underwent the four imaging tests preoperatively. The sensitivity of BSGI was 80.35 and 82.14 % by US, 75.6 % by MMG, and 94.06 % by MRI. Furthermore, the breast cancer diagnosis specificity of BSGI was high (83.19 % vs. 77.31 % vs. 66.39 % vs. 67.69 %, respectively). The BSGI diagnostic sensitivity for mammographic breast density in women was superior to mammography and more sensitive for non-luminal A subtypes (luminal A vs. non-luminal A, 68.63 % vs. 88.30 %). BSGI may help improve the ability to diagnose early stage breast cancer for Chinese women, particularly for ductal carcinoma in situ (DCIS), mammographic breast density and non-luminal A breast cancer.

Impact of contra-lateral breast reshaping on mammographic surveillance in women undergoing breast reconstruction following mastectomy for breast cancer.

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Nava, Maurizio B; Rocco, Nicola; Catanuto, Giuseppe; Falco, Giuseppe; Capalbo, Emanuela; Marano, Luigi; Bordoni, Daniele; Spano, Andrea; Scaperrotta, Gianfranco

2015-08-01

The ultimate goal of breast reconstruction is to achieve symmetry with the contra-lateral breast. Contra-lateral procedures with wide parenchymal rearrangements are suspected to impair mammographic surveillance. This study aims to evaluate the impact on mammographic detection of mastopexies and breast reductions for contralateral adjustment in breast reconstruction. We retrospectively evaluated 105 women affected by uni-lateral breast cancer who underwent mastectomy and immediate two-stage reconstruction between 2002 and 2007. We considered three groups according to the contra-lateral reshaping technique: mastopexy or breast reduction with inferior dermoglandular flap (group 1); mastopexy or breast reduction without inferior dermoglandular flap (group 2); no contra-lateral reshaping (group 3). We assessed qualitative mammographic variations and breast density in the three groups. Statistically significant differences have been found when comparing reshaped groups with non reshaped groups regarding parenchymal distortions, skin thickening and stromal edema, but these differences did not affect cancer surveillance. The surveillance mammography diagnostic accuracy in contra-lateral cancer detection was not significantly different between the three groups (p = 0.56), such as the need for MRI for equivocal findings at mammographic contra-lateral breast (p = 0.77) and the need for core-biopsies to confirm mammographic suspect of contra-lateral breast cancer (p = 0.90). This study confirms previous reports regarding the safety of mastopexies and breast reductions when performed in the setting of contra-lateral breast reshaping after breast reconstruction. Mammographic accuracy, sensitivity and specificity are not affected by the glandular re-arrangement. These results provide a further validation of the safety of current reconstructive paradigms. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dielectric and impedance spectroscopic studies of neodymium gallate

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Sakhya, Anup Pradhan, E-mail: npshakya31@gmail.com [Department of Physics, Bose Institute, 93/1 Acharya Prafulla Chandra Road, Kolkata 700009 (India); Dutta, Alo [Department of Condensed Matter Physics and Material Sciences, S. N. Bose National Centre for Basic Sciences, Block-JD, Sector-III, Salt Lake, Kolkata 700098 (India); Sinha, T.P. [Department of Physics, Bose Institute, 93/1 Acharya Prafulla Chandra Road, Kolkata 700009 (India)

2016-05-01

The AC electrical properties of a polycrystalline neodymium gallate, NdGaO{sub 3} (NGO), synthesized by the sol–gel method have been investigated by employing impedance spectroscopy in the frequency range from 42 Hz to 5 MHz and in the temperature range from 323 K to 593 K. The X-ray diffraction analysis shows that the compound crystallizes in the orthorhombic phase with Pbnm space group at room temperature. Two relaxation processes with different relaxation times are observed from the impedance as well as modulus spectroscopic measurements, which have been attributed to the grain and the grain boundary effects at different temperatures in NGO. The complex impedance data are analyzed by an electrical equivalent circuit consisting of a resistance and a constant phase element in parallel. It has been observed that the value of the capacitance and the resistance associated with the grain boundary is higher than those associated with the grain. The temperature dependent electrical conductivity shows the negative temperature coefficient of resistance. The frequency dependent conductivity spectra are found to follow the power law.

Potential benefit of (--epigallocatechin-3-gallate for macrovascular complications in diabetes

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L. Tang

2017-08-01

Full Text Available Vascular problems are the most common complications in diabetes. Substantial evidence from epidemiological and pathophysiological studies show that hyperglycemia is a major risk factor for macrovascular complications in patients with diabetes. (--Epigallocatechin-3-gallate (EGCG, the major catechin derived from green tea, is known to exert a variety of cardiovascular beneficial effects. The protective effects of EGCG in diabetes are also evident. However, whether EGCG is beneficial against macrovascular complications that occur in diabetes remains unknown. Our previous studies demonstrated that treatment of EGCG inhibits high glucose-induced vascular smooth muscle cell proliferation and suppresses high glucose-mediated vascular inflammation in human umbilical vein endothelial cells. Therefore, we hypothesize that EGCG might be an effective potential candidate to reduce the macrovascular complications in diabetes.

Utility of breast gammagraphy with technological 99mibi the diagnosis of breast disease

International Nuclear Information System (INIS)

Saure Sarria, Victor Manuel

2009-01-01

Breast cancer ranks first among causes of death in women around the world, in Cuba in 2003 the incidence was 20.3% with a mortality 15.6%. Among the complementary tests of this pathology has scan breast, in this work was to evaluate the usefulness of scintigraphy in breast cancer diagnosis, we performed an observational study where were included 66 patients admitted to hospital for cancer of Camaguey breast nodules suggestive of malignant neo proliferative process in the period from January 2004 to December 2006 were taken as a group study all women who attended the clinic at that time interval and meet the following conditions: Patients over 30 years informed consent of the study, breast tumors palpable at physical examination possibility of subsequent histological confirmation, some with questionable mammograms, dense breasts, stages I and II disease, the radiotracer was used as MIBI Tc-99, and the rectilinear scanner and computer computerized imager is A sensitivity of 95%, a specificity of 88% and predictive value 90.2% positive. Which it was concluded that breast scintigraphy is useful in diagnosis of the disease. (Author)

Molecular Imaging in Breast Cancer: From Whole-Body PET/CT to Dedicated Breast PET

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B. B. Koolen

2012-01-01

Full Text Available Positron emission tomography (PET, with or without integrated computed tomography (CT, using 18F-fluorodeoxyglucose (FDG is based on the principle of elevated glucose metabolism in malignant tumors, and its use in breast cancer patients is frequently being investigated. It has been shown useful for classification, staging, and response monitoring, both in primary and recurrent disease. However, because of the partial volume effect and limited resolution of most whole-body PET scanners, sensitivity for the visualization of small tumors is generally low. To improve the detection and quantification of primary breast tumors with FDG PET, several dedicated breast PET devices have been developed. In this nonsystematic review, we shortly summarize the value of whole-body PET/CT in breast cancer and provide an overview of currently available dedicated breast PETs.

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

International Nuclear Information System (INIS)

Mole, R.H.

1978-01-01

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

The presence of a membrane-bound progesterone receptor sensitizes the estradiol-induced effect on the proliferation of human breast cancer cells.

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Neubauer, Hans; Yang, Yang; Seeger, Harald; Fehm, Tanja; Cahill, Michael A; Tong, Xiaowen; Ruan, Xiangyan; Mueck, Alfred O

2011-08-01

Breast cancer risk is still an important topic regarding hormone therapy as well as oral contraception. Evidence that progestogens may play a crucial role is accumulating. Progesterone receptor membrane component 1 (PGRMC1) expressed in breast cancer may be important in tumorigenesis and thus may increase breast cancer risk. The aim of this project was to investigate the influence of different estradiol (E2) concentrations and the addition of two progestogens on MCF-7 breast cancer cells overexpressing PGRMC1. MCF-7 cells were stably transfected with PGRMC1 expression plasmid (MCF-7/PGRMC1-3HA [WT-12]). To test the effects of E2 and progestogens on cell proliferation, MCF-7 and WT-12 cells were stimulated with different concentrations of E2 (10 and 10 M) alone and in combination with progesterone and medroxyprogesterone acetate (each 10 M). E2 elicited a concentration-dependent proliferative effect on both cell lines, which was much more pronounced in WT-12 cells (50% vs 200%). This effect could be completely abrogated by the addition of the E2 antagonist fulvestrant. Addition of progesterone had no influence on the E2-induced effect, whereas medroxy-progesterone acetate enhanced the E2-induced effect at a low E2 concentration, which was, again, more pronounced in the WT-12 cells. The figures were between 20% and 40% in MCF-7 and between 60% and 250% in WT-12 cells. Overexpression of PGRMC1 sensitizes the proliferative response of the MCF-7 breast cancer cell line to estradiol. The effect of progestogens on breast cancer tumorigenesis may depend on the specific progestogen used for hormone therapy or oral contraception.

High resolution MRI of the breast at 3 T: which BI-RADS {sup registered} descriptors are most strongly associated with the diagnosis of breast cancer?

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Pinker-Domenig, K.; Helbich, T.H. [Medical University Vienna, Dept. of Radiology, Division of Molecular and Gender Imaging, Vienna (Austria); Bogner, W.; Gruber, S. [Medical University Vienna, Dept. of Radiology, MR Centre of Excellence, Vienna (Austria); Medical University Vienna, Dept. of Radiology, Vienna (Austria); Bickel, H. [Medical University Vienna, Dept. of Radiology, Division of Molecular and Gender Imaging, Vienna (Austria); Medical University Vienna, Dept. of Radiology, Vienna (Austria); Duffy, S. [Queen Mary University of London, Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry, London (United Kingdom); Schernthaner, M. [Medical University Vienna, Dept. of Radiology, Vienna (Austria); Dubsky, P. [Medical University Vienna, Dept. of Surgery, Vienna (Austria); Pluschnig, U. [Medical University Vienna, Dept. of Internal Medicine, Division of Oncology, Vienna (Austria); Rudas, M. [Medical University Vienna, Clinical Institute of Pathology, Vienna (Austria); Trattnig, S. [Medical University Vienna, Dept. of Radiology, MR Centre of Excellence, Vienna (Austria)

2012-02-15

To identify which breast lesion descriptors in the ACR BI-RADS registered MRI lexicon are most strongly associated with the diagnosis of breast cancer when performing breast MR imaging at 3 T. 150 patients underwent breast MR imaging at 3 T. Lesion size, morphology and enhancement kinetics were assessed according to the BI-RADS {sup registered} classification. Sensitivity, specificity and diagnostic accuracy were assessed. The effects of the BI-RADS {sup registered} descriptors on sensitivity and specificity were evaluated. Data were analysed using logistic regression. Histopathological diagnoses were used as the standard of reference. The sensitivity, specificity and diagnostic accuracy of breast MRI at 3 T was 99%, 81% and 93%, respectively. In univariate analysis, the final diagnosis of malignancy was positively associated with irregular shape (p < 0.001), irregular margin (p < 0.001), heterogeneous enhancement (p < 0.001), Type 3 enhancement kinetics (p = 0.02), increasing patient age (p = 0.02) and larger lesion size (p < 0.001). In multivariate analysis, significant associations with malignancy remained for mass shape (p = 0.06), mass margin (p < 0.001), internal enhancement pattern (p = 0.03) and Type 3 enhancement kinetics (p = 0.06). The ACR BI-RADS {sup registered} breast lesion descriptors that are mostly strongly associated with breast cancer in breast MR imaging at 3 T are lesion shape, lesion margin, internal enhancement pattern and Type 3 enhancement kinetics. (orig.)

Triple Test in Carcinoma Breast

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Sameer; Mukherjee, Arindam

2014-01-01

Introduction: The commonest clinical presentation in majority of breast pathology is a lump. A definite diagnosis of breast lump is very important for the surgeon to decide on the final course of treatment and also saves the patient from unnecessary physical, emotional and psychological trauma if there is a definite preoperative diagnosis of benign lesion. The present study was done to evaluate the effectiveness and relevance of “TRIPLE TEST”in diagnosis of carcinoma breast in rural labour class population. Materials and Methods: The present study was a prospective study conducted on patients over 35 years of age having palpable breast lumps presenting in the out patient department of general surgery, ESI Hospital Basaidarapur New Delhi, India. The duration of study was from May 2007 to June 2009 and a total of 100 cases were studied. Each patient was subjected to a detailed history, clinical breast examination ,diagnostic mammography and FNAC. In this study, the results of each modality was divided in three groups: benign, suspicious and malignant. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of each test was calculated individually and as combined. Result: Out of 100 patients enrolled in this study, 60 cases were benign and 40 cases were of malignant breast disease. The age of patients with carcinoma breast in the series varied from 35 years to 70 years. The highest incidence of malignancy noted was 30% in 41-50 years age group (4th decade) followed by 27.5% in 51-60 years age group (5th decade). The sensitivity of clinical examination was found to be 75%, specificity was 83.3%, positive predictive value (PPV) of 75% and diagnostic accuracy of 80%. The sensitivity, specificity, positive predictive value and diagnostic accuracy of mammography was calculated and was found to be 94.9% , 90% , 86% and 92% respectively. The sensitivity, specificity, positive predictive value and diagnostic accuracy of

Bone scanning in patients with breast carcinoma

International Nuclear Information System (INIS)

Inoue, Y.; Nishi, T.; Hirose, T.; Schichijo, Y.; Ibukuro, K.

1985-01-01

Skeletal imaging using radionuclides has proved to be a sensitive method for the detection of early bony metastases from breast carcinoma. Recent studies have found a relatively low rate of abnormal scans in patients with stage I and II breast cancers, and therefore it is open to question whether bone scanning should be part of the preoperative evaluation of any patient prior to breast surgery. We reviewed our experience with bone scans in 329 patients out of 406 histologically proven breast cancer patients to determine if any or all patients should have this procedure done routinely prior to breast surgery. (orig.) [de

COMPARISON OF CR MAMMOGRAPHY, SONOMAMMOGRAPHY AND REAL-TIME ELASTOGRAPHY IN EVALUATING BREAST LESIONS

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Onteddu Joji Reddy

2016-11-01

Full Text Available BACKGROUND Breast cancer is the most common cause of cancer deaths in women worldwide. As early detection can decrease the deaths due to breast cancer, high sensitive and specific tests are necessary to evaluate breast lesions. MATERIALS AND METHODS 80 patients with complaint of pain or lump in the breast or nipple discharge were evaluated by mammography, sonomammography and real-time elastography. Imaging studies were compared with the FNAC/biopsy of lesions. RESULTS Mammography has sensitivity, specificity, PPV, NPV as 80%, 95.5%, 93.3%, 86%, respectively. Sonomammography has sensitivity, specificity, PPV, NPV as 74.2%, 91%, 86%, 82%, respectively. Real-time elastography has sensitivity, specificity, PPV, NPV as 91.4%, 94.4%, 94.1%, 91.8%, respectively. Combined mammography and sonomammography has sensitivity, specificity, PPV, NPV as 82.8%, 93.3%, 90.6%, 87.5%, respectively. Combined sonomammography and elastography has sensitivity, specificity, PPV, NPV as 91.4%, 97.2%, 96.96%, 92.1%, respectively. CONCLUSIONS Combination of CR mammography, sonomammography and real-time elastography has high diagnostic sensitivity and specificity in the diagnosis of benign and malignant breast masses obviating the use of higher modalities like MRI, CAD and digital tomosynthesis, which is very useful in resource poor countries like India.

Postmortem validation of breast density using dual-energy mammography

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Molloi, Sabee; Ducote, Justin L.; Ding, Huanjun; Feig, Stephen A.

2014-01-01

Purpose: Mammographic density has been shown to be an indicator of breast cancer risk and also reduces the sensitivity of screening mammography. Currently, there is no accepted standard for measuring breast density. Dual energy mammography has been proposed as a technique for accurate measurement of breast density. The purpose of this study is to validate its accuracy in postmortem breasts and compare it with other existing techniques. Methods: Forty postmortem breasts were imaged using a dua...

Clinical applications of positron emission tomography in breast cancer patients

International Nuclear Information System (INIS)

Roemer, W.; Avril, N.; Schwaiger, M.

1997-01-01

Increased glucose metabolism by malignant tissue can be visualized with positron emission tomography (PET), using the radiolabeled glucose analogue F-18 fluorodeoxyglucose (FDG). Depending on the criteria of image interpretation FDG-PET allows detection of breast cancer with a sensitivity of 68% to 94 % and a specificity of 84 % to 97 %. However, sensitivity to visualize small tumors (< 1 cm) is limited. Positron emission tomography demonstrates tumor involvement of regional lymph nodes with high accuracy, predominantly in patients with advanced breast cancer. The sensitivity for the detection of axillary lymph node metastases was 79% with a corresponding specificity of 96 %. Lymph node metastases could not be identified in four of six patients with small primary breast cancer (stage pT1), resulting in a sensitivity of only 33% in these patients. By visualizing primary tumors and metastases in one imaging procedure, PET imaging may allow the effective staging of breast cancer patients. Further studies are needed to define the role of scintigraphic techniques for the diagnostic work-up in patients. (author)

Mammographic density and breast cancer risk in breast screening assessment cases and women with a family history of breast cancer.

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Duffy, Stephen W; Morrish, Oliver W E; Allgood, Prue C; Black, Richard; Gillan, Maureen G C; Willsher, Paula; Cooke, Julie; Duncan, Karen A; Michell, Michael J; Dobson, Hilary M; Maroni, Roberta; Lim, Yit Y; Purushothaman, Hema N; Suaris, Tamara; Astley, Susan M; Young, Kenneth C; Tucker, Lorraine; Gilbert, Fiona J

2018-01-01

Mammographic density has been shown to be a strong independent predictor of breast cancer and a causative factor in reducing the sensitivity of mammography. There remain questions as to the use of mammographic density information in the context of screening and risk management, and of the association with cancer in populations known to be at increased risk of breast cancer. To assess the association of breast density with presence of cancer by measuring mammographic density visually as a percentage, and with two automated volumetric methods, Quantra™ and VolparaDensity™. The TOMosynthesis with digital MammographY (TOMMY) study of digital breast tomosynthesis in the Breast Screening Programme of the National Health Service (NHS) of the United Kingdom (UK) included 6020 breast screening assessment cases (of whom 1158 had breast cancer) and 1040 screened women with a family history of breast cancer (of whom two had breast cancer). We assessed the association of each measure with breast cancer risk in these populations at enhanced risk, using logistic regression adjusted for age and total breast volume as a surrogate for body mass index (BMI). All density measures showed a positive association with presence of cancer and all declined with age. The strongest effect was seen with Volpara absolute density, with a significant 3% (95% CI 1-5%) increase in risk per 10 cm 3 of dense tissue. The effect of Volpara volumetric density on risk was stronger for large and grade 3 tumours. Automated absolute breast density is a predictor of breast cancer risk in populations at enhanced risk due to either positive mammographic findings or family history. In the screening context, density could be a trigger for more intensive imaging. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effect of the methyl gallate on the damage produced by radiation in leucocytes of peripheral blood of In vivo mouse

International Nuclear Information System (INIS)

Zarco M, A.

2007-01-01

The ionizing radiation produces a great variety of lesions in the deoxyribonucleic acid (DNA) through the formation of free radicals (RL), reason why the study about those made up with possible radioprotective property has been increased. The methyl gallate (MeG) it is an antioxidant derived of plants with capacity to capture RL. The objective of the present work was to determine the effect of the methyl gallate on the damage in the DNA taken place by gamma radiation in leukocytes of peripheral blood of in vivo mouse. The experimental design consisted of 4 groups of mice: It has a witness of the solvent group, dimethylsulfoxide (DMSO), in which was administer by intraperitoneal via 0.4 mL of a solution 1:8 of DMSO: H 2 O; a second group, denominated MeG witness, it was administered intraperitoneally with a dose of 0.1 μ moles/g of weight. Another group was used as radiation witness, reason why it was only treated with 1 Gray (Gy) of gamma radiation coming from a cobalt 60 source. At last, the group denominated problem it was administered with 0.1 μ moles of MeG/g of corporal weight 30 previous minutes to the irradiation with 1 Gy. In the comparison of the damage and repair curves obtained with the unicellular in gel electrophoresis technique among the irradiated groups, it was determined that there is one significant reduction of 15% in the DNA damage observed to the two minutes postradiation in the problem group with respect to the radiation witness. It was concluded that this decrease is due to the antioxidant effect of the methyl gallate and that therefore this compound has possibilities to act as radioprotector. (Author)

Oxygen-carbon nanotubes as a chemotherapy sensitizer for paclitaxel in breast cancer treatment.

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Yongkun Wang

Full Text Available To study the in vivo and in vitro effects of adding oxygen carbon nanotubes (CNTs to chemotherapy for breast cancer.MCF-7 and SK-BR-3 breast cancer cells were co-cultured with paclitaxel and then exposed to oxygen-CNTs under hypoxic conditions. Cell proliferation, viability, and apoptosis rate were analyzed. Hypoxia-inducible factor-1 alpha (HIF-1α expression was measured using reverse transcription-polymerase chain reaction (RT-PCR and western blot. Nude mice were used as a human breast cancer model to explore the impact of oxygen-CNTs on the in vivo chemotherapeutic effect of paclitaxel.Oxygen-CNTs had no significant effects on the growth of breast cancer cells under normoxia and hypoxia. However, in the hypoxic environment, oxygen-CNTs significantly enhanced the inhibitory effect of paclitaxel on cell proliferation, as well as the apoptosis rate. Under hypoxia, downregulation of HIF-1α and upregulation of caspase-3, caspase-8, caspase-9, LC3 and Beclin-1 were observed when paclitaxel was combined with oxygen-CNT. Furthermore, addition of oxygen-CNTs to chemotherapy was found to significantly reduce tumor weight in the tumor-bearing mice model.Oxygen-CNTs can significantly increase the chemotherapeutic effect of paclitaxel on breast cancer cells. Oxygen-CNTs may be a potential chemosensitizer in breast cancer therapy.

Newly Diagnosed Breast Cancer: Comparison of Contrast-enhanced Spectral Mammography and Breast MR Imaging in the Evaluation of Extent of Disease.

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Lee-Felker, Stephanie A; Tekchandani, Leena; Thomas, Mariam; Gupta, Esha; Andrews-Tang, Denise; Roth, Antoinette; Sayre, James; Rahbar, Guita

2017-11-01

Purpose To compare the diagnostic performances of contrast material-enhanced spectral mammography and breast magnetic resonance (MR) imaging in the detection of index and secondary cancers in women with newly diagnosed breast cancer by using histologic or imaging follow-up as the standard of reference. Materials and Methods This institutional review board-approved, HIPAA-compliant, retrospective study included 52 women who underwent breast MR imaging and contrast-enhanced spectral mammography for newly diagnosed unilateral breast cancer between March 2014 and October 2015. Of those 52 patients, 46 were referred for contrast-enhanced spectral mammography and targeted ultrasonography because they had additional suspicious lesions at MR imaging. In six of the 52 patients, breast cancer had been diagnosed at an outside institution. These patients were referred for contrast-enhanced spectral mammography and targeted US as part of diagnostic imaging. Images from contrast-enhanced spectral mammography were analyzed by two fellowship-trained breast imagers with 2.5 years of experience with contrast-enhanced spectral mammography. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated for both imaging modalities and compared by using the Bennett statistic. Results Fifty-two women with 120 breast lesions were included for analysis (mean age, 50 years; range, 29-73 years). Contrast-enhanced spectral mammography had similar sensitivity to MR imaging (94% [66 of 70 lesions] vs 99% [69 of 70 lesions]), a significantly higher PPV than MR imaging (93% [66 of 71 lesions] vs 60% [69 of 115 lesions]), and fewer false-positive findings than MR imaging (five vs 45) (P contrast-enhanced spectral mammography depicted 11 of the 11 secondary cancers (100%) and MR imaging depicted 10 (91%). Conclusion Contrast-enhanced spectral mammography is potentially as sensitive as MR imaging in the evaluation of extent of disease in newly diagnosed

Performance of computer-aided detection applied to full-field digital mammography in detection of breast cancers

International Nuclear Information System (INIS)

Sadaf, Arifa; Crystal, Pavel; Scaranelo, Anabel; Helbich, Thomas

2011-01-01

Objective: The aim of this retrospective study was to evaluate performance of computer-aided detection (CAD) with full-field digital mammography (FFDM) in detection of breast cancers. Materials and Methods: CAD was retrospectively applied to standard mammographic views of 127 cases with biopsy proven breast cancers detected with FFDM (Senographe 2000, GE Medical Systems). CAD sensitivity was assessed in total group of 127 cases and for subgroups based on breast density, mammographic lesion type, mammographic lesion size, histopathology and mode of presentation. Results: Overall CAD sensitivity was 91% (115 of 127 cases). There were no statistical differences (p > 0.1) in CAD detection of cancers in dense breasts 90% (53/59) versus non-dense breasts 91% (62/68). There was statistical difference (p 20 mm 97% (22/23). Conclusion: CAD applied to FFDM showed 100% sensitivity in identifying cancers manifesting as microcalcifications only and high sensitivity 86% (71/83) for other mammographic appearances of cancer. Sensitivity is influenced by lesion size. CAD in FFDM is an adjunct helping radiologist in early detection of breast cancers.

Radiation dose to contra lateral breast during treatment of breast malignancy by radiotherapy

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Chougule Arun

2007-01-01

Full Text Available Aims: External beam radiotherapy is being used regularly to treat the breast malignancy postoperatively. The contribution of collimator leakage and scatter radiation dose to contralateral breast is of concern because of high radio sensitivity of breast tissue for carcinogenesis. This becomes more important when the treated cancer breast patient is younger than 45 years and therefore the contralateral breast must be treated as organ at risk. Quantification of contralateral dose during primary breast irradiation is helpful to estimate the risk of radiation induced secondary breast malignancy. Materials and Methods: In present study contralateral breast dose was measured in 30 cancer breast patients undergoing external beam therapy by Co-60 teletherapy machine. Postoperative radiotherapy was delivered by medial and lateral tangential fields on alternate days in addition to supraclavicle field daily with 200 cGy/F to a total dose of 5000 cGy in 25 fractions. CaSO4: Dy themoluminescence dosimeter discs were employed for these measurements. Three TLD discs were put on the surface of skin of contra lateral breast, one at the level of nipple and two at 3 cms away from nipple on both side along the midline for each field. At the end treatment of each filed, TLD discs were removed and measured for dose after 24h on Thelmador - 6000 TLD reader. Results: The dose at the contra lateral breast nipple was to be 152.5 to 254.75 cGy for total primary breast dose of 5000 cGy in 25 equal fractions which amounted to 3.05-6.05% of total dose to diseased breast. Further it was observed that the maximum contribution of contralateral breast dose was due to medical tangential half blocked field. Conclusion: CaSO4; Dy thermoluminescence dosimetry is quite easy, accurate and convenient method to measure the contra lateral breast dose.

Symptom report in detecting breast cancer-related lymphedema

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Fu MR

2015-10-01

Full Text Available Mei R Fu,1 Deborah Axelrod,2,3 Charles M Cleland,1 Zeyuan Qiu,4 Amber A Guth,2,3 Robin Kleinman,2 Joan Scagliola,2 Judith Haber1 1College of Nursing, New York University, 2Department of Surgery, NYU School of Medicine, 3NYU Clinical Cancer Center, New York, NY, 4Department of Chemistry and Environmental Science, New Jersey Institute of Technology, Newark, NJ, USA Abstract: Breast cancer-related lymphedema is a syndrome of abnormal swelling coupled with multiple symptoms resulting from obstruction or disruption of the lymphatic system associated with cancer treatment. Research has demonstrated that with increased number of symptoms reported, breast cancer survivors' limb volume increased. Lymphedema symptoms in the affected limb may indicate a latent stage of lymphedema in which changes cannot be detected by objective measures. The latent stage of lymphedema may exist months or years before overt swelling occurs. Symptom report may play an important role in detecting lymphedema in clinical practice. The purposes of this study were to: 1 examine the validity, sensitivity, and specificity of symptoms for detecting breast cancer-related lymphedema and 2 determine the best clinical cutoff point for the count of symptoms that maximized the sum of sensitivity and specificity. Data were collected from 250 women, including healthy female adults, breast cancer survivors with lymphedema, and those at risk for lymphedema. Lymphedema symptoms were assessed using a reliable and valid instrument. Validity, sensitivity, and specificity were evaluated using logistic regression, analysis of variance, and areas under receiver operating characteristic curves. Count of lymphedema symptoms was able to differentiate healthy adults from breast cancer survivors with lymphedema and those at risk for lymphedema. A diagnostic cutoff of three symptoms discriminated breast cancer survivors with lymphedema from healthy women with a sensitivity of 94% and a specificity of 97

Prognosis method to predict small-sized breast cancer affected by fibrocystic disease

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S. A. Velichko

2017-01-01

Full Text Available The purpose of the study is to develop an effective radiological symptom-complex of small-sized breast cancer affected by fibrocystic breast disease by using multivariate statistical methods.Materials and methods. Radiological findings of small-sized breast cancer affected by fibrocystic mastopathy were analyzed in 100 patients with histologically verified diagnosis.Results. It was revealed that the conventional approach to the analysis of mammograms based on the detection of the primary, secondary and indirect mammographic signs of small-sized breast cancer is not effective enough - the sensitivity of mammography is only 62%. Fibrocystic disease and moderate-to-severe sclerosing adenosis make small-sized breast cancer hard to visualize by mammography. The detailed analysis of mammograms allowed us to identify the additional manifestations of small-sized breast cancer affected by mastopathy. The computer program allowing us to evaluate the risk of small-size breast cancer and the diagnostic algorithm for detecting small size breast cancer with sensitivity of 92% were developed. 

Antibacterial and antifungal activities of new acylated derivatives of epigallocatechin gallate

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Yoshimi eMatsumoto

2012-02-01

Full Text Available (--Epigallocatechin-3-O-gallate (EGCG has useful antiviral, antimicrobial, antitoxin, and antitumor properties. Previously, Mori, S. et al. (Bioorg Med Chem Lett 18:4249-4252, 2008 found that addition of long acyl chains (C16–18 to EGCG enhanced its anti-influenza virus activity up to 44-fold. The chemical stability of EGCG against oxidative degradation was also enhanced by acylation. We further evaluated the in vitro activity spectrum of the EGCG derivatives against a wide range of bacteria and fungi. A series of EGCG O-acyl derivatives were synthesized by lipase-catalyzed transesterification. These derivatives exhibited several-fold higher activities than EGCG, particularly against Gram-positive organisms. Antifungal activities of the derivatives were also 2 to 4-fold superior to those of EGCG. The activities of the EGCG derivatives against Gram-negative bacteria were not distinguishable from those of EGCG. Among the derivatives evaluated, MICs of dioctanoate, palmitate (C16, palmitoleate, and linolenate for 17 Staphylococcus aureus strains were 4–32 μg/ml, although MIC of EGCG for these 17 strains was >128 μg/ml. C16 demonstrated rapid bactericidal activity against MRSA at 25 μg/ml. The enhanced activity of C16 against S. aureus was supported by its increased membrane permeabilizing activity determined by increased SYTOX Green uptake. The EGCG derivatives were exported by the efflux pump AcrAB-TolC of Escherichia coli. The tolC deletion mutant exhibited higher sensitivity to C16 than to EGCG. Addition of long alkyl chains to EGCG significantly enhanced its activities against various bacteria and fungi, particularly against S. aureus including MRSA. C16 would be an alternative to antibiotics and disinfectants.

Usefulness of sonography in women less than 35 years old with palpable breast masses

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Kim, Hyun Ju; Chung, Hyun Ung; Park, Jin Gyoon; Seo, Jeong Jin; Kang, Heoung Keun; Kim, Jae Kyu; Chung, Hyon De [Chonnam National University College of Medicine, Gwangju (Korea, Republic of)

1994-12-15

To assess the usefulness of sonography in the evaluation of palpable mass in patients less than 35 years old,the breast sonograms and mammograms of 105 histopathologically proved cases were retrospectively reviewed. Breast parenchymal patterns on mammogram, sensitivity of sonography and mammography in the diagnosis of palpable breast masses, and sonographic findings of breast masses were analyzed. Grade IV breast parenchymal pattern was demonstrated in 44 of 76 mammogram (57.9%). The incidence of Grade IV pattern increased, as the patients' age became younger. The sensitivity of sonography (81.3%) was higher than that of mammography (45.3%) in the evaluation of the benign breast lesions. However, the sensitivity of both modalities were nearly equal (66.7% and 58.3% respectively) in the evaluation of the breast cancers. Sonographic findings of fibroadenoma included oval,well defined border, smooth contour, weak homogeneous internal echoes, posterior sonic enhancement, and bilateral shadows. On the other hand, breast cancer exhibited poorly defined border, irregular contour, and inhomogeneous hypoechoic mass with posterior sonic attenuation. In summary, sonography was useful in the evaluation of the palpable breast mass in women less than 35 years old. Choreoathetotic sonographic findings might help the differential diagnosis of breast masses

Usefulness of sonography in women less than 35 years old with palpable breast masses

Energy Technology Data Exchange (ETDEWEB)

Kim, Hyun Ju; Chung, Hyun Ung; Park, Jin Gyoon; Seo, Jeong Jin; Kang, Heoung Keun; Kim, Jae Kyu; Chung, Hyon De [Chonnam National University College of Medicine, Gwangju (Korea, Republic of)

1994-12-15

To assess the usefulness of sonography in the evaluation of palpable mass in patients less than 35 years old,the breast sonograms and mammograms of 105 histopathologically proved cases were retrospectively reviewed. Breast parenchymal patterns on mammogram, sensitivity of sonography and mammography in the diagnosis of palpable breast masses, and sonographic findings of breast masses were analyzed. Grade IV breast parenchymal pattern was demonstrated in 44 of 76 mammogram (57.9%). The incidence of Grade IV pattern increased, as the patients' age became younger. The sensitivity of sonography (81.3%) was higher than that of mammography (45.3%) in the evaluation of the benign breast lesions. However, the sensitivity of both modalities were nearly equal (66.7% and 58.3% respectively) in the evaluation of the breast cancers. Sonographic findings of fibroadenoma included oval,well defined border, smooth contour, weak homogeneous internal echoes, posterior sonic enhancement, and bilateral shadows. On the other hand, breast cancer exhibited poorly defined border, irregular contour, and inhomogeneous hypoechoic mass with posterior sonic attenuation. In summary, sonography was useful in the evaluation of the palpable breast mass in women less than 35 years old. Choreoathetotic sonographic findings might help the differential diagnosis of breast masses

Application of functional MRI in breast diseases

International Nuclear Information System (INIS)

Feng Yun; Liu Shiyuan; Wang Chenguang; Tao Xiaofeng; Wang Jinlin; Wang Jian

2007-01-01

Objective: To investigate the value of functional MRI in the diagnosis and differential diagnosis of breast diseases. Methods: Sixty-five patients with 68 lesions were enrolled in this study. Conventional T 1 WI and T 2 WI scan, dynamic contrast enhanced MRI, diffusion weighted imaging and 1 H single voxel MR spectroscopy were performed consequently. All lesions were verified by pathology, including 4 cases of breast adenosis, 22 fibroadenomas, 2 chronic inflammations, 3 cysts, 33 infitrating ductal carcinomas, 1 intraductal carcinoma and 3 cystosarcoma phyllodes tumors. Morphological features, maximum enhancement ratio, time-intensity curve, apparent diffusion coefficient and Choline peak were analyzed. Results: The detection rates of T 1 WI and T 2 WI were 14.7% (n=10) and 51.5% (n=35). The sensitivity, specificity, accuracy of dynamic contrast enhanced MRI for the malignant tumor were 94. 6%, 71.4% and 76.5% respectively. Retrospective study showed that diffusion weighted imaging, with the b value from 800 s/mm 2 to 1000 s/mm 2 , could be used to differentiate various types of breast lesions. 1 H signal voxel spectroscopy had a sensitivity of 51.4%, specificity of 82.6%, and accuracy of 67.6% for the malignent. The sensitivity, specificity and accuracy could reach 97.3%, 90.0% and 92.6% respectively by combining conventional scan, dynamic contrast enhanced MRI and MR spectroscopy. Conclusion: Functional MRI, with high sensitivity, specificity and accuracy, can be used widely in the diagnosis of malignant breast lesions. (authors)

Supplemental Screening for Breast Cancer in Women With Dense Breasts: A Systematic Review for the U.S. Preventive Services Task Force.

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Melnikow, Joy; Fenton, Joshua J; Whitlock, Evelyn P; Miglioretti, Diana L; Weyrich, Meghan S; Thompson, Jamie H; Shah, Kunal

2016-02-16

Screening mammography has lower sensitivity and specificity in women with dense breasts, who experience higher breast cancer risk. To perform a systematic review of reproducibility of Breast Imaging Reporting and Data System (BI-RADS) density categorization and test performance and clinical outcomes of supplemental screening with breast ultrasonography, magnetic resonance imaging (MRI), and digital breast tomosynthesis (DBT) in women with dense breasts and negative mammography results. MEDLINE, PubMed, EMBASE, and Cochrane database from January 2000 to July 2015. Studies reporting BI-RADS density reproducibility or supplemental screening results for women with dense breasts. Quality assessment and abstraction of 24 studies from 7 countries; 6 studies were good-quality. Three good-quality studies reported reproducibility of BI-RADS density; 13% to 19% of women were recategorized between "dense" and "nondense" at subsequent screening. Two good-quality studies reported that sensitivity of ultrasonography for women with negative mammography results ranged from 80% to 83%; specificity, from 86% to 94%; and positive predictive value (PPV), from 3% to 8%. The sensitivity of MRI ranged from 75% to 100%; specificity, from 78% to 94%; and PPV, from 3% to 33% (3 studies). Rates of additional cancer detection with ultrasonography were 4.4 per 1000 examinations (89% to 93% invasive); recall rates were 14%. Use of MRI detected 3.5 to 28.6 additional cancer cases per 1000 examinations (34% to 86% invasive); recall rates were 12% to 24%. Rates of cancer detection with DBT increased by 1.4 to 2.5 per 1000 examinations compared with mammography alone (3 studies). Recall rates ranged from 7% to 11%, compared with 7% to 17% with mammography alone. No studies examined breast cancer outcomes. Good-quality evidence was sparse. Studies were small and CIs were wide. Definitions of recall were absent or inconsistent. Density ratings may be recategorized on serial screening mammography

How I report breast magnetic resonance imaging studies for breast cancer staging and screening.

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Vinnicombe, Sarah

2016-07-25

Magnetic resonance imaging (MRI) of the breast is the most sensitive imaging technique for the diagnosis and local staging of primary breast cancer and yet, despite the fact that it has been in use for 20 years, there is little evidence that its widespread uncritical adoption has had a positive impact on patient-related outcomes.This has been attributed previously to the low specificity that might be expected with such a sensitive modality, but with modern techniques and protocols, the specificity and positive predictive value for malignancy can exceed that of breast ultrasound and mammography. A more likely explanation is that historically, clinicians have acted on MRI findings and altered surgical plans without prior histological confirmation. Furthermore, modern adjuvant therapy for breast cancer has improved so much that it has become a very tall order to show a an improvement in outcomes such as local recurrence rates.In order to obtain clinically useful information, it is necessary to understand the strengths and weaknesses of the technique and the physiological processes reflected in breast MRI. An appropriate indication for the scan, proper patient preparation and good scan technique, with rigorous quality assurance, are all essential prerequisites for a diagnostically relevant study.The use of recognised descriptors from a standardised lexicon is helpful, since assessment can then dictate subsequent recommendations for management, as in the American College of Radiology BI-RADS (Breast Imaging Reporting and Data System) lexicon (Morris et al., ACR BI-RADS® Atlas, Breast Imaging Reporting and Data System, 2013). It also enables audit of the service. However, perhaps the most critical factor in the generation of a meaningful report is for the reporting radiologist to have a thorough understanding of the clinical question and of the findings that will influence management. This has never been more important than at present, when we are in the throes of a

Influence of breast compression pressure on the performance of population-based mammography screening.

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Holland, Katharina; Sechopoulos, Ioannis; Mann, Ritse M; den Heeten, Gerard J; van Gils, Carla H; Karssemeijer, Nico

2017-11-28

In mammography, breast compression is applied to reduce the thickness of the breast. While it is widely accepted that firm breast compression is needed to ensure acceptable image quality, guidelines remain vague about how much compression should be applied during mammogram acquisition. A quantitative parameter indicating the desirable amount of compression is not available. Consequently, little is known about the relationship between the amount of breast compression and breast cancer detectability. The purpose of this study is to determine the effect of breast compression pressure in mammography on breast cancer screening outcomes. We used digital image analysis methods to determine breast volume, percent dense volume, and pressure from 132,776 examinations of 57,179 women participating in the Dutch population-based biennial breast cancer screening program. Pressure was estimated by dividing the compression force by the area of the contact surface between breast and compression paddle. The data was subdivided into quintiles of pressure and the number of screen-detected cancers, interval cancers, false positives, and true negatives were determined for each group. Generalized estimating equations were used to account for correlation between examinations of the same woman and for the effect of breast density and volume when estimating sensitivity, specificity, and other performance measures. Sensitivity was computed using interval cancers occurring between two screening rounds and using interval cancers within 12 months after screening. Pair-wise testing for significant differences was performed. Percent dense volume increased with increasing pressure, while breast volume decreased. Sensitivity in quintiles with increasing pressure was 82.0%, 77.1%, 79.8%, 71.1%, and 70.8%. Sensitivity based on interval cancers within 12 months was significantly lower in the highest pressure quintile compared to the third (84.3% vs 93.9%, p = 0.034). Specificity was lower in the

Silencing MED1 sensitizes breast cancer cells to pure anti-estrogen fulvestrant in vitro and in vivo.

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Lijiang Zhang

Full Text Available Pure anti-estrogen fulvestrant has been shown to be a promising ER antagonist for locally advanced and metastatic breast cancer. Unfortunately, a significant proportion of patients developed resistance to this type of endocrine therapy but the molecular mechanisms governing cellular responsiveness to this agent remain poorly understood. Here, we've reported that knockdown of estrogen receptor coactivator MED1 sensitized fulvestrant resistance breast cancer cells to fulvestrant treatment. We found that MED1 knockdown further promoted cell cycle arrest induced by fulvestrant. Using an orthotopic xenograft mouse model, we found that knockdown of MED1 significantly reduced tumor growth in mice. Importantly, knockdown of MED1 further potentiated tumor growth inhibition by fulvestrant. Mechanistic studies indicated that combination of fulvestrant treatment and MED1 knockdown is able to cooperatively inhibit the expression of ER target genes. Chromatin immunoprecipitation experiments further supported a role for MED1 in regulating the recruitment of RNA polymerase II and transcriptional corepressor HDAC1 on endogenous ER target gene promoter in the presence of fulvestrant. These results demonstrate a role for MED1 in mediating resistance to the pure anti-estrogen fulvestrant both in vitro and in vivo.

Management of breast lesions detectable only on MRI

International Nuclear Information System (INIS)

Siegmann-Luz, K.C.; Bahrs, S.D.; Preibsch, H.; Hattermann, V.; Claussen, C.D.

2014-01-01

Breast MR imaging has become established as the most sensitive imaging method for diagnosing breast cancer. As a result of the increasing examination volume and improved image quality, the number of breast lesions detected only on MRI and requiring further clarification has risen in recent years. According to the S3-guideline 'Diagnosis, Therapy, and Follow-Up of Breast Cancer' as revised in July 2012, institutions performing breast MRI should provide the option of an MRI-guided intervention for clarification. This review describes the indications, methods and results of MRI-guided interventions for the clarification of breast lesions only visible on MRI. Recent guidelines and study results are also addressed and alternative methods and pitfalls are presented. (orig.)

Enhancement of Cisplatin-Mediated Apoptosis in Ovarian Cancer Cells through Potentiating G2/M Arrest and p21 Upregulation by Combinatorial Epigallocatechin Gallate and Sulforaphane

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Huaping Chen

2013-01-01

Full Text Available Advanced-stage ovarian cancer is characterized by high mortality due to development of resistance to conventional chemotherapy. Novel compounds that can enhance the efficacy of conventional chemotherapy in ovarian cancer may overcome this drug resistance. Consumption of green tea (epigallocatechin gallate, EGCG and cruciferous vegetables (sulforaphane, SFN is inversely associated with occurrence of ovarian cancer and has anticancer effects through targeting multiple molecules in cancer cells. However, the effects of EGCG and SFN combinational treatment on ovarian cancer cells and on efficacy of cisplatin to these cells are unknown. In this study, EGCG or SFN was used to treat both cisplatin-sensitive (A2780 and cisplatin-resistant (A2780/CP20 ovarian cancer cells alone or in combination with cisplatin. We found that EGCG and SFN combinational treatment can reduce cell viability of both ovarian cancer cell lines time- and dose-dependently. Furthermore, EGCG and SFN combinational treatment can enhance cisplatin-induced apoptosis and G2/M phase arrest, thereby enhancing the efficacy of cisplatin on both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. EGCG and SFN combinational treatment upregulated p21 expression induced by cisplatin in cisplatin-sensitive ovarian cancer cells, while p27 expression was not regulated by these treatments. Collectively, these studies provide novel approaches to overcoming cisplatin chemotherapy resistance in ovarian cancer.

(-)-Epigallocatechin gallate inhibition of osteoclastic differentiation via NF-κB

International Nuclear Information System (INIS)

Lin, R.-W.; Chen, C.-H.; Wang, Y.-H.; Ho, M.-L.; Hung, S.-H.; Chen, I.-S.; Wang, G.-J.

2009-01-01

People who regularly drink tea have been found to have a higher bone mineral density (BMD) and to be at less risk of hip fractures than those who do not drink it. Green tea catechins such as (-)-epigallocatechin gallate (EGCG) have been reported to increase osteogenic functioning in mesenchymal stem cells. However, its effect on osteoclastogenesis remains unclear. In this study, we investigated the effect of EGCG on RANKL-activation osteoclastogenesis and NF-κB in RAW 264.7, a murine preosteoclast cell line. EGCG (10-100 μM) significantly suppressed the RANKL-induced differentiation of osteoclasts and the formation of pits in murine RAW 264.7 cells and bone marrow macrophages (BMMs). EGCG appeared to target osteoclastic differentiation at an early stage but had no cytotoxic effect on osteoclast precursors. In addition, it significantly inhibited RANKL-induced NF-κB transcriptional activity and nuclear translocation. We conclude that EGCG inhibits osteoclastogenesis through its activation of NF-κB.

Polarization study on doped lanthanum gallate electrolyte using impedance spectroscopy

Science.gov (United States)

Gong, Wenquan; Gopalan, Srikanth; Pal, Uday B.

2004-06-01

Alternating current complex impedance spectroscopy studies were conducted on symmetrical cells of the type [gas, electrode/La1-x Sr x Ga1-y Mg y O3 (LSGM) electrolyte/electrode, gas]. The electrode materials were slurry-coated on both sides of the LSGM electrolyte support. The electrodes selected for this investigation are candidate materials for solid oxide fuel cell (SOFC) electrodes. Cathode materials include La1-x Sr x MnO3 (LSM), La1-x Sr x Co y Fe1-y O3 (LSCF), a two-phase particulate composite consisting of LSM and doped-lanthanum gallate (LSGM), and LSCF + LSGM. Pt metal electrodes were also used for the purpose of comparison. Anode material investigated was the Ni + Ce0.85Gd0.15O2 composite. The study revealed important details pertaining to the charge-transfer reactions that occur in such electrodes. The information obtained can be used to design electrodes for intermediate temperature SOFCs based on LSGM electrolytes.

Detection of Methylated Circulating DNA as Noninvasive Biomarkers for Breast Cancer Diagnosis

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Cheuk, Isabella Wai Yin; Shin, Vivian Yvonne

2017-01-01

Internationally, breast cancer is the most common female cancer, and is induced by a combination of environmental, genetic, and epigenetic risk factors. Despite the advancement of imaging techniques, invasive sampling of breast epithelial cells is the only definitive diagnostic procedure for patients with breast cancer. To date, molecular biomarkers with high sensitivity and specificity for the screening and early detection of breast cancer are lacking. Recent evidence suggests that the detection of methylated circulating cell-free DNA in the peripheral blood of patients with cancer may be a promising quantitative and noninvasive method for cancer diagnosis. Methylation detection based on a multi-gene panel, rather than on the methylation status of a single gene, may be used to increase the sensitivity and specificity of breast cancer screening. In this review, the results of 14 relevant studies, investigating the efficacy of cell-free DNA methylation screening for breast cancer diagnosis, have been summarized. The genetic risk factors for breast cancer, the methods used for breast cancer detection, and the techniques and limitations related to the detection of cell-free DNA methylation status, have also been reviewed and discussed. From this review, we conclude that the analysis of peripheral blood or other samples to detect differentially methylated cell-free DNA is a promising technique for use in clinical settings, and may improve the sensitivity of screening for both, early detection and disease relapse, and thus improve the future prognosis of patients with breast cancer. PMID:28382090

Exploring the breast cancer patient journey: do breast cancer survivors need menopause management support?

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Tanna, Nuttan; Buijs, Helene; Pitkin, Joan

2011-12-01

Breast cancer survivors can be expected to suffer from menopause symptoms with estrogen deprivation due to cancer treatments, in addition to natural menopause-related estrogen loss. To gain an understanding of what support breast cancer patients have when they suffer from menopausal symptoms, and utilize findings to further inform National Health Service (NHS) care provision for breast cancer survivors. Qualitative study with focus group sessions targeting Caucasian and Asian women with breast cancer. Patient stories, with women describing their breast cancer journey and speaking about support received for any menopausal symptoms. Thematic data analysis of transcription. Breast cancer patients were not sure if they had menopausal symptoms or whether this was due to their breast cancer condition or treatment. Patients had an attitude of acceptance of menopausal symptoms and reported trying to cope with these by themselves. This research identifies a need for more information that is culturally sensitive on managing menopause symptoms, both as side-effects of breast cancer treatments as well as for affect on quality of life during the survivorship phase. Our work also gives insight into cultural remedies used for hot flushes by Asian patients, which they consider as 'cooling' foods. Breast cancer patients want to know whether side-effects of cancer treatment persist long term and how these can be managed. There is a need for improved patient support within any new NHS service models that are developed along breast cancer patient pathways, and inclusion of personalized advice for menopause symptoms.

Unenhanced breast MRI (STIR, T2-weighted TSE, DWIBS): An accurate and alternative strategy for detecting and differentiating breast lesions.

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Telegrafo, Michele; Rella, Leonarda; Stabile Ianora, Amato Antonio; Angelelli, Giuseppe; Moschetta, Marco

2015-10-01

To assess the role of STIR, T2-weighted TSE and DWIBS sequences for detecting and characterizing breast lesions and to compare unenhanced (UE)-MRI results with contrast-enhanced (CE)-MRI and histological findings, having the latter as the reference standard. Two hundred eighty consecutive patients (age range, 27-73 years; mean age±standard deviation (SD), 48.8±9.8years) underwent MR examination with a diagnostic protocol including STIR, T2-weighted TSE, THRIVE and DWIBS sequences. Two radiologists blinded to both dynamic sequences and histological findings evaluated in consensus STIR, T2-weighted TSE and DWIBS sequences and after two weeks CE-MRI images searching for breast lesions. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy for UE-MRI and CE-MRI were calculated. UE-MRI results were also compared with CE- MRI. UE-MRI sequences obtained sensitivity, specificity, diagnostic accuracy, PPV and NPV values of 94%, 79%, 86%, 79% and 94%, respectively. CE-MRI sequences obtained sensitivity, specificity, diagnostic accuracy, PPV and NPV values of 98%, 83%, 90%, 84% and 98%, respectively. No statistically significant difference between UE-MRI and CE-MRI was found. Breast UE-MRI could represent an accurate diagnostic tool and a valid alternative to CE-MRI for evaluating breast lesions. STIR and DWIBS sequences allow to detect breast lesions while T2-weighted TSE sequences and ADC values could be useful for lesion characterization. Copyright © 2015 Elsevier Inc. All rights reserved.

Utility of three-dimensional helical CT in the diagnosis of breast cancer

International Nuclear Information System (INIS)

Maeda, Yoshiaki; Hata, Yoshinobu; Matsuoka, Shinnichi; Nakajima, Nobuhisa; Ito, Toichi; Osada, Tadahiro; Sano, Fumio

2004-01-01

Although utility of three-dimensional (3D) helical CT for preoperative examination of breast cancer has been discussed, the accuracy of the helical CT in diagnosing breast cancer has not been fully evaluated. In this study 56 malignant and 28 benign breast tumors were evaluated preoperatively with 3D-helical CT, and their imaging results were compared with pathological findings of surgical specimens. Helical CT identified the presence of malignancy in 54 out of the 56 cancer cases tested and the sensitivity and specificity in distinguishing between malignant and benign tumors were 82% and 57%, respectively. The sensitivity and specificity in diagnosing the presence of metastatic axillary lymph nodes using helical CT were 70% and 80%, respectively. The sensitivity and specificity in diagnosing the presence of extensive intraductal component (EIC) using helical CT were 71% and 86%, respectively. Helical CT visualized all of the tumors in multifocal breast cancer cases. In conclusion, 3D-helical CT is a useful modality for preoperative examination of breast cancer, especially for assessing axillary lymph node status, and EIC, and will be helpful for conducting sentinel lymph node biopsy (SNLB) and breast-conserving surgery. (author)

Encapsulated nanoepigallocatechin-3-gallate and elemental selenium nanoparticles as paradigms for nanochemoprevention

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Wang D

2012-03-01

Full Text Available Dongxu Wang1, Ethan Will Taylor2, Yijun Wang1, Xiaochun Wan1, Jinsong Zhang11Key Laboratory of Tea Biochemistry and Biotechnology, School of Tea and Food Science, Anhui Agricultural University, Hefei, Anhui, People’s Republic of China; 2Department of Nanoscience, Joint School of Nanoscience and Nanoengineering, University of North Carolina at Greensboro, Greensboro, NC, USAAbstract: Chemoprevention that impedes one or more steps in carcinogenesis, via long-term administration of naturally occurring or synthetic compounds, is widely considered to be a crucial strategy for cancer control. Selenium (Se has chemopreventive effects, but its application is limited due to a low therapeutic index as shown in numerous animal experiments. In contrast to Se, which was known for its toxicity prior to the discovery of its beneficial effects, the natural compound epigallocatechin-3-gallate (EGCG was originally considered to be nontoxic. Due to its preventive effects on many types of cancer in various animal models, EGCG has been regarded as a prime example of a promising chemopreventive agent without major toxicity concerns. However, very recently, evidence has accumulated showing that efficacious doses of EGCG used in health promotion may not be far from its toxic dose level. Therefore, both Se and EGCG need to be modified by novel pharmaceutical technologies to attain enhanced efficacy and/or reduced toxicity. Nanotechnology may be one of these technologies. In support of this hypothesis, the characteristics of polylactic acid and polyethylene glycol-encapsulated nano-EGCG and elemental Se nanoparticles dispersed by bovine serum albumin are reviewed in this article. Encapsulation of EGCG to form nano-EGCG leads to its enhanced stability in plasma and remarkably superior chemopreventive effects, with more than tenfold dose advantages in inducing apoptosis and inhibition of both angiogenesis and tumor growth. Se at nanoparticle size (“Nano-Se”, compared

Body weight and sensitivity of screening mammography

DEFF Research Database (Denmark)

Njor, Sisse H.; von Euler-Chelpin, My; Tjønneland, Anne

2016-01-01

benefit more from screening than other women. Methods: We combined data from the Danish Diet, Cancer and Health study and the organised population-based screening mammography programme in Copenhagen, Denmark. Women were categorised according to body mass index (BMI) (...Aim: Obese women tend to participate less in breast cancer screening than normal weight women. However, obese women have fattier breast than normal weight women, and screening mammography works better in fatty than in dense breasts. One might, therefore, hypothesise that obese women would actually......, and 35+). We measured recall rate, sensitivity and specificity for subsequent screens with a 2-year follow-up period. Results: The study included 6787 women. The recall rate varied from 1.4% for women with BMI women with BMI 35+, test for trend p = 0.86. Sensitivity varied from 42% (95...

The Urtica dioica extract enhances sensitivity of paclitaxel drug to MDA-MB-468 breast cancer cells.

Science.gov (United States)

Mohammadi, Ali; Mansoori, Behzad; Aghapour, Mahyar; Shirjang, Solmaz; Nami, Sanam; Baradaran, Behzad

2016-10-01

Due to the chemo resistant nature of cancer cells and adverse effects of current therapies, researchers are looking for the most efficient therapeutic approach which has the lowest side effects and the highest toxicity on cancer cells. The aim of the present study was to investigate the synergic effect of Urtica dioica extract in combination with paclitaxel on cell death and invasion of human breast cancer MDA-MB-468 cell line. To determine the cytotoxic effects of Urtica dioica extract with paclitaxel, MTT assay was performed. The scratch test was exploited to assess the effects of Urtica dioica, Paclitaxel alone and combination on migration of cancer cells. The expression levels of snail-1, ZEB1, ZEB2, twist, Cdc2, cyclin B1 and Wee1 genes were quantified using qRT-PCR and western blot performed for snail-1expression. The effects of plant extract, Paclitaxel alone and combination on different phases of cell cycle was analyzed using flow cytometry. Results of MTT assay showed that Urtica dioica significantly destroyed cancer cells. Interestingly, Concurrent use of Urtica dioica extract with paclitaxel resulted in decreased IC50 dose of paclitaxel. Moreover, findings of scratch assay exhibited the inhibitory effects of Urtica dioica, Paclitaxel alone and combination on migration of MDA-MB-468 cell line. Our findings also demonstrated that the extract substantially decreased the Snail-1 and related gene expression. Ultimately, Cell cycle arrest occurred at G2/M phase post-treatment by deregulating Cdc2 and wee1. Our results demonstrated that the dichloromethane extract of Urtica dioica inhibit cell growth and migration. Also, Urtica dioica extract substantially increased sensitivity of breast cancer cells to paclitaxel. Therefore, it can be used as a potential candidate for treatment of breast cancer with paclitaxel. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

PAM50 breast cancer intrinsic subtypes and effect of gemcitabine in advanced breast cancer patients

DEFF Research Database (Denmark)

Jørgensen, Charlotte Levin Tykjær; Nielsen, Torsten O; Bjerre, Karsten D

2014-01-01

BACKGROUND: In vitro studies suggest basal breast cancers are more sensitive to gemcitabine relative to other intrinsic subtypes. The main objective of this study was to use specimens from a randomized clinical trial to evaluate whether the basal-like subtype identifies patients with advanced...... breast cancer who benefit from gemcitabine plus docetaxel (GD) compared to single agent docetaxel (D). MATERIAL AND METHODS: From patients randomly assigned to GD or D, RNA was isolated from archival formalin-fixed, paraffin-embedded primary breast tumor tissue and used for PAM50 intrinsic subtyping...... chemotherapy were analyzed by the Kaplan-Meier method, and Cox proportional hazards regression models. Data analysis was performed independently by the Danish Breast Cancer Cooperative Group (DBCG) statistical core and all statistical tests were two-sided. RESULTS: RNA from 270 patients was evaluable; 84...

Bilateral symmetry analysis of breast MRI

International Nuclear Information System (INIS)

Alterson, Robert; Plewes, Donald B

2003-01-01

Mammographic interpretation often uses symmetry between left and right breasts to indicate the site of potential tumour masses. This approach has not been applied to breast images obtained from MRI. We present an automatic technique for breast symmetry detection based on feature extraction techniques which does not require any efforts to co-register breast MRI data. The approach applies computer-vision techniques to detect natural biological symmetries in breast MR scans based on three objective measures of similarity: multiresolution non-orthogonal wavelet representation, three-dimensional intensity distributions and co-occurrence matrices. Statistical distributions that are invariant to feature localization are computed for each of the extracted image features. These distributions are later compared against each other to account for perceptual similarity. Studies based on 51 normal MRI scans of randomly selected patients showed that the sensitivity of symmetry detection rate approached 94%. The symmetry analysis procedure presented in this paper can be applied as an aid in detecting breast tissue changes arising from disease

99m-Tc tetrofosmin scintigraphy vs mammography in breast cancer detection

International Nuclear Information System (INIS)

Jaukovic, L.J.; Spaic, R.; Markovic, S.; Stankovic, N.; Dimitrijevic, S.; Strbac, M.

2002-01-01

99m-Tc tetrofosmin is a widely used radiotracer for breast cancer imaging. Routine mammography ,as a method for screening breast cancer patients, might be insufficient for diagnosis, especially in patients with dense breast. Aim: The aim of this study was to compare the results of mammography (MM) and scintimammography with 99m- Tc tetrofosmin (SMM) in detection of primary breast cancer. Method: Thirty patients with breast disease were included in study. All of them had clinical investigation, MM, SMM and surgical biopsy for final histological diagnosis. An amount of 600 MBq 99m- Tc tetrofosmin was injected intravenously in the arm opposite to the side of breast lesion. Ten minutes after injection planar breast 7-minutes scans were performed in supine (anterior) and prone (left and right lateral) position. Results: Out of 30 lesion breast cancer was histologically confirmed in 20 (15 ductal invasive, two lobular, one colloid, one papillar carcinoma and one case of cyst sarcoma phylodes- malignant type.) For MM sensitivity of 80%, specificity of 60% and accuracy of 76 % were obtained. At SMM 19/ 20 malignant lesions were detected. Only one false negative result was obtained in 1.0 cm lobular infiltrative cancer, although the smallest detectable lesion measured 0.6 cm. At pathohistology ten lesions presented benign. Four false positive results (two fibroadenomas, one lipogranuloma and one case of fibrocystic disease) were observed, six true negative results in four cases with fibrocystic disease and two fibroadenomas. The overall sensitivity of scintimammography was 95%, specificity 60% and accuracy 83%. Conclusion: We concluded that sensitivity of 99m-Tc tetrofosmin scintimammography in detection of breast cancer is superior to that of mammography. Our results suggest that 99m -Tc tetrofosmin is a suitable tumor seeking agent for breast cancer imaging

Intra-prosthetic breast MR virtual navigation: a preliminary study for a new evaluation of silicone breast implants.

Science.gov (United States)

Moschetta, Marco; Telegrafo, Michele; Capuano, Giulia; Rella, Leonarda; Scardapane, Arnaldo; Angelelli, Giuseppe; Stabile Ianora, Amato Antonio

2013-10-01

To assess the contribute of intra-prosthetic MRI virtual navigation for evaluating breast implants and detecting implant ruptures. Forty-five breast implants were evaluated by MR examination. Only patients with a clinical indication were assessed. A 1.5-T device equipped with a 4-channel breast coil was used by performing axial TSE-T2, axial silicone-only, axial silicone suppression and sagittal STIR images. The obtained dicom files were also analyzed by using virtual navigation software. Two blinded radiologists evaluated all MR and virtual images. Eight patients for a total of 13 implants underwent surgical replacement. Sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated for both imaging strategies. Intra-capsular rupture was diagnosed in 13 out of 45 (29%) implants by using MRI. Basing on virtual navigation, 9 (20%) cases of intra-capsular rupture were diagnosed. Sensitivity, specificity, accuracy, PPV and NPV values of 100%, 86%, 89%, 62% and 100%, respectively, were found for MRI. Virtual navigation increased the previous values up to 100%, 97%, 98%, 89% and 100%. Intra-prosthetic breast MR virtual navigation can represent an additional promising tool for the evaluation of breast implants being able to reduce false positives and to provide a more accurate detection of intra-capsular implant rupture signs. Copyright © 2013 Elsevier Inc. All rights reserved.

Sub-mSV breast XACT scanner: concept and design

Science.gov (United States)

Tang, Shanshan; Ren, Liqiang; Samant, Pratik; Chen, Jian; Liu, Hong; Xiang, Liangzhong

2016-04-01

Excessive exposure to radiation increases the risk of cancer. We present the concept and design of a new imaging paradigm, X-ray induced acoustic computed tomography (XACT). Applying this innovative technology to breast imaging, one single X-ray exposure can generate a 3D acoustic image, which dramatically reduces the radiation dose to patients when compared to beast CT. A theoretical model is developed to analyze the sensitivity of XACT. A noise equivalent pressure model is used for calculating the minimal radiation dose in XACT imaging. Furthermore, K-Wave simulation is employed to study the acoustic wave propagation in breast tissue. Theoretical analysis shows that the X-ray induced acoustic signal has a 100% relative sensitivity to the X-ray absorption (given that the percentage change in the X-ray absorption coefficient yields the same percentage change in the acoustic signal amplitude), but not to X-ray scattering. The final detection sensitivity is primarily limited by the thermal noise. The radiation dose can be reduced by a factor of 100 compared with the newly FDA approved breast CT. Reconstruction result shows that breast calcification with diameter of 80 μm can be observed in XACT image by using ultrasound transducers with 5.5 MHz center frequency. Therefore, with the proposed innovative technology, one can potentially reduce radiation dose to patient in breast imaging as compared with current x-ray modalities.

Breast density as indicator for the use of mammography or MRI to screen women with familial risk for breast cancer (FaMRIsc: a multicentre randomized controlled trial

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Saadatmand Sepideh

2012-10-01

Full Text Available Abstract Background To reduce mortality, women with a family history of breast cancer often start mammography screening at a younger age than the general population. Breast density is high in over 50% of women younger than 50 years. With high breast density, breast cancer incidence increases, but sensitivity of mammography decreases. Therefore, mammography might not be the optimal method for breast cancer screening in young women. Adding MRI increases sensitivity, but also the risk of false-positive results. The limitation of all previous MRI screening studies is that they do not contain a comparison group; all participants received both MRI and mammography. Therefore, we cannot empirically assess in which stage tumours would have been detected by either test. The aim of the Familial MRI Screening Study (FaMRIsc is to compare the efficacy of MRI screening to mammography for women with a familial risk. Furthermore, we will assess the influence of breast density. Methods/Design This Dutch multicentre, randomized controlled trial, with balanced randomisation (1:1 has a parallel grouped design. Women with a cumulative lifetime risk for breast cancer due to their family history of ≥20%, aged 30–55 years are eligible. Identified BRCA1/2 mutation carriers or women with 50% risk of carrying a mutation are excluded. Group 1 receives yearly mammography and clinical breast examination (n = 1000, and group 2 yearly MRI and clinical breast examination, and mammography biennially (n = 1000. Primary endpoints are the number and stage of the detected breast cancers in each arm. Secondary endpoints are the number of false-positive results in both screening arms. Furthermore, sensitivity and positive predictive value of both screening strategies will be assessed. Cost-effectiveness of both strategies will be assessed. Analyses will also be performed with mammographic density as stratification factor. Discussion Personalized breast cancer screening

Circulating microRNAs in breast cancer

DEFF Research Database (Denmark)

Hamam, Rimi; Hamam, Dana; Alsaleh, Khalid A.

2017-01-01

Effective management of breast cancer depends on early diagnosis and proper monitoring of patients' response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence...... in the past several years has highlighted the potential use of peripheral blood circulating nucleic acids such as DNA, mRNA and micro (mi)RNA in breast cancer diagnosis, prognosis and for monitoring response to anticancer therapy. Among these, circulating miRNA is increasingly recognized as a promising...... circulating miRNAs as diagnostic, prognostic or predictive biomarkers in breast cancer management....

Prevalence of breast tuberculosis: Retrospective analysis of 65 ...

African Journals Online (AJOL)

Prevalence of breast tuberculosis: Retrospective analysis of 65 patients attending a tertiary hospital in Durban, South Africa. ... Breast tuberculosis (BTB) is uncommon, but not rare. Knowledge of the ways in which it can ... Fine-needle aspiration cytology had sensitivity of only 28% compared with 94% for histology. Of those ...

Computer-aided detection system performance on current and previous digital mammograms in patients with contralateral metachronous breast cancer

International Nuclear Information System (INIS)

Kim, Seung Ja; Moon, Woo Kyung; Cho, Nariya; Chang, Jung Min

2012-01-01

Background: The computer-aided detection (CAD) system is widely used for screening mammography. The performance of the CAD system for contralateral breast cancer has not been reported for women with a history of breast cancer. Purpose: To retrospectively evaluate the performance of a CAD system on current and previous mammograms in patients with contralateral metachronous breast cancer. Material and Methods: During a 3-year period, 4945 postoperative patients had follow-up examinations, from whom we selected 55 women with contralateral breast cancers. Among them, 38 had visible malignant signs on the current mammograms. We analyzed the sensitivity and false-positive marks of the system on the current and previous mammograms according to lesion type and breast density. Results: The total visible lesion components on the current mammograms included 27 masses and 14 calcifications in 38 patients. The case-based sensitivity for all lesion types was 63.2% (24/38) with false-positive marks of 0.71 per patient. The lesion-based sensitivity for masses and calcifications was 59.3% (16/27) and 71.4% (10/14), respectively. The lesion-based sensitivity for masses in fatty and dense breasts was 68.8% (11/16) and 45.5% (5/11), respectively. The lesion-based sensitivity for calcifications in fatty and dense breasts was 100.0% (3/3) and 63.6% (7/11), respectively. The total visible lesion components on the previous mammograms included 13 masses and three calcifications in 16 patients, and the sensitivity for all lesion types was 31.3% (5/16) with false-positive marks of 0.81 per patient. On these mammograms, the sensitivity for masses and calcifications was 30.8% (4/13) and 33.3% (1/3), respectively. The sensitivity in fatty and dense breasts was 28.6% (2/7) and 33.3% (3/9), respectively. Conclusion: In the women with a history of breast cancer, the sensitivity of the CAD system in visible contralateral breast cancer was lower than in most previous reports using the same CAD

Overcoming resistance and restoring sensitivity to HER2-targeted therapies in breast cancer.

LENUS (Irish Health Repository)

Mohd Sharial, M S N

2012-12-01

Approximately 15%-23% of breast cancers overexpress human epidermal growth factor receptor 2 (HER2), which leads to the activation of signaling pathways that stimulate cell proliferation and survival. HER2-targeted therapy has substantially improved outcomes in patients with HER2-positive breast cancer. However, both de novo and acquired resistance are observed.

The sensitivity of pre-operative axillary staging in breast cancer: comparison of invasive lobular and ductal carcinoma.

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Topps, A; Clay, V; Absar, M; Howe, M; Lim, Y; Johnson, R; Bundred, N

2014-07-01

Axillary ultrasound (AUS) with fine-needle aspiration (FNA) biopsy of abnormal lymph nodes is important for pre-operative staging and planning the surgical management of the axilla. Invasive lobular carcinoma (ILC) metastases are thought to be difficult to detect because the cells are small and on cytology resemble lymphocytes. To investigate this we directly compared the sensitivity of pre-operative axillary staging between ILC and invasive ductal carcinoma (IDC). Consecutive patients that presented in a single breast unit with pure IDC between April 2005 and December 2006 and pure ILC between January 2008 and December 2012 were retrospectively identified from pathology records. Pre-operative axillary ultrasound and FNA biopsy results were compared with post-operative histopathology from the sentinel node biopsy (SNB) or axillary lymph node dissection (ALND). A total of 275 and 142 axillae were identified in the IDC and ILC groups respectively. In the node positive patients there was no significant difference in the sensitivity of AUS (IDC vs. ILC; 58.7% vs. 52.8%). However, there was a significant difference in the sensitivity of ultrasound-guided FNA biopsy of abnormal nodes (IDC vs. ILC; 98.4% vs. 53.6%; p < 0.001). AUS has comparative sensitivities between IDC and ILC populations. In contrast, FNA biopsy of abnormal axillary nodes is clearly less sensitive in the ILC group. In these patients, who have abnormal AUS, we suggest that a core biopsy is required to improve the pre-operative staging and prevent unnecessary surgical procedures. Copyright © 2014 Elsevier Ltd. All rights reserved.

Docetaxel modulates the delayed rectifier potassium current (IK) and ATP-sensitive potassium current (IKATP) in human breast cancer cells.

Science.gov (United States)

Sun, Tao; Song, Zhi-Guo; Jiang, Da-Qing; Nie, Hong-Guang; Han, Dong-Yun

2015-04-01

Ion channel expression and activity may be affected during tumor development and cancer growth. Activation of potassium (K(+)) channels in human breast cancer cells is reported to be involved in cell cycle progression. In this study, we investigated the effects of docetaxel on the delayed rectifier potassium current (I K) and the ATP-sensitive potassium current (I KATP) in two human breast cancer cell lines, MCF-7 and MDA-MB-435S, using the whole-cell patch-clamp technique. Our results show that docetaxel inhibited the I K and I KATP in both cell lines in a dose-dependent manner. Compared with the control at a potential of +60 mV, treatment with docetaxel at doses of 0.1, 1, 5, and 10 µM significantly decreased the I K in MCF-7 cells by 16.1 ± 3.5, 30.2 ± 5.2, 42.5 ± 4.3, and 46.4 ± 9% (n = 5, P < 0.05), respectively and also decreased the I KATP at +50 mV. Similar results were observed in MDA-MB-435S cells. The G-V curves showed no significant changes after treatment of either MCF-7 or MDA-MB-435S cells with 10 μM docetaxel. The datas indicate that the possible mechanisms of I K and I KATP inhibition by docetaxel may be responsible for its effect on the proliferation of human breast cancer cells.

The Ubiquitin-Conjugating Enzyme E2-EPF Is Overexpressed in Primary Breast Cancer and Modulates Sensitivity to Topoisomerase II Inhibition

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Donato Tedesco

2007-07-01

Full Text Available We identified the ubiquitin-conjugating enzyme E2EPF mRNA as differentially expressed in breast tumors relative to normal tissues and performed studies to elucidate its putative role in cancer. We demonstrated that overexpression of E2-EPF protein correlated with estrogen receptor (ER negativity in breast cancer specimens and that its expression is cell cycleregulated, suggesting a potential function for E2-EPF in cell cycle progression. However, reduction of E2EPF protein levels by > 80% using RNAi had no significant effects on the proliferation of HeLa cervical cancer cells or ER- MDA-MB-231 or MDA-MB-453 breast cancer cells. Because E2-EPF protein levels were elevated during the G2/M phase of the cell cycle and because E2-EPF mRNA in tumor specimens was frequently coexpressed with genes involved in cell cycle control, spindle assembly, and mitotic surveillance, the possibility that E2-EPF might have a function in the cellular response to agents that induce a G2 checkpoint or an M checkpoint was investigated. E2-EPF knockdown sensitized HeLa cells to the topoisomerase (topo II inhibitors etoposide and doxorubicin and also increased topo IIα protein levels. These data suggest that combined administration of topo II-directed drugs and E2-EPF inhibitors may enhance their clinical effectiveness.

The ubiquitin-conjugating enzyme E2-EPF is overexpressed in primary breast cancer and modulates sensitivity to topoisomerase II inhibition.

Science.gov (United States)

Tedesco, Donato; Zhang, Jianhuan; Trinh, Lan; Lalehzadeh, Guita; Meisner, Rene; Yamaguchi, Ken D; Ruderman, Daniel L; Dinter, Harald; Zajchowski, Deborah A

2007-07-01

We identified the ubiquitin-conjugating enzyme E2-EPF mRNA as differentially expressed in breast tumors relative to normal tissues and performed studies to elucidate its putative role in cancer. We demonstrated that overexpression of E2-EPF protein correlated with estrogen receptor (ER) negativity in breast cancer specimens and that its expression is cell cycle-regulated, suggesting a potential function for E2-EPF in cell cycle progression. However, reduction of E2-EPF protein levels by > 80% using RNAi had no significant effects on the proliferation of HeLa cervical cancer cells or ER(-) MDA-MB-231 or MDA-MB-453 breast cancer cells. Because E2-EPF protein levels were elevated during the G(2)/M phase of the cell cycle and because E2-EPF mRNA in tumor specimens was frequently coexpressed with genes involved in cell cycle control, spindle assembly, and mitotic surveillance, the possibility that E2-EPF might have a function in the cellular response to agents that induce a G(2) checkpoint or an M checkpoint was investigated. E2-EPF knockdown sensitized HeLa cells to the topoisomerase (topo) II inhibitors etoposide and doxorubicin and also increased topo IIalpha protein levels. These data suggest that combined administration of topo II-directed drugs and E2-EPF inhibitors may enhance their clinical effectiveness.

Proteome analysis of multidrug-resistant, breast cancer–derived microparticles

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Deep Pokharel

2014-08-01

Full Text Available Cancer multidrug resistance (MDR occurs when cancer cells evade the cytotoxic actions of chemotherapeutics through the active efflux of drugs from within the cells. Our group have previously demonstrated that multidrug-resistant breast cancer cells spontaneously shed microparticles (MPs and that these MPs can transfer resistance to drug-responsive cells and confer MDR on those cells in as little as 4 h. Furthermore, we also showed that, unlike MPs derived from leukaemia cells, breast cancer–derived MPs display a tissue selectivity in the transfer of P-glycoprotein (P-gp, transferring the resistance protein only to malignant breast cells. This study aims to define the proteome of breast cancer–derived MPs in order to understand the differences in protein profiles between those shed from drug-resistant versus drug-sensitive breast cancer cells. In doing so, we detail the protein cargo required for the intercellular transfer of MDR to drug-sensitive recipient cells and the factors governing the transfer selectivity to malignant breast cells. We describe the first proteomic analysis of MPs derived from human breast cancer cells using SDS PAGE and liquid chromatography–tandem mass spectrometry (LC/MS/MS, in which we identify 120 unique proteins found only in drug-resistant, breast cancer–derived MPs. Our results demonstrate that the MP-mediated transfer of P-gp to recipient cells occurs alongside CD44; the Ezrin, Radixin and Moesin protein family (ERM; and cytoskeleton motor proteins within the MP cargo.

Comparison between breast MRI and contrast-enhanced spectral mammography.

Science.gov (United States)

Łuczyńska, Elżbieta; Heinze-Paluchowska, Sylwia; Hendrick, Edward; Dyczek, Sonia; Ryś, Janusz; Herman, Krzysztof; Blecharz, Paweł; Jakubowicz, Jerzy

2015-05-12

The main goal of this study was to compare contrast-enhanced spectral mammography (CESM) and breast magnetic resonance imaging (MRI) with histopathological results and to compare the sensitivity, accuracy, and positive and negative predictive values for both imaging modalities. After ethics approval, CESM and MRI examinations were performed in 102 patients who had suspicious lesions described in conventional mammography. All visible lesions were evaluated independently by 2 experienced radiologists using BI-RADS classifications (scale 1-5). Dimensions of lesions measured with each modality were compared to postoperative histopathology results. There were 102 patients entered into CESM/MRI studies and 118 lesions were identified by the combination of CESM and breast MRI. Histopathology confirmed that 81 of 118 lesions were malignant and 37 were benign. Of the 81 malignant lesions, 72 were invasive cancers and 9 were in situ cancers. Sensitivity was 100% with CESM and 93% with breast MRI. Accuracy was 79% with CESM and 73% with breast MRI. ROC curve areas based on BI-RADS were 0.83 for CESM and 0.84 for breast MRI. Lesion size estimates on CESM and breast MRI were similar, both slightly larger than those from histopathology. Our results indicate that CESM has the potential to be a valuable diagnostic method that enables accurate detection of malignant breast lesions, has high negative predictive value, and a false-positive rate similar to that of breast MRI.

Screening and prevention of breast cancer in primary care.

Science.gov (United States)

Tice, Jeffrey A; Kerlikowske, Karla

2009-09-01

Mammography remains the mainstay of breast cancer screening. There is little controversy that mammography reduces the risk of dying from breast cancer by about 23% among women between the ages of 50 and 69 years, although the harms associated with false-positive results and overdiagnosis limit the net benefit of mammography. Women in their 70s may have a small benefit from screening mammography, but overdiagnosis increases in this age group as do competing causes of death. While new data support a 16% reduction in breast cancer mortality for 40- to 49-year-old women after 10 years of screening, the net benefit is less compelling in part because of the lower incidence of breast cancer in this age group and because mammography is less sensitive and specific in women younger than 50 years. Digital mammography is more sensitive than film mammography in young women with similar specificity, but no improvements in breast cancer outcomes have been demonstrated. Magnetic resonance imaging may benefit the highest risk women. Randomized trials suggest that self-breast examination does more harm than good. Primary prevention with currently approved medications will have a negligible effect on breast cancer incidence. Public health efforts aimed at increasing mammography screening rates, promoting regular exercise in all women, maintaining a healthy weight, limiting alcohol intake, and limiting postmenopausal hormone therapy may help to continue the recent trend of lower breast cancer incidence and mortality among American women.

Role of multidetector computed tomography in evaluating incidentally detected breast lesions.

Science.gov (United States)

Moschetta, Marco; Scardapane, Arnaldo; Lorusso, Valentina; Rella, Leonarda; Telegrafo, Michele; Serio, Gabriella; Angelelli, Giuseppe; Ianora, Amato Antonio Stabile

2015-01-01

Computed tomography (CT) does not represent the primary method for the evaluation of breast lesions; however, it can detect breast abnormalities, even when performed for other reasons related to thoracic structures. The aim of this study is to evaluate the potential benefits of 320-row multidetector CT (MDCT) in evaluating and differentiating incidentally detected breast lesions by using vessel probe and 3D analysis software with net enhancement value. Sixty-two breast lesions in 46 patients who underwent 320-row chest CT examination were retrospectively evaluated. CT scans were assessed searching for the presence, location, number, morphological features, and density of breast nodules. Net enhancement was calculated by subtracting precontrast density from the density obtained by postcontrast values. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of CT were calculated for morphological features and net enhancement. Thirty of 62 lesions were found to be malignant at histological examination and 32 were found to be benign. When morphological features were considered, the sensitivity, specificity, accuracy, PPV, and NPV of CT were 87%, 100%, 88%, 100%, and 50%, respectively. Based on net enhancement, CT reached a sensitivity, specificity, accuracy, PPV, and NPV of 100%, 94%, 97%, 94%, and 100%, respectively. MDCT allows to recognize and characterize breast lesions based on morphological features. Net enhancement can be proposed as an additional accurate feature of CT.

Examining the sensitivity of ultrasound-guided large core biopsy for invasive breast carcinoma in a population screening programme

International Nuclear Information System (INIS)

Rouse, Hannah C.; Ussher, Simon; Cawson, Jennifer N.; Kavanagh, Anne M.

2013-01-01

To evaluate the sensitivity of ultrasound-guided core-needle biopsy (UCB) in invasive breast carcinoma and to establish causes of false-negative biopsy in a population screening programme. We identified 571 consecutive women diagnosed with surgically proven invasive breast cancer. Histology from 14-gauge UCB was compared with surgical histology to identify true-positive and false-negative ultrasound core biopsies. True-positive and false-negative groups were compared for tumour size and histology. On blinded review of UCB images and pathology reports from false negative (n=20) and a random sample of true-positive cases (n=80), we compared core sample number and needle visualisation in the lesion. Of 571 carcinomas sampled with UCB, 551 (96.5%) were true positive and 20 (3.5%) were false negative. The mean core number was 2.0 (range 1–3) for false negatives and 2.25 (range 1–4) for true positives (P=0.27). Mean tumour sizes were 13.3 and 16.2mm for the false-negative and true-positive groups, respectively (P=0.25). Tubular carcinomas represented 30% (6/20) of false-negative cases compared with 5.1% (28/551) of the true-positive cases (P<0.001). On blinded review, needle visualisation within the lesion was demonstrated in 47.4% (9/19) of false-negative cases and 76.3% (61/80) of true-positive cases (P=0.02).We demonstrated a sensitivity of 96.5% with a mean of 2.21 cores. False-negative results were more likely in the absence of post-fire needle position verification and with tubular carcinomas. Neither tumour size nor core number predicted diagnostic accuracy.

MR imaging of the augmented and reconstructed breast

International Nuclear Information System (INIS)

Ivanov, V.; Kirova, G.

2013-01-01

Full text: Introduction: Various diagnostic methods are used to assess the changes in both the integrity of the implant, and the fibrous capsule of breast parenchyma. MRI has advantages over other diagnostic methods providing high tissue contrast, multi-faceted imaging and lack of ionizing radiation. What you will learn: MRI evaluation of breast augmentation approaches and their complications, MRI assessment of disease with malignant and benign characteristics in patients with breast implants, MRI assessment of breast reconstruction with autologous tissue. Discussion: Mammography after augmentation and reconstructive mammoplasty is hampered by the deformation of the breast parenchyma of the implant and the reduced compression. Postoperative scarring is also difficult to assess. MRI evaluation of implant rupture is accurate using the findings specific to it - linguine sign, teardrop sign or siliconomas. According to Gorczyca et al. MRI has a sensitivity 94% and specificity 97% in the evaluation of rupture. MRI mammography is highly sensitive - between 90 and 95%, in the detection of malignant, but it has limited specificity, which is its disadvantage. Malignant lesions can be represented as fibroadenomas, postoperative and inflammatory changes. Conclusion: Difficulties in the diagnosis of rupture of the implant, the primary and recurrent carcinoma based on clinical examination and inconclusive data from mammography and ultrasound imaging make MRI the method of choice in the evaluation of patients with breast implants

Epigallocatechin gallate incorporation into lignin enhances the alkaline delignification and enzymatic saccharification of cell walls

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Elumalai Sasikumar

2012-08-01

Full Text Available Abstract Background Lignin is an integral component of the plant cell wall matrix but impedes the conversion of biomass into biofuels. The plasticity of lignin biosynthesis should permit the inclusion of new compatible phenolic monomers such as flavonoids into cell wall lignins that are consequently less recalcitrant to biomass processing. In the present study, epigallocatechin gallate (EGCG was evaluated as a potential lignin bioengineering target for rendering biomass more amenable to processing for biofuel production. Results In vitro peroxidase-catalyzed polymerization experiments revealed that both gallate and pyrogallyl (B-ring moieties in EGCG underwent radical cross-coupling with monolignols mainly by β–O–4-type cross-coupling, producing benzodioxane units following rearomatization reactions. Biomimetic lignification of maize cell walls with a 3:1 molar ratio of monolignols and EGCG permitted extensive alkaline delignification of cell walls (72 to 92% that far exceeded that for lignified controls (44 to 62%. Alkali-insoluble residues from EGCG-lignified walls yielded up to 34% more glucose and total sugars following enzymatic saccharification than lignified controls. Conclusions It was found that EGCG readily copolymerized with monolignols to become integrally cross-coupled into cell wall lignins, where it greatly enhanced alkaline delignification and subsequent enzymatic saccharification. Improved delignification may be attributed to internal trapping of quinone-methide intermediates to prevent benzyl ether cross-linking of lignin to structural polysaccharides during lignification, and to the cleavage of ester intra-unit linkages within EGCG during pretreatment. Overall, our results suggest that apoplastic deposition of EGCG for incorporation into lignin would be a promising plant genetic engineering target for improving the delignification and saccharification of biomass crops.

Usefulness of breast MRI for diagnosing an extensive intraductal component of breast cancer: comparison with mammography and ultrasonography

International Nuclear Information System (INIS)

Kim, Tae Hee; Kang, Doo Kyung; Jung, Yong Sik; Yim, Hyun Ee

2006-01-01

An extensive intraductal component of breast cancer is a principal risk factor for local recurrence, and this is difficult to diagnose with performing only mammography. We investigated the usefulness of breast MRI for evaluating an extensive intraductal component of breast cancer, and we compared this modality with mammography and ultrasonography (US). From March 2003 to July 2004, 90 patients underwent breast MRI among all the patients who were suffering with breast cancer and for whom and EIC was ultimately revealed to be present or not. A total 83 patients with stage I and II breast cancer were finally included in this study. EIC positivity was defined according to the imaging data as follows: 1) microcalcifications beyond the tumor shadow or malignant microcalcifications without a tumor mass on mammography, 2) tubular hypoechoic structures adjacent to the tumor or architectural distortion with calcifications beyond the tumor on US, and 3) linear or ductal enhancement, segmental or regional clumped enhancement, and spotty nodular or reticular enhancement adjacent to the tumor on MRI. EIC was present in 41 patients and this finding was negative in 42 patients. The results were then compared those results from mammography and US. The sensitivities of detecting EIC by mammography, US and MRI were 48.6%, 67.5% and 80.5%, respectively, and the corresponding specificities were 92.3%, 73.2% and 69.0%, respectively. In the cases that were suspected to be EIC positive on more than two imaging modality, the positive predictive value (PPV) was 78.1%. In cases that were suspected of being EIC positive on just one imaging modality, the negative predictive value (NPV) was 75.0%. Breast MRI provides good information about an EIC of breast cancer and it is a more sensitive study than mammography and US, yet the specificity for the detection of EIC is highest on mammography. A combined evaluation by mammography, US and MRI is the most accurate way to diagnose an EIC of breast

How accurate is ultrasound in evaluating palpable breast masses ...

African Journals Online (AJOL)

Methods: Eighty palpable breast masses were evaluated at ultrasound and information about the characteristic features of the masses was recorded. An impression about the diagnosis was made and results were correlated with histology findings. Results: The overall sensitivity of ultrasound in detecting breast lumps was ...

1-ethyl gallate-2-substituted phenoxymethyl benzimidazoles: synthesis, molecular structure, antimicrobial activities and complex with cr(iii)

International Nuclear Information System (INIS)

Zhao, L.; Wu, J.; Wu, J.; Wang, Z.; Gu, H.

2017-01-01

The design of gallate and benzimidazole containing derivatives is expected to produce new bioactive molecules with multiple applications. Here the synthesis of eight novel benzimidazole compounds containing ethyl gallate and substituted phenoxymethyl units are reported. Firstly, the ring closure reaction between o-phenylendiamine and substituted phenoxyacetic acids resulted in 2-substituted phenoxymethyl benzimidazoles that were then modified by the N-hydroxyethylation with 2-chloroethyl alcohol under a phase transfer catalysis condition. The obtained 1-hydroxyethyl-2-substituted phenoxymethyl benzimidazoles were finally translated into the target title compounds 8a-h by an indirect esterification method in which three O-H groups of gallic acid were first protected by acetyls and deprotected after the esterification reaction by adding hydrazine hydrate. The structures of the title products 8a-h were fully characterized and confirmed by elemental analysis, MS, IR, 1H-NMR, 13C-NMR and single crystal X-ray diffraction techniques. Antimicrobial tests by inhibition zones indicated that these compounds exhibited diverse inhibitory effects against the test bacteria and fungi, and the type and position of the substituent groups in the phenoxymethyl moieties had obvious influence on their antimicrobial activities. Furthermore, the Cr(III) complex of 8h was synthesized, and various spectral, elemental and thermal analysis results confirmed that the central Cr(III) atom coordinated with adjacent hydroxyl groups of two 8h ligands, nitrate and H2O, respectively. (author)

Analysis of 30 breast implant rupture cases.

Science.gov (United States)

Tark, Kwan Chul; Jeong, Hii Sun; Roh, Tae Suk; Choi, Jong Woo

2005-01-01

Breast implants used for augmentation mammoplasty or breast reconstruction could rupture from various causes such as trauma or spontaneous failure. The objectives of this study were to investigate the relationships between the causes of implant rupture and the degree of capsular contracture, and then to evaluate the relative efficacies of specific signs on magnetic resonance imaging (MRI) known to be beneficial for diagnosing the rupture. A retrospective review identified patients with prosthetic implant rupture or impending rupture treated by the senior author. The 30 cases of implant rupture available for review were classified into two groups: intracapsular and extracapsular ruptures. The 30 cases of breast implant ruptures were analyzed with respect to the clinical symptoms and signs, the causes of rupture, the degree of capsular contracture, and therapeutic plans. Among the 30 cases, 14 patients who had undergone MRI during the diagnostic period were analyzed with respect to the relationships between MRI readings and operative findings. Spontaneous rupture of membranes was most common (80%), followed by failure because of trauma (7%) and valve or implant base (4%). The symptoms during implant rupture were contour deformity, palpated mass-like lesions, pain, and focal inflammation. According to the analysis of specific MRI signs, the sensitivity and specificity of the linguine sign were 87% and 100%, respectively, for intracapsular rupture. For extracapsular rupture, the sensitivity and specificity of the linguine sign were, respectively, 67% and 75%. The sensitivity and specificity of the rat-tail sign and tear drop sign were 14% and 50%, respectively. Breast implant rupture was correlated with the degree of capsular contracture in our study. Among the various specific MRI signs used in diagnosing the rupture, the linguine sign was reliable and had a high sensitivity and specificity, especially in cases of intracapsular rupture. On the other hand, the rat

Radiologists' Performance for Detecting Lesions and the Interobserver Variability of Automated Whole Breast Ultrasound

International Nuclear Information System (INIS)

Kim, Sung Hun; Kang, Bong Joo; Choi, Byung Gil; Choi, Jae Jung; Lee, Ji Hye; Song, Byung Joo; Choe, Byung Joo; Park, Sarah; Kim, Hyunbin

2013-01-01

To compare the detection performance of the automated whole breast ultrasound (AWUS) with that of the hand-held breast ultrasound (HHUS) and to evaluate the interobserver variability in the interpretation of the AWUS. AWUS was performed in 38 breast cancer patients. A total of 66 lesions were included: 38 breast cancers, 12 additional malignancies and 16 benign lesions. Three breast radiologists independently reviewed the AWUS data and analyzed the breast lesions according to the BI-RADS classification. The detection rate of malignancies was 98.0% for HHUS and 90.0%, 88.0% and 96.0% for the three readers of the AWUS. The sensitivity and the specificity were 98.0% and 62.5% in HHUS, 90.0% and 87.5% for reader 1, 88.0% and 81.3% for reader 2, and 96.0% and 93.8% for reader 3, in AWUS. There was no significant difference in the radiologists' detection performance, sensitivity and specificity (p > 0.05) between the two modalities. The interobserver agreement was fair to good for the ultrasonographic features, categorization, size, and the location of breast masses. AWUS is thought to be useful for detecting breast lesions. In comparison with HHUS, AWUS shows no significant difference in the detection rate, sensitivity and the specificity, with high degrees of interobserver agreement

Radiologists' Performance for Detecting Lesions and the Interobserver Variability of Automated Whole Breast Ultrasound

Energy Technology Data Exchange (ETDEWEB)

Kim, Sung Hun; Kang, Bong Joo; Choi, Byung Gil; Choi, Jae Jung; Lee, Ji Hye [Department of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Song, Byung Joo; Choe, Byung Joo [Department of General Surgery, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Park, Sarah [Department of Internal Medicine, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Kim, Hyunbin [CMC Clinical Research Coordinating Center, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of)

2013-07-01

To compare the detection performance of the automated whole breast ultrasound (AWUS) with that of the hand-held breast ultrasound (HHUS) and to evaluate the interobserver variability in the interpretation of the AWUS. AWUS was performed in 38 breast cancer patients. A total of 66 lesions were included: 38 breast cancers, 12 additional malignancies and 16 benign lesions. Three breast radiologists independently reviewed the AWUS data and analyzed the breast lesions according to the BI-RADS classification. The detection rate of malignancies was 98.0% for HHUS and 90.0%, 88.0% and 96.0% for the three readers of the AWUS. The sensitivity and the specificity were 98.0% and 62.5% in HHUS, 90.0% and 87.5% for reader 1, 88.0% and 81.3% for reader 2, and 96.0% and 93.8% for reader 3, in AWUS. There was no significant difference in the radiologists' detection performance, sensitivity and specificity (p > 0.05) between the two modalities. The interobserver agreement was fair to good for the ultrasonographic features, categorization, size, and the location of breast masses. AWUS is thought to be useful for detecting breast lesions. In comparison with HHUS, AWUS shows no significant difference in the detection rate, sensitivity and the specificity, with high degrees of interobserver agreement.

The Effect of California's Breast Density Notification Legislation on Breast Cancer Screening.

Science.gov (United States)

Chau, Stephanie Lynn; Alabaster, Amy; Luikart, Karin; Brenman, Leslie Manace; Habel, Laurel A

2017-04-01

Half of US states mandate women be notified if they have dense breasts on their mammogram, yet guidelines and data on supplemental screening modalities are limited. Breast density (BD) refers to the extent that breast tissue appears radiographically dense on mammograms. High BD reduces the sensitivity of screening mammography and increases breast cancer risk. The aim of this study was to determine the potential impact of California's 2013 BD notification legislation on breast cancer screening patterns. We conducted a cohort study of women aged 40 to 74 years who were members of a large Northern California integrated health plan (approximately 3.9 million members) in 2011-2015. We calculated pre- and post-legislation rates of screening mammography and magnetic resonance imaging (MRI). We also examined whether women with dense breasts (defined as BI-RADS density c or d) had higher MRI rates than women with nondense breasts (defined as BI-RADS density a or b). After adjustment for race/ethnicity, age, body mass index, medical facility, neighborhood median income, and cancer history, there was a relative 6.6% decrease (relative risk [RR] 0.934, confidence interval [CI] 0.92-0.95) in the rate of screening mammography, largely driven by a decrease among women screening MRI, with the greatest increase among the youngest women. In the postlegislation period, women with extremely dense breasts (BI-RADS d) had 2.77 times (CI 1.93-3.95) the odds of a MRI within 9 months of a screening mammogram compared with women with nondense breasts (BI-RADS b). In this setting, MRI rates increased in the postlegislation period. In addition, women with higher BD were more likely to have supplementary MRI. The decrease in mammography rates seen primarily among younger women may have been due to changes in national screening guidelines.

Environmental chemical exposures and breast cancer

Directory of Open Access Journals (Sweden)

E. Stanley

2016-02-01

Full Text Available As a hormone-sensitive condition with no single identifiable cause, breast cancer is a major health problem. It is characterized by a wide range of contributing factors and exposures occurring in different combinations and strengths across a lifetime that may be amplified during periods of enhanced developmental susceptibility and impacted by reproductive patterns and behaviours. The vast majority of cases are oestrogen-receptor positive and occur in women with no family history of the disease suggesting that modifiable risk factors are involved. A substantial body of evidence now links oestrogen-positive breast cancer with environmental exposures. Synthetic chemicals capable of oestrogen mimicry are characteristic of industrial development and have been individually and extensively assessed as risk factors for oestrogen-sensitive cancers. Existing breast cancer risk assessment tools do not take such factors into account. In the absence of consensus on causation and in order to better understand the problem of escalating incidence globally, an expanded, integrated approach broadening the inquiry into individual susceptibility breast cancer is proposed. Applying systems thinking to existing data on oestrogen-modulating environmental exposures and other oestrogenic factors characteristic of Westernisation and their interactions in the exposure, encompassing social, behavioural, environmental, hormonal and genetic factors, can assist in understanding cancer risks and the pursuit of prevention strategies. A new conceptual framework based on a broader understanding of the “system” that underlies the development of breast cancer over a period of many years, incorporating the factors known to contribute to breast cancer risk, could provide a new platform from which government and regulators can promulgate enhanced and more effective prevention strategies.

Abbreviated protocol for breast MRI: Are multiple sequences needed for cancer detection?

International Nuclear Information System (INIS)

Mango, Victoria L.; Morris, Elizabeth A.; David Dershaw, D.; Abramson, Andrea; Fry, Charles; Moskowitz, Chaya S.; Hughes, Mary; Kaplan, Jennifer; Jochelson, Maxine S.

2015-01-01

Highlights: • Abbreviated breast MR demonstrates high sensitivity for breast carcinoma detection. • Time to perform/interpret the abbreviated exam is shorter than a standard MRI exam. • An abbreviated breast MRI could reduce costs and make MRI screening more available. - Abstract: Objective: To evaluate the ability of an abbreviated breast magnetic resonance imaging (MRI) protocol, consisting of a precontrast T1 weighted (T1W) image and single early post-contrast T1W image, to detect breast carcinoma. Materials and methods: A HIPAA compliant Institutional Review Board approved review of 100 consecutive breast MRI examinations in patients with biopsy proven unicentric breast carcinoma. 79% were invasive carcinomas and 21% were ductal carcinoma in situ. Four experienced breast radiologists, blinded to carcinoma location, history and prior examinations, assessed the abbreviated protocol evaluating only the first post-contrast T1W image, post-processed subtracted first post-contrast and subtraction maximum intensity projection images. Detection and localization of tumor were compared to the standard full diagnostic examination consisting of 13 pre-contrast, post-contrast and post-processed sequences. Results: All 100 cancers were visualized on initial reading of the abbreviated protocol by at least one reader. The mean sensitivity for each sequence was 96% for the first post-contrast sequence, 96% for the first post-contrast subtraction sequence and 93% for the subtraction MIP sequence. Within each sequence, there was no significant difference between the sensitivities among the 4 readers (p = 0.471, p = 0.656, p = 0.139). Mean interpretation time was 44 s (range 11–167 s). The abbreviated imaging protocol could be performed in approximately 10–15 min, compared to 30–40 min for the standard protocol. Conclusion: An abbreviated breast MRI protocol allows detection of breast carcinoma. One pre and post-contrast T1W sequence may be adequate for detecting

Abbreviated protocol for breast MRI: Are multiple sequences needed for cancer detection?

Energy Technology Data Exchange (ETDEWEB)

Mango, Victoria L., E-mail: vlm2125@columbia.edu [Columbia University Medical Center, Herbert Irving Pavilion, 161 Fort Washington Avenue, 10th Floor, New York, NY 10032 (United States); Memorial Sloan-Kettering Cancer Center, Breast and Imaging Center, 300 East 66th Street, New York, NY 10065 (United States); Morris, Elizabeth A., E-mail: morrise@mskcc.org [Memorial Sloan-Kettering Cancer Center, Breast and Imaging Center, 300 East 66th Street, New York, NY 10065 (United States); David Dershaw, D., E-mail: dershawd@mskcc.org [Memorial Sloan-Kettering Cancer Center, Breast and Imaging Center, 300 East 66th Street, New York, NY 10065 (United States); Abramson, Andrea, E-mail: abramsoa@mskcc.org [Memorial Sloan-Kettering Cancer Center, Breast and Imaging Center, 300 East 66th Street, New York, NY 10065 (United States); Fry, Charles, E-mail: charles_fry@nymc.edu [Memorial Sloan-Kettering Cancer Center, Breast and Imaging Center, 300 East 66th Street, New York, NY 10065 (United States); New York Medical College, 40 Sunshine Cottage Rd, Valhalla, NY 10595 (United States); Moskowitz, Chaya S. [Memorial Sloan-Kettering Cancer Center, Breast and Imaging Center, 300 East 66th Street, New York, NY 10065 (United States); Hughes, Mary, E-mail: hughesm@mskcc.org [Memorial Sloan-Kettering Cancer Center, Breast and Imaging Center, 300 East 66th Street, New York, NY 10065 (United States); Kaplan, Jennifer, E-mail: kaplanj@mskcc.org [Memorial Sloan-Kettering Cancer Center, Breast and Imaging Center, 300 East 66th Street, New York, NY 10065 (United States); Jochelson, Maxine S., E-mail: jochelsm@mskcc.org [Memorial Sloan-Kettering Cancer Center, Breast and Imaging Center, 300 East 66th Street, New York, NY 10065 (United States)

2015-01-15

Highlights: • Abbreviated breast MR demonstrates high sensitivity for breast carcinoma detection. • Time to perform/interpret the abbreviated exam is shorter than a standard MRI exam. • An abbreviated breast MRI could reduce costs and make MRI screening more available. - Abstract: Objective: To evaluate the ability of an abbreviated breast magnetic resonance imaging (MRI) protocol, consisting of a precontrast T1 weighted (T1W) image and single early post-contrast T1W image, to detect breast carcinoma. Materials and methods: A HIPAA compliant Institutional Review Board approved review of 100 consecutive breast MRI examinations in patients with biopsy proven unicentric breast carcinoma. 79% were invasive carcinomas and 21% were ductal carcinoma in situ. Four experienced breast radiologists, blinded to carcinoma location, history and prior examinations, assessed the abbreviated protocol evaluating only the first post-contrast T1W image, post-processed subtracted first post-contrast and subtraction maximum intensity projection images. Detection and localization of tumor were compared to the standard full diagnostic examination consisting of 13 pre-contrast, post-contrast and post-processed sequences. Results: All 100 cancers were visualized on initial reading of the abbreviated protocol by at least one reader. The mean sensitivity for each sequence was 96% for the first post-contrast sequence, 96% for the first post-contrast subtraction sequence and 93% for the subtraction MIP sequence. Within each sequence, there was no significant difference between the sensitivities among the 4 readers (p = 0.471, p = 0.656, p = 0.139). Mean interpretation time was 44 s (range 11–167 s). The abbreviated imaging protocol could be performed in approximately 10–15 min, compared to 30–40 min for the standard protocol. Conclusion: An abbreviated breast MRI protocol allows detection of breast carcinoma. One pre and post-contrast T1W sequence may be adequate for detecting

Study of breast implant rupture: MRI versus surgical findings.

Science.gov (United States)

Vestito, A; Mangieri, F F; Ancona, A; Minervini, C; Perchinunno, V; Rinaldi, S

2012-09-01

This study evaluated the role of breast magnetic resonance (MR) imaging in the selective study breast implant integrity. We retrospectively analysed the signs of breast implant rupture observed at breast MR examinations of 157 implants and determined the sensitivity and specificity of the technique in diagnosing implant rupture by comparing MR data with findings at surgical explantation. The linguine and the salad-oil signs were statistically the most significant signs for diagnosing intracapsular rupture; the presence of siliconomas/seromas outside the capsule and/or in the axillary lymph nodes calls for immediate explantation. In agreement with previous reports, we found a close correlation between imaging signs and findings at explantation. Breast MR imaging can be considered the gold standard in the study of breast implants.

The utility of technetium - 99m Sestamibi scintimammography in breast cancer

International Nuclear Information System (INIS)

Howarth, D.M.; Sillar, R.; Clark, D.

1997-01-01

Full text: A large proportion of women with breast cancer are premenopausal, have dense breast tissue or have had previous breast surgery. The diagnostic accuracy of mammography for detecting breast cancer is reduced in this group of patients. The objective of this descriptive study was to assess the clinical utility of 99 mTc Sestamibi scintimammography in the diagnosis and management of patients with breast cancer. The study was a prospective analysis of 36 patients (38 lesions) with palpable breast lumps and three patients with impalpable breast masses detected on mammography or ultrasound. These patients were regarded as being diagnostically difficult by virtue of dense breast tissue, previous breast surgery or equivocal mammography. All patients had fine needle aspiration biopsies before scintimammography and excisional biopsy after scintimammography. The patients' ages ranged from 29 to 84 years (median 50 years). For palpable lesions the diagnostic sensitivity was 85 per cent, there were no false positives and overall diagnostic accuracy was 86 per cent compared to respective values for mammography of 50 per cent and 61 per cent. Two of the impalpable lesions were detected as true positives and one as a true negative. Metastatic disease was detected in the axillary lymph nodes with a 75 per cent sensitivity. Three patients had clinically and mammographically undetected multicentric disease detected on scintimammography which allowed appropriate modification of surgical excision. Breast cancer was detected in a patient with breast prostheses. These results indicate that scintimammography has an adjunctive role to mammography in further evaluating patients with breast cancer, particularly where the possibility of multi-focal lesions exists, thus allowing a one-stage surgical procedure to be performed and reducing the risk of local recurrence. In addition, scintimammography has a role in the diagnosis of breast cancer in patients with dense breast tissue and

Mucuna pruriens (L.) DC chemo sensitize human breast cancer cells via downregulation of prolactin-mediated JAK2/STAT5A signaling.

Science.gov (United States)

Sinha, Sonam; Sharma, Sonal; Vora, Jaykant; Shah, Heta; Srivastava, Anshu; Shrivastava, Neeta

2018-05-10

Mucuna pruriens (L.) DC (MP) is an ancient Indian medicinal plant traditionally used to treat Parkinson's disease. L-Dopa (LD), precursor of dopamine is abundantly found in the seeds of MP. L-dopa is a natural inhibitor of prolactin (PRL) hormone which is required to maintain lactation in women but it's over production (hyperprolactinemia) plays critical role in advancement of breast cancer. We aim to examine the pharmacological effect of LD and MP on this hyperprolactinemia associated breast cancer and related signaling for effective management of the disease. We also investigated chemo-sensitizing effect of MP on hyperprolactinemia-mediated cisplatin resistance. Methanolic seed extract of MP were prepared and analysed using HPLC. Effect of LD and MP on the cellular viability of breast cancer cells (T47D, MCF-7, MDA-MB-468 and MDA-MB-231) were evaluated using MTT assay. Further, effect of LD and MP on colony forming potential, DNA damage, cell cycle distribution and apoptosis was determined using agar/agarose method, comet assay and annexin and PI method followed by FACS analysis. To reveal the molecular mechanism involved in the anti-cancer activity of MP, transcriptional and translational level analysis of the key proteins involved in the PRL-mediated signaling, was performed using RT-PCR and western blot analysis. The effect of MP extract on PRL-mediated signaling was validated using dopaminergic agonist bromocriptine. MP extract and cisplatin was given in different combination with appropriate controls to check their effect on chemo-resistivity of breast cancer cells. Our results demonstrated that MP seed extract has the potential to inhibit cellular proliferation of PRL expressing T47D and MCF-7 breast cancer cells via induction of DNA damage, G1 phase of cell cycle arrest and apoptosis more effectively as compare to LD. Further, MP-mediated anti-cancerous effect was associated with the downregulation of PRL expression, further suppressing the JAK2/STAT5A

Contact sensitization to cosmetic series of allergens in a general population in Beijing.

Science.gov (United States)

Zhao, Jian; Li, Lin-Feng

2014-03-01

Cosmetic allergic contact dermatitis (CACD) due to common cosmetic allergens in standard series has been extensively studied; however, the prevalence of contact allergy to other cosmetic allergens other than those in standard series is largely unknown. In this study, the frequency of contact sensitization to a European cosmetic series of allergens (Chemotechnique Diagnostics, Vellinge, Sweden) in healthy university student volunteers were detected in Beijing. Of 201 students studied, fifty-eight exhibited positive results, and 9 of them reported had cosmetics related dermatitis previously. The total positivity rate was not correlated to gender. The leading allergens were thimerosal (19.4%), shellac (3.0%), cocamidopropyl betaine (2.0%), hexamethylenetetramine (1.5%), dodecyl gallate (1.5%), hexahydro-1,3,5-tris-(2-hydroxyethyl)triazine (1.0%) and methyldibromo glutaronitrile (1.0%). The positivity rate of thimerosal patch test in men (9.8%) was lower than that of women (23.6%, P cosmetic allergens in men and women (P > 0.05, Chi square test). These results suggested that some cosmetic-related contact allergies may be missed by just testing patients with the European standard series or T.R.U.E. test system only, we recommend shellac, cocamidopropyl betaine, hexamethylenetetramine and dodecyl gallate as the additionally candidates for patch testing in patients with suspected CACD. © 2014 Wiley Periodicals, Inc.

Understanding key performance indicators for breast support: An analysis of breast support effects on biomechanical, physiological and subjective measures during running.

Science.gov (United States)

Risius, Debbie; Milligan, Alexandra; Berns, Jason; Brown, Nicola; Scurr, Joanna

2017-05-01

To assess the effectiveness of breast support previous studies monitored breast kinematics and kinetics, subjective feedback, muscle activity (EMG), ground reaction forces (GRFs) and physiological measures in isolation. Comparing these variables within one study will establish the key performance variables that distinguish between breast supports during activities such as running. This study investigates the effects of changes in breast support on biomechanical, physiological and subjective measures during running. Ten females (34D) ran for 10 min in high and low breast supports, and for 2 min bare breasted (2.8 m·s -1 ). Breast and body kinematics, EMG, expired air and heart rate were recorded. GRFs were recorded during 10 m overground runs (2.8 m·s -1 ) and subjective feedback obtained after each condition. Of the 62 variables measured, 22 kinematic and subjective variables were influenced by changes in breast support. Willingness to exercise, time lag and superio-inferior breast velocity were most affected. GRFs, EMG and physiological variables were unaffected by breast support changes during running. Breast displacement reduction, although previously advocated, was not the most sensitive variable to breast support changes during running. Instead breast support products should be assessed using a battery of performance indicators, including the key kinematic and subjective variables identified here.

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

International Nuclear Information System (INIS)

Rodrigues-Peres, Raquel Mary; Cadore, Solange; Febraio, Stefanny; Heinrich, Juliana Karina; Serra, Katia Piton; Derchain, Sophie F M; Vassallo, Jose; Sarian, Luis Otavio

2013-01-01

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. 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. 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). 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 logical step is the assessment of whether the aluminum

Interference with Activator Protein-2 transcription factors leads to induction of apoptosis and an increase in chemo- and radiation- sensitivity in breast cancer cells

LENUS (Irish Health Repository)

Thewes, Verena

2010-05-11

Abstract Background Activator Protein-2 (AP-2) transcription factors are critically involved in a variety of fundamental cellular processes such as proliferation, differentiation and apoptosis and have also been implicated in carcinogenesis. Expression of the family members AP-2α and AP-2γ is particularly well documented in malignancies of the female breast. Despite increasing evaluation of single AP-2 isoforms in mammary tumors the functional role of concerted expression of multiple AP-2 isoforms in breast cancer remains to be elucidated. AP-2 proteins can form homo- or heterodimers, and there is growing evidence that the net effect whether a cell will proliferate, undergo apoptosis or differentiate is partly dependent on the balance between different AP-2 isoforms. Methods We simultaneously interfered with all AP-2 isoforms expressed in ErbB-2-positive murine N202.1A breast cancer cells by conditionally over-expressing a dominant-negative AP-2 mutant. Results We show that interference with AP-2 protein function lead to reduced cell number, induced apoptosis and increased chemo- and radiation-sensitivity. Analysis of global gene expression changes upon interference with AP-2 proteins identified 139 modulated genes (90 up-regulated, 49 down-regulated) compared with control cells. Gene Ontology (GO) investigations for these genes revealed Cell Death and Cell Adhesion and Migration as the main functional categories including 25 and 12 genes, respectively. By using information obtained from Ingenuity Pathway Analysis Systems we were able to present proven or potential connections between AP-2 regulated genes involved in cell death and response to chemo- and radiation therapy, (i.e. Ctgf, Nrp1, Tnfaip3, Gsta3) and AP-2 and other main apoptosis players and to create a unique network. Conclusions Expression of AP-2 transcription factors in breast cancer cells supports proliferation and contributes to chemo- and radiation-resistance of tumor cells by impairing the

Interference with Activator Protein-2 transcription factors leads to induction of apoptosis and an increase in chemo- and radiation-sensitivity in breast cancer cells

International Nuclear Information System (INIS)

Thewes, Verena; Orso, Francesca; Jäger, Richard; Eckert, Dawid; Schäfer, Sabine; Kirfel, Gregor; Garbe, Stephan; Taverna, Daniela; Schorle, Hubert

2010-01-01

Activator Protein-2 (AP-2) transcription factors are critically involved in a variety of fundamental cellular processes such as proliferation, differentiation and apoptosis and have also been implicated in carcinogenesis. Expression of the family members AP-2α and AP-2γ is particularly well documented in malignancies of the female breast. Despite increasing evaluation of single AP-2 isoforms in mammary tumors the functional role of concerted expression of multiple AP-2 isoforms in breast cancer remains to be elucidated. AP-2 proteins can form homo- or heterodimers, and there is growing evidence that the net effect whether a cell will proliferate, undergo apoptosis or differentiate is partly dependent on the balance between different AP-2 isoforms. We simultaneously interfered with all AP-2 isoforms expressed in ErbB-2-positive murine N202.1A breast cancer cells by conditionally over-expressing a dominant-negative AP-2 mutant. We show that interference with AP-2 protein function lead to reduced cell number, induced apoptosis and increased chemo- and radiation-sensitivity. Analysis of global gene expression changes upon interference with AP-2 proteins identified 139 modulated genes (90 up-regulated, 49 down-regulated) compared with control cells. Gene Ontology (GO) investigations for these genes revealed Cell Death and Cell Adhesion and Migration as the main functional categories including 25 and 12 genes, respectively. By using information obtained from Ingenuity Pathway Analysis Systems we were able to present proven or potential connections between AP-2 regulated genes involved in cell death and response to chemo- and radiation therapy, (i.e. Ctgf, Nrp1, Tnfaip3, Gsta3) and AP-2 and other main apoptosis players and to create a unique network. Expression of AP-2 transcription factors in breast cancer cells supports proliferation and contributes to chemo- and radiation-resistance of tumor cells by impairing the ability to induce apoptosis. Therefore, interference

Optimizing ultrasound detection for sensitive 3D photoacoustic breast tomography

NARCIS (Netherlands)

Xia, W.

2013-01-01

The standard modality for breast cancer detection is X-ray imaging. Diagnosis is performed after the triple assessment of X-ray mammography assisted by ultrasonog- raphy and biopsy. Magnetic resonance imaging (MRI) is sometimes used in specific problem solving such as contradictory results are

Positron emission mammography in breast cancer presurgical planning: comparisons with magnetic resonance imaging

International Nuclear Information System (INIS)

Schilling, Kathy; The, Juliette; Velasquez, Maria Victoria; Kahn, Simone; Saady, Matthew; Mahal, Ravinder; Chrystal, Larraine; Narayanan, Deepa; Kalinyak, Judith E.

2011-01-01

The objective of this study was to compare the performance characteristics of 18 F-fluorodeoxyglucose (FDG) positron emission mammography (PEM) with breast magnetic resonance imaging (MRI) as a presurgical imaging and planning option for index and ipsilateral lesions in patients with newly diagnosed, biopsy-proven breast cancer. Two hundred and eight women >25 years of age (median age = 59.7 ± 14.1 years) with biopsy-proven primary breast cancer enrolled in this prospective, single-site study. MRI, PEM, and whole-body positron emission tomography (WBPET) were conducted on each patient within 7 business days. PEM and WBPET images were acquired on the same day after intravenous administration of 370 MBq of FDG (median = 432.9 MBq). PEM and MRI images were blindly evaluated, compared with final surgical histopathology, and the sensitivity determined. Substudy analysis compared the sensitivity of PEM versus MRI in patients with different menopausal status, breast density, and use of hormone replacement therapy (HRT) as well as determination of performance characteristics for additional ipsilateral lesion detection. Two hundred and eight patients enrolled in the study of which 87% (182/208) were analyzable. Of these analyzable patients, 26.4% (48/182), 7.1% (13/182), and 64.2% (120/182) were pre-, peri-, and postmenopausal, respectively, and 48.4% (88/182) had extremely or heterogeneously dense breast tissue, while 33.5% (61/182) had a history of HRT use. Ninety-two percent (167/182) underwent core biopsy for index lesion diagnosis. Invasive cancer was found in 77.5% (141/182), while ductal carcinoma in situ (DCIS) and/or Paget's disease were found in 22.5% (41/182) of patients. Both PEM and MRI had index lesion depiction sensitivity of 92.8% and both were significantly better than WBPET (67.9%, p < 0.001, McNemar's test). For index lesions, PEM and MRI had equivalent sensitivity of various tumors, categorized by tumor stage as well as similar invasive tumor size

Correlation of the radioprotective effect of the methyl gallate on the ruptures induction in DNA and it effect in the capture of free radicals; Correlacion del efecto radioprotector del metil galato sobre la induccion de rupturas en el ADN y su efecto en la captura de radicales libres

Energy Technology Data Exchange (ETDEWEB)

Morales R, P.; Cabral P, A.; Cruz V, V.L.; Gonzalez B, F.; Zarco M, A. [ININ, 52750 La Marquesa, Estado de Mexico (Mexico)

2007-07-01

It is shown in alive, the capacity of the methyl gallate to reduce the induced ruptures in the DNA for {gamma} radiation. As well as to capture free radicals in a system in vitro. This suggests that the methyl gallate can be a radioprotector that acts capturing free radicals. (Author)

Exosomes decrease sensitivity of breast cancer cells to adriamycin by delivering microRNAs.

Science.gov (United States)

Mao, Ling; Li, Jian; Chen, Wei-Xian; Cai, Yan-Qin; Yu, Dan-Dan; Zhong, Shan-Liang; Zhao, Jian-Hua; Zhou, Jian-Wei; Tang, Jin-Hai

2016-04-01

While adriamycin (adr) offers improvement in survival for breast cancer (BCa) patients, unfortunately, drug resistance is almost inevitable. Mounting evidence suggests that exosomes act as a vehicle for genetic cargo and constantly shuttle biologically active molecules including microRNAs (miRNAs) between heterogeneous populations of tumor cells, engendering a resistance-promoting niche for cancer progression. Our recent study showed that exosomes from docetaxel-resistance BCa cells could modulate chemosensitivity by delivering miRNAs. Herein, we expand on our previous finding and explore the relevance of exosome-mediated miRNA delivery in resistance transmission of adr-resistant BCa sublines. We now demonstrated the selective packing of miRNAs within the exosomes (A/exo) derived from adr-resistant BCa cells. The highly expressed miRNAs in A/exo were significantly increased in recipient fluorescent sensitive cells (GFP-S) after A/exo incorporation. Gene ontology analysis of predicted targets showed that the top 30 most abundant miRNAs in A/exo were involved in crucial biological processes. Moreover, A/exo not only loaded miRNAs for its production and release but also carried miRNAs associated with Wnt signaling pathway. Furthermore, A/exo co-culture assays indicated that miRNA-containing A/exo was able to increase the overall resistance of GFP-S to adr exposure and regulate gene levels in GFP-S. Our results reinforce our earlier reports that adr-resistant BCa cells could manipulate a more deleterious microenvironment and transmit resistance capacity through altering gene expressions in sensitive cells by transferring specific miRNAs contained within exosomes.

Hormone resistance in two MCF-7 breast cancer cell lines is associated with reduced mTOR signaling, decreased glycolysis and increased sensitivity to cytotoxic drugs

Directory of Open Access Journals (Sweden)

Euphemia Yee Leung

2014-09-01

Full Text Available The mTOR pathway is a key regulator of multiple cellular signaling pathways and is a potential target for therapy. We have previously developed two hormone-resistant sub-lines of the MCF-7 human breast cancer line, designated TamC3 and TamR3, which were characterized by reduced mTOR signaling, reduced cell volume and resistance to mTOR inhibition. Here we show that these lines exhibit increased sensitivity to carboplatin, oxaliplatin, 5-fluorouracil, camptothecin, doxorubicin, paclitaxel, docetaxel and hydrogen peroxide. The mechanisms underlying these changes have not yet been characterized but may include a shift from glycolysis to mitochondrial respiration. If this phenotype is found in clinical hormone-resistant breast cancers, conventional cytotoxic therapy may be a preferred option for treatment.

Sensitivity and specificity of MR mammography with histopathological correlation in 250 breasts

Energy Technology Data Exchange (ETDEWEB)

Bone, B. [Dept. of Diagnostic Radiology, Univ. Hospital, Malmoe (Sweden); Aspelin, P. [Dept. of Diagnostic Radiology, Univ. Hospital, Malmoe (Sweden); Bronge, L. [Dept. of Diagnostic Radiology, Univ. Hospital, Malmoe (Sweden); Isberg, B. [Dept. of Diagnostic Radiology, Univ. Hospital, Malmoe (Sweden); Perbeck, L. [Dept. of Surgery, Karolinska Inst., Huddinge Hospital (Sweden); Veress, B. [Dept. of Pathology, Univ. Hospital, Malmoe (Sweden)

1996-03-01

The aim of our prospective study was to determine the diagnostic accuracy of MR mammography (MRM) in detecting malignant disease. In 231 consecutive patients scheduled for surgery because of mammographic or palpable lesions suspected of malignancy, the breasts were examined with T1-weighted transversal images using a 3-D fast low angle shot (FLASH) sequence. On pre- and 2 post-contrast images were obtained. Histological examination of the surgical specimens showed carcinoma in 155 breasts, of which 138 were invasive and 17 in situ. MRM detected 144 of the 155 malignancies and was false-negative in 11 cases. Eight of these MRM-missed tumours were invasive and 3 were in situ cancers. Benign lesions were found at microscopy in 95 breasts, of which MRM correctly diagnosed 69. The cellular composition of the 26 false-positive lesions (myxomatous stromal change, high vascularity, and epithelial or apocrine hyperplasia) might explain the false positivity. The sentitivity and specificity of MRM were 93% and 73%, respectively. MRM should be interpreted with caution, and supplemented with e.g. mammography and ultrasonography. (orig.).

The Ubiquitin-Conjugating Enzyme E2-EPF Is Overexpressed in Primary Breast Cancer and Modulates Sensitivity to Topoisomerase II Inhibition1

Science.gov (United States)

Tedesco, Donato; Zhang, Jianhuan; Trinh, Lan; Lalehzadeh, Guita; Meisner, Rene; Yamaguchi, Ken D; Ruderman, Daniel L; Dinter, Harald; Zajchowski, Deborah A

2007-01-01

We identified the ubiquitin-conjugating enzyme E2-EPF mRNA as differentially expressed in breast tumors relative to normal tissues and performed studies to elucidate its putative role in cancer. We demonstrated that overexpression of E2-EPF protein correlated with estrogen receptor (ER) negativity in breast cancer specimens and that its expression is cell cycle-regulated, suggesting a potential function for E2-EPF in cell cycle progression. However, reduction of E2-EPF protein levels by > 80% using RNAi had no significant effects on the proliferation of HeLa cervical cancer cells or ER- MDA-MB-231 or MDA-MB-453 breast cancer cells. Because E2-EPF protein levels were elevated during the G2/M phase of the cell cycle and because E2-EPF mRNA in tumor specimens was frequently coexpressed with genes involved in cell cycle control, spindle assembly, and mitotic surveillance, the possibility that E2-EPF might have a function in the cellular response to agents that induce a G2 checkpoint or an M checkpoint was investigated. E2-EPF knockdown sensitized HeLa cells to the topoisomerase (topo) II inhibitors etoposide and doxorubicin and also increased topo IIα protein levels. These data suggest that combined administration of topo II-directed drugs and E2-EPF inhibitors may enhance their clinical effectiveness. PMID:17710163

TIMP-1 overexpression does not affect sensitivity to HER2-targeting drugs in the HER2-gene-amplified SK-BR-3 human breast cancer cell line

DEFF Research Database (Denmark)

Deng, Xiaohong; Fogh, Louise; Lademann, Ulrik Axel

2013-01-01

affect sensitivity to the HER2-targeting drugs trastuzumab and lapatinib. SK-BR-3 human breast cancer cells were stably transfected with TIMP-1, characterized with regard to TIMP-1 protein expression, proliferation, and functionality of the secreted TIMP-1, and the sensitivity to trastuzumab...... and lapatinib was studied in five selected single-cell subclones expressing TIMP-1 protein at various levels plus the parental SK-BR-3 cell line. Both trastuzumab and lapatinib reduced cell viability, as determined by MTT assay, but the sensitivity to the drugs was not associated with the expression level...... to trastuzumab and lapatinib....

The influence of preoperative MRI of the breasts on recurrence rate in patients with breast cancer

International Nuclear Information System (INIS)

Fischer, Uwe; Baum, Friedemann; Heyden, Dorit von; Zachariae, Olivier; Liersch, Torsten; Funke, Matthias

2004-01-01

Preoperative MRI of the breasts has been proven to be the most sensitive imaging modality in the detection of multifocal or multicentric tumor manifestations as well as simultaneous contralateral breast cancer. The aim of the presented retrospective study was to evaluate the benefit of preoperative MRI for patients with breast cancer. Preoperative MRI performed in 121 patients (group A) were compared to 225 patients without preoperative MRI (group B). Patients of group A underwent contrast-enhanced MR imaging of the breast using a 2D FLASH sequence technique (TR/TE/FA 336 ms/5 ms/90diam.; 32 slices of 4-mm thickness, time of acquisition 1:27 min, contrast agent dosage 0.1 mmol Gd-DTPA/kg bw). All patients had histologically verified breast cancer and follow-up for more than 20 months (mean time group A: 40.3 months, group B: 41 months). Both groups received the same types of systemic treatment after breast conserving surgery. The in-breast tumor recurrence rate in group A was 1/86 (1.2%) compared to 9/133 (6.8%) in group B. Contralateral carcinoma were detected within follow-up in 2/121 (1.7%) in group A vs. 9/225 (4%) in group B. All results were statistically significant (P<0.001). Based on these results, preoperative MRI of the breasts is recommended in patients with histopathologically verified breast cancer for local staging

The influence of preoperative MRI of the breasts on recurrence rate in patients with breast cancer

Energy Technology Data Exchange (ETDEWEB)

Fischer, Uwe; Baum, Friedemann; Heyden, Dorit von [Diagnostisches Brustzentrum Goettingen, Womens Health Care Center Goettingen, Bahnhofsallee 1d, 37081 Goettingen (Germany); Zachariae, Olivier; Liersch, Torsten [Department of General Surgery, Georg-August-University of Goettingen, Robert-Koch-Strasse 40, 37075 Goettingen (Germany); Funke, Matthias [Department of Radiology, Georg-August-University of Goettingen, Robert-Koch-Strasse 40, 37075 Goettingen (Germany)

2004-10-01

Preoperative MRI of the breasts has been proven to be the most sensitive imaging modality in the detection of multifocal or multicentric tumor manifestations as well as simultaneous contralateral breast cancer. The aim of the presented retrospective study was to evaluate the benefit of preoperative MRI for patients with breast cancer. Preoperative MRI performed in 121 patients (group A) were compared to 225 patients without preoperative MRI (group B). Patients of group A underwent contrast-enhanced MR imaging of the breast using a 2D FLASH sequence technique (TR/TE/FA 336 ms/5 ms/90{sup o}; 32 slices of 4-mm thickness, time of acquisition 1:27 min, contrast agent dosage 0.1 mmol Gd-DTPA/kg bw). All patients had histologically verified breast cancer and follow-up for more than 20 months (mean time group A: 40.3 months, group B: 41 months). Both groups received the same types of systemic treatment after breast conserving surgery. The in-breast tumor recurrence rate in group A was 1/86 (1.2%) compared to 9/133 (6.8%) in group B. Contralateral carcinoma were detected within follow-up in 2/121 (1.7%) in group A vs. 9/225 (4%) in group B. All results were statistically significant (P<0.001). Based on these results, preoperative MRI of the breasts is recommended in patients with histopathologically verified breast cancer for local staging.

Efficacy of Mammographic Evaluation of Breast Cancer in Women Less Than 40 Years of Age: Experience from a Single Medical Center in Taiwan

Directory of Open Access Journals (Sweden)

Jane Wang

2007-09-01

Conclusion: Mammography has an acceptable sensitivity for the detection of breast cancer in women aged less than 40 years, regardless of different breast composition. Breast ultrasound can offer a higher sensitivity for such a population.

Multimodal breast cancer imaging using coregistered dynamic diffuse optical tomography and digital breast tomosynthesis

Science.gov (United States)

Zimmermann, Bernhard B.; Deng, Bin; Singh, Bhawana; Martino, Mark; Selb, Juliette; Fang, Qianqian; Sajjadi, Amir Y.; Cormier, Jayne; Moore, Richard H.; Kopans, Daniel B.; Boas, David A.; Saksena, Mansi A.; Carp, Stefan A.

2017-04-01

Diffuse optical tomography (DOT) is emerging as a noninvasive functional imaging method for breast cancer diagnosis and neoadjuvant chemotherapy monitoring. In particular, the multimodal approach of combining DOT with x-ray digital breast tomosynthesis (DBT) is especially synergistic as DBT prior information can be used to enhance the DOT reconstruction. DOT, in turn, provides a functional information overlay onto the mammographic images, increasing sensitivity and specificity to cancer pathology. We describe a dynamic DOT apparatus designed for tight integration with commercial DBT scanners and providing a fast (up to 1 Hz) image acquisition rate to enable tracking hemodynamic changes induced by the mammographic breast compression. The system integrates 96 continuous-wave and 24 frequency-domain source locations as well as 32 continuous wave and 20 frequency-domain detection locations into low-profile plastic plates that can easily mate to the DBT compression paddle and x-ray detector cover, respectively. We demonstrate system performance using static and dynamic tissue-like phantoms as well as in vivo images acquired from the pool of patients recalled for breast biopsies at the Massachusetts General Hospital Breast Imaging Division.

Lanthanum gallate and ceria composite as electrolyte for solid oxide fuel cells

International Nuclear Information System (INIS)

Li Shuai; Li Zhicheng; Bergman, Bill

2010-01-01

The composite of doped lanthanum gallate (La 0.9 Sr 0.1 Ga 0.8 Mg 0.2 O 2.85 , LSGM) and doped ceria (Ce 0.8 Sm 0.2 O 1.9 , CSO) was investigated as an electrolyte for solid oxide fuel cell (SOFC). The LSGM-CSO composite was examined by X-ray diffraction (XRD) and impedance spectroscopy. It was found that the sintered LSGM-CSO composite contains mainly fluorite CeO 2 phase and a minority impurity phase, Sm 3 Ga 5 O 12 . The LSGM-CSO composite electrolyte shows a small grain boundary response in the impedance spectroscopy as compared to LSGM and CSO pellets. The composite electrolyte exhibits the highest conductivity in the temperature range of 250-600 o C, compared to LSGM and CSO. The LSGM-CSO composite can be expected to be an attractive intermediate temperature electrolyte material for solid oxide fuel cells.

Methyl gallate from Acer barbinerve decreases melanin synthesis in Mel-Ab cells.

Science.gov (United States)

Kim, In Wook; jeong, Hyo-Soon; Kim, Jin Kyu; Lee, Jin-Koo; Kim, Hak Rim; Yun, Hye-Young; Baek, Kwang Jin; Kwon, Nyoun Soo; Park, Kyoung-Chan; Kim, Dong-Seok

2015-01-01

Methyl gallate (MG) was isolated from the bark of Acer barbinerve, which has traditionally been used in Oriental medicine. In the present study, we examined the effects of MG on melanin synthesis in Mel-Ab melanocyte cells. MG decreased melanin pigmentation in a concentration-dependent manner, but did not directly inhibit tyrosinase activity. Further analysis showed that MG had no effect on extracellular signal-regulated kinase (ERK) activation, but induced phosphorylation of glycogen synthase kinase (GSK)3β, which is known to increase β-catenin accumulation. Accordingly, the β-catenin level was increased by MG. However, a specific GSK3β inhibitor did not rescue the MG-induced inhibition of melanogenesis. Additionally, MG decreased the protein expression of microphthalmia-associated transcription factor (MITF) and tyrosinase, which regulate melanin synthesis. Based on these results, we conclude that MG inhibits melanogenesis by decreasing the expression of MITF and tyrosinase.

Association of symptoms and breast cancer in population-based mammography screening in Finland

Science.gov (United States)

Singh, Deependra; Malila, Nea; Pokhrel, Arun; Anttila, Ahti

2015-01-01

The study purpose was to assess association of symptoms at screening visits with detection of breast cancer among women aged 50–69 years during the period 2006–2010. Altogether 1.2 million screening visits were made and symptoms (lump, retraction, secretion etc.) were reported either by women or radiographer. Breast cancer risk was calculated for each symptom separately using logistic regression [odds ratio (OR)] and 95% confidence intervals (CIs). Of the 1,198,410 screening visits symptoms were reported in 298,220 (25%) visits. Breast cancer detection rate for women with and without symptoms was 7.8 per 1,000 and 4.7 per 1,000 screening visits, respectively, whereas lump detected 32 cancers per 1,000 screens. Women with lump or retraction had an increased risk of breast cancer, OR = 6.47, 95% CI 5.89−7.09 and OR = 2.19, 95% CI 1.92–2.49, respectively. The sensitivity of symptoms in detecting breast carcinoma was 35.5% overall. Individual symptoms sensitivity and specificity ranged from, 0.66 to 14.8% and 87.4 to 99.7%, respectively. Of 5,541 invasive breast cancers, 1,993 (36%) reported symptoms at screen. Breast cancer risk among women with lump or retraction was higher in large size tumors (OR = 9.20, 95% CI 8.08–10.5) with poorly differentiated grades (OR = 5.91, 95% CI 5.03–6.94) and regional lymph nodes involvement (OR = 6.47, 95% CI 5.67–7.38). This study was done in a setting where breast tumors size is generally small, and symptoms sensitivity and specificity in diagnosing breast tumors were limited. Importance of breast cancer symptoms in the cancer prevention and control strategy needs to be evaluated also in other settings. PMID:25160029

Design of a sensitive grating-based phase contrast mammography prototype (Conference Presentation)

Science.gov (United States)

Arboleda Clavijo, Carolina; Wang, Zhentian; Köhler, Thomas; van Stevendaal, Udo; Martens, Gerhard; Bartels, Matthias; Villanueva-Perez, Pablo; Roessl, Ewald; Stampanoni, Marco

2017-03-01

Grating-based phase contrast mammography can help facilitate breast cancer diagnosis, as several research works have demonstrated. To translate this technique to the clinics, it has to be adapted to cover a large field of view within a limited exposure time and with a clinically acceptable radiation dose. This indicates that a straightforward approach would be to install a grating interferometer (GI) into a commercial mammography device. We developed a wave propagation based optimization method to select the most convenient GI designs in terms of phase and dark-field sensitivities for the Philips Microdose Mammography (PMM) setup. The phase sensitivity was defined as the minimum detectable breast tissue electron density gradient, whereas the dark-field sensitivity was defined as its corresponding signal-to-noise Ratio (SNR). To be able to derive sample-dependent sensitivity metrics, a visibility reduction model for breast tissue was formulated, based on previous research works on the dark-field signal and utilizing available Ultra-Small-Angle X-ray Scattering (USAXS) data and the outcomes of measurements on formalin-fixed breast tissue specimens carried out in tube-based grating interferometers. The results of this optimization indicate the optimal scenarios for each metric are different and fundamentally depend on the noise behavior of the signals and the visibility reduction trend with respect to the system autocorrelation length. In addition, since the inter-grating distance is constrained by the space available between the breast support and the detector, the best way we have to improve sensitivity is to count on a small G2 pitch.

Impact of Breast Reader Assessment Strategy on mammographic radiologists' test reading performance.

Science.gov (United States)

Suleiman, Wasfi I; Rawashdeh, Mohammad A; Lewis, Sarah J; McEntee, Mark F; Lee, Warwick; Tapia, Kriscia; Brennan, Patrick C

2016-06-01

The detection of breast cancer is somewhat limited by human factors, and thus there is a need to improve reader performance. This study assesses whether radiologists who regularly undertake the education in the form of the Breast Reader Assessment Strategy (BREAST) demonstrate any changes in mammography interpretation performance over time. In 2011, 2012 and 2013, 14 radiologists independently assessed a year-specific BREAST mammographic test-set. Radiologists read a different single test-set once each year, with each comprising 60 digital mammogram cases. Radiologists marked the location of suspected lesions without computer-aided diagnosis (CAD) and assigned a confidence rating of 2 for benign and 3-5 for malignant lesions. The mean sensitivity, specificity, location sensitivity, JAFROC FOM and ROC AUC were calculated. A Kruskal-Wallis test was used to compare the readings for the 14 radiologists across the 3 years. Wilcoxon signed rank test was used to assess comparison between pairs of years. Relationships between changes in performance and radiologist characteristics were examined using a Spearman's test. Significant increases were noted in mean sensitivity (P = 0.01), specificity (P = 0.01), location sensitivity (P = 0.001) and JAFROC FOM (P = 0.001) between 2011 and 2012. Between 2012 and 2013, significant improvements were noted in mean sensitivity (P = 0.003), specificity (P = 0.002), location sensitivity (P = 0.02), JAFROC FOM (P = 0.005) and ROC AUC (P = 0.008). No statistically significant correlations were shown between the levels of improvement and radiologists' characteristics. Radiologists' who undertake the BREAST programme demonstrate significant improvements in test-set performance during a 3-year period, highlighting the value of ongoing education through the use of test-set. © 2016 The Royal Australian and New Zealand College of Radiologists.

Ultrasound -a useful complementary tool to mammography in assessment of symptomatic breast diseases

International Nuclear Information System (INIS)

Fatima, S.T.; Zahur, Z.; Jeilani, A.; Hussain, S.J.A.

2015-01-01

Breast cancer is the most common female malignancy worldwide. Pakistan has the highest incidence rate of breast cancer than any other Asian population. The purpose of the study was to evaluate the worth of sono-mammography in diagnosis of symptomatic breast diseases by comparing it with mammogram. Methods: In this cross-sectional validation study, 45 subjects with mean age of 45+-12.07 were included. Majority of the patients presented with complaint of breast lump. After complete history and clinical examination, all the patients had high resolution ultrasound of bilateral breasts and axilla followed by bilateral mammography. Histopathology was taken as gold standard in this study. The exclusion criteria were pregnancy and patients having direct clinical signs of breast malignancy. Results: Based on histopathology, out of 45 patients with breast symptoms, 12 patients had benign lesions, whereas 32 patients were diagnosed as the cases of breast cancers. Finally one patient did not have biopsy proven final diagnosis. Sensitivity and specificity of ultrasound were calculated to be 100% and 67% as compared to sensitivity and specificity of 90.6% and 91.7% for that of mammography. Conclusions: Ultrasound is a useful complementary tool to mammography in assessment of symptomatic breast diseases since it helps in characterization and localization of breast lesions seen on mammogram and it is not limited by dense breasts. Also it should be the considered as initial imaging technique for assessment of palpable breast lumps. (author)

An introduction to microwave imaging for breast cancer detection

CERN Document Server

Conceição, Raquel Cruz; O'Halloran, Martin

2016-01-01

This book collates past and current research on one of the most promising emerging modalities for breast cancer detection. Readers will discover how, as a standalone technology or in conjunction with another modality, microwave imaging has the potential to provide reliable, safe and comfortable breast exams at low cost. Current breast imaging modalities include X- ray, Ultrasound, Magnetic Resonance Imaging, and Positron Emission Tomography. Each of these methods suffers from limitations, including poor sensitivity or specificity, high cost, patient discomfort, and exposure to potentially harmful ionising radiation. Microwave breast imaging is based on a contrast in the dielectric properties of breast tissue that exists at microwave frequencies. The book begins by considering the anatomy and dielectric properties of the breast, contrasting historical and recent studies. Next, radar-based breast imaging algorithms are discussed, encompassing both early-stage artefact removal, and data independent and adaptive ...

Evaluation of Tc-99m Sestamibi Scintimammography in the diagnosis of breast cancer patients

International Nuclear Information System (INIS)

Santa Cruz, R.; Morales, R.; Cano, R.; Aguilar, C.; Lopez, D.; Carlos, I.; Vigil, C.; Velarde, R.; Cisneros, F.

2002-01-01

Aim: The purpose of this study was to evaluate the diagnostic accuracy of Tc-99m Sestamibi scintimammography in the diagnosis of breast cancer in patients with palpable breast lesions and to determine the sensitivity, specificity, and positive and negative predictive values of this method. Material and methods: Fifty women (mean ± SD 46±9y) referred for a suspicious breast lesion on physical examination and abnormal or indeterminate mammogram underwent Tc-99m sestamibi scintimammography. Lateral prone and supine images were obtained at 15 and 60 minutes after administration of 25 mCi of the tracer, in the contralateral arm to the breast lesion. Subsequently, excisional biopsy and/or fine needle aspiration biopsy were performed. Scintigraphic results were compared with biopsies. Results: Breast cancer of 3 different types was histologically confirmed in 44 patients. Benign lesions were found in 6 patients. Tc-99m Sestamibi scintimammography was positive in 42/44 breast cancer patients (sensitivity 95,5%) and was negative in 5/6 patients with benign lesions (specificity 83,3%). Positive predictive value was 97,7% and negative predictive value was 71,4%. Conclusion: Tc-99m Sestamibi scintimammography is a valuable complementary tool in the diagnosis of breast palpable lesions, with a high sensitivity and specificity. We suggest its use as an adjuvant technique in patients with doubtful mammographies

EPHB6 augments both development and drug sensitivity of triple-negative breast cancer tumours.

Science.gov (United States)

Toosi, Behzad M; El Zawily, Amr; Truitt, Luke; Shannon, Matthew; Allonby, Odette; Babu, Mohan; DeCoteau, John; Mousseau, Darrell; Ali, Mohsin; Freywald, Tanya; Gall, Amanda; Vizeacoumar, Frederick S; Kirzinger, Morgan W; Geyer, C Ronald; Anderson, Deborah H; Kim, TaeHyung; Welm, Alana L; Siegel, Peter; Vizeacoumar, Franco J; Kusalik, Anthony; Freywald, Andrew

2018-04-27

Triple-negative breast cancer (TNBC) tumours that lack expression of oestrogen, and progesterone receptors, and do not overexpress the HER2 receptor represent the most aggressive breast cancer subtype, which is characterised by the resistance to therapy in frequently relapsing tumours and a high rate of patient mortality. This is likely due to the resistance of slowly proliferating tumour-initiating cells (TICs), and understanding molecular mechanisms that control TICs behaviour is crucial for the development of effective therapeutic approaches. Here, we present our novel findings, indicating that an intrinsically catalytically inactive member of the Eph group of receptor tyrosine kinases, EPHB6, partially suppresses the epithelial-mesenchymal transition in TNBC cells, while also promoting expansion of TICs. Our work reveals that EPHB6 interacts with the GRB2 adapter protein and that its effect on enhancing cell proliferation is mediated by the activation of the RAS-ERK pathway, which allows it to elevate the expression of the TIC-related transcription factor, OCT4. Consistent with this, suppression of either ERK or OCT4 activities blocks EPHB6-induced pro-proliferative responses. In line with its ability to trigger propagation of TICs, EPHB6 accelerates tumour growth, potentiates tumour initiation and increases TIC populations in xenograft models of TNBC. Remarkably, EPHB6 also suppresses tumour drug resistance to DNA-damaging therapy, probably by forcing TICs into a more proliferative, drug-sensitive state. In agreement, patients with higher EPHB6 expression in their tumours have a better chance for recurrence-free survival. These observations describe an entirely new mechanism that governs TNBC and suggest that it may be beneficial to enhance EPHB6 action concurrent with applying a conventional DNA-damaging treatment, as it would decrease drug resistance and improve tumour elimination.

Laccase aided modification of nanofibrillated cellulose with dodecyl gallate

Directory of Open Access Journals (Sweden)

Päivi Saastamoinen

2012-11-01

Full Text Available Nanofibrillated cellulose, NFC, is an interesting wood fibre-based material that could be utilized in coatings, foams, composites, packages, dispersions, and emulsions, due to its high tensile strength and barrier properties, light weight, and stabilizing features. To improve applicability and properties of NFC, modification of its surface properties is often needed. In this study, the applicability of laccase-aided surface modification with hydrophobic dodecyl gallate (DOGA on unbleached NFC was investigated. Also, laccase-catalyzed polymerization of DOGA and other phenolic compounds with lignin moieties was investigated by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy (MALDI-TOF MS. NFC modified with T. hirsuta-based laccase and DOGA showed decreased hydrophilicity, as compared with the native NFC, when coated on a paper surface. When dried as free-standing films, the surface properties of chemo-enzymatically modified NFC resembled those of the native NFC. The effect of modification was thus greatly influenced by different surface formation in differently prepared samples. Also, changing of the dispersion properties of DOGA by enzymatic polymerization affected the surface properties of the dried NFC samples. Covalent bonding between DOGA and NFC was not the main factor affecting the surface properties of the NFC in free-standing films or coatings.

Dose Tc-99m MIBI scintimammography provide more information additive to contrast enhanced MRI in highly suspected breast cancer patients?

International Nuclear Information System (INIS)

Kim, Seong Jang; Kim, In Ju; Kim, Yong Ki; Bae, Young Tae

2000-01-01

The aim of this study was to investigate whether Tc-99m MIBI scintimammography (SMM) provide more information than contrast enhanced MRI in highly suspected breast cancer patients. This study included 32 breast lesions of 29 highly suspected patients having breast cancer. All patients were performed SMM and contrast enhanced MRI. The SMMs and contrast enhanced MRI were correlated with histopathologic results. Thirty breast lesions were diagnosed malignant diseases and 2 were diagnosed benign diseases. SMM showed 29 true positives (TP), 1 true negative (TN), 1 false positive (FP), and 1 false negative (FN). The sensitivity was 96.6%. Contrast enhanced MRI revealed 24 TP, 0 TN, 1 FP, 3 FN and 4 indeterminate cases. The sensitivity was 88.8%. In the assessment of axillary lymph node metastasis, SMM showed 9 TP, 10 TN, 0 FP, and 3 FN. The sensitivity and specificity were 75% and 100%. Contrast enhanced MRI revealed 6 TP, 9 TN, 1 FP, and 6 FN. The sensitivity and specificity were 50% and 90%. Among 4 indeterminate cases with MRI findings, SMM correctly diagnosed malignant breast diseases in 3 lesions. However, SMM showed false positive in 1 lesion. SMM could correctly diagnosed malignant breast diseases more 5 lesions than contrast enhanced MRI. SMM revealed higher sensitivity in detection of primary breast cancer and axillary LN metastasis than contrast enhanced MRI. SMMs could correctly diagnosed malignant breast diseases even if the MRI showed indeterminate findings. In highly suspected patients having breast cancer, SMM may provide additive information in detection of breast cancer if contrast enhanced MRI showed indeterminate findings but this is to be determined later by large population based study

Multiparametric MR imaging of the breast after augmentation and oncoplastic surgery

International Nuclear Information System (INIS)

Ivanov, V.; Kirova, G.

2015-01-01

Full text: Evaluation of breast lesions in patients after augmentation and oncoplastic surgery are difficult and uncertain with ultrasound and mammography. These two methods give us information of the lesions nature, but this information has low specificity. Morphologic MRI sequences enable to an exact assessment the nature of the lesions high sensitivity, but with low specificity. To enhance security in the evaluation of the lesions new series as DCE MRI, DWI and MRI proton spectroscopy have to be added. Teaching points: to learn how and when to use multiparametric MRI for evaluation of breast lesion after augmentation and oncoplastic surgery; to present the multiparametric MRI protocol for evaluation of malignant breast lesion after augmentation and oncoplastic surgery; to discuss the main signs differentiating benign from malignant breast lesions based on the features on multiparametric MR Inconclusive data from mammography, ultrasound and standard morphological MR series (T1,T2, FAT SAT) in the estimation of changes after augmentation and oncoplastic surgery require the use of multiparametric MRI analysis as a supplementary method for increasing sensitivity and specificity of breast MRI

Use of shear wave elastography to differentiate benign and malignant breast lesions.

Science.gov (United States)

Çebi Olgun, Deniz; Korkmazer, Bora; Kılıç, Fahrettin; Dikici, Atilla Süleyman; Velidedeoğlu, Mehmet; Aydoğan, Fatih; Kantarcı, Fatih; Yılmaz, Mehmet Halit

2014-01-01

We aimed to determine the correlations between the elasticity values of solid breast masses and histopathological findings to define cutoff elasticity values differentiating malignant from benign lesions. A total of 115 solid breast lesions of 109 consecutive patients were evaluated prospectively using shear wave elastography (SWE). Two orthogonal elastographic images of each lesion were obtained. Minimum, mean, and maximum elasticity values were calculated in regions of interest placed over the stiffest areas on the two images; we also calculated mass/fat elasticity ratios. Correlation of elastographic measurements with histopathological results were studied. Eighty-three benign and thirty-two malignant lesions were histopathologically diagnosed. The minimum, mean, and maximum elasticity values, and the mass/fat elasticity ratios of malignant lesions, were significantly higher than those of benign lesions. The cutoff value was 45.7 kPa for mean elasticity (sensitivity, 96%; specificity, 95%), 54.3 kPa for maximum elasticity (sensitivity, 95%; specificity, 94%), 37.1 kPa for minimum elasticity (sensitivity, 96%; specificity, 95%), and 4.6 for the mass/fat elasticity ratio (sensitivity, 97%; specificity, 95%). SWE yields additional valuable quantitative data to ultrasonographic examination on solid breast lesions. SWE may serve as a complementary tool for diagnosis of breast lesions. Long-term clinical studies are required to accurately select lesions requiring biopsy.

Accuracy of Self-Reported Breast Cancer Information among Women from the Ontario Site of the Breast Cancer Family Registry

International Nuclear Information System (INIS)

Barisic, A.; Glendon, G.; Andrulis, I. L.; Knight, J. A.; Barisic, A.; Knight, J. A.; Glendon, G.; Weerasooriya, N.; Andrulis, I. L.

2012-01-01

Obtaining complete medical record information can be challenging and expensive in breast cancer studies. The current literature is limited with respect to the accuracy of self-report and factors that may influence this. We assessed the agreement between self-reported and medical record breast cancer information among women from the Ontario site of the Breast Cancer Family Registry. Women aged 20-69 years diagnosed with incident breast cancer 1996-1998 were identified from the Ontario Cancer Registry, sampled on age and family history. We calculated kappa statistics, proportion correct, sensitivity, specificity, and positive and negative predictive values and conducted unconditional logistic regression to examine whether characteristics of the women influenced agreement. The proportions of women who correctly reported having received a broad category of therapy (hormone therapy, chemotherapy, radiation, or surgery) as well as sensitivity and specificity were above 90%, and the kappa statistics were above 0.80. The specific type of hormonal or chemotherapy was reported with low-to-moderate agreement. Aside from recurrence, no factors were consistently associated with agreement. Thus, most women were able to accurately report broad categories of treatment but not necessarily specific treatment types. The finding of this study can aid researchers in the use and design of self-administered treatment questionnaires

Combined SPECT/CT and PET/CT for breast imaging

Energy Technology Data Exchange (ETDEWEB)

Russo, Paolo [Università di Napoli Federico II, Dipartimento di Fisica, Via Cintia, Naples I-80126 (Italy); INFN Sezione di Napoli, Via Cintia, Naples I-80126 (Italy); Larobina, Michele [Istituto di Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerche, Via Tommaso De Amicis, 95, Naples I-80145 (Italy); Di Lillo, Francesca [Università di Napoli Federico II, Dipartimento di Fisica, Via Cintia, Naples I-80126 (Italy); INFN Sezione di Napoli, Via Cintia, Naples I-80126 (Italy); Del Vecchio, Silvana [Università di Napoli Federico II, Dipartimento di Scienze Biomediche Avanzate, Via Pansini, 5, Naples I-80131 (Italy); Mettivier, Giovanni, E-mail: mettivier@na.infn.it [Università di Napoli Federico II, Dipartimento di Fisica, Via Cintia, Naples I-80126 (Italy); INFN Sezione di Napoli, Via Cintia, Naples I-80126 (Italy)

2016-02-11

In the field of nuclear medicine imaging, breast imaging for cancer diagnosis is still mainly based on 2D imaging techniques. Three-dimensional tomographic imaging with whole-body PET or SPECT scanners, when used for imaging the breast, has performance limits in terms of spatial resolution and sensitivity, which can be overcome only with a dedicated instrumentation. However, only few hybrid imaging systems for PET/CT or SPECT/CT dedicated to the breast have been developed in the last decade, providing complementary functional and anatomical information on normal breast tissue and lesions. These systems are still under development and clinical trials on just few patients have been reported; no commercial dedicated breast PET/CT or SPECT/CT is available. This paper reviews combined dedicated breast PET/CT and SPECT/CT scanners described in the recent literature, with focus on their technological aspects.

Integrated analysis of breast cancer cell lines reveals unique signaling pathways

Energy Technology Data Exchange (ETDEWEB)

Heiser, Laura M.; Wang, Nicholas J.; Talcott, Carolyn L.; Laderoute, Keith R.; Knapp, Merrill; Guan, Yinghui; Hu, Zhi; Ziyad, Safiyyah; Weber, Barbara L.; Laquerre, Sylvie; Jackson, Jeffrey R.; Wooster, Richard F.; Kuo, Wen-Lin; Gray, Joe W.; Spellman, Paul T.

2009-03-31

Cancer is a heterogeneous disease resulting from the accumulation of genetic defects that negatively impact control of cell division, motility, adhesion and apoptosis. Deregulation in signaling along the EGFR-MAPK pathway is common in breast cancer, though the manner in which deregulation occurs varies between both individuals and cancer subtypes. We were interested in identifying subnetworks within the EGFR-MAPK pathway that are similarly deregulated across subsets of breast cancers. To that end, we mapped genomic, transcriptional and proteomic profiles for 30 breast cancer cell lines onto a curated Pathway Logic symbolic systems model of EGFR-MEK signaling. This model was comprised of 539 molecular states and 396 rules governing signaling between active states. We analyzed these models and identified several subtype specific subnetworks, including one that suggested PAK1 is particularly important in regulating the MAPK cascade when it is over-expressed. We hypothesized that PAK1 overexpressing cell lines would have increased sensitivity to MEK inhibitors. We tested this experimentally by measuring quantitative responses of 20 breast cancer cell lines to three MEK inhibitors. We found that PAK1 over-expressing luminal breast cancer cell lines are significantly more sensitive to MEK inhibition as compared to those that express PAK1 at low levels. This indicates that PAK1 over-expression may be a useful clinical marker to identify patient populations that may be sensitive to MEK inhibitors. All together, our results support the utility of symbolic system biology models for identification of therapeutic approaches that will be effective against breast cancer subsets.

Integrated analysis of breast cancer cell lines reveals unique signaling pathways.

Science.gov (United States)

Heiser, Laura M; Wang, Nicholas J; Talcott, Carolyn L; Laderoute, Keith R; Knapp, Merrill; Guan, Yinghui; Hu, Zhi; Ziyad, Safiyyah; Weber, Barbara L; Laquerre, Sylvie; Jackson, Jeffrey R; Wooster, Richard F; Kuo, Wen Lin; Gray, Joe W; Spellman, Paul T

2009-01-01

Cancer is a heterogeneous disease resulting from the accumulation of genetic defects that negatively impact control of cell division, motility, adhesion and apoptosis. Deregulation in signaling along the EgfR-MAPK pathway is common in breast cancer, though the manner in which deregulation occurs varies between both individuals and cancer subtypes. We were interested in identifying subnetworks within the EgfR-MAPK pathway that are similarly deregulated across subsets of breast cancers. To that end, we mapped genomic, transcriptional and proteomic profiles for 30 breast cancer cell lines onto a curated Pathway Logic symbolic systems model of EgfR-MAPK signaling. This model was composed of 539 molecular states and 396 rules governing signaling between active states. We analyzed these models and identified several subtype-specific subnetworks, including one that suggested Pak1 is particularly important in regulating the MAPK cascade when it is over-expressed. We hypothesized that Pak1 over-expressing cell lines would have increased sensitivity to Mek inhibitors. We tested this experimentally by measuring quantitative responses of 20 breast cancer cell lines to three Mek inhibitors. We found that Pak1 over-expressing luminal breast cancer cell lines are significantly more sensitive to Mek inhibition compared to those that express Pak1 at low levels. This indicates that Pak1 over-expression may be a useful clinical marker to identify patient populations that may be sensitive to Mek inhibitors. All together, our results support the utility of symbolic system biology models for identification of therapeutic approaches that will be effective against breast cancer subsets.

Tuberculosis of the breast

Directory of Open Access Journals (Sweden)

Baharoon Salim

2008-01-01

Full Text Available Tuberculosis of the breast is an uncommon disease even in countries where the incidence of pulmonary and extrapulmonary tuberculosis is high. Clinical presentation is usually of a solitary, ill-defined, unilateral hard lump situated in the upper outer quadrant of the breast. This disease can present a diagnostic problem on radiological and microbiological investigations, and thus a high index of suspicion is needed. Incorporating a highly sensitive technique like polymerase chain reaction (PCR may be helpful in establishing the usefulness of such technology and can aid in conforming the diagnosis early. The disease is curable with antitubercular drugs, and surgery is rarely required

Population Viability and Vital Rate Sensitivity of an Endangered Avian Cooperative Breeder, the White-Breasted Thrasher (Ramphocinclus brachyurus.

Directory of Open Access Journals (Sweden)

Jennifer L Mortensen

Full Text Available Social behaviors can significantly affect population viability, and some behaviors might reduce extinction risk. We used population viability analysis to evaluate effects of past and proposed habitat loss on the White-breasted Thrasher (Ramphocinclus brachyurus, a cooperatively breeding songbird with a global population size of <2000 individuals. We used an individual-based approach to build the first demographic population projection model for this endangered species, parameterizing the model with data from eight years of field study before and after habitat loss within the stronghold of the species' distribution. The recent habitat loss resulted in an approximately 18% predicted decline in population size; this estimate was mirrored by a separate assessment using occupancy data. When mortality rates remained close to the pre-habitat loss estimate, quasi-extinction probability was low under extant habitat area, but increased with habitat loss expected after current plans for resort construction are completed. Post-habitat loss mortality rate estimates were too high for projected populations to persist. Vital rate sensitivity analyses indicated that population growth rate and population persistence were most sensitive to juvenile mortality. However, observed values for adult mortality were closest to the threshold value above which populations would crash. Adult mortality, already relatively low, may have the least capacity to change compared to other vital rates, whereas juvenile mortality may have the most capacity for improvement. Results suggest that improving mortality estimates and determining the cause(s of juvenile mortality should be research priorities. Despite predictions that aspects of cooperative systems may result in variation in reproduction or juvenile mortality being the most sensitive vital rates, adult mortality was the most sensitive in half of the demographic models of other avian cooperative breeders. Interestingly, vital

Magnetic resonance imaging of the breast: current indications

International Nuclear Information System (INIS)

Lalonde, L.; David, J.; Trop, I.

2005-01-01

Breast magnetic resonance imaging (MRI) plays an increasing role in the management of selecting breast cancer patients. MRI is recognized as the most sensitive modality for the detection of invasive breast cancer. Several valuable clinical applications of MRI have emerged for breast cancer detection and diagnosis from clinical investigations. Breast MRI is helpful for women diagnosed with breast cancer who contemplate breast conserving surgery; it provides valuable information on the extent of the disease. MRI can also help assess for residual invasive cancer in patients who have undergone lumpectomy with positive margins at pathology. It is very reliable in differentiating scar tissue from recurrence at the lumpectomy site. MRI is also reliable in finding a breast cancer in women with axillary nodal metastases and unknown primary tumour. MRI can help to monitor the response to chemotherapy. Breast MRI could be a better screening tool than mammography in women with very high risks of developing breast cancer, such as breast cancer gene carriers and patients treated with chest radiation. Other potential uses of MRI include evaluation of the integrity of silicone breast implants and evaluation of the parenchyma in women with silicone gel implants or free injection of silicone gel. However, like any other technique, breast MRI has some drawbacks, including low-to-moderate specificity, high costs, and variability in technique and interpretation. Radiologists must have a clear understanding of valid indications and selection criteria to use this technique appropriately. (author)

Preoperative axillary lymph node evaluation in breast cancer patients by breast magnetic resonance imaging (MRI): Can breast MRI exclude advanced nodal disease?

International Nuclear Information System (INIS)

Hyun, Su Jeong; Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; Kim, Min Jung

2016-01-01

To evaluate the diagnostic performance of breast magnetic resonance imaging (MRI) in preoperative evaluation of axillary lymph node metastasis (ALNM) in breast cancer patients and to assess whether breast MRI can be used to exclude advanced nodal disease. A total of 425 patients were included in this study and breast MRI findings were retrospectively reviewed. The diagnostic performance of breast MRI for diagnosis of ALNM was evaluated in all patients, patients with neoadjuvant chemotherapy (NAC), and those without NAC (no-NAC). We evaluated whether negative MRI findings (cN0) can exclude advanced nodal disease (pN2-pN3) using the negative predictive value (NPV) in each group. The sensitivity and NPV of breast MRI in evaluation of ALNM was 51.3 % (60/117) and 83.3 % (284/341), respectively. For cN0 cases on MRI, pN2-pN3 manifested in 1.8 % (6/341) of the overall patients, 0.4 % (1/257) of the no-NAC group, and 6 % (5/84) of the NAC group. The NPV of negative MRI findings for exclusion of pN2-pN3 was higher for the no-NAC group than for the NAC group (99.6 % vs. 94.0 %, p = 0.039). Negative MRI findings (cN0) can exclude the presence of advanced nodal disease with an NPV of 99.6 % in the no-NAC group. (orig.)

Preoperative axillary lymph node evaluation in breast cancer patients by breast magnetic resonance imaging (MRI): Can breast MRI exclude advanced nodal disease?

Energy Technology Data Exchange (ETDEWEB)

Hyun, Su Jeong [Yonsei University College of Medicine, Department of Radiology, Breast Cancer Clinic, Severance Hospital, Research Institute of Radiological Science, Seoul (Korea, Republic of); Hallym University Medical Center, Department of Radiology, Kangnam Sacred Heart Hospital, Seoul (Korea, Republic of); Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; Kim, Min Jung [Yonsei University College of Medicine, Department of Radiology, Breast Cancer Clinic, Severance Hospital, Research Institute of Radiological Science, Seoul (Korea, Republic of)

2016-11-15

To evaluate the diagnostic performance of breast magnetic resonance imaging (MRI) in preoperative evaluation of axillary lymph node metastasis (ALNM) in breast cancer patients and to assess whether breast MRI can be used to exclude advanced nodal disease. A total of 425 patients were included in this study and breast MRI findings were retrospectively reviewed. The diagnostic performance of breast MRI for diagnosis of ALNM was evaluated in all patients, patients with neoadjuvant chemotherapy (NAC), and those without NAC (no-NAC). We evaluated whether negative MRI findings (cN0) can exclude advanced nodal disease (pN2-pN3) using the negative predictive value (NPV) in each group. The sensitivity and NPV of breast MRI in evaluation of ALNM was 51.3 % (60/117) and 83.3 % (284/341), respectively. For cN0 cases on MRI, pN2-pN3 manifested in 1.8 % (6/341) of the overall patients, 0.4 % (1/257) of the no-NAC group, and 6 % (5/84) of the NAC group. The NPV of negative MRI findings for exclusion of pN2-pN3 was higher for the no-NAC group than for the NAC group (99.6 % vs. 94.0 %, p = 0.039). Negative MRI findings (cN0) can exclude the presence of advanced nodal disease with an NPV of 99.6 % in the no-NAC group. (orig.)

Early detection of breast cancer: benefits and risks of supplemental breast ultrasound in asymptomatic women with mammographically dense breast tissue. A systematic review

International Nuclear Information System (INIS)

Nothacker, Monika; Duda, Volker; Hahn, Markus; Warm, Mathias; Degenhardt, Friedrich; Madjar, Helmut; Weinbrenner, Susanne; Albert, Ute-Susann

2009-01-01

the application to women age 50-69 years as proposed for mammographic screening could result in less striking benefit. Further validation studies should employ a uniform assessment system such as BI-RADS and report not only PPV, but also negative predictive value, sensitivity and specificity. Supplemental breast ultrasound in the population of women with mammographically dense breast tissue (ACR 3 and 4) permits detection of small, otherwise occult, breast cancers. Potential adverse impacts for women in this intermediate risk group are associated with an increased biopsy rate

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

Science.gov (United States)

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

Neratinib overcomes trastuzumab resistance in HER2 amplified breast cancer.

OpenAIRE

Canonici, A; Gijsen, M; Mullooly, M; Bennett, R; Bouguern, N; Pedersen, K; O'Brien, NA; Roxanis, I; Li, J-L; Bridge, E; Finn, R; Siamon, D; McGowan, P; Duffy, MJ; O'Donovan, N

2013-01-01

Trastuzumab has been shown to improve the survival outcomes of HER2 positive breast cancer patients. However, a significant proportion of HER2-positive patients are either inherently resistant or develop resistance to trastuzumab. We assessed the effects of neratinib, an irreversible panHER inhibitor, in a panel of 36 breast cancer cell lines. We further assessed its effects with or without trastuzumab in several sensitive and resistant breast cancer cells as well as a BT474 xenograft model. ...

Iranian Women's Breast Health-Seeking Behaviors: Husband's Role.

Science.gov (United States)

Mazloomy-Mahmoodabad, Seyed Saeed; Khodayarian, Mahsa; Morowatisharifabad, Mohammad Ali; Lamyian, Minoor; Tavangar, Hossein

2017-12-14

Breast cancer has become the most common cancer among Yazdi women in Iran. Thus, it is necessary to encourage these women to participate in breast health-seeking behaviors. In this regard, husbands can play an effective role. The aim of this study was to explore women's perceptions about the effect of their husband's role on breast health-seeking protection motivation. This study used a directed qualitative content analysis approach based on the Protection Motivation Theory. Participants were selected using purposive sampling; in-depth semistructured interviews with 14 Yazdi women were completed. One major category named "motivator role of husband" emerged from the analysis. The following subcategories underlying this category were "indifference and a lack of support as long as the women can continue with expected duties," "what women want for support," "facilitating and restrictive factors of husband's supportive role," "public health education needed," and "husband's agreement with preventive actions." Voluntary participation in breast health-seeking behaviors is a culturally sensitive topic. The qualitative methodology allowed this sensitive topic and its different aspects to be explored. The findings indicated that the major source of support for women was their husband's behavior toward breast health-seeking actions. Family cohesion and love among couples were identified as strong determinant factors pertaining to husband's supportive behaviors. The study findings provided deeper understanding about the effective factors related to a husband's role in motivating a wife to practice breast cancer prevention. These new findings are relevant for health educators and practitioners to develop culturally based interventions.

Lanthanum gallate and ceria composite as electrolyte for solid oxide fuel cells

Energy Technology Data Exchange (ETDEWEB)

Li Shuai, E-mail: shuail@kth.s [Department of Materials Science and Engineering, School of Industrial Engineering and Management, Royal Institute of Technology, SE 10044 Stockholm (Sweden); Li Zhicheng [School of Materials Science and Engineering, Central South University, 410083 Changsha, Hunan (China); Bergman, Bill [Department of Materials Science and Engineering, School of Industrial Engineering and Management, Royal Institute of Technology, SE 10044 Stockholm (Sweden)

2010-03-04

The composite of doped lanthanum gallate (La{sub 0.9}Sr{sub 0.1}Ga{sub 0.8}Mg{sub 0.2}O{sub 2.85}, LSGM) and doped ceria (Ce{sub 0.8}Sm{sub 0.2}O{sub 1.9}, CSO) was investigated as an electrolyte for solid oxide fuel cell (SOFC). The LSGM-CSO composite was examined by X-ray diffraction (XRD) and impedance spectroscopy. It was found that the sintered LSGM-CSO composite contains mainly fluorite CeO{sub 2} phase and a minority impurity phase, Sm{sub 3}Ga{sub 5}O{sub 12}. The LSGM-CSO composite electrolyte shows a small grain boundary response in the impedance spectroscopy as compared to LSGM and CSO pellets. The composite electrolyte exhibits the highest conductivity in the temperature range of 250-600 {sup o}C, compared to LSGM and CSO. The LSGM-CSO composite can be expected to be an attractive intermediate temperature electrolyte material for solid oxide fuel cells.

Induction of apoptosis by epigallocatechin-3-gallate in human lymphoblastoid B cells

International Nuclear Information System (INIS)

Noda, Chiseko; He, Jinsong; Takano, Tomoko; Tanaka, Chisato; Kondo, Toshinori; Tohyama, Kaoru; Yamamura, Hirohei; Tohyama, Yumi

2007-01-01

(-)-Epigallocatechin-3-gallate (EGCG), a major constituent of green tea polyphenols, has been shown to suppress cancer cell proliferation and induce apoptosis. In this study we investigated its efficacy and the mechanism underlying its effect using human B lymphoblastoid cell line Ramos, and effect of co-treatment with EGCG and a chemotherapeutic agent on apoptotic cell death. EGCG induced dose- and time-dependent apoptotic cell death accompanied by loss of mitochondrial transmembrane potential, release of cytochrome c into the cytosol, and cleavage of pro-caspase-9 to its active form. EGCG also enhanced production of intracellular reactive oxygen species (ROS). Pretreatment with diphenylene iodonium chloride, an inhibitor of NAD(P)H oxidase and an antioxidant, partially suppressed both EGCG-induced apoptosis and production of ROS, implying that oxidative stress is involved in the apoptotic response. Furthermore, we showed that combined-treatment with EGCG and a chemotherapeutic agent, etoposide, synergistically induced apoptosis in Ramos cells

Mechanisms of saccharide protection against epigallocatechin-3-gallate deterioration in aqueous solutions.

Science.gov (United States)

Shpigelman, Avi; Zisapel, Adi; Cohen, Yifat; Livney, Yoav D

2013-08-15

We investigated the mechanisms of the protection conferred by sugars to epigallocatechin-3-gallate (EGCG) against deterioration. Additionally, we present a rapid method for evaluating the deterioration rate of EGCG using absorbance spectroscopy. We found that various sugars provided different levels of protection at identical weight percentage, and the combination of sugars and β-lactoglobulin nanocomplexes provided greater protection for EGCG than each protective component alone. We suggest that the concentration-dependent protection by sugars resulted from a combination of mechanisms, including: (1) reduced aqueous O2 solubility, (2) scavenging of reactive oxygen species, and (3) chelation of traces of transition metal ions, which is suggested to be the main reason for the differences among the sugars. The observed protective effect of sugars can be easily applied by the industry in proper selection of sugars for enrichment of syrups or concentrates with EGCG and for the preparation of enriched beverages and foods for health promotion. Copyright © 2013 Elsevier Ltd. All rights reserved.

Neratinib overcomes trastuzumab resistance in HER2 amplified breast cancer.

Science.gov (United States)

Canonici, Alexandra; Gijsen, Merel; Mullooly, Maeve; Bennett, Ruth; Bouguern, Noujoude; Pedersen, Kasper; O'Brien, Neil A; Roxanis, Ioannis; Li, Ji-Liang; Bridge, Esther; Finn, Richard; Siamon, Dennis; McGowan, Patricia; Duffy, Michael J; O'Donovan, Norma; Crown, John; Kong, Anthony

2013-10-01

Trastuzumab has been shown to improve the survival outcomes of HER2 positive breast cancer patients. However, a significant proportion of HER2-positive patients are either inherently resistant or develop resistance to trastuzumab. We assessed the effects of neratinib, an irreversible panHER inhibitor, in a panel of 36 breast cancer cell lines. We further assessed its effects with or without trastuzumab in several sensitive and resistant breast cancer cells as well as a BT474 xenograft model. We confirmed that neratinib was significantly more active in HER2-amplified than HER2 non-amplified cell lines. Neratinib decreased the activation of the 4 HER receptors and inhibited downstream pathways. However, HER3 and Akt were reactivated at 24 hours, which was prevented by the combination of trastuzumab and neratinib. Neratinib also decreased pHER2 and pHER3 in acquired trastuzumab resistant cells. Neratinib in combination with trastuzumab had a greater growth inhibitory effect than either drug alone in 4 HER2 positive cell lines. Furthermore, trastuzumab in combination with neratinib was growth inhibitory in SKBR3 and BT474 cells which had acquired resistance to trastuzumab as well as in a BT474 xenograft model. Innately trastuzumab resistant cell lines showed sensitivity to neratinib, but the combination did not enhance response compared to neratinib alone. Levels of HER2 and phospho-HER2 showed a direct correlation with sensitivity to neratinib. Our data indicate that neratinib is an effective anti-HER2 therapy and counteracted both innate and acquired trastuzumab resistance in HER2 positive breast cancer. Our results suggest that combined treatment with trastuzumab and neratinib is likely to be more effective than either treatment alone for both trastuzumab-sensitive breast cancer as well as HER2-positive tumors with acquired resistance to trastuzumab.

Is axillary sonographic staging less accurate in invasive lobular breast cancer than in ductal breast cancer?

Science.gov (United States)

Sankaye, Prashant; Chhatani, Sharmila; Porter, Gareth; Steel, Jim; Doyle, Sarah

2014-10-01

The purpose of this study was to determine whether axillary sonography is less accurate in invasive lobular breast cancer than in ductal breast cancer. Patients with invasive breast cancer were retrospectively identified from histologic records from 2010 to 2012. Staging axillary sonograms from 96 patients with primary breast cancer in each of 2 subgroups, invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC), were reviewed. Preoperative sonographically guided 14-gauge core biopsy was performed on morphologically abnormal lymph nodes. Thirty-one of 96 patients (32%) in each subgroup were node positive on final postoperative histopathologic analysis. Axillary staging sensitivity was 17 of 31 patients (54%) in the IDC subgroup and 15 of 31(48%) in the ILC subgroup. Further analysis of the data showed no statistically significant differences between these subgroups. We found that there was no statistically significant difference in the accuracy of axillary sonographic staging between ILC and IDC. © 2014 by the American Institute of Ultrasound in Medicine.

Validation of a measurement tool to assess awareness of breast cancer.

Science.gov (United States)

Linsell, Louise; Forbes, Lindsay J L; Burgess, Caroline; Kapari, Marcia; Thurnham, Angela; Ramirez, Amanda J

2010-05-01

Until now, there has been no universally accepted and validated measure of breast cancer awareness. This study aimed to validate the new Breast Cancer Awareness Measure (BCAM) which assesses, using a self-complete questionnaire, knowledge of breast cancer symptoms and age-related risk, and frequency of breast checking. We measured the psychometric properties of the BCAM in 1035 women attending the NHS Breast Screening Programme: acceptability was assessed using a feedback questionnaire (n=292); sensitivity to change after an intervention promoting breast cancer awareness (n=576), and test-retest reliability (n=167). We also assessed readability, and construct validity using the 'known-groups' method. The readability of the BCAM was high. Over 90% of women found it acceptable. The BCAM was sensitive to change: there was an increase in the proportion of women obtaining the full score for breast cancer awareness one month after receiving the intervention promoting breast cancer awareness; this was greater among those who received a more intensive version (less intensive version (booklet): 9.3%, 95% confidence interval (CI): 4.5-14.1%; more intensive version (interaction with health professional plus booklet): 30%, 95% CI: 23.4-36.6%). Test-retest reliability of the BCAM was moderate to good for most items. Cancer experts had higher levels of cancer awareness than non-medical academics (50% versus 6%, p=0.001), indicating good construct validity. The BCAM is a valid and robust measure of breast cancer awareness suitable for use in surveys of breast cancer awareness in the general population and to evaluate the impact of awareness-raising interventions. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

GENOMIC PREDICTOR OF RESPONSE AND SURVIVAL FOLLOWING TAXANE-ANTHRACYCLINE CHEMOTHERAPY FOR INVASIVE BREAST CANCER

Science.gov (United States)

Hatzis, Christos; Pusztai, Lajos; Valero, Vicente; Booser, Daniel J.; Esserman, Laura; Lluch, Ana; Vidaurre, Tatiana; Holmes, Frankie; Souchon, Eduardo; Martin, Miguel; Cotrina, José; Gomez, Henry; Hubbard, Rebekah; Chacón, J. Ignacio; Ferrer-Lozano, Jaime; Dyer, Richard; Buxton, Meredith; Gong, Yun; Wu, Yun; Ibrahim, Nuhad; Andreopoulou, Eleni; Ueno, Naoto T.; Hunt, Kelly; Yang, Wei; Nazario, Arlene; DeMichele, Angela; O’Shaughnessy, Joyce; Hortobagyi, Gabriel N.; Symmans, W. Fraser

2017-01-01

CONTEXT Accurate prediction of who will (or won’t) have high probability of survival benefit from standard treatments is fundamental for individualized cancer treatment strategies. OBJECTIVE To develop a predictor of response and survival from chemotherapy for newly diagnosed invasive breast cancer. DESIGN Development of different predictive signatures for resistance and response to neoadjuvant chemotherapy (stratified according to estrogen receptor (ER) status) from gene expression microarrays of newly diagnosed breast cancer (310 patients). Then prediction of breast cancer treatment-sensitivity using the combination of signatures for: 1) sensitivity to endocrine therapy, 2) chemo-resistance, and 3) chemo-sensitivity. Independent validation (198 patients) and comparison with other reported genomic predictors of chemotherapy response. SETTING Prospective multicenter study to develop and test genomic predictors for neoadjuvant chemotherapy. PATIENTS Newly diagnosed HER2-negative breast cancer treated with chemotherapy containing sequential taxane and anthracycline-based regimens then endocrine therapy (if hormone receptor-positive). MAIN OUTCOME MEASURES Distant relapse-free survival (DRFS) if predicted treatment-sensitive and absolute risk reduction (ARR, difference in DRFS of the two predicted groups) at median follow-up (3 years), and their 95% confidence intervals (CI). RESULTS Patients in the independent validation cohort (99% clinical Stage II–III) who were predicted to be treatment-sensitive (28% of total) had DRFS of 92% (CI 85–100) and survival benefit compared to others (absolute risk reduction (ARR) 18%; CI 6–28). Predictions were accurate if breast cancer was ER-positive (30% predicted sensitive, DRFS 97%, CI 91–100; ARR 11%, CI 0.1–21) or ER-negative (26% predicted sensitive, DRFS 83%, CI 68–100; ARR 26%, CI 4–28), and were significant in multivariate analysis after adjusting for relevant clinical-pathologic characteristics. Other

The Use of Chlorhexidine/n-Propyl Gallate (CPG) as an Ambient-Temperature Urine Preservative

Science.gov (United States)

Nillen, Jeannie L.; Smith, Scott M.

2003-01-01

A safe, effective ambient temperature urine preservative, chlorhexidine/n-propyl gallate (CPG), has been formulated for use during spacefli ght that reduces the effects of oxidation and bacterial contamination on sample integrity while maintaining urine pH. The ability of this preservative to maintain stability of nine key analytes was evaluated for a period of one year. CPG effectively maintained stability of a mmonia, total nitrogen, 3-methylhistidine, chloride, sodium, potassiu m, and urea; however, creatinine and osmolality were not preserved by CPG. These data indicate that CPG offers prolonged room-temperature storage for multiple urine analytes, reducing the requirements for f rozen urine storage on future spaceflights. Iii medical applications on Earth, this technology can allow urine samples to be collected in remote settings and eliminate the need to ship frozen samples.

Mammographic compression after breast conserving therapy: Controlling pressure instead of force

International Nuclear Information System (INIS)

Groot, J. E. de; Branderhorst, W.; Grimbergen, C. A.; Broeders, M. J. M.; Heeten, G. J. den

2014-01-01

Purpose: X-ray mammography is the primary tool for early detection of breast cancer and for follow-up after breast conserving therapy (BCT). BCT-treated breasts are smaller, less elastic, and more sensitive to pain. Instead of the current force-controlled approach of applying the same force to each breast, pressure-controlled protocols aim to improve standardization in terms of physiology by taking breast contact area and inelasticity into account. The purpose of this study is to estimate the potential for pressure protocols to reduce discomfort and pain, particularly the number of severe pain complaints for BCT-treated breasts. Methods: A prospective observational study including 58 women having one BCT-treated breast and one untreated nonsymptomatic breast, following our hospital's 18 decanewton (daN) compression protocol was performed. Breast thickness, applied force, contact area, mean pressure, breast volume, and inelasticity (mean E-modulus) were statistically compared between the within-women breast pairs, and data were used as predictors for severe pain, i.e., scores 7 and higher on an 11-point Numerical Rating Scale. Curve-fitting models were used to estimate how pressure-controlled protocols affect breast thickness, compression force, and pain experience. Results: BCT-treated breasts had on average 27% smaller contact areas, 30% lower elasticity, and 30% higher pain scores than untreated breasts (allp 2 decrease in contact area, as well as increased pain sensitivity, BCT-breasts had on average 5.3 times higher odds for severe pain than untreated breasts. Model estimations for a pressure-controlled protocol with a 10 kPa target pressure, which is below normal arterial pressure, suggest an average 26% (range 10%–36%) reduction in pain score, and an average 77% (range 46%–95%) reduction of the odds for severe pain. The estimated increase in thickness is +6.4% for BCT breasts. Conclusions: After BCT, women have hardly any choice in avoiding an annual

Efficacy of storage phosphor-based digital mammography in diagnosis of breast cancer

International Nuclear Information System (INIS)

Kitahama, Hiroyuki

1991-01-01

The aim of this study is to present efficacy of storage phosphor-based digital mammography (CR-mammography) in diagnosis of breast cancer. Ninety-seven cases with breast cancer including 44 cases less than 2 cm in macroscopic size (t1 cases) were evaluated using storage phosphor-based digital mammography (2000 x 2510 pixels by 10 bits). Abnormal findings on CR-mammography were detected in 86 cases (88.7%) of 97 women with breast cancer. Sensitivity of CR-mammography was 88.7%. It was superior to that of film-screen mammography. On t1 breast cancer cases, sensitivity on CR-mammography was 88.6%. False negative rate in t1 breast cancer cases was reduced by image processing using CR-mammography. To evaluate microcalcifications, CR-mammograms and film-screen mammograms were investigated in 22 cases of breast cancer proven pathologically the existence of microcalcifications and 11 paraffin tissue blocks of breast cancer. CR-mammography was superior to film-screen mammography in recognizing of microcalcifications. As regards the detectability for the number and the shape of microcalcifications, CR-mammography was equivalent to film-screen mammography. Receiver operating characteristic (ROC) analysis by eight observers was performed for CR-mammography and film-screen mammography with 54 breast cancer patients and 54 normal cases. The detectability of abnormal findings of breast cancer on CR-mammography (ROC area=0.91) was better than that on film-screen mammography (ROC area=0.88) (p<0.05). Efficacy of storage phosphor-based digital mammography in diagnosis of breast cancer was discussed and demonstrated in this study. (author)

Effectiveness of ultrasonography for diagnosis of breast cancer according to detection opportunity

International Nuclear Information System (INIS)

Yasuda, Jun; Kamada, Hidetoshi; Goto, Takeshi

2007-01-01

One hundred eighty-five cases of primary breast cancer cases treated surgically at our hospital between January 2001 and December 2005 were divided into three groups based on the disease state at the time of discovery. These three groups included 40 asymptomatic cases detected by breast cancer screening (screening group), 23 cases of benign conditions detected at follow-up (follow-up group), and 122 cases detected as a result of symptoms (symptomatic group). These groups were then evaluated retrospectively to assess the usefulness of ultrasonography (US) for breast cancer detection. The average tumor diameter was 14.0 mm in the screening group, 10.8 mm in the follow-up group, and 24.6 mm in the symptomatic group. In these groups, the sensitivity of US was 90.0%, 95.7%, and 100%, respectively, when each category over 3 was considered as positive. The sensitivity of mammography (MMG) was 85.0%, 73.9%, and 96.7%, respectively. Among three cases that were false-negative by US, two were due only to microcalcification and all three were categorized as 2. The average tumor diameter in 16 cases that were false-negative by MMG was 12.9 mm, and all were invasive cancers. The present results indicate that the sensitivity of US is superior to that of MMG for diagnosis of breast cancer. Regular follow-up using US is thought to contribute to the early detection of small invasive cancers. US is complementary to MMG for detection of breast cancer, and therefore the two techniques together are thought to provide better screening sensitivity. (author)

Novel anticancer activity of phloroglucinol against breast cancer stem-like cells

Energy Technology Data Exchange (ETDEWEB)

Kim, Rae-Kwon; Uddin, Nizam [Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Hyun, Jin-Won [College of Medicine and Applied Radiological Science Research Institute, Jeju National University, Jeju-si 690-756 (Korea, Republic of); Kim, Changil [Department of Biotechnology, Konkuk University, Chungju 380-701 (Korea, Republic of); Suh, Yongjoon, E-mail: hiswork@hanmail.net [Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Lee, Su-Jae, E-mail: sj0420@hanyang.ac.kr [Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of)

2015-08-01

Poor prognosis of breast cancer patients is closely associated with metastasis and relapse. There is substantial evidence supporting that cancer stem-like cells (CSCs) are primarily responsible for relapse in breast cancer after anticancer treatment. However, there is a lack of suitable drugs that target breast cancer stem-like cells (BCSCs). Here, we report that phloroglucinol (PG), a natural phlorotannin component of brown algae, suppresses sphere formation, anchorage-independent colony formation and in vivo tumorigenicity. In line with these observations, treatment with PG also decreased CD44{sup +} cancer cell population as well as expression of CSC regulators such as Sox2, CD44, Oct4, Notch2 and β-catenin. Also, treatment with PG sensitized breast cancer cells to anticancer drugs such as cisplatin, etoposide, and taxol as well as to ionizing radiation. Importantly, PG inhibited KRAS and its downstream PI3K/AKT and RAF-1/ERK signaling pathways that regulate the maintenance of CSCs. Taken together, our findings implicate PG as a good candidate to target BCSCs and to prevent the disease relapse. - Highlights: • Phloroglucinol suppresses in vivo tumor formation. • Phloroglucinol sensitizes breast cancer cells to anticancer agents. • Phloroglucinol inhibits breast cancer stem-like cells. • Phloroglucinol inhibits PI3K/AKT and KRAS/RAF/ERK signaling pathways.

Breast scintigraphy today: indications and limitations

International Nuclear Information System (INIS)

Schillaci, Orazio; Buscombe, John R.

2004-01-01

Breast carcinoma is the most common neoplasm found among women in the Western world. Mammography (MM) is the most widely used diagnostic imaging method for screening and diagnosing breast cancer. However, despite technical improvements in recent years, MM has known diagnostic limits; consequently not all breast carcinomas are identified on mammograms, especially if the breast is dense, there is a breast prosthesis or the patient has previously undergone radiation, surgery or biopsy. In addition, the mammographic images of benign and malignant lesions can be similar. Therefore, abnormalities detected on MM frequently result in negative biopsies. Scintimammography (SM) is the functional imaging study of the breast using primarily the radiopharmaceuticals 99m Tc-sestamibi and 99m Tc-tetrofosmin. The main advantage of SM is that its functional basis makes this technique a useful complement to MM. SM resolves some of the main limitations of MM as it is not affected by changes in breast morphology. Several single-site and multi-centre studies have demonstrated that SM has an improved specificity compared with MM, because it is better able to distinguish malignant from benign breast lesions. Interestingly, except in smaller lesions, a higher sensitivity has been recorded for SM than for MM in most of these studies as well. Adjunctive use of SM when MM is equivocal can reduce the number of unnecessary breast biopsies and identify previously unexpected sites of breast cancer. SM appears unaffected by the anatomical changes seen following chemotherapy and radiotherapy, and so this technique can be particularly useful in monitoring the treatment of breast cancer patients, especially when breast-conserving treatment is given. The main limitation to SM has been the sub-optimal resolution of the standard Anger gamma camera, which makes it difficult to detect lesions of less than 10 mm; however, the development of high-resolution breast-dedicated gamma cameras may offer

Breast scintigraphy today: indications and limitations

Energy Technology Data Exchange (ETDEWEB)

Schillaci, Orazio [Department of Biopathology and Diagnostic Imaging, University ' ' Tor Vergata' ' , Rome (Italy); Buscombe, John R. [Department of Nuclear Medicine, Royal Free Hospital, London (United Kingdom)

2004-06-01

Breast carcinoma is the most common neoplasm found among women in the Western world. Mammography (MM) is the most widely used diagnostic imaging method for screening and diagnosing breast cancer. However, despite technical improvements in recent years, MM has known diagnostic limits; consequently not all breast carcinomas are identified on mammograms, especially if the breast is dense, there is a breast prosthesis or the patient has previously undergone radiation, surgery or biopsy. In addition, the mammographic images of benign and malignant lesions can be similar. Therefore, abnormalities detected on MM frequently result in negative biopsies. Scintimammography (SM) is the functional imaging study of the breast using primarily the radiopharmaceuticals {sup 99m}Tc-sestamibi and {sup 99m}Tc-tetrofosmin. The main advantage of SM is that its functional basis makes this technique a useful complement to MM. SM resolves some of the main limitations of MM as it is not affected by changes in breast morphology. Several single-site and multi-centre studies have demonstrated that SM has an improved specificity compared with MM, because it is better able to distinguish malignant from benign breast lesions. Interestingly, except in smaller lesions, a higher sensitivity has been recorded for SM than for MM in most of these studies as well. Adjunctive use of SM when MM is equivocal can reduce the number of unnecessary breast biopsies and identify previously unexpected sites of breast cancer. SM appears unaffected by the anatomical changes seen following chemotherapy and radiotherapy, and so this technique can be particularly useful in monitoring the treatment of breast cancer patients, especially when breast-conserving treatment is given. The main limitation to SM has been the sub-optimal resolution of the standard Anger gamma camera, which makes it difficult to detect lesions of less than 10 mm; however, the development of high-resolution breast-dedicated gamma cameras may offer

Requirements for effective functional breast imaging

International Nuclear Information System (INIS)

Weinberg, I.N.; Zawarzin, V.; Adler, L.P.; Pani, R.; DeVincentis, G.; Khalkhali, I.; Vargas, H.; Venegas, R.; Kim, S.C.; Bakale, G.; Levine, E.; Perrier, N.; Freimanis, R.I.; Lesko, N.M.; Newman, D.P.; Geisinger, K.R.; Berg, W.A.; Masood, S.

2003-01-01

Most nuclear medicine physicists were trained on devices aimed at functional neuroimaging. The clinical goals of brain-centered devices differ dramatically from the parameters needed to be useful in the breast clinic. We will discuss similarities and differences that impact on design considerations, and describe our latest generation of positron emission mammography and intraoperative products. - Source of physiologic contrast: Clinical neuroimaging depends on flow agents to detect the presence of breaks in the blood-brain barrier. Breast flow agents are nonspecific, and may miss preinvasive lesions. - Resolution: Brain cancers are generally diagnosed at late stages, so resolution is not so critical. Detecting early breast cancers, and specifying margins for surgery requires 3 mm spatial resolution or better. - Prevalence: Primary brain cancer is uncommon, and lesions mimicking brain cancer are rare. Primary breast cancer is common, and benign lesions are even more common, so specificity and biopsy capability are very important. - Anatomic references: Brain structure is standard, while breast structure is highly variable, requiring immobilization/compression for physiologic imaging and biopsy. - Surgery: Complete cancer resections for brain are very rare, but are possible for breast with appropriate imaging guidance, implying the need for rapid and reliable imaging. To summarize, the breast clinic needs a rapid and highly sensitive method of assessing breast physiology, compatible with biopsy and surgery. Positron emission mammography devices, in handheld and X-ray platform based configurations, are ideal for this mission

Dietary Natural Products for Prevention and Treatment of Breast Cancer.

Science.gov (United States)

Li, Ya; Li, Sha; Meng, Xiao; Gan, Ren-You; Zhang, Jiao-Jiao; Li, Hua-Bin

2017-07-08

Breast cancer is the most common cancer among females worldwide. Several epidemiological studies suggested the inverse correlation between the intake of vegetables and fruits and the incidence of breast cancer. Substantial experimental studies indicated that many dietary natural products could affect the development and progression of breast cancer, such as soy, pomegranate, mangosteen, citrus fruits, apple, grape, mango, cruciferous vegetables, ginger, garlic, black cumin, edible macro-fungi, and cereals. Their anti-breast cancer effects involve various mechanisms of action, such as downregulating ER-α expression and activity, inhibiting proliferation, migration, metastasis and angiogenesis of breast tumor cells, inducing apoptosis and cell cycle arrest, and sensitizing breast tumor cells to radiotherapy and chemotherapy. This review summarizes the potential role of dietary natural products and their major bioactive components in prevention and treatment of breast cancer, and special attention was paid to the mechanisms of action.

Characterization and cloning of laccase gene from Hericium coralloides NBRC 7716 suitable for production of epitheaflagallin 3-O-gallate.

Science.gov (United States)

Itoh, Nobuya; Takagi, Shinya; Miki, Asami; Kurokawa, Junji

2016-01-01

Epitheaflagallin 3-O-gallate (ETFGg) is a minor polyphenol found in black tea extract, which has good physiological functions. It is synthesized from epigallocatechin gallate (EGCg) with gallic acid via laccase oxidation. Various basidiomycetes and fungi were screened to find a suitable laccase for the production of ETFGg. A basidiomycete, Hericium coralloides NBRC 7716, produced an appropriate extracellular laccase. The purified laccase produced twice the level of ETFGg compared with commercially available laccase from Trametes sp. The enzyme, termed Lcc2, is a monomeric protein with an apparent molecular mass of 67.2 kDa. The N-terminal amino acid sequence of Lcc2 is quite different from laccase isolated from the fruiting bodies of Hericium. Lcc2 showed similar substrate specificity to known laccases and could oxidize various phenolic substrates, including pyrogallol, gallic acid, and 2,6-dimethoxyphenol. The full-length lcc2 gene was obtained by PCR using degenerate primers, which were designed based on the N-terminal amino acid sequence of Lcc2 and conserved copper-binding sites of laccases, and 5'-, and 3'-RACE PCR with mRNA. The Lcc2 gene showed homology with Lentinula edodes laccase (sharing 77% amino acid identity with Lcc6). We successfully produced extracellular Lcc2 using a heterologous expression system with Saccharomyces cerevisiae. Moreover, it was confirmed that the recombinant laccase generates similar levels of ETFGg as the native enzyme. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of a Hanging-Breast PET System for Primary Tumor Visualization in Patients With Stage I-III Breast Cancer: Comparison With Standard PET/CT.

Science.gov (United States)

Teixeira, Suzana C; Rebolleda, José Ferrér; Koolen, Bas B; Wesseling, Jelle; Jurado, Raúl Sánchez; Stokkel, Marcel P M; Del Puig Cózar Santiago, María; van der Noort, Vincent; Rutgers, Emiel J Th; Valdés Olmos, Renato A

2016-06-01

The purposes of this study were to evaluate the performance of a mammography with molecular imaging PET (MAMMI-PET) system for breast imaging in the hanging-breast position for the visualization of primary breast cancer lesions and to compare this method with whole-body PET/CT. Between March 2011 and March 2014, a prospective evaluation included women with one or more histologically confirmed primary breast cancer lesions (index lesions). After injection of 180-240 MBq of (18)F-FDG, whole-body PET/CT and MAMMI-PET acquisitions were performed, index lesions were scored 0, 1, or 2 for FDG uptake relative to background. Detection and FDG uptake were compared by breast length, maximal tumor diameter, affected breast quadrants, tumor grade, and histologic and immunologic sub-types. Finally, the two PET modalities were compared for detection of index lesions. For 234 index lesions (diameter, 5-170 mm), the overall sensitivity was 88.9% for MAMMI-PET and 91% for PET/CT (p = 0.61). Twenty-three (9.8%) index lesions located too close to the pectoral muscle were missed with MAMMI-PET, and 20 index lesions were missed with PET/CT. Lesion visibility on MAMMI-PET images was influenced by tumor grade (p = 0.034) but not by cancer subtype (p = 0.65). Although in an overall evaluation MAMMI-PET was not superior to PET/CT, MAMMI-PET does have higher sensitivity for primary breast cancer lesions within the scanning range of the device. Optimization of the positioning device may increase visualization of the most dorsal lesions.

Hepcidin as a possible marker in determination of malignancy degree and sensitivity of breast cancer cells to cytostatic drugs.

Science.gov (United States)

Yalovenko, T M; Todor, I M; Lukianova, N Y; Chekhun, V F

2016-06-01

To investigate the role of hepcidin (Hepc) in the formation of cells malignant phenotype in vitro and its expression in the dyna-mics of growth of Walker-256 carcinosarcoma with different sensitivity to doxorubicin (Dox). The cell lines used in the analysis included T47D, MCF-7, MDA-MB-231, MDA-MB-468, MCF/CP, and MCF/Dox. Hepc expression was studied by immunocytochemical method. "Free" iron content was determined by EPR spectroscopy. Determination of Hepc expression in homogenates of tumor tissue and in blood serum of rats with Dox-sensitive and -resistant Walker-256 carcinosarcoma was performed. It was found that Hepc levels in breast cancer (BC) cells with high degree of malignancy (MDA-MB-231, MDA-MB-468) and drug-resistant phenotype (MCF/CP, MCF/Dox) were by 1.5-2 times higher (p < 0.05) in comparison with sensitive and less malignant BC cells. The development of drug-resistant phenotype in Walker-256 carcinosarcoma cells was accompanied by increasing of Hepc and "free" iron content (by 2.4 and 1.2 times, respectively). The data of in vitro and in vivo research evidenced on involvement of Hepc in formation of BC cells malignant phenotype and their resistance to Dox.

Structural phase transition in lanthanum gallate as studied by Raman and X-ray diffraction measurements

Energy Technology Data Exchange (ETDEWEB)

Dhak, P.; Pramanik, P. [Department of Chemistry, Indian Institute of Technology, Kharagpur 721302 (India); Bhattacharya, S.; Roy, Anushree [Department of Physics, Indian Institute of Technology, Kharagpur 721302 (India); Achary, S.N.; Tyagi, A.K. [Chemistry Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)

2011-08-15

Lanthanum gallate (LaGaO{sub 3}) is known to undergo orthorhombic to rhombohedral first order phase transition at 150 C. In this article we have shown that by introducing 2% La deficiency in the system, coexistence of above two phases can be obtained at lower temperature and a complete phase transition occurs at 200 C. The evolution of structural parameters of the system with temperature is reported from X-ray diffraction measurements and Rietveld analysis of the diffraction patterns. The change in local octahedral distortion due to 2% La deficiency is revealed through the shift in the phonon modes of GaO{sub 6} octahedra, in both orthorhombic and rhombohedral phase. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Clarifying the debate on population-based screening for breast cancer with mammography

Science.gov (United States)

Chen, Tony Hsiu-Hsi; Yen, Amy Ming-Fang; Fann, Jean Ching-Yuan; Gordon, Paula; Chen, Sam Li-Sheng; Chiu, Sherry Yueh-Hsia; Hsu, Chen-Yang; Chang, King-Jen; Lee, Won-Chul; Yeoh, Khay Guan; Saito, Hiroshi; Promthet, Supannee; Hamashima, Chisato; Maidin, Alimin; Robinson, Fredie; Zhao, Li-Zhong

2017-01-01

Abstract Background: The recent controversy about using mammography to screen for breast cancer based on randomized controlled trials over 3 decades in Western countries has not only eclipsed the paradigm of evidence-based medicine, but also puts health decision-makers in countries where breast cancer screening is still being considered in a dilemma to adopt or abandon such a well-established screening modality. Methods: We reanalyzed the empirical data from the Health Insurance Plan trial in 1963 to the UK age trial in 1991 and their follow-up data published until 2015. We first performed Bayesian conjugated meta-analyses on the heterogeneity of attendance rate, sensitivity, and over-detection and their impacts on advanced stage breast cancer and death from breast cancer across trials using Bayesian Poisson fixed- and random-effect regression model. Bayesian meta-analysis of causal model was then developed to assess a cascade of causal relationships regarding the impact of both attendance and sensitivity on 2 main outcomes. Results: The causes of heterogeneity responsible for the disparities across the trials were clearly manifested in 3 components. The attendance rate ranged from 61.3% to 90.4%. The sensitivity estimates show substantial variation from 57.26% to 87.97% but improved with time from 64% in 1963 to 82% in 1980 when Bayesian conjugated meta-analysis was conducted in chronological order. The percentage of over-detection shows a wide range from 0% to 28%, adjusting for long lead-time. The impacts of the attendance rate and sensitivity on the 2 main outcomes were statistically significant. Causal inference made by linking these causal relationships with emphasis on the heterogeneity of the attendance rate and sensitivity accounted for the variation in the reduction of advanced breast cancer (none-30%) and of mortality (none-31%). We estimated a 33% (95% CI: 24–42%) and 13% (95% CI: 6–20%) breast cancer mortality reduction for the best scenario (90

Breast-specific gamma-imaging: molecular imaging of the breast using 99mTc-sestamibi and a small-field-of-view gamma-camera.

Science.gov (United States)

Jones, Elizabeth A; Phan, Trinh D; Blanchard, Deborah A; Miley, Abbe

2009-12-01

Breast-specific gamma-imaging (BSGI), also known as molecular breast imaging, is breast scintigraphy using a small-field-of-view gamma-camera and (99m)Tc-sestamibi. There are many different types of breast cancer, and many have characteristics making them challenging to detect by mammography and ultrasound. BSGI is a cost-effective, highly sensitive and specific technique that complements other imaging modalities currently being used to identify malignant lesions in the breast. Using the current Society of Nuclear Medicine guidelines for breast scintigraphy, Legacy Good Samaritan Hospital began conducting BSGI, breast scintigraphy with a breast-optimized gamma-camera. In our experience, optimal imaging has been conducted in the Breast Center by a nuclear medicine technologist. In addition, the breast radiologists read the BSGI images in correlation with the mammograms, ultrasounds, and other imaging studies performed. By modifying the current Society of Nuclear Medicine protocol to adapt it to the practice of breast scintigraphy with these new systems and by providing image interpretation in conjunction with the other breast imaging studies, our center has found BSGI to be a valuable adjunctive procedure in the diagnosis of breast cancer. The development of a small-field-of-view gamma-camera, designed to optimize breast imaging, has resulted in improved detection capabilities, particularly for lesions less than 1 cm. Our experience with this procedure has proven to aid in the clinical work-up of many of our breast patients. After reading this article, the reader should understand the history of breast scintigraphy, the pharmaceutical used, patient preparation and positioning, imaging protocol guidelines, clinical indications, and the role of breast scintigraphy in breast cancer diagnosis.

Data in support of the negative influence of divalent cations on (?)-epigallocatechin-3-gallate (EGCG)-mediated inhibition of matrix metalloproteinase-2 (MMP-2)

OpenAIRE

Deb, Gauri; Batra, Sahil; Limaye, Anil M.

2015-01-01

In this data article we have provided evidence for the negative influence of divalent cations on (−)‐epigallocatechin-3-gallate (EGCG)-mediated inhibition of matrix metalloproteinase-2 (MMP-2) activity in cell-free experiments. Chelating agents, such as EDTA and sodium citrate alone, did not affect MMP-2 activity. While EDTA enhanced, excess of divalent cations interfered with EGCG-mediated inhibition of MMP-2.

Epigallocatechin gallate (EGCG), a major component of green tea, is a dual phosphoinositide-3-kinase/mTOR inhibitor

International Nuclear Information System (INIS)

Van Aller, Glenn S.; Carson, Jeff D.; Tang, Wei; Peng, Hao; Zhao, Lin; Copeland, Robert A.; Tummino, Peter J.; Luo, Lusong

2011-01-01

Research highlights: → Epigallocatechin-3-gallate (EGCG) is an ATP-competitive inhibitor of PI3K and mTOR with Ki values around 300 nM. → EGCG inhibits cell proliferation and AKT phosphorylation at Ser473 in MDA-MB-231and A549 cells. → Molecular docking studies show that EGCG binds well to the PI3K kinase domain active site. → These results suggest another important molecular mechanism for the anticancer activities of EGCG. -- Abstract: The PI3K signaling pathway is activated in a broad spectrum of human cancers, either directly by genetic mutation or indirectly via activation of receptor tyrosine kinases or inactivation of the PTEN tumor suppressor. The key nodes of this pathway have emerged as important therapeutic targets for the treatment of cancer. In this study, we show that (-)-epigallocatechin-3-gallate (EGCG), a major component of green tea, is an ATP-competitive inhibitor of both phosphoinositide-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) with K i values of 380 and 320 nM respectively. The potency of EGCG against PI3K and mTOR is within physiologically relevant concentrations. In addition, EGCG inhibits cell proliferation and AKT phosphorylation at Ser473 in MDA-MB-231 and A549 cells. Molecular docking studies show that EGCG binds well to the PI3K kinase domain active site, agreeing with the finding that EGCG competes for ATP binding. Our results suggest another important molecular mechanism for the anticancer activities of EGCG.

The usefulness of mammography and scintimammography in differential diagnosis of breast tumor

International Nuclear Information System (INIS)

Kang, Bong Joo; Chung, Young An; Jung, Hyun Seok; Jung, Jung Im; Yoo, Ie Ryung; Kim, Sung Hoon; Sohn, Hyung Sun; Chung, Soo Kyo; Hahn, Seong Tai; Lee, Jae Mun

2004-01-01

lt is very important to differentiate breast cancer from benign mass. There are many reports to evaluate the differential diagnosis under the several diagnostic tools. We evaluated the usefulness of mammography and Tc-99m MIBI scintimammography in the differential diagnosis of breast mass and correlated with pathologic findings. This study included 80 patients (age: 24-72, mean: 48.4) who underwent mammography and Tc-99m MlBI scintimammography for breast masses. Scintimammographies (anterior-posterior and lateral projections) were acquired in 10 minutes and 2 hours after intravenous injection of Tc-99m MlBl. Four specialists in diagnostic radiology and nuclear medicine evaluated the findings of breast masses under the mammography and Tc-99m MIBI scintimammography, and calculated the tumor to background (T/B) ratio. The pathologic results were obtained and we statistically analyzed the correlations between pathologic results and imaging findings under the mammography and Tc-99m MIBI scintimammography by chi-square and correlation test. The sensitivity, specificity, positive predictive value, and negative predictive value of mammography for detection of breast cancer were 87.5%, 56.3%, 75.0%, and 75.0% respectively. 45 cases of 80 patients were suspicious for breast cancer under the Tc-99m MIBI scintimammography. 41 cases of 45 patients were confirmed as breast cancer and the remaining 4 cases were confirmed as benign masses. The sensitivity, specificity, positive predictive value and negative predictive value of Tc-99m MIBI scintimammography for detection of breast cancer were 85.4%, 87.5%, 91.1%, and 80.8% respectively. The sensitivity of scintimammography was lower than that of mammography for detection of breast cancer, however the specificity, positive predictive value, and negative predictive value were higher. In the benign mass, the mean T/B ratio in 10 minutes was 1.409±0.30, and that in 2 hours was 1.267±0.42. The maximal T/B ratio of benign mass in 10

Radiation sensitivity and EPR dosimetric potential of gallic acid and its esters

Science.gov (United States)

Tuner, Hasan; Oktay Bal, M.; Polat, Mustafa

2015-02-01

In the preset work the radiation sensitivities of Gallic Acid anhydrous and monohydrate, Octyl, Lauryl, and Ethyl Gallate (GA, GAm, OG, LG, and EG) were investigated in the intermediate (0.5-20 kGy) and low radiation (<10 Gy) dose range using Electron Paramagnetic Resonance (EPR) spectroscopy. While OG, LG, and EG are presented a singlet EPR spectra, their radiation sensitivity found to be very different in the intermediate dose range. At low radiation dose range (<10 Gy) only LG is found to be present a signal that easily distinguished from the noise signals. The intermediate and low dose range radiation sensitivities are compared using well known EPR dosimeter alanine. The radiation yields (G) of the interested material were found to be 1.34×10-2, 1.48×10-2, 4.14×10-2, and 6.03×10-2, 9.44×10-2 for EG, GA, GAm, OG, and LG, respectively at the intermediate dose range. It is found that the simple EPR spectra and the noticeable EPR signal of LG make it a promising dosimetric material to be used below 10 Gy of radiation dose.

Stability of Polyphenols Epigallocatechin Gallate and Pentagalloyl Glucose in a Simulated Digestive System

Science.gov (United States)

Krook, Melanie A.; Hagerman, Ann E.

2012-01-01

Polyphenols found in foods and beverages are under intense scrutiny for their potential beneficial effects on human health. We examined the stability of two bioactive polyphenols, epigallocatechin-O-gallate (EGCg) and 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG), in a model digestive system at low oxygen tension with and without added digestive components and foods. Both compounds were stable at pH values of 5–6 and below, indicating gastric stability. Both compounds decomposed at pH 7.0. PGG was stabilized in a model system containing pepsin, pancreatin, bile and lipase, and/or baby food, but was not stabilized by dry cereal. EGCg was not stabilized by the addition of any biomolecule. The effects of polyphenols on human health should be evaluated in the context of their stability in the digestive tract with and without added digestive components and/or food. PMID:23028206

In vitro activity of 23 tea extractions and epigallocatechin gallate against Candida species

DEFF Research Database (Denmark)

Chen, Ming; Zhai, Lin; Arendrup, Maiken Cavling

2015-01-01

In this study, we investigate the susceptibility of Candida albicans, Candida glabrata, Candida krusei, Candida parapsilosis, Candida tropicalis, and Aspergillus fumigatus using the EUCAST microdilution minimum inhibitory concentration (MIC) method (final tea supernatant concentration range 5.......0-0.005 mg/ml) to 23 different teas and tea catechins including epigallocatechin gallate (EGCG) isolated from green tea. All teas exhibited potent in vitro antifungal activity against C. glabrata. Six out of nine green teas and three of eight black teas had an MIC of 0.078 mg/ml, one white tea had an MIC...... of 0.156 mg/ml, and finally three of five oolong teas had an MIC of 0.156 mg/ml. Three teas exhibited activity against C. albicans (MIC 1.25 mg/ml), one green tea was active against C. parapsilosis (MIC 1.25 mg/ml), but none were effective against C. krusei, C. tropicalis or A. fumigatus...

Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results

Science.gov (United States)

Bigio, Irving J.; Brown, Stephen G.; Briggs, Gavin M.; Kelley, Christine; Lakhani, Sunil; Pickard, David; Ripley, Paul M.; Rose, Ian; Saunders, Christobel

2000-04-01

We report on the first stages of a clinical study designed to test elastic-scattering spectroscopy, medicated by fiberoptic probes, for three specific clinical applications in breast-tissue diagnosis: (1) a transdermal-needle (interstitial) measurement for instant diagnosis with minimal invasiveness similar to fine-needle aspiration but with sensitivity to a larger tissue volume, (2) a hand-held diagnostic probe for use in assessing tumor/resection margins during open surgery, and (3) use of the same probe for real-time assessment of the `sentinel' node during surgery to determine the presence or absence of tumor (metastatic). Preliminary results from in vivo measurements on 31 women are encouraging. Optical spectra were measured on 72 histology sites in breast tissue, and 54 histology sites in sentinel nodes. Two different artificial intelligence methods of spectral classification were studied. Artificial neural networks yielded sensitivities of 69% and 58%, and specificities of 85% and 93%, for breast tissue and sentinel nodes, respectively. Hierarchical cluster analysis yielded sensitivities of 67% and 91%, and specificities of 79% and 77%, for breast tissue and sentinel nodes, respectively. These values are expected to improve as the data sets continue to grow and more sophisticated data preprocessing is employed. The study will enroll up to 400 patients over the next two years.

Relation between Mammographic Parenchymal Patterns and Breast Cancer Risk: Considering BMI, Compressed Breast Thickness and Age of Women in Tabriz, Iran.

Science.gov (United States)

Mehnati, Parinaz; Alizadeh, Hamed; Hoda, Haleh

2016-01-01

Mammographic density determined according paranchymal patterns is a risk factor for breast cancer and its relationships with body and other breast characteristics of women is important. The purpose of the present study was to correlate breast parenchymal patterns and mammography abnormality findings with women's BMI, compressed breast thickness (CBT) and age in Tabriz city, Iran. From 1,100 mammograms interpreted by radiologists, breast parenchymal was classified into four categories from Types 1 (mostly fatty) through 4 (mostly fibroglandular tissue). Age, BMI, and CBT were recorded and their relation with risk for the development of breast abnormalities in mammograms was analyzed. In women with a mean age of 45.8±8.63 years 17.7% were in the high density group (Type 3 and 4). A comparison of four types of breast paranchymal with BMI, CBT and age showed inverse relations to breast density. Abnormal mammographic findings were 25.8% of all reported mammograms with a circular mass (12.7%) as the most common abnormality. About 21% abnormal cases were in less than 40 years. Increasing of BMI had significant relation with breast abnormality but in CBT was not observed. Measurement of women's body characteristics is useful for assistance in mammography diagnosis as well as selection of imaging instrument by high sensitivity for following patient in future. The effects of age, CBT and BMI groups on the breast paranchymal were significant.

Comparative study of diffusion weighted imaging and dynamic contrast enhanced MRI for the detection of small breast cancers

International Nuclear Information System (INIS)

Tang Jianhua; Yan Fuhua; Zhou Meiling; Ye Fang; Xu Pengju

2008-01-01

Objective: To compare the sensitivity of diffusion weighted imaging (DWI) with dynamic contrast enhanced (DCE) MRI for the detection of small breast cancers and to evaluate the clinical value of DWI. Methods: Forty-eight patients with benign (n=25) and malignant (n=45) small breast lesions (≤2 cm) proved by pathology underwent DWI and DCE MRI. The DCE MRI was performed using FLASH sequence and the time-signal intensity curve was drawn. The DWI was performed using GRAPPA- EPI sequence with different b values (800, 1000 s/mm 2 ) and the ADC values of lesions were measured. The sensitivity and specificity of DWI for the detection of small breast cancers were compared with DCE MRI. Results: Forty of 45 small breast cancers and 19 of 25 small benign breast lesions were correctly diagnosed using DCE MRI. The sensitivity and positive predictive value of TIC were 88.9% (40/45) and 87.0% (40/46). With b values of 800 s/mm 2 and 1000 s/mm 2 , the average ADC values of small breast cancers were (1.153±0.192) x 10 -3 and (1.079±0.186) x 10 -3 mm 2 /s, while those of benign ones were (1.473±0.252) x 10 -3 and (1.419 ± 0.255) x 10 -3 mm 2 /s, respectively. There was no significant difference for the ADC values with different b values in the same group (P>0.05), while there was a significant difference between the malignant and the benign lesions (P 2 . Both the sensitivity and positive predictive value of diagnosis were 86.7% (39/45). The abilities of DWI and DCE MRI for the diagnosis of small breast cancers were the same. The sensitivity (93.3%) and positive predictive value (91.3%) were improved with the combination of DCE MRI and DWI. Conclusion: DWI has a high sensitivity for the detection of small breast cancers, the ADC value can provide valuable information in the differential diagnosis. (authors)

FDG-PET/CT in the diagnosis of recurrent breast cancer

International Nuclear Information System (INIS)

Murakami, Ryusuke; Kumita, Shin-ichiro; Yoshida, Tamiko; Ishihara, Keiichi; Kiriyama, Tomonari; Hakozaki, Kenta; Yanagihara, Keiko; Lida, Shinya; Tsuchiya, Shin-ichi

2012-01-01

Background. An advantage of PET/CT has been demonstrated for diagnosis of several tumor entities. In patients with breast cancer, early diagnosis and accurate restaging of recurrence after surgery is important for selection of the most appropriate therapeutic strategy. Purpose. To evaluate the accuracy of integrated positron emission tomography and computed tomography (PET/CT) using 18F-fluorodeoxyglucose (FDG), for follow-up of patients with suspected recurrent breast cancer. Material and Methods. Forty-seven patients with suspected recurrent breast cancer underwent PET/CT. The PET and PET/CT images were interpreted without knowledge of the results of other diagnostic modalities, and compared with each other with reference to the final diagnosis. Results. Twenty-five (53%) patients suffered tumor recurrence. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT were 96%, 91%, 92%, 95%, and 94%, respectively. In comparison with PET, PET/CT had a higher sensitivity and accuracy (96% vs. 80% and 94% vs. 81%, respectively). The difference in diagnostic accuracy between PET/CT and PET was significant (P < 0.05). Conclusion. The present findings indicate that PET/CT is an accurate, sensitive and reliable modality for screening and detection of breast cancer recurrence. PET/CT appears to be an effective surveillance tool, as it is able to cover the whole body in a single procedure and shows good performance

Nuclear medicine in breast cancer diagnostics: Primary tumor and lymphatic metastasis

Science.gov (United States)

Sinilkin, I.; Medvedeva, A.; Chernov, V.; Slonimskaya, E.; Zelchan, R.; Bragina, O.

2017-09-01

The purpose of the study: to assess the possibility of using nuclear medicine techniques at the stages of diagnosis and treatment of breast cancer. Materials and Methods: The study included 290 patients with breast cancer and 70 patients with benign breast tumors. The study was used as a radiopharmaceutical 99mTc-MIBI, 199Tl for imaging tumors and colloid 99mTc-Aloteh for visualization sentinel lymph nodes (SLN), colloid was injected peritumoral in four points to 80 MBq one day prior to the planned operation. Results: The sensitivity of SPECT using both 99mTc-MIBI and 199Tl for breast cancer detection was shown to be rather high, being 98.5% and 98%, respectively. It should be noted that the sensitivity of SPECT in detection of small tumors (less than 1 cm in diameter) and multicentric tumors was not high irrespective of the radioisotope used (60% and 65% with 99mTc-MIBI and 65% and 59% with 199Tl, respectively). The difference in the sensitivity was found between 99mTc-MIBI and 199T for the detection of regional lymph node metastasis (91% vs 70%). SLN were detected in 31 patients. The most commonly SLN were defined in the axillary region of 96.7%. In 22 (70.9%) patients there was no metastasis SLN. The sensitivity of the method was 91.2%, specificity of 100%. Conclusion: The specificity of SPECT with 199Tl was higher than that with 99mTc-MIBI. The data obtained show that SPECT with 199Tl can be recommended for its use as an additional breast cancer detection method in cases when other imaging techniques and histological findings are not accurate enough. The clinical study of 99mTc-Aloteh, a new radiopharmaceutical agent, has shown that the studied colloid has high uptake level in SLN and can be successfully used for visualization of SLN in patients with breast cancer.

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

International Nuclear Information System (INIS)

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

2013-01-01

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 (I 1 /I 2 %)) 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 I 1 /I 2 %=44.9±11.0 and 52.4±7.6 for malignant and benign samples respectively. - Highlights: • X-ray scattering profiles of breast tissue samples are acquired. • Three X-ray profile characterization parameters are calculated. • The cut-offs, sensitivity, specificity and diagnostic accuracy are calculated. • They are compared to the data from non-lyophilized samples. • Results show increased sensitivity in case of lyophilized samples

Comparative evaluation of average glandular dose and breast cancer detection between single-view digital breast tomosynthesis (DBT) plus single-view digital mammography (DM) and two-view DM: correlation with breast thickness and density

International Nuclear Information System (INIS)

Shin, Sung Ui; Chang, Jung Min; Bae, Min Sun; Lee, Su Hyun; Cho, Nariya; Seo, Mirinae; Kim, Won Hwa; Moon, Woo Kyung

2015-01-01

To compare the average glandular dose (AGD) and diagnostic performance of mediolateral oblique (MLO) digital breast tomosynthesis (DBT) plus cranio-caudal (CC) digital mammography (DM) with two-view DM, and to evaluate the correlation of AGD with breast thickness and density. MLO and CC DM and DBT images of both breasts were obtained in 149 subjects. AGDs of DBT and DM per exposure were recorded, and their correlation with breast thickness and density were evaluated. Paired data of MLO DBT plus CC DM and two-view DM were reviewed for presence of malignancy in a jack-knife alternative free-response ROC (JAFROC) method. The AGDs of both DBT and DM, and differences in AGD between DBT and DM (ΔAGD), were correlated with breast thickness and density. The average JAFROC figure of merit (FOM) was significantly higher on the combined technique than two-view DM (P = 0.005). In dense breasts, the FOM and sensitivity of the combined technique was higher than that of two-view DM (P = 0.003) with small ΔAGD. MLO DBT plus CC DM provided higher diagnostic performance than two-view DM in dense breasts with a small increase in AGD. (orig.)

Comparative evaluation of average glandular dose and breast cancer detection between single-view digital breast tomosynthesis (DBT) plus single-view digital mammography (DM) and two-view DM: correlation with breast thickness and density

Energy Technology Data Exchange (ETDEWEB)

Shin, Sung Ui; Chang, Jung Min; Bae, Min Sun; Lee, Su Hyun; Cho, Nariya; Seo, Mirinae; Kim, Won Hwa; Moon, Woo Kyung [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of)

2015-01-15

To compare the average glandular dose (AGD) and diagnostic performance of mediolateral oblique (MLO) digital breast tomosynthesis (DBT) plus cranio-caudal (CC) digital mammography (DM) with two-view DM, and to evaluate the correlation of AGD with breast thickness and density. MLO and CC DM and DBT images of both breasts were obtained in 149 subjects. AGDs of DBT and DM per exposure were recorded, and their correlation with breast thickness and density were evaluated. Paired data of MLO DBT plus CC DM and two-view DM were reviewed for presence of malignancy in a jack-knife alternative free-response ROC (JAFROC) method. The AGDs of both DBT and DM, and differences in AGD between DBT and DM (ΔAGD), were correlated with breast thickness and density. The average JAFROC figure of merit (FOM) was significantly higher on the combined technique than two-view DM (P = 0.005). In dense breasts, the FOM and sensitivity of the combined technique was higher than that of two-view DM (P = 0.003) with small ΔAGD. MLO DBT plus CC DM provided higher diagnostic performance than two-view DM in dense breasts with a small increase in AGD. (orig.)

Value of breast MRI as supplement to mammography and sonography for high risk breast cancer patients; Wertigkeit der Mamma-MRT als Ergaenzung zu Mammographie und Sonographie bei Patientinnen mit erhoehtem Mammakarzinomrisiko

Energy Technology Data Exchange (ETDEWEB)

Schlossbauer, T.; Hellerhoff, K.; Reiser, M. [Klinikum Grosshadern der Ludwig-Maximilians-Universitaet Muenchen, Institut fuer Klinische Radiologie, Muenchen (Germany)

2008-04-15

The aim of this study is to give an overview on early detection of breast cancer in patients with an increased risk of breast cancer. Sensitivities and diagnostic accuracies of breast MRI, mammography and ultrasound were compared. A systematic literature search of the past 3 years was performed. Studies which compared breast imaging modalities and used image-guided biopsy results as standard of reference were included. Patients included had to have had an increased lifetime risk for breast cancer (>15%). Regarding sensitivity and diagnostic accuracy, breast MRI performed best in comparison to the other modalities within this collective of patients. Sensitivities ranged from 71-100%, 0-78%, and 13-65%, for MRI, mammography, and ultrasound, respectively Breast MRI is a well established tool for screening in patients at high risk for developing breast cancer and is a valuable supplement to mammography and ultrasound within this selected cohort of patients. (orig.) [German] Ziele der Arbeit sind die inhaltliche Einfuehrung in das Thema Frueherkennung des Mammakarzinoms bei Patientinnen mit erhoehtem Risiko und eine systematische Analyse der Wertigkeit von MRT und anderen bildgebenden Verfahren in diesem Zusammenhang. Es wurde eine systematische Literaturrecherche ueber die letzten 3 Jahre durchgefuehrt. Dabei wurden Vergleichsstudien der verschiedenen bildgebenden Verfahren in der Mammadiagnostik beruecksichtigt, bei denen die bildgesteuerte Biopsie als Goldstandard angegeben wurde. Von allen bildgebenden Verfahren zeigt die Mamma-MRT bei Patientinnen mit familiaerem Risiko die hoechste Sensitivitaet und diagnostische Genauigkeit bei der Detektion des Mammakarzinoms. Fuer MRT, Mammographie und Sonographie werden Sensitivitaeten zwischen 71 und 100%, 0 und 78% sowie 13 und 65% angegeben. Die Mamma-MRT ist ein etabliertes Verfahren zum Screening von Risikopatientinnen. Uebereinstimmend wird der diagnostische Nutzen der Mamma-MRT als ergaenzendes Verfahren zu Mammographie

High resolution PET breast imager with improved detection efficiency

Science.gov (United States)

Majewski, Stanislaw

2010-06-08

A highly efficient PET breast imager for detecting lesions in the entire breast including those located close to the patient's chest wall. The breast imager includes a ring of imaging modules surrounding the imaged breast. Each imaging module includes a slant imaging light guide inserted between a gamma radiation sensor and a photodetector. The slant light guide permits the gamma radiation sensors to be placed in close proximity to the skin of the chest wall thereby extending the sensitive region of the imager to the base of the breast. Several types of photodetectors are proposed for use in the detector modules, with compact silicon photomultipliers as the preferred choice, due to its high compactness. The geometry of the detector heads and the arrangement of the detector ring significantly reduce dead regions thereby improving detection efficiency for lesions located close to the chest wall.

Breast cancer after radiotherapy for skin hemangioma in infancy

International Nuclear Information System (INIS)

Lundell, M.; Mattsson, A.; Hakulinen, T.; Holm, L.E.

1996-01-01

Between 1920 and 1959, 9675 women were irradiated in infancy for skin hemangioma at Radiumhemmet, Stockholm. They were exposed to low to moderate doses of ionizing radiation. The mean age at first exposure was 6 months and the mean absorbed dose to the breast anlage was 0.39 Gy (range 50 years after exposure the ERR at 1 Gy was 2.25 (95% CI 0.59-5.62). The fitted excess absolute risk (EAR) was 22.9 per 10 4 breast-year gray. The breast absorbed dose and time after exposure were important risk determinants for breast cancer excess risk. Forty to 50 years of follow-up was necessary for the excess risk to be expressed. The study confirms previous findings that the breast anlage of female infants is sensitive to ionizing radiation. 17 refs., 6 figs

Usefulness of mammography in the diagnosis and management of breast disease in postmenopausal women

Energy Technology Data Exchange (ETDEWEB)

Lamas, A.M.; Horwitz, R.I.; Peck, D.

1984-12-07

The clinical usefulness of mammography in postmenopausal women was evaluated by conducting a ''vertical'' analysis using indexes of sensitivity and specificity, and a separate ''horizontal'' analysis assessing the relationship between the mammographic test result and the occurrence of specific clinical management decisions. The patients included 105 women with breast cancer, 104 women with fibrocystic breast disease, and 103 women with clinically benign breasts. The study confirmed the generally accepted high values reported for the sensitivity and for the specificity of mammography as a test for breast cancer, while also helping to reconcile the widely varying indexes of test efficacy reported in some studies. The authors also observed that physicians' management decisions vary according to the mammographic interpretation, and include such distinctive clinical strategies as watchful expectancy (observe and follow), repeated mammograms, or breast biopsy. Future studies will need to determine reasons for specific management decisions, especially when they appear to contradict authoritative recommendations.

Usefulness of mammography in the diagnosis and management of breast disease in postmenopausal women

International Nuclear Information System (INIS)

Lamas, A.M.; Horwitz, R.I.; Peck, D.

1984-01-01

The clinical usefulness of mammography in postmenopausal women was evaluated by conducting a ''vertical'' analysis using indexes of sensitivity and specificity, and a separate ''horizontal'' analysis assessing the relationship between the mammographic test result and the occurrence of specific clinical management decisions. The patients included 105 women with breast cancer, 104 women with fibrocystic breast disease, and 103 women with clinically benign breasts. The study confirmed the generally accepted high values reported for the sensitivity and for the specificity of mammography as a test for breast cancer, while also helping to reconcile the widely varying indexes of test efficacy reported in some studies. The authors also observed that physicians' management decisions vary according to the mammographic interpretation, and include such distinctive clinical strategies as watchful expectancy (observe and follow), repeated mammograms, or breast biopsy. Future studies will need to determine reasons for specific management decisions, especially when they appear to contradict authoritative recommendations

A treatment planning study comparing whole breast radiation therapy against conformal, IMRT and tomotherapy for accelerated partial breast irradiation

International Nuclear Information System (INIS)

Oliver, Mike; Chen, Jeff; Wong, Eugene; Van Dyk, Jake; Perera, Francisco

2007-01-01

Purpose and background: Conventional early breast cancer treatment consists of a lumpectomy followed by whole breast radiation therapy. Accelerated partial breast irradiation (APBI) is an investigational approach to post-lumpectomy radiation for early breast cancer. The purpose of this study is to compare four external beam APBI techniques, including tomotherapy, with conventional whole breast irradiation for their radiation conformity index, dose homogeneity index, and dose to organs at risk. Methods and materials: Small-field tangents, three-dimensional conformal radiation therapy, intensity-modulated radiation therapy and helical tomotherapy were compared for each of 15 patients (7 right, 8 left). One radiation conformity and two dose homogeneity indices were used to evaluate the dose to the target. The mean dose to organs at risk was also evaluated. Results: All proposed APBI techniques improved the conformity index significantly over whole breast tangents while maintaining dose homogeneity and without a significant increase in dose to organs at risk. Conclusion: The four-field IMRT plan produced the best dosimetric results; however this technique would require appropriate respiratory motion management. An alternative would be to use a four-field conformal technique that is less sensitive to the effects of respiratory motion

ATM induction insufficiency in a radiosensitive breast-cancer patient

International Nuclear Information System (INIS)

Clarke, R.A.; Fang, Z.H.; Marr, P.J.; Kearsley, J.H.; Papadatos, G.; Lee, C.S.; University of Sydney, Camperdown, NSW

2002-01-01

ATM induction insufficiency in a radiosensitive breast-cancer patient The ataxia telangiectasia (A-T) gene (ATM) is a dominant breast cancer gene with tumour suppressor activity. ATM also regulates cellular sensitivity to ionising radiation (IR) presumably through its role as a facilitator of DNA repair. In normal cells and tissues the ATM protein is rapidly induced by IR to threshold/maximum levels. The kinase function of the ATM protein is also rapidly activated in response to IR. The fact that women carriers of ATM mutations can have an increased risk of developing breast cancer and that many sporadic breast tumours have reduced levels of the ATM protein broadens the scope of ATM's tumour suppressor within the breast. This report describes the downregulation of ATM protein levels in a radiosensitive breast cancer patient. Postinduction ATM levels were up to tenfold lower in the patient's fresh tissues compared to normal controls. These results might indicate a much broader role for ATM anomalies in breast cancer aetiology. Copyright (2002) Blackwell Science Pty Ltd

Rapid point-of-care breath test for biomarkers of breast cancer and abnormal mammograms.

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Michael Phillips

Full Text Available BACKGROUND: Previous studies have reported volatile organic compounds (VOCs in breath as biomarkers of breast cancer and abnormal mammograms, apparently resulting from increased oxidative stress and cytochrome p450 induction. We evaluated a six-minute point-of-care breath test for VOC biomarkers in women screened for breast cancer at centers in the USA and the Netherlands. METHODS: 244 women had a screening mammogram (93/37 normal/abnormal or a breast biopsy (cancer/no cancer 35/79. A mobile point-of-care system collected and concentrated breath and air VOCs for analysis with gas chromatography and surface acoustic wave detection. Chromatograms were segmented into a time series of alveolar gradients (breath minus room air. Segmental alveolar gradients were ranked as candidate biomarkers by C-statistic value (area under curve [AUC] of receiver operating characteristic [ROC] curve. Multivariate predictive algorithms were constructed employing significant biomarkers identified with multiple Monte Carlo simulations and cross validated with a leave-one-out (LOO procedure. RESULTS: Performance of breath biomarker algorithms was determined in three groups: breast cancer on biopsy versus normal screening mammograms (81.8% sensitivity, 70.0% specificity, accuracy 79% (73% on LOO [C-statistic value], negative predictive value 99.9%; normal versus abnormal screening mammograms (86.5% sensitivity, 66.7% specificity, accuracy 83%, 62% on LOO; and cancer versus no cancer on breast biopsy (75.8% sensitivity, 74.0% specificity, accuracy 78%, 67% on LOO. CONCLUSIONS: A pilot study of a six-minute point-of-care breath test for volatile biomarkers accurately identified women with breast cancer and with abnormal mammograms. Breath testing could potentially reduce the number of needless mammograms without loss of diagnostic sensitivity.

Breast Density Legislation in New England: A Survey Study of Practicing Radiologists.

Science.gov (United States)

Lourenco, Ana P; DiFlorio-Alexander, Roberta M; Slanetz, Priscilla J

2017-10-01

This study aimed to assess radiologists' knowledge about breast density legislation as well as perceived practice changes resulting from the enactment of breast density legislation. This is an institutional review board-exempt anonymous email survey of 523 members of the New England Roentgen Ray Society. In addition to radiologist demographics, survey questions addressed radiologist knowledge of breast density legislation, knowledge of breast density as a risk factor for breast cancer, recommendations for supplemental screening, and perceived practice changes resulting from density notification legislation. Of the 523 members, 96 responded, yielding an 18% response rate. Seventy-three percent of respondents practiced in a state with breast density legislation. Sixty-nine percent felt that breast density notification increased patient anxiety about breast cancer, but also increased patient (74%) and provider (66%) understanding of the effect of breast density on mammographic sensitivity. Radiologist knowledge of the relative risk of breast cancer when comparing breasts of different density was variable. Considerable confusion and controversy regarding breast density persists, even among practicing radiologists. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

The effect of silicone implants on the diagnosis, prognosis, and treatment of breast cancer.

Science.gov (United States)

Handel, Neal

2007-12-01

Because of the prevalence of breast cancer, many augmented women eventually will develop the disease. This article reviews what is known about the effect of implants on the detection, prognosis, and treatment of carcinoma of the breast. Observations were made on 4082 breast cancer patients (3953 nonaugmented and 129 augmented) treated over a 23-year time span. Findings in the two groups were compared and differences analyzed statistically. Mammograms of all women with palpable lesions were reviewed to assess mammographic sensitivity in patients with and without implants. Cosmetic outcomes in augmented patients treated with breast conservation therapy were reviewed. Augmented patients presented more frequently with palpable lesions, invasive tumors, axillary nodal metastases, and false-negative mammograms. However, there was no significant difference in stage of disease, tumor size, recurrence rates, or survival between the two groups. Augmented patients treated with breast conservation therapy often experienced poor cosmetic results and frequently required reoperation. Despite the diminished sensitivity of mammography in women with implants, augmented and nonaugmented patients are diagnosed at a similar stage of disease and have a comparable prognosis. Implants may impair mammography but appear to facilitate tumor detection on physical examination. Magnetic resonance imaging and breast ultrasound may be useful adjuncts, but conventional mammography remains the most reliable tool for diagnosing early breast cancer in augmented patients. Breast implants do not interfere with mastectomy or breast reconstruction but may compromise the outcome of breast conservation therapy.

In-plane anisotropic strain of elastically and plastically deformed III-nitrides on lithium gallate

Energy Technology Data Exchange (ETDEWEB)

Namkoong, Gon, E-mail: gnamkoon@odu.ed [Old Dominion University, Electrical and Computer Engineering, Applied Research Center, 12050 Jefferson Avenue, Newport News, VA 23606 (United States); Huang, Sa; Moseley, Michael; Doolittle, W. Alan [Georgia Institute of Technology, School of Electrical and Computer Engineering, 777 Atlantic Dr., Atlanta, GA 30332 (United States)

2009-10-30

We have investigated both elastically and plastically deformed GaN films on lithium gallate, LiGaO{sub 2}, by molecular beam epitaxy. The in-plane lattice parameters were determined from high resolution X-ray diffraction and indicated two different groups of in-plane lattice parameters, influenced by the a- and b-axis of LiGaO{sub 2}. The measured in-plane lattice parameters indicate that there exist both compressive and tensile strains of in-plane GaN along the a- and b-axis of LiGaO{sub 2}, respectively. This anisotropic strain in GaN films forms a slight distortion of the basal-plane hexagonal structure of GaN films, leading to a different critical thickness of 4.0 {+-} 0.17 and 7.8 {+-} 0.7 nm along the a- and b-axis of LiGaO{sub 2}, respectively.

In-plane anisotropic strain of elastically and plastically deformed III-nitrides on lithium gallate

International Nuclear Information System (INIS)

Namkoong, Gon; Huang, Sa; Moseley, Michael; Doolittle, W. Alan

2009-01-01

We have investigated both elastically and plastically deformed GaN films on lithium gallate, LiGaO 2 , by molecular beam epitaxy. The in-plane lattice parameters were determined from high resolution X-ray diffraction and indicated two different groups of in-plane lattice parameters, influenced by the a- and b-axis of LiGaO 2 . The measured in-plane lattice parameters indicate that there exist both compressive and tensile strains of in-plane GaN along the a- and b-axis of LiGaO 2 , respectively. This anisotropic strain in GaN films forms a slight distortion of the basal-plane hexagonal structure of GaN films, leading to a different critical thickness of 4.0 ± 0.17 and 7.8 ± 0.7 nm along the a- and b-axis of LiGaO 2 , respectively.

Breast MR imaging in women at high-risk of breast cancer. Is something changing in early breast cancer detection?

International Nuclear Information System (INIS)

Sardanelli, Francesco; Podo, Franca

2007-01-01

In the last few years, several papers have addressed the introduction of contrast-enhanced MR imaging for screening women at high risk for breast cancer. Taking in consideration five prospective studies, on 3,571 screened women with hereditary predisposition to the disease and 9,652 rounds, we found that 168 patients were diagnosed with breast cancer (155 screen-detected, eight interval, and five cancers excluded from analysis) with a detection rate per year of 1.7%. These cancers were small (49% equal to or less than 10 mm in diameter) but aggressive, 82% being invasive and 49% with histologic grade 3; however, only 19% of these invasive cancers were associated with nodal involvement. The pooled sensitivity was 16% for clinical breast examination, 40% for mammography, 43% for ultrasound, and 81% for MR. The positive predictive value (calculated on the basis of the number of invasive diagnostic procedures due to false positives) was 33%, 47%, 18%, and 53%, respectively. Aim of the present article is to present the historical development of MR imaging of breast tumors that made this application theoretically and technically possible, to explain what strategic problems we face in the presence of a hereditary predisposition to the disease, to review the main results of the published studies, and to outline open problems and future perspectives. (orig.)

Efficacy of helical CT in evaluating local tumor extent of breast cancer

International Nuclear Information System (INIS)

Ozaki, Yutaka

2001-01-01

The purpose of this study is to clarify the diagnostic accuracy of helical CT (HCT) in the determination of local tumor extent of breast cancer. One hundred forty consecutive patients with breast cancer, including 87 invasive ductal carcinomas without extensive intraductal components (EIC), 44 invasive ductal carcinomas with EIC, 2 non-invasive ductal carcinomas, and 7 invasive lobular carcinomas, were included in the study. Three-dimensional tumor diameter including whole extent was measured on HCT, and the amount of invasion to fat tissue, skin, pectoral muscle, and chest wall was estimated using a three-step scale. These results were then compared with the pathological findings. Breast cancers appeared as areas of high attenuation compared with the surrounding breast tissue in all patients. Tumor extent was correctly diagnosed by HCT to within a maximum difference of 1 cm in 88 patients (63%) and within 2 cm in 122 patients (87%). Sensitivity, specificity, and accuracy in diagnosing muscular invasion of breast cancer using HCT were 100%, 99%, and 99%, respectively. Sensitivity, specificity, and accuracy in diagnosing skin invasion of breast cancer using HCT were 84%, 93%, and 91%, respectively. HCT was able to visualize all of the tumors and detect the correct tumor extent in most patients. (author)

Efficacy of helical CT in evaluating local tumor extent of breast cancer

Energy Technology Data Exchange (ETDEWEB)

Ozaki, Yutaka [Juntendo Univ., Chiba (Japan). Urayasu Hospital

2001-04-01

The purpose of this study is to clarify the diagnostic accuracy of helical CT (HCT) in the determination of local tumor extent of breast cancer. One hundred forty consecutive patients with breast cancer, including 87 invasive ductal carcinomas without extensive intraductal components (EIC), 44 invasive ductal carcinomas with EIC, 2 non-invasive ductal carcinomas, and 7 invasive lobular carcinomas, were included in the study. Three-dimensional tumor diameter including whole extent was measured on HCT, and the amount of invasion to fat tissue, skin, pectoral muscle, and chest wall was estimated using a three-step scale. These results were then compared with the pathological findings. Breast cancers appeared as areas of high attenuation compared with the surrounding breast tissue in all patients. Tumor extent was correctly diagnosed by HCT to within a maximum difference of 1 cm in 88 patients (63%) and within 2 cm in 122 patients (87%). Sensitivity, specificity, and accuracy in diagnosing muscular invasion of breast cancer using HCT were 100%, 99%, and 99%, respectively. Sensitivity, specificity, and accuracy in diagnosing skin invasion of breast cancer using HCT were 84%, 93%, and 91%, respectively. HCT was able to visualize all of the tumors and detect the correct tumor extent in most patients. (author)

ABRAXAS (FAM175A) and Breast Cancer Susceptibility: No Evidence of Association in the Breast Cancer Family Registry.

Science.gov (United States)

Renault, Anne-Laure; Lesueur, Fabienne; Coulombe, Yan; Gobeil, Stéphane; Soucy, Penny; Hamdi, Yosr; Desjardins, Sylvie; Le Calvez-Kelm, Florence; Vallée, Maxime; Voegele, Catherine; Hopper, John L; Andrulis, Irene L; Southey, Melissa C; John, Esther M; Masson, Jean-Yves; Tavtigian, Sean V; Simard, Jacques

2016-01-01

Approximately half of the familial aggregation of breast cancer remains unexplained. This proportion is less for early-onset disease where familial aggregation is greater, suggesting that other susceptibility genes remain to be discovered. The majority of known breast cancer susceptibility genes are involved in the DNA double-strand break repair pathway. ABRAXAS is involved in this pathway and mutations in this gene impair BRCA1 recruitment to DNA damage foci and increase cell sensitivity to ionizing radiation. Moreover, a recurrent germline mutation was reported in Finnish high-risk breast cancer families. To determine if ABRAXAS could be a breast cancer susceptibility gene in other populations, we conducted a population-based case-control mutation screening study of the coding exons and exon/intron boundaries of ABRAXAS in the Breast Cancer Family Registry. In addition to the common variant p.Asp373Asn, sixteen distinct rare variants were identified. Although no significant difference in allele frequencies between cases and controls was observed for the identified variants, two variants, p.Gly39Val and p.Thr141Ile, were shown to diminish phosphorylation of gamma-H2AX in MCF7 human breast adenocarcinoma cells, an important biomarker of DNA double-strand breaks. Overall, likely damaging or neutral variants were evenly represented among cases and controls suggesting that rare variants in ABRAXAS may explain only a small proportion of hereditary breast cancer.

Diagnostic accuracy of contrast-enhanced spectral mammography in comparison to conventional full-field digital mammography in a population of women with dense breasts.

Science.gov (United States)

Mori, Miki; Akashi-Tanaka, Sadako; Suzuki, Satoko; Daniels, Murasaki Ikeda; Watanabe, Chie; Hirose, Masanori; Nakamura, Seigo

2017-01-01

Contrast-enhanced spectral mammography to compare clinical efficacy of contrast-enhanced spectral mammography (CESM) and conventional digital mammography (MMG) with histopathology as gold standard in dense breasts. A total of 143 breasts of 72 women who underwent CESM and MMG between 2011 and 2014 at Showa University Hospital were analyzed. 129 (90.2 %) of 143 breasts revealed dense breasts on MMG. 58 (40.6 %) of 143 breasts were diagnosed with breast cancer at histopathology. The remaining 85 breasts were diagnosed with benign findings after image assessments and/or core needle biopsy. CESM revealed 8 false-negative cases among 58 breast cancer cases (sensitivity 86.2 %) and 5 false-positive cases (specificity 94.1 %). Accuracy was 90.9 %. Conventional MMG was assessed true positive in 31 of 58 breast cancer cases (sensitivity 53.4 %) and false positive in 12 cases (specificity 85.9 %). Accuracy was 72.7 %. Sensitivity (p < 0.001), specificity (p = 0.016) and accuracy (p < 0.001) were significantly higher on CESM compared to MMG. MMG missed malignancy in 27 breasts. Of these, 25 were dense breasts. Of these 25, 20 (80.0 %) breasts were positive on CESM. These findings suggest that CESM offers superior clinical performance compared to MMG. Use of CESM may decrease false negatives especially for women with dense breasts.

Association between power law coefficients of the anatomical noise power spectrum and lesion detectability in breast imaging modalities

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Chen, Lin; Abbey, Craig K.; Boone, John M.

2013-03-01

Previous research has demonstrated that a parameter extracted from a power function fit to the anatomical noise power spectrum, β, may be predictive of breast mass lesion detectability in x-ray based medical images of the breast. In this investigation, the value of β was compared with a number of other more widely used parameters, in order to determine the relationship between β and these other parameters. This study made use of breast CT data sets, acquired on two breast CT systems developed in our laboratory. A total of 185 breast data sets in 183 women were used, and only the unaffected breast was used (where no lesion was suspected). The anatomical noise power spectrum computed from two-dimensional region of interests (ROIs), was fit to a power function (NPS(f) = α f-β), and the exponent parameter (β) was determined using log/log linear regression. Breast density for each of the volume data sets was characterized in previous work. The breast CT data sets analyzed in this study were part of a previous study which evaluated the receiver operating characteristic (ROC) curve performance using simulated spherical lesions and a pre-whitened matched filter computer observer. This ROC information was used to compute the detectability index as well as the sensitivity at 95% specificity. The fractal dimension was computed from the same ROIs which were used for the assessment of β. The value of β was compared to breast density, detectability index, sensitivity, and fractal dimension, and the slope of these relationships was investigated to assess statistical significance from zero slope. A statistically significant non-zero slope was considered to be a positive association in this investigation. All comparisons between β and breast density, detectability index, sensitivity at 95% specificity, and fractal dimension demonstrated statistically significant association with p performance. Specifically, lower values of β were associated with lower breast density

BREAST RECONSTRUCTIONS AFTER BREAST CANCER TREATING

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Erik Vrabič

2018-02-01

Full Text Available Background. Breasts are an important symbol of physical beauty, feminity, mothering and sexual desire through the entire history of mankind. Lost of the whole or part of the breast is functional and aesthetic disturbance for woman. It is understandable, that the woman, who is concerned over breast loss, is as appropriate as another person´s concern over the loss of a limb or other body part. Before the 1960, breast reconstruction was considered as a dangerous procedure and it was almost prohibited. Considering the psychological importance of the breast in modern society, the possibility of breast reconstruction for the woman about to undergo a mastectomy is a comforting alternative. We can perform breast reconstruction with autologous tissue (autologous reconstruction, with breast implants and combination of both methods. For autologous reconstruction we can use local tissue (local flaps, or tissue from distant parts of the body (free vascular tissue transfer. Tissue expansion must be performed first, in many cases of breast reconstructions with breast implants. Conclusions. Possibility of breast reconstruction made a big progress last 3 decades. Today we are able to reconstruct almost every defect of the breast and the entire breast. Breast reconstruction rise the quality of life for breast cancer patients. Breast reconstruction is a team work of experts from many medicine specialites. In Slovenia we can offer breast reconstruction for breast cancer patients in Ljubljana, where plastic surgeons from Clinical Department for Plastic Surgery and Burns cooperate with oncologic surgeons. Ten years ago a similar cooperation between plastic surgeons and surgeons of the Centre for Breast Diseases was established in Maribor.

Imaging of common breast implants and implant-related complications: A pictorial essay.

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Shah, Amisha T; Jankharia, Bijal B

2016-01-01

The number of women undergoing breast implant procedures is increasing exponentially. It is, therefore, imperative for a radiologist to be familiar with the normal and abnormal imaging appearances of common breast implants. Diagnostic imaging studies such as mammography, ultrasonography, and magnetic resonance imaging are used to evaluate implant integrity, detect abnormalities of the implant and its surrounding capsule, and detect breast conditions unrelated to implants. Magnetic resonance imaging of silicone breast implants, with its high sensitivity and specificity for detecting implant rupture, is the most reliable modality to asses implant integrity. Whichever imaging modality is used, the overall aim of imaging breast implants is to provide the pertinent information about implant integrity, detect implant failures, and to detect breast conditions unrelated to the implants, such as cancer.

TRIB3 protein denotes a good prognosis in breast cancer patients and is associated with hypoxia sensitivity

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Wennemers, Marloes; Bussink, Johan; Grebenchtchikov, Nicolai; Sweep, Fred C.G.J.; Span, Paul N.

2011-01-01

Background: Tribbles homolog 3 (TRIB3) is a pseudokinase involved in the regulation of several signaling pathways involved in cell survival and/or cell stress. Here, we determined the correlation between breast cancer prognosis and TRIB3 protein levels and established the role of TRIB3 in cell survival after hypoxia and/or radiotherapy. Material and methods: TRIB3 mRNA and protein were quantified in a new independent breast cancer patient cohort using QPCR and a new specific avian antibody against TRIB3. In addition, we used siRNA-mediated knockdown of TRIB3 in a colony-forming assay after hypoxia and radiotherapy. Results: TRIB3 mRNA and protein levels did not correlate in breast cancer cell lines or human breast cancer material. We validated our earlier finding that high TRIB3 mRNA denotes a poor prognosis, but found that high TRIB3 protein levels were associated with a good prognosis in breast cancer patients. We also show that knockdown of TRIB3 resulted in an increased survival under hypoxic conditions. Conclusion: Whereas mRNA levels of TRIB3 are related with a poor prognosis, TRIB3 protein is associated with a good prognosis in human breast cancer patients, possibly due to the fact that TRIB3 is involved in hypoxia tolerance.

Ultrasound as a secondary screening tool in mammographically dense breasts

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Griggs, Kylie

2006-01-01

It is well known that breast screening is a part of our society and is designed to reduce the mortality and morbidity from breast cancer. Mammography is the imaging modality of choice in a breast-screening environment. Both the detection rate of mammography in a screening environment and the sensitivity of mammography in symptomatic women are known to be greater than that of ultrasound. However, after a review of literature both of these are said to increase when the two imaging modalities are combined. This paper will present that mammography has limitation

3.0 Tesla breast magnetic resonance imaging in patients with nipple discharge when mammography and ultrasound fail.

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Lubina, Nóra; Schedelbeck, Ulla; Roth, Anne; Weng, Andreas Max; Geissinger, Eva; Hönig, Arnd; Hahn, Dietbert; Bley, Thorsten Alexander

2015-05-01

To compare 3.0 Tesla breast magnetic resonance imaging (MRI) with galactography for detection of benign and malignant causes of nipple discharge in patients with negative mammography and ultrasound. We prospectively evaluated 56 breasts of 50 consecutive patients with nipple discharge who had inconspicuous mammography and ultrasound, using 3.0 Tesla breast MRI with a dedicated 16-channel breast coil, and then compared the results with galactography. Histopathological diagnoses and follow-ups were used as reference standard. Lesion size estimated on MRI was compared with the size at histopathology. Sensitivity and specificity of MRI vs. galactography for detecting pathologic findings were 95.7 % vs. 85.7 % and 69.7 % vs. 33.3 %, respectively. For the supposed concrete pathology based on MRI findings, the specificity was 67.6 % and the sensitivity 77.3 % (PPV 60.7 %, NPV 82.1 %). Eight malignant lesions were detected (14.8 %). The estimated size at breast MRI showed excellent correlation with the size at histopathology (Pearson's correlation coefficient 0.95, p 3.0 Tesla is an accurate imaging test and can replace galactography in the workup of nipple discharge in patients with inconspicuous mammography and ultrasound. • Breast MRI is an excellent diagnostic tool for patients with nipple discharge. • MRI of the breast reveals malignant lesions despite inconspicuous mammography and ultrasound. • MRI of the breast has greater sensitivity and specificity than galactography. • Excellent correlation of lesion size measured at MRI and histopathology was found.

Fuzzy method for pre-diagnosis of breast cancer from the Fine Needle Aspirate analysis

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Sizilio Gláucia RMA

2012-11-01

Full Text Available Abstract Background Across the globe, breast cancer is one of the leading causes of death among women and, currently, Fine Needle Aspirate (FNA with visual interpretation is the easiest and fastest biopsy technique for the diagnosis of this deadly disease. Unfortunately, the ability of this method to diagnose cancer correctly when the disease is present varies greatly, from 65% to 98%. This article introduces a method to assist in the diagnosis and second opinion of breast cancer from the analysis of descriptors extracted from smears of breast mass obtained by FNA, with the use of computational intelligence resources - in this case, fuzzy logic. Methods For data acquisition of FNA, the Wisconsin Diagnostic Breast Cancer Data (WDBC, from the University of California at Irvine (UCI Machine Learning Repository, available on the internet through the UCI domain was used. The knowledge acquisition process was carried out by the extraction and analysis of numerical data of the WDBC and by interviews and discussions with medical experts. The PDM-FNA-Fuzzy was developed in four steps: 1 Fuzzification Stage; 2 Rules Base; 3 Inference Stage; and 4 Defuzzification Stage. Performance cross-validation was used in the tests, with three databases with gold pattern clinical cases randomly extracted from the WDBC. The final validation was held by medical specialists in pathology, mastology and general practice, and with gold pattern clinical cases, i.e. with known and clinically confirmed diagnosis. Results The Fuzzy Method developed provides breast cancer pre-diagnosis with 98.59% sensitivity (correct pre-diagnosis of malignancies; and 85.43% specificity (correct pre-diagnosis of benign cases. Due to the high sensitivity presented, these results are considered satisfactory, both by the opinion of medical specialists in the aforementioned areas and by comparison with other studies involving breast cancer diagnosis using FNA. Conclusions This paper presents an

Surface TRAIL decoy receptor-4 expression is correlated with TRAIL resistance in MCF7 breast cancer cells

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Sanlioglu, Ahter D; Dirice, Ercument; Aydin, Cigdem; Erin, Nuray; Koksoy, Sadi; Sanlioglu, Salih

2005-01-01

Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells. Despite this promising feature, TRAIL resistance observed in cancer cells seriously challenged the use of TRAIL as a death ligand in gene therapy. The current dispute concerns whether or not TRAIL receptor expression pattern is the primary determinant of TRAIL sensitivity in cancer cells. This study investigates TRAIL receptor expression pattern and its connection to TRAIL resistance in breast cancer cells. In addition, a DcR2 siRNA approach and a complementary gene therapy modality involving IKK inhibition (AdIKKβKA) were also tested to verify if these approaches could sensitize MCF7 breast cancer cells to adenovirus delivery of TRAIL (Ad5hTRAIL). TRAIL sensitivity assays were conducted using Molecular Probe's Live/Dead Cellular Viability/Cytotoxicity Kit following the infection of breast cancer cells with Ad5hTRAIL. The molecular mechanism of TRAIL induced cell death under the setting of IKK inhibition was revealed by Annexin V binding. Novel quantitative Real Time RT-PCR and flow cytometry analysis were performed to disclose TRAIL receptor composition in breast cancer cells. MCF7 but not MDA-MB-231 breast cancer cells displayed strong resistance to adenovirus delivery of TRAIL. Only the combinatorial use of Ad5hTRAIL and AdIKKβKA infection sensitized MCF7 breast cancer cells to TRAIL induced cell death. Moreover, novel quantitative Real Time RT-PCR assays suggested that while the level of TRAIL Decoy Receptor-4 (TRAIL-R4) expression was the highest in MCF7 cells, it was the lowest TRAIL receptor expressed in MDA-MB-231 cells. In addition, conventional flow cytometry analysis demonstrated that TRAIL resistant MCF7 cells exhibited substantial levels of TRAIL-R4 expression but not TRAIL decoy receptor-3 (TRAIL-R3) on surface. On the contrary, TRAIL sensitive MDA-MB-231 cells displayed very low levels of surface TRAIL-R4

Preclinical study of diagnostic performances of contrast-enhanced spectral mammography versus MRI for breast diseases in China.

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Wang, Qingguo; Li, Kangan; Wang, Lihui; Zhang, Jianbing; Zhou, Zhiguo; Feng, Yan

2016-01-01

To evaluate diagnostic performances of CESM for breast diseases with comparison to breast MRI in China. Sixty-eight patients with 77 breast lesions underwent MR and CESM. Two radiologists interpreted either MRI or CESM images, separately and independently. BI-RADS 1-3 and BI-RADS 4-5 were classified into the suspicious benign and suspicious malignant groups. Diagnostic accuracy parameters were calculated. Receiver operating characteristic (ROC) curves were constructed for the two modalities. The agreement and correlation between maximum lesion diameter based on CESM and MRI, or CESM and pathology were analyzed. Diagnostic accuracy parameters for CESM were sensitivity 95.8 %, specificity 65.5 %, PPV 82.1 %, NPV 90.5 % and accuracy 84.4 %. The diagnostic accuracy parameters for breast MRI were sensitivity 93.8 %, specificity 82.8 %, PPV 88.2 %, NPV 92.3 %and accuracy 89.6 %. Area under the curve (AUC) of ROC was 0.96 for breast MRI and 0.88 for CESM. The Bland-Altman plots showed a mean difference of 0.7 mm with 95 % limits of agreement of 11.4 mm in tumor diameter measured using CESM and breast MRI. The differences of size measurement between CESM and breast MRI were significant, whereas no difference was observed between CESM and pathology as well as between breast MRI and pathology. The better correlation with pathological results was found in CESM than breast MRI. Our study demonstrates that CESM possesses better diagnostic performances than breast MRI in terms of diagnostic sensitivity and lesion size assessment. And CESM is a good alternative method of screening breast cancer in high-risk people.

Comparison of intraductal spread on dynamic contrast-enhanced MRI with clinicopathologic features in breast cancer

International Nuclear Information System (INIS)

Komatsu, Shuhei; Lee, Chol-Joo; Hosokawa, Yohei; Ichikawa, Daisuke; Hamashima, Takashi; Shirono, Koichi; Okabe, Harumi; Kurioka, Hideaki; Oka, Takahiro

2004-01-01

Contrast-enhanced magnetic resonance imaging (CE-MRI) has emerged as a new diagnostic technology in various breast cancer treatments. However, little is known about the correlation between intraductal spread on CE-MRI and clinicopathologic features. This study was designed to evaluate these correlations for the surgical planning of breast cancer. Twenty-six breast cancer lesions (in 26 female patients) treated by breast conserving surgery between March 2001 and March 2003 were evaluated retrospectively. CE-MRI was performed with a 1.5 T unit using a dedicated bilateral breast coil. In detecting intraductal spread of breast cancer, the sensitivity, specificity and accuracy of CE-MRI were 82.4%, 60.0% and 77.3%, respectively. On mammography (MMG), these were 21.1%, 100.0% and 42.3%, respectively. Therefore, CE-MRI has a higher sensitivity and accuracy, although with a lower specificity than MMG. Compared with breast cancer lesions without intraductal spread on CE-MRI, lesions with intraductal spread on CE-MRI were found more frequently in larger-sized tumors (P=0.0088). Preoperative evaluation for intraductal spread by CE-MRI should be more useful than by MMG for breast cancer. When making the surgical decision regarding excision range, particular attention should be paid to this consideration for patients with larger-sized cancer tumors. (author)

Detector design issues for compact nuclear emission cameras dedicated to breast imaging

International Nuclear Information System (INIS)

Levin, Craig S.

2003-01-01

Certain gamma ray and positron emitting radiotracers have shown great promise for use in the detection, diagnosis and staging of breast cancer. Unfortunately, standard nuclear emission cameras (SPECT, PET) found in the clinic are not practical for breast imaging of these emissions due to inadequate spatial and energy resolutions and sensitivity, large and awkward size, and relatively high cost per study. High spatial and energy resolutions and sensitivity are needed for good lesion detectability. Due to these limitations of standard cameras, there has been recent research into the development of small, compact nuclear emission imagers dedicated for close-proximity breast imaging. The small detector head size means a variety of exotic detectors or collimators may be implemented to improve spatial and energy resolution and sensitivity performances at a reasonable cost. In this paper, we will present some of the compact gamma ray and annihilation photon imaging detector designs that have been proposed and/or developed for dedicated breast imaging. We will review the physics and discuss the advantages and disadvantages of various detector configurations. Finally we will estimate the fundamental spatial resolution potential available with close-proximity nuclear emission imaging and discuss how one may approach those limits through proper detector design

Epigallocatechin-3-gallate accelerates relaxation and Ca2+ transient decay and desensitizes myofilaments in healthy and Mybpc3-targeted knock-in cardiomyopathic mice

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Felix W. Friedrich

2016-12-01

Full Text Available Background. Hypertrophic cardiomyopathy (HCM is the most common inherited cardiac muscle disease with left ventricular hypertrophy, interstitial fibrosis and diastolic dysfunction. Increased myofilament Ca2+ sensitivity could be the underlying cause of diastolic dysfunction. Epigallocatechin-3-gallate (EGCg, a catechin found in green tea has, been reported to decrease myofilament Ca2+ sensitivity in HCM models with troponin mutations. However, whether this is also the case for HCM-associated thick filament mutations is not known. Therefore, we evaluated whether EGCg affects the behavior of cardiomyocytes and myofilaments of a HCM mouse model carrying a gene mutation in cardiac myosin-binding protein C and exhibiting both increased myofilament Ca2+ sensitivity and diastolic dysfunction.Methods and Results. Acute effects of EGCg were tested on fractional sarcomere shortening and Ca2+ transients in intact ventricular myocytes and on force-Ca2+ relationship of skinned ventricular muscle strips isolated from Mybpc3-targeted knock-in (KI and wild-type (WT mice. Fractional sarcomere shortening and Ca2+ transients were analyzed at 37 °C under 1-Hz pacing in the absence or presence of EGCg (1.8 µM. At baseline and in the absence of Fura-2, KI cardiomyocytes displayed lower diastolic sarcomere length, higher fractional sarcomere shortening, longer time to peak shortening and time to 50% relengthening than WT cardiomyocytes. In WT and KI neither diastolic sarcomere length nor fractional sarcomere shortening were influenced by EGCg treatment, but relaxation time was reduced, to a greater extent in KI cells. EGCg shortened time to peak Ca2+ and Ca2+ transient decay in Fura-2-loaded WT and KI cardiomyocytes. EGCg did not influence phosphorylation of phospholamban. In skinned cardiac muscle strips, EGCg (30 µM decreased Ca2+ sensitivity in both groups. Conclusion. EGCg fastened relaxation and Ca2+ transient decay to a larger extent in KI than in WT

Impact of 5-aza-2'-deoxycytidine and epigallocatechin-3-gallate for induction of human regulatory T cells.

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Kehrmann, Jan; Tatura, Roman; Zeschnigk, Michael; Probst-Kepper, Michael; Geffers, Robert; Steinmann, Joerg; Buer, Jan

2014-07-01

The epigenetic regulation of transcription factor genes is critical for T-cell lineage specification. A specific methylation pattern within a conserved region of the lineage specifying transcription factor gene FOXP3, the Treg-specific demethylated region (TSDR), is restricted to regulatory T (Treg) cells and is required for stable expression of FOXP3 and suppressive function. We analysed the impact of hypomethylating agents 5-aza-2'-deoxycytidine and epigallocatechin-3-gallate on human CD4(+)  CD25(-) T cells for generating demethylation within FOXP3-TSDR and inducing functional Treg cells. Gene expression, including lineage-specifying transcription factors of the major T-cell lineages and their leading cytokines, functional properties and global transcriptome changes were analysed. The FOXP3-TSDR methylation pattern was determined by using deep amplicon bisulphite sequencing. 5-aza-2'-deoxycytidine induced FOXP3-TSDR hypomethylation and expression of the Treg-cell-specific genes FOXP3 and LRRC32. Proliferation of 5-aza-2'-deoxycytidine-treated cells was reduced, but the cells did not show suppressive function. Hypomethylation was not restricted to FOXP3-TSDR and expression of master transcription factors and leading cytokines of T helper type 1 and type 17 cells were induced. Epigallocatechin-3-gallate induced global DNA hypomethylation to a lesser extent than 5-aza-2'-deoxycitidine, but no relevant hypomethylation within FOXP3-TSDR or expression of Treg-cell-specific genes. Neither of the DNA methyltransferase inhibitors induced fully functional human Treg cells. 5-aza-2'-deoxycitidine-treated cells resembled Treg cells, but they did not suppress proliferation of responder cells, which is an essential capability to be used for Treg cell transfer therapy. Using a recently developed targeted demethylation technology might be a more promising approach for the generation of functional Treg cells. © 2014 John Wiley & Sons Ltd.

Effects of fluoride and epigallocatechin gallate on soft-drink-induced dental erosion of enamel and root dentin

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Yin-Lin Wang

2018-04-01

Full Text Available Background/Purpose: Fluoride and epigallocatechin gallate (EGCG have been proven to prevent dental caries. The purpose of this study was to evaluate the effects of fluoride and EGCG on soft-drink-induced dental erosion in vitro. Methods: Forty enamel and dentin specimens were prepared from extracted human teeth. The specimens were divided into 4 groups and treated separately with distilled water (as control, 0.5 M sodium fluoride (NF, 400 μM EGCG (EG, and a solution containing 0.5 M NaF and 400 μM EGCG (FG. Cyclic erosive treatment was performed according to the experimental procedures. The specimens were analyzed using laser scanning confocal microscopy, scanning electron microscopy, and a microhardness tester. The data were analyzed using ANOVA and Bonferroni's post hoc test. The significance level was set at 5%. Results: The amount of substance loss was lower in the NF and EG groups than in the control group (p < 0.05. The erosion-caused substance loss was more pronounced in the dentin than in the enamel specimens. Surface microhardness loss was lower in the NF and EG groups than in the control group (p < 0.05. The diameter of the dentinal tubule was wider in the control group than in the NF and EG groups (p < 0.05. No combined effects were observed in the FG group. Conclusion: Both fluoride and EGCG are effective in preventing soft-drink-induced erosion compared with the control group. Fluoride and EGCG may interfere with each other. The mechanisms of the anti-erosive effect need to be explored in the future. Keywords: Dental erosion, Fluoride, Epigallocatechin gallate, Soft drinks, Laser scanning confocal microscopy

The research on distinguishing benign from malignant breast lesions by diffusion-weighted MR imaging

International Nuclear Information System (INIS)

Zhao Bin; Peng Hongjuan; Cai Shifeng; Gao Peihong

2005-01-01

Objective: To investigate the value of apparent diffusion coefficient (ADC) of diffusion- weighted magnetic resonance imaging (DW-MRI) in distinguishing benign from malignant breast lesions. Methods: ADC in 26 normal breasts, 24 malignant breast lesions, and 30 benign breast lesions confirmed by operation and pathology were calculated, respectively, and their differentiations in statistics were compared. The differentiations of different ADCs (b=1000-0, 500-0, 1000-500 s/mm 2 ) were also compared. EPI (TR 2900 ms, TE 84 ms, thickness 5 mm) was used in order to acquire the imaging. Results: There were significant differences among the ADC values of normal breast tissue, benign, and malignant lesions. The ADC of malignant lesions was lower than those of normal breast tissue and benign lesions, and the ADC of benign lesions was lower than that of normal breast tissue. There were significant differences among the ADC value of b=1000-0, 1000-500, and 500-0 s/mm 2 . The lower the b value, the higher the ADC. The sensitivity and specificity of ADC for the diagnosis of malignant lesion were 64% and 96.7% if the upper bound of 95% confidence interval was set as a differential level. Conclusion: The differentiation of benign from malignant breast lesions by ADC is applicable, although the sensitivity is low, the specificity is high. (authors)

Accuracy of technetium-99m sestamibi scintimammography and X-ray mammography in premenopausal women with suspected breast cancer

International Nuclear Information System (INIS)

Lumachi, F.; Ferretti, G.; Povolato, M.; Geatti, O.; Marzola, M.C.; Zucchetta, P.; Bui, F.; Brandes, A.A.

2001-01-01

The aim of this study was to evaluate the usefulness of technetium-99m sestamibi scintimammography (SSM) and combined use of SSM and X-ray mammography (MG) in premenopausal patients with small (≤2 cm) suspicious breast lesions. Eighty-seven premenopausal women (median age 47 years, range 32-52) with breast lesions ranging from 4 to 20 mm in greatest diameter (median 12 mm) and detected by MG, underwent SSM prior to open breast biopsy. A planar camera and single-photon emission tomography (SPET) technique were used in 23 (26.4%) and 64 (73.6%) patients, respectively. At histological examination, 72 (82.8%) breast cancers (pT1a=3, pT1b=27, pT1c=42) and 15 (17.2%) benign masses were found. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of MG and SSM were 80.6% vs 80.6%, 60.0% vs 93.3% (P<0.05), 90.6% vs 98.3%, 39.1% vs 50.0% and 77.0% vs 82.8%, respectively. MG + SSM together had a sensitivity of 94.4% (P<0.05 vs SSM alone) and an accuracy of 82.8% for the detection of breast cancer. Tumours undetected by both MG and SSM were significantly (P<0.05) smaller than those correctly diagnosed. Patients with false-negative MG were younger (P<0.05) than those with tumours correctly detected, while SSM sensitivity was independent (P=NS) of age. In conclusion, in premenopausal patients with small breast lesions, the sensitivity of SSM and MG is similar (P=NS), whereas the specificity of SSM is significantly higher (P<0.05) than that of MG. Furthermore, the combination of MG and SSM offers significantly improved sensitivity and accuracy in comparison with the individual techniques, suggesting a complementary role of SSM in the detection of breast cancer in younger patients. (orig.)

Optical computed tomography for imaging the breast: first look

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Grable, Richard J.; Ponder, Steven L.; Gkanatsios, Nikolaos A.; Dieckmann, William; Olivier, Patrick F.; Wake, Robert H.; Zeng, Yueping

2000-07-01

The purpose of the study is to compare computed tomography optical imaging with traditional breast imaging techniques. Images produced by computed tomography laser mammography (CTLMTM) scanner are compared with images obtained from mammography, and in some cases ultrasound and/or magnetic resonance imaging (MRI). During the CTLM procedure, a near infrared laser irradiates the breast and an array of photodiodes detectors records light scattered through the breast tissue. The laser and detectors rotate synchronously around the breast to acquire a series of slice data along the coronal place. The procedure is performed without any breast compression or optical matching fluid. Cross-sectional slices of the breast are produced using a reconstruction algorithm. Reconstruction based on the diffusion theory is used to produce cross-sectional slices of the breast. Multiple slice images are combined to produce a three dimensional volumetric array of the imaged breast. This array is used to derive axial and sagittal images of the breast corresponding to cranio-caudal and medio-lateral images used in mammography. Over 200 women and 3 men have been scanned in clinical trials. The most obvious features seen in images produced by the optical tomography scanner are vascularization and significant lesions. Breast features caused by fibrocystic changes and cysts are less obvious. Breast density does not appear to be a significant factor in the quality of the image. We see correlation of the optical image structure with that seen with traditional breast imaging techniques. Further testing is being conducted to explore the sensitivity and specificity of optical tomography of the breast.

Machine learning models in breast cancer survival prediction.

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Montazeri, Mitra; Montazeri, Mohadeseh; Montazeri, Mahdieh; Beigzadeh, Amin

2016-01-01

Breast cancer is one of the most common cancers with a high mortality rate among women. With the early diagnosis of breast cancer survival will increase from 56% to more than 86%. Therefore, an accurate and reliable system is necessary for the early diagnosis of this cancer. The proposed model is the combination of rules and different machine learning techniques. Machine learning models can help physicians to reduce the number of false decisions. They try to exploit patterns and relationships among a large number of cases and predict the outcome of a disease using historical cases stored in datasets. The objective of this study is to propose a rule-based classification method with machine learning techniques for the prediction of different types of Breast cancer survival. We use a dataset with eight attributes that include the records of 900 patients in which 876 patients (97.3%) and 24 (2.7%) patients were females and males respectively. Naive Bayes (NB), Trees Random Forest (TRF), 1-Nearest Neighbor (1NN), AdaBoost (AD), Support Vector Machine (SVM), RBF Network (RBFN), and Multilayer Perceptron (MLP) machine learning techniques with 10-cross fold technique were used with the proposed model for the prediction of breast cancer survival. The performance of machine learning techniques were evaluated with accuracy, precision, sensitivity, specificity, and area under ROC curve. Out of 900 patients, 803 patients and 97 patients were alive and dead, respectively. In this study, Trees Random Forest (TRF) technique showed better results in comparison to other techniques (NB, 1NN, AD, SVM and RBFN, MLP). The accuracy, sensitivity and the area under ROC curve of TRF are 96%, 96%, 93%, respectively. However, 1NN machine learning technique provided poor performance (accuracy 91%, sensitivity 91% and area under ROC curve 78%). This study demonstrates that Trees Random Forest model (TRF) which is a rule-based classification model was the best model with the highest level of

A Targetable EGFR-Dependent Tumor-Initiating Program in Breast Cancer

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Paul Savage

2017-10-01

Full Text Available Summary: Therapies targeting epidermal growth factor receptor (EGFR have variable and unpredictable responses in breast cancer. Screening triple-negative breast cancer (TNBC patient-derived xenografts (PDXs, we identify a subset responsive to EGFR inhibition by gefitinib, which displays heterogeneous expression of wild-type EGFR. Deep single-cell RNA sequencing of 3,500 cells from an exceptional responder identified subpopulations displaying distinct biological features, where elevated EGFR expression was significantly enriched in a mesenchymal/stem-like cellular cluster. Sorted EGFRhi subpopulations exhibited enhanced stem-like features, including ALDH activity, sphere-forming efficiency, and tumorigenic and metastatic potential. EGFRhi cells gave rise to EGFRhi and EGFRlo cells in primary and metastatic tumors, demonstrating an EGFR-dependent expansion and hierarchical state transition. Similar tumorigenic EGFRhi subpopulations were identified in independent PDXs, where heterogeneous EGFR expression correlated with gefitinib sensitivity. This provides new understanding for an EGFR-dependent hierarchy in TNBC and for patient stratification for therapeutic intervention. : Savage et al. demonstrate that sensitivity to EGFR inhibitor, gefitinib, in triple-negative breast cancer is paradoxically associated with EGFR heterogeneity. Using single-cell RNA sequencing in conjunction with functional assays, they identify TNBC tumors in which EGFR expression identifies cells with tumor-initiating capacity whose proliferative expansion is sensitive to EGFR inhibition. Keywords: breast cancer, tumor heterogeneity, patient-derived xenograft, single-cell RNA sequencing, EGFR inhibition, therapeutic response, tumor-initiating cell, cell hierarchy, BRCA1 mutation

Review and management of breast lesions detected with breast tomosynthesis but not visible on mammography and ultrasonography.

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Taskin, Fusun; Durum, Yasemin; Soyder, Aykut; Unsal, Alparslan

2017-12-01

Background Breast tomosynthesis is more sensitive than mammography and can detect lesions that are not always visible with conventional methods such as digital mammography (MG) and ultrasonography (US). No standardized approach is available for the management of lesions that are detectable with tomosynthesis but are not visible on MG or US. Purpose To review suspicious breast lesions detected with tomosynthesis but not visible on two-dimensional (2D) MG or US and to determine the management options for these lesions. Material and Methods Ethical committee approval was obtained. The radiological records, biopsy or surgery results, and follow-up findings of 107 patients who had a tomosynthesis-positive but MG- or US-negative breast lesion between 2011 and 2016 were retrospectively evaluated. Results Of 107 lesions visible only with tomosynthesis, 74% were architectural distortions and 26% were asymmetrical opacities. All patients underwent magnetic resonance imaging (MRI) for further evaluation. Among the 48 (45%) MRI-negative lesions, none had a suspicious alteration during the follow-up period. Among the MRI-positive lesions, 28% of the 50 architectural distortions and 11% of the nine asymmetrical opacities were malignant. Conclusion Given the inherent high false-positive rate of breast tomosynthesis, breast MRI prior to biopsy may reduce the number of unnecessary biopsies for suspicious breast lesions that are tomosynthesis-positive only.

Technetium-99m scintimammography in the diagnosis of malignant breast tumors

Directory of Open Access Journals (Sweden)

Jauković Ljiljana

2004-01-01

Full Text Available Background. Technetium-99m (99mTc tetrofosmin scintigraphy is a new imaging method for the diagnosis of various malignancies, such as lung, thyroid, and most frequently breast neoplasms. The aim of this study was to evaluate the diagnostic reliability of 99mTc-Tetrofosmin breast scintigraphy in the detection of malignant breast disease. Methods. 99mTc -Tetrofosmin scintimammography (SMM was performed in 28 patients with 30 breast lesions suspicious for malignancy. Standard mammography (MM was also done. After surgery, the results of SMM and MM were compared to definitive histopathological findings as the "gold standard". After intravenous injection of radiotracer, SMM was performed in prone and supine views of the thorax, using large field-of-view Gamma camera. Results. The results of SMM were interpreted visually and semiquantitatively, and evaluated as positive or negative. Sensitivity, specificity and accuracy, positive (PPV and negative predictive value (NPV were obtained in relation to histopathology. After comparing the results of SMM and MM, SMM was proved more sensitive (95% for SMM vs. 80% for MM, while the specificity of both methods was similar. Conclusion. The results of this study indicate that the contribution of SMM as a nuclear medicine procedure has its place in the diagnostic protocol for patients suspected of malignant breast cancer.

Breast cancer biology for the radiation oncologist

Energy Technology Data Exchange (ETDEWEB)

Strauss, Jonathan [Northwestern Univ., Chicago, IL (United States). Dept. of Radiation Oncology; Small, William [Loyola Univ. Chicago, Maywood, IL (United States). Stritch School of Medicine, Cardianl Bernardin Cancer Center; Woloschak, Gayle E. (ed.) [Northwestern Univ. Feinberg, Chicago, IL (United States). School of Medicine

2015-10-01

This is the first textbook of its kind devoted to describing the biological complexities of breast cancer in a way that is relevant to the radiation oncologist. Radiation Oncology has long treated breast cancer as a single biological entity, with all treatment decisions being based on clinical and pathologic risk factors. We are now beginning to understand that biological subtypes of breast cancer may have different risks of recurrence as well as different intrinsic sensitivity to radiotherapy. Multi-gene arrays that have for years been used to predict the risk of distant recurrence and the value of systemic chemotherapy may also have utility in predicting the risk of local recurrence. Additionally, the targeted agents used to treat breast cancer may interact with radiotherapy in ways that can be beneficial or undesirable. All of these emerging issues are extensively discussed in this book, and practical evidence-based treatment recommendations are presented whenever possible.

Breast cancer biology for the radiation oncologist

International Nuclear Information System (INIS)

Strauss, Jonathan; Small, William; Woloschak, Gayle E.

2015-01-01

This is the first textbook of its kind devoted to describing the biological complexities of breast cancer in a way that is relevant to the radiation oncologist. Radiation Oncology has long treated breast cancer as a single biological entity, with all treatment decisions being based on clinical and pathologic risk factors. We are now beginning to understand that biological subtypes of breast cancer may have different risks of recurrence as well as different intrinsic sensitivity to radiotherapy. Multi-gene arrays that have for years been used to predict the risk of distant recurrence and the value of systemic chemotherapy may also have utility in predicting the risk of local recurrence. Additionally, the targeted agents used to treat breast cancer may interact with radiotherapy in ways that can be beneficial or undesirable. All of these emerging issues are extensively discussed in this book, and practical evidence-based treatment recommendations are presented whenever possible.

Breast Cancer Diagnosis Using Ultrasound and Diffusive Light

National Research Council Canada - National Science Library

Zhu, Quing

2001-01-01

The main goal of this study is to evaluate a novel imaging system and method that combines ultrasound with near infrared diffusive light to increase the sensitivity and specificity of breast cancer detection...

Three-dimensional vascular mapping of the breast by using contrast-enhanced MRI: association of unilateral increased vascularity with ipsilateral breast cancer.

Science.gov (United States)

Orgüç, Şebnem; Başara, Işıl; Coşkun, Teoman; Pekindil, Gökhan

2012-01-01

We aimed to retrospectively compare three-dimensional vascular maps of both breasts obtained by dynamic magnetic resonance imaging (MRI) and determine the association of one-sided vascular prominence with ipsilateral breast cancer. MRI was performed using gadolinium in 194 cases. Two readers scored vascular density using maximum intensity projections (MIPs). Dynamic fat-saturated T1-weighted gradientecho MIPs were acquired. Two readers evaluated the MIPs, and vessels greater than 2 mm in diameter and longer than 3 cm were counted. The difference in vessel numbers detected in the two breasts determined the score. A total of 54 patients had malignant lesions (prevalence, 28%), including invasive ductal carcinoma (n=40), invasive mixed ductal-lobular carcinoma (n=5), invasive lobular carcinoma (n=3), ductal carcinoma in situ (n=3), mucinous carcinoma (n=1), medullary carcinoma (n=1), and leukemic metastasis (n=1). In 62 patients, there were benign lesions (fibroadenomas, fibrocysts), and four patients had inflammation (granulomatous mastitis in two patients, breast tuberculosis in two patients). There were 78 normal cases. When a difference of at least two vessels was scored as vascular asymmetry, the sensitivity, specificity, positive likelihood ratio (+LR), and negative (-LR) of unilaterally increased vascularity associated with ipsilateral malignancy were 69%, 92%, 8.72, and 0.34, respectively. When four infection and three post-operative cases with vascular asymmetry were excluded; prevalence, specificity, and +LR increased to 29%, 97%, and 22.8, respectively, with the same sensitivity and -LR. Differences in mean vascularity scores were evaluated with regard to tumor size. T1 and T2 tumors were not significantly different from each other. The mean score of T3 tumors differed significantly from T1 and T2 tumors. MRI vascular mapping is an effective method for determining breast tissue vascularization. Ipsilateral increased vascularity was commonly associated with

Compositional breast imaging using a dual-energy mammography protocol

International Nuclear Information System (INIS)

Laidevant, Aurelie D.; Malkov, Serghei; Flowers, Chris I.; Kerlikowske, Karla; Shepherd, John A.

2010-01-01

Purpose: Mammography has a low sensitivity in dense breasts due to low contrast between malignant and normal tissue confounded by the predominant water density of the breast. Water is found in both adipose and fibroglandular tissue and constitutes most of the mass of a breast. However, significant protein mass is mainly found in the fibroglandular tissue where most cancers originate. If the protein compartment in a mammogram could be imaged without the influence of water, the sensitivity and specificity of the mammogram may be improved. This article describes a novel approach to dual-energy mammography, full-field digital compositional mammography (FFDCM), which can independently image the three compositional components of breast tissue: water, lipid, and protein. Methods: Dual-energy attenuation and breast shape measures are used together to solve for the three compositional thicknesses. Dual-energy measurements were performed on breast-mimicking phantoms using a full-field digital mammography unit. The phantoms were made of materials shown to have similar x-ray attenuation properties of the compositional compartments. They were made of two main stacks of thicknesses around 2 and 4 cm. Twenty-six thickness and composition combinations were used to derive the compositional calibration using a least-squares fitting approach. Results: Very high accuracy was achieved with a simple cubic fitting function with root mean square errors of 0.023, 0.011, and 0.012 cm for the water, lipid, and protein thicknesses, respectively. The repeatability (percent coefficient of variation) of these measures was tested using sequential images and was found to be 0.5%, 0.5%, and 3.3% for water, lipid, and protein, respectively. However, swapping the location of the two stacks of the phantom on the imaging plate introduced further errors showing the need for more complete system uniformity corrections. Finally, a preliminary breast image is presented of each of the compositional

Computer Aided Detection of Breast Masses in Digital Tomosynthesis

National Research Council Canada - National Science Library

Singh, Swatee; Lo, Joseph

2008-01-01

The purpose of this study was to investigate feasibility of computer-aided detection of masses and calcification clusters in breast tomosynthesis images and obtain reliable estimates of sensitivity...

Collaborative study of a qualitative TLC-method for detection of antioxidants (BHA, BHT, gallates and NDGA) in food

DEFF Research Database (Denmark)

Guldborg, Merethe

1981-01-01

-proposed method, and an official French method. After extraction, the compounds are detected by TLC. Being a qualitative method the probability of obtaining correct results is a measure of the goodness of the method, and the study examines the influence on the probability of the following 3 factors: type...... of antioxidant, type of food, and concentration of antioxidant. From the study is was concluded that the method worked quite well for BHA, with a detection limit about 15 mg/kg, whereas it worked badly for BHT, the detection limit being higher than 30 mg/kg. For the gallates and NDGA the detection limit was 30...

The potential of multiparametric MRI of the breast

Science.gov (United States)

Pinker, Katja; Helbich, Thomas H

2017-01-01

MRI is an essential tool in breast imaging, with multiple established indications. Dynamic contrast-enhanced MRI (DCE-MRI) is the backbone of any breast MRI protocol and has an excellent sensitivity and good specificity for breast cancer diagnosis. DCE-MRI provides high-resolution morphological information, as well as some functional information about neoangiogenesis as a tumour-specific feature. To overcome limitations in specificity, several other functional MRI parameters have been investigated and the application of these combined parameters is defined as multiparametric MRI (mpMRI) of the breast. MpMRI of the breast can be performed at different field strengths (1.5–7 T) and includes both established (diffusion-weighted imaging, MR spectroscopic imaging) and novel MRI parameters (sodium imaging, chemical exchange saturation transfer imaging, blood oxygen level-dependent MRI), as well as hybrid imaging with positron emission tomography (PET)/MRI and different radiotracers. Available data suggest that multiparametric imaging using different functional MRI and PET parameters can provide detailed information about the underlying oncogenic processes of cancer development and progression and can provide additional specificity. This article will review the current and emerging functional parameters for mpMRI of the breast for improved diagnostic accuracy in breast cancer. PMID:27805423

The Role of Protein Elongation Factor EEF1A2 in Breast Cancer

National Research Council Canada - National Science Library

Lee, Jonathan M

2004-01-01

... overexpression can be used as a breast cancer prognostic factor. In addition, we proposed to test the idea that EEF1A2 expression modulates sensitivity to cisplatin and taxol and that EEF1A2-inactivation could be used as a treatment for breast cancer...

Imaging of common breast implants and implant-related complications: A pictorial essay

Directory of Open Access Journals (Sweden)

Amisha T Shah

2016-01-01

Full Text Available The number of women undergoing breast implant procedures is increasing exponentially. It is, therefore, imperative for a radiologist to be familiar with the normal and abnormal imaging appearances of common breast implants. Diagnostic imaging studies such as mammography, ultrasonography, and magnetic resonance imaging are used to evaluate implant integrity, detect abnormalities of the implant and its surrounding capsule, and detect breast conditions unrelated to implants. Magnetic resonance imaging of silicone breast implants, with its high sensitivity and specificity for detecting implant rupture, is the most reliable modality to asses implant integrity. Whichever imaging modality is used, the overall aim of imaging breast implants is to provide the pertinent information about implant integrity, detect implant failures, and to detect breast conditions unrelated to the implants, such as cancer.

Screening mammography-detected cancers: the sensitivity of the computer-aided detection system as applied to full-field digital mammography

International Nuclear Information System (INIS)

Yang, Sang Kyu; Cho, Nariya; Ko, Eun Sook; Kim, Do Yeon; Moon, Woo Kyung

2006-01-01

We wanted to evaluate the sensitivity of the computer-aided detection (CAD) system for performing full-field digital mammography (FFDM) on the breast cancers that were originally detected by screening mammography. The CAD system (Image Checker v3.1, R2 Technology, Los Altos, Calif.) together with a full-field digital mammography system (Senographe 2000D, GE Medical Systems, Buc, France) was prospectively applied to the mammograms of 70 mammographically detected breast cancer patients (age range, 37-69; median age, 51 years) who had negative findings on their clinical examinations. The sensitivity of the CAD system, according to histopathologic findings and radiologic primary features (i.e, mass, microcalcifications or mass with microcalcifications) and also the false-positive marking rate were then determined. The CAD system correctly depicted 67 of 70 breast cancer lesions (97.5%). The CAD system marked 29 of 30 breast cancers that presented with microcalcifications only (sensitivity 96.7%) and all 18 breast cancers the presented with mass together with microcalcifications (sensitivity 100%). Twenty of the 22 lesions that appeared as a mass only were marked correctly by the CAD system (sensitivity 90.9%). The CAD system correctly depicted all 22 lesions of ductal carcinoma in situ (sensitivity: 100%), all 13 lesions of invasive ductal carcinoma with ductal carcinoma in situ (sensitivity: 100%) and the 1 lesion of invasive lobular carcinoma (sensitivity: 100%). Thirty one of the 34 lesions of invasive ductal carcinoma were marked correctly by the CAD system (sensitivity: 91.8%). The rate of false-positive marks was 0.21 mass marks per image and 0.16 microcalcification marks per image. The overall rate of false-positive marks was 0.37 per image. The CAD system using FFDM is useful for the detection of asymptomatic breast cancers, and it has a high overall tumor detection rate. The false negative cases were found in relatively small invasive ductal carcinoma

Screening mammography-detected cancers: the sensitivity of the computer-aided detection system as applied to full-field digital mammography

Energy Technology Data Exchange (ETDEWEB)

Yang, Sang Kyu; Cho, Nariya; Ko, Eun Sook; Kim, Do Yeon; Moon, Woo Kyung [College of Medicine Seoul National University and The Insititute of Radiation Medicine, Seoul National University Research Center, Seoul (Korea, Republic of)

2006-04-15

We wanted to evaluate the sensitivity of the computer-aided detection (CAD) system for performing full-field digital mammography (FFDM) on the breast cancers that were originally detected by screening mammography. The CAD system (Image Checker v3.1, R2 Technology, Los Altos, Calif.) together with a full-field digital mammography system (Senographe 2000D, GE Medical Systems, Buc, France) was prospectively applied to the mammograms of 70 mammographically detected breast cancer patients (age range, 37-69; median age, 51 years) who had negative findings on their clinical examinations. The sensitivity of the CAD system, according to histopathologic findings and radiologic primary features (i.e, mass, microcalcifications or mass with microcalcifications) and also the false-positive marking rate were then determined. The CAD system correctly depicted 67 of 70 breast cancer lesions (97.5%). The CAD system marked 29 of 30 breast cancers that presented with microcalcifications only (sensitivity 96.7%) and all 18 breast cancers the presented with mass together with microcalcifications (sensitivity 100%). Twenty of the 22 lesions that appeared as a mass only were marked correctly by the CAD system (sensitivity 90.9%). The CAD system correctly depicted all 22 lesions of ductal carcinoma in situ (sensitivity: 100%), all 13 lesions of invasive ductal carcinoma with ductal carcinoma in situ (sensitivity: 100%) and the 1 lesion of invasive lobular carcinoma (sensitivity: 100%). Thirty one of the 34 lesions of invasive ductal carcinoma were marked correctly by the CAD system (sensitivity: 91.8%). The rate of false-positive marks was 0.21 mass marks per image and 0.16 microcalcification marks per image. The overall rate of false-positive marks was 0.37 per image. The CAD system using FFDM is useful for the detection of asymptomatic breast cancers, and it has a high overall tumor detection rate. The false negative cases were found in relatively small invasive ductal carcinoma.

Role of multimedial diagnosis of breast cancer in women below 36 year of age

International Nuclear Information System (INIS)

Ciacco, Stefano; Brancato, Beniamino

2005-01-01

Purpose: To evaluate the sensitivity for breast cancer of different diagnostic tests performed in a consecutive series of women aged under 36 years. Materials and methods: The study analyses 155 women with breast cancer incident in the Tuscany Cancer Registry from 1985 to 2000. The sensitivity of each method was evaluated in relation to the most recent test performed during the year before diagnosis and to different variables, such as tumour size and calendar period. Results: Sensitivity was 70.3% for physical examination, 76.0% for mammography, 69.1% for ultrasonography and 80.6% for cytology (86.2% if inadequate samples are excluded). Sensitivity was associated to pT category for physical examination (pT1=60.6%; pT2=4=86.4%; χ2=10.2, p=0.001) and for ultrasonography (pT1=61.9%; pT2=4=92.0%; χ2=5.7, p=0.001) and to breast radiological density for mammography (50-100% density=75.5%; 0-50 density=91.3%; χ2=1.85, p [it

A comprehensive sensitivity analysis of microarray breast cancer classification under feature variability

NARCIS (Netherlands)