Pro-oncogene Pokemon promotes breast cancer progression by upregulating survivin expression

OpenAIRE

Zu, Xuyu; Ma, Jun; Liu, Hongxia; Liu, Feng; Tan, Chunyan; Yu, Lingling; Wang, Jue; Xie, Zhenhua; Cao, Deliang; Jiang, Yuyang

2011-01-01

Introduction Pokemon is an oncogenic transcription factor involved in cell growth, differentiation and oncogenesis, but little is known about its role in human breast cancer. In this study, we aimed to reveal the role of Pokemon in breast cancer progression and patient survival and to understand its underlying mechanisms. Methods Tissue microarray analysis of breast cancer tissues from patients with complete clinicopathological data and more than 20 years of follow-up were used to evaluate Po...

Genomic analyses of breast cancer progression reveal distinct routes of metastasis emergence

DEFF Research Database (Denmark)

Krøigård, Anne Bruun; Larsen, Martin Jakob; Brasch-Andersen, Charlotte

2017-01-01

receptor (ER)-positive breast cancer. Our data provide support for both linear and parallel progression towards metastasis. We report for the first time evidence of metastasis-to-metastasis seeding in breast cancer. Our results point to three distinct routes of metastasis emergence. This may have profound...... clinical implications and provides substantial novel molecular insights into the timing and mutational evolution of breast cancer metastasis....

The neurotensin receptor-1 pathway contributes to human ductal breast cancer progression.

Directory of Open Access Journals (Sweden)

Sandra Dupouy

Full Text Available BACKGROUND: The neurotensin (NTS and its specific high affinity G protein coupled receptor, the NT1 receptor (NTSR1, are considered to be a good candidate for one of the factors implicated in neoplastic progression. In breast cancer cells, functionally expressed NT1 receptor coordinates a series of transforming functions including cellular migration and invasion. METHODS AND RESULTS: we investigated the expression of NTS and NTSR1 in normal human breast tissue and in invasive ductal breast carcinomas (IDCs by immunohistochemistry and RT-PCR. NTS is expressed and up-regulated by estrogen in normal epithelial breast cells. NTS is also found expressed in the ductal and invasive components of IDCs. The high expression of NTSR1 is associated with the SBR grade, the size of the tumor, and the number of metastatic lymph nodes. Furthermore, the NTSR1 high expression is an independent factor of prognosis associated with the death of patients. CONCLUSION: these data support the activation of neurotensinergic deleterious pathways in breast cancer progression.

The tumor macroenvironment and systemic regulation of breast cancer progression.

Science.gov (United States)

Castaño, Zafira; Tracy, Kristin; McAllister, Sandra S

2011-01-01

Breast cancer is the most common malignancy among women worldwide and is the most common cause of death for women between 35 and 50 years of age. Women with breast cancer are at risk of developing metastases for their entire lifetime and, despite local and systemic therapies, approximately 30% of breast cancer patients will relapse (Jemal et al., 2010). Nearly all breast cancer related deaths are due to metastatic disease, even though metastasis is considered to be an inefficient process. In some cases, tumor cells disseminate from primary sites at an early stage, but remain indolent for protracted periods of time before becoming overt, life-threatening tumors. Little is known about the mechanisms that cause these indolent tumors to grow into malignant disease. Because of this gap in our understanding, we are unable to predict which breast cancer patients are likely to experience disease relapse or develop metastases years after treatment of their primary tumor. A better understanding of the mechanisms and signals involved in the exit of tumor cells from dormancy would not only allow for more accurate selection of patients that would benefit from systemic therapy, but could also lead to the development of more targeted therapies to inhibit the signals that promote disease progression. In this review, we address the systemic, or "macroenvironmental", contribution to tumor initiation and progression and what is known about how a pro-tumorigenic systemic environment is established.

Selective expression of long non-coding RNAs in a breast cancer cell progression model.

Science.gov (United States)

Tracy, Kirsten M; Tye, Coralee E; Page, Natalie A; Fritz, Andrew J; Stein, Janet L; Lian, Jane B; Stein, Gary S

2018-02-01

Long non-coding RNAs (lncRNAs) are acknowledged as regulators of cancer biology and pathology. Our goal was to perform a stringent profiling of breast cancer cell lines that represent disease progression. We used the MCF-10 series, which includes the normal-like MCF-10A, HRAS-transformed MCF-10AT1 (pre-malignant), and MCF-10CA1a (malignant) cells, to perform transcriptome wide sequencing. From these data, we have identified 346 lncRNAs with dysregulated expression across the progression series. By comparing lncRNAs from these datasets to those from an additional set of cell lines that represent different disease stages and subtypes, MCF-7 (early stage, luminal), and MDA-MB-231 (late stage, basal), 61 lncRNAs that are associated with breast cancer progression were identified. Querying breast cancer patient data from The Cancer Genome Atlas, we selected a lncRNA, IGF-like family member 2 antisense RNA 1 (IGFL2-AS1), of potential clinical relevance for functional characterization. Among the 61 lncRNAs, IGFL2-AS1 was the most significantly decreased. Our results indicate that this lncRNA plays a role in downregulating its nearest neighbor, IGFL1, and affects migration of breast cancer cells. Furthermore, the lncRNAs we identified provide a valuable resource to mechanistically and clinically understand the contribution of lncRNAs in breast cancer progression. © 2017 Wiley Periodicals, Inc.

The role of technical progress in the process of recalculating oil reserves

International Nuclear Information System (INIS)

Boulard, J.N.

1999-01-01

Contrary to the concept of resources (which is essentially a geological one), the notion of reserves designates the quantities that are technically and economically recoverable. Beyond the production-related effect, the reserves therefore evolve over time in accordance with numerous technical and economic parameters. Among these parameters, it can be seen that technical progress plays a considerable role throughout the process of converting resources into reserves, including progress in the identification, accessibility and processing of the resources, and improvements in economic viability. After having tackled the problem of measuring the 'technical progress effects' and citing examples, we demonstrate that the evolution in oil reserves is subject to three types of impact. These are a quantitative impact by significantly improving the recovery rates or making it possible to identify hitherto undetectable oil fields, a qualitative impact by widening the resource base thanks to the adoption of new categories of oil (in particular the so-called 'unconventional' oils) and by carrying out the gradual substitution between these resources of differing qualities. There is also a dynamic impact, through the acceleration of resource availability. Through these three approaches, technical progress makes makes it possible to ensure continuity in oil supply and contributes significantly to the recalculation of reserves. It therefore acts as a compensating factor, counterbalancing the progressive depletion of resources. (author)

Oxidative stress: development and progression of breast cancer:review article

Directory of Open Access Journals (Sweden)

Arash Salmaninejad

2017-04-01

Full Text Available Breast cancer is the most commonly diagnosed cancer in women worldwide. Enormous advancement has been made over the last decades in understanding the biology of breast cancer. Nevertheless, the molecular mechanisms regulating progression, gaining of invasive and metastatic phenotypes, and therapeutic resistance are still not completely understood. Oxidative stress initiate by disbalance in redox status of body. In this case, increase of free radicals in body cause tissue damage. One of the significant species of free radicals is reactive oxygen species (ROS that produced by various metabolic pathways, comprising aerobic metabolism in the mitochondrial respiratory chain. They play a serious role in cellular physiology and pathophysiology likewise beginning and evolution of numerous types of cancers. ROS overproduction is deleterious to cells, and considered key-factors for the development of numerous diseases, such as cardiovascular disorders, neurodegenerative diseases, and cancer. Cancer cells are commonly submitted to upper ROS levels that further incite malignant phenotype through motivation to preserved proliferation, angiogenesis, death evasion, invasiveness, and metastasis. ROS impress various signaling pathways, comprising mitogenic pathways and growth factors, and also controls numerous cellular processes, containing cell proliferation, thus stimulates the undisciplined growth of cells which inspires the development of tumors and initiates the progression of carcinogenesis. The importance of ROS on breast cancer development and etiology is being increasingly clarified. Nevertheless, fewer consideration has been given to the progress of redox system-targeted strategies for breast cancer treatment. Augmented oxidative stress caused by reactive species can diminish the body’s antioxidant defense against angiogenesis and metastasis in cancer cells. These processes are core factors in the development of cancer. Bimolecular reactions cause

Molecular Features of Subtype-Specific Progression from Ductal Carcinoma In Situ to Invasive Breast Cancer

Directory of Open Access Journals (Sweden)

Robert Lesurf

2016-07-01

Full Text Available Breast cancer consists of at least five main molecular “intrinsic” subtypes that are reflected in both pre-invasive and invasive disease. Although previous studies have suggested that many of the molecular features of invasive breast cancer are established early, it is unclear what mechanisms drive progression and whether the mechanisms of progression are dependent or independent of subtype. We have generated mRNA, miRNA, and DNA copy-number profiles from a total of 59 in situ lesions and 85 invasive tumors in order to comprehensively identify those genes, signaling pathways, processes, and cell types that are involved in breast cancer progression. Our work provides evidence that there are molecular features associated with disease progression that are unique to the intrinsic subtypes. We additionally establish subtype-specific signatures that are able to identify a small proportion of pre-invasive tumors with expression profiles that resemble invasive carcinoma, indicating a higher likelihood of future disease progression.

A Tissue Engineering Approach to Study the Progression of Breast Tumor Metastasis in Bone

National Research Council Canada - National Science Library

Che, Mingxin; Nie, Daotai

2005-01-01

Most patients dying of breast cancer suffer painful bone metastasis. It is our hypothesis that the invasive growth and progression of breast metastatic lesions in bone requires the participation of various constituents from "soil...

A Tissue Engineering Approach to Study the Progression of Breast Tumor Metastasis in Bone

National Research Council Canada - National Science Library

Che, Mingxin; Nie, Daotai

2006-01-01

Most patients dying of breast cancer suffer painful bone metastasis. It is our hypothesis that the invasive growth and progression of breast metastatic lesions in bone requires the participation of various constituents from "soil...

Technical progress by major task. Semiannual technical progress report, September 29, 1997 - March 29, 1998

International Nuclear Information System (INIS)

1998-01-01

The technical progress achieved during the period 29 September 1997 through 29 March 1998 on Contract DE-AC03-91SF18852 Radioisotope Thermoelectric Generators and Ancillary Activities is described in this report. The report is organized by program task structure: spacecraft integration and liaison; engineering support; safety; qualified unicouple production; RTG fabrication, assembly, and test; ground support equipment; RTG shipping and launch support; designs, reviews, and mission applications; project management, quality assurance, reliability, contract changes, CAGO acquisition (operating funds), and CAGO maintenance and repair

New Approaches for Early Detection of Breast Tumor Invasion or Progression

National Research Council Canada - National Science Library

Man, Yan-Gao

2003-01-01

To assess interactions between epithelial (EP) and myoepithelial (ME) cells in association with breast tumor progression and invasion, a double immunostaining technique with antibodies to smooth muscle actin (SMA...

Delineating an Epigenetic Continuum for Initiation, Transformation and Progression to Breast Cancer

Energy Technology Data Exchange (ETDEWEB)

Chen, Kang Mei; Stephen, Josena K. [Department of Otolaryngology/Head and Neck Surgery, Henry Ford Hospital, 1 Ford Place, 1D, Detroit, MI 48202 (United States); Raju, Usha [Department of Pathology, Henry Ford Hospital, Detroit, 1 Ford Place, 1D, Detroit, MI 48202 (United States); Worsham, Maria J., E-mail: mworsha1@hfhs.org [Department of Otolaryngology/Head and Neck Surgery, Henry Ford Hospital, 1 Ford Place, 1D, Detroit, MI 48202 (United States)

2011-03-29

Aberrant methylation of promoter CpG islands is a hallmark of human cancers and is an early event in carcinogenesis. We examined whether promoter hypermethylation contributes to the pathogenesis of benign breast lesions along a progression continuum to invasive breast cancer. The exploratory study cohort comprised 17 breast cancer patients with multiple benign and/or in situ lesions concurrently present with invasive carcinoma within a tumor biopsy. DNA from tumor tissue, normal breast epithelium when present, benign lesions (fibroadenoma, hyperplasia, papilloma, sclerosing adenosis, apocrine metaplasia, atypical lobular hyperplasia or atypical ductal hyperplasia), and in situ lesions of lobular carcinoma and ductal carcinoma were interrogated for promoter methylation status in 22 tumor suppressor genes using the multiplex ligation-dependent probe amplification assay (MS-MLPA). Methylation specific PCR was performed to confirm hypermethylation detected by MS-MLPA. Promoter methylation was detected in 11/22 tumor suppressor genes in 16/17 cases. Hypermethylation of RASSF1 was most frequent, present in 14/17 cases, followed by APC in 12/17, and GSTP1 in 9/17 cases with establishment of an epigenetic monocloncal progression continuum to invasive breast cancer. Hypermethylated promoter regions in normal breast epithelium, benign, and premalignant lesions within the same tumor biopsy implicate RASSF1, APC, GSTP1, TIMP3, CDKN2B, CDKN2A, ESR1, CDH13, RARB, CASP8, and TP73 as early events. DNA hypermethylation underlies the pathogenesis of step-wise transformation along a monoclonal continuum from normal to preneoplasia to invasive breast cancer.

Delineating an Epigenetic Continuum for Initiation, Transformation and Progression to Breast Cancer

International Nuclear Information System (INIS)

Chen, Kang Mei; Stephen, Josena K.; Raju, Usha; Worsham, Maria J.

2011-01-01

Aberrant methylation of promoter CpG islands is a hallmark of human cancers and is an early event in carcinogenesis. We examined whether promoter hypermethylation contributes to the pathogenesis of benign breast lesions along a progression continuum to invasive breast cancer. The exploratory study cohort comprised 17 breast cancer patients with multiple benign and/or in situ lesions concurrently present with invasive carcinoma within a tumor biopsy. DNA from tumor tissue, normal breast epithelium when present, benign lesions (fibroadenoma, hyperplasia, papilloma, sclerosing adenosis, apocrine metaplasia, atypical lobular hyperplasia or atypical ductal hyperplasia), and in situ lesions of lobular carcinoma and ductal carcinoma were interrogated for promoter methylation status in 22 tumor suppressor genes using the multiplex ligation-dependent probe amplification assay (MS-MLPA). Methylation specific PCR was performed to confirm hypermethylation detected by MS-MLPA. Promoter methylation was detected in 11/22 tumor suppressor genes in 16/17 cases. Hypermethylation of RASSF1 was most frequent, present in 14/17 cases, followed by APC in 12/17, and GSTP1 in 9/17 cases with establishment of an epigenetic monocloncal progression continuum to invasive breast cancer. Hypermethylated promoter regions in normal breast epithelium, benign, and premalignant lesions within the same tumor biopsy implicate RASSF1, APC, GSTP1, TIMP3, CDKN2B, CDKN2A, ESR1, CDH13, RARB, CASP8, and TP73 as early events. DNA hypermethylation underlies the pathogenesis of step-wise transformation along a monoclonal continuum from normal to preneoplasia to invasive breast cancer

Conjoint utility analysis of technical maturity and project progress of construction project

Directory of Open Access Journals (Sweden)

Ma Wei

2016-01-01

Full Text Available In this paper, taking construction project as the research object, the relationship between the project maturity index calculated by the construction project technical risks with different fine degree and the project progress index is studied, and the equilibrium relationship between the Party A’s utility curve and the Party B’s cost curve of using project maturity index and project progress index as the research variables is analyzed. The results show that, when the construction project technical risk division is more precise, the conjoint utility of the project's technical maturity index and the project progress is higher, and the project’s Party A and Party B two sides are closer to the optimal equilibrium. This shows that the construction project technical risk must be finely divided, and managed and controlled respectively, which will help to improve the conjoint utility of the project Party A and Party B two sides.

Cycling Towards Progress: Ribociclib, CDK 4/6 inhibitor for Breast Cancer.

Science.gov (United States)

Spring, Laura; Bardia, Aditya

2018-04-23

Ribociclib is an orally active, highly selective inhibitor of cyclin-dependent kinase (CDK) 4 and 6. It is the second CDK 4/6 inhibitor approved for hormone receptor-positive breast cancer. The addition of ribociclib to an aromatase inhibitor has resulted in marked improvements in progression-free survival for patients with metastatic breast cancer. Copyright ©2018, American Association for Cancer Research.

PTHrP drives breast tumor initiation, progression, and metastasis in mice and is a potential therapy target

Science.gov (United States)

Li, Jiarong; Karaplis, Andrew C.; Huang, Dao C.; Siegel, Peter M.; Camirand, Anne; Yang, Xian Fang; Muller, William J.; Kremer, Richard

2011-01-01

Parathyroid hormone–related protein (PTHrP) is a secreted factor expressed in almost all normal fetal and adult tissues. It is involved in a wide range of developmental and physiological processes, including serum calcium regulation. PTHrP is also associated with the progression of skeletal metastases, and its dysregulated expression in advanced cancers causes malignancy-associated hypercalcemia. Although PTHrP is frequently expressed by breast tumors and other solid cancers, its effects on tumor progression are unclear. Here, we demonstrate in mice pleiotropic involvement of PTHrP in key steps of breast cancer — it influences the initiation and progression of primary tumors and metastases. Pthrp ablation in the mammary epithelium of the PyMT-MMTV breast cancer mouse model caused a delay in primary tumor initiation, inhibited tumor progression, and reduced metastasis to distal sites. Mechanistically, it reduced expression of molecular markers of cell proliferation (Ki67) and angiogenesis (factor VIII), antiapoptotic factor Bcl-2, cell-cycle progression regulator cyclin D1, and survival factor AKT1. PTHrP also influenced expression of the adhesion factor CXCR4, and coexpression of PTHrP and CXCR4 was crucial for metastatic spread. Importantly, PTHrP-specific neutralizing antibodies slowed the progression and metastasis of human breast cancer xenografts. Our data identify what we believe to be new functions for PTHrP in several key steps of breast cancer and suggest that PTHrP may constitute a novel target for therapeutic intervention. PMID:22056386

The influence of HRT on technical recall in the UK Breast Screening Programme: are pain, compression force, and compressed breast thickness contributing factors?

International Nuclear Information System (INIS)

Nimmo, L.J.; Alston, L.A.C.; McFadyen, A.K.

2007-01-01

Aim: To investigate recall for technical reasons within the UK Breast Screening Programme, and to determine whether differences exist in those women using hormone replacement therapy (HRT), considering potential associations with reported pain, compression force used and compressed breast thickness (CBT) obtained. Materials and method: A prospective cohort study of 2765 women attending for incident round breast screening appointments who were either HRT users, with a minimum of 1 year duration (n = 1077), or had never used HRT (n = 1688). Data were collected using technical recall records, a radiographer data-collection sheet, and a self-administered participant questionnaire. Results: Sixty-eight (2.5%) participants were recalled for technical reasons of whom 28 (2.6%) were HRT and 40 (2.4%) non-HRT users. This difference was not statistically significant (p = 0.80). Significant differences were found for CBT between those HRT users who were and were not recalled for technical reasons (p < 0.01) and for the similar categories of non-HRT users (p = 0.03). No significant differences were found for force between those HRT users who were recalled or not (p = 0.73) and for the similar categories of non-HRT users (p = 0.07). Similarly no significant differences were found for pain between those HRT users who were recalled or not (p = 0.75) and for the similar categories of non-HRT users (p = 0.73). Conclusion: CBT was the only variable to have both a statistically and a clinically significant relationship with technical recall

International linear collider. A technical progress report

Energy Technology Data Exchange (ETDEWEB)

Arnold, Ned [Argonne National Laboratory, IL (United States); Aderhold, Sebastian [DESY, Hamburg (Germany); Adolphsen, Chris [Stanford Linear Accelerator Center, Menlo Park, CA (United States); and others

2012-07-01

The International Linear Collider: A Technical Progress Report marks the halfway point towards the Global Design Effort fulfilling its mandate to follow up the ILC Reference Design Report with a more optimised Technical Design Report (TDR) by the end of 2012. The TDR will be based on much of the work reported here and will contain all the elements needed to propose the ILC to collaborating governments, including a technical design and implementation plan that are realistic and have been better optimised for performance, cost and risk. We are on track to develop detailed plans for the ILC, such that once results from the Large Hadron Collider (LHC) at CERN establish the main science goals and parameters of the next machine, we will be in good position to make a strong proposal for this new major global project in particle physics. The two overriding issues for the ILC R and D programme are to demonstrate that the technical requirements for the accelerator are achievable with practical technologies, and that the ambitious physics goals can be addressed by realistic ILC detectors. This GDE interim report documents the impressive progress on the accelerator technologies that can make the ILC a reality. It highlights results of the technological demonstrations that are giving the community increased confidence that we will be ready to proceed with an ILC project following the TDR. The companion detector and physics report document likewise demonstrates how detector designs can meet the ambitious and detailed physics goals set out by the ILC Steering Committee. LHC results will likely affect the requirements for the machine design and the detectors, and we are monitoring that very closely, intending to adapt our design as those results become available.

International Linear Collider-A Technical Progress Report

Energy Technology Data Exchange (ETDEWEB)

Elsen, Eckhard; /DESY; Harrison, Mike; /Brookhaven; Hesla, Leah; /Fermilab; Ross, Marc; /Fermilab; Royole-Degieux, Perrine; /Paris, IN2P3; Takahashi, Rika; /KEK, Tsukuba; Walker, Nicholas; /DESY; Warmbein, Barbara; /DESY; Yamamoto, Akira; /KEK, Tsukuba; Yokoya, Kaoru; /KEK, Tsukuba; Zhang, Min; /Beijing, Inst. High Energy Phys.

2011-11-04

The International Linear Collider: A Technical Progress Report marks the halfway point towards the Global Design Effort fulfilling its mandate to follow up the ILC Reference Design Report with a more optimised Technical Design Report (TDR) by the end of 2012. The TDR will be based on much of the work reported here and will contain all the elements needed to propose the ILC to collaborating governments, including a technical design and implementation plan that are realistic and have been better optimised for performance, cost and risk. We are on track to develop detailed plans for the ILC, such that once results from the Large Hadron Collider (LHC) at CERN establish the main science goals and parameters of the next machine, we will be in good position to make a strong proposal for this new major global project in particle physics. The two overriding issues for the ILC R&D programme are to demonstrate that the technical requirements for the accelerator are achievable with practical technologies, and that the ambitious physics goals can be addressed by realistic ILC detectors. This GDE interim report documents the impressive progress on the accelerator technologies that can make the ILC a reality. It highlights results of the technological demonstrations that are giving the community increased confidence that we will be ready to proceed with an ILC project following the TDR. The companion detector and physics report document likewise demonstrates how detector designs can meet the ambitious and detailed physics goals set out by the ILC Steering Committee. LHC results will likely affect the requirements for the machine design and the detectors, and we are monitoring that very closely, intending to adapt our design as those results become available.

Technical progress in planning organization of the Ostravo-Karwina coal basin, ''Mining Projects of Ostravo''

Energy Technology Data Exchange (ETDEWEB)

Karpeta, B; Kolar, J

1979-01-01

Based on the main task of further improvement in labor productivity and improvement in the quality of products, the leading planning organization of the Ostravo-Karwina basin is planning and realizing progressive technological plans based on new equipment. Long-term plans for basin development up to 1990 stipulate a rise in capital investments by 180%, increase in the volume of productivity by 164% with a rise in the number of workers by 142%. Corresponding technical progress in planning is based on an improvement in the system of scientific-technical information, automation and technical equipping of the planning process, improvements in the forms and organizational structure. Organization of specialized research-planning groups to substantiate and to technically-economically evaluate technical progress, and also to develop comprehensive technical assignments is stipulated.

Swallowable Wireless Capsule Endoscopy: Progress and Technical Challenges

Directory of Open Access Journals (Sweden)

Guobing Pan

2012-01-01

Full Text Available Wireless capsule endoscopy (WCE offers a feasible noninvasive way to detect the whole gastrointestinal (GI tract and revolutionizes the diagnosis technology. However, compared with wired endoscopies, the limited working time, the low frame rate, and the low image resolution limit the wider application. The progress of this new technology is reviewed in this paper, and the evolution tendencies are analyzed to be high image resolution, high frame rate, and long working time. Unfortunately, the power supply of capsule endoscope (CE is the bottleneck. Wireless power transmission (WPT is the promising solution to this problem, but is also the technical challenge. Active CE is another tendency and will be the next geneion of the WCE. Nevertheless, it will not come true shortly, unless the practical locomotion mechanism of the active CE in GI tract is achieved. The locomotion mechanism is the other technical challenge, besides the challenge of WPT. The progress about the WPT and the active capsule technology is reviewed.

Stockholm international conference 2003 on geological repositories: Political and technical progress

International Nuclear Information System (INIS)

2004-01-01

The conference reviewed global progress made as well as current perspectives on the activities to develop geologic repositories. The objectives were to review the progress in policy making as well as technical issues and to strengthen international co-operation on waste management and disposal issues. The first day of the conference addressed the policy aspects of geological repositories and the second day featured the more technical issues. Session 1: International progress in performing long-term safety studies and security of geological disposal were discussed and reviewed with examples from OECD/NEA, Belgium, Sweden, USA, Switzerland and Russia. Session 2: Views on stakeholder involvement and decision making process were presented by international organisations and national implementers from Japan, United Kingdom, Belgium and OECD/NEA. Session 3: Views on stakeholder involvement and decision making process were presented by regional and local stakeholders from France, Finland, Korea and Sweden. Session 4: International instruments assisting in the implementation of geological repositories were discussed, for example ICRP and IAEA/NEA safety documents, Joint Convention, Safeguard agreements, Nuclear Liability Conventions, etc. Session 5: The contribution of Research, Development and Demonstration was discussed with overviews of the progress achieved on scientific and technical issues over the past four years. Progress and key issues were presented from Switzerland, USA, Finland, Japan, Sweden and IAEA. Each of the papers and poster presentations have been analysed and indexed separately

Technical progress safeguards future. Technischer Fortschritt sichert die Zukunft

Energy Technology Data Exchange (ETDEWEB)

1985-01-01

'Technical progress safeguards future', the guiding theme of the 1985 conference of German engineers, calls for discussion. In five lectures representatives of the subdivisions of 'VDI' issued their statements from the viewpoints of their special fields. These lectures were completed by reports on the part of the remaining VDI subdivisions, which are published together with the lectures in this volume. The complex guiding theme is meant to stimulate discussion, which should be conducted also with representatives of other sciences and the public. The volume contains a.o. contributions regarding future prospects, given certain modifications in construction engineering and user behaviour in the sector heating and air-conditioning, regarding the development of new construction techniques to protect the environment, and regarding clean air as an international concern of engineers. For these three contributions separate entries were made. Other presentations relate to: automobile production technology; energy supply as an engineering task; information, invention, innovation as stages of technical progress; progress in materials technology; noise of motor vehicles - current state and future prospects. (orig./HSCH).

An atypical cause of rapidly progressing breast lump with abscess formation: Pure squamous cell carcinoma of the breast.

Science.gov (United States)

Cilekar, Murat; Erkasap, Serdar; Oner, Ulku; Akici, Murat; Ciftci, Evrim; Dizen, Hayrettin; Turel, Serkan; Kavak, Ozgu I; Yilmaz, Sezgin

2015-01-01

Squamous cell carcinoma (SCC) is a rare type of breast malignancy and little is known about long-term outcome. In the present report, the clinical features, histopathologic findings and postoperative course of a patient with squamous cell carcinoma are described. We have treated a 47-years-old woman who admitted for right breast mass without any discharge, bleeding and pain. The tumor was, 3 × 2 × 1.5 cm in size with central abscess formation. The result of surgical biopsy revealed large cell keratinizing type of SCC. The metastatic work-up studies ruled out any other probable sources of primary tumor. The patient was performed modified radical mastectomy and axillary dissection and received two cycles of chemotherapy. Squamous cell carcinoma of the breast (SCCB) is a rare entity and should be considered in patients with rapidly progressing breast mass. It should also be considered in breast lesions with abscess formation. The initial therapeutic approach should be surgical excision after histopathological diagnosis.

Postmenopausal obesity promotes tumor angiogenesis and breast cancer progression in mice.

Science.gov (United States)

Gu, Jian-Wei; Young, Emily; Patterson, Sharla G; Makey, Kristina L; Wells, Jeremy; Huang, Min; Tucker, Kevan B; Miele, Lucio

2011-05-15

Obese postmenopausal women have a 50% higher risk of breast cancer than non-obese women. There is not an animal model that mimics postmenopausal obesity related to breast cancer progression. Using age-relevant C57BL/6 mice, this study determined whether postmenopausal obesity increases VEGF expression, tumor angiogenesis, and breast tumor growth. Ovariectomy (OVX) was performed in 12 sixty week-old female mice, then followed by a low-fat (5%, LF, n=6) or a high-fat (60%, HF, n=6) diet for 12 weeks. In the eighth week of the dietary program, 10(6) E0771 (mouse breast cancer) cells were injected in the left fourth mammary gland. Tumor size was monitored for 4 weeks. Body weights were monitored weekly. At the end of the experiment, blood samples, visceral fat and tumors were collected for measuring VEGF expression using ELISA and intratumoral microvessel density (IMD) using CD31 immunochemistry. Body weight was significantly increased in OVX/HF mice, compared to OVX/LF group (55.3±1.7 vs. 41.5±1.5 g; p < 0.01). There was a two-fold increase in the ratio of visceral fat/BW in OVX/HF mice, compared to those in OVX/LF group (0.062±0.005 vs. 0.032±0.003; p < 0.01). Postmenopausal obesity significantly increased breast tumor weight over the control (4.62±0.63 vs. 1.98±0.27 g; p < 0.01) and IMD (173±3.7 vs. 139±4.3 IM#/mm^2; p < 0.01). Tumor VEGF levels were higher in OVX/HF mice, compared to OVX/LF group (73.3±3.8 vs. 49.5±4.3 pg/mg protein; p < 0.01). Plasma VEGF levels (69±7.1 vs. 48±3.5 pg/ml) and visceral fat VEGF levels (424.4±39.5 vs. 208.5±22.4 pg/mg protein) were significantly increased in OVX/HF mice, compared to OVX/LF group, respectively (n=6; p < 0.01). Interestingly, adipose tissue primary culture showed that subcutaneous fat released more VEGF, compared to visceral fat (6.77±1.14 vs. 0.94±0.16 pg/mg tissue; n=6; p < 0.01). These findings support the hypothesis that postmenopausal obesity promotes tumor angiogenesis and breast cancer

The role of S100 genes in breast cancer progression.

LENUS (Irish Health Repository)

McKiernan, Eadaoin

2012-02-01

The S100 gene family encode low molecular weight proteins implicated in cancer progression. In this study, we analyzed the expression of four S100 genes in one cohort of patients with breast cancer and 16 S100 genes in a second cohort. In both cohorts, the expression of S100A8 and S1009 mRNA level was elevated in high-grade compared to low-grade tumors and in estrogen receptor-negative compared to estrogen receptor-positive tumors. None of the S100 transcripts investigated were significantly associated with the presence of lymph node metastasis. Notably, multiple S100 genes, including S100A1, S100A2, S100A4, S100A6, S100A8, S100A9, S100A10, S100A11, and S100A14 were upregulated in basal-type breast cancers compared to non-basal types. Using Spearman\\'s correlation analysis, several S100 transcripts correlated significantly with each other, the strongest correlation has been found between S100A8 and S100A9 (r = 0.889, P < 0.001, n = 295). Of the 16 S100 transcripts investigated, only S100A11 and S100A14 were significantly associated with patient outcome. Indeed, these two transcripts predicted outcome in the cohort of patients that did not receive systemic adjuvant therapy. Based on our findings, we conclude that the different S100 genes play varying roles in breast cancer progression. Specific S100 genes are potential targets for the treatment of basal-type breast cancers.

The role of S100 genes in breast cancer progression.

LENUS (Irish Health Repository)

McKiernan, Eadaoin

2011-06-01

The S100 gene family encode low molecular weight proteins implicated in cancer progression. In this study, we analyzed the expression of four S100 genes in one cohort of patients with breast cancer and 16 S100 genes in a second cohort. In both cohorts, the expression of S100A8 and S1009 mRNA level was elevated in high-grade compared to low-grade tumors and in estrogen receptor-negative compared to estrogen receptor-positive tumors. None of the S100 transcripts investigated were significantly associated with the presence of lymph node metastasis. Notably, multiple S100 genes, including S100A1, S100A2, S100A4, S100A6, S100A8, S100A9, S100A10, S100A11, and S100A14 were upregulated in basal-type breast cancers compared to non-basal types. Using Spearman\\'s correlation analysis, several S100 transcripts correlated significantly with each other, the strongest correlation has been found between S100A8 and S100A9 (r = 0.889, P < 0.001, n = 295). Of the 16 S100 transcripts investigated, only S100A11 and S100A14 were significantly associated with patient outcome. Indeed, these two transcripts predicted outcome in the cohort of patients that did not receive systemic adjuvant therapy. Based on our findings, we conclude that the different S100 genes play varying roles in breast cancer progression. Specific S100 genes are potential targets for the treatment of basal-type breast cancers.

Tristetraprolin: A novel target of diallyl disulfide that inhibits the progression of breast cancer.

Science.gov (United States)

Xiong, Ting; Liu, Xiao-Wang; Huang, Xue-Long; Xu, Xiong-Feng; Xie, Wei-Quan; Zhang, Su-Jun; Tu, Jian

2018-05-01

Diallyl disulfide (DADS), a volatile component of garlic oil, has various biological properties, including antioxidant, antiangiogenic and anticancer effects. The present study aimed to explore novel targets of DADS that may slow or stop the progression of breast cancer. First, xenograft tumor models were created by subcutaneously injecting MCF-7 and MDA-MB-231 breast cancer cells into nude mice. Subsequently, western blot analysis was performed to investigate the expression of tristetraprolin (TTP), urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9) in the xenograft tumors, and cell cultures. Tablet cloning, Transwell and wound healing assays revealed that DADS treatment significantly inhibited the proliferation, invasion and migration of breast cancer cells. In addition, DADS treatment led to significant downregulation of uPA and MMP-9 protein expression, but significantly upregulated TTP expression in vivo and in vitro . Knocking down TTP expression using small interfering RNA reversed the aforementioned effects of DADS, which suggests TTP is a key target of DADS in inhibiting the progression of breast cancer.

Expression of Notch1 Correlates with Breast Cancer Progression and Prognosis.

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Xun Yuan

Full Text Available Various studies have evaluated the significance of Notch1 expression in breast cancer, but the results have ever been disputed. By using 21 studies involving 3867 patients, this meta-analysis revealed that the expression of Notch1 was significantly higher in breast cancer than in normal tissues (OR=7.21; 95%CI, 4.7-11.07 and that higher Notch1 expression was associated with transition from ductal carcinoma in situ (DCIS to invasive cancer (OR=3.75; 95% CI, 1.8-7.78. Higher Notch1 activity was observed in the basal subtype of breast cancer (OR=2.53; 95% CI, 1.18-5.43. Moreover, patients with Notch1 overexpression exhibited significantly worse overall and recurrence-free survival. Our meta-analysis suggests that Notch inhibitors may be useful in blocking the early progression of DCIS and that the outcomes of clinical trials for Notch1-targeting therapeutics could be improved by the molecular stratification of breast cancer patients.

The pioneer factor PBX1 is a novel driver of metastatic progression in ERα-positive breast cancer

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Magnani, Luca; Patten, Darren K.; Nguyen, Van T.M.; Hong, Sung-Pil; Steel, Jennifer H.; Patel, Naina; Lombardo, Ylenia; Faronato, Monica; Gomes, Ana R.; Woodley, Laura; Page, Karen; Guttery, David; Primrose, Lindsay; Garcia, Daniel Fernandez; Shaw, Jacqui; Viola, Patrizia; Green, Andrew; Nolan, Christopher; Ellis, Ian O.; Rakha, Emad A.; Shousha, Sami; Lam, Eric W.-F.; Győrffy, Balázs; Lupien, Mathieu; Coombes, R. Charles

2015-01-01

Over 30% of ERα breast cancer patients develop relapses and progress to metastatic disease despite treatment with endocrine therapies. The pioneer factor PBX1 translates epigenetic cues and mediates estrogen induced ERα binding. Here we demonstrate that PBX1 plays a central role in regulating the ERα transcriptional response to epidermal growth factor (EGF) signaling. PBX1 regulates a subset of EGF-ERα genes highly expressed in aggressive breast tumours. Retrospective stratification of luminal patients using PBX1 protein levels in primary cancer further demonstrates that elevated PBX1 protein levels correlate with earlier metastatic progression. In agreement, PBX1 protein levels are significantly upregulated during metastatic progression in ERα-positive breast cancer patients. Finally we reveal that PBX1 upregulation in aggressive tumours is partly mediated by genomic amplification of the PBX1 locus. Correspondingly, ERα-positive breast cancer patients carrying PBX1 amplification are characterized by poor survival. Notably, we demonstrate that PBX1 amplification can be identified in tumor derived-circulating free DNA of ERα-positive metastatic patients. Metastatic patients with PBX1 amplification are also characterized by shorter relapse-free survival. Our data identifies PBX1 amplification as a functional hallmark of aggressive ERα-positive breast cancers. Mechanistically, PBX1 amplification impinges on several critical pathways associated with aggressive ERα-positive breast cancer. PMID:26215677

ADAM12 produced by tumor cells rather than stromal cells accelerates breast tumor progression

DEFF Research Database (Denmark)

Frohlich, Camilla; Nehammer, Camilla; Albrechtsen, Reidar

2011-01-01

that ADAM12 deficiency reduces breast tumor progression in the PyMT model. However, the catalytic activity of ADAM12 appears to be dispensable for its tumor-promoting effect. Interestingly, we demonstrate that ADAM12 endogenously expressed in tumor-associated stroma in the PyMT model does not influence......Expression of ADAM12 is low in most normal tissues, but is markedly increased in numerous human cancers, including breast carcinomas. We have previously shown that overexpression of ADAM12 accelerates tumor progression in a mouse model of breast cancer (PyMT). In the present study, we found...... hypothesized, however, that the tumor-associated stroma may stimulate ADAM12 expression in tumor cells, based on the fact that TGF-ß1 stimulates ADAM12 expression and is a well-known growth factor released from tumor-associated stroma. TGF-ß1 stimulation of ADAM12-negative Lewis lung tumor cells induced ADAM12...

An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models.

LENUS (Irish Health Repository)

Donatello, Simona

2011-01-01

Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression.

α2-adrenergic blockade mimics the enhancing effect of chronic stress on breast cancer progression

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Lamkin, Donald M.; Sung, Ha Yeon; Yang, Gyu Sik; David, John M.; Ma, Jeffrey C.Y.; Cole, Steve W.; Sloan, Erica K.

2014-01-01

Experimental studies in preclinical mouse models of breast cancer have shown that chronic restraint stress can enhance disease progression by increasing catecholamine levels and subsequent signaling of β-adrenergic receptors. Catecholamines also signal α-adrenergic receptors, and greater α-adrenergic signaling has been shown to promote breast cancer in vitro and in vivo. However, antagonism of α-adrenergic receptors can result in elevated catecholamine levels, which may increase β-adrenergic signaling, because pre-synaptic α2-adrenergic receptors mediate an autoinhibition of sympathetic transmission. Given these findings, we examined the effect of α-adrenergic blockade on breast cancer progression under non-stress and stress conditions (chronic restraint) in an orthotopic mouse model with MDA-MB-231HM cells. Chronic restraint increased primary tumor growth and metastasis to distant tissues as expected, and non-selective α-adrenergic blockade by phentolamine significantly inhibited those effects. However, under non-stress conditions, phentolamine increased primary tumor size and distant metastasis. Sympatho-neural gene expression for catecholamine biosynthesis enzymes was elevated by phentolamine under non-stress conditions, and the non-selective β-blocker propranolol inhibited the effect of phentolamine on breast cancer progression. Selective α2-adrenergic blockade by efaroxan also increased primary tumor size and distant metastasis under non-stress conditions, but selective α1-adrenergic blockade by prazosin did not. These results are consistent with the hypothesis that α2-adrenergic signaling can act through an autoreceptor mechanism to inhibit sympathetic catecholamine release and, thus, modulate established effects of β-adrenergic signaling on tumor progression-relevant biology. PMID:25462899

FoxD3 deficiency promotes breast cancer progression by induction of epithelial–mesenchymal transition

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Chu, Tian-Li [Department of General Surgery, The People’s Hospital of Wuqing, Tianjin (China); Zhao, Hong-Meng [Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Li, Yue [Department of Respiration, Affiliated Hospital of Medical College of Chinese People’s Armed Police Force, Tianjin (China); Chen, Ao-Xiang; Sun, Xuan [Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Ge, Jie, E-mail: gejie198003@163.com [Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China)

2014-04-04

Highlights: • FOXD3 is down-regulated in breast cancer tissues. • FOXD3 inhibits breast cancer cell proliferation and invasion. • FoxD3 deficiency induces epithelial–mesenchymal transition. - Abstract: The transcription factor forkhead box D3 (FOXD3) plays an important role in the development of neural crest and gastric cancer cells. However, the function and mechanisms of FOXD3 in the breast tumorigenesis and progression is still limited. Here, we report that FOXD3 is a tumor suppressor of breast cancer tumorigenicity and aggressiveness. We found that FOXD3 is down-regulated in breast cancer tissues. Patients with low FOXD3 expression have a poor outcome. Depletion of FOXD3 expression promotes breast cancer cell proliferation and invasion in vitro, whereas overexpression of FOXD3 inhibits breast cancer cell proliferation and invasion both in vitro and in vivo. In addition, depletion of FOXD3 is linked to epithelial–mesenchymal transition (EMT)-like phenotype. Our results indicate FOXD3 exhibits tumor suppressive activity and may be useful for breast therapy.

FoxD3 deficiency promotes breast cancer progression by induction of epithelial–mesenchymal transition

International Nuclear Information System (INIS)

Chu, Tian-Li; Zhao, Hong-Meng; Li, Yue; Chen, Ao-Xiang; Sun, Xuan; Ge, Jie

2014-01-01

Highlights: • FOXD3 is down-regulated in breast cancer tissues. • FOXD3 inhibits breast cancer cell proliferation and invasion. • FoxD3 deficiency induces epithelial–mesenchymal transition. - Abstract: The transcription factor forkhead box D3 (FOXD3) plays an important role in the development of neural crest and gastric cancer cells. However, the function and mechanisms of FOXD3 in the breast tumorigenesis and progression is still limited. Here, we report that FOXD3 is a tumor suppressor of breast cancer tumorigenicity and aggressiveness. We found that FOXD3 is down-regulated in breast cancer tissues. Patients with low FOXD3 expression have a poor outcome. Depletion of FOXD3 expression promotes breast cancer cell proliferation and invasion in vitro, whereas overexpression of FOXD3 inhibits breast cancer cell proliferation and invasion both in vitro and in vivo. In addition, depletion of FOXD3 is linked to epithelial–mesenchymal transition (EMT)-like phenotype. Our results indicate FOXD3 exhibits tumor suppressive activity and may be useful for breast therapy

Effects of clusterin over-expression on metastatic progression and therapy in breast cancer

International Nuclear Information System (INIS)

Flanagan, Louise; Whyte, Lorna; Chatterjee, Namita; Tenniswood, Martin

2010-01-01

Clusterin is a secreted glycoprotein that is upregulated in a variety of cell lines in response to stress, and enhances cell survival. A second nuclear isoform of clusterin that is associated with cell death has also been identified. The aim of this study was to determine the role(s) of the secretory isoform in breast tumor progression and metastasis. To investigate the role of secretory clusterin in the biology of breast cancer tumor growth and resistance to therapy we have engineered an MCF-7 cell line (MCF-7CLU) that over-expresses clusterin. We have measured the in vitro effects of clusterin over-expression on cell cycle, cell death, and sensitivity to TNFalpha and tamoxifen. Using an orthotopic model of breast cancer, we have also determined the effects of over-expression of clusterin on tumor growth and metastatic progression. In vitro, over-expression of secretory clusterin alters the cell cycle kinetics and decreases the rate of cell death, resulting in the enhancement of cell growth. Over-expression of secretory clusterin also blocks the TNFalpha-mediated induction of p21 and abrogates the cleavage of Bax to t-Bax, rendering the MCF-7CLU cells significantly more resistant to the cytokine than the parental cells. Orthotopic primary tumors derived from MCF-7CLU cells grow significantly more rapidly than tumors derived from parental MCF-7 cells and, unlike the parental cells, metastasize frequently to the lungs. These data suggest that secretory clusterin, which is frequently up-regulated in breast cancers by common therapies, including anti-estrogens, may play a significant role in tumor growth, metastatic progression and subsequent drug resistance in surviving cells

Overexpression of prostate tumor overexpressed 1 correlates with tumor progression and predicts poor prognosis in breast cancer

International Nuclear Information System (INIS)

Lei, Fangyong; Zhang, Longjuan; Li, Xinghua; Lin, Xi; Wu, Shu; Li, Fengyan; Liu, Junling

2014-01-01

Prostate tumor overexpressed 1 (PTOV1) was demonstrated to play an important role in cancer progression and was correlated with unfavorable clinical outcome. However, the clinical role of PTOV1 in cancer remains largely unknown. This study aimed to investigate the expression and clinicopathological significance of PTOV1 in breast cancer. The mRNA and protein expression levels of PTOV1 were analyzed in 12 breast cancer cell lines and eight paired breast cancer tumors by semi-quantitative real time-PCR and western blotting, respectively. Immunohistochemistry was performed to assess PTOV1 protein expression in 169 paraffin-embedded, archived breast cancer samples. Survival analysis and Cox regression analysis were performed to investigate the clinicopathological significance of PTOV1 expression. Our data revealed that PTOV1 was frequently overexpressed in breast cancer cell lines compared to normal human breast epithelial cells and in primary breast cancer samples compared to adjacent noncancerous breast tissues, at both the mRNA and protein levels. Moreover, high expression of PTOV1 in breast cancer is strongly associated with clinicopathological characteristics and estrogen receptor expression status (P = 0.003). Breast cancer patients with higher PTOV1 expression had substantially shorter survival times than patients with lower PTOV1 expression (P < 0.001). Univariate and multivariate analysis revealed that PTOV1 might be an independent prognostic factor for breast cancer patients (P = 0.005). Our study showed that PTOV1 is upregulated in breast cancer cell lines and clinical samples, and its expression was positively associated with progression and aggressiveness of breast cancer, suggesting that PTOV1 could serve as an independent prognostic marker

Technical Progress of the New Worlds Observer Mission

Science.gov (United States)

Lo, Amy; Noecker, C.; Cash, W.; NWO Study Team

2009-01-01

We report on the technical progress of the New Worlds Observer (NWO) mission concept. NWO is a two spacecraft mission that is capable of detecting and characterizing extra-solar, terrestrial planets and planetary systems. NWO consists of an external starshade and an UV-optical space telescope, flying in tandem. The starshade is a petal-shaped, opaque screen that creates an extremely dark shadow large enough to shade the telescope aperture from the target star. The NWO team has been addressing the top technology challenges of the concept, and report here our progress. We will present the current mission configuration best suited to address Terrestrial Planet Finding requirements, and highlight the technological breakthroughs that we have achieved this year. In particular, we will report on progress made in precision deployables for the large starshade, and the trajectory & alignment control system for NWO. We will also briefly highlight advances in understanding the starshade optical performance.

Effects of clusterin over-expression on metastatic progression and therapy in breast cancer

Directory of Open Access Journals (Sweden)

Chatterjee Namita

2010-03-01

Full Text Available Abstract Background Clusterin is a secreted glycoprotein that is upregulated in a variety of cell lines in response to stress, and enhances cell survival. A second nuclear isoform of clusterin that is associated with cell death has also been identified. The aim of this study was to determine the role(s of the secretory isoform in breast tumor progression and metastasis. Methods To investigate the role of secretory clusterin in the biology of breast cancer tumor growth and resistance to therapy we have engineered an MCF-7 cell line (MCF-7CLU that over-expresses clusterin. We have measured the in vitro effects of clusterin over-expression on cell cycle, cell death, and sensitivity to TNFalpha and tamoxifen. Using an orthotopic model of breast cancer, we have also determined the effects of over-expression of clusterin on tumor growth and metastatic progression. Results In vitro, over-expression of secretory clusterin alters the cell cycle kinetics and decreases the rate of cell death, resulting in the enhancement of cell growth. Over-expression of secretory clusterin also blocks the TNFalpha-mediated induction of p21 and abrogates the cleavage of Bax to t-Bax, rendering the MCF-7CLU cells significantly more resistant to the cytokine than the parental cells. Orthotopic primary tumors derived from MCF-7CLU cells grow significantly more rapidly than tumors derived from parental MCF-7 cells and, unlike the parental cells, metastasize frequently to the lungs. Conclusions These data suggest that secretory clusterin, which is frequently up-regulated in breast cancers by common therapies, including anti-estrogens, may play a significant role in tumor growth, metastatic progression and subsequent drug resistance in surviving cells.

Rrp1b, a new candidate susceptibility gene for breast cancer progression and metastasis.

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Nigel P S Crawford

2007-11-01

Full Text Available A novel candidate metastasis modifier, ribosomal RNA processing 1 homolog B (Rrp1b, was identified through two independent approaches. First, yeast two-hybrid, immunoprecipitation, and functional assays demonstrated a physical and functional interaction between Rrp1b and the previous identified metastasis modifier Sipa1. In parallel, using mouse and human metastasis gene expression data it was observed that extracellular matrix (ECM genes are common components of metastasis predictive signatures, suggesting that ECM genes are either important markers or causal factors in metastasis. To investigate the relationship between ECM genes and poor prognosis in breast cancer, expression quantitative trait locus analysis of polyoma middle-T transgene-induced mammary tumor was performed. ECM gene expression was found to be consistently associated with Rrp1b expression. In vitro expression of Rrp1b significantly altered ECM gene expression, tumor growth, and dissemination in metastasis assays. Furthermore, a gene signature induced by ectopic expression of Rrp1b in tumor cells predicted survival in a human breast cancer gene expression dataset. Finally, constitutional polymorphism within RRP1B was found to be significantly associated with tumor progression in two independent breast cancer cohorts. These data suggest that RRP1B may be a novel susceptibility gene for breast cancer progression and metastasis.

Technical progress faced with the challenges of the energy sector in the future

International Nuclear Information System (INIS)

Maillard, D.

1999-01-01

The colloquium organised by the Association of Energy Economists dealing with the theme 'Technical progress faced with the challenges of the energy sector in the future' takes place against a backdrop of ever-increasing initiatives in this field, for example at the World Energy Council or the International Energy Agency Faith in technical progress is widespread but should be supported by studies without any preconceived ideas. Research and development efforts must be fully supported, and in a climate of opening markets and liberalization the public authorities have a major role to pay. Historically, the markets have always been able to meet new needs thanks to technology, but the ambitious targets that the international community has set itself regarding the emission of greenhouse gases imply technical improvements and major investments. (authors)

Breast Carcinoma Progression and Tumour Vascular Markers Related to Apoptotic Mechanisms

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Miroslava Bilecova-Rabajdova

2014-01-01

Full Text Available Background. In the last few years, the cancer research had tried to identify and characterize new biochemical and molecular pathways in which the inhibition induces prosurvival mechanisms. Our work describes the expression of two different members of apoptotic regulatory pathway and their relationship with a progression of breast carcinoma. Materials and Methods. We compared expression of genes related to apoptosis (DR6 and Gpm6B in the blood of patients suffering from stage I of breast cancer in different grades (I–IV, with healthy controls. After isolation of mRNA, transcription of mRNA into the cDNA was performed. The quantification of gene expression changes in DR6 and Gpm6B was detected by RT-PCR method. Analysis at the protein level was performed by the Western blot.Results. In statistical analysis of Dr6 mRNA level changes we detected significant increase starting in Grading 1 (G1 and reached maximal level in G3.This expression on mRNA levels was similar to protein levels, which copy rising tendency with maximal value in G3. The results of Gpm6B were significantly lower.Conclusion. This result showed that antiapoptotic signalling during neovascularization is increased significantly. It would be advisable in the future to study the influence of cytostatic treatment on the expression of genes related to apoptotic pathways and their relationship with progression of breast cancer tumours.

Potential Biomarker of L type Amino Acid Transporter 1 in Breast Cancer Progression

International Nuclear Information System (INIS)

Liang, Zhongxing; Cho, Heidi T.; Williams, Larry; Zhu, Aizhi; Liang, Ke; Huang, Ke; Wu, Hui; Jiang, Chunsu; Hong, Samuel; Crowe, Ronald; Goodman, Mark M.; Shim, Hyunsuk

2011-01-01

L type amino acid transporter 1 (LAT1) is essential for the transport of large neutral amino acids. However, its role in breast cancer growth remains largely unknown. The purpose of the study is to investigate whether LAT1 is a potential biomarker for the diagnosis and treatment of breast cancer. LAT1 mRNA and protein levels in breast cancer cell lines and tissues were analyzed. In addition, the effects of targeting LAT1 for the inhibition of breast cancer cell tumorigenesis were assessed with soft agar assay. The imaging of xenograft with 1 amino 3 [ 18F ]fluorocyclo butane 1 carboxylic acid ([ 18F ]FACBC) PET was assessed for its diagnostic biomarker potential. Normal breast tissue or low malignant cell lines expressed low levels of LAT1 mRNA and protein, while highly malignant cancer cell lines and high grade breast cancer tissue expressed high levels of LAT1. In addition, higher expression levels of LAT1 in breast cancer tissues were consistent with advanced stage breast cancer. Furtermore, the blockade of LAT1 with its inhibitor, 2 amino bicyclo[2.2.1]heptane 2 carboxylic acid (BCH), or the knockdown of LAT1 with siRNA, inhibited proliferation and tumorigenesis of breast cancer cells. A leucine analog, [ 18F ]FACBC, has been demonstrated to be an excellent PET tracer for the non invasive imaging og malignant breast cancer using an orthotopic animal model. The overexpression of LAT1 is required for the progression of breast cancer. LAT1 represents a potential biomarker for therapy and diagnosis of breast cancer. [ 18F ]FACBC that correlates with LAT1 function is a potential PET tracer for malignant breast tumor imaging

Progressive strength training to prevent LYmphoedema in the first year after breast CAncer

DEFF Research Database (Denmark)

Ammitzbøll, Gunn; Lanng, Charlotte; Kroman, Niels

2017-01-01

BACKGROUND: Lymphoedema is a common late effect after breast cancer (BC) that has no effective cure once chronic. Accumulating evidence supports progressive strength training (PRT) as a safe exercise modality in relation to the onset and exacerbation of lymphoedema. In the 'preventive intervention...... against LYmphoedema after breast CAncer' (LYCA) feasibility study we examined the feasibility of a program of PRT in the first year after BC to inform a planned randomised controlled trial (RCT). MATERIAL AND METHODS: LYCA was a one-group prospective pilot trial inviting women operated with axillary lymph...

Joint modelling of longitudinal CEA tumour marker progression and survival data on breast cancer

Science.gov (United States)

Borges, Ana; Sousa, Inês; Castro, Luis

2017-06-01

This work proposes the use of Biostatistics methods to study breast cancer in patients of Braga's Hospital Senology Unit, located in Portugal. The primary motivation is to contribute to the understanding of the progression of breast cancer, within the Portuguese population, using a more complex statistical model assumptions than the traditional analysis that take into account a possible existence of a serial correlation structure within a same subject observations. We aim to infer which risk factors aect the survival of Braga's Hospital patients, diagnosed with breast tumour. Whilst analysing risk factors that aect a tumour markers used on the surveillance of disease progression the Carcinoembryonic antigen (CEA). As survival and longitudinal processes may be associated, it is important to model these two processes together. Hence, a joint modelling of these two processes to infer on the association of these was conducted. A data set of 540 patients, along with 50 variables, was collected from medical records of the Hospital. A joint model approach was used to analyse these data. Two dierent joint models were applied to the same data set, with dierent parameterizations which give dierent interpretations to model parameters. These were used by convenience as the ones implemented in R software. Results from the two models were compared. Results from joint models, showed that the longitudinal CEA values were signicantly associated with the survival probability of these patients. A comparison between parameter estimates obtained in this analysis and previous independent survival[4] and longitudinal analysis[5][6], lead us to conclude that independent analysis brings up bias parameter estimates. Hence, an assumption of association between the two processes in a joint model of breast cancer data is necessary. Results indicate that the longitudinal progression of CEA is signicantly associated with the probability of survival of these patients. Hence, an assumption of

Protection, promotion and support of breast-feeding in Europe: progress from 2002 to 2007.

Science.gov (United States)

Cattaneo, Adriano; Burmaz, Tea; Arendt, Maryse; Nilsson, Ingrid; Mikiel-Kostyra, Krystyna; Kondrate, Irena; Communal, Marie José; Massart, Catherine; Chapin, Elise; Fallon, Maureen

2010-06-01

To assess progress in the protection, promotion and support of breast-feeding in Europe. Data for 2002 and 2007 were gathered with the same questionnaire. Of thirty countries, twenty-nine returned data for 2002, twenty-four for 2007. The number of countries with national policies complying with WHO recommendations increased. In 2007, six countries lacked a national policy, three a national plan, four a national breast-feeding coordinator and committee. Little improvement was reported in pre-service training; however, the number of countries with good coverage in the provision of WHO/UNICEF courses for in-service training increased substantially, as reflected in a parallel increase in the number of Baby Friendly Hospitals and the proportion of births taking place in them. Little improvement was reported as far as implementation of the International Code on Marketing of Breastmilk Substitutes is concerned. Except for Ireland and the UK, where some improvement occurred, no changes were reported on maternity protection. Due to lack of standard methods, it was difficult to compare rates of breast-feeding among countries. With this in mind, slight improvements in the rates of initiation, exclusivity and duration were reported by countries where data at two points in time were available. Breast-feeding rates continue to fall short of global recommendations. National policies are improving slowly but are hampered by the lack of action on maternity protection and the International Code. Pre-service training and standard monitoring of breast-feeding rates are the areas where more efforts are needed to accelerate progress.

Evaporation by mechanical vapor recompression. Technical progress report, September 1-December 31, 1979

Energy Technology Data Exchange (ETDEWEB)

Iverson, C.H.; Coury, G.E.

1979-01-01

Progress to date in the development of a study of the application of the technologies of mechanical vapor recompression and falling film evaporators as applied to the beet sugar industry is reported. Progress is reported in the following areas: technical literature search and plant visitations of existing applications of VR/FFE.

Does Skeletal Muscle Mass Influence Breast Cancer? Evaluating Mammary Tumorigenesis and Progression Genetically Hyper-Muscular Mice

Science.gov (United States)

2006-07-01

the skeletal muscle-specific muscle growth inhibitor myostatin and mice expressing a dominant negative form of the myostatin receptor, Activin...and rates of breast cancer initiation and progression. 15. SUBJECT TERMS Breast cancer, skeletal muscle, myostatin , MPA, DMBA, Activin receptor 16...including interleukins, Insulin-like Growth Factor (IGF) isoforms, IGF-binding proteins and myostatin . To determine the effect of skeletal muscle mass

Global Expression Profiling and Pathway Analysis of Mouse Mammary Tumor Reveals Strain and Stage Specific Dysregulated Pathways in Breast Cancer Progression.

Science.gov (United States)

Mei, Yan; Yang, Jun-Ping; Lang, Yan-Hong; Peng, Li-Xia; Yang, Ming-Ming; Liu, Qin; Meng, Dong-Fang; Zheng, Li-Sheng; Qiang, Yuan-Yuan; Xu, Liang; Li, Chang-Zhi; Wei, Wen-Wen; Niu, Ting; Peng, Xing-Si; Yang, Qin; Lin, Fen; Hu, Hao; Xu, Hong-Fa; Huang, Bi-Jun; Wang, Li-Jing; Qian, Chao-Nan

2018-05-01

It is believed that the alteration of tissue microenvironment would affect cancer initiation and progression. However, little is known in terms of the underlying molecular mechanisms that would affect the initiation and progression of breast cancer. In the present study, we use two murine mammary tumor models with different speeds of tumor initiation and progression for whole genome expression profiling to reveal the involved genes and signaling pathways. The pathways regulating PI3K-Akt signaling and Ras signaling were activated in Fvb mice and promoted tumor progression. Contrastingly, the pathways regulating apoptosis and cellular senescence were activated in Fvb.B6 mice and suppressed tumor progression. We identified distinct patterns of oncogenic pathways activation at different stages of breast cancer, and uncovered five oncogenic pathways that were activated in both human and mouse breast cancers. The genes and pathways discovered in our study would be useful information for other researchers and drug development.

Randomized controlled trial to evaluate the effects of progressive resistance training compared to progressive muscle relaxation in breast cancer patients undergoing adjuvant radiotherapy: the BEST study

International Nuclear Information System (INIS)

Potthoff, Karin; Steindorf, Karen; Schmidt, Martina E; Wiskemann, Joachim; Hof, Holger; Klassen, Oliver; Habermann, Nina; Beckhove, Philipp; Debus, Juergen; Ulrich, Cornelia M

2013-01-01

Cancer-related fatigue (CRF) is one of the most common and distressing side effects of cancer and its treatment. During and after radiotherapy breast cancer patients often suffer from CRF which frequently impairs quality of life (QoL). Despite the high prevalence of CRF in breast cancer patients and the severe impact on the physical and emotional well-being, effective treatment methods are scarce. Physical activity for breast cancer patients has been reported to decrease fatigue, to improve emotional well-being and to increase physical strength. The pathophysiological and molecular mechanisms of CRF and the molecular-biologic changes induced by exercise, however, are poorly understood. In the BEST trial we aim to assess the effects of resistance training on fatigue, QoL and physical fitness as well as on molecular, immunological and inflammatory changes in breast cancer patients during adjuvant radiotherapy. The BEST study is a prospective randomized, controlled intervention trial investigating the effects of a 12-week supervised progressive resistance training compared to a 12-week supervised muscle relaxation training in 160 patients with breast cancer undergoing adjuvant radiotherapy. To determine the effect of exercise itself beyond potential psychosocial group effects, patients in the control group perform a group-based progressive muscle relaxation training. Main inclusion criterion is histologically confirmed breast cancer stage I-III after lumpectomy or mastectomy with indication for adjuvant radiotherapy. Main exclusion criteria are acute infectious diseases, severe neurological, musculosceletal or cardiorespiratory disorders. The primary endpoint is cancer-related fatigue; secondary endpoints include immunological and inflammatory parameters analyzed in peripheral blood, saliva and urine. In addition, QoL, depression, physical performance and cognitive capacity will be assessed. The BEST study is the first randomized controlled trial comparing progressive

Multimodal Analgesia in Breast Surgical Procedures: Technical and Pharmacological Considerations for Liposomal Bupivacaine Use

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Anoushka M. Afonso, MD

2017-09-01

Full Text Available Enhanced recovery after surgery is a multidisciplinary perioperative clinical pathway that uses evidence-based interventions to improve the patient experience as well as increase satisfaction, reduce costs, mitigate the surgical stress response, accelerate functional recovery, and decrease perioperative complications. One of the most important elements of enhanced recovery pathways is multimodal pain management. Herein, aspects relating to multimodal analgesia following breast surgical procedures are discussed with the understanding that treatment decisions should be individualized and guided by sound clinical judgment. A review of liposomal bupivacaine, a prolonged-release formulation of bupivacaine, in the management of postoperative pain following breast surgical procedures is presented, and technical guidance regarding optimal administration of liposomal bupivacaine is provided.

Experimental Facilities Division/User Program Division technical progress report 1999-2000

International Nuclear Information System (INIS)

2001-01-01

In October 1999, the two divisions of the Advanced Photon Source (APS), the Accelerator Systems Division (ASD) and the Experimental Facilities Division (XFD), were reorganized into four divisions (see high-level APS organizational chart, Fig. 1.1). In addition to ASD and XFD, two new divisions were created, the APS Operations Division (AOD), to oversee APS operations, and the User Program Division (UPD), to serve the APS user community by developing and maintaining the highest quality user technical and administration support. Previous XFD Progress Reports (ANL/APS/TB-30 and ANL/APS/TB-34) covered a much broader base, including APS user administrative support and what was previously XFD operations (front ends, interlocks, etc.) This Progress Report summarizes the main scientific and technical activities of XFD, and the technical support, research and development (R and D) activities of UPD from October 1998 through November 2000. The report is divided into four major sections, (1) Introduction, (2) SRI-CAT Beamlines, Technical Developments, and Scientific Applications, (3) User Technical Support, and (4) Major Plans for the Future. Sections 2 and 3 describe the technical activities and research accomplishments of the XFD and UPD personnel in supporting the synchrotron radiation instrumentation (SRI) collaborative access team (CAT) and the general APS user community. Also included in this report is a comprehensive list of publications (Appendix 1) and presentations (Appendix 2) by XFD and UPD staff during the time period covered by this report. The organization of section 2, SRI CAT Beamlines, Technical Developments, and Scientific Applications has been made along scientific techniques/disciplines and not ''geographical'' boundaries of the sectors in which the work was performed. Therefore items under the subsection X-ray Imaging and Microfocusing could have been (and were) performed on several different beamlines by staff in different divisions. The management of

PBX1 Genomic Pioneer Function Drives ERα Signaling Underlying Progression in Breast Cancer

Science.gov (United States)

Magnani, Luca; Ballantyne, Elizabeth B.; Zhang, Xiaoyang; Lupien, Mathieu

2011-01-01

Altered transcriptional programs are a hallmark of diseases, yet how these are established is still ill-defined. PBX1 is a TALE homeodomain protein involved in the development of different types of cancers. The estrogen receptor alpha (ERα) is central to the development of two-thirds of all breast cancers. Here we demonstrate that PBX1 acts as a pioneer factor and is essential for the ERα-mediated transcriptional response driving aggressive tumors in breast cancer. Indeed, PBX1 expression correlates with ERα in primary breast tumors, and breast cancer cells depleted of PBX1 no longer proliferate following estrogen stimulation. Profiling PBX1 recruitment and chromatin accessibility across the genome of breast cancer cells through ChIP-seq and FAIRE-seq reveals that PBX1 is loaded and promotes chromatin openness at specific genomic locations through its capacity to read specific epigenetic signatures. Accordingly, PBX1 guides ERα recruitment to a specific subset of sites. Expression profiling studies demonstrate that PBX1 controls over 70% of the estrogen response. More importantly, the PBX1-dependent transcriptional program is associated with poor-outcome in breast cancer patients. Correspondingly, PBX1 expression alone can discriminate a priori the outcome in ERα-positive breast cancer patients. These features are markedly different from the previously characterized ERα-associated pioneer factor FoxA1. Indeed, PBX1 is the only pioneer factor identified to date that discriminates outcome such as metastasis in ERα-positive breast cancer patients. Together our results reveal that PBX1 is a novel pioneer factor defining aggressive ERα-positive breast tumors, as it guides ERα genomic activity to unique genomic regions promoting a transcriptional program favorable to breast cancer progression. PMID:22125492

Expression of neurotensin and NT1 receptor in human breast cancer: a potential role in tumor progression.

Science.gov (United States)

Souazé, Frédérique; Dupouy, Sandra; Viardot-Foucault, Véronique; Bruyneel, Erik; Attoub, Samir; Gespach, Christian; Gompel, Anne; Forgez, Patricia

2006-06-15

Emerging evidence supports neurotensin as a trophic and antiapoptotic factor, mediating its control via the high-affinity neurotensin receptor (NT1 receptor) in several human solid tumors. In a series of 51 patients with invasive ductal breast cancers, 34% of all tumors were positive for neurotensin and 91% positive for NT1 receptor. We found a coexpression of neurotensin and NT1 receptor in a large proportion (30%) of ductal breast tumors, suggesting a contribution of the neurotensinergic signaling cascade within breast cancer progression. Functionally expressed NT1 receptor, in the highly malignant MDA-MB-231 human breast cancer cell line, coordinated a series of transforming functions, including cellular migration, invasion, induction of the matrix metalloproteinase (MMP)-9 transcripts, and MMP-9 gelatinase activity. Disruption of NT1 receptor signaling by silencing RNA or use of a specific NT1 receptor antagonist, SR48692, caused the reversion of these transforming functions and tumor growth of MDA-MB-231 cells xenografted in nude mice. Our findings support the contribution of neurotensin in human breast cancer progression and point out the utility to develop therapeutic molecules targeting neurotensin or NT1 receptor signaling cascade. These strategies would increase the range of therapeutic approaches and be beneficial for specific patients.

The E-cadherin/catenin complex: an important gatekeeper in breast cancer tumorigenesis and malignant progression

International Nuclear Information System (INIS)

Berx, Geert; Roy, Frans Van

2001-01-01

E-cadherin is a cell–cell adhesion protein fulfilling a prominent role in epithelial differentiation. Data from model systems suggest that E-cadherin is a potent invasion/tumor suppressor of breast cancer. Consistent with this role in breast cancer progression, partial or complete loss of E-cadherin expression has been found to correlate with poor prognosis in breast cancer patients. The E-cadherin gene (CDH1) is located on human chromosome 16q22.1, a region frequently affected with loss of heterozygosity in sporadic breast cancer. Invasive lobular breast carcinomas, which are typically completely E-cadherin-negative, often show inactivating mutations in combination with loss of heterozygosity of the wild-type CDH1 allele. Mutations were found at early noninvasive stages, thus associating E-cadherin mutations with loss of cell growth control and defining CDH1 as the tumor suppressor for the lobular breast cancer subtype. Ductal breast cancers in general show heterogeneous loss of E-cadherin expression, associated with epigenetic transcriptional downregulation. It is proposed that the microenvironment at the invasive front is transiently downregulating E-cadherin transcription. This can be associated with induction of nonepithelial cadherins

The associations between the environmental exposure to polychlorinated biphenyls (PCBs) and breast cancer risk and progression

Institute of Scientific and Technical Information of China (English)

无

2010-01-01

Polychlorinated biphenyls(PCBs) are chlorinated biphenyl compounds with wide applications in the industry.In spite of a ban on their production in the late 1970s,PCBs,as a group of POPs,are still persistent and widely spread in the environment,posing potential threats to human health.The role of PCBs as etiologic agents for breast cancer has been intensively explored in a variety of in vivo,animal and epidemiologic studies.Initial investigations indicated higher levels of PCBs in mammary tissues or sera corresponded to the occurrence of breast cancer,but later studies showed no positive association between PCB exposure and breast cancer development.More recent data suggested that the CYP1A1 m2 polymorphisms might add increased risk to the etiology of breast cancer in women with environmental exposure to PCBs.PCBs are implicated in advancing breast cancer progression,and our unpublished data reveals that PCBs activate the ROCK signaling to enhance breast cancer metastasis.Therefore,the correlation between PCB exposure and breast cancer risk warrants further careful investigations.

A male patient with acromegaly and breast cancer: treating acromegaly to control tumor progression

International Nuclear Information System (INIS)

Leporati, Paola; Fonte, Rodolfo; Martinis, Luca de; Zambelli, Alberto; Magri, Flavia; Pavesi, Lorenzo; Rotondi, Mario; Chiovato, Luca

2015-01-01

Acromegaly is a rare disease associated with an increased risk of developing cancer. We report the case of a 72-year-old man who was diagnosed with acromegaly (IGF-1 770 ng/ml) and breast cancer. Four years before he suffered from a colon-rectal cancer. Pituitary surgery and octreotide-LAR treatment failed to control acromegaly. Normalization of IGF-1 (97 ng/ml) was obtained with pegvisomant therapy. Four years after breast cancer surgery, 2 pulmonary metastases were detected at chest CT. The patient was started on anastrozole, but, contrary to medical advice, he stopped pegvisomant treatment (IGF-I 453 ng/ml). Four months later, chest CT revealed an increase in size of the metastatic lesion of the left lung. The patient was shifted from anastrozole to tamoxifen and was restarted on pegvisomant, with normalization of serum IGF-1 levels (90 ng/ml). Four months later, a reduction in size of the metastatic lesion of the left lung was detected by CT. Subsequent CT scans throughout a 24-month follow-up showed a further reduction in size and then a stabilization of the metastasis. This is the first report of a male patient with acromegaly and breast cancer. The clinical course of breast cancer was closely related to the metabolic control of acromegaly. The rapid progression of metastatic lesion was temporally related to stopping pegvisomant treatment and paralleled a rise in serum IGF-1 levels. Normalization of IGF-1 after re-starting pegvisomant impressively reduced the progression of metastatic breast lesions. Control of acromegaly is mandatory in acromegalic patients with cancer. The online version of this article (doi:10.1186/s12885-015-1400-0) contains supplementary material, which is available to authorized users

Breast Cancer Patients Have Greatly Benefited from the Progress in Molecular Oncology.

Directory of Open Access Journals (Sweden)

Bernd L Groner

2016-09-01

Full Text Available Cancer research has become a global enterprise, and the number of researchers, as well as the cost for their activities, has skyrocketed. The budget for the National Cancer Institute of the United States National Institutes of Health alone was US$5.2 billion in 2015. Since most of the research is funded by public money, it is perfectly legitimate to ask if these large expenses are worth it. In this brief commentary, we recapitulate some of the breakthroughs that mark the history of breast cancer research over the past decades and emphasize the resulting benefits for afflicted women. In 1971, only 40% of women diagnosed with breast cancer would live another 10 years. Today, nearly 80% of women reach that significant milestone in most developed countries. This dramatic change has afforded breast cancer patients many productive years and a better quality of life. Progress resulted largely from advances in the understanding of the molecular details of the disease and their translation into innovative, rationally designed therapies. These developments are founded on the revolution in molecular and cellular biology, an entirely new array of methods and technologies, the enthusiasm, optimism, and diligence of scientists and clinicians, and the considerable funding efforts from public and private sources. We were lucky to be able to spend our productive years in a period of scientific upheaval in which methods and concepts were revolutionized and that allowed us to contribute, within the global scientific community, to the progress in basic science and clinical practice.

Breast Cancer Patients Have Greatly Benefited from the Progress in Molecular Oncology.

Science.gov (United States)

Groner, Bernd L; Hynes, Nancy E

2016-09-01

Cancer research has become a global enterprise, and the number of researchers, as well as the cost for their activities, has skyrocketed. The budget for the National Cancer Institute of the United States National Institutes of Health alone was US$5.2 billion in 2015. Since most of the research is funded by public money, it is perfectly legitimate to ask if these large expenses are worth it. In this brief commentary, we recapitulate some of the breakthroughs that mark the history of breast cancer research over the past decades and emphasize the resulting benefits for afflicted women. In 1971, only 40% of women diagnosed with breast cancer would live another 10 years. Today, nearly 80% of women reach that significant milestone in most developed countries. This dramatic change has afforded breast cancer patients many productive years and a better quality of life. Progress resulted largely from advances in the understanding of the molecular details of the disease and their translation into innovative, rationally designed therapies. These developments are founded on the revolution in molecular and cellular biology, an entirely new array of methods and technologies, the enthusiasm, optimism, and diligence of scientists and clinicians, and the considerable funding efforts from public and private sources. We were lucky to be able to spend our productive years in a period of scientific upheaval in which methods and concepts were revolutionized and that allowed us to contribute, within the global scientific community, to the progress in basic science and clinical practice.

Technical success, technique efficacy and complications of minimally-invasive imaging-guided percutaneous ablation procedures of breast cancer: A systematic review and meta-analysis.

Science.gov (United States)

Mauri, Giovanni; Sconfienza, Luca Maria; Pescatori, Lorenzo Carlo; Fedeli, Maria Paola; Alì, Marco; Di Leo, Giovanni; Sardanelli, Francesco

2017-08-01

To systematically review studies concerning imaging-guided minimally-invasive breast cancer treatments. An online database search was performed for English-language articles evaluating percutaneous breast cancer ablation. Pooled data and 95% confidence intervals (CIs) were calculated. Technical success, technique efficacy, minor and major complications were analysed, including ablation technique subgroup analysis and effect of tumour size on outcome. Forty-five studies were analysed, including 1,156 patients and 1,168 lesions. Radiofrequency (n=577; 50%), microwaves (n=78; 7%), laser (n=227; 19%), cryoablation (n=156; 13%) and high-intensity focused ultrasound (HIFU, n=129; 11%) were used. Pooled technical success was 96% (95%CI 94-97%) [laser=98% (95-99%); HIFU=96% (90-98%); radiofrequency=96% (93-97%); cryoablation=95% (90-98%); microwave=93% (81-98%)]. Pooled technique efficacy was 75% (67-81%) [radiofrequency=82% (74-88); cryoablation=75% (51-90); laser=59% (35-79); HIFU=49% (26-74)]. Major complications pooled rate was 6% (4-8). Minor complications pooled rate was 8% (5-13%). Differences between techniques were not significant for technical success (p=0.449), major complications (p=0.181) or minor complications (p=0.762), but significant for technique efficacy (p=0.009). Tumour size did not impact on variables (p>0.142). Imaging-guided percutaneous ablation techniques of breast cancer have a high rate of technical success, while technique efficacy remains suboptimal. Complication rates are relatively low. • Imaging-guided ablation techniques for breast cancer are 96% technically successful. • Overall technique efficacy rate is 75% but largely inhomogeneous among studies. • Overall major and minor complication rates are low (6-8%).

Re-Appraisal of Estrogen Receptor Negative/Progesterone Receptor Positive (ER-/PR+) Breast Cancer Phenotype: True Subtype or Technical Artefact?

Science.gov (United States)

Foley, Niamh M; Coll, J M; Lowery, A J; Hynes, S O; Kerin, M J; Sheehan, M; Brodie, C; Sweeney, K J

2017-09-11

Expression of the ER and PR receptors is routinely quantified in breast cancer as a predictive marker of response to hormonal therapy. Accurate determination of ER and PR status is critical to the optimal selection of patients for targeted therapy. The existence of an ER-/PR+ subtype is controversial, with debate centred on whether this represents a true phenotype or a technical artefact on immunohistochemistry (IHC). The aim of this study was to investigate the true incidence and clinico-pathological features of ER-/PR+ breast cancers in a tertiary referral symptomatic breast unit. Clinico-pathological data were collected on invasive breast cancers diagnosed between 1995 and 2005. IHC for ER and PR receptors was repeated on all cases which were ER-/PR+, with the same paraffin block used for the initial diagnostic testing. Concordance between the diagnostic and repeat IHC was determined using validated testing. Complete data, including ER and PR status were available for 697 patients diagnosed during the study period. On diagnostic IHC, the immunophenotype of the breast tumours was: ER+/PR+ in 396 (57%), ER-/PR- in 157 (23%), ER+/PR- in 88 (12%) and ER-/PR+ in 56 (8.6%) patients. On repeat IHC of 48/56 ER-/PR+ tumours 45.8% were ER+/PR+, 6% were ER+/PR- and 43.7% were ER-/PR- None of the cases were confirmed to be ER-/PR+. The ER-/PR+ phenotypic breast cancer is likely to be the result of technical artefact. Prompt reassessment of patients originally assigned to this subtype who re-present with symptoms should be considered to ensure appropriate clinical management.

Technical feasibility proof for high-resolution low-dose photon-counting CT of the breast

Energy Technology Data Exchange (ETDEWEB)

Kalender, Willi A.; Kolditz, Daniel; Lueck, Ferdinand [University of Erlangen-Nuernberg, Institute of Medical Physics (IMP), Erlangen (Germany); CT Imaging GmbH, Erlangen (Germany); Steiding, Christian [University of Erlangen-Nuernberg, Institute of Medical Physics (IMP), Erlangen (Germany); CT Imaging GmbH, Erlangen (Germany); University Hospital of Erlangen, Institute of Radiology, Erlangen (Germany); Ruth, Veikko; Roessler, Ann-Christin [University of Erlangen-Nuernberg, Institute of Medical Physics (IMP), Erlangen (Germany); Wenkel, Evelyn [University Hospital of Erlangen, Institute of Radiology, Erlangen (Germany)

2017-03-15

X-ray computed tomography (CT) has been proposed and evaluated multiple times as a potentially alternative method for breast imaging. All efforts shown so far have been criticized and partly disapproved because of their limited spatial resolution and higher patient dose when compared to mammography. Our concept for a dedicated breast CT (BCT) scanner therefore aimed at novel apparatus and detector design to provide high spatial resolution of about 100 μm and average glandular dose (AGD) levels of 5 mGy or below. Photon-counting technology was considered as a solution to reach these goals. The complete concept was previously evaluated and confirmed by simulations and basic experiments on laboratory setups. We here present measurements of dose, technical image quality parameters and surgical specimen results on such a scanner. For comparison purposes, the specimens were also imaged with digital mammography (DM) and breast tomosynthesis (BT) apparatus. Results show that photon-counting BCT (pcBCT) at 5 mGy AGD offers sufficiently high 3D spatial resolution for reliable detectability of calcifications and soft tissue delineation. (orig.)

MFAP5 promotes tumor progression and bone metastasis by regulating ERK/MMP signaling pathways in breast cancer.

Science.gov (United States)

Wu, Zhiqiang; Wang, Ting; Fang, Meng; Huang, Wending; Sun, Zhengwang; Xiao, Jianru; Yan, Wangjun

2018-04-06

Breast cancer accounts for about 30% of all cancers in women, while approximately 70% breast cancer patients developed bone metastases throughout the course of their disease, highlighting the importance of exploring new therapeutic targets. Microfibrillar-associated protein 5 (MFAP5) is a component of extracellular elastic microfibril which has been confirmed to function in tissue development and cancer progression. But the role of MFAP5 in breast cancer remains unclear. The present study demonstrated that MFAP5 was up-regulated in breast cancers compared with that in normal breast tissues, and further increased in breast cancer bone metastasis. Functionally, MFAP5 overexpression accelerated breast cancer cell proliferation and migration, while an opposite effect was observed when MFAP5 was knocked down. In addition, up-regulation of MFAP5 increased the expression of MMP2 and MMP9 and activated the ERK signaling pathway. Conversely, inhibition of MFAP5 suppressed the expression of MMP2, MMP9, p-FAK, p-Erk1/2 and p-cJun. These findings may provide a better understanding about the mechanism of breast cancer and suggest that MFAP5 may be a potential prognostic biomarker and therapeutic target for breast cancer, especially for bone metastasis of breast cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

Analysis of the progression of fibroepithelial tumours of the breast by PCR-based clonality assay

NARCIS (Netherlands)

Kuijper, Arno; Buerger, H.; Simon, R.; Schaefer, K-L.; Croonen, A.; Boecker, W.; Wall, E. van der; Diest, P.J. van

2002-01-01

Fibroadenoma and phyllodes tumour of the breast are both fibroepithelial tumours. Although progression to epithelial malignancy has been described, the behaviour of most fibroadenomas is benign. Phyllodes tumours, on the other hand, can display locally destructive growth and can even metastasize. A

Tangential breast irradiation - rationale and methods for improving dosimetry

International Nuclear Information System (INIS)

Neal, A.J.; Mayles, W.P.M.; Yarnold, J.R.

1994-01-01

In recent years there have been great advances and innovations in all technical aspects of radiotherapy, including three dimensional (3D) computer planning, patient immobilization, radiation delivery and treatment verification. Despite this progress, the technique of tangential breast irradiation has changed little over this period and has not exploited these advances. There is increasing evidence that dose inhomogeneity within the breast is greater than at other anatomical sites, especially in women with large breasts. This paper is a review of the factors contributing to poor dosimetry in the breast, the clinical consequences of an inhomogeneous dose distribution, and how breast dosimetry could be improved by considering each of the stages from planning to accurate treatment delivery. It also highlights the particular problem of women with large breasts who may be more likely to have a poorer outcome after a fractionated course of radiotherapy than women with small/medium-sized breasts, and supports the clinical impression that such women are also more likely to have greater inhomogenicity when 3D treatment plans are examined. Preliminary data from our current computed tomography (CT) planning study are presented to support these observations. (author)

Transcriptomic changes in human breast cancer progression as determined by serial analysis of gene expression

International Nuclear Information System (INIS)

Abba, Martin C; Aldaz, C Marcelo; Drake, Jeffrey A; Hawkins, Kathleen A; Hu, Yuhui; Sun, Hongxia; Notcovich, Cintia; Gaddis, Sally; Sahin, Aysegul; Baggerly, Keith

2004-01-01

Genomic and transcriptomic alterations affecting key cellular processes such us cell proliferation, differentiation and genomic stability are considered crucial for the development and progression of cancer. Most invasive breast carcinomas are known to derive from precursor in situ lesions. It is proposed that major global expression abnormalities occur in the transition from normal to premalignant stages and further progression to invasive stages. Serial analysis of gene expression (SAGE) was employed to generate a comprehensive global gene expression profile of the major changes occurring during breast cancer malignant evolution. In the present study we combined various normal and tumor SAGE libraries available in the public domain with sets of breast cancer SAGE libraries recently generated and sequenced in our laboratory. A recently developed modified t test was used to detect the genes differentially expressed. We accumulated a total of approximately 1.7 million breast tissue-specific SAGE tags and monitored the behavior of more than 25,157 genes during early breast carcinogenesis. We detected 52 transcripts commonly deregulated across the board when comparing normal tissue with ductal carcinoma in situ, and 149 transcripts when comparing ductal carcinoma in situ with invasive ductal carcinoma (P < 0.01). A major novelty of our study was the use of a statistical method that correctly accounts for the intra-SAGE and inter-SAGE library sources of variation. The most useful result of applying this modified t statistics beta binomial test is the identification of genes and gene families commonly deregulated across samples within each specific stage in the transition from normal to preinvasive and invasive stages of breast cancer development. Most of the gene expression abnormalities detected at the in situ stage were related to specific genes in charge of regulating the proper homeostasis between cell death and cell proliferation. The comparison of in situ lesions

The effects of environmental regulation and technical progress on CO2 Kuznets curve: An evidence from China

International Nuclear Information System (INIS)

Yin, Jianhua; Zheng, Mingzheng; Chen, Jian

2015-01-01

Based on environmental Kuznets curve theory, a panel data model which takes environmental regulation and technical progress as its moderating factors was developed to analyse the institutional and technical factors that affect the path of low-carbon economic development. The results indicated that there was a CO 2 emission Kuznets curve seen in China. Environmental regulation had a significant moderating effect on the curve, and the inflection of CO 2 emissions could come substantially earlier under stricter environmental regulation. Meanwhile, the impact of technical progress on the low-carbon economic development path had a longer hysteresis effect but restrained CO 2 emission during its increasing stage and accelerated its downward trend during the decreasing stage which was conducive to emission reduction. Strict environmental regulation could force the high-carbon emitting industries to transfer from the eastern regions to the central or the western regions of China, which would make the CO 2 Kuznets curve higher in its increasing stage and lower in its decreasing stage than that under looser regulation. Furthermore, energy efficiency, energy structure, and industrial structure exerted a significant direct impact on CO 2 emissions; we should consider the above factors as essential in the quest for low-carbon economic development. - Highlights: • Estimate moderating effect of environmental regulation and technical progress on EKC. • There was a CO 2 emission Kuznets curve in effect in China. • Environmental regulation presents significant moderating effect on EKC. • Technical progress moderates the relationship between income and CO 2 emissions

Morphine does not facilitate breast cancer progression in two preclinical mouse models for human invasive lobular and HER2⁺ breast cancer.

Science.gov (United States)

Doornebal, Chris W; Vrijland, Kim; Hau, Cheei-Sing; Coffelt, Seth B; Ciampricotti, Metamia; Jonkers, Jos; de Visser, Karin E; Hollmann, Markus W

2015-08-01

Morphine and other opioid analgesics are potent pain-relieving agents routinely used for pain management in patients with cancer. However, these drugs have recently been associated with a worse relapse-free survival in patients with surgical cancer, thus suggesting that morphine adversely affects cancer progression and relapse. In this study, we evaluated the impact of morphine on breast cancer progression, metastatic dissemination, and outgrowth of minimal residual disease. Using preclinical mouse models for metastatic invasive lobular and HER2 breast cancer, we show that analgesic doses of morphine do not affect mammary tumor growth, angiogenesis, and the composition of tumor-infiltrating immune cells. Our studies further demonstrate that morphine, administered in the presence or absence of surgery-induced tissue damage, neither facilitates de novo metastatic dissemination nor promotes outgrowth of minimal residual disease after surgery. Together, these findings indicate that opioid analgesics can be used safely for perioperative pain management in patients with cancer and emphasize that current standards of "good clinical practice" should be maintained.

ERIP invention 637. Technical progress report 2nd quarter, April 1997--June 1997

Energy Technology Data Exchange (ETDEWEB)

Thacker, G.W.

1997-07-22

This technical report describes progress in the development of the Pegasus plow, a stalk and root embedding apparatus. Prototype testing is reported, and includes the addition of precision tillage. Disease data, organic matter, and nitrogen levels results are very briefly described. Progress in marketing is also reported. Current marketing issues include test use by cotton and wheat growers, establishment of dealer relationships, incorporation of design modifications, expansion of marketing activities, and expansion of loan and lease program.

Withaferin A and sulforaphane regulate breast cancer cell cycle progression through epigenetic mechanisms.

Science.gov (United States)

Royston, Kendra J; Paul, Bidisha; Nozell, Susan; Rajbhandari, Rajani; Tollefsbol, Trygve O

2018-07-01

Little is known about the effects of combinatorial dietary compounds on the regulation of epigenetic mechanisms involved in breast cancer prevention. The human diet consists of a multitude of components, and there is a need to elucidate how certain compounds interact in collaboration. Withaferin A (WA), found in the Indian winter cherry and documented as a DNA methyltransferase (DNMT) inhibitor, and sulforaphane (SFN), a well-known histone deacetylase (HDAC) inhibitor found in cruciferous vegetables, are two epigenetic modifying compounds that have only recently been studied in conjunction. The use of DNMT and HDAC inhibitors to reverse the malignant expression of certain genes in breast cancer has shown considerable promise. Previously, we found that SFN + WA synergistically promote breast cancer cell death. Herein, we determined that these compounds inhibit cell cycle progression from S to G2 phase in MDA-MB-231 and MCF-7 breast cancer. Furthermore, we demonstrate that this unique combination of epigenetic modifying compounds down-regulates the levels of Cyclin D1 and CDK4, and pRB; conversely, the levels of E2F mRNA and tumor suppressor p21 are increased independently of p53. We find these events coincide with an increase in unrestricted histone methylation. We propose SFN + WA-induced breast cancer cell death is attributed, in part, to epigenetic modifications that result in the modulated expression of key genes responsible for the regulation of cancer cell senescence. Copyright © 2018 Elsevier Inc. All rights reserved.

n-Butyl benzyl phthalate promotes breast cancer progression by inducing expression of lymphoid enhancer factor 1.

Directory of Open Access Journals (Sweden)

Tsung-Hua Hsieh

Full Text Available Environmental hormones play important roles in regulating the expression of genes involved in cell proliferation, drug resistance, and breast cancer risk; however, their precise role in human breast cancer cells during cancer progression remains unclear. To elucidate the effect of the most widely used industrial phthalate, n-butyl benzyl phthalate (BBP, on cancer progression, we evaluated the results of BBP treatment using a whole human genome cDNA microarray and MetaCore software and selected candidate genes whose expression was changed by more than ten-fold by BBP compared with controls to analyze the signaling pathways in human breast cancer initiating cells (R2d. A total of 473 genes were upregulated, and 468 were downregulated. Most of these genes are involved in proliferation, epithelial-mesenchymal transition, and angiogenesis signaling. BBP induced the viability, invasion and migration, and tube formation in vitro, and Matrigel plug angiogenesis in vivo of R2d and MCF-7. Furthermore, the viability and invasion and migration of these cell lines following BBP treatment was reduced by transfection with a small interfering RNA targeting the mRNA for lymphoid enhancer-binding factor 1; notably, the altered expression of this gene consistently differentiated tumors expressing genes involved in proliferation, epithelial-mesenchymal transition, and angiogenesis. These findings contribute to our understanding of the molecular impact of the environmental hormone BBP and suggest possible strategies for preventing and treating human breast cancer.

The role of microRNA-200 in progression of human colorectal and breast cancer.

Directory of Open Access Journals (Sweden)

Linda Bojmar

Full Text Available The role of the epithelial-mesenchymal transition (EMT in cancer has been studied extensively in vitro, but involvement of the EMT in tumorigenesis in vivo is largely unknown. We investigated the potential of microRNAs as clinical markers and analyzed participation of the EMT-associated microRNA-200-ZEB-E-cadherin pathway in cancer progression. Expression of the microRNA-200 family was quantified by real-time RT-PCR analysis of fresh-frozen and microdissected formalin-fixed paraffin-embedded primary colorectal tumors, normal colon mucosa, and matched liver metastases. MicroRNA expression was validated by in situ hybridization and after in vitro culture of the malignant cells. To assess EMT as a predictive marker, factors considered relevant in colorectal cancer were investigated in 98 primary breast tumors from a treatment-randomized study. Associations between the studied EMT-markers were found in primary breast tumors and in colorectal liver metastases. MicroRNA-200 expression in epithelial cells was lower in malignant mucosa than in normal mucosa, and was also decreased in metastatic compared to non-metastatic colorectal cancer. Low microRNA-200 expression in colorectal liver metastases was associated with bad prognosis. In breast cancer, low levels of microRNA-200 were related to reduced survival and high expression of microRNA-200 was predictive of benefit from radiotheraphy. MicroRNA-200 was associated with ER positive status, and inversely correlated to HER2 and overactivation of the PI3K/AKT pathway, that was associated with high ZEB1 mRNA expression. Our findings suggest that the stability of microRNAs makes them suitable as clinical markers and that the EMT-related microRNA-200-ZEB-E-cadherin signaling pathway is connected to established clinical characteristics and can give useful prognostic and treatment-predictive information in progressive breast and colorectal cancers.

Clinical Significance of HER-2 Splice Variants in Breast Cancer Progression and Drug Resistance

Directory of Open Access Journals (Sweden)

Claire Jackson

2013-01-01

Full Text Available Overexpression of human epidermal growth factor receptor (HER-2 occurs in 20–30% of breast cancers and confers survival and proliferative advantages on the tumour cells making HER-2 an ideal therapeutic target for drugs like Herceptin. Continued delineation of tumour biology has identified splice variants of HER-2, with contrasting roles in tumour cell biology. For example, the splice variant 16HER-2 (results from exon 16 skipping increases transformation of cancer cells and is associated with treatment resistance; conversely, Herstatin (results from intron 8 retention and p100 (results from intron 15 retention inhibit tumour cell proliferation. This review focuses on the potential clinical implications of the expression and coexistence of HER-2 splice variants in cancer cells in relation to breast cancer progression and drug resistance. “Individualised” strategies currently guide breast cancer management; in accordance, HER-2 splice variants may prove valuable as future prognostic and predictive factors, as well as potential therapeutic targets.

Cassini RTG Program. Monthly technical progress report, 27 November--31 December 1995

International Nuclear Information System (INIS)

1996-01-01

This monthly technical progress report provided information on the following tasks: spacecraft integration and liaison; engineering support; safety analysis; qualified unicouple fabrication; ETG fabrication, assembly, and test; ground support equipment (GSE); RTG shipping and launch support; designs, reviews, and mission applications; project management, quality assurance, and reliability, and contractor acquired government owned (CAGO) property acquisition

Impact of Environmental Regulation and Technical Progress on Industrial Carbon Productivity: An Approach Based on Proxy Measure

Directory of Open Access Journals (Sweden)

Huan Zhang

2016-08-01

Full Text Available This research aims to study the main influencing factors of China’s industrial carbon productivity by incorporating environmental regulation and technical progress into an econometric model. The paper focuses on data from 35 of China’s industrial sectors and covers the period from 2006 to 2014, in order to examine the impact of environmental regulation and technical progress on carbon productivity. Methods applied include panel fixed effect model, panel random effect model and two stage least squares with instrumental variables (IV-2SLS. The effect of environmental regulation and technical progress has industrial heterogeneity. The paper subdivides industrial sectors into capital and technology intensive, resource intensive and labor intensive sectors according to factor intensiveness. The estimation results of the subgroups have uncovered that for capital and technology intensive and resource intensive sectors, environmental regulation has a more significant impact than technical progress; while for labor intensive sectors, innovation more significantly influences carbon productivity. In addition, foreign direct investment (FDI and industrialization level facilitate improving carbon productivity for the full sample. By contrast, industrial structure inhibits the overall industrial carbon productivity. The industry-specific results indicate that for capital and technology intensive sectors, optimizing of the industrial structure can improve carbon productivity; for resource intensive sectors, FDI and energy consumption structure should be emphasized more; for labor intensive sectors, industrialization levels help enhance carbon productivity. Finally the industrial sector-specific policy suggestions are proposed.

Microenvironmental Heterogeneity Parallels Breast Cancer Progression: A Histology-Genomic Integration Analysis.

Directory of Open Access Journals (Sweden)

Rachael Natrajan

2016-02-01

Full Text Available The intra-tumor diversity of cancer cells is under intense investigation; however, little is known about the heterogeneity of the tumor microenvironment that is key to cancer progression and evolution. We aimed to assess the degree of microenvironmental heterogeneity in breast cancer and correlate this with genomic and clinical parameters.We developed a quantitative measure of microenvironmental heterogeneity along three spatial dimensions (3-D in solid tumors, termed the tumor ecosystem diversity index (EDI, using fully automated histology image analysis coupled with statistical measures commonly used in ecology. This measure was compared with disease-specific survival, key mutations, genome-wide copy number, and expression profiling data in a retrospective study of 510 breast cancer patients as a test set and 516 breast cancer patients as an independent validation set. In high-grade (grade 3 breast cancers, we uncovered a striking link between high microenvironmental heterogeneity measured by EDI and a poor prognosis that cannot be explained by tumor size, genomics, or any other data types. However, this association was not observed in low-grade (grade 1 and 2 breast cancers. The prognostic value of EDI was superior to known prognostic factors and was enhanced with the addition of TP53 mutation status (multivariate analysis test set, p = 9 × 10-4, hazard ratio = 1.47, 95% CI 1.17-1.84; validation set, p = 0.0011, hazard ratio = 1.78, 95% CI 1.26-2.52. Integration with genome-wide profiling data identified losses of specific genes on 4p14 and 5q13 that were enriched in grade 3 tumors with high microenvironmental diversity that also substratified patients into poor prognostic groups. Limitations of this study include the number of cell types included in the model, that EDI has prognostic value only in grade 3 tumors, and that our spatial heterogeneity measure was dependent on spatial scale and tumor size.To our knowledge, this is the first

An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models

LENUS (Irish Health Repository)

Donatello, Simona

2011-04-26

Abstract Background Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression. Methods Primary cultures were established from human breast tumour and adjacent non-tumour tissue. Putative progenitor cell populations were isolated based on co-expression or concomitant absence of the epithelial and myoepithelial markers EPCAM and CALLA respectively. Results Significant reductions in cellular senescence were observed in tumour versus non-tumour cultures, accompanied by a stepwise increase in proliferation:senescence ratios. A novel correlation between tumour aggressiveness and an imbalance of putative progenitor subpopulations was also observed. Specifically, an increased double-negative (DN) to double-positive (DP) ratio distinguished aggressive tumours of high grade, estrogen receptor-negativity or HER2-positivity. The DN:DP ratio was also higher in malignant MDA-MB-231 cells relative to non-tumourogenic MCF-10A cells. Ultrastructural analysis of the DN subpopulation in an invasive tumour culture revealed enrichment in lipofuscin bodies, markers of ageing or senescent cells. Conclusions Our results suggest that an imbalance in tumour progenitor subpopulations imbalances the functional relationship between proliferation and senescence, creating a microenvironment favouring tumour progression.

BRD7 inhibits the Warburg effect and tumor progression through inactivation of HIF1α/LDHA axis in breast cancer.

Science.gov (United States)

Niu, Weihong; Luo, Yanwei; Wang, Xinye; Zhou, Yao; Li, Hui; Wang, Heran; Fu, Yaojie; Liu, Shanshan; Yin, Shanghelin; Li, Jianglei; Zhao, Ran; Liu, Yukun; Fan, Songqing; Li, Zheng; Xiong, Wei; Li, Xiaoling; Li, Guiyuan; Ren, Caiping; Tan, Ming; Zhou, Ming

2018-05-03

The bromodomain-containing protein 7 (BRD7) was first identified as a tumor suppressor in nasopharyngeal carcinoma and has critical roles in cancer development and progression. However, the regulatory roles and mechanisms of BRD7 in cancer metabolism are still unknown. In this study, we demonstrated that BRD7 was lowly expressed in breast cancer tissues and was identified as a poor prognostic factor in breast cancer. Meanwhile, BRD7 could suppress cell proliferation, initiate cell apoptosis and reduce aerobic glycolysis, suggesting that BRD7 plays a tumor suppressive roles in breast cancer. Mechanistically, BRD7 could negatively regulate a critical glycolytic enzyme LDHA through directly interaction with its upstream transcription factor, HIF1α, facilitating degradation of HIF1α mediated by ubiquitin-proteasome pathway. Moreover, restoring the expression of LDHA in breast cancer cells could reverse the effect of BRD7 on aerobic glycolysis, cell proliferation, and tumor formation, as well as the expression of cell cycle and apopotosis related molecules such as cyclin D1, CDK4, P21, and c-PARP both in vitro and in vivo. Taken together, these results indicate that BRD7 acts as a tumor suppressor in breast cancer and represses the glycolysis and tumor progression through inactivation of HIF1α/LDHA transcription axis.

Monitoring the Durability Performance of Concrete in Nuclear Waste Containment. Technical Progress Report No. 3

International Nuclear Information System (INIS)

Ulm, Franz-Josef

2000-01-01

OAK-B135 Monitoring the Durability Performance of Concrete in Nuclear Waste Containment. Technical Progress Report No. 3(NOTE: Part II A item 1 indicates ''PAPER'', but a report is attached electronically)

Real-time motion analysis reveals cell directionality as an indicator of breast cancer progression.

Directory of Open Access Journals (Sweden)

Michael C Weiger

Full Text Available Cancer cells alter their migratory properties during tumor progression to invade surrounding tissues and metastasize to distant sites. However, it remains unclear how migratory behaviors differ between tumor cells of different malignancy and whether these migratory behaviors can be utilized to assess the malignant potential of tumor cells. Here, we analyzed the migratory behaviors of cell lines representing different stages of breast cancer progression using conventional migration assays or time-lapse imaging and particle image velocimetry (PIV to capture migration dynamics. We find that the number of migrating cells in transwell assays, and the distance and speed of migration in unconstrained 2D assays, show no correlation with malignant potential. However, the directionality of cell motion during 2D migration nicely distinguishes benign and tumorigenic cell lines, with tumorigenic cell lines harboring less directed, more random motion. Furthermore, the migratory behaviors of epithelial sheets observed under basal conditions and in response to stimulation with epidermal growth factor (EGF or lysophosphatitic acid (LPA are distinct for each cell line with regard to cell speed, directionality, and spatiotemporal motion patterns. Surprisingly, treatment with LPA promotes a more cohesive, directional sheet movement in lung colony forming MCF10CA1a cells compared to basal conditions or EGF stimulation, implying that the LPA signaling pathway may alter the invasive potential of MCF10CA1a cells. Together, our findings identify cell directionality as a promising indicator for assessing the tumorigenic potential of breast cancer cell lines and show that LPA induces more cohesive motility in a subset of metastatic breast cancer cells.

EPCR promotes breast cancer progression by altering SPOCK1/testican 1-mediated 3D growth

Directory of Open Access Journals (Sweden)

Naiara Perurena

2017-01-01

Full Text Available Abstract Background Activated protein C/endothelial protein C receptor (APC/EPCR axis is physiologically involved in anticoagulant and cytoprotective activities in endothelial cells. Emerging evidence indicates that EPCR also plays a role in breast stemness and human tumorigenesis. Yet, its contribution to breast cancer progression and metastasis has not been elucidated. Methods Transcriptomic status of EPCR was examined in a cohort of 286 breast cancer patients. Cell growth kinetics was evaluated in control and EPCR and SPARC/osteonectin, Cwcv, and kazal-like domains proteoglycan (SPOCK1/testican 1 silenced breast cancer cells in 2D, 3D, and in co-culture conditions. Orthotopic tumor growth and lung and osseous metastases were evaluated in several human and murine xenograft breast cancer models. Tumor-stroma interactions were further studied in vivo by immunohistochemistry and flow cytometry. An EPCR-induced gene signature was identified by microarray analysis. Results Analysis of a cohort of breast cancer patients revealed an association of high EPCR levels with adverse clinical outcome. Interestingly, EPCR knockdown did not affect cell growth kinetics in 2D but significantly reduced cell growth in 3D cultures. Using several human and murine xenograft breast cancer models, we showed that EPCR silencing reduced primary tumor growth and secondary outgrowths at metastatic sites, including the skeleton and the lungs. Interestingly, these effects were independent of APC ligand stimulation in vitro and in vivo. Transcriptomic analysis of EPCR-silenced tumors unveiled an effect mediated by matricellular secreted proteoglycan SPOCK1/testican 1. Interestingly, SPOCK1 silencing suppressed in vitro 3D growth. Moreover, SPOCK1 ablation severely decreased orthotopic tumor growth and reduced bone metastatic osteolytic tumors. High SPOCK1 levels were also associated with poor clinical outcome in a subset breast cancer patients. Our results suggest that EPCR

Total Factor Productivity Growth, Technical Progress & Efficiency Change in Vietnam Coal Industry - Nonparametric Approach

Science.gov (United States)

Phuong, Vu Hung

2018-03-01

This research applies Data Envelopment Analysis (DEA) approach to analyze Total Factor Productivity (TFP) and efficiency changes in Vietnam coal mining industry from 2007 to 2013. The TFP of Vietnam coal mining companies decreased due to slow technological progress and unimproved efficiency. The decadence of technical efficiency in many enterprises proved that the coal mining industry has a large potential to increase productivity through technical efficiency improvement. Enhancing human resource training, technology and research & development investment could help the industry to improve efficiency and productivity in Vietnam coal mining industry.

Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis.

Science.gov (United States)

Yardley, Denise A; Noguchi, Shinzaburo; Pritchard, Kathleen I; Burris, Howard A; Baselga, José; Gnant, Michael; Hortobagyi, Gabriel N; Campone, Mario; Pistilli, Barbara; Piccart, Martine; Melichar, Bohuslav; Petrakova, Katarina; Arena, Francis P; Erdkamp, Frans; Harb, Wael A; Feng, Wentao; Cahana, Ayelet; Taran, Tetiana; Lebwohl, David; Rugo, Hope S

2013-10-01

Effective treatments for hormone-receptor-positive (HR(+)) breast cancer (BC) following relapse/progression on nonsteroidal aromatase inhibitor (NSAI) therapy are needed. Initial Breast Cancer Trials of OraL EveROlimus-2 (BOLERO-2) trial data demonstrated that everolimus and exemestane significantly prolonged progression-free survival (PFS) versus placebo plus exemestane alone in this patient population. BOLERO-2 is a phase 3, double-blind, randomized, international trial comparing everolimus (10 mg/day) plus exemestane (25 mg/day) versus placebo plus exemestane in postmenopausal women with HR(+) advanced BC with recurrence/progression during or after NSAIs. The primary endpoint was PFS by local investigator review, and was confirmed by independent central radiology review. Overall survival, response rate, and clinical benefit rate were secondary endpoints. Final study results with median 18-month follow-up show that median PFS remained significantly longer with everolimus plus exemestane versus placebo plus exemestane [investigator review: 7.8 versus 3.2 months, respectively; hazard ratio = 0.45 (95% confidence interval 0.38-0.54); log-rank P NSAIs. These results further support the use of everolimus plus exemestane in this patient population. ClinicalTrials.gov #NCT00863655.

Sludge Treatment Evaluation: 1992 Technical progress

International Nuclear Information System (INIS)

Silva, L.J.; Felmy, A.R.; Ding, E.R.

1993-01-01

This report documents Fiscal Year 1992 technical progress on the Sludge Treatment Evaluation Task, which is being conducted by Pacific Northwest Laboratory. The objective of this task is to develop a capability to predict the performance of pretreatment processes for mixed radioactive and hazardous waste stored at Hanford and other US Department of Energy (DOE) sites. Significant cost savings can be achieved if radionuclides and other undesirable constituents can be effectively separated from the bulk waste prior to final treatment and disposal. This work is initially focused on chemical equilibrium prediction of water washing and acid or base dissolution of Hanford single-shell tank (SST) sludges, but may also be applied to other steps in pretreatment processes or to other wastes. Although SST wastes contain many chemical species, there are relatively few constituents -- Na, Al, NO 3 , NO 2 , PO 4 , SO 4 , and F -- contained in the majority of the waste. These constituents comprise 86% and 74% of samples from B-110 and U-110 SSTS, respectively. The major radionuclides of interest (Cs, Sr, Tc, U) are present in the sludge in small molal quantities. For these constituents, and other important components that are present in small molal quantities, the specific ion-interaction terms used in the Pitzer or NRTL equations may be assumed to be zero for a first approximation. Model development can also be accelerated by considering only the acid or base conditions that apply for the key pretreatment steps. This significantly reduces the number of chemical species and chemical reactions that need to be considered. Therefore, significant progress can be made by developing all the specific ion interactions for a base model and an acid dissolution model

Sludge Treatment Evaluation: 1992 Technical progress

Energy Technology Data Exchange (ETDEWEB)

Silva, L J; Felmy, A R; Ding, E R

1993-01-01

This report documents Fiscal Year 1992 technical progress on the Sludge Treatment Evaluation Task, which is being conducted by Pacific Northwest Laboratory. The objective of this task is to develop a capability to predict the performance of pretreatment processes for mixed radioactive and hazardous waste stored at Hanford and other US Department of Energy (DOE) sites. Significant cost savings can be achieved if radionuclides and other undesirable constituents can be effectively separated from the bulk waste prior to final treatment and disposal. This work is initially focused on chemical equilibrium prediction of water washing and acid or base dissolution of Hanford single-shell tank (SST) sludges, but may also be applied to other steps in pretreatment processes or to other wastes. Although SST wastes contain many chemical species, there are relatively few constituents -- Na, Al, NO[sub 3], NO[sub 2], PO[sub 4], SO[sub 4], and F -- contained in the majority of the waste. These constituents comprise 86% and 74% of samples from B-110 and U-110 SSTS, respectively. The major radionuclides of interest (Cs, Sr, Tc, U) are present in the sludge in small molal quantities. For these constituents, and other important components that are present in small molal quantities, the specific ion-interaction terms used in the Pitzer or NRTL equations may be assumed to be zero for a first approximation. Model development can also be accelerated by considering only the acid or base conditions that apply for the key pretreatment steps. This significantly reduces the number of chemical species and chemical reactions that need to be considered. Therefore, significant progress can be made by developing all the specific ion interactions for a base model and an acid dissolution model.

Trastuzumab beyond progression: overall survival analysis of the GBG 26/BIG 3-05 phase III study in HER2-positive breast cancer

DEFF Research Database (Denmark)

von Minckwitz, Gunter; Schwedler, Kathrin; Schmidt, Marcus

2011-01-01

Continuation of trastuzumab plus capecitabine (XH) showed a significantly improved overall response rate and time to progression compared with capecitabine (X) alone in women with HER2-positive breast cancer progressing during trastuzumab treatment. Here, we report the final analysis on overall...

Decontamination Systems Information and Research Program. Quarterly technical progress report, January 1--March 31, 1994

Energy Technology Data Exchange (ETDEWEB)

1994-05-01

West Virginia University (WVU) and the US DOE Morgantown Energy Technology Center (METC) entered into a Cooperative Agreement on August 29, 1992 entitled ``Decontamination Systems Information and Research Programs.`` Stipulated within the Agreement is the requirement that WVU submit to METC a series of Technical Progress Reports on a quarterly basis. This report comprises the first Quarterly Technical Progress Report for Year 2 of the Agreement. This report reflects the progress and/or efforts performed on the sixteen (16) technical projects encompassed by the Year 2 Agreement for the period of January 1 through March 31, 1994. In situ bioremediation of chlorinated organic solvents; Microbial enrichment for enhancing in-situ biodegradation of hazardous organic wastes; Treatment of volatile organic compounds (VOCs) using biofilters; Drain-enhanced soil flushing (DESF) for organic contaminants removal; Chemical destruction of chlorinated organic compounds; Remediation of hazardous sites with steam reforming; Soil decontamination with a packed flotation column; Use of granular activated carbon columns for the simultaneous removal of organics, heavy metals, and radionuclides; Monolayer and multilayer self-assembled polyion films for gas-phase chemical sensors; Compact mercuric iodide detector technology development; Evaluation of IR and mass spectrometric techniques for on-site monitoring of volatile organic compounds; A systematic database of the state of hazardous waste clean-up technologies; Dust control methods for insitu nuclear and hazardous waste handling; Winfield Lock and Dam remediation; and Socio-economic assessment of alternative environmental restoration technologies.

Environmental Research Division technical progress report, January 1984-December 1985

International Nuclear Information System (INIS)

1986-05-01

Technical progress in the various research and assessment activities of Argonne National Laboratory's Environmental Research Division is reported for the period 1984 to 1985. Textual, graphic, and tabular information is used to briefly summarize (in separate chapters) the work of the Division's Atmospheric Physics, Environmental Effects Research, Environmental Impacts, Fundamental Molecular Physics and Chemistry, and Waste Management Programs. Information on professional qualifications, awards, and outstanding professional activities of staff members, as well as lists of publications, oral presentations, special events organized, and participants in educational programs, are provided in appendices at the end of each chapter

Environmental Research Division technical progress report, January 1984-December 1985

Energy Technology Data Exchange (ETDEWEB)

1986-05-01

Technical progress in the various research and assessment activities of Argonne National Laboratory's Environmental Research Division is reported for the period 1984 to 1985. Textual, graphic, and tabular information is used to briefly summarize (in separate chapters) the work of the Division's Atmospheric Physics, Environmental Effects Research, Environmental Impacts, Fundamental Molecular Physics and Chemistry, and Waste Management Programs. Information on professional qualifications, awards, and outstanding professional activities of staff members, as well as lists of publications, oral presentations, special events organized, and participants in educational programs, are provided in appendices at the end of each chapter.

Data on the putative role of p53 in breast cancer cell adhesion: Technical information for adhesion assay

Directory of Open Access Journals (Sweden)

Kallirroi Voudouri

2016-12-01

Full Text Available In this data article, the potential role of p53 tumor suppressor gene (p53 on the attachment ability of MCF-7 breast cancer cells was investigated. In our main article, “IGF-I/ EGF and E2 signaling crosstalk through IGF-IR conduit point affect breast cancer cell adhesion” (K. Voudouri, D. Nikitovic, A. Berdiaki, D. Kletsas, N.K. Karamanos, G.N. Tzanakakis, 2016 [1], we describe the key role of IGF-IR in breast cancer cell adhesion onto fibronectin (FN. p53 tumor suppressor gene is a principal regulator of cancer cell proliferation. Various data have demonstrated an association between p53 and IGF-IR actions on cell growth through its’ putative regulation of IGF-IR expression. According to our performed experiments, p53 does not modify IGF-IR expression and does not affect basal MCF-7 cells adhesion onto FN. Moreover, technical details about the performance of adhesion assay onto the FN substrate were provided.

N-heterocyclic carbene complexes of silver and gold as novel tools against breast cancer progression.

Science.gov (United States)

Saturnino, Carmela; Barone, Ines; Iacopetta, Domenico; Mariconda, Annaluisa; Sinicropi, Maria Stefania; Rosano, Camillo; Campana, Antonella; Catalano, Stefania; Longo, Pasquale; Andò, Sebastiano

2016-12-01

Metal carbenic complexes have received considerable attention in both the catalysis and biological fields for their potential applications in cancer and antimicrobial therapies. A small series of new silver and gold N-heterocyclic carbene complexes has been designed and synthesized. Among the tested complexes, one compound was particularly active in inhibiting anchorage-dependent and -independent breast cancer proliferation, and inducing cell apoptosis via a mitochondria-related process. The antitumor activity was associated to the transcriptional activation of the tumor suppressor gene p53 in an Sp1-dependent manner, as evidenced by biological and docking studies. Our results highlight the importance and the versatility of N-heterocyclic carbene complexes of gold and silver as useful tools against breast cancer progression.

Institutional effectiveness of REDD+ MRV: Countries progress in implementing technical guidelines and good governance requirements

NARCIS (Netherlands)

Ochieng, R.M.; Visseren-Hamakers, Ingrid; Arts, B.; Brockhaus, M.; Herold, M.

2016-01-01

The UNFCCC requires REDD+ countries wishing to receive results-based payments to measure, report and verify (MRV) REDD+ impacts; and outlines technical guidelines and good governance requirements for MRV. This article examines institutional effectiveness of REDD+ MRV by assessing countries’ progress

Mammography density estimation with automated volumetic breast density measurement

International Nuclear Information System (INIS)

Ko, Su Yeon; Kim, Eun Kyung; Kim, Min Jung; Moon, Hee Jung

2014-01-01

To compare automated volumetric breast density measurement (VBDM) with radiologists' evaluations based on the Breast Imaging Reporting and Data System (BI-RADS), and to identify the factors associated with technical failure of VBDM. In this study, 1129 women aged 19-82 years who underwent mammography from December 2011 to January 2012 were included. Breast density evaluations by radiologists based on BI-RADS and by VBDM (Volpara Version 1.5.1) were compared. The agreement in interpreting breast density between radiologists and VBDM was determined based on four density grades (D1, D2, D3, and D4) and a binary classification of fatty (D1-2) vs. dense (D3-4) breast using kappa statistics. The association between technical failure of VBDM and patient age, total breast volume, fibroglandular tissue volume, history of partial mastectomy, the frequency of mass > 3 cm, and breast density was analyzed. The agreement between breast density evaluations by radiologists and VBDM was fair (k value = 0.26) when the four density grades (D1/D2/D3/D4) were used and moderate (k value = 0.47) for the binary classification (D1-2/D3-4). Twenty-seven women (2.4%) showed failure of VBDM. Small total breast volume, history of partial mastectomy, and high breast density were significantly associated with technical failure of VBDM (p 0.001 to 0.015). There is fair or moderate agreement in breast density evaluation between radiologists and VBDM. Technical failure of VBDM may be related to small total breast volume, a history of partial mastectomy, and high breast density.

Index to Nuclear Safety: a technical progress review by chrology, permuted title, and author, Volume 11(1) through Volume 20(6)

Energy Technology Data Exchange (ETDEWEB)

Cottrell, W B; Passiakos, M

1980-06-01

This index to Nuclear Safety, a bimonthly technical progress review, covers articles published in Nuclear Safety, Volume II, No. 1 (January-February 1970), through Volume 20, No. 6 (November-December 1979). It is divided into three sections: a chronological list of articles (including abstracts) followed by a permuted-title (KWIC) index and an author index. Nuclear Safety, a bimonthly technical progress review prepared by the Nuclear Safety Information Center (NSIC), covers all safety aspects of nuclear power reactors and associated facilities. Over 600 technical articles published in Nuclear Safety in the last ten years are listed in this index.

Neoplastic and stromal cells contribute to an extracellular matrix gene expression profile defining a breast cancer subtype likely to progress.

Directory of Open Access Journals (Sweden)

Tiziana Triulzi

Full Text Available We recently showed that differential expression of extracellular matrix (ECM genes delineates four subgroups of breast carcinomas (ECM1, -2, -3- and -4 with different clinical outcome. To further investigate the characteristics of ECM signature and its impact on tumor progression, we conducted unsupervised clustering analyses in 6 additional independent datasets of invasive breast tumors from different platforms for a total of 643 samples. Use of four different clustering algorithms identified ECM3 tumors as an independent group in all datasets tested. ECM3 showed a homogeneous gene pattern, consisting of 58 genes encoding 43 structural ECM proteins. From 26 to 41% of the cases were ECM3-enriched, and analysis of datasets relevant to gene expression in neoplastic or corresponding stromal cells showed that both stromal and breast carcinoma cells can coordinately express ECM3 genes. In in vitro experiments, β-estradiol induced ECM3 gene production in ER-positive breast carcinoma cell lines, whereas TGFβ induced upregulation of the genes leading to ECM3 gene classification, especially in ER-negative breast carcinoma cells and in fibroblasts. Multivariate analysis of distant metastasis-free survival in untreated breast tumor patients revealed a significant interaction between ECM3 and histological grade (p = 0.001. Cox models, estimated separately in grade I-II and grade III tumors, indicated a highly significant association between ECM3 and worse survival probability only in grade III tumors (HR = 3.0, 95% CI = 1.3-7.0, p = 0.0098. Gene Set Enrichment analysis of ECM3 compared to non-ECM3 tumors revealed significant enrichment of epithelial-mesenchymal transition (EMT genes in both grade I-II and grade III subsets of ECM3 tumors. Thus, ECM3 is a robust cluster that identifies breast carcinomas with EMT features but with accelerated metastatic potential only in the undifferentiated (grade III phenotype. These findings support the

A seven-gene CpG-island methylation panel predicts breast cancer progression

International Nuclear Information System (INIS)

Li, Yan; Melnikov, Anatoliy A.; Levenson, Victor; Guerra, Emanuela; Simeone, Pasquale; Alberti, Saverio; Deng, Youping

2015-01-01

DNA methylation regulates gene expression, through the inhibition/activation of gene transcription of methylated/unmethylated genes. Hence, DNA methylation profiling can capture pivotal features of gene expression in cancer tissues from patients at the time of diagnosis. In this work, we analyzed a breast cancer case series, to identify DNA methylation determinants of metastatic versus non-metastatic tumors. CpG-island methylation was evaluated on a 56-gene cancer-specific biomarker microarray in metastatic versus non-metastatic breast cancers in a multi-institutional case series of 123 breast cancer patients. Global statistical modeling and unsupervised hierarchical clustering were applied to identify a multi-gene binary classifier with high sensitivity and specificity. Network analysis was utilized to quantify the connectivity of the identified genes. Seven genes (BRCA1, DAPK1, MSH2, CDKN2A, PGR, PRKCDBP, RANKL) were found informative for prognosis of metastatic diffusion and were used to calculate classifier accuracy versus the entire data-set. Individual-gene performances showed sensitivities of 63–79 %, 53–84 % specificities, positive predictive values of 59–83 % and negative predictive values of 63–80 %. When modelled together, these seven genes reached a sensitivity of 93 %, 100 % specificity, a positive predictive value of 100 % and a negative predictive value of 93 %, with high statistical power. Unsupervised hierarchical clustering independently confirmed these findings, in close agreement with the accuracy measurements. Network analyses indicated tight interrelationship between the identified genes, suggesting this to be a functionally-coordinated module, linked to breast cancer progression. Our findings identify CpG-island methylation profiles with deep impact on clinical outcome, paving the way for use as novel prognostic assays in clinical settings. The online version of this article (doi:10.1186/s12885-015-1412-9) contains supplementary

Nonequilibrium photochemical reactions induced by lasers. Technical progress report

International Nuclear Information System (INIS)

Steinfeld, J.I.

1978-04-01

Research has progressed in six principal subject areas of interest to DOE advanced (laser) isotope separation efforts. These are (1) Infrared double resonance spectroscopy of molecules excited by multiple infrared photon absorption, particularly SF 6 and vinyl chloride. (2) Infrared multiphoton excitation of metastable triplet-state molecules, e.g., biacetyl. (3) An Information Theory analysis of multiphoton excitation and collisional deactivation has been carried out. (4) The mechanism of infrared energy deposition and multiphoton-induced reactions in chlorinated ethylene derivatives; and RRKM (statistical) model accounts for all observed behavior of the system, and a deuterium-specific reaction pathway has been identified. (5) Diffusion-enhanced laser isotope separation in N 16 O/N 18 O. (6) A technical evaluation of laser-induced chemistry and isotope separation

Projects at the component development and integration facility. Quarterly technical progress report, April 1, 1994--June 30, 1994

International Nuclear Information System (INIS)

1994-01-01

This quarterly technical progress report presents progress on the projects at the Component Development and Integration Facility (CDIF) during the third quarter of FY94. The CDIF is a major Department of Energy test facility in Butte, Montana, operated by MSE, Inc. Projects in progress include: Biomass Remediation Project; Heavy Metal-Contaminated Soil Project; MHD Shutdown; Mine Waste Technology Pilot Program; Plasma Projects; Resource Recovery Project; and Spray Casting Project

Progress in diagnosis of breast cancer: Advances in radiology technology

Directory of Open Access Journals (Sweden)

J Mari Beth Linder

2015-01-01

Full Text Available Breast cancer is the leading cause of cancer in females between the ages of 15 and 54, and the second leading cause of cancer death in women in the United States. Diagnosis begins with detection by breast examination (clinical breast exam or breast self-exam or by radiologic studies, like mammography. Many advances in the diagnosis of breast cancer have taken place in recent years. This article will review the history of radiologic advances in the diagnosis of breast cancer. Use of technological advancements in digital breast tomosynthesis, magnetic resonance imaging, and ultrasound in breast cancer diagnosis will be presented. Advantages and disadvantages of these diagnostic interventions when compared to older, traditional X-ray films will be discussed. It is important for all nurses, including radiology and oncology nurses, to be well informed about these varied diagnostic modalities, and appreciate the fact that advances in radiologic imaging technologies can yield improved outcomes for breast cancer patients.

Limited utility of tissue micro-arrays in detecting intra-tumoral heterogeneity in stem cell characteristics and tumor progression markers in breast cancer.

Science.gov (United States)

Kündig, Pascale; Giesen, Charlotte; Jackson, Hartland; Bodenmiller, Bernd; Papassotirolopus, Bärbel; Freiberger, Sandra Nicole; Aquino, Catharine; Opitz, Lennart; Varga, Zsuzsanna

2018-05-08

Intra-tumoral heterogeneity has been recently addressed in different types of cancer, including breast cancer. A concept describing the origin of intra-tumoral heterogeneity is the cancer stem-cell hypothesis, proposing the existence of cancer stem cells that can self-renew limitlessly and therefore lead to tumor progression. Clonal evolution in accumulated single cell genomic alterations is a further possible explanation in carcinogenesis. In this study, we addressed the question whether intra-tumoral heterogeneity can be reliably detected in tissue-micro-arrays in breast cancer by comparing expression levels of conventional predictive/prognostic tumor markers, tumor progression markers and stem cell markers between central and peripheral tumor areas. We analyzed immunohistochemical expression and/or gene amplification status of conventional prognostic tumor markers (ER, PR, HER2, CK5/6), tumor progression markers (PTEN, PIK3CA, p53, Ki-67) and stem cell markers (mTOR, SOX2, SOX9, SOX10, SLUG, CD44, CD24, TWIST) in 372 tissue-micro-array samples from 72 breast cancer patients. Expression levels were compared between central and peripheral tumor tissue areas and were correlated to histopathological grading. 15 selected cases additionally underwent RNA sequencing for transcriptome analysis. No significant difference in any of the analyzed between central and peripheral tumor areas was seen with any of the analyzed methods/or results that showed difference. Except mTOR, PIK3CA and SOX9 (nuclear) protein expression, all markers correlated significantly (p < 0.05) with histopathological grading both in central and peripheral areas. Our results suggest that intra-tumoral heterogeneity of stem-cell and tumor-progression markers cannot be reliably addressed in tissue-micro-array samples in breast cancer. However, most markers correlated strongly with histopathological grading confirming prognostic information as expression profiles were independent on the site of the

The Gαh-PLCδ1 signaling axis drives metastatic progression in triple-negative breast cancer.

Science.gov (United States)

Huang, Shang-Pen; Liu, Pei-Yao; Kuo, Chih-Jung; Chen, Chi-Long; Lee, Wei-Jiunn; Tsai, Yu-Hui; Lin, Yuan-Feng

2017-06-02

Distant metastasis of triple-negative breast cancer (TNBC) to other organs, e.g., the lungs, has been correlated with poor survival rates among breast cancer patients. Therefore, the identification of useful therapeutic targets to prevent metastasis or even inhibit tumor growth of TNBC is urgently needed. Gαh is a novel GTP-binding protein and known as an inactive form of calcium-dependent tissue transglutaminase. However, the functional consequences of transamidating and G-protein activities of tissue transglutaminase in promoting cancer metastasis are still controversial. Kaplan-Meier analyses were performed to estimate the prognostic values of Gαh and PLCδ1 by utilizing public databases and performing immunohistochemical staining experiments. Cell-based invasion assays and in vivo lung colony-forming and orthotropic lung metastasis models were established to evaluate the effectiveness of interrupting the protein-protein interaction (PPI) between Gαh and PLCδ1 in inhibiting the invasive ability and metastatic potential of TNBC cells. Here, we showed that the increased level of cytosolic, not extracellular, Gαh is a poor prognostic marker in breast cancer patients and correlates with the metastatic evolution of TNBC cells. Moreover, clinicopathological analyses revealed that the combined signature of high Gαh/PLCδ1 levels indicates worse prognosis in patients with breast cancer and correlates with lymph node metastasis of ER-negative breast cancer. Blocking the PPI of the Gαh/PLCδ1 complex by synthetically myristoylated PLCδ1 peptide corresponding to the Gαh-binding interface appeared to significantly suppress cellular invasiveness in vitro and inhibit lung metastatic colonies of TNBC cells in vivo. This study establishes Gαh/PLCδ1 as a poor prognostic factor for patients with estrogen receptor-negative breast cancers, including TNBCs, and provides therapeutic value by targeting the PPI of the Gαh/PLCδ1 complex to combat the metastatic progression

Modeling the impacts of climate change and technical progress on the wheat yield in inland China: An autoregressive distributed lag approach.

Science.gov (United States)

Zhai, Shiyan; Song, Genxin; Qin, Yaochen; Ye, Xinyue; Lee, Jay

2017-01-01

This study aims to evaluate the impacts of climate change and technical progress on the wheat yield per unit area from 1970 to 2014 in Henan, the largest agricultural province in China, using an autoregressive distributed lag approach. The bounded F-test for cointegration among the model variables yielded evidence of a long-run relationship among climate change, technical progress, and the wheat yield per unit area. In the long run, agricultural machinery and fertilizer use both had significantly positive impacts on the per unit area wheat yield. A 1% increase in the aggregate quantity of fertilizer use increased the wheat yield by 0.19%. Additionally, a 1% increase in machine use increased the wheat yield by 0.21%. In contrast, precipitation during the wheat growth period (from emergence to maturity, consisting of the period from last October to June) led to a decrease in the wheat yield per unit area. In the short run, the coefficient of the aggregate quantity of fertilizer used was negative. Land size had a significantly positive impact on the per unit area wheat yield in the short run. There was no significant short-run or long-run impact of temperature on the wheat yield per unit area in Henan Province. The results of our analysis suggest that climate change had a weak impact on the wheat yield, while technical progress played an important role in increasing the wheat yield per unit area. The results of this study have implications for national and local agriculture policies under climate change. To design well-targeted agriculture adaptation policies for the future and to reduce the adverse effects of climate change on the wheat yield, climate change and technical progress factors should be considered simultaneously. In addition, adaptive measures associated with technical progress should be given more attention.

Modeling the impacts of climate change and technical progress on the wheat yield in inland China: An autoregressive distributed lag approach.

Directory of Open Access Journals (Sweden)

Shiyan Zhai

Full Text Available This study aims to evaluate the impacts of climate change and technical progress on the wheat yield per unit area from 1970 to 2014 in Henan, the largest agricultural province in China, using an autoregressive distributed lag approach. The bounded F-test for cointegration among the model variables yielded evidence of a long-run relationship among climate change, technical progress, and the wheat yield per unit area. In the long run, agricultural machinery and fertilizer use both had significantly positive impacts on the per unit area wheat yield. A 1% increase in the aggregate quantity of fertilizer use increased the wheat yield by 0.19%. Additionally, a 1% increase in machine use increased the wheat yield by 0.21%. In contrast, precipitation during the wheat growth period (from emergence to maturity, consisting of the period from last October to June led to a decrease in the wheat yield per unit area. In the short run, the coefficient of the aggregate quantity of fertilizer used was negative. Land size had a significantly positive impact on the per unit area wheat yield in the short run. There was no significant short-run or long-run impact of temperature on the wheat yield per unit area in Henan Province. The results of our analysis suggest that climate change had a weak impact on the wheat yield, while technical progress played an important role in increasing the wheat yield per unit area. The results of this study have implications for national and local agriculture policies under climate change. To design well-targeted agriculture adaptation policies for the future and to reduce the adverse effects of climate change on the wheat yield, climate change and technical progress factors should be considered simultaneously. In addition, adaptive measures associated with technical progress should be given more attention.

Hypofractionated Adjuvant Whole Breast Radiotherapy: Progress and Prospects

International Nuclear Information System (INIS)

Yarnold, John; Haviland, Joanne

2010-01-01

Published results of randomised trials involving >7000 women confirm the safety and efficacy of hypofractionated schedules of adjuvant radiotherapy for women with early breast cancer using fraction sizes between 2 and 3 Gy assuming appropriate downward adjustments to total dose. Unnecessary concerns relating to heart tolerance, suboptimal dose distribution and duration of follow up need not discourage the routine adoption of 15- or 16-fraction schedules in women treated by breast conservation surgery for early breast cancer. Regardless of fractionation regimen, dose escalation to the index quadrant in high risk subgroups will result in a greater relative increase in late adverse effects than tumour control, a therapeutic disadvantage that can only be overcome by exploiting a marked dose-volume effect. A 15-fraction schedule of whole breast radiotherapy is unlikely to represent the lower limits of hypofractionation, and the preliminary results of a 5-fraction regimen are encouraging

The Impacts of Technical Progress on Sulfur Dioxide Kuznets Curve in China: A Spatial Panel Data Approach

Directory of Open Access Journals (Sweden)

Zhimin Zhou

2017-04-01

Full Text Available This paper aims to reveal the nexus for sulfur dioxide (SO2 emission and income, as well as the effects of technical progress on SO2 emission in China based on environment Kuznets curve (EKC hypothesis. The spatial panel technique is used in case the coefficient estimates are biased due to the negligence of spatial dependence. With the provincial panel data of China from 2004 to 2014, this is the first research that finds an inverse N-trajectory of the relationship between SO2 emission and economic growth and confirms the beneficial impacts of technical advancement on SO2 emission abatement. The empirical results also suggest that the industrial structure change is an important driving force of the SO2 EKC. In addition, the direct and spillover effects of determinants on sulfur emission are clarified and estimated by a correct approach. Finally, we check the stability of our conclusions on the EKC shape for SO2 and technical progress effects when controlling for different variables and specifications, through which we find the turning points are sensitive to variables selections.

Technical progress and climatic change

International Nuclear Information System (INIS)

Ausubel, J.H.

1995-01-01

The global warming debate has neglected and thus underestimated the importance of technical change in considering reduction in greenhouse gases and adaptation to climate change. Relevant quantitative cases of long-run technical change during the past 100 years are presented in computing, communications, transport, energy, and agriculture. A noteworthy technological trajectory is that of decarbonization, or decreasing carbon intensity of primary energy. If human societies have not yet reached the end of the history of technology, the cost structure for mitigation and adaptation changes could be cheap. (Author)

Role of Protein Synthesis Initiation Factors in Dietary Soy Isoflavone-Mediated Effects on Breast Cancer Progression

Science.gov (United States)

2012-03-01

Manuscript s • Submitted to the Journal of Nutritional Biochemistry (Feb 21, 2012) “The soy isoflavone equol may increase cancer malignancy via upregulation...29] Ko KP, Park SK, Park B et al. Isoflavones from phytoestrogens and gastric cancer risk: a nested case-control study within the Korean...Dietary Soy Isoflavone-Mediated Effects on Breast Cancer Progression. PRINCIPAL INVESTIGATOR: Columba de la Parra Simental CONTRACTING

Western Research Institute: Annual technical progress report, October 1987--September 1988

Energy Technology Data Exchange (ETDEWEB)

1988-12-01

This report describes the technical progress made by the Western Research Institute of the University of Wyoming Research Institute of the University of Wyoming Research Corporation on work performed for the period October 1, 1987 through September 30, 1988. This research involves five resource areas: oil shale, tar sand, underground coal gasification, advanced process technology, and advanced fuels research. Under the terms of the cooperative agreement, an annual project plan has been approved by DOE. The work reported herein reflects the implementation of the research in the plan and follows the structure used therein. 49 refs., 32 figs., 87 tabs.

[Fluorine-18 labeled androgens and progestins; imaging agents for tumors of prostate and breast]: Technical progress report, February 1, 1987-January 31, 1988

International Nuclear Information System (INIS)

Katzenellenbogen, J.A.

1987-01-01

This project develops fluorine-18 labeled steroids that possess high binding affinity and selectivity for androgen and progesterone receptors and can be used as positron-emission tomographic imaging agents for prostate tumors and breast tumors, respectively. These novel diagnostic agents may enable an accurate estimation of tumor dissemination, such as metastasis of prostate cancer and lymph node involvement of breast cancer, and an in vivo determination of the endocrine responsiveness of these tumors. They will provide essential information for the selection of alternative therapies thereby improving the management of prostate and breast cancer patients. 14 refs., 1 tab

Development of a new technic for breast attenuation correction in myocardial perfusion scintigraphy using computational methods

International Nuclear Information System (INIS)

Oliveira, Anderson de

2015-01-01

Introduction: One of the limitations of nuclear medicine studies are false-positive results that lead to unnecessary exams and procedures associated to morbidity and costs to the individual and society. One of the most frequent causes for reducing the specificity of myocardial perfusion imaging (MPI) is photon attenuation, especially by breast in women. Objective: To develop a new technique to compensate the photon attenuation by women breasts in myocardial perfusion imaging with 99m Tc-sestamibi, using computational methods. Materials and methods: A procedure was proposed which integrates Monte Carlo simulation, computational methods and experimental techniques. Initially, were obtained the chest attenuation correction percentages using a phantom Jaszczak and breast attenuation percentages by Monte Carlo simulation method, using the EGS4 program. The percentages of attenuation correction were linked to individual patients' characteristics by an artificial neural network and a multivariate analysis. A preliminary technical validation was done by comparing the results of the MPI and catheterism (CAT), before and after applying the technique to 4 patients. The t test for parametric data, Wilcoxon, Mann-Whitney and X 2 for the others were used. Probability values less than 0.05 were considered statistically significant. Results: Each increment of 1 cm in the thickness of breast was associated to an average increment of 6% on photon attenuation, while the maximum increase related to breast composition was about 2%. The average chest attenuation percentage per unit was 2.9%. Both, the artificial neural network and linear regression, showed an error less than 3% as predictive models for percentage of female attenuation. The anatomical-functional correlation between MPI and CAT was maintained after the use of the technique. Conclusion: Results suggest that the proposed technique is promising and could be a possible alternative to other conventional methods employed

Technical meeting on progress in managing, and limiting the consequences of events exceeding the design basis

International Nuclear Information System (INIS)

Fabian, H.

2004-01-01

The Technical Groups on 'Reactor Safety' and 'Thermodynamics and Fluid Dynamics' of the Kerntechnische Gesellschaft e.V. organized a joint technical meeting on 'Progress in Managing, and Limiting the Consequences of, Events Exceeding the Design Basis' at the FTU Training Center of the Karlsruhe Research Center. The topic chosen, the papers presented, the presenters, and the non-technical part of the program met with lively interest on the part of institutions in the nuclear field. These were the objectives of the technical meeting: - Establishing a forum for communicating relevant topics. - In-depth discussion of the main topic, i.e. the advanced development of reactor safety, research in the field, and its application, in twenty selected papers presented by speakers from different institutions. - Presentation of topical work in a nuclear technology institution, the Karlsruhe Research Center. (orig.) [de

Studies in theoretical high energy particle physics: Technical progress report [February 1987-February 1988

International Nuclear Information System (INIS)

Sukhatme, U.P.; Keung, Wai-Yee; Kovacs, E.

1988-02-01

This is a technical progress report for grant No. FG02-84ER40173 for the period February 1987 to February 1988. Our research on supersymmetric quantum mechanics has yielded many interesting results. In particular, a systematic approach to the tunneling problem in double well potentials has been developed. Higgs boson related physics at the high energy hadron colliders has been extensively studied

HSP90 inhibition is effective in breast cancer: a phase II trial of tanespimycin (17-AAG) plus trastuzumab in patients with HER2-positive metastatic breast cancer progressing on trastuzumab.

Science.gov (United States)

Modi, Shanu; Stopeck, Alison; Linden, Hannah; Solit, David; Chandarlapaty, Sarat; Rosen, Neal; D'Andrea, Gabriella; Dickler, Maura; Moynahan, Mary E; Sugarman, Steven; Ma, Weining; Patil, Sujata; Norton, Larry; Hannah, Alison L; Hudis, Clifford

2011-08-01

HSP90 is a chaperone protein required for the stability of a variety of client proteins. 17-Demethoxygeldanamycin (17-AAG) is a natural product that binds to HSP90 and inhibits its activity, thereby inducing the degradation of these clients. In preclinical studies, HER2 is one of the most sensitive known client proteins of 17-AAG. On the basis of these data and activity in a phase I study, we conducted a phase II study of 17-AAG (tanespimycin) with trastuzumab in advanced trastuzumab-refractory HER2-positive breast cancer. We enrolled patients with metastatic HER2(+) breast cancer whose disease had previously progressed on trastuzumab. All patients received weekly treatment with tanespimycin at 450 mg/m(2) intravenously and trastuzumab at a conventional dose. Therapy was continued until disease progression. The primary endpoint was response rate by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Thirty-one patients were enrolled with a median age of 53 years and a median Karnofsky performance status (KPS) of 90%. The most common toxicities, largely grade 1, were diarrhea, fatigue, nausea, and headache. The overall response rate was 22%, the clinical benefit rate [complete response + partial response + stable disease] was 59%, the median progression-free survival was 6 months (95% CI: 4-9), and the median overall survival was 17 months (95% CI: 16-28). This is the first phase II study to definitively show RECIST-defined responses for 17-AAG in solid tumors. Tanespimycin plus trastuzumab has significant anticancer activity in patients with HER2-positive, metastatic breast cancer previously progressing on trastuzumab. Further research exploring this therapeutic interaction and the activity of HSP90 inhibitors is clearly warranted. ©2011 AACR.

Expression of cyclophilin B is associated with malignant progression and regulation of genes implicated in the pathogenesis of breast cancer.

Science.gov (United States)

Fang, Feng; Flegler, Ayanna J; Du, Pan; Lin, Simon; Clevenger, Charles V

2009-01-01

Cyclophilin B (CypB) is a 21-kDa protein with peptidyl-prolyl cis-trans isomerase activity that functions as a transcriptional inducer for Stat5 and as a ligand for CD147. To better understand the global function of CypB in breast cancer, T47D cells with a small interfering RNA-mediated knockdown of CypB were generated. Subsequent expression profiling analysis showed that 663 transcripts were regulated by CypB knockdown, and that many of these gene products contributed to cell proliferation, cell motility, and tumorigenesis. Real-time PCR confirmed that STMN3, S100A4, S100A6, c-Myb, estrogen receptor alpha, growth hormone receptor, and progesterone receptor were all down-regulated in si-CypB cells. A linkage analysis of these array data to protein networks resulted in the identification of 27 different protein networks that were impacted by CypB knockdown. Functional assays demonstrated that CypB knockdown also decreased cell growth, proliferation, and motility. Immunohistochemical and immunofluorescent analyses of a matched breast cancer progression tissue microarray that was labeled with an anti-CypB antibody demonstrated a highly significant increase in CypB protein levels as a function of breast cancer progression. Taken together, these results suggest that the enhanced expression of CypB in malignant breast epithelium may contribute to the pathogenesis of this disease through its regulation of the expression of hormone receptors and gene products that are involved in cell proliferation and motility.

The role of technical progress in the process of recalculating oil reserves; Le role du progres technique dans le processus de renouvellement des reserves petrolieres

Energy Technology Data Exchange (ETDEWEB)

Boulard, J.N. [Total/Fina/Institut Francais du Petrole (IFP), 92 - Rueil-Malmaison (France)

1999-08-01

Contrary to the concept of resources (which is essentially a geological one), the notion of reserves designates the quantities that are technically and economically recoverable. Beyond the production-related effect, the reserves therefore evolve over time in accordance with numerous technical and economic parameters. Among these parameters, it can be seen that technical progress plays a considerable role throughout the process of converting resources into reserves, including progress in the identification, accessibility and processing of the resources, and improvements in economic viability. After having tackled the problem of measuring the 'technical progress effects' and citing examples, we demonstrate that the evolution in oil reserves is subject to three types of impact. These are a quantitative impact by significantly improving the recovery rates or making it possible to identify hitherto undetectable oil fields, a qualitative impact by widening the resource base thanks to the adoption of new categories of oil (in particular the so-called 'unconventional' oils) and by carrying out the gradual substitution between these resources of differing qualities. There is also a dynamic impact, through the acceleration of resource availability. Through these three approaches, technical progress makes makes it possible to ensure continuity in oil supply and contributes significantly to the recalculation of reserves. It therefore acts as a compensating factor, counterbalancing the progressive depletion of resources. (author)

Amarillo National Resource Center for Plutonium. Quarterly technical progress report, May 1--July 31, 1998

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-09-01

Progress is reported on research projects related to the following: Electronic resource library; Environment, safety, and health; Communication, education, training, and community involvement; Nuclear and other materials; and Reporting, evaluation, monitoring, and administration. Technical studies investigate remedial action of high explosives-contaminated lands, radioactive waste management, nondestructive assay methods, and plutonium processing, handling, and storage.

BREAST RECONSTRUCTIONS AFTER BREAST CANCER TREATING

Directory of Open Access Journals (Sweden)

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.

A new semiquantitative method for evaluation of metastasis progression.

Science.gov (United States)

Volarevic, A; Ljujic, B; Volarevic, V; Milovanovic, M; Kanjevac, T; Lukic, A; Arsenijevic, N

2012-01-01

Although recent technical advancements are directed toward developing novel assays and methods for detection of micro and macro metastasis, there are still no reports of reliable, simple to use imaging software that could be used for the detection and quantification of metastasis in tissue sections. We herein report a new semiquantitative method for evaluation of metastasis progression in a well established 4T1 orthotopic mouse model of breast cancer metastasis. The new semiquantitative method presented here was implemented by using the Autodesk AutoCAD 2012 program, a computer-aided design program used primarily for preparing technical drawings in 2 dimensions. By using the Autodesk AutoCAD 2012 software- aided graphical evaluation we managed to detect each metastatic lesion and we precisely calculated the average percentage of lung and liver tissue parenchyma with metastasis in 4T1 tumor-bearing mice. The data were highly specific and relevant to descriptive histological analysis, confirming reliability and accuracy of the AutoCAD 2012 software as new method for quantification of metastatic lesions. The new semiquantitative method using AutoCAD 2012 software provides a novel approach for the estimation of metastatic progression in histological tissue sections.

Xeroradiography of the breast

International Nuclear Information System (INIS)

Kalaf, J.M.

1977-01-01

Xeroradiography is a simple method of radiographic examination of the breast, it is readily interpreted, and with good technic xeroradiography can afford a more accurate identification of tumor calcifications and the periphery of the tumors. Xeroradiography of the breast must be faced as a complemental method and when associated with the informations of the medical history, the clinical examination and informations of other complemental methods will afford an effective evaluation of women with breast disease. (Author) [pt

Technical consideration of intact breast irradiation

International Nuclear Information System (INIS)

Buck, B.A.

1980-01-01

Alternatives to mastectomy in the treatment of breast cancer have been discussed in the medical literature since 1937. The advent of megavoltage equipment has enabled radiation therapy to become an increasingly accepted alternative. The modified treatment technique developed at the Joint Center for Radiation Therapy is discussed

Surgical resident technical skill self-evaluation: increased precision with training progression.

Science.gov (United States)

Quick, Jacob A; Kudav, Vishal; Doty, Jennifer; Crane, Megan; Bukoski, Alex D; Bennett, Bethany J; Barnes, Stephen L

2017-10-01

Surgical resident ability to accurately evaluate one's own skill level is an important part of educational growth. We aimed to determine if differences exist between self and observer technical skill evaluation of surgical residents performing a single procedure. We prospectively enrolled 14 categorical general surgery residents (six post-graduate year [PGY] 1-2, three PGY 3, and five PGY 4-5). Over a 6-month period, following each laparoscopic cholecystectomy, residents and seven faculty each completed the Objective Structured Assessment of Technical Skills (OSATS). Spearman's coefficient was calculated for three groups: senior (PGY 4-5), PGY3, and junior (PGY 1-2). Rho (ρ) values greater than 0.8 were considered well correlated. Of the 125 paired assessments (resident-faculty each evaluating the same case), 58 were completed for senior residents, 54 for PGY3 residents, and 13 for junior residents. Using the mean from all OSATS categories, trainee self-evaluations correlated well to faculty (senior ρ 0.97, PGY3 ρ 0.9, junior ρ 0.9). When specific OSATS categories were analyzed, junior residents exhibited poor correlation in categories of respect for tissue (ρ -0.5), instrument handling (ρ 0.71), operative flow (ρ 0.41), use of assistants (ρ 0.05), procedural knowledge (ρ 0.32), and overall comfort with the procedure (ρ 0.73). PGY3 residents lacked correlation in two OSATS categories, operative flow (ρ 0.7) and procedural knowledge (ρ 0.2). Senior resident self-evaluations exhibited strong correlations to observers in all areas. Surgical residents improve technical skill self-awareness with progressive training. Less-experienced trainees have a tendency to over-or-underestimate technical skill. Copyright © 2017 Elsevier Inc. All rights reserved.

Interleukin-19 in Breast Cancer

Directory of Open Access Journals (Sweden)

Ying-Yin Chen

2013-01-01

Full Text Available Inflammatory cytokines within the tumor microenvironment are linked to progression in breast cancer. Interleukin- (IL- 19, part of the IL-10 family, contributes to a range of diseases and disorders, such as asthma, endotoxic shock, uremia, psoriasis, and rheumatoid arthritis. IL-19 is expressed in several types of tumor cells, especially in squamous cell carcinoma of the skin, tongue, esophagus, and lung and invasive duct carcinoma of the breast. In breast cancer, IL-19 expression is correlated with increased mitotic figures, advanced tumor stage, higher metastasis, and poor survival. The mechanisms of IL-19 in breast cancer have recently been explored both in vitro and in vivo. IL-19 has an autocrine effect in breast cancer cells. It directly promotes proliferation and migration and indirectly provides a microenvironment for tumor progression, which suggests that IL-19 is a prognostic marker in breast cancer and that antagonizing IL-19 may have therapeutic potential.

Productivity Change, Technical Progress, and Relative Efficiency Change in the Public Accounting Industry

OpenAIRE

Rajiv D. Banker; Hsihui Chang; Ram Natarajan

2005-01-01

We present evidence on components of productivity change in the public accounting industry toward the end of the 20th century. Using revenue and human resource data from 64 of the 100 largest public accounting firms in the United States for the 1995--1999 period, we analyze productivity change, technical progress, and relative efficiency change over time. The average public accounting firm experienced a productivity growth of 9.5% between 1995 and 1999. We find support for the hypothesis that...

GPHS-RTGs in support of the Cassini RTG Program. Semi annual technical progress report, September 26, 1994--April 2, 1995

International Nuclear Information System (INIS)

1995-01-01

The technical progress achieved during the period 26 September 1994 through 2 April 1995 on Contract DE-AC03-91SF18852 Radioisotope Thermoelectric Generators and Ancillary Activities is described herein. Monthly technical activity for the period 27 February 1995 through 2 April 1995 is included in this progress report. The report addresses tasks, including: spacecraft integration and liaison; engineering support; safety; qualified unicouple production; ETG Fabrication, assembly, and test; ground support equipment; RTG shipping and launch support; designs, reviews, and mission applications; project management, quality assurance, reliability, contract changes, CAGO acquisition (operating funds), and CAGO maintenance and repair; and CAGO acquisition (capital funds)

Scatter radiation breast exposure during head CT: impact of scanning conditions and anthropometric parameters on shielded and unshielded breast dose

Energy Technology Data Exchange (ETDEWEB)

Klasic, B. [Hospital for pulmonary diseases, Zagreb (Croatia); Knezevic, Z.; Vekic, B. [Rudjer Boskovic Institute, Zagreb (Croatia); Brnic, Z.; Novacic, K. [Merkur Univ. Hospital, Zagreb (Croatia)

2006-07-01

Constantly increasing clinical requests for CT scanning of the head on our facility continue to raise concern regarding radiation exposure of patients, especially radiosensitive tissues positioned close to the scanning plane. The aim of our prospective study was to estimate scatter radiation doses to the breast from routine head CT scans, both with and without use of lead shielding, and to establish influence of various technical and anthropometric factors on doses using statistical data analysis. In 85 patient referred to head CT for objective medical reasons, one breast was covered with lead apron during CT scanning. Radiation doses were measured at skin of both breasts and over the apron simultaneously, by the use of thermo luminescent dosimeters. The doses showed a mean reduction by 37% due to lead shielding. After we statistically analyzed our data, we observed significant correlation between under-the-shield dose and values of technical parameters. We used multiple linear regression model to describe the relationships of doses to unshielded and shielded breast respectively, with anthropometric and technical factors. Our study proved lead shielding of the breast to be effective, easy to use and leading to a significant reduction in scatter dose. (author)

Scatter radiation breast exposure during head CT: impact of scanning conditions and anthropometric parameters on shielded and unshielded breast dose

International Nuclear Information System (INIS)

Klasic, B.; Knezevic, Z.; Vekic, B.; Brnic, Z.; Novacic, K.

2006-01-01

Constantly increasing clinical requests for CT scanning of the head on our facility continue to raise concern regarding radiation exposure of patients, especially radiosensitive tissues positioned close to the scanning plane. The aim of our prospective study was to estimate scatter radiation doses to the breast from routine head CT scans, both with and without use of lead shielding, and to establish influence of various technical and anthropometric factors on doses using statistical data analysis. In 85 patient referred to head CT for objective medical reasons, one breast was covered with lead apron during CT scanning. Radiation doses were measured at skin of both breasts and over the apron simultaneously, by the use of thermo luminescent dosimeters. The doses showed a mean reduction by 37% due to lead shielding. After we statistically analyzed our data, we observed significant correlation between under-the-shield dose and values of technical parameters. We used multiple linear regression model to describe the relationships of doses to unshielded and shielded breast respectively, with anthropometric and technical factors. Our study proved lead shielding of the breast to be effective, easy to use and leading to a significant reduction in scatter dose. (author)

Progression-free survival/time to progression as a potential surrogate for overall survival in HR+, HER2– metastatic breast cancer

Directory of Open Access Journals (Sweden)

Forsythe A

2018-05-01

Full Text Available Anna Forsythe,1 David Chandiwana,2 Janina Barth,3 Marroon Thabane,4 Johan Baeck,2 Gabriel Tremblay1 1Purple Squirrel Economics, New York, NY, 2Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 3Novartis Pharma GmbH, Nuremberg, Germany; 4Novartis Pharmaceuticals Incorporated, Dorval, QC, Canada Background: Several recent randomized controlled trials (RCTs in hormone receptor-positive (HR+, human epidermal growth factor receptor 2-negative (HER2– metastatic breast cancer (MBC have demonstrated significant improvements in progression-free survival (PFS; however, few have reported improvement in overall survival (OS. The surrogacy of PFS or time to progression (TTP for OS has not been formally investigated in HR+, HER2– MBC.Methods: A systematic literature review of RCTs in HR+, HER2– MBC was conducted to identify studies that reported both median PFS/TTP and OS. The correlation between PFS/TTP and OS was evaluated using Pearson’s product–moment correlation and Spearman’s rank correlation. Subgroup analyses were performed to explore possible reasons for heterogeneity. Errors-in-variables weighted least squares regression (LSR was used to model incremental OS months as a function of incremental PFS/TTP months. An exploratory analysis investigated the impact of three covariates (chemotherapy vs hormonal/targeted therapy, PFS vs TTP, and first-line therapy vs second-line therapy or greater on OS prediction. The lower 95% prediction band was used to determine the minimum incremental PFS/TTP months required to predict OS benefit (surrogate threshold effect [STE].Results: Forty studies were identified. There was a statistically significant correlation between median PFS/TTP and OS (Pearson =0.741, P=0.000; Spearman =0.650, P=0.000. These results proved consistent for chemotherapy and hormonal/targeted therapy. Univariate LSR analysis yielded an R2 of 0.354 with 1 incremental PFS/TTP month corresponding to 1.13 incremental OS months

A case report of locally advanced triple negative breast cancer showing pathological complete response to weekly paclitaxel with bevacizumab treatment following disease progression during anthracycline-based neoadjuvant chemotherapy

Directory of Open Access Journals (Sweden)

Hideo Shigematsu

2017-01-01

Conclusions: Although the addition of bevacizumab to standard adjuvant chemotherapy is not recommended in unselected triple negative breast cancer, the potent effect on tumor shrinkage should be considered in the treatment of locally advanced triple negative breast cancer showing disease progression during standard NAC.

Works Technical Department progress report, March 1961

Energy Technology Data Exchange (ETDEWEB)

None

1961-04-19

This document details the activities of the Savannah River Works Technical Department during the month of March 1961. Topics discussed are: Reactor Technology, Separations Technology, Engineering Assistance, Health Physics, Laboratories Overview, and Technical Papers Issued.

Chapter 27 -- Breast Cancer Genomics, Section VI, Pathology and Biological Markers of Invasive Breast Cancer

Energy Technology Data Exchange (ETDEWEB)

Spellman, Paul T.; Heiser, Laura; Gray, Joe W.

2009-06-18

Breast cancer is predominantly a disease of the genome with cancers arising and progressing through accumulation of aberrations that alter the genome - by changing DNA sequence, copy number, and structure in ways that that contribute to diverse aspects of cancer pathophysiology. Classic examples of genomic events that contribute to breast cancer pathophysiology include inherited mutations in BRCA1, BRCA2, TP53, and CHK2 that contribute to the initiation of breast cancer, amplification of ERBB2 (formerly HER2) and mutations of elements of the PI3-kinase pathway that activate aspects of epidermal growth factor receptor (EGFR) signaling and deletion of CDKN2A/B that contributes to cell cycle deregulation and genome instability. It is now apparent that accumulation of these aberrations is a time-dependent process that accelerates with age. Although American women living to an age of 85 have a 1 in 8 chance of developing breast cancer, the incidence of cancer in women younger than 30 years is uncommon. This is consistent with a multistep cancer progression model whereby mutation and selection drive the tumor's development, analogous to traditional Darwinian evolution. In the case of cancer, the driving events are changes in sequence, copy number, and structure of DNA and alterations in chromatin structure or other epigenetic marks. Our understanding of the genetic, genomic, and epigenomic events that influence the development and progression of breast cancer is increasing at a remarkable rate through application of powerful analysis tools that enable genome-wide analysis of DNA sequence and structure, copy number, allelic loss, and epigenomic modification. Application of these techniques to elucidation of the nature and timing of these events is enriching our understanding of mechanisms that increase breast cancer susceptibility, enable tumor initiation and progression to metastatic disease, and determine therapeutic response or resistance. These studies also

Role of DNA Methylation in Altering Gene Expression During the Early Stages of Human Breast Cancer Progression in the MCF10AT Xenograft Model

National Research Council Canada - National Science Library

Christman, Judith

2004-01-01

...) Collect microdissected tissue representative of each of the morphologically different stages of early breast cancer progression in the MCFlOAT model to obtain RNA and DNA for miroarray analysis...

Characterization of the expression of the pro-metastatic Mena(INV) isoform during breast tumor progression.

Science.gov (United States)

Oudin, Madeleine J; Hughes, Shannon K; Rohani, Nazanin; Moufarrej, Mira N; Jones, Joan G; Condeelis, John S; Lauffenburger, Douglas A; Gertler, Frank B

2016-03-01

Several functionally distinct isoforms of the actin regulatory Mena are produced by alternative splicing during tumor progression. Forced expression of the Mena(INV) isoform drives invasion, intravasation and metastasis. However, the abundance and distribution of endogenously expressed Mena(INV) within primary tumors during progression remain unknown, as most studies to date have only assessed relative mRNA levels from dissociated tumor samples. We have developed a Mena(INV) isoform-specific monoclonal antibody and used it to examine Mena(INV) expression patterns in mouse mammary and human breast tumors. Mena(INV) expression increases during tumor progression and to examine the relationship between Mena(INV) expression and markers for epithelial or mesenchymal status, stemness, stromal cell types and hypoxic regions. Further, while Mena(INV) robustly expressed in vascularized areas of the tumor, it is not confined to cells adjacent to blood vessels. Altogether, these data demonstrate the specificity and utility of the anti-Mena(INV)-isoform specific antibody, and provide the first description of endogenous Mena(INV) protein expression in mouse and human tumors.

[Breast tomosynthesis: a new tool for diagnosing breast cancer].

Science.gov (United States)

Martínez Miravete, P; Etxano, J

2015-01-01

Breast cancer continues to be the most common malignant tumor in women in occidental countries. Mammography is currently the technique of choice for screening programs; however, although it has been widely validated, mammography has its limitations, especially in dense breasts. Breast tomosynthesis is a revolutionary advance in the diagnosis of breast cancer. It makes it possible to define lesions that are occult in the glandular tissue and therefore to detect breast tumors that are impossible to see on conventional mammograms. In considering the combined use of mammography and tomosynthesis, many factors must be taken into account apart from cancer detection; these include additional radiation, the recall rate, and the time necessary to carry out and interpret the two tests. In this article, we review the technical principles of tomosynthesis, it main uses, and the future perspective for this imaging technique. Copyright © 2013 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Lattice-based model of ductal carcinoma in situ suggests rules for breast cancer progression to an invasive state.

Science.gov (United States)

Boghaert, Eline; Radisky, Derek C; Nelson, Celeste M

2014-12-01

Ductal carcinoma in situ (DCIS) is a heterogeneous group of non-invasive lesions of the breast that result from abnormal proliferation of mammary epithelial cells. Pathologists characterize DCIS by four tissue morphologies (micropapillary, cribriform, solid, and comedo), but the underlying mechanisms that distinguish the development and progression of these morphologies are not well understood. Here we explored the conditions leading to the emergence of the different morphologies of DCIS using a two-dimensional multi-cell lattice-based model that incorporates cell proliferation, apoptosis, necrosis, adhesion, and contractility. We found that the relative rates of cell proliferation and apoptosis governed which of the four morphologies emerged. High proliferation and low apoptosis favored the emergence of solid and comedo morphologies. In contrast, low proliferation and high apoptosis led to the micropapillary morphology, whereas high proliferation and high apoptosis led to the cribriform morphology. The natural progression between morphologies cannot be investigated in vivo since lesions are usually surgically removed upon detection; however, our model suggests probable transitions between these morphologies during breast cancer progression. Importantly, cribriform and comedo appear to be the ultimate morphologies of DCIS. Motivated by previous experimental studies demonstrating that tumor cells behave differently depending on where they are located within the mammary duct in vivo or in engineered tissues, we examined the effects of tissue geometry on the progression of DCIS. In agreement with our previous experimental work, we found that cells are more likely to invade from the end of ducts and that this preferential invasion is regulated by cell adhesion and contractility. This model provides additional insight into tumor cell behavior and allows the exploration of phenotypic transitions not easily monitored in vivo.

Nuclear structure theory. Annual technical progress report, October 1, 1976--September 30, 1977

International Nuclear Information System (INIS)

French, J.B.; Koltun, D.S.

1977-01-01

This report summarizes progress during the past year in the following areas of nuclear structure and reaction theory: (1) statistical spectroscopy, including giant resonances for beta and electromagnetic excitation and sum rules (including inverse-energy-weighted sum rules), statistical methods of truncating shell model spaces and renormalization of operators, study of state labelling and ''chains'' of groups, evaluation of fluctuation measures, technical aspects of operator averaging; (2) meson interactions with nuclei, including scattering and absorption of mesons by nuclei (general methods), models for absorption, single- and double-charge exchange of pions, role of rho mesons

FY 1992 work plan and technical progress reports

Energy Technology Data Exchange (ETDEWEB)

NONE

1992-11-01

The Desert Research Institute (DRI) is a division of the University of Nevada System devoted to multidisciplinary scientific research. For more than 25 years, DRI has conducted research for the US Department of Energy`s Nevada Field Office (DOE/NV) in support of operations at the Nevada Test Site (NTS). During that time, the research program has grown from an early focus on hydrologic studies to include the areas of geology, archaeology, environmental compliance and monitoring, statistics, database management, public education, and community relations. The range of DRI`s activities has also expanded to include a considerable amount of management and administrative support in addition to scientific investigations. DRI`s work plan for FY 1992 reflects a changing emphasis in DOE/NV activities from nuclear weapons testing to environmental restoration and monitoring. Most of the environmental projects from FY 1991 are continuing, and several new projects have been added to the Environmental Compliance Program. The Office of Technology Development Program, created during FY 1991, also includes a number of environmental projects. This document contains the FY 1992 work plan and quarterly technical progress reports for each DRI project.

Target volume definition for external beam partial breast radiotherapy: Clinical, pathological and technical studies informing current approaches

International Nuclear Information System (INIS)

Kirby, Anna M.; Coles, Charlotte E.; Yarnold, John R.

2010-01-01

Partial breast irradiation (PBI) is currently under investigation in several phase III trials and, following a recent consensus statement, its use off-study may increase despite ongoing uncertainty regarding optimal target volume definition. We review the clinical, pathological and technical evidence for target volume definition in external beam partial breast irradiation (EB-PBI). The optimal method of tumour bed (TB) delineation requires X-ray CT imaging of implanted excision cavity wall markers. The definition of clinical target volume (CTV) as TB plus concentric 15 mm margins is based on the anatomical distribution of multifocal and multicentric disease around the primary tumour in mastectomy specimens, and the clinical locations of local tumour relapse (LR) after breast conservation surgery. If the majority of LR originate from foci of residual invasive and/or intraduct disease in the vicinity of the TB after complete microscopic resection, CTV margin logically takes account of the position of primary tumour within the surgical resection specimen. The uncertain significance of independent primary tumours as sources of preventable LR, and of wound healing responses in stimulating LR, increases the difficulties in defining optimal CTV. These uncertainties may resolve after long-term follow-up of current PBI trials. By contrast, a commonly used 10 mm clinical to planning target volume (PTV) margin has a stronger evidence base, although departmental set-up errors need to be confirmed locally. A CTV-PTV margin >10 mm may be required in women with larger breasts and/or large seromas, whilst the role of image-guided radiotherapy with or without TB markers in reducing CTV-PTV margins needs to be explored.

Conventional surgery in breast cancer

International Nuclear Information System (INIS)

Tapia Herrera, Andres

2013-01-01

General aspects of breast cancer were described from the epidemiological point of view, clinical and pathological, as well as its impact at global and national levels. Parenchyma conservative surgery and/or breast skin was analyzed exhaustively as a cancer treatment analyzed exhaustively, to your specifications, requirements, technical aspects, risks, benefits, degree of oncological safety and benefits for patients [es

Progression-free survival as a potential surrogate for overall survival in metastatic breast cancer

Directory of Open Access Journals (Sweden)

Beauchemin C

2014-06-01

Full Text Available Catherine Beauchemin,1 Dan Cooper,2 Marie-Ève Lapierre,1 Louise Yelle,3 Jean Lachaine11Université de Montréal, Faculté de pharmacie, Montreal, 2Institut national d'excellence en santé et en services sociaux (INESSS, 3Centre Hospitalier de l'Université de Montréal – Hôpital Notre-Dame, Département de médecine, Université de Montréal, Montreal, QC, CanadaBackground: Progression-free survival (PFS and time to progression (TTP are frequently used to establish the clinical efficacy of anti-cancer drugs. However, the surrogacy of PFS/TTP for overall survival (OS remains a matter of uncertainty in metastatic breast cancer (mBC. This study assessed the relationship between PFS/TTP and OS in mBC using a trial-based approach.Methods: We conducted a systematic literature review according to the PICO method: 'Population' consisted of women with mBC; 'Interventions' and 'Comparators' were standard treatments for mBC or best supportive care; 'Outcomes' of interest were median PFS/TTP and OS. We first performed a correlation analysis between median PFS/TTP and OS, and then conducted subgroup analyses to explore possible reasons for heterogeneity. Then, we assessed the relationship between the treatment effect on PFS/TTP and OS. The treatment effect on PFS/TTP and OS was quantified by the absolute difference of median values. We also conducted linear regression analysis to predict the effects of a new anti-cancer drug on OS on the basis of its effects on PFS/TTP.Results: A total of 5,041 studies were identified, and 144 fulfilled the eligibility criteria. There was a statistically significant relationship between median PFS/TTP and OS across included trials (r=0.428; P<0.01. Correlation coefficient for the treatment effect on PFS/TTP and OS was estimated at 0.427 (P<0.01. The obtained linear regression equation was ΔOS =−0.088 (95% confidence interval [CI] −1.347–1.172 + 1.753 (95% CI 1.307–2.198 × ΔPFS (R2=0.86.Conclusion: Results of

Final Technical Progress Report: Development of Low-Cost Suspension Heliostat; December 7, 2011 - December 6, 2012

Energy Technology Data Exchange (ETDEWEB)

Bender, W.

2013-01-01

Final technical progress report of SunShot Incubator Solaflect Energy. The project succeeded in demonstrating that the Solaflect Suspension Heliostat design is viable for large-scale CSP installations. Canting accuracy is acceptable and is continually improving as Solaflect improves its understanding of this design. Cost reduction initiatives were successful, and there are still many opportunities for further development and further cost reduction.

Progression criteria for cancer antigen 15.3 and carcinoembryonic antigen in metastatic breast cancer compared by computer simulation of marker data

DEFF Research Database (Denmark)

Sölétormos, G; Hyltoft Petersen, P; Dombernowsky, P

2000-01-01

.3 and carcinoembryonic antigen concentrations were combined with representative values for background variations in a computer simulation model. Fifteen criteria for assessment of longitudinal tumor marker data were obtained from the literature and computerized. Altogether, 7200 different patients, each based on 50......BACKGROUND: We investigated the utility of computer simulation models for performance comparisons of different tumor marker assessment criteria to define progression or nonprogression of metastatic breast cancer. METHODS: Clinically relevant values for progressive cancer antigen 15...... of progression. CONCLUSIONS: The computer simulation model is a fast, effective, and inexpensive approach for comparing the diagnostic potential of assessment criteria during clinically relevant conditions of steady-state and progressive disease. The model systems can be used to generate tumor marker assessment...

Breast lymphoma

African Journals Online (AJOL)

To fulfil the criteria for primary breast lymphoma, the following characteristics were reqUired: (I) technically adequate specimens; (iI) mammary tissue and lymphomatous infiltrate in close association; (iil) no evidence of concurrent widespread disease; and (iv) no previous. Haematology/Oncology Division, Department of ...

Lattice-based model of ductal carcinoma in situ suggests rules for breast cancer progression to an invasive state.

Directory of Open Access Journals (Sweden)

Eline Boghaert

2014-12-01

Full Text Available Ductal carcinoma in situ (DCIS is a heterogeneous group of non-invasive lesions of the breast that result from abnormal proliferation of mammary epithelial cells. Pathologists characterize DCIS by four tissue morphologies (micropapillary, cribriform, solid, and comedo, but the underlying mechanisms that distinguish the development and progression of these morphologies are not well understood. Here we explored the conditions leading to the emergence of the different morphologies of DCIS using a two-dimensional multi-cell lattice-based model that incorporates cell proliferation, apoptosis, necrosis, adhesion, and contractility. We found that the relative rates of cell proliferation and apoptosis governed which of the four morphologies emerged. High proliferation and low apoptosis favored the emergence of solid and comedo morphologies. In contrast, low proliferation and high apoptosis led to the micropapillary morphology, whereas high proliferation and high apoptosis led to the cribriform morphology. The natural progression between morphologies cannot be investigated in vivo since lesions are usually surgically removed upon detection; however, our model suggests probable transitions between these morphologies during breast cancer progression. Importantly, cribriform and comedo appear to be the ultimate morphologies of DCIS. Motivated by previous experimental studies demonstrating that tumor cells behave differently depending on where they are located within the mammary duct in vivo or in engineered tissues, we examined the effects of tissue geometry on the progression of DCIS. In agreement with our previous experimental work, we found that cells are more likely to invade from the end of ducts and that this preferential invasion is regulated by cell adhesion and contractility. This model provides additional insight into tumor cell behavior and allows the exploration of phenotypic transitions not easily monitored in vivo.

HER family kinase domain mutations promote tumor progression and can predict response to treatment in human breast cancer

KAUST Repository

Boulbes, Delphine R.; Arold, Stefan T.; Chauhan, Gaurav B.; Blachno, Korina V.; Deng, Nanfu; Chang, Wei-Chao; Jin, Quanri; Huang, Tzu-Hsuan; Hsu, Jung-Mao; Brady, Samuel W.; Bartholomeusz, Chandra; Ladbury, John E.; Stone, Steve; Yu, Dihua; Hung, Mien-Chie; Esteva, Francisco J.

2014-01-01

Resistance to HER2-targeted therapies remains a major obstacle in the treatment of HER2-overexpressing breast cancer. Understanding the molecular pathways that contribute to the development of drug resistance is needed to improve the clinical utility of novel agents, and to predict the success of targeted personalized therapy based on tumor-specific mutations. Little is known about the clinical significance of HER family mutations in breast cancer. Because mutations within HER1/EGFR are predictive of response to tyrosine kinase inhibitors (TKI) in lung cancer, we investigated whether mutations in HER family kinase domains are predictive of response to targeted therapy in HER2-overexpressing breast cancer. We sequenced the HER family kinase domains from 76 HER2-overexpressing invasive carcinomas and identified 12 missense variants. Patients whose tumors carried any of these mutations did not respond to HER2 directed therapy in the metastatic setting. We developed mutant cell lines and used structural analyses to determine whether changes in protein conformation could explain the lack of response to therapy. We also functionally studied all HER2 mutants and showed that they conferred an aggressive phenotype and altered effects of the TKI lapatinib. Our data demonstrate that mutations in the finely tuned HER kinase domains play a critical function in breast cancer progression and may serve as prognostic and predictive markers.

HER family kinase domain mutations promote tumor progression and can predict response to treatment in human breast cancer

KAUST Repository

Boulbes, Delphine R.

2014-11-11

Resistance to HER2-targeted therapies remains a major obstacle in the treatment of HER2-overexpressing breast cancer. Understanding the molecular pathways that contribute to the development of drug resistance is needed to improve the clinical utility of novel agents, and to predict the success of targeted personalized therapy based on tumor-specific mutations. Little is known about the clinical significance of HER family mutations in breast cancer. Because mutations within HER1/EGFR are predictive of response to tyrosine kinase inhibitors (TKI) in lung cancer, we investigated whether mutations in HER family kinase domains are predictive of response to targeted therapy in HER2-overexpressing breast cancer. We sequenced the HER family kinase domains from 76 HER2-overexpressing invasive carcinomas and identified 12 missense variants. Patients whose tumors carried any of these mutations did not respond to HER2 directed therapy in the metastatic setting. We developed mutant cell lines and used structural analyses to determine whether changes in protein conformation could explain the lack of response to therapy. We also functionally studied all HER2 mutants and showed that they conferred an aggressive phenotype and altered effects of the TKI lapatinib. Our data demonstrate that mutations in the finely tuned HER kinase domains play a critical function in breast cancer progression and may serve as prognostic and predictive markers.

Generation and focusing of pulsed intense ion beams. Technical progress report, 20 August 1981-30 September 1982

International Nuclear Information System (INIS)

Hammer, D.A.; Kusse, B.R.; Sudan, R.N.

1983-07-01

The progress on this contract is described in two parts. The first deals with the technical operation of the LION accelerator which is the exact equivalent to one line of PBFA-I. The second part is concerned with the experimental results on the ion diode mounted at the front end of the LION accelerator

Breast

International Nuclear Information System (INIS)

Ribeiro, G.G.

1985-01-01

The treatment of malignant disease of the breast arouses more controversy and emotion than that of any other form of malignant disease. Many clinical trials have been carried out and others are still in progress. In addition, research work continues in regard to other aspects of the disease, such as epidemiology, population screening, and endocrine factors; yet little is really known about the true biological nature of carcinoma of the breast. A vast amount of literature has accumulated on the treatment of ''operable'' carcinoma of the breast, but it is not proposed to discuss here the merits or demerits of the various suggested treatments. Instead this chapter will be confined to the practical management of carcinoma of the breast as seen from the point of view of radiotherapist. For this reason greater attention will be paid to the radiotherapy techniques as practised at the Christie Hospital

The Regulation of the Angiogenic Factor FGF Binding Protein (FGF-BP) by the APC/Beta-Catenin Signaling Pathway in the Progression of Breast Cancer

National Research Council Canada - National Science Library

Stylianou, Dora

2004-01-01

...) to study the expression of FGF-BP in mammary tumorigenesis progression of the APC/+ mouse and 2) to determine the mechanism of regulation of FGF-BP b the APC/beta-catenin signaling pathway in breast cancer...

The Regulation of the Angiogenic Factor FGF Binding Protein (FGF-BP) by the APC/Beta-Catenin Signaling Pathway in the Progression of Breast Cancer

National Research Council Canada - National Science Library

Stylianou, Dora

2003-01-01

...) to study the expression of FGF-BP in mammary tumorigenesis% progression of the APC/+ mouse and 2) to determine the mechanism of regulation of FGF-BP by the APC/beta- catenin signaling pathway in breast cancer...

IGF-IR Signaling in Breast Cancer

National Research Council Canada - National Science Library

Surmacz, Ewa

1997-01-01

Experimental and clinical evidence suggests that the insulin-like growth factor (IGF) system is involved in the growth of breast cancer cells in vitro and may be important in breast cancer etiology and progression...

Primary lymphoma of the breast involving both axillae with bilateral breast carcinoma

Directory of Open Access Journals (Sweden)

Rubin Gary

2008-05-01

Full Text Available Abstract Background Primary Non-Hodgkin's Lymphoma (PHNL of the breast is a rare entity, while secondary involvement of the breast with diffuse disease of Non-Hodgkin's lymphoma (NHL is more common. However, PNHL is the most frequent haematopoietic tumour of the breast. Diagnostic criteria for PNHL of the breast are presence of technically adequate pathologic specimens, close association of mammary tissue and lymphomatous infiltrate, no prior diagnosis of an extarammamary lymphoma, and no evidence of concurrent widespread disease, except for ipsilateral axillary lymph nodes if concomitant with the primary lesion. Case presentation A 57-year-old woman was recalled because her screening mammograms revealed three separate lesions in her right breast and one in the left. Histology of the lesions confirmed lymphoma in one breast with ductal carcinoma in the other. Conclusion Most of reported cases in literature have been involving the right breast, and almost all the patients were females. NHLs of the breast typically present as unilateral mass; the frequency of bilateral disease at first presentation ranges from 5–25%. Our objective is to report a case of primary lymphoma of the breast involving both axillae with concomitant bilateral primary breast cancer which has not been reported yet to our best of knowledge in literature.

The U.S. nuclear waste management program - technical progress at Yucca Mountain

Energy Technology Data Exchange (ETDEWEB)

Barrett, L.H. [U.S. Department of Energy (United States)

2001-07-01

This paper discusses the current status of a national program being developed by the U.S. Department of Energy for the management of spent nuclear fuel and high-level radioactive waste produced by civilian nuclear power generation and defense-related activities. In 1987 the U.S. Congress directed the Department to characterize the Yucca Mountain site in Nevada and determine its suitability for development of a geologic repository. This paper will focus on the technical progress that has been made after more than 15 years of scientific and engineering investigations at Yucca Mountain, and the remaining work that is being done to support a decision on whether to recommend the site for development of a geologic repository. (author)

Mammography and breast sonography in transsexual women

International Nuclear Information System (INIS)

Weyers, S.; Villeirs, G.; Vanherreweghe, E.; Verstraelen, H.; Monstrey, S.; Van den Broecke, R.; Gerris, J.

2010-01-01

Data on the necessity of performing screening mammographies in transsexual women are lacking. The main objective of this study was to assess the possibility to perform mammography and breast sonography in transsexual women. Fifty Dutch-speaking transsexual women were interviewed about the following: attitude towards mammography and breast sonography, importance attributed to and satisfaction with breast appearance, opinion about the necessity of breast check-up, expectations regarding discomfort during the exams and knowledge about the breast surgery. A fasting blood sample, clinical breast exam, mammography and breast sonography were performed. At mammography the following parameters were noted: density, technical quality, location of the prostheses, presence of any abnormalities and painfulness. At sonography the following parameters were recorded: density, presence of cysts, visualisation of retro-areolar ducts or any abnormalities. Twenty-three percent of patients are not aware of the type of breast implants and 79% do not know their position to the pectoral muscles. Patient satisfaction with the appearance of their breasts was rather high (7.94 on a scale of 0-10). Mean expected and experienced pain from mammography was low (4.37 and 2.00 respectively). There was no statistically significant difference in expected pain between those who already had mammography and those who did not. There was a significant positive correlation between the expected and the experienced pain. Mammography and breast sonography were technically feasible and no gross anomalies were detected. Since both exams were judged as nearly painless, 98% of transsexual women intended to come back if they would be invited. Since breast cancer risk in transsexual women is largely unknown and breast exams are very well accepted, breast screening habits in this population should not differ from those of biological women.

Mammography and breast sonography in transsexual women

Energy Technology Data Exchange (ETDEWEB)

Weyers, S., E-mail: steven.weyers@ugent.b [Department of Gynecology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent (Belgium); Villeirs, G.; Vanherreweghe, E. [Department of Radiology, Ghent University Hospital, Ghent (Belgium); Verstraelen, H. [Department of Gynecology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent (Belgium); Monstrey, S. [Department of Plastic Surgery, Ghent University Hospital, Ghent (Belgium); Van den Broecke, R.; Gerris, J. [Department of Gynecology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent (Belgium)

2010-06-15

Data on the necessity of performing screening mammographies in transsexual women are lacking. The main objective of this study was to assess the possibility to perform mammography and breast sonography in transsexual women. Fifty Dutch-speaking transsexual women were interviewed about the following: attitude towards mammography and breast sonography, importance attributed to and satisfaction with breast appearance, opinion about the necessity of breast check-up, expectations regarding discomfort during the exams and knowledge about the breast surgery. A fasting blood sample, clinical breast exam, mammography and breast sonography were performed. At mammography the following parameters were noted: density, technical quality, location of the prostheses, presence of any abnormalities and painfulness. At sonography the following parameters were recorded: density, presence of cysts, visualisation of retro-areolar ducts or any abnormalities. Twenty-three percent of patients are not aware of the type of breast implants and 79% do not know their position to the pectoral muscles. Patient satisfaction with the appearance of their breasts was rather high (7.94 on a scale of 0-10). Mean expected and experienced pain from mammography was low (4.37 and 2.00 respectively). There was no statistically significant difference in expected pain between those who already had mammography and those who did not. There was a significant positive correlation between the expected and the experienced pain. Mammography and breast sonography were technically feasible and no gross anomalies were detected. Since both exams were judged as nearly painless, 98% of transsexual women intended to come back if they would be invited. Since breast cancer risk in transsexual women is largely unknown and breast exams are very well accepted, breast screening habits in this population should not differ from those of biological women.

Quality indicators for breast cancer

DEFF Research Database (Denmark)

Poortmans, Philip; Aznar, Marianne; Bartelink, Harry

2012-01-01

Radiation therapy for breast cancer has considerably changed over the years, from simple simulator-based 2-dimensional techniques to sophisticated image-guided individualized treatments, with maximally protected normal structures. This has led to a substantial improvement in the outcome of breast...... cancer patients in terms of disease control, survival, and quality of life. This progress is based on clinical research and paralleled by progress in delivering sophisticated radiation treatment. Clinical trials resulted in identifying patients groups who will benefit from radiation treatment. They also...

Structure, Function, and Applications of the Georgetown-Einstein (GE) Breast Cancer Simulation Model.

Science.gov (United States)

Schechter, Clyde B; Near, Aimee M; Jayasekera, Jinani; Chandler, Young; Mandelblatt, Jeanne S

2018-04-01

The Georgetown University-Albert Einstein College of Medicine breast cancer simulation model (Model GE) has evolved over time in structure and function to reflect advances in knowledge about breast cancer, improvements in early detection and treatment technology, and progress in computing resources. This article describes the model and provides examples of model applications. The model is a discrete events microsimulation of single-life histories of women from multiple birth cohorts. Events are simulated in the absence of screening and treatment, and interventions are then applied to assess their impact on population breast cancer trends. The model accommodates differences in natural history associated with estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) biomarkers, as well as conventional breast cancer risk factors. The approach for simulating breast cancer natural history is phenomenological, relying on dates, stage, and age of clinical and screen detection for a tumor molecular subtype without explicitly modeling tumor growth. The inputs to the model are regularly updated to reflect current practice. Numerous technical modifications, including the use of object-oriented programming (C++), and more efficient algorithms, along with hardware advances, have increased program efficiency permitting simulations of large samples. The model results consistently match key temporal trends in US breast cancer incidence and mortality. The model has been used in collaboration with other CISNET models to assess cancer control policies and will be applied to evaluate clinical trial design, recurrence risk, and polygenic risk-based screening.

Pathogenesis and progression of fibroepithelial breast tumors

NARCIS (Netherlands)

Kuijper, Arno

2006-01-01

Fibroadenoma and phyllodes tumor are fibroepithelial breast tumors. These tumors are biphasic, i.e. they are composed of stroma and epithelium. The behavior of fibroadenomas is benign, whereas phyllodes tumors can recur and even metastasize. Classification criteria for both tumors show considerable

Dietary and other risk factors in women having fibrocystic breast conditions with and without concurrent breast cancer: a nested case-control study in Shanghai, China.

Science.gov (United States)

Li, Wenjin; Ray, Roberta M; Lampe, Johanna W; Lin, Ming-Gang; Gao, Dao Li; Wu, Chunyuan; Nelson, Zakia C; Fitzgibbons, E Dawn; Horner, Neilann; Hu, Yong Wei; Shannon, Jackilen; Satia, Jessie A; Patterson, Ruth E; Stalsberg, Helge; Thomas, David B

2005-07-20

Risk of breast cancer is increased in women with proliferative benign breast conditions. Most of these conditions, however, do not progress to breast cancer. The purpose of our study was to identify factors possibly associated with this progression. Women with proliferative fibrocystic breast conditions alone (214), and women with proliferative fibrocystic breast conditions and concurrent breast cancer (130), were compared to each other, and each of these groups of women were also compared to 1,070 controls; and 176 women with non-proliferative benign breast conditions alone, and 155 also with breast cancer, were similarly compared. All study subjects were selected from a cohort of women enrolled in a trial of breast self-examination in Shanghai. Women were interviewed to ascertain information on suspected risk factors for breast cancer and dietary habits. Conditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Increased risks of both proliferative fibrocystic breast conditions alone, and with breast cancer, were associated with low parity, a prior benign breast lump and breast cancer in a first-degree relative. Decreasing trends in the risk of both conditions with increasing intake of fruits and vegetables were observed. No factors were significantly associated with risk of breast cancer relative to risk of proliferative changes. Similar, but in some instances weaker, associations were observed for non-proliferative fibrocystic conditions with and without breast cancer. The possible risk or protective factors that were observed in our study most likely alter the risk of breast cancer at an early stage in the carcinogenic process, and probably do not alter risk of progression from proliferative fibrocystic breast conditions to breast cancer. Copyright 2005 Wiley-Liss, Inc.

A Case Report of Breast Sparganosis in a Patient with Ipsilateral Breast Cancer: MRI and Ultrasonographic Findings

Energy Technology Data Exchange (ETDEWEB)

Lee, Yoo Jin; Bae, Young Tae; Kim, Jee Yeon [Pusan National University Hospital, Pusan National University School of Medicine, Busan (Korea, Republic of); Choo, Ki Seok [Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan (Korea, Republic of)

2010-12-15

Sparganosis of the breast is a quite rare parasitic infection of humans and presents as soft tissue masses that mimic breast malignancy or benign tumor, such as fibroadenoma. We present here a case of histologically confirmed breast sparganosis in the upper inner quadrant of the right breast with coexisting breast cancer in the ipsilateral breast upper outer quadrant. Ultrasonography of breast sparganosis showed a well defined, tubular hypoechoic mass with discrete multilayered wall and tubule-in tubule appearance, surrounded by heterogenous hyperechoic areas in the subcutaneous fat layer of the breast. MRI revealed an elongated tubular structure with persistent and progressive enhancement. This is the second report concerned with the MRI and ultrasonographic findings of breast sparganosis and the first report of breast sparganosis in a patient with ipsilateral breast cancer

The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Kindergarten. Technical Report # 0921

Science.gov (United States)

Alonzo, Julie; Tindal, Gerald

2009-01-01

In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in kindergarten. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2008 and administered to approximately 2800 students from…

A high protein moderate carbohydrate diet fed at discrete meals reduces early progression of N-methyl-N-nitrosourea-induced breast tumorigenesis in rats

Directory of Open Access Journals (Sweden)

Singletary Keith W

2010-01-01

Full Text Available Abstract Breast cancer is the most prevalent cancer in American women. Dietary factors are thought to have a strong influence on breast cancer incidence. This study utilized a meal-feeding protocol with female Sprague-Dawley rats to evaluate effects of two ratios of carbohydrate:protein on promotion and early progression of breast tissue carcinomas. Mammary tumors were induced by N-methyl-N-nitrosourea (MNU at 52 d of age. Post-induction, animals were assigned to consume either a low protein high carbohydrate diet (LPHC; 15% and 60% of energy, respectively or a high protein moderate carbohydrate diet (HPMC; 35% and 40% of energy, respectively for 10 wk. Animals were fed 3 meals/day to mimic human absorption and metabolism patterns. The rate of palpable tumor incidence was reduced in HPMC relative to LPHC (12.9 ± 1.4%/wk vs. 18.2 ± 1.3%/wk. At 3 wk, post-prandial serum insulin was larger in the LPHC relative to HPMC (+136.4 ± 33.1 pmol/L vs. +38.1 ± 23.4 pmol/L, while at 10 wk there was a trend for post-prandial IGF-I to be increased in HPMC (P = 0.055. There were no differences in tumor latency, tumor surface area, or cumulative tumor mass between diet groups. The present study provides evidence that reducing the dietary carbohydrate:protein ratio attenuates the development of mammary tumors. These findings are consistent with reduced post-prandial insulin release potentially diminishing the proliferative environment required for breast cancer tumors to progress.

Decontamination Systems Information and Research Program. Quarterly technical progress report, January 1--March 31, 1993

Energy Technology Data Exchange (ETDEWEB)

1993-04-01

This reports reports the progress/efforts performed on six technical projects: 1. systematic assessment of the state of hazardous waste clean-up technologies; 2. site remediation technologies (SRT):drain- enhanced soil flushing for organic contaminants removal; 3. SRT: in situ bio-remediation of organic contaminants; 4. excavation systems for hazardous waste sites: dust control methods for in-situ nuclear waste handling; 5. chemical destruction of polychlorinated biphenyls; and 6. development of organic sensors: monolayer and multilayer self-assembled films for chemical sensors.

Current status of gene therapy for breast cancer: progress and challenges

Directory of Open Access Journals (Sweden)

McCrudden CM

2014-11-01

Full Text Available Cian M McCrudden, Helen O McCarthySchool of Pharmacy, Queen’s University Belfast, Belfast, UKAbstract: Breast cancer is characterized by a series of genetic mutations and is therefore ideally placed for gene therapy intervention. The aim of gene therapy is to deliver a nucleic acid-based drug to either correct or destroy the cells harboring the genetic aberration. More recently, cancer gene therapy has evolved to also encompass delivery of RNA interference technologies, as well as cancer DNA vaccines. However, the bottleneck in creating such nucleic acid pharmaceuticals lies in the delivery. Deliverability of DNA is limited as it is prone to circulating nucleases; therefore, numerous strategies have been employed to aid with biological transport. This review will discuss some of the viral and nonviral approaches to breast cancer gene therapy, and present the findings of clinical trials of these therapies in breast cancer patients. Also detailed are some of the most recent developments in nonviral approaches to targeting in breast cancer gene therapy, including transcriptional control, and the development of recombinant, multifunctional bio-inspired systems. Lastly, DNA vaccines for breast cancer are documented, with comment on requirements for successful pharmaceutical product development.Keywords: breast cancer, gene therapy, nonviral, clinical trial

Breast cancer statistics, 2011.

Science.gov (United States)

DeSantis, Carol; Siegel, Rebecca; Bandi, Priti; Jemal, Ahmedin

2011-01-01

In this article, the American Cancer Society provides an overview of female breast cancer statistics in the United States, including trends in incidence, mortality, survival, and screening. Approximately 230,480 new cases of invasive breast cancer and 39,520 breast cancer deaths are expected to occur among US women in 2011. Breast cancer incidence rates were stable among all racial/ethnic groups from 2004 to 2008. Breast cancer death rates have been declining since the early 1990s for all women except American Indians/Alaska Natives, among whom rates have remained stable. Disparities in breast cancer death rates are evident by state, socioeconomic status, and race/ethnicity. While significant declines in mortality rates were observed for 36 states and the District of Columbia over the past 10 years, rates for 14 states remained level. Analyses by county-level poverty rates showed that the decrease in mortality rates began later and was slower among women residing in poor areas. As a result, the highest breast cancer death rates shifted from the affluent areas to the poor areas in the early 1990s. Screening rates continue to be lower in poor women compared with non-poor women, despite much progress in increasing mammography utilization. In 2008, 51.4% of poor women had undergone a screening mammogram in the past 2 years compared with 72.8% of non-poor women. Encouraging patients aged 40 years and older to have annual mammography and a clinical breast examination is the single most important step that clinicians can take to reduce suffering and death from breast cancer. Clinicians should also ensure that patients at high risk of breast cancer are identified and offered appropriate screening and follow-up. Continued progress in the control of breast cancer will require sustained and increased efforts to provide high-quality screening, diagnosis, and treatment to all segments of the population. Copyright © 2011 American Cancer Society, Inc.

Intensity modulated radiotherapy for breast cancer

International Nuclear Information System (INIS)

Riou, O.; Fenoglietto, P.; Lemanski, C.; Azria, D.

2012-01-01

Intensity modulated radiotherapy (IMRT) is a technique allowing dose escalation and normal tissue sparing for various cancer types. For breast cancer, the main goals when using IMRT were to improve dose homogeneity within the breast and to enhance coverage of complex target volumes. Nonetheless, better heart and lung protections are achievable with IMRT as compared to standard irradiation for difficult cases. Three prospective randomized controlled trials of IMRT versus standard treatment showed that a better breast homogeneity can translate into better overall cosmetic results. Dosimetric and clinical studies seem to indicate a benefit of IMRT for lymph nodes irradiation, bilateral treatment, left breast and chest wall radiotherapy, or accelerated partial breast irradiation. The multiple technical IMRT solutions available tend to indicate a widespread use for breast irradiation. Nevertheless, indications for breast IMRT should be personalized and selected according to the expected benefit for each individual. (authors)

GPHS-RTGs in support of the Cassini Mission. Semi annual technical progress report, 1 April 1996--29 September 1996

International Nuclear Information System (INIS)

1996-01-01

This technical progress report discusses work on the Radioisotope Generators and Ancillary Activities for the Cassini spacecraft. The Cassini spacecraft is expected to launch in October 1997, and will explore Saturn and its moons. This progress report discusses issues in: spacecraft integration and liason, engineering support, safety, qualified unicouple fabrication, ETG fabrication and testing, ground support equipment, RTG shipping and launch support, designs, reviews and mission application. Safety analysis of the RTGs during reentry and launch accidents are covered. This report covers the period of April 1 to September 29, 1996

Technical reliability of geological disposal for high-level radioactive wastes in Japan. The second progress report. Part 1. Geological environment of Japan

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-11-01

Based on the Advisory Committee Report on Nuclear Fuel Cycle Backend Policy submitted to the Japanese Government in 1997, JNC documents the progress of research and development program in the form of the second progress report (the first one published in 1992). It summarizes an evaluation of the technical reliability and safety of the geological disposal concept for high-level radioactive wastes (HLW) in Japan. The present document, the part 1 of the progress report, describes first in detail the role of geological environment in high-level radioactive wastes disposal, the features of Japanese geological environment, and programs to proceed the investigation in geological environment. The following chapter summarizes scientific basis for possible existence of stable geological environment, stable for a long period needed for the HLW disposal in Japan including such natural phenomena as volcano and faults. The results of the investigation of the characteristics of bed-rocks and groundwater are presented. These are important for multiple barrier system construction of deep geological disposal. The report furthermore describes the present status of technical and methodological progress in investigating geological environment and finally on the results of natural analog study in Tono uranium deposits area. (Ohno, S.)

Genome-wide association study of susceptibility loci for breast cancer in Sardinian population.

Science.gov (United States)

Palomba, Grazia; Loi, Angela; Porcu, Eleonora; Cossu, Antonio; Zara, Ilenia; Budroni, Mario; Dei, Mariano; Lai, Sandra; Mulas, Antonella; Olmeo, Nina; Ionta, Maria Teresa; Atzori, Francesco; Cuccuru, Gianmauro; Pitzalis, Maristella; Zoledziewska, Magdalena; Olla, Nazario; Lovicu, Mario; Pisano, Marina; Abecasis, Gonçalo R; Uda, Manuela; Tanda, Francesco; Michailidou, Kyriaki; Easton, Douglas F; Chanock, Stephen J; Hoover, Robert N; Hunter, David J; Schlessinger, David; Sanna, Serena; Crisponi, Laura; Palmieri, Giuseppe

2015-05-10

Despite progress in identifying genes associated with breast cancer, many more risk loci exist. Genome-wide association analyses in genetically-homogeneous populations, such as that of Sardinia (Italy), could represent an additional approach to detect low penetrance alleles. We performed a genome-wide association study comparing 1431 Sardinian patients with non-familial, BRCA1/2-mutation-negative breast cancer to 2171 healthy Sardinian blood donors. DNA was genotyped using GeneChip Human Mapping 500 K Arrays or Genome-Wide Human SNP Arrays 6.0. To increase genomic coverage, genotypes of additional SNPs were imputed using data from HapMap Phase II. After quality control filtering of genotype data, 1367 cases (9 men) and 1658 controls (1156 men) were analyzed on a total of 2,067,645 SNPs. Overall, 33 genomic regions (67 candidate SNPs) were associated with breast cancer risk at the p <  0(-6) level. Twenty of these regions contained defined genes, including one already associated with breast cancer risk: TOX3. With a lower threshold for preliminary significance to p < 10(-5), we identified 11 additional SNPs in FGFR2, a well-established breast cancer-associated gene. Ten candidate SNPs were selected, excluding those already associated with breast cancer, for technical validation as well as replication in 1668 samples from the same population. Only SNP rs345299, located in intron 1 of VAV3, remained suggestively associated (p-value, 1.16 x 10(-5)), but it did not associate with breast cancer risk in pooled data from two large, mixed-population cohorts. This study indicated the role of TOX3 and FGFR2 as breast cancer susceptibility genes in BRCA1/2-wild-type breast cancer patients from Sardinian population.

Genome-wide association study of susceptibility loci for breast cancer in Sardinian population

International Nuclear Information System (INIS)

Palomba, Grazia; Loi, Angela; Porcu, Eleonora; Cossu, Antonio; Zara, Ilenia

2015-01-01

Despite progress in identifying genes associated with breast cancer, many more risk loci exist. Genome-wide association analyses in genetically-homogeneous populations, such as that of Sardinia (Italy), could represent an additional approach to detect low penetrance alleles. We performed a genome-wide association study comparing 1431 Sardinian patients with non-familial, BRCA1/2-mutation-negative breast cancer to 2171 healthy Sardinian blood donors. DNA was genotyped using GeneChip Human Mapping 500 K Arrays or Genome-Wide Human SNP Arrays 6.0. To increase genomic coverage, genotypes of additional SNPs were imputed using data from HapMap Phase II. After quality control filtering of genotype data, 1367 cases (9 men) and 1658 controls (1156 men) were analyzed on a total of 2,067,645 SNPs. Overall, 33 genomic regions (67 candidate SNPs) were associated with breast cancer risk at the p < 10 −6 level. Twenty of these regions contained defined genes, including one already associated with breast cancer risk: TOX3. With a lower threshold for preliminary significance to p < 10 −5 , we identified 11 additional SNPs in FGFR2, a well-established breast cancer-associated gene. Ten candidate SNPs were selected, excluding those already associated with breast cancer, for technical validation as well as replication in 1668 samples from the same population. Only SNP rs345299, located in intron 1 of VAV3, remained suggestively associated (p-value, 1.16x10 −5 ), but it did not associate with breast cancer risk in pooled data from two large, mixed-population cohorts. This study indicated the role of TOX3 and FGFR2 as breast cancer susceptibility genes in BRCA1/2-wild-type breast cancer patients from Sardinian population. The online version of this article (doi:10.1186/s12885-015-1392-9) contains supplementary material, which is available to authorized users

Index to Nuclear Safety: a technical progress review by chronology, permuted title, and author. Vol. 11(1)--Vol. 18(6)

Energy Technology Data Exchange (ETDEWEB)

Cottrell, W.B.; Klein, A.

1978-04-11

This index to Nuclear Safety covers articles published in Nuclear Safety, Vol. 11, No. 1 (January-February 1970), through Vol. 18, No. 6 (November-December 1977). It is divided into three sections: a chronological list of articles (including abstracts) followed by a permuted-title (KWIC) index and an author index. Nuclear Safety, a bimonthly technical progress review prepared by the Nuclear Safety Information Center (NSIC), covers all safety aspects of nuclear power reactors and associated facilities. Over 450 technical articles published in Nuclear Safety in the last eight years are listed in this index.

Index to Nuclear Safety: a technical progress review by chronology, permuted title, and author. Vol. 11(1)--Vol. 18(6)

International Nuclear Information System (INIS)

Cottrell, W.B.; Klein, A.

1978-01-01

This index to Nuclear Safety covers articles published in Nuclear Safety, Vol. 11, No. 1 (January-February 1970), through Vol. 18, No. 6 (November-December 1977). It is divided into three sections: a chronological list of articles (including abstracts) followed by a permuted-title (KWIC) index and an author index. Nuclear Safety, a bimonthly technical progress review prepared by the Nuclear Safety Information Center (NSIC), covers all safety aspects of nuclear power reactors and associated facilities. Over 450 technical articles published in Nuclear Safety in the last eight years are listed in this index

Propranolol and survival from breast cancer

DEFF Research Database (Denmark)

Cardwell, Chris R; Pottegård, Anton; Vaes, Evelien

2016-01-01

BACKGROUND: Preclinical studies have demonstrated that propranolol inhibits several pathways involved in breast cancer progression and metastasis. We investigated whether breast cancer patients who used propranolol, or other non-selective beta-blockers, had reduced breast cancer-specific or all......-cause mortality in eight European cohorts. METHODS: Incident breast cancer patients were identified from eight cancer registries and compiled through the European Cancer Pharmacoepidemiology Network. Propranolol and non-selective beta-blocker use was ascertained for each patient. Breast cancer-specific and all......-analysis techniques. Dose-response analyses by number of prescriptions were also performed. Analyses were repeated investigating propranolol use before cancer diagnosis. RESULTS: The combined study population included 55,252 and 133,251 breast cancer patients in the analysis of breast cancer-specific and all...

Lysine methyltransferase SMYD2 promotes triple negative breast cancer progression.

Science.gov (United States)

Li, Linda Xiaoyan; Zhou, Julie Xia; Calvet, James P; Godwin, Andrew K; Jensen, Roy A; Li, Xiaogang

2018-02-27

We identified SMYD2, a SMYD (SET and MYND domain) family protein with lysine methyltransferase activity, as a novel breast cancer oncogene. SMYD2 was expressed at significantly higher levels in breast cancer cell lines and in breast tumor tissues. Silencing of SMYD2 by RNAi in triple-negative breast cancer (TNBC) cell lines or inhibition of SMYD2 with its specific inhibitor, AZ505, significantly reduced tumor growth in vivo. SMYD2 executes this activity via methylation and activation of its novel non-histone substrates, including STAT3 and the p65 subunit of NF-κB, leading to increased TNBC cell proliferation and survival. There are cross-talk and synergistic effects among SMYD2, STAT3, and NF-κB in TNBC cells, in that STAT3 can contribute to the modification of NF-κB p65 subunit post-translationally by recruitment of SMYD2, whereas the p65 subunit of NF-κB can also contribute to the modification of STAT3 post-translationally by recruitment of SMYD2, leading to methylation and activation of STAT3 and p65 in these cells. The expression of SMYD2 can be upregulated by IL-6-STAT3 and TNFα-NF-κB signaling, which integrates epigenetic regulation to inflammation in TNBC development. In addition, we have identified a novel SMYD2 transcriptional target gene, PTPN13, which links SMYD2 to other known breast cancer associated signaling pathways, including ERK, mTOR, and Akt signaling via PTPN13 mediated phosphorylation.

Alterations in Vitamin D signalling and metabolic pathways in breast cancer progression: a study of VDR, CYP27B1 and CYP24A1 expression in benign and malignant breast lesions Vitamin D pathways unbalanced in breast lesions

International Nuclear Information System (INIS)

Lopes, Nair; Schmitt, Fernando; Sousa, Bárbara; Martins, Diana; Gomes, Madalena; Vieira, Daniella; Veronese, Luiz A; Milanezi, Fernanda; Paredes, Joana; Costa, José L

2010-01-01

Breast cancer is a heterogeneous disease associated with different patient prognosis and responses to therapy. Vitamin D has been emerging as a potential treatment for cancer, as it has been demonstrated that it modulates proliferation, apoptosis, invasion and metastasis, among others. It acts mostly through the Vitamin D receptor (VDR) and the synthesis and degradation of this hormone are regulated by the enzymes CYP27B1 and CYP24A1, respectively. We aimed to study the expression of these three proteins by immunohistochemistry in a series of breast lesions. We have used a cohort comprising normal breast, benign mammary lesions, carcinomas in situ and invasive carcinomas and assessed the expression of the VDR, CYP27B1 and CYP24A1 by immunohistochemistry. The results that we have obtained show that all proteins are expressed in the various breast tissues, although at different amounts. The VDR was frequently expressed in benign lesions (93.5%) and its levels of expression were diminished in invasive tumours (56.2%). Additionally, the VDR was strongly associated with the oestrogen receptor positivity in breast carcinomas. CYP27B1 expression is slightly lower in invasive carcinomas (44.6%) than in benign lesions (55.8%). In contrast, CYP24A1 expression was augmented in carcinomas (56.0% in in situ and 53.7% in invasive carcinomas) when compared with that in benign lesions (19.0%). From this study, we conclude that there is a deregulation of the Vitamin D signalling and metabolic pathways in breast cancer, favouring tumour progression. Thus, during mammary malignant transformation, tumour cells lose their ability to synthesize the active form of Vitamin D and respond to VDR-mediated Vitamin D effects, while increasing their ability to degrade this hormone

Analysis of the effects of exposure to acute hypoxia on oxidative lesions and tumour progression in a transgenic mouse breast cancer model

Directory of Open Access Journals (Sweden)

Lunt Sarah

2008-05-01

Full Text Available Abstract Background Tumour hypoxia is known to be a poor prognostic indicator, predictive of increased risk of metastatic disease and reduced survival. Genomic instability has been proposed as one of the potential mechanisms for hypoxic tumour progression. Both of these features are commonly found in many cancer types, but their relationship and association with tumour progression has not been examined in the same model. Methods To address this issue, we determined the effects of 6 week in vivo acute hypoxic exposure on the levels of mutagenic lipid peroxidation product, malondialdehyde, and 8-oxo-7,8-dihydro-2'-deoxyguanosine DNA (8-oxo-dG lesions in the transgenic polyomavirus middle T (PyMT breast cancer mouse model. Results We observed significantly increased plasma lipid peroxidation and 8-oxo-dG lesion levels in the hypoxia-exposed mice. Consumption of malondialdehyde also induced a significant increase in the PyMT tumour DNA lesion levels, however, these increases did not translate into enhanced tumour progression. We further showed that the in vivo exposure to acute hypoxia induced accumulation of F4/80 positive tumour-associated macrophages (TAMs, demonstrating a relationship between hypoxia and macrophages in an experimental model. Conclusion These data suggest that although exposure to acute hypoxia causes an increase in 8-oxo-dG lesions and TAMs in the PyMT tumours, these increases do not translate into significant changes in tumour progression at the primary or metastatic levels in this strong viral oncogene-driven breast cancer model.

The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 1. Technical Report # 0919

Science.gov (United States)

Alonzo, Julie; Tindal, Gerald

2009-01-01

In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grade 1. These measures, available as part of easyCBM [TM], an online progress monitoring assessment system, were developed in 2008 and administered to approximately 2800 students from schools…

The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 2. Technical Report # 0920

Science.gov (United States)

Alonzo, Julie; Lai, Cheng Fei; Tindal, Gerald

2009-01-01

In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 7. Technical Report 0908

Science.gov (United States)

Lai, Cheng Fei; Alonzo, Julie; Tindal, Gerald

2009-01-01

In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

Regulation of in situ to invasive breast carcinoma transition

Energy Technology Data Exchange (ETDEWEB)

Polyak, Kornelia; Hu, Min; Yao, Jun; Carroll, Danielle K.; Weremowicz, Stanislawa; Chen, Haiyan; Carrasco, Daniel; Richardson, Andrea; Violette, Shelia; Gelman, Rebecca S.; Bissell, Mina J.; Schnitt, Stuart; Polyak, Kornelia

2008-05-07

The transition of ductal carcinoma in situ (DCIS) to invasive carcinoma is a key event in breast tumor progression that is poorly understood. Comparative molecular analysis of tumor epithelial cells from in situ and invasive tumors has failed to identify consistent tumor stage-specific differences. However, the myoepithelial cell layer, present only in DCIS, is a key distinguishing and diagnostic feature. To determine the contribution of non-epithelial cells to tumor progression, we analyzed the role of myoepithelial cells and fibroblasts in the progression of in situ carcinomas using a xenograft model of human DCIS. Progression to invasion was promoted by fibroblasts, but inhibited by normal myoepithelial cells. The invasive tumor cells from these progressed lesions formed DCIS rather than invasive cancers when re-injected into naive mice. Molecular profiles of myoepithelial and epithelial cells isolated from primary normal and cancerous human breast tissue samples corroborated findings obtained in the xenograft model. These results provide the proof of principle that breast tumor progression could occur in the absence of additional genetic alterations and that tumor growth and progression could be controlled by replacement of normal myoepithelial inhibitory signals.

Regulation of In Situ to Invasive Breast CarcinomaTransition

Energy Technology Data Exchange (ETDEWEB)

Hu, Min; Carroll, Danielle K.; Weremowicz, Stanislawa; Chen,Haiyan; Carrasco, Daniel; Richardson, Andrea; Bissell, Mina; Violette,Shelia; Gelman, Rebecca S.; Schnitt, Stuart; Polyak, Kornelia

2007-03-13

The transition of ductal carcinoma in situ (DCIS) to invasive carcinoma is a key event in breast tumor progression that is poorly understood. Comparative molecular analysis of tumor epithelial cells from in situ and invasive tumors has failed to identify consistent tumor stage-specific differences. However, the myoepithelial cell layer, present only in DCIS, is a key distinguishing and diagnostic feature. To determine the contribution of non-epithelial cells to tumor progression, we analyzed the role of myoepithelial cells and fibroblasts in the progression of in situ carcinomas using a xenograft model of human DCIS. Progression to invasion was promoted by fibroblasts, but inhibited by normal myoepithelial cells. The invasive tumor cells from these progressed lesions formed DCIS rather than invasive cancers when re-injected into naive mice. Molecular profiles of myoepithelial and epithelial cells isolated from primary normal and cancerous human breast tissue samples corroborated findings obtained in the xenograft model. These results provide the proof of principle that breast tumor progression could occur in the absence of additional genetic alterations and that tumor growth and progression could be controlled by replacement of normal myoepithelial inhibitory signals.

Technical reliability of geological disposal for high-level radioactive wastes in Japan. The second progress report. Introductory part and summaries

International Nuclear Information System (INIS)

1999-11-01

Based on the Advisory Committee Report on Nuclear Fuel Cycle Backend Policy submitted to the Japanese Government in 1997, JNC documents the progress of research and development program in the form of the second progress report (the first one published in 1992). It summarizes an evaluation of the technical reliability and safety of the geological disposal concept for high-level radioactive wastes (HLW) in Japan and comprises seven chapters. Chapter I briefly describes the importance of HLW management in promoting nuclear energy utilization. According to the long-term program, the HLW separated from spent fuels at reprocessing plants is to be vitrified and stored for a period of 30 to 50 years to allow cooling, then be disposed of in a deep geological formation. Chapter II mainly explains the concepts of geological disposal in Japan. Chapters III to V are devoted to discussions on three important technical elements (the geological environment of Japan, engineering technology and safety assessment of the geological disposal system) which are necessary for reliable realization of the geological disposal concept. Chapter VI demonstrates the technical ground for site selection and for setup of safety standards of the disposal. Chapter VII summarizes together with plans for future research and development. (Ohno, S.)

Analysis of breast cancer progression using principal component ...

Indian Academy of Sciences (India)

PRAKASH KUMAR

technology being aggressively pursued by researchers, ... public microarray breast cancer dataset which has expression levels of genes in normal samples as well as in three ..... suggests that treatment decisions may benefit by taking account ...

The role of dietary factors in prevention and progression of breast cancer.

Science.gov (United States)

Rossi, Roberta Elisa; Pericleous, Marinos; Mandair, Dalvinder; Whyand, Tara; Caplin, Martyn Evan

2014-12-01

Breast cancer (BC) is the leading global cause of cancer-related death in women. There is growing evidence for a role for dietary factors in BC pathophysiology. The aim of the present review was to evaluate the impact of dietary factors in BC risk. Bibliographical searches were performed in PubMed, using the following terms: "nutrition and breast cancer", "nutrition and breast carcinoma", "dietary factors and breast cancer", "risk factors and breast cancer", "diet and breast cancer, "breast cancer epidemiology", "breast cancer and prevention". Consumption of well-done red meat appears to be associated with increased risk of BC, whereas fish may be protective. Total cholesterol, triglyceride levels and glycaemic load should be monitored and controlled in at risk populations because they may be associated with increased risk of BC, although the exact mechanisms involved are not clear. Alcohol intake should be minimized since it is a risk factor for BC. High intake of polyphenol/phyto-oestrogen -rich food (i.e. flavonoids, soya products), as well as fibres, fruits and vegetables, may have potential protective effects against BC occurrence but the results might vary according to hormonal status. Vitamin D supplements appear protective against BC development and similarly other vitamins and oligo-elements might decrease BC risk, although further large prospective studies are required. There exist increasing evidence that dietary factors can play an important role in both the development and prevention of BC. Large randomized clinical and epidemiological studies are required but are difficult to design due to the number of variable factors. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

MR-Guided High-Intensity Focused Ultrasound Ablation of Breast Cancer with a Dedicated Breast Platform

International Nuclear Information System (INIS)

Merckel, Laura G.; Bartels, Lambertus W.; Köhler, Max O.; Bongard, H. J. G. Desirée van den; Deckers, Roel; Mali, Willem P. Th. M.; Binkert, Christoph A.; Moonen, Chrit T.; Gilhuijs, Kenneth G. A.; Bosch, Maurice A. A. J. van den

2013-01-01

Optimizing the treatment of breast cancer remains a major topic of interest. In current clinical practice, breast-conserving therapy is the standard of care for patients with localized breast cancer. Technological developments have fueled interest in less invasive breast cancer treatment. Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a completely noninvasive ablation technique. Focused beams of ultrasound are used for ablation of the target lesion without disrupting the skin and subcutaneous tissues in the beam path. MRI is an excellent imaging method for tumor targeting, treatment monitoring, and evaluation of treatment results. The combination of HIFU and MR imaging offers an opportunity for image-guided ablation of breast cancer. Previous studies of MR-HIFU in breast cancer patients reported a limited efficacy, which hampered the clinical translation of this technique. These prior studies were performed without an MR-HIFU system specifically developed for breast cancer treatment. In this article, a novel and dedicated MR-HIFU breast platform is presented. This system has been designed for safe and effective MR-HIFU ablation of breast cancer. Furthermore, both clinical and technical challenges are discussed, which have to be solved before MR-HIFU ablation of breast cancer can be implemented in routine clinical practice.

Evidence that breast tissue stiffness is associated with risk of breast cancer.

Science.gov (United States)

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

2014-01-01

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

Prolactin promotes breast cancer cell migration through actin cytoskeleton remodeling

Directory of Open Access Journals (Sweden)

Priscilla Ludovico da Silva

2015-12-01

Full Text Available The role of prolactin on breast cancer development and progression is debated. Breast cancer progression largely depends on cell movement and on the ability to remodel the actin cytoskeleton. In this process, actin-binding proteins are requested to achieve fibrillar actin de-polymerization and relocation at the cell membrane. Kinases such as focal adhesion kinase (FAK are later required to form actin/vinculin-enriched structures called focal adhesion complexes, which mediate firm adhesion to the extracellular matrix. These controllers are regulated by c-Src, which forms multiprotein signaling complexes with membrane receptors and is regulated by a number of hormones, including prolactin. We here show that breast cancer cells exposed to prolactin display an elevated c-Src expression and phosphorylation. In parallel, increased moesin and FAK expression and phosphorylation are found. These molecular changes are associated to relocation to the plasma membrane of cytoskeletal actin fibers and to increased horizontal cell movement. In conclusion, prolactin regulates actin remodeling and enhances breast cancer cell movement. This finding broadens the understanding of prolactin actions on breast cancer cells, highlighting new pathways that may be relevant to on breast cancer progression.

Tissue inhibitor of metalloproteinase-4 is elevated in early-stage breast cancers with accelerated progression and poor clinical course.

Science.gov (United States)

Liss, Michaelann; Sreedhar, Nandhini; Keshgegian, Albert; Sauter, Guido; Chernick, Michael R; Prendergast, George C; Wallon, U Margaretha

2009-09-01

An increasing number of breast cancer patients are diagnosed with small, localized, early-stage tumors. These patients are typically thought to have a good prognosis for long-term disease-free survival, but epidemiological studies indicate that up to 30% may have a recurrence within 3 to 5 years of diagnosis. Identifying patients with a high risk of recurrence and/or progression is important because they could be more aggressively treated at diagnosis to improve their chances for disease-free survival. Recent evidence suggests that elevated levels of the matrix metalloproteinase inhibitor, tissue inhibitor of metalloproteinase (TIMP)-4, are associated with malignant progression of ductal carcinoma in situ, a precancerous lesion. To examine the association of TIMP-4 with survival outcomes, we conducted a retrospective immunohistochemical analysis of 314 cases from patients with early-stage disease, defined as tumors smaller than 2 cm and no spread to lymph nodes (tumor-node-metastasis staging: T1N0MX). We found that tumors with elevated levels of TIMP-4 were correlated with a reduced probability of long-term disease-free survival, especially in patients with estrogen receptor-negative tumors. Our findings prompt further evaluation of TIMP-4 as a simple prognostic marker that may help identify patients with early-stage breast cancer who could benefit from more aggressive treatment at diagnosis.

Progresso tecnico, forme di mercato e disoccupazione. ( Technical progress, market forms and unemployment

Directory of Open Access Journals (Sweden)

A. ASIMAKOPULOS A.

2013-12-01

Full Text Available Lo scopo del presente lavoro è triplice . Il primo obiettivo è quello di sottolineare l'importanza delle intuizioni da trovare nel lavoro di Sylos Labini . Il secondo scopo è quello di espandere su di essa distinguendo tra i diversi tipi di progresso tecnico . Infine , il terzo obiettivo è quello di commentare il confronto di Labini di Ricardo e Keynes sulla possibilità di disoccupazione tecnologica . Per quanto riguarda la sua descrizione del progresso tecnologico come " risparmio di lavoro " , l'autore mostra che una descrizione più completa sarebbe più utile per i suoi scopiThe purpose of the present paper is threefold. The first purpose is to emphasise the importance of the insights to be found in Sylos Labini’s work. The second purpose is to expand upon it by distinguishing  between the different types of technical progress. Finally, the third purpose is to comment on Labini’s comparison of Ricardo and Keynes on the possibility of technological unemployment. Regarding his description of technological progress as “labour saving”, the author shows that a more comprehensive description would be more useful for his purposes.JEL: E24, J64, O33

Endocrine therapy for postmenopausal women with hormone receptor-positive her2-negative advanced breast cancer after progression or recurrence on nonsteroidal aromatase inhibitor therapy: a Canadian consensus statement.

Science.gov (United States)

Pritchard, K I; Gelmon, K A; Rayson, D; Provencher, L; Webster, M; McLeod, D; Verma, S

2013-02-01

Approximately 22,700 Canadian women were expected to be diagnosed with breast cancer in 2012. Despite improvements in screening and adjuvant treatment options, a substantial number of postmenopausal women with hormone receptor positive (hr+) breast cancer will continue to develop metastatic disease during or after adjuvant endocrine therapy. Guidance on the selection of endocrine therapy for patients with hr+ disease that is negative for the human epidermal growth factor receptor 2 (her2-) and that has relapsed or progressed on earlier nonsteroidal aromatase inhibitor (nsai) therapy is of increasing clinical importance. Exemestane, fulvestrant, and tamoxifen are approved therapeutic options in this context. Four phase iii trials involving 2876 patients-efect, sofea, confirm, and bolero-2-have assessed the efficacy of various treatment options in this clinical setting. Data from those trials suggest that standard-dose fulvestrant (250 mg monthly) and exemestane are of comparable efficacy, that doubling the dose of fulvestrant from 250 mg to 500 mg monthly results in a 15% reduction in the risk of progression, and that adding everolimus to exemestane (compared with exemestane alone) results in a 57% reduction in the risk of progression, albeit with increased toxicity. Multiple treatment options are now available to women with hr+ her2- advanced breast cancer recurring or progressing on earlier nsai therapy, although current clinical trial data suggest more robust clinical efficacy with everolimus plus exemestane. Consideration should be given to the patient's age, functional status, and comorbidities during selection of an endocrine therapy, and use of a proactive everolimus safety management strategy is encouraged.

Breast necrosis associated with thromboembolic disorders

International Nuclear Information System (INIS)

Andersson, I.; Adler, D.D.; Ljungberg, O.; Malmoe Allmaenna Sjukhus; Michigan Univ., Ann Arbor

1987-01-01

Two obese women with thrombotic disease complicated by necrosis of the breast are described. In one patient the reaction started after a few days of coumarin treatment and progressed to severe necrosis requiring mastectomy. The other patient was not on anticoagulant therapy when the breast reaction started and the clinical course was less severe. The radiographic appearance was characterized by thickening of the breast trabeculae, increased density of the breast and skin thickening. Although the radiographic findings are non-specific, the correct diagnosis can be suggested if combined with appropriate clinical information. The disease process may mimic breast cancer of the inflammatory type, clinically as well as radiographically. (orig.)

Technical progress and efficiency changes in football teams participating in the UEFA Champions League

Directory of Open Access Journals (Sweden)

Lucía Isabel García Cebrián

2015-09-01

Full Text Available This paper commits to calculate and analyze productivy levels and its components for teams that participated in the UEFA Champions League between 2003 and 2012. It will pursue three objectives: 1 evaluate resources usage, 2 analyze the productivity levels of the football teams and the sports results, and 3 see the influence of participation experience in reference to productivity and sports results. Using Malmquist Productivity Index, the results reflect a lack of consistent progression of efficiency, productivity, and technical change. This competition does not reward the efficient usage of resources and there is not a conclusive relationshop between permanence in the competition and productivity.

Volatiles combustion in fluidized beds. Technical progress report, 4 March 1993--3 June 1993

Energy Technology Data Exchange (ETDEWEB)

Hesketh, R.P.

1993-09-01

The goal of this project is to investigate the conditions in which volatiles will burn within both the dense and freeboard regions of fluidized beds. Experiments using a fluidized bed operated at incipient fluidization will be performed to characterize the effect of particle surface area, initial fuel concentration, and particle type on the inhibition of volatiles within a fluidized bed. The work conducted during the period 4 March, 1993 through 3 June, 1993 is reported in this technical progress report. The work during this time period consists primarily of the startup and trouble shooting of the fluidized bed reactor and gas phase modeling of methane and propane.

Progesterone receptor blockade in human breast cancer cells decreases cell cycle progression through G2/M by repressing G2/M genes.

Science.gov (United States)

Clare, Susan E; Gupta, Akash; Choi, MiRan; Ranjan, Manish; Lee, Oukseub; Wang, Jun; Ivancic, David Z; Kim, J Julie; Khan, Seema A

2016-05-23

The synthesis of specific, potent progesterone antagonists adds potential agents to the breast cancer prevention and treatment armamentarium. The identification of individuals who will benefit from these agents will be a critical factor for their clinical success. We utilized telapristone acetate (TPA; CDB-4124) to understand the effects of progesterone receptor (PR) blockade on proliferation, apoptosis, promoter binding, cell cycle progression, and gene expression. We then identified a set of genes that overlap with human breast luteal-phase expressed genes and signify progesterone activity in both normal breast cells and breast cancer cell lines. TPA administration to T47D cells results in a 30 % decrease in cell number at 24 h, which is maintained over 72 h only in the presence of estradiol. Blockade of progesterone signaling by TPA for 24 h results in fewer cells in G2/M, attributable to decreased expression of genes that facilitate the G2/M transition. Gene expression data suggest that TPA affects several mechanisms that progesterone utilizes to control gene expression, including specific post-translational modifications, and nucleosomal organization and higher order chromatin structure, which regulate access of PR to its DNA binding sites. By comparing genes induced by the progestin R5020 in T47D cells with those increased in the luteal-phase normal breast, we have identified a set of genes that predict functional progesterone signaling in tissue. These data will facilitate an understanding of the ways in which drugs such as TPA may be utilized for the prevention, and possibly the therapy, of human breast cancer.

Overexpression of a novel cell cycle regulator ecdysoneless in breast cancer: a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients.

Science.gov (United States)

Zhao, Xiangshan; Mirza, Sameer; Alshareeda, Alaa; Zhang, Ying; Gurumurthy, Channabasavaiah Basavaraju; Bele, Aditya; Kim, Jun Hyun; Mohibi, Shakur; Goswami, Monica; Lele, Subodh M; West, William; Qiu, Fang; Ellis, Ian O; Rakha, Emad A; Green, Andrew R; Band, Hamid; Band, Vimla

2012-07-01

Uncontrolled proliferation is one of the hallmarks of breast cancer. We have previously identified the human Ecd protein (human ortholog of Drosophila Ecdysoneless, hereafter called Ecd) as a novel promoter of mammalian cell cycle progression, a function related to its ability to remove the repressive effects of Rb-family tumor suppressors on E2F transcription factors. Given the frequent dysregulation of cell cycle regulatory components in human cancer, we used immunohistochemistry of paraffin-embedded tissues to examine Ecd expression in normal breast tissue versus tissues representing increasing breast cancer progression. Initial studies of a smaller cohort without outcomes information showed that Ecd expression was barely detectable in normal breast tissue and in hyperplasia of breast, but high levels of Ecd were detected in benign breast hyperplasia, ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDCs) of the breast. In this cohort of 104 IDC patients, Ecd expression levels showed a positive correlation with higher grade (P=0.04). Further analyses of Ecd expression using a larger, independent cohort (954) confirmed these results, with a strong positive correlation of elevated Ecd expression with higher histological grade (P=0.013), mitotic index (P=0.032), and Nottingham Prognostic Index score (P=0.014). Ecd expression was positively associated with HER2/neu (P=0.002) overexpression, a known marker of poor prognosis in breast cancer. Significantly, increased Ecd expression showed a strong positive association with shorter breast cancer specific survival (BCSS) (P=0.008) and disease-free survival (DFS) (P=0.003) in HER2/neu overexpressing patients. Taken together, our results reveal Ecd as a novel marker for breast cancer progression and show that levels of Ecd expression predict poorer survival in Her2/neu overexpressing breast cancer patients.

The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 3. Technical Report # 09-02

Science.gov (United States)

Alonzo, Julie; Lai, Cheng Fei; Tindal, Gerald

2009-01-01

In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 5. Technical Report # 09-01

Science.gov (United States)

Lai, Cheng Fei; Alonzo, Julie; Tindal, Gerald

2009-01-01

In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 4. Technical Report # 09-03

Science.gov (United States)

Alonzo, Julie; Lai, Cheng Fei; Tindal, Gerald

2009-01-01

In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 8. Technical Report # 09-04

Science.gov (United States)

Lai, Cheng Fei; Alonzo, Julie; Tindal, Gerald

2009-01-01

In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

A clinical randomized controlled trial of music therapy and progressive muscle relaxation training in female breast cancer patients after radical mastectomy: results on depression, anxiety and length of hospital stay.

Science.gov (United States)

Zhou, Kaina; Li, Xiaomei; Li, Jin; Liu, Miao; Dang, Shaonong; Wang, Duolao; Xin, Xia

2015-02-01

To examine effects of music therapy and progressive muscle relaxation training on depression, anxiety and length of hospital stay in Chinese female breast cancer patients after radical mastectomy. A total of 170 patients were randomly allocated to the intervention group (n = 85) receiving music therapy and progressive muscle relaxation training plus routine nursing care and the control group (n = 85) receiving routine nursing care. Music therapy and progressive muscle relaxation training were performed twice a day within 48 h after radical mastectomy, once in the early morning (6a.m.-8a.m.) and once in the evening (9p.m.-11p.m.), for 30 min per session until discharged from the hospital. A general linear model with univariate analysis showed that the intervention group patients had significant improvement in depression and anxiety in the effects of group (F = 20.31, P Music therapy and progressive muscle relaxation training can reduce depression, anxiety and length of hospital stay in female breast cancer patients after radical mastectomy. Copyright © 2014 Elsevier Ltd. All rights reserved.

National Council on Radiation Protection and Measurements semiannual technical progress report, March 1989--August 1989

International Nuclear Information System (INIS)

Ney, W.R.

1991-01-01

This semiannual technical progress report is for the period 1 March 1989 through 31 August 1989. This National Council on Radiation Protection and Measurements (NCRP) program is designed to provide recommendations for radiation protection based on scientific principles. During this period several reports were published covering the topics of occupational radiation exposure, medical exposure, radon control, dosimetry, and radiation protection standards. Accomplishments of various committees are also reported; including the committees on dental x-ray protection, radiation safety in uranium mining and milling, ALARA, instrumentation, records maintenance, occupational exposures of medical personnel, emergency planning, and others. (SM)

Index to Nuclear Safety: a technical progress review by chronology, permuted title, and author, Volume 18 (1) through Volume 22 (6)

International Nuclear Information System (INIS)

Cottrell, W.B.; Passiakos, M.

1982-06-01

This index to Nuclear Safety covers articles published in Nuclear Safety, Volume 18, Number 1 (January-February 1977) through Volume 22, Number 6 (November-December 1981). The index is divided into three section: a chronological list of articles (including abstracts), a permuted-title (KWIC) index, and an author index. Nuclear Safety, a bimonthly technical progress review prepared by the Nuclear Safety Information Center, covers all safety aspects of nuclear power reactors and associated facilities. Over 300 technical articles published in Nuclear Safety in the last 5 years are listed in this index

Index to Nuclear Safety: a technical progress review by chronology, permuted title, and author, Volume 18 (1) through Volume 22 (6)

Energy Technology Data Exchange (ETDEWEB)

Cottrell, W.B.; Passiakos, M.

1982-06-01

This index to Nuclear Safety covers articles published in Nuclear Safety, Volume 18, Number 1 (January-February 1977) through Volume 22, Number 6 (November-December 1981). The index is divided into three section: a chronological list of articles (including abstracts), a permuted-title (KWIC) index, and an author index. Nuclear Safety, a bimonthly technical progress review prepared by the Nuclear Safety Information Center, covers all safety aspects of nuclear power reactors and associated facilities. Over 300 technical articles published in Nuclear Safety in the last 5 years are listed in this index.

[Elastography as an additional tool in breast sonography. Technical principles and clinical applications].

Science.gov (United States)

Rjosk-Dendorfer, D; Reichelt, A; Clevert, D-A

2014-03-01

In recent years the use of elastography in addition to sonography has become a routine clinical tool for the characterization of breast masses. Whereas free hand compression elastography results in qualitative imaging of tissue stiffness due to induced compression, shear wave elastography displays quantitative information of tissue displacement. Recent studies have investigated the use of elastography in addition to sonography and improvement of specificity in differentiating benign from malignant breast masses could be shown. Therefore, additional use of elastography could help to reduce the number of unnecessary biopsies in benign breast lesions especially in category IV lesions of the ultrasound breast imaging reporting data system (US-BI-RADS).

EXPRESSION AND SIGNIFICANCE OF ERK PROTEIN IN HUMAN BREAST CARCINOMA

Institute of Scientific and Technical Information of China (English)

张秀梅; 李柏林; 宋敏; 宋继谒

2004-01-01

Objective: To investigate the expression of ERK and p-ERK protein in human breast cancer and their corresponding tissue, to assess the significance of ERK signal pathway in tumorigenesis and progression of breast carcinoma. Methods: 40 breast cancer cases were used in S-P immunohistochemistry technique and Western Blot study. Results: The expression of ERK1, ERK2, and p- ERK protein levels increased remarkably in breast cancer tissues in comparison to normal tissues (P<0.01). The expression was upregulated by 1.32-, 1.53-and 4.27-fold, respectively. The overexpressions of ERK1, ERK2, and p- ERK proteins were obviously correlated with clinical stage of breast cancer. Protein levels of ERK and p-ERK were higher in stage III patients than in stage I and stage II patients (P<0.05). These proteins were strongly related with axillary lymph node metastasis of breast cancer, but not correlated with histopathological type and status of ER and PR of breast cancer. Expression of ERK1, and ERK2, protein showed a positive linear correlation. Conclusion: ERK signal transduction pathway is a key factor during human breast tumorigenesis and breast cancer progression.

Index to Nuclear Safety. A technical progress review by chronology, permuted title, and author. Vol. 11, No. 1--Vol. 17, No. 6

International Nuclear Information System (INIS)

Cottrell, W.B.; Klein, A.

1977-01-01

This index to Nuclear Safety covers articles in Nuclear Safety Vol. 11, No. 1 (Jan.-Feb. 1970), through Vol. 17, No. 6 (Nov.-Dec. 1976). The index includes a chronological list of articles (including abstract) followed by KWIC and Author Indexes. Nuclear Safety, a bimonthly technical progress review prepared by the Nuclear Safety Information Center, covers all safety aspects of nuclear power reactors and associated facilities. The index lists over 350 technical articles in the last six years of publication

Index to Nuclear Safety. A technical progress review by chronology, permuted title, and author. Vol. 11, No. 1--Vol. 17, No. 6

Energy Technology Data Exchange (ETDEWEB)

Cottrell, W.B.; Klein, A.

1977-02-23

This index to Nuclear Safety covers articles in Nuclear Safety Vol. 11, No. 1 (Jan.-Feb. 1970), through Vol. 17, No. 6 (Nov.-Dec. 1976). The index includes a chronological list of articles (including abstract) followed by KWIC and Author Indexes. Nuclear Safety, a bimonthly technical progress review prepared by the Nuclear Safety Information Center, covers all safety aspects of nuclear power reactors and associated facilities. The index lists over 350 technical articles in the last six years of publication.

The compressed breast during mammography and breast tomosynthesis: in vivo shape characterization and modeling

Science.gov (United States)

Rodríguez-Ruiz, Alejandro; Agasthya, Greeshma A.; Sechopoulos, Ioannis

2017-09-01

To characterize and develop a patient-based 3D model of the compressed breast undergoing mammography and breast tomosynthesis. During this IRB-approved, HIPAA-compliant study, 50 women were recruited to undergo 3D breast surface imaging with structured light (SL) during breast compression, along with simultaneous acquisition of a tomosynthesis image. A pair of SL systems were used to acquire 3D surface images by projecting 24 different patterns onto the compressed breast and capturing their reflection off the breast surface in approximately 12-16 s. The 3D surface was characterized and modeled via principal component analysis. The resulting surface model was combined with a previously developed 2D model of projected compressed breast shapes to generate a full 3D model. Data from ten patients were discarded due to technical problems during image acquisition. The maximum breast thickness (found at the chest-wall) had an average value of 56 mm, and decreased 13% towards the nipple (breast tilt angle of 5.2°). The portion of the breast not in contact with the compression paddle or the support table extended on average 17 mm, 18% of the chest-wall to nipple distance. The outermost point along the breast surface lies below the midline of the total thickness. A complete 3D model of compressed breast shapes was created and implemented as a software application available for download, capable of generating new random realistic 3D shapes of breasts undergoing compression. Accurate characterization and modeling of the breast curvature and shape was achieved and will be used for various image processing and clinical tasks.

Endocrine therapy for postmenopausal women with hormone receptor–positive her2–negative advanced breast cancer after progression or recurrence on nonsteroidal aromatase inhibitor therapy: a Canadian consensus statement

Science.gov (United States)

Pritchard, K.I.; Gelmon, K.A.; Rayson, D.; Provencher, L.; Webster, M.; McLeod, D.; Verma, S.

2013-01-01

Approximately 22,700 Canadian women were expected to be diagnosed with breast cancer in 2012. Despite improvements in screening and adjuvant treatment options, a substantial number of postmenopausal women with hormone receptor positive (hr+) breast cancer will continue to develop metastatic disease during or after adjuvant endocrine therapy. Guidance on the selection of endocrine therapy for patients with hr+ disease that is negative for the human epidermal growth factor receptor 2 (her2–) and that has relapsed or progressed on earlier nonsteroidal aromatase inhibitor (nsai) therapy is of increasing clinical importance. Exemestane, fulvestrant, and tamoxifen are approved therapeutic options in this context. Four phase iii trials involving 2876 patients—efect, sofea, confirm, and bolero-2—have assessed the efficacy of various treatment options in this clinical setting. Data from those trials suggest that standard-dose fulvestrant (250 mg monthly) and exemestane are of comparable efficacy, that doubling the dose of fulvestrant from 250 mg to 500 mg monthly results in a 15% reduction in the risk of progression, and that adding everolimus to exemestane (compared with exemestane alone) results in a 57% reduction in the risk of progression, albeit with increased toxicity. Multiple treatment options are now available to women with hr+ her2– advanced breast cancer recurring or progressing on earlier nsai therapy, although current clinical trial data suggest more robust clinical efficacy with everolimus plus exemestane. Consideration should be given to the patient’s age, functional status, and comorbidities during selection of an endocrine therapy, and use of a proactive everolimus safety management strategy is encouraged. PMID:23443928

Initial results of the FUSION-X-US prototype combining 3D automated breast ultrasound and digital breast tomosynthesis.

Science.gov (United States)

Schaefgen, Benedikt; Heil, Joerg; Barr, Richard G; Radicke, Marcus; Harcos, Aba; Gomez, Christina; Stieber, Anne; Hennigs, André; von Au, Alexandra; Spratte, Julia; Rauch, Geraldine; Rom, Joachim; Schütz, Florian; Sohn, Christof; Golatta, Michael

2018-06-01

To determine the feasibility of a prototype device combining 3D-automated breast ultrasound (ABVS) and digital breast tomosynthesis in a single device to detect and characterize breast lesions. In this prospective feasibility study, the FUSION-X-US prototype was used to perform digital breast tomosynthesis and ABVS in 23 patients with an indication for tomosynthesis based on current guidelines after clinical examination and standard imaging. The ABVS and tomosynthesis images of the prototype were interpreted separately by two blinded experts. The study compares the detection and BI-RADS® scores of breast lesions using only the tomosynthesis and ABVS data from the FUSION-X-US prototype to the results of the complete diagnostic workup. Image acquisition and processing by the prototype was fast and accurate, with some limitations in ultrasound coverage and image quality. In the diagnostic workup, 29 solid lesions (23 benign, including three cases with microcalcifications, and six malignant lesions) were identified. Using the prototype, all malignant lesions were detected and classified as malignant or suspicious by both investigators. Solid breast lesions can be localized accurately and fast by the Fusion-X-US system. Technical improvements of the ultrasound image quality and ultrasound coverage are needed to further study this new device. The prototype combines tomosynthesis and automated 3D-ultrasound (ABVS) in one device. It allows accurate detection of malignant lesions, directly correlating tomosynthesis and ABVS data. The diagnostic evaluation of the prototype-acquired data was interpreter-independent. The prototype provides a time-efficient and technically reliable diagnostic procedure. The combination of tomosynthesis and ABVS is a promising diagnostic approach.

Localized morphea after breast implant for breast cancer: A case report.

Science.gov (United States)

Moretti, A; Bianchi, F; Abbate, I V; Gherardi, G; Bonavita, M; Passoni, E; Nazzaro, G; Bramati, A; Dazzani, M C; Piva, S; Paternò, E; Frungillo, N; Farina, G; La Verde, N

2018-03-01

Early breast cancer follow-up guidelines for patients who underwent surgery suggest a regular and accurate clinical examination of the breast area, for an early identification of cutaneous or subcutaneous breast cancer relapse. Nonetheless, breast skin lesions arising in patients treated with mastectomy for breast cancer can be caused by several diseases. A series of diagnostic hypotheses should be considered, not only focusing on cutaneous metastasis, but also on dermatologic and systemic diseases. In February 2015, a 37-year-old patient underwent a right subcutaneous mastectomy for stage IIA breast cancer. Five months after beginning adjuvant chemotherapy, she noted hyperpigmentation and thickening of the skin on the right breast. Differential diagnosis included local relapse, skin infection, lymphoma, or primary cutaneous disease, and a skin biopsy was performed. The histopathologic specimen showed full-thickness sclerosis, with features of localized morphea. Therapy with clobetasol was prescribed, with progressive resolution of the thickness. The collaboration between many professionals in a multidisciplinary team (oncologist, dermatologist, plastic surgeon, and pathologist) was crucial to achieving the diagnosis. In the literature, some articles describe correlation between connective tissue diseases and silicone breast implants, but the pathogenetic mechanisms are unknown. We report a rare case of breast morphea after positioning a silicone implant in a patient who had undergone mastectomy. This clinical report represents an interesting model of multidisciplinary management of a patient with breast cancer who developed an uncommon dermatologic disease. Further studies are needed to clarify the association between silicone implants and breast morphea.

Breast conserving surgery in locoregional treatment of breast carcinoma after Hodgkin lymphoma

International Nuclear Information System (INIS)

Haberer, S.; Le Scodan, R.; Kirova, Y.M.; Moisson, P.; Campana, F.; Fourquet, A.; Bollet, M.A.; Belin, L.; Savignoni, A.; Stevens, D.; Decaudin, D.; Pierga, J.Y.; Reyal, F.

2012-01-01

Purpose. - To report characteristics and outcome of breast cancer after irradiation for Hodgkin lymphoma with special focus on breast conservation surgery. Patients and methods. - Medical records of 72 women who developed either ductal carcinoma in situ or stage I-III invasive carcinoma of the breast after Hodgkin lymphoma between 1978 and 2009 were retrospectively reviewed. Results. - Median age at Hodgkin lymphoma diagnosis was 23 years old. Median total dose received by the mediastinum was 40 Gy, mostly by a mantle field technique. Breast cancer occurred after a median time interval of 21 years. Ductal invasive carcinoma and ductal carcinoma in situ represented respectively 71% and 19% of the cases. Locoregional treatment for breast cancer consisted of mastectomy with or without radiotherapy in 39 patients and of lumpectomy with or without adjuvant radiotherapy in 32 patients. The isocentric lateral decubitus radiation technique was used in 17 patients after breast conserving surgery (57%). With a median follow-up of 7 years, 5-year overall survival rate and locoregional control rate were respectively 74.5% and 82% for invasive carcinoma and 100% and 92% for in situ carcinoma. Thirteen patients died of progressive breast cancer and contralateral breast cancer was diagnosed in ten patients (14%). Conclusions. - Breast conserving treatment can be an option for breast cancers that occur after Hodgkin lymphoma despite prior thoracic irradiation. It should consist of lumpectomy and adjuvant breast radiotherapy with use of adequate techniques, such as the lateral decubitus isocentric position. (authors)

Altered serotonin physiology in human breast cancers favors paradoxical growth and cell survival.

Science.gov (United States)

Pai, Vaibhav P; Marshall, Aaron M; Hernandez, Laura L; Buckley, Arthur R; Horseman, Nelson D

2009-01-01

The breast microenvironment can either retard or accelerate the events associated with progression of latent cancers. However, the actions of local physiological mediators in the context of breast cancers are poorly understood. Serotonin (5-HT) is a critical local regulator of epithelial homeostasis in the breast and other organs. Herein, we report complex alterations in the intrinsic mammary gland serotonin system of human breast cancers. Serotonin biosynthetic capacity was analyzed in human breast tumor tissue microarrays using immunohistochemistry for tryptophan hydroxylase 1 (TPH1). Serotonin receptors (5-HT1-7) were analyzed in human breast tumors using the Oncomine database. Serotonin receptor expression, signal transduction, and 5-HT effects on breast cancer cell phenotype were compared in non-transformed and transformed human breast cells. In the context of the normal mammary gland, 5-HT acts as a physiological regulator of lactation and involution, in part by favoring growth arrest and cell death. This tightly regulated 5-HT system is subverted in multiple ways in human breast cancers. Specifically, TPH1 expression undergoes a non-linear change during progression, with increased expression during malignant progression. Correspondingly, the tightly regulated pattern of 5-HT receptors becomes dysregulated in human breast cancer cells, resulting in both ectopic expression of some isoforms and suppression of others. The receptor expression change is accompanied by altered downstream signaling of 5-HT receptors in human breast cancer cells, resulting in resistance to 5-HT-induced apoptosis, and stimulated proliferation. Our data constitutes the first report of direct involvement of 5-HT in human breast cancer. Increased 5-HT biosynthetic capacity accompanied by multiple changes in 5-HT receptor expression and signaling favor malignant progression of human breast cancer cells (for example, stimulated proliferation, inappropriate cell survival). This occurs

Enhancer of the rudimentary gene homologue (ERH expression pattern in sporadic human breast cancer and normal breast tissue

Directory of Open Access Journals (Sweden)

Knüchel Ruth

2008-05-01

Full Text Available Abstract Background The human gene ERH (Enhancer of the Rudimentary gene Homologue has previously been identified by in silico analysis of four million ESTs as a gene differentially expressed in breast cancer. The biological function of ERH protein has not been fully elucidated, however functions in cell cycle progression, pyrimidine metabolism a possible interaction with p21(Cip1/Waf1 via the Ciz1 zinc finger protein have been suggested. The aim of the present study was a systematic characterization of ERH expression in human breast cancer in order to evaluate possible clinical applications of this molecule. Methods The expression pattern of ERH was analyzed using multiple tissue northern blots (MTN on a panel of 16 normal human tissues and two sets of malignant/normal breast and ovarian tissue samples. ERH expression was further analyzed in breast cancer and normal breast tissues and in tumorigenic as well as non-tumorigenic breast cancer cell lines, using quantitative RT-PCR and non-radioisotopic in situ hybridization (ISH. Results Among normal human tissues, ERH expression was most abundant in testis, heart, ovary, prostate, and liver. In the two MTN sets of malignant/normal breast and ovarian tissue,ERH was clearly more abundantly expressed in all tumours than in normal tissue samples. Quantitative RT-PCR analyses showed that ERH expression was significantly more abundant in tumorigenic than in non-tumorigenic breast cancer cell lines (4.5-fold; p = 0.05, two-tailed Mann-Whitney U-test; the same trend was noted in a set of 25 primary invasive breast cancers and 16 normal breast tissue samples (2.5-fold; p = 0.1. These findings were further confirmed by non-radioisotopic ISH in human breast cancer and normal breast tissue. Conclusion ERH expression is clearly up-regulated in malignant as compared with benign breast cells both in primary human breast cancer and in cell models of breast cancer. Since similar results were obtained for ovarian

Early impact of social isolation and breast tumor progression in mice.

Science.gov (United States)

Madden, Kelley S; Szpunar, Mercedes J; Brown, Edward B

2013-03-01

Evidence from cancer patients and animal models of cancer indicates that exposure to psychosocial stress can promote tumor growth and metastasis, but the pathways underlying stress-induced cancer pathogenesis are not fully understood. Social isolation has been shown to promote tumor progression. We examined the impact of social isolation on breast cancer pathogenesis in adult female severe combined immunodeficiency (SCID) mice using the human breast cancer cell line, MDA-MB-231, a high β-adrenergic receptor (AR) expressing line. When group-adapted mice were transferred into single housing (social isolation) one week prior to MB-231 tumor cell injection into a mammary fat pad (orthotopic), no alterations in tumor growth or metastasis were detected compared to group-housed mice. When social isolation was delayed until tumors were palpable, tumor growth was transiently increased in singly-housed mice. To determine if sympathetic nervous system activation was associated with increased tumor growth, spleen and tumor norepinephrine (NE) was measured after social isolation, in conjunction with tumor-promoting macrophage populations. Three days after transfer to single housing, spleen weight was transiently increased in tumor-bearing and non-tumor-bearing mice in conjunction with reduced splenic NE concentration and elevated CD11b+Gr-1+ macrophages. At day 10 after social isolation, no changes in spleen CD11b+ populations or NE were detected in singly-housed mice. In the tumors, social isolation increased CD11b+Gr-1+, CD11b+Gr-1-, and F4/80+ macrophage populations, with no change in tumor NE. The results indicate that a psychological stressor, social isolation, elicits dynamic but transient effects on macrophage populations that may facilitate tumor growth. The transiency of the changes in peripheral NE suggest that homeostatic mechanisms may mitigate the impact of social isolation over time. Studies are underway to define the neuroendocrine mechanisms underlying the

Cytogenetic report of a male breast cancer

DEFF Research Database (Denmark)

Cavalli, L R; Rogatto, S R; Rainho, C A

1995-01-01

of chromosome 8 in the characterization of the subtype of ductal breast carcinomas and demonstrate that chromosome 17, which is frequently involved in female breast cancers, is also responsible for the development or progression of primary breast cancers in males.......The cytogenetic findings on G-banding in an infiltrating ductal breast carcinoma in a 69-year-old man are reported. The main abnormalities observed were trisomy of chromosomes 8 and 9 and structural rearrangement in the long arm of chromosome 17 (add(17)(q25)). Our results confirm the trisomy...

Progress in nonviral gene therapy for breast cancer and what comes next?

Science.gov (United States)

Bottai, Giulia; Truffi, Marta; Corsi, Fabio; Santarpia, Libero

2017-05-01

The possibility of correcting defective genes and modulating gene expression through gene therapy has emerged as a promising treatment strategy for breast cancer. Furthermore, the relevance of tumor immune microenvironment in supporting the oncogenic process has paved the way for novel immunomodulatory applications of gene therapy. Areas covered: In this review, the authors describe the most relevant delivery systems, focusing on nonviral vectors, along with the description of the major approaches used to modify target cells, including gene transfer, RNA interference (RNAi), and epigenetic regulation. Furthermore, they highlight innovative therapeutic strategies and the application of gene therapy in clinical trials for breast cancer. Expert opinion: Gene therapy has the potential to impact breast cancer research. Further efforts are required to increase the clinical application of RNAi-based therapeutics, especially in combination with conventional treatments. Innovative strategies, including genome editing and stem cell-based systems, may contribute to translate gene therapy into clinical practice. Immune-based approaches have emerged as an attractive therapeutic opportunity for selected breast cancer patients. However, several challenges need to be addressed before considering gene therapy as an actual option for the treatment of breast cancer.

Computed tomography of the breast cancer

International Nuclear Information System (INIS)

Chung, Soo Young; Lee, Yul; Bae, Sang Hoon; Yoon, Jong Sup; Lee, Ki Chu

1985-01-01

The indication of computed tomography for the breast lesion are 1) Unusually extensive or small breast caused technical difficulties in performing mammograms. 2) Questionable mammographic findings, especially in dense proliferative breast parenchyme. 3) Microcancer. 4) Suspicious regional lymph node enlargement or invasive of the chest wall by breast cancer. The diagnosis of breast CT in breast cancer is based on pathologic anatomic changes and characteristic increase of mean CT No. of lesion following contrast enhancement. Authors analysed CT of the 34 patients who were clinically suspected breast cancer, and compared with mammography. The results are as follows: 1. Pathological diagnosis of 34 cases were 27 cases of breast cancer, 4 cases of fibrocystic disease, 2 cases of fibroadenoma, and 1 case of intraductal papilloma. The diagnostic accuracy of CT in 27 breast cancer was 93% (25 cases) and mammography 71% (19 case). 2. Correct diagnosis of CT in 7 benign breast disease is in 5 cases and mammography in 5 cases. 3. The most important finding of CT in breast cancer is characteristic increase of CT No. of lesion following contrast enhancement (200 ml, 65%): over average 50 HU in 19 cases of 27 breast cancers, 30-50 HU in a 6 cases, 20-30 HU in 2 cases with tumor necrosis. 4. Computed with mammography, other more valuable CT findings of breast cancer are axillary lymph node enlargement and adjacentic pectoral muscle invasion. 5. In conclusion, breast CT is considered as valuable diagnostic tool in evaluation of breast cancer, but not of benign breast disease

Computed tomography of the breast cancer

Energy Technology Data Exchange (ETDEWEB)

Chung, Soo Young; Lee, Yul; Bae, Sang Hoon; Yoon, Jong Sup; Lee, Ki Chu [Hallym University Medical Center, Seoul (Korea, Republic of)

1985-12-15

The indication of computed tomography for the breast lesion are 1) Unusually extensive or small breast caused technical difficulties in performing mammograms. 2) Questionable mammographic findings, especially in dense proliferative breast parenchyme. 3) Microcancer. 4) Suspicious regional lymph node enlargement or invasive of the chest wall by breast cancer. The diagnosis of breast CT in breast cancer is based on pathologic anatomic changes and characteristic increase of mean CT No. of lesion following contrast enhancement. Authors analysed CT of the 34 patients who were clinically suspected breast cancer, and compared with mammography. The results are as follows: 1. Pathological diagnosis of 34 cases were 27 cases of breast cancer, 4 cases of fibrocystic disease, 2 cases of fibroadenoma, and 1 case of intraductal papilloma. The diagnostic accuracy of CT in 27 breast cancer was 93% (25 cases) and mammography 71% (19 case). 2. Correct diagnosis of CT in 7 benign breast disease is in 5 cases and mammography in 5 cases. 3. The most important finding of CT in breast cancer is characteristic increase of CT No. of lesion following contrast enhancement (200 ml, 65%): over average 50 HU in 19 cases of 27 breast cancers, 30-50 HU in a 6 cases, 20-30 HU in 2 cases with tumor necrosis. 4. Computed with mammography, other more valuable CT findings of breast cancer are axillary lymph node enlargement and adjacentic pectoral muscle invasion. 5. In conclusion, breast CT is considered as valuable diagnostic tool in evaluation of breast cancer, but not of benign breast disease.

Ultrasound guided pectoral nerve blockade versus thoracic spinal blockade for conservative breast surgery in cancer breast: A randomized controlled trial

Directory of Open Access Journals (Sweden)

Hala M.S. ELdeen

2016-01-01

Conclusion: In conclusion, both Pecs and TSB provide effective intraoperative anesthesia and prolonged postoperative pain relief after breast surgery, but the Pecs block is technically simple and easy to learn with few contraindications, provides hemodynamic stability, and has a low complication rate and it is therefore a safe and effective technique in performing intraoperative anesthesia and controlling postoperative pain after unilateral conservative breast surgery.

Progress report : Technical Physics Division

International Nuclear Information System (INIS)

Gopalaraman, C.P.; Deshpande, R.Y.

1978-01-01

The research and development work carried out in the Technical Physics Division of the Bhabha Atomic Research Centre, Bombay, is reported. Some of the achievements are: (1) fabrication of mass spectrometers for heavy water analysis and lithium 6/7 isotope ratio measurement, (2) fabrication of electronic components for mass spectrometers, (3) growing of sodium iodide crystals for radiation detectors, (4) development of sandwich detectors comprising of NaI(Tl) and CaI(Na), (5) fabrication of mass spectrometer type leak detectors and (6) fabrication of the high vacuum components of the vacuum system of the variable energy cyclotron based at Calcutta. (M.G.B.)

Progesterone receptor blockade in human breast cancer cells decreases cell cycle progression through G2/M by repressing G2/M genes

OpenAIRE

Clare, Susan E.; Gupta, Akash; Choi, MiRan; Ranjan, Manish; Lee, Oukseub; Wang, Jun; Ivancic, David Z.; Kim, J. Julie; Khan, Seema A.

2016-01-01

Background The synthesis of specific, potent progesterone antagonists adds potential agents to the breast cancer prevention and treatment armamentarium. The identification of individuals who will benefit from these agents will be a critical factor for their clinical success. Methods We utilized telapristone acetate (TPA; CDB-4124) to understand the effects of progesterone receptor (PR) blockade on proliferation, apoptosis, promoter binding, cell cycle progression, and gene expression. We then...

Breast anatomy, physiology and pathology for the physicist

International Nuclear Information System (INIS)

Watson, A.B.

1996-01-01

Increased awareness of the importance of early breast cancer detection has spurred improvements in mammographic imaging systems and has lead to an ever-increasing role for the medical physicist. This talk will review the anatomy, physiology and pathology of the breast and discuss from a clinician's viewpoint, the proper technical and processing factors required to produce a quality mammographic study. Correct breast positioning for the MLO and CC views, adequate compression, elimination fo motion artifacts, appropriate film density and other important factors that contribute to an optimal diagnostic mammogram will also be examined. (author)

Antiangiogenic therapy in breast cancer

OpenAIRE

Gampenrieder, Simon Peter; Westphal, Theresa; Greil, Richard

2017-01-01

Summary Based on a strong rationale for anti-VEGF (vascular endothelial growth factor) treatment in breast cancer and promising preclinical data, great hopes have been placed on the anti-VEGF antibody bevacizumab. Clinical trials, however, reported conflicting results. In metastatic human epidermal growth factor receptor 2(HER2)-negative breast cancer, the addition of bevacizumab to standard chemotherapy improved consistently progression-free survival (PFS), however, without effect on overall...

Human Breast Cancer Histoid

Science.gov (United States)

Kaur, Pavinder; Ward, Brenda; Saha, Baisakhi; Young, Lillian; Groshen, Susan; Techy, Geza; Lu, Yani; Atkinson, Roscoe; Taylor, Clive R.; Ingram, Marylou

2011-01-01

Progress in our understanding of heterotypic cellular interaction in the tumor microenvironment, which is recognized to play major roles in cancer progression, has been hampered due to unavailability of an appropriate in vitro co-culture model. The aim of this study was to generate an in vitro 3-dimensional human breast cancer model, which consists of cancer cells and fibroblasts. Breast cancer cells (UACC-893) and fibroblasts at various densities were co-cultured in a rotating suspension culture system to establish co-culture parameters. Subsequently, UACC-893, BT.20, or MDA.MB.453 were co-cultured with fibroblasts for 9 days. Co-cultures resulted in the generation of breast cancer histoid (BCH) with cancer cells showing the invasion of fibroblast spheroids, which were visualized by immunohistochemical (IHC) staining of sections (4 µm thick) of BCH. A reproducible quantitative expression of C-erbB.2 was detected in UACC-893 cancer cells in BCH sections by IHC staining and the Automated Cellular Imaging System. BCH sections also consistently exhibited qualitative expression of pancytokeratins, p53, Ki-67, or E-cadherin in cancer cells and that of vimentin or GSTPi in fibroblasts, fibronectin in the basement membrane and collagen IV in the extracellular matrix. The expression of the protein analytes and cellular architecture of BCH were markedly similar to those of breast cancer tissue. PMID:22034518

Benign breast myoepithelioma

Directory of Open Access Journals (Sweden)

L Khan

2013-01-01

Full Text Available Myoepithelioma of the breast is very rare. Breast myoepithelioma can develop in women from their early 20s right up to their 80s, but it is most common in women over 50. We report a case of 20-year-old female, who presented with a well-defined breast lump of 3 × 3 cm in size. Fine needle aspiration was performed. The cytological findings revealed good cellularity comprising monomorphic loosely cohesive sheets of plasmacytoid, round to polygonal cells with round to ovoid eccentrically placed nuclei, finely dispersed chromatin, and moderate amount of cytoplasm. On the basis of cytological findings, a diagnosis of benign myoepithelioma (plasmacytoid type was made which was confirmed on histopathologic examination. The breast is a very rare localization for this type of tumor. The benign character of the disease in conjunction with its slow progression could delay its detection and diagnosis. A detailed pathology examination is a prerequisite for avoidance of misleading diagnosis.

Solar lease grant program. Technical progress report

Energy Technology Data Exchange (ETDEWEB)

1981-04-01

Progress on a lease program for the installation of a solar water heater with no installation charge is reported. Information on the announcement of the program, the selection of participants, the contractural agreement, progress on installation of equipment, monitoring, and evaluation is summarized. The status of the budget concerned with the program is announced. Forms used for applications for the program and an announcement from Resource Alternatives for Cilco customers are presented.

Progesterone receptor blockade in human breast cancer cells decreases cell cycle progression through G2/M by repressing G2/M genes

International Nuclear Information System (INIS)

Clare, Susan E.; Gupta, Akash; Choi, MiRan; Ranjan, Manish; Lee, Oukseub; Wang, Jun; Ivancic, David Z.; Kim, J. Julie; Khan, Seema A.

2016-01-01

The synthesis of specific, potent progesterone antagonists adds potential agents to the breast cancer prevention and treatment armamentarium. The identification of individuals who will benefit from these agents will be a critical factor for their clinical success. We utilized telapristone acetate (TPA; CDB-4124) to understand the effects of progesterone receptor (PR) blockade on proliferation, apoptosis, promoter binding, cell cycle progression, and gene expression. We then identified a set of genes that overlap with human breast luteal-phase expressed genes and signify progesterone activity in both normal breast cells and breast cancer cell lines. TPA administration to T47D cells results in a 30 % decrease in cell number at 24 h, which is maintained over 72 h only in the presence of estradiol. Blockade of progesterone signaling by TPA for 24 h results in fewer cells in G2/M, attributable to decreased expression of genes that facilitate the G2/M transition. Gene expression data suggest that TPA affects several mechanisms that progesterone utilizes to control gene expression, including specific post-translational modifications, and nucleosomal organization and higher order chromatin structure, which regulate access of PR to its DNA binding sites. By comparing genes induced by the progestin R5020 in T47D cells with those increased in the luteal-phase normal breast, we have identified a set of genes that predict functional progesterone signaling in tissue. These data will facilitate an understanding of the ways in which drugs such as TPA may be utilized for the prevention, and possibly the therapy, of human breast cancer. The online version of this article (doi:10.1186/s12885-016-2355-5) contains supplementary material, which is available to authorized users

Vinorelbine-based salvage therapy in HER2-positive metastatic breast cancer patients progressing during trastuzumab-containing regimens: a retrospective study

Directory of Open Access Journals (Sweden)

Viale Giuseppe

2008-07-01

Full Text Available Abstract Background The vinka-alkaloyd vinorelbine is a potentially valuable treatment in patients with HER2-positive, trastuzumab-resistant advanced breast cancer. We sought to document the clinical activity of vinorelbine-based salvage treatments in this clinical setting. Methods We analyzed a cohort of 424 consecutive women receiving trastuzumab-based therapy for HER2-positive advanced breast cancer. Of these, 299 were identified as progressing during the initial trastuzumab-based treatment, and 77 received vinorelbine-based therapy as first salvage treatment. Central review of pathological specimens revealed that 70 patients had HER2-amplification detected by FISH. For these patients we determined overall response rate (ORR = complete-CR + partial-PR and clinical benefit (CB = CR+PR+ Stable disease lasting at least 6 months, time to progression (TTP and overall survival (OS from the initiation of vinorelbine-based salvage therapy. Results In 60 patients who were evaluable for tumor response, ORR and CB rates were 28% (95% C.I. 18%-41% and 50% (95% C.I. 38%-62%, respectively. Median follow-up from the initiation of salvage therapy was 15 months (range 1–63 months. Median TTP and OS were 7.1 months (95% C.I. 6.6–7.7 months and 21 months (95% C.I. 14.3–27.7 months, respectively. No differences in clinical outcomes were observed according to whether vinorelbine was administered as a single agent or in combination with other cytostatics, or whether trastuzumab was stopped or continued beyond disease progression. Conclusion our findings suggests that vinorelbine-based combinations are active and should be further evaluated in studies conducted in trastuzumab-resistant patients, including those evaluating newer HER2-targeting agents.

Breast cancer pulmonary metastasis is increased in mice undertaking spontaneous physical training in the running wheel; a call for revising beneficial effects of exercise on cancer progression.

Science.gov (United States)

Smeda, Marta; Przyborowski, Kamil; Proniewski, Bartosz; Zakrzewska, Agnieszka; Kaczor, Dawid; Stojak, Marta; Buczek, Elzbieta; Nieckarz, Zenon; Zoladz, Jerzy A; Wietrzyk, Joanna; Chlopicki, Stefan

2017-01-01

It has been repeatedly shown that regular aerobic exercise exerts beneficial effects on incidence and progression of cancer. However, the data regarding effects of exercise on metastatic dissemination remain conflicting. Therefore, in the present study the possible preventive effects of voluntary wheel running on primary tumor growth and metastases formation in the model of spontaneous pulmonary metastasis were analyzed after orthotopic injection of 4T1 breast cancer cells into mammary fat pads of female Balb/C mice. This study identified that in the mice injected with 4T1 breast cancer cells and running on the wheels (4T1 ex) the volume and size of the primary tumor were not affected, but the number of secondary nodules formed in the lungs was significantly increased compared to their sedentary counterparts (4T1 sed). This effect was associated with decreased NO production in the isolated aorta of exercising mice (4T1 ex), suggesting deterioration of endothelial function that was associated with lower platelet count without their overactivation. This was evidenced by comparable selectin P, active GPIIb/IIIa expression, fibrinogen and vWF binding on the platelet surface. In conclusion, voluntary wheel running appeared to impair, rather than improve endothelial function, and to promote, but not decrease metastasis in the murine orthotopic model of metastatic breast cancer. These results call for revising the notion of the persistent beneficial effects of voluntary exercise on breast cancer progression, though further studies are needed to elucidate mechanisms involved in pro-metastatic effects of voluntary exercise.

Technical progress report

International Nuclear Information System (INIS)

1996-01-01

This report summarizes experimental and theoretical work in basic nuclear physics carried out between October 1, 1995, the closing of our last Progress Report, and September 30, 1996 at the Nuclear Physics Laboratory of the University of Colorado, Boulder, under contracts DE-FG03-93ER-40774 and DE-FG03-95ER-40913 with the United States Department of Energy. The experimental contract supports broadly-based experimental research in intermediate energy nuclear physics. This report includes results from studies of Elementary Systems involving the study of the structure of the nucleon via polarized high-energy positron scattering (the HERMES experiment) and lower energy pion scattering from both polarized and unpolarized nucleon targets. Results from pion- and kaon-induced reactions in a variety of nuclear systems are reported under the section heading Meson Reactions; the impact of these and other results on understanding the nucleus is presented in the Nuclear Structure section. In addition, new results from scattering of high-energy electrons (from CEBAF/TJNAF) and pions (from KEK) from a broad range of nuclei are reported in the section on Incoherent Reactions. Finally, the development and performance of detectors produced by the laboratory are described in the section titled Instrumentation

Update in breast MRT. Standards and quality management; Update in der Mamma-MRT-Technik. Untersuchungsstandards und Qualitaetssicherung

Energy Technology Data Exchange (ETDEWEB)

Kurtz, Claudia [Kantonsspital Luzern, Lucerne (Switzerland). Inst. fuer Radiologie

2013-06-15

Meanwhile breast MRI has emerged to an important tool for breast diagnostics, with a broad spectrum of technical requirements and interpretation guidelines. The use of breast MRI is reasonable and helpful, provided that an appropriate application and optimal technical conditions are fulfilled, otherwise unnecessary follow-up examinations or biopsies might be initiated. This article gives an overview about planning and performing the examination, describes the physical background for optimal acquisition protocols, gives support for post-processing and image interpretation and also refers to possible misinterpretations. (orig.)

Development of a Combination Cell and Gene Therapy Approach for Early-Stage Breast Cancer

National Research Council Canada - National Science Library

Lewis, Michael T

2005-01-01

The unique biology of the breast presents the opportunity to these cell and gene therapy techniques in a way that circumvents many of these technical limitations for the treatment of early stage breast cancer...

Program for Critical Technologies in Breast Oncology

National Research Council Canada - National Science Library

Costa, Jose

1997-01-01

In Year 3 of The Program for Critical Technologies in Breast Oncology (PCTBO), we have expanded services that were initiated in July 1994 to establish a core technical and tissue procurement resource that: (1...

Autophagy in breast cancer and its implications for therapy

Science.gov (United States)

Jain, Kirti; Paranandi, Krishna S; Sridharan, Savitha; Basu, Alakananda

2013-01-01

Autophagy is an evolutionarily conserved process of cellular self-digestion that serves as a mechanism to clear damaged organelles and recycle nutrients. Since autophagy can promote cell survival as well as cell death, it has been linked to different human pathologies, including cancer. Although mono-allelic deletion of autophagy-related gene BECN1 in breast tumors originally indicated a tumor suppressive role for autophagy in breast cancer, the intense research during the last decade suggests a role for autophagy in tumor progression. It is now recognized that tumor cells often utilize autophagy to survive various stresses, such as oncogene-induced transformation, hypoxia, endoplasmic reticulum (ER) stress and extracellular matrix detachment. Induction of autophagy by tumor cells may also contribute to tumor dormancy and resistance to anticancer therapies, thus making autophagy inhibitors promising drug candidates for breast cancer treatment. The scientific endeavors continue to define a precise role for autophagy in breast cancer. In this article, we review the current literature on the role of autophagy during the development and progression of breast cancer, and discuss the potential of autophagy modulators for breast cancer treatment. PMID:23841025

A systematic assessment of the state of hazardous waste clean-up technologies. Quarterly technical progress report, April 1--June 30, 1993

Energy Technology Data Exchange (ETDEWEB)

Berg, M.T.; Reed, B.E.; Gabr, M.

1993-07-01

West Virginia University (WVU) and the US DOE Morgantown Energy Technology Center (METC) entered into a Cooperative Agreement on August 29, 1992 entitled ``Decontamination Systems Information and Research Programs.`` Stipulated within the Agreement is the requirement that WVU submit to METC a series of Technical Progress Report for Year 1 of the Agreement. This report reflects the progress and/or efforts performed on the following nine technical projects encompassed by the Year 1 Agreement for the period of April 1 through June 30, 1993: Systematic assessment of the state of hazardous waste clean-up technologies; site remediation technologies -- drain-enhanced soil flushing (DESF) for organic contaminants removal; site remediation technologies -- in situ bioremediation of organic contaminants; excavation systems for hazardous waste sites; chemical destruction of polychlorinated biphenyls; development of organic sensors -- monolayer and multilayer self-assembled films for chemical sensors; Winfield lock and dam remediation; Assessments of Technologies for hazardous waste site remediation -- non-treatment technologies and pilot scale test facility implementation; and remediation of hazardous sites with stream reforming.

Does depression decrease the moderating effect of self-efficacy in the relationship between illness perception and fear of progression in breast cancer?

Science.gov (United States)

Shim, Eun-Jung; Lee, Jong Won; Min, Yul Ha

2018-02-01

Fear of progression (FOP) is a prevalent concern among breast cancer patients that affect their adjustment to disease. This study examined whether self-efficacy moderates the effect of illness perception (IP) on FOP and whether the moderating effect of self-efficacy depends on the level of depressive symptoms. A cross-sectional survey including brief illness perception questionnaire (BIPQ), FOP short form, general self-efficacy scale, and the center for epidemiologic studies depression scale were administered to 245 patients with breast cancer in Korea. Self-efficacy moderated the negative impact of the patients' perception of chronic timeline and a greater emotional impact of the illness on FOP. However, the moderating effect of self-efficacy of the BIPQ timeline and emotions on FOP depended on level of depressive symptoms. The findings underscore the importance of considering the IP as determinants of FOP, as well as of self-efficacy and depression as the moderating factors in the relationship between IP and FOP, suggesting the need to enhance self-efficacy and depressive symptoms in order to compensate the negative impact of IP on FOP in breast cancer patients. Copyright © 2017 John Wiley & Sons, Ltd.

IMMUNOPHENOTYPIC CHARACTERISTICS OF INFLAMMATORY BREAST CANCER

Directory of Open Access Journals (Sweden)

A. I. Berishvili

2009-01-01

Full Text Available The investigation enrolled 31 patients with inflammatory breast cancer (IBC treated at the N. N. Blokhin Cancer Research Center from 2006 to 2008. IBC is diagnosed on the basis of signs of rapid progression, such as localized or generalized breast induration, red- ness and edema. IBC accounts for less than 5% of all diagnosed breast cancers and is the most lethal form of primary breast cancer. We studied tumor markers of the immunophenotype of IBC and levels and subpopulations of immunocompetent tumor-infiltrating cells. We found that expression of HLA-DR is in negative correlation with MUC-1 expression and lymphoid cells tumor infiltration is asso- ciated with the increase in T-cell subpopulations.

Transforming growth factor-β1 promotes breast cancer metastasis by downregulating miR-196a-3p expression.

Science.gov (United States)

Chen, Yan; Huang, Shai; Wu, Bo; Fang, Jiankai; Zhu, Minsheng; Sun, Li; Zhang, Lifeng; Zhang, Yongsheng; Sun, Maomin; Guo, Lingling; Wang, Shouli

2017-07-25

Transforming growth factor-β1 is considered a key contributor to the progression of breast cancer. MicroRNAs are important factors in the development and progression of many malignancies. In the present study, upon studies of breast cancer cell lines and tissues, we showed that microRNA -196a-3p is decreased by transforming growth factor-β1 in breast cancer cells and associated with breast cancer progression. We identified neuropilin-2 as a target gene of microRNA -196a-3p and showed that it is regulated by transforming growth factor-β1. Moreover, transforming growth factor-β1-mediated inhibition of microRNA -196a-3p and activation of neuropilin-2were required for transforming growth factor-β1-induced migration and invasion of breast cancer cells. In addition, neuropilin-2 expression was suppressed in breast tumors, particularly in triple-negative breast cancers. Collectively, our findings strongly indicate that microRNA -196a-3p is a predictive biomarker of breast cancer metastasis and patient survival and a potential therapeutic target in metastatic breast cancer.

Genome evolution during progression to breast cancer

KAUST Repository

Newburger, D. E.; Kashef-Haghighi, D.; Weng, Z.; Salari, R.; Sweeney, R. T.; Brunner, A. L.; Zhu, S. X.; Guo, X.; Varma, S.; Troxell, M. L.; West, R. B.; Batzoglou, S.; Sidow, A.

2013-01-01

Cancer evolution involves cycles of genomic damage, epigenetic deregulation, and increased cellular proliferation that eventually culminate in the carcinoma phenotype. Early neoplasias, which are often found concurrently with carcinomas and are histologically distinguishable from normal breast tissue, are less advanced in phenotype than carcinomas and are thought to represent precursor stages. To elucidate their role in cancer evolution we performed comparative whole-genome sequencing of early neoplasias, matched normal tissue, and carcinomas from six patients, for a total of 31 samples. By using somatic mutations as lineage markers we built trees that relate the tissue samples within each patient. On the basis of these lineage trees we inferred the order, timing, and rates of genomic events. In four out of six cases, an early neoplasia and the carcinoma share a mutated common ancestor with recurring aneuploidies, and in all six cases evolution accelerated in the carcinoma lineage. Transition spectra of somatic mutations are stable and consistent across cases, suggesting that accumulation of somatic mutations is a result of increased ancestral cell division rather than specific mutational mechanisms. In contrast to highly advanced tumors that are the focus of much of the current cancer genome sequencing, neither the early neoplasia genomes nor the carcinomas are enriched with potentially functional somatic point mutations. Aneuploidies that occur in common ancestors of neoplastic and tumor cells are the earliest events that affect a large number of genes and may predispose breast tissue to eventual development of invasive carcinoma.

Genome evolution during progression to breast cancer

KAUST Repository

Newburger, D. E.

2013-04-08

Cancer evolution involves cycles of genomic damage, epigenetic deregulation, and increased cellular proliferation that eventually culminate in the carcinoma phenotype. Early neoplasias, which are often found concurrently with carcinomas and are histologically distinguishable from normal breast tissue, are less advanced in phenotype than carcinomas and are thought to represent precursor stages. To elucidate their role in cancer evolution we performed comparative whole-genome sequencing of early neoplasias, matched normal tissue, and carcinomas from six patients, for a total of 31 samples. By using somatic mutations as lineage markers we built trees that relate the tissue samples within each patient. On the basis of these lineage trees we inferred the order, timing, and rates of genomic events. In four out of six cases, an early neoplasia and the carcinoma share a mutated common ancestor with recurring aneuploidies, and in all six cases evolution accelerated in the carcinoma lineage. Transition spectra of somatic mutations are stable and consistent across cases, suggesting that accumulation of somatic mutations is a result of increased ancestral cell division rather than specific mutational mechanisms. In contrast to highly advanced tumors that are the focus of much of the current cancer genome sequencing, neither the early neoplasia genomes nor the carcinomas are enriched with potentially functional somatic point mutations. Aneuploidies that occur in common ancestors of neoplastic and tumor cells are the earliest events that affect a large number of genes and may predispose breast tissue to eventual development of invasive carcinoma.

Putative Biomarkers and Targets of Estrogen Receptor Negative Human Breast Cancer

Directory of Open Access Journals (Sweden)

Stephen W. Byers

2011-07-01

Full Text Available Breast cancer is a progressive and potentially fatal disease that affects women of all ages. Like all progressive diseases, early and reliable diagnosis is the key for successful treatment and annihilation. Biomarkers serve as indicators of pathological, physiological, or pharmacological processes. Her2/neu, CA15.3, estrogen receptor (ER, progesterone receptor (PR, and cytokeratins are biomarkers that have been approved by the Food and Drug Administration for disease diagnosis, prognosis, and therapy selection. The structural and functional complexity of protein biomarkers and the heterogeneity of the breast cancer pathology present challenges to the scientific community. Here we review estrogen receptor-related putative breast cancer biomarkers, including those of putative breast cancer stem cells, a minor population of estrogen receptor negative tumor cells that retain the stem cell property of self renewal. We also review a few promising cytoskeleton targets for ER alpha negative breast cancer.

GT-MHR COMMERCIALZATION STUDY. TECHNICAL PROGRESS AND COST MANAGEMENT REPORT FOR THE PERIOD MAY 1 THROUGH MAY 31, 2003

International Nuclear Information System (INIS)

SHENOY, A.S.

2003-01-01

A271 GT-MHR COMMERCIALZATION STUDY TECHNICAL PROGRESS AND COST MANAGEMENT REPORT FOR THE PERIOD MAY 1 THROUGH MAY 31, 2003. Petten advised GA the start of the HFR-EU2 irradiation is being delayed until late July 2004. HFR-EU1 (pebble fuel) is also delayed until February/March 2004. The reason for the delays was implementation of new financial regulations at Petten that delayed the contracts for capsule fabrication. Review of the MHR-2 Fuel Product Specification was completed. Revision of the specification to incorporate the review results is in progress. Detailed test matrices have been drafted for capsule irradiation tests and for post-irradiation heating tests proposed for development and qualification of advanced coated-particle fuels capable of meeting anticipated VHTR fuel performance requirements

Hierarchical clustering of breast cancer methylomes revealed differentially methylated and expressed breast cancer genes.

Directory of Open Access Journals (Sweden)

I-Hsuan Lin

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

Prognosis of breast cancer is associated with one-carbon metabolism related nutrients among Korean women

Directory of Open Access Journals (Sweden)

Lee Yunhee

2012-08-01

Full Text Available Abstract Background The 5-year survival rate for breast cancer among Korean women has increased steadily; however, breast cancer remains the leading cause of cancer mortality among women. One-carbon metabolism, which requires an adequate supply of methyl group donors and B vitamins, may affect the prognosis of breast cancer. This aim of this study was to investigate the associations of dietary intake of vitamin B2, vitamin B6 and folate before diagnosis on the prognosis of breast cancer. Methods We assessed the dietary intake using a food frequency questionnaire with 980 women who were newly diagnosed and histopathologically confirmed to have primary breast cancer from hospitals in Korea, and 141 disease progression events occurred. Cox’s proportional hazard regression models were used to estimate the hazard ratio (HR and 95% confidence interval (95% CI adjusting for age, education, recruitment sites, TNM stage, hormone status, nuclear grade and total calorie. Results There was no significant association between any one-carbon metabolism related nutrients (vitamin B2, B6 and folate and the progression of breast cancer overall. However, one-carbon metabolism related nutrients were associated with disease progression in breast cancer patients stratified by subtypes. In ER + and/or PR + breast cancers, no association was observed; however, in ER–/PR– breast cancers, a high intake of vitamin B2 and folate statistically elevated the HR of breast cancer progression (HR = 2.28; 95% CI, 1.20-4.35, HR = 1.84; 95% CI, 1.02-3.32, respectively compared to a low intake. This positive association between the ER/PR status and progression of the disease was profound when the nutrient intakes were categorized in a combined score (Pinteraction = 0.018. In ER–/PR– breast cancers, high combined scores were associated with a significantly poor DFS compared to those belonging to the low score group (HR = 3.84; 95% CI, 1

Index to Nuclear Safety. A technical progress review by chronology, permuted title, and author. Vol 11, No. 1 through Vol. 16, No. 6

International Nuclear Information System (INIS)

Cottrell, W.B.; Klein, A.

1976-04-01

This index to Nuclear Safety covers articles in Nuclear Safety Vol. 11, No. 1 (Jan.-Feb. 1970) through Vol. 16, No. 6 (Nov.-Dec. 1975). Included in the index is a chronological list of articles (including abstract) followed by both a KWIC index and an Author Index. Nuclear Safety is a bimonthly technical progress review prepared by the Nuclear Safety Information Center and covers all safety aspects of nuclear power reactors and associated facilities. The index lists over 300 technical articles in the last six years of publication

Index to Nuclear Safety. A technical progress review by chronology, permuted title, and author. Vol 11, No. 1 through Vol. 16, No. 6

Energy Technology Data Exchange (ETDEWEB)

Cottrell, W.B.; Klein, A.

1976-04-01

This index to Nuclear Safety covers articles in Nuclear Safety Vol. 11, No. 1 (Jan.-Feb. 1970) through Vol. 16, No. 6 (Nov.-Dec. 1975). Included in the index is a chronological list of articles (including abstract) followed by both a KWIC index and an Author Index. Nuclear Safety is a bimonthly technical progress review prepared by the Nuclear Safety Information Center and covers all safety aspects of nuclear power reactors and associated facilities. The index lists over 300 technical articles in the last six years of publication.

Melatonin, Aging and Breast Cancer

National Research Council Canada - National Science Library

Hill, Steven

2001-01-01

... conditions for tumor induction, promotion and progression. The pineal gland, via its hormone melatonin, has been shown by numerous laboratories to inhibit the proliferation of both human and animal models of breast cancer...

Necrotizing fasciitis of breast | Salati | East and Central African ...

African Journals Online (AJOL)

Necrotizing fasciitis is an uncommon and rapidly progressive, life-threatening soft tissue infection. Necrotizing fasciitis of breast is even rarely encountered. We managed one such 32 years old nondiabetic, obese lady who developed necrotising fascitis of right breast after lumpectomy. Management involved wide ...

Urology technical and non-technical skills development: the emerging role of simulation.

Science.gov (United States)

Rashid, Prem; Gianduzzo, Troy R J

2016-04-01

To review the emerging role of technical and non-technical simulation in urological education and training. A review was conducted to examine the current role of simulation in urology training. A PUBMED search of the terms 'urology training', 'urology simulation' and 'urology education' revealed 11,504 titles. Three hundred and fifty-seven abstracts were identified as English language, peer reviewed papers pertaining to the role of simulation in urology and related topics. Key papers were used to explore themes. Some cross-referenced papers were also included. There is an ongoing need to ensure that training time is efficiently utilised while ensuring that optimal technical and non-technical skills are achieved. Changing working conditions and the need to minimise patient harm by inadvertent errors must be taken into account. Simulation models for specific technical aspects have been the mainstay of graduated step-wise low and high fidelity training. Whole scenario environments as well as non-technical aspects can be slowly incorporated into the curriculum. Doing so should also help define what have been challenging competencies to teach and evaluate. Dedicated time, resources and trainer up-skilling are important. Concurrent studies are needed to help evaluate the effectiveness of introducing step-wise simulation for technical and non-technical competencies. Simulation based learning remains the best avenue of progressing surgical education. Technical and non-technical simulation could be used in the selection process. There are good economic, logistic and safety reasons to pursue the process of ongoing development of simulation co-curricula. While the role of simulation is assured, its progress will depend on a structured program that takes advantage of what can be delivered via this medium. Overall, simulation can be developed further for urological training programs to encompass technical and non-technical skill development at all stages, including

Power systems development facility. Quarterly technical progress report, January 1, 1994--March 31, 1994

Energy Technology Data Exchange (ETDEWEB)

1994-07-01

This quarterly technical progress report summarizes work completed during the last quarter of the Second Budget Period, January 1 through March 31, 1994, entitled {open_quotes}Hot Gas Cleanup Test Facility for Gasification and Pressurized Combustion.{close_quotes} The objective of this project is to evaluate hot gas particulate control technologies using coal-derived gas streams. This will entail the design, construction, installation, and use of a flexible test facility which can operate under realistic gasification and combustion conditions. The major particulate control device issues to be addressed include the integration of the particulate control devices into coal utilization systems, on-line cleaning techniques, chemical and thermal degradation of components, fatigue or structural failures, blinding, collection efficiency as a function of particle size, and scale-up of particulate control systems to commercial size.

Understanding breast cancer - The long and winding road.

Science.gov (United States)

Lukong, Kiven Erique

2017-06-01

Despite a remarkable increase in the depth of our understanding and management of breast cancer in the past 50 years, the disease is still a major public health problem worldwide and poses significant challenges. The palpability of breast tumors has facilitated diagnosis and documentation since ancient times. The earliest descriptions of breast cancer date back to around 3500 BCE. For centuries to follow, theories by Hippocrates (460 BCE) and Galen (200 CE), attributing the cause of breast cancer to an "excess of black bile" and treatment options including the use of opium and castor oil, prevailed. Surgical resection was introduced in the 18th century. The advent of modern medicine led to the development of novel treatment options that include hormonal, targeted and chemo-therapies. There are still several therapeutic challenges including the treatment of triple negative breast cancer (TNBC), and overcoming drug resistance. The increased incidence and awareness of breast cancer has led to significant changes in diagnosis and treatment in recent decades. But, mankind has come a long way. Herein, I have traced how our understanding of breast cancer has evolved from the early description of the disease around 460 BCE as "black bile-containing crab-like tumors" to the conventional as a heterogeneous disease with high degree of diversity between and within tumors, as well as among breast cancer patients. How is breast cancer treated today and how do risk factors, breast cancer subtype and drug resistance contribute to the therapeutic challenges at the turn of the 21st century? Breast cancer remains a serious public health issue worldwide. However, appreciable growth in our understanding of breast cancer in the past century has led to remarkable progress in the early detection, treatment and prevention of the disease. The clinical focus is shifting more towards tailored therapy as more targets are characterized and novel highly innovative approaches are developed

Insulin-Like Growth Factor-1 Inscribes a Gene Expression Profile for Angiogenic Factors and Cancer Progression in Breast Epithelial Cells

Directory of Open Access Journals (Sweden)

J.S. Oh

2002-01-01

Full Text Available Activation of the insulin-like growth factor-1 receptor (IGF-11R by IGF-1 is associated with the risk and progression of many types of cancer, although despite this it remains unclear how activated IGF-1 R contributes to cancer progression. In this study, gene expression changes elicited by IGF-1 were profiled in breast epithelial cells. We noted that many genes are functionally linked to cancer progression and angiogenesis. To validate some of the changes observed, the RNA and/or protein was confirmed for c-fos, cytochrome P4501Al, cytochrome P450 1131, interleukin-1 beta, fas ligand, vascular endothelial growth factor, and urokinase plasminogen activator. Nuclear proteins were also temporally monitored to address how gene expression changes were regulated. We found that IGF-1 stimulated the nuclear translocation of phosphorylated AKT, hypoxic-inducible factor-1 alpha, and phosphorylated cAMP-responsive element-binding protein, which correlated with temporal changes in gene expression. Next, the promoter regions of IGF-1-regulated genes were searched in silico. The promoters of genes that clustered together had similar regulatory regions. In summary, IGF-1 inscribes a gene expression profile relevant to cancer progression, and this study provides insight into the mechanism(s whereby some of these changes occur.

Heavy-ion mammography and breast cancer

International Nuclear Information System (INIS)

Fabrikant, J.I.; Tobias, C.A.; Capp, M.P.; Holley, W.R.; Woodruff, K.H.; Sickles, E.A.

1980-01-01

Heavy-ion radiography is a new diagnostic imaging technique developed in our laboratory that produces superior density resolution at low radiation doses. Heavy-ion mammography has now emerged as a low-dose, safe, reliable, noninvasive diagnostic radiological procedure that can quantitate and image very small differences in soft tissue densities in the breast tissues of patients with clinical breast disease. The improved density resolution of heavy-ion mammography over conventional X-ray mammography and breast xerography provides the potential of detecting small breast cancers of less than 1 cm diameter. The radiation dose to the breast from carbon-ion mammorgraphy is about 50 mrad or less, and can potentially be only a fraction of this level. The results of the present clinical trial in progress of heavy-ion mammography in 37 patients, thus far studied, are extremely encouraging, and warrant continued study for application to the early diagnosis of breast cancer in women

Dietary influence on estrogens and cytokines in breast cancer

Directory of Open Access Journals (Sweden)

Xin Nian

2017-07-01

Full Text Available Breast cancer affects one out of eight women in their lifetime. Many factors contribute to the development of breast cancer, such as hereditary mutations and lifetime exposure to environmental factors, including estrogen. In addition, overweight and obesity, especially with increased waist circumference, are known to be associated with breast cancer risk. This review will summarize our understanding of the effect of diet on breast cancer incidence and progression. Since some inflammatory cytokines that are changed by a high-fat diet are known to promote the growth of breast cancer cells, these cytokines may serve as biomarkers to monitor the dietary influence for women at high risk of breast cancer and as future therapeutic targets for breast cancer treatment.

Podoplanin increases the migration of human fibroblasts and affects the endothelial cell network formation: A possible role for cancer-associated fibroblasts in breast cancer progression.

Directory of Open Access Journals (Sweden)

Jaroslaw Suchanski

Full Text Available In our previous studies we showed that in breast cancer podoplanin-positive cancer-associated fibroblasts correlated positively with tumor size, grade of malignancy, lymph node metastasis, lymphovascular invasion and poor patients' outcome. Therefore, the present study was undertaken to assess if podoplanin expressed by fibroblasts can affect malignancy-associated properties of breast cancer cells. Human fibroblastic cell lines (MSU1.1 and Hs 578Bst overexpressing podoplanin and control fibroblasts were co-cultured with breast cancer MDA-MB-231 and MCF7 cells and the impact of podoplanin expressed by fibroblasts on migration and invasiveness of breast cancer cells were studied in vitro. Migratory and invasive properties of breast cancer cells were not affected by the presence of podoplanin on the surface of fibroblasts. However, ectopic expression of podoplanin highly increases the migration of MSU1.1 and Hs 578Bst fibroblasts. The present study also revealed for the first time, that podoplanin expression affects the formation of pseudo tubes by endothelial cells. When human HSkMEC cells were co-cultured with podoplanin-rich fibroblasts the endothelial cell capillary-like network was characterized by significantly lower numbers of nodes and meshes than in co-cultures of endothelial cells with podoplanin-negative fibroblasts. The question remains as to how our experimental data can be correlated with previous clinical data showing an association between the presence of podoplanin-positive cancer-associated fibroblasts and progression of breast cancer. Therefore, we propose that expression of podoplanin by fibroblasts facilitates their movement into the tumor stroma, which creates a favorable microenvironment for tumor progression by increasing the number of cancer-associated fibroblasts, which produce numerous factors affecting proliferation, survival and invasion of cancer cells. In accordance with this, the present study revealed for the first

Podoplanin increases the migration of human fibroblasts and affects the endothelial cell network formation: A possible role for cancer-associated fibroblasts in breast cancer progression.

Science.gov (United States)

Suchanski, Jaroslaw; Tejchman, Anna; Zacharski, Maciej; Piotrowska, Aleksandra; Grzegrzolka, Jedrzej; Chodaczek, Grzegorz; Nowinska, Katarzyna; Rys, Janusz; Dziegiel, Piotr; Kieda, Claudine; Ugorski, Maciej

2017-01-01

In our previous studies we showed that in breast cancer podoplanin-positive cancer-associated fibroblasts correlated positively with tumor size, grade of malignancy, lymph node metastasis, lymphovascular invasion and poor patients' outcome. Therefore, the present study was undertaken to assess if podoplanin expressed by fibroblasts can affect malignancy-associated properties of breast cancer cells. Human fibroblastic cell lines (MSU1.1 and Hs 578Bst) overexpressing podoplanin and control fibroblasts were co-cultured with breast cancer MDA-MB-231 and MCF7 cells and the impact of podoplanin expressed by fibroblasts on migration and invasiveness of breast cancer cells were studied in vitro. Migratory and invasive properties of breast cancer cells were not affected by the presence of podoplanin on the surface of fibroblasts. However, ectopic expression of podoplanin highly increases the migration of MSU1.1 and Hs 578Bst fibroblasts. The present study also revealed for the first time, that podoplanin expression affects the formation of pseudo tubes by endothelial cells. When human HSkMEC cells were co-cultured with podoplanin-rich fibroblasts the endothelial cell capillary-like network was characterized by significantly lower numbers of nodes and meshes than in co-cultures of endothelial cells with podoplanin-negative fibroblasts. The question remains as to how our experimental data can be correlated with previous clinical data showing an association between the presence of podoplanin-positive cancer-associated fibroblasts and progression of breast cancer. Therefore, we propose that expression of podoplanin by fibroblasts facilitates their movement into the tumor stroma, which creates a favorable microenvironment for tumor progression by increasing the number of cancer-associated fibroblasts, which produce numerous factors affecting proliferation, survival and invasion of cancer cells. In accordance with this, the present study revealed for the first time, that such

Experiences with a new breast localisation needle

International Nuclear Information System (INIS)

Hergan, K.; Amann, T.; Doringer, W.; Hollenstein, P.

1990-01-01

In view of the increasing number of biopsies of non-palpable lesions of the female breast we found an ideal localisation system in the Hawkins breast localisation needle. Localisation was successful without technical problems in 31 out of 34 patients. The special advantages of the needle are its stability in position and excellent manoeverability due to the construction of the needle. The very simple handling of the needle is an advantage not only for the radiologist but also for the surgeon. (orig.) [de

A spreadsheet to determine the volume ratio for target and breast in partial breast irradiation

International Nuclear Information System (INIS)

Kron, T.; Willis, D.; Miller, J.; Hubbard, P.; Oliver, M.; Chua, B.

2009-01-01

Full text: The technical feasibility of Partial Breast Irradiation (PBI) using external beam radiotherapy depends on the ratio between the evaluation planning target volume (PTV e val) and the whole breast volume (PBI volume ratio = PVR). We aimed to develop a simple method to determine PVR using measurements performed at the time of the planning CT scan. A PVR calculation tool was developed using a Microsoft Excel spreadsheet to determine the PTV from three orthogonal dimensions of the seroma cavity and a given margin on the CT scans. The breast volume is estimated from the separation and breast height in five equally spaced CT slices. The PTV e val and whole breast volume were determined for 29 patients from two centres using the spreadsheet calculation tool and compared to volumes delineated on computerised treatment planning systems. Both the PTV e val and whole breast volumes were underestimated by approximately 25% using the spreadsheet. The resulting PVRs were 1.05 +/- 0.35 (mean +/- 1 S D) times larger than the ones determined from planning. Estimations of the PVR using the calculation tool were achievable in around 5 minutes at the time of CT scanning and allow a prompt decision on the suitability of the patients for PBI.

Androgen receptor status is highly conserved during tumor progression of breast cancer.

Science.gov (United States)

Grogg, André; Trippel, Mafalda; Pfaltz, Katrin; Lädrach, Claudia; Droeser, Raoul A; Cihoric, Nikola; Salhia, Bodour; Zweifel, Martin; Tapia, Coya

2015-11-09

With the advent of new and more efficient anti-androgen drugs targeting androgen receptor (AR) in breast cancer (BC) is becoming an increasingly important area of investigation. This would potentially be most useful in triple negative BC (TNBC), where better therapies are still needed. The assessment of AR status is generally performed on the primary tumor even if the tumor has already metastasized. Very little is known regarding discrepancies of AR status during tumor progression. To determine the prevalence of AR positivity, with emphasis on TNBCs, and to investigate AR status during tumor progression, we evaluated a large series of primary BCs and matching metastases and recurrences. AR status was performed on 356 primary BCs, 135 matching metastases, and 12 recurrences using a next-generation Tissue Microarray (ngTMA). A commercially available AR antibody was used to determine AR-status by immunohistochemistry. AR positivity was defined as any nuclear staining in tumor cells ≥1 %. AR expression was correlated with pathological tumor features of the primary tumor. Additionally, the concordance rate of AR expression between the different tumor sites was determined. AR status was positive in: 87 % (307/353) of primary tumors, 86.1 % (105/122) of metastases, and in 66.7 % (8/12) of recurrences. TNBC tested positive in 11.4 %, (4/35) of BCs. A discrepant result was seen in 4.3 % (5/117) of primary BC and matching lymph node (LN) metastases. Three AR negative primary BCs were positive in the matching LN metastasis, representing 17.6 % of all negative BCs with lymph node metastases (3/17). Two AR positive primary BCs were negative in the matching LN metastasis, representing 2.0 % of all AR positive BCs with LN metastases (2/100). No discrepancies were seen between primary BC and distant metastases or recurrence (n = 17). Most primary (87 %) and metastasized (86.1 %) BCs are AR positive including a significant fraction of TNBCs (11.4 %). Further, AR status is

Androgen receptor status is highly conserved during tumor progression of breast cancer

International Nuclear Information System (INIS)

Grogg, André; Trippel, Mafalda; Pfaltz, Katrin; Lädrach, Claudia; Droeser, Raoul A.; Cihoric, Nikola; Salhia, Bodour; Zweifel, Martin; Tapia, Coya

2015-01-01

With the advent of new and more efficient anti-androgen drugs targeting androgen receptor (AR) in breast cancer (BC) is becoming an increasingly important area of investigation. This would potentially be most useful in triple negative BC (TNBC), where better therapies are still needed. The assessment of AR status is generally performed on the primary tumor even if the tumor has already metastasized. Very little is known regarding discrepancies of AR status during tumor progression. To determine the prevalence of AR positivity, with emphasis on TNBCs, and to investigate AR status during tumor progression, we evaluated a large series of primary BCs and matching metastases and recurrences. AR status was performed on 356 primary BCs, 135 matching metastases, and 12 recurrences using a next-generation Tissue Microarray (ngTMA). A commercially available AR antibody was used to determine AR-status by immunohistochemistry. AR positivity was defined as any nuclear staining in tumor cells ≥1 %. AR expression was correlated with pathological tumor features of the primary tumor. Additionally, the concordance rate of AR expression between the different tumor sites was determined. AR status was positive in: 87 % (307/353) of primary tumors, 86.1 % (105/122) of metastases, and in 66.7 % (8/12) of recurrences. TNBC tested positive in 11.4 %, (4/35) of BCs. A discrepant result was seen in 4.3 % (5/117) of primary BC and matching lymph node (LN) metastases. Three AR negative primary BCs were positive in the matching LN metastasis, representing 17.6 % of all negative BCs with lymph node metastases (3/17). Two AR positive primary BCs were negative in the matching LN metastasis, representing 2.0 % of all AR positive BCs with LN metastases (2/100). No discrepancies were seen between primary BC and distant metastases or recurrence (n = 17). Most primary (87 %) and metastasized (86.1 %) BCs are AR positive including a significant fraction of TNBCs (11.4 %). Further, AR status is highly

Infrared absorption of human breast tissues in vitro

Energy Technology Data Exchange (ETDEWEB)

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

2006-07-15

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

Development of a phantom to test fully automated breast density software – A work in progress

International Nuclear Information System (INIS)

Waade, G.G.; Hofvind, S.; Thompson, J.D.; Highnam, R.; Hogg, P.

2017-01-01

Objectives: Mammographic density (MD) is an independent risk factor for breast cancer and may have a future role for stratified screening. Automated software can estimate MD but the relationship between breast thickness reduction and MD is not fully understood. Our aim is to develop a deformable breast phantom to assess automated density software and the impact of breast thickness reduction on MD. Methods: Several different configurations of poly vinyl alcohol (PVAL) phantoms were created. Three methods were used to estimate their density. Raw image data of mammographic images were processed using Volpara to estimate volumetric breast density (VBD%); Hounsfield units (HU) were measured on CT images; and physical density (g/cm 3 ) was calculated using a formula involving mass and volume. Phantom volume versus contact area and phantom volume versus phantom thickness was compared to values of real breasts. Results: Volpara recognized all deformable phantoms as female breasts. However, reducing the phantom thickness caused a change in phantom density and the phantoms were not able to tolerate same level of compression and thickness reduction experienced by female breasts during mammography. Conclusion: Our results are promising as all phantoms resulted in valid data for automated breast density measurement. Further work should be conducted on PVAL and other materials to produce deformable phantoms that mimic female breast structure and density with the ability of being compressed to the same level as female breasts. Advances in knowledge: We are the first group to have produced deformable phantoms that are recognized as breasts by Volpara software. - Highlights: • Several phantoms of different configurations were created. • Three methods to assess phantom density were implemented. • All phantoms were identified as breasts by the Volpara software. • Reducing phantom thickness caused a change in phantom density.

Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition

Directory of Open Access Journals (Sweden)

Flores Juana M

2010-07-01

Full Text Available Abstract Background ErbB2-positive breast cancer is characterized by highly aggressive phenotypes and reduced responsiveness to standard therapies. Although specific ErbB2-targeted therapies have been designed, only a small percentage of patients respond to these treatments and most of them eventually relapse. The existence of this population of particularly aggressive and non-responding or relapsing patients urges the search for novel therapies. The purpose of this study was to determine whether cannabinoids might constitute a new therapeutic tool for the treatment of ErbB2-positive breast tumors. We analyzed their antitumor potential in a well established and clinically relevant model of ErbB2-driven metastatic breast cancer: the MMTV-neu mouse. We also analyzed the expression of cannabinoid targets in a series of 87 human breast tumors. Results Our results show that both Δ9-tetrahydrocannabinol, the most abundant and potent cannabinoid in marijuana, and JWH-133, a non-psychotropic CB2 receptor-selective agonist, reduce tumor growth, tumor number, and the amount/severity of lung metastases in MMTV-neu mice. Histological analyses of the tumors revealed that cannabinoids inhibit cancer cell proliferation, induce cancer cell apoptosis, and impair tumor angiogenesis. Cannabinoid antitumoral action relies, at least partially, on the inhibition of the pro-tumorigenic Akt pathway. We also found that 91% of ErbB2-positive tumors express the non-psychotropic cannabinoid receptor CB2. Conclusions Taken together, these results provide a strong preclinical evidence for the use of cannabinoid-based therapies for the management of ErbB2-positive breast cancer.

Oxidative stress specifically downregulates survivin to promote breast tumour formation.

Science.gov (United States)

Pervin, S; Tran, L; Urman, R; Braga, M; Parveen, M; Li, S A; Chaudhuri, G; Singh, R

2013-03-05

Breast cancer, a heterogeneous disease has been broadly classified into oestrogen receptor positive (ER+) or oestrogen receptor negative (ER-) tumour types. Each of these tumours is dependent on specific signalling pathways for their progression. While high levels of survivin, an anti-apoptotic protein, increases aggressive behaviour in ER- breast tumours, oxidative stress (OS) promotes the progression of ER+ breast tumours. Mechanisms and molecular targets by which OS promotes tumourigenesis remain poorly understood. DETA-NONOate, a nitric oxide (NO)-donor induces OS in breast cancer cell lines by early re-localisation and downregulation of cellular survivin. Using in vivo models of HMLE(HRAS) xenografts and E2-induced breast tumours in ACI rats, we demonstrate that high OS downregulates survivin during initiation of tumourigenesis. Overexpression of survivin in HMLE(HRAS) cells led to a significant delay in tumour initiation and tumour volume in nude mice. This inverse relationship between survivin and OS was also observed in ER+ human breast tumours. We also demonstrate an upregulation of NADPH oxidase-1 (NOX1) and its activating protein p67, which are novel markers of OS in E2-induced tumours in ACI rats and as well as in ER+ human breast tumours. Our data, therefore, suggest that downregulation of survivin could be an important early event by which OS initiates breast tumour formation.

48 CFR 742.1170-4 - Progress reporting requirements and contract clause.

Science.gov (United States)

2010-10-01

... progress. (b) Because the cognizant technical officer is the individual most familiar with the contractor's performance, the contractor must submit the progress reports directly to the cognizant technical officer. The cognizant technical officer must review the reports and advise the contracting officer, in writing, of any...

Estrogen receptor (ER)α-regulated lipocalin 2 expression in adipose tissue links obesity with breast cancer progression.

Science.gov (United States)

Drew, Brian G; Hamidi, Habib; Zhou, Zhenqi; Villanueva, Claudio J; Krum, Susan A; Calkin, Anna C; Parks, Brian W; Ribas, Vicent; Kalajian, Nareg Y; Phun, Jennifer; Daraei, Pedram; Christofk, Heather R; Hewitt, Sylvia C; Korach, Kenneth S; Tontonoz, Peter; Lusis, Aldons J; Slamon, Dennis J; Hurvitz, Sara A; Hevener, Andrea L

2015-02-27

Obesity is associated with increased breast cancer (BrCA) incidence. Considering that inactivation of estrogen receptor (ER)α promotes obesity and metabolic dysfunction in women and female mice, understanding the mechanisms and tissue-specific sites of ERα action to combat metabolic-related disease, including BrCA, is of clinical importance. To study the role of ERα in adipose tissue we generated fat-specific ERα knock-out (FERKO) mice. Herein we show that ERα deletion increased adipocyte size, fat pad weight, and tissue expression and circulating levels of the secreted glycoprotein, lipocalin 2 (Lcn2), an adipokine previously associated with BrCA development. Chromatin immunoprecipitation and luciferase reporter studies showed that ERα binds the Lcn2 promoter to repress its expression. Because adipocytes constitute an important cell type of the breast microenvironment, we examined the impact of adipocyte ERα deletion on cancer cell behavior. Conditioned medium from ERα-null adipocytes and medium containing pure Lcn2 increased proliferation and migration of a subset of BrCA cells in culture. The proliferative and promigratory effects of ERα-deficient adipocyte-conditioned medium on BrCA cells was reversed by Lcn2 deletion. BrCA cell responsiveness to exogenous Lcn2 was heightened in cell types where endogenous Lcn2 expression was minimal, but components of the Lcn2 signaling pathway were enriched, i.e. SLC22A17 and 3-hydroxybutyrate dehydrogenase (BDH2). In breast tumor biopsies from women diagnosed with BrCA we found that BDH2 expression was positively associated with adiposity and circulating Lcn2 levels. Collectively these data suggest that reduction of ERα expression in adipose tissue promotes adiposity and is linked with the progression and severity of BrCA via increased adipocyte-specific Lcn2 production and enhanced tumor cell Lcn2 sensitivity. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Checkpoint inhibitors in breast cancer

DEFF Research Database (Denmark)

Polk, Anne; Svane, Inge-Marie; Andersson, Michael

2018-01-01

INTRODUCTION: An increasing number of compounds directed against immune checkpoints are currently under clinical development. In this review we summarize current research in breast cancer. MATERIAL AND METHODS: A computer-based literature search was carried out using PubMed and EMBASE; data...... reported at international meetings and clinicaltrials.gov were included as well. RESULTS: The obtained overall response rate of PD-1/PD-L1 monotherapy varied from 5 to 30% in heavily pretreated triple negative breast cancer (TNBC). The median duration of progression free survival and overall survival were...... and induce long standing anti-tumor immunity in a subgroup of breast cancer patients. However, the identification of predictive biomarkers is crucial for further development of this treatment modality....

Intraoperative radiotherapy in breast cancer: literature review

International Nuclear Information System (INIS)

Alfaro Hidalgo, Sabrina A.

2013-01-01

A literature review was performed on intraoperative radiotherapy of breast cancer. The strength and attractiveness is established of techniques of partial irradiation in the treatment of breast cancer. The benefit is originated to restrict the area immediate of radiotherapy to the tumor bed or quadrant index and identifying the benefit of being applied during the radiotherapy while surgical lumpectomy. The impact of local recurrence has been established using intraoperative radiotherapy. The advantages of intraoperative radiotherapy was compared in the management of the conservative surgery in early stages of breast cancer with external radiotherapy. Different methods of intraoperative radiotherapy have been compared and individual impact on local recurrence ranges. Intraoperative radiotherapy has had many advantages: radiobiological, technical, clinical, psychological and economical in the handling of conservative surgery in early stages of breast cancer, compared with external radiotherapy [es

Dietary Natural Products for Prevention and Treatment of Breast Cancer

OpenAIRE

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

2017-01-01

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...

Retrospective study of the effect of disease progression on patient reported outcomes in HER-2 negative metastatic breast cancer patients

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Yu Elaine

2011-06-01

Full Text Available Abstract Background This retrospective study evaluated the impact of disease progression and of specific sites of metastasis on patient reported outcomes (PROs that assess symptom burden and health related quality of life (HRQoL in women with metastatic breast cancer (mBC. Methods HER-2 negative mBC patients (n = 102 were enrolled from 7 U.S. community oncology practices. Demographic, disease and treatment characteristics were abstracted from electronic medical records and linked to archived Patient Care Monitor (PCM assessments. The PCM is a self-report measure of symptom burden and HRQoL administered as part of routine care in participating practices. Linear mixed models were used to examine change in PCM scores over time. Results Mean age was 57 years, with 72% of patients Caucasian, and 25% African American. Median time from mBC diagnosis to first disease progression was 8.8 months. Metastasis to bone (60%, lung (28% and liver (26% predominated at initial metastatic diagnosis. Results showed that PCM items assessing fatigue, physical pain and trouble sleeping were sensitive to either general effects of disease progression or to effects associated with specific sites of metastasis. Progression of disease was also associated with modest but significant worsening of General Physical Symptoms, Treatment Side Effects, Acute Distress and Impaired Performance index scores. In addition, there were marked detrimental effects of liver metastasis on Treatment Side Effects, and of brain metastasis on Acute Distress. Conclusions Disease progression has a detrimental impact on cancer-related symptoms. Delaying disease progression may have a positive impact on patients' HRQoL.

Visualization of female breast in bone scintigraphy

International Nuclear Information System (INIS)

Uno, Kimiichi; Uchida, Yoshitaka; Sakata, Shouichi

1992-01-01

Breast cancer incidence rates in Japan has more than doubled in the decade between 1975 and 1985 due to a well-established and affluent Western life-style. One hundred patients having breast cancer, 107 patients having mastectomies, and 243 patients having no breast cancer were reviewed for whole body and spot views of bone scintigraphy with 99m Tc-MDP. The frequency of positive breast uptake in patients with no breast cancer showed a maximum in those patients between the ages of 30 and 40, with a progressive rise and fall before and after the peak, respectively. Patients between the ages of 50 and 60 with breast cancer showed a maximum uptake of 83%, while those patients between the ages of 70 and 80 with breast cancer showed an uptake higher than 50%. There was a markedly higher breast uptake ratio in the breast cancer group compared to the breast cancer free group. Although this scanning agent was of no value in recognition of tumor localization from breast uptake, we have to suspect a high incidence of cancer existence whenever there was unilateral increased breast activity. Even though the mechanism of 99m Tc-MDP uptake by breast tissue is unknown, breast concentration of 99m Tc-MDP appears to be influenced by hormones, especially estrogen. (author)

Palbociclib for Advanced Breast Cancer

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An interim analysis of the PALOMA3 trial shows that women with hormone receptor-positive metastatic breast cancer who received palbociclib plus fulvestrant had longer progression-free survival rates than women who received a placebo plus fulvestrant.

Nuclear structure theory. Annual technical progress report, July 1, 1975--September 30, 1976

International Nuclear Information System (INIS)

French, J.B.; Koltun, D.S.

1976-01-01

This report summarizes progress during the past year in the following areas of nuclear structure and reaction theory: Meson interactions with nucleons and nuclei, including elastic and inelastic scattering of pions, three-body theories of scattering and absorption of pions by deuterons, π-p bremsstrahlung, and multiple-excitation models for meson absorption by heavier nuclei. Studies of the inverse scattering problem including 1 S 0 nucleon-nucleon scattering; the relativistic two-body problem, particularly for relativistic effects at low energies: the unitary-pole expansion in nucleon-nucleon scattering with hard-core interactions. Statistical spectroscopy including: strength distributions and sum rules(both energy weighted and inverse energy weighted) for nuclear excitations; fluctuations and correlations in spectra, strengths and expectation values; studies of Garvey-Kelson and similar mass relationships; spectroscopy in huge spaces including spectral methods for renormalization of the interaction and for using (two + three)-body Skyrme interactions; technical aspects of operator averaging

Polymorphisms in estrogen-metabolizing and estrogen receptor genes and the risk of developing breast cancer among a cohort of women with benign breast disease

International Nuclear Information System (INIS)

Gallicchio, Lisa; Berndt, Sonja I; McSorley, Meghan A; Newschaffer, Craig J; Thuita, Lucy W; Argani, Pedram; Hoffman, Sandra C; Helzlsouer, Kathy J

2006-01-01

A cohort study was conducted to examine the role of genetic polymorphisms in three estrogen metabolizing enzymes (COMT, CYP1A1, CYP1B1) and the two estrogen receptors (ESR1, ESR2) in the progression of benign breast disease (BBD) to breast cancer. Among participants in an ongoing cohort study, 1438 Caucasian women had a breast biopsy for BBD and were successfully genotyped for at least one of the polymorphisms examined in this study. Genotypes were determined using DNA extracted from blood specimens collected in 1989. Incident cases of breast cancer occurring subsequent to BBD diagnosis up to 2003 were identified through cancer registries. Among all participants, the ESR2 *5772G allele was associated with a significant decrease in the risk of breast cancer among women with BBD (Odds Ratio (OR) 0.38; 95% Confidence Interval (CI) 0.15, 0.96). Compared to the reference wild-type genotypes, marginally significant associations with the development of breast cancer were observed between carriers of the variant ESR1 – 104062T allele (OR 0.70, 95% CI 0.45, 1.09), the variant ESR2 *38A allele (OR 1.40; 95% CI 0.88, 2.25), and the variant CYP1B1 453Ser allele (OR 1.48, 95% CI 0.95, 2.32). The results indicate that specific polymorphisms in the CYP1B1, ESR1, and ESR2 genes may play a role in progression of BBD to breast cancer among Caucasian women. Although additional studies are needed to confirm or refute our findings, these results suggest that genetic markers may aid in the identification of women who are at risk for progression of BBD to cancer

Technical aspects of contrast-enhanced magnetic resonance imaging of the breast: literature review

International Nuclear Information System (INIS)

Leopoldino, Denise de Deus; Gracio, Tatiana Schiller; D'Ippolito, Giuseppe; Bezerra, Alexandre Sergio de Araujo; Gracio, Tatiana Schiller

2005-01-01

With the advances in surface coil technology and the development of new imaging protocols in addition to the increase of the use of contrast agents, contrast enhanced magnetic resonance imaging (MRI) has emerged as a promising modality for detection, diagnosis and staging of breast cancer. Despite these advances, there are some unresolved issues, including no defined standard technique for contrast-enhanced breast MRI and no standard criteria of interpretation for the evaluation of such studies. In this article, we review the literature and discuss the general requirements and recommendations for contrast agent-enhanced breast MRI, including image interpretation criteria, MR equipment, dedicated radiofrequency coils, use of paramagnetic contrast agents, fat-suppression techniques, planes of acquisition, pulse sequence specifications and artifact sources. (author)

miR-630 targets IGF1R to regulate response to HER-targeting drugs and overall cancer cell progression in HER2 over-expressing breast cancer.

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Corcoran, Claire; Rani, Sweta; Breslin, Susan; Gogarty, Martina; Ghobrial, Irene M; Crown, John; O'Driscoll, Lorraine

2014-03-24

While the treatment of HER2 over-expressing breast cancer with recent HER-targeted drugs has been highly effective for some patients, primary (also known as innate) or acquired resistance limits the success of these drugs. microRNAs have potential as diagnostic, prognostic and predictive biomarkers, as well as replacement therapies. Here we investigated the role of microRNA-630 (miR-630) in breast cancer progression and as a predictive biomarker for response to HER-targeting drugs, ultimately yielding potential as a therapeutic approach to add value to these drugs. We investigated the levels of intra- and extracellular miR-630 in cells and conditioned media from breast cancer cell lines with either innate- or acquired- resistance to HER-targeting lapatinib and neratinib, compared to their corresponding drug sensitive cell lines, using qPCR. To support the role of miR-630 in breast cancer, we examined the clinical relevance of this miRNA in breast cancer tumours versus matched peritumours. Transfection of miR-630 mimics and inhibitors was used to manipulate the expression of miR-630 to assess effects on response to HER-targeting drugs (lapatinib, neratinib and afatinib). Other phenotypic changes associated with cellular aggressiveness were evaluated by motility, invasion and anoikis assays. TargetScan prediction software, qPCR, immunoblotting and ELISAs, were used to assess miR-630's regulation of mRNA, proteins and their phosphorylated forms. We established that introducing miR-630 into cells with innate- or acquired- resistance to HER-drugs significantly restored the efficacy of lapatinib, neratinib and afatinib; through a mechanism which we have determined to, at least partly, involve miR-630's regulation of IGF1R. Conversely, we demonstrated that blocking miR-630 induced resistance/insensitivity to these drugs. Cellular motility, invasion, and anoikis were also observed as significantly altered by miR-630 manipulation, whereby introducing miR-630 into cells

A Physical Mechanism and Global Quantification of Breast Cancer.

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Chong Yu

Full Text Available Initiation and progression of cancer depend on many factors. Those on the genetic level are often considered crucial. To gain insight into the physical mechanisms of breast cancer, we construct a gene regulatory network (GRN which reflects both genetic and environmental aspects of breast cancer. The construction of the GRN is based on available experimental data. Three basins of attraction, representing the normal, premalignant and cancer states respectively, were found on the phenotypic landscape. The progression of breast cancer can be seen as switching transitions between different state basins. We quantified the stabilities and kinetic paths of the three state basins to uncover the biological process of breast cancer formation. The gene expression levels at each state were obtained, which can be tested directly in experiments. Furthermore, by performing global sensitivity analysis on the landscape topography, six key genes (HER2, MDM2, TP53, BRCA1, ATM, CDK2 and four regulations (HER2⊣TP53, CDK2⊣BRCA1, ATM→MDM2, TP53→ATM were identified as being critical for breast cancer. Interestingly, HER2 and MDM2 are the most popular targets for treating breast cancer. BRCA1 and TP53 are the most important oncogene of breast cancer and tumor suppressor gene, respectively. This further validates the feasibility of our model and the reliability of our prediction results. The regulation ATM→MDM2 has been extensive studied on DNA damage but not on breast cancer. We notice the importance of ATM→MDM2 on breast cancer. Previous studies of breast cancer have often focused on individual genes and the anti-cancer drugs are mainly used to target the individual genes. Our results show that the network-based strategy is more effective on treating breast cancer. The landscape approach serves as a new strategy for analyzing breast cancer on both the genetic and epigenetic levels and can help on designing network based medicine for breast cancer.

Giant Bilateral Juvenile Fibroadenoma of the Breast in Prepubescent Girl.

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Khan, Salma; Khan, Momna; Rafique, Sadia

2015-10-01

Juvenile fibroadenoma accounts for 4% of the total fibroadenomas. Giant juvenile fibroadenoma is found in only 0.5% of all fibroadenomas. The authors report a 10-year girl presenting with progressive enlargement of both breasts for one year. Based on clinical findings and Fine Needle Aspiration Cytology (FNAC), a diagnosis of bilateral giant juvenile fibroadenomas of breast was made. She underwent bilateral lumpectomy with breast conservation and made uneventful postoperative recovery.

Correlations of differentially expressed gap junction connexins Cx26, Cx30, Cx32, Cx43 and Cx46 with breast cancer progression and prognosis.

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Ivett Teleki

Full Text Available Connexins and their cell membrane channels contribute to the control of cell proliferation and compartmental functions in breast glands and their deregulation is linked to breast carcinogenesis. Our aim was to correlate connexin expression with tumor progression and prognosis in primary breast cancers.Meta-analysis of connexin isotype expression data of 1809 and 1899 breast cancers from the Affymetrix and Illumina array platforms, respectively, was performed. Expressed connexins were also monitored at the protein level in tissue microarrays of 127 patients equally representing all tumor grades, using immunofluorescence and multilayer, multichannel digital microscopy. Prognostic correlations were plotted in Kaplan-Meier curves and tested using the log-rank test and cox-regression analysis in univariate and multivariate models.The expression of GJA1/Cx43, GJA3/Cx46 and GJB2/Cx26 and, for the first time, GJA6/Cx30 and GJB1/Cx32 was revealed both in normal human mammary glands and breast carcinomas. Within their subfamilies these connexins can form homo- and heterocellular epithelial channels. In cancer, the array datasets cross-validated each other's prognostic results. In line with the significant correlations found at mRNA level, elevated Cx43 protein levels were linked with significantly improved breast cancer outcome, offering Cx43 protein detection as an independent prognostic marker stronger than vascular invasion or necrosis. As a contrary, elevated Cx30 mRNA and protein levels were associated with a reduced disease outcome offering Cx30 protein detection as an independent prognostic marker outperforming mitotic index and necrosis. Elevated versus low Cx43 protein levels allowed the stratification of grade 2 tumors into good and poor relapse free survival subgroups, respectively. Also, elevated versus low Cx30 levels stratified grade 3 patients into poor and good overall survival subgroups, respectively.Differential expression of Cx43 and Cx

Nuclear waste glass melter: an update of technical progress

International Nuclear Information System (INIS)

Brouns, R.A.; Hanson, M.S.

1984-08-01

The direct slurry-fed ceramic-lined melter is currently the reference US process for treating defense and civilian high-level liquid waste. Extensive nonradioactive pilot-scale testing at Pacific Northwest Laboratory (PNL) and Savannah River Laboratory has proven the process, defined operating parameters, and identified successful equipment design concepts. Programs at PNL continue to support several of the planned US vitrification plants through preparation of equipment designs and flowsheet testing. Current emphasis is on remotization of equipment, radioactive verification testing, and resolution of remaining technical issues. Development of this technology, technical status, and planned development activities are discussed. 9 references, 4 figures

48 CFR 2052.211-70 - Preparation of technical reports.

Science.gov (United States)

2010-10-01

....211-70 Preparation of technical reports. As prescribed at 2011.104-70(a), the contracting officer... Reports (JAN 1993) All technical reports required by Section C and all Technical Progress Reports required... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Preparation of technical...

FY13 Annual Progress Report for SECA Core Technology Program

Energy Technology Data Exchange (ETDEWEB)

Stevenson, Jeffry W. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Koeppel, Brian J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2014-01-31

This progress report covers technical work performed during fiscal year 2013 at PNNL under Field Work Proposal (FWP) 40552. The report highlights and documents technical progress in tasks related to advanced cell and stack component materials development and computational design and simulation.

The challenge of the future. Technical progress and ecological perspectives

International Nuclear Information System (INIS)

Jischa, M.F.

1993-01-01

The book introduces readers into the interrelated global problems population dynamics, energy supply, imminent climate catastrophe, environmetal pollution, finite resources and the conflict between the North and South. It encourages probing more deeply into the technical challenges of the future. The author demonstrates why economic and technical issues will soon be outstripped by questions of the environmental, human and social compatibility of new technologies. (orig./UA) [de

Digital information management: a progress report on the National Digital Mammography Archive

Science.gov (United States)

Beckerman, Barbara G.; Schnall, Mitchell D.

2002-05-01

Digital mammography creates very large images, which require new approaches to storage, retrieval, management, and security. The National Digital Mammography Archive (NDMA) project, funded by the National Library of Medicine (NLM), is developing a limited testbed that demonstrates the feasibility of a national breast imaging archive, with access to prior exams; patient information; computer aids for image processing, teaching, and testing tools; and security components to ensure confidentiality of patient information. There will be significant benefits to patients and clinicians in terms of accessible data with which to make a diagnosis and to researchers performing studies on breast cancer. Mammography was chosen for the project, because standards were already available for digital images, report formats, and structures. New standards have been created for communications protocols between devices, front- end portal and archive. NDMA is a distributed computing concept that provides for sharing and access across corporate entities. Privacy, auditing, and patient consent are all integrated into the system. Five sites, Universities of Pennsylvania, Chicago, North Carolina and Toronto, and BWXT Y12, are connected through high-speed networks to demonstrate functionality. We will review progress, including technical challenges, innovative research and development activities, standards and protocols being implemented, and potential benefits to healthcare systems.

Cordylobia rodhaini infestation of the breast: Report of a case mimicking a breast abscess.

Science.gov (United States)

Grassi, Veronica; Butterworth, James William; Latiffi, Layloma

2016-01-01

Myiasis, parasitic infestation of the body by fly larvae, caused by the Cordylobia rodhaini is very rare with only fourteen cases published since 1970. We present a rare case of myiasis mimicking a breast abscess. A 17-year-old female presented with a nodular ulcerative lesion in her left breast 14days following a trip to Ghana. She had been initially unsuccessfully treated with the antibiotic flucloxacillin following a misdiagnosis of a breast abscess. Following application of Vaseline to the breast wound, covering the wound for 2h and gentle manipulation the larvae was removed successfully and the patient made a good recovery. Presenting as an inflammatory papule with central opening oozing serosanguinous fluid myiasis secondary to C. rodhaini can easily be mistaken for a breast abscess, often avoiding detection by unsuspecting surgeons on initial assessment. In turn ineffective antibiotic treatment is often prescribed leading to further disease progression and associated morbidity. Myiasis secondary to C. rodhaini is a rare but important differential surgeons should consider in women presenting with an inflammatory breast lesion with a recent history of foreign travel to ensure timely diagnosis and treatment. Ultrasound imaging can be useful in confirming diagnosis and avoiding treatment delays. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Role of Estrogen Receptor Signaling in Breast Cancer Metastasis

International Nuclear Information System (INIS)

Roy, S.S.; Vadlamudi, R.K.

2012-01-01

Metastatic breast cancer is a life-threatening stage of cancer and is the leading cause of death in advanced breast cancer patients. Estrogen signaling and the estrogen receptor (ER) are implicated in breast cancer progression, and the majority of the human breast cancers start out as estrogen dependent. Accumulating evidence suggests that ER signaling is complex, involving coregulatory proteins and extranuclear actions. ER-coregualtory proteins are tightly regulated under normal conditions with miss expression primarily reported in cancer. Deregulation of ER coregualtors or ER extranuclear signaling has potential to promote metastasis in ER-positive breast cancer cells. This review summarizes the emerging role of ER signaling in promoting metastasis of breast cancer cells, discusses the molecular mechanisms by which ER signaling contributes to metastasis, and explores possible therapeutic targets to block ER-driven metastasis

Importance of Extracranial Disease Status and Tumor Subtype for Patients Undergoing Radiosurgery for Breast Cancer Brain Metastases

Energy Technology Data Exchange (ETDEWEB)

Dyer, Michael A.; Kelly, Paul J. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Chen, Yu-Hui [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA (United States); Pinnell, Nancy E. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Claus, Elizabeth B. [Harvard Medical School, Boston, MA (United States); Department of Neurosurgery, Brigham and Women' s Hospital, Boston, MA (United States); Yale University School of Medicine, New Haven, CT (United States); Lee, Eudocia Q. [Harvard Medical School, Boston, MA (United States); Center for Neuro-Oncology, Dana-Farber/Brigham and Women' s Center, Boston, MA (United States); Weiss, Stephanie E. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Arvold, Nils D. [Harvard Radiation Oncology Program, Boston, MA (United States); Lin, Nancy U. [Harvard Medical School, Boston, MA (United States); Department of Medical Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Alexander, Brian M., E-mail: bmalexander@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Harvard Medical School, Boston, MA (United States)

2012-07-15

Purpose: In this retrospective study, we report on outcomes and prognostic factors for patients treated with stereotactic radiosurgery (SRS) for breast cancer brain metastases. Methods and Materials: We identified 132 consecutive patients with breast cancer who were treated with SRS for brain metastases from January 2000 through June 2010. We retrospectively reviewed records of the 51 patients with adequate follow-up data who received SRS as part of the initial management of their brain metastases. Overall survival (OS) and time to central nervous system (CNS) progression from the date of SRS were calculated using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. Results: Triple negative subtype was associated with CNS progression on univariate analysis (hazard ratio [HR] = 5.0, p = 0.008). On multivariate analysis, triple negative subtype (HR = 8.6, p = 0.001), Luminal B subtype (HR = 4.3, p = 0.03), and omission of whole-brain radiation therapy (HR = 3.7, p = 0.02) were associated with CNS progression. With respect to OS, Karnofsky Performance Status (KPS) {<=} 80% (HR = 2.0, p = 0.04) and progressive extracranial disease (HR = 3.1, p = 0.002) were significant on univariate analysis; KPS {<=} 80% (HR = 4.1, p = 0.0004), progressive extracranial disease (HR = 6.4, p < 0.0001), and triple negative subtype (HR = 2.9, p = 0.04) were significant on multivariate analysis. Although median survival times were consistent with those predicted by the breast cancer-specific Graded Prognostic Assessment (Breast-GPA) score, the addition of extracranial disease status further separated patient outcomes. Conclusions: Tumor subtype is associated with risk of CNS progression after SRS for breast cancer brain metastases. In addition to tumor subtype and KPS, which are incorporated into the Breast-GPA, progressive extracranial disease may be an important prognostic factor for OS.

Genomic Diversity and the Microenvironment as Drivers of Progression in DCIS

Science.gov (United States)

2015-10-01

progress to invasive breast cancer. We have applied for and received ethical approval to carry out the study at our primary site, and have completed a...cancer, and the application of ecological and other spatial statistics to those images 1-4. 24 Month Milestones: 3 • IHC staining of candidate...Athena Aktipis and Yinyin Yuan: An ecological measure of immune-cancer colocalization as a prognostic factor for breast cancer. Under review at Breast

Overexpression of β1-chain-containing laminins in capillary basement membranes of human breast cancer and its metastases

Science.gov (United States)

Fujita, Manabu; Khazenzon, Natalya M; Bose, Shikha; Sekiguchi, Kiyotoshi; Sasaki, Takako; Carter, William G; Ljubimov, Alexander V; Black, Keith L; Ljubimova, Julia Y

2005-01-01

Introduction Laminins are the major components of vascular and parenchymal basement membranes. We previously documented a switch in the expression of vascular laminins containing the α4 chain from predominantly laminin-9 (α4β2γ1) to predominantly laminin-8 (α4β1γ1) during progression of human brain gliomas to high-grade glioblastoma multiforme. Here, differential expression of laminins was studied in blood vessels and ductal epithelium of the breast. Method In the present study the expressions of laminin isoforms α1–α5, β1–β3, γ1, and γ2 were examined during progression of breast cancer. Forty-five clinical samples of breast tissues including normal breast, ductal carcinomas in situ, invasive ductal carcinomas, and their metastases to the brain were compared using Western blot analysis and immunohistochemistry for various chains of laminin, in particular laminin-8 and laminin-9. Results Laminin α4 chain was observed in vascular basement membranes of most studied tissues, with the highest expression in metastases. At the same time, the expression of laminin β2 chain (a constituent of laminin-9) was mostly seen in normal breast and carcinomas in situ but not in invasive carcinomas or metastases. In contrast, laminin β1 chain (a constituent of laminin-8) was typically found in vessel walls of carcinomas and their metastases but not in those of normal breast. The expression of laminin-8 increased in a progression-dependent manner. A similar change was observed from laminin-11 (α5β2γ1) to laminin-10 (α5β1γ1) during breast tumor progression. Additionally, laminin-2 (α2β1γ1) appeared in vascular basement membranes of invasive carcinomas and metastases. Chains of laminin-5 (α3β3γ2) were expressed in the ductal epithelium basement membranes of the breast and diminished with tumor progression. Conclusion These results suggest that laminin-2, laminin-8, and laminin-10 are important components of tumor microvessels and may associate with breast

Overexpression of β1-chain-containing laminins in capillary basement membranes of human breast cancer and its metastases

International Nuclear Information System (INIS)

Fujita, Manabu; Khazenzon, Natalya M; Bose, Shikha; Sekiguchi, Kiyotoshi; Sasaki, Takako; Carter, William G; Ljubimov, Alexander V; Black, Keith L; Ljubimova, Julia Y

2005-01-01

Laminins are the major components of vascular and parenchymal basement membranes. We previously documented a switch in the expression of vascular laminins containing the α4 chain from predominantly laminin-9 (α4β2γ1) to predominantly laminin-8 (α4β1γ1) during progression of human brain gliomas to high-grade glioblastoma multiforme. Here, differential expression of laminins was studied in blood vessels and ductal epithelium of the breast. In the present study the expressions of laminin isoforms α1–α5, β1–β3, γ1, and γ2 were examined during progression of breast cancer. Forty-five clinical samples of breast tissues including normal breast, ductal carcinomas in situ, invasive ductal carcinomas, and their metastases to the brain were compared using Western blot analysis and immunohistochemistry for various chains of laminin, in particular laminin-8 and laminin-9. Laminin α4 chain was observed in vascular basement membranes of most studied tissues, with the highest expression in metastases. At the same time, the expression of laminin β2 chain (a constituent of laminin-9) was mostly seen in normal breast and carcinomas in situ but not in invasive carcinomas or metastases. In contrast, laminin β1 chain (a constituent of laminin-8) was typically found in vessel walls of carcinomas and their metastases but not in those of normal breast. The expression of laminin-8 increased in a progression-dependent manner. A similar change was observed from laminin-11 (α5β2γ1) to laminin-10 (α5β1γ1) during breast tumor progression. Additionally, laminin-2 (α2β1γ1) appeared in vascular basement membranes of invasive carcinomas and metastases. Chains of laminin-5 (α3β3γ2) were expressed in the ductal epithelium basement membranes of the breast and diminished with tumor progression. These results suggest that laminin-2, laminin-8, and laminin-10 are important components of tumor microvessels and may associate with breast tumor progression. Angiogenic switch

Human breast cancer histoid: an in vitro 3-dimensional co-culture model that mimics breast cancer tissue.

Science.gov (United States)

Kaur, Pavinder; Ward, Brenda; Saha, Baisakhi; Young, Lillian; Groshen, Susan; Techy, Geza; Lu, Yani; Atkinson, Roscoe; Taylor, Clive R; Ingram, Marylou; Imam, S Ashraf

2011-12-01

Progress in our understanding of heterotypic cellular interaction in the tumor microenvironment, which is recognized to play major roles in cancer progression, has been hampered due to unavailability of an appropriate in vitro co-culture model. The aim of this study was to generate an in vitro 3-dimensional human breast cancer model, which consists of cancer cells and fibroblasts. Breast cancer cells (UACC-893) and fibroblasts at various densities were co-cultured in a rotating suspension culture system to establish co-culture parameters. Subsequently, UACC-893, BT.20, or MDA.MB.453 were co-cultured with fibroblasts for 9 days. Co-cultures resulted in the generation of breast cancer histoid (BCH) with cancer cells showing the invasion of fibroblast spheroids, which were visualized by immunohistochemical (IHC) staining of sections (4 µm thick) of BCH. A reproducible quantitative expression of C-erbB.2 was detected in UACC-893 cancer cells in BCH sections by IHC staining and the Automated Cellular Imaging System. BCH sections also consistently exhibited qualitative expression of pancytokeratins, p53, Ki-67, or E-cadherin in cancer cells and that of vimentin or GSTPi in fibroblasts, fibronectin in the basement membrane and collagen IV in the extracellular matrix. The expression of the protein analytes and cellular architecture of BCH were markedly similar to those of breast cancer tissue.

Recent technical developments in radiographic and ultrasonic examinations of the mammary glands

Energy Technology Data Exchange (ETDEWEB)

Friedrich, M

1981-05-01

Apart from the improved film-foil combinations the major innovation in mammography is the scanning technique which enables high-quality mammograms to be made especially of thicker objects of higher density. It has already become the method of choice for screening examinations in the major preventive-care centres for breast cancer. Magnification mammography, on the other hand, has some technical drawbacks and is only used as a supplementary technique of examination. Even though it has not yet reached technical maturity, sonography of the mammary glands already plays an important role as an auxiliary or complementary technique, especially to clear up ambiguous palpatory or mammographic findings. It has only limited value in early detection of breast cancer and should therefore be used only as a supplementary technique.

Association of proteasomal activity with metastasis in luminal breast cancer

Science.gov (United States)

Shashova, E. E.; Fesik, E. A.; Doroshenko, A. V.

2017-09-01

Chimotrypsin-like (ChTL) and caspase-like (CL) proteasomal activities were investigated in different variants of the tumor progression of luminal breast cancer. Patients with primary luminal breast cancer (n = 123) in stage T1-3N0-2M0 who had not received neoadjuvant treatment were included in this study. Proteasome ChTL and CL activities were determined in the samples of tumor and adjacent tissues. The coefficients of chymotrypsin-like (kChTL) and caspase-like (kCL) proteasome activity were also calculated as the ratio of the corresponding activity in the tumor tissue to activity in the adjacent tissue. ChTL, CL, kChTL and kCL in the tissues of luminal A and B breast cancer with lymphogenic metastasis were compared, and their association with hematogenous metastasis was evaluated. On the one hand, CL activity of proteasomes increased in luminal A breast cancer with extensive lymphogenic metastasis (N2), on the other hand it decreased in the luminal B subtype of cancer. The ratio of proteasomal activity in the tumor and adjacent tissues plays a significant role in the hematogenic pathway of breast cancer progression and is associated with poor metastatic-free survival.

Breast imaging and reporting data system (BIRADS): Magnetic resonance imaging

International Nuclear Information System (INIS)

Tardivon, Anne A.; Athanasiou, Alexandra; Thibault, Fabienne; El Khoury, Carl

2007-01-01

This article reviews the technical aspects and interpretation criteria in breast MR imaging based on the first edition of breast imaging and reporting data system (BIRADS) published by the American College of Radiology (ACR) in 2003. In a second article, practical cases will be proposed for training the readers. The major aims of using this lexicon are: first to use a logical and standardized description of MR lesions, secondly to obtain a structured MR report with a clear final impression (BIRADS assessment categories), and thirdly to help comparison between different clinical studies based on similar breast MRI terminology

Technical, Psychological, and Economic Aspects of DIEP Flap Breast Reconstruction

NARCIS (Netherlands)

T.H.C. Damen (Tim)

2011-01-01

textabstractIn the Western world the incidence of breast cancer (BC) is high. In the Netherlands the lifetime risk for women to develop BC is around 13%, making it the most common form of cancer among women with approximately 12.000 women being diagnosed annually. Also, increasing numbers of women

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

Breast-axillary complex in HIV/AIDS patients | Eni | Nigerian Journal ...

African Journals Online (AJOL)

This is a report of three cases seen and managed by the authors. : Three adult female patients presented with progressively increasing axillary and ipsilateral breast swellings. They also had associated fevers and weight loss. Their main concern had been development of breast cancer. One of the patients was a known ...

The Complex Interaction of Matrix Metalloproteinases in the Migration of Cancer Cells through Breast Tissue Stroma

Directory of Open Access Journals (Sweden)

Kerry J. Davies

2014-01-01

Full Text Available Breast cancer mortality is directly linked to metastatic spread. The metastatic cell must exhibit a complex phenotype that includes the capacity to escape from the primary tumour mass, invade the surrounding normal tissue, and penetrate into the circulation before proliferating in the parenchyma of distant organs to produce a metastasis. In the normal breast, cellular structures change cyclically in response to ovarian hormones leading to regulated cell proliferation and apoptosis. Matrix metalloproteinases (MMPs are a family of zinc dependent endopeptidases. Their primary function is degradation of proteins in the extracellular matrix to allow ductal progression through the basement membrane. A complex balance between matrix metalloproteinases and their inhibitors regulate these changes. These proteinases interact with cytokines, growth factors, and tumour necrosis factors to stimulate branching morphologies in normal breast tissues. In breast cancer this process is disrupted facilitating tumour progression and metastasis and inhibiting apoptosis increasing the life of the metastatic cells. This paper highlights the role of matrix metalloproteinases in cell progression through the breast stroma and reviews the complex relationships between the different proteinases and their inhibitors in relation to breast cancer cells as they metastasise.

Exosome: emerging biomarker in breast cancer

Science.gov (United States)

Jia, Yunlu; Chen, Yongxia; Wang, Qinchuan; Jayasinghe, Ushani; Luo, Xiao; Wei, Qun; Wang, Ji; Xiong, Hanchu; Chen, Cong; Xu, Bin; Hu, Wenxian; Wang, Linbo; Zhao, Wenhe; Zhou, Jichun

2017-01-01

Exosomes are nano-sized membrane vesicles released by a variety of cell types, and are thought to play important roles in intercellular communications. In breast cancer, through horizontal transfer of various bioactive molecules, such as proteins and mRNAs, exosomes are emerging as local and systemic cell-to-cell mediators of oncogenic information and play an important role on cancer progression. This review outlines the current knowledge and concepts concerning the exosomes involvement in breast cancer pathogenesis (including tumor initiation, invasion and metastasis, angiogenesis, immune system modulation and tumor microenvironment) and cancer therapy resistance. Moreover, the potential use of exosomes as promising diagnostic and therapeutic biomarkers in breast cancer are also discussed. PMID:28402944

Periodic progress report, 6 months

DEFF Research Database (Denmark)

Juhl, Thomas Winther; Nielsen, Jakob Skov

This is the first progress report of the BriteEuram project named "High Power Laser Cutting for Heavy Industry" ("Powercut"). The report contains a summary of the objectives of the first period, an overview of the technical progress, a comparison between the planed and the accomplished work...

Decomposing productivity growth allowing efficiency gains and price-induced technical progress

NARCIS (Netherlands)

Oude Lansink, A.G.J.M.; Silva, E.; Stefanou, S.

2000-01-01

Time- and firm-specific output technical efficiency measures are generated within a price-induced technological change framework. The firm-specific production frontier incorporates past prices as an argument encouraging innovation and a time trend to account for exogenous technical change. The

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

Energy Technology Data Exchange (ETDEWEB)

Shih, Tzu-Ching [Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, 40402, Taiwan (China); Chen, Jeon-Hor; Nie Ke; Lin Muqing; Chang, Daniel; Nalcioglu, Orhan; Su, Min-Ying [Tu and Yuen Center for Functional Onco-Imaging and Radiological Sciences, University of California, Irvine, CA 92697 (United States); Liu Dongxu; Sun Lizhi, E-mail: shih@mail.cmu.edu.t [Department of Civil and Environmental Engineering, University of California, Irvine, CA 92697 (United States)

2010-07-21

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

Metastasis of breast cancer rectum

International Nuclear Information System (INIS)

Suárez, L.; Santander, G.

2004-01-01

Introduction: Metastases to the breast are rare, corresponding approximately to 3% of breast cancers. Primary tumors that spread more commonly are own breast, often following them in melanomas, neuroendocrine, ovarian and lymphoma. Medical history: A 59-year consultation rectoragias repeated and thinning. It is studied and finally intervenes (low anterior resection) diagnosed with rectal cancer whose Histopathology revealed a poorly differentiated adenocarcinoma stage III. Concomitantly the patient has a left breast lump that was studied with mammography, which revealed a dense mass of larger diameter 4 cm in topografiada 3 hour left breast with well defined contours and ultrasonographic structure solid. MI lumpectomy is performed whose pathology reports a poorly differentiated adenocarcinoma with cytoarchitectural features matching the lesion of rectum. Hormone receptors were negative. The patient is treated as a rectal cancer with RT spread over QT (5FU i /c). Died 7 months after diagnosis. Discusion: In literature are reported only 3 cases of breast metastases secondary to rectal cancer; how unusual this presentation justify this report.In this event they occurred in patients with a previous diagnosis of rectal cancer and in the context of systemic lesion progression. In our case clinician early diagnosis of rectal and breast metastases was synchronous. The mammographic image consistent with those described for these cases in the literature.The development of metastases in breast tissue is associated with a poor prognosis as which correlates with the survival of the patient

Targeted Therapy for Breast Cancer Prevention

Science.gov (United States)

den Hollander, Petra; Savage, Michelle I.; Brown, Powel H.

2013-01-01

With a better understanding of the etiology of breast cancer, molecularly targeted drugs have been developed and are being testing for the treatment and prevention of breast cancer. Targeted drugs that inhibit the estrogen receptor (ER) or estrogen-activated pathways include the selective ER modulators (tamoxifen, raloxifene, and lasofoxifene) and aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) have been tested in preclinical and clinical studies. Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer and promising results of AIs in breast cancer trials, suggest that AIs might be even more effective in the prevention of ER-positive breast cancer. However, these agents only prevent ER-positive breast cancer. Therefore, current research is focused on identifying preventive therapies for other forms of breast cancer such as human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer (TNBC, breast cancer that does express ER, progesterone receptor, or HER2). HER2-positive breast cancers are currently treated with anti-HER2 therapies including trastuzumab and lapatinib, and preclinical and clinical studies are now being conducted to test these drugs for the prevention of HER2-positive breast cancers. Several promising agents currently being tested in cancer prevention trials for the prevention of TNBC include poly(ADP-ribose) polymerase inhibitors, vitamin D, and rexinoids, both of which activate nuclear hormone receptors (the vitamin D and retinoid X receptors). This review discusses currently used breast cancer preventive drugs, and describes the progress of research striving to identify and develop more effective preventive agents for all forms of breast cancer. PMID:24069582

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.)

Assessment of intraoperative radiotherapy (IORT) in breast cancer. Guideline note. Technological evaluation report

International Nuclear Information System (INIS)

Daurat, Veronique

2015-10-01

The medical questions of this assessment focus on intraoperative radiotherapy (IORT), in women undergoing lumpectomy (breast-conserving surgery) and adjuvant radiotherapy for early breast cancer, in order for it to be refunded by the National Health Insurance. IORT was compared to standard whole-breast irradiation. Medical assessment questions have been grouped within 3 themes: 1. evaluation of conditions for achieving an IORT process (environment, technical platform, multidisciplinary organisation, risk management [anaesthetic, infectious, radiation protection, logistics/ technical] experience and training of professionals); 2. clinical benefit/risk ratio of the IORT in comparison with standard external breast irradiation; 3. population eligible for IORT treatment, with the highest standards in terms of risk factors in the current state of knowledge. The assessment method used in this report is based on: - a critical analysis of data from the selected literature identified through a systematic search; - gathering the viewpoints of relevant stakeholders (National Professional Boards of the medical and health professional domains, as well as national instances and patient associations of the domain). In conclusion, the available data are not mature enough to demonstrate that IORT is useful in adjuvant conservative breast cancer treatment in comparison with standard external whole breast irradiation. As a consequence, at this stage, the elements are not gathered to support IORT payment by National Health Insurance. Long-term data from clinical and medico-economic studies are needed to prove clinical utility of the IORT in early breast cancer. HAS recommends eventually that IORT is performed exclusively in the context of clinical research in breast cancer

Angiogenesis - a crucial step in breast cancer growth, progression and dissemination by Raman imaging

Science.gov (United States)

Kopeć, Monika; Abramczyk, Halina

2018-06-01

Combined micro-Raman imaging and AFM imaging are efficient methods for analyzing human tissue due to their high spatial and spectral resolution as well as sensitivity to subtle chemical, structural and topographical changes. The aim of this study was to determine biochemical composition and mechanical topography around blood vessels in the tumor mass of human breast tissue. Significant alterations of the chemical composition and structural architecture around the blood vessel were found compared to the normal breast tissue. A pronounced increase of collagen-fibroblast-glycocalyx network, as well as enhanced lactic acid, and glycogen activity in patients affected by breast cancer were reported.

Biomarkers of the Metabolic Syndrome and Breast Cancer Prognosis

International Nuclear Information System (INIS)

Zhu, Qiu-Li; Xu, Wang-Hong; Tao, Meng-Hua

2010-01-01

In spite of its public health importance, our understanding of the mechanisms of breast carcinogenesis and progress is still evolving. The metabolic syndrome (MS) is a constellation of biochemical abnormalities including visceral adiposity, hyperglycemia, hyperinsulinemia, dyslipidemia and high blood pressure. The components of the MS have all been related to late-stage disease and even to a poor prognosis of breast cancer through multiple interacting mechanisms. In this review, we aim to present a summary of recent advances in the understanding of the contribution of the MS to breast cancer with the emphasis on the role of biomarkers of the MS in the prognosis of breast cancer

Biomarkers of the Metabolic Syndrome and Breast Cancer Prognosis

Energy Technology Data Exchange (ETDEWEB)

Zhu, Qiu-Li; Xu, Wang-Hong [Department of Epidemiology, School of Public Health, Fudan University, Shanghai 200032 (China); Tao, Meng-Hua [Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY 14214 (United States)

2010-04-28

In spite of its public health importance, our understanding of the mechanisms of breast carcinogenesis and progress is still evolving. The metabolic syndrome (MS) is a constellation of biochemical abnormalities including visceral adiposity, hyperglycemia, hyperinsulinemia, dyslipidemia and high blood pressure. The components of the MS have all been related to late-stage disease and even to a poor prognosis of breast cancer through multiple interacting mechanisms. In this review, we aim to present a summary of recent advances in the understanding of the contribution of the MS to breast cancer with the emphasis on the role of biomarkers of the MS in the prognosis of breast cancer.

PFBC HGCU Test Facility. Technical progress report No. 24, Third quarter, CY 1995

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-10-01

This is the twenty-fourth and final Technical Progress Report submitted to the Department of Energy (DOE) in connection with the cooperative agreement between the DOE and Ohio Power Company for the Tidd PFBC Hot Gas Clean Up Test Facility. This report covers the work completed during the Third Quarter of CY 1995. All activity this quarter was directed toward the completion of the program final report. A draft copy of the final report was forwarded to DOE during this quarter, and DOE submitted their comments on the report to AEPSC. DOE requested that Westinghouse write an appendix to the report covering the performance of the fail-safe regenerator devices during Tad operation, and Westinghouse subsequently prepared the appendix. Additional DOE comments were incorporated into the report, and it will be issued in camera-ready form by the end of October, 1995, which is the program end date. Appendix 1 presents the results of filter candle posttest examination by Westinghouse performed on selected filter candles following final shutdown of the system.

Do myoepithelial cells hold the key for breast tumorprogression?

Energy Technology Data Exchange (ETDEWEB)

Polyak, Kornelia; Hu, Min

2005-11-18

Mammary myoepithelial cells have been the foster child of breast cancer biology and have been largely ignored since they were considered to be less important for tumorigenesis than luminal epithelial cells from which most of breast carcinomas are thought to arise. In recent years as our knowledge in stem cell biology and the cellular microenvironment has been increasing myoepithelial cells are slowly starting to gain more attention. Emerging data raise the hypothesis if myoepithelial cells play a key role in breast tumor progression by regulating the in situ to invasive carcinoma transition and if myoepithelial cells are part of the mammary stem cell niche. Paracrine interactions between myoepithelial and luminal epithelial cells are known to be important for cell cycle arrest, establishing epithelial cell polarity, and inhibiting migration and invasion. Based on these functions normal mammary myoepithelial cells have been called ''natural tumor suppressors''. However, during tumor progression myoepithelial cells seem to loose these properties and eventually they themselves diminish as tumors become invasive. Better understanding of myoepithelial cell function and their role in tumor progression may lead to their exploitation for cancer therapeutic and preventative measures.

Loss of cadherin-based cell adhesion and the progression of Invasive Lobular Breast Cancer

NARCIS (Netherlands)

Vlug, E.J.

2015-01-01

Lobular breast cancer is a type of breast cancer that is histologically characterized by a noncohesive growth pattern of small regular cells, where single cells infiltrate as one-layered strands of cells. This noncohesive growth pattern is due to inactivation of the E-cadherin complex and a

Randomized controlled trial to evaluate the effects of combined progressive exercise on metabolic syndrome in breast cancer survivors: rationale, design, and methods.

Science.gov (United States)

Dieli-Conwright, Christina M; Mortimer, Joanne E; Schroeder, E Todd; Courneya, Kerry; Demark-Wahnefried, Wendy; Buchanan, Thomas A; Tripathy, Debu; Bernstein, Leslie

2014-04-03

Metabolic syndrome (MetS) is increasingly present in breast cancer survivors, possibly worsened by cancer-related treatments, such as chemotherapy. MetS greatly increases risk of cardiovascular disease and diabetes, co-morbidities that could impair the survivorship experience, and possibly lead to cancer recurrence. Exercise has been shown to positively influence quality of life (QOL), physical function, muscular strength and endurance, reduce fatigue, and improve emotional well-being; however, the impact on MetS components (visceral adiposity, hyperglycemia, low serum high-density lipoprotein cholesterol, hypertriglyceridemia, and hypertension) remains largely unknown. In this trial, we aim to assess the effects of combined (aerobic and resistance) exercise on components of MetS, as well as on physical fitness and QOL, in breast cancer survivors soon after completing cancer-related treatments. This study is a prospective randomized controlled trial (RCT) investigating the effects of a 16-week supervised progressive aerobic and resistance exercise training intervention on MetS in 100 breast cancer survivors. Main inclusion criteria are histologically-confirmed breast cancer stage I-III, completion of chemotherapy and/or radiation within 6 months prior to initiation of the study, sedentary, and free from musculoskeletal disorders. The primary endpoint is MetS; secondary endpoints include: muscle strength, shoulder function, cardiorespiratory fitness, body composition, bone mineral density, and QOL. Participants randomized to the Exercise group participate in 3 supervised weekly exercise sessions for 16 weeks. Participants randomized to the Control group are offered the same intervention after the 16-week period of observation. This is the one of few RCTs examining the effects of exercise on MetS in breast cancer survivors. Results will contribute a better understanding of metabolic disease-related effects of resistance and aerobic exercise training and inform

Randomized controlled trial to evaluate the effects of combined progressive exercise on metabolic syndrome in breast cancer survivors: rationale, design, and methods

International Nuclear Information System (INIS)

Dieli-Conwright, Christina M; Mortimer, Joanne E; Schroeder, E Todd; Courneya, Kerry; Demark-Wahnefried, Wendy; Buchanan, Thomas A; Tripathy, Debu; Bernstein, Leslie

2014-01-01

Metabolic syndrome (MetS) is increasingly present in breast cancer survivors, possibly worsened by cancer-related treatments, such as chemotherapy. MetS greatly increases risk of cardiovascular disease and diabetes, co-morbidities that could impair the survivorship experience, and possibly lead to cancer recurrence. Exercise has been shown to positively influence quality of life (QOL), physical function, muscular strength and endurance, reduce fatigue, and improve emotional well-being; however, the impact on MetS components (visceral adiposity, hyperglycemia, low serum high-density lipoprotein cholesterol, hypertriglyceridemia, and hypertension) remains largely unknown. In this trial, we aim to assess the effects of combined (aerobic and resistance) exercise on components of MetS, as well as on physical fitness and QOL, in breast cancer survivors soon after completing cancer-related treatments. This study is a prospective randomized controlled trial (RCT) investigating the effects of a 16-week supervised progressive aerobic and resistance exercise training intervention on MetS in 100 breast cancer survivors. Main inclusion criteria are histologically-confirmed breast cancer stage I-III, completion of chemotherapy and/or radiation within 6 months prior to initiation of the study, sedentary, and free from musculoskeletal disorders. The primary endpoint is MetS; secondary endpoints include: muscle strength, shoulder function, cardiorespiratory fitness, body composition, bone mineral density, and QOL. Participants randomized to the Exercise group participate in 3 supervised weekly exercise sessions for 16 weeks. Participants randomized to the Control group are offered the same intervention after the 16-week period of observation. This is the one of few RCTs examining the effects of exercise on MetS in breast cancer survivors. Results will contribute a better understanding of metabolic disease-related effects of resistance and aerobic exercise training and inform

Affinity proteomic profiling of plasma for proteins associated to area-based mammographic breast density.

Science.gov (United States)

Byström, Sanna; Eklund, Martin; Hong, Mun-Gwan; Fredolini, Claudia; Eriksson, Mikael; Czene, Kamila; Hall, Per; Schwenk, Jochen M; Gabrielson, Marike

2018-02-14

Mammographic breast density is one of the strongest risk factors for breast cancer, but molecular understanding of how breast density relates to cancer risk is less complete. Studies of proteins in blood plasma, possibly associated with mammographic density, are well-suited as these allow large-scale analyses and might shed light on the association between breast cancer and breast density. Plasma samples from 1329 women in the Swedish KARMA project, without prior history of breast cancer, were profiled with antibody suspension bead array (SBA) assays. Two sample sets comprising 729 and 600 women were screened by two different SBAs targeting a total number of 357 proteins. Protein targets were selected through searching the literature, for either being related to breast cancer or for being linked to the extracellular matrix. Association between proteins and absolute area-based breast density (AD) was assessed by quantile regression, adjusting for age and body mass index (BMI). Plasma profiling revealed linear association between 20 proteins and AD, concordant in the two sets of samples (p density and processes of tissue homeostasis, DNA repair, cancer development and/or progression in breast cancer. Further validation and follow-up studies of the shortlisted protein candidates in independent cohorts will be needed to infer their role in breast density and its progression in premenopausal and postmenopausal women.

Global Breast Cancer: The Lessons to Bring Home

International Nuclear Information System (INIS)

Formenti, S.C.; Formenti, S.C.; Arslan, A.A.; Arslan, A.A.; Love, S.M.; Love, S.M.

2012-01-01

Breast cancer is the most common cancer affecting women globally. This paper discusses the current progress in breast cancer in Western countries and focuses on important differences of this disease in low- and middle-income countries (LMCs). It introduces several arguments for applying caution before globalizing some of the US-adopted practices in the screening and management of the disease. Finally, it suggests that studies of breast cancer in LMCs might offer important insights for a more effective management of the problem both in developing as well as developed countries.high-energy Japanese immigrants female higher proliferative

Inhibition of heregulin expression blocks tumorigenicity and metastasis of breast cancer

Energy Technology Data Exchange (ETDEWEB)

Tsai, Miaw-Sheue; Shamon-Taylor, Lisa A.; Mehmi, Inderjit; Tang, Careen K.; Cardillo, Marina; Lupu, Ruth

2001-12-20

The growth factor Heregulin (HRG) is expressed in 30% of breast cancer tumors. HRG induces tumorigenicity and metastasis of breast cancer cells. Our investigation into whether blockage of HRG reduces the aggressiveness of breast cancer cells demonstrated that transfection of MDA-MB-231 with an HRG antisense cDNA suppressed proliferation, tumorigenicity, and metastasis. Blockage of the aggressive phenotype is mediated possibly through inactivation of the erbB signaling pathways and a decrease in MMP-9 activity. Our study is the first to report that HRG is a key promoter of breast cancer progression and should be deemed as a potential target in developing therapies for the treatment of breast carcinomas.

Technical evaluation of Virtual Touch™ tissue quantification and elastography in benign and malignant breast tumors

Science.gov (United States)

JIANG, QUAN; ZHANG, YUAN; CHEN, JIAN; ZHANG, YUN-XIAO; HE, ZHU

2014-01-01

The aim of this study was to investigate the diagnostic value of the Virtual Touch™ tissue quantification (VTQ) and elastosonography technologies in benign and malignant breast tumors. Routine preoperative ultrasound, elastosonography and VTQ examinations were performed on 86 patients with breast lesions. The elastosonography score and VTQ speed grouping of each lesion were measured and compared with the pathological findings. The difference in the elastosonography score between the benign and malignant breast tumors was statistically significant (Pbenign and malignant tumors was also statistically significant (P<0.05). In addition, the diagnostic accuracy of conventional ultrasound, elastosonography, VTQ technology and the combined methods showed statistically significant differences (P<0.05). The use of the three technologies in combination significantly improved the diagnostic accuracy to 91.86%. In conclusion, the combination of conventional ultrasound, elastosonography and VTQ technology can significantly improve accuracy in the diagnosis of breast cancer. PMID:25187797

High Throughput Analysis of Breast Cancer Specimens on the Grid

OpenAIRE

Yang, Lin; Chen, Wenjin; Meer, Peter; Salaru, Gratian; Feldman, Michael D.; Foran, David J.

2007-01-01

Breast cancer accounts for about 30% of all cancers and 15% of all cancer deaths in women in the United States. Advances in computer assisted diagnosis (CAD) holds promise for early detecting and staging disease progression. In this paper we introduce a Grid-enabled CAD to perform automatic analysis of imaged histopathology breast tissue specimens. More than 100,000 digitized samples (1200 × 1200 pixels) have already been processed on the Grid. We have analyzed results for 3744 breast tissue ...

Functional screen for genes responsible for tamoxifen resistance in human breast cancer cells

NARCIS (Netherlands)

Meijer, Danielle; van Agthoven, Ton; Bosma, Peter T.; Nooter, Kees; Dorssers, Lambert C. J.

2006-01-01

Antiestrogens, such as tamoxifen, are widely used for endocrine treatment of estrogen receptor-positive breast cancer. However, as breast cancer progresses, development of tamoxifen resistance is inevitable. The mechanisms underlying this resistance are not well understood. To identify genes

Cell-Cell Adhesion and Insulin-Like Growth Factor I Receptor in Breast Cancer

National Research Council Canada - National Science Library

Bartucci, Monica

2001-01-01

.... Our goal was to study the role of the insulin-like growth factor I receptor (IGF-IR) in breast cancer. The IGF-IR is a multifunctional tyrosine kinase that has been recently implicated in breast tumor development and progression...

Circulating tumor cells, disease recurrence and survival in newly diagnosed breast cancer

NARCIS (Netherlands)

Franken, Bas; De Groot, Marco R.; Mastboom, Walter J.B.; Vermes, I.; van der Palen, Jacobus Adrianus Maria; Tibbe, Arjan G.J.; Terstappen, Leonardus Wendelinus Mathias Marie

2012-01-01

Introduction The presence of circulating tumor cells (CTC) is an independent prognostic factor for progression-free survival and breast cancer-related death (BRD) for patients with metastatic breast cancer beginning a new line of systemic therapy. The current study was undertaken to explore whether

First line chemotherapy plus trastuzumab in metastatic breast cancer ...

African Journals Online (AJOL)

First line chemotherapy plus trastuzumab in metastatic breast cancer HER2 positive - Observational institutional study. ... The progression free survival was estimated by the Kaplan-Meier method, from the date of first cycle to the date of progression or at the last consultation, and the median was 12.8 months. Trastuzumab ...

[Public policy-making on breast cancer in Latin America].

Science.gov (United States)

González-Robledo, M C; González-Robledo, L M; Nigenda, G

2013-03-01

To understand the public policy-making process as it relates to breast cancer care in five Latin American countries. An exploratory-evaluative study was conducted in Argentina, Brazil, Colombia, Mexico, and Venezuela in 2010, with the selection of countries based on convenience sampling. Sixty-five semi-structured interviews were conducted with government officials, academics, and representatives of trade associations and civil society organizations. A content analysis of secondary sources was performed. Information sources, data, and informants were mixed using the triangulation method for purposes of analysis. The countries that have made the most progress in public policy-making related to breast cancer are Brazil and Mexico. Although Argentina, Colombia, and Venezuela do not have policies, they do have breast cancer care programs and activities. Two perspectives on the development of public policies became evident: the first includes the broad participation of both governmental and nongovernmental sectors, whereas the second, more narrow approach involves government authorities alone. The results point to significant differences in public policy-making related to breast cancer in the Region. They also show that greater progress has been made in countries where policies have been developed through inclusive participation processes.

From Community Laywomen to Breast Health Workers: A Pilot Training Model to Implement Clinical Breast Exam Screening in Malawi.

Science.gov (United States)

Gutnik, Lily; Moses, Agnes; Stanley, Christopher; Tembo, Tapiwa; Lee, Clara; Gopal, Satish

2016-01-01

Breast cancer burden is high in low-income countries. Inadequate early detection contributes to late diagnosis and increased mortality. We describe the training program for Malawi's first clinical breast exam (CBE) screening effort. Laywomen were recruited as Breast Health Workers (BHWs) with the help of local staff and breast cancer advocates. The four-week training consisted of lectures, online modules, role-playing, case discussions, CBE using simulators and patients, and practice presentations. Ministry of Health trainers taught health communication, promotion, and education skills. Breast cancer survivors shared their experiences. Clinicians taught breast cancer epidemiology, prevention, detection, and clinical care. Clinicians and research staff taught research ethics, informed consent, data collection, and professionalism. Breast cancer knowledge was measured using pre- and post-training surveys. Concordance between BHW and clinician CBE was assessed. Breast cancer talks by BHW were evaluated on a 5-point scale in 22 areas by 3 judges. We interviewed 12 women, and 4 were selected as BHWs including 1 breast cancer survivor. Training was dynamic with modification based on trainee response and progress. A higher-than-anticipated level of comprehension and interest led to inclusion of additional topics like breast reconstruction. Pre-training knowledge increased from 49% to 91% correct (peducational talks was 4.4 (standard deviation 0.7). Malawian laywomen successfully completed training and demonstrated competency to conduct CBE and deliver breast cancer educational talks. Knowledge increased after training, and concordance was high between BHW and clinician CBE.

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

Directory of Open Access Journals (Sweden)

Ellen Ordinario

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

Appropriability, Technological Opportunity, Market Demand, and Technical Change - Empirical Evidence from Switzerland

OpenAIRE

Harabi, Najib

1992-01-01

The purpose of this paper is to analyze both theoretically and empirically those factors which underlay the - empirically observable - inter-industry differences in technical progress. At the theoretical level economists agree more and more that technical progress can be explained at the industry level by the following three factors: (1) the technological opportunities, (2) the appropriability conditions, meaning the ability to capture and protect the results of technical innovations and (3) ...

Inflammatory breast cancer

International Nuclear Information System (INIS)

Wagnerova, M.

2012-01-01

Inflammatory breast cancer (IBC) is an extremely aggressive disease that progresses rapidly and carries a very grim prognosis. It is characterized by erythema, rapid enlargement of the breast, skin ridging, and a characteristics peau d´orange appearance of the skin secondary to dermal lymphatic tumor involvement. Although a palpable tumor may not by present, about 55% to 85% of patient will present with metastases to the axillary or supraclavicular lymph nodes. Diagnosis of IBC is made on the basis of these clinical characteristics, as well as histologic verification of carcinoma. Accurate diagnosis is critically important, as multimodal therapy can significantly improve outcome if instituted early enough. Primary systemic treatment (neoadjuvant, induction, initials) is standard treatment for inflammatory breast cancer. If treatment response is not satisfactory it is necessary to look for new treatment regimens with different concept of dose intensity, density and sequence of treatment. In the neoadjuvant setting it is possible to employ all targeted and non-targeted therapies as was shown in a number of clinical trials. (author)

Role of tumor microenvironment in triple-negative breast cancer and its prognostic significance

Institute of Scientific and Technical Information of China (English)

Tianjian Yu; Genhong Di

2017-01-01

Breast cancer has been shown to live in the tumor microenvironment,which consists of not only breast cancer cells themselves but also a significant amount of pathophysiologically altered surrounding stroma and cells.Diverse components of the breast cancer microenvironment,such as suppressive immune cells,re-programmed fibroblast cells,altered extracellular matrix (ECM) and certain soluble factors,synergistically impede an effective anti-tumor response and promote breast cancer progression and metastasis.Among these components,stromal cells in the breast cancer microenvironment are characterized by molecular alterations and aberrant signaling pathways,whereas the ECM features biochemical and biomechanical changes.However,triple-negative breast cancer (TNBC),the most aggressive subtype of this disease that lacks effective therapies available for other subtypes,is considered to feature a unique microenvironment distinct from that of other subtypes,especially compared to Luminal A subtype.Because these changes are now considered to significantly impact breast cancer development and progression,these unique alterations may serve as promising prognostic factors of clinical outcome or potential therapeutic targets for the treatment of TNBC.In this review,we focus on the composition of the TNBC microenvironment,concomitant distinct biological alteration,specific interplay between various cell types and TNBC cells,and the prognostic implications of these findings.

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.

Profile of palbociclib in the treatment of metastatic breast cancer

Directory of Open Access Journals (Sweden)

Ehab M

2016-05-01

Full Text Available Moataz Ehab,1 Mohamad Elbaz2,31Department of Pharmacy Practice, 2Department of Pharmacology, Pharmacy School, Helwan University, Egypt; 3Department of Pathology, The Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USAAbstract: Breast cancer is the most common cancer diagnosed in women. Each year, thousands die either because of disease progression or failure of treatment. Breast cancer is classified into different subtypes based on the molecular expression of estrogen receptor (ER, progesterone receptor, and/or human epidermal growth factor receptor 2 (HER2. These receptors represent important therapeutic targets either through monoclonal antibodies or through small-molecule inhibitors directed toward them. However, up to 40% of patients develop either a primary or a secondary resistance to the current treatments. Therefore, there is an urgent need for investigating new targets in order to overcome the resistance and/or enhance the current therapies. Cell cycle is altered in many human cancers, especially in breast cancer. Cyclin-dependent kinases (CDKs, especially CDK4 and CDK6, play a pivotal role in cell cycle progression that makes them potential targets for new promising therapies. CDK inhibition has shown strong antitumor activities, ranging from cytostatic antiproliferative effects to synergistic effects in combination with other antitumor drugs. In order to overcome the drawbacks of the first-generation CDK inhibitors, recently, new CDK inhibitors have emerged that are more selective to CDK4 and CDK6 such as palbociclib, which is the most advanced CDK4/6 inhibitor in trials. In preclinical studies, palbociclib has shown a very promising antitumor activity, especially against ERα+ breast cancer subtype. Palbociclib has gained world attention, and US the Food and Drug Administration has accelerated its approval for first-line treatment in combination with letrozole for the first-line systematic

Quality of life in patients with recurrent breast cancer after second breast-conserving therapy in comparison with mastectomy: the German experience.

Science.gov (United States)

Jendrian, Svenja; Steffens, Katharina; Schmalfeldt, Barbara; Laakmann, Elena; Bergelt, Corinna; Witzel, Isabell

2017-06-01

Although some studies suggest that breast-conserving therapy (BCT) shows better psychosocial outcomes than mastectomy in patients with primary breast cancer, little is known about the outcomes of these surgical options in recurrent breast cancer. We investigated differences in overall survival and re-recurrence rates as well as psychosocial outcomes among patients who underwent BCT or mastectomy after the diagnosis of recurrent breast cancer in a single-center setting. 124 of 186 eligible patients who underwent surgical treatment for breast cancer recurrence completed the questionnaires on quality of life (EORTC QLQ-C30 and -BR23), fear of progression (PA-F-KF), anxiety and depression (HADS), and body image (BIS). Women after breast-conserving surgery (n = 46) showed significantly better outcomes than women after mastectomy (n = 61) with respect to body image (P quality of life were partnership (OR 2.46), higher monthly family income (OR 3.54), and higher professional qualification (OR 4.3) in our group of patients. Our results indicate that patients treated with breast-conserving therapy after recurrent breast cancer perceive lower impairments in body image and several aspects of quality of life than patients treated with mastectomy.

Increased utilization of fructose has a positive effect on the development of breast cancer

Directory of Open Access Journals (Sweden)

Xiajing Fan

2017-09-01

Full Text Available Rapid proliferation and Warburg effect make cancer cells consume plenty of glucose, which induces a low glucose micro-environment within the tumor. Up to date, how cancer cells keep proliferating in the condition of glucose insufficiency still remains to be explored. Recent studies have revealed a close correlation between excessive fructose consumption and breast cancer genesis and progression, but there is no convincing evidence showing that fructose could directly promote breast cancer development. Herein, we found that fructose, not amino acids, could functionally replace glucose to support proliferation of breast cancer cells. Fructose endowed breast cancer cells with the colony formation ability and migratory capacity as effective as glucose. Interestingly, although fructose was readily used by breast cancer cells, it failed to restore proliferation of non-tumor cells in the absence of glucose. These results suggest that fructose could be relatively selectively employed by breast cancer cells. Indeed, we observed that a main transporter of fructose, GLUT5, was highly expressed in breast cancer cells and tumor tissues but not in their normal counterparts. Furthermore, we demonstrated that the fructose diet promoted metastasis of 4T1 cells in the mouse models. Taken together, our data show that fructose can be used by breast cancer cells specifically in glucose-deficiency, and suggest that the high-fructose diet could accelerate the progress of breast cancer in vivo.

High temperature turbine technology program. Phase II. Technology test and support studies. Annual technical progress report, January 1, 1979-December 31, 1979

Energy Technology Data Exchange (ETDEWEB)

1980-01-01

Work performed on the High Temperature Turbine Technology Program, Phase II - Technology Test and Support Studies during the period from January 1, 1979 through December 31, 1979 is summarized. Objectives of the program elements as well as technical progress and problems encountered during this Phase II annual reporting period are presented. Progress on design, fabrication and checkout of test facilities and test rigs is described. LP turbine cascade tests were concluded. 350 hours of testing were conducted on the LP rig engine first with clean distillate fuel and then with fly ash particulates injected into the hot gas stream. Design and fabrication of the turbine spool technology rig components are described. TSTR 60/sup 0/ sector combustor rig fabrication and testing are reviewed. Progress in the design and fabrication of TSTR cascade rig components for operation on both distillate fuel and low Btu gas is described. The new coal-derived gaseous fuel synthesizing facility is reviewed. Results and future plans for the supporting metallurgical programs are discussed.

GPHS-RTGs in support of the Cassini mission. Semi annual technical progress report, 2 October 1995--31 March 1996

International Nuclear Information System (INIS)

1996-01-01

The technical progress achieved during the period 2 October 1995 through 31 March 1996 on Contract No. DE-AC03-91SF18852, Radioisotope Generators and Ancillary Activities is described herein. This report is organized by the program task structure as follows: spacecraft integration and liaison; engineering support; safety; qualified unicouple fabrication; ETG fabrication, assembly, and test; ground support equipment (GSE); RTG shipping and launch support; designs, reviews, and mission applications; project management, quality assurance and reliability, contract changes, non-capital CAGO acquisition, and CAGO maintenance; contract acquired government-owned property (CAGO) acquisition; and program calendars

Polydimethylsiloxane: a new contrast material for localization of occult breast lesions

International Nuclear Information System (INIS)

Vitral, Geraldo Sérgio Farinazzo; Raposo, Nádia Rezende Barbosa

2011-01-01

The radioguided localization of occult breast lesions (ROLL) technique often utilizes iodinated radiographic contrast to assure that the local injection of 99m Tc-MAA corresponds to the location of the lesion under investigation. However, for this application, this contrast has several shortcomings. The objective of this study was to evaluate the safety, effectiveness and technical feasibility of the use of polydimethylsiloxane (PDMS) as radiological contrast and tissue marker in ROLL. The safety assessment was performed by the acute toxicity study in Wistar rats (n = 50). The radiological analysis of breast tissue (n = 32) from patients undergoing reductive mammoplasty was used to verify the effectiveness of PDMS as contrast media. The technical feasibility was evaluated through the scintigraphic and histologic analysis. We found no toxic effects of PDMS for this use during the observational period. It has been demonstrated in human breast tissue that the average diameter of the tissue marked by PDMS was lower than when marked by the contrast medium (p <0.001). PDMS did not interfere with the scintigraphic uptake (p = 0.528) and there was no injury in histological processing of samples. This study demonstrated not only the superiority of PDMS as radiological contrast in relation to the iodinated contrast, but also the technical feasibility for the same applicability in the ROLL

The Japanese Guidelines for Breast Cancer Screening.

Science.gov (United States)

Hamashima, Chisato; Hamashima C, Chisato; Hattori, Masakazu; Honjo, Satoshi; Kasahara, Yoshio; Katayama, Takafumi; Nakai, Masahiro; Nakayama, Tomio; Morita, Takako; Ohta, Koji; Ohnuki, Koji; Sagawa, Motoyasu; Saito, Hiroshi; Sasaki, Seiju; Shimada, Tomoyuki; Sobue, Tomotaka; Suto, Akihiko

2016-05-01

The incidence of breast cancer has progressively increased, making it the leading cause of cancer deaths in Japan. Breast cancer accounts for 20.4% of all new cancers with a reported age-standardized rate of 63.6 per 100 000 women. The Japanese guidelines for breast cancer screening were developed based on a previously established method. The efficacies of mammography with and without clinical breast examination, clinical breast examination and ultrasonography with and without mammography were evaluated. Based on the balance of the benefits and harms, recommendations for population-based and opportunistic screenings were formulated. Five randomized controlled trials of mammographic screening without clinical breast examination were identified for mortality reduction from breast cancer. The overall relative risk for women aged 40-74 years was 0.75 (95% CI: 0.67-0.83). Three randomized controlled trials of mammographic screening with clinical breast examination served as eligible evidence for mortality reduction from breast cancer. The overall relative risk for women aged 40-64 years was 0.87 (95% confidence interval: 0.77-0.98). The major harms of mammographic screening were radiation exposure, false-positive cases and overdiagnosis. Although two case-control studies evaluating mortality reduction from breast cancer were found for clinical breast examination, there was no study assessing the effectiveness of ultrasonography for breast cancer screening. Mammographic screening without clinical breast examination for women aged 40-74 years and with clinical breast examination for women aged 40-64 years is recommended for population-based and opportunistic screenings. Clinical breast examination and ultrasonography are not recommended for population-based screening because of insufficient evidence regarding their effectiveness. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Clinical significance of Mena and Her-2 expression in breast cancer.

Science.gov (United States)

Du, J W; Xu, K Y; Fang, L Y; Qi, X L

2012-01-01

The aim of this study was to determine the expression patterns of Mena and Her-2 in breast cancer tissues and to explore their clinical significance and correlation with clinicopathological parameters. The expression of Mena and Her-2 was detected in 40 breast cancer tissues and 14 normal breast tissues by immunohistochemistry, and the relationship of Mena and Her-2 expression with clinicopathological parameters was analyzed. Both Mena (70%) and Her-2 (40%) were more commonly expressed in breast cancer than in normal breast tissue (7.1%, 0%, respectively; p Mena and Her-2 expression in breast cancer were positively correlated (r = 0.530, p Mena and Her-2 were both associated with axillary lymph node metastasis and TNM stage (p Mena and Her-2 are related to the malignancy degree and metastasis of breast cancer, and thus may play a coordinating role in the occurrence and progression of breast cancer.

Interleukin 8 in progression of hormone-dependent early breast cancer

Indian Academy of Sciences (India)

2017-04-18

Apr 18, 2017 ... significance of IL8 in hormone-dependent breast cancer. The aim of this study was to evaluate the prognostic ... types characterized by a particularly poor prognosis (Aceto et al. ... Progesterone receptor status. PRlow. 70. 76.9. PRhigh. 21. 23.1. NA .... (M<88.82 pg/mg) had lower percentage of relapses and.

Current therapeutic strategies of anti-HER2 treatment in advanced breast cancer patients

Directory of Open Access Journals (Sweden)

Joanna Huszno

2016-03-01

Full Text Available The HER2/neu ( ERBB2 oncogene is amplified and/or overexpressed in approximately 20% of breast cancers, and is a strong prognostic factor for relapse and poor overall survival, particularly in node-positive patients. It is also an important predictor for response to trastuzumab, which has established efficacy against breast cancer with overexpression or amplification of the HER2 oncogene. Treatment with the anti-HER2 humanized monoclonal antibody – trastuzumab significantly improves progression-free and overall survival among patients with HER2-positive breast cancer. However, in most patients with HER2-positive metastatic breast cancer, the disease progresses occurred, what cause the need for new targeted therapies for advanced disease. In clinical trials, there are tested new drugs to improve the results of treatment for this group of patients. This paper presents new drugs introduced into clinical practice for treatment of advanced breast cancer, whose molecular target are receptors of the HER2 family. In addition, new therapeutic strategies and drugs that are currently in clinical researches are discussed.

Integrated Development of Serum Molecular Markers for Early Diagnosis of Breast Cancer

Science.gov (United States)

2006-09-01

development of breast cancer screening test. Increasing our understanding of the role of biomarkers in the etiology and progression of breast cancer...granulocyte-colony-stimulating factor in normal pregnancy and preeclampsia . Hypertens Pregnancy 1999;18:95 – 106. 50. Bux J, Hofmann C, Welte K. Serum G-CSF

Intersection of FOXO- and RUNX1-mediated gene expression programs in single breast epithelial cells during morphogenesis and tumor progression.

Science.gov (United States)

Wang, Lixin; Brugge, Joan S; Janes, Kevin A

2011-10-04

Gene expression networks are complicated by the assortment of regulatory factors that bind DNA and modulate transcription combinatorially. Single-cell measurements can reveal biological mechanisms hidden by population averages, but their value has not been fully explored in the context of mRNA regulation. Here, we adapted a single-cell expression profiling technique to examine the gene expression program downstream of Forkhead box O (FOXO) transcription factors during 3D breast epithelial acinar morphogenesis. By analyzing patterns of mRNA fluctuations among individual matrix-attached epithelial cells, we found that a subset of FOXO target genes was jointly regulated by the transcription factor Runt-related transcription factor 1 (RUNX1). Knockdown of RUNX1 causes hyperproliferation and abnormal morphogenesis, both of which require normal FOXO function. Down-regulating RUNX1 and FOXOs simultaneously causes widespread oxidative stress, which arrests proliferation and restores normal acinar morphology. In hormone-negative breast cancers lacking human epidermal growth factor receptor 2 (HER2) amplification, we find that RUNX1 down-regulation is strongly associated with up-regulation of FOXO1, which may be required to support growth of RUNX1-negative tumors. The coordinate function of these two tumor suppressors may provide a failsafe mechanism that inhibits cancer progression.

ISABELLE: a progress report

Energy Technology Data Exchange (ETDEWEB)

Hahn, H

1980-01-01

This paper discusses the ISABELLE project, which has the objective of constructing a high-energy proton colliding beam facility at Brookhaven National Laboratory. The major technical features of the intersecting storage accelerators with their projected performance are described. Application of over 1000 superconducting magnets in the two rings represents the salient characteristic of the machine. The status of the entire project, the technical progress made so far, and difficulties encountered are reviewed.

ISABELLE: a progress report

International Nuclear Information System (INIS)

Hahn, H.

1980-01-01

This paper discusses the ISABELLE project, which has the objective of constructing a high-energy proton colliding beam facility at Brookhaven National Laboratory. The major technical features of the intersecting storage accelerators with their projected performance are described. Application of over 1000 superconducting magnets in the two rings represents the salient characteristic of the machine. The status of the entire project, the technical progress made so far, and difficulties encountered are reviewed

Coagulation factor VIIa-mediated protease-activated receptor 2 activation leads to β-catenin accumulation via the AKT/GSK3β pathway and contributes to breast cancer progression.

Science.gov (United States)

Roy, Abhishek; Ansari, Shabbir A; Das, Kaushik; Prasad, Ramesh; Bhattacharya, Anindita; Mallik, Suman; Mukherjee, Ashis; Sen, Prosenjit

2017-08-18

Cell migration and invasion are very characteristic features of cancer cells that promote metastasis, which is one of the most common causes of mortality among cancer patients. Emerging evidence has shown that coagulation factors can directly mediate cancer-associated complications either by enhancing thrombus formation or by initiating various signaling events leading to metastatic cancer progression. It is well established that, apart from its distinct role in blood coagulation, coagulation factor FVIIa enhances aggressive behaviors of breast cancer cells, but the underlying signaling mechanisms still remain elusive. To this end, we investigated FVIIa's role in the migration and invasiveness of the breast cancer cell line MDA-MB-231. Consistent with previous observations, we observed that FVIIa increased the migratory and invasive potential of these cells. We also provide molecular evidence that protease-activated receptor 2 activation followed by PI3K-AKT activation and GSK3β inactivation is involved in these processes and that β-catenin, a well known tumor-regulatory protein, contributes to this signaling pathway. The pivotal role of β-catenin was further indicated by the up-regulation of its downstream targets cyclin D1, c-Myc, COX-2, MMP-7, MMP-14, and Claudin-1. β-Catenin knockdown almost completely attenuated the FVIIa-induced enhancement of breast cancer migration and invasion. These findings provide a new perspective to counteract the invasive behavior of breast cancer, indicating that blocking PI3K-AKT pathway-dependent β-catenin accumulation may represent a potential therapeutic approach to control breast cancer. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

The general technical regulation and the standardization

International Nuclear Information System (INIS)

Laverie, Michel; Houze, Christian; Lebouleux, Philippe

1980-01-01

Through a certain number of procedures, the thorough appreciation of the safety of a nuclear installation relies more on a specific appreciation taking into account the references as a whole, than on a technical regulation which claims to cover all the problems. Nevertheless, a French technical regulation structure regarding the safety domain must be built up progressively. The authors consider the principles of such a structure, and together they make the inventory of the works, finished, in progress or contemplated. The description of this specifically French approach emphazises the multiple and complementary forms given to statutory implements [fr

Interleukin 8 in progression of hormone-dependent early breast cancer

Indian Academy of Sciences (India)

The only way to perceive the real clinical course of disease and the prognostic significance of potential biomarkers is follow-up of patients who did not receive any kind of adjuvant therapy. Many studies have confirmed high levels ofinterleukin 8 (IL8) in HER2-enriched and basal-like (ER–) primary breast tumours, but less is ...

Differential expression of follistatin and FLRG in human breast proliferative disorders

Directory of Open Access Journals (Sweden)

Amaral Vania F

2009-09-01

Full Text Available Abstract Background Activins are growth factors acting on cell growth and differentiation. Activins are expressed in high grade breast tumors and they display an antiproliferative effect inducing G0/G1 cell cycle arrest in breast cancer cell lines. Follistatin and follistatin- related gene (FLRG bind and neutralize activins. In order to establish if these activin binding proteins are involved in breast tumor progression, the present study evaluated follistatin and FLRG pattern of mRNA and protein expression in normal human breast tissue and in different breast proliferative diseases. Methods Paraffin embedded specimens of normal breast (NB - n = 8; florid hyperplasia without atypia (FH - n = 17; fibroadenoma (FIB - n = 17; ductal carcinoma in situ (DCIS - n = 10 and infiltrating ductal carcinoma (IDC - n = 15 were processed for follistatin and FLRG immunohistochemistry and in situ hybridization. The area and intensity of chromogen epithelial and stromal staining were analyzed semi-quantitatively. Results Follistatin and FLRG were expressed both in normal tissue and in all the breast diseases investigated. Follistatin staining was detected in the epithelial cytoplasm and nucleus in normal, benign and malignant breast tissue, with a stronger staining intensity in the peri-alveolar stromal cells of FIB at both mRNA and protein levels. Conversely, FLRG area and intensity of mRNA and protein staining were higher both in the cytoplasm and in the nucleus of IDC epithelial cells when compared to NB, while no significant changes in the stromal intensity were observed in all the proliferative diseases analyzed. Conclusion The present findings suggest a role for follistatin in breast benign disease, particularly in FIB, where its expression was increased in stromal cells. The up regulation of FLRG in IDC suggests a role for this protein in the progression of breast malignancy. As activin displays an anti-proliferative effect in human mammary cells, the

Study Manual for breast imaging for radiology residents

International Nuclear Information System (INIS)

Ramirez Benavides, Rebeca

2010-01-01

Breast cancer is a disease that affects women worldwide. This cancer has become a public health problem, currently holding the first incidence and mortality from neoplasms in women of Costa Rica. That's why early detection makes it so important, so you should educate patients about the importance of annual mammograms, regular breast self-examination and consult immediately with the appearance of any abnormality in the breast. Mammography has been the only continuous proven method of screening for breast cancer. However, breast ultrasound is a valuable and effective tool for the evaluation and diagnosis of breast disease. The country lacks a picture book in the breast that fits entirely on the conditions of post-degree program, be practical and use the own methodology of the health system; therefore, the objective of this research is to organize a manual with the review of recent literature on the radiologic evaluation of the breast, with guidance on the methodology and the own resources of the country. This manual aims to provide a guide or basis for the radiologist in training, the important task of obtaining the knowledge, skill and ability to meet the enormous responsibility to participate in early detection of breast cancer. It also may help prevent the development and progression of the dreaded breast cancer in patients during their subsequent professional performance. (author) [es

Clinical radiology of the breast

International Nuclear Information System (INIS)

Roebuck, E.J.; Blamey, R.W.

1990-01-01

This book reports on the diagnosis and management of breast cancer from a surgical perspective, is a dissertation about mammography. The intent of the author was not to provide a definitive treatise on the subject, but rather to supplement information already implied in certain of the excellent existing tests. The author has therefore included more historical detail, statistics, and technical aspects of mammography than usually found in other monographs

Breast cancer. Current approach in the treatment

International Nuclear Information System (INIS)

Hernandez Menendez, Miguel M; Chaparro Cuellar, Sixta Rossana

2009-01-01

Of 115 women who had surgery for a malignant breast tumor proven by biopsy at the Department of General Surgery, Hospital 'Jose Ramon Lopez Tabrane' of Matanzas during the period January 2007 to May 2008 a study was conducted observational, analytical (study cohort) and using certain variables, with the aim of analyzing the behavior of this disease in our environment. Data were collected from medical records of patients admitted a breast lump in that period and files Statistics and Provincial Hospital Pathology 'Jose Ramon Lopez Tabrane'. The percentage method was applied to the description found in our sample, expressing the results in tabular form, with the objective facilitate their interpretation. The most affected age range between 65 and 74, but followed very near the range between 55 and 64. The most frequent clinical stage II, followed by the III. The left breast has proven to be most affected in outer quadrant exceeded. Veronesi conservative technique was the most used in our study. We recommend promoting breast self-examination and use of media We recommend promoting breast self-examination and use of media such as mammography as a method of early diagnosis of breast cancer and the creation of a file to the technical assessment conservative based on the survival and the immediate and mediate complications of this technique, and the best instruction in family practice clinical diagnosis of breast diseases and specialized inter consultation. (Author)

From Community Laywomen to Breast Health Workers: A Pilot Training Model to Implement Clinical Breast Exam Screening in Malawi.

Directory of Open Access Journals (Sweden)

Lily Gutnik

Full Text Available Breast cancer burden is high in low-income countries. Inadequate early detection contributes to late diagnosis and increased mortality. We describe the training program for Malawi's first clinical breast exam (CBE screening effort.Laywomen were recruited as Breast Health Workers (BHWs with the help of local staff and breast cancer advocates. The four-week training consisted of lectures, online modules, role-playing, case discussions, CBE using simulators and patients, and practice presentations. Ministry of Health trainers taught health communication, promotion, and education skills. Breast cancer survivors shared their experiences. Clinicians taught breast cancer epidemiology, prevention, detection, and clinical care. Clinicians and research staff taught research ethics, informed consent, data collection, and professionalism. Breast cancer knowledge was measured using pre- and post-training surveys. Concordance between BHW and clinician CBE was assessed. Breast cancer talks by BHW were evaluated on a 5-point scale in 22 areas by 3 judges.We interviewed 12 women, and 4 were selected as BHWs including 1 breast cancer survivor. Training was dynamic with modification based on trainee response and progress. A higher-than-anticipated level of comprehension and interest led to inclusion of additional topics like breast reconstruction. Pre-training knowledge increased from 49% to 91% correct (p<0.0001. Clinician and BHW CBE had 88% concordance (kappa 0.43. The mean rating of BHW educational talks was 4.4 (standard deviation 0.7.Malawian laywomen successfully completed training and demonstrated competency to conduct CBE and deliver breast cancer educational talks. Knowledge increased after training, and concordance was high between BHW and clinician CBE.

Consultant breast radiographers: Where are we now?

International Nuclear Information System (INIS)

Rees, Zebby

2014-01-01

Introduction: The aim of this study is to: • Evaluate the current role of the consultant breast radiographer. • Compare current practice with the four key components for consultant practice. • Gauge the support of radiologist colleagues. • Determine the other professional commitments involved with the role. This study could be the precursor for a macro study of all consultant radiographer practice in other specialities. Methodology: Methodology used was a comparative ethnographic study. Questionnaires to the 24 consultant breast radiographers currently in post, and consultant breast radiologists, who work with them, were conducted. Data collection was a qualitative thematic approach. Conclusion: Consultant breast radiographers provide high quality care to patients through excellent clinical practice, leadership and good communication. However, this study shows hospital Trusts emphasis for non medical consultants is for clinical practice first. Some radiologists are still a barrier to progression for consultant breast radiographers, and radiologists have a big influence in recruitment decisions. Consultant breast radiographer posts are well established, their numbers are increasing through recognition of the role and of their abilities and performance. Consultant breast radiographers state that becoming a consultant is the major achievement of their career, proving the Society of Radiographers' vision of the four-tier career structure has been well received by the radiography profession

[Fibromyalgia syndrome after comprehensive treatment of breast cancer: a case report].

Science.gov (United States)

Ding, Xia; Li, Yan; Cui, Yiyi; Shen, Yingying; Gu, Jianzhong; Guo, Yong

2016-05-25

Fibromyalgia syndrome after comprehensive treatment of breast cancer is rare and seldom reported. Here we present a case of a 50-year-old female patient,who was admitted to the hospital because of generalized fibromyalgia for 3 months and brain metastasis after the right breast carcinoma surgery for 1 month, and the clinical diagnosis was brain metastasis from breast carcinoma combined with fibromyalgia syndrome. The fibromyalgia were relieved with proper symptomatic treatment but the patient eventually died of tumor progression.

Missed breast carcinoma; why and how to avoid?

International Nuclear Information System (INIS)

Kamal, R.; Abdel Razek, N.M.; Hassan, M.A.; Shaalan, M.A.

2007-01-01

Despite the advances in mammography techniques, it still has a number of limitations. It is estimated that about 10 to 25% of lesions are overlooked in mammograms out of which about two thirds are detected retrospectively by radiologists and oncologists. Causes of missed breast cancer on mammography can be secondary to many factors including those related to the patient (whether inherent or acquired), the nature of the malignant mass itself, poor mammographic techniques, provider factors or interpretive skills of radiologists and oncologists (including perception and interpretation errors). Aim of Work: The aim of this study is to investigate the aforementioned factors hindering early breast cancer detection and in turn lowering mammographic sensitivity and to outline the major guidelines to overcome these factors aiming to an optimum mammographic examination and interpretation by radiologists and oncologists. Subject and Methods: We conducted this multicenter study over a two-year interval. We included 152 histo-pathological proven breast carcinomas that were initially missed on mammography. The cases were subjected to mammography, complementary US, MRI and digital mammography in some cases and all cases were histo-pathologically proven either by FNAB, CNB or open biopsy. Results: Revision of the pathological specimens of these 152 cases revealed 121 infiltrating ductal carcinomas, 2 lobular, 4 mucinous, 14 inflammatory carcinomas, 6 carcinomas in situ (3 of which were intracystic), 2 intraductal papillary carcinomas and 3 cases with Paget's disease of the nipple. In analyzing the causes responsible for misdiagnosis of these carcinomas we classified them into 4 causative factors; patient, tumor, technical or provider factors. Tumor factors were the most commonly encountered, accounting for 44. I %, while provider factors were the least commonly encountered in 14.5%. Carcino- mas were detected using several individual or combined complementary techniques. These

MR imaging of the breast

International Nuclear Information System (INIS)

Kaiser, W.A.

1989-01-01

Among a total of 361 MR breast examinations made since March 1984, there were 205 dynamic gradient-echo sequences after injection of Gd-DTPA (0.1 mM/kg). Of 38 histologically proved carcinomas, 37 showed a sudden increase of signal intensity of > 90% within the first minutes after the injection and nearly a plateau level afterwards. Benign lesions showed a lower, slower, and progressive increase. One 6-mm carcinoma was not detected, and one fibroadenoma was misdiagnosed as a carcinoma. The author discusses a standardized examination technique is essential (infusion technique, injection place, stretched arm, section selection, transmitter and receiver adjustment, storage reservation, phase encoding direction, double breast coil, etc.)

Neoadjuvant letrozole for postmenopausal estrogen receptor-positive, HER2-negative breast cancer patients, a study from the Danish Breast Cancer Cooperative Group (DBCG)

DEFF Research Database (Denmark)

Skriver, Signe Korsgaard; Laenkholm, Anne-Vibeke; Rasmussen, Birgitte Bruun

2018-01-01

response and 55% of patients had partial pathological response. ER at 100%, ductal subtype, tumor size below 2 cm and lymph node-negative status was significantly associated with a better response to NET and malignancy grade 3 with a poorer response to NET. One patient progressed during treatment......INTRODUCTION: Neoadjuvant endocrine treatment (NET) is a low-toxicity approach to achieve operability in locally advanced breast cancer, and to facilitate breast conservation in early breast cancer, particular in patients with highly estrogen receptor (ER) positive and HER2-negative disease. Here......, we report the results obtained by neoadjuvant letrozole in patients with early breast cancer in a phase-II design. MATERIAL AND METHODS: A total of 119 postmenopausal women with ER-positive, HER2-negative operable breast cancer were assigned to four months of neoadjuvant letrozole before definitive...

DNA/RNA-based formulations for treatment of breast cancer.

Science.gov (United States)

Xie, Zhaolu; Zeng, Xianghui

2017-12-01

To develop a successful formulation for the gene therapy of breast cancer, an effective therapeutic nucleic acid and a proper delivery system are essential. Increased understanding of breast cancer, and developments in biotechnology, material science and nanotechnology have provided a major impetus in the development of effective formulations for the gene therapy of breast cancer. Areas covered: We discuss DNA/RNA-based formulations that can inhibit the growth of breast cancer cells and control the progress of breast cancer. Targets for the gene therapy of breast cancer, DNA/RNA-based therapeutics and delivery systems are summarized. And examples of successful DNA/RNA-based formulations for breast cancer gene therapy are reviewed. Expert opinion: Several challenges remain in developing effective DNA/RNA-based formulations for treatment of breast cancer. Firstly, most of the currently utilized targets are not effective enough as monotherapy for breast cancer. Secondly, the requirements for co-delivery system make the preparation of formulation more complicated. Thirdly, nanoparticles with the modification of tumor-targeting ligands could be more unstable in circulation and normal tissues. Lastly, immune responses against the viral vectors are unfavorable for the gene therapy of breast cancer because of the damage to the host and the impaired therapeutic ability.

Non-technical constraints to eradication: the Italian experience.

Science.gov (United States)

Moda, Giuliana

2006-02-25

Although technical constraints to eradication of bovine tuberculosis are well-recognised, non-technical constraints can also delay progress towards eradication, leading to inefficiency and increased programme costs. This paper seeks to analyse the main non-technical constraints that can interfere with the successful implementation of tuberculosis eradication plans, based on experiences from an area of high tuberculosis prevalence in Regione Piemonte, Italy. The main social and economic constraints faced in the past 20 years are reviewed, including a social reluctance to recognise the importance of seeking eradication as the goal of disease control, effective communication of technical issues, the training and the organization of veterinary services, the relationship between the regional authority and farmers and their representatives, and data management and epidemiological reporting. The paper analyses and discusses the solutions that were applied in Regione Piemonte and the benefits that were obtained. Tuberculosis eradication plans are one of the most difficult tasks of the Veterinary Animal Health Services, and non-technical constraints must be considered when progress towards eradication is less than expected. Organizational and managerial resources can help to overcome social or economic obstacles, provided the veterinary profession is willing to address technical, but also non-technical, constraints to eradication.

Circumscribed Morphea and Breast Asymmetry in an Adolescent

Directory of Open Access Journals (Sweden)

António Augusto Fernandes Massa

2014-01-01

Full Text Available Morphea is a rare fibrosing disorder of the skin and underlying tissues. Circumscribed morphea presents with less than three discrete indurated plaques and breasts are commonly affected in women. We report the case of a 12-year-old female with a right infra-areolar, nontender, brownish patch and asymmetry of the right breast with 2 years of evolution. Skin biopsy showing thickening of the dermal collagen bundles confirmed the clinical diagnosis of morphea. After a 3-year follow-up period without progression of disease, reconstructive surgery is scheduled. Plaque morphea can involve all layers of the skin but associated breast deformity is rare. It can mimic benign and malignant breast disorders justifying the benefit for early tissue biopsy. Breast morphea generally has a good prognosis but hyperpigmentation and breast deformity in young girls have been rarely described. An early diagnosis can possibly lead to a therapeutic intervention with a different outcome, as it can be the source of severe psychological and social issues in a delicate period of development such as adolescence.

In search of a stem cell hierarchy in the human breast and its relevance to breast cancer evolution

DEFF Research Database (Denmark)

Villadsen, René

2005-01-01

. Most attention has been devoted to the question of different cellular origins of cancer subtypes and different susceptibilities of possible stem cells to gain or loss of oncogenes and tumor suppressor genes, respectively. Invaluable progress has been made over the past two decades in culture technology......, kidney and prostate. It is therefore now possible to integrate this information in a search for similar cells within the breast. Even if cell turnover after birth is provided exclusively by dividing lineage-restricted cells, more information about the robustness of breast differentiation programs during...

Early Dysregulation of Cell Adhesion and Extracellular Matrix Pathways in Breast Cancer Progression

Science.gov (United States)

Emery, Lyndsey A.; Tripathi, Anusri; King, Chialin; Kavanah, Maureen; Mendez, Jane; Stone, Michael D.; de las Morenas, Antonio; Sebastiani, Paola; Rosenberg, Carol L.

2009-01-01

Proliferative breast lesions, such as simple ductal hyperplasia (SH) and atypical ductal hyperplasia (ADH), are candidate precursors to ductal carcinoma in situ (DCIS) and invasive cancer. To better understand the relationship of breast lesions to more advanced disease, we used microdissection and DNA microarrays to profile the gene expression of patient-matched histologically normal (HN), ADH, and DCIS from 12 patients with estrogen receptor positive sporadic breast cancer. SH were profiled from a subset of cases. We found 837 differentially expressed genes between DCIS-HN and 447 between ADH-HN, with >90% of the ADH-HN genes also present among the DCIS-HN genes. Only 61 genes were identified between ADH-DCIS. Expression differences were reproduced in an independent cohort of patient-matched lesions by quantitative real-time PCR. Many breast cancer-related genes and pathways were dysregulated in ADH and maintained in DCIS. Particularly, cell adhesion and extracellular matrix interactions were overrepresented. Focal adhesion was the top pathway in each gene set. We conclude that ADH and DCIS share highly similar gene expression and are distinct from HN. In contrast, SH appear more similar to HN. These data provide genetic evidence that ADH (but not SH) are often precursors to cancer and suggest cancer-related genetic changes, particularly adhesion and extracellular matrix pathways, are dysregulated before invasion and even before malignancy is apparent. These findings could lead to novel risk stratification, prevention, and treatment approaches. PMID:19700746

TECHNICAL COORDINATION

CERN Multimedia

A. Ball and W. Zeuner

2011-01-01

In this report we will review the main achievements of the Technical Stop and the progress of several centrally-managed projects to support CMS operation and maintenance and prepare the way for upgrades. Overview of the extended Technical Stop  The principal objectives of the extended Technical Stop affecting the detector itself were the installation of the TOTEM T1 telescopes on both ends, the readjustment of the alignment link-disk in YE-2, the replacement of the light-guide sleeves for all PMs of both HFs, and some repairs on TOTEM T2 and CASTOR. The most significant tasks were, however, concentrated on the supporting infrastructure. A detailed line-by-line leak search was performed in the C6F14 cooling system of the Tracker, followed by the installation of variable-frequency drives on the pump motors of the SS1 and SS2 tracker cooling plants to reduce pressure transients during start-up. In the electrical system, larger harmonic filters were installed in ...

Assessment and Development of Microwave Imaging for Breast Cancer Detection

DEFF Research Database (Denmark)

Jensen, Peter Damsgaard

At the Technical University of Denmark (DTU), a 3D tomographic microwave imaging system is currently being developed with the aim of using nonlinear microwave imaging for breast-cancer detection. The imaging algorithm used in the system is based on an iterative Newton-type scheme. In this algorithm...... used in the microwave tomographic imaging system is presented. Non-linear microwave tomographic imaging of the breast is a challenging computational problem. The breast is heterogeneous and contains several high-contrast and lossy regions, resulting in large differences in the measured signal levels....... This implies that special care must be taken when the imaging problem is formulated. Under such conditions, microwave imaging systems will most often be considerably more sensitive to changes in the electromagnetic properties in certain regions of the breast. The result is that the parameters might...

Hornerin, an S100 family protein, is functional in breast cells and aberrantly expressed in breast cancer

International Nuclear Information System (INIS)

Fleming, Jodie M; Ginsburg, Erika; Oliver, Shannon D; Goldsmith, Paul; Vonderhaar, Barbara K

2012-01-01

Recent evidence suggests an emerging role for S100 protein in breast cancer and tumor progression. These ubiquitous proteins are involved in numerous normal and pathological cell functions including inflammatory and immune responses, Ca 2+ homeostasis, the dynamics of cytoskeleton constituents, as well as cell proliferation, differentiation, and death. Our previous proteomic analysis demonstrated the presence of hornerin, an S100 family member, in breast tissue and extracellular matrix. Hornerin has been reported in healthy skin as well as psoriatic and regenerating skin after wound healing, suggesting a role in inflammatory/immune response or proliferation. In the present study we investigated hornerin’s potential role in normal breast cells and breast cancer. The expression levels and localization of hornerin in human breast tissue, breast tumor biopsies, primary breast cells and breast cancer cell lines, as well as murine mammary tissue were measured via immunohistochemistry, western blot analysis and PCR. Antibodies were developed against the N- and C-terminus of the protein for detection of proteolytic fragments and their specific subcellular localization via fluorescent immunocytochemisty. Lastly, cells were treated with H 2 O 2 to detect changes in hornerin expression during induction of apoptosis/necrosis. Breast epithelial cells and stromal fibroblasts and macrophages express hornerin and show unique regulation of expression during distinct phases of mammary development. Furthermore, hornerin expression is decreased in invasive ductal carcinomas compared to invasive lobular carcinomas and less aggressive breast carcinoma phenotypes, and cellular expression of hornerin is altered during induction of apoptosis. Finally, we demonstrate the presence of post-translational fragments that display differential subcellular localization. Our data opens new possibilities for hornerin and its proteolytic fragments in the control of mammary cell function and breast

Hornerin, an S100 family protein, is functional in breast cells and aberrantly expressed in breast cancer

Directory of Open Access Journals (Sweden)

Fleming Jodie M

2012-06-01

Full Text Available Abstract Background Recent evidence suggests an emerging role for S100 protein in breast cancer and tumor progression. These ubiquitous proteins are involved in numerous normal and pathological cell functions including inflammatory and immune responses, Ca2+ homeostasis, the dynamics of cytoskeleton constituents, as well as cell proliferation, differentiation, and death. Our previous proteomic analysis demonstrated the presence of hornerin, an S100 family member, in breast tissue and extracellular matrix. Hornerin has been reported in healthy skin as well as psoriatic and regenerating skin after wound healing, suggesting a role in inflammatory/immune response or proliferation. In the present study we investigated hornerin’s potential role in normal breast cells and breast cancer. Methods The expression levels and localization of hornerin in human breast tissue, breast tumor biopsies, primary breast cells and breast cancer cell lines, as well as murine mammary tissue were measured via immunohistochemistry, western blot analysis and PCR. Antibodies were developed against the N- and C-terminus of the protein for detection of proteolytic fragments and their specific subcellular localization via fluorescent immunocytochemisty. Lastly, cells were treated with H2O2 to detect changes in hornerin expression during induction of apoptosis/necrosis. Results Breast epithelial cells and stromal fibroblasts and macrophages express hornerin and show unique regulation of expression during distinct phases of mammary development. Furthermore, hornerin expression is decreased in invasive ductal carcinomas compared to invasive lobular carcinomas and less aggressive breast carcinoma phenotypes, and cellular expression of hornerin is altered during induction of apoptosis. Finally, we demonstrate the presence of post-translational fragments that display differential subcellular localization. Conclusions Our data opens new possibilities for hornerin and its

Effects of humic substances on the migration of radionuclides: complexation and transport of actinides. First technical progress report (work period 01.97 - 12.97)

International Nuclear Information System (INIS)

Buckau, G.

1998-08-01

The present report describes progress within the first year of the EC-project 'Effects of Humic Substances on the Migration of Radionuclides: Complexation and Transport of Actinides'. The project is conducted within the EC-Cluster 'Radionuclide Transport/Retardation Processes'. Contrary to formal requirements of the Commission, this report with a great deal of detail is established already after one year of project work. It is scheduled to be followed by a second technical progress report covering the second year of the project. In agreement with the contractual obligations a final report of similar technical detail will also be generated. The report contains an executive summary written by the coordinator (FZK/INE) with strong support from the other three task leaders (BGS, CEA-SGC and RMC-E). More detailed results are given by individual contributions of the project partners in 13 annexes. In the executive summary report the origin of results presented is given, also serving as guidance for finding more detailed results in the annexes. Not all results are discussed or referred to in the executive summary report and thus readers with a deeper interest also need to consult the annexes. (orig.)

Percutaneous cryoablation of liver metastases from breast cancer: Initial experience in 17 patients

International Nuclear Information System (INIS)

Zhang, W.; Yu, H.; Guo, Z.; Li, B.; Si, T.; Yang, X.; Wang, H.

2014-01-01

Aim: To assess the feasibility, safety, and effectiveness of percutaneous cryoablation for the treatment of liver metastases from breast cancer. Materials and methods: This study included 39 liver metastases in 17 female breast cancer patients who underwent computed tomography (CT)-guided percutaneous cryoablation. The mean age of the cohort was 55 years (range 30–66 years). The tumour response was evaluated by CT performed before treatment, 1 month after treatment, and every 3 months thereafter. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) was used to assess the patients' quality of life before, 1 week, 1 month, and 3 months after cryoablation. The primary endpoints were technique effectiveness, quality of life, and complications. Results: The technical success rate was 92% with no major complication reported. At the 1-month follow-up, the primary technique effectiveness was 87.1% (34 of 39 tumours). At the 3-months follow-up, local tumour progression was observed in six of 39 lesions (15.4%). The 1-year survival from the time of cryoablation was 70.6%. The quality of life symptoms and functioning scales were preserved in patients alive at 3 months after cryoablation. The global quality of life, mean value of “pain” and “fatigue” between 3 months after cryoablation and prior to treatment showed statistically significant differences, but no clinical significance. Conclusions: Cryoablation is a safe and effective ablative therapy, providing a high rate of local tumour control in breast cancer liver metastases

Resolving breast cancer heterogeneity by searching reliable protein cancer biomarkers in the breast fluid secretome

International Nuclear Information System (INIS)

Mannello, Ferdinando; Ligi, Daniela

2013-01-01

One of the major goals in cancer research is to find and evaluate the early presence of biomarkers in human fluids and tissues. To resolve the complex cell heterogeneity of a tumor mass, it will be useful to characterize the intricate biomolecular composition of tumor microenvironment (the so called cancer secretome), validating secreted proteins as early biomarkers of cancer initiation and progression. This approach is not broadly applicable because of the paucity of well validated and FDA-approved biomarkers and because most of the candidate biomarkers are mainly organ-specific rather than tumor-specific. For these reasons, there is an urgent need to identify and validate a panel of biomarker combinations for early detection of human tumors. This is especially important for breast cancer, the cancer spread most worldwide among women. It is well known that patients with early diagnosed breast cancer live longer, require less extensive treatment and fare better than patients with more aggressive and/or advanced disease. In the frame of searching breast cancer biomarkers (especially using nipple aspirate fluid mirroring breast microenvironment), studies have highlighted an optimal combination of well-known biomarkers: uPA + PAI-1 + TF. When individually investigated they did not show perfect accuracy in predicting the presence of breast cancer, whereas the triple combination has been demonstrated to be highly predictive of pre-cancer and/or cancerous conditions, approaching 97-100% accuracy. Despite the heterogeneous composition of breast cancer and the difficulties to find specific breast cancer biomolecules, the noninvasive analysis of the nipple aspirate fluid secretome may significantly improve the discovery of promising biomarkers, helping also the differentiation among benign and invasive breast diseases, opening new frontiers in early oncoproteomics

Assessment of the breast volume by a new simple formula

Directory of Open Access Journals (Sweden)

El-Oteify Mahmoud

2006-01-01

Full Text Available Background: With the recent introduction of improved techniques for plastic surgery of the breast and increased public awareness toward these procedures, plastic surgeons are continuously trying to improve their methods and results to reach perfection. Assessment of the breast volume is an important issue prior to the use of breast implants in any aesthetic or reconstructive breast surgery. Previous methods to measure breast volume have included use of a simple bra and breast cup size, cumbersome fluid displacement, appliances and approximate visual estimation. Objectives: In this work we have tried to develop an easy method for assessment of the breast volume for both the patient and the the surgeon through a simple mathematical formula. Materials and Methods: Fifty two volunteers were included in this study. For every one, general parameters including age, weight and height were recorded. Local breast measurements and water volume displacement were also recorded. Results: The collected data were statistically correlated. Using the analyzed data, the breast volume was calculated through a simple and direct formula on the basis of the breast circumference. Conclusion: Our method has, as its principle, the use of an accurate and simple formula, which is based only on one measurement. This is easy for both the patient and the plastic surgeon. This equation is not only a significant technical advantage for the surgeon, but also provides a universal standardization of the breast volume.

Impact of palbociclib combinations on treatment of advanced estrogen receptor-positive/human epidermal growth factor 2-negative breast cancer

Directory of Open Access Journals (Sweden)

Boér K

2016-10-01

Full Text Available Katalin Boér Department of Medical Oncology, Szent Margit Hospital, Budapest, Hungary Abstract: Breast cancer is a heterogeneous disease with multiple subgroups based on clinical and molecular characteristics. For the largest subgroup of breast cancers, hormone receptor-positive/human epidermal growth factor 2 (HER2-negative tumors, hormone treatment is the mainstay of therapy and is likely to result in significant improvement in disease outcomes. However, some of these cancers demonstrate de novo or acquired resistance to endocrine therapy. Despite intensive research to develop new strategies to enhance the efficacy of currently available treatment options for hormone receptor-positive breast cancer, progress has been slow, and there were few advances for a period of 10 years. In 2012, a new molecularly targeted therapeutic strategy, inhibition of mammalian target of rapamycin with everolimus, was introduced into clinical practice. Everolimus, in combination with a steroidal aromatase inhibitor, exemestane, resulted in an increase in progression-free survival, but not overall survival in patients with estrogen receptor (ER+ve advanced disease who had progressed on hormone therapy. In 2015, the first cyclin-dependent kinases 4/6 (CDK4/6 inhibitor, palbociclib, received accelerated US Food and Drug Administration approval for use in combination with letrozole for the treatment of postmenopausal ER+ve/HER2-ve advanced breast cancer as initial, endocrine-based therapy. The addition of palbociclib to endocrine therapy resulted in longer progression-free survival than letrozole alone. One year later, palbociclib received a new indication, use in combination with fulvestrant, in both premenopausal and postmenopausal females with advanced breast cancer of the same subtype with disease progression following endocrine therapy. Adding palbociclib to fulvestrant resulted in a significantly increased median progression-free survival compared to fulvestrant

Radiotherapy effect in conservation treatment for breast cancer

International Nuclear Information System (INIS)

Sachini, V.; Ferreri, A.J.M.; Farante, G.; Agresti, R.; Galimberti, V.; Zurrida, S.; Veronesi, P.

1994-01-01

Radiotherapy (RT) in conservative treatment for breast cancer (CT-BC) has been proven to be determinant for the local control of the disease. Radiation therapy was described by several authors as the most important factor affecting the cosmetic results of this treatment. Technical progress in RT, use of filters and wedges and an increased knowledge of the influence of fraction size total dose and irradiated volume on breast tissues contributed to avoid major radiotherapeutic side effects in the CT-BC. Cosmetic outcome from 2 groups of patients (pts) with breast cancer in stage T 1-2(T> = 2,5 cm) N 0-1 M o0 of the prospective trial Milan III were compared. Both groups pts (n=89) were treated with quadrantectomyand axillary dissection. 49 pts received complementary RT with a dose of 50 Gy over 5 weeks with a daily fraction of 2 Gy and a further boost of 10 Gy (10 MeV electrons) on the scar. Remaining 40 pts did not receive RT. Cosmetic results were subjectively and objectively (asymmetry index) evaluated. No significant cosmetic differences were observed between the 2 study groups. A good or excellent symmetry was observed in 59% of irradiated pts and 64% of non irradiated pts. Negative results were observed in 4% and 2% respectively. Subjective ovulation showed similar results, with a good or excellent symmetry in 57% of irradiated pts and 72.5% of non irradiated pts. Poor results were observed in 16.3% and 27.5% respectively. Telangiectasia were observed in 4% of irradiated pts, while hypertrophied scars were only noted in non irradiated pts (15%). No acute side effects of RT, as erythema or ulceration of breast skin, were recorded. In our experience, the standard dose of 50 Gy administered by two opposite tangential fields plus a 10 Gy boost did not affect the cosmetic results of CT.BC, whereas it provided a better local control of disease. The possibility to avoid RT in selected group of pts should be justified by the discomfort of this treatment for the pt, cost

Nuclear osteopontin-c is a prognostic breast cancer marker.

Science.gov (United States)

Zduniak, K; Ziolkowski, P; Ahlin, C; Agrawal, A; Agrawal, S; Blomqvist, C; Fjällskog, M-L; Weber, G F

2015-02-17

Although Osteopontin has been known as a marker for cancer progression, the elevated production of this cytokine is not specific for cancer. We have identified the splice variant Osteopontin-c as being absent from healthy tissue but associated with about 75% of breast cancer cases. However, in previous studies of Osteopontin-c, follow-up information was not available. Here we have analysed 671 patients, comprising a cohort of 291 paraffin blocks plus a population-based case-control study of 380 arrayed breast tumor tissues. We find that high staining intensity of nuclear Osteopontin-c is strongly associated with mortality in patients with early breast cancer. Cytosolic staining for exon 4, reflective of Osteopontin-a and -b also predicts poor outcome. By contrast, total Osteopontin does not correlate with prognosis. These diverse assessments of Osteopontin also do not correlate with each other, suggesting distinct expression patterns for the variant forms. Consistent with its role in tumor progression, not tumor initiation, Osteopontin-c is not correlated with proliferation markers (Ki-67, cyclin A, cyclin B, cyclin E and cyclin D), neither is it correlated with ER, PR or HER2. The addition of Osteopontin-c immunohistochemistry to standard pathology work-ups may have prognostic benefit in early breast cancer diagnosis.

Break Breast Cancer Addiction by CRISPR/Cas9 Genome Editing.

Science.gov (United States)

Yang, Haitao; Jaeger, MariaLynn; Walker, Averi; Wei, Daniel; Leiker, Katie; Weitao, Tao

2018-01-01

Breast cancer is the leading diagnosed cancer for women globally. Evolution of breast cancer in tumorigenesis, metastasis and treatment resistance appears to be driven by the aberrant gene expression and protein degradation encoded by the cancer genomes. The uncontrolled cancer growth relies on these cellular events, thus constituting the cancerous programs and rendering the addiction towards them. These programs are likely the potential anticancer biomarkers for Personalized Medicine of breast cancer. This review intends to delineate the impact of the CRSPR/Cas-mediated genome editing in identification and validation of these anticancer biomarkers. It reviews the progress in three aspects of CRISPR/Cas9-mediated editing of the breast cancer genomes: Somatic genome editing, transcription and protein degradation addictions.

Histone Methylation and Epigenetic Silencing in Breast Cancer

National Research Council Canada - National Science Library

Simon, Jeffrey A; Lange, Carol A

2008-01-01

.... EZH2 is a histone methyltransferase which modifies lysine-27 of histone H3 an epigenetic mark which is generally linked to gene silencing and is implicated in tumor suppressor silencing during breast cancer progression...

Epigenetic suppression of neprilysin regulates breast cancer invasion.

Science.gov (United States)

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

2016-03-07

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

Is progression-free survival a more relevant endpoint than overall survival in first-line HR+/HER2− metastatic breast cancer?

Directory of Open Access Journals (Sweden)

Forsythe A

2018-05-01

Full Text Available Anna Forsythe,1 David Chandiwana,2 Janina Barth,3 Marroon Thabane,4 Johan Baeck,5 Anastasiya Shor,1 Gabriel Tremblay6 1Health Technology Assessment Evidence, Purple Squirrel Economics, New York, NY, USA; 2Global Value and Access, Novartis Pharmaceutical Corporation, East Hanover, NJ, USA; 3German Market Access, Novartis Pharma GmbH, Nuremberg, Germany; 4Health Policy and Patient Access, Novartis Pharmaceuticals Incorporated, Dorval, QC, Canada; 5Global Medical Affairs (Oncology Business Unit, Novartis Pharmaceutical Corporation, East Hanover, NJ, USA; 6Health Economics, Purple Squirrel Economics, New York, NY, USA Background: Hormone receptor-positive (HR+, human epidermal growth factor receptor 2- negative (HER2−, metastatic breast cancer (MBC accounts for 73% of all MBCs. Endocrine therapy (ET is the basis of first-line (1L therapy for patients with HR+/HER2− MBC. Novel therapies have demonstrated improvements in progression-free survival (PFS compared to ET. The clinical relevance of PFS is being debated, as there is no proven direct correlation with overall survival (OS benefit to date. We reviewed studies of HR+/HER2− MBC to assess PFS and other factors that influence OS and treatment response, and health-related quality of life (HRQoL. Methods: The Embase®, Medline®, and Cochrane databases were systematically searched to identify studies in adult women with HR+/HER2− MBC, published between January 2006 and January 2017, and written in English. Phase II and III randomized controlled trials (RCTs, observational, and retrospective studies were included. Results: Seventy-nine RCTs were identified: 58 (73% in the 1L+ setting and 21 (27% in second-line or greater settings. PFS hazard ratios (HRs were reported in 61 (77% studies; 31 (39% reported significant PFS improvements. OS was reported in 44 (41% studies; 12 (15% reported significant OS improvements. Significant improvements in both PFS and OS were reported in only 6 (8% studies

Breast cancer diagnosis using FT-RAMAN spectroscopy

Science.gov (United States)

Bitar, Renata A.; Martin, Airton A.; Criollo, Carlos J. T.; Ramalho, Leandra N. Z.

2005-04-01

In this study FT-RAMAN spectra of breast tissue from 35 patients were obtained and separated into nine groups for histopathologic analysis, which are as follows: normal breast tissue, fibrocystic condition, in situ ductal carcinoma, in situ ductal carcinoma with necrosis, infiltrate ductal carcinoma, infiltrate inflammatory ductal carcinoma, infiltrate medullar ductal carcinoma, infiltrate colloid ductal carcinoma, and infiltrate lobular carcinoma. Using spectrum averages taken from each group a qualitative analysis was performed to compare these molecular compositions to those known to be present in abnormal concentrations in pathological situations, e.g. the development of desmoplastic lesions with a stroma of dense collagen in tumoral breast tissues which substitute adipose stroma of non-diseased breast tissue. The band identified as amino acids, offered basis for observation in the existence of alterations in the proteins, thus proving Raman Spectroscopic capacity in identification of primary structures of proteins; secondary protein structure was also identified through the peptic links, Amide I and Amide III, which have also been identified by various authors. Alterations were also identified in the peaks and bandwidths of nucleic acids demonstrating the utilization of Raman Spectroscopy in the analysis of the cells nucleus manifestations. All studies involving Raman Spectroscopy and breast cancer have shown excellent result reliability and therefore a basis for the technical theory.

A Community-Oriented Approach to Breast Cancer in a Low-Resource Setting: Improving Awareness, Early Detection and Treatment of Breast Cancer in Tajikistan.

Science.gov (United States)

Talib, Zohray; Shukurbekova, Irina; Sadonshoeva, Guldarbogh; Alibekov, Alibek; Jamshedov, Nekruz; Moloo, Zahir; Welji, Almas; Amersi, Farin; Muhammad, Aliya Amin; Jiwani, Aliya; Rais, Sheliza; Nazrishoeva, Akoyat; Ilnazarova, Surayo; Nuridinova, Shifo; Ukani, Hafiza; Alwani, Shireen; Saleh, Mansoor

2016-05-01

Breast cancer is one of the most common cancers and causes of death in females in Tajikistan; yet less than half of the adult women in Tajikistan have heard of breast cancer. Limited access to health care contributes to late stage presentation. We developed a public-private partnership to implement a breast cancer awareness intervention in a low-resource community in Khorog, Tajikistan. We trained local health professionals in clinical breast care and conducted a breast cancer screening and treatment program. The partnership involved visiting USA-based health professionals working alongside local health care providers (HCP) in the continuum of breast care-from education to the diagnostic evaluation and management of detected breast abnormalities. Patient data were collected using a web-based program (VirtualDoc). Twenty-four HCP received didactic and clinical breast examination training. 441 women underwent clinical breast evaluation. 74 (17%) had abnormal exams and underwent additional diagnostic procedures. We identified six (1.4%) cases of breast cancer (all locally advanced) and two women had benign fibroadenomas. All women with cancer underwent modified radical mastectomy, while the fibroadenomas were treated by cosmetically appropriate lumpectomy. Five of six subjects with cancer were previously aware of their breast lump and three had recently seen a family medicine (FM) doctor. Health systems assessment revealed availability of diagnostic equipment but lack of well-trained operators and clinician interpreters. We were successful in integrating clinical breast exams into the routine care of female patients by local FM doctors and in the process, achieved a better understanding of existing risk factors and barriers to breast cancer care. This public-private partnership, leveraging the technical expertise of visiting health professionals, demonstrates how a focused onsite training and awareness program can provide sustained improvements in breast care in a low

Pulsed Dose Rate (PDR - BT) brachytherapy in treatment of breast cancer

International Nuclear Information System (INIS)

Skowronek, J.

2007-01-01

Breast conserving surgery (BCS) and radiotherapy (EBRT) of the conserved breast became widely accepted in the last decades for the treatment of early invasive breast cancer. The standard technique of RT after breast conservation is to treat the whole breast up to a total dose of 45 to 50 Gy. Initially brachytherapy for breast cancer was used in addition of external radiation to boost a portion of the breast to higher doses. However, over the past 10 years, the application of brachytherapy in breast cancer has changed. In early stage breast cancer, research has shown that the area that requires radiation treatment to prevent the cancer from returning is the breast tissue that surrounds the area where the initial cancer was removed. Because this typically includes only a part of the breast, brachytherapy is now being used to treat the targeted portion of the breast and as a result allows accelerated delivery of the radiation dose so that treatment is completed in four to five days. Another indications for PDR - BT as a part of treatment in locally advanced breast cancer or as a palliative treatment are discussed in the paper, too. Preliminary results with PDR - BT boost technique are promising. However, more experience and longer follow-up are required to define whether these methods might improve local tumor control for breast cancer patients. In this article the current status, indications, technical aspects and published results of PDR brachytherapy (PDR - BT) in breast cancer treatment are reviewed. (author)

Host microenvironment in breast cancer development: Epithelial–mesenchymal transition in breast cancer development

International Nuclear Information System (INIS)

Vincent-Salomon, Anne; Thiery, Jean Paul

2003-01-01

The epithelial–mesenchymal transition (EMT) is a developmental mechanism of crucial importance in establishing the body plan in many multicellular organisms. Several transduction pathways controlling the various steps of the morphological transition have been identified by molecular analyses of this process in cell lines and in vivo. The newly formed mesenchymal cells can exhibit locomotory and invasive phenotypes, suggesting that EMTs contribute to the progression of carcinoma. Diverse evidence indicates that EMT subprograms are involved in the appearance of different breast carcinoma types. Several normal and malignant breast cell lines are currently being analyzed to define key steps in EMT and to identify candidate genes. DNA profiling technology is also being applied to uncover pathways that lead to a metastatic phenotype

Radiolesions after radiotherapy of breast cancer

International Nuclear Information System (INIS)

Abbatucci, J.S.

1975-01-01

A study is presented of the late radiolesions which occur after breast cancer irradiation. These lesions are described and the etiological factors are studied, with special emphasis given to the effect of dose and time factors. For the large volume considered in the irradiation of breast cancers, the tolerance dose for normal tissue (skin and connective subcutaneous tissue) can be set at 1,700 rets, that is, 5,600 rads in 28 sessions of 200 rads over a period of 38 days. Technical irradiation problems are given special mention as they can be the cause of dosimetric errors resulting in complications. Dosimetry should be in the whole volume, and not only in a single plane, as is still most often the case [fr

Radiolesions after radiotherapy of breast cancer

Energy Technology Data Exchange (ETDEWEB)

Abbatucci, J S [Centre Regional de Lutte contre le Cancer, 14 - Caen (France)

1975-11-01

A study is presented of the late radiolesions which occur after breast cancer irradiation. These lesions are described and the etiological factors are studied, with special emphasis given to the effect of dose and time factors. For the large volume considered in the irradiation of breast cancers, the tolerance dose for normal tissue (skin and connective subcutaneous tissue) can be set at 1,700 rets, that is, 5,600 rads in 28 sessions of 200 rads over a period of 38 days. Technical irradiation problems are given special mention as they can be the cause of dosimetric errors resulting in complications. Dosimetry should be in the whole volume, and not only in a single plane, as is still most often the case.

Association between poor clinical prognosis and sleep duration among breast cancer patients

Directory of Open Access Journals (Sweden)

Thalyta Cristina Mansano-Schlosser

Full Text Available ABSTRACT Objective: to investigate the association between clinical progression and the quality and duration of sleep in women with breast cancer. Method: longitudinal study, with 114 participants, conducted in a hospital in Brazil. The instruments used were: questionnaire for sociodemographic and clinical characterization, Pittsburgh Sleep Quality Index; Beck Depression Inventory and Herth Hope Scale. Data were analyzed through descriptive statistics and survival analyses (outcome: poor clinical progression, using the Kaplan-Meier curve, Log-rank test and Cox proportional model. Results: a higher probability of poor clinical progression was verified in women with sleep durations of less than six hours or nine hours and over (p=.0173. Conclusion: the results suggest the importance of further studies that seek to verify whether the quantitative management of sleep disorders would have an impact on the progression of breast cancer. Women should be encouraged to report sleep problems to nurses.

Stem cells in the human breast

DEFF Research Database (Denmark)

Petersen, Ole William; Polyak, Kornelia

2010-01-01

The origins of the epithelial cells participating in the development, tissue homeostasis, and cancer of the human breast are poorly understood. However, emerging evidence suggests a role for adult tissue-specific stem cells in these processes. In a hierarchical manner, these generate the two main...... mammary cell lineages, producing an increasing number of cells with distinct properties. Understanding the biological characteristics of human breast stem cells and their progeny is crucial in attempts to compare the features of normal stem cells and cancer precursor cells and distinguish these from...... nonprecursor cells and cells from the bulk of a tumor. A historical overview of research on human breast stem cells in primary tissue and in culture reveals the progress that has been made in this area, whereas a focus on the cell-of-origin and reprogramming that occurs during neoplastic conversion provides...

Flame-broiled food, NAT2 acetylator phenotype, and breast cancer risk among women with benign breast disease.

Science.gov (United States)

Gallicchio, Lisa; McSorley, Meghan A; Newschaffer, Craig J; Thuita, Lucy W; Argani, Pedram; Hoffman, Sandra C; Helzlsouer, Kathy J

2006-09-01

The objective of this study was to examine the association between flame-broiled food consumption, a source of heterocyclic amine exposure, and the development of breast cancer among cohort of women with benign breast disease (BBD). The variation of the association by acetylation phenotype, as determined by the genotypes of selected N-acetyltransferase 2 (NAT2) enzymes, was also examined. Among participants in an ongoing cohort study, 1187 women reported having a breast biopsy for BBD and completed a food frequency questionnaire. NAT2 G857A, NAT2 T341C, and NAT2 G590A genotypes were determined using DNA extracted from blood specimens collected in 1989. Incident cases of breast cancer were identified through linkage of the cohort participants with the Washington County Cancer Registry and the Maryland State Cancer Registry. Follow-up for the BBD cohort began at study entry in 1989 and ended on April 28, 2003. Of the women in this study, 77 subsequently developed breast cancer. Results showed that, among rapid acetylators, flame-broiled food intake was associated with a statistically significant increase in the risk of breast cancer (odds ratio (OR) 2.62; 95% confidence interval (CI) 1.06, 6.46). No association was observed between flame-broiled food intake and breast cancer among slow acetylators (OR 0.75; 95% CI 0.39, 1.43). These findings suggest that flame-broiled food may be a modifiable risk factor for the progression of BBD to invasive breast cancer among women who have genotypes consistent with rapid acetylation.

Individual differences in emotional expressivity predict oxytocin responses to cortisol administration : Relevance to breast cancer?

NARCIS (Netherlands)

Tops, Mattie; van Peer, Jacobien M.; Korf, Jakob

Reduced emotional expression has been consistently related to susceptibility or fast progression of breast cancer. Breast cancer development and reduced emotional expression have both been related to rejection- and separation-related conditions. The neuropeptide oxytocin is low in response to

HER-2-positive metastatic breast cancer: new possibilities for therapy

Directory of Open Access Journals (Sweden)

E. V. Artamonova

2013-01-01

Full Text Available This article is devoted to modern approaches in HER-2-positive metastatic breast cancer therapy. Recently treatment algorithm for this type of cancer included trastuzumab plus cytostatic in first line, continuation of trastuzumab with another chemotherapy regimen in second line, further switch to lapatinib and eventual return to trastuzumab after progression. Nowadays our options are broader owing to new anti-HER-2 agents which are pertruzumab and T-DM1. Now the most effective therapy regimen in first line is double HER-2 blockade (trastuzumab + pertuzumab in combination with docetaxel. Benefit of new agent T-DM1 versus combination of lapatinib and capecitabin is proved in patients progressed on trastuzumab and taxanes. T-DM1 also showed high efficacy as salvage therapy in intensively pretreated patients with meta- static HER-2-positive breast cancer who progressed on taxanes, trastuzumab and lapatinib.

The use of high-dose-rate brachytherapy alone after lumpectomy in patients with early-stage breast cancer treated with breast-conserving therapy

International Nuclear Information System (INIS)

Baglan, Kathy L.; Martinez, Alvaro A.; Frazier, Robert C.; Kini, Vijay R.; Kestin, Larry L.; Chen, Peter Y.; Edmundson, Greg; Mele, Elizabeth; Jaffray, David; Vicini, Frank A.

2001-01-01

Purpose: We present the preliminary results of our in-house protocol using outpatient high-dose-rate (HDR) brachytherapy as the sole radiation modality following lumpectomy in patients with early-stage breast cancer. Methods and Materials: Thirty-seven patients with 38 Stage I-II breast cancers received radiation to the lumpectomy cavity alone using an HDR interstitial implant with 192 Ir. A minimum dose of 32 Gy was delivered on an outpatient basis in 8 fractions of 4 Gy to the lumpectomy cavity plus a 1- to 2-cm margin over consecutive 4 days. Results: Median follow-up is 31 months. There has been one ipsilateral breast recurrence for a crude failure rate of 2.6% and no regional or distant failures. Wound healing was not impaired in patients undergoing an open-cavity implant. Three minor breast infections occurred, and all resolved with oral antibiotics. The cosmetic outcome was good to excellent in all patients. Conclusion: In selected patients with early-stage breast cancer, treatment of the lumpectomy cavity alone with outpatient HDR brachytherapy is both technically feasible and well tolerated. Early results are encouraging, however, longer follow-up is necessary before equivalence to standard whole-breast irradiation can be established and to determine the most optimal radiation therapy technique to be employed

Bevacizumab in the treatment of five patients with breast cancer and brain metastases: Japan Breast Cancer Research Network-07 trial

Directory of Open Access Journals (Sweden)

Yamamoto D

2012-09-01

Full Text Available Daigo Yamamoto,1,3 Satoru Iwase,2 Yu Tsubota,1 Noriko Sueoka,1 Chizuko Yamamoto,3 Kaoru Kitamura,4 Hiroki Odagiri,5 Yoshinori Nagumo61Department of Surgery, Kansai Medical University, Hirakata, Osaka, 2Department of Palliative Medicine, University of Tokyo Hospital, Tokyo, 3Department of Internal Medicine, Seiko Hospital, Neyagawa, Osaka, 4Breast Unit, Nagumo Clinic, Fukuoka, 5Department of Surgery, Hirosaki National Hospital, Hirosaki, 6Breast Unit, Nagumo Clinic, Tokyo, JapanBackground: Brain metastases from breast cancer occur in 20%–40% of patients, and the frequency has increased over time. New radiosensitizers and cytotoxic or cytostatic agents, and innovative techniques of drug delivery are still under investigation.Methods: Five patients with brain metastases who did not respond to whole-brain radiotherapy and then received bevacizumab combined with paclitaxel were identified using our database of records between 2011 and 2012. The clinicopathological data and outcomes for these patients were then reviewed.Results: The median time to disease progression was 86 days. Of five patients, two (40% achieved a partial response, two had stable disease, and one had progressive disease. In addition, one patient with brain metastases had ptosis and diplopia due to metastases of the right extraocular muscles. However, not only the brain metastases, but also the ptosis and diplopia began to disappear after 1 month of treatment. The most common treatment-related adverse events (all grades were hypertension (60%, neuropathy (40%, and proteinuria (20%. No grade 3 toxicity was seen. No intracranial hemorrhage was observed.Conclusion: We present five patients with breast cancer and brain metastases, with benefits from systemic chemotherapy when combined with bevacizumab.Keywords: brain, bevacizumab, metastatic breast cancer

The role of general nuclear medicine in breast cancer

International Nuclear Information System (INIS)

Greene, Lacey R; Wilkinson, Deborah

2015-01-01

The rising incidence of breast cancer worldwide has prompted many improvements to current care. Routine nuclear medicine is a major contributor to a full gamut of clinical studies such as early lesion detection and stratification; guiding, monitoring, and predicting response to therapy; and monitoring progression, recurrence or metastases. Developments in instrumentation such as the high-resolution dedicated breast device coupled with the diagnostic versatility of conventional cameras have reinserted nuclear medicine as a valuable tool in the broader clinical setting. This review outlines the role of general nuclear medicine, concluding that targeted radiopharmaceuticals and versatile instrumentation position nuclear medicine as a powerful modality for patients with breast cancer

Progress Report Oct to Dec 1975(2)

International Nuclear Information System (INIS)

1976-01-01

Progress report NO. 2 of Tehran Nuclear Research Centre outlines a brief description of the progress made in each section of the centre. A complete list of dissertations for Master's degrees studied at the Nuclear Research Centre and a list of new technical employee are given at the beginning of the report. Research activities in the third section include, isotope separation, laser research, radiation chemistry, reactor management, environmental research, neutron physics, reactor engineering, and nuclear medicine. The fourth section deals with education and training; technical support and health physics are discussed in sections five and six respectively

AZU-1: A Candidate Breast Tumor Suppressor and Biomarker for Tumor Progression

Energy Technology Data Exchange (ETDEWEB)

Chen, Huei-Mei; Schmeichel, Karen L; Mian, I. Saira; Lelie`vre, Sophie; Petersen, Ole W; Bissell, Mina J

2000-02-04

To identify genes misregulated in the final stages of breast carcinogenesis, we performed differential display to compare the gene expression patterns of the human tumorigenic mammary epithelial cells, HMT-3522-T4-2, with those of their immediate premalignant progenitors, HMT-3522-S2. We identified a novel gene, called anti-zuai-1 (AZU-1), that was abundantly expressed in non- and premalignant cells and tissues but was appreciably reduced in breast tumor cell types and in primary tumors. The AZU-1 gene encodes an acidic 571-amino-acid protein containing at least two structurally distinct domains with potential protein-binding functions: an N-terminal serine and proline-rich domain with a predicted immunoglobulin-like fold and a C-terminal coiled-coil domain. In HMT-3522 cells, the bulk of AZU-1 protein resided in a detergent-extractable cytoplasmic pool and was present at much lower levels in tumorigenic T4-2 cells than in their nonmalignant counterparts. Reversion of the tumorigenic phenotype of T4-2 cells, by means described previously, was accompanied by the up-regulation of AZU-1. In addition, reexpression of AZU-1 in T4-2 cells, using viral vectors, was sufficient to reduce their malignant phenotype substantially, both in culture and in vivo. These results indicate that AZU-1 is a candidate breast tumor suppressor that may exert its effects by promoting correct tissue morphogenesis.

Early breast cancer detection in the hospital setting

International Nuclear Information System (INIS)

Vega, A.; Ortega, E.; Garcia-Valtuille, R.; Erasun, F.; Millan, R.; Garijo, F.

1997-01-01

The purpose of this study is to evaluate the benefits of mammography in general and particularly as a screening method in the early detection of breast cancer in our hospital. All the cases of breast carcinoma registered in our section between 1989 and 1995 were reviewed retrospectively. The total number of carcinomas was 775, 168 (22%) of which were diagnosed solely on the basis of mammography. The percentage of carcinomas detected on the basis of mammography alone increased progressively (from 13% in 1989-1990 to 28% in 1994-1995), coinciding with a progressive rise in the volume of screening mammography. Early carcinomas, referring to those in stages O or I, represented 67% of those detected by mammography in general and 17% of those detected by palpation (p<0.001). The proportion was even greater among cases of carcinoma detected exclusively by screening mammography (78 versus 17%; p<0.001). Although mammography has been instrumental in increasing the rate of early detection of breast carcinoma in our center, a large number of patients still present with palpable lesions. Thus, a greater effort should be made to increase the practice of mammography in asymptomatic women. (Author) 13 refs

Progress report for '89

International Nuclear Information System (INIS)

Podest, M.

1990-08-01

The 1989 Progress Report presents the most important scientific and technical achievements of the Nuclear Research Institute's research work. Some specialized products prepared at or fabricated by the NRI are mentioned as well. (author). 24 figs., 8 tabs., 101 refs

C-Mod Collaboration Informal Technical Progress Report

International Nuclear Information System (INIS)

Kenneth W. Gentle

2007-01-01

The aims of the collaboration have not changed. A specific list of tasks was agreed upon during the Fall of 2006 in preparation for the 2007 C-Mod campaign by Earl Marmar, Head of the Alcator Project, Kenneth Gentle, Principal Investigator, and William Rowan, Collaboration Coordinator with the facilitation of Adam Rosenberg (DOE grant monitor for the collaboration). The activities follow the list of tasks and are discussed in this progress report

P38 delta MAPK promotes breast cancer progression and lung metastasis by enhancing cell proliferation and cell detachment.

Science.gov (United States)

Wada, M; Canals, D; Adada, M; Coant, N; Salama, M F; Helke, K L; Arthur, J S; Shroyer, K R; Kitatani, K; Obeid, L M; Hannun, Y A

2017-11-23

The protein p38 mitogen-activated protein kinase (MAPK) delta isoform (p38δ) is a poorly studied member of the MAPK family. Data analysis from The Cancer Genome Atlas database revealed that p38δ is highly expressed in all types of human breast cancers. Using a human breast cancer tissue array, we confirmed elevation in cancer tissue. The breast cancer mouse model, MMTV-PyMT (PyMT), developed breast tumors with lung metastasis; however, mice deleted in p38δ (PyMT/p38δ -/- ) exhibited delayed primary tumor formation and highly reduced lung metastatic burden. At the cellular level, we demonstrate that targeting of p38δ in breast cancer cells, MCF-7 and MDA-MB-231 resulted in a reduced rate of cell proliferation. In addition, cells lacking p38δ also displayed an increased cell-matrix adhesion and reduced cell detachment. This effect on cell adhesion was molecularly supported by the regulation of the focal adhesion kinase by p38δ in the human breast cell lines. These studies define a previously unappreciated role for p38δ in breast cancer development and evolution by regulating tumor growth and altering metastatic properties. This study proposes MAPK p38δ protein as a key factor in breast cancer. Lack of p38δ resulted in reduced primary tumor size and blocked the metastatic potential to the lungs.

WE-FG-207A-00: Advances in Dedicated Breast CT

International Nuclear Information System (INIS)

2016-01-01

investigating dedicated breast CT. The development of large-area flat-panel detectors with field-of-view sufficient to image the entire breast in each projection enabled development of flat-panel cone-beam breast CT. More recently, the availability of complimentary metal-oxide semiconductor (CMOS) detectors with lower system noise and finer pixel pitch, combined with the development of x-ray tubes with focal spot dimensions similar to mammography systems, has shown improved spatial resolution and could improve visualization of microcalcifications. These technological developments promise clinical translation of low-dose cone-beam breast CT. Dedicated photon-counting breast CT (pcBCT) systems represent a novel detector design, which provide high spatial resolution (∼ 100µm) and low mean glandular dose (MGD). The CdTe-based direct conversion detector technology was previously evaluated and confirmed by simulations and basic experiments on laboratory setups [Kalender et al., Eur Radiol 22: 1–8, 2012]. Measurements of dose, technical image quality parameters, and surgical specimens on a pcBCT scanner have been completed. Comparative evaluation of surgical specimens showed that pcBCT outperformed mammography and digital breast tomosynthesis with respect to 3D spatial resolution, detectability of calcifications, and soft tissue delineation. Major barriers to widespread clinical use of BCT relate to radiation dose, imaging of microcalcifications, and adequate coverage of breast tissue near the chest wall. Adequate chest wall coverage is also technically challenging but recent progress in x-ray tube, detector and table design now enables full breast coverage in the majority of patients. At this time, BCT has been deemed to be suitable for diagnostic imaging but not yet for screening. The mean glandular dose (MGD) from BCT has been reported to be between 5.7 to 27.8 mGy, and this range is comparable to, and within the range of, the MGD of 2.6 to 31.6 mGy in diagnostic mammography

WE-FG-207A-00: Advances in Dedicated Breast CT

Energy Technology Data Exchange (ETDEWEB)

NONE

2016-06-15

investigating dedicated breast CT. The development of large-area flat-panel detectors with field-of-view sufficient to image the entire breast in each projection enabled development of flat-panel cone-beam breast CT. More recently, the availability of complimentary metal-oxide semiconductor (CMOS) detectors with lower system noise and finer pixel pitch, combined with the development of x-ray tubes with focal spot dimensions similar to mammography systems, has shown improved spatial resolution and could improve visualization of microcalcifications. These technological developments promise clinical translation of low-dose cone-beam breast CT. Dedicated photon-counting breast CT (pcBCT) systems represent a novel detector design, which provide high spatial resolution (∼ 100µm) and low mean glandular dose (MGD). The CdTe-based direct conversion detector technology was previously evaluated and confirmed by simulations and basic experiments on laboratory setups [Kalender et al., Eur Radiol 22: 1–8, 2012]. Measurements of dose, technical image quality parameters, and surgical specimens on a pcBCT scanner have been completed. Comparative evaluation of surgical specimens showed that pcBCT outperformed mammography and digital breast tomosynthesis with respect to 3D spatial resolution, detectability of calcifications, and soft tissue delineation. Major barriers to widespread clinical use of BCT relate to radiation dose, imaging of microcalcifications, and adequate coverage of breast tissue near the chest wall. Adequate chest wall coverage is also technically challenging but recent progress in x-ray tube, detector and table design now enables full breast coverage in the majority of patients. At this time, BCT has been deemed to be suitable for diagnostic imaging but not yet for screening. The mean glandular dose (MGD) from BCT has been reported to be between 5.7 to 27.8 mGy, and this range is comparable to, and within the range of, the MGD of 2.6 to 31.6 mGy in diagnostic mammography

Progress report 1979

International Nuclear Information System (INIS)

1980-12-01

This progress report deals with technical and research work done at the AAEC Research Establishment in the twelve month period ending September 30, 1979. Work done in the following research divisions is reported: Applied Maths and Computing, Chemical Technology, Engineering Research, Environmental Science, Instrumentation and Control, Isotope, Materials and Physics

Technical Note: Validation of two methods to determine contact area between breast and compression paddle in mammography.

Science.gov (United States)

Branderhorst, Woutjan; de Groot, Jerry E; van Lier, Monique G J T B; Highnam, Ralph P; den Heeten, Gerard J; Grimbergen, Cornelis A

2017-08-01

To assess the accuracy of two methods of determining the contact area between the compression paddle and the breast in mammography. An accurate method to determine the contact area is essential to accurately calculate the average compression pressure applied by the paddle. For a set of 300 breast compressions, we measured the contact areas between breast and paddle, both capacitively using a transparent foil with indium-tin-oxide (ITO) coating attached to the paddle, and retrospectively from the obtained mammograms using image processing software (Volpara Enterprise, algorithm version 1.5.2). A gold standard was obtained from video images of the compressed breast. During each compression, the breast was illuminated from the sides in order to create a dark shadow on the video image where the breast was in contact with the compression paddle. We manually segmented the shadows captured at the time of x-ray exposure and measured their areas. We found a strong correlation between the manual segmentations and the capacitive measurements [r = 0.989, 95% CI (0.987, 0.992)] and between the manual segmentations and the image processing software [r = 0.978, 95% CI (0.972, 0.982)]. Bland-Altman analysis showed a bias of -0.0038 dm 2 for the capacitive measurement (SD 0.0658, 95% limits of agreement [-0.1329, 0.1252]) and -0.0035 dm 2 for the image processing software [SD 0.0962, 95% limits of agreement (-0.1921, 0.1850)]. The size of the contact area between the paddle and the breast can be determined accurately and precisely, both in real-time using the capacitive method, and retrospectively using image processing software. This result is beneficial for scientific research, data analysis and quality control systems that depend on one of these two methods for determining the average pressure on the breast during mammographic compression. © 2017 Sigmascreening B.V. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.