bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nanoporous silicon delivery vectors for breast cancer imaging.
Authors: Serda RE , Godin B , Bankson J , Decuzzi P , Ferrari M 
Published: December 2010

Abstract
Abstract #4003
Nano- and micro-sized delivery systems are emerging as powerful tools for the systemic delivery of therapeutic and imaging agents in different biomedical applications, from cancer to cardiovascular diseases. These delivery systems can be loaded with a multitude of drug molecules and contrast agents to simultaneously provide therapeutic and imaging capabilities. Following intravenous injection, these particles are transported by the blood stream into different vascular districts. We have recently introduced a multi-stage delivery system designed to overcome sequential biological barriers. The first stage, comprised of porous silicon microparticles, targets tumor-associated endothelium. Once arrested at the tumor site, second stage nanoparticles, carrying therapeutic and imaging agents are released into the tumor microenvironment by time-dependent degradation of the silicon vehicle. Free nanoparticles cross the endothelial barrier by the inherent leaky nature of the tumor vessel, a phenomenon known as enhanced permeation and retention. In this study, iron oxide nanoparticles serve as contrast agents for visualizing distribution in murine mammary tumors using magnetic resonance imaging.&#x2028; The silicon microparticles are hemispherical in shape, a design that facilitates margination and interaction of particles with the endothelium. Loading of iron oxide nanoparticles into the silicon microparticles was accomplished by covalent attachment. The loaded particles were characterized by Prussian Blue quantitation of iron, as well as SEM and TEM analysis. Human breast cancer xenografts were established in nude mice by injection of 4T1 mouse mammary carcinoma cells into fatpads of Crl Foxnu nude mice. At day 15, mice were intraveneously administered either free iron oxide nanoparticles, or 1 x 108 silicon microparticles, non-loaded or loaded with iron oxide nanoparticles. Magnetic resonance imaging was carried out using a 7 Telsa magnetic resonance imager. Serial sagittal T2-weighted images revealed tumors with hypointense contrast for animals injected with free and multi-stage encapsulated iron oxide nanoparticles at both 3 and 5 hr. A separate quantitative study compared iron and silicon content in lungs, liver, spleen, kidney, and tumor by inductive coupled plasma atomic emission spectroscopy analysis of organs from 25 mice 5 hrs following tail vein injections of the following systems: 1) saline control, 2) silicon microparticles (Si), 3) iron oxide nanoparticles, and 4) iron oxide loaded silicon particles.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4003.
Factors influencing false negative diagnosis of 3D-MRI in pre-operative breast cancer patients.
Authors: Hisamatsu K , Takiyama W , Hirabayashi N , Kaneko M , Ono T , Sakabe R , Stou Y , Saeki S , Mukaida H , Yamashita Y 
Published: December 2010

Abstract
Abstract #4005
Introduction: We presented 3D-MRI will be the useful breast imaging tool in diagnosing intraductal spread and tumor size in breast cancer patients (ASCO 2008). But, false negative cases were very important in breast conserving surgery and careful management was needed in 3D-MRI guided surgery. This study was to review imaging diagnosis using 3D-MRI and to evaluate factors influencing false negative diagnosis of 3D-MRI, retrospectively. Material and methods: From July 2000, pre-operative 3D-MRI was underwent 433 cases of breast cancer patients. Images were obtained 426 cases (98%). Tumor size between 3D-MRI and resected specimens were evaluated retrospectively. Cases with tumor size difference between 3D-MRI and resected specimens less than 1cm were defined related cases and cases with tumor size in 3D-MRI was 1cm more smaller than resected specimens were defined false negative cases. Investigated factors influencing false negative diagnosis of 3D-MRI were age, patterns of 3D-MRI images, presence of pre-operative chemotherapy, histological type, histological grade, microscopical invasive tumor size (mm) and presence of ductal spreading. From April 2005, the entire specimen was serially step cut and evaluated. Results: Tumor diameter from nipple side to lateral margin were measured by MRI and specimens, tumor size was correlated between MRI and specimens, significantly (n=118, r=07186, P &lt; 0.001). On Multivariate analysis revealed that factors influencing 3D-MRI diagnosis were presence of ductal spreading (p=0.0002), patterns of 3D-MRI images (p=0.06) and presence of pre-operative chemotherapy (P=0.04). Factors influencing false negative diagnosis of 3D-MRI were presence of pre-operative chemotherapy (P&lt;0.05), presence of ductal spreading (P&lt;0.01) and infiltration of lymphocyte in the edge of ductal spreading (P&lt;0.05). Selection for breast conserving surgery and margin width were based by 3D-MRI images. The proportion of breast-conserved surgery were obtained 89% (380/426 cases) and local failure seen only 6 cases (local failure rate 1.4%) in 3D-MRI guided surgery. (6-94 months, median follow up 51 months).&#x2028; Conclusion: These results suggest that MRI will be the useful breast imaging tool in diagnosing intraductal spread and tumor size in breast cancer patients. But, caution will be needed in cases with pre-operative systemic therapy and cases expected ductal spreading by other imaging tools.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4005.
Inflammatory breast cancer: defining breast magnetic resonance imaging features.
Authors: Le-Petross HT , Cristofanilli M , Qing Y , Jackson EF , Gong Y , Reed B , Hortobagyi GN , Yang WT 
Published: December 2010

Abstract
Abstract #4008
PURPOSE: &#x2028; Inflammatory breast carcinoma (IBC) is an aggressive cancer with radiological and clinical features of a heterogeneous disease. The clinical presentation of IBC is characterized by the sudden onset of breast erythema and edema, often without an associated palpable breast mass. Mammography is associated with variable, not descriptive findings and it is often not diagnostic. We planned to address the role of Magnetic Resonance Imaging (MRI) of the breast in women with newly diagnosed IBC.&#x2028; MATERIALS AND METHODS:&#x2028; We performed a retrospective analysis of newly diagnosed IBC cases evaluated at the University of Texas. M D Anderson Cancer Center between December 2003 and February 2008. Baseline breast MRI exams were performed on 1.5-Tesla (T) or 3.0-T GE scanners and included dynamic three-dimensional T1-weighted fast spoiled gradient echo sequences with parallel imaging after a bolus injection of gadolinium based IV contrast. Exams were reviewed in batches and the findings rated in accordance with the ACR BI-RADS MRI Lexicon. The following parameters were evaluated; presence and characteristics of breast masses and skin description. All patients had concomitant mammograms and ultrasound exams.&#x2028; RESULTS: &#x2028; Eighty women with a clinical diagnosis of IBC were included in the study with a median age of 52 years, (range, 25 to 78). MRI detected a primary breast lesion in 80 of 82 symptomatic breasts (98%), compared to only 53 of 78 (68%) with mammogram (p &lt; 0.0001). The most common MRI morphologic characteristic of the lesions was irregular margins (72%) with heterogeneous internal enhancement (82%). Qualitative evaluation of the enhancement pattern demonstrated wash-out in 85% of the cases.&#x2028; MRI detected skin thickening in 90% of the patients (average skin thickness of 8 mm [range, 4-17 mm]), compared to 69% with mammogram. Heterogeneous skin enhancement (82%) and nodular or irregular skin lesions (43%) were identified only with MRI. These skin lesions demonstrated a progressive enhancing pattern, in contrast to the rapid wash-out pattern expected for malignant breast lesion.&#x2028; CONCLUSIONS: &#x2028; This study establishes breast MRI as the most sensitive and accurate imaging modality in assessing the breast of IBC patients. The most common radiological features are represented by the presence of a primary breast lesion and global skin thickening with heterogeneous skin enhancement. The combination of morphology and enhancing pattern may provide information to understand the biology of this disease and accurately monitor residual disease during neoadjuvant therapies.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4008.
A novel combination therapy with histone deacetylase inhibitor and Aurora kinase inhibitor for “triple negative” breast cancers.
Authors: Samuel T , Fiskus W , Buser C , Bhalla K 
Published: December 2010

Abstract
Abstract #401
Background: Aurora A and B are essential for normal mitosis. Aurora A (AA) is amplified and/or co-overexpressed with Aurora B (AB) in over 50% of breast cancers, including the basaloid variety, “Triple Negative” breast cancers. MK-0457 (M) is a pan-Aurora kinase inhibitor that inhibits in vitro and in vivo tumor growth, as well as induces apoptosis of cancer cells. Aurora kinases are chaperoned by hsp90, and their down regulation is known to sensitize transformed cells to paclitaxel. Vorinostat (V) is a pan-histone deacetylase inhibitor (HA-HDI) that induces in vitro growth arrest, differentiation and apoptosis of human breast cancer cells. By inhibiting HDAC6 and inducing hyper-acetylation and inhibition of hsp90, V depletes the levels of hsp90 chaperoned proteins, including AA and AB kinase. Methods: AA amplification in MB-231 (“Triple Negative”) and BT-474 (HER-2 amplified) cells were determined by FISH and array-CGH. The cells were treated with M (50 to 250 nM) and/or V (0.5 to 2.0 μM) for 24 to 48 hours. Cell cycle status, DNA endoreduplication (PI staining) and apoptosis (Annexin V/PI staining) were determined by flow cytometry. Intracellular protein levels of p-AA or p-AB, AA and AB, p-survivin, survivin, were determined by immunoblot analyses. Results: Treatment with M or V induces cell cycle G2/M phase accumulation and apoptosis of the breast cancer cells. Dose-dependently, treatment with M depleted phosphorylated (p)-AA, -survivin, and -Ser10 H3 levels. V induced hsp90 acetylation and depleted the levels of AA, AB and survivin. Both M and V induced formation of multi-polar aberrant mitotic spindles. Co-treatment with M and V mediated more depletion of p-survivin, AA and AB levels, as well as synergistically induced apoptosis of MB-231 and BT-474 cells. In the orthotopic MB-231 xenograft breast cancer model, co-treatment with M and V caused significantly more tumor growth delay, lung metastases and survival than treatment with either agent alone. Treatment with V induced in vivo hsp90 hyper-acetylation in the mouse xenografts, as well as in the accessible tumors from patients with breast cancer. This was determined by immunoblot analysis of post-treatment versus pre-treatment tumors with the anti-acetylated-K69-hsp90 antibody, which was developed for these studies. Hsp90 hyper-acetylation was associated with in vivo depletion of AA and AB levels in the mouse xenografts. Co-treatment with M and V, versus treatment with either M or V, also led to greater in vivo attenuation of AA, AB and p-survivin. Conclusion: These studies support the rationale to evaluate the safety and efficacy of the combination of M and V, without or with paclitaxel, against breast cancers with AA amplification and/or overexpression.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 401.
MRI findings in women with triple negative breast cancer.
Authors: Hines SL , McLaughlin SA , Vallow LA 
Published: December 2010

Abstract
Abstract #4014
Background&#x2028; Preoperative magnetic resonance imaging (MRI) of the breasts in women with breast cancer (BC) has improved the detection of occult ipsilateral (I/L) and contralateral (C/L) malignancies. Breast MRI findings in patients with estrogen receptor (ER), progesterone receptor (PR), and HER2 negative (triple negative (TN)) disease have not been previously reported. Women with TN BC are at increased risk of distant metastases and a reduced survival vs. BC patients as a whole. One potential explanation may be the presence of occult disease. The role of bilateral breast MRI in these patients remains to be determined.&#x2028; Hypothesis&#x2028; Patients with TN BC are more likely to have occult malignancy identified by preoperative MRI vs. those with non-TN BC.&#x2028; Methods&#x2028; All newly diagnosed BC patients from 2003-2007 were reviewed. Information on age, race, histology, ER, PR, HER2, staging, treatment, MRI findings, subsequent investigations, and additional cancer diagnoses was recorded. The incidence of additional I/L or C/L malignany was calculated. The percentage of total patients initially felt to be candidates for partial breast irradiation who required a change in their cancer management was calculated.&#x2028; Results&#x2028; 55 (11%) were diagnosed with TN BC, of whom 52 women completed preoperative MRI. 456 (89%) had non-TN BC; 421 completed preoperative MRI. The median age among TN and non-TN patients was 62 years (Table 1). A majority of women in both groups were Caucasian. African-American women were more likely to be diagnosed with TN vs. non-TN disease (11% vs. 6%).&#x2028; &#x2028; I/L BC was documented in 13/52 (25%) of TN patients vs. 25% of non-TN patients. No C/L cancers were detected in the TN group (6% in the non-TN group). Of the TN group, 15 patients required a change in their treatment (29%) based on findings from MRI vs. 32% of non-TN patients.&#x2028; Conclusions&#x2028; Patients with a new diagnosis of TN BC are not at increased risk of occult malignancy than those with non-TN BC. 25% of patients with TN BC had additional I/L disease not previously detected on clinical examination, mammogram, or ultrasound. Of those with non-TN BC, 25% were diagnosed with an additional I/L and 6% with C/L malignancy. The benefit of MRI was limited by false positives, with a number of patients in both groups undergoing a benign biopsy.&#x2028; These results suggest that patients with TN BC are not more likely than those with non-TN disease to have additional occult I/L or C/L cancer. The incidence of additional disease remains high and preoperative MRI may be beneficial.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4014.
Proximity-based assays for the detection of activated HER3, HER2/HER3 heterodimers and HER3/PI3K complexes in formalin-fixed, paraffin-embedded cell line controls and tumors.
Authors: Mukherjee A , Badal Y , Nguyen X , Miller J , Pidaparthi S , Chen L , Newton A , Cheung J , Parry G , Williams S 
Published: December 2010

Abstract
Abstract #4040
Although kinase-defective, the role of the HER3 receptor in driving tumor growth through dimerization with other HER family members is well recognized. There is increasing interest in developing therapeutic strategies to interfere with signaling through this receptor, either directly or indirectly. At the same time, there is recognition that the activation of HER3 could be an important biomarker of drug response and resistance. In particular the HER2/HER3 heterodimer has been extensively studied and, among all the possible homo and heterodimers formed by HER receptors, is considered the most mitogenic because of the ability of HER3 to effectively couple to the pro-survival PI3K/Akt pathway.&#x2028; Using the VeraTag™ technology, we have developed a suite of assays designed to detect quantitatively the activation status of the HER3 receptor by measuring HER3-specific phosphorylation and formation of HER3 signaling complexes in formalin-fixed, paraffin-embedded (FFPE) cell line controls and tissue samples.These assays are dual antibody-based and measure complexes of proteins in close association since signal is generated only when the antibodies are bound to target-specific epitope sites proximal to one another. A capillary electrophoresis instrument equipped with laser-induced fluorescence provides a highly sensitive and quantitative read-out of the assay. We report data on assays which detect a ligand-induced, 2-5-fold change in HER2/HER3 heterodimer formation, a 10-20 fold change in phosphorylated HER3 signal and as high as a 10 fold change in HER3/PI3K complex formation in a series of cell line controls, spanning a wide range of HER2 and HER3 receptor levels. FFPE data were verified with results from co-immunoprecipitation using antibodies identical to those used in the VeraTag assay. The influence of the HER2 and HER3 levels on the formation of HER2/HER3 heterodimers and correlation with HER3 phosphorylation and formation of the PI3K adaptor complex will be discussed.&#x2028; In addition, we have used these assays to landscape HER3 activation in a number of tissues, including breast and ovarian tumors, focusing particularly on HER2 positive breast cancer, where the HER2/HER3 heterodimer is thought to play a particularly significant role.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4040.
The relationship between tumour NF-kB expression, hormone status and survival in primary invasive breast cancer.
Authors: Tannahill CT , Obondo C , Tovey S , Orange C , Doughty JD , Wilson CR , Cooke TG , McMillan DC , Edwards J 
Published: December 2010

Abstract
Abstract #4041
Breast cancer is one of the most common and lethal malignancies in the UK. Conventionally, prognosis is based on hormone status, tumours size, grade and lymph node involvement. We have recently observed that NF-kB expression and activation was associated with progesterone receptor (PR) expression irrespective of oestrogen receptor (ER) status in primary invasive breast cancer (Tannahill et al., unpublished observations). The aim of the present study was to examine the relationship between NF-kB, PR and survival in a selected cohort of ER positive tamoxifen treated primary invasive breast cancer.&#x2028; Immunohistochemistry was performed on 372 breast tumours, with full clinicopathological characteristics. Antibodies were directed total NF-kB and NF-kB phosphorylated at serine 536 (phospho NF-kB). Two observers independently scored expression using the weighted histoscore technique, and grouped expression as tertiles. There was a minimum follow-up period of 4.9 years and a median follow-up of 6.8 years. During follow-up 104 patients died, 65 of which died of their disease, 96 patients recurred, 70 of which was while on tamoxifen.&#x2028; Nuclear NF-kB, either total or phosphorylated, expression was not associated with recurrence or survival. However, when the cohort was subdivided into PR positive (n=220) and PR negative tumours (n=140), increased nuclear phospho NF-kB expression was associated with increased recurrence (p&lt;0.05) and increased recurrence on tamoxifen therapy (p&lt;0.05) in PR positive tumours. In contrast, increased nuclear phospho NF-kB expression was associated with decreased recurrence (p&lt;0.05) and decreased recurrence on tamoxifen therapy (p&lt;0.05) in PR negative tumours.&#x2028; The results of the present study suggest that the effect of nuclear expression of phospho NF-kb on outcome in ER positive primary invasive breast cancer is dependent on PR status. The study highlights the importance of patient selection for the evaluation of the use of NF-kb inhibitors in patients with breast cancer.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4041.
CAPC expression correlates with breast tumor progression and invasion.
Authors: Man Y , Zhang Z , Wang C , Gao L , Zhang X 
Published: December 2010

Abstract
Abstract #4044
Background: Recent studies identified a uncharacterized gene that encodes a molecule named as cytokeratin-associated protein in cancer (CAPC). RT-PCR analysis detected significant elevation of CAPC mRNA in 26 of 33 human breast cancers. Our current study attempted to elucidate CAPC protein expression profile in human breast tissues, to assess: [1] if CAPC expression is associated with tumor progression and invasion, and [2] if CAPC is co-expressed with BP1 and c-erbB2, two known invasiveness and aggressiveness-related proteins.&#x2028; Materials and Methods: Consecutive sections were prepared from paraffin-embedded breast tissues from 100 female patients with breast tumors that harbored co-existing normal, hyperplastic, in situ, and invasive components. Sets of four adjacent sections from each case were subjected to immunohistochemistry for CAPC, BP1, c-erbB2, and Ki-67. The expression status of these molecules in different tissue components were statistically compared.&#x2028; Results: In normal breasts and hyperplastic or in situ breast lesions, CAPC positive cells were generally distributed as duct or acinar clusters with a distinct boundary with their CAPC negative counterparts. Under low magnification of H&E stained sections, these CAPC positive duct or acinar clusters were morphologically indistinguishable from their CAPC negative counterparts. Under high magnification, however, the myoepithelial cell layers of these CAPC positive clusters were focally disrupted, and the associated epithelial cells often showed malignancy-associated nuclear alterations. Both the number of CAPC positive cells and the intensity of CAPC immunostaining linearly increased with tumor progression and invasion. In invasive lesions, a vast majority of cancer cells in over 80% of the cases expressed high levels of CAPC. A majority of the normal, benign, and malignant tumors with high levels of CAPC showed substantially higher expression of BP1 and c-erbB2, along with a higher proliferation index, compared to their morphologically similar CAPC negative counterparts . In non-mitotic cells, CAPC was localized mainly in the cytoplasm. In malignant mitotic cells, high levels of CAPC expression were localized close to the cell membrane, forming a ring-like structure surrounding condensed chromosomes. In contrast, no distinct CAPC was detected in normal or hyperplastic mitotic cells.&#x2028; Discussion: These findings suggest CAPC might be a tumor specific marker that could be used for the development of diagnostic and/or therapeutic agents.&#x2028; Acknowledgment: Supported in part by grant BCTR0706983 from The Susan G. Komen Breast Cancer Foundation and grant 2006CB910505 from the Ministry of Chinese Science and Technology Department.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4044.