bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3590: Use of four biomarkers to evaluate survival disparity between black women and white women 35 to 64 years of age at diagnosis with invasive breast cancer
Authors: Ma Huiyan , Lu Yani , Malone Kathleen E. , Strom Brian L. , Simon Michael S. , Deapen Dennis M. , Sullivan-Halley Jane , Press Michael F. , Bernstein Leslie 
Published: August 2012

Abstract
Purpose: To evaluate the extent to which the black-white disparity in mortality following breast cancer diagnosis is explained by the expression status of four biomarkers - estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and p53 protein. Methods: The four biomarkers were assessed in paraffin-embedded breast tumor tissue for 1204 (523 black, 681 white) women, ages 35-64 years at diagnosis, who participated in the Women's CARE Study, a population-based case-control study of newly incident breast cancer, and who accrued a median of 10 years follow-up. The impact of these biomarkers on black-white disparity in breast cancer-specific and all-cause mortality was determined by fitting multivariable Cox proportional hazards regression models. Results: The black-white disparity in breast cancer-specific mortality was 54% in an age- and study site-adjusted model (relative risk [RR], 1.54; 95% confidence interval [CI], 1.21 to 1.97); it declined to a 36% greater risk for black women than white women after additionally controlling the status of the four markers (RR, 1.36; 95% CI, 1.06 to 1.75). Similar results were observed for all cause-mortality. Separate analyses for triple negative (ER-/PR-/HER2-) and luminal A (ER+ and/or PR+ plus HER2-) tumors showed that the black-white differences in mortality were predominately observed for older (50-64 years) women with luminal A tumors (breast cancer-specific RR, 2.07; 95% CI, 1.16 to 3.70; all-cause RR, 2.21; 95% CI, 1.40 to 3.47). For luminal A tumors, the greater mortality risk for older black women was attenuated after adjustment for stage, comorbidities, and education, and was most evident for all-cause mortality. Conclusions: Black-white differences in mortality following breast cancer diagnosis vary by tumor biomarker subtypes.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3590. doi:1538-7445.AM2012-3590
Abstract 3600: Comparison of estrogen receptor expression in breast cancer cells by immunohistochemistry using the monoclonal antibodies SP1 and 1D5
Authors: Madeira Klesia P. , Daltoe Renata , Sirtoli Gabriela , Rezende Lucas , Silva Ian , Carvalho Alex , Rangel Leticia 
Published: August 2012

Abstract
Background: Accurate pathological analysis of biopsies is crucial for conclusive and precise disease diagnosis, prognosis and therapeutic guidelines. Evaluation of estrogen receptor (ER) expression in breast cancer (BC) is imperative in determining the disease prognosis, and patients' eligibility for hormonotherapy. Herein, ERα status was evaluated in 61 BC cases using two different anti-ERα monoclonal antibodies, Sp1 (rabbit) and 1D5 (mouse). Methods: Primary BC cases registered in two reference hospitals, with correspondent written informed consent, were used to generate in house tissue microarray platforms. ERα expression was accessed by immunohistochemistry using the monoclonal antibodies anti-ERα, SP1 and 1D5. Staining scoring followed the Allred method (PS, proportion score or percentage of stained cells; IS, intensity score). Concordance and correlation parameters were calculated using Kappa factor; Pearson, Spearman's, or intraclass correlation coefficient (CF). Staining patterns were compared by paired T-Test and Wilcoxon test. Findings: SP1 and 1D5 provided equivalent results (Concordance rate, 96.7%; Kappa factor, 0.921), whereas SP1 was more prone for positive results than 1D5 (2 samples diverged). Total concordance of PS was obtained (Pearson and intraclass CF, 0.7351 and 0.6193, respectively); however, concordance between the antibodies seems more accurate in higher PS values. Excellent SI correlation between antibodies was observed throughout the population (Spearman's CF, α=0.9150). Following the Allred score, 17 out of 42 positive BC samples diverged; always pointing 1D5 to weaker staining than SP1. When calculating Spearman's CF of Total Score (TS) within the population, excellent correlation between both the antibodies (α=0.9238) was noted; nonetheless, results were less concordant result among the BC positive cases (α=0.7743). Indeed, 20 samples were differentially classified using the antibodies (only 3 had higher TS with 1D5). Considering the mean TS of all samples, or of invasive ductal carcinoma, SP1 provided higher scores than 1D5 (p&lt;0.05). Interpretation: Despite the equivalence between the anti-ERα monoclonal antibodies, SP1 and 1D5, the former has proven superior to the latter with respect to the IS and TS. Therefore, we suggest the clinical use of SP1 while diagnosing BC, due to its higher accuracy in examining ER status; thus, enabling more accurate therapeutic decisions to treat the disease.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3600. doi:1538-7445.AM2012-3600
Abstract 361: PET imaging of antitumor responses with anti-4-1BB (anti-CD137)
Authors: Escuin-Ordinas Helena , Atefi Mohammad , Ng Charles , Sharp Leslie , Ribas Antoni 
Published: August 2012

Abstract
Agonistic antibodies to 4-1BB (CD137), a member of the tumor necrosis factor family expressed on activated T cells, are being tested for immunotherapy in patients with advanced cancers. Being able to study the mechanism of 4-1BB action in vivo using non-invasive approaches would help guiding its clinical development. We used positron emitting tomography (PET) with [18F]FDG to study how 4-1BB mAb modulates the immune system in a mouse model for cancer treatment. The administration of 1mg/kg of the 4-1BB mAb to Balb/c mice induced reproducible CT26 tumor regressions and improved survival (n=8 mice per group, p = 0.006 for survival by log rank test). The mean tumor size (mm) was also strikingly different (5.8 ± 0.20 4-1BB mAb group vs 8.3 ± 0.19 control, on day 7 after 4-1BB mAb; p &lt; 0.0009). All mice responded to the treatment and complete tumor shrinkage was achieved in 75% of cases, 14 days after 4-1BB mAb administration. Using microPET imaging there was markedly increased mean signal (% ID/g) of [18F]FDG at the tumor site and draining lymph nodes (18.4 ± 1.6 4-1BB mAb group vs. 10.3 ± 0.418 control group). Due to the shrinkage of the tumor in the treated group, we hypothesized this higher PET signal is the result of higher activity of immune cells in the site. In a metabolic probe in vitro uptake assay, there was a 7-fold increase in uptake of [3H]DDG in lymphocytes extracted from tumor-draining lymph nodes and a 2-fold increase in tumor infiltrating lymphocytes (TILS) of mice treated with 4-1BB mAb compared to untreated mice, supporting the in vivo PET data. In conclusion, increased uptake of [18F]FDG by PET scans visualizes 4-1BB mAB-induced anti-tumor immune responses and can be used as a pharmacodynamic readout to guide the development of this class of antibodies in the clinic.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 361. doi:1538-7445.AM2012-361
Abstract 3610: GW182 associates with circulating microvesicles and microRNA in human plasma
Authors: Brown Kirk , Millis Meredith , Smith Shannon E. , Yeatts Kim , Zhong Jason , Stark Adam , Kojima Yuka , Garcia Julie , Spetzler David B. 
Published: August 2012

Abstract
To date, microRNAs (miR) in human plasma have been discovered within circulating microvesicles (cMV), bound to Argonaute 2 and associated with HDL and LDL microvesicles. The protein GW182 shares an association with both multivesicular bodies and the Argonaute family of proteins. GW182 has the capacity to bind all human Argonaute proteins (1-4) and their associated miRs. In the cell, GW182 is associated with the membrane of multivesicular bodies and has the ability to congregate Argonaute-loaded RISC complexes. In addition, GW182 has been observed on the surface of purified exosomes. Here we investigated the relationship of GW182 with Argonaute and cMV in human plasma. A monoclonal antibody directed toward GW182 was used to capture the protein. This isolate also contained Argonaute proteins as determined by Western analysis. The co-precipitation of GW182 and Argonaute suggests that these two proteins retain their functional relationship in plasma. RNA was then isolated from precipitates for miR detection and analysis. The GW182-associated miR profile from human plasma contained individual miRs whose abundance either equaled or surpassed that of their matched Argonaute 2 immuno-precipitated miRs. This implies that GW182 maintains an association with the family of Argonaute proteins and a subset of cMV in human plasma. Phenotypic analysis of GW182-associated human plasma microparticles was performed using flow cytometry with a Beckman Coulter MoFlo XDP. A subpopulation of plasma-derived cMV was observed that co-expressed tetraspanins, GW182 and Argonaute 2. Since tetraspanins are transmembrane proteins highly associated with cMV, these results suggest that both GW182 and Argonaute can associate with cMV in human plasma. Thus, precipitation of GW182 enables the isolation and purification of miRs from human plasma including those bound to Argonaute 1-4 and a subset of cMV.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3610. doi:1538-7445.AM2012-3610
Abstract 3613: Methylated PLK2 predicts response to taxanes
Authors: Coley Helen M. , Chivers Pritlata , Syed Nelofer , Crook Tim 
Published: August 2012

Abstract
Polo-like-kinases (Plk) are a family of mitotic kinases with close structural similarity but showing functional diversity. Plk2 was originally described as an early response gene as is sometimes referred to as Snk. It has been shown to be a transcriptional target of p53 and activates a G2M checkpoint. Following a screening of a number of taxane resistant ovarian cancer cell lines we saw a close association with down-regulation of PLK2 and the extent of taxane resistance. Methylation analysis including methylation specific PCR (MSP) and pyrosequencing showed heavy methylation of CpG islands in the promoter region. We also saw that when sensitivity to paclitaxel is restored by a process of resistance reversal by growing cells in a drug free environment and this corresponded with upregulation of PLK2. We have also then gone on to look at a range of taxane-resistant breast cancer cell lines and have in many cases seen an association of PLK2 down-regulation with the acquisition of resistance. Translational studies using clinical biopsies and matched serum samples from a total of 43 ovarian cancer patients have indicated that the presence of methylated PLK2 in ovarian cancer tissue at first presentation may predict future relapse on platinum and taxane combination therapy. We also saw an association of presence of methylated PLK2 in either serum or tumour tissue with reduced survival. At present we are examining a series of samples from 40 breast cancer patients in the neo-adjuvant setting treated with taxane containing regimens to look for the association of PLK2 methylation with clinical outcome. We propose that methylated PLK2 is a useful marker of chemoresponse in ovarian and breast cancers.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3613. doi:1538-7445.AM2012-3613
Abstract 3619: The absence of cleaved caspase-3 in circulating tumor cells detected using a non-enrichment-based assay
Authors: Metzner Thomas J. , Bethel Kelly , Cho Edward H. , Luttgen Madelyn S. , Lazar Daniel C. , Uson Maria L. , Nieva Jorge J. , Bazhenova Lyudmila , Kolatkar Anand , Kuhn Peter 
Published: August 2012

Abstract
Background: The role of cleaved caspase-3 as an integral player in the apoptotic process of mammalian cells has prompted the investigation of an assay to detect cleaved caspase-3 in circulating tumor cells (CTCs) as one way to assess CTC viability. Methods: Using a previously developed non-enrichment based assay, nucleated blood cells and CTCs are adhered to a single slide. An antibody for cleaved caspase-3 was incorporated into the assay in addition to the existing antibodies for cytokeratin (to identify tumor cells) and CD45 (to identify white blood cells), as well as a nuclear stain (DAPI). The modified assay was initially tested on cultured MCF 10a cells spiked into normal donor blood. Before spiking, apoptosis was induced in these cells using staurosporine. Following validation of the assay in cell lines, the assay was performed using blood samples from 9 different breast cancer patients, as well as 3 different normal donor samples. Results: CTCs were detected in the patient samples as single cells, as well as clusters. The results of the assay showed that only 1 out of 896 detected CTCs was positive for cleaved caspase-3 (0.11%). Of these CTCs, 134 of them were found to be in clusters, and all 134 were negative for cleaved caspase-3, indicating that whether in clusters or as single cells, the vast majority of CTC's detected with this assay are not undergoing irreversible apoptotic processes via cleaved caspase-3. The results also showed that 0.40% of white blood cells in healthy donors expressed cleaved caspase-3, compared to 0.51% of the white cells in cancer patients, indicating that healthy donors and cancer patients express cleaved caspase-3 in their white blood cells at nearly the same rate. Conclusions: The morphologic characterization used in this platform to select healthy-appearing cells identifies a population of circulating tumor cells with virtually no evidence of caspase-related ongoing apoptosis, a finding that supports the morphologic impression of viability.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3619. doi:1538-7445.AM2012-3619
Abstract 362: [18F]-FLT Positron Emission Tomography can be used to image the response of sensitive tumours to PI3-Kinase inhibition with the novel agent GDC-0941.
Authors: Cawthorne Christopher , Wilson Ian A. , Danikas Antonios , Burrows Natalie , Radigois Mark , Gregory Jamil , Smigova Alison , Babar Muhammed , Williams Kaye J. 
Published: August 2012

Abstract
Emerging targeted therapeutics are characterised by high efficacy rates in selected patient sub-populations as well as potentially high running costs. This calls for companion diagnostic tools that contribute to the better management of such therapies, in terms of patient selection and monitoring therapeutic response. The Phosphatidylinositide 3-kinase pathway is deregulated in a range of cancers, and several targeted inhibitors are entering the clinic. This study aimed to investigate whether the PET tracer [18F]-FLT is suitable to mark the effect of the novel PI-3K inhibitor GDC-0941 which has entered Phase II clinical trial. Methods Nude mice bearing U87 and HCT116 xenografts were imaged at baseline with [18F]-FLT (10-15MBq per mouse produced using a GE Tracerlab). GDC-0941 or vehicle was then administered at a concentration of 50mg/kg twice daily by gavage and animals were rescanned at acute (∼18h) and chronic (∼186h) timepoints post-therapy. Standard uptake value (SUV)s for tumour uptake were calculated, and tissue was analysed at sacrifice for phospho-AKT. To generate normalised uptake values (NUV)s the SUV [tumour] was divided by the SUV for heart. NUV figures are given for the 100-105min post-injection time interval. Results Growth of U87 xenografts was significantly inhibited by GDC-0941 treatment throughout the course of the study (average growth rate of treated = –1.0±9.3 mm3, control = 69.2±22.1mm3 per day). Growth of HCT116 xenografts was not significantly different between groups (average growth rate of treated = 34.6±15.9 mm3, control =54.8±11.1 mm3 per day). Tumour uptake of [18F]-FLT was significantly reduced in treated animals bearing U87 xenografts at the acute timepoint compared to baseline (NUVmax 2.17 ± 0.38 vs 1.59 ± 0.29, p&lt;0.01), whereas uptake in HCT116 tumours was unchanged. Analysis of the downstream marker phospho-AKT showed that this was decreased in U87, but not HCT116, tumours. Conclusion [18F]-FLT is a strong candidate for the non-invasive measurement of GDC-0941 action. In addition to FLT, we are assessing the performance of a range of other imaging agents, including proprietary tracers, that can potentially bring value in monitoring of PI3-kinase targeting therapies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 362. doi:1538-7445.AM2012-362
Abstract 3624: Circulating sEGFR arises through a fibronectin/integrin-regulated proteolytic cleavage event: Analogy to HER2 shedding
Authors: Wilken Jason A. , Perez-Torres Marianela , Nieves-Alicea Rene , Cora Elsa M. , Christensen Trace A. , Baron Andre T. , Maihle Nita J. 
Published: August 2012

Abstract
A circulating isoform of EGFR has been identified as an emerging serum biomarker in cancer patients. Serum concentrations of EGFR have been evaluated as screening, diagnostic, prognostic, and theragnostic markers for diverse human malignancies, including breast, ovarian, endometrial, colorectal, and lung cancer. Yet full-length EGFR is rarely shed from normal or malignant cells. Here we demonstrate that an alternately spliced EGFR isoform, termed ‘sEGFR,’ gives rise to the circulating sEGFR protein through proteolytic cleavage of a cell surface precursor. This cleavage event is inhibited by fibronectin and stimulated by both an anti-Δ5/α1 integrin antibody and the metalloprotease activator 4-aminophenylmercuric acetate. Preliminary results identify ADAM17/TACE as at least one mediator of sEGFR shedding. Shed sEGFR binds to EGF with high affinity. Two FDA-approved therapeutic anti-EGFR antibodies, cetuximab (Erbitux) and panitumumab (Vectibix), inhibit shedding of sEGFR, implicating sEGFR as a potential alternative target for these antibodies, consistent with previous studies indicating that baseline serum sEGFR concentrations may predict responsiveness to anti-EGFR-targeted therapy. These observations bear striking similarity to aspects of trastuzumab regulation of HER2, shedding, and, by analogy, may have implications for the design of future clinical trials using EGFR-directed therapeutics, including cetuximab and panitumimab.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3624. doi:1538-7445.AM2012-3624
Abstract 3643: Early detection of cancer in the general population - a blinded case control study of p53 auto-antibodies in colorectal cancer in UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)
Authors: Pedersen Johannnes W. , Gentry-Maharaj Aleksandra , Fourkala Rania , Dawnay Anne , Burnell Matthew , Zaikin Alexey , Pedersen Anders , Jacobs Ian , Menon Usha , Wandall Hans H. 
Published: August 2012

Abstract
Purpose: Recent reports from cancer screening trials in high-risk populations suggest that autoantibodies are present prior to clinical diagnosis. However there are few data on the role of autoantibody signatures in cancer screening in the general population. Methods: Informative p53 peptides were identified on an autoantibody microarray with 15-mer overlapping peptides covering the complete p53 sequence using sera from patients with colorectal cancer. The selected peptides were evaluated in a blinded case control study using stored serum from the multimodal arm of UKCTOCS where women gave annual blood samples. Cases were postmenopausal women who developed colorectal cancer following recruitment, with 2 or more serum samples preceding diagnosis. Controls were age-matched women with no history of cancer. Results: The 50,640 women randomised to the multimodal group were followed up for a median of 6.8 (inter-quartile range 5.9-8.4) years. Colorectal cancer notification was received in 101 women with serial samples of whom 97 (277 samples) had given consent for secondary studies. They were matched 1:1 with 97 controls (276 serial samples). The four most informative peptides identified 25.8% of colorectal cancer patients with a specificity of 95%. The median lead time was 1.4 (range 0.12-3.8) years prior to clinical diagnosis. Conclusion: Our findings suggest that in the general population, autoantibody signatures are present during preclinical disease and may be of value in cancer screening. In colorectal cancer screening in particular, where the current need is to improve compliance, it suggests that p53 autoantibodies may contribute towards risk stratification.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3643. doi:1538-7445.AM2012-3643
Abstract 3650: Serous ovarian carcinoma patients with high alpha-folate receptor had poorer outcome by reducing cytotoxic chemo-response through anti-apoptotic pathway
Authors: Huang Ching-Ting , Chen Yu-Li , Chang Ming-Cheng , Huang Chia-Yen , Chiang Ying-Cheng , Cheng Wen-Fang 
Published: August 2012

Abstract
The alpha-folate receptor (α-FR) is highly expressed in various non-mucinous tumors of epithelial origin, including ovarian carcinoma. Semi-quantitative reverse-transcription polymerase chain reactions for α-FR expression were performed in 91 specimens of serous ovarian carcinomas. Furthermore, in vitro apoptotic experiments were tested in the original OVCAR-3 tumor cells and various OVCAR-3 α-FR-transfectants. In our study, the serous ovarian cancer patients with advanced stages (stage I: 0.451, stage II: 0.415, stage III: 0.652, stage IV: 0.768, p=0.004) had a significantly higher α-FR expression compared to those with early stages. Patients with an increased α-FR expression level had poorer responses to chemotherapy (odds ratio (OR): 8.97 (95% confidence interval (CI): 1.40-57.36), p=0.021). An increased α-FR expression level was an independently poor prognostic factor for DFI (Hazard ratio (HR): 2.45 (95% CI: 1.16-5.18), p=0.02) and had a negative impact on OS of these serous ovarian cancer patients (HR: 3.6 (95% CI: 0.93-13.29), p =0.03) by multivariate analyses. α-FR inhibited cytotoxic drug-induced apoptosis in our in vitro apoptotic assays. α-FR could induce chemo-resistance via regulating the expression of apoptosis-related molecules, Bcl-2 and Bax. Therefore, α-FR can be a potential biomarker for the prediction of chemotherapeutic responses and clinical prognosis. It also could be the target of treating ovarian cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3650. doi:1538-7445.AM2012-3650