bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 454: Glucocorticoids enhance metastatsis and tumorigenicity in a triple negative breast cancer cell line
Authors: Lu Yen-Shen , Gao Ming , Wu Pei-Fang , Lin Ching-Hung , Yeh Ling-Chun , Chen Chun-Wei , Cheng Ann-Lii 
Published: August 2012

Abstract
Glucocorticoid (GC) is commonly co-administered with chemotherapy to prevent drug-induced allergic reaction, nausea, and vomiting. We have previously reported that GC may affect growth and chemosensitivity of carcinoma cells via diverse mechanisms (Lung Cancer 2006, 53:303-10; J Endocrinol 2006,188:311-9; World J Gastroenterol. 2005, 28:6373-80). Along this line, we further explored the effect of GC on breast cancer cells. Treatment of dexamethasone (DEX) resulted in early axillary lymph node metastases, and increased the number of lung and liver metastases in an orthotopic xenograft model of a triple negative breast cancer cell line (MDA-MB-231) in nude mice (BALB/cAnN.Cg-Foxn1nu/CrlNarl). In tail vein injection assay of cancer metastasis, treatment of DEX dramatically enhanced the lung metastatic potential of a lung-seeking sub-clone, MDA-MB-231-Lu2 (derived from lung metastasis of MDA-MB-231 cells after two in vivo passages in nude mice using intracardiac injection). To explore the mechanism of GC-induced metastasis of breast cancer cells, we performed several in vitro studies. While DEX does not affect the proliferation rate of MDA-MB-231 cells according to MTT assay, treatment of DEX enhanced the tumorigenicity of the cells according to soft agar tumor sphere formation assay. On the other hand, treatment of DEX decreased tumorigenicity in two non-TNBC cell lines, MCF7 and T47D cells. Using quantitative polymerase chain reaction and Western blots assay, we found that treatment of DEX increased the expression of Slug, an epithelial-to-mesenchymal transition (EMT) related gene, and angiopoietin-like 4 (ANGPTL4), an important lung metastasis related gene, in MDA-MB-231 cells, but not in MCF7 and T47D cells. Using transwell migration/invasion assay (with or without matrigel above the membrane), we found that the conditioned medium of DEX-treated lung and liver tissues of mice attracted the MDA-MB-231 cells and promote migration/invasion. In conclusion, GC enhances metastasis and tumorigenicity in MDA-MB-231 cells, a triple negative breast cancer cell line. Whether GC may have a detrimental clinical effect on this subtype of breast cancer patients need to be verified.
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 454. doi:1538-7445.AM2012-454
Abstract 4540: Pyruvate kinase M2 (PKM2) associated with poor prognosis in gastric signet ring cell carcinoma
Authors: Lim Jae Yun , Yoon Sun Och , Hong Soon Won , Kim Jong Won , Choi Seung Ho , Cho Jae Yong 
Published: August 2012

Abstract
Background: PKM2 (M2 isoform of pyruvate kinase) was identified as a driver of aerobic glycolysis, leading to cell growth and tumor development. PKM2 is usually known to overexpress in cancer, however, there are still remaining questions about the function and the potential as anti-cancer treatment target. We investigated the expression status of PKM2 in gastric cancer tissues and evaluated the possibility of biomarker and anticancer target. Methods: Paraffin-embedded tissue microarray blocks of gastric adenocarcinoma tissue specimens were obtained from 363 gastric cancer patients. All patients underwent curative gastric resection from 1999 to 2007 and distributed from stage I to IV and their clinical characteristics were collected. IHC (Immunohistochemical) assay was performed to evaluate PKM2 expression levels. The correlation of PKM2 expression level with gastric cancer prognosis / stage / histology was evaluated. Results: In our previous microarray study using 60 gastric cancer tissues, we identified PKM2 mRNA overexpressed in cancer tissue than non-cancer tissue (P&lt;0.01). In IHC assays, PKM2 expression level was classified to score 0 (negative, n=185), 1 (weak positive, n=136), and 2 (strong positive, n=42). 49% of gastric cancer tissues presented PKM2 expression (weak or strong positive). PKM2 expression had no relation with prognosis (p=0.913, recurrence free survival) and TNM stage (p=0.825). Intestinal and diffuse type cancer manifested different PKM2 expression pattern and signet ring cell carcinoma manifested 26.6% PKM2 expression. Within same Lauren classification, there was no significant difference of prognosis according to PKM2 expression except signet ring cell carcinoma. In signet ring cell cancer (n=78), PKM2 expression was related to poor overall survival (p=0.029) Conclusion: PKM2 protein expression was not correlated with gastric cancer prognosis. Only in signet ring cell gastric cancer, overexpressed PKM2 was associated with poor overall survival. The role of PKM2 should be further verified in signet ring cell gastric cancer model to find clinical significance in this subtype of gastric 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 4540. doi:1538-7445.AM2012-4540
Abstract 4541: Metabolomic diagnosis of prostate cancer from urine
Authors: McDunn Jonathan , Whitaker Hayley , Li Zhen , Adam Klaus-Peter , Milburn Michael , Neri Bruce , Neal David 
Published: August 2012

Abstract
There is a critical unmet need for new diagnostic tests to both determine if a patient has prostate cancer and whether that cancer is aggressive and therefore requires aggressive management. In this study we performed global metabolomic profiling on the post-DRE urine sediments of twenty-four men referred to the urologist with concern of prostate cancer. Eight of these men presented with benign prostatic conditions leading to a raised PSA while the remaining sixteen patients had clinical T3 prostate cancer. Global metabolomic profiling was carried out on methanolic extracts of these urine sediments. The resulting data sets were found to contain 256 metabolites based on spectral comparison against an in-house chemical reference library of over 2500 authentic standards. A subset of prostate cancer patients, but no patients with benign prostatic conditions, had elevated sarcosine abundance in their urine sediments. Patients with elevated sarcosine had a distinct metabolic signature that included sixty-five other differentially abundant metabolites, predominantly amino acids and their catabolites, differentiating these patients from the rest. The remaining prostate cancer patients could be differentiated from the patients with benign prostatic conditions based on their abundance profiles of acyl carnitines (increased) and uridine (reduced). Stable isotope dilution assays for select analytes confirmed these results, and several multianalyte algorithms were found to have good performance for the diagnosis of prostate cancer (AUROC &gt; 0.8). Both metabolic presentations of prostate cancer exhibited biochemical hallmarks of multiple acyl-coA dehydrogenase deficiency, an inborn error of metabolism that can be due to impaired activity of the mitochondrial electron transfer flavoprotein/quinone oxidase complex. These data indicate that post-DRE urine sediment profiling could provide valuable information regarding the need to refer the urologic patient for prostate biopsy and may hold additional insight into the molecular pathogenesis of prostate 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 4541. doi:1538-7445.AM2012-4541
Abstract 4545: Positron emission tomography (PET) of TSPO expression in preclinical models of human cancer
Authors: Tang Dewei , Hight Matthew R. , Mckinley Eliot T. , Fu Allie , Buck Jason R. , Smith Adam , Tantawy Mohammed Noor , Colvin Daniel , Ansari Mohammad S. , Nickels Mike , Manning Henry C. 
Published: August 2012

Abstract
There is a critical need to develop and rigorously validate molecular imaging biomarkers to aid diagnosis and characterization of human cancer. Elevated expression of translocator protein (TSPO) has been shown to predict disease progression and aggressive, invasive behavior in a variety of solid tumors. Thus, noninvasive molecular imaging of TSPO expression could form the basis of a novel, predictive cancer imaging biomarker. In quantitative preclinical PET studies, we have evaluated a high-affinity pyrazolopyrimidinyl TSPO imaging ligand ([18F]DPA-714) and an aryloxyanilide-based TSPO imaging ligand ([18F]PBR06), as translational probes for quantification of TSPO levels in glioma, breast cancer, and colorectal cancer. In these studies, glioma-bearing rats or genetically engineered mice bearing spontaneously arrising breast or colorectal cancers were imaged with TSPO PET ligands in a microPET system. Dynamic images were acquired simultaneously upon injection of radioactive TSPO PET ligands. Arterial blood was collected to derive the input function (AIF), with HPLC radiometabolite analysis performed upon select samples for AIF correction. Compartmental modeling was performed using the corrected AIF. Immediately following imaging, tumor and healthy surrounding tissues were harvested for validation by western blotting and immunohistochemistry. Our results illustrate the feasibility of using TSPO PET ligands for visualization of TSPO-expressing tumors of the brain, breast and colon. Importantly, both [18F]DPA-714 and [18F]PBR06 appear suitable for quantitative assay of tumor TSPO levels in vivo. Given the relationship between elevated TSPO levels and poor outcome in oncology, these studies suggest the potential of these imaging agents to serve as a novel predictive cancer imaging biomarkers.
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 4545. doi:1538-7445.AM2012-4545
Abstract 455: Phospho-ERK as a predictor for different ways of metastasis and / or survival in patients with metastasized colon cancer
Authors: Strohäker Jens , Falch Claudius , Weyhern Claus Hann von , Adam Patrick , Königsrainer Alfred , Fend Falko , Brücher Björn LDM 
Published: August 2012

Abstract
Background: Not much is known about different signalling pathways and its influence on metastasis in colon cancer. Phospho-ERK (pERK) is a downstream-target of K-Ras within the EGFR-Pathway. The goal of our investigations was the evaluation of the MAP-Kinase-cascade in regard to different ways of metastasis. Methods: 98 patients with adenocarcinom of the colon and a postoperative pT2/3-status, who underwent surgical resection between 2006 and 2008 at the University of Tübingen had been included within the study collective. 53 patients had no metastasis (control group), while 45 patients revealed primary metastasis: lymphogenetic metastasis (n=20), hepatic spread (n=20) and multiple metastasize (n=5). On a tissue-micro-Array pERK was stained by immunohistochemistry, the analysis was done semiquantitatively. Results: The graduation in immunohistochemistry was done as followed: negative staining (n=31), weak positive staining (n=36), moderate staining (n=20) and strong staining (n=11). 19 out of 31 negative patients (61%) revealed metastasis, while this had been 17 out of 36 weak positive (47%), 6 out of 20 (30%) moderate and 4 out of 11 (36%) strongly positive stained patients (p=0.229). No significant correlation was observed for lypmhogenetic (p=0.683) or multiple metastatic localization (p=0.666) and the pERK-expression. A significant correlation between the pERK-expression and the number of hepatic metastasis was observed (p=0.049). Additionally pERK-negative patients (31/98 = 32%) revealed a significant worse survival compared to those with positive pERK-staining (p=0.003). Conclusion: Our first results show, that a weak pERK-expression is correlated with a higher incidence in patients with liver metastasis. Patients without a pERK-expression revealed a worse survival compared to patients with pERK-expression.
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 455. doi:1538-7445.AM2012-455
Abstract 4553: Multiplexed, digital gene expression and fusion transcript analysis to screen for EML4-ALK positive lung cancer
Authors: Lira Maruja E. , Kim Tae-Min , Huang Donghui , Deng Shibing , Koh Youngil , Jang Bogun , Lee Se-Hoon , Chung Doo Hyun , Kim Woo Ho , Kim Dong-Wan , Mao Mao 
Published: August 2012

Abstract
Purpose: EML4-ALK fusions occur in approximately 5% of non-small cell lung carcinoma and define a subpopulation of lung cancer patients highly responsive to ALK kinase inhibitors. Current methodologies for detecting presence of ALK rearrangements are labor-intensive, costly, and not ideally suited for screening large number of patient samples. To allow for a sensitive, facile, and inexpensive methodology to detect EML4-ALK fusions, we developed a direct transcript profiling to detect common variants of EML4-ALK fusions. Experimental Design: Using a single multiplex assay, we simultaneously interrogated presence of EML4-ALK transcripts and ALK 3′ over-expression in 8 ALK-positive and 22 ALK-negative NSCLC samples previously tested by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). For controls, we also tested ALK-positive cancer cells lines NCI-H3122 and NCI-H2228, and an ALK-negative cell line A549. Purified RNA from formalin-fixed paraffin-embedded (FFPE) tissue sections was hybridized in duplicates to a biotinylated capture probe and a color-coded reporter probe designed to hybridize to sequences spanning EML4-ALK junction. In addition, multiple probes were created to hybridize within 5′ and 3′ regions of ALK transcript to detect discordant levels between the breakpoint, indicative of fusion event. Purified hybridization complexes are immobilized and aligned on a cartridge where a microscope CCD camera images and counts the molecular color-coded tags attached to reporter probes. The number of reporter counts corresponds to the number of transcripts being interrogated. Results: With this assay, we obtained 100% concordance in EML4-ALK fusion calls to results generated by FISH and IHC analyses. Similar findings were obtained for control cancer cell lines. The assay is highly reproducible and sensitive, detecting ALK-fusion transcripts even in samples with low tumor content. Using the combined strategy of fusion detection and ALK 5′ and 3′ transcript quantification, we were able to validate the status of one patient negative for ALK rearrangement by FISH but positive for ALK protein expression by IHC. Conclusions: We have developed a novel and sensitive methodology to screen for common EML4-ALK fusions in NSCLC. The assay is inexpensive, easy to perform, high-throughput and compatible with FFPE tissue samples. This is a promising technology highly suitable for screening large numbers of tumor samples without the need for cDNA synthesis and PCR amplification.
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 4553. doi:1538-7445.AM2012-4553
Abstract 4556: Epidermal growth factor signaling alterations in uterine papillary serous carcinoma (UPSC) associate with survival
Authors: Groeneweg Jolijn W. , Tambouret Rosemary H. , Borger Darrell R. , Foster Rosemary , Rueda Bo R. , Growdon Whitfield B. 
Published: August 2012

Abstract
Endometrial cancer is the most common gynecologic malignancy and the majority of patients are cured with surgery alone. A substantial subset of patients, however, present with high grade uterine papillary serous carcinoma (UPSC) and these patients account for a disproportionate degree of the recurrence, chemoresistance and death associated with endometrial cancer. Novel treatment strategies incorporating molecularly targeted therapies would be of great value in effective clinical management of these tumors. HER2 (ErbB2) hyperactivity has been associated with 10-20% of UPSC, though efforts to target this signature with trastuzumab have yielded no response in a recent prospective trial. In breast cancer, HER2/HER3 (ErbB2/ErbB3) dimerization has been associated with trastuzumab resistance. The expression profile of HER3 in UPSC is currently unknown. The objective of this investigation was to characterize HER2 and HER3 expression in a UPSC series and correlate these findings with clinical outcomes including survival. Under an IRB approved protocol, we identified 33 patients who underwent initial surgical staging at our institution between 2000 and 2009 with archival formalin fixed, paraffin embedded blocks and complete clinical follow up data. These tumor samples were subjected to immunohistochemistry (IHC) for HER2 and HER3 as well as fluorescent in situ hybridization (FISH) to assess the amplification status of the HER2 gene. Non-parametric tests were utilized to test correlation between detected levels of HER2 or HER3 protein expression and HER2 gene amplification and survival analysis was performed using the Kaplan-Meier method. HER2 gene amplification was observed in 34% of the cohort while HER2 protein over-expression, defined as 2+ or 3+ staining, was found in 59% of samples tested. HER2 gene amplification was associated with high HER2 protein expression (p &lt; 0.05). Moreover, HER2 gene amplification was significantly associated with a decreased overall survival (p &lt; 0.05). Finally, HER3 over-expression, defined as 2+ or 3+ staining, was observed in 52% of the entire cohort and HER3 protein levels exhibited a significant inverse relationship to HER2 protein expression and HER2 gene amplification (p &lt; 0.05). These findings suggest that HER2 and HER3 signaling may function independently of one another in UPSC. The observed alterations in HER2 and HER3 expression levels constitute clinically relevant and prevalent signatures in UPSC that merit further investigation to determine the potential benefits of therapies targeting the epidermal growth receptor pathways.
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 4556. doi:1538-7445.AM2012-4556
Abstract 4558: FDG-PET uptake in breast cancer molecular subtypes
Authors: Elias Sjoerd G. , Wisner Dorota J. , Chen Yunn-Yi , Behr Spencer C. , Griffin Ann , Esserman Laura J. , van't Veer Laura J. , Hylton Nola M. 
Published: August 2012

Abstract
Background: Data on breast cancer FDG uptake in relation to clinically relevant molecular subtypes and their interaction is scarce. Some have shown higher standardized uptake values (SUV) in triple negative (TN) and HER2+ than hormone receptor (HR)+ disease. We hypothesize that FDG uptake in HER2+ disease depends on HR status. Methods: We identified 186 invasive breast cancer patients with a whole body FDG-PET/CT scan between 2005 and 2010 at UCSF (within 6 months prior to or after diagnosis but before therapy). Receptor expression was assessed on adjuvant therapy naïve specimens using IHC (HR [ER and PR], HER2) and FISH (HER2) according to clinical practice. We related routinely assessed (log-transformed) SUVmax to receptor expression with linear regression and analysis of covariance (ANCOVA), and adjusted for tumor grade. Results: SUVmax was reported for 160 primary breast cancers and 154 had complete data for HR and HER2. Median age at diagnosis was 52 years (range 21-87), and 34% had localized, 52% regional, and 14% distant disease. Average tumor size was 3.9 cm (SD 2.2), and 12% had good, 51% moderate and 37% poor grade. FDG uptake strongly depended on molecular subtype (Table). Uptake was lowest in HER2-HR+ and somewhat - but not significantly - higher in HER2+HR- disease. The highest SUVmax was found in HER2+HR+, followed by TN disease (both significantly higher than HER2-HR+). The interaction between HR and HER2 in relation to FDG uptake was significant (P=0.003). ANCOVA showed that the higher TN uptake could largely be explained by differences in grade, whereas SUVmax in HER2+HR+ disease remained significantly higher than in HER2-HR+ disease. Conclusion: This large series of advanced primary breast cancer showed FDG uptake to be comparably low in HER2-HR+ and HER2+HR- disease, but significantly higher in HER2+HR+ and TN disease. Tumor grade largely explained the higher FDG uptake in TN disease but not the results for HER2+HR+. FDG-PET may need evaluation at different settings taking into account uptake variation due to tumor biology.

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 4558. doi:1538-7445.AM2012-4558