bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4284: Prognosis of prostate cancer using gene expression changes in stroma
Authors: Jia Zhenyu , Rahmatpanah Farahnaz , Chen Xin , Lernhardt Waldemar , Wang Yipeng , McClelland Michael , Mercola Dan 
Published: August 2012

Abstract
Enormous efforts have been invested in the development of biomarkers for prognosis of prostate cancer in order to address urgent questions regarding overtreatment by radical methods. Nevertheless, few accepted and clinically useful biomarkers have been developed. A possible barrier to biomarker discovery may be accumulated genetic alterations in tumor cells resulting in polyclonal/multifocal prostate tumors as well as cell-type heterogeneity of prostate cancer between patients. Tumor-adjacent stroma (tumor microenvironment) is less affected by genetic alteration and might therefore yield more consistent biomarkers for clinical tests. To this end we compared gene expression profiles in stroma near tumor from high-risk patients that chemically relapsed shortly after prostatectomy (&lt; 1 year), and low-risk patients either relapsed later than 4 years after surgery or who did not relapse and had at least 4 years’ follow-up data available. We identified 131 differentially expressed genes in these two categories. We also identified another set of 115 genes of which the expression levels are significantly correlated with time-to-relapse for the relapsed patients. Using the 19 genes that overlapped between the two gene lists, we developed a PAM-based classifier by training on samples containing stroma near tumor: 9 high-risk patient samples and 9 low-risk patient samples. We then tested the classifier on 47 independent samples, including 38 samples containing stroma near tumor and 9 tumor-bearing samples containing at least 90% stroma near tumor. The classifier predicted the risk status of patients with an average accuracy of 87%. These results indicate that the prostate cancer microenvironment exhibits reproducible changes useful for predicting outcomes for patients.
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 4284. doi:1538-7445.AM2012-4284
Abstract 4287: M13-stabilized single-walled carbon nanotubes as nanoprobes for second near-infrared window fluorescent imaging of targeted tumors
Authors: Ghosh Debadyuti , Yi Hyunjung , Qi Jifa , Belcher Angela M. 
Published: August 2012

Abstract
Second near-infrared (NIR) window light (950-1,400 nm) is attractive for in vivo fluorescence imaging due to its deep penetration depth in tissues and low tissue autofluorescence. Here we show genetically engineered multifunctional M13 phage can assemble fluorescent single-walled carbon nanotubes (SWNTs) and ligands for targeted fluorescence imaging of tumors. M13-SWNT probe is detectable in deep tissues even at a low dosage of 2 μg/mL and up to 2.5 cm in tissue-like phantoms. Moreover, targeted probes show specific and four-fold improved uptake in prostate specific membrane antigen positive prostate tumors compared to control non-targeted probes. This M13 phage-based second NIR window fluorescence imaging probe has great potential for specific detection and therapy monitoring of hard-to-detect areas.
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 4287. doi:1538-7445.AM2012-4287
Abstract 4288: in vivo Imaging of early inflammation response in bacterial infection
Authors: Papineni Rao V. , Orton Sean , McLaughlin William , Bianchi Damian 
Published: August 2012

Abstract
Staphylococcus aureus (S. aureus) causes significant morbidity and mortality worldwide and a prime cause in hospital infections. Staphylococcus aureus bactereremia is prevalent in neutropenic cancer patients, and malignancies form a sizeable risk factor for methycillin-resistant S. aureus (MRSA) infections. Targeting the virulence products is a promising approach for developing novel therapeutics. A detailed understanding of the virulence factors and the resultant immune response is quite essential for such development. Here, we established an athymic mice model to assess the initial immune response to S.aureus inoculation. As the polymorphonuclear neutrophils(PMN)and macrophages are a part of the early response, determination of its myeloperoxidase (MPO) activity in vivo is established. MPO is an inflammatory heme protein and utilizes hydrogen peroxide in the process of reactive oxygen species generation. 24 hrs after the intra muscular injection of the S.aureus bacterial lysate, the MPO activity was detected by i.p injection of luminal in mice. The blue luminescence resulting from the MPO activity was imaged and the luminescence images were overlaid on planar X-ray images for anatomical co-registration. The results show a robust MPO activity in the mouse bladder. This increase in MPO activity as a result of neutrophil activation at the bladder region was further confirmed using non-invasive X-ray contrast imaging of the bladder and co-registering the luminescence and the X-ray density signals at the bladder. The initial response shown here has similarities with the mechanism suggested recently for myobacterium bovis bacillus Calmette-Guerin (BCG) treatment of bladder cancer. Bacterial components, its structures that are involved in eliciting the robust PMN infiltration in bladder will be very valuable in the developing better bladder cancer anti-tumor treatments.
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 4288. doi:1538-7445.AM2012-4288
Abstract 4295: Multifunctional nanoconstructs for tumor visualization using contrast enhanced MRI
Authors: Ananta Jeyarama , Sethi Richa , Gizzatov Ayrat , Acharya Ghanashyam , Liu Xuewu , Karmonik Christof , Wilson Lon , Decuzzi Paolo 
Published: August 2012

Abstract
New multifunctional nanoconstructs using mesoporous Si particles (SiMPs) and polymeric hydrogel particles (HG) are synthesized with superior MRI efficacy and favorable pharmacokinetic properties. Clinically relevant Gd3+-based contrast agents (CAs) for magnetic resonance imaging (MRI), namely [Gd (DTPA)]2−, [Gd (DOTA)]1- and superparamagnetic iron oxide (SPIO) nanoparticles, were either i) encapsulated within the mesoporous structure of the SiMPs or ii) covalently attached to SiMPs and HGs. The size (from 400 to 2000 nm) and shape (discoidal, cylindrical, etc.) of the nanoconstructs are accurately tailored during the fabrication process to control the in vivo biodistribution. In tumor bearing mouse model, discoidal particles with a characteristic size of 1000 x 400 nm were found to accumulate at the tumor site more than other particles. The incorporation of clinically used, FDA approved CAs into the mesoporous structure of the SiMPs led to magnetic nanoconstructs exhibiting much higher relaxivities as compared to free CAs in solution. In particular, the relaxivity for [Gd (DTPA)]2− and [Gd (DOTA)]−1 loaded SiMPs was measured to be ∼ 25 mM−1s−1, which is more than 6 times larger than the r1 obtained for free CAs (∼ 4 mM−1s−1). The pore size played a dominant role in that the relaxivity was observed to grow with a reduction in pore diameter: r1 ∼ 24 mM−1s−1 for small pore SiMPs (5-10 nm); and r1 ∼ 10 mM−1s−1 for huge pore SiMPs (30-40 nm). CAs covalently attached to SiMPs and HGs, exhibited no such dependence on pore sizes but provided comparable enhancement in r1. For SPIOs encapsulated in mesoporous SiMPs, a much larger enhancement in relaxivity was observed with r2 ∼ 220 mM−1s−1 for the resulting nanoconstructs against r2 ∼ 11.2 mM−1s−1 for free SPIOs. These results suggest that geometrical confinement into mesopores is a general strategy for enhancing the performance of both T1 and T2 MRI CAs. Intravenous injection of SPIO-loaded SiMPs in melanoma bearing mice decreased the contrast (T2-weigthed relaxation), confirming the high level of accumulation of these nanoconstructs at the tumor site. For the enhanced relaxivity and superior localization of imaging agents at the target site, the proposed nanoconstructs provide an ideal platform for early cancer detection by MRI. In addition, the easily functionalizable surface of these nanoconstructs render them the ability to perform cellular and molecular imaging using clinical MRI scanners.
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 4295. doi:1538-7445.AM2012-4295
Abstract 4301: Shear stress induces Rac1/Rab5 circular ruffling/endosomes at the apical surface of metastatic esophageal tumor cells enhancing spreading and motility responses
Authors: Lawler Karen , Kijanka Gregor , Sullivan Gerald O’ , Long Aideen , Kenny Dermot 
Published: August 2012

Abstract
A coordinated mode of motility is required for dissemination and invasion of esophageal metastases through the vasculature. This motility is largely driven by the activation of GTPases Rac1 and Rab5 which regulate 2 and 3-dimensional motility respectively; however, little is known about the localization and activation of these GTPases under hydrodynamic flow. In this study, the effect of Rac1 activation on tumor motility was investigated in a controlled microfluidic chip that simulates venous flow conditions. A metastatic esophageal cell line derived from the ascites of a male patient with squamous cell cancer of the esophagus (OC-1), was transiently transfected with cDNA encoding active (L61), dominant negative (N17) and wild type (WT) Rac1 fused to GFP to enable visual localization of Rac1 in real time under static and fluid flow conditions. Transfected OC-1 cells were allowed to adhere to fibronectin (Fn) for 30 minutes under static conditions or allowed to adhere to Fn for 5 minutes followed by exposure to a continuous venous shear rate of 200 s-1 for 25 minutes. Cell motility and Rac1 localization was monitored over a 30-minute period followed by cell fixation and co-staining with a polyclonal antibody directed against Rab5 to visualize endosomal trafficking within the cells. The results of our study show that the over-expression of constitutively active Rac1 enhances circular ruffling, pseudopodia formation and motility in OC-1 cells under static conditions when compared to N17 and WT Rac1. Moreover, this activation response in L61-transfected cells is significantly increased in the presence of venous shear rates, (p&lt;0.0013) and completely inhibited in cells expressing the N17 active mutant which display rounded quiescent morphology states. Co-localization studies confirmed that both Rac1 and Rab5 GTPases are recruited to distinct populations of endosomes containing actin at the apical membrane of OC-1 cells under shear, measuring between 0.6 and 1.5 μm. These results suggest that Rab5/Rac1 circular ruffling/endosomal recruitment at the apical surface is an important adaptive response to enhance motility under fluid flow conditions. Moreover, this study may offer insight into mechano-receptor signaling and how metastatic cells adapt and disseminate in circulation.
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 4301. doi:1538-7445.AM2012-4301
Abstract 4303: A high-throughput cell invasion assay combined with reverse phase protein microarrays for rational development of drug combination strategies targeting tumor invasion
Authors: Dawson John C. , Carragher Neil O. , Fronczak Jennifer , Hulkower Keren 
Published: August 2012

Abstract
Tumor invasion and metastasis is responsible for 90% of all deaths in cancer patients that are non-responsive to surgical procedures or initial therapeutic treatments. Clinical studies of inhibitors targeted against specific signalling pathways associated with tumor invasion frequently fail due to alternate signalling pathways that support persistent invasion through compensatory mechanisms. The aim of this study was to apply an image-based multi-well 3-dimensional (3D) invasion assay platform (OrisTM Pro Cell Invasion Assay, Platypus Technologies LLC) incorporating distinct cancer cell types and extra cellular matrix (ECM) substrates in parallel with an ultra-sensitive and high-throughput reverse phase protein microarray (RPPMA) platform (Zeptosens) to identify and validate drugs and their combinations targeting distinct modes of tumor invasion. At sub-micromolar concentrations the results show that a matrix metalloproteinase inhibitor (GM6001) and panel of tyrosine kinase inhibitors suppress the 3D invasion of two breast cancer cell lines (MDA-MB-231 and HCC1569) into a basement membrane matrix. The image based invasion assays further revealed an altered invasive morphology in response to distinct compound treatments, with cells losing their typical elongated mesenchymal phenotype and adopting a more ameoboid shape. These results suggest that inhibitor treatment initiates alternative invasive mechanisms. An RPPMA platform has been used to identify post-translational signalling pathways that drive adaptive responses to monotherapy and to guide selection of drug combination partners. Further testing of drug combinations in the OrisTM 3D invasion assay format shall enable quantification of additive and synergistic drug combination responses upon tumor invasion in parallel with cell viability endpoints. These studies provide a robust model by which to evaluate different combinations of drugs targeting tumor invasion that will help prioritize clinical development strategies. ACKNOWLEDGEMENT: This work was partially supported by NIH Grant 2R44GM090386 to Platypus Technologies.
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 4303. doi:1538-7445.AM2012-4303
Abstract 4308: ZEB1 mediates invasion and chemoresistance of glioblastoma
Authors: Siebzehnrubl Florian , Silver Daniel , Tugertimur Bugra , Deleyrolle Loic , Suslov Oleg , Siebzehnrubl Dorit , Sarkisian Matthew , Kuepper Marius , Yachnis Antony , Brabletz Simone , Brabletz Thomas , Reynolds Brent , Steindler Dennis 
Published: August 2012

Abstract
Despite intense efforts in basic research and clinical medicine, glioblastoma (GBM) remains one of the most lethal types of cancer. In particular, tumor recurrence after surgical resection, aggressive chemotherapy, and targeted radiation remains an insurmountable obstacle. Recurrence has been attributed to residual cancer cells that re-initiate tumor growth after primary clinical intervention. Here, we provide new evidence that a subpopulation of invasive and chemoresistant cancer cells is maintained by the transcription factor ZEB1 (zinc finger E-box binding homeobox 1). ZEB1 is preferentially expressed in invasive glioblastoma cells, and its knockdown results in a dramatic reduction of tumor invasion as well as increased sensitivity to the chemotherapeutic agent Temozolomide (Temodar®, TMZ) in vitro and in vivo. We find that ZEB1 indirectly controls expression of the chemoresistance-mediating enzyme MGMT (O-6-Methylguanine DNA Methyltransferase), as well as cell-cell adhesion pathways, thus linking chemoresistance and brain tumor invasion. Moreover, ZEB1 expression in glioblastoma patients correlates with tumor grade and survival. These results indicate that invasive glioblastoma cells are particularly sheltered from current therapeutic approaches, rendering them likely candidates for tumor recurrence. This offers a potential novel model for GBM recurrence, and a potential new therapeutic target.
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 4308. doi:1538-7445.AM2012-4308
Abstract 4309: DYRK2 regulates cancer invasiveness via Snail/E-cadherin pathway
Authors: Mimoto Rei , Taira Naoe , Yoshida Kiyotugu , Miki Yoshio 
Published: August 2012

Abstract
Epithelial-mesenchymal transition (EMT) is characterized by the loss of cellular adhesion molecule E-cadherin, and plays a fundamental role during early steps of invasion and metastasis. An important regulator of E-cadherin expression is Snail, a zinc-finger transcriptional repressor. Snail is phosphorylated by GSK3-α and then degraded by α-TrCP-mediated ubiquitination. Here we describe another kinase, DYRK2, acts as a priming kinase for snail whose phosphorylation is required for the subsequent GSK3&gamma phosphorylation and proteasomal degradation. Inhibition of DYRK2 expression by siRNA results in up-regulation of Snail and down-regulation of E-cadherin. The expression of fibroblast mrakers, vimentin and fibronectin, emerged in these cells. Furthermore, the invasiveness of MCF7 cells was increased by stable DYRK2 silencing by shRNA. Tumors expressing DYRK2-shRNA robustly formed metastases in nude mice bones, while those expressing control-shRNA little if any. In human breast cancer tissues, DYRK2 exhibits an inverse correlation with the expression of Snail. Conversely, low level expression of DYRK2 is associated with down regulation of E-cadherin. The patiens with tumors expressed low DYRK2 showed significantly poor prognosis and short disease-free survival. These results demonstrate that DYRK2 regulates cancer invasiveness and metastasis via Snail/E-cadherin pathway in human breast 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 4309. doi:1538-7445.AM2012-4309
Abstract 431: ErbB4 is a novel driver of metastasis and anoikis resistance in Ewing's sarcoma
Authors: Mendoza-Naranjo Ariadna , Wai Daniel H. , Farrar Jason E. , Zhu Qingsong , Mistry Priti , Lazic Nikola , Ayala Fernanda Rocha Rojas , Cunha Isabela Werneck da , Arceci Robert J. , Soares Fernando A. , Triche Timothy J. , Strauss Sandra J. , Sorensen Poul Hb 
Published: August 2012

Abstract
Most Ewing family tumor (EFT) related deaths occur as a consequence of metastatic disease. Using high-throughput Affymetrix arrays, and matched primary and metastatic tumor-derived cell line pairs, we have identified ERBB4, a member of the epidermal growth factor receptor (EGFR) family, as a novel driver of metastasis and anoikis resistance in EFTs. Gene expression profiling, mRNA analysis, and immunoblotting revealed a 2 to 4-fold increase in ERBB4 expression in metastatic compared to primary EFT cell lines. SNP profiling failed to show copy number aberrations to explain the increased ErbB4 expression in metastatic cell lines. However, epigenetic mechanisms were found to potentially regulate ERBB4 expression in the paired CHLA-9 primary and in the metastatic/chemoresistant CHLA-10 cell line derived from the same patient. Treatment with 5-aza-2α-deoxycytidine enhanced ErbB4 in CHLA-9 cells, but reduced its expression in CHLA-10, suggesting a potential role for DNA methylation in controlling ERBB4 expression in EFTs. Enhanced protein expression and ErbB4 tyrosine kinase activation were clearly identified in metastatic versus primary cells grown under anchorage independent conditions (as multicellular spheroids), which mimic micrometastases. We next evaluated the clinical relevance of these data using biopsies from EFT patients. We found a direct correlation between ErbB4 expression and reduced disease-free survival (p&lt;0.05), and identified statistically higher ErbB4 expression (p&lt;0.05) in metastatic vs. primary biopsies (80% vs. 56%, respectively). ErbB4 gene knockdown or treatment with the FDA-approved pan-ErbB inhibitor Lapatinib reduced proliferation, blocked cell migration and tumor invasion, and sensitized metastatic/chemoresistant cell lines to EFT standard of care chemotherapeutic drugs. Taken together, our findings identify ErbB4 as a novel driver of metastasis in EFTs.
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 431. doi:1538-7445.AM2012-431
Abstract 4311: EphB2 receptor controls proliferation/migration dichotomy of glioblastoma by interacting with focal adhesion kinase
Authors: Wang Shervin D. , Rath Prakash , Lal Bachchu , Richard Jean-Philippe , Li Yunqing Li , Goodwin C. Rory , Laterra John , Xia Shuli 
Published: August 2012

Abstract
Glioblastoma multiforme (GBM) are the most frequent and aggressive primary brain tumors in adults. Uncontrolled proliferation and abnormal cell migration are two prominent spatially and temporally disassociated characteristics of GBMs. In this study, we investigated the role of the receptor tyrosine kinase EphB2 in controlling the proliferation/migration dichotomy of GBM. We studied EphB2 gain-of-function and loss-of function in glioblastoma-derived stem-like neurospheres (GBM-SCs), whose in vivo growth pattern closely replicates human GBM. EphB2 expression stimulated GBM neurosphere cell migration and invasion, and inhibited neurosphere cell proliferation in vitro. In parallel, EphB2 silencing increased tumor cell proliferation and decreased tumor cell migration. EphB2 was found to increase tumor cell invasion in vivo using an internally controlled dual-fluorescent xenograft model. Xenografts derived from EphB2 overexpressing GBM neurospheres also showed decreased cellular proliferation. The non-receptor tyrosine kinase focal adhesion kinase (FAK) was found to be co-associated with and highly activated by EphB2 expression and FAK activation facilitated focal adhesion formation, cytoskeleton structure change and cell migration in EphB2-expression GBM neurosphere cells. Taken together, our findings indicate that EphB2 has pro-invasive and anti-proliferative actions in GBM stem-like neurospheres mediated, in part, by interactions between EphB2 receptors and FAK. These novel findings suggest that tumor cell invasion can be therapeutically targeted by inhibiting EphB2 signaling and that optimal anti-tumor responses to EphB2 targeting may require the concurrent use of anti-proliferative agents.
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 4311. doi:1538-7445.AM2012-4311