bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 433: Role of AQP1 in invasion of GBM
Authors: Samuelson Gay , Feuerstein Burt , Misra Anjan , Bennett Kevin 
Published: February 2011

Abstract
There has been little improvement in glioblastoma multiforme (GBM) patient prognosis over the past 20 years despite advances in imaging, neurosurgery, post-operative care, radiation delivery and chemotherapy. One reason for treatment failure is the highly invasive nature of glioma cells. Thus, it is essential to understand the mechanisms underlying invasion so that therapeutic targets can be developed and their impact assessed, non-invasively, during treatment.
We have identified a trans-membrane protein, Aquaporin 1 (AQP1) whose over-expression correlates inversely with GBM survival (1,2) and drives migration of invading glioma cells (3). Our hypotheses are that the water permeation function of AQP1 drives migration and diffusion-weighted magnetic resonance imaging (DW-MRI) can be used to measure the water permeation and hence, invasion.
The goal of our work is to determine the relationship between AQP1 expression and brain tumor invasion as measured in tissue culture by wound assay, in orthotopic murine brain slices by confocal microscopy and in rodent xenografts by DW-MRI. Modulating aquaporin channels alters water diffusion through cells and these changes have been detected with DW-MRI (4,5).
We have data on 168 GBM patients that shows AQP1 overexpression correlates inversely with survival. Wound assay data indicates AQP1 overexpression drives migration and we have used an inhibitor of AQP1 water permeation, tetraethylammonium chloride (TEA) (6) to show that inhibiting water permeation also inhibits migration, We have histologic data on rodent xenografts demonstrating the aggressive invasive behavior of AQP1 overexpression compared to empty vector controls. We will present preliminary MRI results using an orthotopic rodent model where we modulate levels of AQP1 expression.
References: 1. Verkman AS et al. J Mol Med (Epub), 2008. 2. Nagashima G et al. Brain Tumor Pathol 23(1), 2006. 3. Mirvish et al. Soc Neuro-Onc, 2007. 4. Latour LL. PNAS 91(4), 1994. 5. Thewall PE et al. Magn Reson Med 48(4), 2002. 6. Detmers et al. JBiolChem. 281(20); 14207, 2006.
Supported by the Diane and Bruce Halle Fund, and the Barrow Neurological Foundation
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 433.
Abstract 4343: X-ray detection of hepatocellular carcinoma (HCC) using gold nanoparticles conjugated to HCC-specific SF25 antibodies
Authors: Ortiz Vivian , Derdak Zoltan , Liu Yanan , Diebold Gerald , Wands Jack R. , Rose-Petruck Christoph 
Published: February 2011

Abstract
There is widespread concern among health care professionals regarding the increase in HCC and the lack of optimal detection methods that lead to early diagnosis and treatment. It is hoped that early diagnosis may improve the prognosis of this almost uniformly fatal disease. There are substantial issues with false/negatives and false/positives and better, more specific and sensitive detection methods are urgently needed. For this reason, we aimed to design a novel detection method that is based on phase-sensitive x-ray imaging of gold nanoparticles, conjugated with HCC specific antibodies. Our laboratory has previously established various liver cancer specific antibodies by screening antigens that were uniquely present in the FOCUS hepatocellular carcinoma cell line. In the current study we used the SF25 antibody that is known to cross-react with a 125 kDa cell surface antigen. 10 nm gold nanoparticles were coated with polyacrylic acid (PAA) and poly(allylamine hydrochloride) (PAH), followed by conjugation with the SF25 antibody. The specificity of our antibody was confirmed in vitro by Western-blotting and immunoflurescence using FOCUS and NIH/3T3 cells (negative control). The gold labeling did not interfere with the immunofluorescent detection of SF25 antigen. The cellular localization of the SF25 protein was further confirmed by transmission electron microscopy. A labeling density of 10^4 gold particles per HCC cell was achieved. Given the sensitivity of the phase contrast imaging modality, this labeling density was also sufficient to enhance noticeably the density of subcutaneously raised HCC xenografts in vivo relative to healthy tissue. 10^7 cells were injected in the flanks of athymic nude mice. 1 week after inoculation the tumors were in vivo labeled by gold nanoparticle-conjugated SF25 antibodies. The gold content of these tumors were further quantified by x-ray fluorescence (XRF), which revealed gold fluorescence lines in the x-ray spectrum. These findings suggest that this imaging technique holds high in vivo potential for early detection of HCC. We envision that besides tumor detection, our x-ray imaging modality using nanoparticle-immunolabels will be useful for observing the delivery of drugs attached to or enclosed in nanoparticles.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4343.
Abstract 4344: Virus-templated magnetic nanowires for tumor-targeted imaging
Authors: Ghosh Debadyuti , Lee Youjin , Kelly Kimberly , Belcher Angela 
Published: February 2011

Abstract
In an effort towards early tumor detection, various diagnostic probes, such as tumor marker-specific fluorescent and magnetic nanoparticles, have been developed. Nanoparticles detected using magnetic resonance (MR) imaging is an attractive approach due to its non-invasiveness. Current work has focused on single functionalized spherical nanoparticle systems, one example being cross-linked iron oxide nanoparticles (CLIO). However, these ‘shaped’ particles can be cleared by the reticuloendothelial system upon intravenous injection due to opsonization. Recent work suggests that longer filamentous shaped structures can persist almost 10 times longer in circulation in vivo compared to spherical particles. For clinical diagnostics, it would be desirable to engineer filamentous shaped imaging agents that allow for longer circulation and better homing towards the tumor before immune clearance. M13 filamentous bacteriophage can potentially allow for longer circulation of the imaging agents. Recent work indicates that the virus can circulate in vivo for at least 24 hours compared to the 5-6 hour circulation of various spherical particles (unpublished data).
Using the M13 virus as a scaffold, we can uniquely combine multiple nanoparticles with engineered cell-targeting peptide ligands for tumor-targeted imaging. Exploiting the multiple coat proteins on M13 amenable for peptide display, we have genetically engineered peptides that bind iron oxide nanoparticles (γ-Fe2O3 NPs) and that target secreted protein, acidic and rich in cysteine (SPARC), a protein overexpressed in metastatic prostate and breast cancers. We have been able to assemble monocrystalline, monodisperse γ-Fe2O3 NPs along the virus coat and demonstrate enhanced MR contrast properties, compared to commercially available CLIO. We have investigated specific targeting against prostate cancer in vitro and in vivo. There is a decrease in transverse relaxation times (‘dark contrast’) using targeted nanowires compared to negative control and is specific towards SPARC positive C4-2B cell line compared to DU145 control. SPARC-targeted nanowires were injected intravenously in LNCaP and C4-2B and control DU145 xenograft tumors. MR images indicate dark image contrast in SPARC expressing tumors, compared to control. Histology suggests iron accumulation in the stroma and capsule of SPARC-positive tumors compared to control, suggesting tumor targeting in vivo. These virus-templated probes may have potential as long circulating, targeted non-invasive imaging agents for the early detection of tumors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4344.
Abstract 4355: The C19MC miRNA polycistron are frequent targets of gene amplification in aggressive primitive neuroectodermal brain tumors and encode oncogenic miRNAs that inhibit normal neural stem cell differentiation
Authors: Li Meihua , Lee Kyle , Lu Yuntao , Clarke Ian , Shih David , Meter Tim Van , Zhou Limei , Picard Daniel , Modena Piergiorgio , Pomeroy Scott , Lau Ching C. , Taylor Micheal D. , Bouffet Eric , Rutka James T. , Gajjar Amar , Dirks Peter B. , Hawkins Cynthia E. , Huang Annie 
Published: February 2011

Abstract
Embryonal brain tumors which include medulloblastoma and primitive neuroectodermal brain tumors (CNS-PNET) comprise the largest group of malignant pediatric brain tumors and account for substantial cancer related morbidity and mortality in childhood. Unlike medulloblastoma, a common, cerebellar PNET, few CNS-PNET arising in extracerebellar locations have been characterized. Lack of insight into the molecular pathogenesis of CNS-PNET is a major obstacle towards development of much-needed disease-specific models and treatments for these devastating tumors. In this study, we performed high-resolution DNA copy number analysis on a substantial collection of primary CNS-PNET obtained through an international collaborative group, and discovered a frequent amplicon in 25% (11/46) of CNS-PNET which span 34 protein coding genes and two miRNA clusters, C19MC and miR-371-373, on chr19q13.41. Detailed mapping studies revealed C19MC, which encode 54 primate-specific miRNAs, as the specific target of gene amplification resulting in striking tumor-specific overexpression of a sub-set of miRNAs, including miR-520 g and miR- 517c. Stable expression of miR-520 g and miR-517c promoted in vitro and in vivo oncogenicity and conferred cell survival in tumor cell lines. Strikingly expression of both miR-520g and 517c promoted growth and inhibited differentiation of untransformed normal human neural stem cells. Notably, clinicopathologic analyses revealed that C19MC amplification identifies a distinct group of CNS-PNET with similar gene expression profiles, characteristic histology, and much poorer survival. Our aggregate findings which point to C19MC as an important, new oncogenic locus in a human cancer, have significant implications for the diagnosis and clinical management of embryonal brain tumors in children.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4355.
Abstract 4366: Chronic inflammation in benign prostate tissue is related to the presence of high grade prostate cancer
Authors: Gurel Bora , Lucia Marshall S. , Platz Elizabeth A. , De Marzo Angelo M. 
Published: February 2011

Abstract
Background: Chronic inflammation may be crucial for the etiology of prostatic adenocarcinoma (CaP). If inflammation is part of the pathogenesis of this disease then it might be expected that prostates with adenocarcinoma would harbor more inflammation than prostates without adenocarcinoma.
Design: Cases (biopsy detected and centrally reviewed) and age frequency-matched controls, defined as negative for adenocarcinoma on an end-of-study biopsy, were selected using a nested case-control design from among participants in placebo arm of the Prostate Cancer Prevention Trial (PCPT). The PCPT (n= 18,000 men) determined whether finasteride, a 5-alpha reductase inhibitor, could reduce the period prevalence of adenocarcinoma over 7 years. All men were screened annually by PSA and DRE, and all men not diagnosed with adenocarcinoma during the study were offered an end-of-study biopsy. Cases consisted of 191 men, and controls were from 209 men. Microscope slides (1- 5 core biopsies for each man) were digitized and evaluated online after masking of adenocarcinoma and random benign areas to ensure blinding of the pathologist to case/control status. Inflammation was assessed using a modified National Institutes of Health (NIH) grading system and data were analyzed using logistic regression.
Result: Men who had at least one biopsy core positive for chronic inflammation (CI) (majority was chronic) had 1.79 (95% CI 1.06-3.04) times the risk of prostate cancer compared with no cores positive. The association was stronger for higher-grade (Gleason score 7-10; OR=2.41, 95% CI 1.17-4.95) disease than for lower-grade (Gleason score 6; OR=1.45, 95% CI 0.79-2.68) disease. Risk of prostate cancer (p-trend=0.05) and higher-grade disease (p-trend=0.02) increased with increasing percent of cores positive.
Conclusion: The presence of any chronic inflammation in benign prostate tissue was positively and statistically significantly associated with adenocarcinoma, especially higher grade lesions (Gleason score 7-10). Additional studies to further examine a potential role for inflammation as a cofactor in overall and high-grade prostate cancer should help determine whether chronic inflammation present in benign tissue is a reaction to the presence of cancer, or, is related to the pathogenesis of prostate cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4366.
Abstract 4377: Pulmonary inflammation and lung tumorigenesis in mice
Authors: Keohavong Phouthone , Kahkonen Beth , Kinchington Edwina , Yin Jinling , Jin Jide , Siegfried Jill M. , Di Peter 
Published: February 2011

Abstract
Chronic inflammation has been suggested to be associated with an increased risk of human cancer, including lung cancer, the leading cause of cancer death in the United States. However, the mechanisms of lung tumorigenesis associated with chronic lung inflammation still remain poorly understood. The purpose of this study is to get insight into the molecular mechanisms by which bacterial endotoxin-elicited chronic lung inflammation increases carcinogen-induced lung tumorigenesis. Groups of FBV/N mice were treated weekly for a 15-week period with lipopolysaccharide (LPS), a major pro-inflammatory glycolipid component of the gram-negative bacterial cell wall, with or without a co-treatment of 4-(methyl-nitrosoamino)-1-(3-pyridyl)-1-butanone (NNK), a major component of tobacco smoke and a potent lung carcinogen, during the first four weeks. Analysis of bronchoalveolar lavage fluid (BALF) at one day, one week, and fifteen weeks after LPS-treatment showed a significant increase in pro-inflammatory responses, including both in numbers of macrophages and inflammatory mediators in the mice treated with LPS alone and in those treated with LPS+NNK, compared with the mice treated with NNK alone or those treated with vehicles. These data were confirmed by pathological analysis and the presence of inflammatory cells and lung tissue injury from the groups of mice treated LPS or LPS+NNK, compared with those treated with NNK or vehicles. At week 15, the averaged number of lung tumors per mouse was 5.56 (100% tumor incidence; tumor numbers between 2-9) in mice treated with LPS+NNK and was significantly higher than 0.79 tumor per mouse (67% tumor incidence; tumor numbers between 0-2) in the mice treated with NNK alone (p&lt;0.0001). No lung tumors were observed in the mice treated with LPS or those treated with vehicles alone. Furthermore, a higher proportion of lung tumors from mice treated with LPS+NNK harbored mutations, an GGT to GAT transition, in codon 12 of the K-ras oncogene, compared with the mice treated with NNK alone (76.7% versus 44.4%, p&lt;0.05). Our data show that LPS-elicited chronic lung inflammation increases the risk of NNK-induced lung tumorigenesis in FBV/N mice, and suggest that such an increase occurs mostly through K-ras gene activation pathways.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4377.
Abstract 4378: Aflatoxin B1 inhibits LPS-induced TNF-alpha production in RAW 264.7 cells
Authors: Traore Kassim , Singhal Rohit , Rivera Rachel , Ganey Patricia E. , Roth Robert A. 
Published: February 2011

Abstract
Aflatoxin B1 (AFB1), a potent hepatocarcinogen, is known to impair specific and nonspecific immune responses. Recent studies suggested that AFB1 affects macrophage functions. Macrophages play an important role in a host defense against tumors and bacteria. In addition, some macrophage products, including tumor necrosis alpha (TNF-alpha), can be cytotoxic. In the present study, we investigated the effect of aflatoxin B1 (AFB1) on LPS-induced TNF-alpha production by a mouse macrophage cell line, RAW 264.7 cells. Cells were pretreated with increasing concentrations of AFB1 for 2 hours followed by stimulation with lipopolysaccharide (LPS) for 6 h. The concentration of TNF-alpha released in the culture medium was assessed by enzyme-linked immunosorbent assay (ELISA). AFB1 at 1, 10, 50 or 100 µM reduced the production of TNF-alpha induced by LPS. Compared to vehicle control, there was a greater reduction of TNF-alpha production with increased concentration of AFB1 pretreatment and LPS stimulation. AFB1 at 100 µM decreased the synthesis of both TNF-alpha mRNA and protein in RAW 264.7 cells. To explore the mechanism of AFB1 activation by RAW 264.7 cells, we examined the expression of CYP3A4 and CYP3A11, two isoforms of cytochrome p450 known to activate AFB1. Our data indicated that CYP3A11 but not CYP3A4 was significantly expressed in RAW 264.7 cells. These results suggest that AFB1 pretreatment suppresses LPS-induced TNF production in RAW 264.7 cells. (Supported by NIH grant R01ES04139.)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4378.
Abstract 4381: Biochemical and histopathological evaluation of mice exposed to functionalized single-walled carbon nanotube
Authors: Patlolla Anita K. , McGinnis Britney , Tchouwou Paul 
Published: February 2011

Abstract
Single walled carbon nanotubes (SWCNTs) with their unique physicochemical properties, have many potential new applications in medicine and industry such as sensors, implants or delivery systems. The biomedical application of single-walled carbon nanotubes requires a fundamental understanding of their fate and toxicological profile after administration. However, the toxicity of SWCNT is barely known when they are introduced into the blood circulation, which is especially vital for their biomedical applications. The aim of this study was to conduct biochemical analysis to determine the effect of purified/functionalized single-walled carbon nanotube (SWCNT) on the induction of reactive oxygen species (ROS), activities of specific liver enzymes such as aminotransferases (GOT/GPT), alkaline phosphatases (ALP), concentration of lipid hydro peroxide (LPO) and histopathology of liver, which may be useful as biomarkers of hepatotoxicity and oxidative stress. Three groups of five male mice each weighing approximately 30 + 2 g were injected intraperitoneally once a day for five days with doses of 0.25, 0.5, 0.75 mg/kg BW of functionalized SWCNT. A control group was also made of 5 mice. At the end of the experiment, samples were collected following standard protocols. Exposure to functionalized SWCNT was found to show an increase in the induction of ROS, activities of serum amino-transferases (GOT/GPT), alkaline phosphatases (ALP) and concentration of lipid hydro peroxide compared to control. Histopathological evaluation of liver showed a statistically significant effect in the liver tissue (hepatic fibrosis) compared to controls. The results demonstrate that purified functionalized SWCNT was able to induce hepatotoxicity and oxidative stress. Our result does not imply that CNTs should be banned from use but more in vivo studies with histopathological characterization should be designed in biological application.
Keywords: Single walled carbon nanotube, reactive oxygen species, lipid hydroperoxide, serum aminotransferases, alkaline phosphatases, Swiss-Webster mice, histopathology, hepatotoxicity.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4381.
Abstract 4382: N-acetylcysteine interacts with Cu++ to induce cancer cell death through the generation of hydrogen peroxide
Authors: Zheng Jie , Lou Jessica R. , Benbrook Doris M. , Hanigan Marie H. , Lind Stuart E. , Ding Wei-Qun 
Published: February 2011

Abstract
Metal ionophores that transport copper or zinc into cells are toxic to cancer cells. Loading of metals into cells results in loss of protective intracellular thiols, which can contribute to cell death. We postulated that the metal-thiol interaction might also lead to the generation of cytotoxic compounds. We tested this hypothesis by adding N-acetylcysteine (NAC) to cancer cell lines in the presence of copper or zinc. NAC itself, at concentrations up to 10 mM, was not toxic to a variety of human cancer cell lines, including A2780 (ovarian), MCF-7 (breast), Panc-1 (pancreas), and A375 (melanoma). When added to cells in the presence of Cu++ (3-30 µM), NAC significantly enhanced the cytotoxicity induced by CuCl2 alone. The cytotoxicity of the NAC/copper combination was blocked by the copper-binding compounds tetrathiomolybdate and bathocuproinedisulfonic acid. NAC was not cytotoxic in the presence of zinc. This finding suggested that the redox activity of copper was an important determinant of cytotoxicity and raised the possibility that H2O2 was being generated. This was confirmed in vitro using a colorimetric assay (Biovision). The ability of other thiols to promote H2O2 generation when exposed to Cu++ was then examined. Reduced lipoic acid and L-cysteine generated higher level of H2O2 than NAC did; reduced glutathione was able to generate comparable levels of H2O2 as NAC, while oxidized glutathione generated significantly lower levels of H2O2; oxidized cysteine did not generate H2O2. To determine if H2O2 played a role in the observed cytotoxicity, catalase was added to cells treated with NAC/copper. Its addition completely blocked cell killing, indicating that significant amounts of extracellular H2O2 were being generated. These findings indicate that the interaction of copper with thiols leads to cytotoxic concentrations of H2O2. Thiols may differ in their reactivity with redox active compounds such as copper. Since the copper concentration of plasma is greater than that of tissue culture media, NAC's effects in vivo may differ from those seen in vitro.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4382.