bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5179: Inhibition of U937-cell adhesion to human endothelial cells by glycosylated lysozyme mutants
Authors: Melcher Ralph , Kraus Ina , Demmig Stephanie , Moeller Dorothea , Kudlich Theodor , Rogoll Dorothee , Scheurlen Michael , Scheppach Wolfgang , Hasilik Andrej 
Published: August 2012

Abstract
The evascularization of cells is an important step in defense reactions and the spreading of metastases. During inflammation, the endothelium of the affected tissue becomes activated and interacts with cells bearing cognate structures such as sialyl Lewis X (sLex) substances. In this study, we present the sLex-antagonist hLysII/IV-FUCTVI by which a significant inhibition of adhesion is achieved at 1ng/ml (0.07 nM), making it the most potent known inhibitors of adhesion described to date. In our study we overexpressed the glycosylated human lysozyme mutant hLysII/IV in CHO cells stably expressing fucosyltransferases FUCIII, IV, V, VI, or VII. Digestional analysis with endo- and exoglycosidases showed that hLysII/IV-FUCTVI contains predominantly biantennary complex N-glycans with a variable number of lactosamine repeats; these were terminally sialylated and fucosylated, suggesting the presence of the sLex antigen. In contrast, hLysII/IV-FUCTIII and IV were not terminally sialylated and hLysII/IV-FUCV and VII were not terminally fucosylated. In a static adhesion assay, binding of U937 to activated HUVEC cells was exclusively blocked in the presence of medium supernatant containing hLysII/IV-FUCTVI and by affinity-purified hLysII/IV-FUCTVI.
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 5179. doi:1538-7445.AM2012-5179
Abstract 5260: Genomic gains in prostatic carcinoma and proliferative inflammatory atrophy in dogs
Authors: Alves Carlos E. Fonseca , Busso Ariane F. , Silveira Sara M. , Rogatto Silvia R. , Amorim Renee Laufer 
Published: August 2012

Abstract
The dog can spontaneously develop prostate cancer and consequently can be used as an experimental model for prostatic diseases associated with aging, including benign prostate hyperplasia (BPH) and prostate carcinoma (PCa). DNA copy number variations (CNVs) have been used to identify genes associated with cancer development and progression. DNA microarray based comparative genomic hybridization (aCGH) is a technique that allows to identify copy number of thousands of genes throughout the genome. aCGH was used to identify genomic regions with significantly different DNA copy number in three benign prostatic hyperplasia (BPH), four proliferative inflammatory atrophy (PIA), and 14 canine prostate carcinoma (PCa). Five histologically normal prostate tissue were used as reference. Genomic DNA was extracted from formalin fixed and paraffin embedded samples and CNVs data was evaluated in Canine Genome CGH Microarray 4x44K (G2519F, Design ID021193, Agilent). Data analysis was performed using Genomic Workbench Standard Edition 5.0.14 (Agilent). PCa showed higher number of altered genes related to canonical diseases process, cellular functions and molecular pathways as well as greater inter-relationship between genes, compared with PIA and BPH. In conclusion, PCa showed a more complex genotype, being losses the most frequent genomic changes. Some discrepancies between genomic alterations in human and canine carcinomas may indicate the different clinical behavior of these tumors in these two species. In addition, it was observed was an ascending pattern of genomic complexity in BPH, PIA and CA consistent with a model of multistep tumor progression.
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 5260. doi:1538-7445.AM2012-5260
Abstract 5282: Leptin induces Notch in endothelial cells: Role of VEGFR-2 transactivation
Authors: Lanier Viola , Gillespie Corey , McGlothen Tanisha , Dickson Toi , Guo Shanchun , Gonzalez-Perez Ruben R. 
Published: August 2012

Abstract
Notch signaling is essential for breast cancer (BC) angiogenesis and its dysfunction is implicated in many cancers. Leptin (a pro-angiogenic, pro-inflammatory and mitogenic factor) induces the expression of VEGF/VEGFR-2 and Notch in BC cells. Moreover, the binding of leptin to its receptor (OB-Rb) in endothelial cells (EC) was shown to phosphorylate/transactivate VEGFR-2 inducing angiogenic features. We hypothesize that leptin is an inducer of Notch in EC and that this effect could occur upon leptin-mediated transactivation of VEGFR-2, thereby inducing angiogenic changes in EC. To this end, HUVEC cells were challenged with leptin, leptin inhibitor (LPrA2) VEGFR-2 kinase inhibitor (SU5416) and Notch signaling inhibitor (DAPT). Leptin-dose and time-course effects on expression of Notch (receptors: Notch1, Notch2, Notch3 and Notch4; ligands: JAG1, Dll-4 and targets: survivin and Hey2) were determined by WB and real time RT-PCR. The impact of LPrA2, SU5416 and DAPT on leptin-induced VEGFR-2 phosphorylation and Notch expression was also determined. The effects of leptin and inhibitors on EC proliferation, migration and tube formation were investigated. Results from our studies show for the first time that leptin is a potent inducer of Notch signaling in EC. Moreover, leptin-induced VEGFR-2 phosphorylation was closely related to leptin effects on Notch and the angiogenic features of EC. Therefore, leptin secreted either by adipose tissue or BC cells may contribute to tumor angiogenesis by acting directly on cancer cells inducing VEGF secretion or through EC inducing VEGFR-2/Notch crosstalk. Present results underline the notion that combinatory therapies targeting both Notch and leptin signaling could be a new strategy for BC treatment. [This work was supported in part by NIH/NCI1SC1CA138658-02; NIH/ARRA/3SC1CA138658-02S1 and the Georgia Cancer Coalition Distinguished Cancer Scholar Award (to RRGP)].
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 5282. doi:1538-7445.AM2012-5282
Abstract 5283: Autophagy regulation of angiogenesis in human neuroblastoma
Authors: Kim Kwang Woon , Chung Dai. H 
Published: August 2012

Abstract
Neuroblastoma is a progressive solid tumor in infants and children that originates from neural crest and it remains a clinical challenge to treat. It is a highly malignant tumor, in part, because angiogenesis is a key factor in tumor progression of neuroblastoma. We have previously identified that gastrin-releasing peptide (GRP)-receptor-mediated cell signaling is critical to its tumorigenicity. In this study, we hypothesized that increased autophagy via blockage of GRP receptor could potentially inhibit angiogenesis in human neuroblastomas. METHODS. Autophagic key molecular markers were detected with ATG5, Beclin-1 and LC3 antibodies. Phosphorylation of Akt, mTOR and S6R were detected by Western blotting. Angiogenesis were measured using tubule formation of human umbilical vein endothelial cells (HUVECs) grown on top of Matrigel Matrix Basement Membrane in vitro. They were also determined using a mouse model of the cornea pocket assay in vivo. Autophagy was determined by punctuate localization of GFP-LC3 fusion protein, and observed under a confocal fluorescence microscope in vitro. RESULTS. Levels of phospho-Akt, -mTOR and -S6R were increased in BE(2)-C cells treated with GRP in both time- as well as dose-dependent manner. However, the PI3K/Akt/mTOR pathway was inactivated in short-hairpin (sh) silenced targeted at GRP receptor in BE(2)-C cells when compared to control shLac cells, indicating that angiogenesis may be reduced. We also observed increased levels of ATG5, Beclin-1 and LC3 proteins, key autophagic mediators, in shGRP receptor-BE(2)-C cells when compared to controls (shLac cells). In particular, overexpression of ATG5 and Beclin-1 also significantly decreased tube formation on HUVECs when treated with exogenous GRP (100 nM). Consistent with the in vitro findings, treatment with GRP receptor antagonist (RC3095) showed a dramatically decrease in angiogenesis in a mouse model of the cornea pocket assay in vivo. CONCLUSIONS. Our results show that enhanced autophagy was associated with a downregulation of angiogenesis signaling pathways, and an increase in characteristic punctuate localization of GFP-LC3 as a marker for autophagy. A better understanding of how autophagic proteins can regulate the angiogenic process may lead to novel therapeutic strategies in the treatment of neuroblastomas or its vascular disorders.
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 5283. doi:1538-7445.AM2012-5283
Abstract 5304: RNA sequencing of circulating tumor cells implicates WNT signaling in pancreatic cancer metastasis
Authors: Yu Min , Ting David T. , Stott Shannon L. , Wittner Ben S. , Ozsolak Fatih , Paul Suchismita , Ciciliano Jordan C. , Smas Malgorzata E. , Gilman Anna J. , Ulman Matthew J. , Contino Gianmarco , Alagesan Brinda , Brannigan Brian W. , Milos Patrice M. , Ryan David P. , Sequist Lecia V. , Bardeesy Nabeel , Ramaswamy Sridhar , Toner Mehmet , Maheswaran Shyamala , Haber Daniel A. 
Published: August 2012

Abstract
Circulating tumor cells (CTCs) shed into blood from primary cancers include putative precursors that initiate distal metastases. While isolation and molecular analysis of these cells is technically challenging, they may identify cellular pathways that contribute to the blood-borne dissemination of cancer cells. Here, we adapted a microfluidic device for efficient capture of CTCs from an endogenous mouse pancreatic cancer model and subjected CTCs to digital gene expression (DGE) analysis using single molecule RNA sequencing. We identified Wnt2 as enriched in both CTCs and metastatic ascites cells, compared with primary tumors. Expression of Wnt2 in pancreatic cancer cells suppresses anoikis, enhances anchorage-independent sphere formation, and increases metastatic propensity in vivo. The effect of Wnt2 is correlated with fibronectin upregulation, and it is mediated in part through non-canonical Wnt signaling and suppressed by inhibition of the Map3k7 (Tak1) kinase, an integrator of Wnt, BMP and TGF-β signaling. DGE analysis of human pancreatic CTCs reveals significant enrichment for non-canonical Wnt signaling in 5 of 11 cases, with Wnt2 RNA detectable by in situ hybridization in a subset of CTCs. Identifying CTC-enriched transcripts such as Wnt2 may point to pathways that enhance haematogenous metastasis, thus providing novel therapeutic targets to prevent the distal spread of 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 5304. doi:1538-7445.AM2012-5304
Abstract 5310: Regulation of metastatic breast cancer by E2F transcription factors
Authors: Andrechek Eran R. 
Published: August 2012

Abstract
Metastasis is the leading cause of mortality in breast cancer and the purpose of this study was to examine the role of the E2F transcription factors in mediating the dissemination of the primary cancer. E2F transcription factors have previously been demonstrated to play a critical role in regulation of cell cycle progression. However, in prior work we have demonstrated that gene expression signatures for the E2Fs have variable levels of activation in a heterogeneous tumor model. Using predictive bioinformatic methods to assess the probability of gene pathway activation, we have predicted variable roles for the E2Fs in key mouse models of breast cancer, including Myc, PyMT and Neu. We then genetically tested these computational predictions by interbreeding E2F knockout mice to the various transgenic tumor models. These crosses have revealed that the E2Fs have unique roles in tumor initiation and progression depending upon the oncogene driving the initial tumor. There are differential effects on tumor latency with the loss of individual E2F alleles, including decreased latency with E2F2 loss in the PyMT background but increased latency and reduced incidence in the Myc background. Moreover, we have observed key differences in tumor progression, with loss of E2Fs affecting the heterogeneity of the resulting tumors. In addition to tumor initiation, we have observed striking differences in tumor progression with loss of E2Fs increasing metastasis in the Myc model but reducing metastasis in the PyMT model. In order to determine the mechanism of action for these effects, we have undertaken a gene expression analysis from both primary tumors and the metastases. Comparison of tumor models in the various backgrounds has allowed us to generate a list of E2F target genes that have effects on metastasis. Comparison of these genes to human breast cancer has revealed that the key genes also have critical roles in metastatic human breast cancer survival. These E2F targets include genes that have previously been identified as metastasis suppressors and are being validated in this process. Taken together, this work suggests a critical role for the E2F transcription factors, not only as mediators of cell cycle but in regulating the metastatic progression of metastatic breast cancer. These data also illustrate the power of combining various genomic and gene expression analysis techniques with both mouse models and clinical data associated with gene expression analysis in human breast cancer. Using this approach we are able to predict and test for the role of critical pathways, such as the E2Fs, in the progression of 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 5310. doi:1538-7445.AM2012-5310
Abstract 5375: Modulation of circulating regulatory T-cells and MDSCs in high risk melanoma patients treated with neoadjuvant ipilimumab
Authors: Tarhini Ahmad A. , Edington Howard , Butterfield Lisa H. , Moschos Stergios , Tawbi Hussein , Shuai Yongli , Shipe-Spotloe Janice , Simonetta Margaret , Johnson Jonas T. , Kirkwood John M. 
Published: August 2012

Abstract
Background: Melanoma regional lymph node and in-transit metastases (stage IIIB-C) carry a high relapse and mortality risk. Neoadjuvant ipilimumab may modulate the host suppressor immune response, enhance antitumor immunity and improve the clinical outcome. Methods: Patients with clinically palpable stage IIIB-C melanoma were treated with induction ipilimumab (10 mg/kg IV q3weeks x2doses) preoperatively and had definitive lymphadenectomy (week ≥ 6), followed by 2 maintenance doses of ipilimumab (q3 weeks). Tissue samples were obtained at baseline and at definitive surgery (after 2 doses of ipilimumab) and blood (serum/PBMC) collected at baseline, 6 weeks, then at 3, 6, 9, 12 months and/or progression. Circulating T-regulatory cells (T-regs) and myeloid derived suppressor cells (MDSC) were monitored utilizing multicolor flow cytometry comparing preoperative (6 weeks) and baseline samples. Results: Twenty nine patients (20 male, 9 female), age 40-87 (median 54) have been enrolled since February/2010 (24 cutaneous primary, 1 unknown and 4 mucosal). Five had AJCC stage IIIB (N2b, N2c) and 24 had IIIC (N3) melanoma. Ninety one cycles have been delivered (median 4). Grade 3 (worst) toxicities include diarrhea/colitis (5 patients; 17%), hepatic enzyme elevations (2; 7%), rash (2; 7%), lipase (1; 3%), all manageable. Median follow-up is 9.7 months and 18 patients (62%) continue disease free. Median PFS is 15.5 months, 95% CI = (8.1, -). The probability of 6 and 12 months PFS is 84.2% (95% CI=0.63, 0.94) and 54.1% (95% CI=0.31, 0.73) respectively. There is a significant increase in the frequency of circulating T-regs (CD4+CD25hi+ Foxp3+; p=0.023 CD4+CD25hi+CD39+; p=0.001) from baseline to 6 weeks. In parallel there is a significant decrease in circulating MDSCs: (1) monocytic: HLA-DR+/low/CD14+; p=&lt;.0001 and less significantly for (2) other monocytic: lin1neg/HLA-DRneg/CD33+/CD11b+; p=0.198 and (3) lymphoid: Lin1neg/HLA-DR-/CD33+/CD11b+; p=0.338. Conclusions: Neoadjuvant ipilimumab is clinically promising and significantly downregulates MDSCs which appear to play a significant role in the clinical activity of ipilimumab. T-regs are upregulated as part of the overall CD4+ T-cell population, and functional studies of this population are ongoing.
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 5375. doi:1538-7445.AM2012-5375
Abstract 5378: Phase I trial of EUS-guided intratumoral vaccination with recombinant Panvac-F and systemic Panvac-V in patients with locally advanced pancreatic cancer
Authors: Poplin Elizabeth A. , August David A. , Ben-Menachem Tamir , Michael Hazar , Artymyshyn Renee , Gulley James L. , Schlom Jeffrey , DiPaola Robert S. , Lattime Edmund C. 
Published: August 2012

Abstract
Preclinical studies in our laboratory were the first to demonstrate the superiority of intratumoral poxvirus vaccines in overcoming immune escape and effectively treating murine solid tumor models. Murine models of bladder and orthotopic mammary tumor demonstrated anergy to systemic immunization using antigen encoding vaccinia recombinants while responding to immunization into the tumor microenvironment. We present here the translation of these findings to a Phase I trial in six patients with locally advanced inoperable adenocarcinoma of the pancreas (NCT00669734). The first dose cohort of patients were treated using a combination of EUS-guided intrapancreatic tumor injection of recombinant Panvac-F (Fowlpox encoding MUC-1, CEA, TRICOM, 108 PFU) in addition to systemic Panvac-V (vaccinia, 2 X 108 PFU) and Panvac-F (109 PFU) boosts (accompanied by subcutaneous rH-GM-CSF, 100 mcg X 4 days). Patients received a total of 2 intrapancreatic injections of Panvac-F (2 weeks apart) with systemic Panvac-V and Panvac-F boosts given with GMCSF extending to day 71 (total of 2 intrapancreatic Panvac-F, 1 sc Panvac-V, 4 sc Panvac-F). Patients were allowed to transition to standard care at day 35. Patients were evaluated for toxicity, tumor progression, and serum CA 19-9 and CEA levels. Two of six patients were removed from study after approximately two weeks due to rapid disease progression and died one and six months after trial initiation. Of the remaining four, one had received prior treatment with gemcitabine followed by capecitabine and radiation and received no further treatment after vaccination; three received post-vaccination standard treatment with gemcitabine. Of the 4 patients with followup of greater than 6 mos, all have stable disease with no progression to metastasis (19 mos, 17 mos, 16 mos, 13 mos). One pt had a DLT (pancreatitis) that resolved allowing completion of protocol therapy. Results demonstrate that the “first in human” intrapancreatic administration of recombinant poxvirus was well tolerated with the complete regimen suggesting an encouraging period of stable disease. The trial is currently accruing patients at intrapancreatic dose level 2 (109 PFU). This study is supported by the NCI Cancer Therapeutics Evaluation Program (CTEP) and by NCI U01-CA07031 and P30-CA72720.
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 5378. doi:1538-7445.AM2012-5378
Abstract 5379: Combination treatment with Bevacizumab, Lenalidomide, Docetaxel and Prednisone (ART-P) does not impact the immune response in patients with metastatic castration-resistant prostate cancer
Authors: Jochems Caroline , Tucker Jo A. , Poole Diane J. , Beatson Melony , Mulquin Marcia , Madan Ravi A. , Figg William D. , Dahut William L. , Gulley James L. , Schlom Jeffrey , Tsang Kwong-Yok 
Published: August 2012

Abstract
Purpose: Investigation of the effect of combination therapy for 5 cycles with bevacizumab, lenalidomide, docetaxel and prednisone (ART-P) on the immune response in patients with metastatic castration-resistant prostate cancer (mCRPC). The aim was to ascertain if treatment containing prednisone and docetaxel would impact immune responses, which could compromise the efficacy of subsequent immunotherapy. Experimental Design: We report here a study of immune responses in 12 patients enrolled in a phase II trial of ART-P at the National Cancer Institute (NCI). We compared peripheral blood mononuclear cells (PBMC) and serum samples collected at baseline and post 5 3-week cycles of ART-P treatment. PBMCs were analyzed using flow cytometry to characterize phenotypes of T-cells, regulatory T-cells, myeloid derived suppressor cells (MDSC) and natural killer (NK) cells, and T-cell proliferation as well as NK-cell functional activity were evaluated. Serum samples were analyzed for levels of cytokines, chemokines and vascular endothelial growth factor (VEGF) with ELISA assays. Results: The baseline characteristics for the 12 patients were: median age 65.7 years, Gleason score 8, and PSA 74 ng/ml. Greater than 50% decreases in PSA were seen in 9/12 patients, with a median decrease of 74%. Of the 12 patients 7 had a partial response, and 5 had stable disease by RECIST criteria. After 5 cycles of ART-P treatment we found no significant differences from baseline in T-cell proliferation and NK-cell function, or the frequencies of T-cells, regulatory T-cells, MDSC and NK-cells. There was also no change in the serum levels of cytokines and chemokines except for IL-6, which decreased. As expected, the serum levels of VEGF substantially decreased with therapy. Conclusions: Treatment of mCRPC patients with ART-P for 5 cycles did not alter the immune response in a way that would decrease the likelihood of successful immunotherapy, pre or post treatment with ART-P.
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 5379. doi:1538-7445.AM2012-5379