bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-420: Long circulating 18F-labeled liposomes for PET imaging
Authors: Xu Biying , Basuli F , Wu H , Salima A. , Opina A , Lane K , Griffiths G. L. , Jagoda E. , Green M , Seidel J. , Choyke P. 
Published: August 2012

Abstract
Liposomes are lipid nanoparticles comprised of phospholipid bilayers with an aqueous interior. They have emerged as promising multi-modality imaging agents and engender significant interest as drug delivery vehicles, e.g. doxorubicin liposomes. Although a number of methods for radiolabeling liposomes with various radionuclides have been developed, 18F is the most useful for PET imaging. In this study, preformed maleimide-PEG functionalized liposomes with a mean diameter of 70 nm were obtained by sonication of a lipid mixture consisting of DPPC, cholesterol, and DSPE-PEG2000-Mal (61:30:9) in acetate buffer (pH 6.5) followed by extrusion. 18F labeled 2-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)ethanethiol was prepared, followed by conjugation with the maleimide-PEG functionalized liposome in 0.1M acetate buffer (0.1% EDTA), pH 6.5-8.0. Liposome sizes did not differ significantly before and after the 18F labeling. The overall radiochemical yield of the reaction was 10-25% (n= 12, uncorrected) in a 180 minute radiolabeling time. Micro PET imaging of rats was done at various times, up to 4 hrs, following IV injection of the 18F liposomes and their bio-distribution was also investigated. Our imaging studies with 18F liposomes appear comparable to images from previously described labeling methods with 18F liposomes remaining in the blood pool at 4 hrs. Our results indicate that this will allow the ready availability of 18F liposomes for vascular imaging and also potentially for cancer imaging. Research Support: This study was funded by the intramural program of the National Institutes of Health.
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 LB-420. doi:1538-7445.AM2012-LB-420
Abstract LB-80: Role of ER calcium in Bcl-2 resistance to dosage and duration-related cytotoxic efficacy of Taxol
Authors: Pan Zhi , Gollahon Lauren 
Published: August 2012

Abstract
Background and Objectives: Calcium is one of the key regulators in apoptosis. Among various calcium sources, our previous study shows that the endoplasmic reticulum (ER), the main intracellular calcium storage site, provides a specific target for the chemotherapy agent Taxol and thus contributes to apoptosis. Although the expression of the anti-apoptotic protein Bcl-2 has been shown to confer resistance to Taxol, the exact mechanism of how it inhibits apoptosis and the role of ER calcium in this process remains unclear. This study investigated whether ER-associated calcium changes were generated and related to resistance by Bcl-2 to Taxol-induced apoptosis. Materials and methods: Fluo4-AM and Cameleon D1ER was used to monitor cytosolic and ER calcium dynamics by advanced time-lapsed imaging. Annexin V-FITC and propidium iodide were used to detect various phases of apoptosis induced by Taxol at different dosages from 10−12 to 10−5 M and at different durations from 5 min to 12 hours. Breast cancer cell lines MDA-MB-M468 and MDA-MB-231 were used and Bcl-2 transfectant cell lines were constructed by stable transfection. Results and Significance: Our previous data shows that Taxol (above 10−6 M) induces a rapid ER calcium release (peaking at 5 minutes) that promotes apoptosis. In this study, upon the expression of Bcl-2, basal ER calcium levels are decreased and Taxol-induced ER calcium release is inhibited, playing a major role in Bcl-2 resistance to Taxol. Depending upon dose and exposure time, long-term (hours) Taxol treatment partially overcame the Bcl-2 inhibition of ER calcium release by continually stimulating the ER calcium release, ultimately inducing significant, although smaller apoptosis in the presence of Bcl-2 expression. In addition to the effect on ER calcium, our data shows that the extracellular calcium pool is involved in Bcl-2 resistance through increased capacitative calcium entry to refill the ER calcium store, preventing ER calcium depletion. Taxol does not have a significant effect on the enhanced calcium influx from the extracellular medium. Taken together, out results indicate that the ER calcium store is the focus of the Taxol attack and plays a key role in Bcl-2 resistance to cytotoxic efficacy of Taxol in breast cancer cells. This finding provides insight to better understand the complex relationship between Bcl-2, calcium and Taxol towards improving breast cancer chemotherapies.
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 LB-80. doi:1538-7445.AM2012-LB-80
Abstract LB-91: Transcriptome analysis of esophageal squamous cell carcinoma by SAGE identifies a new biomarker, NRD1
Authors: Uraoka Naohiro , Sakamoto Naoya , Oue Naohide , Sentani Kazuhiro , Anami Katsuhiro , Noguchi Tsuyoshi , Yoshida Kazuhiro , Yasui Wataru 
Published: August 2012

Abstract
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide. Because most ESCC is diagnosed at advanced stages, the overall 5-year survival rate of ESCC still remains low in spite of the use of various treatment modalities. Therefore, identification of new diagnostic markers and therapeutic targets for ESCC is important. Serial Analysis of Gene Expression (SAGE) is one of the common comprehensive methods to analyze transcript expression levels, and enables the quantitative and simultaneous analysis of a large number of transcripts. To identify potential diagnostic markers and therapeutic targets for ESCC, the SAGE library was generated from one ESCC sample. A total of 14,430 tags were generated, including 5,765 that were unique. By comparing SAGE tags from the ESCC sample with those from normal human squamous esophagus, several genes that is upregulated in ESCC compared with normal squamous esophagus in ESCC were identified. Among these, we focused on the nardilysin (N-arginine dibasic convertase, NRD1) gene. NRD1 has been reported to be associated with ectodomein shedding of TNF-α through activation of ADAM proteases. There is only one report in the literature mentioning the association of NRD1 with cancer (breast cancer), however, there is no report that links expression of NRD1 and ESCC. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis showed a high level of NRD1 expression in three of five esophageal cancer cell lines and seven of 14 ESCC samples, but not in 14 normal systemic tissues. Western blot analysis also showed upregulation of NRD1 protein in total five esophageal cancer cell lines. Immunohistochemical analysis revealed expression of NRD1 in cytoplasm of 43 out of 109 ESCC cases (39%), as well as heart, skeletal muscle, and testis in agreement with previous reports. In clinicopathological analysis, expression of NRD1 correlated with the advanced T grade, N grade and tumor stage, and was an independent predictor of survival in patients with ESCC. Knockdown of NRD1 in TE5 cells inhibited cell invasion ability. Furthermore, qRT-PCR analysis showed a reduction of matrix metalloproteinase-2 (MMP-2) expression in NRD1 knocked down cells. In conclusion, NRD1 is an independent predictor of survival, and contribute to cell invasion through regulation of MMP-2 in ESCC. NRD1 could be a novel diagnostic and therapeutic target for ESCC.
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 LB-91. doi:1538-7445.AM2012-LB-91
Abstract LB-99: EGF receptor tyrosine kinase defines critical prognostic genes of stage IA lung adenocarcinoma
Authors: Nakata Asuka , Yamauchi Mai , Yamaguchi Rui , Kohno Takashi , Nagasaki Masao , Shimamura Teppei , Imoto Seiya , Saito Ayumu , Ueno Kazuko , Hatanaka Yousuke , Yoshida Ryo , Higuchi Tomoyuki , Nomura Masaharu , Beer David G. , Yokota Jun , Miyano Satoru , Gotoh Noriko 
Published: August 2012

Abstract
Non-small cell lung cancer (NSCLC) is the commonest and the most fatal histological subtype of lung cancer. About 10-30% of patients diagnosed as stage IA (the earliest stage of a lung tumor, smaller than three centimeters in diameter with no evidence of regional lymph node and/or regional metastasis) and submitted to surgery die due to recurrence. Therefore, the identification of prognostic biomarkers for stage IA lung adenocarcinoma with poor prognosis is of great importance to select patients who will be benefited by adjuvant therapy. To the best of our knowledge, there is not a set of genes that identifies these patients. It is known that epidermal growth factor (EGF) signaling pathway is closely related to aggressive phenotypes of lung and other cancers. EGFR tyrosine kinase-specific inhibitor, namely gefitinib is expected to alter the gene expression patterns caused by EGFR tyrosine kinase activity. We performed microarray assays in order to obtain the entire gene expression time course profile of human primary lung epithelial cells that were stimulated with EGF in both the presence and absence of gefitinib. The time courses are composed of 19 time points along 48 hours. The data were subjected to a mathematical analysis, namely the State Space Model (SSM) in order to select genes with gene expressions altered by gefitinib. One hundred thirty nine genes were identified. These genes were used as expression signatures to train a risk scoring model that classifies patients in high- or low-risk (risk of dying in five years). This model was trained by using a data set composed of 253 North American patients with lung adenocarcinomas. Then, the predictive ability of the risk scoring model was examined in two independent cohorts composed of North American and Japanese patients. The model enabled the statistically significant identification of high-risk stage IA lung adenocarcinoma in both cohorts, with hazard ratios (HRs) for death of 7.16 (P=0.029) for North American and 10.98 (P=0.008) for Japanese. The set of 139 genes altered by gefitinib includes several ones that are involved in biological aspects of cancer phenotypes but are yet unknown to be involved in EGF signaling. This result strongly re-emphasizes that EGF signaling status underlies aggressive phenotype of cancer cells, and also suggests the first set of genes that are useful for the identification of stage IA lung adenocarcinoma patients with poor prognosis.
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 LB-99. doi:1538-7445.AM2012-LB-99
Abstract PL02-03: Genomic mapping of cancer origins
Authors: Gilbertson Richard J. 
Published: August 2012

Abstract
Cancer comprises a bewildering assortment of diseases that kill 7.5 million people each year. Poor understanding of cancer's diversity currently thwarts our goal of a cure for every patient, but recent integration of genomic and stem cell technologies promises a route through this impasse. In particular these studies have provided new insight into the origin of cancer subgroups currently regarded and treated as single diseases. The improved understanding of tumor biology and accurate preclinical models derived from these studies hold promise to advance cures for all patients with 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 PL02-03. doi:1538-7445.AM2012-PL02-03
Abstract SY02-01: Targeting the histone methyltransferase DOT1L in MLL-rearranged leukemia
Authors: Richon Victoria M. 
Published: August 2012

Abstract
Protein methyltransferases (PMTs) are enzymes that catalyze the addition of methyl groups to the lysine and arginine residues of proteins, including histones. Recent evidence shows that PMTs are misregulated in a variety of cancers and thus may serve as therapeutic targets. A subset of acute leukemias have reciprocal translocations at 11q23 involving the PMT gene mixed lineage leukemia (MLL). MLL translocations occur in approximately 5% of adult acute lymphocytic leukemias (ALL) and 5 to 10% of adult acute myeloid leukemias (AML) including therapy-related leukemias. Multiple studies have demonstrated that patients with leukemias bearing the MLL translocation have a poor prognosis and are in need of new therapies. Translocations of the MLL gene result in the loss of the catalytic domain of the protein. The most common translocation partners, AF4, AF9 and ENL, recruit another PMT, DOT1L that methylates histone H3K79. Recruitment of DOT1L to the MLL fusion protein results in increased H3K79 methylation at MLL fusion protein target genes and elevated expression of the MLL target genes resulting in leukemogenesis. Mistargeted DOT1L enzymatic activity has therefore been proposed to be required for the development and maintenance of leukemias bearing the MLL translocation. To evaluate the potential of DOT1L as a therapeutic target in MLL- rearranged leukemia, we designed and characterized the DOT1L inhibitor EPZ004777, a small molecule with sub-nanomolar affinity for this enzyme and &gt;1000 fold selectivity against other PMTs. EPZ004777 selectively inhibits intracellular histone H3K79 methylation in a concentration and time dependent manner. Significant changes in genes expression were observed in MLL-rearranged cell lines following the decrease in histone H3K79 methylation. Gene set enrichment analysis (GSEA) of genes downregulated following EPZ004777 treatment demonstrated strong enrichment for genes overexpressed in MLL-rearranged human acute leukemias as compared with MLL-germline acute leukemias. Phenotypically, EPZ004777 inhibits proliferation and induces apoptosis in human MLL-rearranged leukemia cell lines, with little effect on non-MLL-translocated cells. In vivo administration of EPZ004777 leads to extension of survival in a mouse MLL xenograft model. These studies provide compelling validation for the development of DOT1L inhibitors as targeted therapeutics for MLL-rearranged leukemia.
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 SY02-01. doi:1538-7445.AM2012-SY02-01
Abstract SY05-02: Novel roles for microRNAs in metastatic progression
Authors: Tavazoie Sohail 
Published: August 2012

Abstract
Metastasis is the major cause of death for cancer patients. This fact highlights the importance of committing significant research efforts to the elucidation of the molecular mechanisms underlying metastatic progression. We had previously investigated the mechanisms by which post-transcriptional mechanisms regulate metastatic gene expression. By using an in vivo selection mouse system that recapitulates human breast cancer metastasis in conjunction with a systematic and functional approach, we previously identified the first set of metastasis suppressor microRNAs (miR-335, miR-126, and miR-206), which strongly suppress human breast cancer metastasis to bone and lung of mice. These small non-coding RNAs are silenced in metastatic cell lines and in human metastatic primary breast cancer cell populations; they are also prognostic biomarkers in that their silencing in primary tumors of patients correlates with the likelihood of metastatic free survival in patients. Since our findings, a number of investigators have implicated these miRNAs in suppression of cancer progression in additional cancer types as well as silencing of these miRNAs in additional cancers. Also, many other microRNAs have been identified by the research community with metastasis suppressive capacities. Our group has focused our efforts on characterizing both the mechanisms by which miR-335, miR-126, and miR-206 mediate metastasis suppression as well as the mechanisms by which the expression of these molecules are silenced in highly metastatic cells. By applying an integrative experimental approach, we have begun delineating the molecular mechanisms by which these miRNAs suppress metastatic progression. While miR-335 acts cell-autonomously to suppress metastatic invasion and migration, miR-126 acts non-cell autonomously to modulate the recruitment of endothelial cells to breast cancer cells. We find that highly metastatic cells recruit mature endothelial cells with higher efficiency than poorly metastatic cells. MiR-126 suppresses endothelial recruitment by cancer cells through targeting of a novel set of pro-metastatic and pro-angiogenic genes that correlate in expression with human metastatic relapse. Mir-126 targets two distinct signaling pathways that promote cancer-mediated endothelial recruitment resulting in enhanced metastatic colonization. Our findings reveal the mechanisms by which a set of non-coding RNAs mediate metastasis suppression and reveal a novel set of miRNA targets with potential for therapeutic targeting 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 SY05-02. doi:1538-7445.AM2012-SY05-02
Abstract SY06-02: The nontraditional peptide therapeutics
Authors: Suga Hiroaki 
Published: August 2012

Abstract
Despite the fact that some peptides had strong affinity or inhibitory activity to certain proteins, because of their poor in-vivo stability there are only a limited number of drugs based on the peptide scaffold to date. However, non-standard peptides, represented by cyclosporine A that is originally isolated as a natural product and developed as an oral available immunosuppressive agent, have remarkable in-vivo stability and membrane permeability, unlike ordinary peptides. To uncover and develop more cyclosporine A-like peptide drugs, it is critical to build a non-traditional strategy involving a system that enables us to discover non-standard peptides quickly and less expensively against a wide variety of intra- and extra-cellular targets. In this talk, I shall introduce a new technology, involving genetic code reprogramming coupled with an in-vitro display, referred to as referred to as RaPID (Random non-standard Peptide Integrated Discovery) system. By means of the RaPID system, we are able to ribosomally express natural product-like peptides containing the features of macrocyclic and N-methylated backbone, and rapidly select highly active sequences against various targets. In this seminar, I shall discuss our recent advance in the discovery of macrocyclic non-standard peptides against EpCAM, Sirt2, E6AP, and JMJD2a, as examples.
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 SY06-02. doi:1538-7445.AM2012-SY06-02
Abstract SY08-01: Large-scale screens for cancer genes in the mouse
Authors: van der Weyden Louise , Rust Alistair , Perez-Mancera Pedro , Tuveson David , Jonkers Jos , Mullighan Charles , Winton Doug , Adams David 
Published: August 2012

Abstract
As efforts to sequence thousands of human cancer genomes gain momentum, the challenge of distinguishing driver cancer genes from passengers, and determining how these genes contribute to tumorigenesis remains a major challenge. Many key cancer pathways have been identified from large-scale screens in model organisms due to the fact that most cancer genes are highly conserved, and play roles in a range of critical biological processes. We have been using mouse models of bowel, breast, pancreatic cancer and leukemia, to identify novel candidate cancer genes using approaches including transposon-mediated mutagenesis coupled with high-throughput insertion site sequencing, and next-generation sequencing of mouse tumours. Using these approaches we have not only recovered known cancer genes but also a large number of new candidates, many of which appear to be disrupted in human tumours and represent potential diagnostic and therapeutic targets. I will discuss the results of the screens we have performed and give specific examples of some of the novel cancer genes discovered from this work.
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 SY08-01. doi:1538-7445.AM2012-SY08-01
Abstract SY35-01: Clonal evolution of pre-leukemic hematopoietic stem cells precedes human acute myeloid leukemia
Authors: Jan Max , Snyder Thomas , Corces-Zimmerman M. Ryan , Quake Stephen , Weissman Irving , Majeti Ravindra 
Published: August 2012

Abstract
Acute myeloid leukemia (AML) is an aggressive malignancy of hematopoietic progenitors with poor clinical outcomes. Despite the power of next-generation genome sequencing to describe AML genomes and to identify recurrent mutations, our fundamental understanding of both the genomics of leukemogenesis and the genetic heterogeneity within the precursor cells is incomplete. Founding mutations in the majority of AML cases are largely unknown because pre-leukemic cells are clinically silent and are outcompeted by their malignant descendants. Our limited knowledge of founding mutations comes from infrequent cases of AML arising secondary to antecedent clonal bone marrow disorders or rare instances of inherited syndromes, but this does not include the large majority of de novo AML cases. Recently, advances in AML stem cell biology have enabled the prospective separation of residual hematopoietic stem cells (HSC) from AML cells. We previously showed that residual HSC contain clonal antecedents of AML in patients in long-term remission post-therapy, and have proposed a model in which serial acquisition of mutations occurs in self-renewing HSC. Here, we investigated this model and the nature of founder mutations through the genomic analysis of de novo AML and patient-matched residual HSC. Using exome sequencing, we defined mutations present in individual AML genomes from cases harboring the FLT3-ITD mutation, and screened for these mutations in the residual HSC. We identified several mutations present in residual HSC retaining normal multilineage differentiation in vivo, including mutations in NPM1, TET2, and SMC1A, a newly identified recurrently mutated gene in AML. Finally, through single cell analysis, we determined that as we hypothesized, a clonal progression of multiple mutations occurs in HSC. These pre-leukemic HSC reveal the clonal evolution of AML genomes from founder mutations, suggest a potential mechanism contributing to relapse, and constitute a cellular reservoir that may need to be targeted for more durable remissions.
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 SY35-01. doi:1538-7445.AM2012-SY35-01