bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 530: MicroRNA expression profiling in MMTV-neu breast cancer mouse model
Authors: Piovan Claudia , Leva Gianpiero D. , Cheung Douglas , Fassan Matteo , Kumar Arpan , Palmieri Dario , Iorio Marilena V. , Croce Carlo M. 
Published: May 2015

Abstract
In addition to mRNA gene expression profiling, miRNA expression analyses of human breast cancers have further demonstrated another layer of the molecular diversity of this disease and may potentially be a useful diagnostic and prognostic tool for breast cancer therapy and treatment. The development and use of relevant mouse models that closely reflect genetic alterations found in human breast cancers is critical to understand malignant progression in this disease and to test developmental therapeutics. The Mammary Tumour Virus (MMTV) Long Terminal Repeat (LTR) promoter-driven HER2/neu transgenic mouse model was developed to directly assess the effects of mammary gland specific expression of the neu protooncogene.
Global miRNA expression profiling was performed on tumours derived from the MMTV-HER2/neu model. Normal mammary glands from FVB wild-type mice, HER2 overexpressing mammary glands from MMTV-HER2/neu transgenic mice and tumours derived from this model at different stages of the tumourigenic process were collected and microRNA expression profiling performed on them by Nanostring analysis. Differential expression of selected miRNAs, obtained by Nanostring screening, was further confirmed by quantitative Real Time analysis.
By analyzing global miRNA expression profile on tissues collected from MMTV-HER2/neu mice at different stages of the tumourigenesis, we identified significant differences in miRNA expression patterns between tumours and normal mammary tissue and between non-metastatic and metastatic tumours. miRNA expression characterization of tumours at various stages of development along with gene expression in mouse models would profoundly enhance our knowledge of progressive genetic changes associated with oncogene-induced events in breast cancer.
Citation Format: Claudia Piovan, Gianpiero Di Leva, Douglas Cheung, Matteo Fassan, Arpan Kumar, Dario Palmieri, Marilena V. Iorio, Carlo M. Croce. MicroRNA expression profiling in MMTV-neu breast cancer mouse model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 530. doi:10.1158/1538-7445.AM2014-530
Abstract 5303: Uptake and Efflux of 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) in human adipocytes
Authors: Yao-Borengasser Aiwei , Rogers Lora J. , Kadlubar Susan A. 
Published: May 2015

Abstract
Obesity has been linked to the development of numerous chronic diseases, including breast cancer. Although the association between obesity and breast cancer risk is clear in postmenopausal women, high body mass index (BMI) appears to protect against breast cancer in pre-menopausal women. The mechanistic basis of this “obesity paradox” is unknown. One hypothesis is that abundant adipose tissue in the mammary gland functions as a storage depot for lipid-soluble carcinogens of dietary origin, initially offering protection against exposures. Heterocyclic amines (HCAs) are pro-carcinogens that are formed from high-temperature cooked meats. Exposures to these compounds are ubiquitous in Western diets and 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP), the most mass-abundant HCA, is classified as a “probable human carcinogen.” To determine rates of influx of PhIP into adipocytes, differentiated Simpson-Golabi-Behmel Syndrome (SGBS) adipocytes were treated with 5 µM plus 0.02 µCi 14C-PhIP for 0.5, 1, 2, 5, 10, 15, 30, 45, and 60 minutes, and media was removed at time points. Cells were re-suspended in scintillation fluid, and counted with a 1450 LSL & Luminescence Count (Perkin Elmer). Influx was rapid and PhIP continued to accumulate in the cells between 15 and 60 minutes. To determine efflux, SGBS cells were exposed to 5 µM plus 0.02 µCi 14C-PhIP and allowed to equilibrate for 30 minutes. Media was removed and the cells were washed with PBS. Radioactivity retained in SGBS cells was counted at 0.5, 1, 5, 10, 30, and 60 minutes. SGBS cells retained 50% of the radioactivity for more than 10 minutes, compared to other studies where PhIP efflux from pancreatic acinii and hepatocytes occurs within the first 15 seconds. Our data demonstrates that human adipocyte efflux is significantly slower than those in other type of cells reported in the literature, suggesting that human adipocytes can sequester PhIP, thereby protecting the breast from dietary exposure to carcinogens.
Citation Format: Aiwei Yao-Borengasser, Lora J. Rogers, Susan A. Kadlubar. Uptake and Efflux of 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) in human adipocytes. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5303. doi:10.1158/1538-7445.AM2014-5303
Abstract 5304: Inhibition of kallikrein-related peptidase-4 by SPINK1
Authors: Koistinen Hannu , Domanskyy Mykola , Stenman Ulf-Håkan 
Published: May 2015

Abstract
Serine protease inhibitor Kazal type-1 (SPINK1), also known as TATI (tumor-associated trypsin inhibitor), is a 56 amino acid trypsin inhibitor, whose levels are elevated in several cancers, including those of ovaries, prostate, bladder and colon. Some mutations in SPINK1, such as N34S, are associated with pancreatitis. Furthermore, SPINK1 was recently found to be associated with ETS rearrangement-negative prostate cancers and to stimulate the invasion of prostate cancer cells, perhaps by activating the EGF-receptor. Recently, SPINK3, the mouse ortholog of SPINK1, was identified as a potent inhibitor of human kallikrein-related peptidases (KLKs) -2, -3 (PSA) and -5. We studied the effect of human SPINK1 on KLK2, -3 and -4. Synthetic cDNAs encoding wild-type and mutant forms of 56 amino acid SPINK1 without signal peptide were expressed in E. coli. The SUMOstar E. coli Expression System was used for expression and purification of recombinant SPINK1. Final purification was done using an antibody affinity column and HPLC. Enzyme activities were measured using chromogenic substrates and recombinant human KLK2 and -4, and KLK3 purified from seminal fluid. SPINK1 was found to efficiently inhibit KLK4, while KLK2-inhibition was less pronounced. KLK3 was not inhibited at all. SPINK1 mutant (K41Y), which does not inhibit trypsins, did not inhibit KLK4 either, while pancreatitis associated mutant (N34S) showed strong inhibition. It is possible that SPINK1 has a dual role in cancer, i.e., it induces tumor growth by stimulating the EGF-receptor, while by inhibiting the activity of trypsin and KLKs it suppress metastasis and activation of protease-activated receptors (PARs), which promote tumor growth.
Citation Format: Hannu Koistinen, Mykola Domanskyy, Ulf-Håkan Stenman. Inhibition of kallikrein-related peptidase-4 by SPINK1. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5304. doi:10.1158/1538-7445.AM2014-5304
Abstract 5307: Development of pIMAGO for universal detection of protein phosphorylation
Authors: Iliuk Anton , Li Li , Pan Li , Tao Weiguo A. 
Published: May 2015

Abstract
Protein phosphorylation, as the most common covalent modification of proteins, plays a critical role in the regulation of many cellular functions. Irregularities in phosphorylation network are a major cause of onset and progression of many diseases, most notably cancer. Consequently, detection of protein phosphorylation is essential in further understanding of cellular signaling pathways and mechanisms of cell growth and proliferation. To assist in effective phosphorylation analyses, we introduce here a novel technique based on soluble nanopolymers with excellent solubility, compact spherical shape and chemical homogeneity. Soluble nanopolymers functionalized with Ti(IV) ions have shown highly versatility and allow for highly efficient analyses of phosphorylation and signaling pathways.
We devise here a novel strategy, termed pIMAGO (phospho-imaging), for effective detection of phosphoproteins on a membrane in Western Blot format. Unlike antibody-based strategies, the new method is capable of selectively binding a phosphorylated residue independent of amino acid microenvironment. It shows no preference for either of the phosphosites, and thus holds great promise in biological analyses where the site of phosphorylation is not known or its specific antibody is not available. Using this technique, the phosphorylation levels of proteins of interest under physiological conditions can be readily detected as part of a standard Western Blot procedure without the need for radioactivity or expensive phosphosite-specific antibodies. The utility of the approach has been demonstrated using standard mixtures of proteins and by in vitro kinase and phosphatase assays. In addition, multiplexing capabilities of pIMAGO are presented, a feature often unavailable during antibodies-based detection. Finally, we further confirmed that the technique is sensitive and specific enough to detect endogenous phosphorylation changes by analyzing physiological signaling in number of endogenous protein complexes isolated directly from cells.
Citation Format: Anton Iliuk, Li Li, Li Pan, Weiguo A. Tao. Development of pIMAGO for universal detection of protein phosphorylation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5307. doi:10.1158/1538-7445.AM2014-5307
Abstract 5313: Phosphoproteomic analysis with reverse phase protein array identifies N-myc downstream regulated gene 1 (NDRG1) as a biomarker of phosphatidylinositol-3-kinase (PI3K)α inhibitor activity in a PTEN-deficient glioma cell line
Authors: Inoue Takeomi , Iwata Naoko , Nishiwaki Eiji , Kirii Yasuyuki 
Published: May 2015

Abstract
Aberrant activation of phosphoinositide 3-kinase (PI3K) signaling is commonly reported in cancer, and leads to deregulation of several intracellular processes, including cell survival, growth, proliferation and migration. PI3K activates AKT, serum/glucocorticoid regulated kinase (SGK), phosphoinositide -dependent kinase 1 (PDK1), mammalian target of rapamycin (mTOR), and several other molecules involved in cell progression and survival. Reports have also indicated that the deletion of the gene encoding the tumor suppressor phosphatase and tensin homologue (PTEN) is one of the key factors controlling activation of the PI3K pathway. Glioblastoma (GBM), the most common malignant brain tumor in adults, represents a compelling disease for kinase inhibitor therapy. Although many therapies to target the Ras-PI3K-mTOR axis in GBM have been attempted, their efficacies have not been pronounced, presumably because of the complexity of PI3K mediated signaling. To elucidate the role of PTEN in PI3K signaling, the phosphorylation status of two glioma cell lines, LN229 (wild type PTEN) and U-87 MG (PTEN deficient) was investigated with phosphoproteomic reverse phase protein array (RPPA). When basal phosphorylation was compared between both cell lines, the phosphorylation of N-myc downstream regulated gene 1 (NDRG1) (Thr346), a physiological substrate of SGK1, was increased in U-87 MG cells compared with levels in LN229 cells. These data suggest that PTEN deletion affects the phosphorylation status of NDRG1 in U-87 MG cells. Following treatment with PIK-90, a PI3Kα inhibitor, phosphorylation of Akt (Ser473) and its direct substrate PRAS40 (Thr246) were decreased in both cell lines, however, NDRG1 (Thr346) phosphorylation was strongly inhibited only in U-87 MG cells. These results suggest that the differential effects of PIK-90 on LN229 and U-87 MG cells is PTEN dependent, and that detecting NDRG1 (Thr346) phosphorylation could be a biomarker for PI3Kα inhibitor treatment in PTEN deleted cancer cells. Ongoing studies are focusing on elucidating the mechanism of action of PIK-90 in glioma cell lines.
Citation Format: Takeomi Inoue, Naoko Iwata, Eiji Nishiwaki, Yasuyuki Kirii. Phosphoproteomic analysis with reverse phase protein array identifies N-myc downstream regulated gene 1 (NDRG1) as a biomarker of phosphatidylinositol-3-kinase (PI3K)α inhibitor activity in a PTEN-deficient glioma cell line. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5313. doi:10.1158/1538-7445.AM2014-5313
Abstract 5319: The role of ISBER (The International Society for Biological and Environmental Repositories) in cancer research
Authors: Garcia Debra L. , Sexton Katherine , Grizzle William E. , Betsou Fay 
Published: May 2015

Abstract
High quality biospecimen collections are essential for biomarker discovery in Cancer Research. Biomarker analytical and clinical performance depends heavily upon the pre-analytical variation of biospecimens used. For this reason, standardization of procedures is of utmost importancein the collection, preparation, and storageof biospecimens, making it possible to accurately associateprocessing methods withappropriate end-use applications.
The International Society for Biological and Environmental Repositories (ISBER) is a professional society of organizations and individuals who share an interest in promoting consistent, high quality standards, ethical principles, and Best Practices in biospecimen banking. ISBER, with almost 500 individual and organizational members throughout the world, is the leading international forum for promoting innovation in the science and management of biospecimen collection, processing, storage, distribution, and use.
ISBER educational resources and meetings focus on a wide variety of topics from biorepository development, maintenance, and improvement, to technical concerns regarding equipment, quality assurance and control, regulation, human subject privacy, and confidentiality. Additional tools developed by ISBER, many of which are web-based, are available to assist researchers in ensuring biospecimen quality and biorepository compliance with Best Practices. ISBER routinely provides information about existing biorepositories and their biospecimen collections as well. For more information, please visit http://www.ISBER.org.
Citation Format: Debra L. Garcia, Katherine Sexton, William E. Grizzle, Fay Betsou. The role of ISBER (The International Society for Biological and Environmental Repositories) in cancer research. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5319. doi:10.1158/1538-7445.AM2014-5319
Abstract 5324: Pan-cancer identification of mutated pathways and protein complexes
Authors: Leiserson Mark D. , Vandin Fabio , Wu Hsin-Ta , Dobson Jason R. , Raphael Benjamin R. 
Published: May 2015

Abstract
Large-scale cancer sequencing efforts such as The Cancer Genome Atlas (TCGA) and others have shown that tumors exhibit extensive mutational heterogeneity with relatively few genes mutated at significant frequency and many genes mutated in only a small number of individuals. This long tail phenomenon complicates the identification of driver mutations by their observed frequency. The long tail is explained in part by the fact that driver mutations target genes in signaling and regulatory pathways, and these pathways may be perturbed by different mutations in different tumors.
We developed two complementary algorithms, HotNet2 and Dendrix++, to analyze combinations of mutations in known or novel pathways. HotNet2 uses prior knowledge of pathways and protein complexes represented in a genome-scale protein-protein interaction network, and identifies significantly mutated subnetworks using a heat diffusion model. HotNet2 simultaneously assesses both the significance of mutations in individual proteins and the local topology of protein interactions. Dendrix++ identifies combinations of mutations de novo, without prior knowledge of pathways or protein interactions, by finding sets of mutations that are mutually exclusive across the tumor cohort. There are numerous examples of mutually exclusive mutations between interacting proteins; e.g. BRAF and KRAS in colorectal cancer. Dendrix++ generalizes this idea to find larger groups of mutually exclusive mutations.
We applied HotNet2 and Dendrix++ to whole-exome sequencing and copy number aberration data from 3299 samples of twelve tumor types from TCGA Pan-Cancer project. Both algorithms identified gene sets that overlap well-known cancer pathways (e.g. TP53, MAPK, and RAS signaling pathways), as well as genes and complexes with less characterized roles in cancer (e.g. the cohesin and condensin complexes). HotNet2 subnetworks also contained novel candidate cancer genes that were rarely mutated in this cohort and thus not reported by single-gene tests of significance, including KDM5A, SHPRH, and ARID4A, each of which interacts with well-known cancer genes. Many of these gene sets have biological functions often perturbed in cancer, such as chromatin modification (e.g. the SWI/SNF and BAP1 complexes) and DNA damage repair (e.g. SHPRH). These results demonstrate the ability of HotNet2 and Dendrix++ to identify novel combinations of mutations in thousands of tumors, prioritizing genes and mutations in the long tail for further experimental studies.
Citation Format: Mark D. Leiserson, Fabio Vandin, Hsin-Ta Wu, Jason R. Dobson, Benjamin R. Raphael. Pan-cancer identification of mutated pathways and protein complexes. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5324. doi:10.1158/1538-7445.AM2014-5324
Abstract 5328: GIAB: Genome reference material development resources for clinical sequencing
Authors: Xiao Chunlin , Zook Justin , Trask Shane , Sherry Stephen ,   the Genome-in-a-Bottle Consortium
Published: May 2015

Abstract
Reference materials play important roles in validating performance of sequencing platforms and enabling regulations of clinical applications. Genome-in-a-Bottle (GIAB) project is a collaboration between NIST, FDA, NCBI, academic sequencing groups, sequencing technology developers, and clinical laboratories to develop analytical-grade reference genome materials and accompanying performance metrics for the development of regulations and professional standards for clinical sequencing. NCBI is serving as the Data Coordination Center (DCC) and repository for the raw sequencing reads, mapped alignments, genotypes, and other details for each sample on a dedicated FTP site (ftp://ftp-trace.ncbi.nih.gov/giab/ftp). Here we describe the processes of data generations and data submissions, and how the community can access the data. We are also developing a genome browser for data visualization. GIAB consortium plans to release data to the public on a regular basis.
Citation Format: Chunlin Xiao, Justin Zook, Shane Trask, Stephen Sherry, the Genome-in-a-Bottle Consortium. GIAB: Genome reference material development resources for clinical sequencing. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5328. doi:10.1158/1538-7445.AM2014-5328
Abstract 5333: A mathematical model for the kinetics of metastasis formation based on SEER data
Authors: El-Kareh Ardith W. , Secomb Timothy W. 
Published: May 2015

Abstract
Metastasis is responsible for most cancer mortality, yet many questions remain about how best to describe the kinetics of metastasis formation mathematically. Because the initial step of metastasis is the detachment of cells from a tumor mass, the rate of formation of new metastases is assumed to depend on the size of the original tumor mass. A power-law dependence, rather than linear proportionality, has been assumed, since access to blood vessels and lymphatics becomes more limited as tumor mass increases. Under this assumption, the cumulative distribution of fraction of patients not showing detectable metastases at diagnosis should decrease monotonically as tumor size at detection increases. Using data from the NCI's SEER (Surveillance, Epidemiology, and End Results) 1973-2010 database, it is shown here that this relation in fact shows non-monotonic behavior at larger detection sizes. A mathematical model for tumor growth and metastasis kinetics is developed to show that this implies that proliferation rates and metastatic rates are not independently distributed across the patient population, but rather, show some correlation. The model is further applied to deduce quantitative information about the size-dependence of the rate of metastasis. Kaplan-Meier curves stratified by tumor size, also computed from SEER 1973-2010 data, provide an additional data source for determining model parameters. It is found that accounting for age dependence is necessary for fitting these curves. Two possible age-related effects: a lower lethal tumor burden threshold; and an increased coefficient of metastatic rate due to declining immunity; are considered in the model, and a comparison is made of their ability to describe the observed age-dependence. In sum, the model shows how SEER data can be used to deduce information about the kinetics of metastasis formation, and is expected to have application in optimization of the treatment of metastatic tumors as well as screening schedules.
Citation Format: Ardith W. El-Kareh, Timothy W. Secomb. A mathematical model for the kinetics of metastasis formation based on SEER data. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5333. doi:10.1158/1538-7445.AM2014-5333