bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5102: Increased plasma levels of MAPRE1, an APC interacting protein, preceding a diagnosis of colorectal cancer
Authors: Ladd Jon , Buson Tina B. , Johnson Melissa M. , Zhang Qing , Pitteri Sharon J. , Wang Hong , Prentice Ross L. , Hanash Samir 
Published: June 2012

Abstract
Longitudinal blood collections from cohort studies provide the means to search for proteins associated with disease processes prior to diagnosis. We have investigated pre-diagnostic plasma samples to determine quantitative differences in plasma protein between subjects subsequently diagnosed with colorectal cancer (CRC) and matched controls that remain cancer free during an 18 month period of active follow-up. In-depth quantitative proteomic profiling was performed on 90 pre-diagnostic plasma samples. Experiments compared nine pools each consisting of plasma aliquots from 10 CRC subjects diagnosed within 18 months after blood draw and 10 matched controls. MAPRE1 was confirmed in a set of 58 pairs of plasma from newly diagnosed CRC cases and controls using enzyme linked immunosorbent assay (ELISA). MAPRE1 was further tested by ELISA in a second independent set of 100 pre-diagnostic CRC plasma samples diagnosed within 18 months after blood draw and 100 matched controls. Proteomic analysis of pre-diagnostic plasma samples collected prior to diagnosis of CRC yielded a set of proteins with elevated concentrations (p &lt;0.05) in cases compared to control that included MAPRE1 which is a binding partner for APC. MAPRE1 and carcinoembryonic antigen (CEA) were assayed by ELISA in newly diagnosed CRC samples, yielding equally significant elevation (p &lt;0.05) among cases relative to controls for each protein with areas under the curve (AUCs) of 0.778 and 0.782, respectively. Further testing in an independent set of pre-diagnostic samples confirmed predictive value of MAPRE1 by receiver operator characteristic (ROC) achieving an AUC of 0.675 within 7 months of diagnosis. This is the first reported evidence of elevated circulating levels of MAPRE1 in colorectal cancer patient plasma. Plasma levels increased with development of CRC. Because of MAPRE1's interaction with adenomatous polyposis coli protein (APC), a known target of mutation in a majority of CRC, increased circulating levels of MAPRE1 may be an early indicator of CRC development.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5102. doi:10.1158/1538-7445.AM2011-5102
Abstract 5114: Mass spectrometric immunoassays for quantitative determination of protein biomarker variants
Authors: Nedelkov Dobrin , Trenchevska Olgica , Pupinoska Aleksandra , Phillips David , Kamcheva Elena , Romevska Slobodanka , Kiernan Urban A. 
Published: June 2012

Abstract
Post-translational modifications and genetic variations give rise to protein variants that significantly increase human proteome complexity. Modified proteins also play an important role in biological processes. Mass spectrometry, coupled to immunoaffinity separations, provides an efficient mean for simultaneous detection and quantification of protein variants. In Mass Spectrometric Immunoassays, affinity interactions are utilized to selectively retrieve specific proteins from complex biological fluids, and are followed by mass spectrometric analysis of the targeted proteins. These assays are similar to traditional enzyme immunoassays in that they use antibodies as reagents for affinity retrieval of specific proteins, but instead of enzymatic reaction for indirect protein detection, mass spectrometric analysis is used for direct identification of the proteins and their modifications.
Described here are mass spectrometric immunoassays for targeted quantitative proteomics analysis of specific protein modifications. Assays for several protein biomarkers exhibiting posttranslational modifications were developed, including beta-2-microglobulin, cystatin C, retinol binding protein, and transthyretin. The following assay performance characteristics were examined (and determined): LOQs (sufficient for quantification of normal/healthy levels of the proteins from human serum or plasma); intra- and inter-assay precision (CVs of &lt;10%), linearity and spiking recovery (90-110% range); specificity (&lt;5% cross reactivity with other proteins), and correlation with ELISA-generated results (acceptable Passing & Bablok fits and Cusum linearity p-values of &gt;0.1). The new assays were then utilized to determine the individual concentration of the specific protein variants across larger cohorts of samples (n=500), demonstrating the ability to fully quantify individual forms of post-translationally modified proteins.
The mass spectrometric immunoassays are ideally suited for detection and quantification of novel protein variants, not known a priori. These MS-based assays can find use in quantifying specific protein modifications, either as a part of a specific protein biomarker discovery/rediscovery effort to delineate the role of these variants in the onset of the disease, progression, and response to therapy, or in a more systematic study to delineate and understand human protein diversity.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5114. doi:10.1158/1538-7445.AM2011-5114
Abstract 5120: Large-scale proteome analysis reveals complex molecular abnormalities in gastric cancer
Authors: Guo Tiannan , Zhu Yi , Ng Wai Har , Kon Oi Lian , Sze Siu Kwan 
Published: June 2012

Abstract
Cancer proteomes have not been comprehensively studied on a genome-wide scale. In this work, we have catalogued the proteome of a human gastric cancer cell line, SNU5, by integrative analysis of multiple proteomic data sets generated from mitochondria, nucleus and membranes, in addition to the phosphoproteome and whole cell proteome. We report a total of 10440 proteins, of which 8578 were identified with at least two unique spectra and 7042 with more than one unique peptide. We localized gastric cancer proteins to specific organelles at higher resolution than in current knowledgebases. Proteins in sub-organelles such as the Cajal body were identified. Bioinformatic analysis suggests that the proteome map can be a tool of disease taxonomy. Seventeen oncogenesis-associated signaling pathways, including mitochondrial dysfunction, HGF signaling pathway and Eph receptor pathway, were over-represented in the gastric cancer proteome. We also documented the expression of more than 100 protein kinases in gastric cancer. Selected proteins were further investigated in primary gastric cancer tissues. Our approach demonstrates that bioinformatic integration of proteomic data sets substantially increases the depth of proteomic studies. This deep proteome map of cancer cells should aid understanding of the systems biology of gastric cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5120. doi:10.1158/1538-7445.AM2011-5120
Abstract 5127: G6-mediated inhibition of Jak2 tyrosine kinase correlates with the cleavage and cellular reorganization of vimentin
Authors: Majumder Anurima , Kirabo Annet , Karrupiah Kanchana , Tsuda Shigeharu , Caldwell-Busby Jennifer , Cardounel Arturo J. , Sayeski Peter P. 
Published: June 2012

Abstract
Hyperkinetic Jak2 tyrosine kinase signaling has been implicated in several human diseases including various leukemias, lymphomas, myelomas and the myeloproliferative neoplasms. Using structure-based virtual screening, our lab previously identified a novel Jak2 inhibitor named G6. We showed that G6 has a specific inhibitory effect on Jak2 tyrosine kinase activity and potently suppresses Jak2-mediated cellular proliferation. To elucidate the biochemical and cellular mechanisms by which G6 inhibits Jak2-mediated cell proliferation, we treated Jak2-V617F expressing human erythroleukemia (HEL) cells for 12 hours with either vehicle control (DMSO) or 25 µM of the drug and then compared their protein expression profiles using two-dimensional gel electrophoresis. One protein that was found to be differentially expressed was the intermediate filament protein vimentin. Specifically, we found that full length vimentin was robustly expressed in untreated cells and absent in G6 treated cells. We hypothesized that inhibition of Jak2-V617F dependent pathogenic cell growth by G6 correlates with the cleavage and cellular reorganization of intermediate vimentin filaments. To this end, we found that the treatment of HEL cells with G6 induced a time- and dose-dependent cleavage of vimentin. This G6-induced cleavage of vimentin was both Jak2-dependent and calpain-mediated. Using indirect immunofluorescence, we found that G6 treatment resulted in a marked reorganization of vimentin filaments within cells. Finally, using a mouse model of Jak2-V617F mediated neoplasia, we found that G6 decreased the levels of vimentin protein within the bone marrow of G6 treated mice when compared to animals that received vehicle control. Overall, these results demonstrate that G6-mediated inhibition of Jak2-dependent pathogenic cell growth correlates with the proteolytic cleavage of full length vimentin and the reorganization of intermediate vimentin filaments within cells. As such, we may have identified a biochemical and cellular mechanism whereby G6 inhibits Jak2-V617F mediated cellular proliferation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5127. doi:10.1158/1538-7445.AM2011-5127
Abstract 5128: Physical EGFR network mapping and dynamic regulation in lung cancer cells
Authors: Li Jiannong , Bennett Keiryn , Song Lanxi , Bai Yun , Yoshida Takeshi , Edwards Arthur , Kinose Fumi , Fang Bin , Zhang Guolin , Kaupe Ines , Greben Florian , Superti-Furga Giulio , Haura Eric 
Published: June 2012

Abstract
Aberrant activation of Epidermal Growth Factor Receptor (EGFR) through somatic mutations plays a critical role in the development and progression in lung cancer. A better understanding of the downstream signaling network driven by EGFR mutations could uncover novel therapeutics targets and/or resistance mechanisms. We characterized a physical EGFR network by integrating (i) protein-protein interaction data derived from tandem affinity purification (TAP) and liquid chromatography mass spectrometry (LC-MS/MS) and (ii) global phospho-tyrosine protein profile identified by immunoaffinity purification of tyrosine phosphorylated peptides coupled to LC-MS/MS. All experiments were performed in lung cancer cell lines harboring activating EGFR mutations and highly sensitive to EGFR inhibitors. We identified 266 proteins in this network including other ERBB family member (ERBB2 and ERBB3), adaptors (GRB2, SHC1, MIG6 and STS1), heat shock proteins and chaperones (HSP90 isoforms, CDC37 and BIP), proteins involved in RTK endocytosis (AP family proteins), and phosphatases (PTPN12 and PTPRA). We found ERBB3 bound EGFR but not ERBB2 while PI3K subunits are exclusively in complex with ERBB3 suggesting ERBB3 is a key linkage between EGFR and downstream PI3K/AKT signaling. CDC37, as a co-chaperone of HSP90, bound multiple kinases suggesting possible functional importance in these cells. ARHGEF5, an activator of RHO pathway signaling, was found to interact with GRB2 and SHC1. MIG6 (also known as ERRFI1 and RALT), a known negative regulator of ERB signaling, interacts with numerous components of this network, including EGFR, GRB2, STS1, SHC1, ERBB2. We found that forced expression of MIG6 in PC9 and HCC827 cells inhibits EGFR-ERK signaling. Interestingly, cells maintain AKT signaling independently of EGFR through unknown mechanism. These cells become resistance to EGFR inhibitors but are sensitized to PI3K/mTOR inhibition. STS1, a tyrosine phosphatase, can also regulate EGFR signal pathway and lead to resistance to EGFR inhibitor. Updated work will be presented. Supported by the SPORE in Lung Cancer (P50-CA119997), National Functional Genomics Center, and Austrian Proteomics Platform GZ 200.145/1-VI/1/2006, part of the GEN-AU initiative of the BM:WF.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5128. doi:10.1158/1538-7445.AM2011-5128
Abstract 5131: Escape from breast cancer therapy, are neuropilins the key
Authors: Lunj Sapna , Staton Carolyn A. , Holen Ingunn , Ballmer-Hofer Kurt , Reed Malcolm W. , Brown Nicola J. 
Published: June 2012

Abstract
The anti-VEGF antibody Bevacizumab (Bz) inhibits VEGF binding to VEGF-R1/2 and increases progression free survival in breast cancer patients. However, eventually tumors escape treatment control and we hypothesize that this may be because Bz does not prevent VEGF from binding to its alternative receptors, the neuropilins (Np1 & Np2).
Gene expression of VEGF165, VEGF165b and the VEGF receptors, VEGF-R1/2, Np1 and Np2 in human dermal microvascular endothelial cells (ECs) and three breast cancer cell lines (MCF7, MDA-MB-231 & MDA-MB-436) was assessed using standard PCR techniques and protein expression by Western blot. The effects of 4 different Np1 binding peptides and Bz were assessed on EC differentiation (Matrigel assay of tubule formation), migration (scratch assay) and proliferation (MTS assay).
PCR revealed that VEGF and Np1/Np2 are expressed in ECs and all three breast cancer cell lines whereas VEGF-R1/2 are expressed in ECs and MDA-MB-436/231 cells only. These data were also confirmed by Western blot analysis. EC differentiation when measured as tubule number or branch points was significantly inhibited (p&lt;0.005) by three Np1 binding peptides (p2, p7b & p10) whereas a fourth peptide (p1) had no effect. In contrast there was no significant effect on EC or breast cancer cell proliferation, although p10 caused a slight inhibition of MDA-MB-436 proliferation. Bz demonstrated a profound inhibition of EC tubule formation (Bz: 52.8± 7.2 vs. control: 76.3±1.4) but did not significantly inhibit EC or breast cancer proliferation. The effects of the peptides on migration was variable, with all four peptides having a slight inhibitory effect on EC migration, whereas only p1 and p7b slightly reduced MDA-MB-231 migration and only p10 reduced MDA-MB-436 migration. These data are currently being confirmed using the Boyden chamber, an alternative migration assay and combination studies of Bz with the most effective Np1 binding peptides are being performed
These data show that endothelial and breast cancer cells express Np1/Np2 receptors, and one Np1 binding peptide (p10: GSGSTRPPRRRR) inhibits both EC differentiation and breast cancer cell proliferation, and potentially EC and breast cancer cell migration in vitro, suggesting that this peptide may have therapeutic potential for breast cancer treatment. In vivo studies are evaluating the response to Np1 inhibition (p10) alone and in combination with Bz on angiogenesis in a breast tumor model using subcutaneous implantation of either MDA-MB-231 or MDA-MB-436 cells.
Supported by Breast Cancer Campaign
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5131. doi:10.1158/1538-7445.AM2011-5131
Abstract 5137: Pancreatic adenocarcinoma upregulated factor promotes angiogenesis and vascular permeability through modulation of endothelial cell activation
Authors: Kim Su Jin , Min Jeong-Ki , Lee Yangsoon , Koh Sang Seok 
Published: June 2012

Abstract
The soluble protein pancreatic adenocarcinoma upregulated factor (PAUF) is overexpressed in pancreatic cancer. We have recently reported that PAUF plays a crucial role in the progression and metastasis of pancreatic cancer cells. However its role in angiogenesis, which is crucial feature of tumor development, has not yet been understood. We here show that PAUF promotes angiogenesis and induces vascular permeability via endothelial cell activation. PAUF increased angiogenic traits of HUVEC cells such as proliferation, migration, and vascular network formation in vitro, which were abrogated by treatment with antibodies against PAUF. Consistently, PAUF stimulated the sprouting of microvessels from aortic rings ex vivo and the development of blood vessels into matrigel plug loaded with PAUF in vivo. We also found that PAUF increased permeability of endothelial cells as a result of the phosphorylation of VE-cadherin and promoted vascular leakiness of mouse skin. Intracellular signaling molecules ERK, AKT, and eNOS were activated in endothelial cell by PAUF, and chemical inhibitors for these signaling molecules inhibited PAUF-induced angiogenesis and vascular permeability. Expression analysis of several angiogenic factors indicated that these observed angiogenic effects of PAUF were independent of VEGF. We will discuss potential mechanism of angiogenesis mediated by PAUF. Collectively, our studies demonstrate PAUF as a novel angiogenic factor promoting angiogenesis and vascular permeability and suggest that targeting for PAUF can be an effective therapeutic treatment strategy to reduce tumor angiogenesis correlated with tumor progression and metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5137. doi:10.1158/1538-7445.AM2011-5137
Abstract 5150: FJX1 is an important mediator of tumor biology due, in part, to its effect ontumor vascularization
Authors: Al-Greene Nicole , Lu Pengcheng , Zi Jinghuan , Jiang Aixiang , Shyr Yu , Deane Natasha , Beauchamp R. Daniel 
Published: June 2012

Abstract
The underlying mechanisms responsible for tumor vascularization, often correlating with poor prognosis, are an important area of cancer research. We identified Four jointed box 1 (fjx1) as a candidate gene for regulating tumor vascularization in colorectal cancer (CRC) as it was inhibited in rectal cancers (n=16) after one week treatment with Celebrex. We hypothesized that FJX1 contributes to malignant cellular behavior by enhancing tumor vascularization.
Using microarray data from 255 CRC patients we determined relative fjx1 mRNA expression levels across normal, adenoma, and stages I-IV CRC. Data were validated using quantitative RT-PCR on selected patient samples. Patients were segregated as having lower or higher than median fjx1 expression and Kaplan-Meier survival estimates were derived. Biological function was tested by overexpressing Myc-tagged human FJX1 protein in various cell lines (HEK293T, YAMC, SW480) and subjecting them to invasion and proliferation assays in vitro. SW480 derivatives were also used for flank injections to assess tumorigenesis in vivo. Tumors were analyzed via immunohistochemistry for markers of proliferation, apoptosis, and endothelial cells. Finally, conditioned media from SW480 derivatives was used in vitro to test the effects on endothelial cell (HMEC-1) invasion and tube formation.
Microarray expression data from our 255 CRC patient data set showed that fjx1 mRNA is elevated in all stages of CRC as compared to normal/adenoma tissue. Higher expression of fjx1 relative to the median was associated with significantly worse overall patient survival (p=0.0125). Elevated mRNA expression from tumor samples as compared to normal was validated by qRT-PCR within a subset of patients. Over-expression of fjx1 in HEK293T, YAMC, and SW480 cells increased invasion in vitro without altering cell proliferation. Conditioned media from SW480FJX1 cells promoted endothelial tube formation and invasion in vitro as compared to conditioned media from SW480VEC. Using an angiogenesis array and ELISA we identified and confirmed that VEGF was upregulated in SW480FJX1 conditioned media as compared to SW480VEC. Finally SW480FJX1 cells were more tumorigenic than SW480VEC in vivo, in association with increased proliferation, vascularization, and decreased apoptosis.
Taken together our results support our hypothesis that FJX1 is an important mediator of tumor biology due, in part, to its effect on tumor vascularization.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5150. doi:10.1158/1538-7445.AM2011-5150
Abstract 517: Deficiency of FAK in the bone marrow compartment enhances tumour metastasis
Authors: Batista Silvia A. , Reynolds Louise , Tavora Bernardo , Hodivala-Dilke Kairbaan 
Published: June 2012

Abstract
The growth of tumours depends on the tumour microenvironment. This involves both resident stromal cells such as endothelial cells and fibroblasts and also bone marrow-derived stromal cells. Focal adhesion kinase (FAK) is a downstream effector of integrins and growth factor receptors, both known regulators of the tumour stroma. Thus FAK likely plays an important role in the regulation of the tumour microenvironment.
Here we have generated adult mice RERTnERT/ERT; FAKfl/fl (UbFAKfl/fl) where FAK is deleted ubiquitously after treatment with tamoxifen (UbFAKKO). Our data demonstrate that loss of stromal FAK inhibits tumour growth even when the tumour cells themselves still express FAK. In a parallel study we have identified that endothelial FAK is required for tumour growth and angiogenesis (Tavora et al, under review).
Moreover, we show that loss of FAK in the bone marrow compartment is sufficient to enhance tumour metastasis whilst tending to inhibit primary tumour growth. Taken together our data demonstrate that bone marrow-derived FAK plays a significant but differential role in primary tumour growth and metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 517. doi:10.1158/1538-7445.AM2011-517