bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 32: P190B RhoGAP overexpression drives mammary epithelial cell proliferation by altering stromal-epithelial interactions in the developing mammary gland
Authors: Gillette Melissa , McHenry Peter , Blumenthaler Alisa , Chang Peggy , Vargo-Gogola Tracy 
Published: August 2012

Abstract
Breast cancer development and progression is enabled by alterations in the surrounding stroma originating from stromal interactions with cancerous epithelium. Rho GTPases and their regulators have been implicated as important mediators of stromal-epithelial interactions in mammary epithelial cells (MECs), and alterations in the microenvironment profoundly affect MEC morphogenesis in a Rho GTPase-dependent manner. Previously, we demonstrated that p190B Rho GTPase activating protein (RhoGAP), a major inhibitor of Rho GTPases, has pro-tumorigenic functions during MMTV-Neu induced mammary tumorigenesis. We hypothesized that p190B overexpression in the epithelium promotes mammary tumor development by altering stromal-epithelial interactions to drive MEC proliferation and disrupt tissue architecture. To investigate this hypothesis, we examined the effects of p190B overexpression in the developing mammary gland (MG) using Tet-regulatable p190B overexpressing mice. Interestingly, overexpression of p190B in the mammary epithelium during postnatal MG development causes hyperbranching and disorganization of the ductal tree. Using a combination of in vivo morphometric and immunohistochemical analyses and in vitro stromal-epithelial co-cultures, we have demonstrated that p190B overexpression in MECs activates fibroblasts in the adjacent microenvironment leading to increased extracellular matrix (ECM) deposition, elevated expression of the collagen crosslinking enzyme lysyl oxidase, and increased expression of potent regulators of branching morphogenesis, including FGF and TGFβ growth factors. These stromal alterations correlated with increased proliferation of p190B overexpressing MECs in vivo. Taken together, these data suggest that p190B overexpression may contribute to mammary tumorigenesis by creating a pro-tumorigenic stromal environment leading to increased MEC proliferation and altered tissue architecture.
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 32. doi:1538-7445.AM2012-32
Abstract 320: Investigating the patterns of nuclear factor-kappa B activity in the host-tumor microenvironment during ovarian cancer progression
Authors: Wilson Andrew J. , Lee Hye-Jeong , Barham Whitney , Chen Lianyi , Onishko Halina , Khabele Dineo , Yull Fiona 
Published: August 2012

Abstract
Most women diagnosed with ovarian cancer initially present with metastatic disease characterized by peritoneal implants and ascites. Activation of inflammatory processes mediated by nuclear factor-kappa B (NF-κB) is thought to be critical to the distinct clinical pattern of spread of ovarian tumors. However, the relative contribution of NF-κB activity in tumor cells and host inflammatory cells to ovarian cancer progression remains unknown. Therefore, our goal was to develop and characterize model systems to investigate NF-κB activity in these cell populations during ovarian tumorigenesis. To study the host NF-κB response, ID8 mouse ovarian cancer cells were injected intra-peritoneally into C57BL/6 mice carrying an NF-κB-dependent green fluorescent protein (GFP)/luciferase fusion transgene (NGL). In a reciprocal approach, ID8 cells stably expressing the NGL reporter (ID8-NGL) were injected into wild-type C57BL/6 mice to investigate NF-κB activation in the developing tumor. Non-invasive imaging of the mice was performed by bioluminescence imaging (BLI) of the NGL reporter and by positron emission tomography (PET-CT) imaging of abdominal tumor burden. Preliminary experiments confirmed these models were highly reproducible, with peritoneal-wide tumor dissemination accompanied by the onset of late-stage, irreversible ascites. Mice injected with ID8-NGL cells showed greater than 100-fold increase in NF-κB reporter activity during tumor progression. There was a modest overall decrease in abdominal NF-κB activity over time in ID8-injected NGL mice, although the possibility of “masking” effects of the ascites fluid on bioluminescence, and NF-κB activity in specific host cell populations, need to be elaborated. These models will allow us to define the patterns of NF-κB activity in the host-tumor microenvironment during ovarian cancer progression, and will provide a powerful platform for future preclinical investigation of novel therapeutic agents targeting NF-κB in ovarian 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 320. doi:1538-7445.AM2012-320
Abstract 3202: Universal detection of protein phosphorylation based on multi-functionalized soluble nanopolymers
Authors: Iliuk Anton , Pan Li , Liu Shawn , Martinez Juan , Hall Mark , Liu Xiaoqi , Tao Andy 
Published: August 2012

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 (Western Blot format) or in a 96-well plate (ELISA 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 or ELISA procedures without the need for radioactivity or expensive phosphosite-specific antibodies. The utility of the approach has been demonstrated using standard mixtures of proteins, by in vitro kinase and phosphatase assays, as well as with kinase inhibitor screening and enzyme profiling. 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: {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 3202. doi:1538-7445.AM2012-3202
Abstract 3204: Novel, rapid and sensitive technology to analyze gene expression directly from archived FFPE clinical oncology specimens without sample preparation
Authors: Kim Chang Hee , Gerstner Arpad , Abedi Majid R. , Childers John R. , Terbrueggen Robert 
Published: August 2012

Abstract
Formalin-Fixed Paraffin Embedded (FFPE) tissue samples are the standard for clinical oncology tissue sample archiving worldwide. It is estimated that there are approximately a billion FFPE tissue cancer samples archived in hospitals and tissue banks around the world, and many of these samples have full clinical annotation including long term follow-up data. Current methods of analyzing gene expression in these samples involve laborious and expensive sample preparation protocols and long turnaround times (2 days or longer). We have developed a novel, rapid (3 hours), sample-to-answer technology to analyze gene expression from clinical FFPE tissues without the need for RNA extraction. The technique is highly sensitive and requires only 2 mm x 5 mm x 10 microns of FFPE material scraped from a pathology slide. The gene expression data obtained directly from FFPE without sample preparation correlates highly with data obtained on RNA extracted from the same FFPE sample using conventional methods. Importantly, the gene expression data obtained from prostate and breast FFPE samples correlate highly with microarray data, and with data from matching mirrored FF (Fresh Frozen) samples. The assay can be developed for detection using Luminex instrument or Capillary Electrophoresis instrument (Caliper GX or ABI 3500).
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 3204. doi:1538-7445.AM2012-3204
Abstract 3205: Isolating RNA, DNA and protein from the same sample allows correlation of multiple biomarkers
Authors: Fekete Richard A. , Karberg Mike , Cheng Angie , Chapman Laura , Gonzalez Marie 
Published: August 2012

Abstract
DNA, RNA or proteins are routinely analyzed as markers to define the type and state of tumorigenicity. Each of these analytes provide a unique set of information in order to detect differences such as chromosomal mutations, imbalances in gene expression, and changes in protein signaling networks. Limited samples, such as biopsies and small tumors, are a common sample type, however, due to their small size the analysis of more than one of these analytes from the same sample can be challenging. Taking more than one sample (biopsy), or splitting a sample in order to isolate one of these anlaytes from each section raises questions regarding sample heterogeneity. This is particularly important where one section of a tumor may be different from another, and can even provide misleading information regarding the correlation of DNA, RNA or protein markers. Another issue raised with splitting samples is that two of the analytes are lost when the third is isolated. This can lead to the loss of important information, and the low yield can limit the number and methods used for analysis. Being able to analyze DNA, RNA and proteins from the same sample is particularly crucial during biomarker discovery and correlation. Here we describe a new, quick and easy to use method to isolate DNA, RNA and proteins from small sized tumor and normal adjacent tissue and demonstrate that not only is the entire sample maintained giving us more sample for analysis (no analyte is lost when isolating the other), but there is no concern regarding heterogeneity. Using these samples we demonstrate the correlation of DNA, mRNA, miRNA and protein using Next Generation Sequencing, qPCR, Western and ELISA and associate these with tumorigenicity.
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 3205. doi:1538-7445.AM2012-3205
Abstract 3255: IKBKE is induced by STAT3 and tobacco carcinogen and determines chemosensitivity in non-small cell lung cancer
Authors: Guo Jianping , Kim Donghwa , Kurtyka Courtney , Chen Huihua , Wu Danwei , Mittal Aman , Cheng Jin Q. 
Published: August 2012

Abstract
Serine/threonine kinase IKBKE is a newly identified oncogene, however, its regulation remains elusive. Here, we provide evidence that IKBKE is a downstream target of STAT3 and that tobacco induces IKBKE expression through STAT3. Ectopic expression of constitutively active STAT3 led to increase of IKBKE mRNA and protein levels, whereas inhibition of STAT3 reduced IKBKE expression. Further, ex-pression levels of IKBKE are significantly associated with STAT3 activation and tobacco use history in NSCLC patients examined. In addition, we show induction IKBKE by two components of cigarette smoke, nicotine and the NNK. Upon exposure of nicotine or NNK, cells express high levels of IKBKE protein and mRNA, which are largely abrogated by inhibition of STAT3. Characterization of the IKBKE promoter revealed 2 STAT3 response elements that directly bind to STAT3 and respond to nicotine and NNK stimulation. Notably, knockdown of IKBKE not only selectively sensitizes NSCLC cells to chemotherapy but also abrogates the protective effects of constitutively activate STAT3 and nicotine on gemcitabine and cisplatin-induced apoptosis. These data indicate for first time that IKBKE is a direct target of the STAT3 and is induced by tobacco carcinogen through STAT3 pathway. In addition, our study also suggests that IKBKE is an important therapeutic target and could play a pivotal role in tobacco-associated lung carcinogenesis.
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 3255. doi:1538-7445.AM2012-3255
Abstract 3257: Nodal signalling in choriocarcinoma cells
Authors: Law Jeffrey , Luca Alice , Zhang Guihua , Postovit Lynne-Marie , Bhattacharya Moshmi 
Published: August 2012

Abstract
Choriocarcinoma is an aggressive cancer that arises when the invasion of placental trophoblast cells into the endometrium becomes dysregulated. Trophoblast invasion is a complex phenomenon, dependent on cues that drive trophoblast invasion, as well as factors to ensure that placental invasion does not extend beyond the myometrium. Nodal, a member of the TGF-β superfamily, is expressed throughout the endometrium during the peri-implantation period and in invasive trophoblast cells. However, Nodal's exact role in placental function is unclear. Nodal signals by activating the ALK4/7, ActRIIB and Cripto-1 receptor complex and emerging evidence suggests that its signalling strength can be controlled at the level of receptor endocytosis into signaling endosomes. Two key regulators of receptor endocytosis and cell invasion are the α-arrestins, multifunctional scaffolding proteins and Ral GTPases, members of the Ras superfamily. Ral can bind to ActRIIB, and its activity can be regulated by Ras, as well as by α-arrestins, in a Ras-independent manner. We thus hypothesized that Nodal promotes trophoblast invasion via a α-arrestin/Ral-mediated pathway. The specific objectives of my study are to (i) determine the effects of Nodal on trophoblast invasion, (ii) elucidate a role for α-arrestin / Ral signaling in regulating Nodal-induced trophoblast invasion. We found that Nodal stimulates the invasion of both the non-malignant HTR-8SV/neo trophoblast and JAR choriocarcinoma cells using Matrigel-coated transwell chamber assays. Interestingly, we found that the JAR choriocarcinoma cells responded differently to Nodal in that while HTR-8SV/neo invasion returned to baseline levels, JAR choricocarcinoma cells continued to invade even at the higher concentrations of Nodal (100ng/mL & 500ng/mL). For this reason, we decided to look at potential differences in the regulation of Nodal-induced invasion between the non-malignant HTR-8SV/neo trophoblast and JAR choricoarcinoma cell lines. We found that the JAR choriocarcinoma cells differentially expressed Ral and α-arrestin proteins compared to the HTR-8SV/neo cells. Additonally, endogenous Ral and α-arrestins associate with the ALK4 and 7 receptors, and knockdown of these molecules impaired Nodal-induced invasion. Thus, our data reveal a novel function for Nodal in modulating trophoblast invasion via a α-arrestin/Ral signaling pathway.
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 3257. doi:1538-7445.AM2012-3257
Abstract 3258: Targeted-deletion of Ptp4a3 suppresses murine colon tumorigenesis
Authors: Zimmerman Mark W. , Homanics Gregg E. , Lazo John S. 
Published: August 2012

Abstract
Protein tyrosine phosphatase 4a3 (Ptp4a3, PRL-3) is a small, prenylated, 4a-family phosphatase that is highly conserved throughout mammalian species. Elevated expression levels commonly seen in human cancers, particularly metastatic colorectal cancer, suggest that Ptp4a3 may serve as a target for novel anticancer therapeutics. Ectopic overexpression of Ptp4a3 in cell culture models often enhances the cellular properties of migration and invasion. While Ptp4a3 has historically been associated with late-stage disease and metastatic progression, we observed increases in Ptp4a3 mRNA in the colon immediately following treatment with the colon pro-carcinogen azoxymethane (AOM). In the AOM colon cancer model, wildtype C57BL/6 mice develop approximately 7-10 tumors per mouse in the distal colon. The resulting tumors exhibit an average of 4-fold upregulation of Ptp4a3 mRNA relative to normal colon epithelium, as well as positive immunohistochemical staining indicating the presence of PTP4A3 protein. To further understand this promising target, we have created the first Ptp4a3 knockout mouse model. Ptp4a3 knockout mice are viable and appear normal, although male mice appear to have a slightly reduce body mass index. Interestingly, Ptp4a3 knockout mice developed fewer colon tumors than wildtype mice with the AOM model, suggesting that Ptp4a3 may have a role in colon tumorigenesis and the cellular response to genotoxic stress.
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 3258. doi:1538-7445.AM2012-3258
Abstract 3259: TGFβ signaling is frequently attenuated in hepatocellular carcinomas but is retained for malignant phenotypes in some hepatocellular carcinoma cells
Authors: Mu Xiaoxin , Herzig Maryanne C. , Washburn William K. , Walter Christi A. , Halff Glenn A. , Sun Lu-Zhe 
Published: August 2012

Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. Its development and progression have been shown to be regulated by various cytokines including TGFβ. However, the role of TGFβ signaling in the progression of HCC remains controversial. In the current study, we examined the expression levels of TGFβ pathway components and the activation status of Smad2/3 proteins as reflected by phospho-Smad2/3 levels in human and mouse HCC tissues and human HCC cell lines. We also investigated whether abrogation of TGFβ signaling in HCC cell lines that are responsive to TGFβ affects the growth and metastasis of transplanted HCC cells in nude mice. Quantitative real-time RT-PCR and Western immune blotting analyses reveal widespread down-regulation of TGFβ signaling pathway components including Smad2/3 and TGFβ type I and II receptors in HCC tissues of patients and mice in comparison to adjacent normal tissues. Treatment of our HCC cell lines (SNU398, SNU423, HepG2, and Sk-Hep-1) with TGFβ1 revealed that the SNU398 cell line was refractory whereas the other three cell lines were sensitive to TGFβ as determined with a number of in vitro assays including Smad phosphorylation, gene transcription, and growth inhibition assays. Knockdown of TGFβ type II receptor with shRNA significantly reduced TGFβ signaling activity in the Sk-Hep-1 cell line resulting in suppressed growth of its subcutaneous tumors and reduced metastasis potential when the cells were inoculated through tail vein injection. Our results suggest that TGFβ signaling may play a suppressive role in early stage of HCC development, but a promoting role in advanced stage, which is represented by the Sk-Hep-1 cell model.
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 3259. doi:1538-7445.AM2012-3259
Abstract 3260: Primary cilia are lost early in prostate cancer progression
Authors: Hassounah Nadia , McDermott Kimberly , Nagle Raymond 
Published: August 2012

Abstract
Prostate cancer is the most prominently diagnosed cancer in men, aside from non-melanoma skin cancer, and the second leading cause of cancer related deaths in men in the U.S. Little is known about the role of primary cilia in prostate cancer progression, so our goal is to elucidate this role. Primary cilia are microtubule-based organelles present on many mammalian cell types and help the cell sense the extracellular environment. Various signaling pathways important in development involve primary cilia, such as the Hedgehog (Hh) and Wingless/Int (Wnt) pathways, and these pathways are known to be misregulated in prostate cancer. Dysfunction of primary cilia is the cause of numerous ciliopathies, such as polycystic kidney disease and Bardet-Biedl syndrome, and has been linked to cancers, like basal cell carcinoma and medulloblastoma. We hypothesize that primary cilia suppress prostate tumorigenesis, and cilia loss promotes prostate cancer by altering cell signaling pathways like Hh and canonical Wnt. To test this hypothesis, we looked in human prostate cancers at cilia, Hh and canonical Wnt signaling. Human prostate tissue from prostate cancer patients was stained for ciliary proteins (acetylated and gamma tubulin). The expressions of these proteins were analyzed using confocal microscopy and compared between adjacent normal, hyperplastic, prostatic intraepithelial neoplasia (PIN), malignant and perineural invasion areas of each patient's tissue. As a control, normal prostate tissue from bladder cancer patients who underwent prostatectomies as part of treatment was used. A marked decrease in the percentage of ciliated cells in cancer and PIN was observed compared to normal prostate tissue. Higher grade cancer (Gleason sum α7) also had fewer cilia than lower grade (Gleason sum = 6). We are currently investigating Hh and canonical Wnt signaling activity in serial sections of the tissue used to analyze primary cilia. The expressions of Beta-Catenin, a protein used to measure canonical Wnt signaling activity, and Gli1, a transcription factor used as a readout of Hh activity, are being analyzed based on expression levels and localization within the cell, and correlated to primary cilia data. Thus far, our results suggest a role of primary cilia in promoting prostate cancer 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 3260. doi:1538-7445.AM2012-3260