bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1349: Genetic variants in DNA repair pathway genes are associated with the risk of esophageal adenocarcinoma.
Authors: Wang Yan , Ajani Jaffer A. , Ye Yuanqing , Huang Maosheng , Wu Xifeng 
Published: August 2014

Abstract
Esophageal Cancer (EC) is one of the leading causes of cancer death in the world. Over 90% of ECs are either esophageal squamous cell carcinomas (ESCC) or adenocarcinomas (EAC). EAC is the fastest growing malignancy in the US in the past three decades. In this large case/control study, we aim to assess genetic susceptibility to EAC by investigating single nucleotide polymorphisms (SNPs) in DNA repair related pathways, including nuclear excision repair (NER), base excision repair (BER) and double-strand-break repair (DSBR). The study population included 513 Caucasian EAC cases 1499 Caucasian controls. Genotyping was performed by candidate gene approach and obtained from genome-wide association study (GWAS). A total of 464 SNPs (254 SNPs in 26 NER genes, 173 SNPs in 22 BER genes and 37 SNPs in 26 DSBR genes) were included in the final analysis. Among the top significant SNPs, SNP rs10258834 in RPA3 from the NER pathway contributed to over 30% increased EAC risk (OR=1.30, 95% CI=1.12-1.51, P=5.26x10−4), SNP rs3827392 in SMC1B from the DSBR pathway was associated with a 25% increased EAC risk (OR=1.25, 95% CI=1.07-1.47, P=4.80x10−3); whereas rs3135998 in LIG3 from the BER pathway was associated with a decreased risk of EAC (OR=0.73, 95% CI=0.59-0.90, P=3.87x10−3). Unfavorable genotype analysis was performed among those SNPs showing significant association (P&lt;0.05) in individual SNP analysis. We found a strong cumulative effect overall or stratified by DNA repair sub-pathway. For example, individuals carrying 10-13 unfavorable genotypes in BER pathway exhibited a nearly four-fold increased EAC risk compared to those in the reference group with fewer than 5 unfavorable genotypes. Our results suggest that genetic variants in DNA repair pathways significantly modify EAC risk individually and jointly. The results from this study, if validated in independent populations, could potentially categorize population into different risk groups and identify high-risk individuals for cost-effective screening and early detection of this deadly disease.
Citation Format: Yan Wang, Jaffer A. Ajani, Yuanqing Ye, Maosheng Huang, Xifeng Wu. Genetic variants in DNA repair pathway genes are associated with the risk of esophageal adenocarcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1349. doi:10.1158/1538-7445.AM2013-1349
Abstract 1400: Obesity induced leptin-notch signaling axis in breast cancer.
Authors: Battle Monica , Gillespie Corey , McGlothen Tanisha , Torroella-Kouri Marta , Gonzalez-Perez Ruben R. 
Published: August 2014

Abstract
Obesity leads to increased leptin levels and signaling which has been linked to the growth of breast cancer (BC). We early identified leptin as an inducer of Notch in BC cells. However, whether leptin-induction of Notch is instrumental to the development of BC is unknown. Objective: Therefore, we examined the impact of obesity and inhibition of leptin signaling (via LPrA2 antagonist) on the growth of syngeneic E0771-derived BC and tumor expression of Notch in lean and obese mice and in E0771 cell cultures. Methods: C57BL/6J female mice were fed either high-fat diet (HFD, 60% Kcal from fat) or normal diet (10% Kcal from fat). Obesity was defined as BW ≥ 20% BW Lean-control at week 5. Lean and diet-induced-obesity (DIO) mice were orthotopically inoculated with mouse E0771 cells in the lower left region of the mammary pad. One week later the mice were treated with either (1) pegylated leptin peptide receptor antagonist 2, PEG-LPrA2 or (2) PEG-Scrambled peptide (as control; 50μl i.v. tail vein/ 0.1 mM) following the two-arm design: (a) one and (b) two doses/weekly. Treatment lasted for 4 weeks. Tumor onset and growth was determined overtime and expression of Notch, its ligands, and crosstalk factors were assessed using western blot, immunohistochemistry, and ELISA. Leptin's effects on Notch and crosstalk factors were also investigated in E0771 cell cultures. Results: Obesity induced E0771-BC onset and growth and, increased the expression of Notch in vivo. Inhibition of leptin signaling had a higher impact on DIO mice than in lean mice by delaying onset and reducing tumor growth and the expression of Notch. Therefore, high levels of leptin in DIO-mice played a positive role in tumorigenesis. Similarly, leptin induced and PEG-LPrA2 decreased Notch expression in E0771 cells in vitro. Present data further validate the idea that the consumption of a high-fat diet leads to early BC onset and growth, which was linked to the leptin-Notch axis. Our results reinforce the potential use of inhibition of leptin signaling as a novel approach to fight breast cancer, especially in obese patients showing higher levels of leptin and incidence of BC.
Funding: This work was supported by NIH/NCI 5SC1CA138658-03 and the Georgia Cancer Coalition Distinguished Cancer Scholar Award (to RRGP), NIH/2G12RR003034-26; U54 MSM/TU/UAB Cancer Center Partnership; and 1R21CA153172-01A1 (to MTK). This research was also supported, in part, facilities and support services at Morehouse School of Medicine (NIH 1C06 RR18386).
Citation Format: Monica Battle, Corey Gillespie, Tanisha McGlothen, Marta Torroella-Kouri, Ruben R. Gonzalez-Perez. Obesity induced leptin-notch signaling axis in breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1400. doi:10.1158/1538-7445.AM2013-1400
Abstract 1408: Opposing roles of p53 and autophagy in a model of PALB2-associated hereditary breast cancer.
Authors: Huo Yanying , Cai Hong , Teplova Irina R , Bowman-Colin Christian , Chen Guanghua , Pricea Sandy , Karantzaa Vassiliki , White Eileen , Xia Bing 
Published: August 2014

Abstract
Hereditary breast cancers stem from germline mutations in susceptibility genes such as BRCA1, BRCA2 and PALB2. These and the majority of other known susceptibility genes all encode products that function in the repair and response to DNA damage, particularly double strand breaks. The p53 tumor suppressor is frequently mutated in hereditary breast cancer, and results from mouse models also suggest that its inactivation is critical for tumorigenesis induced by loss of BRCA1 and BRCA2. Autophagy is an intracellular waste disposal/recycling and stress mitigation mechanism that that can impact both cancer initiation and progression, but its role in breast cancer is unclear. Here we show that, similar to Brca1 and Brca2, ablation of Palb2 in mouse mammary gland resulted in tumor development with long latency, the majority of the tumors harbored mutations in Trp53, and combined deletion of Palb2 and Trp53 led to efficient tumor formation. Interestingly, partial loss of autophagy, due to mono-allelic loss of the essential autophagy gene Becn1, delayed and reduced Palb2-associated mammary tumorigenesis in mice with Palb2 single deletion but not Palb2;Trp53 double deletion in the mammary gland. These results indicate that, in the face of DNA damage and genome alterations elicited by PALB2 loss, p53 is a barrier to cancer development whereas autophagy facilitates cell survival and tumorigenesis. Our findings also underscore the similarity between PALB2- and BRCA-associated cancers and further suggest that inhibition of autophagy may represent a new avenue to the prevention and/or treatment of hereditary breast cancers.
Citation Format: Yanying Huo, Hong Cai, Irina R Teplova, Christian Bowman-Colin, Guanghua Chen, Sandy Pricea, Vassiliki Karantzaa, Eileen White, Bing Xia. Opposing roles of p53 and autophagy in a model of PALB2-associated hereditary breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1408. doi:10.1158/1538-7445.AM2013-1408
Abstract 1440: Mechanisms of TGF-β1-induced myofibroblast/CAF differentiation in human prostate-derived mesenchymal stem cells.
Authors: Kim Woosook , Barron David , San Martin Rebeca , Ressler Steven , Rowley David 
Published: August 2014

Abstract
Reactive stroma in prostate cancer is typified by the co-evolution of myofibroblasts/CAFs. This reactive stroma is associated with most human carcinoma and is predictive of progression. TGF-β1 is a key factor in regulating reactive stroma biology. However, the origin of myofibroblasts and the mechanisms of how TGF-β1 recruits, activates and induces their differentiation are essentially unknown. We have identified mesenchymal stem cells from normal human prostate gland and evaluated their biology in a novel 3D co-culture system. Human prostate-derived mesenchymal stem cells (hpMSCs) were CD44+/CD90+, expressed other mesenchymal stem cell genes, and exhibited multipotent differentiation patterns. When co-cultured with LNCaP cells in Millicell-CM inserts or co-inoculated in nude mice, self-organizing organoids formed with a core of stromal cells and a peripheral mantel of LNCaP cells. To investigate the role of TGF-β1, the hpMSCs were co-cultured with LNCaP cells engineered to overexpress active TGF-β1. Significantly, LNCaP cells engineered to overexpress TGF-β1 induced hpMSC differentiation to prototypical reactive stroma myofibroblasts. Microarray analysis of stroma revealed 1617 gene probes with more than a 2 fold-change in the presence of TGF-β1, showing that expression of TGF-β1 in LNCaP cells drives differential gene expression in hpMSCs. Of those gene expression profiles, RUNX1 and ID1 were identified as key transcription factors in hpMSCs that mediate TGF-β1-induced myofibroblast differentiation. Knockdown of RUNX1 in hpMSCs significantly promoted differentiation to myofibroblasts. Conversely, overexpression of RUNX1 inhibited a myofibroblast gene expression signature. Together, these data implicate RUNX1 as a major regulator of the stem cell state of tissue-derived myofibroblast stem/progenitor cells and therefore a modulator of the co-evolution of reactive stroma. Furthermore, ID1 may function as a negative regulator of reactive stroma formation by promoting proliferation of transiently amplifying cells and inhibiting myofibroblast differentiation. Our data show that reactive stroma in prostate cancer initiates from activation and differentiation of CD44+/CD90+ endogenous hpMSCs through TGF-β1/RUNX1/ID1 pathway. Understanding these mechanisms is important for developing new strategies to target the microenvironment niche.
Citation Format: Woosook Kim, David Barron, Rebeca San Martin, Steven Ressler, David Rowley. Mechanisms of TGF-β1-induced myofibroblast/CAF differentiation in human prostate-derived mesenchymal stem cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1440. doi:10.1158/1538-7445.AM2013-1440
Abstract 1498: Alpha-Lipoic acid suppresses migration and invasiveness of thyroid cancer cells through inhibition of epithelial-mesenchymal transition .
Authors: Han Ji Min , Choi Hyun-Jeung , Yim Ji Hye , Kim Won Gu , Kim Tae Yong , Shong Young Kee , Kim Eui Young , Kim Won Bae 
Published: August 2014

Abstract
Reactive oxygen species (ROS) are recently known as a contributor to tumor progression and metastasis through several mechanisms including induction of epithelial-mesenchymal transition (EMT), invasion, and tumor angiogenesis. In this study, we investigated the role of alpha-Lipoic acid (ALA), a potential antioxidant, on EMT in thyroid cancer cell lines. Human thyroid cancer-derived cell lines, BCPAP (BRAF V600E), HTH83 (HRAS Q61R), CAL62 (KRAS G12R), BHT101 (BRAF V600E), and FTC133 (PTEN null) were treated with ALA, and changes in ROS generation were measured by DCFH-DA. The expression of E-cadherin, vimentin and Twist were determined by immunoblot analysis. Cell migration and invasion were evaluated by scratch assay and by Boyden chamber assay. ALA significantly decreased intracellular ROS generation in most cell lines. The total amount of E-cadherin increased and those of vimentin and Twist decreased after ALA treatment in 4 thyroid cancer cell lines (BCPAP, HTH83, BHT101 and CAL62) in a dose-dependent manner (0.2∼1.0 mM). But, the changes in E-cadherin, vimentin and Twist were opposite in FTC133 cells. The cell migration and invasion ability decreased after treatment with ALA in all cell lines except FTC133 (PTEN null cell). These results suggest that ALA is a potential agent to inhibit EMT resulting in suppression of migration and of invasiveness in thyroid cancer cell lines with RAS or BRAF mutation, probably through reducing cellular amount of Twist. We suggest that it might be caused by antioxidant effects of ALA, but the exact mechanism of action of ALA is not clear yet. ALA could be a novel, potential agent to suppress metastasis of tumors in patients with thyroid cancer.
Citation Format: Ji Min Han, Hyun-Jeung Choi, Ji Hye Yim, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Eui Young Kim, Won Bae Kim. Alpha-Lipoic acid suppresses migration and invasiveness of thyroid cancer cells through inhibition of epithelial-mesenchymal transition . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1498. doi:10.1158/1538-7445.AM2013-1498
Abstract 1499: Role of Twist for maintenance of EMT in colon cancer cell .
Authors: Kim Hye Ryeon , Kim SoYoung , Baik Young Ae , Hong Hye Kyung , Lee Woo Yong , Cho Yong Beom 
Published: August 2014

Abstract
Epithelial-mesenchymal transition or transformation (EMT) is a process characterized by loss of cell adhesion, repression of E-cadherin expression, and increased cell motility. Epithelial-mesenchymal transition (EMT) confers tumor cells with metastatic dissemination, cancer stem cell-like characters and drug resistance. However, the molecular mechanism for metastatic dissemination remains unclear. Initiation of metastasis involves invasion, which has many phenotypic similarities to EMT, including a loss of cell-cell adhesion mediated by E-cadherin repression and an increase in cell mobility. In this study, we induced EMT in colon cancer cell line LoVo with expression of Twist, a key transcriptional factor of EMT. The metastasis associated with EMT was determined E-cadherin, vimentin and β-catenin protein expression by western blot and morphological changes associated with EMT in these cells. We found that expression of Twist induced a morphological change associated with EMT in these cells. We also found that the E-cadherin was significantly decreased in Twist-overexpressing cells LoVo. Interestingly, we showed that β-catenin was activated in these Twist-overexpressing cells. Our results indicate that activation of β-catenin is required for the sustention of EMT-associated metastasis dissemination.
Citation Format: Hye Ryeon Kim, SoYoung Kim, Young Ae Baik, Hye Kyung Hong, Woo Yong Lee, Yong Beom Cho. Role of Twist for maintenance of EMT in colon cancer cell . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1499. doi:10.1158/1538-7445.AM2013-1499
Abstract 1508: Gene expression analysis of perfusable nodules grown on ex vivo 3D model shows effects on extracellular matrix, cell signaling and immune response.
Authors: Mishra Dhruva K. , Creighton Chad , Zhang Yiqun , Gibbons Don L. , Kurie Jonathan M. , Kim Min P. 
Published: August 2014

Abstract
Tumor microenvironment plays a very important role in regulating the cell behavior within a tissue, largely by interacting with the extracellular matrix (ECM). Recently, our lab has developed a novel ex vivo lung model that forms perfusable tumor nodules, which mimic human lung cancer histopathology and protease secretion patterns better than tumor cells grown on a petri dish. In this study, we have compared the genome-wide gene expression profiles (Affymetrix 430_2) and protein arrays (Reverse phase protein array or RPPA) of 2D (monolayer) culture versus our ex vivo 3D cell culture using 393p cells, derived from mice lung cancer. Expression array data showed a set 1314 gene probes differentially expressed between monolayer 2D culture and 3D ex vivo cell culture. Gene Ontology (GO) analysis of differentially expressed genes showed the upregulation of several genes associated with extracellular matrix (ECM1, BMP15, FMOD, cathepsin, MMP9, MMP10), cell signaling (VEGFA, TGFB2, FGF20), and immune response (C1, C3, MHC class II, IL1α, IL1RA, IL13, TNF receptor superfamily, CXCL2). Selected genes were also validated using real time PCR. We found 46 proteins with significant (p&lt;0.01) differential levels in 2D vs 3D cell cultures of 393p. The proteins associated with extracellular matrix (Collagen VI, Caveolin1, Fibronectin) and cell signaling (mTOR, p38 (phosphorylated), Caspase 7 (Cleaved), BAD (phosphorylated), PI3K) were upregulated in 3D ex vivo cell culture compared to conventional 2D culture. Thus, our results showed the insightful influence of the 3D ex vivo model and its three-dimensional perfusable environment over cell growth and its behavior in terms of significant differences in gene expression and protein patterns as compared to the same cells grown on conventional 2D cell cultures.
Citation Format: Dhruva K. Mishra, Chad Creighton, Yiqun Zhang, Don L. Gibbons, Jonathan M. Kurie, Min P. Kim. Gene expression analysis of perfusable nodules grown on ex vivo 3D model shows effects on extracellular matrix, cell signaling and immune response. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1508. doi:10.1158/1538-7445.AM2013-1508
Abstract 1521: Role of the guanylate-binding-protein 1 (GBP-1) in immunoediting of colorectal carcinoma.
Authors: Britzen-Laurent Nathalie , Lipnik Karoline , Ocker Matthias , Naschberger Elisabeth , Schellerer Vera , Croner Roland , Vieth Michael , Waldner Maximilian , Steinberg Pablo , Hohenadl Christine , Stürzl Michael 
Published: August 2014

Abstract
The human guanylate-binding protein 1 (GBP-1) is among the proteins the most highly induced by IFN-γ in every cell type investigated as yet. In vivo, GBP-1 expression is associated with the presence of inflammation and has been observed in autoimmune diseases, inflammatory bowel diseases (IBD) and cancer. In colorectal carcinoma (CRC), we previously reported that the expression of GBP-1 in the cells of the desmoplastic stroma correlates with the presence of an IFN-γ-dominated Th1 microenvironment and with an increased cancer-related 5-year survival. Moreover, GBP-1 expression in the blood vessels of CRC tissue was associated with a reduced angiogenesis. However, the expression and the role of GBP-1 in the tumor cells of CRC remained unknown.
In the present study, the analysis of GBP-1 expression in a series of 185 CRCs by immunohistochemistry confirmed that GBP-1 is expressed in stroma cells of CRCs and revealed a significantly less frequent expression in tumor cells, which was contradictory with the broad inducibility of GBP-1. Furthermore, three of six CRC cell lines treated with IFN-γ were unable to express GBP-1 indicating a reduced inducibility in colorectal tumor cells. On the contrary, non-transformed colon epithelial cells strongly expressed GBP-1 in vitro in presence of IFN-γ and in vivo in IBD. Reconstitution of GBP-1 expression in a negative CRC cell line inhibited cell proliferation, migration, invasion and anchorage-independent growth. Using RNA interference, we showed that GBP-1 mediates the anti-proliferative, anti-migratory, anti-invasive and anti-clonogenic effects of IFN-γ in CRC cells. In addition, GBP-1 was able to inhibit tumor growth in vivo. Altogether these results suggested that GBP-1 acts directly as a tumor suppressor in CRC by mediating the effects of IFN-γ. In addition, the loss of GBP-1 expression in tumor cells indicated that tumor evasion from the IFN-γ-dominated Th1 immune response might have occured. This was confirmed by showing, first, that the absence of GBP-1 inducibility in CRC cell lines correlates with resistance to the anti-proliferative and pro-apoptotic effects of IFN-γ and, second, that the resistant cell lines exhibit defects in the IFN-γ signaling pathway.
Citation Format: Nathalie Britzen-Laurent, Karoline Lipnik, Matthias Ocker, Elisabeth Naschberger, Vera Schellerer, Roland Croner, Michael Vieth, Maximilian Waldner, Pablo Steinberg, Christine Hohenadl, Michael Stürzl. Role of the guanylate-binding-protein 1 (GBP-1) in immunoediting of colorectal carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1521. doi:10.1158/1538-7445.AM2013-1521
Abstract 1523: MALDI mass spectrometry imaging for on-tissue spatial profiling of tumor-specific N-linked glycans and lipids in renal carcinomas.
Authors: Drake Richard R. , Powers Thomas , Jones Ellen , Lance Raymond S. , Mehta Anand S. , Troyer Dean A. 
Published: August 2014

Abstract
Pathologic staging of renal clear cell carcinoma (ccRCC) provides useful but limited prognostic information suggesting that there are underlying molecular processes not readily identified through conventional histopathological techniques in the primary tumor. At the molecular level, transcript, metabolomic and protein expression patterns have indicated a striking Warburg Effect profile in ccRCC tissues, with major affects on sugar and lipid metabolism. Our group has been applying MALDI-MS imaging approaches to ccRCC tissues to profile lipids and glycans associated with disease progression. As both lipids and glycans can act as signaling molecules and have been associated with cancer progression, ccRCC tissues were selected by a pathologist to contain substantial tumor, non-tumor and tumor margin regions to characterize the differential localization of lipid and glycan species within the tissue. Lipid profiles from fresh-frozen tissue slides coated in DHB matrix were obtained on a dual source Bruker Solarix 70 FTICR mass spectrometer. Glycans were imaged in a similar fashion with a method developed by our lab using protein N-glycanase F to release protein bound N-glycans. There are clear patterns of specific lipid and glycan species that are only present along the margin of the tumor and non-tumor interface, or those primarily localized in non-tumor or tumor regions. Off-tissue extraction of lipids and glycans from similarly processed tissues and further mass spectrometry analysis was done to confirm structural designations. Linkage of differentially expressed lipid and glycan species with clinical data and other molecular markers of ccRCC is ongoing. This approach has the potential to not only improve prognostic assessment and enhance post-operative surveillance, but also to better define the underlying biology of ccRCC aggressiveness and identify new rational targets for therapeutic intervention.
Citation Format: Richard R. Drake, Thomas Powers, Ellen Jones, Raymond S. Lance, Anand S. Mehta, Dean A. Troyer. MALDI mass spectrometry imaging for on-tissue spatial profiling of tumor-specific N-linked glycans and lipids in renal carcinomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1523. doi:10.1158/1538-7445.AM2013-1523