bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1027: Helicobacter pylori blood biomarkers for gastric cancer risk in the Shanghai Men's Health Study
Authors: Epplein Meira , Zheng Wei , Xiang Yong-Bing , Peek Richard M. , Li Honglan , Correa Pelayo , Gao Jing , Michel Angelika , Pawlita Michael , Cai Qiuyin , Shu Xiao-Ou 
Published: August 2012

Abstract
Background: Helicobacter pylori is the leading identified risk factor for distal gastric cancer, yet only a fraction of infected individuals ever develop neoplasia. To identify potential risk markers in a Chinese population where over 90% of individuals are infected with H. pylori, we assessed the association between antibodies to 15 Helicobacter pylori proteins and gastric cancer risk in a case-control study nested in a population-based cohort study. Methods: Each incident distal gastric cancer case (n = 227) identified between 2002 and 2009 among members of the Shanghai Men's Health Study was matched to two controls based on age, timing of blood collection, and recent antibiotic use. Serum levels of antibodies to 15 Helicobacter pylori proteins were assessed using multiplex serology. Multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Results: Sero-positivity to three (Omp, HP0305, HyuA) of fifteen proteins assessed were associated with an approximate two-fold significantly increased risk for gastric cancer. When excluding cases who were diagnosed within two years of study enrollment (and their matched controls), sero-positivity to two additional proteins (HpaA and NapA) showed significant associations with risk. An association with CagA sero-positivity was also suggested. Compared to individuals with ≤3 sero-positive results to the six virulent proteins identified in this population, individuals with 4-5 sero-positive results were at a two-fold increased risk (OR=1.93, 95% CI: 1.25-3.00) and individuals sero-positive to all 6 proteins had an over 3-fold increase in risk (OR=3.31, 95% CI: 1.86-5.89) for distal gastric cancer. Among individuals least likely to have begun cascade of events leading to gastric cancer, these associations were even stronger (OR=2.74, 95% CI: 1.58-4.73 and OR=4.72, 95% CI: 2.22-10.03, respectively). Conclusions: In the Chinese population, among whom H. pylori-infection is highly prevalent, increasing number of sero-positives to six H. pylori proteins (Omp, HP0305, HyuA, HpaA, CagA, and VacA) may predict the risk of gastric 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 1027. doi:1538-7445.AM2012-1027
Abstract 1033: Transcriptional factor ZBP-89 interacts with DNMT1 and HDAC3 to regulate Bak expression
Authors: Caiguo Ye , George Chen Gong , Paul Lai 
Published: August 2012

Abstract
Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide with a very high mortality. Because the success of the conventional therapies is limited, epigenetic therapy may represent an alternative for HCC management. The present study was designed to investigate whether DNA methyltransferases and histone acetylases were involved in regulation of ZBP-89-induced Bak expression. After adenovirus Ad-ZBP-89 transfection, bisulfate modificated DNA sequencing, immunofluorence staining, siRNA interference, western blotting, and enzymatic activity assays were used to analyze DNA methylation, histone modifications and the enzyme activity in human HCC cell. Based on our previous report that ZBP-89 up-regulated Bak expression, the current study revealed that ZBP-89 regulated Bak expression through interacting with HDAC3 and DNMT1. ZBP-89 could also demethylate the CpG island in Bak promoter to facilitate Bak expression and apoptosis. Additionally, ZBP-89 contributed to maintain histone H3 and H4 acetylation by inhibiting HDACs activity. ZBP-89 was found to suppress DNMT1 activity and HDAC3 activity. Conclusively, our study demonstrates a novel mechanism how the transcription factor ZBP-89 mediates epigenetic modification to promote Bak expression. The new pathway discovered may help to develop certain epigenetic therapy against HCC.
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 1033. doi:1538-7445.AM2012-1033
Abstract 1039: Histone deacetylase 8 (HDAC8) target identification and mechanism of action of HDAC8 isoform-specific inhibitors
Authors: Balasubramanian Sriram , Sirisawad Mint , Steggerda Susanne , Mani Chitra , Thiemann Patti , Buggy Joseph J. 
Published: August 2012

Abstract
HDAC8 is a member of the histone deacetylase family, but no acetylation target in cells has yet been identified. Due to a different pocket structure, most of the pan-HDAC inhibitors currently in the clinic bind poorly to it. HDAC8 knockout mice were shown to have an embryonic defect in neural crest development, but the adult mice have no other published phenotype, and its functions in adult normal or tumor cells are not well understood. In this work, we have undertaken extensive cellular and tissue localization studies, knockdown and isoform-specific inhibition studies, whole genome expression profiling, proteomics experiments to identify differentially acetylated and expressed proteins, and kinome siRNA knockdown experiments to identify pathways of activity. In total, these results point to HDAC8's essential function in many tumor cell types, not all of which are dependent upon the enzymatic activity of the enzyme.
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 1039. doi:1538-7445.AM2012-1039
Abstract 1063: The ErbB3/4 receptor ligand Heregulin negatively regulates ErbB2 and ErbB3 receptor levels
Authors: Awasthi Smita , Ghosh Arundhati , Wilson Gerald M. , Hassel Bret A. , Hamburger Anne W. 
Published: August 2012

Abstract
ErbB2 is overexpressed in 30% of breast cancers and its overexpression is associated with poor prognosis. In addition, the ErbB2/3 heterodimer forms the most potent mitogenic receptor in vitro and is key to the proliferation of breast cancer cells. Despite the importance of this heterodimer in breast cancer progression, the negative regulation of these ErbB tyrosine kinases is still poorly understood. We demonstrate here for the first time that the ErbB3/4 ligand Heregulin (HRG) reduces mRNA and protein levels of both ErbB2 and ErbB3 in human breast cancer cell lines. We have found that after 24h of HRG treatment, ErbB2 expression decreased at both the RNA and protein levels in ErbB2 overexpressing AU565, BT474 and LTLT-Ca breast cancer cell lines. In contrast, EGFR levels were unaffected by HRG treatment. An initial decline in steady state mRNA levels was first noted at 1 hour after HRG treatment. ErbB3 levels also decreased in LTLT-Ca cells after HRG treatment. Lapatinib, which inhibits ErbB2 and EGFR kinase activity and HRG induced-ErbB3 phosphorylation, diminished the HRG- induced decrease in ErbB2 and ErbB3 in AU565 and LTLT-Ca cells. This finding suggests that the kinase activity of EGFR/ErbB2 may be involved in the HRG-induced down-regulation. HRG did not change the activity of ErbB2 promoter reporter constructs spanning 215 kb to 6007 kb upstream of the ErbB2 transcription start site as indicated by luciferase assays. An ongoing study suggests that HRG could be involved in decreasing ErbB2 mRNA stability. Our findings suggest that resistance to Lapatinib may be due in part to the fact that inhibition of ErbB2/ EGFR kinase activity dampens the negative effect of HRG on ErbB2 expression, resulting in elevated levels of ErbB2 in breast cancer 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 1063. doi:1538-7445.AM2012-1063
Abstract 107: p53 mutation at codon 273 in colorectal cancer and colitis-derived ALDHhigh cells promotes sphere formation in vitro
Authors: Shenoy Anitha K. , Fisher Robert , Butterworth Elizabeth Ashley , Scott Edward , Huang Emina 
Published: August 2012

Abstract
Introduction: p53 protein is a cell cycle regulator that functions as a tumor suppressor. Mutations in the p53 gene results in uncontrolled cell division, leading to diverse types of human cancer. In the case of colorectal cancer, p53 is the last gene to be mutated in the adenoma-to-carcinoma sequence. However, in colitis, early mutations in p53 occur in the course of dysplasia-to-carcinoma transition. Analysis of these mutations in colitis and colorectal cancer can provide clues regarding the pathogenesis of colitis to cancer.Recently, we have isolated and propagated ALDHhigh colon cancer stem cells (CCSCs) from colorectal cancer patients and precursor-CCSCs (pCCSCs) from colitic patients, which may be propagated as spheres. These CCSCs and pCCSCs may be used as a model system to study the transition from colitis to cancer. To determine if any of the p53 mutations correlate with sphere formation we analyzed p53 mutations in the existing sphere isolates. Methods: We performed sequence analysis of p53 mRNA and genomic DNA on 6 ALDHhigh sphere isolates derived from human colon cancer and 2 from colitic colon. Results: 5 out of 6 (83%) colorectal cancer derived ALDHhigh sphere isolates showed mutation at 273rd codon on the 8th exon (Arg→ His), which is one of the hot spots of p53 mutations in colorectal cancer. The same mutation was also observed in the ALDHhigh sphere isolates derived from colitic patients. This mutation corresponds to the amino acid residue that is in direct contact with DNA (contact mutants), but this mutation does not result in alterations in the spatial structure of p53. However, the defect in DNA binding ability of p53 allows the cell cycle to proceed unchecked and thus this mutation correlates with sphere forming ability. Conclusions: Mutations of p53 at codon 273 on exon 8 correlates with the sphere forming ability of the ALDHhigh cells derived from human colon cancer and colitic colon. Mutational knock-in and wild-type p53 overexpression studies would be vital to further confirm the role of this mutation in sphere formation.
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 107. doi:1538-7445.AM2012-107
Abstract 1080: Effect of IGF2 overexpression on the tumorigenicity of human ovarian carcinoma cells
Authors: Brouwer-Visser Jurriaan , Cossio María J. , Chao Suzan K. , Huang Gloria S. 
Published: August 2012

Abstract
Introduction High Insulin-like Growth Factor 2 (IGF2) tumor expression correlates with reduced disease-free survival in epithelial ovarian tumors. IGF2 mRNA is also upregulated after Taxol treatment of ovarian cancer cells. The purpose of this study was to determine the effect of IGF2 overexpression on the tumorigenicity of human ovarian cancer cells. Methods HEY cells were stably transfected using lentiviral particles with IGF2 or no insert (EV) constructs. qPCR and ELISA were performed to measure the IGF2 mRNA and secreted protein expression levels, respectively. Signaling pathways were probed by immunoblotting. Tumorigenicity was evaluated in athymic nude mice by subcutaneous injection of serial cell dilutions with matrigel, followed by monitoring of in vivo tumor growth by caliper measurements. qPCR for IGF2 mRNA and immunohistochemistry for Ki67 were performed on the excised tumors. Results The IGF2 mRNA level was 4679 ±176 fold-change higher in HEY-IGF2 cells relative to HEY-EV cells (P&lt;0.0001). The amount of IGF2 protein secreted in 48 h was 5159 ng/100,000 HEY-IGF2 cells (51.6 pg/cell), and undetectable in the media of HEY-EV cells. Tyrosine phosphorylation of the IGF1-receptor was increased 13-fold in HEY-IGF2 cells. In vitro, dependency on the IGF1-receptor signaling was unaltered, as IGF2 overexpressing cells responded similarly to the IGF1-receptor inhibitor NVP-AEW541 compared to HEY-EV cells. Following an injection of one million cells with matrigel, the mean tumor volume of xenografts after 4 weeks was 1608 ±330 mm3 versus 705 ±95 mm3 for HEY-IGF2 and HEY-EV xenografts, respectively (P=0.04, N=6 per group). Immunohistochemistry for Ki67 showed a significantly higher percentage of stained nuclei in HEY-IGF2 tumors than in HEY-EV tumors (P=0.04, N=3 per group). Discussion Stable overexpression of IGF2 in HEY ovarian cancer cells resulted in an increased xenograft growth rate. Further evaluation is underway to fully characterize the mechanisms by which IGF2 overexpression promotes tumor growth.
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 1080. doi:1538-7445.AM2012-1080
Abstract 1202: A role for adhesion in epidermal growth factor receptor (EGFR)-mitochondrial translocation
Authors: Skalski Michael , Slack-Davis Jill , Parsons Sarah J. 
Published: August 2012

Abstract
Co-overexpression of the epidermal growth factor (EGF) receptor (EGFR) and c-Src often occurs in tumors, resulting in synergistic increases in oncogenic activity and correlation with poor patient prognosis in several cancers1. We have demonstrated that overexpression of EGFR and c-Src, and stimulation with EGF results in the transient translocation of both kinases to the mitochondria, which correlates with reduced adriamycin-induced apoptosis, and lowered O2 consumption and ATP production. Translocation requires EGFR endocytosis, as well as EGFR and c-Src catalytic activity2,3. It has been suggested that to translocate to the mitochondria, EGFR is retrograde trafficked to the ER, where it is removed from the membrane and then enters the mitochondria4. Here we show that EGFR remains associated with endosomal membranes upon translocation from the plasma membrane to mitochondria, as demonstrated by the colocalizaton of EGFR, mitochondria and extracellularly applied dextran. This translocation requires the activity of integrins, as cells plated on poly-L-lysine show significantly reduced mitochondrial-EGFR in response to EGF stimulation. Alternatively, adhesion to fibronectin in the absence of other extracellular signals was sufficient to activate EGFR and cause mitochondrial translocation. Adhesion resulted in phosphorylation on Y845, Y992, and Y1068, but not Y1045 of EGFR, while EGF stimulation, even on poly-L-lysine, resulted in the phosphorylation of all these sites. pY1045 is involved in Cbl recruitment and lysosomal degradation of EGFR5, suggesting adhesion stimulates EGFR signaling and mitochondrial translocation, while preventing lysosomal degradation. Future work will examine the role of Y1045 in mitochondrial EGFR translocation, mitochondrial function and resistance to chemotherapy. References: 1. Biscardi, J. S., Tice, D. A., and Parsons, S. J. (1999) Adv. Cancer Res. 76, 61-119. 2. Demory, M. L., et. al. (2009) J Biol Chem, 284: 36592-36604. 3. Boerner, J. L., Demory, M. L., Silva, C., and Parsons, S. J. (2004) Mol Cell Biol, 24: 7059-7071. 4. Cao, X., Zhu, H., Ali-Osman, F., and Lo, L.W. (2010) Mol. Cancer. 10:26. 5. Groval, L.M., Stang, E., Sorkin, A., and Madshus, I.H. (2004) Exp Cell Res, 300:388-95.
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 1202. doi:1538-7445.AM2012-1202
Abstract 1209: Detection of EGFR T790M mutation in non-small-cell lung cancer patients using colony hybridization assay
Authors: Fujita Yoshihiko , Suda Kenichi , Kimura Hideharu , Matsumoto Kazuko , Arao Tokuzo , Nagai Tomoyuki , Hayashi Hidetoshi , Furuta Kazuyuki , Kato Hiroaki , Saijo Nagahiro , Yatabe Yasushi , Mitsudomi Tetsuya , Nishio kazuto 
Published: August 2012

Abstract
Non-small-cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations (deletion in exon 19 or L858R) show a dramatic response to EGFR tyrosine kinase inhibitors (EGFR TKIs). However, most patients have a relapse within 1 year after the initiation of therapy. An EGFR secondary mutation T790M has been observed in approximately 50 % of such lung cancers that acquire resistance to EGFR TKIs. A critical question is whether the T790M mutation occurs as a result of treatment with EGFR TKIs or whether it exists prior to treatment and is selected during the course of therapy. However, its assessment can be challenging due to limited tissue availability and low sensitivity of the previously available methods. Here, we sought to detect the T790M using colony hybridization (CH) assay. This assay is able to detect mutant allele of 0.01 % in the background of wild-type allele. We assessed the T790M mutation in pretreatment specimens from 39 EGFR-TKI-treated patients with activating EGFR mutations. The T790M mutation was detected by CH in 31 of 39 patients (79 %). Median time to treatment failure (TTF) was 9 months in patients with pretreatment T790M, whereas it was 7 months in patients without the T790M mutation (P = 0.44). When we subdivided the patients with T790M into a strong and a modest positive subgroups in terms of the frequency of positive signals observed by our colony hybridization technique, seven patients with strong positivity had a TTF significantly longer than 8 patients without T790M (P = 0.0097) and 24 patients with modest positivity (P = 0.0019). Thus, the use of our highly sensitive method showed that a subgroup of patients with the EGFR mutation harbor rare T790M alleles before exposure to EGFR TKIs. However, contrary to our expectation, such patients had longer TTF.
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 1209. doi:1538-7445.AM2012-1209
Abstract 1213: EGFR interacts with fatty acid synthase
Authors: Bollu Lakshmi Reddy , Ren Jiangong , Wang Jiangong , Zhang Weihua 
Published: August 2012

Abstract
Background: Over expression of the epidermal growth factor receptor (EGFR) and fatty acid synthase (FASN) is common in cancers. It has been found that de novo fatty acid synthesis accounts for &gt;90% of total cellular lipids in cancer cells. In this study, we found that EGFR physically interacts with FASN and this interaction is independent of EGFR kinase activity. Methods: We created fourteen flag tagged domain deleted EGFR, and transfected them with FASN into HEK293T cells, and performed Co-immuno-precipitation (Co-IP) followed by Western blot analysis. Results: We found EGFR interacted with FASN independent of EGFR kinase activity. Fine scale domain mapping revealed that the transmembrane (TM) and intracellular domains of EGFR are necessary for the EGFR-FASN interaction. The extracelluar domains of L1 and LF are also required for a sufficient EGFR-FASN interaction. Conclusions: EGFR interacts with FASN independent of its tyrosine kinase activity and that the transmembrane and intracellular domain of EGFR is critical for the interaction between EGFR and FASN.
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 1213. doi:1538-7445.AM2012-1213
Abstract 1219: Defective catagen entry in EGFR deficient skin precedes cutaneous inflammation
Authors: Bichsel Kyle J. , Gaulter Jessica A. , Porto Dennis , Foote Courtney , Hansen Laura A. 
Published: August 2012

Abstract
Treatment of cancer patients with epidermal growth factor receptor (EGFR) inhibitors causes perifollicular inflammation in the skin. Mouse models with EGFR deficiency predicted this folliculitis and revealed that abrogation of EGFR disrupts hair follicle cycling. We hypothesized that the defect in progression through catagen resulting from EGFR deficiency causes cutaneous inflammation. EGFR regulation of the hair cycle and inflammation was investigated using skin-targeted deletion of Egfr (Krt14-Cre+/Egfrfl/fl mice). Hair cycle stage was assessed using histological criteria, analysis of follicular apoptosis and the position of the dermal papillae. Dorsal hair follicles of control mice synchronously entered catagen at 17 d and progressed to telogen by 21 d. In contrast, Egfr mutant follicles asynchronously entered catagen, with some follicles beginning catagen at 18 d or later, and others remaining in anagen through 24 d. Mast cells were examined because follicular mast cell precursors can facilitate the transition into catagen after their maturation and degranulation. Failed catagen progression preceded an inflammatory response in the mutant skin, which was characterized by a 40% or more increase in mast cell numbers beginning at 21 d. Mast cells in mutant skin were more likely to be degranulated as well. Neutrophils and macrophages increased in mutant skin by 28 d, subsequent to the increase in mast cell numbers. Transcriptional profiling was performed at 17 d, the time of normal catagen onset, using follicular RNA obtained from laser capture microdissection to identify EGFR-regulated mediators of the inflammatory response. In silico analyses of these data identified increased expression of 12 immune function genes in mutant hair follicles including the mast cell proteases Chymase and Tryptase. Additionally, the class I major histocompatibility (MHC) molecules H2-Q9, H2-Q7 and H2-D1 and class II MHC molecules H2-Eb1, H2-Dmb1 and H2-Dmb1/2 were over-expressed in mutant hair follicles consistent with a role for adaptive immunity in cutaneous inflammation following asynchronous catagen. Thus, an aberrant catagen transition and upregulation of pro-inflammatory genes preceded folliculitis in Egfr mutant skin.
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 1219. doi:1538-7445.AM2012-1219