bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3806: Stimulation of anti-leukemia immune response by a rice protein prolamin
Authors: Liao Hui-Fen , Chen Yu-Jen , Chen Yu-Yawn 
Published: February 2011

Abstract
Rice (Oryza sativa), an important cereal as a staple food worldwide, has been demonstrated that its water extracts benefit anti-leukaemia immunity. The present study isolated and characterized the active rice proteins and assessed the anti-leukemia response via in vitro and ex vivo experiments. Proteomic analysis identified various protein spots known with functions involving metabolism-related, transport, storage, antioxidation, development, and disease resistance proteins. Among these, storage proteins were the most abundant. To avoid masking the other relatively scanty rice storage proteins, albumin, globulin, glutelin and prolamin were separated and quantified. Prolamin-prepared conditioned medium of human mononuclear cells (MNC-CM) showed the greatest inhibition of human leukaemia U937 cell growth. Prolamin enhanced MNC to secrete tumor necrosis factor-α and prolamin-prepared MNC-CM induced U937 cells toward monocyte differentiation, not only by morphological observation, but also by NBT-reduction test. Neutralization of prolamin by polyclonal antibody attenuated its activity. Prolamin has greater activity than wheat gluten (glutenin and gliadin), which can cause celiac disease (CD). Additionally, rice proteins were undetectable by wheat gliadin-specific antibody, suggesting that rice may be an ideal candidate of food substitute in CD patients. In conclusion, rice prolamin is effective in activating human anti-leukaemia immunity and may not induce unwanted inflammatory diseases.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3806.
Abstract 383: Down-regulation of tumoral Hypoxia-Inducible Factor-1α expression in OVCAR-3 tumors by albendazole
Authors: Pourgholami Mohammad H. , Cai Zhao Yan , Badar Samina , Poruchynsky Marianne , Morris David Lawson 
Published: February 2011

Abstract
Purpose: To determine if albendazole (ABZ) interferes with the tumoral production of HIF-1α and VEGF proteins.
Procedures: Human ovarian cancer OVCAR-3 cells were exposed to hypoxic conditions and the affect of ABZ on HIF-1α and VEGF expression was determined. In vivo, female nude mice bearing intraperitoneal tumors were treated with an acute dose of ABZ (150 mg/kg, i.p.), and then euthanased at various time points (1, 6, 24, 48 and 72 h). Excised tumors were analysed for HIF-1α and VEGF expression.
Results: ABZ blocked the hypoxia-induced surge in HIF-1α protein. In mice, tumoral expression of HIF-1α and VEGF proteins were highly suppressed by ABZ in a reversible time-dependent manner. In drug treated mice, tumor VEGFmRNA levels were also profoundly suppressed.
Conclusion: The results show that the anti-VEGF effect is mediated through the inhibition of HIF-1α.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 383.
Abstract 3871: Per1 is phosphorylated by ATM/ATR and is involved in the G2/M checkpoint response
Authors: Gery Sigal , Tabasyhi Takayuki , Nowak Verena , Alvarez Rocio , Sohn Julia , Koeffler Phillip H. 
Published: February 2011

Abstract
Circadian clocks are found in most organisms and influence a large array of cellular, physiological and behavioral processes. Consequently, disruption of circadian function results in severe dysfunctions and has been associated with various pathologies including cancer. Recent findings revealed intriguing links between the circadian system and another highly conserved biological system, the DNA damage response (DDR). Upon DNA damage, eukaryotic cells activate a complex signaling network to regulate cell cycle checkpoint arrest and/or apoptosis. At the core of the DDR are the ATM, ATR and DNA-PK kinases, which phosphorylate numerous downstream targets on preferred SQ motifs. We previously showed that the key circadian factor, Per1, associates with ATM and sensitize cells to DNA-damage induced apoptosis. In a recent screen, human Per1 Ser1263 was identified as a potential substrate for ATM/ATR. Per1 Ser1263 is part of a SQ motif conserved among mammalian Per1 proteins. To confirm that Per1 is phosphorylated on this site, we mutated murine Per1 Ser1264 (corresponding to human Ser1263) to alanine. 293T and HCT116 cells were transfected with either wild-type (WT) or S1264A mutant (SA) myc-tagged Per1 and treated with DNA-damaging agents. Western blot analysis demonstrated that Per1WT was recognized by phospho-specific SQ antibodies, while Per1SA was not. Furthermore, Per1 phosphorylation was significantly stronger in the treated cells. Interestingly, Per1 remained phosphorylated in ATM deficient cells. In contrast, silencing of ATR by shRNA in 293T cells attenuated Per1 phosphorylation. Immunoprecipitations experiments showed that both overexpressed and endogenously expressed Per1 associate with ATR. To examine the functional significance of Per1 phosphorylation, we transfected SKOV3 cells with either myc-Per1WT or myc-Per1SA, and monitored their cell-cycle progression and apoptotic response after DNA damage. Compared to control SKOV3 treated cells, Per1WT expression resulted in significant increased numbers of G2/M arrested and apoptotic cells. This increase was diminished by Per1S1264A mutation. Our findings implicate Per1 as an important ATM/ATR substrate, and emphasize the significance of proper circadian regulation to cell survival upon exposure to genotoxic stress.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3871.
Abstract 3893: Overexpression of FOXQ1 is important factor in tumorigenicity and tumor growth
Authors: Kaneda Hiroyasu , Arao Tokuzo , Tanaka Kaoru , Tamura Daisuke , Aomatsu Keiichi , Kudo Kanae , Sakai Kazuko , De Velasco Marco Antonio , Matsumoto Kazuko , Yoshihiko Fujita , Yamada Yasuhide , Tsurutani Junji , Okamoto Isamu , Nakagawa Kazuhiko , Nishio Kazuto , Nagai Tomoyuki , Furuta Kazuyuki 
Published: February 2011

Abstract
Forkhead Box Q1 (FOXQ1) is a member of the forkhead transcription factor family, and it has recently been proposed to participate in gastric acid secretion and mucin gene expression in mice. However, the role of FOXQ1 in humans and especially in cancer cells remains unknown.
We found that FOXQ1 mRNA is overexpressed in clinical specimens of colorectal cancer (28-fold / colonic mucosa). A microarray analysis revealed that the knockdown of FOXQ1 using siRNA resulted in a decrease in p21CIP1/WAF1 expression, and a reporter assay and ChIP assay showed that p21CIP1/WAF1 was one of target genes of FOXQ1. Stable FOXQ1-overexpressing cells (H1299/FOXQ1) exhibited elevated levels of p21CIP1/WAF1 expression and inhibition of apoptosis induced by doxorubicin or camptothecin. Although cellular proliferation was decreased in H1299/FOXQ1 cells in vitro, H1299/FOXQ1 cells significantly increased tumorigenicity (EGFP: 2/15, FOXQ1: 7/15) and enhanced tumor growth (437 ± 301 vs. 1735 ± 769 mm3, p&lt;0.001) in vivo. Meanwhile, stable p21CIP1/WAF1 knockdown of H1299/FOXQ1 cells increased tumor growth, suggesting that FOXQ1 promotes tumor growth independent of p21CIP1/WAF1. Microarray analysis of H1299/EGFP and H1299/FOXQ1 revealed that FOXQ1-overexpression upregulated several genes that have positive roles for tumor growth including VEGFA, WNT3A, RSPO2 and BCL11A. CD31 and TUNEL staining of the tumor specimens showed that FOXQ1-overexpression mediated the angiogenic and anti-apoptotic effect in vivo.
In conclusion, FOXQ1 is overexpressed in colorectal cancer and enhances tumorigenicity and tumor growth presumably through its angiogenic and anti-apoptotic effects. Our findings demonstrate that FOXQ1 is a new member of the cancer-related FOX family.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3893.
Abstract 3894: Regulation of VDUP1 expression in breast cancer cells by cyclopamine
Authors: Voigt Jeffrey M. , Bajaria Arjun , Dearborn Richard E. 
Published: February 2011

Abstract
VDUP1 (TXNIP) is a tumor suppressor protein that contributes to the regulation of cell proliferation through its role as an inhibitor of thioredoxin (TRX). VDUP1 expression is decreased in a variety of tumor cells relative to non-tumor cells and enforced expression of VDUP1 slows tumor cell growth. 1,25-Dihydroxyvitamin D3 (VD3) has long been known to increase VDUP1 expression in tumor cells, although the full extent of VDUP1 regulation is not known. Preliminary experiments with Drosophila mutants lacking Hedgehog (Hh) secretion suggested that VDUP1 expression could be regulated by the Hh signaling pathway. Experiments were conducted to determine the ability of cyclopamine (CYCLO), an inhibitor of Hh signaling, to regulate VDUP1 expression in breast cancer cells. MDA-231 and MCF-7 cells, grown in RPMI 1640 medium containing 10% fetal calf serum, were treated with CYCLO (5-20 μM) or vehicle (methanol) for 24-72 hrs. Using an anti-VDUP1 antibody, VDUP1 localization was determined by immunofluorescence staining of cells grown on gelatin-coated coverslips following fixation in 4% paraformaldehyde. VDUP1 expression in methanol-treated MDA-231 cells showed a greater expression of VDUP1 in nuclei, indicated by overlapping expression with the nuclear marker histone deacetylase, as compared to cytoplasm. Treatment with 20 μM CYCLO for 72 hours resulted in a decrease in nuclear VDUP1 expression, coupled with a dramatic increase in cytoplasmic VDUP1. This redistribution of VDUP1 from the nucleus to the cytoplasm was detected as early as 24 hours after initiation of treatment with 20 μM CYCLO and was also detected following treatment with 10 μM CYCLO for 72 hours. The CYCLO-induced decrease in nuclear VDUP1 was confirmed with Western blotting. In contrast, no such changes were detected in CYCLO-treated MCF-7 cells. To investigate the direct effect of CYCLO treatment on vdup1 promoter activity, a 1.7 kb fragment of the human vdup1 promoter was inserted upstream of a luciferase gene to generate a vdup1/pLuc plasmid. vdup1/pLuc was co-transfected into CYCLO-treated cells (20 μM), along with a β-galactosidase plasmid and luciferase activity was determined. CYCLO treatment of MDA-231 cells resulted in a significant decrease in luciferase activity, as compared to methanol-treated cells. No changes in luciferase activity were seen following similar experiments conducted with MCF-7 cells. These results demonstrate the novel finding that inhibition of Hh signaling alters both the level of VDUP1 expression and the intracellular distribution of VDUP1 in MDA-231 cells. Future experiments will be directed at determining the mechanisms responsible for the change in the subcellular distribution of VDUP1 seen following CYCLO treatment.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3894.
Abstract 3899: A coactivator role of CARM1 for the dysregulated β-catenin activity in colorectal cancer cell growth and gene expression
Authors: Ou Chen-Yin , Manegold Philipp , Kahn Michael , Stallcup Michael 
Published: February 2011

Abstract
Aberrant activation of Wnt/β-catenin signaling is recognized as a critical factor in the etiology of colorectal cancer. Evidence has suggested that dysregulated β-catenin activity is associated with the majority of colon cancers via activation of the expression of Wnt regulated oncogenes. In the nucleus, β-catenin regulates transcription by recruiting additional secondary coactivators. These secondary coactivators all have distinct and unique functions on Wnt/β-catenin target gene activation. For instance, CCAR1 (Cell Cycle and Apoptosis Regulator 1) has been shown to be important for the stable occupancy of β-catenin at the promoter of a Wnt target gene, and depletion of CCAR1 inhibits expression of several Wnt/β-catenin target genes and suppresses anchorage-independent growth of colon cancer cells (Ou CY et al. Journal of Biological Chemistry 2009;284(31);20629-20637).
Here, we show that CARM1 (coactivator-associated-protein-arginine-methyltransferase 1) interacts with β-catenin and positively modulates β-catenin-mediated gene expression. In colorectal cancer cells, which have constitutively high Wnt/β-catenin activity, depletion of CARM1 inhibits the expression of Wnt/β-catenin-mediated oncogenes and suppresses anchorage-independent growth. In colorectal cancer cells that do not have constitutively high Wnt/β-catenin activity, we found that activation of Wnt/β-catenin signaling by treatment with Wnt3a increased the expression of a subset of Wnt target genes. Utilizing these cells, we demonstrated that CARM1 is specifically required for the expression of these Wnt3a-induced targets. Upon Wnt3a stimulation, CARM1-dependent dimethylation of histone H3 arginine (Arg) 17, at a Wnt-regulated promoter, is associated with the recruitment of both β-catenin and CARM1. Arg17 dimethylation by Wnt3a ligands is compromised by CARM1 knockdown, whereas Wnt3a-induced β-catenin recruitment is not affected. Finally, in a nude mouse xenograft model, compared with CARM1 knockdown cells, wild type HT29 tumor xenografts grow significantly faster. We conclude that CARM1 is an important modulator of Wnt/β-catenin transcription and may represent a novel target for therapeutic intervention in cancers involving aberrantly activated Wnt/β-catenin signaling.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3899.
Abstract 3911: Dysegulation of Sox9-dependent gene expression leads to enhancement of angiogenesis and metastases in pancreatic cancer
Authors: Camaj Peter , Ischenko Ivan , Seeliger Hendrik , Krebs Stefan , Renner Andrea , Jauch Karl W. , Bruns Christiane J. 
Published: February 2011

Abstract
Background: The understanding of invasion, angiogenesis and metastasis is essential for the development of new targeted molecular therapy against pancreatic cancer. The aim of this study is to analyse the regulation of differentially expressed genes in highly proangiogenic and prometastatic compared to low metastatic and low angiogenic pancreatic cancer cells
Materials and methods: The transcriptome of the low metastatic pancreatic cancer cell line and its highly angiogenic and metastatic derivate L3.6pl have been compared under the normoxic and hypoxic conditions using Affymetrix HGU133plus 2.0 arrays. The hierarchic cluster analysis has been performed using SOTA algorithm. Promoters of the differentially expressed genes have been analysed using oPOSSUM 2 program. Affymetrix data have been validated via qRT-PCR and via ELISA. Chromosomal DNA containing promoters of the relevant genes has been amplified via PCR and sequenced.
Results: The Affymetrix analysis revealed clusters of differentially regulated genes with regard to the cell line and the oxygen level. While VEGF expression was upregulated in FG cells under hypoxic condition, it was constitutively upregulated already under normoxic conditions in L3.6pl and no further stimulation was observed under hypoxic conditions. This regulation pattern was similar in a cluster of genes that share a promoter sequence coding for a binding site for the transcription factor Sox9. Sox9 itself shows a similar regulation, leading to the assumption that expression changes of Sox9 are involved in the different hypoxic gene expressions. Promoter analysis of Sox9 in FG and L3.6pl cells showed mutations in the promoter region in L3.6pl, while the VEGF promoter was unchanged. Further analysis has shown that this mutation is not relevant for biological function. Refined analysis revealed differential Sox9 promoter methylation as reason for observed phenomenon.
Conclusions: Proangiogenic genes such as VEGF are upregulated in the more aggressive cell line L3.6pl, compared to FG. We identified a gene cluster that is constitutively upregulated in L3.6pl, independent of hypoxia. These genes are controlled by the transcription factor Sox9. A Sox9 promoter differential methylation may be the reason for the escape from hypoxic regulation in L3.6pl cells and thus may contribute to the higher angiogenic and metastatic potential. Taken together, Sox9 may be an interesting new diagnostic and therapeutic target in pancreatic cancer progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3911.
Abstract 393: The SHrN™ scid hairless NOD mouse model: Development and characterization
Authors: Williams Shanice V. , Wildt Sheryl J. , Brooks Andrew I. , Cooper Dale M. 
Published: February 2011

Abstract
The SHrN™ scid hairless NOD mouse was developed to provide a hairless triple-immunodeficient mouse model to the research community. The non-obese diabetic (NOD) mouse carrying the Prkdcscid mutation (NOD scid mouse) is an established xenograft model for humanization, oncology, and immunology research. It has proven to be particularly useful in elucidating mechanisms of spontaneous lymphoma and thymic tumors, prostate cancer research, and the engraftment of hematopoietic stem cells. As scid mice are haired, it is often necessary to shave these mice to facilitate tumor observation and evaluation. However, shaving animals does not prevent autofluorescence of hair follicles while imaging scid mice. We have transferred the hairless mutation (Hrhr) from the outbred HsdOla:MF1-Hrhr to the NOD.CB17-Prkdcscid/NCrHsd mouse to generate the inbred hairless NOD.Cg-Prkdcscid Hrhr/NCrHsd mouse, or commonly named scid hairless NOD (SHrN™). Herein we describe the breeding program utilized to generate the SHrN™ model using marker assisted backcrossing methodology. A combination of single nucleotide polymorphism (SNP) allelic discrimination and quantitative PCR (QPCR) analysis was employed to genotype offspring for the Prkdcscid and Hrhr mutations. SNP genotypes were determined using the Fluidigm Biomark™ High Throughput SNP Genotyping Platform. In each backcross generation, a total of 560 SNPs was measured on all offspring homozygous for Prkdcscid and heterozygous for Hrhr to select the most optimal breeders with the highest percentage of NOD genetic background. Littermates identified to have a genetic background 99% concordant to the NOD mouse were sibling-mated to produce F1 breeders homozygous for both Prkdcscid and Hrhr mutations. The immunologic characteristics of this model are also described, which include B and T cell deficiency, a functional deficit of NK cells, and decreased macrophage and complement function. As the least leaky, most immunocompromised hairless model available, the SHrN™ model will become a valuable enhancement to oncology and immunology research, with particular benefit to imaging technology studies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 393.
Abstract 3936: Expression of DNA Repair Factor DDB2 predicts chemoresistance in various cancer cell lines
Authors: Takimoto Rishu , Murase Kazuyuki , Onuma Yoshiyuki , Hirakawa Masahiro , Yoshida Makoto , Sato Tsutomu , Sato Yasushi , Miyanishi Koji , Kobune Masayoshi , Kato Junji 
Published: February 2011

Abstract
Accumulating evidence suggests that DNA repair enzyme activity may predict sensitivity to chemotherapeutic agents in cancer cells. The status of a DNA repair enzyme, such as XPF/ERCC4 or XPD/ERCC2, has been reported to serve as a prognostic indicator as well as an indicator of chemosensitivity. Another such candidate is the protein product of the DDB2 gene, p48, that interacts with the p127 protein to form the UV-damaged DNA binding complex (DDB). DDB2, a DNA repair factor induced by tumor suppressor p53, plays an important role in the nucleotide excision repair (NER) of UV-damaged DNA. Mice lacking DDB2 developed spontaneous tumors at a high rate, suggesting a tumor suppression function for DDB2. In this study, we hypothesized that DDB2 expression correlated with sensitivity to chemotherapeutic agents. To this end, we compared the cytotoxicity levels of DDB2-expressing and non-expressing cell lines upon exposure to chemotherapeutic agents. As a result, downregulation of DDB2 using siRNA restored chemosensitivity. DDB2 may be a molecular marker for prediction of chemosensitivity and a new target molecule for cancer chemotherapy.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3936.
Abstract 3943: Oxidatively induced DNA base damage in non-small cell lung cancer
Authors: Senol Ozlem , Resmi Halil , Sevinc Can , Sanli Aydin , Onen Ahmet , Taylan Ebru , Dizdaroglu Miral , Kirkali Guldal 
Published: February 2011

Abstract
Non-small cell lung cancer (NSCLC) accounts for 80-85% of all cases of lung cancer and is known to be caused by smoking and other carcinogenic agents. Oxidatively induced DNA damage is involved in multiple modifications and mutations in DNA, thereby in pathogenesis of cancer as well as other diseases. In this study, we compared the tumor tissues to the surrounding healthy tissues obtained from 29 NSCLC patients who had undergone surgical resection. The levels of oxidatively induced DNA lesions such as 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua), 8-hydroxyguanine (8-OH-Gua) and (5′S)-8,5′-cyclo-2′-deoxyadenosine (S-cdA) were measured by gas chromatography/isotope-dilution mass spectrometry and liquid chromatography/isotope-dilution mass spectrometry. We found that the level of S-cdA was statistically significantly greater in cancer tissues than that in control tissues (p=0.0063), whereas the levels of FapyGua and 8-OH-Gua showed no significant difference between the two groups. There was no significant correlation between DNA damage and age, smoking or pathological stage. These results provide evidence for significant accumulation of S-cdA in tumor tissues compared to surrounding healthy tissues in NSCLC. The evaluation of the alterations in the levels of DNA lesions may contribute to the elucidation of the DNA repair defects in NSCLC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3943.