bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1827: Height, obesity and colorectal adenomatous polyps: The Minnesota Cancer Prevention Research Unit case-control study
Authors: Tu Huakang , Bostick Roberd M. 
Published: June 2012

Abstract
Background: Several observational studies found greater height and obesity to be associated with increased risk for colorectal cancer; however, there have been few studies of their associations with adenomatous polyps, precursors to most colorectal cancers.
Methods: We investigated the association of body size characteristics with risk of incident, sporadic colorectal adenomatous polyps using data from the Minnesota Cancer Prevention Research Unit case-control study of 566 colonoscopy-positive adenomatous polyp cases, 687 colonoscopy-negative controls, and 535 community controls conducted 1991-1994. Self-administered measurements of height, weight, and waist and hip circumferences were collected at recruitment. From these measurements, waist-to-hip ratio (WHR) and body mass index (BMI; kg of weight/height in m2) were calculated as indicators of obesity.
Results: In the multivariate analyses using the colonoscopy-negative controls, the adjusted odds ratios (OR) for adenomas across the upper three quartiles relative to the lowest quartile of height were 1.25 (95% confidence interval [CI]: 0.89, 1.76), 1.31 (95% CI: 0.93, 1.85), and 1.42 (95% CI: 0.96, 2.10), respectively; for WHR, the corresponding ORs were 0.82 (95% CI: 0.57, 1.18), 1.71 (95% CI: 1.15, 2.54), and 1.06 (95% CI: 0.75, 1.50); and for BMI they were 1.01 (95% CI: 0.70, 1.47), 1.28 (95% CI: 0.89, 1.82), and 1.20 (95% CI: 0.84, 1.70). For the combined effects of height and WHR and height and BMI, height, WHR, and BMI were dichotomized based on the median values among the community controls. Relative to those with shorter height and who also had a smaller WHR, those who were taller and also had a larger WHR were more likely to have adenomas (OR=1.71, 95% CI: 1.18, 2.48); the p-value for a multiplicative interaction was 0.68. Relative to those with shorter height and who also had a smaller BMI, those who were taller and also had a larger BMI were more likely to have adenomas (OR=1.50, 95% CI: 1.03, 2.19); the p-value for a multiplicative interaction was 0.72.
Conclusions: These data suggest that being taller and/or overweight may be associated with increased risk for colorectal adenomatous polyps.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1827. doi:10.1158/1538-7445.AM2011-1827
Abstract 184: HIPK2 downregulates Nox1 that is involved in p53Lys382 deacetylation and suppression of p53 oncosuppressor function
Authors: Puca Rosa , Nardinocchi Lavinia , D'Orazi Gabriellla 
Published: June 2012

Abstract
.HIPK2 is a stress-induced kinase and a transcriptional co-repressor that functionally cooperates with p53 to suppress cancer. Activation of the p53 proapoptotic function requires a cascade of phosphorylations and acetylations, and HIPK2 takes part in both modifications in that it phosphorylates Ser46 and allows Lys382 acetylation. In a cDNA microarray analysis we have found that depletion of HIPK2, that strongly affects p53 transcriptional function, induces Nox1 upregulation. Nox1, a homologue of the catalytic subunit of the superoxide-generating NADPH-oxidase is often overexpressed in tumors where triggers the angiogenic switch and induces genome instability by producing oxygen reactive species (ROS). However, the involvement of Nox1 in p53 regulation has never been addressed. We found that HIPK2 downregulated Nox1-luc promoter activity and that Nox1 upregulation, following HIPK2 silencing or Nox1 overexpression, inhibited drug-induced p53 Lys382 acetylation that strongly affected p53 apoptotic activity. P53Lys382 is a target of SirT1, a NAD-dependent deacetylase that is often upregulated in tumors and inhibits p53 apoptotic function. By the use of either small interfering RNAs to target SIRT1 or the SirT1 inhibitor nicotinamide we found that Nox1-dependent inhibition of p53 transcriptional activity was SirT1-dependent. Thus, Nox1 was unable to inhibit p53 when coexpressed with a SirT1 deacetylase-defective mutant (SIRT1HY) suggesting a link between Nox1 and SirT1 activity and a novel mechanism of SirT1 activation. Finally, recovery of HIPK2 function, by the use of Doxicyclin-induced conditional interference, downregulated Nox1 expression and reduced ROS production with rescue of p53Lys382 acetylation and p53 apoptotic activity. These findings suggest that Nox1 is a novel target of HIPK2 repressor function and is linked to p53 inactivation involving SirT1 activation and probably ROS production.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 184. doi:10.1158/1538-7445.AM2011-184
Abstract 1851: Dietary mixed tocopherols inhibit cell proliferation in mammary hyperplasia, suppress the expression of inflammatory markers, and upregulate PPARγ
Authors: Smolarek Amanda K. , So Jae Young , Thomas Paul E. , Lee Hong Jin , Paul Shiby , Dombrowski Anne , Wang Chung-Xiou , Kong Ah-Ng Tony , Reuhl Kenneth , Lee Mao-Jung , Yang Chung S. , Suh Nanjoo 
Published: June 2012

Abstract
Dietary intake of vitamin E, a fat-soluble vitamin, has been suggested to reduce cancer risk because of antioxidant properties. There are eight different forms of vitamin E which include four tocopherols (with a saturated phytyl tail) and four tocotrienols (with an unsaturated isoprenoid side chain) designated as α, β, γ, and Δ variants. Previous clinical and epidemiological studies on vitamin E and cancer have focused on α-tocopherol. However, γ-tocopherol has demonstrated greater anti-inflammatory and anti-tumor activity than α-tocopherol. This study assessed the potential chemopreventive activities of a tocopherol mixture containing 58% γ-tocopherol (γ-TmT) in an established rodent model of mammary carcinogenesis. Female ACI rats were utilized due to their sensitivity to 17β-estradiol to induce mammary hyperplasia and eventually mammary tumors. The rats were implanted subcutaneously with estradiol (E2) pellets containing 2.5 mg of E2 and given 0.3% or 0.5% γ-TmT in the diet for 2 or 10 weeks. Serum E2 levels were significantly reduced by the treatment with 0.5% γ-TmT. Serum levels of anti-inflammatory markers, prostaglandin E2 and 8-isoprostane, were suppressed by γ-TmT treatment. Histology of mammary glands showed evidence of epithelial hyperplasia in E2 treated rats. Immunohistochemical analysis revealed a decrease in estrogen receptor α (ERα) and proliferating cell nuclear antigen (PCNA), and an increase in cleaved-caspase3 and peroxisome proliferator-activated receptor γ (PPARγ) in the γ-TmT treated rats, indicating that tocopherol treatment inhibits cell proliferation and induces apoptosis. Treatment with γ-TmT resulted in a decrease in the expression of ERα mRNA, while ERβ and PPARγ mRNA levels were increased. These data suggest that γ-TmT inhibits the cell proliferation in mammary hyperplasia, suppresses the expression of inflammatory markers, and upregulates PPARγ. In conclusion, γ-TmT may be a promising agent for human breast cancer prevention.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1851. doi:10.1158/1538-7445.AM2011-1851
Abstract 2157: Cell cycle dependent regulation of c-Myb target gene specificity
Authors: Quintana Anita M. , Ness Scott A. 
Published: June 2012

Abstract
The c-Myb transcription factor is a critical regulator of proliferation and stem cell differentiation, and mutated alleles of c-Myb are oncogenic, but little is known about changes in c-Myb activity during the cell cycle. Previous studies have shown that the specificity of c-Myb depends in part on its DNA binding domain, but also on protein-protein interaction motifs in the C-terminal regulatory domains of the protein. These interactions are likely subject to regulation by post-translational modifications and are modified in oncogenic derivatives of c-Myb, which regulate different sets of target genes than the normal c-Myb protein. The analysis of cell cycle regulated target genes provides an ideal means of following the regulation of c-Myb activity in different subsets of cells that are in distinct cell cycle phases. Using Chromatin Immunoprecipitation (ChIP) assays, we found that c-Myb associated with some target genes only in specific cell cycle stages. For example, with the Cyclin E1 gene promoter only in G2/M phase cells. However, we also found that the levels of c-Myb protein were dramatically affected by treating with some cell cycle blocking agents. To map the association of c-Myb with specific target genes during the cell cycle, we developed a novel Fix-Sort-ChIP approach, in which asynchronously growing cells were fixed with formaldehyde, stained with Hoechst 33342 and separated into different cell cycle fractions by flow sorting, then processed for ChIP assays. This approach showed that the specificity of c-Myb is dramatically different in small subpopulations of cells, for example cells in the G2/M phase of the cell cycle, than in the bulk population. The repositioning of c-Myb during the cell cycle is not due to changes in its expression and also occurs with ectopically expressed, epitope-tagged versions of c-Myb. The repositioning occurs in established cell lines, in primary human CD34+ hematopoietic progenitors and in primary human acute myeloid leukemia cells. Our results suggest that c-Myb specificity is actively regulated during the cell cycle, probably through changes in protein-protein interactions. This sheds new light on the dynamic nature of gene regulation during the cell cycle and on the importance of post-translational modifications and/or oncogenic mutations that can dramatically alter the activity and the specificity of transcription factors like c-Myb.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2157. doi:10.1158/1538-7445.AM2011-2157
Abstract 2168: Detections of olfactomedin 4 gene expression by qRT-PCR in human prostatic samples and cell lines
Authors: Li Hongzhen , Liu Wenli , Zhu Jianqiong , Rodriguez-Canales Jaime , Hanson Jeffrey C. , Emmert-Buck Michael R. , Rodgers Griffin P. 
Published: June 2012

Abstract
The human olfactomedin 4 gene (OLFM4) encodes an olfactomedin-related glycoprotein. OLFM4 gene is normally expressed in a limited number of tissues, including the prostate, but the regulation of OLFM4 gene expression in prostate are largely unknown. We have previously reported that reduced or lost expression of OLFM4 protein is correlated with higher Gleason scores in prostate cancer and loss of gene expression is due to deletions within the OLFM4 gene in about 36.7% (11/30) of prostate cancer patient samples studied. In this study, we investigated the regulation of OLFM4 gene expression in human prostate cancer pathogenesis.
We have investigated the mRNA expression levels using quantitative RT-PCR analysis in 144 human prostate cDNA samples (OriGene). We found that the average expression level of OLFM4 gene is significantly reduced in cancer tissues compared with normal tissues. The expression level of OLFM4 mRNA is inversely corrected with higher Gleason Score in prostate cancer. Interestingly, we also found higher expression of OLFM4 gene within small subset of samples with inflammation including prostatitis, hyperplasia and well differentiated tumor tissue.
We have also screened the expression of OLFM4 mRNA level using qRT-PCR in primary cultured human normal prostate epithelial cells (PREC), benign immortalized prostate epithelial cell (RWPE1), androgen-responsible cancer cells (LNCaP and VCaP), androgen-independent cancer cells (PC-3 and DU145). We found lower expression of OLFM4 in RWPE1 cells. We also confirmed our previous results that OLFM4 mRNA was not expressed in cancer cell lines, LNCaP, VCaP, PC-3 and DU145.
We have reported previously that deletions within the OLFM4 gene were present in about 40% in human prostate cancer samples studied. To test whether methylation is also involved in the loss of OLFM4 gene expression in human prostate cancer, the methylation status of CpG sites in OLFM4 promoter region has been analyzed in primary prostate tissues obtained by Laser Capture Microdissection. Hypermethylation of CpG sites at -91, -486 and -681 were detected in higher Gleason score of cancer samples. We further treated PC-3 cells (in which the OLFM4 gene is intact) using the demethylation reagent, 5-aza-2’-deoxycytidine and found restoration of OLFM4 mRNA expression. The results suggest that methylation status of OLFM4 gene promoter region may affect OLFM4 gene expression in prostate cancer cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2168. doi:10.1158/1538-7445.AM2011-2168
Abstract 2184: Complex formation between the DLC1 START domain and Cav1 contributes to the tumor suppressor function of DLC1
Authors: Du Xiaoli , Qian Xiaolan , Papageorge Alex , Vass William C. , Braverman Richard , Lowy Douglas R. 
Published: June 2012

Abstract
Deleted in live cancer (DLC1), a tumor suppressor gene with Rho GTPase-activating (RhoGAP) activity, is frequently inactivated in a variety of cancers. DLC1 encodes a 1091 amino acid multi-domain protein whose RhoGAP catalytic domain (aa 609-878) is flanked by an amino-terminal sterile alpha motif (SAM; aa 17-76) and a carboxy-terminal steroidogenic acute regulatory (StAR)-related lipid transfer (START; aa 879-1080) domain. Caveolin-1 (Cav1), a key constituent of caveolae, plays an important role in signal transduction, endocytosis, and cholesterol transport, behaves as a tumor suppressor in most contexts, and is reported to form a complex with DLC1. Here, we have sought to assess the biological relevance of the DLC1-Cav1 interaction and to determine the region of DLC1 that interacts with Cav1.
After confirming that endogenous DLC1 and Cav1 co-localize with each other by immunomicroscopy and form a complex in vivo as assessed by co-immunoprecipitation, we determined the DLC1 sequences that were required for complex formation. Using GST-Pull down of a GST-Cav1 fusion protein that had been co-transfected with a series of GFP-DLC1 fragments, we identified a polypeptide of DLC1 (aa 899-996), composed of residues from the START domain that was necessary and sufficient for complex formation. A full-length GFP-DLC1 mutant lacking some of these START residues (aa 929-957) was deficient for complex formation with endogenous Cav1. When stably expressed in a human lung cancer cell line that did not express endogenous DLC1, the mutant was severely compromised in suppressing cell migration, colony formation, and anchorage-independent growth in soft agar compared to cells stably expressing the wild type GFP-DLC1. We conclude that the START domain of DLC1 is required for its complex formation with Cav1, and that this interaction contributes to the tumor suppressor activity of DLC1. To our knowledge, this is the first identified function for the DLC1 START domain.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2184. doi:10.1158/1538-7445.AM2011-2184
Abstract 2188: Effect of the protein complex formation of a novel tumor suppressor HLJ1 and nuclear protein p54nrb on human lung adenocarcinoma cell migration and invasion
Authors: Lin Sheng-Yi , Chen Ching-Hsien , Yu Sung-Liang , Wang Chi-Chung , Chang Gee-Chen , Chen Jeremy J. W. 
Published: June 2012

Abstract
Lung cancer is the most common cause of cancer deaths in the world, and the incidence is increasing each year. In the previous studies, we have identified and characterized a novel tumor/invasion suppressor gene HLJ1 (human liver DnaJ-like protein, also called DNAJB4) in a lung cancer cell line model with different invasion capability. However, the suppressive mechanism of HLJ1 is unclear. Therefore, the objective of this study is to investigate and characterize the proteins interacting with HLJ1. To obtain the novel HLJ1-binding protein, the differentially cultured density of tumor cell is employed to mimic metastatic characteristics in vitro. We identified two proteins, p54nrb and PSF, that can interact with HLJ1 in high cell culture density by immunoprecipitation assay and MALDI-TOF analysis. The complex of HLJ1 and p54nrb was confirmed in vitro and in vivo by co-immunoprecipitation, GST pull-down and mammalian two-hybrid assay. In addition, the results of GST pull-down assay indicated that p54nrb can interact with HLJ1 through HTH motif. We also found that the expressions of both HLJ1 and p54nrb are increased in A549, CL1-0, CL1-5 and CL1-5F4 cancer cell lines while are culturing in high cell density. The results of immunofluorescent staining and cytosolic/nuclear protein fraction revealed that p54nrb is mainly located in the nucleus. Furthermore, we found that over-expression of p54nrb protein in the highly invasive lung cancer cell line, CL1-5, can reduce cancer cell proliferation, colony formation, invasion and migration. On the other hand, p54nrb was decreased when most cells are in DNA synthesis phase. Once over-expression of p54nrb in CL1-5 cell line, the cell cycle would arrest in G1 phase to reduce cancer cell proliferation. Investigating the action mechanism of HLJ1-p54nrb interaction is important, it may not only provide a new insight to understand the pathway of metastasis and growth regulation but also be as the new target molecule for anti-cancer therapy in the future.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2188. doi:10.1158/1538-7445.AM2011-2188
Abstract 2193: Application of a novel cell-based dual luciferase assay to identify inducers of the tumor suppressor RhoB
Authors: Saber Barbara , Zhang Chunyu , Wilson WIllie , Gills Joell , Dennis Phillip 
Published: June 2012

Abstract
RhoB is a small GTPase tumor suppressor whose expression is commonly repressed during tumorigenesis by mechanisms such as Akt activation, HDAC1-mediated histone modification and/or specific microRNAs such as miR-21 overexpression. Forced expression of RhoB inhibits cell proliferation, survival, invasion and metastasis. Because RhoB is rarely mutated or deleted in human tumors, its restoration may have therapeutic benefit. Therefore, a dual-luciferase high throughput assay was developed to monitor induction of RhoB transcription. Four different cancer cell lines were stably transfected with a single vector in which firefly luciferase and a fusion protein of renilla luciferase/neomycin resistant gene were driven by RhoB or CMV promoters, respectively. These cell lines were screened in 96-well format with the NCI Diversity Set II library (1364 compounds). Induction of RhoB activity was compared to that caused by a known RhoB inducer (NSC126188), an HDAC inhibitor (TSA), a farnesyltransferase inhibitor (L744832), and an Akt inhibitor (PIA23). Seven compounds were identified, and induction of RhoB transcription and translation was validated under different serum conditions at several time points. They were also screened in secondary assays that included inhibition of Akt, induction of protein acetylation, and screening in a cancer cell line that cannot induce endogenous RhoB due to a homozygous deletion of chromosome region 2p24. One compound caused sustained induction of endogenous RhoB in multiple cell lines under different conditions, and inhibited cellular proliferation and migration. These studies show that this assay system can identify specific RhoB inducers with potential anticancer activity, and suggest that it can be expanded to screen larger compound libraries, or be adapted to monitor transcriptional activation of other tumor suppressor genes.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2193. doi:10.1158/1538-7445.AM2011-2193
Abstract 2198: Role of SLC5A8, a plasma membrane transporter and a tumor suppressor, in the antitumor activity of dichloroacetate
Authors: Babu Ellappan , Thangaraju Muthusamy , Ganapathy Vadivel 
Published: June 2012

Abstract
Introduction: There has been growing interest among the public and scientists in dichloroacetate as a potential anticancer drug. Credible evidence exists for the antitumor activity of this compound, but high concentrations are needed for significant therapeutic effect. Unfortunately, these high concentrations produce detrimental side effects involving nervous system, hence precluding its use for cancer treatment. The mechanistic basis of the compound's antitumor activity is its ability to activate pyruvate dehydrogenase complex through inhibition of pyruvate dehydrogenase kinase. Since the compound inhibits the kinase at micromolar concentrations, it is not known why therapeutically prohibitive high doses are needed for suppression of tumor growth. We hypothesized that lack of effective mechanisms for the entry of dichloroacetate into tumor cells may underlie this phenomenon.
Methods: The transport of acetate and its chloro derivatives by human SLC5A8 was studied using the X. laevis oocytes expression system. The human transporter was expressed in oocytes heterologously by injection of SLC5A8 cRNA. The transport function was monitored electrophysiologically by the two-microelectrode voltage-clamp technique. Breast, colon and prostate cancer cell lines were transfected with SLC5A8 and expression was monitored by RT-PCR analysis. Intracellular levels of pyruvate and HDAC activity was also monitored in these cell lines.
Results: SLC5A8 transports dichloroacetate very effectively and with high affinity. This transporter is expressed in normal cells, but the expression is silenced in tumor cells via epigenetic mechanisms. The lack of the transporter makes tumor cells resistant to the antitumor activity of dichloroacetate. However, if the transporter is expressed in tumor cells ectopically, the cells become sensitive to the drug at low concentrations. This is evident in breast cancer cells, colon cancer cells, and prostate cancer cells. Normal cells, which constitutively express the transporter, are however not affected by the compound, indicating the tumor cell-selective therapeutic activity. The mechanism of the antitumor activity of the compound depends on its ability to inhibit pyruvate dehydrogenase kinase and force mitochondrial oxidation of pyruvate.
Conclusions: The silencing of SLC5A8 in tumors involves DNA methylation and its expression can be induced by treatment with DNA methylation inhibitors. Our findings suggest that combining dichloroacetate with a DNA methylation inhibitor would offer a means to reduce the doses of dichloroacetate to avoid detrimental effects associated with high doses but without compromising antitumor activity.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2198. doi:10.1158/1538-7445.AM2011-2198