bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-435: Regulation of emmprin in Kaposi's sarcoma-associated herpesvirus (KSHV)-infected cells: a novel strategy developed against KSHV-related diseases
Authors: Qin Zhiqiang , Dai Lu , Bratoeva Momka , Toole Bryan , Parsons Chris 
Published: July 2012

Abstract
Purpose: KSHV is a common etiologic agent for cancers arising in the setting of immune suppression, including Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). We recently reported that the KSHV-encoded latency-associated nuclear antigen (LANA) upregulates expression of the multifunctional membrane glycoprotein emmprin (Extracellular Matrix MetalloPRoteinase Inducer) and associated cell invasiveness and colony formation (Qin et al. Cancer Res. 2010; 70(10): 3884–9). The purpose of this study was to determine mechanisms for KSHV/LANA-induced transcriptional activation of emmprin, and whether these interactions affect emmprin-mediated signal transduction.
Experimental Design: We used co-IP, confocal microscopy, gene silencing, and overexpression of LANA deletion mutants to whether specific transcription factors (TF) interact with LANA and mediate LANA-initiated emmprin activation, as well as putative sites of LANA-TF interactions. Pharmacological inhibitors, gene transfer, immunoblots, qRT-PCR, ELISA and transwell assays were performed to assess how LANA-TF interactions impact emmprin-dependent intracellular signal transduction and downstream pathogenesis.
Results: We found that Sp1, a Zn finger TF, mediates LANA activation of emmprin transcription/protein expression and cell invasiveness. The N-terminal domain of LANA, containing a nuclear localization sequence, is necessary and sufficient for Sp1 activation of emmprin and co-localizes with Sp1 in the nucleus. Interestingly, we also found that emmprin-dependent activation of pro-migratory cytokines/chemokines and endothelial cell invasiveness following de novo KSHV infection is dependent upon KSHV induction of PI3K/Akt and ERK signaling, but not NF-κB pathway. Conclusions: LANA interactions with Sp1, and KSHV induction of Akt- and MAPK-dependent signaling, initiate transcriptional activation of emmprin and emmprin-dependent activation of pro-migratory cytokines release and cell invasiveness following KSHV infection. Ongoing experiments to clarify regulatory networks for emmprin activation in KSHV-infected cells may lead to identification of novel therapeutic targets for KSHV-related diseases.
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 LB-435. doi:10.1158/1538-7445.AM2011-LB-435
Abstract LB-437: ICA-1: A novel PKC-i inhibitor inhibits the proliferation of prostate cancer cells
Authors: Bhayankara Aravind P. , Patel Rekha , Win-Piazza Hla , Pillai Prajit , Acevedo-Duncan Mildred E. 
Published: July 2012

Abstract
Prostate cancers are highly lethal tumors and besides skin cancer, prostate cancer is the most common type of cancer among men in the United States. Approximately one third of men diagnosed with cancer each year will have prostate cancer. Certain prostate cancers are highly lethal tumors due to the emergence of therapy-resistant prostate cancer cells. PKC-iota (PKC-ι) is an oncogene and an atypical protein kinase C isoform that confers resistance to drug-induced apoptosis in cancer cells (J. Biol. Chem. 272; 44: 27521–27524). PKC is of special interest since it is overexpressed in prostate cancers (Proc Natl Acad Sci U S A. 106:16369–16374). The objective of the study was to investigate the effects of inhibiting PKC-ι on the proliferation of prostate cancer cells in-vitro. The methodology involved treating androgen sensitive LnCap cells and androgen independent Du-145 with the novel PKC-ι inhibitor [1H-imidazole-4-carboxamide, 5-amino-1-[2,3-dihydroxy-4-[(phosphonooxy) methyl]cyclopentyl]-[1R-(1α, 2β, 3 β, 4 α)] (ICA-1) that targets a unique sequence (amino acid residues 469–475) in the catalytic domain of PKC-ι. Cell viability and number was quantified 24–72 hours following addition of either vehicle control or ICA-1 by Trypan blue exclusion. Additional ICA-1 was not added to the cells following the initial treatment. Results showed that at 24 hours post treatment, ICA-1 decreased the proliferation of LnCap cells by 46% (10 μM) and 83% (20 μM). ICA-1 reduced the proliferation of Du-145 cells at 24 hours by 43% (10 μM) and 51% (20 μM). The overexpression of PKC-ι in prostate cancer and the anti-proliferative effects of ICA-1 may translate into using PKC-i detection as a biomarker to identify patients that may benefit from anti-PKC-ι therapy with ICA-1 for personalized medicine.
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 LB-437. doi:10.1158/1538-7445.AM2011-LB-437
Abstract LB-440: Global DNA hypomethylation is independently associated with clinical diagnosis of gastric cancer, inflammation severity, and metaplasia
Authors: Guerrero-Preston Rafael E. , Jahuira-Arias Martha , Gilman Robert , Soudry Ethan , Perez Jimena , Mancinelli Andrea , Unger Helen , Ili-Gangas Carmen , Brebi-Mieville Priscilla , Sidransky David 
Published: July 2012

Abstract
Background: DNA hypomethylation of repetitive elements has been shown to play a significant role in gastric carcinogenesis. However, Biomarker Development Trials on gastric mucosa that quantify global 5-methyl cytosine (5mC) content across repetitive and non-repetitive regions of the genome are lacking.
Methods: We utilized an ELISA-based approach to quantify the global DNA Methylation Index (GMI) in a gastric cancer case-control study. Quantification of global DNA methylation was obtained by differential methylation calculation of 5mC relative to global cytidine (5mC +C) in samples compared to a hypermethylated human genomic DNA control.
Results: A cohort of 209 patients, a slight majority of which were women (52%) with a mean age of 63 years, were diagnosed by endoscopy at three outpatient clinics in Perú. Utilizing the updated Sydney, 50 adenocarcinoma cases and 159 non-tumor controls were subsequently confirmed by pathologists. The GMI mean was significantly lower (p-value &lt; 0.0001) for clinically defined cases, mean = 3.6 (95% CI, 3.03, 4.07) compared to controls, mean = 6.2 (95% CI, 5.37,7.03). The GMI mean was also significantly lower (p-value = 0.0001) for cases defined by pathologists, mean = 3.7 (95% CI, 2.99, 4.39) compared to controls, mean = 5.6 (95% CI, 4.94, 6.34). In stratified analyses, we found the GMI mean to decrease as the severity of inflammation increased. The GMI mean was significantly lower (p-value =0.02) for moderate inflammation, mean = 4.7 (95% CI, 3.66, 5.72) compared to mild inflammation, mean = 6.4 (95% CI, 5.34,7.5). The GMI was also non-significantly reduced in patients with intestinal metaplasia, mean =4.81 (95% CI, 3.5,6.10) when compared to patients without metaplasia, mean = 5.96 (95% CI 5.09, 6.83).
Discussion: We have shown significant differential global DNA hypomethylation in the progression of gastric lesions through the multistep carcinogenesis stages leading to gastric cancer in a case-control study. In patients diagnosed as controls, global hypomethylation was shown to decrease as the levels of inflammation increased. Patients with intestinal metaplasia also had a lower GMI than those without metaplasia. GMI may be a potentially useful biomarker for clinical detection, inflammation severity, and disease progression in gastric cancer. These results should be replicated in a larger study.
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 LB-440. doi:10.1158/1538-7445.AM2011-LB-440
Abstract LB-444: Transforming growth factor beta polymorphisms and breast cancer survival among Chinese women
Authors: Beeghly-Fadiel Alicia C. , Zheng Wei , Lu Wei , Cai Hui , Long Jirong , Gao Yu-Tang , Delahanty Ryan J. , Cai Qiuyin , Shu Xiao-Ou 
Published: July 2012

Abstract
Aberrant transforming growth factor-beta (TGFB) signaling contributes to tumor progression. To clarify the role of TGFB pathway variants and breast cancer survival, we conducted a two stage study among 4,535 breast cancer patients recruited in two studies conducted in Shanghai, China. In Stage I, 111 variants in TGFB, TGFBR1, and TGFBR2 were evaluated for associations with disease-free (DFS) and overall survival (OS) among 2,923 participants with a median of 5.5 years of follow-up time after their cancer diagnosis. Nominally significant associations with either DFS or OS were found for 31 variants, which after considering linkage disequilibrium, were found to represent 13 independent loci. Stage II genotyping was conducted among 1,612 additional participants with a median follow-up time of 5.1 years; data was available for 11 loci. Genetic variants in 6 loci were not associated with breast cancer outcomes in Stage II. Variants in 4 loci showed associations in Stage II that were generally consistent, but did not reach statistical significance. One variant was significantly associated with overall breast cancer survival in both study stages, and overall and disease free survival in analyses of the two study stage samples combined. Specifically, women with two copies of the rare variant of TGFBR1 rs3773651 (GG) had increased hazards of recurrence or breast cancer specific mortality (HR: 2.05, 95% CI: 1.28–3.27) and overall mortality (HR: 2.44, 95% CI: 1.50–3.95) compared to women with one or more common alleles (AG, AA) in age adjusted analyses. Additional adjustment for disease stage, ER, PR, or treatment including surgery, chemotherapy, radiotherapy, and tamoxifen did not attenuate these effects. Further, the statistical significance of these associations was retained after consideration was made for multiple comparisons (DFS p-value 0.0027; OS p-value 0.0003). rs3773651 is located in intron six of TGFBR2, a TGFB ligand specific receptor critical for transduction of TGFB signaling. Our data support a role for individual variation in TGFBR2 in breast cancer survival outcomes; additional investigation is warranted.
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 LB-444. doi:10.1158/1538-7445.AM2011-LB-444
Abstract LB-445: Reappraisal of breast cancer incidence in the United States
Authors: Anderson William F. , Katki Hormuzd , Rosenberg Philip S. 
Published: July 2012

Abstract
Breast cancer incidence in the United States rose until 1999 then fell. This decline was most apparent among older women with easier-to-treat estrogen receptor (ER) positive tumors; reported incidence of more aggressive ER negative cancers was stable. However, these analyses did not account for missing ER data, which can reduce statistical power and more importantly bias the observed trends. We, therefore, developed an imputation method to correct for missing ER using a national sample of 379,323 breast cancers diagnosed from 1992 through 2007. After correction, current incidence of ER positive tumors was surprisingly similar to pre-1999 incidence, whereas ER negative cancers fell steadily by 1.8% per year. We show for the first time that the recent national decline in breast cancer overall reflects an unexpected drop in ER negative rates more than any changes in ER positive rates. These refined results challenge past interpretations and have the potential to better gauge breast cancer trends.
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 LB-445. doi:10.1158/1538-7445.AM2011-LB-445
Abstract LB-447: Non-steroidal anti-inflammatory drugs and brain cancer
Authors: Daugherty Sarah E. , Moore Steve , Pfeiffer Ruth , Park Yikyung , Rajaraman Preetha 
Published: July 2012

Abstract
Several case-control studies have suggested that non-steroidal anti-inflammatory drugs reduce risk for glioblastoma multiforme, a very aggressive form of brain cancer. Limited prospective investigations, on the other hand, have not observed an association between regular use of aspirin and brain cancer; however, these studies generally had small numbers of brain cancer, and did not investigate the association with NSAIDs by histologic subtype. We investigated the association between use of NSAIDs and glioma, and more specifically glioblastoma multiforme, in a large prospective study, the NIH-AARP Diet and Health Study. The frequency of aspirin and non-aspirin NSAID use one year prior to baseline was ascertained using a self-administered questionnaire. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models with age as the underlying time metric adjusted for sex, race, and history of heart disease. The analysis included 302,767 individuals, with 341 incident glioma and 257 glioblastoma multiforme cases. Preliminary results indicated no association between regular use (more than 2 times per week) of aspirin and risk of glioma (HR=1.16; 95% CI:0.87–1.56) or glioblastoma multiforme (HR=1.17; 95% CI:0.83–1.65) compared to never users. Null associations were also observed among regular non-aspirin NSAIDs users and risk of glioma (HR=0.90; 95% CI:0.65–1.25) and glioblastoma multiforme (HR=0.83; 95% CI:0.56–1.22) compared to never users. Our findings from this large prospective study do not support an inverse association between NSAIDs and risk of glioma or glioblastoma multiforme.
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 LB-447. doi:10.1158/1538-7445.AM2011-LB-447
Abstract LB-450: Gene expression of colonic submucosa differs between the inflammatory colitides. A possible reason for differences in IBD-associated CRC incidences
Authors: Schäffer Michael W. , Roy Tanusri Ghosh , Smith Joan C. , Wise Paul E. , El-Rifai Wael M. , Washington Mary K. , Schwartz David A. , Muldoon Roberta L. , Herline Alan J. , Moses Harold L. , Adunyah Samuel E. , M'Koma Amosy E. 
Published: July 2012

Abstract
Purpose: Differentiating ulcerative colitis (UC) and Crohn's colitis (CC) may be inaccurate in up to 30% of inflammatory bowel disease (IBD) cases due to overlapping features of these colitides. IBD-associated colorectal cancer (CRC) is frequently diagnosed in an advanced stage. Mass-spectrometric (MS) proteomic patterns found in colonic submucosa have been shown to discriminate UC and CC. To verify this, we aimed to conduct pilot gene expression analyses via microarray assessment of colonic submucosa. The significances of these genes to CRC initiation is as yet not been elucidated.
Methods: Laser capture microdissection of colonic submucosa from UC (n=8), CC (n=8), and normal (NL, n=8) samples was performed. The submucosal mRNA was extracted using the PicoPure(TM) RNA Isolation Kit. Comprehensive gene expression analysis of the pooled mRNA from each group was then performed using the Affymetrix GeneChip® Gene 1.0 ST Array System. To detect changes for UC, we compared UC to CC and UC to NL; and for CC, we compared CC to UC and CC to NL.
Results: 28,869 genes were represented on the array by 26 probes spread across the full length of each gene. When comparing UC to CC, 138 genes showed at least a 5-fold significant overexpression (p&lt;0.01) with 5 of these genes showing a greater than 30-fold overexpression (Table, all p&lt;0.0001). When comparing CC to UC, 5 different genes were overexpressed at greater than 30-fold change (Table, all p&lt;0.0001). The results of the comparisons of these highly overexpressed genes in UC and CC vs. NL is noted in Table.
Conclusions: Microarray assessments show significantly different gene overexpression in UC and CC colonic submucosa, with a few select genes showing dramatic overexpression. Preliminary results indicate that we have the tools in hand to successfully validate the results from the microarray analysis using TR-qPCR and immunohistochemistry (IHC). These genes may assist in delineation of the previously identified differentiating MS submucosal proteomic peaks, potentially facilitating protein biomarker identification to discriminate the inflammatory colitides. These genes may relate to CRC initiation.

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 LB-450. doi:10.1158/1538-7445.AM2011-LB-450
Abstract LB-451: Detection of urinary HE4 as a biomarker for epithelial ovarian cancer
Authors: Li Zhong-Qian , Radwan Rachel , Polkowski Julie , Raju Savitha , Falcone Katherine , Simamora Rebecca , Kettlety Timothy , Moore Richard G. , Barnes Grady 
Published: July 2012

Abstract
Human epididymis protein 4 (HE4) has been shown to be a promising serum biomarker for epithelial ovarian cancer (EOC). Recently, Hellstrom et al. reported the detection of HE4 in urine as a biomarker for ovarian neoplasms (Cancer Lett.2010;296:43–8). We investigated the feasibility of urinary HE4 in detection of EOC in a pilot study. METHODS: This retrospective study measured the HE4 levels in urine samples obtained from an institutional review board-approved sample bank. HE4 was measured with HE4 EIA (Fujirebio Diagnostics, Inc.). Creatinine was measured via colorimetric determination by the Jaffe Reaction and used to normalize the HE4 levels. Clinical diagnosis of the subjects was based on the pathological diagnosis. Single-point urine samples were analyzed from 232 subjects; 72 with EOC or low malignant potential tumors and 160 with benign disease. RESULTS: The medians of HE4 levels in subjects with EOC and with benign disease were 29833 pmol/L (95% Confidence Interval (CI): 21185–54728) and 8515 pmol/L (95% CI: 7077–9314) respectively. The medians of HE4/Creatinine ratios in subjects with EOC and with benign disease were 420 (95% CI: 269–491) and 75 (95% CI: 68–83), respectively. Both the medians of HE4 levels and HE4/Creatinine ratios in EOC subjects were significantly higher than that in subjects with benign disease (P&lt;0.0001 in Median test). Receiver operator characteristic (ROC) analysis showed that areas under the curve (AUC) were 0.87 for HE4/Creatinine ratio (95% CI = 0.81–0.92) and 0.83 for HE4 level (95% CI = 0.76–0.89). There was no significant difference between the AUC for HE4 level and HE4/Creatinine ratio (P&gt;0.05). Using the shoulder point of each ROC curve as the cut-off, the cut-off values were 152.5 for HE4/Creatinine ratio and 19161 pmol/L for HE4 level respectively. The sensitivity, specificity, positive predictive value and negative predictive value at the set cut-off values were 70.8% (95% CI = 58.9% – 81.0%), 93.1% (95% CI = 88.0% – 96.5%), 82.3% and 87.6% for HE4/Creatinine ratio, and 65.3% (95% CI = 53.1% – 76.1%), 89.4% (95% CI = 83.5% – 93.7%), 73.4% and 85.1% for HE4 level, respectively. Concordance rates versus clinical diagnosis were 86.2% for HE4/creatinine ratio and 81.9% for HE4 level. CONCLUSIONS: This pilot study demonstrated the utility of urinary HE4 level alone or HE4/Creatinine ratio as potential biomarkers for the detection of EOC. The HE4/Creatinine ratio appeared to be better than the HE4 level in correlating with the clinical pathological diagnosis of EOC.
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 LB-451. doi:10.1158/1538-7445.AM2011-LB-451
Abstract LB-457: Effect of naproxen and NO-naproxen on intestinal neoplasia in the Apc +/Min-FCCC mouse model
Authors: Chang Wen-Chi L. , Ferrara Christina M. , Cooper Harry S. , Mosier Stacy L. , Kaunga Esther , Grubbs Clinton J. , Lubet Ronald A. , Clapper Margie Lee 
Published: July 2012

Abstract
Recent efforts to improve the vascular and gastrointestinal safety of nonsteroidal anti-inflammatory drugs (NSAIDs) have included the addition of a nitric oxide-donating moiety. The ability of the common NSAID naproxen and nitric oxide (NO)-naproxen to inhibit azoxymethane-induced aberrant crypt foci in the rat colon has been demonstrated. However, the chemopreventive activity of these agents against spontaneous colorectal tumors has not been reported. The goal of the present study was to compare the ability of naproxen and NO-naproxen (low- and high-dose molar equivalents) to inhibit colorectal adenomas in a unique strain of mice (Apc+/Min-FCCC) that spontaneously develops multiple colorectal tumors. Male Apc+/Min-FCCC mice (50 days of age) were randomized (n = 17 per group) to receive control diet or diet supplemented with naproxen (132 or 400 ppm) or NO-naproxen (182 or 550 ppm) for 45 days. Body weights were recorded weekly and did not differ significantly among treatment groups. At sacrifice, small intestinal and colonic tissues were examined grossly and the entire colon was submitted for histopathologic analysis. Low-dose naproxen and low-dose NO-naproxen decreased the multiplicity of gross small intestinal adenomas by 70.3% (mean ± SEM – 9.9 ± 1.45, P = 0.04) and 64.0% (12.0 ± 1.9), respectively, as compared to that of control mice (33.3 ± 14.0). No additional benefit was obtained by administering a higher dose of either agent. Histopathologic analyses revealed that the incidence of colorectal adenomas in mice treated with naproxen (low dose – 70.6%; high dose – 64.7%) was significantly less than that of both control mice (100%) (P = 0.019 and 0.0076, respectively) and mice treated with NO-naproxen (low dose – 88.2% and high dose – 100%). Low-dose naproxen reduced the multiplicity of colorectal adenomas by 41.5% as compared to control (mean ± SEM, 1.8 ± 0.5, 3.1 ± 0.7, respectively), while the efficacy of all other treatments was less. Interestingly, treatment with high-dose naproxen caused a dramatic (89.3%) reduction in the multiplicity of microadenomas as compared to unsupplemented control diet. This study represents the first demonstration that naproxen can inhibit spontaneous colorectal adenomas in a controlled model system. The ability of naproxen to disrupt the formation of colorectal lesions early in the carcinogenesis process (microadenomas) provides strong support for its further development as a regimen for the chemoprevention of colorectal cancer in high-risk individuals. (Supported by NIH N01 CN-43309.)
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 LB-457. doi:10.1158/1538-7445.AM2011-LB-457