bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4137: Second generation alpha-helical stapled peptides efficiently reduce lymphoma cell viabilityby inhibiting LUBAC and NF-κB activity
Authors: Aguilar-Alonso Francisco A. , Whiting Amanda L. , Marshall Erin , Bernal Federico 
Published: July 2017

Abstract
The linear ubiquitin chain assembly complex (LUBAC) is the only known linear ubiquitin ligase whose function is dependent on the interaction of three proteins: HOIL, HOIP and SHARPIN. The activity of this ubiquitin ligase has been linked to a malignant phenotype associated with the activated B-cell (ABC) subtype of diffuse large B-cell lymphoma (ABC-DLBCL) through constitutive activation of the NF-κB pathway. A first generation of stapled peptides designed to inhibit LUBAC by intracellular disruption of the complex have been shown to reduce cell viability and NF-κB activity in ABC-DLBCL cells modestly. We have developed a second generation of stapled peptides based on the alpha-helical interaction interface of HOIP to enhance their ability to reduce LUBAC formation and, consequently, NF-κB activity as well as ABC-DLBCL cell viability. Live cell imaging showed that some of the second generation HOIP stapled peptides are cell permeable. Biochemical assays revealed that these peptides compromised cell viability, disrupted LUBAC complex formation and inhibited the NF-κB canonical pathway in ABC-DLBCL cell lines. Many of these new peptides were far more potent than any of the previously generated compounds that target the HOIL-HOIP binding interface. These findings support the hypothesis that these second generation peptides may be a useful tool as coadjuvants or therapeutic agents for the treatment of ABC-DLBCL.
Citation Format: Francisco A. Aguilar-Alonso, Amanda L. Whiting, Erin Marshall, Federico Bernal. Second generation alpha-helical stapled peptides efficiently reduce lymphoma cell viabilityby inhibiting LUBAC and NF-κB activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4137. doi:10.1158/1538-7445.AM2017-4137
Abstract 4206: A high-throughput 3D tumor spheroid screening method for drug discovery using imaging cytometry
Authors: Chan Leo Li-Ying , Cribbes Scott , Kessel Sarah , McMenemy Scott , Qiu Jean 
Published: July 2017

Abstract
There have been 1600 FDA approved drugs since their inception in 1938. Currently it costs approximately 883 million dollars to bring a drug candidate to the market, and often times the potential candidate fails at the beginning of the clinical phase. Therefore, it is important to develop drug screening methods that are more clinically relevant or predictable. The current 2D methods for cancer drug discovery have had some difficulty in identifying potential drug candidates that can be used for clinical testing. To overcome this challenge, there has been an increase in research of 3D tissue culture that facilitated the development of new in-vitro tumor model assays. Traditional 3D spheroid analysis method relied heavily on visual observation using standard microscopy, which is time-consuming and has high operator variations. In the recent years, high-throughput image-based cytometers, such as Celigo, have demonstrated the ability to perform bright-field and fluorescence cell-based assays. Celigo imaging cytometer can be employed to rapidly analyze and characterize 3D tumor spheroids, which can be used to generate both quantitative and qualitative results. In this work, we demonstrate a high-throughput 3D tumor spheroid screening method using the Celigo imaging cytometer to screen the effects of 14 drug compounds (NIH/NCAT) on U87MG spheroid size, matrigel invasion, and tumor spheroid viability. First, a dose response experiment is performed to screen the growth inhibitory effects of the drug compounds. In addition to direct spheroid size analysis, dose inhibitory responses of tumor invasion into the matrigel are also examined. Finally, the use of specific fluorescent dyes such as Calcein AM, PI, and Caspase 3/7 were used to screen drug induced cytotoxicity on the tumor spheroids. The results showed that Celigo imaging cytometer can quickly generate accurate growth inhibitory data to identify potential drug candidates. Furthermore, tumor invasion were clearly observed and quantified in the captured images, as well as fluorescent analysis of tumor spheroid viability. By utilizing the 3D spheroid screening method, researchers can rapidly characterize and quantify drug effects on tumor spheroids in a high-throughput format, which can improve the efficiency of identifying more qualified cancer drug candidates.
Citation Format: Leo Li-Ying Chan, Scott Cribbes, Sarah Kessel, Scott McMenemy, Jean Qiu. A high-throughput 3D tumor spheroid screening method for drug discovery using imaging cytometry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4206. doi:10.1158/1538-7445.AM2017-4206
Abstract 4208: Inhibition of proliferation and induction of apoptosis by a novel phytobiological mixture against breast cancer cell lines
Authors: Alqarni Afnan A. , Alamoudi Aliaa A. , Ajabnoor Ghada M. , Al-Abd Ahmed M. , Niedwiecki Aleksandra , Rath Matthias , Harakeh Steve 
Published: July 2017

Abstract
Breast cancer remains a leading cause of women’s death worldwide with progressive emergence of resistance towards approved chemotherapies. For this reason, new complementarytreatments have been sought. One of those includethe use of a phytobiological mixture against different types of malignancies, including but not limited to breast cancer. Herein, we investigated the anti-proliferative effects of a novel phytobiological mixture (PB)against two breast cancer cell lines :MDA-MB-231 and MCF-7.The PB mixture is composed of the following: quercetin, resveratrol, cruciferex, epigallocatechin-3-gallate and curcumin at different proportions. Theanti-proliferative and pro-apoptotic effects of PB were evaluated at non-cytotoxic concentrations as determined usingthe Sulfa-Rhodamine B assay (SRB).The effects of PB on the induction of apoptosis were valuated using Annexin-V and flow cytometry to measure the resultingDNA fragments. The results showed that at 72hrs, PB had cytotoxic effects against MDA-MB-231 and MCF-7 cells with an IC50’s of 25.8±5.4 µg/ml and 56.9±4.2 µg/ml, respectively. Exposure of MDA-MB-231 to PB for 72hrs resulted in the induction of apoptosis in a dose-dependent manner. PB concentrations of 10 µg/ml and 30 µg/ml, resulted in early programmed cell death of 9.1±1.5% and 22.1±1.8% respectively. Exposure to PB (10 µg/ml for 24 hrs) resulted in mild cell cycle arrest at the G2/M phase20.3±0.3% ;while higher dosesshowed a significant cell cyclearrest at theS-phaseas compared to the control untreated cells (p&lt;0.001). However, exposure to PB for 48 hrs at both doses,10 µg/ml and30 µg/ml,resulted in a significant cell cycle arrest at the S-phase 25.3±1.6% and 20.5± 0.4%respectivelyas compared to the control untreated cells 12.4±1.5% (p&lt;0.001). In conclusion, PB was found to have a promising anti-proliferative and pro-apoptotic effect in breast cancer cell lines. Further studies are needed to address the underlying mechanism of action of PB against breast cancer cell lines.
Citation Format: Afnan A. Alqarni, Aliaa A. Alamoudi, Ghada M. Ajabnoor, Ahmed M. Al-Abd, Aleksandra Niedwiecki, Matthias Rath, Steve Harakeh. Inhibition of proliferation and induction of apoptosis by a novel phytobiological mixture against breast cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4208. doi:10.1158/1538-7445.AM2017-4208
Abstract 4236: Gene expression profiling of prostate tissue identifies biological pathways associated with TMPRSS2:ERG gene fusion
Authors: Ebot Ericka , Isikbay Masis , Gerke Travis , Ahearn Thomas U. , Kelly Rachel S. , Tyekucheva Svitlana , Pettersson Andreas , Penney Kathryn L. , Mucci Lorelei A. 
Published: July 2017

Abstract
Background: TMPRSS2:ERG, a hormonally regulated gene fusion present in about half of prostate tumors, is the most common somatic event in prostate cancer. There is intriguing evidence to suggest that TMPRSS2:ERG-positive tumors may define a distinct subgroup of prostate cancer. In this study we compared gene expression profiles according to fusion status to identify genes and biological pathways differential expressed by TMPRSS2:ERG.
Methods: The study included men with prostate cancer in the Health Professionals Follow-up Study and the Physicians’ Health Study diagnosed between 1982 and 2004 and followed through 2012. Tumor biomarker data was available for archival tumor tissue from 380 cases, 191 of whom also had gene expression data for adjacent normal tissue. Whole genome mRNA expression profiling (20,254 genes) was performed using the Affymetrix 1.0 ST array. TMPRSS2:ERG tumor status was assessed by a genetically validated IHC assay for ERG. To relate expression of individual genes to ERG we used linear regression. Gene Set Enrichment Analysis (GSEA) was used to identify pathways of genes associated with ERG in both tumor and adjacent normal tissue. Data from The Cancer Genome Atlas (TCGA) was used to validate these findings.
Results: Among 380 cases, 186 (49%) of tumors were positive for the gene fusion.
Genome-wide differential expression analysis identified 492 genes upregulated and 369 genes downregulated in tumor tissue comparing ERG+ to ERG- tumors (FDR p-value &lt; 0.05). No genes were identified in the adjacent normal tissue at this significance level. 772 of the 861 genes (90%) identified in the HPFS/PHS dataset were confirmed in TCGA (448 upregulated and 324 downregulated). The top ten genes included ERG, WNK2, CACNA1D, HES1, SEPT9, PLA2G7, TDRD1, ANTXR2, SORBS2, and MYO6. Enrichment analysis identified a number of metabolic pathways associated with ERG tumor status including pathways involved in amino acid and fatty acid metabolism.
Conclusions: We identified significant differences in gene expression profiles in prostate tumor tissue according to TMPRSS2:ERG status, providing supportive evidence of this fusion as a unique subtype.
Citation Format: Ericka Ebot, Masis Isikbay, Travis Gerke, Thomas U. Ahearn, Rachel S. Kelly, Svitlana Tyekucheva, Andreas Pettersson, Kathryn L. Penney, Lorelei A. Mucci. Gene expression profiling of prostate tissue identifies biological pathways associated with TMPRSS2:ERG gene fusion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4236. doi:10.1158/1538-7445.AM2017-4236
Abstract 4241: Circulating microRNAs in plasma of men screened for prostate cancer
Authors: Mcdonald Alicia C. , Shen Jing , Vira Manish , Sanda Martin , Liao Jason , Lesser Martin L. , Patil Dattatraya , Raman Jay D. , Taioli Emanuela 
Published: July 2017

Abstract
Introduction: Although microRNAs (miRNAs) have been linked to prostate cancer risk, their role as a screening biomarker for prostate cancer (PC) has yet to be determined. We examined whether circulating miRNAs in plasma could be potential biomarkers for the early detection of PC among men undergoing prostate needle biopsy. Methods: Men who had a prostate biopsy due to an abnormal screening test were recruited. Demographics, medical history, clinical information, and blood processed into plasma were collected. TaqMan Low Density Arrays were used for the expression profiling of 733 miRNAs in plasma. Wilcoxon test was used to compare expression levels between men with and without a PC diagnosis. Logistic regression was used to examine the association between miRNAs and PC status, after adjusting for age and Bonferroni-correction. Results: There were 131 men, aged 46 to 86 years, included in the final analysis, with 66 men diagnosed with PC on prostate biopsy and 65 men without a PC diagnosis. Majority were white (72.5%) followed by black race (13.5%). Men with PC were older (median: 64 vs. 62 years; p-value = 0.16) and had statistically significantly higher serum PSA (median: 5.8 vs. 5.1 ng/mL; p-value = 0.01) compared to men without a PC diagnosis. The most statistically significant PC circulating miRNAs in plasma were miR-381, miR-523, miR-450B-5p, miR-34a, miR-34b, miR-639, and miR-365, after adjusting for age (p-values ≤ 0.05). The detection rate of these miRNAs in plasma ranged from 23.7% to 83.2%. These miRNAs were no longer statistically significant with PC diagnosis, after adjusting for multiple comparison (FDR q-value = 1.00). Conclusion: Among the 733 miRNAs evaluated, there was no miRNA found to be associated with PC diagnosis after adjusting for multiple comparison. Studies that examine a larger number of miRNAs which include the discovery of new miRNAs and their relationship with PC risk are warranted.
Citation Format: Alicia C. Mcdonald, Jing Shen, Manish Vira, Martin Sanda, Jason Liao, Martin L. Lesser, Dattatraya Patil, Jay D. Raman, Emanuela Taioli. Circulating microRNAs in plasma of men screened for prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4241. doi:10.1158/1538-7445.AM2017-4241
Abstract 4243: Epigenome-wide association study of metabolic syndrome in African-Americans
Authors: Akinyemiju Tomi 
Published: July 2017

Abstract
Background: The epidemic of obesity among US adults has resulted in significant increases in associated metabolic disorders such as diabetes, dyslipidemia and high blood pressure. Together, these disorders constitute metabolic syndrome, a clinically defined condition highly prevalent among African-Americans. Identifying epigenetic alterations associated with metabolic syndrome, including DNA methylation changes may provide information on biological pathways that are dysregulated and may potentially act as early biomarkers in cancer.
Methods: Data on cardio-metabolic risk factors and DNA methylation was assessed on 606 African-Americans from the Hypertension Genetic Epidemiology Network (HyperGEN) study. Metabolic syndrome was defined using the joint harmonized criteria of at least three of: elevated waist circumference, high triglycerides, low HDL-cholesterol, high fasting blood glucose and high blood pressure. DNA methylation was assessed using the Illumina HumanMethylation 450K Bead Chip assay on DNA extracted from buffy coat. Linear mixed effects regression models were used to examine the association between CpG methylation and metabolic syndrome in crude and adjusted (for age, alcohol, smoking, sex) analyses. Replication using DNA from 76 African-Americans in the REason for Geographic and Racial Disparities in Cancer (REGARDS) study, as well as meta-analysis combining both cohorts was conducted.
Results: Two differentially methylated CpG sites in the IGF2BP1 gene on chromosome 17 (cg06638433; β =0.01, p-value=3.10x10-7) and the ABCG1 gene on chromosome 21 (cg06500161; β: 0.018, p-value=2.60x10-8) were identified in models adjusted for age, sex, alcohol and smoking. Methylation of CpG sites on the TXNIP gene on chr 1 (p=2.83 x 10-9), and CPT1A gene on chr 11 (p=1.39 x 10-4) were also significantly associated with metabolic syndrome in unadjusted models. Results for the ABCG1 gene remained statistically significant in the replication set and meta-analysis.
Conclusion: Metabolic syndrome was consistently associated with focal DNA hypermethylation in the ABCG1gene, a region of the chromosome that encodes proteins in the ATP-binding cassette transporter family, and is involved intra- and extra- cellular signaling. Alterations in the ABCG1 gene was observed in 40% of invasive breast cancer tumors in the TCGA, providing a potential epigenetic link between metabolic syndrome and breast cancer that deserves further study.
Note: This abstract was not presented at the meeting.
Citation Format: Tomi Akinyemiju. Epigenome-wide association study of metabolic syndrome in African-Americans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4243. doi:10.1158/1538-7445.AM2017-4243
Abstract 4257: Dietary nutrient intake, ethnicity, and epigenetic silencing of lung cancer genes detected in sputum in New Mexican smokers
Authors: Leng Shuguang , Picchi Maria , Filipczak Piotr , Gilliland Frank , Belinsky Steven A. 
Published: July 2017

Abstract
Promoter hypermethylation of lung cancer (LC) genes detected in sputum assesses field cancerization and predicts LC risk. Hispanic smokers have greater risk for methylation than non-Hispanic Whites (NHW). We aimed to identify novel dietary nutrients affecting methylation of LC genes in sputum and determine the degree of ethnic disparity explained by diet. A cross-sectional population-based study was conducted with dietary intake assessed using a validated Harvard food frequency questionnaire in 327 Hispanics and 1502 NHWs from the Lovelace Smokers cohort (LSC). Twelve LC genes with diverse cellular functions whose concomitant methylation strongly predicted LC risk were studied. A global association was identified between dietary intake and gene methylation (Ppermutation=0.003). Seventeen nutrient measurements were associated with methylation with magnitude greater than seen for folate and these nutrients together accounted for 36% of the variance in methylation. Six protective nutrients were identified and their insufficient intake in Hispanics explained approximately 42% of ethnic disparity in methylation. Functional validation of protective nutrients that also explained ethnic disparity was provided by showing an enhanced DNA repair capacity towards double-strand DNA breaks, a mechanistic biomarker strongly linked to acquisition of LC gene methylation in smokers. Dietary intake is a major modifiable factor for preventing promoter methylation of LC genes in smokers’ lungs. Altering the diet in Hispanics may alleviate ethnic disparity for methylation. Complex dietary supplements could be developed based on these protective nutrients for LC chemoprevention in smokers. This study was funded by NIH R01 CA097356, NIH/NCI P30 CA118100, and the State of New Mexico as a direct appropriation from the Tobacco Settlement Fund.
Citation Format: Shuguang Leng, Maria Picchi, Piotr Filipczak, Frank Gilliland, Steven A. Belinsky. Dietary nutrient intake, ethnicity, and epigenetic silencing of lung cancer genes detected in sputum in New Mexican smokers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4257. doi:10.1158/1538-7445.AM2017-4257
Abstract 4271: Population-wide vs. carrier-probability-based BRCA1/2 mutation testing in the Washington Ashkenazi Study
Authors: Best Ana F. , Tucker Margaret A. , Katki Hormuzd A. 
Published: July 2017

Abstract
Background: Currently, women are referred for BRCA1/2 mutation testing if their family history of breast and ovarian cancer indicates they have sufficient probability of carrying mutations. In contrast, calls have intensified for population-wide testing for BRCA1/2 founder mutations among Ashkenazi Jews, due to relatively high mutation prevalence (2.5%) and decreasing genotyping costs. However, population-wide testing would strain genetic counseling resources and incur costs from testing mostly mutation-negative women. We compared the performance of population-wide vs. carrier-probability-based BRCA1/2 testing in the community-based Washington Ashkenazi Study (WAS).
Methods: BRCA1/2 carrier-probabilities based on reported family histories were calculated using BRCAPRO for 4589 probands (102 BRCA1/2 mutation-carriers) in WAS. For each carrier-probability threshold, we compared the percent of mutations found (sensitivity) vs. the percent of women requiring mutation testing, overall and by proband age. At example carrier-probability thresholds, undetected and detected carriers’ attributes were compared using nonparametric tests.
Results: A 1.2% carrier-probability threshold identified 80% of BRCA1/2 mutations in the 35% of women with highest carrier-probability. For women under age 40, 94% of BRCA1/2 mutations were identified in the 50% of women with highest carrier-probability. Compared to identified mutation-carriers, missed mutation-carriers had no personal cancer history, no affected first- and second-degree relatives (p&lt;0.0001), more unaffected first-degree relatives (p=0.0002), and were older (p=0.012; median age=53).
Conclusion: Carrier-probability-based BRCA1/2 mutation testing identified large majorities of mutation-carriers and would have avoided testing for many mutation-negative women. Missed mutation-carriers were older and cancer-free and would gain minimal benefit from risk-reducing interventions. A cost-effective carrier-probability threshold could acceptably tradeoff identifying BRCA1/2 mutation carriers before they get cancer while testing as few women as possible.
Citation Format: Ana F. Best, Margaret A. Tucker, Hormuzd A. Katki. Population-wide vs. carrier-probability-based BRCA1/2 mutation testing in the Washington Ashkenazi Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4271. doi:10.1158/1538-7445.AM2017-4271
Abstract 4300: Thymoquinone Inhibits Proliferation and induces apoptosis in leukemic cells
Authors: Harakeh Steve , Semaan Josiane , Sabban Marwan El , Jaouni Soad K. Al , Diab-Assaf Mona , Azar Rania 
Published: July 2017

Abstract
Introduction: Adult T-cell leukemia (ATL) is caused by human T-cell lymphotropic virus 1 (HTLV-1) and is an aggressive form of malignancy. So far, there is no effective treatment for ATL. Thymoquinone has been reported to exhibit many useful effects including anti-cancerous properties. Objective: The aim of this study is to investigated the effects of TQ on proliferation, apoptosis induction and the underlying mechanism of action in both HTLV-1 positive (C91-PL and HuT-102) and HTLV-1 negative (CEM and Jurkat) malignant T-lymphocytes. Materials and methods: Cells were treated with various concentrations of thymoquinone for 24h. Cell cytotoxicity was assayed using the CytoTox 96® Non-Radioactive Cytotoxicity Assay Kit. Cell proliferation was determined using CellTiter 96® Non-Radioactive Cell Proliferation. Cell cycle analysis was performed using staining with propidium iodide. Apoptosis was assessed using cell death ELISA kit. The effect of TQ on p53, p21, Bcl-2 protein expression was determined using Western blot analysis while TGF mRNA expression was determined by RT-PCR. Results: At non-cytotoxic concentrations of TQ, it resulted in inhibition of proliferation in a dose dependant manner. Flow cytometric analysis revealed a shift in the cell cycle distribution to the PreG1 phase which is a marker of apoptosis. Also TQ increased DNA fragmentation. TQ mediated its anti-proliferative effect and apoptosis induction by an up-regulation of TGFβ1, p53 and p21 and a down-regulation of TGF-α and Bcl-2α. Conclusion: Thymoquinone showed antiproliferative and proapoptotic potentials in ATL cells. For this reason, further research is required to investigate its possible application in the treatment of ATL.
Citation Format: Steve Harakeh, Josiane Semaan, Marwan El Sabban, Soad K. Al Jaouni, Mona Diab-Assaf, Rania Azar. Thymoquinone Inhibits Proliferation and induces apoptosis in leukemic cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4300. doi:10.1158/1538-7445.AM2017-4300