bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-22: P53 genetic polymorphisms, interactions with lifestyle factors and lung cancer risk in a Chinese population.
Authors: Li Yanli , Chang Shen-Chih , Niu Rungui , Liu Li , Crabtree-Ide Christina R. , Zhao Baoxing , Shi Jianping , Han Xiaoyou , Li Jiawei , Su Jia , Cai Lin , Yu Shunzhang , Zhabg Zuo-Feng , Mu Lina 
Published: August 2014

Abstract
Background: A GWAS study suggested rs2078486 was a novel functional p53 SNP, but very few studies replicate this association. P53 rs1042522 is the most commonly studied SNP, but very few studies examined its potential interaction with environmental factors in relation to lung cancer risk. This study aims to examine associations between two p53 single-nucleotide polymorphisms (SNPs) (rs2078486, rs1042522), their potential interaction with environmental factors and risk of lung cancer.
Methods: A case-control study was conducted in Taiyuan, China. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Multiplicative and additive interactions between p53 SNPs and lifestyle factors were evaluated.
Results: Variant p53 rs2078486 SNP was significantly associated with elevated lung cancer risk among smokers (OR: 1.70, 95% CI: 1.08 - 2.67) and individuals with high indoor air pollution exposure (OR: 1.51, 95% CI: 1.00-2.30). Significant or borderline significant multiplicative and additive interactions were found between p53 rs2078486 polymorphism with smoking and indoor air pollution exposure. The variant genotype of p53 SNP rs1042522 significantly increased lung cancer risk in the total population (OR: 1.57, 95% CI: 1.11-2.21), but there was no evidence of heterogeneity among individuals with different lifestyle factors.
Conclusion: This study confirmed that p53 rs2078486 SNP is potentially a novel functional p53 SNP that may affect lung cancer risk. Our study also suggested potential synergetic effects of p53 rs2078486 SNP with smoking and indoor air pollution exposure on lung cancer risk.
Citation Format: Yanli Li, Shen-Chih Chang, Rungui Niu, Li Liu, Christina R. Crabtree-Ide, Baoxing Zhao, Jianping Shi, Xiaoyou Han, Jiawei Li, Jia Su, Lin Cai, Shunzhang Yu, Zuo-Feng Zhabg, Lina Mu. P53 genetic polymorphisms, interactions with lifestyle factors and lung cancer risk in a Chinese population. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-22. doi:10.1158/1538-7445.AM2013-LB-22
Abstract LB-220: The Integrinβ1/Src/Akt-driven bypass signaling pathway contributes to Erlotinib resistance in lung cancer.
Authors: Ono Mayumi , Kanda Rina , Watari Kosuke , Kawahara Akihiko , Kage Masayoshi , Uramoto Hidetaka , Kuwano Michihiko 
Published: August 2014

Abstract
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib and erlotinib have improved therapeutic efficacies on non-small cell lung cancer (NSCLC) harboring activating EGFR mutations. However, appearance of drug resistant mutation limits patients' outcome. A secondary T790M mutation and MET amplification are two major mechanisms of acquired EGFR-TKI resistance.
To develop novel therapeutics to overcome drug resistant tumors, we should further understand other mechanisms at molecular basis of intrinsic importance.
We established erlotinib or gefitinib resistant cell lines from PC9 cells that harbor an activating EGFR deletion mutation by chronic exposure to these TKIs. We have previously identified that loss of PTEN or loss of activated EGFR gene allele is responsible for acquired resistance (Cancer Res., 2010; Nat Med., 2011; PLoS ONE, 2012; Cancer Sci., 2013). In our present study, one erlotinib-resistant subline from PC9 cells revealed following interesting characteristics;
[1] The increased expression of integrins β1, α2, and α5 was observed, along with enhanced adhesion and migratory activity in the resistant sublines.
[2] The increased expression and activation of Src was also observed.
[3] Interestingly, integrinβ1 knockdown markedly restored sensitivity to erlotinib and reduced the activation of Src and Akt upon treatment with erlotinib.
[4] Furthermore, Src knockdown suppressed Akt phosphorylation and cell growth, and this inhibitory effect was further augmented by erlotinib.
[5] The expression of integrins β1 and α5 was also observed in a refractory tumor sample from a lung cancer patient treated with erlotinib. Together, we will present our novel concept that integrinβ1/Src/Akt pathway represents a novel a bypass effector pathway for the acquisition of resistance to EGFR-TKIs.
Citation Format: Mayumi Ono, Rina Kanda, Kosuke Watari, Akihiko Kawahara, Masayoshi Kage, Hidetaka Uramoto, Michihiko Kuwano. The Integrinβ1/Src/Akt-driven bypass signaling pathway contributes to Erlotinib resistance in lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-220. doi:10.1158/1538-7445.AM2013-LB-220
Abstract LB-225: Resistance to paclitaxel in triple negative breast cancer cells is associated with ABCB1 overexpression and gene amplification, and can be reversed by anti-EGFR targeting.
Authors: Ahmadzadeh Elaheh , Przybytkowski Ewa , Aguilar-Mahecha Adriana , Basik Mark 
Published: August 2014

Abstract
Background: Due to the absence of expression of estrogen, progesterone and HER2 receptors, triple negative breast cancer (TNBC) patients do not benefit from targeted therapies. Therefore, chemotherapy remains the only treatment of choice for patients with TNBC. Despite initial clinical responses to chemotherapy, the majority of TNBC patients acquire resistance and develop progressive disease. There is little data about mechanisms of resistance to chemotherapy in TNBCs.
Methods: We investigated the molecular mechanisms of acquired resistance to paclitaxel (PTX) in TNBCs. Four TNBC cell lines (BT20, SUM149, MA-MB-231 and MDA-MB-436) were cultured in the presence of increasing concentrations of paclitaxel until they acquired resistance. Gene expression and aCGH analysis were performed on all parental and resistant pairs.
Results: We found a novel amplification of the ABCB1 gene in BT20 and SUM149 resistant cell lines only. Gene expression analysis revealed significant up-regulation of expression of ABCB1 and EGFR ligands in SUM149 and BT20 resistant cells compared to parental cell lines. The functional activity of ABC transporters assessed using rhodamine 123 efflux assay demonstrated a marked increase in the efflux of rhodamine in SUM149-R and BT20-R which was reversed by verapamil. We treated resistant cells with two anti-EGFR drugs, lapatinib and neratinib, which are also known ABC transporter inhibitors, and found that both drugs inhibited rhodamine 123 efflux and restored sensitivity to PTX in these PTX-resistant TNBC cells.
Conclusion: This is the first report of ABCB1 gene amplification in paclitaxel resistant triple negative breast cancer cells. Our results suggest that ABCB1 gene amplification and EGFR ligand over-expression plays a critical role in the development of PTX resistance in TNBC cells, and that this resistance can be targeted by therapy with anti-EGFR agents. Thus, ABCB1 gene amplification and EGFR ligand expression may be novel predictive biomarkers for both chemotherapy and anti-EGFR therapy in TNBCs.
Citation Format: Elaheh Ahmadzadeh, Ewa Przybytkowski, Adriana Aguilar-Mahecha, Mark Basik. Resistance to paclitaxel in triple negative breast cancer cells is associated with ABCB1 overexpression and gene amplification, and can be reversed by anti-EGFR targeting. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-225. doi:10.1158/1538-7445.AM2013-LB-225
Abstract LB-234: A comparative genomic approach for identifying synthetic lethal interactions in human cancer.
Authors: Asiedu Michael K. , Deshpande Raamesh , Klebig Mitchell , Sutor Shari , Kuzmin Elena , Piotrowski Jeff , Shin Seung Ho , Costanzo Michael , Boone Charles , Wigle Dennis A. , Myers Chad L 
Published: August 2014

Abstract
Synthetic lethal interactions enable a novel approach for discovering specific genetic vulnerabilities in cancer cells that can be exploited for the development of therapeutics. This concept has recently been exploited in the development of PARP inhibitors as novel chemotherapeutics for breast cancer. While PARP is not essential in normal cells, BRCA mutant cells are dependent on it for their survival. This led to the successful treatment of BRCA mutant tumors of the breast, ovary, and prostate with the oral PARP inhibitor, olaparib. Therapeutic strategies based on such synthetic-lethal (SL) interactions can enable drug targeting of cancer-specific alterations for otherwise undruggable tumor suppressors. Large-scale analyses of genetic interaction networks in model organisms like yeast suggest that disease-specific networks should not only give rise to destructive phenotypes (e.g. uncontrolled cell growth), but will also present unique vulnerabilities that can be exploited for novel therapies. Despite successes in model organisms such as yeast, discovering synthetic lethal interactions on a large scale in human cells remains a significant challenge. We have used a combination of computational and experimental approach whereby yeast interactions between human orthologs are filtered by cancer association and prioritized by genomic features, and candidates from the prioritized list are then validated in human cell lines using an RNA interference approach. As a proof of principle, we utilized this approach to discover two previously unknown synthetic lethal/sick interactions, one between SMARCB1 (yeast SNF5) and PSMA4 (yeast PRE9), and another between ASPSCR1 (yeast UBX4) and PSMC2 (yeast RPT1) based on shRNA double knock-down in normal human fibroblast cells. These interactions suggest potentially new therapeutic targets for SMARCB1 and ASPSCR1 mutated cancers, and more broadly, illustrate the potential of this cross-species approach.
Citation Format: Michael K. Asiedu, Raamesh Deshpande, Mitchell Klebig, Shari Sutor, Elena Kuzmin, Jeff Piotrowski, Seung Ho Shin, Michael Costanzo, Charles Boone, Dennis A. Wigle, Chad L Myers. A comparative genomic approach for identifying synthetic lethal interactions in human cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-234. doi:10.1158/1538-7445.AM2013-LB-234
Abstract LB-240: A novel approach to detecting RNA expression in living breast cancer cells.
Authors: Weldon Don , Su Kevin , Ko Alex , Johnston Grace , Hsu Matthew , Armstrong Lucas 
Published: August 2014

Abstract
When studying the complexities of cancer biomarkers, the ability to monitor gene expression within live cells that have become cancerous provides better insight than examining fixed or lysed tissues. However, monitoring RNA within intact cells can prove to be challenging with current techniques, which involve complex RNA isolation procedures that compromise cell viability. Further, amplification methods can create false positives or erroneously inflate differences. Here we describe a probe-based detection method that allows for the detection of ErbB-2 and EGFR mRNA levels across live intact SK-BR-3 breast cancer cells without the need for transfection reagents. The detection methodology is based upon an oligonucleotide gold nanoparticle conjugate capable of detecting intracellular levels of mRNA and miRNA in living cells. The probes enter the cell by means of the cell's native endocytosis machinery. Upon binding to the complementary target RNA sequence, a fluorescent signal (flare) is released, which allows the cells to be detected on any fluorescence analysis platform. In contrast to traditional RNA detection methods, since our technique allows for detection within live cells without altering their gene expression, the same cells that were profiled for EGFR and ErbB-2 expression could be sorted based on their specific mRNA content and subsequently further studied. Stimulation or treatments could then be performed on the previously profiled cells and assessed using probes for additional RNA markers or more traditional techniques such as antibody staining, qRT-PCR, or Array profiling. For this purpose, we combined immunostaining for cell surface EGFR with fluorogenic nanoparticle-based detection of EGFR mRNA in 4 breast cancer cell lines known to range in EGFR expression levels, and observed significant correlation for the signals in two-color flow cytometry. Thus, detecting RNA expression levels in live cancer cells with the ability to utilize the same cells in downstream testing gives researchers the ability to perform experiments which were previously thought to be impossible.
Citation Format: Don Weldon, Kevin Su, Alex Ko, Grace Johnston, Matthew Hsu, Lucas Armstrong. A novel approach to detecting RNA expression in living breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-240. doi:10.1158/1538-7445.AM2013-LB-240
Abstract LB-241: Silencing of microRNA-31 prevents esophageal neoplasia in zinc deficient rats.
Authors: Taccioli Cristian , Chen Hongping , Garofalo Michela , Jiang Yubao , Di Leva Gianpiero , Alder Hansjuerg , Middleton Justin , Smalley Karl J. , Bottoni Arianna , Costinean Stefan , Farber John L. , Croce Carlo M. , Fong Louise Y Y 
Published: August 2014

Abstract
Dietary zinc deficiency (ZD) is implicated in the pathogenesis of human esophageal squamous cell carcinoma (ESCC). microRNA-31 (miR-31) is overexpressed in human ESCC. In the rat a ZD diet promotes esophageal carcinogenesis by inducing cellular proliferation and changes in the expression of microRNA and mRNA, including overexpression of miR-31 and cancer-related proinflammation genes. Here we report that treatment of ZD rats with locked nucleic acid (LNA)-modified inhibitor of miR-31 (LNA-antimiR) prevents the development of a precancerous esophageal phenotype. Weanling rats were fed ZD or zinc-sufficient (ZS) diet for 5 weeks. Simultaneously, ZD rats were administered intravenously (twice a week) LNA-antimiR, LNA-scramble miR-31 or the vehicle saline. ZS rats received saline. Compared to ZS rats, LNA-scramble miR-31-treated or saline-treated ZD rats overexpressed miR-31 and displayed a highly proliferative and inflammatory esophageal phenotype. Treatment of ZD rats with LNA-antimiR reduced miR-31 expression in esophageal epithelia and circulating blood by ~60% and reversed the ZD-induced esophageal pathology, as evidenced by a thinned esophageal epithelium with reduced cell proliferation by PCNA immunohistochemistry and increased apoptosis by caspase-3/7 activity. Transcriptome analyses of esophageal epithelia demonstrated derepression of target mRNAs with miR-31 seed sites. In particular, Stk40 (a negative regulator of NF-κ? signaling) was demonstrated to be a bona fide miR-31 target. Using in situ hybridization and immunohistochemistry, miR-31 overexpression in ZD esophageal sections correlated with downregulation of STK40 protein, as well as with upregulation of an NF-κ? p65 - RAGE-S100A9 inflammatory pathway that in turn, was normalized by miR-31 silencing. Thus, silencing miR-31 prevents esophageal neoplasia. Overexpression of miR-31 promotes ESCC initiation by enhancing inflammation via STK40 - NF-κ? signaling. The data indicate that miR-31 may be a promising therapeutic target for improved ESCC diagnosis and prevention. Funding: National Institutes of Health grants U01 CA152758 to CMC and R01CA118560 & R21CA152505 to LYYF.
Citation Format: Cristian Taccioli, Hongping Chen, Michela Garofalo, Yubao Jiang, Gianpiero Di Leva, Hansjuerg Alder, Justin Middleton, Karl J. Smalley, Arianna Bottoni, Stefan Costinean, John L. Farber, Carlo M. Croce, Louise Y Y Fong. Silencing of microRNA-31 prevents esophageal neoplasia in zinc deficient rats. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-241. doi:10.1158/1538-7445.AM2013-LB-241
Abstract LB-25: Exploration of genome-wide circulating microRNA in hepatocellular carcinoma (HCC) - dysregulation of miR-483-5p and miR-150 as diagnostic marker.
Authors: Shen Jing , Wang Antai , Wang Qiao , Gurvich Irina , Siegel Abby B. , Remotti Helen , Santella Regina M. 
Published: August 2014

Abstract
The incidence of hepatocellular carcinoma (HCC) has doubled over the past 20 years in the United States (US). HCC prognosis is poor if not diagnosed and treated at an early stage. MicroRNAs (miRNAs) are a class of small non-coding RNAs that control gene expression by inhibiting translation or inducing cleavage of target messenger RNAs (mRNAs). miRNAs can regulate diverse biological processes including DNA repair, apoptosis, cell proliferation, differentiation and immune function. Circulating miRNAs in cell-free plasma/serum samples have been consistently observed to have high stability and resistance to storage/handling, suggesting their potential use as diagnostic biomarkers. We conducted a two-phase epidemiological case-control study to test the hypothesis that genome-wide dysregulation of circulating miRNAs differentiate HCC cases from controls. A total of 69 HCC patients and 69 controls were recruited and matched on age, gender and ethnicity. Taqman low density arrays were used to examine genome-wide miRNA expression, and quantitative RT-PCR was used to validate promising candidates. Sixty-six miRNAs were found to be significantly over-expressed in plasma of HCC cases compared to controls after adjusting for false discovery rate (p&lt;0.05). A volcano plot indicated that 7 miRNAs had over 2-fold case-control differences with p&lt;0.01. Four significant miRNAs (miR-150, miR-30c, miR-483-5p and miR-520b) detectable in all samples with varied expression levels were further validated in an expanded case-control study. MiR-483-5p was statistically significantly over-expressed in HCC cases compared with controls (3.25 vs. 0.54, p&lt;0.0001). MiR-150 was up-regulated in HCC, but the difference was not significant (5.66 vs. 5.29). The combination of plasma levels of miR-483-5p and miR-150 can significantly differentiate HCC cases from controls with an AUC of 0.850 (p&lt;0.0001). The sensitivity and specificity were, respectively, 63.8% and 85.5%. These preliminary data indicated the importance of dysregulated circulating miRNAs in hepatocarcinogenesis, and suggesting the possibility of using miR-483-5p and miR-150 as diagnostic biomarkers. Large prospective studies are necessary to replicate the current findings, and evaluate the panel of circulating miRNAs in improving early diagnosis of HCC.
Citation Format: Jing Shen, Antai Wang, Qiao Wang, Irina Gurvich, Abby B. Siegel, Helen Remotti, Regina M. Santella. Exploration of genome-wide circulating microRNA in hepatocellular carcinoma (HCC) - dysregulation of miR-483-5p and miR-150 as diagnostic marker. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-25. doi:10.1158/1538-7445.AM2013-LB-25
Abstract LB-253: TRAPing telomerase activity using droplet digital PCR.
Authors: Shelton Dawne , Regan Jack , Karlin-Neumann George , Lin Jue , Blackburn Elizabeth 
Published: August 2014

Abstract
The aim of this work was to develop a more sensitive and high throughput assay for measuring telomerase activity. Telomeres are the protective structures at the ends of chromosomes consisting of 6 bp repeat sequences. In young cells, these regions can be as long as 15kb and act as caps which protect the DNA ends. These ends naturally degrade with each passing cell division, usually losing 25-200 base pairs per division. Once they are shortened below a critical length (estimated to be 200-300 bp) the cells arrest and become senescent, or “old”. Telomeres can be thought of as a cellular or mitotic clock. Once the clock has wound down, the cells either die or pass through crisis and become immortal.
One of the mechanisms of immortality is the activation of the enzyme, telomerase. Telomerase is the endogenous reverse transcriptase responsible for adding repeats to telomeres, rewinding the clock and enabling a cell to continuously divide. Abundant telomerase activity is found in fetal and adult stem cells, germ cells, and cancer. It is also present at much lower levels in non-stem cells, such as immune cells, but these levels can be difficult to measure reliably.
The telomerase repeat amplification protocol (TRAP) measures the presence of active telomerase by measuring the activity of the enzyme on a starting DNA template, which is then amplified by PCR. For samples with abundant telomerase activity, SYBR qPCR assays provide high throughput. However, the current most sensitive method of detection still uses radioactivity, laborious PAGE sequencing gels, and densitometry to quantify telomerase.
Here we explore using droplet digital™ PCR (ddPCR™) to provide absolute quantification of telomerase activity. This was achieved through single-molecule counting of telomerase-extended templates that were partitioned into droplets, amplified by PCR and detected by fluorescence droplet flow cytometry. Analysis of control samples suggests ddPCR is at least an order of magnitude more sensitive than TRAP radiography and is more amenable to higher throughput analysis. We extend throughput, sensitivity, and the range of biological samples that can be analyzed for telomerase activity.
Citation Format: Dawne Shelton, Jack Regan, George Karlin-Neumann, Jue Lin, Elizabeth Blackburn. TRAPing telomerase activity using droplet digital PCR. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-253. doi:10.1158/1538-7445.AM2013-LB-253