bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2554: Constitutive short telomere length and lung cancer risk: a large case- control study.
Authors: Sanchez-Espiridion Beatriz , Gu Jian , Chang David W. , Chang Joe Y. , Lu Charles , Roth Jack A. , Wu Xifeng 
Published: August 2014

Abstract
Background: Telomeres plays a key role in the maintenance of chromosomal stability and integrity. Telomere dysfunction is a common crucial event in malignant transformation and tumorigenesis. Short telomere length in surrogate tissues (peripheral blood leukocytes, or PBLs) has been associated with increased risks of several cancers. In this study, we used a large case control study to evaluate the association of overall telomere length in PBLs with the risk of lung cancer.
Methods: We measured the overall telomere lengths in PBLs using real-time quantitative PCR method in a large case-control study with 769 Caucasian lung cancer cases and 769 age, gender, and ethnicity matched healthy controls Wilcoxon rank sum test was used to compare the differences between case patients and control subjects. Unconditional multivariate logistic regression analysis was used to assess the association between telomere length and lung cancer risk. In addition, the effect of age, gender and smoking status was evaluated and correlation analyses between variables were performed.
Results: As expected, telomere length was inversely correlated with age in both cases and controls. Lung cancer patients had significantly shorter overall telomere lengths (mean ± standard deviation: 1.20 ±0.37 versus 1.25 ±0.35 p =0.002) than controls, which was only evident in men (1.15 ±0.36 versus 1.24 ±0.36 p &lt;0.001) but not in women. Multivariate logistic regression analysis showed that short overall telomere length was associated with a dose-dependent increase in lung cancer risk. Compared to the individuals within the highest quartile of telomere length, the OR for those within the 3rd, 2nd and 1st quartiles was 0.88 (95% CI 0.65-1.18), 1.08 (95% CI 0.80-1.44) and 1.49 (95% CI 1.12-1.99), respectively (p for trend &lt; 0.001). This effect was more pronounced in current and former smokers (p for trend &lt; 0.001) than in nonsmokers. There was a significant interaction between smoking and overall telomere length in elevating lung cancer risk (p for interaction &lt;0.001).
Conclusions: This is the largest epidemiological study to evaluate constitutive telomere length and lung cancer risk. Our data strongly support the role of telomere dysfunction in lung carcinogenesis, highlighting its specific interaction with smoking.
Citation Format: Beatriz Sanchez-Espiridion, Jian Gu, David W. Chang, Joe Y. Chang, Charles Lu, Jack A. Roth, Xifeng Wu. Constitutive short telomere length and lung cancer risk: a large case- control study. [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 2554. doi:10.1158/1538-7445.AM2013-2554
Abstract 2557: Genetic variants in microRNA genes and breast cancer risk.
Authors: Beeghly-Fadiel Alicia C. , Sung Hyuna , Zhang Ben , Choi Ji-Yeob , Delahanty Ryan J. , Long Jirong , Gao Yu-Tang , Lu Wei , Cai Qiuyin , Shu Xiao Ou , King Daehee , Zheng Wei 
Published: August 2014

Abstract
microRNA (miRNA) are small noncoding molecules that function as regulators of the genome. Genetic variants in miRNA binding sites and miRNA genes have begun to be evaluated in relation to disease risk; however, no studies have yet comprehensively evaluated miRNA variants in relation to breast cancer risk. Using a two stage study design, and genome-wide association study (GWAS) data, we evaluated genetic variants within 1,425 miRNA genes (±5kb). In Stage 1, a total of 2,213 common genetic variants were evaluated among 2,876 breast cancer cases and 2,285 controls using data from the Shanghai Breast Cancer Genetics Study. Nominally significant associations (P value ≤0.05) were found for 108 variants in 96 genetic loci (r²≥0.6). In Stage 2, 94 variants in 84 loci were evaluated among 2,225 cases and 2,052 controls from the Seoul Breast Cancer Study; nine variants in eight loci had nominally significant associations. In analyses of the two study stages combined, 14 loci had highly significant associations (P value ≤0.01) and 19 additional loci had significant associations (P value ≤0.05) with breast cancer risk, all with consistent directions of association between the two study stages. These 36 variants in 33 loci have been mapped to 16 miRNA genes, many in the promoter regions. Based on our findings, genetic variants in miRNA genes are likely to contribute to breast cancer susceptibility.
Citation Format: Alicia C. Beeghly-Fadiel, Hyuna Sung, Ben Zhang, Ji-Yeob Choi, Ryan J. Delahanty, Jirong Long, Yu-Tang Gao, Wei Lu, Qiuyin Cai, Xiao Ou Shu, Daehee King, Wei Zheng. Genetic variants in microRNA genes and breast cancer risk. [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 2557. doi:10.1158/1538-7445.AM2013-2557
Abstract 256: Elucidating the role of ARID3B in ovarian cancer stem cells.
Authors: Deneke Victoria E. , Roy Lynn , Dahl Richard , Cowden Dahl Karen D. 
Published: August 2014

Abstract
Ovarian cancer is the fifth leading cause of cancer death among US women and accounts for more deaths than any other cancer of gynecological origin. In light of the lethality, it is critical to discover and understand the common molecular characteristics in ovarian cancer. Our lab demonstrated that ARID3B, a member of the AT-rich interactive domain family of proteins, is overexpressed in ovarian cancer. Furthermore, ARID3B is essential for embryonic development and is present in embryonic stem cells. Overexpression of ARID3B in ovarian cancer cells leads to increased tumor growth and decreased survival in xenograft studies. Therefore, we hypothesize that ARID3B regulates cancer stem cell production, which enhances tumorigenesis. We have found that stem-cell marker CD133 is upregulated in ovarian cancer human cell line SKOV3IP overexpressing ARID3B. We are currently assessing the mechanism for ARID3B regulation of ovarian cancer stem cells using in vitro models. Determining the role of ARID3B in cancer stem cells may help us better understand the molecular mechanisms that regulate tumor initiation, chemoresistance, and ovarian cancer progression.
Citation Format: Victoria E. Deneke, Lynn Roy, Richard Dahl, Karen D. Cowden Dahl. Elucidating the role of ARID3B in ovarian cancer stem 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 256. doi:10.1158/1538-7445.AM2013-256
Abstract 2563: Identification and functional characterization of a novel UGT2A1 splice variant: Potential importance in tobacco-related cancer susceptibility .
Authors: Bushey Ryan T. , Chen Gang , Lazarus Philip 
Published: August 2014

Abstract
UGT2A1 is a phase II enzyme highly expressed in the respiratory and aerodigestive tracts. In the present study, a novel exon 3 deletion splice variant for UGT2A1 (termed ‘UGT2A1Δexon3’) was characterized. As determined by reverse-transcription polymerase chain reaction, UGT2A1Δexon3 was shown to be co-expressed with wild-type UGT2A1 in various tissues including lung, trachea, larynx, tonsil, and colon. The mRNA expression ratio of UGT2A1Δexon3:wild-type UGT2A1 was highest in colon (0.79±0.08) and lung (0.42±0.12) as determined by real-time PCR; splice variant protein (termed ‘UGT2A1_i2’) to wild-type protein (termed ‘UGT2A1_i1’) ratios were in the range of 0.5-0.9 in these tissues as determined by Western blot analysis using an UGT2A1-specific antibody. In contrast to the UGT2A1 wild-type isoform, homogenates prepared from UGT2A1_i2-over-expressing HEK293 cells exhibited no glucuronidation activity against PAHs, including benzo(a)pyrene-7,8-dihydrodiol (B(a)P-7,8-diol). An inducible in vitro system was created to determine the effect of UGT2A1_i2 expression on UGT2A1_i1 activity. Increasing UGT2A1_i2 levels resulted in a significant (p&lt;0.01) decrease in the UGT2A1_i1 Vmax against 1-hydroxy (OH)-pyrene, 3-OH-B(a)P and B(a)P-7,8-diol; no significant changes in KM were observed for any of the three substrates. Co-immunoprecipitation experiments suggested the formation of UGT2A1_i1 and UGT2A1_i2 hetero-oligomers and UGT2A1_i1 homo-oligomers; co-expression of UGT2A1_i1 or UGT2A1_i2 with other UGT1A or UGT2B enzymes caused no change in UGT1A or UGT2B glucuronidation activity. These data suggest that a novel UGT2A1 splice variant regulates UGT2A1-mediated glucuronidation activity via UGT2A1-specific protein-protein interactions, and that expression of this variant could play an important role in the detoxification of carcinogens within target tissues for tobacco carcinogenesis.
Citation Format: Ryan T. Bushey, Gang Chen, Philip Lazarus. Identification and functional characterization of a novel UGT2A1 splice variant: Potential importance in tobacco-related cancer susceptibility . [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 2563. doi:10.1158/1538-7445.AM2013-2563
Abstract 2568: Genetic association of POU5F1B at 8q24 with prostate cancer.
Authors: Breyer Joan P. , Smith Jeffrey R. 
Published: August 2014

Abstract
Numerous genetic variants at 8q24 have been associated with risk for multiple common cancers, most prominently for prostate cancer. POU5F1B is a retrotransposed copy of the master stem cell factor OCT4, and one of few known genes within the 8q24 interval. While OCT4 is expressed selectively in embryonic stem cells, POU5F1B retains its open reading frame and has been shown to be expressed in cancers. Ectopic expression of OCT4 blocks progenitor cell differentiation and causes dysplasia, raising the possibility that aberrant expression of POU5F1B might have analogous effects. Because POU5F1B sequence is non-unique, a potential contribution of POU5F1B genetic variation to cancer risk has not been investigated in prior GWAS. We evaluated genetic variants of POU5F1B for association with prostate cancer within a case-control study of familial prostate cancer at Vanderbilt University that included 830 familial prostate cancer probands, and 830 age-matched control probands without a personal or family history of prostate cancer. Our study identified four missense variants within POU5F1B, and eight haplotypes of &gt; 1% frequency. G176E was associated with prostate cancer (P = 3.1 x 10−4) and was in LD with GWAS SNP rs6983267 (r2 = 0.69). The minor allele (encoding glutamate) uniquely marked a single haplotype (the most common) with an inverse association with prostate cancer (P = 5.7 x 10−4, OR = 0.78 (95%CI 0.7-0.9)). As expected, the haplotype association was correlated with that of GWAS SNP rs6983267. A second haplotype differing from the first only at G176E (encoding glycine) was independently associated with risk of prostate cancer (P = 5.5 x 10−7, OR = 1.91 (95%CI 1.5-2.5)). However, glycine would also be encoded at this position by all other haplotypes, none carrying a risk effect. The risk haplotype was tagged by the pair of missense variants, G176E (glycine) and E238Q (glutamine). In a single allele analysis, the latter variant had no apparent association with prostate cancer. The risk effect of the former adjusted for the latter was OR = 2.12 (95%CI 1.6-2.7), P = 1.7 x 10−8; the risk effect of the latter adjusted for the former was OR = 1.79 (95%CI 1.4-2.3), P = 9.4 x 10−6. The two missense variants would alter each of the DNA-binding domains: one altering a highly conserved site with a non-conservative substitution, and the other abrogating a kinase site known to physiologically regulate other POU transcription factors. Our data suggest that combinations of these variants may be associated with risk of prostate cancer and warrant further investigation of the potential role of POU5F1B in the 8q24 cancer associations.
Citation Format: Joan P. Breyer, Jeffrey R. Smith. Genetic association of POU5F1B at 8q24 with prostate 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 2568. doi:10.1158/1538-7445.AM2013-2568
Abstract 258: Growth factor signaling is critical in the maintenance of cancer stem cell population in head and neck squamous cell cancer.
Authors: Leong Hui Sun , Sew Pui Hoon , Chong Fui Teen , Tan Daniel Shao-Weng , Iyer Narayanan Gopalakrishna 
Published: August 2014

Abstract
Tumor heterogeneity is an important concept in the carcinogenesis of solid tumors, and forms the background for the cancer-stem cell (CSCs) hypothesis. Emerging data suggests however that there is plasticity within various cancer sub-populations, and that CSCs exists in a contextually regulated equilibrium, which is multi-directional and less rigid than previously hypothesized. The aim of this study was to establish an in vitro system that recapitulates stem cell plasticity in head and neck squamous cell cancers (HNSCC), and identify factors that play a role in the maintenance and re-population of CSCs.
Tumor spheres were established using patient-derived tumor cells via anchorage-independent cell culture techniques. RT-PCR showed higher expression of KLF4, SOX2 and Nanog in tumor spheres compared to monolayer culture cells. Cells grown as tumor spheres were more resistant to γ-radiation, 5-fluorouracil, cisplatin and etoposide treatment compared to cells grown in monolayer culture. Using the ALDEFLUOR assays to identify CSCs, we showed that more cells in tumor spheres had high aldehyde dehydrogenase (ALD+ cells) activity. Monolayer cultures were subject to single cell cloning to generate clones with high and low ALD+ fractions. As expected, ALDHigh clones showed higher expression of stem cell markers Oct4, Bmi1 and Nanog and EMT markers N-Cadherin, Slug, Snail, β-Catenin, Vimentin compared to ALDLow clones. When ALDHigh clones from HNSCC cells were cultured over time, ALD+ fractions were found to reduce gradually and equilibrate at a specified ALD+ fraction specific to each cell line grown in regular culture media. When growth factors EGF and/or insulin were added to the media, ALD+ fractions could be maintained at higher levels as compared to baseline. ALDHigh clones also showed increased EGFR and IGF-1R phosphorylation when grown in regular culture conditions, with increased activation of downstream factors involving the AKT and ERK pathways compared with ALDLow clones. Blocking these pathways using specific inhibitors against EGFR and IGFR reduced stem cell fractions drastically.
Taken together, these results show that HNSCC CSCs exhibit plasticity, where the maintenance of the stem cell fraction was dependent on the EGF and IGF pathways, which are therefore vulnerable to therapeutic targeting.
Citation Format: Hui Sun Leong, Pui Hoon Sew, Fui Teen Chong, Daniel Shao-Weng Tan, Narayanan Gopalakrishna Iyer. Growth factor signaling is critical in the maintenance of cancer stem cell population in head and neck squamous cell 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 258. doi:10.1158/1538-7445.AM2013-258
Abstract 2589: The P110 subunit of PI3-K is a therapeutic target of acacetin in skin cancer.
Authors: Kim Jon Eun , Jung Sung Keun , Byun Sanguine , Lee Sung-Young , Kim Myoung Ok , Lim Tae Gyu , Bode Ann M. , Lee Hyong Joo , Lee Ki Won , Dong Zigang 
Published: August 2014

Abstract
Verifying potential target proteins of phytochemicals is important for explaining their health benefits. In the present study, we examined the chemopreventive effect and molecular target of acacetin, which is a flavonoid from Robinia Psuedoacacia also known as Black Locust. Treatment with acacetin significantly inhibits EGF-induced transformation of JB6 P+ cells. Western blot assay results revealed that acacetin suppresses EGF-induced phosphorylation of Akt/p70S6K, which is a well-known downstream signaling molecule of phosphatidylinositol 3-kinase (PI3-K). In vitro kinase and pull-down assay results showed that acacetin significantly inhibits PI3-K activity by direct binding. Additionally, acacetin also attenuated EGF-induced PI3-K activity and binds with PI3-K in JB6 P+ cells. Acacetin showed significant effects against anchorage-dependent and -independent cell growth in cells displaying higher PI3-K activity compared with those exhibiting lower PI3-K activity. Binding assay data and computational modeling showed that acacetin binds in an ATP-competitive manner with the p110 kinase domain of PI3-K and interacts with Val828, Glu826 Asp911 Trp760, Ile777, Ile825, Tyr813, Ile910 and Met900. Acacetin reduced SK-MEL-28 xenograft tumor growth and phosphorylation of Akt in vivo. Overall, these results indicate that acacetin is an ATP competitive PI3-K inhibitor and might be a promising chemopreventive agent targeting PI3-K activity.
Citation Format: Jon Eun Kim, Sung Keun Jung, Sanguine Byun, Sung-Young Lee, Myoung Ok Kim, Tae Gyu Lim, Ann M. Bode, Hyong Joo Lee, Ki Won Lee, Zigang Dong. The P110 subunit of PI3-K is a therapeutic target of acacetin in skin 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 2589. doi:10.1158/1538-7445.AM2013-2589
Abstract 259: Novel biliary tract cancer stem cell biomarker TAGLN2 regulates migration via c-met signaling cascades in biliary tract cancer cells.
Authors: Park Soo Been , Kim Sun A , Song Si Young 
Published: August 2014

Abstract
Background/Aims : Biliary tract cancer is one of the lethal malignancy. Most biliary tract cancer is diagnosed at advanced stages and have poor prognosis. Currently, there are no standard biomarkers and chemotherapeutic agents for biliary tract cancers. In order to find the biomarkers and therapeutic targets for biliary tract cancer, we have focused on the cancer stem cells (CSCs) with tumor initiating/self renewing/metastatic capacity and chemo/radio-resistance. In this study, we investigated the function of biliary tract CSC related biomarker TALGN2 discovered from comparision of cDNA microarray between sphere and adherent cell populations of biliary tract cancer cell lines.
Methods : Analysis using cDNA microarray between sphere and adherent cell populations and selection of CSC specific biomarkers were performed. Among them, we selected TAGLN2 as a biliary CSC related gene. TAGLN2 expression was confirmed by RT-PCR, western blot and immunohistochemistry. To evaluate the function of TAGLN2 in biliary carcinogenesis, we performed targeted knockdown via siRNA in SNU1196 biliary tract cancer cell line.
Results : The expression of stemness and c-met signaling cascades were up-regulated in sphere cells compared with adherent cells. TAGLN2 was also up-regulated in sphere cells. TAGLN2 was highly expressed in most of biliary tract cancer cell lines and biliary tract cancer tissues. TAGLN2 knockdown cells showed decreased cell migration and increased chemosentitivity compared with mock cells. In addition, we found that c-met signaling cascades including PI3K and MAPK were inactivated in TAGLN2 knockdown cells.
Conclusions : These results suggest that biliary tract CSC biomarker TAGLN2 is implicated in biliary tract cancer progression and TAGLN2 may be a potential biomarker and therapeutic target for biliary tract cancer.
Citation Format: Soo Been Park, Sun A Kim, Si Young Song. Novel biliary tract cancer stem cell biomarker TAGLN2 regulates migration via c-met signaling cascades in biliary tract 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 259. doi:10.1158/1538-7445.AM2013-259
Abstract 261: Podocalyxin-like 1 promotes stemness and metastasis of cancer cells through activating cortactin.
Authors: Lin Cheng-Wei , Sun Min-Shiou , Liao Mei-Ying , Yu John , Chiou Li-Ting , Wu Han-Chung 
Published: August 2014

Abstract
Cancer stem cells (CSCs) are involved in tumor-initiation, self-renewal, and metastasis. CSCs share many similar biological properties with embryonic stem cells (ESCs). Currently, there still lacks a biomarker that can specifically identify CSCs. Therefore, the signaling mechanism underlying the metastatic process due to CSCs is still unclear. In the present study, we used hybridoma to identify cell surface biomarker that was coexpressed on both ESCs and cancer cells. We found that podocalyxin-like 1 (PODXL) was expressed abundantly on both ESCs and cancer cells. The expression of PODXL, which was upregulated in tumorsphere, was found to be associated with CSCs markers. Additionally, overexpression of PODXL was correlated with lymph node metastasis and cancer malignancy. Knockdown of PODXL suppressed tumor self-renewal, invasiveness, and metastasis. Further study of its molecular mechanism revealed that PODXL induces focal adhesion kinase activation, F-actin polymerization, and invadopodia formation by interacting with and activating cortactin. Collectively, we found that PODXL promotes tumor self-renewal and initiation and that the elevation of PODXL enhances local tumor cells invasiveness and distant organ metastasis. Therefore, PODXL might be a biomarker for CSC and a potential target for the development of CSC therapeutics.
Citation Format: Cheng-Wei Lin, Min-Shiou Sun, Mei-Ying Liao, John Yu, Li-Ting Chiou, Han-Chung Wu. Podocalyxin-like 1 promotes stemness and metastasis of cancer cells through activating cortactin. [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 261. doi:10.1158/1538-7445.AM2013-261