bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1659: Evaluation of microRNA expression profiles and their associations with risk alleles in lymphoblastoid cell lines of familial ovarian cancer
Authors: Shen Jie , Wang Dan , Gregory Steven , Medico Leo , Hu Qiang , Lele Shashikant , Odunsi Kunle , Ambrosone Christine , Liu Song , Zhao Hua 
Published: August 2012

Abstract
Interindividual variations of microRNA expression are likely to influence the expression of microRNA target genes, and therefore, contribute to phenotypic differences in humans, including cancer susceptibility. Whether microRNA expression variation has any role in ovarian cancer development is still unknown. Here we evaluated microRNA expression profiles in lymphoblastoid cell lines (LCLs) from 74 women with familial ovarian cancer and 47 controls. We found that microRNA expression profiles in the LCLs of the cases were significantly different from that in the controls with 91% accuracy by 95 differentially expressed microRNAs. To assess the potential implications of microRNAs in ovarian cancer, we investigated the associations between microRNA expression and ovarian cancer risk alleles discovered from genome wide association studies. We observed 130 significant associations at a permutation level of 0.01. Compared to other risk variants, rs3814113 and rs2072590 had the greatest number of significant associations (68 and 37, respectively). Interestingly, 14 microRNAs which were associated with ovarian cancer risk alleles belong to 5 microRNA clusters. The most notable cluster is the tumorigenic miR-17-92 cluster with 5 microRNAs, all of which are significantly associated with rs3814113. Using pathway analysis, several key biological pathways were significantly overrepresented, such as cellular response to stress (P=2.87x10−06), etc. Our results indicate that microRNA expression profiles in LCLs can serve as potential detection biomarkers for familial ovarian cancer. Further characterization of significant associations between microRNAs and risk alleles could facilitate the understanding of the functions of these GWAS discovered risk alleles in the genetic etiology of ovarian cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1659. doi:1538-7445.AM2012-1659
Abstract 166: A novel therapeutic approach for triple negative breast cancer
Authors: Boopalan Thiyagarajan , Arumugam Arunkumar , Suman Suman , Das Trinath P. , Damodaran Chendil , Lakshmanaswamy Rajkumar 
Published: August 2012

Abstract
Triple negative breast cancers (TNBCs) are defined as tumors that lack expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (EGFR2). TNBCs account for 15-20% of all breast tumors. These breast tumors are usually aggressive and have a specific molecular profile. Unfortunately, treatment options for TNBCs are limited, leading to a poor prognosis and high mortality rates. Thus, novel therapeutic approaches are needed to treat TNBCs. To date, several molecular targets have been identified (e.g., PARP, EGFR, mTOR, Akt, and BRAC-1). Moreover, many pre-clinical and clinical trials are underway to determine the efficacy of specific inhibitors against these molecular targets, used either alone or in combination with chemotherapeutic agents. So far, these trials have failed to produce significant promising results. Hence, our goal is to identify novel therapeutic agents that specifically target breast tumor cells, especially TNBCs, without causing toxicity to normal cells. Our studies identified nimbolide as a novel therapeutic agent. Nimbolide is a major bioactive compound derived from the Azadirachta indica (Neem) leaves, which is well-known medicinal plant having a wide spectrum of biological activities. In our studies, nimbolide targeted TNBC cells without causing toxicity to normal primary breast epithelial cells. We also explored the molecular mechanism underlying the anti-cancer effect of nimbolide on TNBC cells and found that nimbolide, simultaneously inhibited phosphorylation of Akt mediates pro-survival signaling. In addition, downstream signaling by mTOR and NF-kappa-B was down regulated by nimbolide which resulted in the induction of pJNK and pc-Jun mediated pro-apoptotic signaling and apoptosis in TNBC cells. These changes in the pro and anti-apoptotic molecular circuits also inhibited migration and invasion properties of TNBC cells. Altogether, our results strongly suggest that nimbolide could be a potent compound for the prevention and/or treatment of TNBC. Our ongoing in vivo studies may reveal the in vivo efficacy of nimbolide and toxicity to other organs or cells if any.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 166. doi:1538-7445.AM2012-166
Abstract 1661: Fine-mapping of GWAS variants in BMP4, GREM1, CDH1, and RHPN2 in African American colorectal cancer patients
Authors: Kupfer Sonia , Ludvik Anton E. , Hong Ellie , Hooker Stanley , Kittles Rick , Keku Temitope , Sandler Robert , Ellis Nathan A. 
Published: August 2012

Abstract
Background: Genome-wide association studies (GWAS) of colorectal cancer (CRC) have identified risk variants in candidate genes involved in TGF-ß signaling including BMP4, GREM1, CDH1, RHPN2 and SMAD7. We previously replicated the association with a 3′-UTR SNP in GREM1 (rs10318) in African Americans but did not find evidence of associations in the other genes. This finding could be explained by different genomic structure in African Americans. Therefore, we sought to fine-map these genes to identify CRC risk variants in African Americans who are at highest risk of CRC in the US. Methods: DNA from cases and controls was obtained from two US institutions. In total, we included DNA from 795 AA cases and 985 AA controls. TagSNPs with minor allele frequencies &gt;5% and pairwise r2 &gt;0.8 were identified in five genes using YRI Hapmap data. A total of 81 SNPs were genotyped in cases and controls using Sequenom MassARRAY. We calculated odds ratios and 95% confidence intervals using logistic regression controlling for ancestry, age, gender and multiple testing in PLINK. Results: Association analysis was completed for four genes: BMP4, GREM1, CDH1 and RHPN2. The top tagSNP associations for each gene are shown in the Table. None of the SNPs were significant after permutation testing. In GREM1, the strongest SNP associations were found at the 3′ end of the gene. In BMP4, we identified two SNPs (rs1957852 and rs7146040) that are in LD with rs4444235 previously identified in a European GWAS. In CDH1, rs12931189 is located in the same LD block as the strongest association signal (rs7199991) in a recent fine-mapping study in Europeans. Finally, we have no evidence for associations in RHPN2 in African Americans. Conclusion: These results provide preliminary evidence of associations in African American colorectal cancer patients in BMP4, GREM1 and CDH1 identified by GWAS in Europeans. Ongoing work is testing associations in SMAD7 and further fine-mapping by imputation and resequencing in these regions.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1661. doi:1538-7445.AM2012-1661
Abstract 1665: High resolution genome profile in familial colorectal cases without mutations on mismatch repair genes
Authors: Villacis Rolando AR , Abreu Francine B. , Santos Érika MM , Rossi Benedito M. , Carraro Dirce M. , Kowalski Luiz P. , Rogatto Silvia R. 
Published: August 2012

Abstract
Colorectal cancer (CRC) represents the fourth leading cause of cancer mortality. Approximately 30% of all CRC cases have a hereditary component, but only 5% are associated with inherited mutations in known genes. The most common hereditary syndrome of CRC is the Lynch syndrome (LS) and is caused by mutations in mismatch repair genes, mainly MLH1 and MSH2. In ∼50% of families classified with the Amsterdam criteria not show germline mutations in mismatch repair genes, suggesting that other genetic factors are associated with predisposition to CRC. In this study, it was evaluated germline copy number alterations (CNAs) in 57 LS patients without pathogenic mutations in mismatch repair genes (MLH1, MSH2, MSH6, PMS1 and PMS2), as well as in CHEK2 and TP53, by array comparative genomic hybridization (aCGH) using a platform of 4x180K (Agilent). Genomic data were extracted with Feature Extraction software and analyzed using Nexus 6.0 software, statistical algorithm FASST2 Segmentation and sensitivity threshold of 5.0E-6. The aCGH data showed a total of 361 CNAs (in average, 6.3±3.8 CNA/individual) including 144 gains and 217 genomic losses. After the comparison with a reference dataset obtained from 100 healthy Brazilian individuals (Krepischi et al, 2011; personal communication) and exclusion of the CNAs detected in more than 5% of this reference dataset, it was identified ∼100 rare CNAs. Most of them were detected in only one case, however, six CNAs were common at least in five cases: 1p11.2, 1p36.32, 7p22.3, 8q24.3, 9p11.2 and 18q11.1. The ROCK1 gene, mapped on 18q11.1, was found as involved in nine cases (three losses and six gains). This gene was associated with carcinogenesis and progression of human tumors, including colon cancer (Nakashima et al, Int J Oncol. 36:585, 2010). Amplification on 7p22.3 (5 cases), where is mapped the homeobox gene UNCX, a transcription factor involved in somitogenesis and neurogenesis. Mutations in rare constitutional CNAs may affect genes or major pathways associated with cancer, offering an explanation for families with high cancer risk. In CRC, the large scale analysis of germline CNAs in patients and their relatives can allow the identification of new genes involved in tumor predisposition. Financial support: FAPESP and CNPq
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1665. doi:1538-7445.AM2012-1665
Abstract 1666: Mitochondrial DNA sequence mutations and risk of pancreatic cancer
Authors: Tranah Gregory J. , Lam Ernest T. , Bracci Paige M. , Holly Elizabeth A. 
Published: August 2012

Abstract
Although the mitochondrial genome exhibits high mutation rates, common mitochondrial DNA (mtDNA) variation has not been consistently associated with pancreatic cancer. Here, we comprehensively examined mitochondrial genomic variation by sequencing the mtDNA of participants (cases=286, controls=283) in a San Francisco Bay Area pancreatic cancer case-control study. Five common variants were associated with pancreatic cancer at nominal statistical significance (p&lt;0.05) with the strongest finding for mt5460g in the ND2 gene (odds ratio (OR)=3.9, 95% confidence interval (CI)=1.5-10; p=0.004) which encodes an A331T substitution. Haplogroup K was nominally associated with reduced pancreatic cancer risk (OR = 0.32, CI=0.13-0.76; p=0.01) when compared with the most common haplogroup, H. A total of 19 haplogroup-specific rare variants yielded nominal statistically significant associations (p&lt;0.05) with pancreatic cancer risk, with the majority observed in genes involved in oxidative phosphorylation. Weighted-sum statistics were used to identify an aggregate effect of variants in the 22 mitochondrial tRNAs on pancreatic cancer risk (p=0.02). While the burden of singleton variants in the HV2 and 12S RNA regions was three times higher among European haplogroup N cases than controls, the prevalence of singleton variants in ND4 and ND5 was two to three times higher among African haplogroup L cases than in controls. Together, the results of this study provide evidence that aggregated common and rare variants and the accumulation of singleton variants are important contributors to pancreatic cancer risk.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1666. doi:1538-7445.AM2012-1666
Abstract 167: Myricetin suppresses UVB-induced photoaging, skin cancer, and angiogenesis by targeting multiple kinases
Authors: Jung Sung Keun , Lee Ki Won , Bode Ann M. , Lee Hyong Joo , Dong Zigang 
Published: August 2012

Abstract
Chronic exposure to solar ultraviolet is a major cause of photoaging and skin carcinogenesis. In the present study, we investigated the effect of myricetin on UVB-induced photoaging, skin cancer, and angiogenesis in JB6 P+ cells and a mouse skin tumorigenesis model. Myricetin inhibited wrinkle formation induced by UVB irradiation (0.18 J/cm2, 3 days/week for 15 weeks) in mouse skin. Myricetin treatment reduced UVB-induced epidermal thickening of mouse skin and also suppressed UVB-induced matrix metalloproteinase-9 (MMP-9) protein expression and enzyme activity. In vitro and in vivo pull-down and kinase assays revealed that myricetin suppressed Raf activity by binding with Raf. Secondly, myricetin suppressed UVB-induced COX-2 expression and mitogen-activated protein kinases in JB6 P+ cells and mouse skin. Pull-down and kinase assay results showed that myricetin directly inhibited UVB-induced Fyn kinase activity by binding with Fyn in an ATP-competitive manner. Mouse skin tumorigenesis data clearly showed that pretreatment with myricetin significantly suppressed UVB-induced skin tumor incidence in a dose-dependent manner. Topical treatment with myricetin suppressed repetitive UVB-induced neovascularization in the SKH-1 hairless mouse skin. The induction of vascular endothelial growth factor, matrix metalloproteinase (MMP)-9 and MMP-13 expression by chronic UVB irradiation was substantially suppressed by myricetin treatment. Immunohistochemical and Western blot analyses revealed that myricetin attenuated UVB-induced hypoxia inducible factor-1alpha expression in mouse skin. In vivo kinase and pull down assay data revealed that myricetin suppressed UVB-induced phosphatidylinositol 3 (PI3)-kinase activity by direct binding with PI3-kinase. Overall, together these results suggest that the anti-photoaging, anti-skin carcinogenesis, and anti-angiogenesis effects of myricetin are due to mainly targeting Raf, Fyn, and PI3-K, respectively.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 167. doi:1538-7445.AM2012-167
Abstract 1674: Two phase study of KCNJ1 polymorphisms, calcium, magnesium and colorectal adenoma risk, results from the Tennessee Colorectal Polyp Study
Authors: Zhu Xiangzhu , Shrubsole Martha J. , Ness Reid M. , Cai Qiuyin , Long Jirong , Chen Zhi , Deng Xinqing , Smalley Walter E. , Edwards Todd , Zheng Wei , Dai Qi 
Published: August 2012

Abstract
Background: Previous studies generated inconsistent results on the associations between intakes of calcium and magnesium with risk of colorectal adenoma and cancer. It is possible that some of the inconsistency is due to a modifying effect by genetic polymorphisms involved in calcium and magnesium homeostasis. The KCNJ1 gene encodes the Inward-rectifier potassium channel (ROMK). ROMK plays an essential role in the homeostasis of potassium, which is critical for the reabsorption of calcium and magnesium. Objectives: We hypothesize that common variants in KCNJ1 may modify the associations between intakes of calcium and/or magnesium and risk of colorectal adenoma risk. Methods: Included were participants of the Tennessee Colorectal Polyp Study (TCPS), a colonoscopy-based case control study conducted in Nashville, TN. In the phase I study, genotyping was performed using the Affymetrix Human Mapping 500K array set in 958 colorectal adenoma cases and 909 controls and 13 tagging single-nucleotide polymorphisms (SNPs) in the KCNJ1 gene were evaluated. SNPs identified as significant in phase I were genotyped in phase II in an independent set (860 cases and 3083 controls). Results: In phase I, 1 tagging SNP was significantly associated with adenoma risk and 8 SNPs were interacted significantly with calcium or magnesium intake in risk of colorectal adenoma. In phase II, only 1 of the 9 SNPs significantly interacted with calcium and magnesium intakes in relation to colorectal adenoma although the genotype per se was not directly associated with the risk. In combined analysis, the p value for the interaction between the SNP and calcium intake was 0.00015 and it remained statistically significant after Bonferroni correction for multiple comparisons. In stratified analyses by levels of calcium and magnesium (above or below RDA levels), we found adenoma risk significantly increased for those who with at least 1 variant allele and whose intake levels of calcium and magnesium were below the RDA levels, with ORs (95% CI) of 1.35 (1.10, 1.67) and 1.43 (1.08, 1.89) respectively, compared to those who did not possess the variant allele. The corresponding ORs (95% CI) increased to 1.84 (1.33, 2.53) and 2.30 (1.53, 3.46), respectively, multiple adenomas versus controls. Conclusions: In this two-stage analysis, we found no overall association of adenoma with KCNJ1 genotype. However, common KCNJ1 variants significantly interacted with intakes of calcium and magnesium in risk of colorectal adenoma, particular for multiple adenomas.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1674. doi:1538-7445.AM2012-1674
Abstract 1681: Genetic ancestry distribution in basal-cell carcinoma cases and controls from Puerto Rico
Authors: Diaz-Zabala Hector , Dutil Julie , Matta Jaime 
Published: August 2012

Abstract
Introduction: The incidence and clinical presentation of Basal-cell carcinoma (BCC) vary among different ethnic subgroups. In the Hispanic population of Puerto Rico, the contribution of genetic ancestral factors in determining BCC risk and its clinical presentation is unknown. Methods: The study population consists of 83 BCC skin cancer cases and 89 controls recruited from a private dermatology practice in Ponce, Puerto Rico. A panel of 106 ancestry informative markers was genotyped using iPLEX Sequenom technology. Individual genetic ancestry was estimated using a maximum likelihood approach. The distribution of genetic ancestry was compared between cases and controls. Results: The distribution of genetic ancestry among the 172 study subjects varied from 0 to 89% African, 11 to 99% European, and 0 to 70% Native American. There was no significant difference in the average European (p= 0.891), African (p= 0.44) and Native American (p= 0.232) ancestry proportions between BCC cases and controls. Conclusions: Global genetic ancestry does not seem to contribute significantly to the risk of BCC in the Puerto Rican population.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1681. doi:1538-7445.AM2012-1681
Abstract 1683: ALK F1174L kinase activity as driver of cell proliferation in neuroblastoma cell line models and neuroblastoma tumors
Authors: Hilhorst Riet , Hovestad Liesbeth , de Wijn Rik , Pijnenburg Dirk , Ruijtenbeek Rob , Schramm Alexander , Eggert Angelika , Schulte Johannes H. 
Published: August 2012

Abstract
Background. Whereas ALK translocations play a role in tumor growth in selected NSCLC cases, mutated forms of ALK have been shown to drive development of neuroblastoma, the most common malignant extracranial tumor of childhood. The mutation F1147L in the oncogene ALK increases the kinase activity, causing deregulated proliferation of sympatho-adrenal progenitor cells. We explored the use of kinase activity measurements to identify ALK activity in cell lysates and patient derived tissue lysates with the aim of identifying biomarkers to trace the activity of ALK in tumors and the effect of ALK inhibitors on these marker signals. Methods. Protein kinase activities were measured on PamChip® peptide microarrays comprising 144 Tyr containing peptide sequences from known human phosphorylation sites. The activity profiling experiments involved recombinant ALK kinase, lysates of cell lines overexpressing ALK and neuroblastoma tumors with elevated ALK F1174L presence. Per microarray analysis 5 ug of total protein was used in the presence of 100 uM ATP. Experiments were performed in the presence and absence of ALK kinase inhibitors crizotinib and NVP-TAE684. Real time kinetics of 144 peptide phosphorylations were measured with a fluorescently labeled antibody. Results. Phosphorylation profiles for neuroblastoma tumors, ALK overexpressing cell lines and recALK were generated. For recALK 48 novel peptide substrates were identified that showed signals depending on both ATP and kinase concentration and inhibition by the ALK inhibitors. In ALK overexpressing cell lines, but not in control cell lysates, signals on many ALK substrate peptides were significantly elevated, and returned to baseline level in the presence of ALK inhibitors. Whereas neuroblastomas with low ALK expression gave similar kinase activity profiles, the tumors harboring the ALK F1174L mutation were different, suggesting a more complex regulation of phosphorylation activity in these tumors. All tumors showed on-chip responses with ALK inhibitor drugs, but to different extent, which could be a basis for response prediction biomarker discovery. Conclusion. ALK activity of recombinant kinases, cell lysates and tumor lysates can be detected on PamChip® peptide microarrays. Based on results with model systems, this method shows promise to identify tumors that express elevated ALK activity and to study response of this class to ALK inhibitors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1683. doi:1538-7445.AM2012-1683