bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 121: Angiogenin and the mmp9-timp2 axis are strongly upregulated in pro-angigoenic dnk-like cells isolated from colorectal cancer patients
Authors: Bruno Antonino , Pelosi Giuseppe , Boni Luigi , Dominioni Lorenzo , Mortara Lorenzo , Noonan Douglas , Albini Adriana 
Published: August 2018

Abstract
Natural Killer (NK) cells are effector lymphocytes involved in tumor immunosurveillance. In solid malignancies, tumor associated (TANK; peripheral blood) and tumor infiltrating (TINK) NK cells have compromised functions. We functionally and molecularly characterize TINK and TANKs from blood and tissue samples of colorectal cancer (CRC) patients, a tumor type where inflammation and angiogenesis have clinical relevance, compared to NK isolated from control and non-oncologic inflammatory bowel disease patients.
NK subset distribution and cytokine profiling were performed by multicolor flow cytometry, using peripheral blood and tissue samples from CRC patients, for surface antigen and cytokine profiling characterization. Conditioned media (CM) from FACS-sorted NKs were used either for secretomic profiling using antibody membrane arrays or in functional in vitro angiogenesis assays.
CRC TINKs/TANKs showed decreased activation marker NKG2D, impaired degranulation activity, a decidual-like NK polarization toward the CD56brightCD16dim/- CD9+CD49+ subset. TINKs and TANKs supernatants induced endothelial cell proliferation, migration, adhesion and formation of capillary-like structures in vitro. It has been reported that dNK release proangiogenic factors and metastasis-associated (MMP-9, TIMP1-2) proteins.
We describe for the first time the expression of angiogenin and MMP2, MMP9, TIMP1 and TIMP2 by CRC derived NK cells. This could be a phenotype relevant to their invasive capabilities and pro-angiogenic function. STAT-3/STAT-5 activation was observed in TANKs, and inhibition of the STAT5 pathway by pimozide, an antipsychotic drug, reduced proangiogenic factor VEGF and angiogenin production and capillary-like structure formation, but did not affect the levels of TIMP-1, TIMP-2 and MMP-9.
Citation Format: Antonino Bruno, Giuseppe Pelosi, Luigi Boni, Lorenzo Dominioni, Lorenzo Mortara, Douglas Noonan, Adriana Albini. Angiogenin and the mmp9-timp2 axis are strongly upregulated in pro-angigoenic dnk-like cells isolated from colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 121.
Abstract 1217: The association between birth order and childhood brain tumors: A systematic review and meta-analysis
Authors: Nguyen Mai V. , Tran Mo Thi , Tran Chi TDu , Tran Quang H. , Tuong Thuy Thi-Van , Le Linh C. , Boffetta Paolo , Luu Hung N. 
Published: August 2018

Abstract
Background: The incidence of childhood brain tumors (CBT) has increased worldwide, likely resulting from the improvements of early diagnostics. The only known risk factors for CBT are the Li-Fraumeni syndrome and iodization. While both genetic and environmental factors are suggested roles in CBT, birth characteristics, including birth order, maternal age, and mode of delivery, might present the interactions between genetic susceptibility and perinatal environmental causes. Birth order has been hypothesized to play an important role in CBT carcinogenesis due to its possible role as proxy for 1) early infection exposure and 2) hormone levels since first pregnancy differs endocrinologically from later pregnancies. We conducted a systematic review and meta-analysis to clarify the association between birth order and CBT.
Methods: We followed established guidelines to systematically search OvidMedline, PubMed, and the Cochrane Library for English-language studies (both case-control and cohort designs) published prior to November 2017. Meta-analysis provided pooled risk estimates and their 95% confidence intervals (CI) for birth order and CBT. Funnel plots were used to identify sources of heterogeneity and publication bias.
Results: We identified 16 case-control studies with a total sample of 32,439 cases and 166,144 controls. Compared to first birth order, the meta-odds ratio (mOR) for second birth order was 1.04 (95% CI 1.01-1.07), and that for third birth order was 0.98 (95% CI: 0.90-1.06). We also identified 3 cohorts comprising a total of 1,208 cases. The meta-hazard ratio (mHR) for second or higher birth order compared to first birth order was 1.00 (95% CI: 0.96-1.05).
Conclusions: We found no overall association between birth order and CBT in both case-control and cohort study designs; the small association observed for second birth order in case-control studies deserves further consideration. Limited statistical power might have hampered the results of the other analyses.
Citation Format: Mai V. Nguyen, Mo Thi Tran, Chi TDu Tran, Quang H. Tran, Thuy Thi-Van Tuong, Linh C. Le, Paolo Boffetta, Hung N. Luu. The association between birth order and childhood brain tumors: A systematic review and meta-analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1217.
Abstract 1225: Rare variants in DNA damage repair genes are associated with male breast cancer predisposition
Authors: Maguire Sarah L. , Tomczyk Katarzyna , Perrakis Eleni , Saunders Edward , Leongamornlert Daniel , Kote-Jarai ZSofia , Eeles Rosalind , Garcia-Closas Montserrat , Pharoah Paul , Easton Douglas , Lord Christopher J. , Ashworth Alan , Swerdlow Anthony , Orr Nick 
Published: August 2018

Abstract
Male breast cancer accounts for approximately 1% of all breast cancers diagnosed each year in the UK. Germline mutations in DNA damage response genes are known to be associated with many forms of cancer, including breast cancer. In order to identify low frequency male breast cancer predisposition genes, we performed targeted resequencing of more than 300 genes that were selected on the basis of involvement in DNA maintenance and repair pathways. Using a cost-effective protocol based on an automated library preparation method and a multiplexed hybridization enrichment step, we sequenced 1,029 male breast cancer cases from the UK Breast Cancer Now male breast cancer study (MBCS) and 1,254 controls from the MBCS and the ICR1000 UK exome series. Rare variants localising to 19 genes were significantly associated with risk of male breast cancer. Genes with an excess of rare coding mutations included the known breast cancer susceptibility genes BRCA2, CHEK2 and ATM as well as multiple members of the Fanconi anaemia (FA) pathway. Loss of heterozygosity (LOH) affecting the wildtype allele of putative predisposition genes was observed more than 10% of cases with matched tumor samples. In addition to LOH in BRCA2 mutation carries, somatic losses were observed that affected CCNE1, ATM, PALB2, BARD1, CHEK2, POLL and RAD9A. These data represent the largest analysis of rare variants in male breast cancer to date and have enabled the identification of known and putative novel susceptibility genes.
Citation Format: Sarah L. Maguire, Katarzyna Tomczyk, Eleni Perrakis, Edward Saunders, Daniel Leongamornlert, ZSofia Kote-Jarai, Rosalind Eeles, Montserrat Garcia-Closas, Paul Pharoah, Douglas Easton, Christopher J. Lord, Alan Ashworth, Anthony Swerdlow, Nick Orr. Rare variants in DNA damage repair genes are associated with male breast cancer predisposition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1225.
Abstract 1272: Docosahexaenoic acid supplementation enhances the response of PC-3 prostate cancer cells to enzalutamide
Authors: Ma Irvin V. , Cooper Andrew R. , Hu Ying , Sorreta Arianne G. , Bains Palvinder K. , Kumar Prem , Pardini Ronald S. 
Published: August 2018

Abstract
Prostate cancer is currently the second leading cause of death from cancer among men in the United States. Initial treatments generally focus on hormone therapy to inhibit the production of androgens, but most prostate cancers eventually become castration resistant and no longer respond to androgen-suppression therapy. The recent development of drugs that inhibit androgen binding to the androgen receptor (AR) have proven effective in treating castration-resistant prostate cancer (CRPC). Studies in our laboratory have shown that docosahexaenoic acid (DHA; C22:6 n-3), a long chain omega-3 polyunsaturated fatty acid (PUFA), inhibits tumorigenesis in both androgen-dependent (LNCaP) and androgen-independent (PC-3, DU145) prostate cancer cell lines in culture. Moreover, in vivo studies with n-3 PUFA supplementation have been shown to significantly reduce tumor growth of PC-3 and DU145 compared to corn oil diets rich in linoleic acid, (C18:2, n-6). With evidence suggesting that n-3 PUFA dietary supplementation can inhibit tumorigenesis in CRPC, the current study investigated the impact of DHA supplementation in combination with enzalutamide in PC-3 tumor cells. Enzalutamide is a Food and Drug Administration-approved treatment for patients with metastatic CRPC. Enzalutamide acts by interrupting the binding of androgens to the AR, which influences the AR signaling pathway–a target of interest in CRPC treatment. Cell viability was determined by measuring intracellular ATP in PC-3 cells treated with DHA and enzalutamide alone and in combination. Cell viability was reduced with the combination of DHA and enzalutamide compared to enzalutamide or DHA alone, suggesting that DHA enrichment can augment enzalutamide therapy with PC-3 cells in vitro. Studies have also shown that combinatorial treatments with enzalutamide and HIF-1α inhibitors result in synergistic inhibition of CRPC tumor proliferation, and our laboratory has shown that DHA inhibits HIF-1α by decreasing intracellular ATP in breast and lung cancer cells in vitro. These results serve as a prelude to a pilot clinical trial to evaluate the effects of nutritional supplementation with high levels of omega-3 fatty acids on enzalutamide inhibition of CRPC.
Citation Format: Irvin V. Ma, Andrew R. Cooper, Ying Hu, Arianne G. Sorreta, Palvinder K. Bains, Prem Kumar, Ronald S. Pardini. Docosahexaenoic acid supplementation enhances the response of PC-3 prostate cancer cells to enzalutamide [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1272.
Abstract 1273: Effect of a Western diet on colitis-associated colon tumor formation in BALB/c mice
Authors: Groeschel Charlotte , Tennakoon Samawansha , Aggarwal Abhishek , Kallay Enikoe 
Published: August 2018

Abstract
Patients with inflammatory bowel disease (IBD) are at increased risk for inflammation associated colorectal cancer (CAC). The incidence of IBD is increasing in the Western industrialized world. Epidemiological studies suggest that a diet, high in fat but low in vitamin D, calcium, fibre and methyl donors is a risk factor for both, IBD and colorectal cancer (CRC). It has been shown previously that a ”New Western Diet”, caused development of sporadic colonic tumours in mice.
Our study was performed to evaluate whether a Western Diet (WD) aggravates azoxymethane (AOM) /dextran sodium sulfate salt (DSS)-induced colitis-associated carcinogenesis in mice, and if a switch to the standard purified mouse diet AIN93G after cancer initiation is still able to ameliorate or delay the onset of the disease. Female BALB/c mice received either the WD (0.5 mg/g calcium, 2% fibre, 21 % butter fat, 0.23 μg/g folic acid) or AIN93G standard diet for 5 weeks until AOM was administered at a dose of 12.5 μg/kg intraperitoneally, followed by 3 cycles of DSS (2.5%). In one group the WD was switched to AIN93G diet one day before first administration of DSS. The mice were euthanized 80 days after AOM injection. One part of the colon, small intestine, kidney and liver were frozen in liquid nitrogen, the rest formalin fixed and paraffin embedded for mRNA and immunhistochemical analysis. Feeding constantly the WD shortened the colon (p&lt;0.05) and increased the number (p&lt;0.05) and size (p&lt;0.01) of aberrant colonic crypt foci. The switch to the AIN93G diet ameliorated this effect, leading to reduced colitis and tumor promotion comparable with the AIN93G group. In colon ascendens of the WD group, Ki67 protein levels (p&lt;0.001) and relative mRNA levels of the Wnt target genes c-myc (p&lt;0.05) and axin2 (p&lt;0.001) were reduced while mRNA levels of the vitamin D catabolizing enzyme cyp24a1 (p&lt;0.001) and inos (p&lt;0.05) were increased when compared with the AIN93G group.
A healthy diet protects colonic mucosa against AOM/DSS-treatment and is an effective chemopreventive strategy to reduce chronic colonic inflammation and tumorigenesis.
This project is funded by the Vienna Science and Technology Fund and the Austrian Research Fund.
Citation Format: Charlotte Groeschel, Samawansha Tennakoon, Abhishek Aggarwal, Enikoe Kallay. Effect of a Western diet on colitis-associated colon tumor formation in BALB/c mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1273.
Abstract 1288: A comprehensive investigation of factors impacting the accuracy of mutation detection using next generation sequencing technology
Authors: Xiao Wenming , Zhao Yongmei ,   Somatic Mutation Working Group, SEQC2 Consortium
Published: August 2018

Abstract
Next generation sequencing (NGS) allows researchers to survey DNA mutations in tumor cells at very large scales with affordable cost. However, distinguishing tumor cell sub-population mutations from errors due to NGS platform biases, sample preservation effects, assay protocols and suboptimal or incongruous bioinformatics analysis methods is currently complex and difficult. For NGS to be successfully leveraged in a clinical translational manner, increased ability to discriminate between true mutations and artifacts is paramount.
To address this urgent unmet clinical need, we systematically investigated somatic mutation events in paired cell lines (breast cancer and normal) with multiple NGS platforms and protocols to fully characterize factors that affect accuracy, specificity and sensitivity of mutation detection. We applied machine learning algorithms to define high confidence mutation calls with data sets from 8 NGS platforms combined with 9 bioinformatic analysis pipelines. With “ground truth” established using multiple orthogonal sequencing platforms, we evaluated the performance of mutation detection under various circumstances, including: fresh cell vs FFPE, amount of DNA, library preparation, sequencing platform, tumor purity, and analysis algorithm. Moreover, we performed whole exome sequencing (WES) and whole genome sequencing (WGS) at 6 sequencing sites in parallel, which allowed us to assess the reproducibility of NGS runs on the same biological samples.
By analyzing DNA variant detection recall and precision from data sets derived from various conditions, we identified statistical variance components in overall DNA variant detection framework as well as specific practices that will likely lead to the false identification of variants. By concomitantly examining the effects between sample processing and bioinformatics pipelines, here we recommend best practices for mutation detection using NGS technology and establish quality metrics for cancer studies involving NGS technology.
Citation Format: Wenming Xiao, Yongmei Zhao, Somatic Mutation Working Group, SEQC2 Consortium. A comprehensive investigation of factors impacting the accuracy of mutation detection using next generation sequencing technology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1288.
Abstract 13: Anti-angiogenic action of leukotriene-C4induced 15-hydroxyprostaglandin dehydrogenase in colon cancer cells is a TNF-α dependent phenomenon
Authors: Satapathy Shakti R. , Sjölander Anita 
Published: August 2018

Abstract
Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Cyclooxygenase-2 (COX-2), which plays a key role in the biosynthesis of prostaglandin E2 (PGE2), is often up-regulated in CRC and in other types of cancer. PGE2 induces angiogenesis and tumor cell survival, proliferation and migration. The tumor suppressor 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is a key enzyme in PGE2 catabolism, converting it into its inactive metabolite 15-keto-PGE2 and is often down-regulated in cancer. Interesting enough, CRC patients expressing high levels of Cysteinyl leukotriene receptor 2 (CysLTR2) have a good prognosis and therefore, we investigated a potential link between CysLTR2-signaling and the tumor suppressor 15-PGDH in colon cancer cells. TNF-α is considered as the main regulators of COX-2 and mPGES-1 that contribute to the increased synthesis of PGE2, which is inhibited by overexpressed 15-PGDH. Level of the pro-tumorigenic PGE2 are increased in CRC, previously attributed to increased production via TNF-α mediated COX-2 up-regulation but more recently attributed to decreased catabolism due to down-regulation of 15-PGDH. Elevation of 15-PGDH expression by leukotriene C4 (LTC4), a CysLTR2 ligand, exhibited anti-tumor activity in colon cancer cells with significant phosphorylation of β-catenin and down-regulation of anti-apoptotic marker Bcl-2 with concurrent activation of CASPASE-3 expression. We also observed a dramatic down-regulation of TNF-α on mRNA level and NF-κβ on both mRNA as well as protein level with LTC4 induced 15-PGDH in a TNF-α dependent manner. Moreover, TNF-α regulated anti-angiogenic action of 15-PGDH in HT-29 and Caco-2 colon cancer cells by depleting the mRNA level of MMP-2 and MMP-9 and protein level of VEGFR-1. Furthermore, our preliminary observation also suggested disrupted tube formation in HUVEC with LTC4 induced 15-PGDH which is mediated by TNF-α. Hence, restoration of 15-PGDH expression through CysLTR2-signaling promotes the anti-angiogenic action against colon cancer cells, indicating an anti-tumor as well as the anti-metastatic efficacy of CysLTR2-signaling.
Citation Format: Shakti R. Satapathy, Anita Sjölander. Anti-angiogenic action of leukotriene-C4induced 15-hydroxyprostaglandin dehydrogenase in colon cancer cells is a TNF-α dependent phenomenon [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 13.
Abstract 1310: Systematic evaluation of gene networks for discovery of disease genes
Authors: Huang Justin K. , Carlin Daniel E. , Yu Michael K. , Zhang Wei , Kreisberg Jason F. , Tamayo Pablo , Ideker Trey 
Published: August 2018

Abstract
Gene networks are rapidly growing in size and number, raising the question of which networks are most appropriate for a particular application. Here, we evaluate 21 human genome-wide interaction networks for their ability to recover gene sets associated with 446 different diseases and 9 cancer hallmarks. While all networks have some ability in these recovery tasks, we observe a wide range of performance with STRING, GeneMANIA and GIANT networks having the best performance overall. A general tendency is that performance scales with network size, suggesting that new interaction discovery currently outweighs the detrimental effects of false positives. Correcting for size, we find that the DIP network provides the highest efficiency (value per interaction). Based on these results we create a parsimonious composite network with both high efficiency and absolute performance, which outperforms any single resource. This work provides a benchmark for selection of molecular networks in human disease research.
Citation Format: Justin K. Huang, Daniel E. Carlin, Michael K. Yu, Wei Zhang, Jason F. Kreisberg, Pablo Tamayo, Trey Ideker. Systematic evaluation of gene networks for discovery of disease genes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1310.
Abstract 1323: A p53-dependent switch between cytoprotective and nonprotective autophagy influences tumor cell sensitivity to cisplatin
Authors: Xu Jingwen , Saleh Tareq , Patel Nipa , Wu Yingliang , Lima Santiago , Gewirtz David 
Published: August 2018

Abstract
Autophagy is a multi-step, homeostatic process through which cells turnover dysfunctional organelles and proteins. Previous work in our laboratory has identified multiple functional roles of autophagy, specifically cytoprotective, cytotoxic, cytostatic and nonprotective, when subjected to radiation and chemotherapy. Furthermore, we have reported on the existence of an autophagic switch between one functional form (generally cytoprotective) to the other forms. To further explore the autophagic switch, we utilized p53 wild type (p53 +/+) and p53 null (p53 -/-) H460 non-small cell lung cancer (NSCLC) cell lines exposed to cisplatin. The extent of autophagy was similar in both cell lines, but the rate and extent of apoptosis was higher in the p53 +/+ cells, which showed greater cisplatin sensitivity. Pharmacological (chloroquine, 3-Methyladenine) and genetic (ATG5 silencing) inhibition of autophagy failed to sensitize the p53 +/+ H460 cells to cisplatin, suggesting that autophagy has a nonprotective role. In contrast, autophagy inhibition (CQ, 3-MA, or shATG5) increased sensitivity to cisplatin in the p53 -/- H460 cells, indicative of a cytoprotective function of autophagy. These studies support the premise that cytoprotective autophagy may confer resistance to cisplatin. Moreover, we confirm the pivotal role of p53 in determining the function of autophagy induced by cisplatin. Finally, we provide an additional example of a switch between the nonprotective and protective forms of autophagy in p53 wild type and p53 null H460 non-small cell lung cancer (NSCLC) cells, respectively.
Citation Format: Jingwen Xu, Tareq Saleh, Nipa Patel, Yingliang Wu, Santiago Lima, David Gewirtz. A p53-dependent switch between cytoprotective and nonprotective autophagy influences tumor cell sensitivity to cisplatin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1323.