bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 240: Dietary patterns and risk of colorectal neoplasia in Puerto Rican Hispanics: A case control study
Authors: Perez-Mayoral Julyann , Julian Sachelly , Soto-Salgado Marievelisse , Gonzalez Michael J. , Cruz-Correa Marcia 
Published: July 2017

Abstract
Colorectal cancer (CRC) is the leading cause of cancer death in Puerto Rico and second cause of death in the US. It is well accepted that modifiable lifestyle habits such as diet, contribute to CRC development. Diet could reduce up to 70% of CRC cases. Dietary patterns vary according to race/ethnicity. Puerto Rican Hispanics (PRH) have been shown to have a distinct diet compared to US non-Hispanic Whites (NHW). According to the BRFSS, only 17.7% of PRH and 23.4% of NHW consume fruit and vegetables five times per day. The objective of this study was to describe the association of specific food groups consumption with the risk of colorectal neoplasia (CRN: polyps and/or CRC) in PRH. The validated Colon Cancer Family Registry food frequency questionnaire was administered to healthy individuals (controls) and individuals with CRN (cases) recruited through the Puerto Rico Colorectal Cancer Registry (PURIFICAR). Models adjusted by age, gender, educational attainment and family history of CRC were fitted to estimate the odds ratios (OR) with 95% confidence intervals (CI) through a polytomous logistic regression models comparing cases and controls. A total of 577 subjects were included in the study (controls=254; polyps=50; and CRC=273). The frequency of consumption of fruits, low fat dairy products, eggs, pasta/rice, non-fried chicken, and seafood were significantly different between controls and CRN cases (p&lt;0.05). Adjusted models showed that a higher consumption of fruits (OR≥once per day=0.29) and full-fat dairy products (OR≥once per day=0.22) were associated with decreased risk of polyps (p&lt;0.05). A frequency of consumption of 2-4 times per week, when compared to ≤ 1 per week, of full-fat dairy products (OR2-4 times per week=0.51), seafood (OR2-4 times per week=0.49), and red meats (OR2-4 times per week=0.56) was associated with a decreased risk of CRC (p&lt;0.05). Our results showed that a higher consumption of fruits and full-fat dairy products significantly reduce the risk of polyps in PRH. In addition, consumption of seafood, full-fat dairy, and red meats up to 4 times per week may reduce the risk of CRC in PRH. Educational interventions for cancer prevention in PRH should incorporate nutritional information tailor to our community.
Citation Format: Julyann Perez-Mayoral, Sachelly Julian, Marievelisse Soto-Salgado, Michael J. Gonzalez, Marcia Cruz-Correa. Dietary patterns and risk of colorectal neoplasia in Puerto Rican Hispanics: A case control 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 240. doi:10.1158/1538-7445.AM2017-240
Abstract 2408: Epigenomic characterization of MSC from myeloid malignancies
Authors: Rodríguez-Paredes Manuel , Geyh Stefanie , Gazorpak Mahshid , Gutekunst Julian , Bormann Felix , Haas Rainer , Schröder Thomas , Lyko Frank 
Published: July 2017

Abstract
Ineffective hematopoiesis is a hallmark of myeloid malignancies such as Myelodysplastic Syndromes (MDS) or Acute Myeloid Leukemia (AML). Our previous research has shown that mesenchymal stromal cells (MSC), one of the main cellular regulatory components of the bone marrow niche and essential for the differentiation of new blood cells from Hematopoietic Stem Cells (HSC), are molecularly and functionally impaired in MDS and AML patients. More specifically, these cells display reduced proliferative and differentiation capacities, an increased cellular senescence, or the altered expression of key hematopoietic factors, defects that can provide an explanation for the cytopenia associated with these diseases. But most interestingly, we have also discovered that MDS- and AML-derived MSC present aberrant methylomes. Our data, based on 450k DNA methylation microarrays, show that these abnormalities are shared by the MSC from both malignancies and affect key transcription factors like TBX15, PITX2 or HOXB6, formerly linked to differentiation and development. This results can account for some of the defects observed in the disease-related MSC and represent an important paradigm for cancer-induced epigenetic changes in normal cells. Aiming to further explore the importance of this epigenetic deregulation, we performed RNAseq experiments using MSC from healthy donors as well as from MDS and AML patients. This approach not only suggests a profound impact of the epigenetic aberrancies on gene expression, but also allowed us to identify TGFβ as the soluble factor that, released by the malignant cells in the bone marrow, appears to trigger the above-mentioned defects in the MDS- and AML-derived MSC. Indeed, our results show that, when treated with TGFβ, healthy MSC undergo the deregulation of TBX15, PITX2 or HOXB6 and develop some of the observed aberrant phenotypes. Conversely, the treatment of MDS- and AML-derived MSC with a TGFβ antagonist like SD208 can abrogate these effects. Finally, our preliminary DNA methylation data reveal a very similar deregulation in the methylome of MSC from Multiple Myeloma (MM) patients, strongly suggesting that the same scenario could also be common to other hematological malignancies from the lymphoid branch.
Citation Format: Manuel Rodríguez-Paredes, Stefanie Geyh, Mahshid Gazorpak, Julian Gutekunst, Felix Bormann, Rainer Haas, Thomas Schröder, Frank Lyko. Epigenomic characterization of MSC from myeloid malignancies [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 2408. doi:10.1158/1538-7445.AM2017-2408
Abstract 2410: Toward mutation analysis of regulatory elements: Epigenetic profiling of primary breast tumors
Authors: Ghamrasni Samah El , Guilhamon Paul , Quevedo Rene , Yang Cindy , Lupien Mathieu , Pugh Trevor 
Published: July 2017

Abstract
Non-coding mutations found in regulatory elements can function as driver mutations in breast cancer by changing the binding affinity of transcription factors for DNA, thereby resulting in direct change of expression of genes that promote cancer development. Identifying such additional driver mutations can reveal the molecular mechanisms favorable to breast cancer development and progression, as well as reveal new biomarkers to better tailor personalized/precision cancer medicine. In this study we have collected 20 primary luminal breast tumors and optimized experimental workflow to dissociate solid tumors and map open chromatin using ATAC-seq. In our initial experiments using ATAC-seq profiling of bulk tumor tissues, we were able to call an average of 15x103 peaks. Subsequently, flow cytometry analysis showed the presence of 15-25% of immune cells in our primary tumors. Therefore, we have optimized a workflow to eliminate immune cells and focus mainly on epithelial tumor cells. Primary breast tumors were digested using collagenase and further dissociated with dispase. Cells were sorted into two populations (mammary epithelial and immune cells) using anti-CD45, anti-CD49f and anti-EpCAM antibodies. Sorted mammary epithelial cells were then used for ATAC- and RNA-seq library preparation as well as for generation of patient derived organoids. Our new workflow resulted in an increased number of called peaks (40x103 vs 15x103), as well as a significant increase in the percentage of unique peaks compared to bulk sequencing (45% vs 15%). By refining our workflow to enrich for tumour content, we will continue our ongoing effort to profile these open chromatin regions and contextualize the mutations within in a large cohort of luminal breast cancers using targeted sequencing. These data will be compared with large-scale whole genome data generated by our group and made publicly available by others.
Citation Format: Samah El Ghamrasni, Paul Guilhamon, Rene Quevedo, Cindy Yang, Mathieu Lupien, Trevor Pugh. Toward mutation analysis of regulatory elements: Epigenetic profiling of primary breast tumors [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 2410. doi:10.1158/1538-7445.AM2017-2410
Abstract 2411: The role of A-to-I RNA editing in human cancer
Authors: Liang Han 
Published: July 2017

Abstract
Recent studies show that A-to-I RNA editing introduces a large number of specific nucleotide changes in cancer transcriptomes. Using the genomic/transcriptomic data from The Cancer Genome Atlas, we systematically characterized the landscape of RNA editing in a variety of cancer types and revealed many sites with clinically relevant patterns. We further integrated proteomic data from the Clinical Proteomic Tumor Analysis Consortium and found that mutations and RNA editing introduced similar numbers of amino acids changes per tumor sample in breast and ovarian cancers. The amino acid changes engendered by these RNA editing events may significantly alter protein stability. Some of the identified RNA editing events show critical consequent changes driving tumor growth and altering therapeutic activity. We also identified the RNA editing hotspots in miRNAs across cancer types, and some of RNA editing events modify the miRNA target genes. They could function as potential therapeutic targets and therapeutics. Our study suggests a large contribution of A-to-I RNA editing to protein diversity and gene regulation, and highlights its translational potential as both biomarkers and therapeutic targets.
Citation Format: Han Liang. The role of A-to-I RNA editing in human 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 2411. doi:10.1158/1538-7445.AM2017-2411
Abstract 2413: SIRT1 regulates Mxd1 throughout melanoma progression
Authors: Meliso Fabiana M. , Micali Danilo , Silva Camila T. , Sabedot Thais S. , Coetzee Simon G. , Koch Adrian , Fahlbusch Fabian B. , Noushmehr Houtan , Schneider-Stock Regine , Jasiulionis Miriam G. 
Published: July 2017

Abstract
In a murine melanoma model of malignant transformation promoted by sustained stress, increased levels of reactive oxygen species were found to result in DNA damage and were related to massive epigenetic alterations. Since the chromatin modifier Sirtuin-1 (SIRT1) is a protein attracted to double-stranded DNA break (DSB) sites and can recruit other components of the epigenetic machinery, we aimed to define the role of SIRT1 in melanomagenesis through our melanoma model. The DNA damage marker, γH2AX was found increased in melanocytes after 24 hours of deadhesion, accompanied by increased SIRT1 expression and decreased levels of its target, H4K16ac. Moreover, SIRT1 started to be associated to DNMT3B during the stress condition, and this complex was maintained along malignant progression. Mxd1 was identified by ChIP-seq among the DNA sequences differentially associated with SIRT1 during deadhesion and was shown to be a common target of both, SIRT1 and DNMT3B. In addition, Mxd1 was found down-regulated from pre-malignant melanocytes to metastatic melanoma cells. Treatment with DNMT inhibitor 5AzaCdR reversed the Mxd1 expression. Sirt1 stable silencing increased Mxd1 mRNA expression and led to up-regulation of MYC targets, such as Cdkn1a, Bcl2 and Psen2, the upregulation of which is associated with human melanoma aggressiveness and poor prognosis. We demonstrated a novel role of the stress responsive protein SIRT1 in malignant transformation of melanocytes associated with deadhesion. Mxd1 was identified as a new SIRT1 target gene. SIRT1 promoted Mxd1 silencing, which led to increased activity of MYC oncogene contributing to melanoma progression.
Citation Format: Fabiana M. Meliso, Danilo Micali, Camila T. Silva, Thais S. Sabedot, Simon G. Coetzee, Adrian Koch, Fabian B. Fahlbusch, Houtan Noushmehr, Regine Schneider-Stock, Miriam G. Jasiulionis. SIRT1 regulates Mxd1 throughout melanoma progression [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 2413. doi:10.1158/1538-7445.AM2017-2413
Abstract 2467: Mutation analysis using next-generation sequencing in histologically heterogeneous of primary lung cancers
Authors: Koba Hayato , Kimura Hideharu , Kasahara Kazuo 
Published: July 2017

Abstract
Rare cases of primary lung cancer are known to have different histological types. Recently, small cell carcinoma was reported to be developed in adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutations after EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment. The purposes of this study are to evaluate mutational status in two different histological types separately, and to further understand the molecular pathogenesis. Twelve tumor samples from 6 patients were collected in our institution. 4 patients had primary adenocarcinoma and small cell carcinoma transformed after EGFR-TKI. One patient had primary adenocarcinoma and squamous cell carcinoma transformed after EGFR-TKI. The other one patient had carcinosarcoma in a surgically resected tumor. Two samples per patient were collected from histologically different areas within a resected tumor or the 2 distinct metastatic sites. DNA was extracted from formalin-fixed, paraffin-embedded tumor tissues. Next-generation sequencings in the 12 samples were performed on 160 cancer-related genes using GeneRead™ DNAseq Targeted Panels V2 Human comprehensive Cancer Panel (QIAGEN). In a carcinosarcoma case with deletional mutation in EGFR gene, a total 504 in adenocarcinoma and 595 in sarcoma variants in 160 genes were detected with high confidence. The gene of identical alterations, as truncal alterations, were EGFR, CBLB, TP53 and MEN1 and the number of that as an unique alteration corresponding to each histology is 25 for adenocarcinoma and 85 for sarcoma. We show relations between the histological types and the genomic alterations, identical alterations and unique alterations, in each patient. Furthermore, we raise essential factors for the histological transformation.
Citation Format: Hayato Koba, Hideharu Kimura, Kazuo Kasahara. Mutation analysis using next-generation sequencing in histologically heterogeneous of primary lung cancers [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 2467. doi:10.1158/1538-7445.AM2017-2467
Abstract 2551: Long noncoding RNA HOXA11 antisense promotes tumor progression via the Notch pathway in serous ovarian cancer
Authors: Kim Hee Jung , Yim Ga Won , Eoh Kyung Jin , Kim Lee Kyung , Lee Jung-Yun , Nam Eun Ji , Kim Sang Wun , Kim Young Tae 
Published: July 2017

Abstract
The biological function of long noncoding RNAs (lncRNAs) is only partially understood. We investigated the expression of the novel HOXA11 antisense (HOXA11as) lncRNA and its oncogenic role in serous ovarian cancer (SOC). HOXA11as expression was examined in 129 serous ovarian cancer tissue samples by real time RT-PCR. Clinicopathologic factors and patient survival were compared between high (N = 27) and low HOXA11as expression group (N = 102). To investigate the role of HOXA11as in cell proliferation, invasion, and migration, HOXA11as expression in ovarian cancer cells was knocked down using RNA interference. HOXA11as expression in cancer tissue was 77-fold higher than that of noncancerous tissue (P &lt; 0.05). Higher HOXA11as expression significantly correlated with histologic grade (P = 0.017) and preoperative CA125 (P = 0.048). HOXA11as overexpression in SOC cells led to increased cell proliferation, invasion, and migration. In addition, HOXA11as was associated with the expression of genes that involve in cell proliferation, invasion, and migration. Moreover, Knockdown of HOXA11as decreased the expression of vascular endothelial growth factor, matrix metalloproteinase-9 and epithelial-mesenchymal transition (EMT), which are important for cell motility and metastasis. Mechanistic investigation revealed that Notch1, Hes1 and p300 proteins could be inhibited by HOXA11as depletion. In multivariate analysis, HOXA11as was a prognostic factor of progressive disease and mortality (HR = 1.730, 2.170 and P = 0.043, 0.033, respectively). Progression-free and overall survival were significantly shorter in patients with high HOXA11as expression. These findings highlight the clinical significance of HOXA11as in predicting the prognosis of SOC patients and suggest its potential in promoting tumor aggressiveness by regulation of the Notch signaling pathway and EMT-related mechanisms.
Note: This abstract was not presented at the meeting.
Citation Format: Hee Jung Kim, Ga Won Yim, Kyung Jin Eoh, Lee Kyung Kim, Jung-Yun Lee, Eun Ji Nam, Sang Wun Kim, Young Tae Kim. Long noncoding RNA HOXA11 antisense promotes tumor progression via the Notch pathway in serous ovarian 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 2551. doi:10.1158/1538-7445.AM2017-2551
Abstract 2552: MDM2 induces cell fusion in breast cancer and osteosarcoma
Authors: Olivos David J. , Chtcherbinine Mikhail , Wolf Eric R. , McAtarsney Ciarán , Mayo Lindsey D. 
Published: July 2017

Abstract
Cell fusion is a physiological process utilized by a variety of biological systems during fertilization, embryogenesis, and cellular differentiation and morphogenesis. During the malignant transformation of breast and bone tissues, normal and malignant cells become fused to form hybrid structures. These enhanced phenotypes acquire genetic characteristics which support initiation, progression, and oncogenesis. In breast cancer and osteosarcoma cell lines, cell fusion generates chromosomal instability, aneuploidy, and DNA damage while maintaining the characteristics of enhanced migration, invasion, and chemoresistance. We have found that mouse double minute 2 (Mdm2) significantly induces cell fusion and the generation of large multinucleated cells in MDA468, MDA231, MDA157, T47D breast cancer and MG63 osteosarcoma cell lines under normoxia when compared to silenced Mdm2 controls (P&lt;0.0005). Interestingly, silencing mutant p53 in the MDA468 cell line resulted in significantly higher fusion events (P&lt;0.0004) suggesting mutant p53 may play a regulatory role in reducing Mdm2-associated cell fusion. Silenced Mdm2 MDA231 cells showed a three-fold increase under hypoxia whereas MG63 cells showed similar levels of cell fusion events as in normoxic conditions suggesting cell specific dependency to environmental stimulus. The variation in proportions of cell fusion among each cell type suggests this phenomenon is dependent on Mdm2 expression and cell type. CD133+ MDA468 cells have increased fractions of polyploidal cell events suggesting stemness may influence the polyploidal giant cancer cell (PGCC) dynamics. The mechanism by which cell fusion occurs in breast and osteosarcoma is poorly understood. Collectively these data suggest the interplay of Mdm2, p53, and stemness in supporting the formation of fused polypoidal cells and may serve as relevant targets for cancer therapy.
Citation Format: David J. Olivos, Mikhail Chtcherbinine, Eric R. Wolf, Ciarán McAtarsney, Lindsey D. Mayo. MDM2 induces cell fusion in breast cancer and osteosarcoma [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 2552. doi:10.1158/1538-7445.AM2017-2552
Abstract 2581: VGLL4 suppresses the human breast cancer progression through the inhibition of YAP oncogenic function
Authors: Zhang Jianmin 
Published: July 2017

Abstract
VGLL4 is a Vestigial-like (VGLL) protein that is deregulated in various types of cancer. However, the functions of VGLL4 in breast cancer remain largely unknown. Here, we demonstrate that VGLL4 expression positively correlates with survival for breast cancer patients. The overexpression of VGLL4 in breast cancer cells reduced cell proliferation, colony formation, cell migration and invasion in vitro and inhibited tumor growth in vivo. We found that the 2nd TEAD-interacting domain (TDU2) of VGLL4 is involved in interactions between VGLL4 and the transcription factor TEAD and that the deletion of this domain completely abolished the phenotype induced by VGLL4 overexpression. Interestingly, RNAseq analysis indicated that VGLL4 overexpression not only inhibits YAP targets but also activates the TGF-β and Notch signaling pathways. Our study provides evidence of the tumor-suppressive effects of VGLL4 on breast cancer progression and suggests that VGLL4 and its TDU2 domain may become promising and efficient therapeutic targets for delaying the development of breast cancer and improving patient survival.
Citation Format: Jianmin Zhang. VGLL4 suppresses the human breast cancer progression through the inhibition of YAP oncogenic function [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 2581. doi:10.1158/1538-7445.AM2017-2581