bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4645: Lifestyle and dietary oxidative balance scores and risk for incident colorectal cancer among older women: The Iowa Women's Health Study
Authors: Mao Ziling , Prizment Anna E. , Lazovich DeAnn , Gibbs David C. , Bostick Roberd M. 
Published: September 2020

Abstract
Background: Basic science literature strongly supports a role of oxidative stress in colorectal cancer (CRC) etiology; however, in epidemiologic studies, associations of individual lifestyle and dietary anti- and pro-oxidant exposures with CRC have been largely inconsistent. However, recent epidemiologic evidence suggests that the collective effects of these exposures on oxidative balance and CRC risk may be substantial.
Methods: From lifestyle and food frequency questionnaire data from the prospective Iowa Women's Health Study (1986 - 2012), we calculated equal-weight, 4-component lifestyle and 11-component dietary oxidative balance scores (OBS), and investigated their separate and joint associations with incident CRC using multivariable Cox proportional hazards regression.
Results: Of the 34,135 cancer-free women aged 55 to 69 at baseline, 1,635 developed CRC during follow-up. Among participants in the highest lifestyle and dietary OBS quintiles (higher anti-oxidant relative to pro-oxidant exposures) relative to the lowest, the multivariable-adjusted hazard ratios (HRs) were, respectively, 0.63 (95% confidence interval (CI), 0.54-0.73; Ptrend &lt; 0.0001) and 0.77 (95% CI, 0.64-0.94; Ptrend = 0.01. The lowest risk was among those in the highest relative to the lowest joint lifestyle/dietary OBS quintile (HR = 0.47; 95% CI, 0.29-0.76).
Conclusions: Our findings suggest that a predominance of antioxidant over pro-oxidant lifestyle and dietary exposures–especially lifestyle separately and jointly with dietary exposures–may be inversely associated with CRC risk among older women.
Citation Format: Ziling Mao, Anna E. Prizment, DeAnn Lazovich, David C. Gibbs, Roberd M. Bostick. Lifestyle and dietary oxidative balance scores and risk for incident colorectal cancer among older women: The Iowa Women's Health Study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4645.
Abstract 4687: Oncogenic role of the transcription factor YY1 and its target Survivin in non-Hodgkin's lymphoma
Authors: Vivarelli Silvia , Falzone Luca , Candido Saverio , Bonavida Benjamin , Libra Massimo 
Published: September 2020

Abstract
Objective
Yin Yang 1 (YY1) is a transcription factor with a dual role in cancer genesis. Hematological malignancies, including non-Hodgkin lymphomas (NHL), are often characterized by a frequent development of resistance to therapy and a high rate of tumor recurrence. Our previous observations showed that YY1 is overexpressed in hematological tumors. The aim of this study was to investigate the functional role of YY1 in anti-cancer therapy induced cell death and to identify YY1 downstream resistant factors.
Experimental Designs
The NHL Raji cell line was used as a cellular model. The expression of YY1 was assessed by q-PCR and WB. YY1 knock-down (KD) was achieved using retroviral shRNA. Viability was measured by both the MTT assay and the Trypan Blue live/dead cell count. Cell death was induced following Vincristine and Doxorubicin treatments. The following analyses were used in this study: the JASPAR database, the Encyclopedia of DNA Elements (ENCODE) and the Cancer Genome Atlas (TCGA) datasets relative to NHL patients have been analyzed to assess the expression levels of YY1 and apoptotic genes, according to tumor stages and patients' clinical-pathological features.
Results
Silencing of YY1 in Raji cells resulted in increased sensitivity to both Vincristine and Doxorubicin treatments and augmented apoptosis. Jaspar analysis identified several potential YY1 transcriptional targets involved in cellular death regulation. As a result of q-PCR screening and validation, Survivin has been identified as a potential YY1 target, as it was significantly downregulated following YY1 KD. Bioinformatic analysis of deposited Chip-Seq databases in ENCODE revealed that YY1 is able to target Survivin transcriptional regulatory regions in different cancer cell lines, as well as in normal B lymphocytes. The TCGA-deposited datasets identified specific clusters of YY1 expression significantly correlated with Survivin.
Conclusions
Our findings demonstrated that (1) YY1 silencing resulted in the sensitization of Raji tumor cells to drug-induced apoptosis (2) q-PCR-mediated screening of putative YY1 targets led to the identification of Survivin as a potential YY1 target, as when YY1 was KD, Survivin levels were strongly downregulated (3) YY1 might be positively regulating Survivin expression (4) Survivin could be a potential target of YY1 in NHL and (5) YY1 and Survivin in NHL may represent two novel diagnostic and prognostic biomarkers to assess patients' response to chemotherapy.
Citation Format: Silvia Vivarelli, Luca Falzone, Saverio Candido, Benjamin Bonavida, Massimo Libra. Oncogenic role of the transcription factor YY1 and its target Survivin in non-Hodgkin's lymphoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4687.
Abstract 470: High-dose TSLP decreases in vivo tumor burden in preclinical models of CRLF2 B-ALL
Authors: Ruiz-Jimenez Caleb , Coats Jacqueline , Stoian Cornelia , Baez Ineavely , Alkashgari Hossam , Paz-Aldana Andy , Choi Hannah , Williams Roland , Gohar Shadi Farzin , Dovat Sinisa , Payne Kimberly 
Published: September 2020

Abstract
B cell acute lymphoblastic leukemia (B-ALL) is the most common cancer in pediatric patients and children of Hispanic ancestry experience higher incidence and mortality rates than others. While cure rates approach 90%, approximately 10% to 20% of patients still relapse. Genomic profiling has identified Ph-like B-ALL as the subtype at highest risk for relapse. Half of all Ph-like B-ALL overexpress the CRLF2 surface protein (CRLF2+ B-ALL). CRLF2 homodimerizes with the IL-7 receptor alpha (IL-7Ra) to comprise a receptor complex that is activated by the cytokine, Thymic Stromal Lymphopoietin (TSLP). TSLP activates the JAK/STAT and PI3/AKT/mTOR pathways which are known to promote cell survival and proliferation. In vitro studies of CRLF2 B-ALL in our laboratory showed that physiological levels (20 pg/ml) of TSLP could activate the TSLP receptor (indicated by STAT5 and ribosomal protein S6 phosphorylation) when stimulated over time. In contrast, we found that supra-physiological levels of TSLP (1 ng/ml or less) induced an initial activation event, but this was followed by a complete shutdown of CRLF2 downstream signaling events that was maintained in the presence of high TSLP. This signal shutdown was correlated with the loss of surface IL-7Ra. The work presented here evaluates the impact of high dose TSLP vs. physiological levels of TSLP on CRLF2 B-ALL in vivo. We make use of novel PDX/xenograft models that expresses human TSLP (hTSLP, mouse TSLP does not activate human CRFL2) created in our lab. Using in vivo bioluminescence analysis of xenografts produced from the MUTZ5 CRLF2 B-ALL cell line, we found that high dose hTSLP induced an 82% decrease in tumor burden (p &lt; 0.0001) as compared to controls with physiological levels of hTSLP. Ongoing studies are evaluating the effect of high dose TSLP on leukemia burden and prolonged survival in a PDX model produced from a Hispanic pediatric patient with CRLF2 B-ALL. Results from these studies will be presented. Taken together, these data suggest that TSLP has promise as a biologic for the treatment of CRLF2 B-ALL.
This work was supported by NIH NCI award R01 CA209829 (KJP & SD).
Citation Format: Caleb Ruiz-Jimenez, Jacqueline Coats, Cornelia Stoian, Ineavely Baez, Hossam Alkashgari, Andy Paz-Aldana, Hannah Choi, Roland Williams, Shadi Farzin Gohar, Sinisa Dovat, Kimberly Payne. High-dose TSLP decreases in vivo tumor burden in preclinical models of CRLF2 B-ALL [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 470.
Abstract 4702: DNA methylation enhances apoptosis resistance of renal cancer cells through the control of mitochondria related gene expression
Authors: Miyakuni Kosuke , Nishida Jun , Ehata Shogo , Miyazono Kohei 
Published: September 2020

Abstract
Many gene alterations have been identified in the onset of renal carcinogenesis. However, molecular alterations might be added to renal cancer cells during the progression. In order to uncover additional molecular alterations, we established highly malignant cancer cells which possess identical background to original cancer cells, and analyzed them in the present study. Since our previous works demonstrated that interaction with cancer microenvironment aids cancer cells with malignant trait through “education” and “selection”, serial orthotopic transplantation was utilized. First, parental human clear cell renal cell carcinoma cells, OS-RC-2, were subjected to serial orthotopic transplantation. Then, novel derivatives were obtained from resulting primary renal tumors. These derivatives formed primary renal tumor faster than parental cells and exhibited increased lung metastasis, suggesting that these derivatives were defined as “highly malignant cancer cells”. Next, we tried to identify the underlying molecular mechanism(s) for renal cancer progression through the characterization of highly malignant cancer cells. Gene expressions in each cell were profiled using RNA-sequencing, and these analyses revealed that expression of several genes associated with mitochondrial functions were dramatically down-regulated in highly malignant cancer cells. Since mitochondrial electron transport chain triggers apoptotic cell death, decrease of these genes may contribute to suppression of apoptosis of highly malignant cancer cells. Cell culture and in vivo experiments demonstrated that mitochondrial dysfunction is responsible for increased survival of renal cancer cells and cancer metastasis. Finally, regulatory mechanism of downregulation of these mitochondria-related genes was analyzed. Bisulfite sequencing analysis revealed that the downregulation may occur by DNA hypermethylation of CpG islands in the promoter regions in renal cancer cells.Taken together, these findings suggested that renal cancer cells acquire additional anti-apoptotic ability through the DNA methylation during the interactions with renal microenvironment, which may in turn lead to the cancer progression and metastasis. We are currently investigating whether the effect of anti-cancer reagent is enhanced in the presence of DNA methylation inhibitors.
Citation Format: Kosuke Miyakuni, Jun Nishida, Shogo Ehata, Kohei Miyazono. DNA methylation enhances apoptosis resistance of renal cancer cells through the control of mitochondria related gene expression [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4702.
Abstract 4703: Role of REST in the regulation of MMP24 and estrogen sensitivity in breast cancer
Authors: Vargheese Aditya M. , Cloud Ashley , Gunewardena Sumedha , Shimak Raeann , Kumaraswamy Easwari , Jensen Roy A. , Chennathukuzhi Vargheese M. 
Published: September 2020

Abstract
Breast cancer, the most common malignancy in women, is very difficult to detect and treat due to its heterogeneity. An important subset of breast cancers, Luminal or ER/PR positive tumors, lack REST (repressor element 1 silencing transcription factor) protein but not its mRNA. REST is a tumor suppressor and is known to play a role in regulating neurodegenerative diseases such as Alzheimer's. The loss of REST leads to the dysregulation of its target genes, many of which are involved in tumorigenesis. About 20% of breast cancers show loss of REST expression, yet little to nothing is currently known about the role REST plays in tumor growth. We hypothesized that the loss of REST promotes breast cancer growth by altering cell signaling. Our results show that knockdown of REST in MCF7 cells (ER/PR positive) causes similar gene dysregulation as seen in aggressive forms of breast cancers. Also, Ingenuity Pathway Analysis (IPA®) of our RNA sequencing results showed that REST knockdown leads to significant increase in estrogen receptor signaling in MCF7 cells. Upregulation of estrogen receptor expression has been associated with tumor progression. In addition, REST knockdown led to significant increases in the expression of MMP24 (&gt;20-fold, p&lt;10−85), a matrix modifying enzyme which could play a role in tumor metastasis, as well as KCNK3 (19-fold, p&lt;10−40), a biomarker associated with poor patient survival. Thus, the poor survival of patients with RESTless breast cancers may be related to the activation of its target genes and elevated estrogen receptor signaling. Furthermore, these patients may respond differently to estrogen receptor antagonists compared to those with REST positive breast cancers. Our results will help with the future development of individualized therapies for breast cancer.
Citation Format: Aditya M. Vargheese, Ashley Cloud, Sumedha Gunewardena, Raeann Shimak, Easwari Kumaraswamy, Roy A. Jensen, Vargheese M. Chennathukuzhi. Role of REST in the regulation of MMP24 and estrogen sensitivity in breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4703.
Abstract 4729: Identifying genomic drivers of lung adenocarcinoma brain metastases
Authors: Nayyar Naema , Shih David J. , Bihun Ivanna , Dagogo-Jack Ibiayi , Gill Corey M. , Aquilanti Elisa , Bertalan Mia , Kaplan Alexander , D'Andrea Megan R. , Chukwueke Ugonma , Alvarez-Breckenridge Christopher , Lastrapes Matthew , Kuter Ben , Strickland Matthew R. , Martinez-Gutierrez Juan Carlos , Nagabhushan Deepika , De Sauvage Magali , White Michael D. , Castro Brandyn A. , Hoang Kaitlin , Paek Sun Ha , Park Sun Hye , Martinez-Lage Maria , Berghoff Anna S. , Merrill Parker , Gerstner Elizabeth R. , Batchelor Tracy T. , Frosch Matthew P. , Frazier Ryan P. , Borger Darrell R. , Iafrate A John , Santagata Sandro , Preusser Matthias , Cahill Daniel P. , Carter Scott L. , Brastianos Priscilla K. 
Published: September 2020

Abstract
Although lung adenocarcinomas frequently metastasize to the brain, treatment options for lung adenocarcinoma brain metastases (BM-LUAD) are limited. We discovered novel candidate drivers of progression by using case-control analyses to compare whole-exome sequencing data from a cohort of 73 BM-LUAD to a control cohort of 503 primary lung adenocarcinomas. We identified MYC, YAP1 and MMP13 as genomic regions with significantly more frequent amplifications in BM-LUAD compared to control cohort. We validated that MYC, YAP1 and MMP13 can drive brain metastases in a patient-derived xenograft mouse model, where incidence of brain metastases was higher in mice injected with tumor cells expressing the candidate drivers compared to tumor cells expressing LacZ. These results indicate that somatic alterations can drive lung adenocarcinomas to metastasize to the brain. These candidate drivers may serve as therapeutic targets in patients with brain metastatic lung adenocarcinomas.
Citation Format: Naema Nayyar, David J. Shih, Ivanna Bihun, Ibiayi Dagogo-Jack, Corey M. Gill, Elisa Aquilanti, Mia Bertalan, Alexander Kaplan, Megan R. D'Andrea, Ugonma Chukwueke, Christopher Alvarez-Breckenridge, Matthew Lastrapes, Ben Kuter, Matthew R. Strickland, Juan Carlos Martinez-Gutierrez, Deepika Nagabhushan, Magali De Sauvage, Michael D. White, Brandyn A. Castro, Kaitlin Hoang, Sun Ha Paek, Sun Hye Park, Maria Martinez-Lage, Anna S. Berghoff, Parker Merrill, Elizabeth R. Gerstner, Tracy T. Batchelor, Matthew P. Frosch, Ryan P. Frazier, Darrell R. Borger, A John Iafrate, Sandro Santagata, Matthias Preusser, Daniel P. Cahill, Scott L. Carter, Priscilla K. Brastianos. Identifying genomic drivers of lung adenocarcinoma brain metastases [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4729.
Abstract 4740: Molecular profiling of adenoid cystic carcinomas
Authors: Ellis Michelle , Swensen Jeff , Stafford Phillip , Gatalica Zoran 
Published: September 2020

Abstract
Introduction: Adenoid cystic carcinomas (AdCC) are uncommon malignant neoplasm that can occur in different locations throughout the body. These tumors are typically characterized by the presence of MYB:NFIB or MYBL1:NFIB fusion, but not in every case.
Methods: We analyzed 107 adenoid cystic carcinomas from various primary sites that were genetically profiled using a large NGS panel (592) genes in genomic DNA and whole transcriptome sequencing. Immunohistochemical staining was performed for PD-L1.
Results: The primary sites included salivary gland (60), lung (15), sino-nasal passages (10), oral cavity (9) breast (5), head, face or neck or other sites (5), skin (1), vulva (1), and unknown primary site (1). Fusions were detected in 87 cases (81%). The two fusions known to be associated with AdCC, MYB:NFIB and MYBL1:NFIB, were detected in 67 specimens (56 MYB:NFIB, 11 MYBL1:NFIB). In addition several fusions of uncertain significance involving these genes were detected (each found in one sample): MYBL1:SGK3, CD274:NFIB, NFIB:AHI1, NFIB:LINC00271 and TOP2B:MYBL1.
No fusions were detected in 20 AdCC; the most common primary sites being salivary glands (14) and lung (4). The most common mutations detected in genomic DNA from these specimens involved NOTCH1 (5 cases), KDM6A (4 cases) ARID1A and TP53 (3 cases each). Two lung primaries were PD-L1 positive, low expression. No pathogenic mutations were detected in 3 cases: 2 salivary gland tumors and 1 oral cavity tumor.
In cases with MYBL1:NFIB fusion, the gene expression of MYB is in the lower 20th percentile (relative to the entire cohort) while MYBL1 expression is in the upper 80th percentile. Conversely in cases with the MYB:NFIB fusions, MYB expression is ectopic resulting in expression in the upper 80th percentile while MYLB1 in the lower 20th percentile.
Conclusion: We detected a classic MYB:NFIB or MYBL1:NFIB fusion in 67 of 107 adenoid cystic carcinomas profiled in this study. There is a strong pattern linking the presence or absence of fusions with the expression of MYB and MYBL1. Thus, fusions are driving high expression of either MYB or MYBL1, but the gene not involved in the fusion shows evidence of reduced expression. We hypothesize that a negative feedback mechanism may result in reduced expression of the other MYB-family gene to maintain homeostasis. From the treatment perspective, rare primary lung AdCC are amenable for I-O therapy based on expression of PD-L1.
Citation Format: Michelle Ellis, Jeff Swensen, Phillip Stafford, Zoran Gatalica. Molecular profiling of adenoid cystic carcinomas [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4740.
Abstract 475: Preoperativechemoradiation increases levels of immune system modulators in tumor tissue in locally advanced rectal cancer
Authors: Bae SungUk , Kim Shin , Lee Hye Won , Byun Sang Jun , Park Jee Young , Min Hyeonji 
Published: September 2020

Abstract
Purpose: Neoadjuvant chemoradiation therapy (CRT) is a widely and effectively used preoperative treatment strategy in locally advanced rectal cancers. However, little research has been done to characterize the molecular changes caused by neoadjuvant CRT in these cancer tissues. The purpose of this study was to investigate the effects of preoperative CRT on tumor gene expression in Korean patients with colorectal cancer (CRC).
Materials and methods: We included 11 paired human rectal cancer tissues before and after irradiation between August 2016 and December 2017, and performed RNA sequencing analysis. Principal component analysis of CRC demonstrated strong similarity in respective groups of CRC tissues before and after CRT from CRC patients at the transcriptome level.
Results: Volcano plot filtering identified 3325 differentially expressed genes (DEGs) in CRC tissues after CRT, compared to CRC tissues before CRT. Gene set enrichment analysis with DEGs revealed 45 signaling pathways associated with down-regulated target genes, significantly including the mismatch repair signaling pathway. CRT significantly increased tumor mutation burden (TMB) in CRC tissues. Notably, preoperative CRT increased immune signature scores including interferon-gamma, immune cytolytic score, and immune signature.
Conclusion: Neoadjuvant CRT modulates immune-related characteristics of CRC, including increasing TMB and various immune signature scores, suggesting that neoadjuvant CRT has potential to improve responsiveness to immunotherapy.
Citation Format: SungUk Bae, Shin Kim, Hye Won Lee, Sang Jun Byun, Jee Young Park, Hyeonji Min. Preoperativechemoradiation increases levels of immune system modulators in tumor tissue in locally advanced rectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 475.
Abstract 4755: Chemoprevention and pharmacokinetics study using Gasdermin D knock out induced colon cancer model mouse treated with FAS inhibitors
Authors: Orita Hajime , Lee Hyeoncheol , Kobayashi Toshiyuki , Fukunaga Tetsu 
Published: September 2020

Abstract
(Introduction) It is well known that cancer cell harness different metabolic pathway from normal cells more efficiently. Recent studies indicate disorder of lipid metabolism has happen even in the benign cell, and that cause to be malignancy. Our research group focus attention on irregular accumulation of fatty acid in cancer cells. This time, we analysis several studies using Gasdermin D knock out induced colon cancer model mouse treated with FAS inhibitors.
1) metabolism analysis for mouse colon cancer. 2) Colon cancer treatment and chemoprevention by FAS inhibitor 3)Pharmacokinetics status of FAS inhibitor (colon cancer model mouse) Gasdermin D (GSDM D), pylotosis key factor, knockout mouse treat with AOM and DSS. 3month after all mouse has several big tumors (patent in Japan 2016-69775)
(Result) 1) There are Many famous long chain fatty acids in cancer tissue. And also Very Long Chain Fatty Acid (:VLCFA) can detected by this analysis. 2) C75 and Kampo (include Berberine) can decrease tumor number and size. And they has chemoprevention effects, too. 3) Almost 40% FAS activity can reduce by everyday FAS inhibitor treatment.
(Conclusion) AS metabolic disorders seem to induce colon cancer carcinogenesis, this target therapy can work for that prevention and treatment.
Citation Format: Hajime Orita, Hyeoncheol Lee, Toshiyuki Kobayashi, Tetsu Fukunaga. Chemoprevention and pharmacokinetics study using Gasdermin D knock out induced colon cancer model mouse treated with FAS inhibitors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4755.