bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 171: Comparative genomic analyses of synchronous colorectal cancers by exome sequencing
Authors: Hänninen Ulrika A. , Tanskanen Tomas , Katainen Riku , Böhm Jan , Taipale Minna , Taipale Jussi , Mecklin Jukka-Pekka , Mäkinen Netta , Aaltonen Lauri A. 
Published: July 2016

Abstract
Colorectal cancer (CRC) is the third most common cancer type and the second leading cause for cancer deaths in the Western world. Around 3.5% of CRC patients have more than one primary colorectal carcinoma at the time of diagnosis. These so-called synchronous colorectal cancers (SCRC) are more common in men and have been associated with predisposing conditions, such as hereditary nonpolyposis colorectal cancer (HNPCC), familial adenomatosis polyposis (FAP) and inflammatory bowel disease. Such conditions account for slightly more than 10% of SCRC cases. The pathological and clinical features of the tumors have been widely studied. The underlying molecular mechanisms in SCRC have not been well described, though. The research has mainly focused on single factors such as microsatellite instability (MSI) status or APC-, KRAS-, and p53-mutations.
By exome sequencing a tumor pair and corresponding normal sample from 23 patients, we aim to study the extent of genetic overlap between the synchronous tumors to assess if they derive from a common progenitor. The tumor data will be filtered against the normal tissue data to verify the somatic origin of the observed mutations. The comparison of the mutation profiles in each tumor pair will take into account the number of shared variants that occur in the exact same positions in the coding region. If the tumors share a high number of changes in exactly the same base it would suggest they have a common origin. Different mutation patterns, with possibly a few coincidental shared mutations, may support a stochastic process in the genesis of the two tumors. We will also identify commonly mutated genes - those that are mutated in both tumors of a synchronous pair or among synchronous pairs of different patients.
The patient material derives mainly from a consecutive, population-based colorectal cancer collection “Suolisyöpä Keski-Suomi 2000-2010” from Jyväskylä, Finland. In addition three SCRC-cases were included from our in-house collections. Knowledge on the molecular basis of SCRC, which haven't been studied to this extent before, provides insight on how these tumors arise and allows for development of more personalized treatments.
Citation Format: Ulrika A. Hänninen, Tomas Tanskanen, Riku Katainen, Jan Böhm, Minna Taipale, Jussi Taipale, Jukka-Pekka Mecklin, Netta Mäkinen, Lauri A. Aaltonen. Comparative genomic analyses of synchronous colorectal cancers by exome sequencing. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 171.
Abstract 1710: Novel syngeneic mouse gastric cancer models identified Sca-1 as a gastric cancer stem cell marker
Authors: Park Jun Won , Kim Hark K. 
Published: July 2016

Abstract
Genetically well-defined syngeneic mouse models for gastric cancer are not available in the scientific community, but critical for the development of immunotherapeutic agents. We generated primary mouse gastric cancer cell line NCC-S1 (S1) established from a Villin-cre;Smad4F/F;Trp53F/F;Cdh1F/wt mouse and its metastatic variant cell line NCC-S1M (S1M). These cells closely recapitulated human diffuse type gastric cancers in histology and molecular profiles. S1M cells showed enhanced in vivo growth and metastatic potentials compared with S1 cells, and developed orthotopic and heterotopic tumors in immunocompetent mice in predictable manner. S1M allograft model was useful for testing the efficacy of an immunotherapeutic agent, anti-4-1BB. Sca-1 was overexpressed in S1M cells compared with S1 cells. Approximately 7% of gastric cancer cells in primary tumors expressed Sca-1. Sca-1high cells were more tumorigenic according to the in vivo limiting dilution assay, and more resistant to cisplatin and fluorouracil. Sca-1high cells overexpressed CD133, CD44, EPCAM and Bcl-xL. A chromatin immunoprecipitation analysis demonstrated that Sca-1 was a β-catenin/LEF1 target gene. Expression profiles of 85 genes overexpressed in Sca-1high S1 cells clustered 123 pretreatment gastric cancer patient samples according to the overall survival following cisplatin/fluorouracil chemotherapy. Thus, our novel metastatic gastric cancer cell lines are useful resources for drug development, and identified Sca-1 as a novel gastric cancer stem cell marker that mediates β-catenin signaling.
Citation Format: Jun Won Park, Hark K. Kim. Novel syngeneic mouse gastric cancer models identified Sca-1 as a gastric cancer stem cell marker. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1710.
Abstract 1717: Circulating tumor cells from in vitro 3D culture systems have tumor-initiating capacity in vivo
Authors: Cabrera Marina C. , Hurt Elaine , Chen Xiaoru , Xiaoqing Shi , Bao Haifeng 
Published: July 2016

Abstract
Circulating tumor cells (CTCs) are cells that have detached from the primary tumor and entered the bloodstream with the potential to seed metastatic tumors in distal sites. High CTC numbers correlate with aggressive disease, increased metastasis, and decreased time to relapse. It has also been shown that cancer stem cells (CSCs) represent a proportion of the CTCs present in patients. Given that CSCs are resistant to chemotherapy and are responsible for tumor initiation, it is posited that the CSCs are the seeds of metastasis. However, direct evidence for this hypothesis is limited because there are few methods for culturing and studying these rare cells. We are using a 3D culture chamber system (RealBio D4™) to establish long-term cultures of human-derived breast and pancreatic tumors. We observed that the system's 3D matrix supported culture development and incorporation of tissue organization and microenvironment. Further, the chamber design allowed CTCs generated within the cultures to migrate out of the cell mass into the circulating nutrient medium where they were collected for characterization. The isolated CTCs displayed CSC properties via CellSearch® (CD44+,CD24-; CD44+,CD24+ for breast and pancreas respectively). In addition, these isolated CTCs displayed tumor-initiating capacity when implanted into mice. Future studies will compare CTCs isolated from 3D culture with cells from tumors, blood, and tissue grown on scaffold through RT-PCR, histology, and gene expression assays.
Citation Format: Marina C. Cabrera, Elaine Hurt, Xiaoru Chen, Shi Xiaoqing, Haifeng Bao. Circulating tumor cells from in vitro 3D culture systems have tumor-initiating capacity in vivo. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1717.
Abstract 172: Managing metastatic breast cancer via serial monitoring with circulating cell-free tumor DNA next generation sequencing testing
Authors: Austin Laura , Nagy Rebecca , Zill Oliver , Lanman Richard B. , Talasaz AmirAli , Cristofanilli Massimo 
Published: July 2016

Abstract
Background: Metastatic breast cancer (MBC) is an incurable disease with complex molecular features including somatic mutations that evolve in relation to genomic instability and selective treatment pressure. Patients with treatment-refractory MBC may benefit from tumor genomic evaluation using next generation sequencing (NGS). Furthermore, analysis of circulating tumor DNA (ctDNA) in patients with advanced disease offers the possibility of non-invasive molecular monitoring.
Methods: A patient with MBC was tested at each progression with a ctDNA NGS panel (Guardant360™) that includes all NCCN-recommended somatic genomic variants for solid tumors and sequences complete exons of &gt;50 genes to report single nucleotide variants (SNVs), fusions, amplifications, and indels with high sensitivity and ultra-high specificity (&gt;99.9999%). The patient was diagnosed with invasive breast cancer at age 44 and treated with surgery and hormonal therapy. At age 61, she had axillary adenopathy and liver metastases. Treatment details are in Table 1.
Results: ctDNA analysis was performed at the time of metastatic diagnosis and at 5 additional time points over the course of treatment. All samples revealed an ERBB2 exon 19 indel (p.Leu755_Glu757delinsSer), and multiple SNVs and gene amplifications. ERBB2 amplification was seen in 4 of 6 samples. Mutant allele fractions (Table 1) correlated with clinical response to treatment and progression.
Conclusions: Analysis of ctDNA in this patient identified an ERBB2 exon 19 indel, which are present in 2-4% of non-small cell lung cancers but 1-2% in breast cancer. Treatment with anti-HER2 monoclonal antibody or dual anti-EGFR/ERBB2 tyrosine kinase inhibitor therapies may show clinical benefit. ctDNA analysis can detect emergence of actionable resistance mutations with the advantage of serial evaluation, allowing capture of inter- and intra-tumor heterogeneity and illustration of molecular progression and response. Table 1.Blood DrawDisease status at time of blood drawMutant allele fraction of ERBB2 indel (* = ERBB2 amplification)Treatment1Initial diagnosis9%trastuzumab, pertuzumab and docetaxel (TPD), cycle 12Stable disease1%*TPD cycle 23Progressing10%*TPD cycle 34Progressing62%*trastuzumab, emtansine (TDM1) 3 cycles5Progressing70%*vinorelbine, trastuzumab, everolimus6Partial response1%flourouracil, epirubicin, cyclophoasphamide
Citation Format: Laura Austin, Rebecca Nagy, Oliver Zill, Richard B. Lanman, AmirAli Talasaz, Massimo Cristofanilli. Managing metastatic breast cancer via serial monitoring with circulating cell-free tumor DNA next generation sequencing testing. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 172.
Abstract 1729: Withaferin A blocks formation of IFN-γ-induced metastatic cancer stem cells through inhibition of the CXCR4/CXCL12 pathway in the UP-LN1 carcinoma cell model
Authors: Chou Andy Shau-Bin , Ting Li-Lei , Hsieh Chin-Hsuan , Pang See-Tong , Liao Shuen-Kuei 
Published: July 2016

Abstract
As our understanding of cancer stem cell (CSC) biology improves, there is an urgent need to search for inhibitory agents of CSCs and metastatic CSCs (mCSCs) positive for CXCR4. Withaferin A (WA), a withanolide extracted from the medicinal plant Withania somnifera, has been shown to exhibit anti-cancer effects through multiple mechanisms. Whether WA could selectively target CSCs, mCSCs, or non-CSCs of a gastrointestinal (GI) carcinoma tumor remains unclear. Side population analysis, flow cytometric phenotyping and sorting, non-invasive imaging in conjunction with xenotransplantation, and immunohistology were used in this investigation. Using the lymph node metastatic GI cancer cell line UP-LN1, consisting of CD44high/CD24low grape-like floating (F) and CD44low/CD24high adherent (A) cell subsets, this study demonstrated that, as compared with parental UP-LN1 cells or A cells, WA preferentially reduced F-cell proliferation, tumor sphere formation, and side population cells in vitro in greater efficiencies by apoptosis. This action was mechanistically mediated via the down-regulation of CXCR4/CXCL12 and STAT3/IL-6 pathways, both of which are instrumental in the acquisition of metastatic ability. Attenuation of IFN-γ-induced CXCR4 expression in F cells by knockdown with siRNA or blocking with anti-CXCR4 antibody, followed by Western blot analysis, showed significantly reduced metastatic potential in vitro. The extent of in vitro anti-invasive effect of WA on the IFN-γ-treated F cells was significantly greater than on the F cells without WA treatment, or F cells treated with control siRNA or with control IgG antibody. The observed in vitro effects of WA on the CSC and mCSC targeting were validated by data obtained with non-invasive imaging in NOD/SCID mouse xenotransplantation. We conclude that WA could efficiently block the formation of both CSCs and mCSCs in the UP-LN1 cell line, suggesting that WA may be considered an effective therapeutic agent for GI malignancies exhibiting grape-like tumor sphere.
Citation Format: Andy Shau-Bin Chou, Li-Lei Ting, Chin-Hsuan Hsieh, See-Tong Pang, Shuen-Kuei Liao. Withaferin A blocks formation of IFN-γ-induced metastatic cancer stem cells through inhibition of the CXCR4/CXCL12 pathway in the UP-LN1 carcinoma cell model. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1729.
Abstract 1748: The relationship between nut consumption and risk of colorectal cancer
Authors: Lee Jeeyoo , Shin Aesun , Lee Jeonghee , Park Ji Won , Oh Jae Hwan , Kim Jeongseon 
Published: July 2016

Abstract
Introduction
Nuts consumption has been associated with reduced risk of obesity, diabetes mellitus, and cardiovascular diseases. However, the association between nuts and colorectal cancer risk remains unclear.
Objective
In this study, we aimed to investigate the relationship between nuts consumption and colorectal cancer risk in a case-control study.
Methods
A case-control study was conducted with 923 colorectal cancer patients and 1846 controls recruited from the National Cancer Center in Korea. Information on dietary intake was collected using a food frequency questionnaire (FFQ) with 106 items. Nuts consumption level was classified by sex-specific quartile of control group. Binary and polytomous logistic regression models were used to estimate odds ratios (OR) and their 95% confidence intervals (CI) for the association between nuts consumption and colorectal cancer risk.
Results
High nuts consumption was strongly associated with a reduced risk of colorectal cancer in women (OR, 0.18; 95% CI 0.10-0.32 for highest vs. lowest quartile) and similar inverse association was observed for men (OR, 0.36; 95% CI 0.25-0.52). In subsite analysis, adjusted ORs (95% (CI)) comparing the highest vs the lowest quartile of nuts consumption were: 0.49 (0.24-0.99) for proximal colon cancer, 0.38 (0.23-0.64) for distal colon cancer, and 0.29 (0.18-0.46) for rectal cancer in men. An inverse association was also found in women for proximal colon cancer (0.16 (0.05-0.51)), distal colon cancer (0.16 (0.07-0.37)) and rectal cancer (0.25 (0.12-0.51)).
Conclusion
We found a statistically significant association between higher nuts intake and reduced risk of colorectal cancer and the association was observed for all subsites of colorectum in both men and women.
Citation Format: Jeeyoo Lee, Aesun Shin, Jeonghee Lee, Ji Won Park, Jae Hwan Oh, Jeongseon Kim. The relationship between nut consumption and risk of colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1748.
Abstract 1763: Body size and incidence of TMPRSS2:ERG fusion-positive and fusion-negative prostate cancer
Authors: Ahearn Thomas , Graff Rebecca E. , Pettersson Andreas , Pernar Claire , Markt Sarah C. , Wilson Kathryn M. , Fiorentino Michelangelo , Loda Massimo , Giovannucci Edward L. , Mucci Lorelei A. 
Published: July 2016

Abstract
Background: Evidence suggests that genetic, lifestyle, and hormonal factors are differentially associated with the incidence of TMPRSS2:ERG fusion-positive and fusion-negative tumors, suggesting that these molecular subtypes have distinct etiologies. There is scant literature on whether anthropometrics are differentially associated the risk of developing fusion-positive and fusion-negative prostate cancer.
Methods: We examined the associations between adult height, recalled BMI at age 21, and updating BMI over time with risk of prostate cancer defined by TMPRSS2:ERG subtype using a prospective cohort of 49,372 men from the Health Professionals Follow-up Study. Tumor TMPRSS2:ERG status was assessed by ERG immunohistochemistry on tissue microarrays constructed from radical prostatectomy of the prostate specimens. We utilized multivariable competing risks models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of fusion-positive disease and, separately, fusion-negative disease.
Results: During 23 years of follow-up, we identified 5,847 total prostate cancer cases. Among them, 2,402 were treated with RP, of whom 913 (15.6% of all cases) were assayed for ERG status. Height (per 5 inches) was positively associated with the risk of developing ERG-positive prostate cancer (HR = 1.24, 95% CI 1.03-1.50), but not associated with ERG-negative disease (HR = 0.98, 95% CI = 0.82-1.18, Pheterogenity = 0.07). Updated BMI (per 5 kg/m2) was inversely associated with the risk of developing ERG-positive disease (HR = 0.86, 95% CI = 0.74-1.00), but not associated with ERG-negative disease (HR = 1.03, 95% CI = 0.90-1.18, Pheterogenity = 0.07). BMI at age 21 was not differentially associated with the risk of developing ERG-positive or ERG-negative disease.
Conclusion: Our results suggest that height and obesity are differentially associated with the risk of developing fusion-positive and fusion-negative prostate cancer.
Citation Format: Thomas Ahearn, Rebecca E. Graff, Andreas Pettersson, Claire Pernar, Sarah C. Markt, Kathryn M. Wilson, Michelangelo Fiorentino, Massimo Loda, Edward L. Giovannucci, Lorelei A. Mucci. Body size and incidence of TMPRSS2:ERG fusion-positive and fusion-negative prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1763.
Abstract 1775: Differential expression of exosomes-associated onco-microRNAs in African Americans with prostate cancer
Authors: Moustafa Ahmed A. , Sholl Andrew B. , Tsumagari Koji , Hassan Mohamed , Kandil Emad , Abdel-Mageed Asim B. , Abd Elmageed Zakaria Y. 
Published: July 2016

Abstract
Background: The mortality rate of prostate cancer (PCa) is two times higher in African American (AA) than Caucasian American (CA) men. The molecular mechanisms underlying these health disparities among AA men have yet to be fully elucidated. Our study aimed to evaluate the role of exosomes-associated onco-microRNAs (miRs) as biological determinant for the racial disparity of PCa patients.
Methods: Exosomes were isolated from the conditioned medium of MDA-PCa-2b (AA-origin), PC-3 (CA origin), C4-2B and RWPE-1 (non-tumorigenic) cell lines to study the endogenous expression of a number of onco-miRs and their anticipated target genes using Real-Time PCR and Western blot analyses. The potential candidates were validated in exosomes procured from plasma of human AA PCa patients and their counterparts. Onco-miRs target genes such as Lats-2, PDCD4, and SMEK1 were validated on cellular and exosomes derived from cells and human specimens. Onco-miRs and their targets were correlated with age and Gleason score of the disease.
Results: Not only onco-miR-125b, miR-155, and miR-3613 were upregulated in PCa versus normal RWPE1 cells but also in AA versus CA PCa cells. Onc-miR-3613 and miR-3680 were 3-4 times upregulated in cells and in C4-2B-derived exosomes compared to RWPE-1-derived vesicles. Also, these miRs were upregulated (∼2.5 fold) in MDA-PCa-2b versus PC-3 cells. The expression of tumor suppressor genes, such as Lats2, PDCD4, and SMEK1, were downregulated in PCa cells compared to normal cells. Differential expression of PCa exosomes-associated onco-miRs was also demonstrated in AA PCa patients compared to CA PCa and their age-matched normal subjects. A positive correlation was found between onco-miR-125b and high Gleason score (r = 0.763, p&lt;0.01).
Conclusion: Our findings underline the role of exosomes-associated onco-miRs in health disparity of PCa. The differential expression of onco-miRs and their tumor suppressor genes in AA men projects their potential role as prognostic markers and/or future therapeutic targets in the context of racial disparity.
Citation Format: Ahmed A. Moustafa, Andrew B. Sholl, Koji Tsumagari, Mohamed Hassan, Emad Kandil, Asim B. Abdel-Mageed, Zakaria Y. Abd Elmageed. Differential expression of exosomes-associated onco-microRNAs in African Americans with prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1775.
Abstract 1781: Ethnic disparity in pediatric leukemia relapse
Authors: Gillespie Mirinda , Hale Greg , Amankwah Ernest K. 
Published: July 2016

Abstract
Background: Leukemia is the most prevalent pediatric malignancy, representing 25% of all cancer diagnoses among children. Despite recent substantial improvements in therapy that have dramatically increased survival, 10-20% of cases develop relapse and become refractory to treatment. Although racial/ethnic disparity in survival is well documented, limited knowledge currently exists on the disparity in relapse. The objective of this study was to compare the risk of pediatric leukemia relapse between Hispanic Whites and non-Hispanic Whites.
Methods: The study included children (&lt;21 years) diagnosed with leukemia between January 2006 and December 2014 at the All Children's Hospital Johns Hopkins Medicine, St. Petersburg, FL. Patients’ demographic and clinical information were obtained from an electronic health record-derived data warehouse. Ethnicity was self-reported. Leukemia diagnosis and relapse were identified using appropriate ICD-9 codes. Relapse-free survival was defined as the time from diagnosis to the first documentation of relapse. Hazard ratios (HR) and 95% confidence intervals (95% CI) for relapse-free survival were calculated using Cox proportional hazard models adjusting for age at diagnosis, gender and type of insurance (commercial vs government).
Results: The study included 66 Hispanic Whites and 202 non-Hispanic Whites. The median age for both groups was 7 years. However compared to non-Hispanic Whites, Hispanic Whites were more likely to be males (59% vs 53%), to have government insurance (71% vs 35%) and had a shorter median follow up time (52 vs 66 months). Approximately 15% of Hispanic Whites developed relapse compared to only 5% non-Hispanic Whites. Kaplan-Meier survival analysis showed a difference in relapse between the two groups (log-rank p = 0.006). After adjusting for age at diagnosis, gender and type of insurance, Hispanic Whites were three times more likely to develop relapse compared to non-Hispanic Whites (HR = 3.1, 95%CI = 1.2-8.0, p = 0.02).
Conclusion: Although the findings of this study suggest that ethnic disparity in pediatric leukemia may exist, our findings are limited by the inability to control for potential confounders such as medication adherence, timing of diagnosis, white blood cells at diagnosis and minimal residual disease. Future studies should further investigate this racial/ethnic disparity.
Citation Format: Mirinda Gillespie, Greg Hale, Ernest K. Amankwah. Ethnic disparity in pediatric leukemia relapse. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1781.