bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4221: Association between SOX9 expression in Mexican patients with early colon cancer stage
Authors: Ruiz-Garcia Erika , Galicia Tatiana , Figueroa Edith Fernandez , Lino-Silva Saul , Lopez-Camarillo Cesar , Marchat Laurence , Calderillo German , Zinser Juan , Meneses-Garcia Abelardo , Vega Horacio Astudillo-de la 
Published: August 2018

Abstract
Introduction. Colon cancer is the fourth leading cause of mortality worldwide. Between 30-40% of patients are diagnosed at early stage (I or II), sadly 20% will relapse. It is necessary to have a biomarker that identifies patients at high risk. SOX 9 is a transcription factor required for differentiation of different cells and is important for cell proliferation, senescence and lineage commitment. The exact role of SOX9 in carcinogenesis and cancer progression is controversial because could have oncogenic and tumor-suppressing functions. Reports show that strong levels of SOX 9 in colon cancer stage II are linked to low risk of relapse. Objective. The aim of this study was to investigate if the protein expression of SOX9 was associated with the stage, clinical characteristics and relapse of Mexican colon cancer patients. Methods. We obtained 97 samples embedded in paraffin. A pathologist blinded to the clinical information determined the immunoreactivity of SOX9 into 2 groups: low and high expression (by evaluating the percentage of positive nucleus and the tissue staining intensity). All statistical analyses were conducted with SPSS v.22 Statistics. Results. We include stage I (N= 34) and stage II (N=63) patients. The median follow-up period was 42 months. We found statistical difference between SOX9 expression and age (p=0.003), tumor localization (p=0.048) and stage (p&lt0.001) for whole patients group. Twelve patients (12.3%) relapsed, 7 (at locally level) and 5 with distant metastasis: liver (N=3) and retroperitoneal nodes (N=2), all had low SOX9 expression; one patient with local relapse had died (because of surgical complications). In the relapse group, we found a significant correlation between SOX9 expression and stage (p=0.038) but not with relapse free survival (RFS). Conclusion. We found interesting data even though this is a retrospective study with limitations. This study could not associated SOX9 and RFS, because there are few events. Nevertheless, we observe that 41% patients had a systemic relapse. In the other hand, the youngest patients (&lt40 y) and the right colon had the highest SOX9 expression. With this result, we have decided to increase the sample size before any assumption, and perform NGS to the five systemic relapses.
Citation Format: Erika Ruiz-Garcia, Tatiana Galicia, Edith Fernandez Figueroa, Saul Lino-Silva, Cesar Lopez-Camarillo, Laurence Marchat, German Calderillo, Juan Zinser, Abelardo Meneses-Garcia, Horacio Astudillo-de la Vega. Association between SOX9 expression in Mexican patients with early colon cancer stage [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 4221.
Abstract 4237: Differences in the frequencies of tumor VHL mutation and HIF-2α expression between black and white patients with clear cell renal carcinoma
Authors: Callahan Catherine L. , Moore Lee E. , Lenz Petra , Schwartz Kendra , Ruterbusch Julie , Davis Faith , Chow Wong-Ho , Linehan W. Marston , Merino Maria J. , Hewitt Stephen M. , Rothman Nathaniel , Hofmann Jonathan N. , Nickerson Michael L. , Purdue Mark P. 
Published: August 2018

Abstract
Background: Black Americans have a poorer prognosis for clear cell renal cell carcinoma (ccRCC) than white Americans, potentially due in part to differences in tumor biology. In a recent analysis of The Cancer Genome Atlas (TCGA), tumors from black ccRCC patients had a lower rate of mutation in the VHL tumor suppressor gene and lower expression of hypoxia inducible factors (HIF) than tumors from white ccRCC patients. However, as this study was based on a small number of black patients (N=19) and had limited information on patients' medical histories and risk factors profiles, further investigation is needed.
Objective: We evaluated differences in the frequencies of somatic VHL gene mutations and HIF-1α and -2α protein expression between tumors from black and white ccRCC patients.
Methods: The investigation utilized formalin-fixed tissue and data collected from patients participating in a case-control study conducted in Chicago and Detroit. We sequenced VHL using the Ion Torrent platform for tumors from 69 black and 98 white patients, and measured tumor HIF-1α and -2α protein expression for 88 black and 240 white patients using immunohistochemistry.
Results: Black patients' tumors had a lower frequency of VHL mutation than those of white patients (32% vs. 49%; P = 0.03) as well as a lower frequency of above-median HIF-2α expression (33% vs. 56%; P=0.002). HIF-1α expression did not differ by race (P=0.14). These racial differences persisted after multivariable model adjustment for age, sex, hypertension, chronic kidney disease, body mass index, smoking status, stage, grade, and tumor size [VHL mutation: odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.19, 0.98; HIF-2α expression: OR = 0.33, 95% CI = 0.18, 0.61].
Conclusions: Our observation that VHL mutation and high HIF-2α expression are less frequent in ccRCC tumors of black vs. white patients confirms the earlier TCGA finding. These findings suggest that ccRCC in black patients is a fundamentally different disease than ccRCC in white patients.
Citation Format: Catherine L. Callahan, Lee E. Moore, Petra Lenz, Kendra Schwartz, Julie Ruterbusch, Faith Davis, Wong-Ho Chow, W. Marston Linehan, Maria J. Merino, Stephen M. Hewitt, Nathaniel Rothman, Jonathan N. Hofmann, Michael L. Nickerson, Mark P. Purdue. Differences in the frequencies of tumor VHL mutation and HIF-2α expression between black and white patients with clear cell renal carcinoma [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 4237.
Abstract 4239: Infection, inflammation and cancer: Understanding Alaska Native cancer health disparities
Authors: Martinson Holly , Alberts Steven , Olnes Matthew 
Published: August 2018

Abstract
Gastric cancer is a leading cancer health disparity among the Alaska Native (AN) people, occurring at a 3-fold higher incidence and 4-fold higher mortality rate in comparison to U.S. Non-Hispanic whites (NHW). AN gastric cancer patients have significant differences in tumor location and appearance compared to NHW patients. In addition, AN patients are younger at the time of diagnosis, 60 versus 69 years and have a lower 5-year survival rate of 10% compared to 22% of NHW gastric cancer patients. The purpose of this research was to understand the role of gene mutations, inflammation, and infection as possible factors in the promotion of gastric cancer in the AN population. In this study, we examined previously obtained tissue samples from AN gastric cancer patients diagnosed between 2006-2014 at the Alaska Native Medical Center. Using next-generation sequencing, immunohistochemistry and in situ hybridization, we evaluated for 50 cancer related gene mutations, the presence of the virus, Epstein-Barr virus (EBV), the bacterium, Helicobacter pylori (H. pylori), and inflammatory factors. Cancer related gene mutations were observed in 69% of gastric tumors from AN patients. The most commonly mutated genes were TP53 (30%), PIK3CA (13%), STK11 (6%), KRAS (5%), and PTEN (5%). Of particular interest, gene mutations were associated with patients who were younger at time of diagnosis (less than 55 years old) and had a history of chronic gastritis. Additionally, EBV is associated with 23% of AN gastric cancers, which is significantly higher than the 10% of EBV associated gastric cancer cases observed in other populations. EBV associated AN gastric cancer patients were more likely to have a history of chronic gastritis, prior or current H. pylori infection, and tobacco use. Notably, aberrant overexpression of the inflammatory factor cyclooxygenase 2 (COX-2) and the glycoprotein Mucin 1 (MUC1) in gastric cancer cells was significantly associated with a poorer prognosis among AN gastric cancer patients. Collectively, these findings indicate infection and inflammation are potential driving factors in the pathogenesis of gastric cancer among the AN people, which may have important clinical implications.
Citation Format: Holly Martinson, Steven Alberts, Matthew Olnes. Infection, inflammation and cancer: Understanding Alaska Native cancer health disparities [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 4239.
Abstract 425: Linked Target Capture: Rapid and high-performance NGS target enrichment for clinical sequencing applications
Authors: Pel Joel , Choi Wendy , Despotovic Milenko , Gelinas Laura , Leung Amy , Ung Lloyd , Marziali Andre 
Published: August 2018

Abstract
With the continued decrease of DNA sequencing costs, targeted next-generation sequencing (NGS) is seeing broad adoption in many research, commercial and clinical settings. However, current target capture methods typically have long, multiday workflows that can limit their clinical utility. In addition, small panels for applications such as liquid biopsy typically have high off-target rates or low uniformity, resulting in an increased cost of sequencing required to reach the desired coverage for variant detection. We have developed a novel library preparation and enrichment method named “Linked Target Capture” that replaces typical multiday "PCR-capture-PCR" workflows with a single, linked "PCR/capture" step. This approach, which uses physically linked capture probes and universal PCR primers, enables users to work from extracted DNA to loaded sequencer in less than a single day with minimal hands-on time. The linked PCR and capture step is cycled multiple times to reduce off-target DNA and increase uniformity, ultimately reducing the cost of sequencing. Additionally, the universal primers and captures probes can be combined to enable detection of DNA fusions with unknown partners. Using this method, we evaluated the ability to detect multiple mutation types from both tissue and cell free DNA, as a function of sequencing usage. Unique Molecular Identifiers (UMIs) were integrated and enabled the detection of variants below 0.1%, represented on both senses of the starting DNA (duplex sequencing). Fusion detection was also demonstrated without a priori knowledge of the fusion partner. Using a 30-gene pan-cancer panel, on-target fraction was measured to be above 95%, and the fraction of the panel covered at greater than 25% of the mean depth was greater than 99%. In summary, we have developed a method that enables rapid and cost-effective detection of clinically relevant cancer variants, such as SNVs and gene fusions. This method holds promise for many NGS areas, including clinical applications requiring rapid and simple workflows, or groups new to NGS where simple workflows and repeatable performance help remove barriers to technology adoption.
Citation Format: Joel Pel, Wendy Choi, Milenko Despotovic, Laura Gelinas, Amy Leung, Lloyd Ung, Andre Marziali. Linked Target Capture: Rapid and high-performance NGS target enrichment for clinical sequencing applications [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 425.
Abstract 4258: Magnesium intake and mortality due to liver cancer and other liver diseases: Results from the Third National Health and Nutrition Examination Survey Cohort
Authors: Xiangzhu Zhu , Wu Lijun , Fan Lei , Kabagambe Edmond K , Song Yiqing , Tao Menghua , Zhong Xiaosong , Hou Lifang , Shrubsole Martha J. , Liu Jie , Dai Qi 
Published: August 2018

Abstract
People with fatty liver disease are at high risk of magnesium deficiency. Meanwhile, low magnesium status is linked to both chronic inflammation and insulin resistance. However, no study has investigated the association between intake of magnesium and risk of mortality due to liver cancer and other liver diseases. We evaluated the association between total magnesium intake and mortality due to liver cancer and other liver diseases in the Third National Health and Nutrition Examination Study (NHANES III) cohort, which included 13,504 participants who completed liver ultrasound examination for hepatic steatosis. Overall magnesium intake was associated with a reduced risk of mortality due to liver cancer and other liver disease at borderline significance (P=0.05). In multi-variable adjusted models, every 100 mg increase in intake of magnesium was associated with a 49% reduction in the risk for mortality due to liver cancer and other liver diseases. Although interactions between magnesium intake and alcohol use and hepatic steatosis at baseline were not significant (P&gt;0.05), inverse associations between magnesium intake with liver cancer and other liver disease mortality were stronger among alcohol drinkers and those with hepatic steatosis. Our novel findings suggest higher intakes of magnesium may be associated with a reduced risk of mortality due to liver cancer and other liver disease particularly among alcohol drinkers and those with hepatic steatosis. Further studies are warranted to confirm the findings.
Citation Format: Zhu Xiangzhu, Lijun Wu, Lei Fan, Edmond K Kabagambe, Yiqing Song, Menghua Tao, Xiaosong Zhong, Lifang Hou, Martha J. Shrubsole, Jie Liu, Qi Dai. Magnesium intake and mortality due to liver cancer and other liver diseases: Results from the Third National Health and Nutrition Examination Survey Cohort [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 4258.
Abstract 4264: Mathematical modeling of differential effects of sunitinib on primary tumor and metastatic growth
Authors: Nicolò Chiara , Mastri Michalis , Tracz Amanda , Ebos John M. , Benzekry Sébastien 
Published: August 2018

Abstract
Sunitinib is a drug with anti-angiogenic activity used in the treatment of patients with metastases from renal cell carcinoma or gastrointestinal tumors. However, despite clear efficacy in reducing established tumor growth, recent preclinical studies have shown limited, or even opposing, efficacies in preventing metastatic spread.
In this work, we evaluated a mathematical metastatic model to describe primary tumor and metastatic dynamics in response to sunitinib in a clinically relevant mouse model of spontaneous metastatic breast cancer that develops after surgical removal of an orthotopically implanted primary tumor. Mice received either vehicle or sunitinib in the neoadjuvant (presurgical) setting according to different schedules. The experimental dataset comprises measurements of primary tumor kinetics, metastatic burden and pre-surgical molecular and cellular biomarkers, including vascular cell Ki67 and CD31 expression, circulating tumor cells (CTCs) and myeloid derived suppressor cells (MDSCs). Estimation of the model's parameters was performed using a mixed-effects population approach. To describe tumor growth under sunitinib treatment, a simple ordinary differential equation model of tumor growth inhibition was used.
Population fits obtained modeling the effect of treatment only on primary tumor growth described well the experimental data of all the treated groups considered. On the contrary, simulations of treatment also on metastasis could not reproduce the behavior of the data. By inserting in the model the available biomarkers as covariates, through a Wald-test, measurements of Ki67+/CD31+, CTCs and granulocytic MDSCs were found significantly correlated with the model parameter expressing the metastatic aggressiveness of the tumor.
Together, these mathematical models confirm a differential effect of sunitinib on primary (localized) tumors compared to secondary (metastatic) disease. Our results suggest that Ki67+/CD31+, CTCs and MDSCs measurements might help in predicting metastatic potential and thus aid in predicting benefit in overall survival for preoperative antiangiogenic treatments.
Citation Format: Chiara Nicolò, Michalis Mastri, Amanda Tracz, John M. Ebos, Sébastien Benzekry. Mathematical modeling of differential effects of sunitinib on primary tumor and metastatic growth [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 4264.
Abstract 4276: Analysis of sensitivity of genomic signatures of therapeutic responses of non-small cell lung cancer in patient-derived xenograft models
Authors: Tavassoly Iman , Iyengar Ravi 
Published: August 2018

Abstract
Genomic alterations are important characteristics of therapeutic responses and therapeutic-resistance phenotype in cancer. These genomic alterations are complex and are determinants of aberrations in signaling pathways and their dynamics. A genomic signature includes a set of genomic alterations like gene expressions, mutations, copy number variations, etc. These genomic signatures are used as biomarkers for assigning treatment to individuals benefiting from a specific treatment plan and are validated using preclinical models such as patient-derived xenograft models (PDX models). We have proposed a methodology to optimize these genomic signatures in silico and evaluate their accuracy in vivo using PDX models of non-small cell lung cancer (NSCLC). Our integrative analysis has shown that different sizes and complexities of gene sets provide different layers of information applicable in designing therapeutic regimens. To eliminate sloppy signatures, it is possible to find optimized and sensitive genomic signatures for precision oncology.
Citation Format: Iman Tavassoly, Ravi Iyengar. Analysis of sensitivity of genomic signatures of therapeutic responses of non-small cell lung cancer in patient-derived xenograft models [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 4276.
Abstract 4278: Somatic MAPK pathway mutations are associated with high mutational burden and good survival in head and neck squamous cell carcinoma (HNSCC)
Authors: Ngan Hoi-Lam , Fong Andrew Y. , Chan Sharon , Yu Shing Chun , Ip Laura R. H. , Grandis Jennifer R. , Lui Vivian 
Published: August 2018

Abstract
Somatic mutations of the MAPK pathway occur in ~14% of head and neck squamous cell carcinoma (HNSCC; TCGA Provisional; www.cbioportal.org). Notably, mutations found in MAPK signaling components are apparent hotspot or activating mutations, potentially driving activation of the MAPK pathway. These mutations include HRAS p.G12V/D/A/C/S & p.G13V/R, MAPK1 p.E322K/*, BRAF p.D594N & p.V600E mutations. We found that this MAPK pathway mutated subset of HNSCC tumors have a higher mutational burden than MAPK-wildtype (WT) tumors. The average rate of non-synonymous mutations in MAPK pathway mutated tumors is 265.1±42.84 mutation/tumor vs 143.5±5.83 mutation/tumor in WT tumors in the TCGA cohort (P=0.0005). MAPK pathway mutations are not associated with HPV positivity (P=0.5815). Subsequent analysis shows that this subset of MAPK pathway-mutated tumors is unexpectedly associated with TP53 wildtype status (P=0.005584), as well as CASP8 mutations [29.3%; 27/92 cases vs. a 6.5% rate (27/418 cases) in the MAPK pathway WT group; P=9.91 x10-9]. Based on the current survival data of the TCGA Provisional cohort, it appears that patients whose tumors bearing HRAS, BRAF, MAPK1, MAP2K1, and RPS6KA1 mutations have a long median survival of 7.94 years (95.3 months; P=0.0165) vs. patients without these somatic mutations. Though TP53 WT status is a well-recognized biomarker for good prognosis in HNSCC, it only predicts with a median survival of ~45.8 months in this very same cohort. Thus, our findings suggest that MAPK pathway mutations may serve as potential genomic biomarkers for good prognosis in HNSCC. Recently, both HRAS and MAPK1 hotspot mutations have been shown to serve as potential neo-antigens in cervical cancer. Further investigation is needed to determine if these somatic MAPK pathway mutations are capable of mounting an anti-cancer immunity (via hotspot neo-antigens or neo-antigens due to higher mutational burden per se) in these patients, which may contribute to their improved survival. Acknowledgements: VWYL received funding supports from the Research Grant Council, Hong Kong (General Research Fund: #1711484, #17121616; Theme-based Research: T12-401/13-R) and the Hong Kong Cancer Fund, Hong Kong.
Citation Format: Hoi-Lam Ngan, Andrew Y. Fong, Sharon Chan, Shing Chun Yu, Laura R. H. Ip, Jennifer R. Grandis, Vivian Lui. Somatic MAPK pathway mutations are associated with high mutational burden and good survival in head and neck squamous cell carcinoma (HNSCC) [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 4278.
Abstract 4281: A family-wide computational analysis of the catalytic domains of the Never In Mitosis A-like kinase (NEK) proteins
Authors: Durmus Carline A. , Singh Shaneen 
Published: August 2018

Abstract
Members of the Never In Mitosis A-like kinase (NEK) proteins are overexpressed in leukemia, breast, ovarian, prostate, and cervical cancers. Overexpression of particular NEK proteins is also implicated in the increased resistance of certain cancer cells to premature senescence due to various cancer treatments. Depending on the cancer cell type, there are NEK members that, when inhibited, either increase the cancer cells' susceptibility to specific drugs or increase their resistance. Structural information and model of action of NEKs is limited to only two members of the family, even though the different members play an important role in human metabolism. The goal of this research is to perform a comprehensive computational analysis of the 11 members of the human NEK protein family. To provide detailed annotations of the NEK family members, the three-dimensional structures of the catalytic domains was modeled using various approaches including template-based modeling, threading, and ab inito techniques. The information gathered from the models was integrated with information obtained from sequence analysis, biophysical characterization including surface electrostatic profiles, and predicted molecular interactions involving NEK members and other proteins/ macromolecules to establish structure-function correlations. Here we present a detailed analysis of the catalytic domains of the 11 NEK proteins and propose interaction and binding partners for each of the individual members of the family. The role of NEKs in the cell cycle, numerous medical disorders, and as potential chemotherapeutic targets underscores the importance of understanding the structure-function relationship of this family of proteins and establishing their mechanism of action, including delineating the differences among the different members of the family, and our study is a step in that direction.
Citation Format: Carline A. Durmus, Shaneen Singh. A family-wide computational analysis of the catalytic domains of the Never In Mitosis A-like kinase (NEK) proteins [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 4281.