bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B23: Detection of susceptibility to childhood Acute Lymphoblastic Leukemia (ALL)
Authors: Tebbi Cameron K. 
Published: May 2019

Abstract
Currently, there are no known methods to predict of susceptibility to, and means for prevent Acute Lymphoblastic Leukemia (ALL). We have evaluated and patented a group of proteins dubbed Protein X from a certain strain of Aspergillus Flavus (AF) and developed methods for screening and identifying totally asymptomatic patients in remission of ALL, including long term survivors of this disease, distinguishing them from normal controls. Subject to institutional approved consents/assents, 15-20 ml of blood was obtained from 40 cases of ALL in children and young adults, including long term survivors of ALL. Controls were normal individuals, sickle cell patients undergoing partial exchange transfusion and patients with solid tumors. Mononuclear leukocytes (MNL) of ALL patients in remission and controls were separated using Ficoll Paque Plus (GE Healthcare). Epstein Barr virus (EBV) was obtained commercially. Positive and negative controls for Protein X were aflatoxin and Mycocladus Corymbifera (MC). Avian leukosis virus (ALV) was used as control for EBV. MNL were co-incubated with Protein X ± EBV ± irradiation, for periods of 1-72 hours. Controls were treated identically with appropriate substitutions. Test and control MNLs were examined for genetic markers, NF-κB and cell surface markers (CSM) including CD10/CD19, CD34/CD19, and CD34/CD117. Changes were expressed as percentage of control. Using ELISA, plasmas were tested for antibodies against Protein X ± EBV time experiments reveled 72 hours was optimum for achieving results. Upon 72 hours exposure of MNL from ALL to Protein X ± EBV, cells from ALL patents in remission developed cell surface phenotypes typical of ALL. This was not seen in controls. Addition of EBV ± radiation to Protein X, enhanced these effects in MNL of ALL and not controls. Changes were statistically significant and clearly separated ALL from controls. Evaluation of NF-κB revealed enhancement in ALL and not controls. Aflatoxin indiscriminately induced cell surface marker changes in both, normal and ALL, while ALV and supernatant of MC had no effect. ELISA, using Protein X ± EBV, distinguished ALL from controls. Gene array and biomarkers confirmed transformation to leukemic cell markers upon exposure to Protein X in cells from ALL patients but not controls. These studies reveal, in vitro, upon exposure to Protein X, unlike normal controls, MNL from ALL patients in remission develop cell surface phenotypes and genetic markers typical of ALL. These techniques have potential for screening for ALL and may have implications for etiology of ALL and its prevention.
Citation Format: Cameron K. Tebbi. Detection of susceptibility to childhood Acute Lymphoblastic Leukemia (ALL). [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr B23.
Abstract IA10: Targeted imaging of the serrated pathway for early detection of colorectal cancer
Authors: Wang Thomas D. 
Published: May 2019

Abstract
Background and Significance: Colorectal cancer (CRC) is a leading cause of cancer-related mortality with ~1.4 million new cases diagnosed globally and ~690,000 annual deaths. The serrated pathway is a primary cause of CRC in the proximal colon. Sessile serrated adenomas (SSA) have flat and subtle features that are difficult to detect with conventional white light colonoscopy.
Aims: We aim to identify a peptide imaging agent that binds specifically to SSA to improve visualization of pre-malignant lesions in the proximal colon.
Methods: We used phage display technology with subtractive biopanning against cells with a V600E point mutation in BRAF. We performed a first-in-humans clinical study by topically administering this FITC-labeled peptide in the proximal colon of n = 38 human subjects, and performed in vivo imaging using a wide-field endoscope that is sensitive to fluorescence.
Results: We identified the peptide sequence KCCFPAQ, and measured an apparent dissociation constant of kd = 72 nM and an apparent association time constant of kd = 0.174 min-1 (5.76 min). On in vivo fluorescence images, we measured a 2.43-fold greater target-to-background ratio for SSA than for normal colonic mucosa, and could distinguish SSA with 89% sensitivity and 92% specificity. We found 84% sensitivity and 91% specificity for discriminating SSA from traditional adenomas. No toxicity was attributed to the peptide in either animal or patient studies. On ex vivo images, we found the mean fluorescence intensity for SSA to be significantly greater than that for hyperplastic polyps.
Conclusions: We have identified a fluorescently-labeled peptide that is safe for clinical use, and is specific for detecting SSAs in the proximal colon with wide-field imaging. This targeted imaging methodology may be useful for early detection of pre-malignant serrated lesions on routine colonoscopy.
Citation Format: Thomas D. Wang. Targeted imaging of the serrated pathway for early detection of colorectal cancer. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr IA10.
Abstract IA12: Risk-assessment in HPV-based cervical cancer screening
Authors: Herrero Rolando 
Published: May 2019

Abstract
Cervical cancer screening is rapidly evolving to incorporate highly accurate molecular methods that are able to categorize women's risk of cervical cancer and allow recommendations for follow-up or treatment. HPV nucleic acid testing provides highly sensitive and reproducible detection of HPV infection, a necessary cause of cervical cancer. Thus, virtually all women who have a cervical cancer precursor or who will develop one in the following years are HPV positive. On the other hand, the vast majority of HPV positive women have transient infections that will disappear in a few months. In this context, further evaluation of HPV positive women using triage methods allows further risk stratification that avoids unnecessary evaluations and overtreatment. Women positive for the triage test are referred for immediate colposcopic evaluation and follow-up (or, in some contexts, immediate treatment) as needed, while those who test negative usually receive another screening test in a year (or more). Triage with cytology or co-testing with HPV and cytology selects a group at clearly higher risk and generally above the recommended threshold for immediate colposcopy referral based on current consensus guidelines. For HPV positive women, genotyping for HPV 16 and 18 allows further risk stratification, but the additional benefit of other HPV genotypes is unclear. Ideally, triage methods are performed on the same specimen where the HPV test was carried out, to avoid additional visits. Risk stratification is different in different populations and age groups as HPV prevalence and type distribution, as well as screening histories are highly variable around the world. The programmatic decisions need to take into account the feasibility and logistics of different approaches and their respective burden on health services. Further research, particularly in low and middle income countries and in vaccinated cohorts is required.
Citation Format: Rolando Herrero. Risk-assessment in HPV-based cervical cancer screening. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr IA12.
Abstract IA21: Translating evidence to action: Yourdiseaserisk.wustl.edu
Authors: Colditz Graham A. 
Published: May 2019

Abstract
Not very long ago scientific publication was viewed as the primary dissemination goal of scientific discovery. This viewpoint, however, has evolved substantially over the past 10 - 20 years. While scientific discovery and publication remain key to dissemination of findings, it is now often viewed as a single stage in the spectrum from discovery to the application of research results. The view of effective dissemination must now also include the practical world of policy makers, clinicians, health care organizations, and the public – groups that need good data and good tools to make informed decisions that drive individual, national, and global health. The development of health risk assessment and prevention tools can play a key role in doing this. And such development moves through three general translation stages – with each subsequent stage marked by greater difficulty to achieve. 1) Creation of accurate risk prediction calculation(s) from current evidence base. 2) Development of a practical, usable tool that incorporates the calculation(s) and provides actionable messages – for clinical, public policy, or public use. 3) Integration of risk prediction tools with the social, structural, and financial support for translating recommended action messages into actual action – whether we're talking about doctors counseling patients, government representatives making health policy, or the public working to improve their own health. This process by necessity requires a multi-disciplinary approach – drawing on expertise from epidemiology, biostatistics, communication theory, coding, and design – among others. With the addition of precision medicine and big data to long-established data analysis techniques, the field of risk prediction is set to expand in coming years. Along with that expansion, it is important to assure that our efforts are valid, useful, reliable, and applicable.
Citation Format: Graham A. Colditz. Translating evidence to action: Yourdiseaserisk.wustl.edu. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr IA21.
Abstract IA22: Using risk assessment tools to motivate behavior change
Authors: Waters Erika A. 
Published: May 2019

Abstract
Epidemiology identifies risk factors for cancer and other diseases based on the idea that conveying such information to healthcare providers, the general public, and policy makers will result in population-wide improvements in healthy behaviors and, consequently, population-wide improvements in health outcomes. These actions assume that the audience understands and uses the information to make health-related decisions. However, the language of epidemiology, which is steeped in probabilistic thinking, is not necessarily the language of the general public. Furthermore, growing evidence suggests that the language of epidemiology is not particularly well-understood by policy makers or even, disconcertingly, by some healthcare providers.
This presentation will accomplish three objectives. First, it will demonstrate how a user-friendly, Internet-based, personalized risk assessment tool that uses established principles of risk communication and is grounded in health behavior change theories can increase motivation to change behavior. It will accomplish this in the context of using Your Disease Risk to inform women about the association between physical activity and breast cancer risk.
Second, it will illustrate the development of a novel personalized risk assessment tool that increases understanding of the link between lifestyle behaviors and overall health and wellness. Specifically, it translates cumulative incidence data about five diseases that cause significant morbidity and mortality (i.e., colon cancer, breast cancer (women), heart disease, diabetes, and stroke) into a tool that conveys personalized risk estimates in a comprehensible and useful way for laypeople from diverse socio-demographic backgrounds. The premise is that illustrating how a single behavior can affect the likelihood of developing several diseases could foster a more coherent and meaningful picture of the behavior's importance in reducing health risks and could increase motivation to engage in the behavior. The behavioral context for this study is also physical activity.
Third, this presentation discuss the limits of tools that convey only risk information and do not help users bridge the gap between wanting to change their behavior and having the knowledge, skills, and confidence to actually initiate and maintain such changes.
Citation Format: Erika A. Waters. Using risk assessment tools to motivate behavior change. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr IA22.
Abstract IA25: Implementation of risk prediction to improve health: The promises and challenges of precision
Authors: Kramer Barnett S. 
Published: May 2019

Abstract
Advances in the understanding of risk factors have transformed oncology, providing leads for prevention and, in particular, screening. Part of this transformation has been fueled by studies of molecular changes and genetic mutations that are inherited or that precede cancer by years, potentially leading the way to a new era of precision screening and prevention. However, these new leads bring important challenges that demand caution. As Sean Carroll has pointed out, it turns out that life from the molecular scale all the way up to the ecological scale is usually governed by longer chains of interactions than we first imagine, with more links in between (Serengeti Rules: The Quest to Discover How Life Works and Why It Matters, 2016).
Rather than screening for existing asymptomatic disease, we have entered the era of screening for risk factors, or even screening for risk factors for risk factors (disease risk predisposition). This is a double-edged endeavor, because genes may influence fate, but not in a linear or straightforward manner. Therefore, prediction of outcome is far less precise than measurement of the predisposing genetic and molecular alterations. Many people may be labeled as carriers of risk factors that will never develop the clinical forms of the disease predicted by the genetic changes, a form of genetic overdiagnosis. So the new era of risk prediction can bring both benefits and harms. A critical tool in determining the balance of benefits and harms of increasingly sensitive omics technologies is the use of a formal analytic framework, to be discussed in the presentation.
Citation Format: Barnett S. Kramer. Implementation of risk prediction to improve health: The promises and challenges of precision. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr IA25.
Abstract PR09: Prostate cancer prognostication based on an actionable metabolic pathway
Authors: Stopsack Konrad H. , Gerke Travis A. , Mucci Lorelei A. , Rider Jennifer R. 
Published: May 2019

Abstract
Background: We recently discovered that mRNA expression of SQLE, coding for squalene monooxygenase, the second rate-limiting enzyme of cholesterol synthesis, is associated with lethality after prostate cancer diagnosis. Here, we investigate how expression of SQLE and other key regulators of cholesterol homeostasis, identified by prior mechanistic studies, aid risk prediction for lethal prostate cancer.
Methods: The Health Professionals Follow-up Study and the Physicians' Health Study prostate cancer tissue cohorts collected tissue from prostatectomy or transurethral resection of the prostate at cancer diagnosis. Whole-transcriptome profiling was performed. The outcome of interest was lethal cancer defined as prostate cancer mortality or development of metastases in contrast to non-lethal cancer without evidence of metastases after at least eight years of follow up. Discrimination for prostate lethal cancer was assessed by comparing c-statistics using bootstrap resampling.
Results: Combining both cohorts, 112 men had lethal prostate cancer; 290 men had non-lethal cancer. A prognostic model for lethal cancer including Gleason grade, pathologic stage, age, and year of diagnosis had a high c = 0.885; adding body mass index, smoking status, family history of prostate cancer, and diabetes diagnosis increased c to 0.889. A model containing only SQLE (linear) achieved c = 0.663. Adding SQLE to the fully adjusted model increased c to 0.903 (p = 0.027). None of the other cholesterol regulators ABCA1, ACAT1, LDLR, and SCARB1 improved discrimination.
Conclusions: SQLE performs well as a single biomarker of prostate cancer lethality after primary therapy, in contrast to other markers of intratumoral cholesterol regulation. Improvements in prognostication are minimal when SQLE is added to a model that contains a centrally re-reviewed Gleason grade. Most importantly, SQLE may be an actionable, predictive biomarker of benefit from statin therapy, which addresses the cholesterol synthesis pathway regulated by SQLE.
Citation Format: Konrad H. Stopsack, Travis A. Gerke, Lorelei A. Mucci, Jennifer R. Rider. Prostate cancer prognostication based on an actionable metabolic pathway. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr PR09.
Abstract A04: Structural and functional caracterization of BARD1/CDK13 interaction
Authors: Fernandes Vanessa C. , Nepomuceno Thales C. , Carvalho Renato S. , Suarez-Kurtz Guilherme , Monteiro Alvaro N. , Carvalho Marcelo A. 
Published: May 2019

Abstract
DNA damage response (DDR) is crucial for cell survivor through genomic integrity maintenance. Dysfunctions in proteins implicated in DDR prompt cell to diseases, such as cancer. BRCA1 is a central protein involved in DDR and, once damaged, plays a pivotal role in cancer development. BRCA1 structure comprises two major domains, a RING finger domain and two tandem BRCT domains (tBRCT). This structure is shared by BRCA1 major interaction partner: BARD1. The tBRCT domain is commonly found in DDR-associated proteins. To study interactions in DDR, our group charted the tBRCT interactome for 7 different proteins, using three different strategies: tandem affinity purification followed by mass spectrometry (TAP-MS), yeast two hybrid (Y2H) screening, and literature curation. CDK13 was identified as a putative BARD1 tBRCT interactor by both TAP-MS and Y2H strategies. CDK13 is described as involved in several processes, such as chromatin remodeling, transcription regulation, and splicing coordination; however, its biological role remains unclear. To confirm BARD1/CDK13 interaction, whole cell extracts obtained from MCF-7 cells were used in coimmunoprecipitation assays using anti-CDK13 and anti-BARD1. Constructs encoding the HA-tagged regions 1-706aa (N-terminal), 706-982aa (kinase domain), and 1006-1452aa (C-terminal) of CDK13 were ectopically coexpressed with Flag-tagged full-length BARD1 or GFP-tagged BARD1 tBRCT in HEK293Tcells; whole cellular extracts were used in coimmunoprecipitation assays. BARD1 and CDK13 interaction was confirmed both in ectopic and constitutive expression approaches. CDK13 silencing was performed using lentiviral constructs encoding five different short hairpin RNAs (shRNA); MCF-7 cells were transduced and submitted to puromycin selection; extracts were used to evaluate CDK13 silencing by immunoblotting. Our data suggest that BARD1 tBRCT and the CDK13 N-terminal region, as well as the kinase domain, are critical for the formation of BARD1/CDK13 complex. MCF-7 cells lacking CDK13 expression will be used to investigate the kinase role during DDR.
Citation Format: Vanessa C. Fernandes, Thales C. Nepomuceno, Renato S. Carvalho, Guilherme Suarez-Kurtz, Alvaro N. Monteiro, Marcelo A. Carvalho. Structural and functional caracterization of BARD1/CDK13 interaction [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A04.
Abstract A06: MicroRNA-195 acts as a tumor suppressor miRNA in human melanoma cells by targeting Prohibitin 1
Authors: Cirilo Priscila D. R. , Côrrea Bruna R. S. , Qiao Mei , Andrade Luciana N. S. , Chammas Roger , Penalva Luiz O. F. 
Published: May 2019

Abstract
Melanoma is the most lethal type of skin cancer. Since chemo-resistance is a significant barrier, identification of regulators affecting chemo-sensitivity is necessary in order to create new forms of intervention. Here, we investigate the role of miR-195, its impact on Prohibitin 1 (PHB1) expression, and on chemo-sensitivity in melanoma cells. TCGA-RNAseq data obtained from 341 melanoma patient samples as well as a panel of melanoma lines were used in an expression correlation analysis between PHB1 and predicted miRNAs. miR-195 impact on PHB1 mRNA and protein levels and relevance of this regulation were investigated in UACC-62 and SK-MEL-5 melanoma lines by qRT-PCR and Western blot, luciferase reporter, and rescue experiments. Cell proliferation, hypodiploid, and caspase 3/7 assays were performed to investigate the potential action of miR-195 as chemo-sensitizer in melanoma cells treated with cisplatin and temozolomide. Analysis of the TCGA-RNAseq revealed a significant negative correlation (Pearson) between miR-195 and PHB1 expression. Moreover, qRT-PCR data showed that miR-195 is downregulated while PHB1 is upregulated in a collection of melanoma lines. We demonstrated that miR-195 regulates PHB1 directly by qRT-PCR and Western blot in melanoma cells and luciferase assays. To establish PHB1 as a relevant target of miR-195, we conducted rescue experiments in which we showed that PHB1 transgenic expression could antagonize the suppressive effect of miR-195 on the proliferation of melanoma cells. Finally, transfection experiments combined with drug treatments performed in the UACC-62 and SK-MEL-5 melanoma cells corroborated miR-195 as a tumor suppressor and potential chemo-sensitivity agent.
Citation Format: Priscila D. R. Cirilo, Bruna R. S. Côrrea, Mei Qiao, Luciana N. S. Andrade, Roger Chammas, Luiz O. F. Penalva. MicroRNA-195 acts as a tumor suppressor miRNA in human melanoma cells by targeting Prohibitin 1 [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A06.