tbuckley/cabot-search huggingface dataset:
Abstract 2234: Monitoring of genetic change in circulating tumor DNA isolated from Her2 positive advanced gastric cancer patients
Authors: Woo Sun Kwon, Seung-Hyun Jung, Yeun-Jun Chung, Joong Bae Ahn, Hyun Cheol Chung, Sun Young Rha
Journal: Cancer Research (2019)

Abstract Gastric cancer is the common solid cancer and a leading cause for cancer related mortality worldwide. Despite developments and improvement in diagnosis, surgical technique, chemotherapy and radiotherapy, median survival time of advanced/metastatic gastric cancer (AGC) patients who received systemic chemotherapy is between 15-18 months. Tumor heterogeneity is associated with heterogeneous genetic profiling, which lowers diagnostic precision and consequently becomes an obstacle to determining the appropriate therapeutic strategies for individual cancer patients. Therefore, predictive biomarkers for determining potential treatment strategy are needed to improve the prognosis of patients. Personalized medicine has emerged as the future of cancer care to ensure that patients receive individualized treatment specific to their needs. In order to provide such care, molecular techniques that enable oncologists to diagnose, treat, and monitor tumors are necessary. Liquid biopsy by genotyping circulating tumor DNA (ctDNA) has provided a non-invasive and real-time liquid biopsy approach in assessing tumor genomic alterations in clinical oncology. This ctDNA have been associated with poor prognosis and clinical outcome in various cancer including lung, breast and colorectal. In this study, we evaluated utility and genetic profiling of ctDNAs in AGC. Under IRB approval, blood samples were collected in Cell-Free DNA BCT® streck tubes from 14 Her2-positive. Depending on the treatment schedule, blood can be collected 2 to 5 times per patient sequentially. The isolated ctDNAs were analyzed to genetic profiling by OncoChase (95 genes) based on AmpliSeq. And tumor tissue genotyping by CANCER MASTER and compared different sample preparation conditions. Validation of blood-based tumor genomic profiling in additional multicenter outcome studies is necessary; however, ctDNA monitoring can provide clinically important actionable information for precision oncology approaches. Citation Format: Woo Sun Kwon, Seung-Hyun Jung, Yeun-Jun Chung, Joong Bae Ahn, Hyun Cheol Chung, Sun Young Rha. Monitoring of genetic change in circulating tumor DNA isolated from Her2 positive advanced gastric cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2234.
Abstract 20793: Atrial Fibrillation Ablation Guided by Contact Force Measurement vs Standard Techniques: An Updated Systematic Review and Metaanalysis of Fifteen Studies
Authors: Omar Kreidieh, Jesus Pino, Bahij Kreidieh, Jaehyoung Choi, Justin Valente, Robert Fishel, Robert Chait
Journal: Circulation (2016)

Introduction: Contact force (CF) below 10g during afib ablation is associated with non-transmural lesions, but extremely high CF increases risk of perforation and other complications. Hypothesis: W...
Risankizumab compared with adalimumab in patients with moderate-to-severe plaque psoriasis (IMMvent): a randomised, double-blind, active-comparator-controlled phase 3 trial
Authors: Kristian Reich, Melinda Gooderham, Diamant Thaçi, Jeffrey J Crowley, Caitriona Ryan, James G Krueger, Tsen-Fang Tsai, Mary Flack, Yihua Gu, David A Williams, Elizabeth H Z Thompson, Carle Paul
Journal: The Lancet (2019)
Abstract 3387: Comprehensive detection and analysis of mutant-<i>SF3B1</i> splice pattern
Authors: Samar Alsafadi, Dorine Bellanger, Michele Cornella, Erik Lehnert, Sergio Roman-Roman, Marc-Henri Stern, Tatiana Popova
Journal: Cancer Research (2019)

Abstract Aberrant alternative splicing is emerging as a frequent and important process in cancer. Splice aberrations are mainly associated with missense mutations within genes encoding splice factors involved in 3′-splice site recognition. SF3B1, U2AF1, SRSF2 and ZRSR2 are the most frequently mutated genes encoding splicing factors in tumors. Interestingly, these mutations are mutually exclusive and each leads to a distinct aberrant splice pattern. Based on RNA-seq analyses of 74 primary tumors of uveal melanoma, we previously defined the aberrant splice pattern of SF3B1 hotspot mutations. In order to further characterize the catalogue of pathogenic mutations in SF3B1 that induce the aberrant splice pattern, we used a Sequence Bloom Tree (SBT) constructed from RNA-seq data for a total of 11,350 different tumors from the TCGA (Collaborative project with Seven Bridges Cancer Genome Cloud) to rapidly screen for samples consistent with the aberrant splice pattern. Based on this analysis, 75 tumors from different tissues of origin presented with the mutant-SF3B1 pattern, including 70 tumors harboring SF3B1 mutations: 48 cases of the hotspot mutations (21 tumors with SF3B1R625, 6 with SF3B1K666 and 21 with SF3B1K700) and 22 cases harbored non-hotspot SF3B1 mutations. No mutation or deletion in SF3B1 was detected in 5 tumors. Taking into account that the threshold of scores defining the significant presence of the aberrant splice pattern varies between tumor types, we proceeded to an in cellulo validation of a set of newly described mutations of SF3B1 and confirmed the induction of the aberrant splice pattern. Overall, our study highlights the potential of splice patterns as a biomarker in absence of detectable splice related mutations and sheds light on an efficient, large-scale computational approach to screen clinical cases for splice patterns. Citation Format: Samar Alsafadi, Dorine Bellanger, Michele Cornella, Erik Lehnert, Sergio Roman-Roman, Marc-Henri Stern, Tatiana Popova. Comprehensive detection and analysis of mutant-SF3B1 splice pattern [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3387.
Abstract 18996: Swirls and Twirls: Flow Patterns in the Reconstructed Aorta in Single Ventricles - A Cardiac Magnetic Resonance Four-Dimensional Flow Study
Authors: Mark A Fogel, Christine Li, Marc Keller, Kevin Whitehead, Matthew Harris
Journal: Circulation (2013)

Background: Flow patterns in the aorta are the result of the interplay of ventricular function and aortic geometry and have been implicated in the development of atherosclerotic disease, aortic dilation and aneurysm formation. It may also lend a clue to inefficient power output of the heart. Previous work from our laboratory has demonstrated decreased power output in pts with single right ventricles (SRV) as compared with single left ventricle pts; this may be partially due to the necessity of aortic reconstruction (recon) in SRV pts. The purpose of this study is to determine the flow patterns in recon. Methods: A retrospective review of all SRV pts who underwent cardiac magnetic resonance 4-dimensional phase contrast flow imaging from January 2012 to the present. The phase contrast slab was obtained in the candycane view of the aorta. Post processing was performed using GT Flow. Results: A total of 11 SRV pts who underwent recon were found, ages 5.1± 1.8 yrs with cardiac index of 4.8± 1.8 liters/minute/meter 2 ; 5 with Fontan and 6 with bidirectional Glenn/HemiFontan. A right handed helix (clockwise when viewed in the direction of flow) was visualized in all pts in the ascending aorta (AAo); in one who had a markedly dilated transverse arch, a secondary helical pattern was created in that region. In pts with a narrowed isthmus (46± 4.3% of AAo diameter), helical flow changed to a left handed helix in the descending aorta (DAo); in those without narrowing (65± 11% of AAo diameter), little helical flow was noted in the DAo (P=0.05). Conclusion: SRV undergoing recon demonstrated a right handed helix in the AAo; those with a narrowed isthmus demonstrated a reversal of the helix to a left handed pattern in the DAo while those without narrowing showed little secondary flow. Significant isthmus narrowing alters secondary flow patterns in the DAo. These observations may yield a clue to decreased SRV power output.
Abstract 54: Characterization of patient-derived organoids cultured on a gas-rich, liquid-liquid interface
Authors: James T. Shoemaker, Katherine R. Richardson, Jamie Arnst, Adam Marcus, Jelena Vukasinovic
Journal: Cancer Research (2019)

Abstract Modeling tissues in vitro has long consisted of two-dimensional (2D) monolayer cultures grown in a dish, flask, or multi-well plate. While these methods remain adequate for some applications, the advent of personalized cancer therapies has necessitated the development of more complex models that more accurately represent the in vivo environment. Attempting to characterize tumor cell biology and response to candidate pharmaceuticals in 2D cultures has led to results that fail to translate to clinical therapies. A key source of this failure is the loss of cell diversity due to selective pressure resulting in cell populations that favor adhering to a rigid substrate. Three-dimensional (3D) cell culture methods have produced models that capture many of the dynamics of the in vivo tissue environment. Patient-derived organoids (PDOs) are quickly becoming the most attractive solution for creating predictive, patient-specific tumor models in vitro. Typically grown as spheroids, these models still present limitations in terms of cell survival and recapitulation of tumor development. Lena Biosciences has previously developed complex, vascularized tissue models using patented 3D scaffolds and a perfusion system. Hepatocytes grown in this system demonstrated increased cell viability and recovery of cytochrome P450 enzyme activity compared to 2D controls. Integral to the perfusion system is a pure, synthetic liquid that is twice as dense as and immiscible with cell culture medium and reagents. It is permissive to atmospheric gases, providing a gas-rich, liquid-liquid interface below 3D cultures maintained in the system. We hypothesized that PDOs could be cultured without a 3D scaffold, directly at the interface between the cell culture medium and this synthetic liquid. A specific preparation of this interface resulted in lung-derived PDOs that spontaneously formed dense, 3D, tissue-like structures that showed increased viability (as measured by a 50% reduction in LDH release) and cellular respiration (three-fold increase as measured by an alamarBlue assay). Ongoing studies are focused on characterizing PDOs from other patients and other tissues as they develop in long-term in vitro studies. Should this PDO model prove to be a faithful representation of in vivo tumor development, this system would be ideal for applications such as testing drug efficacy and studying mechanisms of tumor metastasis. Citation Format: James T. Shoemaker, Katherine R. Richardson, Jamie Arnst, Adam Marcus, Jelena Vukasinovic. Characterization of patient-derived organoids cultured on a gas-rich, liquid-liquid interface [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 54.
A core laboratory approach to large-scale radiomics and machine-learning prediction of DLBCL outcomes after first-line treatment using results from the phase III GOYA study.
Authors: Stephane Chauvie, Federico Dalmasso, Larry Pierce, Tina Nielsen, Deniz Sahin, Calvin Lee, Federico Mattiello, Lale Kostakoglu, Paul Kinahan
Journal: Journal of Clinical Oncology (2019)

e19042 Background: We are using the phase 3 GOYA study to retrospectively investigate using quantitative image texture features (i.e. radiomics, evaluating tumor heterogeneity) to improve the prognostic value of baseline FDG-PET. We report on the considerations for analysis, which is ongoing, and solutions to methodological challenges. Methods: GOYA, an open-label, randomized, phase 3 study, enrolled 1418 patients from 207 centers; 1334 had a baseline FDG-PET scan with detectable lesions. Image data with annotated regions of interest (ROIs) defined by qualified physicians were transferred to the Cuneo imaging core laboratory. Images were interpolated to a common 4x4x4 mm voxel size and ROI masks using 4 different definition methodologies were used to define image sub-volumes that contained the lesions. Large ROIs in normal liver were also defined. The 42 Haralick radiomic image texture features were computed using the PET oncology radiomics test suite. Results: A total of 9286 lesions were analyzed. Interpolation of images to a fixed size is challenging in this cohort due the large number of features to be computed (~1.5M). As a test, the lesions were differentiated from liver ROIs using 5 classifiers (e.g. support vector machine, random forest, etc) with an accuracy of 0.995–0.999. The mean (±SD) of the metabolically active tumor volume was 21.2±22.2 mL (range 0.2–146 mL) with a preponderance of smaller lesions as shown by the median of 15.0 mL. The skewed distribution had downstream effects on many of the quantitative (e.g. total lesion glycolysis) and radiomic image texture features. The majority of texture features were computable; 5 (Coarseness, Contrast, Busyness, Complexity, Texture Strength) required interpolation to a 2x2x2 mm voxel size, requiring extended computation time. FDG-PET images came from a variety of PET/CT scanners; thus, a unified image reconstruction protocol was not possible. Conclusions: Radiomics analysis of large phase 3 imaging trials is feasible. However, careful attention should be paid to the entire processing chain, including tests for non-computable features values due to highly skewed distributions and lesion size. Clinical trial information: NCT01287741.
Abstract 4171: Identification of individuals with colonic polyposis in a highly inbred region
Authors: Tirzah Braz Petta Lajus, Ana Rafaela Timoteo
Journal: Cancer Research (2019)

Abstract Familial adenomatous polyposis (FAP), also known as colonic polyposis, is a hereditary autosomal dominant disease, responsible for only 1% of colorectal cancer (CRC) in the population. FAP patients with a germline mutation in the APC gene have a 100% risk of developing CRC. MAP (Mutyh associated polyposis) is the polyposis associated with biallelic mutations in the MUTYH gene, and carriers are at risk of developing CRC. Few studies propose heterozygous Mutyh mutation is associated with high risk for breast cancer, but the results are conflicting. In the city Caicó, Brazil, we identified 8 non-related breast cancer patients with the same mutation c.536A&amp;gt;G, p.Tyr179Cys. In this region we find high frequencies of consanguineous marriages, which varied from about 9% to 32%, suggesting a direct association to genetic diseases. We hypothesize the founding mutation MUTYH_c.536A&amp;gt;G was established during Dutch colonization in Brazil between 1620 and 1650. For this, we are developing a population-based, case-control study of all newly diagnosed breast cancer in this city. In our group we have one oncologist, one psychologist and one geneticist. We recruited the patients (index-cases) from the archives in the Laboratory of Pathology at the Hospital Liga contra o Cancer and we invited the individuals to participate in the research. Citation Format: Tirzah Braz Petta Lajus, Ana Rafaela Timoteo. Identification of individuals with colonic polyposis in a highly inbred region [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4171.
Abstract 17129: Low Density Lipoprotein Cholesterol Response After Statin Initiation Among HIV-positive Persons With High Risk for Cardiovascular Disease Events
Authors: Greer Burkholder, Paul Muntner, Hong Zhao, Michael Mugavero, E T Overton, Meredith Kilgore, Dan Drozd, Heidi Crane, Richard Moore, Chris Mathews, Elvin Geng, Steve Boswell, Michelle Floris-Moore, Ben Taylor, Keri Monda, Robert S Rosenson
Journal: Circulation (2016)

Introduction: The 2013 ACC/AHA cholesterol guideline recommends use of moderate- or high-intensity statins to reduce LDL-C and the risk of CVD events in high-risk groups. Meta-analyses of general p...
Abstract 2030: Inhibiting the GAS6/AXL axis suppresses tumor progression by blocking the interaction between cancer-associated fibroblasts and cancer cells in gastric carcinoma
Authors: Dagyoeng Lee, Jongsu Woo, Cheong A Bae, In-Hye Ham, Hye Jung Oh, Sang-Yong Son, Sang-Uk Han, Tae-Min Kim, Jung Hwan Yoon, Won Sang Park, Hoon Hur
Journal: Cancer Research (2019)

Abstract Cancer-associated fibroblasts (CAF) are a major component of tumor stroma and their effect on the progression of gastric carcinoma (GC) has recently been demonstrated. However, agents targeting the interaction between CAF and GC cells have not been applied in a clinical setting. The aim of this study was to investigate the effect of an AXL inhibitor on CAF-induced GC progression. We examined growth arrest specific factor 6 (GAS6) expression and phosphorylation of AXL in various cell lines, including GC cells and non-cancerous cells, by qPCR, western blot, and immunocytochemistry. We investigated the role of CAF-derived GAS6 on the migration and proliferation of GC cells using migration and cell survival assays. The effect of the AXL inhibitor, Bemcentinib, on the CAF-induced aggressive phenotype of GC cells was also investigated. Finally, we performed immunohistochemistry to measure the phosphorylation of AXL in a tissue microarray composed of 175 GC tissues, and evaluated its correlation with the prognosis of GC patients. qPCR and western blot analysis showed that GAS6 expression was higher in CAF relative to other cells. We found that CAF increased the phosphorylation of AXL (P-AXL), differentiation into a mesenchymal-like phenotype, and cell survival in GC cell lines. When the expression of AXL was inhibited in GC cells, the effect of CAF was reduced. In addition, Bemcentinib, a small molecule inhibitor of AXL, suppressed the effects of CAF on GC cell lines. In GC tissues, P-AXL positively correlated with the expression of vimentin (P &amp;lt; 0.001) and high levels of P-AXL were significantly associated with poor overall survival (P = 0.022).These findings suggest that CAF is a major source of GAS6 in the GC microenvironment and actively promotes an aggressive phenotype in GC cells through AXL activation. We conclude that an AXL inhibitor may be a novel agent for GC treatment. Citation Format: Dagyoeng Lee, Jongsu Woo, Cheong A Bae, In-Hye Ham, Hye Jung Oh, Sang-Yong Son, Sang-Uk Han, Tae-Min Kim, Jung Hwan Yoon, Won Sang Park, Hoon Hur. Inhibiting the GAS6/AXL axis suppresses tumor progression by blocking the interaction between cancer-associated fibroblasts and cancer cells in gastric carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2030.
Correction: The effect of a programme to improve men's sedentary time and physical activity: The European Fans in Training (EuroFIT) randomised controlled trial
Authors: Sally Wyke, Christopher Bunn, Eivind Andersen, Marlene N. Silva, Femke van Nassau, Paula McSkimming, Spyros Kolovos, Jason M. R. Gill, Cindy M. Gray, Kate Hunt, Annie S. Anderson, Judith Bosmans, Judith G. M. Jelsma, Sharon Kean, Nicolas Lemyre, David W. Loudon, Lisa Macaulay, Douglas J. Maxwell, Alex McConnachie, Nanette Mutrie, Maria Nijhuis-van der Sanden, Hugo V. Pereira, Matthew Philpott, Glyn C. Roberts, John Rooksby, Øystein B. Røynesdal, Naveed Sattar, Marit Sørensen, Pedro J. Teixeira, Shaun Treweek, Theo van Achterberg, Irene van de Glind, Willem van Mechelen, Hidde P. van der Ploeg
Journal: PLoS Medicine (2019)

[This corrects the article DOI: 10.1371/journal.pmed.1002736.].
Abstract 1721: FOXO1, a downstream substrate of AKT, function as tumor suppressor in HCC carcinogenesis
Authors: Shu Zhang, Xin Chen
Journal: Cancer Research (2019)

Abstract Hepatocellular carcinoma (HCC) represents the fifth most common tumor types in the world and the third leading cause of cancer-related death. However, the signaling pathways underlying hepatic pathogenesis are still poorly understood, hence lacking of effective targeted therapy. Activation of PI3K/AKT signaling cascade has been implicated in HCC development. It has been well-established that the mammalian target of rapamycin complex 1 (mTORC1), is a major downstream effector of AKT. The reason why mTORC1 can be consistently activated is partly due to inactive mutations of a negative element regulating mTORC1, tuberous sclerosis 2 (TSC2), found in 10% human HCCs. Beyond TSC2, forkhead Box O transcription factor 1 (FOXO1), is another AKT substrate. It has been proved that FOXO1 plays a crucial role in the insulin signal pathway and liver regeneration relying on AKT isoforms. However, the role of FOXO1 in HCC development has not been well established. Here we report, by using TCGA database the mRNA level of FOXO1 significantly decreases among the FOXO family, comparing tumor tissue to the surrounding tissue. The overall survival rate favors patients with high FOXO1 expression level. The inhibition efficacies of a pan-AKT inhibitor, in both TSC2 wide type cells and TSC2-null ones, indicating TSC2 is not the only target downstream of AKT. Protein analysis shows the activity of mTORC1 can still be inhibited as well as the phosphorylation of FOXO1 in TSC2-null cells. Therefore, we hypothesize that in the presence of TSC2, AKTi can suppress the activation of mTORC1 directly through TSC2. Otherwise, in the absence of TSC2, AKTi can still inhibit mTORC1 via activation of FOXO1. Furthermore, we overexpress the activated FOXO1 (FOXO1 AAA) in TSC2-null HCC cell lines. Cell growth are significantly prohibited, implicating FOXO1 is a tumor suppressor in HCC cells. Over expression of activated FOXO1 can also delay mTORC1 activation based HCC in AKT/Ras FVB mice model.Lesions consist mainly of clear-cell hepatocytes, owing to an increase in glycogen and fat storage. Proliferation is nearly the same within the neoplastic nodules. Activated AKT occurs both in the cytoplasm and on the membrane. Interestingly, FOXO1AAA escapes into the cytoplasm instead of remaining in the nuclei where it should stay. In a conclusion, AKT/mTORC1 can be a classic molecular pathway for HCC pathogenesis. Nevertheless, the parallel substrate of AKT, FOXO1, may also be an important factor in a TSC2 independent way. Citation Format: Shu Zhang, Xin Chen. FOXO1, a downstream substrate of AKT, function as tumor suppressor in HCC carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1721.
Abstract 11063: Impaired Cerebral Autoregulation in Preoperative Newborn Infants with Congenital Heart Disease
Authors: Jodie K Votava-Smith, Michael D Taylor, Erik C Michelfelder, Jesse M Pratt, David P Nelson, Charles S Kleinman
Journal: Circulation (2012)

Objectives: Our goal was to characterize cerebral autoregulation (CA) in preoperative newborn infants with congenital heart disease (CHD). Methods: This is a prospective pilot study of full-term ne...
Gevokizumab, an interleukin-1β (IL-1β) monoclonal antibody (mAb), in metastatic colorectal cancer (mCRC), metastatic gastroesophageal cancer (mGEC) and metastatic renal cell carcinoma (mRCC): “first-in-cancer” phase Ib study
Authors: E. Van Cutsem, K. Shitara, W. Deng, A. Vaury, L. Tseng, X. Wang, J. Millholland, M. Shilkrut, B. Mookerjee, E. Jonasch
Journal: Annals of Oncology (2019)