tbuckley/cabot-search huggingface dataset:
Abstract 605: Association of blood lipid profile and lung cancer risk: Results from the Southern Community Cohort Study
Authors: Yan Sun, Jie Wu, Hyung-Suk Yoon, Wei Zheng, William J. Blot, Qiuyin Cai
Journal: Cancer Research (2019)

Abstract Lung cancer is the second most common cancer and the leading cause of cancer death in the U.S. African Americans (AAs) have a higher incidence rate than any other racial group. Lipid metabolism and homeostasis play important roles in the growth of cancer cells and the regulation of membrane proteins. Some previous epidemiological studies have evaluated the association between blood lipid levels and lung cancer risk; however, the results were inconsistent, and few explored patterns among AAs. To investigate the association of blood lipid levels and lung cancer risk, particularly in a low socioeconomic population and AAs, we conducted a nested case-control study using resources from the Southern Community Cohort Study, a well-characterized prospective cohort study of approximately 86,000 adult men and women, two-thirds of whom are AAs. Blood lipid profiles, including total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TRIG), and lipoprotein-a (Lp-a), were measured in 372 lung cancer cases and 721 matched controls. AAs had lower median levels of TRIG, and higher levels of HDL and Lp-a than European Americans (EAs). Conditional logistic regression analysis revealed an inverse association between TC and lung cancer risk, with an adjusted OR for the highest vs. lowest tertiles of 0.67 (95% CI: 0.45-0.99). This association was observed in both AAs and EAs, but was only statistically significant in EAs. Further stratified analysis found that this association was only significant in cases that were diagnosed within 2 years of blood collection. No significant associations of other lipid markers with lung cancer risk were observed. The findings from our study suggest that the inverse associations between TC and lung cancer risk more likely resulted from cancerous occurrence and progression and associated lifestyle changes rather than being indicative of causal markers. Citation Format: Yan Sun, Jie Wu, Hyung-Suk Yoon, Wei Zheng, William J. Blot, Qiuyin Cai. Association of blood lipid profile and lung cancer risk: Results from the Southern Community Cohort Study [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 605.
Enhanced Potency of GalNAc-Conjugated Antisense Oligonucleotides in Hepatocellular Cancer Models
Authors: Youngsoo Kim, Minji Jo, Joanna Schmidt, Xiaolin Luo, Thazha P. Prakash, Tianyuan Zhou, Stephanie Klein, Xiaokun Xiao, Noah Post, Zhengfeng Yin, A. Robert MacLeod
Journal: Molecular Therapy (2019)

Antisense oligonucleotides (ASOs) are a novel therapeutic approach to target difficult-to-drug protein classes by targeting their corresponding mRNAs. Significantly enhanced ASO activity has been achieved by the targeted delivery of ASOs to selected tissues. One example is the targeted delivery of ASOs to hepatocytes, achieved with N-acetylgalactosamine (GalNAc) conjugation to ASO, which results in selective uptake by asialoglycoprotein receptor (ASGR). Here we have evaluated the potential of GalNAc-conjugated ASOs as a therapeutic approach to targeting difficult-to-drug pathways in hepatocellular carcinoma (HCC). The activity of GalNAc-conjugated ASOs was superior to that of the unconjugated parental ASO in ASGR (+) human HCC cells in vitro, but not in ASGR (-) cells. Both human- and mouse-derived HCC displayed reduced levels of ASGR, however, despite this, GalNAc-conjugated ASOs showed a 5- to 10-fold increase in potency in tumors. Systemically administered GalNAc-conjugated ASOs demonstrated both enhanced antisense activity and antitumor activity in the diethylnitrosamine-induced HCC tumor model. Finally, GalNAc conjugation enhanced ASO activity in human circulating tumor cells from HCC patients, demonstrating the potential of this approach in primary human HCC tumor cells. Taken together, these results provide a strong rationale for a potential therapeutic use of GalNAc-conjugated ASOs for the treatment of HCC.
Abstract 4152: Irreversible electroporation induces immunogenic cell death and mediates durable response in orthotopic PDAC model in combination with anti-PD-1
Authors: Jun Zhao, Xiaofei Wen, Tingting Li, Marites Melancon, Sanjay Gupta, Weiyi Peng, Chun Li
Journal: Cancer Research (2019)

Abstract Immunotherapy has only limited efficacy against pancreatic ductal adenocarcinoma (PDAC) because of the presence of an immunosuppressive tumor-associated stroma. Here, we showed that combined IRE and anti-PD-1 immune checkpoint blockade significantly suppressed tumor growth and prolonged the lives of immunocompetent mice bearing well-established orthotopic PDAC. Remarkably, more than 35% of mice had a durable response, and were found to be free of residual tumor upon necropsy. All mice that survived for 60 days after IRE and anti-PD1 treatments rejected tumor cell re-challenge. Analyses of splenocytes confirmed that these long-term survivors developed an anti-tumor memory T cell response. Further mechanistic studies unveiled that the efficacy of IRE + anti-PD-1 could be attributed to multiple factors, including rapid release of danger associated molecular patterns, activation of DCs, and alleviation of immunosuppressive tumor microenvironment. Neutralization of CD8+ T cells by anti-CD8 antibody nullified the antitumor effect of combined IRE and anti-PD-1, suggesting that tumor-infiltrating CD8+ T cells played a key role in mediating the anti-tumor efficacy of IRE + anti-PD-1.Given that both IRE and anti-PD-1 antibodies are already used in the clinic, our results support the translation of this combination as a promising approach for treating patients with PDAC. Citation Format: Jun Zhao, Xiaofei Wen, Tingting Li, Marites Melancon, Sanjay Gupta, Weiyi Peng, Chun Li. Irreversible electroporation induces immunogenic cell death and mediates durable response in orthotopic PDAC model in combination with anti-PD-1 [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 4152.
Abstract 5090: Epitope mapping of mouse TERT for vaccine development
Authors: Yurong Song, Jason Marshall, Travis Kerr, Ligia Pinto, Shizuko Sei, Robert Shoemaker
Journal: Cancer Research (2019)

Abstract Telomerase reverse transcriptase (TERT) is one of two essential components of telomerase, an enzyme complex that generates and maintains telomeres. Telomerase is expressed mainly in embryonic and adult stem cells. Telomere biology has recently been implicated in the pathogenesis of a variety of diseases, and mutations in telomerase components result in a predisposition to solid malignancies. More recent findings show that TERT is not only expressed in late stage primary tumor cells and metastatic cells, but also expressed in incipient cancer stem cells and/or tumor-initiating cells, indicating that TERT has essential roles at every stage of tumorigenesis. However, the clinical benefit of a TERT (hTERT)-targeting vaccine, given as a single agent or in combination with chemotherapeutic agents, has been limited in patients with advanced cancer, possibly due to insufficient epitope coverage as well as tumor-induced immune suppression. Thus, targeting TERT in tumor-initiating cells in early stage lesions may be more effective in preventing cancer development and progression. To develop cancer preventive TERT vaccines, novel immunogenic epitopes must be first identified and evaluated in a relevant preclinical model of tumorigenesis. The goal of this project is to identify the epitopes of mouse TERT with high immunogenicity using MHC I-peptide binding assay by flow cytometry analysis. The in vitro peptide-induced MHC Class I stabilization assay was carried out using RMA/S cell line, which was derived from a Rauscher leukemia virus-induced C57BL/6 T cell lymphoma and is deficient in transporter associated with antigen processing (TAP). Results of screening the overlapping peptide library will be presented. Funded by NCI Contract No. HHSN261200800001E Citation Format: Yurong Song, Jason Marshall, Travis Kerr, Ligia Pinto, Shizuko Sei, Robert Shoemaker. Epitope mapping of mouse TERT for vaccine development [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 5090.
Outcomes of stem cell transplant in patients with Richter transformation.
Authors: Yucai Wang, Marcella Tschautscher, Kari G. Rabe, Sameer Ashok Parikh, Timothy Call, Eli Muchtar, Neil E. Kay, Jose Francisco Leis, Amber Koehler, Patrick B. Johnston, David James Inwards, Luis F. Porrata, William J. Hogan, Saad Kenderian, Wei Ding
Journal: Journal of Clinical Oncology (2019)

7526 Background: Stem cell transplant (SCT) was considered to be beneficial in CLL patients with Richter transformation (RT). We report a single center experience of SCT for RT. Methods: CLL patients with biopsy-confirmed RT to DLBCL who underwent SCT were identified from Mayo Clinic CLL database, and clinical information was abstracted by chart review. Survival analysis was done with the Kaplan-Meier method. Results: Twenty-four of 204 RT patients underwent SCT, 20 autologous and 4 allogeneic. The median lines of prior CLL therapy was 1 (range 0-4). Only 4 patients were exposed to ibrutinib prior to RT. The median age at RT diagnosis was 62 (range 41-73). Five of 17 (29%) patients had bulky disease (≥ 5 cm), 12 of 20 (60%) had elevated LDH, and 6 of 15 (40%) had TP53 disruption (del(17p) or TP53 mutation). The median lines of RT therapy prior to SCT was 2 (range 1-4); treatments included R-CHOP-like alone (n = 7), platinum-based alone (n = 1), both R-CHOP-like and platinum-based (n = 11), novel agents (n = 2), and high dose MTX-based (n = 3). Response prior to SCT was CR in 12 (50%) and PR in 12 (50%) patients. The median time from RT diagnosis to SCT was 6.8 months (range 3.3-42.3). After a median follow-up of 52.7 months after SCT, there were 10 RT relapses, 4 CLL progression, and 11 deaths (7 RT, 1 CLL and 3 unrelated). The median progression-free survival (PFS) was 28.5 months (95% CI 8.3-NA; 1-year PFS 61.8%, 2-year PFS 50.5%). The median post-SCT survival was 56.3 months (95% CI 30.6-76.6; 2-year survival 82.0%, 4-year survival 65.6%). Elevated LDH was associated with worse PFS (median 8.9 months vs NA, P= 0.014) and a trend of worse post-SCT survival (53.7 vs 67.4 months, P= 0.153). Other factors including age, prior CLL treatment (untreated vs treated), bulky disease, response prior to SCT, and TP53 disruption were not associated with PFS or post-SCT survival. Among the 4 allogeneic SCT patients, 1 had RT relapse 10.5 months after SCT and was treated with venetoclax, ibrutinib and obinutuzumab and remained alive at last follow-up (12.9 months after SCT). All 3 other patients remained in remission and alive at last follow up (15.6, 16.1 and 108.5 months after SCT, respectively). Conclusions: SCT may benefit select RT patients. The role of SCT in the novel agent era needs further study.
Accelerated Allograft Vasculopathy With Rituximab After Cardiac Transplantation
Authors: Randall C. Starling, Brian Armstrong, Nancy D. Bridges, Howard Eisen, Michael M. Givertz, Abdallah G. Kfoury, Jon Kobashigawa, David Ikle, Yvonne Morrison, Sean Pinney, Josef Stehlik, Sudipta Tripathi, Mohamed H. Sayegh, Anil Chandraker, Barbara Gus, Karen Keslar, Bill Magyar, John Petrich, Randall C. Starling, W. H. Wilson Tang, Kimberly Brooks, Michael Givertz, Charles Kelly, Katie Klein, Kerry Crisalli, Sandra DeBronkart, Joren Madsen, Marc Semigran, John Vetrano, Teresa DeMarco, Scott Fields, Carol Maguire, Robert Gordon, Allen Anderson, Jane Regalado, Anna Warzecha, Lee Goldberg, Caroline Olt, Kenneth Rockwell, Ashley Harris, Maryl Johnson, Susan Johnston, Chris Roginski, Rashid Ahmed, Ivy Cohen, Denise Peace, Sean Pinney, Tina Yao, Gloria Araujo, Arvind Bhimaraj, Eunice Karanga, Varsha Patel, Julie Chait, Mario Deng, Gregg Fonarow, Christina Shin, Charles Gibbs, Judson Hunt, Melissa Johnson, Tina Worley, Jeff Gibbs, John Kirk, Winter Redd, Josef Stehlik, Julia Bryan, Anna French, A.G. Kfoury, Kristin Konery, Erika Feller, Myounghee Lee, Richard Pierson, Cindi Young, Theodora Hollifield, Kimberley Porter, Mariann Schulz, Adrian VanBakel, Kiran Khush, Helen Luikart, Son Nguyen, Michael Pham, David DeNofrio, Ryan O’Kelly, Lucilla Garcia, Jon Kobashigawa, Sean Sana, Brandy Starks, Maria Thottam, Annie Yi, Barry Cabuay, Rachel Olson, Larry Tucker, Laura Uppgaard, Howard Eisen, Denise Lai, Colleen Poisker, Klaudija Dragicevic, Harrison Kelner, Darlette Luke, Jennifer Nelson, Ganesh Raveendran, Nick Kleissas, Srinivas Murali, Kenneth Rayl, Sarah Sherry, Michele Cosgrove
Journal: Journal of the American College of Cardiology (2019)
Abstract 2983: LpMab-23: an anti-podoplanin cancer-specific antibody for a prognostic marker of oral cancer
Authors: Takashi Miwa, Shinji Yamada, Mika K. Kaneko, Yoshikazu Furusawa, Masato Fukui, Yukinari Kato
Journal: Cancer Research (2019)

Abstract Background Podoplanin (PDPN) is a specific ligand of C-type lectin-like recepotor-2 (CLEC-2), and is involved in cancer metastasis. The physiological PDPN function has been discussed in many normal tissues, including lymphatic endothelial cells, pulmonary type I alveolar cells, and renal podocytes. Herein, we aimed to produce cancer-specific anti-PDPN monoclonal antibodies (mAbs). Furthermore, we investigated whether the reactivity of cancer-specific anti-PDPN mAbs might be a prognostic marker of oral cancer. Materials and methods We immunized mice with LN229/PDPN cells, and screened mAbs, which react with PDPN-expressing cancer cell lines, such as glioblastoma cell lines and lung squamous cell carcinoma cell lines and do not react with PDPN-expressing normal cells, including primary lymphatic endothelial cells and renal epithelial cell lines in flow cytometry. Furthermore, we investigated the reactivity of anti-PDPN mAbs by immunohistochemistry against oral cancers. Anti-tumor activities by mouse-human chimeric LpMab-23 (chLpMab-23) were examined using mouse xenograft models of oral cancer cells. Finally, we analyzed the association between the reactivity of anti-PDPN mAbs and clinical/pathological features of oral cancers. Results We established LpMab-23, a cancer-specific anti-PDPN mAb. LpMab-23 reacted with PDPN-expressing cancer cell lines in flow cytometry. In contrast, LpMab-23 recognized PDPN-expressing normal cells very weakly. LpMab-23 reacted only with PDPN-expressing cancer cells, not with lymphatic endothelial cells in oral cancer tissues by immunohistochemistry. The epitope mapping of anti-PDPN mAbs revealed that LpMab-23 recognized a cancer-specific glycopeptide including Thr55/Ser56. chLpMab-23 revealed high ADCC and anti-tumor activities against oral cancers. The Kaplan-Meier curves of the five-year new metastasis-free survival rate (nMFS) were significantly lower in LpMab-23-positive patients than in the patients with LpMab-23-negative ones. Conclusions A cancer-specific anti-PDPN mAb (LpMab-23) and its mouse-human chimeric mAb (chLpMab-23) were successfully established. LpMab-23 is advantageous in anti-tumor activities. LpMab-23-positive cases could be a useful predictor of poor prognosis for oral cancer. Citation Format: Takashi Miwa, Shinji Yamada, Mika K. Kaneko, Yoshikazu Furusawa, Masato Fukui, Yukinari Kato. LpMab-23: an anti-podoplanin cancer-specific antibody for a prognostic marker of oral cancer [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 2983.
Endoscopic submucosal dissection of giant colorectal lesion using the “multiple-clip-facilitated rubber-band method”
Authors: Guan Yi Liu, Long Rong, Yun Long Cai, Wei Dong Nian
Journal: Endoscopy (2019)

Colorectal endoscopic submucosal dissection (ESD) is considered to be one of the most challenging procedures. To perform colorectal ESD safely and efficiently, clear visualization of the submucosal layer is essential, especially for giant lesions. Various traction methods have been developed to improve the visibility of the submucosal layer [1] [2] [3]; however, few can offer continuous traction with changeable direction. Recently, we modified the rubber-band method and called the new traction method the "multiple-clip-facilitated rubber-band method" (MCRM).
Abstract 12479: CHA2DS2-VASc Clinical Predictors Are Associated With Stroke in Patients With Acute Coronary Syndrome Independently of Atrial Fibrillation: A Systematic Review and Meta-analysis on 690.000 Patients
Authors: Federico Guerra, Lorena Scappini, Gianluca C Campo, Rita Pavasini, Alessandro Capucci
Journal: Circulation (2015)

Introduction: Stroke is a rare but serious complication of acute coronary syndrome (ACS), its incidence depending on well defined risk factors. Hypothesis: To test whether clinical variables included in the CHA2DS2-VASc score keep their predictive value even in patients with recent ACS, regardless of atrial fibrillation (AF) presence. Methods: Meta-analysis was performed according to the PRISMA guidelines. MEDLINE and EMBASE were searched using the following query: (“stroke OR embolism”) AND “acute coronary syndrome” NOT “atrial fibrillation”. At the end of the selection process, 21 papers (10 randomized clinical trials and 11 observational studies) were entered into the meta-analysis. The following variables were taken into account: heart failure, hypertension, age, diabetes mellitus, previous stroke, gender and previous vascular disease. RRs was used as the main effect size. Because of the large heterogeneity in studies’ characteristics, a random-effects model was used and each variable was tested separately for randomized clinical trials and for observational studies before entering the pooled analysis. The interaction between clinical features and presence of atrial fibrillation was tested by performing a random effect meta-regression. Results: The whole cohort included 690.309 patients. Median follow-up was 9 months. Advanced age and previous stroke resulted as the most important risk factors for stroke (RR 5.89. 95% CI 4.92-6.86 for advanced age and RR 2.83. 95% CI 2.36-3.38 for previous stroke), in accordance with the two-point value that both of them have in the CHA2DS2-VASc score. All other factors were positively associated with stroke, albeit RRs were lower (heart failure RR 1.57 95% CI 1.32-1.86; hypertension RR 1.19; 95% CI 1.13-1.26; female gender RR 1.26, 95% CI 1.18-1.36; diabetes mellitus RR 1.35, 95% CI 1.25-1.46; vascular disease RR 1.35, 95% CI 1.11-1.63). Although AF confirmed its association with stroke (RR 2.13, 95% CI 1.82-2.49), its interaction on aforementioned variables was not significant. Conclusions: All risk factors included in the CHA2DS2-VASc score are associated with stroke in patients with ACS, making it an useful tool for risk stratification in patients with ACS, regardless of AF presence.
Abstract 16111: Modeling and Spatial Assessment of a Bystander Notification System for Out-of-hospital Cardiac Arrests in Pittsburgh, PA
Authors: Sanjana Srinivasan, David D Salcido
Journal: Circulation (2016)

Introduction: Rapid cardiopulmonary resuscitation (CPR) or defibrillation with an automated external defibrillator (AED) can increase rate of survival after an OHCA. Bystander notification systems ...
Abstract 1654: Detection of structural variations in a cancer reference sample with multiple NGS platforms
Authors: Yongmei Zhao, Wenming Xiao
Journal: Cancer Research (2019)

Abstract Structural Variations (SVs) are genetic variations or rearrangements in the structure of chromosome. SVs study plays an important role in cancer research as cancer genome is commonly altered with thousands of structural rearrangements such as insertions, deletions, translocation, inversions, duplications, copy number variations (CNVs). Next-generation sequencing (NGS) technology has provided a cost-effective approach for the comprehensive detection of SVs in human cancer cells. In this study, we systematically investigated the somatic structural variations in a pair of breast cancer cell lines with multiple NGS platforms including Illumina short-read, 10x genomics linked-read, PacBio long-read, and high-throughput chromosome conformation capture HiC. We systematically evaluated the factors that impact the SVs detection accuracy. We measured the reproductivity of somatic SV detections across platforms and benchmarked the different software tools’ performance. We performed SV integration from different platforms and established a high-confident SV call set for the reference samples. To independently evaluate the accuracy of our SV call set, we used orthogonal methods such as cytogenetic array as well as fusion gene detected from RNA-seq for cross validation. From this study, we identified the unique strengths of each NGS technologies and provide a practical guide to integrate multiple platform data to improve SV detection sensitivity and accuracy in cancer genome. Note: This abstract was not presented at the meeting. Citation Format: Yongmei Zhao, Wenming Xiao, on behalf of Somatic Mutation Working Group of theSEQC2 Consortium. Detection of structural variations in a cancer reference sample with multiple NGS platforms [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 1654.
EndoTAG-1 plus gemcitabine versus gemcitabine alone in patients with measurable locally advanced and/or metastatic adenocarcinoma of the pancreas failed on FOLFIRINOX treatment
Authors: M. Su, L. Chen, E. Hitre, W. Lee, L. Bai, Z. Papai, S. Kang, M. Dvorkin, M. Lee, E. Ludovic, H. Choi, S. Oh, G. Bodoky, P. Artru, J. Hwang, I. Bazin, F. Bosc, J. Bachet, Z. Horváth, C. Chang, J. Lin
Journal: Annals of Oncology (2019)