tbuckley/cabot-search huggingface dataset:
Abstract 5131: Breast cancer with insertion or deletion exhibits the immunogenic phenotype
Authors: Peng Yuan, Xue Wang, Yuzi Zhang, Jing Zhao, Shangli Cai, Yongmei Yin
Journal: Cancer Research (2019)

Abstract Background: Although immunotherapy has been proven to be effective in a wide range of malignant tumors, breast cancer remains to be one of poorly immunogenic tumors and only a small subset of patients with breast cancer achieved benefits from immunotherapy. Therefore, identification of better predictive biomarkers to guide patient selection is highly desirable. It has been reported that insertion or deletion (indels) could create a novel open reading frame and generate more neoantigen which may mediate response to immunotherpay. However, the pattern of indels mutations in breast cancer is still unclear. Methods: Whole-exome sequencing data, RNA-Seq data and clinical data of 1096 breast tumors from The Cancer Genome Altas (TCGA) database were used to analyze the pattern of indels in breast cancer. Next generation sequencing (NGS) data of 81 breast tumors from clinical dataset were also used to validate the indels mutation pattern in different molecular subtype. Results: 81.7% (895/1096) of breast tumors in TCGA dataset harbored at least one indels mutation. Hormonal receptor (HR) negative tumors were associated with higher burden of indels mutations than HR positive tumors in both TCGA dataset (P = 0.05) and NGS-clinical dataset (P = 0.003). Indels were significantly correlated with higher TMB and neoantigen level in TCGA cohort (P &amp;lt; 0.0001). In addition, tumors with at least eight indels mutations (cut off as 80% percentile) exhibited even higher TMB (P &amp;lt; 0.0001) and neoantigen (P &amp;lt; 0.0001) level. Among 45 immune related genes, the mRNA expression of 22 genes were significantly higher in tumors with indels mutations, such as LAG3, IL18, IL6, CTLA4 and PDCD1. Indels group also showed a high levels of genome instability in terms of HRD-LOH (P = 0.004), NtAI (P = 0.000), wGII (P = 0.001) and LST (P =0.014). Conclusions: Breast tumors with indels mutations exhibited the immunogenic phenotype. Further studies are warranted to investigate the potential value of indels as a predictive biomarker for immunotherapy in breast cancer. Note: This abstract was not presented at the meeting. Citation Format: Peng Yuan, Xue Wang, Yuzi Zhang, Jing Zhao, Shangli Cai, Yongmei Yin. Breast cancer with insertion or deletion exhibits the immunogenic phenotype [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 5131.
Abstract 2533: The genomic and transcriptomic landscape of left versus right sided breast cancer in 410 cases
Authors: Yulia Newton, Christopher Szeto, Charles Vaske, Leia Reddy, Sandeep Reddy
Journal: Cancer Research (2019)

Abstract Background: Studies have shown that unilateral breast cancer is more common on the left (L) than right (R) and that the L breast is often larger than the R. No clear explanation for this finding has been described in the literature. Hypotheses range from complex genomic effects to environmental, hormonal, and anatomical causes. Methods: We performed a retrospective analysis of data from the NantHealth database of 410 commercial cases where WGS (35x germline, 75x somatic) or WES (∼150x). Primary and metastatic breast tumors were included in the analysis. Of these 410 cases, 39.3% were R, 38.5% were L, and 22% were unspecified. Bases adjacent to variant sites were used to determine genomic context (i.e. mutation signatures) as previously reported. Additionally, paired deep whole transcriptomic sequencing (RNA-Seq; ∼200x106 reads per tumor) was performed on 376 of the 410 cases. Nant Breast Cancer Intrinsic Subtypes sorting based on RNAseq assay classified breast tumors into 4 subtypes (LumA/B, Basal-like, and HER2-enriched). Results: Luminal A subtype was significantly overrepresented in R v L (OR=0.53, p=0.015). Similarly, R-side cases were significantly enriched for estrogen response gene expression by GSEA. However, only slight differential expression of ESR1 and MKI67 was observed specifically in individuals between 40 and 50 years old. Germline variants in the following genes were associated with sidedness: MEN1, KIT, JAK2, TET2, EP300, MET, FLCN, and KMT2D, and somatic variants within the following genes were associated with sidedness: CACNA1E, AGRN, RIMS2, TTYH3, KRTAP10-6, and DDX60L. However, significance of the variant frequency differences was lost after multiple-hypothesis correction. No significant differences between L and R were noted in tumor stage, HER2, ER, PR, somatic CNV, and mutation signatures, including signature 3 (BRCAness). Conclusions: Despite performing WGS/WES a paucity of differentially mutated genes were seen between left and right sided breast tumors. RNAseq analysis reveals that right sided breast cancers may be more likely to involve ESR1-signaling and be Luminal A subtype. Right-sided ESR1-signaling may be especially relevant in perimenopausal cases, however the current cohort is underpowered to achieve significance in this analysis. Citation Format: Yulia Newton, Christopher Szeto, Charles Vaske, Leia Reddy, Sandeep Reddy. The genomic and transcriptomic landscape of left versus right sided breast cancer in 410 cases [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 2533.
Abstract 13491: Relative Associations of Exercise Capacity With Ankle-Brachial Index vs Left Ventricular Function in Patients at Risk of Heart Failure: Preliminary Findings From the NIL-CHF Study
Authors: Julian W Sacre, Bronwyn A Kingwell, Chiew Wong, Yih K Chan, Simon Stewart, Melinda J Carrington
Journal: Circulation (2013)

Background: The ankle-brachial index (ABI) is associated with exercise capacity in pts with and without peripheral artery disease (PAD) but its significance relative to left ventricular (LV) functi...
Abstract 1069: New panel of patient derived lymphoma xenografts (PDX) for preclinical research and immune oncology
Authors: Bernadette Brzezicha, Michael Becker, Maria Stecklum, Teresia Conrad, Martin Janz, Aitomi Bittner, Clemens Schmitt, Ulrich Keilholz, Jens Hoffmann
Journal: Cancer Research (2019)

Abstract Lymphomas represent a very heterogeneous group of hematologic malignancies and pose an important challenge in the clinical routine. They frequently develop resistance to the treatment with standard-of-care (SoC) drugs and have a high incidence of disease recurrence. Recent progress in molecular high throughput profiling has helped to identify genetic drivers and genetic subtypes of diffuse large B-cell lymphomas (DLBCL). Further target validation and drug development projects are highly dependent on corresponding preclinical models representing the different clinical subtypes. Therefore, we started to establish and characterize new patient derived xenografts (PDX) of non-Hodgkin (NHL) and Hodgkin lymphomas (HL) for drug development, translational and immune oncology research. All lymphoma PDX were derived from peripheral blood, lymph node extirpations or core needle biopsies, and were usually transplanted subcutaneously into immunodeficient mice. For further characterization, established lymphoma PDX models were treated with SoC and investigational drugs. In addition, the growth of lymphoma PDX on humanized mice was evaluated to establish new models for the evaluation of novel immune therapy approaches. To gain a deeper insight in the molecular biology of the lymphoma models, RNA sequencing of all was performed. More than 20 new PDX models from NHL (including 8 DLBCL) and HL have been successfully established and characterized. Heterogeneous individual responses to the treatments were observed. Explorative analysis of RNA sequencing data confirmed the representation of the clinical lymphoma subgroups in our panel of models. Likewise, genetic subtypes of DLBCL COO classes could be confirmed by PCA and hierarchical clustering methods. Patterns of genetic driver mutations as revealed by recently published large genomic studies were identified. Our newly and extensively characterized lymphoma PDX model panel allows the evaluation on novel targeted and immune therapies in preclinical phase II trial settings. They provide an exceptional platform for the identification and validation of new targets and allow the preclinical screening of new combinations in translational research projects. Citation Format: Bernadette Brzezicha, Michael Becker, Maria Stecklum, Teresia Conrad, Martin Janz, Aitomi Bittner, Clemens Schmitt, Ulrich Keilholz, Jens Hoffmann. New panel of patient derived lymphoma xenografts (PDX) for preclinical research and immune oncology [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 1069.
Brentuximab vedotin with chemotherapy for stage III/IV classical Hodgkin lymphoma: 3-year update of the ECHELON-1 study
Authors: David J. Straus, Monika Długosz-Danecka, Sergey Alekseev, Árpád Illés, Marco Picardi, Ewa Lech-Maranda, Tatyana Feldman, Piotr Smolewski, Kerry J. Savage, Nancy L. Bartlett, Jan Walewski, Radhakrishnan Ramchandren, Pier Luigi Zinzani, Martin Hutchings, Joseph M. Connors, John Radford, Javier Munoz, Won Seog Kim, Ranjana Advani, Stephen M. Ansell, Anas Younes, Harry Miao, Rachael Liu, Keenan Fenton, Andres Forero-Torres, Andrea Gallamini
Journal: Blood (2020)
Quality of Life During Palliative Systemic Therapy for Esophagogastric Cancer: Systematic Review and Meta-Analysis
Authors: Jessy Joy van Kleef, Emil ter Veer, Héctor G van den Boorn, Sandor Schokker, Lok Lam Ngai, Mariska J Prins, Nadia Haj Mohammad, Lonneke V van de Poll-Franse, Aeilko H Zwinderman, Martijn G H van Oijen, Mirjam A G Sprangers, Hanneke W M van Laarhoven
Journal: JNCI Journal of the National Cancer Institute (2019)

Palliative systemic therapy can prolong life and reduce tumor-related symptoms for patients with advanced esophagogastric cancer. However, side effects of treatment could negatively affect health-related quality of life (HRQoL). Our aim was to review the literature and conduct a meta-analysis to examine the effect of palliative systemic therapy on HRQoL.EMBASE, Medline, and Central were searched for phase II/III randomized controlled trials until April 2018 investigating palliative systemic therapy and HRQoL. Meta-analysis was performed on baseline and follow-up summary values of global health status (GHS) and other European Organisation for Research and Treatment of Cancer scales. A clinically relevant change and difference of 10 points (scale 0-100) was set to assess the course of HRQoL over time within treatment arms as well as between arms.We included 43 randomized controlled trials (N = 13 727 patients). In the first-line and beyond first-line treatment setting, pooled baseline GHS mean estimates were 54.6 (95% confidence interval = 51.9 to 57.3) and 57.9 (95% confidence interval = 55.7 to 60.1), respectively. Thirty-nine (81.3%) treatment arms showed a stable GHS over the course of time. Anthracycline-based triplets, fluoropyrimidine-based doublets without cisplatin, and the addition of trastuzumab to chemotherapy were found to have favorable HRQoL outcomes. HRQoL benefit was observed for taxane monotherapy and several targeted agents over best supportive care beyond first line.Patients reported impaired GHS at baseline and generally remained stable over time. Anthracycline-based triplets and fluoropyrimidine-based doublets without cisplatin may be preferable first-line treatment options regarding HRQoL for HER2-negative disease. Taxanes and targeted agents could provide HRQoL benefit beyond first line compared with best supportive care.
Abstract 4921: TGF-beta signaling proteins and CYP24A1 may serve as surrogate markers for progesterone calcitriol treatment in ovarian and endometrial cancers of different histological types
Authors: Ana Paucarmayta, Hannah Taitz, Yovanni Casablanca, Gustavo C. Rodriguez, G L. Maxwell, Kathleen M. Darcy, Viqar Syed
Journal: Cancer Research (2019)

Abstract Strategies are needed to coordinately block drivers and induce suppressors of cancer to reduce incidence and improve outcomes for individuals with inherited or acquired risk. We previously reported the chemopreventive and therapeutic efficacy of the combination of progestin and calcitriol in transformed and malignant endometrioid endometrial cancer and in ovarian cancer models involving attenuated expression of TGF-β signaling proteins and progestin-mediated inhibition of calcitriol-induced CYP24A1 expression. This study aims to expand the applications for this combination to other subtypes of endometrial and ovarian cancers including those with mutations in ARID1A or PIK3CA, DNA mismatch repair deficiency or BRCA1-null status. The end points for this in vitro investigation included assessments of cell growth and the expression of TGF-β ligands, receptors, SMAD proteins and CYP24A1. Treatment of ovarian clear cell carcinoma, endometrioid carcinoma, papillary serous adenocarcinoma, BRCA1 null, and DNA mismatch repair deficient endometrial cancer cell lines with progesterone alone or in combination with calcitriol inhibited cell growth and expression of TGF-β1, TGF-β2, TGF-Rβ1, TGF-βR2, pSMAD2/3 and CYP24A1. Expression of TGF-βR3, SMAD-4, PR and VDR was not altered in any cell line tested except, ES-2, where VDR expression was upregulated in response to treatment. These results suggest that progesterone alone and progesterone-calcitriol combination have broad application in both chemopreventive and therapeutic settings that merit further development in a wide variety of ovarian and endometrial cancers, including those derived from germline or somatic mechanisms. Moreover, our data suggest that TGF-β signaling proteins and CYP24A1 may be effective surrogate markers indicative of treatment response. Citation Format: Ana Paucarmayta, Hannah Taitz, Yovanni Casablanca, Gustavo C. Rodriguez, G L. Maxwell, Kathleen M. Darcy, Viqar Syed. TGF-beta signaling proteins and CYP24A1 may serve as surrogate markers for progesterone calcitriol treatment in ovarian and endometrial cancers of different histological types [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 4921.
Abstract LB-012: US cancer centers of excellence coordination of operational strategies contribute to enhanced accrual of racial and ethnic minorities in clinical trials
Authors: Jeanne M. Regnante, Nicole A. Richie, Lola Fashoyin-Aje, Laura Lee Hall, Quita Highsmith, J'Aimee A. Louis, Kenneth Turner, Spencer C. Hoover, Simon Craddock Lee, Erin L. Williams, Homer Adams, Coleman Obasaju, Ify Sargeant, Madeline Geday, Marianne Gandee, Rayneisha Watson, Moon S. Chen
Journal: Cancer Research (2019)

Abstract Background: Racial and ethnic minority groups (REMGs) have low rates of inclusion in cancer trials. With the rise of precision medicine, it is critical that study populations in clinical research reflect the changing US demographics. Methods: Criteria were developed to identify cancer centers able to accrue a higher than average proportion of REMGs into clinical trials. Comprehensive interviews were conducted with leaders of identified cancer centers to ascertain operational strategies contributing to enhanced accrual of REMGs. Results: Eight representative centers reported a REMG accrual rate range in cancer research between 10-50% in a 12-month reporting period and met other criteria for inclusion, and 14 leaders participated in this assessment. Key findings were that centers: had a metric collection and reporting approach; routinely captured race and ethnicity data within databases accessible to research staff; had operational standards to support access and inclusion; developed practices to facilitate sustained patient participation during clinical trials; had strategies to decrease recruitment time and optimize clinical study design; and identified low-resource strategies for improving accrual. There was also a commitment to establish processes that support the patient’s provider as the key influencer of patient recruitment into clinical trials. Conclusion: Conduct of cancer research requires coordination of an operational framework governed by metrics in order to achieve high accrual of diverse populations in clinical trials. Leading US cancer centers have established key Operational Excellence practices and other notable practices which are critical for optimizing sustained inclusion of diverse populations in cancer clinical research. Citation Format: Jeanne M. Regnante, Nicole A. Richie, Lola Fashoyin-Aje, Laura Lee Hall, Quita Highsmith, J'Aimee A. Louis, Kenneth Turner, Spencer C. Hoover, Simon Craddock Lee, Erin L. Williams, Homer Adams, Coleman Obasaju, Ify Sargeant, Madeline Geday, Marianne Gandee, Rayneisha Watson, Moon S. Chen. US cancer centers of excellence coordination of operational strategies contribute to enhanced accrual of racial and ethnic minorities in clinical trials [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 LB-012.
Use of Guideline-Recommended Risk Reduction Strategies Among Patients With Diabetes and Atherosclerotic Cardiovascular Disease
Authors: Suzanne V. Arnold, James A. de Lemos, Robert S. Rosenson, Christie M. Ballantyne, Yuyin Liu, Katherine E. Mues, Shushama Alam, Mary Elliott-Davey, Deepak L. Bhatt, Christopher P. Cannon, Mikhail Kosiborod
Journal: Circulation (2019)
Abstract 16021: Chronic C-Type Natriuretic Peptide Causes Regression in Rat Model of Progressive Heart Failure: Insights into the Underlying Cellular Mechanism
Authors: Zhi Zhang, Heng-Jie Cheng, Zhe Chen, Peng Zhou, Tiankai Li, Nobuyuki Ohte, Satoshi Masutani, Che Ping Cheng
Journal: Circulation (2017)

Background: In addition to its well-known vasodilating and natriuretic actions, C-type natriuretic peptide (CNP), has been viewed as an endogenous inhibitor of the renin-angiotensin system. Emergin...
Constitutional SAMD9L Mutations Cause Familial Myelodisplastic Syndrome with Monosomy 7 and Stable Revertant Mosaicism
Authors: Victor Pastor Loyola, Sushree Sangita Sahoo, Jessica Boklan, Georg Schwabe, Brigitte Strahm, Dirk Lebrecht, Matthias Voss, Yenan T Bryceson, Miriam Erlacher, Gerhard Ehninger, Marena Niewisch, Brigitte Schlegelberger, Irith Baumann, John Achermann, Akiko Shimamura, Jochen Hochrein, Ulf Tedgaard, Lars Nilsson, Henrik Hasle, Melanie Börries, Hauke Busch, Charlotte M. Niemeyer, Marcin W. Wlodarski
Journal: Blood (2017)
Abstract 4224: SGLT2 is a diagnostic target for early stage lung adenocarcinoma
Authors: Brendon Villegas, Eva Koziolek, Jie Liu, W. Dean Wallace, David Elashoff, Denise R. Aberle, David B. Shackelford, Jorge R. Barrio, Jane Yanagawa, Steven M. Dubinett, Claudio Scafoglio
Journal: Cancer Research (2019)

Abstract Lung cancer is the leading cause of cancer-related death, and lung adenocarcinoma (LUAD) is the most frequent histology. Early diagnosis and treatment are essential; however, there are no targeted diagnostic and therapeutic approaches for early LUAD. An important hallmark of cancer is the increased glucose uptake via GLUT transporters. GLUT activity is imaged in cancer by positron emission tomography (PET) with 2-[18F] fluorodeoxyglucose (FDG). FDG PET is a standard tool for staging advanced lung cancer, but has low sensitivity for early-stage LUAD. This is considered a consequence of slow growth and low requirement of glucose. However, we discovered a novel system of metabolic supply not detected by FDG PET: the sodium glucose transporter 2 (SGLT2)1. SGLT2 activity can be measured in vivo with the PET tracer methyl-4-[18F] fluorodeoxyglucose (Me4FDG). We identified high expression of SGLT2 in human lung premalignancy and early-stage LUAD. Me4FDG detects early-stage, FDG-negative LUAD in mouse models. Targeting SGLT2 with FDA-approved inhibitors significantly reduces tumor growth and prolongs survival in genetic and patient-derived murine models, confirming an important role of SGLT2 in early-stage LUAD2. The reliance of early stage LUAD on SGLT2 opens exciting diagnostic and therapeutic opportunities. The National Lung Screening Trial showed a 20% reduction in lung cancer mortality in high risk individuals using low-dose helical computed tomography (CT). CT is highly sensitive for detecting lung nodules, but is limited by low specificity, especially for LUAD. On CT, LUAD may appear as solid or subsolid nodules. Most subsolid nodules are not cancer, and many will remain stable or resolve; however, subsolid lesions can represent premalignant lesions or adenocarcinoma in situ. These lesions in the early spectrum of LUAD may persist for months to years before transforming into invasive disease. As a result, current standard of care is to follow these patients with CT imaging to monitor these indeterminate lesions for radiologic signs of malignant progression. The identification of novel biomarkers to predict the malignant potential of these nodules at their initial identification is of paramount importance. 1Scafoglio et al. Proc Natl Acad Sci U S A 2015;112(30):E4111-4119 2Scafoglio et al. Sci. Transl. Med. 10, eaat5933 (2018) Citation Format: Brendon Villegas, Eva Koziolek, Jie Liu, W. Dean Wallace, David Elashoff, Denise R. Aberle, David B. Shackelford, Jorge R. Barrio, Jane Yanagawa, Steven M. Dubinett, Claudio Scafoglio. SGLT2 is a diagnostic target for early stage lung adenocarcinoma [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 4224.
Abstract 2493: The Treatment Paradox in Patients with Acute ST Elevation Myocardial Infarction: Decreasing Rate of Reperfusion Therapy with Increasing Clinical Risk
Authors: Uwe Zeymer, Anselm Gitt, Claus Jünger, Tobias Heer, Harm Wienbergen, Jochen Senges
Journal: Circulation (2006)

Background: Guideline recommended therapies have been shown to improve mortality in patients with STEMI. However, in clinical practice high risk patients often are not treated with reperfusion ther...