tbuckley/cabot-search huggingface dataset:
Abstract B38: Identification of stage-wise miRNAs signature as potential biomarker in head and neck squamous cell carcinoma
Authors: Sugandh Kumar, Anshuman Dixit
Journal: Clinical Cancer Research (2020)

Abstract The head and neck squamous cell carcinoma (HNSCC) is one of the predominant causes of cancer-related casualties globally. The high mortality rate of HNSCC is due to late diagnosis, and the overall survival rate is less than 50%. The early detection of a primary tumor and prevention of relapse are the major research challenges associated with various cancer including HNSCC. However, currently, not one molecular marker has been widely accepted for routine use in managing patients with HNSCC. Therefore, a study relating the association between clinical stages and different coding/noncoding expression profiles is very much required to identify the potential biomarker for early detection and therapeutics. In the current study, we have analyzed TCGA transcriptomics (i.e., miRNAs, mRNAs) profile to extract meaningful molecular signature in different TNM stages of HNSCC. Further, we used machine learning and other regression approaches to identify the signature miRNAs as a biomarker in various stages of cancer. The analysis revealed uncovered miRNAs with stage-dependent alterations in expression (has-miR-31, miR-143, miR-202, miR-135b, let-7, etc.) specifically expressed in early clinical stages whereas (miR-636, miR-1, miR-99a and miR-3934) specifically expressed in later stages. Kaplan-Meier survival analysis also revealed that some of the identified miRNA used as a potential prognostic biomarker. The top enriched regulatory genes involved in ECM degradation, Nicotine Degradation III, EMT, Integrin signaling and IL-10 in early stages were at later stage pathways, i.e., glucose metabolism. The combination of stage-specific miRNAs could be used for the target of oncogenesis and chemoresistance pathways. Initial stage biomarkers may prove to be essential tools in the timely diagnosis of the disease and improved overall survival outcome. We hope the current study for biomarker identification will open new opportunities for the development of effective diagnostic and therapeutic drug for HNSCC in the future. Citation Format: Sugandh Kumar, Anshuman Dixit. Identification of stage-wise miRNAs signature as potential biomarker in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B38.
Combination therapy with T cell engager and PD-L1 blockade enhances the antitumor potency of T cells as predicted by a QSP model
Authors: Huilin Ma, Hanwen Wang, Richard J Sové, Jun Wang, Craig Giragossian, Aleksander S Popel
Journal: Journal for ImmunoTherapy of Cancer (2020)

T cells have been recognized as core effectors for cancer immunotherapy. How to restore the anti-tumor ability of suppressed T cells or improve the lethality of cytotoxic T cells has become the main focus in immunotherapy. Bispecific antibodies, especially bispecific T cell engagers (TCEs), have shown their unique ability to enhance the patient's immune response to tumors by stimulating T cell activation and cytokine production in an MHC-independent manner. Antibodies targeting the checkpoint inhibitory molecules such as programmed cell death protein 1 (PD-1), PD-ligand 1 (PD-L1) and cytotoxic lymphocyte activated antigen 4 are able to restore the cytotoxic effect of immune suppressed T cells and have also shown durable responses in patients with malignancies. However, both types have their own limitations in treating certain cancers. Preclinical and clinical results have emphasized the potential of combining these two antibodies to improve tumor response and patients' survival. However, the selection and evaluation of combination partners clinically is a costly endeavor. In addition, despite advances made in immunotherapy, there are subsets of patients who are non-responders, and reliable biomarkers for different immunotherapies are urgently needed to improve the ability to prospectively predict patients' response and improve clinical study design. Therefore, mathematical and computational models are essential to optimize patient benefit, and guide combination approaches with lower cost and in a faster manner.In this study, we continued to extend the quantitative systems pharmacology (QSP) model we developed for a bispecific TCE to explore efficacy of combination therapy with an anti-PD-L1 monoclonal antibody in patients with colorectal cancer.Patient-specific response to TCE monotherapy, anti-PD-L1 monotherapy and the combination therapy were predicted using this model according to each patient's individual characteristics.Individual biomarkers for TCE monotherapy, anti-PD-L1 monotherapy and their combination have been determined based on the QSP model. Best treatment options for specific patients could be suggested based on their own characteristics to improve clinical trial efficiency. The model can be further used to assess plausible combination strategies for different TCEs and immune checkpoint inhibitors in different types of cancer.
Predicting Progression to Advanced Age-Related Macular Degeneration from Clinical, Genetic, and Lifestyle Factors Using Machine Learning
Authors: Soufiane Ajana, Audrey Cougnard-Grégoire, Johanna M. Colijn, Bénédicte M.J. Merle, Timo Verzijden, Paulus T.V.M. de Jong, Albert Hofman, Johannes R. Vingerling, Boris P. Hejblum, Jean-François Korobelnik, Magda A. Meester-Smoor, Marius Ueffing, Hélène Jacqmin-Gadda, Caroline C.W. Klaver, Cécile Delcourt, Erkin I. Acar, Blanca Arango-Gonzalez, Angela Armento, Franz Badura, Vaibhav Bhatia, Shomi S. Bhattacharya, Marc Biarnés, Anna Borrell, Sofia M. Calado, Sascha Dammeier, Anita de Breuk, Berta De la Cerda, Anneke I. den Hollander, Francisco J. Diaz-Corrales, Sigrid Diether, Eszter Emri, Tanja Endermann, Lucia L. Ferraro, Míriam Garcia, Thomas J. Heesterbeek, Sabina Honisch, Carel B. Hoyng, Ellen Kilger, Elod Kortvely, Claire Lastrucci, Hanno Langen, Imre Lengyel, Phil Luthert, Jordi Monés, Everson Nogoceke, Tunde Peto, Frances M. Pool, Eduardo Rodriguez-Bocanegra, Luis Serrano, Jose Sousa, Eric Thee, Marius Ueffing, Karl U. Ulrich Bartz-Schmidt, Markus Zumbansen
Journal: Ophthalmology (2020)
Abstract 6161: PARP inhibition enhances radiotherapy of SMAD4 deficient human head and neck squamous cell carcinomas in experimental models
Authors: Christian D. Young, Ariel L. Hernandez, Li Bian, Sana D. Karam, David Raben, Xiao-Jing Wang
Journal: Cancer Research (2020)

Abstract Purpose: SMAD4 loss causes genomic instability and the initiation/progression of head and neck squamous cell carcinoma (HNSCC). Here, we study if SMAD4 loss sensitizes HNSCCs to olaparib (PARP inhibitor) in combination with radiotherapy (RT). Experimental Design: We analyzed HNSCC TCGA data for SMAD4 expression in association with FANC/BRCA family gene expression. Human HNSCC cell lines were screened for sensitivity to olaparib. Isogenic HNSCC cell lines were generated to restore or reduce SMAD4 expression and treated with olaparib, radiation, or the combination. HNSCC pretreatment specimens from a Phase I trial investigating olaparib were analyzed. Results: SMAD4 levels correlated with levels of FANC/BRCA genes in HNSCC. HNSCC cell lines with SMAD4 homozygous deletion were sensitive to olaparib. In vivo, olaparib or RT monotherapy reduced tumor volumes in SMAD4 mutant but not SMAD4 positive tumors. Olaparib with RT dual therapy sustained tumor volume reduction in SMAD4 deficient (mutant or knockdown) xenografts, which exhibited increased DNA damage and cell death compared to vehicle treated tumors. In vitro, olaparib or in combination with radiation caused lower clonogenic survival, more DNA damage-associated cell death and less proliferation in SMAD4 deficient cells than in SMAD4-positive (endogenous SMAD4 or transduced SMAD4) cells. Applicable to clinic, 5 out of 6 SMAD4-negative HNSCCs and 4 out of 8 SMAD4-positive HNSCCs responded to a standard treatment plus olaparib in a Phase I clinical trial, and SMAD4 protein levels inversely correlated with DNA damage. Conclusion: SMAD4 levels are causal in determining sensitivity to PARP inhibition in combination with RT in HNSCCs. Citation Format: Christian D. Young, Ariel L. Hernandez, Li Bian, Sana D. Karam, David Raben, Xiao-Jing Wang. PARP inhibition enhances radiotherapy of SMAD4 deficient human head and neck squamous cell carcinomas in experimental models [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6161.
Abstract 11163: Lipid Monitoring and Treatment Intensification of Cholesterol Lowering Therapies - Insight From the Veterans Affairs Healthcare System
Authors: Xiaoming Jia, David J Ramsey, Mahmoud al Rifai, Sarah T Ahmed, Julia M Akeroyd, Dave L Dixon, Tyler J Gluckman, Vijay Nambi, Christie M Ballantine, Laura A Petersen, Neil J Stone, Salim S Virani
Journal: Circulation (2019)

Introduction: The 2013 and 2018 Blood Cholesterol guidelines recommend monitoring of lipids to assess efficacy and adherence to cholesterol lowering therapy. Lipid testing provides clinical data th...
Narrowing the Gap for Hematopoietic Cell Transplantation in the East-Mediterranean/African Region: Comparison with Global HSCT Indications and Trends. A Report on Behalf of the East Mediterranean (EMBMT), African Blood and Marrow Transplantation Group (AFBMT) and Worldwide Network for Blood and Marrow Transplantation (WBMT)
Authors: Dietger Niederwieser, Mahmoud Aljurf, Helen Baldomero, Syed Ziauddin A. Zaidi, Shahrukh K. Hashmi, Ardeshir Ghavamzadeh, Alaa M. Elhaddad, Rose-Marie Hamladji, Parvez Ahmed, Lamia Torjemane, Miguel R Abboud, Abdelghani Tbakhi, Maurtada Khamis Al-Khabori, Asma Quessar, Nosa Bazuaye, Mohamed Amine Bekadja, Salman Naseem Adil, Omar Fahmy, Mani Ramzi, Ahmad Ibrahim, Lahoucine Mahmal, Amr Nassar, Fazal Hussain, Hassan El Solh, Nour Ben Abdeljelil, Amir Ali Hamidieh, Amal Al-Seraihy, Mohamed Al Huneini, Yoshihisa Kodera, Hildegard T. Greinix, Mary M. Horowitz, Daniel J. Weisdorf, Alois Gratwohl, Jakob R. Passweg, Jeff Szer, Nicolas Novitzky
Journal: Blood (2017)
Abstract B17: Functional characterization of HPV-human fusion transcripts in oropharyngeal cancer
Authors: Lisa M. Pinatti, Heather M. Walline, Thomas E. Carey
Journal: Clinical Cancer Research (2020)

Abstract Human papillomavirus (HPV) genomic integration is frequently seen in oropharyngeal squamous cell carcinoma (OPSCC). Integration into cellular genes can cause the generation of HPV-host fusion transcripts, which have been associated with worse survival in OPSCC patients, but their functional consequences are unknown, as HPV alone is capable of transformation. The forced expression of fusion transcripts versus HPV transcripts in spontaneously immortalized human oral keratinocytes (NOKSI) could demonstrate their effects on cell behavior. Our research focuses on characterizing HPV integration sites and fusion transcripts in cell lines and tumors, followed by in vitro analysis of fusion transcript function. By Detection of Integrated Papillomavirus Sequences (DIPS-PCR) and RT-PCR, we have identified integration events and fusion transcripts in a subset of samples in both intergenic and genic regions of the genome. We began our analysis with two fusion transcripts, one reading from HPV16 E6*-E7-E1 into the tumor suppressor gene TP63 from UM-SCC-47 and the other reading from HPV16 E6*-E4 into the solute carrier gene SLC47A2 from UM-SCC-104. The full fusion transcripts and associated controls were cloned into lentiviral vectors, and stable keratinocyte populations expressing these transcripts were selected. These cultures were subjected to proliferation, migration, and invasion assays. Subsequent in-depth molecular characterization and in vivo studies will help clarify their effects on cancer formation and metastasis. These studies will advance our understanding of how fusion transcripts lead to worse patient survival and help develop new therapies for these patients. Citation Format: Lisa M. Pinatti, Heather M. Walline, Thomas E. Carey. Functional characterization of HPV-human fusion transcripts in oropharyngeal cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B17.
Digital advantage in the COVID-19 response: perspective from Canada’s largest integrated digitalized healthcare system
Authors: Daniel C. Baumgart
Journal: npj Digital Medicine (2020)

The SARS-CoV-2 pandemic has challenged healthcare systems worldwide. Uncertainty of transmission, limitations of physical healthcare system infrastructure and supplies as well as workforce shortages require dynamic adaption of resource deployment to manage rapidly evolving care demands, ideally based on real time data for the entire population. Moreover, shut down of traditional face-to-face care infrastructure requires rapid deployment of virtual health care options to avoid collapse of health organizations. The Alberta Electronic Health Record Information System is one of the largest population based comprehensive electronic medical record (EMR) installations. Alberta's long standing solid telehealth hardware-, training-, provider remuneration- and legislation infrastructure has enabled quick transition to virtual healthcare. Virtual health services including asynchronous secure clinical communications, real-time virtual care via messaging, telephony or video conferencing (telehealth) and ancillary functions like triage, scheduling, documentation and reporting, the previously established virtual hospital program with home monitoring, virtual health assessments, medication review, education and support for patients and families and coordination between family doctors, specialists and other health team members help to control viral transmission, protect healthcare personnel and save supplies. Moreover, rapid launch of online screening and triage tools to guide testing and isolation, online result sharing, infected patient and contact tracing including a smartphone exposure tracking application (ABTraceTogether), electronic best practice alerts and decision support tools, test and treatment order sets for standardized COVID-19 management, continuous access to population level real-time data to inform healthcare provider, public health and government decisions have become key factors in the management of a global crisis in Alberta.
Abstract 913: Defining melanoma patients unresponsive to single agent anti-PD-1 therapy but responsive to combination anti-PD-1 + anti-CTLA-4 therapy
Authors: Jarem J. Edwards, Inês Pires da Silva1, Angela Ferguson, Peter Johansson, Jordan Conway, Grace Attrill, Robyn P.M Saw, John F. Thompson, Alexander M. Menzies, Umaimainthan Palendira, Georgina V. Long, Richard A. Scolyer, James S. Wilmott
Journal: Cancer Research (2020)

Abstract Background: A proportion of patients that fail single agent anti-PD-1 therapy will subsequently receive and respond to combination anti-PD-1 and anti-CTLA-4 immunotherapy. The clinical and biological characteristics of these patients remain poorly defined and as such there are presently no reliable validated biomarkers to distinguish patients requiring the addition of anti-CTLA-4 in the context of anti-PD-1 therapy. Clinical cohort and methods: We performed RNA sequencing, immunofluorescence-IHC, and multiparameter image-mass cytometry (IMC) on formalin-fixed paraffin embedded (FFPE) tumors at baseline and post anti-PD-1 therapy from n=15 stage IV melanoma patients who failed anti-PD-1 therapy and went on to receive combination immunotherapy (7 non-responders; 8 responders). Results: Tumor pathological parameters including TIL and neutrophil densities, fibrosis, necrosis and mitotic rates identified were not different between responders and non-responders. While T-reg, cytotoxic CD8 and CD39+ resident CD8 T cells densities were not significantly different, the proportion of TCF7+ CD8 T cells was significantly higher at baseline (p=0.01) and in all tumor samples (p=0.007) in responders compared to non-responders. RNA differential gene expression analysis revealed higher expression of cancer testis antigens (CTAs) in responding patient tumors. Hierarchical clustering of differentially expressed genes separated responding patients from non-responding patients. Conclusions: The proportion of TCF7+ CD8 T cells and the presence of melanoma cancer testis antigens may be a predictive biomarker of response to combination immunotherapy in patients failing anti-PD-1 monotherapy but requires further validation. Citation Format: Jarem J. Edwards, Inês Pires da Silva1, Angela Ferguson, Peter Johansson, Jordan Conway, Grace Attrill, Robyn P.M Saw, John F. Thompson, Alexander M. Menzies, Umaimainthan Palendira, Georgina V. Long, Richard A. Scolyer, James S. Wilmott. Defining melanoma patients unresponsive to single agent anti-PD-1 therapy but responsive to combination anti-PD-1 + anti-CTLA-4 therapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 913.
Five-Year Analysis of Adjuvant Dabrafenib plus Trametinib in Stage III Melanoma
Authors: Reinhard Dummer, Axel Hauschild, Mario Santinami, Victoria Atkinson, Mario Mandalà, John M. Kirkwood, Vanna Chiarion Sileni, James Larkin, Marta Nyakas, Caroline Dutriaux, Andrew Haydon, Caroline Robert, Laurent Mortier, Jacob Schachter, Thierry Lesimple, Ruth Plummer, Kohinoor Dasgupta, Eduard Gasal, Monique Tan, Georgina V. Long, Dirk Schadendorf
Journal: New England Journal of Medicine (2020)

In the previously reported primary analysis of this phase 3 trial, 12 months of adjuvant dabrafenib plus trametinib resulted in significantly longer relapse-free survival than placebo in patients with resected stage III melanoma with BRAF V600E or V600K mutations. To confirm the stability of the relapse-free survival benefit, longer-term data were needed.
Abstract 5436: Purification and mRNA profiling of extracellular vesicles for early detection of hepatocellular carcinoma
Authors: Yi-Te Lee, Na Sun, Ryan Y. Zhang, Rueihung Kao, Pin-Jung Chen, Pai-Chi Teng, Jasmine J. Wang, Yingying Yang, Minhyung Kim, Edwin M. Posadas, Sungyong You, Ju Dong Yang, Vatche G. Agopian, Hsian-Rong Tseng, Yazhen Zhu
Journal: Cancer Research (2020)

Abstract Hepatocellular carcinoma (HCC) is the 4th most common cause of cancer-related deaths worldwide. The poor prognosis of HCC is due to the fact that diagnosis is often made at an advanced stage in disease development. It is crucial to develop a non-invasive liquid biopsy-based diagnostic solution for early detection of HCC. In this study, we developed a covalent chemistry-based nanostructured silicon substrate (“EV Click Chip”) for the isolation of HCC extracellular vesicles (EVs). The EV Click Chip leverages specific click chemistry reactions and sensitive multi-marker cocktail antibody identification of the HCC EVs. The EV Click Chip also allows for the subsequent release of the captured HCC EVs and is optimal for the downstream molecular analysis. A well-validated 10 liver-specific genes were quantified using reverse transcription droplet digital PCR (RT-ddPCR) in HCC EVs purified by the optimized EV Click Chips for the detection of HCC. Our EV Click Chip-based HCC-EV Assay is able to differentiate HCC from non-HCC controls (chronic liver diseases, healthy donors and other cancers) and outperformed clinical AFP test for distinguishing early-stage HCC from at-risk cirrhotic patients. Citation Format: Yi-Te Lee, Na Sun, Ryan Y. Zhang, Rueihung Kao, Pin-Jung Chen, Pai-Chi Teng, Jasmine J. Wang, Yingying Yang, Minhyung Kim, Edwin M. Posadas, Sungyong You, Ju Dong Yang, Vatche G. Agopian, Hsian-Rong Tseng, Yazhen Zhu. Purification and mRNA profiling of extracellular vesicles for early detection of hepatocellular carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5436.
OP0015 SEX-SPECIFIC U-SHAPED RELATIONSHIP BETWEEN SERUM URATE AND MORTALITY IN THE UNITED STATES GENERAL POPULATION
Authors: K. D’silva, C. Yokose, L. Lu, Y. Zhang, H. Choi
Journal: Annals of the Rheumatic Diseases (2020)

Background: A U-shaped relationship may exist between serum urate (SU) and cardiovascular events, although the relationship between SU and mortality is unclear. The most recent EULAR recommendations for gout advise against maintaining SU &lt;3 mg/dl for prolonged periods. Objectives: To examine the relationship between SU and all-cause and cause-specific mortality in large cohorts in the United States (US). Methods: We examined National Health and Nutrition Examination Survey (NHANES) data from 1988-1994 (NHANES III) and 1999-2007 including subjects aged ≥18 with an enrollment SU measurement. We used Cox proportional hazards regression models to estimate sex-specific mortality risk relative to a referent SU 5-6 mg/dL, adjusting for NHANES cycle, age, race, body mass index (BMI), education, alcohol use, smoking, hypertension, total cholesterol, estimated glomerular filtration rate (GFR), and competing risks, using age as a time scale for survival analysis. Results: Among 19,954 men and 21,853 women, there were 5,714 male deaths and 4,901 female deaths (median follow-up 14.2 ± 6.9 years). Among men, there was a 33% increased all-cause mortality risk at SU &lt;4 mg/dL (HR 1.33, 95% CI 1.17-1.51) and 52% increased all-cause mortality risk at SU &gt;8 mg/dL (HR 1.52, 95% CI 1.37-1.69) compared to subjects with SU 5-6 mg/dL, driven by cause-specific mortality from diabetes at low SU and chronic lower respiratory diseases and cardiovascular disease at high SU ( Table ). In women, there was no increased mortality risk at low SU and a 45% increased all-cause mortality risk at SU &gt;7 mg/dL (HR 1.45, CI 1.31-1.61) compared to subjects with SU 5-6 mg/dL, driven by cause-specific mortality from diabetes. Mortality from Alzheimer’s disease was lower at high SU among men (HR 0.23, 95% CI 0.05-0.99) and women (HR 0.54, 95% CI 0.25-1.15). Table. Multivariable hazard ratios for all-cause and cause-specific mortality in NHANES III and 1999-2007. Conclusion: In large cohorts representative of the US population, there was a U-shaped relationship between SU and all-cause mortality in men but not women. In men with low SU, mortality was driven primarily by diabetes, which may be explained by the uricosuric effect of uncontrolled hyperglycemia in diabetes patients. The lower mortality from Alzheimer’s disease at high SU agrees with previously shown inverse associations between gout and Alzheimer’s disease. Further studies are needed to determine the presence of causality underlying these associations. Disclosure of Interests: Kristin D’Silva: None declared, Chio Yokose: None declared, Leo Lu: None declared, Yuqing Zhang: None declared, Hyon Choi Grant/research support from: Ironwood, Horizon, Consultant of: Takeda, Selecta, Horizon, Kowa, Vaxart, Ironwood