tbuckley/cabot-search huggingface dataset:
Integrated Genomic Characterization of the Human Immunome in Cancer
Authors: Yongsheng Li, Brandon Burgman, Daniel J. McGrail, Ming Sun, Dan Qi, Sachet A. Shukla, Erxi Wu, Anna Capasso, Shiaw-Yih Lin, Catherine J. Wu, S. Gail Eckhardt, Gordon B. Mills, Bo Li, Nidhi Sahni, S. Stephen Yi
Journal: Cancer Research (2020)

Abstract Alterations in immune-related pathways are common hallmarks of cancer. A comprehensive understanding of how cancer mutations rewire immune signaling networks and functional output across cancer types is instrumental to realize the full potential of immunotherapy. Here, we systematically interrogated somatic mutations involved in immune signaling that alter immune responses in patients with cancer. To do so, we developed a Network-based Integrative model to Prioritize Potential immune respondER genes (NIPPER). Identified mutations were enriched in essential protein domains and genes identified by NIPPER were associated with responsiveness to multiple immunotherapy modalities. These genes were used to devise an interactome network propagation framework integrated with drug-associated gene signatures to identify potential immunomodulatory drug candidates. Together, our systems-level analysis results help interpret the heterogeneous immune responses among patients and serve as a resource for future functional studies and targeted therapeutics. Significance: This study demonstrates that integration of multi-omics data can help identify critical molecular determinants for effective targeted therapeutics.
Abstract 16488: Mild Valvular Lesions and Long-Term Cardiovascular Risk in the Community: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Kunihiro Matsushita, Jonathan Rubin, Lucia Kwak, Ajay Kirtane, Susheel Kodali, Elizabeth Selvin, Alvaro Alonso, Martin B Leon, Scott Solomon, Josef Coresh, Ervin Fox, Amil M Shah
Journal: Circulation (2018)

Background: Evidence linking valvular disease to prognosis is derived mainly from studies of patients requiring medical or surgical therapy. There is limited information on the long-term prognostic...
Abstract 1657: Paired agent fluorescence imaging of cancer in a living mouse using targeted molecular probes with emission wavelengths of 690 and 830 nm
Authors: Cynthia L. Spires (Schreiber), Canjia Zhai, Janel Dempsey, Hannah McGarraugh, Braden Matthews, Caroline Christmann, Bradley Smith
Journal: Cancer Research (2020)

Abstract Targeted fluorescent probes were used for cancer imaging and assessing tumor targeting performance in a living mouse model. Untargeted probes and targeted probes (appended with cRGDfK peptide units for integrin targeting on cancer cells) were fabricated with emission wavelengths of 690 and 830 nm. Selective targeting of cancer cells was proved by series of cell microscopy experiments followed by in vivo imaging of subcutaneous tumors in living mice. The mouse imaging studies included a mock surgery that completely removed a fluorescently labeled tumor. Enhanced tumor accumulation due to probe targeting was first evaluated by conducting Single Agent Imaging (SAI) experiments that compared tumor imaging performance of a targeted probe and untargeted probe in separate mouse cohorts. Although there was imaging evidence for enhanced tumor accumulation of the targeted probe, there was moderate scatter in the data due to tumor-to-tumor variability of the vasculature structure and interstitial pressure. A subsequent Paired Agent Imaging (PAI) study co-injected a binary mixture of targeted probe (with emission at 690 nm) and untargeted probe (with emission at 830 nm) into the same tumor-burdened animal. The conclusion of the PAI experiment also indicated enhanced tumor accumulation of the targeted probe but the statistical significance was much higher, even though the experiment required a much smaller cohort of mice. The imaging data from the PAI experiment was analyzed to determine the targeted probe's Binding Potential (BP) for available integrin receptors within the tumor tissue. In addition, pixelated maps of BP within each tumor indicated a heterogenous spatial distribution of BP values. The results of this study show that PAI is a promising new way to analyze tumor heterogeneity and its eventual use in clinical applications such as targeted therapy, image guided surgery, and personalized medicine. Citation Format: Cynthia L. Spires (Schreiber), Canjia Zhai, Janel Dempsey, Hannah McGarraugh, Braden Matthews, Caroline Christmann, Bradley Smith. Paired agent fluorescence imaging of cancer in a living mouse using targeted molecular probes with emission wavelengths of 690 and 830 nm [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 1657.
Abstract 3462: Gender differences in dietary behavior and urinary gallic acid concentrations in racial minorities in New York City
Authors: Cristina Zambrano, Wenyue Lu, Cicely Johnson, Maayan Beeber, April Panitz, Safa Ibrahim, Marilyn Fraser, Grace Ma, Khursheed Navder, Ming-Chin Yeh, Olorunseun Ogunwobi
Journal: Cancer Research (2020)

Abstract Nutrition is important for cancer prevention. Previous research has found that socioeconomic factors may affect access to a healthy diet, which may impact the risk of cancer. To investigate this association, we assessed dietary behavior and the urinary concentrations of gallic acid, an antioxidant found in various fruits and vegetables, in racial minorities in New York City. Ninety-one (91) participants were recruited from a senior center in East Harlem, New York City, a racially diverse and underserved community. A National Institute of Health (NIH) - validated diet survey questionnaire was used to collect dietary behavior data. Demographic and cancer information were also collected. All 91 participants completed the survey and forty-five (45) participants provided urine samples for gallic acid analysis. Associations between demographic factors and the intake of certain foods were assessed. Gender differences were significantly associated with dietary behavior and urinary gallic acid concentrations. Female participants had a higher daily intake of fruits compared to male participants (p&amp;lt;0.05). Additionally, female participants had significantly higher urinary gallic acid concentrations compared to male participants (p&amp;lt;0.05). Other associations were also observed. Age was negatively associated with the quantity of french fries/fried potatoes and white potatoes intake (p&amp;lt;0.05), while positively associated with frequency of fruit intake (p&amp;lt;0.05). Furthermore, Asian race was associated with a higher frequency of fruit intake (p&amp;lt;0.05), compared to other races. Among all recruited participants, we collected information on three cancer cases. Compared to non-cancer cases, participants with cancer reported a significantly lower fruit intake quantity (p&amp;lt;0.05). In a multivariate analysis, we observed a significant association between fruit intake quantity and urinary gallic acid concentration (p&amp;lt;0.05) after controlling for income. Our findings suggest that gender differences in dietary behavior and urinary gallic acid concentration may explain some of the gender differences in cancer incidence and prevalence observed in racial minority groups. Citation Format: Cristina Zambrano, Wenyue Lu, Cicely Johnson, Maayan Beeber, April Panitz, Safa Ibrahim, Marilyn Fraser, Grace Ma, Khursheed Navder, Ming-Chin Yeh, Olorunseun Ogunwobi. Gender differences in dietary behavior and urinary gallic acid concentrations in racial minorities in New York City [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 3462.
SAT0046 Evaluation of functional status and quality of life in patients with ankylosing spondylitis
Authors: EE Bostan, P Borman, H Bodur, N Barca
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> The aim of this study was to evaluate the functional status and quality of life and to determine the relationship between disability and clinical variables in a group of patients with ankylosing spondylitis (AS). <h3>Methods</h3> Fifty-one patients with a mean age of 37.2 years were included to the study. Clinical variables including pain by visual analogue scale (VAS), functional indices by Bath ankylosing spondylitis functional index (BASFI), Dutch functional index (DFI) and Dougdas functional index (FI), metrology by Bath ankylosing spondylitis metrology index (BASMI) and disease activity by Bath ankylosing spondylitis disease activity index (BASDAI) were studied. Radiographs of the patients were scored by Bath ankylosing spondylitis radiological index (BASRI) and quality of life was assessed by Nottingham health profile (NHP). Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were also recorded. <h3>Results</h3> The scores of BASMI and BASRI were correlated with disease duration and BASDAI scores. Functional loss assessed by BASFI, DFI and FI were strongly correlated with BASDAI, BASRI and BASMI. Patients with peripheral joint involvement had greater disability. Functional loss was more correlated with the levels of CRP than ESR. NHP scores best correlated with functional indexes followed by BASDAI. <h3>Conclusion</h3> In conclusion, functional loss should be considered in evaluation of AS patients. These functional indexes can help to assess the patients more objectively and monitorize the treatment in order to increase the quality of life in patients suffering from this chronic condition.
Abstract B33: Reproductive factors and risk of ovarian cancer: The Singapore Chinese Health Study
Authors: Ming Lei, Shalkar Adambekov, Renwei Wang, Jianmin Yuan, Samia Lopa, Faina Linkov
Journal: Clinical Cancer Research (2020)

Abstract Background: Ovarian cancer (OC) is the deadliest gynecologic cancer, with varying incidence across geographic regions. Asian population is underrepresented in etiologic and epidemiologic investigations in the area of ovarian cancer. We explored association between ovarian cancer incidence and several lifestyle, dietary, reproductive, and hormonal risk factors in the Singapore Chinese cohort study. Methods: A population of 34,028 Singaporean Chinese women aged 45-74 were enrolled in the Singapore Chinese Health Study between 1993 to 1998, and followed through Dec. 31, 2010. Data on demographics, tobacco use, dietary and reproductive factors were collected. Cases of OC were determined via linkage to Singapore Cancer Registry. Poisson regression model was performed and hazard ratios (HR) and 95% confidence intervals (CI) were estimated for each variable. Established risk factors and variables showing a significant result in univariate analysis were included in the multivariate analysis. Results: 128 cases of OC were identified. No dietary factors were associated with OC incidence in this population, nor was tobacco/alcohol use. In univariate analysis, significant results included later age of menopause (RR=2.38, 95%CI 1.23-4.30), later age of first birth (RR=0.43, 95%CI 0.17-0.93) and longer period of menstruating (RR=1.48, 95%CI 1.02-2.18), parity (RR=0.37, 95%CI 0.22-0.65), and oral contraceptives use (RR=0.54, 95% CI 0.33-0.84). In multivariate analysis, higher number of children was associated with decreased ovarian cancer risk (1-2, 3-4, 5+ vs nulliparity: RR=0.45, 95%CI 0.26-0.8; RR= 0.35, 95%CI 0.20-0.51 RR= 0.32, 95%CI 0.18-0.60, respectively). Conclusions: Parity, contraceptive use, and later age of first birth decreased the risk of OC incidence, while later age at menopause and longer menstruating period increased ovarian cancer risk in Singaporean Chinese cohort. This finding is consistent with findings in Western populations. Future studies are needed to determine risk factors associated with ovarian cancer histologic types and identify markers of elevated risk, especially in Asian populations. Citation Format: Ming Lei, Shalkar Adambekov, Renwei Wang, Jianmin Yuan, Samia Lopa, Faina Linkov. Reproductive factors and risk of ovarian cancer: The Singapore Chinese Health Study [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B33.
Live-attenuated Vaccines Prevent Respiratory Syncytial Virus–associated Illness in Young Children
Authors: Ruth A. Karron, Jessica E. Atwell, Elizabeth J. McFarland, Coleen K. Cunningham, Petronella Muresan, Charlotte Perlowski, Jennifer Libous, Stephen A. Spector, Ram Yogev, Mariam Aziz, Suzanne Woods, Kimberli Wanionek, Peter L. Collins, Ursula J. Buchholz
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Active immunization is needed to protect infants and young children against respiratory syncytial virus (RSV). Rationally designed live-attenuated RSV vaccines are in clinical development.
Abstract A02: The feedback loop among miR-449b-3p/ADAM17/NF-κB promotes metastasis in nasopharyngeal carcinoma
Authors: Qian Fei, Ming-Yu Du, Ning Jiang, Li Yin, Xia He
Journal: Clinical Cancer Research (2020)

Abstract Emerging pieces of evidence have proved an important role of miRNAs in tumorigenesis and progression. However, the function of miRNAs in nasopharyngeal carcinoma (NPC) development remains poorly elucidated. Quantitative reverse transcription-polymerase chain was used to detect the expression level of miR-449b-3p in NPC cell lines and tissues. We performed cell viability assay, colony formation, flow cytometric, transwell assay, and wound-healing assay to assess the ability of cell proliferation, apoptosis, invasion, and migration in vitro, respectively. NPC xenograft tumor and lymph node metastatic mice model were conducted to validate the function of miR-449b-3p in vivo. Luciferase reporter assay, ChIP assay, and Western blot analysis were actualized to explore the mechanism underlying the miR-449b-3p on NPC metastasis. Here we showed that miR-449b-3p was downregulated in NPC specimens (p&amp;lt;0.001) and cells (p&amp;lt;0.05), and most of the patients with advanced-stage NPC had an impaired expression of miR-449b-3p, on the contrary, early-stage NPC patients had a high level of miR-449b-3p (p&amp;lt;0.001). Moreover, miR-449b-3p inhibited NPC metastasis both in vitro and in vivo. Further investigation revealed that a disintegrin and metalloproteinase 17 (ADAM17) was the direct target of miR-449b-3p. Rescue experiments suggested that the downregulation of ADAM17 in miR-449b-3p inhibited cells partially reversed the inhibition of cell invasion and migration. We also found that ADAM17 could conversely suppress the promoter activity and expression of miR-449b-3p via inducing NF-κB transcriptional activity. In conclusion, our study provides new insights into the mechanism underlying the invasion and metastasis in NPC. The novel miR-449b-3p/ADAM17/NF-κB feedback loop in NPC could potentially be a target for clinical treatment in NPC. Citation Format: Qian Fei, Ming-Yu Du, Ning Jiang, Li Yin, Xia He. The feedback loop among miR-449b-3p/ADAM17/NF-κB promotes metastasis in nasopharyngeal 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 A02.
Abstract PR10: High-throughput functional and multi-omic single-cell characterization to elucidate ovarian intratumor and microenvironmental heterogeneity
Authors: Kristin G. Beaumont, Austin Hake, Ying-Chih Wang, Hardik Shah, Kimaada Allette, Wissam Hamou, Arpit Dave, Christina Andreou, Maya Strahl, Hanane Arib, Alesia Antoine, Ethan Ellis, Melissa Smith, Peter Dottino, John Martignetti, Eric E. Schadt, Robert P. Sebra
Journal: Clinical Cancer Research (2020)

Abstract The genetic and functional complexity of bulk tumor tissue and its associated microenvironment, comprising heterogeneous cellular clones, has become more evident due to rapid advances in single-cell and deep-sequencing technologies. In this research, we present methods to better characterize clonal diversity from patient-derived cell lines and tumor biopsies at the single-cell level. We will profile intratumor and microenvironmental heterogeneity through single-cell selection, single-cell DNA and RNA sequencing, and real-time functional data. In addition to genetic data, single-cell real-time growth dynamics alongside CA125 secretion will be discussed as real-time functional assays. This approach uses bulk or discriminate selection of cells based on phenotype across a broad range of cellular inputs. Targeted cells from the tumor and its microenvironment were manipulated using light-induced dielectrophoresis into holding areas on the BLI Beacon platform for single-cell isolation and/or culture for monitoring growth kinetics and conducting functional screening. Hundreds to thousands of independent cells or batches were selected from resected tumor and adjacent tissue; genomic DNA was amplified and characterized using Ion Torrent AmpliSeq targeted panels and/or MissionBio Tapestri scDNA-Seq. Collectively this genomic data were used to identify cellular clonality and better address the degree of clonal heterogeneity across these tumors when compared to bulk sequencing. Specifically, growth kinetics, differential expression, and TP53 mutation profiling will be discussed in the context of several pilot primary tumor-derived samples. Orthogonal RNA-Seq data obtained using 1,500-5,000 cells per sample for 3’ mRNA scRNA-Seq on the 10X Genomics Chromium platform will also be discussed. Through the integration of these technologies, we hope to showcase an efficient and comprehensive method for assessing intratumor and microenvironmental heterogeneity. This abstract is also being presented as Poster B53. Citation Format: Kristin G. Beaumont, Austin Hake, Ying-Chih Wang, Hardik Shah, Kimaada Allette, Wissam Hamou, Arpit Dave, Christina Andreou, Maya Strahl, Hanane Arib, Alesia Antoine, Ethan Ellis, Melissa Smith, Peter Dottino, John Martignetti, Eric E. Schadt, Robert P. Sebra. High-throughput functional and multi-omic single-cell characterization to elucidate ovarian intratumor and microenvironmental heterogeneity [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr PR10.
Brain transforms natural killer cells that exacerbate brain edema after intracerebral hemorrhage
Authors: Zhiguo Li, Minshu Li, Samuel X. Shi, Nan Yao, Xiaojing Cheng, Ai Guo, Zilong Zhu, Xiaoan Zhang, Qiang Liu
Journal: The Journal of Experimental Medicine (2020)

Perihematomal edema (PHE) occurs within hours after intracerebral hemorrhage (ICH), leading to secondary injury manifested by impaired blood–brain barrier (BBB) integrity and destruction of adjacent tissue. To dissect the mechanisms underlying PHE formation, we profiled human and mouse perihematomal tissues and identified natural killer (NK) cells as the predominant immune cell subset that outnumbers other infiltrating immune cell types during early stages of ICH. Unbiased clustering of single-cell transcriptional profiles revealed two major NK cell subsets that respectively possess high cytotoxicity or robust chemokine production features in the brain after ICH, distinguishing them from NK cells of the periphery. NK cells exacerbate BBB disruption and brain edema after ICH via cytotoxicity toward cerebral endothelial cells and recruitment of neutrophils that augment focal inflammation. Thus, brain-bound NK cells acquire new features that contribute to PHE formation and neurological deterioration following ICH.
Abstract B13: Utilizing metabolic reprogramming to regulate fibroblast phenotype and reduce radiation fibrosis
Authors: Xiao Zhao, Pamela Psarianos, David Goldstein, Ralph Gilbert, Ian Witterick, Laurie Ailles, Benjamin Haibe-Kains, Fei-Fei Liu
Journal: Clinical Cancer Research (2020)

Abstract Introduction: Radiation fibrosis affects up to half of all patients undergoing radiotherapy for head and neck cancer treatment. It is characterized by excess extracellular matrix deposition, leading to tissue dysfunction, distortion, hardening, and pain. There are currently no effective treatments for radiation fibrosis. A fundamental challenge has been to understand and modulate the function of fibroblasts, a key mediator in extracellular matrix production and degradation. Recent evidence has demonstrated that metabolic regulation plays an important role in altering cell behavior in cancer biology and immunology. However, little is known about how metabolic changes affect fibroblast phenotype. Hypothesis: We propose that metabolic reprogramming may be an effective strategy to modulate fibroblast function and reduce radiation fibrosis. Results: An interplay between fatty acid oxidation and glycolysis was found to be a convergence point directly governing fibroblast behavior. It was demonstrated that manipulating the balance between FAO and glycolysis in fibroblasts induced either an extracellular matrix anabolic or catabolic phenotype. Specifically, anabolic fibroblasts relied on a fatty acid oxidation to glycolysis shift to produce extracellular matrix components. Reversal of this metabolic shift generated a catabolic fibroblast, which downregulated extracellular matrix synthesis and upregulated extracellular matrix lysosomal degradation. We further uncovered that CD36, a multifunctional fatty acid transporter, was a crucial link connecting fibroblast metabolism with extracellular matrix regulation, as its depletion completely inhibited collagen-1 internalization and degradation. Finally, through metabolic reprogramming using fibroblasts expressing high levels of CD36, but not CD36 knockout fibroblasts, metabolic balance could be restored, and in turn extracellular matrix accumulation was reduced in murine radiation fibrosis. Conclusions: We have uncovered that a fibroblast’s phenotype can be differentiated and regulated based on its metabolic signature. These findings have significant implications for drug development and for future cellular therapies to reduce radiation fibrosis. Citation Format: Xiao Zhao, Pamela Psarianos, David Goldstein, Ralph Gilbert, Ian Witterick, Laurie Ailles, Benjamin Haibe-Kains, Fei-Fei Liu. Utilizing metabolic reprogramming to regulate fibroblast phenotype and reduce radiation fibrosis [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 B13.