tbuckley/cabot-search huggingface dataset:
Abstract 3341: Rural and urban disparities in colonoscopy use persisted despite cost-sharing reduction among Medicare beneficiaries
Authors: Min Jee Lee, Wiley Jenkins, Eric Adjei Boakye, Sabha Ganai
Journal: Cancer Research (2019)

Abstract Background: Due to passage of the Patient Protection and Affordable Care Act (ACA), Medicare began waiving Part B deductibles and eliminating coinsurance for all colonoscopies in 2011. As rural populations have significantly lower income than urban, there is hope the cost reduction would decrease rural screening disparities. We thus examined rural-urban colonoscopy use pre-/post-ACA implementation. Methods: We used Behavioral Risk Factor Surveillance System data (2008-2016) to examine colonoscopy utilization for two years pre-ACA (2008 and 2010) and three years post-ACA (2012, 2014, and 2016) with stratification by rural/urban residence. Multivariate logistic regression was used to examine the differences in screening likelihood across rural and urban groups, while controlling for other factors such as age, sex, marital status, race/ethnicity, household income, educational attainment, gastroenterologist availability, exercise, smoking, and years. Results: Of the 302,941 eligible Medicare beneficiaries, 203,426 (67.2%) received a colonoscopy. Colonoscopy receipt increased from 62.8% pre-ACA to 70.2% post-ACA years (p&amp;lt;.001). Across rural-urban areas, we found a significant increase in the receipt of colonoscopy from pre- to post-ACA (p&amp;lt;.001). The receipt of colonoscopy was higher among urban residents (69.2%) compared to rural residents (63.5%, p&amp;lt;.001). After adjusting for covariates, urban residents were more likely to receive colonoscopy both pre-ACA (OR=1.11, 95% CI: 1.06-1.15) and post-ACA (OR=1.11, 95% CI: 1.06-1.16). Conclusions: Despite cost-sharing reduction of Medicare coverage for colonoscopy, rural and urban differences in colonoscopy use persisted over time among Medicare beneficiaries. Although the receipt of colonoscopy increased over time, the gap between rural and urban populations has remained. Colonoscopy Use Before and After Implementation of The ACAPreACAPost ACARuality%OR95%CI%OR95%CIRural59.4166.61Urban64.91.111.061.1572.11.111.061.16 Citation Format: Min Jee Lee, Wiley Jenkins, Eric Adjei Boakye, Sabha Ganai. Rural and urban disparities in colonoscopy use persisted despite cost-sharing reduction among Medicare beneficiaries [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 3341.
Abstract 1223: Somatic mutations in collagens impact patient outcomes in cancer
Authors: Alexander S. Brodsky, Jay Khurana, Dongfang Yang, Ece Gamsiz, Ian Wong, Murray Resnick
Journal: Cancer Research (2019)

Abstract Stomach cancer remains among the most lethal diseases around the world demanding improved treatments. The tumor microenvironment (TME) is a critical driver of tumor progression and response to therapy and mediates many of the cancer hallmarks. Collagens are major components of the TME that controls disease progression and mediate therapeutic response. Collagens have been associated with stiffening of the tumor stroma, malignancy and therapeutic resistance. Collagenopathies are caused by loss of function collagen mutations that disrupt tissue formation and are dominant negative variants. We have found somatic tumor variants in collagens that are similar loss-of-function mutations as the germline variants observed in collagenopathies, providing guidance to interpret these cancer mutations. Indeed, the role of somatic mutations in collagens has not been addressed. Remarkably, we found multiple independent lines of evidence that collagen variants impact stomach adenocarcinoma tumors, consistent with a model that collagen variants disrupt the extracellular matrix (ECM) leading to improved therapeutic responses. 1) We find that loss-of-function collagen missense and nonsense mutations are associated with improved survival and disease-free progression times in gastric tumors in the TCGA dataset. 2) The same type of mutations observed in cancer are known to cause rare human diseases and therefore have the potential to impact cell function. 3) Independent of the patient outcome data, collagen variants were associated with significant changes in expression of tumor environment factors including ECM glycoproteins and EMT expression signatures. 4) Remapping RNA-seq reads reveals that single nucleotide variants of the collagens, matching the exome sequencing data are expressed. We will present computational and functional data supporting the hypothesis that somatic variants impact gastric tumors as well as analysis of the impact of collagens somatic mutations PanCancer. Somatic mutations in collagens represent a new paradigm for how cancer cells mediate the TME providing new biomarker and therapeutic opportunities to disrupt the ECM and improve outcomes for cancer patients. Citation Format: Alexander S. Brodsky, Jay Khurana, Dongfang Yang, Ece Gamsiz, Ian Wong, Murray Resnick. Somatic mutations in collagens impact patient outcomes in 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 1223.
Quality of life assessment and reporting in colorectal cancer: a systematic review of phase 3 trials published between 2012 and 2018
Authors: P. Lombardi, L. Marandino, E. De Luca, C. Zichi, D. Pignataro, R. Di Stefano, E. Ghisoni, A. Mariniello, M. Reale, E. Trevisi, L. Gianmarco, L. Muratori, A. La Salvia, C. Sonetto, F. Leone, M. Aglietta, S. Novello, G. Scagliotti, F. Perrone, M. Di Maio
Journal: Annals of Oncology (2019)
Multi-dimensional analysis identified rheumatoid arthritis-driving pathway in human T cell
Authors: Masaru Takeshita, Katsuya Suzuki, Yasushi Kondo, Rimpei Morita, Yuumi Okuzono, Keiko Koga, Yoshiaki Kassai, Kanae Gamo, Maiko Takiguchi, Rina Kurisu, Hideyuki Mototani, Yukihiko Ebisuno, Akihiko Yoshimura, Tsutomu Takeuchi
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Objectives</h3> Rheumatoid arthritis (RA) is an autoimmune disease accompanied by lymphocyte infiltration into joint synovium. While T cells are considered to be important for its pathogenesis, the features that are the most relevant to disease and how they change after treatment remain unclear. The aim of this study was to clarify the characteristics of T cells in RA, comprehensively. <h3>Methods</h3> We enrolled a total of 311 patients with RA and 73 healthy participants, and carefully classified them by disease state, constructed multiple cohorts and analysed clinical samples from them in a stepwise manner. We performed immunophenotyping with multiple evaluation axes, and two independent transcriptome analyses complementary to each other. <h3>Results</h3> We identified that 'effector memory-Tfh' subset was specifically expanded in the peripheral blood (PB) of patients with RA in correlation with disease activity, and reverted after treatment. Besides, we revealed distinct features of T cells in synovial fluid (SF) that the expression of Tfh/Tph-related genes and pro-inflammatory cytokines and chemokines, including <i>CXCL13</i>, were significantly enriched, whereas these phenotype were Th1-like. Finally, we identified specific pathways, such as mTORC1, IL-2-stat5, E2F, cell cycle and interferon-related genes, that were significantly enriched in SF, in particular, as well as PB of untreated patients with RA, and notably, these features reverted after treatment. <h3>Conclusion</h3> Our multi-dimensional investigation identified disease relevant T-cell subsets and gene signatures deeply involved in pathogenesis of RA. These findings could aid in our understanding of essential roles of T cells in RA and will facilitate to development better diagnostic and therapeutic interventions.
Abstract 2173: Developing a high-throughput, high content screening technology to identify new anticancer drug treatments
Authors: Andrew T. Milcarek, Kevin Daus, Mary L. Alpaugh
Journal: Cancer Research (2019)

Abstract The high attrition rate of new chemotherapeutic drugs represents the single most important challenge in anticancer drug development. With only one drug out of 10, 000 test compounds gaining FDA-approval, attrition is often attributed to failure of in vitro drug efficacy to translate to clinical success. The overall drug discovery and development pipeline can be dramatically improved with new, innovative assays of high pharmacological relevance that can shorten the discovery/preclinical phase and ensure rapid translation to clinic. We report the development of a three-dimensional phenotypic drug screening platform based on spheroidsMARY-X. The tight, compact spheroidsMARY-X form spontaneously due to innate molecular determinants with proliferative cells on the outer periphery and a dormant tumor cell core. These features mimic the intratumoral biological complexities of tumor tissue and thus provide a relevant in vitro model for drug discovery with a high degree of predictive value. Significantly, this model allows analysis of drug targeting of dormant tumor cells, the difficult to treat resistant or highly refractory cell population. Drug response can be reliably assessed using brightfield microscopy and can be quantified by measuring spheroid circularity (i.e., dissolution index). Evaluation of soluble factor concentration is performed using molecular rotors through restricted intramolecular rotation upon protein binding with a subsequent quantum yield. Overall, we present a 3-dimensional anticancer assay that provides a rapid, efficient, relevant platform for the evaluation of drug response and allows identification of small molecule hits in both proliferative and more importantly, dormant tumor cells, the major cause of relapse and recurrent metastatic disease. Citation Format: Andrew T. Milcarek, Kevin Daus, Mary L. Alpaugh. Developing a high-throughput, high content screening technology to identify new anticancer drug treatments [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 2173.
Emerging concepts and challenges in implementing the exposome paradigm in allergic diseases and asthma.
Authors: Ioana Agache, Rachel L. Miller, James E. Gern, Peter W. Hellings, Marek Jutel, Antonella Muraro, Wanda Phipatanakul, Santiago Quirce, David Peden
Journal: Allergy (2018)

Exposome research can improve the understanding of the mechanistic connections between exposures and health to help mitigate adverse health outcomes across the life span. The exposomic approach provides a risk profile instead of single predictors and thus is particularly applicable to allergic diseases and asthma. Under the PRACTALL collaboration between the European Academy of Allergy and Clinical Immunology (EAACI) and the American Academy of Allergy, Asthma, and Immunology (AAAAI), we evaluated the current concepts and the unmet needs on the role of the exposome in allergic diseases and asthma.
Genome-Wide CRISPR-Cas9 Screening Reveals a Role for TRAF2 in Resistance to IMiDs in Multiple Myeloma
Authors: Jiye Liu, Wenrong Zhou, Lijie Xing, Liang Lin, Kenneth Wen, Yu-Tzu Tai, Teru Hideshima, Yong Cang, Kenneth C. Anderson
Journal: Blood (2018)
A Connective Tissue Mast-Cell-Specific Receptor Detects Bacterial Quorum-Sensing Molecules and Mediates Antibacterial Immunity
Authors: Priyanka Pundir, Rui Liu, Chirag Vasavda, Nadine Serhan, Nathachit Limjunyawong, Rebecca Yee, Yingzhuan Zhan, Xintong Dong, Xueqing Wu, Ying Zhang, Solomon H. Snyder, Nicolas Gaudenzio, Jorge E. Vidal, Xinzhong Dong
Journal: Cell Host & Microbe (2019)
FGFR3 Mutations Are an Adverse Prognostic Factor in Patients with t(4;14)(p16;q32) Multiple Myeloma: An Mmrf Commpass Analysis
Authors: Brooks Benard, Austin Christofferson, Christophe Legendre, Jessica Aldrich, Sara Nasser, Jennifer Yesil, Daniel Auclair, Winnie Liang, Sagar Lonial, Jonathan J. Keats
Journal: Blood (2017)
Abstract 20363: Dosage-Sensitive Candidate Genes for Bicuspid Aortic Valve Cause Outflow Tract Defects in Zebrafish
Authors: Alexandra L Janda, Limin Gong, Siddharth K Prakash
Journal: Circulation (2017)

Introduction: Bicuspid aortic valve (BAV) is the most common adult congenital heart defect and is 30 times more prevalent in Turner Syndrome (TS). The genetic causes of BAV are mostly unknown. We p...
Abstract 1578: Cohesin complex-related genes in colorectal cancer
Authors: Masaru Sasaki, Norikatsu Miyoshi, Kazuhiro Saso, Shiki Fujino, Hidekazu Takahashi, Naotsugu Haraguchi, Chu Matsuda, Taishi Hata, Hirofumi Yamamoto, Tsunekazu Mizushima, Masaki Mori, Yuichiro Doki
Journal: Cancer Research (2019)

Abstract Backgrounds: One of the hallmarks of cancer is chromosomal instability and it leads to aneuploidy. Defective sister chromatid cohesion represents a major cause of chromosome instability in human cancers. Stromal antigen (STAG) encodes a subunit of the cohesin complex, which regulates cohesion and segregation of sister chromatids. STAG contains STAG1, STAG2 related to somatic division and STAG3 related to meiosis. We evaluated the relationship between STAG and colorectal cancer. Materials and methods: We examined STAG mRNA expression in tumor tissues by real-time qPCR. The samples were obtained from 172 colorectal cancer patients who underwent curative resection from November 2009 to December 2013 at the Osaka International Cancer Institute, Japan. STAG mRNA expression was evaluated by comparing with clinicopathological features and patients’ survival. Patients were classified into a high STAG expression and low STAG expression groups. Kaplan-Meier survival curves were evaluated using the log-rank test. The association with STAG expression and prognosis was analyzed by the Cox proportional regression model. Then, we utilized siRNA to knock down the expression of STAG3 and examined whether this altered proliferation in colorectal cancer cell lines (HCT116, RKO, HT29 and SW480). Results: STAG1 and STAG2 did not show no statistically significant differences in disease-free survival (DFS) and overall survival (OS). In contrast, DFS rate was significantly lower in the high STAG3 expression group than the low STAG3 expression group (P = 0.032). A multivariate analysis showed that the high STAG3 mRNA expression was a significant independent risk factor for the recurrence (P = 0.006). In patients with adjuvant chemotherapy, the high STAG3 expression group was significantly worse for DFS (P = 0.043) and OS (P = 0.020), compared to the low STAG3 expression group. However, the proliferation assays evaluating the knockdown of STAG3 did not show any significant differences. Conclusions: Our study showed that STAG3 can be a novel prognostic biomarker and the high STAG3 mRNA expression was an independent risk factor for the recurrence, suggesting that it relates to the chemotherapy resistance in colorectal cancer. We perform some other assays to evaluate the biology (focusing on the cancer invasiveness, the drug sensitivity, etc.) which reveal the mechanism of STAG3 in colorectal cancer. Citation Format: Masaru Sasaki, Norikatsu Miyoshi, Kazuhiro Saso, Shiki Fujino, Hidekazu Takahashi, Naotsugu Haraguchi, Chu Matsuda, Taishi Hata, Hirofumi Yamamoto, Tsunekazu Mizushima, Masaki Mori, Yuichiro Doki. Cohesin complex-related genes in colorectal 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 1578.
Abstract 13644: Functionally Competent Cardiac Stem Cells can be Isolated From Patients Using Endomyocardial Biopsies
Authors: Domenico D’Amario, Antonio M Leone, Costantino Smaldone, Maria L Narducci, Gemma Pelargonio, Frediano Inzani, Antonia Camporeale, Rosaria Santangelo, Antonio Iaconelli, Melissa Manchi, Anna Severino, Maurizio Sanguinetti, Andrea Siracusano, Lara Maria Clara Ottaviani, Massimo Massetti, Filippo Crea
Journal: Circulation (2013)

Intracoronary infusion of Cardiac Stem Cells (CSCs) isolated from right atrial appendage, resected during CABG is effective in improving left ventricular systolic function and reducing infarct size...
Racial Comparisons in Timeliness of Colon Cancer Treatment in an Equal-Access Health System
Authors: Yvonne L Eaglehouse, Matthew W Georg, Craig D Shriver, Kangmin Zhu
Journal: JNCI Journal of the National Cancer Institute (2019)

Non-Hispanic black (NHB) adults with cancer may have longer time-to-treatment than non-Hispanic whites (NHW) in the United States. Unequal access to medical care may partially account for this racial disparity. This study aimed to investigate whether there were racial differences in time-to-treatment and in treatment delays for patients diagnosed with colon cancer in the equal-access Military Health System (MHS).
Abstract 1239: Structure activity relationship of alexidine analogs for the inhibition of collective invasion
Authors: Jamie Arnst, Rachel Commander, Adam Marcus
Journal: Cancer Research (2019)

Abstract Lung cancer is the leading cause of cancer-related deaths in the US with an overall 5-year survival of only 15-20%. Metastatic disease is a major contributor to poor survival and novel therapeutics that can selectively target invasive tumor cell populations are lacking. Metabolic reprogramming contributes to tumor progression with effective therapies targeting cancer metabolism available. However, it remains unclear whether targeting cancer metabolism will prove valuable in inhibiting invasive cancer populations. Recent studies have demonstrated anticancer activity by the mitochondria-targeting bioactive small molecule alexidine dihydrochloride. Our group has previously found that alexidine specifically inhibits the a highly invasive subpopulation of H1299 previous identified in our lab by decoupling and decreasing collective invasion. Here we report the structure activity relationship (SAR) between analogs of alexidine on the inhibition of collective invasion in NSCLC cell lines. For these studies, we utilized an in vitro 3D invasion model where NSCLC cell lines were allowed to form spheroids, and then were embedded into Matrigel and allowed to invade over 48h in the presence or absence of the analogs. Using this technique, we identified two novel alexidine analogs with improved efficacy at inhibiting the invasion of H1299 NSCLC cells. Additionally, we examined the phosphorylation of pyruvate dehydrogenase (PDH), the gatekeeper for the entrance of pyruvate into the TCA cycle, following treatment with the alexidine analogs. We observed a significant correlation between PDH phosphorylation and inhibition of invasion following treatment with the analogs. In conclusion, we have identified two novel alexidine analogs with improved inhibition of invasion in NSCLC cell lines in an in vitro model. Citation Format: Jamie Arnst, Rachel Commander, Adam Marcus. Structure activity relationship of alexidine analogs for the inhibition of collective invasion [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 1239.
Abstract 4872: Disulfiam, a re-positioned aldehyde dehydrogenase inhibitor, enhances radiosensitivity of human glioblastoma cells <i>in vitro</i>
Authors: Hyeon Kang Koh, Soo Yeon Seo, Jin Ho Kim, Hak Jae Kim, Eui Kyu Chie, Seung-Ki Kim, Il Han Kim
Journal: Cancer Research (2019)

Abstract Purpose : Glioblastoma, the most common brain tumor in adults, has poor prognosis. The purpose of this study was to determine the effect of disulfiram (DSF), an aldehyde dehydrogenase inhibitor, on in vitro radiosensitivity of glioblastoma cells with different methylation status of O6-methylguanine-DNA methyltransferase (MGMT) promoter and the underlying mechanism of such effect. Materials and Methods : Five human glioblastoma cells (U138MG, T98G, U251MG, U87MG, and U373MG) and one normal human astrocyte (NHA) cell were cultured and treated with DSF or 6MV x-rays (0, 2, 4, 6, 8 Gy). For combined treatment, cells were treated with DSF before irradiation. Surviving fractions fit from cell survival based on colony forming ability. Apoptosis, DNA damage repair, and cell cycle distribution were assayed by Western blot for cleaved caspase-3, γH2AX staining, and flow cytometry, respectively. Results : DSF induced radiosensitization in most of the glioblastoma cells, especially, in the cells with radioresistance as wildtype unmethylated promoter (MGMT-wt), but did not in normal NHA cell. DSF augmented or induced cleavage of caspase-3 in all cells after irradiation. DSF inhibited repair of radiation-induced DNA damage in MGMT-wt cells, but not in cells with methylated MGMT promoter (MGMT-meth). DSF abrogated radiation-induced G2/M arrest in T98G and U251MG cells. Conclusion : Radiosensitivity of glioblastoma cells were preferentially enhanced by pre-irradiation DSF treatment compared to normal cell, especially radioresistant cells such as MGMT-wt cells. Induction of apoptosis or inhibition of DNA damage repair may underlie DSF-induced radiosensitization. Clinical benefit of combining DSF with radiotherapy should be investigated in the future. Citation Format: Hyeon Kang Koh, Soo Yeon Seo, Jin Ho Kim, Hak Jae Kim, Eui Kyu Chie, Seung-Ki Kim, Il Han Kim. Disulfiam, a re-positioned aldehyde dehydrogenase inhibitor, enhances radiosensitivity of human glioblastoma cells in vitro [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 4872.