tbuckley/cabot-search huggingface dataset:
Comorbid obesity and history of diabetes are independently associated with poorer treatment response to biologics at 6 months: A prospective analysis in Corrona Psoriasis Registry
Authors: Clinton W. Enos, Vanessa L. Ramos, Robert R. McLean, Tin-Chi Lin, Nicole Foster, Blessing Dube, Abby S. Van Voorhees
Journal: Journal of the American Academy of Dermatology (2021)
Is presence of vena caval thrombosis in primary tumor associated with worsened outcomes in metastatic renal cell carcinoma: Analysis of the REMARCC registry
Authors: M.F. Meagher, M. Mir, G. Rebez, R. Autorino, R. Campi, A. Minervini, M. Kriegmair, E. Linares, V. Hevia, M. Musquera, M. D’Anna, E. Rousel, M. Albersen, N. Pavan, F. Claps, A. Antonelli, M. Marchioni, S. Erdem, N. Paksoy, I. Derweesh
Journal: European Urology (2021)
Abstract 748: Conjugated primary bile acids as a biomarker for hepatocellular carcinoma risk in two prospective cohorts
Authors: Claire Elizabeth Thomas, Hung Luu, Renwei Wang, Guoxiang Xie, Jennifer Adams-Haduch, Aizhen Jin, Woon-Puay Koh, Wei Jia, Jaideep Behari, Jian-Min Yuan
Journal: Cancer Research (2021)

Abstract Background: Incidence rates of hepatocellular carcinoma (HCC) has been increasing for several decades in the U.S. Non-alcoholic liver disease (NAFLD) increasingly plays a role in the rising rate of HCC. Experimental data have shown that bile acids, which play key roles in the host-gut microbiota co-metabolism, contribute to the development of NAFLD and HCC. We propose to comprehensively examine the associations of bile acids with risk of HCC in two cohorts. Methods: Thirty-five bile acids were quantified using the state-of-the-art ultraperformance liquid chromatography triple-quadrupole mass spectrometry assays in serum samples collected, on average, five years prior to diagnosis of 197 HCC and the same number of individually matched controls from the Singapore Chinese Health Study and the Shanghai Cohort Study. Conditional logistic regression was used to assess the associations for major bile acids and their conjugates, and bile acid ratios with the risk of HCC. Results: Total primary bile acids were significantly elevated whereas the ratio of secondary bile acids over primary bile acids were significantly lower in HCC cases than controls in both cohorts (P's ≤ 0.001). Doubling of tauro- vs. glyco-conjugates of all bile acids, primary bile acids, and specifically chenodeoycholic acid resulted in an increase in HCC risk of 44, 48, and 34% (P = 0.004, &amp;lt;0.001, 0.001) respectively after adjustment for potential confounders. Conclusion: Primary bile acids, especially tauro-conjugated bile acids were strongly associated with increased risk of HCC risk whereas the secondary vs. primary bile acids ratios were associated with decreased risk of HCC. Citation Format: Claire Elizabeth Thomas, Hung Luu, Renwei Wang, Guoxiang Xie, Jennifer Adams-Haduch, Aizhen Jin, Woon-Puay Koh, Wei Jia, Jaideep Behari, Jian-Min Yuan. Conjugated primary bile acids as a biomarker for hepatocellular carcinoma risk in two prospective cohorts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 748.
Abstract 395: Prediction of genomic based drug sensitivity signatures to enable optimal drug positioning
Authors: Coryandar Gilvary, Olivier Elemento, Neel Madhukar
Journal: Cancer Research (2021)

Abstract Cancer by nature, is a heterogeneous disease, which can lead to highly variable patient responses for targeted therapies - even within the same clinically defined cancer type or subtype. Identifying drug sensitivity biomarkers, patient specific traits that are highly correlated with positive response, has proven to be an effective strategy to identify positioning opportunities and selecting patients. Here, we describe our biomarker identification workflow which identifies drug specific genomic sensitivity signatures, a collection of genomic aberrations that are found to be predictive of patient response, which can be used for patient selection as well as understanding a compound's mechanism of action. Using available drug efficacy data (in vitro or in vivo results) with paired baseline genomics data, we build diverse models to predict sample sensitivity to a drug. For every model, we train and measure the performance and how each genomic aberration contributes to model performance, those that do not sufficiently increase predictability are removed. This process is repeated, with each new model training on a smaller subset of genomic aberrations, until we have the minimum number of genomic aberrations needed to reach peak predictive performance. The resulting set of genomic aberrations make up a genomic sensitivity signature. Instead of using one type of algorithm to build these models, we train three distinct model types: linear, decision tree and custom kernel based. The multiple model architecture allows us to model the unique underlying biological mechanism of a compound's efficacy, such as synthetic lethal relationships or resistant pathway deactivation, ultimately giving us a collection of robust biomarker signatures. In addition to mechanistic understanding, clinical feasibility was a top priority. Therefore, our workflow architecture has been tested and validated to incorporate mutation, copy number alteration and/or gene expression based biomarkers either in combination or alone. This flexibility lowers the data required to use our workflow, making it more widely available to investigational drugs. Our identification of genomic sensitivity signatures can then be used for clinical patient selection or positioning a compound for a clinically defined cancer type, based on the prevalence of the predicted signature. Overall, this workflow is a powerful approach identifying diverse, mechanism based drug sensitivity signatures that can enable identifying the right patient for a therapy of interest. Citation Format: Coryandar Gilvary, Olivier Elemento, Neel Madhukar. Prediction of genomic based drug sensitivity signatures to enable optimal drug positioning [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 395.
Assessing comprehensive surgical outcomes of Freyer, Millin and Madigan robot assisted simple prostatectomy: Trifecta and pentafecta outcomes
Authors: A.M. Bove, A. Brassetti, U. Anceschi, G. Tuderti, L. Misuraca, M. Ferriero, R. Mastroianni, S. Guaglianone, C. Gerolimetto, S. Cartolano, C. Leonardo, M. Gallucci, G. Simone
Journal: European Urology (2021)
De-Escalation of Dual Antiplatelet Therapy in Patients With Acute Coronary Syndromes
Authors: Satoshi Shoji, Toshiki Kuno, Tomohiro Fujisaki, Hisato Takagi, Alexandros Briasoulis, Pierre Deharo, Thomas Cuisset, Azeem Latib, Shun Kohsaka
Journal: Journal of the American College of Cardiology (2021)
Abstract LB241: Genomic and molecular features of metachronous metastasis in clear cell renal cell carcinoma
Authors: Marjan Mojtabavi Naeini, Neha Rohatgi, Umesh Ghoshdastider, Ari A. Hakimi, Anders Jacobsen Skanderup
Journal: Cancer Research (2021)

Abstract Molecular features associated with risk of metachronous metastases (MM) in clear cell renal cell carcinoma (ccRCC) are poorly defined. Here, we performed systematic genomic and molecular analysis of 192 ccRCC primary tumors with extended clinical follow-up for development of MM. Whole-exome sequencing analysis revealed no association between somatic mutations and development of MM. However, chromosomal deletions at 1p33 were more prevalent in tumors that later progressed with MM. We inferred immune cell infiltrates and found that depletion of regulatory T cells and M1 macrophages were associated with development of MM. Next, we used bulk tumor transcriptome deconvolution to estimate cancer (malignant) and stromal (non-malignant) cell gene expression differences between MM and indolent primary tumors. Downregulation of the Crumbs complex component PATJ (1p31) in cancer cells of MM tumors suggested loss of apicobasal cell polarity as a risk factor in metastatic progression. We also identified downregulation of fatty acid degradation in cancer cells of MM tumors. Overall, our results nominate novel genomic and molecular features underpinning metachronous metastasis in ccRCC. Citation Format: Marjan Mojtabavi Naeini, Neha Rohatgi, Umesh Ghoshdastider, Ari A. Hakimi, Anders Jacobsen Skanderup. Genomic and molecular features of metachronous metastasis in clear cell renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB241.
Influence of DM-sensitivity on immunogenicity of MHC class II restricted antigens
Authors: Anna Luise Bernhardt, Julia Zeun, Miriam Marecek, Hannah Reimann, Sascha Kretschmann, Judith Bausenwein, Edith D van der Meijden, Margarete M Karg, Tabea Haug, Lisa Meintker, Gloria Lutzny-Geier, Andreas Mackensen, Anita N Kremer
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Graft-versus-host-disease (GvHD) is a major problem in allogeneic stem cell transplantation. We previously described two types of endogenous human leukocyte antigen (HLA)-II restricted antigens depending on their behavior towards HLA-DM. While DM-resistant antigens are presented in the presence of HLA-DM, DM-sensitive antigens rely on the expression of HLA-DO-the natural inhibitor of HLA-DM. Since expression of HLA-DO is not upregulated by inflammatory cytokines, DM-sensitive antigens cannot be presented on non-hematopoietic tissues even under inflammatory conditions. Therefore, usage of CD4+ T cells directed against DM-sensitive antigens might allow induction of graft-versus-leukemia effect without GvHD. As DM-sensitivity is likely linked to low affinity peptides, it remains elusive whether DM-sensitive antigens are inferior in their immunogenicity. Methods We created an in vivo system using a DM-sensitive and a DM-resistant variant of the same antigen. First, we generated murine cell lines overexpressing either H2-M or H2-O (murine HLA-DM and HLA-DO) to assign the two model antigens ovalbumin (OVA) and DBY to their category. Further, we introduced mutations within the two T-cell epitopes and tested the effect on DM-sensitivity or DM-resistance. Furthermore, we vaccinated C57BL/6 mice with either variant of the epitope and measured expansion and reactivity of OVA-specific and DBY-specific CD4+ T cells. Results By testing T-cell recognition of OVA and DBY on a murine B-cell line overexpressing H2-M and H2-O, respectively, we showed that OVA leads to a stronger T-cell activation in the presence of H2-O demonstrating its DM-sensitivity. In contrast, the DBY epitope does not rely on H2-O for T-cell activation indicating DM-resistance. By introducing mutations within the T-cell epitopes we could generate one further DM-sensitive variant of OVA and two DM-resistant counterparts. Likewise, we designed DM-resistant and DM-sensitive variants of DBY. On vaccination of C57BL/6 mice with either epitope variant we measured comparable expansion and reactivity of OVA-specific and DBY-specific T-cells both in vivo and ex vivo. By generating T-cell lines and clones of healthy human donors we showed that DM-sensitive antigens are targeted by the natural T-cell repertoire. Conclusion We successfully generated DM-sensitive and DM-resistant variants for two model antigens. Thereby, we demonstrated that DM-sensitive antigens are not inferior to their DM-resistant counterpart and are therefore interesting tools for immunotherapy after allogeneic stem cell transplantation.
Abstract 11457: Junctional Rhythm Following Transcatheter Aortic Valve Replacement
Authors: Natthapon Angsubhakorn, Baris Akdemir, Stefan C Bertog, Santiago Garcia, Wasawat Vutthikraivit, Selcuk Adabag
Journal: Circulation (2019)

Introduction: Cardiac conduction system abnormalities are common after transcatheter aortic valve replacement (TAVR). However, little is known about the implications of accelerated junctional rhyth...
Squalene epoxidase promotes colorectal cancer cell proliferation through accumulating calcitriol and activating CYP24A1‐mediated MAPK signaling
Authors: Luwei He, Huaguang Li, Chenyu Pan, Yutong Hua, Jiayin Peng, Zhaocai Zhou, Yun Zhao, Moubin Lin
Journal: Cancer Communications (2021)

Abstract Background Colorectal cancer (CRC) is one of the most malignant tumors with high incidence, yet its molecular mechanism is not fully understood, hindering the development of targeted therapy. Metabolic abnormalities are a hallmark of cancer. Targeting dysregulated metabolic features has become an important direction for modern anticancer therapy. In this study, we aimed to identify a new metabolic enzyme that promotes proliferation of CRC and to examine the related molecular mechanisms. Methods We performed RNA sequencing and tissue microarray analyses of human CRC samples to identify new genes involved in CRC. Squalene epoxidase ( SQLE ) was identified to be highly upregulated in CRC patients. The regulatory function of SQLE in CRC progression and the therapeutic effect of SQLE inhibitors were determined by measuring CRC cell viability, colony and organoid formation, intracellular cholesterol concentration and xenograft tumor growth. The molecular mechanism of SQLE function was explored by combining transcriptome and untargeted metabolomics analysis. Western blotting and real‐time PCR were used to assess MAPK signaling activation by SQLE. Results SQLE‐related control of cholesterol biosynthesis was highly upregulated in CRC patients and associated with poor prognosis. SQLE promoted CRC growth in vitro and in vivo . Inhibition of SQLE reduced the levels of calcitriol (active form of vitamin D3) and CYP24A1, followed by an increase in intracellular Ca 2+ concentration. Subsequently, MAPK signaling was suppressed, resulting in the inhibition of CRC cell growth. Consistently, terbinafine, an SQLE inhibitor, suppressed CRC cell proliferation and organoid and xenograft tumor growth. Conclusions Our findings demonstrate that SQLE promotes CRC through the accumulation of calcitriol and stimulation of CYP24A1‐mediated MAPK signaling, highlighting SQLE as a potential therapeutic target for CRC treatment.
乳癌におけるFGFR-2,STAT5,およびプロゲステロン受容体の相互作用
Authors: P Cerliani Juan, Guillardoy Tomas, Giulianelli Sebastian, P Vaque Jose, Gutkind J. Silvio, I Vanzulli Silvia, Martins Ruben, Zeitlin Eduardo, A Lamb Caroline, Lanari Claudia
Journal: Cancer Research (2011)
Abstract 15662: Type IV Collagen 7S And Hyaluronic Acid Predict The Early Stage Of Liver Cirrhosis In Patients After Fontan Procedure
Authors: Kazuyoshi Saito, Sayaka Ozawa, Ayano Inui, Tomoh Fujisawa, Kazuhiro Watanabe, Fukiko Ichida, Naoki Yoshimura, Toshio Miyawaki
Journal: Circulation (2011)

Introduction: The aim of this study was to identify useful biochemical fibrosis markers for the early detection of developing liver fibrosis or liver cirrhosis in patients after Fontan operation. M...
In patients having transjugular intrahepatic portosystemic shunt, rifaximin prevented overt hepatic encephalopathy
Authors: Ronald L. Koretz
Journal: Annals of Internal Medicine (2021)

Source Citation Bureau C, Thabut D, Jezequel C, et al. The use of rifaximin in the prevention of overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: a randomized controlled trial. Ann Intern Med. 2021;174:633-40. 33524293
Host-emitted amino acid cues regulate bacterial chemokinesis to enhance colonization
Authors: Catherine D. Robinson, Emily G. Sweeney, Julia Ngo, Emily Ma, Arden Perkins, T. Jarrod Smith, Nicolas L. Fernandez, Christopher M. Waters, S. James Remington, Brendan J.M. Bohannan, Karen Guillemin
Journal: Cell Host & Microbe (2021)
Abstract 2958: Drug induced resistant tumor models enable the development of next-generation anticancer therapeutics
Authors: Ting Ni, Zhixiang Zhang, Xuzhen Tang, Wenting Shi, Qingyang Gu, Qunsheng Ji
Journal: Cancer Research (2021)

Abstract Recent advances in cancer biology and diagnosis are providing more targeted approaches to treat cancers. Therapy targeting the specific oncogenic driver could inhibit tumor progression and helps to a favorable prognosis in clinical practice. Recently, the discovery of driver mutations in various cancers such as EGFR, ER, CDK, c–MET, TRK and BTK provides a personalized targeted treatment. However, most patients who initially benefit a lot from targeted therapies eventually become resistant to treatments. Acquired resistance limits the long–term efficacy. The commonly acquired resistant mechanisms include target gene mutation, alternative pathway activation, histological or phenotypic transformation and so on. Although a variety of mechanisms of acquired resistance have been reported, optimal treatment for acquired resistance is not yet clearly defined. To mimic the clinical resistant after long–term treatment, we established a panel of in vivo induced drug resistant CDX and PDX models by continuous dosing of targeted drugs to mice, covering a series of first–line targeted drugs Tamoxifen, Olaparib, BMN–673, Ibrutinib, Crizotinib, Erlotinib, Palbociclib, Capmatinib, Entrectinib, Cabozantinib, Sorafenib and Irinotecan. Resistant models were derived from sensitive models harboring specific oncogenic driver. Regrowth tumors were continually treated with targeted drugs and passaged several times until a stable drug resistance phenotype occurred. To explore the resistant mechanisms, we performed WES and RNA–seq analysis in the gene expression levels, and western blotting and IHC staining in the protein expression levels. In summary, these drug induced resistant tumor models provide an opportunity to evaluate the next–generation anticancer therapeutics to overcome therapeutic resistance in tumors. Citation Format: Ting Ni, Zhixiang Zhang, Xuzhen Tang, Wenting Shi, Qingyang Gu, Qunsheng Ji. Drug induced resistant tumor models enable the development of next-generation anticancer therapeutics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2958.
Abstract 1708: Improving genotype specific chemotherapy response in ovarian cancer via cGAS-STING pathway activation
Authors: Noor Shakfa, Elizabeth Lightbody, Deyang Li, Juliette Wilson-Sanchez, Gwenaelle Conseil, Afrakoma Afriyie-Asante, Stephen Chenard, Ali Hamade, Madhuri Koti
Journal: Cancer Research (2021)

Abstract High grade serous ovarian carcinoma (HGSC) is the most lethal gynecologic malignancy with high rates of chemotherapy resistance and poor outcomes. Our previous studies have demonstrated the variable tumor immune microenvironment states that associate with platinum chemotherapy response. We further showed the significance of the interferon (IFN) induced chemokine CXCL10 as a key mediator of tumor infiltrating immune cell recruitment. Using the ID8-Trp53−/− murine model of HGSC, we demonstrated the potential of Stimulator of Interferon Genes (STING) pathway activation in enhancing response of HGSC tumors to carboplatin chemotherapy and sensitizing them to immune checkpoint blockade therapy through a heightened type 1 IFN (IFN1) response. CXCL10 production via IFN1 is also governed by genes that regulate cellular DNA damage repair pathways. Evolving evidence indicates a role of BRCA1 and PTEN genes in mediating cellular IFN1 responses. Losses in the function of these genes is widely prevalent in a large proportion of HGSC tumors, where tumors with BRCA1 mutations (~25% of HGSC cases) have higher CD8+ T cell infiltration in contrast to those with loss of PTEN (~10% of cases). We hypothesized that HGSC tumors with loss of PTEN expression can be rendered susceptible to immune mediated killing via activating the STING pathway. Tumors generated from ID8-Trp53−/−; Brca1−/− cells and those from ID8-Trp53−/−; Pten−/− cells in C57BL6 mice showed significant immunologic differences through local and systemic immune profiling. The addition of STING agonist treatment significantly increased chemosensitivity and improved overall response in mice implanted with ID8-Trp53−/−; Pten−/− cells compared to those treated with carboplatin alone, altering immune responses. This study is foundational to inform rational combinations of STING pathway activating therapies in HGSC, augmenting responses to existing chemotherapy regimens and prolonging survival rates in patients. Citation Format: Noor Shakfa, Elizabeth Lightbody, Deyang Li, Juliette Wilson-Sanchez, Gwenaelle Conseil, Afrakoma Afriyie-Asante, Stephen Chenard, Ali Hamade, Madhuri Koti. Improving genotype specific chemotherapy response in ovarian cancer via cGAS-STING pathway activation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1708.
Single-Cell Analyses Reveal Diverse Mechanisms of Resistance to EGFR Tyrosine Kinase Inhibitors in Lung Cancer
Authors: Yukie Kashima, Daisuke Shibahara, Ayako Suzuki, Kyoko Muto, Ikei S. Kobayashi, David Plotnick, Hibiki Udagawa, Hiroki Izumi, Yuji Shibata, Kosuke Tanaka, Masanori Fujii, Akihiro Ohashi, Masahide Seki, Koichi Goto, Katsuya Tsuchihara, Yutaka Suzuki, Susumu S. Kobayashi
Journal: Cancer Research (2021)

Tumor heterogeneity underlies resistance to tyrosine kinase inhibitors (TKI) in lung cancers harboring EGFR mutations. Previous evidence suggested that subsets of preexisting resistant cells are selected by EGFR-TKI treatment, or alternatively, that diverse acquired resistance mechanisms emerge from drug-tolerant persister (DTP) cells. Many studies have used bulk tumor specimens or subcloned resistant cell lines to identify resistance mechanism. However, intratumoral heterogeneity can result in divergent responses to therapies, requiring additional approaches to reveal the complete spectrum of resistance mechanisms. Using EGFR-TKI-resistant cell models and clinical specimens, we performed single-cell RNA-seq and single-cell ATAC-seq analyses to define the transcriptional and epigenetic landscape of parental cells, DTPs, and tumor cells in a fully resistant state. In addition to AURKA, VIM, and AXL, which are all known to induce EGFR-TKI resistance, CD74 was identified as a novel gene that plays a critical role in the drug-tolerant state. In vitro and in vivo experiments demonstrated that CD74 upregulation confers resistance to the EGFR-TKI osimertinib and blocks apoptosis, enabling tumor regrowth. Overall, this study provides new insight into the mechanisms underlying resistance to EGFR-TKIs. SIGNIFICANCE: Single-cell analyses identify diverse mechanisms of resistance as well as the state of tolerant cells that give rise to resistance to EGFR tyrosine kinase inhibitors.
Influence of the COVID-19 outbreak on urgent and elective surgical management of urolithiasis: A global perspective
Authors: A. Artiles Medina, I. Laso García, M. Mata Alcaraz, S. Arribas Terradillos, M. Hevia Palacios, G. Duque Ruiz, F. Arias Funez, F.J. Burgos Revilla
Journal: European Urology (2021)