tbuckley/cabot-search huggingface dataset:
ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease
Authors: N. Colombo, C. Sessa, A. du Bois, J. Ledermann, W.G. McCluggage, I. McNeish, P. Morice, S. Pignata, I. Ray-Coquard, I. Vergote, T. Baert, I. Belaroussi, A. Dashora, S. Olbrecht, F. Planchamp, D. Querleu, T. Baert, S. Banerjee, I. Belaroussi, P. Blecharz, I. Bruchim, D. Cibula, N. Colombo, N. Concin, B. Davidson, A. Dashora, M. Devouassoux-Shisheboran, A. du Bois, A. Ferrero, R. Glasspool, A. González-Martin, V. Heinzelmann-Schwarz, F. Joly, J.W. Kim, F. Kridelka, J. Ledermann, D. Lorusso, S. Mahner, W.G. McCluggage, I. McNeish, M. Mikami, M.R. Mirza, P. Morice, S. Nicum, S. Olbrecht, D.M. O’Donnell, P. Pautier, F. Planchamp, S. Pignata, D. Querleu, I. Ray-Coquard, A. Rodolakis, J. Sehouli, F. Selcukbiricik, C. Sessa, N. Singh, D.S.P. Tan, D. Timmerman, G. Tognon, J. van der Velden, I. Vergote, P.O. Witteveen, A.G. Zeimet
Journal: Annals of Oncology (2019)
Abstract 10077: Decisions Informed by Computing Entities (DICE) to Improve Prognostic Value of Myocardial Perfusion Imaging: The NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study
Authors: Mark Doyle, Gerald M Pohost, Leslee J Shaw, DianeMS A Vido, Sheryl F Kelsey, Delia B Johnson, William J Rogers, Geetha Rayarao, Barry L Sharaf, Carl J Pepine, Noel B Merz, Robert W Biederman
Journal: Circulation (2011)

Introduction:  Quantitative analysis can improve myocardial perfusion imaging (MPI) for prediction of prognosis. We have designed a novel approach, Decisions Informed by Computed Entities (DICE), to enhance the prognostic ability of MPI data to predict major adverse cardiovascular events (MACE) in women with suspected ischemic heart disease. We applied DICE to cardiovascular magnetic resonance imaging (CMRI) and Single Positron Computed Tomography (SPECT) MPI data sets in the Women9s Ischemia Syndrome Evaluation (WISE) Study.   Methods:  Women (n=228), mean age 59±11yrs, with symptoms suggestive of myocardial ischemia underwent MPI and cardiac function evaluation separately by CMRI and SPECT and were followed (40±17mo) for time to MACE (CV death, MI, and hospitalization for CHF). Abnormal perfusion defects were noted for each MPI modality (clinical reading). Cardiac regions were separately evaluated and at least one abnormal region was considered a positive study. The CMRI data were evaluated using qualitative (QLMR) and semi-quantitative (SQMR) approaches. Multiple linear regression models (DICE models) were generated, each predicting MPI status from one modality (e.g. CMRI) using data from a second modality (e.g. SPECT). Two DICE models were constructed from pairs of data sets and included variables such as end-systolic volume and myocardial wall thickness in addition to the clinical MPI reading.   Results:  MACE occurred in 29 women (13%). The percentage of MACE occurring in pts with abnormal perfusion was 43% using the average of the clinical MPI readings vs. 75% for the average of the DICE models (p   Conclusions:  DICE modeling, incorporating the clinical MPI reading and cardiac variables derived from one imaging modality predicted the clinical MPI reading of a second modality while increasing the prognostic value as compared to just the clinical reading. The predictive power of the DICE model increases with the number of variables measured while simultaneously reducing noise and bias.
Abstract PR05: Elucidating role of bacteria during pancreatic ductal adenocarcinoma (PDAC)
Authors: Vidhi Chandra, Olivereen Le Roux, Erick Riquelme, Yu Zhang, Anirban Maitra, James. R White, Florencia McAllister
Journal: Cancer Research (2020)

Abstract Long-term survival in pancreatic cancer (PC) is rare as only a minority of all resected patients survive for &amp;gt;5 years. Interestingly, somatic mutations do not predict long-term survivorship, highlighting the potential role of extrinsic factors. Recent studies have reported the role of the gut and tumor microbiome in pancreatic tumorigenesis and PC treatment responses. Since intratumoral bacteria have been detected in human PC tumors, possibly arising from relocation of intestinal bacteria, it is possible that intratumoral T cells get primed with microbial antigens within the tumor microenvironment. To reconstruct bacterial phylogenies, we performed prokaryotic 16S ribosomal RNA sequencing and immunoprofiling of PC tumors from “Long-Term Survivors-LTS” (&amp;gt;5y post-resection) and “Short-Term Survivors-STS” (&amp;lt;5y post-resection). Strikingly, we found that LTS from both discovery and validation cohorts had higher microbial diversity and LTS from both cohorts were enriched for a tumor microbial signature: Pseudoxanthomonas, Streptomyces, Saccharopolyspora, and Bacillus clausii. Moreover, the most overrepresented species in LTS tumors strongly correlated with enhanced immunoactivation of the tumor microenvironment, suggestive of bacterial-mediated immune cell recruitment and activation. Based on these findings, we hypothesized that gut bacteria affect PC by triggering immune responses either locally by migrating to the tumor or systemically through responses originating in the gut. To test this, we performed in vitro studies and found that single bacterial species identified from LTS tumor microbial signature can induce activation of cytotoxic T lymphocytes (CD8+ CD69+ IFNg+) only when in direct contact with antigen-presenting cells, suggesting that bacterial antigens need to be processed and presented to intratumoral T cells to induce their activation. Furthermore, through preliminary in vivo studies, we have found that orally administered single bacterial species can be delivered to the pancreas via the gut. Further work needs to determine whether single/specific LTS bacteria play a causative role in regulating tumor immunity in vivo. If the beneficial modulatory role of specific bacteria is established, then bacteriotherapy as single therapy or in combination with fecal microbial transplants could be used as innovative strategies for treatment of pancreatic cancer. This abstract is also being presented as Poster B27. Citation Format: Vidhi Chandra, Olivereen Le Roux, Erick Riquelme, Yu Zhang, Anirban Maitra, James. R White, Florencia McAllister. Elucidating role of bacteria during pancreatic ductal adenocarcinoma (PDAC) [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr PR05.
Abstract 18000: Elevated Plasma Soluble Urokinase Plasminogen Activator Receptor (suPAR) Levels are Associated With Impaired Myocardial Strain as Assessed by Speckle Tracking Echocardiography in Patients With Stage IV Non-Small Cell Lung Cancer
Authors: Ahmad S Manshad, Fatima A Ballout, Jeffrey A Borgia, Jochen Reiser, Tochukwu M Okwuosa
Journal: Circulation (2017)

Introduction: Cardiac toxicity is a common and often fatal complication of cancer therapy, and early detection of patients at risk for cardiac dysfunction allows for timely intervention. Soluble ur...
Impact of a preceding radiotherapy on the outcome of immune checkpoint inhibition in metastatic melanoma: a multicenter retrospective cohort study of the DeCOG
Authors: Sarah Knispel, Andreas Stang, Lisa Zimmer, Hildegard Lax, Ralf Gutzmer, Lucie Heinzerling, Carsten Weishaupt, Claudia Pföhler, Anja Gesierich, Rudolf Herbst, Katharina C Kaehler, Benjamin Weide, Carola Berking, Carmen Loquai, Jochen Utikal, Patrick Terheyden, Martin Kaatz, Max Schlaak, Alexander Kreuter, Jens Ulrich, Peter Mohr, Edgar Dippel, Elisabeth Livingstone, Jürgen C Becker, Michael Weichenthal, Eleftheria Chorti, Janine Gronewold, Dirk Schadendorf, Selma Ugurel
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Immune checkpoint inhibition (ICI) is an essential treatment option in melanoma. Its outcome may be improved by a preceding radiation of metastases. This study aimed to investigate the impact of a preceding radiotherapy on the clinical outcome of ICI treatment. Methods This multicenter retrospective cohort study included patients who received anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) or anti-programmed cell death protein 1 (PD-1) ICI with or without preceding radiotherapy for unresectable metastatic melanoma. ICI therapy outcome was measured as best overall response (BOR), progression-free (PFS) and overall survival (OS). Response and survival analyses were adjusted for confounders identified by directed acyclic graphs. Adjusted survival curves were calculated using inverse probability treatment weighting. Results 835 patients who received ICI (anti-CTLA-4, n=596; anti-PD-1, n=239) at 16 centers were analyzed, whereof 235 received a preceding radiotherapy of metastatic lesions in stage IV disease. The most frequent organ sites irradiated prior to ICI therapy were brain (51.1%), lymph nodes (17.9%) and bone (17.9%). After multivariable adjustment for confounders, no relevant differences in ICI therapy outcome were observed between cohorts with and without preceding radiotherapy. BOR was 8.7% vs 13.0% for anti-CTLA-4 (adjusted relative risk (RR)=1.47; 95% CI=0.81 to 2.65; p=0.20), and 16.5% vs 25.3% for anti-PD-1 (RR=0.93; 95% CI=0.49 to 1.77; p=0.82). Survival probabilities were similar for cohorts with and without preceding radiotherapy, for anti-CTLA-4 (PFS, adjusted HR=1.02, 95% CI=0.86 to 1.25, p=0.74; OS, HR=1.08, 95% CI=0.81 to 1.44, p=0.61) and for anti-PD-1 (PFS, HR=0.84, 95% CI=0.57 to 1.26, p=0.41; OS, HR=0.73, 95% CI=0.43 to 1.25, p=0.26). Patients who received radiation last before ICI (n=137) revealed no better survival than those who had one or more treatment lines between radiation and start of ICI (n=86). In 223 patients with brain metastases, we found no relevant survival differences on ICI with and without preceding radiotherapy. Conclusions This study detected no evidence for a relevant favorable impact of a preceding radiotherapy on anti-CTLA-4 or anti-PD-1 ICI treatment outcome in metastatic melanoma.
HER2 antibody-drug conjugate controls growth of breast cancer brain metastases in hematogenous xenograft models, with heterogeneous blood–tumor barrier penetration unlinked to a passive marker
Authors: Brunilde Gril, Debbie Wei, Alexandra S Zimmer, Christina Robinson, Imran Khan, Simone Difilippantonio, Michael G Overstreet, Patricia S Steeg
Journal: Neuro-Oncology (2020)

Abstract Background Brain metastases of HER2+ breast cancer persist as a clinical challenge. Many therapeutics directed at human epidermal growth factor receptor 2 (HER2) are antibodies or antibody-drug conjugates (ADCs), and their permeability through the blood–tumor barrier (BTB) is poorly understood. We investigated the efficacy of a biparatopic anti-HER2 antibody-tubulysin conjugate (bHER2-ATC) in preclinical models of brain metastases. Methods The compound was evaluated in 2 hematogenous HER2+ brain metastasis mouse models, SUM190-BR and JIMT-1-BR. Endpoints included metastasis count, compound brain penetration, cancer cell proliferation, and apoptosis. Results Biparatopic HER2-ATC 3 mg/kg prevented metastasis outgrowth in the JIMT-1-BR model. At 1 mg/kg bHER2-ATC, a 70% and 92% reduction in large and micrometastases was observed. For the SUM190-BR model, an 85% and 53% reduction, respectively, in large and micrometastases was observed at 3 mg/kg, without statistical significance. Proliferation was reduced in both models at the highest dose. At the endpoint, bHER2-ATC uptake covered a median of 4–6% and 7–17% of metastasis area in the JIMT-1-BR and SUM190-BR models, respectively. Maximal compound uptake in the models was 19% and 86% in JIMT-1-BR and SUM190-BR, respectively. Multiple lesions in both models demonstrated ADC uptake in the absence or low diffusion of Texas Red Dextran, a marker of paracellular permeability. Using in vitro BTB assays, the ADC was endocytosed into brain endothelial cells, identifying a potentially new mechanism of antibody permeability. Conclusions Biparatopic HER2-ATC significantly prevented JIMT-1-BR brain metastasis outgrowth and showed activity in the SUM190-BR model. The bHER2-ATC penetration into metastases that are impermeable to fluorescent dye suggested an endocytic mechanism of brain penetration.
Abstract 15088: RNA-Seq Reveals New Insights Into the Protective Role of ANGPTL4 Against Mouse Myocardial Ischemia/ Reperfusion Injury
Authors: Dilyara Cheranova, S. Q. Ye
Journal: Circulation (2013)

Introduction: Angiopoietin-like protein 4 (ANGPTL4) is a dual-function protein: an inhibitor of lipoprotein and hepatic lipases with angiogenic properties. Its E40K mutation is associated with an i...
Long-term effectiveness and safety of secukinumab for treatment of refractory mucosal and articular Behçet’s phenotype: a multicentre study
Authors: Filippo Fagni, Alessandra Bettiol, Rosaria Talarico, Giuseppe Lopalco, Elena Silvestri, Maria Letizia Urban, Paul A J Russo, Gerardo Di Scala, Giacomo Emmi, Domenico Prisco
Journal: Annals of the Rheumatic Diseases (2020)

To evaluate the effectiveness and safety of secukinumab in patients with a mucosal and articular Behçet's phenotype resistant to conventional and biologic treatment.A multicentre retrospective study was performed on 15 patients with a mucosal and articular phenotype of Behçet's syndrome fulfilling the International Criteria for Behçet's Disease and refractory to treatment with colchicine, disease-modifying antirheumatic drugs and at least one antitumour necrosis factor-α agent. Minimum follow-up was set at 6 months. Six patients with a polyarticular involvement were treated with secukinumab 300 mg/month, while all other cases received secukinumab 150 mg/month. Dose increase from 150 to 300 mg per month and shortening of administration frequency were allowed for poor disease control. Response evaluation was based on the number of oral ulcers in the previous 28 days and Disease Activity Score-28 for articular manifestations.At 3 months of follow-up, nine (66.7%) patients achieved a response (complete or partial), and this proportion further increased to 86.7% at 6 months, 76.9% at 12 months, 90.0% at 18 months and 100.0% after 24 months. Notably, all patients who started with secukinumab 300 mg/month achieved complete response by month 6. Seven (46.7%) patients could achieve a response only after switching to a higher dosage.Our study suggests that secukinumab at a dose of 150 and 300 mg per month is safe and effective for the long-term treatment of patients with Behçet's syndrome with a mucosal and articular phenotype refractory to previous treatments. Notably, secukinumab 300 mg/month resulted in superior complete mucosal and articular responses with no serious or dose-related adverse effects.
Two-photon probes for pH: Detection of human colon cancer using two-photon microscopy.
Authors: Woojung Kim, Eun Sun Kim, Geeho Min, Seung Han Kim, Seong ji Choi, Jung Min Lee, Jae Min Lee, Hyuk Soon Choi, Bora Keum, Yoon Tae Jeen, Hong Sik Lee, Hoon Jai Chun, Chang Duck Kim, Seung Taek Hong, Jung-Nyoung Heo, Bong Rae Cho
Journal: Journal of Clinical Oncology (2018)

607 Background: In cancer cells, lysosomal pH decreases along with a concomitant increase in lysosomal volume and cathepsin expression levels. Lysosomes also play crucial roles in cancer progression following their release into the extracellular space. Since cancer cells invade a tissue by secreting degradative enzymes, the extracellular pH of tumor tissues becomes acidic. However, to date, there has been no report on the use of multi-photon microscopy (MPM) probes to image human colon cancer tissues. Methods: We have developed multi-photon (MP) pH-sensitive probes (BH-2 and BHEt-1) that exhibit absorption and emission maxima at 370 and 466 nm, and TP absorption cross-section values of 51 and 61 GM (1 GM = 10−50 cm4 s/photon), respectively, at 750 nm and pH 3.0 in a universal buffer (0.1 M citric acid, 0.1 M KH2PO4, 0.1 M Na2B4O7, 0.1 M Tris, 0.1 M KCl)/1,4-dioxane (7/ 3) solution. Results: The TPM images of CCD-18co (a normal colon cell line) and HCT116 cells (a colon cancer cell line) labeled with BH-2 were too dim to be distinguished. When the same cells were labeled with BHEt-1, however, the MPM image of the HCT116 cells was much brighter than that of CCD-18co cells, and the relative proportion of the acidic vesicles (Pacid) of the former was 5-fold larger than that of latter. BHEt-1 could also differentiate HepG2 cells (a human liver cancer cell line) from LX-2 cells (a human hepatic stellate cell line) with a 6-fold larger P acid value. Human colon cancer tissues labeled with BHEt-1 showed similar results, demonstrating much brighter MPM images and 6-fold larger Pacid values compared to normal tissue. Conclusions: These results suggest the potential utility of BHEt-1 for molecular image analysis of colon cancer tissues using MPM.
Abstract 17020: Visit-to-visit Variability of Systolic Blood Pressure Predicts All-cause Mortality in Patients Received Percutaneous Coronary Intervention With Drug Eluting Stents
Authors: Suk Min Seo, Ik Jun Choi, Doo Soo Jeon, Jin Jin Kin
Journal: Circulation (2015)

Background: Blood pressure (BP) and its variability are associated with atherosclerotic disease and cardiovascular events. The prognostic implications of outpatient clinic visit-to-visit blood pressure variability (BPV) are unknown in patients received percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Methods: Patients who PCI from January 2009 to December 2013 were consecutively corrected. We analyzed the 1,234 patients, who measured clinic BP more than three times during follow up. The BPV is determined by standard deviation (SD) of systolic and diastolic BP, and coefficient of variation (SD*100/mean BP). Results: Median follow up duration was 905 days (interquartile range 529 to 1,310 days). The clinic measured BP were recorded mean 9.9 ± 4.7 times. All patients were divided into two groups according to the coefficient of variation of systolic BP (CVSBP); high CVSBP group (&gt; 8.77, n=617) and low CVSBP group (&lt;8.77, n=617). High CVSBP group had significantly higher all-cause mortality (7.9 versus 3.1%, p&lt;0.001). In multivariate logistic regression analysis for prediction of all-cause mortality after PCI with DES, hazard ratio of high CVSBP group was 2.090 (95% of confidence interval 1.012-4.318, p = 0.046). Conclusion: The higher visit-to-visit BPV is associated higher mortality in patients performed PCI with DES. The clinic measured visit-to-visit BPV may serve as a predictor of mortality after PCI with DES.
Leishmaniavirus genetic diversity is not related to leishmaniasis treatment failure
Authors: M. Ginouvès, P. Couppié, S. Simon, E. Bourreau, S. Rogier, P. Brousse, P. Travers, V. Pommier de Santi, M. Demar, S. Briolant, G. Prévot
Journal: Clinical Microbiology and Infection (2020)
European Association of Urology Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2020 Guidelines
Authors: J. Alfred Witjes, Harman Max Bruins, Richard Cathomas, Eva M. Compérat, Nigel C. Cowan, Georgios Gakis, Virginia Hernández, Estefania Linares Espinós, Anja Lorch, Yann Neuzillet, Mathieu Rouanne, George N. Thalmann, Erik Veskimäe, Maria J. Ribal, Antoine G. van der Heijden
Journal: European Urology (2020)
Mortality and Paclitaxel-Coated Devices
Authors: Krishna J. Rocha-Singh, Sue Duval, Michael R. Jaff, Peter A. Schneider, Gary M. Ansel, Sean P. Lyden, Christopher M. Mullin, John P.A. Ioannidis, Sanjay Misra, Abraham R. Tzafriri, Elazer R. Edelman, Juan F. Granada, Christopher J. White, Joshua A. Beckman
Journal: Circulation (2020)

Paclitaxel-containing devices (PTXDs) significantly reduce reintervention in patients with symptomatic femoropopliteal peripheral artery disease. A recent aggregate-data meta-analysis reported increased late mortality in patients with peripheral artery disease treated with PTXDs. We performed an individual patient data meta-analysis to evaluate mortality.Manufacturers of US Food and Drug Administration-approved and commercially available devices in the United States provided deidentified individual patient data for independent analysis. Cox proportional hazards 1-stage meta-analysis models using intention-to-treat methods were used for the primary analysis. A secondary analysis of recovered missing vital status data was performed. The impact of control crossover to PTXDs, cause-specific mortality, and drug dose mortality were assessed.A total of 2185 subjects and 386 deaths from 8 PTXD trials with 4-year median follow-up were identified. The primary analysis indicated a 38% (95% CI, 6% to 80%) increased relative mortality risk, corresponding to 4.6% absolute increase, at 5 years associated with PTXD use. Control and treatment arm loss to follow-up and withdrawal were 24% and 23%, respectively. With inclusion of recovered vital status data, the excess relative mortality risk was 27% (95% CI, 3%-58%). This observation was consistent across various scenarios, including as-treated analyses, with no evidence of increased risk over time with PTXDs. Mortality risk tended to be increased for all major causes of death. There were no subgroup differences. No drug dose-mortality association was identified.This individual patient data meta-analysis, based on the most complete available data set of mortality events from PTXD randomized controlled trials, identified an absolute 4.6% increased mortality risk associated with PTXD use.
SAT0530 SPSAMRIS: A TIME AND RESOURCE SAVING ALTERNATIVE FOR DETECTION AND MONITORING OF DISEASE-RELATED JOINT CHANGES?
Authors: Philipp Sewerin, Daniel Abrar, Ralph Brinks, Stefan Vordenbäumen, Alexander Lautwein, Matthias Schneider, Benedikt Ostendorf, Christoph Schleich
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Standardized imaging scores in MRI are barley used in daily clinical practice whereby the high expenditure (in terms of time and staff) is often given as a reason. <h3>Objectives:</h3> To develop and evaluate a simplified version of the OMERACT Psoriatic Arthritis Magnetic Resonance Imaging Score (PsAMRIS). <h3>Methods:</h3> 19 patients with PsA according to CASPAR classification criteria with inadequate methotrexate response received anti-TNF treatment and were assessed by 3T MRI of the clinically dominant hand at baseline and after 6 months. Scoring was according to PsAMRIS. Items were reduced based on standard response mean (SRM) resulting in sPsAMRIS, which was compared to PsAMRIS by calculation of the total SRM and relative efficiency (RE) after bootstrapping. <h3>Results:</h3> PsAMRIS subscore of MCP3, 4, and PIP4 resulted in the highest SRM (-0.07 each) and were therefore included in sPsAMRIS. sPsAMRIS had higher SRM compared to PsAMRIS (-0.13 vs. -0.02) and a higher RE (29.46). PsAMRIS and sPsAMRIS highly correlated at baseline (r= 0.75; p &lt; 0.01) and follow-up (r= 0.64; p= 0.01). Evaluation time was reduced from 471 to 142 seconds at baseline and from 478 to 133 seconds at follow-up (p &lt; 0.001). <h3>Conclusion:</h3> The abbreviated MRI scoring system for PsA-related changes in hands, sPsAMRIS, showed a strong correlation with the well-evaluated PsAMRIS. Hence, sPsAMRIS can be considered as a time and resource saving alternative for semi-quantitative evaluation and monitoring of PsA related joint-pathology. <h3>Acknowledgement:</h3> The project was funded by a grant from the German "Bundesministerium für Bildung und Forschung"(BMBF), ArthroMark (01EC1009). <h3>Disclosure of Interests:</h3> Philipp Sewerin: None declared, Daniel Abrar: None declared, Ralph Brinks: None declared, Stefan Vordenbäumen: None declared, Alexander Lautwein: None declared, Matthias Schneider Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study., Speakers bureau: Chugai, Benedikt Ostendorf: None declared, Christoph Schleich: None declared