tbuckley/cabot-search huggingface dataset:
Epsins 1 and 2 promote NEMO linear ubiquitination via LUBAC to drive breast cancer development
Authors: Kai Song, Xiaofeng Cai, Yunzhou Dong, Hao Wu, Yong Wei, Uma T. Shankavaram, Kui Cui, Yang Lee, Bo Zhu, Sudarshan Bhattacharjee, Beibei Wang, Kun Zhang, Aiyun Wen, Scott Wong, Lili Yu, Lijun Xia, Alana L. Welm, Diane R. Bielenberg, Kevin A. Camphausen, Yibin Kang, Hong Chen
Journal: Journal of Clinical Investigation (2020)

Estrogen receptor-negative (ER-negative) breast cancer is thought to be more malignant and devastating than ER-positive breast cancer. ER-negative breast cancer exhibits elevated NF-κB activity, but how this abnormally high NF-κB activity is maintained is poorly understood. The importance of linear ubiquitination, which is generated by the linear ubiquitin chain assembly complex (LUBAC), is increasingly appreciated in NF-κB signaling, which regulates cell activation and death. Here, we showed that epsin proteins, a family of ubiquitin-binding endocytic adaptors, interacted with LUBAC via its ubiquitin-interacting motif and bound LUBAC's bona fide substrate NEMO via its N-terminal homolog (ENTH) domain. Furthermore, epsins promoted NF-κB essential modulator (NEMO) linear ubiquitination and served as scaffolds for recruiting other components of the IκB kinase (IKK) complex, resulting in the heightened IKK activation and sustained NF-κB signaling essential for the development of ER-negative breast cancer. Heightened epsin levels in ER-negative human breast cancer are associated with poor relapse-free survival. We showed that transgenic and pharmacological approaches eliminating epsins potently impeded breast cancer development in both spontaneous and patient-derived xenograft breast cancer mouse models. Our findings established the pivotal role epsins played in promoting breast cancer. Thus, targeting epsins may represent a strategy to restrain NF-κB signaling and provide an important perspective into ER-negative breast cancer treatment.
293P Impact of tucatinib on progression free survival in patients with HER2+ metastatic breast cancer and stable or active brain metastases
Authors: T. Bachelot, N.U. Lin, R.K. Murthy, S.A. Hurvitz, V. Borges, M. Oliveira, C. Oakman, S. Khan, C. Lynch, K. Westbrook, C. Doyle, M. Reinisch, M.A. Colleoni, D. Slamon, G.N. Hortobagyi, E.P. Winer, S. McGoldrick, X. An, S. Loibl
Journal: Annals of Oncology (2020)
COVID-19 Severity and Outcomes in Patients With Cancer: A Matched Cohort Study
Authors: Gagandeep Brar, Laura C. Pinheiro, Michael Shusterman, Brandon Swed, Evgeniya Reshetnyak, Orysya Soroka, Frank Chen, Samuel Yamshon, John Vaughn, Peter Martin, Doru Paul, Manuel Hidalgo, Manish A. Shah
Journal: Journal of Clinical Oncology (2020)

SARS-CoV-2 (COVID-19) is a systemic infection. Patients with cancer are immunocompromised and may be vulnerable to COVID-related morbidity and mortality. The objectives of this study were to determine if patients with cancer have worse outcomes compared with patients without cancer and to identify demographic and clinical predictors of morbidity and mortality among patients with cancer.
513P Prospective evaluation of the G8 screening tool for predicting survival in elderly patients with colon cancer
Authors: G. Soler, R. Legido, X. Perez, M. Martinez-Villacampa, C. Santos, F. Losa, J.C. Ruffinelli, N. Mulet, A. Teule, R. Castany, R. Gallego, M. Carbonell, A. Manzana, A. Rios, J. Saldaña, R. Salazar
Journal: Annals of Oncology (2020)
411P A randomized, open-label, parallel-design phase III study to compare adjuvant 5-FU plus oxaliplatin (mFLOX) versus observation in locally advanced rectal cancer after neoadjuvant chemoradiation
Authors: M.I. Braghiroli, C.M.V. Moniz, R.S.P. Riechelmann, A.F.L. Dornellas, F. Caparelli, L. Alban, A. Alex, G.M. Bariani, L.A. Senna Leite, T. Giollo Rivelli, D. Nebuloni, C. Ortega, O.F.M. Braghiroli, K. Moutinho, S. Nahas, C. Nahas, G. Cotti, J. Sabbaga, I. Ceconello, P.M. Hoff
Journal: Annals of Oncology (2020)
747P Association of TMB with efficacy of pembrolizumab (pembro) in patients (pts) with advanced urothelial cancer (UC): Results from KEYNOTE-045 and KEYNOTE-052
Authors: J. Bellmunt, R. de Wit, Y. Fradet, M.A. Climent, D.P. Petrylak, J-L. Lee, L. Fong, A. Necchi, C.N. Sternberg, P. Grivas, P.H. O’Donnell, T. Powles, E.R. Plimack, R. Cristescu, J. Lunceford, J. Ma, M. Rajasagi, J.L. Godwin, B.H. Moreno, D. Bajorin
Journal: Annals of Oncology (2020)
1275P Extended follow-up of DURVAST trial: A phase II study evaluating durvalumab treatment in HIV-1-infected patients with solid tumours by the Spanish lung cancer group
Authors: M. Gonzalez Cao, T. Moran, J. Dalmau, J. Garcia-Corbacho, R. Bernabe, O.J. Juan Vidal, J. de Castro Carpeño, R. Blanco, A. Drozdowskyj, A. Meyerhans, J. Blanco, J.G. Prado, B. Clotet, B. Massuti Sureda, M. Provencio Pulla, M.A. Molina-Vila, J. Martinez-Picado, R. Rosell Costa
Journal: Annals of Oncology (2020)
Covid-19: Delays in getting tests are keeping doctors from work, health leaders warn
Authors: Jacqui Thornton
Journal: BMJ (2020)

Covid-19: Delays in getting tests are keeping doctors from work, health leaders warn Jacqui ThorntonIt is getting harder for hospital doctors to get covid-19 tests quickly for themselves, according to the Royal College of Physicians (RCP), amid concerns that NHS staff absences are being caused by a lack of access to testing.
1414TiP Evaluating telisotuzumab vedotin in combination with osimertinib in patients with advanced non-small cell lung cancer: A phase I/Ib study cohort
Authors: D.R. Camidge, J.W. Goldman, G.W. Cole, Z. Sun, C.J. Ocampo, P. Komarnitsky, V. Blot
Journal: Annals of Oncology (2020)
813MO Efficacy of subsequent chemotherapy for patients with BRCA1/2 mutated platinum-sensitive recurrent epithelial ovarian cancer (EOC) progressing on olaparib vs placebo: The SOLO2/ENGOT Ov-21 trial
Authors: J-S. Frenel, J-W. Kim, D. Berton-Rigaud, R. Asher, L. Vidal, P. Pautier, J.A. Ledermann, R.T. Penson, A.M. Oza, J. Korach, T. Huzarski, S. Pignata, N. Colombo, T-W. Park-Simon, K. Tamura, G.S. Sonke, A. Freimund, C.K. Lee, E. Pujade-Lauraine
Journal: Annals of Oncology (2020)
277MO SAR439859, an oral selective estrogen receptor (ER) degrader (SERD), in ER+/ HER2- metastatic breast cancer (mBC): Biomarker analyses from a phase I/II study
Authors: S. Chandarlapaty, A. Bardia, S. Lord, H. Linden, V. Pelekanou, N. Ternes, J. Ming, V. Boutet, E. Boitier, A. Gosselin, J. Sang Lee, W. Dos-Santos Bele, A. Protopopov, M. Celanovic, A-L. Bauchet, M. Campone
Journal: Annals of Oncology (2020)
371MO Usefulness of circulating tumour DNA detection from cerebrospinal fluid in recurrent high-grade glioma
Authors: M. Fontanilles, A. Deniel, F. Marguet, L. Beaussire, N. Magne, S. Derrey, D. Richard, C. Alexandru, F. Clatot, A. Laquerrière, N. Sarafan Vasseur, F. Di Fiore
Journal: Annals of Oncology (2020)
Targeting STAT3 in Cancer Immunotherapy
Authors: Sailan Zou, Qiyu Tong, Bowen Liu, Wei Huang, Yan Tian, Xianghui Fu
Journal: Molecular Cancer (2020)

Abstract As a point of convergence for numerous oncogenic signaling pathways, signal transducer and activator of transcription 3 (STAT3) is central in regulating the anti-tumor immune response. STAT3 is broadly hyperactivated both in cancer and non-cancerous cells within the tumor ecosystem and plays important roles in inhibiting the expression of crucial immune activation regulators and promoting the production of immunosuppressive factors. Therefore, targeting the STAT3 signaling pathway has emerged as a promising therapeutic strategy for numerous cancers. In this review, we outline the importance of STAT3 signaling pathway in tumorigenesis and its immune regulation, and highlight the current status for the development of STAT3-targeting therapeutic approaches. We also summarize and discuss recent advances in STAT3-based combination immunotherapy in detail. These endeavors provide new insights into the translational application of STAT3 in cancer and may contribute to the promotion of more effective treatments toward malignancies.
290P From the CLEOPATRA study to real life: Final results from the G.O.N.O. SUPER trial
Authors: O. Garrone, T. Giarratano, A. Michelotti, C. Saggia, L. D'Onofrio, L. Merlini, E. Blondeaux, A. Beano, L. Coltelli, M.E. Cazzaniga, F. Montemurro, A. Farnesi, N.M. La Verde, A.M. Vandone, E. Collovà, L. Blasi, R. Ardito, E. DeConciliis, M. Airoldi, M.C. Merlano
Journal: Annals of Oncology (2020)
1877P Fatigue changes according to systemic therapy type in patients with advanced solid cancer
Authors: A.M. Starzer, J. Kreminger, J.M. Berger, F. Moik, M. Rauchwarter, J. Mayer, H. Haselboeck, G. Heller, M. Preusser, A.S. Berghoff
Journal: Annals of Oncology (2020)
Teams and endoscopy: another effect of the COVID-19 pandemic
Authors: Mário Dinis-Ribeiro, Cesare Hassan
Journal: Endoscopy (2020)

The quality of healthcare, and in particular gastrointestinal endoscopy, may be perceived differently both by healthcare professionals (HCPs) and by patients according to diverse perspectives or concepts [1]. Quality will vary according to different metrics, but there is usually room for improvement depending on the interventions available at different levels of the endoscopy process.
517P Early stage squamous cell carcinoma of the anal canal: Results of curative-intent therapy in a multicenter retrospective study
Authors: I.K.F. Lustosa, M.P.G. Camandaroba, B.R.S. Mattos, S.F. Silva, S. Iseas, R.S.P. Riechelmann
Journal: Annals of Oncology (2020)
LBA16 IMpassion130: Final OS analysis from the pivotal phase III study of atezolizumab + nab-paclitaxel vs placebo + nab-paclitaxel in previously untreated locally advanced or metastatic triple-negative breast cancer
Authors: L.A. Emens, S. Adams, C.H. Barrios, V.C. Dieras, H. Iwata, S. Loi, H.S. Rugo, A. Schneeweiss, E.P. Winer, S. Patel, V. Henschel, A. Swat, M. Kaul, L. Molinero, S.Y. Chui, P. Schmid
Journal: Annals of Oncology (2020)
1500TiP A phase Ib/II, multicenter, open-label, dose-escalation and dose-expansion study evaluating trastuzumab deruxtecan (T-DXd; DS-8201) monotherapy and combinations in patients with HER2-overexpressing gastric cancer (DESTINY-Gastric03)
Authors: Y.Y. Janjigian, N. Viglianti, F. Liu, A. Mendoza-Naranjo, S. Puvvada
Journal: Annals of Oncology (2020)
Influence of Prone Positioning on Electrocardiogram in a Patient With COVID-19
Authors: Hoang H. Nguyen, Richard G. Trohman, Henry D. Huang
Journal: JAMA Internal Medicine (2020)

A woman in her 50s with morbid obesity and obstructive sleep apnea presented with 3 days of fever with a temperature up to 39 °C, anosmia, and shortness of breath.Physical examination findings were significant for oxygen saturation of 85% on room air and coarse rales at the lung bases bilaterally.Chest radiography was suggestive of bilateral multifocal pneumonia.Results of a nasopharyngeal swab for coronavirus disease 2019 (COVID-19) were positive by reverse transcriptase-polymerase chain reaction.She was admitted to the intensive care unit for management.Upon admission, the patient began hydroxychloroquine and azithromycin combination therapy.On hospitalization day 2, the patient developed acute respiratory distress syndrome (ARDS) requiring intubation and mechanical ventilation.Management strategies for refractory hypoxia were not successful until she was placed in a prone position.She was maintained in a prone position for 16 hours followed by supine positioning as tolerated for 4 hours a day.Given the treatment with hydroxychloroquine and azithromycin, serial electrocardiograms (ECGs) were performed to monitor QT interval dur-ing treatment.The ECG on hospitalization day 3 (Figure 1A) showed acute changes in comparison to her prior ECG (Figure 1B).Question: What is the cause of the Q waves and low amplitudes seen in the anterior precordial leads?
Cognitive behavior therapy for internalizing disorders in children and adolescents in routine clinical care: A systematic review and meta-analysis
Authors: Gro Janne H. Wergeland, Eili N. Riise, Lars-Göran Öst
Journal: Clinical Psychology Review (2020)

Cognitive behavioral therapy (CBT) has received considerable empirical support for internalizing disorders including anxiety, depression, obsessive-compulsive disorder, and post-traumatic stress disorder in children and adolescents. However, there is less knowledge regarding how CBT performs when delivered in routine clinical care. A systematic review and meta-analysis was conducted of CBT for internalizing disorders in children and adolescents in routine clinical care. Ovid MEDLINE, Embase OVID, and PsycINFO were systematically searched for articles published until October 2019. The effectiveness of CBT, methodological quality, and moderators of treatment outcome were examined. The effects of CBT in routine clinical care were benchmarked by comparing with efficacy studies for the same disorders. Fifty-eight studies were included, comprising 4618 participants. Large effect sizes for outcome were detected at post-treatment (g = 1.28-2.54), and follow-up (g = 1.72-3.36). Remission rates across diagnoses ranged from 50.7% - 77.4% post-treatment, to 53.5% -83.3% at follow-up. Attrition rate across the disorders was 12.2%. Quality of the included studies was fair, and heterogeneity was high. Similarities between the effectiveness and efficacy studies were greater than the differences in outcome. CBT delivered in routine clinical care is efficacious in reducing internalizing disorders and symptoms. The outcomes are comparable with results obtained in efficacy studies. PROSPERO registration: ID CRD42019128709.
CMV viral load kinetics as surrogate endpoints after allogeneic transplantation
Authors: Elizabeth R. Duke, Brian D. Williamson, Bhavesh Borate, Jonathan L. Golob, Chiara Wychera, Terry Stevens-Ayers, Meei-Li Huang, Nicole Cossrow, Hong Wan, T. Christopher Mast, Morgan A. Marks, Mary E. Flowers, Keith R. Jerome, Lawrence Corey, Peter B. Gilbert, Joshua T. Schiffer, Michael Boeckh
Journal: Journal of Clinical Investigation (2020)

BACKGROUND. Viral load (VL) surrogate endpoints transformed development of HIV and hepatitis C therapeutics. Surrogate endpoints for CMV-related morbidity and mortality could advance development of antiviral treatments. Although observational data support using CMV VL as a trial endpoint, randomized controlled trials (RCTs) demonstrating direct associations between virological markers and clinical endpoints are lacking.
Psychotherapy at a Distance
Authors: John C. Markowitz, Barbara Milrod, Timothy G. Heckman, Maja Bergman, Doron Amsalem, Hemrie Zalman, Thomas Ballas, Yuval Neria
Journal: American Journal of Psychiatry (2020)

The 2020 COVID-19 pandemic has abruptly overwhelmed normal life. Beyond the fear and fatality of the virus itself comes a likely wave of psychiatric disorders. Simultaneously, social distancing has changed overnight how psychiatrists and other mental health professionals must treat patients. Telepsychotherapy, until now a promising but niche treatment, has suddenly become treatment as usual. This article briefly reviews the limited clinical evidence supporting different modes of telepsychotherapy, then focuses on how remote therapy affects clinicians and their patients.
901P Matching-adjusted indirect comparisons (MAIC) of safety between single-agent belantamab mafodotin versus selinexor plus dexamethasone in relapsed/refractory multiple myeloma (RRMM)
Authors: A. Suvannasankha, T. Prawitz, V. Kapetanakis, G. Sarri, R. Hughes, F. Wang, C. Hogea, S. Allen Ferrante, B. Gutierrez, B. Gorsh, J. Willson, R. Popat
Journal: Annals of Oncology (2020)
171P Avoid systemic overtreatment of postmenopausal breast cancer patients with ultralow MammaPrint result
Authors: M. Opdam, V. van der Noort, M. Kleijn, A. Glas, I. Mandjes, D. Kruger, P. van Diest, J.B. Vermorken, H. van Tinteren, S. Linn
Journal: Annals of Oncology (2020)
158TiP BioItaLEE: Molecular features of postmenopausal women with hormone receptor-positive (HR+), HER2-negative (HER2–) PIK3CA-mutated advanced breast cancer (ABC) on first-line treatment with ribociclib + letrozole and on second-line treatment with alpelisib + fulvestrant
Authors: G. Allegrini, M. Orditura, L. Del Mastro, C. Zamagni, R. Torrisi, V. Guarneri, I. Paris, G. Sarobba, F. Puglisi, M.A. Colleoni, F. Montemurro, A. Zambelli, M.E. Cazzaniga, M.R. Valerio, G. Bianchi, E. Romagnoli, M. Caruso, S. Cinieri, D. Castelletti, G. Arpino
Journal: Annals of Oncology (2020)
800TiP Meet-URO 12: A randomized phase II trial of niraparib versus best supportive care (BSC) as maintenance treatment in patients with locally advanced or metastatic urothelial cancer (UC) whose disease did not progress after completion of first-line platinum-based chemotherapy
Authors: F. Vignani, A. Hamzaj, U. De Giorgi, R. Tambaro, U. Basso, T. Gamba, P. Ermacora, D. Santini, S. Capacci, C. Casadei, S. Pignata, D. Bimbatti, P. Giannatempo, F. Atzori, L. Cavanna, A. Veccia, G. Scandurra, L. Doni, M. Aieta, M. Di Maio
Journal: Annals of Oncology (2020)
1208P EIT PACMAN study results: OncoSignal signaling pathway analysis using FFPE-compatible tests identifies actionable cancer targets in a variety of cancers without actionable mutations
Authors: A. Van De Stolpe, S. Neerken, E. den Biezen-Timmermans, M. Akse, S. Vermeer-van de Laar, D. van Strijp, P. Martin-Romano, M. Ngo-Camus, C. Nicotra, F. Calvo, A. Italiano
Journal: Annals of Oncology (2020)
Trends in Deescalation of Localized Breast Cancer Treatment and Caution for the Most Vulnerable Patients—A Look Back on the Decade That Was
Authors: Oluwadamilola T. Oladeru, Ariel E. Hirsch, Naomi Y. Ko
Journal: JAMA Oncology (2020)

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1127P Correlation of BRAF mutation status in circulating tumour DNA (ctDNA) with tumour biopsy and clinical outcomes in COLUMBUS
Authors: C. Robert, K.T. Flaherty, H.J. Gogas, A.M. Arance Fernandez, M. Mandala, G. Liszkay, C. Garbe, D. Schadendorf, I. Krajsova, R. Gutzmer, J.W.B. de Groot, C. Dutriaux, C. Loquai, A. Harney, E. Kiprilov, M.D. Pickard, J. Cantey-Kiser, R. Dummer, P.A. Ascierto
Journal: Annals of Oncology (2020)
459P Effect of RAS amplification (RASa) on outcomes to EGFR monoclonal antibody therapy (EGFRmAb) in metastatic colorectal cancer (mCRC)
Authors: M. Fakih, J. Lee, J.S. Sandhu, R. Madison, J. Venstrom, B. Alexander, A.B. Schrock
Journal: Annals of Oncology (2020)
1073TiP A phase I, first-in-human, multicenter, open-label, dose-escalation study of IPH5201 as monotherapy or in combination with durvalumab ± oleclumab in advanced solid tumours
Authors: J. Powderly, J.C. Bendell, B.A. Carneiro, A. Italiano, T. Macarulla Mercadé, E. Castanon Alvarez, M. Imbimbo, C. Massard, N. Mueller, A. Gascó -Hernandez
Journal: Annals of Oncology (2020)
633P Tolerability and treatment response to darolutamide (DARO) in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) in the phase III ARAMIS trial
Authors: K. Fizazi, N. Shore, M.R. Smith, T.L. Tammela, M-A. Le Berre, O. Petrenciuc, C. Zurth, I. Kuss
Journal: Annals of Oncology (2020)
1450P Efficacy and safety analysis of modified biweekly SOX regimen in the first-line treatment of advanced gastric adenocarcinoma or esophagogastric junction adenocarcinoma
Authors: S. Zhang, H. Wang, Y. Meng, X. Nie, C. Huang, F. Gao, L. Sun, Z. Liu
Journal: Annals of Oncology (2020)
1291P Hypersensitivity reactions (HR) to selpercatinib in RET fusion+ non-small cell lung cancer (NSCLC) patients (pts) following immune checkpoint inhibition (CPI)
Authors: C. McCoach, D.S.W. Tan, B. Besse, K. Goto, V.W. Zhu, C.D. Rolfo, S. Farajian, L. Potter, J.F. Kherani, V. Soldatenkova, E. Olek, P. Lee, K. Park
Journal: Annals of Oncology (2020)
Clinical characteristics, symptoms and outcomes of 1054 adults presenting to hospital with suspected COVID-19: A comparison of patients with and without SARS-CoV-2 infection
Authors: Nathan J Brendish, Stephen Poole, Vasanth V Naidu, Christopher T Mansbridge, Nicholas Norton, Florina Borca, Hang TT Phan, Helen Wheeler, Matthew Harvey, Laura Presland, Tristan W Clark
Journal: Journal of Infection (2020)

Most reports describing the characteristics of patients hospitalised with COVID-19 lack a comparator group. We compared clinical characteristics, symptoms, and outcomes of adults presenting to hospital during the pandemic first wave, who tested positive and negative for SARS-CoV-2.Detailed patient data was obtained from a large, controlled, non-randomised trial of molecular point-of-care testing versus laboratory RT-PCR for SARS-CoV-2 in adults presenting to a large UK hospital with suspected COVID-19.1054 patients were included: 352 (33.4%) tested positive and 702 (66.6%) negative. 13.4% (47/352) COVID-19-positive patients had COPD versus 18.7% (131/702) of COVID-19-negative patients (difference=5.3% [95%CI -9.7% to -0.5%], p = 0.0297). 5.7% (20/352) of COVID-19-positive patients were smokers versus 16.5% (116/702) of negative patients (difference=-10.8% [-14.4% to -7.0%], p = 0.0001). 70.5% (248/352) of COVID-19-positive patients were White-British versus 85.5% (600/702) of negative patients (difference=-15.0% [-20.5% to -9.7%], p<0.0001). 20.9% (39/187) of COVID-19-positive patients were healthcare workers versus 5.2% (15/287) of negative patients (p<0.0001). Anosmia was reported in 33.1% (47/142) versus 8.8% (19/216) of COVID-19-positive and negative patients respectively (p<0.0001). Non-SARS-CoV-2 respiratory viruses or atypical bacteria were detected in 2.5% (5/197) of COVID-19 patients versus 7.9% (24/302) of COVID-19-negative patients (p = 0.0109). Hospitalisation duration and 30-day-mortality were higher in COVID-19 patients and invasive ventilation was more frequent (11.1% vs 2.8%, p<0.0001), and longer (14.5 vs 4.7 days, p = 0.0015).There were substantial differences between patients with and without COVID-19 in terms of ethnicity, healthcare worker-status, comorbidities, symptoms, and outcomes. These data can inform healthcare planning for the next phase of the pandemic.