tbuckley/cabot-search huggingface dataset:
Abstract PO-051: Intracellular delivery of nuclear localization signal suppresses COVID-19 mediated inflammation by regulating expression of cytokines/chemokines
Authors: Danbi Lee, Sanghyeon Yu, Misuk Baek, Jieun Kim, Mingu Kang, Hakyoung Park, Jaewook Lee, Seokwon Lee, Junghun Kwak, Hyemin Yu, Seungwoo Lee, Sujeong Kim, Hyewon Lee, Dasom Shin, Boram Kim, Minyoung Jung, Youngsil Choi, Daewoong Jo, Gyunam Kim, Dongho Kim
Journal: Clinical Cancer Research (2020)

Abstract The outbreak of coronavirus disease 19 (COVID-19), caused by the recently identified coronavirus named SARS-CoV-2, is leading patients to death (mortality: ~7%) because of cytokine storm. COVID-19 induces excessive secretion of proinflammatory cytokines and chemokines accompanied by the disruption of the bronchi and alveoli, which could ultimately develop into permanent lung impairments such as pulmonary fibrosis. To regulate the uncontrolled expression of proinflammatory cytokines/chemokines, improved cell-permeable nuclear import inhibitor (iCP-NI) has been developed by fusing sequence-optimized hydrophobic cell-penetrating peptide (CPP), namely advanced macromolecule transduction domain (aMTD) with nuclear localization signal (NLS) of stress responsive transcription factors (SRTFs: NF-κB, STAT1/3, AP-1, and NFAT). Intracellularly delivered NLS is supposed to suppress expression of proinflammatory cytokines/chemokines by inhibiting transport of SRTFs from cytoplasm into nucleus. iCP-NI regulated expression of cytokines (TNF-α: -79%, IL-6: -91%, IL-12: -110% and IL-10: +574%) and chemokines (MCP-1: -89%) in bronchoalveolar lavage fluids (BALFs) from RNA virus infection mimetic pneumonitis animals that were induced with inhalation of RNA structure molecule, poly I:C. iCP-NI also significantly decreased pulmonary fibrosis (-61%) in bleomycin-induced pulmonary fibrosis animals. Moreover, iCP-NI protected leukocytes (CD3+ T cell: 100%, CD4+/CD3+ T cell: 96%, B220+ B cell: 85%, CD45+ macrophage: 100%) and reduced apoptotic splenocytes (-97%) in staphylococcal enterotoxin B (SEB) and poly I:C-induced acute pneumonitis animals. These results suggest that iCP-NI has potential as a novel therapeutic measurement for inflammation caused by various infectious diseases including COVID-19 accompanied with cytokine storm and severe sepsis. Citation Format: Danbi Lee, Sanghyeon Yu, Misuk Baek, Jieun Kim, Mingu Kang, Hakyoung Park, Jaewook Lee, Seokwon Lee, Junghun Kwak, Hyemin Yu, Seungwoo Lee, Sujeong Kim, Hyewon Lee, Dasom Shin, Boram Kim, Minyoung Jung, Youngsil Choi, Daewoong Jo, Gyunam Kim, Dongho Kim. Intracellular delivery of nuclear localization signal suppresses COVID-19 mediated inflammation by regulating expression of cytokines/chemokines [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-051.
Abstract A15: New treatment opportunities by in vivo and in vitro screening approaches in melanoma
Authors: Federica Marocchi, Letizia Granieri, Fiorenza Lotti, Fernando Palluzzi, Jole Costanza, Laura Riva, Daniela Bossi, Luisa Lanfrancone
Journal: Cancer Research (2020)

Abstract Treatment of metastatic melanoma has been recently revolutionized by the use of targeted and immune inhibitors, though efficiently working only in a fraction of patients. Adverse effects still represent major challenges, as well as the rapid development of drug resistance upon treatment, thus suggesting that it is of utmost importance to elucidate additional molecular pathways and targets to better understand the biology of this tumor. In vivo RNAi screens done in patient-derived xenografts (PDXs) that fully phenocopy the original tumor of the patient represent a powerful tool to identify new putative essential and druggable candidates, and to repurpose drugs already approved for other indications. To this end we have recently generated a platform of melanoma PDXs with which we can recapitulate both melanoma growth and metastasization. We have performed in vivo shRNA screens, where we have found numerous and patient-specific epigenetic genes essential for tumor growth in vivo. With this platform, we have isolated novel frailties whose depletion favors cell senescence. Preliminary data using shRNA libraries of actionable genes for which drugs are already available suggest that specific drugs can be repurposed for melanoma treatment. We have proved that this approach can work in vivo, and we propose to convert it in an in vitro assay to rapidly translate new discoveries to the patient. Note: This abstract was not presented at the conference. Citation Format: Federica Marocchi, Letizia Granieri, Fiorenza Lotti, Fernando Palluzzi, Jole Costanza, Laura Riva, Daniela Bossi, Luisa Lanfrancone. New treatment opportunities by in vivo and in vitro screening approaches in melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr A15.
Combining two implementation strategies to increase reach for tobacco treatment with cancer patients: Ask-Advise-Connect and closing care gaps.
Authors: Terri Wolf, Elisa Tong, Susan L Stewart, Moon Chen
Journal: Journal of Clinical Oncology (2020)

242 Background: Tobacco treatment is an important component of cancer care, and pragmatic strategies are needed. The University of California Davis Comprehensive Cancer Center (UCD CCC) was selected to join the National Cancer Institute Cancer Center Cessation Initiative (NCI C3I) to integrate tobacco treatment with cancer care. As a matrix cancer center, UCD had tobacco treatment workflows established in primary care, with Health Management Education group classes and a quitline order, but less so in cancer care. Methods: We use the RE-AIM framework for our study evaluation. During the two-year study period (1/2018-12/2019) patient data were reported in 6-month periods to NCI C3I from core Cancer Center clinics including medical, surgical, and radiation oncology. Three strategies were implemented serially and in convergence. Strategy #1 involved cancer provider and staff education and training, Strategy #2 initiated the Ask-Advise-Connect workflow with medical assistants assessing and referring within the clinic encounter, and Strategy #3 conducted Closing Care Gaps outreach to contact “unassisted” smokers outside of the clinic encounter. Stakeholder perspectives for implementation readiness across units were engaged at least bi-monthly by multidisciplinary members of the Cancer Committee, led by the physician-in-chief. Implementation strategies were developed in partnership with clinic management and Health Management Education staff with monthly rapid feedback reports for referral orders. Results: Our project Reach improved tobacco assessment from 83.6% to 96.4% and tobacco treatment program orders and outreach by 6-fold (from 40 to 254) over the four NCI C3I 6-month reporting periods. For tobacco treatment program Effectiveness, among 118 patients who engaged in treatment (January 2018-June 2019), past-week abstinence at 6 months was 22.9% (missing data assumed to be smoking) Adoption and Implementation of tobacco treatment program referrals were highest in medical (5-10 fold) and surgical oncology (3-fold) annual increases. In contrast, radiation oncology referrals remained low due to a different clinic workflow and electronic health record module. Booster trainings have helped to Maintain referrals in the clinic. Conclusions: A matrix cancer center can rapidly adopt and implement tobacco treatment strategies that are internal and external to the clinic visit, with the goal of offering tobacco treatment and maximizing reach to all cancer patients who smoke.
Variations in recommended surveillance in colorectal cancer survivorship care plans.
Authors: Alaina Chodoff, Katherine Clegg Smith, Aishwarya Shukla, Amanda L. Blackford, Nita Ahuja, Fabian McCartney Johnston, Kimberly S. Peairs, Justinian R. Ngaiza, Tam Warczynski, Brenda Nettles, Eden Stotsky-Himelfarb, Adrian Gerard Murphy, Nancy Mayonado, Jennifer DeSanto, Claire Frances Snyder, Youngjee Choi
Journal: Journal of Clinical Oncology (2020)

13 Background: Survivorship care plans (SCPs) outline pertinent information about a cancer survivor’s treatment and follow-up care. We describe the content of colorectal cancer (CRC) SCPs, completed as part of a randomized controlled trial of SCPs, and evaluate whether follow-up recommendations are guideline concordant. Methods: We analyzed 74 CRC SCPs from an academic and community cancer center. Frequency distributions and descriptive statistics were calculated for the entire cohort and separately by recruiting site. Follow-up recommendations were compared to American Cancer Society (ACS), American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) guidelines (Table). Results: Content routinely provided in SCPs (&gt;80%) included patient demographics, cancer diagnosis, treatment details (surgery, chemotherapy, radiation therapy) as well as treatment-related side effects. SCP content specified less frequently included cancer stage, cancer risk (predisposing conditions), and recommendations for genetic counseling/testing and health promotion. Nearly all SCPs from the community site provided uniform, guideline-concordant follow-up. At the academic site, on average, more than 15 follow-up recommendations were listed for each surveillance modality, except colonoscopy. Among the SCPs that specified the frequency of follow-up care, the rate of guideline-concordant recommendations was 15/42 (36%) for follow-up visits, 29/43 (67%) for imaging, 12/45 (27%) for laboratory and 39/39 (100%) for colonoscopy. Conclusions: SCPs consistently provided information about CRC diagnosis and treatment, but often omitted information about cancer risk, staging and prognosis. There was considerable variation between cancer centers in the follow-up recommendations suggested for CRC survivors. Future work to improve the consistency of SCP follow-up recommendations with guidelines may be needed. Clinical trial information: NCT03035773 . [Table: see text]
Process of the integration of patient advisors in oncology: Patient advisors' views.
Authors: Marie-Pascale Pomey, Marie-France Vachon, Danielle Charpentier, Marie-Andrée Côté, Mado Desforges, Karine Bouchard, Cécile Vialaron, Monica Iliescu-Nelea, Louise Normandin
Journal: Journal of Clinical Oncology (2020)

54 Background: Since 2017, in Quebec (Canada), a research project is focusing on the feasibility, the processes, and the contribution of integrating patients who have already had cancer experiences (named patient advisors (PA)) in the oncology clinical team. In fact, the trained PA meet patients in health care settings in addition to the other health professionals in order to improve health care and partnership between professionals and patients. This presentation communicates the PA’s perception of their contribution and the factors influencing implementation of these programs in 4 establishments. Methods: Between April and May 2020, semi-structured virtual interviews lasting about 60 minutes were conducted on 12 patient advisors involved since 2017 in the elaboration of these support programs. The interviews were recorded and transcribed completely. The data analysis was done with content analysis using the QDA Miner 5.0 software, applying the qualitative analysis quality standards. Results: First of all, the 12 PAs have reported that the accompaniment of 67 patients have allowed them to share their experiential knowledge not only related to living with the illness but also about healthcare organization and the anticipation of treatments. They also highlighted their capacity to share situations that can be improved by healthcare professionals (example: wait times for exams; patients’ difficulty in understanding their illness, etc). However, they also highlighted 4 factors which limit the implementation: 1) organizational (the unclear and changing nature of the breast cancer consultation schedule, difficulty of access to consultation rooms and unsuitable schedules for the PA’s reality.; 2) leadership (lack of clinicians promoting the intervention; managers’ low involvement; lack of clarity of roles); 3) human (work overload and employee turnover); 4) PA’s status (lack of compensation and of recognition). Also, to optimize their integration, the PA’s suggest to work on a lasting bond of trust with the professionals, the creation of a status recognized by health establishments, the recognition of their role by the clinical team, to give them access to physical spaces, and an openness of the teams to their complementary knowledge. Conclusions: These first results suggest the importance during the implementation of such programs of working proactively with the PAs and the professionals on organization, leadership, resources, and status factors to allow the people dealing with cancer to benefit from experiential knowledge of other patients within their clinical team.
Effect of time to treatment and comprehensive care at commission on cancer-accredited practices on survival in rural patients with colorectal cancer.
Authors: Suneel Deepak Kamath, Katherine Tullio, Wei Wei, Gregory S. Cooper, Alok A. Khorana
Journal: Journal of Clinical Oncology (2020)

109 Background: Rural cancer care in the United States has unique challenges from variable access to care. This study examined differences in time to first treatment (TTT), a surrogate for access, and predictors of overall survival (OS) between rural and non-rural colorectal cancer (CRC) patients. Methods: Patients with stage I-III CRC from 2004-2012 in the National Cancer Database of Commission on Cancer (CoC)-accredited facilities were included and categorized into rural and non-rural groups. Differences in demographic, disease characteristics, socioeconomic (SE) factors and TTT (&lt; 4 weeks, 4-8 weeks and &gt; 8 weeks) between rural and non-rural patients were assessed by Chi-square test. The effect of demographics, SE factors, and TTT on OS were assessed using Cox models. Results: The study population comprised 605,913, 11,649 (2%) of whom were rural. Compared to non-rural patients, rural patients were more likely to be age &gt; 65, male, Caucasian, receive care at non-academic centers, have government insurance, have lower income and less education (p&lt;0.0001 for all). Significant demographic and SE differences are shown in Table. Rural patients had similar mean TTT compared to non-rural patients (2.76 vs. 2.84 weeks, p = 0.35). Slightly more rural patients had TTT &lt; 4 weeks (77% vs. 75%, p &lt;0.0001). Shorter TTT (both &lt;4 weeks vs. 8 weeks and 4-8 weeks vs. &gt; 8 weeks) was associated with improved OS (HR: 0.87, 95% CI: 0.85-0.89, p&lt;0.0001 and HR: 0.74, 95% CI: 0.73-0.76, p&lt;0.0001, respectively). After adjusting for demographic, disease and SE factors, rural status was associated with modestly better OS compared to non-rural status (HR: 0.96, 95% CI: 0.92-0.99, p=0.006). Conclusions: Despite several adverse demographic and socioeconomic factors, rural CRC patients had modestly better OS compared to non-rural patients. Rural and non-rural CRC patients had similar TTT in this cohort. These data suggest the comprehensive cancer care delivered by CoC-accredited practices is associated with rapid TTT and improved OS in rural CRC patients. It is unclear whether our data apply to non-CoC-accredited facilities in rural United States. [Table: see text]
Early response evaluation using primary tumor and nodal imaging features to predict progression-free survival of locally advanced non-small cell lung cancer
Authors: Nasha Zhang, Rachel Liang, Michael F. Gensheimer, Meiying Guo, Hui Zhu, Jinming Yu, Maximilian Diehn, Bill W Loo, Ruijiang Li, Jia Wu
Journal: Theranostics (2020)

Prognostic biomarkers that can reliably predict early disease progression of non-small cell lung cancer (NSCLC) are needed for identifying those patients at high risk for progression, who may benefit from more intensive treatment. In this work, we aimed to identify an imaging signature for predicting progression-free survival (PFS) of locally advanced NSCLC. Methods: This retrospective study included 82 patients with stage III NSCLC treated with definitive chemoradiotherapy for whom both baseline and mid-treatment PET/CT scans were performed. They were randomly placed into two groups: training cohort (n=41) and testing cohort (n=41). All primary tumors and involved lymph nodes were delineated. Forty-five quantitative imaging features were extracted to characterize the tumors and involved nodes at baseline and mid-treatment as well as differences between two scans performed at these two points. An imaging signature was developed to predict PFS by fitting an L1-regularized Cox regression model. Results: The final imaging signature consisted of three imaging features: the baseline tumor volume, the baseline maximum distance between involved nodes, and the change in maximum distance between the primary tumor and involved nodes measured at two time points. According to multivariate analysis, the imaging model was an independent prognostic factor for PFS in both the training (hazard ratio [HR], 1.14, 95% confidence interval [CI], 1.04-1.24; P = 0.003), and testing (HR, 1.21, 95% CI, 1.10-1.33; P = 0.048) cohorts. The imaging signature stratified patients into low- and high-risk groups, with 2-year PFS rates of 61.9% and 33.2%, respectively (P = 0.004 [log-rank test]; HR, 4.13, 95% CI, 1.42-11.70) in the training cohort, as well as 43.8% and 22.6%, respectively (P = 0.006 [log-rank test]; HR, 3.45, 95% CI, 1.35-8.83) in the testing cohort. In both cohorts, the imaging signature significantly outperformed conventional imaging metrics, including tumor volume and SUVmax value (C-indices: 0.77-0.79 for imaging signature, and 0.53-0.73 for conventional metrics). Conclusions: Evaluation of early treatment response by combining primary tumor and nodal imaging characteristics may improve the prediction of PFS of locally advanced NSCLC patients.
Pleural Fluid with Hooklets in a 7-Year-Old Boy with Severe Multisystem Cystic Echinococcosis
Authors: Patrick M. Meyer Sauteur, Sasha J. Tharakan, Christa Relly, Felicia Drack, Ralph A. Schmid, Kevin Schmid, Alexander Moeller, Ralph Gnannt, Christoph Berger, Ueli Moehrlen
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

normal level of activity but exertional dyspnea, re-expansion of the right lower lobe, and reduction in the size of the liver cyst.Cystic echinococcosis is a very rare disease in children but may be considered as differential diagnosis of pneumonia with pleural effusion in migrant children from endemic areas (3-5).Even though the incubation period lasts for years also young children can be affected (3).Our case further highlights that symptoms in children may be sparse or lacking despite enormous mass effect of cysts (3).Hooklets on microscopy can be clues to diagnosis (6, 7).Importantly, spillage of protoscoleces should be avoided to prevent anaphylaxis and severe immunological reactions (8).
Liver-lung axes in alcohol-related liver disease
Authors: Gavin E. Arteel
Journal: Clinical and Molecular Hepatology (2020)

Alcohol-related liver disease (ALD) and alcohol-related susceptibility to acute lung injury are the leading causes of morbidity and mortality due to chronic alcohol abuse. Most commonly, alcohol-induced injury to both organs are evaluated independently, although they share many parallel mechanisms of injury. Moreover, recent studies indicate that there is a potential liver lung axis that may contribute to organ pathology. This mini-review explores established and potential mechanisms of organ-organ crosstalk in ALD and alcohol-related lung injury.
Treatment with tocilizumab does not inhibit induction of anti-COVID-19 antibodies in patients with severe SARS-CoV-2 infection
Authors: Alexandra Cabanov, Blake A. Flood, Jeffrey Bloodworth, Emily F. Higgs, Jessica Fessler, Michael Y. K. Leung, Kyle R. Cron, Jonathan Trujillo, Athalia R. Pyzer, Sherin Rouhani, Garth Strohbehn, Brian Heiss, Mark Ratain, Pankti Reid, Kiang-Teck J. Yeo, Randy F. Sweis, Yuanyuan Zha, Thomas F. Gajewski
Journal: Clinical Cancer Research (2020)

Tocilizumab (TCZ), an interleukin-6 (IL-6) receptor-blocking monoclonal antibody, is used to treat variousrheumatologic conditions and cytokine release syndrome in CAR-T cell therapy and has been repurposed to treatCOVID-19-related hyperinflammation  There are limited data available reporting how TCZ affects the immuneresponse in the context of COVID-19  To investigate this question, we recruited patients treated with TCZ as part ofa COVID-19 biobanking protocol (A-28063295) to study immune parameters that might be affected  We enrolled 19patients who were treated with a range of 40-200mg TCZ as part of a low-dose TCZ trial (COVIDOSE, reportedseparately as abstract A-94803796), and 11 patients who received 400mg TCZ on a standard-of-care expanded-access basis  As IL-6 acts as a stimulant of B-cell proliferation, plasma cell maturation, and antibody responses, weevaluated whether blocking the IL-6 receptor with TCZ therapy impairs antibody generation to SARS-CoV-2  Toevaluate antibody levels in these patients, we performed ELISAs against the SARS-CoV-2 spike glycoprotein and itsreceptor-binding domain (RBD)  The spike glycoprotein, a structural protein of SARS-CoV-2, is a crucial componentin the recognition, attachment, and entry of the virus into host cells  Specifically, the RBD is responsible for bindingthe ACE2 receptor on human cells, and likely serves as a major target for neutralizing antibodies  To establish if theformation and persistence of antibodies was affected by TCZ treatment, we analyzed serum and plasma sampleslongitudinally from 29 patients treated with TCZ and 26 control patients  To account for potential variability betweenplates, the measured optical density (OD) values were normalized to the OD for COVID-19-negative control serumat 1:50 dilution, and the same negative control was tested on each plate  Titers were calculated as the linearinterpolation of the inverse dilution at which the normalized OD value crossed a threshold of 1, representing themaximum OD measured for the negative control  Anti-spike and anti-RBD antibodies increased significantly overtime in both TCZ-treated patients and controls (p < 0 005 for both)  Increasing antibody titers throughout the diseasecourse followed a similar trajectory in TCZ-treated patients compared to control patients, suggesting that TCZtreatment does not impede the generation of antibodies to SARS-CoV-2  Additionally, TCZ-treated patients achievedcomparable maximal observed antibody titers to control patients (average maximal log10 (titer) of 5 42 and 4 96 forspike and of 4 39 and 4 44 for RBD, respectively)  These data suggest that TCZ does not impair the induction ofanti-SARS-CoV-2 antibodies