tbuckley/cabot-search huggingface dataset:
Abstract 5654: Affinity tuned Xmab®2+1 anti-mesothelin x anti-CD3 bispecific antibody induces selective T cell-dependent cellular cytotoxicity of human ovarian cancer cells
Authors: Veronica G. Zeng, Matthew S. Faber, Matthew J. Bernett, Kendra N. Avery, John L. Zeytounian, Rumana Rashid, Umesh S. Muchhal, Gregory L. Moore, John R. Desjarlais, Michael Hedvat
Journal: Cancer Research (2020)

Abstract Mesothelin (MSLN) is a tumor-associated antigen highly expressed in ovarian tumors. Current treatment options for ovarian cancer have only modest efficacy and there remains a large unmet need for new targeted therapies. We generated targeted T cell engager bispecific antibodies that bind MSLN on tumor cells and CD3 on T cells. The humanized and affinity-optimized MSLN x CD3 bispecific antibodies are in an XmAb® 2+1 Fab2-scFv-Fc format that bind bivalently to MSLN and monovalently to CD3. The affinity of the MSLN-targeting arms was reduced to promote avid binding to MSLN expressing cancer cell lines and to minimize reactivity on normal surrogate cell lines. We correlated the expression of MSLN on cancer cell lines to 191 biopsy cores of serous and mucinous ovarian cancer tissues by IHC to identify surrogate cell lines to test for T cell-dependent cellular cytotoxicity (TDCC) activity. MSLN-transfected A549 cells were found to stain as intensely as ovarian cancer tumors expressing high amounts of MSLN. OVCAR-8 cancer cells were found to correlate with a medium MSLN level density on ovarian cancer tumors while ASPC-1 cells represented low MSLN-expressing tumors. Finally, we correlated expression of MSLN to non-cancer adjacent tissues and identified SKOV3, HT29, MCF7, and A549 (parental) cancer cells as appropriate surrogates of normal tissues. Reduction of MSLN affinity of MSLN x CD3 XmAb® 2+1 bispecific antibodies led to preferential killing of MSLN-high target cells, with up to 45-fold more potent TDCC activity on OVCAR8 and ASPC-1 cancer cells compared to the selected normal surrogate cell lines. Engineering of selective MSLN x CD3 bispecific antibodies allows for preferential killing of cancer cells, potentially minimizing on-target/off-tumor effects that may contribute to dose-limiting toxicities. Citation Format: Veronica G. Zeng, Matthew S. Faber, Matthew J. Bernett, Kendra N. Avery, John L. Zeytounian, Rumana Rashid, Umesh S. Muchhal, Gregory L. Moore, John R. Desjarlais, Michael Hedvat. Affinity tuned Xmab®2+1 anti-mesothelin x anti-CD3 bispecific antibody induces selective T cell-dependent cellular cytotoxicity of human ovarian cancer cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5654.
Abstract LB-163: Cost-effectiveness analysis of HBV-related hepatocellular carcinoma screening in cirrhosis patients with antiviral treatment in China
Authors: Meng Zhang, Yaoguang Li, Shunxiang Zhang, Jianying Zhang
Journal: Cancer Research (2020)

Abstract Background/Aims: The majority of hepatocellular carcinoma (HCC) patients (&amp;gt;80%)are attributable to hepatitis B virus (HBV) in China. Antiviral treatment is a public health strategy to slow down or change the progression of the disease so as to prevent HCC. In recent years, the Chinese government has been reducing the price of antiviral drugs responding to WHO program of global hepatitis B elimination. Therefore, we modelled the consequences of different screening strategies with or without antiviral treatment to evaluate the cost-effectiveness for HBV-related cirrhosis patients in China. Methods: We designed a markov model to compare no screening with 8 screening strategies in HBV-related cirrhosis patients aged 40 and older in China: annual/semiannual US, annual/semiannual US with AFP, annual/semiannual CT and annual/semiannual MRI. Meanwhile, to evaluate the cost-effectiveness of the strategies in the combination of screening and the antiviral treatment, we also assessed the other 8 screening strategies with antiviral treatment compared to the 8 non-antiviral strategies accordingly. Costs, quality-adjusted life-years (QALYs), life-years (LY) and incremental cost-effectiveness ratios (ICERs) were collected and used to assess the cost-effectiveness of screening strategies and antiviral therapeutics. Results: Semiannual CT strategy was less cost and more effective than no screening with 0.81 QALYs gained and $1092 saved. The ICER ($/QALY) for semiannual MRI strategy compared with semiannual CT strategy was $220,318 that was higher than the WTP ($29,331/QALY). As to antiviral treatment strategies, Semiannual CT strategy was also less cost and more effective than no screening with 0.48 QALYs gained and $535 saved. Not only was Semiannual CT the most efficacious strategy, but also the ICERs ($/QALY) were $4,681/QALY, $6,814/QALY and $11,560/QALY as the results by comparing annual US with AFP strategy, annual CT strategy and semiannual US with AFP strategy to semiannual CT strategy respectively. The QALY of semiannual CT with antiviral treatment increased by 5.37 compared to semiannual CT without antiviral treatment. The ICER was $3,944/QALY. Conclusions: Antiviral treatment appears to be a cost-effective strategy in HBV-related cirrhosis populations in China and semiannual CT with antiviral treatment strategy may be more cost-effective for HBV-related hepatocellular carcinoma Screening and prevention. Citation Format: Meng Zhang, Yaoguang Li, Shunxiang Zhang, Jianying Zhang. Cost-effectiveness analysis of HBV-related hepatocellular carcinoma screening in cirrhosis patients with antiviral treatment in China [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-163.
Abstract 3205: classifieRc: An interactive web interface for the molecular classification of colorectal cancer from RNA-sequencing data
Authors: Gerard Quinn, Tamas Sessler, Wendy Allen, Sarah Maguire, Philip Dunne, Darragh McArt, Harper VanSteenhouse, Peter Gallagher, Andrea Lees, Dan Longley, Bruce Seligmann, Mark Wappett, Simon McDade
Journal: Cancer Research (2020)

Abstract Background: Transcriptional predictors are increasingly important for sub-typing cancer patients and understanding disease aetiology, predicting patient outcomes and response to treatment. Colorectal cancers (CRC) can be classified by transcriptionally inferred consensus (CMS) and intrinsic (CRIS) sub-types, annotating transcriptional profiles derived from colorectal cancer samples with these sub-types and other transcriptionally inferred predictors requires an experienced bioinformatician and is time-consuming. Methods: Publically available R packages CMSclassifier, CRISclassifier, MCP-counter and DoRothEA have been integrated into a web interface using the R/Shiny framework which allows users to upload gene expression data which can be additionally normalized with DESeq2. Visualization of this data can be interacted with through using plotly. Results: To address this bottleneck, we developed the classifieRC Shiny app, which enables rapid analysis, annotation of colorectal cancer transcriptional profiles with state-of-the-art transcriptional CRC sub-typing (CMS and CRIS) as well as estimation of cellular composition (MCP-Counter) and transcription factor activity predictions (DoRothEA). classifieRC can be accessed through a web-based interface, a locally deployable R-script or executable software, with capability of publishing datasets and their resulting analysis to Shiny.IO. Conclusions: classifieRc enables researchers to rapidly annotate colorectal transcriptomic datasets with molecular sub-types and of functional predictions without the need for a dedicated bioinformatician, expediting insights related patient cohort analyses and novel discoveries. classifieRc provides an easy to use flexible framework for functional annotation transcriptomic datasets and a platform for development of other disease specific apps. Citation Format: Gerard Quinn, Tamas Sessler, Wendy Allen, Sarah Maguire, Philip Dunne, Darragh McArt, Harper VanSteenhouse, Peter Gallagher, Andrea Lees, Dan Longley, Bruce Seligmann, Mark Wappett, Simon McDade. classifieRc: An interactive web interface for the molecular classification of colorectal cancer from RNA-sequencing data [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3205.
Abstract 4891: Hepatitis B virus remodels host protein interaction networks to generate distinct cellular dependencies
Authors: John D. Gordan, Adriana Pitea, Manon Eckhardt, Gwendolyn Jang, Rigney E. Turnham, Alex L M. Choi, John Von Dollen, Huat C. Lim, Elizabeth F. Thayer, R. Katie Kelley, Danielle L. Swaney, Wei Zhang, Fabian J. Theis, Trey Ideker, Nevan J. Krogan
Journal: Cancer Research (2020)

Abstract Hepatocellular carcinoma (HCC) is the second leading cause of cancer death worldwide. Advanced HCC has proven particularly difficult to treat because of a scarcity of clear genetic drivers of cancer progression; thus, there are currently no predictive markers that guide HCC therapy. HCC arises in the context of co-morbid hepatitis due to hepatitis B virus (HBV), hepatitis C (HCV) or fatty liver disease. We hypothesize that protein-protein interactions (PPIs) between viral proteins and HCC genes may contribute to tumor initiation and maintenance. In order to characterize these PPIs, we performed affinity purification - mass spectrometry (APMS), defining 145 HBV/host PPIs including known and novel interacting partners. We next used a network propagation algorithm to identify host genes and protein complexes that were preferentially mutated in the absence of HBV infection. HBV is a small DNA virus, with 4 genes of which only one has enzymatic activity, raising a question as to how HBV interaction modifies host behavior. Using AP-MS of host proteins, we found that the HBV X protein (HBx) remodels multiple host protein complexes through direct interaction. These physical effects on complex components result in distinct biochemical behavior from the CRL4 E3 ubiquitin ligase complex as well as the phosphatase PP2A, as determined through global phosphoproteomics and ubiquitin analysis. We show that this remodeling driven by HBx substantially changes cellular protein turnover and downstream signaling dynamics. We followed this up with assessments of cellular viability and proliferation in response to pharmacological inhibition or CRISPRi-based knockdown of HBx effectors. Our data support a model where HBV proteins alter the components and behavior of key regulatory protein complexes in the cell, altering tumor behavior and raising the possibility of precision therapeutics for HCC. Citation Format: John D. Gordan, Adriana Pitea, Manon Eckhardt, Gwendolyn Jang, Rigney E. Turnham, Alex L M. Choi, John Von Dollen, Huat C. Lim, Elizabeth F. Thayer, R. Katie Kelley, Danielle L. Swaney, Wei Zhang, Fabian J. Theis, Trey Ideker, Nevan J. Krogan. Hepatitis B virus remodels host protein interaction networks to generate distinct cellular dependencies [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4891.
Abstract 807: Predictive biomarkers for Bevacizumab activity in recurrent glioblastoma: A single institution study
Authors: Marcin Dragan, Matthew Carli, Mark Malkin, Victor Yazbeck
Journal: Cancer Research (2020)

Abstract Glioblastoma Multiforme (GBM) is an aggressive type of astrocytoma and the most common malignant brain tumor in adults. Bevacizumab is a recombinant monoclonal antibody that targets VEGF-A. VEGF is regulated by the hypoxia-inducible-factor (HIF-1α) pathway, with the tumor suppressor gene TP53 as one of the key regulating factors. Our study examines the relevance of various genetic mutations of the HIF-1α pathway and their predictive significance in patients diagnosed with recurrent GBM and treated with bevacizumab. A total of 41 patients diagnosed with recurrent GBM and treated with Bevacizumab at Virginia Commonwealth University from January 1990 through November 2018 were included in our study. Our study cohort consists of 56.1% males and 43.9% females, with an average age of 59.9 (SD 12.1), and 68.3% were Caucasian. The majority (90%) of the cohort were classified as de novo cases of GBM. The overall survival (OS) was 172.5 days (95% CI: 122.0, 218.5), with a minimum of 11 days and maximum of 904 days measured from the date of the first bevacizumab treatment to the date of death. The majority of patients (70.7%) responded to treatment, with 61% exhibiting a partial response and 9.8% exhibiting a complete response. The median first response to treatment (FRT) was 34 days (95% CI: 21, 40), with a minimum of 2 days and maximum of 76. All patients died during the follow-up period. Survival analyses for OS, along with FRT, were both performed with Kaplan-Meier curves generated individually. We have examined the clinical characteristics of our study cohort and are currently examining the genetic characteristics of the tumors in our cohort. At the time of the conference we will have updated genomic and radiographic data in addition to the current detailed clinical data. Citation Format: Marcin Dragan, Matthew Carli, Mark Malkin, Victor Yazbeck. Predictive biomarkers for Bevacizumab activity in recurrent glioblastoma: A single institution study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 807.
FRI0230 Clinical presentation of 475 patients with primary sjÖgren’s syndrome who where seen by the rheumatologists
Authors: C Diaz, C Geli, C Diaz-Torne, H Corominas, M Moreno, A Rodriguez, JM Llobet, G Vazquez
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> Study the clinical presentation of primary Sjögren's syndrome (pSS) patients in a rheumatology unit. <h3>Methods</h3> 475 patients with pSS have been studied. European criteria was used for the diagnostic. Patients with primary biliary cirrhosis and hepatitis C were excluded. Demografic, clinical and laboratory data were taken following the protocol of the unit. Minor salivary biopsy was carried out on 90% of the patients. <h3>Results</h3> 94.5% were women. Age was 63 ± 12. Years of evolution were 10 ± 13. More prevalent extraglandular manifestations were: Carpal tunnel's syndrome (CTS), 40%; fibromialgy, 36%; intermitent non inflammatory arthritis, 36%; inflammatory osteoarthritis, 10%; thyroid's disfunction, 25.4%; photosensibility, 20%; peripheric neurologic manifestations without CTS, 5%; central neurologic manifestations, 5%; haematological manifestations, 8; renal manifestations, 5%; vasculitis, 13%. Rheumatoid factor (RF) was positive in 50% of the patients, ANA in 70%, antithyroidal antibodies in 27%, SS-A/Ro in 23% and SS-B/La in 11%. 37% of them come because of rheumatic manifestations, (14% fibromialgy, 14% arthritis, 5% inflammatory osteoarthritis, 4% Raynaud´s phenomenom, another 5% are athralgia and low back pain.) 30.5% come because of oral or ocular dryness and parotidomegalia. Other reasons for consultatioon were: autoinmmune cytopenia (5%), thyroidal disfunctions (3%), vasculitis (2%), and RF or ANA (2%). <h3>Conclusion</h3> The most common reason for consultation were rheumatic manifestations. The second reason was the oral and ocular dryness. Analitical alterations (Cytopenias, RF, ANA) can be other reasons for consultation.
COVID-19 as a barrier to attending for gastrointestinal endoscopy: weighing up the risks
Authors: Colin J Rees, Matt D Rutter, Linda Sharp, Bu Hayee, James E East, Pradeep Bhandari, Ian Penman
Journal: The Lancet. Gastroenterology & hepatology (2020)

unprecedented challenges imposed by the current pandemic on all aspects of our lives, centres across the globe were able to work together to collect and analyse detailed outcome data for more than 700 patients with SARS-CoV-2 infection, thus providing crucial information on a potentially at-risk population, with an efficiency and scale only possible through international collaboration.
C5 Inhibitor Avacincaptad Pegol for Geographic Atrophy Due to Age-Related Macular Degeneration
Authors: Glenn J. Jaffe, Keith Westby, Karl G. Csaky, Jordi Monés, Joel A. Pearlman, Sunil S. Patel, Brian C. Joondeph, John Randolph, Harvey Masonson, Kourous A. Rezaei
Journal: Ophthalmology (2020)

<h3>Purpose</h3> The complement pathway may play a key role in the pathogenesis of age-related macular degeneration (AMD). The safety and efficacy of avacincaptad pegol (Zimura, IVERIC bio Inc, New York, NY), a C5 inhibitor, were assessed in participants with geographic atrophy (GA) secondary to AMD (GATHER1 Study). <h3>Design</h3> International, prospective, randomized, double-masked, sham-controlled, pivotal phase 2/3 clinical trial. <h3>Participants</h3> A total of 286 participants with GA secondary to AMD. <h3>Main Outcome Measures</h3> The primary efficacy endpoint was the mean rate of change in GA over 12 months measured by fundus autofluorescence (FAF) at 3 timepoints: baseline, month 6, and month 12. <h3>Results</h3> The reduction in the mean rate of GA growth (square root transformation) over 12 months was 27.4% (<i>P</i> = 0.0072) for the avacincaptad pegol 2 mg cohort and 27.8% (<i>P</i> = 0.0051) for the avacincaptad pegol 4 mg cohort compared with their corresponding sham cohorts. The results for both dose groups were statistically significant. Avacincaptad pegol was generally well tolerated after monthly administration over 12 months. There were no avacincaptad pegol–related adverse events (AEs) or inflammation. Further, there were no ocular serious AEs (SAEs) and no cases of endophthalmitis. The most frequent ocular AEs were related to the injection procedure. <h3>Conclusions</h3> Intravitreal administration of avacincaptad pegol 2 mg and 4 mg led to a significant reduction of GA growth in eyes with AMD over a 12-month period. Because C5 inhibition theoretically preserves C3 activity, it may offer additional safety advantages. A second confirmatory pivotal clinical trial is underway to confirm the efficacy and safety of avacincaptad pegol in slowing the GA growth (GATHER2 Study).
miRNA-Based Therapies in B Cell Non-Hodgkin Lymphoma
Authors: Teresa Fuertes, Almudena R. Ramiro, Virginia G. de Yebenes
Journal: Trends in Immunology (2020)

Non-Hodgkin lymphoma (NHL) is a diverse class of hematological cancers, many of which arise from germinal center (GC)-experienced B cells. Thus GCs, the sites of antibody affinity maturation triggered during immune responses, also provide an environment that facilitates B cell oncogenic transformation. miRNAs provide attractive and mechanistically different strategies to treat these malignancies based on their potential for simultaneous modulation of multiple targets. Here, we discuss the scientific rationale for miRNA-based therapeutics in B cell neoplasias and review recent advances that may help establish a basis for novel candidate miRNA-based therapies for B cell-NHL (B-NHL).
SAT0725-HPR A DISEASE MANAGEMENT MODEL TYPE CENTER OF ESCELLENCE IN SPONDYLOARTHRITIS – FIRST PILOT ANALYSIS RESULTS
Authors: Anggie Aza, Fernando Rodriguez, Pedro Santos-Moreno, Diana Buitrago-Garcia
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Ankylosing spondylitis (AS) mainly affects the spine and the sacroiliac joints, it is a chronic inflammatory disease that might be associated with a variety of extra spinal lesions involving the eyes, bowel, and skin. In Colombia little is known in regards of this condition. Spondyloarthritis (SpA) is one the most prevalent musculoskeletal disease in the Americas, with an estimated prevalence of 0.5%. This group of patients present a number of unmet needs for accessibility to the consultation, diagnosis and adequate treatments. That for this reason it is necessary to develop a program of Centers of Excellence (CoE) in this pathology, which allows answer to these needs and at the same time to add values for our health systems. <h3>Objectives:</h3> To describe the characteristics of patients with AS who attend to a specialized in SpA disease management model center. <h3>Methods:</h3> We implemented a pilot SpA program under the scheme of CoE, as they are already delineated in projects like REAL-PANLAR for rheumatoid arthritis. We performed a cross sectional study and reviewed the medical charts of patients with AS. All patients had a confirmed diagnosis of AS. We collected demographic data (age, sex, smoking, alcohol consumption); BASDAI, BASFI, DAS, disease specific data treatment with csDMARDs or bDMARDs and comorbidities, evaluation period covered January to December 2018. <h3>Results:</h3> During 2018 257 patients with AS entered to our program. 64% were men and 36% were female; mean age was 48 years ±14. 28% of our patients with SA had comorbidities the most common was high blood pressure 19% followed by diabetes mellitus 4%. Regarding behavioral habits 23% were current smokers and 11% reported to consume alcohol. When we evaluated clinical outcomes BASDAI mean score was 2.95 ± 2.06, BASFI mean score was 3.49 ± 2.36 and, ASDAS mean score was 1.70 ± 1.01. 60% of patients received biological DMARDs and 25% received conventional DMARDs. The remaining 15% received corticoids or pain medications. <h3>Conclusion:</h3> Due to the need to develop CESPAs, in order to define treatment targets type T2T-SpA, we implemented an innovative program in a low-income country with the aim to improve clinical outcomes and avoid so much disability and health economic costs. This descriptive data is the starting point to collect evidence and demonstrate the impact of the program <h3> Disclosure of Interests:</h3> Anggie Aza: None declared, Fernando Rodriguez: None declared, Pedro Santos-Moreno Grant/research support from: Dr Santos has received research grants from Janssen, Abbvie and UCB, Speakers bureau: Dr Santos has received speaker fees from Sanofi, Lilly, Bristol, Pfizer, Abbvie, Janssen and UCB, Diana Buitrago-Garcia: None declared
63 10 year follow-up study of the long term effects of ANTI-TNF therapyon bone metabolism in a cohort of ANTI-TNF naïve IBD patients
Authors: N O’Morain, G Farrell, R Stack, M Hussey, Y Bailey, C Kiat, S Veerappan, D McNamara, A O’Connor, N Breslin, C O’Morain, BM Ryan
Journal: Gut (2017)

Background  Anti-TNF therapy (ATT) has been shown to have beneficial effects on bone metabolism in the short term, but there is a dearth of long term prospective data.  Aim  To evaluate the long term effects of ATT on bone metabolism.  Method  Retrospective observational cohort study of ATT naive IBD patients first evaluated in 2007 by DXA scan and by metabolic bone markers prior to, and one year post commencement of ATT. Patients were invited to undergo repeat DXA scan and serum bone marker measurement.  Results  To date, 73% (n=38/52) patients from the original study have been recruited for 10 year follow up. There were 3 deaths, 4 refusals, 7 uncontactable. DXA scans and serum samples have been collected on 24/38 patients. 50% were female, mean age of 44.5 years (range 27-80). 67% (n=16) Crohn’s, 33% (n=8) UC. 6 patients continued with immunomodulator (IMM), 11 with ATT (Adalimumab (n=5), Infliximab (n=6)), 2 with combination therapy (ATT/IMM), 1 with 5-ASA, 4 no treatment.  Mean T score prior to ATT in 2007 was −1.46 (SD +/-1.24), and 0.81 (SD +/-1.04) at 10 years. The baseline and 10 year mean T-scores were −1.53 (SD +/-1.26) and −0.70 (SD +/-1.13) for patients remaining on ATT and −0.97 (SD +/-1.27) and −0.66 (SD +/-1.01) for those off ATT. Serum analyses are in process.  Conclusions  In this ongoing 10 year follow up study, results suggest that long term (>10 years) treatment with anti-TNF therapy has a beneficial effect on bone metabolism.