tbuckley/cabot-search huggingface dataset:
Abstract B46: Trends in stage at diagnosis for ovarian, fallopian tube, and serous primary peritoneal cancers, 2004–2015
Authors: Julie S. Townsend, Mary C. Puckett, Sherri L. Stewart
Journal: Clinical Cancer Research (2020)

Abstract Introduction: Timely diagnosis is key to reducing distant stage ovarian cancer. The purpose of this study was to examine trends in the proportion of women diagnosed with ovarian cancer by stage and predictors of distant stage diagnosis, comparing two time periods: 2004–2009 and 2010–2015. Methods: We analyzed newly diagnosed malignant ovarian, fallopian tube, and serous primary peritoneal cancers reported to population-based central cancer registries funded by CDC’s National Program of Cancer Registries (NPCR) or the NCI’s Surveillance, Epidemiology, and End Results Program (SEER). We conducted a descriptive analysis examining demographic and clinical characteristics by SEER summary stage at diagnosis (localized, regional, distant, unstaged). We compared women diagnosed between 2004–2009 and 2010–2015 by stage, histology, race/ethnicity, and stage. We built a logistic regression model to examine predictors of a distant stage diagnosis. Results: In 2004, 18% of women were diagnosed at regional stage, which increased to 23% in 2015. There was a slight increase in local stage tumors (14% to 15%). Unstaged tumors declined from 10% to 7% over the same time period, and distant stage tumors declined from 58% to 56%. Only American Indian/Alaska Native (AI/AN) women did not experience a statistically significant decline in distant stage tumors over the two time periods. A greater proportion of serous tumors were diagnosed in the 2010–2015 time period compared to the first (53.2% vs. 50.5%). Predictors of distant stage diagnosis included being diagnosed between 2004–2009, older age (those over age 65), residence in the southern and western U.S., black race, serous histology, and residence in high-poverty census tracts. Conclusion: In the 2010–2015 time period, a smaller proportion of ovarian cancers were distant or unstaged at diagnosis compared to 2004–2009, and most subpopulations of women experienced a decline in distant ovarian cancer. More efforts are needed to increase timely diagnosis and access to specialized care in the southern and western US, high-poverty areas, and among black women. Citation Format: Julie S. Townsend, Mary C. Puckett, Sherri L. Stewart. Trends in stage at diagnosis for ovarian, fallopian tube, and serous primary peritoneal cancers, 2004–2015 [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B46.
Abstract 5574: <i>In vivo</i> model development for immune cell-based therapeutics
Authors: Elizabeth McMichael, Utsav Jetley, Christopher Rudulier, Minasri Borah, Nicole Ganci, Vandhana Ragothaman, Ishina Balwani, Amanda Frain, Priya Pajanirassa, Yuko Miki, Jeffrey Jones, Troy Luster, Marie Keenan, Terina Martinez, Yong Zhang, Birgit Schultes
Journal: Cancer Research (2020)

Abstract The implementation of various mouse models is critical to asses safety, efficacy, and short- and long-term persistence of therapeutic modalities, especially for cell-based therapies. To increase our repertoire of viable humanized murine models, we developed two in vivo models by taking advantage of Taconic's immunodeficient mice, one monitoring graft versus host disease (GvHD) and the other addressing human natural killer (NK) cell cytotoxicity. We utilized NOG mice to develop a model of GvHD, by transplanting human PBMCs at varying doses and monitoring mice for changes in body weight over time. We determined a dose of injected PBMCs that allowed for GvHD to occur yet provided a window of opportunity for potential therapies to slow progression. When human natural T regulatory cells (nTregs) were co-injected with PBMCs in NOG mice, there was prolonged survival and a less rapid loss of body weight as compared to PBMCs alone. To create an NK cytotoxicity model, we transplanted human primary NK cells into NOG-hIL15 mice, which are NOG mice that constitutively produce human IL-15. We showed successful engraftment and proliferation of NK cells, with peak engraftment occurring 4-5 weeks post injection, and that these human primary NK cells were able to persist without signs of xenogeneic GvHD. Utilizing K562 tumor cells that express luciferase, we found these engrafted NK cells have fast and potent cytotoxic activity using IVIS imaging, resulting in elimination of tumor cells as compared to non-engrafted mice. Our results collectively suggest that the two in vivo models developed here will be valuable tools for investigating the clinical benefit of immune cell-based therapeutics. Citation Format: Elizabeth McMichael, Utsav Jetley, Christopher Rudulier, Minasri Borah, Nicole Ganci, Vandhana Ragothaman, Ishina Balwani, Amanda Frain, Priya Pajanirassa, Yuko Miki, Jeffrey Jones, Troy Luster, Marie Keenan, Terina Martinez, Yong Zhang, Birgit Schultes. In vivo model development for immune cell-based therapeutics [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 5574.
Abstract 4279: Automated TRB locus haplotype analysis by long-amplicon TCRB chain sequencing for immune-related adverse events biomarker research
Authors: Jennifer Burke, Frances Chan, Jiajie Huang, Marina Sedova, Timothy Looney, Fiona Hyland
Journal: Cancer Research (2020)

Abstract Introduction: Identifying predictive biomarkers for immune related adverse events (irAEs) following checkpoint blockade inhibition (CPI) remains an outstanding goal of immune-oncology translational research. Polymorphism within the T cell receptor variable gene (TRBV) has been proposed as a potential risk factor for irAEs owing to the potential link between TRBV polymorphism and chronic autoimmune disease. Efforts to interrogate the potential biomarker utility of TRBV polymorphism have been hampered by the repetitive nature of the TRB locus. We previously demonstrated a method for inferring TRB locus haplotypes from long amplicon TCRB chain sequencing data, which we used to identify major haplotype groups in a set of 81 Caucasians. Here we present an automated method for haplotype group assignment from TCRB chain sequencing data. Methods: Rearranged TCRB chains from 10 blood samples were amplified and sequenced from 25ng peripheral blood total RNA via the Oncomine™ TCRB-LR assay using the Genexus™ Integrated Sequencer. 12 samples were run per chip with 4 samples run in each lane. TCRB clonotyping and repertoire feature analysis was performed using the Genexus™ software v5.107.14. Automated haplotype group assignment was performed by generation and comparison of TRBV allele profiles to those presented in DOI: 10.4103/JIPO.JIPO_16_19. For context, TCR evenness, convergence, and haplotype group assignment were compared to values obtained following analysis of the same samples via the GeneStudio™ S5 platform and Ion Reporter™ 5.12 software. Results: TCR Evenness and convergence values were highly correlated across replicates run on the Genexus™ Integrated Sequencer (Spearman correlation &amp;gt;0.95 and &amp;gt;.70, respectively). Evenness at equivalent clone count and convergence at equivalent sequencing depth were not significantly different across platforms (Spearman correlation &amp;gt;0.88). Haplotype group assignments demonstrated 100% agreement across replicates on both platforms. Conclusions: We demonstrate an automated and reproducible research method for TRB haplotype group assignment via the Oncomine™ TCR-Beta LR Assay, GX run on the Genexus™ Integrated Sequencer. Future studies will evaluate the potential biomarker utility of TRB haplotyping for the prediction of irAEs. Citation Format: Jennifer Burke, Frances Chan, Jiajie Huang, Marina Sedova, Timothy Looney, Fiona Hyland. Automated TRB locus haplotype analysis by long-amplicon TCRB chain sequencing for immune-related adverse events biomarker research [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 4279.
Timing of Oral P2Y12 Inhibitor Administration in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome
Authors: Giuseppe Tarantini, Marco Mojoli, Ferdinando Varbella, Roberto Caporale, Stefano Rigattieri, Giuseppe Andò, Plinio Cirillo, Simona Pierini, Andrea Santarelli, Paolo Sganzerla, Luisa Cacciavillani, Luciano Babuin, Nicoletta De Cesare, Ugo Limbruno, Alberto Massoni, Andrea Rognoni, Daniela Pavan, Flavia Belloni, Carlo Cernetti, Luca Favero, Francesco Saia, Luca Nai Fovino, Giulia Masiero, Loris Roncon, Valeria Gasparetto, Marco Ferlini, Federico Ronco, Roberta Rossini, Paolo Canova, Daniela Trabattoni, Alessandra Russo, Vincenzo Guiducci, Carlo Penzo, Fabio Tarantino, Ciro Mauro, Elena Corrada, Giovanni Esposito, Alfredo Marchese, Sergio Berti, Matteo Martinato, Danila Azzolina, Dario Gregori, Dominick J. Angiolillo, Giuseppe Musumeci
Journal: Journal of the American College of Cardiology (2020)
Reply
Authors: Karim J. Halazun, Abbas A. Rana, Rachel E. Patzer, Benjamin Samstein, Robert S. Brown, Jean C. Emond
Journal: Hepatology (2014)

Potential conflict of interest: Dr. Brown consults for and received grants from Gilead, AbbVie, Janssen, and Vertex. He consults for Merck, Genentech, and Salix. We thank the authors for their insightful comments. The lack of uniformity in organ allocation among regions has allowed us and others to examine the vast regional variation in waiting times to discover major differences in the outcomes of hepatocellular carcinoma (HCC) patients on the list, both with respect to recurrence and overall outcome.1 It is clear that uniformity among transplant centers in the U.S. and worldwide in both access and treatment of these patients is required, and will allow the transplant community to better understand how to manage patients with HCC on the waiting list. While the Milan criteria are widely accepted despite having no specific tumor biology indices associated with them, many groups including our own have attempted to define markers of poor biology; however, none of these have been universally accepted or applied to organ allocation models.3 Currently, it seems that lack of progression of tumor while waiting for a liver transplant, or successful down‐staging of tumor, may be the best available biological marker, as demonstrated by the UCSF group and our article.1 We agree that the development, and universal implementation of appropriate and reproducible biomarkers of tumor biology to allocation models of liver transplantation for HCC is required in order to optimize outcomes for HCC patients.
Advancing Assessment, Analysis, and Reporting of Safety and Tolerability in Cancer Trials
Authors: Paul G Kluetz, Bellinda L King-Kallimanis, Daniel Suzman, Elaine Chang, Michael M Brave, Chana Weinstock, Vishal Bhatnagar, Julia A Beaver, Meredith K Chuk
Journal: JNCI Journal of the National Cancer Institute (2020)
THU0121 Bcl-xl and plasma cell survival in rheumatoid synovium
Authors: S Busteed, MW Bennett, M Stone, C Molloy, J O’Connell, F Shanahan, MG Molloy
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Bcl-xL is a Bcl-2 homologue that regulates lymphocyte apoptosis. It has been reported that co-culture of B cells with rheumatoid synovial stromal cells induces upregulation of Bcl-xL, consequently inhibiting B cell apoptosis. Impaired apoptosis of auto-antibody producing B cells may contribute to the perpetuation of inflammation in rheumatoid arthritis (RA). The phenotype of synovial T lymphocytes in RA – Bcl-xL<sup>high</sup>/Bcl-2<sup>low</sup>, may also be linked to the enhanced survival of T lymphocytes within the joint. <h3>Objectives</h3> In this study, we examined the expression of Bcl-xL in rheumatoid synovium using immunohistochemistry. <h3>Methods</h3> Sections of synovium were obtained intraoperatively from patients with RA (n = 18). Specimens from patients with osteoarthritis were used as non-inflammatory controls (n = 9). Staining was carried out using a polyclonal rabbit antibody to Bcl-xL. Peripheral blood lymphocytes were used as positive biological controls. Detection of cell death was carried out using the TUNEL assay (terminal deoxynucleotidyl transferase (TdT) mediated dUTP nick end labelling). Identification of plasma cells within the lymphocyte population was performed using a monoclonal antibody to CD138. <h3>Results</h3> Bcl-xL was expressed in both RA and OA tissue. Of note, there was a marked infiltrate of Bcl-xL positive cells in 13 of the 18 RA sections with scattered positive cells in a further 2 sections. Only 1 of the 9 OA sections demonstrated a similar degree of plasma cell infiltration and Bcl-xL expression, although a few positive plasma cells were noted in the remaining sections. Plasma cells infiltrates that were Bcl-xL positive were noted to be TUNEL-negative on consecutive sections. <h3>Conclusion</h3> Upregulation of Bcl-xL by plasma cells in rheumatoid synovium may prevent their elimination by apoptosis and may play a role in the pathogenesis in rheumatoid arthritis.
Abstract 6644: A comprehensive <i>in vitro</i> and <i>in vivo</i> system to evaluate STING agonist efficacy in cancer therapeutics
Authors: Xiaohe Shi, Feifei Fan, Ruicheng Wei, Xiangyang Zuo, Xiutao Lu, Quanhong Sun
Journal: Cancer Research (2020)

Abstract A number of stimulator of interferon genes protein (STING) agonists has recently been developed to treat cancer and infectious diseases. To investigate the binding of ligand to STING and subsequent activation of the STING pathway, we used the protein thermal shift assay, a high-throughput screening method for intermolecular interaction involving a protein of interest, to identify previously unknown compounds that bind to STING. To determine the functional consequence of ligand binding, we constructed IFN-β-Luc THP1 reporter cell line, to evaluate the pathway activation together with IFNβ secretion. In addition, we incubated human peripheral blood mononuclear cells (PBMCs) with STING agonist and measured phosphorylation of STING, phosphorylation of IRF3 and the secretion of cytokines such as IFN-β by ELISA or Luminex. To determine the in vivo therapeutic effects of STING agonists, we performed efficacy studies in syngeneic mouse models of melanoma (B16F10 cell line), colorectal cancer (CT-26 cell line) or breast cancer (4T1 cell line) with intratumoral delivery of test compounds. Test Treatment with STING agonists resulted in significant tumor growth inhibition as measured by tumor volume and significantly improved survival. Tumor-reactive IFN-γ secreting CD8+ T cells were harvested from spleens, purified by immunomagnetic sorting, and immediately used in ELISPOT assays using the mouse IFN-γ ELISPOT Kit. Tumor-infiltrating lymphocytes (TILs) have also been assessed in harvested melanoma (B16F10) tumors. We found that treatment with STING agonists resulted in increased CD69 percentage in CD8+ T cells in TILs, and decreased MHCII levels in macrophages and DCs in TILs. In summary, we have established reporter-based in vitro assays and in vivo efficacy validation platforms, which can be used for STING agonists efficacy evaluation for cancer therapy and combination IO target therapy. Citation Format: Xiaohe Shi, Feifei Fan, Ruicheng Wei, Xiangyang Zuo, Xiutao Lu, Quanhong Sun. A comprehensive in vitro and in vivo system to evaluate STING agonist efficacy in cancer therapeutics [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 6644.
Abstract CT231: Clinical study of the safety and tolerability of laser interstitial thermal therapy and avelumab for recurrent glioblastoma
Authors: Adilia Hormigo, John Mandeli, Saadi Ghatan, Constantinos Hadjipanayis, Raymond Yong, Seunghee Kim-Schulze, Sacha Gnjatic
Journal: Cancer Research (2020)

Abstract Background: Glioblastoma (GBM) is a fatal disease with no standard care for disease progression and as other cancers is known to evade the immune system. Avelumab is a human IgG1 antibody that binds PD-L1 and blocks the interaction between PD-L1 and its receptors PD-1 and B7-1. Consequently, the suppressive effect on T cell function is inhibited and anti-tumor CD8+ T cells cytotoxicity is restored.Laser Interstitial Thermal Therapy (LITT) is a minimally invasive technique that allows the delivery of light energy causing disruption of the blood-brain barrier and hyperthermia of a brain lesion, initiating a cascade of events leading to coagulative necrosis and potentially triggering immunogenic death of cancer cells. It is hypothesized that avelumab combined with MRI-guided LITT has acceptable safety, tolerability and will generate robust immunomodulation and clinical activity to treat brain cancer. Methods: This phase 1 study is enrolling adult patients with first recurrence of GBM. The study follows a 3+3 design exploring safety and tolerability in part A, Avelumab alone and part B, Avelumab combined with LITT (NCT03341806). Objective response will be determined by iRANO criteria and secondary objectives include PFS and OS. Avelumab is administered intravenously within a week of LITT and every two weeks thereafter until disease progression or intolerable toxicity. Tissue immune biomarkers, signature of plasma analytes, and circulating cellular signature profiling are assessed. Part A and B completed enrollment with no serious infusion or immune-related adverse events. The study will proceed with an expansion cohort on January 2020. A Simon minimax two-stage design will be used for efficacy. The first stage consists of the 6 subjects evaluable from the safety cohorts in Part 1B together with the first 8 subjects in the expansion cohort (total of 14 subjects). Citation Format: Adilia Hormigo, John Mandeli, Saadi Ghatan, Constantinos Hadjipanayis, Raymond Yong, Seunghee Kim-Schulze, Sacha Gnjatic. Clinical study of the safety and tolerability of laser interstitial thermal therapy and avelumab for recurrent glioblastoma [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 CT231.
Induced pluripotent stem cells-derived microvesicles accelerate deep second-degree burn wound healing in mice through miR-16-5p-mediated promotion of keratinocytes migration
Authors: Yuan Yan, Ruijun Wu, Yunyao Bo, Min Zhang, Yinghua Chen, Xueer Wang, Mianbo Huang, Baiting Liu, Lin Zhang
Journal: Theranostics (2020)

Background: Induced pluripotent stem cells (iPSCs) have emerged as a promising treatment paradigm for skin wounds. Extracellular vesicles are now recognized as key mediators of beneficial stem cells paracrine effects. In this study, we investigated the effect of iPSCs-derived microvesicles (iPSCs-MVs) on deep second-degree burn wound healing and explored the underlying mechanism. Methods: iPSCs-MVs were isolated and purified from conditioned medium of iPSCs and confirmed by electron micrograph and size distribution. In deep second-degree burn model, iPSCs-MVs were injected subcutaneously around wound sites and the efficacy was assessed by measuring wound closure areas, histological examination and immunohistochemistry staining. In vitro, CCK-8, EdU staining and scratch assays were used to assess the effects of iPSCs-MVs on proliferation and migration of keratinocytes. Next, we explored the underlying mechanisms by high-throughput microRNA sequencing. The roles of the miR-16-5p in regulation of keratinocytes function induced by iPSCs-MVs were assessed. Moreover, the target gene which mediated the biological effects of miR-16-5p in keratinocytes was also been detected. Finally, we examined the effect of local miR-16-5p treatment on deep second degree-burns wound healing in mice. Results: The local transplantation of iPSCs-MVs into the burn wound bed resulted in accelerated wound closure including the increased re-epithelialization. In vitro, iPSCs-MVs could promote the migration of keratinocytes. We also found that miR-16-5p is a critical factor in iPSCs-MVs-induced promotion of keratinocytes migration in vitro through activating p38/MARK pathway by targeting Desmoglein 3 (Dsg3). Finally, we confirmed that local miR-16-5p treatment could boost re-epithelialization during burn wound healing. Conclusion: Therefore, our results indicate that iPSCs-MVs-derived miR-16-5p may be a novel therapeutic approach for deep second-degree burn wound healing.
FRI0071 Responses to infliximab therapy in the attract trial assess with the disease activity score (das): clinical response measured by das at 102 weeks correlates with arrest of radiologic progression and shows higher response rate than acr20 criteria
Authors: CE Antoni, A Kavanaugh, B Manger, G Keenan, T Schaible, G Harriman, K Patel, J Kalden
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> In the ATTRACT trial, the anti-TNF-monoclonal antibody infliximab showed significant improvement in disease activity score (DAS), reduction in signs and symptoms, inhibition of progression of structural damage and improved quality of life in rheumatoid arthritis (RA) patients, at 54 weeks. Inhibition of radiologic progression by infliximab occurred in both ACR20 responders and non-responders. This suggests that the ACR20 criteria might underestimate clinical responses to therapeutic agents. <h3>Objectives</h3> To examine effect of infliximab on DAS RA patients after two years of treatment. <h3>Methods</h3> DAS was calculated as follows: 0.56*SQRT(TJC) + 0.28*SQRT(SJC) +0.7ln (ESR) + 0.014*(pt global (VAS)). DAS responses were characterised as ?None?, ?Moderate? or ?Good? using DAS scores at 102 week and change in DAS from baseline to 102 week. Patients with ?Good? or ?Moderate? response were considered DAS responders. Fisher?s exact test was used to compare proportion of patients with DAS response by treatment group. <h3>Results</h3> Clinical responses as measured by ACR20 and DAS correlated with each other; however, overall the response rate was higher with the DAS. At week 102, 84% of patients achieving ACR20 response were also responders using DAS; 45% of ACR20 non-responders were DAS responders. The DAS showed a statistically significant difference for each infliximab treatment group vs placebo (p &lt; 0.001). ACR20 and DAS response rate at Wk 102 are presented below, by treatment group. <h3>Conclusion</h3> Responses assessed with ACR20 and DAS have previously been shown to correlate. Analysis of data from the ATTRACT trial suggests that the DAS may be more sensitive to clinical improvement. The improved sensitivity of DAS, and the fact that it evaluates both change in response to therapy and also extent of residual disease activity, support its routine use as an endpoint in clinical trials.