tbuckley/cabot-search huggingface dataset:
Abstract 5000: Epigenomic profiling of oral cancer
Authors: Sayaka Yoshiba
Journal: Cancer Research (2012)

Abstract Epigenetic aberration, such as dysregulation of DNA mathylation is often associated with human carcinogenesis. To analyze DNA methylation profiles of oral cancers, and to identify the methylation pattern specific to the clinicopathological features, we performed genome-wide methylation analysis using Infinium HumanMethylation27 BeadArray system. We found 2,361 aberrantly methylated CpG sites in 59 oral cancers compared to 3 normal mucosal tissues. By unsupervised clustering analysis, oral cancer was divided into two methylation epigenotypes that are significantly correlated with incidence of lymph node metastasis and differentiation grades. We selected the classifier genes that can predict tumor metastasis in the training set, and demonstrated that they are validated to be predictive in the independent test sample, preoperative biopsy samples. In summary, we identified two methylation epigenotypes correlated with clinical outcome in oral cancer, and candidate classifier genes that would be useful in patient stratification for intensive therapy to overcome the tumor recurrence. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5000. doi:1538-7445.AM2012-5000
Abstract 1872: Development of reference reagents to accelerate research on the RAS pathway
Authors: Dominic Esposito, Jennifer Mehalko, Vanessa Wall, Carissa Grose, William Gillette, Robert Stephens
Journal: Cancer Research (2016)

Abstract The RAS Reference Reagents program within the NCI RAS Initiative is produces and distributes qualified DNA vectors, cell lines, and viruses to the external community to facilitate research into RAS biology and development of RAS cancer therapeutics. DNA vectors representing a variety of RAS mutations, as well as a complete collection of 180 genes in the RAS pathway are available as Gateway-compatible Entry clones. These clones represent the most commonly expressed transcript forms of the 180 genes, many of which were not previously available in full-length, wildtype forms. The vectors can be used with the FNLCR combinatorial cloning library to easily generate a large number of different types of expression clones with various promoters, fusion tags, and plasmid backbones. Additional reagents under construction include validated plasmid and lentiviral reagents for shRNA and CRISPR delivery, qualified cell lines for use in research into the RAS pathway, and systems for the generation of highly purified and characterized Ras and Ras-related proteins. A highlight of these reagents are materials for the high yield production of properly processed, prenylated KRAS protein using an engineered insect cell expression system. This system could be used to produce other prenylated small GTPases at levels not previously attainable. All of the resources of the RAS Reference Reagents program are readily available to the academic community through simple mechanisms, and can be licensed to industry scientists as well. The program is also interested in identifying the needs of the community for additional RAS-related resources, and is developing methods for vetting requests from the outside to provide additional reagents. Citation Format: Dominic Esposito, Jennifer Mehalko, Vanessa Wall, Carissa Grose, William Gillette, Robert Stephens. Development of reference reagents to accelerate research on the RAS pathway. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1872.
Prophylactic Intervention with N-Acetyl-L-Cysteine before Allotransplant Could Reduce the Occurrence of Poor Hematopoietic Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Yuan Kong, Yu Wang, Yuan-Yuan Zhang, Min-Min Shi, Xiao-Dong Mo, Yu-Qian Sun, Ying-Jun Chang, Lan-Ping Xu, Xiaohui Zhang, Kaiyan Liu, Xiao-Jun Huang
Journal: Blood (2018)
P158/O07 Pathological inflammation in experimental spondyloarthritis is characterized by high endothelial venules and ectopic lymphoid structures in the bone marrow
Authors: MH Kaaij, JP van Hamburg, J Rip, G Kollias, DL Baeten, M Nolte, LM van Duivenvoorde, SW Tas
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Student for a master or a PhD. <h3>Introduction</h3> Tumour necrosis factor (TNF) is important in immune-mediated inflammatory diseases such as spondyloarthritis (SpA). Transmembrane (tm)TNF-transgenic (tg) mice<sup>1</sup> that overexpress tmTNF develop SpA symptoms, including inflammation, ectopic lymphoid structures (ELS) in bone marrow (BM), bone destruction and bone formation. SpA patients have extensive angiogenesis in inflammatory and bone forming regions. <h3>Objectives</h3> To investigate whether there is a link between pathological angiogenesis and ELS in tmTNF tg mice in the BM. <h3>Methods</h3> Ankles, femora, tibiae, vertebrae and spleens from 6 and 12 weeks and 8 months old tmTNF tg mice and wild-type (WT) littermates (n=5 per age per group) were dissected and analyzed with confocal microscopy and analyzed 12 week old tmTNF tg and WT mice (n=4) with flow cytometry. To study the importance of TNF-R signaling, tmTNF tg mice lacking TNF-RI (tmTNF tgxTNF-RI<sup>-/-</sup>) or TNF-RII (tmTNF tgxTNF-RII<sup>-/-</sup>) (n=4 per group) were used. <h3>Results</h3> Immunofluorescent evaluation demonstrated that BM of tmTNF tg mice contained significantly more and extensive ELS. These ELS are limited to BM of the vertebrae and ankles, and are in close proximity of MECA79<sup>+</sup>high endothelial venules (HEVs). ELS predominantly consisted of B220<sup>+</sup> B cells, of which most are IgD<sup>+</sup> naive B cells. Preliminary flow cytometric analysis revealed a trend towards an increase in IgD-CD95<sup>+</sup> germinal center B cells and CXCR5<sup>+</sup>PD-1<sup>+</sup>FoxP3<sup>-</sup>CTLA4<sup>-</sup> T follicular helper cells and CXCR5<sup>+</sup>PD-1<sup>+</sup>FoxP3<sup>+</sup>CTLA4<sup>+</sup> in the vertebrae of tmTNF tg mice compared to WT littermates. Meanwhile, B cell lineages in the BM of tmTNF tg hind limbs were not altered. Furthermore, preliminary data indicates that BM and spleen from tmTNF tg mice contain more IgA<sup>+</sup> plasma cells compared to WT littermates. tmTNF tgxTNF-RI<sup>-/-</sup> mice did not display lymphoid aggregates or HEVs in the BM, while tmTNF tgxTNF-RII<sup>-/-</sup> mice did, although to a lesser extent than tmTNF tg mice. <h3>Conclusions</h3> tmTNF overexpression in mice results in extensive ELS associated with HEVs in the BM, which is likely to be mediated through TNF-RI signaling. HEV formation may lead to persistence of inflammation in the BM which contributes to pathology. <h3>Reference</h3> Alexopoulou L, <i>et al. Eur J Immunol</i> 1997;27(10):2588–92 <h3>Disclosure of Interest</h3> None declared
Genetic and Environmental Determinants of Immune Response to Cutaneous Melanoma
Authors: Joanna Poźniak, Jérémie Nsengimana, Jonathan P. Laye, Sally J. O’Shea, Joey Mark S. Diaz, Alastair P. Droop, Anastasia Filia, Mark Harland, John R. Davies, Tracey Mell, Juliette A. Randerson-Moor, Sathya Muralidhar, Sabrina A. Hogan, Sandra Nicole Freiberger, Mitchell P. Levesque, Graham P. Cook, D. Timothy Bishop, Julia Newton-Bishop
Journal: Cancer Research (2019)

Abstract The immune response to melanoma improves the survival in untreated patients and predicts the response to immune checkpoint blockade. Here, we report genetic and environmental predictors of the immune response in a large primary cutaneous melanoma cohort. Bioinformatic analysis of 703 tumor transcriptomes was used to infer immune cell infiltration and to categorize tumors into immune subgroups, which were then investigated for association with biological pathways, clinicopathologic factors, and copy number alterations. Three subgroups, with “low”, “intermediate”, and “high” immune signals, were identified in primary tumors and replicated in metastatic tumors. Genes in the low subgroup were enriched for cell-cycle and metabolic pathways, whereas genes in the high subgroup were enriched for IFN and NF-κB signaling. We identified high MYC expression partially driven by amplification, HLA-B downregulation, and deletion of IFNγ and NF-κB pathway genes as the regulators of immune suppression. Furthermore, we showed that cigarette smoking, a globally detrimental environmental factor, modulates immunity, reducing the survival primarily in patients with a strong immune response. Together, these analyses identify a set of factors that can be easily assessed that may serve as predictors of response to immunotherapy in patients with melanoma. Significance: These findings identify novel genetic and environmental modulators of the immune response against primary cutaneous melanoma and predict their impact on patient survival. See related commentary by Anichini, p. 2457
Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet
Authors: Miguel A. Sanz, Pierre Fenaux, Martin S. Tallman, Elihu H. Estey, Bob Löwenberg, Tomoki Naoe, Eva Lengfelder, Hartmut Döhner, Alan K. Burnett, Sai-Juan Chen, Vikram Mathews, Harry Iland, Eduardo Rego, Hagop Kantarjian, Lionel Adès, Giuseppe Avvisati, Pau Montesinos, Uwe Platzbecker, Farhad Ravandi, Nigel H. Russell, Francesco Lo-Coco
Journal: Blood (2019)
217. Development of an Effective Cancer Vaccine Platform Using Attenuated Salmonella to Deliver Recombinant Tumor-Associated Antigens
Authors: Xin Xu, Suhrab Kurbanov, Linjie Guo, Xiuhua Gao, James E. Galen, Leonid S. Metelitsa
Journal: Molecular Therapy (2015)

Inadequate antigen delivery is one of the major limitations of modern cancer vaccine vectors. To overcome this challenge, we exploited Salmonella Pathogenicity Island 2 (SPI2) and its type III secretion system (T3SS) to deliver a tumor-associated antigen (TAA) of choice into the cytosol of antigen-presenting cells (APC) in situ. In a recent report, we demonstrated that an attenuated strain of S. typhimurium, MvP728, which was engineered to express SPI2-regulated oncoprotein survivin, induced potent CD8 T-cell-mediated antitumor response that was curative in a murine model of highly aggressive lymphoma. In further development of this technology for clinical use, the vaccine has been transferred from an experimental strain of S. typhimurium to a clinically validated strain of S. typhi, CVD908. To adapt CVD908 to stably express recombinant antigens without antibiotic-dependent selection, we used a recently reported plasmid stabilization system that encodes the single-stranded binding protein (SSB), an essential protein in DNA metabolism, which was deleted from the bacterial chromosome. The SPI2-regulated expression cassette was then cloned into the SSB plasmid, so that the resultant construct maintained bacterial vector stability while expressing and translocating TAAs. We found that CVD908Dssb vector effectively infects human dendritic cells in vitro and translocates recombinant human survivin and MYCN oncoproteins into their cytosol. Furthermore, CVD908Dssb remains stable and immunogenic in mice, providing further support for choosing this strain as a basis for an effective cancer vaccine platform.
89Zr-labeled anti-PD-L1 CX-072 PET imaging in human xenograft and syngeneic tumors
Authors: D. Giesen, L.N. Broer, M.N. Lub-De Hooge, I. Popova, B. Howng, O. Vasiljeva, E.G.E. de Vries, M. Pool
Journal: Annals of Oncology (2019)

Background: Immune checkpoint inhibiting antibodies have antitumor activity across several tumor types, but can also elicit immune-mediated adverse events (imAEs). CX-072 is an investigational antibody prodrug (Probody™ therapeutic), reactive to the murine and human programmed death-ligand 1 (PD-L1) immune checkpoint. CX-072 can be activated to a fully avid antibody by tumor-associated proteases that remove the masking peptides blocking the antigen-binding domain, which may limit peripheral PD-L1 binding and therefore imAEs. CX-072 was radiolabeled with zirconium-89 (89Zr) to study its biodistribution and tumor- versus lymphoid tissue-targeting properties using positron emission tomography (PET). Methods: CX-072, non-specific Probody™ therapeutic control (PbCtrl) and CX-072 parental antibody (CX-075) were radiolabeled with 89Zr. Human PD-L1-expressing MDA-MB-231 tumor-bearing BALB/c nude mice received 10 μg 89Zr-CX-072, 89Zr-PbCtrl or 89Zr-CX-075 (∼5 MBq) supplemented with 0, 40 or 240 µg of respective unlabeled antibody. Biodistribution was also evaluated in C57BL6/J mice bearing PD-L1-expressing MC38 syngeneic colon adenoma tumors. Mice underwent PET scans 1, 3 and 6 days post intravenous injection (pi), followed by ex vivo analysis. Results: In MDA-MB-231 tumors, 89Zr-CX-072 and 89Zr-CX-075 showed comparable uptake of 8.7 ± 1.0%ID/g and 8.8 ± 2.9%ID/g respectively for the 10 µg total protein dose, which is 2.3-fold higher compared to 89Zr-PbCtrl. Autoradiography showed 89Zr-CX-072 localization in PD-L1-positive tumor tissue areas on immunohistochemistry. Activated CX-072 was detected by capillary electrophoresis immunoassay mainly in MDA-MB-231 tumor, with limited amounts found in spleen. Flow cytometry confirmed PD-L1 expression in lymphoid tissues of C57BL6/J mice, while 89Zr-CX-072 uptake in these tissues was similar to 89Zr-PbCtrl and significantly lower compared to 89Zr-CX-075. Conclusions:89Zr-CX-072 accumulates in PD-L1-expressing tumors with minor uptake in murine peripheral lymphoid tissues, confirming that the CX-072 structure limits uptake in non-tumor, PD-L1-expressing tissues. We developed clinical grade 89Zr-CX-072 to study its whole-body distribution in patients. Legal entity responsible for the study: Dept. of Medical Oncology, University Medical Center Groningen (UMCG), The Netherlands. Funding: CytomX Therapeutics Inc. Disclosure: I. Popova, B. Howng, O. Vasiljeva: Employee: CytomX Therapeutics Inc. E.G.E. de Vries: Research funding: CytomX was made available to her institution (UMCG); Advisory boards: Pfizer, Daiichi Sankyo; Other funding: Amgen, Bayer, Chugai, G1 Therapeutics, Genentech/Roche, Nordic Nanovector, Regeneron, Synthon, all payments to UMCG. All other authors have declared no conflicts of interest.
P042/O05 Molecular mimicry and autoimmunity: anti-P.gingivalis antibody response in ACPA-positive rheumatoid arthritis
Authors: N Sherina, N Sippl, L Israelsson, E Le Maitre, N Kharlamova, M Hansson, K Eriksson, T Yucel-Lindberg, V Malmström, K Amara, K Lundberg
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Student for a master or a PhD. <h3>Introduction</h3> The presence of anti-citrullinated protein antibodies (ACPAs) is a hallmark of rheumatoid arthritis (RA). ACPAs specifically recognize citrullinated epitopes, a result of a post-translational modification catalyzed by peptidyl arginine deiminases (PAD). Based on the unique feature of the periodontal bacteria <i>Porphyromonas gingivalis</i> (<i>P.gingivalis</i>) to express <i>P</i>.PAD it has been suggested that ACPA-positive RA may be precipitated in the gum mucosa. <h3>Objectives</h3> To address this hypothesis our aims were to investigate the antibody response against a citrullinated <i>P.</i>PAD peptide (CPP3) in patients with RA, chronic periodontitis (PD) and in controls. In addition, we generated monoclonal antibodies (mAbs) from gingival tissue B cells of RA patient aiming to investigate whether citrulline-specific B cells may reside in the gingiva. <h3>Methods</h3> Gingival tissue-derived single CD19+ B cells from an ACPA-positive RA patient with PD were sorted by flow cytometry. Immunoglobulin variable region genes were sequenced and expressed to generate recombinant mAbs. CPP3-reactivity was analysed by ELISA in serum samples from 66 PD patients, 63 periodontally healthy controls (non-PD), 200 RA patients, and 120 non-RA controls, as well as in 55 mAbs. Differences in antibody levels were examined using Mann-Whitney <i>U</i> test for independent groups. <h3>Results</h3> Anti-CPP3 antibody levels were low in non-PD controls, while 65% of PD patients showed elevated levels (p&lt;0.0001). Significantly increased antibody levels were also detected in 50% of ACPA-positive RA, 20% of ACPA-negative RA, and in 37% of non-RA controls (p&lt;0.0001). Notably, this antibody response was citrulline-specific, as the antibody response against the arginine-containing control peptide RPP3 was significantly lower in all subsets (p&lt;0.0001). Among 55 mAbs from gingival tissue, 14 (25%) unique clones were CPP3-reactive, of which 4 showed cross-reactivity with RPP3. Interestingly, 4 out of 14 (29%) CPP3-reactive clones also bound citrullinated peptides derived from human a-enolase, filaggrin and histone 4, demonstrating cross-reactivity between a bacterial epitope and human epitopes on a monoclonal level. <h3>Conclusions</h3> This study shows that a substantial proportion of systemically healthy individuals possess ACPAs directed against <i>P.gingivalis</i>, and these ACPAs also bind epitopes on human proteins. Based on our data, we propose that the ACPA response may be triggered by <i>P.gingivalis</i> via an antibody response against CPP3, which cross-reacts with human citrullinated proteins by mechanisms of molecular mimicry. <h3>Disclosure of Interest</h3> None declared.
Cancer screening in the United States, 2017: A review of current American Cancer Society guidelines and current issues in cancer screening
Authors: Robert A. Smith, Kimberly S. Andrews, Durado Brooks, Stacey A. Fedewa, Deana Manassaram‐Baptiste, Debbie Saslow, Otis W. Brawley, Richard C. Wender
Journal: CA A Cancer Journal for Clinicians (2017)

Answer questions and earn CME/CNE Each year, the American Cancer Society publishes a summary of its guidelines for early cancer detection, data and trends in cancer screening rates, and select issues related to cancer screening. In this issue of the journal, the authors summarize current American Cancer Society cancer screening guidelines, describe an update of their guideline for using human papillomavirus vaccination for cancer prevention, describe updates in US Preventive Services Task Force recommendations for breast and colorectal cancer screening, discuss interim findings from the UK Collaborative Trial on Ovarian Cancer Screening, and provide the latest data on utilization of cancer screening from the National Health Interview Survey. CA Cancer J Clin 2017;67:100-121. © 2017 American Cancer Society.
Non-Hodgkin’s Lymphomas, Version 2.2014
Authors: Andrew D. Zelenetz, Leo I. Gordon, William G. Wierda, Jeremy S. Abramson, Ranjana H. Advani, C. Babis Andreadis, Nancy Bartlett, Naresh Bellam, John C. Byrd, Myron S. Czuczman, Luis E. Fayad, Richard I. Fisher, Martha J. Glenn, Nancy Lee Harris, Richard T. Hoppe, Steven M. Horwitz, Christopher R. Kelsey, Youn H. Kim, Susan Krivacic, Ann S. LaCasce, Auayporn Nademanee, Pierluigi Porcu, Oliver Press, Rachel Rabinovitch, Nishitha Reddy, Erin Reid, Lubomir Sokol, Lode J. Swinnen, Christina Tsien, Julie M. Vose, Joachim Yahalom, Nadeem Zafar, Mary Dwyer, Hema Sundar
Journal: Journal of the National Comprehensive Cancer Network (2014)

Non-Hodgkin's lymphomas (NHLs) are a heterogeneous group of lymphoproliferative disorders originating in B lymphocytes, T lymphocytes, or natural killer cells. Follicular lymphoma (FL) is the most common subtype of indolent NHL, accounting for approximately 22% of all newly diagnosed cases of NHL. The incorporation of rituximab to chemotherapy regimens has become a widely accepted standard of care for first-line therapy for patients with FL. Maintenance and consolidation therapy with rituximab and radioimmunotherapy have also been associated with improved progression-free survival in patients experiencing response to first-line therapy. Despite therapeutic advances that have improved outcomes, FL is generally considered a chronic disease characterized by multiple recurrences with current therapies. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with FL.
P024 Disturbed sexual functioning in female patients with idiopathic inflammatory myopathies
Authors: B Hermankova, M Spiritovic, H Smucrova, S Oreska, H Storkanova, K Pavelka, L Senolt, H Mann, J Vencovsky, M Tomcik
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Student for a master or a PhD. <h3>Introduction</h3> Idiopathic inflammatory myopathies (IIM) are characterized by inflammation and atrophy of skeletal muscles, pulmonary and articular involvement, which leads to functional impairment, reduced quality of life including sexual life. <h3>Objectives</h3> The aim of this study was to assess sexual functions/quality of life and pelvic floor function in female IIM patients compared to age-/sex-matched healthy controls (HC). <h3>Methods</h3> In total, 22 women with IIM [mean age: 55.1, disease duration: 7.9 years, dermatomyositis (DM, 8)/polymyositis (PM, 10)/necrotizing myopathy (IMNM, 3)/inclusion body myositis (IBM, 1)], who fulfilled the Bohan/Peter 1975 criteria for DM/PM, and 22 healthy controls (mean age: 55.1 years) filled in 12 well-established and validated questionnaires assessing sexual function and pelvic floor function, fatigue, physical activity and depression. We used the following questionnaires: Female Sexual Function Index (FSFI), Brief Index of Sexual Function for Women (BISF-W), Sexual Quality of Life Questionnaire (SQoL-F), Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), Pelvic Floor Distress Inventory Questionnaire (PFIQ7), Fatigue Impact Scale (FIS), Beck's Depression Inventory II (BDI II), Health Assessment Questionnaire (HAQ) and Human Activity Profile (HAP). <h3>Results</h3> Compared to HC, patients with IIM had significantly higher prevalence and greater severity of sexual dysfunction (FSFI, BISF-W: in all subscales as well as total scores), dysfunction of pelvic floor (PISQ-12), and worse sexual quality of life (SQoL-F). Worse scores in IIM patients were associated with elevated muscle enzyme levels [lactate dehydrogenase: FSFI (r=−0.524, p=0.0123), BISFW (r=−0.528, p=0.0115)], greater fatigue [FIS: FSFI (r=−0.434, p=0.0438), BISF-W (r=−0.488, p=0.0211), SQoL-F (r=−0.488, p=0.0070), PISQ-12 (r=0.643, p=0.0013)], more severe depression [BDI-II: PISQ-12 (r=0.474, p=0,0258)], deteriorated quality of life [HAQ: PISQ-12 (r=0.476, p=0.0252)], and worse ability to perform physical activities [HAP: FSFI (r=0.437, p=0.0417), BISF-W (r=0.451, p=0.0351), PISQ-12 (r=−0.494,p=0.0195)]. <h3>Conclusions</h3> Women with IIM reported significantly disturbed sexual function, sexual quality of life and pelvic floor function than age-matched healthy controls. Worse scores in IIM were associated with disease activity, physical activity, fatigue, depression and quality of life. <h3>Acknowledgements</h3> Supported by AZV-16-33574A, MHCR 023728, and SVV – 2 60 373. <h3>Disclosure of Interest</h3> None declared.