tbuckley/cabot-search huggingface dataset:
Abstract B73: The search for EGFL6 receptor: Implications for tumor angiogenesis
Authors: Mana Taki, Kyung Hee Noh, Lingegowda S. Mangala, Ningyan Zhang, Zhiqiang An, Anil K. Sood
Journal: Clinical Cancer Research (2020)

Abstract Objective: EGFL6, epidermal growth factor (EGF)-like domain multiple 6, has been found to be an important target for antiangiogenesis approaches. However, its receptor is not fully known and is the focus of the current work. Method: We first isolated endothelial cells from 10 high-grade serous ovarian cancers, 5 normal ovarian tissues, and 7 healing wound patient samples, and searched for genes selectively expressed in tumor endothelial cells. For receptor studies, we performed an unbiased antibody array for human phospho-RTKs with EGFL6 treatment. Results: EGFL6 was found to be highly expressed in tumor endothelial cells, but not in wound endothelial cells. EGFL6 promoted tumor angiogenesis by increasing tube formation and migration ability of tumor endothelial cells via Tie2, which is expressed on tumor endothelial cells. Moreover, we developed new EGFL6-blocking antibodies, which reduced tumor angiogenesis and in vivo tumor growth without impairing wound healing. Human phospho-RTK array showed that EGFR could be a candidate receptor for EGFL6. Furthermore, EGL6 activated EGFR expressed on tumor cells and promoted invasion ability of tumor cells by 2-fold. Interestingly, EGFL6 secreted from tumor endothelial cells increased the mRNA expression of EGFL6 in tumor cells, which suggests that there may be a positive regulatory loop between endothelial and tumor cells. Conclusion: EGFL6 could be a promising target for development of antiangiogenesis therapies. Citation Format: Mana Taki, Kyung Hee Noh, Lingegowda S. Mangala, Ningyan Zhang, Zhiqiang An, Anil K. Sood. The search for EGFL6 receptor: Implications for tumor angiogenesis [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 B73.
Managing therapeutic resistance in breast cancer: from the lncRNAs perspective
Authors: Liyuan Peng, Jingwen Jiang, Bo Tang, Edouard C Nice, Yuan-Yuan Zhang, Na Xie
Journal: Theranostics (2020)

Breast cancer (BC) is the most common female malignancy and the second leading cause of cancer-related death worldwide. In spite of significant advances in clinical management, the mortality of BC continues to increase due to the frequent occurrence of treatment resistance. Intensive studies have been conducted to elucidate the molecular mechanisms underlying BC therapeutic resistance, including increased drug efflux, altered drug targets, activated bypass signaling pathways, maintenance of cancer stemness, and deregulated immune response. Emerging evidence suggests that long noncoding RNAs (lncRNAs) are intimately involved in BC therapy resistance through multiple modes of action. Therefore, an in-depth understanding of the implication of lncRNAs in resistance to clinical therapies may improve the clinical outcome of BC patients. Here, we highlight the role and underlying mechanisms of lncRNAs in regulating BC treatment resistance with an emphasis on lncRNAs-mediated resistance in different clinical scenarios, and discuss the potential of lncRNAs as novel biomarkers or therapeutic targets to improve BC therapy response.
FRI0175 Clinical manifestations of antiphospholipid syndrome in females with obstetric pathology and antiphospholipid antibodies
Authors: LA Krysova, OM Lesnyak, NV Putylova, None Remizova, LN Yurchenko
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> Antiphospholipid antibodies (APA) were studied in 94 women with a history of reccurent fetal loss and other obstetric complications associated with antiphospholipid syndrome (APS) such as fetal growth retardation, pre-eclampsia, intrauterine fetal death. <h3>Methods</h3> <h3>Results</h3> APA were found in 43,6% of them: lupus anticoagulant (LA) in 24,5%; anticardiolipin antibodies (aCL) ? in 10,6% and 8,5% had LA and aCL mixture. Only 4,5% of studied women had moderate or high levels of IgG aCL. All women were examined in order to find extragenital manifestations of APS. Clinical features associated with APS including reccurent miscarriages were found in 81,6% women with APA circulation. Extragenital features of APS had 45,5% patients: reccurent arterial or venous thrombosis, thrombocytopenia in 20,4% cases. 25,1% women had possible APS features such as livedo reticularis, damage of cardiac valves, stroke, transient ischaemic attacks, migraine, leg ulcers, syndrome Reino. 29,5% APA-positive women had arterial hypertension. The most serious vascular complications took place in group with high and moderate levels of IgG aCL. One case of systemic lupus erythematosus was diagnosed (according to the American Rheumatism Association criteria). <h3>Conclusion</h3> Women with APA circulation had not only obstetical complications of APS. In 45,5% of them definite and possible features of this pathology were found.
AB0162 New measurement technique for platelet microparticles from the patients with total hip arthroplasty after total
Authors: H Kikuchi, M Saitoh, M Oh, H Nishisaka, T Matsushita, S Sohen
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Platelet microparticles (PMPs) including glycoprotein 2b/3a and 1b etc were activated by vascular injury, shear stress and other factors. Mainly PMPs play procoagulant activity which indicate the capability of attachment and thrombophilia. We demonstrated that the increasement for PMPs from the patients after orthopaedic surgery using flowcytometry. <h3>Objectives</h3> To compare the new technique of the sandwich immunoassay method using against glycoprotein 1b with conventional flowcytometry (FACS, Becton Dickson) reported by Nomura <i>et al</i>.<sup>1</sup> for measurement of PMPs at same time on orthropaedic patients. <h3>Methods</h3> Collect the platelet rich plasma for each samples. The levels of PMPs were measured using immunoassay method and flowcytometry from five patients who received cement less type total hip arthroplasty, on before and after 1st and the 7th post-operative day. <h3>Results</h3> The levels of PMPs before operation were 4.4–13.1/million platelets (FACS), 6.1–22.7/thousand platelets in immunoassay. Correlation between FACS and immunoassay for measuring the levels of PMPs was demonstrated (r2 = 0.457, p = 0.046). The ratio of PMPs increased 130–182% on 1st and 80–311% on 7th operative day. <h3>Conclusion</h3> The new measurement technique using immunoassay method (select the platelet glycoprotein 1b) for PMPs is easy, quick and useful for the evaluation of hypercoagulative change from the patients after total hip arthroplasty. <h3>Reference</h3> Nomura S, Nakamura T, Cone J, <i>et al</i>. Cytometric analysis of high shear induced platelet microparticles and effect of cytokines on microparticle generation. Cytometry 2000;40:173–81
Abstract 19132: A Pharmacodynamic Study of a Personalized Strategy for P2Y12 Inhibition Versus Ticagrelor in Reducing Ischemic and Bleeding Risk - The RAPID MANAGE Study
Authors: Derek Y So, Marie Lordkipanidze, Ruth McPherson, Jordan Bernick, George A Wells, Jean-Francois Tanguay
Journal: Circulation (2017)

Background: Multiple risk factors including demographics and genotypes have been associated with clopidogrel high on-treatment platelet reactivity (HPR). Ticagrelor has increasingly been adopted as...
Covid-19: Hydrocortisone can be used as alternative to dexamethasone, review finds
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Covid-19: Hydrocortisone can be used as alternative to dexamethasone, review finds Elisabeth MahaseHydrocortisone can be used as an alternative to dexamethasone to treat patients severely ill with covid-19, researchers have said after reviewing the latest data.
RETRACTED: Amelioration of imiquimod-induced psoriasis-like dermatitis in mice by DSW therapy inspired hydrogel
Authors: Xiang He, Bing Zhu, WeiJia Xie, Yu He, Jian Song, Yi Zhang, Chi Sun, Hao Li, QiYu Tang, XinXin Sun, Yanni Tan, Yong Liu
Journal: Bioactive Materials (2020)

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of all the Authors, the Editor-in-Chief and the owner of the journal. The article has been retracted because of the authors recently re-conducted partly the experiments, and found that the anti-bacteria behavior of Rb+ was not reproducible. As shown in Fig. 1 (see enclosed file), at a centration as high as 200 mM, the addition of single Rb+ does not show anti-bacteria effect. In Fig. 2 (see enclosed file), the authors prepared a mixed solution containing Rb+, Mg2+ and Zn2+ with concentrations close to those (12 h) in the article, and found that the mixed solution does not show anti-bacterial effect either. The two figures indicate that the anti-bacteria effect of Rb+ is not conclusive, which seriously impairs the rigidity of the paper. Considering complex factors influencing the experiments with hydrogels, there might be other effects on the anti-bacteria behavior. However, since the anti-bacteria effect of Rb+ is incorrect, the authors would like to retract the published article.
Gene expression profile of Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) reveals murine targets for preclinical development of human prostate cancer therapy
Authors: Kerstyn Haram, Heidi Peltier, Bin Lu, Towia Libermann, Bob Choy, Hasan Otu, Gary Latham, Martin Sanda
Journal: Cancer Research (2007)

3882  Introduction and Objective: A persistent obstacle to translation of preclinical mouse studies to effective human prostate cancer therapy is a lack of defined molecular expression patterns in mouse models that correspond to the human counterpart. TRAMP mice have been widely studied, but TRAMP prostate microarray data are not yet publicly available. We sought to generate an open source TRAMP microarray dataset and to use this array to identify differentially expressed genes from human prostate cancer that have concordant expression in TRAMP tumors, and thereby represent lead targets for preclinical therapy development.  Methods: Affymetrix Mouse 430 2.0 chips were used for microarrays of total RNA from 8 TRAMP tumors and 9 normal prostates (ventral and dorsolateral lobes). Arrays were analyzed by dChip using an Unweighted Pair Group Method with Arithmetic-mean and a 90% lower confidence bound (LCB) of the fold change (FC) between the groups. A subset of differentially expressed genes were validated by SYBR Green QRT-PCR. Differentially expressed TRAMP genes were analyzed for concordant expression in publicly available human prostate array datasets and a subset of resulting genes was analyzed by QRT-PCR.  Results: At LCB = 1.2, 3870 probe sets showed upregulated and 2945 showed downregulated transcripts. Of 25 gene products identified by literature search as differentially expressed protein or transcipt in TRAMP, 15 were confirmed in our microarray and 8 were validated by QRT-PCR. Cross-referencing differentially expressed TRAMP genes to public human prostate array datasets revealed 66 genes with concordant expression in mouse and human prostate cancer; 10 genes differentially expressed between primary tumor and normal and 56 between metastases and normal. Two genes, Sox4 and Tubb2a, of these 10 were validated by QRT-PCR.  Conclusion: We report a TRAMP microarray dataset validated by QRT-PCR of a gene subset that showed external validity in consistency of expression patterns with previous gene-specific TRAMP studies. Concordance analysis between TRAMP and human prostate cancer associated genes supports utility of the model and suggests 66 molecular targets for preclinical therapy.
Genomic subtypes may predict the risk of central nervous system recurrence in diffuse large B-cell lymphoma
Authors: Thomas A. Ollila, Habibe Kurt, Jozal Waroich, John Vatkevich, Ashlee Sturtevant, Nimesh R. Patel, Patrycja M. Dubielecka, Diana O. Treaba, Adam J. Olszewski
Journal: Blood (2020)
Sexual harassment and suicide
Authors: Urmimala Sarkar, Shirin Hemmat, Eleni Linos
Journal: BMJ (2020)

The high prevalence and significant adverse effects of workplace sexual harassment have become increasingly clear in the wake of the #MeToo movement.In the linked prospective study, Magnusson Hanson and colleagues convincingly show excess rates of suicide attempts and deaths among people reporting workplace sexual harassment (doi:10.1136/bmj.m2984). 1 These results persist after extensive adjustment, including sex, country of birth, family type, education, income, baseline mental health, and working conditions.Importantly, neither the incidence nor the association with suicidality are limited to women.Although we agree with the authors in exercising caution in interpreting their findings, this large prospective, population based cohort design represents the most rigorous approach to examine this question, and we are unlikely to generate more definitive evidence of a causal relation between workplace sexual harassment and suicide.
Abstract 627: Evaluating the efficacy of enzalutamide and the development of resistance in a preclinical mouse model of type-I endometrial carcinoma
Authors: Christopher Steven Koivisto, Parrish Melodie, Bonala Santosh, Soo Ngoi, Georges J. Nahhas, Bei Liu, Adrian Torres, James Gallagher, Rebekah Snchez-Hodge, Victor Zeinner, David Cohn, Floor Backes, Paul Goodfellow, Helen Chamberlin, Gustavo Leone
Journal: Cancer Research (2020)

Abstract Androgen Receptor (AR) signaling is a critical driver of hormone-dependent prostate cancer and has also been proposed to have biological activity in female hormone-dependent cancers, including type I endometrial carcinoma (EMC). In this study, we evaluated the preclinical efficacy of a third-generation AR antagonist, enzalutamide, in a genetic mouse model of EMC, Sprr2f-Cre;Ptenfl/fl. In this model, ablation of Pten in the uterine epithelium leads to localized and distant malignant disease as observed in human EMC. We hypothesized that administering enzalutamide through the diet would temporarily decrease the incidence of invasive and metastatic carcinoma, while prolonged administration would result in development of resistance. Short-term treatment with enzalutamide reduced overall tumor burden through increased apoptosis but failed to prevent progression of invasive and metastatic disease suggesting that AR signaling may have biphasic, oncogenic and tumor suppressive roles in EMC. Enzalutamide treatment increased Progesterone Receptor (PR) expression within both stromal and tumor cell compartments. Prolonged administration of enzalutamide decreased apoptosis, increased tumor burden and resulted in the clonal expansion of tumor cells expressing high levels of p53 protein, suggestive of acquired Trp53 mutations. In conclusion, we show that enzalutamide induces apoptosis in EMC but has limited efficacy overall as a single agent. Induction of PR, a negative regulator of endometrial proliferation, suggests that adding progestin therapy to enzalutamide administration may further decrease tumor burden and result in a prolonged response. Citation Format: Christopher Steven Koivisto, Parrish Melodie, Bonala Santosh, Soo Ngoi, Georges J. Nahhas, Bei Liu, Adrian Torres, James Gallagher, Rebekah Snchez-Hodge, Victor Zeinner, David Cohn, Floor Backes, Paul Goodfellow, Helen Chamberlin, Gustavo Leone. Evaluating the efficacy of enzalutamide and the development of resistance in a preclinical mouse model of type-I endometrial carcinoma [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 627.
Abstract 6541: Accounting for immune escape mechanisms in personalized and shared neoantigen cancer vaccine design
Authors: Alexander Myronov, Iga Niemiec, Katarzyna Gruba, Giovanni Mazzocco, Anna Sanecka-Duin, Piotr Skoczylas, Michał Drwal, Jan Kaczmarczyk, Piotr Stepniak
Journal: Cancer Research (2020)

Abstract The purpose of this study is to evaluate the importance of immune escape mechanisms (IEMs) when designing cancer immunotherapeutic strategies. Cancer IEMs induced by negative selective pressure on tumor cells can have dramatic effects on immunotherapy treatment outcome. IEMs occurring during cancer evolution have been shown to facilitate loss of mutation-associated neoantigens (Anagnostou et al. Cancer Discov 2017). These mechanisms include: Loss of Heterozygosity (LOH), underexpression of HLA genes and mutations in the neoantigen presentation machinery. During cancer evolution, the initially arising clonal neoantigens may be shared across many patients, followed by predominantly subclonal private neoantigens. The propensity of shared neoantigens to be clonal makes them promising candidates for the development of off-the-shelf cancer vaccines. In order to optimize patient treatment strategies and qualify patients for either shared or private neoantigen-directed therapy, it is crucial to correctly assess the indication-specific IEMs and neoantigen landscape in both hot and cold tumors. We carry out an extensive analysis of tumor neoantigen landscape from different indications based on TCGA, on Parkhurst et al. Cancer Discov. 2019 and other available data for selected indications (including MEL, NSCLC, CRC, and GBM). Using bioinformatics methods we investigate IEMs and their potential effects on the plasticity of neoantigen repertoires including enrichment of immunogenic neoantigens within the predicted vaccine composition, computed per patient. Immunogenicity is assessed using advanced deep learning models for neoantigen presentation and functional T-cell response prediction (Mazzocco et al., poster presented at SITC 2019). We present the results of the comparison between different cancer indications including CRC, MEL, NSCLC and GBM using TCGA patient data and GI-tract cancer patients with validated T-cell responses. We present the frequency of particular immune evasion events, pointing out the differences in the number and quality of immunogenic neoepitopes (both shared and private) under those conditions and provide summary statistics. As a result, we draw conclusions for vaccine design strategies, which are informed by the investigation of immune evasion events and are tested on selected datasets including experimentally-validated neoantigen responses. Citation Format: Alexander Myronov, Iga Niemiec, Katarzyna Gruba, Giovanni Mazzocco, Anna Sanecka-Duin, Piotr Skoczylas, Michał Drwal, Jan Kaczmarczyk, Piotr Stepniak. Accounting for immune escape mechanisms in personalized and shared neoantigen cancer vaccine design [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 6541.
Associations of CT evaluations of antigravity muscles, emphysema and airway disease with longitudinal outcomes in patients with COPD
Authors: Naoya Tanabe, Susumu Sato, Kazuya Tanimura, Tsuyoshi Oguma, Atsuyasu Sato, Shigeo Muro, Toyohiro Hirai
Journal: Thorax (2020)

Multiple CT indices are associated with disease progression and mortality in patients with COPD, but which indices have the strongest association remain unestablished. This longitudinal 10-year observational study (n=247) showed that the emphysema severity on CT is more closely associated with the progression of airflow limitation and that a reduction in the cross-sectional area of erector spinae muscles (ESM CSA ) on CT is more closely associated with mortality than the other CT indices, independent of patient demographics and pulmonary function. ESM CSA is a useful CT index that is more closely associated with long-term mortality than emphysema and airway disease in patients with COPD.
Abstract 3760: HH2710, a highly potent and selective erk1/2 inhibitor for the treatment of mapk mutant tumors
Authors: Lei Li, Min Huang, Leping Li, Yi Chen, Shuai Tang, Yi Su, Ruiping Dong, Jian Ding, Meiyu Geng
Journal: Cancer Research (2020)

Abstract The mitogen-activated protein kinases (MAPK) pathway, often known as the RAS-RAF-MEK-ERK signal cascade, is the most frequently mutated signal pathway in cancer, which makes the components of this pathway attractive targets for anticancer drug development. The MAPK pathway is aberrantly activated in more than 30% of human cancers through a high frequency of genetic alteration. BRAF mutation has been identified in colorectal (10%), thyroid (∼50%) and melanoma (60%) tumors, whereas RAS is mutated in melanoma (20%), colorectal (50%) and pancreatic (90%) tumors. Thus far, inhibitors targeting the upstream BRAF and MEK have been the focus of past decades and achieved great clinical successes, but remained being challenged by the acquired resistance due to genetic alterations in RAS, BRAF or MEK. Therefore, targeting the downstream ERK is believed to exhibit potential advantages in both effectively shutting down MAPK signaling cascade and overcoming the resistance to upstream targets. Toward that end, we developed a novel ERK1/2 inhibitor, HH2710, which is a highly potent and selective inhibitor of ERK1 and ERK2 with IC50 of 4.5, 4.9 nM, respectively. HH2710 significantly inhibited the downstream RSK phosphorylation in a dose-dependent manner in both BRAF and RAS mutant cancer cell lines. HH2710 strongly inhibited the proliferation of most BRAF mutated cancer cell and a proportion of RAS mutated cells, with IC50s ranging from 0.2 to 4.5 μM. In tumor xenograft models, HH2710 showed significant antitumor activity at the doses of 15, 30, and 60 mg/kg (twice per day, given orally) with the relative tumor volume at the endpoint (T/C value) of 51.0%, 18.1%, and 11.7% respectively, exhibiting improved efficacy over the front runner molecule in clinical development. Summary of pharmacokinetic parameters are listed in Table 1. The full in vitro and in vivo preclinical characterizations of HH2710 will be presented. Table 1, Pharmacokinetic parameters of HH2710 in mouse, SD rats and Beagle dogs ParametersnCmax*nAUC0-t*t1/2TmaxFµg/mLµg•h/mLhh(%)Mouse, PO0.5031.811.12.065Rat, PO0.2691.773.02.068Dog, PO0.3381.642.01.573*nCmax: Cmax/dose; nAUC0-t : AUC0-t/dose Citation Format: Lei Li, Min Huang, Leping Li, Yi Chen, Shuai Tang, Yi Su, Ruiping Dong, Jian Ding, Meiyu Geng. HH2710, a highly potent and selective erk1/2 inhibitor for the treatment of mapk mutant tumors [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 3760.
National Psoriasis Foundation COVID-19 Task Force Guidance for Management of Psoriatic Disease During the Pandemic: Version 1
Authors: Joel M. Gelfand, April W. Armstrong, Stacie Bell, George L. Anesi, Andrew Blauvelt, Cassandra Calabrese, Erica D. Dommasch, Steve R. Feldman, Dafna Gladman, Leon Kircik, Mark Lebwohl, Vincent Lo Re, George Martin, Joseph F. Merola, Jose U. Scher, Sergio Schwartzman, James R. Treat, Abby S. Van Voorhees, Christoph T. Ellebrecht, Justine Fenner, Anthony Ocon, Maha N. Syed, Erica J. Weinstein, Jessica Smith, George Gondo, Sue Heydon, Samantha Koons, Christopher T. Ritchlin
Journal: Journal of the American Academy of Dermatology (2020)