tbuckley/cabot-search huggingface dataset:
THU-041-Immune-metabolism disorder in progression of hepatitis B virus-related acute-on-chronic liver failure characterized by transcriptomics
Authors: Jun Li, Jiang Li, Xi Liang, Lingling Yang, Jiaojiao Xin, Jing Jiang, Jianing Zhang, Dongyan Shi, Tianzhou Wu, Suwan Sun, Yinyun Lu, Beibei Guo, Xingping Zhou, Hozeifa Mohamed Hassan, Xin Chen
Journal: Journal of Hepatology (2019)
FRI-447-Clinical characteristics of liver cirrhosis and hepatocellular carcinoma occuring after Fontan operation
Authors: Jun Sik Yoon, Dong Ho Lee, Eun Ju Cho, Hyo Young Lee, Sun Woong Kim, Young Chang, Yun Bin Lee, Jeong-Hoon Lee, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon
Journal: Journal of Hepatology (2019)
Effect of Human Papillomavirus Vaccine to Interrupt Recurrence of Vulvar and Anal Neoplasia (VIVA)
Authors: Helen C. Stankiewicz Karita, Kirsten Hauge, Amalia Magaret, Constance Mao, Jeffrey Schouten, Verena Grieco, Long Fu Xi, Denise A. Galloway, Margaret M. Madeleine, Anna Wald
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Human papillomavirus (HPV), particularly HPV type 16, causes most anal and vulvar high-grade squamous intraepithelial lesions (HSIL), which are precursors to cancer. After initial treatment of HSIL, more than 30% of patients will have disease recurrence, with even higher recurrence among HIV-positive individuals and men who have sex with men. Recurrences can be debilitating and lead to significant morbidity and medical expense. Observational studies suggest a possible therapeutic benefit of the licensed HPV vaccines in reducing recurrent lesions in previously infected persons. <h3>Objective</h3> To test whether the licensed prophylactic HPV vaccine (Gardasil-9) can reduce the risk of HSIL recurrence by 50% in previously unvaccinated individuals recently treated for anal or vulvar HSIL. <h3>Design, Setting, and Participants</h3> This is a trial protocol for a randomized, double-blind, placebo-controlled, proof-of-concept clinical trial. Eligible participants are aged 27 to 69 at study start and have not received prior HPV vaccination, have had anal or vulvar HSIL diagnosed on or after January 1, 2014, and have no evidence of HSIL recurrence at screening. Persons infected with HIV are eligible for the study provided they are receiving antiretroviral therapy. Target enrollment is 345 individuals. The primary outcome is time to histopathologically confirmed recurrence of HSIL. Differences in the risk for recurrence of HSIL will be evaluated using Cox proportional hazard models. Additional analyses include (1) frequency of HSIL recurrence; (2) role of HPV antibodies in deterring recurrence; (3) role of HPV persistence in recurrence, as measured by HPV genotype or HPV-16 variant lineage determined using swab samples collected at months 0, 18, and 36; and (4) incidence of adverse events. The study will be conducted at the University of Washington Virology Research Clinic from 2017 through 2022. Participants will be followed up for up to 36 months in the clinic, and up to 42 months by telephone. <h3>Discussion</h3> Management of persistent or rapidly recurring anogenital HSIL remains challenging. Results from this study will provide evidence on whether incorporating the nonavalent HPV vaccine into routine care can decrease recurrence of anal and vulvar HSIL. <h3>Trial Registration</h3> ClinicalTrials.gov identifier:NCT03051516
A Systematic Review of Clinical Decision Support Systems for Clinical Oncology Practice
Authors: Pamala A. Pawloski, Gabriel A. Brooks, Matthew E. Nielsen, Barbara A. Olson-Bullis
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Electronic health records are central to cancer care delivery. Electronic clinical decision support (CDS) systems can potentially improve cancer care quality and safety. However, little is known regarding the use of CDS systems in clinical oncology and their impact on patient outcomes. Methods: A systematic review of peer-reviewed studies was performed to evaluate clinically relevant outcomes related to the use of CDS tools for the diagnosis, treatment, and supportive care of patients with cancer. Peer-reviewed studies published from 1995 through 2016 were included if they assessed clinical outcomes, patient-reported outcomes (PROs), costs, or care delivery process measures. Results: Electronic database searches yielded 2,439 potentially eligible papers, with 24 studies included after final review. Most studies used an uncontrolled, pre-post intervention design. A total of 23 studies reported improvement in key study outcomes with use of oncology CDS systems, and 12 studies assessing the systems for computerized chemotherapy order entry demonstrated reductions in prescribing error rates, medication-related safety events, and workflow interruptions. The remaining studies examined oncology clinical pathways, guideline adherence, systems for collection and communication of PROs, and prescriber alerts. Conclusions: There is a paucity of data evaluating clinically relevant outcomes of CDS system implementation in oncology care. Currently available data suggest that these systems can have a positive impact on the quality of cancer care delivery. However, there is a critical need to rigorously evaluate CDS systems in oncology to better understand how they can be implemented to improve patient outcomes.
Correction of thyroid status of female rats in development of lung metastasis.
Authors: Lidia K. Trepitaki, Irina V. Kaplieva, Elena Mikhaylovna Frantsiyants, Irina Igorevna Gorina, Lyudmila Dmitriyevna Tkalya
Journal: Journal of Clinical Oncology (2015)

e22000 Background: Development of primary tumor and its metastases is accompanied by hormonal misbalance in the body. An important role of the thyroid gland in increasing metastasis risk is well known. The purpose of the study was to prevent lung metastasis of malignant tumor by correcting the level of thyroid hormones. Methods: The study included 20 female rats (Wistаr) with lung metastases. Levels of hormones in blood serum, the thyroid gland and hypophysis were studied after thyroid status correction with a complex heterocyclic iodine-containing compound (HICC) (1,3-diethylbenzimidazole triiodide) since the first day of metastasis: 5 days of treatment with a 2 day interval. Levels of thyroid-stimulating hormone (TSH), free T4 (FT4), free T3 (FT3), total T4 (T4), total T3 (T3) and antibodies to tPO were detected by radioimmunoassay using standard reagents. Results: Hypothyroidism was observed in female rats during lung metastasis. 1 week after HICC correction levels of FT3, FТ4, Т3, TSH and antibodies to tPO in the thyroid gland, TSH in hypophysis and Т4 in blood serum did not differ from levels in intact animals. Levels of FT3 and antibodies to tPO in blood serum reduced by 1.5 and 1.6 times, respectively, in comparison with rats without correction. 2 weeks after HICC correction content of FТ3 and Т4 in the thyroid gland decreased by 3 and 1.8 times, respectively; TSH secretion in hypophysis decreased even more significantly – by 1.8 times. FТ3, FТ4, Т4 and TSH levels became normal in blood serum. Conclusions: HICC correction results in almost complete restoration of the thyroid gland function and thyrotropic function of the hypophysis 1 week after the correction, and in inhibition of the thyroid gland function (hypothyroidism in the group without correction) and thyrotropic function of the hypophysis in 2 weeks, with normalization of all studied indices in blood. Dynamics of thyroid status is accompanied by the absence of lung metastases due to HICC correction.
Multi-platform quality assurance (QA) comparison of next-generation sequencing (NGS) technologies incorporating novel simultaneous mutation and copy number variation (CNV) reporting.
Authors: Paul N. Mainwaring, Christopher Pyke, Darren Korbie, Michael Pheasant, Dennis Gascoigne, Ken Musgrave, Kate O'Neill, Kelly McGrath, Mattias Trau
Journal: Journal of Clinical Oncology (2015)

e22126 Background: We have developed proprietary, innovative methods for the identification of actionable aberrations using NGS of malignant tissues. Prior to commencing prospective decisions based on these technologies, we have established a series of QA programs to validate our entire pipeline, including a) target selection panels b) sequencing technology, c) informatic data analysis for variant calling and CNV. Methods: Breast cancer patient cohort of 50 patients. 45 patients (90%) underwent BCT, 5 (10%) Mastectomy. Median age was 55, 33 (66%) postmenopausal, IDC 36 (72%). TNM Stage: I 27 pts (54%), II 20 pts (40%). IHC: ER Pos 38 (76%), Neg 9 (18%); PR Pos 22 (44%), Neg 11 (22%); HER2 SISH Pos 2 (4%); TNBC 9 (18%). Results: Our informatic pipeline was developed with the LifeTech CCP 409 panel for target selection, sequenced with LifeTech’s Proton sequencer. For the QA trial we designed a custom Qiagen panel overlapping 14% of the CCP targets. The CCP/Proton pipeline was sequenced in parallel to Qiagen/Proton and validation with Qiagen/HiSeq is in progress. The CCP/Proton pipeline identified aberrations coincident with peaks reported by COSMIC 71 (Nov 2014) in 34% of samples, the most common being PIK3CA. 9% were subject to disruptive mutations in tumour suppressor genes and 47% had CNV. 30% of tumour samples had CNV without mutations. Our unique CNV analysis is not reliant on a matching normal sample, requiring only the sequencer variant caller output from the tumour sample and a pool of normal blood result on the same platform. The pipeline is statistically robust and accurately identified the 2 patients assessed through pathology to be HER2+. We also detected the previously reported CNVs at 8q11-23 (10), 1q21-31 (9), 16p13 (8), as well as CNVs at 13q33 (4) and 7q31 (4). Conclusions: Our study provides the requisite QA to enable precision medicine through identification and characterisation of potentially actionable aberrations at the DNA level. Clinical trial information: ACTRN12605000733684. Qiagen CCP Both Validation Hotspots 13 20 12 Disruptions 9 3 2 Clinical Observations Total Samples 53 53 53 with Hot spot mutations 12 18 11 with disruptions 16 5 3 CNV N/A 25 N/A
Real-life experience with the implementation of DLL3 staining and the subsequent treatment with rovalpituzumab tesirine in heavily pretreated SCLC patients
Authors: M.J. Hochmair, C. Weinlinger, H. Fabikan, R. Koger, D. Krenbeck, F. Huemer, O.M. Illini, M. Kulaksiz, A. Valipour, O.C. Burghuber
Journal: Annals of Oncology (2019)

Background: Around 15% of newly diagnosed lung cancer patients are characterized as SCLC mostly with extensive stage disease. While SCLC may be responsive to 1st or 2nd line chemotherapy, there is no approved drug for the 3rd line with guidelines recommending best supportive care. Rovalpituzumab Teserine (Rova-T) is a novel first–in-class antibody-drug conjugate and targets the delta-like protein 3 (DLL3), a newly discovered target highly expressed in SCLC and other high-grade neuroendocrine carcinomas. ROVA-T showed an encouraging single-agent anti-tumor activity and manageable safety profile in Phase 1 and 2 studies. The present study is a retrospective analysis to evaluate DLL3 testing and real-life experience with ROVA-T for patients with an unmet medical need after failure of at least 2 systemic treatments. Methods: DLL3 Immunohistochemistry (VENTANA DLL3 (SP347) Assay) was performed for 68 Patients with high grade neuroendocrine carcinoma (61 SCLC and 7 LCNEC). The percentages of stained tumor cells was determined - TC-counts of < 25% were interpreted as negative, counts of ≥ 25 to < 75% as positive and ≥75% as highly positive. 16 patients were eligible for treatment with Rova-T and received at least 1 of 2 planned cycles with a dose of 0.3 mg/kg. Results: DLL3 staining was seen in most of the patients with high grade neuroendocrine carcinoma, 49 specimens (72.1%) were interpreted as highly positive, 10 specimens (14.7%) were considered positive. 9 (13.2 %) were considered negative, 4 (5,9%) of them showed no staining for IHC. All eligible patients had an ED with an ECOG of 0-1. 2 of the treated patients were DLL3 negative, 4 positive and 10 were highly positive. Of the 2 planned cycles 7 patients received both and 9 received only one due to disease progression or adverse events. Overall, 4 patients (25%) showed a PR, 4 (25%) had SD and 8 developed disease progression (50%). Side effects were manageable. Conclusions: DLL3 staining is frequent in SCLC patients but further studies are needed to proof it to be a useful predictive biomarker. Rova-T seems to be an option for ED SCLC patients in later lines with a high unmet need for treatment and showed a clinical benefit in selected patients with a manageable safety profile. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
A functional kinome screen to identify pathways of anthracycline resistance in patient-derived breast cancer cells.
Authors: Hannah Richards, Olga Nikolova, Kay Gurley, Carla Grandori, Kemp Christopher, Vijayakrishna K. Gadi
Journal: Journal of Clinical Oncology (2015)

11092 Background: Despite 5 decades of generalized anthracycline use in breast cancer, rates of progression following exposure remain very high. In order to identify biologic mechanisms contributing to resistance, we performed high-throughput small interfering RNA (siRNA) screens on breast cancer cells from patients whose disease had progressed after anthracyclines. Methods: Cells were isolated directly from metastatic tumors and peritoneal or pleural effusions from patients with anthracycline-resistant breast cancer (n = 26, recruitment ongoing), expanded in culture, confirmed to be of epithelial origin by expression of keratin and stem cell markers (CD44+, CD24-), and could be grown as organoids. Low passage cells were transfected in triplicate with siRNAs targeting 713 kinases alone (IC0) or in the presence of doxorubicin (IC30, inhibitory concentration 30%) and viability measured at 72 hours. Candidate sensitizer genes were called using the Z-transformed mean normalized viability across all plates, robust Z-score within each plate (-2 > Z > 2), and T-test p-value (p < 0.05). Pathway enrichment was computed for hits using Gene Ontology, KEGG, and Reactome databases. Results: Unsupervised hierarchical clustering of knockdown hits revealed clear separation by doxorubicin exposure for the first 4 patients evaluated (2 luminal b, 2 triple negative cases). Knockdown of 111 kinases resulted in significantly decreased proliferation in the IC0 screen. Knockdown of 228 kinases from the IC30 screen resulted in anthracycline sensitization and the top pathway implicated was ceramide biosynthesis/metabolism. Conclusions: For the first time, we demonstrate the feasibility of an individualized systems medicine approach using high-throughput siRNA screening in specimens directly derived from patients. Our top pathway hit identified was the ceramide pathway, only previously observed in anthracycline resistant cell lines. Larger scale RNAi and targeted agent drugs screens are ongoing in additional patients to validate the ceramide pathway and to identify novel drug targets in patients with anthracycline resistant disease toward our goal of reducing the burden of recurrence.
Quality of life, depression, and end-of-life outcomes in hospitalized patients with advanced cancer.
Authors: Kathryn Elizabeth Hudson, Steven Paul Wolf, Amy Pickar Abernethy, Thomas William LeBlanc
Journal: Journal of Clinical Oncology (2015)

9525 Background: Hospitalized cancer patients are more likely to have advanced disease and are at risk for poor outcomes, yet little is known about their quality of life (QOL) and rates of depression. We aimed to assess QOL, mood, and end-of-life outcomes in this population. Methods: From 2008-10 we enrolled hospitalized patients at Duke University with acute leukemia or stage III/IV solid tumor or lymphoma and whose physician stated that they “would not be surprised if they died in less than one year.” 150 patients completed surveys, including demographics and validated instruments measuring QOL (FACT-G) and mood (brief CES-D). We retrospectively reviewed charts to assess end-of-life outcomes including presence of advance directives, use of palliative care, and rate of death in the hospital. Descriptive statistics, linear regression and sensitivity analyses were performed. Results: Mean FACT-G score was 66.9 (SD 11), 14 points worse than published cancer patient norms. QOL was significantly worse in all FACT-G subscales except for social wellbeing (24.2 vs. 22.1, p < 0.001). 30% of patients (n = 45) had a brief CES-D score of > 4, suggestive of depression. Higher scores were associated with lower performance status (p < .05). Patients with lower education levels had lower QOL (FACT-G 59.9 vs 68.4, p < .05). There were no significant differences between tumor type and performance status, QOL, or depression scores; and there was no association between time until death and QOL or depression. Markers of end-of-life care quality were poor. By this analysis, 86% (127) of patients had died. While physicians correctly estimated death within one year in 69% of cases, only 25% of patients used hospice, and only 2.7% received an in-hospital palliative care consult. 60.5% had a do-not resuscitate order, and 43% of patients died in the hospital. Conclusions: Hospitalized patients with advanced cancer have poor quality of life compared to established cancer patient norms and a high rate of depression. While physicians expected these patients to die within a year, end-of-life quality outcomes were poor. Hospitalized patients with advanced cancer may benefit from interventions aimed at improving mood, quality of life, and end-of-life care.
Abstract 10946: Blockade of NKG2D / NKG2D Ligands Interaction Attenuated Cardiac Remodeling After Myocardial Infarction
Authors: Kotaro Matsumoto, Masanori Obana, Rina Hashizume, Yukari Yokoyama, Shigeru Miyagawa, Tomomi Mohri, Makiko Maeda, Hiroyuki Nakayama, Yoshiki Sawa, Yasushi Fujio
Journal: Circulation (2015)

Background The activating receptor Natural Killer Group 2 member D (NKG2D), expressed on immune cells such as NK, NKT and γδ T cells, contributes to eliminating infected or tumor cells by recognizing NKG2D ligands (NKG2DL). Accumulating evidence demonstrates that immune responses are involved in cardiovascular diseases; however, how cardiomyocyte death is induced by immune reactions in heart failure remains to be fully elucidated. Here, we examined the involvement of NKG2D/NKG2DL-mediated cell death in the progression of heart failure after myocardial infarction (MI). Methods and Results Murine MI was generated by ligating left anterior descending artery. Quantitative reverse transcription polymerase chain reaction (RT-PCR) demonstrated that NKG2DL, especially Rae-1ε, and NKG2D were up-regulated and reached the peak at day 3 (32 fold v.s. control) and day 7 (22 fold v.s. control), respectively, after MI. Moreover, immunohistochemical analysis revealed that Rae-1 was expressed in the infarct and border area of the post-infarcted hearts. To identify the NKG2D-expressing cells which infiltrated post-infarcted myocardium, flow cytometric analysis was performed using anti-CD49b antibody, NK cell marker, or anti-γδ TCR antibody, γδ T cell marker. Intriguingly, NKG2D-expressing immune cells were mainly γδ T cells, but not NK cells. Finally, to examine the pathophysiological role of the NKG2D/NKG2DL interaction in cardiac remodeling, MI mice were intraperitoneally treated with anti-Rae-1ε antibody or control IgG. Anti-Rae-1ε antibody administration suppressed cardiac fibrosis at day 14 after MI compared with control (control: 45.5%, anti-Rae-1ε antibody: 30.2%) assessed by Masson’s trichrome staining. Furthermore, TUNEL staining showed that apoptosis of cardiomyocytes was reduced by anti-Rae-1ε antibody treatment at day 3 after MI. Conclusion Blockade of NKG2D/NKG2DL interaction suppressed cardiac injury and death, preventing the progression of heart failure. NKG2D/NKG2DL could be a novel therapeutic target for heart failure.
FRI-488-Prognostic value of tumor markers after a complete response to transarterial chemoembolization in patients with recurrent hepatocellular carcinoma following curative resection
Authors: Jae Seung Lee, Mi Young Jeon, Tae Seop Lim, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han, Seung Up Kim
Journal: Journal of Hepatology (2019)
Cuboidal tethered cyclodextrin frameworks tailored for hemostasis and injured vessel targeting
Authors: Yaping He, Jian Xu, Xian Sun, Xiaohong Ren, Abi Maharjan, Peter York, Yong Su, Haiyan Li, Jiwen Zhang
Journal: Theranostics (2019)

Rationale: Targeted delivery of therapeutic drugs or imaging agents to injured blood vessels via nanocarriers is likely to be dependent on the particle shape, yet cubic nanoparticle carriers have not been reported for vascular targeting. Here, we demonstrate that cuboidal cyclodextrin frameworks possess superior hemostasis effect and injured vessels targeting compared with spherical counterpart. Methods: Cuboidal and biocompatible γ-cyclodextrin metal-organic frameworks (CD-MOFs) are synthesized, tethered via crosslinking and surface modification with GRGDS peptide (GS5-MOFs). The specific interactions of cubic GS5-MOF nanoparticles with activated platelets were investigated by in vitro platelet aggregation assay and atomic force microscopy measurements (AFM). The hemostatic capacity and injured vessel targeting efficacy were evaluated in vivo. Results: Cuboidal GS5-MOF nanoparticles exhibit enhanced adhesion and aggregation with activated platelets in vitro under static condition and a physiologically relevant flow environment. The cubic GS5-MOF nanoparticles show efficient hemostatic effects with bleeding time and blood loss decrease of 90% and strong injured vessel targeting in vivo, markedly superior to spherical γ-CD nanosponges with the same chemical composition. Conclusions: These results clearly highlight the contribution of the cuboidal shape of GS5-MOFs to the enhanced aggregation of activated platelets and high targeting to damaged vessels. The cuboidal nanoparticle system provides an innovative delivery platform for the treatment and diagnosis of vascular diseases.
Author Correction: Mosaic nanoparticle display of diverse influenza virus hemagglutinins elicits broad B cell responses
Authors: Masaru Kanekiyo, M. Gordon Joyce, Rebecca A. Gillespie, John R. Gallagher, Sarah F. Andrews, Hadi M. Yassine, Adam K. Wheatley, Brian E. Fisher, David R. Ambrozak, Adrian Creanga, Kwanyee Leung, Eun Sung Yang, Seyhan Boyoglu-Barnum, Ivelin S. Georgiev, Yaroslav Tsybovsky, Madhu S. Prabhakaran, Hanne Andersen, Wing-Pui Kong, Ulrich Baxa, Kathryn L. Zephir, Julie E. Ledgerwood, Richard A. Koup, Peter D. Kwong, Audray K. Harris, Adrian B. McDermott, John R. Mascola, Barney S. Graham
Journal: Nature Immunology (2019)