tbuckley/cabot-search huggingface dataset:
Abstract 2580: Contrasting functions of <i>EPSTI1</i> in human oral and lung squamous cell cancer cell lines - its tumor promoting roles in oral and tumor suppressing roles in lung squamous cell carcinomas
Authors: Meng Meng Fan, Makoto Arai, Akinobu Tawada, Tetsuhiro Chiba, Reo Fukushima, Katsuhiro Uzawa, Masashi Shiiba, Naoya Kato, Hideki Tanzawa, Yuichi Takiguchi
Journal: Cancer Research (2020)

Abstract Introduction: Epithelial-stromal interaction 1 (EPSTI1) is a gene mapped to human chromosome 13q13.3. Recent studies have shown that EPSTI1 regulates many malignant features of cancers. However, the relevance of EPSTI1 to oral squamous cell carcinomas (OSCC) and lung squamous cell carcinoma (LSCC) are not known. The present study aimed to uncover the roles and the underlying mechanisms of EPSTI1 in OSCC and LSCC. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assay were used to evaluate the expression of EPSTI1 in four OSCC cell lines, HSC2, HSC3, HSC3M3 and HSC4, and three LSCC cell lines, LK-2, EBC-1 and H226. In vitro experiments were carried out in parental, their shRNA EPSTI1 knockdown and EPSTI1 overexpressing cells. Cell cycle was evaluated by flow cytometry, and epithelial-to-mesenchymal transition (EMT)-related proteins were evaluated by western blot assay. Changes in expression of EPSTI1-related genes in transfected cells were confirmed by using RT2 Profiler PCR Array Human Cancer Pathway Finder. Results: EPSTI1 was significantly up-regulated in OSCC cell lines, and significantly down-regulated in LSCC cell lines compared to their normal counterparts. Knockdown of EPSTI1 in OSCC cells and overexpression of the gene in LSCC cells suppressed cell proliferation accompanied by cell-cycle arrest in the G1 phase with up-regulation of p21 and down-regulation of CDK2 and cyclin D1. These indicate that EPSTI1 was significantly involved in tumor growth in OSCC and LSCC, but in an opposite direction. Furthermore, EPSTI1 was related to enhanced cell migration and EMT phenotype in OSCC, and it was related to suppressed cell migration and reversed EMT in LSCC. In PCR-array analyses in two OSCC and two LSCC cells, some common genes were regulated similarly in each OSCC and LSCC. Conclusion: EPSTI1 was up-regulated and its down-regulation suppressed the malignant phenotypes, indicating oncogenic roles of the gene in OSCC. In contrast the gene was down-regulated and its up-regulation suppressed the malignant phenotypes, indicating tumor suppressive roles of the gene in LSCC. These findings suggest that EPSTI1 might be a therapeutic target for OSCC and LSCC. Citation Format: Meng Meng Fan, Makoto Arai, Akinobu Tawada, Tetsuhiro Chiba, Reo Fukushima, Katsuhiro Uzawa, Masashi Shiiba, Naoya Kato, Hideki Tanzawa, Yuichi Takiguchi. Contrasting functions of EPSTI1 in human oral and lung squamous cell cancer cell lines - its tumor promoting roles in oral and tumor suppressing roles in lung squamous cell carcinomas [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 2580.
Abstract 3193: <i>FGFR4</i> mutationas a novel biomarker for immunotherapy in patients with non-small cell lung cancer
Authors: Xiangfeng Jin, Xinglong Fan, Kaihua Tian, Hanlin Xu, Nan Ge, Yafei Wang, Shiyue Zhang, Hui Chen, Shaohua Yuan, Kai Wang
Journal: Cancer Research (2020)

Abstract Background: Cancer immunotherapy, especially immune checkpoint inhibitors (ICIs), has provided a remarkable antitumor effect in non-small cell lung cancer (NSCLC), but only a limited number of patients can derive durable benefit. Therefore, more accurate biomarkers are highly needed. The fibroblast growth factor receptor (FGFR) family of receptor tyrosine kinases is comprised of 4 members (FGFR1-4) that mediate the function of the FGFR ligand family. Although the genomic alterations (GAs) of FGFRs were frequently detected by targeted next-generation sequencing (NGS) and considered as potent oncogenes, their correlation with recognized immune biomarkers and predictive value for ICIs response in NSCLC remains unclear. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor and matched blood samples of 3433 NSCLC patients from OrigiMed were collected for targeted NGS panel sequencing from December 2017 to January 2019. GAs including single nucleotide variations, short and long insertions/deletions, copy number variations, and gene rearrangements were assessed. Genomic data and ICIs treatment outcome of 2 cohorts of NSCLC patients were derived from The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center (MSKCC) databases. Results: GAs of FGFR gene family were detected in 5% (172/3433) of patients with NSCLC in the OrigiMed database, including 84 FGFR1 GAs, 34 FGFR4 GAs, 28 FGFR2 GAs, and 26 FGFR3 GAs. No significant difference was observed in the frequency of FGFR4 GAs within the histologic subtypes. Compared with wild-type (WT), FGFR4 GAs were associated with a significantly higher tumor mutational burden (TMB) (6.55 vs. 4.6 muts/Mb, respectively, p&amp;lt;0.001). Survival analysis from 2 independent cohorts confirmed that patients with FGFR4 GAs had remarkable clinical benefit to ICIs compared with WT patients in both progression free survival (PFS) (13.17 months vs 3.17 months, respectively, p=0.025) and durable clinical benefit (DCB) (80% vs 29.3%, respectively, p=0.03). Furthermore, FGFR4 GAs were an independent risk factor of PFS (HR: 0.22, 95%CI: 0.055-0.92, p=0.037) and overall survival (OS) (HR: 0.23, 95%CI: 0.057-0.92, p=0.038). Conclusion: Our results supported that the FGFR4-mutated NSCLC patients were associated with an increased TMB and favorable response to ICIs. This suggests that GAs of FGFR4 may have implications as a biomarker for guiding ICI treatment. Citation Format: Xiangfeng Jin, Xinglong Fan, Kaihua Tian, Hanlin Xu, Nan Ge, Yafei Wang, Shiyue Zhang, Hui Chen, Shaohua Yuan, Kai Wang. FGFR4 mutationas a novel biomarker for immunotherapy in patients with non-small cell lung cancer [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 3193.
Abstract CT123: Phase I study of a B cell-based and monocyte-based immunotherapeutic vaccine, BVAC-C, in human papillomavirus type 16- or 18-positive recurrent cervical cancer
Authors: Chel Hun Choi, Hyun Jin Choi, Jeong-Won Lee, Eun-Suk Kang, Duck Cho, Byung Kwan Park, Yong-Man Kim, Dae-Yeon Kim, Hyungseok Seo, Myunghwan Park, Wuhyun Kim, Ki-Young Choi, Taegwon Oh, Chang-Yuil Kang, Byoung-Gie Kim
Journal: Cancer Research (2020)

Abstract BVAC-C is a B cell-based and monocyte-based immuno-therapeutic vaccine transfected with a recombinant human papillomavirus (HPV) 16/18 E6/E7 gene and loaded with alpha-galactosyl ceramide, which is a natural killer T cell ligand. This phase I study sought to determine the tolerability and immunogenicity of BVAC-C in platinum-resistant recurrent cervical cancer patients. Patients with HPV 16-positive or 18-positive recurrent or persistent cervical cancer who had received at least one prior platinum-based combination chemotherapy were enrolled. BVAC-C was injected intravenously three times every four weeks, and dose escalation was planned in a three-patient cohort design at doses of 1×107, 4×107, or 1×108 cells/dose. Eleven patients were enrolled, and six (55%) patients had received two or more lines of platinum-based chemotherapy prior to enrollment. Treatment-related adverse events (TRAEs) were observed in 21 cycles. Most TRAEs were mild fever (n = 6.55%) or myalgia (n = 4.36%). No dose-limiting toxicities occurred. The overall response rate was 11% among nine patients evaluable, and the duration of response was 10 months. Five patients (56%) achieved a stable disease for 4.2-11 months as their best overall response. The median progression-free survival in all patients was 6.8 months (95% CI, 3.2 to infinite months), and the overall survival rate at 6 and 12 months was 89% (95% CI, 71 to 100%) and 65% (95% CI, 39 to 100%), respectively. BVAC-C induced the activation of natural killer T cells, natural killer cells, and HPV 16/18 E6/E7-specific T cells upon vaccination in all patients evaluated. BVAC-C was well tolerated and demonstrated a durable anti-tumor activity with an immune response in HPV 16-positive or 18-positive recurrent cervical carcinoma patients. A Phase 2 efficacy trial is currently underway. Citation Format: Chel Hun Choi, Hyun Jin Choi, Jeong-Won Lee, Eun-Suk Kang, Duck Cho, Byung Kwan Park, Yong-Man Kim, Dae-Yeon Kim, Hyungseok Seo, Myunghwan Park, Wuhyun Kim, Ki-Young Choi, Taegwon Oh, Chang-Yuil Kang, Byoung-Gie Kim. Phase I study of a B cell-based and monocyte-based immunotherapeutic vaccine, BVAC-C, in human papillomavirus type 16- or 18-positive recurrent cervical cancer [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 CT123.
DIAGNOSTIC ACCURACY OF HAND AND FOOT MRI FOR EARLY RHEUMATOID ARTHRITIS
Authors: W.P. Nieuwenhuis, H.W. van Steenbergen, L. Mangnus, E.C. Newsum, J.L. Bloem, T.W.J. Huizinga, L. Cessie, M. Reijnierse, A.H.M. van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2016)
Abstract 4370: Lasofoxifene alone or in combination with palbociclib as an effective treatment for therapy-resistant ER-positive metastatic breast cancer
Authors: Muriel Laine, Justyna D. Kurleto, Marianne E. Greene, Linda Phung, Barry S. Komm, Geoffrey L. Greene
Journal: Cancer Research (2020)

Abstract Patients with Estrogen Receptor positive (ER+) metastatic breast cancer (MBC) are currently treated with fulvestrant, a selective estrogen receptor degrader (SERD), or a combination of fulvestrant and palbociclib, a CDK4/6 inhibitor. Approximately 25-40% of patients with MBC have activating mutations in the ERα ligand-binding domain. The two most common mutations are Y537S and D538G, which confer constitutive activity to ERα, resulting in AI/tamoxifen/fulvestrant resistance. Lasofoxifene, a selective estrogen receptor modulator (SERM), was developed for the treatment of vaginal atrophy and osteoporosis. Previous studies from this lab, performed in a mutant ERα MCF-7 xenograph MBC mouse model, showed that lasofoxifene was significantly more effective than fulvestrant at inhibiting tumor growth, as well as metastasis to the lung and liver. In the current dose/response study, we compared the efficacy of lasofoxifene + palbociclib combinations to fulvestrant + palbociclib combinations. Engineered and luciferase-GFP tagged MCF-7 Y537S cells were injected into the mammary ducts of NSG mice (MIND model) and tumor progression was monitored by live luminescence imaging of primary tumors as well as ex vivo imaging of metastatic sites at study endpoint. Our results showed that all dose combinations of lasofoxifene + palbociclib were more effective than fulvestrant + palbociclib at inhibiting primary tumor growth as well as bone, lung, liver and brain metastasis. These data strongly suggest that patients with ERα+ MBC would benefit from orally delivered lasofoxifene + palbociclib therapy and that this combination could be superior to fulvestrant + palbociclib. Citation Format: Muriel Laine, Justyna D. Kurleto, Marianne E. Greene, Linda Phung, Barry S. Komm, Geoffrey L. Greene. Lasofoxifene alone or in combination with palbociclib as an effective treatment for therapy-resistant ER-positive metastatic breast cancer [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 4370.
Abstract 2958: ONC206, an imipridone derivative, induces cell death through activation of the integrated stress response in serous endometrial cancer in vitro
Authors: Yingao Zhang, Yu Huang, Yajie Yin, Yali Fan, Katherine Tucker, Allison Staley, Varun Prabhu, Joshua Allen, Chunxiao Zhou, Victoria Bae-Jump
Journal: Cancer Research (2020)

Abstract Objectives: ONC206 (Oncoceutics) is a selective dopamine receptor D2 (DRD2) antagonist and an analogue of ONC201, an imipiridone currently being investigated in phase II clinical trials for serous endometrial cancer (EC). ONC206 has been shown to inhibit cell proliferation through activation of the integrated stress response (ISR) and apoptosis in brain, breast, and colorectal cancer cell lines. Thus, we investigated the efficacy of ONC206 for serous EC as well as its underlying mechanism of action. Methods: The serous EC cell lines, ARK1 and SPEC-2, were used. Cellular proliferation was measured using MTT assay. Cleaved caspase-3 and 9, markers of apoptosis, were assessed by ELISA assays. Adhesion and invasion were assessed by laminin and wound healing assays, respectively. Relative In vitro ISR was estimated by ROS and JC-1 assays. Western immunoblotting evaluated effects of ONC206 on proteins central to cellular stress and invasion. All statistical analyses were performed using the software Prism 8 (GraphPad). Results: ONC206 inhibited cellular proliferation in a dose-dependent manner and was more potent than ONC201 in ARK1 (IC50=0.33uM vs IC50=1.59uM) and SPEC-2 (IC50=0.24uM vs IC50=0.81uM) cell lines. Treatment with ONC206 decreased JC-1 fluorescence (p=0.001-0.01), and increased ROS production (p&amp;lt;0.001), cleaved caspase-3 (p=0.008-0.02), and caspase-9 (p=0.02-0.04) activity in both cell lines. ONC206 increased expression of the stress proteins ATF4, PERK, and BiP. Adhesion (p=0.01-0.02) and wound healing (p&amp;lt;0.001) were significantly impaired after treatment with ONC206 and was accompanied by decreases in proteins Slug, Snail, Vimentin, and VEGF-C. Pretreatment with stress inhibitor n-acetylcysteine (NAC) significantly attenuated the efficacy of ONC206 on ROS production (p=0.001-0.01), wound healing (p&amp;lt;0.001), and proliferation (p=0.001-0.002) in both cell lines. Conclusions: Our results suggest that ONC206 demonstrates nanomolar potency for the inhibition of proliferation in serous EC cell lines. Specifically, ONC206 utilizes ISR activation as a significant pathway in the propagation of its anti-proliferative and anti-metastatic effects. Thus, ONC206 may be a promising agent in serous EC which has limited treatment options. Citation Format: Yingao Zhang, Yu Huang, Yajie Yin, Yali Fan, Katherine Tucker, Allison Staley, Varun Prabhu, Joshua Allen, Chunxiao Zhou, Victoria Bae-Jump. ONC206, an imipridone derivative, induces cell death through activation of the integrated stress response in serous endometrial cancer in vitro [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 2958.
Variation in Acute Care Rehabilitation and 30-Day Hospital Readmission or Mortality in Adult Patients With Pneumonia
Authors: Janet K. Freburger, Aileen Chou, Tracey Euloth, Beth Matcho
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Pneumonia often leads to functional decline during and after hospitalization and is a leading cause of hospital readmissions. Physical and occupational therapists help improve functional mobility and may be of help in this population. <h3>Objective</h3> To evaluate whether use of physical and occupational therapy in the acute care hospital is associated with 30-day hospital readmission risk or death. <h3>Design, Setting, and Participants</h3> This cohort study included the electronic health records and administrative claims data of 30 746 adults discharged alive with a primary or secondary diagnosis of pneumonia or influenza-related conditions from January 1, 2016, to March 30, 2018. Patients were treated at 12 acute care hospitals in a large health care system in western Pennsylvania. Data for this study were analyzed from September 2019 through March 2020. <h3>Exposures</h3> Number of physical and occupational therapy visits during the acute care stay categorized as none, low (1-3), medium (4-6), or high (&gt;6). <h3>Main Outcomes and Measures</h3> Outcomes were 30-day hospital readmission or death. Generalized linear mixed models were estimated to examine the association of therapy use and outcomes, controlling for patient demographic and clinical characteristics. Subgroup analyses were conducted for patients older than 65 years, for patients with low functional mobility scores, for patients discharged to the community, and for patients discharged to a post–acute care facility (ie, skilled nursing or inpatient rehabilitation facility). <h3>Results</h3> Of 30 746 patients, 15 507 (50.4%) were men, 26 198 (85.2%) were White individuals, and the mean (SD) age was 67.1 (17.4) years. The 30-day readmission rate was 18.4% (5645 patients), the 30-day death rate was 3.7% (1146 patients), and the rate of either outcome was 19.7% (6066 patients). Relative to no therapy visits, the risk of 30-day readmission or death decreased as therapy visits increased (1-3 visits: odds ratio, 0.98; 95% CI, 0.89-1.08; 4-6 visits: odds ratio, 0.89; 95% CI, 0.79-1.01; &gt;6 visits: odds ratio, 0.86; 95% CI, 0.75-0.98). The association was stronger in the subgroup with low functional mobility and in individuals discharged to a community setting. <h3>Conclusions and Relevance</h3> In this study, the number of therapy visits received was inversely associated with the risk of readmission or death. The association was stronger in the subgroups of patients with greater mobility limitations and those discharged to the community.
Trends in match injury risk in professional male rugby union: a 16-season review of 10 851 match injuries in the English Premiership (2002–2019): the Professional Rugby Injury Surveillance Project
Authors: Stephen W West, Lindsay Starling, Simon Kemp, Sean Williams, Matthew Cross, Aileen Taylor, John H M Brooks, Keith A Stokes
Journal: British Journal of Sports Medicine (2020)

Objectives The Professional Rugby Injury Surveillance Project is the largest and longest running rugby union injury surveillance project globally and focuses on the highest level of rugby in England. Methods We examined match injuries in professional men’s rugby over the period 2002/2003 to 2018/2019 and described trends in injuries over this time. Results Over the period 2002/2003–2018/2019, 10 851 injuries occurred in 1 24 952 hours of match play, equating to a mean of 57 injuries per club per season and one injury per team per match. The mean incidence, severity (days absence) and burden (days absence/1000 hours) of injury were 87/1000 hours (95% CI 82 to 92), 25 days (95% CI 22 to 28) and 2178 days/1000 hours (95% CI 1872 to 2484), respectively. The tackle accounted for 43% injuries with running the second most common activity during injury (12%). The most common injury location was the head/face with an incidence of 11.3/1000 hours, while the location with the highest overall burden was the knee (11.1 days/1000 hours). Long-term trends demonstrated stable injury incidence and proportion of injured players, but an increase in the mean and median severity of injuries. Concussion incidence, severity and burden increased from the 2009/2010 season onwards and from 2011 to 2019 concussion was the most common injury. Conclusion The rise in overall injury severity and concussion incidence are the most significant findings from this work and demonstrate the need for continued efforts to reduce concussion risk as well as a greater understanding of changes in injury severity over time.
Abstract 1127: Adarza's ZIVA multiplex protein detection platform utilizes a label-free technology to simultaneously monitor murine and human inflammation cytokines in a CAR-T model system
Authors: Jon J. Schmuke, Alun Carter, You Zhou, Ernest Mueller, Matt Cooper
Journal: Cancer Research (2020)

Abstract We have used Arrayed Imaging Reflectometry (AIR™), a label-free protein microarray technology that relies on the target binding-induced perturbation of an antireflective coating on the surface of a silicon biosensor, to create a multiplex antibody array for the detection of human and murine serum cytokines and inflammatory markers. The biosensor is capable of providing quantitative protein concentrations, with limits of detection in the low picograms per mL. Provided in a standard 96-well microplate format, the label-free nature of the array enables flexible creation of standard or custom panels for development of model systems. Here, we demonstrate a custom 22 plex panel developed in collaboration with WUGEN Inc. to provide multi-species cytokine analysis in humanized CAR-T cell models for the evaluation of biologic product efficacy and safety. Samples from in vitro and in vivo models developed for the evaluation of CAR-T activity were analyzed and demonstrated a novel platform for concurrent cross-species cytokine analysis on a single array. Results are evaluated for sensitivity, precision, and accuracy with ZIVA assays comparable to traditional ELISAs. With array capabilities from low to hundreds of plex combined with a hands-free, automation-friendly workflow enabled by the ZIVA instrument, the technology has been designed for the ultimate user-experience. Citation Format: Jon J. Schmuke, Alun Carter, You Zhou, Ernest Mueller, Matt Cooper. Adarza's ZIVA multiplex protein detection platform utilizes a label-free technology to simultaneously monitor murine and human inflammation cytokines in a CAR-T model system [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 1127.