tbuckley/cabot-search huggingface dataset:
Abstract 12162: Association of Symptom Clusters With Mode of Transportation to Emergency Department in Patients Diagnosed With Acute Coronary Syndrome
Authors: Leslie L Davis, Thomas P McCoy, Barbara Riegel, Sharon McKinley, Lynn Doering, Kathleen Dracup, Debra Moser
Journal: Circulation (2015)

Background: Prompt treatment of acute coronary syndrome (ACS) has been shown to reduce mortality and morbidity; yet many patients delay seeking care. In order to receive timely care, symptoms of ACS need to be recognized, interpreted, and acted upon. Patients who experience symptoms matching their expectations and those with correct symptom attribution are more likely to use emergency medical services (EMS) as a means of transportation to the hospital. The connection between symptom type and EMS use has not been fully explored. Purpose: To assess if clusters of presenting symptoms are associated with EMS transportation to the emergency department (ED) in patients with ACS and to evaluate if EMS transportation or symptom clusters are associated with prehospital delay time. Methods: A secondary analysis was conducted from the PROMOTION trial, a randomized controlled trial to reduce patient prehospital delay in ACS. Results: Of the 3,522 subjects with coronary artery disease enrolled, 3,087 completed 2-year follow-up. Of these, 331 subjects visited an ED for ACS symptoms during follow-up. Among the 331, 84% (278) had mode of transportation documented; 44% arrived by EMS. Having classic ACS symptoms (chest pain, pressure, or discomfort) in combination with pain symptoms (AOR=2.66, p = 0.011), classic ACS symptoms in combination with stress symptoms (AOR=2.61, p = 0.007) or classic ACS symptoms in combination with both pain and stress symptoms (AOR=3.90, p = 0.012) were associated with higher odds of arriving to the ED by EMS compared to classic ACS symptoms alone. Among 260 patients with prehospital delay time available, arriving by EMS decreased median delay time by 68.5 minutes compared to those with other transportation, after accounting for symptom clusters, patient and study characteristics (p = 0.002). Symptom clusters did not predict delay time in adjusted modeling (p = 0.952). Conclusion: While chest pain was the most prevalent symptom of ACS for most (85%), these findings suggest that it is the cluster of classic ACS symptoms with other types of symptom that motivate patients to use EMS. With less than half of patients using EMS, further research is needed to better understand how symptom clusters influence care-seeking behavior.
Abstract 1471: Short hairpin RNA-expressing oncolytic adenovirus-mediated inhibition of PDL1 significantly suppresses human cancer cell growth
Authors: Jipo Sheng, Xue Wang, Xiaoming Dong, Jin Fu, Sanmao Kang, Fang Hu
Journal: Cancer Research (2019)

Abstract In cancer immunotherapy, it is known that aberrant expression of immune checkpoint proteins in tumor cells and their resulting immunosuppression in surrounding tumor microenviroment and even in whole immune system represent the crucial limiting factors toward successful cancer treatment. Multiple studies evidenced that oncolytic viruses carrying biological molecule including cytokines, shRNAs and miRNAs relieve or attenuate immunosuppression, and may be a promising way toward curing tumor. In this study we generated an oncolytic adenovirus with expression of shRNA targeting human PDL1. The adenovirus exhibited proliferation activity more than two orders of magnitude higher in human cancer cells than in human normal primary cells. Western blot showed significantly decreased expressing levels of PDL1 protein in human cancer cells upon infection of the PDL1 shRNA expressing-oncolytic virus. FACS assay also showed decreased expression levels of PDL1 on the cell membrane after the infection of same viruses. In vivo experiments in two different genetic backgrounds mouse model &amp;lt;NOD-SCID mice and BALBC nude mice&amp;gt; demonstrated that the PDL1 shRNA expressing adenoviruses lysed the majority of the tumor cells derived from HCT116 colorectal cancer cells that were subcutaneously inoculated. Moreover, the adenoviruses downregulated PDL1 expression levels within the HCT116 colon cell-derived tumor cells, remarkably attenuated immunosuppression surrounding the HCT116 tumor. Consisted with these observations, TIL cell counts in the tumors derived from mice with shRNA expressing oncolytic adenovirus treatment were significantly higher than that from mice in other control groups. The growth of HCT116 colon cell-derived tumor in mice with oncolytic adenovirus treatment was greatly inhibited for a longer period compared with that in mice in other control groups. The oncolytic adenovirus described in this study features highly selective amplification in human tumor cells versus normal cells and inhibition of PDL1 expression in tumor cells, therefore it may be important toward developing novel method for cancer therapy. Citation Format: Jipo Sheng, Xue Wang, Xiaoming Dong, Jin Fu, Sanmao Kang, Fang Hu. Short hairpin RNA-expressing oncolytic adenovirus-mediated inhibition of PDL1 significantly suppresses human cancer cell growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1471.
PPARδ Mediates the Effect of Dietary Fat in Promoting Colorectal Cancer Metastasis
Authors: Dingzhi Wang, Lingchen Fu, Jie Wei, Ying Xiong, Raymond N. DuBois
Journal: Cancer Research (2019)

The nuclear hormone receptor peroxisome proliferator-activated receptor delta (PPARδ) is a ligand-dependent transcription factor involved in fatty acid metabolism, obesity, wound healing, inflammation, and cancer. Although PPARδ has been shown to promote intestinal adenoma formation and growth, the molecular mechanisms underlying the contribution of PPARδ to colorectal cancer remain unclear. Here, we demonstrate that activation of PPARδ induces expansion of colonic cancer stem cells (CSC) and promotes colorectal cancer liver metastasis by binding to the Nanog promoter and enhancing Nanog expression. Moreover, PPARδ mediated the effect of a high-fat diet in promoting liver metastasis and induction of colonic CSC expansion. Our findings uncover a novel role of dietary fats in colorectal cancer metastasis and reveal novel mechanisms underlying PPARδ-mediated induction of CSCs and those responsible for the contribution of dietary fats to colorectal cancer progression. These findings may provide a rationale for developing PPARδ antagonists to therapeutically target CSCs in colorectal cancer. SIGNIFICANCE: These findings show that PPARδ contributes to colorectal cancer metastasis by expanding the CSC population, indicating that antagonists that target PPARδ may be beneficial in treating colorectal cancer.
Abstract 4997: Responsiveness to immune checkpoint inhibitors in RET dependent cancers
Authors: Aparna Hegde, Le Huang, Shuang Liu, Kenneth Hess, Maria Cabanillas, Mimi Hu, Naifa Busaidy, Steven Sherman, George Simon, George Blumenschein, Vassiliki A. Papadimitrakopoulou, David S. Hong, Funda Meric-Bernstam, John Heymach, Vivek Subbiah
Journal: Cancer Research (2019)

Abstract Background: The RET receptor tyrosine kinase can be oncogenically activated by gene fusions or point mutations. Multikinase inhibitors such as cabozantinib, lenvatinib, and vandetanib have demonstrated activity in RET dependent (RET+) malignancies. Recent development of selective RET inhibitors is poised to alter their treatment paradigm. However, the responsiveness of RET+ malignancies to immune checkpoint inhibition (ICI) is unknown. We compared the time to progression (TTP) on ICI with non-ICI therapy in patients with malignancies harboring activating RET mutations/fusions. Methods: A retrospective chart review of all RET+ patients who were referred to the phase 1 clinical trials program at MD Anderson Cancer Center between September 2014 and October 2018 was conducted. Patients who had not discontinued treatment or had discontinued treatment for reasons besides disease progression were censored. Time to progression was estimated using Kaplan-Meier analysis. Results: Out of 72 patients who had received systemic therapy for RET+ malignancies, 39 (54.2%) harbored RET mutations (RETm) and 33 (45.8%) harbored RET fusions (RETf). Nineteen patients (26.4%) received ICI and 53 (73.6%) received non-ICI therapy. Thirty four patients (47.2%) had medullary thyroid cancer, 29 (40.3%) had NSCLC and 9 (12.5%) had other types of cancer. PD-L1 expression was only available for 7 patients of which 5 (71.4%) were positive (≥ 1%). Patients had received a median of 1 (1-7) prior lines of therapy. Overall median TTP (mTTP) was 10.5 months (95% CI 6.7-30.1). Hazard ratio for ICI vs. non-ICI therapy was 1.73 (0.70, 4.26) p=0.25 in patients with RETf and 8.0 (2.27, 28.2) p=0.0025 in patients with RETm. Conclusions: In patients with RET+ malignancies, mTTP was shorter with ICI compared to non-ICI therapy. The effect of type of therapy was dependent on the type of RET pathway aberration, with a statistically significant higher risk of progression in RETm malignancies treated with ICI compared to non-ICI therapy. Time to ProgressionRETTherapyNmTTP (months)Freedom from Progression at 6 months (%)Freedom from Progression at 12 months (%)FusionNon-ICI218.36335FusionICI123.03624MutationNon-ICI3231.98273MutationICI75.6430 Citation Format: Aparna Hegde, Le Huang, Shuang Liu, Kenneth Hess, Maria Cabanillas, Mimi Hu, Naifa Busaidy, Steven Sherman, George Simon, George Blumenschein, Vassiliki A. Papadimitrakopoulou, David S. Hong, Funda Meric-Bernstam, John Heymach, Vivek Subbiah. Responsiveness to immune checkpoint inhibitors in RET dependent cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4997.
Abstract 3120: The novel MEK inhibitor binimetinib decreases cell growth and induces apoptosis in AT/RT
Authors: Shubin Shahab, Jeffrey Rubens, Charles Eberhart, Eric Raabe
Journal: Cancer Research (2019)

Abstract Atypical teratoid/rhabdoid tumors are a class of malignant CNS tumors disproportionately affecting children with limited therapeutic options. Our group has previously demonstrated that the MAP kinase pathway is altered in a large proportion of these tumors and the MEK inhibitor selumetinib decreases cell growth and promotes apoptosis of AT/RT cells. One of the major drawbacks of selumetinib is its poor blood-brain barrier penetration. Binimetinib is a novel MEK inhibitor currently in pediatric phase II clinical trials for low grade glioma that is thought to have improved brain penetration. Here we demonstrate nanomolar levels of binimetinib successfully decreases cell proliferation and induces apoptosis (2-3 fold induction of cleaved Parp) in AT/RT cell lines, suggesting binimetinib could offer a potential avenue for treating these deadly tumors. Citation Format: Shubin Shahab, Jeffrey Rubens, Charles Eberhart, Eric Raabe. The novel MEK inhibitor binimetinib decreases cell growth and induces apoptosis in AT/RT [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3120.
Pharmacological interactions of TKIs with the P-gp drug transport protein.
Authors: Sandra Roche, Kasper Pedersen, Grainne Dunne, Denis Collins, Aoife Devery, John Crown, Martin Clynes, Robert O'Connor
Journal: Journal of Clinical Oncology (2012)

2536 Background: Tyrosine Kinase Inhibitors (TKIs) can interact with drug transport proteins. P-gp is a transporter with two important roles in cancer drug therapy. If overexpressed in tumour cells it can cause drug resistance. However, P-gp, expressed in tissues as part of normal drug clearance mechanisms, is also involved in termination of drug action. Hence, TKI-mediated interactions with P-gp have significant therapeutic consequences. Methods: P-gp over-expressing cancer cell lines were used to determine the inhibitor or substrate status of tyrosine kinase inhibitors (erlotinib, gefitinib, lapatinib, dasatinb, neratinib, afatinib and pazopanib). Cell proliferation assays in combination with a potent P-gp inhibitor, or P-gp substrate were also employed. Findings were augmented using LC-MS-based quantitation of cellular levels of target drugs. Results: We summarise our findings of four distinct interactions with P-gp among various TKIs. Some agents have little interaction at conventional doses; others can act as P-gp inhibitors without being substrates; substrates without being inhibitors or substrates which also prevent the actions of the transporter.Eachof the investigated TKIs has a distinct relationship with P-gp. As examples, lapatinib is an inhibitor but not a substrate, dasatinib is a substrate but not an inhibitor, while pazopanib has little interaction with P-gp. Other agents also have an effect on or are affected by P-gp to varying amounts with some of these interactions likely to be suprapharmacological. Conclusions: P-gp protein has important roles both in resistance and drug toxicology, hence, a clear understanding of the interaction of emerging drugs with this transporter is vital. Agents which are inhibitors of P-gp may have applications in drug resistance circumvention but may also greatly exacerbate the toxicity of concurrently administered P-gp substrate cytotoxics; conversely the activity of P-gp substrate TKIs may be reduced by tumour overexpression of the transporter. Hence in vitro screening of TKI-transporter interactions may identify putative TKI resistance mechanisms, help guide the development of combination schedule trials and/or reducing unwanted treatment side effects.
Soft Bioelectronic Stickers: Selection and Evaluation of Skin‐Interfacing Electrodes
Authors: Pedro Alhais Lopes, Davide Vaz Gomes, Daniel Green Marques, Pedro Faia, Joana Góis, Tatiana F. Patrício, Jorge Coelho, Arménio Serra, Aníbal T. de Almeida, Carmel Majidi, Mahmoud Tavakoli
Journal: Advanced Healthcare Materials (2019)

Abstract Surface biopotentials collected from the human epidermis contain important information about human physiology, such as muscular, heart, and brain activities. However, commercially available wearable biomonitoring devices are generally composed of rigid hardware incompatible with the mechanical compliance of soft human tissues. Thin‐film stretchable e‐skin circuits that can interface the human skin represent an excellent alternative for long‐term wearable biomonitoring. Here, a series of soft and stretchable electrodes are evaluated for their applicability in biopotential sensing. This includes conductive composites made of polydimethylsiloxane (PDMS) as a base substrate and conductive particles, i.e., carbon (cPDMS), silver (AgPDMS), anisotropic z ‐axis conductors made with silver‐coated nickel particles (zPDMS), as well as a combination of a conductive tough hydrogel with PDMS, and finally ultrathin tattoo‐like adhesive poly(vinyl alcohol)‐coated films with stretchable biphasic Ag‐EGaIn electrodes. These electrodes are compared between themselves and against the gold‐standard Ag/AgCl and stainless steel electrodes, in order to assess relative performance in signal‐to‐noise ratio (SNR) during electrocardiography, and electrode‐skin impedance for a range of frequencies. Results show a direct relation between conformity of the electrode–skin interface and the SNR value. An all‐integrated biomonitoring patch with embedded processing and communication electronics, hydrogel electrodes, and a multilayer liquid metal circuit is presented for electromyography.
A retrospective, real-world population-based analysis of treatment patterns and outcomes in adult patients with relapsed/refractory acute myeloid leukemia in Alberta, Canada.
Authors: Michelle N. Geddes, Lalit Saini, Fei Fei Liu, Dimas Yusuf, Kiersten Schwann, Alkarim Billawala, Jessica A. Kurniawan, Winson Y. Cheung, Joseph M. Brandwein
Journal: Journal of Clinical Oncology (2019)

e18505 Background: In order to describe the impact of future targeted therapies on treatment outcomes of patients (pts) with relapsed and/or refractory (RR) acute myeloid leukemia (AML), a better understanding of the clinical management pathway in these pts is needed. We therefore evaluated the treatment patterns and associated outcomes in a real-world cohort of pts with RR-AML using a population-based cancer registry and patient medical records. Methods: Pts newly diagnosed wih AML between January 2013 and December 2016, aged ≥ 18 years were identified from the provincial-wide Alberta Cancer Registry (ACR). Data for pts who met the criteria for RR-AML were assessed by hematologists and were extracted from medical records. RR-AML pts were then categorized as: receiving intensive therapy (IT); receiving non-intensive therapy (NIT); or treated with best-supportive care (BSC) following a diagnosis of RR-AML. Results: 572 AML pts were identified from the ACR, of which 199 met criteria for RR-AML and were included in the analysis (124 males, 75 females; median age at diagnosis of RR-AML 66.8 years; median follow-up 4.7 months). In this RR-AML cohort, 26 (13%) pts received ≥ 2 lines of prior therapy. Unadjusted median overall survival (mOS) was 5.3 months, with a 12-month overall survival rate of 29.6% (95% CI 29.0–30.3%) from the time of RR. Following RR, 46 (23%) pts received IT, 65 (33%) pts were treated with NIT, and 88 (44%) pts received BSC, with unadjusted mOS of 13.8, 9.4, and 2.1 months, respectively ( P &lt; 0.001). When stratified by European LeukemiaNet risk classification at diagnosis, unadjusted mOS was 12.4, 4.7, and 4.0 months for favorable risk, intermediate risk, and adverse risk groups, respectively ( P &lt; 0.01). Conclusions: This retrospective, real-world study in Alberta Canada confirms the poor prognosis reported to date in the RR-AML population. Notably, a large proportion of pts received BSC which was associated with dismal survival outcomes. These data also highlight that effective and tolerable alternatives to current treatment options are urgently needed.
Abstract 265: <i>YWHAZ</i> amplification/overexpression defines aggressive bladder cancer and contributes to chemo-/radio-resistance via deregulation of caspase-mediated apoptosis
Authors: Jim Jinn-Chyuan Sheu, Chia-Cheng Yu, I-Hsuan Chen, Praveen Korla, Grace Ko, Chee-Yin Chai, Chien-Fong Li
Journal: Cancer Research (2019)

Abstract The objective of this study is to characterize the oncogenic roles of a recently identified cancer-associated gene called YWHAZ (also known as 14-3-3 α/ζ ) in urothelial carcinomas of urinary bladder (UCUB). Based on a genomewide study, YWHAZ was found located at the 8q22.3 amplicon and its genetic amplification was predominantly detected in tumors at more advanced stages, muscle-invasive bladder cancer (MIBC). IHC staining confirmed the association of YWHAZ overexpression with higher tumor stages, lymph node/vascular invasion, and mitotic activity. Univariate and multivariate analyses further indicated the prognostic potential of YWHAZ for more aggressive cancer types. Both gene set enrichment analysis (GSEA) and STRING network studies suggest the involvement of YWHAZ in regulating caspase-mediated apoptosis. Ectopic expression of YWHAZ in bladder cells with low YWHAZ levels boosted cells becoming more tolerated toward chemical and ionizing radiation treatments. Gene knockdown by specific shRNA in cells with high YWHAZ levels attenuated the survival activity, resulting in cell growth suppression and cell death. Our data confirmed an essential role of YWHAZ in providing survival signals to sustain cell proliferation during chemo- or radio-therapy. Treatments based on anti-YWHAZ strategies may be beneficial for patients with YWHAZ overexpression. Citation Format: Jim Jinn-Chyuan Sheu, Chia-Cheng Yu, I-Hsuan Chen, Praveen Korla, Grace Ko, Chee-Yin Chai, Chien-Fong Li. YWHAZ amplification/overexpression defines aggressive bladder cancer and contributes to chemo-/radio-resistance via deregulation of caspase-mediated apoptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 265.
2019 ACC/AHA/ASE Key Data Elements and Definitions for Transthoracic Echocardiography
Authors: Pamela S. Douglas, Blase A. Carabello, Roberto M. Lang, Leo Lopez, Patricia A. Pellikka, Michael H. Picard, James D. Thomas, Paul Varghese, Tracy Y. Wang, Neil J. Weissman, Rebecca Wilgus
Journal: Journal of the American College of Cardiology (2019)
Abstract 1857: Proscillaridin A induces apoptosis and suppresses non-small cell lung cancer tumor growth via calcium-induced DR4 up-regulation
Authors: Run-Ze Li, Xing Xing Fan, Xiao- Jun Yao, Elaine L. Leung, Liang Liu
Journal: Cancer Research (2019)

Abstract Non-small cell lung cancer (NSCLC) is the predominant histological type of lung cancer and is characterized by the highest mortality and incidence rates among these types of malignancies. Cardiac glycosides, a class of natural products, have been identified as a potential type of chemotherapeutic agent. This study aims to investigate the anti-cancer effects and the mechanisms of action of Proscillaridin A (P.A) in NSCLC cells. In vitro sodium-potassium pump (Na+/K+ ATPase) enzyme assays indicated that P.A is a direct Na+/K+ ATPase inhibitor. P.A showed potent cytotoxic effects in NSCLC cells at nanomolar levels. Treatment mechanism studies indicated that P.A elevated Ca2+ levels, activated the AMPK pathway and down-regulated phosphorylation of ACC and mTOR. Subsequently, P.A increased death receptor 4 (DR4) expression and down-regulated NF-κB. Interestingly, P.A selectively suppressed EGFR activation in EGFR mutant cells but not in EGFR wild-type cells. In vivo, P.A significantly suppressed tumor growth in nude mice compared to vehicle-treated mice. Compared with the Afatinib treatment group, P.A displayed less pharmaceutical toxicity, as the body weight of mice treated with P.A did not decrease as much as those treated with Afatinib. Consistent changes in protein levels were obtained from Western blotting analysis of tumors and cell lines. Immunohistochemistry analysis of the tumors from P.A-treated mice showed a significant suppression of EGFR phosphorylation (Tyr 1173) and reduction of the cell proliferation marker Ki67. Taken together, our results suggest that P.A is a promising anti-cancer therapeutic candidate for NSCLC. Acknowledgements This work was supported by the Macau Science Technology Development Fund (project code: 021/2013/A1, 005/2014/AMJ &amp; 010/2016/A1). Note: This abstract was not presented at the meeting. Citation Format: Run-Ze Li, Xing Xing Fan, Xiao- Jun Yao, Elaine L. Leung, Liang Liu. Proscillaridin A induces apoptosis and suppresses non-small cell lung cancer tumor growth via calcium-induced DR4 up-regulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1857.
Abstract 13427: Clinical Benefit of American College of Chest Physicians versus European Society of Cardiology Guidelines for Stroke Prophylaxis in Atrial Fibrillation
Authors: Ambar A Andrade, Juan Li, Martha J Radford, David S Nilasena, Brian F Gage
Journal: Circulation (2012)

Background Current guidelines for anticoagulant therapy in patients with atrial fibrillation (AF) conflict with each other. The American College of Chest Physicians (ACCP) recommend no anticoagulan...