tbuckley/cabot-search huggingface dataset:
Abstract 766: Mutual negative regulation of EZH2 and miR-4448 for tumor progression via epithelial mesenchymal transition in small cell lung cancer
Authors: Nobuyuki Koyama, Yuichi Ishikawa, Yuki Iwai, Kazutetsu Aoshiba, Hiroyuki Nakamura, Koichi Hagiwara
Journal: Cancer Research (2019)

Abstract Enhancer of zeste homolog 2 (EZH2) is a catalytic component of polycomb repressive complexes, promotes tumor progression and metastasis. Expression levels of EZH2 are associated with clinical outcomes in a variety of tumors. High expression levels of EZH2 have been reported in cell lines and tissues of small cell lung cancer (SCLC), which is characterized by its invasiveness and metastatic potentials. Epithelial-mesenchymal transition (EMT) is well recognized to contribute to aggressiveness of SCLC, and microRNA (miRNA) is known to be associated with both EMT and the biological characteristics of SCLC. The aim of this study was to identify a novel miRNA defining EZH2-assciated EMT and tumor aggressiveness in SCLC. Immunohistochemistry and quantitative PCR showed that EZH2 expressions levels were decreased in three types of SCLC cell lines and tumor tissues from 34 patients with SCLC. Small interfering RNA (siRNA) against EZH2 suppressed its expression and EMT in SBC3 and SBC5 cell lines, both of which had high EZH2 expression levels as SCLC cell lines. Comprehensive miRNA expression analysis was used to compare changes of miRNA expression between EZH2 siRNA-transfected cells and mock-transfected cells. As a result, miR-4448 expression was significantly decreased in SBC3 and SBC5 cells transfected with EZH2 siRNA. Cell growth assay and cell invasion assay revealed that overexpression of miR-4448 inhibited cellular proliferation and invasion potential. Furthermore, we confirmed that overexpression of miR-4448 abrogated EMT and decreased EZH2 expression. In conclusion, EZH2 and miR-4448 mutually suppressed these expressions and functions, which was associated with tumor progression via EMT in SCLC. The findings of this study suggest that miR-4448 may play a crucial role in the biological characteristics of SCLC. Citation Format: Nobuyuki Koyama, Yuichi Ishikawa, Yuki Iwai, Kazutetsu Aoshiba, Hiroyuki Nakamura, Koichi Hagiwara. Mutual negative regulation of EZH2 and miR-4448 for tumor progression via epithelial mesenchymal transition in small cell lung cancer [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 766.
Abstract 1032: Establishing an <i>in vitro</i> model of lipopolysaccharide-induced tumorospheres formation of prostate epithelial cells for drug screening
Authors: Jiajia Jiang, Xueqi Lian, Sijie Tang, Xiaohua Li
Journal: Cancer Research (2019)

Abstract Tumorospheres forming assay not only was utilized to enrich cancer stem cell from bulk cancer cells, also was widely used to analyze the ability of clonogenic growth and self-renewal capability of cancer stem cells. Meanwhile, chronic inflammation-induced epithelial transformation has been documented in a broad range of cells. However, the effect of chronic inflammatory agent on tumorosphere formation has never been tested. In current study, the classic pro-inflammatory agent lipopolysaccharide was utilized to establish an in vitro model through inducing prostate tumoroshpere formation. Then, trichostatin A, a panel inhibitor of histone deacetylases, was tested in this model for its anti-tumor effect. The results showed that treatment with lipopolysaccharide stimulated prostate cancer DU145 and PC3 cells undergoing migration and invasion with decreased the ratio of CK8 and CK18 versus vimentin. It also induced tumorospheres formation in suspension culture with increased a panel of tumor stem cell markers transcription (e.g. CD44, α-intergrin, nestin etc) and promoted phosphorylation of Stat3 (p-Stat3) and pro-oncogene c-Myc expression in vitro. Treatment with trichostatin A showed to restrain the above lipopolysaccharide-induced EMT and tumorosphere formation with decreasing the level of p-Stat3, p-Erk, p-c-jun, c-Myc, CD44 and SOX-2. Finally, blocking Stat3 signaling pathway by treatment with trichostatin A and/or small molecule compound Stattic, an inhibitor of p-Stat3, abrogated LPS-induced cancer stem-like tumorosphere formation. Taken together, our data demonstrated that lipopolysaccharide induced cancer stem-like tumorospheres formation successfully, which could be served as a simple and easy handling in vitro model for anti-tumor drug screening. Citation Format: Jiajia Jiang, Xueqi Lian, Sijie Tang, Xiaohua Li. Establishing an in vitro model of lipopolysaccharide-induced tumorospheres formation of prostate epithelial cells for drug screening [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 1032.
Abstract 16628: Effect of Hospital Procedure Volume on In-Hospital Mortality After Left Ventricular Assist Device (LVAD) Implantation in Advanced Heart Failure Patients From 1998 to 2010: An Analysis of 10,251 Procedures
Authors: Neeraj Shah, Ankit Chothani, Shilpkumar K Arora, Kathan Mehta, Nileshkumar J Patel, Ghanshyambhai T Savani, Nilay Patel, Peeyush Grover, Vikas Singh, Ankit Rathod, Abhishek Deshmukh, Apurva O Badheka, Mark Hofmeyer
Journal: Circulation (2013)

Background: LVAD is used either as destination therapy (DT) or bridge to transplant (BTT) in patients with advanced heart failure. We aim to examine if any relation exists between hospital volume a...
Antitumor activity of a novel, human anti-epidermal growth factor receptor (EGFR) monoclonal antibody (IMC-11F8) in human tumor xenograft models
Authors: Marie Prewett, James R. Tonra, Bassi Rajiv, Andrea T. Hooper, Genevieve Makhoul, Bridget Finnerty, Larry Witte, Peter Bohlen, Zhenping Zhu, Daniel J. Hicklin
Journal: Cancer Research (2004)

5353  Molecular inhibition of epidermal growth factor receptor (EGFR) function is a promising approach to cancer therapy. In this report, we describe the in vivo activity of a novel, high affinity human anti-EGFR monoclonal antibody, designated IMC-11F8. Antitumor activity of IMC-11F8 was evaluated in models of established (0.20 cm3) epidermoid (A431), pancreatic (BxPC-3) or colon (HT-29 and DLD-1) human tumor xenografts in athymic mice. Dose-dependent inhibition of tumor growth in all models was observed in mice treated with IMC-11F8 (1mg or 0.3mg; 3x/week) with T/C values ranged from 3% to 17% for the 1mg dose and from 38% to 81% for the 0.3mg dose. Histological examination of tumor xenografts demonstrated a significant decrease in the neoplastic cell compartment compared to controls. Combination therapy experiments were performed in colon xenograft models where established DLD-1, GEO, or HT-29 tumors were treated with IMC-11F8, irinotecan (100mg/kg; q7dx5), or the combination. Treatment with combination therapy significantly inhibited the growth of these tumors compared to IMC-11F8 or CPT-11 therapy alone. Combination therapy with the high dose of IMC-11F8 and CPT-11 resulted in synergistic anti-tumor effect in all three tumor models with T/C% values of 8%, 3%, and 10% for DLD-1, GEO and HT-29, respectively. Combination therapy produced tumor regressions in 50% of the DLD-1 and HT-29 animals and in 90% of the GEO tumors. Histological examination of residual tumors after combination treatment showed an increase in pyknotic nuclei and a decrease in mitotic figures; this resulted in a substantial decrease in viable tumor compartment with near elimination of neoplastic cells. The present study shows that IMC-11F8 may be an effective therapy in the treatment of EGFR-positive tumors and warrants clinical evaluation of this agent.
Abstract 3540: A complete solution for high throughput single cell targeted multiomic DNA and RNA sequencing for cancer research
Authors: Dalia Dhingra, Kaustubh Gokhale, Nianzhen Li, Pedro Mendez, Shu Wang, Manimozhi Manivannan, Adam Sciambi, Keith Jones, Charlie Silver, Dennis Eastburn, David Ruff
Journal: Cancer Research (2019)

Abstract Recent advancements in single cell analysis technologies are now able to provide insights into genomic DNA content, RNA expression and protein surface markers. In bulk assays, the effect of genetic variation on gene expression would be masked by the heterogeneity inherent in tumor cells. Additionally, for cancer immunotherapy studies that rely on gene editing, single cell resolution is necessary to minimize possible off target effects. However, the ability to simultaneously interrogate multiple intracellular analytes, such as genomic DNA and RNA, have proved difficult to implement in a high throughput single cell workflow. We report the development of a complete solution that enables both targeted genomic DNA and RNA sequencing from individual cells. This workflow relies on the Tapestri microfluidic droplet platform, where up to 20,000 cells can be sequenced in each run. Leveraging proprietary cell barcoding, novel primer design strategies and enzymatic manipulation of cellular contents, DNA and RNA multiplex targeted sequencing panels provide for independent barcoded sequence information from both overlapping mRNA and corresponding genomic DNA regions. In addition, amplification primers can be designed to target separate gDNA and non-overlapping RNA transcript. Sequencing is followed by an integrated analysis solution that assigns the reads from both the gDNA and RNA to each cell. Feasibility of the targeted nucleic acid workflow has been shown with inputs from mixed cancer cell lines. A targeted sequencing panel with overlapping mRNA and gDNA regions was designed covering oncogenes, tumor suppressor genes, and known fusions. Expected SNVs and indels were detected and gene expression measured for thousands of cells per run with high cell recovery. This complete solution for single cell multiomics on the Tapestri platform has the power to quantitatively and unambiguously link genotypic and phenotypic data, giving insight into cancer progression. Citation Format: Dalia Dhingra, Kaustubh Gokhale, Nianzhen Li, Pedro Mendez, Shu Wang, Manimozhi Manivannan, Adam Sciambi, Keith Jones, Charlie Silver, Dennis Eastburn, David Ruff. A complete solution for high throughput single cell targeted multiomic DNA and RNA sequencing for cancer research [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 3540.
Nilotinib in Combination with Pegylated Interferon Alfa-2b for CP-CML Leads to High Molecular Response Rates: Interim Results of the Pinnacle Study
Authors: David Yeung, Andrew Grigg, Naranie Shanmuganathan, Ilona Cunningham, Jake Shortt, Philip Rowling, John Reynolds, Rachel Cushion, Rosemary Harrap, David M Ross, David Kipp, Anthony K Mills, Christopher K Arthur, Anthony P Schwarer, Kathryn Jackson, Nicholas Viiala, Robert Weinkove, Agnes S. M. Yong, Deborah L White, Susan Branford, Timothy P. Hughes
Journal: Blood (2017)
Long-Term Outcomes of Lenalidomide and Rituximab in Rituximab-Resistant Patients with Indolent B Cell and Mantle Cell Lymphomas
Authors: Elise A. Chong, Ellen Napier, Jakub Svoboda, Sunita Dwivedy Nasta, Anthony R. Mato, Daniel J. Landsburg, Stephen J. Schuster
Journal: Blood (2017)
Altered neural activity in brain cough suppression networks in cigarette smokers
Authors: Ayaka Ando, Stuart B. Mazzone, Michael J. Farrell
Journal: European Respiratory Journal (2019)

Cough is important for airway defence, and studies in healthy animals and humans have revealed multiple brain networks intimately involved in the perception of airway irritation, cough induction and cough suppression. Changes in cough sensitivity and/or the ability to suppress cough accompany pulmonary pathologies, suggesting a level of plasticity is possible in these central neural circuits. However, little is known about how persistent inputs from the lung might modify the brain processes regulating cough. In the present study, we used human functional brain imaging to investigate the central neural responses that accompany an altered cough sensitivity in cigarette smokers. In nonsmokers, inhalation of the airway irritant capsaicin induced a transient urge-to-cough associated with the activation of a distributed brain network that included sensory, prefrontal and motor cortical regions. Cigarette smokers demonstrated significantly higher thresholds for capsaicin-induced urge-to-cough, consistent with a reduced sensitivity to airway irritation. Intriguingly, this was accompanied by increased activation in brain regions known to be involved in both cough sensory processing (primary sensorimotor cortex) and cough suppression (dorsolateral prefrontal cortex and the midbrain nucleus cuneiformis). Activations in the prefrontal cortex were highest among participants with the least severe smoking behaviour, whereas those in the midbrain correlated with more severe smoking behaviour. These outcomes suggest that smoking-induced sensitisation of central cough neural circuits is offset by concurrently enhanced central suppression. Furthermore, central suppression mechanisms may evolve with the severity of smoke exposure, changing from initial prefrontal inhibition to more primitive midbrain processes as exposure increases.
Avoiding General Anesthesia in Treating Port-Wine Stains in Infants to Avoid Neurotoxic Events—Reply
Authors: Roy G. Geronemus, Hana Jeon, Leonard J. Bernstein
Journal: JAMA Dermatology (2019)

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Evaluation of variables that may impact the use of Oncotype DX testing.
Authors: Stephen Szabo, James W. Gilmore, Sally Haislip, Robert Hassell, Joseph Cooper, Steve Richardson, Meghan Fitzgerald, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2012)

e11002 Background: Cardinal Health Specialty Solutions (CHSS) partners with payers to manage clinical care pathways in oncology and rheumatology. Observations from one such pathway with CareFirst BlueCross Blue Shield revealed that in patients with estrogen receptor-positive early-stage breast cancer (ESBC), there was an underuse of Oncotype DX testing. To better understand physician behavior as it relates to Oncotype DX testing, CHSS examined patterns of Oncotype DX use in a large private practice oncology group with a robust electronic medical record (EMR), Georgia Cancer Specialists (GCS). We aimed to determine the variables that most impacted the use of Oncotype DX testing. Methods: Using the GCS EMR from 2009 to 2011, we retrospectively identified patients diagnosed with ESBC who were eligible for Oncotype DX testing (stage I-II, node-negative, estrogen receptor-positive, HER2-negative). The use of Oncotype DX testing was analyzed by patient age, tumor size, tumor grade, and physician prescribing patterns. Results: Of the 1908 patients identified with ESBC, 788 were eligible for Oncotype DX testing and 288 (37%) underwent testing. In an analysis by age, Oncotype DX was utilized in 34% of patients ≤ 45 years, 49% in patients 46-55 years, 37% in patients 56-65 years, 34% in patients 66-75 years, and 13% in patients &gt; 75 years old. Oncotype DX use was 37% and 36% in patients with tumor sizes &lt;2 cm and 2-5 cm, respectively; and, 45%, 43%, and 67% in patients with grade 1, 2, or 3 tumors, respectively. Of the 41 physicians who were evaluated, 10 (24%) used Oncotype DX &lt;15% of the time, 13 (32%) used Oncotype DX 15-40%, 10 (24%) used ODX 41-60%, and 8 (20%) used Oncotype DX &gt; 60% of the time. There were no significant differences in patterns of chemotherapy use. Conclusions: Based on this analysis, eligible patients with ESBC between 46-55 years of age, with small and intermediate sized tumors (&lt;2-5 cm), and with grade 3 tumors were most likely to undergo Oncotype DX testing. Although some trends in use were observed with specific tumor characteristics, physician behavior (choice) was the most significant variable in Oncotype DX testing.
Evidence for Dissociable Linkage of Dimensions of Psychopathology to Brain Structure in Youths
Authors: Antonia N. Kaczkurkin, Sophia Seonyeong Park, Aristeidis Sotiras, Tyler M. Moore, Monica E. Calkins, Matthew Cieslak, Adon F.G. Rosen, Rastko Ciric, Cedric Huchuan Xia, Zaixu Cui, Anup Sharma, Daniel H. Wolf, Kosha Ruparel, Daniel S. Pine, Russell T. Shinohara, David R. Roalf, Ruben C. Gur, Christos Davatzikos, Raquel E. Gur, Theodore D. Satterthwaite
Journal: American Journal of Psychiatry (2019)

Objective: High comorbidity among psychiatric disorders suggests that they may share underlying neurobiological deficits. Abnormalities in cortical thickness and volume have been demonstrated in clinical samples of adults, but less is known when these structural differences emerge in youths. The purpose of this study was to examine the association between dimensions of psychopathology and brain structure. Methods: The authors studied 1,394 youths who underwent brain imaging as part of the Philadelphia Neurodevelopmental Cohort. Dimensions of psychopathology were constructed using a bifactor model of symptoms. Cortical thickness and volume were quantified using high-resolution 3-T MRI. Structural covariance networks were derived using nonnegative matrix factorization and analyzed using generalized additive models with penalized splines to capture both linear and nonlinear age-related effects. Results: Fear symptoms were associated with reduced cortical thickness in most networks, and overall psychopathology was associated with globally reduced gray matter volume across all networks. Structural covariance networks predicted psychopathology symptoms above and beyond demographic characteristics and cognitive performance. Conclusions: The results suggest a dissociable relationship whereby fear is most strongly linked to reduced cortical thickness and overall psychopathology is most strongly linked to global reductions in gray matter volume. Such results have implications for understanding how abnormalities of brain development may be associated with divergent dimensions of psychopathology.
Abstract 3676: Novel tumor suppressive role of Peptidylarginine deiminase IV involving cancer stem cell regulation in breast cancer models
Authors: Humberto J. Ochoa, Nellie Moshkovich, Binwu Tang, Howard H. Yang, Maxwell P. Lee, Lalage M. Wakefield
Journal: Cancer Research (2019)

Abstract Breast cancer accounts for &amp;gt;500,000 deaths annually worldwide. Despite therapeutic advances, treated patients often relapse with metastases. Emerging research indicates that relapse may be driven by a subpopulation of tumor cells termed cancer stem cells (CSCs), that are uniquely capable of self-renewal and have enhanced drug resistance. Understanding the properties of these CSCs is critical for development of more effective therapies. Peptidyl arginine deiminase 4 (PADI4) is an enzyme that catalyzes deimination of arginine to citrulline. Citrullination of histones modulates expression of key stem cell transcription factors in embryonic stem cells (Christophorou, et al., 2014, Nature 507:104), so we hypothesized that PADI4 could be involved in CSC regulation. We showed that PADI4 mRNA and protein are expressed at varying levels across a panel of breast cancer cell lines, and we knocked down PADI4 in two high expressing lines, MCF10Ca1h and MDAMB231-LM2. PADI4 knockdown did not alter tumor cell proliferation in vitro, but it enhanced migration and invasion and increased cell survival. Importantly, PADI4 knockdown increased clonogenicity and enhanced tumorsphere formation, suggesting that it specifically increases the CSC population. In vivo studies showed higher tumor initiation efficiency following PADI4 knockdown, and increased lung metastasis. PADI4 is predicted to have multiple isoforms with unknown biological activity that complicate PADI4 expression-based analysis in patient data sets. We circumvented this issue by pharmacologically inhibiting PADI4 in MCF10Ca1h to generate a transcriptomic signature reflecting PADI4 gene activity. This PADI4 gene activity signature was shown to correlate with lower tumor grade and better disease outcome in transcriptomic datasets from human ER+ breast cancers. In conclusion, our findings suggest that PADI4 functions as a tumor suppressor in breast cancer, in part through effects on the CSC. Citation Format: Humberto J. Ochoa, Nellie Moshkovich, Binwu Tang, Howard H. Yang, Maxwell P. Lee, Lalage M. Wakefield. Novel tumor suppressive role of Peptidylarginine deiminase IV involving cancer stem cell regulation in breast cancer models [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 3676.
Durability of complete response after blinatumomab therapy for refractory/relapsed aggressive B-cell non-Hodgkin lymphoma.
Authors: Andreas Viardot, Georg Hess, Ralf C. Bargou, Nicholas Morley, Giuseppe Gritti, Karim Iskander, David Cohan, Alicia Zhang, Janet Franklin, Luke Coyle
Journal: Journal of Clinical Oncology (2019)

e19041 Background: Achieving durable response in patients (pts) with relapsed/refractory (R/R) aggressive B-cell lymphoma (B-NHL) is challenging. Blinatumomab, a bispecific T-cell engager (BiTE) immunotherapy targeting CD19-expressing cancer cells, has shown promising efficacy in pts with R/R aggressive B-NHL. We report the durability of complete response (DOCR) in pts treated with blinatumomab. Methods: The DOCR in pts with R/R aggressive B-NHL responding to blinatumomab was assessed using data from two phase 2 studies (study 1 [N = 25], NCT01741792; study 2 [N = 41], NCT02910063) in pts with R/R aggressive B-NHL. CR was assessed using Cheson (study 1) and Lugano (study 2) criteria. Time-to-event variables were analyzed using the Kaplan-Meier (KM) method. Results: Baseline pt characteristics in the pooled analysis were: median age 59 years (range, 4177); 54% men; 54% treatment refractory; median 2 lines of prior therapy (range, 17); and 15% with prior autologous hematopoietic stem cell transplant. Of 25 pts treated with blinatumomab in study 1, 4 (16%) evaluable pts achieved CR. Of 41 pts treated with blinatumomab in study 2, 9 (22%) achieved CR. Median DOCR was not reached (Table). At a median follow-up of 9.1 months in the pooled analysis, 3 pts (23%) had relapsed (study 1, n = 2 [50%]; study 2, n = 1 [11%]). At 12 and 18 months, the KM probability of maintaining CR in the pooled analysis was 53.0% (95% confidence interval [CI], 8.5, 85.0). Conclusions: For pts with R/R aggressive B-NHL who received blinatumomab, a durable response is possible. Longer-term follow up is needed to fully characterize the DOCR to blinatumomab. Clinical trial information: NCT01741792; NCT02910063. [Table: see text]