tbuckley/cabot-search huggingface dataset:
Electroencephalography-Guided Anesthetic Administration and Postoperative Delirium
Authors: Arpad Zolyomi, Neal S. Gerstein, Timothy R. Petersen
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Blinatumomab is safe and effective in relapsed and MRD-positive B-ALL CD19+ patients: The Bologna Compassionate Program Experience.
Authors: Giovanni Martinelli, Stefania Paolini, Claudio Cerchione, Alessandra Santoro, Valentina Robustelli, Simona Soverini, Caterina De Benedittis, Enrica Imbrogno, Andrea Ghelli Luserna di Rorà, Sarah Parisi, Chiara Sartor, Giovanni Marconi, Silvia Lo Monaco, Maria Chiara Abbenante, Maria Chiara Fontana, Antonella Padella, Anna Ferrari, Giorgia Simonetti, Cristina Papayannidis
Journal: Journal of Clinical Oncology (2019)

e18522 Background: Adult B-ALL patients still have a dismal prognosis, due to a high incidence of relapse even after allogenic SCT. Safety and efficacy of Blinatumomab, anti CD3-CD19 Bite antibody, has been demonstrated both in MRD pos patients and in relapsed/refractory (R/R) setting. To evaluate safety profile and efficacy of Blinatumomab, obtained through a compassionate use, in a cohort of 18 adult patients affected by MRD+ or R/R B-ALL treated at Bologna University. Methods: From March 2015 to December 2017, 18 patients received Blinatumomab at the standard dosage (9 mcg/d x 7 days, 28 mcg/d x 21 days) in 28-days courses. All the patients were hospitalized to receive the 1st course of therapy. The following courses, based on the good safety profile of the compound, were administered in outpatient setting. 18 patients (M/F = 10/8; median age 43, r. 18-73) have been treated. Ph chromosome was detected in 8/18 . 10 were MRD+ (5 Ph pos and 5 Ph neg); E2A-PBX1 and MLL-AF4 rearrangements were found in two patients. 8 patients had a R/R disease (3 Ph pos/5 Ph neg). Median WBC count before starting therapy with Blinatumomab was 5400/mmc (r. 500-76500). All patients had previously received many lines of therapy (median 4, r. 1-7). In 4 cases an alloTMO was already performed, and two patients had received two transplants. 12/18 patients were referred to us by other Institutions. All the patients received at least one course of Blinatumomab. Bone marrow evaluations, including cytogenetics, molecular biology and immunophenotyping analysis were performed at the beginning of every course of therapy in order to assess patients' disease status. MRD evaluation was assessed through BCR-ABL fusion transcript quantitative analysis in Ph pos ALL patients and Ig rearrangment in Ph neg patients. Monitoring of adverse events was periodically performed. 16/18 patients are evaluable for response, at least to one cycle. Results: 9/16 (56%) patients obtained a CR (7/9 MRD+ and 2/7 R/R). In 7/9 (78%) responders patients a molecular CR was reached, (in 6 patients after the first course, in one case after the second one). 5 responders proceeded to alloBMT and are actually alive in CR (median follow-up after transplant 240 days). In terms of toxicity, one patient developed a grade IV neurological event (mental confusion, tremor), which completely resolved after a transient drug withdrawal. Conclusions: Our results confirm the high rate of response and to Blinatumomab in a poor patients' population, and the good management profile of the compound.
Abstract 249: Sigma-1 Receptor Agonist Ameliorates Mitochondrial ATP Production and Apoptosis in Cardiac Myocytes
Authors: Hideaki Tagashira, Norifumi Shioda, Md. Shenuarin Bhuiyan, Kohji Fukunaga
Journal: Circulation Research (2012)

Objective: Selective serotonin reuptake inhibitors (SSRIs) are known to reduce post-myocardial infarction (MI)-induced morbidity and mortality. However, the molecular mechanism underlying SSRI-induced cardioprotection remains unclear. We previous reported that fluvoxamine with high affinity for sigma-1 receptor ameliorates cardiac hypertrophy and dysfunction via sigma-1 receptor stimulation. In non-cardiomyocytes, sigma-1 receptor interacts with IP 3 receptor (IP 3 R), which may promote Ca 2+ transport to mitochondria. We here investigated the role of sigma-1 receptor for sarcoplasmic reticulum (SR)-mitochondrial Ca 2+ signaling in neonatal rat ventricular cardiomyocytes. Methods: Cultured cardiomyocytes were treated with angiotensin II (Ang II) during 72 hr followed by fluvoxamine and/or NE-100 treatment during the last 24 hr. Then, we investigated intracellular localization of sigma-1 receptor and IP 3 R. We also measured phenylephrine (PE)-induced mitochondrial Ca 2+ and cytosolic Ca 2+ mobilization and ATP content in Ang II-treated cardiomyocytes with or without fluvoxamine treatments. Results: Ang II stimulation for 72 hr elicited cardiomyocyte hypertrophy, downregulation of sigma-1 receptor expression and declined PE-induced Ca 2+ mobilization into cytosol and mitochondria. Fluvoxamine treatments restored sigma-1 receptor expression and PE-induced Ca 2+ mobilization into mitochondria. Moreover, fluvoxamine treatment completely restored Ang II-induced apoptosis. We also confirmed in vivo that fluvoxamine treatment rescue transverse aortic constriction-induced cardiac dysfunction and the reduced ATP concentration. Conclusions: These results suggested that fluvoxamine rescue cardiomyocytes from AngII-induced cardiac myocyte apoptosis through enhancement of SR-mitochondria Ca 2+ transport and mitochondrial ATP production via sigma-1 receptor stimulation.
Overexpression mRNA of HMGA2 and WT1 Genes in Whole Blood Samples As Potential Diagnostic Markers in MPN
Authors: Marina Stolyar, Aleksey Gorbenko, Mikhail Mikhalev, Tatiana Olkhovik, Anna Khazieva, Nataliya Belevcova, Kseniya Tabakova, Evgeniy Vasiliev, Igor Olkhovskiy
Journal: Blood (2018)
Abstract 11522: Does Neointimal Pattern Predict Instent Thrombus
Authors: Lei Gao, Stephen Lee, Chong-Jin Kim, Yoshiyasu Minami, Daniel S Ong, Tsunenari Soeda, Harry Lowe, So-Yeon Choi, Amir Lerman, Jay Lee, Hang Lee, Shiro Uemura, Ik-Kyung Jang
Journal: Circulation (2015)

Introduction: Local determinants of instent thrombus formation after drug-eluting stent (DES) implantation have not been systematically investigated. Hypothesis: Certain neointimal patterns assessed by optical coherence tomography (OCT) may represent local surface thrombogenesity after DES implantation. Methods: A total of 208 patients with 262 DES who underwent follow-up OCT examination 11 months after DES implantation were studied. The detailed OCT findings including characteristics of neointima, lumen size, and stent morphology were compared between the group with and without thrombus. Results: Thrombus was identified in 11.5% (24/208) of the patients. Lipid-laden neointima, thin-cap fibroatheroma, heterogeneous neointima, and extra-stent lumen were more frequently detected in the thrombus group compared to the non-thrombus group (Figure). No difference was found in the % of uncovered (4.9±6.7% vs. 4.2±5.4%; p=0.575) or malapposed struts (1.5±2.5% vs. 0.8±2.1%; p=0.116) between the two groups. Minimal lumen cross sectional area was significantly smaller in the thrombus group compared with the non-thrombus group (2.9±1.7mm 2 vs. 4.6±2.0mm 2 ; p&lt;0.001). Conclusions: Neointimal morphology and smaller lumen cross-section area are important factors associated with instent thrombus.
Abstract 14951: Discovery of a Novel Angiogenic Factor TBX20
Authors: Shu Meng, Qilin Gu, Xiaojie Yang, Jie Lv, Iris Owusu, Gianfranco Matrone, Kaifu Chen, Longhou Fang, John Cooke
Journal: Circulation (2017)

Background: T-box 20 (TBX20) is a crucial transcription factor for embryonic development. TBX20 deficiency is associated with congenital heart disease. However, a role of TBX20 in angiogenesis has ...
Abstract 4970: Establishment of a patient-derived platform for preclinical immunooncology studies using autologous tumor and TIL coculture
Authors: Kaede Hinada, Dennis Garland, Dileep Nair, Yong Hu, Thomas Broudy
Journal: Cancer Research (2019)

Abstract The use of tumor infiltrated lymphocytes (TILs) as an adoptive cell transfer therapy to treat cancer has been conducted in clinic trials for more than two decades. TIL therapy in combination with added immunotherapy treatments, such as IL-2 or anti-CTLA4, has further improved clinical response rates. Isolated from a patient’s own tumor specimen, TILs that recognizes tumor-specific known or unknown antigens can be expanded and infused back to tumor-bearing patients to attack autologous cancer cell populations. Despite the progress in clinical research, preclinical and translational models of autologous tumor/TIL coculture have been difficult to establish. This study has established autologous tumor/TIL coculture methods directly from patient tumor specimens. Models were established from BioDuro’s viably cryopreserved tumor &amp; TIL bank, containing more than 100,000 patient biospecimens. Each patient specimen contains a heterogeneous population of cells types, including tumor, TILs and TAFs (tumor associated fibroblasts). These cell populations were expanded under specific growth conditions to then serve as components for the patient-derived coculture systems established. In this study, TILs and monocytes from a cohort of patient tumor specimens (including kidney, melanoma and lung) were analyzed. Leukocytes, T cells, monocytes and B cells were marked with CD45, CD3, CD14, CD20. Patients’ samples were also tested for PD-1 expression levels. The results show significant individual variation on cell subpopulations and PD-1 expression. Established methods were used for expansion of TILs, supporting either CD4 or CD8 phenotypes. Autologous cancer cells were expanded at the same time. TILs and tumor cells were co-cultured and high content fluorescent image cytometry was used to monitor tumor cell killing. This study found that autologous patient-matched TILs showed preferential tumor cell killing compared to patient-unmatched TILs. This response was observed in a dose dependent fashion. In summary, the BioDuro biobank of viable tumor and TIL patient specimens served as a large and powerful immunooncology resource to establish patient-derived autologous tumor/TIL coculture assays. These assays, and the ability to readily study larger populations of cancer patients, provide a powerful in vitro platform to test immunooncology drug candidates. Citation Format: Kaede Hinada, Dennis Garland, Dileep Nair, Yong Hu, Thomas Broudy. Establishment of a patient-derived platform for preclinical immunooncology studies using autologous tumor and TIL coculture [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 4970.
Abstract 3200: Immunotuning CD8+ T cells with BCAT1 inhibition to increase the efficacy of anti-PD-1 therapy and to eradicate moderately immunogenic tumors
Authors: Adonia E. Papathanassiu, Dong-Wook Kim, Kwon-Sik Park, Jeong Hun Ko, Jacques V. Behmoaras
Journal: Cancer Research (2019)

Abstract Activation and differentiation of adaptive and innate immune cells require metabolic reprogramming involving diverse metabolic processes. Understanding these processes affords the opportunity to influence and ultimately re-direct the function and fate of these cells. Here, we present data suggesting that exposure of newly activated human CD8+ T cells to a small molecule inhibitor (ERG245; 50-400 μM) of BCAT1 (the cytosolic isoform of the enzyme responsible for the first step in the catabolism of leucine, isoleucine, and valine) resulted in inhibition of T cell proliferation, inhibition of IFNγ and Granzyme B production, and upregulation of PD-1. The antiproliferative effect, as determined by CFSE dilution, required inhibition of BCAT1 during the first 24 hrs of T cell activation and it was reversible upon early withdrawal of the inhibitor. Early withdrawal of ERG245 reversed the observed immunosuppression, ultimately giving rise to CD8+ T cells with higher proliferative capacity and increased cytotoxicity compared to untreated control cells. Exposure of CD8+ T cells to ERG245 resulted in a distinct metabolic phenotype including reduced concentrations of α-ketoglutaric acid (αKG), and lower levels of trimethylation of the lysine 4 (K4) and lysine 27 (K27) sites of histone 3 (H3), which implies that BCAT1 inhibition has epigenetic effects on human CD8+ T cells by modulating αKG-dependent histone demethylases. Similar observations were made with CD8+ T cells, isolated from the spleens of Bcat1 KO mice. In vivo, ERG245 (given at 5 mg/kg ip, bid at days 0, 1 and 2 of treatment), dramatically increased the efficacy of an anti-PD-1 antibody (clone RMP1-14; given at 10 mg/kg at days 0, 4, 7, and 11 of treatment) in the CT26 colon cancer model. Specifically, the combination of ERG245 and anti-PD-1 eradicated established tumors within a week of treatment initiation (cure rate of &amp;gt;80%), whereas the monotherapies (ERG245 or anti-PD-1 alone) did not improve the disease outcome. The data suggest that the temporal exposure of moderately immunogenic tumors to BCAT1 inhibition sensitizes the tumors to checkpoint inhibition. Citation Format: Adonia E. Papathanassiu, Dong-Wook Kim, Kwon-Sik Park, Jeong Hun Ko, Jacques V. Behmoaras. Immunotuning CD8+ T cells with BCAT1 inhibition to increase the efficacy of anti-PD-1 therapy and to eradicate moderately immunogenic tumors [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 3200.
Molecular fingerprints and mechanisms of chemoresistance in ovarian cancer
Authors: John Quackenbush, Jian-Bing Fan, Michelle Hirsch, Kristina Holton, Renee Rubio, Craig April, Jing Chen, Eliza Wickham-Garcia, Joyce Liu, Aedin Culhane, Ronny Drapkin, Ursula Matulonis
Journal: Cancer Research (2008)

4128  Advanced ovarian cancer (stages III and IV) accounts for more than 75% of the approximately 23,000 new cases of epithelial ovarian cancer per year in the United States. Over 16,000 deaths per year occur, making this cancer the most lethal gynecologic malignancy. Although ovarian cancer is notable for its initial chemotherapy sensitivity using combination platinum and taxane chemotherapy following debulking surgery (greater than 75% response rates), the vast majority of these women (75%-80%) relapse within 12 to 24 months after diagnosis and die of a progressively chemotherapy-resistant tumor. Despite significant investment, no major improvements in survival have been achieved in more than 10 years.  Recently, we embarked on a large-scale project to develop a detailed understanding of the molecular events associated with chemotherapy resistance in ovarian cancer. Using more than 250 well-annotated formalin-fixed, paraffin embedded (FFPE) samples, we have generated expression profiles for 12,000 mRNA and 735 miRNAs using the Illumina DASL® platform. The resulting de-identified data have been collected with the relevant clinical information in a web-accessible relational database and subjected to rigorous statistical and computational analysis to identify expression profiles predictive of outcome. Categorical functional analysis of the resulting gene lists has identified a number of novel mechanisms associated with chemoresistance. Application of a recently-developed seeded Bayesian Network algorithm has allowed construction of predictive models that provide testable hypotheses regarding mechanism and potential therapeutic intervention. Results are being validated using qRT-PCR and tissue microarray analysis and network models are being refined using an iterative strategy using RNA interference, expression profiling, and computational analysis.  We will present an overview of the laboratory and analytical methodologies we have developed and describe our findings relevant to overcoming chemoresistance.
Abstract 2309: Chimeric antigen receptor T-cell therapy targeting glypican-1 in pancreatic cancer
Authors: Nan Li, Dan Li, Hua Ren, Madeline Torres, Mitchell Ho
Journal: Cancer Research (2019)

Abstract Pancreatic cancer is the fourth most common cause of death from cancer in the US, with a 5-year overall survival of 8.5%. While immunotherapy with chimeric antigen receptor (CAR) T cells has shown promise in certain hematological malignancies, their efficacy for solid tumors including pancreatic cancer remains elusive. Thus, laboratory research is urgently needed to identify and validate a new target of CAR T-cell therapy for patients with pancreatic cancer. In this study, we made CAR T cells that recognize glypican-1 (GPC1), a cell surface heparan sulfate proteoglycan protein that is overexpressed in pancreatic cancer. We isolated two GPC1-specific antibodies; the mouse monoclonal antibody HM2 that binds the C-lobe of GPC1 close to the cell surface, and the camel single domain antibody D4 that recognizes a conformational epitope in the protein core of GPC1. The transduction efficiencies of CAR (HM2) and CAR (D4) in primary T cells were 86% and 58%, respectively. GPC1-overexpressing KLM1 cells (2B9) and GPC1-overexpressing A431 cells (H8) were efficiently lysed by both CAR T cells in dose-dependent manners. By contrast, minimal cell lysis was observed in GPC1-negative cell line A431. In the presence of GPC1-positive tumor cells, greater amount of TNF-α, IFN-γ and IL-2 were produced by GPC1-specific CAR T cells than mock-transduced T cells. Although both CAR T cells showed similar cytolytic activity in vitro, CAR (D4) T cells induced 2-4 times more cytokines than CAR (HM2) T cells when co-cultured with GPC1-postive tumor cells. Notably, both GPC1-targeted CAR T cells demonstrated potent antitumor efficacy in a peritoneal dissemination xenograft mouse model. Our findings indicate that GPC1-targeted CAR T cell therapy could be a new approach for treating pancreatic cancer. Citation Format: Nan Li, Dan Li, Hua Ren, Madeline Torres, Mitchell Ho. Chimeric antigen receptor T-cell therapy targeting glypican-1 in pancreatic 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 2309.
Treatment of relapsed oesophagogastric adenocarcinoma after perioperative chemotherapy and surgery
Authors: M. Davidson, C. Butler, O. Butters, C. Fong, F. Turkes, C. Cafferkey, K. Kouvelakis, D. Cunningham, D. Watkins, S. Rao, N. Starling, I. Chau
Journal: Annals of Oncology (2019)
Abstract 2962: Targeting BCL2 as a therapeutic strategy in neuroendocrine prostate cancer
Authors: Alexandra N. Corella, Jared M. Lucas, Arja Kaipainen, Ilsa M. Coleman, Colm Morrissey, Eva Corey, Paul Nghiem, David MacPherson, Peter S. Nelson
Journal: Cancer Research (2019)

Abstract Small-cell neuroendocrine prostate carcinoma (SC/NEPC) is an aggressive subtype of prostate cancer (PC) with poor response to conventional therapies and no approved targeted therapies. The molecular mechanisms that drive the growth and survival of these tumors are poorly understood due to disease rarity and a lack of model systems for the subtype. SC/NEPC shares defining characteristics with other aggressive small-cell neuroendocrine tumors, such as “small-blue round cell” morphology and expression of chromogranin A. In this study, we compare whole transcriptome RNA-sequencing data from metastatic PCs and two additional SC/NE tumor types, small cell lung cancer (SCLC) and Merkel Cell carcinoma (MCC). By differential expression analysis of each neuroendocrine tumor type to Androgen Receptor-responsive Prostate Cancer (AR-PC), we identify 4,300 genes exhibiting shared expression patterns in multiple neuroendocrine tumor types. Among these “pan-neuroendocrine” genes are known and proposed drivers of the neuroendocrine transcriptional program including MYCN (p=8.7E-07, upregulated in SC/NEPC over AR-PC) and potential novel drivers of the neuroendocrine phenotype in PC such as MYCL (p=3.5E-05, upregulated in SC/NEPC over AR-PC). We also identify conserved expression patterns of druggable targets including BCL2 which has previously been reported as highly expressed in subsets of SCLC and MCC, but not SC/NEPC (p=1.24E-05, upregulated in SC/NEPC over AR-PC). We then analyzed a panel of cell lines and novel PDX models, which further confirm that the BCL2 protein is highly expressed specifically in the SC/NEPC phenotype. We determined that SC/NEPC cell lines and PDX models are sensitive to BCL2 family member inhibitors targeting BCL2, BCLXL, BCLW, including, ABT263, ABT199 and ABT737, at sub-micromolar concentrations, whereas models of ARPC were resistant. These inhibitors lead to apoptotic cell death in SC/NEPC. Collectively, our data suggests that BCL2 inhibition may present a novel targeted approach for SC/NEPC that warrants further evaluation. Citation Format: Alexandra N. Corella, Jared M. Lucas, Arja Kaipainen, Ilsa M. Coleman, Colm Morrissey, Eva Corey, Paul Nghiem, David MacPherson, Peter S. Nelson. Targeting BCL2 as a therapeutic strategy in neuroendocrine prostate 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 2962.