tbuckley/cabot-search huggingface dataset:
Sintilimab for relapsed/refractory (r/r) extranodal NK/T-cell lymphoma (ENKTL): A multicenter, single-arm, phase 2 trial (ORIENT-4).
Authors: Rong Tao, Lei Fan, Yongping Song, Yu Hu, Wei Zhang, Yafei Wang, Linxinyu Xu, Hui Zhou, Jianyong Li
Journal: Journal of Clinical Oncology (2019)

7504 Background: ENKTL account for more than 20% of the peripheral T-cell lymphoma in Asia. Patients with r/r ENKTL have a poor prognosis after failing an L-asparaginase based regimen, and the median overall survival is less than 6 months. The overexpression of PD-L1 induced by EBV infection is a potential mechanism for ENKTL to avert immune surveillance, and recent studies of PD-1 antibodies in pts with r/r ENKTL have demonstrated potential efficacy. Sintilimab, a fully human anti-PD-1 monoclonal antibody, has a safety profile consistent with other approved PD-1 antibodies and was approved for r/r classical Hodgkin lymphoma in China in 2018. This multicenter, single-arm, phase 2 study aims to validate the efficacy and safety of sintilimab monotherapy in patients with r/r ENKTL in China. Methods: Patients with pathologically confirmed r/r ENKTL were enrolled. Sintilimab was given 200 mg IV Q3W, until PD, death, unacceptable toxicity, or withdrawal from the study. Treatment beyond PD is allowed. Tumor response evaluation was performed by both PET-CT and CT/MRI with contrast. The primary endpoint was objective response rate based on LUGANO 2014 criteria. Data cut-off date for this analysis was Feb 2, 2019. Results: From Aug 31, 2017 to Feb 7, 2018, a total of 28 patients were enrolled: 60.7% male and the median age was 37 (range: 19–65) yr. Sixty-eight percent of patients were stage IV and 89.3% were ECOG PS ≥ 1. All patients had failed an L-asparaginase based regimen, the median lines of previous therapy were 3 (range: 1–13), 78.6% patients received prior radiotherapy and 7.1% had failed HSCT. Median duration of therapy was 14.04 (range: 1.4–17.3) months and 19 patients are still receiving sintilimab. Sixty-eight percent (19/28, 95%CI: 47.6%–84.1%) of patients achieved response (CR+PR), including 4 pts who experienced PD prior to having a response. DCR was 85.7%, including 5 pts who experienced PD before SD or response. The 1-year OS rate was 82.1% and the median OS has not been reached. Most TRAEs were G1–2 (67.9%) and no patients discontinued treatment due to AEs. The most common TRAE was decreased lymphocyte count (46.4%) and 84.6% were grade 1–2. SAEs occurred in 21.4% of patients and none were related to sintilimab. No patients died from AEs. Conclusions: Sintilimab is effective and well tolerated in r/r ENKTL and could be a promising treatment option for these patients. Early disease progression observed by PET scan in this study could be pseudoprogression as it did not correlate with poor outcome, which warrants further investigation. Clinical trial information: NCT03228836.
Abstract 1170: Designing a biomarker-based bedside tool-kit for the clinical evaluation of bladder cancer
Authors: Isha R. Dabke, Richard Pearce, Georgios Kallifatidis, Balakrishna Lokeshwar
Journal: Cancer Research (2019)

Abstract Cancer of the urinary bladder (UBC) ranks second in incidence and mortality among the genitourinary cancers causing over 16,000 deaths annually. Currently, the precise diagnosis of bladder cancer involves cystoscopy and cytology, both expensive and painful procedures. Morphologically, malignancies of the bladder can be divided into two subtypes: luminal and basal, which express distinct cytokeratin and stem cell markers and have differing sensitivities to therapy. Although diagnosis based on molecular signatures has the potential to be effective, a verification of their expression in strictly compartmentalized epithelial subtypes is not presently available. The implications of this project are the formation of a bedside tool-kit based on prognostic stem cell biomarkers that can be used following biopsy to efficiently evaluate cancer subtype and provide a preliminary diagnosis. Towards that goal, we analyzed mRNA expression profiles in five established bladder cancer cell lines (RT-4, 5637, T24, HT-1376, 253J), ranging from a grade I (RT-4) to a grade IV cancer cell line (253J). Based on existing literature, these cell lines were classified into either the luminal or basal subtype of bladder cancer. Through RT-PCR and Western Blot studies, genomic expression levels of eleven biomarkers (luminal: UPK, GATA-3, RAB-25, E-Cadherin; and basal: CK-6, p63, CD44S, CD44V, CyclinB1, EGFR, CD49) were analyzed in these cell lines. Cell viability following exposure to two chemotherapy drugs: Gemcitabine and Cisplatin, commonly used to treat bladder cancer, were assayed by colorimetric and clonogenic colony-forming assays. Literature states that though basal cancers are more aggressive, they are paradoxically more sensitive to chemotherapy compared to luminal UBC. Less aggressive/luminal UBC cell lines showed higher mRNA levels for luminal biomarkers, and expressed GATA-3 100% of the time. The more invasive/basal cell lines showed only a slight upregulation of basal biomarkers, but expressed CD44S 100% of the time. Furthermore, MTT Assays showed a significant toxic effect of Gemcitabine on basal cell lines earlier (t=24 hr vs 48/72 hr) than luminal cell lines. However, Cisplatin did not show a significant difference in luminal vs. basal UBC suggesting that the two subtypes of UBC have similar sensitivity to Cisplatin. The study presented here suggests that a PCR-based, biomarker toolkit can aid in an efficient classification of bladder cancers at the bedside, and treatment can be personalized based on the UBC subtype. Citation Format: Isha R. Dabke, Richard Pearce, Georgios Kallifatidis, Balakrishna Lokeshwar. Designing a biomarker-based bedside tool-kit for the clinical evaluation of bladder 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 1170.
Abstract 12215: Liposome-Encapsulated Hemoglobin, Artificial O2 Carrier, Preserves VO2 and Protects Myocardium after Myocardial Ischemia/Reperfusion in the Rat
Authors: Akira T Kawaguchi, Mariko Yamano
Journal: Circulation (2011)

Background: We tested the hypothesis that liposome-encapsulated hemoglobin (LEH) increases blood O2 content and maintains VO2 even at low cardiac output (LOS), simultaneously preserving hemodynamic...
Abstract 1249: The role of PRMT5 in MYC-driven medulloblastoma
Authors: Nagendra K. Chaturvedi, Varun Kesherwani, Matthew J. Kling, Sutapa Ray, Timothy R. McGuire, Shantaram S. Joshi, J. Graham Sharp, Don W. Coulter
Journal: Cancer Research (2019)

Abstract Medulloblastoma (MB) is the most common pediatric brain tumor, accounting for about 20% of all brain tumors in children. Children with Group 3 MB (aberrant MYC) show the worst prognosis, with &amp;lt;50% survival. Recently, the role and association of protein arginine methyl transferase (PRMT) 5 have been closely associated with aberrant MYC function in various cancers including other brain tumors such as glioblastoma. However, the role of PRMT5 and its association with MYC in MB have not been explored. Here we provide preliminary data indicating PRMT5 as a novel regulator of MYC and implicating PRMT5 as a potential therapeutic target in MYC-driven MB. Using cell lines, our results showed PRMT5 overexpression in MYC-driven MB compared to non-MYC MB. The results from co-immunoprecipitation experiment in MYC-driven MB cells demonstrated that MYC physically associates with PRMT5 by direct protein-protein interaction. In addition, cycloheximide chase experiment showed that PRMT5 regulates MYC stability. Knockdown of PRMT5 using siRNA in MYC-driven MB cells significantly decreased cell growth and MYC expression. We also tested the therapeutic potential of targeting PRMT5 against MB cell lines using a small molecule inhibitor EPZ015666. We observed a dose-dependent efficacy of EPZ015666 in suppressing cell growth in MYC-driven MB cell lines. We also observed a superior efficacy of this inhibitor against MYC-driven MB cells compared to non-MYC MB cells. Together, our results implicate the regulation of MYC oncoprotein by PRMT5, and suggest that targeting PRMT5 could be a potential therapeutic strategy for MYC-driven MB and other MYC-driven cancers. Citation Format: Nagendra K. Chaturvedi, Varun Kesherwani, Matthew J. Kling, Sutapa Ray, Timothy R. McGuire, Shantaram S. Joshi, J. Graham Sharp, Don W. Coulter. The role of PRMT5 in MYC-driven medulloblastoma [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 1249.
Electroencephalography-Guided Anesthetic Administration and Postoperative Delirium—Reply
Authors: Troy S. Wildes, Angela M. Mickle, Michael S. Avidan
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Abstract 11584: Direct Oral Anti-coagulation Significantly Reduces Mortality in Atrial Fibrillation
Authors: Ronen Arbel, Ruslan Sergienko, Ariel Hammerman, Sari Greenberg-Dotan, Erez Batat, Orly Avnery, Dan Greenberg, Martin H Ellis
Journal: Circulation (2017)

Introduction: Direct anticoagulants (DOACs) have demonstrated significant reduction in stroke and all-cause mortality rates in non-valvular atrial fibrillation (NVAF) patients. However, utilization...
Post ESD bleeding prevention: Are polyglycolic acid sheets here to stay?
Authors: Seiichiro Abe
Journal: Endoscopy (2019)

Endoscopic submucosal dissection (ESD) has been widely accepted as a minimally invasive treatment of early gastric cancer without risk of lymph node metastasis [1]. ESD is technically demanding even for expert endoscopists, and several techniques and devices have been introduced as a result. A recent large, multicenter, prospective, cohort study from Japan demonstrated rates of 99.2 % for en bloc resection and 91.6 % for R0 resection. Intraoperative perforation was reported to be 2.3 % and was mostly managed by endoscopic clip closure, and emergency surgery was rarely performed [2]. Furthermore, several studies have demonstrated excellent long-term outcomes [1] [3].
Evaluation of prognostic factors after induction therapy in AML.
Authors: Craig E. Devoe, Delong Bao, Christina Trotta, Chung-Shien Lee, Joanna Stein Fishbein
Journal: Journal of Clinical Oncology (2019)

e18528 Background: Acute myeloid leukemia (AML) is a hematologic myeloid malignancy that carries a poor prognosis. Standard of care is induction chemotherapy with daunorubicin and cytarabine also known as 7 + 3. Bone marrow aspirates are assessed on day 14 (D14) and day 28 (D28). Achievement of CR (complete remission) is predicative of overall survival (OS ).Morphological review of BM (bone marrow) on D14 remains the standard evaluation for any indication for CR. Methods: Our primary objective was to determine if blast % on the D14 bone marrow aspirate is a prognostic indicator for remission in acute leukemia patients who underwent induction chemotherapy. Institutional review board was approved. A retrospective chart review was conducted at North Shore University Hospital. Adult patients with AML who received standard induction chemotherapy from 2010 to 2015 were included. 150 patients were reviewed and their D14 blast %, initial marrow blast %, gender, age, cytogenetics and initial WBC were assessed. The patients’ D14 blast % biopsies were divided into blast percentiles: &lt; 1%, 1-10%, 10-30%, 30-60% and &gt; 60%. CR was defined as patients having &lt; 5% blasts on their D28 bone marrow or day 63 and corresponding neutrophil count &gt; 1,000 and platelet count &gt; 100,000. Results: Fisher’s exact test was used to compare the proportion of patients who reached CR among the D14 blast % categories. The Wilcoxon test was utilized to compare CR on continuous variables. Results were considered statistically significant if p &lt; 0.05. D14 hemoglobin and D14 platelets were not significantly associated with CR status (p = 0.67, p = 0.33, and p = 0.13, respectively). D14 WBC was significantly associated with CR (p = 0.02), but when both D14 WBC and initial blasts % were included in a multiple logistic model, WBC was no longer a significant predictor of outcome. Only initial blast percent at time of diagnosis was deemed predictive of CR response at day D63 (p = 0.0142). Conclusions: Initial blast &gt; 60% was found to be significantly associated with the greatest CR rate. This study provides evidence of initial blast % being a prognostic factor for CR.
Abstract 12333: Optimizing the Follow-Up of Pediatric Patients With Pacemakers or Defibrillators Within the New England Community
Authors: Elsie Helou, Michael R Epstein, Cynthia Hutt, Shailendra Upadhyay, Bridget Boss, Niels Giddins, Kathleen M Rotondo, Anna Tsirka, David Kane, Lars Erickson, Elizabeth DeWitt, John K Triedman, Douglas Y Mah
Journal: Circulation (2018)

Introduction: The use of cardiac rhythm medical devices (CRMD) in the pediatric community is growing. Regular follow-up is recommended to ensure the adequate functioning and safety of these devices...
Totality of evidence in development of the bevacizumab biosimilar ABP 215: Central and investigator evaluation of efficacy from the MAPLE study.
Authors: Michael Thomas, Nick Thatcher, Jerome H Goldschmidt, Yuichiro Ohe, Helen McBride, Vladimir Hanes
Journal: Journal of Clinical Oncology (2019)

e20708 Background: ABP 215 (MVASI™ [bevacizumab]) is the first biosimilar to Avastin (bevacizumab) approved in the US and EU. This phase 3, double-blind study compared efficacy of ABP 215 with bevacizumab reference product (RP) in patients with advanced non-squamous NSCLC. Here we report the totality of evidence supporting similarity between ABP 215 and RP, including preclinical VEGF-A isoform binding relevant to the mechanism of action across indications, and clinical results of central and investigator evaluation of tumor response. Methods: VEGF-A kinetic parameters were compared for common isoforms 121, 165 and 189. Patients were randomized 1:1 to ABP 215 or RP 15 mg/kg Q3Wx6 cycles. All patients received carboplatin and paclitaxel Q3W for up to 6 cycles. Disease assessments (CT/MRI) were performed at screening, weeks 7, 13, 19, and Q9W thereafter by the investigator and, independently, by central, blinded radiologists. Efficacy was based on objective tumor assessments according to RECIST 1.1. Copies of all radiographs were submitted for central analysis. The primary efficacy endpoint was risk ratio of objective response rate (ORR); clinical equivalence was confirmed if the 2-sided 90% CI of the risk ratio was within the margin of 0.67-1.5. Additional efficacy analyses included duration of response (DOR) and progression-free survival (PFS). Results: Binding to all 3 isoforms was similar for ABP 215 and RP. In the MAPLE study, 642 patients (ABP 215, 328; RP, 314) were randomized. Based on central analysis, ORR was achieved in 128 (39.0%) patients in the ABP 215 and 131 (41.7%) in the RP groups, (ORR risk ratio: 0.93 [90% CI: 0.80, 1.09]). Based on investigator analysis, ORR was achieved in 157 (47.9%) patients in the ABP 215 and 151 (48.1%) in the RP groups (ORR risk ratio: 1.01 [90% CI: 0.88, 1.16]). Hazard ratio (HR, ABP 215 vs RP) for DOR was 1.08 (95% CI, 0.76, 1.54) and 0.76 (95% CI, 0.48, 1.23) per investigator and central assessment. PFS HR was 1.10 (90% CI, 0.92, 1.33) and 1.03 (90% CI, 0.83, 1.29) per investigator and central assessment. Conclusions: These results further confirm the similarity of ABP 215 and RP and support extrapolation to all available bevacizumab indications. Clinical trial information: NCT01966003.
Second cancer incidence in CLL patients receiving BTK inhibitors.
Authors: David Alan Bond, Ying Huang, James L Fisher, Amy S. Ruppert, Dwight Hall Owen, Erin Marie Bertino, Kerry Anne Rogers, Seema Ali Bhat, Samantha Mary Jaglowski, Michael R. Grever, John C. Byrd, Kami J. Maddocks, Jennifer Ann Woyach
Journal: Journal of Clinical Oncology (2019)

7511 Background: Patients (pts) with chronic lymphocytic leukemia (CLL) suffer morbidity and mortality from CLL and increased risk for second primary neoplasia (SPN). BTK inhibitors (BTKi) are highly effective for the treatment (tx) of CLL and are associated with partial restoration of immune function with ongoing tx. The impact of BTKi on the risk for and patterns of SPN is yet to be characterized. Methods: CLL pts treated with ibrutinib or acalabrutinib at our center were identified retrospectively. Baseline (bl) and outcome data were collected including incidence (inc) of Richter’s transformation (RT), non-melanoma skin cancer (NMSC), and SPN. Standard inc ratio (SIR) with 95% confidence intervals (CI) were calculated using expected inc rates from the Surveillance, Epidemiology, and End Results Program, assuming a Poisson distribution for the observed inc. Cumulative inc (CIR) of SPN (excluding RT and NMSC) was calculated from BTKi start date to the diagnosis of SPN; death was a competing risk and pts without event were censored at last follow-up (f/u). SPN was correlated with bl data using the Fine-Gray model. Results: 691 pts were included; median age was 64 years (y), median prior lines of treatment (tx) was 2 (20% tx-naïve, 66% with prior chemo-immunotherapy), and 56% were never smokers. At median f/u of 44 months, 68 pts (10%) were diagnosed (dx) with SPN (SIR 2.4, CI 1.9-3.0) including 13 lung (SIR 3.2, CI 1.7-5.5), 9 melanoma (SIR 6.9, CI 3.1-13), 9 prostate (SIR 1.4, CI 0.6-2.6), 7 bladder (SIR 5.2, CI 2.1-10.6) cancers. CIR of SPN at 3 y was 7.6% (Table). Smoking (hazard ratio (HR) 2.9, CI 1.7-5.0, p &lt; .01) and low bl CD8 count (HR 0.9 for 2-fold increase, CI 0.8-0.9, p &lt; .01) were associated with higher inc of SPN. RT was dx in 58 pts (8%) and NMSC in 138 pts (20%). 179 pts had died with 3 y overall survival of 79% (CI 76-82); the most common causes of death were CLL/RT (57%) and SPN (13%). Conclusions: The inc of SPN in pts treated with BTKi for CLL is increased relative to the general population. With a 5 y CIR of NMSC and SPN of 23% and 12%, these data support consideration of intensive cancer screening for CLL pts receiving BTKi. [Table: see text]
Abstract 3389: Analysis of the hepatocellular carcinoma transcriptome reveals dysregulation in pathways implicated in immunotherapy efficacy
Authors: Wei Tse Li, Christine O. Honda, Yuanhao Qu, Thomas K. Honda, Omar A. Saad, Jessica Wang-Rodriguez, Weg M. Ongkeko
Journal: Cancer Research (2019)

Abstract Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality in the world, but current treatment options are very limited in efficacy for patients who are diagnosed late, which often occurs because of limitations in current screening methods. Immunotherapy has emerged in recent years as arguably the most effective treatment for advanced HCC, but the failure of a large percentage of patients to respond to immunotherapy remains the ultimate obstacle to successful treatment. A phase I clinical trial with CTLA-4 checkpoint blockade has only achieved a 17.6% partial response rate in patients with advanced HCC, while another clinical trial using the PD-1 checkpoint inhibitor nivolumab has reported 18% partial response. Etiology-associated dysregulation of immune-associated (IA) genes may be able to explain the development of this differential clinical response. Using large-scale RNA-sequencing data from The Cancer Genome Atlas (TCGA), we identified immune-associated genes potentially dysregulated by alcohol or viral hepatitis B in HCC. Thirty-four dysregulated IA genes exhibiting significant correlation of gene expression to survival data and clinical variables were identified. To investigate the molecular mechanism for their dysregulation and explore the possibility of genome-based patient stratification, we profiled the correlation of all genomic alterations in HCC patients to IA gene expression using the information theory-based algorithm REVEALER. We also studied gene expression regulators and identified multiple microRNAs implicated in HCC pathogenesis that can potentially regulate these IA genes’ expression. Finally, we validated the dysregulation of several genes by alcohol, including the downregulation of NDRG2 and SOCS2, in vitro using HCC cell lines. Our study identified several potentially key pathways, including the IL-7 pathway, TNFRSF4 (OX40)- NF-κB pathway, and IL-10 pathway, that may be targeted in HCC immunotherapy treatments as well as possible sources of dysregulation for pathways known to be implicated in HCC immunotherapy efficacy. Lastly, we present microRNAs as promising therapeutic targets for dysregulated IA genes because of their extensive regulatory roles in the cancer immune landscape. Citation Format: Wei Tse Li, Christine O. Honda, Yuanhao Qu, Thomas K. Honda, Omar A. Saad, Jessica Wang-Rodriguez, Weg M. Ongkeko. Analysis of the hepatocellular carcinoma transcriptome reveals dysregulation in pathways implicated in immunotherapy efficacy [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 3389.