tbuckley/cabot-search huggingface dataset:
Effect of a 4-Food Elimination Diet and Omeprazole in Children with Eosinophilic Esophagitis – A Randomized, Controlled Trial
Authors: Ralf G. Heine, Rachel Peters, Don J. Cameron, George Alex, Mark R. Oliver, Winita Hardikar, Chung W. Chow, Vicki L. McWilliam, David J. Moore, Alyson M. Kakakios, Eric Cheah, Edward V. O'Loughlin, Christine Axelrad, Katrina Allen
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 12025: Higher Lactate Oxygen Index Rather than Artery Lactate Indicate Poor 24h-survival After Resuscitation in a Porcine Model of Prolonged Cardiac Arrest
Authors: Xiaozhu Zhai, Zhengfei Yang, Longyuan Jiang, Cai Wen, Houzhen Zheng, Tao Yu, Mary A Peberdy, Joseph P Ornato, Wanchun Tang
Journal: Circulation (2016)

Introduction: Increases in arterial lactate concentration (ALac) and cerebral lactate oxygen index (LOI) are documented indicators of poor prognosis in critically ill patients. In the present study, we investigated the changes of ALac and LOI after successful cardiopulmonary resuscitation (CPR) in a porcine model of prolonged cardiac arrest (CA). Hypothesis: Lactate oxygen index serves as a more sensitive indicator of post resuscitation survival than arterial lactate. Methods: Twelve male domestic pigs weighing 40 ± 3kg were studied. Ventricular fibrillation was electrically induced and untreated for 10 min. All animals were successfully resuscitated. Blood gas samples were obtained from the internal jugular vein and abdominal descending aorta at baseline (BL), 30 min and 120 min after resuscitation (PR). LOI was calculated based on the arterial (CaO 2 ) and jugular venous oxygen (CjO 2 ) content: CaO 2 = (1.34 х Hb х SaO 2 ) + (0.003 х paO 2 ), CjO 2 = (1.34 х Hb х SjO 2 ) + (0.003 х pjO 2 ), LOI = -(arterial lactate-jugular vein lactate)/(CaO 2 -CjO 2 ). Results: Five animals died in &lt;24 h after initial resuscitation and the other seven survived &gt; 24 h. The level of ALac in all animals increased significantly at PR30 and returned to BL at PR120. No significant differences in ALac were observed between survivors and non-survivors. LOI was increased in all animals after resuscitation when compared with BL. We observed significantly higher LOI levels at PR30 and PR120 in non-survivors vs. survivors. Conclusions: Higher LOI levels after resuscitation indicate poor 24 h survival in a pig model of prolonged CA.
MGTA-145 in Combination with Plerixafor Rapidly Mobilizes High Numbers of Hematopoietic Stem Cells and Graft-Versus-Host Disease Inhibiting Myeloid-Derived Suppressor Cells in Non-Human Primates
Authors: Kevin A. Goncalves, Patrick C. Falahee, Sharon L. Hyzy, Shuping Li, Anthony E. Boitano, Dwight M. Morrow, Michael P. Cooke
Journal: Blood (2018)
Abstract 17181: Impact of Interaction Between Vascular Access Site and Systolic Blood Pressure on Mortality in Patients Treated With Primary Percutaneous Coronary Intervention
Authors: Istvan Hizoh, Gyongyver Banhegyi, Zalan Gulyas, Dominika Domokos, Zsuzsanna Majoros, Laszlo Major, Robert Gabor Kiss
Journal: Circulation (2017)

Introduction: The mortality benefit of transradial primary PCI has been shown by several trials. However, it is less known whether this holds true for patients with hemodynamic instability. We studied the effect of a possible interaction between access site and systolic blood pressure (SBP) at admission on all-cause mortality at one year in patients treated with primary PCI. Methods: We analyzed data of 1255 consecutive cases from a prospective unicenter registry using multivariable Cox modeling. One-year mortality was 14.7% (185 patients). Restricted cubic splines were used to explore presence of non-linear relationships of the continuous predictors to log relative hazards. To avoid overfitting and determine the most relevant ones from the 24 candidate predictors including the non-linear interaction between access site and SBP, backward variable selection was combined with bootstrap resampling. Variables selected in at least 60% of the 10000 samples were included in the final model, which has been valida...
Abstract 18201: Acetylation of Mitochondrial Proteins Alters Fatty Acid β-Oxidation in Skeletal Muscle and Limits Exercise Capacity in Post-Infarct Heart Failure in Mice
Authors: Masaya Tsuda, Arata Fukushima, Junichi Matsumoto, Shingo Takada, Takashi Yokota, Takaaki Furihata, Takashi Katayama, Takayuki Nakajima, Hideo Nambu, Satoshi Maekawa, Ryosuke Shirakawa, Naoya Kakutani, Yoshikuni Obata, Katsuma Yamanashi, Koichi Okita, Shintaro Kinugawa
Journal: Circulation (2017)

Background: Skeletal muscle abnormalities including impaired energy metabolism in mitochondria have been shown to play a prominent role in lowered exercise capacity in heart failure (HF). Mitochond...
Treatment of Desmoid Tumors in 2019
Authors: Alessandro Gronchi, Robin L. Jones
Journal: JAMA Oncology (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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Oncology journal
Addition of Crenolanib to Induction Chemotherapy Overcomes the Poor Prognostic Impact of Co- Occurring Driver Mutations in Patients with Newly Diagnosed FLT3-Mutated AML
Authors: Aaron D Goldberg, Robert H. Collins, Richard M. Stone, Roland B. Walter, Chatchada Karanes, Carlos E Vigil, Eunice S. Wang, Martin S. Tallman
Journal: Blood (2018)
Prognostic and Immune-Related Factors for Response to Duvelisib in the Phase 2 DYNAMOTM Clinical Trial in iNHL
Authors: Pier Luigi Zinzani, Ian W. Flinn, Carole B. Miller, Scott A. Tetreault, Kirit M. Ardeshna, NgocDiep Le, Jonathan A. Pachter, Kam Sprott, Stephanie Lustgarten, David T. Weaver, Nina D. Wagner-Johnston
Journal: Blood (2018)
The activation of H3/H4 histamine receptors induces a decrease in cholangiocarcinoma growth
Authors: Heather Francis, Sharon DeMorrow, Julie Venter, Shelley Kopriva, Bradley Vaculin, Jennifer Savage, Gianfranco Alpini
Journal: Cancer Research (2008)

3602  Histamine regulates many functions including mitosis by binding to four histamine G-coupled receptors (HRH1, HRH2, HRH3 and HRH4). In rodents, while HRH1 and HRH2 modulate the activation of cholangiocyte growth, HRH3/H4 inhibit cholangiocyte hyperplasia. We have shown that the: (i) HRH3/H4 agonist, RAMH, inhibits in vitro the growth of the extra-hepatic cholangiocarcinoma cell line, Mz-ChA-1; and (ii) IP3/Ca2+/PKC/MAPK pathway regulates cholangiocarcinoma growth. The aims of the study were to evaluate: (i) the expression of the four histamine receptors in intra- and extra-hepatic cholangiocarcinoma cell lines; (ii) if RAMH stimulation suppresses the growth of these cholangiocarcinoma cell lines with different biliary origin; (iii) the signaling mechanisms regulating RAMH effects on Mz-ChA-1 growth; and (iv) the effects of RAMH on xenograft tumor growth in nude mice. Methods: Intra- (HuH-28, CCLP, HuCCT and SG231) and extra-hepatic (Mz-ChA-1 and TFK-1) cell lines were used along with non-malignant, immortalized cholangiocytes (H69). The expression of the four histamine receptors was evaluated by immunoblots and qPCR. Growth was measured in the different cell lines stimulated with RAMH (0-200 μM) by MTS assay. Proliferation was also evaluated in Mz-ChA-1 cells stimulated with HRH1 and HRH2 agonists. Intracellular IP3 and cAMP levels were evaluated by RIA in Mz-ChA-1 cells stimulated with 0.2% BSA (basal) or RAMH (10 μM). Phosphorylation of Ca2+-dependent PKC isoforms, and MAPKinases was evaluated by immunoblots in Mz-ChA-1 cells treated with 0.2% BSA or RAMH (10 μM). Knockdown of PKCα with siRNA was performed in Mz-ChA-1 cells in the absence or presence of RAMH (10 μM). Tumor growth studies were performed in BALB/c nude (nu/nu) mice implanted subcutaneously with Mz-ChA-1 cells and subsequently treated with daily IP injections of vehicle or RAMH (1000 mg/kg body weight in NaCl) for 44 days. Results: All cell lines studied expressed the four histamine receptors. Stimulation with RAMH inhibited the growth of all the cholangiocarcinoma cell lines (but not H69) at 48 hours, persisting up to 72 hours. HRH1 and HRH2 agonists increased Mz-ChA-1 cell growth. Intracellular IP3 (but not cAMP) levels were increased in Mz-ChA-1 cells stimulated with RAMH compared to basal. RAMH increased the phosphorylation of PKCα (but not PKCβI, βII and γ) and decreased the phosphorylation of ERK1/2 (but not p38 and JNK) of Mz-ChA-1 cells compared to their corresponding basal values. Following PKCα silencing, RAMH did not decrease the growth of Mz-ChA-1 cells. In a nude mouse model, RAMH inhibited Mz-ChA-1 cell growth in vivo. Conclusion: RAMH inhibits intra- and extra-hepatic cholangiocarcinoma growth via activation of the PLC/IP3/Ca2+/PKCα/ERK1/2 (but not cAMP/PKA) pathway. The interaction of histamine with HRH3/H4 may be important in the management of cholangiocarcinoma.
Long-Term Risk of Hospitalization Among Five-Year Survivors of Childhood Leukemia in the Nordic Countries
Authors: Gitte Vrelits Sørensen, Jeanette Falck Winther, Sofie de Fine Licht, Klaus Kaa Andersen, Anna Sällfors Holmqvist, Laura Madanat-Harjuoja, Laufey Tryggvadottir, Andrea Bautz, Timothy L Lash, Henrik Hasle
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Background Adverse effects from childhood leukemia treatment may persist or present years after cure from cancer. We provide a comprehensive evaluation of subsequent hospitalization in five-year survivors of childhood acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). Methods In the Adult Life after Childhood Cancer in Scandinavia Study, we identified 4003 five-year survivors diagnosed with childhood leukemia 1970–2008 in Denmark, Sweden, Iceland, and Finland. Survivors and 129 828 population comparisons were followed for first-time nonpsychiatric hospitalizations for 120 disease categories in the hospital registries. Standardized hospitalization rate ratios and absolute excess rates were calculated. All statistical tests were two-sided. Results Survivors of ALL (n = 3391), AML (n = 389), and CML (n = 92) had an increased overall hospitalization rate compared with population comparisons. The rate ratio for any hospitalization was 1.95 (95% confidence interval [CI] = 1.83 to 2.07) in ALL, 3.09 (95% CI = 2.53 to 3.65) in AML, and 4.51 (95% CI = 3.03 to 6.00) in CML survivors and remained increased even 20 years from leukemia diagnosis. Corresponding absolute excess rates per 1000 person-years were 28.48 (95% CI = 24.96 to 32.00), 62.75 (95% CI = 46.00 to 79.50), and 105.31 (95% CI = 60.90 to 149.72). Conclusion Leukemia survivors have an increased rate of hospitalization for medical conditions. We provide novel insight into the relative and absolute rate of hospitalization for 120 disease categories in survivors of ALL, AML, and CML, which are likely to be informative for both survivors and healthcare providers.
Association of Donor T Cell Repertoire in Host Lymphoid and Target Organs and Gvhd Development
Authors: Yongxia Wu, Jianing Fu, Anusara Daenthanasanmak, Hung D Nguyen, Mohammed Hanief Sofi, Jessica Lauren Heinrichs, Yuejun Liu, Steven Douglas Schutt, David Bastian, Xue-Zhong Yu
Journal: Blood (2018)
Nrf2-miR-129-3p-mTOR Axis Controls an miRNA Regulatory Network Involved in HDACi-Induced Autophagy
Authors: Weijian Sun, Yongdong Yi, Guojun Xia, Yaxin Zhao, Yaojun Yu, Liyi Li, Chunya Hua, Bin He, Beng Yang, Chengyang Yu, Chenmin Ye, Fuyang Tu, Canjin Chen, Xiaoying Xu, Zhiqiang Zheng, Wenqian Wang, Xian Shen
Journal: Molecular Therapy (2019)

Histone deacetylase inhibitors (HDACis) are the recommended treatment for many solid tumors; however, resistance is a major clinical obstacle for their efficacy. High levels of the transcription factor nuclear factor erythroid 2 like-2 (Nrf2) in cancer cells suggest a vital role in chemoresistance, and regulation of autophagy is one mechanism by which Nrf2 mediates chemoresistance. Although the molecular mechanisms underlying this activity are unclear, understanding them may ultimately improve therapeutic outcomes following HDACi treatment. In this study, we found that HDACi treatment increased Nrf2 mRNA and protein levels and enhanced Nrf2 transcriptional activity. Conversely, Nrf2 knockdown or inhibition blocked HDACi-induced autophagy. In addition, a microRNA (miRNA) array identified upregulation of miR-129-3p in response to Nrf2 overexpression. Chromatin immunoprecipitation assays confirmed miR-129-3p to be a direct Nrf2 target. RepTar and RNAhybrid databases indicated mammalian target of rapamycin (mTOR) as a potential miR-129-3p target, which we experimentally confirmed. Finally, Nrf2 inhibition or miR-129-3p in combination with HDACis increased cell death in vitro and in vivo. Collectively, these results demonstrated that Nrf2 regulates mTOR during HDACi-induced autophagy through miRNA-129-3p and inhibition of this pathway could enhance HDACi-mediated cell death.
Increased risk of pseudoprogression among pediatric low-grade glioma patients treated with proton versus photon radiotherapy
Authors: Ethan B Ludmir, Anita Mahajan, Arnold C Paulino, Jeremy Y Jones, Leena M Ketonen, Jack M Su, David R Grosshans, Mary Frances McAleer, Susan L McGovern, Yasmin A Lassen-Ramshad, Adekunle M Adesina, Robert C Dauser, Jeffrey S Weinberg, Murali M Chintagumpala
Journal: Neuro-Oncology (2019)

Pseudoprogression (PsP) is a recognized phenomenon after radiotherapy (RT) for high-grade glioma but is poorly characterized for low-grade glioma (LGG). We sought to characterize PsP for pediatric LGG patients treated with RT, with particular focus on the role of RT modality using photon-based intensity-modulated RT (IMRT) or proton beam therapy (PBT).Serial MRI scans from 83 pediatric LGG patients managed at 2 institutions between 1998 and 2017 were evaluated. PsP was scored when a progressive lesion subsequently decreased or stabilized for at least a year without therapy.Thirty-two patients (39%) were treated with IMRT, and 51 (61%) were treated with PBT. Median RT dose for the cohort was 50.4 Gy(RBE) (range, 45-59.4 Gy[RBE]). PsP was identified in 31 patients (37%), including 8/32 IMRT patients (25%) and 23/51 PBT patients (45%). PBT patients were significantly more likely to have post-RT enlargement (hazard ratio [HR] 2.15, 95% CI: 1.06-4.38, P = 0.048). RT dose >50.4 Gy(RBE) similarly predicted higher rates of PsP (HR 2.61, 95% CI: 1.20-5.68, P = 0.016). Multivariable analysis confirmed the independent effects of RT modality (P = 0.03) and RT dose (P = 0.01) on PsP incidence. Local progression occurred in 10 patients: 7 IMRT patients (22%) and 3 PBT patients (6%), with a trend toward improved local control for PBT patients (HR 0.34, 95% CI: 0.10-1.18, P = 0.099).These data highlight substantial rates of PsP among pediatric LGG patients, particularly those treated with PBT. PsP should be considered when assessing response to RT in LGG patients within the first year after RT.
Cystathionine as a marker for 1p/19q codeleted gliomas by in vivo magnetic resonance spectroscopy
Authors: Francesca Branzoli, Clément Pontoizeau, Lucien Tchara, Anna Luisa Di Stefano, Aurélie Kamoun, Dinesh K Deelchand, Romain Valabrègue, Stéphane Lehéricy, Marc Sanson, Chris Ottolenghi, Małgorzata Marjańska
Journal: Neuro-Oncology (2019)

Codeletion of chromosome arms 1p and 19q (1p/19q codeletion) highly benefits diagnosis and prognosis in gliomas. In this study, we investigated the effect of 1p/19q codeletion on cancer cell metabolism and evaluated possible metabolic targets for tailored therapies. We combined in vivo 1H (proton) magnetic resonance spectroscopy (MRS) measurements in human gliomas with the analysis of a series of standard amino acids by liquid chromatography–mass spectroscopy (LC-MS) in human glioma biopsies. Sixty-five subjects with low-grade glioma were included in the study: 31 underwent the MRI/MRS examination, 47 brain tumor tissue samples were analyzed with LC-MS, and 33 samples were analyzed for gene expression with quantitative PCR. Additionally, we performed metabolic tracer experiments in cell models with 1p deletion. We report the first in vivo detection of cystathionine by MRS in 1p/19q codeleted gliomas. Selective accumulation of cystathionine was observed in codeleted gliomas in vivo, in brain tissue samples, as well as in cells harboring heterozygous deletions for serine- and cystathionine-pathway genes located on 1p: phosphoglycerate dehydrogenase (PHGDH) and cystathionine gamma-lyase (CTH). Quantitative PCR analyses showed 40–50% lower expression of both PHGDH and CTH in 1p/19q codeleted gliomas compared with their non-codeleted counterparts. Our results provide strong evidence of a selective vulnerability of codeleted gliomas to serine and glutathione depletion and point to cystathionine as a possible noninvasive marker of treatment response.
Anatomical topography of the tumor is related to prognostic survival in adenocarcinoma of esophagogastric junction?: Multivariable analysis.
Authors: Flavio Roberto Takeda, Rubens Antonio Aissar Sallum, Ulysses Ribeiro, Tiago Bianchi de Castria, Francisco Tustumi, Julio Rafael Mariano Rocha, Ivan Cecconello
Journal: Journal of Clinical Oncology (2019)

108 Background: The adenocarcinoma of the esophagogastric junction (AJEG) is divided according to its anatomopathological classification (Siewert classification) for the choice of surgical treatment. However, both the Siewert classification and the location of the AJEG are related to different prognoses reported in the literature. Objectives: To compare the survival of patients with AJEG submitted to surgical treatment according to different topographies in the esophagogastric junction. Methods: 147 patients were selected between 2000 and 2016. One hundred and thirty (88%) males, mean age 64 years. Analyzing the retrieved lymph nodes, affected and the relation of resected and affected. AEGG (E: esophagus, E/TEG: gastric esophagus, TEG: gastric esophagus transition, TEG/G: esophageal gastric and stomach transition, and E/TEG/G: esophagus, transition and stomach) were analyzed for global survival, free of disease, and after relapse. Results: In relation to epidemiological data, the mean age was 63.1 years. Of the 147 patients 90 (61.2%) were submitted to neoadjuvant treatment. There was no statistical difference between the groups regarding histological grade, pT, pN, stage, tumor extension, lymphatic, venous and perineural invasion. The mean extension of the tumor was 5.4 cm. The mean number of retrieved lymphnodes were 32. Overall survival was E: 90%, E/TEG: 60%, TEG: 52%, TEG/G: 50% and E/TEG/G: 21%. (p &lt;0.0001). Disease free of survival was E: 78%, E/TEG: 48%, TEG: 43%, TEG/G: 38% and E/TEG/G: 15%. (p &lt;0.001). Conclusions: The survival of the AJEG varies according to the topography of the lesion, the tumors located closer to the stomach present worse survival than those located in the esophagus, except when the tumor is very extensive, from the esophagus to the stomach.
A Combined Epidemiologic and Mechanistic Study of Endotoxin and Food Allergen Sensitization
Authors: Angela Tsuang, Alexander V. Grishin, Galina T. Grishina, Jade T. Andrade, Anh N. Do, Joanne Sordillo, Ginger L. Chew, Supinda Bunyavanich
Journal: Journal of Allergy and Clinical Immunology (2019)
Liver Expression of a MiniATP7B Gene Results in Long‐Term Restoration of Copper Homeostasis in a Wilson Disease Model in Mice
Authors: Oihana Murillo, Daniel Moreno, Cristina Gazquez, Miren Barberia, Itziar Cenzano, Iñigo Navarro, Iker Uriarte, Victor Sebastian, Manuel Arruebo, Veronica Ferrer, Bernard Bénichou, Jean Philippe Combal, Jesus Prieto, Ruben Hernandez‐Alcoceba, Gloria Gonzalez Aseguinolaza
Journal: Hepatology (2019)

Gene therapy with an adeno‐associated vector (AAV) serotype 8 encoding the human ATPase copper‐transporting beta polypeptide (ATP7B) complementary DNA (cDNA; AAV8‐ATP7B) is able to provide long‐term copper metabolism correction in 6‐week‐old male Wilson disease (WD) mice. However, the size of the genome (5.2 kilobases [kb]) surpasses the optimal packaging capacity of the vector, which resulted in low‐yield production; in addition, further analyses in WD female mice and in animals with a more advanced disease revealed reduced therapeutic efficacy, as compared to younger males. To improve efficacy of the treatment, an optimized shorter AAV vector was generated, in which four out of six metal‐binding domains (MBDs) were deleted from the ATP7B coding sequence, giving rise to the miniATP7B protein (Δ57‐486‐ATP7B). In contrast to AAV8‐ATP7B, AAV8‐miniATP7B could be produced at high titers and was able to restore copper homeostasis in 6‐ and 12‐week‐old male and female WD mice. In addition, a recently developed synthetic AAV vector, AAVAnc80, carrying the miniATP7B gene was similarly effective at preventing liver damage, restoring copper homeostasis, and improving survival 1 year after treatment. Transduction of approximately 20% of hepatocytes was sufficient to normalize copper homeostasis, suggesting that corrected hepatocytes are acting as a sink to eliminate excess of copper. Importantly, administration of AAVAnc80‐miniATP7B was safe in healthy mice and did not result in copper deficiency. Conclusion : In summary, gene therapy using an optimized therapeutic cassette in different AAV systems provides long‐term correction of copper metabolism regardless of sex or stage of disease in a clinically relevant WD mouse model. These results pave the way for the implementation of gene therapy in WD patients.