tbuckley/cabot-search huggingface dataset:
Schlafen 4–expressing myeloid-derived suppressor cells are induced during murine gastric metaplasia
Authors: Lin Ding, Michael M. Hayes, Amanda Photenhauer, Kathryn A. Eaton, Qian Li, Ramon Ocadiz-Ruiz, Juanita L. Merchant
Journal: Journal of Clinical Investigation (2016)

Chronic Helicobacter pylori infection triggers neoplastic transformation of the gastric mucosa in a small subset of patients, but the risk factors that induce progression to gastric metaplasia have not been identified. Prior to cancer development, the oxyntic gastric glands atrophy and are replaced by metaplastic cells in response to chronic gastritis. Previously, we identified schlafen 4 (Slfn4) as a GLI1 target gene and myeloid differentiation factor that correlates with spasmolytic polypeptide-expressing metaplasia (SPEM) in mice. Here, we tested the hypothesis that migration of SLFN4-expressing cells from the bone marrow to peripheral organs predicts preneoplastic changes in the gastric microenvironment. Lineage tracing in Helicobacter-infected Slfn4 reporter mice revealed that SLFN4+ cells migrated to the stomach, where they exhibited myeloid-derived suppressor cell (MDSC) markers and acquired the ability to inhibit T cell proliferation. SLFN4+ MDSCs were not observed in infected GLI1-deficient mice. Overexpression of sonic hedgehog ligand (SHH) in infected WT mice accelerated the appearance of SLFN4+ MDSCs in the gastric corpus. Similarly, in the stomachs of H. pylori-infected patients, the human SLFN4 ortholog SLFN12L colocalized to cells that expressed MDSC surface markers CD15+CD33+HLA-DRlo. Together, these results indicate that SLFN4 marks a GLI1-dependent population of MDSCs that predict a shift in the gastric mucosa to a metaplastic phenotype.
Abstract 3229: Microglia/macrophages activation status in diffuse gliomas
Authors: Thais F. Galatro, Paula Sola, Sueli M. Oba-Shinjo, Bart J. Eggen, Suely K. Marie
Journal: Cancer Research (2016)

Abstract Diffuse gliomas are primary brain tumors characterized by infiltrative growth and high heterogeneity, which renders the disease mostly incurable. Advances in genetic analysis have characterized molecular and epigenetic alterations leading to impact on patients’ overall survival and clinical outcome, particularly in glioblastoma (GBM). However, glioma tumorigenicity is not controlled uniquely by its genetic alterations. The crosstalk between tumor cells and the surrounding microenvironment plays a crucial role in modulating glioma growth and aggressiveness. The most abundant non-neoplastic cells in this microenvironment belong to the myeloid lineage, comprising resident microglia, with central nervous system (CNS)-tailored functions, and infiltrating monocytes/macrophages from the bone marrow. Understanding the dynamics between tumor and myeloid cells and the correlation between oncogenic molecular alterations in the tumor and the inflammatory activation status of innate immunity cells would elucidate potential treatment alternatives. Our large cohort of human glioma consisted of both astrocytoma and oligodendroglioma tumors, ranging from grades II to IV. Using high-throughput DNA sequencing and immunohistochemistry, we have classified GBM samples in proneural, classical and mesenchymal. Next, we evaluated the activation status of microglia/macrophages within these samples. Despite the great heterogeneity, we observed higher levels of myeloid markers (IBA1, CD11b and CD68) in astrocytic tumors compared to oligodendrocytic ones and to non-neoplastic (NN) tissue. Anti-inflammation markers, such as CD163, are also more abundant in astrocytomas, as well as in the mesenchymal and classical GBM subtypes, while pro-inflammation markers, such as IL1-beta, show a more widespread expression throughout samples. Our preliminary data suggests an immune-suppressive and growth supportive characteristic for tumors with worse clinical outcome, linked to an activation profile of myeloid cells. Further exploring the characteristics and dynamics of innate immune cells within the microenvironment of different grades and subtypes of glioma is crucial for the better understanding of the disease progression. Citation Format: Thais F. Galatro, Paula Sola, Sueli M. Oba-Shinjo, Bart J. Eggen, Suely K. Marie. Microglia/macrophages activation status in diffuse gliomas. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3229.
Abstract LB-286: Dynamic alternative splicing correlates with drug synergy and induces novel gene regulatory networks in MCF7
Authors: Xintong Chen, Ali Bashir, Gustavo Stolovitzky, Bojan Losic
Journal: Cancer Research (2016)

Abstract Drug combination therapies in the cancer setting often succeed where mono-therapies fail, facilitating durable and robust responses that may curtail metastases and even be accompanied by milder side-effects. Here we incorporate transcriptional splicing dynamics with a gene level expression analysis to assess the transcriptional landscape of MCF-7 (ER+) cell-lines across mono or combination therapies in a time course short-read RNA-seq experiment. We leverage the most comprehensive known splicing database of MCF7 to assess the sensitivity and specificity our short-read splicing inference by interrogating the long-read PacBio isoform sequencing (IsoSeq) MCF7 database. We infer robust isoforms which are strongly associated with phenotypic synergy and demonstrate their novel functional role by computing gene-gene coexpression networks which are sensitive to their expression. Briefly, we use RNA-seq to study the transcriptional response over time (0, 3, 6, 9, 12, and 24 h) for three drugs (A, B and C) and their combinations (AB, AC and BC) in MCF-7 (ER+) breast cancer cells lines. Cell viability measurements show that one of the combinations (AB) is strongly synergistic, whereas the other two (AC and BC) are merely additive. We show that in addition to a novel transcriptional signature driven by differential expression, the combination AB transcriptional landscape is characterized by persistent alternative splicing signatures mostly comprised of genes which are not differentially expressed with respect to A or B, but whose functional role has been dramatically changed by the addition (deletion) of a key regulatory protein domain encoded by the extra(missing) exon. We integrate this synergistic splicing signal into a gene regulatory network (GRN) via adaptive network refinement to show that it strongly contributes to the emergence of extensive transcriptional cascades by creating and removing key gene-gene correlations and altering the modular structure of the network. Using this approach we show that a key (heretofor poorly understood) isoform of Protein beta-arrestin-1 (ARBB1), which participates in the desensitization of G-protein coupled receptors through intracellular response to Estrogen, becomes enriched in the calcium ion-dependent exocytosis coexpression module for synergistic therapies only, despite being absent in the baseline MCF-7 long-read PacBio IsoSeq data. Our results directly show that alternative splicing is crucial in any molecular characterization of phenotypic drug synergy in drug-tumor interactions. Citation Format: Xintong Chen, Ali Bashir, Gustavo Stolovitzky, Bojan Losic. Dynamic alternative splicing correlates with drug synergy and induces novel gene regulatory networks in MCF7. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-286.
Efficacy and safety of combined sequential treatment with radiofrequency ablation and sorafenib in patients with hepatocellular carcinoma in intermediate stage ineligible for tace: a prospective randomized open study
Authors: G. de Stefano, U. Scognamiglio, V. Iodice, N. Farella, E. Simeone, V. Montesarchio
Journal: Annals of Oncology (2015)
Predicting Therapy-Related Acute Myeloid Leukemia By Routine Laboratory Values: An Analysis Of 126 Patients With Breast Cancer Referred For Bone Marrow Biopsy At Memorial Sloan-Kettering Cancer Center
Authors: Eytan M Stein, Meier Hsu, Adam Goldrich, Ashwin Kishtagari, Sean M. Devlin, Martin S. Tallman, Gerald A. Soff, Rekha Parameswaran
Journal: Blood (2013)
Abstract 1395: Development and validation of NGS-based clinical cancer panels for precision medicine in Asian and Caucasian adult cancers
Authors: Winston Patrick Kuo, Amy Wang, Tak Cheng, Pan Du, Shidong Jia
Journal: Cancer Research (2016)

Abstract In the new era of precision medicine, comprehensive cancer panels are needed to identify actionable cancer genes and match patients to personalized therapies. Here, we report a Pan-Cancer NGS Panel designed by leaders in the field that comprises of all exon coding and selected hotspots of critical cancer genes in the most common cancer types for both Asian and Caucasian cohorts, including but not limited to lung, colon, breast and prostate cancer. The panel allows detection of known and novel variants in indication-specific signaling pathways, disease biology, DNA repair, and in particular drug resistance, to advance research into personalized cancer treatment and for use in clinical trials to help the development of new targeted therapies. Technical validation was performed to characterize point mutations, indels, copy number variations and fusions across clinically relevant, actionable cancer genes in both liquid biopsies and formalin-fixed paraffin-embedded (FFPE) clinical specimens. Assay sensitivity, specificity and accuracy were tested using reference samples with known genetic profiling and further validated on a variety of orthogonal platforms such as digital PCR, allele-specific PCR and Sanger sequencing. To the best of our knowledge, this is the first ethnic-specific NGS diagnostic test designed specifically for Asian and Caucasian adult cancer patients. Citation Format: Winston Patrick Kuo, Amy Wang, Tak Cheng, Pan Du, Shidong Jia. Development and validation of NGS-based clinical cancer panels for precision medicine in Asian and Caucasian adult cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1395.
Hematopoietic stem cell transplantation in immunocompetent hosts without radiation or chemotherapy
Authors: Akanksha Chhabra, Aaron M. Ring, Kipp Weiskopf, Peter John Schnorr, Sydney Gordon, Alan C. Le, Hye-Sook Kwon, Nan Guo Ring, Jens Volkmer, Po Yi Ho, Serena Tseng, Irving L. Weissman, Judith A. Shizuru
Journal: Science Translational Medicine (2016)

Hematopoietic stem cell (HSC) transplantation can cure diverse diseases of the blood system, including hematologic malignancies, anemias, and autoimmune disorders. However, patients must undergo toxic conditioning regimens that use chemotherapy and/or radiation to eliminate host HSCs and enable donor HSC engraftment. Previous studies have shown that anti-c-Kit monoclonal antibodies deplete HSCs from bone marrow niches, allowing donor HSC engraftment in immunodeficient mice. We show that host HSC clearance is dependent on Fc-mediated antibody effector functions, and enhancing effector activity through blockade of CD47, a myeloid-specific immune checkpoint, extends anti-c-Kit conditioning to fully immunocompetent mice. The combined treatment leads to elimination of >99% of host HSCs and robust multilineage blood reconstitution after HSC transplantation. This targeted conditioning regimen that uses only biologic agents has the potential to transform the practice of HSC transplantation and enable its use in a wider spectrum of patients.
Psycho-Therapeutics, or Treatment by Hypnotism and Suggestion.
Journal: JAMA (1892)

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
The Genomic Landscape of Pancreatic and Periampullary Adenocarcinoma
Authors: Vandana Sandhu, David C. Wedge, Inger Marie Bowitz Lothe, Knut Jørgen Labori, Stefan C. Dentro, Trond Buanes, Martina L. Skrede, Astrid M. Dalsgaard, Else Munthe, Ola Myklebost, Ole Christian Lingjærde, Anne-Lise Børresen-Dale, Tone Ikdahl, Peter Van Loo, Silje Nord, Elin H. Kure
Journal: Cancer Research (2016)

Abstract Despite advances in diagnostics, less than 5% of patients with periampullary tumors experience an overall survival of five years or more. Periampullary tumors are neoplasms that arise in the vicinity of the ampulla of Vater, an enlargement of liver and pancreas ducts where they join and enter the small intestine. In this study, we analyzed copy number aberrations using Affymetrix SNP 6.0 arrays in 60 periampullary adenocarcinomas from Oslo University Hospital to identify genome-wide copy number aberrations, putative driver genes, deregulated pathways, and potential prognostic markers. Results were validated in a separate cohort derived from The Cancer Genome Atlas Consortium (n = 127). In contrast to many other solid tumors, periampullary adenocarcinomas exhibited more frequent genomic deletions than gains. Genes in the frequently codeleted region 17p13 and 18q21/22 were associated with cell cycle, apoptosis, and p53 and Wnt signaling. By integrating genomics and transcriptomics data from the same patients, we identified CCNE1 and ERBB2 as candidate driver genes. Morphologic subtypes of periampullary adenocarcinomas (i.e., pancreatobiliary or intestinal) harbor many common genomic aberrations. However, gain of 13q and 3q, and deletions of 5q were found specific to the intestinal subtype. Our study also implicated the use of the PAM50 classifier in identifying a subgroup of patients with a high proliferation rate, which had impaired survival. Furthermore, gain of 18p11 (18p11.21-23, 18p11.31-32) and 19q13 (19q13.2, 19q13.31-32) and subsequent overexpression of the genes in these loci were associated with impaired survival. Our work identifies potential prognostic markers for periampullary tumors, the genetic characterization of which has lagged. Cancer Res; 76(17); 5092–102. ©2016 AACR.
Abstract 211: Apoptosis and Subclinical Atherosclerosis: Caspase-3 is Associated with Aortic Compliance and Coronary and Aortic Atherosclerosis in the Dallas Heart Study
Authors: Susan Matulevicius, Anand Rohatgi, Amit Khera, Sandeep R Das, Andrew Owens, Colby R Ayers, Carlos H Timaran, Eric B Rosero, Mark H Drazner, Ronald M Peshock, James A de Lemos
Journal: Circulation (2008)
Abstract 2677: Unfolded protein response is required for EMT-driven metastasis by inducing CREB3L1
Authors: Yuxiong Feng, Dexter X. Jin, Piyush B. Gupta
Journal: Cancer Research (2016)

Abstract Cancer initiates and progresses in the presence of a diversity of stresses ranging from nutrient deficiency, low oxygen supply to pH fluctuations. A set of stress response pathways, termed unfolded protein response (UPR), was evolved to maintain homeostasis of the endoplasmic reticulum (ER) from disruption by the above stressors. While it is broadly acknowledged that the UPR is involved in tumorigenesis, as tumor cells can employ the UPR as a critical survival strategy to grow and resist chemotherapy, the role of UPR in metastasis remains largely elusive. Epithelial-to-mesenchymal transition (EMT) is a cell transdifferentiation program frequently hijacked by cancer cells to migrate and invade. Here we showed cancer cells that have undergone an EMT employ the PERK-ATF4 branch of the UPR to drive metastasis, since loss of ATF4 abrogates the cell invasion upon an EMT. By conducting gene expression profiling, we found that the PERK-ATF4 pathway mediates the expression of a subset of the essential pro-invasion EMT-signature genes. In particular, CREB3L1, an ER-associated transcription factor (TF), is highly induced upon EMT in an ATF4-dependent manner. Knockdown of CREB3L1 effectively inhibits the EMT-driven invasion, while overexpression of CREB3L1 not only promotes invasion but also rescues the decrease of invasion caused by loss of ATF4. Mechanistically, CREB3L1 facilitates invasion through an ECM-FAK cascade. In breast cancer patients, the expression of CREB3L1 is significantly upregulated in breast cancer metastases compared to primary lesions, and predicts a poor prognosis. Most importantly, unlike other EMT-TFs, CREB3L1 could be inhibited by known chemicals, since the activation of CREB3L1 is mediated by the S1P- and S2P- dependent proteolysis. In an orthotopic breast cancer model, we found that chemical inhibition of CREB3L1 drastically suppresses lung metastasis. As a summary, we discovered that an ER stress-associated transcription factor CREB3L1 is required for cancer metastasis, and the susceptibility of CREB3L1 to chemical inhibition makes it a valuable target for drug development. Citation Format: Yuxiong Feng, Dexter X. Jin, Piyush B. Gupta. Unfolded protein response is required for EMT-driven metastasis by inducing CREB3L1. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2677.
2010 Clinical Trial/Clinical Science Abstracts
Journal: Circulation (2010)

Hall B 

Abstracts 21768–21828 

21768 

The Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT) 

Anthony S Tang, George A Wells, Univ of Ottawa Heart Institute, Ottawa, Canada; Mario Talajic, Institut de Cardiologie de Montreal, Montreal, Canada; J. Malcolm O Arnold, Univ Hosp, London Health Sciences Cntr, London, Canada; Robert Sheldon, Libin Cardiovascular Institute of Alberta, Calgary, Canada; Stuart Connolly, Hamilton Health Science Cntr, Hamilton, Canada; Stefan H Hohnloser, J.W. Goethe Universitat, Frankfurt, Germany; Graham Nichol, Univ of Washington-Harborview Med Cntr, Seattle, WA; David H Birnie, Univ of Ottawa Heart Institute, Ottawa, Canada; John L Sapp, Queen Elizabeth II Health Sciences Cntr, Halifax, Canada; Raymond Yee, London Health Sciences Cntr, London, Canada; Jeffrey S Healey, McMaster Univeristy, Hamilton, Canada; Jean L Rouleau; Universite de Montreal, Montreal, Canada

The role of cardiac resynchronization therapy (CRT) in patients with mild to moderate heart failure (HF) symptoms requiring an implantable cardioverter-defibrillator therapy (ICD) remains uncertain. We hypothesized that the addition of CRT to optimal medical therapy and ICD reduces mortality and HF hospitalization in patients with mild to moderate HF symptoms, LV dysfunction (EF less than or equal to 30%) and wide QRS duration. Design: This study is a prospective multicenter (34 sites in Canada, Europe, Australia, and Turkey) randomized double-blinded controlled clinical trial. Patients were randomized to receive an ICD (control) or ICD with CRT in a 1:1 ratio in addition to optimal heart failure medical therapy. The primary endpoint is a composite of all cause mortality and adjudicated HF hospitalization (defined as an admission to hospital for >24 hrs with a diagnosis of worsening HF) whichever comes first. Secondary endpoints include all cause mortality at anytime during the study, HF hospitalization, quality of life and cost effectiveness of therapy. Sample size: A total of 1798 patients satisfying the inclusion/exclusion criteria were enrolled between …
Lung cancer (LC) survival in relation to histologic subtype: Implications for LC prevention and early detection
Authors: G. M. Strauss, A. Jemal, M. B. McKenna, J. A. Strauss, K. M. Cummings
Journal: Journal of Clinical Oncology (2008)

1530 Background: We previously demonstrated in 307,797 LC pts entered on the SEER (Surveillance Epidemiology and End Results) database from 1975–2003 that adenocarcinoma (AD) is now the most common form of LC in the US (JTO, 2:S305, 2007). AD is most common in women and men, blacks and whites, and in all age groups. The epidemic of smoking-related AD relates to the introduction of low tar/light cigarettes by the Tobacco Industry (TI), which led smokers to compensate for low yields by inhaling more deeply and smoking more intensely. Objectives of this analysis is to examine 5-yr survival (5YrS) in relation to LC histology, and to explore whether improvements in 5YrS in recent decades (5% in 1950–1954, 8% in 1965–1969, 16% in 1995–2002) may reflect changes in histology. Methods: SEER data on 171,261 LC pts diagnosed from1980–2002 were analyzed to determine 5YrS of AD, squamous cell (SQ), small cell (SmC), and large-cell (LgC). Comparisons were drawn based upon stage (local disease [LD], regional [RD], and distant [DD]), gender, race, age, and yr of diagnosis. Results: 5YrS for all stages and histologies was15.3%, with only modest improvements over time. While disease stage was the most powerful predictor of 5YrS, histology was also a major predictor. For all stages, 5YrS was 20% in AD, 15% in SQ, 12% in LgC, and 6% in SmC. Nonetheless, stage distribution was most favorable in SQ. Improved 5YrS for AD relates to superior outcome in LD: AD-58%, SQ- 41%, LgC-40%, SmC-13%. In RD, 5YrS was only slightly better for AD; in DD, 5YrS was most favorable for SQ. When adjusted for stage and histology, 5YrS was better in females than males, whites than blacks, and was inversely related to age. Conclusions: 5YrS for lung AD is significantly superior to other histologies. Improved survival in AD primarily reflects differences in biologic behavior of localized AD, rather than improved stage distribution. The 5YrS difference for localized AD is particularly striking in women. The rise of AD appears to have contributed to modest improvement in 5YrS in recent decades. Dramatically improved 5YrS for localized AD underscores the importance of early detection for lung AD. More importantly, this project underscores the urgent need for comprehensive TI regulation to reduce the epidemic of smoking-related lung AD. No significant financial relationships to disclose.
Terlipressin Improves Renal Function and Reverses Hepatorenal Syndrome in Patients With Systemic Inflammatory Response Syndrome
Authors: Florence Wong, Stephen Chris Pappas, Thomas D. Boyer, Arun J. Sanyal, Jasmohan S. Bajaj, Shannon Escalante, Khurram Jamil
Journal: Clinical Gastroenterology and Hepatology (2016)