tbuckley/cabot-search huggingface dataset:
Abstract 5004: Profiling the extracellular matrix landscape of tumor microenvironments using proteomics
Authors: Alexandra Naba, Karl R. Clauser, Steven A. Carr, Richard O. Hynes
Journal: Cancer Research (2018)

Abstract "Your cancer has spread" remains for most cancer patients synonymous with a death sentence. Indeed, the majority of cancer deaths are due to metastases: the dissemination of tumor cells from a primary tumor to distant vital organs. As of today, we do not have efficient treatments to stabilize or cure most metastatic cancers, and for patients diagnosed early, i.e., before metastases are detectable, we do not have reliable markers to predict whether their tumors will remain indolent or will become deadly. Tumor progression critically depends on a locally permissive microenvironment, including a unique tumor-associated extracellular matrix (ECM). The ECM is a complex meshwork of proteins providing architectural support to cells and conferring biomechanical properties to tissues. ECM-derived biochemical signals transduced by cell-surface receptors, such as the integrins, regulate cellular functions such as proliferation and survival, adhesion, and migration, all essential for metastasis. Importantly, clinicians have observed that more aggressive tumors present a higher ECM content. Thus, to fully understand how tumors progress and disseminate, it is essential to study the tumor ECM. To do so, we have developed a pipeline combining bioinformatics and proteomics to comprehensively characterize the ECM composition, or "matrisome," of tissues and tumors. Using this pipeline, we demonstrated that the composition of the ECM varies i) between normal tissues and tumors, ii) between poorly and highly metastatic primary tumors, and iii) between primary tumors and derived metastases. Here we present for the first time "The Tumor ECM Atlas," a compendium of ECM proteins identified by proteomics in the microenvironment of 10+ types of primary tumors and derived metastases, including breast, colorectal and lung cancers, insulinomas and multiple myelomas, which revealed the presence of a unique subset of cancer-specific and cancer type-specific ECM proteins. We believe that this atlas is a powerful tool to formulate novel hypotheses on the roles of the ECM in tumor progression and metastasis. In addition, we propose that the ECM is an underexplored reservoir of potential diagnostic and prognostic markers and therapeutic targets, and that its exploration using proteomics will pave the way for the development of novel approaches to better care for cancer patients. Citation Format: Alexandra Naba, Karl R. Clauser, Steven A. Carr, Richard O. Hynes. Profiling the extracellular matrix landscape of tumor microenvironments using proteomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5004.
Reduced Neointima Hyperplasia of Vein Bypass Grafts in Intercellular Adhesion Molecule-1–Deficient Mice
Authors: YipingZou, YanhuaHu, ManuelMayr, HermannDietrich, GeorgWick, QingboXu
Journal: Circulation Research (2000)

Abstract—Recently, we established a new mouse model of vein graft arteriosclerosis through the grafting of vena cava to carotid arteries. In many respects, the morphological features of this murine vascular graft model resemble those of human venous bypass graft disease. With this model, we studied the role of intercellular adhesion molecule-1 (ICAM-1) in the development of vein graft arteriosclerosis in ICAM-1–deficient mice. Neointimal hyperplasia of vein grafts in ICAM-1 −/− mice was reduced 30% to 50% compared with that of wild-type control animals. Immmunofluorescent analysis revealed that increased ICAM-1 expression was observed on the endothelium and smooth muscle cells (SMCs) of the grafted veins in wild-type, but not ICAM-1 −/−, mice. MAC-1 (CD11b/18)–positive cells that adhered to the surface of vein grafts in ICAM-1 −/− mice were significantly less as identified with en face immunofluorescence, and these positive cells were more abundant in the intimal lesions of vein grafts in wild-type mice. ...
Abstract 12745: Amelioration of Mitochondrial Injury During Cardiac Resuscitation by the Combined Administration of α-Methylnorepinephrine and Zoniporide
Authors: Jeejabai Radhakrishnan, Lorissa Lamoureux, Alvin Baetiong, Raúl J Gazmuri
Journal: Circulation (2015)

Introduction: We have shown in a rat model of VF and closed-chest resuscitation that plasma levels of cytochrome c - a marker of mitochondrial injury - are inversely related to survival and both influenced by interventions that attenuate mitochondrial injury. We have also shown that administration of zoniporide (ZNP) - an NHE-1 inhibitor - combined with α-methylnorepinephrine (α-MNE) - a peripheral selective α2-adrenoreceptor agonist is highly effective for resuscitation. Hypothesis: We hypothesized that the ZNP/α-MNE combination exerts its beneficial effects partly by attenuating mitochondrial injury. Methods: VF was electrically induced in 48 male retired breeder rats and left untreated for 8 minutes. Resuscitation was attempted by 8 minutes of chest compression and delivery of electrical shocks. Rats were randomized 1:1:1:1 to receive a 3 mg/kg bolus of ZNP or 0.9% NaCl before chest compression and a 100 μg/kg bolus of α-MNE or its vehicle at minute 2 of chest compression establishing 4 groups of 12 rats each. Successfully resuscitated rats were monitored for 240 minutes. Plasma cytochrome c levels were measured by an electrochemiluminescence (ECL) immunoassay developed by us using antibodies provided in a DuoSet IC, Rat/Mouse Total Cytochrome c kit (R&amp;D systems). The ECL signal was measured using a QuickPlex SQ 120 multiplex imager from MesoScale Discovery (MSD). Results: Post-Resuscitation (PR) plasma cytochrome c levels (fold increase over baseline) were markedly attenuated in groups that received ZNP demonstrating statistical significance at PR 180 minutes (Figure). Cytochrome c levels were positively correlated with lactate levels and marginally negatively correlated with cardiac work index at PR 180 (Figure). PR lactate levels were reduced in all treatment groups with the greatest effect by the ZNP/α-MNE combination. Conclusions: We confirm that the ZNP/α-MNE combination exerts resuscitation benefits by ameliorating mitochondrial injury.
Prevention of Dystrophin-Deficient Cardiomyopathy in Twenty-One-Month-Old Carrier Mice by Mosaic Dystrophin Expression or Complementary Dystrophin/Utrophin Expression
Authors: BrianBostick, YongpingYue, ChunLong, DongshengDuan
Journal: Circulation Research (2008)

A cure for dystrophin-deficient muscular dystrophy requires treating both skeletal muscle and the heart. Whereas mosaic dystrophin expression has been shown to protect skeletal muscle, controversy exists over whether mosaic expression is protective in the heart. We have shown recently that mosaic dystrophin expression prevents stress-induced heart damage in young carrier mice. Although an interesting finding, the clinical relevance remains to be established because young dystrophin-null mdx mice do not have heart disease. On the other hand, heart failure has been reported in human carriers. To resolve this mouse/human discrepancy, we evaluated the cardiac phenotype in 21-month-old mdx, carrier, and normal mice. We found dilated cardiomyopathy in old mdx mice but not in age-matched carrier mice. All anatomical parameters and physiological assay results (ECG and closed-chest Millar catheter) were within the normal range in old carrier mice. Focal myocardial inflammation was found in a small fraction of old ...
Abstract 1728: Nonalcoholic steatohepatitis (NASH) impairs treatment of intrahepatic metastases with CD4+ T cell dependent RNA vaccine
Authors: Bernd Heinrich, Zachary J. Brown, Vormehr Mathias, Qiong Fu, Chi Ma, Su Jong Yu, Ugur Sahin, Tim F. Greten
Journal: Cancer Research (2018)

Abstract Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder in Western industrialized countries. NAFLD along with its advanced form non-alcoholic steatohepatitis (NASH) are becoming an increasing risk factor for the development of cirrhosis and subsequently for hepatocellular carcinoma (HCC). We showed a selective CD4+ T cell loss in mice fed with methionine-choline deficient (MCD) diet, a model to induce NASH (Ma et al. Nature 2016). This selective loss of CD4 T cells may not only lead to immune escape by tumor cells but also lessen the effectiveness of immunotherapy. Kreiter et al. created a RNA vaccine from B16 melanoma cells encoding the neo-epitope M30, which is presented by MHC class II and recognized by CD4+ T cells. The vaccine showed therapeutic immune response in mouse models of subcutaneous B16-tumors and lung metastases (Kreiter et al. Nature 2015). Here we present an in vivo study of M30 RNA vaccine in a mouse model of B16 melanoma liver metastasis induced by intrahepatic injection. Mice were separated into groups and fed regular chow or MCD diet. B16F10-GFP-Luc melanoma cells were intrahepatically injected and mice were treated with M30 RNA or irrelevant RNA as control via tail vein injection. Intrahepatic tumor growth was monitored by bioluminescence imaging over the course of treatment. Mice were sacrificed and immunomonitoring of tumor surrounding liver tissue and tumor infiltrating lymphocytes (TIL) was performed. Mice treated with M30 RNA vaccine showed reduced tumor growth of intrahepatic metastasis compared to irrelevant RNA. Mice fed MCD diet could not control tumor growth either receiving M30 RNA vaccine treatment or irrelevant RNA. This impaired function of the treatment was related to a loss of CD4+ T cells in the NASH liver and a more immunosuppressive immune cell phenotype in the tumor environment. This study indicates impaired efficacy of cancer immunotherapy due to fatty liver disease and subsequently changed immune response due to loss of CD4+ T cells as the main effector immune cell. As the M30 RNA vaccine reduced tumor growth in non-fatty liver, this data might be considered when planning future immunotherapy treatment strategies for comorbid patients with fatty liver disease as CD4+ T cell based treatment strategies might be impaired in patients with NASH. Citation Format: Bernd Heinrich, Zachary J. Brown, Vormehr Mathias, Qiong Fu, Chi Ma, Su Jong Yu, Ugur Sahin, Tim F. Greten. Nonalcoholic steatohepatitis (NASH) impairs treatment of intrahepatic metastases with CD4+ T cell dependent RNA vaccine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1728.
Pseudonormal Position of an Atrial Pacemaker Lead Associated With a Contralateral Pneumothorax
Authors: HirotakaYada, ToshiakiSato, KyokoSoejima, YusukeJo, MasahiroJinzaki, IkukoTogashi, HikaruNakamizo, KotaroFukumoto, KojiroTanimoto, ShunichiroMiyoshi, SachioKuribayashi, SatoshiOgawa
Journal: Circulation (2008)
Abstract 4707: Pelareorep promotes the expression of a chemokine signature that predicts response to immunotherapy
Authors: Grey A. Wilkinson, Aine Piar, Zoe Cesarz, Hue Tran, Romit Chakrabarty, Andres Gutierrez, Matt Coffey
Journal: Cancer Research (2018)

Abstract Introduction: It has been proposed that the presence of inflamed tumor phenotypes, characterized by the presence of infiltrating lymphocytes and the expression of specific chemokines and cytokines, can predict response to immunotherapy and result in better patient outcomes [1, 2]. We hypothesized that pelareorep, an immuno-oncolytic virus (IOV), may elicit predictive proinflammatory gene signatures in select cancer cell lines permissive to viral infection. Methods: Cell lines derived from non-small cell lung cancer (NSCLC, H522), colorectal cancer (CRC, SW-620), and hepatocellular carcinoma (HCC, SNU 387) were infected at an multiplicity of infection equal to 50. We examined changes in gene expression and conducted cell viability assays at 6, 12, and 18 hours post pelareorep infection (including a non-infected control). To monitor changes in gene expression we employed a custom 780-gene Pan Cancer Immune panel developed by nanoString Technologies and specifically monitored for changes in the expression of key interferon and NF-κB signalling genes, immune checkpoint ligands, and a 12-gene chemokine signature predictive of a positive response to immunotherapy identified by Messina et al. [2]. Results: All cell lines examined were susceptible to pelareorep induced cytopathic effect. Strikingly, principal component analysis revealed that the changes in gene expression were unique and different for each cell line. Of the cell lines examined, only HCC cells infected with pelareorep promoted an inflammatory signature, similar to the one used to predict response to immunotherapy in melanoma [2]. Conclusions: This study demonstrates that pelareorep can prime or promote a predictive inflamed tumor phenotype in HCC, which correlates with the innate response recently described in HCC- animal models treated with pelareorep [3]. The role of pelareorep in the treatment of hepatocellular carcinoma deserves further investigation, particularly in combination with other immunotherapies. References: [1] Gajewski, T.F., The Next Hurdle in Cancer Immunotherapy: Overcoming the Non-T-Cell-Inflamed Tumor Microenvironment. Semin Oncol, 2015. 42(4): p. 663-71. [2] Messina, J.L., et al., 12-Chemokine gene signature identifies lymph node-like structures in melanoma: potential for patient selection for immunotherapy? Sci Rep, 2012. 2: p. 765. [3] Samson, A., et al., Oncolytic reovirus as a combined antiviral and anti-tumour agent for the treatment of liver cancer. Gut, 2016. Citation Format: Grey A. Wilkinson, Aine Piar, Zoe Cesarz, Hue Tran, Romit Chakrabarty, Andres Gutierrez, Matt Coffey. Pelareorep promotes the expression of a chemokine signature that predicts response to immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4707.
Challenges and Successes in Evaluating HIV Prevention for Young Transgender Women—Building Skills, Maintaining Trust
Authors: Brittany J. Allen
Journal: JAMA Pediatrics (2018)

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 Pediatrics 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 Pediatrics journal
Abstract 1496: Different effects of lncRNA <i>NDRG1-OT1</i>_v4 fragments on regulating NDRG1 transcription in breast cancer cells under hypoxia
Authors: Chingching Yeh, Mong-Hsun Tsai, Eric Chuang, Liang-Chuan Lai
Journal: Cancer Research (2018)

Abstract Hypoxia is a crucial factor in aggressiveness of solid tumor by driving multiple signaling pathways. Recent researchers indicated that long non-coding RNA (lncRNA) could promote or inhibit tumor aggressiveness by regulating gene expression. Previous studies in our laboratory found the expression of lncRNA NDRG1-OT1_v4 significantly increased under hypoxia by next-generation sequencing (NGS). Moreover, it was discovered that the NDRG1-OT1_v4 inhibited NDRG1 at both mRNA and protein levels of NDRG1. At the protein level, NDRG1-OT1_v4 improved NDRG1 degradation via ubiquitin-mediated proteolysis pathway. However, the repressive mechanism of NDRG1 at RNA level was still unknown. In this studies, we found that NDRG1-OT1_v4 decreased the NDRG1 promoter activities when we overexpressed NDRG1-OT1_v4 under hypoxia. The fragment (150-263 nt) of NDRG1-OT1_v4 repressed NDRG1 promoter activity significantly by increasing the binding affinity of hnRNPA1. On the other hand, another fragment (264-392 nt) of NDRG1-OT1_v4 improved NDRG1 promoter activity by recruiting HIF-1 alpha. In conclusion, we found a novel mechanism that different fragments of same lncRNA could cause opposite effects on the identical target gene. Keywords: Hypoxia, LncRNA, NDRG1-OT1_v4, NDRG1, HIF-1 alpha, hnRNPA1 Citation Format: Chingching Yeh, Mong-Hsun Tsai, Eric Chuang, Liang-Chuan Lai. Different effects of lncRNA NDRG1-OT1_v4 fragments on regulating NDRG1 transcription in breast cancer cells under hypoxia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1496.
Abstract 02: BCL-W significantly contributes to B-cell lymphoma survival and development
Authors: Clare M. Adams, Ramkrishna Mitra, Jerald Z. Gong, Annette S. Kim, John K. Choi, Christine M. Eischen
Journal: Clinical Cancer Research (2017)

Abstract The ability of cells to undergo apoptosis in response to cellular stresses functions as a safeguard against tumorigenesis. Consequently, compromised apoptotic signaling must precede tumor development. To design effective therapies for cancer treatment, the underlying mechanisms that govern cell survival need to be understood. The anti-apoptotic proteins of the Bcl-2 family are key regulators of cell survival and are frequently overexpressed in malignancies, leading to increased cancer cell survival. Bcl-w, the closest anti-apoptotic relative to Bcl-2 and Bcl-xL, is essential for spermatogenesis, but was considered dispensable for other cell types. However, we recently uncovered a significant role for Bcl-w in B-cell survival and lymphomagenesis. Specifically, loss of Bcl-w conferred sensitivity to growth factor deprivation-induced B-cell apoptosis. In addition, apoptosis triggered by hyperproliferative signals from the Myc oncogene was accentuated by loss of Bcl-w. Consequences of elevated apoptosis were observed in vivo, as Bcl-w loss profoundly delayed Myc-mediated B-cell lymphoma development. We also determined Myc regulates Bcl-w expression through its transcriptional regulation of the miR-15 family. Importantly, evaluation of Burkitt lymphoma (BL) patient samples revealed BCL-W overexpression was highly selected for, and that targeting BCL-W using multiple methods induced apoptosis of BL cells. In addition, overexpression of BCL-W in BL cell lines conferred resistance to the BH3-mimetics ABT-737 and ABT-263 that inhibit anti-apoptotic BCL-2 family members. Furthermore, BCL-W was overexpressed in diffuse large B-cell lymphoma (DLBCL) and correlated with decreased patient survival. Analysis of multiple data sets of other aggressive and indolent B-cell lymphomas showed that BCL-W was frequently overexpressed in them as well. Collectively, our data indicate that BCL-W is an understudied contributor to B-cell lymphoma development and survival that appears to be as important as BCL-2 to B-cell lymphomas. In addition, BCL-W is a predictive biomarker that could improve prognostication and the development of more effective treatment strategies for B-cell lymphomas. Citation Format: Clare M. Adams, Ramkrishna Mitra, Jerald Z. Gong, Annette S. Kim, John K. Choi, Christine M. Eischen. BCL-W significantly contributes to B-cell lymphoma survival and development [abstract]. In: Proceedings of the Second AACR Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; May 6-9, 2017; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(24_Suppl):Abstract nr 02.
Procoagulant Soluble Tissue Factor Is Released From Endothelial Cells in Response to Inflammatory Cytokines
Authors: BjörnSzotowski, SilvioAntoniak, WolfgangPoller, Heinz-PeterSchultheiss, UrsulaRauch
Journal: Circulation Research (2005)

Inflammatory cytokines alter the hemostatic balance of endothelial cells (ECs). Alternatively spliced human tissue factor (asHTF), a soluble isoform of tissue factor (TF), has recently been detected in ECs, possibly contributing to procoagulability. Agonists regulating asHTF expression and release are yet unknown. This study examines the effect of TNF-α and IL-6 on the endothelial expression of both TF variants and delineates the impact of asHTF on the procoagulability of extracellular fluids. asHTF and TF mRNA were assessed by real-time PCR, and asHTF, TF, and tissue factor pathway inhibitor (TFPI) proteins by Western blot and fluorescence microscopy before and after stimulation with TNF-α (10 ng/mL) or IL-6 (10 ng/L). The procoagulability of cell supernatant was analyzed by a chromogenic assay with or without phospholipid vesicles. We found asHTF mRNA to be maximally increased 10 minutes after TNF-α and 40 minutes after IL-6 treatment (asHTF/GAPDH ratio 0.0223±0.0069 versus 0.0012±0.0006 for control, P<...
Abstract LB-304: Customizable, <i>in vitro</i> protein glycosylation for antibacterial and anti-cancer vaccines
Authors: Jessica C. Stark, Thapakorn Jaroentomeechai, Rachel S. Dubner, Karen J. Hsu, Cameron Glasscock, Matthew P. DeLisa, Michael C. Jewett
Journal: Cancer Research (2018)

Abstract Changes in protein glycosylation are important hallmarks of cancer biology, serving as biomarkers for cancer progression and predictors of cancer prognosis. Moreover, tumor-associated carbohydrate antigens (TACAs) provide potential targets for therapeutic and prophylactic interventions. However, development of anti-cancer immunotherapies and vaccines directed against TACAs has been limited due to the significant challenges associated with synthesizing proteins bearing defined glycan structures in vivo. These challenges arise due to the complex, non-templated nature of the glycosylation process and the inability to control glycosylation components at precise ratios in living cells. To address these challenges, we describe a novel cell-free glycoprotein synthesis (CFGpS) technology that seamlessly integrates protein biosynthesis with asparagine-linked (N-linked) protein glycosylation. The platform is flexible and modular, allowing the decoration of proteins with structurally diverse, yet homogeneous glycans, including the eukaryotic trimannosyl N-glycan (mannose3-N-acetylglucosamine2, Man3GlcNAc2), which forms the core of all tumor-associated N-glycans. We demonstrate the utility of this platform through the production of antibacterial glycoconjugate vaccines directed against the highly infectious pathogenic bacterium Franciscella tularensis. Importantly, we are able to synthesize and glycosylate a variant of E. coli maltose binding protein (MBP) that has been shown to elicit humoral and cell-based immunity to polysaccharide antigens in mice. Our work demonstrates a novel approach for the customizable glycosylation of immunogenic proteins with TACAs in a cell-free system. The ability of the CFGpS platform to synthesize defined glycan structures uniquely enables the production of novel antibacterial and anti-cancer vaccines. Citation Format: Jessica C. Stark, Thapakorn Jaroentomeechai, Rachel S. Dubner, Karen J. Hsu, Cameron Glasscock, Matthew P. DeLisa, Michael C. Jewett. Customizable, in vitro protein glycosylation for antibacterial and anti-cancer vaccines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-304.