tbuckley/cabot-search huggingface dataset:
15-Deoxy-Δ12, 14-prostaglandin J2 up-regulates VEGF and MMP-1 via Nrf2-mediated heme oxygenase-1 induction in human breast cancer cells
Authors: Eun-Hee Kim, Jung-Hyun Kim, Hye-Kyung Na, Young-Joon Surh
Journal: Cancer Research (2007)

3466  Elevated expression or activity of heme oxygenase-1 (HO-1), a ubiquitous stress-responsive enzyme, has been reported to stimulate proliferation and to accelerate angiogenesis and metastasis in several types of tumor cells. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), an endogenous ligand of peroxisome proliferator-activated receptor γ, has been known to induce HO-1 in certain cell lines. In the present work, we found that treatment of human breast cancer (MCF-7) cells with nontoxic doses of 15d-PGJ2 (3-30 μM) led to concentration- and time-dependent increases in the expression and activity of HO-1. The induction of HO-1 expression preceded the up-regulation of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-1 (MMP-1). The up-regulation of VEGF and MMP-1 expression by 15d-PGJ2 was abrogated by pharmacological inhibition with zinc protophophyrin (ZnPP) or si-RNA knock down of HO-1. Moreover, ZnPP decreased the in vitro capillary formation induced by 15d-PGJ2 in human umbilical vein endothelial cells. Likewise, ZnPP treatment inhibited the migrative phenotype of 15d-PGJ2-treated MCF-7 cells as determined by the wound migration assay. In another experiment using luciferase reporter constructs containing different segments of promoter, the 15d-PGJ2-induced expression of HO-1 was found to be primarily governed by the distal enhancers (E1 and E2), which harbour three canonical ARE-like stress-responsive elements (StRE). Nrf2, a basic-leucine zipper transcription factor, plays a key role in regulating the antioxidant response element (ARE)-driven up-regulation of antioxidant enzymes including HO-1. 15d-PGJ2 treatment elevated nuclear translocation and subsequent ARE binding of Nrf2. MCF-7 cells transfected with dominant negative Nrf2 and Nrf2 si-RNA were less responsive to 15d-PGJ2 in terms of inducing expression of HO-1 and VEGF. Biotinylated 15d-PGJ2 bound to Keap1, a cytoplasmic repressor of Nrf2, which was confirmed by avidin pull-down. In contrast to 15d-PGJ2, 9,10-dihydro-15d-PGJ2 lacking an electrophilic α,β-unsaturated carbonyl moiety failed to activate Nrf2 and induce HO-1. Taken together, these results suggest that 15d-PGJ2 containing an electrophilic cyclopentenone moiety can covalently modify Keap1, presumably at the critical cysteine residue, thereby facilitating the dissociation of Nrf2 from this inhibitory protein. 15d-PGJ2-induced expression of HO-1 via the Nrf2 signaling may be implicated in angiogenesis and metastasis in human breast cancer.
Sustained Release of TPCA‐1 from Silk Fibroin Hydrogels Preserves Keratocyte Phenotype and Promotes Corneal Regeneration by Inhibiting Interleukin‐1<i>β</i> Signaling
Authors: Wei Zhang, Jialin Chen, Mingli Qu, Ludvig J. Backman, Aini Zhang, Haoyang Liu, Xiaoping Zhang, Qingjun Zhou, Patrik Danielson
Journal: Advanced Healthcare Materials (2020)

Abstract Corneal injury due to ocular trauma or infection is one of the most challenging vision impairing pathologies that exists. Many studies focus on the pro‐inflammatory and pro‐angiogenic effects of interleukin‐1 β (IL‐1 β ) on corneal wound healing. However, the effect of IL‐1 β on keratocyte phenotype and corneal repair, as well as the underlying mechanisms, is not clear. This study reports, for the first time, that IL‐1 β induces phenotype changes of keratocytes in vitro, by significantly down‐regulating the gene and protein expression levels of keratocyte markers (Keratocan, Lumican, Aldh3a1 and CD34). Furthermore, it is found that the NF‐ κ B pathway is involved in the IL‐1 β ‐induced changes of keratocyte phenotype, and that the selective IKK β inhibitor TPCA‐1, which inhibits NF‐ κ B, can preserve keratocyte phenotype under IL‐1 β simulated pathological conditions in vitro. By using a murine model of corneal injury, it is shown that sustained release of TPCA‐1 from degradable silk fibroin hydrogels accelerates corneal wound healing, improves corneal transparency, enhances the expression of keratocyte markers, and supports the regeneration of well‐organized epithelium and stroma. These findings provide insights not only into the pathophysiological mechanisms of corneal wound healing, but also into the potential development of new treatments for patients with corneal injuries.
Role of R-spondin 2 in arterial lymphangiogenesis and atherosclerosis
Authors: Bhupesh Singla, Hui-Ping Lin, Alex Chen, WonMo Ahn, Pushpankur Ghoshal, Mary Cherian-Shaw, Joseph White, Brian K Stansfield, Gábor Csányi
Journal: Cardiovascular Research (2020)

Impaired lymphatic drainage of the arterial wall results in intimal lipid accumulation and atherosclerosis. However, the mechanisms regulating lymphangiogenesis in atherosclerotic arteries are not well understood. Our studies identified elevated levels of matrix protein R-spondin 2 (RSPO2) in atherosclerotic arteries. In this study, we investigated the role of RSPO2 in lymphangiogenesis, arterial cholesterol efflux into lesion-draining lymph nodes (LNs) and development of atherosclerosis.
Viral Vectors for Neural Circuit Mapping and Recent Advances in Trans-synaptic Anterograde Tracers
Authors: Xiangmin Xu, Todd C. Holmes, Min-Hua Luo, Kevin T. Beier, Gregory D. Horwitz, Fei Zhao, Wenbo Zeng, May Hui, Bert L. Semler, Rozanne M. Sandri-Goldin
Journal: Neuron (2020)
The Effect of Conditioning Regimen Dose Reduction in Obese Patients Undergoing Autologous Transplantation
Authors: Claudio G Brunstein, Marcelo C. Pasquini, Soyoung Kim, Mingwei Fei, Andrew Artz, Minoo Battiwalla, Nelli Bejanyan, Robert Peter Gale, Peiman Hematti, Oscar Boutros Lahoud, Marcos De Lima, Ran Reshef, Seth J Rotz, Bipin N. Savani, Harry C. Schouten, Shin Mineishi, John Rogosheske, Miguel-Angel Perales
Journal: Blood (2017)
Covid-19 and ethnic minorities: the Public Health England report distracts from proactive and timely intervention
Authors: Jayshree Pillaye
Journal: BMJ (2020)

I disagree with Khunti and colleagues that the report by Public Health England (PHE) on the impact of covid-19 on black, Asian, and minority ethnic (BAME) groups was “limited in its recommendations, albeit broad in its scope.”12 The recommendations were generic with recycling and reframing of previous PHE publications.

The report failed its remit to suggest ways to reduce disparities in …
Abstract PR14: Ewing sarcoma cells exploit the IL1RAP-CTH axis to drive oxidative stress adaptation and lung metastasis
Authors: Haifeng Zhang, Amal M. El-Naggar, Hongwei Cheng, Alberto Delaidelli, Gian Luca Negri, Wei Li, Dimiter S. Dimitrov, Poul H.B. Sorensen
Journal: Cancer Research (2020)

Abstract Metastasis is a highly inefficient process due to the high oxidative stress that cancer cells experience, such as in the circulation and at distant organs prior to colonization. How cancer cells adapt to those stressful conditions and develop anti-anoikis properties remains elusive. Here our global translatome and proteome analyses have uncovered novel signatures exploited by oncogene-transformed cells to adapt and survive anoikis-inducing stress. We reveal that EWS-ETS chimeric oncoproteins trigger the expression of the IL1RAP surface protein to alleviate oxidative stress and facilitate stress adaptation, thereby promoting lung metastasis in Ewing sarcoma. Proteomic profiling identifies CTH, a key enzyme for de novo cysteine synthesis and redox regulation, as an important functional downstream mediator of IL1RAP. Blockade of either IL1RAP or CTH, using genetic or pharmacologic approaches, renders EWS cells susceptible to oxidative stress in vitro, and dramatically mitigates primary tumor growth, local invasion and lung metastasis in mice. Importantly, high expression of this IL1RAP-CTH axis correlates with markedly decreased overall and event-free survival in EWS patients. Thus, our study has defined a novel mechanism exploited by EWS cells for metastasis, which can be a potential therapeutic target for high-risk metastatic EWS. This abstract is also being presented as Poster B58. Citation Format: Haifeng Zhang, Amal M. El-Naggar, Hongwei Cheng, Alberto Delaidelli, Gian Luca Negri, Wei Li, Dimiter S. Dimitrov, Poul H.B. Sorensen. Ewing sarcoma cells exploit the IL1RAP-CTH axis to drive oxidative stress adaptation and lung metastasis [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr PR14.
Osteogenic and Adipogenic Differentiation of Mesenchymal Stem Cells in Gelatin Solutions of Different Viscosities
Authors: Kyubae Lee, Yazhou Chen, Toru Yoshitomi, Naoki Kawazoe, Yingnan Yang, Guoping Chen
Journal: Advanced Healthcare Materials (2020)

Abstract Accumulating evidence indicates that stem cell fate can be regulated by mechanical properties of the extracellular matrix. Most studies have focused onthe influence of matrix elasticity and viscoelasticity on stem cell differentiation. However, how matrix viscosity affects stem cell differentiation has been overlooked. In this study, a biphasic gelatin solution/hydrogel system is used for 3D culture of human bone marrow–derived mesenchymal stem cells (MSCs) to investigate the influence of gelatin solution viscosity on simultaneous osteogenic and adipogenic differentiation at the same culture condition. Gelatin solution promotes cell proliferation, while its promotive effect decreases with the increase of viscosity. The influence of viscosity on osteogenic and adipogenic differentiation of MSCs shows opposite trends. A high‐viscosity gelatin solution results in an increase of alkaline phosphatase (ALP) activity, calcium deposition, and expression of osteogenesis‐related genes. On the other hand, in a low‐viscosity gelatin solution, a lot of lipid vacuoles are formed and adipogenesis‐related genes are highly expressed. The results indicate high viscosity is beneficial for osteogenic differentiation, while low viscosity is beneficial for adipogenic differentiation. These findings suggest the importance of matrix viscosity on stem cell differentiation in 3D microenvironments.
A recombinant oncolytic Newcastle virus expressing MIP-3α promotes systemic antitumor immunity
Authors: Feng-Ying Huang, Jin-Yan Wang, Shu-Zhen Dai, Ying-Ying Lin, Yan Sun, Liming Zhang, Zhuoxuan Lu, Rong Cao, Guang-Hong Tan
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background The oncolytic Newcastle disease virus (NDV) is inherently able to trigger the lysis of tumor cells and induce the immunogenic cell death (ICD) of tumor cells and is also an excellent gene-engineering vector. The macrophage inflammatory protein-3α (MIP-3α) is a specific chemokine for dendritic cells (DCs). Thus, we constructed a recombinant NDV expressing MIP-3α (NDV-MIP3α) as an in vivo DC vaccine for amplifying antitumor immunities. Methods The recombinant NDV-MIP3α was constructed by the insertion of MIP-3α cDNA between the P and M genes. Western blotting assay and ELISA were used to detect MIP-3α, HMGB1, IgG, and ATP in the supernatant and sera. The chemotaxis of DCs was examined by Transwell chambers. The phenotypes of the immune cells (eg, DCs) were analyzed by flow cytometry. The antitumor efficiency of NDV-MIP3α was observed in B16 and CT26 tumor-bearing mice. Immunofluorescence and immunohistochemistry were applied to observe the ecto-calreticulin (CRT) and intratumoral attraction of DCs. Adoptive transfer of splenocytes and antibodies and depletion of T-cell subsets were used to evaluate the relationship between antitumor immunities and the role of the T-cell subtype. Results The findings show that NDV-MIP3α has almost the same capabilities of tumor lysis and induction of ICD as the wild-type NDV (NDV-WT). MIP-3α secreted by NDV-MIP3α could successfully attract DCs in vitro and in vivo. Both B16 and CT26 cells infected with NDV-MIP3α could strongly promote DC maturation and activation. Compared with NDV-WT, intratumoral injection of NDV-MIP3α and the adoptive transfer of T lymphocytes from mice injected with NDV-MIP3α resulted in a significant suppression of B16 and CT26 tumor growth. The NDV-MIP3α-induced production of tumor-specific cellular and humoral immune responses was dependent on CD8 + T cells and partially on CD4 + T cells. A significant reversion of tumor microenvironments was found in the mice injected with NDV-MIP3α. Conclusions Compared with NDV-WT, the recombinant NDV-MIP3α as an in vivo DC vaccine demonstrates enhanced antitumor activities through the induction of stronger system immunities and modulation of the tumor microenvironment. This strategy may be a potential approach for the generation of an in vivo DC vaccine.
Estimating the impact of treatment and imaging modalities on 5-year net survival of 11 cancers in 200 countries: a simulation-based analysis
Authors: Zachary J Ward, Andrew M Scott, Hedvig Hricak, May Abdel-Wahab, Diana Paez, Miriam Mikhail Lette, H Alberto Vargas, T Peter Kingham, Rifat Atun
Journal: The Lancet Oncology (2020)
Prognostic Value of Quantitative Metrics From Positron Emission Tomography in Ischemic Heart Failure
Authors: Dominik C. Benz, Philippe A. Kaufmann, Elia von Felten, Georgios Benetos, Georgios Rampidis, Michael Messerli, Andreas A. Giannopoulos, Tobias A. Fuchs, Christoph Gräni, Catherine Gebhard, Aju P. Pazhenkottil, Andreas J. Flammer, Philipp A. Kaufmann, Ronny R. Buechel
Journal: JACC. Cardiovascular imaging (2020)
All Myeloid-Derived Suppressor Cells Are Not Created Equal: How Gender Inequality Influences These Cells and Affects Cancer Therapy
Authors: Dmitry I. Gabrilovich
Journal: Cancer Discovery (2020)

Abstract Summary: In this issue of Cancer Discovery, Bayik and colleagues demonstrated sexual dimorphism in accumulation of different populations of myeloid-derived suppressor cells in glioblastoma and showed that they could be targeted by different agents. See related article by Bayik et al., p. 1210.
Myelodysplastic syndromes: 2021 update on diagnosis, risk stratification and management
Authors: Guillermo Garcia‐Manero, Kelly S. Chien, Guillermo Montalban‐Bravo
Journal: American Journal of Hematology (2020)

Abstract Disease overview The myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). Myelodysplastic syndromes occur more frequently in older males and in individuals with prior exposure to cytotoxic therapy. Diagnosis Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry and molecular genetics is usually complementary and may help refine diagnosis. Risk‐stratification Prognosis of patients with MDS can be calculated using a number of scoring systems. In general, all these scoring systems include analysis of peripheral cytopenias, percentage of blasts in the bone marrow and cytogenetic characteristics. The most commonly accepted system is the Revised International Prognostic Scoring System (IPSS‐R). Somatic mutations can help define prognosis and therapy. Risk‐adapted therapy Therapy is selected based on risk, transfusion needs, percent of bone marrow blasts, cytogenetic and mutational profiles, comorbidities, potential for allogeneic stem cell transplantation (alloSCT) and prior exposure to hypomethylating agents (HMA). Goals of therapy are different in lower‐risk patients than in higher‐risk individuals and in those with HMA failure. In lower‐risk MDS, the goal is to decrease transfusion needs and transformation to higher risk disease or AML, as well as to improve survival. In higher‐risk disease, the goal is to prolong survival. In 2020, we witnessed an explosion of new agents and investigational approaches. Current available therapies include growth factor support, lenalidomide, HMAs, intensive chemotherapy and alloSCT. Novel therapeutics approved in 2020 are luspatercept and the oral HMA ASTX727. At the present time, there are no approved interventions for patients with progressive or refractory disease particularly after HMA‐based therapy. Options include participation in a clinical trial, cytarabine‐based therapy or alloSCT.
Identification of occult cerebral microbleeds in adults with immune thrombocytopenia
Authors: Nichola Cooper, Melanie A. Morrison, Camelia Vladescu, Alice C. J. Hart, Deena Paul, Amna Malik, Thomas Young, Asad Luqmani, Maria Atta, David J. Sharp, James B. Bussel, Adam D. Waldman
Journal: Blood (2020)
Transvenous or Subcutaneous ICD — Similar but Different
Authors: Mark S. Link, Jose A. Joglar
Journal: New England Journal of Medicine (2020)

The results of the long-awaited Prospective Randomized Comparison of Subcutaneous and Transvenous Implantable Cardioverter Defibrillator Therapy (PRAETORIAN) trial — a randomized, controlled trial comparing transvenous implantable cardioverter–defibrillators (ICDs) with subcutaneous ICDs — are reported in this issue of the Journal.1 The transvenous ICD, developed in the 1980s, is implanted in the prepectoral area with the use of a transvenous lead that is inserted through the axillary or subclavian vein and advanced to the right ventricle. Randomized, controlled trials in the 1990s2,3 showed a significant survival benefit in patients who had these devices implanted after cardiac arrest because of sustained ventricular . . .
Abstract 15917: Oscar 2 and Spacelabs 90207/90217 Ambulatory Blood Pressure Monitors Misclassify Patients Based on New American Heart Association Guidelines
Authors: V P Lombardi, Patrick C Reichhold, Jennifer L Cramer, Hannah P Harkness, Natalie J DeBell, Nicholas R Dietz, Donald L Pate
Journal: Circulation (2019)

Purpose & Hypothesis: We used our Dual Monitor Protocol to determine the accuracy of oscillometric ambulatory blood pressure monitors (ABPMs), the Oscar 2 and Spacelabs 90207/90217 predicting they ...
Human Brown Adipocyte Thermogenesis Is Driven by β2-AR Stimulation
Authors: Denis P. Blondin, Soren Nielsen, Eline N. Kuipers, Mai C. Severinsen, Verena H. Jensen, Stéphanie Miard, Naja Z. Jespersen, Sander Kooijman, Mariëtte R. Boon, Mélanie Fortin, Serge Phoenix, Frédérique Frisch, Brigitte Guérin, Éric E. Turcotte, François Haman, Denis Richard, Frédéric Picard, Patrick C.N. Rensen, Camilla Scheele, André C. Carpentier
Journal: Cell Metabolism (2020)
Abstract B01: Alternative splicing as a therapeutic vulnerability in pediatric rhabdomyosarcoma
Authors: Safiya Khurshid, Matias Montes, Ryan Roberts, Frank Rigo, Dawn S. Chandler
Journal: Cancer Research (2020)

Abstract Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue sarcoma, and children who present with metastatic disease at the time of diagnosis have a poor prognosis and survival rate. The molecular events distinguishing these tumors are poorly understood. Comprehensive genetic analysis of pediatric RMS samples has revealed that these tumors are “quiet” at the genomic level and have a relatively low mutation rate. Thus, we have turned our attention to the RMS spliceome, the alternatively or aberrantly spliced transcripts, to identify new therapeutic targets. Indeed, recent advances in high-throughput sequencing technologies have uncovered a surprising number of alternatively spliced variants associated with tumorigenesis, implicating regulated splicing in the tumor phenotype. We hypothesize that differentially spliced isoforms provide a novel opportunity to modulate splicing as a therapeutic intervention in these cancers. We have identified two major splicing networks that are altered in response to tumor specific physiologic changes in RMS. We have identified RNA binding protein and their specific cis-regulatory sequence binding sites that control the splicing changes. In collaboration with Ionis Pharmaceuticals, we have designed splice-switching oligonucleotides that target the specific sequences in the pre-mRNA transcript to occlude protein binding and engineer splicing away from the tumorigenic isoforms. The splice switching oligonucleotides (SSOs) have been successful in targeting the desired transcripts to change the splice isoform, repressing RMS cell growth, and preventing migration, invasion, and angiogenesis. We are currently testing the SSOs in RMS xenograft models as well as in genetically engineered mice to assess their efficacy in vivo. Our long-term goal is to understand the role of alternative splicing in cancer and to target pre-mRNA splicing pathway as a therapeutic intervention point. From these studies, we expect to better understand the cellular events that activate alternative splicing in the pathway to tumorigenesis and how to target transcripts for therapeutic benefit in the future. Furthermore, our findings implement a new splice-modulating paradigm for cancer treatment and pioneer a strategy that may be applied throughout the spliceome to treat cancer and provide a new avenue of rational therapy design. Citation Format: Safiya Khurshid, Matias Montes, Ryan Roberts, Frank Rigo, Dawn S. Chandler. Alternative splicing as a therapeutic vulnerability in pediatric rhabdomyosarcoma [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B01.
Hematopoietic, Immune Recovery and Outcomes after Autologous Stem Cell Transplantation Following Plerixafor Plus G-CSF Versus Chemotherapy and G-CSF Based Mobilization in Pediatric Patients
Authors: Jung Yoon Choi, Hyoung Jin Kang, Kyung Taek Hong, Che Ry Hong, Kyung Duk Park, Hee Young Shin
Journal: Blood (2017)
Abstract IA27: Patient-derived organoids in pediatric cancer research
Authors: Camilla Calandrini, Frans Schutgens, Rurika Oka, Thanasis Margaritis, Tito Candelli, Luka Mathijsen, Carola Ammerlaan, Ravian van Ineveld, Sepideh Derakhshan, Lars Custers, Philip Lijnzaad, Harry Begthel, Hinri Kerstens, Maarten Rookmaker, Marianne Verhaar, Patrick Kemmeren, Ronald de Krijger, Kathy Pritchard-Jones, Anne Rios, Marry van den Heuvel-Eibrink, Frank Holstege, Ruben van Boxtel, Hans Clevers, Jarno Drost
Journal: Cancer Research (2020)

Abstract Recent advances in in vitro culture technologies, such as adult stem cell-derived organoids, have opened up new avenues for the development of novel, more physiologic human cancer models. Such preclinical models are essential for efficient translation of basic cancer research into novel treatment regimens. We succeeded in growing organoids from a range of pediatric solid tumors, including Wilms’ tumors, renal cell carcinomas, and different types of rhabdoid tumors (i.e., AT/RT, MRT). Tumor organoids retain many characteristics of parental tumor tissue. For instance, Wilms’ tumor organoids retain the cellular heterogeneity of tumors, as they are composed of an intricate network of different cell types. Moreover, we demonstrate that tumor organoids are amenable to gene editing and high-throughput drug screens. In conclusion, our pediatric cancer organoids capture disease and tissue heterogeneity and provide a platform for basic cancer research, drug screening, and personalized medicine. Citation Format: Camilla Calandrini, Frans Schutgens, Rurika Oka, Thanasis Margaritis, Tito Candelli, Luka Mathijsen, Carola Ammerlaan, Ravian van Ineveld, Sepideh Derakhshan, Lars Custers, Philip Lijnzaad, Harry Begthel, Hinri Kerstens, Maarten Rookmaker, Marianne Verhaar, Patrick Kemmeren, Ronald de Krijger, Kathy Pritchard-Jones, Anne Rios, Marry van den Heuvel-Eibrink, Frank Holstege, Ruben van Boxtel, Hans Clevers, Jarno Drost. Patient-derived organoids in pediatric cancer research [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr IA27.