8 research outputs found
Pulmonary Hemorrhage Secondary to Aortobronchial Fistula Occurring Soon after the Placement of an Endovascular Stent for a Thoracic Aortic Aneurysm
No full text[No abstract available]Appoo JJ, 2006, J THORAC CARDIOV SUR, V131, P1087, DOI 10.1016-j.jtcvs.2005.12.058; Brandt M, 2005, EUR J VASC ENDOVASC, V30, P365, DOI 10.1016-j.ejvs.2005.04.005; Jacobs TS, 2003, J VASC SURG, V37, P16, DOI 10.1067-mva.2003.58; Trocciola SA, 2006, J VASC SURG, V43, P109, DOI 10.1016-j.jvs.2005.09.023; VonFricken K, 2000, ANN THORAC SURG, V70, P1407, DOI 10.1016-S0003-4975(00)01683-00
The H19 Long non-coding RNA in cancer initiation, progression and metastasis – a proposed unifying theory
No full textThe H19 non-coding RNA is essential for human tumor growth.
No full textBackgroundMutations and epigenetic aberrant signaling of growth factors pathways contribute to carcinogenesis. Recent studies reveal that non-coding RNAs are controllers of gene expression. H19 is an imprinted gene that demonstrates maternal monoallelic expression without a protein product; although its expression is shut off in most tissues postnatally, it is re-activated during adult tissue regeneration and tumorigenesis. Moreover, H19 is highly expressed in liver metastasis derived from a range of carcinomas. The objective of this study is to explore the role of H19 in carcinogenesis, and to determine its identification as an anti-tumor target.Methodology/principle findingsBy controlling oxygen pressure during tumor cell growth and H19 expression levels, we investigated the role of H19 expression in vitro and in vivo in hepatocellular (HCC) and bladder carcinoma. Hypoxia upregulates the level of H19 RNA. Ablations of tumorigenicity of HCC and bladder carcinomas in vivo are seen by H19 knockdown which also significantly abrogates anchorage-independent growth after hypoxia recovery, while ectopic H19 expression enhances tumorigenic potential of carcinoma cells in vivo. Knocking-down H19 message in hypoxic stress severely diminishes p57(kip2) induction. We identified a number of potential downstream targets of H19 RNA, including angiogenin and FGF18.ConclusionsH19 RNA harbors pro-tumorigenic properties, thus the H19 gene behaves as an oncogene and may serve as a potential new target for anti-tumor therapy
The oncofetal H19 RNA connection: Hypoxia, p53 and cancer
No full textAbstractExpression of the imprinted H19 gene is remarkably elevated in a large number of human cancers. Recently, we reported that H19 RNA is up-regulated in hypoxic stress and furthermore, it possesses oncogenic properties. However, the underlying mechanism(s) of these phenomena remain(s) unknown. Here we demonstrate a tight correlation between H19 RNA elevation by hypoxia and the status of the p53 tumor suppressor. Wild type p53 (p53wt) prevents the induction of H19 upon hypoxia, and upon its reconstitution in p53null cells. The last case is accompanied by a decrease in cell viability. The p53 effect is nuclear and seems independent of its tetramerization. Furthermore, using knockdown and over-expression approaches we identified HIF1-α as a critical factor that is responsible for H19 induction upon hypoxia. Knocking down HIF1-α abolishes H19 RNA induction, while its over-expression significantly enhances the H19 elevation in p53null hypoxic cells. In p53wt hypoxic cells simultaneous suppression of p53 and over-expression of HIF1-α are needed to induce H19 significantly, while each treatment separately resulting in a mild induction, indicating that the molecular mechanism of p53 suppression effect on H19 may at least in part involve interfering with HIF1-α activity. In vivo a significant increase in H19 expression occurred in tumors derived from p53null cells but not in p53wt cells. Taken together, our results indicate that a functional link exists between p53, HIF1-α and H19 that determines H19 elevation in hypoxic cancer cells. We suggest that this linkage plays a role in tumor development
Oncofetal H19 RNA promotes tumor metastasis
No full textAbstractThe oncofetal H19 gene transcribes a long non-coding RNA(lncRNA) that is essential for tumor growth. Here we found that numerous established inducers of epithelial to mesenchymal transition(EMT) also induced H19/miR-675 expression. Both TGF-β and hypoxia concomitantly induced H19 and miR-675 with the induction of EMT markers. We identified the PI3K/AKT pathway mediating the inductions of Slug, H19 RNA and miR-675 in response to TGF-β treatment, while Slug induction depended on H19 RNA. In the EMT induced multidrug resistance model, H19 level was also induced. In a mouse breast cancer model, H19 expression was tightly correlated with metastatic potential. In patients, we detected high H19 expression in all common metastatic sites tested, regardless of tumor primary origin. H19 RNA suppressed the expression of E-cadherin protein. H19 up-regulated Slug expression concomitant with the suppression of E-cadherin protein through a mechanism that involved miR-675. Slug also up-regulated H19 expression and activated its promoter. Altogether, these results may support the existence of a positive feedback loop between Slug and H19/miR-675, that regulates E-cadherin expression. H19 RNA enhanced the invasive potential of cancer cells in vitro and enhanced tumor metastasis in vivo. Additionally, H19 knockdown attenuated the scattering and tumorigenic effects of HGF/SF. Our results present novel mechanistic insights into a critical role for H19 RNA in tumor progression and indicate a previously unknown link between H19/miR-675, Slug and E-cadherin in the regulation of cancer cell EMT programs
Conventional versus advanced imaging selection for endovascular treatment of basilar artery occlusion strokes
No full textFunding Information: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Chen: None. Dr Colasurdo: None. Dr Matsukawa received a lecture fee from Daiichi-Sankyo and Stryker and consulting services fee from B. Braun. Dr Al Kasab: grant from Stryker for RESCUE-ICAS registry. Dr Cunningham: None. Dr Maier: Speakers honoraria from Pfizer and Bristol-Myers Squibb. Dr Jabbour: None. Dr Kim: None. Dr Wolfe: None. Dr Rai: None. Dr Starke: RMS research is supported by the NREF, Joe Niekro Foundation, Brain Aneurysm Foundation, Bee Foundation, Department of Health Biomedical Research Grant (21K02AWD-007000), and by National Institute of Health (R01NS111119-01A1) and (UL1TR002736, KL2TR002737) through the Miami Clinical and Translational Science Institute, from the National Center for Advancing Translational Sciences and the National Institute on Minority Health and Health Disparities. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. RMS has an unrestricted research grant from Medtronic and Balt and has consulting and teaching agreements with Penumbra, Abbott, Medtronic, Balt, InNeuroCo, Cerenovus, Naglreiter, Tonbridge, Von Medical, and Optimize Vascular. Dr Psychogios: Grants from the Swiss National Science Foundation (SNF) for the DISTAL trial (33IC30_198783) and TECNO trial (32003B_204977), Grant from Bangerter-Rhyner Stiftung for the DISTAL trial. Unrestricted Grants for the DISTAL trial from Stryker Neurovascular Inc., Phenox GmbH, Penumbra Inc. and Rapid Medical Inc., Sponsor-PI SPINNERS trial (Funded by a Siemens Healthineers AG Grant), Research agreement with Siemens Healthineers AG, Local PI for the ASSIST, EXCELLENT, TENSION, COATING, SURF, and ESCAPE-NEXT trials. Speaker fees: Stryker Neurovascular Inc., Medtronic Inc., Penumbra Inc., Acandis GmbH, Phenox GmbH, Siemens Healthineers AG. Dr Samaniego: None. Dr Arthur: Consultant for Arsenal, Balt, Johnson and Johnson, Medtronic, Microvention, Penumbra, Perfuze, Scientia, Siemens, Stryker. Research support from Balt, Medtronic, Microvention, Penumbra, and Siemens. Shareholder Azimuth, Bendit, Cerebrotech, Endostream, Magneto, Mentice, Neurogami, Neuros, Perfuze, Revbio, Scientia, Serenity, Synchron, Tulavi, Vastrax, VizAI. Dr Yoshimura received a lecture fee from Stryker, Medtronic, Johnson & Johnson, Kaneka Medics. Dr Cuellar: Dr Hugo Cuellar: Consultant for Medtronic, Penumbra and Microvention. Dr Grossberg: None. Dr Alawieh: None. Dr Tanweer: None. Dr Mascitelli: None. Dr Fragata: None. Dr Polifka: None. Dr Osbun: None. Dr Crosa: None. Dr Matouk: Consultant for Stryker, Medtronic, Microvention, Penumbra, and Silk Road Medical. Speaker for Penumbra and Silk Road Medical. Contact PI for NIH Grant R21NS128641. Dr Park: Consultant for Medtronic. Dr Levitt: Unrestricted educational grants from Medtronic and Stryker; consulting agreement with Medtronic, Aeaean Advisers and Metis Innovative; equity interest in Proprio, Stroke Diagnostics, Apertur, Stereotaxis, Fluid Biomed, and Hyperion Surgical; editorial board of Journal of NeuroInterventional Surgery, data safety monitoring board of Arsenal Medical. Dr Brinjikji: None. Dr Moss: None. Dr Dumont: None. Dr Williamson: Consultant for Medtronic, Stryker, and Synaptive Medical. Dr Navia: Consultant for Penumbra, Medtronic, Stryker, Cerenovus, and Balt. Dr Leacy: Research grants from Siemens Healthineers and Kaneka medical. Consultant for Cerenovus, Stryker Neurovascular and Scientia Vascular. Minor equity interest Vastrax, Borvo medical, Synchron, Endostream, Von Vascular. Dr Chowdhry: Consultant and proctor for Medtronic and Microvention. Dr Ezzeldin: Speaker for Viz.ai and has stocks in Galaxy Therapeutics. Dr Spiotta: Research support from Penumbra, Stryker, Medtronic, and RapidAI. Consultant for Penumbra, Stryker, Terumo, and RapidAI. Dr Kan: Grants from the NIH (1U18EB029353-01) and unrestricted educational grants from Medtronic and Siemens. Consultant for Imperative Care and Stryker Neurovascular. Stock ownership in Vena Medical. Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The STAR registry receives research support from Penumbra, Microvention, Medtronic, Stryker, RapidAI, Brain Aneurysm Foundation. Publisher Copyright: © European Stroke Organisation 2025. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).Introduction: Endovascular thrombectomy (EVT) is an effective treatment for basilar artery occlusion (BAO) stroke in select patients. While there is a growing body of literature suggesting that advanced imaging modalities such as computed tomography perfusion (CTP) and magnetic resonance (MR) may not be necessary for selecting anterior circulation large vessel occlusion stroke patients for EVT, whether advanced imaging may be superior to conventional imaging (non-contrast CT and CT angiography) in identifying good treatment candidates among BAO patients is less clear. Patients and methods: This was a multicenter retrospective cohort study of BAO EVT patients treated from 2013 to 2022 in the Stroke Thrombectomy and Aneurysm Registry. Patients selected for EVT by advanced imaging (CTP or MR) were matched with those selected by conventional imaging using propensity score matching (PSM) accounting for possible confounders. Primary outcome was functional independence at 90 days. Other outcomes include bedridden state or death at 90-days and symptomatic intracranial hemorrhage (sICH). Results: 268 patients were included. 150 patients were selected for BAO EVT by conventional imaging, 86 by CTP, and 32 by MR. Patients selected by advanced imaging were significantly older than those selected by conventional imaging (median age 71 vs 64 years, p = 0.001); patient characteristics were otherwise similar between cohorts. After PSM, 90-day outcomes were similar between the two cohorts (p = 0.56), with similar rates of functional independence (39.4% vs 35.1%, p = 0.65), bedridden state or death (40.4% vs 44.7%, p = 0.66), and sICH (3.3% vs 5.7%, p = 0.49) for conventional and advanced imaging groups, respectively. Results were similar across treatment time windows (all p > 0.05). Conclusions: Selecting patients for basilar EVT using conventional versus advanced imaging did not result in different clinical outcomes, regardless of treatment time windows. Conventional imaging appears sufficient as a first-line tool for selecting basilar EVT patients in routine clinical practice.publishersversioninpres
Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of Galen Malformation
No full textThis is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record Normal vascular development includes the formation and specification of arteries, veins, and intervening capillaries. Vein of Galen malformations (VOGMs) are among the most common and severe neonatal brain arterio-venous malformations, shunting arterial blood into the brain's deep venous system through aberrant direct connections. Exome sequencing of 55 VOGM probands, including 52 parent-offspring trios, revealed enrichment of rare damaging de novo mutations in chromatin modifier genes that play essential roles in brain and vascular development. Other VOGM probands harbored rare inherited damaging mutations in Ephrin signaling genes, including a genome-wide significant mutation burden in EPHB4. Inherited mutations showed incomplete penetrance and variable expressivity, with mutation carriers often exhibiting cutaneous vascular abnormalities, suggesting a two-hit mechanism. The identified mutations collectively account for ∼30% of studied VOGM cases. These findings provide insight into disease biology and may have clinical implications for risk assessment.Yale-NIH Center for Mendelian GenomicsNational Institutes of Health (NIH)American Heart AssociationHoward Hughes Institut
