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  1. Article ; Online: Gastroenteropancreatic Neuroendocrine Tumors.

    Fernandes, Conrad J / Leung, Galen / Eads, Jennifer R / Katona, Bryson W

    Gastroenterology clinics of North America

    2022  Volume 51, Issue 3, Page(s) 625–647

    Abstract: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are the most common type of neuroendocrine tumors and are being increasingly identified in clinical practice. The diagnosis, staging, management, and surveillance of GEP-NETs rely heavily on ... ...

    Abstract Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are the most common type of neuroendocrine tumors and are being increasingly identified in clinical practice. The diagnosis, staging, management, and surveillance of GEP-NETs rely heavily on endoscopy, and consequently, it is important for gastroenterologists to have a solid understanding of these tumors. This article reviews the presentation, diagnosis, and management of both localized and advanced GEP-NETs, with increased emphasis on the role of endoscopy, to enable gastroenterologists and other practitioners to have the necessary tools for the care of patients with these tumors.
    MeSH term(s) Humans ; Intestinal Neoplasms/diagnosis ; Intestinal Neoplasms/epidemiology ; Intestinal Neoplasms/therapy ; Neuroendocrine Tumors/diagnosis ; Neuroendocrine Tumors/therapy ; Pancreatic Neoplasms/diagnosis ; Pancreatic Neoplasms/epidemiology ; Pancreatic Neoplasms/therapy ; Stomach Neoplasms/diagnosis ; Stomach Neoplasms/epidemiology ; Stomach Neoplasms/therapy
    Language English
    Publishing date 2022-08-30
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 92114-2
    ISSN 1558-1942 ; 0889-8553
    ISSN (online) 1558-1942
    ISSN 0889-8553
    DOI 10.1016/j.gtc.2022.06.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Intraoperative Pulmonary Embolism in an Adolescent Patient with Type III Spinal Muscular Atrophy: A Case Report.

    Fernandes, Carlton J / Fernandes, Conrad J / Chong, David Y

    JBJS case connector

    2020  Volume 10, Issue 3, Page(s) e20.00087

    Abstract: Case: We present the case of an 11-year-old girl with spinal muscular atrophy (SMA) type III who suffered an intraoperative venous thromboembolism (VTE), leading to death during bilateral extremity contracture releases for deformity correction.: ... ...

    Abstract Case: We present the case of an 11-year-old girl with spinal muscular atrophy (SMA) type III who suffered an intraoperative venous thromboembolism (VTE), leading to death during bilateral extremity contracture releases for deformity correction.
    Conclusion: Given the increasing incidence of VTE in pediatric patients, further consideration should be given to broadening the patient population offerring preoperative deep vein thrombosis screening or thromboprophylaxis. Specifically, patients with previous trauma, neuromuscular disorders, and prolonged immobilization or contractures should receive special attention. In addition, SMA may cause hypercoagulability independent of its status as a neuromuscular disorder, and this link should be investigated further.
    MeSH term(s) Child ; Extracorporeal Membrane Oxygenation/adverse effects ; Fatal Outcome ; Female ; Humans ; Hypoxia-Ischemia, Brain/etiology ; Hypoxia-Ischemia, Brain/therapy ; Intraoperative Complications/etiology ; Pulmonary Embolism/complications ; Spinal Muscular Atrophies of Childhood/complications ; Spinal Muscular Atrophies of Childhood/surgery
    Language English
    Publishing date 2020-05-06
    Publishing country United States
    Document type Case Reports ; Journal Article
    ISSN 2160-3251
    ISSN (online) 2160-3251
    DOI 10.2106/JBJS.CC.20.00087
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Rates of Intervention and Cancer Detection on Initial versus Subsequent Whole-body MRI Screening in Li-Fraumeni Syndrome.

    Kagami, Laura A T / Du, Yun K / Fernandes, Conrad J / Le, Anh N / Good, Madeline / Duvall, Melani M / Baldino, Sarah E / Powers, Jacquelyn / Zelley, Kristin / States, Lisa J / Mathew, Manoj C / Katona, Bryson W / MacFarland, Suzanne P / Maxwell, Kara N

    Cancer prevention research (Philadelphia, Pa.)

    2023  Volume 16, Issue 9, Page(s) 507–512

    Abstract: Li-Fraumeni Syndrome (LFS) is a hereditary cancer predisposition syndrome with up to 90% lifetime cancer risk. Cancer screening, including annual whole-body MRI (WB-MRI), is recommended due to known survival advantage, with cancer detection rate of 7% on ...

    Abstract Li-Fraumeni Syndrome (LFS) is a hereditary cancer predisposition syndrome with up to 90% lifetime cancer risk. Cancer screening, including annual whole-body MRI (WB-MRI), is recommended due to known survival advantage, with cancer detection rate of 7% on initial screening. Intervention and cancer detection rates on subsequent screenings are unknown. Clinical data for pediatric and adult patients with LFS (n = 182) were reviewed, including instances of WB-MRI screening and interventions based on screening results. For each WB-MRI screening, interventions including biopsy and secondary imaging, as well as rate of cancer diagnosis, were analyzed comparing initial versus subsequent WB-MRI. Of the total cohort (n = 182), we identified 68 adult patients and 50 pediatric patients who had undergone at least two WB-MRI screenings, with a mean of 3.8 ± 1.9 (adults) and 4.0 ± 2.1 (pediatric) screenings. Findings on initial screening led to an imaging or invasive intervention in 38% of adults and 20% of children. On follow up, overall intervention rates were lower for adults (19%, P = 0.0026) and stable for children (19%, P = NS). Thirteen cancers were detected overall (7% of adult and 14% of pediatric scans), on both initial (pediatric: 4%, adult: 3%) and subsequent (pediatric: 10%, adult: 6%) screenings. Rates of intervention after WB-MRI screening decreased significantly in adults between first and subsequent exams and remained stable in pediatric patients. Cancer detection rates were similar on screening (3%-4% initial, 6%-10% subsequent) for both children and adults. These findings provide important data for counseling patients with LFS about screening outcomes.
    Prevention relevance: The cancer detection rate, burden of recommended interventions, and rate of false-positive findings found on subsequent WB-MRI screenings in patients with LFS are not well understood. Our findings suggest that annual WB-MRI screening has clinical utility and likely does not result in an unnecessary invasive intervention burden for patients.
    MeSH term(s) Adult ; Humans ; Child ; Li-Fraumeni Syndrome/diagnostic imaging ; Li-Fraumeni Syndrome/genetics ; Early Detection of Cancer/methods ; Whole Body Imaging/methods ; Magnetic Resonance Imaging ; Genotype ; Genetic Predisposition to Disease
    Language English
    Publishing date 2023-07-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2434717-6
    ISSN 1940-6215 ; 1940-6207
    ISSN (online) 1940-6215
    ISSN 1940-6207
    DOI 10.1158/1940-6207.CAPR-23-0011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6766: Show issues Location:
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  4. Article ; Online: Mitochondrial fusion exploits a therapeutic vulnerability of pancreatic cancer.

    Yu, Meifang / Nguyen, Nicholas D / Huang, Yanqing / Lin, Daniel / Fujimoto, Tara N / Molkentine, Jessica M / Deorukhkar, Amit / Kang, Ya'an / San Lucas, F Anthony / Fernandes, Conrad J / Koay, Eugene J / Gupta, Sonal / Ying, Haoqiang / Koong, Albert C / Herman, Joseph M / Fleming, Jason B / Maitra, Anirban / Taniguchi, Cullen M

    JCI insight

    2019  Volume 5

    Abstract: Pancreatic ductal adenocarcinoma (PDAC) requires mitochondrial oxidative phosphorylation (OXPHOS) to fuel its growth, however, broadly inhibiting this pathway might also disrupt essential mitochondrial functions in normal tissues. PDAC cells exhibit ... ...

    Abstract Pancreatic ductal adenocarcinoma (PDAC) requires mitochondrial oxidative phosphorylation (OXPHOS) to fuel its growth, however, broadly inhibiting this pathway might also disrupt essential mitochondrial functions in normal tissues. PDAC cells exhibit abnormally fragmented mitochondria that are essential to its oncogenicity, but it was unclear if this mitochondrial feature was a valid therapeutic target. Here, we present evidence that normalizing the fragmented mitochondria of pancreatic cancer via the process of mitochondrial fusion reduces OXPHOS, which correlates with suppressed tumor growth and improved survival in preclinical models. Mitochondrial fusion was achieved by genetic or pharmacologic inhibition of dynamin related protein-1 (Drp1) or through overexpression of mitofusin-2 (Mfn2). Notably, we found that oral leflunomide, an FDA-approved arthritis drug, promoted a two-fold increase in Mfn2 expression in tumors and was repurposed as a chemotherapeutic agent, improving the median survival of mice with spontaneous tumors by 50% compared to vehicle. We found that the chief tumor suppressive mechanism of mitochondrial fusion was enhanced mitophagy, which proportionally reduced mitochondrial mass and ATP production. These data suggest that mitochondrial fusion is a specific and druggable regulator of pancreatic cancer growth that could be rapidly translated to the clinic.
    MeSH term(s) Animals ; CRISPR-Cas Systems ; Carcinoma, Pancreatic Ductal/metabolism ; Disease Models, Animal ; Dynamins/antagonists & inhibitors ; Dynamins/genetics ; Enzyme Inhibitors/pharmacology ; GTP Phosphohydrolases/genetics ; Leflunomide/pharmacology ; Mice ; Mice, Knockout ; Mitochondria/metabolism ; Mitochondrial Dynamics/drug effects ; Mitochondrial Dynamics/genetics ; Mitophagy/drug effects ; Mitophagy/genetics ; Oxidative Phosphorylation/drug effects ; Pancreatic Neoplasms/metabolism ; Quinazolinones/pharmacology ; Survival Rate
    Chemical Substances 3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone ; Enzyme Inhibitors ; Quinazolinones ; GTP Phosphohydrolases (EC 3.6.1.-) ; Mfn2 protein, mouse (EC 3.6.1.-) ; Dnm1l protein, mouse (EC 3.6.5.5) ; Dynamins (EC 3.6.5.5) ; Leflunomide (G162GK9U4W)
    Language English
    Publishing date 2019-07-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Video-Audio Media
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.126915
    Database MEDical Literature Analysis and Retrieval System OnLINE

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