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  1. Book ; Online ; Thesis: Individuelle Strahlenempfindlichkeit in Patienten mit Rektum-Karzinom: Korrelation des durch 3-Farben-FISH-Analyse experimentell bestimmten B/M-Wertes mit strahlentherapie-assoziierten Nebenwirkungen

    Hummel, Christian [Verfasser] / Distel, Luitpold [Akademischer Betreuer] / Distel, Luitpold [Gutachter]

    2022  

    Author's details Christian Hummel ; Gutachter: Luitpold Distel ; Betreuer: Luitpold Distel
    Keywords Medizin, Gesundheit ; Medicine, Health
    Subject code sg610
    Language German
    Publisher Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
    Publishing place Erlangen
    Document type Book ; Online ; Thesis
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  2. Article ; Online: Recurrent ubiquitin B silencing in gynecological cancers establishes dependence on ubiquitin C.

    Kedves, Alexia T / Gleim, Scott / Liang, Xiaoyou / Bonal, Dennis M / Sigoillot, Frederic / Harbinski, Fred / Sanghavi, Sneha / Benander, Christina / George, Elizabeth / Gokhale, Prafulla C / Nguyen, Quang-De / Kirschmeier, Paul T / Distel, Robert J / Jenkins, Jeremy / Goldberg, Michael S / Forrester, William C

    The Journal of clinical investigation

    2017  Volume 127, Issue 12, Page(s) 4554–4568

    Abstract: Transcriptional repression of ubiquitin B (UBB) is a cancer-subtype-specific alteration that occurs ...

    Abstract Transcriptional repression of ubiquitin B (UBB) is a cancer-subtype-specific alteration that occurs in a substantial population of patients with cancers of the female reproductive tract. UBB is 1 of 2 genes encoding for ubiquitin as a polyprotein consisting of multiple copies of ubiquitin monomers. Silencing of UBB reduces cellular UBB levels and results in an exquisite dependence on ubiquitin C (UBC), the second polyubiquitin gene. UBB is repressed in approximately 30% of high-grade serous ovarian cancer (HGSOC) patients and is a recurrent lesion in uterine carcinosarcoma and endometrial carcinoma. We identified ovarian tumor cell lines that retain UBB in a repressed state, used these cell lines to establish orthotopic ovarian tumors, and found that inducible expression of a UBC-targeting shRNA led to tumor regression, and substantial long-term survival benefit. Thus, we describe a recurrent cancer-specific lesion at the level of ubiquitin production. Moreover, these observations reveal the prognostic value of UBB repression and establish UBC as a promising therapeutic target for ovarian cancer patients with recurrent UBB silencing.
    MeSH term(s) Cell Line, Tumor ; Female ; Gene Silencing ; Humans ; Neoplasm Proteins/biosynthesis ; Neoplasm Proteins/genetics ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; Ovarian Neoplasms/therapy ; Ubiquitin/biosynthesis ; Ubiquitin/genetics ; Ubiquitin C/biosynthesis ; Ubiquitin C/genetics
    Chemical Substances Neoplasm Proteins ; UBB protein, human ; Ubiquitin ; Ubiquitin C
    Language English
    Publishing date 2017-11-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI92914
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  3. Article ; Online: B cells in classical Hodgkin lymphoma are important actors rather than bystanders in the local immune reaction.

    Tudor, Christiane S / Distel, Luitpold V / Eckhardt, Jenny / Hartmann, Arndt / Niedobitek, Gerald / Buettner, Maike

    Human pathology

    2013  Volume 44, Issue 11, Page(s) 2475–2486

    Abstract: ... to characterize the potential role of infiltrating B cells and follicular dendritic cell networks in classical ... cytidine deaminase, and CD21 to characterize B cell distribution and follicular structures. To further subclassify ... B cells, analyses of tissue microarrays were performed investigating the expression of Mum1, Bcl6, IgD ...

    Abstract Recent studies, largely focusing on cellular immunity, have demonstrated that the composition of the abundant inflammatory background of Hodgkin lymphoma may affect outcome. This investigation aimed to characterize the potential role of infiltrating B cells and follicular dendritic cell networks in classical Hodgkin lymphoma (cHL) to better assess the role of components of humoral immunity. One hundred two cHL biopsies were investigated by immunohistochemistry with antibodies specific for CD20, CD138, activation-induced cytidine deaminase, and CD21 to characterize B cell distribution and follicular structures. To further subclassify B cells, analyses of tissue microarrays were performed investigating the expression of Mum1, Bcl6, IgD, IgG, IgG4, IgM, T-bet, CD38, CD5, and CD10. For evaluation a computer assisted quantification method was compared with a scoring system. Survival analysis and correlation analysis were performed. The B cell infiltrate was dominated by CD20+ B cells, followed by plasma cells, whereas only few AID+ cells were observed. High numbers of CD21+ follicular dendritic cell networks, CD20+ B cells, IgM+ cells, CD20+ aggregates, and Bcl6+ cells were associated with a better outcome of cHL patients, whereas Pax5+/CD38+ cells had an adverse prognostic impact. Other parameters showed no influence on survival. Our findings suggest that a complex network of B cells is present in the microenvironment of cHL and that B cells might actively contribute to a local anti- as well as pro-tumoral immune response. This indicates that the network of B cells in tumors is probably just as diverse as the T cellular infiltrate and probably functionally as heterogenous.
    MeSH term(s) Adolescent ; Adult ; Antigens, CD20/immunology ; Antigens, CD20/metabolism ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; Dendritic Cells, Follicular/immunology ; Dendritic Cells, Follicular/metabolism ; Epstein-Barr Virus Infections/virology ; Female ; Follow-Up Studies ; Germany ; Germinal Center/immunology ; Germinal Center/metabolism ; Herpesvirus 4, Human/genetics ; Herpesvirus 4, Human/isolation & purification ; Hodgkin Disease/immunology ; Hodgkin Disease/metabolism ; Hodgkin Disease/pathology ; Humans ; Immunity, Humoral ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Plasma Cells/immunology ; Plasma Cells/metabolism ; Prognosis ; Receptors, Complement 3d/immunology ; Receptors, Complement 3d/metabolism ; Syndecan-1/immunology ; Syndecan-1/metabolism ; Tissue Array Analysis ; Young Adult
    Chemical Substances Antigens, CD20 ; Receptors, Complement 3d ; SDC1 protein, human ; Syndecan-1
    Language English
    Publishing date 2013-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 207657-3
    ISSN 1532-8392 ; 0046-8177
    ISSN (online) 1532-8392
    ISSN 0046-8177
    DOI 10.1016/j.humpath.2013.06.006
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  4. Article ; Online: Transport of symbiont-encoded cellulases from the gill to the gut of shipworms via the enigmatic ducts of Deshayes: a 174-year mystery solved.

    Altamia, Marvin A / Distel, Daniel L

    Proceedings. Biological sciences

    2022  Volume 289, Issue 1986, Page(s) 20221478

    Abstract: ... methods to provide evidence for a different mechanism in the shipworm B. setacea ...

    Abstract Shipworms (Bivalvia, Teredinidae) are the principal consumers of wood in marine environments. Like most wood-eating organisms, they digest wood with the aid of cellulolytic enzymes supplied by symbiotic bacteria. However, in shipworms the symbiotic bacteria are not found in the digestive system. Instead, they are located intracellularly in the gland of Deshayes, a specialized tissue found within the gills. It has been independently demonstrated that symbiont-encoded cellulolytic enzymes are present in the digestive systems and gills of two shipworm species, Bankia setacea and Lyrodus pedicellatus, confirming that these enzymes are transported from the gills to the lumen of the gut. However, the mechanism of enzyme transport from gill to gut remains incompletely understood. Recently, a mechanism was proposed by which enzymes are transported within bacterial cells that are expelled from the gill and transported to the mouth by ciliary action of the branchial or food grooves. Here we use in situ immunohistochemical methods to provide evidence for a different mechanism in the shipworm B. setacea, in which cellulolytic enzymes are transported via the ducts of Deshayes, enigmatic structures first described 174 years ago, but whose function have remained unexplained.
    MeSH term(s) Animals ; Gills ; Cellulases ; Phylogeny ; Symbiosis ; Bivalvia/microbiology ; Bacteria
    Chemical Substances Cellulases (EC 3.2.1.-)
    Language English
    Publishing date 2022-11-09
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 209242-6
    ISSN 1471-2954 ; 0080-4649 ; 0962-8452 ; 0950-1193
    ISSN (online) 1471-2954
    ISSN 0080-4649 ; 0962-8452 ; 0950-1193
    DOI 10.1098/rspb.2022.1478
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    Zs.A 1364: Show issues Location:
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  5. Article ; Online: Distribution of immune cells in head and neck cancer: CD8+ T-cells and CD20+ B-cells in metastatic lymph nodes are associated with favourable outcome in patients with oro- and hypopharyngeal carcinoma.

    Pretscher, Dominik / Distel, Luitpold V / Grabenbauer, Gerhard G / Wittlinger, Michael / Buettner, Maike / Niedobitek, Gerald

    BMC cancer

    2009  Volume 9, Page(s) 292

    Abstract: ... infiltrating T-cells. We also show that intratumoural CD20+ B-cells are significantly more frequent ... B-cells in lymph node metastases were associated with favourable outcome. Unexpectedly, no effect ...

    Abstract Background: Tumour infiltrating lymphocytes (TIL) are generally considered to represent a host immune response directed against tumour antigens. TIL are also increasingly recognised as possible prognostic parameters. However, the effects observed are variable indicating that results cannot be extrapolated from type of tumour to another. Moreover, it has been suggested that primary solid tumours may be ignored by the immune system and that a meaningful immune response is only mounted in regional lymph nodes.
    Methods: We have examined the local distribution of immune cells in tumour-related compartments in head and neck squamous cell carcinomas (HNSCC). In a second step, the prognostic impact of these cells on disease-free survival (DFS) was analysed. A total of 198 tissue cores from 33 patients were evaluated using tissue mircroarray technique and immunohistochemistry. Tumour-infiltrating immune cells were identified using antibodies specific for CD3, CD8, GranzymeB, FoxP3, CD20 and CD68 and quantified using an image analysis system.
    Results: We demonstrate a relative expansion of FoxP3+ regulatory T-cells (Treg) and of cytotoxic T-cells among tumour infiltrating T-cells. We also show that intratumoural CD20+ B-cells are significantly more frequent in metastatic deposits than in primary tumours. Furthermore, we observed a reduced number of peritumoural CD8+ T-cells in metastatic lymph nodes as compared to univolved regional nodes suggesting a local down-modulation of cellular immunity. All other immune cells did not show significant alterations in distribution. We did not observe an association of tumour infiltrating immune cells at the primary site with outcome. However, increased numbers of intraepithelial CD8+ TIL in metastatic tumours as well as large numbers of peritumoural B-cells in lymph node metastases were associated with favourable outcome. Unexpectedly, no effect on patient outcome was observed for Treg in any compartment.
    Conclusion: Our results suggest that alterations in lymphocyte distribution in regional lymph nodes rather than at the primary tumour site may be relevant for patient prognosis. Moreover, we demonstrate that in addition to cellular immunity humoral immune responses may be clinically relevant in anti-tumour immunity.
    MeSH term(s) Adult ; Aged ; Antigens, CD20/immunology ; B-Lymphocytes/immunology ; B7-1 Antigen/immunology ; Carcinoma, Squamous Cell/immunology ; Carcinoma, Squamous Cell/pathology ; Female ; Humans ; Lymph Nodes/immunology ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Lymphocyte Subsets/immunology ; Lymphocyte Subsets/pathology ; Lymphocytes, Tumor-Infiltrating/immunology ; Male ; Middle Aged ; Pharyngeal Neoplasms/immunology ; Pharyngeal Neoplasms/pathology
    Chemical Substances Antigens, CD20 ; B7-1 Antigen
    Language English
    Publishing date 2009-08-22
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1471-2407
    ISSN (online) 1471-2407
    DOI 10.1186/1471-2407-9-292
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  6. Article: In Vitro Analysis of Superparamagnetic Iron Oxide Nanoparticles Coated with APTES as Possible Radiosensitizers for HNSCC Cells.

    Emer, Clara / Hildebrand, Laura S / Friedrich, Bernhard / Tietze, Rainer / Fietkau, Rainer / Distel, Luitpold V

    Nanomaterials (Basel, Switzerland)

    2023  Volume 13, Issue 2

    Abstract: Superparamagnetic iron oxide nanoparticles (SPION) are being investigated for many purposes, e.g., for the amplification of ionizing radiation and for the targeted application of therapeutics. Therefore, we investigated SPIONs coated with (3-Aminopropyle) ...

    Abstract Superparamagnetic iron oxide nanoparticles (SPION) are being investigated for many purposes, e.g., for the amplification of ionizing radiation and for the targeted application of therapeutics. Therefore, we investigated SPIONs coated with (3-Aminopropyle)-Triethoxysilane (SPION-APTES) for their influence on different head and neck squamous cell carcinoma (HNSCC) cell lines, as well as for their suitability as a radiosensitizer. We used 24-well microscopy and immunofluorescence microscopy for cell observation, growth curves to determine cytostatic effects, and colony formation assays to determine cytotoxicity. We found that the APTES-SPIONs were very well taken up by the HNSCC cells. They generally have a low cytotoxic effect, showing no significant difference in clonogenic survival between the control group and cells treated with 20 µg Fe/mL (p > 0.25) for all cell lines. They have a cytostatic effect on some cell lines cells (e.g., Cal33) that is visible across different radiation doses (1, 2, 8 Gy, p = 0.05). In Cal33, e.g., SPION-APTES raised the doubling time at 2 Gy from 24.53 h to 41.64 h. Importantly, these findings vary notably between the cell lines. However, they do not significantly alter the radiation effect: only one out of eight cell lines treated with SPION-APTES showed a significantly reduced clonogenic survival after ionizing radiation with 2 Gy, and only two showed significantly reduced doubling times. Thus, although the APTES-SPIONs do not qualify as a radiosensitizer, we were still able to vividly demonstrate and analyze the effect that the APTES-SPIONs have on various cell lines as a contribution to further functionalization.
    Language English
    Publishing date 2023-01-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662255-5
    ISSN 2079-4991
    ISSN 2079-4991
    DOI 10.3390/nano13020330
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  7. Article ; Online: From first report to clinical trials: a bibliometric overview and visualization of the development of Angelman syndrome research.

    Zampeta, F Isabella / Distel, Ben / Elgersma, Ype / Iping, Rik

    Human genetics

    2022  Volume 141, Issue 12, Page(s) 1837–1848

    Abstract: Angelman syndrome is a rare neurodevelopmental disorder caused by mutations affecting the chromosomal 15q11-13 region, either by contiguous gene deletions, imprinting defects, uniparental disomy, or mutations in the UBE3A gene itself. Phenotypic ... ...

    Abstract Angelman syndrome is a rare neurodevelopmental disorder caused by mutations affecting the chromosomal 15q11-13 region, either by contiguous gene deletions, imprinting defects, uniparental disomy, or mutations in the UBE3A gene itself. Phenotypic abnormalities are driven primarily, but not exclusively (especially in 15q11-13 deletion cases) by loss of expression of the maternally inherited UBE3A gene expression. The disorder was first described in 1965 by the English pediatrician Harry Angelman. Since that first description of three children with Angelman syndrome, there has been extensive research into the genetic, molecular and phenotypic aspects of the disorder. In the last decade, this has resulted in over 100 publications per year. Collectively, this research has led the field to a pivotal point in which restoring UBE3A function by genetic therapies is currently explored in several clinical trials. In this study, we employed a bibliometric approach to review and visualize the development of Angelman syndrome research over the last 50 years. We look into different parameters shaping the progress of the Angelman syndrome research field, including source of funding, publishing journals and international collaborations between research groups. Using a network approach, we map the focus of the research field and how that shifted over time. This overview helps understand the shift of research focus in the field and can provide a comprehensive handbook of Angelman syndrome research development.
    MeSH term(s) Child ; Humans ; Angelman Syndrome/genetics ; Angelman Syndrome/therapy ; Ubiquitin-Protein Ligases/genetics ; Mutation ; Bibliometrics ; Chromosomes, Human, Pair 15
    Chemical Substances Ubiquitin-Protein Ligases (EC 2.3.2.27)
    Language English
    Publishing date 2022-05-30
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 223009-4
    ISSN 1432-1203 ; 0340-6717
    ISSN (online) 1432-1203
    ISSN 0340-6717
    DOI 10.1007/s00439-022-02460-x
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 256: Show issues Location:
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  8. Article ; Online: Regulating the human HECT E3 ligases.

    Sluimer, Jasper / Distel, Ben

    Cellular and molecular life sciences : CMLS

    2018  Volume 75, Issue 17, Page(s) 3121–3141

    Abstract: Ubiquitination, the covalent attachment of ubiquitin to proteins, by E3 ligases of the HECT (homologous to E6AP C terminus) family is critical in controlling diverse physiological pathways. Stringent control of HECT E3 ligase activity and substrate ... ...

    Abstract Ubiquitination, the covalent attachment of ubiquitin to proteins, by E3 ligases of the HECT (homologous to E6AP C terminus) family is critical in controlling diverse physiological pathways. Stringent control of HECT E3 ligase activity and substrate specificity is essential for cellular health, whereas deregulation of HECT E3s plays a prominent role in disease. The cell employs a wide variety of regulatory mechanisms to control HECT E3 activity and substrate specificity. Here, we summarize the current understanding of these regulatory mechanisms that control HECT E3 function. Substrate specificity is generally determined by interactions of adaptor proteins with domains in the N-terminal extensions of HECT E3 ligases. These N-terminal domains have also been found to interact with the HECT domain, resulting in the formation of inhibitory conformations. In addition, catalytic activity of the HECT domain is commonly regulated at the level of E2 recruitment and through HECT E3 oligomerization. The previously mentioned regulatory mechanisms can be controlled through protein-protein interactions, post-translational modifications, the binding of calcium ions, and more. Functional activity is determined not only by substrate recruitment and catalytic activity, but also by the type of ubiquitin polymers catalyzed to the substrate. While this is often determined by the specific HECT member, recent studies demonstrate that HECT E3s can be modulated to alter the type of ubiquitin polymers they catalyze. Insight into these diverse regulatory mechanisms that control HECT E3 activity may open up new avenues for therapeutic strategies aimed at inhibition or enhancement of HECT E3 function in disease-related pathways.
    MeSH term(s) Adaptor Proteins, Signal Transducing/metabolism ; Biocatalysis ; Calcium/metabolism ; Humans ; Protein Binding ; Protein Multimerization ; Substrate Specificity ; Ubiquitin-Protein Ligases/chemistry ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination
    Chemical Substances Adaptor Proteins, Signal Transducing ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2018-06-01
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-018-2848-2
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  9. Article ; Online: Increased Radiation Sensitivity in Patients with Phelan-McDermid Syndrome.

    Jesse, Sarah / Kuhlmann, Lukas / Hildebrand, Laura S / Magelssen, Henriette / Schmaus, Martina / Timmermann, Beate / Andres, Stephanie / Fietkau, Rainer / Distel, Luitpold V

    Cells

    2023  Volume 12, Issue 5

    Abstract: Phelan-McDermid syndrome is an inherited global developmental disorder commonly associated with autism spectrum disorder. Due to a significantly increased radiosensitivity, measured before the start of radiotherapy of a rhabdoid tumor in a child with ... ...

    Abstract Phelan-McDermid syndrome is an inherited global developmental disorder commonly associated with autism spectrum disorder. Due to a significantly increased radiosensitivity, measured before the start of radiotherapy of a rhabdoid tumor in a child with Phelan-McDermid syndrome, the question arose whether other patients with this syndrome also have increased radiosensitivity. For this purpose, the radiation sensitivity of blood lymphocytes after irradiation with 2Gray was examined using the G0 three-color fluorescence in situ hybridization assay in a cohort of 20 patients with Phelan-McDermid syndrome from blood samples. The results were compared to healthy volunteers, breast cancer patients and rectal cancer patients. Independent of age and gender, all but two patients with Phelan-McDermid syndrome showed significantly increased radiosensitivity, with an average of 0.653 breaks per metaphase. These results correlated neither with the individual genetic findings nor with the individual clinical course, nor with the respective clinical severity of the disease. In our pilot study, we saw a significantly increased radiosensitivity in lymphocytes from patients with Phelan-McDermid syndrome, so pronounced that a dose reduction would be recommended if radiotherapy had to be performed. Ultimately, the question arises as to the interpretation of these data. There does not appear to be an increased risk of tumors in these patients, since tumors are rare overall. The question, therefore, arose as to whether our results could possibly be the basis for processes, such as aging/preaging, or, in this context, neurodegeneration. There are no data on this so far, but this issue should be pursued in further fundamentally based studies in order to better understand the pathophysiology of the syndrome.
    MeSH term(s) Child ; Humans ; Autism Spectrum Disorder/genetics ; In Situ Hybridization, Fluorescence ; Pilot Projects ; Syndrome ; Neoplasms
    Language English
    Publishing date 2023-03-06
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells12050820
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  10. Article: The Influence of Different Irradiation Regimens on Inflammation and Vascularization in a Random-Pattern Flap Model.

    Müller-Seubert, Wibke / Ostermaier, Patrick / Horch, Raymund E / Distel, Luitpold / Frey, Benjamin / Erber, Ramona / Arkudas, Andreas

    Journal of personalized medicine

    2023  Volume 13, Issue 10

    Abstract: Background: Irradiation plays an important role in the oncological treatment of various tumor entities. The aim of the study was to investigate the influence of different irradiation regimens on random-pattern flaps at the molecular and ... ...

    Abstract Background: Irradiation plays an important role in the oncological treatment of various tumor entities. The aim of the study was to investigate the influence of different irradiation regimens on random-pattern flaps at the molecular and histopathological levels.
    Methods: Twenty-five rats underwent harvesting of bilateral random-pattern fasciocutaneous flaps. The right flaps received irradiation, while the left flaps served as non-irradiated intraindividual controls. Five rats served as a non-irradiated control group. Four different irradiation regimens with give rats each were tested: 20 Gy postoperatively, 3 × 12 Gy postoperatively, 20 Gy preoperatively, and 3 × 12 Gy preoperatively. Two weeks after surgery, HE staining and immunohistochemical staining for CD68 and ERG, as well as PCR analysis to detect Interleukin 6, HIF-1α, and VEGF, were performed.
    Results: A postoperative cumulative higher dose of irradiation appeared to result in an increase in necrosis, especially in the superficial layers of the flap compared to preoperative or single-stage irradiation. In addition, we observed increased expression of VEGF and HIF-1α in all irradiation groups.
    Conclusion: Even though no statistically significant differences were found between the different groups, there was a tendency for fractional postoperative irradiation with a higher total dose to have a more harmful effect compared to preoperative or single-dose irradiation.
    Language English
    Publishing date 2023-10-21
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662248-8
    ISSN 2075-4426
    ISSN 2075-4426
    DOI 10.3390/jpm13101514
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