LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 30

Search options

  1. Article ; Online: Implementierung einer neuen Versorgungsform zur Früherkennung und Prävention emotionaler und Verhaltensauffälligkeiten bei Kindern im kinderärztlichen Setting: Qualitative Interviews mit Kinderärzt*innen, Praxispersonal und Sorgeberechtigten.

    Hense, Helene / Ernst, Sophia / Zscheppang, Anja / Schmitt, Jochen / Roessner, Veit / Weniger, Max / Beesdo-Baum, Katja / Knappe, Susanne

    Zeitschrift fur Evidenz, Fortbildung und Qualitat im Gesundheitswesen

    2024  Volume 185, Page(s) 92–107

    Abstract: Aim of the study: Evaluation of the implementation of a standardized screening using the Strengths and Difficulties Questionnaire (SDQ) as part of the routine pediatric health check-ups in the Dresden area (Germany) in order to detect emotional and ... ...

    Title translation Implementation of a novel form of care for the early detection and prevention of emotional and behavioral problems in children in the pediatric setting: Qualitative interviews with pediatricians, practice staff and parents.
    Abstract Aim of the study: Evaluation of the implementation of a standardized screening using the Strengths and Difficulties Questionnaire (SDQ) as part of the routine pediatric health check-ups in the Dresden area (Germany) in order to detect emotional and behavioral problems (EBPs) in children early and allocate them to indicated preventive programs and/or to further counselling and treatment services.
    Methods: 1.) Semi-structured interviews were performed with participating pediatricians (n=4), practice staff (n=4) and custodians of screened children (n=17) and subjected to content analysis regarding feasibility, advantages and disadvantages of the screening and the targeted allocation, as well as barriers and facilitators of using the screening and the preventive programs and further services. 2.) A self-developed questionnaire survey (descriptive analysis: means and frequencies) was conducted among pediatricians (n=34/99) to inquire about the implementation of the SDQ screening regarding feasibility, advantages, disadvantages and necessary conditions for a potential adoption of the screening to standard health services.
    Results: In the interviews, the pediatricians and practice staff reported that the SDQ screening embedded in routine pediatric health check-ups was simple and could be carried out in a few minutes. The screening helped to identify and address possible EBPs in children and to recommend a targeted service. Apart from the expenditure of time, no disadvantages were mentioned. As expected, parent-related (e.g. fears, attitudes and trust in the pediatrician), child-related (does not want to reveal any information about him- or herself , attitude and motivation), service provider-related (presentation of services), organizational (necessary signatures, financing, waiting time) and service-related (duration, costs, venue, designation) factors influenced the families' use of the screening and further services. Interviewed custodians whose child participated in an indicated preventive program within the project (n=11) would recommend the SDQ screening and preventive program to other families. In the questionnaire survey 28/31 pediatricians "completely" or "rather" agreed on a 5-point Likert scale that the SDQ screening and targeted allocation should be included in standard pediatric care.
    Discussion: The use of the SDQ, which is one of the most widely used and, despite its brevity, most valid screening instruments for the early detection of EBPs, in routine pediatric health check-ups and the targeted allocation of further health services represent a feasible approach to the early identification and clarification of EBPs in children as well as their allocation to indicated preventive services.
    Conclusion: An adoption of the novel form of care (SDQ screening and targeted allocation to indicated preventive programs and further services) to standard pediatric care unfolds its benefits if preventive and care services for EBPs in children are made available nationwide.
    MeSH term(s) Humans ; Male ; Problem Behavior ; Germany ; Parents/psychology ; Family ; Surveys and Questionnaires
    Language German
    Publishing date 2024-03-19
    Publishing country Netherlands
    Document type English Abstract ; Journal Article
    ZDB-ID 2412512-X
    ISSN 2212-0289 ; 1865-9217
    ISSN (online) 2212-0289
    ISSN 1865-9217
    DOI 10.1016/j.zefq.2023.12.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: Bone marrow stem cells accelerate lung maturation and prevent the LPS-induced delay of morphological and functional fetal lung development in the presence of ErbB4.

    Schmiedl, Andreas / Bokel, Kyra / Huhn, Verena / Ionescu, Lavinia / Zscheppang, Katja / Dammann, Christiane E L

    Cell and tissue research

    2020  Volume 380, Issue 3, Page(s) 547–564

    Abstract: ErbB4 is a regulator in lung development and disease. Prenatal infection is an important risk factor for the delay of morphologic lung development, while promoting the maturation of the surfactant system. Bone marrow-derived mesenchymal stem cells (BMSCs) ...

    Abstract ErbB4 is a regulator in lung development and disease. Prenatal infection is an important risk factor for the delay of morphologic lung development, while promoting the maturation of the surfactant system. Bone marrow-derived mesenchymal stem cells (BMSCs) have the potential to prevent lung injury. We hypothesized that BMSCs in comparison with hematopoietic control stem cells (HPSCs) minimize the lipopolysaccharide (LPS)-induced lung injury only when functional ErbB4 receptor is present. We injected LPS and/or murine green fluorescent protein-labeled BMSCs or HPSCs into the amniotic cavity of transgenic ErbB4
    MeSH term(s) Animals ; Female ; Fetal Development ; Fetus ; Lipopolysaccharides ; Lung/embryology ; Lung/pathology ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/cytology ; Mice ; Mice, Transgenic ; Organogenesis ; Receptor, ErbB-4/physiology
    Chemical Substances Lipopolysaccharides ; Erbb4 protein, mouse (EC 2.7.10.1) ; Receptor, ErbB-4 (EC 2.7.10.1)
    Language English
    Publishing date 2020-02-13
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 125067-x
    ISSN 1432-0878 ; 0302-766X
    ISSN (online) 1432-0878
    ISSN 0302-766X
    DOI 10.1007/s00441-019-03145-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article: Efficacy of Beta1 Integrin and EGFR Targeting in Sphere-Forming Human Head and Neck Cancer Cells.

    Zscheppang, Katja / Kurth, Ina / Wachtel, Nicole / Dubrovska, Anna / Kunz-Schughart, Leoni A / Cordes, Nils

    Journal of Cancer

    2016  Volume 7, Issue 6, Page(s) 736–745

    Abstract: Background: Resistance to radiotherapy continues to be a limiting factor in the treatment of cancer including head and neck squamous cell carcinoma (HNSCC). Simultaneous targeting of β1 integrin and EGFR was shown to have a higher radiosensitizing ... ...

    Abstract Background: Resistance to radiotherapy continues to be a limiting factor in the treatment of cancer including head and neck squamous cell carcinoma (HNSCC). Simultaneous targeting of β1 integrin and EGFR was shown to have a higher radiosensitizing potential than mono-targeting in the majority of tested HNSCC cancer models. As tumor-initiating cells (TIC) are thought to play a key role for therapy resistance and recurrence and can be enriched in sphere forming conditions, this study investigated the efficacy of β1 integrin/EGFR targeting without and in combination with X-ray irradiation on the behavior of sphere-forming cells (SFC).
    Methods: HNSCC cell lines (UTSCC15, UTSCC5, Cal33, SAS) were injected subcutaneously into nude mice for tumor up-take and plated for primary and secondary sphere formation under non-adhesive conditions which is thought to reflect the enrichment of SFC and their self-renewal capacity, respectively. Treatment was accomplished by inhibitory antibodies for β1 integrin (AIIB2) and EGFR (Cetuximab) as well as X-ray irradiation (2 - 6 Gy single doses). Further, flow cytometry for TIC marker expression and cell cycling as well as Western blotting for DNA repair protein expression and phosphorylation were employed.
    Results: We found higher primary and secondary sphere forming capacity of SAS cells relative to other HNSCC cell lines, which was in line with the tumor up-take rates of SAS versus UTSCC15 cells. AIIB2 and Cetuximab administration had minor cytotoxic and no radiosensitizing effects on SFC. Intriguingly, secondary SAS spheres, representing the fraction of surviving SFC upon passaging, showed greatly enhanced radiosensitivity compared to primary spheres. Intriguingly, neither AIIB2 nor Cetuximab significantly altered basal sphere forming capacity and radiosensitivity. While an increased accumulation of G0/G1 phase cells was observable in secondary SAS spheres, DNA double strand break repair indicated no difference on the basis of significantly enhanced ATM and Chk2 dephosphorylation upon irradiation.
    Conclusions: In the HNSCC model, sphere-forming conditions select for cells, which are unsusceptible to both anti-β1 integrin and anti-EGFR inhibitory antibodies. With regard to primary and secondary sphere formation, our data suggest that both of these SFC fractions express distinct survival strategies independent from β1 integrin and EGFR and that future work is warranted to better understand SFC survival and enrichment before and after treatment to untangle the underlying mechanisms for identifying novel, druggable cancer targets in SFC.
    Language English
    Publishing date 2016-04-02
    Publishing country Australia
    Document type Journal Article
    ZDB-ID 2573318-7
    ISSN 1837-9664
    ISSN 1837-9664
    DOI 10.7150/jca.14232
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Article ; Online: Human Pulmonary 3D Models For Translational Research.

    Zscheppang, Katja / Berg, Johanna / Hedtrich, Sarah / Verheyen, Leonie / Wagner, Darcy E / Suttorp, Norbert / Hippenstiel, Stefan / Hocke, Andreas C

    Biotechnology journal

    2017  Volume 13, Issue 1

    Abstract: Lung diseases belong to the major causes of death worldwide. Recent innovative methodological developments now allow more and more for the use of primary human tissue and cells to model such diseases. In this regard, the review covers bronchial air- ... ...

    Abstract Lung diseases belong to the major causes of death worldwide. Recent innovative methodological developments now allow more and more for the use of primary human tissue and cells to model such diseases. In this regard, the review covers bronchial air-liquid interface cultures, precision cut lung slices as well as ex vivo cultures of explanted peripheral lung tissue and de-/re-cellularization models. Diseases such as asthma or infections are discussed and an outlook on further areas for development is given. Overall, the progress in ex vivo modeling by using primary human material could make translational research activities more efficient by simultaneously fostering the mechanistic understanding of human lung diseases while reducing animal usage in biomedical research.
    MeSH term(s) Bronchi/cytology ; Epithelial Cells/cytology ; Humans ; Lung Diseases/physiopathology ; Lung Diseases/therapy ; Translational Research, Biomedical
    Keywords covid19
    Language English
    Publishing date 2017-09-20
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 2221885-3
    ISSN 1860-7314 ; 1860-6768
    ISSN (online) 1860-7314
    ISSN 1860-6768
    DOI 10.1002/biot.201700341
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article: ErbB4 is an upstream regulator of TTF-1 fetal mouse lung type II cell development in vitro

    Zscheppang, Katja / Giese, Ulrike / Hoenzke, Stefan / Wiegel, Dorothea / Dammann, Christiane E.L

    Biochimica et biophysica acta. Molecular cell research. 2013 Dec., v. 1833, no. 12

    2013  

    Abstract: TTF-1 is an important transcription factor in lung development and lung disease and is essential for lung cell differentiation, specifically surfactant protein (Sftp) expression. The molecular mechanisms that drive the expression and transcriptional ... ...

    Abstract TTF-1 is an important transcription factor in lung development and lung disease and is essential for lung cell differentiation, specifically surfactant protein (Sftp) expression. The molecular mechanisms that drive the expression and transcriptional control of TTF-1 are not fully understood. In the fetal lung, ErbB4 functions as a transcriptional co-factor and regulates the timely onset of fetal Sftp expression. We speculate that ErbB4 is an upstream regulator of TTF-1 and regulates Sftpb expression via this pathway in alveolar type II cells. Neuregulin-induced ErbB4 and TTF-1 signaling interactions were studied by co-immunoprecipitation and confocal microscopy. Overexpression of ErbB4 and TTF-1 was analyzed in its effect on cell viability, Sftpb expression, TTF-1 expression, and Sftpb and TTF-1 promoter activity. The effect of ErbB4 deletion and ErbB4 nuclear translocation on TTF-1 expression was studied in primary fetal type II epithelial cells, isolated from transgenic HER4heart(−/−) mice. ErbB4 ligand neuregulin induces ErbB4 and TTF-1 co-precipitation and nuclear colocalization. Combined ErbB4 and TTF-1 overexpression inhibits cell viability, while promoting Sftpb expression more than single overexpression of each protein. NRG stimulates TTF-1 expression in ErbB4-overexpressing epithelial cells, while this effect is absent in ErbB4-depleted cells. In primary fetal type II cells, ErbB4 nuclear translocation is critical for its regulation of TTF-1-induced Sftpb upregulation. TTF-1 overexpression did not overcome this important requirement. We conclude that ErbB4 is a critical upstream regulator of TTF-1 in type II epithelial cells and that this interaction is important for Sftpb regulation.
    Keywords cell differentiation ; cell viability ; confocal microscopy ; coprecipitation ; epithelial cells ; genetically modified organisms ; mice ; surfactants ; transcription (genetics) ; transcription factors
    Language English
    Dates of publication 2013-12
    Size p. 2690-2702.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 283444-3
    ISSN 0167-4889
    ISSN 0167-4889
    DOI 10.1016/j.bbamcr.2013.06.030
    Database NAL-Catalogue (AGRICOLA)

    More links

    Kategorien

  6. Article ; Online: A novel European H5N8 influenza A virus has increased virulence in ducks but low zoonotic potential.

    Grund, Christian / Hoffmann, Donata / Ulrich, Reiner / Naguib, Mahmoud / Schinköthe, Jan / Hoffmann, Bernd / Harder, Timm / Saenger, Sandra / Zscheppang, Katja / Tönnies, Mario / Hippenstiel, Stefan / Hocke, Andreas / Wolff, Thorsten / Beer, Martin

    Emerging microbes & infections

    2018  Volume 7, Issue 1, Page(s) 132

    Abstract: We investigated in a unique setup of animal models and a human lung explant culture biological properties, including zoonotic potential, of a representative 2016 highly pathogenic avian influenza virus (HPAIV) H5N8, clade 2.3.4.4 group B (H5N8B), that ... ...

    Abstract We investigated in a unique setup of animal models and a human lung explant culture biological properties, including zoonotic potential, of a representative 2016 highly pathogenic avian influenza virus (HPAIV) H5N8, clade 2.3.4.4 group B (H5N8B), that spread rapidly in a huge and ongoing outbreak series in Europe and caused high mortality in waterfowl and domestic birds. HPAIV H5N8B showed increased virulence with rapid onset of severe disease and mortality in Pekin ducks due to pronounced neuro- and hepatotropism. Cross-species infection was evaluated in mice, ferrets, and in a human lung explant culture model. While the H5N8B isolate was highly virulent for Balb/c mice, virulence and transmissibility were grossly reduced in ferrets, which was mirrored by marginal replication in human lung cultures infected ex vivo. Our data indicate that the 2016 HPAIV H5N8B is avian-adapted with augmented virulence for waterfowl, but has low zoonotic potential. The here tested combination of animal studies with the inoculation of human explants provides a promising future workflow to evaluate zoonotic potential, mammalian replication competence and avian virulence of HPAIV.
    MeSH term(s) Animals ; Disease Outbreaks/veterinary ; Ducks/virology ; Ferrets/virology ; Humans ; Influenza A Virus, H5N8 Subtype/pathogenicity ; Influenza in Birds/transmission ; Influenza in Birds/virology ; Influenza, Human/transmission ; Influenza, Human/virology ; Lung/pathology ; Lung/virology ; Mice, Inbred BALB C ; Poultry Diseases/transmission ; Poultry Diseases/virology ; Virulence ; Virus Replication ; Zoonoses/transmission ; Zoonoses/virology
    Keywords covid19
    Language English
    Publishing date 2018-07-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2681359-2
    ISSN 2222-1751 ; 2222-1751
    ISSN (online) 2222-1751
    ISSN 2222-1751
    DOI 10.1038/s41426-018-0130-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  7. Article: ErbB4 is an upstream regulator of TTF-1 fetal mouse lung type II cell development in vitro.

    Zscheppang, Katja / Giese, Ulrike / Hoenzke, Stefan / Wiegel, Dorothea / Dammann, Christiane E L

    Biochimica et biophysica acta

    2013  Volume 1833, Issue 12, Page(s) 2690–2702

    Abstract: TTF-1 is an important transcription factor in lung development and lung disease and is essential for lung cell differentiation, specifically surfactant protein (Sftp) expression. The molecular mechanisms that drive the expression and transcriptional ... ...

    Abstract TTF-1 is an important transcription factor in lung development and lung disease and is essential for lung cell differentiation, specifically surfactant protein (Sftp) expression. The molecular mechanisms that drive the expression and transcriptional control of TTF-1 are not fully understood. In the fetal lung, ErbB4 functions as a transcriptional co-factor and regulates the timely onset of fetal Sftp expression. We speculate that ErbB4 is an upstream regulator of TTF-1 and regulates Sftpb expression via this pathway in alveolar type II cells. Neuregulin-induced ErbB4 and TTF-1 signaling interactions were studied by co-immunoprecipitation and confocal microscopy. Overexpression of ErbB4 and TTF-1 was analyzed in its effect on cell viability, Sftpb expression, TTF-1 expression, and Sftpb and TTF-1 promoter activity. The effect of ErbB4 deletion and ErbB4 nuclear translocation on TTF-1 expression was studied in primary fetal type II epithelial cells, isolated from transgenic HER4(heart(-/-)) mice. ErbB4 ligand neuregulin induces ErbB4 and TTF-1 co-precipitation and nuclear colocalization. Combined ErbB4 and TTF-1 overexpression inhibits cell viability, while promoting Sftpb expression more than single overexpression of each protein. NRG stimulates TTF-1 expression in ErbB4-overexpressing epithelial cells, while this effect is absent in ErbB4-depleted cells. In primary fetal type II cells, ErbB4 nuclear translocation is critical for its regulation of TTF-1-induced Sftpb upregulation. TTF-1 overexpression did not overcome this important requirement. We conclude that ErbB4 is a critical upstream regulator of TTF-1 in type II epithelial cells and that this interaction is important for Sftpb regulation.
    MeSH term(s) Alveolar Epithelial Cells/cytology ; Alveolar Epithelial Cells/drug effects ; Alveolar Epithelial Cells/metabolism ; Animals ; Cell Line ; Cell Nucleus/drug effects ; Cell Nucleus/metabolism ; Cell Survival/drug effects ; Cell Survival/genetics ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; ErbB Receptors/chemistry ; ErbB Receptors/metabolism ; Fetus/cytology ; Fetus/drug effects ; Fetus/metabolism ; Gene Expression Regulation, Developmental/drug effects ; Humans ; Immunoprecipitation ; Mice ; Models, Biological ; Neuregulins/pharmacology ; Promoter Regions, Genetic/genetics ; Protein Structure, Tertiary ; Protein Transport/drug effects ; Pulmonary Surfactant-Associated Protein B/genetics ; Pulmonary Surfactant-Associated Protein B/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Receptor, ErbB-4 ; Transcription Factors
    Chemical Substances DNA-Binding Proteins ; Neuregulins ; Pulmonary Surfactant-Associated Protein B ; RNA, Messenger ; Transcription Factors ; Ttf1 protein, mouse ; ERBB4 protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1) ; Erbb4 protein, mouse (EC 2.7.10.1) ; Receptor, ErbB-4 (EC 2.7.10.1)
    Language English
    Publishing date 2013-07-08
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 60-7
    ISSN 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbamcr.2013.06.030
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  8. Article ; Online: Simultaneous β1 integrin-EGFR targeting and radiosensitization of human head and neck cancer.

    Eke, Iris / Zscheppang, Katja / Dickreuter, Ellen / Hickmann, Linda / Mazzeo, Ercole / Unger, Kristian / Krause, Mechthild / Cordes, Nils

    Journal of the National Cancer Institute

    2015  Volume 107, Issue 2

    Abstract: Background: Signaling from integrins and receptor tyrosine kinases (RTKs) contributes substantially to therapy resistance of malignant tumors. We investigated simultaneous β1 integrin-epidermal growth factor receptor (EGFR) targeting plus radiotherapy ... ...

    Abstract Background: Signaling from integrins and receptor tyrosine kinases (RTKs) contributes substantially to therapy resistance of malignant tumors. We investigated simultaneous β1 integrin-epidermal growth factor receptor (EGFR) targeting plus radiotherapy in human head and neck squamous cell carcinomas (HNSCCs).
    Methods: Ten HNSCC cell lines were grown in three-dimensional laminin-rich extracellular matrix cell cultures and two of them as tumor xenografts in nude mice (n = 12-16 per group). Targeting of β1 integrin and EGFR with monoclonal inhibitory antibodies (AIIB2 and cetuximab, respectively) was combined with x-ray irradiation. Clonogenic survival, tumor growth, and tumor control (evaluated by Kaplan-Meier analysis), apoptosis, phosphoproteome (interactome, network betweeness centrality analysis), receptor expression (immunohistochemistry), and downstream signaling (western blotting) were assessed. Various mutants of the integrin signaling mediator focal adhesion kinase (FAK) were employed for mechanistic studies. All statistical tests were two-sided.
    Results: Compared with β1 integrin or EGFR single inhibition, combined β1 integrin-EGFR targeting resulted in enhanced cytotoxicity and radiosensitization in eight out of 10 tested HNSCC cell lines, which responded with an FAK dephosphorylation after β1 integrin inhibition. In vivo, simultaneous anti-β1 integrin/anti-EGFR treatment and radiotherapy of UTSCC15 responder xenografts enabled better tumor control compared with anti-EGFR monotherapy and irradiation (hazard ratio [HR] = 6.9, 95% confidence interval [CI] = 1.6 to 30.9, P = .01), in contrast to the SAS nonresponder tumor model (HR = 0.9, 95% CI = 0.4 to 2.3, P = .83). Mechanistically, a protein complex consisting of FAK- and Erk1-mediated prosurvival signals for radiation resistance, which was effectively compromised by β1 integrin and EGFR blocking.
    Conclusions: Concomitant targeting of β1 integrin and EGFR seems a powerful and promising approach to overcome radioresistance of HNSCCs.
    MeSH term(s) Animals ; Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antibodies, Monoclonal, Humanized/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Apoptosis ; Blotting, Western ; Carcinoma, Squamous Cell/drug therapy ; Carcinoma, Squamous Cell/radiotherapy ; Carcinoma, Squamous Cell/therapy ; Cell Line, Tumor ; Cetuximab ; ErbB Receptors/antagonists & inhibitors ; Focal Adhesion Kinase 1/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Head and Neck Neoplasms/drug therapy ; Head and Neck Neoplasms/radiotherapy ; Head and Neck Neoplasms/therapy ; Humans ; Immunohistochemistry ; Integrin beta1/drug effects ; Kaplan-Meier Estimate ; Mice ; Mice, Nude ; Mitogen-Activated Protein Kinase 3/metabolism ; Molecular Targeted Therapy/methods ; Odds Ratio ; Radiation-Sensitizing Agents/therapeutic use ; Signal Transduction ; Squamous Cell Carcinoma of Head and Neck ; Xenograft Model Antitumor Assays
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Integrin beta1 ; Radiation-Sensitizing Agents ; EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1) ; Focal Adhesion Kinase 1 (EC 2.7.10.2) ; PTK2 protein, human (EC 2.7.10.2) ; Mitogen-Activated Protein Kinase 3 (EC 2.7.11.24) ; Cetuximab (PQX0D8J21J)
    Language English
    Publishing date 2015-02-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2992-0
    ISSN 1460-2105 ; 0027-8874 ; 0198-0157
    ISSN (online) 1460-2105
    ISSN 0027-8874 ; 0198-0157
    DOI 10.1093/jnci/dju419
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  9. Article ; Online: EGFR and β1-integrin targeting differentially affect colorectal carcinoma cell radiosensitivity and invasion.

    Poschau, Mandy / Dickreuter, Ellen / Singh-Müller, Jenny / Zscheppang, Katja / Eke, Iris / Liersch, Torsten / Cordes, Nils

    Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

    2015  Volume 116, Issue 3, Page(s) 510–516

    Abstract: Background and purpose: Simultaneous targeting of β1 integrin receptor and epidermal growth factor receptor (EGFR) showed higher level of radiosensitization in head and neck cancers than monotherapies. As EGFR inhibition is similarly performed in ... ...

    Abstract Background and purpose: Simultaneous targeting of β1 integrin receptor and epidermal growth factor receptor (EGFR) showed higher level of radiosensitization in head and neck cancers than monotherapies. As EGFR inhibition is similarly performed in colorectal cancer (CRC), we investigated the radiosensitizing and anti-invasive potential of β1-integrin/EGFR inhibition in CRC cell lines grown in more physiological three-dimensional (3D) matrix-based cell cultures.
    Materials and methods: DLD-1 and HT-29 cells were used for 3D-colony formation, invasion and proliferation assays and Western blotting. β1 integrin, focal adhesion kinase and EGFR were inhibited by AIIB2, TAE226 and Cetuximab, respectively. KRAS and BRAF knockdown were accomplished using small-interfering RNA technology. Single doses of X-rays ranged from 2Gy to 6Gy and 5-fluorouracil (5-FU) concentration was 10μM.
    Results: Neither β1-integrin/EGFR inhibition nor KRAS or BRAF depletion nor 5-FU significantly modified CRC cell radiosensitivity. Cetuximab, AIIB2 and Cetuximab/AIIB2 differentially modulated MAPK, JNK and AKT phosphorylation. AIIB2 and TAE226 significantly decreased cell invasion.
    Conclusions: Our data show inefficiency of Cetuximab and AIIB2 on top of radiochemotherapy. The functions of KRAS and BRAF in therapy resistance remain unanswered and warrant further preclinical molecular-driven investigations. One promising approach might be β1 integrin targeting for reducing metastatic CRC cell spread.
    MeSH term(s) Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cetuximab/pharmacology ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/radiotherapy ; Fluorouracil/pharmacology ; Focal Adhesion Kinase 1/metabolism ; Focal Adhesion Protein-Tyrosine Kinases/metabolism ; HT29 Cells ; Humans ; Integrin beta1/metabolism ; Neoplasm Invasiveness ; RNA, Small Interfering/pharmacology ; Radiation Tolerance/drug effects ; Radiation-Sensitizing Agents/pharmacology ; Receptor, Epidermal Growth Factor/antagonists & inhibitors
    Chemical Substances Antineoplastic Agents ; Integrin beta1 ; RNA, Small Interfering ; Radiation-Sensitizing Agents ; Receptor, Epidermal Growth Factor (EC 2.7.10.1) ; Focal Adhesion Kinase 1 (EC 2.7.10.2) ; Focal Adhesion Protein-Tyrosine Kinases (EC 2.7.10.2) ; PTK2 protein, human (EC 2.7.10.2) ; Cetuximab (PQX0D8J21J) ; Fluorouracil (U3P01618RT)
    Language English
    Publishing date 2015-09
    Publishing country Ireland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 605646-5
    ISSN 1879-0887 ; 0167-8140
    ISSN (online) 1879-0887
    ISSN 0167-8140
    DOI 10.1016/j.radonc.2015.06.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  10. Article ; Online: Tyk2 as a target for immune regulation in human viral/bacterial pneumonia.

    Berg, Johanna / Zscheppang, Katja / Fatykhova, Diana / Tönnies, Mario / Bauer, Torsten T / Schneider, Paul / Neudecker, Jens / Rückert, Jens C / Eggeling, Stephan / Schimek, Maria / Gruber, Achim D / Suttorp, Norbert / Hippenstiel, Stefan / Hocke, Andreas C

    The European respiratory journal

    2017  Volume 50, Issue 1

    Abstract: The severity and lethality of influenza A virus (IAV) infections is frequently aggravated by secondary bacterial pneumonia. However, the mechanisms in human lung tissue that provoke this increase in fatality are unknown and therapeutic immune modulatory ... ...

    Abstract The severity and lethality of influenza A virus (IAV) infections is frequently aggravated by secondary bacterial pneumonia. However, the mechanisms in human lung tissue that provoke this increase in fatality are unknown and therapeutic immune modulatory options are lacking.We established a human lung
    MeSH term(s) Granulocyte-Macrophage Colony-Stimulating Factor/metabolism ; Humans ; Immunity, Innate/drug effects ; Immunologic Factors ; Influenza A virus ; Influenza, Human/drug therapy ; Influenza, Human/immunology ; Interferons/pharmacology ; Interleukin-1beta/metabolism ; Lung/drug effects ; Pneumonia, Bacterial/drug therapy ; Pneumonia, Bacterial/immunology ; Staphylococcal Infections/drug therapy ; Staphylococcal Infections/immunology ; TYK2 Kinase/antagonists & inhibitors ; TYK2 Kinase/metabolism
    Chemical Substances IL1B protein, human ; Immunologic Factors ; Interleukin-1beta ; Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1) ; Interferons (9008-11-1) ; TYK2 Kinase (EC 2.7.10.2) ; TYK2 protein, human (EC 2.7.10.2)
    Language English
    Publishing date 2017
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639359-7
    ISSN 1399-3003 ; 0903-1936
    ISSN (online) 1399-3003
    ISSN 0903-1936
    DOI 10.1183/13993003.01953-2016
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top