X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    The James Webb Space Telescope Mission
    IOP Publishing ; 2023
    In:  Publications of the Astronomical Society of the Pacific Vol. 135, No. 1048 ( 2023-06-01), p. 068001-
    Details
    In: Publications of the Astronomical Society of the Pacific, IOP Publishing, Vol. 135, No. 1048 ( 2023-06-01), p. 068001-
    Abstract: Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least 4 m. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the 6.5 m James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 yr, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.
    Type of Medium: Online Resource
    ISSN: 0004-6280 , 1538-3873
    URL: Article
    DOI: 10.1088/1538-3873/acd1b5
    Language: Unknown
    Publisher: IOP Publishing
    Publication Date: 2023
    detail.hit.zdb_id: 2003100-2
    detail.hit.zdb_id: 2207655-4
    SSG: 16,12
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 2
    Online Resource
    Online Resource
    Digital shinrin-yoku: do nature experiences in virtual reality reduce stress and increase well-being as strongly as similar experiences in a physical forest?
    Springer Science and Business Media LLC ; 2022
    In:  Virtual Reality Vol. 26, No. 3 ( 2022-09), p. 1245-1255
    Details
    In: Virtual Reality, Springer Science and Business Media LLC, Vol. 26, No. 3 ( 2022-09), p. 1245-1255
    Abstract: Shinrin-yoku or forest bathing refers to a therapeutic, immersive nature experience that aids to improve well-being. The goal of the current research was to compare the effects of a physical urban nature versus virtual nature experience on stress, affect, vitality, and restoration. Previous research suggested that an immersive nature experience—such as shinrin-yoku—can be beneficial for health, but direct comparisons between physical and virtual reality (VR) experiences are scarce. In the current study, fifty participants navigated self-paced through a forest scene that was either an urban physical forest or an immersive VR forest with similar characteristics as the physical one. Before and after the intervention, we measured positive and negative affect, subjective vitality, and perceived daily stress. After the intervention, we measured perceived restorative outcomes. Results revealed that both VR and physical nature experience resulted in expected effects on well-being indicators: Affect was more positive and less negative, subjective vitality increased slightly, and stress decreased slightly after both interventions. There were no significant differences between the two settings on any of the variables, but slightly stronger effect sizes over time within the physical condition. Overall, these findings suggest that immersive VR nature experiences can have restoration effects similar to physical nature experiences, suggesting intervention strategies when physical nature options are scarce.
    Type of Medium: Online Resource
    ISSN: 1359-4338 , 1434-9957
    URL: Article
    DOI: 10.1007/s10055-022-00631-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1481468-7
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 3
    Online Resource
    Online Resource
    A comparison of pediatric inflammatory multisystem syndrome temporarily-associated with SARS-CoV-2 and Kawasaki disease
    Springer Science and Business Media LLC ; 2023
    In:  Scientific Reports Vol. 13, No. 1 ( 2023-01-20)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2023-01-20)
    Abstract: The connection between Pediatric Inflammatory Multisystem Syndrome (PIMS) and Kawasaki Disease (KD) is not yet fully understood. Using the same national registry, clinical features and outcome of children hospitalized in Germany, and Innsbruck (Austria) were compared. Reported to the registry were 395 PIMS and 69 KD hospitalized patients. Patient age in PIMS cases was higher than in KD cases (median 7 [IQR 4–11] vs. 3 [IQR 1–4] years). A majority of both PIMS and KD patients were male and without comorbidities. PIMS patients more frequently presented with organ dysfunction, with the gastrointestinal (80%), cardiovascular (74%), and respiratory (52%) systems being most commonly affected. By contrast, KD patients more often displayed dermatological (99% vs. 68%) and mucosal changes (94% vs. 64%), plus cervical lymph node swelling (51% vs. 34%). Intensive care admission (48% vs. 19%), pulmonary support (32% vs. 10%), and use of inotropes/vasodilators (28% vs. 3%) were higher among PIMS cases. No patients died. Upon patient discharge, potentially irreversible sequelae—mainly cardiovascular—were reported (7% PIMS vs. 12% KD). Despite differences in age distribution and disease severity, PIMS and KD cases shared many common clinical and prognostic characteristics. This supports the hypothesis that the two entities represent a syndrome continuum.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-022-26832-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2615211-3
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 4
    Online Resource
    Online Resource
    Abstract B05: Myxoid liposarcoma: A molecular and clinicopathological analysis by targeted next-generation sequencing and fluorescence in situ hybridization
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 22_Supplement ( 2017-11-15), p. B05-B05
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 22_Supplement ( 2017-11-15), p. B05-B05
    Abstract: Introduction: Myxoid liposarcoma (MLS) is the second most common type of liposarcoma, accounting for 30-35% of all LS cases. Over 90% of tumors are characterized by a reciprocal translocation t (12; 16) (q13; p11), resulting in a pathogenic gene fusion. The chimeric FUS-DDIT3 fusion protein is suggested to play a crucial role in MLS tumorigenesis and progression, although the specific biological function and the mechanism of action remain to be defined. We compiled a comprehensive cohort of 105 well-characterized MLS tissue specimens to identify actionable genetic aberrations. Methods: Targeted next-generation sequencing (NGS) using the Illumina MiSeq platform was performed to examine the mutational status of 23 cancer-related genes (covering all exons) known to be frequently mutated across various neoplasms. Furthermore, we examined the amplification/deletion status and characterized the specific chromosomal FUS-DDIT3 rearrangements by FISH and RT-PCR. A multivariate analysis was conducted to investigate the prognostic significance of mutation/amplification/deletion status. Results: Targeted next-generation sequencing drives the potential to generate comprehensive genetic information including less frequent mutated genes relevant for actionable treatments and prognostic assessment. Besides PIK3CA, six additional genes showed at least five mutations, including AKT1, CTNNB1, EGFR, ERBB2, MET and PTEN. Several oncogenic mutations were detected which have not been reported in MLS previously. We demonstrated several gene amplification/deletion events in MLS. Conclusion: Our results indicate the occurrence of mutational aberrations besides the chromosomal FUS-DDIT3 hallmark. These appear not to be related to specific subtypes of FUS-DDIT3 fusion transcripts in terms of a molecular pattern. Molecular screening for actionable mutations might represent a rational tool for the implementation of innovative targeted therapeutic approaches in MLS. To our best knowledge, this study is the most extensive one to yield a detailed map of actionable genetic aberrations across a comprehensive cohort of & gt;100 well-characterized MLS tissue specimens. Moreover, it reveals several molecular alteration-specific targets for innovative therapy strategies. Citation Format: Marcel Trautmann, Arne Krüger, Birte Jeiler, Christian Bertling, Jasmin Menzel, Magdalene Cyra, Konrad Steinestel, Inga Grünewald, Pierre Åman, Eva Wardelmann, Sebastian Huss, Wolfgang Hartmann. Myxoid liposarcoma: A molecular and clinicopathological analysis by targeted next-generation sequencing and fluorescence in situ hybridization [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B05.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.NEWFRONT17-B05
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 5
    Online Resource
    Online Resource
    Combined Blockade of TIGIT and CD39 or A2AR Enhances NK-92 Cell-Mediated Cytotoxicity in AML
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 23 ( 2021-11-29), p. 12919-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 23 ( 2021-11-29), p. 12919-
    Abstract: This study aimed to characterize different natural killer (NK) cell phenotypes on bone marrow and peripheral blood cells from acute myeloid leukemia (AML) patients and healthy donors (HDs). Our data show that CD56dimCD16− and CD56brightCD16− NK cells represent the predominant NK cell subpopulations in AML, while the CD56dimCD16+ NK cells are significantly reduced compared to HDs. Moreover, TIGIT+ and PVRIG+ cells cluster on the CD56dimCD16+ subset whereas CD39+ and CD38+ cells do so on CD56brightCD16− NK cells in AML. Furthermore, functional effects of (co-)blockade of TIGIT and CD39 or A2AR on NK cell functionality were analyzed. These experiments revealed that the single blockade of the TIGIT receptor results in an increased NK-92 cell-mediated killing of AML cells in vitro. Combined targeting of CD39 or A2AR significantly augments the anti-TIGIT-mediated lysis of AML cells. Our data indicate that distinct NK cell subsets in AML exhibit different immunosuppressive patterns (via the TIGIT/PVRIG receptors and the purinergic pathway). In summary, we conclude that TIGIT, CD39, and A2AR constitute relevant inhibitory checkpoints of NK cells in AML patients. A combinatorial blockade synergistically strengthens NK-92 cell-mediated cytotoxicity. As inhibitors of TIGIT, CD39, and A2AR are clinically available, studies on their combined use could be conducted in the near future.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms222312919
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 6
    Online Resource
    Online Resource
    FUS–DDIT3 Fusion Protein-Driven IGF-IR Signaling is a Therapeutic Target in Myxoid Liposarcoma
    American Association for Cancer Research (AACR) ; 2017
    In:  Clinical Cancer Research Vol. 23, No. 20 ( 2017-10-15), p. 6227-6238
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 23, No. 20 ( 2017-10-15), p. 6227-6238
    Abstract: Purpose: Myxoid liposarcoma is an aggressive disease with particular propensity to develop hematogenic metastases. Over 90% of myxoid liposarcoma are characterized by a reciprocal t(12;16)(q13;p11) translocation. The resulting chimeric FUS–DDIT3 fusion protein plays a crucial role in myxoid liposarcoma pathogenesis; however, its specific impact on oncogenic signaling pathways remains to be substantiated. We here investigate the functional role of FUS–DDIT3 in IGF-IR/PI3K/Akt signaling driving myxoid liposarcoma pathogenesis. Experimental Design: Immunohistochemical evaluation of key effectors of the IGF-IR/PI3K/Akt signaling axis was performed in a comprehensive cohort of myxoid liposarcoma specimens. FUS–DDIT3 dependency and biological function of the IGF-IR/PI3K/Akt signaling cascade were analyzed using a HT1080 fibrosarcoma-based myxoid liposarcoma tumor model and multiple tumor–derived myxoid liposarcoma cell lines. An established myxoid liposarcoma avian chorioallantoic membrane model was used for in vivo confirmation of the preclinical in vitro results. Results: A comprehensive subset of myxoid liposarcoma specimens showed elevated expression and phosphorylation levels of various IGF-IR/PI3K/Akt signaling effectors. In HT1080 fibrosarcoma cells, overexpression of FUS-DDIT3 induced aberrant IGF-IR/PI3K/Akt pathway activity, which was dependent on transcriptional induction of the IGF2 gene. Conversely, RNAi-mediated FUS–DDIT3 knockdown in myxoid liposarcoma cells led to an inactivation of IGF-IR/PI3K/Akt signaling associated with diminished IGF2 mRNA expression. Treatment of myxoid liposarcoma cell lines with several IGF-IR inhibitors resulted in significant growth inhibition in vitro and in vivo. Conclusions: Our preclinical study substantiates the fundamental role of the IGF-IR/PI3K/Akt signaling pathway in myxoid liposarcoma pathogenesis and provides a mechanism-based rationale for molecular- targeted approaches in myxoid liposarcoma cancer therapy. Clin Cancer Res; 23(20); 6227–38. ©2017 AACR.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-17-0130
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 7
    Online Resource
    Online Resource
    Abstract B04: Oncogenic relevance of IGF-IR and PI3K/AKT/GSK3-beta signaling in myxoid liposarcoma
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 22_Supplement ( 2017-11-15), p. B04-B04
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 22_Supplement ( 2017-11-15), p. B04-B04
    Abstract: Introduction: Myxoid liposarcoma (MLS) accounts for 30-35% of all LS cases and is the second most common type of liposarcoma. One third of MLS lesions will become metastatic with tumors spreading to unusual bone and soft tissue locations. Ninety percent of MLS are characterized by a specific reciprocal translocation t (12; 16) (q13; p11), leading to the pathogenic gene fusion of FUS and DDIT3. The resulting chimeric FUS-DDIT3 fusion protein is suggested to play a crucial role in MLS pathogenesis, although the specific biological function and the mechanism of action remain to be defined. Aiming at the preclinical identification of novel therapeutic options in vitro and in vivo, we investigate the functional relevance of IGF-IR and PI3K/AKT/GSK3-beta signaling in primary MLS and tumor-derived cell lines. Methods: Immunohistochemical analyses of IGF-IR and PI3K/AKT/GSK3-beta signaling effectors and modulators were performed in a comprehensive cohort of primary MLS specimens. FUS-DDIT3-dependent activation of the PI3K/AKT/GSK3-beta signaling cascade was analyzed by siRNA knockdown experiments and protein immunoblotting in vitro. Cell proliferation and FACS assays were performed in two different MLS cell lines. An in vivo tumor model was successfully established performing the chicken chorioallantoic membrane (CAM) assay. Results: In a significant subset of MLS specimens, immunohistochemical staining revealed elevated phosphorylation levels of the respective signaling components, indicating that activated IGF-IR and PI3K/AKT/GSK3-beta signaling is a frequent feature in MLS. IGF-IR inhibition significantly suppressed the PI3K/AKT/GSK3-beta downstream cascade, associated with reduced phosphorylation levels of several signaling components, impairment of MLS cell viability and induction of apoptosis in vitro and in vivo. Furthermore, siRNA-mediated knockdown of FUS-DDIT3 lead to dephosphorylation of PI3K/AKT/GSK3-beta signaling components, implying that the FUS-DDIT3 fusion protein is involved in the IGF-IR regulated signaling cascade. Conclusion: Our study emphasizes the pivotal role of IGF-IR and PI3K/AKT/GSK3-beta signaling in MLS pathogenesis and indicates its functional dependence on the characteristic FUS-DDIT3 fusion protein. Furthermore, our in vitro and in vivo results demonstrate that targeting the IGF-IR and PI3K/AKT/GSK3-beta signaling pathway might provide a specific, molecular founded therapeutic strategy in the treatment of MLS. Citation Format: Marcel Trautmann, Christian Bertling, Jasmin Menzel, Magdalene Cyra, Konrad Steinestel, Inga Grünewald, Pierre Åman, Eva Wardelmann, Sebastian Huss, Wolfgang Hartmann. Oncogenic relevance of IGF-IR and PI3K/AKT/GSK3-beta signaling in myxoid liposarcoma [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B04.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.NEWFRONT17-B04
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 8
    Online Resource
    Online Resource
    μ-Mechanical characterization of tribologically stressed elastomer surfaces with respect to radial shaft sealing systems
    Narr Francke Attempto Verlag GmbH + Co. KG ; 2023
    In:  Tribologie und Schmierungstechnik Vol. 70, No. 4-5 ( 2023-09-25), p. 26-31
    Details
    In: Tribologie und Schmierungstechnik, Narr Francke Attempto Verlag GmbH + Co. KG, Vol. 70, No. 4-5 ( 2023-09-25), p. 26-31
    Abstract: This paper introduces the new µ-mechanical characterization method and its application for the post-test radial shaft seal (RSS) analysis of dynamic lubricant-elastomer compatibility tests. Therefore, the measurement procedure and accuracy will be discussed as well as the features which can be drawn from the measured force-displacement curve. Furthermore, it will be shown, how these features allow a precise evaluation of the seal material condition regarding hard deposits, hardening and softening. This will be summarized by showing the correlation of the visual-haptic elastomer assessment and the results of the newly developed characterization method which will increase the informative value of dynamic lubricant-elastomer tests.
    Type of Medium: Online Resource
    ISSN: 0724-3472
    URL: Article
    DOI: 10.24053/TuS-2023-0020
    RVK:
    ZG 1100
    Language: Unknown
    Publisher: Narr Francke Attempto Verlag GmbH + Co. KG
    Publication Date: 2023
    detail.hit.zdb_id: 246052-X
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 9
    Online Resource
    Online Resource
    Tissue-Specific Expression of TIGIT, PD-1, TIM-3, and CD39 by γδ T Cells in Ovarian Cancer
    MDPI AG ; 2022
    In:  Cells Vol. 11, No. 6 ( 2022-03-11), p. 964-
    Details
    In: Cells, MDPI AG, Vol. 11, No. 6 ( 2022-03-11), p. 964-
    Abstract: Phenotypic characterization of γδ T cells in the MALs (malignant ascites lymphocytes), TILs (tumor infiltrating lymphocytes), and PBLs (peripheral blood lymphocytes) of ovarian cancer (OvCA) patients is lacking. Therefore, we quantified γδ T cell prevalence in MAL, TIL, and PBL specimens from n = 18 OvCA patients and PBL from age-matched healthy donors (HD, n = 14). Multicolor flow cytometry was performed to evaluate the expression of inhibitory receptors (TIGIT, PD-1 and TIM-3), stimulatory receptors (Ox40), and purinergic ectoenzymes (CD39 and CD73) on γδ T cell subsets. We identified an abundant infiltration of Vδ1 T cells in the MALs and TILs. These cells varied in their differentiation: The majority of Vδ1 TILs displayed an effector memory (EM) phenotype, whereas Vδ1 MALs had a more mature phenotype of terminally differentiated effector memory cells (TEMRA) with high CD45RA expression. TIGIT and TIM-3 were abundantly expressed in both MALs and PBLs, whereas Vδ1 TILs exhibited the highest levels of PD-1, CD39, and Ox40. We also observed specific clusters on mature differentiation stages for the analyzed molecules. Regarding co-expression, Vδ1 TILs showed the highest levels of cells co-expressing TIGIT with PD-1 or CD39 compared to MALs and PBLs. In conclusion, the Vδ1 T cell population showed a high prevalence in the MALs and primary tumors of OvCA patients. Due to their (co-)expression of targetable immune receptors, in particular TIGIT with PD-1 and CD39 in TILs, Vδ1 T cell-based approaches combined with the inhibition of these targets might represent a promising strategy for OvCA.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells11060964
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2661518-6
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 10
    Online Resource
    Online Resource
    Abstract B04: Functional characterization of IGF-IR/PI3K/Akt signaling in myxoid liposarcoma
    American Association for Cancer Research (AACR) ; 2018
    In:  Clinical Cancer Research Vol. 24, No. 2_Supplement ( 2018-01-15), p. B04-B04
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 24, No. 2_Supplement ( 2018-01-15), p. B04-B04
    Abstract: Introduction: Myxoid liposarcoma (MLS) is the second most common type of liposarcoma and an aggressive disease with particular propensity to develop hematogenic metastases. Ninety percent of MLS are characterized by a reciprocal translocation t(12;16) (q13;p11), leading to the pathogenic gene fusion of FUS and DDIT3. The resulting chimeric FUS-DDIT3 fusion protein is suggested to play a crucial role in MLS pathogenesis, although the specific mechanism of action remains to be substantiated. Aiming at the preclinical identification of novel therapeutic options, we here investigate the functional relevance of FUS-DDIT3 in IGF-IR/PI3K/Akt signal transduction. Experimental Procedures: Immunohistochemical analyses of IGF-IR/PI3K/Akt signaling effectors and modulators were performed in a comprehensive cohort of clinical MLS specimens. FUS-DDIT3-dependent activation of the IGF-IR/PI3K/Akt signaling cascade was analyzed by siRNA and immunoblotting in vitro. Cell proliferation and FACS assays were performed in multiple tumor-derived MLS cell lines. An established MLS chorioallantoic membrane model (CAM) was employed for in vivo confirmation of the preclinical in vitro data. Results: In a significant subset of MLS specimens, immunohistochemical staining revealed elevated phosphorylation levels of various signaling components, representing a strong indication of activated IGF-IR/PI3K/Akt signaling to be a frequent feature in MLS. IGF-IR inhibition significantly suppressed the IGF-IR/PI3K/Akt signaling cascade, associated with impairment of MLS cell viability and induction of apoptosis in vitro and in vivo. Furthermore, siRNA-mediated knockdown of FUS-DDIT3 led to dephosphorylation of IGF-IR/PI3K/Akt signaling components, implying that the FUS-DDIT3 fusion protein is involved in the IGF-IR regulated signaling cascade. Conclusions: Our preclinical study emphasizes the pivotal role of the IGF-IR/PI3K/Akt signaling pathway in MLS pathogenesis and indicates its functional dependence on the MLS-specific FUS-DDIT3 fusion protein. Furthermore, our in vitro and in vivo results demonstrate that targeting the IGF-IR/PI3K/Akt signaling pathway provides a rational, molecularly founded therapeutic strategy in the treatment of MLS. Citation Format: Marcel Trautmann, Magdalene Alice Cyra, Christian Bertling, Ilka Isfort, Jasmin Menzel, Konrad Steinestel, Inga Grünewald, Bianca Altvater, Claudia Rossig, Pierre Åman, Eva Wardelmann, Sebastian Huss, Wolfgang Hartmann. Functional characterization of IGF-IR/PI3K/Akt signaling in myxoid liposarcoma [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr B04.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1557-3265.SARCOMAS17-B04
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
Nothing or not found what you are looking for? Please check your search query or use the Interlibrary Loan Search.
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages