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  • 1
    Language: English
    In: Apoptosis (London), 2006-09, Vol.11 (9), p.1503-1512
    Description: Induction of apoptosis by the death ligand TRAIL might be a promising therapeutic approach in cancer therapy. However, since not all tumor cells are sensitive to TRAIL, there is a need for the development of strategies to overcome TRAIL-resistance. The results of the present study show that the anti-diabetic drug troglitazone sensitizes human glioma and neuroblastoma cells to TRAIL-induced apoptosis. This process is accompanied by a substantial increase of active caspase 8 and active caspase 3, but it is independent of troglitazone's effects on the nuclear receptor PPAR-γ. Troglitazone induces a pronounced reduction in protein expression levels of the anti-apoptotic FLICE-inhibitory protein (FLIP) without affecting FLIP mRNA levels. Further, protein and mRNA expression levels of the anti-apoptotic protein Survivin significantly decrease upon treatment with troglitazone. Moreover, sensitization to TRAIL is partly accompanied by an up-regulation of the TRAIL receptor, TRAIL-R2. A combined treatment with troglitazone and TRAIL might be a promising experimental therapy because troglitazone sensitizes tumor cells to TRAIL-induced apoptosis via various mechanisms, thereby minimizing the risk of acquired tumor cell resistance.
    Subject(s): Biochemistry, general ; Medicine & Public Health ; Brain tumors ; Cancer Research ; Oncology ; Survivin ; FLIP ; Troglitazone ; Virology ; Cell Biology ; Apoptosis ; Receptors, Tumor Necrosis Factor - metabolism ; Inhibitor of Apoptosis Proteins ; Apoptosis - drug effects ; Microtubule-Associated Proteins - metabolism ; Down-Regulation ; Humans ; Neoplasm Proteins - metabolism ; TNF-Related Apoptosis-Inducing Ligand - metabolism ; Antineoplastic Combined Chemotherapy Protocols - pharmacology ; Drug Synergism ; PPAR gamma - physiology ; Thiazolidinediones - therapeutic use ; Caspases - metabolism ; TNF-Related Apoptosis-Inducing Ligand - pharmacology ; Chromans - pharmacology ; Chromans - therapeutic use ; Models, Biological ; Neuroblastoma - drug therapy ; Tumor Cells, Cultured ; Glioblastoma - drug therapy ; Thiazolidinediones - pharmacology ; CASP8 and FADD-Like Apoptosis Regulating Protein - metabolism ; Hypoglycemic agents
    ISSN: 1360-8185
    E-ISSN: 1573-675X
    Source: Alma/SFX Local Collection
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  • 2
    Language: English
    In: Molecular cancer research, 2007-12-01, Vol.5 (12), p.1232-1240
    Description: Glioblastomas, the most malignant of all brain tumors, are characterized by cellular resistance to apoptosis and a highly invasive growth pattern. These factors contribute to the poor response of glioblastomas to radiochemotherapy and prevent their complete neurosurgical resection. However, the driving force behind the distinct motility of glioma cells is only partly understood. Here, we report that in the absence of cellular stress and proapoptotic stimuli, human glioblastoma cells exhibit a constitutive activation of caspases in vivo and in vitro . The inhibition of caspases by various peptide inhibitors decreases the migration of cells in scrape motility assays and the invasiveness of cells in spheroid assays. Similarly, specific small interfering RNA– or antisense-mediated down-regulation of caspase-3 and caspase-8 results in an inhibition of the migratory potential of glioma cells. The constitutive caspase-dependent motility of glioblastoma cells is independent of CD95 activation and it is not mediated by mitogen-activated protein/extracellular signal-regulated kinase kinase signaling. The basal caspase activity is accompanied by a constant cleavage of the motility-associated gelsolin protein, which may contribute to the caspase-mediated promotion of migration and invasiveness in glioblastoma cells. Our results suggest that the administration of low doses of caspase inhibitors that block glioma cell motility without affecting the execution of apoptotic cell death may be exploited as a novel strategy for the treatment of glioblastomas. (Mol Cancer Res 2007;5(12):1232–40)
    Subject(s): migration ; apoptosis ; brain tumors ; invasion ; gliomas ; caspases ; Brain Neoplasms - enzymology ; Glioblastoma - enzymology ; MAP Kinase Signaling System - physiology ; Gelsolin - metabolism ; Neoplasm Invasiveness ; Humans ; Brain Neoplasms - pathology ; Caspase 3 - metabolism ; Caspase 8 - metabolism ; Enzyme Inhibitors - pharmacology ; fas Receptor - metabolism ; Caspase Inhibitors ; Cell Movement - physiology ; Caspase 8 - genetics ; Glioblastoma - pathology ; Caspase 3 - genetics ; Cell Line, Tumor ; RNA, Small Interfering ; Index Medicus
    ISSN: 1541-7786
    E-ISSN: 1557-3125
    Source: HighWire Press (Free Journals)
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 3
    Language: English
    In: ACS applied materials & interfaces, 2018-08-29, Vol.10 (34), p.28803-28811
    Description: In this work, we present a novel small molecule based on dithienylthienothiadiazole units (named SM1) acting as an efficient component in ternary blend organic solar cells to modify the hole extraction at the interface. Our findings show that the SM1 suppresses the surface recombination and enhances the open-circuit voltage (V oc). By introducing SM1 in a host system composed of poly­(3-hexylthiophene) (P3HT) and [6,6]-phenyl-C 61-butyric acid methyl ester (PCBM), we obtained V oc values of up to 0.75 V and fill factors larger than 70% for the ternary blends. As a consequence, the power conversion efficiency is improved by about 30% compared to P3HT:PCBM binary devices. Interestingly, external quantum efficiency and absorption spectra in the near-infrared region do not show any contribution of SM1 in dried films. Instead, the addition of the small molecule improves the V oc by reducing the surface recombination losses. To shed light on the recombination processes, we carried out Fourier-transform photocurrent spectroscopy and impedance spectroscopy measurements. This work shows that the ternary concept can also have functionalities other than photosensitization and can even act as a morphology-directing agent or an interface modifier.
    Subject(s): Research
    ISSN: 1944-8244
    E-ISSN: 1944-8252
    Source: Hellenic Academic Libraries Link
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 4
    Language: English
    In: Brain pathology (Zurich, Switzerland), 2007-04, Vol.17 (2), p.146-150
    Description: About 15% of sporadic gastrointestinal and endometrial tumors show the microsatellite instability (MSI) phenotype because of loss of DNA mismatch repair (MMR) function. The incidence of MSI in tumors of the central nervous system still remains controversial. Previous studies reported a particular high frequency of MSI (∼25%) in young patients suffering from high-grade gliomas. Based on these data and the fact that in different tumor entities MMR deficiency defines a subgroup of tumors with distinct pathogenesis and particular clinicopathological features that may have impact on prognosis and therapy, we screened 624 gliomas from 71 young and 553 adult patients for MMR deficiency by MSI analysis using three highly sensitive diagnostic markers. Alterations of MMR protein expression was examined by immunohistochemistry. A malignant glioma from an adult patient displayed MSI and concomitant loss of nuclear MSH2 and MSH6 protein expression (0.16%; 1/619). No evidence for MSI or loss of MMR protein expression was observed in 71 gliomas from young patients (0%; 0/71) including 41 high-grade astrocytic tumors. Overall, we observed a much lower incidence of MSI among high-grade pediatric gliomas than initially reported and suggest that MMR deficiency does not play a major role in the pathogenesis of glial neoplasms.
    Subject(s): Immunohistochemistry ; Microsatellite Instability ; Humans ; Brain Neoplasms - pathology ; Brain Neoplasms - genetics ; Brain Neoplasms - metabolism ; Glioma - metabolism ; DNA-Binding Proteins - metabolism ; Glioma - genetics ; Glioma - pathology ; Polymerase Chain Reaction ; Adult ; Child ; Pediatrics ; Genetic aspects ; Measles-mumps-rubella vaccine ; Gliomas ; Cancer ; Index Medicus
    ISSN: 1015-6305
    E-ISSN: 1750-3639
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 5
    Language: English
    In: Nature communications, 2020-02-28, Vol.11 (1), p.1114-1114
    Description: Little is known regarding lymph node (LN)-homing of immune cells via afferent lymphatics. Here, we show, using a photo-convertible Dendra-2 reporter, that recently activated CD4 T cells enter downstream LNs via afferent lymphatics at high frequencies. Intra-lymphatic immune cell transfer and live imaging data further show that activated T cells come to an instantaneous arrest mediated passively by the mechanical 3D-sieve barrier of the LN subcapsular sinus (SCS). Arrested T cells subsequently migrate randomly on the sinus floor independent of both chemokines and integrins. However, chemokine receptors are imperative for guiding cells out of the SCS, and for their subsequent directional translocation towards the T cell zone. By contrast, integrins are dispensable for LN homing, yet still contribute by increasing the dwell time within the SCS and by potentially enhancing T cell sensing of chemokine gradients. Together, these findings provide fundamental insights into mechanisms that control homing of lymph-derived immune cells.
    Subject(s): Lymph - cytology ; Lymphocyte Activation ; Receptors, Chemokine - metabolism ; CD4-Positive T-Lymphocytes - metabolism ; Integrins - genetics ; Receptors, Lymphocyte Homing - metabolism ; Lymph Nodes - cytology ; CD4-Positive T-Lymphocytes - physiology ; Integrins - metabolism ; CD4-Positive T-Lymphocytes - immunology ; Cell Movement - immunology ; Animals ; Endothelium, Lymphatic - physiology ; Chemokines - metabolism ; Mice ; Lymph Nodes - physiology ; Receptors, Chemokine - genetics ; Index Medicus ; Lymphatic system ; Lymph node ; Chemokines ; Imaging the immune system
    ISSN: 2041-1723
    E-ISSN: 2041-1723
    Source: Nature Open Access
    Source: PubMed Central
    Source: Directory of Open Access Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 6
    Language: English
    In: GMS. Interdisciplinary plastic and reconstructive surgery DGPW, 2017, Vol.6, p.Doc18
    Description: The reconstruction of extended defects of the concha poses a complex challenge for plastic surgeons. In cases of subtotal ablation, an alternative method designed especially for elderly oncological patients consists of epithetic rehabilitation. However, inserting an implant-retained concha epithesis proves challenging in patients with antecedents of deep resections involving the mastoid process. In the present case study, we report on the long-term treatment course (2009-2017) of a 79-year-old male patient suffering from a recurrent basal cell carcinoma of the retroauricular region. Following tumor resection, along with lateral mastoidectomy, reconstruction, and adjuvant radiotherapy, functional and esthetic deficits primarily due to peripheral facial nerve palsy were successfully managed using a multistep procedure. The procedure was completed by inserting an implant-retained concha epithesis, resulting in improved quality of life. Due to prior lateral mastoidectomy, ultra-short implants (4 mm) were inserted, partially at atypical positions. For maintaining healthy periimplant soft tissue, aftercare comprised cold plasma treatment. This oncologic case demonstrates the therapeutic necessity of using a broad spectrum of reconstructive procedures, along with their limitations, in a critical anatomic region. Specific features include the presentation of a workflow using ultra-short implants in a compromised mastoid region. Surgeons should consider alternative implant positions in the event of any compromised mastoid process. A particular emphasis has been put on meticulous aftercare to preserve healthy periimplant soft tissues.
    Subject(s): auricular ; concha ; craniofacial ; epithesis ; insertion side ; radiotherapy ; basal cell carcinoma ; implant ; mastoid ; tumor resection
    ISSN: 2193-8091
    E-ISSN: 2193-8091
    Source: PubMed Central
    Source: Directory of Open Access Journals
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  • 7
    Language: English
    In: Medical Image Computing and Computer Assisted Intervention – MICCAI 2019, 2019-10-10, p.593-601
    Description: Assessing coronary artery plaque segments in coronary CT angiography scans is an important task to improve patient management and clinical outcomes, as it can help to decide whether invasive investigation and treatment are necessary. In this work, we present three machine learning approaches capable of performing this task. The first approach is based on radiomics, where a plaque segmentation is used to calculate various shape-, intensity- and texture-based features under different image transformations. A second approach is based on deep learning and relies on centerline extraction as sole prerequisite. In the third approach, we fuse the deep learning approach with radiomic features. On our data the methods reached similar scores as simulated fractional flow reserve (FFR) measurements, which - in contrast to our methods - requires an exact segmentation of the whole coronary tree and often time-consuming manual interaction. In literature, the performance of simulated FFR reaches an AUC between 0.79–0.93 predicting an abnormal invasive FFR that demands revascularization. The radiomics approach achieves an AUC of 0.84, the deep learning approach 0.86 and the combined method 0.88 for predicting the revascularization decision directly. While all three proposed methods can be determined within seconds, the FFR simulation typically takes several minutes. Provided representative training data in sufficient quantities, we believe that the presented methods can be used to create systems for fully automatic non-invasive risk assessment for a variety of adverse cardiac events.
    Subject(s): Deep learning ; Plaque characterization ; Computer aided diagnosis ; Coronary CT angiography ; Radiomics
    ISBN: 3030322505
    ISBN: 9783030322502
    ISSN: 0302-9743
    E-ISSN: 1611-3349
    Source: SpringerLINK Lecture Notes in Computer Science (2015)
    Source: Alma/SFX Local Collection
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