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  • 1
    Keywords: CELL LUNG-CANCER ; FOLLOW-UP ; brain metastases ; ADJUVANT CHEMOTHERAPY ; EGFR MUTATIONS ; TARGETED THERAPIES ; CLINICAL-PRACTICE GUIDELINES ; OPEN-LABEL ; HER2-POSITIVE BREAST-CANCER ; MUTATION-POSITIVE MELANOMA
    Abstract: Metastases to the central nervous system (CNS) are common in several cancer types. For most primary tumors that commonly metastasize to the CNS, molecular biomarker analyses are recommended in the clinical setting for selection of appropriate targeted therapies. Therapeutic efficacy of some of these agents has been documented in patients with brain metastases, and molecular testing of CNS metastases should be considered in the clinical setting. Here, we summarize the clinically relevant biomarker tests that should be considered in neurosurgical specimens based on the current recommendations of the European Society of Medical Oncology (ESMO) or the National Comprehensive Cancer Network (NCCN) for the most relevant primary tumor types: lung cancer (EGFR mutations, ALK rearrangement, BRAF mutations), breast cancer (HER2 amplification, steroid receptor overexpression), melanoma (BRAF mutations), and colorectal cancer (RAS mutations). Furthermore, we discuss emerging therapeutic targets including novel oncogenic alterations (ROS1 rearrangements, FGFR1 amplifications, CMET amplifications, and others) and molecular features of the tumor microenvironment (including immune-checkpoint molecules such as CTLA4 and PD-1/PD-L1). We also discuss the potential role of advanced biomarker tests such as next-generation sequencing and "liquid biopsies" for patients with CNS metastases.
    Type of Publication: Journal article published
    PubMed ID: 25287912
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  • 2
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  48. Jahrestagung der Deutschen Gesellschaft der Plastischen, Rekonstruktiven und Ästhetischen Chirurgen (DGPRÄC), 55. Jahrestagung der Österreichischen Gesellschaft für Plastische, Ästhetische und Rekonstruktive Chirurgie, 22. Jahrestagung der Vereinigung der Deutschen Ästhetisch-Plastischen Chirurgen (VDÄPC); 20170914-20170916; Graz, Österreich; DOC239 /20170816/
    Publication Date: 2017-08-16
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 3
    facet.materialart.
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  45. Jahrestagung der Deutschen Gesellschaft der Plastischen, Rekonstruktiven und Ästhetischen Chirurgen (DGPRÄC), 19. Jahrestagung der Vereinigung der Deutschen Ästhetisch-Plastischen Chirurgen (VDÄPC), 52. Jahrestagung der Österreichischen Gesellschaft für Plastische, Ästhetische und Rekonstruktive Chirurgie (ÖGPRÄC); 20140911-20140913; München; DOC375 /20140903/
    Publication Date: 2014-09-04
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 4
    Keywords: CANCER ; CELLS ; GROWTH ; tumor ; CELL LUNG-CANCER ; ENDOTHELIAL GROWTH-FACTOR ; PHASE-I ; THERAPY ; prognosis ; NUDE-MICE ; MIGRATION ; CENTRAL-NERVOUS-SYSTEM ; INTRACRANIAL METASTASES ; brain metastases ; HUMAN BREAST-CANCER ; MELANOMA-CELLS ; FACTOR EXPRESSION ; Molecular targets ; CLINICAL-PRACTICE GUIDELINE ; Pathobiology
    Abstract: Brain metastases (BM) are common in cancer patients and are associated with high morbidity and poor prognosis, even after intensive multimodal therapy including resection, radiotherapy (stereotactic radiosurgery or whole brain radiotherapy) and chemotherapy. However, advances in the understanding of the pathobiology of BM and the development of molecular targeted agents hold promise for improved prophylaxis and therapy of BM. Here we provide a comprehensive review of the current concepts on mechanisms of the brain-metastatic cascade involving hematogenous dissemination of tumor cells, attachment to microvessel endothelial cells, extravasation into the brain, interaction with the local microenvironment, angiogenesis and intraparenchymal proliferation. Transendothelial migration depends on adhesion molecules such as integrins, selectins and chemokines. Tumor cells invade the brain by degrading extracellular matrix components using heparanase and matrix metalloproteinases. Astrocytes and microglial cells exert not only anti-, but also pro-neoplastic effects on brain-invading tumor cells. Some tumor types (e.g. melanoma) show prominent cooption of preexisting vasculature, while other tumor types (e.g. lung cancer) tend to show early angiogenesis after brain invasion. In this article we also critically summarize the data on currently studied targeted therapeutics in BM especially in the context of recent preclinical data. The most promising agents for BM patients include anti-angiogenic drugs, inhibitors of v-RAF murine sarcoma viral oncogene homolog B1 (BRAF) for BRAF V600E mutated melanoma and inhibitors of epithelial growth factor receptor for non-small cell lung cancer. Molecular analysis of the BRAF V600E status of melanoma BM using DNA-based methods or immunohistochemistry may soon enter the routine neuropathological practice.
    Type of Publication: Journal article published
    PubMed ID: 22212630
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  • 5
    Abstract: Background: We aimed to investigate the potential of standard hematologic and serum biochemical parameters to provide an independent and substantial contribution to the prediction of survival in patients with newly diagnosed brain metastases (BM). Methods: Hemoglobin, white blood cell count, platelet count, serum albumin, creatinine, lactate dehydrogenase (LDH), and C-reactive protein (CRP) were assessed at diagnosis of BM in a discovery cohort of 1200 cancer patients. A multivariable Cox regression model was used to derive the LabBM score. The LabBM score was externally validated in an independent cohort consisting of 366 patients. Results: Hemoglobin below lower limit of normal (〈LLN; hazard ratio [HR] 1.28; P = .001), platelet count 〈LLN (HR: 1.36; P = .013), albumin 〈LLN (HR: 1.19; P = .038), LDH above upper limit of normal (〉ULN; HR: 1.51; P 〈 .001), and CRP 〉ULN (HR: 1.52; P 〈 .001) were associated with survival in a multivariable Cox regression model and were included in the calculation of the LabBM score. Multivariable analysis including the LabBM score and graded prognostic assessment class revealed an independent and significant association of the LabBM score with overall survival (OS) (HR: 1.42; 95% CI: 1.29-1.57; P 〈 .001). The strong and independent association of LabBM score (HR: 1.93; 95% CI: 1.54-2.42) with OS prognosis was confirmed in the validation cohort. Conclusion: Standard clinical blood parameters, combined in the easy-to-calculate LabBM score, provide strong and independent prognostic information in patients with BM. The LabBM score is an objective, inexpensive, and reproducible tool to plan clinical management strategies in BM patients and to improve patient selection and stratification for clinical trials.
    Type of Publication: Journal article published
    PubMed ID: 28096493
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  • 6
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Polyhedron 8 (1989), S. 2407 
    ISSN: 0277-5387
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0277-5387
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1246
    Keywords: Hearing loss, social ; Hearing loss, noise-induced ; Audiometry ; Noise levels ; Hearing ranges
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We investigated a total of 537 subjects (68 men, 469 women) working in the textile industry to ascertain their hearing level in the conventional hearing range as well as in the high-frequency (HF) range. The persons we tested work at three different noise-levels [80–84, 85–89, 90–94dB (A), measured as leq). The differences in the hearing thresholds between this three groups mentioned were checked by means of discriminant analysis. The first hearing level changes at a noise-level below 90 dB (A) leq develop mainly in the HF range. In the conventional hearing range, however, the hearing levels remain unchanged even over long exposure times. Noise-induced hearing loss in the conventional range occurs only in the sound level group of 90 to 94 dB (A) leq without attaining any social importance. The tests show that, if the noise-level 90 dB (A) leq is not exceeded, no noise-induced hearing impairments involving social hearing loss are to be observed. Thus we assume that an auditory risk criterion of 85 dB (A) leq is sufficient to prevent hearing loss of any social importance.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-072X
    Keywords: Bacterial sulfur oxidation ; Cytochromes c ; Bacterial taxonomy ; Electron transfer proteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Four cytochromes were isolated from soluble extracts of the aerobic sulfur bacterium, Thiobacillus neapolitanus. The two most abundant proteins were purified to homogeneity and thoroughly characterized. Cytochrome c-554 (547) is a monomeric, small molecular weight protein which is unusual in having two well-resolved alpha peaks in UV-visible absorption spectra. The redox potential is 208 mV. Native cytochrome c-549 is oligometric, but has a subunit size of about 26.000. The yield of this protein could be improved dramatically by washing membranes with 30% ammonium sulfate, but the material solubilized by this method had a larger native molecular weight than that in the initial 0.1 M Tris-Cl extract and behaved differently on chromatography. The properties of cytochrome c-549 including subunit size and UV-visible absorption spectra are similar to mitochondrial cytochrome c 1 and chloroplast cytochrome f, which suggests that it may be a modified form of the predominant membrane cytochrome. Based on cytochrome content, it is suggested that T. neapolitanus is not closely related to other thiobacilli.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Baker and confectioner apprentices have been included in a prospective follow-up study in the region of East Thuringia, to evaluate risk factors for the development of hand dermatitis. Starting in August 1996, the apprentices have been interviewed and examined in a standardized way right at the beginning (n=91) of their vocational training, 6 (n=79) and 12 months (n=63) later. To gain objective data, TEWL score was also assessed at 3 standardized sites on the hands. In their case histories, 3.3% (n=3) of the apprentices reported hand dermatitis. The 1st assessment after 2 to 4 weeks vocational training revealed hand eczema in 17.5% (n=16) of the individuals. At the follow-up after 6 months of training 29.1% (n=23), and after 12 month of training 27.0% (n=17), of the apprentices had hand dermatitis of mild to moderate severity. Within 6 months, the TEWL score rose significantly (p〈0.001) from 11.9 g m−2 h−1 (± 5.4) to 16.8 g m−2 h−1 (± 9.5). After 12 months, the TEWL score was 14.9 g m−2 h−1 (± 4.6). For the atopic skin diathesis (〉 10 points of Diepgen's atopy score), there was a significant tendency to be a predictive factor for the development of occupational hand dermatitis. TEWL score failed to correlate with the development of skin damage in our study. The same was true for respiratory atopy and metal sensitization.
    Type of Medium: Electronic Resource
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