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  • 1
  • 2
    Abstract: Morbidity and mortality associated with pediatric malignant primary brain tumors remain high in the absence of effective therapies. Macrophage-mediated phagocytosis of tumor cells via blockade of the anti-phagocytic CD47-SIRPalpha interaction using anti-CD47 antibodies has shown promise in preclinical xenografts of various human malignancies. We demonstrate the effect of a humanized anti-CD47 antibody, Hu5F9-G4, on five aggressive and etiologically distinct pediatric brain tumors: group 3 medulloblastoma (primary and metastatic), atypical teratoid rhabdoid tumor, primitive neuroectodermal tumor, pediatric glioblastoma, and diffuse intrinsic pontine glioma. Hu5F9-G4 demonstrated therapeutic efficacy in vitro and in vivo in patient-derived orthotopic xenograft models. Intraventricular administration of Hu5F9-G4 further enhanced its activity against disseminated medulloblastoma leptomeningeal disease. Notably, Hu5F9-G4 showed minimal activity against normal human neural cells in vitro and in vivo, a phenomenon reiterated in an immunocompetent allograft glioma model. Thus, Hu5F9-G4 is a potentially safe and effective therapeutic agent for managing multiple pediatric central nervous system malignancies.
    Type of Publication: Journal article published
    PubMed ID: 28298418
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  • 3
    ISSN: 0304-4165
    Keywords: (Rat small intestine) ; DAO ; DFMO ; LA ; Lecitin ; ODC ; PHA ; Phytohemagglutinin ; Polyamine uptake ; diamine oxidase ; lactalbumin ; ornithine decarboxylase (EC 4.1.1.17) ; phytohaemagglutinin ; α-difluoromethylornithine
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Aging Studies 4 (1990), S. 359-374 
    ISSN: 0890-4065
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine , Sociology
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1106
    Keywords: C3–C4 Propriospinal neurones ; Forelimb motoneurones ; Intraspinal HRP injections
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Short cervical propriospinal neurones projecting to cat forelimb segments were identified and compared in their longitudinal segmental location and transverse distribution with a propriospinal relay recently described in C3–C4 with electrophysiological methods (Illert et al., 1977, 1978). Localized horseradish peroxidase injections into the C6–C7 forelimb motornuclei demonstrated propriospinal cells in rostral cervical segments. The multiple injection technique in combination with control experiments seemed to allow delimitation of the uptake region in the ventral horn responsible for the retrograde cell labelling. Injections laterally in the ventral horn labelled propriospinal neurones ipsilaterally in C3–C5, mainly in the lateral parts of laminae VI and VII. More medially located injections labelled cells with a similar distribution ipsilaterally, but contralateral cells were found in addition. They were located in laminae VII and VIII of the C2–C5 segments, mainly medially. The evidence is discussed that the neurones located laterally in the C3–C4 segments project directly to ipsilateral forelimb motoneurones and, under this assumption, it is postulated that they constitute the C3–C4 propriospinal relay (Illert et al., 1977) and are identical with the neurones of the “C3–C4 propriospinal system” (Illert et al., 1978).
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1106
    Keywords: Central cervical nucleus ; Cat ; Afferents ; Anterograde degeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Afferent input to the central cervical nucleus (CCN) in the C1–4 segments was studied with degeneration methods after sectioning of dorsal roots (DRs) or lesions in the spinal cord or brain stem. Degeneration in the CCN was heavy after sectioning of the DRs C1–4, moderate after sectioning DRs C5–8, and scanty after sectioning DRs T1–4. One to 2 days after sectioning of the C2 dorsal root the resulting degeneration had a granular appearance. At 4 days after the operation coarser argyrophilic fragments appeared, and this type of degeneration dominated at longer postoperative intervals. Degeneration in the ipsilateral CCN was found after lesions of the ventral and lateral funiculi of the thoracic cord. No degeneration was found after lesions of the dorsal funiculus caudal to T4 or after lesions in the ventral and lateral funiculi of the lumbar cord. Degeneration in the ipsilateral CCN was found after lesions in the brain stem in cases with lesions involving the medial and caudal part of the medulla. These afferents may run in the medial longitudinal fascicle (MLF).
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1106
    Keywords: Cervical enlargement ; Cerebellum ; Termination ; Degeneration ; Autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The cerebellar projection of neurons in the cervical enlargement was investigated in cats using two neuroanatomical methods, the successive degeneration method (Sherrington and Laslett 1903) and the autoradiographic tracing technique (3H-leucine). With both methods projections were found to the anterior lobe, posterior vermis and paramedian lobule. In the anterior lobe the projection was bilateral mainly to the vermal part of lobules I–V and the adjoining part of lobule VI, although some projection was also observed bilaterally to lobules I–VI lateral to the vermis. In the posterior vermis projection was found bilaterally to lobule VIII and in neighboring parts of lobule VII B. In the paramedian lobule the projection was mainly ipsilateral to the lesions/injections to the pars copularis and the adjoining part of the pars posterior. Only minor differences between the two methods were noted. In conclusion, spinocerebellar neurons project mainly to the vermal area of the anterior lobe (including the most anterior part of lobule VI), to lobules VII B and VIII and to the ipsilateral paramedian lobule.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1106
    Keywords: Spinocerebellar neurons ; Cerebellar cortex ; Fluorescent tracers ; Double labeling ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The collateral projections of spinocerebellar neurons located in the L 2 to Ca 1 spinal segments in the cat were investigated by retrograde fluorescent double labeling technique. Rhodamine labeled latex microspheres (Rm) and Fast Blue (FB) were used for injections into the cerebellum in 8 cats. Two additional cats, with injections of Fluoro-Gold (FG) combined with Rm were excluded because lipofuchsin autofluorescence obscured the labeling. After injections with one tracer unilaterally in the paramedian lobule and another tracer bilaterally in the anterior lobe, double labeled neurons were found on the side of the paramedian lobule injection in the column of Clarke at L 2–L 4, laminae IV–VI at L 2–L 5 and the dorsolateral nucleus at L 2–L 6. After bilateral injections of one tracer in lobule VIII B and another in the anterior lobe, double labeled neurons were found bilaterally in the column of Clarke at L 2–L 4, laminae IV–VI at L 2–L 5, the medial part of lamina VII at L 6–L 7 and in certain cell groups at sacro-coccygeal levels. Neurons in the lateral part of lamina VII at L 3–L 5 and the ventrolateral nucleus of L 4–L 5 were labeled exclusively from injections in the anterior lobe. The findings indicate that spinocerebellar neurons at lumbar and more caudal levels of the cat spinal cord have different projection patterns in the cerebellum. A certain number of neurons which project to the anterior lobe have divergent axon collaterals supplying also the posterior vermis and/or the paramedian lobule. Other neurons project to the anterior or to the posterior lobe only.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-1106
    Keywords: Spinocerebellar neurons ; Cerebellar peduncles ; Axonal course ; Horseradish peroxidase ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Among the newly discovered spinocerebellar cell groups, those at lumbar and more caudal levels of the cat's spinal cord were studied with regard to which of the two cerebellar peduncles, the restiform body or the superior cerebellar peduncle, is used by their axons. Bilateral injections with horseradish peroxidase were made into either of the anterior lobe or the posterior cerebellar termination area for spinocerebellar fibers, following unilateral transections of either the superior cerebellar peduncle or the restiform body, combined with low contralateral transections of the lateral and ventral funiculi. Following transection of the superior cerebellar peduncle, labeled neurons were found ipsilateral to the transection in the column of Clarke and in laminae IV–VI at L 3–L 7. Contralaterally, labeled neurons were found in the ventromedial nucleus and lamina VIII of the ventral horn in the sacro-coccygeal segments and in the medial part of lamina VII at L 6 and more caudal levels. All these neurons were regarded as sending their axons through the restiform body. Following transection of the restiform body, labeled neurons were found in the following areas contralateral to the transection: the dorsolateral nucleus of the L 3–L 6 segments, the lateral part of lamina VII at L 3–L 5/6, the medial part of lamina VII in L 6 and more caudal segments, and the ventrolateral nucleus of L 4–L 5. Ipsilaterally, labeled neurons were found in lamina VIII at L 4–L 6. All these neurons were regarded as sending their axons through the superior cerebellar peduncle. In addition to new information about the peduncular routes of spinocerebellar neurons, the study has given confirming evidence as to the crossing conditions for different spinocerebellar cell groups. The findings should be useful in future studies on the organization of the spinocerebellar systems.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1106
    Keywords: Cutaneous nerve projections ; Dorsal horn ; Clarke's column ; Choleragenoid ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of the present study has been to investigate the spinal projections of cutaneous hindlimb afferents particularly to the deep dorsal horn and to Clarke's column (CC), by using the B-subunit of cholera toxin conjugated to horseradish peroxidase. Injections into three different cutaneous hindlimb nerves in adult rats resulted in dense labeling in the dorsal horn laminae IIi-IV/V, moderate labeling in lamina I and modest labeling in dorsomedial parts of CC. Footpad injections gave similar results, except for a lack of labeling in CC and only weak labeling in laminae I and V. The results suggest that B-HRP should be a useful marker for studying cutaneous myelinated nerve fiber projections to the rat spinal cord.
    Type of Medium: Electronic Resource
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