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  • 1
    ISSN: 1432-0533
    Keywords: Glial fibrillary acidic protein ; Vimentin ; Immunohistochemistry ; Ethylnitrosourea ; Rat Gliomas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The expression of glial fibrillary acidic protein (GFAP) and vimentin was investigated immuno-histochemically in 104 experimental gliomas induced by transplancental application of ethylnitrosourea (ENU) in CDF rats. Immunoreactivity for vimentin was prominent in many astrocytic tumor cells and especially in small glioma cells forming anaplastic medulloblastoma-like foci in many tumors. The majority of tumor cells in oligodendroglial tumors were vimentin negative, except for some of the large polymorphous oligodendrogliomas which contained intermingled vimentin positive glioma cells. GFAP immunoreactivity was detectable only in a low fraction of tumor astrocytes and in a few exceptional cases some oligodendroglial tumor cells stained positive. Immunohistochemistry with antibodies against neurofilaments and cytokeratins revealed no staining in tumor cells of ENU-induced gliomas, while all oligoden-drogliomatous tumors stained positive for HNK-1. Immunocytological and immunoblot investigations of the two rat glioma cell clones RG2 and F98, which are both derived from ENU-induced gliomas, showed a prominent expression of vimentin in monolayer cultures and in syngeneic intracerebral transplantation tumors. F98 additionally demonstrated a fraction of GFAP positive cells especially in confluent cultures and in intracerebral tumors. RG2, on the other hand, exhibited virtually no GFAP immunoreactivity in culture but showed individual GFAP positive tumor cells in intracerebral tumors. Our results revealed a more precise picture of the cellular differentiation in ENU-induced rat gliomas and in two widely used glioma cell lines. They underline the heterogeneity of experimental rat gliomas which may comprise cells at different stages of differentiation towards the oligodendroglial or astroglial phenotype.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 85 (1993), S. 227-232 
    ISSN: 1432-0533
    Keywords: Neurofibromatosis ; Hypertrophic neuropathy ; Schwann cells ; Neurinoma ; Proliferative activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case of symmetrical neurofibroma with onion bulbs in various stages of development and progression to microneurinomas is presented. Immunohistochemistry with differentiation and growth factor markers as well as electron microscopy showed a Schwann cell origin of the concentrically arranged cells. The onion bulbs differed from those of hypertrophic neuropathy by their more compact structure. A partial expression of cellular proliferation markers in the onion bulbs was consistent with a multifocal proliferative activity, confirming the neoplastic nature of the lesion.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0533
    Keywords: Protein kinase C ; Proliferative activity ; Immunohistochemistry ; Human brain neoplasms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Protein kinase C (PKC), the major receptor for phorbol ester tumor promotors, is a phospholipid- and calcium-dependent phosphorylating enzyme which plays an important role in the intracellular signal transduction necessary for a variety of basic cellular functions including the control of cell proliferation. To determine the expression of PKC in human neurogenic tumors we investigated 121 tumors of the human nervous system by means of immunohistochemistry using the monoclonal antibody C5. The results were compared with immunohistochemical staining for intermediate filament proteins, desmoplakins, and the proliferation-associated nuclear antigen Ki-67. Besides strong staining of normal and reactive astrocytes, C5 immunoreactivity was consistently observed in tumor cells of all types of gliomas. However, the fraction of C5 positive tumor cells varied between the different tumor types with astrocytomas and subependymomas demonstrating the strongest immunoreactivity. In the other gliomas, especially those of higher malignancy, a considerable heterogeneity in C5 expression could be observed. There was a tendency for the percentage of C5 immunostained tumor cells being lower in high-grade gliomas compared to low-grade ones and comparison with Ki-67 staining frequently revealed an inverse relationship between proliferative activity and C5 immunoreactivity. Besides the gliomas we found 3 of 7 neurinomas and 6 of 18 meningiomas which were partially C5 positive. All other tumors investigated including medulloblastomas and metastatic carcinomas were C5 negative. Our results thus indicate that immunohistochemistry for PKC using the monoclonal antibody C5 could be an useful aid for histopathological tumor classification in neurooncology.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0533
    Keywords: Ethylnitrosourea-induced neurinomas ; RN6 neurinoma cell line ; Transplantation tumors ; Immunohistochemistry ; Intermediate filaments
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The expression of glial fibrillary acidic protein (GFAP), vimentin, S-100 protein (S-100), HNK-1, myelin basic protein (MBP) and fibronectin was investigated immunohistochemically in 51 ethylnitrosourea (ENU)-induced neurinomas of the rat. Additionally, 90 transplantation tumors derived from ENU-induced neurinomas and the RN6 rat neurinoma cell clone were studied. Vimentin immunoreactivity was shown in 50/51 primary neurinomas and 60/90 transplantation tumors. In contrast, GFAP was expressed in only 23/51 primary tumors and in 5/90 transplantation tumors. In the RN6 neurinoma clone, vimentin and GFAP could be demonstrated both in vivo and in vitro GFAP expression varied depending on the tumor localization, i.e., tumors of distal portions of peripheral nerves were more frequently GFAP positive than tumors of the spinal roots or of cranial nerves. The same tendency was observed for S-100. In the series of transplantation tumors S-100 and GFAP immunoreactivity decreased with increasing numbers of transplantation passages. Only individual cells in 5 primary tumors were HNK-1 positive and no MBP-immunorcactive cells were observed. Our results demonstrate that the expression of differentiation antigens in ENU-induced experimental neurinomas parallels the results reported for human neurinomas.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0533
    Keywords: Immunohistochemistry ; Nervous system tumors ; HNK-1 ; Glial fibrillary acidic protein (GFAP) ; Vimentin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The immunoreactivity of a panel of poly-and monoclonal antibodies raised against different glial and neuronal antigens was investigated in paraffin-embedded specimens of 116 human tumors of the central and peripheral nervous system. We used antibodies against the HNK-1 epitope, which is shared between natural killer cells and the nervous system, glial fibrillary acidic protein (GFAP), vimentin, neurofilaments, S-100 protein, neuron-specific enolase (NSE) and myelin basic protein (MEP). HNK-1 immunoreactivity was detectable in nearly all neuroectodermal tumors. Especially in those derived from the neuroepithelium, which include the various types of gliomas, we observed a strong staining with this antibody. The only exceptions were the choroid plexus papillomas and individual ependymomas. In tumors derived from the neural crest HNK-1 reactivity was more variable and less intense. In other tumors of the nervous system HNK-1 was not detectable, except for two out of four malignant lymphomas. In addition to its reactivity with human lymphocytes HNK-1, therefore, seems to be a useful ‘marker’ for neurogenic tumors in general. GFAP expression was prominent in all astrocytomas and the astrocytic cells within mixed gliomas and gangliogliomas. Immunoreactivity was more variable in glioblastomas and ependymomas, while only isolated GFAP-positive cells were present in oligodendrogliomas, medulloblastomas, one plexus papilloma, and some neurinomas. Vimentin immunoreactivity was found in tumor cells of nearly all tumors of the central nervous system with the exception of oligodendrogliomas, most plexus papillomas, neuronal tumors and most medulloblastomas. Meningeomas, neurinomas and malignant melanomas were always strongly vimentin positive. Besides the tumor cells the vimentin antibody usually stained vascular elements within each tumor. Sarcomatous components in glioblastomas and desmoplastic areas in medulloblastomas were also labeled. Neurofilament expression was restricted to neuronal tumor cells in two gangliogliomas and to individual tumor cells in one medulloblastoma. The NSE antiserum showed more widespread and sometimes diffuse reactivity and, therefore, seems to be less valuable as an indicator for neuronal differentiation than neurofilaments. S-100 expression was demonstrable in numerous tumors including most gliomas and all tumors derived from the neural crest. MBP antibodies never showed reactivity with oligodendroglioma or neurinoma tumor cells. This antibody labeled only myelin sheaths and their remnants within these tumors. Based upon our results we can conclude that, despite the fact that most of the investigated antigens showed a widespread distribution among different tumors, each of them and especially their differential expression might be useful in the classification and differential diagnosis of human tumors of the nervous system.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0942-0940
    Keywords: Metastasis ; carcinoma ; glioma ; immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Metastatic spreading of carcinoma into a pre-existing cerebral glioma is extremely rare and only a few well-documented cases have been reported in the literature. Here we report a 53-year-old man who at the age 49 was first operated on for a frontal astrocytoma (WHO-grade II). This tumour was completely resected and no post-operative radio- or chemotherapy was applied. About five years later the patient presented again with a large partially cystic space-occupying lesion at the same site, which pre-operatively appeared as a recurrence of the astrocytoma. Histologically, however, this tumour proved to be a metastatic adenocarcinoma into a recurrent astrocytoma. Further clinical examinations revealed a bronchial carcinoma as the primary lesion responsible for this unusual metastatis. The clinical and neuropathological findings of this interesting case including immunohistochemistry are presented and discussed.
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 148 (2003), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary We report a 54-year-old woman with Cowden's disease (CD) who was found to carry a novel germline mutation in the PTEN gene. The mutation (c.334C→G) introduced a splice donor site within exon 5 that caused the expression of an aberrant transcript lacking 159 nucleotides corresponding to codons 112–164. Clinically, the patient showed multiple benign hamartomatous lesions of the skin, papillomatosis of the lips and oral mucosa, polyposis coli and bilateral fibrocystic disease of the breast. In addition, she developed different types of malignant neoplasms, including bilateral carcinomas of the breast and malignant melanomas of the skin. Molecular genetic analysis of a benign skin hamartoma and an invasive ductal breast carcinoma revealed loss of heterozygosity (LOH) at microsatellite markers on chromosome 10 in the carcinoma but not in the hamartoma. The breast carcinoma additionally carried a somatic TP53 point mutation (c.466C→G; R156G) that was associated with LOH on 17p and nuclear p53 protein accumulation. Taken together, our findings indicate that benign hamartomas in CD may develop without loss of the second (wild-type) PTEN allele, whereas the pathogenesis of malignant tumours, such as breast carcinomas, appears to require the complete inactivation of Pten as well as further alterations such as the loss of p53-dependent growth control.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  Basal cell carcinoma (BCC) of the skin is the most common human cancer. The genetic alterations underlying BCC development are only partly understood.Objectives  To investigate further the molecular genetics of sporadic BCCs, we performed mutation analyses of 10 skin cancer-associated genes in 42 tumours.Methods  Single-strand conformational polymorphism analysis followed by DNA sequencing was used to screen for mutations in the sonic hedgehog pathway genes PTCH, SMOH, SUFUH and GLI1, in the TP53 tumour suppressor gene, and in the proto-oncogenes NRAS, KRAS, HRAS, BRAF and CTNNB1. Microsatellite markers flanking the PTCH, SUFUH and TP53 loci at 9q22, 10q24 and 17p13, respectively, were studied for loss of heterozygosity (LOH).Results  PTCH mutations were found in 28 of 42 tumours (67%). Microsatellite analysis revealed LOH on 9q22 in 20 of 38 tumours investigated (53%), including 14 tumours with and six tumours without PTCH mutations. SMOH mutations were identified in four of the 42 BCCs (10%) while two tumours demonstrated mutations in SUFUH, including one missense mutation and one silent mutation. None of the BCCs showed LOH at markers flanking the SUFUH locus. Seventeen BCCs (40%) carried TP53 mutations, with only three tumours showing evidence of biallelic TP53 inactivation. TP53 mutations were present in BCCs with and without mutations in PTCH, SMOH or SUFUH. Interestingly, 72% of the TP53 alterations were presumably ultraviolet (UV)-induced transition mutations. In contrast, only 40% of the PTCH and SMOH alterations corresponded to UV signature mutations. No mutations were identified in GLI1, NRAS, KRAS, HRAS, BRAF or CTNNB1.Conclusions  Our data confirm the importance of PTCH, SMOH and TP53 mutations in the pathogenesis of sporadic BCCs. SUFUH alterations are restricted to individual cases while the other investigated genes do not appear to be important targets for mutations in BCCs.
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  • 9
    ISSN: 1432-2307
    Keywords: Brain neoplasms ; Growth fraction Ki-67 ; Epidermal growth factor receptor ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 100 tumours of the human nervous system were investigated by means of immunohistochemistry in order to determine the expression of epidermal growth factor receptor (EGFr) and the proliferative activity as evaluated by demonstration of the proliferation-associated Ki-67 antigen. Epidermal growth factor receptor immunoreactivity was present in 79% (23/29) of the high-grade malignant gliomas examined but in only 9% (2/22) of the low-grade gliomas. Besides the gliomas, EGFr-expression was detectable in smaller amounts in most (13/15) meningiomas, in one anaplastic neurinoma and in individual tumour cells of one medulloblastoma. In addition, EGFr-expression was found in 50% (6/12) of metastatic carcinomas. Seven of eight medulloblastomas, two cerebral primitive neuroectodermal tumours (PNETs), three benign neurinomas, one ganglioneuroma, one metastatic intracerebral malignant melanoma, three spinal plasmocytomas and one immunocytoma showed no detectable EGFr-expression. Our results indicate that (1) the expression of EGFr in human tumours of the nervous system depends on the histological tumour type and (2) in the glioma group is related to the grade of malignancy. A close correlation between EGFrexpression and proliferative activity as evaluated by Ki-67 staining could not, however, be established.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Der Onkologe 6 (2000), S. 919-929 
    ISSN: 1433-0415
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Metastasen bösartiger Neoplasien anderer Organe sind die häufigsten Tumoren des zentralen Nervensystems (ZNS) bei Patienten im mittleren und höheren Lebensalter. Im Regelfall treten ZNS-Metastasen in fortgeschrittenen Stadien der Tumorerkrankung auf. Bei einigen Patienten können aber bereits bei der Erstdiagnose eines malignen Tumors, z. B. eines Bronchialkarzinoms, klinisch asymptomatische Metastasen mittels Computertomographie (CT) oder Kernspinresonanztomographie (MRT) im Gehirn nachgewiesen werden. Schließlich gibt es nicht wenige Patienten, die erstmalig aufgrund einer ZNS-Metastasierung symptomatisch werden, d. h. bei denen der Primärtumor zum Zeitpunkt der Diagnose der Metastase noch unbekannt ist. Insgesamt handelt es sich bei den Metastasen im ZNS um eine sehr heterogene Gruppe bösartiger Tumoren unterschiedlichen Ursprungs. Am häufigsten sind Metastasen von Karzinomen im Bereich der Lunge, der Brustdrüse, des Kolons und der Niere sowie Metastasen von malignen Melanomen der Haut und Schleimhäute. Im folgenden Beitrag möchten wir einen kurzen Überblick über wesentliche Aspekte der Neuropathologie von Metastasen im ZNS geben, wobei insbesondere auf neue Entwicklungen in der histopathologischen und immunhistochemischen Diagnostik eingegangen wird. Ein zweiter Schwerpunkt unseres Beitrages liegt auf den aktuellen Forschungsergebnissen zur Pathogenese und Molekulargenetik dieser Tumoren.
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