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  • 1
    ISSN: 1573-7373
    Keywords: glioma ; p21 ; p53 ; WAF1 ; CIP1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The p21 gene encodes a cyclin dependent kinase inhibitor protein (p21) which has a tumor suppressive activity in a variety of tumor cell lines. Since, the p21 gene is up-regulated by the p53 tumor suppressor gene, which is frequently mutated in gliomas, acting therefore in the same control pathway, it constitutes a good candidate gene to be also inactivated in these tumors. To test this hypothesis, DNAs from 81 gliomas (48 glioblastomas, 11 anaplastic astrocytomas, 10 low-grade astrocytomas, 12 oligodendrogliomas and mixed gliomas), were investigated for mutations in the p21 coding sequence by denaturant gradient gel electrophoresis followed by sequencing. All these tumors have been previously screened for p53 mutations. Three different DNA variants were identified on codon 31 (17 cases), 27 (1 case) and 117 (1 case) and shown to be also present in matching constitutional DNA, suggesting they were polymorphisms. None of the tumors demonstrated a somatic mutation. No significant correlation between the presence of a p21 variant and the p53 mutation tumor status was observed. In conclusion, mutation in the p21 gene unlikely contributes to the development of gliomas.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Neurofibromatosis type 2 (NF2) is a monogenic dominantly inherited disease predisposing carriers to develop nervous system tumours. To identify the genetic defect, the region between two flanking polymorphic markers on chromosome 22 was cloned and several genes identified. One is the site of ...
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-7373
    Keywords: meningioma ; chromosome 1 ; p18 ; CDKN2C
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract After chromosome 22 and NF2 inactivation, the loss of chromosome 1p is one of the most frequent abnormalities encountered in meningiomas. However the putative tumor suppressor gene located on 1p inactivated in meningiomas has still to be identified. We screened 68 meningiomas for LOH on chromosome 22 and 1. We found 34 LOH on the NF2 region on chromosome 22 (50%) and 19 LOH on 1p (28%), 16 being associated with loss of chromosome 22. Partial deletions delimited a candidate region located between D1S234 and D1S2797. The p18 INK4C tumor suppressor gene, a member of the genes family coding for inhibitors of cyclin-dependent kinases, is located in this region. To determine whether p18 is involved in development of meningiomas, we performed a mutation analysis of the p18 gene and a search for homozygous deletion in the 19 meningiomas with 1p loss. Sequencing analysis of the p18 gene revealed one polymorphism, but no somatic mutations and no homozygous deletions were found. These results confirm that the loss of chromosome 1p32 is a frequent feature in meningiomas, however the p18 tumor suppressor gene which is located in this region, does not seem to be involved.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-7373
    Keywords: malignant gliomas ; elderly ; radiotherapy ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The benefit of standard treatment of malignant glioma in older patients is debated. In order to assess the effect of a combination of surgery, radiotherapy and chemotherapy on survival of elderly patients with high grade gliomas, 30 consecutive patients older than 70 years with malignant supratentorial gliomas were studied between 9/93 and 9/96. Median age was 73 years (70–79). The mean Karnofsky performance status (KPS) was 66 (30–100). Patients underwent maximum possible surgery, followed by a course of radiotherapy (45 Gy/25 fractions/5 weeks) with 3 or 4 orthogonal beams and a 2 cm margin around the tumor bed. The administration of chemotherapy was left at the discretion of the responsible physician and 12 patients received reduced dose nitrosourea-based chemotherapy. The overall median survival was 36 weeks. The median time to progression was 26 weeks. Three months after surgery, 26 patients were alive, 5 were in complete response, 2 in partial response and 10 were stabilized. Pre-radiotherapy KPS was the only significant prognostic factor with a median survival of 40 weeks in patients with KPS ≥70 and 25 weeks when KPS was 〉70 (logrank test, p=0.05). In responding and stable patients (57% of the group) the median KPS was 68 and 66 at 1 and 3 months after the completion of radiotherapy. There was no case of radiotherapy-induced dementia with this regimen. Four out of 12 patients who received chemotherapy, experienced WHO grade 3/4 hematotoxicity. This study suggest that some patients older than 70 years with KPS ≥70 may benefit from the treatment of malignant gliomas with surgery followed by reduced dose of limited field radiotherapy. Further studies are needed to define the most appropriate dose of radiotherapy and to evaluate further the risk/benefit ratio of a reduced dose chemotherapy in this population.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neuro-oncology 43 (1999), S. 287-291 
    ISSN: 1573-7373
    Keywords: primary central nervous system lymphoma ; chemotherapy ; radiotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The optimal treatment for primary central nervous system lymphoma (PCNSL) remains undefined. In this paper, we review the main multi-institutional ongoing protocols for PCNSL. Most of the current protocols evaluate the efficacy of combination high-dose methotrexate-based chemotherapy and brain irradiation in phase II studies. Some trials focus on chemotherapy alone as initial treatment, in order to minimize long-term cognitive sequellae. Because old age appears as a major predisposing factor for combined RT and CT neurotoxicity some specific protocols have been proposed to this particular population.
    Type of Medium: Electronic Resource
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