Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors analysed the survival time of 372 patients subjected to radiotherapy after operations for central nervous system tumours of glial origin. Subtentorial gliomas with a better prognosis than supratentorial gliomas accounted for 82% of cases in this group of 67 children, and cerebellar medulloblastoma most sensitive to radiation accounted for 85%. In the group of 305 adults supratentorial tumours were found in 90.8% of cases, and the very malignant multiform glioblastoma was present in 50.8% of cases. In view of these differences the five-year survival rate was 31.3% in children than 40 years; no sex differences were found between the groups with different survival rates. Postoperative radiotherapy of malignant gliomas is of great value prolonging the life of the patients and improving its quality.
Neurol Neurochir Pol
PMID:[Postoperative radiotherapy of glial tumors of the central nervous system]. 261 86

Astrocytomas are the most common tumors of the central nervous system (CNS). Their malignant counterparts, anaplastic astrocytoma and glioblastoma, are lethal neoplasms with poor clinical outcome and they frequently carry mutations of TP53 tumor suppressor gene. In order to determine the frequency and type of this molecular alteration in the Polish population, we analyzed the polymerase chain reaction products corresponding to the most conservative exons 5-8 for single-strand conformation polymorphism and confirmed the presence of mutations by direct DNA sequencing. We identified mutations in one of five (20%) anaplastic astrocytomas and in eight of 28 (29%) glioblastomas; the mutations were most frequently identified in the exon 8 (six glioblastomas). The frequency of TP53 mutations is thus similar to the corresponding data from other studies, and the type of mutations suggests the participation of endogenous etiological factor.
Pol J Pathol 1997
PMID:TP53 mutations in malignant astrocytomas. 952 27

The aim of the study of 41 multiform glioblastomas was the analysis of p53-protein immunoreactivity in neoplastic cells and evaluation of relationship of this biologic marker to tumour proliferation activity. Positive p53 expression was observed in 24 (58.5%) tumours, the negative one in 17 tumours (41.5%). Proliferation indexes of PCNA, anti-Ki6 and AgNORs showed high values in the multiform glioblastoma p53 positive group, but without statistical differences in comparison with the group of p53-negative glioblastomas. Significant differences were observed in survival time of patients with p53 positive tumours in comparison with p53-negative ones. In 15 patients with p53-positive multiform glioblastomas survival time was less than 6 months (62.5%) on the contrary with only 4 patients with similar survival time in p53-negative glioblastoma group (23.5%). Our results suggest that p53 expression in multiform glioblastoma cells, generally considered as the indirect index of p53 suppressor gene, reflects aggressive stadium of neoplastic disease and significantly worsens the prognosis.
Neurol Neurochir Pol
PMID:[Expression of p53 protein and proliferative activity in multiform glioblastoma]. 986 16

We investigated the frequency and mutual relationship of molecular alterations in 33 malignant astrocytomas (28 glioblastomas and 5 anaplastic astrocytomas). The genetic alterations analyzed were: deletion of CDKN2a/p16 gene, TP53 mutations, and amplification of EGFR, MDM2 and CDK4. The most common genetic alteration was EGFR amplification which was revealed in 15 cases (45%). TP53 mutation was identified in 9 cases (27%) and CDKN2/p16 deletion was detected in 13 cases (41%). Either MDM2 and CDK4 amplifications were less frequent, as they were identified in 4 (12%) and 1 (3%) case, respectively. Of the 15 cases showing the amplification of EGFR, 9 had CDKN2/p16 deletion (60%, p = 0.04). On the other hand, CDKN2/p16 deletion and EGFR amplification rarely occurred with TP53 mutations (2 of 14 cases with CDKN2/p16 deletion, 14%). These results confirm the existence of at least two different pathways leading to the formation of a glioblastoma.
Pol J Pathol 1998
PMID:Mutations of TP53, amplification of EGFR, MDM2 and CDK4, and deletions of CDKN2A in malignant astrocytomas. 1032 80

Reactive oxygen species are toxic and cancerogenic factors to living organisms. They are suggested to cause DNA damage (modification) that triggers cancer development. It seems that oxidative damage product 8-oxo-deoxyguanosine (8-oxo-dG) which induces transversion of G to T could be a good chemical marker for cancerogenesis. The aim of our studies was to use 8-oxo-dG as a probe for brain tumour in 17 patients operated on for intracranial neoplasm. Among the patients there were 7 female and 11 male aged from 14 to 60 year. Mean age was 42.88 +/- 16.14 yrs. Several types of tumours were selected histopathologically: from neuroepithelial tissue--6 cases, meningeomas--4, metastases--3, lymphomas--2, neurinoma--1 and chondrosarcoma--1. The tumour tissue was collected from removed material and stored at -20 degrees C. DNA from the neoplastic tissues was isolated by salt method. After hydrolysis of DNA with nuclease P1 and dephosphorylation with bacterial alkaline phosphatase, the mixture of nucleosides was analysed by liquid chromatography method connected with electrochemical detector (HPLC-ECD) working at potential 400 mV. We found higher level of 8-oxo-dG in DNA of patients with malignant tumour (glioblastoma). However, at the present stage of these studies there was no proportional correlation between the level of 8-oxo-dG in DNA in tumour tissue and its malignancy.
Neurol Neurochir Pol
PMID:[8-oxoguanosine as a marker of neoplastic process in brain]. 1079 Oct 36

In human cytomegalovirus (HCMV) infection, both of the major immediate-early proteins IE1(IE68, UL123) and IE2(IE86, UL122) target to PML protein-associated nuclear bodies known as PODs or ND10 at very early times after infection. IE1 causes a redistribution of both PML and IE1 from the PODs into a nuclear diffuse form, whereas IE2 initially localizes adjacent to PODs but later associates with viral DNA replication compartments. The peripheries of PODs are also believed to be sites for initiation of both viral IE transcription and DNA replication. However, because IE1 is nonessential at high multiplicity of infection (m.o.i.) in HF cells, the exact role of these processes in viral infection has been enigmatic. Therefore, we investigated the effects of overexpression of PML in the presence or absence of IE1 on the intranuclear distribution of IE2 and formation of viral DNA replication compartments, as well as on the levels of delayed-early and late viral transcription and protein accumulation. Infection with wild-type HCMV(Towne) and the IE1-deleted derivative HCMV(CR208), which fails to disrupt PODs, was compared in a pair of related astrocytoma/glioblastoma cell lines, the U373-Neo control and a variant U373-PML that constitutively overexpresses PML(560) in much larger than normal PODs. IFA studies on the localization patterns for IE1, IE2, and PML showed that, although the numbers of IE2-positive cells were not significantly reduced in either the wild-type virus-infected U373-PML cell line or in DeltaIE1-infected control cells, POD disruption by IE1 in wild-type virus infection was delayed by up to 6 h in U373-PML cells compared to control cells. Furthermore, there was considerable enhancement of IE2 colocalization with PODs in Delta IE1-infected U373-PML cells. Formation of viral DNA replication compartments in the U373-PML cell line was also greatly delayed, measured at fivefold lower after wild-type virus infection and 12-fold lower after infection with Delta IE1 than in the control cell line at 48 h at an m.o.i. of 1.0. The levels of representative early and late viral proteins detected by Western blotting were suppressed by fivefold and 22-fold at 24 and 72 h, respectively, in the U373-PML cell line, even with high m. o.i. wild-type HCMV infection. Decreased viral protein levels also occurred when control cells were infected with the Delta IE1 virus and these two effects were additive in the U373-PML cell line. Similarly, when U373-PML cells were infected with recombinant HCMV expressing an extragenic luciferase reporter gene under the control of viral early (Pol) or late (pp28) promoters, their transcriptional activation was reduced up to fivefold at both high and low m.o.i. compared to that of the control cells. Overall, these results suggest that POD disruption by IE1 and subsequent redistribution of both PML and IE1 at very early times after infection may play an important role in the efficient utilization of cellular transcription and replication machinery by HCMV and contribute to rapid progression of the HCMV lytic cycle.
 ...
PMID:Disruption of PML-associated nuclear bodies by IE1 correlates with efficient early stages of viral gene expression and DNA replication in human cytomegalovirus infection. 1093 87

Changes in the content and composition of lipids in brain tumours of different degree of malignancy are still the subject of numerous scientific studies. It is known that in developing brain tumours structural and functional changes of its cells, take place, in which lipids play a crucial role. The examination of the lipid spectrum was conducted in a material extracted from tumour adjacent areas (by means of fenestration) as well as from tumours themselves in 11 patients (mean age 56.8 yrs). Based on histological studies all the tumours were qualified as glioblastoma 4th degree of malignancy. Lipids were isolated from the tumours as well as from their adjacent areas. Later on they were separated, using column chromatography and thin-layer chromatography, into three classes: phospholipids, galactolipids and neutral lipids. Separated lipids were subjected to quantitative analysis by spectrophotocolorimetric method. In comparison to adjacent areas, in tumours distinct changes of lipid levels were noticed in all analysed lipid classes. Statistical analysis showed significant decrease of phospholipids (elements stabilizing cell membranes) in tumours in comparison to their adjacent areas (Wilcoxon's test: p < 0.05). At the same time in tumours an increase of level of plasmalogens took place: phosphatidylcholine (PC) (PPC), phosphatidylethanolamine (PE) (PPE) typical elements of malignant tumours, responsible for cross cell membrane transportation processes. This phenomenon was accompanied by changes of levels of PC/PE and PC/SM (sphingomyelin) ratios connected with adhesiveness and other membrane features. Changes in the level of lipids, and phospholipids in particular, in glioblastoma 4th degree of malignancy in comparison to adjacent areas can indicate the pathological processes in cells of these tumours.
Neurol Neurochir Pol
PMID:[Lipid image in glioblastoma multiforme]. 1096 24

Immune response was studied to human glioblastoma with an accumulation of lymphocytes at the tumour site. The anti-tumour activity of the tumour infiltrating lymphocytes was confirmed by results from numerous investigations. The role of lymphocytes in gliomas is still widely discussed. Recent studies suggest a potential role of infiltrating lymphocytes as cellular effectors of angiogenesis. In this paper the authors discuss the immune response abnormalities especially with regard to the role of lymphocytes in angiogenesis.
Neurol Neurochir Pol
PMID:[The role of tumor infiltrating lymphocytes in the immunopathology of gliomas]. 1178 8

There are conflicting reports in connection with the association of the p53 tumour suppressor gene mutation with the clinical and histopathological progression of gliomas. Glia-derived neoplasms frequently show mutational changes in the p53 gene which result in enhancement of tumorigenesis. The aim of the paper was an assessment of the frequency of mutations in the exon 8 of this gene. The specimens from 14 patients operated for glial tumors were investigated by polymerase chain reaction-assisted--single strand conformation polymorphism (PCR-SSCP). We found aberrant bands in 64.3% of specimens. The percentage of mutations was similar in patients with benign and malignant tumours. There was no correlation between the alteration of the gene and intensity of necrosis in histological examination in patients with glioblastoma. Changes in activity of the p53 gene were more frequent in younger patients and in males when compared to women.
Neurol Neurochir Pol 2001
PMID:[Assessment of p53 dependent apoptosis in glia-derived tumors of the brain]. 1193 77

Alterations in the expression of growth factors and their receptors are associated with the growth and development of human tumors. One such growth factor is IGF-I (insulin-like growth factor I ), a 70-amino-acid polypeptide expressed in many tissues, including brain. IGF-I is also expressed at high levels in some nervous system-derived tumors, especially in glioblastoma. When using IGF-I as a diagnostic marker, 17 different tumors are considered as expressing the IGF-I gene. Malignant glioma, the most common human brain cancer, is usually fatal. Average survival is less than one year. Our strategy of gene therapy for the treatment of gliomas and other solid tumors is based on: 1) diagnostic using IGF-I gene expression as a differential marker, and 2) application of "triple-helix anti-IGF-I" therapy. In the latter approach, tumor cells are transfected with a vector, which encodes an oligoribonucleotide--an RNA strand containing oligopurine sequence which might be capable of forming a triple helix with an oligopurine and/or oligopyrimidine sequence of the promotor of IGF-I gene (RNA-IGF-I DNA triple helix). Human tumor cells transfected in vitro become down-regulated in the production of IGF-I and present immunogenic (MHC-I and B7 expression) and apoptotic characteristics. Similar results were obtained when IGF-I antisense strategy was applied. In both strategies the transfected cells reimplanted in vivo lose tumorigenicity and elicit tumor specific immunity which leads to elimination of established tumors.
Acta Biochim Pol 2002
PMID:IGF-I: from diagnostic to triple-helix gene therapy of solid tumors. 1254 4


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