Journal ArticleDOI
Prognostic factors in malignant glioma: Influence of the overexpression of oncogene and tumor-suppressor gene products on survival
Nikolai G. Rainov,Karl-Ulrich Dobberstein,Hannes Bahn,Hans-Jürgen Holzhausen,Christine Lautenschläger,Volkmar Heidecke,W. Burkert +6 more
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TLDR
In conclusion, the present study identified immunohistochemically detected mdm2-protein overexpression as astatistically significant negative prognostic parameter in patients bearing anaplastic or malignant glioma.Abstract:
Despite the use of multimodal therapy, higher-grade glioma is stilluniformly fatal in the adult population. There is a considerable differencebetween the length of survival in each given patient, even within the sametumor type and malignancy grade group, suggesting that there are factorsthat might differentially influence outcome. To identify such factors, 107patients with anaplastic or malignant glioma were retrospectivelyinvestigated. Clinical parameters and paraclinical data on the p53, mdm2,and EGFR genes at the DNA or protein level were evaluated by univariateanalysis and Cox proportional hazards regression modeling. Kaplan-Meiersurvival estimation demonstrated that immunohistochemical positivity formdm2 protein in patients with anaplastic astrocytoma or with glioblastomamultiforme was associated with a shorter survival time (p = 0.02).P53 gene mutations and immunopositivity for the epidermal growth factorreceptor (EGFR) protein were not significantly related to poor prognosis.The Cox proportional hazards model revealed immunohistochemical positivityfor p53, mdm2, or for both of them, the presence of postoperativeirradiation, and the extent of surgical resection of tumor to be variablessignificantly associated with prolonged survival. EGFR overexpression, ageover 60 years, and Karnofsky performance score below 40 points did notsignificantly shorten survival time. In conclusion, the present studyidentified immunohistochemically detected mdm2-protein overexpression as astatistically significant negative prognostic parameter in patients bearinganaplastic or malignant glioma. Association analysis of variables revealed apossible correlation between mdm2 and p53, which is also consistent with thebiological interaction mode of both proteins in vivo.read more
Citations
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Histological Typing of tumours of the Central Nervous System
TL;DR: A histological classification of CNS Tumours is presented, highlighting the importance of knowing the carrier and removal status of canine coronavirus as a source of infection for humans.
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Analysis of complex relationships between age, p53, epidermal growth factor receptor, and survival in glioblastoma patients.
Martha L. Simmons,Kathleen R. Lamborn,Michelle Takahashi,Pengchin Chen,Mark A. Israel,Mitchel S. Berger,Tony E. Godfrey,Janice Nigro,Michael D. Prados,Susan M. Chang,Fred G. Barker,Kenneth Aldape +11 more
TL;DR: The results suggest that analysis of prognostic markers in GBM is complex, and maximal information may require analysis of subgroups based on age and the status of specific markers such as p53, and suggest a specific group of patients on which to focus promising therapies targeting EGFR.
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EGFR overexpression and radiation response in glioblastoma multiforme.
Fred G. Barker,Fred G. Barker,Martha L. Simmons,Susan M. Chang,Michael D. Prados,David A. Larson,Penny K. Sneed,William M. Wara,Mitchel S. Berger,Pengchin Chen,Mark A. Israel,Kenneth Aldape +11 more
TL;DR: The observed relative radioresistance of some GMs is associated with overexpression of EGFR, and significant relationships were noted between EGFR score and older age and between p53 score or mutation status and younger age.
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MDM2 and prognosis.
Kenan Onel,Carlos Cordon-Cardo +1 more
TL;DR: Data from a number of different tumor types are reviewed for the predictive significance of MDM2 expression, along with evidence for different mechanisms ofMDM2 overexpression in these different tumors.
Journal ArticleDOI
The Pathobiology of Glioma Tumors
TL;DR: The mechanisms that have been implicated in the pathogenesis of the gliomas are reviewed and examples of the cooperative nature of the pathways involved are provided, which may influence the initial therapeutic response and the potential for development of resistance.
References
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The p53 tumour suppressor gene
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The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation
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Axel Ullrich,Lisa M. Coussens,Joel S. Hayflick,Thomas J. Dull,Alane M. Gray,A W Tam,Jeffrey E. Lee,Yosef Yarden,Towia A. Libermann,Joseph Schlessinger +9 more
TL;DR: The complete 1,210-amino acid sequence of the human epidermal growth factor (EGF) receptor precursor, deduced from cDNA clones derived from placental and A431 carcinoma cells, reveals close similarity between the entire predicted ν-erb-B mRNA oncogene product and the receptor transmembrane and cytoplasmic domains.
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Amplification of a gene encoding a p53-associated protein in human sarcomas
TL;DR: Results are consistent with the hypothesis thatMDM2 binds to p53, and that amplification of MDM2 in sarcomas leads to escape from p53-regulated growth control, and this mechanism of tumorigenesis parallels that for virally-induced tumours.
Journal ArticleDOI
Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin
Towia A. Libermann,Harris R. Nusbaum,Nissim Razon,Richard Kris,Irit Lax,Hermona Soreq,Nigel Whittle,Michael D. Waterfield,Axel Ullrich,Joseph Schlessinger +9 more
TL;DR: 4 of 10 primary brain tumours of glial origin which express levels of EGF receptors that are higher than normal also have amplified EGF receptor genes, suggesting that such altered expression and amplification is a particular feature of certain human tumours.