Therapeutic inhibition of the epidermal growth factor receptor in high-grade gliomas: where do we stand?

High-grade gliomas account for the majority of intra-axial brain tumors. Despite abundant therapeutic efforts, clinical outcome is still poor. Thus, new therapeutic approaches are intensely being investigated.

Candidate genes for sensitivity and resistance of human glioblastoma multiforme cell lines to erlotinib. Laboratory investigation.

Object: The authors have previously reported that erlotinib, an EGFR tyrosine kinase inhibitor, exerts widely variable antiproliferative effects on 9 human glioblastoma multiforme (GBM) cell lines in vitro and in vivo. These effects were independent of EGFR baseline expression levels, raising the possibility that more complex genetic properties form the molecular basis of the erlotinib-sensitive and erlotinib-resistant GBM phenotypes. The aim of the present study was to determine candidate genes for mediating the cellular response of human GBMs to erlotinib.

Pathogenetic pathways leading to glioblastoma multiforme: association between gene expressions and resistance to erlotinib.

Background: The antiproliferative effects of erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, on human glioblastoma multiforme (GBM) cell lines in vitro and in vivo are widely variable and independent of EGFR baseline expression levels, indicating that more complex genetic signatures may form the molecular basis of GBM response to erlotinib. This study sought to determine which genes within two common genetic pathways of GBM pathogenesis, i.e.

Epidermal growth factor receptor pathway gene expressions and biological response of glioblastoma multiforme cell lines to erlotinib.

Background: Erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, exerts highly variable antiproliferative effects on human glioblastoma multiforme (GBM) cells in vitro and in vivo. As these effects are independent of EGFR baseline expression levels, more complex genetic signatures may form the molecular basis of the erlotinib-sensitive and erlotinib-resistant GBM phenotypes. The aim of the current study was to determine which genes within the EGFR signaling pathway are candidates for mediating the cellular response of human GBM towards erlotinib.

Uniform MDM2 overexpression in a panel of glioblastoma multiforme cell lines with divergent EGFR and p53 expression status.

Background: Overexpression and deletion mutation of the epidermal growth factor receptor (EGFR) gene, as well as murine double minute 2 (MDM2) overexpression have been linked to the absence of p53 gene mutations in human glioblastoma multiforme (GBM).

Materials And Methods: EGFR and MDM2 messenger (m)RNA expression profiles and p53 status were examined by reverse transcription-polymerase chain rection (RT-PCR) and gene sequencing, respectively, in a set of human wild-type (wt) p53 GBM cell lines (U-87MG, U-87MG.wtEGFR and U-87MG.

Epidermal growth factor receptor inhibition for the treatment of glioblastoma multiforme and other malignant brain tumours.

Gliomas are the most common primary central nervous system tumours and about 55% are glioblastoma multiforme (GBM). Between 40% and 50% of GBM have dysregulated epidermal growth factor receptor (HER1/EGFR), and almost half of these co-express the mutant receptor subtype EGFRvIII, which may contribute to the aggressive and refractory course of GBM. Limited therapeutic options exist for GBM, and recurrence is common.

The value of reoperative procedures after unusual reconstructions in the gastrointestinal tract associated with substantial morbidity.

Reconstructive procedures of the gastrointestinal tract after resection or for bypass surgery are well established and almost completely standardized but still may cause significant morbidity. Deviations from standard reconstructive procedures have pitfalls, especially when complex reconstructions are required, and may lead to substantial morbidity. Scientific evidence for the indication to reoperate as well as the best methods to be applied is lacking and surgical experience indispensable.

Quality of life and functional long-term outcome after partial pancreatoduodenectomy: pancreatogastrostomy versus pancreatojejunostomy.

Background: To determine the effects of pancreatogastrostomy (PG) versus pancreatojejunostomy (PJ) as types of reconstruction after partial pancreatoduodenectomy on postoperative quality of life and long-term gastrointestinal morbidity, the outcomes of 104 patients (PG, n = 63; PJ, n = 41) were evaluated.

Methods: To compare the two groups, the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (QLQ-PAN 26) standard and an additional self-developed questionnaire were used. The mean time after surgery was 6.

Inverse correlation of epidermal growth factor receptor messenger RNA induction and suppression of anchorage-independent growth by OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in glioblastoma multiforme cell lines.

Object: Quantitative and qualitative alterations in the epidermal growth factor receptor (EGFR) commonly occur in many cancers in humans, including malignant gliomas. The aim of the current study was to evaluate molecular and cellular effects of OSI-774, a novel EGFR tyrosine kinase inhibitor, on nine glioblastoma multiforme (GBM) cell lines.

Methods: The effects of OSI-774 on expression of EGFR messenger (m)RNA and protein, proliferation, anchorage-independent growth, and apoptosis were examined using semiquantitative reverse transcription-polymerase chain reaction, immunocytochemical analysis, Coulter counting, soft agar cloning, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling/fluorescence-activated cell sorting, respectively.

EGFR but not PDGFR-beta expression correlates to the antiproliferative effect of growth factor withdrawal in glioblastoma multiforme cell lines.

Background: The aim of the current study was to investigate a putative relationship between (i) growth characteristics (proliferation and tumorigenicity) of nine glioblastoma multiforme (GBM) cell lines under different growth-stimulating conditions in vitro and (ii) their basal expression of a panel of growth factor receptors/autocrine cytokines.

Materials And Methods: Basal expressions of the epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor-beta (PDGFR-beta), platelet-derived growth factor-AA (PDGF-AA) and PDGF-BB, tumor growth factor-alpha (TGF-alpha) and TGF-beta as well as tumor necrosis factor-alpha (TNF-alpha) were determined by immunocytochemistry at standard cell culture conditions (10% fetal calf serum [FCS]). Proliferation and tumorigenicity at 10% FCS and relative serum starvation (0.