Biomedical subjects

M A Grotzer

Publications and source records attributed to M A Grotzer.

22 records · Page 2Linked to original sources

PubMed2000

Autocrine secreted insulin-like growth factor-I stimulates MAP kinase-dependent mitogenic effects in human primitive neuroectodermal tumor/medulloblastoma.

Primitive neuroectodermal tumors/medulloblastoma (PNET/MB) have similarities to neuroectodermal progenitor cells of the developing CNS. Since insulin-like growth factor I (IGF-I) exerts pleiotrophic effects on cells in the developing CNS, we evaluated the production, mitogenic effects and signaling pathways of IGF-I in PNET/MB cells and found that IGF-I is an autocrine growth factor in human PNET/MB cell lines tested. Stimulation of DAOY cells by IGF-I led to phosphorylation of its cognate receptor (IGF-IR) and resulted in cell proliferation. These effects of IGF-I were suppressed by IGF-IR blocking antibodies and by PD 98059, MAP kinase pathway inhibitor. The results demonstrate the existence of an autocrine IGF-I/IGF-IR loop and indicate that IGF-I promotes proliferation via MAP kinase pathway.

Cell Division↗

PubMedDate not supplied

Neurotrophin receptor TrkC predicts good clinical outcome in medulloblastoma and other primitive neuroectodermal brain tumors.

BACKGROUND: Neurotrophins and their cognate receptors TrkA, TrkB and TrkC regulate proliferation, differentiation and death of neuronal progenitor cells and may be implicated in the progression of medulloblastoma and other primitive neuroectodermal brain tumors (PNET). These common childhood brain tumors are composed of morphologically undifferentiated cells that have important similarities to neuroectodermal progenitor cells of the developing CNS. PATIENTS AND METHODS: To identify biologic prognostic factors in childhood PNET we determined expression levels of TrkC mRNA in tumor samples from 87 PNET patients by in situ hybridization. Comparison of TrkC mRNA expression levels with clinical variables was performed using univariate and multivariable Cox regression analysis. RESULTS: Cox regression analysis revealed that children with tumors expressing no or little TrkC mRNA had a 4.8-fold (p < 0.00005) greater risk of death than children with tumors with high TrkC mRNA expression. This hazard ratio remained consistent after adjusting for clinical variables. Five-year survival was 89% for patients with PNETs expressing high levels of TrkC mRNA and 47% for patients with PNETs expressing little or no levels of TrkC mRNA (log rank; p < 0.00005). CONCLUSIONS: The TrkC neurotrophin receptor appears to be a powerful independent prognostic factor in PNET and may have a role in patient assignment to risk-based treatment strategies.

Adolescent↗

PubMedDate not supplied

[Expression of the neurotrophin-receptor TrkB predicts outcome in nephroblastomas: results of a pilot-study].

BACKGROUND: The neurotrophin-receptor TrkB plays an important role in pathogenesis, biology and prognosis of neuroblastoma. Expression of TrkB on aggressive neuroblastomas leads to proliferation and survival of the tumor cells and is associated with an unfavorable prognosis. It is now known that Trk receptors are also expressed in extraneural tissues including the kidney. PATIENTS AND METHODS: To study the role of the neurotrophin-receptor TrkB in nephroblastoma/Wilms' Tumor (WT), we determined TrkB mRNA expression by semiquantitative duplex RT-PCR in 39 primary WT. Comparison of mRNA expression levels with clinical variables was performed using Cox regression analysis. RESULTS: The 5-year overall survival was significantly worse for patients with tumors expressing high levels of a functional TrkB-receptor (TrkBfull) in comparison to patients with low levels of TrkBfull (70 % versus 100 %, p=0.005). Conversely, children with tumors expressing high mRNA levels of a functionally inactive truncated TrkB receptor (TrkBtrunc) had a significantly higher 5-year overall survival rate in comparison to patients with low levels of TrkBtrunc (100 % versus 68 %, p=0.003). The hazard ratios for TrkBfull and TrkBtrunc remained significant after adjusting for tumor stage. All WT with high levels of TrkB also expressed the ligand brain-derived neurotrophic factor (BDNF). CONCLUSIONS: Full-length and truncated TrkB appear to be important prognostic factors in WT. Their expression should be assessed prospectively in a larger panel of WT and may have a future role in patient assignment to risk-based treatment strategies. TrkB signaling may be reduced in WT with favorable outcome due to low numbers of TrkB receptors or a competitive effect of functionally inactive TrkBtrunc.

Adolescent↗

PubMedDate not supplied

Paediatric medulloblastoma cells are susceptible to Viscum album (Mistletoe) preparations.

BACKGROUND: Medulloblastoma constitute more than 20% of all paediatric brain tumours and are the most common malignant brain tumours in children. Adjuvant chemotherapy has seen a strong increase in the use of complementary medicine for cancer treatment. Evidence for cytotoxic and apoptotic effects of Viscum album (Mistletoe) in vitro is available, however, no data concerning paediatric tumours, especially paediatric brain tumours, has been provided so far. MATERIALS AND METHODS: In order to compare the receptiveness of medulloblastoma cells to different Viscum album preparations, in vitro cytotoxic effects of eight Viscum album extracts on four different paediatric medulloblastoma cell lines were analysed by MTT-Tests. Lectin contents of the extracts were determined to correlate them with the mitochondrial activity of mistletoe-treated cells. Flowcytometric analyses with Annexin V-FITC staining were carried out to quantify the amount of apoptotic cells compared to necrotic and viable cells. RESULTS: Data obtained with the medulloblastoma cell lines, Daoy, D342, D425 and UW-288-2, treated with Viscum album preparations from eight dissimilar host trees (Iscucin Abietis, Pini, Populi, Mali, Salicis, Crataegi, Quercus and Tiliae), indicated a significant growth-inhibition of all cell lines, yet the cell susceptibility was dissimilar against the different extracts. The decrease in mitochondrial activity and increase in apoptosis correlated with the lectin content of the used preparation in a dose-dependent manner. CONCLUSION: These in vitro results show that paediatric medulloblastoma cells respond to Viscum album preparations, by undergoing cell death through apoptosis and that this growth-inhibition correlates with the lectin content of the used preparation.

Annexin A5↗