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Biomedical subjects

Raimund Firsching

Publications and source records attributed to Raimund Firsching.

11 recordsLinked to original sources
PubMed2006

Increased concentrations of transforming growth factor beta1 and beta2 in the plasma of patients with glioblastoma.

Recently, several in vitro studies have demonstrated production of the potent immunosuppressive cytokine transforming growth factor beta (TGF-beta)2 in glioblastoma cell lines. Systematic studies of the concentration of TGF-beta isoforms in the plasma of patients harboring intracerebral tumors do not exist. In the present study, the concentrations of TGF-beta1 and TGF-beta2 in platelet-poor plasma of 21 patients with glioblastoma before and after extensive resection were measured by specific ELISA systems and related to survival. The plasma concentrations of latent TGF-beta1 of patients with glioblastoma prior to surgery were significantly higher in comparison to healthy control probands, but not to patients with multiple sclerosis (MS). Furthermore, latent TGF-beta2 was found to be significantly increased in the plasma of patients with glioblastoma in comparison to healthy control probands and patients with MS. After extensive resection of the tumor, the value of latent TGF-beta2 evidently decreased. Interestingly, the concentration of latent TGF-beta2 prior to surgery was correlated with survival and a strong relationship was found between the survival and the difference of latent TGF-beta2 levels prior to surgery minus the TGF-beta2 concentrations 7 days after surgery. A higher difference in these plasma concentrations >6 ng/ml vs. <6 ng/ml clearly correlates with a longer survival time. In conclusion, this study suggests that glioblastoma does secret TGF-beta2 in vivo and that TGF-beta2 may play an important role in glioblastoma patients.

Adult↗
PubMed2005

Analysis of a single nucleotide polymorphism in codon 388 of the FGFR4 gene in malignant gliomas.

The FGFR4 codon 388 polymorphism (Arg(388), Arg/Gly(388) or Gly(388)) was determined in glioblastoma multiforme (GBM), anaplastic astrocytomas (AA), diffuse astrocytomas (DA), and control muscles. Arg(388) was rare in AA, GBM, muscles, and was absent in DA. The Arg/Gly(388) and the Gly(388) frequency was equal among GBM and controls. FGFR4 expression was not related to codon 388 in GBM, and no survival differences between Arg/Gly(388) and Gly(388) tumors were found. U87 cells (Arg/Gly(388)) did not show higher invasion than U138 cells (Gly(388)). This suggests that the FGFR4 codon 388 status does not play a major role in malignant gliomas.

Base Sequence↗
PubMed2005

Different activation of mitogen-activated protein kinase and Akt signaling is associated with aggressive phenotype of human meningiomas.

PURPOSE: Activation of intracellular signaling cascades has been implicated in the growth control of benign meningiomas, but their role for meningioma progression and outcome is unknown. Here we determined the expression and function of proteins involved in mitogen-activated protein kinase (MAPK) and phosphinositol-3 kinase (PI3K)/Akt signaling in benign, atypical, and malignant meningiomas and studied their association with clinicopathologic data including meningioma recurrence. EXPERIMENTAL DESIGN: Expression of various MAPK and PI3K signaling proteins was determined in 70 primary meningiomas and, if present, in recurrent tumors by immunohistochemistry and Western blotting. The expression patterns in primary and recurrent tumors were related to clinical data. The effect of MAPK and PI3K pathway inhibition on cell proliferation and apoptosis was determined using a primary malignant meningioma cell culture. RESULTS: Atypical and malignant meningiomas showed higher levels of phospho-Akt compared with benign tumors, and their proliferation could be inhibited by PI3K blocking using wortmannin. PI3K inhibition did not induce apoptosis in malignant meningioma cells. In contrast, expression of phospho-Raf and phospho-MAPK was decreased in aggressive meningiomas compared with benign tumors, but MAPK inhibition by PD98059 resulted in tumor cell apoptosis and decreased proliferation. Reduced MAPK activation was associated with meningioma recurrence, and PI3K activation was associated with poor preclinical condition and brain invasion of malignant meningiomas. CONCLUSIONS: Both MAPK and PI3K/Akt pathways are activated at different levels in benign and malignant meningiomas. Activation of PI3K/Akt signaling contributes to the aggressive behavior of malignant meningiomas, whereas MAPK activation is involved in both proliferation and apoptosis of malignant meningiomas.

Aged↗
PubMed2005

Assessment of tumor cell invasion factors in gliomatosis cerebri.

Gliomatosis cerebri (GC) is a rare brain tumor characterized by widespread infiltration of large parts of the brain and sometimes even the spinal cord. To determine the cause of this extraordinary degree of brain invasion, we studied immunoexpression of factors associated with brain infiltration in low-grade and high-grade tumor samples from nine GC cases. We further determined the allelic status of the fibroblastic growth factor receptor 4 (FGFR4) gene at position 388 (arginine [Arg(388)] or glycine [Gly(388)]) in eighteen GC patients, because the presence of at least one Arg(388) allele has been suggested to favor tumor cell motility compared to tumor cells homozygeous for the Gly(388) allele. Immunohistochemical analyses showed that tumor samples from three GC cases expressed Tenascin-C, whereas six cases had CD44 - immunopositive tumor samples. Expression of MMP-9 was not observed in any of the nine GC patients. FGFR4 genotyping revealed the presence of the Arg(388) in 72% of the eighteen GC cases, a frequency similar to the one found in 21 common astrocytomas (71%). In tumor-free control DNA, the Arg(388) phenotype was present in 60%. These data indicate that CD44 expression might be related to the tumor infiltration in GC, and that patients suffering from GC or other common astrocytomas do not have a significantly increased frequency of the tumor cell motility-favoring Arg(388) FGFR4 allele.

Adolescent↗
PubMed2005

Expression and function of somatostatin receptors in peripheral nerve sheath tumors.

Although somatostatin receptors have been detected in many normal and neoplastic tissues, little is known of their expression and function in peripheral nerve tumors. In the present study, we examined the expression of all 5 somatostatin receptor subtypes (sst1-5) in 3 normal peripheral nerves, 3 traumatic neuromas, 27 schwannomas, 18 neurofibromas, and 177 malignant peripheral nerve sheath tumors (MPNSTs) by immunohistochemistry as well as by Western blot and reverse transcriptase-polymerase chain reaction investigations in 2 normal peripheral nerves, one neurofibroma, 5 schwannomas, and 5 MPNSTs. Immunoreactive somatostatin receptors were not detectable in normal peripheral nerve and in nonneoplastic Schwann cell proliferations. In contrast, sst2A mRNA and protein was present in 89% of schwannomas. This receptor subtype was less frequently detected in neurofibromas (22%) and MPNSTs (15%). Interestingly, sst4 was seen in 32% of MPNSTs and was almost exclusively expressed in this malignant tumor type. In support of a role in Schwann cell tumor growth control by somatostatin was the observation of induced internalization of sst2A and inhibition of cell proliferation in an NF1-associated MPNST cell line. Moreover, administration of an sst2A-selective agonist resulted in induction of MPNST cell apoptosis. We conclude that peripheral nerve sheath tumors often express at least one functional somatostatin receptor. Furthermore, our findings suggest a potential clinical role for somatostatin receptor agonists in tumor imaging and/or treatment of schwannomas and MPNSTs.

Animals↗
PubMed2004

Differential expression of sst1, sst2A, and sst3 somatostatin receptor proteins in low-grade and high-grade astrocytomas.

We have previously reported that sst2A somatostatin receptors are frequently overexpressed in human meningiomas. Initial clinical observations suggest that somatostatin analogues may also be of value for imaging and treatment of other human intracranial tumors, including astrocytomas. However, contradictory results have been reported regarding the expression of somatostatin receptors in low-grade and high-grade astrocytomas. Therefore, we determined the precise pattern of somatostatin receptor protein expression in 8 diffuse astrocytoma (DA), 10 anaplastic astrocytomas (AA), and 32 glioblastoma multiforme (GBM) using immunohistochemistry and Western blot analysis. sst1 and sst2A somatostatin receptors were not present in DA and only occasionally detected in AA. In GBM, sst1 was present in 66%, and sst2A was found in 44% of the tumors. sst3 receptors were present in 38% of DA, 40% of AA, and 84% of GBM. Thus, loss of differentiation was significantly associated with increased expression of sst1, sst2A, and sst3 somatostatin receptors. In contrast, sst4 and sst5 receptors were found in 80% and 25% of all cases, respectively, in a manner independent of histological grade. No significant correlation was found between somatostatin receptor expression and the proliferation rate of the tumors as determined by MIB-I immunostaining. Furthermore, the presence or absence of the 5 somatostatin receptor subtypes did not significantly influence survival time in 14 GBM patients.

Astrocytoma↗
PubMed2003

Prognostic relevance of MAPK expression in glioblastoma multiforme.

The objective of this study was to determine the immunoexpression pattern of the mitogen-activated protein kinase (MAPK), and related signalling proteins [protein kinase C (PKC), phospholipase Cgamma (PLCgamma)], in glioblastoma multi-forme, and to investigate their prognostic value. Paraffin-embedded biopsy samples from 26 patients [13 patients with long-term survival (LTS; N=13; median 28 months, range 13-76 months), and, for comparison, 13 patients with short-term survival (STS; N=13; median 7 months, range 1-12 months)] were investigated for the immunoexpression of MAPK, the activated pMAPK, PKC, PLCgamma, EGFR, and PTEN. Additionally, the MIB-1 proliferation index was determined. The immunoexpression pattern were related to clinical data, including analysis of their prognostic value using the Cox-proportional hazard model. No significant differences were found between STS and LTS in terms of age, Karnofsky performance status, and treatment. Whereas EGFR expression did not differ between STS and LTS and does not influence survival, expression of MAPK and activated pMAPK was significantly correlated with survival time. The percentage of pMAPK expressing cells correlated strongly with the percentage of MIB-1 positive cells. Furthermore, survival in patients with tumors expressing PKC or PLCgamma was significantly shorter. No differences were found for PTEN expression. Our findings indicate that the MAPK pathway is correlated with proliferation in gliomas, and that patient subgroups exist, in which expression of MAPK-related signalling proteins (PKC, PLCgamma) is associated with poorer prognosis. These patient subgroups may benefit from additional chemotherapeutic agents which specifically inhibit these signalling proteins.

Adult↗
PubMed2002

Brain stem lesions after head injury.

There is little knowledge on the morphology of the brain stem in survivors of head injury, as CT fails to shown brain stem lesions, and neuropathological data is only available from autopsies. As magnetic resonance imaging (MRI) sheds new light on morphological lesions of the brain, the authors investigated 100 patients with a severe head injury. MRI was performed in a prospective study within the first seven days after head injury while the patients were still in coma and on ventilation. Relating the location of the lesions as depicted by MRI with the initial CT scan and outcome, death appeared to be closely linked to the phenomenon of bilateral pontine lesions. The extent of supratentorial lesions had no bearing on survival at all in the absence of brain stem lesions. Altogether the brain stem was affected in 52%. Obviously the occurrence of bilateral upper pontine lesions is of highest predictive value for a fatal outcome. Severe destruction of supratentorial white matter as demonstrated by MRI is not related to increased mortality, as long as the brain stem is spared.

Adolescent↗
PubMed2002

Electromagnetic field hazards involving adjustable shunt valves in hydrocephalus.

OBJECT: Standard therapy for hydrocephalus involves shunts and valves, which are frequently adjustable. Because of increasing "electromagnetic smog" (for example, that generated by cellular phones), these valves are often exposed to electromagnetic fields. METHODS: Various magnetic fields were tested for their effects on two different kinds of adjustable valves. The minimum magnetic flux density affecting the adjustment of the valve was determined. Results were compared with magnetic fields found in contemporary everyday life. In homogeneous magnetic fields the adjustment of one valve (Sophysa model SM8) was changed at 5 mT, whereas the second valve (Codman Hakim model CM) was not affected. In nonhomogeneous fields the SM8 valve was affected at 25 mT and the CM valve at 15 mT. Thus, these valves may be affected by headphones and telephone receivers. Surroundings such as the Japanese magnetic suspension railway and the lead cabin of electrical railway engines, in which critical levels of magnetic flux may be present, may also affect adjustable valves. The high-frequency fields of cellular phones, however, have no effect on these valves. CONCLUSIONS: Every surgeon who implants these valves and every patient who receives them should know the possible hazards. The valve selection should be adapted to the environment of the patient. Devices with critical levels of electromagnetic flux that are used in the homes of patients should be replaced by ones with lower magnetic fields. The future construction of these valves should be modified in such a way that their adjustment requires a higher magnetic flux density, so that the valves become less sensitive to unwanted effects from environmental magnetic fields.

Cerebrospinal Fluid Shunts↗