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K Rössler

Publications and source records attributed to K Rössler.

18 recordsLinked to original sources
PubMed2006

Immunohistochemical analysis of platelet-derived growth factor receptor-alpha, -beta, c-kit, c-abl, and arg proteins in glioblastoma: possible implications for patient selection for imatinib mesylate therapy.

Inhibition of tyrosine kinase (TK) receptors by synthetic small molecules has become a promising new therapy option in oncology. The TK inhibitor imatinib mesylate selectively targets PDGFR-alpha, -beta, c-kit, c-abl and arg and has proven successful in the treatment of chronic myeloid leukaemia. In recurrent glioblastoma, phase II therapy trials using imatinib mesylate have been initiated. As only a fraction of patients seems to benefit from imatinib mesylate therapy and due to potential side effects and high costs of imatinib mesylate therapy, selection of the right patients is important. The goal of our study was to assess systematically immunohistochemical expression of the major TKs targeted by imatinib mesylate in glioblastoma, as expression of these factors could be used to select patients for imatinib mesylate therapy. In a cohort of 101 glioblastoma patients, anti-PDGFR-alpha, -beta, c-kit, c-abl and arg protein immunohistochemistry was performed. Expression of these proteins was assessed semi-quantitatively and correlated with patient survival.PDGFR-alpha and arg expression in tumor cells was widespread in 1/101 cases, respectively. Focal PDGFR-alpha, -beta, c-kit, c-abl and arg immunolabeling was detected in 25/101, 19/101, 4/101, 7/101 and 31/101 cases, respectively. Statistical analysis did not reveal any correlation between expression of the TKs and patient survival. We show here for the first time in a large series of glioblastomas that PDGFR-alpha, -beta, c-kit, c-abl and arg expression is immunohistochemically detectable in a fraction of cases. The value of anti-tyrosine kinase immunolabeling as predictive factor for patient selection remains to be clarified by comparative analysis of tumor tissue of therapy-responders versus non-responders.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Presence of D110 antigen expressing immunocompetent cells in glioblastoma associates with prolonged survival.

Monoclonal antibody D110 has recently been described as a novel marker of hypoxic tissue damage, reacting with a so far unknown antigen with preferential expression in the central nervous system. The aim of the study was to investigate D110 immunoreactivity in glioblastoma, its association with the expression of hypoxia-related proteins and its impact on patient outcome. A total of 114 consecutive adult patients who underwent first operation of primary glioblastoma were included in this study. We evaluated D110 immunoreactivity qualitatively and semi-quantitatively and correlated it with expression of hypoxia inducible factor 1 alpha (HIF-1alpha), expression of vascular endothelial growth factor (VEGF), and with patient survival using univariate and multivariate statistical analysis. We observed D110 immunolabelling in 85.1% of the cases. D110 immunoreactivity was detectable in infiltrating HLA-DR and CD68 expressing cells, most likely microglial cells or haematogenous cells of monocyte/macrophage lineage. In the peripheral lymphoreticular system, immunohistochemistry disclosed selective D110 labelling of Langerhans cells and of dendritic cells of the thymic medulla. Univariate statistical analysis revealed significantly longer survival of patients whose glioblastomas contained D110 immunoreactive infiltrating cells. There was no association between presence of D110 immunoreactive cells and expression of HIF-1alpha and VEGF. We conclude that D110 immunoreactivity in glioblastoma does not seem to be related to tissue hypoxia. D110 identifies immunocompetent cells, which positively influence survival of glioblastoma patients.

Adult↗
PubMed2003

Survival with dacarbazine and fotemustine in newly diagnosed glioblastoma multiforme.

A total of 55 patients with histologically proven glioblastoma multiforme (total gross resection: n=24, subtotal resection: n=20, stereotactic biopsy: n=11) were treated with the combination of dacarbazine (D) (200 mg m(-2)) and fotemustine (F) (100 mg m(-2)) and concomitant radiotherapy (2 Gy day(-1), 5 days per week using limited fields up to 60 Gy) to assess efficacy and toxicity of this regimen. Survival (median survival, 12-, 18- and 24-month survival rates) and time to progression (median time to progression (TTP), 6-month progression-free survival) were analysed by Kaplan-Meier's method. A total of 268 (range 1-8, median: 5) cycles were administered. Median survival is 14.5+ (range: 0.5-40+) months, and the 12-, 18- and 24-month survival rates are 58, 29 and 23%, respectively. Median TTP from the start of D/F therapy is 9.5+ (range: 0.5-33+) months. The 6-month progression-free survival is 54%. Partial remissions were observed in 3.6%. Main toxicity was thrombocytopenia. Five patients were excluded from further D/F application, four patients because of prolonged thrombocytopenia NCI-CTC grades 3 and 4 and one patient because of whole body erythrodermia. One patient died because of septic fever during thrombocytopenia and leukopenia NCI-CTC grade 4 after the first cycle. No other toxicities of NCI-CTC grade 3 or 4 occurred. The treatment is feasible in a complete outpatient setting and the results of the D/F regimen justify further investigations with these compounds.

Adolescent↗
PubMed2002

Anatomical landmarks for image registration in frameless stereotactic neuronavigation.

OBJECTIVE: Frameless stereotactic navigation devices require preoperative application of skin markers (SM) and planning radiography, which limits their even wider use. Therefore, we prospectively studied the applicability and accuracy of anatomic "natural" markers (NM) for image registration. METHODS: The accuracy of NM was evaluated in 26 patients operated on in the supine (n=24) or sitting (n=2) position, either by comparison to our standard navigation protocol using SM and planning radiography or by the deviation of anatomic landmarks using a routine diagnostic radiograph. In 21 cases, NM were compared to SM with planning radiography (computed tomography, or CT, in nine cases and magnetic resonance imaging, or MRI, in 12). The root mean square error (RMSE) of the registered volume was calculated by the Philips EasyGuide Neuro frameless stereotactic navigation system and compared between the two registration modalities. RESULTS: The mean RMSE was 3.2 mm+/-1.0 mm standard deviation using NM vs 2.9+/-1.0 mm using self-adhesive SM (P=0.13, Student's t-test). Computed tomography was slightly more accurate than MRI planning (mean RMSE 3.2 mm vs 3.3 mm). In three cases, diagnostic radiography (MRI) was used with a mean RMSE of 5.3 mm but acceptable intraoperative landmark correlation. CONCLUSION: Our pilot study demonstrates insignificant loss of registration accuracy using NM compared to SM. Additionally, the radiologic planning investigation and accuracy loss due to SM movement may be avoided.

Adolescent↗
PubMed2002

Fibrous meningeal tumours with extensive non-calcifying collagenous whorls and glial fibrillary acidic protein expression: the whorling-sclerosing variant of meningioma.

Meningiomas comprise a wide range of morphological patterns. We describe unusual fibrous meningeal tumours in two patients, composed of extensive non-calcifying collagenous whorls of varying size, resembling non-calcified psammoma bodies, while interposed tumour cells are sparse. Immunohistochemistry showed expression of S-100, vimentin and glial fibrillary acidic protein, whereas only single tumour cells stained for epithelial membrane antigen. Electron microscopy detected desmosomes or desmosome-like structures in both specimens. We conclude that these tumours represent a peculiar whorling-sclerosing variant of fibrous meningioma. Recognition of this meningioma variant is important in the differential diagnosis of meningioma versus other fibrous tumours of the meninges, including solitary fibrous tumours of the meninges, unusual forms of desmoplastic gliomas or chondroid tumours.

Aged↗
PubMed2001

Expression of hypoxia-inducible factor-1 alpha in oligodendrogliomas: its impact on prognosis and on neoangiogenesis.

BACKGROUND: Hypoxia-inducible factor (HIF)1 alpha is considered to play a key role in the adaptation of cells to hypoxia by stimulating angiogenesis via regulation of vascular endothelial growth factor and by metabolic adaptation to O(2) deprivation. METHODS: Expression of HIF-1 alpha protein and p53 was investigated by immunohistochemistry in 51 specimens of supratentorial pure oligodendrogliomas. Microvessels density (MVD) was determined by anti-CD34 immunostaining. The influence of HIF-1 alpha expression on survival was investigated using univariate and multivariate analysis. RESULTS: Strong expression of HIF-1 alpha was observed in 12 (23.5%) specimens, moderate in 21 (41.2%) specimens, and weak in 8 (15.7%) cases, and no expression was found in 10 samples (19.6%). There was no correlation of HIF-1 alpha expression with histologic grading (P = 0.428, Mann-Whitney test). Hypoxia-inducible factor-1 alpha expression and MVD showed a strong correlation (P < 0.001, r = 0.735, Spearman coefficient of correlation). Overexpression of p53 was observed in only two cases. Patients with strong or moderate expression of HIF-1 alpha had a significantly shorter overall survival rate compared with those with low or no expression in univariate (P = 0.0434; log-rank test) and multivariate analysis (P = 0.0187). CONCLUSIONS: Overexpression of HIF-1 alpha indicates a diminished prognosis in oligodendrogliomas, independent of p53 status. This finding may be explained by the strong vascularization of these tumors that prevents hypoxia and allows O(2) diffusion and henceforth tumor progression.

Adult↗
PubMed2000

Ventricular cerebrospinal fluid and serum concentrations of sTNFR-I, IL-1ra, and IL-6 after aneurysmal subarachnoid hemorrhage.

Postsubarachnoid hemorrhage, systemic inflammatory response syndrome and associated organ system failure are more frequently found in patients in poor neurologic condition. Since subarachnoid hemorrhage causes a profound intrathecal inflammatory response with production of proinflammatory cytokines TNFalpha, IL-1beta, and IL-6, a possible explanation for this association is that brain-derived cytokines may enter the systemic circulation in the presence of postsubarachnoid hemorrhage blood brain barrier disruption to systemically activate inflammatory cascades and thereby contribute to the development of postsubarachnoid hemorrhage systemic inflammatory response syndrome and extracerebral organ system failures. In 44 patients with aneurysmal subarachnoid hemorrhage admitted within 3 days of the initial bleed, extracerebral organ system functions were assessed individually and in aggregate using the modified Multiple Organ Dysfunction Score. Serum and cerebrospinal fluid concentrations of soluble tumor necrosis factor-alpha receptor-I, interleukin-1beta receptor antagonist, and IL-6 were determined during the first 2 weeks after subarachnoid hemorrhage and tested for correlation with (1) admission Hunt-Hess grade, (2) development of systemic inflammatory response syndrome and extracerebral organ system failures, and (3) neurologic outcome. The development of postsubarachnoid hemorrhage systemic inflammatory response syndrome and extracerebral organ system failures was paralleled by a significant increase in serum but not in cerebrospinal fluid levels of soluble tumor necrosis factor-alpha receptor-I and IL-1ra, that is, patients with and without extracerebral organ system failures did not differ in pattern and time course of cerebrospinal fluid cytokine concentrations. In contrast, increasing soluble tumor necrosis factor-alpha receptor-I and interleukin-1beta receptor antagonist serum levels correlated with a higher Multiple Organ Dysfunction score and with individual organ system dysfunctions. Postsubarachnoid hemorrhage, systemic inflammatory response syndrome and extracerebral organ system failures could therefore not be linked to changes in cerebrospinal fluid cytokine concentration profiles.

Adult↗
PubMed1998

Intraoperative computed tomography guided neuronavigation: concepts, efficiency, and work flow.

Image-guided surgery is currently considered to be of undisputed value in microsurgical and endoscopical neurosurgery, but one of its major drawbacks is the degradation of accuracy during frameless stereotactic neuronavigation due to brain and/or lesion shift. A computed tomography (CT) scanner system (Philips Tomoscan M) developed for the operating room was connected to a pointer device navigation system for image-guided surgery (Philips EasyGuide system) in order to provide an integrated solution to this problem, and the advantages of this combination were evaluated in 20 cases (15 microsurgical and 5 endoscopic). The integration of the scanner into the operating room setup was successful in all procedures. The patients were positioned on a specially developed scanner table, which permitted movement to a scanning position then back to the operating position at any time during surgery. Contrast-enhanced preoperative CCTs performed following positioning and draping were of high quality in all cases, because a radiolucent head fixation technique was used. The accuracy achieved with this combination was significantly better (1.6:1.22.2). The overall concept is one of working in a closed system where everything is done in the same room, and the efficiency of this is clearly proven in different ways. The most important fact is the time saved in the overall treatment process (about 55 h for one operating room over a 6-month period). The combination of an intraoperative CCT scanner with the pointer device neuronavigation system permits not only the intraoperative control of resection of brain tumors, but also (in about 20% of cases) the identification of otherwise invisible residual tumor tissue by intraoperative update of the neuronavigation data set. Additionally, an image update solves the problem of intraoperative brain and/or tumor shifts during image-guided resection. Having the option of making an intraoperative quality check at any time leads to significantly increased efficiency, improves the operating work flow because of the closed-system concept, and offers an integrated solution for improved patient work flow and clinical outcome.

Brain Neoplasms↗
PubMed1997

Tumour blood flow and partition coefficients: correlation with grade of cerebral gliomas using xenon-enhanced computed tomography.

It is possible to underestimate the grade of nonenhancing cerebral tumours on conventional contrast-enhanced MRI or CT. Differentiation of high- and low-grade gliomas by measurement of the brain-blood partition coefficient lambda (T lambda) with Xe-enhanced CT (XeCT) has been reported. We assessed the practical applications of XeCT in suspected low-grade astrocytomas. We examined 15 patients with tumours which showed no contrast enhancement on conventional MRI and CT, using XeCT. Tumour blood flow (TBF) and T lambda were calculated. Fourteen patients underwent surgery, one patient had a biopsy. We recognized three histological groups. While T lambda differed significantly between them, TBF did not. Group 1 contained grade II-III astrocytomas and T lambda was 0.77; group 2 contained grade I-II astrocytomas with T lambda 1.14, and group 3 four oligodendrogliomas in which a T lambda of 1.50 was found.

Adolescent↗
PubMed1997

Cavernous malformations: from frame-based to frameless stereotactic localization.

An exact surgical approach to cavernous malformations, in particular those located in areas of critical brain function, is important for their microsurgical resection without putting too much strain on the patient. During a two-year period, 29 cavernoma resections were performed. Stereotactic guidance was performed in 16 cases (55.2%). Nine cavernomas located in the supratentorial region were resected using the stereotactic operating microscope "MKM", which represents 21.6% of a total of 51 MKM-navigated operations; in one further case system referencing failed. The experience gathered with this frameless stereotactic system is compared to a retrospective analysis of 5 frame-based stereotactic cavernoma localizations. Frameless stereotactic localization has been shown to be sufficiently accurate but more advantageous than frame-based techniques in terms of utility, ease of integration, and detailed image-guided anatomical information. Software improvements have resulted in a high stability of the frameless stereotactic system.

Adult↗
PubMed1997

Proliferation and DNA fragmentation in meningioma subtypes.

Atypical meningioma has been introduced as tumour subtype of intermediate biological behaviour between classical and malignant meningiomas. To substantiate this three-step scale of malignancy, we assessed the proliferative activity reflected by Ki-67 (MIB1) labelling index (LI) in a series of 89 meningiomas, including 15 classical, 29 atypical, 35 anaplastic tumours, and 10 haemangiopericytomas and papillary meningiomas. The possible correlation of proliferation with the frequency of apoptosis and their relations to BCL-2 immunoexpression was investigated in seven classical, 10 atypical and 10 malignant meningiomas. Apoptosis was demonstrated by evaluation of the frequency of apoptotic figures, by the enzymatic technique of in situ tailing (IST) which stains apoptotic DNA fragments, and by DNA preparation and gel electrophoresis demonstrating DNA laddering in frozen tissues of five meningiomas. MIB1 LI revealed a highly significant increase from classical through atypical to anaplastic meningiomas (P < 0.0001); haemangiopericytomas and papillary meningiomas were well within the range of atypical meningiomas. IST indices rose with increasing malignancy and correlated with MIB1 LI (P < 0.0001): they showed a weak inverse correlation with BCL-2 immunoexpression (P = 0.05). BCL-2 expression tended to decrease with malignancy grade and was unrelated to MIB1 LI or frequency of apoptosis. Our data show that (i) apoptosis is a feature of meningiomas, significantly correlated with the malignancy scale. (ii) DNA fragmentation shows significant correlation with proliferation and inversely with BCL-2 expression; (iii) proliferation indices and frequencies of apoptosis/DNA fragmentation within meningioma subgroups corroborate the intermediate biological position of the atypical meningioma between classical and malignant meningiomas.

Antigens, Nuclear↗
PubMed1996

Dopamine D2 receptor imaging in pituitary adenomas using iodine-123-epidepride and SPECT.

UNLABELLED: Epidepride is a novel benzamide derivative with high affinity for D2 receptors. Epidepride, in its 123I-labeled form, can be used for SPECT imaging of striatal and extrastriatal dopamine D2 receptors. The present study evaluated the usefulness of epidepride and SPECT for in vivo imaging of dopamine receptors in pituitary adenomas. METHODS: SPECT imaging was performed in 19 patients with pituitary adenomas (among them 9 patients had prolactinoma, 4 acromegaly, 4 clinically nonfunctioning pituitary adenoma, 1 Cushing's disease and 1 Nelson's syndrome) and 7 control subjects 180 min after intravenous bolus injection of 3.9 +/- 1.1 mCi [123I]epidepride. The ratio target/cerebellum minus 1, reflecting specific/ nonspecific binding was used as semiquantitative measure of D2 receptor binding. RESULTS: Eight of nine prolactinoma patients demonstrated specific binding within the adenoma. The adenoma/ cerebellum ratio 3 hr p.i. showed a wide variation with values from 2.5-33. In three prolactinomas, binding was higher than in the striatum. Specific binding within the lower range of prolactinomas (adenoma/cerebellum ratios 2 and 4.8) could be demonstrated in two of four GH-secreting adenomas. All four nonfunctioning tumors showed specific binding. The adenoma/cerebellum ratio was within the lower range of prolactinomas (5.2-7.5) in three of these patients but extremely high in one (52.3). No specific tracer uptake could be demonstrated in patients with Cushing's disease or Nelson's syndrome. The striatum/cerebellum ratio 3 hr p.i. in pituitary adenoma patients was not significantly different from control subjects (17.3 +/- 5.5 versus 17.8 +/- 6.6; patients versus control subjects). CONCLUSION: Epidepride appears to be an excellent ligand for in vivo imaging of dopamine D2 receptors in pituitary adenomas. Epidepride SPECT could serve as a predictor for response to dopamine agonist treatment.

Acromegaly↗
PubMed1995

Suprasellar meningioma with expression of glial fibrillary acidic protein: a peculiar variant.

A 24-year-old female presented with a 3-year history of a suprasellar and intraventricular solid midline process measuring about 3 x 4 cm. At surgery, this tumour was sharply delineated and of stone-like firmness and was removed completely. Histology suggested meningioma, featuring nests and cords of epithelium-like cells with prominent cytoplasm amidst abundant fibrous stroma with prominent lymphoplasmocellular infiltration. Immunocytochemically, the tumour cells expressed vimentin, S-100 protein, epithelial membrane antigen, cytokeratins, and most surprisingly, glial fibrillary acidic protein (GFAP). Ultrastructural investigation revealed abundant intermediate filaments and occasionally dense secretory granules in tumour cells with short, finger-like cytoplasmic processes joined by very rare small, but well-developed desmosomes. This tumour most likely represents a peculiar variant of meningioma with prominent production of GFAP, as previously described [Budka H (1986) Acta Neuropathol (Berl) 72: 43-54].

Adult↗
PubMed1995

[Testing methods for the characterization of catheter balloons and lumina].

The present paper reports on the characterization of catheter balloons and lumina on the basis of such known parameters as residual volume, compliance, burst pressure and flow rate, with the aim of developing standards, test methods and testing equipment as well as standards. These are becoming ever more important with the coming into force of the EC directive on medical products [7] and the law governing medical products in Germany [13], which requires manufacturers to specify the properties of their products. Our testing concept is based on a commercially available machine that subjects materials to alternating extension and compression forces over the long-term, to which we added a special hydraulic module. Using the multimedia technology we achieved a real time superimposition of the volume-diameter curve on the balloon. The function of the testing device and method is demonstrated on dilatation catheters. Our initial results reveal compatibility with the requirements of the 1% accuracy class. Use of this methodology for comparative testing of catheters and quality evaluation is recommended.

Catheterization↗
PubMed1992

Expression of leucocyte adhesion molecules at the human blood-brain barrier (BBB).

The expression of leucocyte adhesion molecules was studied on cerebral endothelia by immunocytochemistry. In peritumoral "normal" brain tissue we found low endothelial expression of ICAM1, LFA3, CD44, and CD9, whereas VLA1 was present on vessels in high incidence and density. LFA1, CD2, and CR3 were found on intraluminal and parenchymal leucocytes, but were absent on brain vessels. In brain tumors and inflammatory brain lesions, we observed an up-regulation of endothelial ICAM1 and LFA3 expression, whereas other adhesion molecules on endothelial cells remained unchanged. Within the brain parenchyma, ICAM1 and LFA3 were found on astrocytes and tumor cells; on the contrary, LFA1 was expressed on microglial cells similar to CR3. CD44 and CD9 showed a diffuse neuropil expression in normal and tumoral tissue, whereas VLA1 was not expressed on any parenchymal cells. Our data show that multiple different adhesion molecules are present on blood-brain barrier endothelium (BBB) under normal conditions and some adhesion molecules are up-regulated in brain tumors and under inflammatory conditions. The presence of adhesion molecules in the vessel walls as well as on parenchymal cells like astrocytes and microglia may guide inflammatory cells into and through the brain in the course of immune surveillance and inflammation.

Antibodies, Monoclonal↗
PubMed1991

Expression of adhesion molecules and histocompatibility antigens at the blood-brain barrier.

The migration of inflammatory cells through the blood-brain barrier in health and disease involves complex interactions between hematogenous cells, endothelial cells, the basement membrane and the perivascular glia limitans. Recent evidence is presented, suggesting that part of these interactions involve antigen independent mechanisms, mediated by cellular adhesion molecules. The accessibility of endothelial adhesion molecules in the intact blood-brain barrier is lower compared to vessels in other organs. This may account for the low traffic of hematogenous cells through the normal blood-brain barrier. However, in inflammatory conditions the expression of endothelial adhesion molecules is upregulated, which may lead to recruitment of inflammatory cells into the lesions. Antigen specific activation of T-cells at the blood-brain barrier apparently takes place mainly at perivascular monocytes and microglia cells. In severe inflammatory lesions, however, astrocytes may be additionally involved in antigen presentation.

Animals↗
PubMed1991

Inflammation in the nervous system. Basic mechanisms and immunological concepts.

The basic questions in the pathogenesis of inflammation in the nervous system are how inflammatory cells reach the brain, where they recognize their antigen, how the nervous system interacts with local immune regulation in the lesion, and how inflammatory cells induce irreversible tissue damage. These questions have been addressed by studying the pathogenesis of experimental models of encephalomyelitis. The minimal requirement to start brain inflammation is the presence of activated circulating T-cells directed against a brain antigen and of antigen presenting cells in meninges and perivascular spaces of the nervous system. Such a constellation, however, only results in the disease after hypersensitization, i.e. in the presence of very high numbers of circulating autoreactive T-cells. Other local and systemic immunological factors may profoundly lower the threshold for the induction of brain inflammation. They include antigen recognition on cells in the brain parenchyma (microglia, astroglia), local upregulation of MHC antigens and possibly adhesion molecules (by cytokines or as a consequence of brain injury) and the presence of additional humoral immune responses against brain antigens (autoantibodies). Focal production of cytokines by inflammatory cells as well as by resident cells of the brain plays an important role in determining the activity of the inflammatory process and in inducing effector cells and inflammatory mediators, responsible for tissue destruction. Whereas in pure T-cell mediated auto-immune encephalomyelitis these activated effector mechanisms have low selectivity and mainly induce a "bystander" damage of CNS tissue, additional presence of autoantibodies may focus the immune reaction to specific targets, thus inducing, in high sensitivity, very selective tissue destruction. The present experimental data suggest that different immunological pathways may finally lead to quite similar inflammatory demyelinating lesions. Thus, brain lesions in individual multiple sclerosis patients may develop on a quite diverse immunological background.

Animals↗