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Jörg-Christian Tonn

Publications and source records attributed to Jörg-Christian Tonn.

13 recordsLinked to original sources
PubMed2006

Vascular endothelial growth factor A contributes to glioma-induced migration of human marrow stromal cells (hMSC).

OBJECTIVE: It has been demonstrated that murine neural stem cells (mNSCs) and human mesenchymal stroma cells migrate toward experimental gliomas, making stem cells a candidate for cellular carrier systems of anti-glioma therapy. However, few data are available on the factors involved in regulating stem cell migration. The aim of our study was to characterize the migratory and invasive behavior of adult human marrow stromal cells (hMSC) that interact with glioma cells, especially focusing on vascular endothelial growth factor A (VEGF-A)-mediated effects. METHODS: Human MSC were isolated from bone marrow biopsies carried out for hematological indications. The chemokinetic activity of hMSC in response to glioma-conditioned medium as well as VEGF-A was analyzed using a modified Boyden chamber assay. Invasion of hMSC and glioma spheroids was investigated using confrontational cultures. To provide analogous data from a well-described system, invasion of murine C17.2 neural stem cells was assessed. VEGF-A secretion by gliomas and the expression of VEGF-receptor 2 in hMSC were evaluated. RESULTS: Human MSC showed an extensive invasion into glioma spheroids. Glioma-conditioned medium significantly increased hMSC migration and also invasion, driven by chemotaxis. VEGF-A also showed significant pro-migratory and pro-invasive effects on hMSC, but in a reduced fashion compared to glioma-conditioned medium. CONCLUSIONS: Human MSC show intensive migratory and invasive behavior in the presence of glioma cells and glioma-conditioned medium. Among others, VEGF-A seems to be one important factor in enhancing and directing stem cell motility.

Animals↗
PubMed2006

Microsurgical anatomy of the lateral mesencephalic vein and its meaning for the deep venous outflow of the brain.

The cerebral venous outflow consists of the superficial system and the deep draining system. The deep one drains the areas of the great vein of Galen, the two basal veins of Rosenthal, and their tributaries. Simultaneous obstruction of these veins can effect great harm. In the case of obstruction of the vein of Galen, the basal vein can ensure the venous outflow. Therefore, attention should be paid to anastomoses between the basal vein and the infratentorial venous system. The lateral mesencephalic vein (LMV) is the most important anastomosis between the supra- and infratentorial system linking the basal vein to the superior petrosal sinus. Since microanatomical studies concerning this vein have received less attention the aim of the present study was to visualize the course of this vein, its junction with the basal vein, its tributaries and its relationship with neural structures. Fifty-two cadaveric hemispheres were examined under the operating microscope. The LMV could be identified in all cases, with a mean diameter of 1.07 mm. Thorough understanding of the microanatomy of the LMV is crucial to avoid brain damage due to venous infarction during surgery, and its preservation could ensure deep venous outflow in the case of obstruction of the vein of Galen.

Brain↗
PubMed2005

Treatment of brain metastases in renal cell carcinoma: radiotherapy, radiosurgery, or surgery?

Metastases from renal cell carcinoma raise specific therapeutic problems because they are relatively unresponsive to whole brain radiation therapy and tend to bleed. Recently, stereotactically guided high-precision irradiation as a single dose application (radiosurgery) showed promising treatment results for selected patients with brain metastases from renal cell carcinoma. Radiosurgery appears attractive due to its low risk and minimal invasiveness. Multiple lesions can be treated at the same time and retreatments can be performed for local or distant recurrences.

Brain Neoplasms↗
PubMed2005

Positron emission tomography with O-(2-[18F]fluoroethyl)-l-tyrosine versus magnetic resonance imaging in the diagnosis of recurrent gliomas.

OBJECTIVE: New treatment modalities are available for patients with glioma, which may lead to unspecific changes in posttherapeutic magnetic resonance imaging (MRI) findings. Differentiation between tumor- and therapy-associated contrast enhancement on MRI scans after treatment may be difficult. The aim of this study was to analyze the diagnostic value of O-(2-[F]fluoroethyl)-l-tyrosine (FET)-positron emission tomography (PET) and MRI in the detection of tumor recurrence in patients with glioma after radiotherapy, radiosurgery, or multimodal treatment. METHODS: The study included 36 patients with gliomas and neuroradiological diagnosis of tumor recurrence and 9 patients who had undergone radioimmunotherapy. Patients were consecutively treated between September 2001 and May 2003. A contemporary FET-PET investigation was performed in all patients. A tissue diagnosis was made for comparative analysis in all patients with progressive neuroradiological or clinical findings (32 of 45 patients). In patients with transient neuroradiological or clinical deterioration (13 of 45 patients), clinical follow-up was used to support or contradict the imaging-based diagnosis. RESULTS: Tumor recurrence was documented in 31 of 45 patients, and 14 of 45 patients were tumor free. FET-PET and MRI revealed a correct diagnosis in 44 and 36 patients, respectively. The difference was statistically significant (P < 0.01). Concordant findings after MRI and FET-PET were documented in 37 patients and discordant findings in 8 patients. The difference was statistically significant (P < 0.01). Specificity of FET-PET was 92.9%, and sensitivity was 100% (in patients suspected of having recurrent tumor as revealed by MRI). Sensitivity of MRI was 93.5%, and specificity was 50% (P < 0.05). CONCLUSION: For patients with gliomas undergoing multimodal treatment or various forms of irradiation, conventional follow-up with MRI is insufficient to distinguish between benign side effects of therapy and tumor recurrence. FET-PET is a powerful tool to improve the differential diagnosis in these patients.

Adult↗
PubMed2005

Outpatient gamma knife surgery for vestibular schwannoma: definition of the therapeutic profile based on a 10-year experience.

OBJECT: The purpose of the study was to define the therapeutic profile of outpatient gamma knife surgery (GKS) for vestibular schwannoma (VS) by using sequential tumor volumetry to quantify changes following treatment. METHODS: A total of 111 patients met the inclusion criteria. The median follow-up duration was 7 years (range 5-9.6 years). Thirty-seven patients (33%) had undergone surgery before GKS and 10 (9%) had neurofibromatosis Type 2 (NF2). The median VS volume was 1.6 cm3 (range 0.08-8.7 cm3). The actuarial 6-year tumor control rate after a single GKS treatment was 95%. Tumor swelling was observed in 43 patients (38.7%). Recurrence was significantly associated with NF2 (p < 0.003) and the reduced dose (p < 0.03) delivered to these tumors. The incidence of facial nerve neuropathy was mainly determined by surgery prior to GKS (p < 0.0001). Facial nerve radiation toxicity was mild and transient. No permanent facial nerve toxicity was observed. Trigeminal neuropathy occurred in 13 patients, and this was correlated with the VS volume (p < 0.02). The median hearing loss was -10 dB (range + 20 dB to -70 dB). The risk of hearing loss was correlated with age and transient tumor swelling (p < 0.05) but not with dose parameters or NF2. CONCLUSIONS: Outpatient GKS is feasible, effective, and safe. Its therapeutic profile compares favorably with that of microsurgery.

Ambulatory Care↗
PubMed2004

Distribution of labelled anti-tenascin antibodies and fragments after injection into intact or partly resected C6-gliomas in rats.

INTRODUCTION: For treatment of malignant glioma, radioimmunotherapy has become a valuable alternative for more than 2 decades. Surprisingly, very little is known about the distribution of intralesionally administered labelled antibodies or fragments. We investigated the migration of labelled antibodies and antibody fragments injected into intact and partly resected C6-glioma in rats at different times after injection. MATERIALS AND METHODS: Nine days after induction of a C6-glioma, 5 microl of 125I-labelled murine anti-tenascin antibodies (n = 31) or 125I-labelled fragments of anti-tenascin antibodies (n = 32) was injected slowly into the tumour (group I). In group II the tumour was subtotally resected 9 days after induction of the C6-glioma, and 24 h later the labelled antibodies (n = 30) or fragments (n = 12) were injected into the resection cavity. At 6, 24 or 48 h after the injection, animals were sacrificed, and brains removed. Distribution of labelled antibodies and fragments was determined by superimposing autoradiographs onto frozen sections and HE-stained neighbouring sections using a digital image analysing system. RESULTS: After injection into intact C6-glioma, labelled antibodies covered a maximum distance of 3.2 +/- 1.0, 4.1 +/- 1.9 and 4.8 +/- 0.9 mm after 6, 24 and 48 h, respectively; while labelled fragments were found at a distance of 6.7 mm (+/-1.1) after 24 h and 5.8 mm (+/-0.9) after 48 h (significant in univariate analysis). Following partial tumour resection, the respective distances at 24 h were 3 +/- 0.4 mm for anti-tenascin antibodies and 3.4 +/- 0.3 mm for Fab fragments. CONCLUSION: After injection into C6-glioma, labelled fragments are able to cover a greater distance than labelled antibodies. Injection of antibodies and fragments 1 day after tumour resection results in reduced velocity of both antibodies and fragments.

Animals↗
PubMed2004

Value of O-(2-[18F]fluoroethyl)- L-tyrosine PET for the diagnosis of recurrent glioma.

PURPOSE: The prognosis of patients with recurrent gliomas depends on reliable and early diagnosis of tumour recurrence after initial therapy. In this context, magnetic resonance imaging (MRI) and computed tomography (CT) often fail to differentiate between radiation- and tumour-induced contrast enhancement. Furthermore, absence of contrast enhancement, or even of 18F-fluorodeoxyglucose uptake in PET, does not exclude recurrence. The aim of this study was to establish the diagnostic value of O-(2-[18F]fluoroethyl)- L-tyrosine (FET) PET in recurrent gliomas. METHODS: Fifty-three patients with glioma (primary grading: 27=WHO grade IV, 16=grade III, 9=grade II, 1=grade I) and clinically suspected recurrence underwent FET PET scans 4-180 months after different treatment modalities. For semiquantitative evaluation, maximal SUV (SUVmax) and mean SUV within 80% and 70% isocontour thresholds (SUV80/SUV70) were evaluated and the respective ratios to the background (BG) were calculated. PET results were correlated with MRI/CT, clinical follow-up or biopsy findings. RESULTS: All patients presented with FET uptake, of varying intensity, in the area of the primary tumour after initial therapy. In the 42 patients with confirmed recurrence, there was additional distinct focal FET uptake with significantly higher values compared with those in the 11 patients without clinical signs of recurrence and showing only low and homogeneous FET uptake at the margins of the resection cavity. With respect to tumour grading, there was a slight but non-significant increase from WHO II (SUVmax/BG: 2.53+/-0.28) to WHO III (SUVmax/BG: 2.84+/-0.49) and WHO IV (SUVmax/BG: 3.55+/-1.07) recurrence. CONCLUSION: FET PET reliably distinguishes between post-therapeutic benign lesions and tumour recurrence after initial treatment of low- and high-grade gliomas.

Brain Neoplasms↗
PubMed2004

Stereotactic radiosurgery for multiple brain metastases from breast carcinoma.

BACKGROUND: The current study analyzed the feasibility and outcome of stereotactic radiosurgery (SRS) for treatment of brain metastases from breast carcinoma. METHODS: During an 8-year period, 151 patients with a combined total of 620 brain metastases from breast carcinoma underwent 197 outpatient SRS procedures. Sixty-three percent of all patients had multiple brain metastases. The median tumor volume was 2.2 cm(3) (range, 0.1-20.9 cm(3)). The mean prescribed tumor dose was 19 +/- 4 grays. Local/distant tumor recurrences were treated with additional radiosurgical therapy for patients with stable systemic disease. All patients were categorized according to the Radiation Therapy Oncology Group classification. Survival time and freedom from local tumor recurrence were analyzed using the Kaplan-Meier method. Prognostic factors were identified using the Cox proportional hazards model. RESULTS: The overall median survival duration was 10 months after SRS. Ninety-four percent of patients did not experience local brain tumor recurrence after radiosurgery. In addition, 70.2% of patients did not have disease recurrence in the brain. Most patients died of systemically progressing malignancy. A Karnofsky performance score > 70 and recursive partitioning analysis Class I were related to prolonged survival in the univariate and multivariate analyses. Age, whole-brain radiotherapy, surgery, number of metastases, chemotherapy, and latency period from diagnosis of the primary tumor to the development of brain metastases did not reach prognostic relevance in the multivariate model. Patients with RPA I, II, and III survived 34.9, 9.1, and 7.9 months, respectively. There was no treatment related permanent morbidity and mortality. The transient morbidity rate was 17%. Sixteen patients exhibited symptomatic transient complications related to treatment. CONCLUSIONS: The results of the current study indicate that SRS is a feasible treatment concept for selected patients with multiple brain metastases from breast carcinoma.

Adult↗
PubMed2004

Models for angiogenesis in gliomas.

During the last decades a lot of attention has been focussed on mechanisms of glioma vascularization, particularly in terms of investigating vascular growth factors and receptors. Recently, these efforts resulted in various approaches for antiangiogenic treatment strategies using in vitro cell culture systems as well as experimental orthotopic and non-orthotopic brain tumors. These basic science and preclinical trials need an assortment of models, which should allow investigating a variety of questions. Several objectives concerning basic endothelial cell (EC) characteristics can adequately be studied in vitro using EC monolayer assays. Three-dimensional spheroid techniques respect the more complex cell-cell and cell-environment interplay within a 3-dimensional culture. Recent advances in molecular genetic techniques offer a wide access to the genome of EC. Using these micro array or chip methods differences between micro- and macromolecular EC as well as variations within the gene pool of different organ specific EC can be assessed. To optimize the imitation of the crucial interaction of human gliomas with host endothelial cells, immunological cells and extracellular matrix, animal models are mandatory. An essential rule is to utilize an orthotopic model, since tumor-host-interaction is organ specific. To avoid alloimmunogenic responses, it is desirable to use weak or non-immunogenic glioma grafts, which is best accomplished in a syngeneic model. However, since rat gliomas poorly resemble human glioma growth patterns, human glioma xenografting into immunocompromized animals should be considered. In vivo-monitoring techniques like videoscopy via a cranial window or magnetic resonance imaging (MRI) allow for functional studies and improve the validity of the model employed. Finally, it is essentially to recognize the limitations of each model considered and to select that model which seems to be most appropriate for the objectives to be investigated.

Animals↗
PubMed2004

PTK787/ZK222584, an inhibitor of vascular endothelial growth factor receptor tyrosine kinases, decreases glioma growth and vascularization.

OBJECTIVE: The aim of this study was to test the efficacy of PTK787/ZK222584, an inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, on VEGF-dependent glioma vascularization and growth. METHODS: C6 rat glioma cells were transfected with VEGF(164) in a sense (V(+)) or antisense (V(-)) direction. Spheroids generated from V(+) or V(-) cells were implanted orthotopically into 60 rat brains. Expression of VEGF and fetal liver kinase-1 (VEGF receptor 2) was assessed immunohistochemically. Animals with V(+) gliomas received orally administered PTK787/ZK222584 on postoperative Day (POD) 1 to 12 or POD 7 to 12. Untreated animals served as negative controls, and animals with V(-) gliomas served as positive controls. Growth and vascularization were evaluated by magnetic resonance imaging and immunohistochemistry. RESULTS: Flk-1 expression was positive within tumor vessels in V(+) gliomas, whereas all C6 clones were negative for fetal liver kinase-1 in vitro. Early (POD 1-12) and delayed (POD 7-12) application of PTK787/ZK222584 in V(+) glioma-bearing animals resulted in a significant reduction of tumor size (71% and 36%, P < 0.05) as measured by magnetic resonance imaging volumetry. Early treated V(+) gliomas reached similar volumes compared with V(-) gliomas. Vessel density was significantly reduced (42.3% and 25.7%, P < 0.05), and areas of intratumoral necrosis were enlarged (by 1.7-fold after early treatment). Additionally, proliferation was decreased by 89% and 72% (P < 0.05). There was no growth-inhibiting effect of PTK787/ZK222584 on V(-) cells observed. CONCLUSION: PTK787/ZK222584 significantly halted VEGF-mediated glioma growth by inhibition of neovascularization and proliferation, providing a promising new tool in malignant glioma therapy.

Angiogenesis Inhibitors↗
PubMed2004

Safety and efficacy of outpatient gamma knife radiosurgery for multiple cerebral metastases.

This review highlights the experience of a single institution using the Leksell gamma knife for 8 years. More than 500 patients with multiple cerebral metastases received outpatient radiosurgery. The results prove that there is a high efficacy and attractively low morbidity of modern outpatient radiosurgery. When compared with whole brain radiation therapy, radiosurgery improved survival in patients with cerebral metastases. Most importantly, the number of brain metastases had no prognostic impact in patients with non-small cell lung cancer, renal cell cancer, malignant melanoma and gastrointestinal cancer.

Ambulatory Care↗