Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: RECEPTOR ; CELLS ; EXPRESSION ; GROWTH ; GROWTH-FACTOR ; IONIZING-RADIATION ; proliferation ; CELL ; COMBINATION ; Germany ; IN-VIVO ; KINASE ; PATHWAY ; PATHWAYS ; THERAPY ; TYROSINE KINASE ; SUPPORT ; EXPOSURE ; TISSUE ; radiation ; TISSUES ; tumour ; CONTRAST ; cell culture ; culture ; TARGET ; immunohistochemistry ; RADIATION-THERAPY ; EFFICACY ; NETHERLANDS ; SQUAMOUS-CELL CARCINOMAS ; RECEPTORS ; GLIOMAS ; PERMEABILITY FACTOR ; BRAIN-TUMORS ; TUMOR-GROWTH ; GLIOMA ; anti-angiogenic therapy,glioblastoma multiforme,radiotherapy,VEGF receptor-coexpression ; FACTOR RECEPTOR-1 ; HUMAN GLIOMAS
    Abstract: In tumour-induced angiogenesis of gliomas, vascular endothelial growth factor (VEGF) and its receptors fms-like tyrosine kinase (Flt-1) and kinase-insert-domain-containing receptor (KDR) play a major role and are promising targets for tumour therapy. Nevertheless, preliminary results of such therapies could not prove clinical efficacy and thus make a profound knowledge of VEGF regulation essential. Based on earlier results, which demonstrated an inhibitory influence of VEGF on Flt-1-expressing glioblastoma cells [1], in the present study we focused on the extent of VEGF and VEGF receptor coexpression and possible therapeutical consequences.Protein expression of VEGF, Flt-1 and KDR was analysed by immunohistochemistry in native tumour tissues of 63 glioblastomas. VEGF could be detected in all glioblastomas. Additionally and independently to the expected Flt-1 and KDR expression in tumour endothelia, we found a coexpression of VEGF with Flt-1 in tumour cells of 46 and with KDR in 45 glioblastomas. After exposure of glioblastoma cells to X-ray radiation we observed a strong dose-dependent increase of VEGF secretion in two glioblastoma cell cultures by up to 46% and 96%, respectively that originated from an increased VEGF mRNA expression. In contrast, under the same conditions secretion of HGF/SF was only slightly elevated and bFGF despite being strongly increased remained at very low overall amounts compared to VEGF. Based on previous data on an autocrine function of VEGF in Flt-1-expressing glioblastoma cells we hypothesise that the X-ray radiation induced upregulation of VEGF might result in a downregulation of tumour cell proliferation and thus lead to a reduced sensitivity to radiation therapy. Therefore our results support the idea that a combination of anti-VEGF and radiation therapy might prove a promising new option in fighting against one of the most fatal tumour types
    Type of Publication: Journal article published
    PubMed ID: 15015778
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
  • 3
    Keywords: RECEPTOR ; ANGIOGENESIS ; CELLS ; GROWTH ; GROWTH-FACTOR ; IN-VITRO ; INHIBITOR ; proliferation ; CELL ; Germany ; IN-VIVO ; INHIBITION ; KINASE ; MODEL ; THERAPY ; TYROSINE KINASE ; VITRO ; VIVO ; DRUG ; MICE ; COMPLEX ; COMPLEXES ; TYPE-1 ; TYROSINE KINASE INHIBITOR ; ALPHA ; TARGET ; MOUSE ; PATTERNS ; EFFICACY ; PLEXIFORM NEUROFIBROMAS ; TARGETS ; inflammation ; NERVE SHEATH TUMORS ; FEATURES ; ONCOLOGY ; PATTERN ; XENOGRAFTS ; IMATINIB MESYLATE ; SIZE ; KIT ; FRAGMENT ; INHIBIT ; PDGFR ; neurofibromatosis ; tumours ; Type ; RECEPTOR-TYROSINE-KINASE ; Glivec
    Abstract: Plexiform neurofibromas (PNF), one of the major features of neurofibromatosis type 1 (NF1), are characterized by complex cellular composition and mostly slow but variable growth patterns. In this study, we examined the effect of imatinib mesylate, a receptor tyrosine kinase inhibitor, on PNF-derived Schwann cells and PNF tumour growth in vitro and in vivo. In vitro, PNF-derived primary Schwann cells express platelet-derived growth factors receptors (PDGFR) alpha and beta, both targets of imatinib, and cell viability was reduced by imatinib mesylate, with 50% inhibition concentration (IC50) of 10 mu M. For in vivo studies, PNF tumour fragments xenografted onto the sciatic nerve of athymic nude mice were first characterized. The tumours persisted for at least 63 days and maintained typical characteristics of PNFs such as complex cellular composition, low proliferation rate and angiogenesis. A transient enlargement of the graft size was due to inflammation by host cells. Treatment with imatinib mesylate at a daily dose of 75 mg/kg for 4 weeks reduced the graft size by an average of 80% (n = 8), significantly different from the original sizes within the group and from sizes of the grafts in 11 untreated mice in the control group (P 〈 0.001). We demonstrated that grafting human PNF tumour fragments into nude mice provides an adequate in vivo model for drug testing. Our results provide in vivo and in vitro evidence for efficacy of imatinib mesylate for PNF
    Type of Publication: Journal article published
    PubMed ID: 19921098
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: radiotherapy ; SURVIVAL ; tumor ; Germany ; THERAPY ; FOLLOW-UP ; imaging ; SITE ; meningioma ; TUMORS ; PATIENT ; MRI ; MAGNETIC-RESONANCE ; magnetic resonance imaging ; stereotactic radiotherapy ; PROGRESSION ; PATTERNS ; HEALTH ; TUMOR PROGRESSION ; RECURRENCE ; BENIGN ; ESCALATION ; INTENSITY-MODULATED RADIOTHERAPY ; FAILURE ; RECURRENT ; ORGANIZATION ; BENIGN MENINGIOMAS ; ONCOLOGY ; PATTERN ; MENINGIOMAS ; intracranial meningioma ; long-term experience ; outcome ; TIMES ; INSTITUTION ; Follow up ; CAVERNOUS SINUS ; SKULL-BASE MENINGIOMAS
    Abstract: The aim of this work is to evaluate patterns of failure in patients with recurrent meningioma after stereotactic radiotherapy. Of 411 patients with intracranial meningioma treated with radiotherapy at our institution, 22 patients with local tumor progression diagnosed by magnetic resonance imaging (MRI) after radiotherapy (RT) were identified and further investigated. The histologic grade of the meningiomas was World Health Organization (WHO) grade I in 54.5%, WHO grade II in 27.3%, and WHO grade III in 9.1% of cases. Fourteen patients had received fractionated stereotactic RT; five patients underwent intensity-modulated RT. The median total dose was 57.6 Gy at 1.8 Gy/fraction, five times weekly. Local recurrences were divided into the dosimetric categories "central" ("in-field") and "marginal" ("out-field"). Median follow-up was 59.5 months. Eleven local failures were found to be central, and 11 were marginal. Recurrence-free survival (P 〈 0.05) and site of local recurrence (P 〈 0.05) depended statistically significantly on histology. Median recurrence-free survival was 46 months for patients with benign meningioma (WHO grade I) and 31.5 months for patients with higher-grade meningioma (WHO grade II/III). In the WHO grade I group, three recurrences were central and nine were marginal, whereas in the WHO grade II/III group seven recurrences were central and one was marginal. Median time to local tumor progression and site of local recurrence significantly depended on histological grade of meningioma. Regarding site of failure, improvement of dose coverage for benign meningiomas and dose escalation for high-grade tumors might further improve therapy outcome
    Type of Publication: Journal article published
    PubMed ID: 20012910
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Keywords: CANCER ; HEPATOCELLULAR-CARCINOMA ; GENE ; NERVOUS-SYSTEM ; POOR-PROGNOSIS ; RANDOMIZED-TRIAL ; OLIGODENDROGLIAL TUMORS ; IDH1 mutation ; VINCRISTINE CHEMOTHERAPY ; BRAIN-TUMOR GROUP
    Abstract: There is a lack of relevant prognostic and predictive factors in neurooncology besides mutation of isocitrate dehydrogenase 1, codeletion of 1p/19q and promoter hypermethylation of O (6) -methylguanine-DNA-methyltransferase. More importantly, there is limited translation of these factors into clinical practice. The cancer genome atlas data and also clinical correlative analyses suggest a pivotal role for the epidermal growth factor receptor /protein kinase B/mammalian target of rapamycin (mTOR) pathway in both biology and the clinical course of gliomas. However, attempts to stratify gliomas by activating alterations in this pathway have failed thus far. The tumors of 40 patients with WHO grade II gliomas without immediate postoperative genotoxic treatment and known progression and survival status at a median follow-up of 12.2 years were analyzed for expression of the mTOR complex 2 downstream target N-myc downstream regulated gene (NDRG)1 using immunohistochemistry. Baseline characteristics for NDRG1 absent/low versus moderate/high patients were similar. Time to reintervention was significantly longer in the NDRG1 group (P = 0.026). NDRG1 may become a novel biomarker to guide the decision which WHOA degrees II glioma patients may be followed without postsurgical intervention and which patients should receive genotoxic treatment early on. Validation of this hypothesis will be possible with the observational arm of the RTOG 9802 and the pretreatment step of the EORTC 22033/26032 trials.
    Type of Publication: Journal article published
    PubMed ID: 24395351
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Keywords: radiotherapy ; THERAPY ; temozolomide ; cell invasion
    Abstract: The integrin antagonist cilengitide has been explored as an adjunct with anti-angiogenic properties to standard of care temozolomide chemoradiotherapy (TMZ/RT --〉 TMZ) in newly diagnosed glioblastoma. Preclinical data as well as anecdotal clinical observations indicate that anti-angiogenic treatment may result in altered patterns of tumor progression. Using a standardized approach, we analyzed patterns of progression on MRI in 21 patients enrolled onto a phase 2 trial of cilengitide added to TMZ/RT --〉 TMZ in newly diagnosed glioblastoma. Thirty patients from the experimental treatment arm of the EORTC/NCIC pivotal TMZ trial served as a reference. MRIcro software was used to map location and extent of initial preoperative and recurrent tumors on MRI of both groups into the same stereotaxic space which were then analyzed using an automated tool of image analysis. Clinical and outcome data of the cilengitide-treated patients were similar to those of the EORTC/NCIC trial except for a higher proportion of patients with a methylated O(6)-methylguanyl-DNA-methyltransferase gene promoter. Analysis of recurrence pattern revealed neither a difference in the size of the recurrent tumor nor in the distance of the recurrences from the preoperative tumor location between groups. Overall frequencies of distant recurrences were 20 % in the reference group and 19 % (4/21 patients) in the cilengitide group. Compared with TMZ/RT --〉 TMZ alone, the addition of cilengitide does not alter patterns of progression. This analysis does not support concerns that integrin antagonism by cilengitide may induce a more aggressive phenotype at progression, but also provides no evidence for an anti-invasive activity of cilengitide in patients with newly diagnosed glioblastoma.
    Type of Publication: Journal article published
    PubMed ID: 24442484
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Keywords: brain ; IN-VIVO ; NEURITE OUTGROWTH ; INDEPENDENT PROGNOSTIC MARKER ; STEM-CELL ; DISTINCT SUBGROUPS ; Pilocytic astrocytoma ; GENETIC PROFILES ; POSTERIOR-FOSSA EPENDYMOMA ; IMMUNOHISTOCHEMICAL EXPRESSION
    Abstract: The CD24 glycoprotein is a mediator of neuronal proliferation, differentiation and immune suppression in the normal CNS, and a proposed cancer biomarker in multiple peripheral tumor types. We performed a comparative analysis of CD24 gene expression in a large cohort of pediatric and adult brain tumors (n = 813), and further characterized protein expression in tissue sections (n = 39), primary brain tumor cultures (n = 12) and a novel orthotopic group 3 medulloblastoma xenograft model. Increased CD24 gene expression was demonstrated in ependymomas, medulloblastomas, anaplastic astrocytomas and glioblastomas, although medulloblastomas displayed higher expression than all other tumor entities. Preferential expression of CD24 in medulloblastomas was confirmed at protein level by immunostaining and computerized image analysis of cryosections. Morphologies and immunophenotyping of CD24(+) cells in tissue sections tentatively suggested disparate functions in different tumor subsets. Notably, protein staining of medulloblastoma cells was associated with prominent cytoplasmic and membranous granules, enabling rapid and robust identification of medulloblastoma cells in clinical tissue samples, as well as in experimental model systems. In conclusion, our results implicate CD24 as a clinically and experimentally useful medulloblastoma immunomarker. Although our results encourage further functional studies of CD24 as a potential molecular target in subsets of brain tumors, the promiscuous expression of CD24 in vivo highlights the importance of specificity in the future design of such targeted treatment.
    Type of Publication: Journal article published
    PubMed ID: 25820321
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Keywords: MUTATIONS ; GLIOMAS ; MGMT ; OLIGODENDROGLIAL TUMORS ; GLIOBLASTOMA ; VINCRISTINE ; ISOCITRATE DEHYDROGENASE ; BRAIN-TUMOR GROUP ; LOMUSTINE ; PROCARBAZINE
    Abstract: Isocitrate dehydrogenase (IDH) mutations are beginning to drive decisions on therapy for glioma patients. Here we sought to determine the impact of adjuvant treatment in patients with IDH-mutant, 1p/19q non-codeleted secondary high-grade astrocytoma (sHGA) WHO grades III/IV. Clinical data of 109 sHGA patients grades III/IV, in addition to IDH mutation-, 1p/19q-codeletion- and MGMT-promoter methylation status-were retrospectively analyzed. Survival analysis in relation to adjuvant treatment modalities and molecular profiling were performed. Out of 109 patients, 88 patients (80.7 %) harbored IDH mutations, 30 patients had a 1p/19q-codeletion (27.5 %) and 69 patients (63.3 %) exhibited a methylated MGMT-promoter status. At a median follow-up of 9.8 years, 62 patients (57 %) died. The postsurgical treatment included: radio-chemotherapy (RT-CT; 54.5 %), RT alone (19.3 %), and CT alone (22.7 %). The median overall survival (OS) in the entire group was 3.4 years (1.9-6.7 years). Patients who received RT-CT had a significantly longer OS compared with those who underwent RT alone (6.5 vs. 1.2 years, HR 0.35, CI 0.32-0.51, p = 0.011). In the IDH-mutant 1p/19q non-codeleted sHGA subgroup the RT-CT cohort had a significantly longer OS in comparison to the RT cohort (6.4 vs. 1.2 years, HR 2.7, CI 1.1-6.5, p = 0.022). In the stepwise multivariable Cox model for OS of all 88 IDH-mutant sHGA patients, survival was strongly associated with only one factor, namely, adjuvant RT-CT at diagnosis of a sHGA. This retrospective long-term study demonstrates that RT and CT (mostly PCV) significantly improves progression-free and overall survival in IDH-mutant secondary high-grade astrocytoma patients, regardless of 1p/19q-codeletion status.
    Type of Publication: Journal article published
    PubMed ID: 26033545
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Keywords: SURVIVAL ; INHIBITION ; THERAPY ; EFFICACY ; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE ; CYCLOOXYGENASE-2 ; PHASE-II TRIAL ; ADJUVANT TEMOZOLOMIDE ; RECURRENT MALIGNANT GLIOMA ; RADIOTHERAPY PLUS CONCOMITANT
    Abstract: Chemotherapy is often omitted in elderly patients with glioblastoma multiforme due to a fear of side effects. We applied metronomic chemotherapy with low-dose temozolomide and celecoxib (LD-TEM/CEL) during and after external beam radiotherapy (EBRT) and here report on how this regimen compares to standard temozolomide radiochemotherapy (SD-TEM) in elderly patients. We retrospectively analyzed records of 146 patients aged 65 years and older that underwent EBRT. Factors of interest were age, performance status, comorbidities, MGMT status, therapy (resection/biopsy, radiotherapy/dose, chemotherapy/regimen/dose), progression-free (PFS) and overall survival (OS) status. Irrespective of the regimen, addition of chemotherapy more than doubled median survival rates (EBRT only: 4.2 months; EBRT + LD-TEM/CEL: 8.5 months; EBRT + SD-TEM: 10.8 months; p a parts per thousand currency sign 0.008). Although patients receiving metronomic LD-TEM/CEL were significantly older (62 % were a parts per thousand yen75 years vs. 22 %; p 〈 0.001), had significantly lower performance scores (50 % had a KPS 〈 70 vs. 28 %; p = 0.049) and were significantly more comorbid (73 % had a parts per thousand yen4 comorbidities vs. 37 %; p = 0.002) than patients of the SD-TEM group, there were no significant differences in PFS and OS. Independent of other factors, omission of chemotherapy significantly impairs progression-free and overall survival. With all the limitations of a retrospective analysis, our data suggest that metronomic chemotherapy with LD-TEM/CEL may be equieffective and eventually better tolerated than SD-TEM. It may be offered to elderly patients that are not eligible for standard chemotherapy.
    Type of Publication: Journal article published
    PubMed ID: 26045360
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...