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  • 1
    Unknown
    Berlin : de Gruyter
    Call number: W20.5:7 ; H0600:117 ; H0700:58 ; ATV-MED:115
    Keywords: Genetics, Biochemical ; Genetics, Medical ; Molecular Biology / trends ; Oncogenes
    Pages: xvi, 497 p. : ill.
    ISBN: 3-11-015097-2
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    W20.5:7 available
    H0600:117 departmental collection or stack – please contact the library
    H0700:58 departmental collection or stack – please contact the library
    ATV-MED:115 departmental collection or stack – please contact the library
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    Keywords: CANCER ; IRRADIATION ; radiotherapy ; SURVIVAL ; tumor ; COMBINATION ; Germany ; THERAPY ; FOLLOW-UP ; imaging ; incidence ; radiation ; PATIENT ; kidney ; treatment ; MALIGNANCIES ; EXPERIENCE ; RADIATION-THERAPY ; RATES ; RECURRENCE ; RESECTION ; CHILDREN ; FAILURE ; SARCOMA ; ONCOLOGY-GROUP ; neuroblastoma ; MALIGNANCY ; ONCOLOGY ; CHILDHOOD ; GRADE ; SOLID TUMORS ; STENOSIS ; methods ; NUCLEAR ; LOSSES ; BONE ; CHILD ; pediatric ; SARCOMAS ; soft-tissue sarcoma ; external beam radiotherapy ; EXTREMITY SARCOMAS ; intraoperative radiotherapy ; ONCOLOGY GROUP ; pediatric cancer ; STAGE-C NEUROBLASTOMA
    Abstract: Purpose: Intrauperative electron-beam radiotherapy (IOERT) has been applied for local dose escalation in over 1,400 patients in Heidelberg since 1991. Among these were 30 children, in 18 of whom IOERT was employed in radiation treatment with external-beam radiotherapy (EBRT) on account of incomplete resection. We address the question whether IOERT is able to compensate for microscopic or macroscopic tumor residue if employed in the overall radiation regimen. Methods and Materials: The data of the aforementioned 18 children were analyzed with regard to local recurrence, overall survival, and complication rates. All children suffered from either sarcomas or neuroblastomas. In all children, IOERT was employed for local dose escalation after or before EBRT. Results: After a median follow-up of 60.5 months, 15 of the treated children are alive. One local failure has been observed. Six children show clinically significant late morbidity, including the loss of a treated limb (Radiation Therapy Oncology Group Grade 4 [RTOG 4]), a severe nerve lesion (RTOG 3), an orthopedic complication (RTOG 2), a ureteral stenosis (not clinically significant), and a kidney hypotrophy (not clinically significant). In I child a fracture due to radionecrosis (RTOG 4) was diagnosed; however, in the follow-up, local tumor relapse was diagnosed as another possible reason for the fracture. Conclusions: Regarding the low incidence of local failure, IOERT seems to be able to compensate incomplete tumor resection in childhood sarcoma and neuroblastoma patients. The incidence of late morbidity is low enough to justify the employment of IOERT as part of the radiation treatment regimen for pediatric patients. (c) 2006 Elsevier Inc
    Type of Publication: Journal article published
    PubMed ID: 16257132
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  • 4
    Keywords: APOPTOSIS ; CANCER ; CELLS ; GROWTH ; INHIBITOR ; SURVIVAL ; tumor ; TUMOR-CELLS ; CELL ; Germany ; KINASE ; THERAPY ; GENE-EXPRESSION ; DIFFERENTIATION ; ACTIVATION ; primary ; prognosis ; CELL-CYCLE ; ANTITUMOR-ACTIVITY ; TARGET ; NERVOUS-SYSTEM ; BONE-MARROW-TRANSPLANTATION ; STRATEGIES ; CHILDREN ; REPRESSION ; RETINOIC ACID ; 13-CIS-RETINOIC ACID ; INHIBITORS ; ONCOLOGY ; RE ; TUMOR-SUPPRESSOR ; THERAPIES ; LEVEL ; SUPPRESSOR ; USA ; BREAST-CANCER CELLS ; cell cycle arrest ; E2F-1 regulated genes ; epigenetic therapy ; HC-TOXIN ; HUMAN NEURO-BLASTOMA ; RB tumor suppressor network
    Abstract: The survival rate of children with advanced neuroblastoma (NB) is dismal despite intensive multimodal therapy. The limited efficacy and the frequent and serious side effects of currently used therapeutic regimens necessitate the development of new, less toxic treatment strategies. This study shows that the histone deacetylase inhibitor Helminthosporium carbonum (HC)-toxin suppresses the malignant phenotype of both established NB cell lines and primary NB cells with and without amplified MYCN at dosages lower than 20 nM. HC-toxin induces cell cycle arrest and apoptosis as well as neuronal differentiation and diminishes both colony formation and invasive growth. These cellular changes are accompanied by the transcriptional repression of cell cycle regulators of the retinoblastoma (RB) tumor suppressor network found at high levels in NBs with poor prognosis, like E2F-1 and its targets Skp2, N-myc, Mad2 and survivin. The levels of the hypophosphorylated active form of RB, and of cyclin-dependent kinase inhibitors including P15(INK4b), p16(INK4a), p21(cip1/waf-1) and p27(kip1) are increased. In conclusion, nanomolar doses of the HDACI HC-toxin cause a shift to a differentiated and benign phenotype of NB cells that is associated with an activation of the RB tumor suppressor network. (c) 2007 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 18074352
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  • 5
    Keywords: CANCER ; CELLS ; GROWTH ; IN-VITRO ; INHIBITOR ; SURVIVAL ; tumor ; CELL ; Germany ; VITRO ; GENE-EXPRESSION ; PROTEIN ; PROTEINS ; DIFFERENTIATION ; ACTIVATION ; primary ; CELL-LINES ; ANTITUMOR-ACTIVITY ; culture ; ACID ; RATES ; CELL-LINE ; acetylation ; HIGH-RISK ; HISTONE DEACETYLASE ; Ras ; retinoids ; neuroblastoma ; N-MYC ; ONCOLOGY ; RE ; TUMOR-SUPPRESSOR ; LEVEL ; HISTONE DEACETYLASE INHIBITORS ; SUPPRESSOR ; SODIUM VALPROATE ; retinoblastoma ; tumor suppressor ; HC-TOXIN ; RB tumor suppressor network ; E2F-1 ; HIGH-RISK NEUROBLASTOMA ; SUPPRESSES
    Abstract: Treatment of high-risk neuroblastoma (NB) is difficult. Novel therapeutics improving survival rates are urgently required. We have previously shown that the histone deacetylase inhibitor (HDACI) Helminthosporium carbonum (HC)toxin induces differentiation of neuroblastoma (NB) cells. Here, we show that HC-toxin inhibits the growth of both established NB cell lines and primary cultures with and without amplified MYCN stronger than retinoids (RAs) and other HDACIs (MS-275, n-butyric acid, suberoylanilide hydroxamic acid, trichostatin A, valproic acid). Nanomolar dosages suppress E2F-1, N-myc, Skp2, Mad2 and survivin proteins, found at high levels in high-risk NBs, more efficiently than both RAs and other HDACIs. The level of hypophosphorylated active retinoblastoma (RB) tumor suppressor protein is increased most effectively. HC-toxin's epoxy group is essential for inhibiting HDACs and promoting anti-NB activity. Without this functional group, those cellular effects are not observed. In conclusion, the anti-NB activity of HC-toxin is superior to that of RAs and that of all other HDACIs tested. (C) 2008 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 18262346
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  • 6
    Keywords: tumor ; Germany ; THERAPY ; CT ; imaging ; INFORMATION ; TOOL ; VISUALIZATION ; VOLUME ; NEW-YORK ; DIFFERENTIATION ; TUMORS ; computed tomography ; NUCLEAR-MEDICINE ; PATIENT ; kidney ; MRI ; MAGNETIC-RESONANCE ; magnetic resonance imaging ; TRIAL ; TRIALS ; METASTASIS ; chemotherapy ; COMPUTED-TOMOGRAPHY ; CHILDREN ; nuclear medicine ; MANAGEMENT ; PREOPERATIVE CHEMOTHERAPY ; radiology ; ONCOLOGY ; CHILDHOOD ; THERAPIES ; monitoring ; NUCLEAR ; USA ; EXTENT ; CHILD ; pediatric ; BONE METASTASES ; nephroblastoma ; SIOP ; MEDICINE ; three-dimensional ; INTERNATIONAL-SOCIETY ; PARTIAL NEPHRECTOMY ; IMAGING CHARACTERISTICS ; INTRAVASCULAR EXTENSION ; UNILATERAL WILMS-TUMOR
    Abstract: Magnetic resonance imaging (MRI) presents the main diagnostic tool for differentiation and staging of renal tumors in childhood. Nephroblastoma is the most common malignant tumor in children. Radiological findings play an important role in therapy study trials of SIOP (International Society of Pediatric Oncology), especially for indicating preoperative chemotherapy. In the past few years MRI has gained great importance in imaging of nephroblastoma and has replaced computed tomography (CT). The aim of this review is to present the diagnostic possibilities of MRI in relation to the requirements of therapy studies. For nephroblastoma, MRI provides important information about tumor extent and distant metastasis. A special focus of MRI in distant staging is venous extent of the tumor into the inferior vena cava. In addition, MRI has an important role in monitoring chemotherapy and in preoperative planning by volume rendering and three-dimensional postprocessing
    Type of Publication: Journal article published
    PubMed ID: 18193429
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  • 7
    Keywords: brain ; radiotherapy ; SURVIVAL ; Germany ; THERAPY ; DIAGNOSIS ; FOLLOW-UP ; imaging ; VOLUME ; LONG-TERM ; POPULATION ; radiation ; TIME ; PATIENT ; IMPACT ; TARGET ; RADIATION-THERAPY ; AGE ; MALES ; RATES ; PROGNOSTIC-FACTORS ; RESECTION ; PROGNOSTIC FACTORS ; LOW-GRADE ASTROCYTOMAS ; CHILDREN ; MR imaging ; GLIOMAS ; THERAPIES ; GLIOMA ; radiation therapy ; fractionated stereotactic radiotherapy ; LOW-GRADE GLIOMA ; HIGH-GRADE GLIOMAS ; SYMPTOMS ; PEDIATRIC-ONCOLOGY-GROUP ; NERVOUS-SYSTEM TUMORS ; EXTENT ; GLIOBLASTOMA ; PHASE-I/II TRIAL ; PROGRESSION-FREE SURVIVAL ; outcome ; WELL ; BEAM IRRADIATION ; Brain stem gliomas ; HYPERFRACTIONATED RADIATION-THERAPY ; MEDICAL-CENTER ; PONTINE GLIOMAS
    Abstract: Introduction: To assess long-term outcome in 85 patients with brain stem gliomas treated with fractionated stereotactic radiation therapy (FSRT). Patient and methods: Thirty-nine patients were females, and 46 were males. Median age at primary diagnosis was 26 years. Thirty-one patients were younger than 18 years. Histopathological examination confirmed a low-grade glioma in 57 patients. Of the group of high-grade gliomas, six were anaplastic astrocytomas, and two were classified as glioblastoma. Patient and methods: Radiation therapy was performed as FSRT. The median target volume was 101 nil. We applied a median dose of 54 Gy in conventional fractionation of 1.8 Gy. In seven of 85 patients (8%) FSRT was performed as re-irradiation. Results: The median follow-up time was 42 months. Median overall survival (OS) was 81 months. OS rates were 77% at 12 months, 70% at 24 months, and 63% at 36 months. Significant impact on OS could be shown for pilocytic histology, age, neurosurgical resection as well as for the presence of cyst on MR-imaging. Results: Median progression-free survival (PFS) after FSRT was 52 months. PFS rates at 12 months were 70%, and 63% and 58% at 24 and 36 months. respectively. Results: Histology, partial neurosurgical resection and the duration of symptoms could be identified as significant prognostic factors. Conclusion: Long-term outcome of FSRT in patients with brain stem gliomas is acceptable with low rates of side effects. Significant impact on outcome could be shown for histology. age, extent of neurosurgical resection as well as for cyst formation. No dose-response relationship could be observed. (C) 2009 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 91 (2009) 60-66
    Type of Publication: Journal article published
    PubMed ID: 19285356
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  • 8
    Keywords: CELLS ; EXPRESSION ; Germany ; VOLUME ; DISEASE ; GENES ; PATIENT ; kidney ; ACID ; chemotherapy ; HIGH-RISK ; CHILDREN ; RETINOIC ACID ; signaling ; development ; USA ; nephroblastoma ; WILMS-TUMOR ; pediatrics ; nephroblastomatosis ; von Willebrand disease ; Wilms Tumor
    Abstract: A 9-month-old girl presented with massive bilateral diffuse nephroblastomatosis. After response to actinomycin D and vincristine over a period of 1 year, the nephroblastomatosis continuously progressed under this treatment. As retinoic acid signaling is critical for normal renal development and nephroblastomatosis seems histologically as undifferentiated embryonal tissue, we added 13-cis retinoic acid to the chemotherapy regimen. Three months thereafter, kidney volumes declined significantly over a period of 1 year. Interestingly, nephroblastomatosis-associated acquired von Willebrand disease also resolved. Retinoic acid maybe a novel nontoxic treatment option for nephroblastomatosis requiring further systematic evaluation
    Type of Publication: Journal article published
    PubMed ID: 19346886
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  • 9
    Abstract: Despite multimodal therapeutic concepts, advanced localized and high-risk neuroblastoma remains a therapeutic challenge with a long-term survival rate below 50%. Consequently, new modalities for the treatment of neuroblastoma, e.g., oncolytic virotherapy are urgently required. H-1PV is a rodent parvovirus devoid of relevant pathogenic effects in infected adult animals. In contrast, the virus has oncolytic properties and is particularly cytotoxic for transformed or tumor-derived cells of various species including cells of human origin. Here, a preclinical in vitro assessment of the application of oncolytic H-1PV for the treatment of neuroblastoma cells was performed. Infection efficiency, viral replication and lytic activity of H-1PV were analyzed in 11 neuroblastoma cell lines with different MYCN status. Oncoselectivity of the virus was confirmed by the infection of short term cultures of nonmalignant infant cells of different origin. In these nontransformed cells, no effect of H-1PV on viability or morphology of the cells was observed. In contrast, a lytic infection was induced in all neuroblastoma cell lines examined at MOIs between 0.001 and 10 pfu/cell. H-1PV actively replicated with virus titres increasing up to 5,000-fold within 48-96 hr after infection. The lytic effect of H-1PV was observed independent of MYCN oncogene amplification or differentiation status. Moreover, a significant G2-arrest and induction of apoptosis could be demonstrated. Infection efficiency, rapid virus replication and exhaustive lytic effects on neuroblastoma cells together with the low toxicity of H-1PV for nontransformed cells, render this parvovirus a promising candidate for oncolytic virotherapy of neuroblastoma.
    Type of Publication: Journal article published
    PubMed ID: 20087864
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  • 10
    Keywords: brain ; tumor ; Germany ; neoplasms ; TOOL ; HYBRIDIZATION ; DIFFERENTIATION ; TUMORS ; MARKER ; BIOLOGY ; IN-SITU ; AMPLIFICATION ; AGE ; ABERRATIONS ; FISH ; CENTRAL-NERVOUS-SYSTEM ; pathology ; CHILDREN ; BEHAVIOR ; CHROMOSOMES ; FEATURES ; brain tumor ; BRAIN-TUMORS ; PRIMITIVE NEUROECTODERMAL TUMORS ; LOCUS ; diagnostic marker ; ABUNDANT NEUROPIL ; TRUE ROSETTES ; 19q13 ; Embryonal brain tumor ; Ependymoblastoma ; ETANTR ; Molecular diagnosis ; WHO classification of CNS tumors
    Abstract: Ependymoblastoma (EBL) and embryonal tumor with abundant neuropil and true rosettes (ETANTR) are very aggressive embryonal neoplasms characterized by the presence of ependymoblastic multilayered rosettes typically occurring in children below 6 years of age. It has not been established whether these two tumors really comprise distinct entities. Earlier, using array-CGH, we identified a unique focal amplification at 19q13.42 in a case of ETANTR. In the present study, we investigated this locus by fluorescence in situ hybridization in 41 tumors, which had morphologically been diagnosed as EBL or ETANTR. Strikingly, FISH analysis revealed 19q13.42 amplifications in 37/40 samples (93%). Among tumors harboring the amplification, 19 samples were identified as ETANTR and 18 as EBL. The three remaining tumors showed a polysomy of chromosome 19. Analysis of recurrent/metastatic tumors (n = 7) showed that the proportion of nuclei carrying the amplification was increased (up to 80-100% of nuclei) in comparison to the corresponding primary tumors. In conclusion, we have identified a hallmark cytogenetic aberration occurring in virtually all embryonal brain tumors with ependymoblastic rosettes suggesting that ETANTR and EBL comprise a single biological entity. FISH analysis of the 19q13.42 locus is a very promising diagnostic tool to identify a subset of primitive neuroectodermal tumors with distinct morphology, biology, and clinical behavior
    Type of Publication: Journal article published
    PubMed ID: 20407781
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