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  • DKFZ Publication Database  (1,941)
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  • Articles  (2)
  • DKFZ Publication Database  (1,941)
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  • 1
    Keywords: GENE-EXPRESSION ; DIFFERENTIATION ; TUMORS ; BIOLOGY ; PROGRESSION ; PHENOTYPE ; P-TEFB ; RISK STRATIFICATION ; SUBGROUPS ; MIRNA EXPRESSION
    Abstract: Neuroblastoma, a childhood cancer that originates from neural crest-derived cells, is the most common deadly solid tumor of infancy. Amplification of the MYCN oncogene, which occurs in approximately 20-25% of human neuroblastomas, is the most prominent genetic marker of high-stage disease. The availability of valid preclinical in vivo models is a prerequisite to develop novel targeted therapies. We here report on the generation of transgenic mice with Cre-conditional induction of MYCN in dopamine beta-hydroxylase-expressing cells, termed LSL-MYCN;Dbh-iCre. These mice develop neuroblastic tumors with an incidence of 〉75%, regardless of strain background. Molecular profiling of tumors revealed upregulation of the MYCN-dependent miR-17-92 cluster as well as expression of neuroblastoma marker genes, including tyrosine hydroxylase and the neural cell adhesion molecule 1. Gene set enrichment analyses demonstrated significant correlation with MYC-associated expression patterns. Array comparative genome hybridization showed that chromosomal aberrations in LSL-MYCN;Dbh-iCre tumors were syntenic to those observed in human neuroblastomas. Treatment of a cell line established from a tumor derived from a LSL-MYCN;Dbh-iCre mouse with JQ1 or MLN8237 reduced cell viability and demonstrated oncogene addiction to MYCN. Here we report establishment of the first Cre-conditional human MYCN-driven mouse model for neuroblastoma that closely recapitulates the human disease with respect to tumor localization, histology, marker expression and genomic make up. This mouse model is a valuable tool for further functional studies and to assess the effect of targeted therapies.Oncogene advance online publication, 1 September 2014; doi:10.1038/onc.2014.269.
    Type of Publication: Journal article published
    PubMed ID: 25174395
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  • 2
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    Cancer Research 74 (17), 4671-4675 
    Keywords: CELLS ; carcinoma ; GENERATION ; TUMORS ; DISCOVERY ; senescence ; PANCREAS CANCER
    Abstract: The Helmholtz Alliance Preclinical Comprehensive Cancer Center (PCCC; www.helmholtz-pccc.de) hosted the "1st International Kloster Seeon Meeting on Mouse Models of Human Cancer" in the Seeon monastery (Germany) from March 8 to 11, 2014. The meeting focused on the development and application of novel mouse models in tumor research and high-throughput technologies to overcome one of the most critical bottlenecks in translational bench-to-bedside tumor biology research. Moreover, the participants discussed basic molecular mechanisms underlying tumor initiation, progression, metastasis, and therapy resistance, which are the prerequisite for the development of novel treatment strategies and clinical applications in cancer therapy. Cancer Res; 74(17); 4671-5. (c)2014 AACR.
    Type of Publication: Journal article published
    PubMed ID: 25136075
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  • 3
  • 4
    Keywords: - ; comparison ; UPSTREAM ; microbiology ; ENGLAND ; technique ; computational biology ; methods ; DNA-MICROARRAY ; GO ; INTERFERENCE ; SCALE ; RNA INTERFERENCE ; EXTENSION ; RE ; FEATURES ; signaling ; German ; in combination ; FALSE DISCOVERY RATE ; SIGNALING NETWORK ; signaling networks ; biotechnology ; RNA ; microarray ; GENES ; DNA ; GENE ; GENE-EXPRESSION ; NETWORK ; NETWORKS ; CELL ; Germany ; CELLS ; EXPRESSION ; CANCER CELLS ; CANCER ; PATHWAYS ; MODEL ; MODELS ; PATHWAY ; human ; COMBINATION ; STABILITY ; bioinformatics ; CANCER-CELLS ; SIGNALING PATHWAYS ; SIGNALING PATHWAY ; EFFICIENT ; RECONSTRUCTION ; BIOLOGY ; INTERVENTION ; BREAST ; breast cancer ; BREAST-CANCER ; gene expression ; MICROARRAY DATA
    Type of Publication: Book chapter
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  • 5
    Keywords: CANCER DIAGNOSIS ; THERAPIES ; DNA repair ; methods ; NEW-YORK ; GENE ; GENES ; PATIENT ; CANCER ; CELL ; carcinoma ; radiotherapy ; DIAGNOSIS ; THERAPY ; cell cycle ; CELL-CYCLE ; prognosis ; BREAST ; breast cancer ; BREAST-CANCER ; CANCER-PATIENTS ; side effects ; CANCER PATIENTS
    Type of Publication: Book chapter
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  • 6
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    Berlin, Springer
    Gliomas 25-41 
    Keywords: pathology ; TUMORS ; CANCER ; tumor ; Research ; cancer research
    Type of Publication: Book chapter
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  • 7
    Keywords: treatment ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; SUSCEPTIBILITY ; VARIANTS ; SKIN ; mechanisms ; prevention ; HEALTH ; PROMOTER ; BREAST ; breast cancer ; BREAST-CANCER ; cancer prevention ; smoking ; SNP ; REPAIR ; WOMEN ; LYMPHOCYTES ; DAMAGE ; GENOTYPES ; cancer risk ; CANCER-PATIENTS ; INDIVIDUALS ; case-control studies ; DNA-DAMAGE ; CANCER PATIENTS ; SUSCEPTIBILITY GENE ; BODY ; RISK ; GENE ; ENZYMES ; DISEASE ; lung cancer ; LUNG-CANCER ; PATIENT ; MECHANISM ; DNA ; TUMORS ; validation ; DRUG ; RNA ; GENES ; THERAPY ; VITRO ; LUNG ; COMBINATION ; CANCER ; EXPRESSION ; IN-VITRO ; CELLS ; CELL ; tumor ; AGENTS ; radiotherapy ; NSCLC ; CANCER-RISK ; cancer research ; RNA EXPRESSION ; ENZYME ; case control studies ; analysis ; GENOTYPE ; PROFILES ; single-nucleotide ; development ; PROMOTER POLYMORPHISM ; XRCC1 ; VARIANT ; WEIGHT ; SINGLE NUCLEOTIDE POLYMORPHISMS ; SNPs ; case-control study ; GEMCITABINE ; CAPACITY ; DEFICIENCY ; small cell lung cancer ; AGENT ; SINGLE ; DNA repair ; MPO ; APE1
    Abstract: Cells in the body are permanently attacked by DNA-reactive species, both from intracellular and environmental sources. Inherited and acquired deficiencies in host defense mechanisms against DNA damage (metabolic and DNA repair enzymes) can modify cancer susceptibility as well as therapy response. Genetic profiles should help to identify high-risk individuals who subsequently can be enrolled in preventive measures or treated by tailored therapy regimens. Some of our attempts to define such risk profiles are presented. Cancer susceptibility: Single nucleotide polymorphisms (SNPs) in metabolic and repair genes were investigated in a hospital-based lung cancer case-control study. When evaluating the risk associated with different genotypes for N-acetyltransferases (Wikman et al. 2001) and glutathione-S-transferases (Risch et al. 2001), it is mandatory to distinguish between the three major histological subtypes of lung tumors. A promoter polymorphism of the myeloperoxidase gene MPO was shown to decrease lung cancer susceptibility mainly in small cell lung cancer (SCLC) (Dally et al. 2002). The CYP3A4*1B allele was also linked to an increased SCLC risk and in smoking women increased the risk of lung cancer eightfold (Dally et al. 2003b). Polymorphisms in DNA repair genes were shown to modulate lung cancer risk in smokers, and reduced DNA repair capacity elevated the disease risk (Rajaee-Behbahani et al. 2001). Investigations of several DNA repair gene variants revealed that lung cancer risk was only moderately affected by a single variant but was enhanced up to approximately threefold by specific risk allele combinations (Popanda et al. 2004). Therapy response: Inter-individual differences in therapy response are consistently observed with cancer chemotherapeutic agents. Initial results from ongoing studies showed that certain polymorphisms in drug transporter genes (ABCB1) differentially affect response outcome in histological subgroups of lung cancer. Stronger beneficial effects were seen in non-small cell lung cancer (NSCLC) patients following gemcitabine and in SCLC patients following etoposide-based treatment. Several DNA repair parameters (polymorphisms, RNA expression, and DNA repair capacity) were measured in vitro in lymphocytes of patients before radiotherapy and correlated with the occurrence of acute side effects (radio-hypersensitivity). Our initial analysis of several repair gene variants in breast cancer patients (n = 446) who received radiotherapy revealed no association of single polymorphisms and the development of side effects (moist desquamation of the irradiated normal skin). The risk for this side effect was, however, strongly reduced in normal weight women carrying a combination of XRCC1 399Gln and APE1 148Glu alleles, indicating that these variants afford some protection against radio-hypersensitivity (Chang-Claude et al. 2005). Based on these data we conclude that specific metabolic and DNA repair gene variants can affect cancer risk and therapy outcome. Predisposition to hereditary cancer syndromes is dominated by the strong effects of some high-penetrance tumor susceptibility genes, while predisposition to sporadic cancer is influenced by the combination of multiple low-penetrance genes, of which as a major challenge, many disease-relevant combinations remain to be identified. Before translating these findings into clinical use and application for public health measures, large population-based studies and validation of the results will be required.
    Type of Publication: Book chapter
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  • 8
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    Springer-Verlag
    Keywords: brain tumor ; BRAIN-TUMORS ; TUMORS ; tumor ; brain ; CANCER
    Type of Publication: Book chapter
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  • 9
    Keywords: radiation therapy ; THERAPIES ; monitoring ; PATTERN ; tumor ; LUNG ; THERAPY ; imaging ; radiation ; TUMORS ; PATTERNS ; RADIATION-THERAPY ; IMRT
    Type of Publication: Book chapter
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  • 10
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    Wiley VCH
    Keywords: GENES ; TUMORS ; GENE ; tumor
    Type of Publication: Book chapter
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  • 11
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    Wiley Blackwell
    Keywords: tumor ; INVASION ; TUMORS ; PROGRESSION ; INSIGHTS ; METASTASIS
    Type of Publication: Book chapter
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  • 12
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    Wiley Blackwell
    Hereditary Tumors 501-514 
    Keywords: TUMORS ; tumor ; THERAPY ; molecular ; THERAPIES ; TARGETED THERAPY
    Type of Publication: Book chapter
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  • 13
    Keywords: CANCER ; RECEPTOR ; CELL ; tumor ; radiotherapy ; DEATH ; TUMORS ; DIFFERENTIATION ; LIGAND ; LIGANDS ; RECEPTORS ; SERIES ; resistance ; death receptor ; SOLID TUMORS ; DEATH RECEPTORS
    Type of Publication: Book chapter
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  • 14
    Keywords: MM3 ; therapeutic ; TEMPERATURE ; ACCURATE ; intensity ; HIGH-RESOLUTION ; ultrasound ; GUIDANCE ; MAGNETIC-RESONANCE ; sensitivity ; PERFORMANCE ; PROBE ; VIVO ; IN-VIVO ; tumor ; treatment ; MR ; MRI ; TUMORS ; RESOLUTION
    Abstract: High intensity contact ultrasound (HICU) under MRI guidance may provide minimally invasive treatment of endocavitary digestive tumors (colon/rectum). In this study, opposed-solenoid receiver-only coils were integrated into an endoscopic phased array ultrasound probe to offer high resolution MRI guidance of thermotherapy. The improvement of the image quality and temperature monitoring and control using this device has been investigated in- vivo, on a clinical 1.5T. The comparison endocavitary/external standard coils (voxel: 0.88 x 0.88 x 8 mm3) showed a sensitivity gain up to a factor 4, at the limit of the cooling balloon. Infra-millimeter resolution became feasible for fast MR thermometry while providing an excellent SDT. The endoscopic device was actively operated under automatic temperature control, demonstrating accurate performance.
    Type of Publication: Proceeding
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  • 15
  • 16
    Keywords: gene transfer ; GENE-TRANSFER ; GENE-EXPRESSION ; TUMORS ; GENE ; EXPRESSION ; tumor ; IN-VIVO ; imaging ; molecular imaging ; gene expression ; BIOLOGY ; TRACER ; MALIGNANT-TUMORS ; molecular ; PHAGE DISPLAY ; PHAGE
    Type of Publication: Book chapter
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  • 17
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    Springer Verlag
    Keywords: Onkologie ; abdomen ; tumor ; TUMORS ; SYSTEMS ; SYSTEM
    Abstract: Die radiologische Diagnostik nimmt in der Erkennung, Stadieneinteilung, Therapieplanung und -kontrolle sowie der Nachsorge von Tumorerkrankungen eine zentrale Stellung ein. Sie muss, in Abhängigkeit von der jeweiligen Erkrankung, speziellen Anforderungen gerecht werden. In den von behandelnden Klinikern und onkologisch erfahrenen Radiologen gemeinsam verfassten Kapiteln dieses zweibändigen Werkes werden eingehend sowohl die klinischen Grundlagen und Therapieverfahren als auch die radiologische Diagnostik zur Erkennung des Tumors, Therapieplanung und Nachsorge detailliert dargestellt. Der erste Band behandelt die soliden Tumoren oberhalb des Zwerchfells, bösartige Neubildungen des Binde- und Stützgewebes sowie des lymphatischen Systems, der zweite Band die Tumoren des Abdomens und des Beckens
    Type of Publication: Book chapter
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  • 18
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    Springer Verlag
    Keywords: TUMORS ; SYSTEM ; SYSTEMS ; tumor ; abdomen ; Onkologie ; Therapie
    Abstract: Die radiologische Diagnostik nimmt in der Erkennung, Stadieneinteilung, Therapieplanung und -kontrolle sowie der Nachsorge von Tumorerkrankungen eine zentrale Stellung ein. Sie muss, in Abhängigkeit von der jeweiligen Erkrankung, speziellen Anforderungen gerecht werden.Eingehend und detailliert stellt dieses zweibändige Werk klinische Grundlagen, Therapieverfahren und radiologische Diagnostik zur Erkennung des Tumors, Therapieplanung und Nachsorge dar.Onkologisch erfahrene Radiologen und behandelnde Kliniker verfassten die Kapitel gemeinsam. Der erste Band behandelt die soliden Tumoren oberhalb des Zwerchfells, bösartige Neubildungen des Binde- und Stützgewebes sowie des lymphatischen Systems; der zweite Band die Tumoren des Abdomens und des Beckens.Sämtliche Kapitel sind einheitlich gegliedert und bieten schnellen Zugriff für Diagnose und Therapie. Ein Standardwerk mit umfassenden Informationen aus erster Hand.
    Type of Publication: Book chapter
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  • 19
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    Springer
    Keywords: MAGNETIC-RESONANCE ; magnetic resonance ; tomography ; tumor ; TUMORS ; - ; intracranial ; RESONANCE
    Type of Publication: Book chapter
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  • 20
    Keywords: tumor ; TUMORS ; MARKER
    Type of Publication: Patent
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  • 21
    Keywords: treatment ; tumor ; TUMORS
    Type of Publication: Patent
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  • 22
    Keywords: TUMORS ; tumor ; treatment
    Type of Publication: Patent
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  • 23
    Keywords: CELLS ; EXPRESSION ; INHIBITOR ; tumor ; IN-VIVO ; GENE ; TUMORS ; ACCUMULATION ; CATECHOLAMINES ; gene therapy ; human norepinephrine transporter ; I-123 MIBG ; LINES ; METAIODOBENZYLGUANIDINE UPTAKE ; MIBG uptake ; MICE ; NEUROBLASTOMA-CELLS ; NORADRENALINE TRANSPORTER ; NUCLEAR-MEDICINE ; radiation ; RELEASE ; STORAGE ; TIME ; TRANSDUCTION
    Abstract: The transport of MIBG by the human norepinephrine transporter (hNET) seems to be the critical step in the treatment of MIBG- concentrating tumors. Therefore, we investigated whether the accumulation of MIBG may be induced by retroviral transect on of the hNET gene in Morris hepatoma cells. Methods: A bicistronic retroviral vector for the transfer of the hNET coding sequence and the hygromycin resistance gene was generated. Morris hepatoma cells (MH3924A) were infected with the respective retroviral particles, and hNET-expressing cell lines MHhNEThyg1 to MHhNEThyg9 were obtained through hygromycin selection. The uptake of H-3-norepinephrine or I-131-MIBG and the efflux of I-131-MIBG were determined in transfected and wild-type cells. In addition, the I-131-MIBG distribution was monitored in nude mice and rats bearing wild-type and hNET- expressing hepatomas. Results: hNET-expressing hepatoma cell lines accumulated up to 36 times more norepinephrine than did wild-type cells and 8 times more than did hNET-expressing neuroblastoma cell line SK-N-SH. The addition of nisoxetine, a selective inhibitor of noradrenaline uptake, inhibited norepinephrine uptake. Maximal I-131-MIBG accumulation was observed 2 h after incubation and was followed by 43% efflux within 4 h after the I-131-MIBG-containing medium had been removed. In vivo experiments performed with nude mice bearing both hNET-expressing and wild-type tumors showed a 10-fold- higher accumulation of I-131-MIBG in transfected tumors than in wild-type tumors. The ex vivo calculations revealed doses of 605 and 75 mGy in hNET-expressing and wild-type tumor tissues, respectively. Conclusion: Transduction of the hNET gene enables Morris hepatoma cells to accumulate norepinephrine and MIBG. However, the retention of MIBG is brief; therefore, the absorbed dose of radiation in vivo is not expected to be therapeutically effective
    Type of Publication: Journal article published
    PubMed ID: 12791828
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  • 24
    Keywords: CELLS ; EXPRESSION ; CELL ; Germany ; PATHWAY ; PATHWAYS ; ACETATE-NONUTILIZING MUTANTS ; CDNA ; CDNA CLONES ; CLONES ; CLONING ; CRASSA ; DISTINCT ; DNA-microarray analysis,transcriptional profiling,correspondence analysis,acetate metabolism,Neurosp ; ENZYMES ; FILAMENTOUS FUNGUS ; GENE ; GENE-EXPRESSION ; GENES ; GENOME ; GENOME SEQUENCE ; HYBRIDIZATION ; microarray ; NMT1 ; PROTEIN ; PROTEINS ; RNA ; SACCHAROMYCES-CEREVISIAE ; SAMPLE ; SAMPLES ; transcription
    Abstract: Nutrient-dependent variations in transcript levels of the filamentous fungus Neurospora crassa were studied on a microarray containing some 4700 cDNAs. Cells were grown in minimal and acetate medium. The isolated RNA was analyzed in comparison to the results obtained upon the hybridization of samples prepared from the RNA of cells grown in full medium. Altogether, 160 cDNA clones exhibited significant variations, falling into five distinct subgroups of very similar transcription profiles. This is indicative of the occurrence of a high degree of co-regulation of genes in N. crassa. Especially the regulation of the expression of proteins involved in metabolic pathways was found to be strongly regulated at the RNA level. (C) 2003 Elsevier Inc. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 14599890
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  • 25
    Keywords: CELLS ; tumor ; CELL ; Germany ; MICROSCOPY ; DIAGNOSIS ; NEW-YORK ; PROTEIN ; PROTEINS ; ADHESION MOLECULES ; cell line ; COMPONENTS ; CONSTITUTIVE TRANSMEMBRANE GLYCOPROTEIN ; CULTURED-CELLS ; DESMOCOLLIN ; desmoplakin ; desmosome ; DIFFERENTIATION ; EPITHELIA ; HUMAN PLAKOGLOBIN ; INTERMEDIATE-SIZED FILAMENTS ; meninges,meningioma,desmosome,desmocollin 3 ; meningioma ; MOLECULAR CHARACTERIZATION ; MOLECULES ; MONOCLONAL-ANTIBODY ; MR-165000 DESMOGLEIN ; NON-EPIDERMAL DESMOSOMES ; PLAQUE PROTEIN ; SUBDURAL SPACE ; TISSUE ; TUMORS
    Abstract: Intercellular junctions morphologically identical to epithelial desmosomes are known structures in meningiomas and arachnoidal tissue. Desmoplakin as one of the desmosomal plaque components has proven to be a reliable marker for diagnosis of meningeal tumors. Here we demonstrate by immunofluorescence microscopy, immunoblot and reverse transcription-PCR reactions that cells of arachnoidal tissue, of diverse meningioma subtypes and of a meningioma-derived cell line contain the full complement of the typical desmosomal proteins desmoplakin (DP), plakophilin 2 (PP2), desmocollin 2 (Dsc2) and desmoglein 2 (Dsg2). Consequently, all these molecules are suitable for diagnostic applications of meningioma tumors. In addition to these constitutive desmosomal components, representative for single-layered (simple) epithelia, the dural border cells of the arachnoid and about 60% of the meningiomas tested were positive for desmocollin 3 (Dsc3), a protein in epithelia taken as an indicator for differentiation
    Type of Publication: Journal article published
    PubMed ID: 12845453
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  • 26
    Keywords: EXPRESSION ; INHIBITOR ; Germany ; KINASE ; GENE ; GENES ; PROTEIN ; SACCHAROMYCES-CEREVISIAE ; transcription ; COMPONENTS ; COMPLEX ; COMPLEXES ; cell cycle ; CELL-CYCLE ; CYCLE ; protein kinase ; PROTEIN-KINASE ; IDENTIFICATION ; gene expression ; protein kinase CK2 ; Saccharomyces cerevisiae ; SUBUNIT ; YEAST ; BUDDING YEAST ; DISRUPTION ; EXPRESSION ANALYSIS ; HOLOENZYME ; PHO pathway
    Abstract: The budding yeast Saccharomyces cerevisiae encounters phosphate starvation by the transcription-regulated PHO pathway. We find that genetic perturbation of protein kinase CK2, a conserved tetrameric Ser/Thr phosphotransferase with links to cell cycle and transcription, affects expression of PHO pathway genes in a subunit- and isoform-specific manner. Remarkably, the genes encoding phosphate supplying phosphatases and transporters are significantly repressed, while the genes encoding components of the central pathway regulator complex, a cyclin-dependent kinase (CDK), a cyclin, and a CDK inhibitor, remain unaltered. Thus, perturbation of CK2 uncouples the executive part of the PHO pathway from its cyclin-CDK control complex. (C) 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies
    Type of Publication: Journal article published
    PubMed ID: 12606059
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  • 27
    Keywords: EXPRESSION ; screening ; DISTINCT ; GENE ; GENES ; GENOME ; DNA ; FAMILY ; ASSOCIATION ; autistic disorder,susceptibility gene,chromosome 2,mutation screening,association ; CANDIDATE GENE ; chromosome ; DISORDER ; DLX GENES ; FREQUENCY ; GENOMEWIDE SCREEN ; GENOMIC SCREEN ; GLUTAMIC-ACID DECARBOXYLASE ; LINKAGE ; polymorphism ; POLYMORPHISMS ; SIGNAL ; single nucleotide polymorphism ; SUSCEPTIBILITY ; SUSCEPTIBILITY GENES ; SUSCEPTIBILITY LOCUS ; VARIANTS
    Abstract: The results from several genome scans indicate that chromosome 2q21-q33 is likely to contain an autism susceptibility locus. We studied the potential contribution of nine positional and functional candidate genes: TBR-1; GAD1; DLX1; DLX2; cAMP-GEFII; CHN1; ATF2; HOXD1 and NEUROD1. Screening these genes for DNA variants and association analysis using intragenic single nucleotide polymorphisms did not provide evidence for a major role in the aetiology of autism. Four rare nonsynonymous variants were identified, however, in the cAMP-GEFII gene. These variants were present in five families, where they segregate with the autistic phenotype, and were not observed in control individuals. The significance of these variants is unclear, as their low frequency in IMGSAC families does not account for the relatively strong linkage signal at the 2q locus. Further studies are needed to clarify the contribution of cAMP-GEFII gene variants to autism susceptibility
    Type of Publication: Journal article published
    PubMed ID: 14593429
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  • 28
    Keywords: CANCER ; PROTECTION ; MODEL ; DISEASE ; EPIDEMIOLOGY ; HISTORY ; RISK ; GENE ; GENES ; SAMPLE ; FAMILY ; RISK-FACTORS ; SUSCEPTIBILITY ; BREAST ; breast cancer ; BREAST-CANCER ; AGE ; BRCA1 ; case-only design ; family history ; gene carrier probability ; LINKAGE ANALYSIS ; mixture logistic model ; ovarian cancer ; OVARIAN-CANCER ; population and sibling controls ; WOMEN
    Abstract: Background The effect of environmental/lifestyle factors on breast cancer risk may be modified by genetic predisposition. Methods In a population-based case-control-family study performed in Germany including 706 cases by age 50 years, 1381 population, and 252 sister controls, we investigated main effects for environmental/lifestyle factors and genetic susceptibility and gene-environment interaction (G x E). Different surrogate measures for genetic predisposition using pedigree information were used: first-degree family history of breast or ovarian cancer; and gene carrier probability using a genetic model based on rare dominant genes. Possible G x E interaction was studied by (1) logistic regression using cases and population controls including an interaction term; (2) comparing results using sister controls and population controls; (3) case-only analysis with logistic regression and (4) a mixture logistic model. Results Familial predisposition showed the strongest main effect and the estimated gene carrier probability gave the best fit. High parity and longer duration of breastfeeding reduced breast cancer risk significantly, a history of abortions increased risk and age at menarche showed no significant effect. We found significant G x E interaction between parity and genetic susceptibility using different surrogate measures. In women most likely to have a high genetic susceptibility, high parity was less protective. Later age at menarche was protective in women with a positive family history. No evidence for G x E interaction was found for breastfeeding and abortion. Conclusions These findings corroborate results from other studies and provide further evidence that the magnitude of protection from parity is reduced in women most likely to have a genetic risk in spite of the limitations of using surrogate genetic measures
    Type of Publication: Journal article published
    PubMed ID: 12690006
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  • 29
    Keywords: SURVIVAL ; tumor ; Germany ; INHIBITION ; MODEL ; MODELS ; DISEASE ; DISEASES ; incidence ; liver ; RISK ; SITE ; SITES ; GENE ; TUMORS ; STORAGE ; TIME ; PATIENT ; NITRIC-OXIDE SYNTHASE ; INJURIES ; DNA ; INFECTION ; RISK-FACTORS ; CARCINOGENESIS ; RAT ; RATS ; PROTEIN-KINASE ; treatment ; virus ; prevention ; STRESS ; risk factors ; metastases ; DAMAGE ; chemoprevention ; COLON CARCINOGENESIS ; copper toxicity ; curcumin ; ETHENO-DNA ADDUCTS ; HEREDITARY HEPATITIS ; LEC rats ; LIPID-PEROXIDATION ; MOUSE FIBROBLAST CELLS ; NIH 3T3 ; ORNITHINE DECARBOXYLASE ; OXIDATIVE STRESS
    Abstract: Long-Evans Cinnamon (LEC) rats, an inbred mutant strain which accumulates copper due to an aberrant copper-transporting ATPase gene, develop acute hepatitis, chronic liver injury and liver tumors as a result of copper-induced oxidative stress, lipid peroxidation and DNA damage. Curcumin, an antioxidant and anti-inflammatory agent, has shown anticancer properties in many rodent models. We investigated the modulating role of curcumin in liver and kidney carcinogenesis in LEC rats. Two groups of 4-week-old LEC rats (n = 60 each) were fed either a standard diet (control) or received 0.5% curcumin in the diet for life. In untreated LEC rats, the rate of acute liver failure, the incidence of liver tumors and of kidney tumors were 32, 100 and 10% respectively, which was not altered by curcumin treatment. However, curcumin reduced tumor incidence at other organ sites (15% versus 0%; P = 0.025) and suppressed formation of metastases (18% versus 0%; P = 0.01). Median survival time was decreased from 88.7 to 78.1 weeks in curcumin-treated rats (P = 0.002). The lack of chemoprevention of liver and kidney tumors in LEC rats by curcumin may be caused by enhanced toxicity and oxidative stress due to excess copper. We conclude that curcumin should be contra-indicated for patients suffering from inherited and acquired metal storage diseases that include patients with hepatitis C virus infection. (C) 2002 Elsevier Science B.V. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 12628510
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  • 30
    Keywords: EXPRESSION ; tumor ; carcinoma ; CELL ; Germany ; TYROSINE KINASE ; screening ; SITE ; SITES ; DISTINCT ; microarray ; PROTEIN ; TISSUE ; TUMORS ; primary ; GROWTH-FACTOR RECEPTOR ; FREQUENCY ; FREQUENCIES ; STAGE ; PROGRESSION ; immunohistochemistry ; ABERRATIONS ; HEAD ; ONCOPROTEIN ; CARCINOMAS ; NECK ; squamous cell carcinoma ; GREECE ; gene amplification ; head and neck ; laryngeal carcinoma ; OROPHARYNGEAL ; C-MYC ; CANCER PATIENTS ; CYCLIN D1 OVEREXPRESSION ; cytogenetic aberration ; head and neck squamous cell carcinoma (HNSCC) ; immunohistochemistry (IHC) ; MICROARRAY ANALYSIS ; oncoprotein overexpression ; OVEREXPRESSION ; POOR-PROGNOSIS ; tissue microarray (TMA) ; tumor classification
    Abstract: Background: Tissue microarray (TMA) analysis is a high-throughput approach that allows the screening of large tumor collectives for cytogenetic aberrations. In this study, a TMA of a large collection of clinically well-defined primary squamous cell carcinomas of the head and neck (HNSCC) was used to determine the expression of several oncoproteins. Materials and Methods: A TMA containing 547 primary HNSCC was used for the analysis of cyclinD1, c-myc, erbb1 and erbb2 expression by immunohistochemistry (IHC). Results: CyclinD1 and c-myc were overexpressed at higher frequencies in primary pharyngeal and laryngeal carcinomas compared with primary oral carcinomas (p 〈 0.001 and p 〈 0.001), while erbb1 and erbb2 overexpression was associated with oral site (p 〈 0.001 and p = 0.04, respectively). Furthermore, cyclinD1 overexpression correlated with stage IV primary carcinomas (p = 0.04). Conclusion: HNSCC is a heterogenous group of tumors, which, depending on anatomic sites and clinical stage, shows variable expressions of the oncoproteins described. This indicates a specific pathogenic role of these oncoproteins in different subtypes of HNSCC and may have therapeutic implications
    Type of Publication: Journal article published
    PubMed ID: 14666705
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  • 31
    Keywords: APOPTOSIS ; CANCER ; CANCER CELLS ; CELLS ; EXPRESSION ; INHIBITOR ; tumor ; TUMOR-CELLS ; CELL ; Germany ; human ; IN-VIVO ; INHIBITION ; DEATH ; GENE ; GENE-EXPRESSION ; RNA ; TUMORS ; ACTIVATION ; PROTEIN FAMILY ; INDUCTION ; SUSCEPTIBILITY ; TARGET ; gene expression ; resistance ; HUMAN-TUMORS ; STIMULI ; CANCER-CELLS ; DELIVERY ; MAMMALIAN-CELLS ; SMALL INTERFERING RNAS ; doxorubicin ; HUMAN-TUMOR-CELLS ; IAP PROTEINS ; POSITIVE CANCER-CELLS ; RNA interference,inhibitors of apoptosis,chemotherapy,HeLa,melanoma ; STRATEGIES
    Abstract: Increased resistance to apoptosis is a hallmark of many tumor cells. The functional inhibition of specific antiapoptotic factors may provide a rational basis for the development of novel therapeutic strategies. We investigated here whether the RNA interference (RNAi) technology could be used to increase the apoptotic susceptibility of cancer cells. As a molecular target, we chose the antiapoptotic livin (ML-IAP, KIAP) gene, which is expressed in a subset of human tumors. We identified vector-borne small interfering (si)RNAs, which could efficiently block endogenous livin gene expression. Silencing of livin was associated with caspase-3 activation and a strongly increased apoptotic rate in response to different proapoptotic stimuli, such as doxorubicin, UV-irradiation, or TNFalpha. The effects were specific for Livin-expressing tumor cells. Our results (i) provide direct evidence that the intracellular interference with livin gene expression resensitizes human tumor cells to apoptosis, (ii) define the livin gene as a promising molecular target for therapeutic inhibition, and (iii) show that the livin gene is susceptible to efficient and specific silencing by the siRNA technology
    Type of Publication: Journal article published
    PubMed ID: 14614456
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    Keywords: CELLS ; EXPRESSION ; tumor ; BLOOD ; carcinoma ; human ; MICROSCOPY ; liver ; PROTEIN ; PROTEINS ; TUMORS ; FAMILY ; RAT ; hepatocytes ; MEMBER ; MEMBERS ; antibodies ; MOUSE ; IDENTIFICATION ; RAT-LIVER ; MEMBRANE ; metastases ; CONJUGATE ; LOCALIZATION ; EPITHELIAL-CELLS ; HEPATOCYTE CANALICULAR ISOFORM ; METASTATIC CARCINOMAS ; MULTIDRUG-RESISTANCE PROTEIN ; POLYPEPTIDE OATP2
    Abstract: Transport proteins mediating the selective uptake of organic anions into human hepatocytes include the organic anion transporters SLC21A6 (also termed OATP2, OATP-C, or LST-1) and SLC21A8 (OATP8). Both transporters are localized to the basolateral membrane of human hepatocytes. Because of the importance of these transporters for hepatobiliary elimination, including the removal of bilirubin and its conjugates from the blood circulation, we have generated monoclonal antibodies for studies on the expression and localization of these transport proteins. We describe two antibodies, designated monoclonal antibody MDQ (mMDQ) and monoclonal antibody ESL (mESL), directed against the amino terminus and the carboxyl terminus of human SLC21A6, respectively. Both antibodies have been characterized by immunoblot analysis, immunoprecipitation, and immunofluorescence microscopy. While mESL reacted specifically with SLC21A6, mMDQ detects both SLC21A6 and SLC21A8. Neither of the two antibodies reacted with other human, or with dog, rat, or mouse liver SLC21A family members. Antibody mMDQ may be used for the simultaneous detection of SLC21A6 and SLC21A8 in immunoblotting because of its immunoreactivity with both molecules and because of the different molecular masses of both glycosylated proteins in human hepatocytes. This is exemplified in hepatocellular carcinomas where SLC21A6 and SLC21A8 were differentially synthesized and showed an irregular staining pattern. Both transport proteins have not been detected in human hepatoma HepG2 cells. In routine paraffin sections, 10 of 12 hepatocellular carcinomas were focally positive with antibody mMDQ. In contrast, cholangiocarcinomas and liver metastases of colorectal and pancreatic adenocarcinoma were negative without exception. This suggests the usefulness of SLC21A6/SLC21A8 within a panel of tumor markers for hepatocellular carcinomas. Moreover, both antibodies should be useful in studies on the expression and localization of two important uptake transporters of human hepatocytes under physiologic and pathophysiologic conditions
    Type of Publication: Journal article published
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    Keywords: CANCER CELLS ; CELLS ; EXPRESSION ; tumor ; carcinoma ; CELL ; Germany ; human ; DISEASE ; NEW-YORK ; DISTINCT ; GENE ; GENE-EXPRESSION ; GENES ; microarray ; RNA ; cell line ; TISSUE ; validation ; LINES ; MARKER ; TISSUES ; tumour ; CELL-LINES ; BREAST-CANCER ; TARGET ; immunohistochemistry ; gene expression ; affymetrix ; CELL-LINE ; LINE ; MARKERS ; CARCINOMAS ; adenocarcinoma ; OVEREXPRESSION ; PERIPHERAL-BLOOD ; GASTRIC-CANCER ; ADAM9 ; CDNA MICROARRAYS ; cell lines ; expression profiling ; HUMAN GENES ; K-RAS ; METALLOPROTEASE-DISINTEGRIN ; microarray hybridisation ; microdissection ; OLIGONUCLEOTIDE ARRAYS ; pancreatic cancer ; pancreatic carcinoma ; SERIAL ANALYSIS
    Abstract: In a search for new molecular markers of pancreatic ductal adenocarcinoma (PDAC), we compared the gene expression profiles of seven pancreatic carcinomas and one carcinoma of the papilla Vateri with those of duct cells from three non-neoplastic pancreatic tissues. In addition, the human pancreatic duct cell line and five PDAC cell lines (AsPC-1, BxPC-3, Capan-1, Capan-2, HPAF) were examined. RNA was extracted from microdissected tissue or cultured cell lines and analysed using a custom-made Affymetrix Chip containing 3023 genes, of which 1000 were known to be tumour associated. Hierarchical clustering revealed 81 differentially expressed genes. Of all the genes, 26 were downregulated in PDAC and 14 were upregulated in PDAC. In PDAC cell lines versus normal pancreatic duct cells, 21 genes were downregulated and 20 were upregulated. Of these 81 differentially expressed genes, 15 represented human genes previously implicated in the tumourigenesis of PDAC. From the genes that were so far not known to be associated with PDAC tumorigenesis, we selected ADAM9 for further validation because of its distinct overexpression in tumour tissue. Using immunohistochemistry, the over-expressed gene, ADAM9, was present in 70% of the PDACs analysed. In conclusion, using microarray technology we were able to identify a set of genes whose aberrant expression was associated with PDAC and may be used to target the disease
    Type of Publication: Journal article published
    PubMed ID: 12942322
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    Keywords: CANCER ; carcinoma ; SYSTEM ; HEPATOCELLULAR-CARCINOMA ; incidence ; liver ; POPULATION ; RISK ; RISKS ; GENE ; GENES ; FAMILY ; primary ; tumour ; MEMBER ; MEMBERS ; ASSOCIATION ; CANDIDATE GENE ; SUSCEPTIBILITY ; AGE ; ovarian cancer ; OVARIAN-CANCER ; CERVICAL-CANCER ; bladder cancer ; BLADDER-CANCER ; SWEDEN ; DATABASE ; SIR ; familial risk ; CARRIERS ; FAMILY-CANCER DATABASE ; bile duct ; BILE-DUCTS ; CHOLECYSTECTOMY ; GALLBLADDER-CANCER ; RELATIVES ; VIRAL-HEPATITIS
    Abstract: Background and aims: Familial risks in liver and biliary cancers have been assessed in small case control studies, usually based on reported, but not medically verified, cancers in family members. Thus the degree of familial clustering for these cancers remains to be established. Methods: The nationwide Swedish Family-Cancer Database was used, covering 10.2 million individuals for the years 1961-1998 from the Swedish Cancer Registry. Liver and biliary tract cancers were identified from 1121 offspring between the ages of 0 and 66 years and 17 131 parents. Standardised incidence ratios (SIRs) and 95% confidence intervals (Cls) were calculated for cancers in family members. Results: All cancers in the liver and biliary system showed a familial SIR of 1.65 (95% Cl 1.05- 2.46). This was mainly explained by a high risk for familial gall bladder cancer (SIR 5.21 (95% Cl 2.07-10.80)) and for familial primary liver cancer with hepatocellular carcinoma histology (SIR 4.69 (95% Cl 1.48-11.04)). For gall bladder and hepatocellular cancer, maternal transmission appeared to be favoured. Gall bladder cancer was associated with pancreatic cancer (SIR 2.39 (95% Cl 1.23-4.18)). Primary liver cancer was associated with cervical, urinary bladder, and endocrine gland tumours. Cancer in extrahepatic bile ducts was associated with ovarian cancer and that in ampulla of Vater with thyroid cancer; however, these associations may have been fortuitous. Conclusions: This study has provided the first data on familial clustering of liver and gall bladder cancers, based on medically confirmed records. The risks were so high that heritable factors were likely to contribute, possibly modified by environmental factors. The demonstration of candidate genes would help to further characterise the familial risks
    Type of Publication: Journal article published
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    Keywords: CANCER ; tumor ; carcinoma ; neoplasms ; FOLLOW-UP ; RISK ; RISKS ; SITE ; SITES ; TISSUE ; TUMORS ; primary ; RISK-FACTORS ; SKIN ; treatment ; ASSOCIATION ; BREAST-CANCER ; PATTERNS ; WOMEN ; leukemia ; SWEDEN ; DATABASE ; HEREDITARY ; SIR ; familial risk ; SMALL-INTESTINE ; BRCA2 MUTATIONS ; germline mutations ; double primaries ; endometrioid tumor ; FAMILY-CANCER DATABASE ; FIRST- DEGREE RELATIVES ; heritable effects ; HODGKINS- DISEASE ; multiple primaries ; NONPOLYPOSIS COLORECTAL-CANCER ; second carcinoma ; synchronous carcinoma
    Abstract: BACKGROUND. Population-based data on subsequent neoplasms after women are diagnosed with endometrial and ovarian carcinomas are limited, particularly regarding specific histologic tumor types. METHODS. The nationwide Swedish Family-Cancer Database of 10.2 million individuals, which includes 19,128 invasive endometrial carcinomas and 19,440 ovarian carcinomas, was used to calculate standardized incidence ratios (SIRs) and 95% confidence intervals (95% CIs) for second primary carcinomas. SIRs were calculated for specific follow-up periods. Data on histopathologic types also were used. RESULTS. An excess of subsequent malignancies after women were diagnosed with endometrial carcinoma was noted at 11 sites. The highest SIRs were recorded for synchronous or metasynchronous ovarian carcinomas (SIR, 55.77; 95% CI, 48.82-63.43) and carcinomas of the small intestines (SIR, 14.71; 95% Cl, 4.64-34.59). Primary ovarian carcinoma was followed by an increased risk of developing endometrial carcinoma, and the risks of developing many other malignancies also were increased after women were diagnosed with endometrial carcinoma, including intestinal malignancies, renal cell carcinoma, bladder carcinoma, squamous cell skin carcinoma, connective tissue malignancies, and leukemia. When ovarian endometrioid histology was diagnosed synchronously with primary endometrial carcinoma, the SIR was 140; when endometrial carcinoma was the subsequent neoplasm, the SIR was 87. A small familial component was found in the cooccurrence of endometrial carcinoma and ovarian carcinoma. CONCLUSIONS. The current data show a strong clustering of endometrial carcinomas and ovarian carcinomas, particularly involving tumors of endometrioid morphology. The patterns of second neoplasms also suggest that hereditary nonpolyposis colorectal. carcinoma may contribute to the association between endometrial and ovarian malignancies. Increased risks for connective tissue tumors and leukemia may signal a response to treatment, and an increased risk for squamous cell skin carcinoma may signal a depressed immune function. (C) 2003 American Cancer Society
    Type of Publication: Journal article published
    PubMed ID: 12733142
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    Keywords: CANCER ; Germany ; EPIDEMIOLOGY ; incidence ; RISK ; RISKS ; GENE ; GENES ; SUSCEPTIBILITY ; SUSCEPTIBILITY GENES ; BREAST ; breast cancer ; BREAST-CANCER ; IDENTIFICATION ; prevention ; DESIGN ; DIFFERENCE ; AGE ; BRCA1 ; WOMEN ; SWEDEN ; DATABASE ; REGION ; MUTATIONS ; MORPHOLOGY ; SIR ; familial risk ; NATIONWIDE ; FAMILY-CANCER DATABASE ; RELATIVES ; familial risk,half sisters,risk factors,sibling risk ; INTERPRETING FAMILY ; SUSCEPTIBILITY GENE
    Abstract: Purpose. The familial risk of female breast cancer is somewhat less than 2.0 when a first-degree relative is diagnosed with breast cancer, but it is not known to what extent heritable or environmental factors explain the familial clustering. Such data would be valuable for prevention and gene identification strategies.Experimental design. We used the nation-wide Swedish Family-Cancer Database on 10.2 million individuals and 190,000 mothers' and 26,000 daughters' breast cancers to calculate familial standardised incidence ratios (SIRs), for all invasive breast cancers in daughters, who were 0-66 years old. Over 5500 familial breast cancers were recorded.Results. The familial SIR for all invasive breast cancer was 1.71 by breast cancer in the mother only, 1.95 by breast cancer in a sister only, and 2.75 by breast cancer in both a mother and sister. The SIRs did not change when adjustments were done for period, age at first birth, parity, socio-economic status and region. Age difference between sisters showed a small variation in risk for breast cancer but the highest SIR was found for those whose age difference was from 6 to 10 years. Half sisters showed an excess of familial risks exactly half of full sisters, the SIR being 1.44.Conclusions. These data suggest that familial aggregation of breast cancer is mainly due to heritable causes. Because the known susceptibility genes only explain about a quarter of the familial aggregation, the remaining majority offers a challenge to new genomic approaches
    Type of Publication: Journal article published
    PubMed ID: 14672399
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    Keywords: SPECTRA ; CANCER ; tumor ; CELL ; Germany ; DISEASE ; NEW-YORK ; CLONES ; GENE ; HYBRIDIZATION ; cell line ; TUMORS ; LINES ; primary ; CELL-LINES ; chromosome ; IN-SITU ; AMPLIFICATION ; chromosome 2 ; COMPARATIVE GENOMIC HYBRIDIZATION ; COPY NUMBER ; COPY-NUMBER ; LYMPHOMA ; ABERRATIONS ; FISH ; REGIONS ; ONCOGENE ; SEGMENTS ; FLUORESCENCE ; IMBALANCES ; cytogenetic aberration ; fluorescence in situ hybridization ; Hodgkin's lymphoma ; JAK2 ; JUMPING TRANSLOCATIONS ; REL ; telomeric segment translocation ; YAC
    Abstract: Four Hodgkin's lymphoma cell lines (KM-H2, HDLM-2, L428, L1236) were analyzed for cytogenetic aberrations, applying multiplex fluorescence in situ hybridization, chromosome banding and comparative genomic hybridization. Each line was characterized by a highly heterogeneous pattern of karyotypic changes with a large spectrum of different translocated chromosomes (range 22- 57). A recurrent finding in all cell lines was the presence of chromosomal rearrangements of the short arm of chromosome 2 involving the REL oncogene locus. Furthermore, multiple translocated copies of telomeric chromosomal segments were frequently detected. This resulted in a copy number increase of putative oncogenes, e.g., JAK2 (9p24) in 3 cell lines, FGFR3 (4p16) and CCND2 (12p13) in 2 cell lines as well as MYC (8q24) in I cell line. Our data confirm previous cytogenetic results from primary Hodgkin's tumors suggesting an important pathogenic role of REL and JAK2 in this disease. In addition, they provide evidence for a novel cytogenetic pathomechanism leading to increased copy numbers of putative oncogenes from terminal chromosomal regions, most probably in the course of chromosomal stabilization by telomeric capture. (C) 2002 Wiley- Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 12478664
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    Keywords: OPTIMIZATION ; CANCER ; radiotherapy ; CLINICAL-TRIAL ; COMBINATION ; Germany ; THERAPY ; SYSTEM ; SYSTEMS ; TUMORS ; PATIENT ; QUALITY ; IONS ; treatment ; PROTON ; VERIFICATION ; RADIATION-THERAPY ; CLINICAL-TRIALS ; BEAM ; helium ; HEAVY-IONS ; SKULL BASE ; INTENSITY-MODULATED RADIOTHERAPY ; treatment planning ; CONSTRUCTION ; EUROPE ; OXYGEN ; GATED RADIOTHERAPY ; heavy ion radiotherapy,treatment planning,clinical results,dosimetry ; ION RADIOTHERAPY ; IRRADIATION SYSTEM ; QUALITY-ASSURANCE
    Abstract: Starting with the pioneering work at the University of California in Berkeley in 1977, heavy ion radiotherapy has been of increasing interest especially in Japan and Europe in the last decade. There are currently 3 facilities treating patients with carbon ions, two of them in Japan within a clinical setting. In Germany, a research therapy facility is in operation and the construction of a new hospital based facility at the Heidelberg university will be started soon. An outline of the current status of heavy ion radiotherapy is given with emphasis to the technical aspects of the respective facilities. This includes a description of passive and active beam shaping systems, as well as their implications for treatment planning and dosimetry. The clinical trials and routine treatments performed at the German heavy ion facility are summarized.An overview over the upcoming new facilities and their technical possibilities is given. It is discussed what the necessary improvements are to fully exploit the potential of these facilities. Especially the new Heidelberg facility with the possibility of active beam scanning in combination with the first isocentric gantry for ions and offering beams of protons, helium, oxygen and carbon ions has implications on treatment planning, dosimetry and quality assurance. The necessary and ongoing developments in these areas are summarized. The new facilities also offer the possibilities to perform more extensive clinical studies and to explore future indications for radiotherapy with heavy ions. An overview over the indications and treatment schemes is also given
    Type of Publication: Journal article published
    PubMed ID: 14529303
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    Keywords: CANCER ; EXPRESSION ; SURVIVAL ; tumor ; carcinoma ; Germany ; FOLLOW-UP ; GENE-EXPRESSION ; PROTEIN ; DIFFERENTIATION ; TUMORS ; LINES ; TIME ; PATIENT ; primary ; ANTIGEN ; BIOLOGY ; ASSOCIATION ; MOLECULE ; BREAST ; breast cancer ; BREAST-CANCER ; antibodies ; antibody ; IDENTIFICATION ; PROGRESSION ; immunohistochemistry ; MALIGNANCIES ; DESIGN ; OVARIAN-CANCER ; CARCINOMA-CELLS ; BREAST-CARCINOMA ; PARAMETERS ; MULTIVARIATE ; CARCINOMAS ; FOLLOW-UP TIME ; P-SELECTIN ; CD24 ; CELL MONOCLONAL-ANTIBODIES ; protein expression
    Abstract: Purpose: CD24 is expressed in hematological malignancies as well as in a large variety of solid tumors including breast cancer. We aimed to evaluate CD24 protein expression in breast cancer and to correlate to clinicopatbological data including patient survival.Experimental Design: Primary breast carcinomas (201) with a mean clinical follow-up time of 53 months were immunostained using a monoclonal CD24 antibody (Ab-2, clone 24C02). The staining was evaluated as negative versus positive for statistical analysis.Results: In invasive breast carcinomas, CD24 expression was observed in 84.6% of cases. In univariate survival analyses, a significant association of CD24 expression with shortened patient overall survival (5-year survival rate 91.9% versus 83.8%; P = 0.031; log rank test) and disease-free survival (5-year progression rate 88.3% versus 57.0%; P = 0.0008) was demonstrated. In multivariate analyses CD24, tumor grading and nodal status were significant prognostic parameters for shortened disease-free survival.Conclusions: Our data suggest that CD24 expression in primary breast cancer as detected by immunohistochemistry might be a new marker for a more aggressive breast cancer biology
    Type of Publication: Journal article published
    PubMed ID: 14581365
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