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  • Articles  (1)
  • DKFZ Publication Database  (1,104)
  • GENES
  • 1
    ISSN: 1573-7039
    Keywords: BRCA1 ; BRCA2 ; BREAST CANCER ; OVARIAN CANCER ; CANCER SUSCEPTIBILITY ; GENES ; MUTATION DETECTION
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this article, we review the history oftesting for mutations in breast cancer susceptibilitygenes and discuss the current state of testing formutations in BRCA1 and BRCA2 in different clinicalsettings including at-risk individuals and cancerpatients. The risk of breast cancer, other associatedmalignancies and prognosis in carriers of thesemutations are reviewed. A final section includesdiscussion of current recommendations for surveillance andthe need for further research to identify environmentaland genetic factors which modify the risk of developingcancer in mutation carriers.
    Type of Medium: Electronic Resource
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  • 2
    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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  • 3
    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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  • 4
    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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  • 5
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    Keywords: GENES ; TUMORS ; GENE ; tumor
    Type of Publication: Book chapter
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  • 6
  • 7
    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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  • 8
    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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  • 9
    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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  • 10
    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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  • 11
    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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  • 12
    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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  • 13
    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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  • 14
    Keywords: APOPTOSIS ; CELL ; evaluation ; Germany ; human ; PATHWAY ; PATHWAYS ; SYSTEM ; SYSTEMS ; GENE ; GENES ; PROTEIN ; PROTEINS ; DRUG ; TRANSDUCTION ; DNA ; MECHANISM ; prognosis ; INDUCTION ; mechanisms ; signal transduction ; treatment ; SIGNAL ; VARIANTS ; DISCOVERY ; TARGET ; TRANSPORT ; IDENTIFICATION ; MALIGNANCIES ; resistance ; DNA-REPAIR ; REPAIR ; SIGNAL-TRANSDUCTION ; chemotherapy ; MELANOMA ; PRODUCT ; MALIGNANT-MELANOMA ; TARGETS ; malignant melanoma ; drug resistance ; DRUG-RESISTANCE ; MULTIDRUG-RESISTANCE ; TRAIL ; DNA repair ; N-RAS ; EFFECTOR ; ACQUIRED-RESISTANCE ; CHEMOSENSITIZES HUMAN-MELANOMA ; drug resistance,melanoma,apoptosis ; METASTATIC MALIGNANT-MELANOMA ; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE ; PROTEIN MRP ; SCID MICE ; SOUTHWEST-ONCOLOGY-GROUP ; TRAIL-INDUCED APOPTOSIS
    Abstract: In malignant melanoma chemotherapy is very ineffective. This poor prognosis largely results from resistance to conventional chemotherapy. The cellular mechanisms involved in melanoma chemoresistance have yet to be fully elucidated. The relevance of well analyzed drug-resistance mechanisms such as intra-/extracellular transport, drug-resistance by induction of certain enzyme systems and DNA repair is reviewed. The results of many studies suggest that drug resistance in melanoma is most likely caused by a dysregulation of apoptotic processes. Identification of genes and gene products that are responsible for apoptosis, together with emerging information about the mechanism of action and structures of apoptotic regulatory and effector proteins, has laid a foundation for the discovery of drugs, some of which are now undergoing evaluation in human clinical trails for melanoma treatment. The complexity of the molecular variants involved in signal transduction along apoptotic pathways suggests that the cell may have a variety of possibilities for regulating apoptosis and generating apoptosis deficiency. However, identification of drug resistance mechanisms provides new therapeutic targets to overcome chemoresistance in this and other malignancies
    Type of Publication: Journal article published
    PubMed ID: 14709935
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  • 15
    Keywords: RECEPTOR ; APOPTOSIS ; CELLS ; AGENTS ; human ; KINASE ; DISEASE ; LONG-TERM ; GENE ; GENES ; PROTEIN ; DRUG ; PATIENT ; ACTIVATION ; primary ; TRANSPLANTATION ; INDUCTION ; T-CELLS ; BINDING ; protein kinase ; TARGET ; CELL-DEATH ; INDUCED APOPTOSIS ; MODULATION ; LYMPHOCYTES ; CROHNS-DISEASE ; INFLAMMATORY-BOWEL-DISEASE ; 6- MERCAPTOPURINE ; CD28 ; COLITIS IN-VIVO ; GTPASE
    Abstract: Azathioprine and its metabolite 6-mercaptopurine (6-MP) are immunosuppressive drugs that are used in organ transplantation and autoimmune and chronic inflammatory diseases such as Crohn disease. However, their molecular mechanism of action is unknown. In the present study, we have identified a unique and unexpected role for azathioprine and its metabolites in the control of T cell apoptosis by modulation of Rac1 activation upon CD28 costimulation. We found that azathioprine and its metabolites induced apoptosis of T cells from patients with Crohn disease and control patients. Apoptosis induction required costimulation with CD28 and was mediated by specific blockade of Rac1 activation through binding of azathioprine- generated 6-thioguanine triphosphate (6-Thio-GTP) to Rac1 instead of GTP. The activation of Rac1 target genes such as mitogen-activated protein kinase kinase (MEK), NF-kappaB, and bcl-x(L), was suppressed by azathioprine, leading to a mitochondrial pathway of apoptosis. Azathioprine thus converts a costimulatory signal into an apoptotic signal by modulating Rac1 activity. These findings explain the immunosuppressive effects of azathioprine and suggest that 6-Thio-GTP derivates may be useful as potent immunosuppressive agents in autoimmune diseases and organ transplantation
    Type of Publication: Journal article published
    PubMed ID: 12697733
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  • 16
    Keywords: EXPRESSION ; CELL ; Germany ; GENES ; PROTEIN ; PROTEINS ; PATIENT ; SKIN ; MELANOMA ; METASTATIC MELANOMA ; CANCER-PATIENTS ; ANTIBODY-RESPONSES ; CANCER/TESTIS ANTIGENS ; MELANOMA PATIENTS ; cancer-testis antigens,DNA screening,humoral response,HYREX,SEREX ; CYTOLYTIC T-LYMPHOCYTES ; HUMAN TUMOR-ANTIGENS ; HUMORAL IMMUNE-RESPONSES
    Type of Publication: Journal article published
    PubMed ID: 12932233
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  • 17
    Keywords: APOPTOSIS ; CANCER ; CELLS ; EXPRESSION ; tumor ; CELL ; Germany ; human ; THERAPY ; DEATH ; GENE ; GENE-EXPRESSION ; GENES ; PROTEIN ; SACCHAROMYCES-CEREVISIAE ; DRUG ; NEUROBLASTOMA-CELLS ; FAMILY ; PROTEIN FAMILY ; DOMAIN ; CONTRAST ; MEMBER ; MEMBERS ; SEQUENCE ; SIGNAL ; BREAST-CANCER ; cytokines ; ACID ; ACIDS ; PROGRESSION ; ENCODES ; YEAST ; resistance ; CELL-DEATH ; PLASMA ; MEMBRANE ; INTERFERON ; sensitization ; AMINO-ACIDS ; OVEREXPRESSION ; MYCN ; neuroblastoma ; DRUG-INDUCED APOPTOSIS ; MAPS ; DISULFIDE BOND FORMATION ; EGG-WHITE ; INDUCED CELL DEATH ; QUIESCIN Q6 ; RETINOID COMBINATION ; THIOREDOXIN REDUCTASE
    Abstract: In neuroblastoma cells, apoptotic programs can be activated by cytokines and cytostatic drugs. Apoptotic dysfunction confers resistance against therapeutic drugs and is a major complication for achieving optimal therapy response. Deregulated expression of the MYCN gene is a critical determinant in neuroblastoma progression, and one of the pleiotropic functions of the MYCN protein is cellular sensitization to cytokine-induced and drug-induced apoptosis. By using the functional approach of technical knockout (TKO), we have identified five genes that regulate sensitization for IFN-gamma-induced cell death. Most efficient among them is the newly identified SOXN (neuroblastoma-derived sulfhydryl oxidase), which comprises 12 exons and maps to 9q34.3. SOXN encodes a putative protein of 698 amino acids that contains a signal sequence, a protein-disulfide-isomerase-type thioredoxin and a yeast ERV1 domain and is highly homologous to members of the sulfhydryl oxidase/Quiescin6 family. The SOXN protein is predominantly located in the plasma and in the nuclear membrane. Antisense SOXN confers resistance to IFN-gamma-induced apoptosis. In contrast, ectopic overexpression of sense-SOXN sensitizes the cells to induced cell death. These results identify SOXN as a major player in regulating the sensitization of neuroblastoma cells for IFN-gamma-induced apoptosis
    Type of Publication: Journal article published
    PubMed ID: 14633699
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  • 18
    Keywords: EXPRESSION ; CELL ; Germany ; GENE ; GENES ; transcription ; MOLECULAR CHARACTERIZATION ; TISSUE ; MECHANISM ; TRANSCRIPTION FACTOR ; REDUCTION ; TISSUES ; mechanisms ; TARGET ; MUTANT ; STAGE ; TRANSCRIPTION FACTORS ; IDENTIFICATION ; IN-SITU ; MICROARRAY DATA ; NUMBER ; RT-PCR ; sensitivity ; max ; expression profiling ; TRANSCRIPTIONAL REGULATION ; COMPLEXITY ; MOLECULAR-MECHANISM ; ARABIDOPSIS-THALIANA ; BETA-GLUCOSIDASE ; CELL-WALL PROTEIN ; FLORAL ORGAN IDENTITY ; GENOME-WIDE ANALYSIS ; GERBERA-HYBRIDA ; HOMEOTIC GENE ; LIPID-TRANSFER PROTEIN
    Abstract: The class B MADS box transcription factors DEFICIENS (DEF) and GLOBOSA (GLO) of Antirrhinum majus together control the organogenesis of petals and stamens. Toward an understanding of how the downstream molecular mechanisms controlled by DEF contribute to petal organogenesis, we conducted expression profiling experiments using macroarrays comprising 〉11,600 annotated Antirrhinum unigenes. First, four late petal developmental stages were compared with sepals. More than 500 ESTs were identified that comprise a large number of stage-specifically regulated genes and reveal a highly dynamic transcriptional regulation. For identification of DEF target genes that might be directly controlled by DEF, we took advantage of the temperature-sensitive def-101 mutant. To enhance the sensitivity of the profiling experiments, one petal developmental stage was selected, characterized by increased transcriptome changes that reflect the onset of cell elongation processes replacing cell division processes. Upon reduction of the DEF function, 49 upregulated and 52 downregulated petal target genes were recovered. Eight target genes were further characterized in detail by RT-PCR and in situ studies. Expression of genes responding rapidly toward an altered DEF activity is confined to different petal tissues, demonstrating the complexity of the DEF function regulating diverse basic processes throughout petal morphogenesis
    Type of Publication: Journal article published
    PubMed ID: 15539471
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  • 19
    Keywords: CANCER ; EXPRESSION ; carcinoma ; CELL ; Germany ; LUNG ; COMMON ; lung cancer ; LUNG-CANCER ; EXPOSURE ; RISK ; GENE ; GENES ; HYBRIDIZATION ; DNA ; MECHANISM ; primary ; RISK-FACTORS ; mechanisms ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; SUSCEPTIBILITY ; NO ; AMPLIFICATION ; AGE ; DNA-REPAIR ; REPAIR ; CIGARETTE-SMOKING ; risk factors ; smoking ; PCR ; cancer risk ; DAMAGE ; RISK FACTOR ; REGION ; CARCINOGENS ; adenocarcinoma ; case-control studies ; squamous cell carcinoma ; INDIVIDUALS ; CANCER-RESEARCH ; SMOKERS ; NUCLEOTIDE EXCISION-REPAIR ; CELL CARCINOMA ; case control study ; case-control study ; REGRESSION ; OCCUPATIONAL-EXPOSURE ; CARCINOGEN ; HEAVY ; LUNG ADENOCARCINOMA ; PIGMENTOSUM GROUP-A
    Abstract: Polymorphisms of genes coding for DNA repair can affect lung cancer risk. A common single nucleotide (-4) G-to-A polymorphism was identified previously in the 5' untranslated region of the XPA gene. In a case-control study in European Caucasians, the influence of this polymorphism on primary lung cancer risk overall and according to histologic subtypes was investigated. Four hundred sixty-three lung cancer cases (including 204 adenocarcinoma and 212 squamous cell carcinoma) and 460 tumor-free hospital controls were investigated using PCR amplification and melting point analysis of sequence-specific hybridization probes. Odds ratios (OR) were calculated by multiple logistic regression analysis adjusting for age, gender, smoking habits, and occupational exposure and showed a slightly enhanced risk for all lung cancer cases as well as for squamous cell carcinoma and adenocarcinoma cases. Gene-environment interactions were analyzed with respect to smoking and occupational exposure. A nearly 3-fold increased risk for adenocarcinoma associated with the XPA AA genotype was observed for occupationally exposed individuals (OR, 2.95; 95% confidence interval, 1.42-6.14) and for heavy smokers (OR, 2.52; 95% confidence interval, 1.17-5.42). No genotype-dependent increase in OR was found for nonexposed individuals or those smoking 〈20 pack-years. The significant effect of the XPA polymorphism in heavy smokers and occupationally exposed individuals suggests an important gene-environment interaction for the XPA gene. The underlying mechanisms as to why AA homozygotes are predisposed to lung adenocarcinoma and which specific carcinogens are involved remains to be determined
    Type of Publication: Journal article published
    PubMed ID: 15598786
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  • 20
    Keywords: CELLS ; CELL ; Germany ; human ; MICROSCOPY ; CLASSIFICATION ; IMAGES ; NETWORKS ; screening ; GENE ; GENES ; GENOME ; PROTEIN ; PROTEINS ; EFFICIENCY ; CULTURED-CELLS ; COMPLEX ; COMPLEXES ; BIOLOGY ; MOLECULAR-BIOLOGY ; IDENTIFICATION ; PATTERNS ; ASSAY ; microarrays ; ARRAYS ; genetics ; REQUIRES ; LOCALIZATION ; Jun ; MORPHOLOGY ; PHENOTYPE ; FUNCTIONAL GENOMICS ; CDNAS ; molecular biology ; molecular ; RE ; PATTERN ; LIGHT ; ARRAY ; genomics ; PATTERN-RECOGNITION ; proteome ; TRANSFECTION
    Abstract: Light microscopic analysis of cell morphology provides a high-content readout of cell function and protein localization. Cell arrays and microwell transfection assays on cultured cells have made cell phenotype analysis accessible to high-through put experiments. Both the localization of each protein in the proteome and the effect of RNAi knock-down of individual genes on cell morphology can be assayed by manual inspection of microscopic images. However, the use of morphological readouts for functional genomics requires fast and automatic identification of complex cellular phenotypes. Here, we present a fully automated platform for high-throughput cell phenotype screening combining human live cell arrays, screening microscopy, and machine-learning-based classification methods. Efficiency of this platform is demonstrated by classification of eleven subcellular patterns marked by GFP-tagged proteins. Our classification method can be adapted to virtually any microscopic assay based on cell morphology, opening a wide range of applications including large-scale RNAi screening in human cells
    Type of Publication: Journal article published
    PubMed ID: 15173118
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  • 21
    Keywords: CELLS ; EXPRESSION ; tumor ; CELL ; Germany ; human ; PATHWAY ; GENE ; GENE-EXPRESSION ; GENES ; DIFFERENTIATION ; TUMORS ; COMPLEX ; COMPLEXES ; INDUCTION ; CONTRAST ; SKIN ; LOCALIZATION ; BENIGN ; keratin ; skin tumors ; epidermis ; FOLLICLE ; HAIR-FOLLICLES ; HUMAN TYPE-I ; MATRIX ; BETA-CATENIN EXPRESSION ; CORTEX ; HAIR FOLLICLE ; hair follicles,human,transcription factors,tumors ; HOXC13 ; INVOLUCRIN
    Abstract: Human hair follicles exhibit a complex pattern of sequential hair keratin expression in the hair matrix, cuticle, and cortex. In pilomatricomas, that is, benign skin tumors thought to arise from germinative matrix cells of the hair follicle and retaining morphological signs of cortical differentiation, this differential hair keratin pattern has been shown to be faithfully preserved in the lower and upper transitional cell compartments of the tumors. Here we show that also the co-expression of hair keratin hHa5 with its regulatory nuclear homeoprotein HOXC13 in matrix cells of the hair follicle is maintained in lower transitional cells of pilomatricomas. In contrast, the nuclear co-expression of LEF1 and beta-catenin, which in the hair follicle has been postulated to initiate cortex cell differentiation through the induction of hair keratin hHa1 expression (Merill et al, Genes Dev 15:1688-1705, 2001), is not preserved in upper transitional cells of pilomatricomas. Although these cells correctly express hHa1, they are completely devoid of LEF1 and nuclear LEF1/beta-catenin co-expression is shifted to a subpopulation of hair keratin-free basaloid cells of the tumors. These data imply that unlike the normal hair follicle, cortical differentiation in pilomatricomas is not under the control of the canonical Wnt signaling pathway
    Type of Publication: Journal article published
    PubMed ID: 15140206
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  • 22
    Keywords: PEPTIDE ; CANCER ; CELLS ; EXPRESSION ; GROWTH ; tumor ; TUMOR-CELLS ; carcinoma ; CELL ; Germany ; human ; THERAPY ; GENE ; GENE-EXPRESSION ; GENES ; transcription ; LINES ; INFECTION ; INTERVENTION ; FLOW ; cell cycle ; CELL-CYCLE ; CYCLE ; E7 ; ACID ; ACIDS ; NUCLEIC-ACIDS ; gene expression ; p53 ; HIGH-RISK ; DNA-DAMAGE ; drug delivery ; HPV ; E6 ; EPITHELIAL-CELLS ; Jun ; PHENOTYPE ; CARCINOMAS ; CARRIERS ; HUMAN-PAPILLOMAVIRUS TYPE-16 ; INFECTIONS ; human papilloma virus ; BEHAVIOR ; FLOW-CYTOMETRY ; TUMOR CELLS ; ANTAGONIST ; PNA ; anti-gene ; cell-cycle-drug-effects ; EARLY GENES ; flow cytometry ; HPV type ; HUMAN CANCER ; immortalization ; oncogene-protein-E6 ; oncogeneprotein-E7 ; P53 GENE ; papillomaviruses ; peptide nucleic acid ; PRB ; RNA INTERFERENCE ; THERAPIES
    Abstract: Approximately 100% of cervical carcinomas are causally linked to infections with high-risk human papillomaviruses (HPVs), whose oncogenicity has been assigned to the continued expression of two early viral genes, E6 and E7. Reversal of the transformed phenotype by inhibiting E6/E7 gene expression therefore provides a suitable goal for tumor therapy. We established an application controlling the E6/E7 expression of the HPV type 18, by using viral gene directed peptide nucleic acids (PNAs). One consequence was the complete change in growth to a stagnated behavior of the HPV 18 positive HeLa-S cells. With flow cytometry, we investigated changes in the cell cycle and expression of the pRB (retinoblastoma) and p53 genes acting as antagonists to E6 and E7. We realized that application of PNAs via intracellular cleavable conjugated peptide carriers mediates specific inhibitory effects and we showed that the combined E6/E7-directed PNA-application mediated a clear morphological change from suspension to adherend state and the cells stopped growth. These data could demonstrate a promising approach for development of new 'anti-gene therapeutics' against papillomavirus-induced human cancers. (C) 2004 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 15145519
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  • 23
    Keywords: Germany ; CT ; HISTORY ; GENE ; GENES ; DNA ; animals ; ACID ; ESCHERICHIA-COLI ; REGION ; SIALIC-ACID ; CELL-ADHESION MOLECULE ; N-ACETYLNEURAMINIC ACID ; 2-KETO-3-DEOXY-D-GLYCERO-D-GALACTO-NONONIC ACID ; 8-PHOSPHATE SYNTHASE ; NEISSERIA-MENINGITIDIS ; POLYSACCHARIDE BIOSYNTHESIS ; SYNTHETASE
    Abstract: alpha-Ketoacids are present in glycosylated structures in almost all organisms and must be activated by a cytidylyltransferase (CT) before their incorporation into glycoconjugates. Examples of alpha-ketoacids include KDO (keto-deoxyoctulosonic acid), which is present in bacterial lipopolysaccharide and in plant pectins, and sialic acids (Sia), such as N-acetylneuraminate (NeuAc), which are present in animals and in pathogenic microorganisms. The phylogeny of Sia and CTs is unclear but is linked to the history of the alpha-ketoacid synthases. Furthermore, horizontal gene transfer (HGT) events might have played a major role. Here we analyse the origin and the expansion process of these genes with respect to the taxonomic coherence of the phylogenetic trees, the molecular characteristics of the CT-coding DNA and the presence or absence of a long C-terminal coding region in some NeuAc-CTs. We propose a prokaryotic origin for CTs and et-ketoacid synthases, and a HGT event of these genes towards ancestors of animals and plants. Finally, some pathogenic bacteria reacquired some of these genes, which would have been modified and devoted to Sia synthesis
    Type of Publication: Journal article published
    PubMed ID: 15001188
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  • 24
    Keywords: CANCER ; CANCER CELLS ; CELLS ; EXPRESSION ; GROWTH ; IN-VITRO ; proliferation ; tumor ; TUMOR-CELLS ; carcinoma ; CELL ; CELL-PROLIFERATION ; Germany ; human ; IN-VIVO ; MODEL ; PATHWAY ; PATHWAYS ; PROSTATE ; VITRO ; VIVO ; SYSTEM ; DEATH ; GENE ; GENE-EXPRESSION ; GENES ; microarray ; COMPONENTS ; DIFFERENTIATION ; primary ; cell cycle ; CELL-CYCLE ; TARGET ; gene expression ; CARCINOMA CELLS ; METASTASIS ; prostate cancer ; PROSTATE-CANCER ; metastases ; COMPONENT ; LINE ; SURFACE ; CARCINOMA-CELLS ; ADHESION ; RT-PCR ; TUMOR CELLS ; prostate carcinoma ; ONCOLOGY ; transcript profiling ; quantitative RT-PCR ; cell adhesion ; cell proliferation ; HUMAN PROSTATE ; osteoblast ; osteomimicry ; prostate cancer metastasis
    Abstract: Bone metastasis is the primary cause of death in human prostate cancer. Disseminated from primary tumor and distributed via the bloodstream, a proportion of prostate carcinoma cells eventually reach the skeleton and develop into metastases, requiring adhesion to inner bone surfaces lined by osteoblasts. The crosstalk of tumor cells with osteoblasts is a critical but poorly characterized step in the metastatic process. Using an in vitro metastasis model system, we have been examining effects of osteoblast-re leased factors on gene expression of prostate carcinoma cells. Here, we show by large-scale transcript profiling and quantitative RT-PCR that osteoblast-released factors target in particular the proliferation and adhesion regulons of tumor cells. Genes encoding components of the cell-cycle control machinery and connected pathways are predominantly repressed and cell proliferation is slowed down, resembling in vivo observations assumed to render commonly used chemotherapeutic measures ineffective. Genes encoding anchoring junction components are predominantly elevated, and the adhesion properties of tumor cells are altered. Moreover, prostate carcinoma cells are provoked to undergo osteomimicry, i.e., to express bone cell-related genes. The data indicate that the crosstalk with osteoblasts induces expressional changes in prostate carcinoma cells favoring the bone colonization process. (C) 2004 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 15185357
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  • 25
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    Differentiation 72 (2-3), 74-80 
    Keywords: EXPRESSION ; Germany ; MODEL ; PATHWAY ; PATHWAYS ; TOOL ; GENE ; GENE-EXPRESSION ; GENES ; GENOME ; PROTEIN ; PROTEINS ; RNA ; MECHANISM ; MESSENGER-RNA ; mechanisms ; BINDING ; BIOLOGY ; SEQUENCE ; DISCOVERY ; TARGET ; MOUSE ; IDENTIFICATION ; gene expression ; Drosophila ; CELL-DEATH ; CAENORHABDITIS-ELEGANS ; DEGRADATION ; PREDICTION ; TARGETS ; DOUBLE-STRANDED-RNA ; C-ELEGANS ; GENETIC INTERFERENCE ; miRNA,RNAi,gene silencing,target prediction,development,Drosophila
    Abstract: MicroRNAs (miRNAs) represent a growing class of short non-coding RNAs that regulate gene expression by post-transcriptional mechanisms. By binding to target mRNAs via stretches of sequence complementarity, microRNAs inhibit the production of target proteins or induce degradation of mRNAs. Several hundred miRNAs have recently been predicted and cloned from eukaryotic organisms as diverse as plants, invertebrates, and vertebrates. Some miRNAs were shown to be widely conserved across phyla. However, except in a few described cases, rather little is known about their endogenous target genes and the physiological pathways they impinge on. Invertebrate model organisms such as C. elegans and Drosophila have been instrumental to develop methods and to dissect biological roles of miRNAs. In this review, we will focus on recent progress in characterizing miRNAs and steps toward identification of target genes in Drosophila. Many of these recent experiments provide evidence that a systematic target discovery is feasible and that the biology of miRNAs can be functionally explored using forward and reverse genetic tools
    Type of Publication: Journal article published
    PubMed ID: 15066187
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  • 26
    Keywords: CANCER ; CANCER CELLS ; CELLS ; EXPRESSION ; CELL ; Germany ; human ; DISEASE ; CDNA ; GENE ; GENE-EXPRESSION ; GENES ; PATIENT ; NF-KAPPA-B ; ACTIVATION ; PHOSPHORYLATION ; treatment ; gene expression ; PCR ; CANCER-CELLS ; PRODUCT ; max ; REGULATOR ; HIGH-LEVEL ; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE ; REDUCTASE ; BIOLOGICAL-ACTIVITIES ; CEREBELLAR NEURONS ; CHROMOSOMAL INSTABILITY ; Fanconi anemia,GAPDH,redox potential,thioredoxin ; REDOX REGULATION
    Abstract: Cancer cells have high levels of thioredoxin ( Trx) and of glyceraldehyde 3- phosphate dehydrogenase ( GAPDH). Cells from patients with the cancer- prone disease Fanconi anemia ( FA) exhibit reduced Trx levels. We found the activity of GAPDH to correlate directly with the endogenous Trx content and mRNA transcripts for GAPDH and TRx reduced in FA cells. The treatment of cells with reduced human Trx stimulated the synthesis of GAPDH mRNA. Similarly, the transfection of cells with an expression plasmid for Trx increased GAPDH mRNA synthesis. Trx treatment of cells and subsequent analysis of the differential gene expression by human cDNA arrays containing about 50 000 different PCR products resulted in more than 300 up- or downregulated genes. Two representative genes, GAPDH and IkappaBalpha/ MAD- 3, were further investigated to confirm their stimulation by Trx. Trx besides being the major carrier of redox potential of cells is also a regulator of gene expression on the transcriptional level. By regulation via Trx, cells are able to adapt to the prevailing redox conditions. These findings also enlighten the pathophysiology of FA in the respect that the characteristic diminution of Trx that results in the dysregulation of gene expression is a basis for the major symptoms of this disease
    Type of Publication: Journal article published
    PubMed ID: 14730345
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  • 27
    Keywords: CANCER ; tumor ; carcinoma ; CLASSIFICATION ; COHORT ; DISTINCT ; GENE ; GENES ; TUMORS ; PATIENT ; prognosis ; treatment ; FREQUENCY ; SUSCEPTIBILITY ; BREAST ; DESIGN ; AGE ; BRCA1 ; OVARIAN-CANCER ; WOMEN ; MUTATION ; REPRODUCIBILITY ; p53 ; MUTATIONS ; MORPHOLOGY ; adenocarcinoma ; CARRIERS ; CANCER-RESEARCH ; SERIES ; POOR-PROGNOSIS ; FEATURES ; BRCA2 GENE ; GRADE ; MUTATION CARRIERS ; GERM-LINE MUTATIONS ; FAMILIAL BREAST-CANCER
    Abstract: Purpose: Germline mutations in the BRCA1 and BRCA2 genes confer increased susceptibility to ovarian cancer. There is evidence that tumors in carriers may exhibit a distinct distribution of pathological features, but previous studies on the pathology of such tumors have been small. Our aim was to evaluate the morphologies and immunophenotypes in a large cohort of patients with familial ovarian cancer.Experimental Design: We performed a systematic review of ovarian tumors from 178 BRCA1 mutation carriers, 29 BRCA2 mutation carriers, and 235 controls with a similar age distribution. Tumors were evaluated by four pathologists blinded to mutation status. Both morphological features and immunochemical staining for p53 and HER2 were evaluated.Results: Tumors in BRCA1 mutation carriers were more likely than tumors in age-matched controls to be invasive serous adenocarcinomas (odds ratio, 1.84; 95% confidence interval, 1.21-2.79) and unlikely to be borderline or mucinous tumors. Tumors in BRCA1 carriers were of higher grade (P 〈 0.0001), had a higher percentage solid component (P 0.001), and were more likely to stain strongly for p53 (P = 0.018). The distribution of pathological features in BRCA2 carriers was similar to that in BRCA1 carriers.Conclusions: Use of pathological features can substantially improve the targeting of predictive genetic testing. Results also suggest that BRCA1 and BRCA2 tumors are relatively. aggressive and may be expected to have poor prognosis, although this may be treatment dependent
    Type of Publication: Journal article published
    PubMed ID: 15073127
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  • 28
    Keywords: CELLS ; EXPRESSION ; carcinoma ; CELL ; Germany ; human ; GENE ; GENE-EXPRESSION ; GENES ; PROTEIN ; PROTEINS ; MOLECULES ; COMPLEX ; COMPLEXES ; KERATINOCYTES ; BOVINE PAPILLOMAVIRUS ; DOWN-REGULATION ; GROWTH-FACTOR RECEPTOR ; papillomavirus ; MOLECULE ; MHC ; TRANSPORT ; IDENTIFICATION ; LESIONS ; gene expression ; DESIGN ; DIFFERENCE ; PLASMA ; MEMBRANE ; STRESS ; SPECTROMETRY ; human papillomavirus ; TYPE-16 ; MASS-SPECTROMETRY ; SURFACE ; CLASS-I ; EPITHELIAL-CELL LINE ; GOLGI-APPARATUS ; HUMAN-PAPILLOMAVIRUS ; MHC class I ; MHC CLASS-I ; CARCINOMAS ; DIFFERENTIAL EXPRESSION ; MEMBRANE PROTEIN ; HaCaT ; MEMBRANE-PROTEIN ; GEL-ELECTROPHORESIS ; MASSES ; E5 PROTEIN ; CERVICAL NEOPLASIA
    Abstract: Membrane proteins differentially expressed in human papillomavirus type 16 (HPV-16) E5-transfected HaCaT cells have been identified. Membrane proteins were isolated and separated by two-dimensional gel electrophoresis. Spots showing quantitative differences between E5-transfected and control cells were extracted and the proteins were identified by nanoelectrospray ionization mass spectrometry. A total of 24 spots was analysed. Among the proteins showing differential expression, a decreased amount of calnexin and increased expression of hsp70, proteins both involved in maturation and transport of MHC class I complexes to the plasma membrane, were noticed. These findings correlate with the decreased surface expression of MHC class I molecules described in E5-expressing cells, HPV-positive cervical lesions and cervical carcinomas. These results stress the value of the proteomic approach, as used here in the experimental design, which allows the correlation of changes in host gene expression with biological functions of viral genes
    Type of Publication: Journal article published
    PubMed ID: 15166425
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  • 29
    Keywords: CANCER ; carcinoma ; CELL ; Germany ; human ; LUNG ; lung cancer ; LUNG-CANCER ; DISEASE ; DISEASES ; HISTORY ; incidence ; RISK ; RISKS ; GENE ; GENES ; PATIENT ; FAMILY ; CARCINOGENESIS ; ASSOCIATION ; POLYMORPHISMS ; NUMBER ; AGE ; family history ; smoking ; SWEDEN ; DATABASE ; HEREDITARY ; HIGH-RISK ; CARCINOGENS ; SIR ; adenocarcinoma ; familial risk ; NATIONWIDE ; squamous cell carcinoma ; TOBACCO ; INDIVIDUALS ; FAMILY-CANCER DATABASE ; familial cancer ; hereditary factors ; lung neoplasms ; YOUNG ; CELL CARCINOMA ; REGISTRY ; SIBLINGS ; AGE 50 ; CARCINOGEN ; SEGREGATION ANALYSIS
    Abstract: The role of hereditary factors in lung cancer is less well understood than in many other human neoplastic diseases. We used a nation-wide family dataset to search for evidence for a genetic predisposition in lung cancer. The Swedish Family-Cancer Database includes all Swedes born in 1932 and later (0- to 68-year-old offspring) with their parents, totaling over 10.2 million individuals. Cancer cases were retrieved from the Swedish Cancer Registry up to year 2000. Standardized incidence ratios (SIR) and 95% confidence limits (Cl) were calculated for age-specific familial risks in offspring by parental or sibling proband, separately. A Kappa test was used to examine the association between familial risk and histology. Compared to the rate of lung cancers among persons without family history, a high risk by parental family history in adenocarcinoma (2.03) and large cell carcinoma (2.14) was found, and only a slightly lower risk was found among patients with squamous cell carcinoma (1.63) and small cell carcinoma (1.55). Among siblings, an increased risk was shown for concordant adenocarcinoma and small cell carcinoma at all ages and for all histological types when cancer was diagnosed before age 50. At young age, risks between siblings were higher than those between offspring and parents. The present data suggest that a large proportion of lung cancers before age 50 years appears to be heritable and probably due to a high-penetrant recessive gene or genes that predispose to tobacco carcinogens; however, this hypothesis needs to be tested in segregation analysis with a large number of pedigrees. (C) 2004 Wiley-Liss. Inc
    Type of Publication: Journal article published
    PubMed ID: 15382071
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  • 30
    Keywords: Germany ; INHIBITION ; GENE ; GENES ; PROTEIN ; PROTEINS ; F
    Type of Publication: Journal article published
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  • 31
    Keywords: CANCER ; EXPRESSION ; tumor ; carcinoma ; CELL ; Germany ; incidence ; GENE ; GENES ; HYBRIDIZATION ; microarray ; cell line ; DIFFERENTIATION ; TISSUE ; LINES ; ACTIVATION ; DNA ; FAMILY ; CELL-LINES ; MEMBER ; MEMBERS ; BREAST-CANCER ; cytokines ; IDENTIFICATION ; AMPLIFICATION ; COMPARATIVE GENOMIC HYBRIDIZATION ; microarrays ; NUMBER ; CHROMOSOMAL-ABERRATIONS ; CELL-LINE ; LINE ; PCR ; REGION ; REGIONS ; adenocarcinoma ; CANCER-RESEARCH ; FREQUENT ; REVEALS ; IMBALANCES ; OVEREXPRESSION ; cell lines ; pancreatic cancer ; pancreatic carcinoma ; GENOMIC HYBRIDIZATION ; HIGH-LEVEL ; CYTOKINE ; ONCOLOGY ; SUBSET ; RE ; PANCREATIC-CANCER ; FAMILIES ; AMPLIFICATIONS ; LEADS ; CANDIDATE GENES ; REAL-TIME ; EGFR ; MALT-LYMPHOMA