Your email was sent successfully. Check your inbox.

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

Proceed reservation?

Export
Filter
Collection
Keywords
  • 1
    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
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: CANCER ; human ; MODEL ; MODELS ; DNA adducts ; SITE ; SITES ; ENZYMES ; TISSUE ; RESOLUTION ; ACTIVATION ; LIGAND ; DNA ; REDUCTION ; DNA ADDUCT FORMATION ; TISSUES ; BINDING ; ACID ; PATTERNS ; HUMANS ; ASSAY ; ACTIVE-SITE ; DNA-BINDING ; METABOLIC-ACTIVATION ; ADDUCTS ; ORIENTATION ; BINDS ; aristolochic acid ; BALKAN ENDEMIC NEPHROPATHY ; CHINESE HERBS NEPHROPATHY ; P-32 POSTLABELING ANALYSIS ; DNA-ADDUCTS ; RECOMBINANT ; CRYSTALLOGRAPHIC STRUCTURE ; urothelial cancer ; CARCINOGEN ; REDUCTASE ; interaction ; development ; IRON ; ADDUCT ; ENZYME ; DNA ADDUCT ; P-32-postlabeling ; docking ; human cytochromes P450 ; computer modeling ; cytochromes P450 1A1 and 1A2 ; DNA binding ; NADPH ; reductive activation
    Abstract: Aristolochic acid (AA), a naturally occurring nephrotoxin and carcinogen, has been associated with the development of urothelial cancer in humans. Using the P-32-postlabeling assay we showed that AAI is activated by human recombinant cytochrome P450 (CYP) 1A1, CYPIA2 and NADPH:CYP reductase to species generating DNA adduct patterns reproducing those found in renal tissues from humans exposed to AA. 7-(Deoxyadenosin-N-6-yl)aristolactam I, 7-(deoxyguanosin-N-2-yl) aristolactam I and 7-(deoxyadenosin-N-6-yl)aristolactam II were identified as AA-DNA adducts formed from AAI by the enzymes. The formation of these AA-derived DNA adducts indicates that all the human enzymes reduce the nitro group of AAI to the putative reactive cyclic nitrenium ion responsible for adduct formation. The concentrations of AAI required for its half-maximum DNA binding were 38,65 and 126 mu M AAI for reductive activation by human CYP1A2, CYP1A1 and NADPH:CYP reductase, respectively. CYP1A1 and 1A2 homology modeling followed by docking of AAI to the CYP1A1 and 1A2 active centers was utilized to explain the potential of these enzymes to reduce AAI. Models of human CYP1A1 and 1A2 were constructed on the basis of the crystallographic structure of truncated mammalian CYP enzymes, CYP2B4, 2C5, 2C8, 2C9 and 3A4. The in silico docking of AAI to the active sites of CYP1A1I and 1A2 indicates that AAI binds as an axial ligand of the heme iron and that the nitro group of AAI is in close vicinity to the heme iron of CYPIA2 in an orientation allowing the efficient reduction of this group observed experimentally. The orientation of AAI in the active centre of CYP1A1 however causes an interaction of the heme iron with both the nitro- and the carboxylic groups of AAI. This observation explains the lower reductive potential of CYP1A1 for AAI than CYP1A2, detected experimentally. (c) 2005 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 16125300
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: CANCER ; SURVIVAL ; DISEASE ; SURGERY ; CARCINOGENESIS ; STAGE ; AMPLIFICATION ; AGE ; PHENOTYPE ; PROGNOSTIC-SIGNIFICANCE ; neuroblastoma ; N-MYC ; analysis ; JAPANESE ; multivariate analysis ; NMYC
    Abstract: The CpG island methylator phenotype (CIMP) was closely associated with poor overall survival (OS) in Japanese neuroblastoma (NBL) cases in our previous study. Here, in German NBL cases, CIMP(+) cases (n=95) showed markedly poorer OS (hazard ratio (HR)=9.5; P〈0.0001) and disease-free survival (DFS) (HR=5.4; P〈0.0001) than CIMP(-) cases (n=50). All the 23 cases with N-myc amplification had CIMP. Among the remaining cases without N-myc amplification, CIMP(+) cases (n=27) had a poorer OS (HR=4.5; P=0.02) and DFS (HR=5.2; P〈0.0001) than CIMP(-) cases (n=95). In multivariate analysis, CIMP and N-myc amplification had an influence on OS and DFS independent of age and disease stage. CIMP had a stronger influence on DFS than N-myc amplification while N-myc had a stronger influence on OS
    Type of Publication: Journal article published
    PubMed ID: 16759796
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: RECEPTOR ; ANGIOGENESIS ; CANCER ; CANCER CELLS ; CELLS ; EXPRESSION ; GROWTH ; tumor ; TUMOR-CELLS ; carcinoma ; ENDOTHELIAL GROWTH-FACTOR ; Germany ; human ; PATHWAY ; SYSTEM ; PROTEIN ; TISSUE ; TUMORS ; LINES ; PATIENT ; COMPLEX ; COMPLEXES ; MARKER ; prognosis ; TISSUES ; BINDING ; CELL-LINES ; SIGNAL ; NERVOUS-SYSTEM ; PROGRESSION ; ovarian cancer ; OVARIAN-CANCER ; CELL-LINE ; FUSION ; LINE ; CANCER-CELLS ; ADHESION ; INTEGRIN ; CARCINOMAS ; RT-PCR ; L1 ; NEURITE OUTGROWTH ; ADHESION MOLECULE ; L1 adhesion molecule ; ovarian carcinoma ; OVEREXPRESSION ; cell lines ; TUMOR CELLS ; PERMEABILITY ; RE ; TUMOR-GROWTH ; cell adhesion ; LEVEL ; TUMOR-CELL ; ADHESION MOLECULE L1 ; OVARIAN CARCINOMAS ; function ; SIGNALS ; OVARIAN ; VARIETIES ; VASCULAR-PERMEABILITY ; heterophilic binding ; mesothelial cells ; MOUSE LEUKOCYTES ; neuropilin-1 ; SEMAPHORIN-III
    Abstract: The progression of ovarian cancer is driven by a variety of cellular factors that are incompletely understood. Binding of tumor cells to normal cells and to soluble factors influence tumor growth, angiogenesis and the stimulation of vascular permeability leading to ascites production. L1 adhesion molecule is overexpressed in ovarian carcinoma and is associated with bad prognosis. One receptor for L1 is Neuropilin-1 (NRP-1) that is also known as a receptor for VEGF(165). In the nervous system a complex of NRP-1 and L1 transmits signals by the neurorepellant Sem3A that is critical for the control of neurite outgrowth. NRP-1 has also been detected in human carcinomas but its function remains unknown. Here, we have examined NRP-1 expression in ovarian carcinoma cell lines and tissue. We report that little NRP-1 protein was detected in primary ovarian carcinoma tissues or established cell lines although mRNA for soluble and transmembrane NRP-1 were detected by RT-PCR. Instead, we observed strong expression of NRP-1 in mesothelial cells, which form the lining of the peritoneum. NRP-1 could serve as an isolation marker for primary mesothelial cells present in ascites fluid. We demonstrate that ovarian cancer cells expressing L1 can bind to NRP-1 overexpressing cells and mesothelial cells. Likewise, soluble L1 isolated from ascites of patients or produced as a fusion protein could bind to NRP-1 overexpressing cells and a direct interaction was demonstrated at the protein level. These findings suggest that L1 can support the binding of ovarian carcinoma cells to mesothelial cells via NRP-1. The L1-NRP-1 binding pathway could contribute to the growth of ovarian carcinomas and to reciprocal signalling between mesothelial cells and tumors. (c) 2005 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 16377081
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Keywords: CANCER ; EXPRESSION ; tumor ; Germany ; human ; POPULATION ; SITE ; GENE ; MOLECULAR CHARACTERIZATION ; DNA ; NERVOUS-SYSTEM ; HOMOZYGOUS DELETIONS ; CANCER-CELLS ; REGIONS ; MUTATIONS ; gene amplification ; common fragile sites ; RENAL-CELL CARCINOMA ; CHROMOSOMES ; DISORDERS ; RE ; PREFERENTIAL INTEGRATION ; function ; fragile sites ; FRA13A ; HUMAN-CHROMOSOME 7 ; NBEA ; neurobeachin ; RECESSIVE JUVENILE PARKINSONISM ; DELTA-2 GLUTAMATE-RECEPTOR ; neuropsychiatric disorders ; TRINUCLEOTIDE REPEAT
    Abstract: Common fragile sites are unstable chromosomal regions that predispose chromosomes to breakage and rearrangements Recombinogenic DNA sequences encompassing these sites may contribute to both germinal and somatic genomic mutations, and the genomic instability at these regions might cause severe inherited disorders or predispose to cancer. In this review, we discuss the characterization of common fragile site FRA13A within the neurobeachin gene, which is involved in development and function of the central nervous system. We raise the possibility of an implication of common fragile sites in neuropsychiatric disorders and overview previous and recent reports concerning individual variability of expression of common fragile sites in human populations. (c) 2005 Published by Elsevier Ireland Ltd
    Type of Publication: Journal article published
    PubMed ID: 16298041
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Keywords: APOPTOSIS ; CANCER ; CELLS ; EXPRESSION ; GROWTH ; carcinoma ; CELL ; Germany ; INHIBITION ; THERAPY ; HEPATOCELLULAR-CARCINOMA ; PROTEIN ; TISSUE ; LINES ; MICE ; PATIENT ; IMPACT ; INDUCTION ; CELL-LINES ; treatment ; hepatocellular carcinoma ; resistance ; AGE ; metastases ; NUDE-MICE ; CELL-LINE ; chemotherapy ; leukemia ; LINE ; MODULATION ; p53 ; CANCER-PATIENTS ; CARCINOMAS ; CISPLATIN ; CANCER PATIENTS ; cell lines ; CANCER-THERAPY ; protein expression ; P53 STATUS ; GEMCITABINE ; RE ; cancer therapy ; GENDER ; dexamethasone ; GLUCOCORTICOID-INDUCED APOPTOSIS ; NAUSEA ; HISTOLOGY ; corticosteroids ; GLUCOCORTICOIDS ; correlation ; GAMMA-IRRADIATION ; viability ; 5-FU ; xenograft
    Abstract: The glucocorticoid dexamethasone is frequently used as co-treatment in cytotoxic cancer therapy, e.g. to prevent nausea, to protect normal tissue or for other reasons. While the potent pro-apoptotic properties and the supportive effects of glucocorticoids to tumour therapy in lymphoid cells are well studied, the impact to cytotoxic treatment of colorectal and hepatocellular carcinoma is unknown. We tested apoptosis-induction, viability, tumour growth and protein expression using 8 established cell lines, 18 surgical specimen and a xenograft on nude mice. In the presence of dexamethasone we found strong inhibition of apoptosis in response to 5-FU, cisplatin, gemcitabine or gamma-irradiation, enhanced viability and tumour growth of colorectal and hepatocellular carcinomas. No correlation with age, gender, histology, TNM, the p53 status and induction of therapy resistance by dexamethasone cotreatment could be detected. These data show that glucocorticoid-induced resistance occurs not occasionally but is common in colorectal and hepatocellular carcinomas implicating that the use of glucocorticoids may be harmful for cancer patients. (c) 2005 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 16338063
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Keywords: CANCER ; CELLS ; EXPRESSION ; carcinoma ; Germany ; SITE ; GENES ; PROTEIN ; PROTEINS ; TISSUE ; CARCINOGENESIS ; PHOSPHORYLATION ; antibodies ; MOUSE ; LESIONS ; PROGRESSION ; immunohistochemistry ; CERVIX ; CELL-LINE ; REGION ; REGIONS ; CARCINOMAS ; INTERCELLULAR COMMUNICATION ; STRATIFIED EPITHELIUM ; JUNCTION ; premalignant ; gap junction ; cell communication
    Abstract: Connexins are proteins that form the connexons, gap junction structures, which allow cells to communicate. Phosphorylation of connexins has been found to impair this communication. Using an antibody specifically recognizing the S279/S282-phosphorylated form of connexin43 (Cx43) for immunohistochemistry, we have analysed Cx43 phosphorylation in normal epithelium, CIN III lesions, and carcinomas of the cervix. We found that in normal epithelium the basal layer was devoid of staining and most of the protein was localized in stratum spinosum and stratum granulosum. In pre-malignant CIN-III lesions Cx43 was strongly phosphorylated, but the basal layer was still negative. In squamous carcinomas, the cells were intensely stained. In these tumours, sites of strong staining were adjacent to less stained regions, suggesting that the tumours are intrinsically heterogeneous. Immunoblotting of proteins extracted from carcinomas with the specific antibody showed the classical pattern of multiple reacting bands, with the appearance of low migrating forms of the protein. Our results suggest that increased S279/S282 phosphorylation of Cx43 is the result of altered tissue structure rather than of cell malignization. (c) 2005 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 15958277
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Keywords: RECEPTOR ; CANCER ; EXPRESSION ; GROWTH ; GROWTH-FACTOR ; tumor ; CELL ; human ; GENE ; GENE-EXPRESSION ; cell line ; TUMORS ; MECHANISM ; IMPACT ; primary ; REDUCTION ; TRANSACTIVATOR ; BREAST ; breast cancer ; BREAST-CANCER ; TARGET ; CHROMATIN ; gene expression ; ASSAY ; VECTOR ; PROMOTER ; BRCA1 ; ovarian cancer ; OVARIAN-CANCER ; WOMEN ; MUTATION ; CELL-LINE ; LINE ; MUTATIONS ; CARRIERS ; FACTOR-I ; ONCOLOGY ; MUTATION CARRIERS ; interaction ; GROWTH-FACTOR-I ; Sp1 ; LEVEL ; analysis ; TRANSCRIPTIONAL ACTIVATION ; ASSAYS ; BREAST-TUMORS ; IMMUNOHISTOCHEMICAL ANALYSIS ; EVALUATE ; FAMILIAL BREAST ; OVARIAN ; FACTOR SYSTEM ; SUBSTRATE-1 EXPRESSION ; mechanism of action ; GROWTH-FACTORS ; insulin-like growth factor-I ; NONCARRIERS ; IGF ; IGF-I receptor ; ASHKENAZI ; EARLY-ONSET BREAST ; IGFs ; insulin-like growth factor-I (IGF-I) ; SUSCEPTIBILITY GENE BRCA1
    Abstract: The insulin-like growth factors (IGFs) play a pivotal role in breast cancer. Inherited predisposition to breast and ovarian cancer is associated with germline BRCA1/BRCA2 mutations. To evaluate the impact of BRCA1 mutations on IGF-IR gene expression, we performed an immunohistochemical analysis of IGF-IR in primary breast tumors from BRCA1 mutation carriers and non-carriers. Results obtained revealed a significant elevation in IGF-IR levels in tumors from BRCA1 mutation carriers compared with non-carriers. To assess the potential inhibitory role of BRCA1 on IGF-IR levels, we infected the BRCA1-deficient HCC1937 cell line with a BRCA1-encoding adenoviral vector. Results of Western blots showed that BRCA1 induced a large reduction in endogenous IGF-IR levels. Furthermore, results of chromatin immunoprecipitation assays indicated that the mechanism of action of BRCA1 involves interaction with Sp1, a potent transactivator of the IGF-IR gene. In conclusion, our data suggests that the IGF-IR gene is a physiologically relevant downstream target for BRCA1 action. (C) 2007 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 17766039
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Keywords: CANCER ; CELLS ; GROWTH ; IN-VITRO ; INHIBITOR ; SURVIVAL ; tumor ; CELL ; Germany ; VITRO ; GENE-EXPRESSION ; PROTEIN ; PROTEINS ; DIFFERENTIATION ; ACTIVATION ; primary ; CELL-LINES ; ANTITUMOR-ACTIVITY ; culture ; ACID ; RATES ; CELL-LINE ; acetylation ; HIGH-RISK ; HISTONE DEACETYLASE ; Ras ; retinoids ; neuroblastoma ; N-MYC ; ONCOLOGY ; RE ; TUMOR-SUPPRESSOR ; LEVEL ; HISTONE DEACETYLASE INHIBITORS ; SUPPRESSOR ; SODIUM VALPROATE ; retinoblastoma ; tumor suppressor ; HC-TOXIN ; RB tumor suppressor network ; E2F-1 ; HIGH-RISK NEUROBLASTOMA ; SUPPRESSES
    Abstract: Treatment of high-risk neuroblastoma (NB) is difficult. Novel therapeutics improving survival rates are urgently required. We have previously shown that the histone deacetylase inhibitor (HDACI) Helminthosporium carbonum (HC)toxin induces differentiation of neuroblastoma (NB) cells. Here, we show that HC-toxin inhibits the growth of both established NB cell lines and primary cultures with and without amplified MYCN stronger than retinoids (RAs) and other HDACIs (MS-275, n-butyric acid, suberoylanilide hydroxamic acid, trichostatin A, valproic acid). Nanomolar dosages suppress E2F-1, N-myc, Skp2, Mad2 and survivin proteins, found at high levels in high-risk NBs, more efficiently than both RAs and other HDACIs. The level of hypophosphorylated active retinoblastoma (RB) tumor suppressor protein is increased most effectively. HC-toxin's epoxy group is essential for inhibiting HDACs and promoting anti-NB activity. Without this functional group, those cellular effects are not observed. In conclusion, the anti-NB activity of HC-toxin is superior to that of RAs and that of all other HDACIs tested. (C) 2008 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 18262346
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    Keywords: 3-nitrobenzanthrone, 7,12-Dimethylbenz[a]anthracene, ADDUCTS, air pollution, Application, CANCER, CA
    Abstract: 3-Nitrobenzanthrone (3-NBA), a genotoxic mutagen found in diesel exhaust and ambient air pollution and its active metabolite N-hydroxy-3-aminobenzanthrone (N-OH-3-ABA) were tested for initiating and complete carcinogenic activity in the NMRI mouse skin carcinogenesis model. Both compounds were found to be inactive as either tumour initiators or complete carcinogens in mouse skin over a dose range of 25-400 nmol. Topical application of 3-NBA and N-OH-3-ABA produced DNA adduct patterns in epidermis, detected by P-32-postlabelling, similar to those found previously in other organs of rats and mice. 24 h after a single treatment of 100 nmol DNA adduct levels produced by 3-NBA (18 +/- 4 adducts/10(8) nucleotides) were 6 times lower than those by 7,12-dimethylbenz[a]anthracene (DMBA; 114 +/- 37 adducts/10(8) nucleotides). In contrast, identical treatment with N-OH-3-ABA resulted in adduct levels in the same range as with DMBA (136 +/- 25 adducts/10(8) nucleotides), indicating that initial DNA adduct levels do not parallel tumour initiating activity. When compounds were tested for tumour initiating activity by a single treatment followed by twice-weekly applications of TPA. DNA adducts formed by DMBA, but not by 3-NBA or N-OH-3-ABA, were still detectable 40 weeks after treatment. When tested for activity as complete carcinogens by twice-weekly topical application, 3-NBA and N-OH-3-ABA produced identical DNA adduct profiles in mouse skin, with adducts still detectable after 40 weeks. Only 3-NBA produced detectable adducts in other organs. (C) 2009 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 19442433
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...