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  • CELLS  (19)
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  • 1
    Keywords: TRANSPORT ; prostate cancer ; PROSTATE-CANCER ; bioshuttle ; CANCER-CELLS ; temozolomide ; CANCER ; PEPTIDE ; CELL ; CANCER CELLS ; CELLS ; PROSTATE
    Type of Publication: Proceeding
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  • 2
  • 3
    Keywords: CANCER ; CELLS ; IRRADIATION ; carcinoma ; CELL ; Germany ; THERAPY ; DEATH ; EXPOSURE ; radiation ; DNA ; REDUCTION ; SUFFICIENT ; FLOW ; treatment ; PARTICLES ; CARCINOMA CELLS ; CELL-DEATH ; CERVIX ; DAMAGE ; FRANCE ; BEAM ; bioshuttle ; BORON ; boron neutron capture therapy (BNCT) ; boronophenylalanine (BPA) ; CAPTURE THERAPY ; CARCINOMA-CELLS ; CELLULAR UPTAKE ; DELIVERY ; DNA-DAMAGE ; drug delivery ; LET-effects ; nuclear transport
    Abstract: Boron neutron capture therapy (BNCT) is an experimental treatment modality which depends on a sufficient cellular uptake of Boron (B-10) followed by an exposure to a thermal neutron beam from a. nuclear reactor. High energetic particles (He-4 and Li-7) are. created during the neutron capture reaction and produce DNA damages, which lead to cell killing. Regarding BNCT, the short radiation range of He- and Li-particles is decisive for the distribution of B-10. Until now, BNCT has been lacking for therapeutically effective concentrations of B-10. Twenty-four hours after the combined use of our 'Bioshuttle'-p-borono-phenylalanine(10)-constructs ('Bioshuttle'-p-BPA(10)) and neutron-irradiation, an obvious reduction of the radiation-resistant HeLa-S cells could be observed. No cells were alive 72 h after the incubation with 'Bioshuttle'-p-BPA(10) followed by neutron irradiation. A post-mitotic cell death could be assumed based on flow cytometrical data. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 12832130
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  • 4
    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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  • 5
    Keywords: PEPTIDE ; SPECTRA ; CELLS ; TUMOR-CELLS ; Germany ; THERAPY ; TOXICITY ; SYSTEM ; SYSTEMS ; SITE ; SITES ; TISSUE ; PATIENT ; MECHANISM ; mechanisms ; MOLECULE ; TRANSPORT ; DESIGN ; MEMBRANE ; NUMBER ; DELIVERY ; drug delivery ; MAMMALIAN-CELLS ; THYMIDINE KINASE GENE ; LOCATION ; targeting ; RE ; targeted ; protein transduction ; PHASE ; bioavailability ; ADENOVIRAL VECTORS ; CATION-PI INTERACTIONS ; drug targeting ; MEDIATED GENE-TRANSFER ; nanobiology ; NUCLEIC-ACIDS PNAS ; PENETRATING PEPTIDES ; PHASE-I TRIAL ; site-specific delivery ; THERAPEUTIC APPLICATIONS
    Abstract: Recent advances in the development of diagnostics and therapeutics in the fields of recombinant biochemistry, solid phase peptide synthesis as well as in galenical research have resulted in highly specific and efficient components. Presently, millions of patients can profit from these new therapeutic modalities. The application of an effective anti-tumor dose of drugs can lead to marked toxicity in patients. Therefore, safe and efficient possibilities to transport these compounds to the target are of outmost importance. The importance of drug delivery is pivotal in the wide area of pharmacological research. However, until now, this issue is still to be solved. The main goal of every drug delivery system is the delivery of a precise amount of a drug at a pre-programmed rate to the desired location in order to achieve the necessary drug concentration in the targeted organ for effective treatment. The key problem still remains the achievement of curative doses in a pharmacologically active state in the desired target while avoiding side effects. Although respectable advances can be recognized in this field, the currently applied mechanisms for the transport of therapeutic molecules across biological membranes still remain far from being efficient. Helper molecules could improve delivery to desired target sites. Presently, a number of efforts are made and a huge spectrum of biochemical, biological, medical, pharmaceutical and physical possibilities are arising. However, the design and development of successful therapies based on this technology still remains a great challenge
    Type of Publication: Journal article published
    PubMed ID: 16101505
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  • 6
    Keywords: PEPTIDE ; CELLS ; EXPRESSION ; CELL ; Germany ; THERAPY ; SYSTEM ; TOOL ; GENE ; GENE-EXPRESSION ; GENES ; PROTEIN ; PROTEINS ; transcription ; DNA ; SEQUENCE ; MOLECULE ; TARGET ; TRANSPORT ; gene expression ; EFFICIENT ; MELANOMA ; DELIVERY ; LOCALIZATION ; PEPTIDES ; specificity ; NUCLEAR-LOCALIZATION ; CHEMISTRY ; FEATURES ; RE ; VARIANT ; MELANOMA-CELLS ; REPORTER GENE ; NUCLEAR ; microbiology ; biotechnology ; PLATFORM ; DELIVERY SYSTEMS ; INTERVENTIONS ; NIS
    Abstract: Modern therapeutic approaches without side effects demand substances with features like specificity and effectiveness. Our solution is a safe and efficient transfer procedure of pharmaceutics or diagnostics into cells. We developed a transport system and tested both a variant for transporting plasmid-DNA as a bicistronic reporter molecule as well as a variant for control of gene expression like the tyrosinase gene in melanoma cells. Clamp-PNAs were investigated in gene expression control with this tyrosinase gene. Our peptide-based BioShuttle transfer system also contains a nuclear localization sequence realizing the delivery of our plasmid phNIS-IRES-EGFP coding for the two independent reporter genes, namely the two reporter proteins Sodium Import Symporter (NIS) and Enhanced Green Fluorescent Protein (EGFP). With their expression we confirmed the potential of the BioShuttle as a suitable and variable delivery platform and as appropriate tool for an anti-genetic transcription tyrosinase control in melanoma cells
    Type of Publication: Journal article published
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  • 7
    Keywords: CELLS ; Germany ; SYSTEM ; SYSTEMS ; DEATH ; PROTEIN ; PROTEINS ; DNA ; MECHANISM ; mechanisms ; CELL-DEATH ; inactivation ; MELANOMA ; skin tumors ; OXYGEN ; SCIENCE ; ROS ; FLUORESCENT PROTEIN ; fluorescent proteins ; METAL-IONS ; Carrier Molecules ; Photo-dynamic therapy (PDT)
    Abstract: Inactive compounds like autofluorescent proteins can absorb visible daylight (around 500-700 nm) and can emit active electrons producing reactive oxygen species (ROS) leading to an increase in photokilling processes in bacteria The endogenously originated ROS create single strand breaks in the cells DNA. These various types of breaks can be partially repaired by different cellular repair systems but a high number of breaks leads to cell death A dramatic increase in cell killing can be observed from green, via yellow to red color emission This was tested by colony forming ability. The generation of ROS and the bacterial protection mechanisms are discussed. We outline sonic possibilities for use the protein's properties for treatment of antibiotic multi-resistant and difficult to treat bacteria like the methicillin-resistant Staphylococcus aureus (MRSA) (C) 2009 Elsevier B V All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 20042344
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  • 8
    Keywords: RECEPTOR ; CANCER ; CELLS ; IRRADIATION ; radiotherapy ; tumor ; AGENTS ; CELL ; Germany ; human ; INHIBITION ; THERAPY ; TOXICITY ; VISUALIZATION ; DISEASE ; GENE ; GENES ; HYBRIDIZATION ; PROTEIN ; transcription ; METABOLISM ; TISSUE ; TUMORS ; radiation ; TRANSDUCTION ; NF-KAPPA-B ; ACTIVATION ; MECHANISM ; prognosis ; TISSUES ; mechanisms ; DOWN-REGULATION ; SEQUENCE ; SEQUENCES ; signal transduction ; SUPPRESSION ; SIGNAL ; BREAST ; breast cancer ; BREAST-CANCER ; RADIATION-THERAPY ; gene expression ; PROSTATE-CANCER ; SIGNAL-TRANSDUCTION ; COMPONENT ; CELL-CYCLE CONTROL ; IN-SITU HYBRIDIZATION ; DATABASE ; DNA-DAMAGE ; NORMAL TISSUE ; ALPHA-TOCOPHEROL ; RE ; INCREASE ; GLIOMA ; ARRAY ; HELA-CELLS ; LEVEL ; analysis ; EVENTS ; function ; PROTEOLYSIS ; clinical study ; GAMMA-RAYS ; PREFERENTIAL RADIOSENSITIZATION ; PTX-treatment ; UDP-GLUCOSE DEHYDROGENASE
    Abstract: Aim in cancer therapy is to increase the therapeutic ratio eliminating the disease while minimizing toxicity to normal tissues. Radiation therapy is a main component in targeting cancer. Radiosensitizing agents like pentoxyphylline (PTX) have been evaluated to improve radiotherapy. Commonly, cells respond to radiation by the activation of specific early and late response genes as well as by inhibition of genes, which are expressed under normal conditions. A display of the genetic distinctions at the level of transcription is given here to characterize the molecular events underlying the radiosensitizing mechanisms. The method of suppression subtractive hybridization allows the visualization of both induced and repressed genes in irradiated cells compared with cells sensitized immediately after irradiation. The genes were isolated by cDNA-cloning, differential analysis and sequence similarity search. Genes involved in protein synthesis, metabolism, proteolysis and transcriptional regulation were detected. It is important that genes like KIAA280, which were only known as unidentified EST sequences before without function, but inaccessible by array technology were recovered as functional genes. Database searches for PTX-induced genes detected a human mRNA completely unknown. In case of suppressed genes, we detected several mRNAs; one thereof shows homology to a hypothetical protein possibly involved in signal transduction. A further mRNA encodes the protein BM036 supposed to associate with the E2F transcription factor. A hypothetical protein H41 was detected, which may repress the Her-2/neu receptor influencing breast cancer, gliomas and prostate tumors. Radiation combined with PTX may lead to a better prognosis by down regulation of the Her-2/neu, which will be proven by clinical studies in the near future. (c) 2006 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 17192923
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  • 9
    Keywords: PEPTIDE ; CELLS ; INHIBITOR ; CELL ; human ; LUNG ; LYMPHOCYTES ; DELIVERY ; ASSEMBLIES ; assembly
    Type of Publication: Journal article published
    PubMed ID: 18695744
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  • 10
    Keywords: CANCER ; CANCER CELLS ; CELLS ; IN-VITRO ; tumor ; CELL ; Germany ; PHASE-I ; PROSTATE ; THERAPY ; VITRO ; SYSTEMS ; MOLECULES ; TUMORS ; PATIENT ; prognosis ; RADIATION-THERAPY ; VECTORS ; prostate cancer ; PROSTATE-CANCER ; RATES ; chemotherapy ; CANCER-CELLS ; bioshuttle ; DELIVERY ; NUCLEUS ; PEPTIDES ; GENE-THERAPY ; ADJUVANT ; AGENT ; CHEMISTRY ; THERAPIES ; radiation therapy ; ANTITUMOR IMIDAZOTETRAZINES ; temozolomide ; INTERVENTIONS ; chemoselective ligation ; inverse Diels-Alder reaction ; RESPONSE RATES
    Abstract: Hormone-refractory prostate cancer (HRPC), Insensitive to most cytostatic interventions, features low response rates and bad prognosis. Studies with HRPC treated with temozolomide (TMZ) showed a poor response and the results were discouraging. Therefore, TMZ has been considered to be Ineffective for the treatment of patients with symptomatic and progressive HRPC. A solution to this problem is demonstrated in this study by combining proper solid-phase peptide synthesis and a chemoselective new 'click' chemistry based on the Diels-Alder reaction with 'Inverse-electron-demand'(DAR(inv)) for the construction of a highly efficient TMZ-BioShuttle in which TMZ is ligated to transporter and subcellular address molecules. The transport to the targeted nuclei resulted in much higher efficiency and better pharmacological effects. The reformulation of TMZ to TMZ-BloShuttle achieved higher in vitro killing of prostate cancer cells. Accordingly, the potential of TMZ for the treatment of prostate tumors was dramatically enhanced even in a tenfold lower concentration than applied normally. This TMZ-BioShuttle may be well suited for combining chemotherapy with other cytostatic agents or radiation therapy. Copyright (K) 2009 European Peptide Society and John Wiley & Sons, Ltd
    Type of Publication: Journal article published
    PubMed ID: 19177421
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