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  • 1
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  79. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie; 20080430-20080504; Bonn; DOC08hnod173 /20080422/
    Publication Date: 2008-04-21
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 2
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  78. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e.V.; 20070516-20070520; München; DOC07hnod447 /20070424/
    Publication Date: 2007-04-24
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 3
    Keywords: CANCER ; IN-VITRO ; tumor ; CELL ; COMBINATION ; Germany ; human ; THERAPY ; VIVO ; DRUG ; TUMORS ; SURGERY ; radiation ; PATIENT ; MALIGNANCIES ; chemotherapy ; SQUAMOUS-CELL CARCINOMA ; HEAD ; CROSS-RESISTANCE ; NECK ; ARTIFACTS ; head and neck ; ELIMINATION ; MANAGEMENT ; NECK-CANCER ; INDUCTION CHEMOTHERAPY ; MALIGNANCY ; PROGRAM ; review ; head and neck cancer ; THERAPIES ; ORGAN PRESERVATION ; ADVANCED LARYNGEAL-CANCER ; DRUG-RESPONSE ASSAY ; SENSITIVITY ASSAYS ; chemosensitivity ; EX-VIVO ; chemosensitivity assays ; COLONY-FORMING ASSAY ; predictive tests ; SOFT-AGAR ; SOLID TUMORS
    Abstract: Despite many advances in predictive testing of human malignancies, we are far from using it routinely in clinical practice. Investigating the responsiveness of solid tumors to cytostatic drugs is particularly challenging. Nevertheless, for head and neck cancer, chemosensitivity testing is an increasingly attractive option, since chemotherapy has proven to have curative potential in the therapy of head and neck cancer, in particular in combination with radiation. The significant need for predictive methods to identify patients responsive to therapy, first of all in organ preservation programs, which is an alternative to first-line surgery, had recently renewed the discussion on a possible role of chemosensitivity testing in head and neck cancer. In this review, we discuss the current state of chemosensitivity testing in head and neck cancer. Recent methodological developments, in particular elimination of photochemical artifacts and inclusion of stromal cell response studies, may soon augment the value of ex vivo chemosensitivity testing for the management of head and neck cancer
    Type of Publication: Journal article published
    PubMed ID: 15249723
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  • 4
    Keywords: CANCER ; Germany ; THERAPY ; TOOL ; MOLECULES ; MOLECULE ; PRODUCT ; PEPTIDES ; GLUCOSE ; GLYCOSIDES ; CLUSTER ; BRAIN-TUMORS ; BNCT ; boron,boron neutron capture therapy,carboranes,drug research,imaging agents
    Abstract: The synthesis of a new ortho-carborane derivative, tetracarboranylketone 4, is reported here. Ketone 4 was prepared from a tetraalkynylated ketone by the addition of decaborane. The keto group was then easily modified to yield the glycosides 17alpha and 18beta, which contain glucose or galactose, respectively, and the nucleotide 13b. In addition to ketone 4, which is acyclic, cyclic ketone 8 was also synthesised. X-ray diffraction analysis of compound 4 indicated the presence of two toluene guest molecules per molecule of the host compound. Furthermore, compound 4 displays a rather low cytotoxicity. These novel products can be used as building blocks to create a new class, of biomolecules containing high-density carborane clusters. Such molecules, may constitute powerful tools for applications like Boron Neutron Capture Therapy or Energy-Filtering Transmission Electron Microscopy
    Type of Publication: Journal article published
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  • 5
    Keywords: CANCER ; CELLS ; tumor ; carcinoma ; Germany ; THERAPY ; TUMORS ; PATIENT ; treatment ; 5-FLUOROURACIL ; ASSAY ; chemotherapy ; EPITHELIAL-CELLS ; HEAD ; NECK ; squamous cell carcinoma ; PREDICTION ; sensitivity ; head and neck carcinoma ; HNSCC ; INFUSION ; SOLID TUMORS ; COLONY FORMATION ; chemosensitivity testing ; head and neck squamous cell carcinoma ; SPECIMENS ; 5-FU ; drug combinations ; tumor stroma
    Abstract: Previous studies focusing on response prediction to chemotherapy by chemosensitivity testing of tumor explants has focused on the response determination of single cytostatic drugs, in contrast to the common clinical application of cytostatic drug combinations. Therefore, the present study was aimed at determining the quantitative ex vivo chemoreactivity of epithelial cells from head and neck squamous cell carcinoma (HNSCC) specimens to cytostatic drug combinations. Specimens from 12 histologically-confirmed HNSCC were investigated. According to a previously established ex vivo colony formation assay, the individual cellular chemoreactivity was determined quantitatively for combinations of 4 cytostatic drugs: cis-platinum (cis-DDP), carboplatin (CBDCA), 5-Fluorouracil (5-FU) and docetaxel (DTX). The tests were performed using drug combinations according to recent clinical therapy regimens in the treatment of solid tumors: i) cis-DDP + 5FU, ii) CBDCA + 5FU, iii) cis-DDP + DTX and iv) CBDCA + DTX The approach provides individual drug response patterns of epithelial as well as of stromal cells. Individual, selective sensitivities were found for each drug combination tested. The stromal and epithelial chemoreactivity profiles differed in most of the specimens. Moreover, stromal cell chemoresistance dominated selective epithelial chemosensitivities in the majority of cases. The determination of the epithelial ex vivo chemoreactivity identified individual chemosensitivities which were verified by the clinical history of the patient. Therefore, the described protocol to determine the ex vivo chemoresponse of HNSCC specimens to cytostatic drug combinations may help to provide clinicaly useful information concerning the individual chemoresponse of HNSCC with regard to individualization of oncological decision making
    Type of Publication: Journal article published
    PubMed ID: 16619587
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  • 6
    Keywords: carcinoma ; Germany ; VIVO ; SITE ; SITES ; PATIENT ; culture ; TRIAL ; LESIONS ; ASSAY ; chemotherapy ; HEAD ; NECK ; squamous cell carcinoma ; sensitivity ; CISPLATIN ; MULTICENTER ; PHASE-II ; CELL CARCINOMA ; GEMCITABINE ; ORGAN PRESERVATION ; ADVANCED LARYNGEAL-CANCER ; head and neck carcinoma ; HNSCC ; head and neck squamous cell carcinoma ; SPECIMENS ; predictive testing ; RECURRENT HEAD ; vinca alkaloids ; vinorelbine
    Abstract: Background: Vinorelbine has been identified as an effective cytostatic drug in head and neck squamous cell carcinoma (HNSCC). To predict the individual chemo-response, the application of an ex vivo assay to quantify the response of HNSCC to vinorelbine is presented. Patients and Methods: Twelve biopsies from primary HNSCC sites and five biopsies from metastatic lesions were analyzed (n=17). The specimens were investigated ex vivo for the overall, epithelial and stromal chemoresponse to vinorelbine. Results: By selective evaluation of the epithelial chemoresponse, the applied assay identified three specimens as vinorelbine-sensitive (18%), including one de novo sensitivity in a metastatic lesion of a vinorelbine-resistant hypopharyngeal carcinoma. Conclusion: Applying flavin protecting culture methods and with careful correction for the stromal cell effect, the assay generated reliable data for the assessment of the individual chemoresponse of HNSCC specimens to vinorelbine. The assay may, therefore, facilitate the implementation of individualized chemotherapy protocols
    Type of Publication: Journal article published
    PubMed ID: 16821617
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  • 7
    Keywords: CELLS ; GROWTH ; CELL ; Germany ; DRUG ; SERA ; mechanisms ; culture ; EFFICACY ; PRODUCT ; VARIABILITY ; CYTOTOXICITY ; METHOTREXATE ; GROWTH ARREST ; ARREST ; SERUM ; ONCOLOGY ; RE ; PRODUCTS ; LEVEL ; methods ; TESTS ; BOVINE ; KB cells ; DRUGS ; ANTITUMOR ACTIVITIES ; MEDIA ; antifolate resistance ; antifolate salvage ; CCRF-CEM cells ; FBS gold ; FCS gold ; fetal bovine serum ; LY231514
    Abstract: Background: Batch variability of sera used for cell culture is of considerable experimental concern. A novel fetal calf serum product, FCS Gold, was claimed to be the first defined fetal calf serum free of batch variation. Materials and Methods: The efficacy of methotrexate (MTX) and LY231514 (multitargeted antifolate, MTA) in CCRF-CEM cells and KB cells was compared using media supplemented with FCS Gold or conventional fetal bovine serum. Results: IC50 values from tests using conventional serum corresponded to published data. FCS Gold fully protected the cells from antifolate drug cytotoxicity. Dialysis of FCS Gold restored responsiveness to antifolate drugs. Elevated levels of hypoxanthine and thymidine were present in FCS Gold. They were approximately 10-fold greater than the concentrations required to overcome growth arrest mediated by 2 mu M MTX. Conclusion: FCS Gold or identical products, e.g. FBS Gold, should not be used in studies on antifolate drug action
    Type of Publication: Journal article published
    PubMed ID: 17465201
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  • 8
    Keywords: CELLS ; IN-VITRO ; tumor ; carcinoma ; CELL ; evaluation ; Germany ; LUNG ; VIVO ; GENERATION ; INFORMATION ; TUMORS ; PATIENT ; IMPACT ; 5-FLUOROURACIL ; ASSAY ; resistance ; HEAD ; NECK ; squamous cell carcinoma ; GREECE ; head and neck ; MULTIDRUG-RESISTANCE ; INDUCTION CHEMOTHERAPY ; CELL CARCINOMA ; ORGAN PRESERVATION ; ADVANCED LARYNGEAL-CANCER ; DRUG-RESPONSE ASSAY ; head and neck carcinoma,HNSCC,chemosensitivity testing,tumor stroma,ex vivo culture ; P-GLYCOPROTEIN ; PROGNOSTIC IMPACT ; SENSITIVITY ASSAYS ; TUMOR VOLUME
    Abstract: Background: Reliable chemosensitivity testing of head and neck squamous cell carcinoma (HNSCC) still faces methodical limitations. Since stromal cell contamination has been found to preclude reliable radiosensitivity testing of HNSCC as well as chemosensitivity testing of lung tumors, the present study investigates the impact of stromal cell contamination on chemosensitivity testing of HNSCC Patients and Methods: Seventeen biopsies from HNSCC were analyzed The specimens were investigated using an ex vivo colony formation assay which allows for the quantitative and separate determination of the overall, as well as the epithelial, and stromal response to carboplatin, 5-fluorouracil and docetaxel. Results: The overall chemoresponse was dominated by stromal cell multidrug resistance. However, by selective evaluation of the epithelial chemoresponse, individual chemosensitivity patterns could be identified Conclusion: Multidrug-resistant stromal cells preclude the reliable assessment of the chemoresponse of HNSCC specimens. Careful correction for stromal cell effects is a prerequisite for the generation of therapeutically useful information
    Type of Publication: Journal article published
    PubMed ID: 15015616
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  • 9
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    German Medical Science; Düsseldorf, Köln
    In:  77. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e.V.; 20060524-20060528; Mannheim; DOC06hnod351 /20060424/
    Publication Date: 2006-04-25
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 10
    Keywords: CANCER ; CELLS ; EXPRESSION ; tumor ; TUMOR-CELLS ; carcinoma ; CELL ; evaluation ; Germany ; VIVO ; DRUG ; PATIENT ; TRANSPORT ; TRIAL ; ASSAY ; chemotherapy ; HEAD ; NECK ; squamous cell carcinoma ; GLUCOSE ; sensitivity ; GREECE ; head and neck ; METABOLITE ; PHASE-II ; AGENT ; targeting ; CELL CARCINOMA ; chemosensitivity ; D-19575 ; D-GLUCOSYLISOPHOSPHORAMIDE MUSTARD ; EUROPEAN ORGANIZATION ; EX-VIVO ; glufosfamide ; head and neck carcinoma ; HNSCC ; INFUSION ; TRANSPORTER
    Abstract: Background: Glufosfamide is a novel alkylating agent in which the active metabolite of isophosphoramide mustard is glycosidically linked to beta-D-glucose. Targeting the elevated glucose uptake of tumor cells expressing the SAAT1 glucose transporter, glufosfamide represents an attractive new drug for cancer chemotherapy. The present study investigates the ex vivo responsiveness of Head and Neck Squamous Cell Carcinoma (HNSCC) specimens to glufosfamide. Patients and Methods: Twenty-one unselected HNSCC specimens were investigated using a novel ex vivo colony formation assay to determine the epithelial drug response. The individual responsiveness to glufosfamide and to cis-platinum was determined. Results: Five out of 21 evaluable HNSCC specimens were sensitive to glufosfamide. There was a tendency for glufosfamide sensitivity in platinum-resistant specimens and vice versa. Conclusion: The effectiveness of glufosfamide observed in the present ex vivo study suggests at least an equipotentiality of glufosfamide in comparison to cis-platinum. The potential clinical usefulness of glufosfamide in HNSCC warrants further evaluation
    Type of Publication: Journal article published
    PubMed ID: 15517901
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