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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1573-7039
    Keywords: Tyrosine kinase receptors ; monoclonal antibodies ; breast cancer ; tyrosine kinase inhibitors ; epidermal growth factor receptor ; HER2/neu ; erbB2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Breast carcinomas express high levels of type I tyrosine kinase receptors and their ligands. For these reason therapies directed at these receptors have the potential to be useful anti-cancer agents. A series of monoclonal antibodies (MAbs)3 directed against the EGF receptor and the closely related erbB2/HER2/neu receptor are currently under evaluation. These MAbs have shown promising preclinical activity and “chimeric” and “humanized” MAbs have been produced in order to obviate the problem of host immune reactions. These antibodies are currently being tested in clinical trials either alone or in combination with chemotherapeutic agents. Clinical activity with anti-HER2/neu MAbs has been documented in patients with advanced breast cancer. In addition, compounds that inhibit receptor tyrosine kinases have shown significant preclinical activity and are potential candidates for clinical testing.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Annals of oncology 11 (2000), S. 187-190 
    ISSN: 1569-8041
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 29 (1994), S. 127-138 
    ISSN: 1573-7217
    Keywords: EGF receptor ; monoclonal antibodies ; clinical trials ; humanized antibodies ; chemotherapy ; imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The epidermal growth factor (EGF) receptor and its ligands have an important regulatory role in breast carcinoma. We have produced a series of monoclonal antibodies (MAbs) directed against the external portion of the EGF receptor. These MAbs prevent the binding of the ligands to the receptor, block ligand-induced activation of the receptor, and can inhibit the growth of breast cancer cells both in tissue culture and in human tumor xenografts in nude mice. We have also shown that anti-EGF receptor antibodies greatly enhance the antitumor effects of chemotherapeutic agents active in breast cancer. Phase I clinical trials with single doses of MAb conducted in patients with tumors over-expressing EGF receptors demonstrated favorable pharmacokinetics, good tumor imaging, and a lack of toxicity. A human:murine chimeric antibody has been produced with comparable affinity and antitumor activity that will enable us to administer repeated doses of MAb either alone or in combination with chemotherapy. Our pre-clinical data support the concept that the EGF receptor may be an optimal target for treatment with receptor blocking antibodies, either alone or in combination with chemotherapy.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1573-7039
    Keywords: BREAST CANCER ; EGF RECEPTOR ; TRASTUZUMAB ; TYROSINE KINASE INHIBITORS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Breast carcinomas express high levels of ErbBreceptors and their ligands, and their overexpressionhas been associated with a more aggressive clinicalbehavior. For these reasons therapies directed at these receptors have the potential to be usefulanti-cancer treatments. A series of monoclonalantibodies (MAbs)3 directed against the EGF(ErbB1) receptor and the closely related HER2/Neu(ErbB2) receptor are currently under evaluation. These MAbs haveshown promising preclinical activity and“chimeric” and “humanized” MAbshave been produced in order to obviate the problem ofhost immune reactions. These antibodies are currently being tested inclinical trials either alone or in combination withchemotherapeutic agents. Clinical activity with one ofthese antibodies, trastuzumab, a humanized anti-ErbB2 MAb, has been documented in patients withbreast cancer in a series of clinical trials and hasrecently been approved for the therapy of patients withmetastatic ErbB2 overexpressing breast cancer. Inaddition to antibodies, compounds that inhibit receptortyrosine kinases have shown significant preclinicalactivity and are currently being evaluated in theclinic.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Investigational new drugs 11 (1993), S. 85-86 
    ISSN: 1573-0646
    Keywords: gallium nitrate ; small cell lung cancer ; phase II trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Gallium nitrate is a group IIIa metal that was found to be active in animal species [1]. Gallium nitrate exerts its antitumor effects via a transferrin binding mechanism [2]. This agent is of interest in small cell lung cancer since 26 of 27 small cell carcinoma cell lines tested had increased levels of transferrin receptors [3]. In a phase I study using a continuous infusion, the dose limiting toxicity was nausea when gallium nitrate was given at doses of 400 mg/m2/day. Other effects included elevations of serum creatinine, hypocalcemia, hypomagnesemia, decreased hearing and paresthesias [4]. Activity has been seen in pretreated patients with malignant lymphoma, bladder carcinoma and small numbers of patients with small cell lung carcinoma [4, 5]. To determine the activity of continuous infusion gallium nitrate, this phase II trial was undertaken in patients with small cell lung cancer previously treated with chemotherapy.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 28 (1991), S. 51-54 
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A total of 21 patients with advanced soft tissue sarcoma enrolled in a phase II trial of 3.5 g/m2 N-phosphonacetyl-l-aspartate (PALA) given intravenously every 3 weeks plus 50 mg/m2 dipyridamole (Persantine) given orally every 6 h. Dipyridamole administration was initiated 1 week before the first dose of PALA. Peak and trough plasma concentrations of dipyridamole were measured before and after the first dose of PALA in 14 patients. In all, 19 patients were evaluable for therapeutic response. One subject experienced partial regression of a pulmonary metastasis; no other major response was observed. Diarrhea was the most prominent toxicity; in one patient it was life-threatening and was associated with a severe rash. On the day preceding PALA administration, the median peak plasma concentration of dipyridamole was 2,208 ng/ml and the median trough value was 904 ng/ml. Similar values were obtained on the day of PALA administration. Although the levels achieved were similar to those required to modulate the activity of PALA in preclinical systems, the therapeutic results obtained in the present study were not superior to those reported for PALA alone in previously treated patients with soft-tissue sarcoma.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature medicine 10 (2004), S. 786-787 
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] A series of clinical studies initiated in the late 1990s brought hope to patients with chronic myeloid leukemia, a low-grade malignancy that eventually transforms to a more aggressive, invariably fatal stage. The drug imatinib mesylate (STI-571, Gleevec), a tyrosine kinase inhibitor, was found to ...
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  • 8
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature medicine 8 (2002), S. 1145-1152 
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] We have shown a novel mechanism of Akt-mediated regulation of the CDK inhibitor p27kip1. Blockade of HER2/neu in tumor cells inhibits Akt kinase activity and upregulates nuclear levels of the CDK inhibitor p27Kip1. Recombinant Akt and Akt precipitated from tumor cells phosphorylated wild-type p27 ...
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  • 9
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 446 (2007), S. 137-138 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] ...How do patients who sign up for clinical trials know that the right questions are being asked and that the data support the reported answers to these questions? For many patient groups, transparency in study design, data collection and analysis, and full publication of results are issues of ...
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