Your email was sent successfully. Check your inbox.

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

Proceed reservation?

Export
Filter
  • ADVANCED SOLID TUMORS  (2)
  • 1
    Keywords: RECEPTOR ; SPECTRA ; ANGIOGENESIS ; CANCER ; GROWTH ; GROWTH-FACTOR ; IN-VITRO ; INHIBITOR ; proliferation ; SURVIVAL ; tumor ; ADVANCED SOLID TUMORS ; AGENTS ; ANGIOSTATIN ; BLOOD ; carcinoma ; CELL ; CELL LUNG-CANCER ; CELL-PROLIFERATION ; CLINICAL-TRIAL ; COMBINATION ; DOPPLER ; ENDOTHELIAL GROWTH-FACTOR ; evaluation ; FACTOR RECEPTOR ; Germany ; human ; IN-VIVO ; INHIBITION ; KINASE ; LUNG ; MICROSCOPY ; MICROVESSEL DENSITY ; MODEL ; MODELS ; neoplasms ; PATHWAY ; PATHWAYS ; PERFUSION ; PHASE-I ; PROSTATE ; RECOMBINANT HUMAN ENDOSTATIN ; THERAPY ; TOXICITY ; tumor growth ; TYROSINE KINASE ; VITRO ; VIVO
    Abstract: The multifaceted nature of the angiogenic process in malignant neoplasms suggests that protocols that combine antiangiogenic agents may be more effective than single-agent therapies. However it is unclear which combination of agents would be most efficacious and will have the highest degree of synergistic activity while maintaining low overall toxicity. Here we investigate the concept of combining a "direct" angiogenesis inhibitor (endostatin) with an "indirect" antiangiogenic compound [SU5416, a vascular endothelial growth factor receptor 2 (VEGFR2) receptor tyrosine kinase (RTK) inhibitor]. These angiogenic agents were more effective in combination than when used alone in vitro (endothelial cell proliferation, survival, migration/invasion, and tube formation tests) and in vivo. The combination of SU5416 and low-dose endostatin further reduced tumor growth versus monotherapy in human prostate (M), lung (A459), and glioma (U87) xenograft models, and reduced functional microvessel density, tumor microcirculation, and blood perfusion as detected by intravital microscopy and contrast-enhanced Doppler ultrasound. One plausible explanation for the efficacious combination could be that, whereas SU5416 specifically inhibits vascular endothelial growth factor signaling, low-dose endostatin is able to inhibit a broader spectrum of diverse angiogenic pathways directly in the endothelium. The direct antiangiogenic agent might be able to suppress alternative angiogenic pathways up-regulated by the tumor in response to the indirect, specific pathway inhibition. For future clinical evaluation of the concept, a variety of agents with similar mechanistic properties could be tested
    Type of Publication: Journal article published
    PubMed ID: 14695206
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: ANGIOGENESIS ; CANCER ; ENDOTHELIAL-CELLS ; GROWTH ; ADVANCED SOLID TUMORS ; PHASE-I ; RECOMBINANT HUMAN ENDOSTATIN ; SYSTEM ; SURGERY ; resistance ; NUMBER ; COLORECTAL-CANCER ; chemotherapy ; systems biology ; HEMATOPOIETIC STEM-CELLS ; I CLINICAL-TRIAL ; cancer therapy ; ENDOSTATIN ; ANGIOGENESIS INHIBITOR ENDOSTATIN ; COLLAGEN XVIII ; ENDOGENOUS INHIBITOR ; ENDOTHELIAL PROGENITOR CELLS ; RESPONSIVENESS
    Abstract: The hypothesis that tumor growth and metastasis is angiogenesis-dependent was proposed by Judah Folkman in 1971. Its major implication is that blocking angiogenesis could be a strategy for arresting tumor growth. This hypothesis is now supported by extensive experimental evidence, and hence the angiogenic switch and microvascular endothelial cells recruited by the tumor have emerged as important targets in cancer therapy. A large number of proangiogenic and antiangiogenic factors have been discovered. At least three angiogenesis inhibitors have received FDA approval in the US, with Avastin (anti-VEGF-antibody) also approved in 26 other countries. The recognition that antiangiogenic therapy is becoming the fourth therapeutic modality in addition to surgery, chemotherapy and radiotherapy underlines the urgent need to understand the systems biology of the antiangiogenic response. A particularly important question for cancer therapy is whether antiangiogenic therapy will also face the same drug resistance as one sees with other treatment modalities. Recently, the cellular signaling induced by the endogenous angiogenesis inhibitor - endostatin - was dissected revealing that the antiangiogenic response is characterized by a large number of individual genetic signals, which are highly coordinated and interdependent. The objective of this review is to elucidate the multifaceted nature of tumor angiogenesis, and to discuss the subtle but important distinctions that exist between variations in tumor responsiveness that evolve with antiangiogenic therapy and the classic resistance that frequently develops with conventional therapy. Furthermore, this review discusses the implications of current findings for cancer treatment and potential ways of overcoming or predicting tumor resistance to these agents. (c) 2005 Elsevier Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 15939343
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...