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  • 1
    Electronic Resource
    Electronic Resource
    Markers of tumor angiogenesis: clinical applications in prognosis and anti-angiogenic therapy (1997)
    Springer
    Investigational new drugs 15 (1997), S. 15-28 
    Details
    ISSN: 1573-0646
    Keywords: angiogenesis ; prognosis ; histology ; methods
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Numerous studies in many tumor types have demonstrated that quantitation by microvessel as a measure of angiogenesis is a powerful prognostic tool. However, the ability to exploit tumor angiogenesis as a prognostic marker is limited by the methods currently used for capillary identification and quantitation. This report critically evaluates all aspects of the techniques and their associated problems used for assessing tumor angiogenesis in tissue sections including the area of tumor assessed, the vascular parameter measured, the method of quantitation, the stratification of patients and the practical utility of computer image analysis systems. The potential of angiogenic factors assays, proteolytic enzymes, and cell adhesion molecules as surrogate endpoints for quantifying tumor angiogenesis are discussed and other methods for quantifying tumor angiogenesis are described. The potential clinical applications of these angiogenic markers in prognosis, stratification for adjuvant treatments (both cytotoxic and anti-angiogenic/vascular targeting) and other aspects of patient management is also discussed, particularly design of phase I and II trials.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1005714527315
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    The epidermal growth factor receptor as a prognostic marker: Results of 370 patients and review of 3009 patients (1994)
    Springer
    Breast cancer research and treatment 29 (1994), S. 41-49 
    Details
    ISSN: 1573-7217
    Keywords: breast neoplasms ; epidermal growth factor receptor ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Epidermal growth factor receptor (EGFR) and estrogen receptor (ER) were assayed by ligand binding in tumors from 370 patients with primary breast carcinoma with a median follow up of 18 months. Forty seven percent (175/370) and 57% (210/370) of tumors had 〉20 fmol/mg and 〉10 fmol/mg of EGFR and ER respectively. There was a highly significant inverse relationship between EGFR and ER (p=0.0032). There was also a significant association between EGFR and patient age (p=0.0006) but no correlation between EGFR and lymph node status, tumor grade, or tumor size (p=0.104, p=0.198, and p=0.085 respectively). In a univariate analysis of all patients, EGFR expression was not associated with a significant reduction in overall survival (OS). However, there was a significant decrease in relapse-free survival (RFS) and OS in node negative EGFR positive patients (p=0.03 and p=0.05 respectively). In a multivariate analysis (Cox proportional hazard model) of all patients, lymph node status was an independent prognostic indicator for OS and RFS (p〈0.00005 and p=0.00005 respectively), ER status for RFS (p=0.0006), and EGFR (in the node negative model) for RFS (p=0.03). When all patients were stratified for EGFR and ER, there was a significant difference in RFS and OS such that EGFR positive and ER negative had the worst prognosis (p=0.0034 and p=0.005 respectively). A similar relationship was observed for OS in node negative patients (p=0.004) and for RFS in node positive patients (p=0.009). In a review of 3009 patients with follow-up, 11/16 series showed high EGFR was associated with shorter RFS or OS in univariate analysis, and 4 showed this in multivariate analysis. However, most series had inadequate follow-up time and most did not include multivariate analysis. This highlights the need for uniform criteria of reporting trials of prognostic factors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666180
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  • 3
    Electronic Resource
    Electronic Resource
    What is the biological, prognostic, and therapeutic role of the EGF receptor in human breast cancer? (1994)
    Springer
    Breast cancer research and treatment 29 (1994), S. 1-2 
    Details
    ISSN: 1573-7217
    Keywords: EGF receptor ; EGFR ligands ; epidermal growth factor (EGF) ; pathogenesis ; prognosis ; therapeutic targets
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The epidermal growth factor receptor (EGFR) is expressed in benign and malignant breast epithelium. The EGFR, when mutated or over-expressed in the presence of its ligand, is transforming in other tissues or cell types. It is therefore of major interest in the pathogenesis of human breast cancer to understand the role of EGFR and its ligands. Additionally, if differential expression is of prognostic value, or if expression provides a therapeutic target, then EGFR may be useful in clinical management and treatment of breast cancer. This issue of Breast Cancer Research and Treatment reviews the basic biology of the EGFR, related members of the EGFR family, the increasing family of ligands for EGFR, and the clinical role in breast cancer, prognosis, and therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666176
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Tumor angiogenesis in node-negative breast carcinomas — relationship with epidermal growth factor receptor, estrogen receptor, and survival (1994)
    Springer
    Breast cancer research and treatment 29 (1994), S. 109-116 
    Details
    ISSN: 1573-7217
    Keywords: angiogenesis ; breast neoplasms ; epidermal growth factor receptor ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Angiogenesis is essential for tumor growth and metastases. Studies in breast carcinomas suggest that microvessel quantitation as a measure of angiogenesis might be one of the most powerful prognostic tools available. Node negative breast cancer is a particular group for which better prognostic markers would be helpful. We therefore measured microvessel density in a series of well characterised node negative breast carcinomas to evaluate angiogenesis as a prognostic marker and assess its relationship to epidermal growth factor receptor (EGFR) and estrogen receptor (ER), which have previously been reported to be of value. 109 patients with a mean age of 55 years and a median follow-up of 25 months were examined. Vessels were immunohistochemically highlighted using an antibody to platelet endothelial cell adhesion molecule CD31, and microvessel density was quantified using a Chalkley point eyepiece graticule. No significant correlation was observed with patient age, tumor size, grade, ER, or EGFR expression. In a univariate analysis of survival, whereas ER expression was not a significant indicator of either relapse-free (RFS) or overall survival (OS), vascular count (VC) predicted both early RFS and OS (p=0.01 and p=0.028 respectively). Furthermore, in patients with ER positive tumors, a subgroup usually considered to have a good prognosis, there was a significant reduction in RFS and OS if tumors had high VCs (p=0.05 and p=0.002 respectively). A further statistically significant reduction in RFS (p=0.05) was observed for EGFR positive highly vascular tumors. In a Cox proportional hazard model, VC remained a significant prognostic indicator for both RFS and OS (p=0.04 and p=0.01) and conferred a 6.6 and 3.5 times respective increased risk of mortality and relapse. These findings suggest that quantitation of angiogenesis is an independent predictor of survival in node negative breast carcinomas, and due to these high hazard ratios might be more useful than other recently described prognostic markers in selecting patients who would benefit from adjuvant therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666186
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    Paper (German National Licenses)
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  • 5
    Electronic Resource
    Electronic Resource
    Breast cancer angiogenesis — new approaches to therapy via antiangiogenesis, hypoxic activated drugs, and vascular targeting (1996)
    Springer
    Breast cancer research and treatment 38 (1996), S. 97-108 
    Details
    ISSN: 1573-7217
    Keywords: angiogenesis ; angiogenesis inhibitors ; gene therapy ; hypoxic activated pro-drugs ; prognosis ; vascular targeting
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Several groups have shown that quantitation of tumor angiogenesis by counting blood vessels in primary breast cancer gives an independent assessment of prognosis. Poor prognosis is associated with high blood vessel counts. We have shown that the rate of cell division in endothelial cells is much higher in breast tumours than in normal breast. Breast cancer cell lines and primary human breast tumours express a wide range of vascular growth factors, including VEGF, placenta growth factor, pleiotrophin, TGFβ1, acidic and basic FGF, and platelet-derived endothelial cell growth factor. Inhibiting angiogenesis by blocking vascular growth factors would be difficult with highly specific agents, but drugs with a broader spectrum of antagonism may be effective. We have developed several suramin analogues which are less toxic than suraminin vivo but more potent in inhibiting angiogenesis, and these have been developed for Phase I. A combination of anti-angiogenesis agents with drugs activated by hypoxia may also be useful, because anti-angiogenesis alone may not kill cells, whereas activation of hypoxic drugs could synergize. New endpoints may be necessary because inhibition of new blood vessel formation may not cause tumour regression. Thus, the endpoint of stable disease and biochemical assessment of inhibition of angiogenesis may be much more important in therapeutic studies and for drug development in the future. The prognostic importance of angiogenesis suggests that this should be a major new therapeutic target.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01803788
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  • 6
    Electronic Resource
    Electronic Resource
    Bladder cancer angiogenesis, its role in recurrence, stage progression and as a therapeutic target (1996)
    Springer
    Cancer and metastasis reviews 15 (1996), S. 221-230 
    Details
    ISSN: 1573-7233
    Keywords: angiogenesis ; bladder cancer ; antiangiogenic therapy ; VEGF ; prognosis ; stage progression ; thymidine phosphorylase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this article we review the role of angiogenesis in bladder tumour development and its putative role in determining tumour progression and recurrence. The potential value of antiangiogenic therapy in the disease is also discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00437475
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