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  • 1
    ISSN: 1619-7089
    Keywords: Key words: Deoxyglucose ; Methionine ; Fluorine-18 fluoromisonidazole ; Autoradiography ; Hypoxia ; Positron emission tomography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 14 C-2-deoxyglucose (2DG) and 14C-methionine (Met). The study was performed using control rats with the AH109A tumour and rats with the same tumour under local hypoxia. Tumour uptake of FMISO was constant between 30 min and 2 h after injection, and the tumour to muscle ratio was 2 from 2 to 4 h. A tumour study with FMISO was scheduled at 2 h. Double-tracer autoradiography of the tumour demonstrated that in the areas of high FMISO uptake, there was low uptake of Met, while areas of low FMISO uptake showed high Met uptake. FMISO showed high grain density in the rim of the tumour surrounding the necrotic area. 2DG showed a more uniform distribution over the entire section of viable cells. The mean uptake of FMISO by hypoxic, radioresistant tumours was significantly higher than that by the control tumours (P〈0.05), while both 2DG and Met uptake by the control tumours was higher than uptake by hypoxic tumours. When individual tumours were examined, the uptake of FMISO was inversely correlated with that of Met (r = –0.507, P〈0.02), while 2DG showed almost uniform uptake with no significant correlation to FMISO. In conclusion, hypoxic and radioresistant tumours could be identified by increased FMISO uptake in our model, consistent with findings reported by others. We found a large overlap in the distribution of FMISO and 2DG within the tumour, but only a small overlap in the distribution of FMISO and Met. A combination of FMISO and other tracers in positron emission tomography or single-photon emission tomography studies might be more helpful than single-tracer studies in predicting the response of tumour tissues to radiotherapy.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7233
    Keywords: drug response ; size dependency ; cellular heterogeneity ; tissue inhomogeneity ; drug delivery ; tumor blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The response of cancer to various anticancer drugs is tumor-size dependent in many aspects. In general, problems stem partly from the fact that the entire tumor cell populations do not respond equally to a certain treatment. As a result of recent progress in cancer biology, it has become evident that cellular heterogeneity of the tumor underlies the difficulties of treating primary and metastatic tumors with chemotherapy. Moreover, as tumors grow, marked diversity develops on the tissue level as well. An uneven distribution with an increase of areas of lower growth fraction and of poorer drug delivery is more distinct in larger tumors. Heterogeneous distribution and low levels of tumor blood flow are considered to be causally related to the heterogeneous nature of tumor tissue. Considering the lack of evidence of a lymphatic system within the tumor, increased interstitial fluid pressure may be a natural result that further impedes blood flow in the tumor. The fact that the temporary and selective increase in tumor tissue blood flow by angiotensin-induced hypertension produces a remarkable chemotherapeutic effect should vividly indicate that delivery of the drug to the tumor is really the ‘bottleneck’ of cancer chemotherapy. Tumor-size-related change in the transvascular and extravascular transport of molecules and its relevance to chemotherapy are also discussed in this article.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Cancer and metastasis reviews 3 (1984), S. 115-126 
    ISSN: 1573-7233
    Keywords: tumor blood flow ; angiotensin II ; microhemodynamics ; cancer chemotherapy ; oxygen tension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This review describes some aspects of tumor vessels and the influence of vasoactive agents on tumor blood flow, particularly the characteristic microcirculation of tumors with regard to its selective increase in blood flow. Elevation of blood pressure by infusion of angiotensin II produced a severalfold increase in tumor blood flow. The increase was selective and specific to the tumor vessels as long as the mean arterial blood pressure was kept under 150 mm Hg. Pressure elevation by angiotensin II also selectively increased tumor oxygen tension and influx of lymph flow from the primary transplanted lesion to the lymph node metastatic lesion. Newly devised techniques for analyzing microhemodynamics of tumor vessels showed that the velocity of tumor blood flow, the vascular area in tumor tissue, and the hydrostatic pressure difference between the tumor vessel and extravascular tissue were markedly enhanced. Thus, the extravasation of material into tumor tissues can be increased by the enhancement of blood flow. This demonstration allowed the development of a new approach to cancer chemotherapy, in which the delivery to tumor tissue of systemically administered anticancer drugs can be selectively enhanced.
    Type of Medium: Electronic Resource
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