0000000000400199
AUTHOR
M. Hoeckel
Current Status of Knowledge and Critical Issues in Tumor Oxygenation
In 1972 we started the systematic investigation of oxygenation status in (a) experimental tumor systems in rats and mice [e.g., 1–6], (b) in human tumors xenotransplanted into immune-deficient rnu/rnu-rats [e.g., 7–9], (c) in tumors derived from spontaneously tumorigenic or ras-transformed cell lines [10], and (d) in human tumors in situ [e.g., 11–15] under various pathophysiological conditions using polarographic O2 needle electrodes. In the earlier studies a cryospectrophotometric ex vivomicrotechnique was also used that allowed the measurement of HbO2 saturation in individual red blood cells in tumor microvessels [e.g., 16, 17]. Besides polarographic and cryospectrophotometric microtechn…
The Role of Oxygen Tension Distribution on the Radiation Response of Human Breast Carcinoma
The response of tumors to radiation is heterogeneous even in animal tumor systems where tumors all originate from the same cell culture, are implanted in genetically similar age-matched animals in a constant anatomic locationl. Hence great heterogeneity of response exists even in situations where intrinsic genetic or epigenetic factors are minimally variable. Several metabolic factors are known to influence the probability of tumor control after radiation. These metabolic factors are also known to vary widely between tumors in humans2,3 and even in animal tumor models. Heterogeneous variables include tumor oxygen tension distribution, glutathione content, glucose delivery and utilization ra…
Predictive Power of the Tumor Oxygenation Status
In most solid tumors the tissue pO2 status is poorer than in normal tissue at the site of tumor growth (for reviews see Vaupel et al., 1996, 1998; Vaupel and Hoeckel, 1998). Peculiarities of tumor tissue oxygenation can mainly be attributed to characteristic structural and functional abnormalities of the tumor microcirculation (perfusion-limited O2 delivery), to a deterioration of the diffusion-geometry (diffusion-limited O2 delivery), and—in some cases—to a reduced O2 carrying capacity of the blood due to tumor-associated anemia.
The anatomic basis of the transversus and rectus abdominis musculoperitoneal (TRAMP) composite flap
The aim of this study was to provide an anatomic basis for the transversus and rectus abdominis musculoperitoneal (TRAMP) flap, recently successfully introduced for vulvovaginal reconstruction. In 25 cadavers the width and length of the portions of rectus and transversus abdominis muscles suitable for the TRAMP flap as well as the length and diameter of the inferior epigastric artery were assessed. The mean length of the rectus abdominis muscle was 32.42±0.48 cm and its width 6.15±0.12 cm. The suitable part of the transversus abdominis muscle measured 19.08±0.3 cm mean length with a mean width of 18.62±0.19 cm. No significant left-right differences were observed. The resulting area of the r…
Pathophysiological approaches to identifying tumor hypoxia in patients
The present report summarizes observations of the authors on tumor oxygenation and on techniques for characterizing tumor hypoxia in patients. Cryospectrophotometric measurements of HbO2 saturations in tumor microvessels allow for estimates of the proportion of well oxygenated tissue regions. Labeling of tissue areas at oxygen (O2) tensions (pO2) less than 10 mm Hg with misonidazole may be used for a general characterization of the oxygenation status in patient tumors rather than for the determination of the radiobiologically hypoxic cell fraction. Quantitative bioluminescence and single photon imaging make it possible to determine ATP concentrations in absolute terms with a spatial resolut…
Oxygenation of Mammary Tumors: From Isotransplanted Rodent Tumors to Primary Malignancies in Patients*
The role of oxygen in tumor cell proliferation, radiosensitivity, cytotoxicity of anticancer drugs and hyperthermia treatment has been the subject of a series of investigations (for reviews see Hall, 1988; Teicher et al., 1990, Vaupel et al., 1989a; Vaupel, 1990a,b). Despite the apparent importance of tumor oxygenation, data on pO2 values in solid tumors are mostly derived from experiments on rodents which might not necessarily reflect the variability of the clinical situation. Due to feasible techniques available now, considerable advances have been made in the past few years in the assessment of tumor hypoxia in patients (for reviews see Vaupel et al., 1989a; Vaupel, 1990a). The latter in…
Blood Flow and Tissue Oxygenation of Human Tumors: An Update
It is generally accepted that tumor microcirculation, blood flow, oxygen and nutrient supply, tissue pH distribution, and the bioenergetic status (factors which are usually closely linked and which define the so-called cellular microenvironment) can markedly influence the therapeutic response of malignant tumors. Tumor blood flow is the major determinant for intra-tumor pharmacokinetics and (through modulation of the cellular microenvironment) of pharmacody-namics. The oxygen supply greatly determines the radiosensitivity of the tumors to be treated. The oxygen enhancement ratio, i.e., the ratio of doses with and without oxygen to produce the same biological effect is 2.7 to 3.0. O2 partial…
Tumor tissue oxygenation as evaluated by computerized-po2-histography
A computerized pO2 measurement system with a novel electrode motion pattern (Sigma-pO2-histography) was evaluated in vitro and in vivo. The system was found to be reliable in 0.9% saline and 10% hydroxyethylene starch solution and in fresh donor blood. Marked deviations were found in lipid and hemoglobin solutions and in fluorocarbon emulsions. Histograms obtained in rat liver, mouse muscle, and subcutis were similar to previously reported distributions. Direct comparison between Sigma-Eppendorf and self-constructed Whalen-type electrodes in hypoxic tumors gave similar results. A large series of measurements indicated that hypoxic and anoxic tissue areas were frequently found both in isogra…