Biomedical subjects

H Lyng

Publications and source records attributed to H Lyng.

44 records · Page 3Linked to original sources

PubMed1992

Blood flow in six human melanoma xenograft lines with different growth characteristics.

Blood flow in six human melanoma xenograft lines grown s.c. in BALB/c-nu/nu mice was studied and analyzed in relation to tumor growth characteristics. Two different methods were used to measure blood flow, i.e., uptake of 86Rb and clearance of 133Xe. The percentage of the injected 86Rb taken up per g of tumor tissue and the 133Xe clearance rate were used as parameters for blood flow. The results achieved with these two methods were consistent. Blood flow differed significantly among individual tumors of the same line, even for tumors of similar size. All lines showed a decrease in blood flow with increasing tumor volume. This was due to an increase in necrotic fraction as well as a decrease in blood supply per viable tumor cell. Blood flow also differed significantly among the xenograft lines. All lines showed a lower blood flow than the kidney, spleen, liver, and foot. The blood flow was generally lower in the xenograft lines than in the EMT6 and Lewis lung murine tumor lines. There was no correlation between tumor blood flow and volumetric growth rate. The xenograft lines could be divided into two distinct groups of three lines each with respect to blood supply per viable tumor cell. The three lines showing a high blood supply also showed a high fraction of cells in S phase (23-31%), whereas the three lines showing a low blood supply had a low fraction of S-phase cells (11-13%). Thus, blood supply per viable tumor cell was probably decisive for the cell proliferation activity in the tumors. Moreover, necrotic fraction increased with increasing tumor volume, and the magnitude of this increase was largest for the three lines showing the lowest blood supply per viable tumor cell. These observations were possibly consequences of basic differences in vascular architecture between the two groups of xenograft lines.

Animals↗

PubMed1991

Temperature distribution in locally advanced breast carcinoma during hyperthermic treatment: relationship to perfusion, vascular density, and histology.

Temperature distributions achieved during hyperthermic treatment of 16 patients with locally advanced breast cancer were analyzed in relation to tissue perfusion, vascular density, and histology of treated volume. Temperatures were measured using multi-sensor thermistor probes inserted in the center and periphery of the treatment volume. A steady state temperature, Ts, and a perfusion related parameter, PERF, were determined for each probe location. Vascular density and tissue composition were determined by histologic analysis of biopsies taken from the temperature probe locations before treatment. Both malignant and normal tissue were found in the biopsies, reflecting a diffusive tumor growth pattern. The malignant and normal tissue compartments were analyzed separately using stereologic techniques. Ts, PERF, vascular density, and tissue composition differed significantly between patients. There was a clear relationship between Ts and PERF, showing that the local tissue perfusion was decisive for the temperatures achieved. Ts and PERF showed a clear correlation with the normal tissue vascular density, but not with the malignant tissue vascular density; that is, the treatment temperatures achieved were mainly determined by the vascularization of the normal tissue compartment. Fraction of necrosis was the only tissue compartment parameter that showed a clear relationship to Ts and PERF. Ts increased and PERF decreased with increasing necrotic fraction.

Adult↗

PubMedDate not supplied

The relevance of tumour and surrounding normal tissue vascular density in clinical hyperthermia of locally advanced breast carcinoma.

It follows from the present work that the vascularization of the normal tissue present in the treatment volume limits the temperatures achieved during heat treatment of invasive ductal breast carcinoma. The temperatures can often be increased by giving fractionated heat treatment because heat treatment may reduce the cooling capacity of the normal tissue vasculature. Significant damage to supplying vessels occurs at the heat doses necessary to cause necrosis in the tumour and surrounding normal tissue, indicating that secondary cell death is an important mechanism for cell inactivation following hyperthermic treatment of breast carcinoma.

Blood Vessels↗

PubMedDate not supplied

Treatment failure following sequential thermoradiotherapy of locally advanced breast carcinoma occurs primarily in poorly vascularized tumors.

Sequential thermoradiotherapy was given to 24 patients with locally advanced breast carcinoma. The outcome of treatment was analyzed in relation to the thermal dose as well as clinical stage, tumor volume, vascular density and necrotic fraction prior to treatment. Complete or partial response was seen in all patients. Three of the patients showed local recurrence following treatment. One of the recurrences was due to a geographic miss of the radiation therapy whereas the other two recurrences were 'true' local treatment failures. Local treatment failure could not be attributed to an advanced clinical stage, large tumor masses or poor tumor heating. The recurrent tumors had a low vascular density and significant necrotic fraction prior to treatment, suggesting that treatment failure was due to the presence of chronic hypoxia. The radiotherapeutic problem of treatment resistance caused by chronically hypoxic cells is probably not eliminated with sequential thermoradiotherapy.

Breast Neoplasms↗

PubMedDate not supplied

Positioning of temperature measurement points using multiplanar computed tomography.

A method is described for the use of computed tomography and multiplanar reconstruction to depict in single images the full course of obliquely running thermometry catheters. In 14 patients given thermoradiotherapy for locally advanced breast carcinoma, reformatted images of the full catheter course were obtained for all 98 catheters so far tested. The main clinical advantage of this time-consuming procedure was the ability to determine the localization within the catheters of individual temperature measurement points of multipoint thermistor probes. It was also possible to study the localization of the measurement points in relation to the tumour margins.

Breast Neoplasms↗

PubMedDate not supplied

Relationships between thermal dose and heat-induced tissue and vascular damage after thermoradiotherapy of locally advanced breast carcinoma.

Twenty-four patients with locally advanced breast carcinoma were given thermoradiotherapy, and heat-induced damage to tissue and vasculature was studied in relation to thermal dose. Thermometry was performed using six to eight multi-point thermistor probes. Heat-induced damage was quantified by histopathological analysis of biopsies taken from the temperature probe locations shortly after treatment. Both tumour and normal tissue were found in the biopsies. Fraction of tissue and fraction of vessels with heat-induced damage were determined for the malignant and the normal tissue compartment separately, using stereological techniques. Clear relationships were found between these parameters and the largest thermal dose achieved in one heat fraction. The data were subjected to logit analysis, and the thermal doses (eqv. min at 43 degrees C) that caused massive necrosis in 50% of the tissue were calculated to be 116 +/- 31 for the malignant tissue compartment and 205 +/- 49 for the normal tissue compartment. Similarly, the thermal doses that caused damage to 50% of the vessels were found to be 63 +/- 34 and 144 +/- 46 for the malignant and the normal tissue compartment, respectively. Thus, the tumour tissue was more sensitive to heat than was the surrounding normal tissue, irrespective of whether necrosis or vessel damage was considered. This was probably a consequence of physiological and vascular differences between the two tissue compartments. Evidence for primary and secondary cell death was found both in the malignant and the normal tissue, although primary cell death probably was of minor importance in the normal tissue. The data indicate that selective heat-inactivation of tumour tissue is possible by external microwave hyperthermia of locally advanced breast carcinoma.

Blood Vessels↗

PubMedDate not supplied

Changes in temperatures and thermal doses with fraction number during hyperthermic treatment of locally advanced breast carcinoma.

Seventeen patients with locally advanced breast cancer were given hyperthermic treatment, and changes in temperatures and thermal doses with fraction number were studied. The changes were related to the vascular density of the treated volume before treatment. Multi-point thermistor probes were used for temperature measurements. Two parameters were determined for each probe location, a steady-state temperature, Ts, and a thermal dose, t43. To quantify changes in Ts and t43, linear curves were fitted to plots of these temperature parameters versus fraction number. The slopes of the curves, kTs and kt43, were used to represent the changes in Ts and t43, respectively. Vascular density was determined by histological analysis of biopsies taken from the temperature probe locations before the first heat treatment. Generally, Ts and t43 increased with increasing fraction number. kTs and kt43 were positively correlated to the vascular density of the normal tissue in the treatment volume, i.e. the increase in Ts and t43 was largest in the best-vascularized tissue. The cooling capacity of the normal tissue was probably reduced during the later heat fractions, either because of direct damage to the blood vessels or because of an impaired thermoregulative response. No relationship was found between the temperature parameters and the vascularization of the malignant tissue in the treatment volume. The present results show that the use of a fractionated schedule for heat treatment of locally advanced breast carcinoma may increase the temperatures and thermal doses achieved during treatment. A more uniform heating of the tumours can therefore be achieved by giving multiple heat fractions in the tumour areas that are difficult to heat adequately in one session.

Body Temperature↗

PubMedDate not supplied

Thermal dose and secondary tumour cell death.

Both primary and secondary tumour cell death may occur in clinical hyperthermia. The equation usually used for calculation of thermal dose takes only the primary cell death into consideration. We propose that the thermal dose equation should be reassessed; contributions from secondary cell death should also be included. The secondary cell death is governed mainly by the temperature distribution during treatment, the arteriolar density distribution in the tumour and the heat sensitivity of the arterioles. Increased thermal dose and hence increased tumour treatment response may result if hyperthermic treatments are designed to maximize the secondary cell death. Massive secondary cell death may be achieved by inducing hot spots in tumour areas with high arteriolar density, identified in pretreatment tumour angiograms.

Animals↗