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Biomedical subjects

M B Lilly

Publications and source records attributed to M B Lilly.

27 records · Page 2Linked to original sources
PubMed1985

Direct relationship between high-energy phosphate content and blood flow in thermally treated murine tumors.

In vivo 31P-nuclear magnetic resonance (NMR) spectroscopy and 133Xe clearance were used to monitor serially ATP content and blood flow, respectively, in C3H/HeJ mouse subcutaneous RIF-1 tumors treated with hyperthermia. There was a prompt decrease in ATP [measured spectroscopically and expressed as the ratio of ATP to Pi (ATP/Pi)]. The slope and magnitude of the change in ATP closely paralleled those of tumor blood flow. Close correlation between these two variables was seen when data were analyzed both by treatment group and by individual mouse. Ligated tumors showed qualitatively and quantitatively similar changes in ATP/Pi and blood flow. RIF-1 cells heated in vitro to a similar degree showed no decrease in ATP. The loss of ATP in subcutaneous RIF-1 tumors heated in vivo was primarily due to disruption of tumor blood flow. These data emphasize the importance of vascular factors to in vivo thermal effects. In vivo 31P-NMR spectroscopy can be used to monitor indirectly vascular effects from hyperthermia.

Adenosine Triphosphate↗
PubMed1985

Hyperthermia induction with thermally self-regulated ferromagnetic implants.

We have developed a self-regulating thermoseed for interstitial hyperthermia treatment of tumors. The seeds are made of a 70.4% nickel-29.6% copper alloy, and they have a Curie point at 50 degrees C. When exposed to an oscillating magnetic field (90 kHz, 50 Oersted amplitude), these seeds show a sharp drop in the rate of heat production at temperatures above the Curie point. In a simulated treatment of a small visceral mass that had negligible blood flow, the tissue temperature stabilized at the Curie point of the alloy with good temperature homogeneity throughout the volume heated by an array of thermoseeds.

Alloys↗
PubMed1984

Local hyperthermia with interstitial techniques.

The heating of deep visceral tumors with implanted electrodes and with self-regulating ferromagnetic thermoseeds was investigated. Clinical trials on six patients heated with implanted electrodes indicate that good local tumor control can be obtained by application of hyperthermia during a normal course of radiotherapy. The heating method was found practical, and neither toxicity nor severe patient discomfort was encountered. However, temperature inhomogeneity within the tumor volume remains a problem. Theoretical studies and an animal experiment indicate that temperature homogeneity can be largely improved by heating the tumor with thermoseeds made of an alloy of 70.4% nickel and 29.6% copper. The highly temperature-dependent rate of heat production in the vicinity of the Curie point, about 50 degrees for this material, provides automatic temperature regulation.

Body Temperature↗
PubMed1984

Loss of high-energy phosphate following hyperthermia demonstrated by in vivo 31P-nuclear magnetic resonance spectroscopy.

We have used in vivo 31P-nuclear magnetic resonance spectroscopy to study the changes in high-energy phosphates following hyperthermia. Immediately after heating, there is a fall in adenosine triphosphate and apparent intracellular pH and an increase in inorganic phosphate. Following sublethal heating (40 degrees for 15 min), these changes were partial, and they resolved over the subsequent 45 hr. With tumors given severe hyperthermia (47 degrees for 15 min), there was complete disappearance of adenosine triphosphate, with no recovery by 24 hr posttreatment. Qualitatively similar effects were seen after heating of normal leg muscle. The degree of fall of the adenosine triphosphate/inorganic phosphate concentration ratio was directly proportional to the heat dose and to thermal cell kill. 31P-Nuclear magnetic resonance spectroscopy may be useful in thermal dosimetry and treatment evaluation following hyperthermia.

Animals↗
PubMed1984

Reduction of tumor burden in a murine osteosarcoma following hyperthermia combined with cyclophosphamide.

A radiation- and chemotherapy-resistant murine osteosarcoma was used to investigate the effect of local hyperthermia (42.5 +/-0.1 degrees, 30 min) alone and in combination with cyclophosphamide. The cytotoxicity of cyclophosphamide on murine osteosarcoma was established previously in our laboratory. Local hyperthermia (42.5 +/- 0.1 degree, 30 min) had little or no effect on the 16-day-old (206 X 10(6) osteosarcoma tumor cells/mouse) tumor as shown by the changes in the tumor cell marker, alkaline phosphatase. A 2.5 +/- 3.5% reduction in the number of tumor cells was seen. Large tumors treated at 21 days postimplantation (357 X 10(6) tumor cells) showed a reduction of 24 +/- 14%. The effect of combination treatment with cyclophosphamide and hyperthermia produced greater reduction in the numbers of tumor cells than did either treatment used alone.

Animals↗
PubMed1983

Hyperthermia with implanted electrodes: in vitro and in vivo correlations.

Hyperthermia as a treatment for cancer has elicited much recent interest. However, major difficulties persist both in the technology for heating deep-seated tumors, and in thermal dosimetry. We have investigated a heating technique for deep-seated neoplasms that employs an internal implanted electrode and an external electrode to apply radiofrequency current to a tumor mass. The internal electrode consists of an array of stainless steel needles or wires which define a Faraday cage within the tumor, while the external electrode consists of a variety of electrical conductors at the skin surface. Phantom measurements have closely reproduced calculated temperature distributions. The temperature profiles within the volume enclosed by the internal electrode show relatively homogenous heating. Temperature measurements in a rat tumor model have demonstrated that significant heating within such an internal electrode array is easily obtained. The heating may extend some centimeters outside the electrode. Using a dog model we have shown that with such a treatment technique the temperature profiles obtained are reproducible both spatially and temporally. A case report of a clinical application is presented. A 5 cm bronchogenic carcinoma was easily heated without significant heating of the surrounding normal lung, and without apparent toxicity. Such a technique may be applicable to a variety of operable but unresectable neoplasms. The reproducibility and relative homogeneity of heating suggest possible usefulness in combined modality trials.

Adenocarcinoma↗
PubMed1983

In vivo 31P NMR study of the metabolism of murine mammary 16/C adenocarcinoma and its response to chemotherapy, x-radiation, and hyperthermia.

(31)P NMR spectroscopy with surface coils has been used to monitor, in vivo, the phosphate metabolism of subcutaneously implanted mammary 16/C adenocarcinoma in C3H/He mice. This model tumor was studied during untreated tumor growth and after treatment with adriamycin, hyperthermia, and x-radiation. The mammary 16/C tumor exhibited a Gompertzian growth pattern. Levels of high-energy phosphate metabolites-phosphocreatine and ATP-decreased with increases in tumor mass. There was a concomitant increase in the level of P(i) and a decrease in the apparent pH of the tumor. These spectral changes appear to reflect changes in tumor vascularization that accompany tumor growth, the tumor becoming progressively more hypoxic. Partial response of this tumor to chemotherapy with adriamycin was reflected in a small but measurable increase in the phosphocreatine resonance, a decrease in P(i), and a return of the intra-tumor pH to neutral. Hyperthermia resulted in progressive conversion of the (31)P NMR spectrum to that of a dead tumor (high levels of P(i), small levels of residual sugar phosphates and pyridine dinucleotides, and acidic pH). X-irradiation (14.0 Gy) led to disappearance of the phosphocreatine peak within 15 min of treatment. Subsequently, this resonance grew back beyond its pretreatment level. As the tumor receded, its spectrum reflected the characteristics of aerobically metabolizing tissue (high levels of phosphocreatine and ATP and low levels of P(i) and sugar phosphates).

Adenocarcinoma↗
PubMedDate not supplied

Hyperthermia of pet animal tumours with self-regulating ferromagnetic thermoseeds.

Investigations with thermally self-regulating ferromagnetic implants (thermoseeds) were done on healthy rats and pet animals with spontaneous and transmissible venereal tumours (TVT). The thermoseeds were produced from a nickel-copper alloy and electroplated with a gold-silver layer. Manufacturing conditions were varied to produce thermoseeds with various operating temperatures, the critical temperature above which heating power production sharply declines. To test for toxicity, thermoseeds were implanted into the liver of rats and left in place for up to 14 months. While atomic absorption spectroscopy showed increased nickel and copper levels in tissues near the implants, no clinical evidence of ill-effects was noted. For hyperthermia treatment, thermoseeds were implanted into tumours of pet animals, and these were placed into an induction coil which produced an 89 kHz frequency, 4000 A/m amplitude field. The highest recorded tumour temperature correlated with the nominal operating point of the thermoseeds, demonstrating their ability to regulate the temperature. Of the 15 evaluable animals with spontaneous tumours treated, 12 received concomitant 60Co radiation (two of them only after tumour recurrence following an initial treatment course of hyperthermia alone). Five of those treated with both modalities experienced complete response, five responded partially and two had no change. The treatment course of hyperthermia alone resulted in one animal achieving a complete response, and in three partial responders. Animals bearing TVT had a complete local response with hyperthermia alone. Massive tissue necrosis and seed migration caused the major treatment-related toxicity. Our findings suggest that self-regulating thermoseeds offer the possibility of predictable heat delivery to defined tissue volumes, and may be useful in the treatment of human tumours which are amenable to implantation. Until migration can be controlled, clinical trials should be limited to removable implants.

Animals↗