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S D Prionas

Publications and source records attributed to S D Prionas.

At least 19 recordsLinked to original sources
PubMed1992

Characterization and applications of the disc angiogenesis system.

A model to study microvascular proliferation, the Disc Angiogenesis System (DAS), consists of a synthetic foam disc implanted subcutaneously in experimental animals. After a period of growth, usually 7 to 21 days, the disc is removed. Planar sections are used to measure and characterize the growth. Microvessels grow centripetally into the disc, together with fibroblasts. Concentric growth zones have been defined by light and electron microscopy. Moderate growth occurs spontaneously and is accelerated by angiogenic stimulants placed in the center of the disc. Morphometric analyses have shown that vessel growth is directly proportional to total fibrovascular growth, so the former can be quantified by procedures measuring the latter. These include manual projection of sections and computer-assisted digital image analysis, which is recommended for routine use. The proliferation of endothelial and other cells is determined by incorporation of tritiated thymidine, using scintillation counting and autoradiography. Using the DAS, well-established angiogenic agents such as basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and prostaglandin E1 were found to increase proliferation of endothelial cells (EC) and microvessels. Heparin augmented the effect of bFGF. When used by itself heparin increased angiogenesis but not EC proliferation, in keeping with in vitro observations indicating that it stimulates migration but not proliferation of EC. Locally applied hyperthermia and ionizing radiation decreased angiogenesis, even when applied after the angiogenic stimulus. Systemic prostaglandin synthetase inhibitors antagonized the angiogenic effects of bFGF and EGF, in accordance with a postulated role of prostaglandins in the transduction of proliferative signals in microvascular EC. The DAS is easy to assemble and implant in small animals, including mice, which tolerate it well. Hence multiple discs can be used for each time or dose point, which allows reproducible measurements of vascular growth and increases statistical accuracy. Another advantage of the system is the capability of discriminating between proliferation and migration of EC and fibroblasts. The DAS can be used to test putative agonists or antagonists of angiogenesis. More generally, the DAS provides a model of wound healing, either uncomplicated or complicated by inflammation, and of angiogenic responses to solid tumors.

Animals↗
PubMed1992

Parameters predictive for complications of treatment with combined hyperthermia and radiation therapy.

Pretreatment and treatment related factors were reviewed for 996 hyperthermia sessions involving 268 separate treatment fields in 131 patients managed with hyperthermia for biopsy confirmed local-regionally advanced or recurrent malignancies to ascertain parameters associated with the development of complications. A subset of 249 fields were identified in which multipoint or mapped temperature data were available for at least one treatment session per field. A total of 198 fields involved superficially located tumors (less than or equal to 3 cm from the surface), whereas 51 fields involved more deeply located tumors. Most of these patients had received extensive prior therapy: 77% had surgery, 75% chemotherapy, 65% radiation therapy and 28% hormonal therapy. They were treated with hyperthermia in conjunction with radiation therapy (244 fields) or hyperthermia alone (5 fields). The hyperthermia treatment objectives were to elevate intratumoral temperatures to a minimum of 43.0 degrees C for 45 minutes while maintaining maximum normal tissue temperatures to less than or equal to 43 degrees C and maximum intratumoral temperatures to less than or equal to 50 degrees C. The hyperthermia was given within 30 to 60 minutes following radiation therapy without the administration of additional analgesics. Hyperthermia treatment regimens using radiative electromagnetic, ultrasound, or radiofrequency interstitial techniques were individualized, with 3 to 4 days between hyperthermia treatments and an average of 3.6 treatments (range 1-14; standard deviation 2.2) utilized per field. A total of 38 complications in 33 treatment fields were noted; an incidence of 27/198 (13.6%) for fields with superficially located tumors, and 6/51 (11.8%) in fields with more deeply located tumors. Univariate analyses demonstrated statistically significant correlations between the maximum tumor temperature (p = 0.0005), average of the maximum tumor temperatures (p = 0.0006), the average of the % tumor temperatures greater than 43.5 degrees C (p = 0.0071), and the average number of hyperthermia treatments (p = 0.033), with the development of complications. The average of the maximum measured tumor temperature for fields without complications was 44.6 degrees C compared with 45.9 degrees C for fields with complications. The complication rate increased from 7.5% (9/120) in fields that received one or two hyperthermia treatments to 18.6% (24/129) in fields that received greater than two hyperthermia treatments. Multivariate logistic regression analyses revealed the best bivariate model predictive of the development of complications included average of the maximum tumor temperature and the number of treatments per field (p = 0.00012 for the bivariate model).(ABSTRACT TRUNCATED AT 400 WORDS)

Combined Modality Therapy↗
PubMed1992

Body conformable 915 MHz microstrip array applicators for large surface area hyperthermia.

The optimal treatment with hyperthermia of superficially located tumors which involve large surface areas requires applicators which can physically conform to body contours, and locally alter their power deposition patterns to adjust for nonuniform temperature caused by tissue inhomogeneities and blood flow variations. A series of 915 MHz microstrip array applicators satisfying these criteria have been developed and clinically tested. Clinical and engineering design tradeoffs for practical devices are discussed. Measurements taken in tissue equivalent phantoms and a summary of our clinical experiences with these microstrip arrays are presented.

Electric Conductivity↗
PubMed1992

Dual role of tumor necrosis factor-alpha in angiogenesis.

The role of tumor necrosis factor-alpha (TNF; cachectin) in angiogenesis has been controversial. In vitro TNF inhibits proliferation of endothelial cells (EC) whereas in the cornea it appears to stimulate vessel growth. The authors tested TNF in their recently developed disc angiogenesis system (DAS), designed to measure the proliferation of microvessels. The DAS, implanted subcutaneously in mice, was either fitted with a central pellet containing mouse recombinant TNF (mrTNF), or exposed to mrTNF delivered subcutaneously by an osmotic minipump. Low doses of mrTNF (0.01-1 ng) induced angiogenesis, which was maximum at 0.1 ng, whereas high doses (1, and 5 micrograms) inhibited it. Subcutaneous mrTNF delivered at the (high) rate of 15-60 ng/hr for 14 days inhibited angiogenesis. These results indicate bimodal, dose-dependent opposing effects and explain some of the in vitro versus in vivo paradoxical results. TNF (native or exogenous) may have opposing effects on microvessels of neoplasms and inflammatory reactions, depending on its local tissue concentrations.

Animals↗
PubMed1991

RTOG quality assurance guidelines for clinical trials using hyperthermia administered by ultrasound.

Clinical quality assurance guidelines are established for RTOG hyperthermia protocols in which unfocused planar ultrasound may be used to administer hyperthermia. Measurement of temperature at a few fixed points is no longer considered to be adequate. Thermal mapping is required to obtain profiles of the temperature across the tumor dimensions, including margins of normal tissue. The thermometry strategies established for microwaves are to be adhered to with oblique insertion of the probes recommended. Two types of errors arise which are generally not present with microwaves. A measurement error, commonly referred to as a temperature artifact, arises because of absorption and/or viscous heating of the probe. Another error arises when thermocouples are used due to the conduction of heat along the wire leads, especially the copper wire. Several thermometry systems are evaluated with regard to the expected artifact and conduction errors. Acceptable systems include: a) indexing a polyurethane sheathed single sensor thermocouple in a polyurethane catheter, b) indexing a fiberoptic probe in a steel needle, c) indexing a single sensor thermocouple in a steel needle, and d) use of manganin-constantan multisensor thermocouples. Unacceptable systems include: a) fixed or static probes that do not provide profiles of the temperature across the tumor dimensions, b) copper-constantan multisensor thermocouples, and c) teflon sheathed thermocouples inserted into a teflon catheter.

Clinical Protocols↗
PubMed1990

Novel instrumentation for multifield time-lapse cinemicrography.

The most significant feature of the system that is described is its ability to image essentially simultaneously the growth of up to 99 single cells into macroscopic colonies, each in its own microscope field. Operationally, fields are first defined and programmed by a trained observer. All subsequent steps are automatic and under computer control. Salient features of the hardware are stepper motor-controlled movement of the stage and fine adjustment of an inverted microscope, a high-quality 16-mm cine camera with light meter and controls, and a miniature incubator in which cells may be grown under defined conditions directly on the microscope stage. This system, termed MUTLAS, necessitates reordering of the primary images by rephotographing them on fresh film. Software developed for the analysis of cell and colony growth requires frame-by-frame examination of the secondary film and the use of a mouse-driven cursor to trace microscopically visible (4X objective magnification) events.

Animals↗
PubMed1990

Interstitial 192Ir flexible catheter radiofrequency hyperthermia treatments of head and neck and recurrent pelvic carcinomas.

Since September 1983, five patients with head and neck cancers and five patients with pelvic or perineal recurrences of colorectal neoplasms received 192Ir interstitial implants through flexible afterloading catheters that were modified to allow RF hyperthermia treatments of the tumor within 1 hr pre- and post-brachytherapy. Local control in the implant volume was obtained in three of the patients with head and neck cancers (base tongue--2/4; floor of mouth--1/1) with follow-up of 9 to 42 months. Two patients had local recurrences after disease-free periods of 8 and 24 months. Two of the five patients treated for pelvic recurrences had complete responses lasting less than 3 months; prolonged stabilization (12 months) of a presacral mass in a third patient also occurred, but the neoplasm eventually regrew. Average temperatures of 39.2 degrees C to 43.7 degrees C were obtained in the implant volumes of these patients during the 45 minute heating periods which took place prior to loading, and just after removal, of the 192Ir seeds in each patient. No instances of intra or post-operative hemorrhage or necrosis of bone or soft tissues occurred in these patients. However, one individual required a permanent tracheostomy for persistent epiglottic edema after implantation as part of a base-tongue brachytherapy procedure. Interstitial RF hyperthermia in conjunction with brachytherapy appears to be a relatively safe and effective modality, but must be tested prospectively to compare its efficacy to interstitial irradiation alone.

Adult↗
PubMed1990

Two or six hyperthermia treatments as an adjunct to radiation therapy yield similar tumor responses: results of a randomized trial.

From March 1984 to February 1988, 70 patients with 179 separate treatment fields containing superficially located (less than 3 cm from surface) recurrent or metastatic malignancies were stratified based on tumor size, histology, and prior radiation therapy and enrolled in prospective randomized trials comparing two versus six hyperthermia treatments as an adjunct to standardized courses of radiation therapy. A total of 165 fields completed the combined hyperthermia-radiation therapy protocols and were evaluable for response. No statistically significant differences were observed between the two treatment arms with respect to tumor location; histology; initial tumor volume; patient age and pretreatment performance status; extent of prior radiation therapy, chemotherapy, hormonal therapy, or immunotherapy; or concurrent radiation therapy. The means for all fields of the averaged minimum, maximum, and average measured intratumoral temperatures were 40.2 degrees C, 44.8 degrees C, 42.5 degrees C, respectively, and did not differ significantly between the fields randomized to two or six hyperthermia treatments. The treatment was well tolerated with an acceptable level of complications. At 3 weeks after completion of therapy, complete disappearance of all measurable tumor was noted in 52% of the fields, greater than or equal to 50% tumor reduction was noted in 7% of the fields, less than 50% tumor reduction was noted in 21% of the fields, and continuing regression (monotonic regression to less than 50% of initial volume) was noted in 20% of the fields. No significant differences were noted in tumor responses at 3 weeks for fields randomized to two versus six hyperthermia treatments (p = 0.89). Cox regression analyses were performed to identify pretreatment or treatment parameters that correlated with duration of local control. Tumor histology, concurrent radiation doses, and tumor volume all correlated with duration of local control. The mean of the minimum intratumoral temperatures (less than 41 degrees C vs. greater than or equal to 41 degrees C) was of borderline prognostic significance in the univariate analysis, and added to the power of the best three covariate model. Neither the actual number of hyperthermia treatments administered nor the hyperthermia protocol group (two versus six treatments) correlated with duration of local control. The development of thermotolerance is postulated to be, at least in part, responsible for limiting the effectiveness of multiple closely spaced hyperthermia treatments.

Adult↗
PubMed1990

Effects of X irradiation on angiogenesis.

We have evaluated the effect of X irradiation on the mesenchymal tissue growth (blood capillaries and stromal cells) in an angiogenesis system in the mouse. This was accomplished by implanting a polyvinyl alcohol sponge disc in the subcutis of the thorax, and quantifying the extent of growth reduction of capillaries and stromal cells following graded doses of X rays. The sponge disc contained a centrally located pellet impregnated with 20 micrograms of epidermal growth factor and coated with a thin film of slow-releasing compound. Total growth of vessels and fibroblasts was determined by morphometric analysis of histologic sections. The incorporation of [3H]TdR was measured during a 24-h period. A dose-response relationship was observed when X irradiation was given on Day 11 after implantation, with the disc removed on Day 20. A single dose of 15 Gy reduced both the rate of incorporation of [3H]TdR and the total growth area. These and previous observations point to endothelial cells as important targets of ionizing radiation in the stroma, especially during the period of active proliferation of these cells, induced by growth factors.

Animals↗
PubMed1988

Bladder cooling in patients treated with regional hyperthermia of the pelvis using an annular phased array.

Regional hyperthermia for the treatment of deep seated tumors is often limited by excessive heating of normal tissues, usually with associated patient pain and/or discomfort. The use of bladder cooling via perfusion of distilled water through a modified tri-lumen irrigation catheter as an aid to circumventing this problem in one anatomical region is described. This relatively simple technique provided rapid pain relief and permitted completion of the hyperthermia treatment in a satisfactory manner. Modifications of this technique may permit selective heating and/or cooling of the bladder during regional hyperthermia treatments in the pelvis.

Adult↗
PubMed1988

Hyperthermia inhibits angiogenesis.

Since in vitro studies have demonstrated that capillary endothelial cells are thermosensitive, experiments were performed to determine the (in vivo) heat sensitivity of blood capillaries and their endothelial cells. Angiogenesis discs were implanted subcutaneously in mice, and vascular growth was stimulated by slow release of epidermal growth factor placed in the center of each disc. After 5 days of growth the discs were subjected to radiofrequency-induced hyperthermia. Heat exposures were 41, 42, 43, and 44 degrees C for 30 min. Control discs were sham treated. Seven days after heating the discs were extracted and paraffin embedded. Centripetal (radial) vessel growth was measured in magnified medial planar sections. An inverse relationship was demonstrated between vessel growth and exposure temperature. The extent of the fibroblastic growth was also inversely proportional to temperature. Thus, at least in this system, the microvasculature shows dose-dependent damage by hyperthermia, consistent with preceding in vitro observations. This inhibition of angiogenesis may result from endothelial cell killing, interference with cell replication, inhibition of cell migration, or a combination of these mechanisms.

Animals↗
PubMed1988

The disc angiogenesis system.

A new system for the study of angiogenesis in vivo has been devised. It consists of a small disc of polyvinyl alcohol foam, covered on both flat sides by Millipore filters, leaving only the edge as the area for cell penetration into the disc. Angiogenic agonists or antagonists, as well as other substances to be studied, are placed in the center of the disc. The slow release of these substances is maintained by a film of ethylene-vinyl acetate co-polymer, or by the use of agarose. The disc is implanted subcutaneously in the host animal through a distant skin incision. In mice, the optimal times for examination of the discs are 7 to 12 days after implantation for discs containing angiogenic stimulants and 12 to 20 days for those without stimulants. After a period of growth is completed, the disc is removed, fixed, and embedded in paraffin or methacrylate. Medial plane sections, stained by a variety of methods, are used to observe and measure the growth of vessels and stroma into the disc. Whether stimulated or not, this growth is centripetal and can be easily quantitated by simple morphometric technics. This system has already been used in mice, to study the proliferation of vessels and fibroblasts into discs devoid of, or containing angiogenic stimulants (epidermal growth factor, acidic fibroblastic growth factor). We have also utilized the discs to demonstrate the inhibition of vessel growth by hyperthermia. Examples of these applications are presented. The disc angiogenesis system is easy to prepare, inexpensive, and well tolerated, at least by mice. Its simplicity and reproducibility make it suitable for a wide range of applications beyond those described here.

Angiogenesis Inducing Agents↗
PubMed1985

Noninvasive thermometry using multiple-frequency-band radiometry: a feasibility study.

The potential use of multiple-frequency-band radiometry as a means of noninvasive sensing of one-dimensional temperature profiles is presented in this communication. The radiative energy transfer equation is solved numerically. Ideal-condition thermal noise spectra and distributions of received energy, associated with specific temperature-depth profiles, are presented. Performance characteristics are discussed.

Humans↗
PubMed1985

Thermal sensitivity to single and double heat treatments in normal canine liver.

The treatment of intrahepatic or perihepatic neoplasms by hyperthermia may be limited by the thermal sensitivity of normal liver tissue. To establish the temperature dependence of hepatic toxicity, eight canine liver lobes were exposed to a single 30-min dose of localized hyperthermia in the range of 43.0 degrees C-47.5 degrees C, induced by radiofrequency currents. Four additional liver lobes were conditioned with a pretreatment dose of 43.0 degrees C/30 min and challenged at either 44.5 degrees C/30 min or 47.5 degrees C/30 min, 4 h later. Temperature distributions were measured using implantable thermocouple sensors. Treated areas were sampled 28 days later, and liver damage was determined using histopathological criteria. Most treated sites showed only modest alterations. The parameters of tissue injury that correlated best with dose were: evidence of hepatocyte loss; focal fibrosis; and distortion of lobular architecture. Areas of necrosis were observed in several samples, but their presence or severity did not correlate with dose. Thermal damage to liver capsule, liver lobules, portal areas, and central veins did not exhibit monotonic dose-response relationships. The data do not demonstrate thermotolerance; in fact, they suggest, although do not prove, its absence. If thermotolerance did not develop, vascular effects might explain such a finding.

Animals↗
PubMed1983

The effects of hyperthermia on normal mesenchymal tissues. Application of a histologic grading system.

The alterations produced by radiofrequency-induced hyperthermia of 42 to 48 degrees C for 30 minutes were studied in the subcutaneous adipose tissue and skeletal muscle of swine. Acute lesions (18 to 24 hours) included edema, hemorrhage, necrosis (predominantly of myocytes) and granulocytic exudate in fat or muscle. The most important chronic lesion (28 to 31 days) was fibrosis replacing either tissue. There was a histiolymphocytic exudate with foreign-body giant cells around large lipid vacuoles. Muscle necrosis persisted and there was variable myocyte regeneration. Several specimens showed deep necrosis and abscesses. A grading system was developed to quantitate independently acute and chronic damage in each tissue. Acute lesions were usually less severe and extensive than chronic ones, without obvious dose response. Chronic lesions showed clearly a dose response, which began at 43 degrees C and increased with temperature. The latter appear to be reliable indicators of hyperthermic damage in deep soft tissues.

Adipose Tissue↗
PubMed1983

Thermal sensitivity and thermotolerance in normal porcine tissues.

We have previously presented a histopathological grading scheme for thermal damage in normal porcine adipose and skeletal muscle tissues. Here we have used this scheme to assess the heat sensitivity of these tissues, and evaluate the protective benefit of thermotolerance as induced by a prior thermal exposure. Tissues were exposed to temperatures ranging from 40-50 degrees for 30 min. Half of all sites also received a thermal exposure of 41.0-43.0 degrees 4 hr earlier. Biopsies for histological evaluation were obtained at 18 to 24 hr ("acute") and at 28 to 31 days ("chronic") following treatment. Only mild acute injury was seen in the early samples, following either single or double heat exposures, at all temperature levels. Minimal chronic damage was also seen in the late samples following single exposures of 45 degrees or less. Higher single exposures caused important chronic lesions, the severity of which was dose dependent. Regions that had received the earlier conditioning thermal exposure showed a significant protection against the subsequent thermal exposure. In such regions, mean (chronic) pathology scores were reduced by 76 to 86% over the temperature range 45-48 degrees. The degree of acute damage failed to predict the degree of chronic damage. Overall, induction of thermotolerance provided an advantage of 2 degrees or more in normal tissue protection.

Adipose Tissue↗
PubMedDate not supplied

Temperature distributions induced in pig tissues by a water-cooled disk electrode rf system.

Thermal dosimetry is one of the most challenging and necessary aspects of therapeutic hyperthermia. Treatment optimization and assessment of efficacy of the therapy can only be achieved by a quantification of the thermal distributions in normal and malignant tissue induced by specific configurations of heat sources. Radial and axial temperature distributions induced in normal porcine tissues by a pair of disk-shaped direct contact electrodes operating at 0.5 MHz are presented in this communication. Temperature increments induced in the skin, adipose tissue, and skeletal muscle tissue are correlated with the magnitude of the incident power density for various sizes of circular electrodes. The observed thermal distributions very likely relate to the heterogeneous thermal and electrical properties of these tissues.

Animals↗