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Biomedical subjects

F W Hetzel

Publications and source records attributed to F W Hetzel.

At least 55 records · Page 3Linked to original sources
PubMed1984

The synergistic effect of hyperthermia and chemotherapy on murine transitional cell carcinoma.

The in vivo effect of hyperthermia and chemotherapy was studied in a murine transitional cell carcinoma model. Localized hyperthermia (43.5C) of 60 and 90 minutes duration was combined with systemic doxorubicin hydrochloride, cis-platinum, cyclophosphamide or mitomycin to treat tumors implanted into the hind legs of C3H mice. The data were compared to the results obtained from the application of hyperthermia or chemotherapy alone as well as to the natural growth rate of untreated tumors. Untreated tumors grew with an exponential rate and had a doubling time of 4 +/- 1.5 days. Animals bearing such tumors survived for 25 +/- 7 days. When treated with hyperthermia alone, there was no significant reduction in the growth rate and no improvement was noted in the survival time. Treatment with doxorubicin hydrochloride, cyclophosphamide or mitomycin administered alone was likewise not effective. Cis-platinum alone was able to induce a minimal decrease in the growth rate. When the administration of chemotherapy was accompanied by hyperthermia, significant synergistic effect was noted for doxorubicin hydrochloride, cis-platinum and cyclophosphamide (p less than .01); only the mitomycin and hyperthermia combination failed to improve survival and decrease the growth rate. The duration of the hyperthermia exposure influenced the degree of tumor response. Hyperthermia of 90 minutes duration resulted in consistently greater decrease in tumor growth rate with doxorubicin hydrochloride, cis-platinum or cyclophosphamide than 60 minutes of hyperthermia combined with the same agents. These results indicate that local hyperthermia combined with doxorubicin hydrochloride, cis-platinum or cyclophosphamide can induce tumor regression, increase tumor doubling time and improve the survival of the tumor-bearing animal. Only the hyperthermia-mitomycin combination did not result in significant improvement from the baseline values. Thus, hyperthermia combined with selected chemotherapeutic agents can have an adjuvant effect in the treatment of established, implanted mouse bladder tumors.

Animals↗
PubMed1984

Effects of hematoporphyrin (HPD) and a chemiluminescence system on the growth of transplanted tumors in C3H/HeJ mice.

Photoradiation therapy is emerging as a promising technique for combating cancer. Fundamentally, this approach consists of two steps: hematoporphyrin derivative (HPD) is used to selectively sensitize cancer cells to visible light; after an appropriate time interval, light is introduced into the tumor via a laser-fiber optic system to trigger the cytotoxic action of HPD. The present investigation was initiated to determine the therapeutic potential of HPD in combination with a chemiluminescent activator in treating mice which had been transplanted with tumors.

Animals↗
PubMed1983

Chemotherapeutic drugs as indirect oxygen radiosensitizer.

We have characterized the oxygen distribution in V-79 spheroids which were grown by the spinner flask method. Using ultramicroelectrodes with tip diameters of 1-5 microns and a perfusion system whereby the spheroids' milieu could be maintained and controlled, we found plateau pO2 values of less than 10 mm Hg in spheroids of greater than 500 microns in diameter. Data from experiments using respiration inhibitory drugs indicate that the characteristics of the outer layers of cells is the major determinant of the oxygen profile in the interior. Parallel control radiobiological experiments confirmed the control pO2 measurements, and formed the basis for the experiments using the potential indirect radiation sensitizers: Chlorambucil and Mustargen.

Animals↗
PubMed1982

Results of a phase I/II clinical trial of fractionated hyperthermia in combination with low dose ionizing radiation.

This paper addresses, in part, the current status of hyperthermia as a new clinical modality and reports the results of a large, prospective clinical trial employing microwave hyperthermia in combination with low doses of ionizing radiation. In the protocol employed, each treated area received 8 hyperthermia treatments of 1.5 hour combined with 1600 rad over a total period of 5 weeks. Patients were heated with microwaves of 915 or 300 MHz employing external applicators or internal intracavitary antennas. The results of this fractionation scheme are encouraging since in 121 fields that were treated completely according to protocol and were available for follow-up for at least 2 months, complete responses were observed in 65% of all cases, partial response in 30% and no response in only 5%. It is also important to note that toxicity was minimal throughout the study.

Clinical Trials as Topic↗
PubMed1981

Radiation sensitivity modification by chemotherapeutic agents.

Three chemotherapeutic agents, chlorambucil, mustargen, and BCNU-409962, being investigated for their possible clinical use in conjunction with radiation therapy have been shown in vitro to dramatically affect the characteristics of standard radiation survival curves (in V79 cells and spheroids). The agent mustargen, at a concentration of 0.25 microgram/ml administered 1 hour prior to 9-MeV-electron exposure, had a significant effect in reducing D0. The 165-rad D0 observed in control curves was reduced to 105 rads in the presence of drug. One hour preincubation with BCNU (prior to radiation exposure) at a concentration of 3.0 microgram/ml was found to dramatically reduce the initial shoulder region with n number values for drug curves approximately one-half those seen for controls. No effect is seen when chlorambucil is combined with radiation in exponential or confluent cultures but an enhancement ratio of 1.8 is found when intact spheroids are pretreated with this drug.

Animals↗
PubMed1981

A system for determining the pharmacology of indirect radiation sensitizer drugs on multicellular spheroids.

We have characterized some of the physiology of multicellular spheroids of different sizes grown from Chinese hamster lung fibroblast (V79) cells. Among the parameters studied were oxygen tension distributions within the spheroid. This was achieved using ultramicroelectrodes with tip diameters of 1-5 mu and a perfusion system whereby environmental conditions such as flow, temperature, and chemical makeup of the milieu could be measured and controlled. Plateau pO2 values of less than 10 mm Hg were consistently obtained from spheroids under various conditions. We were able to modify these distributions by use of indirect radiation sensitizer drugs such as mechlorethamine HCl (mustargen) at nontoxic doses. We have also made determinations of the inhibitory capacities of several other drugs on the respiration rate of constituent cells of multicellular spheroids in single-cell suspensions. We have concluded that there are indeed hypoxic cells in spheroids whose radioresistance may be modified by essentially nontoxic levels of indirect radiosensitizer drugs and that the system described shows great promise for screening agents which may modify radiation response.

Animals↗
PubMed1980

Effects of hyperthermia on normal and tumor microenvironment.

The effects of hyperthermia on pH, local blood flow (LBF) and tissue oxygen tension (TpO2) in several normal and tumor tissues were studied. It was found that TpO2, local blood flow and pH are inhomogeneous in tumor tissue. TpO2 is very low in certain areas which also seem deprived of blood flow and are at very low pH. Hyperthermia has a dual effect: at temperatures below 41 degrees C, it increases blood flow and TpO2 while above 41 degrees C, it causes a collapse in blood flow, lower TpO2 and a shift of the tissue pH towards acidosis from the already low pH values found in tumors.

Adenocarcinoma↗
PubMed1978

The demonstration of in vivo misonidazole tumour toxicity using post radiation hypoxia.

The cytotoxic effect of the radiosensitizer misonidazole on hypoxic tumour cells in vivo has been studied. Using standard procedures of large single doses of X-ray (30 Gy) followed by 1.0 mg/g misonidazole, no significant cytotoxicity (measured by tumour regrowth) could be observed. In contrast, when utilizing post radiation hypoxia (3 h of 7% oxygen breathing) in conjunction with post radiation misonidazole, an increased amount of direct drug toxicity was demonstrated. The use of this acute hypoxia treatment may prove to be a useful tool for measuring various in vivo radiobiological responses.

Animals↗
PubMed1977

The effects of vasopressin on the radiation response of cultured mammalian cells.

Since vasopressin is known to exert radioprotective effects in vivo, its effects on mammalian cells in vitro were examined. No toxicity or changes in cellular plating efficiency were observed at concentrations up to 10 units/ml. There was no direct radioprotective effect attributable to exposure of the cells to vasopressin prior to and during irradiation.

Animals↗