Effects of microwave-induced local hyperthermia on mammary adenocarcinoma in C3H mice.

Microwave-induced hyperthermia was focused locally upon mammary adenocarcinoma implanted in C3H mice when the tumor reached 6 mm in diameter. In 54 treated mice, all tumors diminished in size after the first exposure (43 degrees, 45 min) and disappeared completely following the second treatment. No other effects from heat application were apparent. All the mice in the microwave-treated group survived the whole period of observation (4 months) without any evidence of tumor, while 18 nontreated controls died within 4 weeks after inoculation.

The effect of dead cells on the activity of actinomycin D against mouse sarcoma 180 ascites.

It has been demonstrated that cells killed by heat or irradiation have four times greater affinity for actinomycin D (AMD) than do viable tumor cells. By using a double labeling technique, we were able to show that, with increasing amounts of AMD bound in cells, the incorporation of RNA precursors is proportionally decreased. However, in the presence of nonviable cells or of native DNA, the AMD-induced inhibition of [3H]uridine incorporation is markedly reduced. This reduction does not occur if DNase is added to the system. The accumulation of dead cells in the tumor vicinity during the natural course of tumor growth or therapy must be taken into consideration in planning therapeutic regimens. We suggest that, in combined chemo- and radiotherapy, increased effectiveness of AMD may be obtained by its use prior to irradiation, thereby assuring its direct access to the tumor cells. The addition of DNase could eliminate or greatly diminish the dead cell competition for the drug.

Flow-microfluorometric analysis of nuclei isolated from various normal and malignant human epithelial tissues. A preliminary report.

In order to obviate some of the technical problems associated with preparation of monocellular cell suspensions required for flow fluorometry, isolation of nuclei from several types of benign and malignant human tissues was undertaken. Satisfactory preparations of nuclei were obtained from epithelia of the uterine cervix and colon and from lung tissue using the citric acid method. The sucrose method was effective with colonic epithelium only. Distribution of deoxyribonucleic acid content in these nuclei was measured based on green fluorescence of acridine orange and red fluorescence of propidium iodide in a Bio-Physics Cytofluorograph. Essentially diploid patterns of deoxyribonucleic acid distribution were observed for all benign samples regardless of tissue origin whereas the malignant samples gave histograms suggestive of abnormal deoxyribonucleic acid distribution. Preliminary observations on distribution of single-stranded nucleic acids using acridine orange red fluorescence showed marked differences between populations of benign and malignant nuclei. Isolated nuclei appear to be suitable for flow-through microfluorometric analysis and offer some significant advantages over intact cells.

A polynucleotide segment rich in adenylic acid in the rapidly-labeled polyribosomal RNA component of mouse sarcoma 180 ascites cells.

The rapidly-labeled polyribosomal RNA component from mouse sarcoma 180 cells is retained on nitrocellulose (Millipore) membrane-filters at high ionic strength. This property is due to the presence of a polynucleotide sequence rich in adenylic acid that resists both T(1) and pancreatic RNase digestion. The resistant material shows sedimentation characteristics close to those of transfer RNA. The RNA molecules that contain this material can be separated from the rest of the polysomal RNA by differential phenol extraction with neutral and alkaline Tris buffers. Synthetic poly(A) exhibits the same behavior as the rapidly-labeled polysomal RNA with respect to Millipore binding and phenol fractionation. The characteristics of the rapidly-labeled polysomal RNA component permit its isolation free of ribosomal RNA.

Some practical considerations for the use of localized hyperthermia in the treatment of cancer.

Practical considerations in the selection and administration of microwave and RF induced hyperthermia in the treatment of various tumors are discussed. A thorough knowledge of the thermal properties of the tumor and its environment is required for the establishment of an effective therapeutic regimen. Examples of clinical observations illustrate the patients' general tolerance to the therapy and highlight the problems presented by some special cases. Possible ways of avoiding adverse effects during localized microwave induce heating of superficial tumors and RF heating of deep seated tumors are described.

Therapeutic potential of conformal applicators for induction of hyperthermia.

One of the basic requirements for effective use of hyperthermia in treatment of cancer is the delivery of uniform heat to specific volumes of tissues and maintenance of the optimal temperature for an appropriate period of time. Preliminary results of temperature distribution in volumes of tissue placed between two conformal applicators energized at 2.45 GHz are presented. The applicators consist of a jointed-circuit antenna array comprising a multiplicity of dipoles backed by a metal cavity filled with a powder of high dielectric constant, and separated from the treatment area by a "beanbag" filled with the same powder. Uniform heating could be achieved in a tissue mass confined between two applicators placed 5 cm apart.

Supplemental vitamin A prevents the tumor-induced defect in wound healing.

To test our hypothesis that supplemental vitamin A would mitigate the impaired healing that occurs in tumor-bearing animals, six groups of C3H mice, eight per group, eating a standard commercial mouse chow ad libitum that supports normal growth, reproduction, and longevity were innoculated with 200,000 C3HBA cells. When tumors measured approximately 6 mm in diameter, the mice were anesthesized and wounded (dorsal skin incisions and subcutaneous polyvinyl alcohol sponges). Twenty-four hours later, two groups (one continued on the chow and the other started on the chow supplemented with 150,000 IU vitamin A/kg chow) underwent local tumor irradiation; two groups, one ingesting the chow, the other the vitamin A supplemented chow, were started on cyclophosphamide therapy; two groups, one ingesting the chow, the other the vitamin A supplemented chow, received neither local tumor irradiation nor cyclophosphamide therapy. An additional two groups ingesting the chow, one group neither innoculated with tumor nor wounded, the other wounded by not innoculated, served as controls. Wound breaking strength and sponge reparative collagen accumulation (assessed by hydroxyproline proline measurement) were used as indicators of wound healing. The mice were killed 12 days after wounding. Tumor presence decreased wound breaking strength and sponge hydroxyproline content; these effects were largely negated by supplemental vitamin A. Local tumor irradiation diminished the adverse effect of tumor on sponge reparative collagen content but to a lesser extent than the supplemental vitamin A. Supplemental vitamin A added to the irradiation effect on healing but irradiation did not add to the vitamin A effect. Cyclophosphamide, a systemic radiomimetic anti-tumor agent, did not alter the impaired wound healing of the tumor-bearing mice. Supplemental vitamin A mitigated the impaired wound healing in the cyclophosphamide-treated tumor-bearing mice. Supplemental vitamin A also moderated the effects of wounding, tumor, and tumor therapies (local irradiation and cyclophosphamide) on the increase in adrenal size, leukopenia, thrombocytopenia, and thymic involution (except the last was not moderated in the cyclophosphamide-treated tumor-bearing rats). The splenic enlargement in the untreated tumor-bearing wounded rats and in those treated with cyclophosphamide was lessened by supplemental vitamin A. We hypothesize that these anti-stress effects of vitamin A underlie, in part, its action in mitigating the impaired wound healing of tumor-bearing mice, including those treated by local irradiation or cyclophosphamide. These findings have implications for the care of patients with malignant tumors.