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Cytogenetic studies were performed on a fibrosarcoma of a newborn. Only numerical chromosome changes (+8, +11, +20) were identified in this rare but distinct soft tissue sarcoma that occurs in children less than 5 years old.
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Azathioprine (AZ) was injected into C57 Black mice before or after IM implantation of the syngeneic fibrosarcoma FS6, and observations were made on tumour growth and on the cellular composition of the fibrosarcomas. When multiple injections were given to the tumour-bearing host the tumours regressed. The percentage of tumour-associated macrophages remained essentially stable as regression occurred whereas the percentage of theta-antigen-positive cells increased. In the case of single IP injections of AZ, changes in the cellular composition of tumours were seen only when AZ was given 1-72 h before implantation but not when it was given after implantation. Compared with controls there was a 2- to 3-week delay in the appearance of large numbers of tumour-associated macrophages. The percentage of theta-antigen-positive cells within the tumours mass was elevated 7 days post AZ treatment but the level declined to control values between days 10 and 13. The significance of the results is discussed in relation to the dependency of the macrophage content of this tumour upon the development of an immune response towards the tumour.
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The effect of Bacillus Calmette-Guérin cell wall skeleton (BCG-CWS), which is one of the well-established immunopotentiators, on the induction of either cytotoxic or suppressor T cells against syngeneic tumor S1509a was investigated by an in vitro assay system. BCG-CWS showed an apparent augmenting activity in the induction of cytotoxic T cells against a syngeneic tumor when it was administered subcutaneously into mice with mitomycin C (MMC)-treated tumor cells in a form of oil-in-water emulsion. In addition, cytotoxic T cell activity was dominantly generated in regional lymph nodes. Furthermore, the immunized animals developed stronger resistance against the second inoculum of the same viable tumor cells. However, BCG-CWS had no effect on the induction of suppressor T cells in tumor-bearing host (TBH), and could not induce cytotoxic T cells against the homologous tumor in TBH in which suppressor T cells had been rapidly activated. The growth of tumor was neither suppressor nor enhanced, even if an oil-attached BCG-CWS was administered in TBH.
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"Pregnancy-specific" beta-1 glycoprotein (SP1) was produced in vitro by nine of 32 established cell lines derived from human malignant neoplasms. The nine positive lines comprised a variety of cell types, and SP1 production ranged from 0.36 to 35.5 pmol/mg cell protein at confluence. The highest production was by a fibrosarcoma line. SP1 in medium and cells from this line was indistinguishable immunochemically and gel chromatographically from purified (Bohn) placental SP1. None of the SP1-positive lines produced placental lactogen, only three produced the alpha subunit of chorionic gonadotropin (CG), and only four produced the beta subunit of CG. SP1-positive lines that produced cg-alpha did not produce CG-beta. Secretion of SP1 and of CG-beta by the fibrosarcoma line followed different time courses.
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Ethanolamine plasmalogens (1-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamines) of many tissues contain high levels of arachidonate at their 2-position, and in certain tissues have been implicated as possible donors of arachidonate required in the synthesis of prostaglandins and thromboxanes. In the present study, [3H]arachidonate-labeled phospholipids of HSDM1C1 cells, a cell line derived from a mouse fibrosarcoma, were examined to determine the donor of the arachidonic acid released upon bradykinin stimulation of the synthesis of PGE2. HSDM1C1 cells labeled with [3H]arachidonic acid for 24 hr in serum-free medium were used in most of the experiments and had the following distribution of label among the cellular lipids; phosphatidylcholine (33%), phosphatidylinositol (20%), diacyl-sn-glycero-3-phosphoethanolamine (15%), ethanolamine plasmalogen (15%), and less polar lipids )16%). Bradykinin treatment stimulated a rapid hydrolysis of [3H]arachidonate from the cellular lipids and conversion of the released acid to PGE2, which was secreted into the medium. The label was released predominantly from phosphatidylinositol and possibly from phosphatidylcholine with no detectable change in the labeling of diacyl- or 1-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamine. The ethanolamine plasmalogens, therefore, do not appear to be involved in the stimulated release of arachidonate in the HSDM1C1 cells. Indomethacin blocked the bradykinin-stimulated synthesis of PGE2 and to a lesser degree inhibited the release of [3H]arachidonate from the cellular lipids into the medium.
We have examined the effects on platelet function of two sublines (M4 and M9) derived from spontaneous lung nodules of a benzopyrene-induced murine fibrosarcoma (m FS6). The subline M4 was more metastatic and the subline M9 less metastatic than the primary tumour. Only the more malignant cells were able to induce irreversible aggregation of human platelets; this effect was concentration-dependent and was associated with the release of serotonin by platelets. Both aggregation and release were inhibited by preincubation of platelets with ASA, not by preincubation of the cells. The supernatants of cell suspensions had no aggregating activity. However, the neoplastic cells in culture media released an activity directly stimulating platelet aggregation and potentiating the platelet response to ADP; again, this activity was higher for the more malignant cells and the effects were inhibited by preincubation of platelets with ASA. These results suggest a role for platelets in the development of tumour metastases.
A system for applying local hyperthermia employing ultrasonic transducers with annular focusing lenses gave better temperature uniformity in small fibrosarcomas than conventional unfocused transducers. The lenses were designed for ultrasonic frequencies of 3, 4, 5 and 9 MHz for tumors approximately 6 mm dia. Tests in degassed water indicated that the focusing lenses concentrated approx. 80% of the ultrasonic energy into an annular-shaped focus of 6 mm dia. located at a distance of 3 cm in front of the lens. These transducers were used to heat subcutaneous PARA-7 fibrosarcomas in hamsters. Steady-state temperature measurements indicated temperature gradients within tumors of 0.5-1.0 degree C when transducers employing annular-focused lenses were used, versus gradients of 2.0-2.3 degree C with 10 mm dia. unfocused transducers.
The effects of different sources of protein (milk, soy, wheat, fish and beef), fat (corn oil and butter), and carbohydrate (dextrin and sucrose) on tumor development and on spleen characteristics were investigated in BALB/c mice injected subcutaneously with 5 X 10(5) herpes simplex virus Type 2-transformed cells (H238 cells). Low or high levels of protein and fat were used. Several weeks post-injection results indicated that a high level of fat significantly enhanced tumor incidence. A high fat level was also associated with a lower spleen weight and a smaller proportion of mature granulocytes in the spleen. Butter, compared to corn oil, significantly restricted tumor volume. Among the most highly significant findings was the low tumor incidence in mice fed protein from either a milk or a fish source.
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PURPOSE: This study investigated the effect of timing and sequence of hyperthermia on fractionated radiotherapy, since it has been shown that the heat increases the size of hypoxic cell fraction which could affect the effect of subsequent radiation doses. METHODS AND MATERIALS: Animal-tumors were early generation isotransplants of a spontaneous fibrosarcoma, FSa-II, in C3Hf/Sed mice. Tumor response was studied by tumor growth time and TCD50 (50% tumor control dose) assays. The tumor growth time is the time required for one-half of the treated tumors to reach 500 mm3 from the first treatment day. The TCD50 is a radiation dose to control one-half of the treated tumors for 120 days following treatments. One heat treatment at 43.5 degrees C for 45 min was given in a water bath in combination with fractionated doses independently (24 hr interval) or simultaneously (2 min interval). For the normal tissue study, the mouse foot was treated, and the acute foot reaction was scored daily and averaged. The late foot reaction was scored in animals used in the TCD50 assay that developed no recurrence for 120 days. The RD50(2.0) and RD50(5.0), or total radiation doses to induce an average score of 2.0 (complete epilation) and 5.0 (partial foot atrophy) in 50% of treated animals, were calculated. RESULTS: Thermal radiosensitization was most prominent when heat was combined simultaneously with the first or last radiation dose in both the tumor growth time and TCD50 assays. However, the thermal enhancement was greatest when heat was given either with the first or last radiation dose in the TCD50 assay; whereas it was greatest when heat was administered with the last radiation dose in the tumor growth time assay. Both acute and late skin reactions were significantly potentiated by heat administered 24 hr before the first radiation dose. CONCLUSION: A significant observation in this study was that, in both the tumor growth time and TCD50 assays, heat given independently or simultaneously did not result in any therapeutic gain compared to the radiation alone treatment.
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The growth of tumours in guinea-pigs was observed for 20 weeks after placing them on various doses of vitamin C. Complete tumour regression occurred in 55% of those animals receiving 0-3 mg/kg/day ascorbic acid, whereas animals given 10 mg/kg/day showed tumour inhibition but no regression. In contrast, tumours in animals maintained on 1 g/kg/day ascorbic acid grew without sign of retardation. When increased amounts of ascorbic acid were restored to the diet of scorbutic tumour-bearing animals, tumours which had not regressed responded with enhanced growth. Likewise, animals previously maintained on 10 mg/kg ascorbic acid responded in turn to the additional vitamin with enhanced tumour growth. In contrast, all tumour-bearing animals maintained on 1 g/kh ascorbic acid died within 3 weeks when this dose was replaced with 0-3 mg/kg.