Chemopreventive property of Trichosanthes dioica root against 3-methylcholanthrene-induced carcinogenesis in albino mice.

This work reports the chemopreventive property of hydroalcoholic extract of the Trichosanthes dioica root (TDA) against 3-methylcholanthrene (3-MC)-induced carcinogenesis in Swiss albino mice. TDA was administered orally at 2 and 4 mg/kg for 45 days after 24 hours of a single subcutaneous administration of 3-MC (200 µg) in mice. The mice were observed for 15 weeks to record tumor incidence (fibrosarcoma) and survival. After 15 weeks the mice were killed for the evaluation of hematological profiles and hepatic biochemical parameters viz lipid peroxidation, reduced glutathione, glutathione-S-transferase, superoxide dismutase, and catalase. TDA treatment markedly reduced tumor incidence and prolonged the life span of sarcoma-bearing mice compared with 3-MC control mice. Hematological profiles of TDA-treated mice were restored significantly to normal levels. TDA treatment significantly modulated the liver biochemical parameters compared with 3-MC control. Therefore, TDA possesses remarkable cancer chemopreventive efficacy plausibly mediated by multiple mechanisms in Swiss albino mice.

Congenital fibrosarcoma and history of prenatal exposure to petroleum derivatives.

Congenital fibrosarcoma (CFS) is a rare fibrous tissue malignancy that usually presents in the first few years of life. It is unique among human sarcomas in that it has an excellent prognosis. We describe a temporal clustering of a number of cases of CFS and investigate the possible associated prenatal risk factors. The Pediatric Environmental History, a questionnaire developed in our clinic that is instrumental in determining environmental risk factors for tumor-related disease, was essential in documenting the presence or absence of risk factors considered as human carcinogens. We found a history of exposure to petroleum products in four cases of CFS that occurred at a greater than expected rate in a short time frame-an apparent cancer cluster. We call attention to the possibility that exposure to petroleum products raises the risk of developing CFS. While future studies should focus on systematic investigation of CFS and its underlying mechanisms, this report suggests the need for proactive measures to avoid exposure to solvents and petroleum products during pregnancy.

Evaluation of radiogallium-labeled, folate-embedded superparamagnetic nanoparticles in fibrosarcoma-bearing mice.

CONTEXT: Elevated expression of the folate receptor (FR) occurs in many human malignancies. Thus, folate targeting is widely utilized in drug delivery purposes specially using nano-radioactive agents. AIMS: In this work, we report production and biological evaluation of gallium-67 labeled superparamagnetic iron oxide nanoparticles, embedded by folic acid ( 67 Ga-SPION-folate) complex especially in tumor-bearing mice for tumor imaging studies. SETTINGS AND DESIGN: The structure of SPION-folate was confirmed by X-ray diffraction (XRD), transmission electron microscopy (TEM) and foureir transform infrared spectroscopy (FT-IR) analyses. The radiolabeled SPION-folate formation was confirmed by instant thin layer chromatography (ITLC). Tumor induction was performed by the use of poly-aromatic hydrocarbon injection in rodents as reported previously. MATERIALS AND METHODS: [ 67 Ga]-SPION-folate was shown to possess a particle size of ≈ 5-10 nm using instrumental methods followed by ITLC test. Biocompatibility of the compound was investigated using an 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay followed by stability tests and tumor accumulation studies in fibrosarcoma-bearing mice after subcutaneous (s.c.) application. STATISTICAL ANALYSIS USED: All values were expressed as mean ± standard deviation (mean ± SD) and the data were compared using Student t-test. Statistical significance was defined as P<0.05. RESULTS: [ 67 Ga]-SPION-folate was prepared by a modified co-precipitation method possessing a particle size of ≈ 5-10 nm using instrumental methods (>95% radiochemical purity). Biodistribution studies demonstrated tumor:blood, tumor:bone and tumor:muscle ratios of 4.23, 4.98 and 11.54 respectively after 24 h. CONCLUSIONS: Due to the nano-scale size and high-penetrative property of the developed folate-containing nano-complex, this system can be an interesting drug delivery modality with therapeutic applications and folate receptor-targeting behavior, while possessing paramagnetic properties for thermotherapy.

Development of a quantitative bioassay to assess preventive compounds against inflammation-based carcinogenesis.

Reducing cancer incidence and mortality by use of cancer-chemopreventive agents is an important goal. We have established an in vitro bioassay that is able to screen large numbers of candidate chemicals that are positive for prevention of inflammation-related carcinogenesis. To accomplish this we have added candidate chemicals or vehicles and freshly isolated, fluorescent dye-labeled inflammatory cells that were overlaid on TNF-alpha-stimulated mouse endothelial cells in a 96-well plate. Inhibition of inflammatory cell attachment to the endothelial cells by the chemicals was quantified by the intensity of fluorescence from the adherent inflammatory cells after removing unattached cells. Using this assay, we selected two chemicals, auraptene and turmerones, for further study. As an in vivo test, diets containing these test chemicals were administered to mice with a piece of foreign body, gelatin sponge, that had been implanted to cause inflammation, and we found that the number of inflammatory cells that infiltrated into the subcutaneously implanted gelatin sponge was reduced compared to that found in the mice fed with a control diet. Moreover, diets containing either of the two chemicals prevented inflammation-based carcinogenesis in a mouse model. We found that the compounds reduced not only the number of infiltrating cells but also the expression of inducible nitric oxide synthase (iNOS) or formation of 8-hydroxy-2'-deoxyguanine (8-OHdG) in the infiltrated cells. Moreover, both compounds but not controls sustained the reducing activity in the inflammatory lesion, and this finding was confirmed by using non-invasive in vivo electron spin resonance. The newly established in vitro screening assay will be useful for finding biologically effective chemopreventive agents against inflammation-related carcinogenesis.

Targeted delivery of chemotherapeutic agents using improved radiosensitive liquid core microcapsules and assessment of their antitumor effect.

PURPOSE: Radiation-sensitive microcapsules composed of alginate and hyaluronic acid are being developed. We report the development of improved microcapsules that were prepared using calcium- and yttrium-induced polymerization. We previously reported on the combined antitumor effect of carboplatin-containing microcapsules and radiotherapy. METHODS AND MATERIALS: We mixed a 0.1% (wt/vol) solution of hyaluronic acid with a 0.2% alginate solution. Carboplatin (l mg) and indocyanine green (12.5 microg) were added to this mixture, and the resultant material was used for capsule preparation. The capsules were prepared by spraying the material into a mixture containing a 4.34% CaCl(2) solution supplemented with 0-0.01% yttrium. These capsules were irradiated with single doses of 0.5, 1.0, 1.5, or 2 Gy (60)Co gamma-rays. Immediately after irradiation, the frequency of microcapsule decomposition was determined using a microparticle-induced X-ray emission camera. The amount of core content released was estimated by particle-induced X-ray emission and colorimetric analysis with 0.25% indocyanine green. The antitumor effect of the combined therapy was determined by monitoring its effects on the diameter of an inoculated Meth A fibrosarcoma. RESULTS: Microcapsules that had been polymerized using a 4.34% CaCl(2) solution supplemented with 5.0 x 10(-3)% (10(-3)% meant or 10%(-3)) yttrium exhibited the maximal decomposition, and the optimal release of core content occurred after 2-Gy irradiation. The microcapsules exhibited a synergistic antitumor effect combined with 2-Gy irradiation and were associated with reduced adverse effects. CONCLUSION: The results of our study have shown that our liquid core microcapsules can be used in radiotherapy for targeted delivery of chemotherapeutic agents.

Defining a noncarcinogenic dose of recombinant human parathyroid hormone 1-84 in a 2-year study in Fischer 344 rats.

The carcinogenic potential of human parathyroid hormone 1-84 (PTH) was assessed by daily subcutaneous injection (0, 10, 50, 150 microg/kg/day) for 2 years in Fischer 344 rats. Histopathological analyses were conducted on the standard set of soft tissues, tissues with macroscopic abnormalities, selected bones, and bones with abnormalities identified radiographically. All PTH doses caused widespread osteosclerosis and significant, dose-dependent increases in femoral and vertebral bone mineral content and density. In the mid-and high-dose groups, proliferative changes in bone increased with dose. Osteosarcoma was the most common change, followed by focal osteoblast hyperplasia, osteoblastoma, osteoma and skeletal fibrosarcoma. The incidence of bone neoplasms was comparable in control and low-dose groups providing a noncarcinogenic dose for PTH of 10 microg/kg/day at a systemic exposure to PTH that is 4.6-fold higher than for a 100 microg dose in humans. The ability of PTH to interact with and balance the effects of both the PTH-1 receptor and the putative C-terminal PTH receptor, may lead to the lower carcinogenic potential observed with PTH than reported previously for teriparatide.

Inhibition of benzo(a)pyrene-induced carcinogenesis by vitamin C alone and by vitamin C/vitamin E and selenium/glutathione.

The reduction on peroxidation caused by benzopyrenes by some naturally occurring antineoplastic agents was studied in this experimental work. Inhibition/reduction of experimental carcinogenesis induced by benzo(a)pyrene by vitamin C alone and by vitamin C/vitamin E and selenium/ glutathione was attempted in 224 female Wistar rats divided in four groups. Injected with 10.08 mL benzo(a)pyrene, the animals were treated with some naturally occurring substances like vitamin C alone and a combination of anticarcinogens. By calculating the carcinogenic potency of benzo(a)pyrene and the anticarcinogenic potency of substances used as well as histological examination of developed tumors and survival time of treated animals, it was found that vitamin C exerts a significant anticarcinogenic effect of 8.3 units and that the combination of the two anticarcinogens used produced a significant prolongation of the animals survival time with anticarcinogenic potency of 22.1 and 22.2 units, respectively. This is considered a potent anticarcinogenic effect. The question of an additional supportive administration of such agents complementary to the conventional cancer chemotherapy in humans is raised. Of course, further studies are needed.

Enhancement of anti-cancer immunity by a lipoteichoic-acid-related molecule isolated from a penicillin-killed group A Streptococcus.

We isolated the lipoteichoic-acid-related molecule (OK-PSA) from OK-432, a streptococcal preparation, by affinity chromatography on CNBr-activated Sepharose-4B-bound monoclonal antibody TS-2, which neutralizes the interferon (IFN)-gamma-inducing activity of OK-432. We have previously reported that OK-PSA is a potent inducer of Th1-type cytokines in human peripheral blood mononuclear cells in vitro. In this study, we conducted an animal experiment to examine whether OK-PSA exhibits an anti-tumor effect in vivo by acting as a Th1 inducer in syngeneic Meth-A tumor-bearing BALB/c mice, in which the Th2 response is genetically dominant. It was found that OK-PSA induced Th1-type cytokines [IFN-gamma, tumor necrosis factor-alpha, interleukin (IL)-2, IL-12 and IL-18] in BALB/c mice bearing Meth-A tumor and caused a marked anti-tumor effect. Although it was suggested by an in vitro study. using spleen cells derived from the animals, that IL-18 plays the greatest role in the induction of the Th1-dominant state and tumor cell killing induced by OK-PSA, the in vivo experiments demonstrated that both IL-12 and IL-18 are essential in the anti-tumor effect exhibited by OK-PSA. These findings strongly suggest that OK-PSA is a major effector molecule of OK-432 and may be a useful immunotherapeutic agent, as a potent Th1 inducer, for cancer patients with a Th2-dominant state.

Chemopreventive activity of Withania somnifera in experimentally induced fibrosarcoma tumours in Swiss albino mice.

The current experimental work deals with the chemopreventive studies of a hydroalcoholic extract of Withania somnifera roots, against 20-methylcholanthrene induced fibrosarcoma tumours in Swiss albino mice. A single subcutaneous injection of 200 microg 20-methylcholanthrene in 0.1 mL of dimethylsulphoxide into the thigh region of mice produced a high incidence (96%) of tumours. Oral treatment of animals with 400 mg/kg body weight of Withania somnifera extract (one week before injecting 20-methylcholanthrene and continued until 15 weeks thereafter) significantly reduced the tumour incidence, tumour volume and enhanced the survival of the mice, compared with 20-methylcholanthrene injected mice. The tumour incidence was also delayed in the treatment group when compared with 20-methylcholanthrene injected mice. Liver biochemical parameters revealed a significant modulation of reduced glutathione, lipid peroxides, glutathione-S-transferase, catalase and superoxide dismutase in extract treated mice compared with 20-methylcholanthrene injected mice. The mechanism of chemopreventive activity of Withania somnifera extract may be due to its antioxidant and detoxifying properties.

Chemopreventive activity of Ocimum sanctum seed oil.

The seed oil of Ocimum sanctum was evaluated for chemopreventive activity against subcutaneously injected 20-methylcholanthrene induced-fibrosarcoma tumors in the thigh region of Swiss albino mice. Supplementation of maximal tolerated dose (100 microl/kg body weight) of the oil significantly reduced 20-methylcholanthrene induced tumor incidence and tumor volume. The enhanced survival rate and delay in tumor incidence was observed in seed oil supplemented mice. Liver enzymatic (superoxide dismutase, catalase, glutathione-S-transferase), non-enzymatic antioxidants (reduced glutathione) and lipid peroxidation end product, malondialdehyde levels were significantly modulated with oil treatment as compared to untreated 20-methylcholanthrene injected mice. The results of this study suggest that the potential chemopreventive activity of the oil is partly attributable to its antioxidant properties. The chemopreventive efficacy of 100 microl/kg seed oil was comparable to that of 80 mg/kg of vitamin E.

Effect of Withania somnifera on 20-methylcholanthrene induced fibrosarcoma.

Administration of an extract from the root of the plant Withania somnifera (20mg/dose/animal i.p) was found to inhibit the 20-methylcholanthrene induced sarcoma development in mice and increase the life span of tumour bearing animals. Administration of Withania could inhibit the lipid peroxide formation (152 nanomoles/mg protein) (P<0.01) compared with control (198 nanomoles/mg protein). Withania could increase the GSH level (7.7 micromoles/mg protein) which was lowered in control tumour bearing animals (3.96 micromoles/mg protein). GST level was also significantly increased (451 micromoles/min/mg protein) (P<0.001) in Withania treated animals compared to control animals (205 micromoles/min/mg protein). All the animals in the control group developed sarcoma by the 80th day of carcinogen administration. Only 3 animals in the Withania treated group developed sarcoma by the 105th day. In control animals the survival rate was 40% but in the Withania treated group the survival rate was 100% after 15 weeks of carcinogen treatment. These results indicate that Withania could inhibit 20-methylcholanthrene induced sarcoma development in mice.

Antitumor activity of astaxanthin and its mode of action.

Astaxanthin, a carotenoid without vitamin A activity, may exert antitumor activity through the enhancement of immune responses. Here, we determined the effects of dietary astaxanthin on tumor growth and tumor immunity against transplantable methylcholanthrene-induced fibrosarcoma (Meth-A tumor) cells. These tumor cells express a tumor antigen that induces T cell-mediated immune responses in syngenic mice. BALB/c mice were fed astaxanthin (0.02%, 40 micrograms/kg body wt/day in a beadlet form) mixed in a chemically defined diet starting zero, one, and three weeks before subcutaneous inoculation with tumor cells (3 x 10(5) cells, 2 times the minimal tumorigenic dose). Three weeks after inoculation, tumor size and weight were determined. We also determined cytotoxic T lymphocyte (CTL) activity and interferon-gamma (IFN-gamma) production by tumor-draining lymph node (TDLN) and spleen cells by restimulating cells with Meth-A tumor cells in culture. The astaxanthin-fed mice had significantly lower tumor size and weight than controls when supplementation was started one and three weeks before tumor inoculation. This antitumor activity was paralleled with higher CTL activity and IFN-gamma production by TDLN and spleen cells in the astaxanthin-fed mice. CTL activity by TDLN cells was highest in mice fed astaxanthin for three weeks before inoculation. When the astaxanthin-supplemented diet was started at the same time as tumor inoculation, none of these parameters were altered by dietary astaxanthin, except IFN-gamma production by spleen cells. Total serum astaxanthin concentrations were approximately 1.2 mumol/l when mice were fed astaxanthin (0.02%) for four weeks and appeared to increase in correlation with the length of astaxanthin supplementation. Our results indicate that dietary astaxanthin suppressed Meth-A tumor cell growth and stimulated immunity against Meth-A tumor antigen.

Dietary curcumin with cisplatin administration modulates tumour marker indices in experimental fibrosarcoma.

Curcumin, the active constituent of Curcuma longa, which itself possesses antitumour activity against experimental tumours, enhances the antitumour effect of the widely used anticancer drug cisplatin, when used in combination against fibrosarcoma. Tumour marker enzymes such as aminotransferases, lactate dehydrogenase, gamma-glutamyl transpeptidase, alkaline phosphatase, 5'-nucleotidase were analysed in liver and kidney homogenates of experimental rats. All these enzyme activities were markedly increased in tumour bearing animals. On cisplatin administration, the enzyme levels were decreased but not to near normal values. Curcumin, when treated along with cisplatin brought back the enzyme levels to near the control values. Thus curcumin and cisplatin combination may be worth trying against tumours like fibrosarcoma.

Viscum album L. preparation Isorel modifies the immune response in normal and in tumour-bearing mice.

The Viscum album (mistletoe) preparation Isorel is able to destroy tumour cells and to modify immune reactivity against a particular antigen in normal and in tumour-bearing animals. CBA/HZgr mice and methylcholanthrene-induced fibrosarcoma were used in these studies. A single dose of Isorel M (140 mg/kg or 1400 mg/kg body weight) significantly increased the number of plaque forming cells if applied at the time of injection of sheep red blood cells or 1 day earlier. The application of Isorel 1 day after sheep red blood cells did not modify the number of plaque forming cells in comparison to the controls. The higher the dose of Isorel the stronger is the immune response to sheep red blood cells. Furthermore, one dose of Isorel (140 mg/kg body weight) restored the suppressed immune response of fibrosarcoma-bearing mice to a significant extent. Besides modification of the humoral immune response, the survival time of C57BI/GoZgr male skin grafts on syngeneic female recipients was significantly shorter if Isorel was applied at a particular time after grafting. However, according to plaque forming cell numbers, a prolonged application of Isorel was significantly immunosuppressive in normal mice and particularly in tumour-bearing mice. It should be mentioned that the doses of Isorel used in this experiment were much higher than generally used in cancer patients. In view of the immunomodulating effects of Isorel, the monitoring of the immune response of the patients treated with mistletoe preparations is to be recommended.

Protective effect of magnesium supplementation on experimental 3-methyl cholanthrene-induced fibrosarcoma and changes in tissue magnesium distribution during carcinogenesis in rats.

In this study, we wanted to examine the effect of magnesium (Mg2+) supplementation on the experimental 3-methyl cholanthrene (3-MC)-induced fibrosarcoma and alterations in (Mg2+) distribution in several tissues of the rats, during carcinogenesis. It was determined that serum and tissue (Mg2+) levels of the rats in (Mg2+)-supplemented diet group were higher than those of the rats in the (Mg2+)-nonsupplemented and control groups. The mean time of fibrosarcoma development for (Mg2+)-supplemented group was longer than (Mg2+)-nonsupplemented group (p < 0.05). Symptoms of hypermagnesemia were not observed in any of the rats. These results suggests that dietary (Mg2+) supplementation may have a partial anti-carcinogenic effect on experimental 3-MC-induced fibrosarcoma by prolongation of the latent period of carcinogenesis.

Enhanced biological activity of human recombinant interleukin 2 coupled to mouse red blood cells as evaluated using the mouse Meth A sarcoma model.

In order to circumvent the toxicity associated with high-dose interleukin 2 (IL2) administration and its rapid clearance from the circulation, a carrier system for IL2 is needed. Red blood cells (RBCs) coated with recombinant interleukin 2 (rIL2) provide a means of delivering IL2 into the system in a continuous low-dose manner which, in turn, maintains a low, potentially non-toxic, IL2 concentration. Murine RBCs coated with rIL2 (RBCs-rIL2) are able to induce cytotoxic activity in mouse spleen cells in vitro against malignant murine YAC-1 cells (53-62% cytotoxicity) using less than 4500 i.u./10(9) RBCs per mouse. Cytotoxicity (21-31%) becomes apparent upon cytotoxic testing of spleens cells stimulated in vivo. Using the murine Meth A sarcoma model, the effectiveness of this RBC-rIL2 vehicle is demonstrated in vivo by a 84% reduction in tumour size as compared with the soluble-rIL2-treated mice. Moreover, the RBC-rIL2 vehicle is able to induce tumoricidal cytotoxicity with very low rIL2 concentrations (about 10,000 i.u. of rIL2/mouse). These results indicate that rIL2 retains its biological activity when bound to the RBC and therefore could prove useful as a therapeutic delivery system for cancer treatment.

A mathematical model for the effect of red light penetration depth on tumor growth.

The effect of different local temperature increase in normal and tumorous tissue, influenced by red light commonly used in photodynamic therapy, on tumor growth rate was reanalyzed, taking into account the tumor tissue penetration depth of the light used. The rear part of the tumor is definitely not receiving the same light dose, and consequently the same amount of heat energy, as the front part. The effect is taken into account by using a mathematical model of tumor growth for the rear part of the tumor. Positive experimental results of hyperthermia due to the energy deposited by the red light, are more encouraging after such a correction than previously reported.

Insulin protects against hepatic bioenergetic deterioration induced by cancer cachexia: an in vivo 31P magnetic resonance spectroscopy study.

The bioenergetic effects of cancer cachexia on the livers of male Fischer rats inoculated with a methylcholanthrene-induced sarcoma were assessed using serial in vivo 31P magnetic resonance spectroscopy. Rats were randomized into three groups: tumor-bearing controls (n = 7); an insulin-treated group receiving 2 units/100 g body weight/day starting 21 days after implantation (n = 8); and a chronic insulin-treated group receiving insulin every day after implantation (n = 3). During the 32-day study, serial measurements of food intake, body weight, and tumor volume were taken, and 31P magnetic resonance spectroscopy analyses of the livers were conducted every 7 days after tumor implantation. Neither the short-term nor the chronic insulin treatment regimens stimulated the progress of tumor growth. However, both treatments prevented body weight loss, and the short-term insulin treatment prevented tumor-induced decrease in food intake relative to the control group. Liver bioenergetic deterioration was evaluated from the increase in the ratio of Pi to ATP obtained from the hepatic 31P magnetic resonance spectra. At day 28 postimplantation, control rats exhibited appreciable hepatic bioenergetic deterioration, i.e., a Pi/ATP ratio of 1.41 +/- 0.35 (SE), significantly higher (P < 0.05) than the Pi/ATP ratio for short-term or chronic insulin treatment groups (Pi/ATP 0.92 +/- 0.22 and 0.84 +/- 0.22, respectively) or rats before tumor implantation (Pi/ATP 0.76 +/- 0.14). This insulin-induced bioenergetic protection occurred at any given tumor burden up to at least 10%. Thus, both short-term insulin given just prior to the frank manifestations of cancer cachexia and chronic insulin treatment given throughout tumor growth ameliorated host hepatic bioenergetic deterioration without significantly stimulating tumor growth. Insulin may act by altering the host metabolism (stimulation of liver glucose uptake and utilization, decreased energy-requiring gluconeogenesis, and general protein-sparing action) at the expense of the tumor.

Evaluation of carcinogenicity and chronic toxicity associated with orthopedic implants in mice.

The carcinogenicity and chronic toxicity of 316L stainless steel, nickel, Ti-6A1-4V, hydroxyapatite (HA)-coated Ti-6A1-4V, aluminum oxide containing yttrium oxide, and zirconium oxide containing yttrium oxide were evaluated by implanting solid rods of each material in the thigh muscle of C57BL/6N mice for 24 months. Nickel alloy showed high carcinogenic and toxic potencies, whereas other materials showed no evidence of them. Tumors retaining nickel alloys were malignant fibrous histiocytoma or fibrosarcoma. In some cases, lymphomata that seemed to develop spontaneously were found around the implants because lymphocytes were known to accumulate in chronic inflammatory lesions, and this phenomenon also might be applied to lymphoma.

Antitumorous and immunomodulatory effects of the Viscum album L. preparation Isorel.

There are numerous data on the immunostimulative and antitumorous activity of various Viscum album tissue extracts. Isorel (Novipharm, Austria) is one of these compounds. We found that in mice an increased number of plaque-forming cells to sheep red blood cells (SRBC) followed the injection of Isorel together with SRBC. Further, survival time of a foreign skin graft was shortened if Isorel was applied at the correct time. Finally, suppressed immune reactivity in tumorous mice recovered following Isorel injection. Isorel was further shown to be cytotoxic to tumor cells in vitro. Its application to tumor-bearing mice could prolong their life but without any therapeutic effect. However, a combination of local irradiation and Isorel was very effective: following 43 Gy of local irradiation to a transplanted methylcholanthrene-induced fibrosarcoma (volume about 240 mm3) growing in syngeneic CBA/HZgr mice, the tumor disappeared in about 25% of the animals; the addition of Isorel increased the incidence of cured animals to over 65%. The combined action of Isorel, influencing tumor viability on the one hand and the host's immune reactivity on the other, seems to be favorable for its antitumor action in vivo.