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Humoral factors of ascites sarcoma 180 stimulate osteoblastic UMR 106-01 cell proliferation and bone resorption via signal transduction pathways, which are clearly different from those of parathyroid hormone.

Ascites sarcoma 180 (S180A) is a transplantable tumor that induces hypercalcemia in tumor-bearing mice and stimulates bone resorption in cultured neonatal mouse calvaria without parathyroid hormone (PTH)-like activity. The serum-free conditioned media of S180A cell cultures (S180A-CM) stimulated [3H]thymidine incorporation (178.3% of the control) and inhibited alkaline phosphatase activity (39.0% of the control) in the osteoblastic osteosarcoma cell line UMR 106-01, contrary to PTH. To investigate signal transduction by S180A-CM, we determined the levels of intracellular free calcium ([Ca2+]i), inositol 1,4,5-triphosphate (IP3), 1,2-diacylglycerol (DAG), phosphatidylcholine (PC) and protein kinase (PK) C activity in UMR 106-01 cells. PTH and PTH-related protein (PTHrP), both potent bone-resorbing factors (BRFs), caused an increase in [Ca2+]i and stimulated IP3 production, whereas S180A-CM had little or no effect on these parameters. On the other hand, S180A-CM stimulated DAG production, accompanied by PC breakdown, and the translocation of PKC activity from the cytosol to the membrane fraction. Sphingosine, a specific PKC inhibitor, inhibited bone-resorbing activity (BRA) in S180A-CM more effectively than PTH or PTHrP-stimulated resorption. H-7, an inhibitor of both cAMP-dependent PKA and PKC, completely inhibited BRA in S180A-CM. These results suggest that BRFs of S180A-CM stimulate osteoblastic cell proliferation and bone resorption via two signal transduction pathways, which are different from those of PTH: 1) activation of PKC by DAG resulting from PC hydrolysis and 2) activation of PKA subsequent to prostaglandin E2 production by bone.

Animals↗

[Evolution of weight and survival of C3H mice with solid, subcutaneous sarcoma 180, treated with radiotherapy, hyperthermia and a combination of hyperthermia and radiotherapy].

The authors make an experimental study of the weight evolution and survival rate of sarcoma 180-bearing C3H mice treated by combinations of radiotherapy and hyperthermia. The body weight increased progressively in control animals. The weight increase was less marked under the effect of radiotherapy, hyperthermia, and radiotherapy plus hyperthermia, in decreasing order. While tumor-bearing control animals died after an average of 26.6 days, 3.33, 16.67 and 76.67 per cent of the mice treated respectively by radiotherapy, hyperthermia, and radiotherapy plus hyperthermia were living after 90 days.

Animals↗

Experimental chemotherapy with 5-arylpyrimidine antifolates: preliminary studies on toxicity and responsiveness of sarcoma 180 to DDMP (NSC-19494) and DDMP with citrovorum factor (NSC-3590).

The 5-arylpyrimidine antifolate DDMP showed appreciable therapeutic activity against an ascitic form of Sarcoma 180 in BD2F1 mice. Antitumor effects were highly schedule and dose dependent at a limited number of doses within the range of 8--40 mg/kg. The best results (increased lifespan = 112%) were obtained with two doses of DDMP at 40 mg/kg given 4 days apart. The incorporation of citrovorum factor rescue in dose schedules with DDMP appeared to improve the therapeutic index. In multiple-dose schedules with citrovorum factor allowing an average of eight doses of DDMP at a maximum level of 16 mg/kg, increases in median lifespan were greater than 158% with a number of long-term survivors.

Animals↗

Action of demecolcine (colcemid) in the murine sarcoma 180 tumor.

Iv infusions of demecolcine (Colcemid) were established in mice bearing the Sarcoma 180 tumor. During demecolcine infusion at a rate of 6 microgram/hr, the tumor labeling index following 3H-thymidine administration and the mean grain count per labeled cell did not differ significantly from control values. Cells in anaphase and telophase disappeared from the tumor sections, and the net number of cells in the earlier stages of mitosis increased for 20 hrs. The rate of mitotic accumulation during the initial 8 hrs of demecolcine infusion was about one third of what would be expected from the known cell cycle values for this tumor. This reduced rate of accumulation does not appear to result from death of mitotic cells, escape of cells from metaphase blockade, or S-phase arrest secondary to inhibition of DNA synthesis; it is suggested that the reduced accumulation rate is secondary to demecolcine damage to interphase cells. Tumor cells that have been gathered by 4-hr demecolcine infusions may be released in synchronous fashion following the end of the infusion. A small proportion of these cells will recycle synchronously during the following mitotic period.

Anaphase↗

[The effect of a synthetic fragment of human interleukin-2 on the growth and vascularization of sarcoma 180 in mice].

The effect of a modified peptide of the middle part of the human interleukin-2 molecule (C-1-6) on the growth of transplantable sarcoma 180 of mice was studied. C-1-6 injected intraperitoneally in the dose of 0.5, 5 and 50 micrograms 4 times every other day was shown to stimulate tumor growth and enhance angiogenesis induced by the tumor transplanted intracutaneously. Stimulation of tumor growth was most apparent when the agent was given late (on day 4) after transplantation. Supernatants of murine peritoneal macrophages activated by 1 microgram/ml solution of C-1-6 proved capable of stimulating tumor growth, too. It is suggested that the stimulating effect of C-1-6 on tissue regeneration be investigated.

Animals↗

Depression of resistance against Salmonella infection in sarcoma 180-bearing mice and its restoration by Salmonella mini-cells.

The reduction of resistance against Salmonella infection was resulted from the reduction of macrophage activities in Sarcoma 180-bearing mice. Mean survival day of S180-bearing mice was markedly reduced to 1.4 +/- 0.5 days after the challenge with 1 X 10(8) of Salmonella typhimurium LT2 cells in contrast with 6.8 +/- 1.9 days of normal mice. Eighty percent of S180-bearing mice died within 14 days after the challenge with 1 X 10(6) of LT2 cells, whereas all of normal mice survived more than 30 days after the challenge with 3 X 10(6) or less of LT2 cells. Chemotactic and O2- producing activities of macrophages collected from S180-bearing mice which were treated with Salmonella mini-cells restored to normal level. Bactericidal activity of macrophages was also restored by the mini-cell treatment. The restoration of the resistance to Salmonella was accompanied with increases of macrophage activities.

Animals↗

Histopathological and immunophenotyping studies on normal and sarcoma 180-bearing mice treated with a complex homeopathic medication.

Canova is a homeopathic complex medicine, used as an immune modulator. We studied its effects in normal and sarcoma 180-bearing mice. Three control groups were also evaluated. The mice were examined at daily intervals and the tumours observed histologically. Peripheral blood was analysed by flow cytometry. A delay in the development, and a reduction in size of the tumours, and increased infiltration by lymphoid cells, granulation tissue, and fibrosis surrounding the tumour were observed with active treatment compared to control. All animals from the treated group survived, 30% of control groups died. In 30% of treated animals, a total regression of the tumour was confirmed using light microscopy, no regression was found in the control groups. Treatment with Canova increased total numbers of leukocytes and lymphocytes. Among lymphocytes, TCD4, increased in normal-treated group and B and NK cells in S180-treated groups. The results reflect enhanced immune response of the host after treatment with Canova.

Animals↗

Ascites sarcoma 180, an animal model of humoral hypercalcemia of malignancy, produces a factor(s) exhibiting potent bone-resorbing activity without any parathyroid hormone-like activity.

Ascites sarcoma 180 (S180A) is a transplantable tumor maintained in ddY mice. In the tumor-bearing mice, the plasma Ca, Pi and acid phosphatase levels increased and the plasma alkaline phosphatase levels decreased. The elevation of plasma Pi levels is unusual in humoral hypercalcemia of malignancy (HHM). To characterize the pathogenesis of HHM in the animals, the biological activities in the serum-free conditioned media (CM) of S180A cell cultures were examined. The S180A CM stimulated bone resorption dose dependently and showed TGF-like, IL-1-like and mitogenic activity. Unlike parathyroid hormone (PTH), the factor(s) failed to stimulate cAMP production by either UMR 106-01 cells or neonatal mouse calvaria at concentrations that stimulate bone resorption. Also, the factor(s) stimulated proliferation of UMR 106-01 cells concomitant with a slight increase in intracellular calcium levels. These results indicate that S180A cells produce a factor(s) responsible for bone resorption which is apparently different from PTH-like activity.

Acid Phosphatase↗

[Effects of Xuanyinning Recipe on invasion of SPC-A-1 cells and pathomorphological changes of peritoneum in mice inoculated with sarcoma 180].

OBJECTIVE: To observe the effects of Xuanyinning Recipe (XYNR) in inhibiting SPC-A-1 cellular infiltration and on the pathomorphological changes of peritoneum in mice inoculated with sarcoma 180 (S(180)). METHODS: On the bases of isolated culture of mouse peritoneal mesothelial cells, we adjusted and added the human lung adenocarcinoma cell line SPC-A-1 into the double-layer culture medium to observe the number of clones formed. We also took out the peritoneum from the mice administered with three different dosages of XYNR and observed its pathomorphological changes with transmission electron microscope. RESULTS: In the in vitro experiment, the number of clones of SPC-A-1 in culture medium with XYNR (50 microg/ml) decreased distinctly. In the in vivo experiment, it was observed that, in the peritoneum from the XYNR-treated mice inoculated with S(180), the mesothelial cells arranged more and more regularly with the increasing of the dosage of XYNR, while the mesothelial cells in the peritoneum of the mice in the control group necrosed and arranged loosely. CONCLUSION: XYNR can inhibit the invasion of SPC-A-1 cells. It also can improve the loose arrangement of the peritoneal mesothelial cells in mice inoculated with S(180), so as to inhibit the malignant effusion.

Adenocarcinoma↗

Effects of sarcoma 180 growth on interleukin-1 and circulating immune complexes.

Cultured splenic mononuclear adherent cells (SMAc) from normal BALB/c mice as well as those from mice bearing 10-day sarcoma 180 (S180), exhibited a marked increase in Escherichia coli lipopolysaccharide-stimulated interleukin-1 (IL-1) production, when compared to spontaneous values. On days 20 and 30 following S180 challenge, a decrease in this effect on IL-1 production in treated and untreated SMAc was observed. Concomitantly with the alterations in the regulation of IL-1 production during tumor growth, an increase in the levels of prostaglandin E2 and serum immune complexes could be detected. These data suggest that the immunosuppression associated with later stages of tumor development may be due to direct effects on monocytes, by means of a down-regulation of IL-1 production.

Animals↗

[Experimental study of the effect of the association of hyperthermia and BCNU on solid sarcoma 180 in C3H mice. Development of tumor volume, survival and rate of cure].

The authors describe the experimental results of administering BCNU combined with hyperthermia upon the growth of sarcoma 180 of the mouse. Best results were obtained employing the combined therapy than using BCNU or hyperthermia alone, and hyperthermia was necessary in all cases where a curative effect was attained.

Animals↗

The inhibition by a series of potentially bioreductive naphthoquinones of rat liver mitochondria and sarcoma 180 tumor cell respiration.

A series of potentially bioreductive naphthoquinones were investigated for their effects on rat liver mitochondrial electron transport and energy transfer and their ability to inhibit Sarcoma 180 tumor cell respiration in vitro. It was found that all the naphthoquinones evaluated, inhibited tumor cell respiration and rat liver mitochondrial oxidative metabolism. It was also found that 1,4-naphthoquinones substituted at the 2 and 3 positions were more effective inhibitors of the respiratory and energy transfer systems studied than those substituted at the 2 position only. 2,3-bis(chloromethyl) 1,4-naphthoquinone was found to cause the most rapid onset of inhibition, cause an immediate burst of cyanide insensitive respiration, and cause a preferential reduction of cytochromes c, a and a3 following oxygen depletion.

Animals↗