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Stimulation of human and murine bone marrow cell colony formation by colony-stimulating factors obtained from the urine of mice bearing leukocytosis-inducing fibrosarcoma.

Dialyzed urine of mice bearing leukocytosis-inducing fibrosarcoma stimulated granulocyte colony formation in semisolid agar culture of human bone marrow cells. Removal of phagocytic cells prior to stimulation did not interfere with the formation of these colonies in the culture. On the other hand, macrophage colonies were predominantly produced when murine bone marrow cells were stimulated by the dialyzed mouse urine. The activity of colony-stimulating factor (CSF) in the urine of normal mice was less than 1/100 of that in the urine of tumor-bearing mice. DEAE-cellulose column chromatography separated the activity stimulating human granulocyte colony formation from that stimulating murine macrophage colony formation. Further purification showed that a sialoglycoprotein with an apparent molecular weight of 80,000 corresponded to the macrophage CSF, which was devoid of activity toward human cells. The molecular properties of the human-active granulocyte CSF could not be studied further, because it was quite unstable.

Animals↗

The efficiency of DNA strand-break repair in two fibrosarcoma tumors and in normal tissues of mice irradiated in vivo with X rays.

We have used alkaline elution to study the repair of X-ray-induced DNA strand breaks in vivo in two fibrosarcoma tumors and in several normal mouse tissues after whole-body irradiation of mice with 10-12.5 Gy of X rays. Both tumors were found to repair damage significantly faster and to a greater extent than any of the normal tissues, so that by 2 hr after irradiation the level of damage in both tumors was indistinguishable from unirradiated control values. Of the normal tissues studied, liver repaired the fastest. The kinetics for the other normal tissues were essentially the same, showing an appreciable level (7-16%) of unrepaired lesions still evident after 2 hr. Even as late as 12 hr there was a significant amount of residual damage in some tissues, with testes and spleen showing the greatest level (ca. 15%). The repair kinetics for each tissue were not appropriately described by a sum of two exponentials. In contrast, previously reported data for many homogeneous mammalian cell systems in vitro and for some tissues in vivo have shown biphasic repair kinetics. This difference may be related to heterogeneity of both cell type and environment within the tissue populations used in the investigation. The faster repair of DNA strand breaks by tumor cells relative to cells from normal tissues was not readily explainable in terms of such radiobiological parameters as overall tissue oxygenation or sulfhydryl content. Rather, it appears that the degree of differentiation of the cells within the tissue population may be a major determinant of repair proficiency. Based on a model incorporating a competition between repair and fixation of sublethal lesions, these data are consistent with the idea that tumor cells may have a repair, and hence survival, advantage over normal cells in response to ionizing radiation.

Animals↗

A mutant HSDM1C1 fibrosarcoma line selected for defective eicosanoid precursor uptake lacks arachidonate-specific acyl-CoA synthetase.

Mutagenesis followed by suicide with highly radioactive tritiated arachidonic acid has been used to select for mouse fibrosarcoma (HSDM1C1) cells defective in eicosanoid precursor uptake. Survivors of the selection were screened by replica plating and autoradiographic assay of [3H]arachidonate esterification; a mutant cell line, EPU-1, was established. EPU-1 cells contain one-third as much arachidonate as normal HSDM1C1 cells. The mutant lacks arachidonate-specific acyl-CoA synthetase, which accounts for decreased arachidonate uptake. EPU-1 exhibits enhanced turnover of arachidonoyl- but not linoleoyl-phosphatidylcholine. Bradykinin-induced arachidonate release and prostaglandin E2 synthesis are decreased in EPU-1. Thus, arachidonoyl-CoA synthetase is required for arachidonate homeostasis in HSDM1C1 cells.

Animals↗

Characterization of immunosuppressor cells in rats immunized with solubilized tumor-associated antigens prepared from a methylcholanthrene-induced fibrosarcoma.

Antiimmune responses in rats previously immunized with soluble tumor antigens prepared by sodium deoxycholate (DOC-STA) from chemically induced fibrosarcoma KMT-17 were measured by the Winn assay. Enhancement of tumor growth was demonstrated at a tumor:effector ratio of 1:500 with DOC-STA-immune spleen cells, although inhibition of tumor growth was demonstrated at a tumor:effector ratio of 1:100. The tumor-neutralizing ability of KMT-17-immune spleen cells was abrogated when DOC-STA-immune spleen cells were added to a mixture of KMT-17 cells and KMT-17-immune spleen cells. This suppressor activity of the spleen cells was diminished by the treatment with rabbit anti-rat T-cell serum and immune complement. The suppressor activity of DOC-STA-immune spleen cells was also shown in 51Cr release assay and was specific for the tumor line used. After fractionation of spleen cells from DOC-STA-immune rats by the Ficoll density gradient, the cells in the light layer showed an enhancing effect on tumor growth detected by the Winn assay, whereas the cells in the heavier region of the gradient had an inhibiting effect.

Animals↗

[Sellar fibrosarcoma following radiotherapy for prolactinoma].

A 51-year-old house woman visited the Department of Neurosurgery, Osaka University Hospital for examination of the head injury on Oct. 7, 1975. Neurological examination was normal. Endocrinological examination showed galactorrhea. The patient had a past history of premature menopause. Plain skull films revealed enlargement of sella turcica and CT scan showed sellar tumor with suprasellar expansion which was enhanced by contrast medium. The serum prolactin (PRL) level was 3,290 ng/ml. Diagnosis of PRL secreting pituitary adenoma (prolactinoma) was made. Though surgical removal of the tumor was recommended, it was refused by the patient. Therefore, careful observation was continued as an out-patient until May 1979 when she noticed a temporal hemianopsia of her left eye. She was admitted and had partial removal of the tumor via frontal route and subsequent irradiation (total dose of 5,000 rad by Lineac). The tumor was verified to be a prolactinoma by the immunohistochemical staining. Postoperative course was uneventful and she lead a normal life. In Oct. 1981, severe faceache began and she was readmitted. Sella was destructed extensively and CT scan revealed a hugh sellar tumor with multi-directional extrasellar extension which was less enhanced than that of the first study. The serum PRL level was 588 ng/ml and the regrowth of prolactinoma was suspected. High dose bromocriptine (40 mg/day) therapy was started. The serum PRL level rapidly fell to the negligible value, however, shrinkage of the tumor was not observed. On Jan. 20, 1982, suddenly she developed a left hemiparesis and her level of consciousness gradually deteriorated. On Mar. 11, 1982, the second operation was performed and a solid firm tumor in the base of the skull was partially removed. The tumor was histologically verified to be a fibrosarcoma. After the second operation bromocriptine therapy was discontinued, however expected elevation of the serum PRL level was not recognized. She died on Apr. 4, 1982.

Adult↗

Influence of two prostaglandin synthesis inhibitors on the intratumor distribution of blood flow and vascular volume in a transplantable rat fibrosarcoma.

The intratumor and intramuscle distribution of blood flow and plasma volume was studied via isotope techniques in a transplantable rat fibrosarcoma. Administration of two prostaglandin synthesis inhibitors, indomethacin and diclofenac-sodium, had different effects. Indomethacin changed muscle plasma volume significantly towards higher values; a tendency to increased tumor plasma volume was also found. Diclofenac-sodium increased tumor blood flow, but had no significant influence on other parameters. These effects are discussed based on previous observations of reduction of tumor growth rate and tumor vascularization after administration of both drugs.

Animals↗

Effect of selenium in combination with cis-diamminedichloroplatinum(II) in the treatment of murine fibrosarcoma.

cis-Diamminedichloroplatinum(II) (cis-DDP) is a well-known anticancer agent the use of which is limited by its toxicity. Since it has been demonstrated that selenium is able to combine with metals like cadmium and mercury and to reduce their toxicity, we decided to investigate whether it could reduce the toxicity of platinum. We treated fibrosarcoma-bearing mice with a combination of cis-DDP and selenium. The dose of 2 or 4 micrograms selenium/g animal weight had no effect on tumor growth. The i.p. injection of 16 micrograms cis-DDP/g led to early death of animals. The i.p. treatment of tumor-bearing animals with 2 or 4 micrograms of selenium reduced the early mortality induced by cis-DDP at a dose of 16 micrograms/g. Therefore, the addition of selenium allowed the administration of high doses of cis-DDP, which resulted in an improved antitumor effect. Clonogenic assays following drug exposure showed that selenium had no direct effect on tumor cells and did not modify the antitumor activity of cis-DDP. Electron microscopy showed reduced changes in renal cells when selenium was added to the cis-DDP treatment. Microanalysis showed no accumulation of either selenium or platinum within renal cells. These results suggest that the addition of selenium decreases the nephrotoxicity of cis-DDP.

Animals↗

[Fibrosarcoma of the right ventricle of the heart--a contribution to the pathology of the primary sarcoma of heart and pulmonary arteries (author's transl)].

The clinical signs as well as the pathological-anatomical and histological peculiarities of a case of fibrosarcoma of the right ventricle of the heart in a fifty-years-old women are described. Examining of all cases described in literature it becomes evident that when ascertaining the starting points, there is a fluent transition from the sarcoma of the endocardium to the sarcoma of the pulmonary arteries. Four types become evident. The morphological pecularities of the appearance of Anitschkow-cells are described. Origin and importance of these cells are not known yet in all their details. The Survey over the single observations speaks in favour of their affiliation to the cellular defence system of the heart.

Female↗

Heparin effect on DNA synthesis in a murine fibrosarcoma cell line: influence of anionic density.

The effects of heparin subfractions on DNA synthesis in a murine cutaneous fibrosarcoma cell line were examined. Porcine mucosal heparin was preparatively fractionated for anionic charge density by DEAE-Sephadex chromatography and for molecular weight by Sephadex G-100 filtration. The cell line was plated from confluent monolayer cultures and grown in medium and fetal bovine serum, with or without a heparin fraction at a final concentration of 10 micrograms/ml. At intervals thereafter, the cells were pulsed with [3H]thymidine. A low-charge density heparin fraction stimulated [3H]thymidine incorporation (cpm/mg protein and cpm/cell) during the first 3 days of growth compared to control values without added heparin, whereas a high-charge density heparin fraction had little of this effect (186 +/- 35% of control vs. 101 +/- 14%, respectively; P less than .05). The augmentation of DNA synthesis observed with the low-charge density fraction correlated with increased proportions of cells in S and G2 phases compared with those of the controls, as determined by flow cytofluorometry. Low- and high-molecular-weight heparin fractions did not significantly alter DNA synthesis. Heparin subfractions are thus heterogeneous with respect to their effect on cellular DNA synthesis in this tumor line.

Animals↗

Macrophage colony-stimulating factor and granulocyte colony-stimulating factor separated from fibrosarcoma tissue in mice.

Large increases of granulocytes and monocytes were found in the blood of mice bearing fibrosarcoma. Extraction of the tumor tissue with isotonic saline yielded a colony-stimulating factor (CSF). Further extraction of the saline-insoluble materials with 0.1% sodium dodecyl sulfate afforded another pool of CSF. Incubation of the tumor cells in vitro resulted in the accumulation of CSF activity in the culture medium. The CSF from these sources produced both granulocyte colonies and macrophage colonies in murine bone marrow cell culture. Subsequently, the activity producing granulocyte colonies was separated from that producing macrophage colonies by isoelectrofocusing and repeated gel-filtration chromatography. It was also shown that anti-L cell CSF antiserum neutralized the macrophage CSF activity but not the granulocyte CSF activity. These results show that the granulocytosis-inducing tumor produces two types of CSF.

Animals↗

Glycosphingolipids in clonal variants of rat fibrosarcoma cells with different transplantability.

Neutral glycolipids and gangliosides of four clonal variants of rat fibrosarcoma AS-653 cells with different transplantability were analyzed. A highly malignant clone A had a much lower quantity of GM3 ganglioside and a much higher quantity of lactosylceramide as compared to clones Z and G, which showed low transplantability and less malignancy, and a variant clone P, which showed tumorigenicity only in ascites form. A similar correlation was found with the quantity of an unidentified slow-migrating neutral glycolipid in various clones. This glycolipid was present in trace amount in the original highly malignant clone A, increased moderately in clones G and Z, and increased greatly in clone P, which showed no subcutaneous transplantability. The results of these studies suggest that a blockage of synthesis of GM3 ganglioside and a long chain neutral glycolipid occurred with enhanced malignancy, and an enhanced synthesis of GM3 ganglioside and the long chain neutral glycolipid is associated with a decrease in transplantability.

Animals↗

Simple method for quantifying pulmonary metastases in a murine fibrosarcoma.

A simple method is described for quantitating pulmonary metastases in C57BL/6J mice implanted with the Lewis T241 fibrosarcoma. Lungs were removed from tumor-bearing mice, homogenized, and diluted to 14 ml with supplemented Roswell Park Memorial Institute Tissue Culture Medium 1640 (+5% fetal calf serum). Twenty-five microliters of lung suspension from individual mice were added to a flat-bottomed microtiter plate containing 175 microliters of supplemented media, pulsed with [3H]thymidine, and incubated for 20 hr at 37 degrees. The cells were processed with a multiple automated sample harvester and counted in a liquid scintillator. Total lung burden was extrapolated from measured radioactivity (as cpm) through the use of a standard curve. This method is reasonably accurate and precise and provides more quantitative information on the pulmonary metastatic process than most conventional assays.

Animals↗

[Fibrosarcoma as a cause of cardiac tamponade].

Primary malignant tumours of the heart are exceptionally rare, what makes them particularly interesting for their research; on the other hand, clinical diagnosing of these tumours is even rarer. The authors present a patient with fibrosarcoma of the heart, which provoked the acute pericardial tamponade. The patient was successfully operated upon. The diagnosis was confirmed during the surgery itself with temporary biopsy. After the surgery the authors administered chemotherapy according to the VAC scheme (vincristine++, actinomycin D and cyclophosphamide ).

Cardiac Tamponade↗

Enhancement of the DNA cross-linking activity of nitrogen mustard by misonidazole and diethyl maleate in a mouse fibrosarcoma tumor in vivo.

We have used the technique of alkaline elution to determine the amount of nitrogen mustard (HN2)-induced DNA cross-linking in a murine fibrosarcoma tumor in vivo. Mice were either treated with HN2 directly or were pretreated with misonidazole (MISO) or diethyl maleate prior to injection with HN2. Two types of HN2-induced DNA lesions were detected, namely, proteinase K-sensitive and -resistant cross-links. Pretreatment with MISO did not appear to affect the ratio of the two types of lesion. In mice treated with HN2 alone, the amount of cross-linking reached a high level by 0.5 hr postinjection, after which these lesions were repaired, 62% of cross-links being removed between 0.5 hr and 6 hr postinjection. Pretreatment of mice with MISO resulted in substantial alterations in both the magnitude and time course of cross-linking during the first few hr after injection of HN2. Both MISO and diethyl maleate enhanced the number of cross-links formed at 0.5 hr postinjection. Furthermore, in MISO-pretreated mice, only 18% of the cross-links present at 0.5 hr had been removed by 6 hr postinjection. This early enhancement is possibly related to glutathione depletion resulting in reduced intracellular inactivation of HN2. Since repair processes were determined not to be saturated at the level of lesions under study, these data suggest that, in addition to the initial glutathione depletion resulting in an increased burden of damage, MISO may also inhibit DNA repair processes, possibly via a hypoxia-dependent interaction between MISO reduction products and DNA or repair enzymes. Assuming that DNA cross-linking is related to the cytotoxicity of HN2, these effects may account for the MISO enhancement of HN2 toxicity toward various biological systems which have been reported previously. It appears that chemosensitization may result from a variety of factors, with the relative importance of each factor depending on the particular drug being used.

Animals↗

Independent effect of a mixed-beam regimen of fast neutrons and gamma rays on a murine fibrosarcoma.

Biological effectiveness of a mixed-beam regimen of fast neutrons and photons was studied in an animal tumor system. NFSa , a spontaneous fibrosarcoma in a C3H mouse, was transplanted in the right hind legs of syngeneic male mice and locally irradiated with a single dose or five daily doses. Tumor control experiments showed that five gamma-ray doses increased TCD50 values by 20 Gy and produced a shallower slope on the dose-response curve compared to that after a single fraction. Fractionated neutron doses also increased the TCD50 value by 9 Gy without changing the slope of the dose-response curve. A mixed-beam regimen of N-gamma-gamma-gamma-N resulted in an independent effect on the tumor. Second, tumor cell survival was examined by the lung colony assay. Nembutal anesthesia reduced the tumor oxic cell fraction, resulting in a single component dose-response curve after a single gamma ray. Five fractionated doses of gamma rays increased both D0 and extrapolation number while those of fast neutrons increased only extrapolation number. The D0 and extrapolation number of the mixed-beam regimen were again identical to those values assuming that the mixed-beam effect was independent. RBEs obtained from cell survival were fairly close to those from TCD50 assays except single-dose experiments.

Animals↗

Fibrosarcoma affecting the mammary gland of a cow.

A highly malignant fibrosarcoma which arose in or close to the mammary gland of a 12 year old Ayrshire cow, with metastases in local lymph nodes, lungs, liver, kidney and adrenal glands has been described. The tumors were densely cellular and consisted of interweaving bands of fusiform cells with a high mitotic index. Infiltration of normal tissues and invasion of blood vessels were characteristic features. Ultrastructural study of the cells revealed mesenchymal cells with abundance of rough endoplasmic reticulum and cytoplasmic vesicles and they were closely invested with collagen fibers.

Animals↗