Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “FIBROSARCOMA”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 775 records · Page 43Linked to original sources
PubMed1981

The influence of intraperitoneal injections of histamine on tumour growth in fibrosarcoma-bearing mice.

Twenty C57BL/6 male and 20 C3H female mice carrying a methyl cholanthrene-induced fibrosarcoma received, daily, intraperitoneal injections of histamine dihydrochloride (1.8 mg or 6 mg histamine base/mouse). In all histamine-treated C57BL/6 mice, tumour growth was significantly slower than in control mice until day 18. Thereafter, the tumour growth rate of treated compared to control mice was accelerated. In 10 out of 20 C3H mice, tumour growth was significantly slower until day 25; in histamine responsive C3H mice, histological studies showed numerous and large loci of acute haemorrhagic necrosis in the tumours.

Animals↗
PubMed1984

Induction of murine fibrosarcomas by low dose treatment with 3-methylcholanthrene followed by promotion with 12-O-tetradecanoyl-phorbol-13-acetate.

Repeated application of the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA) to the skin of mice previously treated with an initiating dose of the carcinogen 7,12-dimethylbenz[a] anthracene has been shown to lead to an increased incidence of papilloma. The studies presented here describe a modified murine two-stage carcinogenesis model in which a single subcutaneous administration of the carcinogen 3-methylcholanthrene (3-MC) is followed by multiple applications of TPA administered subcutaneously or intraperitoneally. TPA was observed to act as a promoter under these conditions when given either subcutaneously or intraperitoneally. When a carcinogenic dose of 3-MC was administered (0.5 mg/mouse) followed by regular treatment with TPA (10 micrograms/mouse) the percent of tumor-bearing mice increased and the length of time until tumors developed significantly shortened. At a subcarcinogenic dose of 3-MC (0.025 mg/mouse), repeated treatment with TPA led to tumor development whereas no tumors were observed in mice not treated with TPA. All tumors were found to be fibrosarcomas. Thus, TPA is capable of acting as a systemic promoter of mesenchymally derived tumors.

Animals↗
PubMed1989

Studies on indomethacin as a potentiator for hyperthermic and radiation responses in a mouse fibrosarcoma.

Indomethacin, a non-steroidal anti-inflammatory drug which is also a calcium antagonist and an inhibitor of prostaglandin synthesis was observed to have a chemotherapeutic effect in a mouse fibrosarcoma. More significantly, administration of the drug before exposure to either radiation or hyperthermia, enhanced their effects. Apart from tumor growth delay, tumor cures were also observed in all the three modalities tested. The data suggests a potential anti-cancer role for indomethacin in combination modalities.

Animals↗
PubMed1991

Distinct patterns of phorbol ester-induced downregulation of protein kinase C activity in adriamycin-selected multidrug resistant and parental murine fibrosarcoma cells.

Specific activators of protein kinase C (PKC), including the phorbol-ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), can reduce the chemosensitivities of a variety of mammalian tumor cell lines and their cytotoxic drug-selected multidrug resistant (MDR) variants to MDR-linked drugs, thus implicating PKC in the MDR phenotype. Previously, we reported that the adriamycin-selected MDR murine fibrosarcoma cell line UV-2237M-ADRR has approximately twice as much PKC activity as the parental UV-2237M line. In this report, we show that the level of [3H]phorbol-12,13-dibutyrate specific binding activity was elevated 3.5-fold in the MDR cells, thus establishing that phorbol-ester responsive PKC is overexpressed in the MDR line. Phorbol esters mediate downregulation of PKC by stimulating proteolysis of the enzyme, without altering the rate of PKC synthesis. We report that the kinetics of TPA-induced downregulation of PKC activity differ markedly in parental and MDR UV-2237M cells, providing evidence that the overexpression of phorbol-ester responsive PKC in adriamycin-selected MDR UV-2237M-ADRR cells results, at least in part, from a reduced rate of PKC degradation in the cells.

Animals↗
PubMed1991

Effect of oxygenation, pH and hyperthermia on RSU-1069 in vitro and in vivo with radiation in the FSaIIC murine fibrosarcoma.

We have evaluated the combination of the radiosensitizing and bioreductive alkylating agent RSU-1069 with hyperthermia and radiation in an attempt to improve the potential effectiveness of hyperthermia and radiation against locally advanced malignancies. In vitro studies in FSaIIC murine fibrosarcoma cells demonstrated that 1 h exposure to RSU-1069 was more cytotoxic toward hypoxic than normally oxygenated cells at 37 degrees C and pH 7.40 and was only minimally more cytotoxic at hyperthermic temperatures. At pH 6.45, however, RSU-1069 became significantly more toxic toward hypoxic cells and its cytotoxicity was markedly increased at hyperthermic temperatures. In contrast, the ability of this agent to radiosensitize hypoxic FSaIIC cells significantly diminished at pH 6.45. Hoechst 33342 diffusion selected FSaIIC tumor subpopulation studies revealed that hyperthermia and RSU-1069 were more toxic towards dim (hypoxic) cells, while radiation was more toxic towards bright (normally oxygenated) cells. A combination of all three modalities resulted in an equal and significant kill of hypoxic and oxygenated cells. These results suggest that the combination of RSU-1069, local hyperthermia and radiation has considerable clinical potential.

Animals↗
PubMed1989

Immunohistochemical localizations of albumin and transferrin accumulated in Rhodamine fibrosarcoma tissue of rats for supporting growth of the tumor cells.

Our recent studies indicated that Rhodamine fibrosarcoma (RdF) tissue of rats accumulated large amounts of albumin and transferrin and that these proteins were essential for growth of RdF cells in primary cultures in serum-free medium. Therefore, the localizations of albumin and transferrin accumulated in RdF tissue were examined by immunohistochemical stainings. Both anti-rat albumin IgG and anti-rat transferrin IgG stained the cell surface of the tumor cells strongly, but the intracellular area only weakly.

Albumins↗
PubMed1991

Expression of laminin by human fibroblasts, HT1080 fibrosarcoma cells and MCF-7 breast adenocarcinoma cells. Lack of regulation by the cell density and extracellular matrix.

We have cultured normal fibroblasts, fibrosarcoma HT1080 cells and breast adenocarcinoma MCF-7 cells on various substrates (plastic, collagen type I, laminin). All cell types used adhered on the three substrates with, however, a delayed attachment on laminin. On all substrates, cell grew as monolayer with the exception of MCF-7 cells that formed clusters on laminin. The epithelial MCF-7 cells as well as mesenchymal cells (fibroblasts and tumoral HT1080 cells) synthesized laminin and expressed mRNA coding for laminin B1 chain and for the 67 kD laminin binding protein. The levels of these mRNAs were not modulated by culture conditions which affect cell morphology nor by cell density.

Adenocarcinoma↗
PubMed1983

Response of fibrosarcoma cell subpopulations to small doses of radiation delivered in situ.

The survival of cells from 2 tumor subpopulations after gamma-ray doses ranging from 1 to 19 Gy was determined using a lung colony assay. Methylcholanthrene-induced fibrosarcomas grown in the hind legs of C3H/Kam pathogen-free mice were irradiated in situ when the tumors were 8-10 mm in diameter. Single cell suspensions prepared from excised tumors were separated on a linear density gradient, and the clonogenicity of predominantly oxic Band 2 (density 1.08 g/cm3) and predominantly hypoxic Band 4 (density 1.14 gm/cm3) cells was measured. The surviving fraction of cells after doses of 1, 2, and 3 Gy was estimated from that measured after total doses of 5 Gy = 5 X 1 Gy, 10 Gy = 5 X 2 Gy, and 15 Gy = 5 X 3 Gy, under the assumption of equal effect per fraction (checked by estimating survival at 3 Gy after different numbers of fractions). Very little curvature was evident in the survival curves of Band 2 and Band 4 cells (beta/alpha = .013-.034 Gy-1). The initial segment of the survival curve of the predominantly oxic Band 2 cells was steeper (1Do = 3.6 Gy) than that of the predominantly hypoxic Band 4 cells (1Do = 5.2 Gy); both remained linear over a large range, to doses in excess of 3 Gy. These results imply that these tumor subpopulations will be insensitive, in their response to multifractionated regimens, to changes in size of dose per fraction in the range 0 to 3 Gy, a trait shared by two acutely responding normal tissues (murine testis and jejunum).

Animals↗
PubMed1986

Tumor size dependent changes in a murine fibrosarcoma: use of in vivo 31P NMR for non-invasive evaluation of tumor metabolic status.

Tumor tissue contains viable hypoxic regions that are radioresistant and often chemoresistant and may therefore be responsible for some treatment failures. A subject of general interest has been the development of non-invasive means of monitoring tissue oxygen. Pulse Fourier transform 31P NMR spectroscopy can be used to estimate intracellular nucleotide triphosphates (NTP), phosphocreatinine (PCr), inorganic phosphate (Pi) and pH. We have obtained 31P NMR spectra as an indirect estimate of tissue oxygen and metabolic status in a C3H mouse fibrosarcoma FSaII. Sequential spectra were studied during tumor growth in a cohort of animals and peak area ratios for several metabolites were computed digitally by computer. During growth, tumors showed a progressive loss of PCr with increasing Pi, and most tumors greater than 250 mm3 in volume had little or no measurable PCr. The smallest tumors (38 mm3 average volume) had PCr/Pi ratios of 1.03 +/- .24, whereas tumors 250 mm3 or more had an average PCr/Pi ratio of 0.15 +/- .04. Similarly derived NTP/Pi ratios decreased with tumor size, but this change was not significant (p = .17). Radiobiologic hypoxic cell fractions were estimated using the radiation dose required to control tumor in 50% of animals (TCD50) or by the lung colony technique. Tumors less than 100 mm3 had a hypoxic cell fraction of 4% (TCD50) while tumors 250 mm3 had a 40% hypoxic cell fraction (lung colony assay). These hypoxic fraction determinations correlated well with the depletion of PCr and decline in NTP/Pi ratios seen at 250 mm3 tumor volumes. Tumor spectral changes with acute ischemia were studied after ligation of the tumor bearing limb and were similar to changes seen with tumor growth. PCr was lost within 7 minutes, with concurrent increase in Pi and loss of NTP. Complete loss of all high energy phosphates occurred by 40 minutes of occlusion. In vivo tumor 31P NMR spectroscopy can be used to estimate tissue metabolic status and may be useful in non-invasive prediction of hypoxic cell fraction, reoxygenation, and radiation treatment response.

Animals↗
PubMed1987

Enhancement of radiation-induced normal tissue damage by a fibrosarcoma.

Normal tissue damage in the legs of mice was enhanced by the presence of a fibrosarcoma (FSa I) in the leg at the time of treatment with single doses of 30 to 70 Gy. Damage was assessed by measuring leg contracture 23 to 365 days after irradiation of 8 mm diameter tumors. Animals with and without tumors were treated with 1.0 mg misonidazole/g body weight 30 min before irradiation to ensure that the tumors did not recur and interfere with the assessment of contracture. The data suggest that in some cases, late damage may be enhanced by destructive effects of the tumor on the tumor bed.

Animals↗
PubMed1987

Effect of temperature on blood flow and hypoxic fraction in a murine fibrosarcoma.

The effect of hypo to hyperthermic temperatures on tumor blood flow and hypoxic cell fractions was studied in a murine fibrosarcoma transplanted in the hind leg of anesthetized mice. The blood flow to the tumor was assessed by the determination of the uptake of Thallium-201; the hypoxic cell fraction was estimated from cell survival curves derived from data based on lung colony assay. Over a temperature range of 18 degrees to 46 degrees C, the maximal blood flow occurred at 35 degrees C which was approximately two times greater than that at room temperature (24 degrees C) or at 39 degrees C. The hypoxic cell fraction at 35 degrees C was 11%, and was significantly less than that at 24 degrees C or at 39 degrees C. The hypoxic cell fractions at 24 degrees C and at 39 degrees C were 45% and 32%, respectively. These results suggest that the optimal radiation sensitivity of peripherally located tumors can be obtained by warming the tumors to temperatures where maximal blood flow and minimal hypoxic cell fraction occur.

Animals↗
PubMed1989

Effect of combination therapy of radiation and local administration of OK-432 on a murine fibrosarcoma.

The effects of a combination therapy of radiation and local administration of OK-432, which is one of BRMs (biological response modifiers), were studied using a radioresistant murine fibrosarcoma with weak immunogenicity. Fifty percent tumor control doses were 83.5 (79.6-87.4) Gy in animals given radiation alone and 64.3 (57.9-71.0) Gy in animals given OK-432 immediately after radiation, indicating that this biological response modifier can enhance the radiation dose effectiveness by a factor of 83.5/64.3, that is, 1.30. Histological observations of treated tumors showed that the combination therapy induced a marked infiltration with lymphocytes and prominent degeneration and necrosis of the tumor cells. Examination of subsets of the infiltrating lymphocytes using the monoclonal antibodies showed that Lyt-2 positive lymphocytes were more abundant in the group given the combination therapy than in the radiation alone group on day 5 (p greater than 0.05). Two days later, Lyt-1, Lyt-2, and L3T4 positive lymphocytes increased in the group given the combination therapy, whereas these lymphocytes disappeared in the group given radiation alone.

Animals↗
PubMed1991

Effect of environmental conditions (pH, oxygenation, and temperature) on misonidazole cytotoxicity and radiosensitization in vitro and in vivo in FSaIIC fibrosarcoma.

The effect of pH on misonidazole-induced cell killing at normal and elevated temperatures and on radiosensitization by misonidazole at 37 degrees C was assessed in FSaIIC fibrosarcoma cells in vitro. At doses of 5-500 microM for 1 hr, misonidazole was 1.5- to 2-fold more toxic toward hypoxic versus euoxic cells at 37 degrees C and pH 7.40. At 42 degrees C and 43 degrees C at pH 7.40, a less than 2-fold increase in cytotoxicity was observed in both normally oxic and hypoxic cells as compared with 37 degrees C. At pH 6.45 and 37 degrees C, misonidazole was less cytotoxic toward both euoxic and hypoxic cells than at pH 7.40. Unexpectedly, exposure to misonidazole at 42 degrees C or 43 degrees C and pH 6.45 caused no significant increase in cytotoxicity over that attributable to hyperthermia alone. Similarly, the dose modifying effect of misonidazole on single radiation fractions in vitro was also reduced at pH 6.45 versus pH 7.40 (2.60 versus 2.40, p less than 0.01). In vivo, treatment of the FSaIIC tumor with misonidazole (1 g/kg) and/or local hyperthermia (43 degrees C for 30 min to the tumor-bearing limb) in conjunction with radiation (10, 20, or 30 Gy) yielded a radiation dose modifying factor for misonidazole of 1.32, for hyperthermia of 1.38, and for the combination of 2.06 (probably additive). Analysis of the cytotoxicity achieved by these treatments in Hoechst 33342 dye-selected tumor subpopulations demonstrated that, whereas radiation was more toxic toward bright (presumably euoxic) cells, misonidazole, hyperthermia, and the combination were significantly more toxic toward dim (presumably hypoxic) cells. The addition of both hyperthermia and misonidazole to radiation more than overcame the relative resistance of the dim subpopulation to 10 Gy. These results indicate that misonidazole is a reasonable drug for use with hyperthermia and radiation to increase killing of hypoxic cells, but the decrease in cytotoxicity and radiosensitizing abilities of this agent observed under acidotic conditions could reduce the effectiveness of this treatment.

Animals↗
PubMed1991

The accelerated repopulation of a murine fibrosarcoma, FSA-II, during the fractionated irradiation and the linear-quadratic model.

Radiation response of a spontaneous mouse fibrosarcoma, FSa-II, to various fractionated doses was studied in vivo together with single dose cell survival curves. Early generation isotransplants were used. Animals were C3Hf/Sed mice derived from our defined flora mouse colony. Lung colony and TD50 assays were used to determine cell survival. Surviving fractions were determined following fractionated irradiations of 1.0 to 5.0 Gy each per fraction with interfractional time intervals of 4 hr. The alpha/beta ratio based on fractionated irradiations was 8.8 Gy for aerobic FSa-II tumor cells and flexure dose was less than 1.3 Gy. Multiple fractions of 5.0 Gy each given with 4, 12, and 24 hr intervals showed an increase in survival with increasing interfractional time interval, suggesting a rapid repopulation of tumor cells between fractions; namely, cell doubling time was shortened between fractions after the first 5.0 Gy doses. These results indicated that tumor cell repopulation is a critical factor in the fractionated radiotherapy. Linear-quadratic model was fitted to single dose survival data. Single dose survival curve of aerobic FSa-II tumor cells following lung colony assays which allowed determination of minimal survival of approximately 3.0 x 10(-3) showed that alpha, beta, and alpha/beta ratios were 0.25 Gy-1, 0.048 Gy-2, and 8.47 Gy, respectively. Single dose survival curve of the same aerobic cells determined by both lung colony and TD50 assays to a survival level of approximately 3.0 x 10(-6) demonstrated that alpha, beta, and alpha/beta ratios were 0.375, 0.0127, and 29.5, respectively. Similar determination for hypoxic FSa-II tumor cells showed that alpha, beta values were smaller whereas the alpha/beta ratio was much larger than for aerobic cells. The oxygen enhancement ratio calculated by the alpha/beta ratios was greater than 3.0.

Animals↗
PubMed1992

Potentiation of radiation response in human carcinoma cells in vitro and murine fibrosarcoma in vivo by topotecan, an inhibitor of DNA topoisomerase I.

DNA topoisomerase I, a nuclear enzyme important for solving topologic problems arising during DNA replication, has been identified as a principal target of a plant alkaloid, 20(s)-camptothecin. In view of the profound biochemical effects of camptothecin and its analogues on DNA replication and the differential cytotoxic effects on human tumors in xenografts, experiments were performed to determine whether topotecan, a camptothecin analogue, would potentiate the radiation effects on human carcinoma cells in culture and murine fibrosarcoma in mice. Cell culture studies showed that a dose dependent reduction in cell survival was obtained with a 4 hr exposure of the drug following irradiation of cells. No enhancement of cell killing was seen when cells were treated with the drug before irradiation. Preliminary in vivo tumor studies showed a significant radiosensitizing effect of topotecan that was both drug dose (20 mg/kg) and time sequence (4 hr before irradiation) dependent. There was no enhanced skin reaction following the combined treatments.

Animals↗
PubMed1993

Timing and sequence of hyperthermia in fractionated radiotherapy of a murine fibrosarcoma.

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.

Animals↗
PubMed1992

High-performance liquid chromatographic determination of navelbine in MO4 mouse fibrosarcoma cells and biological fluids.

A high-performance liquid chromatographic method is described for separating and determining navelbine and possible metabolites in plasma, cell culture medium and MO4 cells. Navelbine is extracted from these fluids by ion-pair extraction with sodium octylsulphate as the counter-ion at pH 3. The system uses a cyano column as the stationary phase and a mobile phase of acetonitrile-0.12 M phosphate buffer (pH 3) (60:40, v/v). Application of the method to a study of the pharmacokinetic behaviour of navelbine in MO4 mouse fibrosarcoma cells is reported.

Animals↗
PubMed1993

Muscarinic M3 receptors mediate total inositol phosphates accumulation in murine HSDM1C1 fibrosarcoma cells.

Muscarinic receptors in murine fibrosarcoma HSDM1C1 cells were characterized using both radioligand binding and total inositol phosphates accumulation (IPs). Muscarinic agonists elicited a concentration-dependent enhancement of IPs accumulation with a maximum of 14-fold stimulation above basal level. The following potencies (-log EC50) were observed for the full agonists: (+)-cis-dioxolane 5.4, oxotremorine-M 5.3, (+)-muscarine 5.2 and carbachol 5.0. Bethanechol (4.1) and arecoline (5.0) were partial agonists, evoking 43 and 55%, respectively of the maximum level of stimulation to (+)-cis-dioxolane, whereas pilocarpine and McN-A-343 were inactive as agonists (1 mumol/l-1 mmol/1). The apparent affinities for muscarinic antagonists (-log KB) estimated by Schild regression were: 4-DAMP (4-diphenylacetoxy-N-methylpiperidine methiodide) 9.2, dicyclomine 7.0, pirenzepine 6.9, (+/-)-p-F-HHSiD (para-fluoro-hexahydro-siladifenidol) 7.0, AF-DX 116 6.2, methoctramine 5.7. In saturation binding studies using [3H]N-methylscopolamine a homogeneous population of sites was identified, with a density of 145 pmol/mg protein. In competition radioligand binding studies, the following apparent affinities (-log Ki) were observed: 4-DAMP 9.7, dicyclomine 8.3, (+/-)-p-F-HHSiD 7.6, AF-DX 116 6.8, methoctramine 6.6 and gallamine 6.8. In binding studies all antagonists studied recognized a single population of sites, as judged by the Hill coefficients from the displacement isotherms. These data are consistent with HSDM1C1 cells expressing an apparent homogeneous muscarinic M3 population that mediates a large level of total IPs accumulation. This clonal line may provide a useful model to further elucidate relationship between endogenous muscarinic M3 receptor stimulation and IPs accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗