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Growth-related variations in the glycosaminoglycan synthesis of ultraviolet light-induced murine cutaneous fibrosarcoma cells.

Glycosaminoglycan synthesis was studied in cell populations of ultraviolet light-induced murine cutaneous fibrosarcoma cells under conditions of varying growth rates in vitro. After labeling with the precursors, 3H-glucosamine and 35SO4, sulfated glycosaminoglycans recoverable by direct proteolysis of the culture monolayers increased approximately 5-fold on a per cell basis from sparsely populated, exponential cell cultures (greater than 85% of cells in S, G2, or M phases) to stationary cultures inhibited by high cell density (greater than 50% of cells in G1). Within this cell surface-associated material, the relative ratio of heparan sulfate to the chondroitin sulfates was approximately 60/40% under conditions of exponential growth; in the growth-arrested cultures, the reverse ratio was found. The substratum attached material, obtained from the flask surface after ethyl glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA)-mediated detachment of the monolayers, contained relatively more hyaluronic acid, heparan sulfate, and chondroitin sulfates in the most actively proliferating cultures compared with the growth-inhibited cell populations. Furthermore, heparan sulfate and the chondroitin sulfates, which were enriched in the substratum material and in the cell pellet of exponential cultures, showed a relative shift to the cell surface-associated compartment (releasable by mild trypsinization after EGTA-mediated cell detachment) and to the compartment loosely associated with the pericellular matrix (i.e., released into the supernatant during detachment of the monolayers in the presence of EGTA). These results demonstrate that a variety of differences in the quantities, relative compositional ratios, and cell compartment distributions of hyaluronic acid and sulfated glycosaminoglycans occur in fibrosarcoma cell populations which vary in their rate of cell growth consequent to cell density in culture.

Animals↗

Arachidonic acid metabolism in murine fibrosarcoma cells with differing in vivo and in vitro characteristics.

Arachidonic acid metabolism was examined in a series of strongly malignant murine fibrosarcoma cell lines and in a series of weakly malignant lines isolated from the same tumors. The cells were examined in the unstimulated state and after stimulation with 12-O-tetradecanoyl phorbol acetate (TPA), laminin or fibronectin. All 3 agents were known from previous studies to induce adherence and motility in the murine fibrosarcoma cells. When the cells were prelabelled with 3H-arachidonic acid, all 3 agents stimulated the release of radioactivity into the supernatant fluids. The response to TPA was rapid while the response was slower but sustained when either laminin or fibronectin was used as the stimulating agent. This is of interest because TPA induces a rapid but transient adherence response in the same cells while laminin and fibronectin induce a slow, sustained response. Examination by radioimmunoassay procedures indicated that both control cells and stimulated cells were able to produce a variety of lipoxygenase and cyclooxygenase metabolites. In quantitative terms, the strongly malignant cells were more active than their weakly malignant counterparts. They released greater amounts of radioactivity into the supernatant fluid and produced a greater quantity of arachidonic acid metabolites, particularly prostaglandin E2, than did the corresponding weakly malignant cells. This is of interest because previous studies have shown that while both the strongly and weakly malignant cells respond in the adherence assay to TPA, laminin and fibronectin, only the strongly malignant cells demonstrate directional motility (chemotaxis and haptotaxis).

Animals↗

Deficits in elevating membrane potential of rat fibrosarcoma cells after cell contact.

Most cancer cells are known to have lower resting cellular potentials than do their normal counterparts. This study investigates how these potentials establish themselves during growth and cellular contact in tissue culture. Normal quail embryonic fibroblasts and quail fibrosarcoma (QT-35) and normal rat kidney cells and rat fibrosarcoma (from rat fibroblasts chemically transformed by nitroquinoline oxide) were recorded intracellularly using high-impedance micropipets. In high-density high-contact cultures, both quail and rat cancer cells had lower potentials than did normal cells (-20.7 compared to -40.1 mV for quail and -30.7 compared to -61.9 mV for rat). In low-density mitotically synchronous cultures, the rat cells were recorded every 4 hr for 96 hr. Starting at a low density, normal cell membrane potential is maintained at a low level through subsequent cell divisions. Without any additional change in cell density, the potential suddenly elevates to a high level. The membrane potential of cancer cells is by contrast unrelated either to cell density or to time. Cancer cells maintained an intermediate potential from low to very high densities and never elevated their potential to high values. The failure of cancer cells to reach high potentials may be linked to their uncontrolled cell division.

Animals↗

Infantile fibrosarcoma: report of cases.

Infantile "fibrosarcoma" occurred in a newborn male infant and in a 2-month-old female infant. In both cases, the tumors grew rapidly and showed the histological features of malignancy. However, they were treated successfully with simple resections. Review of the literature shows that infantile fibrosarcoma has a relatively favorable prognosis. Simple local excision is the initial treatment of choice for lesions occurring in infants and children less than 5 years old.

Female↗

[Clinico-morphological analysis of bone fibrosarcomas (a retrospective study)].

The data on 35 cases of bone fibrosarcoma treated at the Center clinic in 1955-1982 are presented. A retrospective morphological investigation left diagnosis unchanged in 17 cases (48.6%). In 9 cases diagnosis was changed to fibrous histiocytoma of the bone, in 2--parostal sarcoma and in one case--"dedifferentiated" chondrosarcoma. In 6 cases, diagnosis could not be improved and neoplasms were identified as poly-morphocellular sarcoma. Clinically, a more favorable course and prognosis are distinguishing features of fibrosarcoma as compared with osteogenic sarcoma and malignant fibrous histiocytoma.

Adolescent↗

[Fibrosarcoma of bone].

The authors have treated forty-five cases of fibrosarcoma of bone between 1949 and 1979. Tumours with chondrogenesis or osteogenesis to any extent have been excluded from the study. The conclusions are that fibrosarcoma represent 10 p. 100 of all bone tumours. Microscopy was difficult and in some cases it was not easy to determine both the fibroblastic origin and the presence of malignancy. Eight per cent of the tumours were primary and 20 p. 100 secondary. The global results indicated 40 p. 100 survival after five years. Twenty-four cases were treated by amputation of which twenty-two were followed up and fifteen were alive after five years. In nine cases, resection was performed. Recurrence occurred in five cases, three of which had to be amputated of which two survived. Two others were treated by irradiation without success. Ten cases were treated primarily by irradiation of which only three survived after heavy dosage. Proximally situated tumours had a very poor prognosis with no survival. The prognosis appeared to be better in those under forty years of age (55 p. 100 survival) than over forty years (11 p. 100 survival).

Adolescent↗

Production of immunosuppressive factor(s) by a weakly immunogenic fibrosarcoma T 241.

Earlier we have reported that the progressive growth of Lewis fibrosarcoma T241 in C57 BL/6J mice causes immunosuppression. Tumor-bearing mice were shown to possess suppressor T cells in the spleen and soluble immunosuppressive factors in the serum. The present study investigated the effect of supernatants from T241 cultures on the response of normal spleen cells to mitogens and antigens. When added to the cultures at time zero, these supernatants inhibited the proliferation responses induced with concanavalin A and phytohemagglutinin. The responses to allo-antigens in mixed lymphocyte cultures and cell-mediated lympholysis were also significantly suppressed (P less than 001). Each of these responses was suppressed in a dose-dependent manner. Predominantly associated with material possessing molecular weight of less than 10,000 daltons, the suppressive activity was completely lost by heating supernatants at 80 degrees C for 30 min. Thus, the presence of immunosuppressive materials in the culture fluids of T241 together with the occurrence of suppressor T cells and the humoral immuno-suppressive factor(s) in tumor-bearing mice are suggestive of a multifactorial mechanism whereby the growth of fibrosarcoma T241 causes immunodepression in the host.

Animals↗

Inhibition by bovine endothelial cells of degradation by HT-1080 fibrosarcoma cells of extracellular matrix proteins.

Medium conditioned by bovine arterial endothelial cells inhibited the degradation by human fibrosarcoma cells of living cultures of rat smooth muscle cells or their cell-free extracellular matrices. Endothelial cell-conditioned medium had no effect on the growth kinetics of fibrosarcoma cells, and the inhibitory influence of conditioned medium on matrix degradation was greatest with low numbers of tumor cells. Conditioned medium inhibited the production of tumor cell plasminogen activators, enzymes previously found to play a role in matrix glycoprotein degradation. The endothelial factor was heat- and acid-stable and non-dialyzable, and mixing experiments showed that it did not directly inactivate the tumor cell plasminogen activator. Endothelial cells may therefore modulate the production of proteolytic enzymes important in the implantation stage of tumor metastasis.

Animals↗

[Glioblastoma and fibrosarcoma in the brain with metaplastic bone formation--a case report].

The authors report a case in which left deep temporal fibrosarcoma with calcified area developed about 6 months after radiation therapy for left temporal astrocytoma. A 37 year-old woman was admitted to our clinic because of headache and visual deterioration. CT scan and angiography suggested left deep temporal glioma and on August 5, 1980, partial resection was performed. Histological sections showed astrocytoma G 2. Postoperative course was uneventful and she left the hospital after radiation therapy of 50 Gy. On March, 1981, right hemiparesis was noticed and progressed rapidly. CT scan suggested left temporal tumor recurred. On March 30, 1981, second operation was performed and this time, histological sections showed glioblastoma. After operation, beta-Interferon (IFN) was given intratumorally via Ommaya's reservoir (3 X 10(6) IU, daily). But in spite of IFN therapy, tumor became larger and she died on June 30, 1981. Autopsy revealed coexistence of glioblastoma and fibrosarcoma with metaplastic bone formation. A brief discussion concerning the problem of cerebral mixed tumors follows the description of the case.

Adult↗

Enhanced experimental metastasis of ultraviolet light-induced fibrosarcomas in ultraviolet light-irradiated syngeneic mice.

Some ultraviolet light (UV)-induced fibrosarcomas produce more experimental pulmonary tumor colonies in UV-irradiated hosts than in normal syngeneic recipients. The number of experimental metastases produced following i.v. injection of these tumors increases in proportion to the dose of UV radiation. This enhancement can be transferred with lymphoid cells to lethally X-irradiated recipients and with partially purified T-lymphocytes to untreated syngeneic mice. Some UV-induced fibrosarcomas do not form experimental metastases readily, even in UV-irradiated recipients, suggesting that both immunological and nonimmunological factors are important in limiting metastasis formation.

Animals↗

Rapid phenotype variation in cells derived from lung metastases of KHT fibrosarcoma.

We have established previously that intravenously derived metastatic variants are generated in KHT fibrosarcoma cells at an effective rate of 10(-5)/cell/generation. To study the properties of these variants further, we examined several lines of KHT fibrosarcoma cells obtained from experimental lung metastases. When tested using an experimental metastasis assay, some of the lines were highly metastatic, relative to parental lines, but these highly metastatic phenotypes were often rapidly lost as the lines were grown in vitro, and both decreases and increases in metastatic ability were observed. In another set of experiments, lines obtained by 10 serial selections of experimental lung metastases without intervening in vitro growth between passages were also analyzed. Again, while highly metastatic phenotypes were observed in some instances, they did not persist beyond 1 or 2 in vivo passages, and the series as a whole failed to reveal a persistent increase in ability to form experimental metastases. We conclude from these experiments that although metastatic variants are generated at high rates in KHT cell lines, the phenotype is lost at even higher rates, and metastatic variants represent only a small proportion of the tumor cell population. Thus, it appears that in this system rapid phenotypic variation may play an important role in the metastatic process.

Animals↗

Primary central (medullary) fibrosarcoma of bone.

Eighty cases of primary fibrosarcoma of bone from the Rizzoli Institute are reviewed. There was a slight male predominance with a wide patient age distribution. Roentgenologically, low grade fibrosarcomas had generally well-defined margins and a "soap-bubble" appearance. High grade tumors appeared permeative and more aggressive. Histologically, the majority of tumors were high grade (3 and 4). Prognosis correlated well with the grade of the tumor. The 10-year survival rate was 83% for low grade sarcomas and 34% for high grade tumors. Local recurrence was a bad prognostic sign.

Adolescent↗

Identification and partial characterization of a low-molecular-weight inhibitor of leukotaxis from fibrosarcoma cells.

Lysate from T-241 murine fibrosarcoma cells contains a low-molecular-weight (Mr less than 1000), heat-stable peptide factor which has antichemotactic activity for both macrophages and polymorphonuclear leukocytes in vitro. The tumor factor was partially purified from an alcohol extract of the fibrosarcomas by gel filtration, anion exchange chromatography, and paper chromatography successively. This factor inhibits both the hydrolytic cleavage of the peptide attractant N-formylmethionylleucylphenylalanine by polymorphonuclear leukocytes and the methylation of both protein carboxyl groups and membrane phospholipids. Furthermore, the factor does not appear to compete with N-formylmethionylleucylphenylalanine for its receptor. The tumor-derived material, therefore, affects biochemical reactions believed to have roles in the expression of an adequate leukotactic response. These data suggest that depressed inflammatory responses at sites of neoplasms may result in part from release of small, potent inhibitors of leukotaxis from tumors themselves.

Animals↗

Fibrosarcoma of ovary. A new component in the nevoid basal-cell carcinoma syndrome.

An 8-year-old child with nevoid basal-cell carcinoma syndrome who developed abdominal pain underwent exploratory laparotomy. Both ovaries were enlarged and replaced by fibroblastic proliferations having cellular foci with high mitotic indices (greater than 4 mitoses/10 high-power fields) diagnostic of fibrosarcoma. Two years following salpingo-oophorectomy, a metastasis was excised from one adnexa. Further recurrence or distant metastasis was not evident after 6 more years of follow-up. The association of fibrosarcoma of the ovary in a patient with nevoid basal-cell carcinoma further expands the multifarious nature of this syndrome.

Adnexa Uteri↗

[Meningeal fibrosarcomas].

The authors present 4 operated cases of primary fibro sarcomas of the dura mater. Only, a few number of cases had been described in the literature. In Zulch's classification (1957) of 6000 brain tumors, there were 162 cases of sarcoma (i.e. 2,7%) and among sarcoma, 30 cases of fibrosarcoma of the dura mater. In according with the WHO classification of brain tumors (Zulch, 1979), the primary fibrosarcoma of the dura mater takes place in the group of meningeal sarcomas with the polymorphic cell sarcoma and the primary meningeal sarcomatosis. The pre-operative diagnosis is difficult, because neither clinical data, neither neuroradiological findings are characteristics. The prognosis of the patients with this tumor is poor, however some examples are known to have had a long post-operative survival. The association: complete surgical extirpation--post-operative radiation appears like to best treatment. Pathological examination showed in our four tumours, the features of fibroblastic sarcomas with haemorrhagic zones and foci of osteoid metaplasia. The ultra-structural study in 2 cases, confirmed the specificity of tumoral cells which did not display any histological similarity to the arachnoïdal cells. In one case, a myofibroblastic differentiation was evident, and thus, confirmed the plasticity of tumoral fibroblastic cells. The immuno-histochemical reaction of GFAP revealed reactive astrocytic areas in one case inside the immuno-histochemical sarcomatous tissue.

Aged↗

Kinetic heterogeneity in density-separated murine fibrosarcoma subpopulations.

Murine fibrosarcoma cells can be separated into subpopulations by centrifugation through 10 to 35% Renografin density gradients. Previous work has shown that the heavier cell populations are rich in chronically hypoxic cells. In this study, each subpopulation was characterized for thymidine incorporation, thymidine transport, thymidine triphosphate pool sizes, and thymidine triphosphate specific activities. The heavier cell populations have less accessibility to exogenous thymidine, and they have lower endogenous pools of thymidine triphosphate and synthesize lower levels of DNA than do the lighter cell populations. However, if the cells are removed from the tumors and labeled with [3H]thymidine in vitro, all subpopulations synthesize DNA at similar rates. Two-parameter flow cytometry using acridine orange staining following partial acid denaturation of chromatin identified a small quiescent population in the most dense cell fraction, but the small number of these cells cannot account for the results of the biochemical studies. It appears that the hypoxic cells in the fibrosarcoma tumors are noncycling or slowly cycling, are in all phases of the cell cycle, and recover their ability to synthesize DNA when cultured under in vitro conditions.

Animals↗

Enhanced metastatic potential of murine fibrosarcomas treated in vitro with ultraviolet radiation.

The purpose of this study was to determine whether repeated treatment of tumor cells in vitro with mutagenic doses of ultraviolet (UV) radiation could influence the metastatic behavior of these cells in vivo. Three cloned lines of UV-2237, a fibrosarcoma induced in a C3H- mouse by chronic irradiation with UV, and SF-19, a spontaneous C3H- fibrosarcoma, were grown in culture. These cell lines varied from low to high metastatic potential as determined by in vivo tests. The cultures were exposed to UV radiation from an FS40 sunlamp at a dose that killed 40% of the cells. These UV radiation exposures were repeated at 3- to 5-day intervals for a total of 5 treatments. The mutation frequency was analyzed by monitoring the appearance of ouabain-resistant colonies following UV irradiation. With all four tumor lines, the frequency of conversion to ouabain resistance was increased more than 10-fold. Tumor cells given 5 UV radiation treatments and control cultures carried in parallel without exposure to UV radiation were tested for metastatic potential in an in vivo lung colony assay. Cell lines treated in vitro with UV radiation produced more experimental metastases than the counterpart unirradiated cultures. We conclude that, in all four tumor lines, exposure of tumorigenic cells to mutagenic doses of UV radiation can alter their biological behavior and that this may contribute to the progression of tumors from low to high metastatic capability.

Animals↗

A primary fibrosarcoma of the liver.

Primary sarcomas of the liver are extremely rare tumours, the majority being classified as angiosarcomas. To our knowledge, only seven cases of fibrosarcomas have been reported. Therefore it is of considerable importance and interest to add yet another case of this nature. The diagnosis of primary hepatic fibrosarcoma was verified during explorative surgery and subsequently autopsy. It is stressed that there are no special clinical features and the diagnosis is practically always made during exploratory laparotomy, or at autopsy.

Adult↗